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 administration (maitland et al, 2011)
- Administration of fluid boluses is typically done as part of a fluid challenge or to patients deemed to have fluid responsiveness
- 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 beneficial in other settings; such as severe diarrhoeal illnesses like cholera resulting hypovolaemic shock
- 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 and probably brief
- 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 interstitial space after four hours (Malbrain 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 (Malbrain 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 oedema
- acid-base disturbances
- the potential for glycocalyx injury (e.g. synthetic colloids; albumin may be protective)
- complications of intravascular access (e.g. phlebitis, CLABSI, etc)
- initial clinical and physiological improvement following fluid boluses may not lead to long-term improvement in patient-orientated outcomes (e.g. FEAST trial), in fact, 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)
- 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
Sepsis and septic shock
- There are no multi-centre 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 administered in the resuscitative phase (e.g. ARISE, PROMISE, PROCESS)
- The FEAST trial (Maitland et al, ) found that fluid bolus resuscitation had 50% higher mortality in African children with septic shock in under-resourced settings.
- Andrews et al (2017) conducted a randomised clinical trial of 212 adults with sepsis (based on SIRS criteria) and hypotension (SBP <90 mmHg or MAP <65 mmHg) from 2012-2013 in Zambia (a resource poor setting). The study showed that an early resuscitation protocol including intravenous bolus therapy had increased in-hospital mortality (48.1%) compared with usual care (33.0%) (between-group difference, 15.1% [95% CI, 2.0%-28.3%]; relative risk, 1.46 [95% CI, 1.04-2.05]; P = .03).
- The CLASSIC trial (Hjortrup et al, 2016), a multi-center pilot trial conducted in Scandinavia, found a trend toward improvement in ICU patients with septic shock who received restrictive fluids (fluids only given if signs of severe hypoperfusion). It was not powered to find a statistically significant difference in these secondary outcomes.
- Permissive hypotension was found to beneficial in a semi-randomised single centre 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 by Holcomb et al, 2015)
- Positive fluid balance associated with mortality in AKI (SOAP study), slower recovery in ARDS (FACTT trial) and morbidity in colorectal surgery patients
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 activation 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
- CCC — Critical Bleeding and Massive Transfusion
- CCC — Deresuscitation and Positive Fluid Balance
- CCC — Early Goal-Directed Therapy in Septic Shock
- CCC — FEAST and paediatric fluid resuscitation
- CCC — Fluid balance
- CCC — Fluid challenge
- CCC — Fluid responsiveness
- CCC — Glycocalyx in critical illness
- CCC — Haemostatic resuscitation
- Andrews B, Semler MW, Muchemwa L, et al. Effect of an Early Resuscitation Protocol on In-hospital Mortality Among Adults With Sepsis and Hypotension: A Randomized Clinical Trial. JAMA. 2017; 318(13):1233-1240. [pubmed]
- Bickell WH, Wall MJ Jr, Pepe PE, et al. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med. 1994 Oct 27;331(17):1105-9. [pubmed] [article]
- 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] [article]
- Durairaj L, Schmidt GA. Fluid therapy in resuscitated sepsis: less is more. Chest. 2008;133:(1)252-63. [pubmed] [article]
- 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] [article]
- Hilton AK, Bellomo R. A critique of fluid bolus resuscitation in severe sepsis. Crit Care. 2012;16:(1)302. [pubmed] [article]
- Madhusudan P, Tirupakuzhi Vijayaraghavan BK, Cove ME. Fluid resuscitation in sepsis: reexamining the paradigm. BioMed research international. 2014:984082. 2014. [pubmed] [article]
- Holcomb JB, Tilley BC, Baraniuk S, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA. 2015;313:(5)471-82. [pubmed] [article]
- Hjortrup PB, Haase N, Bundgaard H, et al. Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial. Intensive care medicine. 2016; 42(11):1695-1705. [pubmed]
- Maitland K, et al and the FEAST Trial Group. Mortality after Fluid Bolus in African Children with Severe Infection. N Engl J Med. 2011 May 26. [pubmed] [article]
- Malbrain ML, Marik PE, Witters I, et al. 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. [pubmed] [article]
Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.
After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.
He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE. He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.
His one great achievement is being the father of three amazing children.
On Twitter, he is @precordialthump.