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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 9  |  Issue : 2  |  Page : 94-98

Effect of intravenous ondansetron on maternal hemodynamics during elective caesarean section under subarachnoid block


1 Department of Anaesthesia, Max Hospital, Mohali, Punjab, India
2 Department of Anaesthesia, DMCH, Ludhiana , Punjab, India
3 Adesh Institute of Medical Sciences and Research, Bathinda, Punjab, India

Date of Submission18-Jun-2019
Date of Acceptance09-Jul-2019
Date of Web Publication6-Sep-2019

Correspondence Address:
Dr. Namrata Sharma
Department of Anaesthesia (1st Floor), DMCH, Ludhiana - 141 001, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/joacc.JOACC_27_19

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  Abstract 


Background and Aims: The Bezold–Jarisch reflex (BJR) is considered to contribute to subarachnoid block (SAB)-induced hypotension and bradycardia and is mediated by serotonin receptors (5-HT3 subtype). Ondansetron, a 5-HT3 receptor antagonist, is assumed to block the effect of serotonin and inhibit BJR. The aim was to study the effect of intravenous ondansetron on maternal hemodynamics. Materials and Methods: The study was conducted on 150 healthy parturients scheduled for elective caesarean section under SAB who were randomly allocated into two groups of 75 each to receive either 4 mg ondansetron or 0.9% normal saline 10 min before initiation of SAB. Hemodynamic parameters were studied from the time of administration of the study drug upto the time of delivery of baby. Results: Both the groups were comparable to each other with respect to baseline hemodynamic parameters. SAB-induced fall in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) was significantly less in the ondansetron group when compared with placebo from the time of initiation of SAB upto 12 min of surgery time (P < 0.05). However, the difference in heart rate between both groups was not statistically significant. The total use of vasopressors was significantly low in ondansetron group when compared with placebo (P < 0.05). Better neonatal outcomes were observed in the ondansetron group. Conclusion: Intravenous ondansetron premedication can successfully attenuate SAB-induced fall in SBP, DBP, and MAP in parturients undergoing elective caesarean sections.

Keywords: Bezold–Jarisch reflex, caesarean section, hypotension, ondansetron, serotonin, subarachnoid block


How to cite this article:
Attri A, Sharma N, Singh MR, Bansal K, Singh S. Effect of intravenous ondansetron on maternal hemodynamics during elective caesarean section under subarachnoid block. J Obstet Anaesth Crit Care 2019;9:94-8

How to cite this URL:
Attri A, Sharma N, Singh MR, Bansal K, Singh S. Effect of intravenous ondansetron on maternal hemodynamics during elective caesarean section under subarachnoid block. J Obstet Anaesth Crit Care [serial online] 2019 [cited 2019 Nov 14];9:94-8. Available from: http://www.joacc.com/text.asp?2019/9/2/94/266144




  Introduction Top


Subarachnoid block (SAB) is the most commonly used anesthetic technique for elective caesarean sections,[1] with associated complications including hypotension and bradycardia with a reported incidence of 33% and 13%, respectively, for nonobstetric population and upto 50%–60% in obstetric population.[2] Caesarean sections require a sensory block till T4 level which leads to an extended sympathetic block involving the entire thoracolumbar outflow.[3] This leads to decrease in preload by venodilation and decrease in afterload by causing a decrease in systemic vascular resistance thus causing a fall in the mean arterial pressure (MAP).[4] This fall in MAP is exaggerated by the physiological changes in pregnancy along with compression of the vena cava by the gravid uterus.[5] The Bezold–Jarisch Reflex (BJR), a cardioinhibitory reflex mediated by serotonin receptors (5-HT3) present on the vagus nerve and within the walls of cardiac ventricles, is also known to contribute to hypotension and bradycardia induced by SAB.[6] Activation of these receptors occurs due to a sudden decrease in left ventricular volume which may be seen with hypovolemia, orthostasis, regional anesthesia, and aortocaval compression during pregnancy.[6] This leads to sudden activation of the parasympathetic system and sympathetic withdrawal causing vasodilation, bradycardia, and hypotension.[7] Ondansetron, a widely used antiemetic,[8] is a 5-HT3 antagonist that is assumed to block the effect of serotonin which can directly trigger the BJR. We hypothesize to use ondansetron prophylactically to attenuate hypotension and bradycardia after SAB in both nonobstetric and obstetric patients, thereby limiting the need for vasopressors and other modalities to maintain hemodynamic stability.[9],[10],[11]


