Respiratory microbiome and clinical course of carbapenem-resistant Acinetobacter baumannii pneumonia in critically Ill patients.

Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia has been a serious problem in the intensive care unit (ICU). However, defined characteristics of respiratory microbiome in CRAB pneumonia are lacking nowadays. This study aimed to analyze respiratory microbiome of CRAB pneumonia compared to non-CRAB pneumonia and reveal the clinical significance of respiratory microbiome data in these patients. Patients diagnosed with severe pneumonia with mechanical ventilation were enrolled in the ICU of a tertiary care hospital. Respiratory specimens were collected on days 1, 4, 7, and 14 in each participant via tracheal aspiration. Clinical data and outcomes of each enrolled patient were collected via electronic medical records. Microbiome analysis was conducted with collected respiratory specimens undergone by next-generation sequencing of microbial 16S ribosomal DNA. Six CRAB pneumonia, 4 non-CRAB pneumonia and 5 healthy controls were enrolled. In CRAB pneumonia, CRAB was detected in 3 patients by sputum culture at day 1, while it was negative at day 1 and detected later in the others by follow-up sputum culture. Beta diversity plot analysis showed differences between each group. Shannon index was decreased markedly at day 4 in CRAB pneumonia compared to the others. Among CRAB pneumonia cases, 3 respiratory specimens were culture-negative, but positive by microbiome analysis. Lower respiratory microbiome in CRAB pneumonia had distinct characteristics and early loss of diversity compared to non-CRAB pneumonia, which might be related to poor clinical course. Moreover, CRAB acquisition and colonization would be predicted by preemptive microbiome analysis, which will contribute to effective infection control in the ICU.

The ReInvigorate Study-phrenic nerve-to-diaphragm stimulation for weaning from mechanical ventilation: a protocol for a randomized pivotal clinical trial.

BACKGROUND: In the United States in 2017, there were an estimated 903,745 hospitalizations involving mechanical ventilation (MV). Complications from ventilation can result in longer hospital stays, increased risk of disability, and increased healthcare costs. It has been hypothesized that electrically pacing the diaphragm by phrenic nerve stimulation during mechanical ventilation may minimize or reverse diaphragm dysfunction, resulting in faster weaning. METHODS: The ReInvigorate Trial is a prospective, multicenter, randomized, controlled clinical trial evaluating the safety and efficacy of Stimdia's pdSTIM System for facilitating weaning from MV. The pdSTIM system employs percutaneously placed multipolar electrodes to stimulate the cervical phrenic nerves and activate contraction of the diaphragm bilaterally. Patients who were on mechanical ventilation for at least 96 h and who failed at least one weaning attempt were considered for enrollment in the study. The primary efficacy endpoint was the time to successful liberation from mechanical ventilation (treatment vs. control). Secondary endpoints will include the rapid shallow breathing index and other physiological and system characteristics. Safety will be summarized for both primary and additional analyses. All endpoints will be evaluated at 30 days or at the time of removal of mechanical ventilation, whichever is first. DISCUSSION: This pivotal study is being conducted under an investigational device exception with the U.S. Food and Drug Administration. The technology being studied could provide a first-of-kind therapy for difficult-to-wean patients on mechanical ventilation in an intensive care unit setting. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05998018 , registered August 2023.

Development and validation of a nomogram for predicting mechanical ventilation need among acutely intoxicated patients with impaired consciousness.

BACKGROUND: A considerable portion of acutely intoxicated patients is presented with impaired consciousness. Early identification of those patients who require advanced medical care, such as mechanical ventilation (MV), can improve their prognosis. METHODS: This study included 330 acutely intoxicated patients who were presented with impaired consciousness and admitted to Tanta University Poison Control Center, Egypt, in the period from January 2021 to December 2023. Patients were enrolled in derivation (257 patients) and validation (73 patients) cohorts. Patients' data were analyzed to develop and validate a predictive nomogram to determine the probability of MV need in acutely intoxicated patients. RESULTS: Significant predictors for MV need were mean arterial blood pressure (OR = 0.96, p = .014), PaO2 (OR = 0.96, p = .001), pH (OR = 0.00, p < . 001), and glucose/potassium ratio (OR = 1.59, p = .030). These four parameters were used to formulate a bedside nomogram. Receiver-operating characteristic (ROC) analysis for the proposed nomogram shows that area under the curve (AUC) = 95.7%, accuracy = 93.4%, sensitivity = 88.9%, and specificity = 95.1%. The internal validation for the developed nomogram was assessed using a bootstrapping method and calibration curve. Regarding external validation, AUCs for the developed nomogram probability was 96.5%, and for predicted probability using the developed nomogram was 97.8%. CONCLUSION: The current study provides a validated nomogram that could be used as a reliable tool for the accurate prediction of MV need among acutely intoxicated patients with impaired consciousness. It could assist in the early identification of patients who will require MV, especially in low-income countries with limited resources.

