Factors Associated With Prolonged Ventilation in Patients Receiving Prone Positioning Protocol With Muscle Relaxants for Severe COVID-19 Pneumonia.

BACKGROUND: Prone positioning and neuromuscular blocking agents (NMBAs) are frequently used to treat severe respiratory failure from COVID-19 pneumonia. Prone positioning has shown to improve mortality, whereas NMBAs are used to prevent ventilator asynchrony and reduce patient self-inflicted lung injury. However, despite the use of lung-protective strategies, high death rates in this patient population have been reported. METHODS: We retrospectively examined the factors affecting prolonged mechanical ventilation in patients receiving prone positioning plus muscle relaxants. The medical records of 170 patients were reviewed. Subjects were divided into 2 groups according to ventilator-free days (VFDs) at day 28. Whereas subjects with VFDs < 18 d were defined as prolonged mechanical ventilation, subjects with VFDs ≥18 d were defined as short-term mechanical ventilation. Subjects' baseline status, status at ICU admission, therapy before ICU admission, and treatment in the ICU were studied. RESULTS: Under the proning protocol for COVID-19, the mortality rate in our facility was 11.2%. The prognosis may be improved by avoiding lung injury in the early stages of mechanical ventilation. According to multifactorial logistic regression analysis, persistent SARS-CoV-2 viral shedding in blood (P = .027), higher daily corticosteroid use before ICU admission (P = .007), delayed recovery of lymphocyte count (P < .001), and higher maximal fibrinogen degradation products (P = .039) were associated with prolonged mechanical ventilation. A significant relationship was found between daily corticosteroid use before admission and VFDs by squared regression analysis (y = -0.00008522x2 + 0.01338x + 12.8; x: daily corticosteroids dosage before admission [prednisolone mg/d]; y: VFDs/28 d, R2 = 0.047, P = .02). The peak point of the regression curve was 13.4 d at 78.5 mg/d of the equivalent prednisolone dose, which corresponded to the longest VFDs. CONCLUSIONS: Persistent SARS-CoV-2 viral shedding in blood, high corticosteroid dose from the onset of symptoms to ICU admission, slow recovery of lymphocyte counts, and high levels of fibrinogen degradation products after admission were associated with prolonged mechanical ventilation in subjects with severe COVID-19 pneumonia.

Personalized ventilatory strategy based on lung recruitablity in COVID-19-associated acute respiratory distress syndrome: a prospective clinical study.

BACKGROUND: Heterogeneity is an inherent nature of ARDS. Recruitment-to-inflation ratio has been developed to identify the patients who has lung recruitablity. This technique might be useful to identify the patients that match specific interventions, such as higher positive end-expiratory pressure (PEEP) or prone position or both. We aimed to evaluate the physiological effects of PEEP and body position on lung mechanics and regional lung inflation in COVID-19-associated ARDS and to propose the optimal ventilatory strategy based on recruitment-to-inflation ratio. METHODS: Patients with COVID-19-associated ARDS were consecutively enrolled. Lung recruitablity (recruitment-to-inflation ratio) and regional lung inflation (electrical impedance tomography [EIT]) were measured with a combination of body position (supine or prone) and PEEP (low 5 cmH2O or high 15 cmH2O). The utility of recruitment-to-inflation ratio to predict responses to PEEP were examined with EIT. RESULTS: Forty-three patients were included. Recruitment-to-inflation ratio was 0.68 (IQR 0.52-0.84), separating high recruiter versus low recruiter. Oxygenation was the same between two groups. In high recruiter, a combination of high PEEP with prone position achieved the highest oxygenation and less dependent silent spaces in EIT (vs. low PEEP in both positions) without increasing non-dependent silent spaces in EIT. In low recruiter, low PEEP in prone position resulted in better oxygenation (vs. both PEEPs in supine position), less dependent silent spaces (vs. low PEEP in supine position) and less non-dependent silent spaces (vs. high PEEP in both positions). Recruitment-to-inflation ratio was positively correlated with the improvement in oxygenation and respiratory system compliance, the decrease in dependent silent spaces, and was inversely correlated with the increase in non-dependent silent spaces, when applying high PEEP. CONCLUSIONS: Recruitment-to-inflation ratio may be useful to personalize PEEP in COVID-19-associated ARDS. Higher PEEP in prone position and lower PEEP in prone position decreased the amount of dependent silent spaces (suggesting lung collapse) without increasing the amount of non-dependent silent spaces (suggesting overinflation) in high recruiter and in low recruiter, respectively.

