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Critical Care Reviews Newsletter

February 17^th 2013

Welcome

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Welcome to the 63rd Critical Care Reviews Newsletter, bringing you the best critical care research published in the past week, plus a wide range of free full text review articles and guidelines from over 300 clinical and scientific journals.

There is little primary research this week, with meta analysis instead dominating this week's research report. However, a small measurement study does question the use of haemglobin and haematocrit values as a means to guide red cell transfusion. Also tedizolid phosphate, a novel oxazolidinone, was shown to be non-inferior to linezolid for the treatment of acute bacterial skin and skin structure infections. There are a couple of study critiques as well as new guidance on the management of subarachnoid haemorrhage.

Amongst the 35 clinical review articles are several from Advances in Chronic Kidney Disease, which provide an excellent update across a range of conditions in critical care. There are a couple of non-clinical review articles also, on negligence and the top journal selectivity index.

The topic for This Week's Papers is Staphlococcal Aureus, starting with a paper on PVL necrotizing pneumonia in tomorrow's Paper of the Day.

Research

Blood Transfusion: Haematocrit as a Transfusion Trigger

Using a non-radioactive double-tracer technique to assess blood volume components in 46 healthy male endurance athletes, Jacob et al demonstrated that red cell volume (2,282±283 mL) did not correlate with either haematocrit (0.42±0.02) or haemoglobin concentration (14.2±0.8, P>0.05), but was predictable from body surface area (red cell volume [mL]=1,547 x body surface area [m²]–723; r=.88, P<0.01). A similar accuracy was unobtainable using any potential predictor for plasma or blood volume, haematocrit or haemoglobin concentration. Red cell volume showed high intra-individual stability when measured again after 4 weeks, whereas plasma volume oscillated in both directions by up to 22%. Conclusion: This small study questions the validity of basing transfusion thresholds on red cell concentrations, rather than blood volumes, although this remains to be tested in a clinically setting.

Full Text: Jacob. Haematocrit is invalid for estimating red cell volume: a prospective study in male volunteers. Blood Transfus 2012;10(4):471–479

British Medical Journal: Hydroxyethyl Starch

Haase et al completed a systematic review and meta analysis in 9 trials and 3456 patients, to assess the effects of fluid therapy with hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin on mortality, kidney injury, bleeding, and serious adverse events in patients with sepsis. Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin did not affect the relative risk of death (1.04, 95% CI 0.89 to 1.22, 3414 patients, eight trials), but in the predefined analysis of trials with low risk of bias the relative risk of death was 1.11 (1.00 to 1.23, trial sequential analysis (TSA) adjusted 95% CI 0.95 to 1.29, 3016 patients, four trials). In the hydroxyethyl starch group, renal replacement therapy was used more (1.36, 1.08 to 1.72, TSA adjusted 1.03 to 1.80, 1311 patients, five trials), and the relative risk of acute kidney injury was 1.18 (0.99 to 1.40, TSA adjusted 0.90 to 1.54, 994 patients, four trials). More patients in the hydroxyethyl starch group were transfused with red blood cells (1.29, 1.13 to 1.48, TSA adjusted 1.10 to 1.51, 973 patients, three trials), and more patients had serious adverse events (1.30, 1.02 to 1.67, TSA adjusted 0.93 to 1.83, 1069 patients, four trials). The transfused volume of red blood cells did not differ between the groups (mean difference 65 mL, 95% CI −20 to 149 mL, three trials). Conclusion: In sepsis, the use of hydroxyethyl starch 130/0.38-0.45, versus crystalloid or albumin, was associated with increased use of renal replacement therapy, increased red cell transfusion, and more serious adverse events.

Full Text: Haase. Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin in patients with sepsis: systematic review with meta-analysis and trial sequential analysis. BMJ 2013;346:f839

Intensive Care Medicine: Hydroxyethyl Starch

Gattas and colleagues undertook a systematic review and meta analysis of 35 trials and 10,391 patients to compare outcomes between acutely ill adults fluid resuscitated with 6 % hydroxyethyl starch (6% HES 130/0.4) or other resuscitation fluids. The mortality rate not-significantly higher (HES:19.8%, 928/4,691 versus control: 18.5%, 871/4,720; relative risk with HES 1.08, 95 % CI: 1.00 to 1.17, I ² = 0 %). Renal replacement therapy occurred more often with HES therapy (HES: 8.9%, 378/4,236 versus control: 7.2%, 306/4,260;; relative risk with HES 1.25, 95 % CI 1.08 to 1.44, I ² = 0 %). Conclusion: Fluid resuscitation with 6% HES 130/0.4 is associated with an increased risk of RRT, and with a strong signal of increaed mortality.

