Introduction:
Bromelain enzymatic debridement of burn wounds has been shown to be an effective tool for selectively removing eschar early and decreasing the frequency and size of skin grafts. One of the major downsides to the product is that it is very painful. Many centers use continuous infusions of narcotics, ketamine, and sedatives- requiring a higher level of care (e.g. ICU or stepdown). Ketamine is a wellknown dissociative, sedative-hypnotic medication that has been utilized for reduction in pain, as a procedural sedation method, and its usage results in reduction of post-traumatic stress disorder. However, intravenous (IV) ketamine often requires ICU level of care and is considered moderate or deep sedation, especially when given with other medications. Oral ketamine offers advantages in certain situations and decreases the need for higher level of care and preprocedural fasting. The purpose of this study is to evaluate whether oral ketamine can be utilized as an alternative to continuous infusions of IV medications for bromelain treatment.

Methods:
A retrospective chart review was conducted on a series of patients over a six-month period that received oral ketamine (for analgesia) and oral lorazepam (for anxiolysis and prevention of dysphoria) while undergoing bromelain-based selective enzymatic debridement application at an academic burn center. Data extracted included patient demographics, burn characteristics, baseline opioid medication regimen, pre procedural sedative and analgesic agents with corresponding administration information, enzyme application information, sedatives and analgesics used for the procedure, peri-procedure pain scores, any adjunct medications required, and vital signs. Presence of undesirable events such as respiratory insufficiency (desaturations <93%, need for bag-valve mask, or intubation), hypertensive urgency (SBP>180, DBP>110 without signs of end organ dysfunction), dysphoric reactions, and uncontrolled pain were also reported. Oral ketamine (2-4 mg/kg) was administered approximately 30 minutes prior to the pre-determined procedure application time. Patients were monitored to be in compliance with sedation guidelines, including continuous capnography along with supplemental oxygen. Patients were given small IV bolus doses of narcotics as needed during the procedure, in addition to their baseline oral multimodals and narcotics. The measurement of pain intensity was the 1-10 verbal rating scale. Minimal pain was defined as the mean numerical pain score being <4 or the patient clinically observed as sleeping with normal vitals when nurses went in to assess pain. Significant pain during treatment was defined as a score of ≥7 and a deviation of more than 2 points from pre-procedure baseline. Patients were not made NPO for the procedure.

Results:
Ten patients were included in the study. Four patients (40%) had minimal pain during the enzymatic debridement process, 3 (30%) patients were clinically observed as intermittently sleeping through most of their procedure, 3 (30%) patients reported 10/10 pain at some point during treatment 2 had 10/10 pain before treatment) and three (30%) reported significant treatment pain. Five patients were treated on the floor, while 7 were treated in the ICU. The median ketamine dose was 225 mg (IQR:177,250), or 3mg/kg (IQR:2.75,3). Additional oral and IV opioids received during the 8–14-hour interval was 21 morphine milligram equivalents. The median benzodiazepine dosing before and during enzymatic debridement was 1.4 lorazepam milligram equivalents. All patients were noted to have received scheduled dose acetaminophen, gabapentin, and oxycodone in the morning before enzyme application, while 60% received methocarbamol. Three patients (30%) developed hypertensive urgency, 2 (20%) of whom reported 10/10 pain, and all 3 received 10mg IV labetalol. None of the patients experienced dysphoric reactions or respiratory insufficiency.

Conclusions:
This preliminary study reveals oral ketamine administration is safe and effective for pain control during bromelain-based selective enzymatic debridement. Most patients in the study did not require large doses adjuvant IV opioids, had acceptable pain control, and there were no significant adverse effects. Future large, prospective studies should evaluate dosing and timing for optimal patient outcomes.