Association between tracheostomy and survival in patients with coronavirus disease 2019 who require prolonged mechanical ventilation for more than 14 days: A multicenter cohort study.

OBJECTIVE: Tracheostomy is a common procedure with potential prognostic advantages for patients who require prolonged mechanical ventilation (PMV). Early recommendations for patients with coronavirus disease 2019 (COVID-19) suggested delayed or limited tracheostomy considering the risk for viral transmission to clinicians. However, updated guidelines for tracheostomy with appropriate personal protective equipment have revised its indications. This study aimed to evaluate the association between tracheostomy and prognosis in patients with COVID-19 requiring PMV. METHODS: This was a multicenter, retrospective cohort study using data from the nationwide Japanese Intensive Care PAtient Database. We included adult patients aged ≥16 years who were admitted to the intensive care unit (ICU) due to COVID-19 and who required PMV (for >14 days or until performance of tracheostomy). The primary outcome was hospital mortality, and the association between implementation of tracheostomy and patient prognosis was assessed using weighted Cox proportional hazards regression analysis with inverse probability of treatment weighting (IPTW) using the propensity score to address confounders. RESULTS: Between January 2020 and February 2021, 453 patients with COVID-19 were observed. Data from 109 patients who required PMV were analyzed: 66 (60.6%) underwent tracheostomy and 38 (34.9%) died. After adjusting for potential confounders using IPTW, tracheostomy implementation was found to significantly reduce hospital mortality (hazard ratio [HR]: 0.316, 95% confidence interval [CI]: 0.163-0.612). Patients who underwent tracheostomy had a similarly decreased ICU and 28-day mortality (HR: 0.269, 95% CI: 0.124-0.581; HR 0.281, 95% CI: 0.094-0.839, respectively). A sensitivity analysis using different definitions of PMV duration consistently showed reduced mortality in patients who underwent tracheostomy. CONCLUSION: The implementation of tracheostomy was associated with favorable patient prognosis among patients with COVID-19 requiring PMV. Our findings support proactive tracheostomy in critically ill patients with COVID-19 requiring mechanical ventilation for >14 days.

Establishment and clinical application of SARS-CoV-2 catch column.

BACKGROUND: A certain number of patients with coronavirus disease 2019 (COVID-19), particularly those who test positive for SARS-CoV-2 in the serum, are hospitalized. Further, some even die. We examined the effect of blood adsorption therapy using columns that can eliminate SARS-CoV-2 on the improvement of the prognosis of severe COVID-19 patients. METHODS: This study enrolled seven patients receiving mechanical ventilation. The patients received viral adsorption therapy using SARS-catch column for 3 days. The SARS-catch column was developed by immobilizing a specific peptide, designed based on the sequence of human angiotensin-converting enzyme 2 (hACE2), to an endotoxin adsorption column (PMX). In total, eight types of SARS-CoV-2-catch (SCC) candidate peptides were developed. Then, a clinical study on the effects of blood adsorption therapy using the SARS-catch column in patients with severe COVID-19 was performed, and the data in the present study were compared with historical data of severe COVID-19 patients. RESULTS: Among all SCC candidate peptides, SCC-4N had the best adsorption activity against SARS-CoV-2. The SARS-catch column using SCC-4N removed 65% more SARS-CoV-2 than PMX. Compared with historical data, the weaning time from mechanical ventilation was faster in the present study. In addition, the rate of negative blood viral load in the present study was higher than that in the historical data. CONCLUSION: The timely treatment with virus adsorption therapy may eliminate serum SARS-CoV-2 and improve the prognosis of patients with severe COVID-19. However, large-scale studies must be performed in the future to further assess the finding of this study (jRCTs052200134).

Secondary subcutaneous abscess due to mixed infections by Peptoniphilus olsenii and Gleimia europaea after COVID-19.

This report described a rare case of subcutaneous anaerobic bacterial abscess due to Peptoniphilus olsenii and Gleimia europaea after COVID-19. The patient received incision and drainage of the abscess and antibiotics, thereby achieving recovery. Immunodeficiency related to COVID-19 and its treatment might contribute to secondary skin and subcutaneous bacterial infections.

