A Pilot Estimation of Ventricular-Arterial Coupling Using a Vascular Screening Device (VaSera®).

BACKGROUND: Non-invasive cardiovascular assessment has become an alternative to invasive techniques. VaSera®, a vascular screening device, measures arterial stiffness with the cardio-ankle vascular index (CAVI); it also measures cardiophysiological variables of ejection time (ET) and pre-ejection period (PEP). We aimed to apply the parameters obtained by VaSera® to estimate heart function based on left ventricular end-systolic elastance/arterial elastance (Ees/Ea) and to assess the minimal required number of measurements for estimation. METHODS: We conducted an experimental laboratory study for healthy volunteers. Using the previously established formula, the Ees/Ea value of each participant was estimated using ET and PEP values measured by VaSera®. The intraclass correlation coefficient (ICC) assessed the minimum required number of measurements. Concordance correlation coefficient (CCC) and Bland and Altman analysis assessed variation of Ees/Ea estimation against the trimmed average. RESULTS: A total of 660 measurements from 132 participants were included. The Ees/Ea estimates from the VaSera® were 1.5 [1.2, 1.9]. The ICC for Ees/Ea was 0.71 (95% confidence interval: 0.65-0.77), suggesting that four measurements were required. The CCC between the trimmed average of Ees/Ea and the mean of four Ees/Ea estimates was 0.99. Bland and Altman analysis showed excellent agreement for the mean of four Ees/Ea estimates and the trimmed average of Ees/Ea. CONCLUSIONS: For screening of heart failure, the Ees/Ea estimated using non-invasive vascular-stiffness assessment device would be tolerable and four sequential measurements were required.

GENETIC DELETION OF TRANSLOCATOR PROTEIN EXACERBATES POST-SEPSIS SYNDROME WITH ACTIVATION OF THE C1Q PATHWAY IN SEPTIC MOUSE MODEL.

ABSTRACT: Significant numbers of patients who survive sepsis exhibit psychiatric and cognitive impairments, termed post-sepsis syndrome. Understanding the underlying pathophysiology is essential to develop effective therapies. Translocator protein 18 kDa (TSPO) is a multifaceted mitochondrial protein implicated in inflammation, oxidative stress, and steroidogenesis in the central nervous system. Despite accumulated evidence demonstrating TSPO is a biomarker in psychiatric and neurodegenerative disorders, the role of this protein in post-sepsis syndrome remains elusive. The aim of this study was to investigate the role of TSPO in the long-term impairment of mouse behavior associated with psychiatric and cognitive impairments following sepsis induced by cecal ligation and puncture (CLP) surgery. Animals were divided into three groups: (i) wild type (WT) + sham, (ii) WT + CLP, and (iii) TSPO knock out + CLP. Survival rate and body weight change were assessed up to 17 days after surgeries. Then, we also assessed anxiety-like behavior, depression-like behavior, cognitive function, locomotor activity, and forelimb muscle strength in surviving mice by elevated plus maze, tail suspension test, y-maze, open field test, and grip strength test, respectively. Deletion of the TSPO gene led to high mortality and prolonged weight loss and exacerbated anxiety-like and depressive-like behavior with cognitive impairment 17 days after, but not before, CLP surgery. RNA-seq analysis of the hippocampus revealed the upregulation of genes (C1qb, C1qc, and Tyrobp) in C1q complement pathways correlated significantly with anxiety-like behavior that appeared long after CLP surgery. The expressions of these genes predicted other behavioral traits, including depressive-like behavior in the tail suspension test and grip power impairment, supporting the role of the C1q pathway in post-sepsis syndrome. Because the C1q pathway has recently attracted interest as a tag for pathological synaptic elimination, the current study suggests the C1q pathway is involved in the psychiatric and cognitive impairments observed in post-sepsis syndrome.

The association between initial calculated driving pressure at the induction of general anesthesia and composite postoperative oxygen support.

