Fluid resuscitation with 6% hydroxyethyl starch (130/0.4) in acutely ill patients: an updated systematic review and meta-analysis.

BACKGROUND: Recent research suggests that 6% hydroxyethyl starch (HES) 130/0.4 is one of the most frequently used resuscitation fluids worldwide. The retraction of studies evaluating its use necessitates a reevaluation of available evidence regarding its safety and efficacy. METHODS: We performed a systematic review and meta-analysis of unretracted randomized controlled trials comparing the effects of 6% HES 130/0.4 with other colloid or crystalloid solutions on mortality, acute kidney injury/failure, and bleeding in acutely ill or perioperative patients. A sensitivity analysis including the data from retracted studies was also conducted. RESULTS: Overall, 36 studies reporting 2149 participants met the inclusion criteria, of which 11 (n = 541) have been retracted. Of the remaining 25 studies, there was a high risk of bias in 17 studies; 19 studies (n = 1246) were conducted in perioperative patients and 6 (n = 362) in critically ill patients. Sixteen studies reported mortality: 104 deaths in 1184 participants. The relative risk of death was 0.95 (95% confidence interval 0.64-1.42, I(2) = 0%, P = 0.73); including the retracted studies added a further 14 deaths and the relative risk was 0.92 (95% confidence interval 0.63-1.34, I(2) = 0%, P = 0.95). The data reporting acute kidney injury, red blood cell transfusion, and bleeding were of insufficient quantity and quality and not amenable to meta-analysis. CONCLUSIONS: Published studies are of poor quality and report too few events to reliably estimate the benefits or risks of administering 6% HES 130/0.4. This same conclusion is reached with or without the retracted studies. Given the widespread use of 6% HES 130/0.4, high-quality trials reporting a large number of events are urgently required.

The role of albumin as a resuscitation fluid for patients with sepsis: a systematic review and meta-analysis.

OBJECTIVE: To assess whether resuscitation with albumin-containing solutions, compared with other fluids, is associated with lower mortality in patients with sepsis. DATA SOURCES: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases, the metaRegister of Controlled Trials, and the Medical Editors Trial Amnesty Register. STUDY SELECTION: Prospective randomized clinical trials of fluid resuscitation with albumin-containing solutions compared with other fluid resuscitation regimens, which included a population or subgroup of participants with sepsis, were included. DATA EXTRACTION: Assessment of the validity of included studies and data extraction were conducted independently by two authors. DATA SYNTHESIS: For the primary analysis, the effect of albumin-containing solutions on all-cause mortality was assessed by using a fixed-effect meta-analysis. RESULTS: Seventeen studies that randomized 1977 participants were included in the meta-analysis. There were eight studies that included only patients with sepsis and nine where patients with sepsis were a subgroup of the study population. There was no evidence of heterogeneity, I² = 0%. The use of albumin for resuscitation of patients with sepsis was associated with a reduction in mortality with the pooled estimate of the odds ratio of 0.82 (95% confidence limits 0.67-1.0, p = .047). CONCLUSIONS: In this meta-analysis, the use of albumin-containing solutions for the resuscitation of patients with sepsis was associated with lower mortality compared with other fluid resuscitation regimens. Until the results of ongoing randomized controlled trials are known, clinicians should consider the use of albumin-containing solutions for the resuscitation of patients with sepsis.

Fluid resuscitation with 6 % hydroxyethyl starch (130/0.4 and 130/0.42) in acutely ill patients: systematic review of effects on mortality and treatment with renal replacement therapy.

PURPOSE: To determine whether fluid resuscitation of acutely ill adults with 6 % hydroxyethyl starch (6 % HES 130) with a molecular weight of 130 kD and a molar substitution ratio of approximately 0.4 (6 % HES 130) compared with other resuscitation fluids results in a difference in the relative risk of death or treatment with renal replacement therapy (RRT). METHODS: Systematic review and meta-analysis of randomized controlled trials comparing intravascular fluids for resuscitation of hospitalised adults that reported mortality or treatment with RRT. The risk of bias was assessed independently by two reviewers and meta-analysis was performed using random effects. RESULTS: Thirty-five trials enrolling 10,391 participants were included. The three largest trials had the lowest risk of bias, were published (or completed) in 2012, and together enrolled 77 % of all participants. Death occurred in 928 of 4,691 patients (19.8 %) in the 6 % HES 130 group versus 871 of 4,720 (18.5 %) in the control fluid groups relative risk (RR) in the 6 % HES 130 group 1.08, 95 % confidence interval (CI) 1.00 to 1.17, I (2) = 0 %). Treatment with RRT occurred in 378 of 4,236 patients (8.9 %) in the 6 % HES 130 group versus 306 of 4,260 (7.2 %) in the control fluid group (RR in the 6 % HES 130 group 1.25, 95 % CI 1.08 to 1.44, I (2) = 0 %). CONCLUSIONS: The quality and quantity of data evaluating 6 % hydroxyethyl starch (130/0.4 and 130/0.42) as a resuscitation fluid has increased in the last 12 months. Patients randomly assigned to resuscitation with 6 %HES 130 are at significantly increased risk of being treated with RRT.

