Ketamine-based Sedation Use in Mechanically Ventilated Critically Ill Patients with COVID-19: A Multicenter Cohort Study.

Backgrounds: Ketamine possesses analgesia, anti-inflammation, anticonvulsant, and neuroprotection properties. However, the evidence that supports its use in mechanically ventilated critically ill patients with COVID-19 is insufficient. The study's goal was to assess ketamine's effectiveness and safety in critically ill, mechanically ventilated (MV) patients with COVID-19. Methods: Adult critically ill patients with COVID-19 were included in a multicenter retrospective-prospective cohort study. Patients admitted between March 1, 2020, and July 31, 2021, to five ICUs in Saudi Arabia were included. Eligible patients who required MV within 24 hours of ICU admission were divided into two sub-cohort groups based on their use of ketamine (Control vs. Ketamine). The primary outcome was the length of stay (LOS) in the hospital. P/F ratio differences, lactic acid normalization, MV duration, and mortality were considered secondary outcomes. Propensity score (PS) matching was used (1:2 ratio) based on the selected criteria. Results: In total, 1,130 patients met the eligibility criteria. Among these, 1036 patients (91.7 %) were in the control group, whereas 94 patients (8.3 %) received ketamine. The total number of patients after PS matching, was 264 patients, including 88 patients (33.3 %) who received ketamine. The ketamine group's LOS was significantly lower (beta coefficient (95 % CI): -0.26 (-0.45, -0.07), P = 0.008). Furthermore, the PaO2/FiO2 ratio significantly improved 24 hours after the start of ketamine treatment compared to the pre-treatment period (6 hours) (124.9 (92.1, 184.5) vs. 106 (73.1, 129.3; P = 0.002). Additionally, the ketamine group had a substantially shorter mean time for lactic acid normalization (beta coefficient (95 % CI): -1.55 (-2.42, -0.69), P 0.01). However, there were no significant differences in the duration of MV or mortality. Conclusions: Ketamine-based sedation was associated with lower hospital LOS and faster lactic acid normalization but no mortality benefits in critically ill patients with COVID-19. Thus, larger prospective studies are recommended to assess the safety and effectiveness of ketamine as a sedative in critically ill adult patients.

Dexamethasone versus methylprednisolone for multiple organ dysfunction in COVID-19 critically ill patients: a multicenter propensity score matching study.

BACKGROUND: Dexamethasone usually recommended for patients with severe coronavirus disease 2019 (COVID-19) to reduce short-term mortality. However, it is uncertain if another corticosteroid, such as methylprednisolone, may be utilized to obtain better clinical outcome. This study assessed dexamethasone's clinical and safety outcomes compared to methylprednisolone. METHODS: A multicenter, retrospective cohort study was conducted between March 01, 2020, and July 31, 2021. It included adult COVID-19 patients who were initiated on either dexamethasone or methylprednisolone therapy within 24 h of intensive care unit (ICU) admission. The primary outcome was the progression of multiple organ dysfunction score (MODS) on day three of ICU admission. Propensity score (PS) matching was used (1:3 ratio) based on the patient's age and MODS within 24 h of ICU admission. RESULTS: After Propensity Score (PS) matching, 264 patients were included; 198 received dexamethasone, while 66 patients received methylprednisolone within 24 h of ICU admission. In regression analysis, patients who received methylprednisolone had a higher MODS on day three of ICU admission than those who received dexamethasone (beta coefficient: 0.17 (95% CI 0.02, 0.32), P = 0.03). Moreover, hospital-acquired infection was higher in the methylprednisolone group (OR 2.17, 95% CI 1.01, 4.66; p = 0.04). On the other hand, the 30-day and the in-hospital mortality were not statistically significant different between the two groups. CONCLUSION: Dexamethasone showed a lower MODS on day three of ICU admission compared to methylprednisolone, with no statistically significant difference in mortality.

Survival implications vs. complications: unraveling the impact of vitamin D adjunctive use in critically ill patients with COVID-19-A multicenter cohort study.

