Static Respiratory System Compliance as a Predictor of Extubation Failure in Patients with Acute Respiratory Failure.

PURPOSE: Ventilator weaning protocols rely in part on objective indices to best predict extubation failure in the critically ill. We investigated static respiratory system compliance (RC) as a predictor of extubation failure, in comparison to extubation readiness using rapid shallow breathing index (RSBI). MATERIAL AND METHODS: This was a cross-sectional, multi-institutional study of mechanically ventilated patients admitted between 12/01/2017 and 12/01/2019. All patients older than 18 years with a documented spontaneous breathing trial and extubation trial were included. RC and RSBI were calculated prior to the extubation trial. The primary outcome was extubation failure-defined as need for reintubation within 72 h from time of extubation. RESULTS: Of the 2263 patients, 55.8% were males with a mean age of 68 years. The population consisted mostly of Caucasians (73%) and African Americans (20.4%). 274 (12.1%) patients required reintubation within 72 h. On multivariate logistic regression after adjusting for age, sex, body mass index (BMI), admission Sequential Organ Failure Assessment (SOFA) score, number of ventilator days, and the P/F ratio on the day of extubation, RC remained the strongest predictor for extubation failure at 24 h (aOR 1.45; 95% CI 1.00-2.10) and 72 h (aOR 1.58; 95% CI 1.15-2.17). There was no significant association between RSBI and extubation failure at 24 (aOR 1.00; 95% CI 0.99-1.01) or at 72 h (aOR 1.00; 95% CI 0.99-1.01). CONCLUSION: RC measured on the day of extubation is a promising physiological discriminant to potentially risk stratify patients with acute respiratory failure for extubation readiness. We recommend further validation studies in prospective cohorts.

Venous thromboembolism in COVID-19 patients and prediction model: a multicenter cohort study.

BACKGROUND: Patients with COVID-19 infection are commonly reported to have an increased risk of venous thrombosis. The choice of anti-thrombotic agents and doses are currently being studied in randomized controlled trials and retrospective studies. There exists a need for individualized risk stratification of venous thromboembolism (VTE) to assist clinicians in decision-making on anticoagulation. We sought to identify the risk factors of VTE in COVID-19 patients, which could help physicians in the prevention, early identification, and management of VTE in hospitalized COVID-19 patients and improve clinical outcomes in these patients. METHOD: This is a multicenter, retrospective database of four main health systems in Southeast Michigan, United States. We compiled comprehensive data for adult COVID-19 patients who were admitted between 1st March 2020 and 31st December 2020. Four models, including the random forest, multiple logistic regression, multilinear regression, and decision trees, were built on the primary outcome of in-hospital acute deep vein thrombosis (DVT) and pulmonary embolism (PE) and tested for performance. The study also reported hospital length of stay (LOS) and intensive care unit (ICU) LOS in the VTE and the non-VTE patients. Four models were assessed using the area under the receiver operating characteristic curve and confusion matrix. RESULTS: The cohort included 3531 admissions, 3526 had discharge diagnoses, and 6.68% of patients developed acute VTE (N = 236). VTE group had a longer hospital and ICU LOS than the non-VTE group (hospital LOS 12.2 days vs. 8.8 days, p < 0.001; ICU LOS 3.8 days vs. 1.9 days, p < 0.001). 9.8% of patients in the VTE group required more advanced oxygen support, compared to 2.7% of patients in the non-VTE group (p < 0.001). Among all four models, the random forest model had the best performance. The model suggested that blood pressure, electrolytes, renal function, hepatic enzymes, and inflammatory markers were predictors for in-hospital VTE in COVID-19 patients. CONCLUSIONS: Patients with COVID-19 have a high risk for VTE, and patients who developed VTE had a prolonged hospital and ICU stay. This random forest prediction model for VTE in COVID-19 patients identifies predictors which could aid physicians in making a clinical judgment on empirical dosages of anticoagulation.

Association of anticoagulation dose and survival in hospitalized COVID-19 patients: A retrospective propensity score-weighted analysis.

