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.

Extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis.

BACKGROUND: There are several reports of extracorporeal membrane oxygenation (ECMO) use in patients with coronavirus disease 2019 (COVID-19) who develop severe acute respiratory distress syndrome (ARDS). We conducted a systematic review and meta-analysis to guide clinical decision-making and future research. METHODS: We searched MEDLINE, Embase, Cochrane and Scopus databases from 1 December 2019 to 10 January 2021 for observational studies or randomised clinical trials examining ECMO in adults with COVID-19 ARDS. We performed random-effects meta-analyses and meta-regression, assessed risk of bias using the Joanna Briggs Institute checklist and rated the certainty of evidence using the GRADE approach. Survival outcomes were presented as pooled proportions while continuous outcomes were presented as pooled means, both with corresponding 95% confidence intervals [CIs]. The primary outcome was in-hospital mortality. Secondary outcomes were duration of ECMO therapy and mechanical ventilation, weaning rate from ECMO and complications during ECMO. RESULTS: We included twenty-two observational studies with 1896 patients in the meta-analysis. Venovenous ECMO was the predominant mode used (98.6%). The pooled in-hospital mortality in COVID-19 patients (22 studies, 1896 patients) supported with ECMO was 37.1% (95% CI 32.3-42.0%, high certainty). Pooled mortality in the venovenous ECMO group was 35.7% (95% CI 30.7-40.7%, high certainty). Meta-regression found that age and ECMO duration were associated with increased mortality. Duration of ECMO support (18 studies, 1844 patients) was 15.1 days (95% CI 13.4-18.7). Weaning from ECMO (17 studies, 1412 patients) was accomplished in 67.6% (95% CI 50.5-82.7%) of patients. There were a total of 1583 ECMO complications reported (18 studies, 1721 patients) and renal complications were the most common. CONCLUSION: The majority of patients received venovenous ECMO support for COVID-19-related ARDS. In-hospital mortality in patients receiving ECMO support for COVID-19 was 37.1% during the first year of the pandemic, similar to those with non-COVID-19-related ARDS. Increasing age was a risk factor for death. Venovenous ECMO appears to be an effective intervention in selected patients with COVID-19-related ARDS. PROSPERO CRD42020192627.

[Anesthetic Management for Patients with Chronic Obstructive Lung Disease].

The -most common cause of COPD is cigarette smoking. We use mMRD (Modified British Medical Research Council), CAT (COPD Assessment Test) and GOLD classification of airflow limitation, to evaluate severity of patients with COPD before surgery and create plans to manage their anesthesia. Known COPD is an important patient-related risk factor for postoperative pulmonary complications. Relative risks of postoperative pulmonary complications have ranged from 2.7 to 6.0. Cessation of smoking for four to eight weeks prior to surgery decreases risk of postoperative pulmonary complications. Preoperative instruction regarding inspiratory muscle training may be accomplished. This strategy is time-intensive and potentially expensive. We suggest monitored anesthesia care (MAC), neuraxial anesthesia, or other regional anesthetic tech- niques, but MAC and neuraxial or peripheral regional anesthetic techniques are not suitable for some patients. Non-invasive ventilation (NIV) should be readily available in the postanesthesia care unit to treat respiratory distress in COPD patients.

The Association of Fever with Total Mechanical Ventilation Time in Critically Ill Patients.

This research aims to investigate the impact of fever on total mechanical ventilation time (TVT) in critically ill patients. Subgroup analysis was conducted using a previous prospective, multicenter observational study. We included mechanically ventilated patients for more than 24 hours from 10 Korean and 15 Japanese intensive care units (ICU), and recorded maximal body temperature under the support of mechanical ventilation (MAX(MV)). To assess the independent association of MAX(MV) with TVT, we used propensity-matched analysis in a total of 769 survived patients with medical or surgical admission, separately. Together with multiple linear regression analysis to evaluate the association between the severity of fever and TVT, the effect of MAX(MV) on ventilator-free days was also observed by quantile regression analysis in all subjects including non-survivors. After propensity score matching, a MAX(MV) ≥ 37.5°C was significantly associated with longer mean TVT by 5.4 days in medical admission, and by 1.2 days in surgical admission, compared to those with MAX(MV) of 36.5°C to 37.4°C. In multivariate linear regression analysis, patients with three categories of fever (MAX(MV) of 37.5°C to 38.4°C, 38.5°C to 39.4°C, and ≥ 39.5°C) sustained a significantly longer duration of TVT than those with normal range of MAX(MV) in both categories of ICU admission. A significant association between MAX(MV) and mechanical ventilator-free days was also observed in all enrolled subjects. Fever may be a detrimental factor to prolong TVT in mechanically ventilated patients. These findings suggest that fever in mechanically ventilated patients might be associated with worse mechanical ventilation outcome.