Background: Despite insufficient evidence, vitamin D has been used as adjunctive therapy in critically ill patients with COVID-19. This study evaluates the effectiveness and safety of vitamin D as an adjunctive therapy in critically ill COVID-19 patients. Methods: A multicenter retrospective cohort study that included all adult COVID-19 patients admitted to the intensive care units (ICUs) between March 2020 and July 2021. Patients were categorized into two groups based on their vitamin D use throughout their ICU stay (control vs. vitamin D). The primary endpoint was in-hospital mortality. Secondary outcomes were the length of stay (LOS), mechanical ventilation (MV) duration, and ICU-acquired complications. Propensity score (PS) matching (1:1) was used based on the predefined criteria. Multivariable logistic, Cox proportional hazards, and negative binomial regression analyses were employed as appropriate. Results: A total of 1,435 patients were included in the study. Vitamin D was initiated in 177 patients (12.3%), whereas 1,258 patients did not receive it. A total of 288 patients were matched (1:1) using PS. The in-hospital mortality showed no difference between patients who received vitamin D and the control group (HR 1.22, 95% CI 0.87-1.71; p = 0.26). However, MV duration and ICU LOS were longer in the vitamin D group (beta coefficient 0.24 (95% CI 0.00-0.47), p = 0.05 and beta coefficient 0.16 (95% CI -0.01 to 0.33), p = 0.07, respectively). As an exploratory outcome, patients who received vitamin D were more likely to develop major bleeding than those who did not [OR 3.48 (95% CI 1.10, 10.94), p = 0.03]. Conclusion: The use of vitamin D as adjunctive therapy in COVID-19 critically ill patients was not associated with survival benefits but was linked with longer MV duration, ICU LOS, and higher odds of major bleeding.

Evaluation of the use of methylprednisolone and dexamethasone in asthma critically ill patients with COVID-19: a multicenter cohort study.

BACKGROUND: Previous studies have shown mortality benefits with corticosteroids in Coronavirus disease-19 (COVID-19). However, there is inconsistency regarding the use of methylprednisolone over dexamethasone in COVID-19, and this has not been extensively evaluated in patients with a history of asthma. This study aims to investigate and compare the effectiveness and safety of methylprednisolone and dexamethasone in critically ill patients with asthma and COVID-19. METHODS: The primary endpoint was the in-hospital mortality. Other endpoints include 30-day mortality, respiratory failure requiring mechanical ventilation (MV), acute kidney injury (AKI), acute liver injury, length of stay (LOS), ventilator-free days (VFDs), and hospital-acquired infections. Propensity score (PS) matching, and regression analyses were used. RESULTS: A total of one hundred-five patients were included. Thirty patients received methylprednisolone, whereas seventy-five patients received dexamethasone. After PS matching (1:1 ratio), patients who received methylprednisolone had higher but insignificant in-hospital mortality in both crude and logistic regression analysis, [(35.0% vs. 18.2%, P = 0.22) and (OR 2.31; CI: 0.56 - 9.59; P = 0.25), respectively]. There were no statistically significant differences in the 30-day mortality, respiratory failure requiring MV, AKI, acute liver injury, ICU LOS, hospital LOS, and hospital-acquired infections. CONCLUSIONS: Methylprednisolone in COVID-19 patients with asthma may lead to increased in-hospital mortality and shorter VFDs compared to dexamethasone; however, it failed to reach statistical significance. Therefore, it is necessary to interpret these data cautiously, and further large-scale randomized clinical trials are needed to establish more conclusive evidence and support these conclusions.

When antivirals backfire: An evaluation of favipiravir's clinical outcomes in critically ill patients with COVID-19: A multicenter cohort study.

BACKGROUND: Favipiravir is an oral antiviral, that might treat COVID-19 by enhancing viral eradication, particularly in patients with mild-to-moderate disease. Yet, the findings on the use of favipiravir in critically ill patients with COVID-19 are inconsistent. Therefore, this study aimed to assess the effectiveness and safety of favipiravir in critically ill patients with COVID-19. METHOD: A multicenter retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the intensive care units (ICUs) was conducted from March 2020 to July 2021. Patients were categorized based on favipiravir use (control vs. favipiravir). The primary outcome was in-hospital mortality. Secondary outcomes included mechanical ventilation (MV) duration, 30-day mortality, ICU length of stay (LOS), hospital LOS, and complications during the stay. RESULTS: After propensity score (PS) matching (1:1 ratio), 146 patients were included in the final analysis. A higher in-hospital and 30-day mortality were observed in patients receiving favipiravir compared to the control group at crude analysis (65.3% vs. 43.8%; P-value=0.009 and 56.3% vs. 40.3; P-value=0.06, respectively); however, no differences were observed using multivariable Cox proportional hazards regression analysis (HR 1.17; 95% CI 0.73, 1.87; P-value =0.51 and HR 0.86; 95% CI 0.53, 1.39; P-value=0.53, respectively). Conversely, the MV duration and ICU LOS were longer in patients who received favipiravir than the control group (ß coefficient 0.51; CI 0.09, 0.92; P-value = 0.02, ß coefficient 0.41; CI 0.17, 0.64; P-value = 0.0006, respectively). Complications during the stay were comparable between the two groups. CONCLUSION: The use of favipiravir in critically ill patients with COVID-19 did not demonstrate a reduction in mortality; instead, it was linked with longer MV duration and ICU stay. This finding suggests limiting favipiravir use to infections where it is more effective, other than COVID-19. Further randomized clinical trials are needed to confirm these findings.

