Albumin Improves Organ Function In Critically Ill Hypoalbuminemic Patients
Albumin Improves Organ Function In Critically Ill Hypoalbuminemic Patients
Objective: To test the hypothesis that administration of albumin to correct hypoalbuminemia might have beneficial effects on organ function in a mixed population of critically ill patients.
Design: Prospective, controlled, randomized study.
Setting: Thirty-one-bed, mixed medicosurgical department of intensive care.
Patients: All adult patients with a serum albumin concentration =30 g/L were assessed for eligibility. Principal exclusion criteria were expected length of stay <72 hrs, life expectancy <3 months or a do-not-resuscitate order, albumin administration in the preceding 24 hrs, or evidence of fluid overload.
Interventions: The 100 patients were randomized to receive 300 mL of 20% albumin solution on the first day, then 200 mL/day provided their serum albumin concentration was <31 g/dL (albumin group), or to receive no albumin (control group).
Measurements and Main Results: The primary outcome was the effect of albumin administration on organ function as assessed by a delta Sequential Organ Failure Assessment score from day 1 to day 7 (or the day of intensive care discharge or death, whichever came first). The two groups of 50 patients were comparable at baseline for age, gender, albumin concentration, and Acute Physiology and Chronic Health Evaluation II score. Albumin concentration did not change over time in the control group but increased consistently in the albumin group (p < .001). Organ function improved more in the albumin than in the control group (p = .026), mainly due to a difference in respiratory, cardiovascular, and central nervous system components of the Sequential Organ Failure Assessment score. Diuretic use was identical in both groups, but mean fluid gain was almost three times higher in the control group (1679 ± 1156 vs. 658 ± 1101 mL, p = .04). Median daily calorie intake was higher in the albumin than in the control group (1122 [935-1158] vs. 760 [571-1077] kcal, p = .05).
Conclusions: Albumin administration may improve organ function in hypoalbuminemic critically ill patients. It results in a less positive fluid balance and a better tolerance to enteral feeding.
Hypoalbuminemia occurs commonly in the intensive care unit (ICU) and may be due to decreased synthesis by the liver and/or to increased losses, either internally (in the interstitium as a result of increased capillary permeability) or externally (through blood losses or exudates or increased proteolysis and clearance). The administration of albumin solutions to correct hypoalbuminemia has been debated over the years as it is not clear if hypoalbuminemia is simply a marker of the severity of disease or is causally linked to the development of complications. Moreover, albumin administration may have deleterious effects including altered coagulation, altered renal function, decreased myocardial contractility, immunosuppression, and worsened edema due to the passage of albumin into the interstitial compartment.
The now famous Cochrane meta-analysis of clinical trials addressing albumin administration in the critically ill indicated that the relative risk of death after albumin administration was 1.68 (95% confidence interval 1.26-2.23) in all patients and 1.69 (1.07-2.67) in hypoalbuminemic patients. A more recent meta-analysis on albumin administration showed no increased mortality rate in patients regardless of the indication for receiving it, although a recent observational study of 3,147 acutely ill patients reported that albumin administration was independently associated with a lower 30-day survival, using a Cox proportional hazard model, and that, in 339 pairs matched according to a propensity score, ICU and hospital mortality rates were higher in patients who received albumin than in those who did not. However, the Saline vs. Albumin Fluid Evaluation (SAFE) study, an Australian randomized controlled trial that recruited >7,000 patients, showed no differences in outcome between patients treated with 4% albumin as their resuscitation fluid and those receiving saline.
The question of whether to administer albumin in hypoalbuminemic patients, however, remains largely unanswered. It is difficult to imagine how hypoalbuminemia could be beneficial. For example, hypoproteinemia has been shown to correlate with the development of acute respiratory distress syndrome and other complications, and hypoalbuminemia has been associated with worse outcomes from cardiac surgery. Indeed, a meta-analysis of 90 cohort studies and nine prospective controlled studies showed that hypoalbuminemia was an independent predictor of poor outcome. This association between hypoalbuminemia and poor outcome appeared to be independent of both nutritional status and inflammation. Analysis of serum albumin concentration in the controlled trials of albumin therapy suggested that complication rates may be reduced when the serum albumin concentration reached during albumin administration exceeds 30 g/L. Also of concern is that mortality, the usual end point of these trials, may be insensitive in a critical care setting, and many have argued that morbidity may be a more sensitive end point. In a recent multiple-center trial, 40 mechanically ventilated patients with acute lung injury or acute respiratory distress syndrome who had total protein concentrations <6.0 g/dL were randomized to receive furosemide with placebo or furosemide with albumin for 72 hrs. Patients who received albumin had improved oxygenation, with greater net negative fluid balance and better maintenance of hemodynamic stability.
In this pilot study, we used the concept of delta Sequential Organ Failure Assessment (SOFA), recently also used to assess effects of activated protein C on organ function in patients of the PROWESS study, to assess the effects of albumin therapy on morbidity, and we prospectively tested the hypothesis that administration of albumin to correct hypoalbuminemia might have beneficial effects on organ function in a mixed population of critically ill patients.
