Clinical Sources for Helix Anesthesia

Compiled and maintained by Anastasia Jackson, DNAP, CRNA — Certified Registered Nurse Anesthetist · Last updated September 28, 2026

Every dose, max, and protocol in Helix Anesthesia mapped to its primary reference. This document maps each clinical value in the app to a verifiable external source (FDA package insert, society guideline, or primary literature) so any clinician can verify our work.

Review status — awaiting independent clinical review. The doses and protocols below were compiled by the author, a practicing CRNA, and cross-referenced against the cited sources. Independent clinical review by anesthesia clinicians other than the author has not yet been completed. Reviewers who complete a review are listed in the Reviewer Audit Log at the bottom of this document. Until that log shows a signature for a given section, treat that section as author-cited and independently verifiable — every value links to its primary source above — but not independently reviewed.

"Independent clinical review" is used deliberately in place of "peer review." Peer review is a term of art for the process journals apply to manuscripts, and this document has not been through it. What is described here is a source-verification and clinical-judgment audit of the app's content, which is a different and narrower thing.

Disclaimer: Doses verified to the best of authors' knowledge against the cited references at the time of authoring. Drug labels change; verify each dose against the most current package insert before clinical use. Helix Anesthesia is a reference tool and does not replace clinical judgment.

How to find any cited source

FDA package inserts — All major drug PIs are searchable at the FDA's DailyMed:

• https://dailymed.nlm.nih.gov/dailymed/index.cfm
• Direct PDFs hosted at accessdata.fda.gov are linked inline below.

Journal articles — Every cited article can be located on PubMed by entering the citation (author + year + journal):

• PubMed search: https://pubmed.ncbi.nlm.nih.gov/
• Free abstracts for every cited article; full text may require institutional access via your hospital library.
• Many articles are also open-access on PubMed Central (PMC).

Society guidelines — Direct URLs to society documents are listed inline (AHA, ASA, ASRA, ACOG, SMFM, MHAUS, NCCMERP).

Textbook references — Edition-dependent page numbers. Chapter titles are the stable reference. Publisher URLs for textbooks:

• Miller's Anesthesia, 10th ed (Gropper, Cohen, Eriksson, Fleisher, Leslie, Johnson-Akeju; Elsevier 2024; ISBN 9780323935920): https://shop.elsevier.com/books/millers-anesthesia-2-volume-set/gropper/978-0-323-93592-0 · Also on ClinicalKey
• A Practice of Anesthesia for Infants and Children, 6th ed (Coté, Lerman, Anderson; Elsevier 2018; ISBN 9780323429740): https://shop.elsevier.com/books/a-practice-of-anesthesia-for-infants-and-children/cote/978-0-323-42974-0
• Stoelting's Pharmacology & Physiology in Anesthetic Practice, 6th ed (Flood, Rathmell, Urman; LWW 2022; ISBN 9781975126896): https://shop.lww.com/Stoelting-s-Pharmacology---Physiology-in-Anesthetic-Practice/p/9781975126896
• Cousins and Bridenbaugh's Neural Blockade, 4th ed (Cousins, Carr, Horlocker, Bridenbaugh; LWW 2009): https://www.wolterskluwer.com/en/solutions/ovid/cousins-and-bridenbaughs-neural-blockade-in-clinical-anesthesia-and-pain-medicine-5380
• Barash, Cullen, and Stoelting's Clinical Anesthesia, 9th ed (Cullen, Stock, Ortega; LWW 2023; ISBN 9781975199074): https://shop.lww.com/Barash--Cullen--and-Stoelting-s-Clinical-Anesthesia--Print---eBook-with-Multimedia/p/9781975199074

1. Local Anesthetics — Maximum Doses

The figures below are absolute single-dose ceilings intended for LAST (local anesthetic systemic toxicity) calculation — i.e., the maximum a patient should receive in one administration regardless of technique (infiltration, peripheral block, epidural). Where the FDA label gives an explicit mg/kg, that is quoted directly. Where the FDA label only gives an absolute mg cap (bupivacaine, mepivacaine adult, ropivacaine), the mg/kg figure is the standard textbook back-calculation used across Miller's, Stoelting's, and Barash. Infiltration-only tables in some textbooks (e.g. Miller's 8e Table 36-4) quote more conservative numbers for that specific use — those are not wrong, but they are narrower than the toxicity-ceiling values below.

Primary URLs:

• Marcaine (bupivacaine HCl) PI — DailyMed
• Xylocaine (lidocaine HCl) PI — DailyMed
• Naropin (ropivacaine) PI — DailyMed
• Nesacaine (chloroprocaine) PI — DailyMed
• Carbocaine (mepivacaine) PI — DailyMed
• Novocaine (procaine) PI — DailyMed
• Citanest (prilocaine) PI — DailyMed
• Pontocaine (tetracaine) PI — DailyMed
• Miller's Anesthesia 10e Ch. 47 "Local Anesthetics" — Elsevier
• ASRA LAST Checklist (max-dose guidance) — ASRA

2. Sugammadex (Reversal)

URLs:

• Bridion (sugammadex) PI — DailyMed search · FDA 2015 label PDF
• FDA approval letter — FDA NDA 022225

Caveats noted in app:

• Hormonal contraceptive interaction (PI Section 7.1)
• CrCl <30 mL/min not recommended (PI Section 8.6)
• Bradycardia rare but reported (PI Section 5.2)

3. Sugammadex — Pediatric

Pediatric dosing extrapolated from adult PI per Bridion label (approved age ≥ 2 years by FDA 2021) — DailyMed Bridion label.

4. Neuraxial / Intrathecal Adjuvants

Epidural adjuvants:

5. Peripheral Block Adjuvants

6. Spinal Anesthesia Dose by Procedure

Alternative LAs (Spinal screen):

• Ropivacaine 0.5–0.75%: 12–20 mg (Naropin PI off-label spinal use) — DailyMed
• Mepivacaine 2% isobaric: 40–60 mg (the 1.5% dilution is hypobaric — see 6c) — Dose-response study: Zayas VM, et al. Anesth Analg 1999;89:1167-1171 — PubMed
• 2-Chloroprocaine 3% PF: 30–50 mg — Goldblum E, Atchabahian A. Acta Anaesthesiol Scand 2013 — PubMed; Nesacaine PI — DailyMed
• Lidocaine 5% hyperbaric: 60–100 mg (⚠ TNS rate 10-30% — Pollock JE. Anesth Analg 2003) — PubMed; Xylocaine PI — DailyMed
• Tetracaine 0.5–1%: 6–12 mg — Pontocaine PI — DailyMed

6b. Epidural Dosing — Surgical, Cesarean and Labor

Converting an epidural to surgical anesthesia. Give 15–20 mL in 5 mL increments to T4.

Bicarbonate is 1 mEq per 10 mL of lidocaine, freshly mixed. Fentanyl 50–100 mcg improves block quality. Epidural morphine 3 mg after delivery for postoperative analgesia.

Chloroprocaine and subsequent opioid. 3% 2-chloroprocaine antagonizes epidural opioids and amide local anesthetics given after it: faster sensory regression, higher intravenous PCA morphine use at 4 and 24 hours, and higher pain scores at 1 and 2 hours. The gap falls between chloroprocaine regressing at 30–45 minutes and epidural morphine reaching peak effect. Source: Post-cesarean Analgesia With Epidural Morphine Following Epidural 2-chloroprocaine — ClinicalTrials.gov NCT04369950.

Postoperative epidural infusion (thoracic or abdominal surgery):

Bupivacaine 0.2% brings more intraoperative vasopressor use and more temporary neurologic complications with no added benefit — Anaesthesia 1999 — PubMed. A lumbar catheter needs roughly 25% more volume than a thoracic one for equivalent analgesia (6.4 vs 5.1 mL/h), so the catheter belongs at the dermatome of the incision.

Labor epidural maintenance:

Dural puncture epidural gives faster onset, greater sacral spread and fewer asymmetric blocks than a standard epidural, without the intrathecal opioid side effects of a combined spinal-epidural. A systematic review of five randomized trials concluded the efficacy is not yet definitively established. Source: Chau A, et al. Anesth Analg 2017 — PubMed.

The PCEA row is the one parameter set above that reflects published practice rather than a dose-finding trial, and is marked as such rather than presented as evidence.

6c. Baricity of Spinal Solutions

The diluent decides, not the concentration. Dextrose added is hyperbaric, plain is isobaric, sterile water is hypobaric. The same 0.5% bupivacaine mixed with 10% dextrose, 0.9% saline or distilled water and given as 7.5 mg to supine patients reached T4, T11 and L1 respectively — seven dermatomes from the diluent alone.

Tetracaine depends entirely on the diluent. The 1% solution is isobaric as supplied. Mixed 1:1 with 10% dextrose it becomes the hyperbaric 0.5% in 5% dextrose; the powder dissolved in sterile water gives a hypobaric 0.1%.

Adding fentanyl makes an isobaric solution hypobaric. Pure fentanyl is 0.99360 g/mL, and every isobaric local anesthetic mixed with it measured below the lower 99% confidence limit of CSF density. Adding fentanyl to a hyperbaric solution does not make it isobaric. Source: Jasinski T, et al. Pharmaceuticals 2021 — DOI.

"Isobaric" means dextrose-free, not density-matched. Measured at body temperature, every commercially prepared plain solution is less dense than the normal CSF range, which is why plain solutions spread less predictably than hyperbaric ones. CSF at 37°C has a mean density of 1.0003 g/mL and is least dense in pregnancy, most dense in men — so plain ropivacaine, sitting just 0.00026 from the lower limit of the CSF confidence interval, may behave hypobarically in men. Sources: Horlocker TT, Wedel DJ. Anesth Analg 1993 — PubMed; Br J Anaesth 2004;92(4):547 — PubMed.

Intrathecal ropivacaine is not FDA-labeled in the United States, and intrathecal chloroprocaine in the US is off-label, supported by published practice.

7. Sevoflurane / Volatile Anesthetics — (MAC values)

MAC values per age group from:

• Stevens WC, et al. Anesthesiology 1975;42:197-200 (original MAC isoflurane study; commonly referenced for sevoflurane via comparator data) — PubMed
• Mapleson WW. Br J Anaesth 1996;76:179-185 (age-adjustment formula for MAC) — PubMed
• Ultane (sevoflurane) PI — DailyMed · FDA 2006 label PDF; the current label (AbbVie, February 2025) — DailyMed — for the blood:gas range of 0.63–0.69, compound A formation in CO₂ absorbent, and the toxic gases a desiccated absorbent can produce
• Forane (isoflurane) PI — DailyMed
• Suprane (desflurane) PI — DailyMed
• Stoelting's Pharmacology 6e — LWW; Miller's 10e — Miller's; Barash 9e — LWW. Where the sources differ, the app shows both: on chronic ethanol, Stoelting gives no change in MAC and Barash an increase; Stoelting gives MAC-awake as about 0.5 × MAC and Barash approximates MAC-BAR at 1.5 × MAC, each shown beside the measured figure below
• Lerman J, Sikich N, Kleinman S, Yentis S. The pharmacology of sevoflurane in infants and children. Anesthesiology 1994;80(4):814-824 — PubMed; Taylor RH, Lerman J. Minimum alveolar concentration of desflurane and hemodynamic responses in neonates, infants, and children. Anesthesiology 1991;75(6):975-979 — PubMed. The measured MAC values for neonates, infants and children
• Katoh T, Suguro Y, Ikeda T, et al. Influence of age on awakening concentrations of sevoflurane and isoflurane. Anesth Analg 1993;76(2):348-352 — PubMed. MAC-awake at about 0.34 × MAC for sevoflurane and isoflurane
• Daniel M, Weiskopf RB, Noorani M, Eger EI 2nd. Fentanyl augments the blockade of the sympathetic response to incision (MAC-BAR) produced by desflurane and isoflurane: desflurane and isoflurane MAC-BAR without and with fentanyl. Anesthesiology 1998;88(1):43-49 — DOI. MAC-BAR at about 1.3 × MAC for desflurane or isoflurane with 60% N₂O

8. Pediatric Doses

Emergency / Code

Primary reference for this entire section: AHA PALS 2020 — Topjian AA, et al. Circulation 2020;142:S469-S523 — AHA Journals · PubMed · ECC guidelines portal: cpr.heart.org.

Premedication

Induction Agents

Paralytics & Reversal

Analgesia & Opioid Reversal

Antiemetics

Cardiovascular

Local Anesthetics (Pediatric)

Smooth Emergence

MH — Dantrolene

8b. Maintenance Fluids — the 4-2-1 Rule

Primary: Holliday MA, Segar WE. The maintenance need for water in parenteral fluid therapy. Pediatrics 1957;19:823-832.

• PubMed

The app's maintenance rate is the Holliday-Segar calculation stated verbatim from this paper: 4 mL/kg/hr for the first 10 kg, 2 mL/kg/hr for the next 10 kg, 1 mL/kg/hr for each kg above 20. The hourly "4-2-1" form is the standard restatement of the paper's original 100/50/20 mL/kg/day figures; the two are the same numbers expressed per hour rather than per day. NPO deficit is that maintenance rate multiplied by hours fasted.

8c. Obturator Nerve Block

Technique — proximal interfascial: Taha AM. Ultrasound-guided obturator nerve block: a proximal interfascial technique. Anesth Analg 2012;114:236-239.

• PubMed

Anatomy and updated techniques: Yoshida T, Nakamoto T, Kamibayashi T. Ultrasound-Guided Obturator Nerve Block: A Focused Review on Anatomy and Updated Techniques. Biomed Res Int 2017;2017:7023750.

• PubMed

These two back the obturator block's anatomy and approach description. Local anesthetic volumes and maxima for this block follow the same ceilings as §1 and the block dosing engine, not these papers.

9. Apfel PONV Score

Primary: Apfel CC, Läärä E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology 1999;91:693-700.

• PubMed

Antiemetic doses cited in app:

• Ondansetron 4 mg IV — Zofran PI — DailyMed
• Dexamethasone 4-8 mg IV — Apfel CC, et al. NEJM 2004;350:2441-2451 (IMPACT trial) — PubMed; Decadron PI — DailyMed
• Droperidol 0.625-1.25 mg IV — Inapsine PI (FDA black box QT — monitor) — DailyMed
• Aprepitant 40 mg PO — Emend PI — DailyMed
• Scopolamine 1.5 mg transdermal — Transderm Scop PI — DailyMed

10. RCRI (Lee) + Gupta MICA

RCRI: Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999;100:1043-1049.

• URL: https://www.ahajournals.org/doi/10.1161/01.CIR.100.10.1043

Gupta MICA: Gupta PK, Gupta H, Sundaram A, et al. Development and validation of a risk calculator for prediction of cardiac risk after surgery. Circulation 2011;124:381-387.

• URL: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.110.015701
• NSQIP risk calculator (live tool): https://riskcalculator.facs.org/RiskCalculator/

The Gupta MICA coefficients used in the app are from the supplement of the Gupta 2011 Circulation paper.

11. STOP-BANG

Primary: Chung F, Yegneswaran B, Liao P, et al. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology 2008;108:812-821.

• URL (PubMed): https://pubmed.ncbi.nlm.nih.gov/18431116/
• STOP-Bang official site (additional content): http://www.stopbang.ca/

12. NPO Fasting Guidelines

Primary: ASA Task Force on Preoperative Fasting. Practice Guidelines for Preoperative Fasting and the Use of Pharmacologic Agents to Reduce the Risk of Pulmonary Aspiration: Application to Healthy Patients Undergoing Elective Procedures: An Updated Report. Anesthesiology 2017;126:376-393.

• URL: https://doi.org/10.1097/ALN.0000000000001452
• ASA Clear Liquids Update 2023 (extends to 2 hr): https://www.asahq.org/standards-and-practice-parameters
• Chewing gum: the 2023 ASA guideline suggests not delaying an elective case in healthy adults who are chewing gum, and confirming the gum has been removed before any anesthetic.
• Gum, hard candy, nicotine, smoking, obesity and pregnancy not in labor: Smith I, Kranke P, Murat I, et al. Perioperative fasting in adults and children: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2011;28(8):556-569 — PubMed.
• GLP-1 receptor agonists: Kindel TL, Wang AY, Wadhwa A, et al. Multi-society clinical practice guidance. Surg Endosc 2025;39(1):180-183 — PubMed; the ASA consensus-based guidance of June 2023; Oprea AD, et al. SPAQI consensus statement. Br J Anaesth 2025;135(1):48-78 — PubMed; Hocking SL, et al. 2025 ADS/ANZCA/GESA/NACOS recommendations. Anaesth Intensive Care 2025;53(5):300-306 — PubMed.
• The 2023 update in full, cited by the surgical case library: Joshi GP, Abdelmalak BB, Weigel WA, et al. 2023 American Society of Anesthesiologists Practice Guidelines for Preoperative Fasting: Carbohydrate-containing Clear Liquids with or without Protein, Chewing Gum, and Pediatric Fasting Duration. Anesthesiology 2023;138(2):132-151. https://doi.org/10.1097/ALN.0000000000004381
• Diabetes medications on the day of surgery: American Diabetes Association Professional Practice Committee for Diabetes. 16. Diabetes Care in the Hospital: Standards of Care in Diabetes—2026. Diabetes Care 2026;49(Suppl 1):S339-S355 — DOI, for holding oral glucose-lowering agents including metformin and for the basal insulin reductions. Thompson A, Fleischmann KE, Smilowitz NR, et al. 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM guideline for perioperative cardiovascular management for noncardiac surgery. J Am Coll Cardiol 2024;84(19):1869-1969 — DOI, for continuing metformin as reasonable (the two disagree), the SGLT2 inhibitor hold intervals, aspirin, and ACE inhibitors and ARBs.
• H2 blockers and proton pump inhibitors for obesity and reflux: the ASA 2017 guideline above, which rates them as may be used but not routinely, and the European guideline (2011). When they are used: Stoelting's Pharmacology 6e — LWW, for famotidine timing and dose; Barash 9e — LWW, for two-dose proton pump inhibitor timing. Miller's 10e — Miller's is also among the sources the app cites for fasting.

13. ASRA Anticoagulation

Primary: Kopp SL, et al. Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Fifth Edition). Reg Anesth Pain Med 2025. doi:10.1136/rapm-2024-105766.

• URL: https://rapm.bmj.com/content/early/2025/01/09/rapm-2024-105766

Every hold interval, restart interval and monitoring interval in the app's anticoagulation tables is taken from the fifth edition, including the guideline's own Remarks: annotations recording what changed from the fourth.

These rows carry values the guideline does not supply, and say so in the row itself:

Superseded, retained for reference: Horlocker TT, Vandermeuelen E, Kopp SL, Gogarten W, Leffert LR, Benzon HT. ASRA Evidence-Based Guidelines (Fourth Edition). Reg Anesth Pain Med 2018;43:263-309 — rapm.bmj.com. Where the two editions agree, the fifth is cited.

14. Crisis Checklists

15. OB Emergencies

16. Infusion Drug Concentrations

Final infusion concentrations and standard mixing instructions reference:

• Institute for Safe Medication Practices (ISMP) Standard Concentrations of Adult Continuous IV Infusions — ISMP
• Hospital pharmacy formulary standard concentrations (institution-specific)
• Stoelting's Pharmacology, 6th ed — LWW
• Individual PIs linked per drug below.

17. Awake Fiberoptic

Topicalization, sedation regimens:

• Cousins & Bridenbaugh, Neural Blockade in Clinical Anesthesia and Pain Medicine, 4e (2009) — Wolters Kluwer
• Apfelbaum JL, Hagberg CA, Connis RT, et al. 2022 ASA Practice Guidelines for Management of the Difficult Airway. Anesthesiology 2022;136:31-81 — DOI
• Glycopyrrolate antisialogogue — Robinul PI — DailyMed
• Lidocaine topical / nebulized — Xylocaine PI — DailyMed
• Dexmedetomidine sedation — Precedex PI — DailyMed

Topicalization technique and the sedation regimen: Ahmad I, El-Boghdadly K, Bhagrath R, et al. Difficult Airway Society guidelines for awake tracheal intubation in adults. Anaesthesia 2020;75(4):509-528 — PubMed. It prefers no single topicalization technique, gives lidocaine 1-10% with a maximum of 9 mg/kg lean body weight, and names remifentanil or dexmedetomidine as the single sedative agent, with midazolam only as an add-on.

Lidocaine total dose < 9 mg/kg topical:

• Williams KA, Barker GL, Harwood RJ, Woodall NM. Combined nebulization and spray-as-you-go topical local anesthesia of the airway. Br J Anaesth 2005;95:549-553 — PubMed

18. Difficult Airway Algorithm

Primary: ASA Practice Guidelines for Management of the Difficult Airway 2022.

• URL: https://doi.org/10.1097/ALN.0000000000004002
• Also the source of limiting the number of attempts at intubation or supraglottic airway placement, and tracking time, attempts and SpO₂.

Assessment thresholds and preoxygenation: Miller's 10e — Miller's. Box 28.1 for Mallampati III or IV, interincisor distance under 3 cm and thyromental distance under 6 cm as concerns (its Ch. 40 uses under 6.5 cm, 3 fingerbreadths); BMI of 30 kg/m² or more as a predictor of difficult (grade 3–4) mask ventilation and difficult intubation; and preoxygenation by 3 minutes of tidal volume breathing or 8 vital capacity breaths over 60 seconds.

A low Mallampati class does not exclude difficulty: Detsky ME, Jivraj N, Adhikari NK, et al. Will This Patient Be Difficult to Intubate?: The Rational Clinical Examination Systematic Review. JAMA 2019;321(5):493-503 — DOI. No clinical finding reliably excludes difficult intubation.

19. Procedural Sedation

Primary: Practice Guidelines for Moderate Procedural Sedation and Analgesia 2018: A Report by the American Society of Anesthesiologists Task Force. Anesthesiology 2018;128:437-479.

• URL: https://doi.org/10.1097/ALN.0000000000002043

ASA fasting standards (clear liquid 2 hr, etc.): see Section 12.

20. Blood Gas Interpretation

Acid-base / oxygenation formulas (Winters, anion gap, A-a gradient, Hb-binding) — references:

• Adrogué HJ, Madias NE. Management of life-threatening acid-base disorders. NEJM 1998;338:26-34, 107-111 — NEJM · PubMed
• Berend K, de Vries APJ, Gans ROB. Diagnostic use of base excess in acid-base disorders. NEJM 2018;378:1419-1428 — NEJM · PubMed
• Winters' formula (expected PaCO₂ = 1.5 × HCO₃⁻ + 8 ± 2): commonly attributed to Winters RW, The Body Fluids in Pediatrics, Boston: Little, Brown, 1973 (textbook; no online edition) — NLM catalog. Modern review: Albert MS, et al. Ann Intern Med 1967;66:312-322 (original metabolic-acidosis compensation data) — PubMed

21. Adult Drug Reference — Additions

Adult drug reference. Doses derived from FDA package inserts (DailyMed search URLs), standard anesthesia textbooks (Miller's 10e, Stoelting's 6e, Barash 9e), and the trial citations listed where evidence-based dosing applies. Pediatric versions of these drugs live in Section 8.

Sedation / Premedication

Antiarrhythmics & Code Drugs (ACLS doses per AHA 2020)

Volatile anesthetics (see also Section 7)

Cardiovascular — Vasodilators / Antihypertensives / Diuretic

Hemorrhage / Anticoagulation

Hormone / Metabolic

Antiemetics (full list)

Opioid additions + reversal

22. Surgical Antibiotic Prophylaxis

Three guidelines govern this content. The ASHP/IDSA guideline supplies agent selection and dosing; where it is silent by name on a procedure, the app cites the specialty guideline that names it.

Primary (agents + doses): Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery (ASHP/IDSA/SIS/SHEA). Am J Health Syst Pharm 2013;70:195-283.

• Free full-text PDF: https://www.idsociety.org/globalassets/idsa/practice-guidelines/clinical-practice-guidelines-for-antimicrobial-prophylaxis-in-surgery.pdf

Gynecologic procedures (named positions): ACOG Practice Bulletin No. 195, Prevention of Infection After Gynecologic Procedures. Obstet Gynecol 2018;131:e172-e189.

• URL: https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/06/prevention-of-infection-after-gynecologic-procedures

GI endoscopy (named positions): ASGE Standards of Practice Committee. Antibiotic prophylaxis for GI endoscopy. Gastrointest Endosc 2015;81:81-89.

• URL: https://www.asge.org/home/resources/publications/guidelines/antibiotic-prophylaxis-for-gi-endoscopy

Adult prophylaxis doses

All from the ASHP/IDSA guideline's dosing table:

Pediatric prophylaxis doses — surgical prophylaxis

All from the same guideline's pediatric dosing column: cefazolin 30 mg/kg (max 2 g), cefoxitin 40 mg/kg (max 2 g), clindamycin 10 mg/kg (max 900 mg), vancomycin 15 mg/kg, metronidazole 15 mg/kg (max 500 mg), gentamicin 2.5 mg/kg single dose. Clindamycin and gentamicin also cite Smith's Anesthesia for Infants and Children, 10th ed — Elsevier; clindamycin also cites the Cleocin Phosphate (clindamycin injection) PI (Pharmacia & Upjohn, label effective 2026-05-13) — DailyMed, for infusing slowly: hypotension and cardiopulmonary arrest have been reported after too-rapid intravenous administration.

Per-case positions (Cases library)

Each surgical case entry's Antibiotics field states the guideline position (indicated / not recommended / conditional) and names typical agents with allergy alternatives; it deliberately carries no doses — dosing lives on the drug screens above, so a dose exists in exactly one place. Positions cite the ASHP guideline where the ASHP/IDSA guideline names the procedure class, ACOG Practice Bulletin 195 for gynecologic procedures ASHP does not name (conization, hysteroscopic procedures, midurethral sling), and the ASGE 2015 guideline for endoscopy (ERCP drainage-dependent prophylaxis, EUS-FNA cystic-versus-solid split). Institutional protocols and current guidelines supersede in all cases.

2026-08-13 — the remaining 71 cases, and ten further guidelines

Until this date the Antibiotics field was present on 226 of 297 cases. The other 71 carried nothing at all, and there was no documented rule behind which ones — the field was simply optional and filled case by case. All 297 now carry it.

Three of the guidelines those entries needed were already cited above and were reused rather than duplicated: the ASHP and ASGE guidelines and ACOG Practice Bulletin 195. Ten further sources were added:

On the ACOG bulletin number. The source mapping behind this work flagged uncertainty over which ACOG bulletin is current, having surfaced the superseded Bulletins 74 (2006) and 104 (2009). This document already cited No. 195 (2018), which is the current one, and the new entries use it.

On AUA. The lithotripsy entry initially cited the AUA Best Practice Statement. It was re-sourced to the European guideline on 2026-08-13. AUA grants free access for an individual's clinical use only and requires a license in advance for any other purpose, naming a separate contact for commercial use. The copyright exposure was low — the entry states a fact in original wording, and facts are not copyrightable — but the terms are a contract claim rather than a copyright one, and a contract can restrict what copyright does not. Rather than resolve that for a single entry, it now cites a body whose guidance covers the same ground. No AUA-derived content remains in the app.

Four distinctions the entries state explicitly. Each is carried separately because collapsing it would change what a reader does:

• Therapy, not prophylaxis. Endoscopy for GI bleeding and peritonsillar abscess are marked therapy; trauma laparotomy is therapy if contaminated. Rendered like ordinary prophylaxis, these invite one preoperative dose and stop; for a cirrhotic variceal bleed that turns a seven-day course into a single dose.
• Insufficient evidence, stated as such — manual removal of placenta, postpartum D&C, and epistaxis control. "Insufficient evidence" is not "no": nobody having shown prophylaxis helps is a different claim from a body having recommended against it.
• Gated on cardiac risk — the two dental entries. The indication belongs to the patient, not the operation, and unqualified the row would read as "give antibiotics for dental work".
• The basis for the position, on every one of the 71 entries, and shown to the reader in words. The screen states one of three: guideline recommendation (17 entries); society statement, review, or category extrapolation (26); or no guideline addresses this — practice convention (28). So roughly two in five of these positions rest on no society guideline at all, and the app says which ones rather than leaving them all looking alike. The third phrasing is the one the screen colors, because it is the one that changes how far the entry can be leaned on.

One AHA 2021 change worth stating plainly: clindamycin is no longer recommended as an oral or parenteral alternative for penicillin-allergic patients requiring endocarditis prophylaxis, because it causes more frequent and severe reactions than the alternatives — use cephalexin or another first- or second-generation cephalosporin, azithromycin, or doxycycline. This does not apply to surgical prophylaxis, where clindamycin remains an accepted beta-lactam alternative per ASHP/IDSA, which is the only context in which this app uses it.

23. Surgical Cases Library — Specialty Guidelines

Case entries cite the anchor textbooks (Miller's 10e, Barash 9e, Stoelting's 6e, Coté 6e, Jaffe's Anesthesiologist's Manual of Surgical Procedures 6e, Smith's 10e, Cousins and Bridenbaugh's 4e, Hadzic's Peripheral Nerve Blocks 3e, Gray's Atlas of Ultrasound-Guided Regional Anesthesia 3e, NYSORA) and the guidelines elsewhere in this document. Where a case rests on specialty guidance not otherwise listed:

Gender-affirming surgery (hormone management): Coleman E, Radix AE, Bouman WP, et al. Standards of Care for the Health of Transgender and Gender Diverse People, Version 8 (WPATH SOC8). Int J Transgend Health 2022;23(Suppl 1):S1-S259.

• URL: https://www.tandfonline.com/doi/full/10.1080/26895269.2022.2100644

Medial branch radiofrequency ablation (awake stimulation testing): American Society of Pain and Neuroscience (ASPN) best-practice guideline on radiofrequency neurotomy. J Pain Res 2021. doi:10.2147/JPR.S325665

• URL: https://www.tandfonline.com/doi/full/10.2147/JPR.S325665

Bleeding risk with peripheral nerve and plane blocks: Tsui BCH, Kirkham K, Kwofie MK, et al. Practice advisory on the bleeding risks for peripheral nerve and interfascial plane blockade: evidence review and expert consensus. Can J Anaesth 2019;66(11):1356-1384.

• DOI: https://doi.org/10.1007/s12630-019-01466-w

Neurologic complications of regional anesthesia and pain medicine: Neal JM, Barrington MJ, Brull R, et al. The Second ASRA Practice Advisory on Neurologic Complications Associated With Regional Anesthesia and Pain Medicine: Executive Summary 2015. Reg Anesth Pain Med 2015;40(5):401-430.

• DOI: https://doi.org/10.1097/AAP.0000000000000286

Postpartum hemorrhage: American College of Obstetricians and Gynecologists. Practice Bulletin No. 183: Postpartum Hemorrhage. Obstet Gynecol 2017;130(4):e168-e186.

• DOI: https://doi.org/10.1097/AOG.0000000000002351

Urological infections, 2024 summary of the EAU guideline listed in Section 22: Kranz J, Bartoletti R, Bruyère F, et al. European Association of Urology Guidelines on Urological Infections: Summary of the 2024 Guidelines. Eur Urol 2024;86:27-41.

• DOI: https://doi.org/10.1016/j.eururo.2024.03.035

Benzocaine methemoglobinemia during transesophageal echocardiography: Novaro GM, Aronow HD, Militello MA, Garcia MJ, Sabik EM. Benzocaine-induced methemoglobinemia: experience from a high-volume transesophageal echocardiography laboratory. J Am Soc Echocardiogr 2003;16(2):170-175; and Sachdeva R, Pugeda JG, Casale LR, Meizlish JL, Zarich SW. Benzocaine-induced methemoglobinemia: a potentially fatal complication of transesophageal echocardiography. Tex Heart Inst J 2003;30(4):308-310.

• DOI (Novaro): https://doi.org/10.1067/mje.2003.5

Antibiotic prophylaxis for congenital diaphragmatic hernia repair: Flohr SJ, Mathew L, Hedrick HL, et al. Antibiotic exposure and infection epidemiology among newborns with congenital diaphragmatic hernia. J Perinatol 2025;45:1255-1261. A single-center cohort, not a guideline: no guideline names this operation.

• DOI: https://doi.org/10.1038/s41372-025-02389-9

Antibiotic prophylaxis positions in case entries: see Section 22 (ASHP/IDSA 2013, ACOG PB 195, ASGE 2015).

24. Pediatric Caudal Block — Dosing

The caudal block's Dosing tab uses its own weight-based pediatric tables, not the adult peripheral or adult neuraxial lists. Two anchor sources:

Ceilings and adjuvant set: Suresh S, Ecoffey C, Bosenberg A, et al. ESRA/ASRA Recommendations on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia. Reg Anesth Pain Med 2018;43:211-216.

• PubMed: https://pubmed.ncbi.nlm.nih.gov/29319604/

Under-6-months reduction, caudal morphine, epinephrine/test dose: Coté, Lerman, Anderson. A Practice of Anesthesia for Infants and Children, ch. 41 (Suresh, Polaner, Coté) — already Section 8's pediatric anchor.

Duration of action: ESRA/ASRA 2018, Table 2, Onset and Duration of Action and Potency of Various LAs, quoted verbatim below. This line previously credited Coté for onset and duration while the app's entries carried the ESRA/ASRA citation, and the two did not agree — corrected 2026-09-12.

Onset: removed from the app 2026-09-12, because no source states it as a figure. ESRA/ASRA Table 2 gives onset only as "Short" or "Intermediate", with no minutes. The minute ranges on the Dosing tab (bupivacaine 15–30 min, ropivacaine 10–20 min) are character-for-character identical to the adult peripheral table, which is the likeliest explanation for them. They are no longer shown: an unsourced figure a clinician reads as pediatric-specific, when it is adult peripheral data, is worse than no figure, and the row renders nothing when onset is absent.

Searched 2026-09-12, full text: Coté & Lerman 6e (5,493 pages), Smith's Anesthesia for Infants and Children 10e (1,670 pages) and Hadzic's Peripheral Nerve Blocks 3e. Seven pages in Coté name bupivacaine or ropivacaine alongside the word onset and all seven were read: agent choice depending on "desired speed of onset", bicarbonate speeding onset, lidocaine–bupivacaine mixtures for "rapid onset", onset of seizures in infant rats, onset of motor block as a catheter-migration warning, the index, and the back-cover dosing card — whose only onset column is for midazolam. No local anesthetic onset figure for a caudal, or for any block, appears in any of them. Extraction was verified sound before concluding: 0.2% near-empty pages, 1,849 characters per page, 192 pages naming the amides.

Encoded values (all weight-based; no adult absolute caps):

25. Post–Cardiac Arrest Temperature Control (TTM)

Primary: Perkins GD, Callaway CW, Kudenchuk PJ, et al. 2025 American Heart Association Guidelines for CPR and Emergency Cardiovascular Care — Part 11: Post–Cardiac Arrest Care. Circulation.

• AHA Journals: https://www.ahajournals.org/doi/10.1161/CIR.0000000000001375
• ECC portal: https://cpr.heart.org/en/resuscitation-science/cpr-and-ecc-guidelines/post-cardiac-arrest-care

Part 11 replaces the 2020 "32–34 or 36–37.5 °C, either acceptable" presentation with a single continuum: hypothermic (32–34 °C) and normothermic / fever-prevention (36–37.5 °C) temperature control, selecting and maintaining a constant target within that range, then actively preventing fever above 37.5 °C. The 2023 AHA focused update (TTM2, CAPITAL CHILL) is what revised the earlier recommendations.

