David Gattas

Extracorporeal Membrane Oxygenation for 2009 Influenza A(H1N1) Acute Respiratory Distress Syndrome.

CONTEXT The novel influenza A(H1N1) pandemic affected Australia and New Zealand during the 2009 southern hemisphere winter. It caused an epidemic of critical illness and some patients developed severe acute respiratory distress syndrome (ARDS) and were treated with extracorporeal membrane oxygenation (ECMO). OBJECTIVES To describe the characteristics of all patients with 2009 influenza A(H1N1)-associated ARDS treated with ECMO and to report incidence, resource utilization, and patient outcomes. DESIGN, SETTING, AND PATIENTS An observational study of all patients (n = 68) with 2009 influenza A(H1N1)-associated ARDS treated with ECMO in 15 intensive care units (ICUs) in Australia and New Zealand between June 1 and August 31, 2009. MAIN OUTCOME MEASURES Incidence, clinical features, degree of pulmonary dysfunction, technical characteristics, duration of ECMO, complications, and survival. RESULTS Sixty-eight patients with severe influenza-associated ARDS were treated with ECMO, of whom 61 had either confirmed 2009 influenza A(H1N1) (n = 53) or influenza A not subtyped (n = 8), representing an incidence rate of 2.6 ECMO cases per million population. An additional 133 patients with influenza A received mechanical ventilation but no ECMO in the same ICUs. The 68 patients who received ECMO had a median (interquartile range [IQR]) age of 34.4 (26.6-43.1) years and 34 patients (50%) were men. Before ECMO, patients had severe respiratory failure despite advanced mechanical ventilatory support with a median (IQR) Pao(2)/fraction of inspired oxygen (Fio(2)) ratio of 56 (48-63), positive end-expiratory pressure of 18 (15-20) cm H(2)O, and an acute lung injury score of 3.8 (3.5-4.0). The median (IQR) duration of ECMO support was 10 (7-15) days. At the time of reporting, 48 of the 68 patients (71%; 95% confidence interval [CI], 60%-82%) had survived to ICU discharge, of whom 32 had survived to hospital discharge and 16 remained as hospital inpatients. Fourteen patients (21%; 95% CI, 11%-30%) had died and 6 remained in the ICU, 2 of whom were still receiving ECMO. CONCLUSIONS During June to August 2009 in Australia and New Zealand, the ICUs at regional referral centers provided mechanical ventilation for many patients with 2009 influenza A(H1N1)-associated respiratory failure, one-third of whom received ECMO. These ECMO-treated patients were often young adults with severe hypoxemia and had a 21% mortality rate at the end of the study period.

Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care

BACKGROUND The safety and efficacy of hydroxyethyl starch (HES) for fluid resuscitation have not been fully evaluated, and adverse effects of HES on survival and renal function have been reported. METHODS We randomly assigned 7000 patients who had been admitted to an intensive care unit (ICU) in a 1:1 ratio to receive either 6% HES with a molecular weight of 130 kD and a molar substitution ratio of 0.4 (130/0.4, Voluven) in 0.9% sodium chloride or 0.9% sodium chloride (saline) for all fluid resuscitation until ICU discharge, death, or 90 days after randomization. The primary outcome was death within 90 days. Secondary outcomes included acute kidney injury and failure and treatment with renal-replacement therapy. RESULTS A total of 597 of 3315 patients (18.0%) in the HES group and 566 of 3336 (17.0%) in the saline group died (relative risk in the HES group, 1.06; 95% confidence interval [CI], 0.96 to 1.18; P=0.26). There was no significant difference in mortality in six predefined subgroups. Renal-replacement therapy was used in 235 of 3352 patients (7.0%) in the HES group and 196 of 3375 (5.8%) in the saline group (relative risk, 1.21; 95% CI, 1.00 to 1.45; P=0.04). In the HES and saline groups, renal injury occurred in 34.6% and 38.0% of patients, respectively (P=0.005), and renal failure occurred in 10.4% and 9.2% of patients, respectively (P=0.12). HES was associated with significantly more adverse events (5.3% vs. 2.8%, P<0.001). CONCLUSIONS In patients in the ICU, there was no significant difference in 90-day mortality between patients resuscitated with 6% HES (130/0.4) or saline. However, more patients who received resuscitation with HES were treated with renal-replacement therapy. (Funded by the National Health and Medical Research Council of Australia and others; CHEST ClinicalTrials.gov number, NCT00935168.).

Has mortality from acute respiratory distress syndrome decreased over time?: A systematic review.