Statistical analysis plan for the Crystalloid Versus Hydroxyethyl Starch Trial (CHEST).

BACKGROUND: The Crystalloid Versus Hydroxyethyl Starch Trial (CHEST) is a 7000-patient, multicentre, randomised controlled trial comparing the effects of 6% hydroxyethyl starch (130/0.4) to normal saline for fluid resuscitation in intensive care patients. The trial design is based on the Saline Versus Albumin Fluid Evaluation (SAFE) study and will be the largest fluid resuscitation trial conducted to date. OBJECTIVE: In accordance with two other trials conducted by the investigators, a predetermined statistical analysis plan (SAP) has been described and made public before completion of patient recruitment and data collection. The SAP will be adhered to for the final data analysis of this trial to avoid analysis bias arising from knowledge of study findings. METHODS: The SAP was designed by the chief investigators and statisticians and approved by the CHEST Management Committee. All authors were blind to treatment allocation and to the unblinded data produced during two interim analyses conducted by the Data Safety and Monitoring Board. The data shells were produced from a previously published protocol. Statistical analyses are described in broad detail. Specifically, information relevant to baseline characteristics and processes of care were defined, and statistically relevant descriptive elements described, with appropriate comparisons between groups. Trial outcomes were selected, categorised into primary, secondary and tertiary outcomes, and appropriate statistical comparisons between groups were planned and described. RESULTS: A standard SAP for CHEST was developed. A trial profile outline and list of mock tables were produced. Descriptions of analyses of baseline characteristics, processes of care, measures of efficacy and outcomes were described. Six prespecified subgroups were defined and statistical comparisons between groups in these subgroups were described. In addition, analyses of tertiary outcomes, including health economic and functional outcome assessment, were described. CONCLUSION: We have developed a predetermined SAP for CHEST. This plan accords with high-quality standards of internal validity to minimise analysis bias.

Corticosteroids to prevent extubation failure: a systematic review and meta-analysis.

PURPOSE: To determine whether corticosteroids reduce the rate of extubation failure in intensive care patients of all age groups. METHODS: Medline, EMBASE, the Cochrane Central Register of Controlled Trials, bibliographies of relevant articles, selected conference abstracts and unpublished trial databases were searched. Randomised clinical trials (RCTs) evaluating corticosteroids for the purpose of preventing extubation failure in mechanically ventilated, critically ill patients of all ages were included. Two authors independently assessed the validity of included studies and extracted data regarding characteristics of the studies and the rates of reintubation and manifestations of laryngeal oedema. RESULTS: Fourteen RCTs including 2,600 participants were included. The mean duration of ventilation prior to attempted extubation ranged from 3 to 21 days. There was a reduction in reintubation with the use of corticosteroids, with a pooled odds ratio (OR) of 0.56 (95% CI; 0.41-0.77, P < 0.0005). The effect of corticosteroids tended to be more pronounced in studies when used at least 12 h prior to attempted extubation (OR 0.41, 95% CI; 0.26-0.64). The results were consistent across neonatal, paediatric and adult populations. There was also a reduction in laryngeal oedema in participants receiving corticosteroids, with a pooled OR of 0.36 (95% CI 0.27-0.49, P < 0.0005). CONCLUSIONS: Corticosteroids reduce laryngeal oedema and importantly reduce the incidence of extubation failure in critically ill patients of all ages.

Enteral nutrition versus glucose-based or lipid-based parenteral nutrition and tight glycaemic control in critically ill patients.

OBJECTIVE: Early administration of nutrition and attention to tight glycaemic control are both associated with improved outcomes in critically ill patients. We hypothesized that blood glucose control would be better achieved in patients receiving enteral rather than parenteral nutrition and, in the latter group, would be better achieved using a "balanced" glucose plus lipid solution than a dextrose-based solution as calorie source. METHODS: We conducted a retrospective interrogation of the intensive care database as part of a clinical audit of a 12-bed mixed medical and surgical ICU in a tertiary referral teaching hospital between September 2003 and March 2004. Patients expected to stay in the ICU for longer than 48 hours were treated according to an intensive insulin therapy protocol. They received enteral nutrition (EN) or, if EN was not tolerated, parenteral nutrition (PN) or combined EN and PN. PN comprised a glucose-based solution (GluPN) during the first 3 months of the study and a balanced glucose plus lipid solution (LipPN) during the second 3 months. RESULTS: 96 patients were treated according to the protocol. Patients receiving PN (n = 26) had significantly longer ICU length of stay and greater daily caloric intake than did those receiving EN (n = 70) during both study periods. Mean blood glucose, percentage of blood glucose measurements within the target range, and daily insulin dose did not differ significantly between patients receiving EN and PN or GluPN and LipPN. CONCLUSION: When used in association with a tight glycaemic control regimen, PN is not associated with poorer glycaemic control in critically ill patients than EN.