  Materials and Methods Top


The study was conducted after approval from the Institutional ethics committee (January 2016) in a randomized double-blind method on a total of 150 parturients scheduled for elective lower segment caesarean section under SAB. A written informed consent was taken from all the patients before the procedure.

Parturients were allocated randomly into two groups: group O – parturients received 4 mg (2 mL) ondansetron diluted to 10 mL of 0.9% normal saline 10 min before administration of SAB and group P – parturients received 10 mL of 0.9% normal saline 10 min before administration of SAB.

Parturients undergoing elective lower segment caesarean section under SAB with American Society of Anesthesiologists (ASA) grade II were included in the study. Exclusion criteria included uncooperative and unwilling parturients, history of uncontrolled hypertension, gestational hypertension, pre-eclampsia, eclampsia, uncontrolled diabetes mellitus, cardiac disease, parturients with prolonged QT interval on electrocardiogram (ECG), known drug allergy to ondansetron, contraindications to neuraxial anesthesia, failed SAB, and its conversion to general anesthesia or planned general anesthesia.

The study drug was administered 10 min prior to administration of SAB. Monitoring in the form of heart rate (HR), noninvasive blood pressure, respiratory rate (RR), peripheral oxygen saturation (SpO2), and ECG was done by a blinded observer. SAB was performed with 2.2 mL bupivacaine 0.5% (hyperbaric) using 26-gauge Quincke's needle. Any significant change in hemodynamics in the post SAB period was noted. Hypotension was defined as systolic blood pressure (SBP) less than 20% of the baseline. This was considered as the threshold for treatment of hypotension. The treatment was standardized to an infusion of balanced salt solution and injection phenylephrine in boluses of 20 μg intravenously (i.v.). Any episode of intraoperative bradycardia with HR less than 50 beats/min was managed with injection atropine 0.01 mg/kg i.v. After the delivery of the baby, uterotonic drug in the form of injection oxytocin was administered as an i.v. bolus of 5 units followed by an infusion of 20 units in 500 mL normal saline over a period of 30 min. This period after the delivery of baby was excluded from the study to remove any confounding effect of uterotonic drugs on blood pressure readings.

Outcome measures

The primary outcome included BP and HR in the two groups from the time of initiation of SAB upto the time of delivery.

The secondary outcomes consisted of the total amount of fluid administered, amount of phenylephrine and atropine used, and Apgar score at 1 and 5 min.

Statistical analysis

Data were described in terms of range, mean ± standard deviation, median, frequencies (number of cases), and relative frequencies (percentages) as appropriate. Comparison of quantitative variables between the study groups was done using Student's t-test and Mann–Whitney U-test for independent samples for parametric and nonparametric data, respectively. For comparing categorical data, Chi-square (χ2) test was performed and exact test was used when the expected frequency is less than 5. A probability value (P value) less than 0.05 was considered statistically significant. All statistical calculations were done using Statistical Package for the Social Science (SPSS) version 21 statistical program for Microsoft Windows.


  Results Top


A total of 150 parturients were included in our study. None of the parturients were excluded and both the groups were statistically comparable with respect to age, weight, and ASA grade. The baseline HR, SBP, diastolic blood pressure (DBP), and MAP were comparable between both the groups [Table 1].
Table 1: Baseline hemodynamic parameters

