Pain Clinical Trial
Official title:
Low Dose Ketamine Versus Morphine for Moderate to Severe Pain in the Emergency Department: A Prospective, Randomized, Double-Blind Study
The primary objectives of the study are to evaluate the efficacy of subdissociative dose intravenous ketamine compared with intravenous morphine in relieving acute pain in the ED. Secondary objectives will include the rate of adverse effects and need for rescue analgesia. The hypothesis is that intravenous administration of subdissociative dose ketamine at 0.3 mg/kg is superior to intravenous morphine at 0.1mg/kg in treating moderate and severe acute pain in patients presenting to the ED.
Rationale: Opioids are traditionally accepted as a cornerstone of acute pain management in
the Emergency Department (ED). Morphine is one of the most commonly used parenteral opioid
analgesics whose initial dose of 0.1 mg/kg has been extensively researched and recommended
for control of severe acute pain in the ED. However, intravenous administration of opioids
is associated with thefollowing side effects: hypotension, respiratory depression,
dizziness, pruritis and nausea. In addition, in patients with pre-existing renal and/or
hepatic insufficiency, these effects may be pronounced and require interventions. Thus, the
administration of an equipotent analgesic that does not cause hypotension and respiratory
depression would enhance patient safety in the ED.
Ketamine is a noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist that blocks the
release of excitatory neurotransmitter glutamate and provides anesthesia, amnesia and
analgesia by virtue of decreasing central sensitization and "wind-up" phenomenon. Due to its
high lipid solubility, ketamine rapidly crosses the blood-brain barrier, provides rapid
onset of action (peak concentration at is reached 1 minute after IVP) and rapid recovery to
baseline (duration of action 5-15 minutes after IVP) (1). When given at subdissociative
doses of 0.1-0.5 mg/kg, either as an adjunct to opioid analgesic or as a solo agent,
ketamine provides good analgesia while preserving airway patency, ventilation, and
cardiovascular stability (2). In addition, a small dose of ketamine may increase the
analgesic potency of opioids thus decreasing their dosing requirements (3). Based on the
aforementioned facts, ketamine offers an attractive option for providing safe and convenient
pain control for patients in the ED.
A double-blind trial of 40 adult patients with acute musculoskeletal trauma compared
low-dose ketamine administered by subcutaneous infusion (0.1 mg/kg/h) with intermittent
intravenous morphine (0.1 mg/kg IV every 4 hours ) and demonstrated better pain relief, less
sedation and less nausea and vomiting with ketamine infusion than with intermittent
morphine. In addition, none of the patients in the ketamine group required supplementary
analgesia (4). A prospective, randomized trial compared two analgesic regimens, morphine
with ketamine (K group) or morphine with placebo (P group) for severe acute pain in 73
trauma patients with a visual analog scale (VAS) score of at least 60/100. Morphine was
administered at 0.1mg/kg; patients in the K group received 0.2 mg/kg of intravenous ketamine
over 10 minutes while patients in the P group received isotonic sodium chloride solution.
The results showed comparable change in VAS score at 30 minutes (34 mm (K) vs. 39 mm (P))
but reduced morphine consumption in the ketamine group (0.14 mg/kg (K) vs 0.2 mg/kg (P))
(5).
A chart review analysis of 35 ED patients receiving low dose ketamine at doses
0.1mg-0.6mg/kg in addition to intravenous morphine demonstrated a decrease in pain intensity
for 54% of the patients by a documented 3 point pain decrease on a 10-point scale. The
ketamine doses ranged from 5 mg to 35 mg with median dose of 10 mg and mean dose of 15.7mg.
In addition, only one patient had a brief dysphoric reaction that did not require
intervention (6).
Hypothesis: Intravenous administration of subdissociative dose ketamine at 0.3 mg/kg is
superior to intravenous morphine at 0.1 mg/kg in treating moderate and severe acute pain in
patients presenting to the ED.
Methods: Prospective, randomized, double-blind trial evaluating and comparing analgesic
effect of intravenous Ketamine administered in sub-dissociative doses: 0.3 mg/kg given over
10 minutes with intravenous Morphine given at 0.1mg/kg as a single IVP.
Description: Once patient is triaged, an initial pain score will be assessed and patient's
stated weight will be recorded in the chart. Patients will then have an initial evaluation
by an attending ED physician and once found to be eligible for the study (deemed by treating
physician to warrant administration of intravenous analgesia) patient will be randomized to
receive either morphine at 0.1 mg /kg given as IVP or ketamine at 0.3 mg/given as IVP.