[ECMO for the patients with severe respiratory failure associated with ARDS due to influenza].

Although the survival rate of H1N1-related severe respiratory failure following ECMO therapy was high in several countries, the rate in Japan has been low. Efforts should be made to supply suitable equipments, to train the physicians, and to establish transport system for the patient.

Multisystem inflammatory syndrome in adults with COVID-19 requiring mechanical ventilation: A retrospective cohort study.

Aim: Multisystem inflammatory syndrome in adults (MIS-A) is a hyperinflammatory multisystem condition associated with coronavirus disease (COVID-19). Critically ill COVID-19 patients may develop multiorgan damage and elevated inflammatory responses, thus making it difficult to differentiate between progression to organ damage due to COVID-19 itself or MIS-A. This study aimed to explore the characteristics and complications of MIS-A in critical COVID-19 patients. Methods: The Japan Extracorporeal Membrane Oxygenation (ECMO) Network and ICU Collaboration Network developed a web-based database system called the CRoss Intensive Care Unit Searchable Information System (CRISIS) to monitor critical COVID-19 patients throughout Japan. We retrospectively identified patients with MIS-A among critical COVID-19 patients enrolled from March 2020 to December 2021, using CRISIS. Our MIS-A definition required patients to be at least 18 years of age, have laboratory evidence of inflammation, severe dysfunction of at least two extrapulmonary organ systems, and no plausible alternative diagnoses. Results: Of the 1052 patients, 26 (2.5%) were diagnosed with MIS-A. The MIS-A patients had a higher likelihood of using ECMO (13% vs. 46%, p < 0.001) and lower overall survival (77% vs. 42%, p < 0.001) than non-MIS-A patients. More than 80% of the MIS-A cases occurred 3 weeks after the COVID-19 onset. Conclusion: Multisystem inflammatory syndrome in adults can occur in 2.5% of critically ill COVID-19 patients, and the mortality rate is high. Multisystem inflammatory syndrome in adults may be considered when there is a re-elevation of the unexplained inflammatory response and severe dysfunction of at least two extrapulmonary organ systems several weeks after the onset of COVID-19.

Noninvasive ventilation in pulmonary edema complicating acute myocardial infarction.

BACKGROUND: Because it remains unclear whether noninvasive ventilation (NIV) is an effective therapy for cardiogenic pulmonary edema secondary to acute myocardial infarction (AMI), we retrospectively evaluated our experience with NIV in the treatment of pulmonary edema secondary to AMI and other cardiac conditions. METHODS AND RESULTS: The study group included 206 patients with cardiogenic pulmonary edema, divided into an AMI group (53 patients) and a non-AMI group (153 patients). The weaning rate from NIV was similar in the AMI and non-AMI groups (90.6% vs. 90.8%, P=0.950). Heart rate, blood pressure, and respiratory rate decreased significantly 1h after initiation of NIV in both groups, and were maintained until weaning from NIV. The frequency of endotracheal intubation after weaning from NIV was higher in the AMI group than in the non-AMI group (7.5% vs. 0.7%, P=0.016), although the overall frequency of intubation was similar in both groups. The in-hospital mortality rate was similar in the AMI and non-AMI groups (13.1% vs. 9.8%, P=0.489). CONCLUSIONS: NIV effectively improved vital signs and oxygenation and lowered the intubation rate in patients with cardiogenic pulmonary edema of all etiologies, including AMI. The outcome in patients with AMI treated with NIV depends primarily on the severity of the course of AMI and not on the severity of acute respiratory failure.

Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study.

INTRODUCTION: Fever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness. METHODS: We designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring >48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAXICU) and the use of antipyretic treatments with 28-day mortality. RESULTS: We recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P=0.028, acetaminophen: 2.05, P=0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P=0.15, acetaminophen: 0.58, P=0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAXICU ≥ 39.5°C increased risk of 28-day mortality in non-septic patients (adjusted odds ratio 8.14, P=0.01), but not in septic patients (adjusted odds ratio 0.47, P=0.11) [corrected]. CONCLUSIONS: In non-septic patients, high fever (≥39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00940654.

A case of rapid diagnosis of Boerhaave syndrome by thoracic drainage.

