Heart Transplants_ An Anesthesiologist's Perspective by wuyunqing

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									Anesthesia for Adult Heart

  Resident Seminar, Nov 2010
       Ahmed F. Hegazy
Canadian Data & Survival Rates
Indications for Heart Tx
Recipient Contraindications
Medical Urgency Status Codes
Donor Criteria
Anesthesia for Organ Procurement
Surgical Technique
Anesthetic Considerations for
Post-bypass period.
•   1967- first human to
    human heart transplant,
    South Africa

•   1968- first Canadian
    heart transplant in

•   1978- Cyclosporine first
    tested in humans

•   1983- first Canadian
    heart lung transplant (in
                N Engl J Med. 2006 Jul 20;355(3):231-5
Taking heart--cardiac transplantation past, present, & future. Hunt SA.
Heart Tx: Canadian
From 1999 to 2008:

•   1,643 heart transplants including 55 re-transplants

•   ≈ 165 heart transplants per year

•   Hospitals performing heart transplants:
    11 (BC, AB, ON, QC & NS).

•   deaths on heart transplant waiting list
    (from 1999 to 2008): 269
Heart Tx: in London…

•   Since 1981, 568 heart transplants performed

•   On average around 10 to 16 heart transplants per
     Survival after Heart Tx
•Highest mortality in
the first 6 months
•Average 1 year
survival is 86%
•Beyond 1 year,
mortality nearly
constant at around
4% per year
 Indications for Heart Tx
End-stage heart disease refractory to medical or
 surgical therapy

 Ischemic Cardiomyopathy

 Nonischemic Cardiomyopathy (dilated,
 hypertrophic, restrictive)

 Valvular Heart Disease


 Adult Congenital Heart Diseases

 Miscellaneous Conditions
    Pathophysiology of
•   LV systolic failure (    stroke volume)

•   LV diastolic failure (   LV compliance)

•   Eventually   back pressure   pulmonary
    venous pressures pulmonary hypertension

•   Renin-Angiotensin-Aldosterone activation    salt
    and water retention

•   Chronically elevated catecholamine levels   β1
    receptor down regulation

•   Severe irreversible pulmonary hypertension
    (PVR > 6 Wood units/m2 and high transpulmonary
    gradient > 15mmHg)

•   Active infection, active or recent malignancy (< 2
    years), HIV positive serology

•   Severe irreversible hepatic, renal or pulmonary
    disease or any other major debilitating comorbid

•   Severe mental or psychiatric illness, drug abuse.


•   Advanced age > 65

•   Brittle diabetes with end-organ damage

•   Morbid obesity (BMI > 35)
Urgency Status Codes
Trillium Gift of Life Network status criteria
  (a very simplified version):

•   Status 4: in ICU on mechanical ventilation and

•   Status 3: in ICU on inotropes

•   Status 2: hospitalized

•   Status 1: at home
    Donor Selection
•   Confirmed NDD with age <70

•   ABO blood group

•   Weight (or BMI) ratio

•   Organ viability (assessed by ECG,
    echocardiography and coronary angiography)
Anesthesia for Organ Procurement
Your only ASA 6 E patient!
 …but no billing code for that 

•   Maintain volume status and systemic arterial and
    central venous pressures.
    Volume (some have DI) ± blood inotropes /
    pressors steroids, vasopressin, thyroxine

•   Maintain PaO2 >100mmHg.
    FiO2 of 1 if no lung harvest
    FiO2 of <50 % if lung harvest

•   Non depolarizing muscle relaxant to prevent spinal-
    reflex mediated muscle movement
Anesthesia for Organ Procurement
•   Spinal mediated hypertension and tachycardia (not
    due to pain perception).

•   Full heparinization after initial dissection

•   Perfusion-sensitive organs (kidneys and liver) first
    then heart.

•   Sternotomy, heart excision (after cardioplegia)
    plastic bag with ice-cold saline. Transported in ice-
    filled cooler.

•   Donor heart ischemic time <4 hours.
Surgical Techniques

•   Examine donor heart for PFO.

•   Orthotopic:
    Recipient heart excised (98% of cases)
    1. Biatrial technique
    2. Bicaval technique

•   Heterotropic:
    Donor heart placed in right anterior thorax.
    Creating two parallel circulations.
Surgical Techniques
•   Orthotopic:

    1. Biatrial technique.

    Originally described technique

    Preserved portions of native right & left atria.

    Anastomose donor to recipient atria (left then
    right), then aorta (to allow coronary perfusion) then
    pulmonary artery.
           N Engl J Med. 2006 Jul 20;355(3):231-5
Taking heart--cardiac transplantation past, present, & future.
Surgical Techniques
•   Orthotopic:

    2. Bicaval technique.

    Remove native right atrium and keep left atrium

    Anastomose donor to native left atria then both
    venae cavae (bicaval) then aorta then pulmonary

    Preserves right atrial geometry and hence
    decreases TR.
           N Engl J Med. 2006 Jul 20;355(3):231-5
Taking heart--cardiac transplantation past, present, & future.
Surgical Techniques
•   Heterotropic:

    Donor heart placed in right anterior thorax.