Duration, quoted verbatim from the Part 11 recommendation table:

It is reasonable that temperature control be maintained for at least 36 hours in adult patients who remain unresponsive to verbal commands after return of spontaneous circulation (ROSC).

Scope limit. The 36-hour recommendation is stated for adult patients and is not used on the pediatric screen. Pediatric durations are separate and longer, and are given below.

25b. Pediatric post-arrest TTM — post-resuscitation care

Primary: Pediatric Post–Cardiac Arrest Care: A Scientific Statement From the American Heart Association. Circulation.

• AHA Journals: https://www.ahajournals.org/doi/10.1161/CIR.0000000000000697

The statement attributes the duration recommendation to the 2015 AHA PALS guidelines update and quotes it directly:

To treat the child who remains comatose after OHCA, the 2015 AHA PALS guidelines update recommended that it is reasonable either to maintain continuous normothermia (TTM to 36 °C–37.5 °C) for 5 days or to maintain 2 days of continuous hypothermia (TTM to 32 °C–34 °C) followed by 3 days of continuous normothermia (TTM to 36 °C–37.5 °C).

Underlying trials: THAPCA-OH and THAPCA-IH, in children >2 days and <18 years, comatose within 6 hours of ROSC. The hypothermia arm was cooled to 32–34 °C for 48 h, rewarmed over 16–24 h, then held at 36–37.5 °C until 120 h from initiation; the normothermia arm was held at 36–37.5 °C for 120 h. Neither trial found a significant difference in 1-year survival with favorable neurological outcome, and THAPCA-IH was stopped early for futility.

Note on sourcing: a secondary summary of this recommendation gave the rewarming rate as 0.25–0.5 °C/h. The primary statement says 0.5 °C every 2 hours (= 0.25 °C/h), which is the more conservative figure and the one encoded. This is why the number was not taken from the summary.

26. Society guidelines and reference compendia

The app names a source on screen for each value, and these are the society guidelines and reference works cited across it. The usage count on each says how much of the app rests on that source; the total is 59 referenced sources across the drug reference, the surgical case library, the block dosing data and every citation a screen renders.

PONV — Fifth Consensus Guidelines (7 uses) Gan TJ, Jin Z, Ayad S, et al. Fifth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting: Executive Summary. Anesth Analg 2026;143(3):497-513 (published online 14 November 2025).

• Distinct from §9 (Apfel 1999), which is the risk score. These are the guidelines that drive the app's prophylaxis and rescue choices.

Surviving Sepsis Campaign 2021 (2 uses) Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Intensive Care Med 2021.

• https://link.springer.com/article/10.1007/s00134-021-06506-y

NYSORA — New York School of Regional Anesthesia (24 blocks, one page each) NYSORA, Compendium of Regional Anesthesia. https://www.nysora.com/

• No longer cited as a compendium. Until 2026-09-10 all 24 of these blocks cited the string "NYSORA Compendium of Regional Anesthesia" with no chapter, page or URL, so a clinician who doubted a number had nowhere to go. That was the content audit's objection. Each block now cites the specific page it rests on, fetched and verified on 2026-09-06, and §30.1 lists them.
• A continuously revised web resource, not a fixed edition, so it carries no year. Cited for block anatomy, sonoanatomy and approach description — not for local anesthetic doses or maxima, which follow §1 and the block dosing engine. Where a block's technique rests on a specific paper, that paper is cited directly (see §8c for the obturator block).
• Six of those pages disagree with a figure the app publishes beside them — interscalene and axillary and femoral on volume, PECS and lateral femoral cutaneous on depth, popliteal sciatic on both. Interscalene was resolved on 2026-09-10; the other five are recorded in each citation and are open clinical questions, not citation errors.

ASA Standards for Basic Anesthetic Monitoring — 29 uses: 28 in the case library, 1 in the drug reference American Society of Anesthesiologists, Standards for Basic Anesthetic Monitoring. Last amended October 15, 2025.

• ASA standards index: https://www.asahq.org/standards-and-practice-parameters
• The most-cited source in the case library after the anchor textbooks. Nearly every case entry's monitoring statement rests on it — "standard monitoring applies in full regardless of venue" and its equivalents.
• The amendment date was read from the ASA page by hand: asahq.org blocks automated retrieval, so it cannot be checked mechanically. Re-check it when the standard is next amended.

ASA Physical Status Classification System — used by the ASA physical status tool American Society of Anesthesiologists, Statement on ASA Physical Status Classification System.

• ASA standards index: https://www.asahq.org/standards-and-practice-parameters
• Recorded as the 2020 version. Same caveat: not verified against the ASA page from here.
• Cited by one screen, the ASA physical status tool.

Generic by nature. Package-insert citations (26 uses) name a label rather than one document, and are covered by the FDA and DailyMed note in the preamble. The Broselow tape is cited by §28 (pediatric airway sizing).

27. Mixed local anesthetics — additive toxicity and fractional dosing

Primary (additivity): Neal JM, Barrington MJ, Fettiplace MR, et al. The Third American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Local Anesthetic Systemic Toxicity. Reg Anesth Pain Med 2018;43:113-123.

• https://pubmed.ncbi.nlm.nih.gov/29356773/
• Contains the recommendation that clinicians be aware of the additive nature of local anesthetic toxicity and adjust dosing accordingly. ASRA's own grading of that recommendation is Class II, Level B.
• The app's LAST citation points at this advisory, with the 2020 LAST Checklist noted as an addendum. That distinction matters: the checklist is treatment-only and does not carry the additivity recommendation, so a citation naming only the checklist would not support the dosing rule.

Supporting (fractional-dosing arithmetic and duration): Pro-Con: Mixing Local Anesthetics — Best of Both Worlds or Playing With Fire? ASRA Pain Medicine News, February 2026.

• https://asra.com/news-publications/asra-newsletter/newsletter-item/asra-news/2026/02/09/pro-con--mixing-local-anesthetics--best-of-both-worlds-or-playing-with-fire
• States that maximum doses for mixtures should be calculated as the sum of fractional contributions, and that mixtures commonly run shorter than the long-acting agent alone.
• Honest about the gap: no society has published a formal mixed-agent dosing standard. The fractional rule follows from the graded additivity recommendation above rather than from a published mixed-agent maximum.

What the app states. Maximum dose for a mixture is fractional — each agent as a percentage of its own maximum, summed to no more than 100% — with the additive nature of the toxicity stated explicitly. If toxicity is additive, a full lidocaine maximum plus a full bupivacaine maximum is by definition a 2× toxic dose.

Duration is given as 6–10 h, which sits below plain bupivacaine 0.5% at 8–16 h and is consistent with the shortening the pro-con article describes. A mixture should not be chosen for duration.

28. Pediatric airway sizing

Sources. Each row carries its own, in the Source column below. Until the citation review all ten shared two: the ETT formulas to Coté 6e and the LMA and blade bands to the Broselow Pediatric Emergency Tape (2025 edition, Luten R, ed.), which is still the tape those bands are read from.

Oropharyngeal and nasopharyngeal airways

Sources. ERC 2021 Paediatric Life Support (ERC 2021) for the landmark methods and the indications; StatPearls for the NPA age/ID table; and two MRI validation studies, GUEDEL-I (the Guedel airway study) and WEND:LI (the MRI validation study).

The app deliberately departs from the plain ERC landmark in two places, and the studies are cited to justify it:

• OPA sizing — the weight formula is computed and the incisors-to-mandible landmark is offered as the alternative, rather than the landmark alone.
• NPA depth — nostril to tragus minus 10 mm, rather than plain nostril to tragus.

OPA. GUEDEL-I imaged 94 anesthetized children sized by incisors-to-mandible: 47.9% correctly sized, 23.4% undersized (tongue protrusion in 59.1% of those), 28.7% oversized. Of five facial landmarks compared, incisors-to-mandible was the best but reached only 41.2% probability of correct sizing. A weight formula — 22.43 + 17.54 × log(weight kg) — outperformed every landmark at 61.7%. The app therefore computes the weight formula and gives the landmark as the alternative.

NPA. WEND:LI imaged 92 sedated children. Plain nostril-to-tragus, which is what ERC 2021 recommends, was optimal in only 13.0% and sat too distal in 71.7%. Nostril-to-tragus minus 10 mm reached 40.2%, the best of three methods tested. The app carries the minus-10-mm figure and says why.

Bounded above ~30 kg, deliberately. The formula was derived in young children (study mean age 4.7 y) and is untested above that range. Above it, size goes by build rather than by age — 70 mm, 80–90 mm, and genuinely up to 100 mm (Guedel 5) in a tall male. The formula keys only on weight and cannot see build: at 70 kg it returns 97 mm, a Guedel 5, whatever the patient's build. If that is too large, it errs in the dangerous direction — an oversized OPA can displace the epiglottis over the laryngeal inlet and obstruct completely, a worse outcome than the problem being treated. Above roughly 30 kg the app therefore stops computing and returns the landmark, which can at least see the patient.

A note on the age labels, because this looks like an error and is not. The formula returns ~72 mm for a 4-year-old, which can look too large for the age. That is expected: the sizes compress at the top end. The packaging labels do not help: suppliers put different ages on the same size.

Natural log, and the alternative is now excluded. log₁₀ was tested against the full weight range and fails outright — it returns 32 mm for a neonate and 55 mm for a 70 kg adult, moving barely 23 mm across a twenty-fold weight range. The source writes "log" without a base. Checked against GUEDEL-I's own population (mean age 4.7 y, ≈18 kg): ln gives 73 mm, a Guedel 2, which is right for that child; log₁₀ gives 44 mm, a Guedel 00 — a neonatal airway for a four-year-old, which cannot be what the study found. The natural log is the base used here; verify against the paper before treating the computed value as authoritative.

Standing of these numbers. Same caveat as the tube formulas: neither landmark reliably predicts size, and across roughly 190 children the best available method for either device was correct in about 40–48% of cases. Neither study found clinical harm from the imprecision. These are first estimates requiring confirmation after insertion — chest rise, breath sounds, capnography, absence of tongue protrusion, and for the NPA a look in the mouth to confirm the tip is not visible below the uvula.

Guedel length tolerances. Only sizes 00 (40 mm ± 2.5) and 1 (60 mm ± 2.5) were confirmed against a formal specification with stated tolerances (EN ISO 5364:2016, via UNFPA). The other nominal lengths are the widely published values and are consistent across the manufacturer catalogs reviewed. Age labels printed on packaging are not consistent between manufacturers — UNICEF labels the 60 mm airway "child" where a commercial kit labels 60 mm "infant". Size by measurement, never by the box.

Depth at the lip — the qualifier

From 1 year the depth is the age formula at the lip: 12 + age/2 from 2 years, and 11 cm from 1 to 2 years. Smith's 10th edition prints the age formula as an oral depth measured from the lips, on the same page as 3 × the tube's internal diameter. The app used 3 × ID until September 2026 and changed because the two were compared directly: in children under 7, 3 × ID put 10.7% of tubes into a bronchus against 2.1% for the age formula, whose misses were mostly shallow (Shim 2023).

The number tracks the child, not the tube. A half-size smaller cuffed tube does not change it, and a larger tube does not deepen it.

The landmark is part of the number. Studies of these formulas have measured from the front teeth (Ebenebe 2023) and from the gum, and in neonates the lip reads about 0.5 cm more than the gum (Zaytseva A, et al. J Matern Fetal Neonatal Med 2020 — DOI). A depth quoted without its landmark can be half a centimeter off before the tube moves.

Every formula is approximate. In children 4 to 12 the age formula ran about 1 cm shallow, and height-based formulas were more accurate: 4 + 0.1 × height (cm) placed 85% of tubes optimally against 61% for the age formula (Zhuang PE, et al. J Clin Anesth 2023 — DOI; Zhang Y, et al. Pediatr Res 2025 — DOI). Confirm every tube by auscultation and capnography, and by chest x-ray or ultrasound where available.

The 6 + weight rule is NEONATAL, not "under 1 year". 6 + weight is the 7-8-9 rule, which for neonates estimates depth to the lip from weight: 1 kg = 7 cm, 2 kg = 8 cm, 3 kg = 9 cm. It does not extend past the newborn period.

Standing of the rule. The age formula and 6 + weight are widely reproduced clinical rules from the pediatric anesthesia texts — not society recommendations — and are cited to the texts and the studies that tested them. Both are estimates requiring confirmation, not targets.

29. Perioperative care of transgender and gender diverse adults

Primary: Harding D, Marsh S, Lennie Y. Perioperative considerations for transgender and gender diverse adults. BJA Education 2023;23(4):136-143.

• https://www.bjaed.org/article/S2058-5349(23)00005-7/fulltext
• Open archive. bjaed.org returns 403 to automated retrieval — bot-blocking, not a paywall; the article loads in a browser. Read in full 2026-08-11.

The anesthesia-specific anchor for the two gender-affirming entries. WPATH SOC8 remains the standard-of-care document; this review carries the intraoperative specifics SOC8 does not, and it replaced borrowed general-medicine citations on both entries.

Five items it contributed that nothing else in this project had:

What it settled about two open questions:

• Estrogen and VTE — the "variable" position is retained, and sharpened. The article supplies the mechanism (estrogen raises fibrinogen, factor VII and factor X while reducing antithrombin III and protein S) and the cost of stopping: "depression, irritability, autonomic hyperactivity and a reduced seizure threshold." The last is an anesthetic concern in its own right and was absent from the entry. It also records that WPATH "found no evidence of an increased risk of VTE in patients continuing their hormone therapy before surgery compared with those stopping it." So the evidence is converging while practice still varies — the entry now says exactly that instead of an undifferentiated "variable."
• Testosterone — confirmed a hematocrit question, not a VTE one. Verbatim: "TGDIs on oestrogen therapy have reduced hemoglobin, haematocrit and creatinine whereas those taking testosterone may have increased levels."

30. Regional blocks — sources, depth, coverage

The app ships 28 regional blocks. This section gives the source, depth and volume carried by each one, with the full citations at the end. Related material sits elsewhere: the obturator block in §8c, block adjuvants in §5, the pediatric caudal in §24, and mixed–local anesthetic toxicity in §27.

Every value below is transcribed from the block data the app ships, so this document cannot claim a citation the app does not carry.

30.1 Source, depth and volume, per block

Every block carries at least one source; 28 of 28 carry two or more.

30.2 Coverage and misses

The Overview card states what a block covers and what it misses, rather than onset and duration — which the local anesthetic decides, not the block. "Not covered" and "Unreliable" are kept apart deliberately: a territory the block never reaches is a different clinical fact from one it reaches inconsistently.

9 of 28 blocks carry an Unreliable entry; for the rest the distinction does not arise.

30.3 Probe orientation and starting position

All 27 of 28 blocks carry probe orientation and a starting landmark. These are technique descriptions drawn from the block's cited sources, not separate claims — the citation for each row is the block's own source list in §30.1.

30.4 Full citations

Every source cited by the 28 regional blocks above, in full.

No direct URL for Hadzic 2022 — textbooks and subscription compendia. See "Sources without a confirmed direct URL".

31. Airway and access device tables

Sourced 2026-08-24. Every citation below was verified against the source before use. Where a value cannot be traced to a retrievable source, the row says so — there is no middle grade, and a number resting on convention is marked as such rather than dressed up as a citation.

Central venous catheter depth

Reference frame: skin puncture site to catheter tip. It is a field on every row. Skin-to-hub and skin-to-tip differ by several centimeters, in the right-atrium direction.

Population limit worth stating: Kim's cohort was Korean, and the paper frames its recommendations as more accurate than Peres for that population. Height differences move insertion depth, so these figures are not automatically transferable.

Why fixed depths rather than Peres. Peres PW. Anaesth Intensive Care 1990;18(4):536-9 (PMID 2268022) gives height-based formulae, and his own series put 24% of catheters in the right atrium. Later work reports 48% over-insertion using Peres blindly. Kim's fixed depths outperformed Peres 91.5% to 77.4% in the study that produced them. The fixed values are the safer default, and that is why the table carries them.

LMA sizing — the device is part of the number

Device: LMA Classic. The size numbers are shared across the LMA family and the maxima are not: a size 4 is 30 mL on the Classic and 45 mL on the Supreme, so an unlabeled "size 4 to 30 mL" is right for one device and out by 15 mL for another. Naming the device is the citation.

Status of the seven volumes and weight bands: not verified against the manufacturer's instructions for use, which could not be retrieved. Three independent secondary sources concur on all seven. Concurrence across three sources is real corroboration and it is still not the primary document, so the distinction is stated rather than collapsed. A Teleflex product-literature PDF confirms the ≤60 cmH₂O rule and lists the 2015 Classic instructions in its own reference list; the Supreme figures were retrieved from Teleflex's data sheet directly.

The pressure line is verified. Ruananukun N, et al. BMC Anesthesiol 2020, doi:10.1186/s12871-020-01028-4 (PMID 32380954) measured intracuff pressure at the maximum recommended volume across four adult LMA models and found it exceeded 60 cmH₂O in every type and size tested; roughly half the maximum volume reaches 60 cmH₂O, two-thirds for the ProSeal.

The screen carries that as its own card, because a maximum is not a target. A volume column with no pressure line invites inflating to a ceiling that reliably overpressurizes.

Nasopharyngeal airway sizing — diameter and length are separate columns

The pediatric rows are millimeters of internal diameter. The adult rows are centimeters of length. They are held as two fields rather than one, because the numerals collide exactly: 6–7, 7–8 and 8–9 are both the adult length convention and the familiar adult diameter convention in millimeters. A reader arriving from seven consecutive millimeter rows can read a length as a diameter and be wrong by a whole dimension.

One gap recorded rather than smoothed: that pediatric table gives its numbers without units. They are carried here as millimeters of internal diameter, which is the convention and is consistent with the range, but the source does not say so.

Sizing method — Roberts K, Porter K. How do you size a nasopharyngeal airway. Resuscitation 2003;56(1):19-23. Ten subjects, coronal MRI; neither the little-finger nor the anterior-nares method correlated with the subject's own nasal anatomy. The paper concludes that sizing should follow patient size, sex and race. A further claim attributed to it — that length matters more than diameter, after Stoneham 1993 — could not be confirmed and is not carried.

Oropharyngeal airway sizing — a definition and a convention in one row

The length figure is overall length, flange to distal tip.

• The ISO column is definitional. ISO 5364 (current edition 2016) designates oropharyngeal airway size by length. Confirmed from the standard's scope; the standard document itself has not been read here.
• The Guedel column is convention. Guedel numbering is manufacturer-specific and vendors disagree — at least one catalogs Guedel 000 as ISO 3.5 and Guedel 5 as ISO 12, against the 3 and 10–11 carried here.

So the ISO-to-length mapping is a definition and the Guedel-to-ISO mapping is a supplier-dependent convention, sitting side by side in the same row. The screen says to size by measurement rather than by the number on the box, which is the practical consequence.

Postpartum hemorrhage — two live definitions, not one stale one

500 mL and 1000 mL are not out of date. They are unattributed, and the attribution changes the number:

• ACOG (reVITALize 2014; Practice Bulletin 183, October 2017): cumulative blood loss ≥1000 mL, or blood loss with signs or symptoms of hypovolemia, within 24 hours, regardless of route.
• WHO and FIGO: >500 mL vaginal, >1000 mL cesarean.

ACOG also retains that >500 mL after vaginal delivery is abnormal and warrants investigation, so a 500 / 1000 entry may be recording that caveat rather than the WHO definition — different claims wearing the same numerals.

Both definitions are current. There is no newer one to move to, only an attribution to state.

The glossary is deliberately unsourced

1 of its 102 entries carries a verified citation — the postpartum hemorrhage entry above. The remaining eleven numeric entries are unverified, and at least five of those (CICO, EBV, IBW, MH, VBG) carry a number whose meaning depends on a denominator, a base case, or a comparator that the entry may not state.

Sourcing the glossary is outstanding work, recorded here rather than implied by omission.

32. Double-lumen tube sizing

Sourced 2026-08-24. Every citation below was verified against the source before use.

The table

Left double-lumen tube size by sex and height, following Slinger's protocol as reproduced in the review cited below.

Not verified against Slinger's own paper, which could not be retrieved. It reaches this document through the review below, which reproduces the protocol. That is the strongest statement the sourcing supports.

The method caveat is the important part

This is not one school of thought against another.

Slinger's own position is that no topic in thoracic anesthesia has less consensus than how to size a left double-lumen tube, and the review reproducing this protocol states outright that no literature guidelines exist for the choice. Sizing by sex and height is convention with no guideline behind it, and the alternative — measuring tracheal width on imaging — is not a settled replacement either.

The review also disagrees with the protocol it reproduces: Eldawlatly recommends smaller tubes than Slinger's height bands give — 35 Fr for women and 37 Fr for men — on airway-trauma grounds. Two positions in one paper, and the table follows the protocol rather than the editorial.

Brodsky's imaging brackets, for the alternative method: tracheal width measured at the level of the clavicles on a PA chest radiograph — ≥18 mm → 41 Fr, ≥16 mm → 39 Fr, ≥15 mm → 37 Fr, ≥14 mm → 35 Fr.

Sources, and how far each was verified

Two claims worth chasing, not asserted in the app

Both were supplied without a retrievable identifier, so neither is stated anywhere the user can see. They are recorded here because they matter if they hold:

• "When in doubt, go smaller" may not be the safe default. A systematic review of double-lumen-tube tracheobronchial injury is reported to have found most injuries occurred with 35 Fr and 37 Fr tubes. If that holds, the conservative-sounding choice carries its own mechanism, and Eldawlatly's smaller-tube recommendation sits against it.
• French size does not determine dimension across manufacturers. A study of 171 tubes from four manufacturers is reported to have found the bronchial cuff segment diameter did not decrease consistently with nominal size, with major overlap between sizes. This is the same device-identity problem as the LMA table one section above: the number on the package is not the dimension.

33. Complication Rates

The complication rates shown on each block card, with the source for each. A figure is either traced to a source that states it, or it is marked as not traced — there is no middle grade.

A complication percentage is only meaningful with its definition. Several of these rates move by a factor of two to six depending on how the complication was defined, by what imaging method, and at what timepoint — more than they move with the drug or the volume. Where that is true it is said in the row.

Every complication figure is traced to a source that states it.

Where a single number is the wrong shape. Three of these complications vary by more than an order of magnitude with something other than the block — guidance method for infraclavicular vascular puncture, laterality for paravertebral pleural injury, and the choice of definition for costoclavicular diaphragmatic paresis. Those rows give the stratification rather than an average of it, because an average across a sixteen-fold spread describes nobody.

A note on single-event rates. Several figures here rest on one or two observed events. A percentage computed from a single event has a confidence interval several times wider than the estimate itself, so it presents as a measurement when it is an observation. Where that is the case the raw fraction is given instead — "1 case in 520" rather than "0.2%".

Two open questions on the paravertebral figures. A published overview attributes a different set to Lönnqvist 1995 — 319 adults, pneumothorax 0.3%, pleural puncture 0.9% — which may be the adults-only subgroup of the same cohort. If it is, an adult-focused reference arguably wants 0.3%. Settling it needs the primary paper. Separately, both source studies predate routine ultrasound; the modern comparator is Pace MM, Sharma B, Anderson-Dam J, et al. Anesth Analg 2016;122:1186-1191, and its rates are not yet incorporated.

34. Equipment sizing tables

Sourced 2026-08-22.

The landmark is part of the number

Every depth in this table is measured tip-to-lip, and the landmark travels with the value — on screen and in the underlying data.

That matters because the reference point is not universal. NRP's 9th edition (AAP, November 2025) moved to the anterior edge of the upper gum at the midline, for a more consistent anatomical reference and less over-insertion. The gum sits behind the lip, so the same tube tip reads roughly 0.5–1 cm shallower at the gum. A depth without a stated landmark is not a usable number, and a mixed column without labels invites comparing two figures that are not comparable.

The neonatal values here are transcribed from NRP 8th edition, which states them at the lip. The 9th edition's numeric table has not been read here, so this table stays on the one edition it can cite, at the landmark that edition uses.

Row by row

The neonatal rows are transcribed from a primary source in hand. The pediatric rows are the formulas the literature specifies, applied inside their stated age ranges. The depth conventions and the adult rows are convention, not citation — widely taught, with no single source that states them, and marked that way rather than given a reference they do not have.

NRP 8th edition, Lesson 5 — the two source tables

Table 5-1, verbatim (NRP 8th ed., Lesson 5, p. 126):

Table 5-4, titled "Tip to Lip" (NRP 8th ed., Lesson 5, p. 137), adapted from Kempley ST, Moreiras JW, Petrone FL. Endotracheal tube length for neonatal intubation. Resuscitation 2008;77(3):369–373:

Two indexes, and they do not line up. Depth is banded by gestational age; tube size is banded by weight. The 27–29 wk depth band straddles the < 28 / 28–34 size boundary. The size rows therefore carry depth as a range, which spans a boundary without collapsing it:

The first two ranges share 6.5 cm because a 27-week and a 28-week infant genuinely take the same depth. That overlap reports the source faithfully.

When the gestation is known and a range is not good enough, the app carries Table 5-4 row by row as its own gestational-age-indexed table.

Below 1 year, a gestational age is required

Below 1 year the age-based size formulas are suppressed, and depth is never computed from tube size. With a stated gestational age, Coté's weight bands size the tube and Table 5-4 gives depth. Without one, the airway fields read "—".

Age 0 spans twelve months, which is why both directions have to be blocked. The age formula returns a 4.0 for a newborn who takes 2.5 to 3.5 by weight. A newborn resuscitation table applied to a nine-month-old is the same out-of-range error pointing the other way — a 9 kg infant is not a "greater than 2 kg newborn." Stating a gestation is what declares the patient a newborn, and without one the correct output is no output.

Above 1 year, depth is 3 × the internal diameter of the age-based size. Downsizing for a cuff does not shorten the depth: 3 × a smaller tube can sit above the cords, so the depth holds at 3 × the size the patient takes on size grounds. If the downsize is for airway pathology rather than for a cuff, an age-based depth formula should be used instead.

The half-size gap between cuffed and uncuffed

Uncuffed sizes round down; cuffed sizes round to nearest. An oversized uncuffed tube is the hazard — there is no cuff to absorb the mismatch and the pressure lands on the subglottic mucosa — so rounding down is the conservative direction.

Rounding the two directions differently makes them collide: at ages 3, 5, 7 and 9 the formulas return the same value for both. The cuffed size is therefore clamped to exactly uncuffed − 0.5, which is the relationship stated in the rule printed beside the number. The clamp dominates the formula at every age, which is worth saying plainly rather than implying both do work; the formulas are kept because they are what the literature specifies.

Two empty cells, and why they are empty

No cuffed tube for newborns. NRP 8th ed Lesson 5 lists 2.5, 3.0 and 3.5 as the routine sizes and says 2.0 mm, 4.0 mm and "tubes with inflatable cuffs are available and may be considered for specific indications but are not routinely used during neonatal resuscitation."

Beyond NRP: the smallest cuffed tube manufactured is 3.0 mm ID, and the prevailing recommendation is uncuffed below 3 kg. A newborn under 34 weeks takes a 2.5 or 3.0 uncuffed tube by Table 5-1, so across the entire preterm range there is no cuffed tube made in the size that patient needs. The empty cell is the answer, not a gap in it. Not verified against a society table — the 3.0 mm floor and the 3 kg threshold are review-level consensus.

No 2.0 tube. The chapter carries 2.5, 3.0 and 3.5 as the routine sizes and mentions the 2.0 with no weight band at all. A widely used provincial cognitive aid bands it to ≤ 1200 g, which would offer a 2.0 to an 1100 g infant on the authority of a table that does not say that. The 2.0 is withheld.

Citations

Every depth here is an estimate requiring confirmation

Auscultation and ETCO₂, not this table — including the rows that come from a formula or from a society table.

Still open

• Page numbers within Smith's 5th ed are cited as 269–275; some sources give 272–275.
• The NRP 9th edition's numeric depth table has not been read here. Until it is, this table stays on the 8th, at the lip.

35. PubMed URLs for cited journal articles

Quick links to all journal articles cited above. URLs go to the PubMed abstract page; full text usually requires institutional login.

Notes on page numbers

Textbook page numbers vary by edition. Where this document cites a chapter (e.g., "Miller's 10e Ch. 47 'Local Anesthetics'"), the chapter title is the stable reference — find the chapter in your edition rather than relying on a page number. ClinicalKey institutional access provides full text + chapter navigation for Miller's, Coté, and Stoelting's.

36. Sources without a confirmed direct URL

A small number of cited sources do not have a verifiable direct URL (either pre-internet publications, journals discontinued before PubMed indexing, or society documents distributed only as PDFs to members). For these, I cite the original reference and provide the closest verifiable lookup (society root page or PubMed search):

If you have a verifiable direct URL for any of the citations above, please email support@helixanesthesia.com so we can add it.

37. Answer pages — cited sources

Every source cited on a published answer page, grouped by page and numbered as it appears there, so a reference in the text can be found here without opening the page.

740 references across 33 pages, taken from the pages themselves.

Anesthetic considerations for Ehlers-Danlos syndrome

Published at /answers/anesthetic-considerations-ehlers-danlos-syndrome.

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2. Wakabayashi R, Tanaka S, Tsuchiyama K, et al. Anesthetic management of a patient with musculocontractural Ehlers-Danlos syndrome undergoing scoliosis surgery. JA Clin Rep. 2020;6:41. doi:10.1186/s40981-020-00352-5
3. Wiesmann T, Castori M, Malfait F, Wulf H. Recommendations for anesthesia and perioperative management in patients with Ehlers-Danlos syndrome(s). Orphanet J Rare Dis. 2014;9:109. doi:10.1186/s13023-014-0109-5
4. Lam AL, Mittal N, Vinod M, et al. The association of point-of-care coagulation testing with bleeding symptoms in patients with Ehlers-Danlos syndrome: an exploratory cross-sectional study. Can J Anesth. 2025. doi:10.1007/s12630-025-03048-5. PMID 41419706. Toronto General Hospital GoodHope EDS Clinic cohort; ROTEM, PlateletWorks and ISTH-BAT.
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6. Chopra P, Bluestein L. Perioperative care in patients with Ehlers Danlos syndromes. Open Journal of Anesthesiology. 2020;10(1):13–29. doi:10.4236/ojanes.2020.101002. Review of coexisting conditions including dysautonomia, MCAS, Chiari malformation, craniocervical instability, gastroparesis, and altered local anesthetic response.
7. Lane D. Anaesthetic implications of vascular type Ehlers-Danlos syndrome. Anaesth Intensive Care. 2006;34(4). doi:10.1177/0310057X0603400412. PMID 16913351
8. Daneshvar H, Abtahi D. Perioperative anesthesia management in a patient with Ehlers-Danlos syndrome: a case report of scleral buckling surgery. Arch Anesth Crit Care. 2026. doi:10.18502/aacc.v12i3.21319.
9. Arendt-Nielsen L, Kaalund S, Bjerring P, Høgsaa B. Insufficient effect of local analgesics in Ehlers Danlos type III patients (connective tissue disorder). Acta Anaesthesiol Scand. 1990;34(5):358–361. doi:10.1111/j.1399-6576.1990.tb03103.x. PMID 2389651.
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11. Schubart JR, Schaefer E, Janicki P, et al. Resistance to local anesthesia in people with the Ehlers-Danlos syndromes presenting for dental surgery. J Dent Anesth Pain Med. 2019;19(5):261–270. PMID 31723666
12. Jacobs A, et al. Resistance to local anaesthetics administered via epidural, intrathecal and pudendal injections. Anaesth Rep. 2022;10(2):e12205. doi:10.1002/anr3.12205
13. Bourne KM, Thai S, Lei LY, et al. Patients with Ehlers-Danlos syndrome experience reduced effectiveness of lidocaine local anesthetic: a randomized cross-over clinical trial. Reg Anesth Pain Med. 2026. doi:10.1136/rapm-2025-107416. PMID 41775498. Note: this paper reports 44% versus 91% at 30 minutes in its abstract and 53% versus 80% in its results text, both at p = 0.003. The results-text figures are the ones quoted above.
14. Cesare AE, Rafer LC, Myler CS, Brennan KB. Anesthetic management for Ehlers-Danlos syndrome, hypermobility type complicated by local anesthetic allergy: a case report. Am J Case Rep. 2019;20:39–42. doi:10.12659/AJCR.912799
15. Aljuba YM, Shatalin D, Ronenson A, Grenader A, Ioscovich A. Anesthetic management of a pregnant patient with Ehlers-Danlos syndrome undergoing elective cesarean delivery: a case report. Cureus. 2025;17(8):e89400. doi:10.7759/cureus.89400
16. Ohashi N, Furutani K, Ishii H, Baba H. Perioperative brachial plexus injury caused by hyperabduction of the upper extremity in a patient with Ehlers-Danlos syndrome in the prone position. Masui. 2012;61(6):626–628. PMID 22746029.
17. Mast KJ, Nunes ME, Ruymann FB, Kerlin BA. Desmopressin responsiveness in children with Ehlers-Danlos syndrome associated bleeding symptoms. Br J Haematol. 2009;144(2):230–233. doi:10.1111/j.1365-2141.2008.07446.x. PMID 19036109.
18. Byers PH, Belmont J, Black J, et al. Diagnosis, natural history, and management in vascular Ehlers-Danlos syndrome. Am J Med Genet C Semin Med Genet. 2017;175(1):40–47. doi:10.1002/ajmg.c.31553
19. Jaiswal M, Mansoorshahi S, Zachariah S, et al. Varied presentations of arterial events in vascular Ehlers-Danlos syndrome. JACC Case Rep. 2025;30(32). doi:10.1016/j.jaccas.2025.105424. PMID 40938243
20. Ong KT, Perdu J, De Backer J, et al. Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial (BBEST). Lancet. 2010;376(9751):1476–1484. doi:10.1016/S0140-6736(10)60960-9. PMID 20825986.
21. Baderkhan H, Wanhainen A, Stenborg A, et al. Celiprolol treatment in patients with vascular Ehlers-Danlos syndrome. Eur J Vasc Endovasc Surg. 2021;61(2):326–331. doi:10.1016/j.ejvs.2020.10.020. PMID 33223285.
22. Lian T, Bhandari A, Shalhub S. What every vascular surgeon should know about vascular Ehlers-Danlos syndrome. Ann Vasc Surg. 2026;129:302–306. doi:10.1016/j.avsg.2026.03.032. PMID 41905459.
23. Khoury MK, Eagleton MJ. Iliac artery aneurysm endoleak management in a patient with vascular Ehlers-Danlos syndrome. J Vasc Surg Cases Innov Tech. 2024. doi:10.1016/j.jvscit.2023.101401
24. Chu LC, Johnson PT, Dietz HC, et al. Vascular complications of Ehlers-Danlos syndrome: CT findings. AJR Am J Roentgenol. 2012;198(2):482–487. doi:10.2214/AJR.11.6603. PMID 22268198
25. Bowen JM, Hernandez M, Johnson DS, et al. Diagnosis and management of vascular Ehlers-Danlos syndrome: experience of the UK national diagnostic service, Sheffield. Eur J Hum Genet. 2023;31:749–760. doi:10.1038/s41431-023-01343-7
26. Associated conditions. Malignant Hyperthermia Association of the United States. mhaus.org/healthcare-professionals/miscellaneous/associated-conditions. Accessed September 2026. Lists the conditions associated with malignant hyperthermia susceptibility — central core disease, King-Denborough syndrome, multiminicore disease, the muscular dystrophies, the myotonias, the periodic paralyses, osteogenesis imperfecta and carnitine palmityl transferase deficiency. Ehlers-Danlos syndrome is not among them.
27. Jeunemaitre X, Mousseaux E, Frank M, et al. Efficacy of irbesartan in celiprolol-treated patients with vascular Ehlers-Danlos syndrome. Circulation. 2025;151(10):686–695. doi:10.1161/CIRCULATIONAHA.124.072849. PMID 39906986.
28. Isselbacher EM, Preventza O, Hamilton Black J III, et al. 2022 ACC/AHA guideline for the diagnosis and management of aortic disease. J Am Coll Cardiol. 2022;80(24):e223–e393. doi:10.1016/j.jacc.2022.08.004
29. Green C, Ghali N, Akilapa R, et al. Classical-like Ehlers-Danlos syndrome: a clinical description of 20 newly identified individuals with evidence of tissue fragility. Genet Med. 2020;22(10):1576–1582. doi:10.1038/s41436-020-0850-1
30. van Gurp JE, Lechner RL, Micha D, et al. Tenascin-X deficiency causing classical-like Ehlers-Danlos syndrome type 1 in humans is a significant risk factor of gastrointestinal and tracheal ruptures. Clin Transl Gastroenterol. 2025;16(3):e00821. doi:10.14309/ctg.0000000000000821. PMID 39807789.
31. Blackburn PR, Xu Z, Tumelty KE, et al. Bi-allelic alterations in AEBP1 lead to defective collagen assembly and connective tissue structure resulting in a variant of Ehlers-Danlos syndrome. Am J Hum Genet. 2018;102(4):696–705. doi:10.1016/j.ajhg.2018.02.018. PMID 29606302.
32. Kumskova M, Flora GD, Staber J, Lentz SR, Chauhan AK. Characterization of bleeding symptoms in Ehlers-Danlos syndrome. J Thromb Haemost. 2023;21(7):1824–1830. doi:10.1016/j.jtha.2023.04.004. PMID 37179130.
33. Artoni A, Bassotti A, Abbattista M, et al. Hemostatic abnormalities in patients with Ehlers-Danlos syndrome. J Thromb Haemost. 2018;16:2425–2431. doi:10.1111/jth.14310
34. D’hondt S, Van Damme T, Malfait F. Vascular phenotypes in nonvascular subtypes of the Ehlers-Danlos syndrome: a systematic review. Genet Med. 2018;20:562–573. doi:10.1038/gim.2017.138. PMID 28981071.
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37. Ramírez-Paesano C, Rodiera Clarens C, Sharp Segovia A, et al. Perioperative opioid-minimization approach as a useful protocol in the management of patients with Ehlers-Danlos syndrome-hypermobility type, craniocervical instability and severe chronic pain who are to undergo occipito-cervical fixation. Orphanet J Rare Dis. 2023;18:214. doi:10.1186/s13023-023-02829-9
38. Schievink WI, Gordon OK, Tourje J. Connective tissue disorders with spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension: a prospective study. Neurosurgery. 2004;54(1):65–70. doi:10.1227/01.neu.0000097200.18478.7b. PMID 14683542.
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42. Corrao S, Ruggeri MI, Benedetto AD, et al. Vascular Ehlers-Danlos syndrome: a multidisciplinary clinical framework for early suspicion, emergency-safe management and lifelong care. J Intern Med. 2026. doi:10.1111/joim.70165. PMID 42798186.

