critical care research and practice

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Explore the latest in critical care medicine, including management of respiratory failure, sepsis, HAI prevention, end-of-life care, and more.

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This Medical News story discusses the rise in ransomware cyberattacks on health care, as well as new cybersecurity initiatives.

This cohort study evaluates patient and event characteristics associated with cardiopulmonary resuscitation (CPR) duration among pediatric patients with in-hospital cardiac arrest without return of circulation and whether hospitals with longer median durations of CPR have higher survival rates among all children requiring CPR.

This cohort study investigates the association of neonatal sepsis episodes with retinopathy of prematurity, including treatment-warranted cases, among very preterm infants in Germany and Norway.

This systematic review and meta-analysis assesses the associations of sepsis alert systems in emergency departments with mortality and adherence to sepsis management guidelines.

This essay describes the author’s experience with delivering life-and-death information to patients and families in the intensive care unit.

This Viewpoint discusses the use of neuroimaging to tailor music-based protocols among infants in the neonatal intensive care unit (NICU).

• Hospital-Onset Bacteremia—Counting Them All JAMA Pediatrics Opinion July 15, 2024 Sepsis Resuscitation Infectious Diseases Neonatology Pediatrics Full Text | pdf link PDF

This mixed-methods study of clinical trials conducted during the COVID-19 pandemic surveys principal investigators and project coordinators and summarizes challenges, opportunities, and suggestions for running trials in a pandemic setting.

This systematic review and meta-analysis examines the use of termination of resuscitation rules to estimate patient survival of out-of-hospital cardiac arrest.

• Optimizing the Value of β-Lactam Antibiotics Through Extended Infusion JAMA Network Open Opinion July 2, 2024 Emergency Medicine Infectious Diseases Sepsis Resuscitation Pharmacy and Clinical Pharmacology Full Text | pdf link PDF open access

This cohort study assesses whether extended-infusion β-lactam therapy is associated with survival, adverse events, and/or emergence of resistance in adults with gram-negative bloodstream infections.

This cohort study assesses factors associated with family surrogates in Taiwan and their critically ill loved one’s categorization into 1 of 4 response classes based on the Quality of Dying and Death Questionnaire.

This cross-sectional study of US adults hospitalized with suspected community-onset sepsis examines trends in empirical broad-spectrum antibiotic use from 2017 to 2021.

This cohort study assesses whether various types of antibiotics and the length of exposure are associated with the incidence of bronchopulmonary dysplasia (BPD) among very preterm infants at low risk of early-onset sepsis (EOS) in China.

This cohort study examines data for infants in a sample of NICUs across the US to estimate the incidence rates and attributable mortality of hospital-onset bacteremia as well as determine associated clinical characteristics.

This Medical News article discusses a new Boston Medical Center initiative that helps patients with financial hardship pay their utility bills.

This cohort study evaluates whether intravenous opioids administered during mechanical ventilation are associated with opioid use following hospital discharge among medical (nonsurgical) patients.

This randomized clinical trial assessed whether adding dapagliflozin to standard care for patients with acute organ dysfunction could reduce the composite outcome of hospital mortality, initiation of kidney replacement therapy, and length of stay compared with standard care alone.

• Sodium-Glucose Cotransporter 2 Therapy for Acute Organ Dysfunction in Critically Ill Patients JAMA Opinion June 14, 2024 Full Text | pdf link PDF

This cross-sectional study compares differences in demographics, respiratory support modes, and clinical outcomes for children with respiratory syncytial virus before vs after the COVID-19 pandemic.

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Published by Wiley

Online ISSN: 2090-1313

Print ISSN: 2090-1305

Disciplines: Medicine, general & internal medicine, intensive/critical care

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Aims and scope

Critical Care Research and Practice is an open access journal publishing articles related to anesthesiology, perioperative and critical care medicine, and the integration of intraoperative management in preparation for postoperative critical care management. As part of Wiley’s Forward Series, this journal offers a streamlined, faster publication experience with a strong emphasis on integrity. Authors receive practical support to maximize the reach and discoverability of their work.

Recent articles

Background . This study aimed to investigate the demographic, clinical, and laboratory characteristics of sepsis patients who were admitted to our center during 2014–2020 and to employ cluster analysis, which is a type of machine learning, to identify distinct types of sepsis in Thai population. Methods . Demographic, clinical, laboratory, medicine, and source of infection data of patients admitted to medical wards of Siriraj Hospital (Bangkok, Thailand) during 2014–2020 were collected. Sepsis was diagnosed according to the Sepsis‐3 criteria. Nineteen demographic, clinical, and laboratory variables were analyzed using hierarchical clustering to identify sepsis subtypes. Results . Of 98,359 admissions, 18,030 (18.3%) had sepsis. Respiratory tract was the most common site of infection. The mean Sequential Organ Failure Assessment (SOFA) score was 4.21 ± 2.24, and the median serum lactate level was 2.7 mmol/L [range: 0.4–27.5]. Twenty percent of admissions required vasopressor. In‐hospital mortality was 19.6%. Ten sepsis subtypes were identified using hierarchical clustering. Three clusters (clusters L1–L3) were considered low risk, and seven clusters (clusters H1–H7) were considered high risk for in‐hospital mortality. Cluster H1 had prominent hematologic abnormalities. Clusters H3 and H5 had younger ages and significant hepatic dysfunction. Cluster H5 had multiple organ dysfunctions, and a higher proportion of cluster H5 patients required vasopressor, mechanical ventilation, and renal replacement therapy. Cluster H6 had more respiratory tract infection and acute respiratory failure and a lower SpO 2 /FiO 2 value. Conclusions . Cluster analysis revealed 10 distinct subtypes of sepsis in Thai population. Furthermore, the study is needed to investigate the value of these sepsis subtypes in clinical practice.

Background. Elevated red blood cell distribution width (RDW) levels are strongly associated with an increased risk of mortality in patients with congestive heart failure (CHF). Additionally, heart failure has been closely linked to diabetes. Nevertheless, the relationship between RDW and in-hospital mortality in the intensive care unit (ICU) among patients with both congestive heart failure (CHF) and diabetes mellitus (DM) remains uncertain. Methods. This retrospective study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, a comprehensive critical care repository. RDW was assessed as both continuous and categorical variables. The primary outcome of the study was in-hospital mortality at the time of hospital discharge. We examined the association between RDW on ICU admission and in-hospital mortality using multivariable logistic regression models, restricted cubic spline analysis, and subgroup analysis. Results. The cohort consisted of 7,063 patients with both DM and CHF (3,135 females and 3,928 males). After adjusting for potential confounders, we found an association between a 9% increase in mortality rate and a 1 g/L increase in RDW level (OR = 1.09; 95% CI, 1.05∼1.13), which was associated with 11 and 58% increases in mortality rates in Q2 (OR = 1.11, 95% CI: 0.87∼1.43) and Q3 (OR = 1.58, 95% CI: 1.22∼2.04), respectively, compared with that in Q1. Moreover, we observed a significant linear association between RDW and in-hospital mortality, along with strong stratified analyses to support the findings. Conclusions. Our findings establish a positive association between RDW and in-hospital mortality in patients with DM and CHF.

• Full-text available

Objective. Describe continuous infusion (CI) ketamine practices in pediatric intensive care units (PICUs) and evaluate its effect on pain/sedation scores, exposure to analgesics/sedatives, and adverse effects (AEs). Methods. Multicenter, retrospective, observational study in children <18 years who received CI ketamine between 2014 and 2017. Time spent in goal pain/sedation score range and daily cumulative doses of analgesics/sedatives were compared from the 24 hours (H) prior to CI ketamine to the first 24H and 25−48H of the CI. Adverse effects were collected over the first 7 days of CI ketamine. Results. Twenty-four patients from 4 PICUs were included; median (IQR) age 7 (1-13.25) years, 54% female (n = 13), 92% intubated (n = 22), 25% on CI vasopressors (n = 6), and 33% on CI paralytics (n = 8). Ketamine indications were analgesia/sedation (n = 21, 87.5%) and status epilepticus (n = 3, 12.5%). Median starting dose was 0.5 (0.48–0.70) mg/kg/hr and continued for a median of 2.4 (1.3–4.4) days. There was a significant difference in mean proportion of time spent within goal pain score range (24H prior: 74% ± 14%, 0–24H: 85% ± 10%, and 25−48H: 72% ± 20%; p=0.014). A significant reduction in median morphine milligram equivalents (MME) was seen (24H prior: 58 (8–195) mg vs. 0–24H: 4 (0–69) mg and p=0.01), but this was not sustained (25−48H: 24 (2–246) mg and p=0.29). Common AEs were tachycardia (63%), hypotension (54%), secretions/suctioning (29%), and emergence reactions (13%). Conclusions. Ketamine CI improved time in goal pain score range and significantly reduced MME, but this was not sustained. Larger prospective studies are needed in the pediatric population.

Introduction. Critically ill COVID-19 patients hospitalized in intensive care units (ICU) are immunosuppressed due to SARSCoV-2-related immunological effects and are administered immunomodulatory drugs. This study aimed to determine whether these patients carry an increased risk of multi-drug resistant (MDR) and especially carbapenem-resistant Gram-negative (CRGN) bacterial infections compared to other critically ill patients without COVID-19. Materials and Methods. A prospective case-control study was conducted between January 2022 and August 2023. The ICU patients were divided into two groups (COVID-19 and non-COVID-19). Differences in the incidence of CRGN infections from Klebsiella pneumoniae, Acinetobacter spp., and Pseudomonas aeruginosa were investigated. In addition, an indicator of the infection rate of the patients during their ICU stay was calculated. Factors independently related to mortality risk were studied. Results. Forty-two COVID-19 and 36 non-COVID-19 patients were analyzed. There was no statistically significant difference in the incidence of CRGN between COVID-19 and non-COVID-19 patients. The infection rate was similar in the two groups. Regarding the aetiological agents of CRGN infections, Pseudomonas aeruginosa was significantly more common in non-COVID-19 patients (p=0.007). COVID-19 patients had longer hospitalisation before ICU admission (p=0.003) and shorter ICU length of stay (LOS) (p=0.005). ICU COVID-19 patients had significantly higher mortality (p<0.001) and sequential organ failure assessment (SOFA) score (p<0.001) compared to non-COVID-19 patients. Μortality secondary to CRGN infections was also higher in COVID-19 patients compared to non-COVID-19 patients (p=0.033). Male gender, age, ICU LOS, and hospital LOS before ICU admission were independent risk factors for developing CRGN infections. Independent risk factors for patients’ mortality were COVID-19 infection, obesity, SOFA score, total number of comorbidities, WBC count, and CRP, but not infection from CRGN pathogens. Conclusions. The incidence of CRGN infections in critically ill COVID-19 patients is not different from that of non-COVID-19 ICU patients. The higher mortality of COVID-19 patients in the ICU is associated with higher disease severity scores, a higher incidence of obesity, and multiple underlying comorbidities, but not with CRGN infections.

Introduction. The advent of ceftazidime-avibactam (CAZ-AVI)-resistant carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates has been steadily documented in recent years. We aimed to identify risk factors of CAZ-AVI-resistant CRKP infection and assess clinical outcomes of patients. Methods. The study retrospectively examined the clinical and microbiological data of patients with ceftazidime avibactam susceptible and ceftazidime avibactam-resistant Klebsiella pneumonia carbapenem-resistant enterobacteriaceae infection to identify risk factors, clinical features, and outcomes using multivariate logistic regression analysis. Results. A total of 152 patients with CRKP infection were enrolled in this study. Patients with CAZ-AVI-resistant CRKP isolates (20/34 = 58.8%) had prior exposure to carbapenems (p=0.003) and had more tracheostomies (16/34 = 47.1%) (p=0.001). Only 8/28 (28.6%) patients with CAZ-AVI susceptible CRKP isolates died amongst those administered ceftazidime-avibactam compared to 49/90 (54.4%) who did not receive the same (p=0.016). 1/9 (11.1%) patients with CAZ-AVI-resistant CRKP isolates who received colistin died compared to 13/25 (52%) who did not receive colistin (p=0.03). There was no association between presence of CAZ-AVI-resistant CRKP isolates and overall mortality (odds ratio: 0.7; 95% CI: 0.3, 1.6), and no independent predictors of risk factors to overall mortality in the group with CAZ-AVI-resistant CRKP isolates were noted. Conclusion. Early advent of CAZ-AVI resistance in CRE isolates highlights the dynamic necessity of routine CAZ-AVI resistance laboratory testing and antimicrobial stewardship programmes focusing on the utilization of all antibiotics. Consolidating the hospital infection control of tracheostomies may help to prevent CAZ resistance in CRKP. Colistin may aid in decreasing of mortality rates among patients with CAZ-AVI CRKP isolates.

• Literature Review

Present day Jehovah’s Witness (JW) religion accounts for 8.5 million followers. A tenant feature of the JW faith is religious objection to transfusions of blood and blood products. Interpatient variability, as it pertains to blood and blood products may occur; hence, a confidential interview will determine which products individual may consent to (Marsh and Bevan, 2002). This belief and practice place great restrictions on treating medical professionals in scenarios of life-threatening anaemia and active haemorrhage. The review to follow explores the physiological and pathophysiological consequences of severe anaemia. Non-blood transfusion practices are explored, many of which are potentially lifesaving. Particular attention is drawn to the evolving science involving artificial oxygen carriers and their use in emergency situations. A greater safety profile ensures its future use amongst religious objectors to be greatly beneficial. Intravenous iron supplementation has enjoyed a lively debate within the critical care community. A review of recent systematic and meta-analysis supports its use in the ICU; however, more investigation is needed into the complementary use of hepcidin.

Introduction Gender variation in critically ill adults after resuscitation is reported in many studies. However, this variation is not well established when evaluating the physiological instability in this population. This study aimed to prospectively evaluate the gender variation in serious outcomes by the difficult airway physiological score (DAPS) among critically ill patients requiring endotracheal intubation (ETI). Methods This is a cohort study conducted from August 2021 to December 2022 in the emergency department of Aga Khan University. The prospective validity of the difficult airway physiological score was derived using retrospective data and includes 12 variables: sex, age, time of intubation, hypotension, respiratory distress, vomiting, shock index >0.9, pH < 7.3, fever, anticipated decline, Glasgow Coma Scale (GCS) < 15, and agitation. The serious outcomes were cardiac arrest, mortality (within 1 hour after intubation in emergency), hypotension (systolic blood pressure <90 mmHg), and oxygen desaturation (SpO2 < 92%). The difference between males and females was assessed using the chi-square test, and the association of gender and serious outcomes was explored using Cox and logistic regression analysis. ROC curve analysis and area under the curve assessed score validity separately in males and females with serious outcomes. Results We enrolled 326 patients with a mean age of 50.3 (±17.8), with 123 (33.7%) females and 203 (62.2%) males. 198 (60.7%) patients were >45 years old, of which 136 (67%) were male and 62 (50.4%) female. Cardiac arrest was observed in 56 (17.2%), with 24 (19.5%) females and 32 (15.8%) males, p value 0.348. Hypotension after intubation was observed in 132 (40.5%) patients, 56 (45.5%) females and 76 (37.4%) males, p value 0.149. Oxygen saturation (<92%) was observed in 80 (24.5%) patients, 32 (26%) females and 48 (23.6%) males, p value 0.630. In females, the DAPS of 11 had an area under the curve of 0.863 (0.74–0.91). The sensitivity of the score was 84.8%, the specificity was 71.9%, the PPV was 77.8%, and the NPV was 80.4% with an accuracy of 78.9%. In males, the DAPS score of 14 had an area under the curve of 0.892 (0.57–0.75). The sensitivity of the score was 67%, the specificity 93.8%, the PPV 92.2%, and the NPV 72.2% with an accuracy of 79.8%. Conclusions The Difficult Airway Physiological Score (DAPS) predicts the risk of serious outcomes after intubation with high precision and reliability with different score cutoffs between the two sexes, highlighting the gender variation of a difficult airway.

Delirium is a serious and complex problem facing critically ill patients. This retrospective study aimed to explore the association between prognostic nutrition index (PNI) and delirium in critically ill patients in the intensive care unit (ICU). This study was based on the Medical Information Mart Intensive Care IV (MIMIC IV) database. Patients over 18 years of age were enrolled. Univariate and multivariate logistic regression analyses were performed to explore the association between PNI and delirium. Tendency analysis, subgroups analysis, and restricted cubic spline (RCS) were selected to further certify the association. The receiver operating characteristic curve (ROC) was adopted to assess the predictability of PNI to delirium. Propensity score matching (PSM) was used to reduce the interference of confounders. A total of 3,105 patients participated in this study. As the grade of malnutrition increases, the incidence of delirium increases in all models. The odds ratios (OR) of delirium in the fully adjusted model were 1.00 (reference), 1.04 (0.80, 1.36), 1.53 (1.17, 1.99), and 1.93 (1.44, 2.59). Strong U-shaped curves were found with RCS analysis between delirium and PNI in the subgroups of patients over 60 years of age and patients with chronic obstructive pulmonary disease (COPD). After PSM, the ORs of delirium were 1.44 (1.16, 1.79) and 1.53 (1.22, 1.93), respectively, in the univariate and multivariate logistic regression models. PNI is negatively associated with the prevalence of delirium in critically ill adults in the ICU. PNI is an independent risk factor for the incidence of delirium in adults in the ICU.

Background Widespread drug shortages led to higher utilization of ketamine in our intensive care unit, especially among patients with SARS-CoV-2. Objectives To evaluate the impact of continuous infusion of ketamine on vasopressor requirements in patients with SARS-CoV-2. Method This was a single-center, retrospective, cohort study comparing mechanically ventilated (MV), adult patients with SARS-CoV-2 receiving either propofol or ketamine for at least 72 hours. Results 84 patients (mean age of 61-year-old, 68% male) were analyzed. 31 patients received ketamine, and 53 patients received propofol. Mean vasopressor doses were not significantly different between ketamine and propofol groups at prespecified timepoints. However, mean arterial pressures (MAP) were higher in the ketamine group at 24 h, 48 h, and 96 h postsedative initiation. The median opioid infusion requirements were 3 vs. 12.5 mg/hr (p < 0.0001) for ketamine and propofol groups, respectively. Comparing to propofol, C-reactive protein (CRP) values were significantly lower in the ketamine group at 24 h (7.53 vs. 15.9 mg/dL, p=0.03), 48 h (5.23 vs. 14.1 mg/dL, p=0.0083), and 72 h (6.4 vs. 12.1 mg/dL, p=0.0085). Conclusion In patients with SARS-CoV-2 on MV, there was no difference in the vasopressor requirement in patients receiving ketamine compared to propofol. Nevertheless, the use of ketamine was associated with higher MAP, reductions in CRP in select timepoints, and overall lower opioid requirements.

