Ketamine Use in Hospitalized Children and Young Adults with Sickle Cell Disease

Background National societies including the American Society of Hematology recommend ketamine, an N-Methyl-D-Aspartate receptor antagonist, as an opioid sparing adjunct for the treatment of refractory pain in sickle cell disease (SCD). Little is known regarding how it is being used nationally to treat hospitalized individuals with SCD. Aims: To describe ketamine use over time and examine associations between ketamine use and healthcare utilization outcomes in patients with SCD admitted to children's hospitals. Methods: We performed a multi-center cross-sectional study of individuals ≥ 6 months with SCD admitted to a Pediatric Health Information System (PHIS) contributing children's hospital (n= 43) from 2016-2022. We used ICD-10 diagnosis codes to identify SCD hospitalizations, excluding those with OR charges, direct admits, or transfers. Our outcome of interest was ketamine use during hospitalizations. To determine if ketamine use was associated with outcomes (i.e., length of stay (LOS), any cause 14-day readmission, parenteral opioid use during hospitalization), we used generalized estimating equations adjusting for patient demographics, hospital, hydroxyurea use and number of SCD related hospitalizations in the year prior as a proxy for SCD severity. We also tested whether early (≤ 72 hours) versus late (>72hours) ketamine use during admission was associated with hospital outcomes. Results: 15,261 children and young adults with SCD had a total of 64,545 hospitalizations. Ketamine was used in 2,809 (4.3%). Ketamine use increased from 2.3% of hospitalizations in 2016 to 5.9% in 2022 (p<.001). Factors most associated with ketamine use included older age and most recent years. 85% of all hospitalizations in which ketamine was used for pain were in children 12 years of age or older. An increasing percentage of hospitalizations with ketamine use was also observed (2016: 2.3%, 2017: 2.8%, 2018: 3.8%, 2019: 4.6%, 2020: 5.2, 2021: 5.9%, 2022: 5.9%). Ketamine was associated with longer LOS (7 days [IQR 4,10] vs. 3 [IQR 1,4], p <.001), readmission (21.4% vs 13.8%, p <.001), and parenteral opioid days (5 days [IQR 3,8] vs. 2 [IQR 0,3], p <.001), but also greater hydroxyurea use (64.5% vs 51%, p <.001) and number of hospitalizations in the year prior (4 days [IQR 1,8] vs. 2 [IQR 0,4], p <.001) compared to no ketamine. Early vs. late ketamine use was associated with shorter LOS (6 days [IQR 4,9] vs. 12 [IQR 9,16]) and less parental opioid days (4 days [IQR 2,7] vs. 9 [IQR 6,13]). Summary/Conclusion: While ketamine was used in less than 5% of hospitalized children and young adults with SCD from 2016-2022, its annual use has more than doubled over this time period. In those treated with ketamine, the association with decreased LOS and days on parenteral opioids with early compared to late ketamine use calls for randomized control studies to determine patients that would benefit most from ketamine use and if early initiation should be standard of care.