Clinical Pearl 74: Why 30 ml/kg fluid bolus in Sepsis?

Recently Winters et al in a 2016 AAEM clinical practice guidelines concluded that “There is no difference in mortality between current usual care and the goal-directed approach recommended by current international guidelines for patients with severe sepsis and septic shock.”  This statement is based on the ARISE, PROMISE and PROCESS TRIALS.  As such more scientific evidence is being sought for the treatment of sepsis. The current recommendation per the “Surviving Sepsis Campaign” recommends the administration of 30 ml/kg crystalloid for hypotension or lactate > 4 mmol/L.  The Severe Sepsis 3-hour Resuscitation bundle recommends the 30 ml/kg fluid bolus therapy for the targeted guidelines are to have the CVP of ≥8 mm Hg, ScvO2 of ≥70 percent, and normalization of lactate. It is important to site there is no restriction for additional fluids but the minimal 30 ml/kg should be administered within 30-60 minutes of identification of septic patient.    There is no data to support the amount fluid resuscitation prospectively or retrospectively… only expert opinions.  Maitland et al studied pediatric patients presenting in shock in Sub-saharan Africa evaluating resuscitation with either saline or albumin compare to a no-bolus strategy in terms of all-cause mortality at 48 hours.  The Fluid Expansion as Supportive Therapy (FEAST) study published in 2011 and enrolled 3,141 Sub-Saharan children with severe febrile illness and impaired organ perfusion, and randomized them to receive either albumin, saline, or no volume resuscitation  At 48 hours, mortality was higher with albumin (10.6%) and saline (10.5%) as compared to no volume resuscitation (7.3%). Half of the participants had malaria and may not yield similar results as undifferentiated hypovolemic shock.

In the Journal of Critical Care, Hilton et al did a critique of fluid bolus in sepsis.  The author argue that 30 ml/kg has “weak physiologic support and limited experimental support.”  This interesting review for the ICU community questions why “nobody has ever challenged this dogma.”  This review cites many animal studies concluding that not even animal models show benefit for large volume fluid resuscitation. 

So if we do not have clear evidence of “help”  do we have evidence of “harm.”   The answer is yes.. in some models.  We know that fluid resuscitation boluses worsens outcome in penetrating torso trauma and positive fluid balances worsen outcome in Acute kidney injury, ARDS and recent colorectal surgery.  Also at cited above we know that NSS or Albumin in children with no significant cofounders has a 50 percent mortality increase. (FEAST STUDY)

In another 2017 study, Seethala et al evaluated the risk of developing ARDS in septic patients base on early fluid resuscitation.  2534 patients were evaluated using multivariate models.  6.2 percent of patient developed ARDS. In the first 6 hours in patients without shock, the amount of fluid resuscitation was associated with greater risk of developing ARDS 

But Why Is This? Several mechanisms exist regarding why Fluid Bolus Therapy worsens outcomes.  One model suggests rapid fluid infusion can also damage the endothelial glycocalyx leading to endothelialdisruption and organ dysfunction. Also expansion of blood volume in septic shock might increase distribution of harmful cytokines to end organs

In conclusion, of the 47 papers identified in the literature, we still have no support for 30 ml/kg.  In fact a better academic approach is to utilize repeat ultrasound evaluating the IVC, very early vasopressors, and frequent evaluations after several small bolus.  However in the true hypovolemic, hypotensive septic shock patient, fluid bolus therapy should still remain the mainstay of treatment until further randomized trials guide us.  

References:

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