Outcomes of delayed tracheostomy among intubated patients during the coronavirus disease pandemic.

BACKGROUND: Respiratory distress and failure is a complication of the coronavirus disease (COVID-19) and tracheostomy may be necessary in cases of prolonged intubation in order to reduce mechanical ventilation duration. However, according to the Canadian Society of Otolaryngology-Head and Neck Surgery guidelines, which our institution applies, patients should not undergo tracheostomy unless cleared of the virus to reduce its spread among healthcare workers because tracheostomy is an aerosolized procedure. This study aimed to identify the outcomes of prolonged intubation in patients with and without COVID-19 who underwent tracheostomy and to determine the morbidity and mortality rates in both groups. METHODS: This retrospective cohort study included adult patients admitted to the intensive care unit of King Fahad Hospital of the University, Alkhobar, Saudi Arabia, between March 1 and October 31, 2020. This study compared and analyzed the outcomes of delayed tracheostomy in patients with and without COVID-19 in terms of complication, morbidity, and mortality rates. RESULTS: Of the 228 study participants, 111 (48.68%) had COVID-19. The mean age of the study participants was 58.67 years (SD = 17.36, max.=93, min.=20), and the majority were males (n = 149, 65.35%). Regarding tracheostomy in patients with COVID-19, 11 (9.91%) patients underwent tracheostomy; however, four (36.36%) of them had prolonged intubation. The mean intensive care unit admission length of stay for tracheostomy patients was 37.17 days, while it was 12.09 days for patients without tracheostomy (t(226)=-9.32, p < 0.001). Regarding prolonged intubation among patients with COVID-19 (n = 7, 6.31%), the complications were as follows: six people (85.71%) had dysphonia, one (14.29%) had vocal cord granuloma, and two (28.57%) had subglottic tracheal stenosis. The mortality rate among our study participants was 51.32%, and the risk was significantly higher in older people (Odds ratio = 1.04, 95% Confidence Interval [CI] = 1.02-1.06) and in delayed tracheostomy cases (OR = 2.95, 95% CI = 1.31-6.63). However, COVID-19 status was not significantly related to the risk of mortality. CONCLUSIONS: Delaying tracheostomy increases the risk of mortality. Therefore, we recommend weighing the risks and benefits for each patient to benefit both healthcare workers and patients with COVID-19.

Use of pressure muscle index to guide pressure support ventilation setting: a study protocol and statistical plan for a prospective randomised controlled proof-of-concept trial.

INTRODUCTION: Although pressure support ventilation is one of the most commonly used assisted ventilation modes in intensive care units, there is still a lack of precise strategies for setting pressure support. By performing an end-inspiratory airway occlusion, the difference between the peak and plateau airway pressure, which is defined as pressure muscle index (PMI), can be easily measured on the ventilator screen. Previous studies have shown that PMI is accurate in detecting high and low inspiratory effort. No study has been conducted to investigate the use of PMI as an indicator for setting inspiratory pressure support. METHOD AND ANALYSIS: This is a study protocol for a prospective, single-centre, randomised controlled, pilot trial. Sixty participants undergoing pressure support ventilation will be randomly assigned in a 1:1 ratio to the control group or intervention group, with pressure support adjusted according to standard care or guided by the PMI strategy for 48 hours, respectively. The feasibility of the PMI-guided strategy will be evaluated. The primary endpoint is the proportion of inspiratory effort measurements within a well-accepted 'normal' range, which is predefined as oesophageal pressure-time product per minute between 50 and 200 cmH2O⋅s/min, for each patient during 48 hours of pressure support adjustment. ETHICS AND DISSEMINATION: The study protocol has been approved by Beijing Tiantan Hospital (KY2023-005-02). The data generated in the present study will be available from the corresponding author on reasonable request. The results of the trial will be submitted to international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05963737; ClinicalTrials.org.

