Evaluating Survival Management of Patients With Ebola Virus Disease

A recent study examining Ebola virus disease survival and intravenous fluid administration brings to light broader knowledge gaps about survival management that should be studied further, according to editorial commentary published in Clinical Infectious Diseases.¹

During the 2013 to 2016 Ebola virus outbreak in West Africa, there was a glaring difference in fatality between patients who were treated in West Africa and those treated in high-income countries (case fatality ratio, 40% vs 18.5%). However, it is unclear whether supportive care, or which components of supportive care, contributed to this difference in survival. Therefore, the study performed by Alusio et al² retrospectively evaluated the relationship between intravenous fluid and survival in patients with Ebola virus disease during the West Africa 2013-2016 outbreak.

Study results showed no difference in 28-day survival between patients who did and did not receive intravenous fluid. Post hoc subgroup analyses that categorized patients by the volume of intravenous fluid administered showed that patients in the low fluid group (<20 mL/kg/day) had a greater 28-day survival than patients in the higher fluid group (³20 mL/kg/day; 35% vs 7.6%). Alusio et al concluded that their study results “provide the highest quality evidence to date that intravenous fluid, by itself, does not improve survival in patients with [Ebola virus disease].” However, limitations of this study being retrospective of observational data prevented the identification of a causal relationship between intravenous fluid administration and survival as a result of uncontrollable unknown factors.

The study brought important questions to light that justified the evaluation of supportive care components in Ebola virus disease management in future studies. Some questions included the following:

1. When evaluating intravenous fluid administration efficacy for the survival of patients with Ebola virus disease, what volume cutoff is the most clinically meaningful?

2. When administering intravenous fluid, what should the physiologic resuscitation targets be?

3. To guide Ebola virus disease management, is it appropriate to extrapolate data from intravenous fluid management trials of sepsis?

Questions about intravenous fluid management also highlight broader knowledge gaps about supportive care for patients with Ebola virus disease. For example, it is unknown whether to give antibiotics routinely to cover for gut translocation of gram-negative bacteria, how this approach may contribute to local antimicrobial resistance, or how antibiotic-related colitis or diarrhea may worsen fluid loss. Further, it is unclear whether mass drug administration for malaria or whether any antimalarial agent may affect EVD and the frequency of symptomatic coinfection.

Given the unknowns about this topic and challenges that limit retrospective analyses, Alusio et al’s retrospective evaluation provided a foundation for future analyses to address these questions. Overall, the commentary authors concluded that, “With an evolution in clinical care during [the ongoing Ebola virus disease outbreak in Democratic Republic of Congo], however, optimism should persist for deriving meaningful data on the impact of [intravenous fluid] and optimized supportive care on survival through this ongoing [randomized clinical trial]”.

References

1. Jacob ST, Brown CS. Evaluating the impact of intravenous fluid resuscitation on survival for the management of patients with Ebola virus disease [published online May 6, 2019]. Clin Infect Dis. doi:10.1093/cid/ciz349/54858462.
2. Alusio AR, Yam D, Peters JL, et al. Impact of intravenous fluid therapy on survival mong patients with ebola virus disease: an international multisite retrospective cohort study [published online May 3, 2019]. Clin Inf Dis. doi:10.1093/cid/ciz344