PURPOSE: Early discontinuation of postoperative oxygen support (POS) would partially depend on the innate pulmonary physics. We aimed to examine if the initial driving pressure (dP) at the induction of general anesthesia (GA) predicted POS prolongation. METHODS: We conducted a single-center retrospective study using the facility's database. Consecutive subjects over 2 years were studied to determine the change in odds ratio (OR) for POS prolongation of different dP classes at GA induction. The dP (cmH2O) was calculated as the ratio of tidal volume (mL) over dynamic Crs (mL/cmH2O) regardless of the respiratory mode. The adjusted OR was calculated using the logistic regression model of multivariate analysis. Moreover, we performed a secondary subgroup analysis of age and the duration of GA. RESULTS: We included 5,607 miscellaneous subjects. Old age, high scores of American Society of Anesthesiologist physical status, initial dP, and long GA duration were associated with prolonged POS. The dP at the induction of GA (7.78 [6.48, 9.45] in median [interquartile range]) was categorized into five classes. With the dP group of 6.5-8.3 cmH2O as the reference, high dPs of 10.3-13 cmH2O and ≥ 13 cmH2O were associated with significant prolongation of POS (adjusted OR, 1.62 [1.19, 2.20], p = 0.002 and 1.92 [1.20, 3.05], p = 0.006, respectively). The subgroup analysis revealed that the OR for prolonged POS of high dPs disappeared in the aged and ≥ 6 h anesthesia time subgroup. CONCLUSIONS: High initial dPs ≥ 10 cmH2O at GA induction predicted longer POS than those of approximately 7 cmH2O. High initial dPs were, however, a secondary factor for prolongation of postoperative hypoxemia in old age and prolonged surgery.

Patient-ventilator asynchrony, impact on clinical outcomes and effectiveness of interventions: a systematic review and meta-analysis.

BACKGROUND: Patient-ventilator asynchrony (PVA) is a common problem in patients undergoing invasive mechanical ventilation (MV) in the intensive care unit (ICU), and may accelerate lung injury and diaphragm mis-contraction. The impact of PVA on clinical outcomes has not been systematically evaluated. Effective interventions (except for closed-loop ventilation) for reducing PVA are not well established. METHODS: We performed a systematic review and meta-analysis to investigate the impact of PVA on clinical outcomes in patients undergoing MV (Part A) and the effectiveness of interventions for patients undergoing MV except for closed-loop ventilation (Part B). We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, ClinicalTrials.gov, and WHO-ICTRP until August 2020. In Part A, we defined asynchrony index (AI) ≥ 10 or ineffective triggering index (ITI) ≥ 10 as high PVA. We compared patients having high PVA with those having low PVA. RESULTS: Eight studies in Part A and eight trials in Part B fulfilled the eligibility criteria. In Part A, five studies were related to the AI and three studies were related to the ITI. High PVA may be associated with longer duration of mechanical ventilation (mean difference, 5.16 days; 95% confidence interval [CI], 2.38 to 7.94; n = 8; certainty of evidence [CoE], low), higher ICU mortality (odds ratio [OR], 2.73; 95% CI 1.76 to 4.24; n = 6; CoE, low), and higher hospital mortality (OR, 1.94; 95% CI 1.14 to 3.30; n = 5; CoE, low). In Part B, interventions involving MV mode, tidal volume, and pressure-support level were associated with reduced PVA. Sedation protocol, sedation depth, and sedation with dexmedetomidine rather than propofol were also associated with reduced PVA. CONCLUSIONS: PVA may be associated with longer MV duration, higher ICU mortality, and higher hospital mortality. Physicians may consider monitoring PVA and adjusting ventilator settings and sedatives to reduce PVA. Further studies with adjustment for confounding factors are warranted to determine the impact of PVA on clinical outcomes. Trial registration protocols.io (URL: https://www.protocols.io/view/the-impact-of-patient-ventilator-asynchrony-in-adu-bsqtndwn , 08/27/2020).

Prevalence of rapid response systems in small hospitals: A questionnaire survey.

ABSTRACT: The rapid response system (RRS) was introduced for early stage intervention in patients with deteriorating clinical conditions. Responses to unexpected in-hospital patient emergencies varied among hospitals. This study was conducted to understand the prevalence of RRS in smaller hospitals and to identify the need for improvements in the responses to in-hospital emergencies.A questionnaire survey of 971 acute-care hospitals in western Japan was conducted from May to June 2019 on types of in-hospital emergency response for patients in cardiac arrest (e.g., medical emergency teams [METs]), before obvious deterioration (e.g., rapid response teams [RRTs]), and areas for improvement.We received 149 responses, including those from 56 smaller hospitals (≤200 beds), which provided fewer responses than other hospitals. Response systems for cardiac arrest were used for at least a limited number of hours in 129 hospitals (87%). The absence of RRS was significantly more frequent in smaller hospitals than in larger hospitals (13/56, 23% vs 1/60, 2%; P < .01). METs and RRTs operated in 17 (11%) and 15 (10%) hospitals, respectively, and the operation rate for RRTs was significantly lower in smaller hospitals than in larger hospitals (1/56, 2% vs 12/60, 20%; P < .01). Respondents identified the need for education and more medical staff and supervisors; data collection or involvement of the medical safety management sector was ranked low.The prevalence of RRS or predetermined responses before obvious patient deterioration was ≤10% in small hospitals. Specific education and appointment of supervisors could support RRS in small hospitals.

