Practice and Predictors of Do-Not-Resuscitate Orders in a Tertiary-Care Intensive Care Unit in Saudi Arabia.

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.

Quality Indicators in Adult Critical Care Medicine.

Quality indicators are increasingly used in the intensive care unit (ICU) to compare and improve the quality of delivered healthcare. Numerous indicators have been developed and are related to multiple domains, most importantly patient safety, care timeliness and effectiveness, staff well-being, and patient/family-centered outcomes and satisfaction. In this review, we describe pertinent ICU quality indicators that are related to organizational structure (such as the availability of an intensivist 24/7 and the nurse-to-patient ratio), processes of care (such as ventilator care bundle), and outcomes (such as ICU-acquired infections and standardized mortality rate). We also present an example of a quality improvement project in an ICU indicating the steps taken to attain the desired changes in quality measures.

Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial.

BACKGROUND: The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. METHODS: In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8-1.2 g/kg/day). The primary outcome is 90-day all-cause mortality; other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30 to 25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data. CONCLUSION: Ethics approval was obtained from the institutional review board, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04475666 . Registered on July 17, 2020.

Comparison of the safety and efficacy for different regimens of pharmaco-prophylaxis among severely burned patients: a randomized controlled trial.

PURPOSE: Venous thromboembolism (VTE) is a common complication in critically ill patients, including severe burn cases. Burn patients respond differently to medications due to pharmacokinetic changes. This study aims to assess the feasibility and safety of different VTE pharmaco-prophylaxis in patients admitted to the ICU with severe burns. METHODS: A pilot, open-label randomized controlled trial was conducted on ICU patients with severe burns (BSA ≥ 20%). By using block randomization, patients were allocated to receive high-dose enoxaparin 30 mg q12hours (E30q12), standard-dose enoxaparin 40 mg q24hours (E40q24), or unfractionated heparin (UFH) 5000 Units q8hours. In this study, the primary outcomes assessed were the recruitment and consent rates, as well as bleeding or hematoma at both the donor and graft site. Additionally, secondary measures were evaluated to provide further insights. RESULTS: Twenty adult patients out of 114 screened were enrolled and received E30q12 (40%), E40q24 (30%), and UFH (30%). The recruitment rate was one patient per month with a 100% consent rate. Donor site bleeding occurred in one patient (16.7%) in the UFH group. On the other hand, graft site bleeding was only reported in one patient (12.5%) who received E30q12. Major bleeding happened in two patients, one in E30q12 and one in the UFH group. Five patients (25.0%) had minor bleeding; two patients (25.0%) received E30q12, two patients E40q24, and one patient UFH. RBC transfusion was needed in four patients, two on E30q12 and two on UFH. Only one patient had VTE, while four patients died in the hospital. CONCLUSION: The study observed a low recruitment rate but a high consent rate. Furthermore, there were no major safety concerns identified with any of the three pharmacologic prophylaxis regimens that were evaluated. TRIAL REGISTRATION NUMBER: NCT05237726.

The use of Tocilizumab in COVID-19 critically ill patients with renal impairment: a multicenter, cohort study.

Tocilizumab (TCZ) is recommended in patients with COVID-19 who require oxygen therapy or ventilatory support. Despite the wide use of TCZ, little is known about its safety and effectiveness in patients with COVID-19 and renal impairment. Therefore, this study evaluated the safety and effectiveness of TCZ in critically ill patients with COVID-19 and renal impairment. A multicenter retrospective cohort study included all adult COVID-19 patients with renal impairment (eGFR˂60 mL/min) admitted to the ICUs between March 2020 and July 2021. Patients were categorized into two groups based on TCZ use (Control vs. TCZ). The primary endpoint was the development of acute kidney injury (AKI) during ICU stay. We screened 1599 patients for eligibility; 394 patients were eligible, and 225 patients were included after PS matching (1:2 ratio); there were 75 TCZ-treated subjects and 150 controls. The rate of AKI was higher in the TCZ group compared with the control group (72.2% versus 57.4%; p = 0.03; OR: 1.83; 95% CI: 1.01, 3.34; p = 0.04). Additionally, the ICU length of stay was significantly longer in patients who received TCZ (17.5 days versus 12.5 days; p = 0.006, Beta coefficient: 0.30 days, 95% CI: 0.09, 0.50; p = 0.005). On the other hand, the 30-day and in-hospital mortality were lower in patients who received TCZ compared to the control group (HR: 0.45, 95% CI: 0.27, 0.73; p = 0.01 and HR: 0.63, 95% CI: 0.41, 0.96; p = 0.03, respectively). The use of TCZ in this population was associated with a statistically significantly higher rate of AKI while improving the overall survival on the other hand. Further research is needed to assess the risks and benefits of TCZ treatment in critically ill COVID-19 patients with renal impairment.

