Adjuvant interventions with opioids for vaso-occlusive crisis in sickle cell disease: A mixed treatment network meta-analysis of randomized controlled clinical trials.

OBJECTIVE

Vaso-occlusive crisis is the most common clinical feature requiring opioid analgesics in patients with sickle cell disease. We conducted a network meta-analysis to compare the drugs that can be used as add-on with opioids for vaso-occlusive crisis.

DESIGN

Network meta-analysis of randomized clinical trials.

PATIENTS: Sickle cell disease patients with vaso-occlusive crisis receiving adjuvants to opioids for pain management.

MAIN OUTCOME MEASURES: A number of patients with complete pain relief and pain scores assessed either by visual ana-log or by a numerical rating scale were the primary outcomes. Adverse events and dose of opioids (in morphine equiva-lents) for pain alleviation between the treatment arms were the secondary outcome measures.

RESULTS

Eleven studies evaluating the addition of ketorolac, magnesium sulfate, ketoprofen, ibuprofen, methadone, inhalational nitric oxide, methylprednisolone, and arginine with morphine were obtained. The pooled analysis showed a favorable effect in the pain reduction for the additions of arginine {-2 [-3.39, -0.61]} and ibuprofen {-1.7 [-3.26, -0.14]} with morphine. Arginine has high probability of being the "best" in the pool followed by ibuprofen. No significant differ-ences were observed in the risk of adverse events {ketoprofen-0.84 [0.42, 1.65]; magnesium sulfate-1.81 [0.64, 5.81]; and arginine-2.08 [0.18, 24.31]}. A significant lower dose of opioid was required when given adjunctive to argin-ine, inhalational nitric oxide, and methylprednisolone.

CONCLUSION

We observed that arginine and ibuprofen could produce additional analgesic effects when combined with morphine in vaso-occlusive crisis.