Laurent Brochard

Position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients

The use of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory failure (ARF) in adults is growing rapidly given recent advances in technology, even though there is controversy regarding the evidence justifying its use. Because ECMO is a complex, high-risk, and costly modality, at present it should be conducted in centers with sufficient experience, volume, and expertise to ensure it is used safely. This position paper represents the consensus opinion of an international group of physicians and associated health-care workers who have expertise in therapeutic modalities used in the treatment of patients with severe ARF, with a focus on ECMO. The aim of this paper is to provide physicians, ECMO center directors and coordinators, hospital directors, health-care organizations, and regional, national, and international policy makers a description of the optimal approach to organizing ECMO programs for ARF in adult patients. Importantly, this will help ensure that ECMO is delivered safely and proficiently, such that future observational and randomized clinical trials assessing this technique may be performed by experienced centers under homogeneous and optimal conditions. Given the need for further evidence, we encourage restraint in the widespread use of ECMO until we have a better appreciation for both the potential clinical applications and the optimal techniques for performing ECMO.

Effect of Noninvasive Ventilation on Tracheal Reintubation Among Patients With Hypoxemic Respiratory Failure Following Abdominal Surgery: A Randomized Clinical Trial

IMPORTANCE It has not been established whether noninvasive ventilation (NIV) reduces the need for invasive mechanical ventilation in patients who develop hypoxemic acute respiratory failure after abdominal surgery. OBJECTIVE To evaluate whether noninvasive ventilation improves outcomes among patients developing hypoxemic acute respiratory failure after abdominal surgery. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, parallel-group clinical trial conducted between May 2013 and September 2014 in 20 French intensive care units among 293 patients who had undergone abdominal surgery and developed hypoxemic respiratory failure (partial oxygen pressure <60 mm Hg or oxygen saturation [SpO2] ≤90% when breathing room air or <80 mm Hg when breathing 15 L/min of oxygen, plus either [1] a respiratory rate above 30/min or [2] clinical signs suggestive of intense respiratory muscle work and/or labored breathing) if it occurred within 7 days after surgical procedure. INTERVENTIONS Patients were randomly assigned to receive standard oxygen therapy (up to 15 L/min to maintain SpO2 of 94% or higher) (n = 145) or NIV delivered via facial mask (inspiratory pressure support level, 5-15 cm H2O; positive end-expiratory pressure, 5-10 cm H2O; fraction of inspired oxygen titrated to maintain SpO2 ≥94%) (n = 148). MAIN OUTCOMES AND MEASURES The primary outcome was tracheal reintubation for any cause within 7 days of randomization. Secondary outcomes were gas exchange, invasive ventilation-free days at day 30, health care-associated infections, and 90-day mortality. RESULTS Among the 293 patients (mean age, 63.4 [SD, 13.8] years; n=224 men) included in the intention-to-treat analysis, reintubation occurred in 49 of 148 (33.1%) in the NIV group and in 66 of 145 (45.5%) in the standard oxygen therapy group within+ 7 days after randomization (absolute difference, -12.4%; 95% CI, -23.5% to -1.3%; P = .03). Noninvasive ventilation was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (25.4 vs 23.2 days; absolute difference, -2.2 days; 95% CI, -0.1 to 4.6 days; P = .04), while fewer patients developed health care-associated infections (43/137 [31.4%] vs 63/128 [49.2%]; absolute difference, -17.8%; 95% CI, -30.2% to -5.4%; P = .003). At 90 days, 22 of 148 patients (14.9%) in the NIV group and 31 of 144 (21.5%) in the standard oxygen therapy group had died (absolute difference, -6.5%; 95% CI, -16.0% to 3.0%; P = .15). There were no significant differences in gas exchange. CONCLUSIONS AND RELEVANCE Among patients with hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of tracheal reintubation within 7 days. These findings support use of NIV in this setting. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01971892.

The "baby lung" became an adult.

