Intravenous Sub-dissociative Dose Ketamine Injection Versus Infusion for Analgesia in the Emergency Department

Intravenous Sub-dissociative Dose Ketamine Injection Versus Infusion for Analgesia in the Emergency Department: A Prospective, Randomized, Double-blind Placebo Controlled Trial

Objective: The purpose of this study is to determine if administering ketamine as an intravenous (IV) infusion over 15 minutes, as compared to an IV push, will decrease adverse drug reactions without attenuating its analgesic effects.

Study design: prospective, randomized, controlled, double-blind trial.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Ketamine IV Infusion; Drug: Ketamine IV push

Detailed Description

Objective: The purpose of this randomized, controlled, double-blind trial is to evaluate if sub-dissociated dose ketamine given as an infusion versus an intravenous (IV) push over 1 minute has fewer and/or less severe adverse drug reactions and provides equivalent analgesia for patients with moderate to severe pain in the emergency department (ED).

Study design: Prospective, randomized, controlled, double-blind trial

Participants: Research assistants will recruit patients ≥18 years old with moderate to severe pain (NRS≥5) and an anticipated stay in the emergency department ≥1 hour. A sample size calculation was performed based on prior data which suggests that 60% of IV push arm and 20 % of infusion arm will have adverse drug reactions. investigators assume an alpha of 0.05 and a power of 0.8, which results in 56 patients needing to be enrolled.

Intervention: After a trained research assistant obtains written informed consent, pharmacists will randomize the participants to the IV push or IV infusion arm of the study. All patients will be placed on a cardiac monitor. All patients will receive and IV push over 1 minute and a 100 mL normal saline minibag over 15 minutes.

In the IV push arm, pharmacists will provide to the nurse ketamine 0.3 mg/kg in a 10 mL syringe and a 100 mL normal saline minibag. The nurse will start the minibag of normal saline and then administer the IV push of ketamine over 1 minute.

In the IV infusion arm, pharmacists will provide to the nurse ketamine 0.3 mg/kg in a 100 mL normal saline minibag and a 10 mL syringe of normal saline. The nurse will start the minibag of normal saline and then administer the IV push over 1 minute.

Data collection: The trained research assistant will collect data on the patients' pain scores, adverse drug reactions (presence, severity, and how bothersome they are), and vital signs.

Statistical analysis: Investigators will perform descriptive statistics, compare the proportion of patients with side effects, compare the severity of the side effects scores, and compare how bothersome the side effects.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Oakland, California, United States, 94602
      • Alameda Health System, Highland Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pain NRS ≥5
• Anticipated stay in ED ≥1 hour

Exclusion Criteria:

• Pregnant or breast feeding
• Vital sign abnormalities (SBP <90, SBP > 180, HR < 50, HR > 150, RR <10, RR > 30, weight <45 kg, weight > 115 kg)
• Arrhythmias
• Altered mental status (active psychosis/delirium)
• Administration of opioid pain medication in previous 1 hour
• history of acute head or ocular trauma
• presence of known intracranial mass or vascular lesion

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine IV infusion; Ketamine 0.3 mg/kg in 100 mL normal saline minibag infused over 15 minutes. Placebo: 10 mL normal saline in syringe pushed over 1 minute. Masking: placebo normal saline minibags and placebo syringes will appear identical to the normal saline minibus and syringes with ketamine.	Drug: Ketamine IV Infusion; Ketamine 0.3 mg/kg in 100mL normal saline minibag administered over 15 min and placebo 10 mL normal saline syringe administered over 1 minute.; Other Names: Ketalar
Active Comparator: Ketamine IV push; Ketamine 0.3 mg/kg in a syringe pushed over 1 minutes. Placebo: 100 mL normal saline minibag infused over 15 minutes. Masking: placebo normal saline minibags and placebo syringes will appear identical to the normal saline minibus and syringes with ketamine.	Drug: Ketamine IV push; Ketamine 0.3 mg/kg in 10 mL normal saline syringe administered over 1 minute and placebo 100mL normal saline minibag administered over 15 min.; Other Names: Ketalar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side Effects	The difference in percentage of participants endorsing side effects between each arm of the study over 60 minutes.	0 - 60 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side Effects	The difference in percentage of participants endorsing side effects between each arm of the study at 5, 10, 15, 20, 30, 45, and 60 minutes.	5, 10, 15, 20, 30, 45, 60 minutes
Side Effect Severity	The difference in severity of side effects (0 - 4) experienced by participants in each arm of the study at 5, 10, 15, 20, 30, 45, and 60 minutes. 0 indicates no side effects and 4 most severe side effects.	5, 10, 15, 20, 30, 45, 60 minutes
How Bothersome Are the Side Effects?	The difference in how bothersome (0, not bothersome, to 4, very bothersome, on the Side Effect Rating Scale for Dissociative Anesthetics "SERSDA") the side effects experienced by participants in each arm of the study are at 5, 10, 15, 20, 30, 45, and 60 minutes. "0" (no side effects), "1" (weak), "2" (moderate), "3" ("bothersome") to "4" (very bothersome)	5, 10, 15, 20, 30, 45, 60 minutes
Reduction in Pain on Numeric Rating Scale.	The difference in pain numeric rating score (NRS 0-10) experienced by participants in each arm of the study at 5, 10, 15, 20, 30, 45, and 60 minutes. Pain numeric rating scale from 0 (no pain) to 10 (maximal pain).	5, 10 , 15, 20, 30, 45, 60 minutes

Collaborators and Investigators

• Sponsor: Alameda Health System

Publications and helpful links

General Publications

• Clattenburg EJ, Hailozian C, Haro D, Yoo T, Flores S, Louie D, Herring AA. Slow Infusion of Low-dose Ketamine Reduces Bothersome Side Effects Compared to Intravenous Push: A Double-blind, Double-dummy, Randomized Controlled Trial. Acad Emerg Med. 2018 Sep;25(9):1048-1052. doi: 10.1111/acem.13428. Epub 2018 May 25.

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: September 26, 2016
• First Submitted That Met QC Criteria: September 26, 2016
• First Posted (Estimate): September 28, 2016

Study Record Updates

• Last Update Posted (Actual): April 17, 2020
• Last Update Submitted That Met QC Criteria: April 4, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: ketamine; emergency department
• 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: 00002

Plan for Individual participant data (IPD)

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