Does Higher OT Temperature and IV Ondansetron Reduce Incidence of PSS in Parturients?

Phase 4

• Conditions: Chills; Tremor; Nausea, Postoperative; Vomiting, Postoperative; Temperature Change, Body; Postoperative Shivering
• Interventions: Drug: IV Ondansetron 4mg; Drug: Placebo; Other: Higher OT temperature range; Other: Lower OT temperature Range

• Registration Number: NCT04654429
• Lead Sponsor: Dr Lim Siu Min

Brief Summary

This study will look at the incidence of post-spinal shivering (PSS) among the obstetrics population and will investigate whether higher operation theater (OT) temperature range or/and IV Ondansetron are able to reduce the incidence of PSS. This is a double-blind, randomized, factorial study, patients will be grouped into 4 groups - LP, HP, LO, HO (L= low-temperature range, H= high-temperature range, P= placebo, O=Ondansetron). All patients undergoing cesarean section under spinal anesthesia will be recruited, and it will be conducted in obstetrics OT.

Detailed Description

Many studies have been conducted to look at methods to prevent and treat postspinal shivering. However, there is still no clear protocol or gold standard for post-spinal shivering management. This is due to the fact that post-spinal shivering mechanisms are complex and are broadly grouped into thermoregulatory and non-thermoregulatory. Preventive measures that have been studied are broadly classified into pharmacological methods and non-pharmacological methods. For Non-pharmacological method, active warming of the patient by various methods have been found to be effective in preventing PSS. However, there is no study that looks at ways to reduce heat loss hence maintaining normothermia and preventing PSS in patients. Therefore in this study, we will be investigating if higher OT temperature will reduce the incidence of PSS. As for pharmacological methods, many drugs have been studied for examples analgesics (tramadol), opioid receptor agonists (pethidine, fentanyl), cholinesterase inhibitors (physostigmine), N-methyl-D-aspartate receptor antagonists (ketamine, magnesium sulphate), α2-central agonists (clonidine, dexmedetomidine), antiserotonergic (ondansetron) and anti-inflammatory drugs (dexamethasone). Ondansetron is usually used to prevent chemotherapy or radiotherapy-induced nausea vomiting and Post-operative nausea and vomiting. Due to the fact that it is generally a safe drug and has added benefit as an anti-emetics especially for obstetrics population, this drug is chosen to be studied. We will also look at the efficacy of the combined effect of increased OT temperature and prophylaxis ondansetron on preventing PSS.

Study Timeline

• Study Start: 2020-10-13
• Study First Submitted: 2020-11-11
• Study First Submitted QC: 2020-11-28
• Study First Posted: 2020-12-04
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-12
• Last Update Posted: 2021-10-14
• Primary Completion: 2022-12-30
• Study Completion: 2022-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 628

Inclusion Criteria

• All elective and emergency obstetric patients who are going for lower segment caesarean section (LSCS) under spinal anaesthesia in UMMC.
• Patient who are given combined spinal epidural anaesthesia (CSE) without epidural local anaesthetic top-up will be included.

