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Year : 2020  |  Volume : 64  |  Issue : 11  |  Page : 954-959  

The effect of ondansetron administration 20 minutes prior to spinal anaesthesia on haemodynamic status in patients undergoing elective caesarean section: A comparison between two different doses

Department of Anaesthesia, School of Medicine, The University of Jordan, Amman, Jordan

Date of Submission19-Jan-2020
Date of Decision27-Apr-2020
Date of Acceptance21-May-2020
Date of Web Publication1-Nov-2020

Correspondence Address:
Prof. Subhi M Alghanem
Department of Anesthesia, School of Medicine, University of Jordan. PO Box 13046, Amman - 11942
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ija.IJA_974_19

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Background and Aims: Spinal anaesthesia is currently the most common method used for managing patients undergoing elective caesarean sections. Recent meta-analyses have been supporting the use of 5-HT3 antagonists, like ondansetron, to attenuate hypotension induced by spinal block. Various doses of ondansetron were given intravenously five minutes before spinal block. However, a consensus on definitive dose and timing for maximal benefit is yet to be agreed upon. Methods: Our prospective randomised clinical trial investigated a new approach by administrating intravenous ondansetron 20 minutes before spinal anaesthesia. This work investigated ondansetron effect on both haemodynamic changes and vasopressors use by dividing patients into three groups. The first group O4 (n = 51) received 4 mg ondansetron, the second group O6 (n = 51) received 6 mg ondansetron, and the control group C (n = 50) received normal saline. We recorded systolic blood pressure (SBP), diastolic blood pressure (DBP) and the mean blood pressure (MBP) at different time intervals. Results: There was no significant difference in blood pressure measurements among the study groups (P > 0.05). The consumption of ephedrine in the control group is higher than both of the ondansetron groups (P > 0.001), with a mean dose of 27.2 ± 20.5 mg of ephedrine for group C, compared to 17.8 ± 14.9 and 14.7 ± 11.3 in O4 and O6 groups, respectively. Episodes of hypotension and number of patients with hypotension were not significantly different among the studied groups (P = 0.07; P = 0.96, respectively). Conclusions: Prophylactic 4 and 6 mg ondansetron given 20 minutes before spinal anaesthesia in caesarean section does not reduce the incidence of hypotension.

Keywords: Caesarean section, hypotension, intraoperative complications, ondansetron

How to cite this article:
Samarah WK, Alghanem SM, Bsisu IK, Rahman ZA, Guzu HA, Abufares BN. The effect of ondansetron administration 20 minutes prior to spinal anaesthesia on haemodynamic status in patients undergoing elective caesarean section: A comparison between two different doses. Indian J Anaesth 2020;64:954-9

How to cite this URL:
Samarah WK, Alghanem SM, Bsisu IK, Rahman ZA, Guzu HA, Abufares BN. The effect of ondansetron administration 20 minutes prior to spinal anaesthesia on haemodynamic status in patients undergoing elective caesarean section: A comparison between two different doses. Indian J Anaesth [serial online] 2020 [cited 2021 Jun 23];64:954-9. Available from: https://www.ijaweb.org/text.asp?2020/64/11/954/299696

   Introduction Top

Spinal anaesthesia has become the routine standard of care in managing patients undergoing elective caesarean sections,[1] as there is an increased risk of aspiration pneumonitis, difficult airways and foetal exposure to hypnotic drugs in patients undergoing general anaesthesia. Spinal anaesthesia is a safe and effective choice, but it has its own array of unwanted side effects that may affect the mother and the unborn child's well-being, most commonly hypotension and bradycardia. Spinal anaesthesia induced hypotension is of special concern as it happens in around one-third of non-obstetric patients, compared to 70-80% in obstetric population in which the first 10 minutes are critical in terms of haemodynamic response to spinal anaesthesia.[2],[3],[4],[5] Maternal hypotension results mainly from the direct sympathectomy at the level of the block causing decrease in cardiac output and systemic vascular resistance due to sympatholysis secondary to local anaesthetic effects on spinal sympathetic outflow. Bradycardia is thought to be attributed to the Bezold-Jarisch reflex, this reflex is an inhibitory parasympathetic reflex originating in cardiac sensory receptors caused by decreased filling of the right atrium which stimulate the peripheral serotonin 5-hydroxytryptamine- receptors (5-HT3 type) mediated by serotonin.[6],[7]

