Implications of uremic cardiomyopathy for the practicing clinician: an educational review.

Studies over recent years have redeveloped our understanding of uremic cardiomyopathy, defined as left ventricular hypertrophy, congestive heart failure, and associated cardiac hypertrophy plus other abnormalities that result from chronic kidney disease and are often the cause of death in affected patients. Definitions of uremic cardiomyopathy have conflicted and overlapped over the decades, complicating the body of published evidence, and making comparison difficult. New and continuing research into potential risk factors, including uremic toxins, anemia, hypervolemia, oxidative stress, inflammation, and insulin resistance, indicates the increasing interest in illuminating the pathways that lead to UC and thereby identifying potential targets for intervention. Indeed, our developing understanding of the mechanisms of UC has opened new frontiers in research, promising novel approaches to diagnosis, prognosis, treatment, and management. This educational review highlights advances in the field of uremic cardiomyopathy and how they may become applicable in practice by clinicians. Pathways to optimal treatment with current modalities (with hemodialysis and angiotensin-converting enzyme inhibitors) will be described, along with proposed steps to be taken in research to allow evidence-based integration of developing investigational therapies.

Abnormal magnesium levels and their impact on death and acute kidney injury in critically ill children.

BACKGROUND: The prevalence of magnesium imbalance in critically ill children is very high. However, its significance in the development of acute kidney injury (AKI) and mortality remains unknown. METHODS: In this retrospective observational study from 2010 to 2018, the pediatric-specific intensive care database was analyzed. We included critically ill children aged > 3 months and those without chronic kidney disease. Patients were diagnosed with AKI, according to the Kidney Disease Improving Global Outcomes (KDIGO) study. We calculated the initial corrected magnesium levels (cMg) within 24 h and used a spline regression model to evaluate the cut-off values for cMg. We analyzed 28-day mortality and its association with AKI. The interaction between AKI and magnesium imbalance was evaluated. RESULTS: The study included 3,669 children, of whom 105 died within 28 days, while 1,823 were diagnosed with AKI. The cut-off values for cMg were 0.72 and 0.94 mmol/L. Both hypermagnesemia and hypomagnesemia were associated with 28-day mortality (odds ratio [OR] = 2.99, 95% confidence interval [CI] = 1.89-4.71, p < 0.001; OR = 2.80, 95% CI = 1.60-4.89, p < 0.001). Hypermagnesemia was associated with AKI (OR = 1.52, 95% CI = 1.27-1.82, p < 0.001), while neither hypermagnesemia nor hypomagnesemia interacted with the AKI stage on the 28-day mortality. CONCLUSIONS: Abnormal magnesium levels were associated with 28-day mortality in critically ill children. AKI and hypermagnesemia had a strong association. "A higher resolution version of the Graphical abstract is available as Supplementary information".

The protective effect of tight-fitting powered air-purifying respirators during chest compressions.

BACKGROUND: Airborne personal protective equipment is required for healthcare workers when performing aerosol-generating procedures on patients with infectious diseases. Chest compressions, one of the main components of cardiopulmonary resuscitation, require intense and dynamic movements of the upper body. We aimed to investigate the protective effect of tight-fitting powered air-purifying respirators (PAPRs) during chest compressions. METHODS: This single-center simulation study was performed from February 2021 to March 2021. The simulated workplace protection factor (SWPF) is the concentration ratio of ambient particles and particles inside the PAPR mask; this value indicates the level of protection provided by a respirator when subjected to a simulated work environment. Participants performed continuous chest compressions three times for 2 min each time, with a 4-min break between each session. We measured the SWPF of the tight-fitting PAPR during chest compression in real-time mode. The primary outcome was the ratio of any failure of protection (SWPF <500) during the chest compression sessions. RESULTS: Fifty-four participants completed the simulation. Overall, 78% (n = 42) of the participants failed (the measured SWPF value was less than 500) at least one of the three sessions of chest compressions. The median value and interquartile range of the SWPF was 4304 (685-16,191). There were no reports of slipping down of the respirator or mechanical failure during chest compressions. CONCLUSIONS: Although the median SWPF value was high during chest compressions, the tight-fitting PAPR did not provide adequate protection.

Maximum Norepinephrine Dosage Within 24 Hours as an Indicator of Refractory Septic Shock: A Retrospective Study.

