Study	Treatment	Participant‐reported pain relief of 50% or greater	Participant‐reported pain relief of 30% or greater	Patient Global Impression of Change: both 'much improved' & 'much or very much improved'	Additional pain data reported by study
Arambasik 2013	Treatment group (17 participants; 17 VOC episodes): IV hydromorphone 2 mg 15 min later: IV hydromorphone 2 mg + IV ketamine 6.2 mg/kg Control group (20 participants; 20 VOC episodes): IV hydromorphone 2 mg 15 min later: IV hydromorphone 2 mg + IV saline placebo	Ketamine: no data Placebo: no data	Ketamine: no data Placebo: no data	Ketamine: no data Placebo: no data	VAS (1–10); mean (% decrease from arrival) At arrival Ketamine: 8.7 (95% CI 8.07 to 9.29) Placebo: 8.5 (95% CI 7.90 to 9.05)
					At administration Ketamine: 6.0 (95% CI 4.71, to 7.29); 31% Placebo: 7.0 (95% CI 6.20 to 7.85); 17.6%
					At disposition Ketamine: 5.2 (95% CI 4.01 to 6.46); 40.2% Placebo: 5.6 (95% CI 4.27 to 6.93); 34.1%
Bartolucci 2009	Ketoprofen (33 VOC episodes): Days 1 and 2: continuous IV ketoprofen infusion, 300 mg/day, 2 days Days 3–5: oral ketoprofen 100 mg, every 8 hr, 3 days Placebo (33 VOC episodes): Days 1 and 2: physiological saline continuous IV infusion, 2 days. Days 3–5: oral placebo tablet, every 8 hr, 3 days	Ketoprofen: no data Placebo: no data	Ketoprofen: no data Placebo: no data	Ketoprofen: no data Placebo: no data	CPS (0–3) daily mean scores; median Ketoprofen: 0.4 (IQR 0.2–0.7) Placebo: 0.4 (IQR 0.2–0.7)
					VAS (0–100) daily mean scores;median Ketoprofen: 12.6 (IQR 4.8–23.2) Placebo: 9.6 (IQR 5.8–33.2)
Benjamin 1986	Cetiedil 0.2 (16 participants; 16 VOC episodes): 0.2 mg/kg IV infusion, every 8 hr, 4 days, total 12 doses Cetiedil 0.3 (18 participants; 18 VOC episodes): 0.3 mg/kg IV infusion, every 8 hr, 4 days, total 12 doses Cetiedil 0.4 (13 participants; 13 VOC episodes): 0.4 mg/kg IV infusion, every 8 hr, 4 days, total 12 doses Placebo (16 participants; 16 VOC episodes): saline IV infusion, every 8 hr, 4 days, total 12 doses	Cetiedil 0.2 mg: no data Cetiedil 0.3 mg: no data Cetiedil 0.4 mg: no data Placebo: no data	Cetiedil 0.2 mg: no data Cetiedil 0.3 mg: no data Cetiedil 0.4 mg: no data Placebo: no data	Overall evaluation of treatment (good) Cetiedil 0.2 mg: 5/16 Cetiedil 0.3 mg: 4/18 Cetiedil 0.4 mg: 4/13 Placebo: 2/16	Cetiedil 0.2 mg: no data Cetiedil 0.3 mg: no data Cetiedil 0.4 mg: no data Placebo: no data
				Overall evaluation of treatment (good + excellent) Cetiedil 0.2 mg: 9/16 Cetiedil 0.3 mg: 10/18 Cetiedil 0.4 mg: 11/13 Placebo: 4/16
De Franceschi 2016	Treatment group VOC1 (KTM) (10 participants; 20 VOC episodes): continuous IV infusion ketorolac 0.86 mg/kg/day + tramadol 7.2 mg/kg/day + metoclopramide 0.57 mg/kg/day, for maximum of 72 hr Treatment group VOC2 (KT MF) (10 participants; 20 VOC episodes): continuous IV infusion ketorolac 0.86 mg/kg/day + tramadol 7.2 mg/kg/day + metoclopramide 0.57 mg/kg/day + fentanyl buccal single tablet 100 μg after 3 hr from beginning of multimodal analgesia, for maximum of 72 hr	At 6 hr KTM: 0/20 KTMF: 12/20	At 6 hr KTM: 1/20 KTMF: 20/20	KTM: no data KTMF: no data	KTM: no data KTMF: no data