Anesthetic considerations for Myasthenia Gravis

Published at /answers/anesthetic-considerations-myasthenia-gravis.

1. Daum P, Smelt J, Ibrahim IR. Perioperative management of myasthenia gravis. BJA Educ. 2021;21(11):414–419. doi:10.1016/j.bjae.2021.07.001. PMC8520038
2. Chigurupati K, Gadhinglajkar S, Sreedhar R, Nair M, Unnikrishnan M, Pillai M. Criteria for postoperative mechanical ventilation after thymectomy in patients with myasthenia gravis: a retrospective analysis. J Cardiothorac Vasc Anesth. 2018;32(1):325–330. doi:10.1053/j.jvca.2017.06.045. PMID 29221974
3. Neuman A, Hendrix JM. Anesthesia for patients with myasthenia gravis. In: StatPearls [Internet]. StatPearls Publishing; updated 28 March 2025. Bookshelf ID NBK572091
4. Binks SNM, Morse IM, Ashraghi M, Vincent A, Waters P, Leite MI. Myasthenia gravis in 2025: five new things and four hopes for the future. J Neurol. 2025. doi:10.1007/s00415-025-12922-7
5. Huang Y, Tan Y, Shi J, Li K, Yan J, Guan Y. Patients with myasthenia gravis with acute onset of dyspnea: predictors of progression to myasthenic crisis and prognosis. Front Neurol. 2021;12:767961. doi:10.3389/fneur.2021.767961
6. van den Bersselaar LR, Gubbels M, Riazi S, et al. Mapping the current evidence on the anesthetic management of adult patients with neuromuscular disorders—a scoping review. Can J Anaesth. 2022;69(6):756–773. doi:10.1007/s12630-022-02230-3. PMID 35322378. PMC9132812.
7. Claytor B, Cho SM, Li Y. Myasthenic crisis. Muscle Nerve. 2023;68(1):8–19. doi:10.1002/mus.27832. PMID 37114503
8. Carron M, De Cassai A, Linassi F. Sugammadex in the management of myasthenic patients undergoing surgery: beyond expectations. Ann Transl Med. 2019;7(Suppl 8):S307. PMID 32016026. Summarizing Gritti et al. and Fujita et al.
9. Kurnutala LN, Robison J. Top ten facts you need to know about anesthetic management of myasthenia gravis patients. J Miss State Med Assoc. 2024;65(11/12). doi:10.67225/001c.129850.
10. Li Y, Luo F, Chin JWE. Perspective chapter: anesthesia management strategy for patients with myasthenia gravis. In: Carmignano SM, Ancona E, eds. Myasthenia Gravis – Clinical Aspects and Therapies [working title]. IntechOpen; published online first 27 March 2026. doi:10.5772/intechopen.1014850. Also the source of the muscarinic signs of cholinergic crisis — hypersalivation, increased bronchial secretions, bradycardia and miosis — and of its management: stop the cholinesterase inhibitor, give atropine 0.5 to 1 mg intravenously for the muscarinic effects, and support ventilation where respiratory failure has developed.
11. Fernandes HDS, Ximenes JLS, Nunes DI, Ashmawi HA, Vieira JE. Failure of reversion of neuromuscular block with sugammadex in patient with myasthenia gravis: case report and brief review of literature. BMC Anesthesiol. 2019;19(1):160. doi:10.1186/s12871-019-0829-0. PMID 31421671
12. Nahara I, Takeuchi M, Yonekura H, Takeda C, Kawakami K. Safety of sugammadex for myasthaenia gravis patients undergoing general anaesthesia: a retrospective database study. BJA Open. 2022;4:100092. doi:10.1016/j.bjao.2022.100092. PMID 37588779. PMC10430823.
13. Leventhal SR, Orkin FK, Hirsh RA. Prediction of the need for postoperative mechanical ventilation in myasthenia gravis. Anesthesiology. 1980;53(1):26–30. PMID 7386905
14. Orkin FK, Leventhal SR, Hirsh RA. Predicting respiratory failure following thymectomy. Ann N Y Acad Sci. 1981;377:862–863. doi:10.1111/j.1749-6632.1981.tb33805.x.
15. Grant RP, Jenkins LC. Prediction of the need for postoperative mechanical ventilation in myasthenia gravis: thymectomy compared to other surgical procedures. Can Anaesth Soc J. 1982;29(2):112–116. PMID 7066734
16. Min K, Choi M, Kim J. Prediction of the need for mechanical ventilation following thymectomy in myasthenia gravis. Korean J Anesthesiol. 1992;25(4):740. doi:10.4097/kjae.1992.25.4.740. Applied the Leventhal score retrospectively to 37 patients undergoing transsternal thymectomy; it was correct in 23 of 37, 62.2%, with 9 of 27 incorrectly predicted ready for extubation.
17. Leuzzi G, Meacci E, Cusumano G, et al. Thymectomy in myasthenia gravis: proposal for a predictive score of postoperative myasthenic crisis. Eur J Cardiothorac Surg. 2014;45(4):e76–e88. doi:10.1093/ejcts/ezt641. PMID 24525106
18. Kirsch JR, Diringer MN, Borel CO, Hanley DF, Merritt WT, Bulkley GB. Preoperative lumbar epidural morphine improves postoperative analgesia and ventilatory function after transsternal thymectomy in patients with myasthenia gravis. Crit Care Med. 1991;19(12):1474–1479. doi:10.1097/00003246-199112000-00006. PMID 1959365.
19. Kanai T, Uzawa A, Sato Y, et al. A clinical predictive score for postoperative myasthenic crisis. Ann Neurol. 2017;82(5):841–849. doi:10.1002/ana.25087. PMID 29083502
20. Wolfe GI, Kaminski HJ, Aban IB, et al; MGTX Study Group. Long-term effect of thymectomy plus prednisone versus prednisone alone in patients with non-thymomatous myasthenia gravis: 2-year extension of the MGTX randomised trial. Lancet Neurol. 2019;18(3):259–268. doi:10.1016/S1474-4422(18)30392-2. PMID 30692052. PMC6774753.
21. Narayanaswami P, Sanders DB, Wolfe G, et al. International consensus guidance for management of myasthenia gravis: 2020 update. Neurology. 2021;96(3):114–122. doi:10.1212/WNL.0000000000011124. PMID 33144515
22. Mouri H, Jo T, Matsui H, Fushimi K, Yasunaga H. Effect of sugammadex on postoperative myasthenic crisis in myasthenia gravis patients: propensity score analysis of a Japanese nationwide database. Anesth Analg. 2020;130(2):367–373. doi:10.1213/ANE.0000000000004239. PMID 31124838
23. Hu C, Liu S, Xi C, et al. Sugammadex versus neostigmine reversal after thoracoscopic thymectomy in myasthenia gravis: a multicenter, randomized controlled trial. Drug Des Devel Ther. 2025;19:11965–11976. doi:10.2147/DDDT.S573927. PMID 41488758. PMC12764343
24. Wolfe GI, Kaminski HJ, Aban IB, et al; MGTX Study Group. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med. 2016;375(6):511–522. doi:10.1056/NEJMoa1602489. PMID 27509100. (Erratum published 2017 regarding time-weighted prednisone dose.)
25. Polito NB, Fellows SE, Knapp AS, Acquisto NM. Evaluation of neuromuscular blocker use in myasthenia gravis patients undergoing rapid sequence intubation. Am J Emerg Med. 2026;103:21–25. doi:10.1016/j.ajem.2026.01.019
26. Myasthenia gravis. OpenAnesthesia. openanesthesia.org/keywords/myasthenia-gravis. Accessed August 2026.
27. Campos JH. Prediction of postoperative mechanical ventilation after thymectomy in patients with myasthenia gravis: a myth or reality? J Cardiothorac Vasc Anesth. 2018;32(1):331–333. doi:10.1053/j.jvca.2017.08.014. PMID 29109003
28. Chevalley C, Spiliopoulos A, de Perrot M, Tschopp JM, Licker M. Perioperative medical management and outcome following thymectomy for myasthenia gravis. Can J Anaesth. 2001;48(5):446–451. doi:10.1007/BF03028306. PMID 11394511. Source of the four accuracy figures for Leventhal’s score, all four read in the full text: sensitivity 22.2%, specificity 77.8%, positive predictive value 25% and negative predictive value 75%.
29. Huang Y, Su L, Zhang Y, Guo J, Wang C. Risk factors for postoperative myasthenic crisis after thymectomy in patients with myasthenia gravis. J Surg Res. 2021;262:1–5. doi:10.1016/j.jss.2020.12.048. PMID 33530003
30. Lee I, Kuo HC, Aban IB, et al. Minimal manifestation status and prednisone withdrawal in the MGTX trial. Neurology. 2020;95(6):e755–e766. doi:10.1212/WNL.0000000000010031. PMID 32611638
31. White MC, Stoddart PA. Anesthesia for thymectomy in children with myasthenia gravis. Paediatr Anaesth. 2004;14(8):625–635. doi:10.1111/j.1460-9592.2004.01292.x. Succinylcholine about twice the dose in adults, three to four times in children; Bell’s 10–20% of the normal atracurium dose.
32. Nilsson E, Meretoja OA. Vecuronium dose-response and maintenance requirements in patients with myasthenia gravis. Anesthesiology. 1990;73(1):28–32. doi:10.1097/00000542-199007000-00005. PMID 1972873.
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Anesthetic considerations for pulmonary hypertension

Published at /answers/anesthetic-considerations-pulmonary-hypertension.

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Anesthetic considerations for valvular heart disease

Published at /answers/anesthetic-considerations-valvular-heart-disease.

1. Thompson A, Fleischmann KE, Smilowitz NR, et al. 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2024;84(19):1869–1969. doi:10.1016/j.jacc.2024.06.013. PMID 39320289.
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8. Tai YH, Chang CC, Yeh CC, Cherng YG, Chen TL, Liao CC. Adverse outcomes after noncardiac surgery in patients with aortic stenosis. Sci Rep. 2021;11(1):19517. doi:10.1038/s41598-021-98507-6. PMID 34593867.
9. Place A, Rodrigues TS, Naimo PS, et al. Peri-operative risk of non-cardiac surgery in patients with aortic stenosis: a systematic review and meta-analysis. Anaesthesia. 2026;81(4):570–579. doi:10.1111/anae.70084. PMID 41388337.
10. Luis SA, Dohaei A, Chandrashekar P, et al. Impact of Aortic Valve Replacement for Severe Aortic Stenosis on Perioperative Outcomes Following Major Noncardiac Surgery. Mayo Clin Proc. 2020;95(4):727–737. doi:10.1016/j.mayocp.2019.10.038. PMID 32247346.
11. Okuno T, Demirel C, Tomii D, et al. Risk and Timing of Noncardiac Surgery After Transcatheter Aortic Valve Implantation. JAMA Netw Open. 2022;5(7):e2220689. doi:10.1001/jamanetworkopen.2022.20689. PMID 35797045.
12. Wilson WR, Gewitz M, Lockhart PB, et al. Prevention of Viridans Group Streptococcal Infective Endocarditis: A Scientific Statement From the American Heart Association. Circulation. 2021;143(20):e963–e978. doi:10.1161/CIR.0000000000000969. PMID 33853363.
13. Thornhill MH, Gibson TB, Yoon F, et al. Antibiotic Prophylaxis Against Infective Endocarditis Before Invasive Dental Procedures. J Am Coll Cardiol. 2022;80(11):1029–1041. doi:10.1016/j.jacc.2022.06.030. PMID 35987887.
14. Ommen SR, Ho CY, Asif IM, et al. 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2024;149(23):e1239–e1311. doi:10.1161/CIR.0000000000001250. PMID 38718139.
15. Nohria R, Romaine A, Garcia-Sampson G. Infective Endocarditis: Diagnosis and Treatment. Am Fam Physician. 2026;113(2):145–152. PMID 41839106.
16. Coisne A, Lancellotti P, Habib G, et al. ACC/AHA and ESC/EACTS Guidelines for the Management of Valvular Heart Diseases: JACC Guideline Comparison. J Am Coll Cardiol. 2023;82(8):721–734. doi:10.1016/j.jacc.2023.05.061. PMID 37587584.
17. Sarwar MF, Rodriguez-Diaz C, Dabski M, et al. Anesthesia for cardiac surgical procedures. In: Gropper MA, Eriksson LI, Fleisher LA, et al., eds. Miller’s Anesthesia. 10th ed. Elsevier; 2024:1643–1644. Source of the diastolic dysfunction and rise in LV end-diastolic pressure that follow concentric hypertrophy in aortic stenosis, and of the atrial kick contributing as much as 40% of total cardiac output.
18. Khanna S, Hargrave JM, Abraham A, et al. Anesthesia for cardiac surgery. In: Cullen BF, Stock MC, Ortega R, et al., eds. Barash, Cullen, and Stoelting’s Clinical Anesthesia. 9th ed. Wolters Kluwer; 2024: chapter 39, Table 39-8. Source of the rhythm goal in aortic stenosis: sinus, with cardioversion or rate control considered in a nonsinus rhythm.
19. Pitkänen M. Spinal (subarachnoid) blockade. In: Cousins MJ, Carr DB, Horlocker TT, Bridenbaugh PO, eds. Cousins & Bridenbaugh’s Neural Blockade in Clinical Anesthesia and Pain Medicine. 4th ed. Lippincott Williams & Wilkins; 2009:214. Source of the concern that in marked aortic stenosis the sympathetic block of spinal anesthesia can suddenly lower systemic vascular resistance and coronary perfusion, and that a limited block or a carefully titrated continuous technique can be used.
20. Wijeysundera DN, Finlayson E. Preoperative evaluation. In: Gropper MA, Eriksson LI, Fleisher LA, et al., eds. Miller’s Anesthesia. 10th ed. Elsevier; 2024:830. Source of the murmur maneuvers: standing and the Valsalva maneuver decrease preload and increase the murmur of hypertrophic cardiomyopathy, and the Valsalva maneuver decreases the murmur of aortic stenosis (Table 28.9).

Anesthetic considerations in severe COPD

Published at /answers/anesthetic-considerations-severe-copd.

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32. Berg AA, Flaherty JM, Habeck JM, Harrison AK, Braman JP, et al. Evaluation of diaphragmatic function after interscalene block with liposomal bupivacaine: a randomized controlled trial. Anesthesiology. 2022;136(4):531–541. doi:10.1097/ALN.0000000000004118. PMID 35061005.
33. Renard Y, Grape S, Gonvers E, Rossel JB, Goetti P, Albrecht E. Respiratory impact of local anaesthetic volume after interscalene brachial plexus block with extrafascial injection: a randomised controlled double-blinded trial. Br J Anaesth. 2025;134(4):1153–1160. doi:10.1016/j.bja.2024.12.010. PMID 39855930.
34. Oliver-Forniés P, Aragón-Benedí C, Gómez Gómez R, Antón Rodríguez C, et al. Hemidiaphragmatic paralysis after ultrasound-guided brachial plexus blocks for shoulder surgery: a systematic review and meta-analysis of randomized clinical trials. J Clin Anesth. 2025;105:111874. doi:10.1016/j.jclinane.2025.111874. PMID 40494113.
35. Nanda M, Auyong D. Phrenic-sparing strategies for shoulder surgery: balancing respiratory safety and block completeness. Curr Opin Anaesthesiol. 2026;39(5):641–652. doi:10.1097/ACO.0000000000001682. PMID 42406517.
36. Spasari E, Cirillo D, Sepolvere G, Ranieri G, Santonastaso D, et al. Regional anesthesia strategies for proximal humerus fracture surgery: anatomical considerations, diaphragm-sparing techniques, and expert perspectives: a narrative review. Langenbecks Arch Surg. 2026;411(1):119. doi:10.1007/s00423-026-03980-0. PMID 41787124.
37. Hong B, Lee S, Oh C, Park S, Rhim H, et al. Hemidiaphragmatic paralysis following costoclavicular versus supraclavicular brachial plexus block: a randomized controlled trial. Sci Rep. 2021;11(1):18749. doi:10.1038/s41598-021-97843-x. PMID 34548555.
38. Ahmadzadeh S, Naccari BP, Amedio LS, Koruna AE, Bass D, et al. Efficacy of suprascapular versus interscalene block for post-operative pain management in shoulder surgeries: a narrative review. Curr Pain Headache Rep. 2026;30(1):13 (published online 29 Dec 2025). doi:10.1007/s11916-025-01443-7. PMID 41457137.
39. Shinn HK, Kim BG, Jung JK, Kwon HU, Yang C, Won J. Prolonged hemidiaphragmatic paresis following continuous interscalene brachial plexus block: a case report. Medicine (Baltimore). 2016;95(24):e3891. doi:10.1097/MD.0000000000003891. PMID 27310984.
40. Merck Sharp & Dohme LLC. BRIDION (sugammadex) injection, prescribing information (Indications and Usage). Revised 3/2026. DailyMed setid 5171d883-fe8f-482c-97ab-40b00975b64a. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5171d883-fe8f-482c-97ab-40b00975b64a.
41. Par Health USA, LLC. KETALAR (ketamine hydrochloride) injection, prescribing information (Dosage and Administration). Revised 3/2026. DailyMed setid 14e8f864-8b8a-4e7e-8439-e510d3107063. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14e8f864-8b8a-4e7e-8439-e510d3107063.
42. Hospira, Inc. AMIDATE (etomidate) injection, prescribing information (Dosage and Administration). Revised 04/2022. DailyMed setid b7ed5bf8-ba75-44dc-8f81-96b4ad5766be. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b7ed5bf8-ba75-44dc-8f81-96b4ad5766be.

Buprenorphine and surgery: continue, don’t hold

Published at /answers/buprenorphine-perioperative-management.

1. Kohan L, Potru S, Barreveld AM, et al. Buprenorphine management in the perioperative period: educational review and recommendations from a multisociety expert panel. Reg Anesth Pain Med. 2021;46(10):840–859. doi:10.1136/rapm-2021-103007. PMID 34385292.
2. American Society of Addiction Medicine. The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 focused update. J Addict Med. 2020;14(2S Suppl 1):1–91. doi:10.1097/ADM.0000000000000633. PMID 32511106. Discontinuation before surgery is not required; dose decisions are individualized with the addiction treatment provider, and temporarily increasing the dose or dosing frequency (split dosing) may help manage pain.
3. Goel A, Azargive S, Weissman JS, et al. Perioperative Pain and Addiction Interdisciplinary Network (PAIN) clinical practice advisory for perioperative management of buprenorphine: results of a modified Delphi process. Br J Anaesth. 2019;123(2):e333–e342. PMC6676043.
4. Selvamani BJ, Kral L, Swaran Singh T. Perioperative management of patients on buprenorphine for opioid use disorder. ASRA News. February 2023;48(1). doi:10.52211/asra020123.010. Summarizes the 2021 multisociety panel, the 2018 SAMHSA update, and systematic reviews finding no evidence favoring discontinuation, especially below 16 mg daily.
5. Hitt JM, Elkin PL, de Leon-Casasola OA. Continuation versus interruption of buprenorphine/naloxone in adult veterans undergoing surgery: examination of postoperative pain and opioid utilization in a national retrospective cohort study. Anesthesiology. 2025;142(2):320–331. doi:10.1097/ALN.0000000000005291. PMID 39527644. PMC11732713. Retrospective cohort, 1,881 surgical cases in 1,673 patients. Supplemental opioid 74.2 mg morphine equivalents per day with interruption versus 39.7 with continuation.
6. Harin E, Ashok V, Andereggen L, Urman RD, Luedi MM. An individualized, interdisciplinary approach to the perioperative care of patients on buprenorphine. Curr Pain Headache Rep. 2026. doi:10.1007/s11916-026-01545-w. PMID 42581132. PMC13461782.
7. Desai A, Parikh S, Bergese S. Perioperative buprenorphine management and postoperative pain outcomes: a retrospective study with evidence-based recommendations. Int J Transl Med. 2024;4(3):539–546. doi:10.3390/ijtm4030036. Describes the origin of the discontinuation practice in case reports of undertreated pain.
8. Vadivelu N, Mydlo N, Dextras C, et al. Perioperative management of patients on buprenorphine. Curr Pain Headache Rep. 2026. doi:10.1007/s11916-025-01432-w
9. Champagne K, Date P, Forero JP, Arany J, Gritsenko K. Patients on buprenorphine formulations undergoing surgery. Curr Pain Headache Rep. 2022;26(6):459–468. doi:10.1007/s11916-022-01046-6. PMID 35460492.
10. Wyse JJ, et al. Perioperative management of buprenorphine/naloxone in a large, national health care system: a retrospective cohort study. J Gen Intern Med. 2021. doi:10.1007/s11606-021-07118-4. Describes dose-splitting above 16 mg, care coordination for reinitiation, and low-dose induction.
11. Gibbons JB, McCullough JS, Zivin K, Brown ZY, Norton EC. Association between buprenorphine treatment gaps, opioid overdose, and health care spending in US Medicare beneficiaries with opioid use disorder. JAMA Psychiatry. 2022;79(12):1173–1179. doi:10.1001/jamapsychiatry.2022.3118. PMC9535497. Opioid overdose was 2.89 times as likely in treatment-gap months as in treated months.
12. Perioperative pain management guidance for patients on chronic buprenorphine. US Department of Veterans Affairs, February 2022. va.gov/formularyadvisor/DOC_PDF/CRE_Buprenorphine_Perioperative_Guidance_FEB2022.pdf. Notes that a clinically significant proportion of receptors remain available even at high stable doses, and that this finding drove the change in expert consensus.
13. Guidelines for the perioperative management of buprenorphine. US Department of Veterans Affairs, February 2022. va.gov/formularyadvisor/DOC_PDF/CRE_Periop_BUPRENORPHINE_Algorithm_FEB2022.pdf. Multimodal strategy including regional catheters, ketamine, lidocaine, gabapentinoids, acetaminophen and NSAIDs.
14. Quaye A, Potter K, Roth S, Acampora G, Mao J, Zhang Y. Perioperative continuation of buprenorphine at low-moderate doses was associated with lower postoperative pain scores and decreased outpatient opioid dispensing compared with buprenorphine discontinuation. Pain Med. 2020;21(9):1955–1960. doi:10.1093/pm/pnaa020. PMID 32167541. Retrospective single-center comparison of 55 surgical patients, 38 continued against 17 held: PACU pain scores 2.9 versus 7.6, and mean morphine equivalents dispensed 229 versus 521.
15. Davis MP, Pasternak G, Behm B. Treating chronic pain: an overview of clinical studies centered on the buprenorphine option. Drugs. 2018;78(12):1211–1228. doi:10.1007/s40265-018-0953-z. CNS clearance slower than plasma clearance; receptor occupancy after a single 16 mg sublingual dose.
16. Suboxone (buprenorphine and naloxone) sublingual film. Prescribing information. DailyMed, US National Library of Medicine; updated December 2025. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8a5edcf9-828c-4f97-b671-268ab13a8ecd. Higher-than-normal doses and repeated administration of naloxone may be necessary.
17. American College of Obstetricians and Gynecologists, Committee on Obstetric Practice. Committee Opinion No. 711: opioid use and opioid use disorder in pregnancy. Obstet Gynecol. 2017;130(2):e81–e94. doi:10.1097/AOG.0000000000002235.
18. Kozińska RB, Ślęzak J, Ilski I, et al. Can buprenorphine be overdosed? The ceiling effect and its clinical implications. Pharmaceuticals (Basel). 2026;19(6):903. doi:10.3390/ph19060903. PMID 42356521.
19. Funk MC, Nash S, Smith A, et al. Treatment of opioid use disorder in the general hospital. Am J Psychiatry. 2023;180(8):594–596. doi:10.1176/appi.ajp.23180008. American Psychiatric Association resource document, approved 2022.
20. Saari TI, Strang J, Dale O. Clinical pharmacokinetics and pharmacodynamics of naloxone. Clin Pharmacokinet. 2024;63(4):397–422. doi:10.1007/s40262-024-01355-6.
21. Englander H, Thakrar AP, Bagley SM, et al. Caring for hospitalized adults with opioid use disorder in the era of fentanyl: a review. JAMA Intern Med. 2024;184(6):691–701. doi:10.1001/jamainternmed.2023.7282.

Further reading, not cited in the text:

• Anderson TA, Quaye ANA, Ward EN, Wilens TE, Hilliard PE, Brummett CM. To stop or not, that is the question: acute pain management for the patient on chronic buprenorphine. Anesthesiology. 2017;126(6):1180–1186.

CABG anesthesia, step by step

Published at /answers/cabg-anesthesia-step-by-step.

1. Myles PS, Smith JA, Forbes A, et al; ATACAS Investigators of the ANZCA Clinical Trials Network. Tranexamic acid in patients undergoing coronary-artery surgery. N Engl J Med. 2017;376(2):136–148. doi:10.1056/NEJMoa1606424. 4,631 patients in the tranexamic acid comparison (2,311 versus 2,320). Aspirin arm reported separately: Myles PS, et al. Stopping vs. continuing aspirin before coronary artery surgery. N Engl J Med. 2016;374:728–737.
2. Cartwright B, Mundell N. Anticoagulation for cardiopulmonary bypass: part one. BJA Educ. 2023;23(3):110–116. doi:10.1016/j.bjae.2022.12.003. PMID 36844440. PMC9947996. Heparin dosing, heparin resistance definition and causes.
3. Shore-Lesserson L, Baker RA, Ferraris VA, et al. The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the American Society of ExtraCorporeal Technology: clinical practice guidelines — anticoagulation during cardiopulmonary bypass. Ann Thorac Surg. 2018;105(2):650–662. doi:10.1016/j.athoracsur.2017.09.061. PMID 29362176.
4. Cardiopulmonary bypass: anticoagulation and antagonism. OpenAnesthesia. openanesthesia.org/keywords/cardiopulmonary-bypass-anticoagulation-and-antagonism. Accessed August 2026. ACT targets, factors influencing ACT, heparinase assays.
5. Levy JH, Sniecinski RM, Maier CL, et al. Finding a common definition of heparin resistance in adult cardiac surgery: communication from the ISTH SSC subcommittee on perioperative and critical care thrombosis and hemostasis. J Thromb Haemost. 2024;22(4):1249–1257. doi:10.1016/j.jtha.2024.01.001. PMID 38215912. Proposes ACT below 480 s after 500 U/kg as the standardized definition.
6. Boer C, Meesters MI, Veerhoek D, et al. Anticoagulant and side-effects of protamine in cardiac surgery: a narrative review. Br J Anaesth. 2018;120(5):914–927. doi:10.1016/j.bja.2018.01.023. PMID 29661409.
7. Lamy A, Sirota DA, Jacques F, Poostizadeh A, Noiseux N, Efremov S, et al. Topical versus intravenous tranexamic acid in patients undergoing cardiac surgery: the DEPOSITION randomized controlled trial. Circulation. 2024. doi:10.1161/CIRCULATIONAHA.124.069606. 3,242 patients, 16 hospitals, 6 countries; stopped early; topical produced an 8.3% absolute increase in transfusion without reducing seizures. Cites the STS class IA recommendation for intravenous tranexamic acid.
8. Roebker J, Deghan S. Tranexamic acid reduces bleeding risk during coronary artery surgery: the ATACAS trial. 2 Minute Medicine, 11 January 2017. 2minutemedicine.com. Trial summary noting the mid-trial dose reduction from 100 mg/kg to 50 mg/kg and the underpowered dose comparison.
9. Takagi H, Ando T, Umemoto T. Seizures associated with tranexamic acid for cardiac surgery: a meta-analysis of randomized and non-randomized studies. J Cardiovasc Surg (Torino). 2017. PMID 28263046. Sixteen studies, 45,235 patients; odds ratio 4.13 (95% CI 2.59–6.57), P < 0.00001.
10. Myles PS, Smith JA, Forbes A, et al. Tranexamic acid in coronary artery surgery: one-year results of the ATACAS trial. J Thorac Cardiovasc Surg. 2019;157(2):644–652. PMID 30459103. Death or disability at one year 3.8% versus 4.4%.
11. Guo J, Gao X, Ma Y, et al. Different dose regimes and administration methods of tranexamic acid in cardiac surgery: a meta-analysis of randomized trials. BMC Anesthesiol. 2019;19:129. doi:10.1186/s12871-019-0772-0. Forty-nine studies, 10,591 patients.
12. International Society of Blood Transfusion. Antifibrinolytic agent — tranexamic acid. Patient blood management resources, Clinical Transfusion Working Party. Zolfaghari S, van Kraaij M; revised by Zolfaghari S, Relke N. Updated January 2026. isbtweb.org/isbt-working-parties/clinical-transfusion/resources/patient-blood-management-resources/3-tranexamic-acid.html. Notes dose-dependent seizure risk above 2 g/day and summarizes the OPTIMAL trial.
13. Chen Y, Phoon PHY, Hwang NC. Heparin resistance during cardiopulmonary bypass in adult cardiac surgery. J Cardiothorac Vasc Anesth. 2022;36(11):4150–4160. doi:10.1053/j.jvca.2022.06.021. PMID 35927191. PMC9225936. Incidence 4–26%; survey data on practice variation.
14. Sabe SA, Harris DD, Broadwin M, Sellke FW. Cardioprotection in cardiovascular surgery. Basic Res Cardiol. 2024;119(4):545–568. doi:10.1007/s00395-024-01062-0. Cardioplegia strategies, blood vs crystalloid, antegrade/retrograde delivery.
15. Chatterjee S, Ortoleva J, Arora RC, et al. Management algorithm for vasoplegic shock after cardiac surgery: an interdisciplinary collaboration. Ann Thorac Surg. 2026. doi:10.1016/j.athoracsur.2026.06.013. Incidence 5–50%; risk factors; norepinephrine, early vasopressin, then angiotensin II; adjuncts for refractory cases.
16. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022. doi:10.1016/j.jacc.2021.09.006. PMID 34895950. Anesthetic maintenance technique and mortality.
17. Datt V, Wadhhwa R, Sharma V, et al. Vasoplegic syndrome after cardiovascular surgery: a review of pathophysiology and outcome-oriented therapeutic management. J Card Surg. 2021;36(10):3749–3760. doi:10.1111/jocs.15805.
18. Ltaief Z, Ben-Hamouda N, Rancati V, et al. Vasoplegic syndrome after cardiopulmonary bypass in cardiovascular surgery: pathophysiology and management in critical care. J Clin Med. 2022;11(21):6407. doi:10.3390/jcm11216407. PMID 36362635.
19. Viaro F, Dalio MB, Evora PR. Catastrophic cardiovascular adverse reactions to protamine are nitric oxide/cyclic guanosine monophosphate dependent and endothelium mediated: should methylene blue be the treatment of choice? Chest. 2002;122(3):1061–1066. doi:10.1378/chest.122.3.1061. PMID 12226053.
20. Lanoiselée J, Gibert A, Gouin-Thibault I, et al. Optimising protamine dosing for heparin reversal after cardiopulmonary bypass: a population pharmacokinetic–pharmacodynamic study. Br J Anaesth. 2026;136(3):847–855. PMID 41638976. 68 patients; simulations predicted a 0.625:1 ratio would fully reverse heparin in 95%.
21. Taneja R, Szoke DJ, Hynes Z, Jones PM. Minimum protamine dose required to neutralize heparin in cardiac surgery: a single-centre, prospective, observational cohort study. Can J Anaesth. 2023;70(2):219–227. doi:10.1007/s12630-022-02364-4. PMID 36471142. A 0.5:1 ratio neutralized residual anti-IIa and anti-Xa activity in most patients.
22. Jain P, Silva-De Las Salas A, Bedi K, et al. Protamine dosing for heparin reversal after cardiopulmonary bypass: a double-blinded prospective randomized control trial comparing two strategies. Anesthesiology. 2025;142:98–106. doi:10.1097/ALN.0000000000005256. PMID 39388600. Fixed 250 mg dose vs weight-based 1:1.
23. Phothikun A, Nawarawong W, Tantraworasin A, Phinyo P, Tepsuwan T. The outcomes of three different techniques of coronary artery bypass grafting: on-pump arrested heart, on-pump beating heart, and off-pump. PLoS One. 2023;18(5):e0286510. doi:10.1371/journal.pone.0286510. PMID 37256890. PMC10231783.
24. Landoni G, Lomivorotov VV, Nigro Neto C, et al. Volatile anesthetics versus total intravenous anesthesia for cardiac surgery. N Engl J Med. 2019;380(13):1214–1225. doi:10.1056/NEJMoa1816476. The MYRIAD trial.
25. Jiao XF, Lin XM, Ni XF, et al. Volatile anesthetics versus total intravenous anesthesia in patients undergoing coronary artery bypass grafting: an updated meta-analysis and trial sequential analysis of randomized controlled trials. PLoS One. 2019;14(10):e0224562. doi:10.1371/journal.pone.0224562. PMID 31661512.
26. Pufulete M, Reeves B, Rogers C, et al. Warm versus cold blood, and any blood versus crystalloid, cardioplegia in adults undergoing coronary artery bypass grafting surgery with cardiopulmonary bypass. Cochrane Database Syst Rev. 2013. doi:10.1002/14651858.CD010650. Carries Buckberg’s figure of about 90% less myocardial oxygen consumption at arrest.
27. Bakaeen FG, Gaudino M, Whitman G, et al. 2021: The American Association for Thoracic Surgery expert consensus document: coronary artery bypass grafting in patients with ischemic cardiomyopathy and heart failure. J Thorac Cardiovasc Surg. 2021;162(3):829–850.e1. doi:10.1016/j.jtcvs.2021.04.052.
28. Guru V, Omura J, Alghamdi AA, Weisel R, Fremes SE. Is blood superior to crystalloid cardioplegia? A meta-analysis of randomized clinical trials. Circulation. 2006;114(1 Suppl):I331–I338. doi:10.1161/CIRCULATIONAHA.105.001644. PMID 16820596.
29. Guarracino F, Habicher M, Treskatsch S, et al. Vasopressor therapy in cardiac surgery — an experts’ consensus statement. J Cardiothorac Vasc Anesth. 2021;35(4):1018–1029. doi:10.1053/j.jvca.2020.11.032. PMID 33334651. GRADE/Delphi consensus: norepinephrine and/or vasopressin (strong); vasopressin in pulmonary hypertension or right-sided dysfunction, and to prevent atrial arrhythmias (weak); methylene blue only as rescue and no dopamine (strong); angiotensin II (insufficient evidence).