BACKGROUND: The management of refractory septic shock remains a major challenge in critical care and its early indicators are not fully understood. We hypothesized that the maximum norepinephrine dosage within 24 hours of intensive care unit (ICU) admission may be a useful indicator of early mortality in patients with septic shock. METHODS: In this retrospective single-center observational study, patients with septic shock admitted to the emergency ICU of an academic medical center between April 2011 and March 2017 were included. Individuals with cardiac arrest and those with do-not-resuscitate orders before admission were excluded. We analyzed if the maximum norepinephrine dosage within 24 hours of ICU admission (MD24) was associated with 7-day mortality. RESULTS: Among 152 patients with septic shock, 20 (15%) did not survive by day 7. The receiver operating characteristic curve analysis for predicting 7-day mortality revealed a cutoff of MD24 of 0.6 µg/kg/min (sensitivity 47%, specificity 93%). In the multivariable regression analysis, a higher MD24 was significantly associated with 7-day mortality (odds ratio: 7.20; 95% confidence interval [CI]: 2.02-25.7; P = .002) but not with 30-day mortality. Using the inverse probability of treatment weighting method in a propensity scoring analysis, a higher MD24 was significantly associated with 7-day (hazard ratio [HR]: 8.9; 95% CI: 3.2-25.0; P < .001) and 30-day mortality (HR: 2.7; 95% CI: 1.2-5.8; P = .012). CONCLUSIONS: An MD24 ≥0.6 µg/kg/min was significantly associated with 7-day mortality in patients with septic shock and may therefore be a useful indicator of refractory septic shock.

Clinical implications of septic cardiomyopathy: A narrative review.

Sepsis is caused by the body's dysregulated response to infection, which can lead to multiorgan injury and death. Patients with sepsis may develop acute cardiac dysfunction, termed septic cardiomyopathy, which is a global but reversible dysfunction of both sides of the heart. This narrative review discusses the mechanistic changes in the heart during septic cardiomyopathy, its diagnosis, existing treatment options regarding severity and course, and emerging treatment approaches. Although no standardized definition for septic cardiomyopathy exists, it is described as a reversible myocardial dysfunction that typically resolves within 7 to 10 days. Septic cardiomyopathy is often diagnosed based on electrocardiography, cardiac magnetic resonance imaging, biomarkers, and direct invasive and noninvasive measures of cardiac output. Presently, the treatment of septic cardiomyopathy is similar to that of sepsis, primarily focusing on acute interventions. Treatments for cardiomyopathy often include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics. However, because of profound hypotension in sepsis, many cardiomyopathy treatments are contraindicated in patients with septic cardiomyopathy. Substantial efforts have been made to study the pathophysiological mechanisms and diagnostic options; however, the lack of a uniform definition for septic cardiomyopathy is challenging for physicians when considering treatments. Another challenge for physicians is that the treatment for septic cardiomyopathy has only focused on acute intervention, whereas the treatment for other cardiomyopathies has been provided on a long-term basis. A better understanding of the underlying mechanisms of septic cardiomyopathy may contribute to the development of a unified definition of the condition and novel treatment options.

Effects of acute phase intensive electrical muscle stimulation in COVID-19 patients requiring invasive mechanical ventilation: an observational case-control study.

We investigated the effects of acute-phase intensive electrical muscle stimulation (EMS) on physical function in COVID-19 patients with respiratory failure requiring invasive mechanical ventilation (IMV) in the intensive care unit (ICU). Consecutive COVID-19 patients requiring IMV admitted to a university hospital ICU between January and April 2022 (EMS therapy group) or between March and September 2021 (age-matched historical control group) were included in this retrospective observational case-control study. EMS was applied to both upper and lower limb muscles for up to 2 weeks in the EMS therapy group. The study population consisted of 16 patients undergoing EMS therapy and 16 age-matched historical controls (median age, 71 years; 81.2% male). The mean period until initiation of EMS therapy after ICU admission was 3.2 ± 1.4 days. The EMS therapy group completed a mean of 6.2 ± 3.7 EMS sessions, and no adverse events occurred. There were no significant differences between the two groups in Medical Research Council sum score (51 vs. 53 points, respectively; P = 0.439) or ICU mobility scale at ICU discharge. Addition of upper and lower limb muscle EMS therapy to an early rehabilitation program did not result in improved physical function at ICU discharge in severe COVID-19 patients.