Replacing protein via enteral nutrition in a stepwise approach in critically ill patients: the REPLENISH randomized clinical trial protocol.

BACKGROUND: Protein intake is recommended in critically ill patients to mitigate the negative effects of critical illness-induced catabolism and muscle wasting. However, the optimal dose of enteral protein remains unknown. We hypothesize that supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition formula to achieve high amount of enteral protein (range 2-2.4 g/kg/day) given from ICU day 5 until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve moderate amount enteral protein (0.8-1.2 g/kg/day) would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. METHODS: The REPLENISH (Replacing Protein Via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial is an open-label, multicenter randomized clinical trial. Patients will be randomized to the supplemental protein group or the control group. Patients in both groups will receive the primary enteral formula as per the treating team, which includes a maximum protein 1.2 g/kg/day. The supplemental protein group will receive, in addition, supplemental protein at 1.2 g/kg/day starting the fifth ICU day. The control group will receive the primary formula without supplemental protein. The primary outcome is 90-day all-cause mortality. Other outcomes include functional and quality of life assessments at 90 days. The trial will enroll 2502 patients. DISCUSSION: The study has been initiated in September 2021. Interim analysis is planned at one third and two thirds of the target sample size. The study is expected to be completed by the end of 2025. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04475666 . Registered on July 17, 2020.

Enteral Nutrition Safety and Outcomes of Patients with COVID-19 on Continuous Infusion of Neuromuscular Blockers: A Retrospective Study.

Background: Intravenous infusions of neuromuscular blocking agents (NMBAs) and prone positioning are recommended for acute respiratory distress syndrome (ARDS) due to COVID-19. The safety of enteral nutrition (EN) during these treatments is unclear. This study assessed EN tolerance and safety during NMBA infusion in proned and nonproned patients with ARDS due to COVID-19. Methods: This retrospective study evaluated patients who were admitted to a tertiary-care ICU between March and December 2020, had ARDS due to COVID-19, and received NMBA infusion. We assessed their EN data, gastrointestinal events, and clinical outcomes. The primary outcome was gastrointestinal intolerance, defined as a gastric residual volume (GRV) ≥500 ml or 200-500 ml with vomiting. We compared proned and nonproned patients. Results: We studied 181 patients (mean age 61.2 ± 13.7 years, males 71.1%, and median body mass index 31.4 kg/m2). Most (63.5%) patients were proned, and 94.3% received EN in the first 48 hours of NMBA infusion at a median dose <10 kcal/kg/day. GRV was mostly below 100 ml. Gastrointestinal intolerance occurred in 6.1% of patients during NMBA infusion and 10.5% after NMBA discontinuation (similar rates in proned and nonproned patients). Patients who had gastrointestinal intolerance during NMBA infusion had a higher hospital mortality (90.9% versus 60.0%; p=0.05) and longer mechanical ventilation duration and ICU and hospital stays compared with those who did not. Conclusion: In COVID-19 patients on NMBA infusion for ARDS, EN was provided early at low doses for most patients, and gastrointestinal intolerance was uncommon in proned and nonproned patients, occurred at a higher rate after discontinuing NMBAs and was associated with worse outcomes. Our study suggests that EN was tolerated and safe in this patient population.

