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Background: Norepinephrine is an effective vasopressor during spinal anaesthesia for Caesarean delivery. However, before it can be fully recommended, possible adverse effects on neonatal outcome should be excluded. We aimed to test the hypothesis that umbilical arterial cord pH is at least as good (non-inferior) when norepinephrine is used compared with phenylephrine for treatment of hypotension., Methods: We enrolled 668 subjects having elective and non-elective Caesarean delivery under spinal or combined spinal-epidural anaesthesia in this randomised, double-blind, two-arm parallel, non-inferiority clinical trial. Arterial blood pressure was maintained using norepinephrine 6 μg ml -1 or phenylephrine 100 μg ml -1 according to the practice of the anaesthetist, either prophylactically or therapeutically, as an infusion or bolus. The primary outcome was umbilical arterial pH with a chosen non-inferiority margin of 0.01 units., Results: Of 664 subjects (531 elective and 133 non-elective) who completed the study, umbilical arterial cord blood was analysed for 351 samples from 332 subjects in the norepinephrine group and 343 samples from 332 subjects in the phenylephrine group. Umbilical arterial pH was non-inferior in the norepinephrine group (mean, 7.289; 95% confidence interval [CI], 7.284-7.294) compared with the phenylephrine group (mean, 7.287; 95% CI, 7.281-7.292) (mean difference between groups, 0.002; 95% CI, -0.005 to 0.009; P=0.017). Subgroup analysis confirmed the non-inferiority of norepinephrine for elective cases but was inconclusive for non-elective cases., Conclusions: Norepinephrine was non-inferior to phenylephrine for neonatal outcome assessed by umbilical arterial pH. These results provide high-quality evidence supporting the fetal safety of norepinephrine in obstetric anaesthesia., Clinical Trial Registration: ChiCTR-IPR-15006235., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Ondansetron has been shown to reduce the incidence of hypotension and vasopressor requirement during spinal anesthesia for obstetric and nonobstetric surgery. However, the magnitude of this effect has not been fully quantified. In this parallel-group, randomized, double-blinded study, we determined the effective dose in 50% of subjects (ED50) of a prophylactic phenylephrine infusion for preventing hypotension in patients who received a single dose of intravenous ondansetron 4 mg or saline control before combined spinal-epidural anesthesia for elective cesarean delivery. ED50 values obtained were compared to estimate the effect of ondansetron versus placebo on vasopressor requirement., Methods: Sixty parturients were randomly assigned to receive ondansetron (group O) or saline control (group C) 10 minutes before positioning for induction of spinal anesthesia. A prophylactic phenylephrine infusion was used to prevent hypotension. The first patient in each group received a phenylephrine infusion at the rate of 0.5 µg/kg/min. The infusion rate for each subsequent patient was varied with increments or decrements of 0.05 µg/kg/min based on the response of the previous patient, and the effective dose of the phenylephrine infusion for preventing hypotension in 50% of patients (ED50) was calculated for each group and compared using up-down sequential analysis. Probit regression was applied as a backup and sensitivity analysis was used to compare ED50 values for phenylephrine between groups by comparing calculated relative mean potency., Results: The ED50 (mean [95% confidence interval (CI)]) of the rate of phenylephrine infusion was lower in group O (0.24 µg/kg/min [0.10-0.38 µg/kg/min]) compared with group C (0.32 µg/kg/min [0.14-0.47 µg/kg/min]) (P < .001). The total consumption of phenylephrine (mean ± standard deviation [SD]) until delivery was lower in group O (316.5 ± 25.9 µg) than in group C (387.7 ± 14.7 µg, P = .02). The estimate of relative median potency for phenylephrine for group O versus group C was 0.74 (95% CI, 0.37-0.95)., Conclusions: Under the conditions of this study, intravenous ondansetron 4 mg reduced the ED50 of a prophylactic phenylephrine infusion by approximately 26% in patients undergoing cesarean delivery under combined spinal-epidural anesthesia.