BACKGROUND: Boerhaave syndrome is a rare and often fatal syndrome. Delayed diagnosis and treatment is closely associated with prolonged morbidity and increased mortality. In general, esophagography is usually chosen as the diagnostic procedure, but it has a relatively high false-negative rate. There are no reports, to our knowledge, regarding the efficacy of thoracic drainage, although it is easier to perform and more immediate than esophagography in the emergency department. OBJECTIVES: To report the efficacy of thoracic drainage for rapid diagnosis and treatment of Boerhaave syndrome. CASE REPORT: An 80-year-old woman was admitted with vomiting and sudden onset of postprandial chest pain radiating to the back. Initially, myocardial infarction or aortic dissection was suspected, but was excluded by point-of-care tests and computed tomography (CT) scan, which revealed a left-sided pneumothorax, heterogeneous left pleural effusion, and pneumomediastinum at the lower level of the esophagus. Boerhaave syndrome was suspected and confirmed by thoracic drainage, which drained off bloody fluid and residual food such as broccoli. Emergency thoracotomy was performed within 4 h after onset of symptoms. The patient made an uneventful recovery. CONCLUSION: Findings in this case indicate that chest pain, left-sided massive effusion on chest radiography, and left-sided massive heterogeneous effusion on CT scan are important for the diagnosis of Boerhaave syndrome. Subsequent thoracic drainage is useful for confirming Boerhaave syndrome, and such a strategy might lead to a good prognosis for patients with this rare but critical disease.

Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) severe respiratory failure in Japan.

PURPOSE: To evaluate procedures and outcomes of extracorporeal membrane oxygenation (ECMO) therapy applied to 2009 influenza A(H1N1) severe respiratory failure patients in Japan. METHODS: This observational study used database information about adults who received ECMO therapy for H1N1-related severe respiratory failure from April 1, 2010 to March 31, 2011. RESULTS: Fourteen patients from 12 facilities were enrolled. Anti-influenza drugs were used in all cases. Before the start of ECMO, the lowest PaO(2)/FiO(2) was median (interquartile) of 50 (40-55) mmHg, the highest peak inspiratory pressure was 30 (29-35) cmH(2)O, and mechanical ventilation had been applied for at least 7 days in 5 patients. None of the facilities had extensive experience with ECMO for respiratory failure (6 facilities, no previous experience; 5 facilities, one or two cases annually). The blood drainage cannula was smaller than 20 Fr. in 10 patients (71.4 %). The duration of ECMO was 8.5 (4.0-10.8) days. The duration of each circuit was only 4.0 (3.2-5.3) days, and the ECMO circuit had to be renewed 19 times (10 cases). Thirteen patients (92.9 %) developed adverse events associated with ECMO, such as oxygenator failure, massive bleeding, and disseminated intravascular coagulation. The survival rate was 35.7 % (5 patients). CONCLUSION: ECMO therapy for H1N1-related severe respiratory failure in Japan has very poor outcomes, and most patients developed adverse events. However, this result does not refute the effectiveness of ECMO. One possible cause of these poor outcomes is the lack of satisfactory equipment, therapeutic guidelines, and systems for patient transfer to central facilities.

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.

Noninvasive positive pressure ventilation in patients with perioperative negative pressure pulmonary edema.

Negative pressure pulmonary edema (NPPE) is a noncardiogenic pathological process that is treated with invasive ventilation via a tracheal tube. To investigate the feasibility and safety of noninvasive positive pressure ventilation (NPPV) as an alternative treatment for NPPE, we retrospectively reviewed charts of 15 perioperative NPPE patients. Eight patients were treated by NPPV and 7 were treated by invasive ventilation. Patient characteristics, duration of NPPV, duration of intensive care unit (ICU) stay, and maximum airway pressure were investigated for the NPPV-treated patients. All patients treated by NPPV had a patent airway after complete relief of the airway obstruction and recovered from NPPE symptoms within one postoperative day. Arterial blood gas analysis showed a significant improvement in the PaO(2)/FiO(2) ratio from 132 + or - 30 mmHg in the operating room to 282 + or - 77 mmHg at discontinuation of NPPV. Serious complications, such as ventilator-associated pneumonia or aspiration pneumonia, did not occur, and intubation was not required for any patient. Favorable outcomes in these cases suggest that NPPV could be a feasible and safe alternative for treating NPPE if the patency of the airway is restored.

Veno-venous extracorporeal membrane oxygenation and prone ventilation for therapeutic management of COVID-19.

BACKGROUND: The efficacy and safety of the combined use of veno-venous extracorporeal membrane oxygenation (ECMO) and prone ventilation are currently not known for coronavirus disease 2019 (COVID-19). CASE PRESENTATION: We report two cases in which the combination of veno-venous ECMO and prone ventilation for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia were successfully carried out. Both patients had developed severe respiratory failure due to SARS-CoV-2 pneumonia, thus requiring veno-venous ECMO. Prone ventilation was also administered safely. CONCLUSION: Oxygenation and lung compliance gradually improved during prone ventilation, and both patients were successfully extubated. For patients with severe SARS-CoV-2 pneumonia who require veno-venous ECMO, the use of prone ventilation could be beneficial, and should be considered.

Postoperative intensive care unit drug fever caused by dexmedetomidine.