Occurrence, Risk Factors, and Outcomes of Pulmonary Barotrauma in Critically Ill COVID-19 Patients: A Retrospective Cohort Study.

Objective: Pulmonary barotrauma has been frequently observed in patients with COVID-19 who present with acute hypoxemic respiratory failure. This study evaluated the prevalence, risk factors, and outcomes of barotrauma in patients with COVID-19 requiring ICU admission. Methods: This retrospective cohort study included patients with confirmed COVID-19 who were admitted to an adult ICU between March and December 2020. We compared patients who had barotrauma with those who did not. A multivariable logistic regression analysis was performed to determine the predictors of barotrauma and hospital mortality. Results: Of 481 patients in the study cohort, 49 (10.2%, 95% confidence interval: 7.6-13.2%) developed barotrauma on a median of 4 days after ICU admission. Barotrauma manifested as pneumothorax (N = 21), pneumomediastinum (N = 25), and subcutaneous emphysema (N = 25) with frequent overlap. Chronic comorbidities and inflammatory markers were similar in both patient groups. Barotrauma occurred in 4/132 patients (3.0%) who received noninvasive ventilation without intubation, and in 43/280 patients (15.4%) who received invasive mechanical ventilation. Invasive mechanical ventilation was the only risk factor for barotrauma (odds ratio: 14.558, 95% confidence interval: 1.833-115.601). Patients with barotrauma had higher hospital mortality (69.4% versus 37.0%; p < 0.0001) and longer duration of mechanical ventilation and ICU stay. Barotrauma was an independent predictor of hospital mortality (odds ratio: 2.784, 95% confidence interval: 1.310-5.918). Conclusion: s. Barotrauma was common in critical COVID-19, with invasive mechanical ventilation being the most prominent risk factor. Barotrauma was associated with poorer clinical outcomes and was an independent predictor of hospital mortality.

Association of early mobility with the incidence of deep-vein thrombosis and mortality among critically ill patients: a post hoc analysis of PREVENT trial.

BACKGROUND: This study assessed the mobility levels among critically ill patients and the association of early mobility with incident proximal lower-limb deep-vein thrombosis and 90-day mortality. METHODS: This was a post hoc analysis of the multicenter PREVENT trial, which evaluated adjunctive intermittent pneumatic compression in critically ill patients receiving pharmacologic thromboprophylaxis with an expected ICU stay ≥ 72 h and found no effect on the primary outcome of incident proximal lower-limb deep-vein thrombosis. Mobility levels were documented daily up to day 28 in the ICU using a tool with an 8-point ordinal scale. We categorized patients according to mobility levels within the first 3 ICU days into three groups: early mobility level 4-7 (at least active standing), 1-3 (passive transfer from bed to chair or active sitting), and 0 (passive range of motion). We evaluated the association of early mobility and incident lower-limb deep-vein thrombosis and 90-day mortality by Cox proportional models adjusting for randomization and other co-variables. RESULTS: Of 1708 patients, only 85 (5.0%) had early mobility level 4-7 and 356 (20.8%) level 1-3, while 1267 (74.2%) had early mobility level 0. Patients with early mobility levels 4-7 and 1-3 had less illness severity, femoral central venous catheters, and organ support compared to patients with mobility level 0. Incident proximal lower-limb deep-vein thrombosis occurred in 1/85 (1.3%) patients in the early mobility 4-7 group, 7/348 (2.0%) patients in mobility 1-3 group, and 50/1230 (4.1%) patients in mobility 0 group. Compared with early mobility group 0, mobility groups 4-7 and 1-3 were not associated with differences in incident proximal lower-limb deep-vein thrombosis (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI] 0.16, 8.90; p = 0.87 and 0.91, 95% CI 0.39, 2.12; p = 0.83, respectively). However, early mobility groups 4-7 and 1-3 had lower 90-day mortality (aHR 0.47, 95% CI 0.22, 1.01; p = 0.052, and 0.43, 95% CI 0.30, 0.62; p < 0.0001, respectively). CONCLUSIONS: Only a small proportion of critically ill patients with an expected ICU stay ≥ 72 h were mobilized early. Early mobility was associated with reduced mortality, but not with different incidence of deep-vein thrombosis. This association does not establish causality, and randomized controlled trials are required to assess whether and to what extent this association is modifiable. TRIAL REGISTRATION: The PREVENT trial is registered at ClinicalTrials.gov, ID: NCT02040103 (registered on 3 November 2013) and Current controlled trials, ID: ISRCTN44653506 (registered on 30 October 2013).

