Incidence and Clinical Outcomes of New-Onset Atrial Fibrillation in Critically lll Patients with COVID-19: A Multicenter Cohort Study - New-Onset Atrial Fibrillation and COVID-19.

Atrial fibrillation (Afib) can contribute to a significant increase in mortality and morbidity in critically ill patients. Thus, our study aims to investigate the incidence and clinical outcomes associated with the new-onset Afib in critically ill patients with COVID-19. A multicenter, retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the intensive care units (ICUs) from March, 2020 to July, 2021. Patients were categorized into two groups (new-onset Afib vs control). The primary outcome was the in-hospital mortality. Other outcomes were secondary, such as mechanical ventilation (MV) duration, 30-day mortality, ICU length of stay (LOS), hospital LOS, and complications during stay. After propensity score matching (3:1 ratio), 400 patients were included in the final analysis. Patients who developed new-onset Afib had higher odds of in-hospital mortality (OR 2.76; 95% CI: 1.49-5.11, P = .001). However, there was no significant differences in the 30-day mortality. The MV duration, ICU LOS, and hospital LOS were longer in patients who developed new-onset Afib (beta coefficient 0.52; 95% CI: 0.28-0.77; P < .0001,beta coefficient 0.29; 95% CI: 0.12-0.46; P < .001, and beta coefficient 0.35; 95% CI: 0.18-0.52; P < .0001; respectively). Moreover, the control group had significantly lower odds of major bleeding, liver injury, and respiratory failure that required MV. New-onset Afib is a common complication among critically ill patients with COVID-19 that might be associated with poor clinical outcomes; further studies are needed to confirm these findings.

Evaluation of Early Tocilizumab Effect on Multiorgan Dysfunction in Critically Ill Patients With COVID-19: A Propensity Score-Matched Study.

Background: Tocilizumab (TCZ) has been proposed as potential rescue therapy for severe COVID-19. No previous study has primarily assessed the role of TCZ in preventing severe COVID-19-related multiorgan dysfunction. Hence, this multicenter cohort study aimed to evaluate the effectiveness of TCZ early use versus standard of care in preventing severe COVID-19-related multiorgan dysfunction in COVID-19 critically ill patients during intensive care unit (ICU) stay. Methods: A multicenter, retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the ICUs. Patients were categorized into two groups, the treatment group includes patients who received early TCZ therapy within 24 hours of ICU admission and the control group includes patients who received standard of care. The primary outcome was the multiorgan dysfunction on day three of the ICU admission. The secondary outcomes were 30-day, and in-hospital mortality, ventilator-free days, hospital length of stay (LOS), ICU LOS, and ICU-related complications. Results: After propensity score matching, 300 patients were included in the analysis based on predefined criteria with a ratio of 1:2. Patients who received TCZ had lower multiorgan dysfunction score on day three of ICU admission compared to the control group (beta coefficient: -0.13, 95% CI: -0.26, -0.01, P-value = 0.04). Moreover, respiratory failure requiring MV was statistically significantly lower in patients who received early TCZ compared to the control group (OR 0.52; 95% CI 0.31, 0.91, P-value = 0.02). The 30-day and in-hospital mortality were significantly lower in patients who received TCZ than those who did not (HR 0.56; 95% CI 0.37, 0.85, P-value = 0 .006 and HR 0.54; 95% CI 0.36, 0.82, P-value = 0.003, respectively). Conclusion: In addition to the mortality benefits associated with early TCZ use within 24 hours of ICU admission, the use of TCZ was associated with a significantly lower multiorgan dysfunction score on day three of ICU admission in critically ill patients with COVID-19.

Carbapenemase-Producing Klebsiella pneumoniae in COVID-19 Intensive Care Patients: Identification of IncL-VIM-1 Plasmid in Previously Non-Predominant Sequence Types.

