Carol L. Hodgson

Predicting Survival after Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Failure. The Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) Score

RATIONALE Increasing use of extracorporeal membrane oxygenation (ECMO) for acute respiratory failure may increase resource requirements and hospital costs. Better prediction of survival in these patients may improve resource use, allow risk-adjusted comparison of center-specific outcomes, and help clinicians to target patients most likely to benefit from ECMO. OBJECTIVES To create a model for predicting hospital survival at initiation of ECMO for respiratory failure. METHODS Adult patients with severe acute respiratory failure treated by ECMO from 2000 to 2012 were extracted from the Extracorporeal Life Support Organization (ELSO) international registry. Multivariable logistic regression was used to create the Respiratory ECMO Survival Prediction (RESP) score using bootstrapping methodology with internal and external validation. MEASUREMENTS AND MAIN RESULTS Of the 2,355 patients included in the study, 1,338 patients (57%) were discharged alive from hospital. The RESP score was developed using pre-ECMO variables independently associated with hospital survival on logistic regression, which included age, immunocompromised status, duration of mechanical ventilation before ECMO, diagnosis, central nervous system dysfunction, acute associated nonpulmonary infection, neuromuscular blockade agents or nitric oxide use, bicarbonate infusion, cardiac arrest, PaCO2, and peak inspiratory pressure. The receiver operating characteristics curve analysis of the RESP score was c = 0.74 (95% confidence interval, 0.72-0.76). External validation, performed on 140 patients, exhibited excellent discrimination (c = 0.92; 95% confidence interval, 0.89-0.97). CONCLUSIONS The RESP score is a relevant and validated tool to predict survival for patients receiving ECMO for respiratory failure.

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).

Expert consensus and recommendations on safety criteria for active mobilization of mechanically ventilated critically ill adults.

IntroductionThe aim of this study was to develop consensus recommendations on safety parameters for mobilizing adult, mechanically ventilated, intensive care unit (ICU) patients.MethodsA systematic literature review was followed by a meeting of 23 multidisciplinary ICU experts to seek consensus regarding the safe mobilization of mechanically ventilated patients.ResultsSafety considerations were summarized in four categories: respiratory, cardiovascular, neurological and other. Consensus was achieved on all criteria for safe mobilization, with the exception being levels of vasoactive agents. Intubation via an endotracheal tube was not a contraindication to early mobilization and a fraction of inspired oxygen less than 0.6 with a percutaneous oxygen saturation more than 90% and a respiratory rate less than 30 breaths/minute were considered safe criteria for in- and out-of-bed mobilization if there were no other contraindications. At an international meeting, 94 multidisciplinary ICU clinicians concurred with the proposed recommendations.ConclusionConsensus recommendations regarding safety criteria for mobilization of adult, mechanically ventilated patients in the ICU have the potential to guide ICU rehabilitation whilst minimizing the risk of adverse events.

Early mobilization and recovery in mechanically ventilated patients in the ICU: a bi-national, multi-centre, prospective cohort study.

The aim of this study was to investigate current mobilization practice, strength at ICU discharge and functional recovery at 6 months among mechanically ventilated ICU patients. This was a prospective, multi-centre, cohort study conducted in twelve ICUs in Australia and New Zealand. Patients were previously functionally independent and expected to be ventilated for >48 hours. We measured mobilization during invasive ventilation, sedation depth using the Richmond Agitation and Sedation Scale (RASS), co-interventions, duration of mechanical ventilation, ICU-acquired weakness (ICUAW) at ICU discharge, mortality at day 90, and 6-month functional recovery including return to work. We studied 192 patients (mean age 58.1 ± 15.8 years; mean Acute Physiology and Chronic Health Evaluation (APACHE) (IQR) II score, 18.0 (14 to 24)). Mortality at day 90 was 26.6% (51/192). Over 1,351 study days, we collected information during 1,288 planned early mobilization episodes in patients on mechanical ventilation for the first 14 days or until extubation (whichever occurred first). We recorded the highest level of early mobilization. Despite the presence of dedicated physical therapy staff, no mobilization occurred in 1,079 (84%) of these episodes. Where mobilization occurred, the maximum levels of mobilization were exercises in bed (N = 94, 7%), standing at the bed side (N = 11, 0.9%) or walking (N = 26, 2%). On day three, all patients who were mobilized were mechanically ventilated via an endotracheal tube (N = 10), whereas by day five 50% of the patients mobilized were mechanically ventilated via a tracheostomy tube (N = 18). In 94 of the 156 ICU survivors, strength was assessed at ICU discharge and 48 (52%) had ICU-acquired weakness (Medical Research Council Manual Muscle Test Sum Score (MRC-SS) score <48/60). The MRC-SS score was higher in those patients who mobilized while mechanically ventilated (50.0 ± 11.2 versus 42.0 ± 10.8, P = 0.003). Patients who survived to ICU discharge but who had died by day 90 had a mean MRC score of 28.9 ± 13.2 compared with 44.9 ± 11.4 for day-90 survivors (P <0.0001). Early mobilization of patients receiving mechanical ventilation was uncommon. More than 50% of patients discharged from the ICU had developed ICU-acquired weakness, which was associated with death between ICU discharge and day-90. ClinicalTrials.gov NCT01674608. Registered 14 August 2012.

