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

Authors

  • Kannan Sridharan, MD, DM
  • Gowri Sivaramakrishnan, MDS

DOI:

https://doi.org/10.5055/jom.2020.0580

Keywords:

pain crisis, sickle cell anemia, hemoglobinopathies

Abstract

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 analog or by a numerical rating scale were the primary outcomes. Adverse events and dose of opioids (in morphine equivalents) 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 differences 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 arginine, 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.

Author Biographies

Kannan Sridharan, MD, DM

Associate Professor, Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences, Manama, Bahrain

Gowri Sivaramakrishnan, MDS

Dental Specialist (Prosthodontist), Dental Training Department, Ministry of Health, Bahrain

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Published

07/01/2020

How to Cite

Sridharan, MD, DM, K., and G. Sivaramakrishnan, MDS. “Adjuvant Interventions With Opioids for Vaso-Occlusive Crisis in Sickle Cell Disease: A Mixed Treatment Network Meta-Analysis of Randomized Controlled Clinical Trials”. Journal of Opioid Management, vol. 16, no. 4, July 2020, pp. 267-75, doi:10.5055/jom.2020.0580.