|Year : 2020 | Volume
| Issue : 2 | Page : 118-122
Clinical comparison of prophylactic phenylephrine infusion vs. bolus regimens on maternal hemodynamics and neonatal outcomes during cesarean section
Nitesh Kumar1, Mathews Jacob1, Priya Taank2, Shalendra Singh1, Neetika Tripathi1
1 Department of Anaesthesiology and Critical Care, Armed Forces Medical College, Pune, Maharashtra, India
2 Department of Ophthalmology, CH (SC), Pune, Maharashtra, India
|Date of Submission||22-May-2020|
|Date of Acceptance||12-Jul-2020|
|Date of Web Publication||20-Aug-2020|
Dr. Shalendra Singh
Department of Anaesthesiology and Critical Care, Armed Forces Medical College, Pune - 411 040, Maharashtra
Source of Support: None, Conflict of Interest: None
Background and Objective: Phenylephrine bolus or infusion is used to maintain arterial blood pressure during the subarachnoid block (SAB) for cesarean section. The objective was to assess the clinical efficacy of prophylactic phenylephrine infusion or bolus doses for maternal hemodynamics maintenance and its effect on fetal outcomes. Materials and Methods: Sixty parturients were randomized to receive either a continuous prophylactic IV infusion of phenylephrine (n = 30, group A) at a dose of 0.50 μg.kg−1.min−1 or phenylephrine (n = 30, Group B) 50 μg bolus dose after the systolic blood pressure (SBP) fell by 20% from the baseline. The changes in hemodynamics, ill effects, neonatal APGAR scores, and fetal acidosis were recorded at different time intervals. Results: SBP was significantly higher over time in group A. Group A showed a significant fall in heart rate from baseline after giving SAB and remained significantly low throughout the intraoperative period (P < 0.05). In group A, 12 patients showed a fall in blood pressure of >20% from the baseline; however, hypotension was observed in 21 patients in group B (P < 0.03). The number of hypotensive episodes was higher in the group B. Incidence of hypotension in Group A was 40% (12 out of 30 patients) and 70% (21 out of 30 patients) in Group B (P < 0.037). Episodes of reactive hypertension, defined as a rise in SBP >20% of baseline value, were noted in 3 out of 30 patients in the Group A. There was also a statistically nonsignificant trend toward a less frequent incidence of nausea and vomiting in the group A (P < 0.29). There was no significant difference between the two groups in APGAR scores at 1 and 5 min after delivery (P < 0.56, 0.13). The incidence of neonatal acidosis was similar in the two groups. Conclusion: Prophylactic phenylephrine infusion is superior to therapeutic phenylephrine bolus dose for control of hemodynamics.
Keywords: APGAR, cesarean section, neonatal outcome, phenylephrine, subarachnoid block, umbilical arterial blood
|How to cite this article:|
Kumar N, Jacob M, Taank P, Singh S, Tripathi N. Clinical comparison of prophylactic phenylephrine infusion vs. bolus regimens on maternal hemodynamics and neonatal outcomes during cesarean section. J Obstet Anaesth Crit Care 2020;10:118-22
|How to cite this URL:|
Kumar N, Jacob M, Taank P, Singh S, Tripathi N. Clinical comparison of prophylactic phenylephrine infusion vs. bolus regimens on maternal hemodynamics and neonatal outcomes during cesarean section. J Obstet Anaesth Crit Care [serial online] 2020 [cited 2020 Dec 2];10:118-22. Available from: https://www.joacc.com/text.asp?2020/10/2/118/292741
| Introduction|| |
The most acceptable anesthetic technique for elective cesarean section (CS) deliveries is the subarachnoid block (SAB), as general anesthesia (GA) encounters multiple airway issues. But, it is associated with hypotension in 70-80% cases, irrespective of preloading/coloading, when pharmacological prophylaxis is not used. Hypotension can have detrimental effects on both the mother and the neonate. It causes nausea-vomiting and dizziness in mother and uteroplacental hypoperfusion in neonate results in fetal acidosis., Therefore, prevention and treatment of hypotension with left lateral tilt, judicious use of vasopressor/fluid regimen for optimal control of maternal blood pressure (BP), and fetal circulation are an essential issue for anesthesiologists.
