Fluid bolus therapy

Reviewed and revised 22 July 2015

OVERVIEW

• Fluid bolus therapy is widely administered to patients with undifferentiated hypotension and for patients with severe sepsis
• The rationale and evidence base for this approach to hypotension management is controversial
• In particular, the FEAST trial found that administering fluid boluses to African children with septic shock increased mortality, despite apparent clinical improvement immediately following adminstration
• Adminstration of fluid boluses is typically done as part of a fluid challenge or to patients deemed to have fluid responsiveness

RATIONALE

• In septic shock it is inferred that the distributive shock state causes decreased preload and thus decreased cardiac output, contributing to decreased organ perfusion
• Administering fluid boluses is thought to increase blood volume, increasing venous return and cardiac output and thus organ perfusion
• Septic patients with high cardiac output states have better outcomes than those with low cardiac output states
• Fluid bolus therapy appears to beneficial in other settings; such as severe diarrhoeal illnesses like cholera resulting hypovolaemic shock

PROBLEMS

• Less than 50% of haemodynamically unstable patients are ‘fluid responders’
• it is unproven in humans that fluid boluses in septic shock improves cardiac output or organ perfusion
  • in many animal models of septic shock there is paradoxically high cardiac output and increased organ blood flow, with an absence of bio-energetic deficit — hence there may be no benefit from increasing perfusion
  • there may be other reasons why septic patients with low cardiac output states do worse than those with high output states  – e.g. they may have septic cardiomyopathy. Furthermore, conversion of a low cardiac output state to a high cardiac output state will not necessarily be beneficial. (This is a phenotype association fallacy)
• the duration of any effect of fluid boluses is uncertain
  • the physiological effects of bolus fluid resuscitation typically dissipate within 1 hour for crystalloids (longer for colloids) in animal models (Hilton et al, 2012)
  • In healthy individuals, 85% of an infused bolus of crystalloid has been reported to redistribute into the interstital space after four hours (Manu et al, 2014)
  • In critically ill patients with leaky capillaries, ~95% of an infused bolus of crystalloid leaves the circulation and enters the interstitial space after 90 minutes (Manu et al, 2014)
• fluid bolus therapy may have harmful effects:
  • positive fluid balance (associated with worse mortality in AKI, and slower recovery in ARDS)
  • impaired gas exchange (increased extravascular lung water)
  • organ and tissue edema
  • acid-base disturbances
  • potential for glycocalyx injury (e.g. synthetic colloids; albumin may be protective)
• initial clinical and physiological improvement following fluid boluses may not lead to to longterm improvement in patient-orientated outcomes (e.g. FEAST trial), infact mortality was worse! – can this be extrapolated to adults?
• probable benefits in non-haemorrhagic hypovolaemic shock (e.g. cholera) cannot be extrapolated to other settings such as sepsis (i.e. weak clinical analogy)

Alternative hypotheses

• expansion of blood volume in septic shock might increase distribution of harmful cytokines to end organs
• the hypotensive state in septic shock might be an adaptive, evolved response

EVIDENCE

Sepsis and septic shock

• there are no multi-center RCTs studying whether fluid bolus therapy should be given to critically ill patients, only studies trying to distinguish which type of fluid should be given  — it is assumed that fluid should be given. (e.g. SAFE, CHEST, and the 6S trial)
• only a few small unblinded animal studies (e.g. in rats and mice) suggest a survival benefit with fluid resuscitation; other studies have found harm (these studies are also confounded by the type of fluid used e.g. HES vs crystalloid)
• Recent trials of early goal directed therapy (EGDT) suggest that good outcomes can be achieved with <2-3L of fluid boluses administed in the resuscitative phase (e.g. ARISE, PROMISE, PROCESS)
• The FEAST trial found that fluid bolus resuscitation had 50% higher mortality in African children with septic shock in under resourced settings

Other settings

• Permissive hypotension was found to beneficial in a semi-randomised single center study of penetrating trauma patients (Bickell et al, 1999; see Permissive Hypotension) and is supported by other low level studies. Early use of blood products with a 1:1:1 ratio of PRBCs, FFP, and platelets is currently preferred (PROPPR trial)
• Positive fluid balance associated with mortality in AKI (SOAP study), slower recovery in ARDS (FACTT trial) and morbidity in colorectal surgery patients

AN APPROACH

• Fluid bolus therapy, using small boluses with frequent reassessment, is reasonable in non-haemorrhagic hypovolaemic patients with evidence of hypoperfusion
• Pending further evidence, it is reasonable to administer up to 2-3L of crystalloid to adult patients with septic shock, prior to supporting blood pressure with noradrenaline
• Patients in haemorrhagic shock should not have fluid bolus therapy, but should have active of a massive transfusion protocol with early administration of blood products (e.g. 1:1:1 ratio)
• Fluid bolus therapy should never be a reflexive action, but should be considered carefully

References and Links

Lifeinthefastlane.com

• CCC — FEAST and paediatric fluid resuscitation
• CCC — Fluid challenge
• CCC — Fluid responsiveness
• CCC — Glycocalyx in critical illness

Journal articles

• Bickell WH, Wall MJ Jr, Pepe PE, Martin RR, Ginger VF, Allen MK, Mattox KL. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med. 1994 Oct 27;331(17):1105-9. [pubmed] [free full text]
• Brandt S, Regueira T, Bracht H, et al. Effect of fluid resuscitation on mortality and organ function in experimental sepsis models. Crit Care. 2009;13:(6)R186. [pubmed] [free full text]
• Durairaj L, Schmidt GA. Fluid therapy in resuscitated sepsis: less is more. Chest. 2008;133:(1)252-63. [pubmed] [free full text]
• Glassford NJ, Eastwood GM, Bellomo R. Physiological changes after fluid bolus therapy in sepsis: a systematic review of contemporary data. Critical care. 18(6):696. 2014. [pubmed] [free full text]
• Hilton AK, Bellomo R. A critique of fluid bolus resuscitation in severe sepsis. Crit Care. 2012;16:(1)302. [pubmed] [free full text]
• Madhusudan P, Tirupakuzhi Vijayaraghavan BK, Cove ME. Fluid resuscitation in sepsis: reexamining the paradigm. BioMed research international. 2014:984082. 2014. [pubmed] [free full text]
• Malbrain ML, Marik PE, Witters I, Cordemans C, Kirkpatrick AW, Roberts DJ, Van Regenmortel N. Fluid overload, de-resuscitation, and outcomes in critically ill or injured patients: a systematic review with suggestions for clinical practice. Anaesthesiol Intensive Ther. 2014 Nov-Dec;46(5):361-80. doi: 10.5603/AIT.2014.0060. [pubmed] [free full text]