Faculty Bibliography

Sedation is often required to facilitate comfort and provide necessary care for patients who are critically ill and require mechanical ventilation. Intravenous sedatives are the current standard of care in this patient population. Inhaled volatile agents that are routinely used for general anesthesia, like isoflurane and sevoflurane, are also being explored for their potential role in the ICU setting. Already, inhaled volatile agents are prescribed for routine ICU sedation in several countries, though their use for ICU sedation is not approved by United States regulatory authorities as of the time of this writing. The efficacy and safety profiles of inhaled sedatives for short-term use are well understood through decades of experience in the operating room. Their rapid onset and elimination via the lungs, potential opioid-sparing effects, and preservation of spontaneous breathing make them intriguing potential alternatives or adjuncts to standard-of-care sedation during critical illness. Technological advancements, consisting of compact vaporizers, volatile agent reflectors, and scavenger systems, allow the delivery of inhaled sedatives via modern ICU ventilators. However, these systems require specialized clinical training and considerations. Rigorous clinical trials evaluating the use of inhaled volatile agents for prolonged sedation of patients receiving mechanical ventilation remain limited, and whether these theoretical advantages translate to patient-centered benefit, relative to intravenous agents, remains unknown. Recent findings suggest prolonged deep sedation with inhaled sevoflurane predisposes to nephrogenic diabetes insipidus and acute kidney injury during critical illness, and that it is potentially harmful in patients with ARDS. Isoflurane may have a more favorable safety profile, but rigorous data are sparse on isoflurane use for more than a few days. This narrative review evaluates the evidence regarding the use of inhaled sedatives in patients in ICU who require mechanical ventilation. It also provides an overview of the clinical and technical aspects of this therapy to inform health care providers of a novel option, in many countries, for the sedation of patients undergoing mechanical ventilation.

BACKGROUND:Intensive care unit (ICU) staffing models increasingly use advanced practice providers (APPs), with unclear implications for clinical practice patterns. Sedation strategy is a modifiable determinant of clinical outcomes that might differ by staffing model. METHODS:This retrospective cohort study evaluated adults admitted to two medical ICUs in a quaternary teaching hospital, whose staffing differed only by APPs or residents. Patients requiring invasive ventilation for at least 48 h were included. The primary outcome was association of staffing model with sedative exposure during the first week of mechanical ventilation. Time to extubation and vital status at discharge were also assessed. RESULTS:Of 337 included patients, 96 % received continuous sedation on the day of intubation. Admission to the APP ICU was associated with significantly lower benzodiazepine exposure (adjusted OR 0.63; 95 % CI 0.40-0.99; p = 0.04) and higher propofol exposure (adjusted OR 1.73; 95 % CI 1.07-2.79; p = 0.03) on day of intubation. Cumulative benzodiazepine and opioid exposures over the first week after intubation were significantly less, and cumulative propofol exposure significantly more in the APP ICU despite similar sedation depth achieved between ICUs. Receipt of propofol on the first day was associated with shorter time to extubation (adjusted HR 1.45, 95 % CI 1.07-1.98; p = 0.02) and lower in-hospital mortality (adjusted OR 0.55, 95 % CI 0.33-0.93; p = 0.02). CONCLUSION/CONCLUSIONS:Patients admitted to an APP-staffed ICU were more likely to have sedation management reflective of best practice, and this practice was associated with shorter time to extubation and lower mortality.

RATIONALE/BACKGROUND:Excessive stress (distending pressure), strain (volume deformation), and drop in inspiratory alveolar pressure are proposed mechanisms for patient self-inflicted lung injury. OBJECTIVES/OBJECTIVE:To dissect the influence of inspiratory effort, respiratory mechanics, and ventilation mode on lung stress, strain, and drop in inspiratory alveolar pressure; and explore their impact on oxygenation and lung compliance. METHODS:International cohort study analyzing respiratory recordings (esophageal pressure) of patients with acute hypoxemic respiratory failure. Association between muscular pressure (Pmus), surrogates of stress (driving trans-alveolar pressure), strain (tidal volume), and inspiratory alveolar pressure relative to PEEP were explored with mixed-models, including interactions for ventilation mode, respiratory system elastance, and synchrony. Association between these and changes in oxygenation and lung compliance were explored. MEASUREMENTS AND MAIN RESULTS/RESULTS:O, p<0.001). Volume-control ventilation showed less increase in stress and strain surrogates than pressure-targeted modes, but more drop in alveolar pressure (p<0.001, Pmus:mode interaction). Breath-stacking was infrequent and associated with higher stress. Lower inspiratory alveolar pressure relative to PEEP was associated with subsequent worsening oxygenation (p=0.04) and higher stress with worsening lung compliance (p=0.023). CONCLUSION/CONCLUSIONS:Strong efforts are associated with high surrogates for lung stress, strain, and lower inspiratory alveolar pressure relative to PEEP, differently according to the mode of ventilation, being associated with subsequent worsening oxygenation and lung compliance.