Bleeding is associated with severely impaired outcomes in surgery for acute type a aortic dissection.

Background. Surgery for acute type A aortic dissection confers a risk for significant bleeding. We analyzed the impact of massive bleeding on complications after surgery for acute type A aortic dissection. Methods. Patients undergoing surgery for acute type A aortic dissection from the retrospective multicenter Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) database 2005-2014 were eligible. Massive bleeding was defined according to the Universal Definition of Perioperative Bleeding. The primary outcome measure was early mortality and secondary outcome measures were perioperative stroke, mechanical ventilation more than 48 h, new-onset dialysis, and intensive care unit stay. Propensity score matching was performed to adjust for differences in covariates. Results. Nine hundred ninety-seven patients were included, of whom 403 (40.4%) had massive bleeding. In the propensity score-matched cohort (344 pairs), patients with massive bleeding had higher 30-day mortality (17.2 versus 7.6%, p < .001), mechanical ventilation more than 48 h (52.8 versus 22.6%, p < .001), perioperative stroke (24.3 versus 14.8%, p = .002), new-onset dialysis (22.5 versus 4.9%, p < .001), and longer intensive care unit stay (6 versus 3 days, p < .001), compared with patients without massive bleeding. Risk factors for massive bleeding were previous cardiac surgery, preoperative clopidogrel or ticagrelor therapy, DeBakey type I dissection, and localized or generalized malperfusion. Conclusions. Massive bleeding in surgery for acute type A aortic dissection is associated with a markedly increased risk for severe complications as well as early death. Further improvement of surgical technique and pharmacological optimization of coagulation is paramount to possibly improve outcomes in acute type A aortic dissection repair.

Complications of new-onset atrial fibrillation in critically ill COVID-19 patients admitted to the intensive care unit (ICU): a meta-analysis.

BACKGROUND: COVID-19 infections can result in severe acute respiratory distress syndrome (ARDS) requiring admission to the intensive care unit (ICU). Cardiovascular manifestation or exacerbation of cardiovascular diseases could be another complication. Cardiac arrhythmias including New-Onset Atrial Fibrillation (NOAF), have been observed in hospitalized patients with COVID-19 infections. In this analysis, we aimed to systematically compare the complications associated with NOAF in critically ill COVID-19 patients admitted to the ICU. METHODS: MEDLINE, EMBASE, Web of Science, the Cochrane database, http://www. CLINICALTRIALS: gov , Google Scholar and Mendeley were searched for relevant publications based on COVID-19 patients with NOAF admitted to the ICU. Complications including in-hospital mortality, ICU mortality, patients requiring mechanical ventilation, acute myocardial infarction, acute kidney injury, renal replacement therapy and pulmonary embolism were assessed. This is a meta-analysis and the analytical tool which was used was the RevMan software version 5.4. Risk ratios (RR) and 95% confidence intervals (CIs) were used to represent the data post analysis. RESULTS: In critically ill COVID-19 patients with NOAF admitted to the ICU, the risks of ICU mortality (RR: 1.39, 95% CI: 1.07 - 1.80; P = 0.01), in-hospital mortality (RR: 1.56, 95% CI: 1.20 - 2.04; P = 0.001), patients requiring mechanical ventilation (RR: 1.32, 95% CI: 1.04 - 1.66; P = 0.02) were significantly higher when compared to the control group without AF. Acute myocardial infarction (RR: 1.54, 95% CI: 1.31 - 1.81; P = 0.00001), the risk for acute kidney injury (RR: 1.31, 95% CI: 1.11 - 1.55; P = 0.002) and patients requiring renal replacement therapy (RR: 1.83, 95% CI: 1.60 - 2.09; P = 0.00001) were also significantly higher in patients with NOAF. CONCLUSIONS: Critically ill COVID-19 patients with NOAF admitted to the ICU were at significantly higher risks of developing complications and death compared to similar patients without AF.

Adherence to low tidal volume in the transition to spontaneous ventilation in patients with acute respiratory failure in intensive care units in Latin America (SPIRAL): a study protocol.

