In a multicenter, randomized, double-blind trial comparing 0.9% saline or 4% albumin for fluid resuscitation in 6997 critically ill patients in the ICU, there was no difference in mortality (729 v 726, RR 0.99; 95 CI 0.91 to 1.09; P=0.87), new single-organ and multiple-organ failure (P=0.85), mean (SD) numbers of ICU days (6.2±6.2 v 6.5±6.6, P=0.44), hospital days (15.6±9.6 v 15.3±9.6; P=0.30), days of mechanical ventilation (4.3±5.7 v 4.5±6.1; P=0.74), or days of renal-replacement therapy (0.4±2.0 v 0.5±2.3) respectively
In a blinded randomized controlled trial comparing 6% hydroxyethyl starch 130/0.42 (Voluven) with 0.9% saline for fluid resusciation in 7000 critically ill patients, this colloid therapy was associated with a 21% increased risk of the requirement for renal replacement therapy ( HES RRT requirement 7.0% versus saline 5.8%; relative risk 1.21; 95% CI 1.00 to 1.45; P=0.04 and no mortality benefit (HES mortality 18.0% versus saline mortality 17.0%; relative risk in the HES group, 1.06; 95% CI 0.96 to 1.18; P=0.26). Starch therapy was also associated with increased rates of hepatic failure, rash and pruritus.
3. Maitland. Mortality after Fluid Bolus in African Children with Severe Infection (FEAST Trial). N Engl J Med 2011;364:2483-2495 (Paediatric Study)
Maitland et al performed a stratified (severe hypotension or not), multicenter, randomized control trial, in a resource-limited setting in sub-Saharan Africa, comparing a fluid bolus (20 to 40 ml of 5% albumin or 0.9% saline) with no fluid bolus at admission to hospital in 3,141 children with febrile illness and impaired perfusion, and found fluid bolus therapy was associated with a higher mortality at 48 hours (albumin 10.6%, saline 10.5%, no bolus 7.3%; relative risk bolus therapy versus no bolus 1.45, 95% CI 1.13 to 1.86, P=0.003), and 28 days (12.2%, 12.0% & 8.7%, respectively; RR bolus therapy versus no bolus p=0.004), with similar incidences of pulmonary oedema, increased intracranial pressure (2.6%, 2.2% versus 1.7% P=0.17), and neurological sequela in the three groups (P=0.92).
Albumin vs. Crystalloid:
Current Guidelines
2012 - Adult Surviving Sepsis Campaign
"Crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock"
"Use of albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids"
"Substantial amounts" is undefined in the guideline
2012 - Pediatric Surviving Sepsis Campaign
"...initial resuscitation of hypovolemic shock begins with infusion of isotonic crystalloids or albumin..."
So the guidelines are unclear when to use one over the other...
Recent Meta-analyses
2011 - The Role of Albumin as a Resuscitation Fluid for Pts with Sepsis (Critical Care Med)
Methods
Meta-analysis of 17 RCTs (total of 1977 pts, 14 adult and 3 pediatric trials) comparing albumin with other fluids (NS, LR, starches, gelatin) for resuscitation in sepsis
Included trials available up to 2010
Results
Albumin reduced mortality in all age groups when...
Compared to all types of fluids (OR 0.82, p = 0.05)
Compared to crystalloids only (OR 0.78, p = 0.04)
Concentrated albumin (20% or greater albumin) increased mortality in all age groups when...
Compared to all types of fluids (OR 1.08, p = 0.73)
Diluted albumin (4-5% albumin) reduced mortality in all age groups when...
Compared to all types of fluids (OR 0.76, p = 0.02)
Albumin reduced mortality in pediatric population when...
Compared to all types of fluids (OR 0.29, p = 0.008)
Albumin reduced mortality in adult population when...