Cannabis and anesthesia: what you should tell us

Published at /answers/cannabis-and-anesthesia.

1. Shah S, Schwenk ES, Sondekoppam RV, et al. ASRA Pain Medicine consensus guidelines on the management of the perioperative patient on cannabis and cannabinoids. Reg Anesth Pain Med. 2023;48(3):97–117. doi:10.1136/rapm-2022-104013. PMID 36596580.
2. All patients should be screened for cannabis use before surgery, first US guidelines recommend. ASRA Pain Medicine, 3 January 2023. asra.com/news-publications/asra-update-item/asra-updates/2023/01/03/all-patients-should-be-screened-for-cannabis-use-before-surgery-first-u.s.-guidelines-recommend. Describes the 13-expert panel, modified Delphi with >75% agreement, 21 recommendations, all achieving full consensus.
3. ASRA guidelines recommend screening patients for cannabis use before surgery. MedCentral, 22 February 2023. medcentral.com/meds/cannabinoids/asra-guidelines-recommend-screening-patients-for-cannabis-use-before-surgery. Summary of the 2023 guideline, including the recommendation against universal toxicology screening and in favor of the Cannabis Use Disorder Identification Test.
4. Perioperative care considerations for patients with cannabis use. Cannabis Evidence, US Department of Veterans Affairs and Oregon Health & Science University, November 2023. cannabisevidence.org/clinician-resources/clinician-briefs/perioperative-care. Clinician brief summarizing ASRA recommendations, acute intoxication features, and the prospective study of postoperative pain outcomes. Its respiratory section covers smoke toxins, obstructive pathology and reduced FEV1/FVC; the airway hyperreactivity claim on this page is sourced to reference 12 instead.
5. ASRA guidelines for the perioperative patient on cannabis and cannabinoids — guideline summary. Guideline Central, summarizing the 2023 consensus guideline at reference 1. guidelinecentral.com/guideline/2397689. Includes the Grade C dose-adjustment recommendation, the EEG monitoring statement, and the pregnancy recommendations.
6. Baker MB, Binda DD, Nozari A, Kennedy JM, Dienes E, Baker WE. Quantitative analysis of propofol dosage in cannabis users: a systematic review and meta-analysis. J Clin Med. 2025;14(3):858. doi:10.3390/jcm14030858. PMID 39941531. PMC11818839. Random-effects model throughout. Eight studies, 2,268 patients; +47.33 mg overall, +30.57 mg for general anesthesia (95% CI 4.79 to 56.34), +53.02 mg for endoscopic sedation (95% CI 25.02 to 81.02). The results section states that under a random effects model the differences in the subgroups were not statistically significant (p = 0.25).
7. Irvine D, Meyer T, Thornton I, Huang J. Cannabis and anesthesia: a 2025 update on perioperative considerations. APSF Newsletter. 2026;1:9–12. Anesthesia Patient Safety Foundation. apsf.org/article/cannabis-and-anesthesia-a-2025-update-on-perioperative-considerations. Summarizes two meta-analyses (2,268 and 4,199 patients) and inhalational agent requirements. Legalization figures are stated as of mid-2025 and sourced to the National Conference of State Legislatures.
8. Echeverria-Villalobos M, Fabian CA, Mitchell JG, et al. Cannabinoids and general anesthetics: revisiting molecular mechanisms of their pharmacological interactions. Anesth Analg. 2025;140(6):1401–1413. doi:10.1213/ANE.0000000000007313. PMID 39504269. PMC12063680. Notes consistently increased requirements for GABAergic agents in humans alongside divergent animal findings.
9. Flisberg P, Paech MJ, Shah T, Ledowski T, Kurowski I, Parsons R. Induction dose of propofol in patients using cannabis. Eur J Anaesthesiol. 2009;26(3):192–195. doi:10.1097/EJA.0b013e328319be59. PMID 19237981. Randomized, single-blind study of propofol requirement for laryngeal mask airway insertion in regular cannabis users versus non-users, as summarized in perioperative clinician guidance.
10. Sajdeya R, Treggiari MM, Narouze S. Review of cannabis use and propofol anesthesia: recent insights and clinical implications. Curr Opin Anaesthesiol. 2025. PMID 40583839. States that no evidence currently supports causality and mechanisms remain unknown.
11. Perioperative considerations for the patient utilizing cannabis. Iowa Department of Health and Human Services. Published as “Perioperative considerations for the patient utilizing cannabinoid-based medicines and products.” hhs.iowa.gov/media/9136/download. Covers THC catecholamine and dysrhythmia effects. (Note: this brief also states synthetic-cannabinoid coagulopathy is not corrected by vitamin K or FFP; that statement is superseded on this page by references 15–17.)
12. Goudra B, Green M. Perioperative repercussions of cannabis use — implications for GI endoscopy sedation. J Clin Med. 2025;14(19):7028. doi:10.3390/jcm14197028. PMC12525429. Source of the Bornemann-Cimenti pooled figures quoted above, and of the endoscopy sedation literature.
13. Canadian Cannabis Survey 2024. Health Canada. canada.ca/en/health-canada/services/drugs-medication/cannabis/research-data/canadian-cannabis-survey-2024-summary.html. Past 12-month cannabis use among Canadians aged 16 and older was 26% in 2024, unchanged from 2023 and up from 22% in 2018.
14. Hasckel Gewehr JL, Enzele ML, Freiria LM, et al. Full spectrum cannabidiol-rich extract reduced propofol dosage required for anesthetic induction in dogs — a pilot study. Front Vet Sci. 2024;11:1352314. doi:10.3389/fvets.2024.1352314. PMID 38645644. Twenty-seven healthy client-owned dogs in three groups of nine; 6 mg/kg of total phytocannabinoids transmucosally reduced the propofol induction dose by 23% against olive-oil control, with no significant sedation. The authors describe it as a pilot and call for confirmation.
15. Connors JM. Hemorrhagic highs from synthetic cannabinoids — a new epidemic. N Engl J Med. 2018;379(13):1275–1277. Editorial describing the brodifacoum-contaminated synthetic cannabinoid coagulopathy and its treatment with high-dose vitamin K.
16. Kelkar AH, Smith NA, Martial A, et al. An outbreak of synthetic cannabinoid–associated coagulopathy in Illinois. N Engl J Med. 2018;379(13):1216–1223. Case series in which INR corrected with high-dose vitamin K1; FFP gave only transient correction.
17. Bahouth MN, Kraus P, Dane K, et al. Synthetic cannabinoid-associated coagulopathy secondary to long-acting anticoagulant rodenticides: observational case series and management recommendations. Medicine (Baltimore). 2019;98(36):e17015. Recommends prolonged high-dose oral vitamin K1; FFP/PCC reserved for active bleeding only. Confirms vitamin K reverses the coagulopathy. doi:10.1097/MD.0000000000017015. PMID 31490385.
18. King DD, Temmermand R, Greenwood JE. Preoperative cannabinoid exposure and postoperative pain: a narrative review. J Clin Anesth. 2026. Narrative review of 42 studies; approximately one-third reported higher postoperative pain and roughly 43% higher opioid use, with a substantial minority showing no difference, and outcomes varying by surgical specialty.
19. Bicket MC, Ladha KS, Boehnke KF, et al. The association of cannabis use after discharge from surgery with opioid consumption and patient-reported outcomes. Ann Surg. 2024. Cohort in which cannabis users reported worse pain scores but consumed only approximately one additional opioid pill, of uncertain clinical significance.
20. Mims MM, Parikh AC, Sandhu Z, et al. Surgery-related considerations in treating people who use cannabis: a review. JAMA Otolaryngol Head Neck Surg. 2024. Describes cannabis withdrawal syndrome, suggests abstaining from midnight before surgery as a practical compromise, and cautions against rapid tapers in the week before surgery.
21. Cummings KC, Keshock M, Ganesh R, et al. Preoperative management of surgical patients using dietary supplements: Society for Perioperative Assessment and Quality Improvement (SPAQI) consensus statement. Mayo Clin Proc. 2021;96(5):1342–1355. Recommends abstaining from cannabis a minimum of 3 days (ideally up to 2 weeks) to reduce airway irritability, and notes coronary vasospasm as a cardiovascular risk.

Clopidogrel hold time before neuraxial and pain procedures

Published at /answers/clopidogrel-hold-time-before-neuraxial-and-pain-procedures.

1. Narouze S, Benzon HT, Provenzano D, Buvanendran A, De Andres J, Deer T, Rauck R, Huntoon MA. Interventional spine and pain procedures in patients on antiplatelet and anticoagulant medications (second edition): guidelines from the American Society of Regional Anesthesia and Pain Medicine, the European Society of Regional Anaesthesia and Pain Therapy, the American Academy of Pain Medicine, the International Neuromodulation Society, the North American Neuromodulation Society, and the World Institute of Pain. Reg Anesth Pain Med. 2018;43(3):225–262. doi:10.1097/AAP.0000000000000700. PMID 29278603
2. Kopp SL, Vandermeulen E, McBane RD, Perlas A, Leffert L, Horlocker T. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (fifth edition). Reg Anesth Pain Med. Published online 29 January 2025. doi:10.1136/rapm-2024-105766. PMID 39880411
3. ASRA Guidelines for Regional Anesthesia with Antithrombotic or Thrombolytic Therapy, 5th edition — guideline summary. Guideline Central, summarizing the guideline at reference 2. guidelinecentral.com/guideline/4293939. Tabulates the P2Y12 intervals and recommendation grades quoted above.
4. Updated guidance on anesthesia with antithrombotic/thrombolytic therapy. Medscape, 7 February 2025. medscape.com/viewarticle/updated-guidance-anesthesia-antithrombotic-thrombolytic-2025a1000339. Media briefing remarks by lead author Sandra Kopp, MD, describing the two principal changes in the fifth edition.
5. The drug-level thresholds for apixaban, rivaroxaban and edoxaban, and for low molecular weight heparin, are from the fifth-edition guideline itself at reference 2.
6. ASRA Pain Medicine anticoagulation problem-based learning discussion: regional anesthesia and pain procedures in anticoagulated patients. ASRA Pain Medicine, 1 September 2025. asra.com/news-publications/asra-updates/blog-landing/legacy-b-blog-posts/2025/09/01/asra-pain-medicine-anticoagulation-pbld---regional-anesthesia-and-pain-procedures-in-anticoagulated-patients. Describes the rationale for classifying SCS trial and implant as high risk.
7. Perioperative management of antiplatelet and anticoagulant therapy in patients undergoing interventional techniques: 2024 updated guidelines from the American Society of Interventional Pain Physicians (ASIPP). Pain Physician. 2024;27(S6):S1–S94. doi:10.36076/ppj.2024.7.s1.
8. Updates to the ASRA guidelines for interventional pain procedures. ASRA News, 27 August 2019. asra.com/news-publications/asra-newsletter/newsletter-item/asra-news/2019/08/27/updates-to-the-asra-guidelines-for-interventional-pain-procedures. Summarizing restart intervals from the second-edition interventional guideline.
9. FactFinders for patient safety: antithrombotics and interventional pain procedures — lumbar transforaminal epidural steroid injections and lumbar medial branch radiofrequency neurotomy. Spine Intervention Society Patient Safety Committee. Interv Pain Med. 2022. PMC11411602
10. Safety profile of cervical transforaminal epidural steroid injections performed while maintaining anticoagulation, aspirin, or NSAIDs. Interv Pain Med. 2025. PMC12486170. Summarizing prior series by Furman and colleagues and a prospective series of cervical epidural injections on clopidogrel, warfarin, or aspirin.
11. Kopp SL, et al., fifth edition, as at reference 2. Reg Anesth Pain Med. Published online 29 January 2025. doi:10.1136/rapm-2024-105766. PMID 39880411. On the methodological limits of the evidence base — the rarity of spinal hematoma precludes a prospective randomized study and no laboratory model exists.
12. Douketis JD, Spyropoulos AC, Murad MH, et al. Perioperative management of antithrombotic therapy: an American College of Chest Physicians clinical practice guideline. Chest. 2022;162(5):e207–e243. Recommends stopping clopidogrel approximately 5 days before surgery.
13. Kumbhani DJ, Gibson CM, Kinlay S, et al. Antiplatelet therapy in the management of atherosclerotic cardiovascular disease: 2026 ACC scientific statement: a report of the American College of Cardiology. J Am Coll Cardiol. 2026. Recommends discontinuing clopidogrel 5 days before surgery.
14. Plavix (clopidogrel) prescribing information. Food and Drug Administration, 2025. Steady-state inhibition of platelet aggregation of approximately 40–60% with 75 mg daily; platelet aggregation and bleeding time return toward baseline generally about 5 days after discontinuation; reduced platelet inhibition in renal impairment.
15. Schilling U, Dingemanse J, Ufer M. Pharmacokinetics and pharmacodynamics of approved and investigational P2Y12 receptor antagonists. Clin Pharmacokinet. 2020;59(5):545–566. Up to approximately 40% of patients respond poorly to clopidogrel, largely from insufficient active-metabolite generation, drug interactions, and CYP2C19 polymorphism.
16. Douketis JD, Spyropoulos AC, Murad MH, et al. Perioperative management of antithrombotic therapy: an American College of Chest Physicians clinical practice guideline. Chest. 2022;162(5):e207–e243; and Keeling D, Tait RC, Watson H. Peri-operative management of anticoagulation and antiplatelet therapy. Br J Haematol. 2016;175(4):602–613. Low-dose aspirin is generally continued through neuraxial and interventional procedures.
17. Manchikanti L, Kaye AD, Nampiaparampil DE, et al. Perioperative management of patients receiving interventional techniques and antiplatelet and anticoagulant therapy: a balancing act. Curr Pain Headache Rep. 2025;29(1):107. doi:10.1007/s11916-025-01405-z. Narrative review; tabulates clopidogrel and prasugrel at 5 days for intermediate/moderate risk and 6 days for high risk.
18. Manchikanti L, Abd-Elsayed A, Kaye AD, et al. Review of guidelines for implantable peripheral nerve stimulation (PNS) in the management of chronic pain. Curr Pain Headache Rep. 2025;29(1):89. doi:10.1007/s11916-025-01397-w. Carries the same 5-day intermediate-risk table.

Cricoid pressure: does it actually work?

Published at /answers/cricoid-pressure-evidence.

1. Birenbaum A, Hajage D, Roche S, et al; IRIS Investigators Group. Effect of cricoid pressure compared with a sham procedure in the rapid sequence induction of anesthesia: the IRIS randomized clinical trial. JAMA Surg. 2019;154(1):9–17. doi:10.1001/jamasurg.2018.3577. PMID 30347104. ClinicalTrials.gov NCT02080754.
2. Cricoid pressure in airway management: the IRIS trial. REBEL EM, 15 November 2018. rebelem.com/cricoid-pressure-in-airway-management-the-iris-trial. Covers the trial design, the sham technique, and the historical origin of the maneuver including the pre-Sellick descriptions and the methodological flaws of the initial studies.
3. JC: cricoid pressure and RSI, do we still need it? St Emlyn’s, 20 October 2018. stemlynsblog.org/jc-cricoid-pressure-and-rsi-do-we-still-need-it-st-emlyns. Sets out the power calculation problem — recruitment targets based on an estimated 2.8% aspiration prevalence against a far lower observed rate. The operator training protocol is in the trial report itself, reference 1, not here.
4. Bermede O, Meço BC, Baytaş V, et al. What about compressing the oesophagus with an ultrasound probe for a modified Sellick maneuver? Turk J Anaesthesiol Reanim. 2022. doi:10.5152/TJAR.2021.1427. One hundred ten volunteers; esophageal position relative to the cricoid ring.
5. Kim HY, Moon JH, Park HY, Min SK, Kim JY. A noninferiority trial comparing left paratracheal pressure versus cricoid pressure on tracheal intubation conditions using the Pentax Airway Scope. Sci Rep. 2022;12:16299. doi:10.1038/s41598-022-20681-y
6. White L, Thang C, Hodsdon A, Melhuish T, Vlok R. Cricoid pressure during intubation: a systematic review and meta-analysis of randomised controlled trials. Heart Lung. 2019. doi:10.1016/j.hrtlng.2019.10.001
7. Systematic review and meta-analysis of cricoid pressure training and education efficacy. PMID 29851051. Eight eligible studies; training improves accuracy of applied force.
8. Validation of a novel handheld device for accurate cricoid pressure in healthy volunteers. ClinicalTrials.gov NCT06540625. University Health Network, Toronto. Describes the force inconsistency problem motivating device development.
9. Ben-Naoui I, Compère V, Clavier T, Besnier E. Practices of rapid sequence induction for prevention of aspiration — an international declarative survey. J Clin Med. 2025;14(7):2177. doi:10.3390/jcm14072177. PMID 40217627. PMC11989417. International declarative survey of rapid sequence induction practice across the ESAIC network. 491 respondents in 61 countries; Sellick maneuver used by 42%. See also the accompanying IRIS editorial for guideline direction: Tisherman SA, Anders MG, Galvagno SM. Is 30 Newtons of prevention worth a pound of a cure?—cricoid pressure. JAMA Surg. 2019.
10. Khorasani A, Salem MR, Crystal GJ. Utility of cricoid pressure (letter). JAMA Surg. 2019. Critique of IRIS power/event-rate assumptions and the sample size that a real-world event rate would require.
11. Sun CK, Chang YJ, Hung KC. Utility of cricoid pressure (letter). JAMA Surg. 2019. Raises the second-attempt regurgitation scenario when cricoid pressure is released for interposed bag-mask ventilation.
12. Smith KJ, Dobranowski J, Yip G, Dauphin A, Choi PT. Cricoid pressure displaces the esophagus: an observational study using magnetic resonance imaging. Anesthesiology. 2003. Lateral esophageal displacement in ~90% once cricoid pressure is applied.
13. Smith KJ, Ladak S, Choi PT, Dobranowski J. The cricoid cartilage and the esophagus are not aligned in close to half of adult patients. Can J Anaesth. 2002.
14. Sotiriou A, Ahmad I, El-Boghdadly K. Cricoid force: anatomic, physiologic, and clinical concepts. Anesthesiology. 2025. Postcricoid hypopharyngeal compression mechanism; limited effect of cricoid force on intubation success with videolaryngoscopy.
15. Hung KC, Hung CT, Poon YY, et al. The effect of cricoid pressure on tracheal intubation in adult patients: a systematic review and meta-analysis. Can J Anaesth. 2021. No significant difference in poor laryngoscopic views (RR ~1.49, p = 0.21).
16. Kim H, Chang JE, Won D, et al. Effectiveness of cricoid and paratracheal pressures in occluding the upper esophagus through induction of anesthesia and videolaryngoscopy: a randomized, crossover study. Anesth Analg. 2022. Cricoid occluded the esophagus in 100% versus 58% for paratracheal pressure.
17. Noll E, Shodhan S, Varshney A, et al. Trainability of cricoid pressure force application: a simulation-based study. Anesth Analg. 2019.
18. Lasa JJ, Dhillon GS, Duff JP, et al. Part 8: pediatric advanced life support: 2025 American Heart Association and American Academy of Pediatrics guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2025.
19. Sajayan A, Wicker J, Ungureanu N, Mendonca C, Kimani PK. Current practice of rapid sequence induction of anaesthesia in the UK — a national survey. Br J Anaesth. 2016. Cricoid pressure used by ~92% of respondents.
20. Klucka J, Kosinova M, Zacharowski K, et al. Rapid sequence induction: an international survey. Eur J Anaesthesiol. 2020. Cricoid pressure used by ~38.5%.

Does ondansetron prevent spinal hypotension?

Published at /answers/ondansetron-spinal-hypotension.

1. Tubog TD, Kane TD, Pugh MA. Effects of ondansetron on attenuating spinal anesthesia–induced hypotension and bradycardia in obstetric and nonobstetric subjects: a systematic review and meta-analysis. AANA J. 2017;85(2):113–122. PMID 30501160. Thirteen RCTs, 1,225 subjects; doses 2–8 mg.
2. Zhou C, Zhu Y, Bao Z, Wang X, Liu Q. Efficacy of ondansetron for spinal anesthesia during cesarean section: a meta-analysis of randomized trials. J Int Med Res. 2018;46(2):654–662. doi:10.1177/0300060517716502. PMID 28856920. Twenty-one RCTs; hypotension RR 0.72 (0.50–1.06), not significant; pruritus RR 0.92 (0.83–1.02); shivering RR 0.89 (0.71–1.11); bradycardia RR 0.45 (0.26–0.80); nausea and vomiting RR 0.43 (0.36–0.51).
3. Hou XM, Chen YJ, Lai L, Liu K, Shen QH. Ondansetron reduces the incidence of hypotension after spinal anaesthesia: a systematic review and meta-analysis. Pharmaceuticals (Basel). 2022;15(12):1588. doi:10.3390/ph15121588. PMID 36559039. Twenty-five RCTs; hypotension RR 0.65 (0.53–0.80), I² = 64%; vasopressor requirement RR 0.50 (0.38–0.67), I² = 38%; bradycardia RR 0.56 (0.38–0.83), I² = 8%; ephedrine dose MD −2.81 mg (−4.72 to −0.89). Overall certainty rated moderate with high heterogeneity; the GRADE table rates bradycardia and vasopressor rescue HIGH within the analysis and hypotension and ephedrine dose MODERATE, each downgraded for serious inconsistency.
4. Gao L, Zheng G, Han J, Wang Y, Zheng J. Effects of prophylactic ondansetron on spinal anesthesia-induced hypotension: a meta-analysis. Int J Obstet Anesth. 2015;24(4):335–343. PMID 26421701.
5. Tubog TD, Bramble RS. Ondansetron reduces the incidence of hypotension after spinal anaesthesia in non-caesarean delivery: a systematic review and meta-analysis. J Perioper Pract. 2022. doi:10.1177/1750458920964157. Thirteen trials, 1,166 patients.
6. Mendonça FT, Crepaldi Junior LC, Gersanti RC, de Araújo KC. Effect of ondansetron on spinal anesthesia-induced hypotension in non-obstetric surgeries: a randomised, double-blind and placebo-controlled trial. Braz J Anesthesiol. 2021;71(3):233–240. doi:10.1016/j.bjane.2020.12.028. PMID 33766681. 144 patients, 8 mg.
7. Campagna JA, Carter C. Clinical relevance of the Bezold–Jarisch reflex. Anesthesiology. 2003;98(5):1250–1260. doi:10.1097/00000542-200305000-00030. PMID 12717149.
8. US Food and Drug Administration drug safety communication, 2012: the 32 mg single intravenous dose of ondansetron is removed from the market because of the risk of dose-dependent QT interval prolongation; the maximum single intravenous dose is capped at 16 mg. Dated 4 December 2012; the FDA page has since been withdrawn, and FDA directs readers to the archived copy: web.archive.org copy of fda.gov.
9. Samarah WK, Alghanem SM, Bsisu IK, Rahman ZA, Guzu HA, Abufares BN. The effect of ondansetron administration 20 minutes prior to spinal anaesthesia on haemodynamic status in patients undergoing elective caesarean section: a comparison between two different doses. Indian J Anaesth. 2020;64(11):954–959. doi:10.4103/ija.IJA_974_19. PMID 33487680. Ondansetron 4 mg or 6 mg against saline in elective cesarean delivery; no reduction in hypotension, with lower ephedrine consumption in both ondansetron groups.
10. Terkawi AS, Mavridis D, Flood P, et al. Does ondansetron modify sympathectomy due to subarachnoid anesthesia?: meta-analysis, meta-regression, and trial sequential analysis. Anesthesiology. 2016;124(4):846–869. Fourteen RCTs, 1,045 subjects. Conventional hypotension RR 0.62 (0.46–0.83) and bradycardia RR 0.44 (0.26–0.73); trial-sequential-analysis-adjusted intervals 0.34–1.12 and 0.05–3.85, respectively — neither confirmed. Body of evidence rated low to very-low quality.
11. Terkawi AS, Tiouririne M, Mehta SH, et al. Ondansetron does not attenuate hemodynamic changes in patients undergoing elective cesarean delivery using subarachnoid anesthesia: a double-blind, placebo-controlled, randomized trial. Reg Anesth Pain Med. 2015;40(4):344–348. Eighty-six patients, 8 mg; no attenuation of hemodynamic changes or vasopressor use.
12. Chooi C, Cox JJ, Lumb RS, et al. Techniques for preventing hypotension during spinal anaesthesia for caesarean section. Cochrane Database Syst Rev. 2020;(7):CD002251. Ondansetron RR 0.67 (0.54–0.83), low-quality; significant dose-subgroup difference with the 4 mg subgroup carrying the strongest effect (RR 0.46), and removal of the 4 mg subgroup abolished the overall benefit.
13. Heesen M, Klimek M, Hoeks SE, Rossaint R. Prevention of spinal anesthesia-induced hypotension during cesarean delivery by 5-hydroxytryptamine-3 receptor antagonists: a systematic review, meta-analysis and meta-regression. Anesth Analg. 2016;123(4):977–988. Seventeen trials, 1,604 patients; effect significant in the obstetric subgroup but not in non-obstetric patients (RR 0.50, 0.22–1.16); funnel-plot asymmetry consistent with publication bias; significant dose-response by meta-regression in non-obstetric patients.
14. Owczuk R, Wenski W, Twardowski P, et al. Ondansetron attenuates the decrease in blood pressure due to spinal anesthesia in the elderly: a double-blind, placebo-controlled study. Minerva Anestesiol. 2015;81(6):598–607. Fifty-three elderly patients, 8 mg vs placebo; attenuated the fall in diastolic and mean arterial pressure but not systolic pressure or heart rate.
15. Xiao F, Wei C, Chang X, et al. A prospective, randomized, double-blinded study of the effect of intravenous ondansetron on the ED50 of prophylactic phenylephrine infusions for preventing spinal anesthesia-induced hypotension during cesarean delivery. Anesth Analg. 2020;131(2):564–569. 4 mg ondansetron reduced the phenylephrine infusion ED50 by roughly 26%.
16. Sheng ZM, Sun HQ, Mao JQ, et al. Comparative dose-response study on the infusion of norepinephrine combined with intravenous ondansetron versus placebo for preventing hypotension during spinal anesthesia for cesarean section: a randomised controlled trial. Int J Surg. 2024. Ondansetron lowered the norepinephrine infusion ED50 and ED90.
17. Lee S, Islam N, Ladha KS, Bicket MC, Wijeysundera DN. Prevention of hypotension after neuraxial anesthesia in nonobstetric surgery: a systematic review. Can J Anaesth. 2025. Prophylactic ondansetron RR 0.64 (0.53–0.78), moderate certainty.
18. Xiao F, Xu Q, Yang ZS, et al. The effect of intravenous ondansetron on maternal spinal-induced hypotension in preeclamptic patients undergoing caesarean delivery: a randomised, controlled clinical trial. Eur J Anaesthesiol. 2026. 4 mg ondansetron; hypotension RR 0.55 (0.34–0.84).
19. Neumann C, Velten M, Heik-Guth C, et al. 5-HT3 blockade does not attenuate postspinal blood pressure change in cesarean section: a case-control study. Medicine (Baltimore). 2020;99(30):e21393. 8 mg; no attenuation of postspinal blood pressure change and higher vasopressor use in the ondansetron group.
20. Lovelace JW, Ma J, Yadav S, et al. Vagal sensory neurons mediate the Bezold–Jarisch reflex and induce syncope. Nature. 2023;623(7986):387–396. Localizes the afferent limb of the reflex to a defined population of ventricular vagal sensory neurons.
21. Kim MK, Kim I, Kang H, et al. Effect of intravenous palonosetron on hypotension induced by spinal anesthesia for cesarean section: a randomized controlled trial. PLoS One. 2023;18(5):e0285120. No difference from ondansetron in phenylephrine requirement.
22. US Food and Drug Administration. Ondansetron prescribing information. ECG monitoring recommended in patients with electrolyte abnormalities (hypokalemia, hypomagnesemia), congestive heart failure, bradyarrhythmias, congenital long QT syndrome, or concurrent QT-prolonging drugs.
23. Yang F, Xu L, Lang X, Feng X. A real-world safety signal detection study of ondansetron based on FAERS reports from 2014 to 2024. Sci Rep. 2025. QT prolongation among prominent disproportionality signals.
24. Al-Ramadan A, Kidess GG, Bahar AR, et al. Morbidity and mortality of ondansetron in patients with non-congenital long QT syndrome: a review article. Cardiovasc Drugs Ther. 2026.

Does one dose of etomidate have long-term consequences?

Published at /answers/etomidate-single-dose-long-term-outcomes.

1. Komatsu R, You J, Mascha EJ, Sessler DI, Kasuya Y, Turan A. Anesthetic induction with etomidate, rather than propofol, is associated with increased 30-day mortality and cardiovascular morbidity after noncardiac surgery. Anesth Analg. 2013;117(6):1329–1337. PMID 24257383.
2. Use of etomidate in patients with heart failure undergoing noncardiac surgery. Br J Anaesth. 2020;125(6):943–952. PMID 32807381. Retrospective cohort of 19,714 heart failure patients across two tertiary institutions, 2006–2017; instrumental-variable analysis using anesthesiologist preference for etomidate. Source of the reported 6.5% vs 2.5% 30-day mortality figures from the Komatsu cohort and of the critique of its propensity model.
3. Lu Z, Zheng H, Chen Z, et al. Effect of etomidate vs propofol for total intravenous anesthesia on major postoperative complications in older patients: a randomized clinical trial (EPIC). JAMA Surg. 2022;157(10):888–895. PMID 35947398.
4. Casey JD, Seitz KP, Driver BE, et al. Ketamine or etomidate for tracheal intubation of critically ill adults. N Engl J Med. 2026;394(16):1608–1620. doi:10.1056/NEJMoa2511420. Epub 2025 Dec 9. PMID 41369227. The RSI trial; 2,365 patients randomized across 14 US emergency departments and ICUs, 2,359 with the primary outcome assessed.
5. Zampieri FG, Schmidt RC, Besen BAMP, et al. Induction agents for emergency tracheal intubation in critically ill adults: a systematic review and network meta-analysis. Crit Care. 2026;30:296. doi:10.1186/s13054-026-06067-w.
6. Comparison of efficacy and safety of etomidate with other anesthesia induction drugs for patients undergoing cardiac surgery: a systematic review and meta-analysis of randomized controlled trials. Heliyon. 2024;10(22):e38274. doi:10.1016/j.heliyon.2024.e38274. PMID 39584115. Sixteen randomized trials, 1,162 patients; 30-day all-cause mortality RR 0.96 (95% CI 0.26–3.49).
7. Wagner CE, Bick JS, Johnson D, et al. Etomidate use and postoperative outcomes among cardiac surgery patients. Anesthesiology. 2014;120(3):579–589. PMID 24296761.
8. Kotani Y, Piersanti G, Maiucci G, et al. Etomidate as an induction agent for endotracheal intubation in critically ill patients: a meta-analysis of randomized trials. J Crit Care. 2023;77:154317. PMID 37127020.
9. Duration of adrenal inhibition following a single dose of etomidate in critically ill patients. Intensive Care Med. 2008. PMID 18092151. Forty patients; serial cortisol and 11β-deoxycortisol after 250 µg corticotropin stimulation at 12, 24, 48 and 72 hours.
10. Etomidate. StatPearls. NCBI Bookshelf NBK535364. Describes dose-dependent 11β-hydroxylase inhibition lasting 6 to 12 hours after a single bolus.
11. Hildreth AN, Mejia VA, Maxwell RA, Smith PW, Dart BW, Barker DE. Adrenal suppression following a single dose of etomidate for rapid sequence induction: a prospective randomized study. J Trauma. 2008;65(3):573–579. PMID 18784570.
12. Komatsu R, You J, Rajan S, Kasuya Y, Sessler DI, Turan A. Steroid administration after anaesthetic induction with etomidate does not reduce in-hospital mortality or cardiovascular morbidity after non-cardiac surgery. Br J Anaesth. 2018;120(3):501–508. PMID 29452806.
13. Infectious complications after etomidate vs propofol for induction of general anesthesia in cardiac surgery: results of a retrospective, before–after study. J Clin Med. 2021;10(13):2908. doi:10.3390/jcm10132908.
14. Etomidate increases susceptibility to pneumonia in trauma patients. Intensive Care Med. 2012. doi:10.1007/s00134-012-2619-8.
15. Jabre P, Combes X, Lapostolle F, et al; KETASED Collaborative Study Group. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009;374(9686):293–300. doi:10.1016/S0140-6736(09)60949-1. PMID 19573904.
16. Matchett G, Gasanova I, Riccio CA, et al. Etomidate versus ketamine for emergency endotracheal intubation: a randomized clinical trial. Intensive Care Med. 2022;48(1):78–91. PMID 34904190.
17. Maia IWA, Decker SRR, Oliveira e Silva L, et al; Brazilian Airway Registry Cooperation (BARCO) group. Ketamine, etomidate, and mortality in emergency department intubations. JAMA Netw Open. 2025;8(12):e2548060. doi:10.1001/jamanetworkopen.2025.48060. PMID 41396604. PMC12706683. Observational registry reporting higher 28-day mortality with etomidate (60.5% vs 54.4%), discordant with the randomized evidence.