Background: Prophylactic IV infusion of phenylephrine has been recommended to prevent hypotension during spinal anesthesia for cesarean delivery. However, the optimal infusion dose is unknown. This study aimed to determine the infusion dose of phenylephrine that would be effective in preventing hypotension in 50% (ED50) and 90% (ED90) of patients when administered as a prophylactic infusion at a fixed rate based on the individual body weight., Methods: Eighty parturients scheduled for elective cesarean delivery were randomly allocated to receive IV infusion of prophylactic phenylephrine at 0.25, 0.375, 0.5, or 0.625 µg/kg/min (n = 20 per group) started immediately after intrathecal injection of 10 mg hyperbaric bupivacaine and 5 µg sufentanil using a combined spinal-epidural technique. An effective dose was defined by the occurrence of no hypotension (defined as a decrease in systolic blood pressure by ≥20% below baseline and to <90 mm Hg) during the interval from the initiation of spinal anesthesia to delivery of the infant. Values for ED50 and ED90 of prophylactic phenylephrine were calculated using probit analysis., Results: Hypotension occurred in 13/20, 8/20, 2/20, and 1/20 patients in the groups that received phenylephrine infusion at 0.25, 0.375, 0.5, or 0.625 µg/kg/min, respectively. The calculated values for ED50 and ED90 were 0.31 (95% CI, 0.24-0.36) and 0.54 (95% CI, 0.46-0.76) µg/kg/min, respectively. No difference was found in the incidence of adverse effects and neonatal outcomes among groups., Conclusions: Under the conditions of this study, when phenylephrine was given as a fixed-rate prophylactic infusion during spinal anesthesia for cesarean delivery to prevent hypotension, the values for ED50 and ED90 were 0.31 (95% CI, 0.24-0.36) and 0.54 (95% CI, 0.46-0.76) µg/kg/min, respectively.

Background: Phenylephrine is the preferred vasopressor for the prevention and treatment of spinal anaesthesia-induced hypotension during caesarean section, because studies on low-risk elective patients found it to have a less detrimental effect on umbilical artery pH compared with ephedrine. However, limited data exist from high-risk parturients and parturients with uteroplacental insufficiency., Methods: We systematically searched for randomised, controlled, double-blinded trials of these two vasopressors in high-risk caesarean sections. We applied conventional meta-analysis, trial sequential analysis, computing the required information size that would exclude type I and II errors, contour-enhanced funnel plot testing for publication bias, meta-regression to assess the dose-response relationship, and the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE). The incidence of fetal acidosis (umbilical arterial pH <7.2) was the primary outcome., Results: Eight trials (712 patients) with low risk of bias were identified. Pooling six studies of patients with preeclampsia and other reasons for fetal compromise, as well as subgroup analysis of the preeclampsia studies, revealed no significant differences in the incidence of fetal acidosis. Trial sequential analysis showed that the required information size was not reached. The funnel plot was not suggestive of publication bias. Meta-regression showed no dose-response relationship. The GRADE score was moderate quality., Conclusions: Despite several studies and a large number of patients there was insufficient evidence to make a recommendation for choice of vasopressor in high-risk caesarean section. Trials with adequate power to detect differences in the incidence of fetal acidosis between ephedrine and phenylephrine are required to provide evidence-based guidance., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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.

