Anesthetic management including extracorporeal membrane oxygenation therapy of liver transplant recipient with life-threatening hypoxemia -a case report-
A 49 year-old woman (160.0 cm, 94.6 kg) suffering from hepatocellular carcinoma with end-stage hepatitis B liver cirrhosis (model for end stage liver disease [MELD] score 14, Child-Pugh class B) presented for living donor LT. She had hypertension that was well controlled with medications. Her blood type was A, Rh+. The ABO compatible donor was her 25-year-old son (174.5 cm, 86.2 kg).\nAnesthesia was induced with fentanyl (100 µg), thiopental sodium (250 mg), and vecuronium (8 mg), and was maintained with oxygen, air, and desflurane. Neuromuscular block was maintained with atracurium. Hemodynamic monitoring included the right radial and femoral arterial, central and right femoral venous, pulmonary arterial, and capillary wedge pressures, and cardiac output measurements (Vigilance™ monitoring, Edwards Lifesciences, Irvine, CA, USA) through the right internal jugular vein.\nThe surgery proceeded by the piggyback technique, with preservation of caval flow. After the reperfusion of graft liver, right posterior sectionectomy was performed to improve the decreased right hepatic venous flow, a result of a relatively large size of graft liver (recipient original liver weight = 1,049 g, graft volume = 1,500 ml, graft weight = 1,228 g, graft-recipient weight ratio = 1.3%, respectively) and morbid obesity (body mass index: 37.0 kg/m2) of recipient. However, the graft blood flow did not improve, and intractable bleeding occurred at the resection site. Despite rapid volume resuscitation, hypovolemia was aggravated and then cardiac arrest occurred suddenly. Chest compression was started immediately by surgeon, and boluses of epinephrine 1 mg were injected 4 times. Aggressive volume resuscitation was continued using a fluid management system (FMS 2000, Belmont Instrument Corporation, Billerica, MA, USA).\nAfter 8 minutes of the cardiopulmonary resuscitation (CPR), spontaneous circulation was recovered with normal sinus rhythm. Arterial blood gas analysis (ABGA) and coagulation profiles at pre- and post-CPR are shown in and . During CPR, serum potassium level was elevated 4.5 mmol/L to 5.1 mmol/L and serum calcium level decreased 0.62 mmol/L to 0.45 mmol/L. Hematocrit level decreased 16 to 14%. However, significant oozing continued despite surgical hemostasis, and the operator decided to stop surgery for intensive medical treatment and planned a second operation. Thus, after finishing the operation with gauze packing, the patient was transferred to surgical intensive care unit (ICU). During 1,270 minute operation, 33,255 ml of crystalloid, 1,300 ml of 5% albumin, 2,000 ml of colloid, 14 units of leukocyte depleted red blood cell, 6 units of leukocyte depleted platelet concentrate, 984 ml of cell saver blood, 8 units of fresh frozen plasma, and 3 units of cryoprecipitate were infused. Urine output was 1,520 ml, and estimated blood loss was about 10,000 ml.\nAfter the operation, the patient's condition deteriorated, with metabolic acidosis with pH < 7.2 and azotemia with creatinine level over 2.0 mg/dl due to ongoing graft failure and intractable bleeding despite aggressive management. Severe hypoxemia persisted despite a fraction of inspired oxygen (FiO2) = 1.0 with mechanical ventilation set as 6 ml/kg of tidal volume (for ideal body weight), 30 breaths/minute, and increasing positive end-expiratory pressure (PEEP) of up to 10 cmH2O ().\nChest radiography revealed pulmonary congestion () and echocardiography was performed to rule out cardiogenic pulmonary edema, but cardiac physiology, function, and structure were in normal without any abnormalities. As anuria developed 7 hours after the end of the operation, continuous renal replacement therapy (CRRT) was started via the right femoral vein following a continuous VV hemodiafiltration protocol. Brain tomography was obtained before CRRT, but there was no definite abnormal finding.\nBecause of the failure of conventional ventilatory support, and in the hope of liver retransplantation, the decision was made to initiate VV ECMO as a rescue device. Although she suffered hypovolemic arrest during first LT, post-operative echocardiography revealed normal heart function, physiology and structures. Therefore, the cardiologist in our ECMO team suggested that there was no need of cardiac support with ECMO. The existing central cannula and Swan-Ganz catheter was removed. A 28 French (Fr) drainage cannula (DLP®, Medtronic Inc., Minneapolis, MN, USA) was placed in the right femoral vein, and a 21 Fr Medtronic return cannula was placed in the right internal jugular vein. A CAPIOX emergent bypass system and circuit (EBS®, Terumo Inc., Tokyo, Japan) was primed with 470 ml of normal saline. The CAPIOX EBS oxygenator kit contains 1.8 m2 of membrane lung surface. CRRT was continued through ECMO circuit (). VV ECMO circulation was maintained at 4.0-5.0 L/min (2.0-2.5 L/min/m2) with 5-6 L/min sweep gas flow at 100% oxygen. Heparin was not used because the patient had a severe bleeding tendency, and 500 IU of antithrombin was injected intravenously every 6 hour (Post-LT care protocol of our center). Activated clotting time (ACT) was measured every 5 min for the initial 15 min then 240 min thereafter. The ACT was maintained between 120-180 s throughout. After ECMO treatment, the patient's condition improved to 95% SpO2 with a FiO2 of 0.3-0.4 at the ventilator and 1.0 at ECMO ().