Introduction The objective of this study was to describe Do-Not-Resuscitate (DNR) practices in a tertiary-care intensive care unit (ICU) in Saudi Arabia, and determine the predictors and outcomes of patients who had DNR orders. Methods This retrospective cohort study was based on a prospectively collected database for a medical-surgicalIntensive CareDepartment in a tertiary-care center in Riyadh, Saudi Arabia (1999–2017). We compared patients who had DNR orders during the ICU stay with those with “full code.” The primary outcome was hospital mortality. The secondary outcomes included ICU mortality, tracheostomy, duration of mechanical ventilation, and length of stay in the ICU and hospital. Results Among 24790 patients admitted to the ICU over the 19-year study period, 3217 (13%) had DNR orders during the ICU stay. Compared to patients with “full code,” patients with DNR orders were older (median 67 years [Q1, Q3: 55, 76] versus 57 years [Q1, Q3: 33, 71], p < 0.0001), were more likely to be females (43% versus 38%, p < 0.0001), had worse premorbid functional status (WHO performance status scores 4-5: 606[18.9%] versus 1894[8.8%], p < 0.0001), higher prevalence of comorbid conditions, and higher APACHE II score (median 28 [Q1, Q3: 23, 34] versus 19 [Q1, Q3: 13, 25], p < 0.0001) and were more likely to be mechanically ventilated (83% versus 55%, p < 0.0001). Patients had DNR orders were more likely to die in the ICU (67.8% versus 8.5%, p < 0.0001) and hospital (82.4% versus 18.1%, p < 0.0001). On multivariable logistic regression analysis, the following were associated with an increased likelihood of DNR status: increasing age (odds ratio (OR) 1.01, 95% confidence interval (CI) 1.01–1.02), higher APACHE II score (OR 1.09, 95% CI 1.08–1.10), and worse WHO performance status score. Patients admitted in recent years (2012–2017 versus 2002–2005) were less likely to have DNR orders (OR 0.35, 95% CI 0.32–0.39, p < 0.0001). Patients with DNR orders had higher ICU mortality, more tracheostomies, longer duration of mechanical ventilation and length of ICU stay compared to patients with with “full code” but they had shorter length of hospital stay. Conclusion In a tertiary-care hospital in Saudi Arabia, 13% of critically ill patients had DNR orders during ICU stay. This study identified several predictors of DNR orders, including the severity of illness and poor premorbid functional status.

Background Kidney transplant recipients (KTRs) are a vulnerable immunocompromised population at risk of severe COVID-19 disease and mortality after SARS-CoV-2 infection. We sought to characterize the post-infection sequelae in KTRs at our center. Methods We studied all adult KTRs (with a functioning allograft) who had their first episode of SARS-CoV-2 infection between 04/2020 and 04/2022. Outcomes of interest included risk factors for hospitalization, all-cause mortality, COVID-19-related mortality, and allograft failure. Results Of 979 KTRs with SARS-CoV-2 infection, 381 (39%) were hospitalized. In the multivariate analysis, risk factors for hospitalization included advanced age/year (HR: 1.03, 95% CI: 1.02–1.04), male sex (HR: 1.29, 95% CI: 1.04–1.60), non-white race (HR: 1.48, 95% CI: 1.17–1.88), and diabetes as a cause of ESKD (HR: 1.77, 95% CI: 1.41–2.21). SARS-CoV-2 Vaccination was associated with decreased risk of hospitalization (HR: 0.73, 95% CI: 0.59–0.90), all-cause mortality (HR: 0.52, 95% CI: 0.37–0.74), and COVID-19-related mortality (HR: 0.47, 95% CI: 0.31–0.71) in the univariate and multivariate analyses. Risk factors for both all-cause and COVID-19-related mortality in the multivariate analyses included advanced age, hospitalization, and respiratory symptoms for hospital admission. Furthermore, additional risk factors for all-cause mortality in the multivariate analysis included being a non-white recipient and diabetes as a cause of ESKD, with being a recipient of a living donor as protective. Conclusions Hospitalization due to COVID-19-associated symptoms is associated with increased mortality. Vaccination is a protective factor against hospitalization and mortality.

Background A noninvasive and accurate method of identifying fluid responsiveness in hemodynamically unstable patients has long been sought by physicians. Carotid ultrasound (US) is one such modality previously canvassed for this purpose. The aim of this novel systematic review and meta-analysis is to investigate whether critically unwell patients who are requiring intravenous (IV) fluid resuscitation (fluid responders) can be identified accurately with carotid US. Methods The protocol was registered with PROSPERO on the 30/11/2022 (ID number: CRD42022380284). Studies investigating carotid ultrasound accuracy in assessing fluid responsiveness in hemodynamically unstable patients were included. Studies were identified through searches of six databases, all run on 4 November 2022, Medline, Embase, Emcare, APA PsycInfo, CINAHL, and Cochrane Library. Risk of bias was assessed using the QUADAS-2 and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines. Results were pooled, meta-analysis was conducted where amenable, and hierarchical summary receiver operating characteristic models were established to compare carotid ultrasound measures. Results Seventeen studies were included (n = 842), with 1048 fluid challenges. 441 (42.1%) were fluid responsive. Four different carotid US measures were investigated, including change in carotid doppler peak velocity (∆CDPV), carotid blood flow (CBF), change in carotid artery velocity time integral (∆CAVTI), and carotid flow time (CFT). Pooled carotid US had a pooled sensitivity, specificity, and AUROC with 95% confidence intervals (CI) of 0.73 (0.66–0.78), 0.82 (0.72–0.90), and 0.81 (0.78–0.85), respectively. ∆CDPV had sensitivity, specificity, and AUROC with 95% CI of 0.72 (0.64–0.80), 0.87 (0.73–0.94), and 0.82 (0.78–0.85), respectively. CBF had sensitivity, specificity, and AUROC with 95% CI of 0.70 (0.56–0.80), 0.80 (0.50–0.94), and 0.77 (0.78–0.85), respectively. Risk of bias and assessment was undertaken using the QUADAS-2 and GRADE tools. The QUADAS-2 found that studies generally had an unclear or high risk of bias but with low applicability concerns. The GRADE assessment showed that ∆CDPV and CBF had low accuracy for sensitivity and specificity. Conclusion It appears that carotid US has a limited ability to predict fluid responsiveness in critically unwell patients. ∆CDPV demonstrates the greatest accuracy of all measures analyzed. Further high-quality studies using consistent study design would help confirm this.

Objectives To characterize the association between pulmonary embolism (PE) severity and bleeding risk with treatment approaches, outcomes, and complications. Methods Secondary analysis of an 11-hospital registry of adult ED patients treated by a PE response team (August 2016–November 2022). Predictors were PE severity and bleeding risk. The primary outcome was treatment approach: anticoagulation monotherapy vs. advanced intervention (categorized as “immediate” or “delayed” based on whether the intervention was received within 12 hours of PE diagnosis or not). Secondary outcomes were death, clinical deterioration, and major bleeding. Results Of the 1832 patients, 139 (7.6%), 977 (53.3%), and 9 (0.5%) were classified as high-risk, intermediate-high, intermediate-low, and low-risk severity, respectively. There were 94 deaths (5.1%) and 218 patients (11.9%) had one or more clinical deterioration events. Advanced interventions were administered to 86 (61.9%), 195 (27.6%), and 109 (11.2%) patients with high-risk, intermediate-high, and intermediate-low severity, respectively.Major bleeding occurred in 61/1440 (4.2%) on ACm versus 169/392 (7.6%) with advanced interventions (p <0.001): bleeding withcatheter-directed thrombolysiswas 19/145 (13.1%) versus 33/154(21.4%) with systemic thrombolysis,p= 0.07. High risk was twice as strong as intermediate-high risk for association with advanced intervention (OR: 5.3 (4.2 and 6.9) vs. 1.9 (1.6 and 2.2)). High risk (OR: 56.3 (32.0 and 99.2) and intermediate-high risk (OR: 2.6 (1.7 and 4.0)) were strong predictors of clinical deterioration. Major bleeding was significantly associated with advanced interventions (OR: 5.2 (3.5 and 7.8) for immediate, 3.3 (1.8 and 6.2)) for delayed, and high-risk PE severity (OR: 3.4 (1.9 and 5.8)). Conclusions Advanced intervention use was associated with high-acuity patients experiencing death, clinical deterioration, and major bleeding with a trend towards less bleeding with catheter-directed interventions versus systemic thrombolysis.

Objective Intensive care unit (ICU)-acquired weakness often occurs in patients with invasive mechanical ventilation (IMV). Early active mobility may reduce ICU-acquired weakness, improve functional status, and reduce disability. The aim of this study was to investigate whether high-intensity early mobility improves post-ICU discharge functional status of IMV patients. Methods 132 adult patients in the ICU who were undergoing IMV were randomly assigned into two groups with a ratio of 1 : 1, with one group received high-intensity early mobility (intervention group, IG), while the other group received conventional treatment (control group, CG). The functional status (Barthel Index (BI)), capacity of mobility (Perme score and ICU Mobility Scale (IMS)), muscle strength (Medical Research Council sum scores (MRC-SS)), mortality, complication, length of ICU stay, and duration of IMV were evaluated at ICU discharge or after 3-month of ICU discharge. Results The patient's functional status was improved (BI scores 90.6 ± 18.0 in IG vs. 77.7 ± 27.9 in CG; p=0.005), and capacity of mobility was increased (Perme score 17.6 ± 7.1 in IG vs. 12.2 ± 8.5 in CG, p < 0.001; IMS 4.7 ± 2.6 in IG vs. 3.0 ± 2.6 in CG, p < 0.001). The IG had a higher muscle strength and lower incidence of ICU-acquired weakness (ICUAW) than that in the CG. The incidence of mortality and delirium was also lower than CG at ICU discharge. However, there were no differences in terms of length of ICU stay, duration of IMV, ventilator-associated pneumonia, and venous thrombosis. Conclusions High-intensity early mobility improved the patient's functional status and increased capacity of mobility with IMV. The benefits to functional status remained after 3 month of ICU discharge. Other benefits included higher muscle strength, lower incidence of ICUAW, mortality, and delirium in IG.

February 2024

Background High-flow nasal cannula (HFNC) therapy is a common respiratory support in patients with COVID-19 pneumonia. Predictive tools for the evaluation of successful weaning from HFNC therapy for COVID-19 pneumonia have been limited. This study aimed to develop a new predictor for weaning success from HFNC treatment in patients with COVID-19 pneumonia. Methods We conducted a retrospective cohort study at Thammasat University Hospital, Thailand. Patients with COVID-19 pneumonia requiring HFNC therapy from April 2020 to September 2021 were included. The ROX index was defined as the ratio of oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) to respiratory rate. The CROX index was defined as the ratio of C-reactive protein (CRP) to the ROX index. dCROX was defined as the difference in CROX index between 24 hours and 72 hours. Weaning success was defined as the ability to sustain spontaneous breathing after separation from HFNC without any invasive or noninvasive ventilatory support for ≥48 hours or death. Results A total of 106 patients (49.1% male) were included. The mean age was 62.1 ± 16.2 years. Baseline SpO2/FiO2 was 276.1 ± 124.8. The rate of HFNC weaning success within 14 days was 61.3%. The best cutoff value of the dCROX index to predict HFNC weaning success was 3.15 with 66.2% sensitivity, 70.7% specificity, and an area under the ROC curve (AUC) of 0.71 (95% CI: 0.59–0.81, p < 0.001). The best cutoff value of the ROX index was 9.13, with 75.4% sensitivity, 78.0% specificity, and an AUC of 0.79 (95% CI: 0.69–0.88, p < 0.001). Conclusions ROX index has the highest accuracy for predicting successful weaning from HFNC in patients with COVID-19 pneumonia. dCROX index is the alternative tool for this setting. However, a larger prospective cohort study is needed to verify these indices for determining separation from HFNC therapy. This trial is registered with TCTR20221107004.

Background. The pulmonary artery pulsatility index (PAPi) has been shown to correlate with right ventricular (RV) failure in patients with cardiac disease. However, the association of PAPi with right ventricular function following cardiac surgery is not yet established. Methods. PAPi and other hemodynamic variables were obtained postoperatively for 959 adult patients undergoing cardiac surgery. The association of post-bypass right ventricular function and other clinical factors to PAPi was evaluated using linear regression. A propensity-score matched cohort for PAPi ≥ 2.00 was used to assess the association of PAPi with postoperative outcomes. Results. 156 patients (16.3%) had post-bypass right ventricular dysfunction defined by visualization on transesophageal echocardiography. There was no difference in postoperative PAPi based on right ventricular function (2.12 vs. 2.00, p = 0.21 ). In our matched cohort (n = 636), PAPi < 2.00 was associated with increased incidence of acute kidney injury (23.0% vs 13.2%, p < 0.01 ) and ventilator time (6.0 hours vs 5.6 hours, p = 0.04 ) but not with 30-day mortality or intensive care unit length of stay. Conclusion. In a general cohort of patients undergoing cardiac surgery, postoperative PAPi was not associated with postcardiopulmonary bypass right ventricular dysfunction. A postoperative PAPi < 2 may be associated with acute kidney injury.

January 2024

Background KL-6 is a biomarker of interstitial lung injury and increases during repair. Aim Our aim was to determine the predictive value of plasma KL-6 for the development of bronchopulmonary dysplasia (BPD) in preterm infants. Methods Ninety-five extremely preterm infants (EPIs), born at <28 gestational age (GA), were divided into two main BPD groups as follows: the moderate/severe and the no/mild group. KL-6 was analyzed on days 7 and 14. Binary logistic regression analyses and ROC curve analyses were performed. Results Infants <26 + 0 weeks' GA have higher mean KL-6 than infants >25 + 6 weeks' GA on 7 and 14 days (335 vs. 286 U/ml and 378 vs. 260 U/ml; p = 0.005 and 0.018, respectively). In the binary regression model at KL-6 day 7, three of the prognostic factors remained significant—mechanical ventilation OR: 10.38 (95% CI: 3.57–30.14), PDA OR: 6.39 (95% CI: 0.87–46.74), and KL-6 OR: 4.98 (95% CI: 1.54–16.08). The AUC was 0.86 with a sensitivity and specificity of 79% at a cutoff value ≥0.34. In the binary regression model at KL-6 day 14, six of the prognostic factors were significant—PDA OR: 23.34 (95% CI: 2.14–254.24), KL-6 OR: 13.59 (95% CI: 3.19–57.96), GA OR: 4.58 (95% CI: 1.16–18.06), mechanical ventilation OR: 4.45 (95% CI: 1.23–16.16), antenatal steroids OR: 0.19 (95% CI: 0.04–0.95), and gender (female OR: 0.30 (95% CI 0.08–1.12)). The AUC was 0.91, and the sensitivity and accuracy for a cutoff ≥0.37 were 89% and 85%, respectively. Conclusion KL-6 could be a useful screening biomarker for early detection of infants at increased risk for developing BPD.

December 2023

Objective To explore the clinical application of a new type of protective sputum suction device (PSSD) in patients with tracheotomy or tracheal intubation and to evaluate the protective effect of PSSD against cross-infection between medical staffs and patients. Methods A novel PSSD was designed which can assist closed sputum suction operation without disconnecting the ventilator. 32 patients with tracheotomy were included to study the protective effect and safety of this device. Patients' vital signs including heart rate, respiratory rate, mean arterial pressure, and blood oxygen saturation were recorded to compare the influence of open suction and closed suction (performed with this novel device). To verify the antisplash effect of this device on airway secretions, bacterial samples were collected from the hands of the suction operators and the environment near the endotracheal tube orifice before and after the two suction processes. In addition, the satisfaction of the two suction methods was compared through the questionnaire of suction staff. Finally, with the assistance of this device, an attempt was made to complete the bronchoscopy without weaning of ventilator. Results Compared with open sputum suction, closed sputum suction has a smaller decrease in patients' blood oxygen saturation (P < 0.05), and no significant differences in other vital signs. Compared with open sputum suction, bacteria from the hands of suction staffs and the surrounding environment of the endotracheal tube were barely detected in closed suction. A questionnaire survey of sputum suction nurses suggested that the satisfaction with use and protective effect of the closed suction were better than open suction. In addition, bronchoscopy can be successfully completed with the assistance of this device, which is not possible for other breathing tubes. Conclusion This closed sputum suction device has little effect on the oxygen saturation of patients but has excellent protective effects for medical staff against cross-infection. It has a unique advantage that can assist in completing the fiberoptic bronchoscopy with continuous ventilator-assisted breathing.

November 2023

Acute kidney injury (AKI) poses a significant challenge in critically ill patients. To determine the prevalence, risk factors, and mortality rate of AKI among nonsurgical critically ill patients in Jordan University Hospital, we conducted a retrospective study using a consecutive sampling method, including 457 nonsurgical critically ill patients admitted to the medical intensive care unit (MICU) from January to June 2021. The mean age was 63.8 ± 18 years, with 196 (42.8%) developing AKI during their stay in the MICU. Among AKI nonsurgical patients, pulmonary diseases (n = 52; 34.5%) emerged as the primary cause for admission, exhibiting the highest prevalence, followed by sepsis (n = 40; 20.4%). Furthermore, we found that older age (adjusted OR (AOR): 1.04; 95% confidence interval (CI): 1.04–1.06; p = 0.003 ), preadmission use of diuretics (AOR: 2.12; 95% CI: 1.06–4.25; p = 0.03 ), use of ventilators (2.19; 95% CI: 1.12–2.29; p = 0.02 ), and vasopressor use during MICU stay (AOR: 4.25; 95% CI: 2.1308.47; p = 0.001 ) were observed to have higher mortality rates. Prior utilization of statins before admission exhibited a significant association with reduced mortality rate (AOR: 0.42; 95% CI: 0.2–0.85; p = 0.02 ). Finally, AKI was associated with a higher mortality rate during MICU stay (AOR: 2.44; 95% CI: 1.07–5.56; p = 0.03 ). The prevalence of AKI among nonsurgical patients during MICU stay is higher than what has been reported previously in the literature, which highlights the nuanced importance of identifying more factors contributing to AKI in developing countries, and hence providing preventive measures and adhering to global strategies are recommended.