During the COVID-19 pandemic, intensive care units (ICUs) operated at or above capacity, and the number of ICU patients coinfected by nosocomial microorganisms increased. Here, we characterize the population structure and resistance mechanisms of carbapenemase-producing Klebsiella pneumoniae (CP-Kpn) from COVID-19 ICU patients and compare them to pre-pandemic populations of CP-Kpn. We analyzed 84 CP-Kpn isolates obtained during the pandemic and 74 CP-Kpn isolates obtained during the pre-pandemic period (2019) by whole genome sequencing, core genome multilocus sequence typing, plasmid reconstruction, and antibiotic susceptibility tests. More CP-Kpn COVID-19 isolates produced OXA-48 (60/84, 71.4%) and VIM-1 (18/84, 21.4%) than KPC (8/84, 9.5%). Fewer pre-pandemic CP-Kpn isolates produced VIM-1 (7/74, 9.5%). Cefiderocol (97.3-100%) and plazomicin (97.5-100%) had the highest antibiotic activity against pandemic and pre-pandemic isolates. Sequence type 307 (ST307) was the most widely distributed ST in both groups. VIM-1-producing isolates belonging to ST307, ST17, ST321 and ST485, (STs infrequently associated to VIM-1) were detected during the COVID-19 period. Class 1 integron Int1-blaVIM-1-aac(6')-1b-dfrB1-aadAI-catB2-qacEΔ1/sul1, found on an IncL plasmid of approximately 70,000 bp, carried blaVIM-1 in ST307, ST17, ST485, and ST321 isolates. Thus, CP-Kpn populations from pandemic and pre-pandemic periods have similarities. However, VIM-1 isolates associated with atypical STs increased during the pandemic, which warrants additional monitoring and surveillance.

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.

Evaluation of inhaled nitric oxide (iNO) treatment for moderate-to-severe ARDS in critically ill patients with COVID-19: a multicenter cohort study.

BACKGROUND: Inhaled nitric oxide (iNO) is used as rescue therapy in patients with refractory hypoxemia due to severe COVID-19 acute respiratory distress syndrome (ARDS) despite the recommendation against the use of this treatment. To date, the effect of iNO on the clinical outcomes of critically ill COVID-19 patients with moderate-to-severe ARDS remains arguable. Therefore, this study aimed to evaluate the use of iNO in critically ill COVID-19 patients with moderate-to-severe ARDS. METHODS: This multicenter, retrospective cohort study included critically ill adult patients with confirmed COVID-19 treated from March 01, 2020, until July 31, 2021. Eligible patients with moderate-to-severe ARDS were subsequently categorized into two groups based on inhaled nitric oxide (iNO) use throughout their ICU stay. The primary endpoint was the improvement in oxygenation parameters 24 h after iNO use. Other outcomes were considered secondary. Propensity score matching (1:2) was used based on the predefined criteria. RESULTS: A total of 1598 patients were screened, and 815 were included based on the eligibility criteria. Among them, 210 patients were matched based on predefined criteria. Oxygenation parameters (PaO2, FiO2 requirement, P/F ratio, oxygenation index) were significantly improved 24 h after iNO administration within a median of six days of ICU admission. However, the risk of 30-day and in-hospital mortality were found to be similar between the two groups (HR: 1.18; 95% CI: 0.77, 1.82; p = 0.45 and HR: 1.40; 95% CI: 0.94, 2.11; p= 0.10, respectively). On the other hand, ventilator-free days (VFDs) were significantly fewer, and  ICU and hospital LOS were significantly longer in the iNO group. In addition, patients who received iNO had higher odds of acute kidney injury (AKI) (OR (95% CI): 2.35 (1.30, 4.26), p value = 0.005) and hospital/ventilator-acquired pneumonia (OR (95% CI): 3.2 (1.76, 5.83), p value = 0.001). CONCLUSION: In critically ill COVID-19 patients with moderate-to-severe ARDS, iNO rescue therapy is associated with improved oxygenation parameters but no mortality benefits. Moreover, iNO use is associated with higher odds of AKI, pneumonia, longer LOS, and fewer VFDs.

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.

Evaluation of Low-Dose Aspirin use among Critically Ill Patients with COVID-19: A Multicenter Propensity Score Matched Study.