\nAbout 24 hours after ECMO application, the patient was transferred to the operating room to receive deceased donor LT. The warm ischemic time of the donated liver was 41 minutes, and the cold ischemic time was 446 minutes.\nPerioperative ABGA profiles and coagulation profiles are shown in and , respectively. The preoperative chest radiograph showed a sustained pulmonary congestion and bilateral pleural effusions. Her MELD score at secondary LT was 30 with ECMO and CRRT support. Considering her condition with a high risk of massive bleeding along with the planned ECMO application during the operation, we decided to discontinue CRRT during the operation and restart after the operation depending on her condition.\nWhen the patient arrived at operating room, she was already intubated. The patient was monitored as during the previous operation except for femoral arterial blood pressure, pulmonary arterial pressure, and cardiac output monitoring, because there were no suitable cannulation site for these devices due to ECMO cannula and generalized edema. To maintain body temperature during anesthesia, core temperature was continuously monitored via mid-esophageal temperature probe. Administered fluid was heated by FMS 2000, and every peripheral vascular access was removed to prevent infusion of cold fluid. A warm blanket was spread on the operating table, and a humidifier (Hygroster, Covidien, Mansfield, MA, USA) was applied at the ventilatory circuit. The patient's limbs were covered with cotton roll and vinyl wrap and room temperature was maintained within 24.0 to 28.0℃. Anesthetic management followed our hospital's LT protocol.\nHer SpO2 was stable ranged from 97 to 100% with a FiO2 of 0.5 at the ventilator (pressure controlled ventilation; tidal volume of 3 to 4 ml/kg (about 5 to 6 ml/kg for ideal body weight), respiratory rate of 8 to 12 breaths/min, and PEEP of 5 to 10 cmH2O) and 1.0 at ECMO (Circuit flow of 4 to 5 L/min and gas sweep of 5 to 6 L/min). Her body temperature was maintained within the range of 35.8 to 36.1℃.\nCompartment syndrome was a concern during abdominal closure, so surgery was finished without suturing the abdominal wall. Total administered volume included crystalloid 7,400 ml, colloid 2,530 ml, 5% dextrose water 450 ml, cell saver autotransfusion 792 ml, leukocyte-depleted red blood cell 11 units, fresh frozen plasma 8 units, plateletpheresis 2 units, cryoprecipitate 8 units for 350 minutes. There was no severe oozing or acute massive bleeding on operation field. Hematocrit level was maintained over 24% during operation without rapid volume resuscitation. No hypotensive episode occurred below mean arterial pressure of 70 mmHg. Urine was not excreted during the entire operation.\nAfter the surgery, sedation was maintained with continuous infusion of midazolam and fentanyl. CRRT was restarted and ECMO was continued. Her body temperature was maintained within the range of 35.3 to 37.0℃ with forced-air warmer (Bair Hugger®, Augustine Medical, Eden Prairie, MN, USA), heated humidifier and circuit (MR850, Fisher and Paykel Healthcare, Auckland, New Zealand), and pre-warmed fluid. To check the return of consciousness, Glasgow coma scale was tested every 4 hours. Pupil size, light reflex, limb movement, and orientation were also checked to judge neurologic abnormalities. Pupil dilatation did not occur and light reflex was normal, but the other exams were meaningless during ECMO support because continuous sedation and muscular relaxation therapy with cisatracurium were sustained for the opened laparotomy wound.\nAfter 64 hours following ECMO support, and 32 hours after secondary LT, arterial oxygen saturation () and chest roentgenogram () were improved significantly. Based on sonography and improved coagulopathy (), the graft appeared functional. Hemodynamic stability was also achieved without high dose inotropic support (0.7 mcg/kg/min of norepinephrine was infused continuously before secondary LT, and tapered to 0.05 mcg/kg/min at before ECMO weaning). Recovery from hepatic failure was the most important factor to decide weaning, because our patient's respiratory failure was closely related to hepatic failure. To initiate weaning, in the first stage, we reduced bypass flow from 4.0-5.0 L/min to 3.0 L/min. And in the second stage, for 7 hours of close monitoring and ABGA at every 2 hours after start weaning, we reduced oxygen flow to ECMO to zero gradually, and FiO2 for ventilator was increased from 0.4 to 0.6 over an hour. Two hours after the second stage, ABGAs performed twice per hour showed appropriate oxygenation, then ECMO was removed from the patient. shows ABGA profiles for both during and after ECMO weaning. Comparing just before and after the ECMO support, PaO2/FiO2 ratio improved from 56.9 to 117.2. The PaCO2 level was similar to before ECMO support, but ventilatory demand was significantly decreased. Subsequently, PaO2/FiO2 stabilized at SpO2 over 90% with FiO2 0.6. The laparotomy wound closure was done 5 days after the surgery.\nHowever, liver congestion was noted one day after the wound closure and hepatic drainage failed. Surgical decompression was performed, but stenosis at intrahepatic IVC developed. Although stenting for the stenosis was performed 5 days after the surgical decompression, graft failure was not improved. In addition, long-term use of high dose vasopressor led to both leg necrosis and further sepsis. After stopping fentanyl and cisatracurium infusion, the patient showed continuous eye opening for a half-day and low grade motor responses, but no further improvement of consciousness. The patient expired 24 days after the second LT due to multi-organ failure caused by combined graft failure and uncontrolled sepsis.