Randomized clinical trial comparing the safety and efficacy of a hydromorphone titration protocol to usual care in the management of adult emergency department patients with acute severe pain

Study objective: We test the efficacy and safety of the "1+1" (1 mg plus 1 mg 15 minutes later if needed) hydromorphone protocol against usual care of emergency department (ED) patients with acute severe pain. Methods: This was a prospective, randomized clinical trial of ED patients with acute severe pain. The 1+1 protocol specifies administration of 1 mg intravenous hydromorphone, followed by a second dose of 1 mg intravenous hydromorphone 15 minutes after the first bolus if the patient answers yes to the question, "Do you want more pain medication?" Usual care is the administration of any intravenous opioid, with type and dose chosen by the ED attending physician. Usual care patients who wanted more medication at 15 minutes were treated at the physician's discretion. At 60 minutes, all patients were asked again whether they wanted more pain medication. The primary outcome was successful treatment defined a priori as not wanting additional analgesia at either 15 or 60 minutes after the initial bolus. The primary endpoint was the difference in the proportion of patients with successful treatment who received the complete 1+1 protocol versus usual care with a per-protocol analysis. An intention-to-treat analysis was also performed. A 10% difference in rate of successful treatment was chosen a priori as a clinically meaningful difference. Results: Of 167 patients in the 1+1 group, 156 received the full 1+1 protocol, whereas 171 received usual care. Of patients who received the 1+1 protocol, 92.3% (144/156) had successful treatment versus 76.6% (131/171) of usual care patients (difference=15.7%; 95% confidence interval 7.9% to 23.3%). In the intention-to-treat analysis, 86.8% (145/167) of patients randomized to the 1+1 group received successful treatment versus 76.6% (131/171) of usual care patients (difference=10.2%; 95% confidence interval 2.0% to 18.3%). No patient required naloxone. One patient in the 1+1 group and 2 patients in the usual care group had transient oxygen saturation less than 95%. The incidence of all adverse effects was similar in both groups. Conclusion: When analyzed per protocol or with the more conservative intention-to-treat analysis, the 1+1 hydromorphone protocol is statistically and clinically more efficacious than usual care. Safety profiles were similar in both groups.