LIVER TRANSPLANTATION 21:410–414, 2015
LETTER FROM THE FRONTLINE
Extracorporeal Membrane Oxygenation as a Rescue Device for Postreperfusion Cardiac Arrest During Liver Transplantation Received October 16, 2014; accepted November 19, 2014.
TO THE EDITORS: Intraoperative cardiac arrest is a dreaded complication of liver transplantation with a poor outcome.1,2 The majority of cardiac arrests occur during the neohepatic phase, especially during reperfusion, and most are caused by either postreperfusion syndrome or pulmonary thromboembolic events.2 Almost 20% of patients with intraoperative cardiac arrest cannot be successfully resuscitated and do not regain a spontaneous rhythm and circulation. Of those who regain a spontaneous rhythm and circulation with cardiopulmonary resuscitation (CPR), more than 12% will not survive the surgery. The mortality of intraoperative cardiac arrest increases exponentially with the duration of CPR. If spontaneous rhythm and circulation are not restored rapidly, the prognosis is usually poor. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been used as an extension of CPR in many clinical scenarios with varying success. We describe a successful case of the use of VA-ECMO to treat postreperfusion cardiac arrest and discuss practical aspects of using VA-ECMO as rescue CPR during liver transplantation. CASE REPORT A 61-year-old man with hepatitis B cirrhosis and hepatocellular carcinoma underwent deceased donor liver transplantation. He had previously undergone transarterial chemoembolization of the hepatocellular carcinoma and esophageal banding for esophageal varices. His physiologic Model for End-Stage Liver Disease score was 8 (serum creatinine 5 0.66 mg/dL, total bilirubin 5 0.9 mg/dL, and international normalized ratio 5 1.2). He was well compensated and reported good exercise tolerance with no symptoms of cardiac disease. A transthoracic echocardiogram 3 months before surgery demonstrated a left ventricular ejection fraction of 60% to 65%, normal biventricular
systolic function, and no valvular pathologies. There was no evidence of wall motion abnormalities on a technetium-99m sestamibi pharmacologic stress test, which was also performed 3 months before surgery. A suitable standard criteria donor organ was identified (a 25-year-old woman who had a subarachnoid hemorrhage). The liver graft was procured and coldpreserved in a standard fashion without a perfusion circuit. The cold ischemia time of the graft was 5 hours 15 minutes, and the warm ischemia time was 47 minutes. The recipient was brought into the operating room, and after induction of general anesthesia, left radial and right femoral arterial catheters were placed along with a right internal jugular introducer with a pulmonary artery catheter without any complications. Initial intraoperative laboratory values were unremarkable. The dissection phase proceeded without complications and without the need for blood products. The patient tolerated clamping of the inferior vena cava and removal of the native liver with only low-dose vasopressor support (norepinephrine at 1 mg/minute and vasopressin at 1 U/hour). During the anhepatic phase, the patient remained hemodynamically stable and required slowly increasing doses of vasopressors with peak doses of norepinephrine of 6 mg/minute and vasopressin of 4 U/hour. The arterial blood gas analyses before reperfusion and at other time points are listed in Table 1. After complete caval clamping and removal of the native liver, the new graft was implanted with a bicaval end-to-end anastomosis and an end-to-end portal vein anastomosis. During this time, 2 g of magnesium and 1 g of calcium were administered. Caval and portal vein clamps were then removed. During the first 1 to 2 minutes after reperfusion of the transplanted liver, the blood pressure remained stable with initially decreased vasopressor requirements. However, within the first 4 minutes after reperfusion, the blood pressure decreased gradually, and this was
Potential conflict of interest: Nothing to report. Address reprint requests to Gebhard Wagener, M.D., Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, P&S Box 46 (PH-5), 630 West 168th Street, New York, NY 10032-3784. Telephone: 212-305-6494; FAX: 212-305-2182; E-mail: gw72@cumc. columbia.edu DOI 10.1002/lt.24056 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION. DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
C 2015 American Association for the Study of Liver Diseases. V
6.3 6.8 9.2 7.0 9.2 1.26 1.23 1.16 1.04 1.25 6.7 5.9 4.4 3.8 3.2 145 137 141 142 141
4.9 1.96 4.4 >170
6.2 1.36 4.1 138
12.6 9.8 8.5 1.18 1.03 1.20 3.3 3.3 4.0 138 139 138
15.8 11.2 20.5 25.8 27.0 29.6 217.6 24.0 3.6 2.2 32 39 34 28 28 7.31 7.06 7.39 7.57 7.56
>490 >490 >490 >490 347
29.5 7.9 26 7.66
271
18.1 26.7 32 7.36
164
27.1 24.3 24.0 3.2 0.4 20.7 >490 274 260 38 36 39 7.46 7.44 7.40
(mg/dL) (mmol/L) (mmol/L) (mmol/L) (mmol/L) (%) (mmol/L) (mmol/L) (mm Hg) (mm Hg) pH
Anesthesia start 100 0.8 100 1.0 100 1.9 Reperfusion 99 4.2 Start CPR 100 11.5 Start ECMO 100 >18.0 100 >18.0 100 10.0 100 5.9 >99.6 5:48 6:50 8:38 9:34 10:08 10:21 10:32 10:47 10:53 10:55 11:21 12:18 14:05 15:35
