D. Jamie Cooper

Predicting survival after ECMO for refractory cardiogenic shock: the survival after veno-arterial-ECMO (SAVE)-score

RATIONALE Extracorporeal membrane oxygenation (ECMO) may provide mechanical pulmonary and circulatory support for patients with cardiogenic shock refractory to conventional medical therapy. Prediction of survival in these patients may assist in management of these patients and comparison of results from different centers. AIMS To identify pre-ECMO factors which predict survival from refractory cardiogenic shock requiring ECMO and create the survival after veno-arterial-ECMO (SAVE)-score. METHODS AND RESULTS Patients with refractory cardiogenic shock treated with veno-arterial ECMO between January 2003 and December 2013 were extracted from the international Extracorporeal Life Support Organization registry. Multivariable logistic regression was performed using bootstrapping methodology with internal and external validation to identify factors independently associated with in-hospital survival. Of 3846 patients with cardiogenic shock treated with ECMO, 1601 (42%) patients were alive at hospital discharge. Chronic renal failure, longer duration of ventilation prior to ECMO initiation, pre-ECMO organ failures, pre-ECMO cardiac arrest, congenital heart disease, lower pulse pressure, and lower serum bicarbonate (HCO3) were risk factors associated with mortality. Younger age, lower weight, acute myocarditis, heart transplant, refractory ventricular tachycardia or fibrillation, higher diastolic blood pressure, and lower peak inspiratory pressure were protective. The SAVE-score (area under the receiver operating characteristics [ROC] curve [AUROC] 0.68 [95%CI 0.64-0.71]) was created. External validation of the SAVE-score in an Australian population of 161 patients showed excellent discrimination with AUROC = 0.90 (95%CI 0.85-0.95). CONCLUSIONS The SAVE-score may be a tool to predict survival for patients receiving ECMO for refractory cardiogenic shock (www.save-score.com).

Mechanical ventilation during extracorporeal membrane oxygenation

The timing of extracorporeal membrane oxygenation (ECMO) initiation and its outcome in the management of respiratory and cardiac failure have received considerable attention, but very little attention has been given to mechanical ventilation during ECMO. Mechanical ventilation settings in non-ECMO studies have been shown to have an effect on survival and may also have contributed to a treatment effect in ECMO trials. Protective lung ventilation strategies established for non-ECMO-supported respiratory failure patients may not be optimal for more severe forms of respiratory failure requiring ECMO support. The influence of positive end-expiratory pressure on the reduction of the left ventricular compliance may be a matter of concern for patients receiving ECMO support for cardiac failure. The objectives of this review were to describe potential mechanisms for lung injury during ECMO for respiratory or cardiac failure, to assess the possible benefits from the use of ultra-protective lung ventilation strategies and to review published guidelines and expert opinions available on mechanical ventilation-specific management of patients requiring ECMO, including mode and ventilator settings. Articles were identified through a detailed search of PubMed, Ovid, Cochrane databases and Google Scholar. Additional references were retrieved from the selected studies. Growing evidence suggests that mechanical ventilation settings are important in ECMO patients to minimize further lung damage and improve outcomes. An ultra-protective ventilation strategy may be optimal for mechanical ventilation during ECMO for respiratory failure. The effects of airway pressure on right and left ventricular afterload should be considered during venoarterial ECMO support of cardiac failure. Future studies are needed to better understand the potential impact of invasive mechanical ventilation modes and settings on outcomes.

Infections Acquired by Adults Who Receive Extracorporeal Membrane Oxygenation: Risk Factors and Outcome

OBJECTIVES To analyze infectious complications that occur in patients who receive extracorporeal membrane oxygenation (ECMO), associated risk factors, and consequences on patient outcome. DESIGN Retrospective observational survey from 2005 through 2011. PARTICIPANTS AND SETTING Patients who required ECMO in an Australian referral center. METHODS Cases of bloodstream infection (BSI), catheter-associated urinary tract infection (CAUTI), and ventilator-associated pneumonia (VAP) that occurred in patients who received ECMO were analyzed. RESULTS A total of 146 ECMO procedures were performed for more than 48 hours in 139 patients, and 36 patients had a total of 46 infections (30.1 infectious episodes per 1,000 days of ECMO). They included 24 cases of BSI, 6 of them secondary to VAP; 23 cases of VAP; and 5 cases of CAUTI. The most frequent pathogens were Enterobacteriaceae (found in 16 of 46 cases), and Candida was the most common cause of BSI (in 9 of 24 cases). The Sequential Organ Failure Assessment score before ECMO initiation and the number of days of support were independently associated with a risk of BSI, with odds ratios of 1.23 (95% confidence interval [CI], 1.03-1.47; [Formula: see text]) and 1.08 (95% CI, 1.03-1.19]; [Formula: see text]), respectively. Infected patients did not have a significantly higher mortality compared with uninfected patients (41.7% vs 32%; [Formula: see text]), but intensive care unit length of stay (16 days [interquartile range, 8-26 days] vs 11 days [IQR, 4-19 days]; [Formula: see text]) and hospital length of stay (33.5 days [interquartile range, 15.5-55.5] vs 24 days [interquartile range, 9-42 days]; [Formula: see text]) were longer. CONCLUSION The probability of infection increased with the duration of support and the severity of illness before initiation of ECMO. Infections affected length of stay but did not have an impact on mortality.

