Fluid management in the ICU: has the tide turned?
In 1832, Thomas Latta successfully administered intravenous fluid to patients with severe dehydration who had contracted cholera during the pandemics of the 19th century, the first recorded successful application of “saline drip” methodology . More than 150 years hence, fluid management remains a core task for clinicians in intensive care units (ICU). The indications for fluid therapy have expanded greatly and are now used not only to treat significant fluid losses, but also to avoid fluid depletion (so-called maintenance fluid) and as a means of delivering medication, electrolytes and nutrition. Perhaps the most common use of fluids in the ICU is to “optimise the circulation” in patients with suspected haemodynamic compromise. Fluid management in the ICU involves not only the management of fluid input but also the management of fluid output, including the administration of diuretics and, in the case of severe kidney failure, dialysis. Current thinking regarding fluid management might be well represented by the Surviving Sepsis Campaign guideline for continued fluid therapy beyond an initial challenge: ‘Fluid challenge technique be applied wherein fluid administration is continued as long as there is hemodynamic improvement either based on dynamic or static variables’ . The wording of this recommendation puts more emphasis on the potential benefit than the potential harm of fluids and arguably promotes the liberal use of fluids. This is in keeping with the common view of clinicians, who have tended to focus more on the risks to patients of being fluid deficient than on the risks of being fluid overloaded.
In a recent article in Intensive Care Medicine, Silversides and colleagues present the results of a systematic review and meta-analysis of fluid management beyond initial resuscitation in patients with acute respiratory distress syndrome (ARDS) and sepsis . The systematic review was performed according to high methodological standards, including a pre-published protocol . The authors chose a broad search strategy to minimise the risk of missing relevant studies and consequently screened more than 60,000 abstracts. Commendably, the meta-analysis was restricted to the randomised controlled trials (RCTs) included in the review, with observational studies still reported, albeit separately. There were also noteworthy limitations. First, most likely due to an a priori expectation of limited data from RCTs, the authors chose to include studies on both ARDS and sepsis. However, ARDS and sepsis, although not mutually exclusive, are two distinct clinical entities; as such, performing a meta-analysis of results on both clinical entities together introduces clinical heterogeneity. Additional heterogeneity is introduced with the inclusion of both adult and paediatric patient populations. Second, the concepts of ‘conservative’ and ‘liberal’ are arbitrary and varied between studies; significant differences between these strategies within the included RCTs were often not evident. Last, most of the included studies used protocols that were not reflective of daily practice where the most common indications for fluid administration are easily available measures, such as arterial blood pressure, urinary output, vasopressor dose and lactate [5, 6]. This limitation reduces the clinical applicability of trial results.
Although not unexpected, the most noteworthy aspect of the review by Silversides and colleagues was not what they found, but rather what they did not find . Despite broad inclusion criteria and a comprehensive search strategy, only 11 RCTs were included in the meta-analysis, with a median of 100 included patients. Of these, only two RCTs were performed in more than two centres [7, 8]. In their meta-analyses of the primary outcome, mortality, the authors found a relative risk of mortality for conservative versus liberal of 0.92 (95% confidence interval 0.82–1.02); albeit non-significant, this result raises concerns with the paradigm that a liberal fluid strategy is beneficial—or benign at worst. In the analysis of the secondary outcome, ventilator-free days (VFD), the authors found a significantly higher number of VFD in patients assigned to restrictive groups, a result that was mostly driven by the FACTT trial which had complex protocols in both intervention groups . A recent meta-analysis that included observational studies reported significantly lower mortality in restrictive strategies , but the results obtained by Silversides and colleagues should be regarded as more valid due to the risk of bias in observational studies—especially confounding by indication, competing risks and time-dependency.
Unanswered questions in fluid management to be addressed in future trials
Aspects of fluid management
Fluids to “optimise the circulation”
What level of circulatory impairment requires intervention with fluids and which measures of impairment are most useful?
Do fluid responders benefit from fluids?
Do fluids alleviate or cause acute kidney injury?
Do the effects of fluid depend on timing rather than indication?
Fluids to replenish losses
How to assess fluid status?