		At 12 hr KTM: 4/20 KTMF: 18/20	At 12 hr KTM: 4/20 KTMF: 20/20
Gonzalez 1988	Butorphanol (9 participants; 12 VOC episodes): IM butorphanol 2 mg, repeated within 30–60 min until pain relief obtained, repeat every 2–4 hr, until discharge. Morphine (9 participants; 12 VOC episodes): IM morphine 6 mg, repeat within 30–60 min until pain relief obtained, repeated every 2–4 hr, until discharge	Butorphanol: no data Morphine: no data	Butorphanol: no data Morphine: no data	Good Butorphanol: 47.6% Morphine: 38.1%	VAS (0–100 mm); adjusted means overall Butorphanol: 44.42 Morphine: 46.08
				Excellent Butorphanol: 19.1% Morphine: 33.3%	Pain relief (0–100 mm); adjusted means overall Butorphanol: 43.79 Morphine: 55.50
Perlin 1994	Ketorolac (10 participants; 10 VOC episodes): ketorolac 30 mg bolus; continuous IV infusion ketorolac 120 mg, 5 mg/hr, total dose 150 mg (on first day), maximum 120 mg/day, up to 5 days Placebo (11 participants; 11 VOC episodes): bolus saline; continuous IV infusion saline, up to 5 days	Ketorolac: no data Placebo: no data	Ketorolac: no data Placebo: no data	Better Ketorolac: 3/10 Placebo: 4/11	VAS (0–100 mm); mean At baseline Ketorolac: 77.7 (95% CI 69.1 to 86.2) Placebo: 79.1 (95% CI 72.1 to 86.0) At 24 hr Ketorolac: 58.6 (95% CI 48.6 to 68.5) Placebo: 72.6 (95% CI 62.4 to 82.8) P < 0.05
				Much better Ketorolac: 3/10 Placebo: 0/11	VCS (0–3); mean At baseline Ketorolac: 2.5 Placebo: 2.6 At 24 hr Ketorolac: 2.0 Placebo: 2.4
				Better + much better Ketorolac: 6/10 Placebo: 4/11	VRS (0–4) at 24 hr; mean Ketorolac: 1.8 Placebo: 1.9
Qari 2007	Tinzaparin (127 participants; 127 VOC episodes): subcutaneous tinzaparin 175 IU/kg, once daily, 7 days Placebo (126 participants; 126 VOC episodes): subcutaneous placebo, once daily, 7 days	Tinzaparin: no data Placebo: no data	Tinzaparin: no data Placebo: no data	Tinzaparin: no data Placebo: no data	Tinzaparin: no data Placebo: no data
Rehmani 2013	Morphine (54 participants; 54 VOC episodes): IV morphine 0.1 mg/kg, single dose Paracetamol (52 participants; 52 VOC episodes): IV paracetamol 1 g, single dose	Morphine: no data Paracetamol: no data	Morphine: no data Paracetamol: no data	Morphine: no data Paracetamol: no data	VAS (0–100 mm) at 30 min; mean Morphine: 44 (95% CI 33 to 56) Paracetamol: 41 (95% CI 32 to 49) P = 0.72
Wright 1992	Ketorolac (12 VOC episodes): IM ketorolac 60 mg, single dose Placebo (12 VOC episodes): IM saline, single dose	Ketorolac: no data Placebo: no data	Ketorolac: no data Placebo: no data	Ketorolac: no data Placebo: no data	VAS (0–100 mm) at baseline; mean Ketorolac: 70.3 Placebo: 79.3 P = 0.26
					VAS (0–100 mm) at 4 hr; mean Ketorolac: 44 (SD 34) Placebo: 37 (SD 31) P = 0.49
CI: confidence interval; CPS: categorical pain scale; hr: hour; IM: intramuscular; IQR: interquartile range; IV: intravenous; KTM: ketorolac + tramadol + metoclopramide; KTMF: ketorolac + tramadol + metoclopramide + fentanyl;min: minute; SD: standard deviation; VAS: visual analogue scale; VCS: visual categorical score; VOC: vaso‐occlusive crisis; VRS: verbal rating scale.