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JPEN. Journal of Parenteral and Enteral... Feb 2019Hypoalbuminemia is associated with inflammation. Despite being addressed repeatedly in the literature, there is still confusion regarding its pathogenesis and clinical... (Review)
Review
Hypoalbuminemia is associated with inflammation. Despite being addressed repeatedly in the literature, there is still confusion regarding its pathogenesis and clinical significance. Inflammation increases capillary permeability and escape of serum albumin, leading to expansion of interstitial space and increasing the distribution volume of albumin. The half-life of albumin has been shown to shorten, decreasing total albumin mass. These 2 factors lead to hypoalbuminemia despite increased fractional synthesis rates in plasma. Hypoalbuminemia, therefore, results from and reflects the inflammatory state, which interferes with adequate responses to events like surgery or chemotherapy, and is associated with poor quality of life and reduced longevity. Increasing or decreasing serum albumin levels are adequate indicators, respectively, of improvement or deterioration of the clinical state. In the interstitium, albumin acts as the main extracellular scavenger, antioxidative agent, and as supplier of amino acids for cell and matrix synthesis. Albumin infusion has not been shown to diminish fluid requirements, infection rates, and mortality in the intensive care unit, which may imply that there is no body deficit or that the quality of albumin "from the shelf" is unsuitable to play scavenging and antioxidative roles. Management of hypoalbuminaemia should be based on correcting the causes of ongoing inflammation rather than infusion of albumin. After the age of 30 years, muscle mass and function slowly decrease, but this loss is accelerated by comorbidity and associated with decreasing serum albumin levels. Nutrition support cannot fully prevent, but slows down, this chain of events, especially when combined with physical exercise.
Topics: Capillary Permeability; Humans; Hypoalbuminemia; Inflammation
PubMed: 30288759
DOI: 10.1002/jpen.1451 -
International Journal of Molecular... Apr 2021Hypoalbuminemia is associated with the acquisition and severity of infectious diseases, and intact innate and adaptive immune responses depend on albumin. Albumin... (Review)
Review
Hypoalbuminemia is associated with the acquisition and severity of infectious diseases, and intact innate and adaptive immune responses depend on albumin. Albumin oxidation and breakdown affect interactions with bioactive lipid mediators that play important roles in antimicrobial defense and repair. There is bio-mechanistic plausibility for a causal link between hypoalbuminemia and increased risks of primary and secondary infections. Serum albumin levels have prognostic value for complications in viral, bacterial and fungal infections, and for infectious complications of non-infective chronic conditions. Hypoalbuminemia predicts the development of healthcare-associated infections, particularly with . In coronavirus disease 2019, hypoalbuminemia correlates with viral load and degree of acute lung injury and organ dysfunction. Non-oncotic properties of albumin affect the pharmacokinetics and pharmacodynamics of antimicrobials. Low serum albumin is associated with inadequate antimicrobial treatment. Infusion of human albumin solution (HAS) supplements endogenous albumin in patients with cirrhosis of the liver and effectively supported antimicrobial therapy in randomized controlled trials (RCTs). Evidence of the beneficial effects of HAS on infections in hypoalbuminemic patients without cirrhosis is largely observational. Prospective RCTs are underway and, if hypotheses are confirmed, could lead to changes in clinical practice for the management of hypoalbuminemic patients with infections or at risk of infectious complications.
Topics: Anti-Infective Agents; Bacteremia; COVID-19; Cross Infection; Humans; Hypoalbuminemia; Immunity, Innate; Prognosis; SARS-CoV-2; Serum Albumin
PubMed: 33925831
DOI: 10.3390/ijms22094496 -
Critical Care (London, England) May 2023Fluid normally exchanges freely between the plasma and interstitial space and is returned primarily via the lymphatic system. This balance can be disturbed by diseases... (Review)
Review
Fluid normally exchanges freely between the plasma and interstitial space and is returned primarily via the lymphatic system. This balance can be disturbed by diseases and medications. In inflammatory disease states, such as sepsis, the return flow of fluid from the interstitial space to the plasma seems to be very slow, which promotes the well-known triad of hypovolemia, hypoalbuminemia, and peripheral edema. Similarly, general anesthesia, for example, even without mechanical ventilation, increases accumulation of infused crystalloid fluid in a slowly equilibrating fraction of the extravascular compartment. Herein, we have combined data from fluid kinetic trials with previously unconnected mechanisms of inflammation, interstitial fluid physiology and lymphatic pathology to synthesize a novel explanation for common and clinically relevant examples of circulatory dysregulation. Experimental studies suggest that two key mechanisms contribute to the combination of hypovolemia, hypoalbuminemia and edema; (1) acute lowering of the interstitial pressure by inflammatory mediators such as TNFα, IL-1β, and IL-6 and, (2) nitric oxide-induced inhibition of intrinsic lymphatic pumping.