Characteristics, Management, and Outcomes of Community-Acquired Pneumonia due to Respiratory Syncytial Virus: A Retrospective Study.

Background: Respiratory syncytial virus (RSV), a well-known cause of bronchiolitis in children, can cause community-acquired pneumonia (CAP) in adults, but this condition is not well studied. Hence, we described the characteristics and outcomes of patients hospitalized for CAP due to RSV. Methods: This was a retrospective study of patients admitted to a tertiary-care hospital between 2016 and 2019 with CAP due to RSV diagnosed by a respiratory multiplex PCR within 48 hours of admission. We compared patients who required ICU admission to those who did not. Results: Eighty adult patients were hospitalized with CAP due to RSV (median age 69.0 years, hypertension 65.0%, diabetes 58.8%, chronic respiratory disease 52.5%, and immunosuppression 17.5%); 19 (23.8%) patients required ICU admission. The median pneumonia severity index score was 120.5 (140.0 for ICU and 102.0 for non-ICU patients; p = 0.09). Bacterial coinfection was rare (10.0%). Patients who required ICU admission had more hypotension (systolic blood pressure < 90 mmHg) and a higher prevalence of bilateral infiltrates on chest X-ray (CXR) (89.5% versus 32.7%; p < 0.001). Systemic corticosteroids were used in 57.3% of patients (median initial dose was 40 mg of prednisone equivalent) with ICU patients receiving a higher dose compared to non-ICU patients (p = 0.02). Most (68.4%) ICU patients received mechanical ventilation (median duration of 4 days). The overall hospital mortality was 8.8% (higher for ICU patients: 31.6% versus 1.6%, p < 0.001). Conclusions: Most patients with CAP due to RSV were elderly and had significant comorbidities. ICU admission was required in almost one in four patients and was associated with higher mortality.

Long-term outcomes of patients with COVID-19 treated with helmet noninvasive ventilation or usual respiratory support: follow-up study of the Helmet-COVID randomized clinical trial.

PURPOSE: To evaluate whether helmet noninvasive ventilation compared to usual respiratory support reduces 180-day mortality and improves health-related quality of life (HRQoL) in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. METHODS: This is a pre-planned follow-up study of the Helmet-COVID trial. In this multicenter, randomized clinical trial, adults with acute hypoxemic respiratory failure (n = 320) due to coronavirus disease 2019 (COVID-19) were randomized to receive helmet noninvasive ventilation or usual respiratory support. The modified intention-to-treat population consisted of all enrolled patients except three who were lost at follow-up. The study outcomes were 180-day mortality, EuroQoL (EQ)-5D-5L index values, and EQ-visual analog scale (EQ-VAS). In the modified intention-to-treat analysis, non-survivors were assigned a value of 0 for EQ-5D-5L and EQ-VAS. RESULTS: Within 180 days, 63/159 patients (39.6%) died in the helmet noninvasive ventilation group compared to 65/158 patients (41.1%) in the usual respiratory support group (risk difference - 1.5% (95% confidence interval [CI] - 12.3, 9.3, p = 0.78). In the modified intention-to-treat analysis, patients in the helmet noninvasive ventilation and the usual respiratory support groups did not differ in EQ-5D-5L index values (median 0.68 [IQR 0.00, 1.00], compared to 0.67 [IQR 0.00, 1.00], median difference 0.00 [95% CI - 0.32, 0.32; p = 0.91]) or EQ-VAS scores (median 70 [IQR 0, 93], compared to 70 [IQR 0, 90], median difference 0.00 (95% CI - 31.92, 31.92; p = 0.55). CONCLUSIONS: Helmet noninvasive ventilation did not reduce 180-day mortality or improve HRQoL compared to usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia.

