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ORIGINAL ARTICLE
Year : 2021  |  Volume : 11  |  Issue : 1  |  Page : 15-19

Intravenous ondansetron to prevent hypotension during cesarean section under spinal anaesthesia


1 Department of Anaesthesiology, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India
2 ESIC Medical College and Hospital, Faridabad, Haryana, India

Date of Submission05-Jul-2020
Date of Acceptance07-Jul-2020
Date of Web Publication16-Apr-2021

Correspondence Address:
Dr. Anil Kumar Bhiwal
B-2/S-4 Doctor Quarter, Geetanjali Medical College and Hospital, Udaipur – 313 001, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/joacc.JOACC_61_20

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  Abstract 


Background: Spinal anesthesia for cesarean section (CS) is associated with common side effects like hypotension and bradycardia. Ondansetron, a 5HT3 receptor antagonist, inhibits Bezold-Jarish reflex and has been found to be effective for prevention of spinal-induced hypotension for elective cesarean section. Aims: The aim of this study was to evaluate the effect of two different doses of ondansetron as prophylaxis to prevent hypotension during spinal anesthesia for caesarean section. Materials and Methods: This prospective randomized double-blinded controlled study was conducted on 150 full-term parturients undergoing CS under spinal anesthesia, who were divided into three groups, receiving saline or different drug doses: Group C: 0.9% Normal Saline 10 ml; Group O4: 4 mg Ondansetron in 8 ml NS; or Group O8: 8 mg Ondansetron in 6 ml NS, 5 min before spinal anesthesia. All the patients were monitored for blood pressure, heart rate, vasopressor requirement, and side effects. Hemodynamic variables and demographic data were compared by analysis of variance (ANOVA) and Chi-square test was used for analyzing adverse effects and P value <0.05 was considered significant. Results: Intraoperative incidence of hypotension was significantly high (P < 0.001) in group C (58%) as compared to group O8 (16%) and group O4 (31.25%) but comparable between ondansetron groups (O8 vs. O4) (P = 0.074). Total requirement of ephedrine (mg) was significantly higher (P < 0.01) in group C (5.02 ± 4.95) as compared to group O8 (1.2 ± 3.20) and O4 (3.00 ± 4.88). It was found to be significantly higher (P = 0.034) in group O4 when compared with group O8. Mean HR, SBP, DBP, MAP was decreased more in group C at different time intervals. Conclusions: Prophylactic intravenous ondansetron reduced the incidence of hypotension and requirement of vasopressors in parturients undergoing CS under spinal anesthesia, with a further decrease in requirement of vasopressor in Group O8.

Keywords: Bezold-Jarisch reflex, caesarean section, ondansetron, spinal induced hypotension


How to cite this article:
Bhiwal AK, Chauhan K, Choudhary S, Bhatt HA, Gupta S. Intravenous ondansetron to prevent hypotension during cesarean section under spinal anaesthesia. J Obstet Anaesth Crit Care 2021;11:15-9

How to cite this URL:
Bhiwal AK, Chauhan K, Choudhary S, Bhatt HA, Gupta S. Intravenous ondansetron to prevent hypotension during cesarean section under spinal anaesthesia. J Obstet Anaesth Crit Care [serial online] 2021 [cited 2021 Jun 15];11:15-9. Available from: https://www.joacc.com/text.asp?2021/11/1/15/313913




  Introduction Top


Maternal hypotension is the most frequent complication following spinal anesthesia (SA) with a reported incidence of 50–80%. This can lead to adverse effects in both the mother (nausea, vomiting, dizziness, decreased consciousness, bradycardia) and the fetus (decreased uteroplacental blood flow, impaired fetal oxygenation, fetal acidosis).[1]