Topics: Humans; Hypovolemia; Hypoalbuminemia; Edema; Respiration, Artificial; Crystalloid Solutions
PubMed: 37245039
DOI: 10.1186/s13054-023-04496-5 -
European Journal of Internal Medicine Nov 2023Albumin is the most abundant circulating protein and provides about 70% of the plasma oncotic power. The molecule also carries many other biological functions (binding,... (Review)
Review
Albumin is the most abundant circulating protein and provides about 70% of the plasma oncotic power. The molecule also carries many other biological functions (binding, transport and detoxification of endogenous and exogenous compounds, antioxidation, and modulation of inflammatory and immune responses). Hypoalbuminemia is a frequent finding in many diseases, representing usually only a biomarker of poor prognosis rather than a primary pathophysiological event. Despite that, albumin is prescribed in many conditions based on the assumption that correction of hypoalbuminemia would lead to clinical benefits for the patients. Unfortunately, many of these indications are not supported by scientific evidence (or have been even disproved), so that a large part of albumin use is nowadays still inappropriate. Decompensated cirrhosis is the clinical area where albumin administration has been extensively studied and solid recommendations can be made. Besides prevention and treatment of acute complications, long-term albumin administration in patients with ascites has emerged in the last decade has a potential new disease-modifying treatment. In non-hepatological settings, albumin is widely used for fluid resuscitation in sepsis and critical illnesses, with no clear superiority over crystalloids. In many other conditions, scientific evidence supporting albumin prescription is weak or even absent. Thus, given its high cost and limited availability, action is needed to avoid the use of albumin for inappropriate and futile indications to ensure its availability in those conditions for which albumin has been demonstrated to have a real effectiveness and an advantage for the patient.
Topics: Humans; Hypoalbuminemia; Medical Futility; Albumins; Fluid Therapy; Internal Medicine; Liver Cirrhosis
PubMed: 37423819
DOI: 10.1016/j.ejim.2023.07.003 -
Critical Care (London, England) Jul 2014Albumin solutions have been used worldwide for the treatment of critically ill patients since they became commercially available in the 1940s. However, their use has... (Review)
Review
Albumin solutions have been used worldwide for the treatment of critically ill patients since they became commercially available in the 1940s. However, their use has become the subject of criticism and debate in more recent years. Importantly, all fluid solutions have potential benefits and drawbacks. Large multicenter randomized studies have provided valuable data regarding the safety of albumin solutions, and have begun to clarify which groups of patients are most likely to benefit from their use. However, many questions remain related to where exactly albumin fits within our fluid choices. Here, we briefly summarize some of the physiology and history of albumin use in intensive care before offering some evidence-based guidance for albumin use in critically ill patients.
Topics: Albumins; Brain Injuries; Clinical Trials as Topic; Cost-Benefit Analysis; Critical Care; Critical Illness; Fluid Therapy; History, 20th Century; Humans; Hypoalbuminemia; Resuscitation; Sepsis
PubMed: 25042164
DOI: 10.1186/cc13991 -
Kidney International Sep 2012The mechanism of edema formation in the nephrotic syndrome has long been a source of controversy. In this review, through the construct of Starling's forces, we examine... (Review)
Review
The mechanism of edema formation in the nephrotic syndrome has long been a source of controversy. In this review, through the construct of Starling's forces, we examine the roles of albumin, intravascular volume, and neurohormones on edema formation and highlight the evolving literature on the role of primary sodium absorption in edema formation. We propose that a unifying mechanism of sodium retention is present in the nephrotic syndrome regardless of intravascular volume status and is due to the activation of epithelial sodium channel by serine proteases in the glomerular filtrate of nephrotic patients. Finally, we assert that mechanisms in addition to sodium retention are likely operant in the formation of nephrotic edema.