Current research in animals, obstetric, and non-obstetric populations indicates that 5-HT3 antagonists may abolish the Bezold-Jarisch reflex. Ondansetron is 5-HT receptors antagonist, which is basically used as an antiemetic drug and is thought to counteract bradycardia and hypotension induced by spinal block. In the literature, ondansetron was used 5 minutes before performing spinal block to prevent hypotension and bradycardia with moderate reduction in hypotension during caesarean section.[6] Ondansetron has its peak plasma concentration within 30 minutes of intravenous administration when used to treat nausea and vomiting.[8],[9],[10] In our presenting clinical trial, we propose that giving ondansetron 20 minutes before performing spinal block should improve the efficacy of counteracting hypotension of spinal block in caesarean section. Our primary aim was to assess systolic blood pressure (SBP), diastolic blood pressure (DBP), and the mean blood pressure (MBP) among different ondansetron doses and a control group in different time intervals.

   Methods Top

This was a prospective, double-blinded, placebo-controlled, randomised clinical trial. After approval from the University of Jordan Hospital institutional review board (2433 / 2016/10) on February 21st, 2016, and the clinical trial number (NCT04140058), as retrospectively registered on clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT04140058), a written informed consent was obtained from all participants. The study was conducted in concordance with the latest declaration of Helsinki. The study took place in the period from January 2017 to January 2018. To estimate the sample size, we used the G-power software where we used the following input to calculate apriori mean difference between the groups: a reduction of 50% in the incidence of hypotension,[11] alpha error of 0.05, a power of 0.8, yielding a total of 43 participants for each of the three groups. We further increased the sample size of the groups to 50 patients per group to increase the power of the study.

Patients were randomly allocated using www.randomiser.org into three groups: The first group O4 (n = 51) received 4 mg ondansetron, the second group O6 (n = 51) received 6 mg ondansetron, and the control group C (n = 50) received normal saline. All injections were diluted in 10 ml of normal saline and given intravenously 15-20 minutes before the intrathecal injection. A research assistant prepared the injection for a consultant anaesthetist who was blinded about the injection administered.

This study included patients who received spinal anaesthesia for elective caeserean sections who met the American Society of Anesthesiologists (ASA) physical status classification II. Exclusion criteria consisted of patients ASA physical status classification III, IV or V, emergent caeserean sections, multiple parities (twins/triplets), expected blood loss more than 1,000 ml, more than 6 mg ondansetron administered, patients who presented with a cardiac history (coronary artery disease, myocardial infarction, congestive heart failure, murmur, mitral valve prolapse/regurgitation, dysrhythmias, aortic stenosis/regurgitation), patients who presented with preeclampsia, and patients who presented for caeserean section with epidural catheter due to failure to progress.

Preoperative assessment was done by an anaesthetist the day before surgery, informed written consent was obtained from all participants. All patients were fasted for 8 hours and were not given premedication other than omeprazole 40 mg orally 6 hours pre-operatively and ranitidine 50 mg intravenously 2 hours pre-operatively. Demographic data such as age, weight, height, body mass index were recorded. In the operating theatre, baseline values of non-invasive systolic blood pressure (SBP) and diastolic blood pressure (DBP), and mean arterial pressure (MAP) were obtained. In addition, heart rate (HR) and pulse oximetry (SpO2) were recorded, and two intravenous gauge 18 cannulae were secured in each patient. All patients were preloaded with 500 ml of lactated Ringer's solution. Then, patients were put in a sitting position and under aseptic technique, a subarachnoid block was done by injecting 2 mL of 0.5% (10 mg) hyperbaric bupivacaine and 25 μg fentanyl through a 25 gauge Whitacre pencil point spinal needle at the level of L3-L4 or L4-L5. Each patient was then immediately put in the supine position with left uterine displacement. Sensory block levels were assessed every minute after subarachnoid block using perception to cold, and motor block levels using modified Bromage scale.[12] SBP, DBP, and HR were measured and MBP was calculated using aforementioned formula, at 1-minute intervals for ten minutes, 2-minute intervals for another 10 minutes, then at 5-minute intervals till 40 minutes after spinal block by a blinded anaesthesiologist. Hypotension was defined as drop in SBP ≥20% of the baseline value or SBP less than 100 mmHg. The hypotension was treated by increasing rate of crystalloids infusion and intravenous (IV) ephedrine doses as follows: IV ephedrine 6 mg if SBP is <100 mmHg, IV ephedrine 9 mg if SBP is <90 mmHg, IV ephedrine 12 mg if SBP is <80 mmHg, IV ephedrine 15 mg if SBP is <70 mmHg.