An official American Thoracic Society/European Society of intensive care medicine/society of critical care medicine clinical practice guideline: Mechanical ventilation in adult patients with acute respiratory distress syndrome

Background: This document provides evidence‐based clinical practice guidelines on the use of mechanical ventilation in adult patients with acute respiratory distress syndrome (ARDS). Methods: A multidisciplinary panel conducted systematic reviews and metaanalyses of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations. Results: For all patients with ARDS, the recommendation is strong for mechanical ventilation using lower tidal volumes (4‐8 ml/kg predicted body weight) and lower inspiratory pressures (plateau pressure < 30 cm H2O) (moderate confidence in effect estimates). For patients with severe ARDS, the recommendation is strong for prone positioning for more than 12 h/d (moderate confidence in effect estimates). For patients with moderate or severe ARDS, the recommendation is strong against routine use of high‐frequency oscillatory ventilation (high confidence in effect estimates) and conditional for higher positive end‐expiratory pressure (moderate confidence in effect estimates) and recruitment maneuvers (low confidence in effect estimates). Additional evidence is necessary to make a definitive recommendation for or against the use of extracorporeal membrane oxygenation in patients with severe ARDS. Conclusions: The panel formulated and provided the rationale for recommendations on selected ventilatory interventions for adult patients with ARDS. Clinicians managing patients with ARDS should personalize decisions for their patients, particularly regarding the conditional recommendations in this guideline.

A randomised controlled trial of an open lung strategy with staircase recruitment, titrated PEEP and targeted low airway pressures in patients with acute respiratory distress syndrome

IntroductionTidal volume and plateau pressure minimisation are the standard components of a protective lung ventilation strategy for patients with acute respiratory distress syndrome (ARDS). Open lung strategies, including higher positive end-expiratory pressure (PEEP) and recruitment manoeuvres to date have not proven efficacious. This study examines the effectiveness and safety of a novel open lung strategy, which includes permissive hypercapnia, staircase recruitment manoeuvres (SRM) and low airway pressure with PEEP titration.MethodTwenty ARDS patients were randomised to treatment or ARDSnet control ventilation strategies. The treatment group received SRM with decremental PEEP titration and targeted plateau pressure < 30 cm H2O. Gas exchange and lung compliance were measured daily for 7 days and plasma cytokines in the first 24 hours and on days 1, 3, 5 and 7 (mean ± SE). Duration of ventilation, ICU stay and hospital stay (median and interquartile range) and hospital survival were determined.ResultsThere were significant overall differences between groups when considering plasma IL-8 and TNF-α. For plasma IL-8, the control group was 41% higher than the treatment group over the seven-day period (ratio 1.41 (1.11 to 1.79), P = 0.01), while for TNF-α the control group was 20% higher over the seven-day period (ratio 1.20 (1.01 to 1.42) P = 0.05). PaO2/FIO2 (204 ± 9 versus 165 ± 9 mmHg, P = 0.005) and static lung compliance (49.1 ± 2.9 versus 33.7 ± 2.7 mls/cm H2O, P < 0.001) were higher in the treatment group than the control group over seven days. There was no difference in duration of ventilation (180 (87 to 298) versus 341 (131 to 351) hrs, P = 0.13), duration of ICU stay (9.9 (5.6 to 14.8) versus 16.0 (8.1 to 19.3) days, P = 0.19) and duration of hospital stay (17.9 (13.7 to 34.5) versus 24.7 (20.5 to 39.8) days, P = 0.16) between the treatment and control groups.ConclusionsThis open lung strategy was associated with greater amelioration in some systemic cytokines, improved oxygenation and lung compliance over seven days. A larger trial powered to examine clinically-meaningful outcomes is warranted.Trial registrationACTRN12607000465459

Long-term quality of life in patients with acute respiratory distress syndrome requiring extracorporeal membrane oxygenation for refractory hypoxaemia

