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RotaFlow and CentriMag Extracorporeal Membrane Oxygenation Support Systems as Treatment Strategies for Refractory Cardiogenic Shock Antonio Loforte, M.D., Ph.D.,* Emanuele Pilato, M.D.,* Sofia Martin Suarez, M.D., Ph.D.,* Gianluca Folesani, M.D.,* Giuliano Jafrancesco, M.D.,* Sebastiano Castrovinci, M.D.,* Francesco Grigioni, M.D., Ph.D.,y and Giuseppe Marinelli, M.D., Ph.D.* *Department of Cardiovascular Surgery and Transplantation, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy; and yDepartment of Cardiology and Transplantation, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy ABSTRACT Background: RotaFlow and Levitronix CentriMag veno-arterial extracorporeal membrane oxygenation (ECMO) support systems have been investigated as treatment for refractory cardiogenic shock (CS). Methods: Between 2004 and 2012, 119 consecutive adult patients were supported on RotaFlow (n = 104) or CentriMag (n = 15) ECMO at our institution (79 men; age 57.3 W 12.5 years, range:19–78 years). Indications for support were: failure to wean from cardiopulmonary bypass in the setting of postcardiotomy (n = 47) and primary graft failure (n = 26); post-acute myocardial infarction CS (n = 11); acute myocarditis (n = 3); and CS on chronic heart failure (n = 32). Results: A central ECMO setting was established in 64 (53.7%) patients while peripherally in 55 (46.2%). Overall mean support time was 10.9 W 8.7 days (range:1–43 days). Forty-two (35.2%) patients died on ECMO. Overall success rate, in terms of survival on ECMO (n = 77), weaning from mechanical support (n = 51;42.8%) and bridge to heart transplantation (n = 26;21.8%), was 64.7%. Sixty-eight (57.1%) patients were successfully discharged. Stepwise logistic regression identified blood lactate level and CK-MB relative index at 72 h after ECMO initiation, and number of packed red blood cells (PRBCs) transfused on ECMO as significant predictors of mortality (p = 0.011, odds ratio [OR] = 2.48; 95% confidence interval [CI] = 1.11–3.12; p = 0.012, OR = 2.81, 95% CI = 1.02–2.53; and p = 0.012, OR = 1.94; 95% CI = 1.02–5.21; respectively). Central ECMO population had a higher rate of continuous veno-venous hemofiltration (CVVH) need and bleeding events when compared with the peripheral setting. Conclusions: Patients with a poor hemodynamic status may benefit by rapid insertion of veno-arterial ECMO. The blood lactate level, CK-MB relative index and PRBCs transfused should be strictly monitored during ECMO support. doi: 10.1111/jocs.12480 (J Card Surg 2015;30:201–208) Veno-arterial extracorporeal membrane oxygenation (ECMO) provides temporary cardiorespiratory support to patients (pts) with severe but potentially reversible cardiac or respiratory deterioration refractory to standard therapeutic modalities.1 Despite the advent of newer Conflict of interest: The authors acknowledge no conflict of interestin the submission. Disclosure statement: There is no funding source or relevant interest to declare. Address for correspondence: Antonio Loforte, M.D., Ph.D., Department of Cardiovascular Surgery and Transplantation, S. OrsolaMalpighi Hospital, Bologna University, Via Massarenti n.9, 40138 Bologna, Italy. Fax: þ39 051 345990; e-mail: [email protected]
ventricular assist devices (VADs) that are more suitable for long-term support, ECMO is simple to establish and cost-effective to operate. We report our experience in using the RotaFlow (Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany) and the Levitronix CentriMag (Levitronix LCC, Waltham, MA, USA) centrifugal pumps in the setting of central or peripheral veno-arterial ECMO as treatment for pts with primary or postcardiotomy cardiogenic shock (CS). Extracorporeal membrane oxygenation system Between 2004 and 2006, the ECMO circuit consisted of a polymethylpentene (PMP) oxygenator, Quadrox D
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(Maquet, Jostra Medizintechnik AG), and a centrifugal pump, Rotaflow (Maquet, Jostra Medizintechnik AG) (n ¼ 28). Since 2007, the recent PLS (Permanent Life Support; Maquet, Jostra Medizintechnik AG) ECMO circuit was used and combined, traditionally, with the RotaFlow pump (n ¼ 76)2–4 or adapted for the Levitronix CentriMag (Levitronix LLC) (n ¼ 15).5–8 A heater-cooler (Stockert, Munchen, Germany) was added to the venoarterial ECMO circuit. The cannulation was performed centrally in 64 (53.7%) patients, using the right atrium, through its lateral wall as access, and the left atrium, between the right pulmonary veins as access, for venous drainage. The employed cannulae were two 28 Fr wire-reinforced angled veno-atrial cannula (Jostra Venous Catheter OD, Maquet Cardiopulmonary AG, Hirrlingen, Germany) for both atria. The outflow cannula was always positioned into the ascending aorta (straight aortic perfusion cannula, Edwards Lifesciences LLC, Irvine, CA, USA; 22 Fr or 24 Fr). All cannulas were secured with pledgeted reinforced pursestring prolene sutures, tunneled through subcostal incisions to allow the chest closure and then connected to the circuit, avoiding air in the system. Peripheral veno-arterial cannulation was performed in 55 (46.2%) patients by usage of an arterial return cannula, DLP Biomedicus 15 Fr–19 Fr (mostly 17 Fr) (Medtronic Inc., Minneapolis, MN, USA) which was inserted into the femoral artery and a venous drainage cannula, DLP Biomedicus 17 Fr–23 Fr (Medtronic Inc.) which was inserted into the femoral vein.4 Both insertions were performed using the Seldinger technique after anterior vessel wall exposure and secured with pledgeted reinforced pursestring prolene sutures. The Quadrox D oxygenator2–4 has a PMP hydrophobic hollowfiber diffusion membrane with an effective surface area of 1.8 m2, which allows long-term high gas exchange performance; the oxygen transfer capacity and the carbon dioxide transfer capacity are 288 ml/min and 230 ml/min, respectively; the pressure drop across the in and out lines of the device does not exceed 40 mmHg at 4 L/min; the priming volume is 250 ml. This oxygenator is compact with a decreased heat exchange surface area of the membrane (0.6 m2), thus reducing the risk of clot formation. The RotaFlow is a centrifugal pump with a low prime volume (32 ml) which can provide high blood flow until 10 L/min.2,4 This pump features a peg-top one-point sapphire bearing that lowers friction substantially without any metal shaft or seal. Its spiral housing ensures an optimized flow ratio with no stagnant zones. The pump rotor is magnetically suspended and four flowing channels are generated inside the housing of the pump. These allow a continuous laminar flow with minimal turbulence and a reduced risk of hemolysis. The Levitronix CentriMag blood pumping system has been specially designed for extracorporeal circulatory support applications as cardiopulmonary bypass (CPB) or uni- or biventricular assistance.5–8 The CentriMag motor is based on ‘‘bearingless’’ technology that