Abstract: Gattas. 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. Intensive Care Med 2013;epublished Febuary 14th

Editorial: Perner. Evidence-based fluid therapy. Intensive Care Medicine 2013;epublished February 14th

PLoS One: N-Acetylcysteine for Contrast-Induced Nephropathy

Sun et al performed a systematic review and meta analysis, comprising 10 studies and 1916 patients, to assess the efficacy of intravenous N-acetylcysteine for preventing contrast-induced nephropathy. NAC was not associated with a reduction in risk ratio for contrast-induced nephropathy (risk ratio 0.68; 95% CI, 0.46 to 1.02). There was evidence of significant heterogeneity in NAC effect across studies (Q = 17.42, P = 0.04; I² = 48%). Meta-regression revealed no significant relation between the relative risk of contrast-induced nephropathy and identified differences in participant or study characteristics. Conclusion: The author's conclude that research on intravenous N-acetylcysteine and the incidence of CIN is too inconsistent at present to warrant a conclusion on efficacy.

Full Text: Sun. Intravenous N-Acetylcysteine for Prevention of Contrast-Induced Nephropathy: A Meta-Analysis of Randomized, Controlled Trials. PLoS ONE 2013;8(1):e55124

Critical Care: ECMO

Zangrillo and colleagues completed a aysytematic review and meta analysis, including 8 studies and 1357 patients, to describe the use of extracorporeal membrane oxygenation (ECMO, n=266, 20%) in severe acute lung injury due to confirmed or suspected H1N1 infection. Patients had a median SOFA score of 9, and had received mechanical ventilation before ECMO implementation for a median of 2 days. ECMO was implanted before inter-hospital patient transfer in 72% of cases and in most patients (94%) the veno-venous configuration was used. ECMO was maintained for a median of 10 days. Outcomes were highly variable among the included studies, with in-hospital or short-term mortality ranging between 8% and 65%, mainly depending on baseline patient features. Random-effect pooled estimates suggested an overall in-hospital mortality of 28% (95% CI 18%-37%; I2=64%).

Full Text: Zangrillo. Extracorporeal membrane oxygenation (ECMO) in patients with H1N1 influenza infection: a systematic review and meta-analysis including 8 studies and 266 patients receiving ECMO. Crit Care. 2013 Feb 13;17(1):R30

Journal of the American Medical Association: Tedizolid - a new gram positive antimicrobial

Prokocimer and colleagues undertook an international phase 3, randomized, double-blind, noninferiority trial in 667 patients with acute bacterial skin and skin structure infections to establish the noninferiority of tedizolid phosphate (200 mg orally once daily for 6 days, n=332) versus linezolid (600mg orally 12 hourly for 10 days, n=335). In intent-to-treat analysis, there was no difference in early clinical treatment response rates: tedizolid 79.5% (95% CI 74.8% to 83.7%) versus linezolid 79.4% (95% CI 74.7% to 83.6%); a treatment difference of 0.1%, (95% CI, −6.1% to 6.2%). The sustained day 11 clinical treatment response rates at the end of treatment were also not different: tedizolid 69.3% (95% CI, 64.0% to 74.2%) versus linezolid 71.9% (95% CI, 66.8% to 76.7%); a treatment difference of −2.6%, 95% CI, −9.6% to 4.2%). Similarly, ther were no differences in investigator-assessed clinical treatment success rates at a posttherapy evaluation visit: tedizolid 85.5% (95% CI, 81.3% to 89.1%) versus linezolid 86.0% (95% CI, 81.8% to 89.5%) (a treatment difference of −0.5%, 95% CI, −5.8% to 4.9%, and were similar for 178 patients with methicillin-resistant Staphylococcus aureus isolated from the primary lesion. Conclusions:. Tedizolid phosphate was not inferior to linezolid for treating acute bacterial skin and skin structure infections.

Abstract: Prokocimer. Tedizolid Phosphate vs Linezolid for Treatment of Acute Bacterial Skin and Skin Structure InfectionsThe ESTABLISH-1 Randomized Trial. JAMA 2013;309(6):559-569