Background: We previously described the use of closed-loop feedback computer-controlled infusion of phenylephrine for maintaining blood pressure (BP) during spinal anesthesia for cesarean delivery. In this study, we report a modified system in which phenylephrine is delivered by intermittent boluses rather than infusion. We hypothesized that the use of computer-controlled boluses would result in more precise control of BP compared with infusions., Methods: Two hundred fourteen healthy patients having spinal anesthesia for elective cesarean delivery were randomized to have their systolic BP maintained by phenylephrine administered by computer-controlled continuous infusion or computer-controlled intermittent boluses. From induction of anesthesia until the time of uterine incision, a noninvasive BP monitor was set to cycle at 1-minute intervals. In the infusion group, the infusion rate was automatically adjusted after each BP measurement using a previously described algorithm. In the bolus group, the algorithm was modified so that the mass of drug that would have been delivered over 1 minute was instead injected as a rapid intravenous bolus after each BP measurement. The precision of BP control was assessed using performance error calculations and compared between groups, with the primary outcome defined as median absolute performance error, and the latter being a measure of inaccuracy showing an average of the magnitudes of the differences of measured BP values above or below the target values., Results: The precision of BP control was greater, as shown by smaller values for median absolute performance error, in the bolus group (median 4.38 [quartiles 3.22, 6.25] %) versus the infusion group (5.39 [4.12, 7.04] %, P = .008). In the bolus group, phenylephrine consumption was smaller; this was associated with smaller values for median performance error compared with the continuous infusion group (P < .001), which indicates that values for systolic BP, averaged over time, were slightly lower in the bolus group. There were no differences in cardiac output, nausea or vomiting, or neonatal outcome between groups., Conclusions: We confirmed the hypothesis that BP control was more precise when computer-controlled phenylephrine was delivered using intermittent boluses rather than continuous infusion. However, the difference between groups was small and was not associated with any difference in clinical outcomes. In the infusion group, greater doses of phenylephrine were delivered, which was related to the time taken for the noninvasive BP monitor to complete measurements. The use of intermittent boluses may be a useful alternative in the design of closed-loop vasopressor systems.

Closed-loop feedback computer-controlled vasopressor infusion has been previously described for maintaining blood pressure during spinal anaesthesia for caesarean section but there are limited data available comparing the relative performance of different vasopressors. The aim of this study was to compare the performance of norepinephrine versus phenylephrine in this system. Data from a randomized, two-arm parallel group, double-blinded controlled trial were reanalyzed. 104 patients scheduled for elective caesarean section under spinal anaesthesia were randomized to receive computer-controlled closed-loop infusion of either norepinephrine 5 µg ml -1 or phenylephrine 100 µg ml -1 . This was started immediately after induction of spinal anaesthesia and used an algorithm designed to maintain systolic blood pressure near baseline until fetal delivery. Performance error calculations were used to compare the performance of the two vasopressors. The primary outcome was defined as the median absolute performance error. Median performance error, wobble and divergence were also compared. Median absolute performance error was smaller in the norepinephrine group (median 3.79 [interquartile range 2.82-5.17] %) versus the phenylephrine group (4.70 [3.23-6.57] %, P = 0.028). In addition, median performance error was smaller (0.75 [-1.56-2.52] %) versus 2.61 [0.83-4.57] %, P = 0.002) and wobble was smaller (2.85 [2.07-5.17] %) versus 3.39 [2.62-4.90] %, P = 0.028) in the norepinephrine group versus the phenylephrine group. Divergence was similar between groups. The precision of the control of blood pressure was greater with norepinephrine compared with phenylephrine at the drug concentrations used.

Background: During spinal anesthesia for cesarean delivery, phenylephrine can cause reflexive decreases in maternal heart rate and cardiac output. Norepinephrine has weak β-adrenergic receptor agonist activity in addition to potent α-adrenergic receptor activity and therefore may be suitable for maintaining blood pressure with less negative effects on heart rate and cardiac output compared with phenylephrine., Methods: In a randomized, double-blinded study, 104 healthy patients having cesarean delivery under spinal anesthesia were randomized to have systolic blood pressure maintained with a computer-controlled infusion of norepinephrine 5 μg/ml or phenylephrine 100 μg/ml. The primary outcome compared was cardiac output. Blood pressure heart rate and neonatal outcome were also compared., Results: Normalized cardiac output 5 min after induction was greater in the norepinephrine group versus the phenylephrine group (median 102.7% [interquartile range, 94.3 to 116.7%] versus 93.8% [85.0 to 103.1%], P = 0.004, median difference 9.8%, 95% CI of difference between medians 2.8 to 16.1%). From induction until uterine incision, for norepinephrine versus phenylephrine, systolic blood pressure and stroke volume were similar, heart rate and cardiac output were greater, systemic vascular resistance was lower, and the incidence of bradycardia was smaller. Neonatal outcome was similar between groups., Conclusions: When given by computer-controlled infusion during spinal anesthesia for cesarean delivery, norepinephrine was effective for maintaining blood pressure and was associated with greater heart rate and cardiac output compared with phenylephrine. Further work would be of interest to confirm the safety and efficacy of norepinephrine as a vasopressor in obstetric patients.

