Does ondansetron prevent spinal hypotension?

Partly, and by a mechanism worth understanding. Ondansetron blunts the Bezold–Jarisch reflex, which is one contributor to the hypotension and bradycardia that follow a spinal — not the main one. It reduces the incidence of both and lowers vasopressor requirement. It does not replace a vasopressor, and it is not a reason to give less attention to either.

The mechanism

A spinal block produces sympathectomy, and the venodilation that follows drops preload. In a ventricle that is suddenly underfilled but still contracting vigorously, 5-HT₃ receptors on intracardiac vagal afferents are stimulated, and the reflex response is the wrong one for the situation: bradycardia and further vasodilation rather than the tachycardia you would expect from hypovolemia. That is the Bezold–Jarisch reflex, and it is why a patient can become bradycardic while becoming hypotensive after a spinal.

Ondansetron is a 5-HT₃ antagonist. Given before the block, it occupies the receptor the reflex runs through. This is a mechanistic rationale that predicts a partial effect, and a partial effect is what the trials show — the primary cause of the hypotension is still the sympathectomy, and nothing about a 5-HT₃ antagonist touches that.

What the trials show

The largest synthesis is a systematic review and meta-analysis of thirteen randomized controlled trials in 1,225 subjects, published in the AANA Journal:

The bradycardia effect being the larger of the two is exactly what the mechanism predicts, and it is the most useful thing in the result: the reflex arc ondansetron blocks is more responsible for the heart rate than for the pressure.

What this does not mean

It is not a substitute for a vasopressor. A risk ratio of 0.64 is a reduction in incidence, not prevention. The prophylactic phenylephrine infusion, the fluid co-load and the left uterine displacement all still do the work they did before; ondansetron sits alongside them.

The trials are heterogeneous. Doses studied cluster at 4 mg and 8 mg given a few minutes before the block, but timing, spinal dose, vasopressor regimen and the definition of hypotension all vary between studies. That is the usual reason a plausible intervention has a confidence interval this wide.

Most patients are getting it anyway. In cesarean delivery the same dose is commonly given for nausea and vomiting prophylaxis, which makes the hemodynamic effect a reasonable secondary consideration in timing rather than a new drug to add.