Anesthesia for Heart Transplant

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Anesthesia for Heart Transplant

• Amanda Smitheram
• PGY-3 Anesthesia

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Outline

• Anesthesia for Heart Transplant
• History transplant rates
• Indications Contraindications
• The Donor Heart
• Pre-operative assessment considerations
• Intraoperative management
• Post-operative considerations

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Outline II

• Anesthesia for the Post-Cardiac Transplant
  Patient
• Considerations
• Rejection
• The Denervated Heart
• Cardiac transplant vasculopathy
• Post-transplant arrythmias
• Immunosuppressant therapy

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History

• 1964 first heart transplanted into a human at
  University of Mississippi
• 1967 first human to human heart transplant in
  South Africa. Patient lived for 18 days.
• 1968 first Canadian heart transplant in
  Montreal
• 1981 introduction of cyclosporine
• 1981 first heart transplant in Ontario
• 1983 first heart-lung transplant in Canada (UH)

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Heart Transplant Rates

• Canadian Data from 2003
• Heart transplants in 12 hospitals (BC, AB, ON,
  PQ, NS)
• 157 transplants in 2003
• 131 on waiting list
• From 1993 to 2003, 375 people died waiting for
  transplant

From CIHI http//secure.cihi.ca/cihiweb/dispPage.
jsp?cw_pagehome_e
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Heart Transplant Rates

• In London
• Since 1981, 563 heart transplants performed
• 13 heart transplants in 2007 at UH
• Several recipients have had their hearts for more
  than 25 years

From http//www.lhsc.on.ca/About_Us/MOTP/
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Heart Transplant Rates

• Highest mortality in first six months
  post-transplant
• Mortality then 3.4 per year after first six
  months
• Half-life of patient survival
• 8.9 years 1982 to 1991
• 11 years from 2002 to 2005
• Improvement in mortality primarily due to
• Decreased early mortality
• Improvement in immunosuppressive therapy and
  treatment of infection

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Indications for Transplant

• End stage heart failure refractory to medical
  management
• 90 due to ideopathic or ischemic dilated
  cardiomyopathy
• Congenital defects
• Valvular heart disease
• Dysfunction of previous transplant
• ? Becoming more common

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Natural History of Heart Failure

• Failure of left ventricle leads to an increase in
  left ventricular end-diastolic volume (LVEDP)
  LV hypertrophy
• Enhancement of resting myocardial fibre length
  and more effective contraction
• Stroke volume maintained at expense of increasing
  left atrial pressure, increased diastolic
  pressures and increased pulmonary venous
  congestion
• CO maintained by elevations in catecholamines and
  renin production

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Indications for Transplant

• At the time of transplant, many are NYHA class
  III or IV
• Many have LVEF lt 20
• Many patients awaiting transplant are on
  ionotropic support
• Patients may be on mechanical assistance such as
  LVAD or IABP

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Contraindications to Transplant

• Absolute
• Severe elevation in pulmonary vascular resistance
  (gt 6 Woods units)
• Psychological factors (drug use)
• Irreversible renal, hepatic or pulmonary
  dysfunction
• Co-existing illness with poor prognosis
• Uncontrolled malignancy
• Active infectious process (Hep B/C)

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Contraindications to Transplant

• Relative
• Age gt 55 years
• Diabetes with end-organ damage
• Obesity
• Previous malignancy
• Osteoporosis
• Active peptic ulcer disease
• Amyloidosis

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The Donor Heart

• Donation usually occurs after brain death
• Rare instance of DCD
• Extensive work-up of potential donors
• Ideally
• Young, no CAD, HTN, malignancy, systemic illness
• Exclude unstable hemodynamics, ventricular
  arrythmias, cardiac arrest, sepsis, hypoxemia
• Far more patients awaiting transplant than
  available donors