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combines the drive, magnetic bearing, and rotor into a single unit. The rotor is suspended and rotated by eight L-shaped iron cores (four pairs) with drive and control winding together. The rotor position and rotation are continuously controlled by a feedback control system in radial directions. Another impeller motion is passively suspended with bias flux between rotor and stator. The pump system consists of a single-use disposable polycarbonate pump head (priming volume: 31 ml, connectors: 0.375 inch inlet/outlet ports), motor/ bearing drive unit (diameter height ¼ 87 70 mm), cannulae, and a bedside controller. This system can generate flows up to 10 L/minute, and in Europe the system is licensed for use for 30 days. Recently the CentriMag pump has been also adopted successfully for an ECMO support setting by different institutions.6–8 In the circuit, tubings and oxygenator are coated with Bioline Coating (Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany).2–4 Recombinant human albumin is adsorbed on the extrinsic surface and acts as receptor of heparin. Covalent bonds and ionic interaction occur between the heparin molecules and the albumin. By this treatment, all the surfaces in contact with the blood have highly stable covalent and ionic links with heparin. This coating provides high hemocompatibility thus minimizing the activation of platelets, coagulation cascade, and complement. The circuit was primed with saline and the priming procedure usually needed 4–5 min. In the novel adopted circuit, PLS,2–4 the Quadrox D oxygenator has the housing reinforced with glass fibers to increase the mechanical resistance and the polyvinyl chloride (PVC) of the circuit is DEHP-free (Bis 2-ethylhexyl-phthalate). The PLS has been certified for a support period of 14 days (DEKRA Intertek Certification as a notified body of European Union, in accordance with the Directive 93/42/European Community). Patients Between January 2004 and December 2012, 8.171 adult patients underwent cardiac operations, mainly valvular procedures, at our institution. During the same period, 119 patients (1.45%) required veno-arterial peripheral or central ECMO support for primary or postcardiotomy CS (Tables 1 and 2). A central ECMO setting was established in 64 (53.7%) patients while peripherally in 55 (46.2%). Inclusion criteria for veno-arterial ECMO support to treat primary refractory heart failure (HF) and CS at our institution are the following: acute myocardial infarction (AMI); acute decompensation of end-stage dilated cardiomyopathy (DCMP); acute myocarditis; high-risk percutaneous transluminal coronary angioplasty (PTCA); failure to wean from cardiopulmonary bypass (CPB) after surgery. Patients were excluded according to the following criteria: severe peripheral arteriopathy; severe and chronic renal failure; terminal malignancy; irreversible or severe degenerative brain diseases; trauma. Extracorporeal membrane oxygenation support was installed mostly in the operating room (n ¼ 105) and
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TABLE 1 Demographic and Preimplant Clinical Parameters of the Different Cohorts of Patients Supported by Veno-Arterial ECMO Postcardiotomy (n = 47)
Donor Graft Failure (n = 26)
Mean age (years) 60.3 (40–78) 49.1 (23–63) Male gender (n,%) 35 (74.4%) 10 (38.4%) BSA (m2) 1.8 (1.75–1.88) 1.8 (1.78–1.88) Etiology Coronary disease (n,%) 33 (70.2%) – Valvular disease (n,%) 28 (59.5%) – DCMP (n,%) – – Preoperative LVEF (%) 48.3 (35–75) – Number of deaseased coronaries 2.4 (2–3) – Previous cardiac operation 19 (40.4%) 9 (34.6%) Logistic EuroSCORE (%) 25.5 (10–45) – CPB time 202.4 (48–368) 227.3 (196–266) Ischemic time 117.2 (65–199) 195.5 (177–210) 31 (28–45) 32 (26–45) SAPS II score* 32 (20–45) 30 (20–38) Inotropic score* mSAP (mmHg) 63 (50–65) 64.9 (50–68) SvO2 (%) 48 (40–55) 54 (48–58) Lactate level (mg/dl) 13.6 (6.7–18.1) 12.5 (5.7–17.2) CPR (n,%) 8 (17.02%) 1 (3.8%) CPR time (minutes) 28.1 (16–62) – IABP (n, %) 11 (23.4%) – Mechanical ventilation (n, %) 47 (100%) 26 (100%)
Acute on Chronic HF (n = 32)
Post-AMI (n = 11)
Acute Miocarditis (n = 3)
64.8 (40–71) 52.6 (19–55) 48.2 (44–55) 11 (100%) 23 (71.8%) – 1.9 (1.85–1.95) 1.82 (1.78–1.86) 1.81 12 (100%) – – – 2.3 (2–3)
11 (34.3%) 8 (25%) 13 (40.6%) – –
36 35 62.9 47 14.8 6 31.5 11 11
– – – (28–50) (20–50) (48–65) (40–55) (7.7–18.1) (54.5%) (11–53) (100%) (100%)
2.6 (2–3) 13 (40.6%) – – – 31 (15–41) 32 (15–38) 60.9 (50–70) 48 (45–55) 12.9 (6.7–17.1) 2 (6.2%) 25.5 (15–55) 21 (65.2%) 12 (37.5%)
31 30 62.9 47 12.5 1 3
– – – – – – – – – (28–45) (20–38) (48–65) (40–55) (5.7–17.2) – – (33.3%) (100%)
All values are presented as median and range or as percentage. AMI, acute myocardial infarction; BSA, body surface area; CBP, cardiopulmonary bypass; CPR, cardiopulmonary resuscitation; DCMP, dilative cardiomyopathy; ECMO, extracorporeal membrane oxygenation; HF, heart failure; IABP, intra-aortic balloon pump; LVEF, left ventricular ejection fraction; mSAP, mean systolic arterial pressure; SAPS, simplified acute physiology score; SvO2, mixed venous oxygen saturation. * Definition is given by the same author elsewhere.4,5
rarely in the intensive care unit (n ¼ 14, peripheral ECMO). In the studied population the vital status immediately before ECMO placement, as traditionally evaluated before any short-term mechanical support device placement by the same author,4,5 was documented using the simplified acute physiology score (SAPS) II and the inotropic score (Table 1). Berlin intra-aortic balloon pump (IABP) score for mechanical support initiation9 was adopted for ECMO support triggering. Written informed consent was obtained from all patients. This study was conducted in accordance with the International Conference on Harmonization, Harmonized Tripartite Guidelines for Good Clinical Practice and the ethical principles laid down in the Declaration of Helsinki after approval by the Institutional Review Board (IRB). Extracorporeal membrane oxygenation management The ECMO blood flow was adjusted during the first 24–48 h to maintain a cardiac index of 2.6 L/min/m2, mixed venous oxygen saturation (SvO2) around 70%, and mean arterial pressure (MAP) of 60–65 mmHg. Before cannulation, all patients received an intravenous heparin bolus (40–80 units/kg); during ECMO support the heparin was administered continuously to achieve an activated clotting time (ACT) of 140–160
seconds and a prothrombin time value of 50–70. Infusion of antithrombin III (AT III) was required if the AT III serum level was below 80%. In patients with a motionless left ventricle, small doses of inotropes (dobutamine) were given to obtain a minimal ventricular contraction avoiding clot formation inside the left ventricle and avoid pulmonary edema. All ECMO support was conducted under normothermia. Close chested examinations by transesophageal echo were done to assess both left and right ventricle function daily. For peripheral cannulation, a continuous-wave Doppler image of the tibial artery flow and pulsatility was acquired every two days to evaluate distal leg perfusion. In six patients, due to the absence of both anterior and posterior tibial artery flow and/or a mean pressure of the superficial femoral artery 100 ml/h by the drains, during the first three postoperative hours, associated with hemodynamic instability and/or tamponade needing >10 PRBCs Units and surgical reexploration (within 1 h of diagnosis).
