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Intensive Care Med

DOI 10.1007/s00134-017-4989-4


The dark sides of fluid administration
in the critically ill patient
Daniel A. Reuter1*, Daniel Chappell2 and Azriel Perel3

© 2017 Springer-Verlag GmbH Germany, part of Springer Nature and ESICM

The administration of intravenous fluids is probably the glycocalyx lead to a pathological shift of protein-rich
most frequently initiated therapy in critically ill patients. plasma towards the interstitium, the so-called capillary
With very few exceptions, such as severe congestive heart leakage. This type of edema formation may occur even
failure, IV fluids are considered as a safe and generalistic before “hemodynamic fluid overload” [2].
therapeutic approach. Indeed, IV fluids save lives in many Dilutional coagulopathy: Fluid loading may induce
clinical situations and often the benefits outweigh the dilutional coagulopathy, which can increase the risk of
potential harm. Really? (re-)bleeding in the trauma or the surgical patient. The
All of our interventions, even those that were initially administration of cold fluids may further aggravate such
considered to have a safe therapeutic range—sooner or coagulopathy by inducing hypothermia [3].
later—revealed to have a “dark side”. In highly complex, Dilutional anemia: IV fluid administration causes a rel-
critically ill patients, these “dark sides” become even ative, but not absolute, reduction in hemoglobin concen-
more relevant, invoking therapeutic conflicts that neces- tration. Similarly, fluid accumulation may decrease serum
sitate an individual risk assessment of each decision. creatinine levels and thus lead to a delayed diagnosis or
Fluid administration often presents us with the ‘clas- underestimation of acute kidney injury. Hemodilution
sic’ therapeutic conflict, between the need for hemody- may also result in a loss of erythrocyte-filled capillaries,
namic stabilization—meaning restoration of end-organ leading to a reduction in the oxygen-carrying capacity
microcirculatory perfusion—versus the dangers of fluid and effective microcirculatory oxygen delivery with the
overload. possible development of organ dysfunction [4]. Iatrogenic
An increasing number of sub-analyses of sepsis stud- hemodilution may cause a paradoxical decrease in oxy-
ies demonstrate that aggressive fluid administration aim- gen delivery, which in turn may lead clinicians to admin-
ing to achieve CVP values even within the ‘physiological’ ister catecholamines or even more fluids. The decrease of
range, in the sickest patients in particular, turns out to be hemoglobin levels to below the transfusion threshold due
more harmful than beneficial [1]. But why? to excessive fluid loading may also trigger administration
Edema formation: The main mechanism of edema for- of blood transfusions that are potentially avoidable [5].
mation is the degradation of the endothelial glycocalyx, This may explain why patients who received more fluids
which is mainly responsible for the regulation of perme- perioperatively also received significantly more blood
ability and for fluid shifting towards the interstitial space. transfusions [6].
Even with an intact endothelial glycocalyx, there is nor- Electrolyte imbalance: All clinically applied solutions
mally a shift of protein-free fluid and electrolytes out contain un-physiological concentrations of electrolytes
of the vasculature. Only when the capacity of the lym- and, at times, artificial substances. Fluid administration
phatic system to drain this fluid shift is overwhelmed, may therefore lead to a dose-dependent electrolyte and
tissue edema occurs. During critical illness, frequently acid–base imbalance such as hyperchloremic acidosis
substantial physical and functional alterations of the and to functional, or even physical, organ damage [7].
Pathophysiological consequences: The above-men-
*Correspondence: Daniel.reuter@med.uni‑
tioned and, possibly, other side effects of excessive fluid
Department of Anesthesiology and Intensive Care Medicine, University
Medical Center, Rostock, Schillingallee 35, 18057 Rostock, Germany
Full author information is available at the end of the article
Table 1  Prevalent iatrogenic ‘dark sides’ of fluid administration
Dark side Pathophysiological mechanisms Clinical consequence

