Optic Nerve Sheath Diameter Ultrasound for Raised Intracranial Pressure: A Literature Review and Meta-analysis of its Diagnostic Accuracy.

Optic nerve sheath diameter (ONSD) ultrasound is becoming increasingly more popular for estimating raised intracranial pressure (ICP). We performed a systematic review and analysis of the diagnostic accuracy of ONSD when compared to the standard invasive ICP measurement. METHOD: We performed a systematic search of PUBMED and EMBASE for studies including adult patients with suspected elevated ICP and comparing sonographic ONSD measurement to a standard invasive method. Quality of studies was assessed using the QUADAS-2 tool by two independent authors. We used a bivariate model of random effects to summarize pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Heterogeneity was investigated by meta-regression and sub-group analyses. RESULTS: We included 18 prospective studies (16 studies including 619 patients for primary outcome). Only one study was of low quality, and there was no apparent publication bias. Pooled sensitivity was 0.9 [95% confidence intervals (CI): 0.85-0.94], specificity was 0.85 (95% CI: 0.8-0.89), and DOR was 46.7 (95% CI: 26.2-83.2) with partial evidence of heterogeneity. The Area-Under-the-Curve of the summary Receiver-Operator-Curve was 0.93 (95% CI: 0.91-0.95, P < .05). No covariates were significant in the meta-regression. Subgroup analysis of severe traumatic brain injury and parenchymal ICP found no heterogeneity. ICP and ONSD had a correlation coefficient of 0.7 (95% CI: 0.63-0.76, P < .05). CONCLUSION: ONSD is a useful adjunct in ICP evaluation but is currently not a replacement for invasive methods where they are feasible.

Continuous renal replacement therapy with the addition of CytoSorb cartridge in critically ill patients with COVID-19 plus acute kidney injury: A case-series.

Our aim was to investigate continuous renal replacement therapy (CRRT) with CytoSorb cartridge for patients with life-threatening COVID-19 plus acute kidney injury (AKI), sepsis, acute respiratory distress syndrome (ARDS), and cytokine release syndrome (CRS). Of 492 COVID-19 patients admitted to our intensive care unit (ICU), 50 had AKI necessitating CRRT (10.16%) and were enrolled in the study. Upon ICU admission, all had AKI, ARDS, septic shock, and CRS. In addition to CRRT with CytoSorb, all received ARDS-net ventilation, prone positioning, plus empiric ribavirin, interferon beta-1b, antibiotics, hydrocortisone, and prophylactic anticoagulation. We retrospectively analyzed inflammatory biomarkers, oxygenation, organ function, duration of mechanical ventilation, ICU length-of-stay, and mortality on day-28 post-ICU admission. Patients were 49.64 ± 8.90 years old (78% male) with body mass index of 26.70 ± 2.76 kg/m2 . On ICU admission, mean Acute Physiology and Chronic Health Evaluation (APACHE) II was 22.52 ± 1.1. Sequential Organ Function Assessment (SOFA) score was 9.36 ± 2.068 and the ratio of partial arterial pressure of oxygen to fractional inspired concentration of oxygen (PaO2 /FiO2 ) was 117.46 ± 36.92. Duration of mechanical ventilation was 17.38 ± 7.39 days, ICU length-of-stay was 20.70 ± 8.83 days, and mortality 28 days post-ICU admission was 30%. Nonsurvivors had higher levels of inflammatory biomarkers, and more unresolved shock, ARDS, AKI, and pulmonary emboli (8% vs. 4%, P < .05) compared to survivors. After 2 ± 1 CRRT sessions with CytoSorb, survivors had decreased SOFA scores, lactate dehydrogenase, ferritin, D-dimers, C-reactive protein, and interleukin-6; and increased PaO2 /FiO2 ratios, and lymphocyte counts (all P < .05). Receiver-operator-curve analysis showed that posttherapy values of interleukin-6 (cutoff point >620 pg/mL) predicted in-hospital mortality for critically ill COVID-19 patients (area-under-the-curve: 0.87, 95% CI: 0.81-0.93; P = .001). No side effects of therapy were recorded. In this retrospective case-series, CRRT with the CytoSorb cartridge provided a safe rescue therapy in life-threatening COVID-19 with associated AKI, ARDS, sepsis, and hyperinflammation.

Thrombolysis in severe COVID-19 pneumonia with massive pulmonary embolism.

