Subarachnoid block is a mainstay of anaesthesia in a wide range of surgical interventions because of its efficacy, simplicity of administration, and the availability of newer anesthetic agents with reduced side effects1. Alongside it provides attenuation of the physiological stress response to surgery, reduction in intraoperative blood loss and decreased incidence of venous thromboembolism , and improved perioperative outcomes, particularly in high- risk patients.2 Spinal anesthesia (SA) is the technique of choice for lower segment cesarean sections(lscs) , as it reduces the risk of complications such as pulmonary aspiration, airway management difficulties, and the potential adverse effects of general anesthetic agents on the fetus.³ However following SA administration, maternal hypotension and bradycardia may occur due to sympathetic inhibition combined with parasympathetic dominance, leading to a decrease in systemic vascular resistance, cardiac output, and venous return.4 Maternal hypotension may be prevented by strategies such as fluid preloading or coloading. However, in recent years, the use of pharmacological agents has gained preference. The administration of vasopressors in the management of spinal anesthesia-induced hypotension helps mitigate the effects of sympathetic blockade, there by maintaining maternal hemodynamic stability, minimizing nausea and vomiting, and preserving utero-placental perfusion without compromising fetal well-being5 Recent studies suggest that ondansetron, a selective 5-hydroxytryptamine-3 (5-HT3) receptor antagonist commonly used as antiemetic may also play a role in stabilizing hemodynamic changes induced by spinal anesthesia.6 By inhibiting the Bezold–Jarisch reflex (BJR), ondansetron reduces the incidence of spinal anesthesia- induced hypotension (SIH)7 . Various studies have evaluated the effect of different doses of ondansetron on maternal hypotension8. Therefore, the aim of this study is to evaluate the effect of administering 8 mg IV ondansetron versus placebo before spinal anesthesia in attenuating post-spinal hypotension in patients. Purpose of study is to find out whether using ondansetron 8mg IV is effective in preventing hypotension following spinal anaesthesia in elective caesarean section patients, by comparing with placebo. Aim of study is to evaluate the effect of administration of ondansetron 8mg IV versus placebo before spinal anaesthesia in attenuation of post spinal hypotension in patients of elective lscs. Primary Objectives were to determine the difference in fall of systolic blood pressure SBP (in mm Hg), diastolic pressure (DBP in mm Hg), mean arterial pressure(MAP) and heart rate (HR) between both groups and to determine difference in dose of ephedrine requirement in (mg) in both groups. Secondary objectives was to observe any side effects. Eligibility Criteria: Inclusion Criteria: Adult Patients (18 to 35 years) who gave informed written consent and belonging to ASA grade II, posted for elective lscs. Exclusion Criteria: Patients who were part of any other study, non-co-operative patient, patient having contraindications to neuraxial anaesthesia, having history of drug abuse or addictions , allergic to ondansetron or local anaesthetics, and contraindication to regional anaesthesia, were excluded from this study.

