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.

The association between tocilizumab therapy and the development of thrombosis in critically ill patients with COVID-19: a multicenter, cohort study.

The use of tocilizumab for the management of COVID-19 emerged since it modulates inflammatory markers by blocking interleukin 6 receptors. Concerns regarding higher thrombosis risk while using tocilizumab were raised in the literature. The aim of this study is to investigate the association between tocilizumab therapy and the development of thromboembolic events in critically ill COVID-19 patients. A propensity score-matched, multicenter cohort study for critically ill adult patients with COVID-19. Eligible patients admitted to ICU between March 2020 and July 2021 were categorized into two sub-cohorts based on tocilizumab use within 24 h of ICU admission. The primary endpoint was to assess the incidence of all thrombosis cases during ICU stay. The secondary endpoints were 30-day mortality, in-hospital mortality, and the highest coagulation parameters follow-up (i.e., D-dimer, Fibrinogen) during the stay. Propensity score matching (1:2 ratio) was based on nine matching covariates. Among a total of 867 eligible patients, 453 patients were matched (1:2 ratio) using propensity scores. The thrombosis events were not statistically different between the two groups in crude analysis (6.8% vs. 7.7%; p-value = 0.71) and regression analysis [OR 0.83, 95% CI (0.385, 1.786)]. Peak D-dimer levels did not change significantly when the patient received tocilizumab (beta coefficient (95% CI): 0.19 (- 0.08, 0.47)), while there was a significant reduction in fibrinogen levels during ICU stay (beta coefficient (95% CI): - 0.15 (- 0.28, - 0.02)). On the other hand, the 30-day and in-hospital mortality were significantly lower in tocilizumab-treated patients (HR 0.57, 95% CI (0.37, 0.87), [HR 0.67, 95% CI (0.46, 0.98), respectively). The use of tocilizumab in critically ill patients with COVID-19 was not associated with higher thrombosis events or peak D-dimer levels. On the other hand, fibrinogen levels, 30-day and in-hospital mortality were significantly lower in the tocilizumab group. Further randomized controlled trials are needed to confirm our findings.

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.

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 Impact of Midodrine Tapering Versus Nontapering Regimens on the Clinical Outcomes of Critically Ill Patients: A Retrospective Cohort Study.

BACKGROUND: Midodrine has been used in the intensive care unit (ICU) setting to reduce the time to vasopressor discontinuation. The limited data supporting midodrine use have led to variability in the pattern of initiation and discontinuation of midodrine. OBJECTIVES: To compare the effectiveness and safety of 2 midodrine discontinuation regimens during weaning vasopressors in critically ill patients. METHODS: A retrospective cohort study was conducted at King Abdulaziz Medical City. Included patients were adults admitted to ICU who received midodrine after being unable to be weaned from intravenous vasopressors for more than 24 hours. Patients were categorized into two subgroups depending on the pattern of midodrine discontinuation (tapered dosing regimen vs. nontapered regimen). The primary endpoint was the incidence of inotropes and vasopressors re-initiation after midodrine discontinuation. RESULTS: The incidence of inotropes or vasopressors' re-initiation after discontinuation of midodrine was lower in the tapering group (15.4%) compared with the non-tapering group (40.7%) in the crude analysis as well as regression analysis (odd ratio [OR] = 0.15; 95% CI = 0.03, 0.73, P = 0.02). The time required for the antihypertensive medication(s) initiation after midodrine discontinuation was longer in patients who had dose tapering (beta coefficient (95% CI): 3.11 (0.95, 5.28), P = 0.005). Moreover, inotrope or vasopressor requirement was lower 24 hours post midodrine initiation. In contrast, the two groups had no statistically significant differences in 30-day mortality, in-hospital mortality, or ICU length of stay. CONCLUSION AND RELEVANCE: These real-life data showed that tapering midodrine dosage before discontinuation in critically ill patients during weaning from vasopressor aids in reducing the frequency of inotrope or vasopressor re-initiation. Application of such a strategy might be a reasonable approach among ICU patients unless contraindicated.

Atomized Intranasal Ketorolac Versus Intravenous Ketorolac for the Treatment of Severe Renal Colic in the Emergency Department: A Double-Blind, Randomized Controlled Trial.

