Comparison of weight-adjusted dose versus fixed dose ondansetron in Prevention of shivering following spinal anaesthesia for caesarean deliveries

Shivering is an inadvertent muscle tissue activity influencing muscle or more muscle groupes. It is a natural reflex that causes muscle contractions to increase body heat production. Spinal anaesthesia had been demonstrated to be an excellent regional technique recommended in almost 86% of caesarean sections. ¹

The incidence of shivering ranging from 40%-64% % after neuraxial anaesthesia. ²

During caesarean sections, shivering is an obvious topic of concern for pregnant women which has been shown to exacerbate wound pain and anguish and disrupt with wound healing by straining the incisions. Shivering also raises energy expenditure and metabolic processes by 40–120%. It causes tachycardia and hypertension, as well as an increase in cardiac output, by stimulating catecholamine outflow. ³

Shivering has been linked to an increase the incidence of maternal and subsequently fetal hypoxemia and maternal myocardial activity with limited oxygen supply causing myocardial ischemia. Shivering occasionally raises intra-ocular and intracranial tension, which is a concern for an anesthesiologist because it interferes with blood pressure monitoring and causes antiques in ECG and pulse oximetry. ⁴

By transferring heat from the core to the peripheral thermal compartment, where the majority of it is lost to the environment, spinal anesthesia-induced vasodilation contributes to dermal heat loss. Core temperatures drop by 0.5°C to 1°C above the level of the spinal block after neuroaxial anaesthesia is achieved, causing vasoconstriction and shivering.⁵

Some medications have been shown to be effective in preventing shivering after general anaesthesia. However, few studies have been conducted on parturient women who had caesarean procedures. Tramadol, pethidine, nalbuphine, and clonidine were once used to treat perioperative shivering, however the significant adverse effects of these drugs prevent anesthesiologists from administering them before birth, potentially endangering the foetus and mothers.^{6, 7}

Ondansetron, a 5-HT3 receptor antagonist, could be used safely during pregnancy for anti-nausea and anti-emetic action. There was no evidence of a danger or an increase in unfavourable foetal development outcomes in pregnant women who were taken ondansetron during gestation. Ondansetron has also been used to prevent and control nausea and vomiting during surgery, as well as to decrease opioid-caused itching during regional anaesthesia. Ondansetron has a good therapeutic index, which means it has relatively minimal side effects even at large doses, including the elimination and treatment of chemotherapy-related nausea and vomiting. Constipation, headaches, and malaise/fatigue are all common complaints. Hypertension and tachycardia are caused by rapid administration.^8,9,10

The dose-dependent antishivering effect of ondansetron is weight-dependent, with low-dose ondansetron (4mg) being found to be equally effective as high-dose ondansetron (8mg) in 50kg patients. ¹⁰

Shivering would be treated with ondansetron during general and regional anaesthesia.  perShivering drugs act by adjusting central core temperature, whereas 5-HT antagonists, such as ondansetron, can aid with operative shivering . The precise mechanism could be that serotonin reuptake in the anterior hypothalamic preoptic area is inhibited. Heat generation and heat loss pathways may be influenced by 5-HT3 receptors. ¹¹

Ondansetron has been used to treat shivering during caesarean delivery while under spinal anaesthetic in a few studies. There has never been a study that looked at different doses of ondansetron to prevent shivering after spinal anaesthesia. ¹¹

The study compared the efficacy of a prophylactic weight-adjusted and fixed dose of ondansetron against that of a synthetic opioid in pursuit of a safer and more reliable prescription (Pethidine, which is the gold standard drug for shivering controle). The purpose of this study was to compare the efficacy, potency, haemodynamic effects, and complications or side effects of a fixed dose of ondansetron (4 mg) versus a weight-adjusted dose of ondansetron (0.1 mg/kg) in suppressing pethidine-related shivering as a control, as well as the degree of shivering between groups after caesarean sections under spinal anaesthesia. A secondary goal is to reduce adverse effects such as headaches and haemodynamic fluctuations.

PATIENTS AND METHODS

A double-blind, prospective, randomised control trial was used as the study design.

It was studied at Al-Azhar University's Medicine Faculty in Cairo, Egypt, from May 2020 to February 2021, after being approved by the Ethics and Scientific Committee. The study included 129 healthy pregnant women between the ages of 21 and 35 who were scheduled for elective caesarean delivery under spinal anaesthetic at Al-Azhar University Hospitals (Al- Hussein and Bab al- Shaaria) in Cairo, Egypt.

Participants were recruited after signing a written informed consent form indicating their willingness to engage in a research project and the confidentiality of their personal information. They would get the same quality of care as all other patients in the operating room and would not be denied medicines in order to deny participation in the trial. The patient was informed about the study protocol both orally and in writing. Despite the fact that the patient receives no direct benefit from participating in the study, the findings may be used to influence future local practise. They could also leave the study at any time and continue to receive standard care.

Patients who met either of the following criteria were excluded from the study:

1. Ondansetron or pethidine can be given before surgery.

2. Ondansetron or pethidine allergy

3. Shivering occurs before spinal anaesthesia.

4. Premature labour, antepartum haemorrhage, a history of hyperemesis gravidarum, pregnancy-induced toxaemia, and other complications of pregnancy

Sample-size calculation;

The MedCalc® version 12.3.0.0 programme "Ostend, Belgium" was used for sample size measurements, as was a statistical calculator based on a 95 % confidence interval and a 5 % error 80 % analysis power. A previous research (Gicheru et al., 2019)12 found shivering was higher in the intervention group (11.3%) than in the control group (22.6 % ). Thus, it could be used in this research; based on these values, a sample size of 108 cases was calculated; however, to identify such a variation, the sample size was determined in the entire study group to 135 cases, However, six patients met the exclusion criteria, leaving 129 patients who participated in the study and were assigned equally using a computer programme. Subdivided into three;

Group I (43 cases); ondansetron 4mg (FDO).