Topics: Animals; Blood Volume; Capillary Permeability; Edema; Humans; Hydrostatic Pressure; Hypoalbuminemia; Kidney; Models, Biological; Nephrotic Syndrome; Neurotransmitter Agents; Proteinuria; Renin-Angiotensin System; Risk Factors; Serum Albumin; Sodium
PubMed: 22718186
DOI: 10.1038/ki.2012.180 -
Clinical Microbiology and Infection :... Jan 2015The aim of this study was to determine whether ertapenem, being highly protein bound, is less effective than other carbapenems in the presence of hypoalbuminemia. In a...
The aim of this study was to determine whether ertapenem, being highly protein bound, is less effective than other carbapenems in the presence of hypoalbuminemia. In a prospective cohort study, we included adults with clinically and microbiologically documented infections caused by carbapenem-susceptible Enterobacteriaceae who were hospitalized in a tertiary medical center from March 2010 to September 2012. We tested whether hypoalbuminemia (serum albumin <2.5 g/dL) had a larger effect on 30-day mortality in subjects treated with ertapenem compared to those treated with meropenem or imipenem (I/M). Logistic regression analysis was used to identify independent risk factors for death including the carbapenem drug and the interaction between albumin and the carbapenem. Of 279 individual subjects included, 173 were treated with ertapenem and 106 with I/M. The odds ratio (OR) for 30-day mortality with hypoalbuminemia was 4.6 (95% confidence interval (CI) 2.1-10.1) among subjects with ertapenem versus 1.2 (95% CI 0.5-2.70) with I/M (p = 0.02 for difference between groups). In the regression model, the interaction between carbapenem type and albumin levels was significant (p = 0.03); for ertapenem lower albumin levels were associated with increased 30-day mortality (OR 2.45, 95% CI 1.19-5.05), while for I/M the change was not significant (OR 0.67, 95% CI 0.31-1.41). The model suggests that the risk of death for ertapenem-treated subjects quintupled when albumin was 2 g/dL compared to 4 g/dL. Hypoalbuminemia was associated with mortality significantly more among subjects treated with ertapenem compared to subjects treated with I/M. The effectiveness of current dosing schemes of ertapenem in subjects with significant hypoalbuminemia should be revisited.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Ertapenem; Humans; Hypoalbuminemia; Israel; Middle Aged; Prospective Studies; Risk Factors; beta-Lactams
PubMed: 25636928
DOI: 10.1016/j.cmi.2014.08.003 -
Journal of Pharmacological Sciences Apr 2005In patients with hypoalbuminemia, the total serum concentration of valproic acid may offer poor clinical information; however, very few clinical laboratories routinely...
In patients with hypoalbuminemia, the total serum concentration of valproic acid may offer poor clinical information; however, very few clinical laboratories routinely analyze the free concentration of the drug. The aim of this study was to design a procedure to normalize the total concentration of valproic acid according to the level of serum albumin and using previously published free fraction values. In 121 adult patients, with albumin levels of 18 - 41 g/L, the total concentration of valproic acid was normalized using the derived equation: C(N) = alpha(H)C(H)/6.5, where alpha(H) is the free fraction of the drug corresponding to the patient's particular albuminemia and C(H) is the total concentration of valproic acid. The value of 6.5 corresponds to the free fraction of the drug for a serum albumin of 42 g/L (percentile 50 of the reference range). For total concentrations lower than 75 mg/L, the predicted normalized valproic acid concentrations were reasonably concordant with the observed normalized concentrations calculated using the data from a protein-binding study. In a significant number of cases, subtherapeutic concentrations of the drug became therapeutic and even supratherapeutic when corrected according to the albumin levels. Furthermore, cases with therapeutic drug concentrations frequently became supratherapeutic when normalized. The limitations and clinical applications of the proposed formula for normalizing the total concentration of valproic acid are presented. It is concluded that it may be useful for the posological management of hypoalbuminemic patients when the free concentration of the drug is not available, and decisions have to be made based on the total serum concentration.
