Research Gaps Limit Role of Intravenous Hydration for Sickle Cell Crises

Sagar Pandey, MBBS, MD

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A recent systematic review evaluated the available research on the role and utility of intravenous fluid on health outcomes among patients with sickle cell disease (SCD) admitted to the hospital with vaso-occlusive crises (VOCs).¹

The review found the available data on the safety and efficacy of intravenous fluid exists primarily in the form of isolated retrospective studies and in vitro experimental models, but there is a dearth of evidence from large-scale, well-structured clinical trials needed to guide the treatment approach.

“There remains an evidence gap regarding the standardized choice of therapy to maintain hydration in a therapeutic window along with the impact of intravenous fluid on clinical outcomes,” wrote the investigative team, led by Sagar Pandey, MBBS, MD, department of internal medicine, One Brooklyn Health System/Interfaith Medical Center.

Although considered an essential component in SCD crisis management, intravenous fluid has been linked to adverse outcomes, including fluid overload, pulmonary edema leading to ICU admission, and an increased length of stay.² Smaller-scale, retrospective studies have attempted to evaluate the outcomes of intravenous hydration but did not conclude its benefits or provide guidance on its use.

In the current review, Pandey and colleagues assessed the available evidence on the role and utility of intravenous hydration in SCD-related crises and related adverse outcomes. The team conducted a literature search in the PubMed and Google Scholar databases up until January 2024.

Poor hydration has been linked to increased plasma osmolality leading to red blood cell dehydration, increased sickled hemoglobin (HbS) polymerization, and VOCs. However, a notable complication of fluid therapy that carries the potential for significant morbidity is fluid overload.

In the review, a retrospective study investigating the incidence of fluid overload among 100 patients admitted for COV found that 21% of the population developed fluid overload over two years. There were no differences in diastolic dysfunction between those with and without fluid overload, but a history of volume overload was defined as an independent predictor for recurrence (P = .0017), while blood transfusion during admission was a significant risk factor (P = .004).

Acute painful VOC is typically the primary symptom of SCD leading to emergency room visits, hospital admissions, morbidity and mortality, and negative impacts on quality of life. Primarily managed with analgesics, the role of intravenous fluid in the management of VOC is unclear.

The review identified a study on pain scores among 400 patients with SCD presenting with SOC, who were divided into two cohorts receiving or not receiving fluid bolus in the emergency department. Based on the conclusion, significantly less improvement in pain score was identified in patients who received normal saline boluses (P = .03), and these patients experienced higher rates of inpatient admission (P = .01) and longer time spent in the emergency department (P = .01).

Another study found patients who developed fluid overload experienced significantly longer hospital stays versus those who did not (P = .037). The hospital length of stay increased by 0.5 days for each additional time the estimated weight-based maintenance fluid rate (P <.001), suggesting excessive fluid administration is associated with a prolonged hospital stay.

Further studies have reported renal, cardiac, and pulmonary complications with the use of intravenous fluid. Pandey and colleagues noted the correlation between high fluid and adverse events emphasizes the risk of aggressive fluid therapy, particularly given the underlying comprised renal and cardiopulmonary function in patients with SCD.¹

Guidelines released by the American Society of Hematology in 2020 for the management of SCD did not point to any recommendations for or against intravenous fluid in patients with sickle cell VOC.² Pandey and colleagues noted that only a single, randomized clinical trial has been conducted on the role of intravenous hydration in patients with SCD presenting with VOC.¹

However, the trial evaluated the role of warmed versus non-warmed normal saline on hospital admission rates, pain scores, disposition times, opioid dose, and comfort. All evaluated metrics were comparable between the two forms of saline, while comfort level was higher in the warmed saline cohort (P = .01).

“It is therefore imperative to conduct large-scale clinical trials to assess the role of intravenous hydration among patients with SCD presenting with VOC, not only to formulate universal treatment guidelines but also to prevent the unrestrained use of IV hydration and associated adverse outcomes,” Pandey and colleagues wrote.

References

1. _{Pandey S, Tan E S, Bellamkonda A, et al. (February 19, 2024) Intravenous Hydration and Associated Outcomes in Patients With Sickle Cell Disease Admitted With Vaso-Occlusive Crises: A Systematic Review. Cureus 16(2): e54463. doi:10.7759/cureus.54463}
2. _{Gaartman AE, Sayedi AK, Gerritsma JJ, et al. Fluid overload due to intravenous fluid therapy for vaso-occlusive crisis in sickle cell disease: incidence and risk factors. Br J Haematol. 2021;194(5):899-907. doi:10.1111/bjh.17696}
3. _{Brandow AM, Carroll CP, Creary S, et al. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain. Blood Adv. 2020;4(12):2656-2701. doi:10.1182/bloodadvances.2020001851}