Granisteron Versus Ondansetron for Prophylaxis Against Post-Spinal Anesthesia Shivering: a Randomized Controlled Study

3. Scientific committee approval (Was it scientifically approved by the department?) Yes

Date of approval: Sunday ,1ST September,2019

Background and Rationale:

Regional anesthesia is commonly associated with intraoperative shivering which reaches 40-60%. Spinal anesthesia contributes in impairment of thermoregulation, and predisposes patients to hypothermia, which reduces the threshold for shivering and vasoconstriction. Other mechanisms responsible for shivering include increased sympathetic tone, pain, and systemic release of pyrogens. Shivering causes increase in metabolic activity, oxygen consumption, intracranial, and intraocular pressure. Shivering is also responsible for increasing cardiac output, peripheral resistance, carbon dioxide production, and lactic acidosis. Furthermore, shivering interferes with electrocardiogram (ECG) and pulse oximetry. 1 Post anaesthetic shivering is one of the most frequent problems in the early recovery phase following general anaesthesia. It was considered as the sixth most important problem of current clinical anaesthesiology among 33 low morbidity clinical outcomes. Previous studies have found that shivering occurs up to 60% of patients in the postoperative period and varies according to sex, age, drugs used for anaesthesia and the duration for the surgery.2 Since shivering is a response to hypothermia, body temperature should be maintained within 36.5-37.5°C, however, shivering may be also seen in normothermic patients undergoing regional anesthesia. A number of factors responsible for developing of hypothermia in regional anesthesia including age, level of sensory block, temperature of the operating room and infusion solution.3 Perioperative hypothermia and shivering can be prevented by physical methods like surface warming or pharmacologically by drugs such as pethidine, tramadol, clonidine, doxapram, opioids, neostigmine, magnesium sulfate and ketamine.4 Pethidine is the most commonly used drug for post spinal anesthesia shivering. The disadvantage of pethidine is that it can cause respiratory depression in the presence of previously administered opioids or anaesthetics. Moreover, hypotension, nausea and vomiting are also important side effect of pethidine.5 Pethidine, which is considered as a time-tested drug for control of shivering, can have adverse effects such as respiratory depression, nausea, and vomiting. which begs to investigate the efficacy of other drugs.6 5-HT antagonists had been effectively introduced for management of perioperative shivering by inhibiting thermoregulatory response by central mechanism. Ondansetron is a 5-HT antagonist which had been effectively used in treatment of postoperative shivering.7 Granisteron, a new generation of 5-HT antagonists, had been also reported effective in the prevention of Postoperative shivering.9-10 No data are available about the comparison of both drugs, ondansetron and granisteron, for prophylaxis against post-spinal shivering The aim of the investigator's study is to compare the efficacy of granisteron to ondansetron for prevention of intra- and post spinal anaesthesia shivering.

Study Overview

• Status: Unknown
• Conditions: Spinal Anaesthetic
• Intervention / Treatment: Drug: Ondansetron 8mg

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 12566
    • Kasr Alainy medical school

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • With ASA physical status I and II

  • Scheduled to undergo lower half surgery under spinal anesthesia such as lower limb orthopedic surgeries, lower limb plastic surgeries, or lower abdominal surgeries.

Exclusion Criteria:

• • Patient refusal

  • Patients with age above 60 years and below 18 years.
  • Pregnant
  • Patients with contraindications to spinal anesthesia
  • Preoperative fever or hypothermia (temperature >38°C or below 36.5°C), hypo or hyperthyroidism, a requirement for blood or blood product transfusion during surgery and medications likely to alter thermoregulation or nausea and vomiting, will be excluded.
  • Patients with significant cardiopulmonary disease (i.e. ejection fraction <40% and/or SpO2 < 92% on room air) or psychological disorder
  • impaired renal (serum creatinine > 2 mg/dL) or hepatic function (class B or C on Child-Pugh score)
  • Procedures with anticipated duration less than 90 minutes or more than 180 min, those received saddle block or those required vasodilator administration
  • Allergy to any of the study drugs will be excluded from the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Granisteron group	Drug: Ondansetron 8mg; Study drugs will be prepared, diluted to a volume of 10 mL using saline 0.9%
ACTIVE_COMPARATOR: Ondansetron group	Drug: Ondansetron 8mg; Study drugs will be prepared, diluted to a volume of 10 mL using saline 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
perioperative spinal induced shivering	incidence of shivering during spinal anaesthsia	during spinal anaesthesia

Secondary Outcome Measures

Outcome Measure	Time Frame
incidence of perioperative nausea and vomiting	during spinal anaethesia

Collaborators and Investigators

• Sponsor: Kasr El Aini Hospital

Publications and helpful links

General Publications

• Nallam SR, Cherukuru K, Sateesh G. Efficacy of Intravenous Ondansetron for Prevention of Postspinal Shivering during Lower Segment Cesarean Section: A Double-Blinded Randomized Trial. Anesth Essays Res. 2017 Apr-Jun;11(2):508-513. doi: 10.4103/aer.AER_26_17.
• Iqbal A, Ahmed A, Rudra A, Wankhede RG, Sengupta S, Das T, Roy D. Prophylactic granisetron vs pethidine for the prevention of postoperative shivering: a randomized control trial. Indian J Anaesth. 2009 Jun;53(3):330-4.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): April 1, 2020
• Primary Completion (ANTICIPATED): September 1, 2020
• Study Completion (ANTICIPATED): September 1, 2020

Study Registration Dates

• First Submitted: March 2, 2020
• First Submitted That Met QC Criteria: March 3, 2020
• First Posted (ACTUAL): March 4, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 4, 2020
• Last Update Submitted That Met QC Criteria: March 3, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: 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: MS-265-2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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