    Creating two parallel circulations.

    Anastomose atria to atria, then aorta to aorta, then
    pulmonary artery to pulmonary artery via an
    artificial conduit.

    Native RV supports right circulation and donor RV
    supports left circulation

    Can be done if severe pulm. HTN or small donor
Ann Thorac Surg 1998; 65: 857-858
    Anesthesia for the recipient
•   Preoperative evaluation: limited time, short notice

    History and Physical Exam:

    1. Etiology of heart disease & current status
    2. Concomitant organ dysfunction
    3. Previous cardiac surgery (repeat sternotomy)
    4. Preoperative meds
    5. If from ICU: preoperative monitoring and
    circulatory support
    6. might not be NPO
    “I stopped eating as soon as I got the call”
    Anesthesia for the recipient

•   Preoperative evaluation: limited time, short notice


    1. last echo and/or cardiac work-up: LV / RV
    functions, pulm. HTN, valves..
    2. grouped and crossed and blood available?
    3. routine: CBC, lytes, BUN Creatinine, liver
    functions, CXR, Coags, ± PFTs…
    4. viral screen (CMV, HIV, Hep B & C, EBV)
Anesthesia for the recipient

Timing of induction:
communication with transplant team is crucial.

Induction of anesthesia should be a good 1 ½ to 2
hours before the donor heart arrives (while
heart is en-route).

Patient Considerations: end-stage heart failure.

Premedication: none to minimal
 Anesthesia for the recipient
 Aseptic technique is imperative
 1. Standard CAS monitors, 5-lead ECG, awake art.
 2. Large bore IV, rapid infusor available
 2. Rt IJ vein okay for access.
    PA catheter useful to gauge RV afterload
    coming off bypass.
    Don’t forget to pull it out to the SVC before they
    excise the heart!
 3. TEE
Anesthesia for the recipient
Anesthetic Induction:
1. Hemodynamic considerations: hypokinetic,
dilated, non-compliant ventricles. Preload
dependent & afterload sensitive.
Maintain perioperative cardiac supports and stay
on top of things!

2. Aspiration precautions.

3. “Opioid based anesthetic” with benzo.
supplementation, muscle relaxation and very little

4. Antifibrinolytic.
    Anesthesia for the recipient
•   Post bypass period:

    Evacuation of air from the heart with TEE
    guidance. Cross clamp may be removed in
    Trendlenberg position.

    Regular bypass checklist: ABGs, temp, lytes… plus
    1. RV dysfunction
    2. Coagulation
    3. LV dysfunction
    4. Renal Dysfunction
    Anesthesia for the recipient
•   Post bypass period:

    1. RV dysfunction:
    Be prompt in treating it, it accounts for nearly 20% of
    early post transplant deaths.

    i) avoid hypoxia, hypercarbia, acidosis, hypothermia..
    ii) always coming off bypass, have ready: milrinone,
    isoproterenol (plus your regular epi)
    iv) pace to a HR of 90 to 100 if necessary (the RV hates
    iii) inhaled nitric oxide
    iv) others: dobtutamine, PGI2 (flolan), IABP…
    Anesthesia for the recipient
•   Post bypass period:

    2. Coagulation:

    Risk factors: preoperative anticoagulation, preop.
    liver dysfunction, long CPB time, hypothermia.

    Blood should be leucocyte reduced.
    FFP, platelets, cryoprecipitate, DDAVP, Factor
    Anesthesia for the recipient
•   Post bypass period:

    3. LV dysfunction:

    Risk factors: prolonged donor ischemia time,
    inadequate myocardial protection, intracoronary
    Treat with pharmacologic ± mechanical support.

    4. Renal dysfunction:
    Risk factors: preoperative dysfunction,
    perioperative hypotension, CPB, cyclosporin.
Anesthetic Considerations
    for the Post Heart
   Transplant Patient

•   Physiology and Pharmacology

•   Preoperative evaluation

•   Anesthetic Management:
    1. Immunosuppressed
    2. Monitoring
    3. Techniques of Anesthesia
    4. Blood Transfusion
Physiology & Pharmacology

•   Denervated heart:
    1. No parasympathetic innervation
    2. No sympathetic innervation
    3. Intact humoral response to circulating catechols
    4. Can develop silent ischemia

•   Resting heart rate usually around 90 to 110.

