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

NCT ID: NCT03049930

Last Updated: 2019-03-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-27
• Study Completion Date: 2020-08-31

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.

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.

Conditions

Burns

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

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.

Placebo

Participants randomized to this arm will receive 0.9 mg/ml sodium chloride, infused at a rate of 0.2 ml/kg/hour

Group Type: PLACEBO_COMPARATOR

Sodium chloride

Intervention Type: DRUG

Participants randomized to the placebo arm will receive 0.9 mg/ml sodium chloride, infused at a rate of 0.2 ml/kg/hour

Interventions

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.

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Ketalar; Placebo

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Loyola University

OTHER

Sponsor Role: lead

Responsible Party

Katharine Miles

Assistant Professor of Anesthesiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Katharine Miles, MD

Role: PRINCIPAL_INVESTIGATOR

Loyola University

Locations

Loyola University Medical Center

Maywood, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Katharine Miles, MD

Role: CONTACT

katharine.miles@lumc.edu

708-216-4174

Jane Wido

Role: CONTACT

708-216-5119

Facility Contacts

Katharine Miles, MD

Role: primary

katharine.miles@lumc.edu

708-216-4174

Jane Wido

Role: backup

jwido@lumc.edu

708-216-5119

References

Ahern TL, Herring AA, Miller S, Frazee BW. Low-Dose Ketamine Infusion for Emergency Department Patients with Severe Pain. Pain Med. 2015 Jul;16(7):1402-9. doi: 10.1111/pme.12705. Epub 2015 Feb 3.

Reference Type: BACKGROUND

PMID: 25643741 (View on PubMed)

Gupta A, Devi LA, Gomes I. Potentiation of mu-opioid receptor-mediated signaling by ketamine. J Neurochem. 2011 Oct;119(2):294-302. doi: 10.1111/j.1471-4159.2011.07361.x. Epub 2011 Sep 20.

Reference Type: BACKGROUND

PMID: 21692801 (View on PubMed)

Kaur S, Saroa R, Aggarwal S. Effect of intraoperative infusion of low-dose ketamine on management of postoperative analgesia. J Nat Sci Biol Med. 2015 Jul-Dec;6(2):378-82. doi: 10.4103/0976-9668.160012.

Reference Type: BACKGROUND

PMID: 26283834 (View on PubMed)

Mion G, Villevieille T. Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings). CNS Neurosci Ther. 2013 Jun;19(6):370-80. doi: 10.1111/cns.12099. Epub 2013 Apr 10.

Reference Type: BACKGROUND

PMID: 23575437 (View on PubMed)

Other Identifiers

209459

Identifier Type: -

Identifier Source: org_study_id