INTRODUCTION/BACKGROUND:Sepsis is a major cause of death both globally and in the United States. Early identification and treatment of sepsis are crucial for improving patient outcomes. International guidelines recommend hospital sepsis screening programmes, which are commonly implemented in the electronic health record (EHR) as an interruptive sepsis screening alert based on systemic inflammatory response syndrome (SIRS) criteria. Despite widespread use, it is unknown whether these sepsis screening and alert tools improve the delivery of high-quality sepsis care. METHODS AND ANALYSIS/METHODS:The Sepsis Electronic Prompting for Timely Intervention and Care (SEPTIC) master protocol will study two distinct populations in separate trials: emergency department (ED) patients (SEPTIC-ED) and inpatients (SEPTIC-IP). The SEPTIC trials are pragmatic, multicentre, blinded, randomised controlled trials, with equal allocation to compare four SIRS-based sepsis screening alert groups: no alerts (control), nurse alerts only, prescribing clinician alerts only, or nurse and prescribing clinician alerts. Randomisation will be at the patient level. SEPTIC will be performed at eight acute-care hospitals in the greater New York City area and enrol patients at least 18 years old. The primary outcome is the percentage of patients with completion of a modified Surviving Sepsis Campaign (SSC) hour-1 bundle within 3 hours of the first SIRS alert. Secondary outcomes include time from first alert to completion of a modified SSC hour-1 bundle, time from first alert to individual bundle component order and completion, intensive care unit (ICU) transfer, hospital discharge disposition, inpatient mortality at 90 days, positive blood cultures (bacteraemia), adverse antibiotic events, sepsis diagnoses and septic shock diagnoses. ETHICS AND DISSEMINATION/BACKGROUND:Ethics approval was obtained from the Columbia University Institutional Review Board (IRB) serving as a single IRB. Results will be disseminated in peer-reviewed journal(s), scientific meeting(s) and via social media. TRIAL REGISTRATION NUMBER/BACKGROUND:ClinicalTrials.gov: NCT06117605 and NCT06117618.

UNLABELLED:Monitoring inspiratory drive and effort may aid proper selection and setting of respiratory support in patients with acute respiratory failure (ARF), whether they are intubated or not. Although diaphragmatic electrical activity (EAdi) and esophageal manometry can be considered the reference methods for assessing respiratory drive and inspiratory effort, respectively, various alternative techniques exist, each with distinct advantages and limitations. This narrative review provides a comprehensive overview of bedside methods to assess respiratory drive and effort, with a primary focus on patients with ARF. First, EAdi and esophageal manometry are described and discussed as reference techniques. Then, alternative methods are categorized along the neuromechanical pathway from inspiratory drive to muscular effort into three groups: (1) techniques assessing the respiratory drive: airway occlusion pressure (P0.1), mean inspiratory flow (Vt/Ti) and respiratory muscle surface electromyography (sEMG); (2) techniques assessing the respiratory muscle effort: whole-breath occlusion pressure (ΔPocc), pressure-muscle index (PMI), nasal pressure swing (ΔPnose), diaphragm ultrasonography (USdi), central venous pressure swing (ΔCVP), breathing effort (BREF) models, and flow index; (3) techniques and clinical parameters assessing the consequences of effort: tidal volume (Vt), electrical impedance tomography (EIT), dyspnea. For each, we summarize the physiological rationale, measurement methodology, interpretation of results, and key limitations. SUPPLEMENTARY INFORMATION:The online version contains supplementary material available at 10.1186/s13054-025-05526-0.