Background: Phenylephrine given during spinal anaesthesia for caesarean delivery often induces a decrease in heart rate which may decrease cardiac output. Anticholinergic drugs may be given to attenuate this effect but may also cause more labile blood pressure. This study evaluated the effects of glycopyrrolate pre-treatment on non-invasively measured cardiac output and accuracy of blood pressure control., Methods: At induction of spinal anaesthesia for caesarean delivery, 104 patients randomly received intravenous glycopyrrolate 4μg/kg or saline placebo. Systolic blood pressure, measured at 1-min intervals, was maintained near baseline using closed-loop feedback computer-controlled phenylephrine infusion with crystalloid cohydration. Cardiac output and stroke volume were measured using suprasternal Doppler ultrasonography at baseline and 5-min intervals for 20min. Blood pressure control was assessed using performance error calculations., Results: Eleven patients were excluded. Patients who received glycopyrrolate (n=45) had greater cardiac output over time (P<0.001), greater heart rate over time (P<0.001), similar stroke volume over time (P=0.95), and lower median phenylephrine infusion rate (P=0.006) compared with control (n=48). There was no difference in the incidence of hypotension between groups. Analysis of blood pressure control showed greater positive bias, greater inaccuracy and greater wobble in the glycopyrrolate group (all P<0.05). Neonatal outcome was similar between groups., Conclusions: Glycopyrrolate 4μg/kg given at the start of a phenylephrine infusion increased heart rate and cardiac output but also decreased accuracy of blood pressure control, increased the incidence of hypertension and caused an increased incidence of dry mouth postoperatively compared with control., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Closed-loop feedback computer-controlled infusion has not been described for administering phenylephrine to maintain arterial pressure (AP) during spinal anaesthesia for caesarean delivery. We aimed to compare AP control using this automated system with a previously described manual infusion system., Methods: We randomly allocated 222 healthy subjects having spinal anaesthesia for scheduled caesarean delivery to have systolic AP maintained near baseline with phenylephrine (100 µg ml(-1)) by computer-controlled infusion utilizing a proportional algorithm or manual-controlled infusion utilizing an on-off algorithm. AP control was assessed by comparing the proportion of systolic AP measurements within ±20% of baseline and by performance error (PE) calculations., Results: A total of 212 subjects finished the study. In the computer-control group, 97% of systolic AP recordings fell within ±20% of baseline compared with 95% in the manual-control group (P=0.0004). For computer-control compared with manual-control, wobble was smaller [median 3.5 (inter-quartile range 2.5-4.8)% vs 4.2 (3.3-5.9)%, P=0.003], but there was no difference in the median PE [2.9 (0.3-4.7)% vs 1.9 (0-4.2)%], median absolute PE [4.7 (3.5-5.6)% vs 4.7 (3.8-6.7)%], or divergence [-0.01 (-0.03-0)% vs -0.06 (-0.26-0.08)%]. Fewer interventions per subject for controlling AP were required in the computer-control group [2 (2-2) vs 10 (8-13), P<0.001]. There were no differences in measured clinical outcomes., Conclusions: Within the constraints of the studied algorithms, closed-loop feedback computer-controlled phenylephrine infusion provided better AP control with fewer interventions required compared with manual-controlled infusion.