Introduction Proper oxygen therapy is crucial in hospitals, particularly intensive care units, to ensure safety and accuracy. The role of nurses during oxygen therapy is vital, as their knowledge and correct performance significantly impact patients' clinical conditions. A study was carried out to examine the knowledge and performance of nurses regarding safe oxygen therapy. The study aimed to identify the obstacles hindering safe oxygen therapy and assess the impact of training on the knowledge and performance of intensive care nurses. Methods This study was conducted among the ICU nurses at Shahid Rahnemoun Teaching Hospital in Yazd, Iran. The study method is a sequential combination of descriptive, qualitative, and educational phases. The first stage involved examining the knowledge and performance of 80 ICU nurses in oxygen therapy. The study employed content analysis to elaborate on participants' perspectives on safe oxygen therapy challenges and potential solutions. The third phase involved a two-group study with pre- and post-tests to examine the effect of training on ICU nurses' knowledge and performance in oxygen therapy. Results The study found that intervention and control groups had low average scores in knowledge, performance, and total score of oxygen therapy before the study, with no significant difference. There was a significant difference between intervention and control groups one and three months after the intervention in the areas of knowledge (after-1 month 24.41 vs. 20.29, 95% CI [3.144–5.098], after-3 month 22.13 vs. 20.24, 95% CI [0.729–3.053]), performance (after-1 month 21.54 vs. 18.05, 95% CI [2.898–4.073], after-3 month 19.74 vs. 18.63, 95% CI [0.400–1.824]), and total score of oxygen therapy (after-1 month 45.95 vs. 38.34, 95% CI [6.288–8.925], after-3 month 41.87 vs. 38.87, 95% CI [1.394–4.613]). Conclusion The study's findings revealed that nurses in ICUs lack the appropriate knowledge and performance in oxygen therapy. A lack of knowledge and correct practice, insufficient monitoring of oxygen therapy, and defects in hospital equipment are contributing factors. The training was found to improve the knowledge and performance of nurses significantly. Consistent training at shorter intervals is suggested for nurses to keep their knowledge current.

Background Nearly, 75% of patients post-CABG complain of moderate to severe pain during their hospital stay. Nonpharmacological interventions have been investigated; however, the effect of Holy Quran recital post-CABG is still not well studied, especially in developing Islamic countries. Objective To investigate the effect of listening to the Holy Quran recital on pain and length of stay post-CABG. Methods This was a randomized control trial on 132 patients recruited from four hospitals in Amman, Jordan. The intervention group listened to the Holy Quran recited for 10 minutes twice daily while the control group received the usual care. Data were analyzed using paired and independent samples t-tests. Results Paired t-test testing showed that there was a significant reduction in the pain level, (M [SD], 6.82 [2.27] vs. 4.65 [2.18], t = 23.65, p < 0.001) for the intervention group. In addition, the intervention group had shorter LoS in the ICU and in the hospital compared to the control group, (M [SD], 5.0 [4.02] vs. 6.58 [4.18], t = −2.1, p < 0.05), (M [SD], 10.15 [9.21] vs. 15.01 [13.14], t = −2.6, p < 0.05), respectively. Conclusions Listening to the Quran was significantly effective in improving pain intensity among post-CABG patients and shortening their hospital/ICU stay. This trial is registered with NCT05419554.

October 2023

Background The critical care resuscitation unit (CCRU) facilitates interhospital transfer (IHT) of critically ill patients for immediate interventions. Due to these patients' acuity, it is uncommon for patients to be directly discharged home from this unit, but it does happen on occasion. Since there is no literature regarding outcomes of patients being discharged from a resuscitation unit, our study investigated these patients' outcome at greater than 12 months after being discharged directly from the CCRU. Methods We performed a retrospective cohort study of all adult patients directly discharged from the CCRU between January 01, 2017, and December 31, 2020. The primary outcome was number of ED visits or hospitalizations within 6 months. Secondary outcomes were number of ED visits or hospitalizations within 6, 12, and >12 months from CCRU discharge. Results We analyzed 145 patients' records. Mean age was 56 (standard deviation [SD] ± 19), with a majority being male (72%) and Caucasian (58%). The most common discharge destination was home (139 patients, 96% of total subjects) versus hospice (2%) or nursing facilities (2%). Most patients (55%) did not have any hospital revisits within the first 6 months of discharge, while 31% had 1-2 revisits, and 14% had ≥3 revisits. The most common discharge diagnoses were soft tissue infection (16.5%), aortic dissection (14%), and stroke (11%). Factors which were associated with a greater likelihood of any return hospital visit within 6 months receiving mechanical ventilation during CCRU stay (coefficient −2.23, 95% CI 0.01–0.87, P=0.036), while high hemoglobin on CCRU discharge was associated with no ED revisit (coeff. 0.42, 95% CI 1.15–2.06, P=0.004). Conclusions Most patients who were discharged from the CCRU did not require any hospital revisits in the first 6 months. Requiring mechanical ventilation and having soft tissue infection were associated with high unplanned hospital revisits following discharge. Further research is needed to validate these findings.

Background: Successful execution of invasive procedures in acute care settings, including tracheal intubation, requires careful coordination of an interprofessional team. The stress inherent to the intensive care unit (ICU) environment may threaten the optimal communication and planning necessary for the safe execution of this complex procedure. The objective of this study is to characterize the perceptions of interprofessional team members surrounding tracheal intubations in the pediatric ICU (PICU). Methods: This is a single-center survey-based study of staff involved in the intubation of pediatric patients admitted to a tertiary level academic PICU. Physicians, nurses, and respiratory therapists (RT) involved in tracheal intubations were queried via standardized, discipline-specific electronic surveys regarding their involvement in procedural planning and overall awareness of and comfort with the intubation plan. Qualitative variables were assessed by both Likert scales and free-text comments that were grouped and analyzed thematically. Results: One hundred and eleven intubation encounters were included during the study time period, of which 93 (84%) had survey responses from at least 2 professional teams. Among those included in the analysis, the survey was completed 244 times by members of the PICU teams including 86 responses from physicians, 76 from nurses, and 82 from RTs. Survey response rates were >80% from each provider team. There were significant differences in interprofessional team comfort with nurses feeling less well informed and comfortable with the intubation plan and process compared to physicians and RTs (p < 0.001 for both). Qualitative themes including clear communication, adequate planning and preparation prior to procedure initiation, and clear definition of roles emerged among both affirmative and constructive comments. Conclusions: Exploration of provider perceptions and emergence of constructive themes expose opportunities for teamwork improvement strategies involving intubations in the PICU. The use of a preintubation checklist may improve organization and communication amongst team members, increase provider morale, decrease team stress levels, and, ultimately, may improve patient outcomes during this high stakes, coordinated event.

Introduction: Sepsis, the leading cause of death in hospitalized patients globally, was investigated in this study, examining the varying effects of positive fluid balance on sepsis subtypes through causal inference. Methods: In this study, data from the eICU database were utilized, extracting 35 features from sepsis patients. Fluid balance during ICU stay was the treatment, and ICU mortality was the primary outcome. Data preprocessing ensured linear assumptions for logistic regression. Binarized positive fluid balance with mortality was examined using DoWhy's logistic regression, while continuous data were analyzed with random forest T-learner. ATE served as the primary metric. Results: Results revealed that septic patients with higher fluid balance had worse mortality outcomes, with an ATE of 0.042 (95% CI: (0.034, 0.047)) using logistic regression and an ATE of 0.0340 (95% CI: (0.028-0.040)) using T-learner. In the pulmonary sepsis subtype, higher mortality was associated with increased fluid balance, showing an ATE of 0.047 (95% CI: (0.037, 0.055)) using logistic regression and an ATE of 0.28 (95% CI: (0.22, 0.34)) with T-learner. Conversely, urinary sepsis patients had improved mortality with higher fluid balance, presenting an ATE of -0.135 (95% CI: (-0.024, -0.0035)) using logistic regression and an ATE of -0.28 (95% CI: (-0.34, -0.22)) with T-learner. Conclusion: Our research implies that fluid balance impact on ICU mortality differs among sepsis subtypes. Positive fluid balance raises mortality in sepsis and pulmonary sepsis but may protect against urinary sepsis. Further trials are needed to confirm these findings.

September 2023

Background: Rapid shallow breathing index (RSBI) has been widely used as a predictor of extubation outcome in mechanically ventilated patients. We hypothesize that the rate of change of RSBI between the beginning and end of a 120-minute spontaneous breathing trial (SBT) could be a better predictor of extubation outcome than a single RSBI measured at the end of SBT in mechanically ventilated patients. Methodology. In this prospective observational study, we enrolled 193 patients who met the inclusion criteria, of whom 33 patients were unable to tolerate a 120-minute SBT and were excluded from the study. The study population consisted of 160 patients, categorized into three subgroups: patients with normal lung (no reported history of respiratory diseases), patients with airway disease, and patients with parenchymal disease who completed 120 minutes of SBT on low levels of pressure support ventilation. RSBI was obtained from the ventilator display at the 5th and the 120th minutes of SBT. The rate of change of RSBI (RSBI 5-120) was calculated as (RSBI 2-RSBI 1)/RSBI 1 × 100. Receiver-operating characteristic (ROC) curves were plotted for RSBI 5-120 and RSBI 120 in all patients and among the three subgroups (normal group, airway group, and parenchymal group) to compare the superiority of their best thresholds in predicting extubation failure. Results: The RSBI 5-120 threshold for extubation failure in the entire patient group was 23% with an overall accuracy of 88% (AUC = 0.933, sensitivity = 91%, and specificity = 86%) and the threshold of RSBI 120 for extubation failure in the entire patient group was 70 breaths/min/L with an overall accuracy of 82% (AUC = 0.899, sensitivity = 85%, and specificity = 81%). In patients in the normal lung group, the threshold of RSBI 5-120 was 22%, with an overall accuracy of 89% (AUC = 0.892, sensitivity = 87.5%, and specificity = 90%), and the RSBI 120 threshold was 70 breaths/min/L, with an overall accuracy of 89% (AUC = 0.956, sensitivity = 88%, and specificity = 90%). The RSBI 5-120 threshold in patients with airway disease was 25% with an accuracy of 86% (AUC = 0.892, sensitivity = 85%, and specificity = 86%) and the threshold of RSBI 120 was 73 breaths/min/L with an accuracy of 83% (AUC = 0.874, sensitivity = 85%, and specificity = 82%). In patients in the parenchymal disease group, the threshold of RSBI 5-120 was 24%, with an accuracy of 90% (AUC = 0.966, sensitivity = 92%, and specificity = 89%) and RSBI 120 threshold was 71 breaths/min/L, which was 88% accurate (AUC = 0.893, sensitivity = 85%, and specificity = 89%). Conclusion: The rate of change of RSBI between the 5th and 120th minutes was moderately more accurate than the single value of RSBI measured at the 120th minute in predicting extubation outcome.

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Division of Trauma Surgical Critical Care and Burns, United States

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School of Medicine, Indiana University, United States

Research Center for Evidence-Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran, Iran

OSF HealthCare, United States

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, United States

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Leverage the opportunities of data science and learn more about the annual SCCM Datathon and Discovery’s efforts into data standardization, harmonization, and sharing.

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Find a list of the current Endorsed Projects, Discovery Programs, and published works. Learn about the benefits of submitting a proposal to Discovery and having your proposal become an Endorsed project.

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Tuesday, august 20, 2024 - tuesday, august 20, 2024, ​the role of ai/ml in prediction modeling.

Review recent computing trends as they relate to research, education, and clinical practice in the intensive care unit.

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Discovery clinical investigators meeting.

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Recent Publications

Association of Active Renin Content With Mortality in Critically Ill Patients: A Post Hoc Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis Trial Busse LW, Schaich CL, Chappell MC, et al; Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) Investigators. Association of active renin content with mortality in critically ill patients: a post hoc analysis of the Vitamin C, Thiamine, and Steroids in Sepsis Trial. Crit Care Med . 2023 Nov 10. Online ahead of print. doi: 10.1097/CCM.0000000000006095. Program Type: VICTAS DISCOVERY

Biomarker-Concordant Steroid Administration in Severe Coronavirus Disease-2019 Tekin A, Domecq JP, Morales DJV, et al; Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group. J Intensive Care Med . 2023 Nov;38(11):1003-1014. doi: 10.1177/08850666231177200. Epub 2023 May 24.PMID: 37226483 Program Type: VIRUS DISCOVERY

Effects of Timing of Invasive Mechanical Ventilation in Patients With Shock. An Analysis of the Multicenter Prospective Observational VOLUME-CHASERS Cohort Goel NN, Chen JT, Roberts R, Sevransky J, Gong MN, Mathews KS; VOLUME-CHASERS Study Group; Society of Critical Care Medicine Discovery Network. Effects of timing of invasive mechanical ventilation in patients with shock. An analysis of the multicenter prospective observational VOLUME-CHASERS cohort. J Intensive Care Med . 2022 Nov;37(11):1435-1441. doi: 10.1177/08850666221081102. Program Type: VOLUME-CHASERS DISCOVERY

The Association of Early Systemic Corticosteroids and Secondary Infection Amongst Hospitalized COVID-19 Patients: Results from the SCCM Discovery Virus COVID-19 Registry Bansal VB, Jain NK, Lal A, Domecq JP, Tekin A, Mir M, Attallah JN, Hassan E, Ahmed H, Anwar M, Khedr A, Kumar V, Robinson S, Kondori MJ, Koritala T, Boman K, Cartin-Ceba R, Christie A, Armaignac D, La Nou A, Sanghavi D, Walkey AJ, Kashyap R, Khan SA. The Association of Early Systemic Corticosteroids and Secondary Infection Amongst Hospitalized COVID-19 Patients: Results from the SCCM Discovery Virus COVID-19 Registry. Abstract presented at CHEST 2023; October 8-11, 2023. CHEST . 2023;164(4):A1755-A1756. doi:10.1001/chest.2023.164.4_MeetingAbstracts.A1755-A1756 Program Type: VIRUS DISCOVERY

Impact of Early Tracheostomy on Hospitalization Outcomes in Mechanically Ventilated COVID-19 Patients Isha S, Khadka S, Shrestha R, Satashia P, Balasubramanian P, Jenkins A, Hanson A, Singh K, Jena A, Tekin A, Bansal V, Kashyap R, Balavenkataraman A, Khan SA, Diaz Milian R, Patel NM, Quinones Q, Kiley S, Bhattacharyya A, Shapiro AB, Chaudhary S, Guru PK, Moreno Franco P, Sanghavi D. Impact of Early Tracheostomy on Hospitalization Outcomes in Mechanically Ventilated COVID-19 Patients. Abstract presented at CHEST 2023; October 8-11, 2023. CHEST . 2023;164(4):A1755-A1756. doi:10.1001/chest.2023.164.4_MeetingAbstracts.A1755-A1756 Program Type: VIRUS DISCOVERY

Critical Care

Exciting News: Critical Care achieves 2023 Impact Factor of 8.8!

A message from the Jean-Louis Vincent, Editor-in-Chief

We are excited to share with you some excellent news just released by Clarivate Analytics ˗  after the anticipated decline in impact factors that followed the exceptional years of the COVID pandemic, the 2023 Impact Factor for Critical Care is 8.8! Read more...

CALL FOR PAPERS: THE FUTURE OF INTENSIVE CARE MEDICINE

This collection focus on all aspects related to the future of Intensive Care Medicine, including but not limited to: organization, staffing, monitoring systems, new therapies, future organ support systems, ethical aspects.

CALL FOR PAPERS: PERSONALIZED MEDICINE IN THE ICU

After so many negative randomized, controlled trials, that have evaluated a number of simplified therapeutic interventions that could be applied to large patient populations, people are turning their interest back to personalized medicine. This collection shares thoughts based on scientific data and help the clinician to individualize the different aspects of the patient management.

PROFESSIONALLY PRODUCED VISUAL ABSTRACTS FOR CRITICAL CARE

Critical Care  encourages authors to submit a visual abstract along with their manuscripts. As an author submitting to the journal, you may wish to make use of services provided at Springer Nature for high quality and affordable visual abstracts where you are entitled to a 20% discount. Click  here  to find out more about the service, and your discount will be automatically be applied when using this link.

Meeting Abstracts - 43rd International Symposium on Intensive Care and Emergency Medicine

Aims and scope, trending neuroscience topics in icu management.

In this collection, we have compiled several articles, each succinctly reviewing the latest information with respect to Septic-Encephalopathy, Critical Illness Weakness & Neuropathy, EEG Utility in the ICU, Ventilation Concerns & Therapeutics in TBI & Stroke, and a Clinical Algorithm for Neurological Multi-Modal Monitoring.

EDITOR'S PICK - THE EUROPEAN GUIDELINE ON MANAGEMENT OF MAJOR BLEEDING AND COAGULOPATHY FOLLOWING TRAUMA: SXITH EDITION

Severe trauma represents a major global public health burden and the management of post-traumatic bleeding continues to challenge healthcare systems around the world. Post-traumatic bleeding and associated traumatic coagulopathy remain leading causes of potentially preventable multiorgan failure and death if not diagnosed and managed in an appropriate and timely manner. This sixth edition of the European guideline on the management of major bleeding and coagulopathy following traumatic injury aims to advise clinicians who care for the bleeding trauma patient during the initial diagnostic and therapeutic phases of patient management.