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The Donor Heart

• Criteria for donation under continuous review
• Cases of marginal donors
• Exceptions made to donor criteria in attempt to
  increase number of available hearts
• May make exceptions for
• Older donors, decreased ejection fraction, left
  ventricular hypertrophy
• Decisions made on individual basis by transplant
  team
• Based on donor characteristics and recipient
  characteristics
• Should be aware of status of donor heart as may
  impact anesthetic management

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Pre-operative Assessment

• Emergency surgery time is limited, short notice
• History Physical
• Focused on CVS, respiratory system, airway
• Etiology of cardiac disease and current status
• Evidence of secondary organ involvement
• Symptoms and functional status
• Previous cardiac surgery
• Medical therapy likely on maximal CHF therapy,
  any recent medication adjustments
• Mechanical therapy may have IABP, LVAD,
  pacemakers, ICD
• When last ate

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Pre-operative Assessment

• Investigations
• Extensive work-up by transplant team
• Blood work CBC, lytes, kidney liver function,
  coagulation, group and crossmatch
• Viral screening (Hep, HIV, CMV, EBV)
• ECG, CXR, PFT
• Echocardiogram LV/RV function, pulmonary
  hypertension, dilatation, hypertrophy
• Surgical Considerations
• Previous sternotomy
• Anticipated difficult technique?

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Intraoperative

• Timing of induction is crucial as soon as donor
  heart arrives (communication with transplant
  team)
• Minimize pre-operative sedation
• Time to cardiectomy influenced by previous
  sternotomy or ventricular assist devices
• Minimizing ischemic time of donor heart
• Ideally less than 4 hours

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Induction of Anesthesia

• Minimize pre-operative sedation
• Patient in OR and induction begun on arrival of
  donor heart to OR
• Surgical team, CPB perfusionist ready
• Monitors
• Standard CAS monitors 5 lead ECG, NIBP, pulse
  oximeter, awake arterial line, lg. bore IVs
• CV access (left IJ), /- PA catheter, nasal temp
  probe
• Continue existing ionotropes, pressors, and
  assist devices

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Induction of Anesthesia

• Typical cardiac induction
• High doses of opioids
• Minimize cardiac depressants (propofol, vapors)
• Maintain preoperative ionotropes/assist devices
• RSI
• High doses of opioids (fentanyl 10 mcg/kg)
• Etomidate 0.3 mg/kg
• Succinylcholine 1.5 mg/kg

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Maintenance of Anesthesia

• Goal is to balance myocardial oxygen supply and
  demand
• Failing heart very sensitive to changes in
  preload and afterload
• Maintain intravascular volume, anticipate volume
  shifts bleeding
• Maintain contractility and systemic vascular
  resistance
• Filling pressures may not reflect volumes, TEE
  useful
• Balance of opioids, benzos and muscle relaxants
• Low volume of inhalational agents
• Avoid nitrous oxide
• Air emboli
• Increased pulmonary vascular resistance
• Withdrawal of PA catheter into SVC prior to
  excision

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Surgical Technique

• Orthotopic transplant
• Patients native heart removed
• Biatrial, bicaval techniques
• Heterotopic transplant
• Uncommon
• Patients native heart remains in addition to
  donor heart
• Done in cases of severe pulmonary hypertension
• Native heart maintains right circulation
• Donor heart functions as LVAD

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From NEJM (2007) 356e6
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From NEJM (2007) 356e6
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Surgical Technique

• CPB and cooling heart emptied and aorta clamped
• Excision of native heart aorta, pulmonary
  artery, left and right atria (at AV groove),
  ventricles resected
• Biatrial biatrial cuff remains with venal caval
  and pulmonary venous connections
• Bicaval donor right atrium removed intact with
  venae cavae intact for anastamosis
• Great arteries anastamosed
• Engraftment of aorta first allowing reperfusion
  of coronaries
• Engraftment of pulmonary artery

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Weaning from CPB

• Evacuation of air from heart
• IV corticosteroids prior to reperfusion
• Usual considerations
• Bleeding, valves, air, aorta, rate, rhythm,
  ischemia, myocardial function
• Temp, Hgb, lytes, ventilation, oxygenation
• Plus
• Denervated heart
• Dysrhythmias
• Right heart failure