BACKGROUND: Hypercoagulability may contribute to COVID-19 pathogenicity. The role of anticoagulation (AC) at therapeutic (tAC) or prophylactic doses (pAC) is unclear. OBJECTIVES: We evaluated the impact on survival of different AC doses in COVID-19 patients. METHODS: Retrospective, multi-center cohort study of consecutive COVID-19 patients hospitalized between March 13 and May 5, 2020. RESULTS: A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n = 642) required intensive care unit (ICU) stay. 60.9% received pAC (n = 2121), 28.7% received ≥3 days of tAC (n = 998), and 10.4% (n = 361) received no AC. Propensity score (PS) weighted Kaplan-Meier plot demonstrated different 25-day survival probability in the tAC and pAC groups (57.5% vs 50.7%). In a PS-weighted multivariate proportional hazards model, AC was associated with reduced risk of death at prophylactic (hazard ratio [HR] 0.35 [95% confidence interval {CI} 0.22-0.54]) and therapeutic doses (HR 0.14 [95% CI 0.05-0.23]) compared to no AC. Major bleeding occurred more frequently in tAC patients (81 [8.1%]) compared to no AC (20 [5.5%]) or pAC (46 [2.2%]) subjects. CONCLUSIONS: Higher doses of AC were associated with lower mortality in hospitalized COVID-19 patients. Prospective evaluation of efficacy and risk of AC in COVID-19 is warranted.

Initial antimicrobial management of sepsis.

Sepsis is a common consequence of infection, associated with a mortality rate > 25%. Although community-acquired sepsis is more common, hospital-acquired infection is more lethal. The most common site of infection is the lung, followed by abdominal infection, catheter-associated blood steam infection and urinary tract infection. Gram-negative sepsis is more common than gram-positive infection, but sepsis can also be due to fungal and viral pathogens. To reduce mortality, it is necessary to give immediate, empiric, broad-spectrum therapy to those with severe sepsis and/or shock, but this approach can drive antimicrobial overuse and resistance and should be accompanied by a commitment to de-escalation and antimicrobial stewardship. Biomarkers such a procalcitonin can provide decision support for antibiotic use, and may identify patients with a low likelihood of infection, and in some settings, can guide duration of antibiotic therapy. Sepsis can involve drug-resistant pathogens, and this often necessitates consideration of newer antimicrobial agents.

Extubation Failure in Critically Ill COVID-19 Patients: Risk Factors and Impact on In-Hospital Mortality.

PURPOSE: We sought to identify clinical factors that predict extubation failure (reintubation) and its prognostic implications in critically ill COVID-19 patients. MATERIALS AND METHODS: Retrospective, multi-center cohort study of hospitalized COVID-19 patients. Multivariate competing risk models were employed to explore the rate of reintubation and its determining factors. RESULTS: Two hundred eighty-one extubated patients were included (mean age, 61.0 years [±13.9]; 54.8% male). Reintubation occurred in 93 (33.1%). In multivariate analysis accounting for death, reintubation risk increased with age (hazard ratio [HR] 1.04 per 1-year increase, 95% confidence interval [CI] 1.02 -1.06), vasopressors (HR 1.84, 95% CI 1.04-3.60), renal replacement (HR 2.01, 95% CI 1.22-3.29), maximum PEEP (HR 1.07 per 1-unit increase, 95% CI 1.02 -1.12), paralytics (HR 1.48, 95% CI 1.08-2.25) and requiring more than nasal cannula immediately post-extubation (HR 2.19, 95% CI 1.37-3.50). Reintubation was associated with higher mortality (36.6% vs 2.1%; P < 0.0001) and risk of inpatient death after adjusting for multiple factors (HR 23.2, 95% CI 6.45-83.33). Prone ventilation, corticosteroids, anticoagulation, remdesivir and tocilizumab did not impact the risk of reintubation or death. CONCLUSIONS: Up to 1 in 3 critically ill COVID-19 patients required reintubation. Older age, paralytics, high PEEP, need for greater respiratory support following extubation and non-pulmonary organ failure predicted reintubation. Extubation failure strongly predicted adverse outcomes.

Using Ventilator-Associated Pneumonia Rates as a Health Care Quality Indicator: A Contentious Concept.