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Artificial intelligence in acute medicine: a call to action

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Editorial | 06 August 2019 Is this patient really “(un)stable”? How to describe cardiovascular dynamics in critically ill patients Jean-Louis Vincent, Maurizio Cecconi and Bernd Saugel

Research | 01 August 2019 Vitamin A deficiency in critically ill children with sepsis Xuepeng Zhang, Kaiying Yang, Linwen Chen, Xuelian Liao, Liping Deng, Siyuan Chen and Yi Ji

Letter | 30 July 2019 Vitamin C administration in the critically ill: a summary of recent meta-analyses Anitra C. Carr

Research | 24 July 2019 Association of sublingual microcirculation parameters and endothelial glycocalyx dimensions in resuscitated sepsis​​​​​​​ Alexandros Rovas, Laura Mareen Seidel, Hans Vink, Timo Pohlkötter, Hermann Pavenstädt, Christian Ertmer, Michael Hessler and Philipp Kümpers

Editorial | 04 July 2019 How I manage intracranial hypertension​​​​​​​ Chiara Robba and Giuseppe Citerio

Body temperature correlates with mortality in COVID-19 patients

Authors: Serena Tharakan, Koichi Nomoto, Satoshi Miyashita and Kiyotake Ishikawa

The Letter to this article has been published in Critical Care 2020 24 :460

36th International Symposium on Intensive Care and Emergency Medicine

Authors: R. M. Bateman, M. D. Sharpe, J. E. Jagger, C. G. Ellis, J. Solé-Violán, M. López-Rodríguez, E. Herrera-Ramos, J. Ruíz-Hernández, L. Borderías, J. Horcajada, N. González-Quevedo, O. Rajas, M. Briones, F. Rodríguez de Castro, C. Rodríguez Gallego, F. Esen…

Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group

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Weaning from mechanical ventilation

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The Erratum to this article has been published in Critical Care 2006 10 :414

The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition

Authors: Donat R. Spahn, Bertil Bouillon, Vladimir Cerny, Jacques Duranteau, Daniela Filipescu, Beverley J. Hunt, Radko Komadina, Marc Maegele, Giuseppe Nardi, Louis Riddez, Charles-Marc Samama, Jean-Louis Vincent and Rolf Rossaint

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The psychological impact of intensive care

06 December 2018

The gender gap in critical care medicine: how are we doing globally?

04 October 2018

Big data, big ethics: how to handle research data from medical emergency settings?

13 September 2018

Prof Jean-Louis Vincent, Editor-in-Chief

Prof. Vincent, MD, PhD, is a Professor of Intensive Care at the University of Brussels and an intensivist in the Department of Intensive Care at Erasme University Hospital in Brussels. He has served as the Past-President of the World Federation of Societies of Intensive and Critical Care Medicine (WFSICCM), the Belgian Society of Intensive Care Medicine (SIZ), the European Society of Intensive Care Medicine (ESICM), and the European Shock Society (ESS). Additionally, he was the Past-Chair of the International Sepsis Forum (ISF) and is a member of the Royal Medical Academy of Belgium. With a prolific publication record, Prof. Vincent has authored over 1300 journal articles and holds an h-index of 151 (Source: Web of Science).

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Annual Journal Metrics

Citation Impact 2023 Journal Impact Factor: 8.8 5-year Journal Impact Factor: 10.4 Source Normalized Impact per Paper (SNIP): 2.508 SCImago Journal Rank (SJR): 2.975

Speed 2023 Submission to first editorial decision (median days): 4 Submission to acceptance (median days): 51

Usage 2023 Downloads: 8,478,308 Altmetric mentions: 31,789

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ISSN: 1364-8535

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Fellows Research

• Manuscripts
• Books / Book Chapters
• Case Reports
• Vazquez R, Vasquez Guillamet C, Rishi M, Florindez J, Dhawan P, Allen A, Manthous C, Lighthall G. Physical Examination in the Intensive Care Unit: Opinions of Physicians at Three Teaching Hospitals. Southwest J Pulmonary and Critical Care 2015; 10: 34-43.
• Lighthall GK, Olejniczak M. Routine postoperative care of patients undergoing coronary artery bypass grafting on cardiopulmonary bypass. Seminars in Cardiothoracic and Vascular Anesthesia 2015; 19 (2):78-86.
• Lighthall G, Vazquez-Guillamet C. Decision-making in critical care medicine. Clinical Medicine and Research 2015; 13(3-4): 156-168
• Lighthall G, Verduzco L. Survival after long-term residence in an intensive care unit. Federal Practitioner 2016; June: 18-27.
• Bannard-Smith J, Lighthall GK, Jones DA, Subbe CP, Durham L, Welch J, Bellomo R, Subbe C for the Medical Emergency Team Hospital Outcomes in a Day (METHOD) investigators. Clinical outcomes of patients seen by Rapid Response Teams: A template for benchmarking international teams. Resuscitation. 2016 Jul 11;107:7-12.
• Maslove DM, Chen BT-M, Wang H, Kuschner WG. The diagnosis and management of pleural effusions in the ICU. J Intensive Care Med 2013;28:24-36
• Wang HL, Aguilera C, Knopf, KB, Chen T-M B, Maslove, DM, Kuschner WG. Thrombocytopenia in the intensive care unit. J Intensive Care Med 2013;28:268 - 80.
• Chen T-M B, Malli H, Maslove, DM, Wang H, Kuschner WG. Toxic inhalational exposures. J Intensive Care Med 2013;28: 323-33.
• Nguyen C, Kaku S, Tutera D, Kuschner WG, Barr J. Viral respiratory infections of adults in the intensive care unit. J Intensive Care Med 2016;31:427-41.
• Ho JQ, Nguyen CD, Lopes R, Ezeji-Okoye SC, Kuschner WG. Spiritual care in the intensive care unit: a narrative review. J Intensive Care Med, 2017 Jan 1:885066617712677. doi: 10.1177/0885066617712677. [Epub ahead of print]
• Sevransky JE, Checkley W, Herrera P, Pickering BW, Barr J*, Brown SM, Chang SY, Chong D, Kaufman D, Fremont RD, Girard TD, Hoag J, Johnson SB, Kerlin MP, Liebler J, O'Brien J, O'Keefe T, Park PK, Pastores SM, Patil N, Pietropaoli AP, Putman M, Rice TW, Rotello L, Siner J, Sajid S, Murphy DJ, Martin GS; United States Critical Illness and Injury Trials Group-Critical Illness Outcomes Study Investigators. Protocols and hospital mortality in critically ill patients: the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study (USCIITG-CIOS). Crit Care Med. 2015 Oct; 43(10):2076-84. (PMID: 26110488).
• Nguyen CD, Kaku S, Tutera D, Kuschner W, Barr J. Viral respiratory infections of adults in the intensive care unit. J Intensive Care Med. 2015 May 19. [Epub ahead of print] (PMID: 25990273)
• Mudumbai SC, Barr J, Scott J, Mariano ER, Bertaccini EJ, Nguyen HT, Memtsoudis SG, Cason B, Phibbs CS, Wagner T. Invasive mechanical ventilation in California over 2000-2009: Implications for emergency medicine. West J Emerg Med. 2015; 16(5):696-706. (PMID: 26587094)
• Gelinas C, Berube M, Chevrier A, Pun BT, Ely WE, Skrobik Y, Barr J. Delirium Assessment Tools for use in Critically Ill Adults: A Psychometric Analysis and Systematic Review. Critical Care Nurse (In Press – July 2017)
• Barnes-Daly MA, Pun BT, Harmon LA, Kumar VK, Schweickert WD, Engel HJ, Esbrook CL, Stollings JL, Hargett KD, Devlin JW, Carson SS, Aldrich JM, Posa PJ, Puntillo KA, Barr J, Byrum DG, Ely EW, Balas MC. Society of Critical Care Medicine’s ICU Liberation ABCDEF Bundle Improvement Collaborative: Background, Implementation Strategies, and Performance/Outcome Metrics. Critical Care Medicine (In Press)
• Hurt CM, Ho VK, and Angelotti, T. Systematic and quantitative analysis of G protein-coupled receptor trafficking motifs. Methods Enzymology P. Michael Conn, eds. Academic Press (2013) 521:171-187.
• Björk S, Hurt CM, Ho, VK, and Angelotti T. REEPs are membrane shaping adapter proteins that modulate specific G protein-coupled receptor trafficking by affecting ER cargo capacity. PLoS One (2013) 8:e76366.
• Hurt CM, Björk S, Ho VK, Gilsbach, R, Hein, L, and Angelotti T. REEP1 and REEP2 proteins are preferentially expressed in neuronal and neuronal-like exocytotic tissues. Brain Research (2014) 1545:12-22.
• Sorensen MW, Hurt CM and Angelotti T. Common alpha2 adrenergic receptor polymorphisms do not alter plasma membrane trafficking. Naunyn-Schmiedebergs Arch Pharmacol (2014) 387:569-579
• Hurt CM and Angelotti T. Expression and trafficking of functional G protein-coupled receptors are related, yet distinct, concepts. Naunyn-Schmiedebergs Arch Pharmacol (2014) 387:1009-1012
• Jafari A, Langen ES, Aziz N, Mihm F, Druzin ML: ‘The Effects of Respiratory Failure on Delivery in Pregnant Patients with H1N1 2009 Influenza’ Journal of Obstetrics and Gynecology 2010; 115:1033-1035
• Mayette M, Gonda J, Hsu JL, Mihm FG: “Propofol infusion syndrome resuscitation with extracorporeal life support: a case report and review of the literature” Annals of Intensive Care 2013; 3(1):32.
• Htet N, Vaughn J, Adigopula S, Hennessey E, Mihm F: “Needle-guided ultrasound technique for axillary artery catheter placement in critically ill patients: a case series and technique description” Journal of Critical Care 2017 (in press)
• Krishnamohan P, Lighthall G. Simulation for Training in Neuro Critical Care. in Shrestha, Ed., Manual of Neuroanesthesia and Neurocritical Care. Georg Thieme Verlag KG. Stuttgart, Germany in press
• Lighthall GK, Reid CS. Tissue oxygenation and cardiac output. Arbo J, Ed.: Decision Making in Emergency and Critical Care. Wolters Kluwer; Philadelphia, PA c. 2015; Chapter 2, pp. 6-17.
• Lantry J, Arbo JE, Lighthall GK. Thyroid Storm and Myxedema Coma. Arbo J, Ed.: Decision Making in Emergency and Critical Care. Wolters Kluwer; Philadelphia, PA c. 2015; Chapter 44, pp. 569-585.
• Lighthall GK, Arbo JE. Emergency Department Evaluation of the Critically Ill Patient. Arbo J, Ed.: Decision Making in Emergency and Critical Care. Wolters Kluwer; Philadelphia, PA c. 2015; Chapter 61, pp. 762-769.
• Lighthall G, Minimi NC, DeVita M. Simulation for teamwork training. Riley R, Ed. Manual of Simulation in Healthcare, 2nd Ed. Oxford University Press; Oxford, UK 2016. Chapter 25, pp. 345-355.
• Angelotti T and Lemmens H (2004) “Liver/Kidney Transplantation” in Anesthesiologist’s Manual of Surgical Procedures, 3rd ed. (eds. R. Jaffe and S. Samuels), pp.538-565, Lippincott Willliams and Wilkins (Philadelphia).
• Angelotti T and Lemmens H (2008) “Liver/Kidney/Pancreas Transplantation” in Anesthesiologist’s Manual of Surgical Procedures, 4th ed. (eds. R. Jaffe), pp.679-712, Lippincott Willliams and Wilkins (Philadelphia).
• Angelotti T (2011) “Anesthetic Pharmacology of the Autonomic Nervous System” in The Neuroscientific Foundations of Anesthesiology, 1st ed. (eds. G. Mashour and R. Lydic), pp. 186-201, Oxford University Press (New York).
• Angelotti T and Lemmens H (2014) “Liver/Kidney/Pancreas Transplantation” in Anesthesiologist’s Manual of Surgical Procedures, 5th ed. (eds. R. Jaffe), pp. 693-726, Lippincott Willliams and Wilkins (Philadelphia).
• Kuschner W Paintal HS. History of air pollution. In: Friis RH (ed.) Praeger Handbook of Environmental Health volume 3. Praeger: Santa Barbara, California, 2012, pp. 143-163.
• Paintal HS, Kuschner WG. Natural sources of air pollution. In: Friis RH (ed.) Praeger Handbook of Environmental Health volume 3. Praeger: Santa Barbara, California, 2012, pp. 165-184.
• Ho L, Kuschner WG. Hypersensitivity pneumonitis. In:Huang Y-C T, Ghio AJ, Maier LA (eds.). A Clinical Guide to Occupational and Environmental Lung Diseases. Humana Press: New York, NY, 2012, pp. 113-132.
• Kuschner WG, Blanc PD. Gases and other airborne toxicants. In: LaDou J and Harrison R (eds.) Current Diagnosis & Treatment in Occupational & Environmental Medicine, 5/e. McGraw Hill: 2014, pp. 557-572.
• Kuschner WG, Blanc PD. Occupational and Environmental Conditions. In: Baliga RR (ed). Textbook of Internal Medicine--An Intensive Board Review with 1000 MCQs. Blendon-Miller. in press
• Rudolf U, Davies MF, Barr J. Benzodiazepines. In: Evers AS, Maze M, Kharasch E, editors. Anesthetic Pharmacology. 2nd ed. Cambridge, UK: Cambridge University Press; 2011. P. 466-477.
• Barr J. Liberating ICU Patients from Deep Sedation and Mechanical Ventilation-What’s New since the ICU PAD Guidelines? In: Clemmer T, Balas M, Hargett K, editors. ICU Liberation: The Power of Pain Control, Minimal Sedation, and Early Mobility. Mount Prospect, IL: Society of Critical Care Medicine; 2015. p. 13-29.
• Barr J, Sauer W. Reversal Agents: Naloxone, Flumazenil, and Sugammadex. In: FLEISHER LA, editor. Complications in Anesthesia. 3rd ed. Philadelphia, PA: Elsevier; (in press).
• Tenaka P, Mihm FG: “Lower leg, ankle, foot, and other lower extremity procedures” The Anesthesiologist’s Manual of Surgical Procedures. Jaffe RJ, Samuels S, Eds, Lippincott, Philadelphia, 2013
• Tenaka P, Mihm FG: “Knee surgery” The Anesthesiologist’s Manual of Surgical Procedures. Jaffe RJ, Samuels S, Eds, Lippincott, Philadelphia, 2013
• Scotto L, Citron L, Mihm FG, Nekendzy V: “Airway Ultrasonography and Its Clinical Application to Airway Management” Head and Neck Ultrasonography 2nd Edition. Orloff LA, Ed, Plural Publishing, Inc, 2017, pp283-304.
• Lyons A., Mihm F “ Ankle Block” Reconstructive and Plastic Surgery (in press) 2017
• Steckelberg RC, Mihm F, Derby R “Regional Anesthesia“ in ¬¬Global Reconstructive Surgery (in press) 2017
• Olejniczak M and Lighthall G. Safer tracheostomy: proposal for routine use of an airway exchange catheter during tracheostomy. Anesthesia and Analgesia Case Reports. 2014; 3: 146-8.
• Lighthall G and Pollard J. A rare cause of patient movement occurring during carotid surgery. Anesthesia and Analgesia Case Reports 2015; 5: 1-2.
• Li CG, Roberts K, Lighthall G. Endotracheal tube clogging resulting in pulseless electrical activity cardiac arrest: revisiting the importance of confirming tube positioning—a case report, review of literature, and optimizing patient safety. J Anesth and Crit Care Case Reports 2016; 2:15-17
• Hilton G, Butwick A, Mihm F “Anesthetic Management of a Parturient with VACTERL Association Undergoing Cesarean Delivery” Canadian Journal of Anesthesia 2013; DOI 10.1007/s12630-013-9919-5 (case report)
• Tan M, Mihm FG; "Malignant Pheochromocytoma Presenting as Incapacitating Bony Pain" Pain Practice 2012; 12(4): 286-9 (case report) Tsai T, Barot N, Dalman R, Mihm F: "Combined Endovascular and Open Operative Approach for Mycotic Carotid Aneurysm" Journal of Vascular Surgery 2010; 51:1514-1516 (case report)
• Maslove D, Mihm FG: “Ultrasound-Guided Internal Jugular Vein Catheterization” New England Journal of Medicine 2010;363; 8:796. (letter) Maxwell BG, Mihm FG: “Questioning diuretic use in acute negative-pressure pulmonary edema” Anesthesiology 2011; 114 (2): 461 (letter)
• J. Florindez, R. Vazquez Guillamet, C. Vazquez Guillamet, C. Manthous, G. Lighthall. (2012) Physicians Perceptions of The Utility Of Physical Exam In The Intensive Care Unit. A Qualitative Study. American Thoracic Society International Conference, San Francisco, CA May, 2012
• Lighthall G, Verduzco L. Survival and Quality of Life Associated with ICU Residence in a United States Veteran Population. American Society of Anesthesiologists annual meeting 2013, oral poster presentation. San Francisco, CA. October 2013.
• Lighthall G, Mayette M. Impact of Continuous Monitoring at Various Times of Day on In-Hospital Cardiac Arrest Mortality. American Society of Anesthesiologists annual meeting 2013. San Francisco, CA. October, 2013.
• Perez F, Howard SK, King R, Mariano E, Lighthall G, Harrison K. Survival and Neurological Outcomes of Cardiac Arrests at a University-Affiliated Veterans Affairs Health Care System. Stanford Quality Improvement and Patient Safety Symposium. June 8, 2015. (Top 10 award).
• Villar J, Lighthall G. Serum lactate predicts 3-day, 30-day and 1-year mortality in unselected inpatients. Annual Congress of the Society of Critical Care Medicine. Jan 20, 2017. Honolulu, HA. Critical Care Medicine 2016; 44 (12, suppl.): A 333. (First place, database research. Stanford Anesthesiology dept. research meeting; First place research award, Calif. Society of Anesthesiologists Annual meeting 2017).
• Angelotti T, Ho V, and Hurt C. REEPs, an ER adapter protein family, have differential effects on GPCR expression. The FASEB J. (2012) 26: 837.2. Presented at the Experimental Biology Meeting, San Diego, CA, April 2012.
• Angelotti T, Ho V, Björk S, and Hurt CM. Analysis of REEP mRNA and protein expression in neuronal and non-neuronal cells and cell lines. Program No. 653.20. 2012 Neuroscience Meeting Planner. Presented at the 42nd Society for Neuroscience Annual Meeting, New Orleans, LA: Society for Neuroscience, 2012.
• Hurt CM and Angelotti T. Single cell analysis of G protein-coupled receptor expression and trafficking to investigate disease pathogenesis. Program No. A1169. Abstract presented at the IARS 2015 Annual Meeting, Honolulu, HI, March 2015.
• Tipirneni, N, Valdiconza, C, Vora, M and Angelotti T. Sugammadex-associated anaphylaxis. Crit Care Med 44(12) (Supplement 1):490, Presented at the SCCM 46th Critical Care Congress, Honolulu, HI, January 2017.
• Sharma, B and Angelotti T. Acute embolic stroke due to a rare cause: Streptococcus constellatus endocarditis. Crit Care Med 44(12) (Supplement 1):523, Presented at the SCCM 46th Critical Care Congress, Honolulu, HI, January 2017.
• Eskandari M, Kuschner WG, Kuhl E. A Personalized mechanical model of chronic lung disease. Biomedical Engineering Society Annual Meeting, October 7-10, 2015 in Tampa, Florida.
• V.S. Nair, MD MS, J. Rosenberg, PhD, G. Horng, M.D., , M. Jamali, MBBS, P. Tripathi, MBBS, A. Iagaru, MD, W. Kuschner, MD, M. Vasanawala, MD, S.S. Gambhir, MD PhD Does the White Blood Cell Count Assist with Solitary Pulmonary Nodule Diagnosis [Publication Page: A3565] May 18, 2015.
• Breiburg A, Lam K, Nicolls M, Dhillon G, Zone C, Kuschner W. Impact of non-invasive open ventilation (NIOV) on dyspnea and quality of life in patients with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). American Thoracic Society International Conference, 2016.
• V. Nair, F. Carlsson, A. Carlsson, M. Jamali, K. Keu, M. Vasanawala, J. Shrager, B. Loo, G. Horng, W. Kuschner, S. Gambhir, P. Kuhn FDG PET-CT SUVmax and Circulating Tumor Microemboli Identify Recurrence in Patients with Non-Small Cell Lung Cancer. American Thoracic Society International Conference, May 21, 2017.
• K. Lam, A. Breiburg, W. Kuschner, C. Zone, G. Dhillon, Long-term impact of Non Invasive Open ventilation (NIOB) on Dyspnea with Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis. American Thoracic Society International Conference, May 23, 2017.
• Barr J, Sani O, Davies MF, Tanaka T, Geller, E. Dexmedetomidine for ICU sedation: A retrospective study. Crit Care Med, December 2007; Suppl 35(12): A246.
• Bui Y, Barr J, Hasson N, O’Leary-Kelly C, Miyahara R. The efficacy and safety of implementing a glycemic control protocol in ICU patients. Crit Care Med, December 2007; Suppl 35(12):A135.
• Mudumbai SC, Barr J, Upadhyay A, Heidenreich P, Bertaccini EJ, Phibbs CS, Mariano ER, Cason B, Wagner T. Patterns of Invasive Mechanical Ventilation Usage among Different Age Strata in California from 2000-2009.ANESTHESIOLOGY 2012; SupplA704
• Rao V, Hennessey E, Russell I, Deitz J, Barr J. Validation Strategy for Developing a Critical Care Medicine Clerkship Examination for Medical Students. Proceedings, Anesthesiology 2013, American Society of Anesthesiologists Annual Meeting, Oct. 12-16, 2013, San Francisco, CA.
• Mudumbai SC, Barr J, Scott J, Bertaccini EJ, Nguyen HT, Phibbs CS, Mariano ER, Cason B, Wagner T. Costs of Invasive Mechanical Ventilation among Different Age Strata. Proceedings, Anesthesiology 2013, American Society of Anesthesiologists Annual Meeting, Oct. 12-16, 2013, San Francisco, CA.