Central ECMO setting Peripheral ECMO setting RotaFlow ECMO CentriMag ECMO ECMO time (dd) ECMO > 6 days IABP on ECMO (n,%) IABP time (dd) Intubation time (dd) Hospital stay (dd) Creatinine >3.5 (mg/100 ml) CVVH CVVH time (days) Bleeding** Transfusion PRBCs PLT units FFP (1000 ml/unit) Pulmonary infection Bilirubin >15 (mg/100 ml) PLT count PFH (mg/dl) CK-MB relative index (%)* MOF Sepsis Brain death (cerebral hemorrage) Survived on ECMO Central setting (n ¼ 41, 64.06%) Peripheral setting (n ¼ 36, 65.4%) Weaned from ECMO Central setting (n ¼ 27, 42.1%) Peripheral setting (n ¼ 24, 43.6%) Died on ECMO Central setting (n ¼ 23, 35.9%) Peripheral setting (n ¼ 19, 34.5%) Htx Discharged Central setting (n ¼ 37, 57.8%) Peripheral setting (n ¼ 31, 56.3%) 1-year survival
Postcardiotomy (n = 47)
TABLE 2 Outcome on Veno-Arterial ECMO Support
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given when platelet count was less than 50.000– 60.000. Mechanical ventilation was continued throughout mechanical support. An IABP was employed in all patients with the aim of reducing the left ventricle afterload and distension to avoid pulmonary edema, improving the coronary perfusion and maintaining a pulsatile flow.9 No attempts to wean off ECMO were usually considered during the first 72 h. Criteria for weaning include an SvO2 70%, a hematocrit of 28–30%, the absence of bleeding or tamponade, a left ventricular ejection fraction (EF) 35% with an aortic time–velocity integral (VTI) >10 cm on echocardiography, the absence of left heart distension, good contraction of the right ventricle (EF >40%) with the absence of moderate to severe tricuspid regurgitation, normal blood lactate levels (80 ml/h). A gradual weaning by reducing the ECMO flow by 10% every ~12 h was our main strategy, together with close transesophageal echocardiography and SwanGanz catheter examinations. Once an ECMO flow of 1.5 L/min/m2 is reached, the pump flow was reduced at 0.5 L/min/m2 for ~30 min using an IABP set at 1:1. If the hemodynamics in terms of systemic arterial pressure (mean pressure >60 mmHg), LV contractility (EF >35%), central venous pressure (10–15 mmHg), wedge pressure (10–15 mmHg), and SvO2 (>70%) showed no significant changes without the addition of new inotropes, the heparin was stopped, and ECMO support was removed in the operating room within the next 1 h or, more rarely, at bedside (n ¼ 8). In all patients, the IABP support was maintained for at least five days after ECMO removal. Statistical analysis Descriptive statistics are expressed as the means standard deviation or as the medians and range. A p-value less than 0.05 was deemed to indicate statistical significance. Categorical variables are presented as percentages, and the x2-test was used to compare them. Analysis of variance for repeatedmeasures was employed for numerical variables. Continuous variables were evaluated using Student’s t-test for independent variables. Univariate analysis was used as a screening process to identify predictor variables; those with p < 0.05 were selected. Stepwise logistic regression analysis was applied to determine the independent predictors of 30-day mortality. All analyses were performed using SPSS for Windows, release 11.5 (SPSS Inc., Chicago, IL, USA). RESULTS The mean age was 57.3 12.5 years (range: 19–78 years) and 79 patients (66.3%) were males. The RotaFlow pump was used in 104 patients (87.3%), while the CentriMag in 15 (12.6%), and both groups were adapted for a veno-arterial central or peripheral ECMO support setting. The overall mechanical average
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support time was 10.9 8.7 days (range: 1–43 days), 10.9 9.8 days (range: 1–43 days) for peripheral ECMO and 10.6 8.5 days (range: 3–32 days) for central ECMO. Overall Overall survival on mechanical support was 64.7% (n ¼ 68 [65.3%] for RotaFlow; n ¼ 9 [60%] for CentriMag). Fifty-one [42.8%] patients were weaned off ECMO (n ¼ 43 [41.3%] for RotaFlow; n ¼ 8 [53.3%] for CentriMag) while 42 [35.2%] died during ECMO support (n ¼ 36 [34.6%] for RotaFlow; n ¼ 6 [40%] for CentriMag) due to multiple organ failure [MOF), which was mostly associated with sepsis and brain death (Tables 1 and 2). Among patients who survived on ECMO, sixty-eight [57.1%) were discharged (n ¼ 61 [58.6%] for RotaFlow; n ¼ 7 [46.6%] for CentriMag). Twenty-six (21.8%) patients were successfully bridged to heart transplantation (Htx) (n ¼ 25 [24.3%] for RotaFlow; n ¼ 1 [6.6%] for CentriMag) after an average time of ECMO support of 9.8 8.6 days (range: 3–18 days). Among these transplanted patients, six (acute on chronic HF cohort) re-required veno-arterial ECMO support for graft failure after Htx at the time of weaning from CPB and further successful ECMO weaning and removal, and overall 23 patients were successfully discharged home. Forty-six [38.6%] patients required ECMO to treat a primary CS (n ¼ 40 [38.4%] for RotaFlow; n ¼ 6 [40%] for CentriMag). Eleven of them, referred mostly from other different institutions, had a large myocardial infarction (left main, n ¼ 8) and were already treated by primary percutaneous multivessel transluminal coronary angioplasty (PTCA) (n ¼ 9 [8.6%] for RotaFlow; n ¼ 2 [13.3%] for CentriMag). Three patients had an acute myocarditis (n ¼ 3 [2.8%] RotaFlow) and 32 patients, who were already on the waiting list for Htx, had an acute decompensation on chronic HF due to end-stage DCMP (n ¼ 29 [27.8%] for RotaFlow; n ¼ 3 [20%] for CentriMag). Forty-seven [39.4%] patients received ECMO support after cardiac surgery procedures due to failure to wean from CPB (n ¼ 39 [37.5%] for RotaFlow; n ¼ 8 [53.3%] for CentriMag). Postcardiotomy procedures included: combined coronary artery bypass grafting (CABG) and mitral valve replacement in 14; combined CABG and aortic valve replacement in 10; mitral valve replacement in eight; CABG in five; Bentall procedure in five; combined ascending aorta and aortic arch replacement in three; and mitral valve replacement in two. Additionally, twenty-six patients [21.8%] required ECMO support (n ¼ 25 [24.03%] for RotaFlow; n ¼ 1 [6.6%] for CentriMag) to treat an early primary graft failure after Htx. Seventeen patients [14.2%] received ECMO (n ¼ 14 [13.4%] for RotaFlow; n ¼ 3 [20%] for CentriMag) during cardiopulmonary resuscitation (CPR) with a mean time CPR of 30.3 13.1 min (range, 10–62 min). The preoperative risk profile and postoperative parameters are listed in Tables 1 and 2. An IABP was inserted into all of the patients before ECMO support according to the Hausmann et al.9 IABP score for mechanical support initiation. There was no impairment of the native lungs in all patients before ECMO.