Pneumonia is a leading cause of hospital-acquired infections, although reported rates of ventilator-associated pneumonia (VAP) have been declining in recent years. A multifaceted infection prevention approach, using a "ventilator bundle," has been shown to reduce the frequency of VAP, while improving other patient outcomes. Because of difficulties in defining VAP, the Center for Medicare and Medicaid Service introduced a new streamlined ventilator-associated event (VAE) definition in 2013 for the surveillance of complications in mechanically ventilated patients. VAE measures are increasingly being measured by institutions in the United States in place of VAP rates and as a potential measure of the quality of intensive care unit (ICU) care. However, there is increased recognition that the streamlined definitions identify a different subset of patients than those identified by traditional VAP surveillance and that VAP prevention strategies may not impact all the causes of VAE. Also, VAP and VAE rates may not always reflect the quality of care in a given ICU, especially since patient factors, beyond the control of the hospital, may impact the rates of VAP and VAE. In this review, we discuss the issues related to VAP as a quality measure and the areas of uncertainty related to the new VAE definitions.

Year in review 2013: Critical Care--respiratory infections.

Infectious complications, particularly in the respiratory tract of critically ill patients, are related to increased mortality. Severe infection is part of a multiple system illness and female patients with severe sepsis have a worse prognosis compared to males. Kallistatin is a protective hormokine released during monocyte activation and low levels in the setting of septic shock can predict adverse outcomes. Presepsin is another biomarker that was recently evaluated and is elevated in patients with severe sepsis patients at risk of dying. The Centers for Disease Control and Prevention has introduced new definitions for identifying patients at risk of ventilator-associated complications (VACs), but several other conditions, such as pulmonary edema and acute respiratory distress syndrome, may cause VACs, and not all patients with VACs may have ventilator-associated pneumonia. New studies have suggested strategies to identify patients at risk for resistant pathogen infection and therapies that optimize efficacy, without the overuse of broad-spectrum therapy in patients with healthcare-associated pneumonia. Innovative strategies using optimized dosing of antimicrobials, maximizing the pharmacokinetic and pharmacodynamic properties of drugs in critically ill patients, and newer routes of drug delivery are being explored to combat drug-resistant pathogens. We summarize the major clinical studies on respiratory infections in critically ill patients published in 2013.

Year in review 2012: Critical Care--respiratory infections.

Over the last two decades, considerable progress has been made in the understanding of disease mechanisms and infection control strategies related to infections, particularly pneumonia, in critically ill patients. Patient-centered and preventative strategies assume paramount importance in this era of limited health-care resources, in which effective targeted therapy is required to achieve the best outcomes. Risk stratification using severity scores and inflammatory biomarkers is a promising strategy for identifying sick patients early during their hospital stay. The emergence of multidrug-resistant pathogens is becoming a major hurdle in intensive care units. Cooperation, education, and interaction between multiple disciplines in the intensive care unit are required to limit the spread of resistant pathogens and to improve care. In this review, we summarize findings from major publications over the last year in the field of respiratory infections in critically ill patients, putting an emphasis on a newer understanding of pathogenesis, use of biomarkers, and antibiotic stewardship and examining new treatment options and preventive strategies.

Impact of a structured reporting template on the quality of HRCT radiology reports for interstitial lung disease.

PURPOSE: This QI study compared the completeness of HRCT radiology reports before and after the implementation of a disease-specific structured reporting template for suspected cases of interstitial lung disease (ILD). MATERIALS AND METHODS: A pre-post study of radiology reports for HRCT of the thorax at a multicenter health system was performed. Data was collected in 6-month period intervals before (June 2019-November 2019) and after (January 2021-June 2021) the implementation of a disease-specific template. The use of the template was voluntary. The primary outcome measure was the completeness of HRCT reports graded based on the documentation of ten descriptors. The secondary outcome measure assessed which descriptor(s) improved after the intervention. RESULTS: 521 HRCT reports before and 557 HRCT reports after the intervention were reviewed. Of the 557 reports, 118 reports (21%) were created using the structured reporting template. The mean completeness score of the pre-intervention group was 9.20 (SD = 1.08) and the post-intervention group was 9.36 (SD = 1.03) with a difference of -0.155, 95% CI [-0.2822, -0.0285, p < 0.0001]. Within the post-intervention group, the mean completeness score of the unstructured reports was 9.25 (SD = 1.07) and the template reports was 9.93 (SD = 0.25) with a difference of -0.677, 95% CI [-0.7871, -0.5671, p < 0.0001]. After the intervention, the use of two descriptors improved significantly: presence of honeycombing from 78.3% to 85.1% (p < 0.0039) and technique from 90% to 96.6% (p < 0.0001). DISCUSSION: Shifting to disease-specific structured reporting for HRCT exams of suspected ILD is beneficial, as it improves the completeness of radiology reports. Further research on how to improve the voluntary uptake of a disease-specific template is needed to help increase the acceptance of structured reporting among radiologists.

