Non-oncotic properties of albumin. A multidisciplinary vision about the implications for critically ill patients

Introduction: Effective resuscitation with human albumin solutions is achieved with less fluid than with crystalloid solutions. However, the role of albumin in today’s critical care unit is also linked to its multiple pharmacological effects.

Areas covered: The potential clinical benefits of albumin in select populations of critically ill patients like sepsis seem related to immunomodulatory and anti-inflammatory effects, antibiotic transportation and endothelial stabilization. Albumin transports many drugs used in critically ill patients. Such binding to albumin is frequently lessened in critically ill patients with hypoalbuminemia. These changes could result in sub-optimal treatment. Albumin has immunomodulatory capacity by binding several bacterial products. Albumin also influences vascular integrity, contributing to the maintenance of the normal capillary permeability. Moreover, the albumin molecule encompasses several antioxidant properties, thereby significantly reducing re-oxygenation injury, which is especially important in sepsis. In fact, most studies of albumin administration are a combination of a degree of resuscitation with a degree of maintenance or supplementation of albumin.

Expert commentary: The potential clinical benefits of the use of albumin in selected critically ill patients such as sepsis seem related to its immunomodulatory and anti-inflammatory effects, antioxidant properties, antibiotic transportation and endothelial stabilization. Additional studies are warranted to further elucidate the underlying physiologic and molecular rationale.     

脑出血患者气管切开并发肺部感染的预测研究

目的探讨脑出血患者气管切开并发肺部感染的预测方法及价值。 方法选取亳州市人民医院重症医学科自2018年5月至2020年2月收治的142例脑出血气管切开患者为研究对象,按照脑出血气管切开患者并发肺部感染情况,分为发生组和未发生组。分析脑出血气管切开患者肺部感染危险因素,对比2组患者气管切开术后次日血清白蛋白（Alb）、降钙素原（PCT）及D-二聚体（D-D）水平。采用受试者工作特征（ROC）曲线分析血清Alb、PCT、D-D水平及三者联合预测脑出血气管切开并发肺部感染的价值。 结果本组患者中有33例（23.24%）并发肺部感染,纳入发生组,余109例患者纳入未发生组。发生组脑出血气管切开患者的血清Alb水平[（34.28±7.61）g/L]明显低于未发生组[（48.15±9.27）g/L],PCT[（0.25±0.06）ng/mL]和D-D水平[（253.16±41.27）μg/L]均明显高于未发生组[（0.17±0.05）ng/mL,（168.41±35.24）μg/L],差异均具有统计学意义（P<0.05）。慢性阻塞性肺疾病、吸烟史、低蛋白血症、气管切开距离发病时间≥5 d、气管插管、使用呼吸机、应用广谱抗菌药物、进行颅脑手术、血清Alb<40 g/L、PCT≥0.15 ng/L、D-D≥200 μg/L均是影响出血性气管切开患者肺部感染发生的独立危险因素（P<0.05）,入院GCS评分是其保护因素（OR=0.551,P=0.023）;ROC分析显示,血清Alb、PCT、D-D水平预测脑出血气管切开患者并发肺部感染的最佳截断点分别为36.29 g/L、0.23 ng/mL、228.05 μg/L;血清Alb、PCT及D-D三者联合预测脑出血气管切开患者并发肺部感染的灵敏度、特异度、曲线下面积（AUC）分别为69.70%、97.25%、0.912,特异度和AUC均高于单独预测（P<0.05）,灵敏度与单独预测差异无统计学意义（P>0.05）。 结论脑出血气管切开患者并发肺部感染风险高,且慢性阻塞性肺疾病、吸烟史、低蛋白血症等与血清Alb<40 g/L、PCT≥0.15 ng/L、D-D≥200 μg/L均是其影响因素,血清Alb、PCT、D-D水平联合可用于预测肺部感染。     

Long-term albumin infusion in decompensated cirrhosis: A review of current literature

Decompensated cirrhosis is characterized by chronic inflammation and severe portal hypertension leading to systemic circulatory dysfunction. Albumin infusion has been widely used in decompensated cirrhosis in patients with spontaneous bacterial peritonitis, large-volume paracentesis and hepatorenal syndrome. Emerging data suggest long-term albumin infusion has both oncotic and non-oncotic properties which may improve the clinical outcomes in decompensated cirrhosis patients. We review the current literature on both the established and potential role of albumin, and specifically address the controversies of long-term albumin infusion in decompensated cirrhosis patients.     