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In all patients, blood lactate, CK-MB, and CK-MB relative index as the ratio of CK-MB to total CK were measured during overall ECMO support. All of the evaluated parameters showed a significant reduction during the first 72 h of support (Tables 1, 2 and 3). The blood lactate level 72 h after ECMO initiation (p < 0.01), the MB isoenzyme of creatine kinase (CK-MB) 72 h after ECMO initiation (p ¼ 0.01), and the CK-MB relative index 72 h after ECMO initiation (p < 0.001) had statistically significant differences between survivors and nonsurvivors on ECMO (Table 3). Logistic regression analysis revealed blood lactate levels (3 mmol/l) at 72 h after initiation of ECMO and CKMB relative index 72 h after ECMO initiation to be a significant predictor of mortality on ECMO support (p ¼ 0.011, OR ¼ 2.48; 95% CI ¼ 1.11–3.12; p ¼ 0.012, OR ¼ 2.81, 95% CI ¼ 1.02–2.53). All patients were transfused (Table 2). A hemoglobin level of >10 mg/dl would not be expected in critically ill patients, and is a higher level than needs to be maintained for appropriate perfusion. The patients who died had a higher number of red blood cell transfusions (p < 0.01), a higher number of platelet (p ¼ 0.03), and a higher number of units of fresh frozen plasma (FFP) transfusions (p ¼ 0.02) (Table 3). The stepwise logistic regression analysis revealed that number of PRBCs transfused are independent predictors of mortality during ECMO support (p ¼ 0.012, OR ¼ 1.94; 95% CI ¼ 1.02–5.21). Platelet counts were measured and a moderate reduction was observed (overall, average 236.4 81.7 K/ml, before ECMO, vs. 133.4 91.7 K/ml, already at 72 h of ECMO support [p ¼ 0.01], but with no significant further reduction at the overall average time of ECMO support and no significant difference
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between survivors and non-survivors). No cases of heparin induced thrombocytopenia (HIT) on ECMO occurred and fondaparinux was adopted only during IABP support before ECMO in case of a platelet count less than 100 K/ml.10 Peripheral complications of femoral access included leg ischemia (n ¼ 3, 5.4%) which required immediate distal perfusion catheter insertion, and femoral site infection (n ¼ 3, 5.4%). No isolated mediastinitis occurred in the central ECMO population. Central ECMO population had more bleeders (54.6% vs. 38.1%, p ¼ 0.01) with higher need for blood transfusions (PRBCs: 14.9 11.2 vs. 9.7 4.6, p ¼ 0.02; PLT units: 20.3 15.7 vs. 15.2 6.6, p ¼ 0.02; FFP 1000 ml/ unit: 8.3 6.1 vs. 4.7 3.8, p ¼ 0.03), and higher rate of continuous veno-venous hemofiltration (CVVH) (64.06% vs. 32.7%, p ¼ 0.01) when compared with the peripheral ECMO population. There were no cases of pulmonary hemorrage. DISCUSSION The novel material polymethylpentene (PMP), which we adopted, is likely the key to the success of the last generation of oxygenators and ECMO systems in terms of high gas-exchange efficiency in a small change surface, low prime volume, low pressure gradient, and no plasma leakage for periods of more than seven days. The PMP Quadrox D oxygenator and the entire ECMO circuit had to be changed in 14 [11.7%] patients (n ¼ 11 for RotaFlow; n ¼ 3 for CentriMag) with aggressive sepsis (postcardiotomy and post-AMI cohorts) with difficult anticoagulation ECMO management, leading to clinical hemolysis (defined as an increase of more than twofold in LDH and free hemoglobin in plasma compared with the values on
TABLE 3 Comparison of the Survivors and Nonsurvivors Variables
Age (years) Female gender Lactate level (mg/dl) before ECMO CPB time (min) in postcardiotomy cohort Aortic cross-clamping time (min) in postcardiotomy cohort CPR before ECMO Inotropic score before ECMO* Intubation time (days) on ECMO MOF on ECMO PRBCs on ECMO PLT units on ECMO FFP (1000 ml/unit) on ECMO Blood lactate level (mg/dL) 72 h after ECMO initiation CK-MB relative index (%) 72 h after ECMO initiation** CK-MB (U/L) 72 h after ECMO initiation PFH (mg/dL) 72 h after ECMO initiation
Survivors (n = 77)
Nonsurvivors (n = 42)
p-value
49 9.8 18 (23.3%) 12.7 3.7 172.5 92.6 88.2 55.4 3 (3.8%) 11.2 3.3 9.9 8.2 2 (2.5%) 8.4 5.5 14.8 7.8 3.5 3.8 2.2 1.41 7.4 3.52 146.3 136.3 33.4 11.2
66.1 12.1 22 (52.3%) 30.5 27.3 234 122.2 142.5 76.1 14 (53.8%) 34.6 7.2 19.9 7.2 27 (64.2%) 22.6 13.4 26.5 16.8 9.8 8.4 7.8 5.42 20.7 11.4 358.4 231.2 94.2 15.6
0.04 0.01
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RotaFlow and CentriMag Extracorporeal Membrane Oxygenation Support Systems as Treatment Strategies for Refractory Cardiogenic Shock Antonio Loforte, M.D., Ph.D.,* Emanuele Pilato, M.D.,* Sofia Martin Suarez, M.D., Ph.D.,* Gianluca Folesani, M.D.,* Giuliano Jafrancesco, M.D.,* Sebastiano Castrovinci, M.D.,* Francesco Grigioni, M.D., Ph.D.,y and Giuseppe Marinelli, M.D., Ph.D.* *Department of Cardiovascular Surgery and Transplantation, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy; and yDepartment of Cardiology and Transplantation, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy ABSTRACT Background: RotaFlow and Levitronix CentriMag veno-arterial extracorporeal membrane oxygenation (ECMO) support systems have been investigated as treatment for refractory cardiogenic shock (CS). Methods: Between 2004 and 2012, 119 consecutive adult patients were supported on RotaFlow (n = 104) or CentriMag (n = 15) ECMO at our institution (79 men; age 57.3 W 12.5 years, range:19–78 years). Indications for support were: failure to wean from cardiopulmonary bypass in the setting of postcardiotomy (n = 47) and primary graft failure (n = 26); post-acute myocardial infarction CS (n = 11); acute myocarditis (n = 3); and CS on chronic heart failure (n = 32). Results: A central ECMO setting was established in 64 (53.7%) patients while peripherally in 55 (46.2%). Overall mean support time was 10.9 W 8.7 days (range:1–43 days). Forty-two (35.2%) patients died on ECMO. Overall success rate, in terms of survival on ECMO (n = 77), weaning from mechanical support (n = 51;42.8%) and bridge to heart transplantation (n = 26;21.8%), was 64.7%. Sixty-eight (57.1%) patients were successfully discharged. Stepwise logistic regression identified blood lactate level and CK-MB relative index at 72 h after ECMO initiation, and number of packed