Impact of a national collaborative project to improve the care of mechanically ventilated patients.

This prospective quasi-experimental study from the NASAM (National Approach to Standardize and Improve Mechanical Ventilation) collaborative assessed the impact of evidence-based practices including subglottic suctioning, daily assessment for spontaneous awakening trial (SAT), spontaneous breathing trial (SBT), head of bed elevation, and avoidance of neuromuscular blockers unless otherwise indicated. The study outcomes included VAE (primary) and intensive care unit (ICU) mortality. Changes in daily care process measures and outcomes were evaluated using repeated measures mixed modeling. The results were reported as incident rate ratio (IRR) for each additional month with 95% confidence interval (CI). A comprehensive program that included education on evidence-based practices for optimal care of mechanically ventilated patients with real-time benchmarking of daily care process measures to drive improvement in forty-two ICUs from 26 hospitals in Saudi Arabia (>27,000 days of observation). Compliance with subglottic suctioning, SAT and SBT increased monthly during the project by 3.5%, 2.1% and 1.9%, respectively (IRR 1.035, 95%CI 1.007-1.064, p = 0.0148; 1.021, 95% CI 1.010-1.032, p = 0.0003; and 1.019, 95%CI 1.009-1.029, p = 0.0001, respectively). The use of neuromuscular blockers decreased monthly by 2.5% (IRR 0.975, 95%CI 0.953-0.998, p = 0.0341). The compliance with head of bed elevation was high at baseline and did not change over time. Based on data for 83153 ventilator days, VAE rate was 15.2/1000 ventilator day (95%CI 12.6-18.1) at baseline and did not change during the project (IRR 1.019, 95%CI 0.985-1.053, p = 0.2812). Based on data for 8523 patients; the mortality was 30.4% (95%CI 27.4-33.6) at baseline, and decreased monthly during the project by 1.6% (IRR 0.984, 95%CI 0.973-0.996, p = 0.0067). A national quality improvement collaborative was associated with improvements in daily care processes. These changes were associated with a reduction in mortality but not VAEs. Registration The study is registered in clinicaltrials.gov (NCT03790150).

Characteristics, Management, and Outcomes of Community-Acquired Pneumonia Due to Human Rhinovirus-A Retrospective Study.

Introduction: Human rhinovirus (HRV) can lead to a variety of respiratory illnesses; it is also an uncommon cause of community-acquired pneumonia (CAP). We described the characteristics and outcomes of patients hospitalized for CAP due to HRV. Methods: We retrospectively studied consecutive adult patients admitted to King Abdulaziz Medical City-Riyadh with CAP due to HRV between 2016 and 2019. The diagnosis was made by respiratory multiplex PCR within 48 hours of hospitalization. We compared patients requiring ICU admission to those who did not. Results: One-hundred-and-six patients were studied (peak hospitalization between November and January, median age 71.5 years, hypertension 59%, diabetes 50%, and chronic respiratory disease 44.3%); 16 (15.1%) patients required ICU admission. The median pneumonia severity index score (PSI) was 107, with no significant difference between ICU and nonICU patients. ICU patients had a higher prevalence of tachypnea (62.5% vs. 26.7%, p=0.005), hemoptysis (12.5% vs 0%, p=0.001), and lymphopenia (71.4% vs 26.3%, p=0.01). Chest X-ray on presentation showed bilateral infiltrates in 47/101 (46.5%) patients and unilateral infiltrates in 26/101 (25.7%) patients. Systemic corticosteroids were used in 54.7% of patients (the median initial dose was 120 mg of prednisone equivalent and was higher in nonICU patients). Most (69.2%) ICU patients received mechanical ventilation (median duration of 8 days). Bacterial coinfection (6.6%) and superinfection (3.8%) were rare. The overall hospital mortality was 9.4% (higher for ICU patients: 37.5% vs. 4.4%, p < 0.001). Conclusions: Most patients with CAP due to HRV were elderly and had significant comorbidities. ICU admission was required in almost one in six patients and was associated with higher mortality.

