Hyperoncotic Albumin Solution Research Articles

The efficacy, safety and effectiveness of hyperoncotic albumin solutions in patients with sepsis: A systematic review and meta-analysis

The efficacy, safety and effectiveness of hyperoncotic albumin solutions in patients with sepsis: A systematic review and meta-analysis

Use of Albumin as a Resuscitative Fluid in the Intensive Care Unit.

Use of Albumin as a Resuscitative Fluid in the Intensive Care Unit.

Intravenous Albumin for Mitigating Hypotension and Augmenting Ultrafiltration during Kidney Replacement Therapy.

Among its many functions, owing to its oversized effect on colloid oncotic pressure, intravascular albumin helps preserve the effective circulatory volume. Hypoalbuminemia is common in hospitalized patients and is found especially frequently in patients who require KRT either for AKI or as maintenance hemodialysis. In such patients, hypoalbuminemia is strongly associated with morbidity, intradialytic hypotension, and mortality. Intravenous albumin may be administered in an effort to prevent or treat hypotension or to augment fluid removal, but this practice is controversial. Theoretically, intravenous albumin administration might prevent or treat hypotension by promoting plasma refilling in response to ultrafiltration. However, clinical trials have demonstrated that albumin administration is not nearly as effective a volume expander as might be assumed according to its oncotic properties. Although intravenous albumin is generally considered to be safe, it is also very expensive. In addition, there are potential risks to using it to prevent or treat intradialytic hypotension. Some recent studies have suggested that hyperoncotic albumin solutions may precipitate or worsen AKI in patients with sepsis or shock; however, the overall evidence supporting this effect is weak. In this review, we explore the theoretical benefits and risks of using intravenous albumin to mitigate intradialytic hypotension and/or enhance ultrafiltration and summarize the current evidence relating to this practice. This includes studies relevant to its use in patients on maintenance hemodialysis and critically ill patients with AKI who require KRT in the intensive care unit. Despite evidence of its frequent use and high costs, at present, there are minimal data that support the routine use of intravenous albumin during KRT. As such, adequately powered trials to evaluate the efficacy of intravenous albumin in this setting are clearly needed.

The Revised Starling Equation: The Debate of Albumin Versus Crystalloids Continues

Objectives: The purpose of this critical narrative review is to discuss the revised Starling equation for microvascular fluid exchange and the associated implications for intravenous fluid administration. Data Sources: PubMed (1946 to December 2019) and EMBASE (1947 to December 2019) were used, and bibliographies of retrieved articles were searched for additional articles. Study Selection and Data Extraction: Articles pertaining to the revised Starling equation and microvascular fluid exchange. Additionally, prospective human studies involving the disposition and oncotic action of radiolabeled albumin and large randomized trials comparing fluid requirements associated with isotonic crystalloid and albumin administration were included. Data Synthesis: In the revised Starling equation, oncotic forces act across the endothelial cell layer, more specifically between the fluid in the vessel lumen and the protein-sparse subglycocalyx space. The revised Starling equation and radiolabeled investigations of albumin necessitate a reconsideration of conventional views of the plasma-expanding properties of exogenous albumin. Large clinical trials demonstrate that the administration of iso-oncotic or hyper-oncotic albumin solutions in patients undergoing resuscitation does not have the reductions in fluid requirements anticipated from a traditional understanding of the oncotic actions of albumin. Relevance to Patient Care and Clinical Practice: When used as a resuscitation fluid, albumin does not have the degree of plasma expansion or intravascular retention commonly used to justify its use. Conclusions: The principles underlying the revised Starling equation in conjunction with data from radiolabeled studies of albumin and large clinical trials demonstrate that albumin does not have the perceived degree of plasma expansion or duration of intravascular retention beyond crystalloid solutions predicted by the classic Starling equation.