OBJECTIVE: No guidelines exist for the management of massive pulmonary embolism (PE) in COVID-19. We present a COVID-19 patient with refractory acute respiratory syndrome (ARDS), and life-threatening PE who underwent successful thrombolysis. CASE PRESENTATION: A previously healthy 47 year old male was admitted to our hospital due to severe COVID-19 pneumonia [confirmed by Real-Time-Polymerase-Chain-Reaction (RT-PCR)]. He had rapidly evolving ARDS [partial arterial pressure of oxygen to fractional inspired concentration of oxygen ratio: 175], and sepsis. Laboratory results showed lymphocytopenia, and increased D-dimer levels (7.7 µg/ml; normal: 0-0.5 µg/ml). The patient was treated in the intensive care unit. On day-1, ARDS-net/prone positioning ventilation, and empiric anti-COVID treatment integrating prophylactic anticoagulation was administered. On hospital day-2, the patient developed shock with worsening oxygenation. Point-of-care-ultrasound depicted a large thrombus migrating from the right atrium to the pulmonary circulation. Intravenous alteplase (100 mg over 2 h) was administered as rescue therapy. The patient made an uneventful recovery, and was discharged to home isolation (day-20) on oral rivaroxaban. CONCLUSION: Thrombolysis may have a critical therapeutic role for massive PE in COVID-19; however the risk of potential bleeding should not be underestimated. Point-of-care ultrasound has a pivotal role in the management of refractory ARDS in COVID-19.

Prospective Longitudinal Evaluation of Point-of-Care Lung Ultrasound in Critically Ill Patients With Severe COVID-19 Pneumonia.

OBJECTIVES: To perform a prospective longitudinal analysis of lung ultrasound findings in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: Eighty-nine intensive care unit (ICU) patients with confirmed COVID-19 were prospectively enrolled and tracked. Point-of-care ultrasound (POCUS) examinations were performed with phased array, convex, and linear transducers using portable machines. The thorax was scanned in 12 lung areas: anterior, lateral, and posterior (superior/inferior) bilaterally. Lower limbs were scanned for deep venous thrombosis and chest computed tomographic angiography was performed to exclude suspected pulmonary embolism (PE). Follow-up POCUS was performed weekly and before hospital discharge. RESULTS: Patients were predominantly male (84.2%), with a median age of 43 years. The median duration of mechanical ventilation was 17 (interquartile range, 10-22) days; the ICU length of stay was 22 (interquartile range, 20.2-25.2) days; and the 28-day mortality rate was 28.1%. On ICU admission, POCUS detected bilateral irregular pleural lines (78.6%) with accompanying confluent and separate B-lines (100%), variable consolidations (61.7%), and pleural and cardiac effusions (22.4% and 13.4%, respectively). These findings appeared to signify a late stage of COVID-19 pneumonia. Deep venous thrombosis was identified in 16.8% of patients, whereas chest computed tomographic angiography confirmed PE in 24.7% of patients. Five to six weeks after ICU admission, follow-up POCUS examinations detected significantly lower rates (P < .05) of lung abnormalities in survivors. CONCLUSIONS: Point-of-care ultrasound depicted B-lines, pleural line irregularities, and variable consolidations. Lung ultrasound findings were significantly decreased by ICU discharge, suggesting persistent but slow resolution of at least some COVID-19 lung lesions. Although POCUS identified deep venous thrombosis in less than 20% of patients at the bedside, nearly one-fourth of all patients were found to have computed tomography-proven PE.

Residual Lung Injury in Patients Recovering From COVID-19 Critical Illness: A Prospective Longitudinal Point-of-Care Lung Ultrasound Study.