RATIONALE It is commonly stated that mortality from acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) is decreasing. OBJECTIVES To systematically review the literature assessing ARDS mortality over time and to determine patient- and study-level factors independently associated with mortality. METHODS We searched multiple databases (MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL) for prospective observational studies or randomized controlled trials (RCTs) published during the period 1984 to 2006 that enrolled 50 or more patients with ALI/ARDS and reported mortality. We pooled mortality estimates using random-effects meta-analysis and examined mortality trends before and after 1994 (when a consensus definition of ALI/ARDS was published) and factors associated with mortality using meta-regression models. MEASUREMENTS AND MAIN RESULTS Of 4,966 studies, 89 met inclusion criteria (53 observational, 36 RCTs). There was a total of 18,900 patients (mean age 51.6 years; 39% female). Overall pooled weighted mortality was 44.3% (95% confidence interval [CI], 41.8-46.9). Mortality decreased with time in observational studies conducted before 1994; no temporal associations with mortality were demonstrated in RCTs (any time) or observational studies (after 1994). Pooled mortality from 1994 to 2006 was 44.0% (95% CI, 40.1-47.5) for observational studies, and 36.2% (95% CI, 32.1-40.5) for RCTs. Meta-regression identified study type (observational versus RCT, odds ratio, 1.36; 95% CI, 1.08-1.73) and patient age (odds ratio per additional 10 yr, 1.27; 95% CI, 1.07-1.50) as the only factors associated with mortality. CONCLUSIONS A decrease in ARDS mortality was only seen in observational studies from 1984 to 1993. Mortality did not decrease between 1994 (when a consensus definition was published) and 2006, and is lower in RCTs than observational studies.

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.

A Randomized Controlled Trial of Regional Citrate Versus Regional Heparin Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Adults

Objective:To determine whether regional anticoagulation of continuous renal replacement therapy circuits using citrate and calcium prolongs circuit life and/or affects circulating cytokine levels compared with regional anticoagulation using heparin and protamine. Design:Multicenter, parallel group randomized controlled trial. Setting:Seven ICUs in Australia and New Zealand. Patients:Critically ill adults requiring continuous renal replacement therapy. Interventions:Patients were randomized to receive one of two methods of regional circuit anticoagulation: citrate and calcium or heparin and protamine. Measurements and Main Results:The primary outcome was functional circuit life measured in hours, assessed using repeated events survival analysis. In addition, we measured changes in interleukin-6, interleukin-8, and interleukin-10 blood levels. We randomized 212 subjects who were treated with 857 continuous renal replacement therapy circuits (median 2 circuits per patient [interquartile range, 1–6], 390 in citrate group vs 467 in heparin group). The groups were well matched for baseline characteristics. Patients receiving regional continuous renal replacement therapy anticoagulation with heparin and protamine were more likely to experience circuit clotting than those receiving citrate and calcium (hazard ratio, 2.03 [1.36–3.03]; p < 0.0005; 857 circuits). The median lifespan of the first study circuit in each patient was 39.2 hours (95% CI, 32.1–48.0 hr) in the citrate and calcium group versus 22.8 hours (95% CI, 13.3–34.0 hr) in the heparin and protamine group (log rank p = 0.0037, 204 circuits). Circuit anticoagulation with citrate and calcium had similar effects on cytokine levels compared with heparin and protamine anticoagulation. There were more adverse events in the group assigned to heparin and protamine anticoagulation (11 vs 2; p = 0.011). Conclusions:Regional citrate and calcium anticoagulation prolongs continuous renal replacement therapy circuit life compared with regional heparin and protamine anticoagulation, does not affect cytokine levels, and is associated with fewer adverse events.

Sepsis-induced myocardial depression is associated with transcriptional changes in energy metabolism and contractile related genes: A physiological and gene expression-based approach

Background:Increased nitric oxide production and altered mitochondrial function have been implicated in sepsis-induced cardiac dysfunction. The molecular mechanisms underlying myocardial depression in sepsis and the contribution of nitric oxide in this process however, are incompletely understood. Objectives:To assess the transcriptional profile associated with sepsis-induced myocardial depression in a clinically relevant mouse model, and specifically test the hypothesis that critical transcriptional changes are inducible nitric oxide synthase-dependent. Design:Laboratory investigation. Setting:University affiliated research laboratory. Subjects:C57/BL6 wild type and congenic B6 129P2-Nos2tm1Lau/J (iNOS−/−) mice. Interventions:Assessment of myocardial function after 48 hrs of induction of polymicrobial sepsis by caecal ligation and perforation. Measurements and Results:We compared the myocardial transcriptional profile in C57/BL6 wild type mice and congenic B6 129P2-Nos2tm1Lau/J litter mates after 48 hrs of polymicrobial sepsis induced by caecal ligation and perforation. Profiling of 22,690 expressed sequence tags by gene set enrichment analysis demonstrated that inducible nitric oxide synthase −/− failed to down regulate critical bioenergy and metabolism related genes including the gene for peroxisome proliferator-activated receptor gamma coactivator 1. Bioinformatics analysis identified a striking concordance in down regulation of transcriptional activity of proliferator-activated receptor gamma coactivator 1-related transcription factors resulting in sepsis associated myocardial remodeling as shown by isoform switching in the expression of contractile protein myosin heavy chain. In inducible nitric oxide synthase −/− deficient mice, contractile depression was minimal, and the transcriptional switch was absent. Conclusions:Metabolic and myosin isoform gene expression switch in sepsis-induced myocardial depression is inducible nitric oxide synthase-dependent. Furthermore, we suggest that the molecular switch favoring the expression of fetal isoforms of contraction related proteins is associated with regulation of proliferator-activated receptor gamma coactivator 1 and related transcription factors in an inducible nitric oxide synthase-dependent manner.