Time
Hemoglobin Ionized
calcium Na Lactate Concentration
Bicarbonate Base
of O2 of CO2
Excess
Partial Pressure Partial Pressure
TABLE 1. Blood Gas Analysis and Electrolytes During the Case
K O2
Saturation
Concentration
LIVER TRANSPLANTATION, Vol. 21, No. 3, 2015
LETTER FROM THE FRONTLINE 411
followed by increases in the pulmonary artery and central venous pressures. At this time, the patient remained in sinus rhythm with no apparent arrhythmias or other electrocardiogram changes. Despite escalating doses of phenylephrine and epinephrine, the hemodynamic parameters deteriorated, and the patient developed profound hypotension and bradycardia. CPR was initiated 24 minutes after reperfusion, initially externally and then internally through an incision of the subcardiac diaphragm. At this time, the patient developed ventricular fibrillation that did not respond to 5 attempts of internal defibrillation. During CPR, a total of 5 mg of intravenous epinephrine, 300 mg of amiodarone in 150-mg doses, 2 U of vasopressin, 100 mEq of sodium-bicarbonate in 50mEq doses, and 1 mg of intracardiac epinephrine were administered. After approximately 5 minutes of CPR, the cardiac perfusion team was called to initiate VA-ECMO. Throughout the cardiac arrest, internal CPR was very effective with evidence of good perfusion on the arterial blood pressure tracing. Therefore, no further attempts at defibrillation were made to avoid interruption of CPR. The patient remained in ventricular fibrillation until VA-ECMO was initiated. Ice was placed on the patient’s head as neuroprotection. At 21 minutes after the cardiac arrest, cardiac surgery completed the open cannulation of the right femoral vein (23F cannula) and left femoral artery (17F cannula). VA-ECMO was initiated after 30,000 U of heparin had been given. Approximately 10 minutes after the initiation of VAECMO, the cardiac rhythm spontaneously converted from ventricular fibrillation to a slow junctional rhythm. Pacing wires were placed into the myocardium through the incision in the diaphragm. We placed a transesophageal echocardiogram shortly after the initiation of VA-ECMO that showed an ejection fraction of 5% with moderate to severe left ventricular dilation. To decompress the dilated left ventricle, a cannula was placed into the left ventricular apex for drainage and connected to the extracorporeal membrane oxygenation (ECMO) circuit. An 8F catheter was inserted into the left superficial femoral artery cannulation and connected to the arterial side of the VA-ECMO circuit to maintain perfusion to the leg. Milrinone at 0.25 mg/kg/minute and 20 ppm of inhaled nitric oxide were initiated. At this time, the potassium level was 6.7 mEq, and it was treated with insulin and dextrose. As vasopressor requirements decreased, the liver, which initially became swollen and edematous when the central venous pressure was high, appeared less congested and viable. The decision was made to complete the liver transplant procedure with an end-toend hepatic artery anastomosis and choledochocholedochostomy. Hemostasis was adequate at the end of the operation, but the abdomen was packed because there was concern about bleeding with heparinization for VA-ECMO. After the left ventricular drain and pacing wires were secured and a Jackson-Pratt drain was
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placed in the pericardium, the abdomen was closed, and the patient was transferred to the intensive care unit. The total estimated blood loss was 4000 mL; he received 9 U of packed red blood cells, 5 U of fresh frozen plasma, and 130 mL of cryoprecipitate during the surgery. Throughout the cardiac arrest and while on VA-ECMO, the patient had good urine output of at least 1 mL/kg/hour. In the intensive care unit, he required multiple boluses of fluid and blood products to maintain VAECMO flow. A repeat transesophageal echocardiogram on postoperative day 1 demonstrated improvement of left and right ventricular function with an estimated left ventricular ejection fraction of 25% to 30%. Even though the liver function was satisfactory and the coagulation profile was only mildly abnormal, the patient continued to bleed from the left femoral arterial cannulation site and the Jackson-Pratt drain in the pericardium. At 48 hours after the initial surgery, he returned to the operating room; the VA-ECMO was successfully decannulated, and the abdominal packing was removed. The further postoperative course was unremarkable. His trachea was extubated 3 days after the transplant, and he was neurologically completely intact. He left the hospital 20 days after the initial surgery to go home and remained in good health with good graft function 3 months later. A transthoracic echocardiogram just before discharge found normal left and right ventricular function. DISCUSSION This case report demonstrates that VA-ECMO can be lifesaving in patients who experience cardiac arrest during liver transplantation. A large retrospective study found that intraoperative cardiac arrest during liver transplantation occurs in approximately 5.5% of