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On intergroup comparison from the time of administration of study drug to the time of delivery of the baby, the difference in mean HR was statistically insignificant with P> 0.05 at all times during the study period [Figure 1]. Higher mean SBP recordings were observed in group O when compared with group P immediately after the administration of SAB (P < 0.05), incision time (P < 0.05), 2 min (P < 0.05), 4 min (P < 0.05), 6 min (P < 0.05), 8 min (P < 0.05), 10 min (P < 0.05), and 12 min (P < 0.05) and the difference between both the groups was statistically significant. The difference in mean SBP was insignificant at other times during the study period [Figure 2]. Higher mean DBP recordings were observed in group O at the time of administration of SAB (P < 0.05), incision time (P < 0.05), 2 min (P < 0.05), 4 min (P < 0.05), 6 min (P < 0.05), 8 min (P < 0.05), 10 min (P < 0.05), and 12 min (P < 0.05) and this difference between both the groups was statistically significant. The difference in mean DBP was insignificant at other times during the study period [Figure 3]. Observed MAP recordings were higher in group O at the time of administration of SAB (P < 0.05), incision time (P < 0.05), 2 min (P < 0.05), 4 min (P < 0.05), 6 min (P < 0.05), 8 min (P < 0.05), 10 min (P < 0.05), and 12 min (P < 0.05) and the difference between both the groups was statistically significant. The difference in MAP was insignificant at other times during the study period [Figure 4]. The mean oxygen saturation, RR, total intraoperative blood loss, and total use of atropine were comparable between both the groups. The total intraoperative fluid requirement was lower in group O when compared with group P and the difference was statistically significant with P< 0.05 [Figure 5]. The mean total use of phenylephrine was lower in group O when compared with group P and the difference between both the groups was statistically significant with P< 0.05 [Figure 6]. Neonatal parameters were also better with the use of ondansetron as observed by statistically significant difference in Apgar score at 1 min (P < 0.05).
Figure 1: Trends in mean heart rate

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Figure 2: Trends in mean systolic blood pressure

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Figure 3: Trends in mean diastolic blood pressure

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Figure 4: Trends in mean arterial pressure

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Figure 5: Total intraoperative fluid administered (mL)

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Figure 6: Total use of phenylephrine (μg)

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  Discussion Top


SAB for caesarean sections is associated with significant bradycardia and hypotension which may compromise the health of the mother and the fetus. It produces vasodilation, hypotension, and bradycardia by sympathetic blockade and BJR via stimulation of 5-HT3 receptors in vagal nerve endings.[10] However, in some cases tachycardia may occur: (1)as a compensatory response to a rapid reduction in systemic vascular resistance,[12] (2) due to severe local anesthetic systemic toxicity,[13] and (3) associated with ST segment changes.[14] In this study, it was postulated that ondansetron nt SABcan preve-induced bradycardia and hypotension by preventing serotonin-induced BJR. Ondansetron is a highly selective 5-HT3 receptor antagonist, has onset of action in less than 30 min (i.v. administration), peak effect in 10 min, half-life of approximately 4 h, and exact duration unknown. The dose of ondansetron used in our study was4 mg. It was found to be the optimal dosage for prevention of maternal hypotension during caesarean sections in a previous study conducted by Wang et al.[8] and also because of increased risk of QT prolongation with higher dose.We observed that in group O, where parturients received 4 mg ondansetron 10 min before initiation of SAB, the fall in SBP, DBP, and MAP was significantly less when compared with the placebo group. This attenuation was observed from the time of initiation of SAB upto 12 min of surgery time.

Our findings are consistent with the results of Trabelsi et al. with respect to attenuation of SBP, DBP, and MAP. However, we did not observe any effect of ondansetron on HR at any time during the study period, contrary to their findings.[15] This difference may be attributed to an infrequent incidence of bradycardia in both the groups. With respect to HR, our results were consistent with the findings of Owczuk R, et al., Sahoo, et al., and Wang et al. On the other hand, studies by Marashi et al. and Trabelsi et al. found ondansetron to be successfully able to attenuate SAB-induced bradycardia when compared with placebo.[9],[10],[15],[16],[17]

Sahoo et al. and Wang et al. observed attenuation of fall in SBP and MAP with the use of ondansetron in caesarean sections. However, none of these studies reported a statistically significant effect of ondansetron on DBP which was observed in our study. This can be ascribed to a small sample size in their studies (n = 52 and 66, respectively) which could not achieve statistical significance when compared with 150 parturients in our study.[10],[16]

Our results are contrary to the findings of Ortiz-Gomez et al., Marciniak et al., and Terkawi et al. who found ondansetron to be ineffective in attenuating both hypotension and bradycardia after administration of SAB.[6],[18],[19] This could be due to difference in the dose of bupivacaine used or due to addition to opioid adjuncts intrathecally in their studies.

