Randomized Double-Blinded Comparison of Intermittent Boluses Phenylephrine and Norepinephrine for the Treatment of Postspinal Hypotension in Patients with Severe Pre-Eclampsia During Cesarean Section.

Background: Norepinephrine has fewer negative effects on heart rate (HR) and cardiac output (CO) for treating postspinal hypotension (PSH) compared with phenylephrine during cesarean section. However, it remains unclear whether fetuses from patients with severe pre-eclampsia could benefit from the superiority of CO. The objective of this study was to compare the safety and efficacy of intermittent intravenous boluses of phenylephrine and norepinephrine used in equipotent doses for treating postspinal hypotension in patients with severe pre-eclampsia during cesarean section. Methods: A total of 80 patients with severe pre-eclampsia who developed PSH predelivery during cesarean section were included. Eligible patients were randomized at a 1:1 ratio to receive either phenylephrine or norepinephrine for treating PSH. The primary outcome was umbilical arterial pH. Secondary outcomes included other umbilical cord blood gas values, Apgar scores at 1 and 5 min, changes in hemodynamic parameters including CO, mean arterial pressure (MAP), HR, stroke volume (SV), and systemic vascular resistance (SVR), the number of vasopressor boluses required, and the incidence of bradycardia, hypertension, nausea, vomiting, and dizziness. Results: No significant difference was observed in umbilical arterial pH between the phenylephrine and norepinephrine groups (7.303±0.38 vs 7.303±0.44, respectively; P=0.978). Compared with the phenylephrine group, the overall CO (P=0.009) and HR (P=0.015) were greater in the norepinephrine group. The median [IQR] total number of vasopressor boluses required was comparable between the two groups (2 [1 to 3] and 2 [1 to 3], respectively; P=0.942). No significant difference was found in Apgar scores or the incidence of maternal complications between groups. Conclusion: A 60 µg bolus of phenylephrine and a 4.5 µg bolus of norepinephrine showed similar neonatal outcomes assessed by umbilical arterial pH and were equally effective when treating PSH during cesarean section in patients with severe pre-eclampsia. Norepinephrine provided a higher maternal CO and a lower incidence of bradycardia.

Comparative dose-response study of intrathecal hyperbaric ropivacaine for cesarean delivery in preterm singleton versus twin pregnancies.

INTRODUCTION: Previously, we demonstrated that patients with full-term singletons and preterm twins require similar dose of intrathecal hyperbaric ropivacaine. However, these findings may be attributable to enrolled patients with preterm twin pregnancies. In this study, we aimed to determine the intrathecal dose requirements of hyperbaric ropivacaine for twins and singletons at equal gestational ages. METHODS: We enrolled 75 patients with preterm singletons and 75 patients with preterm twins scheduled for cesarean delivery under combined spinal-epidural anesthesia in this two-arm parallel, randomized, double-blind, dose-response study. Patients with singletons and twins were randomly assigned to receive one of five different doses of hyperbaric ropivacaine: 10, 12, 14, 16, or 18 mg. A probit regression model was used to determine the dose effective in 50% of patients (ED50) and dose effective in 90% of patients (ED90) values. The relative median potency was calculated to compare the ED50 between patients with twins and singletons. RESULTS: Intrathecal ropivacaine ED50 and ED90 (with 95% CI) in patients with preterm singletons were 9.9 (7.2 to 11.5) mg and 16.8 (14.5 to 22.9) mg, respectively. In patients with preterm twins, these values were 9.2 (95% CI 6.4 to 10.8) mg and 15.6 (95% CI 13.6 to 20.6) mg. Between patients with preterm twins and preterm singletons, the relative potency (ED50 ratios) was 0.933 (95% CI 0.72 to 1.15). CONCLUSIONS: During preterm gestation, intrathecal hyperbaric ropivacaine dose requirements for scheduled cesarean delivery were not different between patients with twins and singletons. TRIAL REGISTRATION NUMBER: ChiCTR2100051382.

Comparative study on the manually-controlled variable-rate versus fixed-rate infusion of norepinephrine for preventing hypotension during spinal anesthesia for cesarean delivery.