cases. Intraoperative cardiac arrest was associated with a 29.4% intraoperative and 44.1% 30-day mortality. Approximately one-third of intraoperative cardiac arrests in this cohort were caused by reperfusion syndrome, one-third were caused by pulmonary thromboembolism, and only 7.4% were caused by hyperkalemia. The success of CPR decreases exponentially with the duration of CPR, even if occasional good outcomes have been reported after prolonged CPR. VA-ECMO is increasingly used as a rescue mode to maintain perfusion during CPR. It allows time to correct reversible causes of cardiac arrest or await spontaneous recovery of circulation or allows the placement of a longer term support system. It should be noted that the use of VA-ECMO in this situation provides precious time but does not necessarily correct the underlying cause of the cardiac arrest. The success of rescue VA-ECMO after cardiac arrest depends on the age, cause of cardiac arrest, and duration and effectiveness of CPR. A prospective study that compared patients with external CPR with patients who received VA-ECMO after 10 minutes of external CPR found a survival benefit with the use of
LIVER TRANSPLANTATION, March 2015
Figure. 1. Extracorporeal membrane oxygenation circuit: Blood flows from the venous cannula to the centrifugal pump to the oxygenator and then back through the arterial cannula to the patient.
VA-ECMO.3 Survival is poor in older patients and in cases in which VA-ECMO is initiated after more than 30 minutes of CPR.4 Postreperfusion cardiac arrest during liver transplantation may be well suited for rescue VA-ECMO and potentially better than external CPR. Direct access to the heart and open internal massage through the diaphragm can provide better perfusion while VA-ECMO circuit and cannulas are being prepared. Adequate blood pressure and perfusion during CPR will reduce the risk of potential sequelae of cardiac arrest and will improve the chances of recovery. Recent studies have indicated that frequent and prolonged interruptions of CPR for defibrillations, for example, may have deleterious effects.5,6 For this reason, no further attempts at defibrillation were made once the decision was made to proceed with VAECMO. Liver transplant teams may be familiar with venovenous ECMO because this has been used to enable liver transplantation in patients with severe hypoxia, for example, due to hepatopulmonary syndrome.7,8 VA-ECMO, however, is conceptually and technically different, and familiarity with this procedure may facilitate its appropriate use in emergency situations. The main components of the VA-ECMO circuit are depicted in Fig. 1. Multiple difficulties and complications may arise when VA-ECMO is used as an extension of CPR after intraoperative cardiac arrest in liver transplantation.
Timely Availability of ECMO A cardiac surgeon, a perfusion team, and an ECMO machine that is ready to be used need to be available. We recommend notifying the cardiac surgery team before the case if VA-ECMO is considered a rescue option for liver transplants to discuss the procedure and have emergency contact information available. The ECMO machine that is kept on standby does not
LIVER TRANSPLANTATION, Vol. 21, No. 3, 2015
need to be primed with fluid because this will take only a few minutes.
Access Large-bore cannulas need to be placed, most commonly into the femoral artery and vein, in order to allow sufficient blood flow. Access can be problematic during CPR, and cut-down is often a safer way to correctly identify the vessels. Approximately 25% to 35% of all liver transplant programs in the United States routinely place a femoral arterial catheter for liver transplantation.9 If access cannot be obtained rapidly, this catheter can be used to place the arterial catheter with the Seldinger technique. The size of the arterial cannula will frequently limit blood flow to the leg. This may particularly occur if high-dose vasopressor medications are required. If there is suspicion or evidence for hypoperfusion of the leg in which the arterial ECMO was placed, a distal perfusion cannula should be used that diverts a small amount of the total ECMO blood flow distally to the leg. Left ventricular distension can occur with VA-ECMO and will impede recovery of the myocardium; therefore, the left ventricle will need to be drained. In our case, we used a novel way to drain the left ventricle through the transdiaphragmatic incision. Frequent echocardiograms are useful to confirm adequate left ventricular decompression.
Coagulation Heparin needs to be given before the initiation of ECMO, and this may exacerbate coagulopathy and cause profound bleeding. A careful balance is required between treating bleeding and coagulopathy and the use of heparin to prevent clot formation in the ECMO circuit. After the initial bolus of heparin, further anticoagulation should probably be delayed until good hemostasis is achieved. In our case, the continued bleeding from the pericardial drainage and groin insertion sites prevented further administration of heparin, and this led to the removal of VA-ECMO earlier than initially anticipated.
