IGF-1 Regulates Skeletal Muscle Degradation and Remolding in Ventilator-Induced Diaphragmatic Dysfunction by Mediating FOXO1 Expression.

BACKGROUND: Mechanical ventilation (MV) sustains life in critically ill patients by providing adequate alveolar ventilation. However, prolonged MV could induce inspiratory muscle atrophy known as ventilator-induced diaphragmatic dysfunction (VIDD). Insulin-like growth factor (IGF)-1 has been proven to play crucial roles in regulating skeletal muscle size and function. Meanwhile, the forkhead box protein O1 (FOXO1) has been linked to muscle atrophy. This study aimed to explore the effect of IGF-1 on muscle degradation and remodeling in VIDD and delved into the association of the underlying mechanism involving FOXO1. METHODS: VIDD models were established by treating rats with MV. Adeno-associated virus (AAV) was used for transfection to construct IGF-1 and/or FOXO1 overexpressed rats. There were four groups in this study: normal rats (NC), normal rats with MV treatment (MV), IGF-1-overexpressed rats with MV treatment (MV+IGF-1), and rats overexpressing both IGF-1 and FOXO1 with MV treatment (MV+IGF-1+FOXO1). Protein levels were measured by western blot or enzyme-linked immunosorbent assay (ELISA), and mRNA levels were detected by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). IGF-1 and FOXO1 expression were validated by detecting mRNA and protein levels. Diaphragmatic muscle contractility and morphometry were tested using stimulating electrodes in conjunction with hematoxylin and eosin (H&E) staining. Interleukin (IL)-6 and carbonylated protein were used for evaluating muscle atrophy and oxidation, respectively. Protein degradation was determined by troponin-I level and tyrosine release. Apoptosis was assessed using the terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate (UTP) nick-end labeling (TUNEL) assay, alongside markers like Bax, B-cell lymphoma 2 (BCL-2), and Cleaved Caspase-3. Atrogin-1, muscle RING finger 1 (MURF1), neuronally expressed developmentally downregulated 4 (NEDD4), muscle ubiquitin ligase of SCF complex in atrophy-1 (MUSA1), and ubiquitinated protein was used to determine proteolysis. Additionally, protein synthesis was measured by assessing the rates of mixed muscle protein (MMP) and myosin heavy chain (MHC). RESULTS: MV treatment caused IGF-1 downregulation (p < 0.01) and FOXO1 upregulation (p < 0.01). The IGF-1 upregulation downregulated FOXO1 in the MV+IGF-1 group (p < 0.001) while IGF-1 and FOXO1 were both upregulated in the MV+IGF-1+FOXO1 group (p < 0.001). The treatment of MV decreased muscle contractility and cross-sectional areas of diaphragm muscle fibers (p < 0.01). Additionally, IL-6, troponin-1, tyrosine release, carbonylated protein, TUNEL positive nuclei, Bax, Cleaved Caspase-3, Atrogin-1, MURF1, neuronally expressed developmentally downregulated 4 (NEDD4), MUSA1, and ubiquitinated protein levels increased significantly in MV group (p < 0.001) while levels of BCL-2, fractional synthetic rate of MMP and MHC, and type I and type II MHC protein mRNA expression decreased in MV group (p < 0.001). All of these alterations were reversed in the MV+IGF-1 group (p < 0.01), while the IGF-1-induced reversion was disrupted in the MV+IGF-1+FOXO1 group (p < 0.01). CONCLUSIONS: IGF-1 may protect diaphragmatic muscles from VIDD-induced structural damage and function loss by downregulating FOXO1. This action suppresses muscle breakdown and facilitates muscle remodeling in diaphragmatic muscles affected by VIDD.

A Survey of PICU Clinician Practices and Perceptions regarding Respiratory Cultures in the Evaluation of Ventilator-Associated Infections in the BrighT STAR Collaborative.

