Venous-arterial Extracorporeal Membrane Oxygenation Research Articles

Clinical observation of venous-arterial extracorporeal membrane oxygenation in the treatment of refractory septic shock in children

Objective To investigate the efficacy of venous-arterial extracorporeal membrane oxygenation (VA-ECMO) in the treatment of refractory septic shock in children. Methods From January 2016 to December 2018, the clinical data of children with refractory septic shock (RSS) treated by VA-ECMO in Department of Critical Medicine Affiliated Children's Hospital of Shanghai Jiao Tong University were retrospectively analyzed. The patients with refractory septic shock (RSS) treated by VA-ECMO were compared with those with non-refractory septic shock (NRSS). Results There were 8 cases in the RSS-ECMO group and 6 cases in the NRSS-ECMO group. The sex, age, PRISM score, complication showed no significant difference in the two groups. The median time of ECMO in the RSS-ECMO group was 182 (141, 216) h , and 5 patients were survived and were discharged from the hospital. The blood lactic acid and vasoactive drug index in the RSS-ECMO group was significantly higher than that in the NRSS-ECMO group (P 0.05). After ECMO establishment, the mean invasive arterial pressure increased significantly at 6 h, and lactic acid decreased significantly at 12 h after ECMO support. SCVO2 returned to normal at 24-h ECMO therapy. Conclusions The success rate of VA-ECMO treatment in children with refractory septic shock complicated with MODS is similar to that of children with non-refractory septic shock. The relationship between ECMO and hemodynamic indexes in sepsis should be further explored. Key words: Venoarterial extracorporeal membrane oxygenation (VA-ECMO); Continuous renal replacement therapy (CRRT); Sepsis; Refractory septic shock; Mortality; Child

IP117. Leg Complication Predictors in Peripherally Cannulated Venous-Arterial Extracorporeal Membrane Oxygenation Patients

IP117. Leg Complication Predictors in Peripherally Cannulated Venous-Arterial Extracorporeal Membrane Oxygenation Patients

Left Ventricle Decompression Strategies in Pediatric Peripheral Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is widely used in patients with potentially reversible acute cardiac and/or pulmonary failure who are unresponsive to conventional treatment. Patients with profound left ventricular (LV) dysfunction under venous-arterial (V-A) ECMO may experience LV distention, pulmonary edema, and thrombus formation. It is critical to unload the left ventricle to prevent such complications. The aim of this study was to identify the risks, timing and methods of LV decompression in pediatric peripheral ECMO. Between August 2006 and November 2017, 51 patients received peripheral ECMO support in our pediatric intensive care unit. All of them were less than 18 years of age and non-cardiotomy surgery-related. We retrospectively reviewed the patients' clinical presentations, decompression methods and outcomes. The overall success rate of ECMO removal was 76.5% (39/51), and the survival rate after discharge was 62.7% (32/51). The myocarditis group had the most favorable outcomes among the ECMO patients (100% survival). LV decompression was needed in 12 patients who had profound LV dysfunction under V-A ECMO. Five patients received medical treatment successfully, and the other 7 patients underwent intra-aortic balloon pump (IABP) procedures. In the IABP group, 1 patient still needed further pigtail-decompression. All of our decompression patients survived with good neurological outcomes (Glasgow Outcome Scale 5). The patients with profound LV dysfunction under peripheral VA ECMO were at risk of thromboembolic events and LV decompress was needed. If medical decompression fails, IABP is a feasible approach for LV decompression in pediatric peripheral ECMO.

Extra corporeal membrane oxygenation in the critical trauma patient

The purpose of this review is to describe recent evidence regarding the use of extracorporeal membrane oxygenation (ECMO) as salvage therapy for severe cardiac or respiratory failure in patients with trauma. The characteristics of this cohort of patients, including the risk of bleeding and the need for systemic anticoagulation, are generally considered as relative contraindications to ECMO treatment. However, recent evidence suggests that the use of ECMO should be taken in consideration even in this group of patients. The recent findings suggest that venous-venous ECMO can be feasible in the treatment of refractory respiratory failure and severe acute respiratory distress syndrome trauma-related. The improvement of ECMO techniques including the introduction of centrifugal pumps and heparin-coated circuits are progressively reducing the amount of heparin required; moreover, the application of heparin-free ECMO showed good outcomes and minimal complications. Venous-arterial ECMO has emerged as a salvage intervention in patients with cardiogenic shock and after cardiac arrest. Venous-arterial ECMO provides circulatory support allowing time for other treatments to promote recovery in presence of acute cardiopulmonary failure. Only poor-quality evidence is available, for venous-arterial ECMO in trauma patients. ECMO can be considered as a safe rescue therapy even in trauma patients, including neurological injury, chest trauma as well as burns. However, evidence is still poor; further studies are warranted focusing on trauma patients undergoing ECMO, to better clarify the effect on survival, the type and dose of anticoagulation to use, as well as the utility of dedicated multidisciplinary trauma-ECMO units.

