ED95 of phenylephrine to prevent spinal-induced hypotension and/or nausea at elective cesarean delivery.
BACKGROUND
The purpose of this trial was to determine the 95% effective dose (ED95) of phenylephrine by intermittent i.v. bolus, to prevent spinal-induced hypotension and/or nausea at elective cesarean delivery.


METHODS
The study was conducted in a double-blinded fashion in 50 patients undergoing elective cesarean delivery under spinal anesthesia. The dose of phenylephrine was determined using up-down sequential allocation, modified by a variation of the Narayana rule. Systolic pressure and heart rate were assessed every minute until uterine incision. The first patient was assigned a 40-microg dose, and the dose to subsequent patients varied by 10-microg increments or decrements. An adequate response was defined as absence of hypotension (systolic pressure <80% of baseline) and nausea. The study solution was given immediately after spinal administration, without prior pressure measurement, and thereafter when the systolic pressure was <or=control values. fell below baseline. The ED95 was determined by a logistic model with non-log-transformed doses, using Firth's penalized maximum likelihood method with 95% confidence intervals based on penalized profile likelihood.


RESULTS
The ED95 of phenylephrine was estimated as 159 microg (95% confidence interval: 122-371 microg), although the largest dose given in the study was only 120 microg. Hypertension (systolic blood pressure >120% of baseline) was observed in 14 cases, immediately after intrathecal injection and prophylactic phenylephrine administration in all cases.


CONCLUSIONS
The ED95 of phenylephrine, administered as intermittent boluses to prevent pre-delivery spinal-induced hypotension and/or nausea at elective cesarean delivery, is at least 122 microg (lower limit of the confidence interval). The safety of this dose warrants further studies.
Tanaka
M
M
Department of Anesthesia and Pain Management, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Balki
M
M
Parkes
R K
RK
Carvalho
J C A
JC
D000328:Adult; D000773:Anesthesia, Obstetrical / Q000009:adverse effects*; D000775:Anesthesia, Spinal / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D002585:Cesarean Section; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control*; D007231:Infant, Newborn; D007275:Injections, Intravenous; D009325:Nausea / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control*; D010656:Phenylephrine / Q000008:administration & dosage* / Q000627:therapeutic use*; D011247:Pregnancy; D011256:Pregnancy Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D014839:Vomiting / Q000453:epidemiology / Q000517:prevention & control; D055815:Young Adult
D014662:Vasoconstrictor Agents; D010656:Phenylephrine