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Objectives: Transcutaneous carbon dioxide (Tc co2 ) monitoring can noninvasively assess ventilation by estimating carbon dioxide ( CO2 ) levels in the blood. We aimed to evaluate the accuracy of Tc co2 monitoring in critically ill children by comparing it to the partial pressure of arterial carbon dioxide (Pa co2 ). In addition, we sought to determine the variation between Tc co2 and Pa co2 acceptable to clinicians to modify patient care and to determine which patient-level factors may affect the accuracy of Tc co2 measurements., Design: Retrospective observational cohort study., Setting: Single, quaternary care PICU from July 1, 2012, to August 1, 2020., Patients: Included participants were admitted to the PICU and received noninvasive ventilation support (i.e., continuous or bilevel positive airway pressure), conventional mechanical ventilation, or high-frequency oscillatory or percussive ventilation with Tc co2 measurements obtained within 15 minutes of Pa co2 measurement., Interventions: None., Measurements and Main Results: Three thousand four hundred seven paired arterial blood gas and Tc co2 measurements were obtained from 264 patients. Bland-Altman analysis revealed a bias of -4.4 mm Hg (95% CI, -27 to 18.3 mm Hg) for Tc co2 levels against Pa co2 levels on the first measurement pair for each patient, which fell within the acceptable range of ±5 mm Hg stated by surveyed clinicians, albeit with wide limits of agreement. The sensitivity and specificity of Tc co2 to diagnose hypercarbia were 93% and 71%, respectively. Vasoactive-Infusion Score (VIS), age, and self-identified Black/African American race confounded the relationship between Tc co2 with Pa co2 but percent fluid overload, weight-for-age, probe location, and severity of illness were not significantly associated with Tc co2 accuracy., Conclusions: Tc co2 monitoring may be a useful adjunct to monitor ventilation in children with respiratory failure, but providers must be aware of the limitations to its accuracy., Competing Interests: Dr. Coates received support for article research from The Doris Duke Foundation and The American Lung Association. Dr. Coates’ institution received funding from the Walder Foundation, the Doris Duke Foundation, the National Heart, Lung, and Blood Institute (R01 HL168672), and the American Lung Association; she received funding from Sobi, Triplett Woolf Garretson, LLC, and the Centers for Disease Control and Prevention; and she received support for article research from the Walder Foundation and the Doris Duke Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: We sought to evaluate the association between the carbon dioxide ( co2 ) ventilatory equivalent (VEq co2 = minute ventilation/volume of co2 produced per min), a marker of dead space that does not require a blood gas measurement, and mortality risk. We compared the strength of this association to that of physiologic dead space fraction (V D /V t = [Pa co2 -mixed-expired P co2 ]/Pa co2 ) as well as to other commonly used markers of dead space (i.e., the end-tidal alveolar dead space fraction [AVDSf = (Pa co2 -end-tidal P co2 )/Pa co2 ], and ventilatory ratio [VR = (minute ventilation × Pa co2 )/(age-adjusted predicted minute ventilation × 37.5)])., Design: Retrospective cohort data, 2017-2023., Setting: Quaternary PICU., Patients: One hundred thirty-one children with acute respiratory distress syndrome., Interventions: None., Measurements and Main Results: All dead space markers were calculated at the same 1-minute timepoint for each patient within the first 72 hours of using invasive mechanical ventilation. The 131 children had a median (interquartile range, IQR) age of 5.8 (IQR 1.4, 12.6) years, oxygenation index (OI) of 7.5 (IQR 4.6, 14.3), V D /V t of 0.47 (IQR 0.38, 0.61), and mortality was 17.6% (23/131). Higher VEq co2 ( p = 0.003), V D /V t ( p = 0.002), and VR ( p = 0.013) were all associated with greater odds of mortality in multivariable models adjusting for OI, immunosuppressive comorbidity, and overall severity of illness. We failed to identify an association between AVDSf and mortality in the multivariable modeling. Similarly, we also failed to identify an association between OI and mortality after controlling for any dead space marker in the modeling. For the 28-day ventilator-free days outcome, we failed to identify an association between V D /V t and the dead space markers in multivariable modeling, although OI was significant., Conclusions: VEq co2 performs similarly to V D /V t and other surrogate dead space markers, is independently associated with mortality risk, and may be a reasonable noninvasive surrogate for V D /V t ., Competing Interests: Dr. Khemani is supported by the National Institutes of Health (NIH)/the National Heart, Lung, and Blood Institute (NHLBI) R01 HL134666. Dr. Khemani is a consultant for Nihon-Kohden OrangeMed and Bayer. Nihon-Kohdon was not involved in this study and their module for volumetric capnography was not used in this study. Dr. Bhalla is supported by the NIH/NHLBI K23 HL153756. This work was also supported by grant UL1TR001855 from the NIH/National Center for Advancing Translational Science and support from the Department of Anesthesiology and Critical Care at Children’s Hospital Los Angeles. Drs. Bhalla and Khemani’s institutions received funding from the NHLBI. Dr. Bhalla disclosed personal stock ownership. Drs. Bhalla and, Khemani received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Many patients critically ill with COVID-19 develop acute respiratory distress syndrome (ARDS) necessitating mechanical ventilation and proning. Although proning is lifesaving, it has been linked to the occurrence of facial pressure injuries (PIs)., Objectives: To evaluate the incidence and use of prevention strategies and identify predictors of facial PIs in patients who received ventilator and proning treatments in COVID-designated intensive care units at 2 large quaternary medical centers in the Midwest., Method: This was a retrospective cohort study using data extracted from an electronic health record between October 2020 and February 2022. Demographics, clinical and care variables, and PI outcomes were analyzed to identify predictors of PI using logistic and Cox regression., Results: The cohort (N = 150) included patients from 2 units, unit a (n = 97) and unit b (n = 53) with a mean age of 60 years, with 68% identifying as male. Patients were vented for an average of 18 (SD, 16.2) days and proned for an average of 3 (SD, 2.5) days. Many (71%) died. Over half (56%) developed facial PI with a proning-exposure-adjusted incidence rate of 18.5%. Patients with PI were significantly different in several factors. Logistic regression showed predictors of PIs were duration of mechanical ventilation (in days; P = .02) and head turned (P = .01). Cox regression also identified head turn as predictive (P < .01), with Black/African American race as protective (P = .03)., Discussion: Critically ill patients with COVID-19 receiving ventilator and proning therapy developed facial PIs despite the use of recommended prevention practices. Further research on effective PI prevention strategies is needed., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Approximately 30% of people infected with COVID-19 require hospitalization, and 20% of them are admitted to an intensive care unit (ICU). Most of these patients experience symptoms of fatigue weeks post-ICU, so understanding the factors associated with fatigue in this population is crucial., Methods: Fifty-nine patients (38-78 yr) hospitalized in ICU for COVID-19 infection for 32 (6-80) d, including 23 (3-57) d of mechanical ventilation, visited the laboratory on two separate occasions. The first visit occurred 52 ± 15 d after discharge and was dedicated to questionnaires, blood sampling, and cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function and performance fatigability were performed in the second visit 7 ± 2 d later., Results: Using the FACIT-F questionnaire, 56% of patients were classified as fatigued. Fatigued patients had worse lung function score than non-fatigued (i.e., 2.9 ± 0.8 L vs 3.6 ± 0.8 L; 2.4 ± 0.7 L vs 3.0 ± 0.7 L for forced vital capacity and forced expiratory volume in 1 s, respectively), and forced vital capacity was identified as a predictor of being fatigued. Maximal voluntary activation was lower in fatigued patients than non-fatigued patients (82% ± 14% vs 91% ± 3%) and was the only neuromuscular variable that discriminated between fatigued and non-fatigued patients. Patient-reported outcomes also showed differences between fatigued and non-fatigued patients for sleep, physical activity, depression, and quality of life ( P < 0.05)., Conclusions: COVID-19 survivors showed altered respiratory function 4 to 8 wk after discharge, which was further deteriorated in fatigued patients. Fatigue was also associated with lower voluntary activation and patient-reported impairments (i.e., sleep satisfaction, quality of life, or depressive state). The present study reinforces the importance of exercise intervention and rehabilitation to counteract cardiorespiratory and neuromuscular impairments of COVID-19 patients admitted in ICU, especially individuals experiencing fatigue., (Copyright © 2024 by the American College of Sports Medicine.)

