|Year : 2022 | Volume
| Issue : 2 | Page : 122-126
Comparison of phenylephrine and norepinephrine for prevention of hypotension in patients undergoing cesarean section under spinal anesthesia – A randomized prospective study
Wakhloo Renu, Bhagat Heena, Gandotra Megha, Suri Era
Department of Anesthesia and Critical Care, Government Medical College, Bakshi Nagar, Jammu, India
|Date of Submission||11-Jun-2021|
|Date of Acceptance||11-Apr-2022|
|Date of Web Publication||02-Sep-2022|
Dr. Gandotra Megha
Department of Anesthesia and Critical Care, IInd Floor, Govt. Medical College, Bakshi Nagar, Jammu - 180 005
Source of Support: None, Conflict of Interest: None
Background: Hypotension is a common side effect of spinal anesthesia for cesarean section with incidence of upto 71%. Various vasopressors are available for counteracting spinal hypotension each with different pharmacological profile. Norepinephrine is currently one of the feasible options for prophylaxis of spinal induced hypotension in patients undergoing cesarean section. Aims: To compare efficacy of phenylephrine and norepinephrine for reducing incidence of hypotension in patients undergoing cesarean section under spinal anesthesia and their effect on neonatal outcome. The primary outcome compared was incidence of hypotension (defined as fall in systolic blood pressure of >20% from the baseline value or a value <90 mmHg). The secondary outcomes noted were incidence of bradycardia, nausea, vomiting in the mother, and neonatal outcome. Methodology: A total of 80 singleton full term pregnant patients of American Society of Anesthesiology (ASA) grade II scheduled for elective cesarean section were randomly assigned to 2 groups of 40 patients each. Group P received phenylephrine 50 mcg and Group N received norepinephrine 10 mcg as intravenous bolus over 1 min immediately after the patient had been made supine after giving spinal anesthesia. The vital parameters, adverse effects, and neonatal outcome were assessed and analyzed statistically. Results: Intraoperatively, norepinephrine group had a significantly higher mean heart rate than phenylephrine group. Neonatal outcome was similar in both the groups with respect to appearance, pulse, grimace, activity, and respiration (Apgar) scores and umbilical arterial pH. Conclusions: In cesarean section under spinal anesthesia, norepinephrine efficacy in rescuing maternal hypotension is similar to that of phenylephrine without obvious maternal or neonatal adverse outcomes and with a lower incidence of bradycardia.
Keywords: Hypotension, norepinephrine, phenylephrine, spinal anesthesia
|How to cite this article:|
Renu W, Heena B, Megha G, Era S. Comparison of phenylephrine and norepinephrine for prevention of hypotension in patients undergoing cesarean section under spinal anesthesia – A randomized prospective study. J Obstet Anaesth Crit Care 2022;12:122-6
|How to cite this URL:|
Renu W, Heena B, Megha G, Era S. Comparison of phenylephrine and norepinephrine for prevention of hypotension in patients undergoing cesarean section under spinal anesthesia – A randomized prospective study. J Obstet Anaesth Crit Care [serial online] 2022 [cited 2022 Oct 3];12:122-6. Available from: https://www.joacc.com/text.asp?2022/12/2/122/355347
| Introduction|| |
Maternal hypotension is the most common complication of neuraxial anesthesia in obstetric patients which occur in about 30–90% of cases. Hypotension after spinal anesthesia mainly occurs due to sympathetic blockade leading to peripheral vasodilatation and venous pooling of blood. As a result, there is decreased venous return and cardiac output leading to hypotension. When severe and sustained hypotension can impair uterine and intervillous blood flow and ultimately result in fetal acidosis and neonatal depression. Thus, the effective prevention and treatment of maternal hypotension is of great clinical significance. Phenylephrine is effective for preventing hypotension during cesarean deliveries after spinal anesthesia and does not exert an adverse effect on the fetus., Since phenylephrine use can cause severe bradycardia, norepinephrine has been studied recently as a possible alternative to phenylephrine. The use of norepinephrine is still in the experimental stage, but the results so far suggest that it could be a good alternative to currently used vasopressors, especially to avoid bradycardia, also it is a vasopressor with minimal cardiac depressant effects. The current study was conducted with the aim to study the effect of intravenous phenylephrine and norepinephrine on hemodynamics during spinal anesthesia in cesarean section and to determine the effect of study drugs on neonatal appearance, pulse, grimace, activity, and respiration (Apgar) score and acid–base analysis of neonatal blood.
| Methodology|| |
After approval from the Ethical Committee of Institute and after obtaining informed written consent, the present study was conducted on 80 singlet full term pregnant patients of ASA grade II, age 20–35 years, height (150–170 cm), weight (60–80 kg), scheduled for elective cesarean section under spinal anesthesia.
