One of the most popular and widely used methods of anesthesia is spinal anesthesia. It is a fast, low-cost, and efficient way to provide postoperative analgesia while totally compromising motor and sensory function. Spinal anesthesia is not risk-free, even though it has long been seen to be a safe procedure. Spinal anesthesia is known to cause hypotension, nausea, and vomiting as adverse effects [1-2]. Depending on the type and dosage of the anesthetic used, spinal anesthesia can cause alterations in the respiratory, neurological, and cardio-circulatory systems. Unwanted effects can thus be prevented with approaches that allow limit anesthetic to be operated with more diluted and lower solution doses only in the field. While the preferred technique for surgeries on the lower extremities is spinal anesthesia [3–4]. Preserving the safety of both mother and child is the main goal of obstetric anesthesia. As a result, choosing the anesthetic and how to administer it correctly are crucial. Spinal anesthetic is now the drug of choice for cesarean sections since it is straightforward and has little effect on the fetus [5–6]. Spinal anesthetic induces unpleasant effects even though it is ideal for cesarean sections. When a puerperium exhibits unstable hemodynamics, spinal anesthesia may result in severe bradycardia or hypotension [7]. One medication used to prevent postoperative nausea and vomiting (PONV) is ondansetron, which selectively inhibits the 5-HT3 receptors to have an antiemetic effect [8]. Due to its capacity to inhibit the BJ reflex, ondansetron was consequently recommended as a treatment strategy to prevent hypotension in patients receiving spinal anesthesia [9–10]. According to several research, ondansetron is advantageous for obstetric patients in this regard [9–12]. Ondansetron's preventive use in preventing hypotension following spinal anesthesia in non-obstetric patients has, however, only been the subject of a small number of trials [13–14]. Ephedrine is a sympathomimetic that primarily maintains arterial pressure by raising cardiac output (CO) and heart rate. It also has an indirect mechanism of action (releasing norepinephrine) through direct agonist activity on α-and β-receptors [15–16]. Because it is impossible to estimate when ephedrine will peak and how much of it will be absorbed systemically, the prophylactic administration of ephedrine by intramuscular route is contentious [17]. Because prophylactic ephedrine has a longer half-life than other vasopressors, it can be safely given by bolus intravenous (IV) injection, which is also inexpensive and easy to administer [18]. In order to prevent arterial hypotension following a cesarean section, a bolus IV injection of ephedrine is more beneficial than an infusion [19]. Therefore, the current work was aimed to revealed the preoperative ondansetron and ephedrine requirements during spinal anesthesia for cesarean sections

Patients 

Each patient participated in the study gave given written consent after receiving approval from the scientific research committees at the Faculty of Medicine and the Deanship of Scientific Research at the University of Diyala. This research is a single-blind, randomized clinical experiment. From April 2023 to April 2020, the study was conducted in Al-Shifa Private Hospital in Baqubah, Diyala.The current study includes the total number of 135 pregnant women who were scheduled to have a caesarian section under spinal anesthesia.

Study groups 

The current study comprised a total of 135 pregnant women who were scheduled for a caesarian section under spinal anesthesia; these women were randomly assigned to three equal groups, 

• Group N was given 10 milliliters of 0.9% normal saline, either with or without ephedrine, as a control. 

• Group E was given 10 mg of ephedrine diluted to 10 mL in 0.9% normal saline. 

• Group O received ondansetron 8 mg, either with or without ephedrine, diluted to 10 mL in 0.9% normal saline. 

• Inclusion criteria

Al-Shifa Private Hospital - Baqubah / Diyala planned elective cesarean deliveries under spinal anesthesia for patients with singleton pregnancies at 37 weeks or more completed.

Exclusion criteria

The exclusion criteria included weight exceeding 130 kg, use of blood or colloid fluids during surgery, hypertension, gestational hypertension, other cardiovascular diseases, physical status III or higher according to the American Society of Anesthesiologists, and use of steroids or adrenergic agonists during pregnancy.

