Risk Factors for the Mortality of Patients With Coronavirus Disease 2019 Requiring Extracorporeal Membrane Oxygenation in a Non-Centralized Setting: A Nationwide Study.

BACKGROUND: Limited data are available on the mortality rates of patients receiving extracorporeal membrane oxygenation (ECMO) support for coronavirus disease 2019 (COVID-19). We aimed to analyze the relationship between COVID-19 and clinical outcomes for patients receiving ECMO. METHODS: We retrospectively investigated patients with COVID-19 pneumonia requiring ECMO in 19 hospitals across Korea from January 1, 2020 to August 31, 2021. The primary outcome was the 90-day mortality after ECMO initiation. We performed multivariate analysis using a logistic regression model to estimate the odds ratio (OR) of 90-day mortality. Survival differences were analyzed using the Kaplan-Meier (KM) method. RESULTS: Of 127 patients with COVID-19 pneumonia who received ECMO, 70 patients (55.1%) died within 90 days of ECMO initiation. The median age was 64 years, and 63% of patients were male. The incidence of ECMO was increased with age but was decreased after 70 years of age. However, the survival rate was decreased linearly with age. In multivariate analysis, age (OR, 1.048; 95% confidence interval [CI], 1.010-1.089; P = 0.014) and receipt of continuous renal replacement therapy (CRRT) (OR, 3.069; 95% CI, 1.312-7.180; P = 0.010) were significantly associated with an increased risk of 90-day mortality. KM curves showed significant differences in survival between groups according to age (65 years) (log-rank P = 0.021) and receipt of CRRT (log-rank P = 0.004). CONCLUSION: Older age and receipt of CRRT were associated with higher mortality rates among patients with COVID-19 who received ECMO.

Development of a Novel Biomarker for the Progression of Idiopathic Pulmonary Fibrosis.

The progression of idiopathic pulmonary fibrosis (IPF) is diverse and unpredictable. We identified and validated a new biomarker for IPF progression. To identify a candidate gene to predict progression, we assessed differentially expressed genes in patients with advanced IPF compared with early IPF and controls in three lung sample cohorts. Candidate gene expression was confirmed using immunohistochemistry and Western blotting of lung tissue samples from an independent IPF clinical cohort. Biomarker potential was assessed using an enzyme-linked immunosorbent assay of serum samples from the retrospective validation cohort. We verified that the final candidate gene reflected the progression of IPF in a prospective validation cohort. In the RNA-seq comparative analysis of lung tissues, CD276, COL7A1, CTSB, GLI2, PIK3R2, PRAF2, IGF2BP3, and NUPR1 were up-regulated, and ADAMTS8 was down-regulated in the samples of advanced IPF. Only CTSB showed significant differences in expression based on Western blotting (n = 12; p < 0.001) and immunohistochemistry between the three groups of the independent IPF cohort. In the retrospective validation cohort (n = 78), serum CTSB levels were higher in the progressive group (n = 25) than in the control (n = 29, mean 7.37 ng/mL vs. 2.70 ng/mL, p < 0.001) and nonprogressive groups (n = 24, mean 7.37 ng/mL vs. 2.56 ng/mL, p < 0.001). In the prospective validation cohort (n = 129), serum CTSB levels were higher in the progressive group than in the nonprogressive group (mean 8.30 ng/mL vs. 3.00 ng/mL, p < 0.001). After adjusting for baseline FVC, we found that CTSB was independently associated with IPF progression (adjusted OR = 2.61, p < 0.001). Serum CTSB levels significantly predicted IPF progression (AUC = 0.944, p < 0.001). Serum CTSB level significantly distinguished the progression of IPF from the non-progression of IPF or healthy control.

Obesity Paradox and Functional Outcomes in Sepsis: A Multicenter Prospective Study.

