Techniques to monitor respiratory drive and inspiratory effort Purpose of review There is increased awareness that derangements of respiratory drive and inspiratory effort are frequent and can result in lung and diaphragm injury together with dyspnea and sleep disturbances. This review aims to describe available techniques to monitor drive and effort. Recent findings Measuring drive and effort is necessary to quantify risk and implement strategies to minimize lung and the diaphragm injury by modifying sedation and ventilation. Evidence on the efficacy of such strategies is yet to be elucidated, but physiological and epidemiological data support the need to avoid injurious patterns of breathing effort. Some techniques have been used in research for decades (e.g., esophageal pressure or airway occlusion pressure), evidence on their practical utility is growing, and technical advances have eased implementation. More novel techniques (e.g., electrical activity of the diaphragm and ultrasound) are being investigated providing new insights on their use and interpretation. Summary Available techniques provide reliable measures of the intensity and timing of drive and effort. Simple, noninvasive techniques might be implemented in most patients and the more invasive or time-consuming in more complex patients at higher risk. We encourage clinicians to become familiar with technical details and physiological rationale of each for optimal implementation. Correspondence to Irene Telias, MD, Critical Care Department, St. Michael's Hospital, 30 Bond St., 4th Floor, Room 4-079, Toronto, ON, Canada M5B 1T8. Tel: +1 416 864 5686; e-mail: telias.irene@gmail.com Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

Evolving targets for sedation during mechanical ventilation Purposes of review Critically ill patients frequently require mechanical ventilation as part of their care. Administration of analgesia and sedation to ensure patient comfort and facilitate mechanical ventilation must be balanced against the known negative consequences of excessive sedation. The present review focuses on the current evidence for sedation management during mechanical ventilation, including choice of sedatives, sedation strategies, and special considerations for acute respiratory distress syndrome (ARDS). Recent findings The Society of Critical Care Medicine recently published their updated clinical practice guidelines for analgesia, agitation, sedation, delirium, immobility, and sleep in adult patients in the ICU. Deep sedation, especially early in the course of mechanical ventilation, is associated with prolonged time to liberation from mechanical ventilation, longer ICU stays, longer hospital stays, and increased mortality. Dexmedetomidine may prevent ICU delirium when administered nocturnally at low doses; however, it was not shown to improve mortality when used as the primary sedative early in the course of mechanical ventilation, though the majority of patients in the informing study failed to achieve the prescribed light level of sedation. In a follow up to the ACURASYS trial, deep sedation with neuromuscular blockade did not result in improved mortality compared to light sedation in patients with severe ARDS. Summary Light sedation should be targeted early in the course of mechanical ventilation utilizing daily interruptions of sedation and/or nursing protocol-based algorithms, even in severe ARDS. Correspondence to Bhakti K. Patel, MD, 5841 S. Maryland Avenue, Chicago, IL 60637, USA. Tel: +1 773 702 1000; fax: +1 773 702 4736; e-mail: bpatel@medicine.bsd.uchicago.edu Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

The role of computer-based clinical decision support systems to deliver protective mechanical ventilation Purpose of review Mechanical ventilation of adults and children with acute respiratory failure necessitates balancing lung and diaphragm protective ventilation. Computerized decision support (CDS) offers advantages in circumstances where complex decisions need to be made to weigh potentially competing risks, depending on the physiologic state of the patient. Recent findings Significant variability in how ventilator protocols are applied still exists and clinical data show that there continues to be wide variability in ventilator management. We have developed a CDS, which we are currently testing in a Phase II randomized controlled trial. The CDS is called Real-time Effort Driven ventilator management (REDvent). We will describe the rationale and methods for development of CDS for lung and diaphragm protective ventilation, using the REDvent CDS as an exemplar. Summary Goals for achieving compliance and physiologic objectives can be met when CDS instructions are simple and explicit, provide the clinician with the underlying rule set, permit acceptable reasons for declining and allow for iterative adjustments. Correspondence to Dr Robinder G. Khemani, MD, MsCI, Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Mailstop # 12, 4650 Sunset Blvd., Los Angeles, CA 90027, USA. Tel: +1 323 361 2376; e-mail: rkhemani@chla.usc.edu Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