BACKGROUND: Aspirin is widely used as a cardioprotective agent due to its antiplatelet and anti-inflammatory properties. The literature has assessed and evaluated its role in hospitalized COVID-19 patients. However, no data are available regarding its role in COVID-19 critically ill patients. This study aimed to evaluate the use of low-dose aspirin (81-100 mg) and its impact on outcomes in critically ill patients with COVID-19. METHOD: A multicenter, retrospective cohort study of all critically ill adult patients with confirmed COVID-19 admitted to intensive care units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on aspirin use during ICU stay. The primary outcome was in-hospital mortality, and other outcomes were considered secondary. Propensity score matching was used (1:1 ratio) based on the selected criteria. RESULTS: A total of 1033 patients were eligible, and 352 patients were included after propensity score matching. The in-hospital mortality (HR 0.73 [0.56, 0.97], p = 0.03) was lower in patients who received aspirin during stay. Conversely, patients who received aspirin had a higher odds of major bleeding than those in the control group (OR 2.92 [0.91, 9.36], p = 0.07); however, this was not statistically significant. Additionally, subgroup analysis showed a possible mortality benefit for patients who used aspirin therapy prior to hospitalization and continued during ICU stay (HR 0.72 [0.52, 1.01], p = 0.05), but not with the new initiation of aspirin (HR 1.22 [0.68, 2.20], p = 0.50). CONCLUSION: Continuation of aspirin therapy during ICU stay in critically ill patients with COVID-19 who were receiving it prior to ICU admission may have a mortality benefit; nevertheless, it may be associated with an increased risk of significant bleeding. Appropriate evaluation for safety versus benefits of utilizing aspirin therapy during ICU stay in COVID19 critically ill patients is highly recommended.

Comparison between standard Vs. Escalated dose venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19: A two centers, observational study.

INTRODUCTION: The risk of mortality in patients with COVID-19 was found to be significantly higher in patients who experienced thromboembolic events. Thus, several guidelines recommend using prophylactic anticoagulants in all COVID-19 hospitalized patients. However, there is uncertainty about the appropriate dosing regimen and safety of anticoagulation in critically ill patients with COVID-19. Thus, this study aims to compare the effectiveness and safety of standard versus escalated dose pharmacological venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19. METHODS: A two-center retrospective cohort study including critically ill patients aged ≥ 18-years with confirmed COVID-19 admitted to the intensive care unit (ICU) at two tertiary hospitals in Saudi Arabia from March 1st, 2020, until January 31st, 2021. Patients who received either Enoxaparin 40 mg daily or Unfractionated heparin 5000 Units three times daily were grouped under the "standard dose VTE prophylaxis and patients who received higher than the standard dose but not as treatment dose were grouped under "escalated VTE prophylaxis dose". The primary outcome was the occurance of thrombotic events, and the secondary outcomes were bleeding, mortality, and other ICU-related complications. RESULTS: A total of 758 patients were screened; 565 patients were included in the study. We matched 352 patients using propensity score matching (1:1). In patients who received escalated dose pharmacological VTE prophylaxis, any case of thrombosis and VTE were similar between the two groups (OR 1.22;95 %CI 0.52-2.86; P = 0.64 and OR 0.75; 95% CI 0.16-3.38; P = 0.70 respectively). However, the odds of minor bleeding was higher in patients who received escalated VTE prophylaxis dose (OR 3.39; 95% CI 1.08-10.61; P = 0.04). There was no difference in the 30-day mortality nor in-hospital mortality between the two groups (HR 1.17;95 %CI0.79-1.73; P = 0.43 and HR 1.08;95 %CI 0.76-1.53; P = 0.83, respectively). CONCLUSION: Escalated-dose pharmacological VTE prophylaxis in critically ill patients with COVID-19 was not associated with thrombosis, or mortality benefits but led to an increased risk of minor bleeding. This study supports previous evidence regarding the optimal dosing VTE pharmacological prophylaxis regimen for critically ill patients with COVID-19.