STUDY OBJECTIVE: Atomized intranasal (IN) drug administration offers an alternative to the intravenous (IV) route. We aimed to evaluate the analgesic efficacy of IN versus IV ketorolac in emergency department patients with acute renal colic. METHODS: We conducted a double-blind, randomized controlled trial on adult patients (aged 18 to 64 years) with severe renal colic and numerical rating scale pain ratings ≥7.0. They were randomly assigned (1:1) to receive single doses of either IN or IV ketorolac. Our main outcomes were differences in numerical rating scale reduction at 30 and 60 minutes. A 95% confidence interval (CI) was calculated for each mean difference, with a minimum clinically important difference set at 1.3 points. Secondary outcomes included treatment response, adverse events, rescue medications, and emergency department revisits. We analyzed using intention-to-treat. RESULTS: A total of 86 and 85 patients with similar baseline characteristics were allocated to the IV and IN groups, respectively. Mean numerical rating scale scores were 8.52 and 8.65 at baseline, 3.85 and 4.67 at 30 minutes, and 2.80 and 3.04 at 90 minutes, respectively. The mean numerical rating scale reduction differences between the IV and IN groups were 0.69 (95% CI -0.08 to 1.48) at 30 minutes and 0.10 (95% CI -0.85 to 1.04) at 60 minutes. There were no differences in secondary outcomes. CONCLUSION: Neither IN or IV ketorolac was superior to the other for the treatment of acute renal colic, and both provided clinically meaningful reductions in pain scores at 30 to 60 minutes.

The Impact of Recombinant Human Erythropoietin Administration in Critically ill COVID-19 Patients: A Multicenter Cohort Study.

The use of erythropoietin-stimulating agents (ESAs) as adjunctive therapy in critically ill patients with COVID-19 may have a potential benefit. This study aims to evaluate the effect of ESAs on the clinical outcomes of critically ill COVID-19 patients. A multicenter, retrospective cohort study was conducted from 01-03-2020 to 31-07-2021. We included adult patients who were ≥ 18 years old with a confirmed diagnosis of COVID-19 infection and admitted to intensive care units (ICUs). Patients were categorized depending on ESAs administration during their ICU stay. The primary endpoint was the length of stay; other endpoints were considered secondary. After propensity score matching (1:3), the overall included patients were 120. Among those, 30 patients received ESAs. A longer duration of ICU and hospital stay was observed in the ESA group (beta coefficient: 0.64; 95% CI: 0.31-0.97; P = < .01, beta coefficient: 0.41; 95% CI: 0.12-0.69; P = < .01, respectively). In addition, the ESA group's ventilator-free days (VFDs) were significantly shorter than the control group. Moreover, patients who received ESAs have higher odds of liver injury and infections during ICU stay than the control group. The use of ESAs in COVID-19 critically ill patients was associated with longer hospital and ICU stays, with no survival benefits but linked with lower VFDs.

Clonidine safety and effectiveness in the management of suspected paroxysmal sympathetic hyperactivity post-traumatic brain injury: A retrospective cohort study.

INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. In addition, TBI may cause paroxysmal sympathetic hyperactivity (PSH), which is associated with poor clinical outcomes. This study aimed to evaluate the safety and effectiveness of clonidine in patients with TBI and suspected PSH. METHODS: A retrospective cohort study for critically ill patients with TBI with suspected PSH admitted to intensive care units (ICUs) from 1 May 2016 to 31 January 2020 at a tertiary academic medical center. Eligible patients were categorized based on clonidine use during their ICU stay (Clonidine group vs. Control group). The primary outcome was the improvement in functional outcomes during ICU stay, defined by a delta Glasgow Coma Score (GCS). Secondary outcomes included ICU and hospital length of stay, heart rate variation, and 90-day mortality. RESULTS: A total of 2915 patients were screened, of which 169 were included. Based on multiple regression analysis, patients who received clonidine showed better improvement in functional outcomes by a higher mean delta GCS than patients who did not (Beta Coeff. 0.41; CI: 0.07 - 0.74; P = 0.02). In addition, the patient's GCS upon ICU discharge and IV opioids requirement on day three were higher in the clonidine group than control (beta coefficient (95% CI): 0.18 (0.03, 0.32); p = 0.02 and beta coefficient (95% CI): 1.38 (0.24, 2.52); p = 0.02, respectively). No statistical differences were observed in any of the other secondary outcomes after adjusting for confounders. CONCLUSION: This study found that patients who received clonidine had better functional outcomes during their ICU stay, as shown by their delta GCS than those who did not. Other outcomes were similar between the groups. More data are needed to explore the role of clonidine in patients with TBI with suspected PSH.

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.

Synthesis of functionalized alkenes via Cu(I)-catalysed allylation of acetanilides using Morita-Baylis-Hillman bromides.

An easy access to functionalized alkenes has been developed by the C-H functionalization of anilides with Morita-Baylis-Hillman (MBH) bromides in the presence of copper chloride, TBHP and acetic acid. Unsubstituted as well as ortho/meta-substituted anilides exclusively give rise to the para-allylated products, whereas para-substitution brings about the formation of ortho-allylated anilides.

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.

Diagnosing and managing heat exhaustion: insights from a systematic review of cases in the desert climate of Mecca.

