间歇快速静脉注射去氧肾上腺素和去甲肾上腺素防治剖宫产术中腰麻低血压的比较：随机对照试验
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Comparison of Intermittent Intravenous Boluses of Phenylephrine and Norepinephrine to Prevent and Treat Spinal-Induced Hypotension in Cesarean Deliveries: Randomized Controlled Trial
背景与目的
目前去氧肾上腺素 (PE)是预防和治疗剖宫产 (CD)术中腰麻低血压的首选血管升压药，然而，其使用常引起反射性心动过缓。去甲肾上腺素 (NE)因治疗低血压的同时可维持心率(HR)稳定，成为剖宫产术中的替代性血管升压药。新近研究表明，与PE相比，NE输注效果更好，但剖宫产术中快速注射等效剂量PE和NE的研究尚无报道。本研究假设，间歇快速注射等效剂量的PE及NE预防和治疗腰麻低血压时，与PE相比，NE可降低心动过缓的发生率。
方 法
本研究为双盲、随机临床试验，纳入于腰麻下行择期剖宫产的患者。当收缩压(SBP)低于正常值时，随机给患者注射去氧肾上腺素100 µg或去甲肾上腺素6 µg。除随机治疗外，如果收缩压低于正常值并且HR <60次/分，或者连续2次测量收缩压均<正常值80%，都要静脉注射麻黄碱。产前心动过缓(HR <50次/分)作为主要结果，次要结果包括低血压(SBP <正常值80%)、高血压(SBP >正常值120%)、心动过速(HR >正常值120%)、心动过缓发生次数≥2次、恶心、呕吐、脐动脉和脐静脉血气分析以及Apgar评分。
结 果
随机抽取112例患者，与PE组比较，NE组心动过缓的发生率较低（10.9% vs 37.5%；P<0.001 ； 95% CI：−26.8% [−41.8% 至−11.7%])。两组间心动过缓的发生次数同样存在差异(P=0.007)。进一步研究表明，PE组患者发生多发性心动过缓(发生≥2次)的风险高于NE组(PE组19.6% vs NE组3.6%；P=0.008)。与PE组相比，NE组患者需要注射麻黄碱补救的比例较低（NE组7.2% vs PE组21.4%；P <0.03 ；95% CI： −14.3% [−27.0%至−1.6%]）。两组间其它次要结果的发生率无差异。
结 论
间歇快速疗法预防和治疗剖宫产术中腰麻低血压时，与等效剂量去氧肾上腺素相比，去甲肾上腺素显著降低心动过缓的发生率。本研究推测，可能因心率和心输出量波动较小，剖宫产术中去甲肾上腺素产生的血流动力学曲线优于去氧肾上腺素。
原始文献摘要
Aidan MS, Naveed S,Kristi D，et al.Comparison of Intermittent Intravenous Boluses of Phenylephrine and Norepinephrine to Prevent and Treat Spinal-Induced Hypotension in Cesarean Deliveries: Randomized Controlled Trial[J].Anesth Analg,2018.
BACKGROUND: Phenylephrine (PE) is currently the vasopressor of choice to prevent and treat spinal-induced hypotension at cesarean delivery (CD). However, its use is often associated with reflex bradycardia. Norepinephrine (NE) has been put forward as an alternative vasopressor during CD due to its ability to treat hypotension while maintaining heart rate (HR). Recent studies have focused on the role of NE used as an infusion with favorable results compared to PE. No studies have compared equipotent bolus doses of PE and NE at CD. We hypothesized that when used in equipotent doses as an intermittent bolus regimen to prevent and treat spinal-induced hypotension, NE would result in a reduction in the incidence of bradycardia compared to PE.
METHODS: This was a double-blind, randomized clinical trial of women undergoing elective CD under spinal anesthesia. Women were randomized to receive either PE 100 µg or NE 6 µg when the systolic blood pressure (SBP) was below baseline. In addition to the randomized treatment, ephedrine was given intravenously to both groups if the SBP was below baseline and the HR <60 bpm or if the SBP was <80% of baseline for 2 consecutive readings. The primary outcome was bradycardia (HR <50 bpm) in the predelivery period. Secondary outcomes included hypotension (SBP <80% of baseline), hypertension (SBP >120% of baseline), tachycardia (HR >120% of baseline), ≥2 episodes of bradycardia, nausea, vomiting, umbilical artery and vein blood gases, and Apgar scores.
RESULTS: One hundred twelve patients were randomized. The incidence of bradycardia was lower in the NE group compared to the PE group (10.9% vs 37.5%; P < .001; difference [95% confidence interval {CI}], −26.8% [−41.8% to −11.7%]), implying an estimated 71% relative reduction (95% CI, 35%–88%). The distribution of the number of bradycardia episodes was also different between the 2 groups (P = .007). Further testing showed that the patients in the PE group had a higher risk of multiple bradycardia episodes (≥2 episodes) compared to the NE group (19.6% for PE versus 3.6% for NE; P = .008). The proportion of patients requiring rescue boluses of ephedrine was lower in the NE group compared to the PE group (7.2% for NE versus 21.4% for PE; P < .03; difference [95% CI], −14.3% [−27.0% to −1.6%]). No differences were observed between the 2 groups in the incidence of other secondary outcomes.
CONCLUSIONS: When used as an intermittent bolus regimen to prevent and treat spinal-induced hypotension during CD, NE resulted in a significant reduction in the incidence of bradycardia as compared to an equipotent bolus regimen of PE. We conclude that the hemodynamic profile offered by NE during CD is superior to that of PE due to less fluctuations in HR and possibly cardiac output.
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