Drug-eluting stents: how long before surgery?

Published at /answers/elective-surgery-timing-after-drug-eluting-stent.

1. Thompson A, Fleischmann KE, Smilowitz NR, et al. 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery. Circulation. 2024;150(19):e351–e442. doi:10.1161/CIR.0000000000001285. Also published as J Am Coll Cardiol. 2024;84(19):1869–1969. PMID 39320289. Supersedes the 2014 guideline. Source of every interval and class in the table above, the 30-day harm statement, the aspirin and dual therapy recommendations, the multidisciplinary recommendation, and the position on bridging.
2. Cohn SL. 2024 ACC/AHA guideline on perioperative cardiovascular management before noncardiac surgery: what’s new? Cleve Clin J Med. 2025;92(4):213–219. doi:10.3949/ccjm.92a.24125. Source of the revised urgency definitions, the complex-anatomy 12-month note, the antiplatelet hold intervals, and the European high-risk feature list as summarized there.
3. Wijeysundera DN, Wijeysundera HC, Yun L, Wąsowicz M, Beattie WS, Velianou JL, Ko DT. Risk of elective major noncardiac surgery after coronary stent insertion: a population-based study. Circulation. 2012;126(11):1355–1362. doi:10.1161/CIRCULATIONAHA.112.102715. PMID 22893606. 8,116 stented patients versus 341,350 nonrevascularized; overall 30-day events 2.1%; under 45 days 20.0% drug-eluting and 6.7% bare-metal; 45–180 days bare-metal 2.6%; beyond 180 days drug-eluting 1.2%.
4. Hawn MT, Graham LA, Richman JS, Itani KMF, Henderson WG, Maddox TM. Risk of major adverse cardiac events following noncardiac surgery in patients with coronary stents. JAMA. 2013;310(14):1462–1472. doi:10.1001/jama.2013.278787. PMID 24101118. 28,029 operations, 1,980 events (4.7%). Nonelective admission adjusted OR 4.77 (4.07–5.59); myocardial infarction in the preceding 6 months 2.63 (2.32–2.98); Revised Cardiac Risk Index above 2 2.13 (1.85–2.44). Drug-eluting stent 0.91 (0.83–1.01), not significant. Case-control of 284 matched pairs, antiplatelet cessation OR 0.86 (0.57–1.29).
5. Holcomb CN, Graham LA, Richman JS, Rhyne RR, Itani KMF, Maddox TM, Hawn MT. The incremental risk of noncardiac surgery on adverse cardiac events following coronary stenting. J Am Coll Cardiol. 2014;64(25):2730–2739. doi:10.1016/j.jacc.2014.09.072. PMID 25541124. 20,590 surgical patients matched to 41,180 nonsurgical; composite 3.1% versus 1.9%, risk difference 1.3% (1.0–1.5); incremental risk 3.5% immediately after stenting, 1% at 6 months, stable to 24 months.
6. Egholm G, Kristensen SD, Thim T, et al. Risk associated with surgery within 12 months after coronary drug-eluting stent implantation. J Am Coll Cardiol. 2016;68(24):2622–2632. doi:10.1016/j.jacc.2016.09.967. PMID 27978946. 4,303 stented surgical patients versus 20,232 without ischemic heart disease. Myocardial infarction 1.6% versus 0.2% (OR 4.82, 3.25–7.16); cardiac death 1.0% versus 0.2% (OR 5.87, 3.60–9.58); all-cause mortality 3.1% versus 2.7% (OR 1.12, 0.91–1.38, not significant). Only the first month significant on stratification.
7. Egholm G, Thim T, Olesen KKW, Madsen M, Jensen SE, Jensen LO, Bøtker HE, Kristensen SD, Maeng M. Risk of adverse cardiac events in patients undergoing surgery after coronary drug-eluting stent implantation for acute coronary syndrome and stable angina pectoris. Eur Heart J. 2017;38(Suppl 1):ehx502.P2330. doi:10.1093/eurheartj/ehx502.P2330. Congress abstract. The same cohort was later published in full as reference 15, though with a general-population comparator rather than a head-to-head comparison, so the odds ratio below has no published counterpart. Postoperative myocardial infarction 1.9% versus 0.6%, OR 3.21 (1.76–5.83), adjusted 2.50 (1.35–4.61); first month 8.6% versus 2.7%, OR 2.80 (1.26–6.20); months 1–12 0.6% versus 0.3%, OR 2.05 (0.77–5.50), not significant; all-cause mortality adjusted OR 0.90 (0.64–1.26). This is the origin of the “threefold” figure quoted elsewhere for the acute coronary syndrome indication.
8. Butala NM, et al. Outcomes after noncardiac surgery performed within 2 years of percutaneous coronary intervention. J Am Heart Assoc. 2025;14(6):e038807. doi:10.1161/JAHA.124.038807. PMID 40079295. 334,828 operations 2017–2021; 2,297 (0.68%) with intervention within 2 years. Among 9,160 propensity-matched patients, no difference in 1-year major adverse cardiovascular events (HR 1.04, 0.96–1.17); lower all-cause death (0.83, 0.72–0.96); higher revascularization (1.88, 1.50–2.36).
9. Devereaux PJ, Mrkobrada M, Sessler DI, et al; POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014;370(16):1494–1503. doi:10.1056/NEJMoa1401105. PMID 24679062. 10,010 patients; death or nonfatal myocardial infarction 7.0% versus 7.1%, hazard ratio 0.99 (0.86–1.15); major bleeding 4.6% versus 3.8%, hazard ratio 1.23 (1.01–1.49).
10. Graham MM, Sessler DI, Parlow JL, et al. Aspirin in patients with previous percutaneous coronary intervention undergoing noncardiac surgery. Ann Intern Med. 2018;168(4):237–244. doi:10.7326/M17-2341. PMID 29132159. Non-prespecified subgroup of 470 within POISE-2. Death or nonfatal myocardial infarction absolute risk reduction 5.5% (0.4–10.5), hazard ratio 0.50 (0.26–0.95); myocardial infarction 5.9% (1.0–10.8), 0.44 (0.22–0.87). Also the source for POISE-2’s exclusion of bare-metal stents within 6 weeks and drug-eluting stents within 1 year.
11. Angiolillo DJ, Firstenberg MS, Price MJ, et al; BRIDGE Investigators. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA. 2012;307(3):265–274. doi:10.1001/jama.2011.2002. PMID 22253393. 210 patients awaiting coronary artery bypass grafting. Primary endpoint was platelet reactivity: below 240 reaction units in 98.8% versus 19.0%, relative risk 5.2 (3.3–8.1). Cardiac surgery and a surrogate endpoint, both of which limit what it can be cited for.
12. Kałuża GL, Joseph J, Lee JR, Raizner ME, Raizner AE. Catastrophic outcomes of noncardiac surgery soon after coronary stenting. J Am Coll Cardiol. 2000;35(5):1288–1294. doi:10.1016/s0735-1097(00)00521-0. PMID 10758971. 40 consecutive patients operated within six weeks of stenting: 7 myocardial infarctions, 11 major bleeding episodes, 8 deaths; all deaths and infarctions in patients operated fewer than 14 days from stenting.
13. Halvorsen S, Mehilli J, Cassese S, et al. 2022 ESC guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery. Eur Heart J. 2022;43(39):3826–3924. doi:10.1093/eurheartj/ehac270. PMID 36017553. Six months after elective intervention and twelve after acute coronary syndrome, both Class I; a minimum of one month of completed dual antiplatelet therapy before time-sensitive surgery after elective intervention, Class I; P2Y12 stop intervals of ticagrelor 3–5 days, clopidogrel 5 days, prasugrel 7 days; the high-thrombotic-risk feature list; the preference for current-generation drug-eluting stents when intervention is indicated before surgery; and restarting interrupted antiplatelet therapy as soon as possible, within 48 hours after surgery, Class I.
14. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease. Circulation. 2016;134(10):e123–e155. doi:10.1161/CIR.0000000000000404. PMID 27026020. The document that moved the drug-eluting stent interval from 12 months to 6, and the source of the rule that aspirin is continued and the P2Y12 inhibitor restarted as soon as possible after surgery.
15. Thim T, Egholm G, Kristensen SD, Olesen KKW, Madsen M, Jensen SE, Jensen LO, Sørensen HT, Bøtker HE, Maeng M. Risk of myocardial infarction and death after noncardiac surgery performed within the first year after coronary drug-eluting stent implantation for acute coronary syndrome or stable angina pectoris. Am J Cardiol. 2021;160:14–20. doi:10.1016/j.amjcard.2021.08.040. PMID 34583812. Full publication of the cohort behind reference 7: 2,291 acute coronary syndrome and 1,804 stable angina patients, each compared with a matched general-population cohort without known coronary artery disease rather than with each other.

GLP-1 agonists and anesthesia: hold or continue?

Published at /answers/glp1-agonists-anesthesia.

1. Joshi GP, Abdelmalak BB, Weigel WA, et al. American Society of Anesthesiologists consensus-based guidance on preoperative management of patients (adults and children) on glucagon-like peptide-1 (GLP-1) receptor agonists. ASA, June 2023. asahq.org/about-asa/newsroom/news-releases/2023/06/american-society-of-anesthesiologists-consensus-based-guidance-on-preoperative. Includes the Klein & Hobai case report of semaglutide, delayed gastric emptying and intraoperative pulmonary aspiration.
2. Multisociety clinical practice guidance for the safe use of glucagon-like peptide-1 receptor agonists in the perioperative period. Clin Gastroenterol Hepatol. doi:10.1016/j.cgh.2024.10.003. PMID 39480373. Also published in Surg Obes Relat Dis. 2024;20(12):1183–1186.
3. New multi-society GLP-1 clinical practice guidance released. American Society of Anesthesiologists news release, 29 October 2024. asahq.org/about-asa/newsroom/news-releases/2024/10/new-multi-society-glp-1-guidance. Continuation for most patients; 24-hour liquid diet for highest-risk; deferral both for GI symptoms and through dose escalation; the overweight and obesity bias statement; approximately one in eight US adults using GLP-1 drugs.
4. Jones T. How should GLP-1 receptor agonists be managed in the perioperative period? Anesthesia Thoughts, 27 January 2026. anesthesiathoughts.com/p/how-should-glp-1-receptor-agonists. Commentary noting that five half-lives — about five weeks for weekly semaglutide — would be required to normalize gastric emptying, and that emptying often normalizes on a stable dose.
5. Idris I, et al. Multi-society consensus guidance on handling of GLP-1 therapy prior to general anaesthesia. Diabetes Obes Metab Now. 2024. doi:10.1002/doi2.70009. Summarizes the risk factors: escalation phase, higher dose, weekly versus daily formulation.
6. Silveira SQ, da Silva LM, de Campos Vieira Abib A, et al. Relationship between perioperative semaglutide use and residual gastric content: a retrospective analysis of patients undergoing elective upper endoscopy. J Clin Anesth. 2023;87:111091. doi:10.1016/j.jclinane.2023.111091. PMID 36870274.
7. Sherwin M, Hamburger J, Katz D, et al. Influence of semaglutide use on the presence of residual gastric solids on gastric ultrasound: a prospective observational study in volunteers without obesity recently started on semaglutide. Can J Anaesth. 2023;70(8):1300–1306. doi:10.1007/s12630-023-02549-5. PMID 37466909.
8. Sen S, Potnuru PP, Hernandez N, et al. Glucagon-like peptide-1 receptor agonist use and residual gastric content before anesthesia. JAMA Surg. 2024;159(6):660–667. doi:10.1001/jamasurg.2024.0111. PMID 38446466. PMC10918573.
9. Hiramoto B, McCarty T, Lodhia N, et al. Quantified metrics of gastric emptying delay by glucagon-like peptide-1 agonists: a systematic review and meta-analysis with insights for periprocedural management. Am J Gastroenterol. 2024;119(6):1126–1140. doi:10.14309/ajg.0000000000002820. PMID 38634551. PMC11150091.
10. Hosmer AE. Perioperative management of GLP-1 receptor agonists. ASGE Journal Scan, General Endoscopy, reviewing Kindel TL, et al. Clin Gastroenterol Hepatol. 2025. asge.org/home/resources/publications/journal-scan/issue/perioperative-management-of-glp-1-receptor-agonists. A journal summary of the multisociety guidance at reference 2, not a statement of ASGE’s own position, which is at reference 20 and differs from it.
11. Oprea AD, Ostapenko LJ, Sweitzer B, et al. Perioperative management of patients taking glucagon-like peptide 1 receptor agonists: Society for Perioperative Assessment and Quality Improvement (SPAQI) multidisciplinary consensus statement. Br J Anaesth. 2025;135(1):48–78. doi:10.1016/j.bja.2025.04.001. PMID 40379536. Modified Delphi with a registered systematic review (PROSPERO CRD42023438624); source of the recommendation grades, the symptom definition, and the pharmacokinetic table.
12. El-Boghdadly K, Dhesi J, Fabb P, et al. Elective peri-operative management of adults taking glucagon-like peptide-1 receptor agonists, glucose-dependent insulinotropic peptide agonists and sodium-glucose cotransporter-2 inhibitors: a multidisciplinary consensus statement. Anaesthesia. 2025;80(4):412–424. doi:10.1111/anae.16541. PMID 39781571. PMC11885194.
13. Boudreau B, Watson NC. Anesthesiologists’ perspectives on GLP-1 receptor agonists in elective surgeries: a qualitative survey analysis of national data. Cureus. 2025;17(11):e95986. doi:10.7759/cureus.95986
14. Chang MG, Bittner EA. Comparison of societal guidance on perioperative management of glucagon-like peptide-1 receptor agonists: implications for clinical practice and future investigations. Can J Anaesth. 2024;71(9):1302–1315. doi:10.1007/s12630-024-02810-5. PMID 39187641
15. American Diabetes Association. Introduction: Standards of Medical Care in Diabetes—2022. Diabetes Care. 2022;45(Suppl 1):S1–S2. doi:10.2337/dc22-Sint. PMID 34964812. The document cited by SPAQI (reference 11) for its grading. Source of the evidence grading scheme SPAQI applies: A, clear evidence from well-conducted, generalizable, adequately powered randomized controlled trials; B, supportive evidence from well-conducted cohort studies; C, supportive evidence from poorly controlled or uncontrolled studies; E, expert consensus or clinical experience.
16. Khandaker R, Jahantighi AB, Schwarz J, et al. Perioperative management of patients taking glucagon-like peptide-1 receptor agonists: a restrictive fasting regimen is not necessary. Br J Anaesth. 2025;135(6):1816–1818. doi:10.1016/j.bja.2025.09.027. PMID 41125490.
17. Frank C, El-Boghdadly K, Dhesi J. Perioperative management of patients taking glucagon-like peptide-1 receptor agonists: implementation of complex fasting recommendations. Br J Anaesth. 2026;136(1):375–376. doi:10.1016/j.bja.2025.09.028. PMID 41162252.
18. Semaglutide tablets (Rybelsus, Ozempic) prescribing information. Novo Nordisk. DailyMed structured product label, revised January 2026. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=27f15fac-7d98-4114-a2ec-92494a91da98. Source of the administration requirements — empty stomach, up to 4 ounces of water, water only, and at least 30 minutes before food, other beverages or other oral medications — and of the statement that the two oral products are not substitutable on a milligram-for-milligram basis.
19. Choi UE, Nicholson RC, Messinger C, et al. Preoperative glucagon-like peptide-1 receptor agonists and postoperative outcomes: an observational analysis. Anesthesiology. Published online 12 August 2026. doi:10.1097/ALN.0000000000006326. PMID 42585629. Propensity-matched analysis of adults with type 2 diabetes in the TriNetX Research Network, using data predating the 2023 hold guidance.
20. Sharaiha RZ, Shukla AP, Sen S, et al. American Society for Gastrointestinal Endoscopy position statement on periendoscopic management of patients on glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Gastrointest Endosc. 2025;101(2):285–294. doi:10.1016/j.gie.2024.10.057. PMID 39892967. Read in full. Statement 3 suggests a 24-hour liquid diet before endoscopy for all patients on GLP-1 receptor agonists. Statement 9 suggests holding before elective endoscopy: at least 24 hours for daily dosing, at least seven days for weekly, with 100% panel agreement. Statements 4 and 6 recommend against delaying urgent, emergent or time-sensitive endoscopy. The statement makes no recommendation on gastric ultrasound.

Intraoperative hypotension: differential, management, and MAP targets

Published at /answers/intraoperative-hypotension-map-targets.

1. Thompson A, Fleischmann KE, Smilowitz NR, et al. 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM guideline for perioperative cardiovascular management for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2024;84(19):1869–1969. doi:10.1016/j.jacc.2024.06.013. PMID 39320289.
2. Ruetzler K, Smilowitz NR, Berger JS, et al. Diagnosis and management of patients with myocardial injury after noncardiac surgery: a scientific statement from the American Heart Association. Circulation. 2021;144(19):e287–e305. doi:10.1161/CIR.0000000000001024. PMID 34601955.
3. Saugel B, Meidert AS, Brunkhorst FM, et al. Individualized perioperative blood pressure management in patients undergoing major abdominal surgery: the IMPROVE-multi randomized clinical trial. JAMA. 2025;334(21):1893–1904. doi:10.1001/jama.2025.17235. PMID 41076588.
4. Legrand M, Lamontagne F, Pirracchio R. Perioperative outcomes — the limits of blood pressure–centered strategies. JAMA. 2025;334(21):1885–1887. doi:10.1001/jama.2025.18572. PMID 41076589.
5. Irani JL, Hedrick TL, Miller TE, et al. Clinical practice guidelines for enhanced recovery after colon and rectal surgery from the American Society of Colon and Rectal Surgeons and the Society of American Gastrointestinal and Endoscopic Surgeons. Surg Endosc. 2023;37(1):5–30. doi:10.1007/s00464-022-09758-x. PMID 36515747.
6. Sun Z, Wang K, Ji P. Incidence and risk factors for perioperative hypotension during noncardiac surgery: a retrospective cohort study. Medicine (Baltimore). 2026;105(2):e46451. doi:10.1097/MD.0000000000046451. PMID 41517769.
7. Benesch C, Glance LG, Derdeyn CP, et al. Perioperative neurological evaluation and management to lower the risk of acute stroke in patients undergoing noncardiac, nonneurological surgery: a scientific statement from the American Heart Association/American Stroke Association. Circulation. 2021;143(19):e923–e946. doi:10.1161/CIR.0000000000000968. PMID 33827230.
8. Sessler DI, Bloomstone JA, Aronson S, et al. Perioperative Quality Initiative consensus statement on intraoperative blood pressure, risk and outcomes for elective surgery. Br J Anaesth. 2019;122(5):563–574. doi:10.1016/j.bja.2019.01.013. PMID 30916004.
9. Wesselink EM, Kappen TH, Torn HM, Slooter AJC, van Klei WA. Intraoperative hypotension and the risk of postoperative adverse outcomes: a systematic review. Br J Anaesth. 2018;121(4):706–721. doi:10.1016/j.bja.2018.04.036. PMID 30236233.
10. Tran PNT, Kusirisin P, Kaewdoungtien P, Phannajit J, Srisawat N. Higher blood pressure versus normotension targets to prevent acute kidney injury: a systematic review and meta-regression of randomized controlled trials. Crit Care. 2022;26(1):364. doi:10.1186/s13054-022-04236-1. PMID 36434726.
11. American Society of Anesthesiologists, Committee on Obstetric Anesthesia. Statement on Quality Metrics. Approved October 26, 2022. asahq.org/standards-and-practice-parameters/statement-on-quality-metrics.
12. Wildey B, Berman D, Borahay MA. Cardiovascular collapse during laparoscopy: a brief overview. Arch Gynecol Obstet. 2024;309(5):2253–2256. doi:10.1007/s00404-023-07274-4. PMID 38015208.
13. Manian DV, Volcheck GW. Perioperative anaphylaxis: evaluation and management. Clin Rev Allergy Immunol. 2022;62(3):383–399. doi:10.1007/s12016-021-08874-1. PMID 34247332.
14. Rajagopal S, Ruetzler K, Ghadimi K, et al. Evaluation and management of pulmonary hypertension in noncardiac surgery: a scientific statement from the American Heart Association. Circulation. 2023;147(17):1317–1343. doi:10.1161/CIR.0000000000001136. PMID 36924225.
15. van Klei WA, Szabo MD, Hesterberg PE. Case 22-2023: a 59-year-old woman with hypotension and electrocardiographic changes. N Engl J Med. 2023;389(3):263–272. doi:10.1056/NEJMcpc2300898. PMID 37467501.
16. Pouessel G, Dribin TE, Tacquard C, et al. Management of refractory anaphylaxis: an overview of current guidelines. Clin Exp Allergy. 2024;54(7):470–488. doi:10.1111/cea.14514. PMID 38866583.
17. Pflipsen MC, Vega Colon KM. Anaphylaxis: recognition and management. Am Fam Physician. 2020;102(6):355–362. PMID 32931210.
18. Kawasaki S, Kiyohara C, Tokunaga S, Hoka S. Prediction of hemodynamic fluctuations after induction of general anesthesia using propofol in non-cardiac surgery: a retrospective cohort study. BMC Anesthesiol. 2018;18(1):167. doi:10.1186/s12871-018-0633-2. PMID 30414607.
19. Li X, Zheng Y, Zhang J. Cerebral oxygenation and hemodynamic changes during ephedrine and phenylephrine administration for transient intraoperative hypotension in patients undergoing major abdominal surgery: a randomized controlled trial. BMC Anesthesiol. 2025;25(1):87. doi:10.1186/s12871-025-02944-z. PMID 39979813.
20. Fresenius Kabi USA, LLC. Phenylephrine hydrochloride injection, 10 mg/mL — prescribing information. Revised July 2025. DailyMed setid b54a0c59-e5e4-4fd7-ba91-c991ce87b148. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b54a0c59-e5e4-4fd7-ba91-c991ce87b148.
21. Kotani Y, Belletti A, D'Amico F, et al. Non-adrenergic vasopressors for vasodilatory shock or perioperative vasoplegia: a meta-analysis of randomized controlled trials. Crit Care. 2024;28(1):439. doi:10.1186/s13054-024-05212-7. PMID 39736782.
22. Busse LW, Barker N, Petersen C. Vasoplegic syndrome following cardiothoracic surgery — review of pathophysiology and update of treatment options. Crit Care. 2020;24(1):36. doi:10.1186/s13054-020-2743-8. PMID 32019600.
23. Hospira, Inc. Dobutamine in 5% dextrose injection — prescribing information. Revised November 2025. DailyMed setid 9943a961-3b50-4847-8a84-d8414ce38daa. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9943a961-3b50-4847-8a84-d8414ce38daa.
24. Konstam MA, Kiernan MS, Bernstein D, et al. Evaluation and management of right-sided heart failure: a scientific statement from the American Heart Association. Circulation. 2018;137(20):e578–e622. doi:10.1161/CIR.0000000000000560. PMID 29650544.
25. Hikma Pharmaceuticals USA Inc. Milrinone lactate injection, USP — prescribing information. Revised May 2025. DailyMed setid 88f78780-399f-4780-be19-205739db1682. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=88f78780-399f-4780-be19-205739db1682.
26. Naylor AJ, Sessler DI, Maheshwari K, et al. Arterial catheters for early detection and treatment of hypotension during major noncardiac surgery: a randomized trial. Anesth Analg. 2020;131(5):1540–1550. doi:10.1213/ANE.0000000000004370. PMID 33079877.
27. Kouz K, Wegge M, Flick M, et al. Continuous intra-arterial versus intermittent oscillometric arterial pressure monitoring and hypotension during induction of anaesthesia: the AWAKE randomised trial. Br J Anaesth. 2022;129(4):478–486. doi:10.1016/j.bja.2022.06.027. PMID 36008202.
28. Par Health USA, LLC. Vasostrict (vasopressin injection) — prescribing information. Revised February 2023. DailyMed setid b1147beb-743e-4c62-8927-91192447f8b8. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b1147beb-743e-4c62-8927-91192447f8b8.
29. Belkin MN, Fudim M, Baratto C, et al. Standardization of baseline and provocative invasive hemodynamic protocols for the evaluation of heart failure and pulmonary hypertension: a scientific statement from the American Heart Association. Circ Heart Fail. 2026;19(2):e000088. doi:10.1161/HHF.0000000000000088. PMID 41493051.
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33. Exela Pharma Sciences, LLC. Nipride RTU (sodium nitroprusside) injection — prescribing information. Revised July 2018. DailyMed setid 5acf0836-93ff-4064-b888-3f560e8a558d. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5acf0836-93ff-4064-b888-3f560e8a558d.
34. Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023;148(16):e149–e184. doi:10.1161/CIR.0000000000001161. PMID 37721023.
35. Cao D, Arens AM, Chow SL, et al. Part 10: adult and pediatric special circumstances of resuscitation: 2025 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2025;152(16 suppl 2):S578–S672. doi:10.1161/CIR.0000000000001380. PMID 41122889.
36. BTG International Inc. Cyanokit (hydroxocobalamin for injection) — prescribing information. Revised May 2021. DailyMed setid d56fcc8d-bd64-46ab-b0c0-2124bd745a6b. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d56fcc8d-bd64-46ab-b0c0-2124bd745a6b.
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Intrathecal morphine: who follows the patient for 24 hours?

Published at /answers/intrathecal-morphine-24-hour-monitoring-responsibility.

1. DURAMORPH (morphine sulfate injection), for intravenous, epidural, or intrathecal use. FDA-approved labeling, Hikma Pharmaceuticals USA. DailyMed SPL set ID ebb18761-e5c4-4238-bb84-f9549f500210. Equivalent language appears in generic preservative-free morphine sulfate injection labeling and in the INFUMORPH label.
2. Practice Guidelines for the Prevention, Detection, and Management of Respiratory Depression Associated with Neuraxial Opioid Administration: An Updated Report by the American Society of Anesthesiologists Task Force on Neuraxial Opioids and the American Society of Regional Anesthesia and Pain Medicine. Anesthesiology. 2016;124(3):535–552. doi:10.1097/ALN.0000000000000975. PMID 26655725. Updates the 2009 report at Anesthesiology 110:218–30.
3. 42 CFR §482.52, Condition of participation: Anesthesia services. Current text via eCFR: ecfr.gov/current/title-42/chapter-IV/subchapter-G/part-482/subpart-D/section-482.52.
4. CMS State Operations Manual, Appendix A, anesthesia services interpretive guidelines (Transmittal R59SOMA, cms.gov/Regulations-and-Guidance/Guidance/Transmittals/downloads/R59SOMA.pdf); CMS Survey and Certification letter 11-10, January 2011, revised guidance on anesthesia versus analgesia and on pre- and post-anesthesia evaluations. cms.gov/Medicare/Provider-Enrollment-and-Certification/SurveyCertificationGenInfo/downloads/SCLetter11_10.pdf.
5. The Joint Commission. Sentinel Event Alert Issue 49: Safe use of opioids in hospitals. 8 August 2012. The alert cites requirement PC.01.02.07, EP 2 against its recommendation on standardized screening tools, not against its monitoring recommendation.
6. El-Boghdadly K, Renard Y, Rossel JB, Moka E, Volk T, Rawal N, Jaques C, Szyszko M, Albrecht E. Pulmonary complications after intrathecal morphine administration: a systematic review and meta-analysis with meta-regression and trial sequential analysis. Anaesthesia. 2025;80(8):959–972. doi:10.1111/anae.16606. PMID 40235368.
7. Meylan N, Elia N, Lysakowski C, Tramèr MR. Benefit and risk of intrathecal morphine without local anaesthetic in patients undergoing major surgery: meta-analysis of randomized trials. Br J Anaesth. 2009;102(2):156–167. doi:10.1093/bja/aen368.
8. Bai JW, Singh M, Short A, Bozak D, Chung F, Chan VWS, Bhatia A, Perlas A. Intrathecal morphine and pulmonary complications after arthroplasty in patients with obstructive sleep apnea: a retrospective cohort study. Anesthesiology. 2020;132(4):702–712. PMID 31977522.
9. Rawal N. Intrathecal opioids for the management of post-operative pain. Best Pract Res Clin Anaesthesiol. 2023;37(2):123–132. doi:10.1016/j.bpa.2023.01.001. PMID 37321761. Source of the low-dose ward-management position and the call for updated society guidance.
10. Grape S, El-Boghdadly K, Albrecht E. Management of adverse effects of intrathecal opioids in acute pain. Best Pract Res Clin Anaesthesiol. 2023;37(2):199–207. doi:10.1016/j.bpa.2023.02.002. PMID 37321767.
11. Oklahoma Attorney General Opinion 2024-14 (2024 OK AG 14), addressing the CRNA supervision opt-out, oklahoma.gov/oag/opinions/ag-opinions/2024/ag-opinion-24-14.html; 59 O.S. §567.3a(10)(b) and (h); Senate Bill 801, 2020 Okla. Sess. Laws ch. 11, §1, replacing physician supervision of CRNAs with a collaboration standard.
12. Renard Y, El-Boghdadly K, Rossel JB, Nguyen A, Jaques C, Albrecht E. Non-pulmonary complications of intrathecal morphine administration: a systematic review and meta-analysis with meta-regression. Br J Anaesth. 2024;133(4):823–838. doi:10.1016/j.bja.2024.05.045. PMID 39098521.
13. Gonvers E, El-Boghdadly K, Grape S, Albrecht E. Efficacy and safety of intrathecal morphine for analgesia after lower joint arthroplasty: a systematic review and meta-analysis with meta-regression and trial sequential analysis. Anaesthesia. 2021;76(12):1648–1658. doi:10.1111/anae.15569. PMID 34448492. PMC9292760.
14. Koning MV, Klimek M, Rijs K, Stolker RJ, Heesen MA. Intrathecal hydrophilic opioids for abdominal surgery: a meta-analysis, meta-regression, and trial sequential analysis. Br J Anaesth. 2020;125(3):358–372. doi:10.1016/j.bja.2020.05.061. Forty trials, 2,500 patients; excludes caesarean section and continuous neuraxial techniques.
15. Hussain N, Brull R, Thaete L, Fuller S, D’Souza RS, Mankinen-Abdallah Y, Essandoh MK, Weaver TE, Abdallah FW. The analgesic effects of novel fascial plane blocks compared with intrathecal morphine after Caesarean delivery: a systematic review and meta-analysis. Br J Anaesth. 2025;134(5):1415–1431. doi:10.1016/j.bja.2025.01.032.
16. Foadi N, Karst M, Frese-Gaul A, Rahe-Meyer N, Kromer S, Weilbach C. The improved quality of postoperative analgesia after intrathecal morphine does not result in improved recovery and quality of life in the first 6 months after orthopedic surgery: a randomized controlled pilot study. J Pain Res. 2017;10:1059–1069. doi:10.2147/JPR.S135142. PMID 28533694. PMC5431706.
17. Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology. 1979;50(2):149–151. doi:10.1097/00000542-197902000-00013. PMID 373503. First report of the technique in humans; case reports of respiratory depression followed within months.
18. Paterson GM, McQuay HJ, Bullingham RE, Moore RA. Intradural morphine and diamorphine. Dose response studies. Anaesthesia. 1984;39(2):113–117. doi:10.1111/j.1365-2044.1984.tb09497.x. PMID 6703265. Open study of 81 patients having major orthopedic surgery; intradural morphine 1.25 and 2.5 mg gave longer analgesia than 0.625 mg, with no dose-response for side effects.
19. Jacobson L, Chabal C, Brody MC. A dose-response study of intrathecal morphine: efficacy, duration, optimal dose, and side effects. Anesth Analg. 1988;67(11):1082–1088. doi:10.1213/00000539-198867110-00011. PMID 3189898. Double-blind study of intrathecal morphine 0, 0.3, 1 and 2.5 mg in 33 patients after total knee or hip replacement.
20. Davies GK, Tolhurst-Cleaver CL, James TL. Respiratory depression after intrathecal narcotics. Anaesthesia. 1980;35(11):1080–1083. doi:10.1111/j.1365-2044.1980.tb05047.x. PMID 6893789. Serious, delayed respiratory depression in three of six patients given 1 mg of morphine with plain bupivacaine as a subarachnoid spinal anesthetic.

IV agent selection: hypertensive emergency and rate control in atrial fibrillation

Published at /answers/iv-agents-hypertensive-emergency-afib-rate-control.

1. Jones DW, Ferdinand KC, Taler SJ, et al. 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2025;86(18):1567–1678. doi:10.1016/j.jacc.2025.05.007. PMID 40815242. (Section 6.2; Tables 26 and 27.) Correction in: J Am Coll Cardiol. 2026;87(23):3379, which changes the labetalol slow IV injection in Table 26 from every 2 min to 10-min intervals. doi:10.1016/j.jacc.2026.04.021. PMID 42300826.
2. Joglar JA, Chung MK, Armbruster AL, et al; Writing Committee Members. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2024;83(1):109–279. (Section 7.2.1, acute rate control; RACE II and diltiazem comparative data. Section 9.2, AF and heart failure; RATE-AF.) doi:10.1016/j.jacc.2023.08.017. PMID 38043043.
3. Van Gelder IC, Rienstra M, Bunting KV, et al. 2024 ESC Guidelines for the Management of Atrial Fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024;45(36):3314–3414. (Section 7.1.2, heart rate control in the acute setting; landiolol/amiodarone/digoxin options.) doi:10.1093/eurheartj/ehae176. PMID 39210723.
4. Chyou JY, Barkoudah E, Dukes JW, et al. Atrial Fibrillation Occurring During Acute Hospitalization: A Scientific Statement From the American Heart Association. Circulation. 2023;147(15):e676–e698. (Rate targets and the caution against reflexively slowing compensatory tachycardia.) doi:10.1161/CIR.0000000000001133. PMID 36912134.
5. Wigginton JG, Agarwal S, Bartos JA, et al. Part 9: Adult Advanced Life Support: 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2025;152(16_suppl_2):S538–S577. (Atrial fibrillation/flutter with rapid ventricular response; immediate electrical cardioversion for instability, and IV amiodarone for rate control in critically ill patients.) doi:10.1161/CIR.0000000000001376. PMID 41122884.
6. Syed YY. Landiolol: A Review in Tachyarrhythmias. Drugs. 2018;78(3):377–388. (Summarizing the J-LAND trial of landiolol vs digoxin in AF/flutter with LV dysfunction, NYHA III–IV, LVEF 25–50%.) doi:10.1007/s40265-018-0883-9. PMID 29470800.
7. Boulestreau R, Śpiewak M, Januszewicz A, et al. Malignant Hypertension: A Systemic Cardiovascular Disease: JACC Review Topic of the Week. J Am Coll Cardiol. 2024;83(17):1688–1701. (Recommendation to reduce mean BP by no more than ~25% in the first hours to avoid cerebral hypoperfusion.) doi:10.1016/j.jacc.2024.02.037. PMID 38658108.
8. Perrett M, Gohil N, Tica O, Bunting KV, Kotecha D. Efficacy and safety of intravenous beta-blockers in acute atrial fibrillation and flutter is dependent on beta-1 selectivity: a systematic review and meta-analysis of randomised trials. Clin Res Cardiol. 2024;113(6):831–841. doi:10.1007/s00392-023-02295-0. PMID 37658166.
9. RAPIBLYK (landiolol) for injection, for intravenous use. Prescribing information. AOP Health US, LLC. NDA 217202; initial U.S. approval November 22, 2024; pediatric patients with supraventricular tachycardia added February 13, 2026. Indicated for the short-term reduction of ventricular rate in adults with supraventricular tachycardia including atrial fibrillation and atrial flutter, and pediatric patients with supraventricular tachycardia (adults with normal cardiac function: start at 9 mcg/kg/min, maximum 36 mcg/kg/min; impaired cardiac function: start at 1 mcg/kg/min). DailyMed setid 411b0949-3a5e-2a4b-e063-6394a90abcbf. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=411b0949-3a5e-2a4b-e063-6394a90abcbf.
10. Kotecha D, Bunting KV, Gill SK, et al. Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life: The RATE-AF Randomized Clinical Trial. JAMA. 2020;324(24):2497–2508. doi:10.1001/jama.2020.23138. PMID 33351042.

