Amanda SmitheramPGY-3 Anesthesia

OutlineAnesthesia for Heart Transplant

History & transplant ratesIndications & ContraindicationsThe Donor HeartPre-operative assessment & considerationsIntraoperative managementPost-operative considerations

Outline IIAnesthesia for the Post-Cardiac Transplant

PatientConsiderations

Rejection The Denervated Heart Cardiac transplant vasculopathy Post-transplant arrythmias Immunosuppressant therapy

History1964 – first heart transplanted into a human

at University of Mississippi1967 – first human to human heart transplant

in South Africa. Patient lived for 18 days.1968 – first Canadian heart transplant in

Montreal1981 – introduction of cyclosporine1981 – first heart transplant in Ontario1983 – first heart-lung transplant in Canada

(UH)

Heart Transplant Rates

Canadian Data from 2003:Heart transplants in 12 hospitals (BC, AB, ON,

PQ, NS)157 transplants in 2003131 on waiting listFrom 1993 to 2003, 375 people died waiting

for transplant

From CIHI: http://secure.cihi.ca/cihiweb/dispPage.jsp?cw_page=home_e

Heart Transplant Rates

In London:

Since 1981, 563 heart transplants performed13 heart transplants in 2007 at UHSeveral recipients have had their hearts for

more than 25 years

From: http://www.lhsc.on.ca/About_Us/MOTP/

Heart Transplant RatesHighest mortality in first six months post-

transplantMortality then 3.4% per year after first six

monthsHalf-life of patient survival

8.9 years 1982 to 199111 years from 2002 to 2005

Improvement in mortality primarily due to:Decreased early mortalityImprovement in immunosuppressive therapy and

treatment of infection

Indications for Transplant

End stage heart failure refractory to medical management

90% due to ideopathic or ischemic dilated cardiomyopathy

Congenital defectsValvular heart diseaseDysfunction of previous transplant

? Becoming more common

Natural History of Heart FailureFailure 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

Indications for Transplant

At the time of transplant, many are NYHA class III or IV

Many have LVEF < 20%Many patients awaiting transplant are on

ionotropic supportPatients may be on mechanical assistance

such as LVAD or IABP

Contraindications to TransplantAbsolute:

Severe elevation in pulmonary vascular resistance (> 6 Woods units)

Psychological factors (drug use)Irreversible renal, hepatic or pulmonary

dysfunctionCo-existing illness with poor prognosisUncontrolled malignancyActive infectious process (Hep B/C)

Contraindications to TransplantRelative:

Age > 55 yearsDiabetes with end-organ damageObesityPrevious malignancyOsteoporosisActive peptic ulcer diseaseAmyloidosis

The Donor HeartDonation usually occurs after brain death

Rare instance of DCDExtensive work-up of potential donorsIdeally:

Young, no CAD, HTN, malignancy, systemic illness

Exclude unstable hemodynamics, ventricular arrythmias, cardiac arrest, sepsis, hypoxemia

Far more patients awaiting transplant than available donors…

The Donor HeartCriteria for donation under continuous reviewCases of “marginal donors”Exceptions made to donor criteria in attempt to

increase number of available heartsMay 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

Pre-operative AssessmentEmergency surgery – time is limited, short noticeHistory & Physical:

Focused on CVS, respiratory system, airwayEtiology of cardiac disease and current statusEvidence of secondary organ involvementSymptoms and functional statusPrevious cardiac surgeryMedical therapy – likely on maximal CHF therapy,

any recent medication adjustmentsMechanical therapy – may have IABP, LVAD,

pacemakers, ICDWhen last ate

Pre-operative AssessmentInvestigations

Extensive work-up by transplant teamBlood work: CBC, lytes, kidney & liver function,

coagulation, group and crossmatchViral screening (Hep, HIV, CMV, EBV)ECG, CXR, PFTEchocardiogram: LV/RV function, pulmonary

hypertension, dilatation, hypertrophySurgical Considerations

Previous sternotomyAnticipated difficult technique?

