Anesthesia for Organ Transplantation

1. Anesthesia for Organ Transplantation By Anselmo Serna Greg McMichael

3. All vital organs: Heart, Lung, Liver and Kidney, can be supported by technology or replaced by transplantation. Except the brain, it is the only organ that cannot be functionally supported or replaced.

4. Transplantation • Expertise in the anesthetic management of the organ recipient as well as the organ donor has a major impact on the quality of the graft organ, the viability of the transplanted graft, and as a result the long term survival of the transplant recipient. • Training in organ transplantation anesthesia will result in better initial management of these patients, innovative therapeutic interventions in the future, and improved outcome among transplanted patients.

6. How much does an organ transplant cost? • Bone Marrow - $250,000 • Heart - $300,000 • Heart/Lung - $300,000 to $350,000 • Isolated Small Bowel Transplant - $350,000 • Kidney - $75,000 to $100,000 • Kidney/Pancreas - $150,000 • Liver - $250,000 • Lung - $200,000 to $250,000 • Pancreas - $100,000

7. Most Transplant Patients... • Are in surgery approximately 3-7 hours • Spend 1 day on the ventilator • Spend 1-2 days in the intensive care unit • Are discharged 7-12 days after their surgery

8. Reasons not to transplant • Advanced heart, kidney or liver disease • HIV infection • Cancer • Hepatitis B • Hepatits C with proven cirrhosis by liver biopsy • Current substance abuse: tobacco, alcohol and illicit drugs • Body weight less than 80% or greater than 120% of predicted • Inability to carry out the responsibilities necessary to maintain a healthy lifestyle and remain compliant with all medications

9. Candidacy for Transplantation • The evaluation consists of: • Bloodwork • Urine tests • Radiologic tests • Heart and Lung tests • Tests for osteoporosis • Dental consult • Interview with a social worker • Gastrointestinal consult for patients with scleroderma or a history of reflux • Females: pap smear and mammogram

10. Transplantation • Transplantation is a multidisciplinary field that encompasses a wide range of basic and clinical medical and biological sciences. • The science of transplantation constitutes a biochemical, pathophysiologic, and clinical continuum from organ donor to organ recipient. • A better understanding of the biochemical, pathophysiologic and clinical problems encountered in the management of the organ transplant recipient and organ donor can be achieved through a broad based multidisciplinary approach.

11. Liver Transplants • Liver transplants are performed in many centers across the country. The healthy liver is obtained from a donor who has recently died but has not suffered liver injury. The healthy liver is transported in a cooled saline solution that preserves the organ for up to 8 hours, thus permitting the necessary analysis to determine blood and tissue donor-recipient matching. The diseased liver is removed through an incision made in the upper abdomen. The new liver is put in place and attached to the patient's blood vessels and bile ducts. The operation can take up to 12 hours to complete and requires large volumes of blood transfusions.

16. Anesthesia Techniques • There is no particular “liver anesthetic.” It is, however, recommended that a uniform approach be used initially. For induction and intubation, fentanyl, sodium pentothal/etomidate, low dose non-depolarizing muscle relaxant, and succinylcholine will be used. Anesthesia will be maintained with fentanyl, benzodiazepines, non-depolarizing muscle relaxant, and isoflurane in air/oxygen. 5 cm PEEP will be used to reduce the risk of air emboli and to prevent atelectasis. • Use caution in administering N2O as its use may lead to bowel distention and can compromise surgical exposure.

17. Preparation • Monitors: central line for fluid replacement; CVP for monitoring fluid status; a-line for beat-to-beat monitoring of heart rate/pressure and multiple blood draws; foley catheter for urine output • 2 large-bore peripheral IVs (16g or greater) for blood replacement • Rapid transfusers • Fluid and body warmers

18. Blood and Blood Products • Typical transfusion requirements consists of: • 15-30 units of PRBCs • 15-25 units of platelets • 15-30 units of FFP • 10-20 units of cryoprecipitate • Cell saver also helpful in reducing reliance on donor RBC transfusions

19. Intraoperatively • Procedure lasts 4-18 hours and is divided into three phases: • Dissection • Anhepatic • Revascularization

20. Dissection • Through a wide subcostal incision the liver is dissected so that it remains attached only by the inferior venacava, portal vein, hepatic artery and common bile duct. • Previous abdominal procedures greatly prolong the duration of this phase

21. Anhepatic • Once the liver is freed the inferior venacava is clamped above and below the liver as well as the hepatic artery and portal vein • Liver is then completely excised and venovenous bypass may be employed at this time • Donor liver is then anastomosed to recipient patient

22. Venovenous Bypass • When inferior venacava and portal vein are clamped marked decreases in cardiac output and hypotension are typically encountered. For patients identified at increased risk for venacava clamping, venovenous bypass is used. • Venovenous bypass can help minimize severe hypotension, intestinal ischemia, build up of acid metabolites and postoperative renal dysfunction