Prevalence and Risk Factors of Venous Thromboembolism in Critically Ill Patients with Severe COVID-19 and the Association between the Dose of Anticoagulants and Outcomes.

Introduction: COVID-19 is characterized by a procoagulant state that increases the risk of venous and arterial thrombosis. The dose of anticoagulants in patients with severe COVID-19 pneumonia without suspected or confirmed thrombosis has been debated. Aim of the study: We evaluated the prevalence, predictors, and outcomes of venous thromboembolism (VTE) in critically ill COVID-19 patients and assessed the association between the dose of anticoagulants and outcomes. Materials and methods: This retrospective cohort included patients with COVID-19 who were admitted to the ICU between March and July 2020. Patients with clinically suspected and confirmed VTE were compared to those not diagnosed to have VTE. Results: The study enrolled 310 consecutive patients with severe COVID-19 pneumonia: age 60.0±15.1 years, 67.1% required mechanical ventilation and 44.7% vasopressors. Most (97.1%) patients received anticoagulants during ICU stay: prophylactic unfractionated heparin (N=106), standard-dose enoxaparin (N=104) and intermediate-dose enoxaparin (N=57). Limb Doppler ultrasound was performed for 49 (15.8%) patients and chest computed tomographic angiography for 62 (20%). VTE was diagnosed in 41 (13.2%) patients; 20 patients had deep vein thrombosis and 23 had acute pulmonary embolism. Patients with VTE had significantly higher D-dimer on ICU admission. On multivariable Cox regression analysis, intermediate-dose enoxaparin versus standard-dose unfractionated heparin or enoxaparin was associated with lower VTE risk (hazard ratio, 0.06; 95% confidence interval, 0.01-0.74) and lower risk of the composite outcome of VTE or hospital mortality (hazard ratio, 0.42; 95% confidence interval, 0.23-0.78; p=0.006). Major bleeding was not different between the intermediate- and prophylactic-dose heparin groups. Conclusions: In our study, clinically suspected and confirmed VTE was diagnosed in 13.2% of critically ill patients with COVID-19. Intermediate-dose enoxaparin versus standard-dose unfractionated heparin or enoxaparin was associated with decreased risk of VTE or hospital mortality.

Standard dosing of enoxaparin versus unfractionated heparin in critically ill patient with COVID-19: a multicenter propensity-score matched study.

BACKGROUND: Thrombotic events are common in critically ill patients with COVID-19 and have been linked with COVID-19- induced hyperinflammatory state. In addition to anticoagulant effects, heparin and its derivatives have various anti-inflammatory and immunomodulatory properties that may affect patient outcomes. This study compared the effectiveness and safety of prophylactic standard-doses of enoxaparin and unfractionated heparin (UFH) in critically ill patients with COVID-19.  METHODS: A multicenter, retrospective cohort study included critically ill adult patients with COVID-19 admitted to the ICU between March 2020 and July 2021. Patients were categorized into two groups based on the type of pharmacological VTE thromboprophylaxis given in fixed doses (Enoxaparin 40 mg SQ every 24 hours versus UFH 5000 Units SQ every 8 hours) throughout their ICU stay. The primary endpoint was all cases of thrombosis. Other endpoints were considered secondary. Propensity score (PS) matching was used to match patients (1:1 ratio) between the two groups based on the predefined criteria. Multivariable logistic, Cox proportional hazards, and negative binomial regression analysis were used as appropriate.  RESULTS: A total of 306 patients were eligible based on the eligibility criteria; 130 patients were included after PS matching (1:1 ratio). Patients who received UFH compared to enoxaparin had higher all thrombosis events at crude analysis (18.3% vs. 4.6%; p-value = 0.02 as well in logistic regression analysis (OR: 4.10 (1.05, 15.93); p-value = 0.04). Although there were no significant differences in all bleeding cases and major bleeding between the two groups (OR: 0.40 (0.07, 2.29); p-value = 0.31 and OR: 1.10 (0.14, 8.56); p-value = 0.93, respectively); however, blood transfusion requirement was higher in the UFH group but did not reach statistical significance (OR: 2.98 (0.85, 10.39); p-value = 0.09). The 30-day and in-hospital mortality were similar between the two groups at Cox hazards regression analysis. In contrast, hospital LOS was longer in the UFH group; however, it did not reach the statistically significant difference (beta coefficient: 0.22; 95% CI: -0.03, 0.48; p-value = 0.09). CONCLUSION: Prophylactic enoxaparin use in critically ill patients with COVID-19 may significantly reduce all thrombosis cases with similar bleeding risk compared to UFH.

