Nebulized Ketamine to Nebulized Fentanyl for Treating Acute Painful Conditions in the ED

This is a prospective, randomized, double-blind trial comparing the analgesic efficacy and safety of nebulized ketamine administered at 0.75 mg/kg via BAN to nebulized fentanyl administered at 3 mcg/kg via BAN to adult patients presenting to the ED of Maimonides Medical Center with acute painful conditions of moderate to severe intensity. The dosing of nebulized fentanyl at three mcg/kg is based on two randomized, dose-finding clinical trials of acute pain where a one mcg/kg dose was compared to a 3 mcg/kg dose with resultant analgesic superiority of the 3 mcg/kg dose (26, 27). The dose of nebulized ketamine is based on the results of our own randomized clinical trial, which showed that 0.75 mg/kg of nebulized ketamine was as effective at relieving short-term pain in the ED as 1 mg/kg and 1.5 mg/kg. Upon meeting the eligibility criteria, patients will be randomized into two study groups: Nebulized KetaBAN (Ketamine via BAN) and Nebulized FentaBAN (Fentanyl via BAN).

The on-duty ED pharmacist will prepare either a breath-actuated nebulizer (BAN) with 0.75 mg/kg of ketamine or a BAN with 3 mcg/kg of fentanyl, depending on the randomization list, which will be made in SPSS (version 24; IBM Corp., Armonk, NY) with a block randomization of every 10 participants. The medication will be delivered to the treating nurse in a blinded fashion. The nebulization of study drugs via BAN will have a minimum time of 5 minutes and a maximum time of 15 minutes. If a patient requires further analgesia, a second dose of either Ketaban or Fentaban will be offered, or intravenous (IV) fentanyl at 0.75 mcg/kg will be administered as a rescue analgesia.

In addition, study investigators will measure the residual volume of ketamine and fentanyl remaining in the breath-actuated nebulizer after each treatment and document the results on a waste sheet designed by the pharmacy staff. The pharmacist will receive this sheet and use it to determine the actual dose that each study participant received based on their initial randomization group. According to the departmental policy on the waste of controlled substances, a treating nurse will discard the remaining ketamine and fentanyl in the breath-actuated nebulizer.

A study investigator will approach each patient for written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization after the treating emergency medicine physician has evaluated them and they meet the study eligibility requirements. When English will not be the participant's primary language, a language-appropriate consent form will be used, and non-investigator, hospital-employed, trained interpreters, or licensed telephone interpreters will assist in the acquisition of informed consent. Baseline pain score will be determined with an 11-point numeric rating scale (0 to 10), described to the patient as "no pain" being 0 and "the worst pain imaginable" being 10. A study investigator will record the patient's body weight and baseline vital signs.

Study investigators will record pain scores, vital signs, and adverse effects at 15, 30, 60, 90, and 120 minutes. If patients report a pain numeric rating scale score of 5 or greater at any of the aforementioned time points and request additional pain relief, intravenous (IV) fentanyl at 0.75 mcg/kg will be administered as a rescue analgesic.

The ED pharmacist, research manager, and statistician will be the only ones with knowledge of the study arm to which each participant will be randomized. The treating providers, participants, and the data collection research team will be blind to the medication received.

All data will be recorded on data collection sheets, including patients' sex, demographics, medical history, vital signs, adverse events, and need for rescue medication, etc., and entered into SPSS (version 24.0; IBM Corp.) by the research manager. The research manager and statistician (Michael Silver) will work independently of any data collection to develop the randomization list, confirm the acquisition of written consent for all participants, and conduct statistical analyses. The randomization will be Bock Randomization every 10 subjects.