去甲肾上腺素预防剖宫产脊髓麻醉后低血压的最佳输注速率：一项采用上下序贯分配的随机对照试验
贵州医科大学 麻醉与心脏电生理课题组
翻译：周倩 编辑：周倩 审校：曹莹
最近有研究表明，在预防剖宫产脊髓麻醉后低血压方面，去甲肾上腺素与去氧肾上腺素一样有效。此外，与去氧肾上腺素相比，去甲肾上腺素在维持心率 (HR) 和心输出量 (CO)方面可能更胜一筹。最近的一项研究表明，单次静脉推注去甲肾上腺素的效力约为去氧肾上腺素的13倍，但该效价比是否适用于持续输注方式尚不明确。因此，去甲肾上腺素的最佳输注速率仍然未知。我们的目的是确定在剖宫产脊髓麻醉后，维持产妇收缩压在基线的20%以内所需的两种药物的中位有效剂量 (ED50：定义为预防50%受试者发生脊髓低血压所需的升压药输注速率)，并推导其相对效价比。
方法
60名接受择期剖宫产手术并使用标准化脊髓麻醉的健康患者被随机分为两组。第一组首例患者以60ml/h的输注速率(20µg/min）接受60ml0.9%生理盐水配制的1200µg去氧肾上腺素。第二组首例患者则以60ml/h的输注速率(1.6µg/min）接受60ml0.9%生理盐水配制的96µg去甲肾上腺素。采用上下序贯分配法，后续患者的升压剂量根据前一位患者的反应确定：若有效，则下一例患者减少150µg去氧肾上腺素(2.5µg/min）或12µg去甲肾上腺素(0.2µg/min）。若无效，则按相同幅度增加剂量。根据Dixon-Massey公式计算ED50值，并测量每搏输出量（SV）、心率（HR）和心输出量（CO）。
结果
去氧肾上腺素的ED50为12.7 µg/min（95% CI: 10.5–14.9），去甲肾上腺素的ED50为1.01 µg/min（95% CI: 0.84–1.18），效价比为12.6（95% CI: 9.92–15.9）。两组间心率、每搏输出量和心输出量无显著差异。新生儿结局（APGAR评分、脐动静脉血气）组间也无统计学差异。
当以输注方式用于等效血压控制时，去甲肾上腺素的效价约为去氧肾上腺素的13倍。基于此结果，建议在剖宫产脊髓麻醉期间预防低血压时，去甲肾上腺素的预防性输注速率初始范围为1.9–3.8 µg/min。
原始文献：Khatoon F, Kocarev M, Fernando R, et al. Optimal Infusion Rate of Norepinephrine for Prevention of Spinal Hypotension for Cesarean Delivery: A Randomized Controlled Trial, Using Up-Down Sequential Allocation. Anesth Analg. 2025 Jul 1;141(1):17-25.
Optimal Infusion Rate of Norepinephrine for Prevention of Spinal Hypotension for Cesarean Delivery: A Randomized Controlled Trial, Using Up-Down Sequential Allocation
ABSTRACT
BACKGROUND: Norepinephrine has recently been suggested to be as effective as phenylephrine for the prevention of hypotension after spinal anesthesia for cesarean delivery. Moreover, compared to phenylephrine, norepinephrine may be superior in maintaining heart rate (HR) and consequently, cardiac output (CO). A recent study demonstrated that norepinephrine given as a single intravenous bolus is approximately 13 times more potent than phenylephrine. However, it is uncertain whether this finding can be applied when these vasopressors are administered as infusions. Therefore, the optimum infusion rate of norepinephrine remains unknown. We aimed to determine the median effective dose (ED 50 ; defined as the rate of vasopressor infusion required to prevent spinal hypotension in 50% of subjects) of both drugs needed to maintain maternal systolic blood pressure within 20% of the baseline after spinal anesthesia for cesarean delivery and to derive the relative potency ratio.
METHODS: Sixty healthy patients undergoing elective cesarean delivery with standardized spinal anesthesia were randomized into 2 groups. The first patient in group 1 received phenylephrine 1200 µg in normal saline 0.9% w/v 60 mL at 60 mL/h infusion rate (20 µg.min -1 ). The first patient in group 2 received norepinephrine 96 µg in normal saline 0.9% w/v 60 mL at 60 mL/h infusion rate (1.6 µg.min -1 ). Using up-down sequential allocation technique, the vasopressor dose for every subsequent patient was determined by the response in the previous patient. If effective, the next patient received a dose reduced by 150 µg of phenylephrine (2.5 µg.min -1 ) or 12 µg (0.2 µg.min -1 ) of norepinephrine. If ineffective, the dose for the next patient was increased by the same amount. The ED50s were determined according to the Dixon-Massey formula. Stroke volume (SV), HR, and CO were also measured.
RESULTS: The ED 50 was 12.7 µg.min -1 (95% CI, 10.5-14.9) for phenylephrine and 1.01 µg.min -1 (95% CI, 0.84-1.18) for norepinephrine, giving a potency ratio of 12.6 (95% CI, 9.92-15.9). HR, SV, and CO did not differ between the groups.
CONCLUSIONS: Norepinephrine is more potent than phenylephrine by a factor of approximately 13 when administered as infusion for equivalent maternal blood pressure control. Based on these findings, we recommend a variable rate prophylactic infusion of norepinephrine to be initiated at 1.9 to 3.8 µg.min – 1 for the management of hypotension during cesarean delivery under spinal anesthesia.