Abstract and Introduction
Abstract
Objective: To test the hypothesis that administration of albumin to correct hypoalbuminemia might have beneficial effects on organ function in a mixed population of critically ill patients.
Design: Prospective, controlled, randomized study.
Setting: Thirty-one-bed, mixed medicosurgical department of intensive care.
Patients: All adult patients with a serum albumin concentration =30 g/L were assessed for eligibility. Principal exclusion criteria were expected length of stay <72 hrs, life expectancy <3 months or a do-not-resuscitate order, albumin administration in the preceding 24 hrs, or evidence of fluid overload.
Interventions: The 100 patients were randomized to receive 300 mL of 20% albumin solution on the first day, then 200 mL/day provided their serum albumin concentration was <31 g/dL (albumin group), or to receive no albumin (control group).
Measurements and Main Results: The primary outcome was the effect of albumin administration on organ function as assessed by a delta Sequential Organ Failure Assessment score from day 1 to day 7 (or the day of intensive care discharge or death, whichever came first). The two groups of 50 patients were comparable at baseline for age, gender, albumin concentration, and Acute Physiology and Chronic Health Evaluation II score. Albumin concentration did not change over time in the control group but increased consistently in the albumin group (p < .001). Organ function improved more in the albumin than in the control group (p = .026), mainly due to a difference in respiratory, cardiovascular, and central nervous system components of the Sequential Organ Failure Assessment score. Diuretic use was identical in both groups, but mean fluid gain was almost three times higher in the control group (1679 ± 1156 vs. 658 ± 1101 mL, p = .04). Median daily calorie intake was higher in the albumin than in the control group (1122 [935-1158] vs. 760 [571-1077] kcal, p = .05).
Conclusions: Albumin administration may improve organ function in hypoalbuminemic critically ill patients. It results in a less positive fluid balance and a better tolerance to enteral feeding.
Introduction
Hypoalbuminemia occurs commonly in the intensive care unit (ICU) and may be due to decreased synthesis by the liver and/or to increased losses, either internally (in the interstitium as a result of increased capillary permeability) or externally (through blood losses or exudates or increased proteolysis and clearance). The administration of albumin solutions to correct hypoalbuminemia has been debated over the years as it is not clear if hypoalbuminemia is simply a marker of the severity of disease or is causally linked to the development of complications. Moreover, albumin administration may have deleterious effects including altered coagulation, altered renal function, decreased myocardial contractility, immunosuppression, and worsened edema due to the passage of albumin into the interstitial compartment.
The now famous Cochrane meta-analysis of clinical trials addressing albumin administration in the critically ill indicated that the relative risk of death after albumin administration was 1.68 (95% confidence interval 1.26-2.23) in all patients and 1.69 (1.07-2.67) in hypoalbuminemic patients. A more recent meta-analysis on albumin administration showed no increased mortality rate in patients regardless of the indication for receiving it, although a recent observational study of 3,147 acutely ill patients reported that albumin administration was independently associated with a lower 30-day survival, using a Cox proportional hazard model, and that, in 339 pairs matched according to a propensity score, ICU and hospital mortality rates were higher in patients who received albumin than in those who did not. However, the Saline vs. Albumin Fluid Evaluation (SAFE) study, an Australian randomized controlled trial that recruited >7,000 patients, showed no differences in outcome between patients treated with 4% albumin as their resuscitation fluid and those receiving saline.
The question of whether to administer albumin in hypoalbuminemic patients, however, remains largely unanswered. It is difficult to imagine how hypoalbuminemia could be beneficial. For example, hypoproteinemia has been shown to correlate with the development of acute respiratory distress syndrome and other complications, and hypoalbuminemia has been associated with worse outcomes from cardiac surgery. Indeed, a meta-analysis of 90 cohort studies and nine prospective controlled studies showed that hypoalbuminemia was an independent predictor of poor outcome. This association between hypoalbuminemia and poor outcome appeared to be independent of both nutritional status and inflammation. Analysis of serum albumin concentration in the controlled trials of albumin therapy suggested that complication rates may be reduced when the serum albumin concentration reached during albumin administration exceeds 30 g/L. Also of concern is that mortality, the usual end point of these trials, may be insensitive in a critical care setting, and many have argued that morbidity may be a more sensitive end point. In a recent multiple-center trial, 40 mechanically ventilated patients with acute lung injury or acute respiratory distress syndrome who had total protein concentrations <6.0 g/dL were randomized to receive furosemide with placebo or furosemide with albumin for 72 hrs. Patients who received albumin had improved oxygenation, with greater net negative fluid balance and better maintenance of hemodynamic stability.
In this pilot study, we used the concept of delta Sequential Organ Failure Assessment (SOFA), recently also used to assess effects of activated protein C on organ function in patients of the PROWESS study, to assess the effects of albumin therapy on morbidity, and we prospectively tested the hypothesis that administration of albumin to correct hypoalbuminemia might have beneficial effects on organ function in a mixed population of critically ill patients.
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