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

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

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

BackgroundDespite 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.MethodsA 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.ResultsA 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].ConclusionThe 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

Cardiovascular adverse events of antineoplastic monoclonal antibodies among cancer patients: real-world evidence from a tertiary healthcare system

Abstract Background Antineoplastic monoclonal antibodies (mAbs), such as trastuzumab, bevacizumab, and pertuzumab have been the mainstay of therapy in cancer patients. Despite proven efficacy of the monoclonal antibodies, cardiovascular-induced adverse events such as heart failure, hypertension, ischemic heart disease, arrhythmias, thromboembolic events, and hemorrhage remain a major complication. The European society of cardiology address that concern with antineoplastic monoclonal antibodies issuing a guideline to manage and monitor chemotherapy-induced cardiotoxicity. There is limited evidence of the real-world prevalence of cardiovascular (CV) events induced by monoclonal antibodies among patients with cancer in Saudi Arabia. Objective To evaluate the prevalence of cardiovascular adverse events among patients with cancer treated with monoclonal antibodies in Saudi Arabia. Methods This is a retrospective study conducted in a tertiary care hospital, Riyadh, Saudi Arabia. Data were obtained from an electronic medical record of patients with cancer treated with one of the selected monoclonal antibodies, who met the inclusion criteria between January 2005 until June 2015 and have been followed up for at least one year. Patients were stratified into groups according to monoclonal antibodies treatment: trastuzumab, bevacizumab, pertuzumab, and combined mAbs. Results A total of 1067 patient were included in the study, within the pre-determined study period. The prevalence of cardiovascular disease among patients with cancer treated with monoclonal antibodies was 16.3%. The prevalence of heart failure was relatively higher in the trastuzumab group (46/626 patients, 7.3%). Among 418 patients treated with bevacizumab, hypertension was the most frequent adverse event, reported in 38 patients (9.1%), followed by thromboembolism reported in 27 patients (6.5%). Treatment discontinuation owing to cardiovascular adverse events was reported in 42/1,067 patients (3.9%). Conclusion and relevance Prevalence of antineoplastic monoclonal antibody induced cardiovascular adverse events among patients with cancer is substantially high in Saudi Arabia. There is an urgent need to streamline the practice for identifying high risk patients and flexible referral system for cardio-oncology care

Comparative Effectiveness of Apixaban and Rivaroxaban Lead-in Dosing in VTE Treatment: Observational Multicenter Real-World Study

Apixaban and rivaroxaban require lead-in dosing for 7 and 21 days, respectively, when treating venous thromboembolism (VTE). However, no evidence exists to support subtracting parenteral anticoagulation days from total lead-in dosing. A multicenter study was conducted, including adult patients with acute VTE who received apixaban or rivaroxaban. The patients were grouped as follows. The recommended group received oral lead-in anticoagulant for the full recommended duration. The mixed group received lead-in therapy as parenteral with oral anticoagulant. The incidence of recurrent VTE (rVTE) and major bleeding (MB) within 90 days were the main outcomes. Of the 368 included patients, 47.8% received apixaban, and 52.2% received rivaroxaban. The recommended lead-in was used in 296 patients (80.4%), whereas 72 (19.6%) received the mixed-lead-in regimen. Five patients had rVTE events within 90 days; two occurred during hospitalization in the recommended group versus none in the mixed group (0.7% vs. 0.0%; p = 1.000). After discharge, two events occurred in the recommended group and one in the mixed group (0.7% vs. 1.4%; p = 0.481). In terms of MB, 24 events occurred in 21 patients within 90 days. During hospitalization, 11 events occurred in the recommended group and seven in the mixed group (3.7% vs. 9.7%; p = 0.060). After discharge, five more events occurred in the recommended group and one in the mixed group (1.4% vs. 1.7%; p = 1.000). The mixed-lead-in regimen is safe and effective in comparison with the recommended-lead-in regimen

Evaluation of the Safety and Effectiveness of Topical Intrapleural Application of Tranexamic Acid in Thoracic Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objectives Bleeding remains a common complication post-thoracic surgery. Although intravenous tranexamic acid (TXA) has been shown to decrease blood loss, its use has been associated with adverse effects. Accordingly, topical TXA has been proposed as an alternative to reduce bleeding with fewer systemic complications. Methods We searched Medline, Embase, and Cochrane Central databases for randomized controlled trials (RCTs) comparing topical TXA versus control (i.e., placebo) in patients undergoing thoracic procedures. The primary outcome was total postoperative blood loss at 24 hours. Secondary outcomes included were the number of red blood cell (RBC) transfusions, and hospital length of stay (LOS). Meta-analyses were pooled using mean difference with inverse-variance weighting and random-effects. Results Out of the 575 unique studies that were screened, we identified three randomized controlled trials (RCTs) involving 399 patients. Out of the three RCTs analyzed, two studies, accounting for 67% of the total, were found to have a low risk of bias. The primary outcome of 24-h post-operative blood loss was significantly lower in patients who received TXA (mean difference [MD] −93.6 ml, 95% CI −121.8 to −65.4 ml, I 2  = 45%). In addition, the need for RBC transfusion was significantly lower in the topical TXA group compared to control (MD −0.5 units, 95% CI −0.8 to −0.3 units, I 2  = 60%). However, there was no significant difference in the hospital length of stay (LOS) (MD −0.3 days, 95% CI −0.9 to 0.4 days, I 2  = 0%). These results remained consistent after several sensitivity analyses. The use of topical intrapleural tranexamic acid has also been found to be safe without any significant safety concerns. Conclusion Topical intrapleural TXA reduces blood loss and the need for blood transfusions during thoracic surgery. In addition, there is no evidence of the increased safety concerns associated with its use. Larger trials are necessary to validate these findings and evaluate the safety and efficacy of different dosages

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

Abstract 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

Additional file 1 of Dexamethasone versus methylprednisolone for multiple organ dysfunction in COVID-19 critically ill patients: a multicenter propensity score matching study

Additional file 1. Outcome definition (s)