Intranasal Ketamine for Acute Traumatic Pain

Intranasal Ketamine for Acute Traumatic Pain in the Emergency Department: A Prospective, Randomized Clinical Trial of Efficacy and Safety

Introduction: Ketamine has been well studied for its efficacy as an analgesic agent. However, intranasal (IN) administration of ketamine has only recently been studied in the emergency setting.

Objective: To elucidate the efficacy and adverse effects of a sub-dissociative dose of IN Ketamine compared to IV and IM morphine.

Methods: A single-center, randomized, prospective, parallel clinical trial of efficacy and safety of IN ketamine compared to IV and IM morphine for analgesia in the emergency department (ED). A convenience sample of 90 patients aged 18-70 experiencing moderate-severe acute traumatic pain (≥80mm on 100mm Visual Analog Scale [VAS]) were randomized to receive either 1.0mg/kg IN ketamine, 0.1mg/kg IV MO or 0.15mg/kg IM MO. Pain relief and adverse effects were recorded for 1 hour post-administration.

Primary Outcomes: The primary outcome was efficacy of IN ketamine compared to IV and IM MO, measured by "time-to-onset" (defined as a ≥15mm pain decrease on VAS), as well as time to and degree of maximal pain reduction.

Study Overview

• Status: Completed
• Conditions: Acute Pain
• Intervention / Treatment: Drug: Ketamine Hydrochloride; Drug: Morphine

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Tel Aviv, Israel
    • Tel Aviv Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients aged 18-70 years, with mild to moderate blunt trauma (sustained in road, workplace and home accidents) causing moderate to severe pain (≥ 80mm score on a 100mm Visual Analog Scale=VAS) were eligible for participation in the study. Inclusion criteria also included a Glasgow Coma Score (GCS) of 15, body weight of 50-110 kg, systolic blood pressure of 90-160 mmHg, heart rate <100 bpm. Patients were also required to have an American Society of Anesthesiologists (ASA) score of 1 or 2, deny head injury, and deny regular use or use of opiates.

Exclusion Criteria:

Any analgesia received within the prior 3 hours, allergic sensitivity to morphine or ketamine, a large meal ingested within the previous hour, pregnancy, deviated nasal septum or trauma to the nose, and a history of a psychiatric condition. Despite evidence that ketamine does not exacerbate intracranial hemorrhage in patients with head trauma, patients with head injury complaining of loss of consciousness, dizziness, vomiting, or nausea were excluded as well.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IN Ketamine; A single administration of 1 mg/kg ketamine hydrochloride delivered in an intranasal route using an atomizer	Drug: Ketamine Hydrochloride; Delivered intranasally using an atomizer
Active Comparator: IM Morphine; A single administration of 0.15 mg/kg intramuscular morphine	Drug: Morphine; Delivered either as an IM injection or a slow IV bolus
Active Comparator: IV Morphine; A single administration of 0.1 mg/kg slow intravascular bolus of morphine.	Drug: Morphine; Delivered either as an IM injection or a slow IV bolus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness of intranasal ketamine in decreasing pain intensity [patient assessed - VAS pain score]	Time to achieve a clinically meaningful pain reduction was defined as the first time-point at which the patient reported 15mm of pain reduction or more. Maximal pain reduction was defined as the lowest VAS score reported by the patient over the course of follow-up. Time to maximal pain reduction was defined as the time at which the patient has the lowest VAS score over the course of the hour follow-up.	1 hour post administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse effects [Opiate Related Symptom Distress Scale]	Adverse effects were recorded at the end of one hour using the 'Opiate Related Symptom Distress Scale' and included measurements of the presence, frequency, intensity and disruptiveness of 12 common opiate side-effects. Among these were nausea, vomiting, urinary retention, constipation, difficulty concentrating, dizziness, confusion, and others.	1 hour post administration
patient satisfaction [Interview]	patients were asked to provide subjective comments	1 hour post administration

Collaborators and Investigators

• Sponsor: Tel Aviv Medical Center
• Investigators: Principal Investigator: Pinchas Halpern, MD, Tel Aviv Medical Center

Publications and helpful links

General Publications

• Shimonovich S, Gigi R, Shapira A, Sarig-Meth T, Nadav D, Rozenek M, West D, Halpern P. Intranasal ketamine for acute traumatic pain in the Emergency Department: a prospective, randomized clinical trial of efficacy and safety. BMC Emerg Med. 2016 Nov 9;16(1):43. doi: 10.1186/s12873-016-0107-0.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: June 27, 2016
• First Submitted That Met QC Criteria: June 27, 2016
• First Posted (Estimate): June 29, 2016

Study Record Updates

• Last Update Posted (Estimate): June 30, 2016
• Last Update Submitted That Met QC Criteria: June 29, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Intranasal Ketamine, Analgesia, Trauma, Morphine, Mass Casualty
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; 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, Opioid; Narcotics; Ketamine; Morphine
• Other Study ID Numbers: 0312-11-TLV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO