Predictive Accuracy of the Breathing Frequency-Ratio of Oxygen Saturation Index for Re-Intubation in Mechanically Ventilated Subjects With COVID-19.

BACKGROUND: Several studies have suggested that high-flow nasal cannula (HFNC) is useful for respiratory support after extubation in subjects with COVID-19 pneumonia, whereas 18.2% subsequently needed to undergo re-intubation. This study aimed to evaluate whether the breathing frequency (f)-ratio of oxygen saturation (ROX) index, which has been shown to be useful for predicting future intubation, is also useful for re-intubation in subjects with COVID-19. METHODS: We retrospectively analyzed mechanically ventilated subjects with COVID-19 who underwent HFNC therapy after extubation at 4 participating hospitals between January 2020-May 2022. We evaluated the predictive accuracy of ROX at 0, 1, and 2 h for re-intubation until ICU discharge and compared the area under the receiver operating characteristic (ROC) curve of the ROX index with those of f and SpO2 /FIO2 . RESULTS: Among the 248 subjects with COVID-19 pneumonia, 44 who underwent HFNC therapy after extubation were included. A total of 32 subjects without re-intubation were classified into the HFNC success group, and 12 with re-intubation were classified into the failure group. The overall trend that the area under the ROC curve of the ROX index was greater than that of the f and SaO2 /FIO2 was observed, although there was no statistical significance at any time point. The ROX index at 0 h, at the cutoff point of < 7.44, showed a sensitivity and specificity of 0.42 and 0.97, respectively. A trend of positive correlation between the time until re-intubation and ROX index at each time point was observed. CONCLUSIONS: The ROX index in the early phase of HFNC therapy after extubation was useful for predicting re-intubation with high accuracy in mechanically ventilated subjects with COVID-19. We may need close observation for subjects with < 7.44 ROX index just after extubation because of their high risk for re-intubation.

Lung Abscess and Pyothorax in Critically Ill COVID-19 Patients: A Single-Center Retrospective Study.

The mortality rate of patients with COVID-19 pneumonia requiring mechanical ventilation remains high. This study determined the percentage and characteristics of patients who developed lung abscesses or pyothorax and their mortality rates among adult patients with COVID-19 admitted to the ICU who required mechanical ventilation. Of the 64 patients with COVID-19 assessed, 30 (47%) developed ventilator-associated pneumonia (VAP), of whom 6 (20%) developed pyothorax or lung abscess. There were no statistically significant differences in patient characteristics, treatment after ICU admission, or outcomes between those with and without these complications, except for age. VAP complicated by Lung abscess or pyothorax was caused by a single organism, with Staphylococcus aureus (n = 4) and Klebsiella species (n = 2) being the primary causative agents. Occur infrequently in patients with COVID-19 requiring mechanical ventilation. Large-scale studies are required to elucidate their effects on clinical outcomes.

Temperature management using an intervascular cooling device for a COVID-19 patient with refractory hyperthermia.

COVID-19 is a life-threatening disease complicated by hyperinflammation followed by multi-organ failure. Although refractory hyperthermia in COVID-19 contributes to an unfavorable prognosis, little is known about effective interventions. We present a case of successful temperature management using an intravascular cooling device in a patient with COVID-19 who developed refractory hyperthermia.

Trends in survival during the pandemic in patients with critical COVID-19 receiving mechanical ventilation with or without ECMO: analysis of the Japanese national registry data.