Compared to all types of fluids (OR 0.87, p = 0.18)
Bottom line
Trend towards reduced mortality in children and adults when using albumin
Do not use boluses of concentrated albumin (25% albumin at U of M)
Peds population seems to like albumin, but only based on 3 small trials
2013 - Colloids vs. Crystalloids for Fluid Resuscitation in Critically Ill Pts (Cochrane Review)
Methods
Meta-analysis of 24 RCTs (total of 9920 pts who were ill due to trauma, burns, surgery, sepsis, excluding neonates and pregnant women) comparing colloids (albumin, plasma) to crystalloids (isotonic, hypertonic)
Included trials available up to 2012
Results
No difference in mortality (OR 1.01, CI 0.93-1.10)
Bottom line
No mortality benefit for resuscitation with albumin/plasma
Recent RCT Not Included in the Above Meta-analyses
2013 - Effects of FLuid Resuscitation with Colloids vs. Crystalloids in Hypovolemic Shock (JAMA)
Methods
European study performed at 57 ICUs
Adult pts with hypovolemic shock from sepsis, trauma, or other causes randomized to cyrstalloids (isotonic or hypotonic saline) vs. colloids (hypo-oncotic [gelatins, 4-5% albumin] or hyper-oncotic [dextrans, hydroxyethyl starches, 20-25% albumin])
All MIVF were isotonic saline
If pts became hypoalbuminemic (albumin <2.0), then they could receive albumin regardless of treatment group
Results
1414 pts in colloid group, 1443 pts in crystalloid group
No difference in baseline characteristics
16% of pts in crystalloid group received albumin supp
No difference in total amount of blood products transfused
No difference in proportion of pts who received renal replacement therapy (RRT)
28 day mortality (colloid vs. crystalloid) [NS = non-significant]
In all group: 25.4% vs. 27% (NS)
Just for sepsis: 27.8% vs. 29.0% (NS)
Just for albumin vs. NS: 30.0% vs. 26.6% (NS)
Just for albumin vs. NS in sepsis: 27% vs. 28.2% (NS)
90 day mortality (colloid vs. crystalloid)
In all groups: 30.7% vs. 34.2% (p = 0.03)
Just for sepsis: 32.6% vs. 36.7% (NS)
Just for albumin vs. NS: 35.0% vs. 33.4% (NS)
Just for albumin vs. NS in sepsis: 37.3% vs. 35.4% (NS)
Colloid group had more days free of...
Mechanical ventilation
Vasopressor
No difference between groups in days free of...
RRT
Low SOFA score
ICU or hospital stay
Bottom line
No short-term mortality difference in using colloids over crystalloids in septic and other hypovolemic pts
Colloids associated with better long-term mortality, but no difference when comparing albumin to NS or when comparing colloids to crystalloids in septic pts
Colloids seem to reduce days on mechanical ventilation or vasopressor but does not influence the trend of overall organ failure score or length of hospital stay
Myburgh, NEJM 2013
Ideal resuscitation fluid (does not currently exist)
Increases intravascular volume
Chemical composition close to ECF
Does not accumulate in tissue
No associated metabolic/systemic effects
Cheap!
Colloid (albumin - Osmol 250, Na 148, Cl 128; semi-synthetic - varies)
Increases oncotic pressure
Remains in the intravascular space
Requires less volume compared to crystalloids to maintain intravascular volume
Expensive
Crystalloid (NS- Osmol 308, Na 154, Cl 154; LR - Osmol 281, Na 131, Cl 111, K/Ca/lactate)
Affects tonicity of fluid
Cheap
Can lead to interstitial edema
Can lead to hyperchloremic metabolic acidosis --> possible immune and renal dysfunction
Evidence of Benefit/Harm of Various Fluids
Colloids vs. Crystalloids
1998: meta-analysis on albumin vs. crystalloids in hypovolemic, burn, or hypoalbuminemic pts
Albumin associated with increase in rate of death
2004: RCT on 4% albumin vs. saline in ICU pts (SAFE study mentioned by Dr. Annich)
No difference in death or organ failure at 28 days
2007: Subanalysis of 2004 study
Increased rate of death in TBI pts with albumin (likely elevates ICP)
Decreased risk of death in severely septic pts with albumin
No difference in death in hypoalbuminemic pts with albumin vs. saline
No difference in MAP or HR endpoint with albumin vs. saline but required less volume of albumin for resuscitation
2011: RCT on boluses of albumin or saline vs. no boluses of albumin or saline in children
Bolus albumin vs. saline had equal mortality rate at 48 hours
"Bolus albumin or saline" had higher mortality at 48 hours compared to "no bolus albumin or saline"
Cause of death was CV collapse (potential interaction between bolus'ing and compensatory neurohormonal response?)
Semi-synthetic Colloids vs. Crystalloids
Since we don't use this, I'll keep this section short
Increased rate of death and CRRT with semi-synthetic
No difference in hemodynamic resuscitation end points
Hypertonic Saline vs. Normal Saline
2004: RCT on "small volume" resuscitation with hypertonic saline vs. normal saline in TBI pts --> no short/long-term benefits
Chloride Restrictive Fluid vs. Chloride Rich Fluid
2012: RCT of Cl low fluid (LR, chloride poor albumin, plasmalyte) vs. Cl high fluid (NS, albumin, semi-synthetic) in ICU --> decreased incidence of AKI and CRRT
In summary
NS for hypovolemic and alkalotic pts
Consider albumin for early resuscitation of severely septic pts
Do not use albumin for TBI pts
Semi-synthetic fluids = FAIL
Perhaps we should be using LR rather than NS...can it be that surgeons were actually correct all this time?
This idea was further strengthened by the most recent study looking at the choice of crystalloid fluid published in CCM this year