- Onset of labor
- Known fetal abnormality
- Any contraindications to spinal anesthesia
- Hypertension/pregnancy induced hypertension (PIH) (BP >140/90)
- Allergy to any study drug
- Any other medical or surgical conditions.
All patients were subjected to a detailed general physical examination as well as systemic examination. Routine investigations like hemogram, total blood counts, coagulation profile, blood sugar level, electrocardiogram (ECG), and other specific investigation as deemed necessary for the patient was undertaken. Each patient received injection pantoprazole 40 mg IV and injection metoclopramide 10 mg IV 30 min before anesthesia. In the operating room, all routine monitors like ECG, non-invasive blood pressure (NIBP), pulse-oximeter were attached and baseline values were noted. Spinal anesthesia was given L2–L3 or L3–L4 space in sitting position using 25G Quincke needle 12.5 mg of 0.5% hyperbaric bupivacaine. Simultaneously co-loading was started with ringer's lactate solution 15 mL/kg. Oxygen was administered at a rate of 5–6 L/min by venti-mask to all patients till the delivery of the baby. The study drugs were given as intravenous bolus as per group allocation immediately after the patient had been made supine following subarachnoid block.
Sensory block was assessed by loss of sensation to pin prick and motor block was assessed by Modified Bromage scale.
Time of onset of sensory level was defined as interval between intrathecal administration of drug and time to achieve block to height T6. Time to achieve motor level was defined as time when modified Bromage scale 3 achieved. Heart rate, blood pressure, and oxygen saturation were recorded immediately after spinal anesthesia, then at every minute till delivery of the baby, then every 5 min for the next 10 min, and thereafter every 10 min till the end of the surgery.
Allocation of the 2 groups was randomly done by an investigator not directly linked to the study using a table of random numbers for an even distribution of 40 patients to each of the 2 groups.
Group P: Pregnant females co-loaded with crystalloid received intravenous bolus phenylephrine 50 mcg.
Group N: Pregnant females co-loaded with crystalloid received intravenous bolus norepinephrine 10 mcg.
All solutions in both the groups were diluted with saline to a total volume of 10 mL.
Intravenous Atropine 0.3 mg was given for bradycardia (heart rate <60 bpm). Any time the patient developed hypotension (fall in systolic blood pressure >20% from the baseline value or a value <90 mmHg) injection Mephentermine 3 mg intravenous bolus was given as a rescue vasopressor. Pediatrician assessed Apgar score of every neonate at 1 and 5 min after delivery. Umbilical cord blood samples were taken for acid–base analysis of the neonate.
The following parameters were noted:
- Hemodynamic parameters of the mother.
- Apgar score of the newborn at 1 and 5 min.
- Acid–base analysis of neonate blood.
- Any adverse events (nausea, vomiting, bradycardia).
At the end of the surgery, all data were compiled and analyzed statistically. The data were entered in MS EXCEL spreadsheet and analysis was done using the Statistical Package for Social Sciences (SPSS) version 21.0. Categorical variables was presented in number and percentage (%) and continuous variables was presented as mean ± SD and median. Normality of data was tested by Kolmogorov–Smirnov test. If the normality is rejected then non parametric test was used. Statistical tests were applied as follows:
- Quantitative variables were compared using unpaired t-test/Mann–Whitney test (when the data sets were not normally distributed) between the two groups.
- Qualitative variable was compared using Chi-square test/Fisher's exact test. A P value of <0.05 was considered statistically significant.
| Results|| |
The patient flow diagram is illustrated in [Figure 1]. Eighty patients were enrolled in the study and none was excluded. There were 40 patients included in the phenylephrine group and 40 patients included in the norephinephrine group.
In our study both the groups were comparable in demographics, that is, age, weight, height with no statistical significant difference [Table 1], [Table 2], [Table 3]. The mean age in group P was 25.1 ± 2.55 years and in group N was 25.4 ± 2.87 years. The mean weight in group P was 70.9 ± 3.68 kg and in group N was 69.8 ± 3.17 kg. The mean height of patient in group P was 155.6 ± 3.22 cm and in group N was 156.8 ± 3.34 cm.
Mean time between the start of subarachnoid injection to delivery of the baby in group P was 8.13 ± 1.09 min and in group N was 8.08 ± 1.14 min (P = 0.842). Mean duration of surgery in group P was 48.5 ± 7.53 min and in group N was 49.1 ± 6.97 min (P = 0.701).