Improvement in Central Nervous System Functions During Treatment of Liver Failure with Albumin Dialysis MARS—A Review of Clinical,Biochemical, and Electrophysiological Data

The Molecular Adsorbent Recirculating System (MARS) is a nonbiological liver support method based on the principles of dialysis, filtration, and adsorption. It allows the safe and efficient removal of both albumin-bound and water-soluble toxic metabolites, including ammonia, aromatic amino acids, tryptophan, and related phenolic and indolic products, as well as benzodiazepines. A well-documented effect of the treatment is the improvement of the hemodynamic situation of decompensated chronic patients. Systemic vascular resistance, mean arterial pressure, cerebral blood flow, and cerebral oxygen consumption increased significantly. The degree of hepatic encephalopathy decreased significantly. Increased intracranial pressure could be normalized in both chronic and fulminant liver failure. In three randomized clinical trials significant improvement of survival could be demonstrated. In a model of murine neuronal networks cultured on multi-microelectrode array plates and incubated with plasma from liver failure patients, a normalization of the spike and burst pattern could be observed, if plasma samples from MARS-treated patients before and after treatment were compared. In conclusion, MARS significantly improves central nervous system functions. It can serve as a model for the further investigation of the role of protein-bound substances in hepatic encephalopathy and cerebral hemodynamics.     

Development and in vivo evaluation of chitosan nanoparticles for the oral delivery of albumin

Albumin is used as a plasma expander in critically ill patients and for several other clinical applications mainly via intravenous infusion. Oral administration of albumin can improve patient compliance although limited oral bioavailability of proteins is still a major challenge. Although nanomaterials have been extensively utilized for improving oral delivery of proteins, albumin has been utilized only as either a model drug or as a carrier for drug delivery. In the current study, for the first time, chitosan nanoparticles have been developed and extensively optimized to improve oral bioavailability of albumin as a therapeutic protein. Several characterizations have been performed for the albumin-loaded nanoparticles (e.g. drug encapsulation efficiency, DSC, FTIR, particle size, zeta potential, morphology, release kinetics, and enzymatic stability). Nanosized spherical particles were prepared and demonstrated high stability over three months either in a powdered form or as suspensions. Sustained release of albumin over time and high enzymatic stability as compared to the free albumin were observed. In vivo, higher serum concentrations of albumin in normal rabbits and cirrhotic rats were attained following oral and intraperitoneal administrations of the albumin-loaded nanoparticles as compared to the free albumin. The nanoparticles developed in the current study might provide efficient nanovehicles for oral administration of therapeutic albumin.     

L’hypo-albuminémie contribue-t-elle à l’aggravation de l’insuffisance cardiaque ?

BackgroundHypoalbuminemia has now emerged as a powerful prognosticator in heart failure regardless of age, clinical presentation, left ventricular ejection fraction and usual prognostic markers. Growing evidence is that this prognostic value persists after adjusting for causative factors for hypoalbuminemia such as malnutrition, inflammation and liver dysfunction.ObjectiveTo address the prognostic relevance of hypoalbuminemia in frail elderly patients with well-characterized cardiogenic pulmonary edema at high risk for adverse outcome, beyond causative factors for low serum albumin levels. Serum albumin was measured after clinical stabilization to avoid hypervolemia.ResultsIn all, 67 patients with a mean age of 86 years were included. Hospital mortality was 30%. Patients who died and who survived were similar in age, ejection fraction, BNP concentration, serum creatinine, serum hemoglobin, total bilirubin and prealbumin. Patients who died had lower serum albumin levels (P < 0.001), higher blood urea nitrogen (P = 0.03) and higher C-reactive protein (P = 0.02). In multivariate analysis, serum albumin was the sole independent predictor of hospital death (P < 0.01), after adjusting for malnutrition (prealbumin P = ns), inflammation (C-reactive protein P = ns) and liver dysfunction (total bilirubin P = ns).ConclusionSerum albumin is a powerful prognosticator in frail elderly patients with acute cardiogenic pulmonary edema even after adjusting for main causative factors. These results suggest that hypoalbuminemia may contribute to the worsening of heart failure given the physiological properties of serum albumin that includes antioxidant activity and plasma colloid osmotic pressure action. Further studies are critically needed to address the relevance of prevention and correction of hypoalbuminemia in heart failure.     