Heat exhaustion (HE) is a common, yet obscure, heat-related illness that affects millions of people yearly and its burden is projected to rise due to climate change. A comprehensive literature synthesis is lacking despite previous studies on various HE aspects. This systematic review aims to fill this gap by identifying and synthesizing available evidence on the risk factors, symptoms, biomarkers, treatment options, and outcomes for HE. The review focused on HE during the Muslim (Hajj) pilgrimage where the condition is endemic. We conducted a structured search of MEDLINE/PubMed, Embase, Web of Science Core Collection, SCOPUS, and CINAHL databases. We summarized the data from eligible studies and synthesized them in narrative form using pooled descriptive statistics. Ten studies were included between 1980 and 2019, reporting over 1,194 HE cases. HE cases presented with elevated core temperature (up to 40°C) and mainly affected older males from the Middle East and North Africa region, with overweight individuals at a higher risk. Clinical symptoms included hyperventilation, fatigue, dizziness, headaches, nausea, and vomiting, but not central nervous system disturbances. HE was associated with cardiac stress, and with water, electrolyte, and acid-base alterations. Cooling and hydration therapy were the primary management strategies, leading to a low mortality rate (pooled case fatality rate=0.11 % [95 % CI: 0.01, 0.3]). Most cases recovered within a few hours without complications. HE is associated with cardiac stress and changes in homeostasis, leading to distinct clinical symptoms. Early diagnosis and treatment of HE are crucial in reducing the risk of complications and mortality. The review provides insights into the pathophysiology and outcomes of HE, adding to the scarce literature on the subject. Prospero registration number: CRD42022325759.

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.

Impact of Ursodeoxycholic Acid in Critically Ill Patients With Sepsis: A Retrospective Study.

Background: Using ursodeoxycholic acid (UDCA) in critically ill patients as adjunctive therapy for sepsis/septic shock in neonates and children is controversial, while it has not been extensively investigated in adults. This study aims to assess the effect of UDCA use on the early resolution of sepsis/septic shock in critically ill adult patients. Method: A retrospective study of critically ill adult patients in the intensive care unit (ICU) admitted with sepsis/septic shock at King Abdulaziz Medical City. Based on their usage of UDCA, patients were categorized into two groups. A total of 88 patients were included for analysis after matching, based on severity of illness scores within 24-hours of ICU admission. The primary outcome was to assess the effect of UDCA on the severity and resolution of shock at day three of ICU admission. The secondary outcomes were 30-day in-hospital mortality, mechanical ventilation (MV) duration, and ICU length of stay (LOS). Results: Out of the 88 patients matched, 44 patients (50%) received UDCA during the study period. Using UDCA was neither associated with improvement in Sequential Organ Failure Assessment (SOFA) score (p-value: 0.32), inotropes/vasopressors requirement (p-value: 0.79), Glasgow Coma Scale (GCS) (p-value: 0.59) nor total bilirubin levels (p-value: 0.79) at day three compared with the control. There was a significant association between using UDCA and improvement in PaO2/FiO2 ratio (p-value: 0.01) and early extubation at day three (p-value: 0.04). Conclusion: Using UDCA in critically ill patients with sepsis/septic shock was not associated with improvement in shock severity and resolution. However, patients who received UDCA were more likely to be extubated and not require MV on day three of ICU admission.

Classic heat stroke in a desert climate: A systematic review of 2632 cases.

BACKGROUND: Although classic heat stroke (HS) is one of the most ancient conditions known to humans, the description of its early clinical manifestations, natural course, and complications remains uncertain. OBJECTIVES: A systematic review of the demographics, clinical characteristics, biomarkers, therapy, and outcomes of HS during the Muslim (Hajj) pilgrimage in the desert climate of Mecca, Saudi Arabia. METHODS: We searched the MEDLINE, Embase, Web of Science Core Collection, SCOPUS, and CINAHL databases from inception to April 2022. We summarized the data from eligible studies and synthesized them in narrative form using pooled descriptive statistics. RESULTS: Forty-four studies, including 2632 patients with HS, met the inclusion criteria. Overweight or obesity, diabetes, and cardiovascular disease were prevalent among cases of HS. Evidence suggests that extreme hyperthermia (pooled mean = 42.0°C [95% confidence interval (CI): 41.9, 42.1], range 40-44.8°C) with hot and dry skin (>99% of cases) and severe loss of consciousness (mean Glasgow Coma Scale <8 in 53.8% of cases) were the dominant clinical characteristics of classic HS. Hypotension, tachypnea, vomiting, diarrhea, and biochemical biomarkers indicating mild-to-moderate rhabdomyolysis, acute kidney, liver, heart injury, and coagulopathy were frequent at the onset. Concomitantly, stress hormones (cortisol and catecholamines) and biomarkers of systemic inflammation and coagulation activation were increased. HS was fatal in 1 in 18 cases (pooled case fatality rate = 5.6% [95%CI: 4.6, 6.5]). CONCLUSIONS: The findings of this review suggest that HS induces an early multiorgan injury that can progress rapidly to organ failure, culminating in death, if it is not recognized and treated promptly.

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.