Neurological Protection and Outcomes Cardiac arrest and CPR are associated with poor neurological outcomes in a large number of survivors. Therapeutic hypothermia after cardiac arrest can reduce mortality and improve neurological outcomes and is now recommended by many national and international CPR guidelines.10,11 However, bleeding complications caused by hypothermic coagulopathy may limit the ability to effectively cool a patient after cardiac arrest during liver transplantation. Furthermore, there are recent data that suggest that even mild hypothermia (36 C) may have a protective effect similar to that of hypothermia to 33 C.11 With the exception of local cooling by the placement of ice on the
LETTER FROM THE FRONTLINE 413
head, we neither cooled nor actively warmed our patient. The nadir temperature during the surgery was 33.8 C, and it was never higher than 36 C during the first 24 hours. Devastating neurological complications may occur and will become obvious within 24 to 72 hours after cardiac arrest when the patient does not regain consciousness. We recommend having a frank discussion about this possibility early on with the family. If any significant neurological recovery is unlikely, VA-ECMO should be withdrawn because it will be of no therapeutic use. VA-ECMO in this situation is an extension of CPR and should not be continued if a favorable outcome is unlikely, for example, in the event of a catastrophic neurological event.
Graft Protection Reperfusion cardiac arrest occurs at a time when the graft is exquisitely sensitive to further injury. During closed-chest CPR, the central venous pressure can increase dramatically12 and may lead to graft engorgement and dysfunction. Low blood perfusion may further impair graft perfusion and lead to graft failure. Once some degree of hemodynamic stability is achieved and before the operating room is left, the hepatic artery anastomosis should be completed to provide oxygenated blood to the graft. Graft function can be impaired if the venous cannula of the VA-ECMO occludes flow from the hepatic veins in the inferior vena cava. The position can be confirmed with transesophageal echocardiography. If liver function tests deteriorate, the cannula may need to be repositioned to allow adequate hepatic venous drainage.
Prognosis Preservation and rapid recovery of end-organ function are encouraging signs after the initiation of VAECMO. This includes adequate renal function and urine output, clearance of acid and improvement of lactic acidosis, and decreased vasopressor requirements. Among these parameters, urine output has been consistently found in many studies to be an excellent predictor of good outcomes.12-14 If organ perfusion cannot be restored rapidly, the prognosis is poor. Therefore, treatable causes for hypoperfusion, such as cannula size and position, hypovolemia, and bleeding, need to be addressed in a timely manner. Duration of VA-ECMO is a predictor of outcome. The prognosis is usually poor if there is no sufficient recovery of cardiac function after a few days of VAECMO support, and this is best assessed by transesophageal echocardiography. In summary, VA-ECMO may be a treatment option for refractory cardiac arrest during liver transplantation. It is associated with unique hazards and complications and requires the close cooperation of cardiac and liver transplant surgeons, anesthesiologists, and intensivists.
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Margaret Tejani, M.D.1 Soo Youn Yi, M.D.2 Kyle W. Eudailey, M.D.2 Isaac George, M.D.2 James V. Guarrera, M.D.2 Gebhard Wagener, M.D.1 Departments of 1Anesthesiology and 2Surgery College of Physicians and Surgeons Columbia University New York, NY
REFERENCES 1. Lee SH, Gwak MS, Choi SJ, Shin YH, Ko JS, Kim GS, et al. Intra-operative cardiac arrests during liver transplantation—a retrospective review of the first 15 years in Asian population. Clin Transplant 2013;27: E126-E136. 2. Matsusaki T, Hilmi IA, Planinsic RM, Humar A, Sakai T. Cardiac arrest during adult liver transplantation: a single institution’s experience with 1238 deceased donor transplants. Liver Transpl 2013;19:1262-1271. 3. Chen YS, Lin JW, Yu HY, Ko WJ, Jerng JS, Change WT, et al. Cardiopulmonary resuscitation with assisted extracorporeal life-support versus conventional cardiopulmonary resuscitation in adults with in-hospital cardiac arrest: an observational study and propensity analysis. Lancet 2008;372:554-561. 4. Cardarelli MG, Young AJ, Griffith B. Use of extracorporeal membrane oxygenation for adults in cardiac arrest (E-CPR): a meta-analysis of observational studies. ASAIO J 2009;55:581-586. 5. Bobrow BJ, Clark LL, Ewy GA, Chikani V, Sanders AB, Berg RA, et al. Minimally interrupted cardiac resuscitation by emergency medical services for out-of-hospital cardiac arrest. JAMA 2008;299:1158-1165.