BACKGROUND: The survival rate of patients with critical coronavirus disease-19 (COVID-19) over time is inconsistent in different settings. In Japan, a national database was organized to monitor and share the patient generation across the country in an immediate response to the COVID-19 pandemic. This study aimed to evaluate changes in survival over time and the prognostic factors in critical COVID-19 patients receiving mechanical ventilation with/without extracorporeal membrane oxygenation (ECMO) using the largest database in Japan. METHODS: This is a prospective observational cohort study of patients admitted to intensive care units in Japan with fatal COVID-19 pneumonia receiving mechanical ventilation and/or ECMO. We developed a prospective nationwide registry covering > 80% of intensive care units in Japan, and analyzed the association between patients' backgrounds, institutional ECMO experience, and timing of treatment initiation and prognosis between February 2020 and November 2021. Prognostic factors were evaluated by Kaplan-Meier analysis and Cox proportional hazards analysis. RESULTS: A total of 9418 patients were ventilated, of whom 1214 (13%) received ECMO. The overall survival rate for ventilated patients was 79%, 65% for those receiving ECMO. There have been five outbreaks in Japan to date. The survival rate of ventilated patients increased from 76% in the first outbreak to 84% in the fifth outbreak (p < 0.001). The survival rate of ECMO patients remained unchanged at 60-68% from the first to fifth outbreaks (p = 0.084). Age of ≥ 59 (hazard ratio [HR] 2.17; 95% confidence interval [CI] 1.76-2.68), ventilator days of ≥ 3 before starting ECMO (HR 1.91; 95% CI 1.57-2.32), and institutional ECMO experiences of ≥ 11 (HR 0.70; 95% CI 0.58-0.85) were independent prognostic factors for ECMO. CONCLUSIONS: During five COVID-19 outbreaks in Japan, the survival rate of ventilated patients tended to have gradually improved, and that of ECMO patients did not deteriorate. Older age, longer ventilator days before starting ECMO, and fewer institutional ECMO experiences may be independent prognostic factors for critical COVID-19 patients receiving ECMO.

Prevalence and Risk Factor Analysis of Post-Intensive Care Syndrome in Patients with COVID-19 Requiring Mechanical Ventilation: A Multicenter Prospective Observational Study.

INTRODUCTION: Post-intensive care syndrome (PICS) is an emerging problem in critically ill patients and the prevalence and risk factors are unclear in patients with severe coronavirus disease 2019 (COVID-19). This multicenter prospective observational study aimed to investigate the prevalence and risk factors of PICS in ventilated patients with COVID-19 after ICU discharge. METHODS: Questionnaires were administered twice in surviving patients with COVID-19 who had required mechanical ventilation, concerning Barthel Index, Short-Memory Questionnaire, and Hospital Anxiety and Depression Scale scores. The risk factors for PICS were examined using a multivariate logistic regression analysis. RESULTS: The first and second PICS surveys were obtained at 5.5 and 13.5 months (mean) after ICU discharge, with 251 and 209 patients completing the questionnaires and with a prevalence of PICS of 58.6% and 60.8%, respectively, along with the highest percentages of cognitive impairment. Delirium (with an odds ratio of (OR) 2.34, 95% CI 1.1-4.9, and p = 0.03) and the duration of mechanical ventilation (with an OR of 1.29, 95% CI 1.05-1.58, and p = 0.02) were independently identified as the risk factors for PICS in the first PICS survey. CONCLUSION: Approximately 60% of the ventilated patients with COVID-19 experienced persistent PICS, especially delirium, and required longer mechanical ventilation.

Neutralizing Type I Interferon Autoantibodies in Japanese Patients with Severe COVID-19.

PURPOSE: Autoantibodies (aAbs) to type I interferons (IFNs) have been found in less than 1% of individuals under the age of 60 in the general population, with the prevalence increasing among those over 65. Neutralizing autoantibodies (naAbs) to type I IFNs have been found in at least 15% of patients with life-threatening COVID-19 pneumonia in several cohorts of primarily European descent. We aimed to evaluate the prevalence of aAbs and naAbs to IFN-α2 or IFN-ω in Japanese patients who suffered from COVID-19 as well as in the general population. METHODS: Patients who suffered from COVID-19 (n = 622, aged 0-104) and an uninfected healthy control population (n = 3,456, aged 20-91) were enrolled in this study. The severities of the COVID-19 patients were as follows: critical (n = 170), severe (n = 235), moderate (n = 112), and mild (n = 105). ELISA and ISRE reporter assays were used to detect aAbs and naAbs to IFN-α2 and IFN-ω using E. coli-produced IFNs. RESULTS: In an uninfected general Japanese population aged 20-91, aAbs to IFNs were detected in 0.087% of individuals. By contrast, naAbs to type I IFNs (IFN-α2 and/or IFN-ω, 100 pg/mL) were detected in 10.6% of patients with critical infections, 2.6% of patients with severe infections, and 1% of patients with mild infections. The presence of naAbs to IFNs was significantly associated with critical disease (P = 0.0012), age over 50 (P = 0.0002), and male sex (P = 0.137). A significant but not strong correlation between aAbs and naAbs to IFN-α2 existed (r = - 0.307, p value < 0.0001) reinforced the importance of measuring naAbs in COVID-19 patients, including those of Japanese ancestry. CONCLUSION: In this study, we revealed that patients with pre-existing naAbs have a much higher risk of life-threatening COVID-19 pneumonia in Japanese population.