OBJECTIVES: In Asian populations, the correlation between sepsis outcomes and body mass is unclear. A multicenter, prospective, observational study conducted between September 2019 and December 2020 evaluated obesity's effects on sepsis outcomes in a national cohort. SETTING: Nineteen tertiary referral hospitals or university-affiliated hospitals in South Korea. PATIENTS: Adult patients with sepsis ( n = 6,424) were classified into obese ( n = 1,335) and nonobese groups ( n = 5,089). MEASUREMENTS AND RESULTS: Obese and nonobese patients were propensity score-matched in a ratio of 1:1. Inhospital mortality was the primary outcome. After propensity score matching, the nonobese group had higher hospital mortality than the obese group (25.3% vs 36.7%; p < 0.001). The obese group had a higher home discharge rate (70.3% vs 65.2%; p < 0.001) and lower median Clinical Frailty Scale (CFS) (4 vs 5; p = 0.007) at discharge than the nonobese group, whereas the proportion of frail patients at discharge (CFS ≥ 5) was significantly higher in the nonobese group (48.7% vs 54.7%; p = 0.011). Patients were divided into four groups according to the World Health Organization body mass index (BMI) classification and performed additional analyses. The adjusted odds ratio of hospital mortality and frailty at discharge for underweight, overweight, and obese patients relative to normal BMI was 1.25 ( p = 0.004), 0.58 ( p < 0.001), and 0.70 ( p = 0.047) and 1.53 ( p < 0.001), 0.80 ( p = 0.095), and 0.60 ( p = 0.022), respectively. CONCLUSIONS: Obesity is associated with higher hospital survival and functional outcomes at discharge in Asian patients with sepsis.

Geographical Differences of Risk of Asthma and Allergic Rhinitis according to Urban/Rural Area: a Systematic Review and Meta-analysis of Cohort Studies.

Several studies have demonstrated an association between the risk asthma/allergic rhinitis and the environment. However, to date, no systematic review or meta-analysis has investigated these factors. We conducted a systematic review and meta-analysis to assess the association between urban/rural living and the risk of asthma and allergic rhinitis. We searched the Embase and Medline databases for relevant articles and included only cohort studies to observe the effects of time-lapse geographical differences. Papers containing information on rural/urban residence and respiratory allergic diseases were eligible for inclusion. We calculated the relative risk (RR) and 95% confidence interval (CI) using a 2 × 2 contingency table and used random effects to pool data. Our database search yielded 8388 records, of which 14 studies involving 50,100,913 participants were finally included. The risk of asthma was higher in urban areas compared to rural areas (RR, 1.27; 95% CI, 1.12-1.44, p < 0.001), but not for the risk of allergic rhinitis (RR, 1.17; 95% CI, 0.87-1.59, p = 0.30). The risk of asthma in urban areas compared to rural areas was higher in the 0-6 years and 0-18 years age groups, with RRs of 1.21 (95% CI, 1.01-1.46, p = 0.04) and 1.35 (95% CI, 1.12-1.63, p = 0.002), respectively. However, there was no significant difference in the risk of asthma between urban and rural areas for children aged 0-2 years, with a RR of 3.10 (95% CI, 0.44-21.56, p = 0.25). Our study provides epidemiological evidence for an association between allergic respiratory diseases, especially asthma, and urban/rural living. Future research should focus on identifying the factors associated with asthma in children living in urban areas. The review was registered in PROSPERO (CRD42021249578).

Erratum: Correction of Affiliations in the Article "Outcomes of Patients on the Lung Transplantation Waitlist in Korea: A Korean Network for Organ Sharing Data Analysis".

This corrects the article on p. e294 in vol. 37, PMID: 36281485.

Erratum: Correction of Affiliations in the Article "Validity of Outcome Prediction Scoring Systems in Korean Patients with Severe Adult Respiratory Distress Syndrome Receiving Extracorporeal Membrane Oxygenation Therapy".

This corrects the article on p. 932 in vol. 31, PMID: 27247503.

Vasopressor Initiation Within 1 Hour of Fluid Loading Is Associated With Increased Mortality in Septic Shock Patients: Analysis of National Registry Data.

