Anesthesia Following Heart Transplantation

1. Anesthesia Following Heart Transplantation R1 Minghui Hung Department of Anesthsiology, NTUH

2. Case History • The patient was a male aged 68 yr who had received heart transplant 6 years ago due to dilated cardiomyopathy with congestive heart failure • In general, his progress following surgery had been good with tolerant daily activity • Two episodes of graft rejection were noted at routine endomyocardial biopsy with adequate immunosuppresants control

3. Case History • Gross hematuria was noted this November. • Pelvic CT revealed an infiltrative tumor at right bladder wall and a hepatic tumor • Separate bladder TCC and HCC were confirmed by pathological results • Combined atypical hepatectomy and radical cystectomy with ileal conduit was planned, which was estimated to longer than 10 hours

4. Case History • preoperative immunosuppressive therapy triple-therapy oral prednisone, azathioprine, cyclosporin keep cyclosporin level at 80-160ng/dL

5. Case History • Laboratory studies WBC 5720 Anti-HCV negative Hb 10.4 HBsAg negative PLT 217K Anti-HBs negative AST 22 Anti-CMV negative ALT 11 T-Bil 0.2 Alb 3.97 ICG test: PT 12.4 15min 25.3% PTT 33.8 20min 13.3% AFP 2.64

6. Case History • U/A: • WBC 1-2 /HPF • chest X-ray

7. Case History • EKG

8. Case History • previous cardiac catheterization and endomyocardial biopsy • patent coronary vessels • no graft rejection • cardiac echography • Normal LV size with good contractility • AR, mild to moderate; Mild MR and TR • exercise test • severely decreased VO2max

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14. Postoperative course • Weaning and extubated on the next day • Transfer to general ward on day 3 with stable hemodynamics • Intravenous cyclosporin as immunosuppressant keep blood level 100-120 ng/dL • Antibiotics use, (Cefmetazone, gentamycin and metronidazole) for prophylaxis. • Geneally, uneventful postoperative course in the first week

15. 朱元璋一聯： 「雙手撇開生死路，一刀割斷是非根」 不亦快哉。

16. Heart transplantation (HTx) 1967, first human allograft cardiac transplant carried out by Christian Barnard “It is infinitely better to transplant a heart than bury it to be devoured by worms.” Time magazine

17. Orthotopic heart transplant

18. Heart transplantation (HTx) 86% 78% 65% Actuarial survial after triple-therapy in 1983

19. Major problem after HTx • Denervated donor heart • Immunocompromised on long-term immunosuppressive therapy (International Anesthesiology Clinics. 33(2)1-9, 1995 Spring)

20. Pathophysiology of the Denervated Heart • The recipient atrial remnant remains innervated, but no electrical impulses cross the suture line. • The donor atrium is responsible for the donor heart rate. • EKG: biphasic “P” waves. • No response to vagal stimulation, the resting heart rate is 90-120 bpm .

21. Pathophysiology of the Denervated Heart • Normal impulse formation and conductivity. • No response to vagal stimulation, the resting heart rate is 90-100 bpm . • No beat-to-beat variation in response to respiration.

22. Pathophysiology of the Denervated Heart • With normal Frank-Sterling law of the heart, the donor heart is “preload-dependent”. • In the first minutes of stress, stroke volume is increased instead of elevating heart rate. • Endogenous catecholamines was elevated after 5-6 minutes and heart rate increased.

23. Pathophysiology of the Denervated Heart • Alpha- and beta-adrenergic receptors remain intact but no clinical evidence of denervation hypersensitivity.

24. Pathophysiology of the Denervated Heart • Accelerated coronary atherosclerosis chronic rejection angiographic evidence: 10-20% at 1 year 50% by 5 years silent myocardial ischemia only diagnosed by EKG or angiography

25. Pathophysiology of the Denervated Heart • Arrhythmias Most common during the first 3-6 months • lack of vagal tone • increased level of circulating catecholamines • episodes of rejection • ischemia secondary to graft CAD Anti-arrhythmic agents or DC cardioversion should be carried out as normal, but negative inotropic effect should be considered.

26. Drugs in the Transplanted Heart • Diuretics, antihypertensives, antiarrhythmics, anticoagulants • Immunosuppressive drugs • Prednisone • Azathioprine • Cyclosporine • It has reported that incidence of malignancy following cardiac transplants is 6%.

27. Immunosuppressive agents Prednisone • insulin antagonism • sodium and fluid retention • Cushing’s syndrome • suppression of the hypothalamic-pituitary-adrenal axis • osteoporosis • gastric ulceration

28. Immunosuppressive agents Azathioprine • an antimetabolite • antagonize competitive neuromuscular blockade as a phosphodiesterase inhibitor • hepatic toxicity • bone marrow toxicity leading to leukopenia, thrombocytopenia, and anemia

29. Immunosuppressive agents Cyclosporine • suppressing both humoral and cell-mediated immunity • unprictable GI absorption, routine blood level measures needed • Nephrotoxicity • Avoid anesthetic drugs excreted mainly via the renal route. • Hypertension • Incidence of 75%, mainstay of treatment is calcium channel blockers and angiotensin-converting enzyme inhibitors.

30. Immunosuppressive agents Rejection and Infection • therapeutic dilemma of immuno-suppressing therapy • most common causes of mortality and morbidity • symptoms of rejection: tiredness, dyspnea, arrhythmia, transient ischemic attacks • ECG shows decrease in the QRS voltage • yearly routine postcardiac transplant follow-up, which includes echocardiography, cardiac catheterizaiton, coronary angiograms and endomyocardial biopsy

31. Anesthesia for the Patient with a Denervated Heart Preoperative Assessment • CBC, urea, creatinine, and electrolyte level, liver function test, pulmonary function test, chest X-ray, EKG • In particular, looking for any features of coronary atherosclerosis or graft rejection • Check pacemaker preoperatively if the patient is fitted with one • Review drug history • Steroid supplements and proper prophylactic antibiotics • Coagulation status

32. Anesthesia for the Patient with a Denervated Heart Monitoring • Standard monitoring for any safe anesthetic • Carefully weighed against the potential risk of infection for invasive monitoring • Fully aseptic techniques

33. Anesthesia for the Patient with a Denervated Heart Intraoperative management • avoid dehydration, volume loss, and peripheral vasodilation, and to maintain preload • in general, geneal anesthesia is preferred with intravenous induction • regional anesthesia is problematic and require adequate preloading to avoid exaggerated hypotension

34. Anesthesia for the Patient with a Denervated Heart Intraoperative management • Bradycardia and hypotension • Isoprenaline (Isuprel®), a direct beta-adrenergic agonist, increased heart rate, cardiac output, and systolic blood pressure, and a reduced total peripheral resistance and diastolic blood pressure • Ephedrine, direct alpha- and beta-adrenergic agonist, increased systolic and diastolic blood pressure, increased pulse pressure and pulse rate, increased venous return and cardiac output

35. Anesthesia for the Patient with a Denervated Heart Postoperative Care • routine chest physical therapy for possible pulmonary infection • fluid balance for fluid overload or reduced renal perfusion • the polypeptide sequence from amino acids 99-126 of the natriuretic factor (Urodilatin®) have shown to have profound effects on renal function • early postoperative mobilization minimizes the risk of deep venous thrombosis and pulmonary embolism • continue all drug therapy, including immunosuppresants

36. Thank You! Happy New Year!