Comparison of Two Vasopressor Protocols for Preventing Hypotension Post-Spinal Anesthesia During Cesarean Section: A Randomized Controlled Trial

Comparison of Two Vasopressor Protocols for Preventing Hypotension Post-Spinal Anesthesia During Cesarean Section: A Randomized Controlled Trial

Spinal anesthesia is the preferred technique for cesarean section due to its efficacy and safety. However, post-spinal anesthesia hypotension is a common complication, occurring in 70% to 80% of cases without pharmacological prophylaxis. This condition can lead to maternal complications such as nausea, vomiting, and fetal compromise. Various prophylactic measures, including fluid preload, lateral tilt, and vasoactive agents, are employed to mitigate this risk. Among vasoactive drugs, ephedrine and phenylephrine are commonly used. However, ephedrine has a slow onset and prolonged duration, making blood pressure titration difficult, while phenylephrine is associated with a high incidence of bradycardia. Additionally, ephedrine easily crosses the placenta, potentially causing fetal tachycardia and acidosis. Norepinephrine, a potent α-adrenergic receptor agonist with mild β-adrenergic receptor activity, has recently been introduced for preventing post-spinal hypotension. This study aimed to compare the efficacy of norepinephrine infusion and ephedrine bolus in preventing post-spinal hypotension in parturients undergoing elective cesarean section.

The study was a single-center, randomized, double-blinded clinical trial conducted at Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China. Ethical approval was obtained from the Institutional Review Board of Xijing Hospital, and the trial was registered at ClinicalTrials.gov (NCT02542748). Written informed consent was obtained from all participants. The study included parturients aged 18 years or older with American Society of Anesthesiologists physical status class 1 or 2, full-term singleton pregnancies, and scheduled elective cesarean section under spinal anesthesia. Exclusion criteria included cardiovascular disease, pregnancy-induced hypertension, pre-eclampsia, gestational diabetes requiring insulin, body mass index greater than 40 kg/m², suspicion of fetal distress, and abnormal placentation. Patients were also excluded if the dermatomal level of the spinal block exceeded the fourth thoracic level or was lower than the tenth thoracic level, or if spinal anesthesia failed.

Patients were randomized into two groups using a computer-generated sequence. The norepinephrine group received a continuous infusion of norepinephrine at 0.05 mg·kg⁻¹·min⁻¹ initiated just before spinal anesthesia and continued for 30 minutes. The ephedrine group received an ephedrine bolus of 0.15 mg/kg just before spinal anesthesia. Rescue boluses of 5 mg norepinephrine or 5 mg ephedrine were administered in the respective groups whenever hypotension occurred. The primary outcome was the incidence of hypotension within 30 minutes of spinal anesthesia administration. Secondary outcomes included maternal and neonatal outcomes 30 minutes after spinal block, and neonatal cerebral oxygenation 10 minutes after birth.

A total of 190 patients were enrolled, with 177 included in the final analysis. The norepinephrine group had a significantly lower incidence of hypotension compared to the ephedrine group (29.5% vs. 44.9%, odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.28–0.95, P = 0.034). The norepinephrine group also had a lower frequency of tachycardia (OR: 0.22, 95% CI: 0.11–0.44, P < 0.001) and fewer incidences of nausea and vomiting (OR: 0.28, 95% CI: 0.11–0.70, P = 0.004). There were no significant differences in Apgar scores and umbilical arterial blood gas analysis between the two groups. However, neonatal cerebral regional saturations were significantly higher in the norepinephrine group than in the ephedrine group (mean difference: 2.0%, 95% CI: 0.55%–3.45%, P = 0.008).

The results indicate that norepinephrine infusion is more effective than ephedrine bolus in reducing post-spinal hypotension, tachycardia, and nausea during cesarean section. The study also suggests potential neonatal benefits associated with norepinephrine infusion, as evidenced by higher neonatal cerebral oxygenation levels. These findings are consistent with previous studies comparing norepinephrine and ephedrine, although this study uniquely employed norepinephrine infusion rather than bolus administration.

Norepinephrine’s advantages over ephedrine are likely due to its faster onset and shorter duration, making it more suitable for infusion. Previous studies have shown that titrated norepinephrine infusion provides tighter blood pressure control and reduces hypotension-related complications compared to bolus administration. The fixed-rate infusion of 0.05 mg·kg⁻¹·min⁻¹ used in this study was effective and did not result in significant adverse effects. The potency ratio of norepinephrine to ephedrine was estimated to be 1000:1, based on previous studies comparing their efficacy in maintaining blood pressure.

The study also highlighted the importance of maintaining stable maternal blood pressure to prevent complications such as nausea and vomiting. Intra-operative hypotension can lead to cerebral and gut hypoperfusion, stimulating the release of serotonin from the vomiting center in the brainstem. Tight blood pressure control within 100% of baseline has been shown to reduce nausea and vomiting. The norepinephrine group experienced fewer incidences of nausea and vomiting, likely due to better blood pressure maintenance.

Neonatal outcomes were comparable between the two groups, with no significant differences in Apgar scores and umbilical arterial blood gas analysis. However, the norepinephrine group had higher neonatal cerebral regional saturations, suggesting better cerebral oxygenation. This finding is significant as cerebral oxygenation is crucial for neonatal transition and can impact long-term neurodevelopmental outcomes. The clinical significance of higher cerebral regional saturations in the norepinephrine group warrants further research to determine if it translates to improved neonatal outcomes.

The study had some limitations. It did not compare cardiac output between the two groups, which could provide additional insights into the hemodynamic effects of norepinephrine and ephedrine. Non-invasive methods for measuring cardiac output, such as transthoracic echocardiography, could be employed in future studies. Additionally, cerebral regional saturation values were not measured in the first two minutes after birth due to other neonatal procedures being performed. However, data from 2 to 10 minutes after birth were complete and showed significant differences between the groups.

In conclusion, norepinephrine fixed-rate infusion is more effective than ephedrine bolus in preventing post-spinal hypotension during cesarean section, with potential neonatal benefits. The study supports the use of norepinephrine infusion for maintaining maternal blood pressure and reducing complications such as tachycardia and nausea. Further research is needed to optimize the norepinephrine infusion regimen and explore its long-term neonatal benefits.

doi.org/10.1097/CM9.0000000000001404

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