Albumin in Burn Shock Resuscitation: A Meta-Analysis of Controlled Clinical Studies.

Critical appraisal of outcomes after burn shock resuscitation with albumin has previously been restricted to small relatively old randomized trials, some with high risk of bias. Extensive recent data from nonrandomized studies assessing the use of albumin can potentially reduce bias and add precision. The objective of this meta-analysis was to determine the effect of burn shock resuscitation with albumin on mortality and morbidity in adult patients. Randomized and nonrandomized controlled clinical studies evaluating mortality and morbidity in adult patients receiving albumin for burn shock resuscitation were identified by multiple methods, including computer database searches and examination of journal contents and reference lists. Extracted data were quantitatively combined by random-effects meta-analysis. Four randomized and four nonrandomized studies with 688 total adult patients were included. Treatment effects did not differ significantly between the included randomized and nonrandomized studies. Albumin infusion during the first 24 hours showed no significant overall effect on mortality. However, significant statistical heterogeneity was present, which could be abolished by excluding two studies at high risk of bias. After those exclusions, albumin infusion was associated with reduced mortality. The pooled odds ratio was 0.34 with a 95% confidence interval of 0.19 to 0.58 (P < .001). Albumin administration was also accompanied by decreased occurrence of compartment syndrome (pooled odds ratio, 0.19; 95% confidence interval, 0.07-0.50; P < .001). This meta-analysis suggests that albumin can improve outcomes of burn shock resuscitation. However, the scope and quality of current evidence are limited, and additional trials are needed.

Albumin treatment regimen for type 1 hepatorenal syndrome: a dose-response meta-analysis.

BACKGROUND: Recommended treatment for type 1 hepatorenal syndrome consists of albumin and vasoconstrictor. The optimal albumin dose remains poorly characterized. This meta-analysis aimed to determine the impact of albumin dose on treatment outcomes. METHODS: Clinical studies of type 1 hepatorenal syndrome treatment with albumin and vasoconstrictor were sought. Search terms included: hepatorenal syndrome; albumin; vasoconstrictor; terlipressin; midodrine; octreotide; noradrenaline; and norepinephrine. A meta-analysis was performed of hepatorenal syndrome reversal and survival in relation to albumin dose. RESULTS: Nineteen clinical studies with 574 total patients were included, comprising 8 randomized controlled trials, 8 prospective studies and 3 retrospective studies. The pooled percentage of patients achieving hepatorenal syndrome reversal was 49.5% (95% confidence interval, 40.0-59.1%). Increments of 100 g in cumulative albumin dose were accompanied by significantly increased survival (hazard ratio, 1.15; 95% confidence interval, 1.02-1.31; p = 0.023). A non-significant increase of similar magnitude in hepatorenal syndrome reversal was also observed (odds ratio, 1.15; 95% confidence interval, 0.97-1.37; p = 0.10). Expected survival rates at 30 days among patients receiving cumulative albumin doses of 200, 400 and 600 g were 43.2% (95% confidence interval, 36.4-51.3%), 51.4% (95% confidence interval, 46.3-57.1%) and 59.0% (95% confidence interval, 51.9-67.2), respectively. Neither survival nor hepatorenal syndrome reversal was significantly affected by vasoconstrictor dose or type, treatment duration, age, baseline serum creatinine, bilirubin or albumin, baseline mean arterial pressure, or study design, size or time period. CONCLUSIONS: This meta-analysis suggests a dose-response relationship between infused albumin and survival in patients with type 1 hepatorenal syndrome. The meta-analysis provides the best current evidence on the potential role of albumin dose selection in improving outcomes of treatment for type 1 HRS and furnishes guidance for the design of future dose-ranging studies.

Home-made explosive found inside injured Afghan.