Scarce data exist regarding the natural history of lung lesions detected on ultrasound in those who survive severe COVID-19 pneumonia. OBJECTIVE: We performed a prospective analysis of point-of-care ultrasound (POCUS) findings in critically ill COVID-19 patients during and after hospitalization. METHODS: We enrolled 171 COVID-19 intensive care unit patients. POCUS of the lungs was performed with phased array (2-4 MHz), convex (2-6 MHz) and linear (10-15 MHz) transducers, scanning 12 lung areas. Chest computed tomography angiography was performed to exclude suspected pulmonary embolism. Survivors were clinically and sonographically evaluated during a 4 month period for evidence of residual lung injury. Chest computed tomography angiography and echocardiography were used to exclude pulmonary hypertension (PH) and chest high-resolution-computed-tomography to exclude interstitial lung disease (ILD) in symptomatic survivors. RESULTS: Cox regression analysis showed that lymphocytopenia (hazard ratio [HR]: 0.88, 95% confidence intervals [CI]: 0.68-0.96, p = .048), increased lactate (HR: 1.17, 95% CI: 0.94-1.46, p = 0.049), and D-dimers (HR: 1.21, 95% CI: 1.03-1.44, p = .03) were mortality predictors. Non-survivors had increased incidence of pulmonary abnormalities (B-lines, pleural line irregularities, and consolidations) compared to survivors (p < .05). During follow-up, POCUS with clinical and laboratory parameters integrated in the semi-quantitative Riyadh-Residual-Lung-Injury scale had sensitivity of 0.82 (95% CI: 0.76-0.89) and specificity of 0.91 (95% CI: 0.94-0.95) in predicting ILD. The prevalence of PH and ILD (non-specific-interstitial-pneumonia) was 7% and 11.8%, respectively. CONCLUSION: POCUS showed ability to monitor the evolution of severe COVID-19 pneumonia after hospital discharge, supporting its integration in clinical predictive models of residual lung injury.

Reverse takotsubo cardiomyopathy in fulminant COVID-19 associated with cytokine release syndrome and resolution following therapeutic plasma exchange: a case-report.

BACKGROUND: Fulminant (life-threatening) COVID-19 can be associated with acute respiratory failure (ARF), multi-system organ failure and cytokine release syndrome (CRS). We present a rare case of fulminant COVID-19 associated with reverse-takotsubo-cardiomyopathy (RTCC) that improved with therapeutic plasma exchange (TPE). CASE PRESENTATION: A 40 year old previous healthy male presented in the emergency room with 4 days of dry cough, chest pain, myalgias and fatigue. He progressed to ARF requiring high-flow-nasal-cannula (flow: 60 L/minute, fraction of inspired oxygen: 40%). Real-Time-Polymerase-Chain-Reaction (RT-PCR) assay confirmed COVID-19 and chest X-ray showed interstitial infiltrates. Biochemistry suggested CRS: increased C-reactive protein, lactate dehydrogenase, ferritin and interleukin-6. Renal function was normal but lactate levels were elevated. Electrocardiogram demonstrated non-specific changes and troponin-I levels were slightly elevated. Echocardiography revealed left ventricular (LV) basal and midventricular akinesia with apex sparing (LV ejection fraction: 30%) and depressed cardiac output (2.8 L/min) consistent with a rare variant of stress-related cardiomyopathy: RTCC. His ratio of partial arterial pressure of oxygen to fractional inspired concentration of oxygen was < 120. He was admitted to the intensive care unit (ICU) for mechanical ventilation and vasopressors, plus antivirals (lopinavir/ritonavir), and prophylactic anticoagulation. Infusion of milrinone failed to improve his cardiogenic shock (day-1). Thus, rescue TPE was performed using the Spectra Optia™ Apheresis System equipped with the Depuro D2000 Adsorption Cartridge (Terumo BCT Inc., USA) without protective antibodies. Over 5 days he received daily TPE (each lasting 4 hours). His lactate levels, oxygenation, and LV function normalized and he was weaned off vasopressors. His inflammation markers improved, and he was extubated on day-7. RT-PCR was negative on day-17. He was discharged to home isolation in good condition. CONCLUSION: Stress-cardiomyopathy may complicate the course of fulminant COVID-19 with associated CRS. If inotropic therapy fails, TPE without protective antibodies may help rescue the critically ill patient.

Examining the Effects of Social Media on Mental Health Among Adolescents in Saudi Arabia.