Timing of tracheostomy and patient outcomes in critically ill patients requiring extracorporeal membrane oxygenation: a single-center retrospective observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an integral method of life support in critically ill patients with severe cardiopulmonary failure; however, such patients generally require prolonged mechanical ventilation and exhibit high mortality rates. Tracheostomy is commonly performed in patients on mechanical ventilation, and its early implementation has potential advantages for favorable patient outcomes. This study aimed to investigate the association between tracheostomy timing and patient outcomes, including mortality, in patients requiring ECMO. METHODS: We conducted a single-center retrospective observational study of consecutively admitted patients who were supported by ECMO and underwent tracheostomy during intensive care unit (ICU) admission at a tertiary care center from April 2014 until December 2021. The primary outcome was hospital mortality. Using the quartiles of tracheostomy timing, the patients were classified into four groups for comparison. The association between the quartiles of tracheostomy timing and mortality was explored using multivariable logistic regression models. RESULTS: Of the 293 patients treated with ECMO, 98 eligible patients were divided into quartiles 1 (≤ 15 days), quartile 2:16-19 days, quartile 3:20-26 days, and 4 (> 26 days). All patients underwent surgical tracheostomy and 35 patients underwent tracheostomy during ECMO. The complications of tracheostomy were comparable between the groups, whereas the duration of ECMO and ICU length of stay increased significantly as the quartiles of tracheostomy timing increased. Patients in quartile 1 had the lowest hospital mortality rate (19.2%), whereas those in quartile 4 had the highest mortality rate (50.0%). Multivariate logistic regression analysis showed a significant association between the increment of the quartiles of tracheostomy timing and hospital mortality (adjusted odds ratio for quartile increment:1.55, 95% confidence interval 1.03-2.35, p for trend = 0.037). CONCLUSIONS: The timing of tracheostomy in patients requiring ECMO was significantly associated with patient outcomes in a time-dependent manner. Further investigation is warranted to determine the optimal timing of tracheostomy in terms of mortality.

Control of blood glucose levels by an artificial pancreas in patients with severe coronavirus disease 2019 pneumonia.

BACKGROUND: Many patients with severe coronavirus disease 2019 (COVID-19) pneumonia experience hyperglycemia. It is often difficult to control blood glucose (BG) levels in such patients using standard intravenous insulin infusion therapy. Therefore, we used an artificial pancreas. This study aimed to compare the BG status of the artificial pancreas with that of standard therapy. METHODS: Fifteen patients were included in the study. BG values and the infusion speed of insulin and glucose by the artificial pancreas were collected. Arterial BG and administration rates of insulin, parenteral sugar, and enteral sugar were recorded during the artificial pancreas and standard therapy. The target BG level was 200 mg/dl. RESULTS: Arterial BG was highly correlated with BG data from the artificial pancreas. A higher BG slightly increased the difference between the BG data from the artificial pancreas and arterial BS. No significant difference in arterial BG was observed between the artificial pancreas and standard therapy. However, the standard deviation with the artificial pancreas was smaller than that under standard therapy (p < 0.0001). More points within the target BG range were achieved with the artificial pancreas (180-220 mg/dl) than under standard therapy. The hyperglycemic index of the artificial pancreas (8.7 ± 15.6 mg/dl) was lower than that of standard therapy (16.0 ± 21.5 mg/dl) (p = 0.0387). No incidence of hypoglycemia occurred under the artificial pancreas. CONCLUSIONS: The rate of achieving target BG was higher using artificial pancreas than with standard therapy. An artificial pancreas helps to control BG in critically ill patients.

Ischemic Stroke Due to Heparin-induced Thrombocytopenia during Severe COVID-19 Infection.

A 53-year-old woman with severe coronavirus disease 2019 (COVID-19) pneumonia was admitted and treated with intravenous unfractionated heparin for thromboprophylaxis under general anesthesia with mechanical ventilation. She developed right hemiparesis after hospitalization due to a large hemorrhagic infarction. Her platelet count decreased from 243,000/µL at administration to 121,000/µL. Anti-platelet factor 4-heparin antibody testing was positive according to a latex immunoturbidimetric assay. She was therefore diagnosed with heparin-induced thrombocytopenia. We immediately stopped the heparin and started argatroban; the platelet count recovered, and thrombosis did not relapse. Physicians should consider heparin-induced thrombocytopenia as a cause of ischemic stroke in patients with COVID-19 infection.

COVID-19 in a human T-cell lymphotropic virus type-1 carrier.

This is the first report of COVID-19 in a human T-cell lymphotropic virus type-1 (HTLV-1) carrier. HTLV-1 infection can cause immune dysfunction even in asymptomatic carriers. This case highlights the need for guidance on management of COVID-19-HTLV-1 coinfection, specifically on the appropriate use of corticosteroid treatment while considering secondary infection.