Effects of crystalloid, hyper-oncotic albumin, and iso-oncotic albumin on lung and kidney damage in experimental acute lung injury

BackgroundConflicting data have reported beneficial effects of crystalloids, hyper-oncotic albumin (20%ALB), and iso-oncotic albumin (5%ALB) in critically ill patients. Although hyper-oncotic albumin may minimize lung injury, recent studies have shown that human albumin may lead to kidney damage proportional to albumin concentration. In this context, we compared the effects of Ringer’s lactate (RL), 20%ALB, and 5%ALB, all titrated according to similar hemodynamic goals, on pulmonary function, lung and kidney histology, and molecular biology in experimental acute lung injury (ALI).MethodsMale Wistar rats received Escherichia coli lipopolysaccharide intratracheally (n = 24) to induce ALI. After 24 h, animals were anesthetized and randomly assigned to receive RL, 20%ALB, or 5%ALB (n = 6/group) to maintain hemodynamic stability (distensibility index of inferior vena cava < 25%, mean arterial pressure > 65 mmHg). Rats were then mechanically ventilated for 6 h. Six animals, which received neither ventilation nor fluids (NV), were used for molecular biology analyses.ResultsThe total fluid volume infused was higher in RL compared to 5%ALB and 20%ALB (median [interquartile range], 10.8[8.2–33.2] vs. 4.8[3.6–7.7] and 4.3[3.9–6.6] mL, respectively; p = 0.02 and p = 0.003). B-line counts on lung ultrasound (p < 0.0001 and p = 0.0002) and serum lactate levels (p = 0.01 and p = 0.01) were higher in RL than 5%ALB and 20%ALB. Diffuse alveolar damage score was lower in 5%ALB (10.5[8.5–12]) and 20%ALB (10.5[8.5–14]) than RL (16.5[12.5–20.5]) (p < 0.05 and p = 0.03, respectively), while acute kidney injury score was lower in 5%ALB (9.5[6.5–10]) than 20%ALB (18[15–28.5], p = 0.0006) and RL (16 [15–19], p = 0.04). In lung tissue, mRNA expression of interleukin (IL)-6 was higher in RL (59.1[10.4–129.3]) than in 5%ALB (27.0[7.8–49.7], p = 0.04) or 20%ALB (3.7[7.8–49.7], p = 0.03), and IL-6 protein levels were higher in RL than 5%ALB and 20%ALB (p = 0.026 and p = 0.021, respectively). In kidney tissue, mRNA expression and protein levels of kidney injury molecule (KIM)-1 were lower in 5%ALB than RL and 20%ALB, while nephronectin expression increased (p = 0.01 and p = 0.01), respectively.ConclusionsIn a rat model of ALI, both iso-oncotic and hyper-oncotic albumin solutions were associated with less lung injury compared to Ringer’s lactate. However, hyper-oncotic albumin resulted in greater kidney damage than iso-oncotic albumin. This experimental study is a step towards future clinical designs.

Role of permissive hypotension, hypertonic resuscitation and the global increased permeability syndrome in patients with severe hemorrhage: adjuncts to damage control resuscitation to prevent intra-abdominal hypertension.

Secondary intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are closely related to fluid resuscitation. IAH causes major deterioration of the cardiac function by affecting preload, contractility and afterload. The aim of this review is to discuss the different interactions between IAH, ACS and resuscitation, and to explore a new hypothesis with regard to damage control resuscitation, permissive hypotension and global increased permeability syndrome. Review of the relevant literature via PubMed search. The recognition of the association between the development of ACS and resuscitation urged the need for new approach in traumatic shock management. Over a decade after wide spread application of damage control surgery damage control resuscitation was developed. DCR differs from previous resuscitation approaches by attempting an earlier and more aggressive correction of coagulopathy, as well as metabolic derangements like acidosis and hypothermia, often referred to as the 'deadly triad' or the 'bloody vicious cycle'. Permissive hypotension involves keeping the blood pressure low enough to avoid exacerbating uncontrolled haemorrhage while maintaining perfusion to vital end organs. The potential detrimental mechanisms of early, aggressive crystalloid resuscitation have been described. Limitation of fluid intake by using colloids, hypertonic saline (HTS) or hyperoncotic albumin solutions have been associated with favourable effects. HTS allows not only for rapid restoration of circulating intravascular volume with less administered fluid, but also attenuates post-injury oedema at the microcirculatory level and may improve microvascular perfusion. Capillary leak represents the maladaptive, often excessive, and undesirable loss of fluid and electrolytes with or without protein into the interstitium that generates oedema. The global increased permeability syndrome (GIPS) has been articulated in patients with persistent systemic inflammation failing to curtail transcapillary albumin leakage and resulting in increasingly positive net fluid balances. GIPS may represent a third hit after the initial insult and the ischaemia reperfusion injury. Novel markers like the capillary leak index, extravascular lung water and pulmonary permeability index may help the clinician in guiding appropriate fluid management. Capillary leak is an inflammatory condition with diverse triggers that results from a common pathway that includes ischaemia-reperfusion, toxic oxygen metabolite generation, cell wall and enzyme injury leading to a loss of capillary endothelial barrier function. Fluid overload should be avoided in this setting.