OBJECTIVES: To characterize respiratory culture practices for mechanically ventilated patients, and to identify drivers of culture use and potential barriers to changing practices across PICUs. DESIGN: Cross-sectional survey conducted May 2021-January 2022. SETTING: Sixteen academic pediatric hospitals across the United States participating in the BrighT STAR Collaborative. SUBJECTS: Pediatric critical care medicine physicians, advanced practice providers, respiratory therapists, and nurses. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We summarized the proportion of positive responses for each question within a hospital and calculated the median proportion and IQR across hospitals. We correlated responses with culture rates and compared responses by role. Sixteen invited institutions participated (100%). Five hundred sixty-eight of 1,301 (44%) e-mailed individuals completed the survey (median hospital response rate 60%). Saline lavage was common, but no PICUs had a standardized approach. There was the highest variability in perceived likelihood (median, IQR) to obtain cultures for isolated fever (49%, 38-61%), isolated laboratory changes (49%, 38-57%), fever and laboratory changes without respiratory symptoms (68%, 54-79%), isolated change in secretion characteristics (67%, 54-78%), and isolated increased secretions (55%, 40-65%). Respiratory cultures were likely to be obtained as a "pan culture" (75%, 70-86%). There was a significant correlation between higher culture rates and likelihood to obtain cultures for isolated fever, persistent fever, isolated hypotension, fever, and laboratory changes without respiratory symptoms, and "pan cultures." Respondents across hospitals would find clinical decision support (CDS) helpful (79%) and thought that CDS would help align ICU and/or consulting teams (82%). Anticipated barriers to change included reluctance to change (70%), opinion of consultants (64%), and concern for missing a diagnosis of ventilator-associated infections (62%). CONCLUSIONS: Respiratory culture collection and ordering practices were inconsistent, revealing opportunities for diagnostic stewardship. CDS would be generally well received; however, anticipated conceptual and psychologic barriers to change must be considered.

[A new type of artificial airway sealer used between artificial airway and ventilator pipeline].

The need for mechanical ventilation due to severe hypoxemia and acute respiratory distress syndrome has increased dramatically in the global pandemic of severe respiratory infectious diseases. In clinical scenarios, it is sometimes necessary to briefly disconnect the ventilator pipeline from the artificial airway. Still, this operation can lead to a sharp drop in airway pressure, which is contrary to the protective lung ventilation strategy and increases the risk of environmental exposure to bioaerosol, posing a serious threat to patients and medical workers. At present, there is yet to be a practical solution. A new artificial airway device was designed by the medical staff from the department of critical care medicine of Beijing Tiantan Hospital, Capital Medical University, based on many years of research experience in respiratory support therapy, and recently obtained the National Utility Model Patent of China (ZL 2019 2 0379605.4). The device comprises two connecting pipes, the sealing device body, and the globe valve represented by the iridescent optical ring. It has a simple structure, convenient operation, and low production cost. The device is installed between the artificial airway and the ventilator pipeline and realizes the instantaneous sealing of the artificial airway by adjusting the shut-off valve. Using this device to treat mechanically ventilated patients can minimize the ventilator-induced lung injury caused by the repeated disconnection of pipelines, avoid iatrogenic transmission of bioaerosols, and realize dual protection for patients and medical workers. It has extensive clinical application prospects and high health and economic value.

Mortality and ventilator dependence in critically ill patients with ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a key pathogen associated with ventilator-associated pneumonia (VAP). Research on treatment outcomes, especially ventilator dependence, in patients with VAP caused by CRAB remains limited. METHODS: This retrospective multicenter study included ICU-admitted patients with VAP caused by CRAB. The original cohort was included as the mortality evaluation cohort. The ventilator dependence evaluation cohort included cases that survived more than 21 days after VAP and without prolonged ventilation before VAP onset. The mortality rate, ventilator dependence rate, clinical factors associated with treatment outcomes, and treatment outcome differences with various VAP onset times were investigated. RESULTS: In total, 401 patients with VAP caused by CRAB were analyzed. The 21-day all-cause mortality rate was 25.2%, and the 21-day ventilator dependence rate was 48.8%. Clinical factors associated with 21-day mortality included lower body mass index, higher sequential organ failure assessment score, vasopressors usage, CRAB persistence, and VAP onset time > seven days. Clinical factors associated with 21-day ventilator dependence included older age, vasopressors usage, and VAP onset time > seven days. CONCLUSIONS: ICU-admitted patients with CRAB-related VAP had high mortality and ventilator dependence rates. Older age, vasopressor usage, and longer VAP onset time were independent factors associated with ventilator dependence.

