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
|Condition or disease||Intervention/treatment||Phase|
|Burns||Drug: Ketamine Drug: Sodium chloride||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||46 participants|
|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|
|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|
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.
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
- 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.
- 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.
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
|Contact: Katharine Miles, MDfirstname.lastname@example.org|
|Contact: Jane Wido||708-216-5119|
|United States, Illinois|
|Loyola University Medical Center||Recruiting|
|Maywood, Illinois, United States, 60153|
|Contact: Katharine Miles, MD 708-216-4174 email@example.com|
|Contact: Jane Wido 708-216-5119 firstname.lastname@example.org|
|Principal Investigator:||Katharine Miles, MD||Loyola University|