Ketamine Plus Haloperidol: An Effective Opioid Alternative in the ED

Researchers analyzed the analgesic effect of using ketamine in combination with haloperidol compared with fentanyl.

Ketamine with haloperidol may be more effective at controlling acute pain than fentanyl among patients presenting to the emergency department (ED), according to study findings published in the American Journal of Emergency Medicine.

Researchers conducted a noninferiority, double-blind, randomized clinical trial at the Tehran University of Medical Sciences in Iran. Patients (N=200) who presented to the ED with acute pain (Numerical Rating Scale [NRS] score >5) were randomly assigned to receive 2.5 mg haloperidol with 0.3 mg/kg ketamine (n=100) or 1 μg/kg fentanyl (n=100). Patients were assessed for pain at 5, 10, 15, and 30 minutes after injection, the need for rescue medication, and for adverse effects.

The ketamine and fentanyl cohorts had a mean age of 39.65±13.07 and 40.86±15.59 years; 68% and 71% were men; and mean pain scores were 8.79±1.372 and 8.46±1.382 points, respectively. The most common pain indications were orthopedic trauma, renal colic, abdominal pain, and low back pain, among others.

At 5 minutes, the average pain score was 2.34±3.03 points among ketamine recipients compared with 5.55±2.44 among fentanyl recipients (P<.001). Ketamine recipients compared with fentanyl recipients continued to report lower pain scores through 30 minutes (mean, 1.60±2.49 vs 3.57±2.52 points; P<.001).

Significantly more patients who received ketamine compared with patients who received fentanyl reported no pain at 5 (54% vs 6%; P<.001) and 10 (67% vs 11%; P<.001) minutes.

Compared with baseline, the ketamine recipients had increased agitation scores at 5 and 10 minutes, but these scores decreased at 15 and 30 minutes (P=.033).

Rescue analgesia was required by 9% of the ketamine and 24% of the fentanyl cohorts (P=.04).

The proportion of patients reporting satisfaction after receiving ketamine and fentanyl were (75% vs 28%) at 5, (85% vs 49%) 10, (89% vs 63%) 15, and (85% vs 67%) at 30 minutes, respectively.

Among the ketamine cohort, 5 patients experienced vomiting and 4 had emergence phenomenon. For the fentanyl group, 2 patients had apnea. In addition, fentanyl was associated with decreased heart rate, respiration rate, and arterial pressure.

The study authors reported difficulty in obtaining informed consent prior to randomization due to patient pain levels.

“Due to the absence of fatal complications such as respiratory failure and the lack of need for monitoring, injection of ketamine with haloperidol can be used as one of the safest and most appropriate sedatives in the ED,” the study authors noted.


Moradi MM, Moradi MM, Safaie A, Baratloo A, Payandemehr P. Sub dissociative dose of ketamine with haloperidol versus fentanyl on pain reduction in patients with acute pain in the emergency department; a randomized clinical trial. Am J Emerg Med. Published online February 6, 2022. doi:10.1016/j.ajem.2022.02.012