Eosinophilic pneumonia associated with azacitidine in a patient with myelodysplastic syndrome.

Eosinophilic pneumonia is characterized by cough, lung infiltrates on imaging, and by the presence of eosinophils in the alveoli and pulmonary interstitium. Azacitidine, a pyramidine nucleoside analog of cytidine, is FDA approved for the treatment of various myelodysplastic syndromes. We present a case of a 76-year-old man with recently diagnosed myelodysplastic syndrome, who developed eosinophilic pneumonia after initiating therapy with azacitidine. There was clinical and radiographic improvement with cessation of the drug and treatment with prednisone. Diagnosis of drug-induced eosinophilic pneumonia is established by having a temporal relationship between onset of symptoms and initiation of therapy, bronchoalveolar lavage or lung biopsy evidence of pulmonary eosinophilia, no other explanation for the disease, and improvement upon cessation of the offending agent. Our case illustrates the need for a high index of suspicion to identify adverse pulmonary reactions associated with newly developed medications.

Risk Factors for Pneumothorax Development Following CT-Guided Core Lung Nodule Biopsy.

BACKGROUND: This study aims to correlate nodule, patient, and technical risk factors less commonly investigated in the literature with pneumothorax development during computed tomography-guided core needle lung nodule biopsy. PATIENTS AND METHODS: Retrospective data on 671 computed tomography-guided percutaneous core needle lung biopsies from 671 patients at a tertiary care center between March 2014 and August 2016. Univariate and multivariable logistic regression analyses were used to identify pneumothorax risk factors. RESULTS: The overall incidence of pneumothorax was 26.7% (n=179). Risk factors identified on univariate analysis include anterior [odds ratio (OR)=1.98; P<0.001] and lateral (OR=2.17; P=0.002) pleural surface puncture relative to posterior puncture, traversing more than one pleural surface with the biopsy needle (OR=2.35; P=0.06), patient positioning in supine (OR=2.01; P<0.001) and decubitus nodule side up (OR=2.54; P=0.001) orientation relative to decubitus nodule side down positioning, and presence of emphysema in the path of the biopsy needle (OR=3.32; P<0.001). In the multivariable analysis, the presence of emphysematous parenchyma in the path of the biopsy needle was correlated most strongly with increased odds of pneumothorax development (OR=3.03; P=0.0004). Increased body mass index (OR=0.95; P=0.001) and larger nodule width (cm; OR=0.74; P=0.02) were protective factors most strongly correlated with decreased odds of pneumothorax development. CONCLUSION: Emphysema in the needle biopsy path is most strongly associated with pneumothorax development. Increases in patient body mass index and width of the target lung nodule are most strongly associated with decreased odds of pneumothorax.

Factors influencing the total procedure time of CT-guided percutaneous core-needle biopsies of lung nodules: a retrospective analysis.

PURPOSE This study aims to investigate the factors that influence total procedure time when performing computed tomography (CT)-guided percutaneous core-needle lung biopsies. METHODS This is a cross-sectional study of 673 patients, who underwent a CT-guided percutaneous coreneedle biopsy at a tertiary care center from March 2014 to August 2016. Data on patient, nodule, and procedural factors and outcomes were collected retrospectively. Univariate linear regression and a multivariate stepwise linear regression were utilized for analysis. RESULTS Factors most strongly associated with prolonged procedure duration include 20-gauge needle use when compared with 18-gauge needle use (estimated difference in time=1.19), collecting additional core biopsies (estimated difference in time=1.10), decubitus nodule side up (DNSU; estimated difference in time=1.42), and supine positioning (estimated difference in time=1.16) relative to decubitus nodule side down positioning, and increased nodule distance from the skin surface (estimated difference in time=1.03). Increased nodule length (estimated difference in time=0.93) was associated with reductions in procedure duration. Prolonged procedure time was associated with an increased rate of pneumothorax (odds ratio (OR)=1.02; P < .0001) and decreased rate of pulmonary hemorrhage (OR=0.97; P < .0001). CONCLUSION The use of 20-gauge biopsy needle, collecting additional core biopsies, DNSU and supine positioning, smaller nodule size, and increasing nodule distance from the skin surface were associated with increased procedure time for CT-guided core needle biopsies of lung nodules. Prolonged procedure time is associated with a higher rate of pneumothorax and a lower rate of pulmonary hemorrhage.