Background: Use of ephedrine in obstetric patients is associated with depression of fetal acid-base status. The authors hypothesized that the mechanism underlying this is transfer of ephedrine across the placenta and stimulation of metabolism in the fetus., Methods: A total of 104 women having elective Cesarean delivery under spinal anesthesia randomly received infusion of phenylephrine (100 microg/ml) or ephedrine (8 mg/ml) titrated to maintain systolic blood pressure near baseline. At delivery, maternal arterial, umbilical arterial, and umbilical venous blood samples were taken for measurement of blood gases and plasma concentrations of phenylephrine, ephedrine, lactate, glucose, epinephrine, and norepinephrine., Results: In the ephedrine group, umbilical arterial and umbilical venous pH and base excess were lower, whereas umbilical arterial and umbilical venous plasma concentrations of lactate, glucose, epinephrine, and norepinephrine were greater. Umbilical arterial Pco2 and umbilical venous Po2 were greater in the ephedrine group. Placental transfer was greater for ephedrine (median umbilical venous/maternal arterial plasma concentration ratio 1.13 vs. 0.17). The umbilical arterial/umbilical venous plasma concentration ratio was greater for ephedrine (median 0.83 vs. 0.71)., Conclusions: Ephedrine crosses the placenta to a greater extent and undergoes less early metabolism and/or redistribution in the fetus compared with phenylephrine. The associated increased fetal concentrations of lactate, glucose, and catecholamines support the hypothesis that depression of fetal pH and base excess with ephedrine is related to metabolic effects secondary to stimulation of fetal beta-adrenergic receptors. Despite historical evidence suggesting uteroplacental blood flow may be better maintained with ephedrine, the overall effect of the vasopressors on fetal oxygen supply and demand balance may favor phenylephrine.

Summary: In a randomised, double-blinded study, we compared boluses of phenylephrine 100 microg with ephedrine 10 mg for treating hypotension (systolic blood pressure < 100 mmHg) in 204 patients having non-elective Caesarean section under spinal anaesthesia. Umbilical arterial (UA) and venous (UV) pH and base excess were similar between groups. In the ephedrine group, UA lactate concentration was higher (median 2.6 [interquartile range 2.3-3.3] vs 2.4 [1.9-3.0] mmolxl(-1), p = 0.002) and UV lactate concentration was higher (2.5 [2.2-3.2] vs 2.3 [1.9-2.8] mmolxl(-1), p = 0.016) and more patients had nausea or vomiting (12.7% vs 3.9%, p = 0.02). Clinical neonatal outcome was similar. Of the protocol-compliant patients (n = 148), UA Po(2) and UV Po(2) were lower in the phenylephrine group although oxygen content was similar. We conclude that phenylephrine and ephedrine are both suitable vasopressors for use in non-elective Caesarean sections.

Background: Phenylephrine and ephedrine are both used to maintain arterial blood pressure during spinal anesthesia for cesarean delivery. Usually, either drug is given alone but several previous studies have described combining the drugs. However, the effect of varying the proportion of vasopressors in such combinations has not been reported., Methods: One-hundred-twenty-five parturients having spinal anesthesia for elective cesarean delivery were randomized to receive an IV infusion of phenylephrine and ephedrine combined in one of five different concentration ratios. Assuming phenylephrine 100 microg to be approximately equipotent to ephedrine 8 mg, the groups contained the proportional potency equivalent of 100%, 75%, 50%, 25% or 0% of phenylephrine and 0%, 25%, 50%, 75% or 100%, respectively, of ephedrine. The infusions were adjusted to maintain systolic blood pressure (SBP) near baseline until uterine incision. Hemodynamic changes and umbilical cord blood gases were compared., Results: As the proportion of phenylephrine decreased and proportion of ephedrine increased among the groups, the following significant trends were detected: the incidences of hypotension and nausea/vomiting increased, the median magnitude of deviations of SBP above or below baseline and the bias for SBP to be above baseline increased, maternal heart rate was faster, fetal pH and base excess decreased, umbilical arterial oxygen content decreased and umbilical venous Po2 increased., Conclusions: When varying combinations of phenylephrine and ephedrine were given by infusion to maintain arterial blood pressure during spinal anesthesia for cesarean delivery, as the proportion of phenylephrine decreased and the proportion of ephedrine increased, hemodynamic control was reduced and fetal acid-base status was less favorable. Combinations of phenylephrine and ephedrine appear to have no advantage compared with phenylephrine alone when administered by infusion for the prevention of hypotension associated with spinal anesthesia for cesarean delivery.