red blood cells (PRBCs) transfused on ECMO as significant predictors of mortality (p = 0.011, odds ratio [OR] = 2.48; 95% confidence interval [CI] = 1.11–3.12; p = 0.012, OR = 2.81, 95% CI = 1.02–2.53; and p = 0.012, OR = 1.94; 95% CI = 1.02–5.21; respectively). Central ECMO population had a higher rate of continuous veno-venous hemofiltration (CVVH) need and bleeding events when compared with the peripheral setting. Conclusions: Patients with a poor hemodynamic status may benefit by rapid insertion of veno-arterial ECMO. The blood lactate level, CK-MB relative index and PRBCs transfused should be strictly monitored during ECMO support. doi: 10.1111/jocs.12480 (J Card Surg 2015;30:201–208) Veno-arterial extracorporeal membrane oxygenation (ECMO) provides temporary cardiorespiratory support to patients (pts) with severe but potentially reversible cardiac or respiratory deterioration refractory to standard therapeutic modalities.1 Despite the advent of newer Conflict of interest: The authors acknowledge no conflict of interestin the submission. Disclosure statement: There is no funding source or relevant interest to declare. Address for correspondence: Antonio Loforte, M.D., Ph.D., Department of Cardiovascular Surgery and Transplantation, S. OrsolaMalpighi Hospital, Bologna University, Via Massarenti n.9, 40138 Bologna, Italy. Fax: þ39 051 345990; e-mail: [email protected]
ventricular assist devices (VADs) that are more suitable for long-term support, ECMO is simple to establish and cost-effective to operate. We report our experience in using the RotaFlow (Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany) and the Levitronix CentriMag (Levitronix LCC, Waltham, MA, USA) centrifugal pumps in the setting of central or peripheral veno-arterial ECMO as treatment for pts with primary or postcardiotomy cardiogenic shock (CS). Extracorporeal membrane oxygenation system Between 2004 and 2006, the ECMO circuit consisted of a polymethylpentene (PMP) oxygenator, Quadrox D
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(Maquet, Jostra Medizintechnik AG), and a centrifugal pump, Rotaflow (Maquet, Jostra Medizintechnik AG) (n ¼ 28). Since 2007, the recent PLS (Permanent Life Support; Maquet, Jostra Medizintechnik AG) ECMO circuit was used and combined, traditionally, with the RotaFlow pump (n ¼ 76)2–4 or adapted for the Levitronix CentriMag (Levitronix LLC) (n ¼ 15).5–8 A heater-cooler (Stockert, Munchen, Germany) was added to the venoarterial ECMO circuit. The cannulation was performed centrally in 64 (53.7%) patients, using the right atrium, through its lateral wall as access, and the left atrium, between the right pulmonary veins as access, for venous drainage. The employed cannulae were two 28 Fr wire-reinforced angled veno-atrial cannula (Jostra Venous Catheter OD, Maquet Cardiopulmonary AG, Hirrlingen, Germany) for both atria. The outflow cannula was always positioned into the ascending aorta (straight aortic perfusion cannula, Edwards Lifesciences LLC, Irvine, CA, USA; 22 Fr or 24 Fr). All cannulas were secured with pledgeted reinforced pursestring prolene sutures, tunneled through subcostal incisions to allow the chest closure and then connected to the circuit, avoiding air in the system. Peripheral veno-arterial cannulation was performed in 55 (46.2%) patients by usage of an arterial return cannula, DLP Biomedicus 15 Fr–19 Fr (mostly 17 Fr) (Medtronic Inc., Minneapolis, MN, USA) which was inserted into the femoral artery and a venous drainage cannula, DLP Biomedicus 17 Fr–23 Fr (Medtronic Inc.) which was inserted into the femoral vein.4 Both insertions were performed using the Seldinger technique after anterior vessel wall exposure and secured with pledgeted reinforced pursestring prolene sutures. The Quadrox D oxygenator2–4 has a PMP hydrophobic hollowfiber diffusion membrane with an effective surface area of 1.8 m2, which allows long-term high gas exchange performance; the oxygen transfer capacity and the carbon dioxide transfer capacity are 288 ml/min and 230 ml/min, respectively; the pressure drop across the in and out lines of the device does not exceed 40 mmHg at 4 L/min; the priming volume is 250 ml. This oxygenator is compact with a decreased heat exchange surface area of the membrane (0.6 m2), thus reducing the risk of clot formation. The RotaFlow is a centrifugal pump with a low prime volume (32 ml) which can provide high blood flow until 10 L/min.2,4 This pump features a peg-top one-point sapphire bearing that lowers friction substantially without any metal shaft or seal. Its spiral housing ensures an optimized flow ratio with no stagnant zones. The pump rotor is magnetically suspended and four flowing channels are generated inside the housing of the pump. These allow a continuous laminar flow with minimal turbulence and a reduced risk of hemolysis. The Levitronix CentriMag blood pumping system has been specially designed for extracorporeal circulatory support applications as cardiopulmonary bypass (CPB) or uni- or biventricular assistance.5–8 The CentriMag motor is based on ‘‘bearingless’’ technology that
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combines the drive, magnetic bearing, and rotor into a single unit. The rotor is suspended and rotated by eight L-shaped iron cores (four pairs) with drive and control winding together. The rotor position and rotation are continuously controlled by a feedback control system in radial directions. Another impeller motion is passively suspended with bias flux between rotor and stator. The pump system consists of a single-use disposable polycarbonate pump head (priming volume: 31 ml, connectors: 0.375 inch inlet/outlet ports), motor/ bearing drive unit (diameter height ¼ 87 70 mm), cannulae, and a bedside controller. This system can generate flows up to 10 L/minute, and in Europe the system is licensed for use for 30 days. Recently the CentriMag pump has been also adopted successfully for an ECMO support setting by different institutions.6–8 In the circuit, tubings and oxygenator are coated with Bioline Coating (Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany).2–4 Recombinant human albumin is adsorbed on the extrinsic surface and acts as receptor of heparin. Covalent bonds and ionic interaction occur between the heparin