Vincent Pellegrino

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.

Refractory cardiac arrest treated with mechanical CPR, hypothermia, ECMO and early reperfusion (the CHEER trial).

INTRODUCTION Many patients who suffer cardiac arrest do not respond to standard cardiopulmonary resuscitation. There is growing interest in utilizing veno-arterial extracorporeal membrane oxygenation assisted cardiopulmonary resuscitation (E-CPR) in the management of refractory cardiac arrest. We describe our preliminary experiences in establishing an E-CPR program for refractory cardiac arrest in Melbourne, Australia. METHODS The CHEER trial (mechanical CPR, Hypothermia, ECMO and Early Reperfusion) is a single center, prospective, observational study conducted at The Alfred Hospital. The CHEER protocol was developed for selected patients with refractory in-hospital and out-of-hospital cardiac arrest and involves mechanical CPR, rapid intravenous administration of 30 mL/kg of ice-cold saline to induce intra-arrest therapeutic hypothermia, percutaneous cannulation of the femoral artery and vein by two critical care physicians and commencement of veno-arterial ECMO. Subsequently, patients with suspected coronary artery occlusion are transferred to the cardiac catheterization laboratory for coronary angiography. Therapeutic hypothermia (33 °C) is maintained for 24h in the intensive care unit. RESULTS There were 26 patients eligible for the CHEER protocol (11 with OHCA, 15 with IHCA). The median age was 52 (IQR 38-60) years. ECMO was established in 24 (92%), with a median time from collapse until initiation of ECMO of 56 (IQR 40-85) min. Percutaneous coronary intervention was performed on 11 (42%) and pulmonary embolectomy on 1 patient. Return of spontaneous circulation was achieved in 25 (96%) patients. Median duration of ECMO support was 2 (IQR 1-5) days, with 13/24 (54%) of patients successfully weaned from ECMO support. Survival to hospital discharge with full neurological recovery (CPC score 1) occurred in 14/26 (54%) patients. CONCLUSIONS A protocol including E-CPR instituted by critical care physicians for refractory cardiac arrest which includes mechanical CPR, peri-arrest therapeutic hypothermia and ECMO is feasible and associated with a relatively high survival rate.

Extracorporeal membrane oxygenation for respiratory failure in adults

Purpose of reviewThis article reviews case series and trials that evaluated extracorporeal membrane oxygenation (ECMO) for respiratory failure and describes patient and circuit management in the modern era of ECMO support. Recent findingsIn recent years, pivotal progress has been made in the conception and construction of ECMO circuits. They are now simpler, safer, require less anticoagulation and are associated with fewer bleeding complications. The encouraging results of the efficacy and economic assessment of conventional ventilatory support versus ECMO for severe adult respiratory failure (CESAR) trial performed in the United Kingdom and good outcomes of patients who received ECMO as rescue therapy during the recent H1N1 influenza pandemic, in which the latest generation of ECMO technology was used, reignited interest in ECMO for severe acute respiratory distress syndrome (ARDS). SummaryThe latest generation of ECMO systems is more biocompatible, better performing and longer lasting. Although recent studies suggested that veno-venous ECMO might improve the outcomes of patients with ARDS, indications for ECMO use remain uncertain. Future trials of ECMO for severe ARDS should strictly control for standard-of-care mechanical ventilation strategies in the control group and early transportation on ECMO for patients in the intervention arm.

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).

Usefulness of Cooling and Coronary Catheterization to Improve Survival in Out-of-Hospital Cardiac Arrest

Survival rates after out-of-hospital cardiac arrest (OHCA) continue to be poor. Recent evidence suggests that a more aggressive approach to postresuscitation care, in particular combining therapeutic hypothermia with early coronary intervention, can improve prognosis. We performed a single-center review of 125 patients who were resuscitated from OHCA in 2 distinct treatment periods, from 2002 to 2003 (control group) and from 2007 to 2009 (contemporary group). Patients in the contemporary group had a higher prevalence of cardiovascular risk factors but similar cardiac arrest duration and prehospital treatment (adrenaline administration and direct cardioversion). Rates of cardiogenic shock (48% vs 41%, p = 0.2) and decreased conscious state on arrival (77% vs 86%, p = 0.2) were similar in the 2 cohorts, as was the incidence of ST-elevation myocardial infarction (33% vs 43%, p = 0.1). The contemporary cohort was more likely to receive therapeutic hypothermia (75% vs 0%, p <0.01), coronary angiography (77% vs 45%, p <0.01), and percutaneous coronary intervention (38% vs 23%, p = 0.03). This contemporary therapeutic strategy was associated with better survival to discharge (64% vs 39%, p <0.01) and improved neurologic recovery (57% vs 29%, p <0.01) and was the only independent predictor of survival (odds ratio 5.5, 95% confidence interval 1.2 to 26.2, p = 0.03). Longer resuscitation time, presence of cardiogenic shock, and decreased conscious state were independent predictors of poor outcomes. In conclusion, modern management of OHCA, including therapeutic hypothermia and early coronary angiography is associated with significant improvement in survival to hospital discharge and neurologic recovery.

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.

Extracorporeal Membrane Oxygenation—Hemostatic Complications

The use of extracorporeal membrane oxygenation (ECMO) support for cardiac and respiratory failure has increased in recent years. Improvements in ECMO oxygenator and pump technologies have aided this increase in utilization. Additionally, reports of successful outcomes in supporting patients with respiratory failure during the 2009 H1N1 pandemic and reports of ECMO during cardiopulmonary resuscitation have led to increased uptake of ECMO. Patients requiring ECMO are a heterogenous group of critically ill patients with cardiac and respiratory failure. Bleeding and thrombotic complications remain a leading cause of morbidity and mortality in patients on ECMO. In this review, we describe the mechanisms and management of hemostatic, thrombotic and hemolytic complications during ECMO support.

Early decompressive craniectomy for patients with severe traumatic brain injury and refractory intracranial hypertension—A pilot randomized trial

PURPOSE The aims of this study were to test the feasibility and to assess potential recruitment rates in a pilot study preliminary to a phase III randomized trial of decompressive craniectomy surgery in patients with diffuse traumatic brain injury (TBI) and refractory intracranial hypertension. MATERIALS AND METHODS A study protocol was developed, inclusion and exclusion criteria were defined, and a standardized surgical technique was established. Neurologic outcomes were assessed 6 months after injury with a validated structured questionnaire and a single trained assessor blind to treatment group. RESULTS During the 8-month pilot study at a level 1 trauma center in Melbourne, Australia, 69 intensive care patients with severe TBI were assessed for inclusion. Six patients were eligible, and 5 (8%) were randomized. Six months after injury, 100% of patients received outcome assessments. Key improvements to the multicenter Decompressive Craniectomy study protocol were enabled by the pilot study. CONCLUSIONS In patients with severe TBI and refractory intracranial hypertension, the frequency of favorable neurologic outcomes (independent living) was low and similar to predicted values (40% favorable). A future multicenter phase III trial involving 18 neurotrauma centers with most sites conservatively recruiting at just 25% of the pilot study rate would require at least 5 years to achieve an estimated 210-patient sample size. Collaboration with neurotrauma centers in countries other than Australia and New Zealand would be required for such a phase III trial to be successful.

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.