Association between tocilizumab and emerging multidrug-resistant organisms in critically ill patients with COVID-19: A multicenter, retrospective cohort study.

BACKGROUND: Tocilizumab is an IgG1 class recombinant humanized monoclonal antibody that directly inhibits the IL-6 receptor. Several randomized clinical trials have evaluated its safety and efficacy in patients with coronavirus disease 2019 (COVID-19), and these studies demonstrate conflicting results. Our study aimed to determine the association between tocilizumab treatment and microbial isolation and emergence of multidrug-resistant bacteria in critically ill patients with COVID-19. METHODS: A multicenter retrospective cohort study was conducted at two tertiary government hospitals in Saudi Arabia. All critically ill patients admitted to intensive care units with a positive COVID-19 PCR test between March 1 and December 31, 2020, who met study criteria were included. Patients who received tocilizumab were compared to those who did not receive it. RESULTS: A total of 738 patients who met our inclusion criteria were included in the analysis. Of these, 262 (35.5%) received tocilizumab, and 476 (64.5%) were included in the control group. Patients who received tocilizumab had higher odds for microbial isolation (OR 1.34; 95% CI 0.91-1.94, p = 0.13); however, the difference was not statistically significant. Development of resistant organisms (OR 1.00; 95% CI 0.51-1.98, p = 0.99) or detection of carbapenem-resistant Enterobacteriaceae (CRE) (OR 0.67; 95% CI 0.29-1.54, p = 0.34) was not statistically significant between the two groups. CONCLUSIONS: Tocilizumab use in critically ill patients with COVID-19 is not associated with higher microbial isolation, the emergence of resistant organisms, or the detection of CRE organisms.

Single versus multiple doses of Tocilizumab in critically ill patients with coronavirus disease 2019 (COVID-19): A two-center, retrospective cohort study.

PURPOSE: To evaluate the effectiveness and safety of the optimal tocilizumab dosing regimen. METHODS: A two-center, retrospective cohort study, for COVID19 critically ill patients admitted to the intensive care units (ICUs). We included critically ill patients aged 18 years or older who received tocilizumab during ICU stay. Patients were divided into two groups based on the number of the received tocilizumab doses. The primary outcome was the in-hospital and 30-day mortality. Propensity score (PS) matching was used (1:1 ratio) based on the selected criteria. RESULTS: A total of 298 patients were included in the study; 70.4% (210 patients) received a single dose of tocilizumab. After adjusting for possible confounders, the 30-day mortality (HR 0.79 95% CI 0.43-1.45 P = 0.44) and in-hospital mortality (HR 0.81; 95% CI 0.46-1.49; P = 0.53) were not significantly different between the two groups. On the flip side, patients who received multiple doses had higher pneumonia odds than a single dose (OR 3.81; 95% CI 1.79-8.12 P = 0.0005). CONCLUSION: Repeating tocilizumab doses were not associated with a mortality benefit in COVID-19 critically ill patients, but it was associated with higher odds of pneumonia compared to a single dose.

Evaluation of thiamine as adjunctive therapy in COVID-19 critically ill patients: a two-center propensity score matched study.

BACKGROUND: Thiamine is a precursor of the essential coenzyme thiamine pyrophosphate required for glucose metabolism; it improves the immune system function and has shown to reduce the risk of several diseases. The role of thiamine in critically ill septic patient has been addressed in multiple studies; however, it's role in COVID-19 patients is still unclear. The aim of this study was to evaluate the use of thiamine as an adjunctive therapy on mortality in COVID-19 critically ill patients. METHODS: This is a two-center, non-interventional, retrospective cohort study for critically ill patients admitted to intensive care units (ICUs) with a confirmed diagnosis of COVID19. All patients aged 18 years or older admitted to ICUs between March 1, 2020, and December 31, 2020, with positive PCR COVID-19 were eligible for inclusion. We investigated thiamine use as an adjunctive therapy on the clinical outcomes in critically ill COVID-19 patients after propensity score matching. RESULTS: A total of 738 critically ill patients with COVID-19 who had been admitted to ICUs were included in the study. Among 166 patients matched using the propensity score method, 83 had received thiamine as adjunctive therapy. There was significant association between thiamine use with in-hospital mortality (OR = 0.39; 95% CI 0.19-0.78; P value = 0.008) as well as the 30-day mortality (OR = 0.37; 95% CI 0.18-0.78; P value = 0.009). Moreover, patients who received thiamine as an adjunctive therapy were less likely to have thrombosis during ICU stay [OR (95% CI) 0.19 (0.04-0.88), P value = 0.03]. CONCLUSION: Thiamine use as adjunctive therapy may have potential survival benefits in critically ill patients with COVID-19. Additionally, it was associated with a lower incidence of thrombosis. Further interventional studies are required to confirm these findings.