Ventilator-associated pneumonia in neurocritically ill patients: insights from the ENIO international prospective observational study.

BACKGROUND: Acute brain injured (ABI) patients are at high risk of developing ventilator-associated pneumonia (VAP). However, incidence, risk factors and effects on outcome of VAP are not completely elucidated in this population. The primary aim of this study was to determine the incidence of VAP in a cohort of ABI patients. The secondary objectives included the identification of risk factors for development of VAP, and the impact of VAP on clinical outcomes. Clinical outcomes were defined as intensive care unit length of stay (ICU-LOS), duration of invasive mechanical ventilation (IMV), and ICU mortality. METHODS: Pre-planned sub-analysis of the Extubation strategies in Neuro-Intensive care unit (ICU) patients and associations with Outcomes (ENIO) international multi-center prospective observational study. Patients with available data on VAP, who received at least 48 h of IMV and ICU-LOS ≥ 72 h were included. RESULTS: Out of 1512 patients included in the ENIO study, 1285 were eligible for this analysis. The prevalence of VAP was 39.5% (33.7 cases /1000 ventilator-days), with a high heterogeneity across countries and according to the type of brain injury. VAP was significantly more frequent in male patients, in those with smoke habits and when intraparenchymal probe (IP), external ventricular drain (EVD) or hypothermia (p < 0.001) were used. Independent risk factors for VAP occurrence were male gender, the use of IP, hypothermia, and the occurrence of tracheobronchitis during ICU stay. VAP was not an independent risk factor for ICU mortality (Hazard Ratio, HR = 0.71 95%CI 0.43-1.16, p = 0.168), but was independently associated with longer ICU stay (OR = 2.55 95%CI 2.01-3.23, p < 0.001). CONCLUSIONS: VAP is common in ABI patients. Male gender, IP and EVD insertion, tracheobronchitis, and the use of therapeutic hypothermia were significantly associated with VAP occurrence. VAP did not affect mortality but increased ICU-LOS.

Risk factors for developing ventilator-associated lower respiratory tract infection in patients with severe COVID-19: a multinational, multicentre study, prospective, observational study.

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287], followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% [266/1252]), followed by Klebsiella pneumoniae (19.1% [239/1252]) and Staphylococcus aureus (15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40-2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98-1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes.Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

Interventions Relieving Dyspnea in Intubated Patients Show Responsiveness of the Mechanical Ventilation-Respiratory Distress Observation Scale.

Rationale: Breathing difficulties are highly stressful. In critically ill patients, they are associated with an increased risk of posttraumatic manifestations. Dyspnea, the corresponding symptom, cannot be directly assessed in noncommunicative patients. This difficulty can be circumvented using observation scales such as the mechanical ventilation-respiratory distress observation scale (MV-RDOS). Objective: To investigate the performance and responsiveness of the MV-RDOS to infer dyspnea in noncommunicative intubated patients. Methods: Communicative and noncommunicative patients exhibiting breathing difficulties under mechanical ventilation were prospectively included and assessed using a dyspnea visual analog scale, MV-RDOS, EMG activity of alae nasi and parasternal intercostals, and EEG signatures of respiratory-related cortical activation (preinspiratory potentials). Inspiratory-muscle EMG and preinspiratory cortical activities are surrogates of dyspnea. Assessments were conducted at baseline, after adjustment of ventilator settings, and, in some cases, after morphine administration. Measurements and Main Results: Fifty patients (age, 67 [(interquartile interval [IQR]), 61-76] yr; Simplified Acute Physiology Score II, 52 [IQR, 35-62]) were included, 25 of whom were noncommunicative. Relief occurred in 25 (50%) patients after ventilator adjustments and in 21 additional patients after morphine administration. In noncommunicative patients, MV-RDOS score decreased from 5.5 (IQR, 4.2-6.6) at baseline to 4.2 (IQR, 2.1-4.7; P < 0.001) after ventilator adjustments and 2.5 (IQR, 2.1-4.2; P = 0.024) after morphine administration. MV-RDOS and alae nasi/parasternal EMG activities were positively correlated (ρ = 0.41 and 0.37, respectively). MV-RDOS scores were higher in patients with EEG preinspiratory potentials (4.9 [IQR, 4.2-6.3] vs. 4.0 [IQR, 2.1-4.9]; P = 0.002). Conclusions: The MV-RDOS seems able to detect and monitor respiratory symptoms reasonably well in noncommunicative intubated patients. Clinical trial registered with www.clinicaltrials.gov (NCT02801838).