Relation between nutrition therapy in the acute phase and outcomes of ventilated patients with COVID-19 infection: a multicenter prospective observational study.

BACKGROUND: Optimal nutrition therapy has not yet been established for the acute phase of severe coronavirus disease 2019 (COVID-19) infection. OBJECTIVES: We aimed to examine the effects of nutrition delivery in the acute phase on mortality and the long-term outcomes of post-intensive care syndrome (PICS). METHODS: A multicenter prospective study was conducted on adult patients with COVID-19 infection requiring mechanical ventilation during an intensive care unit (ICU) stay. Daily total energy (kcal/kg) and protein (g/kg) deliveries in the first week of the ICU stay were calculated. The questionnaire for PICS evaluation was mailed within a median of 6 mo after hospital discharge. The primary outcome was in-hospital mortality, and secondary outcomes were the PICS components of physical impairment, cognitive dysfunction, and mental illness. RESULTS: Among 414 eligible patients, 297 who received mechanical ventilation for 7 d or longer were examined. PICS was evaluated in 175 patients among them. High protein delivery on days 4-7 correlated with a low in-hospital mortality rate. In contrast, high protein delivery on days 1-3 correlated with physical impairment. A multivariate logistic regression analysis adjusted for age, sex, BMI, and severity revealed that average energy and protein deliveries on days 4-7 correlated with decreased in-hospital mortality (OR: 0.94; 95% CI: 0.89, 0.99; P = 0.013 and OR: 0.40; 95% CI: 0.17, 0.93; P = 0.031, respectively). Nutrition delivery did not correlate with PICS outcomes after adjustments. In the multivariate regression using a restricted cubic spline model, in-hospital mortality monotonically decreased with increases in average nutrition delivery on days 4-7. CONCLUSIONS: In patents with COVID-19 on mechanical ventilation for ≥7 d, nutrition delivery in the late period of the acute phase was monotonically associated with a decrease in in-hospital mortality. Adequate protein delivery is needed on days 4-7.This trial was registered at https://www.umin.ac.jp as UMIN000041276.

Impact of renin-angiotensin-aldosterone system inhibition on mortality in critically ill COVID-19 patients with pre-existing hypertension: a prospective cohort study.

BACKGROUND: The influence of renin-angiotensin-aldosterone system (RAAS) inhibitors on the critically ill COVID-19 patients with pre-existing hypertension remains uncertain. This study examined the impact of previous use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on the critically ill COVID-19 patients. METHODS: Data from an international, prospective, observational cohort study involving 354 hospitals spanning 54 countries were included. A cohort of 737 COVID-19 patients with pre-existing hypertension admitted to intensive care units (ICUs) in 2020 were targeted. Multi-state survival analysis was performed to evaluate in-hospital mortality and hospital length of stay up to 90 days following ICU admission. RESULTS: A total of 737 patients were included-538 (73%) with pre-existing hypertension had received ACEi/ARBs before ICU admission, while 199 (27%) had not. Cox proportional hazards model showed that previous ACEi/ARB use was associated with a decreased hazard of in-hospital death (HR, 0.74, 95% CI 0.58-0.94). Sensitivity analysis adjusted for propensity scores showed similar results for hazards of death. The average length of hospital stay was longer in ACEi/ARB group with 21.2 days (95% CI 19.7-22.8 days) in ICU and 6.7 days (5.9-7.6 days) in general ward compared to non-ACEi/ARB group with 16.2 days (14.1-18.6 days) and 6.4 days (5.1-7.9 days), respectively. When analysed separately, results for ACEi or ARB patient groups were similar for both death and discharge. CONCLUSIONS: In critically ill COVID-19 patients with comorbid hypertension, use of ACEi/ARBs prior to ICU admission was associated with a reduced risk of in-hospital mortality following adjustment for baseline characteristics although patients with ACEi/ARB showed longer length of hospital stay. Clinical trial registration The registration number: ACTRN12620000421932; The date of registration: 30, March 2020; The URL of the registration: https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12620000421932 .

Post-Intensive Care Syndrome and Its New Challenges in Coronavirus Disease 2019 (COVID-19) Pandemic: A Review of Recent Advances and Perspectives.