Intensive Care Unit Built Environments: A Comprehensive Literature Review (2005-2020).

BACKGROUND: The intensive care environment in hospitals has been the subject of significant empirical and qualitative research in the 2005-2020 period. Particular attention has been devoted to the role of infection control, family engagement, staff performance, and the built environment ramifications of the recent COVID-19 global pandemic. A comprehensive review of this literature is reported summarizing recent advancements in this rapidly expanding body of knowledge. PURPOSE AND AIM: This comprehensive review conceptually structures the recent medical intensive care literature to provide conceptual clarity and identify current priorities and future evidence-based research and design priorities. METHOD AND RESULT: Each source reviewed was classified as one of the five types-opinion pieces/essays, cross-sectional empirical investigations, nonrandomized comparative investigations, randomized studies, and policy review essays-and into nine content categories: nature engagement and outdoor views; family accommodations; intensive care unit (ICU), neonatal ICU, and pediatric ICU spatial configuration and amenity; noise considerations; artificial and natural lighting; patient safety and infection control; portable critical care field hospitals and disaster mitigation facilities including COVID-19; ecological sustainability; and recent planning and design trends and prognostications. CONCLUSIONS: Among the findings embodied in the 135 literature sources reviewed, single-bed ICU rooms have increasingly become the norm; family engagement in the ICU experience has increased; acknowledgment of the therapeutic role of staff amenities; exposure to nature, view, and natural daylight has increased; the importance of ecological sustainability; and pandemic concerns have increased significantly in the wake of the coronavirus pandemic. Discussion of the results of this comprehensive review includes topics noticeably overlooked or underinvestigated in the 2005-2020 period and priorities for future research.

Clinical features and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19): A multicenter cohort study.

BACKGROUND: Coronavirus disease-19 (COVID-19) manifested by a broad spectrum of symptoms, ranging from asymptomatic manifestations to severe illness and death. The purpose of the study was to extensively describe the clinical features and outcomes in critically ill patients with COVID-19 in Saudi Arabia. METHOD: This was a multicenter, non-interventional cohort study for all critically ill patients aged 18 years or older, admitted to intensive care units (ICUs) between March 1 to August 31, 2020, with an objectively confirmed diagnosis of COVID-19. The diagnosis of COVID-19 was confirmed by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) on nasopharyngeal and/or throat swabs. Multivariate logistic regression and generalized linear regression were used. We considered a P value of <0.05 statistically significant. RESULTS: A total of 560 patients met the inclusion criteria. An extensive list of clinical features was associated with higher 30-day ICU mortality rates, such as requiring mechanical ventilation (MV) or developing acute kidney injury within 24 hours of ICU admission, higher body temperature, white blood cells, blood glucose level, serum creatinine, fibrinogen, procalcitonin, creatine phosphokinase, aspartate aminotransferase, and total iron-binding capacity. During ICU stay, the most common complication was respiratory failure that required MV (71.4%), followed by acute kidney injury (AKI) and thrombosis with a proportion of 46.8% and 11.4%, respectively. CONCLUSION: Among patients with COVID-19 who were admitted to the ICU, several variables were associated with an increased risk of ICU mortality at 30 days. Respiratory failure that required MV, AKI, and thrombosis were the most common complications during ICU stay.