Respiratory Monitoring During Mechanical Ventilation: The Present and the Future.

The increased application of mechanical ventilation, the recognition of its harms and the interest in individualization raised the need for an effective monitoring. An increasing number of monitoring tools and modalities were introduced over the past 2 decades with growing insight into asynchrony, lung and chest wall mechanics, respiratory effort and drive. They should be used in a complementary rather than a standalone way. A sound strategy can guide a reduction in adverse effects like ventilator-induced lung injury, ventilator-induced diaphragm dysfunction, patient-ventilator asynchrony and helps early weaning from the ventilator. However, the diversity, complexity, lack of expertise, and associated cost make formulating the appropriate monitoring strategy a challenge for clinicians. Most often, a big amount of data is fed to the clinicians making interpretation difficult. Therefore, it is fundamental for intensivists to be aware of the principle, advantages, and limits of each tool. This analytic review includes a simplified narrative of the commonly used basic and advanced respiratory monitors along with their limits and future prospective.

Supporting all breaths versus supporting some breaths during synchronised mechanical ventilation in neonates: a systematic review and meta-analysis.

BACKGROUND: National Institute for Health and Clinical Effectiveness (NICE), UK, guideline published in 2019 recommends the use of volume-targeted ventilation (VTV). It recommends synchronised intermittent mandatory ventilation (SIMV) over the modes that support-all-breaths, for example, assist control ventilation (ACV). We conducted a systematic review and meta-analysis of the studies comparing SIMV mode with triggered modes supporting all breaths. METHODS: Patients: Neonates receiving mechanical ventilation. INTERVENTION: SIMV ventilation.Comparison: Modes that support-all-breaths: ACV, pressure support ventilation and neurally adjusted ventilation. OUTCOMES: Death before discharge and bronchopulmonary dysplasia (BPD) at 36 weeks' corrected gestation, weaning duration, incidence of air leaks, extubation failure, postnatal steroid use, patent ductus arteriosus requiring treatment, severe (grade 3/4) intraventricular haemorrhage, periventricular leukomalacia and neurodevelopmental outcome at 2 years.Randomised or quasi-randomised clinical trials comparing SIMV with triggered ventilation modes supporting all breaths in neonates, reporting on at least one outcome of interest were eligible for inclusion in the review. RESULTS: Seven publications describing eight studies fulfilled the eligibility criteria. No significant difference in mortality (OR 0.74, 95% CI 0.32 to 1.74) or BPD at 36 weeks (OR 0.63, 95% CI 0.33 to 1.24), but the weaning duration was significantly shorter in support-all-breaths group with a mean difference of -22.67 hours (95% CI -44.33 to -1.01). No difference in any other outcomes. CONCLUSION: Compared with SIMV, synchronised modes supporting all breaths are associated with a shorter weaning duration with no statistically significant difference in mortality, BPD at 36 weeks or other outcomes. Larger studies with explicit ventilator and weaning protocols are needed to compare these modes in the current neonatal population. PROSPERO REGISTRATION NUMBER: The review was prospectively registered with PROSPERO: CRD42020207601.

Pneumothorax in patients with COPD and emphysema receiving home chronic non-invasive ventilation: is it the emphysema phenotype or ventilator setting?