OBJECTIVE: Patients with acute respiratory failure often require mechanical ventilation to reduce the work of breathing and improve gas exchange; however, this may exacerbate lung injury. Protective ventilation strategies, characterized by low tidal volumes (≤ 8mL/kg of predicted body weight) and limited plateau pressure below 30cmH2O, have shown improved outcomes in patients with acute respiratory distress syndrome. However, in the transition to spontaneous ventilation, it can be challenging to maintain tidal volume within protective levels, and it is unclear whether low tidal volumes during spontaneous ventilation impact patient outcomes. We developed a study protocol to estimate the prevalence of low tidal volume ventilation in the first 24 hours of spontaneous ventilation in patients with hypoxemic acute respiratory failure and its association with ventilator-free days and survival. METHODS: We designed a multicenter, multinational, cohort study with a 28-day follow-up that will include patients with acute respiratory failure, defined as a partial oxygen pressure/fraction of inspired oxygen ratio < 300mmHg, in transition to spontaneous ventilation in intensive care units in Latin America. RESULTS: We plan to include 422 patients in ten countries. The primary outcomes are the prevalence of low tidal volume in the first 24 hours of spontaneous ventilation and ventilator-free days on day 28. The secondary outcomes are intensive care unit and hospital mortality, incidence of asynchrony and return to controlled ventilation and sedation. CONCLUSION: In this study, we will assess the prevalence of low tidal volume during spontaneous ventilation and its association with clinical outcomes, which can inform clinical practice and future clinical trials.

Association between glucocorticoid administration and outcomes in patients with ARDS based on the MIMIC-III database.

This study aimed to investigate the association between glucocorticoid administration and outcomes in critically ill patients with ARDS using the Medical Information Mart for Intensive Care (MIMIC)-III database. Data were collected from the MIMIC-III database, which consists of critically ill participants between 2001 and 2012 in the USA. A total of 1831 adult critically ill patients with ARDS were enrolled from the MIMIC-III database. The 60-day and in-hospital mortality, were the primary endpoints. Secondary outcomes included length of stay (LOS) in the hospital and intensive care unit (ICU), 28-day ventilator-free days, ICU mortality, and 28-day mortality. A total of 1831 patients were included in the data analysis. After propensity score (PS) matching, 464 patients diagnosed with ARDS were matched between the glucocorticoid treatment and control groups. Glucocorticoids were associated with increased in-hospital mortality [hazard ratio (HR) 1.32; 95% CI 1.01-1.71; P = .039], longer ICU stay [HR 2.25; 95% CI 0.84-3.65; P = .002], and shorter ventilation-free days at 28 days in all ARDS patients [HR -2.70; 95% CI -4.28--1.13; P = .001]. The 60-day mortality was higher in the glucocorticoid group (44.83% vs 35.34%; P = .154; HR 1.24; 95% CI 0.93-1.66). Excluding the impact of the glucocorticoid initiation time, from day 15 to day 60, mortality was significantly higher in the glucocorticoid group compared to the non-glucocorticoid group (27.16% vs 12.70%; P < .001; HR 1.75; 95% CI 1.32-2.32). Glucocorticoid administration was associated with worse 60-day and in-hospital survival, longer ICU stay, and shorter ventilator-free days on day 28 in patients with ARDS. Our findings suggest careful consideration of glucocorticoids for ARDS.

Intracranial compliance in patients with COVID-19: a multicenter observational study.

BACKGROUND: Patients with severe coronavirus disease-19 (COVID-19) may require the use of invasive mechanical ventilation (MV) for prolonged periods. Aggressive MV parameters have been associated with changes in intracranial pressure (ICP) in patients with acute intracranial disorders. Significant ICP elevation could compromise intracranial compliance (ICC) and cerebrovascular hemodynamics (CVH). However, the effects of these parameters in individuals without neurological disorders have not yet been evaluated. OBJECTIVE: To evaluate ICC in patients on MV with COVID-19 infection compared to other diagnoses, to better characterize the effects of MV and COVID-19 upon ICC. We also compared between the ICC in patients with COVID-19 who did not require MV and healthy volunteers, to assess the isolated effect of COVID-19 upon ICC. METHODS: This was an exploratory, observational study with a convenience sample. The ICC was evaluated with a noninvasive ICP monitoring device. The P2/P1 ratio was calculated by dividing the amplitude of these two points, being defined as "abnormal" when P2 > P1. The statistical analysis was performed using a mixed linear model with random effects to compare the P2/P1 ratio in all four groups on the first monitoring day. RESULTS: A convenience sample of 78 subjects (15 MV-COVID-19, 15 MV non-COVID-19, 24 non-MV-COVID-19, and 24 healthy participants) was prospectively enrolled. There was no difference in P2/P1 ratios between MV patients with and without COVID-19, nor between non-MV patients with COVID-19 and healthy volunteers. However, the P2/P1 ratio was higher in COVID-19 patients with MV use than in those without it. CONCLUSION: This exploratory analysis suggests that COVID-19 does not impair ICC.