Association between loss of hypercoagulable phenotype, clinical features and complement pathway consumption in COVID-19.

Background: Coronavirus disease 2019 (COVID-19) features a hypercoagulable state, but therapeutic anticoagulation effectiveness varies with disease severity. We aimed to evaluate the dynamics of the coagulation profile and its association with COVID-19 severity, outcomes, and biomarker trajectories. Methods: This multicenter, prospective, observational study included patients with COVID-19 requiring respiratory support. Rotational thromboelastometry findings were evaluated for coagulation and fibrinolysis status. Hypercoagulable status was defined as supranormal range of maximum clot elasticity in an external pathway. Longitudinal laboratory parameters were collected to characterize the coagulation phenotype. Results: Of 166 patients, 90 (54%) were severely ill at inclusion (invasive mechanical ventilation, 84; extracorporeal membrane oxygenation, 6). Higher maximum elasticity (P=0.02) and lower maximum lysis in the external pathway (P=0.03) were observed in severely ill patients compared with the corresponding values in patients on non-invasive oxygen supplementation. Hypercoagulability components correlated with platelet and fibrinogen levels. Hypercoagulable phenotype was associated with favorable outcomes in severely ill patients, while normocoagulable phenotype was not (median time to recovery, 15 days vs. 27 days, P=0.002), but no significant association was observed in moderately ill patients. In patients with severe COVID-19, lower initial C3, minimum C3, CH50, and greater changes in CH50 were associated with the normocoagulable phenotype. Changes in complement components correlated with dynamics of coagulation markers, hematocrit, and alveolar injury markers. Conclusions: While hypercoagulable states become more evident with increasing severity of respiratory disease in patients with COVID-19, normocoagulable phenotype is associated with triggered by alternative pathway activation and poor outcomes.

Challenges hindering emergency physicians; involvement in multicenter collaborative studies in Japan: A nationwide survey analysis.

Aim: Multicenter collaborative research accelerates patient recruitment and strengthens evidence. Nevertheless, the factors influencing emergency and critical care physicians' involvement in such research in Japan remain unclear. Methods: A nationwide web-based survey conducted in early 2023 targeted emergency physicians working a minimum of 3 days per week in Japan. The survey descriptively assessed their backgrounds, work and research environments, experiences, and perceived impediments and motivators for multicenter research. Results: Of the 387 respondents, 348 were included in the study, yielding a 5.1% response rate. Women comprised 11% of the participants; 33% worked in university hospitals, 65% served in both emergency departments and intensive care units, and 54% did shift work. Only 12% had designated research time during working hours, with a median of 1 hour per week (interquartile range 0-5 h), including time outside of work. While 73% had participated in multicenter research, 58% noted barriers to participation. The key obstacles were excessive data entry (72%), meeting time constraints (59%), ethical review at each facility (50%), and unique sample collection, such as bronchoalveolar lavage specimens or pathological tissues (51%). The major incentives were networking (70%), data sets reuse (65%), feedback on research results (63%), and recognition from academic societies (63%). Financial rewards were not highly prioritized (38%). Conclusions: While valuing clinical research, emergency physicians face barriers, especially data entry burden and limited research time. Networking and sharing research findings motivate them. These insights can guide strategies to enhance collaborative research in emergency and critical care in Japan.

The Accuracy and Potential Racial and Ethnic Biases of GPT-4 in the Diagnosis and Triage of Health Conditions: Evaluation Study.