Effect of Helmet Noninvasive Ventilation vs Usual Respiratory Support on Mortality Among Patients With Acute Hypoxemic Respiratory Failure Due to COVID-19: The HELMET-COVID Randomized Clinical Trial.

Importance: Helmet noninvasive ventilation has been used in patients with COVID-19 with the premise that helmet interface is more effective than mask interface in delivering prolonged treatments with high positive airway pressure, but data about its effectiveness are limited. Objective: To evaluate whether helmet noninvasive ventilation compared with usual respiratory support reduces mortality in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. Design, Setting, and Participants: This was a multicenter, pragmatic, randomized clinical trial that was conducted in 8 sites in Saudi Arabia and Kuwait between February 8, 2021, and November 16, 2021. Adult patients with acute hypoxemic respiratory failure (n = 320) due to suspected or confirmed COVID-19 were included. The final follow-up date for the primary outcome was December 14, 2021. Interventions: Patients were randomized to receive helmet noninvasive ventilation (n = 159) or usual respiratory support (n = 161), which included mask noninvasive ventilation, high-flow nasal oxygen, and standard oxygen. Main Outcomes and Measures: The primary outcome was 28-day all-cause mortality. There were 12 prespecified secondary outcomes, including endotracheal intubation, barotrauma, skin pressure injury, and serious adverse events. Results: Among 322 patients who were randomized, 320 were included in the primary analysis, all of whom completed the trial. Median age was 58 years, and 187 were men (58.4%). Within 28 days, 43 of 159 patients (27.0%) died in the helmet noninvasive ventilation group compared with 42 of 161 (26.1%) in the usual respiratory support group (risk difference, 1.0% [95% CI, -8.7% to 10.6%]; relative risk, 1.04 [95% CI, 0.72-1.49]; P = .85). Within 28 days, 75 of 159 patients (47.2%) required endotracheal intubation in the helmet noninvasive ventilation group compared with 81 of 161 (50.3%) in the usual respiratory support group (risk difference, -3.1% [95% CI, -14.1% to 7.8%]; relative risk, 0.94 [95% CI, 0.75-1.17]). There were no significant differences between the 2 groups in any of the prespecified secondary end points. Barotrauma occurred in 30 of 159 patients (18.9%) in the helmet noninvasive ventilation group and 25 of 161 (15.5%) in the usual respiratory support group. Skin pressure injury occurred in 5 of 159 patients (3.1%) in the helmet noninvasive ventilation group and 10 of 161 (6.2%) in the usual respiratory support group. There were 2 serious adverse events in the helmet noninvasive ventilation group and 1 in the usual respiratory support group. Conclusions and Relevance: Results of this study suggest that helmet noninvasive ventilation did not significantly reduce 28-day mortality compared with usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. However, interpretation of the findings is limited by imprecision in the effect estimate, which does not exclude potentially clinically important benefit or harm. Trial Registration: ClinicalTrials.gov Identifier: NCT04477668.

The impact of HMG-CoA reductase inhibitors use on the clinical outcomes in critically ill patients with COVID-19: A multicenter, cohort study.