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6. Eftestøl T, Sunde K, Steen PA. Effects of interrupting precordial compressions on the calculated probability of defibrillation success during out-of-hospital cardiac arrest. Circulation 2002;105:2270-2273. 7. Choi NK, Hwang S, Kim KW, Park GC, Yu YD, Jung SH, et al. Intensive pulmonary support using extracorporeal membrane oxygenation in adult patients undergoing liver transplantation. Hepatogastroenterology 2012;59:1189-1193. 8. Yoo CS, Shin YH, Ko JS, Gwak MS, Kim GS. Anesthetic management including extracorporeal membrane oxygenation therapy of liver transplant recipient with lifethreatening hypoxemia - a case report. Korean J Anesthesiol 2013;65:151-157. 9. Schumann R, Mandell MS, Mercaldo N, Michaels D, Robertson A, Banerjee A, et al. Anesthesia for liver transplantation in United States academic centers: intraoperative practice. J Clin Anesth 2013;25:542-550. 10. Hazinski MF, Nolan JP, Billi JE, B€ ottiger BW, Bossaert L, de Caen AR, et al. Part 1: Executive summary: 2010 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation 2010;122(suppl 2):S250-S275. 11. Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, et al. Targeted temperature management at 33 C versus 36 C after cardiac arrest. N Engl J Med 2013;369:2197-2206. 12. Delguercio LR, Coomaraswamy RP, State D. Cardiac output and other hemodynamic variables during external cardiac massage in man. N Engl J Med 1963;269:1398-1404. 13. Hsiao CC, Chang CH, Fan PC, Ho HT, Jeng CC, Kao KC, et al. Prognosis of patients with acute respiratory distress syndrome on extracorporeal membrane oxygenation: the impact of urine output on mortality. Ann Thorac Surg 2014;97:1939-1944. 14. Lin CY, Tsai FC, Tian YC, Jeng CC, Chen YC, Fang JT, Yang CW. Evaluation of outcome scoring systems for patients on extracorporeal membrane oxygenation. Ann Thorac Surg 2007;84:1256-1262.
LETTER FROM THE FRONTLINE
Extracorporeal Membrane Oxygenation as a Rescue Device for Postreperfusion Cardiac Arrest During Liver Transplantation Received October 16, 2014; accepted November 19, 2014.
TO THE EDITORS: Intraoperative cardiac arrest is a dreaded complication of liver transplantation with a poor outcome.1,2 The majority of cardiac arrests occur during the neohepatic phase, especially during reperfusion, and most are caused by either postreperfusion syndrome or pulmonary thromboembolic events.2 Almost 20% of patients with intraoperative cardiac arrest cannot be successfully resuscitated and do not regain a spontaneous rhythm and circulation. Of those who regain a spontaneous rhythm and circulation with cardiopulmonary resuscitation (CPR), more than 12% will not survive the surgery. The mortality of intraoperative cardiac arrest increases exponentially with the duration of CPR. If spontaneous rhythm and circulation are not restored rapidly, the prognosis is usually poor. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been used as an extension of CPR in many clinical scenarios with varying success. We describe a successful case of the use of VA-ECMO to treat postreperfusion cardiac arrest and discuss practical aspects of using VA-ECMO as rescue CPR during liver transplantation. CASE REPORT A 61-year-old man with hepatitis B cirrhosis and hepatocellular carcinoma underwent deceased donor liver transplantation. He had previously undergone transarterial chemoembolization of the hepatocellular carcinoma and esophageal banding for esophageal varices. His physiologic Model for End-Stage Liver Disease score was 8 (serum creatinine 5 0.66 mg/dL, total bilirubin 5 0.9 mg/dL, and international normalized ratio 5 1.2). He was well compensated and reported good exercise tolerance with no symptoms of cardiac disease. A transthoracic echocardiogram 3 months before surgery demonstrated a left ventricular ejection fraction of 60% to 65%, normal biventricular
systolic function, and no valvular pathologies. There was no evidence of wall motion abnormalities on a technetium-99m sestamibi pharmacologic stress test, which was also performed 3 months before surgery. A suitable standard criteria donor organ was identified (a 25-year-old woman who had a subarachnoid hemorrhage). The liver graft was procured and coldpreserved in a standard fashion without a perfusion circuit. The cold ischemia time of the graft was 5 hours 15 minutes, and the warm ischemia time was 47 minutes. The recipient was brought into the operating room, and after induction of general anesthesia, left radial and right femoral arterial catheters were placed along with a right internal jugular introducer with a pulmonary artery catheter without any complications. Initial intraoperative laboratory values were unremarkable. The dissection phase proceeded without complications and without the need for blood products. The patient tolerated clamping of the inferior vena cava and removal of the native liver with only low-dose vasopressor support (norepinephrine at 1 mg/minute and vasopressin at 1 U/hour). During the anhepatic phase, the patient remained hemodynamically stable and required slowly increasing doses of vasopressors with peak doses of norepinephrine of 6 mg/minute and vasopressin of 4 U/hour. The arterial blood gas analyses before reperfusion and at other time points are listed in Table 1. After complete caval clamping and removal of the native liver, the new graft was implanted with a bicaval end-to-end anastomosis and an end-to-end portal vein anastomosis. During this time, 2 g of magnesium and 1 g of calcium were administered. Caval and portal vein clamps were then removed. During the first 1 to 2 minutes after reperfusion of the transplanted liver, the blood pressure remained stable with initially decreased vasopressor requirements. However, within the first 4 minutes after reperfusion, the blood pressure decreased gradually, and this was