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Research into the problems of critically ill patients is investigated at the clinical and molecular level. The focus of our research is to improve our ability to care for patients with life-threatening disorders. Please click on faculty members below to view current research and publication history.

• Timothy P. Angelott, MD, PhD   Dr. Angelotti is interested in the molecular basis for sympathetic axtivation and modulation in various disease states.
• Edward J. Bertaccini MD Dr. Bertaccini is interested in the molecular mechanisms of anesthesia and sedation in the intensive care unit.
• Ware Kuschner, MD   Dr. Kushner's research focuses on health effects of toxic inhalational exposure.
• Geoff Lighthall, MD Dr. Lighthall is interested in the evolution of critical illnesses and its detection at a stage where intensive care can produce meaningful results. Prior work has focused on vital signs and monitoring as means of detecting deterioration as well as the development of medical emergency teams (RRTs) to deliver rapid care to unstable patients. Fellows have enjoyed working on these projects as well as those looking at the survival and function of critically ill patients seen by emergency teams and cared for in the ICU. Additionally, Dr. Lighthall is a leader in the use of simulation systems in critical care team training and as a means of evaluating care delivery systems.
• Fred Mihm, MD   Dr. Mihm’s two areas of research interest involve cardiorespiratory monitoring techniques and applications and the perioperative management of patients with pheochromocytoma.

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Major Bleeding in Adults Undergoing Peripheral Extracorporeal Membrane Oxygenation (ECMO): Prognosis and Predictors

Background. Major bleeding has been a common and serious complication with poor outcomes in ECMO patients. With a novel, less-invasive cannulation approach and closer coagulation monitoring regime, the incidence of major bleeding is currently not determined yet. Our study aims to examine the incidence of major bleeding, its determinants, and association with mortality in peripheral-ECMO patients. Method. We conducted a single-center retrospective study on adult patients undergoing peripheral-ECMO between January 2019 and January 2020 at a tertiary referral hospital. Determinants of major bleeding were defined by logistic regression analysis. Risk factors of in-hospital mortality were determined by Cox proportional hazard regression analysis. Results. Major bleeding was reported in 33/105 patients (31.4%) and was associated with higher in-hospital mortality [adjusted hazard ratio (aHR) 3.56, 95% confidence interval (CI) 1.63–7.80, p < 0.001 ). There were no significant difference in age, sex, ECMO indications, ECMO modality, pre-ECMO APACHE-II and SOFA scores between two groups with and without major bleeding. Only APTT >72 seconds [adjusted odds ratio (aOR) 7.10, 95% CI 2.60–19.50, p < 0.001 ], fibrinogen <2 g/L [aOR = 7.10, 95% CI 2.60–19.50, p < 0.001 ], and ACT >220 seconds [aOR = 3.9, 95% CI 1.20–11.80, p = 0.017 ] on days with major bleeding were independent predictors. Conclusions. In summary, major bleeding still had a fairly high incidence and poor outcome in peripheral-ECMO patients. APTT > 72 seconds, fibrinogen < 2 g/L were the strongest predicting factors for major bleeding events.

Incidence and Risk Factors of Ventilator-Associated Pneumonia among Patients with Delirium in the Intensive Care Unit: A Prospective Observational Study

Introduction. The incidence and risk factors for ventilator-related pneumonia (VAP) in patients with delirium are deficient, and there is a lack of in-depth knowledge of the impact of VAP on outcomes in this population. We investigated the incidence, risk factors, and outcomes of VAP in patients with delirium. Materials and Methods. This prospective observational study was performed in a surgical ICU at Be’sat Hospital in Hamadan, Iran, between 2018 and 2019. A total of 108 patients with delirium were identified using the Confusion Assessment Method (CAM) for the ICU and Intensive Care Delirium Screening Checklist (ICDSC) and enrolled in this study. The association between VAP and delirium, risk factors, and outcomes (ICU length of stay and ICU mortality) for VAP were investigated using the Cox proportional hazards model and logistic and simple linear regression analyses with a 95% confidence interval. Results. Of 108 delirium patients, 86 patients (79.6%) underwent mechanical ventilation (MV) and 16 patients (18.6%) experienced VAP during ICU stay. The median onset of VAP was 6.5 (IQR 4.2–7.7) days after intubation. Delirium patients with VAP stayed longer in the ICU (21.68 ± 4.26 vs.12.93 ± 1.71, P < 0.001 ) and also had higher ICU mortality (31.25% vs. 0%, P < 0.001 ) than subjects without VAP. According to multivariate cox regression, the expected HR for VAP was 53.5% lower for patients with early-onset delirium than in patients with late-onset delirium (HR: 0.465, 95% CI: 0.241–0.894, P = 0.022 ). However, the expected hazard for VAP was 1.854 times and 4.604 times higher in patients with longer ICU stay (HR: 1.854, 95% CI: 1.689–3.059, P = 0.032 ) and in patients with a prolonged MV duration (HR: 4.604, 95%CI: 1.567–6.708, P = 0.023 ). Conclusion. According to the results, there seems to be an inverse relationship between early onset of delirium and VAP. This finding cannot be conclusively cited, and more studies in this filed should be conducted with a larger sample size. Furthermore, VAP in delirium patients is associated with increases in poor outcomes (higher ICU mortality) and the use of medical resources (longer stay in the ICU and MV duration).

Characteristics of Adult Sepsis Patients in the Intensive Care Units in a Tertiary Hospital in Jordan: An Observational Study

Sepsis is a global health issue that is commonly encountered in the intensive care unit (ICU) and is associated with high morbidity and mortality. Available data regarding sepsis in low- and middle-income countries (LMIC) is lacking compared to higher income countries, especially using updated sepsis definitions. The lack of recent data on sepsis in Jordan prompted us to investigate the burden of sepsis among Jordanian ICU patients. We conducted a prospective cohort study at Jordan University Hospital, a tertiary teaching hospital in the capital, Amman. All adult patients admitted to the adult ICUs between June 2020 and January 2021 were included in the study. Patients’ clinical and demographic data, comorbidities, ICU length of stay (LOS), medical interventions, microbiological findings, and mortality rate were studied. Descriptive and inferential statistics were used to analyse data from patients with and without sepsis. We observed 194 ICU patients during the study period; 45 patients (23.3%) were diagnosed with sepsis using the Sepsis-3 criteria. Mortality rate and median ICU LOS in patients who had sepsis were significantly higher than those in other ICU patients (mortality rate, 57.8% vs. 6.0%, p value < 0.001, resp., and LOS 7 days vs. 4 days, p value < 0.001, resp.). Additionally, sepsis patients had a higher combined number of comorbidities (2.27 ± 1.51 vs. 1.27 ± 1.09, p value < 0.001). The use of mechanical ventilation, endotracheal intubation, and blood transfusions were all significantly more common among sepsis patients. A causative organism was isolated in 68.4% of sepsis patients with a prevalence of Gram-negative bacteria in 77.1% of cases. While the occurrence of sepsis in the ICU in Jordan is comparable to other regions in the world, the mortality rate of sepsis patients in the ICU remains high. Further studies from LMIC are required to reveal the true burden of sepsis globally.

Influence of Spontaneous and Mechanical Ventilation on Frequency-Based Measures of Heart Rate Variability

Frequency-based measures of heart rate variability have been shown to be a useful physiological marker in both clinical and research settings providing insight into the functioning of the autonomic nervous system. Ongoing interactions between the autonomic nervous system control of the heart and lung occurs during each ventilation cycle because of their anatomical position within the closed thoracic cavity. Mechanical ventilation and subsequent removal change the normal ventilator mechanics producing alterations in the tidal volume, intrathoracic pressure, and oxygen delivery. A noninvasive method called heart rate variability (HRV) can be used to evaluate this interaction during ventilation and can be quantified by applying frequency-based measures of the variability between heartbeats. Although HRV is a reliable method to measure alteration of the autonomic nervous system (ANS) function and cardiopulmonary interaction, there have been limited reports concerning the changes in the frequency-based measure of HRV during both spontaneous and mechanical ventilation. The purpose of this methodological study is therefore to describe the physiological influence of both spontaneous and mechanical ventilation on frequency-based measures of HRV.

Prevalence and Trajectory of COVID-19-Associated Hypercoagulability Using Serial Thromboelastography in a South African Population

Introduction. The coagulation abnormalities resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been attributed to inflammation and subsequent cytokine storm. Thromboelastography (TEG) is a point-of-care test used to assess clot formation and degradation in whole blood and is an indicator of the overall real-time coagulopathic state of the patient. Methods. A single-centre, prospective, observational cohort study was conducted in South Africa, analysing the coagulation patterns of 41 patients with hypoxia related to SARS-CoV-2 using serial thromboelastography (TEG) on admission, after 48 hours, and at resolution of hypoxia/day 10. Results: Two-thirds (n = 26) were women. The median age was 61 (IQR 50–67), and the majority (88%) were Black patients. Almost half (22) of the patients were critically ill and ventilated, with median SOFA and SAPS2 scores of 3 and 22 (IQR2-4 and 18–30), respectively. The prevalence of hypercoagulability was 0.54 (95% CI 0.46–0.62), whilst 29/41 (0.71, CI 0.64–0.78)) met the definition of hypofibrinolysis. Differences between the hypercoagulable (HC) and non-hypercoagulable groups remained apparent at 48 hours after anticoagulation. At this time point, the K time was significantly lower ( p  ˂ 0,01), and the α-angle ( p  ˂ 0,01) and maximum amplitude (MA) ( p  ˂ 0,01) were significantly higher in the HC cohort. At resolution of hypoxia, or day 10, only MA was significantly higher in the hypercoagulable group compared to the non-hypercoagulable group (p = 0.01). The initial impairment in fibrinolysis (Ly30), α angle, and MA were significantly associated with mortality, with p values of 0.006, 0.031, and 0.04, respectively. Conclusions. In this South African population, hypercoagulability was a highly prevalent phenomenon in COVID-19 disease. It was typified by hypofibrinolysis and a persistently elevated MA, despite anticoagulation therapy.

Use of mNUTRIC-Score for Nutrition Risk Assessment and Prognosis Prediction in Critically Ill Patients with COVID-19: A Retrospective Observational Study

Introduction. Nutritional risk is highly prevalent in patients with COVID-19. Relevant data on nutritional assessment in the critically ill population are scarce. This study was conducted to evaluate the modified Nutrition Risk in the Critically Ill (mNUTRIC)-Score as a mortality risk factor in mechanically ventilated patients with COVID-19. Methods. We conducted this retrospective observational study in critically ill patients with COVID-19. Patients’ characteristics and clinical information were obtained from electronic medical records. The nutritional risk for each patient was assessed at the time of mechanical ventilation using the mNUTRIC-Score. The major outcome was 28-day mortality. Results. Ninety-eight patients were analyzed (mean age, 57.22 ± 13.66 years, 68.4% male); 46.9% of critically ill COVID-19 patients were categorized as being at high nutrition risk (mNUTRIC-Score of ≥5). A multivariate logistic regression model indicated that high nutritional risk has higher 28-day hospital mortality (OR = 4.206, 95% CI: 1.147–15.425, p = 0.030 ). A multivariate Cox regression analysis showed that high-risk mNUTRIC-Score had a significantly increased full-length mortality risk during hospitalization (OR = 1.991, 95% CI: 1.219–3.252, p = 0.006 ). Conclusion. The mNUTRIC-Score is an independent mortality risk factor during hospitalization in critically ill COVID-19 patients.

Assessment of Metabolic Dysfunction in Sepsis in a Retrospective Single-Centre Cohort

Objective. Our primary aim was to assess selected metabolic dysfunction parameters, both independently and as a complement to the SOFA score, as predictors of short-term mortality in patients with infection admitted to the intensive care unit (ICU). Methods. We retrospectively enrolled all consecutive adult patients admitted to the eight ICUs of Lille University Hospital, between January 2015 and September 2016, with suspected or confirmed infection. We selected seven routinely measured biological and clinical parameters of metabolic dysfunction (maximal arterial lactatemia, minimal and maximal temperature, minimal and maximal glycaemia, cholesterolemia, and triglyceridemia), in addition to age and the Charlson’s comorbidity score. All parameters and SOFA scores were recorded within 24 h of admission. Results. We included 956 patients with infection, among which 295 (30.9%) died within 90 days. Among the seven metabolic parameters investigated, only maximal lactatemia was associated with higher risk of 90-day hospital mortality in SOFA-adjusted analyses (SOFA-adjusted OR, 1.17; 95%CI, 1.10 to 1.25; p < 0.001 ). Age and the Charlson’s comorbidity score were also statistically associated with a poor prognosis in SOFA-adjusted analyses. We were thus able to develop a metabolic failure, age, and comorbidity assessment (MACA) score based on scales of lactatemia, age, and the Charlson’s score, intended for use in combination with the SOFA score. Conclusions. The maximal lactatemia level within 24 h of ICU admission is the best predictor of short-term mortality among seven measures of metabolic dysfunction. Our combined “SOFA + MACA” score could facilitate early detection of patients likely to develop severe infections. Its accuracy requires further evaluation.

Diabetic Ketoacidosis Updates: Titratable Insulin Infusions and Long-Acting Insulin Early

Background. To compare a titratable insulin infusion order set (vs. nontitratable) and early administration of long-acting insulin in adult patients with diabetic ketoacidosis (DKA). Methods. Single health system, retrospective study of adult patients admitted to the intensive care unit (ICU) for DKA. The primary outcomes were insulin infusion duration and ICU/hospital length of stays (LoS). Secondary outcomes included ICU/hospital survival, hypoglycemia, and hypokalemia. Results. 151 patients were included in the titratable versus nontitratable insulin infusion comparison. Patients treated with the titratable insulin had shorter hospitalization (6.4 vs. 10.4 days, p = 0.03 ) and reduced the number hypoglycemic events by over half (20.6% vs. 46.0%, p < 0.01 ). 110 patients were identified to compare overlapping a long-acting insulin for more than 4 h with the insulin infusion versus the standard 1-2 h overlap. Patients who received the insulin early spent over 18 h longer on the infusion ( p < 0.01 ). Conclusions. A titratable insulin infusion added to the institutional DKA order set was associated with fewer days in the hospital and a significant reduction in hypoglycemic events. Furthermore, overlapping the long-acting insulin earlier with the insulin infusion early showed no benefit and could potentially be worse than the standard overlap.

Correlation of Serum Albumin Level to Lung Ultrasound Score and Its Role as Predictors of Outcome in Acute Respiratory Distress Syndrome Patients: A Prospective Observational Study

Background. There is ambiguity in the literature regarding hypoalbuminemia as a cause of extravascular lung water and acute respiratory distress syndrome (ARDS) outcomes. The aim of the study was to determine if low serum albumin on admission leads to lung deaeration and higher lung ultrasound score (LUSS) in ARDS patients. Patients and Methods. It was a prospective observational study in which 110 ARDS patients aged between 18 and 70 years were recruited. Serum albumin level and lung ultrasound score were assessed on the day of ICU admission. Length of ICU stay and hospital mortality were recorded. Results. The mean and standard deviation of serum albumin level in mild, moderate, and severe ARDS was 2.92 ± 0.65 g/dL, 2.91 ± 0.77 g/dL, and 3.21 ± 0.85 g/dL, respectively. Albumin level was not correlated to the global LUSS (Pearson correlation r −0.006, p = 0.949 ) and basal LUSS (r −0.066, p = 0.513 ). The cut-off value of albumin for predicting a prolonged length of ICU stay (≥10 days) in ARDS patients was <3.25 g/dL with AUC 0.623, p < 0.05 , sensitivity of 86.67%, specificity of 45.45%, and 95% confidence interval (CI) [0.513–0.732], and on multivariate analysis it increased the odds of prolonged ICU stay by 8.9 times (Hosmer and Lemeshow p value 0.810, 95% CI [2.760–28.72]). Serum albumin at admission was not a predictor of mortality. LUSS on the day of admission was not useful to predict either a prolonged length of ICU stay or mortality. Basal LUSS contributed about 56% of the global LUSS in mild and moderate ARDS, and 53% in severe ARDS. Conclusion. Serum albumin level was unrelated to LUSS on admission in ARDS patients. Albumin level <3.25 g/dL increased the chances of a prolonged length of ICU stay (≥10 days) but was not associated with an increase in mortality. LUSS on the day of admission could not predict either a prolonged length of ICU stay or mortality. This trial is registered with CTRI/2019/11/021857.

