Original Investigation
September 9, 2024
Lactated Ringer vs Normal Saline Solution During Sickle Cell Vaso-Occlusive Episodes
Augusta K. Alwang, Anica C. Law, Elizabeth S. Klings, et al
JAMA Intern Med. Published online September 9, 2024. doi:10.1001/jamainternmed.2024.4428
Question What is the comparative effectiveness of lactated Ringer solution vs normal saline for fluid resuscitation in inpatients with sickle cell disease and vaso-occlusive episodes?
Findings In this multicenter retrospective cohort study, use of lactated Ringer solution was associated with more hospital free-days, shorter hospital length of stay, and lower 30-day readmission risk compared with normal saline.
Meaning In a multicenter retrospective cohort study and target trial emulation, patients with sickle cell disease and vaso-occlusive episodes who received lactated Ringer solution had small but significant improvements in outcomes compared with patients who received normal saline.
Abstract
Importance Sickle cell disease (SCD), a clinically heterogenous genetic hemoglobinopathy, is characterized by painful vaso-occlusive episodes (VOEs) that can require hospitalization. Patients admitted with VOEs are often initially resuscitated with normal saline (NS) to improve concurrent hypovolemia, despite preclinical evidence that NS may promote erythrocyte sickling. The comparative effectiveness of alternative volume-expanding fluids (eg, lactated Ringer [LR]) for resuscitation during VOEs is unclear.
Objective To compare the effectiveness of LR to NS fluid resuscitation in patients with SCD and VOEs.
Design, Setting, and Participants This multicenter cohort study and target trial emulation included inpatient adults with SCD VOEs who received either LR or NS on hospital day 1. The Premier PINC AI database (2016-2022), a multicenter clinical database including approximately 25% of US hospitalizations was used. The analysis took place between October 6, 2023, and June 20, 2024.
Exposure Receipt of LR (intervention) or NS (control) on hospital day 1.
Main Outcome and Measures The primary outcome was hospital-free days (HFDs) by day 30. Targeted maximum likelihood estimation was used to calculate marginal effect estimates. Heterogeneity of treatment effect was explored in subgroups.
Results A total of 55 574 patient encounters where LR (n = 3495) or NS (n = 52 079) was administered on hospital day 1 were included; the median (IQR) age was 30 (25-37) years. Patients who received LR had more HFDs compared with those who received NS (marginal mean difference, 0.4; 95% CI, 0.1-0.6 days). Patients who received LR also had shorter hospital lengths of stay (marginal mean difference, −0.4; 95% CI, −0.7 to −0.1 days) and lower risk of 30-day readmission (marginal risk difference, −5.8%; 95% CI, −9.8% to −1.8%). Differences in HFDs between LR and NS were heterogenous based on fluid volume received: among patients who received less than 2 L, there was no difference in LR vs NS; among those who received 2 or more L, LR was superior to NS.
Conclusion and Relevance This cohort study found that, compared with NS, LR had a small but significant improvement in HFDs and secondary outcomes including 30-day readmission. These results suggest that, among patients with VOEs in whom clinicians plan to give volume resuscitation fluids on hospital admission, LR should be preferred over NS.
