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Neuromuscular blocking agents (NMBAs) inhibit patient-initiated active breath and the risk of high tidal volumes and consequent high transpulmonary pressure swings, and minimize patient/ ventilator asynchrony in acute respiratory distress syndrome (ARDS). Minimization of volutrauma and ventilator-induced lung injury (VILI) results in a lower incidence of barotrauma, improved oxygenation and a decrease in circulating proinflammatory markers. Recent randomized clinical trials did not reveal harmful muscular effects during a short course of NMBAs. The use of NMBAs should be considered during the early phase of severe ARDS for patients to facilitate lung protective ventilation or prone positioning only after optimising mechanical ventilation and sedation. The use of NMBAs should be integrated in a global strategy including the reduction of tidal volume, the rational use of PEEP, prone positioning and the use of a ventilatory mode allowing spontaneous ventilation as soon as possible. Partial neuromuscular blockade should be evaluated in future trials.

Analyzing patient data under current mechanical ventilation (MV) management processes is essential to understand MV consequences over time and to hypothesize improvements to care. However, progress is complicated by the complexity of lung-ventilator system (LVS) interactions, patient-care and patient-ventilator heterogeneity, and a lack of classification schemes for observable behavior. Ventilator waveform data originate from patient-ventilator interactions within the LVS while care processes manage both patients and ventilator settings. This study develops a computational pipeline to segment joint waveform and care settings timeseries data into phenotypes of the data generating process. The modular framework supports many methodological choices for representing waveform data and unsupervised clustering. The pipeline is generalizable although empirical output is data- and algorithm-dependent. Applied individually to 35 ARDS patients including 8 with COVID-19, a median of 8 phenotypes capture 97% of data using naive similarity assumptions on waveform and MV settings data. Individual’s phenotypes organize around ventilator mode, PEEP, and tidal volume with additional delineation of waveform behaviors. However, dynamics are not solely driven by setting changes. Fewer than 10% of phenotype changes link to ventilator settings directly. Evaluation of phenotype heterogeneity reveals LVS dynamics that cannot be discretized into sub-phenotypes without additional data or alternate assumptions. Individual phenotypes may also be aggregated for use in scalable analysis, as behaviors in the 35 patient cohort comprise 16 cohort-scale LVS types. Further, output phenotypes compactly discretize the data for longitudinal analysis and may be optimized to resolve features of interest for specific applications.

Background Neuromuscular blockade (NMB) is a therapy for acute respiratory distress syndrome (ARDS). However, the mechanism by which NMB may improve outcome for ARDS patients remains unclear. We sought to determine whether NMB attenuates biomarkers of epithelial and endothelial lung injury and systemic inflammation in ARDS patients, and whether the association is dependent on tidal volume size and the initial degree of hypoxemia. Methods We performed a secondary analysis of patients enrolled in the ARDS network low tidal volume ventilation (ARMA) study. Our primary predictor variable was the number of days receiving NMB between study enrollment and day 3. Our primary outcome variables were the change in concentration of biomarkers of epithelial injury (serum surfactant protein-D (SP-D)), endothelial injury (von Willebrand factor (VWF)), and systemic inflammation (interleukin (IL)-8). Multivariable regression analysis was used to compare the change in biomarker concentration controlling for multiple covariates. Patients were stratified by treatment arm (12 versus 6 cm 3 /kg) and by an initial arterial oxygen tension (PaO 2 ) to fractional inspired oxygen (FiO 2 ) (P/F) ratio of 120. Results A total of 446 (49%) patients had complete SP-D, VWF, and IL-8 measurements on study enrollment and day 3. After adjusting for baseline differences, each day of NMB was associated with a decrease in SP-D (−23.7 ng/ml/day, p = 0.029), VWF (−33.5% of control/day, p = 0.015), and IL-8 (−362.6 pg/ml/day, p = 0.030) in patients with an initial P/F less than or equal to 120 and receiving low tidal volume ventilation. However, patients with a P/F ratio of greater than 120 or receiving high tidal volume ventilation had either no change or an increase in SP-D, WVF, or IL-8 concentrations. Conclusion NBM is associated with decreased biomarkers of epithelial and endothelial lung injury and systemic inflammation in ARDS patients receiving low tidal volume ventilation and those with a P/F ratio less than or equal to 120.