Potential conflict of interest: Nothing to report. Address reprint requests to Gebhard Wagener, M.D., Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, P&S Box 46 (PH-5), 630 West 168th Street, New York, NY 10032-3784. Telephone: 212-305-6494; FAX: 212-305-2182; E-mail: gw72@cumc. columbia.edu DOI 10.1002/lt.24056 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION. DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
C 2015 American Association for the Study of Liver Diseases. V
6.3 6.8 9.2 7.0 9.2 1.26 1.23 1.16 1.04 1.25 6.7 5.9 4.4 3.8 3.2 145 137 141 142 141
4.9 1.96 4.4 >170
6.2 1.36 4.1 138
12.6 9.8 8.5 1.18 1.03 1.20 3.3 3.3 4.0 138 139 138
15.8 11.2 20.5 25.8 27.0 29.6 217.6 24.0 3.6 2.2 32 39 34 28 28 7.31 7.06 7.39 7.57 7.56
>490 >490 >490 >490 347
29.5 7.9 26 7.66
271
18.1 26.7 32 7.36
164
27.1 24.3 24.0 3.2 0.4 20.7 >490 274 260 38 36 39 7.46 7.44 7.40
(mg/dL) (mmol/L) (mmol/L) (mmol/L) (mmol/L) (%) (mmol/L) (mmol/L) (mm Hg) (mm Hg) pH
Anesthesia start 100 0.8 100 1.0 100 1.9 Reperfusion 99 4.2 Start CPR 100 11.5 Start ECMO 100 >18.0 100 >18.0 100 10.0 100 5.9 >99.6 5:48 6:50 8:38 9:34 10:08 10:21 10:32 10:47 10:53 10:55 11:21 12:18 14:05 15:35
Time
Hemoglobin Ionized
calcium Na Lactate Concentration
Bicarbonate Base
of O2 of CO2
Excess
Partial Pressure Partial Pressure
TABLE 1. Blood Gas Analysis and Electrolytes During the Case
K O2
Saturation
Concentration
LIVER TRANSPLANTATION, Vol. 21, No. 3, 2015
LETTER FROM THE FRONTLINE 411
followed by increases in the pulmonary artery and central venous pressures. At this time, the patient remained in sinus rhythm with no apparent arrhythmias or other electrocardiogram changes. Despite escalating doses of phenylephrine and epinephrine, the hemodynamic parameters deteriorated, and the patient developed profound hypotension and bradycardia. CPR was initiated 24 minutes after reperfusion, initially externally and then internally through an incision of the subcardiac diaphragm. At this time, the patient developed ventricular fibrillation that did not respond to 5 attempts of internal defibrillation. During CPR, a total of 5 mg of intravenous epinephrine, 300 mg of amiodarone in 150-mg doses, 2 U of vasopressin, 100 mEq of sodium-bicarbonate in 50mEq doses, and 1 mg of intracardiac epinephrine were administered. After approximately 5 minutes of CPR, the cardiac perfusion team was called to initiate VA-ECMO. Throughout the cardiac arrest, internal CPR was very effective with evidence of good perfusion on the arterial blood pressure tracing. Therefore, no further attempts at defibrillation were made to avoid interruption of CPR. The patient remained in ventricular fibrillation until VA-ECMO was initiated. Ice was placed on the patient’s head as neuroprotection. At 21 minutes after the cardiac arrest, cardiac surgery completed the open cannulation of the right femoral vein (23F cannula) and left femoral artery (17F cannula). VA-ECMO was initiated after 30,000 U of heparin had been given. Approximately 10 minutes after the initiation of VAECMO, the cardiac rhythm spontaneously converted from ventricular fibrillation to a slow junctional rhythm. Pacing wires were placed into the myocardium through the incision in the diaphragm. We placed a transesophageal echocardiogram shortly after the initiation of VA-ECMO that showed an ejection fraction of 5% with moderate to severe left ventricular dilation. To decompress the dilated left ventricle, a cannula was placed into the left ventricular apex for drainage and connected to the extracorporeal membrane oxygenation (ECMO) circuit. An 8F catheter was inserted into the left superficial femoral artery cannulation and connected to the arterial side of the VA-ECMO circuit to maintain perfusion to the leg. Milrinone at 0.25 mg/kg/minute and 20 ppm of inhaled nitric oxide were initiated. At this time, the potassium level was 6.7 mEq, and it was treated with insulin and dextrose. As vasopressor requirements decreased, the liver, which initially became swollen and edematous when the central venous pressure was high, appeared less congested and viable. The decision was made to complete the liver transplant procedure with an end-toend hepatic artery anastomosis and choledochocholedochostomy. Hemostasis was adequate at the end of the operation, but the abdomen was packed because there was concern about bleeding with heparinization for VA-ECMO. After the left ventricular drain and pacing wires were secured and a Jackson-Pratt drain was
