Randomized clinical trial of nebulized fentanyl citrate versus i.v. fentanyl citrate in children presenting to the emergency department with acute pain

Abstract

Objectives: To compare the pain relief achieved with nebulized fentanyl citrate with intravenous (i.v.) fentanyl citrate in children presenting to the emergency department (ED) with painful conditions to determine if nebulized fentanyl is a feasible alternative to i.v. fentanyl for the treatment of acute pain in children.

Methods: This was a randomized controlled trial in an urban county medical center ED with an annual census of 99,000 visits. ED patients, aged 6 months to 17 years, presenting with acute pain who were going to be treated with i.v. pain medications, were eligible for enrollment. After the parents had provided informed consent, and children older than 6 years had provided assent, patients were randomized (1:2) to receive either fentanyl citrate i.v. (1.5 microg/kg) or fentanyl citrate by breath-actuated nebulizer (3.0 microg/kg). Patients aged 6 years and older completed a 100-mm visual analog scale (VAS) describing their pain, and patients younger than 6 years had their pain assessed by the treating physician using the Children's Hospital of Eastern Ontario Pain Scale. Additionally, treating physicians used a 100-mm VAS to describe their perception of the patients' pain. These pain measurements were taken before treatment and every 10 minutes thereafter for 30 minutes. Baseline blood pressure, heart rate, and oxygen saturation were also measured before treatment and every 10 minutes for 30 minutes. After 30 minutes, physicians were asked whether or not they believed the medication provided adequate pain relief for the patient. Parents were asked to rate their satisfaction with the treatment using a five-point scale. Patients who received additional pain medications by any method before the 30-minute measurement period was completed were considered treatment failures. Data were compared using descriptive statistics and 95% confidence intervals; the rates of adequate pain relief between the groups were compared using Fisher exact tests.

Results: Forty-one patients were enrolled in the study; 14 were randomized to i.v. fentanyl (ten actually received it), and 27 patients were randomized to nebulized fentanyl (31 actually received it). In the four patients who were randomized to i.v. fentanyl but received nebulized fentanyl, the parents requested the nebulized medication after being told their child had been randomized to i.v. fentanyl. Baseline pain VAS scores were 82.8 mm (SD +/-14.3, 69-100) in the i.v. group and 76.2 mm (SD +/-20.5, 34-100) in the nebulized group. There were five treatment failures: one who received i.v. fentanyl and four who received nebulized fentanyl. The four patients who were considered treatment failures in the nebulized fentanyl group were all younger than 3 years and had difficulty triggering the breath-actuated nebulizer. The mean decrease in pain for patients remaining in the study was 55.1 mm (95% CI = 40.3 to 70.0) for the i.v. group and 77.8 mm (95% CI = 67.4 to 88.4) for the nebulized group. The pain treatment was described as adequate by the treating physician in eight of 14 patients in the i.v. group and 20 of 27 patients in the nebulized group (p = 0.42). No adverse events were detected.

Conclusions: Nebulized fentanyl citrate 3 microg/kg through a breath-actuated nebulizer appears to be a feasible alternative to i.v. fentanyl citrate for a variety of painful conditions in patients older than 3 years.