Local anesthetic maximum doses

Published at /answers/local-anesthetic-maximum-doses.

1. EXPAREL (bupivacaine liposome injectable suspension) prescribing information. Pacira Pharmaceuticals. DailyMed, US National Library of Medicine, SPL set ID bb5a9e59-0f51-11df-8a39-0800200c9a66; label version published 15 December 2025. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bb5a9e59-0f51-11df-8a39-0800200c9a66. Adult infiltration maximum 266 mg; pediatric 6 to under 17 years 4 mg/kg to a maximum of 266 mg; interscalene 133 mg; sciatic in the popliteal fossa 133 mg; adductor canal 133 mg admixed with 50 mg of 0.5% bupivacaine HCl; admix ratio not to exceed 1:2; 20-minute delay after lidocaine; avoid additional local anesthetics within 96 hours; do not dilute with water or other hypotonic agents.
2. EXPAREL liposomal 266 mg/20 mL prolonged-release dispersion for injection: summary of product characteristics. Pacira Ireland Ltd. Electronic Medicines Compendium, date of revision 02/11/2022. medicines.org.uk/emc/product/14117/smpc. Admixture with lidocaine, ropivacaine, or mepivacaine causes immediate release of bupivacaine from the multivesicular liposomes.
3. EXPAREL (bupivacaine liposome injectable suspension) prescribing information, section 7 (drug interactions). Pacira Pharmaceuticals; revised 04/2018. accessdata.fda.gov/drugsatfda_docs/label/2018/022496s9lbl.pdf. The label gives the delay for lidocaine: “The administration of EXPAREL may follow the administration of lidocaine after a delay of 20 minutes or more”, adding that there are no data to support giving other local anesthetics before it. Where a topical antiseptic such as povidone iodine is applied, the site is allowed to dry first, and EXPAREL is kept out of contact with antiseptic solution.
4. Exparel (bupivacaine liposome) dosing and interactions. Medscape Reference. reference.medscape.com/drug/exparel-bupivacaine-liposome-999697. Bupivacaine HCl to liposomal ratio not to exceed 1:2; additive toxicity; no other bupivacaine formulation within 96 hours.
5. EXPAREL liposomal, European Medicines Agency product information (EPAR, Annex I). ema.europa.eu/en/documents/product-information/exparel-liposomal-epar-product-information_en.pdf. Combined liposomal plus bupivacaine HCl not to exceed 400 mg bupivacaine HCl equivalents in adults.
6. ISMP list of high-alert medications in acute care settings, January 2024, read in full 2026-09-09. ismp.org/system/files/resources/2024-01/ISMP_HighAlert_AcuteCare_List_010924_MS5760.pdf. It is a list of classes and named drugs; bupivacaine appears nowhere in it, and it attaches no rationale to any entry. Liposomal bupivacaine falls under the class “liposomal forms of drugs”, and under “epidural and intrathecal medications” where given by those routes. The propofol resemblance is from a separate document: Potential for Wrong Route Errors With Exparel, National Alert Network, 10 June 2012, reprinted in the APSF Newsletter (apsf.org/article/potential-for-wrong-route-errors-with-exparel-bupivacaine-liposome-injectable-suspension), which recommends separate storage and syringe labeling and records that neither ISMP nor the FDA had received reports of a mix-up.
7. Lee SH, Kim S, Sohn JT. Lipid emulsion treatment for local anesthetic systemic toxicity in pediatric patients: a systematic review. Medicine (Baltimore). 2024;103(11):e37534. doi:10.1097/MD.0000000000037534
8. Lipid emulsion therapy of local anesthetic systemic toxicity due to dental anesthesia. J Dent Anesth Pain Med. 2019;19(4):181–189. PMC6726891. Reports LAST prevalence of 0.27 per 1,000 and predisposing factors.
9. Weinberg G, Rupnik B, Aggarwal N, Fettiplace M, Gitman M. Local anesthetic systemic toxicity (LAST) revisited: a paradigm in evolution. APSF Newsletter. February 2020;35(1). Anesthesia Patient Safety Foundation. apsf.org/article/local-anesthetic-systemic-toxicity-last-revisited-a-paradigm-in-evolution.
10. Neal JM, Neal EJ, Weinberg GL. American Society of Regional Anesthesia and Pain Medicine local anesthetic systemic toxicity checklist: 2020 version. Reg Anesth Pain Med. 2021;46(1):81–82. doi:10.1136/rapm-2020-101986. PMID 33148630. Checklist v1.1, © 2020 ASRA Pain Medicine.
11. Lang RS, Hall-Burton D, Praslick A, Flack S. Regional anesthesia. In: Davis PJ, Cladis FP, eds. Smith’s Anesthesia for Infants and Children. 10th ed. Elsevier; 2022:522. Box 24.3 lists site absorption of local anesthetics from highest to least: intravenous, tracheal, intercostal, caudal/epidural, paracervical, lumbar epidural, brachial plexus, sciatic, subcutaneous.
12. Mather LE, Tucker GT. Properties, absorption, and disposition of local anesthetic agents. In: Cousins MJ, Carr DB, Horlocker TT, Bridenbaugh PO, eds. Cousins & Bridenbaugh’s Neural Blockade in Clinical Anesthesia and Pain Medicine. 4th ed. Lippincott Williams & Wilkins; 2009:65. Net absorption rate, independent of the agent, decreases in the order intercostal, caudal, epidural, brachial plexus, then sciatic and femoral nerve block.
13. Suresh S, Polaner DM, Coté CJ. Regional anesthesia. In: Coté CJ, Lerman J, Anderson BJ, eds. Coté and Lerman’s A Practice of Anesthesia for Infants and Children. 6th ed. Elsevier; 2019. Chapter 42, Table 42.2 and the sections on local anesthetic toxicity: amide doses reduced for infants younger than 6 months; lower alpha-1-acid glycoprotein raises the free fraction, and neonatal hepatic metabolism is immature.
14. Bourne KM, Thai S, Lei LY, et al. Patients with Ehlers-Danlos syndrome experience reduced effectiveness of lidocaine local anesthetic: a randomized cross-over clinical trial. Reg Anesth Pain Med. Published online 3 March 2026. doi:10.1136/rapm-2025-107416. PMID 41775498. 135 participants, 91 with Ehlers-Danlos syndrome and 44 healthy controls; 0.5 mL of 2% lidocaine and of saline injected subcutaneously in the forearm, with sensation tested at 5, 15 and 30 minutes.
15. 4% Citanest Plain Dental (prilocaine hydrochloride injection, USP) prescribing information. Dentsply Pharmaceutical. DailyMed, US National Library of Medicine, SPL set ID db23a56f-1e41-4843-9220-1b2e3059db41; label updated 10 November 2021. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=db23a56f-1e41-4843-9220-1b2e3059db41. Indicated for local anesthesia in dentistry by nerve block or infiltration. Maximum recommended dose within a two-hour period in normal healthy adults: 8 mg/kg under 70 kg, and 600 mg at 70 kg or more. Contraindicated in congenital or idiopathic methemoglobinemia.
16. 4% Citanest Forte Dental with epinephrine 1:200,000 (prilocaine HCl and epinephrine injection) prescribing information. Dentsply Pharmaceutical. DailyMed, US National Library of Medicine, SPL set ID 60c8710b-ae55-4fdf-e053-2991aa0adc75; label updated 29 February 2024. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=60c8710b-ae55-4fdf-e053-2991aa0adc75. The same maximum as the plain form: 8 mg/kg under 70 kg, and 600 mg at 70 kg or more, within a two-hour period in normal healthy adults. Contraindicated in congenital or idiopathic methemoglobinemia.
17. Nicks BA, Ayello EA, Woo K, Nitzki-George D, Sibbald RG. Acute wound management: revisiting the approach to assessment, irrigation, and closure considerations. Int J Emerg Med. 2010;3(4):399–407. doi:10.1007/s12245-010-0217-5. PMID 21373312. PMC3047833. Table 2, dose limitation of locally injected anesthetics: procaine 1% (10 mg/mL) 7 mg/kg, and procaine 1% with epinephrine 9 mg/kg.
18. Novocain (procaine hydrochloride injection) prescribing information. Hospira, Inc. DailyMed, US National Library of Medicine, SPL set ID c80c810a-60e0-49bd-139c-95aec3a286fc; label updated 16 April 2007. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c80c810a-60e0-49bd-139c-95aec3a286fc. Indicated for local infiltration and peripheral nerve block. For infiltration, 350 mg to 600 mg is generally considered a single safe total dose, and the usual total dose during one treatment should not exceed 1,000 mg.
19. Polocaine (mepivacaine hydrochloride injection) prescribing information. DailyMed, US National Library of Medicine. Adult single-dose ceiling generally 400 mg; doses up to approximately 550 mg (about 7 mg/kg) only in exceptional circumstances; total dose should not exceed 1,000 mg in 24 hours; pediatric limit 5–6 mg/kg; epinephrine does not raise the ceiling.
20. Waldinger R, Weinberg G, Gitman M. Local anesthetic toxicity in the geriatric population. Drugs Aging. 2020;37(1):1–9. Reviews the sodium-channel and mitochondrial mechanisms of LAST, the relative cardiotoxicity of bupivacaine, the aggravating role of hypoxia and acidosis, and the reported range of LAST incidence across settings.
21. Boretsky KR. A review of regional anesthesia in infants. Paediatr Drugs. 2019;21(6):439–449. Pediatric Regional Anesthesia Network (PRAN) data: infants a disproportionate share of reported LAST events relative to their share of blocks, with penile block a leading setting in infants.
22. Jiang S, Tang M. Allergy to local anesthetics is a rarity: review of diagnostics and strategies for clinical management. Clin Rev Allergy Immunol. 2023. True IgE-mediated allergy is rare; ester agents are metabolized to para-aminobenzoic acid (PABA) with intra-class cross-reactivity, amides rarely cause true allergy; preservatives (methylparaben) and metabisulfite antioxidants, and epinephrine effects, account for many reactions mislabeled as allergy.
23. Eggleston ST, Lush LW. Understanding allergic reactions to local anesthetics. Ann Pharmacother. 1996;30(7–8):851–857. Ester versus amide classification, PABA as the relevant ester allergen, and the low cross-reactivity of amides.
24. Sequeira A. An approach to heparin and lidocaine hypersensitivity for the interventional nephrologist. Semin Dial. 2014;27(3):308–312. Methylparaben in multidose local anesthetic vials as a frequent sensitizer, and its absence from single-dose preservative-free preparations.
25. Henkel ED, Haller CN, Diaz LZ, et al. Optimizing pediatric periprocedural pain management part I—evolving ethics and topical anesthetics. Pediatr Dermatol. 2023. Preservative content of local anesthetic preparations, including methylparaben, and its relevance to reported reactions.
26. El-Boghdadly K, Chin KJ. Local anesthetic systemic toxicity: continuing professional development. Can J Anaesth. 2016;63(3):330–349. Voltage-gated sodium channel blockade as the core mechanism, biphasic CNS toxicity, bupivacaine cardiotoxicity from high-affinity slow-dissociating channel binding plus mitochondrial impairment, and the worsening effect of hypoxia and acidosis.

Mast cell activation syndrome and anesthesia

Published at /answers/mcas-and-anesthesia.

1. Chopra P, Bluestein L. Perioperative care in patients with Ehlers Danlos syndromes. Open Journal of Anesthesiology. 2020;10(1):13–29. doi:10.4236/ojanes.2020.101002. Review covering coexisting mast cell activation syndrome, dysautonomia and gastroparesis. Sources the recommendations to avoid histamine-releasing agents, to prefer induction agents with minimal hemodynamic change such as etomidate or ketamine, and to use fentanyl, sufentanil or ketamine for analgesia without histamine release.
2. Zhu LJ, Liu AY, Wong PH, Arroyo AC. Road less traveled: drug hypersensitivity to fluoroquinolones, vancomycin, tetracyclines, and macrolides. Clin Rev Allergy Immunol. 2022;62(3):505–518. doi:10.1007/s12016-021-08919-5. PMID 35092578. Source of the vancomycin mechanism: the vancomycin infusion reaction, previously called red man syndrome, is caused by infusion rate-dependent direct mast cell degranulation, with MRGPRX2 implicated and IgE-mediated reactions rare.
3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Systemic Mastocytosis. 2026.
4. Naguib M, Samarkandi AH, Bakhamees HS, Magboul MA, el-Bakry AK. Histamine-release haemodynamic changes produced by rocuronium, vecuronium, mivacurium, atracurium and tubocurarine. Br J Anaesth. 1995;75(5):588–592.
5. McNeil BD, Pundir P, Meeker S, et al. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature. 2015;519(7542):237–241.
6. Navinés-Ferrer A, Serrano-Candelas E, Lafuente A, et al. MRGPRX2-mediated mast cell response to drugs used in perioperative procedures and anaesthesia. Sci Rep. 2018;8:11628.
7. Aziz Q, Harris LA, Goodman BP, Simrén M, Shin A. AGA clinical practice update on GI manifestations and autonomic or immune dysfunction in hypermobile Ehlers-Danlos syndrome: expert review. Clin Gastroenterol Hepatol. 2025.
8. Farley M, Estrada-Mendizabal RJ, Gansert EA, et al. Prevalence of mast cell activation disorders and hereditary alpha tryptasemia among patients with postural orthostatic tachycardia syndrome and Ehlers-Danlos syndrome: a systematic review. Ann Allergy Asthma Immunol. 2025.
9. Requena López S, Matito A, Alvarez-Twose I, Torrelo A. Perioperative anaphylaxis in a patient with a solitary mastocytoma. Pediatr Dermatol. 2019.
10. Dodd A, Turner PJ, Soar J, Savic L. Emergency treatment of peri-operative anaphylaxis: Resuscitation Council UK algorithm for anaesthetists. Anaesthesia. 2024.
11. Garvey LH, Dewachter P, Hepner DL, et al. Management of suspected immediate perioperative allergic reactions: an international overview and consensus recommendations. Br J Anaesth. 2019;123(1):e50–e64.
12. Kačar M, Rijavec M, Šelb J, Korošec P. Clonal mast cell disorders and hereditary α-tryptasemia as risk factors for anaphylaxis. Clin Exp Allergy. 2023.
13. Yao L, Subramaniam K, Raja KM, et al. Association of postural orthostatic tachycardia syndrome, hypermobility spectrum disorders, and mast cell activation syndrome in young patients; prevalence, overlap and response to therapy depends on the definition. Front Neurol. 2024.
14. Schaffer JV. Pediatric mastocytosis: recognition and management. Am J Clin Dermatol. 2021.
15. van der Weide HY, van Westerloo DJ, van den Bergh WM. Critical care management of systemic mastocytosis: when every wasp is a killer bee. Crit Care. 2015;19:238.
16. Castells M, Giannetti MP, Hamilton MJ, et al. Mast cell activation syndrome: current understanding and research needs. J Allergy Clin Immunol. 2024.
17. Weiler CR, Austen KF, Akin C, et al. AAAAI Mast Cell Disorders Committee work group report: mast cell activation syndrome (MCAS) diagnosis and management. J Allergy Clin Immunol. 2019;144(4):883–896.

Further reading, not cited in the text:

• Solomon BD, Khatri P. Clustering of clinical symptoms using large language models reveals low diagnostic specificity of proposed alternatives to consensus mast cell activation syndrome criteria. J Allergy Clin Immunol. 2025.
• Laserna A, Nishtar M, Vidovich C, Borovcanin Z. Perioperative management of Ehlers-Danlos type III syndrome associated with postural orthostatic tachycardia in patients undergoing general anesthesia. Cureus. 2021;13(11):e19311. doi:10.7759/cureus.19311
• Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8–26.

Methemoglobinemia: recognition and treatment

Published at /answers/methemoglobinemia.

1. Methemoglobinemia. OpenAnesthesia. openanesthesia.org/keywords/methemoglobinemia. Covers the ferrous-to-ferric mechanism, the leftward shift of the oxygen-dissociation curve, causative agents including prilocaine and benzocaine, and rebound within 18 hours from lipid-soluble agents.
2. Methemoglobinemia. WikEM. wikem.org/wiki/Methemoglobinemia. Methylene blue 1–2 mg/kg over 5 minutes; saturation gap greater than 5%; sulfhemoglobin misidentified by conventional co-oximetry; and a level-symptom table. Contraindicates methylene blue in G6PD deficiency and names ascorbic acid as the substitute.
3. Methemoglobinemia. StatPearls, NCBI Bookshelf, updated December 2025. Bookshelf ID NBK537317. Methylene blue 1–2 mg/kg (0.1–0.2 mL/kg of 1% solution) IV over 5 minutes, repeatable after 30–60 minutes; the absorbance ratio and displayed SpO₂ of 85%; the NADPH-MetHb reductase pathway and its dependence on G6PD; the statement that G6PD deficiency being a risk factor for methemoglobinemia is a misconception; the position that methylene blue use in G6PD deficiency is controversial but not contraindicated, with hemolysis observed at doses exceeding 5 mg/kg; and the monoamine oxidase inhibitor property.
4. Methemoglobinemia. EMCrit Internet Book of Critical Care. emcrit.org/ibcc/methemoglobinemia.
5. Methemoglobinemia. ScienceDirect topic overview. sciencedirect.com/topics/medicine-and-dentistry/methemoglobinemia. Cumulative methylene blue ceiling of 7 mg/kg, response within 30 minutes, and recrudescent methemoglobinemia with dapsone.
6. Methemoglobinemia: when to suspect and how to treat. Curr Med Issues. doi:10.4103/cmi.cmi_55_19. Supportive care, repeat dosing after 1 hour if methemoglobin remains above 20%.
7. Iolascon A, Bianchi P, Andolfo I, et al. Recommendations for diagnosis and treatment of methemoglobinemia. Am J Hematol. 2021;96(12):1666–1678. doi:10.1002/ajh.26340. PMID 34467556. PMC9291883. Methylene blue 1–2 mg/kg (0.2 mL/kg of a 1% solution) IV over three to five minutes, repeatable at 1 mg/kg if the level has not fallen substantially within 30 to 60 minutes; glucose required to generate NADPH; guanylate cyclase inhibition with systemic and pulmonary hypertension; and the note that methylene blue is contraindicated in G6PD deficiency because its action as an electron carrier depends on NADPH generated by G6PD through the hexose monophosphate shunt.
8. Methemoglobinemia treatment and management. Medscape. emedicine.medscape.com/article/204178-treatment. Notes methylene blue ineffectiveness in G6PD deficiency and hemoglobin M, the approximately 2% US prevalence of G6PD deficiency with no routine testing recommendation, maintenance glucose, and second-line options.
9. ProvayBlue (methylene blue) injection prescribing information. American Regent, Inc. DailyMed, US National Library of Medicine, SPL set ID 4f6848e5-35ed-4046-b13c-3032b5ba3232; label version published 12 June 2025. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4f6848e5-35ed-4046-b13c-3032b5ba3232. Contraindicated in G6PD deficiency; hemolytic anemia with onset possibly delayed a day or more; pulse oximetry underestimation; reported fall in Bispectral Index.
10. Chen B, Han Y. Co-occurrence of acute hemolytic anemia and methemoglobinemia in a 74-year-old female with G6PD deficiency: a case report. Medicine (Baltimore). 2025. doi:10.1097/MD.0000000000042826. Hemoglobin fell from 81 to 38 g/L after methylene blue; replaced with vitamin C and methylprednisolone.
11. Vallurupalli S. Methemoglobinemia due to topical pharyngeal anesthesia during endoscopic procedures. Local Reg Anesth. 2010;3:137–142. doi:10.2147/LRA.S12227. PMID 22915882. PMC3417961. Reported incidence of benzocaine methemoglobinemia of 0.067% to 0.45% during transesophageal echocardiography, from retrospective series.
12. Filipiak-Strzecka D, Kasprzak JD, Wiszniewska M, Walusiak-Skorupa J, Lipiec P. The influence of lidocaine topical anesthesia during transesophageal echocardiography on blood methemoglobin level and risk of methemoglobinemia. Int J Cardiovasc Imaging. 2015;31(4):727–731. doi:10.1007/s10554-015-0608-z. PMID 25663608. PMC4428890. No clinically evident methemoglobinemia in 3,354 transesophageal echocardiograms performed over 13 years with 10% lidocaine spray as the topical anesthetic.
13. US Food and Drug Administration. Risk of serious and potentially fatal blood disorder prompts FDA action on oral over-the-counter benzocaine products used for teething and mouth pain and prescription local anesthetics. Drug Safety Communication, 23 May 2018. The fda.gov page is no longer available; archived copy: web.archive.org copy of fda.gov. States that the FDA is requiring a standardized methemoglobinemia warning in the prescribing information of all prescription local anesthetics, and that it urged manufacturers of over-the-counter oral benzocaine products for adults and children 2 years and older to add a warning about methemoglobinemia to their labels.
14. Guay J. Methemoglobinemia related to local anesthetics: a summary of 242 episodes. Anesth Analg. 2009;108(3):837–845. doi:10.1213/ane.0b013e318187c4b1. PMID 19224791. Plain prilocaine may induce clinically symptomatic methemoglobinemia in children older than 6 months at doses above 2.5 mg/kg; in adults the dose should be kept below 5.0 mg/kg; prilocaine should not be used in infants younger than 6 months, in pregnancy, or with other oxidizing drugs.
15. 4% Citanest Plain Dental (prilocaine hydrochloride injection, USP) prescribing information. Dentsply Pharmaceutical. DailyMed, US National Library of Medicine, SPL set ID db23a56f-1e41-4843-9220-1b2e3059db41; label updated 10 November 2021. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=db23a56f-1e41-4843-9220-1b2e3059db41. Maximum recommended dose within a two-hour period in normal healthy adults: 8 mg/kg under 70 kg, and 600 mg at 70 kg or more. The development of methemoglobinemia is generally dose related but may occur at any dose in susceptible individuals.
16. 4% Citanest Forte Dental with epinephrine 1:200,000 (prilocaine HCl and epinephrine injection) prescribing information. Dentsply Pharmaceutical. DailyMed, US National Library of Medicine, SPL set ID 60c8710b-ae55-4fdf-e053-2991aa0adc75; label updated 29 February 2024. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=60c8710b-ae55-4fdf-e053-2991aa0adc75. The same maximum and the same statement on methemoglobinemia as the plain form.
17. Twine AJ, Rees DC. Methaemoglobinaemia: from pathophysiology to contemporary clinical management. Br J Haematol. 2026. Contemporary review: the saturation gap should be considered supportive rather than a universal hallmark, citing a 2022 systematic review of acquired cases in which an SaO₂:SpO₂ ratio >1 was not consistently present; pulse oximetry fixed around 85% once methemoglobin exceeds ~15–20%, plateauing by >35%; a level-symptom ordering (cyanosis 15–20%, neurological symptoms 20–45%, coma/seizure/arrhythmia 55–70%, death >70%); methylene blue contraindicated in G6PD deficiency; and recrudescence from hydroxylamine-metabolite recycling with dapsone, with cimetidine/P450 inhibition as an adjunct.
18. Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning. Circulation. 2023. Methylene blue as first-line for symptomatic methemoglobinemia, with exchange transfusion, hyperbaric oxygen and ascorbic acid as adjuncts or alternatives, and the note that N-acetylcysteine is not effective.
19. Cao D, Arens AM, Chow SL, et al. Part 10: adult and pediatric special circumstances of resuscitation: 2025 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2025. Reaffirms methylene blue as first-line for symptomatic methemoglobinemia, with exchange transfusion, hyperbaric oxygen and ascorbic acid as alternatives, and that N-acetylcysteine is ineffective.
20. Schmidt EP, Shepard JO, Liu L. Case 11-2023: a 67-year-old man with mantle-cell lymphoma and hypoxemia. N Engl J Med. 2023. Documents the pulse-oximetry plateau, with SpO₂ ranging minimally from about 83 to 87% across a broad span of methemoglobin levels, and symptomatic methemoglobinemia at fractions as low as ~8% with concurrent anemia.
21. Williams RT, Fischer BG. Benzocaine-induced methemoglobinemia after nasogastric tube insertion. JAMA Intern Med. 2025. Teachable-moment analysis reporting an inpatient incidence of about 1 in 730 benzocaine exposures and a 3.7-fold higher risk with benzocaine than lidocaine, with inpatient status, active infection and anemia as risk factors.
22. Methylene blue injection prescribing information. US Food and Drug Administration / DailyMed. Recommends 1 mg/kg IV over 5–30 minutes, a single repeat dose of up to 1 mg/kg at 1 hour if methemoglobin remains above 30%, and a maximum of two doses before switching to alternative therapy.

Perioperative steroid stress dosing: what’s current

Published at /answers/perioperative-steroid-stress-dosing.

1. Beuschlein F, Else T, Bancos I, et al. European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-Induced Adrenal Insufficiency. J Clin Endocrinol Metab. 2024;109(7):1657–1683. PMID 38724043. Table 8: perioperative and stress-dose regimens; high-maintenance-dose exemptions.
2. Woodcock T, Barker P, Daniel S, et al. Guidelines for the management of glucocorticoids during the peri-operative period for patients with adrenal insufficiency: guidelines from the Association of Anaesthetists, the Royal College of Physicians and the Society for Endocrinology UK. Anaesthesia. 2020;75(5):654–663. doi:10.1111/anae.14963. PMID 32017012.
3. Vaidya A, Findling J, Bancos I. Adrenal Insufficiency in Adults: A Review. JAMA. 2025;334(8). Table 3 reproduces the ESE/Endocrine Society perioperative stress-dose regimen.
4. Goodman SM, Springer B, Guyatt G, et al. 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. Arthritis Rheumatol. 2017;69(8):1538–1551. PMID 28620948. Continue current daily dose (≤16 mg/day prednisone equivalent) rather than stress dosing; excludes primary adrenal insufficiency/hypothalamic disease.
5. Marik PE, Varon J. Requirement of perioperative stress doses of corticosteroids: a systematic review of the literature. Arch Surg. 2008;143(12):1222–1226. PMID 19075176.
6. Chen Cardenas SM, Santhanam P, Morris-Wiseman L, Salvatori R, Hamrahian AH. Perioperative evaluation and management of patients on glucocorticoids. J Endocr Soc. 2022;7(2):bvac185. doi:10.1210/jendso/bvac185. PMID 36545644.
7. Martin-Grace J, Tomkins M, O’Reilly MW, Sherlock M. Iatrogenic adrenal insufficiency in adults. Nat Rev Endocrinol. 2024;20(4):209–227. PMID 38272995. Risk stratification for HPA suppression: high-risk dose/duration thresholds by route, and discontinuation within the previous 12 months as a moderate-risk category.
8. Salem M, Tainsh RE Jr, Bromberg J, Loriaux DL, Chernow B. Perioperative glucocorticoid coverage. A reassessment 42 years after emergence of a problem. Ann Surg. 1994;219(4):416–425. doi:10.1097/00000658-199404000-00013. PMID 8161268. The minor, moderate and major targets, the operations named in each tier, and the worked examples.
9. Chilkoti GT, Singh A, Mohta M, Saxena AK. Perioperative “stress dose” of corticosteroid: pharmacological and clinical perspective. J Anaesthesiol Clin Pharmacol. 2019;35(2):147–152. doi:10.4103/joacp.JOACP_242_17. PMID 31303699. Its Table 3 is the source of the 25 mg hydrocortisone at induction for minor surgery, of the 100 mg per day added for moderate and major surgery, and of the >10 mg prednisolone threshold that table applies to.
10. The management of the surgical patient taking glucocorticoids. UpToDate. Accessed September 2026. uptodate.com/contents/the-management-of-the-surgical-patient-taking-glucocorticoids. Describes the historic 300 mg/day practice and its 1950s origin, and summarizes the randomized trial in major colorectal surgery comparing high- and low-dose regimens.
11. Wulff TL, Hjortrup PB, Meyhoff TS, et al. Perioperative glucocorticoid stress dose for adult surgical patients at risk of adrenal insufficiency (protocol). Cochrane Database Syst Rev. 2023. doi:10.1002/14651858.CD015241. PMC10440999. New protocol registered in 2023; the earlier review (Yong SL, Coulthard P, Wrzosek A. Supplemental perioperative steroids for surgical patients with adrenal insufficiency) was withdrawn in 2012 for an insufficient evidence base.
12. Peri-operative guidance for patients with or at risk of adrenal insufficiency. NHS Highland adult therapeutic guidelines, Right Decisions. Document TAM452, version 2.1, last reviewed 28 August 2025. rightdecisions.scot.nhs.uk. Infusion-versus-bolus preference, fludrocortisone guidance, hyponatraemia note.
13. Adrenal insufficiency and perioperative corticosteroids. OpenAnesthesia. Accessed September 2026. openanesthesia.org/keywords/adrenal-insufficiency-and-perioperative-corticosteroids. Summarizes the dose and duration thresholds used for the suppression-likelihood table and the HPA testing recommendation.
14. Perioperative stress dose guidelines. Stanford Department of Pediatric Anesthesia. med.stanford.edu/.../perioperative-stress-dose-guidelines.pdf. Accessed September 2026. Notes that HPA axis recovery after the last steroid dose is greatest in the first 3–6 months and may take up to a year.
15. Dexamethasone and prednisolone sodium phosphate. US Food and Drug Administration prescribing information. Accessed 2026. Glucocorticoid potency equivalence table (oral/IV): hydrocortisone 20 mg ≈ cortisone 25 mg ≈ prednisolone/prednisone 5 mg ≈ methylprednisolone/triamcinolone 4 mg ≈ dexamethasone/betamethasone 0.75 mg. Relative potencies apply to oral or IV administration and change with IM or intra-articular injection.
16. Goodman SM, Springer BD, Chen AF, et al. 2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. Arthritis Care Res (Hoboken). 2022;74(9):1399–1408. doi:10.1002/acr.24893. Updates reference 4; continues to recommend the current daily glucocorticoid dose rather than stress dosing.

POTS and anesthesia: a perioperative guide

Published at /answers/pots-and-anesthesia.

1. Laserna A, Nishtar M, Vidovich C, Borovcanin Z. Perioperative management of Ehlers-Danlos type III syndrome associated with postural orthostatic tachycardia in patients undergoing general anesthesia. Cureus. 2021;13(11):e19311. doi:10.7759/cureus.19311. Source of the diagnostic definition, of preoperative evaluation and intravenous hydration before sedative or anesthetic medication, of careful positioning at induction, of gentle emergence and extubation, and of the handover to recovery staff covering position changes and vital sign fluctuations. It does not address neuraxial technique.
2. Aljuba YM, Shatalin D, Ronenson A, Grenader A, Ioscovich A. Anesthetic management of a pregnant patient with Ehlers-Danlos syndrome undergoing elective cesarean delivery: a case report. Cureus. 2025;17(8):e89400. doi:10.7759/cureus.89400. Describes extended post-anesthesia observation in a patient with POTS among multiple comorbidities.
3. Corbett WL, Reiter CM, Schultz JR, Kanter RJ, Habib AS. Anaesthetic management of a parturient with the postural orthostatic tachycardia syndrome: a case report. Br J Anaesth. 2006;97(2):196–199. doi:10.1093/bja/ael105. PMID 16698864. Source of the early epidural and of slow titration after an adequate fluid preload to minimize hypotension and the subsequent tachycardia. Abstract read; the full text is subscription-only.
4. Powless CA, Harms RW, Watson WJ. Postural tachycardia syndrome complicating pregnancy. J Matern Fetal Neonatal Med. 2010;23(8):850–853. doi:10.3109/14767050903265089. PMID 20136369. Nine pregnancies in seven women with POTS; epidural anesthesia in five of seven vaginal deliveries without associated complications, concluding that regional anesthesia can be undertaken safely. Abstract read; the full text is subscription-only.
5. Sarin A, Chen LL, Wick EC. Enhanced recovery after surgery—preoperative fasting and glucose loading—a review. J Surg Oncol. 2017;116(5):578–582. doi:10.1002/jso.24810. PMID 28846137. Source of fasts of 12 hours or more under a nothing-by-mouth-after-midnight policy and operating room delays, and of prolonged fasting depriving patients of hydration.
6. American Society of Anesthesiologists Task Force on Preoperative Fasting. Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: application to healthy patients undergoing elective procedures. Anesthesiology. 2017;126(3):376–393. doi:10.1097/ALN.0000000000001452. PMID 28045707. Source of the two-hour clear-liquid interval. Its recommendations are written for healthy patients having elective procedures.
7. Chung TH, Raj SR. Postural orthostatic tachycardia syndrome (POTS): a review. JAMA. 2026. Current diagnostic criteria, including the ≥40 beats/min threshold for individuals aged 12–19 years and the requirement for symptoms ≥3 months without orthostatic hypotension; also the contemporary overview of workup and treatment. Does not address perioperative management.
8. Joshi GP, Abdelmalak BB, Weigel WA, et al. 2023 American Society of Anesthesiologists practice guidelines for preoperative fasting: carbohydrate-containing clear liquids with or without protein, chewing gum, and pediatric fasting duration—a modular update of the 2017 guidelines. Anesthesiology. 2023;138(2):132–151. Reaffirms clear liquids until 2 h to minimize the harms of prolonged fasting; notes some comorbidities traditionally believed to delay gastric emptying may have little effect.
9. Rüggeberg A, El-Boghdadly K, Bilotta F, et al. Peri-operative fasting in adults: an international, multidisciplinary consensus statement. Anaesthesia. 2026. PMID 41657234. Recommends encouraging clear liquids until 2 h and implementing institutional protocols that allow more liberal clear-liquid intake at <2 h before anesthesia or sedation.
10. Robbins NM, Golden EP, Freeman KC, et al. Approach to postural orthostatic tachycardia syndrome. Neurol Clin Pract. 2026. First-line pharmacotherapy and dosing: midodrine (tachyphylaxis; avoid round-the-clock dosing), fludrocortisone (hypokalemia; potassium supplementation), and ivabradine (photopsias; contraception required in people of childbearing potential).
11. Katz J, Angeli AM, Alicea A, Austin K. Gastrointestinal manifestations and nutrition support in hypermobile Ehlers-Danlos, postural orthostatic tachycardia, and mast cell activation syndromes. Curr Gastroenterol Rep. 2026. In POTS, studies show both delayed (~18%) and rapid (up to 48%) gastric emptying; hEDS/HSD have increased prevalence of gastroparesis versus controls.
12. Kulin D, Holtmann G, Fairlie T, et al. Meta-analysis: chronic gastrointestinal symptoms and comorbidities in hypermobile Ehlers–Danlos syndrome and hypermobility spectrum disorders. Aliment Pharmacol Ther. 2026. One-third of hEDS/HSD patients have orthostatic intolerance; nearly 20% are diagnosed with POTS.
13. Aziz Q, Harris LA, Goodman BP, Simrén M, Shin A. AGA clinical practice update on GI manifestations and autonomic or immune dysfunction in hypermobile Ehlers-Danlos syndrome: expert review. Clin Gastroenterol Hepatol. 2025. In a survey of 616 hEDS/HSD patients, 37.5% reported a POTS diagnosis; overlapping MCAS/POTS/EDS figures reported.
14. Cornwell WK, Levine BD, Baptiste D, et al. Exercise intolerance and response to training in patients with postacute sequelae of SARS-CoV-2 (Long COVID): a scientific statement from the American Heart Association. Circulation. 2025. POTS typically follows an inciting event (infection, surgery, enforced bed rest) with a deconditioning spiral; may coexist with EDS and other conditions.
15. Zadourian A, Doherty TA, Swiatkiewicz I, Taub PR. Postural orthostatic tachycardia syndrome: prevalence, pathophysiology, and management. Drugs. 2018;78(10):983–994. Lists drugs that may cause or worsen orthostatic intolerance; nonselective beta-blockers such as propranolol may particularly benefit the hyperadrenergic subtype.
16. U.S. Food and Drug Administration. Orange Book: approved drug products with therapeutic equivalence evaluations. Source of the Corlanor (ivabradine) brand-discontinuation status in the United States.