BACKGROUND: Whether GPT-4, the conversational artificial intelligence, can accurately diagnose and triage health conditions and whether it presents racial and ethnic biases in its decisions remain unclear. OBJECTIVE: We aim to assess the accuracy of GPT-4 in the diagnosis and triage of health conditions and whether its performance varies by patient race and ethnicity. METHODS: We compared the performance of GPT-4 and physicians, using 45 typical clinical vignettes, each with a correct diagnosis and triage level, in February and March 2023. For each of the 45 clinical vignettes, GPT-4 and 3 board-certified physicians provided the most likely primary diagnosis and triage level (emergency, nonemergency, or self-care). Independent reviewers evaluated the diagnoses as "correct" or "incorrect." Physician diagnosis was defined as the consensus of the 3 physicians. We evaluated whether the performance of GPT-4 varies by patient race and ethnicity, by adding the information on patient race and ethnicity to the clinical vignettes. RESULTS: The accuracy of diagnosis was comparable between GPT-4 and physicians (the percentage of correct diagnosis was 97.8% (44/45; 95% CI 88.2%-99.9%) for GPT-4 and 91.1% (41/45; 95% CI 78.8%-97.5%) for physicians; P=.38). GPT-4 provided appropriate reasoning for 97.8% (44/45) of the vignettes. The appropriateness of triage was comparable between GPT-4 and physicians (GPT-4: 30/45, 66.7%; 95% CI 51.0%-80.0%; physicians: 30/45, 66.7%; 95% CI 51.0%-80.0%; P=.99). The performance of GPT-4 in diagnosing health conditions did not vary among different races and ethnicities (Black, White, Asian, and Hispanic), with an accuracy of 100% (95% CI 78.2%-100%). P values, compared to the GPT-4 output without incorporating race and ethnicity information, were all .99. The accuracy of triage was not significantly different even if patients' race and ethnicity information was added. The accuracy of triage was 62.2% (95% CI 46.5%-76.2%; P=.50) for Black patients; 66.7% (95% CI 51.0%-80.0%; P=.99) for White patients; 66.7% (95% CI 51.0%-80.0%; P=.99) for Asian patients, and 62.2% (95% CI 46.5%-76.2%; P=.69) for Hispanic patients. P values were calculated by comparing the outputs with and without conditioning on race and ethnicity. CONCLUSIONS: GPT-4's ability to diagnose and triage typical clinical vignettes was comparable to that of board-certified physicians. The performance of GPT-4 did not vary by patient race and ethnicity. These findings should be informative for health systems looking to introduce conversational artificial intelligence to improve the efficiency of patient diagnosis and triage.

Physical function and mental health trajectories in COVID-19 patients following invasive mechanical ventilation: a prospective observational study.

This prospective observational cohort study was performed to investigate the physical function and mental health trajectories of novel coronavirus disease 2019 (COVID-19) patients requiring invasive mechanical ventilation (IMV) after discharge from the intensive care unit (ICU). The study population consisted of 64 patients (median age, 60 years; 85.9% male; median IMV duration, 9 days). At ICU discharge, 28.1% of the patients had Medical Research Council (MRC) sum score < 48 points, and prolonged IMV was significantly associated with lower MRC sum score and handgrip strength. Symptoms were similar between groups at ICU discharge, and the symptoms most commonly reported as moderate-to-severe were impaired well-being (52%), anxiety (43%), tiredness (41%), and depression (35%). Although muscle strength and mobility status were significantly improved after ICU discharge, Edmonton Symptom Assessment System score did not improve significantly in the prolonged IMV group. EuroQol five-dimension five-level summary index was significantly lower in the prolonged than short IMV group at 6 months after ICU discharge. We found substantial negative physical function and mental health consequences in the majority of surviving COVID-19 patients requiring IMV, with prolonged period of IMV showing greater negative effects not only immediately but also at 6 months after discharge from the ICU.

High versus low positive end-expiratory pressure setting in patients receiving veno-venous extracorporeal membrane oxygenation support for severe acute respiratory distress syndrome: study protocol for the multicentre, randomised ExPress SAVER Trial.

INTRODUCTION: While limiting the tidal volume to 6 mL/kg during veno-venous extracorporeal membrane oxygenation (V-V ECMO) to ameliorate lung injury in patients with acute respiratory distress syndrome (ARDS) is widely accepted, the best setting for positive end-expiratory pressure (PEEP) is still controversial. This study is being conducted to investigate whether a higher PEEP setting (15 cmH2O) during V-V ECMO can decrease the duration of ECMO support needed in patients with severe ARDS, as compared with a lower PEEP setting. METHODS AND ANALYSIS: The study is an investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial conducted with the participation of 20 intensive care units (ICUs) at academic as well as non-academic hospitals in Japan. The subjects of the study are patients with severe ARDS who require V-V ECMO support. Eligible patients will be randomised equally to the high PEEP group or low PEEP group. Recruitment to the study will continue until a total of 210 patients with ARDS requiring V-V ECMO support have been randomised. In the high PEEP group, PEEP will be set at 15 cmH2O from the start of V-V ECMO until the trials for liberation from V-V ECMO (or until day 28 after the allocation), while in the low PEEP group, the PEEP will be set at 5 cmH2O. Other treatments will be the same in the two groups. The primary endpoint of the study is the number of ECMO-free days until day 28, defined as the length of time (in days) from successful libration from V-V ECMO to day 28. The secondary endpoints are mortality on day 28, in-hospital mortality on day 60, ventilator-free days during the first 60 days and length of ICU stay. ETHICS AND DISSEMINATION: Ethics approval for the trial at all the participating hospitals was obtained on 27 September 2022, by central ethics approval (IRB at Hiroshima University Hospital, C2022-0006). The results of this study will be presented at domestic and international medical congresses, and also published in scientific journals. TRIAL REGISTRATION NUMBER: The Japan Registry of Clinical Trials jRCT1062220062. Registered on 28 September 2022. PROTOCOL VERSION: 28 March 2023, version 4.0.