We describe the novel use of a closed-loop feedback computer-controlled infusion of phenylephrine for maintaining blood pressure in 53 patients having spinal anaesthesia for elective caesarean section. A simple on-off algorithm was used that activated an intravenous phenylephrine infusion at 100 microg.min(-1) when systolic blood pressure was less than or equal to baseline and stopped the infusion when systolic blood pressure exceeded baseline. Up to uterine incision, 94.6% of all systolic blood pressure measurements were within the range (baseline +/- 20%). Seven patients (13.2%) had one or more episodes of hypotension (systolic blood pressure < 80% of baseline) and 23 patients (37.7%) had one or more episodes of hypertension (systolic blood pressure > 120% of baseline). No patient had nausea or vomiting and in no case was umbilical arterial blood pH < 7.2. Calculated system performance parameters were comparable with those of previously published closed-loop systems and provide a reference for the potential development and comparison of more advanced algorithms.

Background: Many methods for preventing hypotension during spinal anesthesia for cesarean delivery have been investigated, but no single technique has proven to be effective and reliable. This randomized study studied the efficacy of combining simultaneous rapid crystalloid infusion (cohydration) with a high-dose phenylephrine infusion., Methods: Nonlaboring patients scheduled to undergo elective cesarean delivery received an intravenous infusion of 100 mug/min phenylephrine that was started immediately after spinal injection and titrated to maintain systolic blood pressure near baseline values until uterine incision. In addition, patients received infusion of lactated Ringer's solution that was given either rapidly (group 1, n = 57) or at a minimal maintenance rate (group 0, n = 55). Maternal hemodynamic changes and neonatal condition were compared., Results: Six patients were excluded from analysis. Only 1 of 53 patients (1.9% [95% confidence interval, 0.3-9.9%]) in group 1 experienced hypotension versus 15 of 53 patients (28.3% [95% confidence interval, 18.0-41.6%]) in group 0 (P = 0.0001). Compared with group 0, patients in group 1 had greater values for the following: serial measurements of systolic blood pressure (P = 0.02), minimum recorded systolic blood pressure (P = 0.0002), and minimum recorded heart rate (P = 0.013). Total phenylephrine consumption was smaller in group 1 compared with group 0 (P = 0.008). Neonatal outcome and maternal side effects were similar between groups., Conclusions: Combination of a high-dose phenylephrine infusion and rapid crystalloid cohydration is the first technique to be described that is effective for preventing hypotension during spinal anesthesia for cesarean delivery.

Background: During spinal anaesthesia for Caesarean section, the optimal phenylephrine regimen and the optimal blood pressure (BP) to which it should be titrated are undetermined. The ideal regimen would balance efficacy for maintaining uteroplacental perfusion pressure against potential for uteroplacental vasoconstriction, both of which may affect fetal acid-base status. We compared phenylephrine infusion regimens based on three different BP thresholds., Methods: After intrathecal injection, we infused phenylephrine 100 microg min(-1) for 2 min. Then, until delivery, we infused phenylephrine whenever systolic BP (SBP), measured every 1 min, was below a randomly assigned percentage of baseline: 100% (Group 100, n=25), 90% (Group 90, n=25) or 80% (Group 80, n=24). We compared umbilical blood gases, Apgar scores and maternal haemodynamics and symptoms., Results: Patients in Group 100 had fewer episodes [median 0 (range 0-8)] of hypotension (SBP <80% baseline) compared with Group 80 [5 (0-18)] and Group 90 [2 (0-7)] (P<0.001 in each instance). Total dose of phenylephrine was greater in Group 100 [median 1520 microg (interquartile range 1250-2130 microg)] compared with Group 90 [1070 (890-1360) microg] and Group 80 [790 (590-950) microg]. Umbilical arterial pH was greater in Group 100 [mean 7.32 (95% confidence interval 7.31-7.34)] than in Group 80 [7.30 (7.28-7.31)] (P=0.034). No patient had umbilical arterial pH <7.2. In Group 100, 1/24 (4%) patients had nausea or vomiting compared with 4/25 (16%) in Group 90 and 10/25 (40%) in Group 80 (P=0.006)., Conclusions: For optimal management, phenylephrine should be titrated to maintain maternal BP at near-baseline values.