The baby lung was originally defined as the fraction of lung parenchyma that, in acute respiratory distress syndrome (ARDS), still maintains normal inflation. Its size obviously depends on ARDS severity and relates to the compliance of the respiratory system. CO2 clearance and blood oxygenation primarily occur within the baby lung. While the specific compliance suggests the intrinsic mechanical characteristics to be nearly normal, evidence from positron emission tomography suggests that at least a part of the well-aerated baby lung is inflamed. The baby lung is more a functional concept than an anatomical one; in fact, in the prone position, the baby lung “shifts” from the ventral lung regions toward the dorsal lung regions while usually increasing its size. This change is associated with better gas exchange, more homogeneously distributed trans-pulmonary forces, and a survival advantage. Positive end expiratory pressure also increases the baby lung size, both allowing better inflation of already open units and adding new pulmonary units. Viewed as surrogates of stress and strain, tidal volume and plateau pressures are better tailored to baby lung size than to ideal body weight. Although less information is available for the baby lung during spontaneous breathing efforts, the general principles regulating the safety of ventilation are also applicable under these conditions.

Partial Neuromuscular Blockade during Partial Ventilatory Support in Sedated Patients with High Tidal Volumes

Rationale: Controlled mechanical ventilation is used to deliver lung‐protective ventilation in patients with acute respiratory distress syndrome. Despite recognized benefits, such as preserved diaphragm activity, partial support ventilation modes may be incompatible with lung‐protective ventilation due to high Vt and high transpulmonary pressure. As an alternative to high‐dose sedatives and controlled mechanical ventilation, pharmacologically induced neuromechanical uncoupling of the diaphragm should facilitate lung‐protective ventilation under partial support modes. Objectives: To investigate whether partial neuromuscular blockade can facilitate lung‐protective ventilation while maintaining diaphragm activity under partial ventilatory support. Methods: In a proof‐of‐concept study, we enrolled 10 patients with lung injury and a Vt greater than 8 ml/kg under pressure support ventilation (PSV) and under sedation. After baseline measurements, rocuronium administration was titrated to a target Vt of 6 ml/kg during neurally adjusted ventilatory assist (NAVA). Thereafter, patients were ventilated in PSV and NAVA under continuous rocuronium infusion for 2 hours. Respiratory parameters, hemodynamic parameters, and blood gas values were measured. Measurements and Main Results: Rocuronium titration resulted in significant declines of Vt (mean ± SEM, 9.3 ± 0.6 to 5.6 ± 0.2 ml/kg; P < 0.0001), transpulmonary pressure (26.7 ± 2.5 to 10.7 ± 1.2 cm H2O; P < 0.0001), and diaphragm electrical activity (17.4 ± 2.3 to 4.5 ± 0.7 &mgr;V; P < 0.0001), and could be maintained under continuous rocuronium infusion. During titration, pH decreased (7.42 ± 0.02 to 7.35 ± 0.02; P < 0.0001), and mean arterial blood pressure increased (84 ± 6 to 99 ± 6 mm Hg; P = 0.0004), as did heart rate (83 ± 7 to 93 ± 8 beats/min; P = 0.0004). Conclusions: Partial neuromuscular blockade facilitates lung‐protective ventilation during partial ventilatory support, while maintaining diaphragm activity, in sedated patients with lung injury.

Respiratory support in patients with acute respiratory distress syndrome: An expert opinion

Acute respiratory distress syndrome (ARDS) is a common condition in intensive care unit patients and remains a major concern, with mortality rates of around 30–45% and considerable long-term morbidity. Respiratory support in these patients must be optimized to ensure adequate gas exchange while minimizing the risks of ventilator-induced lung injury. The aim of this expert opinion document is to review the available clinical evidence related to ventilator support and adjuvant therapies in order to provide evidence-based and experience-based clinical recommendations for the management of patients with ARDS.

Recovery after critical illness: putting the puzzle together-a consensus of 29

In this review, we seek to highlight how critical illness and critical care affect longer-term outcomes, to underline the contribution of ICU delirium to cognitive dysfunction several months after ICU discharge, to give new insights into ICU acquired weakness, to emphasize the importance of value-based healthcare, and to delineate the elements of family-centered care. This consensus of 29 also provides a perspective and a research agenda about post-ICU recovery.