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placed in the pericardium, the abdomen was closed, and the patient was transferred to the intensive care unit. The total estimated blood loss was 4000 mL; he received 9 U of packed red blood cells, 5 U of fresh frozen plasma, and 130 mL of cryoprecipitate during the surgery. Throughout the cardiac arrest and while on VA-ECMO, the patient had good urine output of at least 1 mL/kg/hour. In the intensive care unit, he required multiple boluses of fluid and blood products to maintain VAECMO flow. A repeat transesophageal echocardiogram on postoperative day 1 demonstrated improvement of left and right ventricular function with an estimated left ventricular ejection fraction of 25% to 30%. Even though the liver function was satisfactory and the coagulation profile was only mildly abnormal, the patient continued to bleed from the left femoral arterial cannulation site and the Jackson-Pratt drain in the pericardium. At 48 hours after the initial surgery, he returned to the operating room; the VA-ECMO was successfully decannulated, and the abdominal packing was removed. The further postoperative course was unremarkable. His trachea was extubated 3 days after the transplant, and he was neurologically completely intact. He left the hospital 20 days after the initial surgery to go home and remained in good health with good graft function 3 months later. A transthoracic echocardiogram just before discharge found normal left and right ventricular function. DISCUSSION This case report demonstrates that VA-ECMO can be lifesaving in patients who experience cardiac arrest during liver transplantation. A large retrospective study found that intraoperative cardiac arrest during liver transplantation occurs in approximately 5.5% of cases. Intraoperative cardiac arrest was associated with a 29.4% intraoperative and 44.1% 30-day mortality. Approximately one-third of intraoperative cardiac arrests in this cohort were caused by reperfusion syndrome, one-third were caused by pulmonary thromboembolism, and only 7.4% were caused by hyperkalemia. The success of CPR decreases exponentially with the duration of CPR, even if occasional good outcomes have been reported after prolonged CPR. VA-ECMO is increasingly used as a rescue mode to maintain perfusion during CPR. It allows time to correct reversible causes of cardiac arrest or await spontaneous recovery of circulation or allows the placement of a longer term support system. It should be noted that the use of VA-ECMO in this situation provides precious time but does not necessarily correct the underlying cause of the cardiac arrest. The success of rescue VA-ECMO after cardiac arrest depends on the age, cause of cardiac arrest, and duration and effectiveness of CPR. A prospective study that compared patients with external CPR with patients who received VA-ECMO after 10 minutes of external CPR found a survival benefit with the use of
LIVER TRANSPLANTATION, March 2015
Figure. 1. Extracorporeal membrane oxygenation circuit: Blood flows from the venous cannula to the centrifugal pump to the oxygenator and then back through the arterial cannula to the patient.
VA-ECMO.3 Survival is poor in older patients and in cases in which VA-ECMO is initiated after more than 30 minutes of CPR.4 Postreperfusion cardiac arrest during liver transplantation may be well suited for rescue VA-ECMO and potentially better than external CPR. Direct access to the heart and open internal massage through the diaphragm can provide better perfusion while VA-ECMO circuit and cannulas are being prepared. Adequate blood pressure and perfusion during CPR will reduce the risk of potential sequelae of cardiac arrest and will improve the chances of recovery. Recent studies have indicated that frequent and prolonged interruptions of CPR for defibrillations, for example, may have deleterious effects.5,6 For this reason, no further attempts at defibrillation were made once the decision was made to proceed with VAECMO. Liver transplant teams may be familiar with venovenous ECMO because this has been used to enable liver transplantation in patients with severe hypoxia, for example, due to hepatopulmonary syndrome.7,8 VA-ECMO, however, is conceptually and technically different, and familiarity with this procedure may facilitate its appropriate use in emergency situations. The main components of the VA-ECMO circuit are depicted in Fig. 1. Multiple difficulties and complications may arise when VA-ECMO is used as an extension of CPR after intraoperative cardiac arrest in liver transplantation.
Timely Availability of ECMO A cardiac surgeon, a perfusion team, and an ECMO machine that is ready to be used need to be available. We recommend notifying the cardiac surgery team before the case if VA-ECMO is considered a rescue option for liver transplants to discuss the procedure and have emergency contact information available. The ECMO machine that is kept on standby does not
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need to be primed with fluid because this will take only a few minutes.