There is extensive literature on metal fragments from improvised explosive devices being embedded in patients but there are no reports describing the clinical and radiological appearances of embedded home-made explosive (HME). We present a case of partially detonated HME being found inside a patient's forearm. We discuss the medical management of the injury, the ongoing risk to the patient and surgical team associated with the explosive and the safe disposal of the substance.

Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis: a meta-analysis of randomized trials.

BACKGROUND & AIMS: Renal impairment increases mortality among patients with spontaneous bacterial peritonitis (SBP), despite administration of non-nephrotoxic antibiotics. Albumin infusion has been reported to reduce renal impairment and mortality in patients with SBP. We performed a meta-analysis of randomized controlled trials (RCTs) to quantify the effect of albumin infusion on renal impairment and mortality in patients with SBP. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov for RCTs that evaluated albumin treatment for patients with SBP; we also performed searches by additional methods. Four trials of 288 total patients were included in our analysis. Data were quantitatively combined under a fixed-effects model. RESULTS: We found no evidence of statistically significant heterogeneity or publication bias among the studies analyzed. Albumin was compared with no albumin in 3 trials and with artificial colloid in 1 trial. All patients received antibiotics. The incidence of renal impairment in control groups was 44 of 144 (30.6%), compared with 12 of 144 (8.3%) in groups given albumin. The pooled odds ratio for a reduction in renal impairment after albumin infusion was 0.21 (95% confidence interval, 0.11-0.42). Odds ratios for renal impairment after albumin therapy ranged from 0.19-0.30 among the individual studies. Mortality among controls was 51 of 144 (35.4%), compared with 23 of 144 (16.0%) among patients who received albumin. The pooled odds ratio for decreased mortality after infusion of albumin was 0.34 (95% confidence interval, 0.19-0.60). Odds ratios for mortality in individual RCTs ranged from 0.16-0.55. CONCLUSIONS: In a meta-analysis of 4 RCTs (288 patients), albumin infusion prevented renal impairment and reduced mortality among patients with SBP.

Effect of hydroxyethyl starch on bleeding after cardiopulmonary bypass: a meta-analysis of randomized trials.

OBJECTIVE: The effects of hydroxyethyl starch on bleeding after cardiopulmonary bypass were determined. METHODS: A meta-analysis was performed of postoperative blood loss in randomized clinical trials of hydroxyethyl starch versus albumin for fluid management in adult cardiopulmonary bypass surgery. Impacts of hydroxyethyl starch molecular weight and molar substitution were assessed. Randomized trials directly comparing different hydroxyethyl starch solutions were also included. RESULTS: Eighteen trials with 970 total patients were included. Compared with albumin, hydroxyethyl starch increased postoperative blood loss by 33.3% of a pooled SD (95% confidence interval, 18.2%-48.3%; P < .001). Risk of reoperation for bleeding was more than doubled by hydroxyethyl starch (relative risk, 2.24; 95% confidence interval, 1.14-4.40; P = .020). Hydroxyethyl starch increased transfusion of red blood cells by 28.4% of a pooled SD (95% confidence interval, 12.2%-44.6%; P < .001), of fresh-frozen plasma by 30.6% (95% confidence interval, 8.0%-53.1%; P = .008), and of platelets by 29.8% (95% confidence interval, 3.4%-56.2%; P = .027). None of these effects differed significantly between hydroxyethyl starch 450/0.7 and 200/0.5. Insufficient data were available for hydroxyethyl starch 130/0.4 versus albumin; however, no significant differences were detected in head-to-head comparisons of hydroxyethyl starch 130/0.4 with 200/0.5. Albumin improved hemodynamics. There were no differences in fluid balance, ventilator time, intensive care unit stay, or mortality. CONCLUSIONS: Hydroxyethyl starch increased blood loss, reoperation for bleeding, and blood product transfusion after cardiopulmonary bypass. There was no evidence that these risks could be mitigated by lower molecular weight and substitution.

Albumin infusion in patients undergoing large-volume paracentesis: a meta-analysis of randomized trials.