Doxycycline's Potential Role in Reducing Thrombosis and Mortality in Critically Ill Patients With COVID-19: A Multicenter Cohort Study.

Doxycycline has revealed potential effects in animal studies to prevent thrombosis and reduce mortality. However, less is known about its antithrombotic role in patients with COVID-19. Our study aimed to evaluate doxycycline's impact on clinical outcomes in critically ill patients with COVID-19. A multicenter retrospective cohort study was conducted between March 1, 2020, and July 31, 2021. Patients who received doxycycline in intensive care units (ICUs) were compared to patients who did not (control). The primary outcome was the composite thrombotic events. The secondary outcomes were 30-day and in-hospital mortality, length of stay, ventilator-free days, and complications during ICU stay. Propensity score (PS) matching was used based on the selected criteria. Logistic, negative binomial, and Cox proportional hazards regression analyses were used as appropriate. After PS (1:3) matching, 664 patients (doxycycline n = 166, control n = 498) were included. The number of thromboembolic events was lower in the doxycycline group (OR: 0.54; 95% CI: 0.26-1.08; P = .08); however, it failed to reach to a statistical significance. Moreover, D-dimer levels and 30-day mortality were lower in the doxycycline group (beta coefficient [95% CI]: -0.22 [-0.46, 0.03; P = .08]; HR: 0.73; 95% CI: 0.52-1.00; P = .05, respectively). In addition, patients who received doxycycline had significantly lower odds of bacterial/fungal pneumonia (OR: 0.65; 95% CI: 0.44-0.94; P = .02). The use of doxycycline as adjunctive therapy in critically ill patients with COVID-19 might may be a desirable therapeutic option for thrombosis reduction and survival benefits.

The effect of oseltamivir use in critically ill patients with COVID-19: A multicenter propensity score-matched study.

Background: Oseltamivir has been used as adjunctive therapy in the management of patients with COVID-19. However, the evidence about using oseltamivir in critically ill patients with severe COVID-19 remains scarce. This study aims to evaluate the effectiveness and safety of oseltamivir in critically ill patients with COVID-19. Methods: This multicenter, retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the intensive care unit (ICU). Patients were categorized into two groups based on oseltamivir use within 48 hours of ICU admission (Oseltamivir vs. Control). The primary endpoint was viral load clearance. Results: A total of 226 patients were matched into two groups based on their propensity score. The time to COVID-19 viral load clearance was shorter in patients who received oseltamivir (11 vs. 16 days, p = 0.042; beta coefficient: -0.84, 95%CI: (-1.33, 0.34), p = 0.0009). Mechanical ventilation (MV) duration was also shorter in patients who received oseltamivir (6.5 vs. 8.5 days, p = 0.02; beta coefficient: -0.27, 95% CI: [-0.55,0.02], P = 0.06). In addition, patients who received oseltamivir had lower odds of hospital/ventilator-acquired pneumonia (OR:0.49, 95% CI:(0.283,0.861), p = 0.01). On the other hand, there were no significant differences between the groups in the 30-day and in-hospital mortality. Conclusion: Oseltamivir was associated with faster viral clearance and shorter MV duration without safety concerns in critically ill COVID-19 patients.

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.

The clinical outcomes of COVID-19 critically ill patients co-infected with other respiratory viruses: a multicenter, cohort study.