Association between left ventricular outflow tract opening and successful resuscitation after cardiac arrest

BackgroundSurvival after cardiac arrest depends on adequate cardiopulmonary resuscitation (CPR). Manual or mechanical external chest compression may be ineffective to restore circulation: structures subjected to external chest compression may differ in forces transfer to intrathoracic structures due to anatomic characteristics and physiological changes.This clinical study aims to assess the association of trans-oesophageal findings during CPR and successful resuscitation. MethodsRetrospective cohort study. Trans-oesophageal assessment of right ventricular fractional area change, right ventricular outflow tract fractional shortening, left ventricular volumes, ejection fraction, and aortic diameters were performed in refractory out-of-hospital cardiac arrest patients admitted to emergency department for extracorporeal CPR. Results19 patients were analyzed. 15 of 19 patients (79%) received venous-arterial extracorporeal membrane oxygenation support. Resuscitation was successful with return of spontaneous circulation or electromechanical activity in 7 patients (group-SUXX) and failed in 12 patients (group-FAIL). 6 patients (32%) were alive at 24 h from the cardiac arrest, one patient (5%) survived to hospital discharge. Left ventricular outflow tract (LVOT) was open during CPR in all patients in group-SUXX and in 1 patient in group-FAIL (p 0.0002). None of the patients with closed LVOT had successful resuscitation. Patients in group-SUXX had a higher ejection fraction (p 0.03), ascending aortic diameter (p 0.04), and survival rate than those in group-FAIL (p 0.015). In a multiple variable Cox’s proportional model LVOT opening was the only variable associated with successful resuscitation. ConclusionsTrans-oesophageal echocardiography can be useful in the emergency setting of cardiopulmonary arrest for discriminating between successful and failing resuscitation.

An audit of mortality by using ECMO specific scores and APACHE II scoring system in patients receiving extracorporeal membrane oxygenation in a tertiary intensive care unit in Hong Kong

Outcomes of patients receiving extracorporeal membrane oxygenation (ECMO) therapies risk-adjusted by ECMO specific scores have rarely been reported. Our primary aim was to determine the risk adjusted outcome of these patients by the use of Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP), Survival After Veno-Arterial-ECMO (SAVE) and APACHE II scores. The differences in predicted mortality between these scoring systems were analyzed. This is a single-center retrospective study reviewing 62 patients who received venous-venous ECMO (VV-ECMO) and venous-arterial ECMO (VA-ECMO) between 2009 and 2017 in a tertiary ICU. Demographic, clinical, laboratory, imaging data were analyzed. Primary outcome measures were the crude mortality and standardized mortality ratio (SMR), expressed as observed mortality divided by expected mortality predicted from RESP, SAVE and APACHE II scores, respectively. We also examined the difference in predicted mortality derived from RESP, SAVE, and APACHE II by using Bland Altman plots. Twenty and Forty-two patients received VV-ECMO (20 runs) and VA-ECMO (43 runs) respectively. For VV-ECMO, the mean RESP was 0.6 [standard deviation (SD) 4.86] with RESP-SMR of 1.16 [95% confidence interval (95% CI) =0.44-1.88]. For VA-ECMO, the mean SAVE score was -7.8 (SD 5.6), with SAVE-SMR of 0.69 (95% CI =0.39-0.98). In the Bland Altman plot for VA-ECMO, mean difference in predicted mortality between SAVE and APACHE II was 17.6% (95% CI: 7.6% to 27.6%, P<0.0001), with 95% limit of agreement of -30.2% to 65.5% and beta coefficient of -1.04. APACHE II predicted mortality for VA-ECMO was lower than that for SAVE until it crossed SAVE prediction at about 80% mortality. After this point, it becomes progressively higher than that for SAVE. The mortality outcome of our patients on VV-ECMO and VA-ECMO compares favorably with predicted mortality based on RESP and SAVE, respectively. In our cohort of patients receiving VA-ECMO, APACHE II tends to underestimate mortality in lower risk patients, and overestimate the mortality in patients at high risk of death.

The influence of advanced age on venous-arterial extracorporeal membrane oxygenation outcomes.

Ethical and health care economic concerns surround the use of venous-arterial extracorporeal membrane oxygenation (VA-ECMO) in elderly patients. Patients requiring VA-ECMO are often in critical condition and the decision to cannulate is time-sensitive. We investigated the relationship between age and VA-ECMO outcomes to better inform this decision. This is a retrospective study of 355 patients placed on VA-ECMO between March 2007 and August 2016 at our institution. Using piecewise modelling, age became associated with in-hospital mortality after 63 years. Based on further analysis with the χ2 statistic maximization, patients were divided into 2 age groups: ≤72 years old [Group Y (Young), n = 310] and >72 years old [Group O (Old), n = 45]. Multivariable logistic regression was performed to identify preoperative predictors of in-hospital mortality. Patients over the age of 72 had a significantly higher prevalence of comorbidities, including coronary disease, previous strokes and chronic kidney disease. Weaning from ECMO was achieved in 76% of Group Y and 47% of Group O (P < 0.001). In-hospital mortality was 52% among Group Y and 69% among Group O (P = 0.037). Multivariable logistic regression using preoperative risk factors identified coronary artery disease, acute decompensated heart failure and an age >72 years as independent predictors of mortality (age >72 years: odds ratio 2.71, 95% confidence interval 1.22-6.00; P = 0.01). VA-ECMO in-hospital mortality is considerable across all age groups. However, age only becomes associated with mortality after 63 years and rises dramatically after 72 years. This study provides useful insight into these time-sensitive decisions for the development of possible practice guidelines.

