Dexmedetomidine, Ketamine and Dexmetedomidine-Ketamine Combination for Control of Shivering During Regional Anaethesia

Comparing Dexmedetomidine, Ketamine and Dexmetedomidine-Ketamine Combination to Control Shivering During Regional Anaethesia

Shivering is defined as an involuntary, repetitive activity of skeletal muscles. The incidence of shivering has been found to be quite high, approximately 40-50% in different studies. It can double or even triple oxygen consumption and carbon dioxide production. Shivering also increase intraocular and intracranial pressure, and may contribute to increased wound pain, delayed wound healing, and delayed discharge from post-anaesthetic care. Apart from being an uncomfortable experience, its deleterious effects deserve primary prevention and rapid control on occurence.

Study Overview

• Status: Completed
• Conditions: Shivering
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: ketamine; Drug: Dexmetedomidine+Ketamine

Detailed Description

Shivering is a physiological response to core hypothermia in an attempt to raise the metabolic heat production. The main causes of intra and postoperative shivering are heat loss, increased sympathetic tone, pain, and systemic release of pyrogens. Spinal anaesthesia significantly impairs the thermoregulation system by inhibiting tonic vasoconstriction, which plays a significant role in temperature regulation. It also causes a redistribution of core heat from the trunk (below the block level) to the peripheral tissues. These factors predispose patients to hypothermia and shivering.

The treatment of shivering includes both pharmacological and non-pharmacological methods. The non-pharmacological management is by external heating like the use of forced air warming, warming blankets, warmed fluids etc.

According to the results of meta-analysis, the most frequently reported pharmacological interventions include clonidine, pethidine, tramadol, nefopam, and ketamine. Unfortunately, no gold standard treatment is known for shivering as the administration of all the available drugs is associated with various adverse effects.

Dexmedetomidine, a congener of clonidine, is a highly selective adrenoceptor agonist. It has been used as a sedative agent and is known to reduce the shivering threshold. Few studies which have explored its anti-shivering potential have inferred that dexmedetomidine is an effective drug without any major adverse effect and provides good haemodynamic stability.

Ketamine has been tried to prevent shivering during anaesthesia with good results. Ketamine a competitive NMDA receptor antagonist has a role in thermoregulation at various levels. NMDA receptor modulates non-adrenergic and serotoninergic neurons in locus coeruleus. It is used as anti-shivering agent.

Shivering is a physiological response to core hypothermia in an attempt to raise the metabolic heat production. The main causes of intra and postoperative shivering are heat loss, increased sympathetic tone, pain, and systemic release of pyrogens. Spinal anaesthesia significantly impairs the thermoregulation system by inhibiting tonic vasoconstriction, which plays a significant role in temperature regulation. It also causes a redistribution of core heat from the trunk (below the block level) to the peripheral tissues. These factors predispose patients to hypothermia and shivering.

The treatment of shivering includes both pharmacological and non-pharmacological methods. The non-pharmacological management is by external heating like the use of forced air warming, warming blankets, warmed fluids etc.

According to the results of meta-analysis, the most frequently reported pharmacological interventions include clonidine, pethidine, tramadol, nefopam, and ketamine. Unfortunately, no gold standard treatment is known for shivering as the administration of all the available drugs is associated with various adverse effects.

Dexmedetomidine, a congener of clonidine, is a highly selective adrenoceptor agonist. It has been used as a sedative agent and is known to reduce the shivering threshold. Few studies which have explored its anti-shivering potential have inferred that dexmedetomidine is an effective drug without any major adverse effect and provides good haemodynamic stability.

Ketamine has been tried to prevent shivering during anaesthesia with good results. Ketamine a competitive NMDA receptor antagonist has a role in thermoregulation at various levels. NMDA receptor modulates non-adrenergic and serotoninergic neurons in locus coeruleus. It is used as anti-shivering agent.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt
    • Ghada Mohammmad Aboalfadl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• This study will include adults between 18 and 60 years of age undergo elective lower abdominal and lower limb surgery using spinal anaesthesia.
• ASA grade I - II

Exclusion Criteria:

• Patient refusal.
• Patients who have temperature over 37.3 or below 36 celsius degree.
• Known allergies to the study drugs.
• Contraindication to spinal anaesthesia as coagulopathy,
• patients with thyroid disease, Parkinson disease, dysautonomia, Raynaud syndrome, use of sedative-hypnotic agent or vasodilators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexmedetomidine; 1st group will include 30 patients will receive intravenous dexmedetomidine 1 mcg/kg.	Drug: Dexmedetomidine; 30 patients will receive intravenous dexmedetomidine 1 mcg/kg.; Other Names: precedex
Experimental: Ketamine; 2nd group will include 31 patients will receive intravenous ketamine 0.4 mg/kg.	Drug: ketamine; 31 patients will receive intravenous ketamine 0.4 mg/kg.; Other Names: katalar
Experimental: Dexmetedomidine-Ketamine combination; 3rd group will include 33 patients will receive combination between intravenous dexmedetomidine 0.5mcg/kg and low dose ketamine 0.25mg/kg.	Drug: Dexmetedomidine+Ketamine; 33 patients will receive combination between intravenous dexmedetomidine 0.5mcg/kg + low dose ketamine 0.25mg/kg.; Other Names: precedex+katalar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
shivering score	p1(frequency of number)	10 minutes

Collaborators and Investigators

• Sponsor: Assiut University

Publications and helpful links

General Publications

• Nikolic K, Popovic R. Conductometric determination of periciazine. Acta Pol Pharm. 1978;35(2):195-9. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: September 26, 2017
• First Submitted That Met QC Criteria: September 30, 2017
• First Posted (Actual): October 5, 2017

Study Record Updates

• Last Update Posted (Actual): July 3, 2018
• Last Update Submitted That Met QC Criteria: July 1, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Ketamine; Dexmedetomidine
• Other Study ID Numbers: AMMH

Drug and device information, study documents

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