Does ‘intravascular fluid depletion’ merit fluid administration?
Fluids to maintain a fluid balance
Is maintenance fluid beneficial?
What is the minimum amount of fluid that patients should receive daily?
Fluids along other therapies (e.g. medication and nutrition)
Is it beneficial to limit fluid content?
In summary, although we are approaching the bicentennial of intravenous fluid therapy, considerable gaps in our knowledge persist. Results from observational studies and meta-analyses of RCTs suggest that liberal fluid management might be harmful to patients, but the interpretation of these results is hampered by complex protocols and substantial clinical heterogeneity. For many years, the standing paradigm in the management of the critically ill has been to ensure patients are not fluid deficient, with less attention paid to the problems related to fluid overload. This meta-analysis by Silversides and colleagues may represent the high water mark, and with the turning tide we can seek a more balanced approach to fluid management in the critically ill.
Compliance with ethical standard
Conflicts of interest
The authors have no conflicts of interest to declare.
- 2.Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, MacHado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R (2013) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 39:165–228CrossRefPubMedGoogle Scholar
- 3.Silversides JA, Major E, Ferguson AJ, Mann EE, McAuley DF, Marshall JC, Blackwood B, Fan E (2016) Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis. Intensive Care Med. doi:10.1007/s00134-016-4573-3 PubMedGoogle Scholar
- 4.Silversides JA, Ferguson AJ, McAuley DF, Blackwood B, Marshall JC, Fan E (2015) Fluid strategies and outcomes in patients with acute respiratory distress syndrome, systemic inflammatory response syndrome and sepsis: a protocol for a systematic review and meta-analysis. Syst Rev 4:162CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Cecconi M, Hofer C, Teboul JL, Pettila V, Wilkman E, Molnar Z, Della Rocca G, Aldecoa C, Artigas A, Jog S, Sander M, Spies C, Lefrant JY, De Backer D (2015) Fluid challenges in intensive care: the FENICE study: a global inception cohort study. Intensive Care Med 41:1529–1537CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Bihari S, Baldwin CE, Bersten AD, Ou J, Holt AW, Prakash S, Schnetz E, Fartasch M, van den Heuvel I, Vlasselaers D, Wouters PJ, Milants I, Ellger B, Vanhorebeek I, Van den Berghe G (2013) Post resusicitation fluid boluses in severe sepsis or septic shock: prevalence and efficacy (price study). Crit Care Resusc 12:66–70Google Scholar
- 7.Hjortrup PB, Haase N, Bundgaard H, Thomsen SL, Winding R, Pettila V, Aaen A, Lodahl D, Berthelsen RE, Christensen H, Madsen MB, Winkel P, Wetterslev J, Perner A, CLASSIC Trial Group; Scandinavian Critical Care Trials Group (2016) Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial. Intensive Care Med 42:1695–1705. doi:10.1007/s00134-016-4500-7 CrossRefPubMedGoogle Scholar
- 8.National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL (2006) Comparison of two fluid-management strategies in acute lung injury. N Eng J Med 354(24):2564–2575Google Scholar
- 9.Malbrain ML, Marik PE, Witters I, Cordemans C, Kirkpatrick AW, Roberts DJ, Van Regenmortel N (2014) Fluid overload, de-resuscitation, and outcomes in critically ill or injured patients: a systematic review with suggestions for clinical practice. Anaesthesiol Intensive Ther 46:361–380CrossRefPubMedGoogle Scholar
- 10.The ARISE Investigators and the ANZICS Clinical Trials Group (2014) Goal-directed resuscitation for patients with early septic shock. N Engl J Med 371:1496–1506Google Scholar
- 11.The ProCESS Investigators (2014) A randomized trial of protocol-based care for early septic shock. N Engl J Med 370:1683–1693Google Scholar
- 13.Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, Nyeko R, Mtove G, Reyburn H, Lang T, Brent B, Evans JA, Tibenderana JK, Crawley J, Russell EC, Levin M, Babiker AG, Gibb DM (2011) Mortality after fluid bolus in African children with severe infection. N Engl J Med 364:2483–2495CrossRefPubMedGoogle Scholar