Edema formation Hydrostatic intravascular pressures ↑ Oxygen delivery to end organs↓
Destruction of endothelial glykokalix End organ dysfunction (e.g. lungs, brain, kidney, gut)
Risk for infections ↑
Risk for GI anastomotic breakdown ↑
Organ congestion Hydrostatic intravascular pressures ↑ End organ dysfunction (e.g. kidney, liver, heart)
Intra-organ/capsular/compartmental pressures ↑
Dilutional coagulopathy Relative decrease of thrombocytes and coagulation factors Risk of bleeding ↑
Hypothermia Application of cold infusions Coagulopathy ↑
Dilutional anemia Relative decrease of Hb: O2 transport capacity↓ Need for compensatory increase in CO ⇒ endogenous cat-
echolamines ↑/exogenous application of catecholamines;
need for transfusions
Electrolyte imbalance Chloride-rich infusions induce hyperchloremic acidosis End organ (kidney) dysfunction/damage

administration may cause the dysfunction of many organ patients who will sustain most harm from unnecessary
systems including the heart, lungs, kidneys, gut and fluid loading as the associated dilution may lead to a par-
brain. [8]. adoxical decrease in oxygen delivery [11]. Fluid admin-
Practical conclusions: The first step toward better fluid istration necessitates an ever-present search for signs of
management is the recognition that it needs to be physi- its “dark sides”, i.e. of fluid overload. Echocardiography,
ologically justified, individually adjusted, and critically the measurement of extravascular lung water, point-of-
questioned. We have to constantly remind ourselves of care thrombelastography, and a continuously measured
the repeatedly shown finding that only half of surgical hemoglobin which may alert the development of pos-
and critically ill patients actually respond to fluid admin- sible dilution may all be useful clinical tools in selected
istration by increasing their cardiac output (CO) [9]. Even groups of patients [3, 12, 13]. When aggressive fluid
when fluid loading does increase CO, this effect is fre- administration seems to be clinically indicated, we have
quently of short duration only, and may not necessarily to bear in mind that by the time the full extent of fluid
be accompanied by microcirculatory improvement. This overload becomes incontrovertible, it may be already too
sobering reality should make us admit how uncertain late to mount effective therapeutic measures. This means
we are regarding optimal fluid management, and should that after a justified fluid resuscitation for acute stabiliza-
serve as an incentive to assess the fluid responsiveness tion, and as soon as hemodynamically tolerable, fluid de-
status of each patient, preferably before fluids are actually resuscitation strategies should be initiated [14]. Among
administered. In mechanically ventilated patients, the other beneficial effects, such fluid removal may facilitate
information supplied by continuous dynamic parameters weaning from mechanical ventilation [15].
like the PPV, SVV, and PVI may be helpful, when appro- In conclusion, we have to realize that fluid administra-
priate [10]. Other intermittent dynamic parameters, tion has very real and prevalent iatrogenic ‘dark sides’
like passive leg raising, may be helpful in some circum- (Table  1). In order to minimize the occurrence of fluid
stances, though continuous CO has to be measured in overload and minimize its deleterious effects, we need
order to get a reliable result. Multiparametric, automated to either prevent it or identify it as early as possible.
analysis of physiological variables derived from hemody- When the risk associated with possible fluid overload is
namics, ventilation and other modalities will hopefully increased in the individual patient, more focused moni-
further increase accuracy in the detection of fluid respon- toring efforts should be employed. Or, with the words of
siveness. When still in doubt, and especially in patients Yoda in Star Wars III, the Revenge of the Sith: “In a dark