NAVA and PAV+ for lung and diaphragm protection Purpose of review Complications of mechanical ventilation, such as ventilator-induced lung injury (VILI) and ventilator-induced diaphragmatic dysfunction (VIDD), adversely affect the outcome of critically ill patients. Although mostly studied during control ventilation, it is increasingly appreciated that VILI and VIDD also occur during assisted ventilation. Hence, current research focuses on identifying ways to monitor and deliver protective ventilation in assisted modes. This review describes the operating principles of proportional modes of assist, their implications for lung and diaphragm protective ventilation, and the supporting clinical data. Recent findings Proportional modes of assist, proportional assist ventilation, PAV, and neurally adjusted ventilatory assist, NAVA, deliver a pressure assist that is proportional to the patient's effort, enabling ventilation to be better controlled by the patient's brain. This control underlies the potential of proportional modes to avoid over-assist and under-assist, improve patient--ventilator interaction, and provide protective ventilation. Indeed, in clinical studies, proportional modes have been associated with reduced asynchronies, enhanced diaphragmatic recovery, and limitation of excessive tidal volume. Additionally, proportional modes facilitate better monitoring of the delivery of protective assisted ventilation. Summary Physiological rationale and clinical data suggest a potential role for proportional modes of assist in providing and monitoring lung and diaphragm protective ventilation. Correspondence to Katerina Vaporidi, MD, PhD, Department of Intensive Care, University of Crete, School of Medicine, office 8A4, Heraklio, Greece. Tel: +30 2810394729; e-mail: vaporidi@uoc.gr Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.co-criticalcare.com). Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

Monitoring respiratory mechanics during assisted ventilation Purpose of review Accurate monitoring of the mechanical properties of the respiratory system is crucial to understand the pathophysiological mechanisms of respiratory failure in mechanically ventilated patients, to optimize mechanical ventilation settings and to reduce ventilator-induced lung injury. However, although the assessment of respiratory mechanics is simple in patients undergoing fully controlled ventilation, it becomes quite challenging in the presence of spontaneous breathing activity. Aim of the present review is to describe how the different components of respiratory mechanics [resistance, static compliance, and intrinsic positive end-expiratory pressure (PEEP)] can be measured at the bedside during assisted modes of ventilation. Recent findings Available techniques for bedside measurement of resistance during assisted ventilation are complex and not commonly implemented. On the contrary, an increasing number of reports indicate that measurement of static compliance and intrinsic PEEP can be easily obtained, both with advanced monitoring systems (esophageal and gastric manometry, diaphragm electromyography, electrical impedance tomography) and, with some limitations, with simple airways occlusion maneuvers. Summary Assessment of respiratory mechanics in spontaneously breathing patients, with some limitations, is feasible and should be included in everyday clinical practice; however, more data are needed to understand the clinical relevance of the measures obtained during assisted ventilation. Correspondance to Giacomo Grasselli, Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy. Tel: +39 0255033258; fax: +39 0255033648; e-mail: giacomo.grasselli@unimi.it Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

Diaphragm protection: what should we target? Purpose of review Diaphragm weakness can impact survival and increases comorbidities in ventilated patients. Mechanical ventilation is linked to diaphragm dysfunction through several mechanisms of injury, referred to as myotrauma. By monitoring diaphragm activity and titrating ventilator settings, the critical care clinician can have a direct impact on diaphragm injury. Recent findings Both the absence of diaphragm activity and excessive inspiratory effort can result in diaphragm muscle weakness, and recent evidence demonstrates that a moderate level of diaphragm activity during mechanical ventilation improves ICU outcome. This supports the hypothesis that by avoiding ventilator overassistance and underassistance, the clinician can implement a diaphragm-protective ventilation strategy. Furthermore, eccentric diaphragm contractions and end-expiratory shortening could impact diaphragm strength as well. This review describes these potential targets for diaphragm protective ventilation. Summary A ventilator strategy that results in appropriate levels of diaphragm activity has the potential to be diaphragm-protective and improve clinical outcome. Monitoring respiratory effort during mechanical ventilation is becoming increasingly important. Correspondence to Tom Schepens, Department of Critical Care Medicine, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium. Tel.: +32 3 821 36 35;. e-mail: tom.schepens@uza.be Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

Searching for the optimal positive end-expiratory pressure for lung protective ventilation Purpose of review The optimal strategy for setting positive end-expiratory pressure (PEEP) has not been established. This review examines different approaches for setting PEEP to achieve lung-protective ventilation. Recent findings PEEP titration strategies commonly focus either on achieving adequate arterial oxygenation or reducing ventilator-induced lung injury from repetitive alveolar opening and closing, referred to as the open lung approach. Five recent trials of higher versus lower PEEP have not shown benefit with higher PEEP, and one of the five trials showed increased harm for patients treated with the open lung strategy. Evidence suggests that some patients may respond beneficially to higher PEEP by recruiting lung, whereas other patients do not recruit lung and merely overdistend previously open alveoli when higher PEEP is applied. A PEEP titration approach that differentiates PEEP responders from nonresponders and provides higher or lower PEEP accordingly has not been prospectively tested. Summary When compared, no method for setting PEEP has been proven superior to another. Based on recent studies, higher compared with lower PEEP has not improved clinical outcomes and worsened mortality in one study. Future research should focus on identifying feasible methods for assessing lung recruitability in response to PEEP to enrich future trials of PEEP strategies. Correspondence to Sarina K. Sahetya, MD, MHS, Division of Pulmonary and Critical Care Medicine, School of Medicine, Johns Hopkins University, 1830 E. Monument St, Suite 503, Baltimore, MD 21287, USA. Tel: +1 443 287 3354; e-mail: ssahety1@jhmi.edu Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.