Background: Traumatic brain injury (TBI) is an expensive and common public health problem. Management of TBI oftentimes includes sedation to facilitate mechanical ventilation (MV) for airway protection. Dexmedetomidine has emerged as a potential candidate for improved patient outcomes when used for early sedation after TBI due to its potential modulation of autonomic dysfunction. We examined early sedation patterns, as well as the association of dexmedetomidine exposure with clinical and functional outcomes among mechanically ventilated patients with moderate-severe TBI (msTBI) in the United States., Methods: We conducted a retrospective cohort study using data from the Premier dataset and identified a cohort of critically ill adult patients with msTBI who required MV from January 2016 to June 2020. msTBI was defined by head-neck abbreviated injury scale (AIS) values of 3 (serious), 4 (severe), and 5 (critical). We described early continuous sedative utilization patterns. Using propensity-matched models, we examined the association of early dexmedetomidine exposure (within 2 days of intensive care unit [ICU] admission) with the primary outcome of hospital mortality and the following secondary outcomes: hospital length of stay (LOS), days on MV, vasopressor use after the first 2 days of admission, hemodialysis (HD) after the first 2 days of admission, hospital costs, and discharge disposition. All medications, treatments, and procedures were identified using date-stamped hospital charge codes., Results: The study population included 19,751 subjects who required MV within 2 days of ICU admission. The patients were majority male and white. From 2016 to 2020, the annual percent utilization of dexmedetomidine increased from 4.05% to 8.60%. After propensity score matching, early dexmedetomidine exposure was associated with reduced odds of hospital mortality (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.47-0.74; P < .0001), increased risk for liberation from MV (hazard ratio [HR], 1.20; 95% CI, 1.09-1.33; P = .0003), and reduced LOS (HR, 1.11; 95% CI, 1.01-1.22; P = .033). Exposure to early dexmedetomidine was not associated with odds of HD (OR, 1.14; 95% CI, 0.73-1.78; P = .56), vasopressor utilization (OR, 1.10; 95% CI, 0.78-1.55; P = .60), or increased hospital costs (relative cost ratio, 1.98; 95% CI, 0.93-1.03; P = .66)., Conclusions: Dexmedetomidine is being utilized increasingly as a sedative for mechanically ventilated patients with msTBI. Early dexmedetomidine exposure may lead to improved patient outcomes in this population., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Background: Impaired glymphatic clearance of cerebral metabolic products and fluids contribute to traumatic and ischemic brain edema and neurodegeneration in preclinical models. Glymphatic perivascular cerebrospinal fluid flow varies between anesthetics possibly due to changes in vasomotor tone and thereby in the dynamics of the periarterial cerebrospinal fluid (CSF)-containing space. To better understand the influence of anesthetics and carbon dioxide levels on CSF dynamics, this study examined the effect of periarterial size modulation on CSF distribution by changing blood carbon dioxide levels and anesthetic regimens with opposing vasomotor influences: vasoconstrictive ketamine-dexmedetomidine (K/DEX) and vasodilatory isoflurane., Methods: End-tidal carbon dioxide (ETco2) was modulated with either supplemental inhaled carbon dioxide to reach hypercapnia (Etco2, 80 mmHg) or hyperventilation (Etco2, 20 mmHg) in tracheostomized and anesthetized female rats. Distribution of intracisternally infused radiolabeled CSF tracer 111In-diethylamine pentaacetate was assessed for 86 min in (1) normoventilated (Etco2, 40 mmHg) K/DEX; (2) normoventilated isoflurane; (3) hypercapnic K/DEX; and (4) hyperventilated isoflurane groups using dynamic whole-body single-photon emission tomography. CSF volume changes were assessed with magnetic resonance imaging., Results: Under normoventilation, cortical CSF tracer perfusion, perivascular space size around middle cerebral arteries, and intracranial CSF volume were higher under K/DEX compared with isoflurane (cortical maximum percentage of injected dose ratio, 2.33 [95% CI, 1.35 to 4.04]; perivascular size ratio 2.20 [95% CI, 1.09 to 4.45]; and intracranial CSF volume ratio, 1.90 [95% CI, 1.33 to 2.71]). Under isoflurane, tracer was directed to systemic circulation. Under K/DEX, the intracranial tracer distribution and CSF volume were uninfluenced by hypercapnia compared with normoventilation. Intracranial CSF tracer distribution was unaffected by hyperventilation under isoflurane despite a 28% increase in CSF volume around middle cerebral arteries., Conclusions: K/DEX and isoflurane overrode carbon dioxide as a regulator of CSF flow. K/DEX could be used to preserve CSF space and dynamics in hypercapnia, whereas hyperventilation was insufficient to increase cerebral CSF perfusion under isoflurane., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Objectives: To evaluate the association between the pre-extubation sum of eye and motor components of the Glasgow Coma Score (GCS-EM) and odds of extubation failure in patients with acute brain injury being liberated from mechanical ventilation., Design: Secondary analysis of a prospective, multicenter observational study ( ClinicalTrials.gov identifier NCT03400904)., Setting: Sixty-three hospital sites worldwide, with patient recruitment from January 2018 to November 2020., Patients: One thousand one hundred fifty-two critically ill patients with acute brain injury, with a median age of 54 years, of whom 783 (68.0%) were male, 559 (48.5%) had traumatic brain injury, and 905 (78.6%) had a GCS-EM greater than 8 before extubation (scores range from 2 to 10)., Interventions: None., Measurements and Main Results: GCS-EM was computed in intubated patients on the day of extubation. The main outcome was extubation failure, defined as unplanned reintubation within 5 days of extubation. Analyses used multilevel logistic regression with adjustment for patient characteristics and a random intercept for hospital site. In the primary analysis, GCS-EM was not associated with extubation failure (odds ratio, 1.07 per additional point; 95% CI, 0.87-1.31). Findings were consistent in sensitivity analyses that: 1) used different adjustment covariates, 2) included a verbal estimate to derive an overall GCS, 3) accounted for missing data, 4) considered a 2-day time interval to define extubation failure, 5) accounted for competing risks, and 6) used a propensity score-based model. There was no association between GCS-EM and extubation outcome in subgroups defined by brain injury diagnosis or age., Conclusions: In this large, contemporary, multicenter cohort of patients with acute brain injury, we found no association between the GCS-EM and odds of extubation failure. However, few patients had a pre-extubation GCS-EM less than or equal to 8, and the possibility of a true prognostic association in patients with low scores is not excluded., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interests., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: Volumetric capnography depicts volumetric capnograms [ie, the plot of expired carbon dioxide (CO 2 ) over the tidal volume]. This bench study aimed to determine the reliability, accuracy, and precision of a novel infant simulator for volumetric capnography. This simulator would be clinically valuable for teaching purposes because it reflects the entire cardiopulmonary physiology within 1 breath., Methods: An infant lung simulator was fed with CO 2 supplied by a mass flow controller (VCO 2-IN ) and ventilated using standard settings. A volumetric capnograph was placed between the endotracheal tube and the ventilatory circuit. We simulated ventilated babies of different body weights (2, 2.5, 3, and 5 kg) with a VCO 2 ranging from 12 to 30 mL/min. The correlation coefficient ( r2 ), bias, coefficient of variation (CV = SD/ x × 100), and precision (2 × CV) between the VCO 2-IN and the elimination of CO 2 recorded by the capnograph (VCO 2-OUT ) were calculated. The quality of the capnogram's waveforms was compared with real ones belonging to anesthetized infants using an 8-point scoring system, where 6 points or greater meant that the simulated capnogram showed good, 5 to 3 points acceptable, and less than 3 points an unacceptable shape., Results: The correlation between VCO 2-IN and VCO 2-OUT was r2 = 0.9953 ( P < 0.001), with a bias of 0.16 (95% confidence intervals from 0.12 to 0.20) mL/min. The CV was 5% or less and the precision was 10% or less. All simulated capnograms showed similar shapes compared with real babies, scoring 6 points for 3 kg and 6.5 points for 2-, 2.5-, and 5-kg babies., Conclusions: The simulator of volumetric capnograms was reliable, accurate, and precise for simulating the CO 2 kinetics of ventilated infants., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Society for Simulation in Healthcare.)

Objectives: Multicenter studies reporting outcomes following tracheostomy in children with congenital heart disease are limited, particularly in patients with single ventricle physiology. We aimed to describe clinical characteristics and outcomes in a multicenter cohort of patients with single ventricle physiology who underwent tracheostomy before Fontan operation., Design: Multicenter retrospective cohort study., Setting: Twenty-one tertiary care pediatric institutions participating in the Collaborative Research from the Pediatric Cardiac Intensive Care Society., Patients: We reviewed 99 children with single ventricle physiology who underwent tracheostomy before the Fontan operation at 21 institutions participating in Collaborative Research from the Pediatric Cardiac Intensive Care Society between January 2010 and December 2020, with follow-up through December 31, 2021., Interventions: None., Measurements and Main Results: Death occurred in 51 of 99 patients (52%). Cox proportional hazard analysis was performed to determine factors associated with death after tracheostomy. Results are presented as hazard ratio (HR) with 95% CIs. Nonrespiratory indication(s) for tracheostomy (HR, 2.21; 95% CI, 1.14-4.32) and number of weeks receiving mechanical ventilation before tracheostomy (HR, 1.06; 95% CI, 1.02-1.11) were independently associated with greater hazard of death. In contrast, diagnosis of tricuspid atresia or Ebstein's anomaly was associated with less hazard of death (HR, 0.16; 95% CI, 0.04-0.69). Favorable outcome, defined as survival to Fontan operation or decannulation while awaiting Fontan operation with viable cardiopulmonary physiology, occurred in 29 of 99 patients (29%). Median duration of mechanical ventilation before tracheostomy was shorter in patients who survived to favorable outcome (6.1 vs. 12.1 wk; p < 0.001), and only one of 16 patients with neurologic indications for tracheostomy and 0 of ten patients with cardiac indications for tracheostomy survived to favorable outcome., Conclusions: For children with single ventricle physiology who undergo tracheostomy, mortality risk is high and should be carefully considered when discussing tracheostomy as an option for these children. Favorable outcomes are possible, although thoughtful attention to patient selection and tracheostomy timing are likely necessary to achieve this goal., Competing Interests: Dr. Mastropietro received funding from Telan, Meltz, Wallace, and Eide Law Firm, and Bioporto. Dr. Werho received funding from University of California San Diego; his institution received funding from the American Heart Association; and he disclosed that he is a board member of the Pediatric Cardiac Intensive Care Society and the Pediatric Cardiac Critical Care Consortium. Dr. Yates received funding from Alexion Pharmaceuticals. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Millettia pachycarpa Benth, rich in rotenone, can disrupt the mitochondrial electron transport chain. Ingestion may cause respiratory and central nervous system depression, and in severe cases, lead to death. This is the first detailed clinical case report of M. pachycarpa Benth poisoning, aiming to help systematization of diagnosis and treatment., Patient Concerns: An elderly male who lost consciousness for 3 hours after consuming the fruit of M. pachycarpa Benth. Arterial blood gas analysis indicated a significant decrease in pH, a sharp increase in lactate levels, and elevated CO2 partial pressure with normal O2 partial pressure., Diagnosis: The patient was diagnosed with food intoxication by M. pachycarpa Benth, concomitant with aspiration pneumonia and distributive shock., Interventions: The patient was given continuous renal replacement therapy (CRRT) and invasive mechanical ventilation., Outcomes: The patient was successfully discharged after 5 days of hospitalization. Follow-up after 2 weeks showed no significant discomfort., Conclusion: Isolated CO2 retention without hypoxemia, significantly reduced pH, and markedly elevated lactate levels strongly suggest poisoning by M. pachycarpa Benth. CRRT and invasive mechanical ventilation are beneficial for patients. Early implementation of CRRT to remove toxins and early initiation of assisted ventilation to improve respiratory failure are recommended upon suspicion of the disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Lack of proper eye care (EC) for mechanically ventilated patients can lead to serious ocular complications. Objective of this study is to develop and validate eyes care bundle for mechanically ventilated patients. A Delphi design study was conducted between March and May 2021. The Content Validity Index (CVI) was used to calculate the degree of agreement among the experts to analyze the bundle. Content validity was determined by 5 experts using a 4-point Likert scale. They evaluated the items in terms of the following: 1 = "irrelevant," 2 = "somewhat relevant if the phrasing is profoundly adjusted," 3 = "relevant with some adjustment," and 4 = "very relevant." The CVI was applied, and the accepted value was ≥0.50. The validation of EC bundle was conducted through 3 rounds after developed it based on the evaluated research evidence. The items were reviewed for content and face validity. The bundle was validated with 5 items with a total CVI of 0.96, a face validity of 1, and a Scale-Level Content Validity Index/Universal Agreement calculation method value of 0.8. This bundle can help critical care nurses, doctors, academics, and students assess and provide standard EC for mechanically ventilated patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Introduction : Early-onset pneumonia (EOP) occurs in around 50% of critically ill patients with out-of-hospital cardiac arrest (OHCA) and is associated with increased morbidity. Prompt diagnosis of EOP in these patients is difficult because of targeted temperature management and the postcardiac arrest syndrome. We hypothesized that an algorithm for proactive screening of EOP would improve patient outcomes. Methods : We conducted a single-center observational study comparing the outcomes of mechanically ventilated adult patients with OHCA, before (study period 1) and after (study period 2) implementation of an algorithm for proactive diagnosis of EOP, including an early distal pulmonary specimen. An inverse probability treatment weighted multivariable regression was performed to identify independent parameters associated with duration of mechanical ventilation. A subgroup analysis was conducted in patients alive on day 5 after intensive care unit admission. Results : Over the 4-year study period, 190 patients (99 and 91 for study periods 1 and 2, respectively) were enrolled. The overall incidence of EOP was 57.4% and was similar between both study periods. Although there was no difference in the time interval to antibiotic initiation, study period 2 was independently associated with higher SpO 2 /FiO 2 ratios on days 3 and 4. We also observed a decrease in mechanical ventilation time in study period 2 (4.5 [1-11.3] vs. 3 [2-5.8] days; P = 0.07), and this reached statistical significance in the subgroup analysis of patients alive at day 5 (10 [5-17] vs. 5 [3-9] days, P = 0.01). Conclusion: In critically ill patients with OHCA, proactive diagnosis of EOP was not associated with a significant change in the time to antibiotic initiation. Further research is warranted to better define optimal diagnosis and management of EOP in this setting., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Background: Artificial airways are essential in various clinical settings to maintain a patient's airway and provide necessary support for ventilation and oxygenation. These devices are commonly temporary and come in several types, each serving specific purposes. Understanding the indications, types, and proper care of artificial airways is crucial for health care professionals to ensure patients receive optimal care and prevent complications., Objective: This article aims to review the indications for using artificial airways and discuss the most commonly used types, including supraglottic airway devices, endotracheal tubes, tracheostomy tubes, and laryngectomy tubes. It also provides insights into the procedures involved in intubation and percutaneous tracheostomy and offers guidance on patient management, emphasizing assessment, oral care, suctioning, and humidification for patients with these airway devices., Conclusion: This article underscores the significance of understanding artificial airways, not just as a set of skills but as a commitment to patient welfare. Health care professionals who master the knowledge and care of these devices can significantly contribute to their patients' well-being and quality of life., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Dr. Anesi is supported by the National Heart, Lung, and Blood Institute (grant K23HL161353), the Center for Disease Control and Prevention Foundation, the Society of Critical Care Medicine, and the University of Pennsylvania Perelman School of Medicine Thomas B. McCabe and Jeannette E. Laws McCabe Fund and Leonard Davis Institute of Health Economics; he received payments from UptoDate and various law firms; he disclosed that his spouse is employed by the U.S. Food and Drug Administration; he disclosed discussion of the off-label product use of nonconventional ventilators during the COVID-19 pandemic. Dr. Agarwal has disclosed that she does not have any potential conflicts of interest.

Aim: The aim of this study was to determine the best clinical predictors of acute heart failure needing mechanical ventilation (MV) in the first 48 h of evolution of patients admitted because of acute coronary syndrome (ACS)., Methods: We analyzed a cohort of patients admitted for ACS between February 2017 and February 2018. A pulmonary ultrasound was performed on admission and was considered positive (PE+) when there were three or more B-lines in two quadrants or more of each hemithorax. It was compared with N-terminal pro-B-type natriuretic peptide (NT-proBNP), peak troponin T-us value GRACE (Global Registry of Acute Coronary Events), CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology and American Heart Association guidelines - Bleeding Score), CACS (Canada Acute Coronary Syndrome risk score), and HAMIOT (Heart Failure after Acute Myocardial Infarction with Optimal Treatment score) scores, shock index, ejection fraction, chest X-ray, and Killip class at admission as predictors of MV in the first 48 h of admission., Results: A total of 119 patients were included: 54.6% with ST elevation and 45.4% without ST elevation. Twelve patients (10.1%) required MV in the first 48 h of evolution. The sensitivity of PE+ was 100% (73.5-100%), specificity 91.6% (84.6-96.1%), and area under the curve was 0.96 (0.93-0.96). The sensitivity of an NT-proBNP value more than 3647 was 88.9% (51.9-99.7%), specificity 92.1% (84.5-96.8%), and area under the curve was 0.905 (0.793-1). The κ statistic between both predictors was 0.579. All the other scores were significantly worse than PE + ., Conclusion: Lung ultrasound and a high NT-proBNP (3647 ng/L in our series) on admission are the best predictors of acute heart failure needing MV in the first 48 h of ACS. The agreement between both tests was only moderate., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

To investigate effectiveness of the ABCDEF bundle to manage and prevent delirium., Background: ICU delirium is a common hospital problem that 80% of critically ill patients in the ICU experience. The ABCDEF bundle is one of the tools that included in Delirium guidelines to manage critically ill patients., Research Design: Pre- and post intervention a quasi-experimental design was utilized in the present study., Setting: This study was conducted in the intensive care units of Assiut University Hospital., Methods: A total of 60 mechanically ventilated patients were recruited using inclusion and exclusion criteria. The ABCDEF bundle was implemented every day for the first 7 days of ICU admission, and patient sedation and delirium status were assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Sedation instrument measures were utilized in data collection., Results: Significant differences were found in the incidence of delirium: 20% in the study group versus 70% in the control group. The increased mean of days without delirium ICU stay was 4.6333 in the study group and 1.1000 in the control group, with P value = .001., Conclusion: The mechanically ventilated patients exposed to the implementation of the ABCDE bundle experienced fewer delirium signs than before the ABCDE bundle was implemented., Competing Interests: The author has no conflicts of interest in the manuscript, including financial, consultant, institutional, and other relationships that might lead to bias or a conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: This review aims to explore the latest evidence on long-term outcomes in patients admitted to the ICU because of acute respiratory failure (ARF)., Recent Findings: As the survival rate of critically ill patients with acute respiratory failure improves, long-term mortality and disability still influence the quality of life of survivors and their caregivers. Patients admitted to the ICU because of ARF are at risk of developing the postintensive care syndrome, which presents with physical, cognitive and mental symptoms, all of which may impair their quality of life. Caregivers seem to be affected as well, which may lead to intergenerational trauma. The need for more care, including prone positioning, invasive support (e.g. mechanical ventilation, ECMO) and deep sedation are probably adjunctive risk factors for poor long-term outcomes., Summary: There is not much data on the long-term outcomes of patients who have survived ARF. More follow-up studies should be conducted, especially in centers providing higher levels of costly care (e.g. ECMO). Randomized controlled trials on interventions for ARF should include patient-centered long-term outcomes in addition to mortality rates. The high mortality rates associated with ARF mandate collaboration among multiple centers to achieve an adequate sample size for studying the long-term outcomes of survivors., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: This review explores the similarities and differences between coronavirus disease 2019 (COVID-19)-related and non-COVID-related nosocomial pneumonia, particularly hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). It critically assesses the etiology, prevalence, and mortality among hospitalized patients, emphasizing the burden of these infections during the period before