Bradycardia was defined as ≥30% drop from baseline heart rate or when the HR dropped below 50 beats per minute; the patient was treated with IV atropine 0.5 mg. During anaesthesia, Ringer's lactated or normal saline solutions were administered to cover maintenance and deficits besides treating hypotension, also blood loss was monitored for possible blood transfusion. After delivery of the foetus, all patients received 10 international units of oxytocin direct IV and then 30 international units in 250 ml compatible IV fluids over four hours. Intraoperative nausea and vomiting were treated with elevation of blood pressure and any patient who received intraoperative antiemetic therapy was excluded from the study.

Statistical Package for Social sciences (SPSS) version 21.0 (Chicago, USA) was used in our analysis. Demographic data which include age, weight, height, SBP, DBP, MBP, HR and SpO2 were analysed using One-way analysis of variance (ANOVA). After spinal block SBP, DBP, MBP, HR, IV fluid infusion, blood loss and ephedrine doses were analysed using one-way ANOVA and when there was a statistically significant difference (P value less than 0.05), we used to do the least significance difference (LSD) posthoc analysis in different time intervals. Chi-square test was used to compare between the three groups regarding episodes of hypotension requiring treatment with ephedrine, the number of patients requiring dose of ephedrine equal to or more than 15 mg, and the overall number of hypotensive episodes. All underlying assumptions were met, unless otherwise indicated. P value less than 0.05 was considered statistically significant.

   Results Top

152 pregnant patients were prospectively enroled during the study period. There were 50 patients in the control group (group C) and 51 patients in ondansetron 4 mg (group O4) and ondansetron 6 mg (group O6). The study groups were shown to be statistically comparable with regard to demographic variables and baseline parameters, as shown in [Table 1]. There was no statistically significant difference in the readings of SBP, DBP, and MBP among the three groups in different time intervals after spinal block as shown in [Table 2]. As for heart rate readings significant difference was exhibited between the three groups (P <.05). Details for HR differences are shown in [Table 3].
Table 1: Demographic and anaesthetic data

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Table 2: Mean rates of Systolic blood pressure (SBP), Diastolic blood pressure (DBP), Mean Arterial Pressure (MAP), based on certain measurement time points in the study groups

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Table 3: Comparison between the three groups in Heart Rate (HR)

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ANOVA test showed a significant difference on the usage of ephedrine among the three groups (P <.001). The Posthoc comparison showed that patients in group C received significantly higher dose of ephedrine per patient compared with patients in the other two groups; significance (P =.004) for group O4 and (P <.001) for group O6. The standard errors (S.E.) of the dose of ephedrine were 2.9 for group C, 2.1 for group O4, and 1.6 for group O6 [Table 4]. Furthermore, the number of times ephedrine was given in response to drop in blood pressure over different phases of the study after spinal block was higher among patients in group C as shown in [Table 4]. Significantly more patients in group C received high doses of ephedrine (15 mg-30 mg) to treat intraoperative hypotension in different time intervals compared with group O4 and group O6. Neither number of patients with hypotension, nor total number of hypotensive episodes were significantly different between the study groups, as demonstrated in [Table 5].
Table 4: Comparison of the mean of ephedrine doses among the 3 study groups

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Table 5: Patients with different doses of ephedrine, with hypotension and overall hypotensive episodes

