Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download The heart transplant patient
Document related concepts
Management of acute coronary syndrome wikipedia , lookup
Baker Heart and Diabetes Institute wikipedia , lookup
Coronary artery disease wikipedia , lookup
Cardiac contractility modulation wikipedia , lookup
Heart failure wikipedia , lookup
Arrhythmogenic right ventricular dysplasia wikipedia , lookup
Myocardial infarction wikipedia , lookup
Electrocardiography wikipedia , lookup
Antihypertensive drug wikipedia , lookup
Cardiac surgery wikipedia , lookup
Transcript
The heart transplant patient Dr Christopher Walker Chair, Anaesthesia & Critical Care Harefield Hospital Royal Brompton & Harefield Hospitals, London REGISTRY DATABASE: Number of Transplants Reported ORGAN Heart Heart-Lung Lung Transplants Reported Total Transplants from July 1, 2012, through Reported through June June 30, 2013 30, 2013 Adult Pediatric Adult Pediatric 3,300 508 104,027 11,694 56 10 3,772 694 3,453 97 47,647 1,985 JHLT. 2014 Oct; 33(10): 975-984 REGISTRY DATABASE: Number of Centers Reporting Heart Transplants JHLT. 2014 Oct; 33(10): 975-984 REGISTRY DATABASE: Number of Centers Reporting Heart-Lung Transplants JHLT. 2014 Oct; 33(10): 975-984 Adult Heart Transplants Diagnosis by Age Group (Transplants: January 2006 – June 2013) JHLT. 2014 Oct; 33(10): 996-1008 Consider: • • • • Unique physiological differences Pathologies associated with transplantation Consequences of immunosuppression Anaesthetic challenges Consider: • Unique physiological differences • Pathologies associated with transplantation • Consequences of immunosuppression • Anaesthetic challenges Pathophysiology • Anatomy/Conduction/Denervaton • Vasculopathy • Arryhthmias Anatomical/Physiological Differences • Cuff of native right atrium and donor atrium – Native sinus signal not conducted to donor atria • Bicaval anastamoses commonplace now • Atrial contraction asynchronous – Reduced contribution to ventricular filling (esp. LV) • A-V valves regurgitant – Distorted atria may render mitral and tricuspid incompetent Denervation • Efferent and afferent nerve fibres transected • Vagal tone (dominant inhibition) lost • Resting HR 90-110bpm – Donor SA node sets HR • No reflex autonomic responses – Valsava/carotid sinus massage/Trendelenburg • Hypovolaemia/Haemorrhage – Unable to mount reflex tachycardia to increase CO – No neuro-hormonal drive • Can only increase CO by increasing preload – i.e. dependent on venous return • Systemic catecholamine rise will increase CO – Some delay • => CO is Pre-load dependent • Reinnervation can occur – unpredictable • Sympathetic – After 1 year, commoner when few rejection episodes – Exercise tolerance improves • Parasympathetic – Less predictable – Acetylcholine esterase inhibitors Streichert LC, Sargent PB. J Physiol. 1992 445:249-60 Pharmacological consequences • No autoimmune input to heart – Drugs dependent on autonomic reflexes do not alter heart rate – e.g. atropine, digoxin, pancuronium • No change in heart rate with afterload changes – e.g. nitroprusside, nicardipine, phenylephrine • Opioid induced bradycardia absent • Anticholinesterase inhibitors – no bradycardia So….. • Direct agonists required to increase heart rate – e.g. adrenaline, isoprenaline, dobutamine • Response may be altered due to β-adreno-ceptor supersensitivity • Drugs inducing catecholamine release from adrenergic nerves less effective – e.g. ephedrine Cardiac dysrhythmias • Cardiac dysrhythmias are common – Also used as a predictor of rejection. • Likely due to no vagal tone, rejection episodes, and raised endogenous catecholamines. • New arrhythmias – must consider coronary vasculopathy or rejection. • 1° AV block is common – SA