Knowledge, Attitude, and Associated Factors towards Nonpharmacological Pain Management among Nurses Working at Amhara Region Comprehensive Specialized Hospitals, Ethiopia

Background. Nonpharmacological pain management refers to providing pain management intervention that does not involve the use of drugs. Effective management of a patient’s pain is a vital nursing activity, and it needs a nurse’s adequate pain-related knowledge and a favorable attitude. Globally, many studies stated that the lack of knowledge and unfavorable attitude of nurses towards nonpharmacological pain management was the prevailing persistent challenge. Objective. To assess knowledge, attitude, and associated factors towards nonpharmacological pain management among nurses working in Amhara region Comprehensive Specialized Hospitals, Ethiopia, 2021. Method. An institutional-based cross-sectional study was conducted from April to May 30, 2021. A total of 845 nurses were selected using a simple random sampling technique. Data were collected by using a pretested self-administered structured questionnaire. Then, data were checked, coded, and entered into Epi Info version 7.0 and exported to SPSS version 25.0 software for analysis. Results. A total of 775 nurses participated in this study, with a response rate of 91.8%. Of the total participants, 54.2% (95% CI: 50.6–57.9) and 49.8% (95% CI: 46.1–53.2) of nurses had adequate knowledge and a favorable attitude, respectively. The study revealed that educational status (AOR = 3.51 (95% CI: 1.37, 8.99)), years of experience (AOR = 5.59 (95% CI: 2.86, 10.94)), working unit (AOR = 5.61 (95% CI: 2.25, 13.96)), nurse-to-patient ratio (AOR = 2.33 (95% CI: 1.44, 3.78)), and working hours (AOR = 2.15 (95% CI: 1.27, 3.62)) were significantly associated. This finding also revealed that monthly income (AOR = 4.38 (95% CI: 1.64, 11.69)), nurse-to-patient ratio (AOR = 1.89 (95% CI: 1.19, 3.01)), and nurses’ adequate knowledge (AOR = 4.26 (95% CI: 2.91, 6.24)) were significantly associated with the attitude of nurses. Conclusion and Recommendations. More than half and nearly half of the nurses had adequate knowledge and a favorable attitude towards nonpharmacological pain management, respectively. Educational qualification, years of experience, working unit, nurse-to-patient ratio, and prolonged working hours per day were significantly associated with nurse’s adequate knowledge. Monthly income, nurse-to-patient ratio, and nurse’s knowledge were significantly associated with the attitudes of nurses. It is better to give attention to reviewing the nursing curriculum, achieving a standardized nurse-to-patient ratio, recruiting additional nurses, training, and upgrading nurses with continuing education.

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Correlation between worsening pneumonitis and right ventricular systolic function in critically ill patients with COVID-19

• Hazem Lashin 1 , 2 ,
• Jonathan Aron 3 ,
• Shaun Lee 3 &
• Nick Fletcher 3 , 4  

Echo Research & Practice volume  11 , Article number:  19 ( 2024 ) Cite this article

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The pneumonitis associated with coronavirus disease 2019 (COVID-19) infection impacts the right ventricle (RV). However, the association between the disease severity and right ventricular systolic function needs elucidation.

We conducted a retrospective study of 108 patients admitted to critical care with COVID-19 pneumonitis to examine the association between tricuspid annular plane systolic excursion (TAPSE) by transthoracic echocardiography as a surrogate for RV systolic function with PaO 2 /FiO 2 ratio as a marker of disease severity and other respiratory parameters.

The median age was 59 years [51, 66], 33 (31%) were female, and 63 (58%) were mechanically ventilated. Echocardiography was performed at a median of 3 days [2, 12] following admission to critical care. The PaO 2 /FiO 2 and TAPSE medians were 20.5 [14.4, 32.0] and 21 mm [18, 24]. There was a statistically significant, albeit weak, association between the increase in TAPSE and the worsening of the PaO 2 /FiO 2 ratio (r 2  = 0.041, p  = 0.04). This association was more pronounced in the mechanically ventilated (r 2  = 0.09, p  = 0.02). TAPSE did not correlate significantly with FiO 2 , PaO 2 , PaCO 2 , pH, respiratory rate, or mechanical ventilation. Patients with a TAPSE ≥ 17 mm had a considerably worse PaO 2 /FiO 2 ratio than a TAPSE < 17 mm (18.6 vs. 32.1, p  = 0.005). The PaO 2 /FiO 2 ratio predicted TAPSE (OR = 0.94, p  = 0.004) with good area under the curve (0.72, p  = 0.006). Moreover, a PaO 2 /FiO 2 ratio < 26.7 (moderate pneumonitis) predicted TAPSE > 17 mm with reasonable sensitivity (67%) and specificity (68%).

In patients admitted to critical care with COVID-19 pneumonitis, TAPSE increased as the disease severity worsened early in the course of the disease, especially in the mechanically ventilated. A TAPSE within the normal range is not necessarily reassuring in early COVID-19 pneumonitis.

Introduction

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), often leads to pneumonitis and significantly increased admissions to hospitals and critical care units worldwide [ 1 ]. The increase in critical care admissions is attributed to respiratory compromise that requires support, ranging from additional oxygen to invasive mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Also, COVID-19 often leads to dysfunction in other organs, particularly the heart and kidneys. In cases where multiple organs are affected, the risk of mortality due to COVID-19 is higher [ 2 ].

COVID-19 adversely affects the heart in two ways [ 3 , 4 ]. Firstly, it can directly affect the myocardium. Second, it can lead to complications arising from severe lung disease, which often result in right ventricular (RV) dysfunction. These adverse effects may lead to potentially life-threatening hemodynamic instability and cardiogenic shock. In grave cases, mechanical circulatory support is necessary to sustain life. Ensuring close observation and timely intervention for patients with RV dysfunction is paramount as they are at a significantly elevated mortality risk [ 3 , 4 , 5 , 6 ].

Several factors may lead to RV dysfunction in COVID-19 patients. Hypoxia caused by pneumonitis can directly affect the RV and reduce its systolic function [ 7 ]. However, this group’s main reason for dysfunction is the rise in RV afterload [ 3 ]. Severe inflammation induced by SARS-COV-2 can lead to pulmonary vascular dysfunction and increased resistance. COVID-19 can also cause micro- or macro emboli in the pulmonary circulation, leading to increased pulmonary artery pressure. In mechanically ventilated patients, high ventilatory pressures required for adequate gas exchange can further increase pulmonary artery pressure. When combined, these factors may cause acute pulmonary hypertension and RV dysfunction.

Studies have demonstrated that COVID-19 patients in critical care may exhibit one or more echocardiographic features of RV dysfunction [ 4 , 5 ]. These features include impaired RV systolic function. However, the relationship between the severity of illness and RV dysfunction has yet to be established.

We hypothesised that, as COVID-19 pneumonitis worsens, RV systolic function declines in patients admitted to critical care for respiratory support. To test our hypothesis, we conducted a retrospective single-centre cohort study that examined the association between the PaO 2 /FiO 2 ratio as a marker of the COVID-19 pneumonitis severity and tricuspid annular plane systolic excursion (TAPSE), using transthoracic echocardiography (TTE) as a surrogate for RV systolic function. We also investigated the correlation between TAPSE and other commonly measured respiratory parameters.

Materials and methods

Data collection.

We retrospectively reviewed consecutive patients admitted to our tertiary adult intensive care unit and diagnosed with COVID-19 pneumonitis between the 1st of February 2020 and the 28th of February 2021. Recent guidelines were used for data collection [ 8 ]. A secure web-based platform (REDCap) was used to collect and manage anonymised data [ 4 ]. The study received local research governance approval and followed the guidelines of the Declaration of Helsinki.

Patients and clinical data

Patients diagnosed with COVID-19 pneumonitis were admitted to the critical care unit for advanced respiratory support between the 1st of February 2020 and the 28th of February 2021. Support was protocolised for spontaneously breathing patients to facemask continuous positive pressure ventilation (CPAP) of 10 cmH 2 O or 15 cmH 2 O if the body mass index (BMI) was > 35. The patients who required further support were mechanically ventilated. Demographic and clinical data that could aid in echocardiographic interpretation were collected. The collected data included age, sex, body mass index (BMI), arterial blood gases, ventilation mode and parameters, cardiovascular parameters, and outcomes. Patients were included in the study if TAPSE and PaO 2 /FiO 2 ratios were available.

• Echocardiography

TTE studies were performed on all patients admitted to critical care with COVID-19 pneumonitis by critical care physicians trained and experienced in echocardiography and interpreted offline by accredited study team members (European Diploma in Advanced Critical Care Echocardiography [EDEC], British Society of Echocardiography level 2 or equivalent). All reviewers were blinded to the clinical parameters of the study. Data on LV ejection fraction (LVEF), LV size by visual estimation, tricuspid annular plane systolic excursion (TAPSE), RV size by visual estimation, and tricuspid regurgitation maximum velocity (TR Vmax) were collected. TAPSE was measured by M-Mode in an RV-focused view. A chamber was considered significantly dilated if classified as moderately or more dilated.

The primary endpoint of this study was the association between RV systolic function indicated by TASPE and the PaO 2 /FiO 2 ratio as a marker for COVID-19 pneumonitis disease severity. The secondary endpoint was the association between TAPSE and other respiratory parameters.

Statistical analysis

Continuous parameters were presented as median and interquartile range [IQR] and compared using the Mann-Whitney U test. Categorical data are presented as numbers, and percentages were compared using the chi-squared test. We tested correlations between continuous parameters using simple linear regression and correlations between continuous and categorical parameters using simple logistic regression. Linear regression analysis results are presented as r 2 , whereas those of the logistic regression analysis are presented as odds ratios (OR) and 95% confidence intervals (CI). The receiver operator curve (ROC) was used to investigate the efficacy of regression, and the results were presented as an area under the curve (AUC). In addition, ROC analysis allowed the identification of cutoffs with the best sensitivity and specificity for regression. A statistical analysis plan was defined before the analysis, and missing data were not imputed. Statistical analyses were performed using GraphPad Prism version 10 for the MacOS software package (GraphPad Software, San Diego, California, USA), and statistical significance was set at p  < 0.05.

Two-hundred and sixty-seven consecutive patients were admitted to our critical care unit with a diagnosis of COVID-19 pneumonitis and underwent echocardiography. A total of 119 patients were excluded from the study due to the unavailability of TAPSE data, followed by the exclusion of an additional 40 patients due to the unavailability of the PaO 2 /FiO 2 ratio. Thus, 108 patients were included in the analysis (Fig.  1 ).

CONSORT diagram for patient inclusion and exclusion. COVID-19: coronavirus disease 2019, ICU: intensive care unit, TAPSE: tricuspid plane systolic excursion

The median age was 59 years [51, 66], 33 (32%) were female, and 63 (58%) were mechanically ventilated at the time of echocardiography (Table  1 ). The median PaO 2 /FiO 2 ratio was in the moderate range (20.5 [14.4, 32.0]) for acute respiratory distress syndrome (ARDS). Echocardiography was performed at a median of 3 days [ 2 , 12 ] following admission to critical care. Echocardiograms revealed LVEF and TAPSE medians within the normal ranges (55% [55, 62] and 21 mm [18, 24], respectively). The LV and RV were significantly dilated (moderate or more) in 3.6% and 34% of patients, respectively. The median TR Vmax was just above the cutoff for pulmonary hypertension (2.91 m/s [2.2, 3.1]) (Table  1 ).

We investigated whether the PaO 2 /FiO 2 ratio, a marker of pneumonitis severity, correlated with TAPSE as an indicator of RV systolic function, the study’s primary endpoint. The PaO 2 /FiO 2 ratio was significantly and negatively correlated, albeit weakly, with TAPSE in this cohort (r 2  = 0.041, p  = 0.04); (TAPSE increased as PaO 2 /FiO 2 worsened) (Table  2 ; Fig.  2 A). There were no statistically significant correlations between PaO 2 , FiO 2 , PaCO 2 , pH, respiratory rate, mechanical ventilation, and TAPSE in this cohort (Table  2 ), the study’s secondary endpoint.

To further explore the association between the PaO 2 /FiO 2 ratio and TAPSE, we categorised the patients based on a TAPSE of 17 mm (lower limit of normal). Patients with TAPSE ≥ 17 mm ( n  = 93) had a significantly lower (worse) PaO 2 /FiO 2 ratio compared to those ( n  = 15) with TAPSE below 17 mm (18.6 [14.2, 31.2] vs. 32.1 [24.2, 43.2], p  = 0.005) (Fig.  2 B). Furthermore, univariate logistic regression revealed that the PaO 2 /FiO 2 ratio could predict TAPSE equal to or above or below the lowest normal cutoff (17 mm), with an OR (CI) of 0.94 (0.91, 0.98) and a p-value of 0.004. ROC analysis of this model demonstrated that the PaO 2 /FiO 2 ratio had a good AUC (0.72, p  = 0.006) for predicting TAPSE (Fig.  2 C). Moreover, a PaO 2 /FiO 2 ratio of 26.7 could predict TAPSE equal to or above or below 17 mm with reasonable sensitivity (67%) and specificity (68%).

Correlation between the PaO 2 /FiO 2 ratio and TAPSE in patients admitted to critical care with COVID-19 pneumonitis. A: Correlation between TAPSE and PaO 2 /FiO 2 . B: Comparison of the PaO2/FiO2 ratio medians between patients categorised based on TAPSE of 17 mm. C: ROC of the PaO 2 /FiO 2 ratio prediction of TAPSE equal to or above or below 17 mm. AUC: area under the curve. ROC: receiver operator curve. TAPSE: Tricuspid annular plane systolic excursion. **: p  < 0.01

To further explore the correlation between TAPSE and PaO 2 /FiO 2 , we performed a subgroup analysis of two distinct patient populations: those supported by mechanical ventilation ( n  = 63) and those supported by CPAP ( n  = 45). The analysis revealed that in patients supported by mechanical ventilation, TAPSE was significantly correlated with the PaO 2 /FiO 2 ratio (r 2  = 0.09, p  = 0.02). In contrast, in patients supported by facemask CPAP, the correlation was not statistically significant (r 2  = 0.01, p  = 0.46).

We conducted a retrospective study in a single centre to investigate the association between RV systolic function, indicated by the TAPSE, and the PaO 2 /FiO 2 ratio as a marker of disease severity in patients with COVID-19 pneumonitis who required respiratory support in critical care. Initially, we hypothesised that TAPSE would decrease as the PaO 2 /FiO 2 ratio worsened. However, our observations showed a weak but statistically significant association where TAPSE increased as the disease severity worsened early in the disease course, particularly in mechanically ventilated patients. This association was observed at a median of 3 days following admission to critical care. We observed no significant correlation between TAPSE and other respiratory parameters. Furthermore, patients with TAPSE levels equal to or above the lower limit of normal (17 mm) had significantly lower PaO 2 /FiO 2 ratios (worse) than those above this cutoff. We also discovered that the PaO 2 /FiO 2 ratio could predict whether TAPSE levels were equal to or above, or below the cutoff, with a good AUC of 0.72. Finally, we observed that the PaO 2 /FiO 2 ratio at the higher end of moderate ARDS (26.7) had reasonable sensitivity and specificity for predicting TAPSE.

TAPSE is a commonly used echocardiographic surrogate of RV systolic function. This biomarker represents tricuspid annulus longitudinal displacement towards the apex and is easily measured by M-mode echocardiography at the bedside. This cohort’s median TAPSE (21 mm) lies above the lower limit of the normal range (17 mm) and within the previously reported ranges in COVID-19 patients [ 9 , 10 , 11 ]. In a meta-analysis of COVID-19 patients, TAPSE was independently associated with mortality [ 9 , 12 ]. Where non-survivors exhibited lower TAPSE than survivors, each 1 mm decrease in TAPSE was associated with a further increase in mortality. In addition, COVID-19 patients with a lower TAPSE (19 mm vs. 21 mm) exhibited a significantly higher incidence of subsequent respiratory deterioration [ 13 ]. Furthermore, one study demonstrated a correlation between COVID-19 severity diagnosed using computed tomography (CT) and RV systolic function, in which a worse CT score was associated with lower TAPSE [ 14 ]. Based on these studies, we hypothesised that TAPSE deteriorates as the disease severity worsens. However, in the current cohort, TAPSE was negatively associated with the PaO 2 /FiO 2 ratio, where TAPSE increased as PaO 2 /FiO 2 worsened. Including all COVID-19 patients in critical care, rather than just those with hemodynamic instability who underwent echocardiography, as in previous studies, may explain the discrepancy between the findings of the current research and those of previous studies.

In the current study, earlier in the disease course, at a median of 3 days following admission to critical care, TAPSE increased against worsening COVID-19 pneumonitis. In a previous study, echocardiography was conducted within 24 h of admission to critical care for patients with COVID-19 pneumonitis [ 15 ]. The TAPSE values in that study were comparable to those found in the current study, and no significant differences were observed between survivors and non-survivors. Later, in the course of non-COVID-19 ARDS (within two weeks of onset), a study demonstrated that TAPSE correlated positively with the PaO 2 /FiO 2 ratio [ 16 ]. This was reflected in another cohort of COVID-19 patients; TTEs were conducted at a later stage of the illness, at a mean of six days after critical care admission, to assess hemodynamic compromise [ 17 ]. As the PaO 2 /FiO 2 ratio deteriorated, the fractional area change (FAC), another marker of RV systolic function, also worsened. Moreover, in another small study, all patients with COVID-19 pneumonitis underwent serial echocardiography in the intensive care unit [ 18 ]. This study’s mean initial TAPSE was comparable to the current study and was similar between survivors and non-survivors (22 mm vs. 21 mm, respectively). However, in the final scan, the TAPSE of survivors was maintained at 23 mm, while that of non-survivors dropped to 19 mm (a statistically significant drop). These results indicate that RV contractility initially increases in the face of worsening ARDS to enhance pulmonary blood flow, improve gas exchange, and overcome the pulmonary vascular dysfunction associated with ARDS [ 19 ]. However, the RV is exhausted in some patients, leading to a lower TAPSE and higher mortality risk in COVID-19. Therefore, when interpreting TAPSE, it is essential to consider the timing of echocardiography in relation to ARDS. A high TAPSE reading early in the disease course may indicate a high RV effort or a hyperdynamic RV, leading to later exhaustion and hemodynamic compromise in some patients.