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The Denervated Heart

• Electrical activity cannot cross suture line
• Recipient atrial activity present but not
  conducted
• Donor atrium denervated but source of
  electrophysiologic response
• Loss of SNS, PNS innervation to donor heart
• Vagal stimulation has no effect on sinus and AV
  nodes
• No reflex tachycardia in response to hypovolemia,
  hypotension
• ECG has 2 P waves
• Indirect sympathomimetic agents have no effect
• Anticholinergics, anticholinesterases,
  pancuronium, ephedrine
• Direct acting sympathomimetics work
• isoproterenol, NE, epi, phenylephrine, dopamine

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CPB separation

• May develop bradyarrythmias
• Require direct acting sympathomimetics, pacing
• Most grafts recover normal ventricular function
• Dysfunction secondary to ischemia
• Concern with early recognition of right
  ventricular failure
• RV failure
• PVR gt 4 Woods units with little or no
  reversibility preop
• Low CO with elevated CVP (gt 15) and elevated PAP
  (gt 40). PCWP may be low.

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Management of Right Heart Failure

• Optimize preload avoid overdistension and
  underfilling
• Ionotropic Chronotropic support - milrinone,
  dobutamine
• Maintain coronary perfusion vasopressors
• Lower PVR nitrates, prostaglandins, NO
• Mechanical support IABP, RV assist device

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Other Post-transplant Problems

• Left ventricular failure
• Bleeding- higher incidence if anticoagulated
  preoperatively for assist devices
• Dysrhythmias (bradycardia, AV node dysfunction)
• Pacing and chronotropes for several weeks
• 4-7 require permanent pacemaker
• Hypovolemia
• Anastamotic obstruction
• Hyperacute rejection
• occurs after reperfusion, results from preformed
  antibodies to donor antigen

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Post-transplant Arrythmias

• More common in early post-op period
• Acute
• Surgical trauma, ischemia, suture lines
• Chronic
• Rejection (involvement of conduction system),
  cardiac transplant vasculopathy

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Post-Transplant Arrythmias

• Bradyarrythmias/Conduction Abnormalities
• Sinus node dysfunction
• May require pacemaker
• Up to 50 of patients in first several weeks
• Less frequent with bicaval anastamosis, higher
  incidence with prolonged ischemic time
• New right bundle in up to 70
• SVT
• Control of ventricular rate, overdrive pacing,
  ablation
• Ventricular arrythmias
• PVCs common post-op sustained VT/VF uncommon

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Anesthetic Considerations for the Post-heart
Transplant Patient
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Post-transplant Patients

• Due to improvements in immunosuppressive
  therapies and treatment of infection, more
  patients are surviving longer after heart
  transplant
• May be caring for increasing numbers of
  transplant patients who present for other
  surgeries
• In addition to the usual anesthetic
  considerations, there are particular
  considerations for the heart transplant patient

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Post-Transplant Considerations

• Hemodynamic function of denervated heart
• Cardiac transplant vasculopathy
• Allograft rejection
• Immunosuppressive drugs and side effects
• Interaction of immunosuppressive drugs and
  anesthetic agents
• Risk of infection

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Hemodynamic function

• Assess clinically with regard to functional
  status and review ECGs, Echo
• Has the patient required implantation of a
  pacemaker for persistent bradyarrythmias?
• Transplanted, denervated heart is preload
  dependant and cannot compensate acutely for
  hypotension
• Adequate pre-operative hydration
• Sympathetic and parasympathetic re-innervation?
• Improved exercise tolerance, LV re-inervation
  (Bengel, 2002)
• Vagal re-innervation 4 years post (Uberfuhr,
  2000)

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Hemodynamic function

• No hemodynamic response to direct laryngoscopy
• No hemodynamic response to light anesthesia and
  pain
• Requires careful titration and monitoring of
  anesthetic
• Intraoperative hypotension will require
  assessment of volume status, adequate preload and
  direct acting sympathomimetic agents