Study Design: A Prospective Interventional Double Blind Comparative Study. Sample Size: A sample size of 174 (87ineach group) was required at 95% confidence interval and 80% power to verify the expected difference of 7.4mg (+17.4) mmhg in systolic blood pressure after administration of IV onadanstron and spinal anaesthesia. Study Groups- The study was conducted with two groups of patients, each consisting of 87 participants: A. Group A (n=87): Received 10 mL of normal saline, administered 5 minutes before spinal anesthesia. B. Group B (n=87): Received 8 mg IV ondansetron diluted in 6mL of 0.9% normal saline (NS) to make a total of 10 mL, administered 5 minutes before spinal anesthesia. RANDOMIZATION Patients were randomly allocated into two groups using a simple random technique with opaque sealed envelopes. A total of 174 envelopes were prepared, each indicating a specific study group. A colleague selected an envelope, and the patient was assigned to the corresponding group. BLINDING The anesthesiologist preparing the drug was different from the one administering it and recording the parameters. The volume of the administered drug was the same in both groups to maintain blinding. PROCEDURE Following approval from the Institutional Ethics Committee, a prospective, randomized, double-blind interventional study was conducted on 174 patients which are ASA Grade II parturients aged 18–35 years, with gestational age beyond 37 weeks, scheduled for elective cesarean section. Informed written consent was obtained from all participants after a detailed pre-anesthetic evaluation. Patients fasted for 8 hours preoperatively. On the day of surgery, an 18-gauge intravenous cannula was inserted, and each patient received 50mg of intravenous ranitidine and 10 mg of intravenous metoclopramide one hour prior to entering the operating room. Before spinal anesthesia, patients were preloaded with Ringer’s lactate solution at 10 mL/kg, baseline hemodynamic parameters were recorded in the supine position, and the study drug was administered five minutes before induction. Spinal anesthesia was administered at the L3– L4 interspace using a 25-gauge Quincke needle in the sitting position, with 2 mL (10 mg) of 0.5% hyperbaric bupivacaine injected over 12–15 seconds. Sensory blockade was assessed bilaterally by the pinprick method at one-minute intervals, and motor blockade was evaluated using the Modified Bromage Scale. Surgery commenced after achieving a T6 sensory level. Hemodynamic parameters including systolic, diastolic, and mean arterial pressures (SBP, DBP, MAP), heart rate (HR), and oxygen saturation (SpO2) were recorded at baseline, at one-minute intervals for the first five minutes, every five minutes for the next 30 minutes, and subsequently every 10 minutes until the end of surgery. Hypotension (SBP < 90 mmHg or > 20% decrease from baseline) was managed with 6mg intravenous Ephedrine as required, while bradycardia (HR< 50 bpm) was treated with 0.6 mg intravenous atropine. Nausea, vomiting, and shivering were monitored; shivering was treated with 25 mg intravenous tramadol. The total ephedrine dose administered was documented for each patient. Outcome Variables 1. Changes in intraoperative hemodynamic parameters (mean SBP, mean DBP, MAP, HR) following spinal anesthesia. 2. Difference in the mean total dose of IV ephedrine (mg) required to manage hypotension. 3 Incidence of side effects (nausea, vomiting, shivering) between the two groups Statistical Analysis Data was entered into MS Excel. Continuous data was summarized using mean and standard deviation, and differences between two means were analyzed using the Student’s t-test. Categorical data was expressed as proportions, and differences in proportions were analyzed using the Chi-square test. A 95% confidence level was maintained for all statistical analyses

Patients in both groups were comparable in demographic profile, which included age, height, weight and body mass index. Comparison of number of patients having hypotension in both groups Hypotension was significantly more common in Group A (54.02%) than in Group B (26.44%) (p=0.0002). These results suggest a notable difference in physiological response to spinal anesthesia, despite similar demographic and clinical characteristics between the groups, as shown in Table 1. Table 1: Comparison of Hypotension Hypotension Group A Group B P-value No. of patients Percentage No. of patients Percentage Present 47 54.02 23 26.44 0.0002 Absent 40 45.98 64 73.56 Total 87 100.00 87 100.00 Comparison of haemodynamic parameters As shown in Figure 1, preoperatively, systolic blood pressure (SBP) was similar in both groups (129.26 ± 9.1 vs. 129.62 ± 7.29 mmHg, p=0.7). After spinal anesthesia, SBP declined more in Group A from 1 to 20 minutes (p<0.001 at 1 and 2 minutes, p=0.001 at 3 and 5 minutes, p=0.03 at 15 minutes and p=0.01 at 20 minutes). From 25 minutes onward, SBP stabilized with no significant differences (p>0.05), indicating a transient but greater early drop in SBP. As shown in Figure 2, both groups experienced a DBP drop post-spinal anesthesia, with no difference at 0 min. However, Group A had significantly lower DBP at 1 minute (p=0.01), at 5 minutes (p=0.0002), 20 minutes (p=0.03), and 25 minutes (p=0.002). From 30 minutes onward, DBP was comparable, indicating a more pronounced early decline in Group A. Preoperative MAP was similar between groups. After spinal anaesthesia, MAP declined slightly in both groups. From 1 to 25 minutes, Group A had significantly lower MAP. At 1 minute (p<0.0001), 5 minutes (p=0.0003), and 25 minutes (p=0.0003). After 30 minutes, MAP was comparable in both groups, as evident in Figure 3. There was no significant difference in HR recordings between both groups. Distribution of patients according to ephedrine dose As shown in Table 2, a total of 47 patients in Group A and 24 patients in Group B received ephedrine, and the difference was statistically significant (p=0.03). A significantly higher proportion of patients in Group B received a 6 mg dose of ephedrine (58.33%) compared to Group A (40.43%), with a p-value of 0.03, indicating statistical significance. Group A had a broader distribution of ephedrine doses, with 29.79% receiving 12 mg, 12.77% receiving 18 mg, and smaller proportions requiring even higher doses (up to 30 mg). These findings suggest that Group A had a greater need for higher doses of ephedrine to manage hypotension, as compared to Group B. Table 2: Distribution of patients according to Ephedrine Dose Ephedrine Dose Group A Group B P-value No. of patients Percentage No. of patients Percentage 6 mg 19 40.43 14 58.33 0.03 10 mg 2 4.26 0 0.00 12 mg 14 29.79 10 41.67 18 mg 6 12.77 0 0.00 20 mg 3 6.38 0 0.00 24 mg 1 2.13 0 0.00 30 mg 2 4.26 0 0.00 Total 47 100.00 24 100.00 Comparison of complications in both the groups Complications like nausea, vomiting, bradycardia and shivering were also observed. Nausea and vomiting were more common in Group A (13.79%) compared to Group B (6.90%). Bradycardia was recorded in only one patient from Group A, and there was no shivering in any of the patients in either group. The difference in the rate of complications was not significant between the two groups (p=0.77).