We describe three patients with chronic obstructive pulmonary disease (COPD) and emphysema who developed a pneumothorax while receiving chronic home non-invasive ventilation (NIV). These cases raise the question whether the high alveolar pressures given by NIV may have contributed to the development of their pneumothorax by barotrauma. Pneumothorax in patients with COPD receiving NIV is uncommon, the pressures in our patients with COPD who developed pneumothorax were not extremely high and time to development of pneumothorax was relatively long after the initiation of NIV. Further, in our patients, the CT scan showed paraseptal emphysema, a known risk factor for pneumothorax. This suggests that COPD/emphysema phenotype is probably a more important factor for indicating pneumothorax risk than ventilator settings. Better phenotyping of patients with COPD in whom benefits of NIV can be expected at minimal risk of serious side-effects is needed to inform our patients properly and bring the field of chronic NIV in COPD forward.

Pattern of disease and determinants of mortality among ICU patients on mechanical ventilator in Sub-Saharan Africa: a multilevel analysis.

BACKGROUND: The global mortality rate of patients with MV is very high, despite a significant variation worldwide. Previous studies conducted in Sub-Saharan Africa among ICU patients focused on the pattern of admission and the incidence of mortality. However, the body of evidence on the clinical outcomes among patients with MV is still uncertain. OBJECTIVE: The objective of this study was to investigate the pattern of disease and determinants of mortality among patients receiving mechanical ventilation in Southern Ethiopia. METHODS: Six hundred and thirty patients on mechanical ventilation were followed for 28 days, and multilevel analysis was used to account for the clustering effect of ICU care in the region. RESULTS: The incidence of 28-day mortality among patients with MV was 49% (95% CI: 36-58). The multilevel multivariate analysis revealed that being diabetic, having GSC < 8, and night time admission (AOR = 7.4; 95% CI: 2.96-18.38), (AOR = 5.9; (5% CI: 3.23, 10.69), and (AOR = 2.5; 95% CI: 1.24, 5.05) were predictors. CONCLUSION: The higher 28-day mortality among ICU patients on mechanical ventilation in our study might be attributed to factors such as delayed patient presentation, lack of resources, insufficient healthcare infrastructure, lack of trained staff, and financial constraints. TRIAL REGISTRATION: The protocol was registered retrospectively on ( NCT05303831 ).

State-of-the-Art Opinion Article on Ventilator-Induced Diaphragm Dysfunction: Update on Diagnosis, Clinical Course, and Future Treatment Options.

Evidence from both animal and human studies now supports the development of ventilator-induced diaphragm dysfunction (VIDD) starting as early as 24 h after initiation of mechanical ventilation in the intensive care unit (ICU). However, although the concept of VIDD is now widely accepted, there remain several unanswered questions regarding its pathophysiology, rate of development, and (potentially) recovery after mechanical ventilation.This state-of-the-art opinion article briefly explains VIDD and provides an update on its clinical and prognostic relevance. It then focusses on state-of-the-art diagnostic approaches to determine diaphragm function, strength, and control (neural and peripheral), highlights knowledge gaps relevant to VIDD, and discusses the use of diaphragm pacing for VIDD prevention. It is suggested that future research projects in mechanically ventilated patients would ideally use both cortical and cervical phrenic nerve stimulation studies over time (including also diaphragm electromyography) as the gold standard techniques. This approach has not yet been utilized in a longitudinally designed study in the ICU. Application of these gold standard techniques would allow better understanding of the true pathophysiology and rate of development of VIDD. Notably, these techniques would be superior to diaphragm ultrasound, which yields surrogate markers of diaphragm function only without any direct measure of diaphragm strength or control. It is also suggested that such translational research would further advance understanding of diaphragm pacing as a very promising treatment option for VIDD.

Changes in the epidemiology of ventilator-associated events over the course of the coronavirus disease 2019 (COVID-19) pandemic.

Management of critically ill coronavirus disease 2019 (COVID-19) patients has evolved considerably during the pandemic. We investigated rates and causes of ventilator-associated events (VAEs) in COVID-19 patients in the late versus early waves in 4 Massachusetts hospitals. VAE rates per episode decreased, rates per ventilator day were stable, and most cases were caused by acute respiratory distress syndrome (ARDS).