IntraoperativeTiming of induction is crucial as soon as

donor heart arrives (communication with transplant team)

Minimize pre-operative sedationTime to cardiectomy influenced by previous

sternotomy or ventricular assist devicesMinimizing ischemic time of donor heart

Ideally less than 4 hours

Induction of AnesthesiaMinimize pre-operative sedationPatient in OR and induction begun on arrival

of donor heart to ORSurgical team, CPB & perfusionist readyMonitors:

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

Induction of AnesthesiaTypical cardiac induction:

High doses of opioidsMinimize cardiac depressants (propofol,

vapors)Maintain preoperative ionotropes/assist

devicesRSI:

High doses of opioids (fentanyl 10 mcg/kg)Etomidate 0.3 mg/kgSuccinylcholine 1.5 mg/kg

Maintenance of AnesthesiaGoal is to balance myocardial oxygen supply and demandFailing heart very sensitive to changes in preload and

afterloadMaintain intravascular volume, anticipate volume shifts &

bleedingMaintain contractility and systemic vascular resistanceFilling pressures may not reflect volumes, TEE useful

Balance of opioids, benzos and muscle relaxantsLow volume of inhalational agentsAvoid nitrous oxide

Air emboli Increased pulmonary vascular resistance

Withdrawal of PA catheter into SVC prior to excision

Surgical TechniqueOrthotopic transplant

Patient’s native heart removedBiatrial, bicaval techniques

Heterotopic transplantUncommonPatient’s native heart remains in addition to

donor heartDone in cases of severe pulmonary

hypertensionNative heart maintains right circulationDonor heart functions as LVAD

From: NEJM (2007) 356:e6

From: NEJM (2007) 356:e6

Surgical TechniqueCPB and cooling; heart emptied and aorta clampedExcision 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 anastamosedEngraftment of aorta first allowing reperfusion of

coronariesEngraftment of pulmonary artery

Weaning from CPBEvacuation of air from heartIV corticosteroids prior to reperfusionUsual considerations:

Bleeding, valves, air, aorta, rate, rhythm, ischemia, myocardial function

Temp, Hgb, lytes, ventilation, oxygenationPlus:

Denervated heartDysrhythmiasRight heart failure

The Denervated HeartElectrical activity cannot cross suture line

Recipient atrial activity present but not conductedDonor atrium denervated but source of electrophysiologic

responseLoss of SNS, PNS innervation to donor heart

Vagal stimulation has no effect on sinus and AV nodesNo reflex tachycardia in response to hypovolemia,

hypotensionECG has 2 P wavesIndirect sympathomimetic agents have no effect

Anticholinergics, anticholinesterases, pancuronium, ephedrine

Direct acting sympathomimetics work isoproterenol, NE, epi, phenylephrine, dopamine

CPB separationMay develop bradyarrythmias

Require direct acting sympathomimetics, pacingMost grafts recover normal ventricular function

Dysfunction secondary to ischemiaConcern with early recognition of right ventricular

failureRV failure

PVR > 4 Woods units with little or no reversibility preop

Low CO with elevated CVP (> 15) and elevated PAP (> 40). PCWP may be low.

Management of Right Heart FailureOptimize preload – avoid overdistension and

underfillingIonotropic & Chronotropic support -

milrinone, dobutamineMaintain coronary perfusion – vasopressorsLower PVR – nitrates, prostaglandins, NOMechanical support – IABP, RV assist device

Other Post-transplant ProblemsLeft ventricular failureBleeding- higher incidence if anticoagulated

preoperatively for assist devicesDysrhythmias (bradycardia, AV node dysfunction)

Pacing and chronotropes for several weeks4-7% require permanent pacemaker

HypovolemiaAnastamotic obstructionHyperacute rejection

occurs after reperfusion, results from preformed antibodies to donor antigen

Post-transplant Arrythmias

More common in early post-op periodAcute:

Surgical trauma, ischemia, suture linesChronic:

Rejection (involvement of conduction system), cardiac transplant vasculopathy

Post-Transplant ArrythmiasBradyarrythmias/Conduction Abnormalities

Sinus node dysfunctionMay require pacemakerUp to 50% of patients in first several weeksLess frequent with bicaval anastamosis, higher

incidence with prolonged ischemic timeNew right bundle in up to 70%

SVTControl of ventricular rate, overdrive pacing,

ablation Ventricular arrythmias

PVCs common post-op; sustained VT/VF uncommon

Post-transplant PatientsDue 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

