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Intraoperative Low-dose Ketamine Infusion as the Main Analgesic in Burn Patients

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ClinicalTrials.gov Identifier: NCT03049930
Recruitment Status : Recruiting
First Posted : February 10, 2017
Last Update Posted : March 14, 2019
Sponsor:
Information provided by (Responsible Party):
Katharine Miles, Loyola University

Brief Summary:
The purpose of this study is to determine whether a low-dose ketamine infusion can be used as the main intra-operative analgesic in different burn patients, and thereby reduce the total intra-operative opioid requirement. Secondary objectives are to determine whether this low-dose ketamine infusion will lengthen the amount of time to the first narcotic given in the recovery room or ICU, and whether pain scores for awake patients will be lower post-operatively.

Condition or disease Intervention/treatment Phase
Burns Drug: Ketamine Drug: Sodium chloride Phase 4

Detailed Description:

Burn patients suffer from several types of pain (due to stimulation of mechanoreceptors, nociceptors, and chemical stimulation) as well as other injuries. Multiple agents are used to control pain in this special group. Due to different pain mechanisms and the up-regulation of the mu receptors, numerous pain controlling modalities should be sought. Opioids are the mainstay in treating pain in such patients. Adjuvant non-opioid agents are less effective if used alone. These agents include non-steroidal, anti-inflammatory drugs (NSAIDs), α-2 antagonists, local anesthetics and ketamine. Regional blocks can be used in the perioperative period if there are no contraindications, but catheters cannot be left in place for an extended period of time. Opioids have many side effects such as respiratory depression, nausea, vomiting, itching, urinary retention, and hyperalgesia. The latter is of concern in any patient on chronic opioids, including burn patients.

Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) antagonist that has been successfully used in burn intensive care units (BICUs) to provide pain for dressing changes. It also has been in use in BICUs to supplement the analgesic effect of opioids. Ketamine exerts its clinical analgesic effect mainly by NMDA antagonism, but it also interacts with other receptors such as AMPA monoaminergic, nicotinic, muscarinic, and mu, delta, and kappa opioid receptors. It resembles local anesthetics in its interaction with sodium channels. Low dose ketamine infusion (LDKI) has been used as a postoperative analgesic in different patients group for various duration of time. Some studies have shown some benefit to using intraoperative low-dose ketamine in non-burn surgery in order to reduce post-operative opiate requirement. Little is known, from the literature, if an intraoperative low-dose ketamine infusion can be used as the main analgesic in burn patients in general, and in severely burned patients in specific.

Previous studies have shown that ketamine potentiates the analgesic effects of low-dose fentanyl and, to a lesser degree, low-dose morphine by stimulation of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2). It also increases the duration of opioid-induced analgesia, delays opioid induced tolerance, and plays a role in preventing opioid-induced hyperalgesia by delaying desensitization and by improving resensitization of ERK 1/2 signaling. From this pharmacologic standpoint, it is advantageous over other pain modalities in hemodynamically-compromised burn patients.

Ketamine is being used extensively in burn ICUs but the low-dose infusion of ketamine did not capture as much attention in treating burn patients in the operating room (OR). Burn patients come to the OR numerous times for wound debridement, skin grafting or unrelated surgeries. The use of inhalation anesthetics poses the risk of hypotension in these hemodynamically fragile patients. Opioids are still the main agents in treating such patients in the OR and they are sometimes given in very high doses, due to the resistance and up-regulation of the mu opioid receptors mentioned above. These doses are often not very effective in controlling pain and can lead to hypotension if combined with potent inhalation agents.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The intervention study model is a randomized block design using a 1:1 allocation scheme
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: No other parties are masked in the clinical trial
Primary Purpose: Treatment
Official Title: Intraoperative Low-dose Ketamine Infusion as the Main Analgesic in Burn Patients
Actual Study Start Date : February 27, 2018
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Burns

Arm Intervention/treatment
Experimental: Ketamine
Participants randomized to this arm will receive ketamine (1 mg/ml solution) infused at 0.2 mg/kg/hour (0.2 ml/kg/h) for a maximum of 20 ml/hour.
Drug: Ketamine
Ketamine is a medication used for starting and maintaining anesthesia. Participants randomized to the ketamine arm will receive 1 mg/ml solution infused at 0.2 mg/kg/hour (0.2 ml/kg/h) for a maximum of 20 ml/hour.
Other Name: Ketalar

Placebo Comparator: Placebo
Participants randomized to this arm will receive 0.9 mg/ml sodium chloride, infused at a rate of 0.2 ml/kg/hour
Drug: Sodium chloride
Participants randomized to the placebo arm will receive 0.9 mg/ml sodium chloride, infused at a rate of 0.2 ml/kg/hour
Other Name: Placebo




Primary Outcome Measures :
  1. Intraoperative fentanyl [ Time Frame: 24 hours ]
    For all participants, the dose of intraoperative fentanyl will be recorded in micrograms and compared between the two arms.


Secondary Outcome Measures :
  1. Time to the first narcotic [ Time Frame: 24 hours ]
    For all participants, the hours to the first dose of post-operative narcotic will be recorded and compared between the two arms.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All adult burn patients aged 18-80 presenting to the operating room, both intubated and non-intubated
  • Patients having a procedure performed in Russo operating rooms at Loyola University Medical Center

Exclusion Criteria:

  • Allergy to ketamine or benzodiazepines
  • Ketamine use in the preceding 24 hours
  • Children (patients under age 18), prisoners, pregnant or breastfeeding women, patients with psychosis, patients with developmental delay, and any condition which, in the opinion of the investigator, would prevent full participation in this study or would interfere with the evaluation of the trial endpoints.
  • Increased intracranial pressure at the discretion of the investigator
  • Increased intraocular pressure at the discretion of the investigator
  • Porphyria at the discretion of the investigator
  • Thyroid disorders at the discretion of the investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03049930


Contacts
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Contact: Katharine Miles, MD 708-216-4174 katharine.miles@lumc.edu
Contact: Jane Wido 708-216-5119

Locations
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United States, Illinois
Loyola University Medical Center Recruiting
Maywood, Illinois, United States, 60153
Contact: Katharine Miles, MD    708-216-4174    katharine.miles@lumc.edu   
Contact: Jane Wido    708-216-5119    jwido@lumc.edu   
Sponsors and Collaborators
Loyola University
Investigators
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Principal Investigator: Katharine Miles, MD Loyola University

Publications:
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Responsible Party: Katharine Miles, Assistant Professor of Anesthesiology, Loyola University
ClinicalTrials.gov Identifier: NCT03049930     History of Changes
Other Study ID Numbers: 209459
First Posted: February 10, 2017    Key Record Dates
Last Update Posted: March 14, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share individual participant data

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Katharine Miles, Loyola University:
Burns
Ketamine
Anesthesia
Additional relevant MeSH terms:
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Ketamine
Burns
Wounds and Injuries
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action