Access Large-bore cannulas need to be placed, most commonly into the femoral artery and vein, in order to allow sufficient blood flow. Access can be problematic during CPR, and cut-down is often a safer way to correctly identify the vessels. Approximately 25% to 35% of all liver transplant programs in the United States routinely place a femoral arterial catheter for liver transplantation.9 If access cannot be obtained rapidly, this catheter can be used to place the arterial catheter with the Seldinger technique. The size of the arterial cannula will frequently limit blood flow to the leg. This may particularly occur if high-dose vasopressor medications are required. If there is suspicion or evidence for hypoperfusion of the leg in which the arterial ECMO was placed, a distal perfusion cannula should be used that diverts a small amount of the total ECMO blood flow distally to the leg. Left ventricular distension can occur with VA-ECMO and will impede recovery of the myocardium; therefore, the left ventricle will need to be drained. In our case, we used a novel way to drain the left ventricle through the transdiaphragmatic incision. Frequent echocardiograms are useful to confirm adequate left ventricular decompression.
Coagulation Heparin needs to be given before the initiation of ECMO, and this may exacerbate coagulopathy and cause profound bleeding. A careful balance is required between treating bleeding and coagulopathy and the use of heparin to prevent clot formation in the ECMO circuit. After the initial bolus of heparin, further anticoagulation should probably be delayed until good hemostasis is achieved. In our case, the continued bleeding from the pericardial drainage and groin insertion sites prevented further administration of heparin, and this led to the removal of VA-ECMO earlier than initially anticipated.
Neurological Protection and Outcomes Cardiac arrest and CPR are associated with poor neurological outcomes in a large number of survivors. Therapeutic hypothermia after cardiac arrest can reduce mortality and improve neurological outcomes and is now recommended by many national and international CPR guidelines.10,11 However, bleeding complications caused by hypothermic coagulopathy may limit the ability to effectively cool a patient after cardiac arrest during liver transplantation. Furthermore, there are recent data that suggest that even mild hypothermia (36 C) may have a protective effect similar to that of hypothermia to 33 C.11 With the exception of local cooling by the placement of ice on the
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head, we neither cooled nor actively warmed our patient. The nadir temperature during the surgery was 33.8 C, and it was never higher than 36 C during the first 24 hours. Devastating neurological complications may occur and will become obvious within 24 to 72 hours after cardiac arrest when the patient does not regain consciousness. We recommend having a frank discussion about this possibility early on with the family. If any significant neurological recovery is unlikely, VA-ECMO should be withdrawn because it will be of no therapeutic use. VA-ECMO in this situation is an extension of CPR and should not be continued if a favorable outcome is unlikely, for example, in the event of a catastrophic neurological event.
Graft Protection Reperfusion cardiac arrest occurs at a time when the graft is exquisitely sensitive to further injury. During closed-chest CPR, the central venous pressure can increase dramatically12 and may lead to graft engorgement and dysfunction. Low blood perfusion may further impair graft perfusion and lead to graft failure. Once some degree of hemodynamic stability is achieved and before the operating room is left, the hepatic artery anastomosis should be completed to provide oxygenated blood to the graft. Graft function can be impaired if the venous cannula of the VA-ECMO occludes flow from the hepatic veins in the inferior vena cava. The position can be confirmed with transesophageal echocardiography. If liver function tests deteriorate, the cannula may need to be repositioned to allow adequate hepatic venous drainage.
Prognosis Preservation and rapid recovery of end-organ function are encouraging signs after the initiation of VAECMO. This includes adequate renal function and urine output, clearance of acid and improvement of lactic acidosis, and decreased vasopressor requirements. Among these parameters, urine output has been consistently found in many studies to be an excellent predictor of good outcomes.12-14 If organ perfusion cannot be restored rapidly, the prognosis is poor. Therefore, treatable causes for hypoperfusion, such as cannula size and position, hypovolemia, and bleeding, need to be addressed in a timely manner. Duration of VA-ECMO is a predictor of outcome. The prognosis is usually poor if there is no sufficient recovery of cardiac function after a few days of VAECMO support, and this is best assessed by transesophageal echocardiography. In summary, VA-ECMO may be a treatment option for refractory cardiac arrest during liver transplantation. It is associated with unique hazards and complications and requires the close cooperation of cardiac and liver transplant surgeons, anesthesiologists, and intensivists.
414 LETTER FROM THE FRONTLINE
Margaret Tejani, M.D.1 Soo Youn Yi, M.D.2 Kyle W. Eudailey, M.D.2 Isaac George, M.D.2 James V. Guarrera, M.D.2 Gebhard Wagener, M.D.1 Departments of 1Anesthesiology and 2Surgery College of Physicians and Surgeons Columbia University New York, NY
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