Intensive care unit survivors experience prolonged physical impairments, cognitive impairments, and mental health problems, commonly referred to as post-intensive care syndrome (PICS). Previous studies reported the prevalence, assessment, and prevention of PICS, including the ABCDEF bundle approach. Although the management of PICS has been advanced, the outbreak of coronavirus disease 2019 (COVID-19) posed an additional challenge to PICS. The prevalence of PICS after COVID-19 extensively varied with 28-87% of cases pertaining to physical impairments, 20-57% pertaining to cognitive impairments, and 6-60% pertaining to mental health problems after 1-6 months after discharge. Each component of the ABCDEF bundle is not sufficiently provided from 16% to 52% owing to the highly transmissible nature of the virus. However, new data are emerging about analgesia, sedation, delirium care, nursing care, early mobilization, nutrition, and family support. In this review, we summarize the recent data on PICS and its new challenge in PICS after COVID-19 infection.

Establishment of a Disaster Management-like System for COVID-19 Patients Requiring Veno-Venous Extracorporeal Membrane Oxygenation in Japan.

The coronavirus disease 2019 (COVID-19) pandemic has increased the number of patients who require extracorporeal membrane oxygenation (ECMO). To manage the demand for ECMO, Japan ECMOnet for COVID-19 was developed as a "disaster management-like system", utilizing the Cross ICU Searchable Information System (CRISIS) database. This study investigated the effect of the establishment of this disaster management-like system in Japan. This was a nationwide retrospective observational study conducted from 1 February to 31 July in 2020. A total of 187 patients with COVID-19 who received ECMO were included. The median age was 60 years (interquartile range, 53-68), the median length of ventilatory support before ECMO was 3 days (1-5), and the median PaO2 to FiO2 ratio at ECMO initiation was 86 (71.3-101.5). During the study period, 165 telephone consultations were conducted, including general questions about ECMO. Among them, 44 concerned patients who were already on ECMO or who ultimately received ECMO. Further coordination, including transport and ECMO physician dispatch, was provided for 23 cases. Overall, 125/187 (66.8%) patients were successfully weaned from ECMO. This study demonstrated that Japan has achieved favorable survival outcomes for patients with COVID-19 who received ECMO with a disaster management-like system. Further research on the causes of these outcomes is needed.

Oxygen administration for patients with ARDS.

Acute respiratory distress syndrome (ARDS) is a fatal condition with insufficiently clarified etiology. Supportive care for severe hypoxemia remains the mainstay of essential interventions for ARDS. In recent years, adequate ventilation to prevent ventilator-induced lung injury (VILI) and patient self-inflicted lung injury (P-SILI) as well as lung-protective mechanical ventilation has an increasing attention in ARDS.Ventilation-perfusion mismatch may augment severe hypoxemia and inspiratory drive and consequently induce P-SILI. Respiratory drive and effort must also be carefully monitored to prevent P-SILI. Airway occlusion pressure (P0.1) and airway pressure deflection during an end-expiratory airway occlusion (Pocc) could be easy indicators to evaluate the respiratory drive and effort. Patient-ventilator dyssynchrony is a time mismatching between patient's effort and ventilator drive. Although it is frequently unrecognized, dyssynchrony can be associated with poor clinical outcomes. Dyssynchrony includes trigger asynchrony, cycling asynchrony, and flow delivery mismatch. Ventilator-induced diaphragm dysfunction (VIDD) is a form of iatrogenic injury from inadequate use of mechanical ventilation. Excessive spontaneous breathing can lead to P-SILI, while excessive rest can lead to VIDD. Optimal balance between these two manifestations is probably associated with the etiology and severity of the underlying pulmonary disease.High-flow nasal cannula (HFNC) and non-invasive positive pressure ventilation (NPPV) are non-invasive techniques for supporting hypoxemia. While they are beneficial as respiratory supports in mild ARDS, there can be a risk of delaying needed intubation. Mechanical ventilation and ECMO are applied for more severe ARDS. However, as with HFNC/NPPV, inappropriate assessment of breathing workload potentially has a risk of delaying the timing of shifting from ventilator to ECMO. Various methods of oxygen administration in ARDS are important. However, it is also important to evaluate whether they adequately reduce the breathing workload and help to improve ARDS.