title: A double-blind, placebo-controlled trial of four fixed rate infusion regimens of phenylephrine for hemodynamic support during spinal anesthesia for cesarean delivery.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA. terrence.allen@duke.edu
authors.forename: Terrence K
authors.initials: TK
authors.lastname: Allen
authors.forename: Ronald B
authors.initials: RB
authors.lastname: George
authors.forename: William D
authors.initials: WD
authors.lastname: White
authors.forename: Holly A
authors.initials: HA
authors.lastname: Muir
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Habib
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage*; D000775:Anesthesia, Spinal / Q000009:adverse effects; D000932:Antiemetics / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D002245:Carbon Dioxide / Q000097:blood; D002585:Cesarean Section / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017558:Elective Surgical Procedures; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D006801:Humans; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D007263:Infusions, Parenteral; D053208:Kaplan-Meier Estimate; D010100:Oxygen / Q000097:blood; D010656:Phenylephrine / Q000008:administration & dosage*; D015990:Placebo Effect; D011247:Pregnancy; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000316:Adrenergic alpha-Agonists; D000932:Antiemetics; D002245:Carbon Dioxide; D010656:Phenylephrine; D010100:Oxygen