UNLABELLED: Albumin infusion reduces the incidence of postparacentesis circulatory dysfunction among patients with cirrhosis and tense ascites, as compared with no treatment. Treatment alternatives to albumin, such as artificial colloids and vasoconstrictors, have been widely investigated. The aim of this meta-analysis was to determine whether morbidity and mortality differ between patients receiving albumin versus alternative treatments. The meta-analysis included randomized trials evaluating albumin infusion in patients with tense ascites. Primary endpoints were postparacentesis circulatory dysfunction, hyponatremia, and mortality. Eligible trials were sought by multiple methods, including computer searches of bibliographic and abstract databases and the Cochrane Library. Results were quantitatively combined under a fixed-effects model. Seventeen trials with 1,225 total patients were included. There was no evidence of heterogeneity or publication bias. Compared with alternative treatments, albumin reduced the incidence of postparacentesis circulatory dysfunction (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.27-0.55). Significant reductions in that complication by albumin were also shown in subgroup analyses versus each of the other volume expanders tested (e.g., dextran, gelatin, hydroxyethyl starch, and hypertonic saline). The occurrence of hyponatremia was also decreased by albumin, compared with alternative treatments (OR, 0.58; 95% CI, 0.39-0.87). In addition, mortality was lower in patients receiving albumin than alternative treatments (OR, 0.64; 95% CI, 0.41-0.98). CONCLUSIONS: This meta-analysis provides evidence that albumin reduces morbidity and mortality among patients with tense ascites undergoing large-volume paracentesis, as compared with alternative treatments investigated thus far.

Update on the comparative safety of colloids: a systematic review of clinical studies.

OBJECTIVE: To provide an updated systematic review on the comparative safety of colloids based on recent clinical studies. BACKGROUND: Recent investigations, including large-scale randomized trials and meta-analyses, have sought to determine the effects of colloids on mortality and morbidity. Hypothesized differences in safety profile between hydroxyethyl starch (HES) solutions have also been evaluated in randomized trials. METHODS: Clinical studies reported since 2002 with safety data for acutely ill patients receiving HES, gelatin, dextran, or albumin were sought by computer searches and other methods. Safety endpoints included mortality, morbidity, bleeding and impaired coagulation, and acute kidney injury (AKI). Data extracted from the included study reports were qualitatively summarized. RESULTS: Sixty-nine clinical studies were included. Of those, 42 were randomized controlled trials (RCTs) with 10,382 total patients. New safety data, since 2002, predominantly concerned albumin or HES. A large RCT of intensive care unit patients showed that albumin does not adversely affect survival. Acute kidney injury and a dose-dependent increase in mortality were observed in a large RCT of patients with severe sepsis or septic shock receiving HES. Impaired coagulation and clinical bleeding were frequently reported after HES infusion, especially in cardiac surgery. In head-to-head randomized comparisons of different HES solutions, observed effects on coagulation and renal function were similar. Gelatin showed less impairment of coagulation than HES. Very few safety data related to dextran were identified. CONCLUSIONS: Albumin displayed a more favorable safety profile than HES. Available evidence does not support the existence of consistent safety differences between HES solutions.

Impact of trough IgG on pneumonia incidence in primary immunodeficiency: A meta-analysis of clinical studies.

Primary immunodeficiency disease (PIDD) associated with hypogammaglobulinemia is typically treated with immunoglobulin replacement therapy. When administered as intravenous immunoglobulin (IVIG), an IgG trough occurs prior to the next replacement dose. While frequently measured, IgG trough levels required to minimize infection risk are not established. To address this question, all available studies evaluating trough IgG and pneumonia incidence in PIDD patients with hypogammaglobulinemia receiving IVIG were quantitatively combined by meta-analysis. Seventeen studies with 676 total patients and 2,127 patient-years of follow-up were included. Pneumonia incidence declined by 27% with each 100mg/dL increment in trough IgG (incidence rate ratio, 0.726; 95% confidence interval, 0.658-0.801). Pneumonia incidence with maintenance of 500 mg/dL IgG trough levels (0.113 cases per patient-year) was 5-fold that with 1000 mg/dL (0.023 cases per patient-year). This meta-analysis provides evidence that pneumonia risk can be progressively reduced by higher trough IgG levels up to at least 1000 mg/dL.