Prevalence, risk factors, and prognosis of ischemic hepatitis during venous-arterial extracorporeal membrane oxygenation

Objective Ischemic hepatitis(IH) is acute ischemic damage in liver caused by hypoxemia and hypoperfusion. However, the prevalence, risk factors and prognosis of IH during venous-arterial extracorporeal membrane oxygenation(ECMO) were rarely reported. Methods A total of 82 adult patients (≥18 years) with cardiac diseases were enrolled for venous-arterial(VA) ECMO in this study. These patients afflicted with IH and non-IH (NIH) were assigned into two groups. Results A total of 20 patients (24.4%) were afflicted with IH within 24 h during ECMO. In these patients, AST decreased over time, but the levels of total bilirubin(TBIL) increased gradually. The survival rate of IH group was significantly lower than that of NIH group (15% vs 50%, P=0.006). The incidence of acute renal failure was higher in IH group(70.0% vs 41.9%, P=0.029). More albumin was required in IH group (P=0.002). In the multivariable regression model, medical heart failure[(odds ratio, OR)=149.71, 95%CI 6.22-3 602.58, P=0.002], peak lactate (OR=1.41, 95%CI 1.14-1.76, P=0.002) and peak TBIL (OR=1.02, 95%CI 1.01-1.04, P=0.010) within the first 24 h during ECMO were risk factors for IH. The survival rate of IH group was significantly lower than that in NIH group (50% vs 15%, P=0.006). Conclusions Patients with medical heart failure, high levels of peak lactate and peak TBIL during ECMO have higher risk to develop IH. Key words: Ischemic hepatitis; Extracorporeal membrane oxygenation; Risk factors

Percutaneous Mechanical Circulatory Support Devices in Cardiogenic Shock

Despite a high rate of early revascularization and use of intra-aortic balloon pump counterpulsation therapy, the prognosis of patients with cardiogenic shock has remained poor. In the hopes of improving outcomes, clinicians are increasingly turning to percutaneous left and right mechanical circulatory support devices. Until recently, the evidence base for these devices had consisted only of observational data, meta-analyses, and small feasibility trials. In this article, we describe the contemporary outcomes of patients with cardiogenic shock, the hemodynamics of cardiogenic shock, and hemodynamic effects of percutaneous mechanical circulatory support devices. We then use this discussion to provide clinicians with a useful framework for understanding when selecting between or while managing patients with a percutaneous mechanical circulatory support devices. We critically review the recently published data for and against the use of commercially available devices-the intra-aortic balloon pump counterpulsation, the Impella system, the TandemHeart, and venous-arterial extracorporeal membrane oxygenation-and highlight gaps in our understanding. Given such gaps, a consensus multidisciplinary approach that combines expertise from interventional cardiologists, heart failure specialists, cardiac surgeons, and cardiac anesthesiologists may help pair the right patient with the right device at the right time.

Post Cardiotomy via ECMO Current Results for Venous Arterial ECMO Post Cardiac Surgery –- Impact on Mediastinal Haemostasis and Transfusion Requirements

Post Cardiotomy via ECMO Current Results for Venous Arterial ECMO Post Cardiac Surgery –- Impact on Mediastinal Haemostasis and Transfusion Requirements

Peripheral Vascular Complications Are Associated with Increased Mortality in Patients on Femoral Venous Arterial ECMO

147 patients from January 2008 to August 2015 underwent VA ECMO therapy at a single institution. The mean age of the patients was 49 ± 14 years (16 to 85 years) and 64% (n = 94) were male. The primary indications for VA-ECMO were primary graft failure post heart transplant (29%), cardiac arrest (22%) and post cardiotomy shock (19%). Despite 93% of patients having a backflow cannula, 25% still developed distal limb ischaemia leading to compartment syndrome in 10% and amputation in 4%. Age, diabetes and dialysis were strong predictors of distal limb ischaemia. Patients with pre-existing peripheral vascular disease were significantly at risk of compartment syndrome (p = 0.014) and amputation (p = 0.007). 30-day mortality was 50% in patients with compartment syndrome. Peripheral cannulation for VA ECMO can lead to ischaemic complications in significant numbers of patients in cardiogenic shock. Once these complications develop, patient outcomes are grim. Patients requiring femoral ECMO must be carefully assessed for vascular complications post insertion. Early intervention is vital with consideration given for alternate sites of cannulation.