Exclusion Criteria

1. Patients who refused to provide study consent
2. Caesarean section planned under general or epidural anaesthesia or potential conversion to general anaesthesia intraoperatively
3. Royal College of Obstetrics and Gynaecology (RCOG) classification of urgency caesarean section Grade I - Immediate threat to life of woman and child. (29)
4. Patients with psychiatric disorders who are taking selective serotonin reuptake inhibitor (SSRI) and serotonin-noradrenaline reuptake inhibitor (SNRI)
5. Patients who has problems with any types of tremor or involuntary movements and neuromuscular disorders such as Parkinson Disease and muscular dystrophy will be excluded from the study as this will interfere with the clinical interpretation of shivering
6. Patients with history of allergic / hypersensitive reactions towards ondansetron.
7. Patients who received ondansetron intraoperatively as anti-emetics.
8. Recruited patients will be excluded if OT temperature on the day of recruitment does not fulfil the OT temperature range fixed for the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Lower OT temperature with IV Ondansetron 4mg (LO)	IV Ondansetron 4mg	Lower OT temperature with Ondansetron 4mg intravenous. This group also will receive one pharmacological intervention, which is IV ondansetron 4mg to prevent incidence of PSS under standard OT temperature 17-19 degrees.
higher OT temperature 19-22 and IV ondansetron 4mg (HO)	IV Ondansetron 4mg	This group will receive 2 interventions - higher OT temperature 19-22 and IV ondansetron 4mg. This group is designed to see if when both intervention combined, will further reduce the incidence of PSS among obstetrics population.
Lower OT temperature with placebo (LP)	Placebo	Lower OT temperature with placebo This group function as a main control arm. Incidence of PSS will be documented usual / standard OT temperature which is 17-19 degree celsius, and without giving any pharmacological intervention to prevent PSS.
Lower OT temperature with IV Ondansetron 4mg (LO)	Lower OT temperature Range	Lower OT temperature with Ondansetron 4mg intravenous. This group also will receive one pharmacological intervention, which is IV ondansetron 4mg to prevent incidence of PSS under standard OT temperature 17-19 degrees.
Higher OT temperature with placebo (HP)	Placebo	Higher OT temperature with placebo This group will receive one non-pharmacological intervention, which is higher OT temperature 19-22 degree celsius. The aim of this intervention is to reduce heat loss therefore incidence of PSS for obstetric population coming for lower segment cesarean section (LSCS) by reducing the temperature gradient between the body and environment.
Lower OT temperature with placebo (LP)	Lower OT temperature Range	Lower OT temperature with placebo This group function as a main control arm. Incidence of PSS will be documented usual / standard OT temperature which is 17-19 degree celsius, and without giving any pharmacological intervention to prevent PSS.
Higher OT temperature with placebo (HP)	Higher OT temperature range	Higher OT temperature with placebo This group will receive one non-pharmacological intervention, which is higher OT temperature 19-22 degree celsius. The aim of this intervention is to reduce heat loss therefore incidence of PSS for obstetric population coming for lower segment cesarean section (LSCS) by reducing the temperature gradient between the body and environment.
higher OT temperature 19-22 and IV ondansetron 4mg (HO)	Higher OT temperature range	This group will receive 2 interventions - higher OT temperature 19-22 and IV ondansetron 4mg. This group is designed to see if when both intervention combined, will further reduce the incidence of PSS among obstetrics population.

Primary Outcome Measures

Name	Time	Method
To Demonstrate higher OT temperature range ( 19.1- 22.0 degree Celcius) is effective in reducing the incidence PSS in parturients.	1 year	Assessment of patient's shivering grade according to Crossley and Mahajan classification in both Higher temperature range group ( 19.1 -22.0 degree Celcius) compared to lower OT temperature range group (17.0 - 19.0 degree Celcius) Grade 0 - No Shivering Grade 1 - No visible muscle activity, but one or more of piloerection , peripheral vasoconstriction or peripheral cyanosis ( other causes excluded) Grade 2 - Muscular activity in only one muscle group Grade 3 - Moderate muscle activity in more than one muscle group but not generalised shaking Grade 4 - Violent muscular that involves the entire body
To demonstrate IV Ondansetron is effective in reducing the incidence of PSS in parturient undergoing LSCS.	1 year	Assessment of patient's shivering grade according to Crossley and Mahajan classification in both patients receiving placebo group vs receiving Ondansetron group: Grade 0 - No Shivering Grade 1 - No visible muscle activity, but one or more of piloerection , peripheral vasoconstriction or peripheral cyanosis ( other causes excluded) Grade 2 - Muscular activity in only one muscle group Grade 3 - Moderate muscle activity in more than one muscle group but not generalised shaking Grade 4 - Violent muscular that involves the entire body

Secondary Outcome Measures

Name	Time	Method
To determine the incidence of PSS	1 year	Number patients of with shivering grade 3 and above.
To determine the average threshold body temperature, ⁰C at which shivering occur.	1 year	To determine the average range of temperature that grade 3 and above shivering occurred among the recruited population from linear graph
To determine if higher OT temperature range with IV Ondansetron (HO group) is superior to individual intervention alone in reducing the incidence of PSS	1 year	Assessment of patient's shivering grade according to Crossley and Mahajan classification
To determine the change in body temperature (mean δ Temp ⁰C) at which shivering occur	1 year	To assess average temperature drop in order for shivering to occur from linear graph

Trial Locations

Locations (1)

University Malaya Medical Center; 🇲🇾 Kuala Lumpur, Malaysia