Intravenous Fluid Replacement Therapy and Hospital Outcomes for Vaso-Occlusive Episodes in Patients with Sickle Cell Disease

Background: Vaso-occlusive event (VOE) is the most common reason for hospitalization in pediatric patients with sickle cell disease (SCD) and can cause significant morbidity and mortality. Fluid replacement in patients with VOE can reduce the sickling process and volume replete, however clinical practices regarding fluid therapy in SCD vary across different institutions. A large contributor to this variation is the lack of evidence surrounding the amount, rate, or type of fluid that should be used during a pain crisis episode. The goal of this retrospective analysis is to examine the relationship of average amount of fluid replacement with length of hospitalization and risk for adverse events, such as acute chest syndrome (ACS), transfer to the pediatric intensive care unit (ICU) and readmission (within 4 weeks from previous admission), at a large academic institution. Our hypothesis is that excessive fluid therapy prolongs hospital length of stay (HLOS) and increases risk for the aforementioned adverse events.

Methods: This was a retrospective analysis from a single center between January 2015 and April 2020. Patients with SCD (HbSS, HbSC, HbS-β⁰ thalassemia, or HbS-β⁺ thalassemia), aged 0- 30 years, with consecutive admissions hospitalized for VOE were included after local IRB approval. Records were reviewed for demographic variables such as age and gender, as well as clinical parameters, such as intravenous fluid therapy, tonicity, total fluid amount, medical history, intravenous pain medication, oral pain medication, and treatment during hospitalization.

Results: A total of 617 hospitalizations in 162 patients were included in this study. One hundred forty-one (22.9%) of the 617 hospitalizations experienced ACS; and in 55 (9%) of these hospitalizations, ACS developed during the hospital stay. Fifteen (2.4%) of the 617 hospitalizations required transfer to the pediatric ICU; 7 of the 15 hospitalizations required transfer for exchange transfusion, 7 required transfer for acute hypoxemic respiratory failure, and 1 for hypertension. One hundred twenty-one (19.7%) of the 617 hospitalizations required readmission within four weeks of their previous admission.

A Pearson correlation coefficient assessing the relationship between HLOS (days) and average IV fluid over admission (ml/kg/day) showed that more IV fluid therapy was associated with shorter HLOS (r = -0.140 and p = < 0.01). In a univariate analysis, oxygen requirement, acute chest syndrome, ICU transfer, readmission within four weeks, history of chronic pain, treatment with hydroxyurea, not receiving a normal saline bolus, and requiring a transfusion were associated with a prolonged hospital stay (p = < 0.05). A multivariable linear regression showed that ICU transfer, readmission within four weeks, history of chronic pain, treatment with hydroxyurea and requiring a transfusion were significantly associated with a prolonged hospital stay. Moreover, oxygen requirement and requiring a transfusion were significantly associated with developing ACS during their hospitalization (OR=11.094, 95% CI=5.32, 23.15) and (OR=4.69, 95% CI= 2.18, 10.09), respectively. Chronic pain was significantly associated with readmission within four weeks (OR=6.40, 95% CI=3.84, 10.65).

Conclusions: This retrospective study suggests that IV fluid therapy was associated with shorter HLOS and lower incidence of complications such as ACS. However, clinical parameters such as chronic pain and treatment with hydroxyurea were associated with prolonged LOS. These results differ from previous studies and highlight the need for prospective multicenter studies to clarify the relationship between IV fluid therapy, HLOS and adverse events in patients with sickle cell disease.

Badawy:Pfizer Inc: Research Funding; Bristol-Myers Squibb (BMS): Consultancy; CHIESI Farmaceutici S.p.A: Consultancy; Forma Therapeutics: Consultancy; Global Blood Therapeutics: Consultancy; Vertex Pharmaceuticals Inc: Consultancy; Sanofi: Consultancy; Bluebird Bio Inc: Consultancy.