molecules and the albumin. By this treatment, all the surfaces in contact with the blood have highly stable covalent and ionic links with heparin. This coating provides high hemocompatibility thus minimizing the activation of platelets, coagulation cascade, and complement. The circuit was primed with saline and the priming procedure usually needed 4–5 min. In the novel adopted circuit, PLS,2–4 the Quadrox D oxygenator has the housing reinforced with glass fibers to increase the mechanical resistance and the polyvinyl chloride (PVC) of the circuit is DEHP-free (Bis 2-ethylhexyl-phthalate). The PLS has been certified for a support period of 14 days (DEKRA Intertek Certification as a notified body of European Union, in accordance with the Directive 93/42/European Community). Patients Between January 2004 and December 2012, 8.171 adult patients underwent cardiac operations, mainly valvular procedures, at our institution. During the same period, 119 patients (1.45%) required veno-arterial peripheral or central ECMO support for primary or postcardiotomy CS (Tables 1 and 2). A central ECMO setting was established in 64 (53.7%) patients while peripherally in 55 (46.2%). Inclusion criteria for veno-arterial ECMO support to treat primary refractory heart failure (HF) and CS at our institution are the following: acute myocardial infarction (AMI); acute decompensation of end-stage dilated cardiomyopathy (DCMP); acute myocarditis; high-risk percutaneous transluminal coronary angioplasty (PTCA); failure to wean from cardiopulmonary bypass (CPB) after surgery. Patients were excluded according to the following criteria: severe peripheral arteriopathy; severe and chronic renal failure; terminal malignancy; irreversible or severe degenerative brain diseases; trauma. Extracorporeal membrane oxygenation support was installed mostly in the operating room (n ¼ 105) and
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TABLE 1 Demographic and Preimplant Clinical Parameters of the Different Cohorts of Patients Supported by Veno-Arterial ECMO Postcardiotomy (n = 47)
Donor Graft Failure (n = 26)
Mean age (years) 60.3 (40–78) 49.1 (23–63) Male gender (n,%) 35 (74.4%) 10 (38.4%) BSA (m2) 1.8 (1.75–1.88) 1.8 (1.78–1.88) Etiology Coronary disease (n,%) 33 (70.2%) – Valvular disease (n,%) 28 (59.5%) – DCMP (n,%) – – Preoperative LVEF (%) 48.3 (35–75) – Number of deaseased coronaries 2.4 (2–3) – Previous cardiac operation 19 (40.4%) 9 (34.6%) Logistic EuroSCORE (%) 25.5 (10–45) – CPB time 202.4 (48–368) 227.3 (196–266) Ischemic time 117.2 (65–199) 195.5 (177–210) 31 (28–45) 32 (26–45) SAPS II score* 32 (20–45) 30 (20–38) Inotropic score* mSAP (mmHg) 63 (50–65) 64.9 (50–68) SvO2 (%) 48 (40–55) 54 (48–58) Lactate level (mg/dl) 13.6 (6.7–18.1) 12.5 (5.7–17.2) CPR (n,%) 8 (17.02%) 1 (3.8%) CPR time (minutes) 28.1 (16–62) – IABP (n, %) 11 (23.4%) – Mechanical ventilation (n, %) 47 (100%) 26 (100%)
Acute on Chronic HF (n = 32)
Post-AMI (n = 11)
Acute Miocarditis (n = 3)
64.8 (40–71) 52.6 (19–55) 48.2 (44–55) 11 (100%) 23 (71.8%) – 1.9 (1.85–1.95) 1.82 (1.78–1.86) 1.81 12 (100%) – – – 2.3 (2–3)
11 (34.3%) 8 (25%) 13 (40.6%) – –
36 35 62.9 47 14.8 6 31.5 11 11
– – – (28–50) (20–50) (48–65) (40–55) (7.7–18.1) (54.5%) (11–53) (100%) (100%)
2.6 (2–3) 13 (40.6%) – – – 31 (15–41) 32 (15–38) 60.9 (50–70) 48 (45–55) 12.9 (6.7–17.1) 2 (6.2%) 25.5 (15–55) 21 (65.2%) 12 (37.5%)
31 30 62.9 47 12.5 1 3
– – – – – – – – – (28–45) (20–38) (48–65) (40–55) (5.7–17.2) – – (33.3%) (100%)
All values are presented as median and range or as percentage. AMI, acute myocardial infarction; BSA, body surface area; CBP, cardiopulmonary bypass; CPR, cardiopulmonary resuscitation; DCMP, dilative cardiomyopathy; ECMO, extracorporeal membrane oxygenation; HF, heart failure; IABP, intra-aortic balloon pump; LVEF, left ventricular ejection fraction; mSAP, mean systolic arterial pressure; SAPS, simplified acute physiology score; SvO2, mixed venous oxygen saturation. * Definition is given by the same author elsewhere.4,5
rarely in the intensive care unit (n ¼ 14, peripheral ECMO). In the studied population the vital status immediately before ECMO placement, as traditionally evaluated before any short-term mechanical support device placement by the same author,4,5 was documented using the simplified acute physiology score (SAPS) II and the inotropic score (Table 1). Berlin intra-aortic balloon pump (IABP) score for mechanical support initiation9 was adopted for ECMO support triggering. Written informed consent was obtained from all patients. This study was conducted in accordance with the International Conference on Harmonization, Harmonized Tripartite Guidelines for Good Clinical Practice and the ethical principles laid down in the Declaration of Helsinki after approval by the Institutional Review Board (IRB). Extracorporeal membrane oxygenation management The ECMO blood flow was adjusted during the first 24–48 h to maintain a cardiac index of 2.6 L/min/m2, mixed venous oxygen saturation (SvO2) around 70%, and mean arterial pressure (MAP) of 60–65 mmHg. Before cannulation, all patients received an intravenous heparin bolus (40–80 units/kg); during ECMO support the heparin was administered continuously to achieve an activated clotting time (ACT) of 140–160
seconds and a prothrombin time value of 50–70. Infusion of antithrombin III (AT III) was required if the AT III serum level was below 80%. In patients with a motionless left ventricle, small doses of inotropes (dobutamine) were given to obtain a minimal ventricular contraction avoiding clot formation inside the left ventricle and avoid pulmonary edema. All ECMO support was conducted under normothermia. Close chested examinations by transesophageal echo were done to assess both left and right ventricle function daily. For peripheral cannulation, a continuous-wave Doppler image of the tibial artery flow and pulsatility was acquired every two days to evaluate distal leg perfusion. In six patients, due to the absence of both anterior and posterior tibial artery flow and/or a mean pressure of the superficial femoral artery 100 ml/h by the drains, during the first three postoperative hours, associated with hemodynamic instability and/or tamponade needing >10 PRBCs Units and surgical reexploration (within 1 h of diagnosis).
