Improved survival in COVID-19 related sepsis and ARDS treated with a unique "triple therapy" including therapeutic plasma exchange: A single center retrospective analysis.

BACKGROUND: Throughout the COVID-19 pandemic, the mortality of critically ill patients remained high. Our group developed a treatment regimen targeting sepsis and ARDS which we labeled "triple therapy" consisting of (1) corticosteroids, (2) therapeutic plasma exchange (TPE), and (3) timely intubation with lung protective ventilation. Our propensity analysis assesses the impact of triple therapy on survival in COVID-19 patients with sepsis and ARDS. METHODS: Retrospective propensity analysis comparing triple therapy to no triple therapy in adult critically ill COVID-19 patients admitted to the Intensive Care Unit at Lexington Medical Center from 1 March 2020 through 31 October 2021. RESULTS: Eight hundred and fifty-one patients were admitted with COVID-19 and 53 clinical and laboratory variables were analyzed. Multivariable analysis revealed that triple therapy was associated with increased survival (OR: 1.91; P = .008). Two propensity score-adjusted models demonstrated an increased likelihood of survival in patients receiving triple therapy. Patients with thrombocytopenia were among those most likely to experience increased survival if they received early triple therapy. Decreased survival was observed with endotracheal intubation ≥7 days from hospital admission (P < .001) and there was a trend toward decreased survival if TPE was initiated ≥6 days from hospital admission (P = .091). CONCLUSION: Our analysis shows that early triple therapy, defined as high-dose methylprednisolone, TPE, and timely invasive mechanical ventilation within the first 96 hours of admission, may improve survival in critically ill septic patients with ARDS secondary to COVID-19 infection. Further studies are needed to define specific phenotypes and characteristics that will identify those patients most likely to benefit.

High-Frequency Oscillatory Ventilation for Refractory Hypoxemia in Severe COVID-19 Pneumonia: A Small Case Series.

BACKGROUND COVID-19 continues to place a tremendous burden on the healthcare system, with most deaths resulting from respiratory failure. Management strategies have varied, but the mortality rate for mechanically ventilated patients remains high. Conventional management with ARDSnet ventilation can improve outcomes but alternative and adjunct treatments continue to be explored. High-frequency oscillatory ventilation (HFOV), a modality now rarely used in adult critical care medicine, may offer an alternative treatment option by maximizing lung protection and limiting oxygen toxicity in critically ill patients failing conventional ventilator strategies. CASE REPORT We present 3 patients with severe acute respiratory distress syndrome (ARDS) and sepsis due to COVID-19 who all improved clinically after transitioning from conventional ventilation to HFOV. Two patients developed refractory hypoxemia with hemodynamic instability and multiple organ failure requiring vasopressor support and renal replacement therapy. After failing to improve with all available therapies, both patients stabilized and ultimately improved after being placed on HFOV. The third patient developed severe volutrauma/barotrauma despite extreme lung protection and ARDSnet ventilation. He showed improvement in oxygenation and signs of lung trauma slowly improved after initiating HFOV. All 3 patients were ultimately liberated from mechanical ventilation and discharged from the hospital to return to functional independence. CONCLUSIONS Our experience suggests that HFOV offers advantages in the management of certain critically ill patients with ARDS due to COVID-19 pneumonia and might be considered in cases refractory to standard management strategies.

The successful use of therapeutic plasma exchange for severe COVID-19 acute respiratory distress syndrome with multiple organ failure.

The COVID-19 pandemic has brought about an urgent need for effective treatment, while conserving vital resources such as intensive care unit beds and ventilators. Antivirals, convalescent plasma, and biologics have been used with mixed results. The profound "cytokine storm" induced endotheliopathy and microthrombotic disease in patients with COVID-19 may lead to acute respiratory distress syndrome, sepsis, and multi-organ failure. We present a case of SARS-COV2 pneumonia with septic shock and multi-organ failure that demonstrated significant clinical improvement after therapeutic plasma exchange. A 65-year-old female with multiple comorbidities presented with progressive dyspnea and dry cough. She was found to be COVID-19 positive with pneumonia, and developed progressive hypoxemia and shock requiring vasopressors, cardioversion, and non-invasive positive pressure ventilation. Given her worsening sepsis with multi-organ failure, she underwent therapeutic plasma exchange with rapid clinical improvement. Her case supports the theory that plasma exchange may help abate the "cytokine storm" induced endotheliopathy and microthrombosis associated with COVID-19. Further studies are needed to identify markers of this pathway and the potential role of plasma exchange in these critically ill patients.

Dysregulation in microRNA expression in peripheral blood mononuclear cells of sepsis patients is associated with immunopathology.

Sepsis is a major cause of death worldwide. It triggers systemic inflammation, the role of which remains unclear. In the current study, we investigated the induction of microRNA (miRNA) during sepsis and their role in the regulation of inflammation. Patients, on days 1 and 5 following sepsis diagnosis, had reduced T cells but elevated monocytes. Plasma levels of IL-6, IL-8, IL-10 and MCP-1 dramatically increased in sepsis patients on day 1. T cells from sepsis patients differentiated primarily into Th2 cells, whereas regulatory T cells decreased. Analysis of 1163 miRNAs from PBMCs revealed that miR-182, miR-143, miR-145, miR-146a, miR-150, and miR-155 were dysregulated in sepsis patients. miR-146a downregulation correlated with increased IL-6 expression and monocyte proliferation. Bioinformatics analysis uncovered the immunological associations of dysregulated miRNAs with clinical disease. The current study demonstrates that miRNA dysregulation correlates with clinical manifestations and inflammation, and therefore remains a potential therapeutic target against sepsis.