3D-PAST: Risk Assessment Model for Predicting Venous Thromboembolism in COVID-19.

Hypercoagulability is a recognized feature in SARS-CoV-2 infection. There exists a need for a dedicated risk assessment model (RAM) that can risk-stratify hospitalized COVID-19 patients for venous thromboembolism (VTE) and guide anticoagulation. We aimed to build a simple clinical model to predict VTE in COVID-19 patients. This large-cohort, retrospective study included adult patients admitted to four hospitals with PCR-confirmed SARS-CoV-2 infection. Model training was performed on 3531 patients hospitalized between March and December 2020 and validated on 2508 patients hospitalized between January and September 2021. Diagnosis of VTE was defined as acute deep vein thrombosis (DVT) or pulmonary embolism (PE). The novel RAM was based on commonly available parameters at hospital admission. LASSO regression and logistic regression were performed, risk scores were assigned to the significant variables, and cutoffs were derived. Seven variables with assigned scores were delineated as: DVT History = 2; High D-Dimer (>500−2000 ng/mL) = 2; Very High D-Dimer (>2000 ng/mL) = 5; PE History = 2; Low Albumin (<3.5 g/dL) = 1; Systolic Blood Pressure <120 mmHg = 1, Tachycardia (heart rate >100 bpm) = 1. The model had a sensitivity of 83% and specificity of 53%. This simple, robust clinical tool can help individualize thromboprophylaxis for COVID-19 patients based on their VTE risk category.

SARS-COV-ATE risk assessment model for arterial thromboembolism in COVID-19.

Patients with SARS-CoV-2 infection are at an increased risk of cardiovascular and thrombotic complications conferring an extremely poor prognosis. COVID-19 infection is known to be an independent risk factor for acute ischemic stroke and myocardial infarction (MI). We developed a risk assessment model (RAM) to stratify hospitalized COVID-19 patients for arterial thromboembolism (ATE). This multicenter, retrospective study included adult COVID-19 patients admitted between 3/1/2020 and 9/5/2021. Among 3531 patients from the training cohort, 15.5% developed acute in-hospital ATE, including stroke, MI, and other ATE, compared to 13.4% in the validation cohort. The 16-item final score was named SARS-COV-ATE (Sex: male = 1, Age [40-59 = 2, > 60 = 4], Race: non-African American = 1, Smoking = 1 and Systolic blood pressure elevation = 1, Creatinine elevation = 1; Over the range: leukocytes/lactate dehydrogenase/interleukin-6, B-type natriuretic peptide = 1, Vascular disease (cardiovascular/cerebrovascular = 1), Aspartate aminotransferase = 1, Troponin-I [> 0.04 ng/mL = 1, troponin-I > 0.09 ng/mL = 3], Electrolytes derangement [magnesium/potassium = 1]). RAM had a good discrimination (training AUC 0.777, 0.756-0.797; validation AUC 0.766, 0.741-0.790). The validation cohort was stratified as low-risk (score 0-8), intermediate-risk (score 9-13), and high-risk groups (score ≥ 14), with the incidence of ATE 2.4%, 12.8%, and 33.8%, respectively. Our novel prediction model based on 16 standardized, commonly available parameters showed good performance in identifying COVID-19 patients at risk for ATE on admission.

Evidence showing lipotoxicity worsens outcomes in covid-19 patients and insights about the underlying mechanisms.