Epidemiology and outcomes of ventilator-associated events in critically ill children: Evaluation of three different definitions.

OBJECTIVE: Ventilator-associated pneumonia (VAP) is one of the most common healthcare-associated infections in pediatric intensive care units (PICUs), but its definite diagnosis remains controversial. The CDC Ventilator-Associated Event (VAE) module (validated in adults) constitutes a new approach for VAP surveillance. DESIGN: We described epidemiological characteristics of PICU VAE cases, investigated possible risk factors, and evaluated 3 different sets of diagnostic VAE criteria. SETTING: This study was conducted in a PICU in a tertiary-care general hospital in northern Greece during 2017-2019. PATIENTS: The study included patients aged 35 days-16 years who received mechanical ventilation. METHODS: From medical records, we retrieved epidemiological data, clinical data, and laboratory characteristics as well as ventilator settings for our analysis. We assessed "oxygen deterioration" for the tier 1 CDC VAE module using 3 sets of diagnostic criteria: (1) CDC adult VAE criteria [increase of daily minimum fraction of inspired oxygen (FiO2) ≥ 0.2 or positive end expiratory pressure (PEEP) ≥ 3 cmH2O for 2 days], (2) the US pediatric VAE criteria [increase of FiO2 ≥ 0.25 or mean airway pressure (MAP) ≥ 4 cmH2O for 2 days], and (3) the European pediatric VAE criteria (increase of FiO2 ≥ 0.2 or PEEP ≥ 2 cmH2O for 1 day or increase of FiO2 ≥ 0.15 and PEEP ≥ 1 cm H2O for 1 day). RESULTS: Among 326 children admitted to the PICU, 301 received mechanical ventilation. The incidence rate according to the CDC adult VAE criteria was 4.7 per 1,000 ventilator days. For the US pediatric VAE criteria the incidence rate was 6 per 1,000 ventilator days. For the European pediatric VAE criteria the incidence rate was 9.7 per 1,000 ventilator days. These results revealed statistically significant correlation of all 3 algorithms with adverse outcomes, including mortality. CONCLUSIONS: All VAE algorithms were associated with higher mortality rates. Our findings highlight the need for a unified pediatric VAE definition to improve preventive strategies.

Outcomes in critically ill patients after diaphragmatic stimulation on ventilator-induced diaphragmatic dysfunction: a systematic review.

INTRODUCTION: Mechanical ventilation (MV) is a lifesaving procedure for critically ill patients. Diaphragm activation and stimulation may counteract side effects, such as ventilator-induced diaphragm dysfunction (VIDD). The effects of stimulation on diaphragm atrophy and patient outcomes are reported in this systematic review. EVIDENCE ACQUISITION: Studies investigating diaphragmatic stimulation versus standard of care in critically ill patients and evaluating clinical outcomes were extracted from a Medline database last on January 23, 2023, after registration in Prospero (CRD42021259353). Selected studies included the investigation of diaphragmatic stimulation versus standard of care in critically ill patients, an evaluation of the clinical outcomes. These included muscle atrophy, VIDD, weaning failure, mortality, quality of life, ventilation time, diaphragmatic function, length of stay in the Intensive Care Unit (ICU), and length of hospital stay. All articles were independently evaluated by two reviewers according to their abstract and title and, secondly, a full texts evaluation by two independent reviewers was performed. To resolve diverging evaluations, a third reviewer was consulted to reach a final decision. Data were extracted by the reviewers following the Oxford 2011 levels of evidence guidelines and summarized accordingly. EVIDENCE SYNTHESIS: Seven studies were extracted and descriptively synthesized, since a metanalysis was not feasible. Patients undergoing diaphragm stimulation had moderate evidence of higher maximal inspiratory pressure (MIP), less atrophy, less mitochondrial respiratory dysfunction, less oxidative stress, less molecular atrophy, shorter MV time, shorter ICU length of stay, longer survival, and better SF-36 scores than control. CONCLUSIONS: Evidence of the molecular and histological benefits of diaphragmatic stimulation is limited. The results indicate positive clinical effects of diaphragm activation with a moderate level of evidence for MIP and a low level of evidence for other outcomes. Diaphragm activation could be a therapeutic solution to avoid diaphragm atrophy, accelerate weaning, shorten MV time, and counteract VIDD; however, better-powered studies are needed to increase the level of evidence.