Dural venous thrombosis following splenectomy in a patient with hereditary spherocytosis.

Hereditary spherocytosis is a common form of hemolytic anemia sometimes requiring splenectomy in recalcitrant cases. The complications of splenectomy include an increased risk of thrombosis, usually presenting with deep vein thrombosis or pulmonary embolism. However, common complaints such as headache should warn clinicians of involvement in less common sites, primarily the dural venous system. The case of dural venous thrombosis in a patient with hereditary spherocytosis and splenectomy is discussed. The potential mechanisms associated with thrombosis formation in this population and its treatment are discussed.

Hypoxemia secondary to right-to-left interatrial shunt through a patent foramen ovale in a patient with an elevated right hemidiaphragm.

Though uncommon, right-to-left shunt through a patent foramen ovale with normal right-side pressure and with a normal interatrial pressure gradient has been reported. The speculated pathophysiology is attributed to directional blood flow streaming from the vena cava to the left atrium. Hypoxemia secondary to right-to-left shunt with normal pulmonary artery pressure has been extensively documented after right pneumonectomy. Five prior cases have documented hypoxemia secondary to a right-to-left shunt through a patent foramen ovale in the presence of an elevated right hemidiaphragm. This is the sixth documented case of right-to-left shunt through a patent foramen ovale in the presence of an elevated right hemidiaphragm with a similar presentation in which closure of the patent foramen ovale resulted in resolution of hypoxemia.

Post-endoscopy checklist reduces length of stay for non-variceal upper gastrointestinal bleeding.

OBJECTIVE: To examine the effect of improved gastroenterologist-to-admitting service communication on hospital stay for upper gastrointestinal bleeding. HYPOTHESIS: a detailed checklist addressing factors relevant to discharge planning would shorten hospital stay, when added to the procedure report. DESIGN: Pre-post intervention design, recording balance measures (potential confounders). SETTING: A Canadian university hospital. STUDY PARTICIPANTS: Intermittent 5- to 7-day batches of consecutive emergency patients presenting with non-variceal upper gastrointestinal bleeding as their primary problem. The durations of the background and intervention periods were 3 months (beginning 9 June 2003) and 4 weeks (beginning 8 September 2003), respectively. INTERVENTION: The gastrointestinal bleeding Quality Improvement and Health Information multidisciplinary team (quality improvement personnel; emergency physicians, hospitalists, gastroenterologists, in-patient and endoscopy nurses) developed a one-page checklist, outlining detailed recommendations (3-Ds-diet, drugs, discharge plan) to append to the procedure report. MAIN OUTCOME MEASURES: Difference in median length of hospital stay was the primary endpoint. As balance measures, demographics, bleeding severity, comorbidities, readmission rates, and various benchmark times were recorded prospectively. RESULTS: Thirty-nine patients met the criteria in the background period (4 months, intermittently sampled), and 22 in the intervention period (4 weeks, continuously sampled). There were no significant baseline differences. Median in-patient stay was 7.0 (95% interquartile range 2-24) versus 3.5 (95% interquartile range 1-12) days for the background and intervention periods, respectively (P = 0.003). This remained significant when outliers (stay > 10 days) were removed (P = 0.02). CONCLUSION: A checklist, with very specific recommendations to the admitting service, significantly reduced hospital stay for non-variceal gastrointestinal bleeding.

Utility of preoperative scores for predicting morbidity after cholecystectomy in patients with cirrhosis.

BACKGROUND & AIMS: Patients with cirrhosis have an increased risk for cholelithiasis but also have an increased risk for morbidity and mortality after cholecystectomy. Current preoperative assessment of surgical risk is imprecise. Our aims were to identify preoperative factors that would accurately predict the risk for cholecystectomy in patients with cirrhosis. METHODS: Preoperative clinical or biochemical parameters were determined for 33 patients with cirrhosis and 31 age- and sex-matched patients without cirrhosis. The use of these parameters and of the Child-Pugh and model for end-stage liver disease (MELD) scores as preoperative predictors of outcome after surgery were assessed. RESULTS: There were 2 deaths, both in cirrhotic patients. The overall risk for morbidity or mortality was increased in cirrhotic patients compared with controls. Postoperative morbidity was significantly associated with preoperative increases of international normalized ratio >1.2, bilirubin >1.0 mg/dL, creatinine >1.4 mg/dL, and a decreased platelet count <150 x 10(3) /mL. The MELD and Child-Pugh scores accurately predicted postoperative morbidity, with an area under the curve of 0.938 and 0.839, respectively. A preoperative MELD score of > or =8 had a sensitivity of 91% and a specificity of 77% for predicting postoperative morbidity. Persons with a MELD score of > or =8 had increased 30- and 90-day global charges and increased blood product usage. CONCLUSIONS: Preoperative biochemical parameters, international normalized ratio, bilirubin, platelets, and creatinine can predict increased morbidity in cirrhotic patients. A MELD score of > or =8 identifies a group at high risk for postoperative morbidity after cholecystectomy.