ANTECEDENTES: Pacientes com doença grave por coronavírus-19 (COVID-19) podem necessitar do uso de ventilação mecânica (VM) invasiva por um período prolongado. Parâmetros agressivos de VM têm sido associados a alterações na pressão intracraniana (PIC) em pacientes com doenças intracranianas agudas. Elevações significativas da PIC podem comprometer a complacência intracraniana (CIC) e a hemodinâmica cerebrovascular (HVC). No entanto, os efeitos desses parâmetros em indivíduos sem doenças neurológicas ainda não foram sistematicamente avaliados. OBJETIVO: Avaliar a CIC em pacientes em VM com COVID-19 comparados com outros diagnósticos, para melhor caracterizar os efeitos da VM e COVID-19 sobre a CIC. Também foi feita a comparação entre a CIC em pacientes com COVID-19 sem VM e voluntários saudáveis, para avaliar o efeito isolado da COVID-19 sobre a ICC. MéTODOS: Trata-se de um estudo exploratório, observacional com amostra por conveniência. A CIC foi avaliada com um dispositivo não invasivo de monitoramento da PIC. A relação P2/P1 foi calculada dividindo-se a amplitude desses dois pontos, sendo definida como "anormal" quando P2 > P1. A análise estatística foi realizada usando um modelo linear misto com efeitos aleatórios para comparar a relação P2/P1 nos quatro grupos no primeiro dia de monitoramento. RESULTADOS: Uma amostra de conveniência com 78 voluntários (15 COVID-19 em VM, 15 sem COVID-19 em VM, 24 com COVID em respiração espontânea e 24 saudáveis) foram prospectivamente incluídos. Não houve diferença nas razões P2/P1 entre pacientes em VM com e sem COVID-19, nem entre pacientes sem VM com COVID-19 ou saudáveis. No entanto, a relação P2/P1 foi maior em pacientes com COVID-19 com uso de VM do que naqueles sem. CONCLUSãO: Os dados dessa análise exploratória sugerem que a COVID-19 não prejudica a CIC.

Patients' experiences of mechanical ventilation in intensive care units in low- and lower-middle-income countries: protocol of a systematic review.

BACKGROUND: Mechanical ventilation (MV) in intensive care units (ICUs) is a stressful experience for patients. However, these experiences have not been systematically explored in low- and lower-middle-income countries (LLMICs). This systematic review (SR) aims to explore the patients' experiences of MV in ICUs in LLMICs and the factors influencing their experiences. METHODS: The PICO framework will be used to operationalize the review question into key concepts: population (mechanically ventilated adult patients in ICUs), phenomenon of interest (experiences) and context (LLMICs). PubMed, Embase, PsycINFO, CINAHL, Cochrane Library, Scopus and Web of Science will be systematically searched since database inception. Citation, reference list and PubMed-related article searching of included studies will be done to ensure literature saturation. Empirical peer-reviewed literature exploring adult patients' (aged ≥ 18 years) experiences of MV in ICUs in LLMIC will be included. All study designs (quantitative, qualitative and mixed methods) will be included. Two independent reviewers will perform screening, data extraction and critical appraisal. The mixed-methods appraisal tool (MMAT) and Popay's narrative synthesis will be used for critical appraisal and data synthesis, respectively. DISCUSSION: This SR aims to bridge a gap in knowledge as previous evidence synthesis has described this phenomenon in developed countries. The review design, with the inclusion of quantitative, qualitative and mixed-methods studies, intends to provide a rich and in-depth exploration of the issue. The findings will be presented as themes, subthemes and their explanatory narratives. The gaps in available literature will be identified, and implications of SR findings on policy, practice and future research will be presented. The strength of this SR lies in its systematic, comprehensive, transparent, robust and explicit methodology of identifying, collating, assessing and synthesizing available evidence. By prior registration and reporting of this SR protocol, we aim to ensure transparency and accountability and minimize bias. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42024507187.

Device associated complications in the intensive care unit.

