Study	Treatment	Opioid consumption	Time to pain resolution (hours)	Length of hospitalization (days)	Tolerance to opioids
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	Ketamine: no data Placebo: no data
Bartolucci 2009	Ketoprofen (33 VOC episodes): Day 1 and 2: continuous IV infusion ketoprofen, 300 mg/day, 2 days Days 3–5: 100 mg oral ketoprofen, every 8 hr, 3 days Placebo (33 VOC episodes): Day 1 and 2: physiological saline continuous IV infusion, 2 days Days 3–5: oral placebo tablet, every 8 hr, 3 days	Median, mg Ketoprofen: 110 (IQR 46–195) Placebo: 88 (IQR 52.5–262.5)	Median, hours Ketoprofen: 51 (IQR 35.5–87) Placebo: 50 (IQR 36–103)	Ketoprofen: no data Placebo: no data	Ketoprofen: no data Placebo: no data
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 P > 0.05	Cetiedil 0.2 mg: no data Cetiedil 0.3 mg: no data Cetiedil 0.4 mg: no data Placebo: no data P > 0.05	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
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 (KTMF) (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	KTM: no data KTMF: no data	KTM: no data KTMF: no data	KTM: no data KTMF: no data	KTM: no data KTMF: no data
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	Morphine: no data butorphanol: no data	Butorphanol: no data Morphine: no data	Butorphanol: no data Morphine: no data	Butorphanol: no data Morphine: no data
Perlin 1994	Ketorolac (10 participants; 10 VOC episodes): bolus ketorolac 30 mg; 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	Meperidine mg mean total dose Ketorolac: 1866.7 (SD 1112.4) Placebo: 2804.5 (SD 795.1)	Ketorolac: no data Placebo: no data	Ketorolac: 3.3 Placebo: 7.2 P < 0.05	Ketorolac: no data Placebo: no data
		Mean daily dose Ketorolac: 523.6 (SD 222.1) Placebo: 662.4 (SD 68.6)
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	Morphine Tinzaparin: unclear Placebo: unclear	Mean hours Tinzaparin: 61.68 Placebo: 104.4	Mean days Tinzaparin: 7.08 Placebo: 12.06	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	Rescue morphine (0.1 mg/kg) at 30 min: Morphine: 27/54 Paracetamol: 24/52	Morphine: no data Paracetamol: no data	Morphine: no data Paracetamol: no data	Morphine: no data Paracetamol: no data
Wright 1992	Ketorolac (12 VOC episodes): IM ketorolac 60 mg, single dose Placebo (12 VOC episodes): IM saline, single dose	Mean (SD) meperidine mg Ketorolac: 231(92) Placebo: 250(85) P = 0.61	Ketorolac: no data Placebo: no data	Ketorolac: no data Placebo: no data	Ketorolac: no data Placebo: no data
CPS: categorical pain scale; hr: hour; IM: intramuscular; IQR: interquartile range; IV: intravenous; KTM: ketorolac + tramadol + metoclopramide; KTMF: ketorolac + tramadol + metoclopramide + fentanyl;min: minutes; SD: standard deviation; VAS: visual analogue scale; VCS: visual categorical score; VOC: vaso‐occlusive crisis; VRS: verbal rating scale.