Pediatric Fulminant Myocarditis in Japan: A Retrospective Nationwide Database Study of Hospital Volume, Management Practices, and Mortality.

OBJECTIVES: Pediatric fulminant myocarditis is a subset of pediatric acute myocarditis associated with critical illness. We aimed to compare mortality and other outcomes such as length of hospital stay between pediatric fulminant myocarditis and nonfulminant myocarditis. For the subgroup of patients with fulminant myocarditis, we also aimed to describe the current management practices and evaluate the impact of clinically relevant factors, including hospital case volume, on mortality. DESIGN: Retrospective observational study using the Diagnosis Procedure Combination database from April 2012 to March 2018. SETTING: Over 1,000 acute care hospitals in Japan. PATIENTS: Patients with acute myocarditis less than 18 years old, including patients with fulminant myocarditis (i.e., those who received at least one of the following by day 7 of hospitalization: inotropes/vasopressors, mechanical circulatory support, or cardiopulmonary resuscitation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Multivariable logistic regression analysis was conducted to investigate the association between clinically relevant factors and in-hospital mortality of patients with fulminant myocarditis. Furthermore, post hoc propensity score analyses (propensity score-adjusted, propensity score-matched, and inverse probability of treatment-weighted analyses) were performed to confirm the effect of hospital case volume on in-hospital mortality. In total, 866 pediatric patients with acute myocarditis were included, and 382 (44.1%) were categorized as fulminant myocarditis. In-hospital mortality for those with fulminant myocarditis was 24.1%. fulminant myocarditis was associated with 41.3-fold greater odds of mortality than nonfulminant myocarditis (95% CI, 14.7-115.9; p < 0.001). In the subgroup of patients with fulminant myocarditis, a higher in-hospital mortality was significantly associated with younger age (≤ 5 yr; odds ratio, 3.41; 95% CI, 1.75-6.64) and the need for either mechanical ventilation (odds ratio, 2.39; 95% CI, 1.03-5.57), cardiopulmonary resuscitation (odds ratio, 10.63; 95% CI, 5.52-20.49), or renal replacement therapy (odds ratio, 2.53; 95% CI, 1.09-5.87) by day 7. A lower in-hospital mortality rate was significantly associated with treatment at hospitals in the highest pediatric fulminant myocarditis case volume tertile (≥ 6 cases in 6 yr; odds ratio, 0.30; 95% CI, 0.13-0.68) compared with treatment at hospitals in the lowest tertile (1-2 cases in 6 yr). Post hoc propensity score analyses consistently supported the primary results. CONCLUSIONS: In-hospital mortality of pediatric fulminant myocarditis in Japan remains high. Treatment at hospitals in the highest pediatric fulminant myocarditis case volume tertile (≥ 6 cases in 6 yr) was associated with a 70% relative reduction in odds of in-hospital mortality compared with treatment at hospitals in the lowest tertile (1-2 cases in 6 yr). The reasons for such differences need further study.

Hypothermia, Poorly Recognized by clinicians, is associated with Higher Mortality Among Critically Ill Patients with infections: A Retrospective Observational Study.

We investigated the relationship between the presence of hypothermia in infection and mortality in 233 infectious critically ill patients. The adjusted hazard ratio for death at 28 days in the low body temperature group was 3.30 compared with the high body temperature group. The proportion of appropriate antimicrobial therapy significantly decreased with decreasing body temperature. The proportion of medical records that documented body temperature abnormality in the low body temperature group (33%) was significantly lower than that in the high body temperature group (69%). Delayed antimicrobial therapy in patients with hypothermia, which may be due to poor recognition by physicians, could result in mortality.