Augmentation therapy for alpha1 antitrypsin deficiency: a meta-analysis.

BACKGROUND: Augmentation with exogenous alpha1-antitrypsin (alpha1-AT) is the only specific therapy for alpha1-AT deficiency. Uncertainty persists concerning its effectiveness. PURPOSE: To test the hypothesis that augmentation therapy in patients with alpha1-AT deficiency slows the decline in FEV1. STUDY SELECTION: Randomized and nonrandomized clinical studies with either parallel-group design or single cohort pre-post design were eligible if they compared augmentation therapy with a control regimen and if long-term (> 1 y) longitudinal FEV1 follow-up data were collected. DATA SYNTHESIS: FEV1 data from five trials with 1509 patients were combined by random effects meta-analysis. The decline in FEV1 was slower by 23% (absolute difference, 13.4 ml/year; CI, 1.5 to 25.3 ml/year) among all patients receiving augmentation therapy. This overall protective effect reflected predominantly the results in the subset of patients with baseline FEV1 30-65% of predicted. In that subset, augmentation was associated with a 26% reduction in rate of FEV1 decline (absolute difference, 17.9 ml/year; CI, 9.6 to 26.1 ml/year). Similar trends amongst patients with baseline FEV1 percent of predicted < 30% or > 65% were not statistically significant. CONCLUSIONS: This meta-analysis supports the conclusion that augmentation can slow lung function decline in patients with AAT deficiency Patients with moderate obstruction are most likely to benefit.

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

BACKGROUND: Small-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. METHODS: Randomized 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. RESULTS: In 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). CONCLUSION: In 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.

Morbidity in hospitalized patients receiving human albumin: a meta-analysis of randomized, controlled trials.

OBJECTIVE: To determine the effect of albumin administration on morbidity in acutely ill hospitalized patients. DATA SOURCE: Computer searches of MEDLINE, EMBASE, and the Cochrane Library; hand searches of journals and Index Medicus; inquiries with investigators and fluid product suppliers; and examination of reference lists. No language or time period restrictions were adopted. STUDY SELECTION: Randomized, controlled trials comparing the administration of albumin with that of crystalloid, no albumin, or lower-dose albumin. DATA EXTRACTION: Two investigators independently extracted data. The primary endpoint for the meta-analysis was morbidity, defined as the incidence of complications, including death. Trial quality was evaluated by blinding, allocation concealment, presence of morbidity as a study endpoint, and individual patient crossover. DATA SYNTHESIS: Seventy-one trials were included in the categories of surgery or trauma, burns, hypoalbuminemia, high-risk neonates, ascites, and other indications. The 3,782 randomized patients in the included trials experienced a total of 3,287 complications, including 515 deaths and 2,772 cardiovascular, gastrointestinal, hepatic, infectious, renal, respiratory, and other complications. Albumin significantly reduced overall morbidity, with a risk ratio of 0.92 (confidence interval [CI], 0.86-0.98). Control group albumin dose significantly affected the incidence of complications (p = .002). In 32 trials with no albumin administered to the control group, the risk ratio was 0.77 (CI, 0.67-0.88) compared with 0.89 (CI, 0.80-1.00) in 20 trials with control patients receiving low-dose albumin and 1.07 (CI, 0.96-1.20) in 19 trials with moderate-dose control group albumin. CONCLUSIONS: Albumin reduces morbidity in acutely ill hospitalized patients. Concomitant administration of albumin in the control group can obscure the effects of albumin on clinical outcome in randomized trials.