Recurrence of Overdose Suicide Attempt index: a novel scoring system for predicting the recurrence of intentional overdose.

Repeated suicide attempts through intentional overdose are not infrequent, but little is known about the risk factors associated with intentional overdose. We investigated these risk factors within 1 year of discharge from hospital and developed an index predicting recurrence. This retrospective observational study included 419 patients admitted to our hospital between 2011 and 2018 due to intentional overdose. Of these, 43 (10.0%) repeated an overdose within 1 year of discharge. The risk factors with the highest odds ratios from multivariate logistic regression analyses were used to develop an index assessing Recurrence of Overdose Suicide Attempt. The following variables were significantly associated with recurrence and were included in the index: anxiety and/or insomnia at discharge; use of five or more psychotropic medications; diagnosis of an ICD-F4 anxiety disorders; and female sex (odds ratios: 4.24; 5.52; 2.41; and 3.41, respectively). The area under the receiver operating characteristic curve of the index was 0.797. Sensitivity, specificity, and positive and negative predictive values for Recurrence of Overdose Suicide Attempt >4 points (out of 6) were 72.1%, 75.8%, 25.4%, and 96.0%, respectively. Our novel index predicted the recurrence of intentional overdose with a good negative predictive value and may therefore be a useful screening tool for this high-risk population.

The Contribution of Chest X-Ray to Predict Extubation Failure in Mechanically Ventilated Patients Using Machine Learning-Based Algorithms.

OBJECTIVES: To evaluate the contribution of a preextubation chest X-ray (CXR) to identify the risk of extubation failure in mechanically ventilated patients. DESIGN: Retrospective cohort study. SETTINGS: ICUs in a tertiary center (the Medical Information Mart for Intensive Care IV database). PATIENTS: Patients greater than or equal to 18 years old who were mechanically ventilated and extubated after a spontaneous breathing trial. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 1,066 mechanically ventilated patients, 132 patients (12%) experienced extubation failure, defined as reintubation or death within 48 hours of extubation. To predict extubation failure, we developed the following models based on deep learning (EfficientNet) and machine learning (LightGBM) with the training data: 1) model using only the rapid-shallow breathing index (RSBI), 2) model using RSBI and CXR, 3) model using all candidate clinical predictors (i.e., patient demographics, vital signs, laboratory values, and ventilator settings) other than CXR, and 4) model using all candidate clinical predictors with CXR. We compared the predictive abilities between models with the test data to investigate the predictive contribution of CXR. The predictive ability of the model using CXR as well as RSBI was not significantly higher than that of the model using only RSBI (c-statistics, 0.56 vs 0.56; p = 0.95). The predictive ability of the model using clinical predictors with CXR was not significantly higher than that of the model using all clinical predictors other than CXR (c-statistics, 0.71 vs 0.70; p = 0.12). Based on SHapley Additive exPlanations values to interpret the model using all clinical predictors with CXR, CXR was less likely to contribute to the predictive ability than other predictors (e.g., duration of mechanical ventilation, inability to follow commands, and heart rate). CONCLUSIONS: Adding CXR to a set of other clinical predictors in our prediction model did not significantly improve the predictive ability of extubation failure in mechanically ventilated patients.

Bedside cannulation for veno-venous extracorporeal membrane oxygenation using portable X-ray system in a coronavirus disease patient.

