May 17, 2016


Intravenous fluids are the most prescribed therapy in emergency and critical care settings. Fluid resuscitation is the basis of management of shock, particularly in septic shock cases[1]. The rationale of fluids use is their ability to expand intravascular volume, thus increasing mean systemic filling pressure (Pmsf) and cardiac preload and, finally, cardiac output in those patients who are in the steep part of Frank-Starling curve[2]. Distributive and hypovolemic shock may require big amounts of fluid to restore haemodynamics, however excessive fluid balance has been related to higher mortality in different studies[3, 4]. The introduction in clinical practice of some tools to explore fluid responsiveness before fluid expansion may reduce the number of patients receiving fluids inappropriately[5].

Recently Aya et al. [6], have reported the results of an observational study in which the authors tried to assess the effects of fluid administration on haemodynamics in post-operative patients. Twenty-six patients with fifty fluid challenges were finally included in the study. No baseline difference between fluid responders and non-fluid responders were present. Interestingly, neither cardiac output (CO), nor CVP or Pmsf analogue (Pmsfa) were different between groups, though a trend towards lower values in responders was evident, but not significant. Study protocol consisted in a fluid challenge of 250 mL of Hartmann solution infused over 5 minutes. CO was measured with calibrated Lidcoplus system and Pmsfa was estimated with Navigator software based on CO, CVP and mean arterial pressure (MAP). A complex statistical analysis was adopted to account for pharmacodynamics outcomes. Half of the included patients were identified as fluid responder after fluid challenge (CO increase of at least 10%). Maximal effect on CO was observed 1.2 minutes after the end of infusion in responders (95% credible interval -0.6 to 2.8 min) and it happened faster than in non responders (estimated difference -2.61 min, 95% credible interval -4.86 to -0.39 min). Also, the maximal effect on CO was greater in responders. The global effect on Pmsfa was similar, although responders achieved maximal Pmsfa faster (–1.23 min, 95% credible interval –3.21 to 0.72min). Finally, after a 10-minutes interval, effect of fluid bolus was dissipated in both groups.

This paper highlights what are the effects of fluids infusion after their administration and, for the first time, it defines also a time-window to evaluate the maximal effect of fluids on CO variation.  This is extremely important because different time points have been used to define CO, so far, yielding possibly different results in terms of identification of responders and non-responders. Furthermore, this study shows that fluid effect on hemodynamic is transient. Redistribution of water and electrolytes in the third space, and a possible increase in vascular bed compliance after initial bolus, may explain the observed reduction in Pmsfa and CVP, with consequent reduction of CO to baseline values. This implies that is very difficult to foresee how many fluids are needed to assure a persistent increase in CO and if some fluids might be more ‘effective’ than others (i.e. albumin vs. crystalloids) remains unknown. Finally, this study investigates haemodynamic variables behavior after fluid infusion in post-operative patients, leaving open the problem regarding patients in shock and particularly in septic shock, where an increase in vascular permeability and microcirculatory alterations may further complicate the whole picture.

In conclusion, Aya et al. showed that fluid challenge has a transitory effect on haemodynamic variables in responders, suggesting that fluid challenge and fluid administration should be carefully tailored on each patient, keeping in mind the possible detrimental effect of excessive volume load on organ oedema, which may affect organ impairment and, finally, patient outcome.

Article review was submitted by ESICM Journal Review Club member Antonio Dell’Anna.


1.    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, Surviving Sepsis Campaign Guidelines Committee including The Pediatric S, (2013) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive care medicine 39: 165-228
2.    Marik PE, (2015) Fluid Responsiveness and the Six Guiding Principles of Fluid Resuscitation. Critical care medicine
3.    Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA, (2011) Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Critical care medicine 39: 259-265
4.    Acheampong A, Vincent JL, (2015) A positive fluid balance is an independent prognostic factor in patients with sepsis. Critical care 19: 251
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 medicine
6.    Aya HD, Ster IC, Fletcher N, Grounds RM, Rhodes A, Cecconi M, (2016) Pharmacodynamic Analysis of a Fluid Challenge. Critical care medicine 44: 880-891

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