OBJECTIVES: To investigate whether administration of a vasopressor within 1 hour of first fluid loading affected mortality and organ dysfunction in septic shock patients. DESIGN: Prospective, multicenter, observational study. SETTING: Sixteen tertiary or university hospitals in the Republic of Korea. PATIENTS: Patients with septic shock (n = 415) were classified into early and late groups according to whether the vasopressor was initiated within 1 hour of the first resuscitative fluid load. Early (n = 149) patients were 1:1 propensity matched to late (n = 149) patients. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: The median time from the initial fluid bolus to vasopressor was shorter in the early group (0.3 vs 2.3 hr). There was no significant difference in the fluid bolus volume within 6 hours (33.2 vs 35.9 mL/kg) between the groups. The Sequential Organ Failure Assessment score and lactate level on day 3 in the ICU were significantly higher in the early group than that in the late group (Sequential Organ Failure Assessment, 9.2 vs 7.7; lactate level, 2.8 vs 1.7 mmol/L). In multivariate Cox regression analyses, early vasopressor use was associated with a significant increase in the risk of 28-day mortality (hazard ratio, 1.83; 95% CI, 1.26-2.65). CONCLUSIONS: Vasopressor initiation within 1 hour of fluid loading was associated with higher 28-day mortality in patients with septic shock.

Outcomes of Patients on the Lung Transplantation Waitlist in Korea: A Korean Network for Organ Sharing Data Analysis.

BACKGROUND: The demand for lung transplants continues to increase in Korea, and donor shortages and waitlist mortality are critical issues. This study aimed to evaluate the factors that affect waitlist outcomes from the time of registration for lung transplantation in Korea. METHODS: Data were obtained from the Korean Network for Organ Sharing for lung-only registrations between September 7, 2009, and December 31, 2020. Post-registration outcomes were evaluated according to the lung disease category, blood group, and age. RESULTS: Among the 1,671 registered patients, 49.1% had idiopathic pulmonary fibrosis (group C), 37.0% had acute respiratory distress syndrome and other interstitial lung diseases (group D), 7.2% had chronic obstructive pulmonary disease (group A), and 6.6% had primary pulmonary hypertension (group B). Approximately half of the patients (46.1%) were transplanted within 1 year of registration, while 31.8% died without receiving a lung transplant within 1 year of registration. Data from 1,611 patients were used to analyze 1-year post-registration outcomes, which were classified as transplanted (46.1%, n = 743), still awaiting (21.1%, n = 340), removed (0.9%, n = 15), and death on waitlist (31.8%, n = 513). No significant difference was found in the transplantation rate according to the year of registration. However, significant differences occurred between the waitlist mortality rates (P = 0.008) and the still awaiting rates (P = 0.009). The chance of transplantation after listing varies depending on the disease category, blood type, age, and urgency status. Waitlist mortality within 1 year was significantly associated with non-group A disease (hazard ratio [HR], 2.76, P < 0.001), age ≥ 65 years (HR, 1.48, P < 0.001), and status 0 at registration (HR, 2.10, P < 0.001). CONCLUSION: Waitlist mortality is still higher in Korea than in other countries. Future revisions to the lung allocation system should take into consideration the high waitlist mortality and donor shortages.

Performance Changes Following the Revision of Organ Allocation System of Lung Transplant: Analysis of Korean Network for Organ Sharing Data.

BACKGROUND: There is currently a lack of data on the impact of the recent revision of the domestic lung allocation system on transplant performance. METHODS: We conducted a retrospective analysis of transplant candidates and transplant patients registered in Korean Network for Organ Sharing between July 2015 and July 2019. Study periods were classified according to the introduction of the revised lung allocation system as follows: period 1 from July 2015 to June 2017 and period 2 from August 2017 to July 2019. RESULTS: During the study period, a total of 627 patients were on the waiting list, of which 398 lung transplantations were performed. Total waiting list size increased by 98.6%, from 210 in period 1 to 417 in period 2. The number of transplant patients also increased by 32.7%, from 171 in period 1 to 227 in period 2. The number of donors decreased from 1,042 to 878, whereas the usage rate, i.e., the number of lung donors used for transplantation among the total number of reported lung donors, increased from 16.4% to 25.9%. The proportion of patients with high urgent status at transplantation increased from 45% to 60.4%, whereas those with urgent status decreased from 46.8% to 35.7% (P = 0.006). The use of marginal donor lungs increased from 29.8% to 53.7% (P < 0.001). To adjust urgency status and marginal donor usage between two groups, we conducted a propensity score matching analysis. No significant differences were detected in 1-year survival rates between the two periods after propensity score matching. As well, no significant difference was observed in mortality on the waiting list between the two periods. CONCLUSION: The recent revision of the lung allocation system in Korea did not change the performance of lung transplant in terms of waiting list mortality and 1-year survival. The rapid increase in the volume of waiting list between the two periods increased the waiting time, transplantation of high-urgency patients, and use of marginal lung donors.