Transportation of patients with coronavirus disease (COVID)-19 outside isolation rooms should be avoided to prevent further spread of the disease. Here, we report a safe and accurate bedside cannulation method for veno-venous extracorporeal membrane oxygenation (VV-ECMO) in a COVID-19 patient in the intensive care unit. A 71-year-old man was admitted to our hospital and diagnosed as having COVID-19 pneumonia. We decided to initiate VV-ECMO therapy because maintaining blood oxygen saturation was difficult despite the mechanical ventilation. We placed two flat-panel detectors behind the patient's chest and the right inguinal area. We repeatedly imaged and monitored insertion of wires and cannulas using a portable X-ray system. Cannulas were successfully inserted in the appropriate position, and VV-ECMO was initiated without any complications. .

Effects of evidence-based ICU care on long-term outcomes of patients with sepsis or septic shock (ILOSS): protocol for a multicentre prospective observational cohort study in Japan.

INTRODUCTION: Sepsis is not only the leading cause of death in the intensive care unit (ICU) but also a major risk factor for physical and cognitive impairment and mental disorders, known as postintensive care syndrome (PICS), reduced health-related quality of life (HRQoL) and even mental health disorders in patient families (PICS-family; PICS-F). The ABCDEF bundle is strongly recommended to overcome them, while the association between implementing the bundle and the long-term outcomes is also unknown. METHODS AND ANALYSIS: This is a multicentre prospective observational study at 26 ICUs. All consecutive patients between 1 November 2020 and 30 April 2022, who are 18 years old or older and expected to stay in an ICU for more than 48 hours due to sepsis or septic shock, are enrolled. Follow-up to evaluate survival and PICS/ PICS-F will be performed at 3, 6 and 12 months and additionally every 6 months up to 5 years after hospital discharge. Primary outcomes include survival at 12 months, which is the primary outcome, and the incidence of PICS defined as the presence of any physical impairment, cognitive impairment or mental disorders. PICS assessment scores, HRQoL and employment status are evaluated. The association between the implementation rate for the ABCDEF bundle and for each of the individual elements and long-term outcomes will be evaluated. The PICS-F, defined as the presence of mental disorders, and HRQoL of the family is also assessed. Additional analyses with data up to 5 years follow-up are planned. ETHICS AND DISSEMINATION: This study received ethics approvals from Saiseikai Utsunomiya Hospital (2020-42) and all other participating institutions and was registered in the University Hospital Medical Information Network Clinical Trials Registry. Informed consent will be obtained from all patients. The findings will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: UMIN000041433.

Assessment of Critical Care Surge Capacity During the COVID-19 Pandemic in Japan.

Japan has the highest proportion of older adults worldwide but has fewer critical care beds than most high-income countries. Although the COVID-19 infection rate in Japan is low compared with Europe and the United States, by the end of 2020, several infected people died in ambulances because they could not find hospitals to accept them. Our study aimed to examine the Japanese healthcare system's capacity to accommodate critically ill COVID-19 patients during the pandemic. We created a model to estimate bed and staff capacity at 3 levels of pandemic response (conventional, contingency, and crisis), as defined by the US National Academy of Medicine, and the function of Japan's healthcare system at each level. We then compared our estimates of the number of COVID-19 patients requiring intensive care at peak times with the national health system capacity using expert panel data. Our findings suggest that Japan's healthcare system currently can accommodate only a limited number of critically ill COVID-19 patients. It could accommodate the surge of pandemic demands by converting nonintensive care unit beds to critical care beds and using nonintensive care unit staff for critical care. However, bed and staff capacity should not be expanded uniformly, so that the limited number of physicians and nurses are allocated efficiently and so staffing does not become the bottleneck of the expansion. Training and deploying physicians and nurses to provide immediate intensive care is essential. The key is to introduce and implement the concept and mechanism of tiered staffing in the Japanese healthcare system. More importantly, most intensive care facilities in Japanese hospitals are small-scaled and thinly distributed in each region. The government needs to introduce an efficient system for smooth dispatching of medical personnel among hospitals regardless of their founding institutions.

Relative platelet reductions provide better pathophysiologic signatures of coagulopathies in sepsis.