Central ECMO setting Peripheral ECMO setting RotaFlow ECMO CentriMag ECMO ECMO time (dd) ECMO > 6 days IABP on ECMO (n,%) IABP time (dd) Intubation time (dd) Hospital stay (dd) Creatinine >3.5 (mg/100 ml) CVVH CVVH time (days) Bleeding** Transfusion PRBCs PLT units FFP (1000 ml/unit) Pulmonary infection Bilirubin >15 (mg/100 ml) PLT count PFH (mg/dl) CK-MB relative index (%)* MOF Sepsis Brain death (cerebral hemorrage) Survived on ECMO Central setting (n ¼ 41, 64.06%) Peripheral setting (n ¼ 36, 65.4%) Weaned from ECMO Central setting (n ¼ 27, 42.1%) Peripheral setting (n ¼ 24, 43.6%) Died on ECMO Central setting (n ¼ 23, 35.9%) Peripheral setting (n ¼ 19, 34.5%) Htx Discharged Central setting (n ¼ 37, 57.8%) Peripheral setting (n ¼ 31, 56.3%) 1-year survival
Postcardiotomy (n = 47)
TABLE 2 Outcome on Veno-Arterial ECMO Support
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given when platelet count was less than 50.000– 60.000. Mechanical ventilation was continued throughout mechanical support. An IABP was employed in all patients with the aim of reducing the left ventricle afterload and distension to avoid pulmonary edema, improving the coronary perfusion and maintaining a pulsatile flow.9 No attempts to wean off ECMO were usually considered during the first 72 h. Criteria for weaning include an SvO2 70%, a hematocrit of 28–30%, the absence of bleeding or tamponade, a left ventricular ejection fraction (EF) 35% with an aortic time–velocity integral (VTI) >10 cm on echocardiography, the absence of left heart distension, good contraction of the right ventricle (EF >40%) with the absence of moderate to severe tricuspid regurgitation, normal blood lactate levels (80 ml/h). A gradual weaning by reducing the ECMO flow by 10% every ~12 h was our main strategy, together with close transesophageal echocardiography and SwanGanz catheter examinations. Once an ECMO flow of 1.5 L/min/m2 is reached, the pump flow was reduced at 0.5 L/min/m2 for ~30 min using an IABP set at 1:1. If the hemodynamics in terms of systemic arterial pressure (mean pressure >60 mmHg), LV contractility (EF >35%), central venous pressure (10–15 mmHg), wedge pressure (10–15 mmHg), and SvO2 (>70%) showed no significant changes without the addition of new inotropes, the heparin was stopped, and ECMO support was removed in the operating room within the next 1 h or, more rarely, at bedside (n ¼ 8). In all patients, the IABP support was maintained for at least five days after ECMO removal. Statistical analysis Descriptive statistics are expressed as the means standard deviation or as the medians and range. A p-value less than 0.05 was deemed to indicate statistical significance. Categorical variables are presented as percentages, and the x2-test was used to compare them. Analysis of variance for repeatedmeasures was employed for numerical variables. Continuous variables were evaluated using Student’s t-test for independent variables. Univariate analysis was used as a screening process to identify predictor variables; those with p < 0.05 were selected. Stepwise logistic regression analysis was applied to determine the independent predictors of 30-day mortality. All analyses were performed using SPSS for Windows, release 11.5 (SPSS Inc., Chicago, IL, USA). RESULTS The mean age was 57.3 12.5 years (range: 19–78 years) and 79 patients (66.3%) were males. The RotaFlow pump was used in 104 patients (87.3%), while the CentriMag in 15 (12.6%), and both groups were adapted for a veno-arterial central or peripheral ECMO support setting. The overall mechanical average
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support time was 10.9 8.7 days (range: 1–43 days), 10.9 9.8 days (range: 1–43 days) for peripheral ECMO and 10.6 8.5 days (range: 3–32 days) for central ECMO. Overall Overall survival on mechanical support was 64.7% (n ¼ 68 [65.3%] for RotaFlow; n ¼ 9 [60%] for CentriMag). Fifty-one [42.8%] patients were weaned off ECMO (n ¼ 43 [41.3%] for RotaFlow; n ¼ 8 [53.3%] for CentriMag) while 42 [35.2%] died during ECMO support (n ¼ 36 [34.6%] for RotaFlow; n ¼ 6 [40%] for CentriMag) due to multiple organ failure [MOF), which was mostly associated with sepsis and brain death (Tables 1 and 2). Among patients who survived on ECMO, sixty-eight [57.1%) were discharged (n ¼ 61 [58.6%] for RotaFlow; n ¼ 7 [46.6%] for CentriMag). Twenty-six (21.8%) patients were successfully bridged to heart transplantation (Htx) (n ¼ 25 [24.3%] for RotaFlow; n ¼ 1 [6.6%] for CentriMag) after an average time of ECMO support of 9.8 8.6 days (range: 3–18 days). Among these transplanted patients, six (acute on chronic HF cohort) re-required veno-arterial ECMO support for graft failure after Htx at the time of weaning from CPB and further successful ECMO weaning and removal, and overall 23 patients were successfully discharged home. Forty-six [38.6%] patients required ECMO to treat a primary CS (n ¼ 40 [38.4%] for RotaFlow; n ¼ 6 [40%] for CentriMag). Eleven of them, referred mostly from other different institutions, had a large myocardial infarction (left main, n ¼ 8) and were already treated by primary percutaneous multivessel transluminal coronary angioplasty (PTCA) (n ¼ 9 [8.6%] for RotaFlow; n ¼ 2 [13.3%] for CentriMag). Three patients had an acute myocarditis (n ¼ 3 [2.8%] RotaFlow) and 32 patients, who were already on the waiting list for Htx, had an acute decompensation on chronic HF due to end-stage DCMP (n ¼ 29 [27.8%] for RotaFlow; n ¼ 3 [20%] for CentriMag). Forty-seven [39.4%] patients received ECMO support after cardiac surgery procedures due to failure to wean from CPB (n ¼ 39 [37.5%] for RotaFlow; n ¼ 8 [53.3%] for CentriMag). Postcardiotomy procedures included: combined coronary artery bypass grafting (CABG) and mitral valve replacement in 14; combined CABG and aortic valve replacement in 10; mitral valve replacement in eight; CABG in five; Bentall procedure in five; combined ascending aorta and aortic arch replacement in three; and mitral valve replacement in two. Additionally, twenty-six patients [21.8%] required ECMO support (n ¼ 25 [24.03%] for RotaFlow; n ¼ 1 [6.6%] for CentriMag) to treat an early primary graft failure after Htx. Seventeen patients [14.2%] received ECMO (n ¼ 14 [13.4%] for RotaFlow; n ¼ 3 [20%] for CentriMag) during cardiopulmonary resuscitation (CPR) with a mean time CPR of 30.3 13.1 min (range, 10–62 min). The preoperative risk profile and postoperative parameters are listed in Tables 1 and 2. An IABP was inserted into all of the patients before ECMO support according to the Hausmann et al.9 IABP score for mechanical support initiation. There was no impairment of the native lungs in all patients before ECMO.