Following SA, maternal hypotension and bradycardia, occurs due to sympathetic blockade with a parasympathetic overdrive which leads to decrease in systemic vascular resistance and cardiac output with decrease in venous return to the heart.[2] Bezold–Jarisch reflex (BJR) is mediated by stimulation of intracardiac receptors including mechanoreceptors and chemoreceptors. Mechanoreceptors located in all cardiac chambers are sensitive to decreased venous return resulting in stimulation, of receptors and activation of BJR. Chemoreceptors are sensitive to serotonin released from activated thrombocytes, and are an important factor for triggering BJR during hypovolemic conditions. This causes an increased efferent vagal signalling leading to bradycardia and further hypotension.[3],[4]

Ondansetron, a 5-Hydroxytryptamine (5HT3) receptor antagonist, inhibits BJR, and has been found to be effective for the prevention of spinal induced hypotension in elective cesarean section (CS) patients and non-obstetric patients.[5],[6]

The effect of different doses of ondansetron to reduce the incidence of maternal hypotension has been found to show varying results.[7],[8]

Thus, this prospective randomized double-blinded study was conducted to evaluate the effect of two different doses of intravenous ondansetron as prophylaxis to reduce the incidence of hypotension during SA in parturients scheduled for elective CS.


  Materials and Methods Top


After obtaining approval from the institutional research ethics board (GU/HREC/EC/2017/42) and informed patient consent, this prospective randomized double-blinded controlled study was conducted on 150 full-term parturients, age 18–40 years, ASA I and II undergoing elective CS under spinal anesthesia. Parturients having history of allergy to ondansetron or local anesthetic, obesity, pregnancy induced hypertension, or any other associated comorbid conditions were excluded from the study.

All the parturients were randomly assigned to three groups using computer generated randomization chart, receiving Normal Saline 0.9%10 ml (Group C), or Ondansetron 4 mg diluted in 8 ml NS (Group O4), or 8 mg diluted in 6 ml NS (Group O8) 5 min before spinal anesthesia.

Procedure and conduct of study

The selected patients underwent a pre-anaesthetic check-up a day prior to surgery and were advised for overnight fasting. Peripheral 18-gauge IV cannula was inserted and inj. ranitidine (1 mg/kg) IV, inj. metoclopramide (0.2 mg/kg) IV for acid prophylaxis was administered in the pre-anaesthesia room. Ringer lactate 10 mL/kg was infused over 30 min before SA. In the operating room baseline values of haemodynamic variables (HR, SBP, DBP, and MAP) were recorded. The study drug was given 5 min before the sub-arachnoid block. Spinal anesthesia was performed with a 25-G Quincke spinal needle in the left lateral position at L3-4 or L4-5 in a dose of 2 ml 0.5% hyperbaric bupivacaine.

Sensory block was assessed using pin prick technique in mid clavicular line bilaterally at 1 min interval while motor block was assessed using Modified Bromage score and surgery was allowed when the block height was achieved at T-6 level. Hemodynamic parameters like heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and oxygen saturation (SpO2) were recorded at the time of spinal block (0 min) and at 2-min interval up to 20 min, followed by 5-min interval upto 30 min or till the end of surgery.

Hypotension was defined as a fall in SBP >20% of baseline and was treated with inj. ephedrine 6 mg intravenously. Bradycardia was defined as HR <50 beats/min and was treated with inj. atropine 0.6 mg intravenously. The incidence of hypotension, bradycardia, and requirement of ephedrine and atropine were recorded. Patients were also assessed for the presence of nausea, vomiting, rigor, discomfort, or shivering. Rigors and pain was treated with inj. tramadol 25 mg IV and inj. fentanyl 50 μg intravenously, respectively. Nausea and vomiting was treated with inj. promethazine 12.5 mg intravenously. Demographic characteristics like age, weight, height, gestation week, time from spinal anesthesia to delivery, duration of surgery and APGAR score of the baby at 1 min and 5 min were recorded.

The primary outcome of this study was the incidence of maternal hypotension in all three groups while secondary outcomes included the total dose of ephedrine and atropine requirement, adverse effects and APGAR score of baby.