血清纤维蛋白原水平及白蛋白/球蛋白比值与直肠癌患者生存预后的关系

目的探讨血清纤维蛋白原水平及白蛋白/球蛋白比值对直肠癌患者生存预后的影响。方法选取我科2010年1月至2013年1月收治的直肠癌患者120例,检测术前患者的血清FIB、AGR水平,根据血清FIB、AGR水平,分为FIB正常组(48例)和FIB高水平组(72例)、AGR正常组(45例)和AGR低水平组(75例);分析术前血清FIB、AGR与直肠癌患者的临床病理学特征关系,判断血清FIB、AGR对直肠癌患者生存预后的影响。结果患者检测术前血清FIB高水平组值6.53±1.28 g/L高于FIB正常组3.12±0.61 g/L,差异具有统计学意义(P<0.05);血清AGR低水平组值1.23±0.08低于AGR正常组值2.12±0.19,差异具有统计学意义(P<0.05)。血清FIB、AGR水平与直肠癌患者的BMI、肿瘤直径、TNM分期和淋巴结转移有关(P<0.05)。单因素分析显示:肿瘤直径>2cm、TNMⅢ期、淋巴结转移、FIB升高和AGR降低是影响直肠癌患者的危险因素(P<0.05);多因素分析显示:淋巴结转移、FIB升高和AGR降低是影响直肠癌患者生存预后的独立危险因素(P<0.05)。结论血清FIB、AGR值正常患者生存预后优于血清FIB升高、AGR降低患者;血清FIB水平升高、AGR水平降低可作为影响直肠癌患者生存率的的独立危险因素。     

Fluid distribution kinetics during cardiopulmonary bypass

OBJECTIVE:

The purpose of this study was to examine the isovolumetric distribution kinetics of crystalloid fluid during cardiopulmonary bypass.

METHODS:

Ten patients undergoing coronary artery bypass grafting participated in this prospective observational study. The blood hemoglobin and the serum albumin and sodium concentrations were measured repeatedly during the distribution of priming solution (Ringer''s acetate 1470 ml and mannitol 15% 200 ml) and initial cardioplegia. The rate of crystalloid fluid distribution was calculated based on 3-min Hb changes. The preoperative blood volume was extrapolated from the marked hemodilution occurring during the onset of cardiopulmonary bypass. Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01115166","term_id":"NCT01115166"}}NCT01115166.

RESULTS:

The distribution half-time of Ringer''s acetate averaged 8 minutes, corresponding to a transcapillary escape rate of 0.38 ml/kg/min. The intravascular albumin mass increased by 5.4% according to mass balance calculations. The preoperative blood volume, as extrapolated from the drop in hemoglobin concentration by 32% (mean) at the beginning of cardiopulmonary bypass, was 0.6-1.2 L less than that estimated by anthropometric methods (p<0.02). The mass balance of sodium indicated a translocation from the intracellular to the extracellular fluid space in 8 of the 10 patients, with a median volume of 236 ml.

CONCLUSIONS:

The distribution half-time of Ringer''s solution during isovolumetric cardiopulmonary bypass was 8 minutes, which is the same as for crystalloid fluid infusions in healthy subjects. The intravascular albumin mass increased. Most patients were hypovolemic prior to the start of anesthesia. Intracellular edema did not occur.     

血清铜,锌,铁及其转运蛋白浓度在体外循环术中的急性时相变化

目的：观察血清铜、锌、铁浓度及其转运蛋白在体外循环术后的变化情况。方法：对体外循环的７名男性和４名女性在手术前后不同时间点抽取血清样品样进行铜、锌、铁及其转运蛋白浓度测定。结果：血清铜、锌、铁浓度在手术初期呈相似变化,即先增加再降低,而后各自呈现不同的应急反应。其中锌和铁的变化有显著性差异,而铜的变化在整个研究时期均无显著性差异（Ｐ〉０．０５）;三种转运蛋白均自手术开始时下降,其中白蛋白和转铁蛋白     

IMA在ACS早期诊断的临床价值

目的探讨缺血修饰白蛋白（IMA）诊断急性冠脉综合征（ACS）的价值。方法测定37倒ACS患者（实验组）和80例体检者（健康对照组）血清IMA浓度。建立IMA诊断ACS的ROC曲线,计算敏感度、特异度、阳性预测值、阴性预测值。结果健康对照组与ACS组间血清IMA浓度有显著差异,差异有统计学意义。IMA诊断ACS的曲线下面积（AZ）为0．866（95％C10．791-0．941）,P〈0．001。cut—off值取80．0U／mL时,灵敏度和特异度分别为81．1％％和72．2％,阳性预测位PPV和阴性预测值NPV分别为61．0％％和89．0％。结论缺血修饰白蛋白（IMA）诊断ACS具有高灵敏度和高阴性预测值的特点;可能在早期诊断心肌缺血及辅助排除ACS上具有较大的价值。