Pediatric Cardiac Arrest Due to Trauma

Survival from pediatric cardiac arrest due to trauma has been reported to be 0.0%–8.8%. Some argue that resuscitation efforts in the case of trauma-related cardiac arrests are futile. We describe a successful outcome in the case of a child who suffered cardiac arrest caused by external traumatic airway obstruction. Our case illustrates how to deal with pediatric traumatic cardiac arrests in an out-of-hospital environment. It also illustrates how good clinical treatment in these situations may be supported by correct treatment after hospital admission when it is impossible to ventilate the patient to provide sufficient oxygen delivery to vital organs. This case relates to a lifeless child of 3–5 years, blue, and trapped by an electrically operated garage door. The first ambulance arrived to find several men trying to bend the frame and the door apart in order to extricate the child, who was hanging in the air with head and neck squeezed between the horizontally-moving garage door and the vertical door frame. One paramedic found a car jack and used it to push the door and the frame apart, allowing the lifeless child to be extricated. Basic life support was then initiated. Intubation was performed by the anesthesiologist without drugs. With FiO2 1.0 the first documented SaO2 was <50%. Restoration of Spontaneous Circulation was achieved after thirty minutes, and she was transported to the hospital. After a few hours she was put on venous-arterial ECMO for 5.5 days and discharged home after two months. Outpatient examinations during the rest of 2013 were positive, and the child found not to be suffering from any injuries, either physical or mental. The last follow-up in October 2014 demonstrated she had made a 100% recovery and she started school in August 2014.

Plasma Free Hemoglobin Is a Predictor of Acute Renal Failure During Adult Venous-Arterial Extracorporeal Membrane Oxygenation Support.

Hemolysis is a common and severe complication during extracorporeal membrane oxygenation (ECMO). Increased plasma free hemoglobin (PFHb) is related to renal injury. The aim of this study was to investigate whether increased PFHb during adult venous-arterial ECMO was associated with acute renal failure (ARF). A retrospective, observational, single-center study. Fuwai Hospital in Beijing, China. The study comprised 84 venous-arterial ECMO patients. None. A total of 84 consecutive adult patients (≥18 years) with cardiac diseases requiring venous-arterial ECMO support were studied retrospectively. Demographics of patients, clinical and ECMO characteristics, and PFHb level were collected within the first 3 days after ECMO. ARF was defined as a≥300% rise in serum creatinine from baseline or application of dialysis. Repeated measurement analysis of variance revealed that the main effect for the non-ARF group and ARF group in PFHb (p = 0.002) was significant. A significant main effect for time points (p<0.001) and time×group interaction (p = 0.014) in PFHb was obtained. In a multiple logistic regression model, peak PFHb during ECMO (odds ratio 1.052, 95% confidence interval 1.016-1.089, p = 0.005) was a risk factor for ARF during ECMO and patients who underwent heart transplantation (odds ratio 0.240, 95% confidence interval 0.060-0.964, p = 0.044) experienced less ARF. There was a linear correlation between peak serum creatinine and peak PFHb (Spearman's r = 0.223, p = 0.042). Increased PFHb is a predictor of ARF among adult patients on venous-arterial ECMO support.

Extracorporeal Membrane Oxygenation as a Procedural Rescue Strategy for Transcatheter Aortic Valve Replacement Cardiac Complications.

Cardiovascular complications during or after transcatheter aortic valve replacement (TAVR) are associated with extremely high mortality, but extracorporeal membrane oxygenation (ECMO) can be used as procedural rescue option to improve outcomes when patients experience respiratory or cardiac arrest. From 2012 to 2014, 230 patients underwent TAVR and 10 patients (4.3%) required emergent venous-arterial ECMO support. Mean age was 83 years, median Society of Thoracic Surgeons (STS) score was 15, and mean aortic gradient was 45 mm Hg. Median left ventricular ejection fraction was 35%. Access for most ECMOs was femoral; two patients required central arterial and femoral venous access. Extracorporeal membrane oxygenation was initiated in response to hemodynamic collapse due to perforation of left ventricle (n = 2), aortic root rupture (n = 1), moderate-to-severe aortic insufficiency (n = 1), left main impingement (n = 1), valve embolization (n = 1), severe hypotension and cardiac arrest after prolonged rapid pacing sequence (n = 1), ventricular fibrillation (n = 2), and ventricular tachycardia (n = 1). Median time of ECMO support was 87 minutes. There were three hospital deaths. Post-TAVR mean aortic gradient was 8 mm Hg and median hospital stay was 19 days. Additional procedures included valve-in-valve placement (n = 1), percutaneous coronary intervention (n = 1), surgical LV repair (n = 2), surgical valve replacement (n = 1), aortic root rupture repair, and coronary bypass grafting (n = 1). Extracorporeal membrane oxygenation is rescue therapy for hemodynamic instable patients who develop TAVR-related cardiac complications.

Predictors of Acute Renal Failure During Extracorporeal Membrane Oxygenation in Pediatric Patients After Cardiac Surgery.

Acute renal failure (ARF) is associated with increased mortality in pediatric extracorporeal membrane oxygenation (ECMO). The aim of this study was to identify predictors of ARF during ECMO in pediatric patients after cardiac surgery. A retrospective study analyzed 42 children (≤15 years) after cardiac surgery requiring venous-arterial ECMO between December 2008 and December 2014 at Fuwai Hospital. ARF was defined as ≥300% rise in serum creatinine (SCr) concentration from baseline or application of dialysis. Multivariate logistic regression was performed to identify the predictors of ARF during ECMO. A total of 42 children (age, interquartile range [IQR], 13.0 [7.2-29.8] months; weight, IQR, 8.5 [6.7-11.0] kg) after cardiac surgery requiring ECMO were included in this study. The total survival rate was 52.4%, and the incidence of ARF was 40.5%. As the result of univariate analysis, ECMO duration, cardiopulmonary resuscitation, maximum free hemoglobin (FHB) during ECMO, lactate level, and mean blood pressure before initiation of ECMO were entered in multiple logistic regression analysis. In multiple logistic regression analysis, FHB during ECMO (OR 1.136, 95% CI 1.023-1.261) and lactate level before initiation of ECMO (OR 1.602, 95% CI 1.025-2.502) were risk factors for ARF during ECMO after pediatric cardiac surgery. There was a linear correlation between maximum SCr and maximum FHB (Pearson's r = 0.535, P = 0.001). Maximum SCr during ECMO has also a linear correlation with lactate level before initiation of ECMO (Pearson's r = 0.342, P = 0.044). Increased FHB during ECMO and high lactate level before initiation of ECMO were risk factors for ARF during ECMO in pediatric patients after cardiac surgery.