and after the severe acute respiratory syndrome coronavirus 2 pandemic., Recent Findings: Recent studies highlight an increase in nosocomial infections during the COVID-19 pandemic, with a significant rise in cases involving severe bacterial and fungal superinfections among mechanically ventilated patients. These infections include a higher incidence of multidrug-resistant organisms (MDROs), complicating treatment and recovery. Notably, COVID-19 patients have shown a higher prevalence of VAP than those with influenza or other respiratory viruses, influenced by extended mechanical ventilation and immunosuppressive treatments like corticosteroids., Summary: The findings suggest that COVID-19 has exacerbated the frequency and severity of nosocomial infections, particularly VAP. These complications not only extend hospital stays and increase healthcare costs but also lead to higher morbidity and mortality rates. Understanding these patterns is crucial for developing targeted preventive and therapeutic strategies to manage and mitigate nosocomial infections during regular or pandemic care., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To validate a mathematical model using porous media theory for alveolar CO2 determination in ventilated patients., Design: Mathematical modeling study with prospective clinical validation to simulate CO2 exchange from bloodstream to airway entrance., Setting: ICU., Patients: Thirteen critically ill patients without chronic or acute lung disease., Interventions: None., Measurements and Main Results: Model outcomes compared with patient data showed correlations for end-tidal CO2 (EtCO 2 ), area under the CO2 curve, and Pa CO2 of 0.918, 0.954, and 0.995. Determination coefficients ( R2 ) were 0.843, 0.910, and 0.990, indicating precision and predictive power., Conclusions: The mathematical model shows potential in pulmonary critical care. Although promising, practical application demands further validation, clinician training, and patient-specific adjustments. The path to clinical use will be iterative, involving validation and education., Competing Interests: Drs. Jiménez-Posada, Palacio Sánchez, Montagut Ferizzola, and Maya López received support for article research from Fondo de Investigación en Salud, convocatoria 807-2018 Colciencias, Colombia (project 133380764110, contract 801-2018). Dr. Ardila Villegas has disclosed that he does not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Background: A noninvasive and accurate method of determining fluid responsiveness in ventilated patients would help to mitigate unnecessary fluid administration. Although carotid ultrasound has been previously studied for this purpose, several studies have recently been published. We performed an updated systematic review and meta-analysis to evaluate the accuracy of carotid ultrasound as a tool to predict fluid responsiveness in ventilated patients., Methods: Studies eligible for review investigated the accuracy of carotid ultrasound parameters in predicting fluid responsiveness in ventilated patients, using sensitivity and specificity as markers of diagnostic accuracy (International Prospective Register of Systematic Reviews [PROSPERO] CRD42022380284). All included studies had to use an independent method of determining cardiac output and exclude spontaneously ventilated patients. Six bibliographic databases and 2 trial registries were searched. Medline, Embase, Emcare, APA PsycInfo, CINAHL, and the Cochrane Library were searched on November 4, 2022. Clinicaltrials.gov and Australian New Zealand Clinical Trials Registry were searched on February 24, 2023. Results were pooled, meta-analysis was conducted where possible, and hierarchical summary receiver operating characteristic models were used to compare carotid ultrasound parameters. Bias and evidence quality were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines., Results: Thirteen prospective clinical studies were included (n = 648 patients), representing 677 deliveries of volume expansion, with 378 episodes of fluid responsiveness (58.3%). A meta-analysis of change in carotid Doppler peak velocity (∆CDPV) yielded a sensitivity of 0.79 (95% confidence interval [CI], 0.74-0.84) and a specificity of 0.85 (95% CI, 0.76-0.90). Risk of bias relating to recruitment methodology, the independence of index testing to reference standards and exclusionary clinical criteria were evaluated. Overall quality of evidence was low. Study design heterogeneity, including a lack of clear parameter cutoffs, limited the generalizability of our results., Conclusions: In this meta-analysis, we found that existing literature supports the ability of carotid ultrasound to predict fluid responsiveness in mechanically ventilated adults. ∆CDPV may be an accurate carotid parameter in certain contexts. Further high-quality studies with more homogenous designs are needed to further validate this technology., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Objectives: Critically ill patients with tuberculosis carry high mortality. Identification of factors associated with mortality in critically ill tuberculosis patients may enable focused treatment., Data Sources: An extensive literature search of PubMed (MEDLINE), Embase, the Cochrane Library, and Google Scholar was performed using Medical Subject Headings terms "tuberculosis," "critical care," "critical care outcome," and "ICU." We aimed to identify factors affecting mortality in critically ill tuberculosis patients., Study Selection: All the studies comparing factors affecting mortality between survivors and nonsurvivors in critically ill tuberculosis patients were included. The database search yielded a total of 3017 records, of which 17 studies were included in the meta-analysis., Data Extraction: Data were collected including the name of the author, year and country of publication, duration of the study, number of patients studied, type of tuberculosis, patient demography, smoking history, laboratory parameters, comorbidities, the requirement for mechanical ventilation, duration of ventilation, ICU and hospital length of stay (LOS), type of lung involvement, complications, and outcomes., Data Synthesis: The major factors that contributed to mortality in critically ill tuberculosis patients were age, platelet count, albumin, C-reactive protein (CRP), the requirement and duration of invasive mechanical ventilation, Pa o2 /F io2 ratio, presence of acute respiratory distress syndrome, shock, hospital-acquired infections, renal replacement therapy, and ICU and hospital LOS., Conclusions: Patient age, platelet count, albumin and CRP levels, the requirement and duration of invasive mechanical ventilation, Pa o2 /F io2 ratio, hospital-acquired infections, renal replacement therapy, and ICU LOS were variables associated with mortality., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Abstract: Introduction: The global demand for intensive care has risen, given its effectiveness in lowering mortality rates. Mechanical ventilation (MV) is integral to intensive care but introduces risks such as ventilator-associated complications. Ethiopia experiences a high intensive care unit (ICU) mortality rate. Objective: This systematic review and meta-analysis aim to comprehensively synthesize evidence on the mortality of adults undergoing MV in Ethiopia and identify associated factors. Methods: The study extensively searched databases and gray literature for research on MV outcomes, trends, and associated factors in adult ICUs. Adhering to the 2020 PRISMA checklist, a systematic review and meta-analysis sought to establish the mortality rate and key determinants among adult ICU patients on MV. The search incorporated keywords and MeSH terms, excluding studies with unsound methodologies or missing data. Data extraction, quality assessment, and analysis followed established protocols, including the JBI tool for methodological quality evaluation. STATA version 17.0 facilitated analysis, assessing heterogeneity, publication bias, and performing sensitivity and meta-regression analyses. Results: The pooled mortality rate among adult ICU patients undergoing MV was 48.61% (95% CI: 40.82, 56.40%). Significant mortality-contributing factors included medical diagnosis, Glasgow Coma Scale score, sepsis/septic shock, sedation use, multiple-organ dysfunction syndrome, and cardiovascular disease. Although some pooled odds ratios seemed insignificant, closer examination revealed significant associations in individual studies. Conclusion : The study underscores the urgent need for further research, improved ICU infrastructure, and healthcare personnel training in Ethiopia to enhance outcomes for mechanically ventilated patients. Identified factors offer valuable insights for targeted interventions, guiding tailored treatment strategies to reduce mortality. This study contributes to understanding mortality and associated factors in MV patients, informing initiatives to improve critical care outcomes in Ethiopia., Competing Interests: Author conflict of interest statement: The authors declare that there is no conflict of interest regarding the publication of this article, "Prevalence of Mortality and Associated Factors Among ICU-Admitted Adult Patients with Mechanical Ventilation in Ethiopia: A Systematic Review and Meta-Analysis." The research was conducted objectively, and the authors have no financial or personal relationships that could influence or bias the findings and conclusions presented in this manuscript. This work was carried out with the sole purpose of contributing to the scientific understanding of mortality and associated factors in mechanically ventilated patients in Ethiopian ICUs. The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Emerging evidence suggests prolonged use of noninvasive respiratory support may increase mortality of patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome who require extracorporeal membrane oxygenation (ECMO). Using a database of adults receiving ECMO for COVID-19, we calculated survival curves and multivariable Cox regression to determine the risk of death associated with pre-ECMO use of high-flow nasal oxygen (HFNO), noninvasive ventilation (NIV), and invasive mechanical ventilation (IMV) days. We investigated the performance of a novel variable, advanced respiratory support days (composite of HFNO, NIV, and IMV days), on Respiratory ECMO Survival Prediction (RESP) score. Subjects (N = 146) with increasing advanced respiratory support days (<5, 5-9, and ≥10) had a stepwise increase in 90 day mortality (32.2%, 57.7%, and 75.4%, respectively; p = 0.002). Ninety-day mortality was significantly higher in subjects (N = 121) receiving NIV >4 days (81.8% vs. 52.4%, p < 0.001). Each additional pre-ECMO advanced respiratory support day increased the odds of right ventricular failure (odds ratio [OR]: 1.066, 95% confidence interval [CI]: 1.002-1.135) and in-hospital mortality (1.17, 95% CI: 1.08-1.27). Substituting advanced respiratory support days for IMV days improved RESP score mortality prediction (area under the curve (AUC) or: 0.64 vs. 0.71). Pre-ECMO advanced respiratory support days were associated with increased 90 day mortality compared with IMV days alone. Adjusting the RESP score for advanced respiratory support days improved mortality prediction., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Objectives: The purpose of the study is to examine the outcomes of care delivered at the pediatric trauma center (PTC) in severely injured children who were intubated, mechanically ventilated, and underwent tracheostomy., Methods: The study data were obtained from the Trauma Quality Improvement Program database for the calendar years 2017 to 2019. All children aged ≤17 years who sustained severe injury, required intubation and mechanical ventilation for more than 96 hours, and underwent