A pilot feasibility trial of allocation of freshest available red blood cells versus standard care in critically ill patients

BACKGROUND: Prolonged storage of red blood cells (RBCs) may increase posttransfusion adverse events in critically ill patients. We aimed to evaluate in intensive care unit (ICU) patients 1) the feasibility of allocating freshest available compatible RBCs versus standard care and 2) the suitability of this approach in the design of a large randomized controlled trial (RCT).

PROphylaxis for ThromboEmbolism in Critical Care Trial protocol and analysis plan.

BACKGROUND This article reports the preparatory studies as well as the design, implementation, and a priori analysis plans of PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) before dissemination of results. PROphylaxis for ThromboEmbolism in Critical Care Trial (NCT00182143) is a randomized, stratified, concealed international trial comparing subcutaneous injection of unfractionated heparin (UFH) 5000 IU or the low-molecular weight heparin (LMWH) dalteparin 5000 IU once daily plus once-daily placebo for the duration of the intensive care unit stay. METHODS The objective of PROTECT is to examine, among medical-surgical critically ill patients, the effect of the LMWH vs heparin on the primary outcome of proximal leg deep vein thrombosis (DVT) and the following secondary outcomes: DVT elsewhere, pulmonary embolism, any venous thromboembolism (DVT or pulmonary embolism), the composite of venous thromboembolism or death, bleeding, and heparin-induced thrombocytopenia. Patients are followed up to death or hospital discharge. Venous thromboembolism events were included after intensive care unit discharge. All patients, families, clinicians, research personnel, and the trial biostatistician are blind to allocation. RESULTS We describe the pilot work, large trial methodology, implementation methods, and the analytic plan. Patient recruitment is complete, but 2 patients remain in the hospital. The rigorous design of PROTECT suggests that the risk of systematic error will be low. The sample size suggests that the risk of random error will be low. PROTECT will be the largest investigator-initiated peer-review funded thromboprophylaxis trial in critical care in the world. CONCLUSIONS If PROTECT shows that LMWH is more effective than UFH, this trial will change practice in that LMWH may be the anticoagulant thromboprophylaxis of choice for this population. If the results show that UFH is as effective or more effective than LMWH, intensivists in many parts of the world may continue to use UFH, whereas those currently using LMWH may reconsider and change to use UFH. Unfavorable consequences such as major bleeding, ease of use, and the costs of complications will also factor into such decisions.

A systematic review and consensus definitions for standardised end-points in perioperative medicine: pulmonary complications

Background: There is a need for robust, clearly defined, patient‐relevant outcome measures for use in randomised trials in perioperative medicine. Our objective was to establish standard outcome measures for postoperative pulmonary complications research. Methods: A systematic literature search was conducted using MEDLINE, Web of Science, SciELO, and the Korean Journal Database. Definitions were extracted from included manuscripts. We then conducted a three‐stage Delphi consensus process to select the optimal outcome measures in terms of methodological quality and overall suitability for perioperative trials. Results: From 2358 records, the full texts of 81 manuscripts were retrieved, of which 45 met the inclusion criteria. We identified three main categories of outcome measure specific to perioperative pulmonary outcomes: (i) composite outcome measures of multiple pulmonary outcomes (27 definitions); (ii) pneumonia (12 definitions); and (iii) respiratory failure (six definitions). These were rated by the group according to suitability for routine use. The majority of definitions were given a low score, and many were imprecise, difficult to apply consistently, or both, in large patient populations. A small number of highly rated definitions were identified as appropriate for widespread use. The group then recommended four outcome measures for future use, including one new definition. Conclusions: A large number of postoperative pulmonary outcome measures have been used, but most are poorly defined. Our four recommended outcome measures include a new definition of postoperative pulmonary complications, incorporating an assessment of severity. These definitions will meet the needs of most clinical effectiveness trials of treatments to improve postoperative pulmonary outcomes.

Systematic review and consensus definitions for standardised endpoints in perioperative medicine: postoperative cancer outcomes

Background The Standardising Endpoints for Perioperative Medicine group was established to derive an appropriate set of endpoints for use in clinical trials related to anaesthesia and perioperative medicine. Anaesthetic or analgesic technique during cancer surgery with curative intent may influence the risk of recurrence or metastasis. However, given the current equipoise in the existing literature, prospective, randomised, controlled trials are necessary to test this hypothesis. As such, a cancer subgroup was formed to derive endpoints related to research in onco‐anaesthesia based on a current evidence base, international consensus and expert guidance. Methods We undertook a systematic review to identify measures of oncological outcome used in the oncological, surgical, and wider literature. A multiround Delphi consensus process that included up to 89 clinician–researchers was then used to refine a recommended list of endpoints. Results We identified 90 studies in a literature search, which were the basis for a preliminary list of nine outcome measures and their definitions. A further two were added during the Delphi process. Response rates for Delphi rounds one, two, and three were 88% (n=9), 82% (n=73), and 100% (n=10), respectively. A final list of 10 defined endpoints was refined and developed, of which six secured approval by ≥70% of the group: cancer health related quality of life, days alive and out of hospital at 90 days, time to tumour progression, disease‐free survival, cancer‐specific survival, and overall survival (and 5‐yr overall survival). Conclusion Standardised endpoints in clinical outcomes studies will support benchmarking and pooling (meta‐analysis) of trials. It is therefore recommended that one or more of these consensus‐derived endpoints should be considered for inclusion in clinical trials evaluating a causal effect of anaesthesia–analgesia technique on oncological outcomes.