In sepsis-associated coagulopathies and disseminated intravascular coagulation, relative platelet reductions may reflect coagulopathy severity. However, limited evidence supports their clinical significance and most sepsis-associated coagulopathy criteria focus on the absolute platelet counts. To estimate the impact of relative platelet reductions and absolute platelet counts on sepsis outcomes. A multicenter retrospective observational study was performed using the eICU Collaborative Research Database, comprising 335 intensive care units (ICUs) in the United States. Patients with sepsis and an ICU stay > 2 days were included. Estimated effects of relative platelet reductions and absolute platelet counts on mortality and coagulopathy-related complications were evaluated. Overall, 26,176 patients were included. Multivariate mixed-effect logistic regression analysis revealed marked in-hospital mortality risk with larger platelet reductions between days one and two, independent from the resultant absolute platelet counts. The adjusted odds ratio (OR) [95% confidence intervals (CI)] for in-hospital mortality was 1.28[1.23-1.32], 1.86[1.75-1.97], 2.99[2.66-3.36], and 6.05[4.40-8.31] for 20-40%, 40-60%, 60-80%, and > 80% reductions, respectively, when compared with a < 20% decrease in platelets (P < 0.001 for each). In the multivariate logistic regression analysis, platelet reductions ≥ 11% and platelet counts ≤ 100,000/µL on day 2 were associated with high coagulopathy-related complications (OR [95%CI], 2.03 and 1.18; P < 0.001 and P < 0.001), while only platelet reduction was associated with thromboembolic complications (OR [95%CI], 1.43 [1.03-1.98], P < 0.001). The magnitude of platelet reductions represent mortality risk and provides a better signature of coagulopathies in sepsis; therefore, it is a plausible criterion for sepsis-associated coagulopathies.

Usefulness of Respiratory Mechanics and Laboratory Parameter Trends as Markers of Early Treatment Success in Mechanically Ventilated Severe Coronavirus Disease: A Single-Center Pilot Study.

Whether a patient with severe coronavirus disease (COVID-19) will be successfully liberated from mechanical ventilation (MV) early is important in the COVID-19 pandemic. This study aimed to characterize the time course of parameters and outcomes of severe COVID-19 in relation to the timing of liberation from MV. This retrospective, single-center, observational study was performed using data from mechanically ventilated COVID-19 patients admitted to the ICU between 1 March 2020 and 15 December 2020. Early liberation from ventilation (EL group) was defined as successful extubation within 10 days of MV. The trends of respiratory mechanics and laboratory data were visualized and compared between the EL and prolonged MV (PMV) groups using smoothing spline and linear mixed effect models. Of 52 admitted patients, 31 mechanically ventilated COVID-19 patients were included (EL group, 20 (69%); PMV group, 11 (31%)). The patients' median age was 71 years. While in-hospital mortality was low (6%), activities of daily living (ADL) at the time of hospital discharge were significantly impaired in the PMV group compared to the EL group (mean Barthel index (range): 30 (7.5-95) versus 2.5 (0-22.5), p = 0.048). The trends in respiratory compliance were different between patients in the EL and PMV groups. An increasing trend in the ventilatory ratio during MV until approximately 2 weeks was observed in both groups. The interaction between daily change and earlier liberation was significant in the trajectory of the thrombin-antithrombin complex, antithrombin 3, fibrinogen, C-reactive protein, lymphocyte, and positive end-expiratory pressure (PEEP) values. The indicator of physiological dead space increases during MV. The trajectory of markers of the hypercoagulation status, inflammation, and PEEP were significantly different depending on the timing of liberation from MV. These findings may provide insight into the pathophysiology of COVID-19 during treatment in the critical care setting.

Failure of non-invasive respiratory support after 6 hours from initiation is associated with ICU mortality.

A previous study has shown that late failure (> 48 hours) of high-flow nasal cannula (HFNC) was associated with intensive care unit (ICU) mortality. The aim of this study was to investigate whether failure of non-invasive respiratory support, including HFNC and non-invasive positive pressure ventilation (NPPV), was also associated with the risk of mortality even if it occurs in the earlier phase. We retrospectively analyzed 59 intubated patients for acute respiratory failure due to lung diseases between April 2014 and June 2018. We divided the patients into 2 groups according to the time from starting non-invasive ventilatory support until their intubation: ≤ 6 hours failure and > 6 hours failure group. We evaluated the differences in the ICU mortality between these two groups. The multivariate logistic regression analysis showed the highest mortality in the > 6 hours failure group as compared to the ≤ 6 hours failure group, with a statistically significant difference (p < 0.01). It was also associated with a statistically significant increased 30-day mortality and decreased ventilator weaning rate. The ICU mortality in patients with acute respiratory failure caused by lung diseases was increased if the time until failure of HFNC and NPPV was more than 6 hours.