An international phase iii randomised trial on the efficacy of helium/oxygen during spontaneous breathing and intermittent non-invasive ventilation for severe exacerbations of chronic obstructive pulmonary disease (the E.C.H.O.(ICU)trial).

Due to its reduced density, Helium/Oxygen (He/O2) reduces the work of breathing, intrinsic PEEP and hypercapnia more than Air/O2 during non-invasive ventilation (NIV) in COPD exacerbations [1, 2]. Two prospective, randomized multicenter trials were inconclusive in showing a benefit of He/O2 NIV on outcome (intubation, mortality, length of stay (LOS) in ICU) but were potentially underpowered [3, 4].

Inspiratory Muscle Rehabilitation in Critically Ill Adults. A Systematic Review and Meta-Analysis

Rationale: Respiratory muscle weakness is common in critically ill patients; the role of targeted inspiratory muscle training (IMT) in intensive care unit rehabilitation strategies remains poorly defined. Objectives: The primary objective of the present study was to describe the range and tolerability of published methods for IMT. The secondary objectives were to determine whether IMT improves respiratory muscle strength and clinical outcomes in critically ill patients. Methods: We conducted a systematic review to identify randomized and nonrandomized studies of physical rehabilitation interventions intended to strengthen the respiratory muscles in critically ill adults. We searched the MEDLINE, Embase, HealthSTAR, CINAHL, and CENTRAL databases (inception to September Week 3, 2017) and conference proceedings (2012 to 2017). Data were independently extracted by two authors and collected on a standardized report form. Results: A total of 28 studies (N = 1,185 patients) were included. IMT was initiated during early mechanical ventilation (8 studies), after patients proved difficult to wean (14 studies), or after extubation (3 studies), and 3 other studies did not report exact timing. Threshold loading was the most common technique; 13 studies employed strength training regimens, 11 studies employed endurance training regimens, and 4 could not be classified. IMT was feasible, and there were few adverse events during IMT sessions (nine studies; median, 0%; interquartile range, 0‐0%). In randomized trials (n = 20), IMT improved maximal inspiratory pressure compared with control (15 trials; mean increase, 6 cm H2O; 95% confidence interval [CI], 5‐8 cm H2O; pooled relative ratio of means, 1.19; 95% CI, 1.14‐1.25) and maximal expiratory pressure (4 trials; mean increase, 9 cm H2O; 95% CI, 5‐14 cm H2O). IMT was associated with a shorter duration of ventilation (nine trials; mean difference, 4.1 d; 95% CI, 0.8‐7.4 d) and a shorter duration of weaning (eight trials; mean difference, 2.3 d; 95% CI, 0.7‐4.0 d), but confidence in these pooled estimates was low owing to methodological limitations, including substantial statistical and methodological heterogeneity. Conclusions: Most studies of IMT in critically ill patients have employed inspiratory threshold loading. IMT is feasible and well tolerated in critically ill patients and improves both inspiratory and expiratory muscle strength. The impact of IMT on clinical outcomes requires future confirmation.