Pharmacological and Genetic Inhibition of Translocator Protein 18 kDa Ameliorated Neuroinflammation in Murine Endotoxemia Model.

ABSTRACT: Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction associated with sepsis. The development of an effective strategy for early diagnosis and therapeutic intervention is essential for the prevention of poor prognosis of SAE. Translocator protein 18 kDa (TSPO) is a mitochondrial protein implicated in steroidogenesis and inflammatory responses. Despite accumulating evidence that implicates TSPO in the neuroinflammatory response of the central nervous system, the possible role of TSPO in SAE remains unclear. The aim of this study is to address a role of TSPO in neuroinflammation using mice 24 h after systemic injection of LPS, which consistently demonstrated microglial activation and behavioral inhibition. Quantitative polymerase chain reaction analysis revealed that hippocampal TSPO expression was induced following the systemic LPS injection, associated with an increase in pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-1ß. Interestingly, pretreatment with the TSPO antagonist, ONO-2952, or germ-line deletion of the TSPO gene exhibited an anti-inflammatory effect with significant suppression of LPS-induced production of those cytokines. These effects demonstrated by the ONO-2952 or TSPO knockout were associated with significant recovery from behavioral inhibition, as shown by improved locomotor activity in the open field analysis. Histological analysis revealed that ONO-2952 pretreatment suppressed the LPS-induced activation of TSPO-expressing microglia in the hippocampus of mice. Collectively, these results suggest that TSPO plays a critical role in the SAE mouse model. Based on this finding, monitoring TSPO activity, as well as the progress of endotoxemia and its sequelae in the animal model, would deepen our understanding of the underlying molecular mechanism of SAE.

Microglial translocator protein and stressor-related disorder.

Despite the prevalence of neuroinflammation in psychiatric disorders, molecular mechanism underlying it remains elusive. Translocator protein 18 kDa (TSPO), also known as peripheral benzodiazepine receptor, is a mitochondrial protein implicated in the synthesis of steroids in a variety of tissues. Multiple reports have shown increased expression of TSPO in the activated microglia in the CNS. Radioactive probes targeting TSPO have been developed and used for imaging assessment in neurological and psychiatric disorders to examine neuroinflammation. Recent studies revealed that the wide range of stressors ranging from psychological to physical insults induced TSPO in human, suggesting that this protein could be an important tool to explore the contribution of microglia in stressor-related disorders. In this review, we first overview the microglial activation with TSPO in a wide range of stressors in human and animal models to discuss prevalent roles of TSPO in response of CNS to stressors. With recent update of the signaling pathway revealing link connecting TSPO with neuroinflammatory effectors such as reactive oxygen species, we discuss TSPO as a therapeutic targeting tool for suppression of adverse effect of stressors on long-lasting changes in animal behaviors and activities. Targeting TSPO which mediates neuroinflammation under the stress might pave the way to develop therapeutic intervention and prophylaxis of stressor-related disorder.

Prognosis of pathogen-proven acute respiratory distress syndrome diagnosed from a protocol that includes bronchoalveolar lavage: a retrospective observational study.

BACKGROUND: To treat patients with acute respiratory distress syndrome (ARDS), it is important to diagnose specific lung diseases and identify common risk factors. Our facility focuses on using bronchoalveolar lavage (BAL) to identify precise risk factors and determine the causative pathogen of ARDS within 24 h of intensive care unit (ICU) admission. This study evaluated the prognoses of pathogen-proven ARDS patients who were diagnosed or identified with risk factors using a diagnostic protocol, which included BAL, compared with the prognoses of pathogen-unproven ARDS patients. METHODS: This retrospective observational study was conducted in the ICU at a tertiary hospital from October 2015 to January 2019. We enrolled patients with respiratory distress who were on mechanical ventilation for more than 24 h in the ICU and who were subjected to our diagnostic protocol. We compared the disease characteristics and mortality rates between pathogen-proven and pathogen-unproven ARDS patients. RESULTS: Seventy ARDS patients were included, of whom, 50 (71%) had pathogen-proven ARDS as per our protocol. Mortality rates in both the ICU and the hospital were significantly lower among pathogen-proven ARDS patients than among pathogen-unproven ARDS patients (10% vs. 50%, p = 0.0006; 18% vs. 55%, p = 0.0038, respectively). Pathogen-proven ARDS patients were independently associated with hospital survival (adjusted hazard ratio, 0.238; 95% confidence interval, 0.096-0.587; p = 0.0021). CONCLUSIONS: Our diagnostic protocol, which included early initiation of BAL, enabled diagnosing pathogen-proven ARDS in 71% of ARDS patients. These patients were significantly associated with higher hospital survival rates. The diagnostic accuracy of our diagnostic protocol, which includes BAL, remains unclear.