Introduction of a new observation chart and education programme is associated with higher rates of vital-sign ascertainment in hospital wards

Introduction Local and national awareness of the need to improve the recognition and response to the clinical deterioration of hospital inpatients is high. The authors designed and implemented a programme to improve recognition of deteriorating patients in their hospital; a new observation chart for vital signs was one of the major elements. The aim of the study is to evaluate the impact of the new chart and associated education programme on the completeness of vital-sign recording in ward areas. Methods The setting is a university-affiliated teaching hospital in Sydney, Australia. Three study periods, each lasting 14 days (preintervention, 2 weeks postintervention, 3 months postintervention), were carried out in three wards. The new observation chart was supported by an education programme. The primary outcome measures were the ascertainment rates of individual vital signs as a proportion of total observation sets. Results Documentation of respiratory rate increased from 47.8% to 97.8% (p<0.001) and was sustained at 3 months postintervention (98.5%). Collection of a full set of vital signs also improved by a similar magnitude. Basic neurological observation for all patients was introduced in the new chart; the uptake of this was very good (93.1%). Ascertainment rates of blood pressure and oxygen saturation also increased by small but significant amounts from good baseline rates of 97% or higher. Conclusion The introduction of a new observation chart, and education regarding its use and importance, was associated with a major improvement in the recording of respiratory rate and other vital signs.

Extracorporeal cardiopulmonary resuscitation for refractory cardiac arrest: A multicentre experience.

AIM To describe the ECPR experience of two Australian ECMO centres, with regards to survival and neurological outcome, their predictors and complications. METHODS Retrospective observational study of prospectively collected data on all patients who underwent extracorporeal cardiopulmonary resuscitation (ECPR) at two academic ECMO referral centres in Sydney, Australia. MEASUREMENTS AND MAIN RESULTS Thirty-seven patients underwent ECPR, 25 (68%) were for in-hospital cardiac arrests. Median age was 54 (IQR 47-58), 27 (73%) were male. Initial rhythm was ventricular fibrillation or pulseless ventricular tachycardia in 20 patients (54%), pulseless electrical activity (n=14, 38%), and asystole (n=3, 8%). 27 (73%) arrests were witnessed and 30 (81%) patients received bystander CPR. Median time from arrest to initiation of ECMO flow was 45min (IQR 30-70), and the median time on ECMO was 3days (IQR 1-6). Angiography was performed in 54% of patients, and 27% required subsequent coronary intervention (stenting or balloon angioplasty 24%). A total of 13 patients (35%) survived to hospital discharge (IHCA 33% vs. OHCA 37%). All survivors were discharged with favourable neurological outcome (Cerebral Performance Category 1 or 2). Pre-ECMO lactate level was predictive of mortality OR 1.35 (1.06-1.73, p=0.016). CONCLUSIONS In selected patients with refractory cardiac arrest, ECPR may provide temporary support as a bridge to intervention or recovery. We report favourable survival and neurological outcomes in one third of patients and pre-ECMO lactate levels predictive of mortality. Further studies are required to determine optimum selection criteria for ECPR.

Current state of the art for renal replacement therapy in critically ill patients with acute kidney injury

Acute kidney injury (AKI) is associated with incremental risk for death and chronic kidney disease and represents a mounting clinical challenge for healthcare professionals. Renal replacement therapy (RRT) use in ICU settings is rising, likely in response to similar trends in AKI, taken together with an ageing population burdened by high prevalence of multi-morbidity and high illness acuity. Numerous features of RRT prescription and delivery are not standardized, nor are they supported from high-quality evidence derived from randomized trials. Despite the publication of rigorous clinical practice guidelines focused on RRT for AKI that are intended to optimize the quality and reliability of RRT in ICU settings, practice patterns and outcomes continue to show significant variability. In this concise review, we aim to summarize new knowledge and recent advances for the provision of RRT for critically ill patients with AKI.

Health‐related quality of life in survivors of acute kidney injury: The Prolonged Outcomes Study of the Randomized Evaluation of Normal versus Augmented Level Replacement Therapy study outcomes

While patients with chronic kidney disease have reduced health‐related quality of life (HRQOL), long‐term HRQOL of survivors of severe acute kidney injury (AKI) remains unclear.