Deleterious effects of aggressive fluid resuscitation.
The harmful effects of aggressive fluid resuscitation on the outcome of sepsis are supported by experimental studies and data accumulated from clinical trials. Multiple clinical studies have demonstrated an independent association between an increasingly positive fluid balance and increased mortality in patient with sepsis. The most compelling data that fluid loading in sepsis is harmful, comes from the landmark ‘Fluid Expansion as Supportive Therapy (FEAST)’ study performed in 3141 sub-Saharan children with severe sepsis. In this randomized study, aggressive fluid loading was associated with a significantly increased risk of death. After the Rivers' Early Goal Directed Therapy trial, which formed the basis for the concept of early aggressive fluid resuscitation, a number of EGDT studies have been published.
An analysis of these studies demonstrates a marked reduction in mortality over this time period (see Fig. 1). While all these studies emphasized the early use of appropriate antibiotics, the decline in the amount of fluids administered in the first 72 h is striking. Furthermore as illustrated in Fig. 2 there is a very strong correlation between the amount of fluid administered (in first 6 h) and the target CVP. It should be noted that the CVP in the usual arm of both the ARISE (The Australasian Resuscitation in Sepsis Evaluation) and ProMISe (Protocolised Management in Sepsis) trials was greater than 10 mm Hg, being almost identical to the EGDT arm, and with almost an identical amount of fluid being administered in the usual arm, as in the active EGDT arm in both studies. Clinicians seem compelled to give fluid when the CVP is less than 8 mm Hg; the only solution to this pervasive problem is to stop measuring the CVP.
Fig 2
Fluid administered between enrolment and 72 h and 90-day mortality in the control arm of the Early Goal Directed Therapy (EGDT) Studies performed between 2001 and 2015. APACHE II=APACHE II Severity of illness scoring system (0–71).
Fig 3
Fluid administered between enrolment and 6 h and central venous pressure (CVP) at 6 h in the Early Goal Directed arm of the EGDT studies performed between 2001 and 2015.
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