Unlabelled: In a randomized, double-blinded, controlled trial, we investigated the prophylactic infusion of IV phenylephrine for the prevention of hypotension during spinal anesthesia for cesarean delivery. Immediately after intrathecal injection, phenylephrine was infused at 100 microg/min (n = 26) for 3 min. From that point until delivery, phenylephrine was infused at 100 microg/min whenever systolic arterial blood pressure (SAP), measured each minute, was less than baseline. A control group (n = 24) received IV bolus phenylephrine 100 microg after each measurement of SAP <80% of baseline. Phenylephrine infusion decreased the incidence (6 [23%] of 26 versus 21 [88%] of 24; P < 0.0001), frequency, and magnitude (median minimum SAP, 106 mm Hg; interquartile range, 95-111 mm Hg; versus median, 80 mm Hg; range, 73-93 mm Hg; P < 0.0001) of hypotension compared with control. Heart rate was significantly slower over time in the infusion group compared with the control group (P < 0.0001). Despite a large total dose of phenylephrine administered to the infusion group compared with the control group (median, 1260 microg; interquartile range, 1010-1640 microg; versus median, 450 microg; interquartile range, 300-750 microg; P < 0.0001), umbilical cord blood gases and Apgar scores were similar. One patient in each group had umbilical arterial pH <7.2. Prophylactic phenylephrine infusion is a simple, safe, and effective method of maintaining arterial blood pressure during spinal anesthesia for cesarean delivery., Implications: In patients receiving spinal anesthesia for elective cesarean delivery, a prophylactic infusion of phenylephrine 100 microg/min decreased the incidence, frequency, and magnitude of hypotension with equivalent neonatal outcome compared with a control group receiving IV bolus phenylephrine.

Unlabelled: This quantitative systematic review compared the efficacy and safety of ephedrine with phenylephrine for the prevention and treatment of hypotension during spinal anesthesia for cesarean delivery. Seven randomized controlled trials (n = 292) were identified after a systematic search of electronic databases (MEDLINE, EMBASE, The Cochrane Controlled Trials Registry), published articles, and contact with authors. Outcomes assessed were maternal hypotension, hypertension and bradycardia, and neonatal umbilical cord blood pH values and Apgar scores. For the management (prevention and treatment) of maternal hypotension, there was no difference between phenylephrine and ephedrine (relative risk [RR] of 1.00; 95% confidence interval [CI], 0.96-1.06). Maternal bradycardia was more likely to occur with phenylephrine than with ephedrine (RR of 4.79; 95% CI, 1.47-15.60). Women given phenylephrine had neonates with higher umbilical arterial pH values than those given ephedrine (weighted mean difference of 0.03; 95% CI, 0.02-0.04). There was no difference between the two vasopressors in the incidence of true fetal acidosis (umbilical arterial pH value of <7.2; RR of 0.78; 95% CI, 0.16-3.92) or Apgar score of <7 at 1 and 5 min. This systematic review does not support the traditional idea that ephedrine is the preferred choice for the management of maternal hypotension during spinal anesthesia for elective cesarean delivery in healthy, nonlaboring women., Implications: Phenylephrine and ephedrine to manage hypotension during spinal anesthesia for elective cesarean delivery were compared in this systematic review. Women given ephedrine had neonates with lower umbilical cord blood pH values compared with those given phenylephrine. However, no differences in the incidence of fetal acidosis (pH value of <7.2) or neonatal Apgar scores were found.