Procedure 

Patients are managed in the ways listed below. The day before the procedure, they were assessed in the anesthetic clinic. On the morning of the procedure, the participants' informed agreement was obtained, and they were given an intravenous infusion of 500 milliliters of lactated ringer's solution. Following their transfer to the operating room, patients were monitored using an electrocardiogram, and pulse oximetry. Prior to the start of the surgery, the mean arterial pressure and pulse rate were monitored. After administering spinal anesthetic while sitting at the L3–L4 or L4–L5 level using a 27-gauge Quincke spinal needle, 2.5 mL (12.5 mg) of 0.5% hyperbaric bupivacaine was given intrathecally. After that, the patient was placed supine on the operating table with their uterus displaced 15 degrees to the left of their body. Prior to surgery, heart rate and mean arterial pressure were measured every five minutes.  A drop in MAP less than 65 was referred to as hypotension. If hypotension occurred, intravenous ephedrine 5–10 mg was administered, and intravenous atropine 0.5 mg was used to treat bradycardia, which was defined as PR <50 beats/min. Before delivery, the degree of nausea and/or vomiting was scored using the following four-point grading system: 0 indicates no symptoms, 1 nausea, 2 vomiting once or twice, and 3 vomiting more than twice. Patients who complained of nausea or vomiting were given 10 mg of metoclopramide intravenously. Apgar scores at one and five minutes, as well as the total amount of IV fluid given, were noted.

Statistical analysis 

Software from SPSS was used for statistical analysis (version 20). Extracted data were shown as mean ± SD unless specified differently. The mean drop in SBP for each group was analyzed using an independent sample t-test. An independent sample t-test was used to compare the demographic data (mean ± SD) between the two groups. Number needed to treat, percentage, and Chi-square testing were used as necessary to compare the outcome measures. 95% confidence intervals were provided for all quantitative characteristics.

Comparable mean values for age, height, weight, and gestation week were found in the demographic data of the three groups. The three groups' surgical times, spinal anesthesia to delivery times, and APGAR scores at one and five minutes were also similar (Table 1).

Table (1): the demographic data in the three groups

*GN: normal saline group          OG: ondansetron group        EG: ephedrine group

Systolic blood pressure measurements from the study and control groups were compared in Table 2. According to time the systolic blood pressure readings of ondansetron group were 119.48±5.12, 111.35±3.37, 109.42±3.67, 113.52±4.45, 124.38±3.52 mmHg as baseline, 5, 10, 15 and 20 minutes, whereas, the readings in ephedrine group were, 121.05±3.52, 103.13±3.31, 91.16±4.51, 101.7±5.13, 118.93±4.53 mmHg as baseline, 5, 10, 15 and 20 minutes, as shown in table 3.1. At the baseline reading, there was no significant difference (P > 0.05); however, after five, ten, and fifteen minutes, the ephedrine group's systolic blood pressure significantly decreased, and after twenty minutes, the three groups' levels equalized (P > 0.05). The results were not statistically different (P > 0.05) after 20 minutes, thus those readings were not recorded.

Table (2): Systolic blood pressure in study groups

*GN: normal saline group          OG: ondansetron group        EG: ephedrine group

The diastolic blood pressure measurements for the study and control groups were compared in Table 3. According to time the diastolic blood pressure readings of ondansetron group were 82.4±5.93, 81.8±3.14, 81.2±3.29, 80.4±4.11, 82.1±3.37 mmHg as baseline, 5, 10, 15 and 20 minutes, whereas, the readings in ephedrine group were, 82.4±2.37, 77.2±4.21, 74.9±5.55, 71.3±3.18, 79.5±3.15 mmHg as baseline, 5, 10, 15 and 20 minutes, as shown in table 3.1. the diastolic blood pressure was considerably lower in the ephedrine group at 5, 10, and 15 minutes, and the level was equalized across the three groups at 20 minutes (P>0.05). However, there was an insignificant difference at the baseline measurement. The results were not statistically different (P > 0.05) after 20 minutes, thus those readings were not recorded.

Table (3): Diastolic blood pressure in study groups

*GN: normal saline group          OG: ondansetron group        EG: ephedrine group