Invasive devices are routinely used in the care of critically ill patients. Although they are often essential components of patient care, devices such as intravascular catheters, endotracheal tubes, and ventilators are a common source of complications in the intensive care unit. Critical care practitioners who use these devices need to use strategies for risk reduction and understand approaches to management when adverse events occur. This review discusses the identification, prevention, and management of complications of vascular, airway, and mechanical support devices commonly used in the intensive care unit.

Proportion of confluent B-Lines predicts respiratory support in term infants shortly after birth.

OBJECTIVE: To develop and evaluate the predictive value of a simplified lung ultrasound (LUS) method for forecasting respiratory support in term infants. METHODS: This observational, prospective, diagnostic accuracy study was conducted in a tertiary academic hospital between June and December 2023. A total of 361 neonates underwent LUS examination within 1 h of birth. The proportion of each LUS sign was utilized to predict their respiratory outcomes and compared with the LUS score model. After identifying the best predictive LUS sign, simplified models were created based on different scan regions. The optimal simplified model was selected by comparing its accuracy with both the full model and the LUS score model. RESULTS: After three days of follow-up, 91 infants required respiratory support, while 270 remained healthy. The proportion of confluent B-lines demonstrated high predictive accuracy for respiratory support, with an area under the curve (AUC) of 89.1% (95% confidence interval [CI]: 84.5-93.7%). The optimal simplified model involved scanning the R/L 1-4 region, yielding an AUC of 87.5% (95% CI: 82.6-92.3%). Both the full model and the optimal simplified model exhibited higher predictive accuracy compared to the LUS score model. The optimal cut-off value for the simplified model was determined to be 15.9%, with a sensitivity of 76.9% and specificity of 91.9%. CONCLUSIONS: The proportion of confluent B-lines in LUS can effectively predict the need for respiratory support in term infants shortly after birth and offers greater reliability than the LUS score model.

Ulinastatin shortens the length of ICU stay in critical patients with organ failure: A 7-year real-world study.

BACKGROUND: Ulinastatin has been applied in a series of diseases associated with inflammation but its clinical effects remain somewhat elusive. OBJECTIVE: We aimed to investigate the potential effects of ulinastatin on organ failure patients admitted to the intensive care unit (ICU). METHODS: This is a single-center retrospective study on organ failure patients from 2013 to 2019. Patients were divided into two groups according to using ulinastatin or not during hospitalization. Propensity score matching was applied to reduce bias. The outcomes of interest were 28-day all-cause mortality, length of ICU stay, and mechanical ventilation duration. RESULTS: Of the 841 patients who fulfilled the entry criteria, 247 received ulinastatin. A propensity-matched cohort of 608 patients was created. No significant differences in 28-day mortality between the two groups. Sequential organ failure assessment (SOFA) was identified as the independent risk factor associated with mortality. In the subgroup with SOFA ≤ 10, patients received ulinastatin experienced significantly shorter time in ICU (10.0 d [interquartile range, IQR: 7.0∼20.0] vs 15.0 d [IQR: 7.0∼25.0]; p = .004) and on mechanical ventilation (222 h [IQR:114∼349] vs 251 h [IQR: 123∼499]; P = .01), but the 28-day mortality revealed no obvious difference (10.5% vs 9.4%; p = .74). CONCLUSION: Ulinastatin was beneficial in treating patients in ICU with organ failure, mainly by reducing the length of ICU stay and duration of mechanical ventilation.

Mechanical ventilation guided by driving pressure optimizes local pulmonary biomechanics in an ovine model.

Mechanical ventilation exposes the lung to injurious stresses and strains that can negatively affect clinical outcomes in acute respiratory distress syndrome or cause pulmonary complications after general anesthesia. Excess global lung strain, estimated as increased respiratory system driving pressure, is associated with mortality related to mechanical ventilation. The role of small-dimension biomechanical factors underlying this association and their spatial heterogeneity within the lung are currently unknown. Using four-dimensional computed tomography with a voxel resolution of 2.4 cubic millimeters and a multiresolution convolutional neural network for whole-lung image segmentation, we dynamically measured voxel-wise lung inflation and tidal parenchymal strains. Healthy or injured ovine lungs were evaluated as the mechanical ventilation positive end-expiratory pressure (PEEP) was titrated from 20 to 2 centimeters of water. The PEEP of minimal driving pressure (PEEPDP) optimized local lung biomechanics. We observed a greater rate of change in nonaerated lung mass with respect to PEEP below PEEPDP compared with PEEP values above this threshold. PEEPDP similarly characterized a breaking point in the relationships between PEEP and SD of local tidal parenchymal strain, the 95th percentile of local strains, and the magnitude of tidal overdistension. These findings advance the understanding of lung collapse, tidal overdistension, and strain heterogeneity as local triggers of ventilator-induced lung injury in large-animal lungs similar to those of humans and could inform the clinical management of mechanical ventilation to improve local lung biomechanics.