BACKGROUND: Adolescents are immersed in a highly advanced technology setting, characterized by extensive availability of personal devices, the internet, and other social media platforms, which greatly impact their mental development. Concerns arise around potential negative consequences, including social isolation, internet addiction, exposure to improper content, depression, cyberbullying, and sleeping difficulty. The impact of social media on the mental well-being of adolescents has emerged as an escalating concern. The continuous exposure to carefully selected content, online harassment, and the expectation to comply with unrealistic standards all contribute to the development of depression and anxiety. This research aims to explore the impact of social media on the mental health of adolescents in the Saudi Arabian context. METHODS: This online cross-sectional study was conducted on Saudis aged 10 to 24 years old who have social media accounts in Saudi Arabia between August and November 2023. Binary logistic regression analysis was conducted to identify factors that make the study participants more likely to be mentally affected by social media. RESULTS: A total of 2856 participants were involved in this study. The most commonly used social media platform by the study participants was Twitter (30.3%). The majority of the study participants (77.4%) reported that they have tried to reduce their social media usage for mental health reasons. The most commonly agreed-upon statements were that "they feel that excessive social media use has negatively affected their sleep patterns," "they often sleep late in the night because of social media usage," and "they check their social media account before they sleep in the night," accounting for 71.0%, 66.1%, and 58.3%, respectively. Overall, the study participants showed a low level of being mentally affected due to social media with a mean score of 7.8 (SD: 3.9) out of 21, which is equal to 37.1%. Older participants (aged 16-24 years) were more prone to be mentally affected due to social media compared to younger ones (aged 10-15 years; p < 0.05). On the other hand, participants who were married, had a middle school education level, or lived in the northern, western, or eastern regions were less likely to be mentally affected due to social media compared to others (p < 0.05). CONCLUSION: The study participants showed a low level of being mentally affected due to social media. Individuals in the 16-24 years age group show a higher susceptibility to mental impacts resulting from social media usage. The primary duty for reducing the potential negative effects of social media should not rest only on parents and caregivers. Advocating for the creation of technology-free zones and fostering in-person friendships among teens could be a beneficial approach that policymakers should support.

Knowledge, Attitudes, and Practice Patterns of Lung Cancer Screening Among Physicians in Saudi Arabia.

BACKGROUND: Lung cancer remains the primary cause of death connected to cancer on a worldwide scale. Obtaining a deep understanding of the knowledge, attitudes, and behavior patterns of doctors is essential for developing successful strategies to improve lung cancer screening. This study aims to identify the attitudes, beliefs, referral practices, and knowledge of lung cancer screening among physicians in Saudi Arabia. METHODS: An online survey was conducted from July to December 2023 to investigate the attitudes, beliefs, referral practices, and knowledge of lung cancer screening, and adherence to lung cancer screening recommendations among physicians in Saudi Arabia. Internal medicine, family medicine, and pulmonology physicians of all levels (consultants, senior registrars, and residents) who are currently practicing medicine in Saudi Arabia formed the study population. This study employed a previously developed questionnaire. Binary logistic regression analysis was employed to identify factors that indicate a better degree of knowledge and a positive attitude toward lung cancer screening. RESULTS: This study involved a total of 96 physicians. The study participants demonstrated a significant degree of understanding regarding lung cancer screening, with an average knowledge score of 5.8 (SD: 1.7) out of 8, equivalent to 72.5% of the highest possible score. The accuracy rate for knowledge items varied from 44.8% to 91.7%. The study participants had a moderately favorable attitude toward lung cancer screening, as shown by a mean attitude score of 14.4 (SD: 3.7) out of a maximum possible score of 30, which corresponds to 48.0% of the highest achievable score. Around 36.5% of the survey participants reported engaging in the practice of discussing the results of lung cancer screening with patients. The primary obstacles frequently cited were challenges in patient scheduling, insufficient time to discuss lung cancer screening during clinic appointments, and patient refusal, constituting 59.4%, 53.1%, and 53.1% of the identified barriers, respectively. Physicians in Saudi Arabia, particularly those employed in private hospitals, demonstrated a higher level of knowledge of lung cancer screening compared to others (p < 0.05). In contrast, individuals with 11-15 years of experience were shown to have a 78.0% lower likelihood of being educated about lung cancer screening compared to their counterparts (p < 0.05). CONCLUSION: The study's results indicate that there is a need for the development of specialized educational initiatives aimed at Saudi Arabian physicians, particularly those with 11 to 15 years of experience who exhibit a limited understanding of lung cancer screening. Utilizing programs that provide continuing medical education would aid in their education. There is a need to facilitate communication between physicians and patients. It is critical to address the identified issues, such as streamlining the appointment scheduling process and ensuring patients have sufficient time during clinic visits. Furthermore, it is critical for the success of nationwide screening initiatives to foster collaboration between the public and private healthcare sectors.

Public Awareness Regarding Corticosteroid Use and Side Effects: A Cross-Sectional Study in Riyadh, Saudi Arabia.