During a cesarean section performed under spinal anesthesia, phenylephrine and ephedrine are administered to treat maternal hypotension [20–21]. In contrast to other research [22–23], which utilized a combination of vasopressors (ephedrine and phenylphrine), our study only used ephedrine, which offers greater consistency. This was a randomized controlled experiment with single-term parturients who got prophylactic ephedrine, ondansetron, or placebo and underwent spinal anesthesia for an elective cesarean delivery. Different doses of preventive intravenous ondansetron were explored by Meng et al. [24] in order to prevent hypotension after cesarean delivery. They discovered that the ideal dose for prophylactic ondansetron during cesarean delivery was 4 mg. Numerous investigations conducted by Walid Trabelsi et al. [26] and Sahoo et al. [25] demonstrated that prophylactic intravenous Ondansetron 4 mg administered prior to subarachnoid block decreased the need for vasopressors and hypotension in parturients undergoing elective cesarean sections. We therefore administered an ondansetron dose of 4 mg to the study group, and the results of these investigations were consistent with the findings of the present investigation. Comparing the Ondansetron 8mg group to the control saline group, the study conducted by Owczuk R et al [10] found that the reduction in mean blood pressure was lessened. According to Syed and Ezzat [27], older individuals' incidence of hypotension and bradycardia can be reduced by intravenous dose of 8 mg of Ondansetron given five minutes before subarachnoid block.

The study and control groups' heart rate values were compared in Table (4). The ondansetron group's heart rate measurements according to time were 89.4±8.28, 73.1±4.45, 64.3±4.21, 81.8±5.04, 88.2±8.15 beat / minutes as baseline, 5, 10, 15 and 20 minutes, whereas, Table 4 displays the baseline values for the ephedrine group, which were 91.2±4.93, 85.7±4.14, 76.5±5.29, 89.2±6.11, and 90.5±7.37 beats per minute at 5, 10, 15, and 20 minutes. At the baseline reading, there was no significant difference (P > 0.05); however, after five, ten, and fifteen minutes, the heart rate in the ondansetron group was considerably lower, and after twenty minutes, the three groups' levels were equal (P > 0.05). Readings after 20 minutes were not recorded because they were not statistically different after that time (P > 0.05).

Table (4): Heart rate in study groups

*GN: normal saline group          OG: ondansetron group        EG: ephedrine group

Ephedrine is a beneficial drug for treating hypotension brought on by lower systemic vascular resistance or decreased cardiac output because it has been demonstrated to raise heart rate, cardiac output, and blood pressure [28]. Table 4 demonstrates how ephedrine affects heart rate, which is consistent with findings from Giuliano et al. [29], who found that ephedrine raises blood pressure and heart rate by raising cardiac output and systemic vascular resistance. Comparable to our research, Owczuk et al. [10] Compared to the control saline group, ondansetron 8 mg had no effect on heart rate.

Table 5 shows that shivering was seen in 3(2.2%), 6(4.4%) subjects in Ondansetron and ephedrine group respectively and 14(10.4%) subjects in saline group (P=0.041). The three groups also did not differ significantly in view of pain and bradycardia (P>0.05). Nausea and vomiting was significantly more in saline group (15.6%) as compared to ephedrine (9.6%) and Ondansetron group (3.0%), (P=0.001). Bradycardia was significantly more in saline group (3.0%) as compared to ephedrine (1.5%) and Ondansetron group (0.0%), (P=0.071). Ephedrine was required significantly more in saline group (14.1%) and as compared to Ondansetron group (1.5%), (P=0.001).

Table (5): Other complications in study groups

*GN: normal saline group          OG: ondansetron group        EG: ephedrine group

According to the latest data, during a cesarean section performed under spinal anesthesia, the Ondansetron group experienced a lower incidence of bradycardia, nausea, and vomiting than the placebo group. showed the need for ephedrine was decreased and the number of hypotensive episodes with intravenous Ondansetron. Arivumani et al., however, found that intravenous ondansetron 4 mg considerably lowers hypotension [30]. Additionally, they discovered that the Ondansetron group experienced lower bradycardia episodes and needed lower vasopressors. Prophylactic Ondansetron was shown by Walid et al. [26] to dramatically lower the incidence of hypotension in healthy parturients having spinal anesthesia during elective cesarean sections. The role of intravenous Ondansetron in preventing bradycardia and hypotension was investigated by Tubog et al. [31]. Many techniques, including as preloading with intravenous fluids, planning patients to promote venous return, and administering vasopressors, are employed to lower the incidence of hypotension and bradycardia. Administering pharmacologic medications such as Ondansetron prophylactically is an additional approach that may prove to be more efficacious than simply staying hydrated [32–33].

From the results of this study, we were able to determine that, in comparison to a placebo, ondansetron lowers the requirement for ephedrine during the procedure. Maternal blood pressure, heart rate, shivering, nausea, and vomiting are significantly affected by prophylactic ephedrine 10 mg or ondansetron 8 mg given right after spinal anesthesia for an elective cesarean delivery.

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