Factors related to memory absence and delusional memories in patients in intensive care units managed with light sedation.

OBJECTIVES: Currently, light sedation is typically given to patients in intensive care units and studies have not extensively examined the factors related to absences or abnormalities of their memories. We, therefore, analysed the factors related to the absence/abnormalities of patients' memories in intensive care units. RESEARCH METHODOLOGY: A secondary analysis of previously collected survey data examining patients' experiences in an intensive care unit was undertaken (n = 405; women = 38%; median age = 70 years). To observe absent or distorted memories, patients were interviewed after leaving the intensive care unit. We analysed key factors through content analysis of the interviews and field notes. SETTING: The intensive care unit of a university hospital. MAIN OUTCOME MEASURE: Patients' absent or distorted memories after leaving the intensive care unit. RESULTS: Half the patients reported an absence of memories. This was associated with old age and with longer duration of mechanical ventilation. Absent or fragmentary memories were not distressing. Fragmentary and fearful intensive care unit memories were associated with being older. Delusional memories, some of which reflected actual events, were present in 3% of patients. CONCLUSION: Absence of memories were not distressing, delusional memories occurred less and these memories could comprise of an event in ICU that is difficult for patients to understand.

High serum potassium level is associated with successful electrical cardioversion for new-onset atrial fibrillation in the intensive care unit: A retrospective observational study.

Electrical cardioversion (ECV) is a potentially life-saving treatment for haemodynamically unstable new-onset atrial fibrillation (AF); however, its efficacy is unsatisfactory. We aimed to elucidate the factors associated with successful ECV and prognosis in patients with AF. This retrospective observational study was conducted in two mixed intensive care units (ICUs) in a university hospital. Patients with new-onset AF who received ECV in the ICU were enrolled. We defined an ECV session as consecutive shocks within 15 minutes. The success of ECV was evaluated five minutes after the session. We analysed the factors associated with successful ECV and ICU mortality. Eighty-five AF patients who received ECV were included. ECV was successful in 41 (48%) patients, and 11 patients (13%) maintained sinus rhythm until ICU discharge. A serum potassium level ≥3.8 mol/L was independently associated with successful ECV in multivariate analysis (odds ratio (OR), 3.13; 95% confidence interval (CI), 1.07-9.11; p = 0.04). Maintenance of sinus rhythm until ICU discharge was significantly associated with ICU survival (OR 9.35; 95% CI 1.02-85.78, p = 0.048). ECV was successful in 48% of patients with new-onset AF developed in the ICU. A serum potassium level ≥3.8 mol/L was independently associated with successful ECV, and sinus rhythm maintained until ICU discharge was independently associated with ICU survival. These results suggested that maintaining a high serum potassium level may be important when considering the effectiveness of ECV for AF in the ICU.

Retrospective immunohistological study of autopsied lungs in patients with acute exacerbation of interstitial pneumonia managed with extracorporeal membrane oxygenation.

BACKGROUND: Acute exacerbation of interstitial pneumonia (AE-IP) is a life-threatening pulmonary condition that involves various pathogeneses. In patients with AE-IP who need mechanical ventilation with high driving pressure and oxygen concentration, veno-venous extracorporeal membrane oxygenation (V-V ECMO) may diminish alveolar epithelial damage by decreasing ventilator settings. The pathophysiological benefit of this therapeutic option is not well investigated. METHODS: We retrospectively collected 15 autopsied patients with AE-IP who were treated with mechanical ventilation in the intensive care unit (ICU) at Hiroshima University Hospital (Hiroshima, Japan) between 2010 and 2016. The patients were grouped by whether they were managed with mechanical ventilation only (the ventilator group, n=6) or with mechanical ventilation and V-V ECMO (the ECMO group, n=9). RESULTS: The median age of the ventilator and ECMO group patients were similar (65 and 64 years, respectively). The severity score APACHE II in the ECMO group (35.0) is significantly higher than that of ventilator group (14.5) (P=0.006). Ventilator days were significantly shorter in the ventilator group (17.5 days) than in the ECMO group (30.0 days) (P=0.04). Compared with the ECMO group, the ventilator group had a stronger Masson-trichrome stain grade (4 vs. 6, P=0.04) and higher immunoreactivity grades for Krebs von den Lungen-6 (4 vs. 6, P=0.04) and IL-8 (3 vs. 6, P=0.02). Between the ventilator and ECMO groups, the immunoreactivity grades of angiopoietin 2 (4 vs. 1, P=0.08) and receptor for advanced glycation end products (2 vs. 1, P=0.52) did not differ. CONCLUSIONS: The lungs of mechanically ventilated AE-IP patients treated with V-V ECMO had decreased fibrosis, endothelial injury, and inflammation. This finding suggests the lung-protective efficacy of adjunctive V-V ECMO therapy.