The administration of corticosteroids may have possible hazards, ranging from minor adverse medication reactions to more serious considerations. We aimed to assess levels of public awareness concerning corticosteroid use, side effects, and predictors of its use. A cross-sectional study was conducted online throughout the period of May to July 2023. The present investigation utilized a previously developed questionnaire tool. The study encompassed a cohort of 732 individuals. Upon inquiry regarding the adverse effects of corticosteroid treatment, the participants predominantly reported weight gain, skin alterations, and fluid retention leading to breathing difficulties, constituting 44.4%, 30.3%, and 27.7% of the responses, respectively. The prevailing adverse effects observed in individuals using corticosteroids were weight gain, alterations in mood, and changes in skin characteristics, which accounted for 38.1%, 25.7%, and 21.8% of reported cases, respectively. Individuals within the age range of 41-50 years and those who are currently not working show a higher propensity for utilizing corticosteroids in comparison to other demographic groups (p < 0.05). The level of general public knowledge about corticosteroids and the side effects connected with them in Saudi Arabia was adequate. Demographic factors, such as age, gender, and education, have an impact on the use of corticosteroids.

Tocilizumab Outcomes in Critically Ill COVID-19 Patients Admitted to the ICU and the Role of Non-Tocilizumab COVID-19-Specific Medical Therapeutics.

BACKGROUND: Tocilizumab is a monoclonal antibody proposed to manage cytokine release syndrome (CRS) associated with severe COVID-19. Previously published reports have shown that tocilizumab may improve the clinical outcomes of critically ill patients admitted to the ICU. However, no precise data about the role of other medical therapeutics concurrently used for COVID-19 on this outcome have been published. OBJECTIVES: We aimed to compare the overall outcome of critically ill COVID-19 patients admitted to the ICU who received tocilizumab with the outcome of matched patients who did not receive tocilizumab while controlling for other confounders, including medical therapeutics for critically ill patients admitted to ICUs. METHODS: A prospective, observational, multicenter cohort study was conducted among critically ill COVID-19 patients admitted to the ICU of 14 hospitals in Saudi Arabia between 1 March 2020, and October 31, 2020. Propensity-score matching was utilized to compare patients who received tocilizumab to patients who did not. In addition, the log-rank test was used to compare the 28 day hospital survival of patients who received tocilizumab with those who did not. Then, a multivariate logistic regression analysis of the matched groups was performed to evaluate the impact of the remaining concurrent medical therapeutics that could not be excluded via matching 28 day hospital survival rates. The primary outcome measure was patients' overall 28 day hospital survival, and the secondary outcomes were ICU length of stay and ICU survival to hospital discharge. RESULTS: A total of 1470 unmatched patients were included, of whom 426 received tocilizumab. The total number of propensity-matched patients was 1278. Overall, 28 day hospital survival revealed a significant difference between the unmatched non-tocilizumab group (586; 56.1%) and the tocilizumab group (269; 63.1%) (p-value = 0.016), and this difference increased even more in the propensity-matched analysis between the non-tocilizumab group (466.7; 54.6%) and the tocilizumab group (269; 63.1%) (p-value = 0.005). The matching model successfully matched the two groups' common medical therapeutics used to treat COVID-19. Two medical therapeutics remained significantly different, favoring the tocilizumab group. A multivariate logistic regression was performed for the 28 day hospital survival in the propensity-matched patients. It showed that neither steroids (OR: 1.07 (95% CI: 0.75-1.53)) (p = 0.697) nor favipiravir (OR: 1.08 (95% CI: 0.61-1.9)) (p = 0.799) remained as a predictor for an increase in 28 day survival. CONCLUSION: The tocilizumab treatment in critically ill COVID-19 patients admitted to the ICU improved the overall 28 day hospital survival, which might not be influenced by the concurrent use of other COVID-19 medical therapeutics, although further research is needed to confirm this.

Mortality and Pulmonary Embolism in Acute Respiratory Distress Syndrome From COVID-19 vs. Non-COVID-19.