A Cochrane review in the year 2017 revealed that no single drug or technique is proven to prevent SAB-induced maternal hypotension. Literature previously recommended ephedrine as a drug of choice for SAB-induced hypotension, but concerns of ephedrine-induced supraventricular tachycardia, tachyphylaxis, and fetal acidosis limited its use subsequently. Contemporary articles emphasize phenylephrine as a drug of choice. However, the American Society of Anesthesiologists Task Force Guidelines recommends the use of any vasopressor except in the presence of maternal bradycardia where phenylephrine is contraindicated.
Phenylephrine (a strong α-agonist of sympathetic receptors) is effective as a vasopressor in the management of hypotension. It decreases complications like nausea and vomiting and fetal acidosis, but it may increase the incidence of maternal bradycardia. Therefore, the use of phenylephrine, especially for prophylaxis of hypotension, is uncommon.,,
The present practice is to react to hypotension by giving phenylephrine bolus as a therapeutic intervention. However, recent studies indicate that prophylactic administration of phenylephrine, especially as an infusion, is better in controlling BP after SAB in elective CS., Scant studies are available in Indian settings regarding the use of prophylactic phenylephrine infusions and their efficacy. The primary objective is to assess and compare the efficacy of prophylactic phenylephrine infusion vs. therapeutic phenylephrine bolus dose on maternal hemodynamics and fetal outcome. The secondary aim was to study maternal nausea and vomiting, neonatal outcome, and side effects with the two regimens.
| Materials and Methods|| |
This observational study was carried out at a tertiary level hospital in India. It was conducted after approval from the institutional ethics committee and written informed consent was obtained from the patients. A total of 60 patients in American society of anaesthesiology (ASA) physical status I or II, with uncomplicated singleton pregnancy without known fetal abnormalities undergoing elective CS requiring SAB, were enrolled for this study. Patients with known allergy/hypersensitivity to the study drug, younger than 18 years of age, bleeding disorder, hypertensive illness, gestational age <36 weeks, psychiatric illness, heart failure, and poor English comprehension were excluded from the study.
Patients were placed in the dorsal decubitus position dislocating the uterus to the left for a few minutes. Baseline three consecutive readings of BP and Heart rate (HR) at an interval of 1 min were recorded. Coloading with normal saline was started totaling to 10 mL/kg. With the patient in the sitting position, SAB was performed with a 25 G Quincke needle in the L3-L4 space, and a solution containing 2.0 mL of hyperbaric 0.5% bupivacaine and 15 μg of fentanyl was administered. Post administration of the drug, the patient was made supine and a wedge of 15 cm placed under the right buttock immediately. During the study period using consecutive sampling, initial 30 patients fulfilling study protocol were given prophylactic phenylephrine infusion (group A), and the next 30 patients were given therapeutic bolus phenylephrine dose (group B). Hemodynamics were measured at 1-min intervals beginning immediately after SAB till delivery of the baby. In group A, continuous intravenous infusion of phenylephrine at 0.5 μg/kg/min was started immediately after the administration of SAB and maintained till the delivery of the baby and stopped if systolic blood pressure (SBP) rises to more than 20% the baseline, which will be referred to as reactive hypertension. In Group B, a bolus dose of phenylephrine 50 μg was given in case of a fall in SBP of >20% of mean baseline values. Rescue dose of 30 μg of phenylephrine was given as a bolus and repeated every 2 min, in case of a drop in SBP greater than 20%, not controlled with the therapeutic/prophylactic regimens in both the groups. Episodes of hypotension defined as a drop in SBP greater than 20% were recorded. Bradycardia was defined as ≥20 % decrease in HR from the baseline value and was treated if associated with hypotension or HR below 45 beats/min, with intravenous glycopyrrolate. Nausea, vomiting, and the need for rescue doses of phenylephrine were recorded. As soon as the fetus was delivered, the infusion was stopped, and the total dose of vasopressor was noted in both the groups. Umbilical arterial blood samples from a segment of the clamped umbilical cord were obtained and analyzed using a blood gas analyzer. APGAR scores at 1 and 5 min were noted.