Haemodynamic effects of plasma-expansion with hyperoncotic albumin in cirrhotic patients with renal failure: a prospective interventional study

BackgroundPatients with advanced cirrhosis of the liver typically display circulatory disturbance. Haemodynamic management may be critical for avoiding and treating functional renal failure in such patients. This study investigated the effects of plasma expansion with hyperoncotic albumin solution and the role of static haemodynamic parameters in predicting volume responsiveness in patients with advanced cirrhosis.MethodsPatients with advanced cirrhosis (Child B and C) of the liver receiving albumin substitution because of renal compromise were studied using trans-pulmonary thermodilution. Paired measurements before and after two infusions of 200 ml of 20% albumin per patient were recorded and standard haemodynamic parameters such as central venous pressure (CVP), mean arterial pressure (MAP), systemic vascular resistance index (SVRI), cardiac index (CI) and derived variables were assessed, including global end-diastolic blood volume index (GEDVI), a parameter that reflects central blood volumeResults100 measurements in 50 patients (33 m/17 w; age 56 years (± 8); Child-Pugh-score 12 (± 2), serum creatinine 256 μmol (± 150) were analyzed. Baseline values suggested decreased central blood volumes GEDVI = 675 ml/m2 (± 138) despite CVP within the normal range (11 mmHg (± 5). After infusion, GEDVI, CI and CVP increased (682 ml/m2 (± 128) vs. 744 ml/m2 (± 171), p < 0.001; 4.3 L/min/m2 (± 1.1) vs. 4.7 L/min/m2 (± 1.1), p < 0.001; 12 mmHg (± 6) vs. 14 mmHg (± 6), p < 0.001 respectively) and systemic vascular resistance decreased (1760 dyn s/cm5/m2 (± 1144) vs. 1490 dyn s/cm5/m2 (± 837); p < 0.001). Changes in GEDVI, but not CVP, correlated with changes in CI (r2 = 0.51; p < 0.001). To assess the value of static haemodynamic parameters at baseline in predicting an increase in CI of 10%, receiver-operating-characteristic curves were constructed. The areas under the curve were 0.766 (p < 0.001) for SVRI, 0.723 (p < 0.001) for CI, 0.652 (p = 0.010) for CVP and 0.616 (p = 0.050) for GEDVI.ConclusionIn a substantial proportion of patients with advanced cirrhosis, plasma expansion results in an increase in central blood volume. GEDVI but not CVP behaves as an indicator of cardiac preload, whereas high baseline SVRI is predictive of fluid responsiveness.

Small-volume resuscitation with hyperoncotic albumin: a systematic review of randomized clinical trials

BackgroundSmall-volume resuscitation can rapidly correct hypovolemia. Hyperoncotic albumin solutions, long in clinical use, are suitable for small-volume resuscitation; however, their clinical benefits remain uncertain.MethodsRandomized clinical trials comparing hyperoncotic albumin with a control regimen for volume expansion were sought by multiple methods, including computer searches of bibliographic databases, perusal of reference lists, and manual searching. Major findings were qualitatively summarized. In addition, a quantitative meta-analysis was performed on available survival data.ResultsIn all, 25 randomized clinical trials with a total of 1,485 patients were included. In surgery, hyperoncotic albumin preserved renal function and reduced intestinal edema compared with control fluids. In trauma and sepsis, cardiac index and oxygenation were higher after administration of hydroxyethyl starch than hyperoncotic albumin. Improved treatment response and renal function, shorter hospital stay and lower costs of care were reported in patients with liver disease receiving hyperoncotic albumin. Edema and morbidity were decreased in high-risk neonates after hyperoncotic albumin administration. Disability was reduced by therapy with hyperoncotic albumin in brain injury. There was no evidence of deleterious effects attributable to hyperoncotic albumin. Survival was unaffected by hyperoncotic albumin (pooled relative risk, 0.95; 95% confidence interval 0.78 to 1.17).ConclusionIn some clinical indications, randomized trial evidence has suggested certain benefits of hyperoncotic albumin such as reductions in morbidity, renal impairment and edema. However, further clinical trials are needed, particularly in surgery, trauma and sepsis.

