anesthesia for heart transplant
TRANSCRIPT
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