Purpose: There may be a difference in respiratory mechanics, inflammatory markers, and pulmonary emboli in COVID-19 associated ARDS vs. ARDS from other etiologies. Our purpose was to determine differences in respiratory mechanics, inflammatory markers, and incidence of pulmonary embolism in patients with and without COVID-19 associated ARDS admitted in the same period and treated with a similar ventilation strategy. Methods: A cohort study of COVID-19 associated ARDS and non COVID-19 patients in a Saudi Arabian center between June 1 and 15, 2020. We measured respiratory mechanics (ventilatory ratio (VR), recruitability index (RI), markers of inflammation, and computed tomography pulmonary angiograms. Results: Forty-two patients with COVID-19 and 43 non-COVID patients with ARDS comprised the cohort. The incidence of "recruitable" patients using the recruitment/inflation ratio was slightly lower in COVID-19 patients (62 vs. 86%; p = 0.01). Fifteen COVID-19 ARDS patients (35.7%) developed a pulmonary embolism as compared to 4 (9.3%) in other ARDS patients (p = 0.003). In COVID-19 patients, a D-Dimer ≥ 5.0 mcg/ml had a 73% (95% CI 45-92%) sensitivity and 89% (95% CI 71-98%) specificity for predicting pulmonary embolism. Crude 60-day mortality was higher in COVID-19 patients (35 vs. 15%; p = 0.039) but three multivariate analysis showed that independent predictors of 60-day mortality included the ventilatory ratio (OR 3.67, 95% CI 1.61-8.35), PaO2/FIO2 ratio (OR 0.93; 95% CI 0.87-0.99), IL-6 (OR 1.02, 95% CI 1.00-1.03), and D-dimer (OR 7.26, 95% CI 1.11-47.30) but not COVID-19 infection. Conclusion: COVID-19 patients were slightly less recruitable and had a higher incidence of pulmonary embolism than those with ARDS from other etiologies. A high D-dimer was predictive of pulmonary embolism in COVID-19 patients. COVID-19 infection was not an independent predictor of 60-day mortality in the presence of ARDS.

Machine learning decision tree algorithm role for predicting mortality in critically ill adult COVID-19 patients admitted to the ICU.

BACKGROUND: Coronavirus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently a major cause of intensive care unit (ICU) admissions globally. The role of machine learning in the ICU is evolving but currently limited to diagnostic and prognostic values. A decision tree (DT) algorithm is a simple and intuitive machine learning method that provides sequential nonlinear analysis of variables. It is simple and might be a valuable tool for bedside physicians during COVID-19 to predict ICU outcomes and help in critical decision-making like end-of-life decisions and bed allocation in the event of limited ICU bed capacities. Herein, we utilized a machine learning DT algorithm to describe the association of a predefined set of variables and 28-day ICU outcome in adult COVID-19 patients admitted to the ICU. We highlight the value of utilizing a machine learning DT algorithm in the ICU at the time of a COVID-19 pandemic. METHODS: This was a prospective and multicenter cohort study involving 14 hospitals in Saudi Arabia. We included critically ill COVID-19 patients admitted to the ICU between March 1, 2020, and October 31, 2020. The predictors of 28-day ICU mortality were identified using two predictive models: conventional logistic regression and DT analyses. RESULTS: There were 1468 critically ill COVID-19 patients included in the study. The 28-day ICU mortality was 540 (36.8 %), and the 90-day mortality was 600 (40.9 %). The DT algorithm identified five variables that were integrated into the algorithm to predict 28-day ICU outcomes: need for intubation, need for vasopressors, age, gender, and PaO2/FiO2 ratio. CONCLUSION: DT is a simple tool that might be utilized in the ICU to identify critically ill COVID-19 patients who are at high risk of 28-day ICU mortality. However, further studies and external validation are still required.

Plasma exchange in the treatment of complex COVID-19-related critical illness: controversies and perspectives.

COVID-19 (coronavirus disease 2019), caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), emerged in Wuhan, China, and has spread worldwide, resulting in over 73 million cases and more than 1 600 000 deaths as of December 2020. Although the disease is asymptomatic in most cases, some patients develop life-threatening disease characterised by acute respiratory distress syndrome, sepsis, multisystem organ failure (MSOF), extrapulmonary manifestations, thromboembolic disease and associated cytokine release syndrome. The rationale for applying therapeutic plasma exchange (TPE) early in the course of fulminant COVID-19 is the suppression of thromboinflammation and amelioration of microangiopathy, thus preventing the ensuing MSOF. In the course of complicated critical illness due to COVID-19, immune dysregulation may be as important as viral replication itself. Moreover, the natural course of SARS-CoV-2 infection remains obscure, as re-infections and/or recurrently positive real-time PCR results have been reported. Although concerns still exist regarding its potential immunosuppressive effects and safety, TPE shows promise in the management of life-threatening COVID-19 as documented by various pilot studies, which remain to be confirmed by future randomised controlled trials. However, current data suggest that TPE could be an adjunctive rescue therapy in complex COVID-19 critical illness.