病理解剖で明らかとなった肝内胆管癌からの腫瘍塞栓性肺微小血管障害の1例(Pulmonary tumor thrombotic microangiopathy caused by intrahepatic cholangiocarcinoma)

腫瘍塞栓性肺微小血管障害（pulmonary tumor thrombotic microangiopathy: PTTM）は，肺動脈腫瘍塞栓の特殊な型として報告された新しい疾患概念である。前医にて慢性閉塞性肺疾患に対するリハビリ目的で入院中の71歳男性が，突然の低酸素血症を伴うショックを呈し当院へ救急搬送となった。造影CT検査により肺塞栓症は否定されたが，来院6時間後，急速な酸素化障害から心停止に至りECMO（extracorporeal membranous oxygenation）を導入した。著明な肺高血圧状態にあることが判明したが，治療抵抗性であり入院8日目にECMO離脱困難のまま死亡となった。その後の病理組織診断にて肝内胆管癌由来のPTTMであることが判明した。PTTMは肺動脈内皮の増生を伴う腫瘍塞栓が特徴的な病態で，本症例のように急性増悪する肺高血圧症を認めた際に鑑別を要する病態と考えられる。 Pulmonary tumor thrombotic microangiopathy (PTTM) is a new disease concept that has been reported as a specific type of pulmonary tumor embolism. A 71–year–old man who was undergoing rehabilitation for chronic obstructive pulmonary disease in a different hospital was transported to our hospital due to sudden shock with hypoxia. Initial CT examination was negative for acute pulmonary embolism. Six hours after admission, he went into cardiac arrest following rapid progression of impaired oxygenation, and percutaneous cardiopulmonary support was introduced. Remarkable pulmonary hypertension was identified that was intractable to treatment, and it eventually led to his death 8 days after admission. Subsequent pathological diagnosis revealed the presence of PTTM derived from intrahepatic cholangiocarcinoma. PTTM is characterized by tumor emboli accompanied by endothelial proliferation in the pulmonary vasculature. It should be considered as one differential diagnosis when a patient presents with acute progressive pulmonary hypertension as in this case. 救急領域において，肺高血圧を伴う急性呼吸不全の原因検索は，治療方針の決定のために重要となる。本症例は急速進行性かつ治療抵抗性の肺高血圧を呈し原因不明のまま死に至り，その後の病理組織診断により腫瘍塞栓性肺微小血管障害（pulmonary tumor thrombotic microangiopathy: PTTM）を基盤とする病態であったことが明らかになった1例である。 71歳の男性である。60歳までの40年間の喫煙歴（20本/日）があり，高血圧で内服加療中であった。当院への入院1か月ほど前より労作時呼吸困難が出現したために前医を受診し，慢性閉塞性肺疾患（chronic obstructive pulmonary disease: COPD）と診断され入院となった。入院時の心エコー検査では，異常所見は認められなかった。入院18日目，仰臥位から側臥位への体位変換後に突然の呼吸苦とSpO2の低下を認め，ショック状態となった。血液ガス検査では，pH 7.2，PaO2 71mmHg，PaCO2 21.5mmHg，BE –15mmol/L（O2 8L/minリザーバーマスク投与下）と代謝性アシドーシスを伴う低酸素血症を認めた。輸液負荷と非侵襲的陽圧換気の導入によりショックは一時的に解除された。翌日に精査・集中治療目的に当院へ緊急搬送となった。 当院入院時の身体所見は，血圧115/69mmHg，心拍数115bpmで整，呼吸数26/分，SpO2 96%，腋窩体温37.2°C，意識清明で問診聴取は可能であった。聴診上ラ音は聴取せず，右季肋部に圧痛を認めたが反跳痛や筋性防御は認められなかった。動脈血液ガス分析上では，著しい酸素化の障害と極端な過換気を呈していた（Table 1）。血液検査では，白血球増多を伴わないCRPの軽度上昇と貧血，血小板減少を認めた。間接型優位の高ビリルビン血症が存在し，著明なトランスアミナーゼ，LDHの上昇を伴っていた。ヘモグロビン尿を認め，血清総ハプトグロビン値は測定閾値以下であった。D–ダイマーは増加していた（Table 1）。来院時の胸部X線は気腫性変化を認めるのみであった。胸部CT検査所見は前医と著変なく気管支壁の軽度肥厚と両側肺野の気腫性変化を伴っていたが，主幹肺動脈内に血栓は同定されなかった（Fig. 1a）。腹部CT検査では，肝臓に数mm径の多発性結節影，壁肥厚を伴う胆嚢腫大と周囲の限局性腹水，傍大動脈リンパ節腫脹を認めた（Fig. 1b）。心電図上は異常所見を認めなかった。 (O2 10L/min) (mask with reservoir bag) Findings of CT scan on admission. a: Contrast–enhanced CT imaging of the chest. Filling defect suggesting pulmonary thrombosis/embolism could not be detected. b: Contrast–enhanced CT imaging of the abdomen. The CT showed thickening of the gallbladder wall with surrounding fluid (circle), paraaortic lymphadenopathy (arrow), and multiple low density nodules in the liver (square). c: Ultrasonic cardiography after the resuscitation from cardiac arrest. It revealed that the right ventricle dilated obviously in association with collapse of the left ventricle. RV and LV indicate right ventricle and left ventricle, respectively. 以上より，入院当初は画像所見より急性胆嚢炎からの敗血症性ショックを考慮し，抗菌剤投与とハプトグロビン投与を行い，人工呼吸器管理を視野に入れながら精査・加療方針を立てることになった。その途上，入院約4時間後に突然不穏状態となり，モニター上SpO2の低下が急速に進行し始めた後に血圧が急激に低下し心停止となった。初期波形は心静止であり，速やかに心肺蘇生を開始したが循環虚脱が持続したためECMO（extra–corporeal membranous oxygenation）を導入し，心停止から23分後に心拍再開を得た。 心拍再開直後，再度速やかに造影CT検査を行ったが，主幹肺動脈に塞栓像は認められなかった。心エコー検査では，前医で認めていなかった左室の虚脱を伴う著明な右室の拡張像が認められ（Fig. 1c），高度な肺高血圧症を基礎病態として低酸素血症が急速に進行したために心停止に至ったものと考えられた。しかし，なぜ肺高血圧症が急速に出現したのか，その時点では原因を指摘することができなかった。Swan–Ganzカテーテルを挿入にて高度な肺高血圧状態にあることが確認され，一酸化窒素吸入やミルリノン静注療法を順次開始した（Fig. 2）。第3病日には，胸骨圧迫が原因と考えられる心嚢液貯留を認めたため，心嚢開窓術を施行した。いずれの治療効果も乏しく，平均肺動脈圧 60mmHg前後，中心静脈圧 46mmHg，CI 1.0 L/min/m2とさらに肺高血圧症の進行を認めた。ECMO下にても循環動態維持困難となり，第7病日に死亡確認となった。家族に承諾の上，病理解剖を施行した。 Clinical course after admission. Polygonal lines: systoric and diastolic arterial blood pressure, Crosses: mean pulmonary arterial pressure, Closed circles: cardiac index, NO: nitrogen monoxide, CPA: cardiopulmonary arrest, iv: intravenous injection, V–A ECMO: venous–arterial extracorporeal membrane oxygenation 病理所見上，両肺ともに出血性肺梗塞を認め，肺動脈に関しては毛細血管から径200μm前後の細動脈まで様々な径の血管内に，肺静脈については径1,000μm前後の細静脈内にまで腫瘍塞栓を多発性に認めた（Fig. 3a）。同時に，再疎通を伴う器質化フィブリン血栓を認め（Fig. 3a），血管壁は内膜の線維性肥厚を伴い（Fig. 3b），肺腫瘍塞栓性肺微小血管障害（PTTM）と診断した。肝臓のマクロ所見では，区域を越えて白色調の結節が散在していた。HE染色にて，壊死を伴い腺腔形成の乏しい異型上皮が小胞巣を形成し増生する像が主体で，一部腺腔形成を示す領域が認められた。異型上皮は非腫瘍肝索との連続性を認め，腫瘍胞巣辺縁では置換性発育を示し，腫瘍胞巣内部では既存門脈域構造が保持されていた。腫瘍細胞はCK（cytokeratin）7陽性，CK20陰性，EMA（epithelial membrane antigen）陽性，HSA（hepatocyte specific antigen）陰性であり，HE染色による形態学的特徴と合わせて，肝内胆管癌であることが判明した。大動脈周囲，肝門部，肺門部・縦隔，鎖骨窩の頸部リンパ節には細胆管癌の転移が認められ，さらには占拠された転移腫瘍細胞による骨髄抑制所見を得た。胆嚢には組織学的に明らかな炎症所見は指摘し得なかった。以上より，病理診断によって本病態は肝内胆管癌を基礎に持つPTTMであることが明らかになった。 Pathological findings of the lung and the liver. a, b: Hematoxylin and Eosin staining (a) revealed tumor emboli (black arrow) and thrombus formation (white arrow) followed by recanalization (black arrowhead) in the vessel. In addition, intimal thickening (white arrowheads) was observed by Elastica van Gieson staining (b). c: The images of immunohistochemistry to detect the expression of growth factors related to pathogenesis of PTTM. The embolized tumor cells inside the lung vessel expressed PDGF, Osteopontin, FGF–2, and VEGF, respectively (Magnification×200). 