Topics: Adult; Blood Chemical Analysis; Humans; Hypoalbuminemia; Middle Aged; Protein Binding; Reference Values; Serum Albumin; Valproic Acid
PubMed: 15840952
DOI: 10.1254/jphs.fpe04007x -
International Journal of Molecular... Nov 2022Intravenous administration of crystalloid or colloid solutions is the most common intervention for correcting hypovolemia in intensive care unit patients. In critical... (Review)
Review
Intravenous administration of crystalloid or colloid solutions is the most common intervention for correcting hypovolemia in intensive care unit patients. In critical illness, especially sepsis and severe trauma, vascular wall permeability increases, and trans-endothelial escape of serum albumin, the major oncotic plasma constituent, contributes to the development of hypoalbuminemia and edema formation. The volume effects of intravenous human albumin solution exceed those of crystalloid solutions. If hypoalbuminemia is an effect moderator, the crystalloid-to-albumin ratio of fluid resuscitation volumes is not well characterized. Randomized controlled trials have confirmed that intravenous administration of human albumin solutions for volume resuscitation results in a lower net fluid balance compared with crystalloids, and smaller infusion volumes may be sufficient for hemodynamic stabilization when human albumin solutions are used. This narrative review summarizes the current evidence and conclusions drawn regarding the role of hypoalbuminemia in volume resuscitation. In the 'Saline versus Albumin Fluid Evaluation' study using 4% human albumin solution or saline, the saline-to-albumin ratio of study fluids was significantly higher in patients with baseline serum albumin concentrations of 25 g/L or less as compared to patients with baseline serum albumin concentrations of more than 25 g/L. In patients receiving renal replacement therapy, intravenous administration of 20-25% human albumin solution reduces intradialytic hypotension and improves fluid removal better than saline if serum albumin levels are similarly reduced. These data suggest that hypoalbuminemia acts as an effect moderator in volume resuscitation and plasma expansion with albumin solution. The volume effectiveness of intravenous human albumin solution in resuscitation appears to be greater when the serum albumin levels are low. In clinical situations, serum albumin concentrations per se may inform when and how to include intravenous albumin in fluid resuscitation if large amounts of crystalloids are needed, which requires further studies.
Topics: Humans; Hypoalbuminemia; Isotonic Solutions; Crystalloid Solutions; Infusions, Intravenous; Serum Albumin; Serum Albumin, Human
PubMed: 36430652
DOI: 10.3390/ijms232214175 -
Medicine Feb 2023In malnourished patients with colorectal cancer, hypoalbuminemia is common and was proposed to determine the postoperative outcome of colorectal surgery. Mounting... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In malnourished patients with colorectal cancer, hypoalbuminemia is common and was proposed to determine the postoperative outcome of colorectal surgery. Mounting articles published but have not been evaluated. We aim to assess the predictive value of preoperative hypoalbuminemia in patients undergoing colorectal surgery.
METHODS
We performed a literature search from PubMed, Euro PMC, and Cochrane with the terms serum albumin, hypoalbuminemia, prognosis, outcome, colorectal cancer, and neoplasm. We also hand-searched and included any relevant papers. Hypoalbuminemia is defined as plasma albumin level < 3.5 mg/dL. We restricted the included studies to English language and adults undergoing colectomy, laparotomy, laparoscopy, or abdominoperineal resection. Any types of articles were included, except an abstract-only publication and those that did not report the key exposure or outcome of interest. The key exposures were mortality, hospitalization time, and morbid conditions (thrombosis, surgical site infection, sepsis, and wound events). We pooled the odds ratio from each included literature as effect size. The Newcastle Ottawa scale and GRADE were used to determine the quality of each included study.
RESULTS
Hereof 7 observational studies (236,480 individuals) were included. Our meta-analysis found that preoperative hypoalbuminemia can predict the postoperative outcome in colorectal cancer patients. Individuals with hypoalbuminemia were not associated with 30-day mortality (risk ratio [RR] 2.05 [0.72, 5.86], P = .18, I2 = 99%) but were associated with morbidity (RR 2.28 [1.78, 2.93], P < .00001, I2 = 87.5%), surgical complication (RR 1.69 [1.34, 2.13], P < .00001, I2 = 98%), and hospitalization (RR 2.21 [1.93, 2.52], P < .00001, I2 = 0%). According to newcastle ottawa scale, the included studies are of moderate to sound quality.
CONCLUSIONS
The current systematic review and meta-analysis showed that preoperative hypoalbuminemia was significantly associated with morbidity, length of stay, and surgical complication but not mortality.
Topics: Adult; Humans; Hypoalbuminemia; Prognosis; Malnutrition; Colectomy; Colorectal Neoplasms; Postoperative Complications; Risk Factors
PubMed: 36827017
DOI: 10.1097/MD.0000000000032938