Background Timely initiation of physical, occupational, and speech therapy in critically ill patients is crucial to reduce morbidity and improve outcomes. Over a 5-year time interval, we sought to determine the utilization of these rehabilitation therapies in the USA. Methods We performed a retrospective cohort study utilizing a large, national administrative database including ICU patients from 591 hospitals. Patients over 18 years of age with acute respiratory failure requiring invasive mechanical ventilation within the first 2 days of hospitalization and for a duration of at least 48 h were included. Results A total of 264,137 patients received invasive mechanical ventilation for a median of 4.0 [2.0–8.0] days. Overall, patients spent a median of 5.0 [3.0–10.0] days in the ICU and 10.0 [7.0–16.0] days in the hospital. During their hospitalization, 66.5%, 41.0%, and 33.2% (95% CI = 66.3–66.7%, 40.8–41.2%, 33.0–33.4%, respectively) received physical, occupational, and speech therapy. While on mechanical ventilation, 36.2%, 29.7%, and 29.9% (95% CI = 36.0–36.4%, 29.5–29.9%, 29.7–30.1%) received physical, occupational, and speech therapy. In patients receiving therapy, their first physical therapy session occurred on hospital day 5 [3.0–8.0] and hospital day 6 [4.0–10.0] for occupational and speech therapy. Of all patients, 28.6% (95% CI = 28.4–28.8%) did not receive physical, occupational, or speech therapy during their hospitalization. In a multivariate analysis, patients cared for in the Midwest and at teaching hospitals were more likely to receive physical, occupational, and speech therapy (all P  < 0.05). Of patients with identical covariates receiving therapy, there was a median of 61%, 187%, and 70% greater odds of receiving physical, occupational, and speech therapy, respectively, at one randomly selected hospital compared with another (median odds ratio 1.61, 2.87, 1.70, respectively). Conclusions Physical, occupational, and speech therapy are not routinely delivered to critically ill patients, particularly while on mechanical ventilation in the USA. The utilization of these therapies varies according to insurance coverage, geography, and hospital teaching status, and at a hospital level.

Mortality associated with the acute respiratory distress syndrome remains unacceptably high due in part to ventilator-induced lung injury (VILI). Ventilator dyssynchrony is defined as the inappropriate timing and delivery of a mechanical breath in response to patient effort and may cause VILI. Such deleterious patient-ventilator interactions have recently been termed patient self-inflicted lung injury. This narrative review outlines the detection and frequency of several different types of ventilator dyssynchrony, delineates the different mechanisms by which ventilator dyssynchrony may propagate VILI, and reviews the potential clinical impact of ventilator dyssynchrony. Until recently, identifying ventilator dyssynchrony required the manual interpretation of ventilator pressure and flow waveforms. However, computerized interpretation of ventilator waive forms can detect ventilator dyssynchrony with an area under the receiver operating curve of >0.80. Using such algorithms, ventilator dyssynchrony occurs in 3%-34% of all breaths, depending on the patient population. Moreover, two types of ventilator dyssynchrony, double-triggered and flow-limited breaths, are associated with the more frequent delivery of large tidal volumes >10 mL/kg when compared with synchronous breaths (54% [95% confidence interval (CI), 47%-61%] and 11% [95% CI, 7%-15%]) compared with 0.9% (95% CI, 0.0%-1.9%), suggesting a role in propagating VILI. Finally, a recent study associated frequent dyssynchrony-defined as >10% of all breaths-with an increase in hospital mortality (67 vs. 23%, P = 0.04). However, the clinical significance of ventilator dyssynchrony remains an area of active investigation and more research is needed to guide optimal ventilator dyssynchrony management.

Patient and family member perceptions of physical therapy (PT) in the intensive care unit and the factors that influence their degree of satisfaction have not been described. A panel of experts developed a questionnaire that assessed patient and family perceptions of PT. Critically ill patients and their family members were asked to complete the survey. Patient and family member scores were compared and stratified by age, sex, and mechanical ventilation for greater than 14 days compared to 14 days or less. A total of 55 patients and 49 family members completed the survey. Patients and family members reported that PT was necessary and beneficial to recovery, despite associating PT with difficulty, exertion, and discomfort. Patient perceptions were similar regardless of age or sex. Family members underestimated a patient's enjoyment of PT (P = .03). For individuals who required prolonged mechanical ventilation (>14 days), patients reported that PT was more difficult (P = .03) and less enjoyable (P = .049), and family members reported PT as causing greater discomfort (P = .005). In addition, family members of patients who required prolonged mechanical ventilation felt that PT was less beneficial (P = .01). Physical therapy is perceived as necessary and beneficial to recovery by critically ill patients and family members.