The baseline heart rate was 97.98 ± 9.768 beats/min and 94.90 ± 8.664 beats/min in P group and N group [Table 2], respectively (P = 0.068). Both the groups were comparable in term of preoperative hemodynamic variables and the difference was statistically not significant. The difference in the intraoperative mean systolic and diastolic blood pressure.
Mean Arterial Pressure (MAP) [Figure 2] and oxygen saturation amongst the two groups were statistically not significant. Intraoperatively, norepinephrine group maintained higher mean heart rate than phenylephrine group and the difference was statistically significant at 3, 4, and 5 min, respectively (P < 0.05) [Figure 3].
|Figure 2: Intraoperative mean blood pressure in two groups. Group P: Phenylephrine, Group N: Norepinephrine|
Click here to view
|Figure 3: Comparison of intraoperative heart rate. Group P: Phenylephrine, Group N: Norepinephrine|
Click here to view
In our study, neonatal outcome was similar in two groups. The mean Apgar score in group P at 1 min was 9.90 ± 0.37 and at 5 min was 9.98 ± 0.15 [Table 3]. The mean Apgar score in group N at 1 min was 9.95 ± 0.42 and at 5 min was 9.92 ± 0.27. The mean umbilical artery pH in group P was 7.23 ± 0.01 and in group N was 7.22 ± 0.01. The neonatal umbilical artery pH values were similar in the phenylephrine group. No neonate had fetal acidosis, defined as pH <7.18.
The incidences of nausea in the Group N and Group P showed no statistically significant differences. None of the patients in both the groups had any episodes of vomiting. Three patients in group P had heart rate less than 60 beats/min and needed injection atropine 0.3 mg administration while no patient in group N reported bradycardia [Table 4]. The incidence of bradycardia during caesarean section under spinal anesthesia in Group P was 7.5% and in Group N was 0%.
The two group were comparable in terms of requirement of rescue drug (inj. Mephentermine 3 mg iv bolus) [Table 5]. Number of patients who required rescue drug for hypotension was two in group P and both the patients received only one rescue dose each. Number of patients requiring rescue drug was three in group N and each patient received only one rescue dose (P-value 0.644). The incidence of hypotension in group P was 5% and in Group N was 7.5%.
| Discussion|| |
Spinal block results in a number of physiological changes in the cardiovascular system, all of which contribute to associated hypotension. Essentially all the cardiovascular effects of spinal anesthesia are mediated by preganglionic sympathetic nerve blockade. A number of measures for the prevention and treatment of spinal block-induced hypotension are used in clinical practice, such as co-loading with crystalloid and/or colloid infusion, wrapping of lower limbs with compression stockings or bandages, administering an optimal dose of local anaesthetic and achieving an optimal spinal block level, left tilt positioning, and administering inotropes and vasopressors.
The current study was conducted with the aim to compare the effectiveness of phenylephrine and norepinephrine in controlling hypotension following spinal anesthesia in 80 singlet full term pregnant patients of ASA grade II, age 20–35 years, height (150–170 cm), and weight (60–80 kg) scheduled for elective caesarean section. Baseline demographics were statistically insignificant in two groups. In our study, in intraoperatively, norepinephrine group maintained higher mean heart rate than phenylephrine group and the difference was statistically significant at 3, 4 and 5 min (P < 0.05). The result of our study were in accordance with those of Dong et al. who also observed a significant higher heart rate at 2 and 4 min after spinal anesthesia in the norepinephrine group (P < 0.05). Sharkey et al. also showed that the incidence of bradycardia was lower in the NE group compared to the PE group (10.7% vs 37.5%; P <.001).
In our study, neonatal outcome was similar in two groups. The mean Apgar score at 1 and 5 min were >7 in both the groups with a statistically non-significant difference between two groups. The mean umbilical artery pH in group P was 7.23 ± 0.013 and in group N was 7.22 ± 0.012. The neonatal umbilical artery pH values were similar in two groups, the difference being statistically non-significant. Similar results were found in study conducted by Vallejo et al. showed that there were no differences between groups in the proportion of Apgar scores at 1 and 5 min, or in umbilical venous cord blood gases. Our result also matches with that of Ngan Kee et al. showed that neonatal outcome was similar between groups.