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Cardiac Transplant Vasculopathy

• Diffuse, concentric intimal hyperplasia of
  coronary arteries
• Patients followed b/w 1994 2006
• 7 at 1 year, 32 at 5 years, 53 at 10 year
• Risk only slightly greater in patients with IHD
  as cause of original heart disease
• Risk factors
• Donor age, recipient age, male, donor HTN,
  earlier year of transplant and HLA-DR mismatches
• Associated with acute antibody-mediated rejection
• Can have rapid progression

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Cardiac Transplant Vasculopathy

• May be asymptomatic
• Silent MI, sudden death, progressive heart
  failure
• High mortality
• gt 40 stenosis survival 17 at 5 years
• Diagnosis
• Baseline angiography then yearly (1st 5 years)
• Intravascular ultrasound
• TIMI frame count
• Doppler
• Dobutamine stress test, CT angiography

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Cardiac Transplant Vasculopathy

• Prevention
• Statins, sirolimus, diltiazem
• Treatment
• Immunosuppressive therapy - ? Regression but
  increased risk of infection
• PCI efficacy unproven
• CABG difficult due to diffuse nature of disease
• Retransplantation

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Organ Rejection

• Cellular (lymphocyte infiltration) or humoral
  (antibody mediated)
• May be asymptomatic
• Can be manifest as
• Myocardial dysfunction
• Dysrhythmias
• Coronary atherosclerosis
• Time course
• Hyperacute first 24 hr post transplant
• Acute occuring within first 6 to 8 weeks
• Chronic months to years after transplant

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Organ Rejection

• Higher risk of rejection
• Female donor
• Female recipient
• High number of HLA mismatches
• Younger recipient

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Organ Rejection

• Identification usually via biopsy
• Surveillance
• Endomyocardial biopsies
• Weekly for first 4 weeks
• Every other week for next 6 weeks
• Monthly for next 3-4 months
• Stretched out to yearly or every other year
• New molecular test for screening (not widely
  used)
• Important to note presence and degree of
  rejection prior to surgery
• Treatment of acute rejection may be required
  prior to surgery

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Acute Allograft Rejection

• 6 of deaths in first month, 10 in first to
  third years
• Due to surveillance, most diagnosed by
  endomyocardial biopsy when patient asymptomatic
• Biopsy schedule
• Weekly for first 4 weeks
• Every other week for next 6 weeks
• Monthly for next 3-4 months
• Symptoms due to LV dysfunction (dyspnea, PND,
  orthopnea, syncope)
• Arrythmias may be common

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Immunosuppressive Agents

• Post-transplant patient is on life-long treatment
• List of pre-operative medications
• Specific medications
• Recent changes in dose/medication
• Side effects from immunosupression
• Toxic effects of drugs
• Infection

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Immunosuppressive Agents

• Inhibition of T cells
• Prednisolone, orthoclone (OKT3),
  15-Deoxyspergualin
• Osteoporosis, DM, glaucoma, bone marrow
  supression, lymphoproliferative disease,
  pulmonary edema, neuropathies
• Inhibition of Adhesion molecules
• Antithymocyte globulins, OKT4A
• Fever, nausea, CMV infection

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Immunosuppressive Agents

• Inhibitions of Cytokine synthesis
• Cyclosporin, tacrolimus
• Nephrotoxicity, hepatotoxicity
• Inhibition of DNA synthesis
• Azathioprine, mycophenolate mofetil
• Myelosupression, malignancy (lymphoproliferative,
  cutaneous)

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Immunosuppressive Agents

• Interaction with anesthetic agents
• Several modulate P450 enzymes
• Barbituates, fentanyl, isoflurane
• Animal studies, uncertain clinical significance
• No evidence for alteration of anesthetic practice
• Increased risk of infections
• Assess for infection pre-operatively
• Strict aseptic technique
• Higher morbidity and mortality if acquires
  infection