Low-dose Ketamine for Acute Pain in the Emergency Department

Benefit of the Association of Low Doses of Ketamine With Intravenous Morphine in the Treatment of Acute Severe Pain in Emergency Department

This study aims to determine the efficacy and safety of low dose ketamine in association with IV morphine in the management of acute moderate to severe pain in emergency department.

The investigators hypothesize that low dose ketamine will result in more effective pain control than morphine alone and will not be associated with an increase in adverse events.

Study Overview

• Status: Unknown
• Conditions: Pain
• Intervention / Treatment: Drug: Morphine; Drug: Ketamine; Drug: Placebos

Detailed Description

Management of pain in the Emergency Department is challenging. Treatment of pain is most often accomplished by parenteral opioids analgesics. However, the use of opioids alone for pain control is often associated with inadequate analgesia and increased adverse events.

Low-dose ketamine has been shown to improve pain perception and produce an opioid-sparing effect when given perioperatively.

Its use in the ED may probably play a role in maximizing analgesia.

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 1

Contacts and Locations

Study Locations

• Tunisia
  • Sousse, Tunisia, 4002
    • Faculty of medicine of Sousse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Able to understand and give informed consent
• Comfortable with the experimental protocol as outlined to them by the research team
• Severe pain, pain score of at least 50/100 on Visual Analogue Scale (VAS) or 5/10 numerical ratings score
• Acute pain, pain duration < 7days
• Deemed by treating ED attending physician to require IV opioid analgesia

Exclusion Criteria:

• Neurologic, respiratory, or hemodynamic compromise
• Pregnancy or breastfeeding
• Known or suspected allergy to ketamine or morphine
• Known Renal (Cr>2.0) or Liver Failure
• Unstable psychiatric disease (as per treating physician)
• History of stroke
• History of cardiac disease or coronary artery disease
• History of chronic respiratory disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Morphine and Placebo; Morphine IV, Dose: 0.1 mg/Kg followed 10 minutes later by an injection of Placebos (0.9% normal saline 0.05ml/kg)	Drug: Morphine; Morphine; Other Names: Morphine Sulfate; Drug: Placebos; 0.9% normal saline; Other Names: Normal Saline Flush, 0.9% Injectable Solution
Experimental: Morphine and Ketamine 0.15; Morphine IV, Dose: 0.1 mg/Kg followed 10 minutes later by an IV bolus of Ketamine at the dose of 0.15mg/kg	Drug: Morphine; Morphine; Other Names: Morphine Sulfate; Drug: Ketamine; ketamine; Other Names: Ketalar, 50 Mg/mL Injectable Solution
Experimental: Morphine and Ketamine 0.3; Morphine IV, Dose: 0.1 mg/Kg followed 10 minutes later by an IV bolus of Ketamine at the dose of 0.3mg/kg	Drug: Morphine; Morphine; Other Names: Morphine Sulfate; Drug: Ketamine; ketamine; Other Names: Ketalar, 50 Mg/mL Injectable Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of analgesia: To assess the primary outcome of pain relief, we used patient-reported pain scores. We consider the pain decreasing of at least 50% of pain score and the summed pain-intensity difference (SPID) over 2 hours	At baseline, to assess our primary aim, efficacy of pain control, we will use patient reported pain scores and amount of rescue analgesia (parenteral morphine) received. Trained residents will ask participants to report their pains scores using a numerical pain rating scale (NPRS). The NPRS used will be a 0 to 10 rating scale. Baseline NPRS will be measured after randomization, but just before administration of morphine. Change in reported pain score during the protocol will be analysed. The SPID was calculated using the pain-intensity difference (PID) at each of these study time points. The PID for a given time point is equal to the baseline NPRS minus the subsequent NPRS at each study time point. SPID is the summation of the PID at each of the study time points, weighted using the amount of time since the prior assessment	Two hours after starting protocol

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total patient-perceived pain relief	The total patient-perceived pain relief will be calculated using weighted sum of the pain relief scale performed at each study time point. This pain relief scale is a five-point scale that asks participants to rate pain relief as complete = 4, a lot = 3, some = 2, a little = 1, and none = 0	Two hours after starting protocol
Amount of rescue analgesia received	The amount of rescue analgesia received (in milligrams of morphine equivalents) will be recorded.	Two hours after starting protocol
Time to rescue analgesia	Time to rescue analgesia will be calculated as the time from administration of the last study medication (placebo or ketamine) to administration of an opioid analgesic.	Two hours after starting protocol
The occurrence of adverse events	We will record participant-reported dizziness, nausea, vomiting, confusion, dysphoria, visual disturbances, or other complaints at baseline and each study time point. All patients will be monitored for the duration of the study period and vital signs will be recorded at each time point. The presence of tachycardia (heart rate > 100 beats/min.), hypotension (systolic blood pressure [sBP] < 100 mm Hg), hypertension (sBP > 180 mm Hg or diastolic blood pressure [dBP] > 100 mm Hg), and respiratory depression (respiratory rate < 12 breaths/min, oxygen saturation < 92%, or need for supplemental oxygen) will be noted.	Two hours after starting protocol
The total dose of morphine administered	The amount of rescue analgesia will be recorded at each time point and the total dose calculated	Two hours after starting protocol

Collaborators and Investigators

• Sponsor: Faculty of Medicine, Sousse
• Investigators: Principal Investigator: Hajer KRAIEM, MD, Faculty of medicine of Sousse

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): June 1, 2016
• Study Completion (Anticipated): March 1, 2017

Study Registration Dates

• First Submitted: January 9, 2017
• First Submitted That Met QC Criteria: January 9, 2017
• First Posted (Estimate): January 11, 2017

Study Record Updates

• Last Update Posted (Estimate): January 31, 2017
• Last Update Submitted That Met QC Criteria: January 29, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: pain; emergency; morphine; ketamine; analgesia
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Emergencies; 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; Pharmaceutical Solutions; Morphine
• Other Study ID Numbers: FMSousse

Plan for Individual participant data (IPD)

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