The data were analyzed using Statistical Package for Social Sciences (SPSS version 20.0) (SPSS, Inc, Chicago IL, USA). The sample size of 30 was calculated in each group with an alpha error of 5% and power of study taken as 80% based on the previous study. Chi-square test was used to identify differences in the incidence of hypotension, fetal acidosis, APGAR scores at 1 and 5 min, and test the difference in incidences of nausea/vomiting among the two groups. Unpaired t-test was used to compare variables such as age, the weight of patients, baseline SBP, baseline diastolic blood pressure (DBP) and HR, umbilical arterial pH, and APGAR scores at various time intervals. A P value of less than 0.05 was considered statistically significant.
| Results|| |
Evaluation of comparison between therapeutic and bolus dose of phenylephrine under SAB in CS patients was studied from Jan 2016 to Feb 2017. Out of a total of 168 patients listed for surgery during the study period, 98 patients did not meet inclusion criteria, and 06 patients were not included due to refusal, and 04 cases were converted to GA after SAB failed. Demographic parameters and hemodynamic characteristics were comparable between the groups [Table 1]. The total IV fluids administered were comparable in both groups (1655 ± 275.3 mL in group A vs. 1555 ± 275.3 mL in group B, P < 0.12).
|Table 1: Demographic profile and baseline hemodynamic characteristics of patients in both the groups|
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The baseline hemodynamics SBP, DBP, and pulse oximetry were normal and comparable in both the groups [Table 1]. The maximum SBP recorded was greater in group A. There is a significant difference between mean SBP at 1 min to 10 min except at baseline. There is a significant difference between mean DBP at each time interval after SAB except at the time interval at 6 min. SBP was significantly greater over time in group A compared with group B [Table 2] and that HR significantly decreased over time in group A as compared to group B. The group A showed a significant fall in HR from baseline after giving SAB and remained significantly low throughout the intraoperative period (P < 0.05) [Table 2]. The number of hypotensive episodes was higher in Group B as compared to the Group A. Nine episodes of hypotension (BP <20% during monitoring time) were observed in 02 patients in group A and 01 patient in group B. Incidence of maternal hypotension in Group A was 40% (12 out of 30 patients) and 70% (21 out of 30 patients) in Group B (P-value <0.03). Episodes of reactive hypertension, defined as a rise in SBP >20% of baseline value, were noted in 3 out of 30 patients in the Group A. None of the patients of Group B had reactive hypertension [Table 3].
|Table 2: Systemic hemodynamic parameters (values expressed as mean±SD or number) during 10 min observation period in two groups|
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|Table 3: Incidence of nausea and vomiting, APGAR score, neonatal acidosis, and the episode of hypotension|
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Also, the patients who developed reactive hypertension did not complain of any symptoms nor required treatment of any form.
There was also a statistically nonsignificant trend toward a less frequent incidence of nausea and vomiting in the infusion group compared with the bolus group, i.e., 3 (10%) in group A vs. 7 (23%) in group B (P < 0.29). There was no significant difference between the two groups when the neonatal outcomes were compared. APGAR scores at 1 and 5 min after delivery were compared between the two groups, and the difference was statistically insignificant with P = 0.56 and 0.13, respectively. The incidence of neonatal acidosis, as depicted by neonatal umbilical arterial blood pH was similar in the two groups [Table 3].
| Discussion|| |
Phenylephrine was used in our study because it is considered the first drug of choice, and its efficacy and safety during elective CS have been thoroughly investigated in various studies.