The guidelines state that a TAPSE measurement of less than 17 mm indicates impaired RV systolic function [ 20 ]. However, this cutoff was developed based on studies of outpatient populations who are stable and not unwell, and their cardiovascular loading conditions differ significantly from those of critical care patients. Due to critical illness, sedation, invasive ventilation, changes in preload, and the effects of vasoactive medications, our patients’ loading conditions were different from those of outpatient populations. Critical care echocardiography practice adopts this cutoff to define abnormal RV function, but it may not be relevant to critical care situations. In critical illness situations where the RV does not need to work hard, TAPSE may fall below the guidelines cutoff without indicating an impairment or abnormality. This variation is also observed in some healthy athletes whose LV ejection falls below the abnormality limit set by the guidelines for the general population while their function remains normal [ 21 ]. The guidelines’ recommended normality ranges may not always apply to critical illness. This highlights the need for further research to improve our understanding of cardiac function and its response to changes in loading conditions over time. Further exploration of increased RV function or hyperdynamic RV may be necessary in the context of critical illness and ARDS.

This study has some limitations that may affect its generalisability. This was a single-centre retrospective study. Other RV parameters were not measured, such as right ventricular tissue Doppler systolic prime velocity, right ventricular outflow tract Doppler, and RV strain by speckle tracking. Some of these limitations may be explained by the impact of the COVID-19 pandemic on ICU staff workload and their ability to collect and record data. In addition, the British Society of Echocardiography advised the adoption of focused echocardiograms during the pandemic, which may have affected echocardiographic data. Furthermore, fewer patients had TAPSE measurements below the cutoff of 17 mm, which could introduce bias. Moreover, further bias may originate from excluding patients where TAPSE was not or could not be measured.

Our study revealed a weak but statistically significant negative correlation between RV systolic function, measured by TAPSE, and the severity of COVID-19 pneumonitis, expressed as the PaO 2 /FiO 2 ratio in the early stages of the disease. We observed that, as the PaO 2 /FiO 2 ratio worsened, there was an increase in TAPSE, more so in the mechanically ventilated. This finding could alert clinicians to the possibility of RV exhaustion in patients with worsening ARDS, even if TAPSE is normal in the early phase of the disease. Therefore, RV protection measures should be considered before hemodynamic changes occur. This study also opens the door to researching the RV response to ARDS over time, and further research is required to determine how TAPSE, and other RV function parameters respond to ARDS as it progresses. Moreover, critical care-specific guidelines for measuring RV function require further investigation.

In this retrospective study conducted in a single centre, we observed a weak but statistically significant negative association where RV systolic function indicated by TAPSE increased as the PaO 2 /FiO 2 ratio, a surrogate for disease severity, worsened in patients admitted to critical care with COVID-19 pneumonitis, particularly in patients who required mechanical ventilation. Patients with TAPSE levels equal to or above the lower limit of normal (17 mm) had significantly worse PaO 2 /FiO 2 ratios than those below the guidelines’ cutoff. We also discovered that the PaO 2 /FiO 2 ratio could predict whether TAPSE levels were equal to or above, or below the cutoff (17 mm), with a good AUC of 0.72. Finally, we observed that the PaO 2 /FiO 2 ratio at the higher end of moderate ARDS (26.7) had reasonable sensitivity and specificity for predicting TAPSE. These observations indicate that the TAPSE above the normal cutoff is not necessarily reassuring in the context of ARDS and may assist clinicians in managing the RV in this cohort. Further research is required to corroborate these observations in a prospective cohort and study RV changes in correlation with disease severity over time.

The Authors declare that there is no conflict of interest.

Data availability

Data is available from the corresponding author upon reasonable request.

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Lashin, H., Aron, J., Lee, S. et al. Correlation between worsening pneumonitis and right ventricular systolic function in critically ill patients with COVID-19. Echo Res Pract 11 , 19 (2024). https://doi.org/10.1186/s44156-024-00054-z

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Robinder g. khemani.

1 Pediatric ICU, Department of Anesthesiology and Critical Care Medicine, Children’s Hospital Los Angeles, Los Angeles, California

2 Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California

Jessica T. Lee

3 Division of Pulmonary, Allergy and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

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5 Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, New York

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Gökhan M. Mutlu

Hayley b. gershengorn.

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Rémi Coudroy

11 Institut National de la Santé et de la Recherche Médicale, Poitiers, France; and

12 Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Poitiers, Poitiers, France

In this review, we highlight the major scientific output in 2020 related to critical care in American Thoracic Society journals. Scientific focus surrounded acute respiratory distress syndrome (ARDS), sepsis, acute kidney injury (AKI), ICU organization, post-ICU recovery, critical care research, and education. This review focuses predominantly on original research articles and related commentary, but there were also several excellent review articles ( 1 – 3 ) and letters to the editor ( 4 – 12 ) related to critical care. Furthermore, there is a dedicated update on coronavirus disease (COVID-19), which also contains pertinent information related to critical care.

ARDS Pathogenesis

The identification of subphenotypes of ARDS has led to a more nuanced approach to clinical trials, but biomarkers to identify subphenotypes are often not available for clinical use. In a secondary analysis of the NHLBI ARDS Network clinical trials, a machine learning technique called “gradient-boosted machines” using routinely available clinical laboratory parameters reliably reidentified hyperinflammatory and hypoinflammatory subphenotypes initially identified using the latent classifier approach ( 13 , 14 ). Genetic predisposition to ARDS may be an important factor for future clinical trials. In a Mendelian randomization study on two well-phenotyped cohorts of critically ill patients with sepsis and ARDS, plasma sRAGE was genetically determined and identified as a potential causal factor in sepsis-associated ARDS ( 15 ). Logical next steps would include studying patients at risk for ARDS ( 16 ).

The renin–angiotensin system (RAS) has been implicated in the pathogenesis of ARDS. A normal angiotensin I–to–angiotensin II ratio was inverted in individuals with early ARDS but not in surgical control subjects, and it was associated with poor outcomes in patients with ARDS ( 17 ). In addition, biomarkers of the alternative RAS pathway stimulated by neprilysin, Ang 1–7, and Ang 1–5 were higher in patients with ARDS than in control subjects, and RAS dysregulation was noted to persist in later ARDS.

Lung repair after ARDS continued to be a focus in preclinical studies. Regulatory T cells (Tregs) are elevated in human blood and BAL fluid from patients with ARDS; however, the mechanism by which Tregs alter alveolar type II IFN responses remains unclear. Using gene ontology analysis in an animal model of ARDS, gene sets composing type I IFN, intracellular transport, and cellular localization were upregulated in the Treg-depleted samples ( 18 ). Tregs may be a potential therapeutic target in the resolution phase of ARDS ( 19 ). Permissive hypercapnia may have unintended consequences for cellular metabolism and may slow down wound healing in epithelial monolayers through the inhibition of Rac1/Cofilin via AMPK ( 20 ). Upregulation of NF-κB suppressed CXCL12 and activated Rac1 via the binding to CXCR4 and prevented the adverse effects of hypercapnia in an orthotopic tracheal transplantation model of wound healing ( 20 ).

Lung-Protective Ventilation and Ventilator-induced Lung Injury

Positive end-expiratory pressure (PEEP) management in ARDS remains controversial, with a heterogenous response being based on lung recruitability. Through a physiologic study in 45 adults with ARDS, a single-breath method to assess recruitability by calculating the recruitment-to-inflation ratio provided a simple way to identify patients who may benefit from a higher-PEEP strategy ( 21 , 22 ). The addition of expiratory resistance in both spontaneously breathing and mechanically ventilated pigs with lung injury resulted in less heterogeneous expiratory time constants, preventing end-expiratory lung collapse. The method may provide an alternative or adjuvant approach to PEEP management to prevent atelectrauma and regional overdistention in heterogenous lung disease ( 23 , 24 ).

A pilot study demonstrated that a strategy to limit driving pressure in adult patients with ARDS, compared with conventional low V t ventilation, was feasible ( 25 ). Although providing a foundation for future trials, deep sedation or paralysis was required and may limit its widespread use ( 26 ). Mechanistically, stretch-related ventilator-induced lung injury may be decreased by the activation of Piezo1, a nonselective cation channel that allows the influx of calcium and sodium into endothelial cells, stabilizes endothelial adherens junctions and lung vascular barriers ( 27 ), and activates calpain ( 28 ).

Patient Self-inflicted Lung Injury and Ventilator-induced Diaphragm Dysfunction

Although ventilator-induced lung injury has been well recognized over the last several decades, it is becoming increasingly clear that lung injury can occur when patients have a strong respiratory drive, a term collectively known as patient self-inflicted lung injury (P-SILI). P-SILI is exacerbated when patients achieve high V t s with correspondingly high transpulmonary pressure, particularly when lung compliance is impaired. Strategies have been developed to identify patients with significant respiratory effort who are at high risk of P-SILI, both on invasive and noninvasive mechanical ventilation. It is also important to identify mechanically ventilated patients with very low respiratory effort, as this is a risk factor for ventilator-induced diaphragm dysfunction.

Through secondary analysis of 132 mechanically ventilated patients with moderate-to-severe ARDS, neuromuscular blockade was only beneficial in the subgroup with higher baseline diaphragm thickness and was harmful in the subgroup with lower baseline diaphragm thickness, suggesting that patients with higher baseline thickness may have the strength to generate more injurious transpulmonary pressures and are at higher risk of P-SILI ( 29 ).

Airway occlusion maneuvers during expiration or inspiration can be used to estimate patient effort or driving pressure. As compared with esophageal pressure, excessively high or low respiratory effort can be reliably detected using the ventilator-calculated change in pressure during the first 100 ms of a breath during airway occlusion ( 30 , 31 ). During assisted ventilation on pressure support, driving pressure measured during inspiratory or expiratory airway occlusion maneuvers are highly correlated with one another. Specifically, the negative deflection in airway pressure during an expiratory hold multiplied by 0.75 plus the set pressure support level represents the dynamic driving pressure. This dynamic driving pressure was found to be nearly identical to the static driving pressure measured as the difference between the plateau pressure during an inspiratory hold and the PEEP level, after controlling for the airway resistance.

Tissue doppler imaging of the diaphragm using ultrasound is a novel technique to monitor respiratory effort and identify patients likely to experience weaning failure. The technique was highly reproducible and identified differences between patients with weaning failure and patients with weaning success or healthy volunteers, and parameters were correlated with gold standard measures of respiratory effort, such as the transdiaphragmatic pressure time product ( 33 , 34 ). Electrical activity of the diaphragm, often used to measure patient effort and gauge patient–ventilator synchrony, may have limitations in detecting ineffective respiratory effort, as compared with esophageal manometry or surface electromyography ( 35 ).

In patients with hypoxemic respiratory failure treated with noninvasive ventilation (NIV), strong spontaneous breathing effort (large swings in esophageal pressure) were associated with worsening of lung injury on chest radiographs and an increased risk of intubation. Minimal reduction in esophageal pressure swings (<10 cm H 2 O) after 2 hours of NIV was more strongly associated with intubation than large expiratory V t s; the Heart Rate, Acidosis, Consciousness, Oxygenation, and Respiratory Rate score; or other physiologic parameters ( 36 , 37 ). Higher pressure support was strongly associated with decreasing spontaneous breathing effort ( 38 ).

In a physiologic crossover study on 15 patients with acute hypoxemic respiratory failure, use of high-PEEP helmet NIV was associated with improved oxygenation and work of breathing compared with use of a high-flow nasal canula (HFNC). Patients with high inspiratory effort during HFNC use were more likely to have improvement with helmet NIV use, but patients with low inspiratory effort during HFNC use had increased transpulmonary pressure swings during helmet NIV use, which may have resulted in larger and harmful V t s ( 39 , 40 ). Although V t is generally not measurable during helmet NIV use, it may be accurately measured by using a turbine-driven ventilator connected to the inspiratory port of the helmet by using a single-limb circuit with an intentional calibrated leak from the expiratory port of the helmet ( 41 ).

Adjuvant ARDS Therapies and Extracorporeal Membrane Oxygenation

Mesenchymal stem cells have been a recent focus in ARDS. The 1-year and 5-year follow-up results of two patients who had received a single intravenous infusion of allogenic bone marrow–derived mesenchymal stromal cells were reported and showed full resolution of lung parenchymal injuries on computed tomography scans ( 42 ). In an animal model of ARDS treated with extracorporeal membrane oxygenation (ECMO), endobronchial infusion of induced pluripotent stem cell–derived human mesenchymal stem cells was associated with decreased lung inflammation, histologic lung injury, and shock severity. However, no differences in oxygenation or respiratory mechanics were observed, and stem cells were associated with pulmonary arterial thromboses and impairment of the membrane oxygenator ( 43 , 44 ).

Adjuvant therapies for ARDS are used with significant variability among institutions. An observational study conducted in 100 international pediatric ICUs identified that continuous neuromuscular blockade was used in 30% of patients with pediatric ARDS and in 50% of patients with severe pediatric ARDS, whereas the remainder of other adjuvant therapies were used less than 15% of the time. There were significant regional and institutional differences in the application of adjuvant therapies and their order of implementation ( 45 , 46 ). Some of these institutional differences may relate to comfort with the therapy and training, particularly for prone positioning. According to a survey conducted in 54 acute care hospitals in Massachusetts, only 44% of hospitals were “prone ready,” and the absence of a protocol for prone positioning was associated with the use of other therapies ( 47 ).

Data from the Extracorporeal Life Support Organization registry suggested that a relative drop in Pa CO 2 > 50% in the first 24 hours of ECMO was associated with a 70% increased risk of neurologic complications. These findings suggest that Pa CO 2 or the related cerebral vasoconstriction should be monitored after ECMO initiation to guide sweep gas flow ( 48 , 49 ). Interestingly, Bourcier and colleagues ( 50 ) reported favorable outcomes in four out of five young patients with refractory obstructive shock secondary to mediastinal compressive tumors with ECMO and chemotherapy.

Translational and Preclinical Studies on the Lung

Electronic cigarette– or vaping-associated lung injury is a recently recognized cause of ARDS in young individuals. Vitamin E acetate caused dose-dependent increases in pulmonary edema as well as organizing and lipoid pneumonia in a mouse model of electronic cigarette– or vaping-associated lung injury through the upregulation of the gene expression of inflammatory pathways and through a direct toxic effect on alveolar type II cells ( 51 ). α-Tocopherol, a metabolite of Vitamin E acetate is a free radical scavenger that has been proposed to treat ARDS. Pretreatment of endothelial and epithelial cells with α-tocopherol reduced paracellular permeability induced by Pseudomonas aeruginosa exoenzyme (type III secretion system) and prevented mortality in a mouse model of P. aeruginosa pneumonia ( 52 ).

Severe meconium aspiration syndrome (MAS) is a neonatal form of ARDS. A translational study using nonbronchoscopic BAL fluid from neonates with MAS compared with that of control subjects found that MAS was associated with significant changes in the surfactant phospholipid profile, with an increase in lysophosphatidylcholine and surfactant proteins B and C being shown. In addition, MAS was also associated with alteration of surfactants’ nanostructure, possibly due to concurrent lung inflammation ( 53 ).

Viral and bacterial products activate the innate immune system through TLR (Toll-like receptor) signaling. TLR8 protein levels were lower in blood samples of patients with ARDS compared with blood samples of healthy control subjects. The authors discovered that E3 ligase RNF216 (ring finger protein 216) ubiquitinates TLR8 in response to microRNAs. Gene expression profiles obtained from patients with ARDS had reduced RNF216. Furthermore, RNA extracted from plasma of human ARDS samples activated TLR8 in a macrophage cell line in vitro , suggesting that TLR8–RNF216 signaling plays an important role in ARDS ( 54 ) and that the hyperinflammatory phenotype is perhaps due to reduced RNF216 ( 55 ). The time course of immune system activation is critical in the development of ARDS. Harnessing epithelial antiviral properties has the potential to decrease the pulmonary viral burden and hence the occurrence of ARDS. Inhaled Pam2-ODN, a TLR 2/6 and 9 agonist, reduced the lung Sendai virus (the murine form of the human parainfluenza virus) burden and decreased mortality in mice. In addition, Pam2-ODN blocked the increase in CD8 + T cells induced by viral challenge, leading to reduced mortality ( 56 ). However, the mechanism for viral inactivation due to Pam2-ODN and its effects on established viral pneumonia are unknown ( 57 ).

Respiratory viral infections are common in children and can be associated with poor outcomes. In neonates with respiratory syncytial virus, higher disease severity was related to CD8 + T cells expressing IL-4 (Tc2) and reduced proportions of CD8 + T cells expressing IFNg (Tc1) in nasal aspirates. Less severe disease was associated with greater frequencies of Tc1, CD8 + T cells expressing IL-17 (Tc17), and CD4 + T cells expressing IL-17 (Th17), highlighting the importance of T-cell subsets in the pathogenesis and severity of respiratory syncytial viral infection ( 58 ). The nasal washing cytokine composition of pediatric allogeneic hematopoietic cell-transplant patients in the absence of viral respiratory tract infection is different from that of healthy control subjects and produced higher concentrations of IL-4, IL-12p40, and IL-1ra during a viral infection ( 59 ).

The lung microbiome was a focus of several investigations. Using droplet digital PCR and bacterial 16S quantification and sequencing in mini-BAL fluid before the receipt of antibiotics, differences in the lung microbiome were predictive of ventilator-free days and were associated with the diagnosis of ARDS ( 60 ). Enterobacteriaceae predominance was a risk factor for poor outcomes ( 61 ). Similarly, three clusters of endotracheal aspirate flora and two clusters of oral flora were identified in ICU patients with respiratory failure before administration of antibiotics. Individual clusters were associated with bacterial diversity, the prevalence of pathogenic bacteria, inflammation, and outcomes ( 62 ). Together, these findings suggest that the alteration of the airway microbiome of ICU patients may be a modifiable factor or therapeutic target ( 63 ).