Effectiveness of albumin versus normal saline as a test of volume responsiveness in post-cardiac surgery patients

Purpose: A volume challenge is useful for determining whether cardiac output will respond to further volume loading by the Frank-Starling mechanism. To properly test this mechanism, there must be an increase in right atrial pressure (Pra) but this requires variable amounts of normal saline. The purpose of this study was to determine if 100 mL of 25% albumin would reliably provide a predictable increase in Pra and to compare this with a volume challenge with normal saline. As in a previous study, we also examined the potential for the pattern of respiratory variation of Pra to predict the response to a fluid challenge. Materials and Methods: Twenty-eight stable patients following cardiopulmonary bypass surgery were studied in a randomized, nonblinded interventional study in an intensive care unit. All patients had pulmonary artery flotation catheter as part of their routine management and were breathing spontaneously. They were randomized to receive sufficient normal saline to increase Pra by 2 mm Hg (n = 15) or 100 mL of 25% albumin (n = 13). We also tested the ability of the respiratory variation in Pra to predict the response to a fluid challenge. They had to have an inspiratory fall in the pulmonary capillary wedge pressure of more than 2 mm Hg as an indication that they had an adequate inspiratory effort. They were classified as either having or not having an inspiratory fall in Pra. We predicted that patients without an inspiratory fall in Pra should not respond to volume loading. Results: In contrast to our prediction, the increase in Pra with albumin was less than the increase with normal saline. However, the cardiac output increased more with albumin, which suggests that there was an increase in cardiac function with the hypertonic, hyperosmolar albumin solution. In the saline group, a lack of inspiratory fall in Pra successfully predicted that cardiac output would fail to increase with an increase in Pra in 8 out of 10 patients given saline, and 5 of 6 patients given albumin. Conclusion: A hyperoncotic albumin solution appears to have an inotropic effect in patients following cardiopulmonary bypass procedures. We also again show that the pattern of respiratory variation in right atrial pressure is a useful guide to predict response to volume loading.

Whole-body venous capacity and effective total tissue compliance in SHR.

Whole-body venous capacity was examined in conscious 4-month-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive (WKY) rats by determining mean circulatory filling pressure (MCFP) and blood volume. The MCFP was determined in conscious animals after briefly arresting the circulation by inflating an indwelling balloon in the right atrium. Blood volume was determined by dilution of 125I-albumin and 51Cr-red cells. Although blood volume was not significantly different between SHR (60.9 +/- 0.7 ml/kg, SE) and WKY (59.6 +/- 0.8 ml/kg), MCFP was slightly, but significantly elevated in the SHR (9.5 +/- 0.3 vs 8.5 +/- 0.2 mm Hg, mean +/- SE, p less than 0.05). Increased MCFP with normal blood volume suggests decreased venous capacity in the SHR. In addition, effective total tissue compliance (ETTC) was measured in conscious 5-month-old female SHR and WKY. A decrease in tissue fluid volume was induced by i.v. infusion of hyperoncotic albumin solution. Changes in interstitial fluid pressure were monitored continuously with implanted tissue capsules. Changes in tissue fluid volume were estimated from changes in plasma volume and urine volume. In SHR 3 hours postinfusion, tissue fluid volume decreased by 38.7 +/- 2.7 ml/kg and interstitial fluid pressure decreased from -1.4 +/- 0.3 to -6.6 +/- 1.5 mm Hg. In WKY, tissue fluid volume decreased by 32.5 +/- 2.7 ml/kg and interstitial fluid pressure decreased from -1.4 +/- 0.4 to -3.9 +/- 0.5 mm Hg. The linear regression line for delta interstitial fluid pressure and delta fluid volume was estimated for each rat and the inverse of this slope represented ETTC, which averaged 7.4 +/- 1.0 and 9.6 +/- 2.1 ml/kg/mm Hg (p greater than 0.3) in SHR and WKY respectively. Thus, there were no significant differences in interstitial fluid pressure or ETTC between female SHR and WKY. The results of this study confirm a decreased venous capacity in male SHR with established hypertension and provide new information indicating no measurable abnormalities in interstitial fluid pressure or effective total tissue compliance in adult female SHR as compared with WKY.