where an error may be detrimental, a low-volume fluid place we find ourselves and a little more knowledge lights
challenge should be administered, again under CO moni- our way”.
toring, as the response of the blood pressure, heart rate
and CVP alone can often be misleading. A status of fluid
Author details
responsiveness per se does not automatically mean that 1
 Department of Anesthesiology and Intensive Care Medicine, University
fluids should be administered. However, the most impor- Medical Center, Rostock, Schillingallee 35, 18057 Rostock, Germany. 2 Depart-
tant aspect in the assessment of fluid responsiveness is ment of Anesthesiology, Ludwig Maximilians University, University Hospital
Munich, Munich, Germany. 3 Department of Anesthesiology and Intensive
the identification of fluid ‘non-responders’. These are the Care, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel.
Received: 9 September 2017 Accepted: 31 October 2017 9. Michard F, Teboul JL (2002) Predicting fluid responsiveness in ICU
patients: a critical analysis of the evidence. Chest 121:2000–2008
10. Cecconi M, De Backer D, Antonelli M, Beale R, Bakker J, Hofer C et al
(2014) Consensus on circulatory shock and hemodynamic monitoring.
Task force of the European Society of Intensive Care Medicine. Intensive
Care Med 40:1795–1815
References 11. Monnet X, Julien F, Ait-Hamou N, Lequoy M, Gosset C, Jozwiak M et al
1. Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips (2013) Lactate and venoarterial carbon dioxide difference/arterial-venous
GS et al (2017) Time to treatment and mortality during mandated emer- oxygen difference ratio, but not central venous oxygen saturation, pre-
gency care for sepsis. N Engl J Med 376:2235–2244 dict increase in oxygen consumption in fluid responders. Crit Care Med
2. Chappell D, Jacob M (2014) Role of the glycocalyx in fluid management: 41:1412–1420
small things matter. Best Pract Res Clin Anaesthesiol 28:227–234 12. Assaad S, Shelley B, Perrino A (2017) Transpulmonary thermodilution: its
3. Kozek-Langenecker SA, Ahmed AB, Afshari A, Albaladejo P, Aldecoa C, role in assessment of lung water and pulmonary edema. J Cardiothorac
Barauskas G et al (2017) Management of severe perioperative bleeding: Vasc Anesth 31:1471–1480
guidelines from the European Society of Anaesthesiology: first update 13. El Hadouti Y, Valencia L, Becerra A, Rodríguez-Pérez A, Vincent JL (2017)
2016. Eur J Anaesthesiol 34:332–395 Echocardiography and passive leg raising in the postoperative period. A
4. Ince C (2015) Hemodynamic coherence and the rationale for monitoring prospective observational study. Eur J Anaesthesiol 34:748–754
the microcirculation. Crit Care 19:S8 14. Malbrain ML, Marik PE, Witters I, Cordemans C, Kirkpatrick AW, Roberts DJ
5. Perel A (2017) Iatrogenic hemodilution: a possible cause for avoidable et al (2014) Fluid overload, de-resuscitation, and outcomes in critically
blood transfusions? Crit Care (in press) ill or injured patients: a systematic review with suggestions for clinical
6. Ackland GL, Iqbal S, Paredes LG, Toner A, Lyness C, Jenkins N et al (2015) practice. Anaesthesiol Intensive Ther 46:361–380
Individualised oxygen delivery targeted haemodynamic therapy in high- 15. Liu J, Shen F, Teboul JL, Anguel N, Beurton A, Bezaz N et al (2016) Cardiac
risk surgical patients: a multicentre, randomised, double-blind, controlled, dysfunction induced by weaning from mechanical ventilation: incidence,
mechanistic trial. Lancet Resp Med 3:33–41 risk factors, and effects of fluid removal. Crit Care 20:369
7. Sen A, Keener CM, Sileanu FE, Foldes E, Clermont G, Murugan R et al
(2017) Chloride content of fluids used for large-volume resuscitation is
associated with reduced survival. Crit Care Med 45:e146–e153
8. Tsui AK, Dattani ND, Marsden PA, El-Beheiry MH, Grocott HP, Liu E et al
(2010) Reassessing the risk of hemodilutional anemia: some new pieces
to an old puzzle. Can J Anesth 57:779–791