40 Analgesia in Sickle Cell Disease: Do We Give the Right Dose? A Systematic Review of Pharmacokinetic Studies

Abstract Background Children with sickle cell disease (SCD) suffer from lifelong episodes of unpredictable acute pain that alter their quality of life. Despite prompt pain treatment, hospitalization is often required for pain management. SCD is a multisystemic disease affecting organ function (e.g., renal hyperfiltration, change in liver blood flow). Altogether, these changes could alter pharmacokinetics (PK). Objectives We hypothesize that SCD leads to changes in PK of analgesics potentially contributing to treatment failure using regular medication doses. Design/Methods A systematic literature review to describe the current evidence on the effect of SCD on analgesic disposition in children was performed by a librarian on 5 databases from inception until February 2021 and independently assessed by two reviewers. All full text articles, including PK data in children with SCD, were included. The reported differences in PK parameters between children with and without SCD were examined. Results Among 5170 retrieved abstracts, 84 full text articles were reviewed, and 7 studies were included on 128 patients. Studied drugs were morphine (IV and PO), lidocaine (IV), methadone (IV) and rofecoxib (PO). In children with SCD, clearance of IV morphine was 42-61% higher compared with non-SCD controls. Hepatic metabolism of lidocaine was decreased in children with SCD compared to healthy controls. No significant PK changes were noted for methadone and rofecoxib compared with non-SCD controls. Conclusion SCD leads to significant changes in PK of analgesics, but data are scarce. Increased clearance of morphine suggests that higher doses may be needed in children with SCD. Data on commonly used analgesics like acetaminophen, ibuprofen and ketamine are critically missing. Dosing of analgesics adapted to SCD are needed and may potentially improve pain control in this population.