Further reading, not cited in the text:

• Perioperative care in patients with Ehlers-Danlos syndromes. Review covering coexisting dysautonomia, mast cell activation syndrome and gastroparesis, and the intraoperative implications of each.

Rocuronium vs succinylcholine for RSI

Published at /answers/rocuronium-vs-succinylcholine-rsi.

1. Tran DTT, Newton EK, Mount VAH, Lee JS, Wells GA, Perry JJ. Rocuronium vs. succinylcholine for rapid sequence intubation: a Cochrane systematic review. Anaesthesia. 2017;72(6):765–777. PMID 28654173. Fifty trials, 4,151 participants.
2. Tran DTT, Newton EK, Mount VAH, et al. Rocuronium versus succinylcholine for rapid sequence induction intubation. Cochrane Database Syst Rev. 2015;10:CD002788. PMID 26512948. Excellent conditions RR 0.86 (0.81–0.92, n = 4151); clinically acceptable RR 0.97 (0.95–0.99, n = 3992, 48 trials); succinylcholine superior against rocuronium 0.6–0.7 mg/kg, and no statistical difference against 0.9–1.0 mg/kg or 1.2 mg/kg (3 trials, 86 participants), with the authors’ reasoning that succinylcholine remains “clinically superior as it has a shorter duration of action.” Also the source of the 37–72 minute duration at standard doses and 73 ± 32 minutes at 1.2 mg/kg.
3. Rocuronium vs. succinylcholine for rapid sequence intubation. TheNNT review of the Cochrane analysis. thennt.com/nnt/rocuronium-vs-succinylcholine-rapid-sequence-intubation. Reports the ARR of 12% and NNT of 8, the contraindication list, the duration figures of 6–10 minutes for succinylcholine and 37–72 minutes for rocuronium (a range it does not tie to a dose), and 0.9–1.0 mg/kg as the recommended higher dose of rocuronium.
4. Marsch SC, Steiner L, Bucher E, et al. Succinylcholine versus rocuronium for rapid sequence intubation in intensive care: a prospective, randomized controlled trial. Crit Care. 2011;15:R199. doi:10.1186/cc10367. 401 critically ill patients.
5. Intubating conditions during rapid sequence induction with either rocuronium or suxamethonium in elderly patients: a randomised study. PMC11798891. Excellent intubating conditions 73% versus 75% (p = 0.82).
6. Benumof JL, Dagg R, Benumof R. Critical hemoglobin desaturation will occur before return to an unparalyzed state following 1 mg/kg intravenous succinylcholine. Anesthesiology. 1997;87(4):979–982. doi:10.1097/00000542-199710000-00034. PMID 9357902.
7. Sørensen MK, Bretlau C, Gätke MR, Sørensen AM, Rasmussen LS. Rapid sequence induction and intubation with rocuronium–sugammadex compared with succinylcholine: a randomized trial. Br J Anaesth. 2012;108(4):682–689. doi:10.1093/bja/aer503. PMID 22315329. Time to spontaneous ventilation 216 vs 406 s; includes the authors’ reply to correspondence clarifying the can’t-intubate-can’t-ventilate limitation.
8. Sørensen MK, et al., as above — Br J Anaesth. 2012;108(4):682–689. doi:10.1093/bja/aer503. PMID 22315329 — on the adverse effect profile of succinylcholine: bradycardia, asystole, plasma potassium elevation and muscle ache.
9. Comparison of intubating conditions following administration of low-dose rocuronium or succinylcholine in adults: a randomized double blind study. PMC4173439. Notes rocuronium’s onset comparable to succinylcholine above 0.9 mg/kg and its lack of cardiovascular effect or histamine release.
10. Guihard B, Chollet-Xémard C, Lakhnati P, et al. Effect of rocuronium vs succinylcholine on endotracheal intubation success rate among patients undergoing out-of-hospital rapid sequence intubation (CURASMUR): a randomized clinical trial. JAMA. 2019;322(23):2303–2312. PMID 31846014. 1,248 patients; first-pass success 79.4% (succinylcholine) vs 74.6% (rocuronium 1.2 mg/kg); rocuronium did not meet noninferiority (difference −4.8%, one-sided 97.5% CI −9% to ∞; margin 7%).
11. Acquisto NM, Mosier JM, Bittner EA, et al. Society of Critical Care Medicine clinical practice guidelines for rapid sequence intubation in the critically ill adult patient. Crit Care Med. 2023;51(10):1411–1430. First-pass success not significantly different between agents; addresses awareness with paralysis and post-intubation sedation.
12. Succinylcholine chloride injection. US FDA prescribing information (Anectine and generics), 2023–2025. DailyMed (Anectine). Contraindications: hypersensitivity to the drug; personal or familial history of malignant hyperthermia; skeletal muscle myopathies; and clinical states in which hyperkalemia would be aggravated (after the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury). Anaphylaxis/hypersensitivity reactions are reported and are more frequently associated with succinylcholine than with rocuronium.
13. Heier T, Feiner JR, Lin J, Brown R, Caldwell JE. Hemoglobin desaturation after succinylcholine-induced apnea: a study of the recovery of spontaneous ventilation in healthy volunteers. Anesthesiology. 2001;94(5):754–759. PMID 11388524. After succinylcholine 1 mg/kg apnea, SpO₂ fell below 95% in roughly half and below 80% in about a third of subjects before spontaneous ventilation returned.
14. Hayes AH, Breslin DS, Mirakhur RK, Reid JE, O'Hare RA. Frequency of haemoglobin desaturation with the use of succinylcholine during rapid sequence induction of anaesthesia. Acta Anaesthesiol Scand. 2001;45(6):746–749. PMID 11421834. 11% of patients desaturated to ≤90% before spontaneous ventilation returned, regardless of preoxygenation technique.
15. Lee C, Jahr JS, Candiotti KA, et al. Reversal of profound neuromuscular block by sugammadex administered three minutes after rocuronium: a comparison with spontaneous recovery from succinylcholine. Anesthesiology. 2009;110(5):1020–1025. PMID 19387176. Rocuronium 1.2 mg/kg reversed with sugammadex 16 mg/kg three minutes later recovered faster than spontaneous recovery from succinylcholine 1 mg/kg.
16. Tang L, Li S, Huang S, Ma H, Wang Z. Desaturation following rapid sequence induction using succinylcholine vs. rocuronium in overweight patients. Acta Anaesthesiol Scand. 2011;55(2):203–208. doi:10.1111/j.1399-6576.2010.02365.x. PMID 21226862. Safe apnea time 283 s (succinylcholine) vs 329 s (rocuronium); succinylcholine produced faster desaturation and slower recovery.
17. Sugammadex (Bridion) injection. US FDA prescribing information, 2026. DailyMed (Bridion). The 16 mg/kg dose is indicated for immediate reversal of neuromuscular blockade after a single dose of rocuronium 1.2 mg/kg; 16 mg/kg for an 80 kg patient is 1,280 mg.
18. DeMasi SC, Casey JD, Semler MW. Evidence-based emergency tracheal intubation. Am J Respir Crit Care Med. 2025. Discusses agent selection for RSI and the risk of accidental awareness with paralysis when longer-acting agents are used without adequate post-intubation sedation.
19. Ko CL, Celmins L. Pharmacology for rapid sequence intubation (RSI): airway management in trauma patients. JOMI. 2024. Succinylcholine is generally considered safe in the initial ~24–48 hours after major burn or denervating injury; hyperkalemia risk develops as upregulation of extrajunctional acetylcholine receptors progresses (roughly 3–5 days after injury, peaking ~7–10 days after burns).

Spinal anesthesia in elderly patients

Published at /answers/spinal-anesthesia-elderly-patients.

1. Neuman MD, Feng R, Carson JL, et al; REGAIN Investigators. Spinal anesthesia or general anesthesia for hip surgery in older adults. N Engl J Med. 2021;385(22):2025–2035. doi:10.1056/NEJMoa2113514. PMID 34623788
2. Neuman MD, Ellenberg SS, Sieber FE, et al. Comparing two types of anesthesia for hip fracture surgery — the REGAIN trial. Patient-Centered Outcomes Research Institute; July 2023. Bookshelf ID NBK618691. doi:10.25302/07.2023.pcs.140618876. PMID 41118476. Reports in-hospital secondary outcomes including death, acute kidney injury, and critical care admission.
3. Neuman MD, Feng R, Ellenberg SS, et al. Pain, analgesic use, and patient satisfaction with spinal versus general anesthesia for hip fracture surgery: a randomized clinical trial. Ann Intern Med. 2022;175(7):952–960. PMID 35696684
4. Li T, Li J, Yuan L, et al. Effect of regional vs general anesthesia on incidence of postoperative delirium in older patients undergoing hip fracture surgery: the RAGA randomized trial. JAMA. 2022;327(1):50–58. doi:10.1001/jama.2021.22647
5. Outcomes with spinal versus general anesthesia for patients with and without preoperative cognitive impairment: secondary analysis of a randomized clinical trial. PMID 37170754
6. White SM, Tedore T, Shelton CL. There is (probably) no (meaningful) difference in (most) outcomes between spinal and general anaesthesia for hip fracture surgery: time to move forward. Br J Anaesth. 2023;130(4):385–389. doi:10.1016/j.bja.2023.01.013. PMID 36801101.
7. Comparing two different norepinephrine infusion rates for prophylaxis against spinal-induced hypotension in the elderly. ClinicalTrials.gov NCT07077265. A non-inferiority comparison of norepinephrine 0.07 against 0.1 mcg/kg/min; now published (see ref 14). The registry record carries no incidence figure and none is attributed to it here.
8. Hofhuizen C, Lemson J, Snoeck M, Scheffer GJ. Spinal anesthesia-induced hypotension is caused by a decrease in stroke volume in elderly patients. Local Reg Anesth. 2019;12:19–26. doi:10.2147/LRA.S193925. PMID 30881108. PMC6404676.
9. Hypotension from spinal anesthesia in patients aged greater than 80 years is due to a decrease in systemic vascular resistance. PMID 22537572
10. Neal JM. Hypotension and bradycardia during spinal anesthesia: significance, prevention, and treatment. Tech Reg Anesth Pain Manag. 2000;4(4):148–154. doi:10.1053/trap.2000.20600.
11. Ferré F, Martin C, Bosch L, Kurrek M, Lairez O, Minville V. Control of spinal anesthesia-induced hypotension in adults. Local Reg Anesth. 2020;13:39–46. doi:10.2147/LRA.S240753. PMID 32581577. PMC7276328.
12. Martyr JW, Clark MX. Hypotension in elderly patients undergoing spinal anaesthesia for repair of fractured neck of femur: a comparison of two different spinal solutions. Anaesth Intensive Care. 2001;29(5):501–505. doi:10.1177/0310057X0102900509. PMID 11669431.
13. Norepinephrine prevents hypotension in older patients under spinal anesthesia with intravenous propofol sedation: a randomized controlled trial. Sci Rep. 2023;13:20977. doi:10.1038/s41598-023-48178-2
14. Wahib M, Mostafa M, Hasanin A, et al. Norepinephrine infusion for prophylaxis against spinal-induced hypotension in elderly patients undergoing hip surgery: a randomized controlled comparison of two doses. BMC Anesthesiol. 2026. ClinicalTrials.gov NCT07077265. A norepinephrine infusion of 0.07 mcg/kg/min was non-inferior to 0.1 mcg/kg/min for maintaining mean arterial pressure, with lower total norepinephrine consumption and fewer heart-rate disturbances.
15. Hemodynamic effects of norepinephrine versus phenylephrine infusion for prophylaxis against spinal anesthesia-induced hypotension in the elderly population undergoing hip fracture surgery: a randomized controlled trial. Korean J Anesthesiol. doi:10.4097/kja.20519
16. Ceruti S, Anselmi L, Minotti B, et al. Prevention of arterial hypotension after spinal anaesthesia using vena cava ultrasound to guide fluid management. Br J Anaesth. 2018;120(1):101–108. doi:10.1016/j.bja.2017.08.001. PMID 29397116.
17. Hyponatremia and transurethral resection of prostate syndrome. OpenAnesthesia. openanesthesia.org/keywords/hyponatermia-and-transurethral-resection-of-prostate-syndrome. Accessed August 2026.
18. TUR syndrome — a report. Urol Case Rep. 2019;26:100982. PMID 31388497, PMC6677916. Reports onset five minutes after the end of the procedure. And: Boukatta B, Sbai H, Messaoudi F, et al. Transurethral resection of prostate syndrome: report of a case. Pan Afr Med J. 2013;14:14. doi:10.11604/pamj.2013.14.14.1906
19. TURP syndrome. Anaesthesia educational review. Anaestheasier, last updated 13 August 2025. anaestheasier.com/turp-syndrome. Describes absorption rate, and shoulder or periumbilical pain as the awake sign of perforation.
20. Porter M, McCormick B. Anaesthesia for transurethral resection of the prostate (TURP). World Federation of Societies of Anaesthesiologists, Update in Anaesthesia. 2003;(16):21–26. resources.wfsahq.org/wp-content/uploads/uia-16-ANAESTHESIA-FOR-TRANSURETHRAL-RESECTION-OF-THE-PROSTATE-TURP.pdf.
21. Transurethral resection of the prostate in saline versus nonconductive solution to treat benign prostatic hyperplasia: a randomized controlled study. UroToday Int J. 2010 Feb;3(1). doi:10.3834/uij.1944-5784.2010.02.05
22. Bipolar transurethral resection in saline: the solution to avoid hyponatraemia and transurethral resection syndrome. PMID 20345336
23. Okuma N, Hino H, Kuroki M, Matsuura T, Mori T. Symptomatic absorption of normal saline during transurethral resection of the prostate: a case report. JA Clin Rep. 2022;8:44. doi:10.1186/s40981-022-00532-5
24. TURP syndrome. Life in the Fast Lane, Critical Care Compendium. litfl.com/turp-syndrome. Summarizing Gravenstein D. Anesth Analg. 1997;84(2):438–446.
25. Spinal anesthesia and hypotensive events in hip fracture surgical repair in elderly patients: a systematic review and meta-analysis. J Anesth Analg Crit Care. 2022;2(1):19. doi:10.1186/s44158-022-00047-6. PMID 37386657. Six randomized trials, 344 patients, median age 82. A low spinal dose, mean 6.5 mg, was associated with a lower incidence of hypotension than a high dose, mean 10.5 mg — odds ratio 0.09 (95% CI 0.04 to 0.21).
26. Nakahira J, Sawai T, Fujiwara A, Minami T. Transurethral resection syndrome in elderly patients: a retrospective observational study. BMC Anesthesiol. 2014;14:30. doi:10.1186/1471-2253-14-30. PMID 24782656. PMC4004457. Men aged 70 and older, monopolar resection with 3% D-sorbitol irrigation under regional anesthesia; 23 of 98 (23.5%, 95% CI 14.9 to 32.0%) met a symptom-based definition.
27. Porto JG, Bhatia AM, Bhat A, et al. Evaluating transurethral resection of the prostate over twenty years: a systematic review and meta-analysis of randomized clinical trials. World J Urol. 2024;42(1):639. doi:10.1007/s00345-024-05332-3. PMID 39547977. PMC11568034. 103 randomized trials, 8,521 patients; pooled TURP syndrome rate 2%.
28. Sieber F, McIsaac DI, Deiner S, et al. 2025 American Society of Anesthesiologists Practice Advisory for Perioperative Care of Older Adults Scheduled for Inpatient Surgery. Anesthesiology. 2025. Found neither neuraxial nor general anesthesia associated with lower delirium risk, including in the hip-fracture subgroup (RR 1.05, 95% CI 0.76–1.43; moderate strength of evidence).
29. Nobuhara C, Devinney M, Berger M. Regional vs general anesthesia and incidence of postoperative delirium in older patients undergoing hip fracture surgery. JAMA. 2022. Notes RAGA was underpowered — the observed delirium rate was less than half the anticipated value.
30. Ben-David B, Frankel R, Arzumonov T, Marchevsky Y, Volpin G. Minidose bupivacaine-fentanyl spinal anesthesia for surgical repair of hip fracture in the aged. Anesthesiology. 2000. 4 mg bupivacaine with 20 mcg fentanyl caused markedly less hypotension than 10 mg (1 of 10 versus 9 of 10 requiring vasopressor).
31. Mafizer M, Kavak Akelma F, Nalbant B. Impact of bupivacaine dose on haemodynamics in elderly hip surgery: a randomized controlled trial. BMC Geriatr. 2026. 5 mg produced better hemodynamic stability and faster discharge than 7.5 mg.
32. Matharu GS, Shah A, Hawley S, et al. The influence of mode of anaesthesia on perioperative outcomes in people with hip fracture: a prospective cohort study from the National Hip Fracture Database for England, Wales and Northern Ireland. BMC Med. 2022. Spinal anesthesia without sedation associated with roughly a 5% absolute reduction in delirium.
33. Tanios AG, Gallagher EL, McManus MS, et al. The effect of type of anaesthetic on delirium after surgery for acute hip fracture: an instrumental variable analysis to assess causation. Anaesth Intensive Care. 2025. Instrumental-variable analysis supporting a delirium reduction with spinal anesthesia when sedation is minimized.
34. Lee JS, Chenkin J, Simard R, et al. Ultrasound-guided regional anesthesia by emergency physicians for hip fractures and delirium: a randomized clinical trial. JAMA Netw Open. 2025. Stepped-wedge trial; ED-delivered ultrasound-guided fascia iliaca blocks reduced 7-day delirium (OR 0.72, 95% CI 0.57–0.93).
35. Jakobsson J, Kalman SH, Lindeberg-Lindvet M, Bartha E. Is postspinal hypotension a sign of impaired cardiac performance in the elderly? An observational mechanistic study. Br J Anaesth. 2017;119(6):1178–1185. doi:10.1093/bja/aex274. PMID 29040402.
36. Olsen F, Hård af Segerstad M, Dalla K, Ricksten SE, Nellgård B. Fractional spinal anesthesia and systemic hemodynamics in frail elderly hip fracture patients. F1000Res. 2023. Attributes the cardiac output fall to venodilation and reduced venous return.
37. Lairez O, Ferré F, Portet N, et al. Cardiovascular effects of low-dose spinal anaesthesia as a function of age: an observational study using echocardiography. Anaesth Crit Care Pain Med. 2015. Advancing age amplifies falls in both cardiac output and systemic vascular resistance.

Sugammadex dosing: 2, 4 and 16 mg/kg

Published at /answers/sugammadex-dosing.

1. Horrow JC, Li W, Blobner M, et al. Actual versus ideal body weight dosing of sugammadex in morbidly obese patients offers faster reversal of rocuronium- or vecuronium-induced deep or moderate neuromuscular block: a randomized clinical trial. BMC Anesthesiol. 2021;21:62. doi:10.1186/s12871-021-01278-w
2. Sugammadex monograph for professionals. Drugs.com. drugs.com/monograph/sugammadex.html. Re-administration wait times, renal impairment guidance, and light-anesthesia signs.
3. Bridion (sugammadex sodium) dosing, indications, interactions and adverse effects. Medscape Reference. reference.medscape.com/drug/bridion-sugammadex-sodium-999851. Coagulation parameter changes at 16 mg/kg, toremifene displacement, renal threshold.
4. Sugammadex titration in cardiac surgery patients. ClinicalTrials.gov NCT05246397. Protocol describing titration in 50 mg increments to a train-of-four ratio of 0.9 or greater.
5. BRIDION (sugammadex) injection: prescribing information. Merck Sharp & Dohme LLC, via DailyMed — the same label as reference 6. dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=5171d883-fe8f-482c-97ab-40b00975b64a. Use of a non-steroidal agent if blockade is needed sooner, with the caveat about delayed depolarizing onset.
6. BRIDION (sugammadex) injection. Merck Sharp & Dohme LLC. US FDA prescribing information, via DailyMed, SPL set ID 5171d883-fe8f-482c-97ab-40b00975b64a; label version published 2 April 2026. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5171d883-fe8f-482c-97ab-40b00975b64a. Source for the 2, 4 and 16 mg/kg indications and depth-of-block criteria; actual body weight dosing; re-administration waiting times; delayed onset/shortened duration of rocuronium 1.2 mg/kg within 30 minutes of reversal; recurrence rate; 7-day non-hormonal contraception advice; progesterone assay interference; coagulation data in the orthopedic thromboprophylaxis trial; severe renal impairment exclusion; and the 0.3% anaphylaxis frequency.
7. Williams R, Bryant H. Sugammadex advice for women of childbearing age. Anaesthesia. 2018;73(1):133–134. doi:10.1111/anae.14176. PMID 29210038. Origin of the modelled 34% reduction in progesterone exposure at 4 mg/kg and the 7-day non-hormonal advice for non-oral contraceptive users.
8. Sugammadex: dosage, mechanism/onset of action, half-life. Medicine.com, reviewed 10 February 2020; drug content from Wolters Kluwer Health, last updated 3 January 2020. medicine.com/drug/sugammadex/hcp. Administration-rate discussion (10-second push per manufacturer; slower push suggested by some authors) and progesterone assay interference.
9. Guidelines for the use of sugammadex and neostigmine/glycopyrrolate. Beth Israel Deaconess Medical Center Department of Anesthesia and Critical Care, guideline ANES CLN 200-007. anesthesia.bidmc.harvard.edu/Policies/Clinical/Clinical/Guidelines/Sugam_Use.pdf. Accessed September 2026. Renal threshold and the case for reversal irrespective of twitch count in patients at risk of respiratory compromise.
10. Safety of sugammadex for the reversal of neuromuscular blockade in ASA class 3 or 4 participants (MK-8616-145). ClinicalTrials.gov NCT03346057. Phase 4 randomized, active-comparator trial in 344 surgical patients; primary endpoints were treatment-emergent sinus bradycardia, sinus tachycardia and other cardiac arrhythmias. Reported no adjudicated anaphylaxis or hypersensitivity reactions.
11. Ji SH, Huh KY, Oh J, et al. Conventional reversal of rocuronium-induced neuromuscular blockade by sugammadex in Korean children: pharmacokinetics, efficacy, and safety analyses. Front Pharmacol. 2023;14:1127932. doi:10.3389/fphar.2023.1127932
12. Hristovska AM, Duch P, Allingstrup M, Afshari A. Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults. Cochrane Database Syst Rev. 2017;8:CD012763 (also published in Anaesthesia. 2018). Source for the pooled composite adverse-event, bradycardia, and residual-paralysis risk ratios across 28 studies (n = 2,298).
13. Devoy T, Hunter M, Smith NA. A prospective observational study of the effects of sugammadex on peri-operative oestrogen and progesterone levels in women who take hormonal contraception. Anaesthesia. 2023. No hormone changes that would threaten contraceptive efficacy.
14. Devoy T, Smith N. Sugammadex and oral contraceptives. Curr Opin Anaesthesiol. 2024. Review; two reported postoperative pregnancies across two large database studies and no trial demonstrating interaction with exogenous contraceptive steroids.
15. Devoy T, Larkin T, Allan M, et al. Sugammadex interference with serum progesterone measurement: an in-vitro study. Anaesthesia. 2026. Apparent progesterone fall is largely an immunoassay interference artifact; no significant change on LC–MS/MS.
16. Gao L, Li B, Shen J, et al. Effect of sugammadex titration versus manufacturer’s recommendation for reversal of rocuronium-induced neuromuscular block: a prospective, randomized, controlled trial. BMC Anesthesiol. 2025. Titration used significantly less drug across all depths of block, with wide interpatient variability.
17. Thilen SR, Weigel WA, Todd MM, et al. 2023 American Society of Anesthesiologists Practice Guidelines for Monitoring and Antagonism of Neuromuscular Blockade. Anesthesiology. 2023. Quantitative monitoring; TOF ratio ≥ 0.9 before extubation; sugammadex favored over neostigmine for deep/moderate rocuronium or vecuronium block.
18. Lee HW, Chen PS, Li MJ, Wong CS. Clinical application of sugammadex in renal impairment: pharmacokinetics and pharmacodynamics. Front Pharmacol. 2026. Reversal quality preserved in severe impairment; extended monitoring advised.

TEE: what it is, and how to manage the anesthetic

Published at /answers/tee-anesthesia-management.

1. American Society of Anesthesiologists and Society of Cardiovascular Anesthesiologists Task Force on Transesophageal Echocardiography. Practice guidelines for perioperative transesophageal echocardiography. Anesthesiology. 2010;112(5):1084–1096. doi:10.1097/ALN.0b013e3181c51e90. PMID 20418689.
2. Samadzadeh Tabrizi N, Gorin AR, Stout PA, et al. Transesophageal echocardiography in patients with esophagectomy: a review. J Cardiothorac Vasc Anesth. 2025;39(1):208–214. doi:10.1053/j.jvca.2023.08.002. PMID 39551697.
3. Hilberath JN, Oakes DA, Shernan SK, Bulwer BE, D’Ambra MN, Eltzschig HK. Safety of transesophageal echocardiography. J Am Soc Echocardiogr. 2010;23(11):1115–1127. doi:10.1016/j.echo.2010.08.013. PMID 20864313. Reviewing the Daniel multicenter series, including fatal hemorrhage where probe insertion disrupted tumor-infiltrated esophageal tissue.
4. Terryn FX, Stangherlin P, Mansvelt B. Zenker’s diverticulum perforation due to transoesophageal echocardiography. Int J Surg Case Rep. 2020. doi:10.1016/j.ijscr.2020.06.016
5. Esophageal perforation with transesophageal echocardiography in an elderly patient with prominent vertebral osteophytes: a case report and review of the literature. CASE (Phila). 2020. PMC7581634. Perforation incidence 0.03–0.09%; osteophytes proposed as relative contraindication.
6. Patel KM, Desai RG, Trivedi K, Neuburger PJ, Krishnan S, Potestio CP. Complications of transesophageal echocardiography: a review of injuries, risk factors, and management. J Cardiothorac Vasc Anesth. 2022;36(8 Pt B):3292–3302. doi:10.1053/j.jvca.2022.02.015. PMID 35317955. Reviewing Cote et al. (11 of 30 perforations diagnosed more than 24 hours after the procedure) and Lennon et al. (both perforations presenting on day 4 and day 11).
7. Chotalia M, Topiwala U, Iqbal A, et al. Incidence of gastrointestinal bleeding after transesophageal echocardiography use in orthotopic liver transplantation. Transpl Int. 2022;35:10753. doi:10.3389/ti.2022.10753
8. Methemoglobinemia due to topical pharyngeal anesthesia during endoscopic procedures. Local Reg Anesth. doi:10.2147/LRA.S12227. Reported benzocaine incidence 0.067–0.45% during TEE.
9. Novaro GM, Aronow HD, Militello MA, et al. Benzocaine-induced methemoglobinemia: experience from a high-volume transesophageal echocardiography laboratory. J Am Soc Echocardiogr. 2003;16(2):170–175. doi:10.1067/mje.2003.5. PMID 12574744. Five cases in 4,336 examinations; incidence 0.115% (95% CI 0.037–0.269).
10. Kane GC, Hoehn SM, Behrenbeck TR, Mulvagh SL. Benzocaine-induced methemoglobinemia based on the Mayo Clinic experience from 28,478 transesophageal echocardiograms: incidence, outcomes, and predisposing factors. Arch Intern Med. 2007;167(18):1977–1982. doi:10.1001/archinte.167.18.1977. PMID 17923598. Nineteen cases over 90 months; incidence 1 per 1,499 (0.067%, 95% CI 0.040–0.100%); mean methemoglobin 32% ± 15%.
11. Easow B, Jiby S, Mathew T, George L, Meek K. Silent hypoxia from benzocaine-induced methemoglobinemia following transesophageal echocardiogram. Cureus. 2025;17(7):e87109. doi:10.7759/cureus.87109. Methemoglobin 31.8% in a patient denying dyspnea.
12. A rare side effect of transesophageal echocardiography: methemoglobinemia from topical benzocaine anesthesia. PMID 17074536. Pulse oximetry 75% against arterial saturation 99%; methemoglobin 69%; resolved with methylene blue 2 mg/kg.
13. Filipiak-Strzecka D, Kasprzak JD, Wiszniewska M, Walusiak-Skorupa J, Lipiec P. The influence of lidocaine topical anesthesia during transesophageal echocardiography on blood methemoglobin level and risk of methemoglobinemia. Int J Cardiovasc Imaging. 2015. doi:10.1007/s10554-015-0608-z. PMID 25663608. No clinically evident cases in 3,354 TEEs. In the prospective arm of 18 patients, mean methemoglobin rose from 0.5 ± 0.1% to 0.6 ± 0.1% at 60 minutes, a rise the authors describe as statistically but not clinically significant (p = 0.02); no patient exceeded the normal range.
14. US Food and Drug Administration. Benzocaine products: risk of methemoglobinemia; standardized warning required on prescription local anesthetics. The announcement is dated 23 May 2018; the FDA page has since been withdrawn, and FDA directs readers to the archived copy: web.archive.org copy of fda.gov.
15. Sainathan S, Andaz S. A systematic review of transesophageal echocardiography-induced esophageal perforation. PMID 23834425. Thirty-five cases from 22 studies; mortality 28.5%; majority occurred in perceived low-risk or smooth examinations.
16. Jougon JB, Gallon P, MacBride T, et al. Esophageal perforation after transesophageal echocardiography. Eur J Cardiothorac Surg. 1999;16(6):686–687. doi:10.1016/S1010-7940(99)00322-X. PMID 10647846. Citing a multicenter study of 10,419 examinations with complication rate 0.18% and mortality 0.0098%.
17. De Luca VM, Cammalleri V, Antonelli G, et al. The other side of the coin: transesophageal echocardiography complications following cardiac surgery and transcatheter structural heart interventions. J Clin Med. 2024;13(15):4291. doi:10.3390/jcm13154291. PMID 39124557. PMC11312835. TEE-related morbidity 0.2–1.2%.
18. Singh A, Nanda C, Mehta Y. Transesophageal echocardiography probe-induced esophageal perforation. J Card Crit Care TSS. 2024;8(3):169–171. doi:10.25259/JCCC_57_2023.
19. Esophageal perforation during transesophageal echocardiography managed conservatively: a case report with a review of the literature on management. Cureus. PMC11695063. Lists dysphagia, hoarseness, lip and dental injury as common, and vocal cord paralysis, arrhythmia, hypotension, seizure and cardiac arrest as serious.
20. Ramalingam G, Choi SW, Agarwal S, et al. Complications related to peri-operative transoesophageal echocardiography — a one-year prospective national audit by the Association of Cardiothoracic Anaesthesia and Critical Care. Anaesthesia. 2020;75(1). doi:10.1111/anae.14734. 22,314 examinations, 17 major complications.
21. Iolascon A, Bianchi P, Andolfo I, et al. Recommendations for diagnosis and treatment of methemoglobinemia. Am J Hematol. 2021;96(12):1666–1678. doi:10.1002/ajh.26340. PMID 34467556. PMC9291883. Usual starting dose of methylene blue 1–2 mg/kg intravenously; methemoglobin should fall significantly in less than an hour.
22. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association. Circulation. 2007;116(15):1736–1754. doi:10.1161/CIRCULATIONAHA.106.183095. PMID 17446442. Antibiotics solely to prevent endocarditis are not recommended for genitourinary or gastrointestinal tract procedures; for dental procedures, prophylaxis is reasonable only in the highest-risk cardiac conditions, for procedures that manipulate gingival tissue or the periapical region of teeth or perforate the oral mucosa.
23. Wilson WR, Gewitz M, Lockhart PB, et al. Prevention of viridans group streptococcal infective endocarditis: a scientific statement from the American Heart Association. Circulation. 2021;143(20):e963–e978. doi:10.1161/CIR.0000000000000969. PMID 33853363. On review of the evidence since 2007, no recommended changes to the 2007 viridans group streptococcal endocarditis prevention guidelines.
24. Wijeysundera DN, Finlayson E. Preoperative evaluation. In: Gropper MA, Eriksson LI, Fleisher LA, et al., eds. Miller’s Anesthesia. 10th ed. Elsevier; 2024:834. Prophylaxis is not required for nondental procedures, transesophageal echocardiography among them, unless there is active infection at the procedure site.
25. Odewole M, Sen A, Okoruwa E, et al. Systematic review with meta-analysis: incidence of variceal hemorrhage in patients with cirrhosis undergoing transesophageal echocardiography. Aliment Pharmacol Ther. 2022. Pooled post-TEE bleeding in cirrhosis under 1%; no significant difference by variceal status; no reported perforations or deaths.
26. Hui RW, Leung CM. Incidence of gastrointestinal bleeding after transesophageal echocardiography in patients with gastroesophageal varices: a systematic review and meta-analysis. J Am Soc Echocardiogr. 2022. Low pooled bleeding rate with no signal of excess risk attributable to varices.
27. Sack JS, Li M, Zucker SD. Bleeding outcomes following transesophageal echocardiography in patients with cirrhosis and esophageal varices. Hepatol Commun. 2021. Multicenter cohort of 191 cirrhotic patients with documented varices; no overt gastrointestinal bleeding after TEE and no benefit from routine pre-procedure endoscopy.
28. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2021;77(4):e25–e197. doi:10.1016/j.jacc.2020.11.018. Transesophageal echocardiography named among nondental procedures for which endocarditis prophylaxis is not recommended even in high-risk patients absent active infection at the site (Class 3: No Benefit).
29. US Food and Drug Administration. Methylene blue injection: prescribing information. Dose 1 mg/kg IV over 5–30 minutes, repeated once at 1 mg/kg if methemoglobin remains above 30% or symptoms persist, maximum two doses; single 1 mg/kg dose in moderate-to-severe renal impairment; lower or greater doses not recommended.
30. Twine AJ, Rees DC. Methaemoglobinaemia: from pathophysiology to contemporary clinical management. Br J Haematol. 2026. Treat symptomatic patients above 20% methemoglobin and asymptomatic patients above 30%; methylene blue ineffective and potentially harmful in G6PD deficiency; cumulative doses above 7 mg/kg cause cyanosis and hemolytic anemia.
31. Hung KC, Wang WT, Yu CH, et al. Efficacy and safety of videolaryngoscopes for transesophageal echocardiography probe insertion: a trial sequential meta-analysis. PLoS One. 2024. Seven randomized trials; videolaryngoscope-guided insertion reduced overall insertion complications (RR 0.28) and hypopharyngeal mucosal trauma versus the conventional technique.
32. Chowdhary S, Bukoye B, Bhansali AM, et al. Risk of topical anesthetic-induced methemoglobinemia: a 10-year retrospective case-control study. JAMA Intern Med. 2013. Thirty-two of 33 topical-anesthetic methemoglobinemia cases occurred in inpatients.