Albumin versus crystalloid for pump priming in cardiac surgery: meta-analysis of controlled trials.

OBJECTIVES: To determine the effects of pump priming fluid choice on platelets, fluid balance, and clinical outcomes. DESIGN: Meta-analysis of controlled clinical trials. Primary endpoints were platelet counts, colloid oncotic pressure, on-bypass fluid balance, postoperative weight gain, and colloid usage. SETTING: Cardiac surgery with cardiopulmonary bypass. PATIENTS: Adult and pediatric patients undergoing cardiac surgery, including coronary artery bypass grafting, valve procedures, and correction of congenital cardiac anomalies. INTERVENTIONS: Extracorporeal circuit priming with either albumin or crystalloid. MEASUREMENTS AND RESULTS: The meta-analysis included 21 controlled trials with 1,346 total patients. Albumin prime significantly reduced the on-bypass drop in platelet counts. The pooled weighted mean difference in platelet count drop with albumin versus crystalloid prime was -23.8 x 10(9)/L (confidence interval [CI], -42.8 to -4.7 x 10(9)/L). The colloid oncotic pressure decline was also smaller when albumin rather than crystalloid was used for priming, with a pooled weighted mean difference of -3.6 mm Hg (CI, -4.8 to -2.3 mmHg) during bypass and -2.0 mmHg (CI, -2.9 to -1.1 mmHg) after surgery. Albumin prime correspondingly reduced on-bypass positive fluid balance (-584 mL; CI, -819 to -348 mL) and postoperative weight gain (-1.0 kg; CI, -0.6 to -1.3 kg) compared with crystalloid. Postoperative colloid usage was lower with albumin than crystalloid prime (-612 mL; CI, -983 to -241 mL). CONCLUSIONS: Albumin prime better preserves platelet counts than crystalloid. Albumin also favorably influences colloid oncotic pressure, on-bypass positive fluid balance, postoperative weight gain, and colloid usage. The clinical significance of these observations merits further investigation.

A systematic review of the comparative safety of colloids.

HYPOTHESIS: Safety differences exist among colloids widely used for fluid management in acutely ill patients, as judged according to the comparative incidence of adverse events. DATA SOURCES: Colloid safety data for human subjects were sought, without language or time period restrictions, by means of computer searches of bibliographic and clinical trial databases, hand searches of medical journals and Index Medicus, inquiries with investigators and colloid suppliers, and examination of reference lists. Search terms included "colloids", "morbidity", and "mortality". STUDY SELECTION: Controlled trials, cohort studies, pharmacovigilance studies, and prior meta-analyses were independently selected by 2 unblinded investigators. Of 189 candidate studies, 113 were included, with safety data encompassing 1.54 x 10(6) patients and 1.09 x 10(8) colloid infusions. DATA EXTRACTION: Two unblinded investigators independently extracted data. Study limitations and confounding factors were tabulated. DATA SYNTHESIS: With albumin as the reference colloid, the incidence rate ratio for anaphylactoid reactions was 4.51 (95% confidence interval, 2.06-9.89) after hydroxyethyl starch administration, 2.32 (95% confidence interval, 1.21-4.45) after dextran, and 12.4 (95% confidence interval, 6.40-24.0) after gelatin. Pruritus occurrence was significantly increased by hydroxyethyl starch exposure (odds ratio, 1.78; 95% confidence interval, 1.23-2.58). Artificial colloid administration was consistently associated with coagulopathy and clinical bleeding, most frequently in cardiac surgery patients receiving hydroxyethyl starch. On the basis of large-scale pharmacovigilance study results, albumin infusion resulted in a low rate of both total adverse events (3.1 to 8.6 per 10(5) infusions) and serious adverse events (1.29 per 10(6) infusions). CONCLUSIONS: Significant safety differences exist among colloids. Therefore, conclusions regarding the clinical usefulness of colloids as a fluid class should be formed with caution.