23. Revascularization • Following completion of venous anastemosis the venous clamps are removed and the circulation to the new liver is completed • Lastly the common bile duct of the donor is then connected to the recipient

24. Management of liver reperfusion Take steps to bring potassium to appropriate level (< 4.0) Discuss at least 4 ways to reduce potassium Replace calcium to ensure normal (> 5.0) Correct lactic acidosis (pH normal) Appropriate volume infusion to maintain euvolemia Hemoglobin appropriate (9 – 10 for most patients) Calcium 100mg/cc attached to iv ready for administration. Epinephrine 10 mcg/cc attached to iv ready for administration Epinephrine 20 mcg/cc on baxter pump ready for infusion Communication with surgeon – OK for reperfusion

25. Heart Transplant

26. Indications for Transplant • Idiopathic or ischemic cardiomyopathy • Viral cardiomyopathy • Inoperable coronary artery disease with congestive heart failure • LV ejection fraction less than 20% • Amyloidosis • Severe congenital heart disease without other surgical options • Life-threatening abnormal heart rhythms that do not respond to other therapy • Inoperable heart valve disease with congestive heart failure

27. Most Common Causes of End Stage Cardiac Failure • Coronary artery disease • Cardiomyopathy • 90 percent of heart transplants • Congenital and valvular heart disease • A small percentage of end stage heart failure

28. Pathophysiology • End stage Cardiomyopathy: both systolic and diastolic dysfunction • Decreased SV • Decreased CO • Decreased O2 transport and exercise capacity • Multiple comorbitities usually including DM, HTN, PVD, renal dysfunction

29. Compensatory Mechanisms • Renal retention of NA and H2O • Increased preload • SNS stimulation • Increased HR and contractility • Increased endogenous catecholamines • Increased contractility • Decreased venous capitance • Increased preload

30. Failed Compensatory Mechanisms • Increased Preload • Dilated LV, Mitral Regurg, pulmonary edema • Increased afterload • Hypertrophy • Increased contractility from increased endogenous catecholamines • Leading to a decrease in the sensitivity of the heart and the vasculature to these agents via a decrease in receptors (down-regulation) • Decrease in the myocardial norepinephrine stores • Increased afterload • Decreased CO • Renal retention of Na and H2O • pulmonary vascular congestion and edema, ascites

31. Treatment • Diuretics • May result in hypokalemia and hypomagnesemia and hypovolemia • Slow incremental B-Blockade (metoprolol) • Can improve hemodynamics and improve exercise tolerance in pts awaiting transplant • Inotropes (amiodarone, milrinone, enoximone) • Toxic side effects and increased mortality • Anticoagulants • Prevent pulmonary and systemic embolization • Digitalis • Weak inotrope with toxic side effects • Vasodilators (nitrates, hydralazine, ACE inhibitors) • Decrease the impedance to LV emptying • Intraaortic balloon counterpulsation • Vascular complications and immobilizes pts • VADs • Improves myocyte contractile properties and increases B-adrenergic responsiveness

32. Donor Caveats • Donors can exhibit major hemodynamic and metabolic changes and thus should be constantly monitored with inotropic and vasopressor support • Hypovolemia • Myocardial injury • Catecholamine storm • Inadequate sympathetic tone due to brainstem infarct

33. Donor Cardiectomy • Median sternotomy and heparinization • Cannulation of the ascending aorta for cold hyperkalemic cardioplegia • SVC ligated, IVC transected to decompress the heart • Topically cooled with iced saline

34. Donor Cardiectomy (cont’d) • After arrest, pulmonary veins are severed • SVC transected • Ascending aorta divided just proximal to the innominate artery • PA transected at its bifurcation • Heart is then transported via ice chest • Upper time limit for ex vivo storage of human hearts is approximately 6 hours

35. Transplantation: Preop • Rapid H&P of recipient due to time constraints • Equipment and drugs similar to those usually used for routine cases requiring CPB should be prepared • Placement of invasive monitoring • PA catheter, arterial line, TEE • CO, PVR, CVP • Aspiration Precautions • Blood products: CMV negative • Aseptic technique with broad spectrum antibiotic prophylaxis

36. Transplantation: Intraop • Induction of Anesthesia balances risk of aspiration of gastric contents with hemodynamic changes • High dose narcotic with muscle relaxant and benzodiazepines • RSI: etomidate, succinylcholine, moderate dose fentanyl • Most patients called in for transplantation have not fasted and should be considered to have a full stomach • Induction should be preformed in the presence of the surgeon, scrub nurse and perfusionist in anticipation for cardiovascular collapse • Anticipate altered drug responses due to low CO and slow circulation time as well as decreased volume of distribution • Preinduction administration of inotropic agents or pressors optimizes circulation and minimizes transit time of subsequently administered anesthetics