Statistical analysis

Sample size was calculated using software EpiInfo™ 7 with the assumption of alpha error 5%, that is, confidence level 95%, and beta error to be 20%, that is, power of study to be 80% and odds ratio of 2, a sample size of 50 patients in each group was considered to be sufficient to detect a 20% reduction in SBP among the groups. Thus, total of 150 patients were considered for the study.

Data were presented as mean, standard deviation, median (range), or percentage, as appropriate. Statistical analysis was performed using SPSS package (version 17, SPSS, Chicago, IL). Hemodynamic variables and demographic data were compared by analysis of variance (ANOVA) test while Chi-square test was used for adverse effects and P < 0.05 was considered significant.


  Results Top


One hundred and fifty parturients were enrolled in the study but two patients in Group O4 were excluded due to inadequate anesthesia after spinal block.

The demographic data in the three groups regarding mean value of age, height, weight, and gestation week were comparable. Duration of surgery, time from spinal anesthesia to delivery and APGAR score at 1 min and 5 min were also comparable between the three groups [Table 1].
Table 1: Comparison of demographics, obstetric data and neonatal outcome

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No statistical significance was observed in the sensory and motor block characteristics. The baseline HR, SBP, DBP, MAP were comparable in all groups (P > 0.05) [Figure 1].
Figure 1: Comparison of Hemodynamic variables between the groups at different time intervals

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Intraoperative incidence of hypotension was significantly higher (P < 0.001) in group C (58%) as compared to group O8 (16%) and group O4 (31.25%). Total requirement of ephedrine (mg) was also significantly higher (P < 0.01) in group C (5.02 ± 4.95) when compared to group O8 (1.2 ± 3.20) and O4 (3.00 ± 4.88) [Table 2].
Table 2: Comparison of incidence of hypotension and requirement of ephedrine in different groups

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On comparison of group O8 and O4, the incidence of hypotension was higher in O4 group (31.25%) as compared to O8 (16%) (P = 0.074) while the requirement of total dose of ephedrine was found to be significantly higher (P = 0.034) in O4 as compared to O8.

The mean HR was decreased more in group C which was found to be statistically significant at all-time intervals (P < 0.05) except at 10 and 25 min. On intergroup comparison (O8 vs O4) the HR was significantly higher in O8 at 20 and 25 min (P < 0.05). Bradycardia was found only in one patient of group O4 and control group [Figure1].

SBP decreased from base line in all three groups which was significantly more in control group at different time intervals (0, 2, 6, 8, 12, 14, 16, and 20 min; P < 0.05). On comparing group O4 and O8 SBP was significantly different at 8, 18, and 20 min following spinal anaesthesia (P < 0.05) [Figure 1].

The decrease in MAP was more in control group at 16 and 30 min (P < 0.05) while the difference in MAP between group O8 and group O4 was found to be significant only at 16 min (P < 0.05) [Figure 1].

The incidence of vomiting was high in control group but difference was statistically non-significant (P = 0.06) while shivering was found only in 7 patients of control group [Table 3].
Table 3: Comparison of incidence of side effects

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  Discussion Top


Hypotension is the most common side effect encountered after administration of SA in CS. The major causes attributed to spinal induced hypotension are sympathetic blockade with a parasympathetic overdrive, aortacaval compression caused by gravid uterus and BJR. Ondansetron, a 5HT3 receptor antagonist, attenuates arterial hypotension and bradycardia by blunting the BJR and reducing the need of vasopressors and its consequent effects on uterine blood flow during CS under spinal anesthesia.[9] Thus it has a favorable influence on fetal umbilical acid–base profile with a higher venous pH. The effect of different doses of ondansetron on prevention of spinal induced hypotension has been found to vary in different studies.[7],[8] Thus, this study was designed to assess the effect of ondansetron on prevention of spinal induced hypotension, in two different doses (4 mg and 8 mg).