Chlorhexidine bathing of the exposed circuits in extracorporeal membrane oxygenation: an uncontrolled before-and-after study.

BACKGROUND: Although the prevention of extracorporeal membrane oxygenation (ECMO) catheter-related infection is crucial, scientific evidence regarding best practices are still lacking. METHODS: We conducted an uncontrolled before-and-after study to test whether the introduction of disinfection with 2% chlorhexidine gluconate (CHG) and 70% isopropyl alcohol (IPA) of the exposed circuits and hub in patients treated with ECMO would affect the rate of blood stream infection (BSI) and microbial colonization of the ECMO catheter. We compared the microbiological and clinical data before and after the intervention. RESULTS: A total of 1740 ECMO catheter days in 192 patients were studied. These were divided into 855 ECMO catheter days in 96 patients before and 885 ECMO catheter days in 96 patients during the intervention. The rates of BSI were significantly decreased during the intervention period at 11.7/1000 ECMO catheter days before vs. 2.3/1000 ECMO catheter days during (difference 9.4, 95% confidence interval (CI) 1.5-17.3, p = 0.019). Furthermore, the colonization of the ECMO catheter was similarly significantly reduced during the intervention period at 10.5/1000 ECMO catheter days before vs. 2.3/1000 ECMO catheter days during intervention (difference 8.3, 95% CI 0.7-15.8, p = 0.032). Hospital mortality (41.7% vs. 24%, p = 0.009) and sepsis-related death (17.7% vs. 6.3%, p = 0.014) were also significantly decreased during intervention. CONCLUSION: Extensive disinfection of exposed ECMO circuits and hub with 2% CHG/IPA was associated with a reduction in both BSI and microbial colonization of ECMO catheters. A further randomized controlled study is required to verify these results. TRIAL REGISTRATION: KCT 0004431.

Heart-lung transplantation for refractory diffuse alveolar hemorrhage supported by prolonged extracorporeal membrane oxygenation after cardiogenic shock from ST segment elevation myocardial infarction: a case report.

Diffuse alveolar hemorrhage after percutaneous coronary intervention is a rare but fatal complication. Although timely application of extracorporeal membrane oxygenator and discontinuation of antiplatelet/anticoagulation is the treatment of choice, bleeding is often irreversible. Herein, we introduce a patient with refractory diffuse alveolar hemorrhage after prolonged extracorporeal membrane oxygenator and percutaneous coronary intervention, who was eventually rescued with heart-lung transplantation.

Learning curve for multidisciplinary team setup in veno-venous extracorporeal membrane oxygenation for acute respiratory failure.

BACKGROUND: Quality control is essential for a successful extracorporeal membrane oxygenation program. We investigated the learning curve for outcome improvement and focused on factors associated with failure of extracorporeal membrane oxygenation treatment. METHODS: Between August 2011 and May 2017, 150 patients were supported with veno-venous extracorporeal membrane oxygenation for acute respiratory failure. The learning curve was examined using cumulative sum analysis. We defined successful extracorporeal membrane oxygenation treatment as intensive care unit discharge, acceptable failure rate as 40%, and unacceptable failure rate as 60%. We chronologically divided patients into three periods with 50 consecutive patients each and retrospectively compared the clinical outcomes by period. RESULTS: Overall, weaning and survival to discharge rates were 72.7% and 56%, respectively. Cumulative sum analysis indicated that the extracorporeal membrane oxygenation team achieved nearly acceptable performance after 56 cases and consistently acceptable performance after 104 cases. Clinical outcomes were improved by period: weaning rate (58% vs. 80% vs. 80%, p = 0.017); intensive care unit discharge rate (42% vs. 60% vs. 78%, p = 0.001); survival to discharge rate (40% vs. 58% vs. 70%, p = 0.010); and 1 year survival rate (40% vs. 56% vs. 70%, p = 0.010). In multivariate analysis, infection (odds ratio: 4.54, 95% confidence interval: 1.83-11.27, p = 0.001), immune compromise (odds ratio: 5.78, 95% confidence interval: 1.66-20.14, p = 0.006), extracorporeal membrane oxygenation team period (odds ratio: 2.12, 95% confidence interval: 1.14-3.92, p = 0.017), and age (odds ratio: 1.09, 95% confidence interval: 1.05-1.14, p < 0.001) were associated with extracorporeal membrane oxygenation failure. CONCLUSION: More than 100 cases of extracorporeal membrane oxygenation experience were necessary for acceptable performance and stabilization of outcomes.

Extracorporeal membrane oxygenation for life-threatening asthma refractory to mechanical ventilation: analysis of the Extracorporeal Life Support Organization registry.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) in cases of near-fatal asthma (NFA) has increased, but the benefits and potential complications of this therapy have yet to be fully investigated. METHODS: Cases were extracted from the Extracorporeal Life Support Organization Registry between March 1992 and March 2016. All patients with a diagnosis of asthma (according to the International Classification of Diseases 9th edition), who also received ECMO, were extracted. Exclusion criteria included patients who underwent multiple courses of ECMO; those who received ECMO for cardiopulmonary resuscitation or cardiac dysfunction; and those with another primary diagnosis, such as sepsis. We analyzed survival to hospital discharge, complications, and clinical factors associated with in-hospital mortality, in patients with severe life-threatening NFA requiring ECMO support. RESULTS: In total 272 patients were included. The mean time spent on ECMO was 176.4 hours. Ventilator settings, including rate, fraction of inspired oxygen (FiO2), peak inspiratory pressure (PIP), and mean airway pressure, significantly improved after ECMO initiation (rate (breaths/min), 19.0 vs. 11.3, p < 0.001; FiO2 (%), 81.2 vs. 48.8, p < 0.001; PIP (cmH2O), 38.2 vs. 25.0, p < 0.001; mean airway pressure (cmH2O): 21.4 vs. 14.2, p < 0.001). In particular, driving pressure was significantly decreased after ECMO support (29.5 vs. 16.8 cmH2O, p < 0.001). The weaning success rate was 86.7%, and the rate of survival to hospital discharge was 83.5%. The total complication rate was 65.1%, with hemorrhagic complications being the most common (28.3%). Other complications included renal (26.8%), cardiovascular (26.1%), mechanical (24.6%), metabolic (22.4%), infection (16.5%), neurologic (4.8%), and limb ischemia (2.6%). Of the hemorrhagic complications, cannulation site hemorrhage was the most common (13.6%). Using multivariate logistic regression analysis, it was found that hemorrhage was associated with increased in-hospital mortality (odds ratio, 2.97; 95% confidence interval, 1.07-8.24; p = 0.036). Hemorrhage-induced death occurred in four patients (1.5%). The most common reason for death was organ failure (37.8%). CONCLUSIONS: ECMO can provide adequate gas exchange and prevent lung injury induced by mechanical ventilation, and may be an effective bridging strategy to avoid aggressive ventilation in refractory NFA. However, careful management is required to avoid complications.

Current Status and Future of Lung Donation in Korea.