BACKGROUND: Previous studies have shown that non-critically ill COVID-19 patients co-infected with other respiratory viruses have poor clinical outcomes. However, limited studies focused on this co-infections in critically ill patients. This study aims to evaluate the clinical outcomes of critically ill patients infected with COVID-19 and co-infected by other respiratory viruses. METHODS: A multicenter retrospective cohort study was conducted for all adult patients with COVID-19 who were hospitalized in the ICUs between March, 2020 and July, 2021. Eligible patients were sub-categorized into two groups based on simultaneous co-infection with other respiratory viruses throughout their ICU stay. Influenza A or B, Human Adenovirus (AdV), Human Coronavirus (i.e., 229E, HKU1, NL63, or OC43), Human Metapneumovirus, Human Rhinovirus/Enterovirus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Parainfluenza virus, and Respiratory Syncytial Virus (RSV) were among the respiratory viral infections screened. Patients were followed until discharge from the hospital or in-hospital death. RESULTS: A total of 836 patients were included in the final analysis. Eleven patients (1.3%) were infected concomitantly with other respiratory viruses. Rhinovirus/Enterovirus (38.5%) was the most commonly reported co-infection. No difference was observed between the two groups regarding the 30-day mortality (HR 0.39, 95% CI 0.13, 1.20; p = 0.10). The in-hospital mortality was significantly lower among co-infected patients with other respiratory viruses compared with patients who were infected with COVID-19 alone (HR 0.32 95% CI 0.10, 0.97; p = 0.04). Patients concomitantly infected with other respiratory viruses had longer median mechanical ventilation (MV) duration and hospital length of stay (LOS). CONCLUSION: Critically ill patients with COVID-19 who were concomitantly infected with other respiratory viruses had comparable 30-day mortality to those not concomitantly infected. Further proactive testing and care may be required in the case of co-infection with respiratory viruses and COVID-19. The results of our study need to be confirmed by larger studies.

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.

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.

Therapeutic Plasma Exchange and Supratherapeutic Levels of Unfractionated Heparin in the Management of Critically Ill Patient with Myasthenia Gravis: A Case Report.

BACKGROUND Therapeutic plasma exchange (TPE) is an extracorporeal method of filtration indicated in several conditions, including myasthenia gravis (MG). The removal and replacement of plasma through TPE affect the level of coagulation factors, suggesting alterations in homeostasis. TPE also has the potential to remove medications from the plasma. Insufficient data are available that evaluate the effect of TPE on certain medications, such as unfractionated heparin (UFH). CASE REPORT We report a case of a 78-year-old woman with MG. She underwent a thymectomy complicated by phrenic nerve injury and respiratory failure, requiring admission to the Intensive Care Unit (ICU) and mechanical ventilation. She developed a provoked left upper extremity deep venous thrombosis and started on therapeutic UFH with a target activated partial thromboplastin time (aPTT) of 50 to 80 seconds. Despite being on immunosuppressants, additional therapy with TPE was deemed necessary for her MG exacerbation. Therefore, she received 5 sessions of TPE, given every other day. Interestingly, while on TPE therapy, the aPTT increased significantly after each administration, with TPE reaching >170 seconds in some instances. As a precautionary measure, heparin infusion was held for 1 day based on the institutional heparin protocol and the physician's decision. Fortunately, the patient did not develop any bleeding complications. CONCLUSIONS TPE treatment may temporarily deplete the coagulation factors, leading to supratherapeutic aPTT levels. UFH dose adjustment and frequent assessment of aPTT levels are essential during TPE treatment to minimize serious bleeding complications. Future studies with a larger sample size are required to focus on understanding the effect of TPE on medications.

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.

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.

Statins and Risk of Thrombosis in Critically ill Patients with COVID-19: A Multicenter Cohort Study.

PURPOSE: Coagulation abnormalities are one of the most important complications of severe COVID-19, which might lead to venous thromboembolism (VTE). Hypercoagulability with hyperfibrinogenemia causes large vessel thrombosis and major thromboembolic sequelae. Statins are potentially a potent adjuvant therapy in COVID-19 infection due to their pleiotropic effect. This study aims to evaluate the effectiveness of statins in reducing the risk of thrombosis among hospitalized critically ill patients with COVID-19. METHODS: 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 categorized based on their usage of statins throughout their ICU stay and were matched with a propensity score. The primary endpoint was the odds of all cases of thrombosis; other outcomes were considered secondary. RESULTS: A total of 1039 patients were eligible; following propensity score matching, 396 patients were included (1:1 ratio). The odds of all thrombosis cases and VTE events did not differ significantly between the two groups (OR 0.84 (95% CI 0.43, 1.66), P = 0.62 and OR 1.13 (95% CI 0.43, 2.98), P = 0.81, respectively. On multivariable Cox proportional hazards regression analysis, patients who received statin therapy had lower 30-day (HR 0.72 (95 % CI 0.54, 0.97), P = 0.03) and in-hospital mortality (HR 0.67 (95 % CI 0.51, 0.89), P = 0.007). Other secondary outcomes were not statistically significant between the two groups except for D-dimer levels (peak) during ICU stay. CONCLUSION: The use of statin therapy during ICU stay was not associated with thrombosis reduction in critically ill patients with COVID-19; however, it has been associated with survival benefits.