Background: The cardiovascular complications of Coronavirus Disease 2019 (COVID-19) may be attributed to the hyperinflammatory state leading to increased mortality in patients with COVID-19. HMG-CoA Reductase Inhibitors (statins) are known to have pleiotropic and anti-inflammatory effects and may have antiviral activity along with their cholesterol-lowering activity. Thus, statin therapy is potentially a potent adjuvant therapy in COVID-19 infection. This study investigated the impact of statin use on the clinical outcome of critically ill patients with COVID-19. Methods: A multicenter, retrospective cohort study of all adult critically ill patients with confirmed COVID-19 who were admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on the statin use during ICU stay and were matched with a propensity score based on patient's age and admission APACHE II and SOFA scores. The primary endpoint was in-hospital mortality, while 30 day mortality, ventilator-free days (VFDs) at 30 days, and ICU complications were secondary endpoints. Results: A total of 1,049 patients were eligible; 502 patients were included after propensity score matching (1:1 ratio). The in-hospital mortality [hazard ratio 0.69 (95% CI 0.54, 0.89), P = 0.004] and 30-day mortality [hazard ratio 0.75 (95% CI 0.58, 0.98), P = 0.03] were significantly lower in patients who received statin therapy on multivariable cox proportional hazards regression analysis. Moreover, patients who received statin therapy had lower odds of hospital-acquired pneumonia [OR 0.48 (95% CI 0.32, 0.69), P < 0.001], lower levels of inflammatory markers on follow-up, and no increased risk of liver injury. Conclusion: The use of statin therapy during ICU stay in critically ill patients with COVID-19 may have a beneficial role and survival benefit with a good safety profile.

A case report on the association between QTc prolongation and remdesivir therapy in a critically ill patient.

Remdesivir is a direct-acting inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase that is used to treat severe COVID-19 infections. We report a patient with severe COVID-19 pneumonia who experienced palpitations and syncope two days after starting remdesivir therapy. The QTc interval was prolonged on the Electrocardiogram (ECG) without any significant electrolyte abnormalities or concomitant use of medications with QTc prolongation. Although the cardiac side effects of remdesivir therapy have been well documented, the link between remdesivir therapy and QTc interval prolongation in patients with severe COVID-19 has only been observed in a few cases. Because this arrhythmia has the potential to result in sudden cardiac death, practitioners should be aware of the QTc interval prolongation associated with remdesivir therapy.

The association of timing of pharmacological prophylaxis and venous thromboembolism in patients with moderate-to-severe traumatic brain injury: A retrospective cohort study.

OBJECTIVES: Patients with traumatic brain injury (TBI) have an increased risk for venous thromboembolism (VTE). The current guidelines recommend pharmacologic prophylaxis, but its timing remains unclear. METHODS: In this retrospective cohort study, patients with moderate-to-severe TBI admitted to a tertiary care intensive care unit between 2016 and 2019 were categorized into two groups according to the timing of pharmacologic prophylaxis: early if prophylaxis was given within 72 h from hospital admission and late if after 72 h. RESULTS: Of the 322 patients in the cohort, 46 (14.3%) did not receive pharmacological prophylaxis, mainly due to early brain death; 152 (47.2%) received early pharmacologic prophylaxis and 124 (38.5%) received late prophylaxis. Predictors of late pharmacologic prophylaxis were lower body mass index, intracerebral hemorrhage (odds ratio [OR], 3.361; 95% confidence interval [CI], 1.269-8.904), hemorrhagic contusion (OR, 3.469; 95% CI, 1.039-11.576), and lower platelet count. VTE was diagnosed in 43 patients on a median of 10 days after trauma (Q1, Q3: 5, 15): 6.6% of the early prophylaxis group and 26.6% of the late group (P < 0.001). On multivariable logistic regression analysis, the predictors of VTE were Acute Physiology and Chronic Health Evaluation II score, subarachnoid hemorrhage, and late versus early pharmacologic prophylaxis (OR, 3.858; 95% CI, 1.687-8.825). The late prophylaxis group had higher rate of tracheostomy, longer duration of mechanical ventilation and stay in the hospital, lower discharge Glasgow coma scale, but similar survival, compared with the early group. CONCLUSIONS: Late prophylaxis (>72 h) was associated with higher VTE rate in patients with moderate-to-severe TBI, but not with higher mortality.