Lung transplantation is the only effective treatment option for patients with end-stage lung disease. However, donor organ shortage makes timely transplant not possible for all patients, especially in Korea. We investigated the number and utilization of donor lungs by retrospectively reviewing all donor organs registered in the Korea Network for Organ Sharing database from March 2012 to March 2016. The donors were stratified into 4 groups by donor acceptability criteria. A total of 1,304 donors were included. Of those, 295 brain-dead donors (22.6%) consented to lung donation. Among these consented donors, 168 donors (12.9%) were retrieved for lung transplant. Retrieval rate was very low compared with that of the kidney (93.9%), liver (86.3%), and heart (27.3%). The characteristics of utilized donor lungs were: mean age, 40.5 years (range: 18 to 63 years); mean partial pressure of oxygen, 356.5 mmHg; mean smoking history, 5.9 pack-years; and mean body mass index, 22.6 kg/m². The proportion of donors with acceptable condition of the transplanted lungs was only 39.3% (ideal 19, standard 47, marginal 70, unusable 32). Among brain-dead patients who denied to donate lungs (n = 1,009), 82 were potentially acceptable donors (ideal 19, standard 63), which was equal to half of actually transplanted lung donations. Many potential donor lungs, which are currently excluded, may be successfully used in lung transplantation in Korea. The available lung donors must be actively selected and managed to maximize the utilization of this precious resource.

The Utility of Preemptive Distal Perfusion Cannulation During Peripheral Venoarterial Extracorporeal Membrane Oxygenation Support.

OBJECTIVES: We compared the ischemia and rescue rates according to the strategy of distal cannulation. BACKGROUND: Limb ischemia developing during percutaneous venoarterial (VA) extracorporeal membrane oxygenation (ECMO) is a potentially severe complication. Although appropriate use of a distal perfusion cannula can avoid ischemia, evidences about distal cannulation is still lacking. METHODS: Patients who underwent peripheral VA ECMO between January 2010 and August 2015 were reviewed. We classified patients into 2 groups in terms of insertion timing with respect to the onset of ischemia. The preemptive strategy group underwent early insertion of a distal perfusion cannula at commencement of ECMO support. The rescue strategy group underwent delayed cannula insertion after onset of limb ischemia. RESULTS: A total of 151 patients were included in the analysis. Forty-four patients formed the preemptive strategy group and 107 patients formed the rescue strategy group. In total, 10 of 151 (6.7%) patients developed significant limb ischemia, they all were the rescue strategy group (10/107, 9.3%). Of the 10 patients, 2 patients were rescued from limb ischemia after distal cannulation. Otherwise, ischemia was not rescued in the remaining eight patients. Of the latter 8, 3 patient required surgical interventions (2 fasciotomy and 1 below-the-knee amputation) and the other five died from disease aggravation prior to surgical intervention. CONCLUSIONS: Preemptive distal perfusion cannulation is safe and effective when used to prevent lower limb ischemia in patients undergoing femoral cannulation to treat ECMO. However, delayed distal cannulation increases the extent of cannulation site bleeding, without improving the ischemia.

Impact of bloodstream infections on catheter colonization during extracorporeal membrane oxygenation.

There are concerns about secondary extracorporeal membrane oxygenation (ECMO) catheter infections in bacteremic patients. We investigated the association between blood stream infection (BSI) and ECMO catheter colonization. From January 2012 to August 2014, 47 adults who received ECMO support were enrolled. The ECMO catheter tip was cultured at the end of the ECMO procedure. The enrolled patients were classified into two groups according to the presence of BSI during ECMO support and analyzed with respect to ECMO catheter colonization. Of 47 cases, BSI during ECMO was identified in 13 patients (27.7 %). ECMO catheter colonization was identified in 6 (46.2 %) patients in the BSI group and 3 (8.8 %) in the non-BSI group. BSI during ECMO support was independently associated with ECMO catheter colonization [odds ratio (OR) 5.55; 95 % confidence interval (CI) 1.00-30.73; p = 0.049]. The organisms colonizing ECMO catheters in the setting of primary BSI were predominantly Gram-positive cocci and Candida species. Acinetobacter baumannii was the most common colonizing pathogen in the setting of secondary BSI. All the organisms colonizing ECMO catheters were multi-drug resistant organisms, including methicillin-resistant S. aureus, Candida glabrata, and carbapenem-resistant A. baumannii. ECMO catheters may become contaminated with multi-drug resistant pathogens in the presence of BSI. Therefore, ECMO should be applied cautiously in septic patients with bacteremia caused by multi-drug resistant pathogens.