Evaluation of Apixaban safety and effectiveness in morbidly obese patients with atrial fibrillation: a retrospective cohort study.

BACKGROUND: The benefit of apixaban to reduce stroke risk in morbidly obese patients with nonvalvular atrial fibrillation (AF) is still undetermined. The International Society of Thrombosis and Hemostasis recommends avoiding the use of direct oral anticoagulants (DOAC)s in morbidly obese patients (body mass index > 40 or weight > 120 kg) because of limited clinical data. This exploratory study aims to evaluate the effectiveness and safety of using apixaban in morbidly obese (body mass index (BMI) ≥ 40) patients with AF. METHODS: An exploratory retrospective cohort study was conducted at a single-center, including adult patients with non-valvular AF using apixaban between 01/01/2016 and 31/12/2019. Patients were excluded if they were known to have liver cirrhosis Child-Pugh C, mechanical valve, serum creatinine > 1.5 mg/dL, follow up < 3 months, or using apixaban with a dose of ≤5 or > 10 mg/day. Included patients were categorized into two groups based on their BMI (BMI<40 Vs. BMI ≥ 40). The primary outcome was all thrombotic events, while the secondary outcomes were major and minor bleeding after apixaban initiation. Propensity score (PS) matching was used (1:1 ratio) based on the patient's age, gender, and HAS-BLED score. RESULTS: A total of 722 patients were eligible; 254 patients were included after propensity score matching based on the selected criteria. The prevalence of all thrombotic events was similar between the two groups in the first year of apixaban initiation (OR (95%CI): 0.58 (0.13, 2.5), p-value = 0.46). In addition, the odds of developing major and minor bleeding were not statistically significant between the two groups (OR (95%CI): 0.39 (0.07, 2.03), p-value = 0.26 and OR (95%CI): 1.27 (0.56, 2.84), p-value = 0.40), respectively). CONCLUSION: This exploratory study showed similar effectiveness and safety of apixaban use in both morbid and non-morbid obese patients with non-valvular AF. However, a larger randomized controlled trial with a longer follow-up period needs to confirm our findings.

The potential role of adjunctive ascorbic acid in the prevention of colistin-induced nephrotoxicity in critically ill patients: A retrospective study.

Background: Colistin is considered a valuable and last-resort therapeutic option for MDR gram-negative bacteria. Nephrotoxicity is the most clinically pertinent adverse effect of colistin. Vivo studies suggest that administering oxidative stress-reducing agents, such as ascorbic acid, is a promising strategy to overcome colistin-induced nephrotoxicity (CIN). However, limited clinical data explores the potential benefit of adjunctive ascorbic acid therapy for preventing CIN. Therefore, this study aims to assess the potential nephroprotective role of ascorbic acid as adjunctive therapy against CIN in critically ill patients. Method: This was a retrospective cohort study at King Abdulaziz Medical City (KAMC) for all critically ill adult patients who received IV colistin. Eligible patients were classified into two groups based on the ascorbic acid use as concomitant therapy within three days of colistin initiation. The primary outcome was CIN odds after colistin initiation, while the secondary outcomes were 30-day mortality, in-hospital mortality, ICU, and hospital LOS. Propensity score (PS) matching was used (1:1 ratio) based on the patient's age, SOFA score, and serum creatinine. Results: A total of 451 patients were screened for eligibility; 90 patients were included after propensity score matching based on the selected criteria. The odds of developing CIN after colistin initiation were similar between patients who received ascorbic acid (AA) as adjunctive therapy compared to patients who did not (OR (95 %CI): 0.83 (0.33, 2.10), p-value = 0.68). In addition, the 30-day mortality, in-hospital mortality, ICU, and hospital LOS were similar between the two groups. Conclusion: Adjunctive use of Ascorbic acid during colistin therapy was not associated with lower odds of CIN. Further studies with a larger sample size are required to confirm these findings.