37. Transplantation: Intraop (cont’d) • Maintenance of Anesthesia • High dose narcotic, benzodiazepines, muscle relaxant, O2, low dose volatile agent • High dose narcotic can cause ventricular arrhythmias • Volatile agents can cause pre-CPB hypotension • OG and foley placed • The PA should be withdrawn from the right heart prior to completion of bicaval cannulation

38. Cardiopulmonary Bypass • Hypothermia 28-30* C • Furosemide to promote UO • Hemoconcentration for expanded blood volume • Anastamosis: LA, RA, PA, aorta • Glucocorticoid (methylprednisone 500 mg) is administered as the last anastamosis is being completed prior to the release of the aortic cross clamp to attenuate any hyperacute immune reaction. • TEE used to monitor whether the cardiac chambers are adequately de-aired and can diagnose atrial torsion, RV outflow obstruction, and decreased R or L ventricular systolic function • Longer rewarming period • During reperfusion, an infusion of an inotrope is begun for both inotropy and chronotropy • Donor heart should be paced if bradycardic despite inotrope infusion also the possibility of IABP, ECMO, or LVAD • RV dysfunction from elevated PVR is the most common cause of perioperative heart failure, use of pulmonary vasodilators: milrinone, nitric oxide, sodium nitroprusside • Arrhythmias: slow junctional or AV nodal, V fib

42. Transplantation: Postop • Low CO after transplant may be due to: hypovolemia, inadequate adrenergic stimulation, myocardial injury during harvesting, acute rejection, tamponade, sepsis. • Systemic hypertension may be due to pain, adequate analgesia is provided before vasodilators • Atrial and ventricular tachyarrythmias are common in the immediate postop period, once rejection has been ruled out, antiarrythmics are used for conversion (except those with indirect acting mechanisms or negative inotropes) • Many patients require pacing in the immediate postop period and 10-25% require permanent pacing • Renal function often improves following transplantation, but immunosuppressants may again impair renal function • Bacterial pneumonia is very common in the early postop period and opportunistic viral and fungal infections after the first several weeks

43. Pharmacological Agents After Transplant • The transplanted heart has no autonomic innervation • Agents that act indirectly via the sympathetic or parasympathetic system (atropine, ephedrine) will be ineffective. • Drugs with a direct/indirect effect will only have their direct effect seen. • Drugs of choice are direct effect – isoproterenol, epinephrine, etc. • May require pacing

44. Adenosine Atropine Digoxin Edrophonium Ephedrine Norepinephrine Pancuronium Phenylephrine Nifedipine Supersensitivity No vagolytic effect No vagotonic effect No vagotonic effect Less cardiostimulation Unmasked beta effects No vagolytic effect Diminished sensitivity Nodal conduction not depressed Cardioactive Drug Responses in the Denervated Heart

45. Anesthesia for Patients With Previous Transplant • Transplanted patients require anesthetic for surgical procedures that may or may not be cardiac related • Preoperative evaluation includes extensive reevaluation of cardiac function • Systolic function is usually normal but a significant number of patients develop diastolic dysfunction, manifested as exercise intolerance • Abnormalities in isovolumic relaxation time correspond with varying degrees of rejection • Increased peak inflow velocity and mitral deceleration are indicators of restrictive filling • Rejection causes inflammatory infiltrate that causes edema • The presence of rejection increases perioperative morbidity and the incidence of asymptomatic arrhythmias • Complication related to immunosuppression should be considered, including opportunistic infections • Immunosuppressants side effects include nephrotoxity as well as neurotoxicity and cyclosporin is associated with cholelithiasis, increasing the incidence of cholecystectomy in these patients • Repeated biopsies for routine transplant management may cause injury to the tricuspid valve with severe tricuspid regurg • Often requires tricuspid valve replacement

46. Anesthesia for Patients With Previous Transplant • Choice of anesthetic depends on the type of surgery and condition of the patient • Regional anesthesia can be used cautiously, with the knowledge that these patients cannot mount the usual response to vasodilation and hypotension • Cardiovascular monitoring is dependent on the nature of the planned surgery. Invasive monitoring is not necessary for minor procedures. Intraoperative echocardiography is important in managing volume status. • The ECG may have a double P wave, reflecting atrial activity in the native atrial cuff and the transplanted atrium • Cardiac output of the transplanted heart is preload dependent and rely on changes in stroke volume. Ephedrine or isoproterenol should be readily available to treat bradycardia as atropine will not have an effect. • Patients with prior heart transplantation have undergone successful pregnancies

47. Lung Transplantation

48. Overview • Indications: end-stage parenchymal disease or pulomonary hypertension. Candidates are functionally incapacitate by dyspnea and have a poor prognosis. • Criteria varies according to the primary disease process

50. Single vs. Double Lung Transplant • Single-lung transplantation may be performed for selected patients with chronic obstructive pulmonary disease, whereas double-lung transplantation is typically performed for patients with cystic fibrosis, bullous emphysema, or vascular diseases. Younger patients are more likely to receive bilateral lung transplants.