Ten rules for optimizing ventilatory settings and targets in post-cardiac arrest patients.

Cardiac arrest (CA) is a major cause of morbidity and mortality frequently associated with neurological and systemic involvement. Supportive therapeutic strategies such as mechanical ventilation, hemodynamic settings, and temperature management have been implemented in the last decade in post-CA patients, aiming at protecting both the brain and the lungs and preventing systemic complications. A lung-protective ventilator strategy is currently the standard of care among critically ill patients since it demonstrated beneficial effects on mortality, ventilator-free days, and other clinical outcomes. The role of protective and personalized mechanical ventilation setting in patients without acute respiratory distress syndrome and after CA is becoming more evident. The individual effect of different parameters of lung-protective ventilation, including mechanical power as well as the optimal oxygen and carbon dioxide targets, on clinical outcomes is a matter of debate in post-CA patients. The management of hemodynamics and temperature in post-CA patients represents critical steps for obtaining clinical improvement. The aim of this review is to summarize and discuss current evidence on how to optimize mechanical ventilation in post-CA patients. We will provide ten tips and key insights to apply a lung-protective ventilator strategy in post-CA patients, considering the interplay between the lungs and other systems and organs, including the brain.

[Effect of closed extension tube on preventing airway leakage during artificial airway clearance].

