A Random-allocation Graded Dose–Response Study of Norepinephrine and Phenylephrine for Treating Hypotension during Spinal Anesthesia for Cesarean Delivery

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Background:Norepinephrine has been investigated as a potential alterative to phenylephrine for maintaining blood pressure during spinal anesthesia for cesarean delivery with the advantage of less depression of maternal heart rate and cardiac output. However, the relative potencies of these two vasopressors have not been fully determined in this context.Methods:In a random-allocation, graded dose–response study, 180 healthy patients undergoing spinal anesthesia for elective cesarean delivery received a single bolus of norepinephrine in one of six different doses ranging from 4 to 12 µg or phenylephrine in one of six different doses ranging from 60 to 200 µg to treat the first episode of hypotension. The magnitude of response was measured as the percentage of full restoration of systolic blood pressure to the baseline value. Dose–response analysis was performed using nonlinear regression to derive four-parameter logistic dose–response curves, which were compared to determine relative potency.Results:Data were analyzed for 180 patients. The estimated ED50 values (dose giving a 50% response) were norepinephrine 10 µg (95% CI, 6 to 17 µg) and phenylephrine 137 µg (95% CI, 79 to 236 µg). The estimated relative potency ratio for the two drugs was 13.1 µg (95% CI, 10.4 to 15.8 µg).Conclusions:Comparative dose–response analysis was completed for norepinephrine and phenylephrine given as a bolus to treat the first episode of hypotension in patients undergoing spinal anesthesia for cesarean delivery. The estimated dose equivalent to phenylephrine 100 µg was norepinephrine 8 µg (95% CI, 6 to 10 µg). These results may be useful to inform the design of future comparative studies.

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