BACKGROUND:Patients undergoing invasive mechanical ventilation often require pharmacologic sedation to facilitate tolerance of this life-sustaining intervention, but sedatives currently used in routine care have substantial limitations. Isoflurane is an inhaled volatile anesthetic with pharmacologic properties potentially suitable to sedation of ventilator-dependent critically ill patients, but need for specialized drug administration equipment has limited its use historically to general anesthesia in the operating theatre. This trial will evaluate isoflurane, administered using a novel drug delivery system, for sedation of ventilator-dependent adult intensive care unit (ICU) patients in the United States (US). METHODS:The Inhaled Sedation versus Propofol in Respiratory Failure in the ICU (INSPiRE-ICU2) is a phase 3, multicenter, randomized, controlled, assessor-blinded non-inferiority trial that will evaluate efficacy and safety of inhaled isoflurane delivered via the Sedaconda ACD-S, compared to intravenous propofol, for sedation of mechanically ventilated adult ICU patients. At 16 US hospitals, 235 enrolled patients requiring continuous sedation during invasive mechanical ventilation will be randomized in 1.5:1 ratio to inhaled isoflurane or intravenous propofol for sedation. Treatment duration is expected to be at least 12 h and may last up to 48 (± 6) h or until no longer needing continuous sedation, whichever occurs first. The primary endpoint is the percentage of time sedation depth is maintained within the targeted range (Richmond Agitation Sedation Scale - 1 to - 4), in the absence of rescue sedation, during the treatment period. Secondary superiority outcomes include opioid exposure, wake-up time, cognitive recovery after end-of-treatment, and preservation of spontaneous breathing effort. DISCUSSION/CONCLUSIONS:The INSPiRE-ICU2 trial will help determine the potential role of isoflurane for sedation of ventilator-dependent adult patients in the ICU. Key trial design features, including adoption of the estimand framework and blinded assessments of sedation depth, pain, and cognitive recovery, will ensure a rigorous evaluation of isoflurane for ICU sedation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05327296. First registered on April 5, 2022.

This review explores the complex interactions between sedation and invasive ventilation and examines the potential of volatile anesthetics for lung- and diaphragm-protective sedation. In the early stages of invasive ventilation, many critically ill patients experience insufficient respiratory drive and effort, leading to compromised diaphragm function. Compared with common intravenous agents, inhaled sedation with volatile anesthetics better preserves respiratory drive, potentially helping to maintain diaphragm function during prolonged periods of invasive ventilation. In turn, higher concentrations of volatile anesthetics reduce the size of spontaneously generated tidal volumes, potentially reducing lung stress and strain and with that the risk of self-inflicted lung injury. Taken together, inhaled sedation may allow titration of respiratory drive to maintain inspiratory efforts within lung- and diaphragm-protective ranges. Particularly in patients who are expected to require prolonged invasive ventilation, in whom the restoration of adequate but safe inspiratory effort is crucial for successful weaning, inhaled sedation represents an attractive option for lung- and diaphragm-protective sedation. A technical limitation is ventilatory dead space introduced by volatile anesthetic reflectors, although this impact is minimal and comparable to ventilation with heat and moisture exchangers. Further studies are imperative for a comprehensive understanding of the specific effects of inhaled sedation on respiratory drive and effort and, ultimately, how this translates into patient-centered outcomes in critically ill patients.

BACKGROUND:Recruitment maneuvers are used in patients with ARDS to enhance oxygenation and lung mechanics. Heterogeneous lung and chest-wall mechanics lead to unpredictable transpulmonary pressures and could impact recruitment maneuver success. Tailoring care based on individualized transpulmonary pressure might optimize recruitment, preventing overdistention. This study aimed to identify the optimal transpulmonary pressure for effective recruitment and to explore its association with baseline characteristics. METHODS:We performed post hoc analysis on the Esophageal Pressure Guided Ventilation (EpVent2) trial. We estimated the dose-response relationship between end-recruitment end-inspiratory transpulmonary pressure and the change in lung elastance after a recruitment maneuver by using logistic regression weighted by a generalized propensity score. A positive change in lung elastance was indicative of overdistention. We examined how patient characteristics, disease severity markers, and respiratory parameters predict transpulmonary pressure by using multivariate linear regression models and dominance analyses. RESULTS: CONCLUSIONS:Higher end-recruitment transpulmonary pressure increases the volume of recruitment but raises the risk of overdistention, providing the rationale for transpulmonary pressure to be used as a clinical target. Predictors, for example, body mass index, could guide recruitment maneuver individualization to balance adequate volume gain with overdistention.