tracheostomy were included in the study. Patients' characteristics, injury severity, and outcomes were compared between the care provided at the PTCs (level I or level II) and nonpediatric trauma centers (NPTCs). The propensity score matching methodology was used to perform the analysis. All P values are 2-sided, and a P value of <0.0.5 is considered statistically significant., Results: Of 2164 patients who were qualified for the study, 1288 (59%) of the patients were treated at PTCs, and 876 (40.5%) of the patients were treated at NPTCs. Propensity matching created 876 pairs of patients. There were no significant differences found between the 2 groups on patients' characteristics except for age. Patients who were treated at PTCs had a median age of 14 (10-16) versus 15 (11-17) years ( P < 0.001) when compared with care provided at NPTCs. A longer hospital stay was found in the PTC group when compared with the NPTC group (24 [23, 25] vs 22 [21, 24], P = 0.008). Patients who were treated at PTC were found to have significantly less sepsis occurrence (0.9% vs 2.2%), and a higher proportion of patients were discharged home without needing additional support (26.2% vs 18.5%)., Conclusions: Care at the PTC was associated with a lower occurrence of sepsis complications. A higher number of patients were discharged home without additional services when the care was provided at PTC., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine early sedation patterns, as well as the association of dexmedetomidine exposure, with clinical and functional outcomes among mechanically ventilated patients with moderate-severe traumatic brain injury (msTBI)., Design: Retrospective cohort study with prospectively collected data., Setting: Eighteen Level-1 Trauma Centers, United States., Patients: Adult (age > 17) patients with msTBI (as defined by Glasgow Coma Scale < 13) who required mechanical ventilation from the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study., Interventions: None., Measurements and Main Results: Using propensity-weighted models, we examined the association of early dexmedetomidine exposure (within the first 5 d of ICU admission) with the primary outcome of 6-month Glasgow Outcomes Scale Extended (GOS-E) and the following secondary outcomes: length of hospital stay, hospital mortality, 6-month Disability Rating Scale (DRS), and 6-month mortality. The study population included 352 subjects who required mechanical ventilation within 24 hours of admission. The initial sedative medication was propofol for 240 patients (68%), midazolam for 59 patients (17%), ketamine for 6 patients (2%), dexmedetomidine for 3 patients (1%), and 43 patients (12%) never received continuous sedation. Early dexmedetomidine was administered in 77 of the patients (22%), usually as a second-line agent. Compared with unexposed patients, early dexmedetomidine exposure was not associated with better 6-month GOS-E (weighted odds ratio [OR] = 1.48; 95% CI, 0.98-2.25). Early dexmedetomidine exposure was associated with lower DRS (weighted OR = -3.04; 95% CI, -5.88 to -0.21). In patients requiring ICP monitoring within the first 24 hours of admission, early dexmedetomidine exposure was associated with higher 6-month GOS-E score (OR 2.17; 95% CI, 1.24-3.80), lower DRS score (adjusted mean difference, -5.81; 95% CI, -9.38 to 2.25), and reduced length of hospital stay (hazard ratio = 1.50; 95% CI, 1.02-2.20)., Conclusion: Variation exists in early sedation choice among mechanically ventilated patients with msTBI. Early dexmedetomidine exposure was not associated with improved 6-month functional outcomes in the entire population, although may have clinical benefit in patients with indications for ICP monitoring., Competing Interests: Dr. Temkin’s institution received funding from the National Institute of Neurological Disorders and Stroke (NINDS), Abbott, and the U.S. Federal Government; she received funding from Bristol-Myers-Squibb, the Medical College of Wisconsin, Neurotrauma Sciences, and Novartis. Drs. Temkin and Markowitz’s institutions received funding from the U.S. Department of Defense (DoD). Drs. Temkin, Komisarow, Manley, Vavilala, and Krishnamoorthy received support for article research from the National Institutes of Health. Dr. Manley’s institution received funding from NINDS (U01NS086090). Dr. Markowitz received support for article research from the U.S. DoD. Dr. Krishnamoorthy’s institution received funding from NINDS (K23NS109274). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: Profound dengue shock syndrome (DSS) complicated by severe respiratory failure necessitating mechanical ventilation (MV) accounts for high case fatality rates among PICU-admitted patients. A major challenge to management is the assessment of intravascular volume, which can be hampered by severe plasma leakage and the use of MV., Design: Retrospective cohort, from 2013 to 2021., Patients: Sixty-seven children with profound DSS supported by MV, some of whom underwent bedside point-of-care ultrasound (POCUS) for assessment and monitoring of hemodynamics and fluid administration., Setting: PICU of the tertiary Children's Hospital No. 2 in Vietnam., Interventions: None., Measurements and Main Results: We analyzed data clinical and laboratory data during PICU stay. In particular, during use of MV (i.e., at times 0-, 6-, and 24-hr after commencement) and fluid resuscitation. The primary study outcome was 28-day in-hospital mortality, and the secondary outcomes were associations with changes in hemodynamics, blood lactate, and vasoactive-inotrope score (VIS). Patients had a median age of 7 years (interquartile range, 4-9). Use of POCUS during fluid management (39/67), as opposed to not using (28/67), was associated with lower mortality (6/39 [15%] vs. 18/28 [64%]; difference 49 % [95% CI, 28-70%], p < 0.001). Use of POCUS was associated with lower odds of death (adjusted odds ratio 0.17 [95% CI, 0.04-0.76], p = 0.02). The utilization of POCUS, versus not, was associated with greater use of resuscitation fluid, and reductions in VIS and pediatric logistic organ dysfunction (PELOD-2) score at 24 hours after MV and PICU discharge., Conclusions: In our experience of pediatric patients with profound DSS and undergoing MV (2013-2021), POCUS use was associated with lower odds of death, a higher volume of resuscitation fluid, and improvements in the blood lactate levels, VIS, and PELOD-2 score., Competing Interests: Drs. T.T. Nguyen, T.L. Vo, Nguyen , D.T. Tran, Đoan, Pham, Mai, Q.X.T. Nguyen, T.K. Nguyen, and T.T.K. Nguyen disclosed the study was funded by Kim Oanh Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: Sedation and analgesia for infants and children requiring mechanical ventilation in the PICU is uniquely challenging due to the wide spectrum of ages, developmental stages, and pathophysiological processes encountered. Studies evaluating the safety and efficacy of sedative and analgesic management in pediatric patients have used heterogeneous methodologies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) IV hosted a series of multidisciplinary meetings to establish consensus statements for future clinical study design and implementation as a guide for investigators studying PICU sedation and analgesia., Design: Twenty-five key elements framed as consensus statements were developed in five domains: study design, enrollment, protocol, outcomes and measurement instruments, and future directions., Setting: A virtual meeting was held on March 2-3, 2022, followed by an in-person meeting in Washington, DC, on June 15-16, 2022. Subsequent iterative online meetings were held to achieve consensus., Subjects: Fifty-one multidisciplinary, international participants from academia, industry, the U.S. Food and Drug Administration, and family members of PICU patients attended the virtual and in-person meetings. Participants were invited based on their background and experience., Interventions: None., Measurements and Main Results: Common themes throughout the SCEPTER IV consensus statements included using coordinated multidisciplinary and interprofessional teams to ensure culturally appropriate study design and diverse patient enrollment, obtaining input from PICU survivors and their families, engaging community members, and using developmentally appropriate and validated instruments for assessments of sedation, pain, iatrogenic withdrawal, and ICU delirium., Conclusions: These SCEPTER IV consensus statements are comprehensive and may assist investigators in the design, enrollment, implementation, and dissemination of studies involving sedation and analgesia of PICU patients requiring mechanical ventilation. Implementation may strengthen the rigor and reproducibility of research studies on PICU sedation and analgesia and facilitate the synthesis of evidence across studies to improve the safety and quality of care for PICU patients., Competing Interests: The views expressed in this article are those of the authors, none of whom have financial conflicts of interest specifically related to the issues discussed in this article, and no official endorsement by the U.S. Food and Drug Administration or those entities that provided grants to support the activities of the Analgesic, Anesthetic, Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership. Drs. Lee, Jackson, Biagas, Houck, Smith, Ward, Zimmerman, and Huang received funding from Analgesic, Anesthetic, Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION). Dr. Beers disclosed that she is part-time ad hoc faculty at the University of Pittsburgh. Dr. Berkenbosch received funding from Innovation Consulting; he disclosed that he is a consulting bureau member for Medtronic; and he received support for article research from ACTTION-Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER)-public-private consortium with the U.S. Food and Drug Administration (FDA). Dr. Dworkin’s institution received funding from the FDA; he received funding from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, Beckley, Biogen, Biohaven, Biosplice, Boston Scientific, Braeburn, Cardialen, Centrexion, Chiesi, Chromocell, Clexio, Collegium, CombiGene, Confo, Decibel, Editas, Eli Lilly, Endo, Ethismos (equity), Eupraxia, Exicure, GlaxoSmithKline, Glenmark, Gloriana, Hope, Kriya, Lotus, Mainstay, Merck, Mind Medicine (also equity), Neumentum, Neurana, NeuroBo, Novaremed, Novartis, OliPass, Orion, Oxford Cannabinoid Technologies, Pfizer, Q-State, Reckitt Benckiser, Regenacy (also equity), Rho, Sangamo, Sanifit, Scilex, Semnur, SIMR Biotech, Sinfonia, SK Biopharmaceuticals, Sollis, SPM Therapeutics, SPRIM Health, Teva, Theranexus, Vertex, Vizuri, and WCG. Dr. Smith received funding for an ongoing sedation trial in mechanically ventilated pediatric patients from the National Heart, Lung, and Blood Institute. Dr. Ward received funding from the Maine State Board of Education. Dr. Zimmerman’s institution received funding from the National Institutes of Health (NIH), the FDA, and the Biogen Foundation. Dr. Horvat’s institution received funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute of Neurological Disorders and Stroke. Drs. Horvat and Sun received support for article research from the NIH. Drs. Salorio and Slomine received funding from the Innovations Consulting Group. Dr. Slater’s institution received funding from Wellcome and the Annabels Foundation; she received funding from Reckitt; she received support for article research from Wellcome Trust/Charity Open Access Fund. Dr. Slomine received funding from Cambridge University Press and Goodell, Devries, Leech & Dann, LLP. Dr. West disclosed that she is employed at Georgia Tech and that she is the President of International Children’s Advisory Network. Dr. Wypij received funding from SCEPTER IV. Dr. Yeates’ institution received funding from the Canadian Institutes of Health Research; he received funding from Guilford Publications and the American Psychological Association. Dr. Sun received funding from McGraw Hill; she disclosed that she is Co-Editor-in-Chief of Anesthesiology UpToDate. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: To summarize the effectiveness of implementation strategies for ICU execution of recommendations from the 2013 Pain, Agitation/Sedation, Delirium (PAD) or 2018 PAD, Immobility, Sleep Disruption (PADIS) guidelines., Data Sources: PubMed, CINAHL, Scopus, and Web of Science were searched from January 2012 to August 2023. The protocol was registered with PROSPERO (CRD42020175268)., Study Selection: Articles were included if: 1) design was randomized or cohort, 2) adult population evaluated, 3) employed recommendations from greater than or equal to two PAD/PADIS domains, and 4) evaluated greater than or equal to 1 of the following outcome(s): short-term mortality, delirium occurrence, mechanical ventilation (MV) duration, or ICU length of stay (LOS)., Data Extraction: Two authors independently reviewed articles for eligibility, number of PAD/PADIS domains, quality according to National Heart, Lung, and Blood Institute assessment tools, implementation strategy use (including Assess, prevent, and manage pain; Both SAT and SBT; Choice of analgesia and sedation; Delirium: assess, prevent, and manage; Early mobility and exercise; Family engagement and empowerment [ABCDEF] bundle) by Cochrane Effective Practice and Organization of Care (EPOC) category, and clinical outcomes. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation., Data Synthesis: Among the 25 of 243 (10.3%) full-text articles included ( n = 23,215 patients), risk of bias was high in 13 (52%). Most studies were cohort ( n = 22, 88%). A median of 5 (interquartile range [IQR] 4-7) EPOC strategies were used to implement recommendations from two (IQR 2-3) PAD/PADIS domains. Cohort and randomized studies were pooled separately. In the cohort studies, use of EPOC strategies was not associated with a change in mortality (risk ratio [RR] 1.01; 95% CI, 0.9-1.12), or delirium (RR 0.92; 95% CI, 0.82-1.03), but was associated with a reduction in MV duration (weighted mean difference [WMD] -0.84 d; 95% CI, -1.25 to -0.43) and ICU LOS (WMD -0.77 d; 95% CI, -1.51 to 0.04). For randomized studies, EPOC strategy use was associated with reduced mortality and MV duration but not delirium or ICU LOS., Conclusions: Using multiple implementation strategies to adopt PAD/PADIS guideline recommendations may reduce mortality, duration of MV, and ICU LOS. Further prospective, controlled studies are needed to identify the most effective strategies to implement PAD/PADIS recommendations., Competing Interests: Dr. Devlin disclosed he has received research funding from BioExcel, Sedana Medical, and the National Institute of Aging (R13185760, R33HL23452, and R21/R33 AG05797) and that he serves as a consultant to BioExcel, La Jolla Pharmaceuticals, and Ceribell. Dr. Kane-Gill received funding from the Society of Critical Care Medicine. The remaining authors have disclosed that they do not have any potential conflict of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Vitamin C has significant anti-inflammatory effects and is particularly important for critically ill patients. However due to inconsistent research findings in critically ill patients in meta-analysis. Therefore, the primary objective of this meta-analysis is to investigate the effects of isolated intravenous supplementation of vitamin C in adults with critical illness by comprehensively incorporating articles from randomized controlled trials., Methods: Articles included searching through PubMed, Embase, Medline, Cochrane Library, and Web of Science up to April 28, 2023, for articles on vitamin C and the critically ill. We calculated pooled standard relative risk (RR), mean difference (MD), and 95% confidence intervals (CIs). And the protocol for the review has been registered on PROSPERO (CRD42023425193)., Results: There are 2047 critically ill included in 19 articles. Compared with placebo, patients who underwent intravenous vitamin C (IVVC) have reduced duration of vasopressor used (SMD 0.26; CI 0.01-0.51; I2 = 87.0%, P = .044), mechanical ventilation (SMD -0.29; CI -0.55 to -0.03; I2 = 36.8%, P = .031). However, the administration of IVVC had no statistical difference in 28-d mortality (RR 0.95; CI 0.80-1.11; I2 = 12.2%, P = .337), mortality (RR 0.79; CI 0.55-1.12; I2 = 0%, P = .188), fluid intake (SMD -0.02; CI -0.25 to 0.20; I2 = 0%, P = .838), urine output (SMD 0.23; CI -0.03 to 0.49; I2 = 0%, P = .084), ICU days (SMD 0.10; CI -0.03 to 0.22; I2 = 0%, P = .127), hospital stay (SMD 0.10; CI -0.12 to 0.32; I2 = 0%, P = .375), and pneumonia (RR 0.85; CI 0.50-1.44; I2 = 0%, P = .552)., Conclusion: This study comprehensively and systematically evaluated IVVC supplementation in the critically ill through a meta-analysis of RCT. There is no difference except for patients who had reduced duration of vasopressor use and mechanical ventilation by the administration of IVVC. Of course. More scientific and rigorous conclusions can be drawn from multi-center RCT research in the future., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Extracorporeal cardiopulmonary resuscitation (ECPR) serves as a lifesaving intervention for patients experiencing refractory cardiac arrest. With its expanding usage, there is a burgeoning focus on improving patient outcomes through optimal management in the acute phase after cannulation. This review explores systematic post-cardiac arrest management strategies, associated complications, and prognostication in ECPR patients., Data Sources: A PubMed search from inception to 2023 using search terms such as post-cardiac arrest care, ICU management, prognostication, and outcomes in adult ECPR patients was conducted., Study Selection: Selection includes original research, review articles, and guidelines., Data Extraction: Information from relevant publications was reviewed, consolidated, and formulated into a narrative review., Data Synthesis: We found limited data and no established clinical guidelines for post-cardiac arrest care after ECPR. In contrast to non-ECPR patients where systematic post-cardiac arrest care is shown to improve the outcomes, there is no high-quality data on this topic after ECPR. This review outlines a systematic approach, albeit limited, for ECPR care, focusing on airway/breathing and circulation as well as critical aspects of ICU care, including analgesia/sedation, mechanical ventilation, early oxygen/C o2 , and temperature goals, nutrition, fluid, imaging, and neuromonitoring strategy. We summarize common on-extracorporeal membrane oxygenation complications and the complex nature of prognostication and withdrawal of life-sustaining therapy in ECPR. Given conflicting outcomes in ECPR randomized controlled trials focused on pre-cannulation care, a better understanding of hemodynamic, neurologic, and metabolic abnormalities and early management goals may be necessary to improve their outcomes., Conclusions: Effective post-cardiac arrest care during the acute phase of ECPR is paramount in optimizing patient outcomes. However, a dearth of evidence to guide specific management strategies remains, indicating the necessity for future research in this field., Competing Interests: Dr. Bleck received funding from Marinus Pharmaceuticals, SAGE Corporation, iECURE, and Ceribell Corporation. Dr. Whitman received funding from Avania. Dr. Cho is funded by National Heart, Lung, and Blood Institute (1K23HL157610). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objective: Terminal extubation (TE) and terminal weaning (TW) during withdrawal of life-sustaining therapies (WLSTs) have been described and defined in adults. The recent Death One Hour After Terminal Extubation study aimed to validate a model developed to predict whether a child would die within 1 hour after discontinuation of mechanical ventilation for WLST. Although TW has not been described in children, pre-extubation weaning has been known to occur before WLST, though to what extent is unknown. In this preplanned secondary analysis, we aim to describe/define TE and pre-extubation weaning (PW) in children and compare characteristics of patients who had ventilatory support decreased before WLST with those who did not., Design: Secondary analysis of multicenter retrospective cohort study., Setting: Ten PICUs in the United States between 2009 and 2021., Patients: Nine hundred thirteen patients 0-21 years old who died after WLST., Interventions: None., Measurements and Main Results: 71.4% ( n = 652) had TE without decrease in ventilatory support in the 6 hours prior. TE without decrease in ventilatory support in the 6 hours prior = 71.4% ( n = 652) of our sample. Clinically relevant decrease in ventilatory support before WLST = 11% ( n = 100), and 17.6% ( n = 161) had likely incidental decrease in ventilatory support before WLST. Relevant ventilator parameters decreased were F io2 and/or ventilator set rates. There were no significant differences in any of the other evaluated patient characteristics between groups (weight, body mass index, unit type, primary diagnostic category, presence of coma, time to death after WLST, analgosedative requirements, postextubation respiratory support modality)., Conclusions: Decreasing ventilatory support before WLST with extubation in children does occur. This practice was not associated with significant differences in palliative analgosedation doses or time to death after extubation., Competing Interests: Dr. Pringle’s institution received funding from the National Institutes of Health (NIH) (Ul1TR001427); she received support for article research from the NIH. Dr. Winter received support for article research from the LK Whittier Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Changes in arterial partial pressure of carbon dioxide (Pa co2 ) may alter cerebral perfusion in critically ill patients with acute brain injury. Consequently, international guidelines recommend normocapnia in mechanically ventilated patients with acute brain injury. The measurement of end-tidal capnography (Et co2 ) allows its approximation. Our objective was to report the agreement between trends in Et co2 and Pa co2 during mechanical ventilation in patients with acute brain injury., Methods: Retrospective monocenter study was conducted for 2 years. Critically ill patients with acute brain injury who required mechanical ventilation with continuous Et co2 monitoring and with 2 or more arterial gas were included. The agreement was evaluated according to the Bland and Altman analysis for repeated measurements with calculation of bias, and upper and lower limits of agreement. The directional concordance rate of changes between Et co2 and Pa co2 was evaluated with a 4-quadrant plot. A polar plot analysis was performed using the Critchley methods., Results: We analyzed the data of 255 patients with a total of 3923 paired ΔEt co2 and ΔPa co2 (9 values per patient in median). Mean bias by Bland and Altman analysis was -8.1 (95 CI, -7.9 to -8.3) mm Hg. The directional concordance rate between Et co2 and Pa co2 was 55.8%. The mean radial bias by polar plot analysis was -4.4° (95% CI, -5.5 to -3.3) with radial limit of agreement (LOA) of ±62.8° with radial LOA 95% CI of ±1.9°., Conclusions: Our results question the performance of trending ability of Et co2 to track changes in Pa co2 in a population of critically ill patients with acute brain injury. Changes in Et co2 largely failed to follow changes in Pa co2 in both direction (ie, low concordance rate) and magnitude (ie, large radial LOA). These results need to be confirmed in prospective studies to minimize the risk of bias., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2023 International Anesthesia Research Society.)

