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Original Article Comparison of Prophylactic Bolus Norepinephrine and Phenylephrine on Hypotension During Spinal Anesthesia for Cesarean Section

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Original Article Comparison of Prophylactic Bolus Norepinephrine and Phenylephrine on Hypotension During Spinal Anesthesia for Cesarean Section Int J Clin Exp Med 2017;10(8):12315-12321 www.ijcem.com /ISSN:1940-5901/IJCEM0057154 Original Article Comparison of prophylactic bolus norepinephrine and phenylephrine on hypotension during spinal anesthesia for cesarean section Ling Dong1, Qian Dong2, Xiumei Song1, Yang Liu1, Yuelan Wang1 1Department of Anesthesiology, Qianfoshan Hospital, Shandong University, Jinan, Shandong, China; 2Department of Marketing, Qilu Clinical Laboratory Company, Jinan, Shandong, China Received May 10, 2017; Accepted July 21, 2017; Epub August 15, 2017; Published August 30, 2017 Abstract: Background and objective: Phenylephrine is the first-line choice for prevention and treatment of hypoten- sion during spinal anesthesia for cesarean section. However, the serious bradycardia caused by phenylephrine is a concern. This study compared the effects of prophylactic bolus norepinephrine and phenylephrine on hypotension during spinal anesthesia for cesarean section. Methods: A total of 132 healthy parturients having cesarean section under spinal anesthesia were enrolled in this prospective, randomized, double-blinded, parallel-group trial. Patients were randomized to receive prophylactic bolus norepinephrine (10 μg) or phenylephrine (50 μg) immediately after spinal anesthesia. The primary outcome compared was incidence of bradycardia (defined as heart rate < 60 beats/ min). The secondary outcomes were blood pressure, heart rate, cardiac output, nausea and vomiting, and neonatal outcome. Results: The incidence of bradycardia was significantly lower in the norepinephrine group (2%) than that in the phenylephrine group (13%, P < 0.05). Five patients had heart rate lower than 55 beats/min and needed atropine 0.5 mg administration in the phenylephrine group. Cardiac output at 5 min was significantly greater in the norepinephrine group than that in the phenylephrine group (P < 0.05). From induction until delivery, there were no significant differences in systolic blood pressure. Neonatal outcome was similar between groups. Conclusions: Norepinephrine is as effective as phenylephrine in preventing spinal hypotension but has less adverse effects on heart rate and greater cardiac output than phenylephrine during caesarean section. Keywords: Spinal anesthesia, cesarean section, norepinephrine, phenylephrine, hypotension Introduction that might be beneficial to counteract pure vasoconstriction [4]. In our routine practice, we Hypotension is a common side effect of spinal have observed that norepinephrine was associ- anesthesia for cesarean section, with an inci- ated with a lower incidence of bradycardia than dence of up to 71% [1]. Currently, phenyleph- phenylephrine. We postulate that norepineph- rine is the first-line choice for prevention of rine might therefore be a more effective vaso- hypotension during spinal anesthesia for cesar- pressor for preventing and maintaining blood ean section [2]. However, the serious bradycar- pressure during spinal anesthesia. dia caused by phenylephrine is a concern and it requires atropine treatment [3]. Furthermore, The primary aim of this randomized, double- phenylephrine is ineffective in some patients blinded study is to compare the effects of pro- and thus other vasopressor agents are phylactic bolus norepinephrine and phenyleph- needed. rine on hypotension during spinal anesthesia for cesarean section. The adverse effects and Norepinephrine, like phenylephrine, also has effects on heart rate and cardiac output were α-adrenergic properties that can be used to evaluated. We also measured Apgar scores and treat spinal anesthesia-induced vasodilatation. umbilical cord blood pH to evaluate the effect But unlike phenylephrine, norepinephrine has of these two vasopressor drugs on neonatal mild and dose-dependent β-adrenergic effects outcome. Norepinephrine vs. phenylephrine in hypotension Materials and methods (Astra Zeneca Pharmaceuticals, Sweden) was injected intrathecally. After intrathecal injec- Patient and randomization tion, an epidural catheter was inserted 5 cm into the epidural space and fixed after confirm- This prospective, randomized, double-blinded, ing the absence of cerebrospinal fluid or blood. parallel-group study enrolled 132 patients. No drug was injected into the epidural catheter Patients were evaluated at the day before sur- at this time. At the start of intrathecal injection, gery by an anesthesiologist. The inclusion crite- 10 mL/kg of Ringer’s lactate solution was per- ria were: ASA (American Society of Anesth- formed rapidly. esiologists) physical status 1 to 2, singleton term pregnancy, and scheduled for elective