The incidence of bronchopulmonary dysplasia is increasing. Maternal vitamin D deficiency impaired lung development in rats, causing outcomes including a simplified distal lung structure and higher resistance and airway hyperactivity in experimental animals compared with control animals ( 64 ). These changes mimicked those seen after postnasal hyperoxia exposure and may be explained by an abnormal reduction of HIF-1α/VEGF signaling ( 64 , 65 ). Basal autophagy is impaired during neonatal hyperoxia-induced lung injury and in a baboon model of bronchopulmonary dysplasia. Autophagy-deficient mice had reduced alveolarization, increased expression of proinflammatory genes, and enhanced NLRP3 inflammasome activation in alveolar macrophages, increasing their susceptibility for neonatal hyperoxia-induced lung injury ( 66 ).

Other Studies of Mechanical Ventilation

Ciliary dyskinesia was common in mechanically ventilated patients suspected of having pneumonia and was associated with the severity of respiratory failure but not with ventilator-associated events or outcomes ( 67 ). The prevalence of probable Aspergillus infection using the algorithm proposed by the AspICU investigators ( 68 ) was as high as 12% in patients without neutropenia who had suspected ventilator-associated pneumonia and was associated with longer ICU stays but was not associated with higher mortality ( 69 , 70 ). In contrast, invasive tracheobronchial aspergillosis, as suggested by the presence of endotracheobronchial lesions in patients with Aspergillus infection, was diagnosed in 29% of patients with severe influenza and pulmonary aspergillosis, and their in-ICU mortality rate was 90% despite antifungal treatment ( 71 , 72 ).

From 2010 to 2017, NIV was used as the first-line treatment of asthma exacerbation in 25% of cases and increased over time. Although it failed in 22% of cases, use of NIV was independently associated with lower risks of intubation and mortality ( 73 , 74 ). On the basis of administrative diagnosis data of ICU admissions in Australia and New Zealand, it was shown that the percentage of ICU admissions with acute exacerbations of chronic obstructive pulmonary disease increased between 2005 and 2017 but that mortality decreased ( 75 , 76 ).

Among patients with respiratory failure requiring mechanical ventilation in Taiwan, more than 90% of successful weaning outcomes occurred in the first 30 days of mechanical ventilation, and the probability of death surpassed that of weaning after the 27th ventilator day ( 77 ). It remains to be seen whether the online prognosis tool derived from this study informs shared decision-making and whether these results are generalizable ( 78 ). The characteristics of high-performing centers specialized in the management of patients with prolonged mechanical ventilation included hospital leadership engagement in quality improvement, adequate staffing, detailed yet flexible protocols to increase the autonomy of bedside providers, and interdisciplinary team meetings. Key factors associated with effective care included the coordination among caregivers to balance aggressiveness and responsiveness and the involvement of patients and their families in decision-making ( 79 , 80 ).

Delirium is common among ICU patients, particularly among those on mechanical ventilation. In a secondary analysis of two randomized controlled trials on delirium management, five trajectories of delirium, integrating symptom severity and duration, were identified as being associated with patient characteristics and 30-day mortality ( 81 ).

In ventilated patients, the optimal nutritional target remains as a subject of debate because delivery of 100% or 70% of the recommended calorie intake in the acute phase of critical illness did not result in significant differences in the long-term mortality, disability, quality of life, or return-to-work rate of survivors after 6 months ( 82 , 83 ).

Clinical Studies in Sepsis

Hydrocortisone, high-dose ascorbic acid, and thiamine therapy has been considered in septic shock ( 84 ). From 2015 to 2018, its use in adults admitted to the ICU for septic shock increased from use in 0.03% of patients to use in over 2.5% of patients. There was marked heterogeneity in its use among centers, with use in up to 20% of patients in some hospitals, especially in patients with more severe organ dysfunction. In a retrospective cohort analysis in adults, its use was associated with worse outcomes despite extensive multivariable modeling and propensity matching ( 85 ). In contrast, in a single-institution pediatric study, hydrocortisone, high-dose ascrobic acid, and thiamine therapy were associated with improved clinical outcomes when compared to control therapy after propensity score-matched and inverse probability-weighted analyses ( 86 ). Differences in patient selection, criteria for allocation of treatment, and unmeasured confounding likely contribute to the seemingly conflicting results of these two studies. Interestingly, baseline levels of cortisol, aldosterone, or ascorbic acid were not related to the treatment effect of hydrocortisone on mortality, shock resolution, or other clinical outcomes in a secondary analysis of the Adjunctive Corticosteroid Treatment in Critically Ill Patients With Septic Shock (ADRENAL) trial, a large, multinational, randomized, placebo-controlled trial of stress steroids in septic shock ( 87 , 88 ).

In a secondary analysis of the randomized controlled trial of exogenous angiotensin II in vasodilatory shock (ATHOS-3) ( 89 ), the response to treatment was heterogeneous. Higher renin levels were associated with kidney injury and with a higher angiotensin I/II ratio ( 90 ). Compared with placebo treatment, treatment with exogenous angiotensin II improved outcomes in the subgroup of patients with higher renin levels ( 91 ).

Through a Bayesian reanalysis of the randomized clinical trial comparing peripheral perfusion to a lactate-clearance resuscitation strategy (ANDROMEDA-SHOCK), there was a >90% likelihood that the peripheral perfusion strategy was better, using a wide range of assumptions about the prior probability. Bayesian networks were also used to analyze patterns of change in Sequential Organ Failure Assessment (SOFA) scores, with death as a competing risk ( 92 , 93 ).

Premorbid (baseline) blood pressure influenced the duration of vasopressor medication use in the ICU ( 94 ). Compared with normal premorbid blood pressure, a lower premorbid blood pressure was associated with a longer duration of vasopressor use and higher mortality, whereas higher premorbid blood pressure was associated with a shorter duration of vasopressor use, suggesting that differential blood pressure targets stratified by premorbid blood pressure should be evaluated ( 95 ). In addition, the depth and duration of the blood pressure deficit during critical illness compared with a premorbid measurement was associated with risk of a major adverse kidney event ( 96 , 97 ).

Methods to improve delivery of care to patients with sepsis was a focus. Compliance with a 3-hour sepsis treatment bundle varied between daytime and nighttime and between emergency and nonemergency areas, suggesting the need to incorporate the setting of diagnosis into quality-improvement initiatives ( 98 ). In a pilot trial, coated devices (endotracheal tubes, central venous catheters, and urinary catheters) were found to be possibly associated with more days alive and free of antibiotics ( 99 ). The provision of palliative care consultation for older patients who died with a diagnosis of septic shock was associated with shorter lengths of stay and lower hospital costs compared with no provision of palliative care ( 100 ). Sepsis-associated mortality rates improved in patients with cancer but not in patients without cancer ( 101 ), highlighting the need to understand the interplay between cancer and sepsis and the validity of administrative data surrounding cancer and sepsis ( 101 , 102 ). In selected patients labeled as being allergic to penicillin who had a history of low-risk clinical manifestations, direct oral amoxicillin challenge without prior desensitization or skin testing was shown to be safe and allowed for the removal of inaccurate penicillin allergy labels ( 103 ).

Diagnostic tools in sepsis may need modification to achieve optimal performance in resource-limited settings. In a prospective study on patients with suspected infection in Brazil, a quick SOFA (qSOFA) score ≥1 predicted mortality with a sensitivity of 84.9% (vs. 53.9% for a qSOFA score ≥2). In resource-limited settings, using a SOFA score ≥1 or using a qSOFA score ≥1 plus the lactate status to identify any organ dysfunction could be alternatives to the usual method of identification using a qSOFA score ≥2 ( 104 , 105 ). In patients with sepsis hospitalized in Malawi, sonographic lung B-lines indicating supleural interstitial edema were strongly associated with eventual hypoxemia (area under the curve, 0.86 [95% confidence interval, 0.69–0.97]), with a dose–response increase in the number of B-lines and a dose–response decrease in oxygen saturation occurring with each liter of intravenous crystalloid administered ( 106 ).

Translational Studies in Sepsis

Compared with placebo and vasopressin administration, norepinephrine administration increased IL-10 levels in human leukocytes, increased bacterial growth after cecal ligation in a mouse model, and altered the cytokine response to an LPS challenge in healthy patients ( 107 ). However, the immune balance of patients admitted with sepsis remains incompletely understood, and large randomized trials have not demonstrated increased harm with norepinephrine administration ( 108 ).

In a proof-of-concept study in pediatric patients with sepsis, a microfluidic multianalyte system had acceptable agreement with biomarkers measured with standard ELISA techniques, which were associated with mortality. This may facilitate nearly real-time assessment of biomarker profiles for precision medicine approaches and trials ( 109 ).

Analysis of the differential RNA expression in the cortical gray matter of older patients with dementia who died of infectious versus noninfectious causes revealed clusters of gene transcripts that were associated with infection, including classical innate immune-related genes, damage-associated molecular patterns, complement factors, and cytokines ( 110 ). These results provide new targets for sepsis-associated brain injury research.

Higher levels of alternative complement pathway activity in the serum of critically ill patients were associated with higher levels of other complement-associated proteins, a hypoinflammatory phenotype, and better outcomes ( 111 ). Differential complement activation may represent differing host complement reserves or differential sampling ( 112 ).

Early identification of patients likely to develop AKI may have therapeutic implications. The development of severe kidney injury after ICU admission could be accurately identified through the measurement of admission serum creatinine and the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) biomarker panel within the first 24 hours of sepsis diagnosis. This may help identify patients who may benefit from renal protective interventions ( 113 , 114 ).

Patients with high serum proenkephalin (a renal biomarker) had a higher mortality rate than those without, but this mortality rate remained lower than that of those with overt AKI, suggesting that proenkephalin may help identify subclinical kidney injury ( 115 , 116 ). Through secondary analysis of a randomized clinical trial comparing resuscitation strategies for patients at risk of septic shock, the product of tissue inhibitor of metalloproteinases-2 and insulin-like growth factor–binding protein 7 in urine was associated with the up-front severity of illness and was predictive of Kidney Disease Improving Global Outcomes stage 3 kidney injury, renal replacement therapy, or death within 7 days ( 117 , 118 ). The genetic predisposition for developing AKI, associated with SNPs at the RF2 and TBX1 loci, was not confirmed in a large Finnish ICU population ( 119 ), tempering the enthusiasm for genome-wide association studies that do not have rigorous prior evidence for implicated pathways.

Using principles of the Stewart strong ion difference, an extracorporeal mechanism to remove blood chloride successfully decreased blood chloride, improved pH and urinary chloride and ammonium excretion, and was well tolerated in an animal model of respiratory and metabolic acidosis without shock ( 120 ). This may represent an alternative treatment for acidosis, although advantages over traditional dialysis are not clear ( 121 ).

ICU Organization

Nearly one in six ICU admissions are potentially preventable, with wide variation across U.S. states ( 122 ), suggesting that up-front investments in ambulatory care may enable the avoidance of ICU admissions and that preventable ICU admissions could serve as a metric of population health ( 123 ). Hospital strain, measured by a novel composite strain index, was strongly associated with ICU admission for patients with sepsis and/or acute respiratory failure, setting up a within-hospital variable to assess the marginal benefit of ICU admission ( 124 ). In Australia and New Zealand, ICU discharge delay for more than 6 hours occurred in 25% of patients and was associated with lower ICU readmission and hospital mortality, especially in the subgroup of patients with the highest predicted risk of mortality at ICU admission ( 125 , 126 ). Identifying factors associated with ICU readmission is important because clinicians had only fair accuracy in predicting it ( 127 ). This may reflect the complexity of ICU admission and/or readmission as an organizational construct ( 128 ).

The structure and makeup of the ICU may have important implications for patient outcomes. In a before and after cohort study, the rollout of an emergency department–embedded critical care unit was not associated with improved outcomes ( 129 ), which puts into question whether the potential benefits are offset by the incurred harm of such units ( 130 , 131 ). However, nurse staffing models and network relationships of nursing teams ( 132 ), as well as interactions between staff members (measured through the analysis of wearable badges) ( 133 ), seemed to play an important role in the outcomes of ICU patients. Furthermore, in rural hospitals, initiatives, attitudes, and ownership of change are key determinants for implementing evidence-based practice in the ICU, leading to better program engagement ( 134 ). In addition, methods to extend the influence of critical care physicians, including telemedicine approaches that enable physicians to participate as “copilots” guiding resuscitation during in-hospital cardiac arrest, may be beneficial on the wards of community hospitals ( 135 ).

Unfortunately, increasing demands on critical care practitioners may have consequences, as nearly 80% of division directors in pulmonary, sleep, and critical care believed that burnout was a problem in their division. Many drivers of burnout were inherent to personality characteristics of individuals or characteristics of the job, but many potentially modifiable factors, such as misalignment between the clinicians and administration, the electronic health records, and the workplace climate, were identified ( 136 ).

Disparities have a large impact on patient outcomes. Among critically ill patients, 25% of African American patients and 48% of Hispanic patients were concentrated in only 14 out of 208 U.S. hospitals. Hospital mortality and ICU and hospital stays decreased over time but remained higher in minority-serving hospitals than in non–minority-serving hospitals and did not change in the subgroup of African American patients ( 137 , 138 ). Another study identified that female survivors of shock or respiratory failure had poorer physical and psychological function than male survivors and were less likely to live at home 3 months after discharge, although most of these differences attenuated after 12 months ( 139 ).

Novel therapeutics have improved outcomes for many patients with cancer, although they may have adverse events prompting ICU admission. Patients who received chimeric antigen receptor T-cell therapy for lymphoma had higher rates of ICU admission for neurotoxicity and longer hospital stays than control patients with lymphoma, although ICU lengths of stay were shorter and the 60-day mortality was lower for these patients than for control patients with lymphoma admitted to the ICU ( 140 ).

Post-ICU Trajectories and Patient/Family Satisfaction

Critical illness survivors’ priorities evolved during recovery from basic survival concerns (e.g., mobility, participating in self-care) immediately after leaving the ICU to more aspirational concerns (e.g., seeking new experiences) 2 months after discharge ( 141 ). Identifying factors associated with post-ICU morbidity has therefore been a focus. In patients older than 65 years of age with severe traumatic brain injury, age and an Injury Severity Score ≥25 were independently associated with functional outcomes, with only 6% of patients recovering functional independence by 6 months ( 142 , 143 ). Furthermore, at the transition out of the hospital ( 144 ), adherence to expert recommendations in the postsepsis setting (medication optimization, screening for common impairments, monitoring for common preventable causes of deterioration, and treatment alignment with patient preferences) ( 145 ) occurred in only 11% of patients recovering from sepsis but was associated with an 88% reduced odds of death or hospital readmission ( 146 ). Although there is often a concern that opioid use in the ICU may lead to dependence after ICU discharge, persistent opioid use 1 year after hospital discharge was reported in only 2.6% of ICU survivors treated with mechanical ventilation ( 147 , 148 ).

Family satisfaction is a crucial component of delivering high-quality critical care, as illustrated by the need for a family-centered discharge approach focused on the coordination of care and teaching of emergency preparedness as keys to the safe discharge of tracheostomized children or young adults ( 149 ). These themes suggest opportunities to use simulation for education on airway emergencies and to use telemedicine for minimizing the risks of travel ( 150 ). During the second and third weeks of patients’ ventilation, both surrogate decision-makers and physicians were less likely to prefer that mechanical ventilation be continued for patients with poor prognoses, but surrogates required until Week 3 of mechanical ventilation before incorporating the prognosis into their decision-making ( 151 ). Interestingly, the concepts of futile or inappropriate treatment were difficult to understand for community members, but most were able to recognize inappropriate treatment when presented with a case ( 152 ). Inadequate physician–patient communication may underpin the difficulty with the concept, together with fears that the judgment of medical futility could undermine patient/family autonomy. Nevertheless, for patients who died in the hospital, complete ICU or mixed ICU/general-floor care at the end of life was consistently associated with higher family satisfaction, highlighting the importance of ICU care at the end of life ( 153 , 154 ).

Critical Care Research

Disparities are apparent in the gender breakdown of critical care authorship over the last 10 years. Only 30% of critical care publications have a female first author, with less than 20% having a female senior author, although the presence of a female senior author was associated with a higher likelihood of having a female co-author. This may be contributing to there being fewer women in leadership positions in critical care ( 155 , 156 ).

Improving methods to perform critical care research was a focus of several investigations. Many collaborative critical care research networks are focused on conducting high-quality randomized controlled trials but are highly dependent on external sources of funding to support network infrastructure ( 157 ). The creation of common protocols and approaches is crucial for the success of critical care trials. Recommendations on the maximal blood volume allowable for research and on the safe lower limit of Hb at the time of blood draws for critically ill patients have been proposed ( 158 ). Trial recruitment is often challenging in the ICU ( 159 ), and a collection of “nudges” presented to surrogate decision-makers as a preconsent survey was not an effective means of increasing enrollment in a sham trial ( 160 ). This prompts a need to better understand how surrogates perceive the risk of trial participation.

Administrative data are frequently used in critical care research investigations, and analyses using such data have more accurately identified the use of mechanical ventilation, but not the use of vasoactive medications or acute renal replacement therapy, than clinical chart review ( 161 ). Integration of electronic health record data may be required to answer some questions ( 162 ).

Education in Critical Care

This past year, the greatest accomplishment in critical care education was helping nonintensivists care for patients in the ICU. Educational content was rapidly created and widely disseminated through publications as well as on social media platforms such as Twitter, which had been widely used by intensivists before the pandemic and became an even more powerful tool for education during the pandemic ( 163 ). Much of the educational content aimed at helping care for patients with COVID-19 was published in ATS Scholar , a new open-access journal disseminating medical education focused on pulmonary, critical care, and sleep medicine. A series of videos ( 164 – 167 ) on mechanical ventilation for those with limited or nonexistent training proved to be an invaluable resource for clinicians redeployed to work in ICUs during the pandemic. In light of severely stretched staffing, the concept of “respiratory therapy extenders” was created, and a framework for how to train medical students as such extenders was reported ( 168 ). Online resources with quick tips and algorithms for nonintensivists to reference when caring for critically patients ( 169 , 170 ) as well as methods to keep intensivists up to date on the rapidly changing evidence related to the care of patients with COVID-19, such as the “Fast Literature Assessment and Review Initiative,” were shared widely ( 171 ).

Originally Published in Press as DOI: 10.1164/rccm.202102-0336UP on March 15, 2021

Author disclosures are available with the text of this article at www.atsjournals.org .