壁肥厚を伴う胆嚢腫大は右心系容量負荷に続発するうっ血によるもの，さらに頻回の輸血を要した貧血と血小板減少は骨髄転移による骨髄抑制が関与していたものであることが判明した。 その後，腫瘍から分泌され血管内膜の線維性肥厚を促進する可能性があるいくつかの因子に関して，病理組織標本を用いて免疫組織化学的に解析したところ，肺病変部の腫瘍細胞においてplatelet–derived growth factor（PDGF），osteopontin（OPN），fibroblast growth factor–2（FGF–2），vascular endothelial growth factor（VEGF）の発現を認めた（Fig. 3c）。一方，保存検体における各因子の血中濃度は正常範囲内であった。 本症例は，急速進行性かつ治療抵抗性の肺高血圧症にて死亡に至り，病理解剖でPTTMとの確定診断に至った一症例である。1987年，Goldhaberらは病理組織学的に筋性動脈以上の径をもつ肺動脈に腫瘍塞栓が存在するものを肺動脈腫瘍塞栓症と定義した 1。これに対し1990年，Herbayらは肺動脈腫瘍塞栓症の特殊型として，pulmonary tumor thrombotic microangiopathyを報告した。血管病変の首座が肺小動脈及び細動脈にあり，血管病変の首座が肺小動脈および細動脈にあるものを新たな疾患概念として確立し，pulmonary tumor thrombotic microangiopathy（PTTM）と呼称した 2。血管内腫瘍塞栓に加えて内膜の線維性肥厚および血栓の器質化と再疎通を伴っていることが特徴的である。本症例においても血管径約200μm以下の細動脈を中心に，これらの組織所見が確認できたことよりPTTMとの診断に至った。 PTTMにおける肺血管内腔狭窄の病因として，腫瘍細胞から分泌されるVEGF 3，FGF，OPN 3，PDGF 4などの成長因子群により内膜の線維細胞増生が誘導される機序が推定されている 5。我々の免疫組織学的な検索においても，肺血管内の腫瘍細胞に同因子群の発現が確認された。これらの成長因子群は血中での上昇が認められず，肺血管内で局所的に作用してPTTMを誘導している可能性が示唆された。 臨床的には呼吸困難，咳嗽，全身倦怠感等を主訴とする予後不良な病態である。山口らは，無症候のうちに微小な肺動脈の腫瘍塞栓を繰り返すことで血管内膜の肥厚や線維化を来し，ある閾値を超えてから肺高血圧症の症状が出現すると示唆している 6。我々が調べた限りでは，本邦におけるPTTMの症例報告は医学中央雑誌で27編30症例存在する。このうち，死亡経過が明記された24例の入院後生存期間は14.9日であった。24例中16例が7日以内に死亡しており，PTTMは入院管理が必要となる病態から死亡に至るまでは急速に病勢が進行していくものと考えられる。本症例では，前医入院1か月ほど前から労作時呼吸困難感が出現しているため，その時期にはPTTMの病態は形成され始めており，低酸素血症が先行する突然の循環虚脱は，既存の肺血管内腔狭窄を基盤にしてびまん性に腫瘍塞栓や血管攣縮が急激に生じて誘導されたものではないかと推測している。 本症例では前医入院中に突然のショックを伴う呼吸不全を呈したことで，まずは急性肺動脈塞栓症を疑ったが造影CT検査により否定された。心エコー検査上では，著明な右心負荷を伴う左心圧排像を示し，左心系への血液流入が抑制されることによるcardiac index（CI）の低下を来していたが，明らかな肺高血圧症を引き起こす左心疾患は指摘できなかった。軽度COPDと診断されていたが，肺炎などCOPDを増悪因子も存在せず，病態が急速進行性であるため慢性呼吸器疾患の進行による肺高血圧症も否定された。一方で本症例では，著明な溶血所見を伴っていたことが特徴的であった。肺高血圧所見を検査上得るまでは，敗血症に伴う一連の全身症状と考えて治療の初期対応を行ったが，結果的には各種培養と病理所見からは本病態における感染症の関与は指摘できなかった。また，自己免疫機序により肺高血圧症，溶血性貧血等の全身症状が急速に出現した可能性も考えられたが，前医までは基盤となる自己免疫疾患を示唆する所見や自己免疫を賦活化させる感染，薬剤投与等のエピソードが無く，実際に特異的な組織学的炎症所見も得られなかった。結果的に，溶血性要因はPTTMを基礎とした肺血管内狭窄による機械的な赤血球破壊によるものと明らかになった。我々が検索した国内外のPTTM症例報告でビリルビン値が記載されている14文献のうち，間接型ビリルビンの上昇を認めた症例は4件あるが，それらが溶血性要因によるものであるかどうかは不明であり，病期の進んだPTTMにおいて赤血球破壊が誘導される現象が特徴的な臨床診断としての指標になり得るのかどうかは今後の検討が必要である。 Herbayらは，300例の固形癌患者の剖検所見において21例（7%）でPTTMが存在していたと報告 2している。PTTMの原発腫瘍としては半数以上が胃癌で，肺癌がそれに続いている 2。我々が医学中央雑誌およびPubMedの国内外の症例報告を検索した限りでは，本症例が初めての肝内胆管癌を起因とするPTTMの報告となる。PTTMを引き起こしやすい癌の細胞特性に何らかの共通性がないかを検索することは，PTTMを制御する薬剤の開発を目指す上でも重要と考えられる。残念ながら，現在PTTMに対する根治的治療法は存在しない。一度進行した肺高血圧の症状を呈すると，本症例のように治療抵抗性に一気に病勢が進行し得る疾患である。末期的なPTTMと診断されれば，その予後を考慮した集中治療方針が決定されることもあるであろう。救急・集中治療において，原因不明の肺高血圧症を認知したら，積極的に胆癌の可能性を疑いPTTMの鑑別を行う必要がある。 急速進行性の肺高血圧症にて死亡に至り，肝内胆管癌由来のPTTMとの病理組織診断を得た1例を経験した。 本論文における利益相反はない。