Daily Sedation Interruption vs Continuous Sedation in Pediatric Patients Receiving Mechanical Ventilation: A Systematic Review and Meta-analysis.

Importance: The effectiveness of daily sedation interruption (DSI, defined as temporary interruption of sedation) has yet to be demonstrated in critically ill pediatric patients. Objective: To compare the clinical outcomes of DSI vs continuous intravenous (IV) sedation in patients receiving invasive mechanical ventilation (MV) support in the pediatric intensive care unit (PICU). Data Sources: A systematic search for studies was conducted using predefined keywords and Medical Subject Headings in 5 major databases (PubMed, Embase, Web of Science, CINAHL [Cumulated Index to Nursing and Allied Health Literature], and Cochrane Central Register of Controlled Trials) from database inception to October 31, 2023. Study Selection: Retrospective and prospective observational studies, randomized clinical trials (RCTs), and systematic reviews were assessed for inclusion. Studies were eligible if they compared DSI to continuous IV sedation in patients aged 18 years or younger requiring MV in the PICU. Data Extraction and Synthesis: Study characteristics, including the types of sedation, sedation protocols, and clinical outcomes, were extracted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed. A random-effects model was used to pool results from articles for the meta-analysis. Main Outcomes and Measures: The primary outcomes of interest were duration of MV and length of PICU stay. Secondary outcomes included total sedative dose requirement, adverse events (eg, complications associated with MV, withdrawal, and delirium), and mortality. Results: A total of 6 RCTs with 2810 pediatric patients (1569 males [55.8%]; mean age, 26.5 [95% CI, 15.0-37.9] months) were included in the final analysis; patients had a mean PRISM (Pediatric Risk of Mortality) score of 13.68 (95% CI, 10.75-16.61). Compared with continuous IV sedation, DSI was associated with a reduction in length of PICU stay (5 studies, n = 2770; mean difference [MD], -1.45 [95% CI, -2.75 to -0.15] days; P = .03]. There was no difference in MV duration (5 studies, n = 2750; MD, -0.93 [95% CI, -1.89 to 0.04] days; P = .06), total doses of midazolam (3 studies, n = 191; MD, -1.66 [95% CI, -3.95 to 0.63] mg/kg) and morphine used (2 studies, n = 189; MD, -2.63 [95% CI, -7.01 to 1.75] mg/kg), or adverse events (risk ratio [RR], 1.03 [95% CI, 0.74-1.42]; P = .88). There was no difference in mortality between patients exposed vs not exposed to DSI (RR, 0.89 [95% CI, 0.55-1.46]; P = .65). Conclusions and Relevance: This systematic review and meta-analysis found that use of DSI in pediatric patients was associated with reduced length of PICU stay with no increase in adverse events. Further research is needed to ascertain whether this strategy is associated with improved neurodevelopmental outcomes in PICU survivors.

Longer ICU stay and invasive mechanical ventilation accelerate telomere shortening in COVID-19 patients 1 year after recovery.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes virus-induced-senescence. There is an association between shorter telomere length (TL) in coronavirus disease 2019 (COVID-19) patients and hospitalization, severity, or even death. However, it remains unknown whether virus-induced-senescence is reversible. We aim to evaluate the dynamics of TL in COVID-19 patients 1 year after recovery from intensive care units (ICU). Longitudinal study enrolling 49 patients admitted to ICU due to COVID-19 (August 2020 to April 2021). Relative telomere length (RTL) quantification was carried out in whole blood by monochromatic multiplex real-time quantitative PCR (MMqPCR) assay at hospitalization (baseline) and 1 year after discharge (1-year visit). The association between RTL and ICU length of stay (LOS), invasive mechanical ventilation (IMV), prone position, and pulmonary fibrosis development at 1-year visit was evaluated. The median age was 60 years, 71.4% were males, median ICU-LOS was 12 days, 73.5% required IMV, and 38.8% required a prone position. Patients with longer ICU-LOS or who required IMV showed greater RTL shortening during follow-up. Patients who required pronation had a greater RTL shortening during follow-up. IMV patients who developed pulmonary fibrosis showed greater RTL reduction and shorter RTL at the 1-year visit. Patients with longer ICU-LOS and those who required IMV had a shorter RTL in peripheral blood, as observed 1 year after hospital discharge. Additionally, patients who required IMV and developed pulmonary fibrosis had greater telomere shortening, showing shorter telomeres at the 1-year visit. These patients may be more prone to develop cellular senescence and lung-related complications; therefore, closer monitoring may be needed.

