A Double-Blind, Placebo-Controlled Trial of Four Fixed Rate Infusion Regimens of Phenylephrine for Hemodynamic Support During Spinal Anesthesia for Cesarean Delivery

• DOI: 10.1213/ane.0b013e3181e1db21
• Publication Date: 2010-05-22T08:22:30Z
• Authors: Terrence K. Allen; Ronald B. George; William D. White; Holly A. Muir; Ashraf S. Habib
• Keywords: Dose-Response Relationship, Drug; Cesarean Section; Blood Pressure; Kaplan-Meier Estimate; Carbon Dioxide; Fetal Blood; Placebo Effect; Anesthesia, Spinal; Drug Administration Schedule; 3. Good health; Oxygen; Phenylephrine; 03 medical and health sciences; 0302 clinical medicine; Double-Blind Method; Elective Surgical Procedures; Pregnancy; Antiemetics; Humans; Female; Infusions, Parenteral; Hypotension; Adrenergic alpha-Agonists

The administration of prophylactic phenylephrine infusions in combination with fluid cohydration significantly reduces the incidence of hypotension in women having cesarean delivery under spinal anesthesia. The ideal dosing regimen for this purpose is not known. In this study, we investigated the dose of phenylephrine that, when administered as a prophylactic fixed rate infusion, is associated with the least interventions needed to maintain maternal systolic blood pressure (SBP) within 20% of baseline.Women undergoing elective cesarean delivery were randomly allocated to receive placebo or prophylactic phenylephrine infusion at 25, 50, 75, or 100 μg/min immediately after spinal anesthesia in combination with a 2-L fluid coload. Maternal SBP was maintained within the target range using a predetermined algorithm. The number of physician interventions, hemodynamic performance, intraoperative nausea and vomiting, and umbilical cord blood gases were compared among the groups.One hundred one patients were included in the analysis. There were no differences between the placebo and phenylephrine groups in the number of interventions needed to maintain maternal SBP within the target range. Doses of phenylephrine of 25 and 50 μg/min were associated with significantly fewer interventions when compared with 100 μg/min (P = 0.004 vs 50 μg/min, P = 0.02 vs 25 μg/min). Predelivery hypotension was more frequent in the control group compared with all phenylephrine groups. Phenylephrine 75 and 100 μg/min groups were associated with a significantly higher incidence of predelivery hypertension compared with control (P < 0.001 vs 75 μg/min and 100 μg/min). There was a trend toward an increase in median magnitude of deviations of SBP above or below baseline (P = 0.006), and the bias of SBP to be above baseline (P < 0.001) with increasing rates of phenylephrine infusion. There were no differences in the incidence and severity of intraoperative nausea and vomiting and umbilical cord blood gases among the groups.The use of prophylactic fixed rate phenylephrine infusions did not significantly reduce the number of physician interventions needed to maintain maternal predelivery SBP within 20% of baseline compared with placebo. However, prophylactic phenylephrine infusions reduced the incidence and severity of maternal predelivery hypotension. Phenylephrine 25 and 50 μg/min administered as a prophylactic fixed rate infusion provided greater maternal hemodynamic stability than phenylephrine 75 and 100 μg/min. Prophylactic fixed rate infusions may have limited application in clinical practice, and future studies assessing the accuracy of hemodynamic control with variable rate phenylephrine infusions are needed.