With respect to the mean total use of vasopressor (phenylephrine), our results are consistent with the findings of Marashi et al., Sahoo et al., and Wang et al. in terms of decreased vasopressor requirement with the use of ondansetron when compared with a placebo.[10],[16],[17] A statistical significance difference in the total amount of fluid administered was observed (P < 0.05) which may be attributed to higher amounts of vasopressor and fluid requirements of the placebo group to maintain SBP within 80% of the baseline value. None of the previous studies has commented upon the effect of ondansetron on the total intraoperative fluid requirement of the parturient. Only two patients in the placebo group required the use of atropine for the management of bradycardia after administration of SAB when compared with none in the ondansetron group and the difference was not statistically significant (P = 0.157). With respect to the neonatal parameters, the difference in mean Apgar score at 1 min between the two groups was statistically significant (P = 0.013).

The study period was specifically restricted between subarachnoid administration of local anesthetic and the delivery of baby to avoid confounding by the effects of uterotonic drugs, blood loss during the extraction of placenta, and vagal responses to uterine externalization.

The limitations of our study include inability to evaluate the effect of ondansetron on the total duration of sensory and motor blockade. In addition, we also cannot comment upon its effect on HR due to an infrequent occurrence of bradycardia in our study population. Our study was superior to the other studies in terms of a large sample size including 150 parturients. Also, ondansetron was administered 10 min before the initiation of SAB to achieve its peak action when compared with 5 minutes in previous studies.


  Conclusion Top


We conclude that i.v. ondansetron premedication can successfully attenuate SAB-induced fall in SBP, DBP, and MAP in parturients scheduled for elective caesarean sections.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Yeoh, Brian S, Leong SB, Heng AST. Anaesthesia for lower-segment caesarean section: Changing perspectives. Indian J Anaesth 2010;54.5:409-14.  Back to cited text no. 1
    
2.
Terkawi AS, Mavridis D, Flood P, Wetterslev J, Terkawi RS, Bin Abdulhak AA, et al. Does ondansetron modify sympathectomy due to subarachnoid anesthesia? Anesthesiology 2016;124:1.  Back to cited text no. 2
    
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Rollins M, Lucero J. Overview of anesthetic considerations for Cesarean delivery. Br Med Bull 2012;101:105-25.  Back to cited text no. 3
    
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Terkawi AS, Tiouririne M, Mehta SH, Hackworth JM, Tsang S, Durieux ME, et al. Ondansetron does not attenuate hemodynamic changes in patients undergoing elective cesarean delivery using subarachnoid anesthesia: A double-blind, placebo controlled, randomized trial. Reg Anesth Pain Med 2015;40:344-8.  Back to cited text no. 6
    
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Nallam SR, Dara S. Effect of intravenous ondansetron on reducing the incidence of hypotension and bradycardia events during shoulder arthroscopy in sitting position under interscalene brachial plexus block: A prospective randomized trial. Indian J Anaesth 2015;59:353-8.  Back to cited text no. 7
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Owczuk R, Wenski W, Polak-Krzeminska A, Twardowski P, Arszułowicz R, Dylczyk-Sommer A, et al. Ondansetron given intravenously attenuates arterial blood pressure drop due to spinal anesthesia: A double-blind, placebo controlled study. Reg Anesth Pain Med 2008;33:332-9.  Back to cited text no. 9
    
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Sahoo T, Sen Dasgupta C, Goswami A, Hazra A. Reduction in spinal-induced hypotension with ondansetron in parturients undergoing caesarean section: A double-blind randomized, placebo-controlled study. Int J Obstet Anesth 2012;21:24-8.  Back to cited text no. 10
    
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