Effects of acute ethanol intoxication in an ovine peritonitis model.

BACKGROUND: Acute ethanol intoxication has been shown to have contrasting effects on outcomes in sepsis. The aim of this study was to explore the effects of acute ethanol intoxication on hemodynamics, renal function, brain perfusion and lactate/pyruvate in an ovine sepsis model. METHODS: Anesthetized, mechanically ventilated female sheep were randomized to an ethanol group (n = 7), which received 1 g/kg ethanol diluted in intravenous (i.v.) saline infusion or a control group (n = 7), which received the same volume of i.v. saline. Both groups received the treatment for a period of 2 h prior to induction of sepsis by intraperitoneal injection of feces. Other treatment included fluid resuscitation but no vasopressors or antibiotics. Global hemodynamics, renal blood flow, brain cortex laser Doppler flowmetry and microdialysis analyses were recorded hourly. RESULTS: In the ethanol group, blood ethanol concentrations were 137 ± 29 mg/dL at the time of feces injection and decreased to become undetectable by 12 h. Arterial hypotension occurred earlier in the ethanol than in the control group (8 [7-12] vs. 14 [11-20] hours, p = 0.03). Lactate levels increased to > 2 mmol/L earlier in the ethanol group. Renal dysfunction (9 [6-13] vs. 13 [12-15] hours, p = 0.05) and oliguria (urine output < 0.5 mL/kg/h; 10 [7-12] vs. 13 [12, 13] hours, p = 0.01) developed earlier in the ethanol than in the control group. Brain blood flow and lactate/pyruvate were unaffected. There was no significant difference in survival time. CONCLUSIONS: Acute ethanol intoxication in this model of peritonitis resulted in earlier development of shock and renal dysfunction but did not alter brain perfusion and metabolism or short-term survival.

Rapid-onset plasma leakage of extracorporeal oxygenation membranes possibly due to hyperbilirubinemia.

Extracorporeal membrane oxygenation (ECMO) is an emerging tool for supporting cardiopulmonary function in patients with cardiorespiratory failure or arrest. The oxygenator of the ECMO circuit requires effective oxygenation and removal of carbon dioxide from the blood. Major problems that can occur with the oxygenator include plasma leakage, one of the late-onset serious complications necessitating device replacement. However, the rapid onset of plasma leakage is rare. We present a 1-year-old boy with acute respiratory failure due to Pneumocystis and Aspergillus pneumonia. He presented with tachypnea, tachycardia, and hypoxemia despite the ventilatory support, and was therefore placed on venoarterial ECMO with a drainage catheter from the right internal jugular vein (12 Fr) and a return catheter to the right internal carotid artery (10 Fr). Extracorporeal circulation was initiated at a blood flow of 1 L/min (145 mL/kg/min) and a sweep gas flow of 1 L/min with FiO2 of 0.7. Although he was successfully weaned from the venoarterial ECMO on day 15 with an improvement of cardiopulmonary function, he was later placed on venoarterial ECMO again because of the progression of pulmonary hypertension. Laboratory tests showed increased concentrations of hepatic enzymes and hyperbilirubinemia (total bilirubin 31.6 mg/dL). Six hours after starting ECMO circulation, plasma leakage from the oxygenator occurred. Although we replaced the oxygenator with a new one, the replacement showed plasma leakage after 6 h. Disassembly of the oxygenator revealed congestion from bilirubin in the membrane fibers. We described a case of repeated, rapid-onset plasma leakage after implementation of ECMO. Hyperbilirubinemia was likely associated with the plasma leakage of this patient.