All Apgar scores at 1 and 5 min were >7, and no patient had umbilical artery pH <7.2. Sharkey et al. showed that the Apgar scores at 1 and 5 min were >7 in all cases, with no differences were seen in umbilical cord blood gases between the two groups. Side effects like nausea, vomiting, and bradycardia have been variably reported during spinal anesthesia or with the use of vasopressor drugs [Table 4]. The incidences of nausea in the Group N and Group P showed no statistically significant differences. None of the patients in both the groups had any episodes of vomiting. The incidence of bradycardia (defined as heart rate <60 beats/min) was 7.5% in phenylephrine group and 0% in norepinephrine group but the difference was statistically non-significant (P = 0.241). The result were in accordance with that of Thomas et al. who also found a significant reduction in heart rate in the phenylephrine group. Ngan Kee et al. also showed that heart rate was greater in the norepinephrine group compared with that in the phenylephrine group (P = 0.36).
The two group were comparable in terms of requirement of rescue drug (inj. Mephentermine 3 mg) with P value 0.644. A similar study done by Dong et al. in which the rescue vasopressor required in phenylephrine group was 8% and in norepinephrine group was 5% (P-value = 0.5). Vallejo et al. also showed that there was no difference between groups in the proportion of patients who required rescue vasopressor boluses (Group P: 65.8% vs. Group N 48.8%, P = 0.12).
| Conclusion|| |
From our study, we concluded that when phenylephrine 50 mcg and norepinephrine 10 mcg intravenously are used to maintain arterial blood pressure during spinal anesthesia in caesarean section, norephinehrine efficacy in rescuing maternal hypotension is similar to that of phenylephrine without obvious maternal or neonatal adverse outcomes and with a lower incidence of bradycardia. Accordingly, norepinephrine is a promising alternative to phenylephrine.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Räsänen J, Alahuhta S, Kangas-Saarela T, Jouppila R, Jouppila P. The effect of ephedrine and etilefrine on uterine and fetal blood flow and on fetal myocardial function during spinal anaesthesia for caesarean section. Int J Obstet Anesth 1991;1:3-8.
Ueyama H, He YL, Tanigami H, Mashimo T, Yoshiya I. Effects of crystalloid and colloid preload on blood volume in the parturient undergoing spinal anesthesia for elective cesarean section. Anesthesiology 1999;91:1571-6.
Loughrey JPR, Yao N, Datta S, Segal S, Pian-Smith M, Tsen LC. Hemodynamic effects of spinal anesthesia and simultaneously intravenous bolus of combined phenylephrine and ephedrine versus ephedrine for caesarean delivery. Int J Obstet Anesth 2005;14:43-7.
Cyna AM, Andrew M, Emmett RS, Middleton P, Simmons SW. Techniques for preventing hypotension during spinal anaesthesia for caesarean section. Cochrane Database Syst Rev 2006:CD002251. doi: 10.1002/14651858.CD002251.pub2.
Reidy J, Douglas J. Vasopressors in obstetrics. Anesthesiol Clin 2008;26:75-88.
Ngan Kee WD, Lee SWY, Ng FF, Khaw KS. Prophylactic norepinephrine infusion for preventing hypotension during spinal anesthesia for caesarean delivery. Anesth Analg 2018;126:1989-94.
Wang X, Shen X, Liu S, Yang J, Xu S. The efficacy and safety of norepinephrine and its feasibility as a replacement for phenylephrine to manage maternal hypotension during elective cesarean delivery under spinal anesthesia. Biomed Res Int 2018;2018:1869189.
Dong L, Dong Q, Song X, Liu Y, Wang Y. Comparision of prophylactic bolus norepinephrine and phenylephrine on hypotension during spinal anesthesia for caesarean section. Int J Clin Exp Med 2017;10:12315-21.
Sharkey AM, Siddiqui N, Downey K, Ye XY, Guevara J, Carvalho JCA. Comparison of intermittent intravenous boluses of phenylephrine and norepinephrine to prevent and treat spinal-induced hypotension in caesarean deliveries: Randomised controlled trial. Anesth Analg 2019;129:1312-8.
Vallejo MC, Attaallah AF, Elzamzamy OM, Cifarelli DT, Phelps AL, Hobbs GR, et al
. An open-label randomized controlled clinical trial for comparison of continuous phenylephrine versus norepinephrine infusion in prevention of spinal hypotension during caesarean delivery. Int J Obstet Anesth 2017;29:18-25.
Ngan Kee WD, Lee SWY, Ng FF, Tan PE, Khaw KS. Randomized double- blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery. Anesthesiology 2015;122:736-45.
Thomas DG, Robson SC, Redfern N, Hughes D, Boys RJ. Randomized trial of bolus phenylephrine or ephedrine for maintenance of arterial pressure during spinal anaesthesia for caesarean section. Br J Anesth 1996;76:61-5.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]