Effect of increased peritubule protein concentration on proximal tubule reabsorption in the presence and absence of extracellular volume expansion.

The effect of increased peritubule capillary oncotic pressure on sodium reabsorption by the proximal tubule of the dog was investistigated after extracellular volume expansion (ECVE) with Ringer's solution or during continued hydropenia. Control measurements were made after ECVE or during hydropenia and again during renal arterial infusion with hyperoncotic albumin solution. Absolute reabsorption by the proximal tubule was calculated from fractional reabsorption and single nephron filtration rates as determined by micropuncture. Direct measurements of efferent arteriole protein were used to determine efferent arteriolar oncotic pressure. Albumin infused into the renal artery after ECVE significantly increased efferent oncotic pressure by 17.6 plus or minus 5.3 mm Hg. Fractional and absolute reabsorption by the proximal tubule increased from 20 plus or minus 6 to 37 plus or minus 5% and from 22 plus or minus 6 to 36 plus or minus 7 nl/min, respectively. During hydropenia, the albumin infusion significantly increased efferent oncotic pressure by 15.0 plus or minus 4.4 mm Hg. However, in contrast to the effect seen during ECVE, neither fractional nor absolute reabsorption was changed, delta equals 0.3 plus or minus 1.5% and 3 plus or minus 5 nl/min, respectively. Single nephron filtration rates were not significantly different between the groups and were unchanged by the albumin infusion. Peritubule capillary hydrostatic pressures, measured with a null-servo device, were not changed by the albumin infusion in either group. Renal interstitial hydrostatic pressure, measured from chronically implanted polyethylene capsules, was decreased significantly from 7.2 plus or minus 0.9 to 3.4 plus or minus 0.6 mm Hg in the hydropenic group and from 0.6 plus or minus 0.6 to 4.8 plus or minus 0.7 mm Hg in the Ringer's expanded group. In the hydropenic group, the increase in efferent oncotic pressure was nearly compensated for by changes in interstitial forces so that the calculated net force for capillary uptake was almost unchanged, 17.8 mm Hg before vs. 21.4 mm Hg during the albumin infusion. The increased efferent oncotic pressure in the Ringer's expanded group was not compensated, so that the calculated net force for uptake was increased, 11.9 mm Hg before to 22.2 mm Hg during the albumin infusion. Thus, while the increase in efferent oncotic pressure during albumin infusion was not significantly different between the groups, absolute and fractional reabsorptions were increased only in the animals in which the extracellular volume was expanded. The results suggest that ECVE alters the effect of increased peritubule oncotic pressure on sodium reabsorption by the proximal tubule.

Proximal tubule reabsorption after hyperoncotic albumin infusion. Role of parathyroid hormone and dissociation from plasma volume.

Preferential expansion of the plasma volume by infusion of salt-poor hyperoncotic albumin solution decreases sodium reabsorption by the proximal tubule. The present micropuncture studies test the thesis that albumin infusion depresses proximal reabsorption by an effect unrelated to expansion of the plasma volume, perhaps due to an effect of parathyroid hormone (PTH) on proximal sodium reabsorption. Infusion of salt-poor hyperoncotic albumin significantly decreased plasma ionized calcium, increased immunoreactive PTH (iPTH) in plasma, decreased sodium reabsorption by the proximal tubule, and increased phosphate clearance. In contrast, infusions of albumin, in which the ionized calcium was restored to normal plasma levels, had no significant effect on ionized calcium, iPTH, proximal reabsorption, or phosphate clearance in intact dogs. Similarly, in parathyroidectomized animals given a constant replacement infusion of PTH, albumin infusion had no significant effect on proximal reabsorption or phosphate clearance. Plasma volume was markedly expanded following albumin infusion in all groups of dogs. These findings (a) indicate that PTH plays a significant role in the decrease in sodium reabsorption by the renal proximal tubule after salt-poor hyperoncotic albumin infusion, and (b) dissociate preferential expansion of the plasma volume from decreases in sodium reabsorption by the proximal tubule.