STUDY OBJECTIVE: Previous studies have shown that prophylactic norepinephrine infusion is superior to intermittent bolus administration in preventing post-spinal hypotension. Nevertheless, it is still controversial whether manually-controlled variable-rate infusion is more effective than fixed-rate infusion. The purpose of the present study was to compare the efficacy of variable-rate infusion and fixed-rate infusion of norepinephrine for prophylaxis against maternal hypotension and maintaining hemodynamic stability during spinal anesthesia for cesarean delivery to determine more effective mode for clinical practice. DESIGN: A prospective randomized, controlled study. SETTING: Operating room, Women's Hospital, Zhejiang University School of Medicine. PATIENTS: A total of 161 parturients scheduled for elective cesarean delivery with spinal anesthesia were randomized into Group F (fixed-rate infusion) and Group V (variable-rate infusion). INTERVENTIONS: Parturients received prophylactic norepinephrine infusion concurrent with the intrathecal injection at rate started at 0.05 µg/kg/min. In Group F, norepinephrine was administered continuously at a fixed (on-off) rate, and a bolus of norepinephrine 5 µg or 10 µg was given when systolic blood pressure (SBP) decreased by 20% or more of baseline. In Group V, manually adjusted norepinephrine infusion within the range 0-0.14 µg/kg/min, according to SBP at 1-min intervals until delivery, aim to maintain values close to the baseline. MEASUREMENTS: During the study period, the incidence of maternal hypotension, hemodynamic performance, the number of physician interventions, reactive hypertension, bradycardia, nausea, vomiting, norepinephrine cumulative dose (before delivery), and neonatal outcomes were recorded. MAIN RESULTS: The incidence of maternal hypotension was significantly lower in Group V than that in Group F (9% versus 30%) (P < 0.001). No significant difference was found in the serial changes in SBP and heart rate (HR) for the first 15 min. Group V showed higher frequency of physician interventions compared with the Group F (P < 0.001). The incidence of hypertension, severe hypotension, nausea, vomiting, bradycardia, norepinephrine cumulative dose, and neonatal outcome were comparable between the two groups. CONCLUSION: When norepinephrine was infused at an initial dose of 0.05 µg/kg/min for preventing hypotension during spinal anesthesia for cesarean delivery, due to technical limitations of inadequate dose design in this study, neither a variable-rate infusion (need more physician intervention) nor a fixed-rate infusion regimen (experience more transient hypotension) was optimal. However, in terms of clinical importance, how to prevent the parturients from experiencing more incidence of hypotension might be a greater concern for anesthesiologists.

Determination of the 90% Effective Dose of Phenylephrine Boluses to Treat Spinal Anesthesia-Induced Hypotension in Patients with Severe Preeclampsia during Cesarean Delivery: A Pilot Study.

PURPOSE: Treatment of spinal anesthesia-induced hypotension in patients with severe preeclampsia assumes special concern as hypotension may further reduce placental perfusion. Phenylephrine is still the first-line vasopressor for treating spinal anesthesia-induced hypotension. However, the optimal dose of phenylephrine used as intravenous (IV) boluses in patients with severe preeclampsia has not been clearly determined. We aim to calculate the 90% effective dose (ED90) of phenylephrine as IV boluses for treating spinal anesthesia-induced hypotension in patients with severe preeclampsia undergoing cesarean delivery. PATIENTS AND METHODS: Forty patients with severe preeclampsia were enrolled in this prospective sequential allocation dose-finding trial. Using the biased coin up-and-down (BCUD) method, all patients in our study received an IV bolus phenylephrine of either 40, 50, 60, 70, or 80 µg when the mean arterial pressure (MAP) decreased to less than 80% of the baseline level and the ED90 was determined. The primary outcome was the success of the assigned phenylephrine bolus to maintain the MAP at or above 80% of baseline value between the induction of spinal anesthesia and delivery of the fetus. Secondary outcomes included hypertension, nausea, vomiting, bradycardia, upper sensory level of anesthesia, umbilical blood gases, and Apgar score. Estimating of the ED90 with 95% confidence interval (CI) was achieved by isotonic regression method. RESULTS: The ED90 of phenylephrine was estimated as 62.00 µg (95% CI=50.00-67.40 µg) using the isotonic regression method. No patients enrolled in our study experienced bradycardia and those patients who developed hypertension were all observed at the dose level 70 µg. CONCLUSION: For clinical practice, we recommend that phenylephrine 60 µg may be both effective and safe for treatment of spinal anesthesia-induced hypotension in severe preeclampsia during cesarean delivery.