Dexmedetomidine hydrochloride is a potent, highly selective alpha-2 adrenergic receptor agonist, broadly used as a sedative drug in intensive care units. We describe the case of a 59-yr-old patient who experienced drug fever caused by dexmedetomidine hydrochloride. The patient was transferred to the intensive care unit with an abdominal aortic aneurysm rupture. After initiation of sedation with dexmedetomidine hydrochloride, he developed pyrexia of more than 39 degrees C. This symptom improved rapidly 7 h after stopping dexmedetomidine hydrochloride. Other possible causes (such as infection) were sequentially eliminated.

The efficacy of dexmedetomidine in patients with noninvasive ventilation: a preliminary study.

BACKGROUND: Agitation is associated with failure of noninvasive ventilation (NIV). We investigated the effect of dexmedetomidine in patients with NIV. METHODS: This was a prospective clinical investigation in an intensive care unit. Dexmedetomidine was infused in 10 patients in whom NIV was difficult because of agitation. RESULTS: Ramsay and Richmond Agitation-Sedation Scale scores were maintained at 2.94 +/- 0.94 and -1.23 +/- 1.30, respectively. All patients were successfully weaned from NIV, and the respiratory state was not worsened. CONCLUSION: This study shows that dexmedetomidine is an effective sedative drug for patients with NIV.

Comparison of extracorporeal membrane oxygenation outcome for influenza-associated acute respiratory failure in Japan between 2009 and 2016.

BACKGROUND: Since the 2009 pandemic influenza, we have nationally established a committee of the extracorporeal membrane oxygenation (ECMO) project. This project involves adequate respiratory management for severe respiratory failure using ECMO. This study aimed to investigate the correlations between changes in respiratory management using ECMO in Japan and outcomes of patients with influenza-associated acute respiratory failure between 2009 and 2016. METHODS: We investigated the incidence, severity, characteristics, and prognosis of influenza-associated acute respiratory failure in 2016 by web-based surveillance. The correlations between clinical characteristics, ventilator settings, ECMO settings, and prognosis were evaluated. RESULTS: A total of 14 patients were managed with ECMO in 2016. There were no significant differences in age, sex, and the acute physiology and chronic health evaluation II score between 2009 and 2016. The maximum sequential organ failure assessment score and highest positive end-expiratory pressure were lower in 2016 than in 2009 (p = 0.03 and p = 0.015, respectively). Baseline and lowest partial pressure of arterial oxygen (PaO2)/fraction of inspiratory oxygen (FIO2) ratios were higher in 2016 than in 2009 (p = 0.009 and p = 0.002, respectively). The types of consoles, circuits, oxygenators, centrifugal pumps, and cannulas were significantly changed between 2016 and 2009 (p = 0.006, p = 0.003, p = 0.004, p < 0.001, respectively). Duration of the use of each circuit was significantly longer in 2016 than in 2009 (8.5 vs. 4.0 days; p = 0.0001). Multivariate analysis showed that the use of ECMO in 2016 was an independent predictor of better overall survival in patients with influenza-associated acute respiratory failure (hazard ratio, 7.25; 95% confidence interval, 1.35-33.3; p = 0.021). CONCLUSIONS: Respiratory management for influenza-associated acute respiratory failure using ECMO was significantly changed in 2016 compared with 2009 in Japan. The outcome of ECMO use had improved in 2016 compared with the outcome in 2009 in patients with influenza-associated acute respiratory failure.

Repair of an infrarenal abdominal aortic aneurysm is associated with persistent left ventricular diastolic dysfunction.

BACKGROUND: Left ventricular (LV) diastolic function has received much attention recently. However, few studies have evaluated LV diastolic function in the perioperative period. The aim of this study was to elucidate perioperative changes in diastolic function using tissue Doppler imaging (TDI) in patients undergoing repair of an infrarenal abdominal aortic aneurysm (AAA). METHODS: Eight patients undergoing repair of an infrarenal AAA were studied prospectively using transesophageal echocardiography. Doppler echocardiographic examinations were performed before the surgical procedure (T1), immediately before aortic unclamping (T2), 30 minutes after aortic unclamping (T3), and at the end of surgery (T4). RESULTS: Pulmonary edema developed in two patients on postoperative day 1. These two patients had the lowest early diastolic mitral annular velocity (Ea) of the study group at the end of surgery. The ratio of the peak velocity of early mitral inflow (E) to the peak velocity of atrial inflow was significantly decreased at T3 and T4. The systolic ejection velocity was significantly decreased at T3, but returned to the baseline value at T4. The Ea was significantly decreased at T3 and T4. The E/Ea ratio showed a progressive rise and was significantly increased at T3 and T4. CONCLUSIONS: In patients undergoing repair of an infrarenal AAA, the Ea derived using TDI decreases at T3 and is still reduced at T4. The E/Ea ratio, which is used to estimate LV filling pressures, is significantly increased at T3 and T4. Further research is required to confirm the development of diastolic dysfunction and determine its possible association with increased postoperative morbidity and mortality.