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In all patients, blood lactate, CK-MB, and CK-MB relative index as the ratio of CK-MB to total CK were measured during overall ECMO support. All of the evaluated parameters showed a significant reduction during the first 72 h of support (Tables 1, 2 and 3). The blood lactate level 72 h after ECMO initiation (p < 0.01), the MB isoenzyme of creatine kinase (CK-MB) 72 h after ECMO initiation (p ¼ 0.01), and the CK-MB relative index 72 h after ECMO initiation (p < 0.001) had statistically significant differences between survivors and nonsurvivors on ECMO (Table 3). Logistic regression analysis revealed blood lactate levels (3 mmol/l) at 72 h after initiation of ECMO and CKMB relative index 72 h after ECMO initiation to be a significant predictor of mortality on ECMO support (p ¼ 0.011, OR ¼ 2.48; 95% CI ¼ 1.11–3.12; p ¼ 0.012, OR ¼ 2.81, 95% CI ¼ 1.02–2.53). All patients were transfused (Table 2). A hemoglobin level of >10 mg/dl would not be expected in critically ill patients, and is a higher level than needs to be maintained for appropriate perfusion. The patients who died had a higher number of red blood cell transfusions (p < 0.01), a higher number of platelet (p ¼ 0.03), and a higher number of units of fresh frozen plasma (FFP) transfusions (p ¼ 0.02) (Table 3). The stepwise logistic regression analysis revealed that number of PRBCs transfused are independent predictors of mortality during ECMO support (p ¼ 0.012, OR ¼ 1.94; 95% CI ¼ 1.02–5.21). Platelet counts were measured and a moderate reduction was observed (overall, average 236.4 81.7 K/ml, before ECMO, vs. 133.4 91.7 K/ml, already at 72 h of ECMO support [p ¼ 0.01], but with no significant further reduction at the overall average time of ECMO support and no significant difference
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between survivors and non-survivors). No cases of heparin induced thrombocytopenia (HIT) on ECMO occurred and fondaparinux was adopted only during IABP support before ECMO in case of a platelet count less than 100 K/ml.10 Peripheral complications of femoral access included leg ischemia (n ¼ 3, 5.4%) which required immediate distal perfusion catheter insertion, and femoral site infection (n ¼ 3, 5.4%). No isolated mediastinitis occurred in the central ECMO population. Central ECMO population had more bleeders (54.6% vs. 38.1%, p ¼ 0.01) with higher need for blood transfusions (PRBCs: 14.9 11.2 vs. 9.7 4.6, p ¼ 0.02; PLT units: 20.3 15.7 vs. 15.2 6.6, p ¼ 0.02; FFP 1000 ml/ unit: 8.3 6.1 vs. 4.7 3.8, p ¼ 0.03), and higher rate of continuous veno-venous hemofiltration (CVVH) (64.06% vs. 32.7%, p ¼ 0.01) when compared with the peripheral ECMO population. There were no cases of pulmonary hemorrage. DISCUSSION The novel material polymethylpentene (PMP), which we adopted, is likely the key to the success of the last generation of oxygenators and ECMO systems in terms of high gas-exchange efficiency in a small change surface, low prime volume, low pressure gradient, and no plasma leakage for periods of more than seven days. The PMP Quadrox D oxygenator and the entire ECMO circuit had to be changed in 14 [11.7%] patients (n ¼ 11 for RotaFlow; n ¼ 3 for CentriMag) with aggressive sepsis (postcardiotomy and post-AMI cohorts) with difficult anticoagulation ECMO management, leading to clinical hemolysis (defined as an increase of more than twofold in LDH and free hemoglobin in plasma compared with the values on
TABLE 3 Comparison of the Survivors and Nonsurvivors Variables
Age (years) Female gender Lactate level (mg/dl) before ECMO CPB time (min) in postcardiotomy cohort Aortic cross-clamping time (min) in postcardiotomy cohort CPR before ECMO Inotropic score before ECMO* Intubation time (days) on ECMO MOF on ECMO PRBCs on ECMO PLT units on ECMO FFP (1000 ml/unit) on ECMO Blood lactate level (mg/dL) 72 h after ECMO initiation CK-MB relative index (%) 72 h after ECMO initiation** CK-MB (U/L) 72 h after ECMO initiation PFH (mg/dL) 72 h after ECMO initiation
Survivors (n = 77)
Nonsurvivors (n = 42)
p-value
49 9.8 18 (23.3%) 12.7 3.7 172.5 92.6 88.2 55.4 3 (3.8%) 11.2 3.3 9.9 8.2 2 (2.5%) 8.4 5.5 14.8 7.8 3.5 3.8 2.2 1.41 7.4 3.52 146.3 136.3 33.4 11.2
66.1 12.1 22 (52.3%) 30.5 27.3 234 122.2 142.5 76.1 14 (53.8%) 34.6 7.2 19.9 7.2 27 (64.2%) 22.6 13.4 26.5 16.8 9.8 8.4 7.8 5.42 20.7 11.4 358.4 231.2 94.2 15.6
0.04 0.01