Post-Transplant Considerations

Hemodynamic function of denervated heartCardiac transplant vasculopathyAllograft rejectionImmunosuppressive drugs and side effects

Interaction of immunosuppressive drugs and anesthetic agents

Risk of infection

Hemodynamic functionAssess clinically with regard to functional status and

review ECGs, EchoHas the patient required implantation of a

pacemaker for persistent bradyarrythmias?Transplanted, denervated heart is preload dependant

and cannot compensate acutely for hypotensionAdequate pre-operative hydration

Sympathetic and parasympathetic re-innervation?Improved exercise tolerance, LV re-inervation (Bengel,

2002)Vagal re-innervation ~ 4 years post (Uberfuhr, 2000)

Hemodynamic function

No hemodynamic response to direct laryngoscopy

No hemodynamic response to light anesthesia and painRequires careful titration and monitoring of

anestheticIntraoperative hypotension will require

assessment of volume status, adequate preload and direct acting sympathomimetic agents

Cardiac Transplant VasculopathyDiffuse, concentric intimal hyperplasia of

coronary arteriesPatients followed b/w 1994 & 2006:

7% at 1 year, 32% at 5 years, 53% at 10 yearRisk only slightly greater in patients with IHD as

cause of original heart diseaseRisk 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

Cardiac Transplant VasculopathyMay be asymptomaticSilent MI, sudden death, progressive heart

failureHigh mortality

> 40% stenosis – survival 17% at 5 yearsDiagnosis:

Baseline angiography then yearly (1st 5 years)Intravascular ultrasoundTIMI frame countDopplerDobutamine stress test, CT angiography

Cardiac Transplant Vasculopathy Prevention:

Statins, sirolimus, diltiazemTreatment:

Immunosuppressive therapy - ? Regression but increased risk of infection

PCI – efficacy unprovenCABG – difficult due to diffuse nature of

diseaseRetransplantation

Organ RejectionCellular (lymphocyte infiltration) or humoral

(antibody mediated)May be asymptomaticCan be manifest as:

Myocardial dysfunctionDysrhythmiasCoronary atherosclerosis

Time course:Hyperacute – first 24 hr post transplantAcute – occuring within first 6 to 8 weeks Chronic – months to years after transplant

Organ Rejection

Higher risk of rejection:Female donorFemale recipientHigh number of HLA mismatchesYounger recipient

Organ RejectionIdentification usually via biopsySurveillance:

Endomyocardial biopsiesWeekly for first 4 weeksEvery other week for next 6 weeksMonthly for next 3-4 monthsStretched 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

Acute Allograft Rejection6% of deaths in first month, 10% in first to third

yearsDue to surveillance, most diagnosed by

endomyocardial biopsy when patient asymptomatic

Biopsy scheduleWeekly for first 4 weeksEvery other week for next 6 weeksMonthly for next 3-4 months

Symptoms due to LV dysfunction (dyspnea, PND, orthopnea, syncope)

Arrythmias may be common

Immunosuppressive AgentsPost-transplant patient is on life-long

treatmentList of pre-operative medications:

Specific medicationsRecent changes in dose/medicationSide effects from immunosupression

Toxic effects of drugs Infection

Immunosuppressive AgentsInhibition of T cells

Prednisolone, orthoclone (OKT3), 15-Deoxyspergualin

Osteoporosis, DM, glaucoma, bone marrow supression, lymphoproliferative disease, pulmonary edema, neuropathies

Inhibition of Adhesion moleculesAntithymocyte globulins, OKT4AFever, nausea, CMV infection

Immunosuppressive AgentsInhibitions of Cytokine synthesis

Cyclosporin, tacrolimusNephrotoxicity, hepatotoxicity

Inhibition of DNA synthesisAzathioprine, mycophenolate mofetilMyelosupression, malignancy

(lymphoproliferative, cutaneous)

Immunosuppressive AgentsInteraction with anesthetic agents

Several modulate P450 enzymesBarbituates, fentanyl, isofluraneAnimal studies, uncertain clinical significanceNo evidence for alteration of anesthetic practice

Increased risk of infectionsAssess for infection pre-operativelyStrict aseptic techniqueHigher morbidity and mortality if acquires

infection