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

Does Higher Operation Theatre Ambient Temperature and Intravenous Ondansetron Prophylaxis Reduce Incidence of Post-spinal Shivering in Obstetric Population? A Double-blind, Randomised, Factorial Study.

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Anticipated): 628
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: SIU MIN LIM, L; Phone Number: 6017-7337750; Email: limsiumin@gmail.com
• Study Contact Backup: Name: Tsyr Xiang Teoh, M; Phone Number: 6017-4540608; Email: tsyrxiang@gmail.com

Study Locations

• Malaysia
  • Kuala Lumpur, Malaysia, 50603
    • Recruiting
    • University Malaya Medical Center
    • Contact: SIU MIN LIM, L; Phone Number: 6017-7337750; Email: limsiumin@gmail.com
    • Contact: Tsyr Xiang Teoh, M; Phone Number: 6017-4540608; Email: tsyrxiang@gmail.com
    • Principal Investigator: SIU MIN LIM, L
    • Sub-Investigator: SOOK HUI CHAW, AP
    • Sub-Investigator: CAROLYN YIM CHUE WAI, AP
    • Sub-Investigator: JAUHARATUNNUR ISHAK, M
    • Sub-Investigator: TSYR XIANG TEOH, M

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Lower OT temperature with placebo (LP); 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.	Drug: Placebo; IV Normal Saline 2cc will be given; Other Names: Control; Other: Lower OT temperature Range; OT temperature set to 17-19 degree celsius; Other Names: Control
ACTIVE_COMPARATOR: Higher OT temperature with placebo (HP); 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.	Drug: Placebo; IV Normal Saline 2cc will be given; Other Names: Control; Other: Higher OT temperature range; OT temperature set to 19-22 degree celsius; Other Names: Non-pharmacological intervention
ACTIVE_COMPARATOR: Lower OT temperature with IV Ondansetron 4mg (LO); 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.	Other: Lower OT temperature Range; OT temperature set to 17-19 degree celsius; Other Names: Control; Drug: IV Ondansetron 4mg; IV ondansetron 4mg; Other Names: Pharmacological intervention
ACTIVE_COMPARATOR: higher OT temperature 19-22 and IV ondansetron 4mg (HO); 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.	Other: Higher OT temperature range; OT temperature set to 19-22 degree celsius; Other Names: Non-pharmacological intervention; Drug: IV Ondansetron 4mg; IV ondansetron 4mg; Other Names: Pharmacological intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Demonstrate higher OT temperature range ( 19.1- 22.0 degree Celcius) is effective in reducing the incidence PSS in parturients.	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	1 year
To demonstrate IV Ondansetron is effective in reducing the incidence of PSS in parturient undergoing LSCS.	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	1 year

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Dr Lim Siu Min
• Investigators: Principal Investigator: SIU MIN LIM, L, MALAYA UNIVERSITY; Study Director: SOOK HUI CHAW, AP, MALAYA UNIVERSITY; Study Director: CAROLYN YIM CHUE WAI, AP, MALAYA UNIVERSITY; Study Chair: JAUHARATUNNUR ISHAK, M, MALAYA UNIVERSITY; Study Chair: TSYR XIANG TEOH, M, MALAYA UNIVERSITY

Publications and helpful links

General Publications

• Crowley LJ, Buggy DJ. Shivering and neuraxial anesthesia. Reg Anesth Pain Med. 2008 May-Jun;33(3):241-52. doi: 10.1016/j.rapm.2007.11.006.
• Choi KE, Park B, Moheet AM, Rosen A, Lahiri S, Rosengart A. Systematic Quality Assessment of Published Antishivering Protocols. Anesth Analg. 2017 May;124(5):1539-1546. doi: 10.1213/ANE.0000000000001571.
• Horn EP, Schroeder F, Gottschalk A, Sessler DI, Hiltmeyer N, Standl T, Schulte am Esch J. Active warming during cesarean delivery. Anesth Analg. 2002 Feb;94(2):409-14, table of contents. doi: 10.1097/00000539-200202000-00034.
• Alfonsi P. Postanaesthetic shivering. Epidemiology, pathophysiology and approaches to prevention and management. Minerva Anestesiol. 2003 May;69(5):438-42.
• Varshney RK, Garg M, Kapoor K, Jheetay GS. The role of ramosetron in the prevention of post-spinal shivering in obstetric patients. A prospective randomized double blind study. Rom J Anaesth Intensive Care. 2019 Apr;26(1):37-43. doi: 10.2478/rjaic-2019-0006.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 13, 2020
• Primary Completion (ANTICIPATED): December 30, 2022
• Study Completion (ANTICIPATED): December 30, 2022

Study Registration Dates

• First Submitted: November 11, 2020
• First Submitted That Met QC Criteria: November 28, 2020
• First Posted (ACTUAL): December 4, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 14, 2021
• Last Update Submitted That Met QC Criteria: October 12, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: temperature; caesarean section; ondansetron; obstetrics; Subarachnoid block; Post-spinal shivering; factorial study
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Signs and Symptoms, Digestive; Nausea; Vomiting; Postoperative Nausea and Vomiting; Body Temperature Changes; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Ondansetron
• Other Study ID Numbers: NMRR-20-2158-56283; 202073-8861 (OTHER: MREC UMMC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All volunteers identity will be kept anonymous. However demographic data, body biometrics, underlying co-morbidities, indications for cesarean section, and study outcomes will be analysed and tabulated for publication purposes.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No