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   Discussion Top

Spinal anaesthesia has become the standard anaesthetic technique for caesarean section since it helps to avoid the risks accompanying general anaesthesia. But spinal anaesthesia has its own complications notably post spinal hypotension with or without bradycardia.[13] Hypotension after spinal block during caesarean section is common and the main treatment and prevention relies on IV fluids infusion and vasopressors administration such as phenylephrine, ephedrine, mephentermine.[14] Several studies have shown that ondansetron, which is basically an antiemetic drug, is beneficial in reducing incidence of hypotension which accompanies spinal block in caesarean section. Nearly in all these studies, ondansetron was given 5 minutes before initiation of spinal block.[15],[16],[17] Our study and work done by several previous researchers,[10] found that ondansetron reaches its peak plasma concentration within 30 minutes of IV administration. So, we injected ondansetron 20 minutes before spinal block and in 4 mg and 6 mg doses to see its effect in counteracting hypotension. We found that ondansetron in doses 4 and 6 mgs given 20 minutes before spinal block, and compared with saline did not reduce the incidence of hypotension in caesarean section. However, we found a dose dependant decrease in ephedrine requirement with the dose of ondansetron. In the current investigation, there was a high incidence of hypotension, the amount of IV crystalloids and the dose of ephedrine given were relatively high compared with other studies; possible explanation for this hypotension is that the protocol of oxytocin dose given to our patients is relatively high. Our findings coincide with the results shown by Ortiz- Gommez JR, et al.[18] with differences in the design of the study. For instance, the number of patients in their study was 32 patients in each group, the dose of bupivacaine was not fixed, and the dose of oxytocin was not mentioned. In another study,[17] 4 mg ondansetron given 5 minutes before spinal block for caesarean section attenuated mean blood pressure and diastolic blood pressure hypotension. Possible explanation to the discrepancy between their results and ours is that they did not use fentanyl in spinal block, the number of patients in each group of their study was 24 and the dose of oxytocin is not mentioned. Other investigators reported about ondansetron in obstetric patients undergoing caesarean section under spinal block that SBP, DBP, and the MBP was higher in patients who were given 5 mg ondansetron compared with the control. However, they used sufentanil as supplement for spinal block and oxytocin protocol administration was not known.[15] Another factor that may attribute to the incidence of post-spinal hypotension is the dose and the method of oxytocin administration.[11] One study concluded that 4 mg is the optimum dose of ondansetron for the prevention of hypotension after spinal block in caesarean section, however, they did not use fentanyl in spinal block, the protocol of oxytocin administration was giving 10 IU of oxytocin in 250 mL of normal saline as intravenous infusion, and they compared the changes in blood pressure, but not comparing the true values of blood pressures and heart rates.[11] Furthermore, ondansetron reduced hypotension in obstetric patients undergoing caesarean section but the preventive effect was not superior to vasoconstrictors.[19] In studies done on general surgical patients,[20] ondansetron administered 5 minutes before spinal block attenuated hypotension of the spinal block more than the control, but these clinical studies were in non-obstetric patients. Furthermore, a systematic review and meta-analysis done on this topic found that ondansetron reduces hypotension of spinal block in obstetric and non-obstetric patients,[21] while another systemic review and meta-analysis found that ondansetron is not effective in non-obstetric patients, while it was found effective in certain groups of obstetric patients.[6]

   Conclusion Top

In conclusion, our study indicated that despite giving ondansetron in doses of 4 mg and 6 mg 20 minutes before spinal block in the hope of increasing its efficacy, there was no reduction in the incidence of hypotension in caesarean section under spinal block, but there was a significant decrease in ephedrine consumption when compared to the placebo group.

