Gonzalez 1988.

Methods	Allocation: randomized Controlled: active comparator Blinding: double‐blind Arm: 2‐arm, parallel treatment groups Centre: single centre Study duration: not reported
Participants	Inclusion criteria: adults aged 18–65 years with SCD treated in the emergency department Exclusion criteria: history of drug or alcohol abuse; opioid tolerance; hypersensitivity; allergy to morphine or butorphanol; pregnancy; breastfeeding; acute myocardial infarction within 6 months; daily use of narcotic analgesic during the last week Baseline characteristics N: 18 participants Gender: F 6, M 12 Age (mean): 29.3 (SD 7.7) years Number randomized: 9 butorphanol; 9 morphine Number completed: 9 butorphanol; 9 morphine Setting and location: primary emergency department, Medical College of Virginia Hospital, USA
Interventions	Duration of treatment: not explicitly stated Follow‐up period: not explicitly stated Treatment group (9 participants; 12 VOC episodes): IM butorphanol 2 mg, repeated within 30–60 minutes if needed until initial pain relief obtained. Dose repeated every 2–4 hr to maintain a pain relief rating of ≤ 50 mm until discharge Control group (9 participants; 12 VOC episodes): IM morphine 6 mg, repeated within 30–60 minutes if needed until initial pain relief obtained. Dose repeated every 2–4 hr to maintain a pain relief rating of ≤ 50 mm until discharge Standard treatments to all groups: dextrose 5% and 0.45% saline IV infusion 150 mL/hr Cointerventions: IM prochlorperazine 5–10 mg as needed for nausea or vomiting Cointerventions/additional analgesia: standard IV hydration
Outcomes	Primary outcomes Pain (LAS, VAS) Secondary outcomes Global assessment of treatment as decided by nurse Level of alertness Vital signs
Notes	Sources of funding: supported by a grant from Bristol‐Meyers United States Pharmaceutical Group, Evansville, IN, USA.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "patients were randomly assigned on each visit to receive either 2 mg IM butorphanol or 6 mg IM morphine."
Allocation concealment (selection bias)	Unclear risk	Comment: no technical details of allocation concealment.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "the patient and the medical and nursing staff were blinded to the identity of the assigned drug."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "the patient and the medical and nursing staff were blinded to the identity of the assigned drug" Comment: nursing staff made patient assessments, so likely to be adequate.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: all participants were accounted for from randomization, through treatment, to follow‐up. However, see 'Size' and 'Other Bias' domains below.
Selective reporting (reporting bias)	Low risk	Comment: no protocol available, but all planed outcomes were reported in results.
Size	High risk	Comment: total 18 participants (45 events), some randomized twice, < 50 participants per treatment arm.
Other bias	High risk	Comment: unit of analysis issue, 12 events per treatment arm. However, unit of randomization was the painful crisis (45 randomized crises events among 18 participants), random‐effects analysis took this unit of analysis issue appropriately into account.