The dose being used in our study was 0.5 μg/kg/min. Ngan Kee et al., in their study published in 2004, used a dose of 100 μg/min prophylactic infusion of phenylephrine and concluded that the incidence of reactive hypertension is 38%. It consequently led to large cumulative doses of phenylephrine as compared to the rescue dose group. Lee et al. and Kuhn et al. used a prophylactic bolus dose of 1.5 μg/kg and 0.25 μg/kg/min infusion rate, respectively, and concluded that it is enough to prevent hypotension., Therefore, using a weight-based dosing regimen of 0.5 μg/kg/min was imperative to prevent both hypotension and reactive hypertension.
We compared prophylactic infusion because it offers the advantage of reduced incidence of maternal hypotension prior to delivery of the fetus and thus less uteroplacental insufficiency.
Most of the recent studies concluded that prophylactic IV phenylephrine infusion had a better outcome in controlling the hemodynamics of parturients scheduled for elective CS under SAB. Ngan Kee et al. concluded in their study that prophylactic phenylephrine is effective at reducing maternal hypotension after SAB for elective CS. das Neves et al. concluded through their study that continuous prophylactic infusion of phenylephrine initiated immediately after the SAB for CS is more effective in reducing the incidence of hypotension and maternal and fetal side effects. Despite the occurrence of hypotension in the bolus group, the fetal acid-base status remained similar compared to the infusion group. This probably shows that the episodes of hypotension were promptly treated with phenylephrine bolus.
The study demonstrated that starting a prophylactic infusion of phenylephrine immediately after induction of SAB for elective CS effectively reduced the overall incidence, frequency, and severity of maternal hypotension. Despite the use of a high dose of phenylephrine in the infusion group, the fetal acid-base status and APGAR scores were similar to those in the therapeutic bolus group. This disproves the fact that pure alpha-agonists may cause impaired uteroplacental circulation. No direct assessment of uteroplacental flow or resistance was done; however, the high values for umbilical arterial pH in our study are indirect evidence that there was no significant adverse effect. In spite of a greater incidence of hypotension in the bolus group, we found that fetal acid-base status was similar compared to that observed in the infusion group. This likely revealed the fact that when hypotension occurred, it was treated promptly with boluses of phenylephrine.
There was a statistically nonsignificant trend toward a lesser incidence of nausea and vomiting in the infusion group (10%) as compared to the bolus group (23.3%). This could be explained by the small sample size of our study, and it is not powered enough to determine the differences in this secondary outcome. Ngan Kee and colleagues have reported that women who had their SBP maintained near baseline values with a phenylephrine infusion had a reduced incidence of nausea or vomiting and higher umbilical artery pH values (lesser fetal acidosis) compared with patients where SBP was maintained at <100% of baseline values.
There are some limitations to our study. First, only ASA I-II healthy parturients undergoing elective CSs were studied. It may not be prudent to extrapolate the study findings to patients with nonreassuring NST, evidence of compromised uteroplacental blood flow, and preeclamptic patients. The sample size was small, 30 in each study group. Randomized controlled trials on a larger scale may give additional and more reliable conclusions. The dose used was a fixed weight-based one, and a variable titrated dose based on hemodynamics of patient seems more prudent considering bradycardia and reactive hypertension as the most common adverse effects.
| Conclusion|| |
Prophylactic phenylephrine weight-based infusion is an effective strategy to reduce the incidence and severity of maternal hypotension and maintain stable hemodynamics, and does not have any adverse neonatal effects when used immediately after administration of SAB drug for elective CS in otherwise healthy parturients. The other maternal adverse effects of hypotension, such as nausea, vomiting, and feeling of impending doom, may also be mitigated by the use of prophylactic infusion of phenylephrine but will require large-scale studies with sufficient power to substantiate this finding. Our study concluded that prophylactic phenylephrine infusion is superior to therapeutic phenylephrine bolus dose for control of BP after SAB in elective CS.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]