Fluid overload in paediatric sepsis/septic shock patients tied to poor outcomes

Excessive fluid administration within the first 5 days in the paediatric intensive care unit (PICU) was consistently and independently associated with poor clinical outcomes in children with severe sepsis and septic shock, a Singapore study has shown.

“[Our findings showed] that cumulative fluid balance over the first few days of sepsis was associated with mortality … with greater harm associated with a greater magnitude of positive balance,” said the researchers.

A retrospective analysis of 116 PICU patients (median age 105.9 months, mortality rate 28.4 percent, median time to death 4 days) showed an independent association between cumulative percentage fluid overload (%FO) and increased mortality (adjusted odds ratio, 1.08, 95 percent confidence interval, 1.03–1.13; p=0.001). [Ann Acad Med Singapore 2019;48:290-297]

“[F]or every 1 percent FO increase, there was an increase in mortality by 8 percent … Patients with cumulative %FO in the range of 2.3–14.6 percent had fivefold increased odds of mortality, whereas those with >14.6 percent [cumulative %FO increased their odds by] nearly 20-fold,” said the researchers. This outcome illustrates how progressive fluid overload can worsen clinical outcomes in this setting, they added.

The link between positive fluid balance and worse clinical outcomes remained even after adjusting for severity of illness as measured by the PIM* 2 score, noted the researchers. “However, [this] finding must be interpreted in the context that there is a possibility that severity of sepsis measured by the PIM 2 score is less robust compared to the [PERSEVERE**] biomarker model.”

Fluid overload: The lowdown

Early goal-directed therapy with fluid resuscitation has been one of the cornerstones of treatment in sepsis, and guidelines have recommended fluid resuscitation for patients with sepsis to restore mean circulating filling pressure. [Ann Acad Med Singapore 2014;43:267-274; Crit Care Med 2004;32:858-873]

However, excessive fluid administration may lead to tissue oedema and impairments in oxygen and metabolite diffusion, tissue architecture, and lymphatic and capillary drainage, consequently leading to progressive organ dysfunction. [Nat Rev Nephrol 2010;6:107-115] Fluid accumulation also causes cerebral, hepatic, renal, and gastrointestinal oedema. [BMC Nephrology 2016;17:109]

Given these adverse pathophysiologic changes, as well as findings of the FEAST*** trial reflecting an association between mortality and aggressive early fluid resuscitation in children with severe febrile illness, the World Health Organization (WHO) advocates a more conservative approach to fluid resuscitation in children with severe sepsis and septic shock. [WHO updated guideline: paediatric emergency triage, assessment and treatment: care of critically-ill children, https://apps.who.int/iris/handle/10665/204463, accessed 13 November 2019] “Future studies [should evaluate] the impact of restrictive fluid strategies in this setting,” said the researchers.