External validation of scores proposed for estimation of survival probability of patients with severe adult respiratory distress syndrome undergoing extracorporeal membrane oxygenation therapy: a retrospective study.

IntroductionThis study was designed as an external validation of the recently proposed Predicting Death for Severe ARDS on V-V ECMO (PRESERVE) score, The respiratory extracorporeal membrane oxygenation survival prediction (RESP) score and a scoring system developed for externally retrieved patients on extracorporeal membrane oxygenation (ECMO) at our institution. All scores are proposed for the estimation of survival probability after ECMO treatment for severe adult respiratory distress syndrome.MethodsData from 51 patients (2008 to 2013) were analyzed in this retrospective single-center study. A calculation of an adapted PRESERVE score, the RESP score as well as the score developed for externally retrieved ECMO patients was performed.ResultsSeventy one percent of patients received veno-venous (v-v) and 29% venous-arterial (v-a) ECMO support during the study period. Overall survival at 6 months was 55%, with a 61% survival rate for v-v cannulated patients and a 40% survival rate for v-a cannulated patients. The PRESERVE score discriminated survivors and non-survivors with an area under the curve of 0.67 (95% CI 0.52 to 0.82, P = 0.03). Analyzing survival prediction according to cannulation modus, the PRESERVE score and the RESP score significantly predicted survival for patients on v-v ECMO with an area under the curve of 0.75 (95% CI 0.57 to 0.92, P = 0.01) and 0.81 (95% CI 0.67 to 0.95, P = 0.035), respectively, while the scoring system developed for externally retrieved ECMO patients failed to predict survival in our study population. All scores failed to predict mortality for patients on v-a ECMO.ConclusionOur single-center validation confirms that the proposed PRESERVE and RESP score predict survival for patients treated with v-v ECMO for severe adult respiratory distress syndrome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0875-z) contains supplementary material, which is available to authorized users.

Abstract 11973: Clinical Outcome and Predictors of Short-term Mortality in Cardiogenic Shock Treated With Venous-arterial Extracorporeal Membrane Oxygenation: Results From the Japanese Circulation Society Cardiovascular Shock Registry

Introduction: Venous-arterial extracorporeal membrane oxygenation (ECMO) should be considered as a means of rescuing patients with refractory cardiogenic shock and cardiac arrest. Few data are available regarding predicting the outcome of patients with cardiogenic shock treated with ECMO. The aim of this study was to investigate the outcomes of patients with cardiogenic shock assisted by ECMO and to identify the predictors of 30-day mortality. Methods: The Japanese Circulation Society Cardiovascular Shock registry is a prospective, observational, multi-center, cohort study. Between May 2012 and June 2014, a total of 980 patients with cardiovascular shock were enrolled from 82 centers in Japan. Finally, 162 patients (mean age 60.2±14.7 years, 81.5% male) required ECMO and completing 30-day follow-up were analyzed. The primary endpoint was all-cause death at 30 days. Results: Of 162 patients, 80 (49.7%) were shock after return of spontaneous circulation (ROSC) and 102 (63%) had acute coronary syndrome (ACS). The 30-day mortality overall, the non-shock after ROSC group, and the ACS group were 69.1%, 59.3%, and 68.6%, respectively. The causes of death were heart failure in 30 patients (26.8%), multiple organ failure in 49 (43.8%), respiratory failure in 2 (1.8%), sepsis in 2 (1.8%), arrhythmia in 12 (10.7%), neurological death in 8 (7.1%), and others in 9 (7.6%). On multivariate analysis, neurological status on admission (odds ratio 2.188, 95% confidence interval 1.23-3.66, p=0.007) was an independent predictor of all cause death at 30-days. Conclusion: Patients with cardiovascular shock who required ECMO demonstrated high mortality. Neurological status was an independent predictor of 30-day mortality.

Commentary on: Trans-diaphragmatic left ventricular venting during peripheral venous-arterial extracorporeal membrane oxygenation.

Commentary on: Trans-diaphragmatic left ventricular venting during peripheral venous-arterial extracorporeal membrane oxygenation.

TCT-200 ECMO for hemodynamic support in patients with profound cardiogenic shock: experience and outcomes from a large single center

We sought to evaluate the outcomes of ECMO in a variety of clinical settings among patients presenting in cardiogenic shock and/or respiratory failure and underwent emergent venous-arterial (VA) ECMO and/or venous-venous (VV) ECMO placement. We retrospectively analyzed data from 163 consecutive