Objective: To explore the role of closed extension tube in preventing airway leakage during artificial airway clearance. Methods: The test lung was connected with a ventilator for mechanical ventilation. The pressure parameters were set as 16/5, 20/6, 24/7, 28/8, 32/9 and 36/10 cmH2O(1 cmH2O=0.098 kPa), respectively. The circuit was connected with an open extension tube or a closed extension tube. The ventilator was set with different pressure parameters to observe the changes of airway pressure and tidal volume during airway clearance. Results: (1) The pressure parameters were set as 16/5, 20/6, 24/7, 28/8, 32/9 and 36/10 cmH2O, and the airway pressures (in cmH2O) of circuit connected with open extension tube were (15.94±0.27)/(4.81±0.04), (20.09±0.23)/(6.05±0.16), (23.89±0.41)/(6.94±0.06), (27.90±0.22)/(7.71±0.18), (31.92±0.13)/(8.74±0.12)and(35.65±0.31)/(9.72±0.07), respectively.Under the same ventilator pressure parameters, the airway pressures (in cmH2O) of circuit connected with close extension tube were (16.36±0.06)/(4.85±0.04), (20.54±0.26)/(6.44±0.12), (24.36±0.24)/(7.01±0.33), (28.69±0.25)/(8.07±0.08), (32.97±0.33)/(8.93±0.09), (37.34±0.29)/(9.75±0.08), respectively. The airway pressure of circuit connected with open extension tube was lower than that connected with closed extension tube(P<0.05);with the increase of the pressure setting of the ventilator, the difference of the airway pressure between the two extended tubes gradually increased. When the maximum inspiratory pressure of the ventilator was set 36 cmH2O, the difference reached 1.69 cmH2O. (2) The airway pressures (in cmH2O) dropped from (15.94±0.27)/(4.81±0.04), (20.09±0.23)/(6.05±0.16), (23.89±0.41)/(6.94±0.06), (27.90±0.22)/(7.71±0.18), (31.92±0.13)/(8.74±0.12), (35.65±0.31)/(9.72±0.07) to (13.42±0.4)/(3.15±0.14), (16.81±0.6)/(4.30±0.14), (20.22±0.5)/(5.48±0.45), (23.73±1.4)/(6.25±0.22), (24.78±0.7)/(7.13±0.21), (20.83±0.4)/(6.61±0.19)when the suction port of the open extension tube was opened (P<0.05);and the tidal volume (in L) also decreased from 0.328±0.004, 0.580±0.012, 0.621±0.003, 0.626±0.003, 0.615±0.003, 0.603±0.002 to 0.272±0.008, 0.416±0.051, 0.487±0.047, 0.396±0.116, 0.507±0.022, 0.508±0.079, respectively (P<0.05). The decrease of airway pressure and tidal volume gradually increased with the increase of ventilator setting pressure. When the ventilator setting parameter was 36/10 cmH2O, the decrease of airway inspiratory pressure was (14.82±0.51) cmH2O and the maximum reduction of tidal volume was (0.164±0.021)L. (3)The airway pressure (in cmH2O) was increased to(15.70±0.23)/(4.80±0.33), (19.01±0.81)/(5.71±0.34), (22.27±0.62)/(6.85±0.44), (25.35±2.09)/(7.94±0.16), (28.38±0.46)/(8.96±0.23), (33.34±0.71)/(9.71±0.25) when the suction tube was inserted from the suction port of the open extension tube in the open state, and the tidal volume (in L) was increased to 0.340±0.016, 0.563±0.020, 0.571±0.030, 0.556±0.026, 0.514±0.021, 0.512±0.031 as well.The airway pressure and tidal volume of the ventilation circuit were higher than those in the open state, but still lower than those in the closed state. Compared with the closed state of the suction port, the maximum pressure drop and tidal volume decrease were (3.53±0.46) cmH2O and (0.101±0.011) L, respectively. (4) The pressure of the ventilator was set between 16/5 cmH2O to 36/10 cmH2O. The airway pressure (in cmH2O) was decreased from (16.26±0.04)/(4.85±0.04), (20.74±0.15)/(6.42±0.11), (25.09±0.31)/(7.10±0.13), (29.38±0.24)/(8.17±0.09), (33.80±0.16)/(9.02±0.17), (37.89±0.19)/(9.83±0.07) to(16.36±0.06)/(4.85±0.04), (20.54±0.26)/(6.44±0.12), (24.36±0.24)/(7.01±0.33), (28.69±0.25)/(8.07±0.08), (32.97±0.33)/(8.93±0.09), (37.34±0.29)/(9.75±0.08), respectively during the insertion of the suction tube from the suction port of the closed extension tube, and the tidal volume (in L) was decreased from0.361±0.005, 0.592±0.003, 0.631±0.001, 0.642±0.007, 0.633±0.007, 0.626±0.08 to 0.335±0.005, 0.588±0.008, 0.631±0.002, 0.638±0.004, 0.628±0.004, 0.618±0.005.The maximum pressure change of the ventilation circuit was (0.83±0.27) cm H2O and the maximum tidal volume change was (0.008±0.006)L. The changes of airway pressure and tidal volume were significantly lower than those of ventilation circuit connected with open extension tube under the same pressure parameters. Conclusion: The connection of closed extension tube in mechanical ventilation circuit can reduce the airway leakage during artificial airway clearance, which is worthy of clinical recommendation.

Advances in Ventilator Management for Patients with Acute Respiratory Distress Syndrome.

The ventilatory care of patients with acute respiratory distress syndrome (ARDS) is evolving as our understanding of physiologic mechanisms of respiratory failure improves. Despite several decades of research, the mortality rate for ARDS remains high. Over the years, we continue to expand strategies to identify and mitigate ventilator-induced lung injury. This now includes a greater understanding of the benefits and harms associated with spontaneous breathing.

Saved by the PEEP: Resolution of Complete Unilateral Lung Collapse Secondary to Mucus Plugging With Ventilator Technique.

Bronchoscopy can be used to resolve respiratory failure caused by tenacious mucus plugs. However, emergent bronchoscopy to resolve mucus plugging is not always available in small rural hospitals around the country. We present a case in which increasing the positive end-expiratory pressure settings on the ventilator resulted in immediate improvement in patient oxygenation and imaging findings during a respiratory emergency caused by mucus plugging.