Michael Chaim Sklar

Background: We aimed to evaluate the comparative effectiveness and safety of various sedative agents used for endotracheal intubation of the critically ill patient in the emergency department, intensive care unit, operating room, and pre-hospital setting. We performed a systematic review and network meta-analysis to enable direct and indirect comparisons between available medications.Methods: We searched MEDLINE, EMBASE, PubMed, Cochrane, and trial registries from inception to December 10, 2025 for Randomized controlled trials (RCTs) comparing two or more sedative agents in critically ill adults or children undergoing endotracheal intubation. Outcomes of interest were hemodynamic instability during intubation, hypoxemia, cardiac arrest, mortality, intensive care unit and hospital length of stay, vasopressor use, adrenal insufficiency, and first-pass success. Reviewers screened, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool independently and in duplicate. We performed frequentist random-effects model network meta-analysis and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty in estimates.Findings: We included 21 RCTs enrolling 5,944 patients across Intensive Care Unit, Emergency Department, Operating Room, and pre-hospital settings. Compared with etomidate, there is probably more hemodynamic instability during intubation with ketamine (RR 1.31, 95% CI 1.15-1.48; moderate certainty). Ketamine-propofol may decrease hemodynamic instability during intubation compared with etomidate (RR 0.44, 95% CI 0.27-0.72; low certainty) and ketamine (RR 0.34, 95% CI 0.21-0.56; low certainty). Compared with etomidate, ketamine may decrease the need for the initiation of post-intubation continuous infusion vasopressors (RR 0.80, 95% CI 0.50-1.28; low certainty). Etomidate caused increased adrenal suppression compared with other agents. Interpretation: When considering sedation agents for endotracheal intubation of the critically ill, etomidate probably causes less hemodynamic instability during intubation when compared with ketamine. However, etomidate may increase the need for the initiation of post-intubation continuous infusion vasopressors when compared with ketamine and increases adrenal suppression. Ketamine-propofol may decrease hemodynamic instability during intubation when compared with etomidate and ketamine though the available evidence is too limited and uncertain to support firm conclusions and further randomized trials are needed.

Purpose: Pain may pose significant challenges in the intensive care unit, especially in mechanically ventilated patients. Methadone has recently emerged as an alternative option for eliciting acute analgesia. In this systematic review, we evaluated the use of methadone in mechanically ventilated patients in the intensive care unit. Source: We searched MEDLINE, EMBASE, Wiley’s Cochrane […] ABSTRACT Purpose: Pain may pose significant challenges in the intensive care unit, especially in mechanically ventilated patients. Methadone has recently emerged as an alternative option for eliciting acute analgesia. In this systematic review, we evaluated the use of methadone in mechanically ventilated patients in the intensive care unit. Source: We searched MEDLINE, EMBASE, Wiley’s Cochrane […]

Article: Personalized positive end-expiratory pressure during general anesthesia: go with the flow - Minerva Anestesiologica 2023 Feb 08 - Minerva Medica - Journals

Acute hypoxemic respiratory failure (ARF) is the most common cause of critical illness in oncologic patients. Despite significant advancements in survival of oncologic patients who develop critical illness, mortality rates in those requiring invasive mechanical ventilation have improved but remain high. Avoiding intubation is paramount to the management of oncologic patients with ARF. There are important differences between the oncologic patient with ARF compared to the general ICU population that likely underlie the increased mortality once intubated. Noninvasive oxygen modalities have been recognized as an important therapeutic approach to prevent intubation. Continuous low-flow oxygen therapy, noninvasive ventilation, and high-flow nasal cannula are the most commonly used noninvasive oxygen therapies in recent years. They have unique physiologic properties. The data surrounding their efficacy in the general ICU population and oncologic population has evolved over time reflecting the changes in the oncologic population. This chapter reviews the three different noninvasive oxygen modalities, their physiologic impact, and evidence surrounding their effectiveness.

Rationale: Diaphragm dysfunction worsens outcomes in mechanically ventilated patients, but the clinical impact of potentially preventable changes in diaphragm structure and function caused by mechanical ventilation is unknown. Objectives: To determine whether diaphragm atrophy developing during mechanical ventilation leads to prolonged ventilation. Methods: Diaphragm thickness was measured daily by ultrasound in adults requiring invasive mechanical ventilation; inspiratory effort was assessed by thickening fraction. The primary outcome was time to liberation from ventilation. Secondary outcomes included complications (reintubation, tracheostomy, prolonged ventilation, or death). Associations were adjusted for age, severity of illness, sepsis, sedation, neuromuscular blockade, and comorbidity. Measurements and Main Results: Of 211 patients enrolled, 191 had two or more diaphragm thickness measurements. Thickness decreased more than 10% in 78 patients (41%) by median Day 4 (interquartile range, 3–5). Development of decreased thickness was associated with a lower daily probability of liberation from ventilation (adjusted hazard ratio, 0.69; 95% confidence interval [CI], 0.54–0.87; per 10% decrease), prolonged ICU admission (adjusted duration ratio, 1.71; 95% CI, 1.29–2.27), and a higher risk of complications (adjusted odds ratio, 3.00; 95% CI, 1.34–6.72). Development of increased thickness (n = 47; 24%) also predicted prolonged ventilation (adjusted duration ratio, 1.38; 95% CI, 1.00–1.90). Decreasing thickness was related to abnormally low inspiratory effort; increasing thickness was related to excessive effort. Patients with thickening fraction between 15% and 30% (similar to breathing at rest) during the first 3 days had the shortest duration of ventilation. Conclusions: Diaphragm atrophy developing during mechanical ventilation strongly impacts clinical outcomes. Targeting an inspiratory effort level similar to that of healthy subjects at rest might accelerate liberation from ventilation.