Low Dose Ketamine for Management of Acute Severe Pain in the Emergency Department

This study aims to address both the management and evaluation of pain. The primary aim of this study is to determine the efficacy of low dose ketamine in adults with moderate to severe pain in the emergency department as compared with parenteral opioids alone. Another aim is to examine the safety of low dose ketamine compared to opioids alone.

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: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Ketamine 0.15mg/kg; Drug: Ketamine 0.3mg/kg; Other: Placebo

Detailed Description

Management and assessment of pain in the Emergency Department (ED) can be challenging. Treatment of pain is most often accomplished by parenteral opioids analgesics. However, inadequate analgesia is often a problem when opioids alone are relied on for pain control. In the peri-operative setting ketamine has been used as an adjunct to opioids for acute pain. Ketamine may play a role in maximizing analgesia in the ED.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital

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:

• English speaking
• Adults age 18-65
• 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
• ASA (American Society of Anesthesiologists) class I or II

Exclusion Criteria:

• Previously enrolled in the study
• Neurologic, respiratory, or hemodynamic compromise
• GCS (Glasgow Coma Scale) <15
• Pox <94%, RR <10, or RR >22
• SBP <90, SBP>180, or DBP >110
• Discretion of treating physician
• Pregnancy or breastfeeding
• Known or suspected allergy to ketamine or morphine
• Ketamine within 24 hours of presentation (prescription or illicit drugs)
• Conscious sedation in ED (per treating physician), includes ketamine (for non-study purposes)
• Known Renal (Cr>2.0) or Liver Failure
• Unstable psychiatric disease (as per treating physician)
• History of stroke
• History of cardiac disease
• Prior myocardial infarction; Angina (Stable or Unstable)
• Cardiac stents or bypass surgery

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
Experimental: LDK1: Low dose Ketamine (0.15mg/kg); Participants randomized to the first group, LDK1, will receive an intravenous injection of low dose ketamine (0.15mg/kg). All participants, regardless of the group, will receive a dose of morphine(0.15mg/kg) at the same time the study drug is administered.	Drug: Ketamine 0.15mg/kg; 0.15mg/kg ketamine delivered IV (in the vein) following clinician assessment in ER. Number of cycles: until discharge or 6 hours elapses.; Other Names: Ketamine
Experimental: LDK2: Low dose Ketamine (0.3mg/kg); Participants randomized to the second group, LDK2, will receive an intravenous injection of low dose ketamine (0.3mg/kg). All participants, regardless of the group, will receive a dose of morphine(0.15mg/kg) at the same time the study drug is administered.	Drug: Ketamine 0.3mg/kg; 0.3 mg/kg ketamine delivered IV (in the vein) following clinician assessment in ER. Number of cycles: until discharge or 6 hours elapses.; Other Names: Ketamine
Placebo Comparator: 0.9% Normal Saline; This group will receive a placebo injection of 0.9% normal saline of a similar volume (0.05ml/kg)	Other: Placebo; Placebo injection of 0.9% normal saline of a similar volume (0.05ml/kg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in reported pain score at 15 minutes, 30 minutes, and hourly for 6 hrs or until discharge	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 research assistants (RA) 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: a rating of 0 corresponds to "no pain at all," whereas a rating of 10 is the "worst pain imaginable." Baseline NPRS will be measured after randomization, but just before administration of ketamine or placebo injection and morphine (Baseline). Repeat measurements will be taken at 15 minutes, 30 minutes, and hourly following treatment with the study drug, for 6hrs or until the patient leaves the ED. The amount of rescue analgesia will be recorded at each time point. The ED course will also be reviewed post hoc by the RAs and physician investigators to confirm analgesia received. The main outcome measure will be the change in pain score over time.	Between patient arrival and patient discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety--Determine the incidence of adverse events associated with ketamine and morphine, versus morphine alone at 5 minutes, 30 minutes, and hourly up to 6 hours.	Adverse events will further be defined as Hypotension (SBP < 90), Hypertension (SBP >180, or Diastolic Blood Pressure >110), Presence of nausea/vomiting, presence of hallucinations, Respiratory depression (pOx<92%, Respirator Rate<12, EtCO2 >40), and need for naloxone. All patients will be monitored continuously with cardiac telemetry, pulse oximetry, and capnography following administration of the study drug. Level of sedation will be assessed using an adaptation of the Ramsay Scoring System and the Pasero Opioid Induced Sedation Scale. (Appendix 2) Further, the ED and inpatient course will be reviewed post hoc by the RAs and physician investigators who will record: Time to inpatient admission or discharge, inpatient length of stay, time to operative intervention, outcome of admission (i.e. discharge to home, SNF, rehab) and any morbidity and mortality suffered by the patient and medical complications (myocardial infarction, respiratory infection, etc…).	15 minutes, 30 minutes, hourly up to 6 hours

Collaborators and Investigators

• Sponsor: Rhode Island Hospital
• Investigators: Principal Investigator: Francesca Beaudoin, MD, Rhode Island Hospital

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: September 26, 2012
• First Submitted That Met QC Criteria: November 29, 2012
• First Posted (Estimate): December 4, 2012

Study Record Updates

• Last Update Posted (Actual): September 7, 2022
• Last Update Submitted That Met QC Criteria: September 6, 2022
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Pain; Ketamine; Acute pain; Pain control
• 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; Ketamine
• Other Study ID Numbers: 298021