Spinal anaesthesia is frequently associated with hypotension, leading to maternal complications such as nausea, vomiting, dizziness, and bradycardia, as well as foetal risks like reduced uteroplacental perfusion and acidosis9. This study aims to assess the effectiveness of intravenous ondansetron (8 mg) compared to placebo in preventing post- spinal hypotension in parturients undergoing caesarean section. A significantly higher incidence of hypotension was observed in Group A compared to Group B (p = 0.0002). Similar findings were reported by Maharshi et al.10, who demonstrated a lower incidence of hypotensioninpatientsadministered6mgand 12 mg of ondansetron compared to those receiving normal saline (p = 0.04). Likewise, Wang Q et al. observed a significant reduction in maternal hypotension among patients given 4 mg and 6 mg of ondansetron compared to the control group (p < 0.05). 11 In the present study, preoperative heart rate (HR) did not differ significantly between the groups. These findings are consistent with those of Hasan M et al., who reported no significant HR variation (p > 0.05), and Wang Q et al., who observed overall HR stability except for a mild increase in the 6 mg ondansetron group. 11,12 In the present study, preoperative systolic blood pressure (SBP) did not differ significantly between the groups. However, GroupAdemonstratedasignificantdeclinein SBP from 1 to 20 minutes following spinal anesthesia (p < 0.05), while values beyond 25 minutes remained comparable. Nath et al. reported similar findings, noting significant SBP reductionsat 10,15, and 30 minutesafter subarachnoid block (p < 0.001). 13 Nausea and vomiting were observed more frequently in Group A, with one instance of bradycardia and no episodes of shivering in either group. Nonetheless, the overall incidence of complications did not reach statistical significance (p = 0.77). Correspondingly, Nath et al. documented a significant decrease in hypotension (p <0.001) but found no significant variation in the incidence of shivering (p = 0.066) or bradycardia (p = 0.149). 13

Although the demographic and clinical characteristics were similar between the groups, patients in Group B, who received 8 mg of intravenous ondansetron, experienced significantly lower incidences of hypotension and required less fluid resuscitation following spinal anesthesia compared to Group A. Additionally, Group A required higher doses of ephedrine. Early decreases in systolic, diastolic, and mean arterial pressures were more pronounced in Group A, indicating greater hemodynamic instability. Whilenauseaandvomitingoccurredmorefrequently in Group A, the overall rate of complications did not differ significantly between thegroups.Theseresultshighlight thepotentialof ondansetron in attenuating earlyhemodynamic fluctuations associated with spinal anesthesia.

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