were administered perioperatively . 12 The risk of fluid overload was investigated in an observational cohort study in 730 ICUs in 84 countries comprising 1808 patients with an admission diagnosis of sepsis . 13 Fluid balance on days 1 and 3 was assessed in survivors and non-survivors . A higher cumulative fluid balance at day 3 , but not in the first 24 hours after ICU admission , was independently associated with an increase in the hazard of death . 13
Large volume fluid resuscitation is currently viewed as the cornerstone of the treatment of septic shock . The Surviving Sepsis Campaign ( SSC ) guidelines strongly recommend rapid administration of a minimum of 30ml / kg crystalloid solution intravenously to all patients with septic shock and to those with elevated blood lactate levels . 14
The European Society of Intensive Care Medicine ( ESICM ) questions oliguria as a trigger for fluid therapy , because fluid contributes to a positive fluid balance that worsens AKI and it is unknown if predictive markers of fluid responsiveness are related to improved outcomes . 3 In volume resuscitation , too little fluid leads to hypovolaemia , and too much fluid to hypervolaemia , which can lead to oedema , intrabdominal hypertension , respiratory failure , impaired healing , altered mobilisation and multiorgan failure . Complications of hypovolaemia include altered tissue perfusion , renal failure , anastomosis leakage , confusion and risk of cerebrovascular accidents , splanchnic ischemia , and also multiorgan failure . 15 Both capillary leakage and hypo-oncocity contribute to oedema formation . 16
State-of-the-art fluid therapy In the initial phase of volume resuscitation following septic shock , administration of 500ml to 1l of crystalloid fluid over a short period of less than one hour is now recommended . 17 The SSC recommendation of 30ml / kg over 3 hours means that too much fluid 18 is administered over an extended period of time . 19 Mortality in sepsis increases if vasopressor therapy is initiated after more than 2 hours after resuscitation . 20 Thus , in septic shock , if patients are hypotensive after initial fluid therapy , vasopressors should be given early . 21
Liberal and conservative approaches were studied in ARDS and sepsis . 22 According to a meta-analysis of 11 RCTs involving 2051 adults and children with ARDS , sepsis or systemic inflammatory response syndrome , a conservative or deresuscitative fluid strategy results in an increased number of ventilator-free days and a decreased length of ICU stay compared with a liberal strategy or standard care , with an unknown effect on mortality . 22 The implementation of a deresuscitative fluid strategy involves making distinctions between fluid requirement , responsiveness , and tolerance , but a significant number of patients hospitalised with severe illness still does not have a documented order for strict monitoring of fluid intake and output . 23
In the real-world , changes were observed in the type of fluids used , with more crystalloids ( more buffered solutions and less saline ) and less synthetic colloid solutions ( hydroxyethyl starch , gelatin , and dextran ), but more human albumin solutions , being
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administered than five years ago . For volume resuscitation , current ESICM consensus 3 on volume therapy recommends that :
• Fluid boluses , for example , 250 – 500ml , are used and are to be stopped if the circulation does not improve ;
• A fixed volume should be administered to substitute for documented losses ;
• Crystalloid solutions , that is , buffered solutions or isotonic saline , are recommended ;
• Artificial colloids , that is hydroxyethyl starch , gelatin or dextran solutions , should not be given ; and
• Fluid restriction and negative fluid balances should be initiated as soon as circulation has stabilised .
Use of human albumin solutions in RVIs Lower serum albumin levels at the time of patient admission are associated with increased risk of acute respiratory failure ( ARF ) requiring mechanical ventilation . 27
In infectious and inflammatory diseases , hypoalbuminaemia is a marker of transcapillary leakage . This conclusion is derived from a prospective study of 2474 patients with communityacquired bacteraemia , which measured serum albumin and C-reactive protein levels daily before , during , and after bacteraemia . A sudden decrease of albumin levels was observed without sudden fluctuations of C-reactive protein levels , which can only be explained by transcapillary leakage causing the sudden decrease . 28 Moreover , hypoalbuminaemia at admission is the strongest predictor of hospital mortality in acute medical care . 29
Hypoalbuminaemia predicts antimicrobial treatment failure Secondary bacterial infections are commonly co-identified in severe RVIs , 30 and , for this reason , standard antibacterial therapy should be initially prescribed for adults with community-acquired pneumonia who test positive for influenza . 31
However , the administration of inadequate antimicrobial treatment to critically ill patients is associated with a greater hospital mortality in the treatment of bloodstream infections , 32 and decreasing serum albumin concentrations are independently associated with the administration of inadequate antimicrobial treatment . 32
The binding of antimicrobials to albumin and plasma proteins affects the plasma concentration of these drugs and target site pharmacokinetics may be significantly altered in patients with severe hypoalbuminaemia . 33 , 34 Practice guidelines in France therefore suggest for therapy with beta-lactam antibiotic measuring albumin ( or at least plasma proteins ) at least once after initiating treatment , and also when performing beta-lactam therapeutic drug monitoring in order to guide the prescription and to help in the interpretation of the results . 35
Intravenous infusion of human albumin solution in fluid therapy Volume kinetics A study of body fluid shifts occurring when 20 % albumin is given by intravenous infusion investigated its efficacy to expand the plasma volume after major surgery . An intravenous infusion of 3ml / kg 20 % albumin over 30 minutes was given to 15 volunteers and to 15 patients on the first day after major open abdominal surgery . The rise in plasma albumin expanded the plasma volume in excess of the infused volume , by relocating noncirculating fluid in both normal volunteers and patients at a virtual steady state for almost 2 hours . There were no clinically relevant differences in the kinetics of the 20 % albumin solution between postoperative patients and volunteers . 36
Small volume resuscitation In the Small Volume Resuscitation With 20 %
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