•   Sinus bradyarrhythmias in 20% of cases.
Physiology & Pharmacology

•   Indirect acting drugs: inneffective

•   No reflex tachy or brady in response to changes in

•   β-adrenergic response to direct acting
    catecholamines is increased.
Physiology & Pharmacology
    Drug             Action          Heart rate Blood Pressure
   Atropine          indirect            -            -
 Pancuronium         indirect            -            -
   Fentanyl          indirect            -            -
  Ephedrine      indirect & direct     -/           -/
Phenylephrine         direct             -
 Isoproterenol        direct                         -/
Norepinephrine        direct
 Neostigmine         indirect          -/             -
  Verapamil           direct
Physiology & Pharmacology

•   Intrinsic cardiac mechanisms preserved i.e.
    preserved Frank-Starling volume pressure

•   In denervated heart, cardiac output can be only
    by stroke volume (as HR not rapidly responsive).
    Therefore CO is critically preload dependent.
Physiology & Pharmacology

•   With time, functional reinnervation can be

•   Possibly starting after 1 year.

•   Complete reinnervation reported after 15 years.
Preoperative evaluation: Sx &
•   Nature of surgical procedure: may be a sequele to
    the heart Tx and the immunosuppression.

•   Thorough medical history emphasizing:
    1. Transplant follow-up.
    2. Exercise tolerance
    3. Angina ? (absence doesn’t exclude CAD)
    4. Hypertension, diabetes, epilepsy
    5. Renal impairment
    6. Permanent pacemaker
    7. Other complications post-heart transplant.
Preoperative evaluation: Hx

 8. Complications post OHT:

 (i) Rejection

 (ii) Infection

 (iii) Cardiac allograft vasculopathy (CAV)

 (iv) Malignancies
Preoperative evaluation: Hx
    (i) Rejection:

•   40% in first year, then incidence

•   cell mediated (lymphocytic infiltration) or humoral
    (antibody mediated)

•   Endomyocardial biopsies (EMB) done routinely
    through Rt IJ vein for early detection.

•   Rejection maybe asymptomatic or presenting with
    CHF, arryhthmias, fever.
Preoperative evaluation: Hx
    (i) Rejection:

•   Timeline:
    1. Hyperacute: occuring within 24 hrs postop.
    2. Acute: over 4 to 6 weeks
    3. Chronic: over months to years.

•   Treatment:
    1. increased immunosuppression (e.g. steroids… )
    2. IVIG / plasmapheresis
    3. mechanical support until heart recovers.
Preoperative evaluation: Hx

    (ii) Infections:

•   CMV: prophylactic valganciclovir or ganciclovir

•   Fungal infections: Candida and Aspergillus

•   Line infections, wound infections and pneumonias
    should be treated aggressively

•   Infections account for up to 20% of deaths in the
    early postoperative period.
Preoperative evaluation: Hx

(iii) Cardiac Allograft Vasculopathy (CAV):

•   Leading cause of death beyond 1 year.

•   Aetiology: immunological and non immunological
    factors (e.g. hypertension and hyperlipidemia)

•   Often diffuse and involving distal coronaries

•   Presentation: asymptomatic, silent MI, progressive
    CHF, sudden death
Preoperative evaluation: Hx

(iii) Cardiac Allograft Vasculopathy (CAV):

•   Diagnosis: intravascular ultrasound (most
    sensitive) , coronary angiogram (may be not
    adequately imaged)

•   Treatment:
    1. sirolimus, diltiazem, statins
    2. PCI vs CABG, success limited
    3. retransplantation?
Preoperative evaluation: Meds


•   Perioperative immunosuppressants:
    1. Leucocyte depleting agents
    2. IL-2 receptor blockers

•   Maintenance immunosuppressants:
    1. Calcineurin inhibitors
    2. Antiproliferative agent (cell cycle inhibitor)
    3. Steroids: prednisolone
Preoperative evaluation: Meds

•   Perioperative immunosuppressants:

    1. Leucocyte depleting agents: Antithymocyte
    globulin & OKT 3.
    Opsonize & lyse T cells. Given IV only.
    Side effects: fever, chills, hypotension,
    anaphylaxis, leucopenia and infection.

    2. IL-2 receptor blockers: basiliximab, dacluzimab
Preoperative evaluation: Meds
•   Maintenance immunosuppressants:

    1. Calcineurin inhibitors: cyclosporine & tacrolimus.
    Suppress IL-2 production by T-cells.
    Side effects: nephrotoxic, neurotoxic: tremors,
    parasthesias, hypertension, diabetes, gingival

    2. Antiproliferative agent (cell cycle inhibitor):
    azathioprine & mycophenolate mofetil (MMF).
    Inhibit lymphocyte proliferation.
    Side effect: bone marrow suppression.
Preoperative evaluation: Meds

•   Maintenance immunosuppressants:

    3. Steroids: prenisolone. Inhibit T-cell activation,
    cytokine production & leucocyte chemotaxis.
    Very effective but large side-effect profile so
    tapered off after 6 to 12 months post OHT.
Preoperative evaluation

  Examination: Airway may be difficult due to
   lymphoproliferative disease, DM, or soft tissue
   enlargement due to steroids.