Effect of Early Versus Delayed Tracheostomy Strategy on Functional Outcome of Patients With Severe Traumatic Brain Injury: A Target Trial Emulation.

OBJECTIVES: Optimal timing of tracheostomy in severe traumatic brain injury (TBI) is unknown due to lack of clinical trials. We emulated a target trial to estimate the effect of early vs. delayed tracheostomy strategy on functional outcome of patients with severe TBI. DESIGN: Target trial emulation using 1:1 balanced risk-set matching. SETTING: North American hospitals participating in the TBI Hypertonic Saline randomized controlled trial of the Resuscitation Outcomes Consortium. PATIENTS: The prematching population consisted of patients with TBI and admission Glasgow Coma Scale less than or equal to 8, who were alive and on mechanical ventilation on the fourth day following trial enrollment, and stayed in the ICU for at least 5 days. Patients with absolute indication for tracheostomy and patients who died during the first 28 days with a decision to withdraw care were excluded. INTERVENTIONS: We matched patients who received tracheostomy at a certain timepoint (early group) with patients who had not received tracheostomy at the same timepoint but were at-risk of tracheostomy in the future (delayed group). The primary outcome was a poor 6-month functional outcome, defined as Glasgow Outcome Scale-Extended less than or equal to 4. MEASUREMENTS AND MAIN RESULTS: Out of 1282 patients available for analysis, 275 comprised the prematching population, with 75 pairs being created postmatching. Median time of tracheostomy differed significantly in the early vs. the delayed group (7.0 d [6.0-10.0 d] vs. 12.0 d [9.8-18.3 d]; p < 0.001). Only 40% of patients in the delayed group received tracheostomy. There was no statistically significant difference between groups regarding poor 6-month functional outcome (early: 68.0% vs. delayed: 72.0%; p = 0.593). CONCLUSIONS: In a target trial emulation, early as opposed to delayed tracheostomy strategy was not associated with differences in 6-month functional outcome following severe TBI. Considering the limitations of target trial emulations, delaying tracheostomy through a "watchful waiting" approach may be appropriate.

Associations of early changes in lung ultrasound aeration scores and mortality in invasively ventilated patients: a post hoc analysis.

BACKGROUND: Lung ultrasound (LUS) in an emerging technique used in the intensive care unit (ICU). The derivative LUS aeration score has been shown to have associations with mortality in invasively ventilated patients. This study assessed the predictive value of baseline and early changes in LUS aeration scores in critically ill invasively ventilated patients with and without ARDS (Acute Respiratory Distress Syndrome) on 30- and 90-day mortality. METHODS: This is a post hoc analysis of a multicenter prospective observational cohort study, which included patients admitted to the ICU with an expected duration of ventilation for at least 24 h. We restricted participation to patients who underwent a 12-region LUS exam at baseline and had the primary endpoint (30-day mortality) available. Logistic regression was used to analyze the primary and secondary endpoints. The analysis was performed for the complete patient cohort and for predefined subgroups (ARDS and no ARDS). RESULTS: A total of 442 patients were included, of whom 245 had a second LUS exam. The baseline LUS aeration score was not associated with mortality (1.02 (95% CI: 0.99 - 1.06), p = 0.143). This finding was not different in patients with and in patients without ARDS. Early deterioration of the LUS score was associated with mortality (2.09 (95% CI: 1.01 - 4.3), p = 0.046) in patients without ARDS, but not in patients with ARDS or in the complete patient cohort. CONCLUSION: In this cohort of critically ill invasively ventilated patients, the baseline LUS aeration score was not associated with 30- and 90-day mortality. An early change in the LUS aeration score was associated with mortality, but only in patients without ARDS. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT04482621.