The incidence of hypotension and requirement of ephedrine was significantly greater in the control group as compared to ondansetron groups (O4 and O8). Group O8 showed a significantly decreased (P = 0.034) requirement of Ephedrine as compared to group O4. The incidence of hypotension was also reduced in group O8 as compared to O4 but it did not reach statistical significance (P = 0.074). Wang et al.[8] reported a dose–response relationship between ondansetron (2, 4, 6, and 8 mg) and prevention of maternal hypotension and found that ondansetron 4 mg and 6 mg reduced the incidence of maternal hypotension and vasopressor requirement as compared with ondansetron 2 mg and 8 mg while in our study ondansetron 8 mg was found more effective in decreasing the requirement of ephedrine.

Similarly, Potdar et al.[7] also found significantly higher incidence of hypotension and requirement of ephedrine in control group as compared to ondansetron groups but they did not find any additional advantage of 8 mg of ondansetron over 4 mg which may be due to no hemodynamic monitoring after ephedrine administration. Other authors[10],[11] have also found less incidence of hypotension and requirement of vasopressor in ondansetron group as compared to control group. Karacaer et al.[12] found no significant difference in the incidence of hypotension but the cumulative episodes of hypotension and norepinephrine consumption were significantly greater in control group than in ondansetron (8 mg) group. Ortiz-Gomez et al.[13] found the incidence of hypotension in control group and ondansetron group (2, 4, and 8 mg) were comparable but larger doses of ondansetron significantly decreased ephedrine requirement in a dose-dependent fashion. Some authors[14],[15] did not find any difference in the incidence of hypotension and requirement of vasopressors in the placebo and ondansetron groups. This could be due to difference in study population, sample size, study design, definition of hypotension, dose and timing of ondansetron administration, anaesthetic technique, larger doses of bupivacaine and addition of opioid adjuncts.

The decrease in HR after SA was more in control group at all-time intervals (P < 0.05) except at 10 and 25 min. Bradycardia (HR < 50 bpm) was found only in one patient in group O4 and control group. Sahoo T et al.[10] found a decrease in HR which was more common in the saline Group, but differences were statistically significant only at 24 and 45 min as compared to O4 group and bradycardia was found only in 2 patients in the control group. Similarly, other authors[7],[11],[13],[14] found a change in HR at different time intervals among the Ondansetron groups and control group which was comparable.

The decrease in SBP, DBP, MAP from baseline was found in all three groups, however in group C the decrease was more evident while in group O8 these variables were maintained closer to the baseline at all-time intervals. Similar to our study, other authors[7],[10],[11] have also found the changes in hemodynamic parameters, more in control group as compared to the study groups. Our results are contrary to the findings of other authors[13],[14],[15],[16] who found no significant differences in the hemodynamic variables.

In our study, the incidence of vomiting was higher in control group which was similar to Sahoo et al.[10] while Ortiz-Gomez et al.[13] did not find any significant difference between the groups. Several studies have demonstrated that ondansetron can significantly reduce the incidence of postoperative nausea and vomiting[7],[10],[13] as also seen in our study though it did not reach statistical significance. The 5-HT3 receptor- induced vagal stimulation and 5-HT release in the fourth ventricle caused by vagal excitement are both blocked and inhibited by ondansetron leading to effective control of vomiting.

Shivering was found only in 7 patients in the control group which was similar to Badway et al.[11] who also found a higher incidence of shivering in the control group as compared to ondansetron group. Ondansetron has been proved to possess anti-shivering properties, but the mechanism, though not clear, has been attributed to its central action in inhibiting serotonin reuptake at the level of the pre-optic anterior hypothalamic region.[17],[18]

Further research, should be directed toward finding an optimum dose of ondansetron (mg/kg), timing of ondansetron administration, and the effect of combination of both ondansetron and vassopressors as prophylaxis to prevent post spinal hypotension.