Patients' vital signs will be recorded at triage, at the beginning of the study and at 15,
30, 60, 90, 120 minutes post-administration. Patients will be placed on a monitor and
continuous pulse oximetry (oxygen saturation), blood pressure, heart rate and respiratory
rate will be recorded. We will compare efficacy as a difference between 2 groups in pain
relief from the baseline (at triage) to 30 minutes post-analgesic administration. The
primary outcome is the difference between 2 groups in pain relief at 30 minutes. The
secondary outcome is side effects. We will compare the safety profile of each analgesic with
respect to incidence of hypotension, respiratory depression, nausea and vomiting, pruritis,
need for an opioid reversal agent (naloxone), tachycardia, laryngospasm, hypersalivation,
dizziness, agitation and need for benzodiazepines (midazolam) administration for symptomatic
evidence of emergence reaction. All the data will be entered and analyzed via SPSS. Data
analyses will include frequency distributions, and ANOVA to assess a difference in pain
scores between the groups at various time points. All patients will be analyzed with an
intent to treat analysis. However, a subgroup analysis will be done for any emergence
reaction or event which occurs often.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT05559255 -
Changes in Pain, Spasticity, and Quality of Life After Use of Counterstrain Treatment in Individuals With SCI
|
N/A | |
Completed |
NCT04748367 -
Leveraging on Immersive Virtual Reality to Reduce Pain and Anxiety in Children During Immunization in Primary Care
|
N/A | |
Terminated |
NCT04356352 -
Lidocaine, Esmolol, or Placebo to Relieve IV Propofol Pain
|
Phase 2/Phase 3 | |
Completed |
NCT05057988 -
Virtual Empowered Relief for Chronic Pain
|
N/A | |
Completed |
NCT04466111 -
Observational, Post Market Study in Treating Chronic Upper Extremity Limb Pain
|
||
Recruiting |
NCT06206252 -
Can Medical Cannabis Affect Opioid Use?
|
||
Completed |
NCT05868122 -
A Study to Evaluate a Fixed Combination of Acetaminophen/Naproxen Sodium in Acute Postoperative Pain Following Bunionectomy
|
Phase 3 | |
Active, not recruiting |
NCT05006976 -
A Naturalistic Trial of Nudging Clinicians in the Norwegian Sickness Absence Clinic. The NSAC Nudge Study
|
N/A | |
Completed |
NCT03273114 -
Cognitive Functional Therapy (CFT) Compared With Core Training Exercise and Manual Therapy (CORE-MT) in Patients With Chronic Low Back Pain
|
N/A | |
Enrolling by invitation |
NCT06087432 -
Is PNF Application Effective on Temporomandibular Dysfunction
|
N/A | |
Completed |
NCT05508594 -
Efficacy and Pharmacokinetic-Pharmacodynamic Relationship of Intranasally Administered Sufentanil, Ketamine, and CT001
|
Phase 2/Phase 3 | |
Recruiting |
NCT03646955 -
Partial Breast Versus no Irradiation for Women With Early Breast Cancer
|
N/A | |
Active, not recruiting |
NCT03472300 -
Prevalence of Self-disclosed Knee Trouble and Use of Treatments Among Elderly Individuals
|
||
Completed |
NCT03678168 -
A Comparison Between Conventional Throat Packs and Pharyngeal Placement of Tampons in Rhinology Surgeries
|
N/A | |
Completed |
NCT03286543 -
Electrical Stimulation for the Treatment of Pain Following Total Knee Arthroplasty Using the SPRINT Beta System
|
N/A | |
Completed |
NCT03931772 -
Online Automated Self-Hypnosis Program
|
N/A | |
Completed |
NCT02913027 -
Can We Improve the Comfort of Pelvic Exams?
|
N/A | |
Terminated |
NCT02181387 -
Acetaminophen Use in Labor - Does Use of Acetaminophen Reduce Neuraxial Analgesic Drug Requirement During Labor?
|
Phase 4 | |
Recruiting |
NCT06032559 -
Implementation and Effectiveness of Mindfulness Oriented Recovery Enhancement as an Adjunct to Methadone Treatment
|
Phase 3 | |
Active, not recruiting |
NCT03613155 -
Assessment of Anxiety in Patients Treated by SMUR Toulouse and Receiving MEOPA as Part of Their Care
|