Group II (43 cases); 0.1mg/kg dose-adjusted (WAO).

Group III (43 cases); 1 mg/kg pethidine (PC).

The test drugs were prepared in identical 10 ml syringes by an anesthesiologist who did not participate in any other aspect of the study, syringes labelled with the active drug of the study were again packed in an opaque envelope to the same code as the randomly selected patient.

Upon admission to the operating theatres, cardiovascular baseline parameters were assessed via automated non-invasive blood pressure measurement, electrocardiography, and pulse oximetry. Core temperature had been measuered also by the monitor as part of the baseline parameters (GE Healthcare Finland model B40i).

All patients received 15ml/kg solution at ambient temperatur

by spinal  midline approach  administered at the L3/L4 interspace with a 25 French gauge Quincke Type point (B/BRAUN, Spinocan) needle following a 2ml 2% local Lidocaine solution. 2mls of bupivacaine and 20ug fentanyl were administered after free fluid flow (CSF). Till repositioning the patient supine having 15 degrees left lateral slope,   that one was administered immediately after spinal anaesthesia. (The first group (FDO) received a fixed dose of 4 mg of ondansetron, the second group (WAO) a weight-adjusted dose of 0.1 mg/kg, and the third group (control group) received 0.5 mg/kg of pethidine, each prepared in 10 ml syringes.

Surgery began when the sensory block reached the reported target level.

Preoperative hemodynamic data (mean blood pressure and heart rate) were gathered 15, 30, 45, 60, 90, and 120 minutes after spinal anaesthesia.

Temporal thermometer fluctuations were recorded at intervals of 15, 30, 45, 60, 90, and 120 minutes.

A four-point Bedside Shivering Assessment Scale for measuring shivering (BSAS) was established and validated for two hours following spinal anaesthesia whenever shivering occurred; cases of shivering above grade 3 or causing discomfort were treated with i.v. pethidine 40 mg;

0= indicates there's no shivering.

1= Slight face/neck fasciculation.

2= Tremor in many muscle groups.

3=Extensive all-body shivering.

RESULTS

The following tables and figures illustrate the findings of this research.

There were no statistically significant differences between groups in terms of demographic data, as seen in table (1).

Table 1: Demographic data

P-value>0.05 NS, the mentioned data expressed as Mean±SD.

There was no statistically significant difference in spinal block level between classes, as illustrated in figure 1 and table 2.

Fig. 1: Spinal block level.

Table 2: Spinal block level

The mentioned data expressed as median and range H=Kruskal Wallis,

P-value>0.05 NS

Regarding heart rate, although there was a small rise in pulse rate in the pethidine group as compared to the other groups, but the difference was not statistically important, as seen in Table (3) and figure (2).

Table 3: Heart rate (beat/min)

The mentioned data expressed in Mean±SD.

Fig. 2: Heart rate (beat/min).

The mentioned data expressed in Mean±SD.

As regard to blood pressure, in all groupes, there was a slight decline in mean arterial blood pressure (mmhg) values at 30 minutes to 60 minutes interval, but it was not statistically important, as seen in table(4) and figure (3).

Table 4: Mean arterial blood pressure (mmHg) changes; Data expressed as Mean±SD.

Fig. 3: Mean arterial blood pressure (mmHg) changes.

AS regard to body temperature, the three groups had equal temperatures prior to spinal anesthesia. The three groups experienced a steady decline in temperature that began at 30 minutes and peaked at 120 minutes. The control group (PC) had seen a greater decrease in core temperatures. This is shown in the following table 5 and figure 4.

Table 5: Temperature changes; P-value>0.05 NS; *p-value <0.05, a: significant difference with group I (Fixed dose of ondansetron), b: significant difference with group II (Weight Adjusted ondansetron).

Fig. 4: Temperature changes (^oc).

There were no statistically important differences in the duration of surgery between the groups. As seen in Table 6, shivering was found in 13 patients (30.2 %) in the first group (FDO), 11 patients (25.6 %) in the second group (WAO), and 11 patients (25.6 %) in the third group (PC), all of whom complained of grade I shivering, but there was no statistically significant difference between the groups. In contrast to the second group (WAO), the magnitude of shivering (grade II) was greater in the first group (FDO) (11.6 %) 5 patients (7.0 % ) 3 patients, as regard to the start of shivering This table illustrates a statistically significant difference between groups. Shivering was maximally delayed in the control group (after 39.27±3.35 minutes), earlier in the first group FDO (after 29.92±7.68 minutes), and began later in the WAO group (after 33.55±4.76 minutes). Shivering duration was significantly longer in the (FDO) group than in the (WAO) group, with the shortest time in the (PC) group. As shown in Table 6 and Figures 5 and 6, respectively.

Table 6: Using: F-One Way Analysis of Variance; x²: Chi-square test

Post HOC test: LSD: a: significant difference with group I (Fixed dose of ondansetron); b: significant difference with groupII (Weight Adjusted ondansetron)

P-value >0.05 NS; *p-value