Renal Tubular Acidosis in Critically Ill Patients with Coronavirus Disease 2019 Acute Respiratory Distress Syndrome.

The coronavirus disease 2019 (COVID-19) infection associated with multisystemic involvement including renal manifestations has been described in the literature. The recent data show a high mortality rate of 60%-90% once renal function begins to deteriorate. We report on three patients who were admitted to intensive care unit due to severe COVID-19 acute respiratory distress syndrome and developed distal renal tubular acidosis. The three COVID-19 patients had hyperchloremic acidosis which was investigated thoroughly through a biochemical analysis of arterial blood gases and urine test as well as serological tests for autoimmune diseases and chronic infections, in addition to renal ultrasound. Metabolic acidosis was managed through repeated doses of intravenous sodium bicarbonate therapy; however, continuous renal replacement therapy was initiated for two refractory cases. We found that severe COVID-19 infection may be accompanied by hyperchloremic acidosis due to the cytopathic damage of the distal renal tubules, making the buffering system nonefficient and if not managed adequately, it may lead to poor prognosis.

A Retrospective Analysis of Thromboembolic Phenomena in Mechanically Ventilated Patients with COVID-19.

BACKGROUND: Recent studies have shown an increased prevalence of thromboembolic disease in critically ill patients with the novel SARS-CoV-2 disease (COVID-19). However, the use of enhanced anticoagulation therapy in these patients remains controversial. OBJECTIVES: To determine the incidence of thromboembolic phenomena (TEP) and hemorrhagic events (HEs) in intensive care unit (ICU) COVID-19 patients. METHODS: One hundred and sixty ICU patients with COVID-19 were enrolled. Clinical examination results, laboratory data, and imaging studies (computed tomography/Doppler ultrasound scans) for these patients were retrospectively collected and analyzed. Outcome measures including days on mechanical ventilation, ICU length of stay, and day-28 mortality were recorded. RESULTS: Sixty patients (37.5%) developed TEP including thirty patients with deep vein thrombosis, 55 patients with pulmonary embolism, and 7 patients with arterial thromboembolism. Cardiac arrhythmias, lymphocytopenia, and increased D-dimers were more frequently observed in the TEP group compared to the non-TEP group of patients (all p < 0.05). The sensitivity, specificity, and positive and negative predictive values of a cutoff D-dimer level of 3.0 µg/mL for predicting PE were 74.5%, 95.1%, 86.8%, and 91.9%, respectively. Thirteen patients experienced HEs, which were more frequently observed in the TEP group (p < 0.05). Twenty-eight-day mortality was higher in the TEP group (60%) compared to the non-TEP group (30%) of patients (p=0.02). CONCLUSIONS: The rates of TEP and HEs in mechanically ventilated critically ill COVID-19 patients were 37. 5% and 8.1%. Twenty-eight-day mortality was higher in the TEP group (60%) compared to the non-TEP group (30%) of patients.

Therapeutic plasma exchange in patients with life-threatening COVID-19: a randomised controlled clinical trial.

Assessment of efficacy of therapeutic plasma exchange (TPE) following life-threatening COVID-19. This was an open-label, randomised clinical trial of ICU patients with life-threatening COVID-19 (positive RT-qPCR plus ARDS, sepsis, organ failure, hyperinflammation). Study was terminated after 87/120 patients enrolled. Standard treatment plus TPE (n = 43) versus standard treatment (n = 44), and stratified by PaO2/FiO2 ratio (>150 vs. ≤150), were compared. Primary outcomes were 35-day mortality and TPE safety. Secondary outcomes were association between TPE and mortality, improvement in SOFA score, change in inflammatory biomarkers, days on mechanical ventilation (MV), and ICU length of stay (LOS). Eighty-seven patients [median age 49 (IQR 34-63) years; 82.8% male] were randomised (44 standard care; 43 standard care plus TPE). Days on MV (P = 0.007) and ICU LOS (P = 0.02) were lower in the TPE group. 35-Day mortality was non-significantly lower in the TPE group (20.9% vs. 34.1%; Kaplan-Meier, P = 0.582). TPE was associated with increased lymphocytes and ADAMTS-13 activity and decreased serum lactate, lactate dehydrogenase, ferritin, d-dimers and interleukin-6. Multivariable regression analysis provided several predictors of 35-day mortality: PaO2/FiO2 ratio (HR, 0.98, 95% CI 0.96-1.00; P = 0.02]; ADAMTS-13 activity (HR, 0.89, 95% CI 0.82-0.98; P = 0.01); pulmonary embolism (HR, 3.57, 95% CI 1.43-8.92; P = 0.007). Post-hoc analysis revealed a significant reduction in SOFA score for TPE patients (P < 0.05). In critically-ill COVID-19 patients, addition of TPE to standard ICU therapy was associated with faster clinical recovery and no increased 35-day mortality.