Objectives: To describe rates and associated risk factors for functional decline 6 months after critical bronchiolitis in a large, multicenter dataset., Design: Nonprespecified secondary analysis of existing 6-month follow-up data of patients in the Randomized Evaluation of Sedation Titration for Respiratory Failure trial ( RESTORE , NCT00814099)., Setting: Patients recruited to RESTORE in any of 31 PICUs in the United States, 2009-2013., Patients: Mechanically ventilated PICU patients under 2 years at admission with a primary diagnosis of bronchiolitis., Interventions: There were no interventions in this secondary analysis; in the RESTORE trial, PICUs were randomized to protocolized sedation versus usual care., Measurements and Main Results: "Functional decline," defined as worsened Pediatric Overall Performance Category and/or Pediatric Cerebral Performance Category (PCPC) scores at 6 months post-PICU discharge as compared with preillness baseline. Quality of life was assessed using Infant Toddler Quality of Life Questionnaire (ITQOL; children < 2 yr old at follow-up) or Pediatric Quality of Life Inventory (PedsQL) at 6 months post-PICU discharge. In a cohort of 232 bronchiolitis patients, 28 (12%) had functional decline 6 months postdischarge, which was associated with unfavorable quality of life in several ITQOL and PedsQL domains. Among 209 patients with normal baseline functional status, 19 (9%) had functional decline. In a multivariable model including all subjects, decline was associated with greater odds of worse baseline PCPC score and longer PICU length of stay (LOS). In patients with normal baseline status, decline was also associated with greater odds of longer PICU LOS., Conclusions: In a random sampling of RESTORE subjects, 12% of bronchiolitis patients had functional decline at 6 months. Given the high volume of mechanically ventilated patients with bronchiolitis, this observation suggests many young children may be at risk of new morbidities after PICU admission, including functional and/or cognitive morbidity and reduced quality of life., Competing Interests: Dr. Watson’s institution received funding from the National Institutes of Health (NIH); he received support for article research from the NIH. Dr. Shein received funding from Ceribell and Hill Ward Henderson. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: To develop and externally validate an intubation prediction model for children admitted to a PICU using objective and routinely available data from the electronic medical records (EMRs)., Design: Retrospective observational cohort study., Setting: Two PICUs within the same healthcare system: an academic, quaternary care center (36 beds) and a community, tertiary care center (56 beds)., Patients: Children younger than 18 years old admitted to a PICU between 2010 and 2022., Interventions: None., Measurements and Main Results: Clinical data was extracted from the EMR. PICU stays with at least one mechanical ventilation event (≥ 24 hr) occurring within a window of 1-7 days after hospital admission were included in the study. Of 13,208 PICU stays in the derivation PICU cohort, 1,175 (8.90%) had an intubation event. In the validation cohort, there were 1,165 of 17,841 stays (6.53%) with an intubation event. We trained a Categorical Boosting (CatBoost) model using vital signs, laboratory tests, demographic data, medications, organ dysfunction scores, and other patient characteristics to predict the need of intubation and mechanical ventilation using a 24-hour window of data within their hospital stay. We compared the CatBoost model to an extreme gradient boost, random forest, and a logistic regression model. The area under the receiving operating characteristic curve for the derivation cohort and the validation cohort was 0.88 (95% CI, 0.88-0.89) and 0.92 (95% CI, 0.91-0.92), respectively., Conclusions: We developed and externally validated an interpretable machine learning prediction model that improves on conventional clinical criteria to predict the need for intubation in children hospitalized in a PICU using information readily available in the EMR. Implementation of our model may help clinicians optimize the timing of endotracheal intubation and better allocate respiratory and nursing staff to care for mechanically ventilated children., Competing Interests: Ms. Chanci, Dr. Grunwell, Mr. Moore, and Dr. Kamaleswaran received support for article research from the National institutes of Health (NIH). Dr. Kamaleswaran’s institution received funding from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: The association between protein intake and the need for mechanical ventilation (MV) is controversial. We aimed to investigate the associations between protein intake and outcomes in ventilated critically ill patients., Design: Analysis of a subset of a large international point prevalence survey of nutritional practice in ICUs., Setting: A total of 785 international ICUs., Patients: A total of 12,930 patients had been in the ICU for at least 96 hours and required MV by the fourth day after ICU admission at the latest., Interventions: None., Measurements and Main Results: We modeled associations between the adjusted hazard rate (aHR) of death in patients requiring MV and successful weaning (competing risks), and three categories of protein intake (low: < 0.8 g/kg/d, standard: 0.8-1.2 g/kg/d, high: > 1.2 g/kg/d). We compared five different hypothetical protein diets (an exclusively low protein intake, a standard protein intake given early (days 1-4) or late (days 5-11) after ICU admission, and an early or late high protein intake). There was no evidence that the level of protein intake was associated with time to weaning. However, compared with an exclusively low protein intake, a standard protein intake was associated with a lower hazard of death in MV: minimum aHR 0.60 (95% CI, 0.45-0.80). With an early high intake, there was a trend to a higher risk of death in patients requiring MV: maximum aHR 1.35 (95% CI, 0.99-1.85) compared with a standard diet., Conclusions: The duration of MV does not appear to depend on protein intake, whereas mortality in patients requiring MV may be improved by a standard protein intake. Adverse effects of a high protein intake cannot be excluded., Competing Interests: Drs. Hartl and Elke received funding from Fresenius Kabi. Dr. Hartl received funding from Biotest. Dr. Kopper disclosed work for hire; he disclosed affiliation with the Munich Center for Machine Learning and LMU/TU Munich. Dr. Elke received funding from Baxter. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Competing Interests: Dr. Kendirli disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Background: Exaggerated lung strain and stress could damage lungs in anesthetized children. The authors hypothesized that the association of capnoperitoneum and lung collapse in anesthetized children increases lung strain-stress. Their primary aim was to describe the impact of capnoperitoneum on lung strain-stress and the effects of an individualized protective ventilation during laparoscopic surgery in children., Methods: The authors performed an observational cohort study in healthy children aged 3 to 7 yr scheduled for laparoscopic surgery in a community hospital. All received standard protective ventilation with 5 cm H2O of positive end-expiratory pressure (PEEP). Children were evaluated before capnoperitoneum, during capnoperitoneum before and after lung recruitment and optimized PEEP (PEEP adjusted to get end-expiratory transpulmonary pressure of 0), and after capnoperitoneum with optimized PEEP. The presence of lung collapse was evaluated by lung ultrasound, positive Air-Test (oxygen saturation measured by pulse oximetry 96% or less breathing 21% O2 for 5 min), and negative end-expiratory transpulmonary pressure. Lung strain was calculated as tidal volume/end-expiratory lung volume measured by capnodynamics, and lung stress as the end-inspiratory transpulmonary pressure., Results: The authors studied 20 children. Before capnoperitoneum, mean lung strain was 0.20 ± 0.07 (95% CI, 0.17 to 0.23), and stress was 5.68 ± 2.83 (95% CI, 4.44 to 6.92) cm H2O. During capnoperitoneum, 18 patients presented lung collapse and strain (0.29 ± 0.13; 95% CI, 0.23 to 0.35; P < 0.001) and stress (5.92 ± 3.18; 95% CI, 4.53 to 7.31 cm H2O; P = 0.374) increased compared to before capnoperitoneum. During capnoperitoneum and optimized PEEP, children presenting lung collapse were recruited and optimized PEEP was 8.3 ± 2.2 (95% CI, 7.3 to 9.3) cm H2O. Strain returned to values before capnoperitoneum (0.20 ± 0.07; 95% CI, 0.17 to 0.22; P = 0.318), but lung stress increased (7.29 ± 2.67; 95% CI, 6.12 to 8.46 cm H2O; P = 0.020). After capnoperitoneum, strain decreased (0.18 ± 0.04; 95% CI, 0.16 to 0.20; P = 0.090), but stress remained higher (7.25 ± 3.01; 95% CI, 5.92 to 8.57 cm H2O; P = 0.024) compared to before capnoperitoneum., Conclusions: Capnoperitoneum increased lung strain in healthy children undergoing laparoscopy. Lung recruitment and optimized PEEP during capnoperitoneum decreased lung strain but slightly increased lung stress. This little rise in pulmonary stress was maintained within safe, lung-protective, and clinically acceptable limits., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Objectives: To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock., Design: Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities., Methods: Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article., Results: A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis?, Conclusions: Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock., Competing Interests: Drs. De Backer, Pontes Azevedo, and Tissieres received funding from Baxter. Dr. De Backer received funding from Edwards Lifesciences, Phillips, and Viatris Pharmazz. Dr. Deutschman received funding from Elsevier, Siemens Healthcare Diagnostics (Tarrytown, NY), Enliven (Jerusalem, Israel), The Society of Critical Care Medicine, the National Institute of General Medical Sciences, and La Jolla Pharmaceuticals; he received support for article research form the National Institutes of Health (NIH); he received Giapreza (angiotensin II infusion) for experimental use from La Jolla Pharmaceuticals (La Jolla, CA); and he received honorarium for serving as Scientific Editor of the journal Critical Care Medicine. Dr. Ostermann received research funding from Baxter, Fresenius Medical, bioMerieux, and La Jolla Pharma. Dr. Talmor received funding from NIH, Clew Medical, Mindray, and STIMIT. Dr. Prescott’s institution received funding from the NIH, U.S. Department of Veterans Affairs, the Agency for Healthcare and Research and Quality, the U.S. Centers for Disease Control and Prevention, and Blue Cross Blue Shield Michigan; she disclosed government work. Dr. Antonelli received funding from General Electrics, Fisher & Paykel, Menarini, and Pfizer. Dr. Pontes Azevedo received funding from Merck Sharp Dohme (MSD) and Nestle. Dr. Loeches received funding from ThermoFisher, Polyphor, MSD, Fresenius Kabi, Gilead, Clinigen, Biotest, Accelerate, and bioMérieux. Dr. Tissieres received funding from Sanofi, bioMerieux, Abionic, Sedana, and ThermoFisher. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Purpose of Review: The response to positive end-expiratory pressure (PEEP) in patients with chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation depends on the underlying pathophysiology. This review focuses on the pathophysiology of COPD, especially intrinsic PEEP (PEEPi) and its consequences, and the benefits of applying external PEEP during assisted ventilation when PEEPi is present., Recent Findings: The presence of expiratory airflow limitation and increased airway resistance promotes the development of dynamic hyperinflation in patients with COPD during acute respiratory failure. Dynamic hyperinflation and the associated development of PEEPi increases work of breathing and contributes to ineffective triggering of the ventilator. In the presence of airflow limitation, application of external PEEP during patient-triggered ventilation has been shown to reduce inspiratory effort, facilitate ventilatory triggering and enhance patient-ventilator interaction. To minimize the risk of hyperinflation, it is advisable to limit the level of external PEEP during assisted ventilation after optimization of ventilator settings to about 70% of the level of PEEPi (measured during passive ventilation)., Summary: In patients with COPD and dynamic hyperinflation receiving assisted mechanical ventilation, the application of low levels of external PEEP can minimize work of breathing, facilitate ventilator triggering and improve patient-ventilator interaction., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Accumulating evidence ascribes the benefit of extracorporeal gas exchange, at least in most severe cases, to the provision of a lung healing environment through the mitigation of ventilator-induced lung injury (VILI) risk. In spite of pretty homogeneous criteria for extracorporeal gas exchange application (according to the degree of hypoxemia/hypercapnia), ventilatory management during extracorporeal membrane oxygenation (ECMO)/carbon dioxide removal (ECCO 2 R) varies across centers. Here we summarize the recent evidence regarding the management of mechanical ventilation during extracorporeal gas exchange for respiratory support., Recent Findings: At present, the most common approach to protect the native lung against VILI following ECMO initiation involves lowering tidal volume and driving pressure, making modest reductions in respiratory rate, while typically maintaining positive end-expiratory pressure levels unchanged.Regarding ECCO 2 R treatment, higher efficiency devices are required in order to reduce significantly respiratory rate and/or tidal volume., Summary: The best compromise between reduction of native lung ventilatory load, extracorporeal gas exchange efficiency, and strategies to preserve lung aeration deserves further investigation., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Serum lactate has been used as a prognostic indicator in intensive care unit patients, and however, the single lactate value may not be enough to reflect changes during illness conditions. Herein, this study aims to explore the association between serum lactate and lactate clearance rate and 30-day mortality in patients undergoing mechanical ventilation (MV). Demographic and clinical data of 2628 adults were extracted from the medical information mart for intensive care-III clinical database in this retrospective cohort study. The lactate clearance rate was calculated using the serum lactate at the beginning of MV (T0), and serum lactate at the12 hours after MV beginning (T1). Univariate and multivariate Cox regression analyses were used to screen covariates, and explore the association between serum lactate and lactate clearance rate and 30-day mortality. We also explored these associations in different T0 serum lactate level subgroups. The evaluation indexes were hazard ratios (HRs) and 95% CIs. In addition, receiver operator characteristic (ROC) curve with area under the curve (AUC) was used to reflect the predictive performance of serum lactate and lactate clearance rate on 30-day mortality. A total of 827 (31.47%) mechanically ventilated patients died within 30 days. After adjusting for covariates, elevated T0 (HR = 1.04, 95%CI: [1.02-1.07]) and T1 (HR = 1.07, 95%CI: [1.04-1.10]) serum lactate was both associated with an increased risk of 30-day mortality, while higher lactate clearance rate was negatively associated with the risk of 30-day mortality (HR = 0.64, 95%CI: [0.50-0.81]). Among patients with T0 lactate ≥2 mmol/L, T1 serum lactate ≥4 mmol/L was associated with an increased risk of 30-day mortality, while lactate clearance rate ≥50 was associated with a decreased risk (all P < .05). Moreover, T1 serum lactate had a potential predictive value on 30-day mortality with an AUC of 0.605. Serum lactate and lactate clearance rate were both associated with 30-day mortality in patients undergoing MV. Our results may provide some references for further studies to explore the roles of serum lactate and lactate clearance rate in prognoses of critical patients., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This 2023 focused update to the neonatal resuscitation guidelines is based on 4 systematic reviews recently completed under the direction of the International Liaison Committee on Resuscitation Neonatal Life Support Task Force. Systematic reviewers and content experts from this task force performed comprehensive reviews of the scientific literature on umbilical cord management in preterm, late preterm, and term newborn infants, and the optimal devices and interfaces used for administering positive-pressure ventilation during resuscitation of newborn infants. These recommendations provide new guidance on the use of intact umbilical cord milking, device selection for administering positive-pressure ventilation, and an additional primary interface for administering positive-pressure ventilation.

Background: Wide interhospital variations exist in cardiovascular intensive care unit (CICU) admission practices and the use of critical care restricted therapies (CCRx), but little is known about the differences in patient acuity, CCRx utilization, and the associated outcomes within tertiary centers., Methods: The Critical Care Cardiology Trials Network is a multicenter registry of tertiary and academic CICUs in the United States and Canada that captured consecutive admissions in 2-month periods between 2017 and 2022. This analysis included 17 843 admissions across 34 sites and compared interhospital tertiles of CCRx (eg, mechanical ventilation, mechanical circulatory support, continuous renal replacement therapy) utilization and its adjusted association with in-hospital survival using logistic regression. The Pratt index was used to quantify patient-related and institutional factors associated with CCRx variability., Results: The median age of the study population was 66 (56-77) years and 37% were female. CCRx was provided to 62.2% (interhospital range of 21.3%-87.1%) of CICU patients. Admissions to CICUs with the highest tertile of CCRx utilization had a greater burden of comorbidities, had more diagnoses of ST-elevation myocardial infarction, cardiac arrest, or cardiogenic shock, and had higher Sequential Organ Failure Assessment scores. The unadjusted in-hospital mortality (median, 12.7%) was 9.6%, 11.1%, and 18.7% in low, intermediate, and high CCRx tertiles, respectively. No clinically meaningful differences in adjusted mortality were observed across tertiles when admissions were stratified by the provision of CCRx. Baseline patient-level variables and institutional differences accounted for 80% and 5.3% of the observed CCRx variability, respectively., Conclusions: In a large registry of tertiary and academic CICUs, there was a >4-fold interhospital variation in the provision of CCRx that was primarily driven by differences in patient acuity compared with institutional differences. No differences were observed in adjusted mortality between low, intermediate, and high CCRx utilization sites., Competing Interests: Disclosures Dr Barnett reports clinical trial enrollment for Acceleron, Merck, Merck Shape & Dohme, and Aerovate Therapeutics. Dr Bohula, Dr Morrow, and J. Guo are members of the TIMI study group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc, Daiichi Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc, Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc, Roche, Siemens Healthcare Diagnostics, Inc, Softcell Medical Limited, The Medicines Company, and Zora Biosciences. Dr Morrow has received consulting fees from Abbott Laboratories, ARCA Biopharma, InCarda, Inflammatix, Merck, Novartis, and Roche Diagnostics. Dr Daniels reports consulting income from Roche Diagnostics and QuidelOrtho serves on clinical end point adjudication committees for Abbottand Applied Therapeutics. Dr Prasad reports advisory board for Abiomed and NIH R01 grant. Dr Teuteberg reports consulting with Abbott, Abiomed advisory board, CareDx advisory board and speaking fees, Cytokinetics speaking fees, Medtronic advisory board, speaking and consulting fees, Paragonix speaking fees, and Takeda advisory board. The other authors report no conflicts.

Background: Diaphragm dysfunction and its effects on outcomes of ventilator weaning have been evaluated in mixed critical care populations using diaphragm thickening fraction (the ratio of the difference between ultrasound diaphragm thickness at end-inspiration and end-expiration to diaphragm thickness at end-expiration) or neuroventilatory efficiency (the ratio of tidal volume and peak electrical activity of the diaphragm). Such data are not available in bilateral-lung transplant recipients. The authors hypothesized that (1) diaphragm dysfunction, as defined by a diaphragm thickening fraction less than 29%, is more likely to occur in difficult weaning; (2) diaphragm thickening fraction and neuroventilatory efficiency predict weaning outcome; and (3) duration of mechanical ventilation before the first spontaneous breathing trial is associated with diaphragm dysfunction., Methods: Adult bilateral-lung transplant patients admitted to the intensive care unit were screened at the time of the first spontaneous breathing trial (pressure-support of 5 cm H2O and 0 positive end-expiratory pressure). At the fifth minute, diaphragm thickening fraction and neuroventilatory efficiency were measured during three respiratory cycles. Weaning was classified as simple, difficult, or prolonged (successful extubation at the first spontaneous breathing trial, within three or after three spontaneous breathing trials, respectively)., Results: Forty-four subjects were enrolled. Diaphragm dysfunction occurred in 14 subjects (32%), all of whom had difficult weaning (78% of the subgroup of 18 patients experiencing difficult weaning). Both diaphragm thickening fraction (24 [20 to 29] vs. 39 [35 to 45]%) and neuroventilatory efficiency (34 [26 to 45] vs. 55 [43 to 62] ml/µV) were lower in difficult weaning (both P < 0.001). The areas under the receiver operator curve predicting difficult weaning were 0.88 (95% CI, 0.73 to 0.99) for diaphragm thickening fraction and 0.85 (95% CI, 0.71 to 0.95) for neuroventilatory efficiency. The duration of ventilation demonstrated a linear inverse correlation with both diaphragm thickening fraction and neuroventilatory efficiency., Conclusions: Diaphragm dysfunction is common after bilateral-lung transplantation and associated with difficult weaning. In such patients, average values for diaphragm thickening fraction and neuroventilatory efficiency were reduced compared to patients with simple weaning. Both parameters showed similar accuracy for predicting success of ventilator weaning, demonstrating an inverse relationship with duration of ventilation., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)