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.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Lee A, Ngan Kee WD, Gin T. A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery. Anesth Analg 2002;94:920-6.  Back to cited text no. 1
Liu SS, McDonald SB. Current issues in spinal anesthesia. Anesthesiology 2001;94:888-906.  Back to cited text no. 2
Carpenter RL, Caplan RA, Brown DL, Stephenson C, Wu R. Incidence and risk factors for side effects of spinal anesthesia. Anesthesiology 1992;76:906-16.  Back to cited text no. 3
Mercier FJ, Auge M, Hoffmann C, Fischer C, Le Gouez A. Maternal hypotension during spinal anesthesia for caesarean delivery. Minerva Anestesiol 2013;79:62-73.  Back to cited text no. 4
Vos JJ, Scheeren TWL. Intraoperative hypotension and its prediction. Indian J anaesth 2019;63:877-85.  Back to cited text no. 5
[PUBMED]  [Full text]  
Heesen M, Klimek M, Hoeks SE, Rossaint R. Prevention of spinal anesthesia-induced hypotension during cesarean delivery by 5-hydroxytryptamine-3 receptor antagonists: A systematic review and meta-analysis and meta-regression. Anesth analg 2016;123:977-88.  Back to cited text no. 6
Mark AL. The Bezold-Jarisch reflex revisited: Clinical implications of inhibitory reflexes originating in the heart. J Am Coll Cardiol 1983;1:90-102.  Back to cited text no. 7
Bestas A, Onal SA, Bayar MK, Yildirim A, Aygen E. Effects of ondansetron and granisetron on postoperative nausea and vomiting in adult patients undergoing laparoscopic cholecystectomy: A randomized, double-blind, placebo-controlled clinical trial. Curr Ther Res Clin Exp 2007;68:303-12.  Back to cited text no. 8
Bhattacharya D, Banerjee A. Comparison of ondansetron and granisetron for prevention of nausea and vomiting following day care gynaecological laparoscopy. Indian J Anaesth 2003;47:249-82.  Back to cited text no. 9
Savant K, Khandeparker RV, Berwal V, Khandeparker PV, Jain H. Comparison of ondansetron and granisetron for antiemetic prophylaxis in maxillofacial surgery patients receiving general anesthesia: A prospective, randomised, and double blind study. J Korean Assoc Oral Maxillofac Surg 2016;42:84-9.  Back to cited text no. 10
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 cesarean delivery: A dose-dependent study. Int J Clin Exp Med 2014;7:5210.  Back to cited text no. 11
Rashad MM, Farmawy MS. Effects of intravenous ondansetron and granisetron on hemodynamic changes and motor and sensory blockade induced by spinal anesthesia in parturients undergoing cesarean section. Egypt J Anaesth 2013;29:369-74.  Back to cited text no. 12
Puthenveettil N, Sivachalam SN, Rajan S, Paul J, Kumar L. Comparison of norepinephrine and phenylephrine boluses for the treatment of hypotension during spinal anaesthesia for caesarean section - A randomised controlled trial. Indian J Anaesth 2019;63:995-1000.  Back to cited text no. 13
[PUBMED]  [Full text]  
Kinsella S, Carvalho B, Dyer R, Fernando R, McDonnell N, Mercier F, et al. International consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia. Anaesthesia 2018;73:71-92.  Back to cited text no. 14
Trabelsi W, Romdhani C, Elaskri H, Sammoud W, Bensalah M, Labbene I, et al. Effect of ondansetron on the occurrence of hypotension and on neonatal parameters during spinal anesthesia for elective caesarean section: A prospective, randomized, controlled, double-blind study. Anesthesiol Res Pract 2015;2015:158061.  Back to cited text no. 15
Marashi SM, Soltani-Omid S, Mohammadi SS, Aghajani Y, Movafegh A. Comparing two different doses of intravenous ondansetron with placebo on attenuation of spinal-induced hypotension and shivering. Anesth Pain Med 2014;4:e12055.  Back to cited text no. 16
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. 17
Ortiz-Gomez JR, Palacio-Abizanda FJ, Morillas-Ramirez F, Fornet-Ruiz I, Lorenzo-Jimenez A, 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. 18
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;31:913-22.  Back to cited text no. 19
Owczuk R, Wenski W, Polak-Krzeminska A, Twardowski P, Arszulowicz 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. 20
Tubog TD, Kane TD, Pugh MA. Effects of ondansetron on attenuating spinal anesthesia–induced hypotension and bradycardia in obstetric and nonobstetric subjects: A systematic review and meta-analysis. AANA J 2017;85:113-22.  Back to cited text no. 21


  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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