Matthieu Schmidt

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).

Venoarterial extracorporeal membrane oxygenation support for refractory cardiovascular dysfunction during severe bacterial septic shock.

Objectives:Profound myocardial depression can occur during severe septic shock. Although good outcomes of venoarterial extracorporeal membrane oxygenation–treated children with refractory septic shock have been reported, little is known about adults’ outcomes. This study was designed to assess the outcomes and long-term health-related quality-of-life of patients supported by venoarterial extracorporeal membrane oxygenation for refractory cardiac and hemodynamic failure during severe septic shock. Design:A retrospective, single-center, observational study and a cross-sectional survey to assess health-related quality of life by the Short Form-36 questionnaire and frequencies of anxiety, depression and posttraumatic stress disorder symptoms by the Hospital Anxiety and Depression Scale and the Impact of Event Scale, respectively. Setting:A 26-bed tertiary intensive care unit in a university hospital. Patients:We evaluated the outcomes of patients who received venoarterial extracorporeal membrane oxygenation rescue therapy for refractory cardiovascular failure during bacterial septic shock. Results are expressed as medians (range). Measurements and Main Results:From January 2008 to September 2011, 14 patients, 45 years old (28–66), seven males, none with a history of left ventricular dysfunction, received venoarterial extracorporeal membrane oxygenation for septic shock refractory to conventional treatment, 24 hours (3–108) after shock onset. All exhibited severe myocardial dysfunction at extracorporeal membrane oxygenation implantation. Left ventricular ejection fraction was 16% (10% to 30%), cardiac index was 1.3 L/min/m2 (0.7–2.2 ) and systemic resistance vascular index was 3162 (2047–7685). All were receiving high-dose catecholamines and had signs of multiple organ failure: pH 7.16 (6.68–7.39), blood lactate 9 (2–17) mmol/L, PaO2/FIO2 87 (28–364), Simplified Acute Physiology Score III 84 (75–106) and Sepsis-Related Organ Failure Assessment score 18 (8–21). Twelve patients (86%) could be weaned off venoarterial extracorporeal membrane oxygenation after 5.5 days (2–12) days of support and 10 patients (71%) were discharged to home and were alive after a median follow-up of 13 months (3–43). All 10 survivors had normal left ventricular ejection fraction and reported good health-related quality of life at long-term follow-up. Conclusions:Venoarterial extracorporeal membrane oxygenation rescued more than 70% of the patients who developed refractory cardiovascular dysfunction during severe bacterial septic shock. Survivors reported good long-term quality of life. Venoarterial extracorporeal membrane oxygenation might represent a valuable therapeutic option for adults in severe septic shock with refractory cardiac and hemodynamic failure.

Neurally Adjusted Ventilatory Assist Increases Respiratory Variability and Complexity in Acute Respiratory Failure

Background:Neurally adjusted ventilatory assist (NAVA) is a partial ventilatory support mode where positive pressure is provided in relation to diaphragmatic electrical activity (EAdi). Central inspiratory activity is normally not monotonous, but it demonstrates short-term variability and complexity. The authors reasoned that NAVA should produce a more “natural” or variable breathing pattern than other modes. This study compared respiratory variability and complexity during pressure support ventilation (PSV) and NAVA. Methods:Flow and EAdi were recorded during routine PSV (tidal volume ∼6–8 ml/kg) and four NAVA levels (1–4 cm H2O/&mgr;VEAdi) in 12 intubated patients. Breath-by-breath variability of flow and EAdi-related variables was quantified by the coefficient of variation (CV) and autocorrelation analysis. Complexity of flow and EAdi was described using noise titration, largest Lyapunov exponent, Kolmogorov-Sinai entropy, and three-dimensional phase portraits. Results:Switching from PSV to NAVA increased the CV and decreased the autocorrelation for most flow-related variables in a dose-dependent manner (P < 0.05, partial &eegr;2 for the CV of mean inspiratory flow 0.642). The changes were less marked for EAdi. A positive noise limit was consistently found for flow and EAdi. Largest Lyapunov exponent and Kolmogorov-Sinai entropy for flow were greater during NAVA than PSV and increased with NAVA level (P < 0.05, partial &eegr;2 0.334 and 0.312, respectively). Largest Lyapunov exponent and Kolmogorov-Sinai entropy for EAdi were not influenced by ventilator mode. Conclusions:Compared with PSV, NAVA increases the breathing pattern variability and complexity of flow, whereas the complexity of EAdi is unchanged. Whether this improves clinical outcomes remains to be determined.

Dyspnea in mechanically ventilated critically ill patients.