  Conclusion Top


In conclusion, intravenous ondansetron given 5 min before spinal anaesthesia can decrease the incidence of hypotension and requirement of vasopressors in parturients undergoing CS under spinal anesthesia, while 8 mg can further reduce the requirement of vasopressor.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Stewart A, Fernando R, McDonald S, Hignett R, Jones T, Columb M. The dose-dependent effects of phenylephrine for elective cesarean delivery under spinal anesthesia. Anesth Analg 2010;111:1230-7.  Back to cited text no. 1
    
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Loubert C. Fluid and vasopressor management for Cesarean delivery under spinal anesthesia: Continuing professional development. Can J Anaesth 2012;59:604–9.  Back to cited text no. 2
    
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Veelken R, Hilgers KF, Leonard M, Scrogin K, Ruhe J, Mann JF, et al. A highly selective cardiorenal serotonergic 5-HT3 mediated reflex in rats. Am J Physiol 1993;264:H1871-7.  Back to cited text no. 3
    
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Yamano M, Kamato T, Nishida A, Ito H, Yuki H, Tsutsumi R, et al. Serotonin (5-HT) 3- receptor antagonism of 4,5,6,7-tetrahydrobenzimidazole derivatives against 5-HT-induced bradycardia in anesthetized rats. Jpn J Pharmacol 1994;65:241-8.  Back to cited text no. 4
    
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Wang Q, Zhuo L, Shen MK, Yu YY, Yu JJ, Wang M. Ondansetron preloading with crystalloid infusion reduces maternal hypotension during Cesarean delivery. Am J Perinatol 2014;10:913-22.  Back to cited text no. 5
    
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Christofaki M, Papaioannou A. Ondansetron: A review of pharmacokinetics and clinical experience in postoperative nausea and vomiting. Expert Opin Drug Metab Toxicol 2014;10:437-44.  Back to cited text no. 6
    
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Potdar MP, Kamat LL, Jha TR, Talnikar AS, Mahevi ZM, Save MP. Effects of ondansetron in attenuation of post spinal hypotension in caesarean section: A comparison of two different doses with placebo. J Obstet Anaesth Crit Care 2017;7:69-74.  Back to cited text no. 7
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Wang M, Zhuo L, Wang Q, Shen MK, Yu YY, Yu JJ, et al. Efficacy of prophylactic intravenous ondansetron on the prevention of hypotension during caesarean delivery: A dose-dependent study. Int J Clin Exp Med 2014;7:5210–6.  Back to cited text no. 8
    
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Sahoo T, SenDasgupta C, Goswami A, Hazra A. Reduction in spinal-induced hypotension with ondansetron in parturients undergoing caesarean section: A double-blind randomised, placebo controlled study. Int J Obstet Anesth 2012;21:24–8.  Back to cited text no. 10
    
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Badway AA, Moktar AM. The role of ondansetron in prevention of post spinal shivering (PSS) in obstetric patients: A double-blind randomized controlled trial. Egypt J Anaesth 2017;33:29-33.  Back to cited text no. 11
    
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Karacaer F, Biricik E. Does prophylactic ondansetron reduce norepinephrine consumption in patients undergoing caesarean section with spinal anesthesia. J Anesth 2018;32:90-7.  Back to cited text no. 12
    
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Ortiz-G´omez JR, Palacio-Abizanda FJ, Morillas-Ramirez F, Fornet- Ruiz I, Lorenzo-Jim´enez I, Bermejo-Albares ML. The effect of intravenous ondansetron on maternal haemodynamics during elective caesarean delivery under spinal anaesthesia: A double-blind, randomised, placebo-controlled trial. Int J Obstet Anesth 2014;23:138–43.  Back to cited text no. 13
    
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Terkawi AS, Tiouririne M, Mehta HS, Hackworth JM, Tsang S, Durieux ME. Ondansetron does not attenuate hemodynamic changes in patients undergoing elective caesarean delivery using subarachnoid anesthesia: A double-blind, placebo-controlled, randomized trial. Reg Anesth Pain Med 2015;40:344-8.  Back to cited text no. 14
    
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