The neuromuscular blocking agent cisatracurium may improve mortality for patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Other neuromuscular blocking agents, such as vecuronium, are commonly used and have different mechanisms of action, side effects, cost, and availability in the setting of drug shortages. To determine whether cisatracurium is associated with improved outcomes when compared with vecuronium in patients at risk for and with ARDS. Using a nationally representative database, patients who were admitted to the ICU with a diagnosis of ARDS or an ARDS risk factor, received mechanical ventilation, and were treated with a continuous infusion of neuromuscular blocking agent for at least 2 days within 2 days of hospital admission were included. Patients were stratified into two groups: those who received cisatracurium or vecuronium. Propensity matching was used to balance both patient- and hospital-specific factors. Outcomes included hospital mortality, duration of mechanical ventilation, ICU and hospital duration, and discharge location. Propensity matching successfully balanced all covariates for 3,802 patients (1,901 per group). There was no significant difference in mortality (odds ratio, 0.932; P = 0.40) or hospital days (-0.66 d; P = 0.411) between groups. However, patients treated with cisatracurium had fewer ventilator days (-1.01 d; P = 0.005) and ICU days (-0.98 d; P = 0.028) but were equally likely to be discharged home (odds ratio, 1.19; P = 0.056). When compared with vecuronium, cisatracurium was not associated with a difference in mortality but was associated with improvements in other clinically important outcomes. These data suggest that cisatracurium may be the preferred neuromuscular blocking agent for patients at risk for and with ARDS.

Although studies have established the safety and feasibility of physical therapy in the critical care setting, minimal information about physical therapist practice in the neurological intensive care unit (NICU) is available. This study describes physical therapists' treatment of people admitted to a NICU. People admitted to the NICU with a diagnosis of subarachnoid hemorrhage, subdural hematoma, intracranial hemorrhage, or trauma were retrospectively studied. Data on patient demographics, use of mechanical ventilation, and intracranial pressure (ICP) monitoring were collected. For each physical therapy session, the length of the session, the location (NICU or post-NICU setting), and the presence of mechanical ventilation or ICP monitoring were recorded. Data on safety parameters, including vital sign response, falls, and dislodgement of lines, were collected. Over 1 year, 180 people were admitted to the NICU; 86 were evaluated by a physical therapist, for a total of 293 physical therapy sessions in the NICU (n=132) or post-NICU setting (n=161). Only one session (0.3%) was stopped, secondary to an increase in ICP. The first physical therapy session occurred on NICU day 3.0 (25%-75% interquartile range=2.0-6.0). Patients received a median of 3.4 sessions per week (25%-75% interquartile range=1.8-5.9). Patients with mechanical ventilation received less frequent physical therapy sessions than those without mechanical ventilation. Patients with ICP monitoring received less frequent sessions than those without ICP monitoring. However, after multivariate analysis, only the admission Glasgow Coma Score was independently associated with physical therapy frequency in the NICU. Patients were more likely to stand, transfer, and walk in the post-NICU setting than in the NICU. The results are limited by the retrospective, single-center nature of the study. There is inherent bias of evaluating only those patients who had physical therapy, and therapists were unable to completely adjust for the severity of illness of a given patient. Physical therapy was performed safely in the NICU. Patients who required invasive support received less frequent physical therapy.

Motivated by desire to understand pulmonary physiology and pathophysiology, scientists have developed models of pulmonary physiology. However, pathophysiology and interactions between human lungs and ventilators, e.g., ventilator-induced lung injury (VILI), present problems for modeling efforts. Real-world injury is too complex for simple models to capture, and while complex models tend not to be estimable with clinical data, limiting both the clinical utility with existing approaches. To address this gap, we present a damaged-informed lung ventilator (DILV) model to model and quantify patient-ventilator interactions and lung health. This approach relies on systematically mathematizing the pathophysiologic knowledge clinicians use to interpret lung condition from ventilator waveform data. This is achieved by defining clinically relevant features in the ventilator waveform data that contain hypothesis-driven information about pulmonary physiology, patient-ventilator interaction, and ventilator settings. To capture these features, we develop a modelling framework where the model has enough flexibility to reproduce commonly observed variability in waveform data. We infer the model parameters with clinical (human) and laboratory (mouse) data. The DILV model can reproduce essential dynamics of differently damaged lungs for tightly controlled measurements in mice and uncontrolled human intensive care unit data in the absence and presence of respiratory effort. Estimated parameters correlate with known measures of lung physiology, including lung compliance. This method has the potential to translate laboratory physiology experiments to clinical applications, including pathways for high fidelity estimates of lung state and sources of VILI with an end goal of reducing the impact of VILI and acute respiratory distress syndrome. Competing Interest Statement The authors have declared no competing interest. Footnotes * Additional model verification has been added.