Objectives:Ensuring the comfort of intensive care unit patients is crucial. Although control of pain has been extensively addressed in this setting, data on dyspnea in mechanically ventilated patients are scant. The objective of this study was to assess the prevalence of dyspnea in mechanically ventilated patients, identify its clinical correlates, and examine its impact on clinical outcomes. Design:Prospective 6-month observational study. Setting:Two medical intensive care units within university hospitals. Participants:Intubated or tracheotomized patients who were mechanically ventilated for >24 hrs. We enrolled 96 patients (age, 61 ± 18 yrs; Simplified Acute Physiology Score II 43 [interquartile range, 31–60]) as soon as they could answer symptom-related questions. Dyspnea was evaluated on a “yes–no” basis; if yes, it was followed by a visual analog scale and descriptor choice (“air hunger” and/or “respiratory effort”). Pain and anxiety were also assessed by visual analog scales. Interventions:Ventilator settings adjustment in dyspneic patients. Measurements and Main Results:Forty-five patients (47%) reported dyspnea (respiratory effort in seven cases, air hunger in 15, both in 16, and neither of these in seven). Dyspneic and nondyspneic patients did not differ in terms of age, Simplified Acute Physiology Score II, indication for mechanical ventilation, respiratory rate, clinical examination, chest radiograph, or blood gases. Dyspnea was significantly associated with anxiety (odd ratio [OR], 8.84; 95% confidence interval [CI], 3.26–24.0), assist-control ventilation (OR, 4.77; 95% CI, 1.60–4.3), and heart rate (OR, 1.33 per 10 beats/min; 95% CI, 1.02–1.75). Adjusting ventilator settings improved dyspnea in 35% of patients. Successful extubation within 3 days was significantly less frequent in patients whose dyspnea failed to recede after adjusting ventilator settings (five [17%] vs. 27 [40%]; p = .034). Conclusions:Dyspnea is frequent, intense, and strongly associated with anxiety in mechanically ventilated patients. It can be sensitive to ventilator settings and seems to be associated with delayed extubation.

Having a loved one in the ICU: the forgotten family.

Purpose of reviewAn appreciation of the post-ICU burden for family members, as well as the ways to prevent and minimize their symptoms of stress, anxiety, and depression. Recent findingsThe long-term consequences of critical illness are growing in importance as the aging population increases its demand for critical care, and as the short-term mortality after critical illness decreases. Recently, postintensive care syndrome family was proposed as a new term for this cluster of psychological complications. Critical care providers are now recognizing the need to also address the psychological needs of the relatives earlier after ICU admission. SummaryA high proportion of family members present with symptoms of anxiety (70%) and depression (35%). Acute stress disorder and posttraumatic stress disorder (PTSD) related symptoms are also common. These symptoms are significantly more frequent when the relative is a spouse, or in bereaved family members. Few long-term data are available. However, in family members of dying patients, 1 year after the loss, up to 40% of them present with criteria for psychiatric illness such as generalized anxiety, major depressive disorders, or complicated grief. Prevention of post-ICU burden, mostly based on communication strategies, has been proposed to assist relatives.

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.

Venovenous extracorporeal membrane oxygenation for acute respiratory failure: A clinical review from an international group of experts

Despite expensive life-sustaining interventions delivered in the ICU, mortality and morbidity in patients with acute respiratory failure (ARF) remain unacceptably high. Extracorporeal membrane oxygenation (ECMO) has emerged as a promising intervention that may provide more efficacious supportive care to these patients. Improvements in technology have made ECMO safer and easier to use, allowing for the potential of more widespread application in patients with ARF. A greater appreciation of the complications associated with the placement of an artificial airway and mechanical ventilation has led clinicians and researchers to seek viable alternatives to providing supportive care in these patients. Thus, this review will summarize the current knowledge regarding the use of venovenous (VV)-ECMO for ARF and describe some of the recent controversies in the field, such as mechanical ventilation, anticoagulation and transfusion therapy, and ethical concerns in patients supported with VV-ECMO.

Unrecognized suffering in the ICU: addressing dyspnea in mechanically ventilated patients.

BackgroundIntensive care unit (ICU) patients are exposed to many sources of discomfort. Although increasing attention is being given to the detection and treatment of pain, very little is given to the detection and treatment of dyspnea (defined as “breathing discomfort”).MethodsPublished information on the prevalence, mechanisms, and potential negative impacts of dyspnea in mechanically ventilated patients are reviewed. The most appropriate tools to detect and quantify dyspnea in ICU patients are also assessed. Results/ConclusionsGrowing evidence suggests that dyspnea is a frequent issue in mechanically ventilated ICU patients, is highly associated with anxiety and pain, and is improved in many patients by altering the ventilator settings.ConclusionsFuture studies are needed to better delineate the impact of dyspnea in the ICU and to define diagnostic, monitoring and therapeutic protocols.