We compared three hospitalized patient cohorts and conducted mechanistic studies to determine if lipotoxicity worsens COVID-19. Cohort-1 (n = 30) compared COVID-19 patients dismissed home to those requiring intensive-care unit (ICU) transfer. Cohort-2 (n = 116) compared critically ill ICU patients with and without COVID-19. Cohort-3 (n = 3969) studied hypoalbuminemia and hypocalcemia's impact on COVID-19 mortality. Patients requiring ICU transfer had higher serum albumin unbound linoleic acid (LA). Unbound fatty acids and LA were elevated in ICU transfers, COVID-19 ICU patients and ICU non-survivors. COVID-19 ICU patients (cohort-2) had greater serum lipase, damage-associated molecular patterns (DAMPs), cytokines, hypocalcemia, hypoalbuminemia, organ failure and thrombotic events. Hypocalcemia and hypoalbuminemia independently associated with COVID-19 mortality in cohort-3. Experimentally, LA reacted with albumin, calcium and induced hypocalcemia, hypoalbuminemia in mice. Endothelial cells took up unbound LA, which depolarized their mitochondria. In mice, unbound LA increased DAMPs, cytokines, causing endothelial injury, organ failure and thrombosis. Therefore, excessive unbound LA in the circulation may worsen COVID-19 outcomes.

Update on Diagnosis and Treatment of Adult Pulmonary Alveolar Proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary surfactant homeostasis disorder resulting in buildup of lipo-proteinaceous material within the alveoli. PAP is classified as primary (autoimmune and hereditary), secondary, congenital and unclassifiable type based on the underlying pathogenesis. PAP has an insidious onset and can, in some cases, progress to severe respiratory failure. Diagnosis is often secured with bronchoalveolar lavage in the setting of classic imaging findings. Recent insights into genetic alterations and autoimmune mechanisms have provided newer diagnostics and treatment options. In this review, we discuss the etiopathogenesis, diagnosis and treatment options available and emerging for PAP.

Updates on community acquired pneumonia management in the ICU.

While the world is grappling with the consequences of a global pandemic related to SARS-CoV-2 causing severe pneumonia, available evidence points to bacterial infection with Streptococcus pneumoniae as the most common cause of severe community acquired pneumonia (SCAP). Rapid diagnostics and molecular testing have improved the identification of co-existent pathogens. However, mortality in patients admitted to ICU remains staggeringly high. The American Thoracic Society and Infectious Diseases Society of America have updated CAP guidelines to help streamline disease management. The common theme is use of timely, appropriate and adequate antibiotic coverage to decrease mortality and avoid drug resistance. Novel antibiotics have been studied for CAP and extend the choice of therapy, particularly for those who are intolerant of, or not responding to standard treatment, including those who harbor drug resistant pathogens. In this review, we focus on the risk factors, microbiology, site of care decisions and treatment of patients with SCAP.

Performance of Automated Telemetry in Diagnosing QT Prolongation in Critically Ill Patients.

BACKGROUND: QT prolongation increases the risk of ventricular arrhythmia and is common among critically ill patients. The gold standard for QT measurement is electrocardiography. Automated measurement of corrected QT (QTc) by cardiac telemetry has been developed, but this method has not been compared with electrocardiography in critically ill patients. OBJECTIVE: To compare the diagnostic performance of QTc values obtained with cardiac telemetry versus electrocardiography. METHODS: This prospective observational study included patients admitted to intensive care who had an electrocardiogram ordered simultaneously with cardiac telemetry. Demographic data and QTc determined by electrocardiography and telemetry were recorded. Bland-Altman analysis was done, and correlation coefficient and receiver operating characteristic (ROC) coefficient were calculated. RESULTS: Fifty-one data points were obtained from 43 patients (65% men). Bland-Altman analysis revealed poor agreement between telemetry and electrocardiography and evidence of fixed and proportional bias. Area under the ROC curve for QTc determined by telemetry was 0.9 (P < .001) for a definition of prolonged QT as QTc ≥ 450 milliseconds in electrocardiography (sensitivity, 88.89%; specificity, 83.33%; cutoff of 464 milliseconds used). Correlation between the 2 methods was only moderate (r = 0.6, P < .001). CONCLUSIONS: QTc determination by telemetry has poor agreement and moderate correlation with electrocardiography. However, telemetry has an acceptable area under the curve in ROC analysis with tolerable sensitivity and specificity depending on the cutoff used to define prolonged QT. Cardiac telemetry should be used with caution in critically ill patients.