Vasopressor equivalents: why the formulas disagree

Published at /answers/vasopressor-equivalents.

1. Goradia S, Sardaneh AA, Narayan SW, Penm J, Patanwala AE. Vasopressor dose equivalence: a scoping review and suggested formula. J Crit Care. 2021;61:233–240. PMID 33220576. 16,315 articles screened, 21 included.
2. High dose vasopressors: never surrender. PulmCrit / EMCrit. emcrit.org/pulmcrit/high-dose-vasopressor. Discusses the effect of the 2.2:1 versus 10:1 phenylephrine convention on calculated norepinephrine equivalents.
3. Kotani Y, Di Gioia A, Landoni G, Belletti A, Khanna AK. An updated “norepinephrine equivalent” score in intensive care as a marker of shock severity. Crit Care. 2023;27(1):29. doi:10.1186/s13054-023-04322-y. PMID 36670410. Eleven-term formula; dopamine 1/100 and metaraminol 1/8 unchanged from 2021, phenylephrine moves to 0.06, angiotensin II to 0.0025 in ng/kg/min, terlipressin, methylene blue, hydroxocobalamin and midodrine added. Includes the ECMO and inotrope limitation. Erratum in: Crit Care. 2025;29(1):104, which sets the metaraminol factor at 1/8. doi:10.1186/s13054-025-05250-9. PMID 40055820.
4. City of Hope National Medical Center IRB protocol 13384, a phase I trial of IL13Rα2-targeted CAR T cells in recurrent or refractory malignant glioma. ClinicalTrials.gov NCT02208362, study protocol and statistical analysis plan, Amendment V21, protocol dated 08/07/2023. clinicaltrials.gov/study/NCT02208362. Section 16.3.3, within Appendix C on cytokine release syndrome grading, is headed “High-dose vasopressors (all doses are required for > 3 hours)” and carries both the monotherapy thresholds and the VASST equation quoted on this page, including the separate norepinephrine-equivalent bars for vasopressin-containing and non-vasopressin combinations. The protocol names the equation the VASST Trial vasopressor equivalent equation without citing a publication; the trial it refers to is Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358(9):877–887. PMID 18305265.
5. Norepinephrine equivalent dose of vasopressin, phenylephrine and epinephrine in septic shock patients: a prospective study. Sanjay Gandhi Postgraduate Institute of Medical Sciences. ClinicalTrials.gov NCT06499467, registered 12 July 2024. Trial rationale noting that no prospective study has primarily determined the norepinephrine equivalence of the other agents.
6. Mohta M, Dubey M, Malhotra RK, Tyagi A. Comparison of the potency of phenylephrine and norepinephrine bolus doses used to treat post-spinal hypotension during elective caesarean section. Int J Obstet Anesth. 2019;38:25–31. doi:10.1016/j.ijoa.2018.12.002. PMID 30685301. Bolus potency ratio 11.3 (95% CI 8.1–16.9) in 100 consecutive patients.
7. Pölkki A, Pekkarinen PT, Hess B, et al. Noradrenaline dose cutoffs to characterise the severity of cardiovascular failure: data-based development and external validation. Acta Anaesthesiol Scand. 2024;68(10):1400–1408. doi:10.1111/aas.14519. PMID 39210783. Cutoffs of 0.2 and 0.4 mcg/kg/min separating low, intermediate and high cardiovascular failure; hospital mortality 14.0%, 26.4% and 40.2% across bands in the development cohort.
8. Levy B, Fritz C, Tahon E, Jacquot A, Auchet T, Kimmoun A. Vasoplegia treatments: the past, the present, and the future. Crit Care. 2018;22(1):52. PMID 29486781. Notes that “very high dose” thresholds associated with excess mortality range from 0.5 to 2 mcg/kg/min, converging on about 1.
9. Ngan Kee WD. A random-allocation graded dose-response study of norepinephrine and phenylephrine for treating hypotension during spinal anesthesia for cesarean delivery. Anesthesiology. 2017;127(6):934–941. PMID 28872480. Bolus potency ratio 13.1 (95% CI 10.4–15.8); phenylephrine 100 mcg ≈ norepinephrine 8 mcg (95% CI 6–10).
10. Khatoon F, Kocarev M, Fernando R, et al. Optimal infusion rate of norepinephrine for prevention of spinal hypotension for cesarean delivery: a randomized controlled trial, using up-down sequential allocation. Anesth Analg. 2025;141(1):17–25. doi:10.1213/ANE.0000000000007231. PMID 39383097. Infusion-derived potency ratio 12.6 (95% CI 9.92–15.9).
11. Qian J, Zhao YP, Deng JL, et al. Determination of the relative potency of norepinephrine and phenylephrine given as infusions for preventing hypotension during combined spinal-epidural anesthesia for cesarean delivery: a randomized up-and-down sequential allocation study. Front Pharmacol. 2022;13:942005. doi:10.3389/fphar.2022.942005. PMID 35910385. Infusion ED50 norepinephrine 0.061 versus phenylephrine 0.368 mcg/kg/min; relative potency ratio 6.03:1 (95% CI 5.26–6.98).
12. See EJ, Chaba A, Spano S, et al. Exploring the norepinephrine to angiotensin II conversion ratio in patients with vasodilatory hypotension: a post-hoc analysis of the ARAMIS trial. J Crit Care. 2024;79:154453. doi:10.1016/j.jcrc.2023.154453. PMID 37890357. Median norepinephrine-equivalent to angiotensin II conversion ratio 10:1 (5:1 for norepinephrine base) in 37 patients.
13. Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med. 2021;49(11):e1063–e1143. doi:10.1097/CCM.0000000000005337. PMID 34605781. Updated edition: Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2026. Crit Care Med. 2026;54(4):725–812. doi:10.1097/CCM.0000000000007075. PMID 41869847. Norepinephrine first-line, vasopressin second-line and typically added at a norepinephrine equivalent of roughly 0.25–0.5 mcg/kg/min.

Further reading, not cited in the text:

• Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock (2021, updated 2026). Crit Care Med. Norepinephrine first-line, vasopressin second-line.

Video vs direct laryngoscopy: what DEVICE showed

Published at /answers/video-vs-direct-laryngoscopy.

1. Prekker ME, Driver BE, Trent SA, et al; DEVICE Investigators and the Pragmatic Critical Care Research Group. Video versus direct laryngoscopy for tracheal intubation of critically ill adults. N Engl J Med. 2023;389(5):418–429. doi:10.1056/NEJMoa2301601. PMID 37326325. ClinicalTrials.gov NCT05239195. Reports first-attempt success, grade 1 view (76.3% vs 44.7%), severe complications, and the operator-experience subgroup and sensitivity analyses.
2. Critical care alert: video versus direct laryngoscopy for tracheal intubation of critically ill adults — the DEVICE trial. EMRA Critical Care Division, EM Resident, 3 August 2023. emresident.org/critical-care-alert-vl-dl-2023. Secondary summary of the grade 1 view figures and absolute risk reduction.
3. DEVICE trial summary. The Bottom Line. thebottomline.org.uk/summaries/device. Secondary summary of the subgroup analyses and the FELLOW comparison.
4. Xu W, Wang P, Wan J, et al. Comparison of video laryngoscopy and direct laryngoscopy for urgent intubation in newborn infants: a meta-analysis. Paediatr Respir Rev. 2025. Nine RCTs; first-attempt success RR 1.31 (95% CI 1.20–1.44).
5. Lascarrou JB, Boisramé-Helms J, Bailly A, et al; Clinical Research in Intensive Care and Sepsis (CRICS) Group. Video laryngoscopy vs direct laryngoscopy on successful first-pass orotracheal intubation among ICU patients: a randomized clinical trial (MACMAN). JAMA. 2017;317(5):483–493. doi:10.1001/jama.2016.20603. PMID 28118659. First-pass success 67.7% versus 70.3%, p = 0.60. Life-threatening complications, a prespecified secondary outcome: 24/180 (13.3%) with video versus 17/179 (9.5%) with direct, absolute difference 3.8% (95% CI −2.7 to 10.4), p = 0.25. In post hoc analysis, severe life-threatening complications 17/179 (9.5%) versus 5/179 (2.8%), absolute difference 6.7% (95% CI 1.8–11.6), p = 0.01.
6. Hansel J, Rogers AM, Lewis SR, Cook TM, Smith AF. Videolaryngoscopy versus direct laryngoscopy for adults undergoing tracheal intubation. Cochrane Database Syst Rev. 2022;4:CD011136. doi:10.1002/14651858.CD011136.pub3. PMID 35373840. 222 studies, 26,149 participants. For Macintosh-style video laryngoscopes: failed intubation RR 0.41 (95% CI 0.26–0.65, moderate-certainty evidence), successful first attempt RR 1.05 (95% CI 1.02–1.09, low-certainty evidence). Intubator-experience subgroup for failed intubation: experts RR 0.41 (95% CI 0.33–0.50), non-experts RR 0.62 (95% CI 0.32–1.18), no significant subgroup difference. This is an update of the 2016 version of the same review (2016;11:CD011136, PMID 27844477), which searched to February 2015 and found no significant difference in the proportion of successful first attempts.
7. Janz DR, Semler MW, Lentz RJ, et al; Facilitating EndotracheaL intubation by Laryngoscopy technique and apneic Oxygenation Within the ICU (FELLOW) Investigators and the Pragmatic Critical Care Research Group. Randomized trial of video laryngoscopy for endotracheal intubation of critically ill adults. Crit Care Med. 2016;44(11):1980–1987. doi:10.1097/CCM.0000000000001841. PMID 27355526. 150 critically ill adults intubated by pulmonary and critical care fellows in the medical ICU of a single academic center; first-attempt success 68.9% with video (n = 74) versus 65.8% with direct (n = 76), p = 0.68, with better glottic visualization in the video group and no difference in time to intubation, lowest oxygen saturation, complications or in-hospital mortality.
8. Kuitunen I, Räsänen K, Huttunen TT. Video laryngoscopy in neonate and infant intubation — a systematic review and meta-analysis. Eur J Pediatr. 2024. Reports a larger first-attempt-success benefit for video laryngoscopy in the neonatal ICU than in the operating room.
9. Schmid B, Grüßer L, Müller L, et al. Conventional vs video-assisted laryngoscopy for perioperative endotracheal intubations: a randomized clinical trial. JAMA Netw Open. 2026. Perioperative operating-room RCT; first-attempt success 78.2% with direct versus 82.9% with a Macintosh-style video laryngoscope and 87.6% with a hyperangulated video laryngoscope, both video devices superior to direct.
10. DeMasi SC, Casey JD, Semler MW. Evidence-based emergency tracheal intubation. Am J Respir Crit Care Med. 2025. Recommends a video laryngoscope as the primary device for emergency intubation except for training or when it is unavailable.

Further reading, not cited in the text:

• DirEct versus VIdeo LaryngosCopE (DEVICE): protocol and statistical analysis plan. BMJ Open. 2023;13(1):e068978.

What INR is safe for a spinal or epidural?

Published at /answers/what-inr-is-safe-for-a-spinal-or-epidural.

1. Kopp SL, Vandermeulen E, McBane RD, Perlas A, Leffert L, Horlocker T. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (fifth edition). Reg Anesth Pain Med. Published online 29 January 2025. doi:10.1136/rapm-2024-105766. PMID 39880411.
2. Horlocker TT, Vandermeuelen E, Kopp SL, Gogarten W, Leffert LR, Benzon HT. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (fourth edition). Reg Anesth Pain Med. 2018;43(3):263–309. doi:10.1097/AAP.0000000000000763. PMID 29561531. Source of the factor II and X caution and the observation on catheter removal within the first 48 hours of warfarin initiation. It cites the knee replacement series at reference 9 rather than reporting it, and gives the count as more than 12,000, which is the number of arthroplasties.
3. Liu SS, Buvanendran A, Viscusi ER, Hutton E, Lubenow T, Zhou J, Shaw PM, Moric M, Lenart S. Uncomplicated removal of epidural catheters in 4365 patients with international normalized ratio greater than 1.4 during initiation of warfarin therapy. Reg Anesth Pain Med. 2011;36(3):231–235. PMID 21451439.
4. Mulroy MF, Neal JM. Epidural catheter removal in patients on warfarin thromboprophylaxis: a more cautious interpretation of results required? Reg Anesth Pain Med. 2011;36(3):209–210. doi:10.1097/AAP.0b013e3182183583. PMID 21508790.
5. Carvalho B, Mariano ER, Butwick AJ. Epidural catheter removal in patients on warfarin thromboprophylaxis. Reg Anesth Pain Med. 2011. PMID 22024706.
6. Horlocker TT, Heit JA, Wedel DJ, Enneking FK, Rowlingson JC. Safe epidural catheter removal in the patient receiving warfarin: does anybody really know what (prothrombin) time it is? Anesthesiology. 2010;113(3):759–761. doi:10.1097/ALN.0b013e3181ec644a. PMID 20733402.
7. NYSORA. Regional anesthesia in anticoagulated patients. nysora.com/regional-anesthesia/topics/sub-specialties/regional-anesthesia-in-anticoagulated-patients. Source of the reading that the ASRA position on warfarin corresponds to an INR of 1.1 or below, and of vitamin K reversal in the absence of major bleeding. This page also gives 24 hours of neurologic observation after catheter removal, which is the fourth edition’s figure; the fifth edition says at least 48 hours.
8. Kietaibl S, Ferrandis R, Godier A, et al. Regional anaesthesia in patients on antithrombotic drugs: joint ESAIC/ESRA guidelines. Eur J Anaesthesiol. 2022;39(2):100–132. doi:10.1097/EJA.0000000000001600. PMID 34980845. The European counterpart, which the fifth edition ASRA terminology was aligned toward.
9. Parvizi J, Viscusi ER, Frank HG, Sharkey PF, Hozack WJ, Rothman RR. Can epidural anesthesia and warfarin be coadministered? Clin Orthop Relat Res. 2007;456:133–137. doi:10.1097/01.blo.0000246548.25811.2d. PMID 17053565. Retrospective chart review; 11,235 patients, 12,991 knee arthroplasties, warfarin on the day of surgery, catheter removed within 48 hours except in 212 patients. No epidural hematomas on clinical examination. Mean INR at removal 1.54 (range 0.93–4.25) in the 1,030 patients reviewed in detail.
10. Abdel-Wahab OI, Healy B, Dzik WH. Effect of fresh-frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities. Transfusion. 2006;46(8):1279–1285. doi:10.1111/j.1537-2995.2006.00891.x. PMID 16934060. Prospective audit at one hospital; 121 patients transfused for an INR of 1.1–1.85 with a follow-up value within 8 hours.

Which nerve blocks are safe on anticoagulants?

Published at /answers/which-nerve-blocks-are-safe-on-anticoagulants.

1. Kopp SL, Vandermeulen E, McBane RD, Perlas A, Leffert L, Horlocker T. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (fifth edition). Reg Anesth Pain Med. Published online 29 January 2025. doi:10.1136/rapm-2024-105766. PMID 39880411.
2. Horlocker TT, Vandermeuelen E, Kopp SL, Gogarten W, Leffert LR, Benzon HT. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: ASRA Evidence-Based Guidelines (fourth edition). Reg Anesth Pain Med. 2018;43(3):263–309. doi:10.1097/AAP.0000000000000763. PMID 29561531.
3. Horlocker TT, Neal JM, Kopp SL. Practice advisory on the bleeding risks for peripheral nerve and interfascial blockade: going out on a limb. Can J Anaesth. 2019. doi:10.1007/s12630-019-01467-9. Editorial. Source of the deep plexus morbidity statement, the presentation-as-blood-loss point, and the position on holding anticoagulants for analgesic blocks.
4. ESRA newsletter editors. Block and load: the ASRA's regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy, 5th edition. European Society of Regional Anaesthesia, 2025. esraeurope.org/newsletter/article-posts/block-and-load-the-asras-regional-anesthesia-in-the-patient-receiving-antithrombotic-or-thrombolytic-therapy-5th-edition. Summary of the low-dose/high-dose terminology change, the drug-level thresholds, and the alignment with ESAIC/ESRA guidance.
5. Tsui BCH, Kirkham K, Kwofie MK, Tran DQ, Wong P, Chin KJ, Sondekoppam RV. Practice advisory on the bleeding risks for peripheral nerve and interfascial plane blockade: evidence review and expert consensus. Can J Anaesth. 2019;66(11):1356–1384. doi:10.1007/s12630-019-01466-w.
6. Ashken T, West S. Regional anaesthesia in patients at risk of bleeding. BJA Educ. 2021;21(3):84–94. doi:10.1016/j.bjae.2020.11.004. PMID 33664977. PMC7892354. Source of the characterization of the advisory as expert-level opinion and of the fascia iliaca position.
7. Harrop-Griffiths W, Cook T, Gill H, et al. Regional anaesthesia and patients with abnormalities of coagulation: the Association of Anaesthetists of Great Britain & Ireland, the Obstetric Anaesthetists' Association and Regional Anaesthesia UK. Anaesthesia. 2013;68(9):966–972. doi:10.1111/anae.12359. PMID 23905877.
8. Khoo C, Horn JL, Mistry S, Tsui CB. Application of a systematic approach to score bleeding risk in regional anesthesia peripheral nerve block procedures. Abstract, ASRA 44th Annual Regional Anesthesiology and Acute Pain Medicine Meeting, 11–13 April 2019, Las Vegas. Reg Anesth Pain Med. 2019;44:821–836. doi:10.1136/rapm-2019-ASRASpringabs. The published supplement lists abstract titles and authors only, so the survey figures quoted here — fifteen regional anesthesiologists, 94% response — cannot be verified from it. The scoring method itself is published separately: Tsui B. A systematic approach to scoring bleeding risk in regional anesthesia procedures. J Clin Anesth. 2018;49:69–70. doi:10.1016/j.jclinane.2018.06.011.
9. Puncture site bleeding complications of peripheral nerve block in patients taking antithrombotic and anticoagulant drugs: an umbrella review. PMC11108675. Five systematic reviews synthesized qualitatively.
10. Poredoš P. Peripheral nerve blocks in patients on antithrombotic drugs — a rescue or an unnecessary risk? Acta Clin Croat. 2022;61(Suppl 2):67–77. doi:10.20471/acc.2022.61.s2.08. PMID 36824631. PMC9942461. Expert panel consensus classification of peripheral nerve blocks by potential for serious bleeding complications; estimated bleeding incidence 0.67% (95% CI 0.51–0.83).
11. Del Buono R, Padua E, Pascarella G, Costa F, Tognù A, Terranova G, Greco F, Fajardo Perez M, Barbara E. Pericapsular nerve group block: an overview. Minerva Anestesiol. 2021;87(4):458–466. doi:10.23736/S0375-9393.20.14798-9. PMID 33432791. Describes itself as a narrative review. Fifty-seven publications selected, of which 36 were case reports or series and 12 were letters or correspondence; no randomized trial identified. Some cases of femoral and obturator nerve block; no major complication such as hematoma, bleeding or needle-related organ injury reported.
12. Pericapsular Nerve Group Block. StatPearls. NCBI Bookshelf NBK567757.
13. Pascarella G, Costa F, Gargano F, et al. Pericapsular nerve group block in patients on antithrombotic drugs: a reply to ESAIC/ESRA guidelines. Correspondence. Eur J Anaesthesiol. 2023;40(6):454–455. doi:10.1097/EJA.0000000000001800. PMID 36924169.
14. Darmanis S, Lewis A, Mansoor A, Bircher M. Corona mortis: an anatomical study with clinical implications in approaches to the pelvis and acetabulum. Clin Anat. 2007;20(4):433–439. PMID 16944498. Forty cadavers, 80 hemipelvises; anastomosis in 83%, of which 60% exceeded 3 mm diameter; located 40–96 mm from the symphysis pubis.
15. Corona mortis. Radiopaedia reference article. radiopaedia.org/articles/corona-mortis. Pooled prevalence across hemipelvises: venous 41.7%, arterial 17%, combined 49.3%.
16. Tsui BCH, Kirkham K, Kwofie MK, et al. Practice advisory on the bleeding risks for peripheral nerve and interfascial blockade: rooted in evidence. Can J Anaesth. 2019. doi:10.1007/s12630-019-01520-7. Authors' reply to the editorial.
17. Kietaibl S, Ferrandis R, Godier A, et al. Regional anaesthesia in patients on antithrombotic drugs: joint ESAIC/ESRA guidelines. Eur J Anaesthesiol. 2022;39(2):100–132. doi:10.1097/EJA.0000000000001600. PMID 34980845. Notes that hold intervals do not apply to peripheral nerve blocks with low bleeding risk that are superficial and compressible.
18. Girón-Arango L, Peng PWH, Chin KJ, Brull R, Perlas A. Pericapsular nerve group (PENG) block for hip fracture. Reg Anesth Pain Med. 2018;43(8):859–863. doi:10.1097/AAP.0000000000000847. PMID 30063657. The original description of the technique, presented as a novel ultrasound-guided approach and reported in 5 consecutive patients.

Why oxygenation fails on one lung

Published at /answers/why-oxygenation-fails-on-one-lung.

1. Archer S, Michelakis E. The mechanism(s) of hypoxic pulmonary vasoconstriction: potassium channels, redox O₂ sensors, and controversies. News Physiol Sci. 2002. doi:10.1152/nips.01388.2002
2. Dunham-Snary KJ, Wu D, Sykes EA, Thakrar A, Parlow LRG, Mewburn JD, Parlow JL, Archer SL. Hypoxic pulmonary vasoconstriction: from molecular mechanisms to medicine. Chest. 2017;151(1):181–192. doi:10.1016/j.chest.2016.09.001. PMID 27645688
3. Archer SL, Dunham-Snary KJ, Bentley RET, Alizadeh E, Weir EK. Hypoxic pulmonary vasoconstriction: an important component of the homeostatic oxygen sensing system. Physiol Res. 2024;73(S2):S493–S510. doi:10.33549/physiolres.935431. PMID 39589299
4. Shum S, et al. Hypoxaemia during one lung ventilation. BJA Educ. 2023;23(9):328–336. doi:10.1016/j.bjae.2023.05.006. Source of the threshold alveolar oxygen tension (PAO₂) of 85–90 mmHg with maximum response at 65–70 mmHg, the cardiac output and mixed venous saturation relationship, the effects of anesthetic drugs on the response, and the share of cardiac output reaching each lung in the lateral position.
5. Petersson J, Glenny RW. Gas exchange and ventilation–perfusion relationships in the lung. Eur Respir J. 2014;44(4):1023–1041. PMID 25063240
6. Raimondi Cominesi D, et al. Pulmonary shunt in critical care: a practical approach with clinical scenarios. J Anesth Analg Crit Care. 2024. doi:10.1186/s44158-024-00147-5
7. Lee K, et al. Effects of iloprost on oxygenation during one-lung ventilation in patients with low diffusing capacity for carbon monoxide: a randomized controlled study. J Clin Med. 2022;11(6). PMID 35329869. Source of the 5–10% incidence of hypoxemia.
8. Slinger P, Campos JH. Physiology of the lateral decubitus position, open chest and one-lung ventilation. In: Principles and Practice of Anesthesia for Thoracic Surgery. Figures modified from Benumof, Elsevier 1995. Edition and page not yet confirmed.
9. Li X, et al. The effects of thoracic epidural analgesia on oxygenation and pulmonary shunt fraction during one-lung ventilation: a meta-analysis. BMC Anesthesiol. 2015. doi:10.1186/s12871-015-0142-5
10. Hedenstierna G, Edmark L. Mechanisms of atelectasis in the perioperative period. Best Pract Res Clin Anaesthesiol. 2010;24(2):157–169. PMID 20608554. Source of the 90% incidence, the collapse of up to 15–20% of the lung at the bases before surgery, and the critical ventilation–perfusion values.
11. Effects of anesthesia on the respiratory system. OpenAnesthesia. openanesthesia.org/keywords/effects-of-anesthesia-on-the-respiratory-system. Source of the 0.8–1.0 L fall in FRC from upright to supine; corroborates the induction figure, the 90% incidence and the three atelectasis mechanisms; no stable identifier or version.
12. Aretha D, et al. Safety and effectiveness of alveolar recruitment maneuvers and positive end-expiratory pressure during general anesthesia for cesarean section: a prospective, randomized trial. Int J Obstet Anesth. 2017;30:30–38. PMID 28108076
13. Gianni S, Vaporidi K, Cereda M, Berra L. Respiratory physiology and pathophysiology. In: Gropper MA, Eriksson LI, Fleisher LA, et al., eds. Miller’s Anesthesia. 10th ed. Elsevier; 2024:255. Source of diaphragm elevation by abdominal contents as the cause of the fall in FRC on lying supine.

Why regional blood flow fails

Published at /answers/why-regional-blood-flow-fails.

1. Gelman S. Venous function and central venous pressure: a physiologic story. Anesthesiology. 2008;108(4):735–748. PMID 18362606
2. Greenway CV, Lister GE. Capacitance effects and blood reservoir function in the splanchnic vascular bed during non-hypotensive haemorrhage and blood volume expansion in anaesthetized cats. J Physiol. 1974;237(2):279–294. PMID 4825450
3. Greenway CV. Role of splanchnic venous system in overall cardiovascular homeostasis. Fed Proc. 1983;42(6):1678–1684. PMID 6832386
4. Lankadeva YR, et al. Role of perioperative hypotension in postoperative acute kidney injury: a narrative review. Br J Anaesth. 2022;128(6):931–948. PMID 35465952. Source of the renal versus cerebral autoregulatory limit, the factors blunting renal autoregulation, the bypass effect, and urinary oxygen tension as a medullary proxy.
5. Li S, et al. Pathological triad of perioperative acute kidney injury: renal microcirculatory hypoxia, mitochondrial damage, and immuno-metabolic reprogramming. Front Immunol. 2026;17:1843391. PMID 42338604
6. Brezis M, Rosen S, Epstein F. The pathophysiologic implications of medullary hypoxia. Am J Kidney Dis. 1989;13(3):253–258. doi:10.1016/S0272-6386(89)80062-9. PMID 2493191.
7. Franzén S, et al. Anesthesia and the renal sympathetic nervous system in perioperative acute kidney injury. Semin Nephrol. 2022. doi:10.1016/j.semnephrol.2022.10.009. Source of the baroreceptor and renin–angiotensin–aldosterone compensation point.
8. Lautt WW. Mechanism and role of intrinsic regulation of hepatic arterial blood flow: hepatic arterial buffer response. Am J Physiol. 1985;249(5 Pt 1):G549–G556. doi:10.1152/ajpgi.1985.249.5.G549. PMID 3904482.
9. Eipel C, Abshagen K, Vollmar B. Regulation of hepatic blood flow: the hepatic arterial buffer response revisited. World J Gastroenterol. 2010;16(48):6046–6057. PMID 21182219
10. Lautt WW. Resistance in the hepatic artery. In: Hepatic Circulation: Physiology and Pathophysiology. Morgan & Claypool Life Sciences; 2009. NCBI Bookshelf NBK53066. Source of the space of Mall description and the washout mechanism.
11. Lautt WW. Regulatory processes interacting to maintain hepatic blood flow constancy: vascular compliance, hepatic arterial buffer response, hepatorenal reflex, liver regeneration, escape from vasoconstriction. Hepatol Res. 2007;37(11):891–903. doi:10.1111/j.1872-034X.2007.00148.x. PMID 17854463. Source of the passive volume expulsion and the 50% passive volume expulsion.
12. Lautt WW, Legare DJ, d’Almeida MS. Adenosine as putative regulator of hepatic arterial flow (the buffer response). Am J Physiol. 1985;248(3 Pt 2):H331–H338. PMID 2579585. Buffering of 25.5 ± 2.7% of the decrease in portal flow after superior mesenteric artery occlusion in anesthetized cats.
13. Lautt WW, Legare DJ, Ezzat WR. Quantitation of the hepatic arterial buffer response to graded changes in portal blood flow. Gastroenterology. 1990;98(4):1024–1028. PMID 2311859. Hepatic arterial flow changes inversely with portal flow in both directions: nearly full dilation at low portal flows, shown by inability to dilate further to adenosine, and nearly full constriction at high portal flows, shown by lack of further constriction to norepinephrine. With arterial pressure uncontrolled, active and passive effects combined reach 44% ± 4% over the full range of portal flows.
14. Ahmed MF, Kamel I. Supine hypotensive syndrome. In: Abd-Elsayed A, ed. Advanced Anesthesia Review. Oxford University Press; 2023. Chapter 311, pp. 787–788. ISBN 9780197584521. doi:10.1093/med/9780197584521.003.0310. Source of the 15–30 mmHg and 20 beats/min definition, the 18–20 week onset, the 10–15% incidence, the 30% and 20% flow reductions, and the collateral routes.
15. Kacmar RM, Gaiser R. Physiologic changes of pregnancy. In: Chestnut DH, ed. Chestnut’s Obstetric Anesthesia: Principles and Practice. 6th ed. Elsevier; 2020:13–37. The source the chapter above rests its own definition and onset figures on.
16. Soranno DE, Coopersmith CM, Brinkworth JF, et al. A review of gut failure as a cause and consequence of critical illness. Crit Care. 2025;29(1):91. doi:10.1186/s13054-025-05309-7. PMID 40011975. Source of the 25–30% share of resting cardiac output and of the celiac, superior mesenteric and inferior mesenteric supply.
17. Aoki T, Imamura H, Kaneko J, et al. Intraoperative direct measurement of hepatic arterial buffer response in patients with or without cirrhosis. Liver Transpl. 2005;11(6):684–691. doi:10.1002/lt.20380. PMID 15915492. Hepatic arterial and portal flow measured during surgery in 39 patients with cirrhosis and 22 without: in cirrhosis the buffer response was already activated at baseline, and the acute response to portal vein clamping was blunted.

Why the circulation fails under anesthesia

Published at /answers/why-the-circulation-fails-under-anesthesia.

1. Varma PK, et al. Perioperative right ventricular function and dysfunction in adult cardiac surgery, part 1: anatomy, pathophysiology and diagnosis. Indian J Thorac Cardiovasc Surg. 2022;38(1):45–57. PMID 34898875
2. He Q, et al. Clinical usefulness of right ventricle–pulmonary artery coupling in cardiovascular disease. J Clin Med. 2023;12(7). PMID 37048609
3. Haddad F, Couture P, Tousignant C, Denault AY. The right ventricle in cardiac surgery, a perioperative perspective: I. Anatomy, physiology, and assessment. Anesth Analg. 2009;108(2):407–421. PMID 19151264
4. Levy D, et al. Post-operative right ventricular failure after cardiac surgery: a cohort study. Front Cardiovasc Med. 2021;8:667328. PMID 34195233. Source of the 2.9% incidence in 3,826 patients.
5. Varma PK, et al. Perioperative right ventricular function and dysfunction in adult cardiac surgery, part 2: management of right ventricular failure. Indian J Thorac Cardiovasc Surg. 2022;38(2):157–166. PMID 34751203
6. Boyette LC, Manna B. Physiology, myocardial oxygen demand. StatPearls, NCBI Bookshelf NBK499897. PMID 29763072.
7. Duncker DJ, Koller A, Merkus D, Canty JM Jr. Regulation of coronary blood flow in health and ischemic heart disease. Prog Cardiovasc Dis. 2014;57(5):409–422. PMID 25475073. Source of the 40 versus 25 mmHg transmural autoregulation limits.
8. Duncker DJ, Bache RJ. Regulation of coronary blood flow during exercise. Physiol Rev. 2008. doi:10.1152/physrev.00045.2006
9. Hoffman JIE, Buckberg GD. The myocardial oxygen supply:demand index revisited. J Am Heart Assoc. 2014;3(1):e000285. doi:10.1161/JAHA.113.000285. PMID 24449802
10. Heward SJ, Shams P, Widrich J. Coronary perfusion pressure. StatPearls, NCBI Bookshelf NBK551531
11. Guyton AC. Determination of cardiac output by equating venous return curves with cardiac response curves. Physiol Rev. 1955;35(1):123–129. PMID 14356924
12. Gelman S. Venous function and central venous pressure: a physiologic story. Anesthesiology. 2008;108(4):735–748. PMID 18362606
13. Ltaief Z, et al. Vasoplegic syndrome after cardiopulmonary bypass in cardiovascular surgery: pathophysiology and management in critical care. J Clin Med. 2022;11(21). PMID 36362635
14. Muhammad R, Dharmadjati BB, Mulia EPB, Rachmi DA. Vasoplegia: mechanism and management following cardiopulmonary bypass. Eurasian J Med. 2022;54(1):92–99. doi:10.5152/eurasianjmed.2022.20394. PMID 35307639
15. Barnes TJ, Hockstein MA, Jabaley CS. Vasoplegia after cardiopulmonary bypass: a narrative review of pathophysiology and emerging targeted therapies. SAGE Open Med. 2020. doi:10.1177/2050312120935466
16. Busse LW, et al. Vasoplegic syndrome following cardiothoracic surgery: review of pathophysiology and update of treatment options. Crit Care. 2020. doi:10.1186/s13054-020-2743-8
17. Torrez JP, et al. Vasoplegic syndrome following bypass: a comprehensive review of pathophysiology and proposed treatments. Cureus. 2025;17(1):e78057. PMID 40013224

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