Treatment limitations in the era of ECMO

Once relegated to the fringes of medicine, the use of extracorporeal membrane oxygenation (ECMO) in adults with severe respiratory or cardiac failure is now increasing at an extraordinary pace. ECMO is perceived by many as life-saving, and this growth is continuing despite a paucity of widely accepted evidence demon strating benefit. Without such evidence, our obligation to carefully assess the place of this technology in patient care is heightened. In this rapidly evolving area, how do we decide when to offer such high-risk, resource-intensive interventions, and when to withhold or withdraw them? When making complex medical decisions, we should first decide what our interventions might offer in terms of survival and quality of life. We should then engage with our patients and their surrogates, providing them options within a clinical context while, in turn, they provide us with guidance on their values and goals. Together, we decide which life-sustaining options have the potential to achieve these goals. Importantly, clinicians should not abrogate their responsibility to serve as a guide in this process, imparting judgments that are both medically sound and palatable to the patient. Clinicians should avoid the temptation to offer a menu of specific therapeutic options to patients and surrogates, forcing them to make difficult medical decisions without adequate guidance, and opening the door to potentially contradictory and inappropriate treatments. One of the challenges that our health-care systems will face with the increasing use of ECMO will be the inclination to broaden our current code status orders to incorporate ECMO. Many institutions offer orders, such as “do not resuscitate (DNR) and do not intubate (DNI)” as well as “DNR, intubation ok”. What are the implications of including ECMO explicitly in these discussions? When the prognosis is uncertain, is it possible to limit treatment, yet proceed with ECMO? Could a patient have a DNR order but accept ECMO? Although this would seem inconsistent, and in many scenarios be inappropriate, the division of life-sustaining treatments into those we will provide and those we will not, is not without precedent. We might choose to withhold cardiopulmonary resuscitation (CPR), yet initiate other life-sustaining measures such as invasive mechanical ventilation. Clearly, such a decision to proceed with ECMO would have to be made with very specific, potentially achievable goals in mind. On the other hand, CPR could be considered in some patients in whom ECMO would not. The clearest example is the use of ECMO to support the circulation during cardiac arrest, so-called extracorporeal CPR. Circulatory arrest— and therefore circulatory death—might be suspended by the initiation of extracorporeal CPR in an attempt to buy time to reverse the culpable pathology. The provision of conventional CPR, and withholding of extracorporeal CPR, in centres that offer it, is a reasonable approach. Could a patient have a DNI order but accept extracorporeal CO2 removal? A scenario we are very likely to confront—one that has already played out in medical literature—is the use of extracorporeal CO2 removal in patients with acute respiratory failure, in lieu of invasive mechanical ventilation, precisely because the patient has chosen to forgo invasive mechanical ventilation. The promise of extracorporeal CO2 removal is that it is potentially less invasive and lower risk than ECMO. Yet it is not without risks. So long as the patient or surrogate decision makers are well informed of the risks, the degree of invasiveness that they choose to tolerate is a personal decision. However, we might find ourselves wrestling with additional issues if we choose this route. When a patient with an acute exacerbation of advanced chronic obstructive pulmonary disease, who is failing to respond to non-invasive ventilation, simultaneously chooses extracorporeal CO2 removal along with a DNI order, what happens if she becomes stable and comfortable on extracorporeal CO2 removal but cannot be weaned from it? Different from invasive mechanical ventilation, dependence on extracorporeal CO2 removal currently confines the patient to an intensive care unit (ICU). What options exist at that point? Continuation of extracorporeal CO2 removal until it fails to support life could be the default for many. Invasive mechanical ventilation and tracheostomy would allow continued survival outside the ICU, but might not be consistent with the patient’s wishes. Finally, withdrawal of support or transitioning to comfort care measures might be preferable. This potential unintended consequence, and the patient’s preferences for how to approach the situation, should ideally be discussed before extracorporeal CO2 removal is underway. More provocative still is the notion that ECMO is now a special class of device requiring us to delineate when we would and would not initiate it when discussing goals †Participants listed in the appendix

Ten recent advances that could not have come about without applying physiology

Fluid responsiveness assesses preload reserve not preload. Static estimates of cardiac preload do not predict preload responsiveness [1]. Increasing stroke volume (SV) in response to increasing preload defines preload responsiveness. Both positive-pressure breathing and passive leg raising (PLR), by transiently altering preload, can be used to predict volume responsiveness without giving fluids. Arterial pulse pressure variation (PPV) or left ventricular (LV) SV variation (SVV) [10–13 % in patients on positive-pressure ventilation (Vt C8 ml/kg) or an increase in cardiac output[10 % to PLR in any subject identifies volume responders [2, 3]. Similarly, transient end-tidal expired CO2 increases can be used as a surrogate for changes in cardiac output in response to PLR [3].