Efficacy of tocilizumab in patients with severe COVID-19: Survival and clinical outcomes.

BACKGROUND: SARS-CoV-2 is associated with a severe inflammatory response contributing to respiratory and systemic manifestations, morbidity, and mortality in patients with coronavirus disease 2019 (COVID-19). METHODS: Tocilizumab (TCZ) efficacy on mortality and length of hospital stay was retrospectively evaluated in patients who received TCZ and compared with that in controls with a similar severity of COVID-19. The primary endpoint was survival probability on day 28. The secondary endpoints included survival at day 14 and length of hospital stay. RESULTS: Of the 148 patients included in the study, 62 received TCZ and standard of care, whereas 86 served as a control group and received only standard of care. The two groups were similar, although TCZ-treated patients were more likely to exhibit hypertension (46.7% vs. 29.8%), chronic kidney disease (14.5% vs. 1.1%), and high Charlson score (1.18 vs. 1.00; p = 0.006) and less likely to receive corticosteroid treatment (48.5% vs. 93.0%). TCZ was associated with lower mortality on both day 28 (16.1% vs. 37.2%, p = 0.004) and day 14 (9.7% vs. 24.4%, p = 0.022). The hospital stay was longer in the TCZ-treated than in the control group (15.6 ± 7.59 vs.17.7 ± 7.8 days, p = 0.103). Ten patients (16.0%) in the TCZ-treated group developed infections. CONCLUSION: TCZ was associated with a lower likelihood of death despite resulting in higher infection rates and a non-significant longer hospital stay.

Clinical Characteristics and Predictors of 28-Day Mortality in 352 Critically Ill Patients with COVID-19: A Retrospective Study.

BACKGROUND: Since the first COVID-19 patient in Saudi Arabia (March, 2020) more than 338,539 cases and approximately 4996 dead were reported. We present the main characteristics and outcomes of critically ill COVID-19 patients that were admitted in the largest Ministry of Health Intensive Care Unit (ICU) in Saudi Arabia. METHODS: This retrospective study, analyzed routine epidemiologic, clinical, and laboratory data of COVID-19 critically ill patients in King Saud Medical City (KSMC), Riyadh, Saudi Arabia, between March 20, 2020 and May 31, 2020. Severe acute respiratory syndrome coronavirus-2 infection was confirmed by real-time reverse transcriptase polymerase chain reaction assays performed on nasopharyngeal swabs in all enrolled cases. Outcome measures such as 28-days mortality, duration of mechanical ventilation, and ICU length of stay were analyzed. RESULTS: Three-hundred-and-fifty-two critically ill COVID-19 patients were included in the study. Patients had a mean age of 50.63 ± 13.3 years, 87.2% were males, and 49.4% were active smokers. Upon ICU admission, 56.8% of patients were mechanically ventilated with peripheral oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) ratio of 158 ± 32. No co-infections with other endemic viruses were observed. Duration of mechanical ventilation was 16 (IQR: 8-28) days; ICU length of stay was 18 (IQR: 9-29) days, and 28-day mortality was 32.1%. Multivariate regression analysis showed that old age [Odds Ratio (OR): 1.15, 95% Confidence Intervals (CI): 1.03-1.21], active smoking [OR: 3, 95% CI: 2.51-3.66], pulmonary embolism [OR: 2.91, 95% CI: 2.65-3.36), decreased SpO2/FiO2 ratio [OR: 0.94, 95% CI: 0.91-0.97], and increased lactate [OR: 3.9, 95% CI: 2.4-4.9], and D-dimers [OR: 2.54, 95% CI: 1.57-3.12] were mortality predictors. CONCLUSION: Old age, active smoking, pulmonary embolism, decreased SpO2/FiO2 ratio, and increased lactate and D-dimers were predictors of 28-day mortality in critically ill COVID-19 patients.