Allen 2010.

Study characteristics
Methods	RCT
Participants	109 women Inclusion criteria: ASA physical status I and II pregnant women scheduled for elective caesarean delivery under spinal anaesthesia; singleton gestation at a gestational age of > 36 weeks Exclusion criteria: women who were in labour, BMI > 45 kg/m², type 1 diabetes mellitus, hypertensive disease, cardiac disease, a fetus with severe congenital anomalies, history of monoamine oxidase inhibitor use, or those who were included in any other anaesthesia drug studies Setting: USA
Interventions	Phenylephrine dosage variations versus placebo Group 1: phenylephrine infusion 25 μg/min Group 2: phenylephrine infusion 50 μg/min Group 3: phenylephrine infusion 75 μg/min Group 4: phenylephrine infusion 100 μg/min Group 5: placebo (normal saline 50 mL) infusion All infusions were commenced immediately after spinal injection, at 60 mL/h in combination with a standardised fluid coload.  The study drug was infused until 10 min after delivery, after which the study ended and further management was at the discretion of the anaesthesiologist. All women received a standardised aspiration prophylaxis, a standardised spinal anaesthetic technique and dose, and a standardised oxytocin bolus and subsequent infusion after delivery. Hypotension (requiring intervention) was treated by administering a 100 μg bolus of phenylephrine. Hypertension treatment: treated by stopping the infusion. Infusions were only restarted when the SBP decreased to below the upper limit of the target range above baseline). NOTE: if the study drug infusion had to be stopped on 3 occasions, then it was stopped permanently, and BP was maintained with phenylephrine boluses for the remainder of the study. Bradycardia treatment: administration of glycopyrrolate 0.4 mg
Outcomes	Maternal: hypotension, pre and postdelivery birth; hypotension requiring intervention; nausea and vomiting; cardiac dysrhythmia; pre and postbirth reactive hypertension; bradycardia Neonatal: acidosis (cord or neonatal bloods with pH < 7.2); neonatal Apgar score < 8 at 5 min
Notes	Hypotension defined as SBP < 20% below baseline Hypotension requiring intervention defined as SBP decrease > 20% baseline or < 90 mmHg Hypertension defined as SBP > 20% above baseline Bradycardia defined as < 50 bpm
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation in blocks of 20
Allocation concealment (selection bias)	Unclear risk	Each study syringe was identified by a study number.  The infusions were prepared in identical 50 mL syringes by a physician not involved in the study.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Double blind".  To maintain blinding, the infusions were prepared in identical 50 mL syringes containing normal saline for the placebo, or the appropriate concentrations of phenylephrine (25 μg, 50 μg, 75 μg, or 100 μg) for the drug interventions. A physician not involved in the study coded and prepared the syringes.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not stated who was responsible for recording of outcomes, and whether they were blinded to the allocated intervention
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	8/109 patients excluded (not specified which groups they were from), due to inadequate or failed spinal anaesthesia. Insufficient samples were obtained for umbilical cord blood gases for some babies because of insufficient samples, clotted samples or sampling errors: 1 (placebo group); 2 (phenylephrine 25 μg group); 2 (phenylephrine 50 μg group) and 5 (phenylephrine 100 μg group).
Selective reporting (reporting bias)	Low risk	Most expected outcomes reported
Other bias	Low risk	No apparent sources of other bias Study funded by Duke University Medical Center Department of Anesthesiology, Division of Women's Anesthesia