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Use of lactated Ringer solution for fluid resuscitation among patients with sickle cell disease (SCD) and vaso-occlusive episodes was associated with a small -- but significant -- improvement in outcomes compared with use of normal saline, a retrospective cohort study suggested.

In the cohort of over 55,000 patient encounters, patients who received lactated Ringer solution had more hospital-free days compared with those who received normal saline (marginal mean difference 0.4 days, 95% CI 0.1-0.6), reported Nicholas Bosch, MD, MSc, of the Boston University Chobanian & Avedisian School of Medicine, and colleagues.

Patients who received lactated Ringer solution also had a shorter hospital length of stay (marginal mean difference -0.4 days, 95% CI -0.7 to -0.1) and a lower risk of 30-day readmission (marginal risk difference -5.8%, 95% CI -9.8 to -1.8), they wrote in .

Bosch and colleagues pointed out that to detect a difference in hospital-free days comparable to that identified in this study, a randomized clinical trial (RCT) would require a sample size of more than 3,500 participants.

"To our knowledge, no prior RCT of patients with SCD has enrolled a study population even half as large as that needed to confirm our findings and there have been no prior RCTs evaluating fluid therapy during VOEs [vaso-occlusive episodes]," they wrote. "In the setting of limited current evidence and where a future RCT is likely infeasible, our results support the use of [lactated Ringer] over [normal saline] for early fluid resuscitation in patients hospitalized with SCD VOEs."

The authors used a large U.S. multicenter cohort and target trial emulation to emulate a clinical trial that would enroll patients with SCD on the day of admission for management of a VOE, randomize them to immediate fluid resuscitation with lactated Ringer or normal saline solution, and follow them from enrollment to hospital discharge or for 30 days (whichever came first) to compare the average number of hospital-free days between treatment.

In explaining the rationale behind the study, Bosch and colleagues noted that SCD patients admitted for a VOE are often treated with intravenous fluid therapy to help reduce erythrocyte sickling. VOEs may be further complicated by hypovolemia and metabolic acidosis, both of which may exacerbate erythrocyte sickling.

"Thus, it is important to provide adequate fluid resuscitation that minimizes risk for metabolic acidosis in patients with VOEs," they wrote.

Emerging evidence has suggested that fluid resuscitation with balanced (e.g., lactated Ringer) rather than unbalanced (e.g., normal [0.9%] saline) solutions decreases the risks of hyperchloremic metabolic acidosis and potentially mortality in all hospitalized patients, not just those with SCD, they explained. In addition, normal saline may promote microvascular environments that predispose to erythrocyte sickling.

In a , A. Parker Ruhl, MD, MHS, of the NIH, and colleagues noted that while the results of the study showed small improvements in hospital-free days with lactated Ringer solution, whether these differences meet a minimal clinically important difference threshold has not been determined, particularly since no differences in mortality or other clinically relevant outcomes were reported in the study.

"Its findings direct us to redouble our scientific efforts to better elucidate the underlying mechanisms and pathophysiology of erythrocyte sickling and endothelial adhesion and how they interact to affect vaso-occlusion and vascular function," they wrote. "Together, these studies would give us the needed insights to define a conceptual model regarding the effect of IV fluid type on SCD pathophysiology and clinical outcomes."

For this study, Bosch and colleagues used an enhanced claims database including approximately 25% of U.S. hospitalizations from January 2016 to September 2022. A total of 55,574 patient encounters (15,798 patients) were included in the final study cohort -- 3,495 who received lactated Ringer solution and 52,079 who received normal saline.

Median patient age was 30 years, 54.7% were women, and 92.1% were Black. Of these patients, 85.1% had HbSS genotype, and 6.6% had acute chest syndrome present on admission.

Bosch and colleagues found that associations between lactated Ringer versus normal saline solution and hospital-free days varied depending on the volume of fluid received on hospital day 1, and possibly HbSS genotype.

There was no difference between groups for patients who received less than 2 L of fluid, but lactated Ringer solution was superior to normal saline for those who received ≥2 L. In patients with HbSS genotype, lactated Ringer solution was superior to normal saline, while there was no difference among patients without HbSS genotype.

Overall, there were also no differences in organ support-free days between the two groups (marginal mean difference 0.1 day, 95% CI -0.03 to 0.20), as well as blood transfusion-free days (marginal mean difference 0.1 day, 95% CI -0.05 to 0.3), hospital mortality (marginal absolute risk difference -0.2, 95% CI -0.6 to 0.1) or intravenous diuretic use (marginal absolute risk difference -1.2, 95% CI -2.9 to 0.5).

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