    1) ECG: more than one P-wave (only if biatrial
    2) routine bloods CBC, lytes, kidney and liver
    functions, coags and CXR
    3) latest coronary angio, EMB?
Anesthetic considerations

  •   Anesthetic Management:
      1. Immunosuppressed
      2. Monitoring
      3. Techniques of Anesthesia
      4. Blood Transfusion
Anesthetic considerations:
  •   Strict aseptic techniques

  •   Get rid of lines / indwelling catheters as early as

  •   Antibiotic prophylaxis if bactremia producing
      procedure and patient has valvulopathy.

  •   NSAIDs? Try to avoid with other potential

  •   Suplemental “stress” dose steroids.
Anesthetic considerations: Monitoring

  •   Standard CAS monitors

  •   ± art. line, central line… as situation mandates…
      with strict asepsis

  •   Peripheral nerve stimulator to monitor muscle
      Cyclosporine prolongs non-depolarizers
      Azathioprine decreases non-depolarizers
Anesthetic considerations: Techniques
  Both general and regional have been used safely.

  Always maintain ventricular filling pressures.

  •   General Anesthesia:
      Difficult to assess anesthetic depth
      Avoid hyperventilation as calcineurin inhibitors
      lower the seizure threshold.

  •   Regional:
      Check for coagulopathy.
      Ensure ventricular filling pressures.
      Treat hypotension with direct acting meds.
Anesthetic considerations: Transfusion

  •   CMV negative patients should receive CMV
      negative blood.

  •   Use irradiated, leuco-depleted blood to avoid
      immunomodulation and graft versus host disease.
Take homes!
Review: Anesthesia for OHT
•   Assess the recipient as soon as you hear about
    him, timing for induction is crucial.

•   Recipients have end stage heart disease and are
    preload dependent and afterload sensitive.

•   The status of your donor heart will affect your

•   Coming off bypass your issues are
    1. right ventricular support (have milrinone,
    isopproterenol, epi and a pacer box ready)
    2. bleeding
Review: Anesthesia post
  OHT hearts are denervated so use direct
• Transplanted
    acting drugs. They are also critically preload

•   Rejection and infection are the leading causes of
    mortality before 1 year, allograft CAD beyond 1

•   Ask about exercise tolerance

•   Be really clean! They are immunosuppressed.

•   You can use the anesthetic technique that suits the
    patient and the surgery as long as you know what
    you are doing!

•   A Practical Approach to Cardiac Anesthesia, Fourth Edition, 2008. Hensley
    FA, Martin DE, Gravlee GP.
    Chapter 14: Anesthetic Management of Cardiac Transplantation: 439 – 463.
    Thomas Z, Rother AL, Collard CD.

•   A.Curr Opin Anaesthesiol. 2009 Feb; 22(1):109-13. Review. Anaesthesia for
    noncardiac surgery in the heart transplant recipient. Blasco LM,
    Parameshwar J, Vuylsteke

•   Ann Card Anaesth. 2009 Jan-Jun; 12(1):71-8. Adult cardiac transplantation:
    a review of perioperative management
    Part-I. Ramakrishna H, Jaroszewski DE, Arabia FA.

•   http://en.wikipedia.org/wiki/File:Christiaan_Barnard.jpg

•   http://med.stanford.edu/featured_topics/obituary/shumway/

•   N Engl J Med. 2006 Jul 20; 355 (3): 231-5. Taking heart--cardiac
    transplantation past, present, and future. Hunt SA.

•   Canadian Organ Replacement Register (CORR): Treatment of End-Stage
    Organ Failure in Canada 1999 to 2008; 2010 Annual CORR Report

•   http://www.lhsc.on.ca/About_Us/MOTP/Statistics/index.htm

•   BC Medical Journal, May 2010; Vol. 52, No. 4, page(s) 197-202.
    Cardiac transplantation in British Columbia. Stadnick E, Ignaszewski A.

•   Ann Thorac Surg 1998; 65: 857-858.The Society of Thoracic Surgeons: How
    to Do It, Endomyocardial Biopsy in the Heterotopic Heart Transplant Patient.
    Arzouman DA, Arabia FA, Sethi GK, Copeland JG.

•   www.uwoanesthesia.ca/documents/HeartTransplant.ppt
    Anesthesia for Heart Transplant Presentation, Smitherman A.

•   Induction and Maintainence of immunosuppressive therapy in cardiac
    transplantation. Uptodate.com
    Article by Pham MX, Valantine HA, Hunt SA, Yeon SB, updated Aug 2009.

•   Trillium Gift of Life Network. 2010 April 1. Heart Allocation algorithm.

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