After the block, the patient was placed in the cesarean section under spinal anesthesia. supine position with standard left lateral tilt Exclusion criteria were: age less than 18 year, until delivery of the baby. Success of spinal height less than 150 cm or more than 180 cm, anesthesia was defined as a bilateral T6 sen- weight less than 50 kg or more than 100 kg, sory level to pinprick within 10 min of intrathe- contraindications to spinal anesthesia, allergy cal injection. The failure of spinal anesthesia to drugs used in the study, preeclampsia, pla- was recorded when a T6 sensory level was not centa praevia, diabetes mellitus, hypertension, obtained within 10 min. Patients with failure of or cardiovascular disease. Approval for this spinal anesthesia were excluded from the study was obtained from the Ethic committee study. If the failure was recorded, 5 ml incre- of Qianfoshan Hospital, Shandong University, ments of 2% lidocaine were administered Shandong, China. Written informed consent through the epidural catheter every 5 min until was obtained from all subjects. block height attained T6 level. Baseline measurement Prophylactic bolus treatment and patient grouping Patients were fasted for at least 8 hours and had no premedication. Patients were in the When spinal anesthesia was finished, all the supine position with left lateral tilt on the oper- patients were randomized into norepinephrine ating table, and they were monitored by electro- group and phenylephrine group. Patients in the cardiogram, automated noninvasive arterial norepinephrine group received an i.v. bolus of blood pressure monitors, and pulse oximetry. norepinephrine 10 μg (10 μg/ml) and those in An 18-gauge intravenous cannula connected to the phenylephrine group received an i.v. bolus a three-way stopcock was placed in a forearm of phenylephrine 50 μg (50 μg/ml). All the drugs vein, but no prehydration. Baseline arterial were prepared by dilution in 5% dextrose solu- blood pressure was defined as the mean of tion. Randomization was performed according three consecutive readings at 1-minute inter- to computer-generated codes contained in op- vals with differences less than 10%. The mean aque, sealed and sequentially-numbered enve- heart rates (HR) at these times were defined as lopes. The anesthesiologist, patients, operator baseline HRs. Baseline cardiac output (CO) was and midwives involved in the study were blind- defined as mean of three noninvasive supra- ed to the patient grouping. The doses of phenyl- sternal Doppler measurements. The mean val- ephrine and norepinephrine were chosen ues of three measurements were defined as empirically, based on our clinical experience. the baseline value. All measurements were made by the same experienced operator who Measurements and outcomes was blinded to group assignment. The noninvasive blood pressure and HR were Spinal-epidural anesthesia measured at 1 min intervals and the CO level was measured at 5 min intervals until delivery All the patients underwent a combined spinal- from the time of finishing intrathecal injection. epidural anesthesia using a needle-through- The incidences of hypotension (defined as sys- needle set in the right lateral position at the tolic blood pressure (SBP) < 80% of baseline), estimated L2-L3 or L3-L4 vertebral interspace. hypertension (defined as SBP > 120% of base- When free-flowing cerebrospinal fluid was line), bradycardia (defined as HR < 60 beats/ observed, 0.5% isobaric ropivacaine (15 mg) min), nausea and vomiting were recorded. 12316 Int J Clin Exp Med 2017;10(8):12315-12321 Norepinephrine vs. phenylephrine in hypotension as mean values ± standard deviation (SD) and non-pa- Figure 1. CONSORT statement rametric data as medians participant flow chart. (range), as appropriate. Uni- variate intergroup compari- sons were conducted using the unpaired Student t test or the Mann-Whitney U test. Nominal data were com- pared using the chi-square test or the Fisher exact test. P values < 0.05 were consid- ered statistically significant. Results Patient characteristics Table 1. Patient characteristics and time The patient flow diagram is illustrated in Figure Norepinephrine Phenylephrine 1. One hundred and thirty-two patients were group (n = 62) group (n = 64) enrolled in the study. Six were excluded due to Age, yr 31.5 (3.5) 30.5 (4.9) failure of spinal anesthesia. Finally, there were 62 patients included in the norepinephrine Weight, kg 72.6 (8.1) 75.3 (8.3) group and 64 patients included in the phenyl- Height, cm 157 (6.7) 158 (8.2) ephrine group. Patient characteristics and sur- Block height T6 (T4-7) T5 (T3-6) gical times are shown in Table 1. There was no Spinal-delivery, min 22 (17-28) 19 (16-25) difference between groups in patient charac- Incision-delivery, min 11 (8-13) 9 (7-10) teristics and surgical times. UI-delivery, s 8 (60-119) 94 (63-125) Values are means (standard deviation) or medians (inter- Effects of norepinephrine
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