Ivermectin administration is associated with lower gastrointestinal complications and greater ventilator-free days in ventilated patients with COVID-19: A propensity score analysis.

INTRODUCTION: COVID-19 patients have been reported to have digestive symptoms with poor outcome. Ivermectin, an antiparasitic drug, has been used in COVID-19 patients. The objective of this study was to evaluate whether ivermectin has effects on gastrointestinal complications and ventilator-free days in ventilated patients with COVID-19. METHODS: COVID-19 patients who were mechanically ventilated in the ICU were included in this study. The ventilated patients who received ivermectin within 3 days after admission were assigned to the Ivermectin group, and the others were assigned to the Control group. Patients in the Ivermectin group received ivermectin 200 µg/kg via nasal tube. The incidence of gastrointestinal complications and ventilator-free days within 4 weeks from admission were evaluated as clinical outcomes using a propensity score with the inverse probability weighting method. RESULTS: We included 88 patients in this study, of whom 39 patients were classified into the Ivermectin group, and 49 patients were classified into the Control group. The hazard ratio for gastrointestinal complications in the Ivermectin group as compared with the Control group was 0.221 (95% confidence interval [CI], 0.057 to 0.855; p = 0.029) in a Cox proportional-hazard regression model. The odds ratio for ventilator-free days as compared with the Control group was 1.920 (95% CI, 1.076 to 3.425; p = 0.027) in a proportional odds logistic regression model. CONCLUSIONS: Ivermectin improved gastrointestinal complications and the number of ventilator-free days in severe COVID-19 patients undergoing mechanical ventilation. Prevention of gastrointestinal symptoms by SARS-Cov-2 might be associated with COVID-19 outcome.

Prolonged corticosteroid therapy and cytomegalovirus infection in patients with severe COVID-19.

Systemic corticosteroid therapy is frequently used to treat coronavirus disease 2019 (COVID-19). However, its maximum duration without secondary infections remains unclear. We aimed to evaluate the utility of monitoring cytomegalovirus (CMV) infection in patients with COVID-19 and estimate the maximum duration of systemic corticosteroid therapy without secondary infections. We included 59 patients with severe COVID-19 without CMV infection on admission to the intensive care unit (ICU). All patients received systemic corticosteroid therapy under invasive mechanical ventilation, with examination for plasma CMV-deoxyribonucleic acid (DNA) levels during the ICU stay. We analyzed the correlations among patient characteristics, CMV infection, diseases, and patient mortality. CMV infections were newly identified in 15 (25.4%) patients; moreover, anti-CMV treatment was administered to six (10.2%) patients during the ICU stay. Four (6.8%) patients had secondary infection-related mortality. The cumulative incidences of CMV infection and anti-CMV treatment during the ICU stay were 26.8% (95% confidence interval [CI], 15.8%-39.0%) and 12.3% (95% CI, 4.8%-23.4%), respectively. Furthermore, the median duration of systemic corticosteroid therapy without CMV infection was 15 days (95% CI, 13-16 days). The presence of CMV infection was associated with mortality during the ICU stay (p = 0.003). Monitoring plasma CMV-DNA levels could facilitate the detection of secondary CMV infection due to prolonged systemic corticosteroid therapy. The duration of systemic corticosteroid therapy for COVID-19 should be limited.

Fatal cytomegalovirus pneumonia in a critically ill patient with COVID-19.

Coronavirus disease 2019 (COVID-19) can cause severe lymphopenia and respiratory failure requiring prolonged invasive mechanical ventilation (MV). COVID-19 patients with severe lymphopenia or respiratory failure are at risk of developing secondary infections. Here, we present the needle autopsy findings of a critically ill patient with COVID-19 who required reintubation and prolonged MV, and eventually died of secondary cytomegalovirus (CMV) pneumonia. This case highlights the potential risk of long-term steroid use and the need for routine monitoring for CMV infection in critically ill patients with COVID-19.

Individualized ventilatory management in patients with COVID-19-associated acute respiratory distress syndrome.

Due to the coronavirus disease 2019 pandemic, the number of coronavirus disease 2019-associated acute respiratory distress syndrome is rapidly increasing. The heterogeneity of coronavirus disease 2019-associated acute respiratory distress syndrome contributes to the complexity of managing patients. Here we described two patients with coronavirus disease 2019-associated acute respiratory distress syndrome showing that the bedside physiological approach including careful evaluation of respiratory system mechanics and visualization of ventilation with electrical impedance tomography was useful to individualize ventilatory management.