IntroductionThe purpose of the study was to assess the long term outcome and quality of life of patients with acute respiratory distress syndrome (ARDS) receiving extracorporeal membrane oxygenation (ECMO) for refractory hypoxemia.MethodsA retrospective observational study with prospective health related quality of life (HRQoL) assessment was conducted in ARDS patients who had ECMO as a rescue therapy for reversible refractory hypoxemia from January 2009 until April 2011 in a tertiary Australian centre. Survival and long-term quality of life assessment, using the Short-Form 36 (SF-36) and the EuroQol health related quality of life questionnaire (EQ5D) were assessed and compared to international data from other research groups.ResultsTwenty-one patients (mean age 36.3 years) with ARDS receiving ECMO for refractory hypoxemia were studied. Eighteen (86%) patients were retrieved from external intensive care units (ICUs) by a dedicated ECMO retrieval team. Eleven (55%) had H1N1 influenza A-associated pneumonitis. Eighteen (86%) patients survived to hospital discharge. Of the 18 survivors, ten (56%) were discharged to other hospitals and 8 (44%) were discharged directly home. Sequelae and health related quality of life were evaluated for 15 of the 18 (71%) long-term survivors (assessment at median 8 months). Mean SF-36 scores were significantly lower across all domains compared to age and sex matched Australian norms. Mean SF-36 scores were lower (minimum important difference at least 5 points) than previously described ARDS survivors in the domains of general health, mental health, vitality and social function. One patient had long-term disability as a result of ICU acquired weakness. Only 26% of survivors had returned to previous work levels at the time of follow-up.ConclusionsThis ARDS cohort had a high survival rate (86%) after use of ECMO support for reversible refractory hypoxemia. Long term survivors had similar physical health but decreased mental health, general health, vitality and social function compared to other ARDS survivors and an unexpectedly poor return to work.

A survey of manual hyperinflation in Australian hospitals.

A telephone survey was conducted to examine the use of manual hyperinflation (MHI) by physiotherapists in intensive care units (ICUs) in 32 Australian teaching hospitals. A 100 per cent response rate was obtained from senior ICU physiotherapists. Results showed that 91 per cent of respondents used manual hyperinflation as a physiotherapy treatment technique. There was strong agreement on the components of the technique, preferred treatment position, contraindications and perceived benefits but considerable variation in duration of treatment, number of breaths per set and circuits used. Fewer than 55 per cent stated that a maximum airways pressure of 40 cm H2O or less was used with MHI and only 31 per cent monitored airways pressure. These results are compared with previously published surveys.

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.

Mechanical Ventilation Management During Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: A Retrospective International Multicenter Study*

Objective:To describe mechanical ventilation settings in adult patients treated for an acute respiratory distress syndrome with extracorporeal membrane oxygenation and assess the potential impact of mechanical ventilation settings on ICU mortality. Design:Retrospective observational study. Setting:Three international high-volume extracorporeal membrane oxygenation centers. Patients:A total of 168 patients treated with extracorporeal membrane oxygenation for severe acute respiratory distress syndrome from January 2007 to January 2013. Interventions:We analyzed the association between mechanical ventilation settings (i.e. plateau pressure, tidal volume, and positive end-expiratory pressure) on ICU mortality using multivariable logistic regression model and Cox-proportional hazards model. Measurement and Main Results:We obtained detailed demographic, clinical, daily mechanical ventilation settings and ICU outcome data. One hundred sixty-eight patients (41 ± 14 years old; PaO2/FIO2 67 ± 19 mm Hg) fulfilled our inclusion criteria. Median duration of extracorporeal membrane oxygenation and ICU stay were 10 days (6–18 d) and 28 days (16–42 d), respectively. Lower positive end-expiratory pressure levels and significantly lower plateau pressures during extracorporeal membrane oxygenation were used in the French center than in both Australian centers (23.9 ± 1.4 vs 27.6 ± 3.7 and 27.8 ± 3.6; p < 0.0001). Overall ICU mortality was 29%. Lower positive end-expiratory pressure levels (until day 7) and lower delivered tidal volume after 3 days on extracorporeal membrane oxygenation were associated with significantly higher mortality (p < 0.05). In multivariate analysis, higher positive end-expiratory pressure levels during the first 3 days of extracorporeal membrane oxygenation support were associated with lower mortality (odds ratio, 0.75; 95% CI, 0.64–0.88; p = 0.0006). Other independent predictors of ICU mortality included time between ICU admission and extracorporeal membrane oxygenation initiation, plateau pressure greater than 30 cm H2O before extracorporeal membrane oxygenation initiation, and lactate level on day 3 of extracorporeal membrane oxygenation support. Conclusions:Protective mechanical ventilation strategies were routinely used in high-volume extracorporeal membrane oxygenation centers. However, higher positive end-expiratory pressure levels during the first 3 days on extracorporeal membrane oxygenation support were independently associated with improved survival. Further prospective trials on the optimal mechanical ventilation strategy during extracorporeal membrane oxygenation support are warranted.