node increased refractory period, atrial conduction prolonged • 5-10% incidence of incomplete/complete right bundle branch block • 20% of heart transplanted patients requires a pacemaker for bradyarrhythmias. Antiarrhythmics • Atropine has no effect in the denervated heart • Class IA antiarrhythmics e.g. procainamide – Effective in treatment of SVT or atrial flutter. – But no tachycardia is mounted -reveals their potent negative inotropy after heart transplantation. • Class IB drugs e.g. lidocaine suppress ventricular automaticity – have no autonomic dependency – Effective in the denervated heart. • Class II - b blocking drugs –normal activity • Class III – e.g. amiodarone – normal activity • Class IV – Ca2+ channel blockers- suppress the sinus and AV-nodes – normal activity – NB significant negative inotropy - Avoid • Digoxin – Vagally mediated AV conduction so less effective • Adenosine – Terminates SVTs – Direct SA node suppression and delaying of His conduction Consider: • Unique physiological differences • Pathologies associated with transplantation • Consequences of immunosuppression • Anaesthetic challenges Cardiac allograft vasculopathy (CAV) -Diffuse, non-focal -Distal & proximal -Concentric thickening -Intimal hyperplasia -Less distinct lipid core -No chest pain!! • Donor Factors Age (>50y), Sex (M) History of hypertension, diabetes, smoking ? Donor Transmitted Atherosclerosis Hepatitis B & C infection • Recipient Factors Age (>40y), Sex (M) Hypertension, dyslipidemia, obesity, smoking, diabetes Hepatitis B • Donor – Recipient Interaction Rejection (cellular and antibody mediated) CMV disease Schematic representation of a model for the pathogenesis of cardiac allograft vasculopathy (CAV) shows central role of immune activation. Mitsuaki Isobe et al. Arterioscler Thromb Vasc Biol. 2006;26:1 1456 Adult Heart Transplants Freedom from Cardiac Allograft Vasculopathy by Transplant Type and Gender (Transplants: April 1994 – June 2012) All pair-wise comparisons with Primary/Female were significant at p < 0.05. No other pair-wise comparisons were significant at p < 0.05. JHLT. 2014 Oct; 33(10): 996-1008 Cardiac allograft vasculopathy • Heart Lung Tx protected from CAV – CAV-free survival rate at 4y & 10y – HLTx 95% & 69%, HTx 77% & 39% • After 5y post transplant: – HTx: malignancy most likely cause of death – HLTx: more likely to die bronchiolitis obliterans J Heart Lung Trans 2014; 33(6):636-43 Other co-morbidities • • • • • • • Diabetes Renal Impairment Hypertension Epilepsy Infection (immuno-compromised) Hyperlipidaemia Gout Consider: • Unique physiological differences • Pathologies associated with transplantation • Consequences of immunosuppression • Anaesthetic challenges Immunosuppression Triple therapy - Post-transplant Ciclosporin/Tacrolimus (calcineurin inhibitors) + Mycophenylate/Azathioprine/Sirolomus (antiproliferative agents) + Prednisolone Long term doses are reduced and sometime prednisolone discontinued Immunosuppression Immunosuppression • 30% renal dysfunction in first year (ciclosporin) – 5% renal replacement Rx Hypertension 70% Diabetes Malignancy Bone marrow depression (thrombocytopaenia, leucopenia) • Seizure threshold reduced (ciclosporin/tacrolimus) • • • • Immunosuppression considerations • Renal impairment & drug clearance • Steroid side effects – Hypertension, hypercholesterolaemia, diabetes • • • • Liver function & cytochrome p450 handled drugs Delayed wound healing Increased risk of infection Specific drug interactions – e.g. ciclosporin prolongs vecuronium action Summar y Steroids Mycophenolate mofetil Antithymocyte globulin OKT3 + - + - - - + - + + + - - + - + - - HTN ++ + - + - - - DM + ++ - ++ - - - Neurotoxicity + + - + - - - Renal Insufficiency + ++ - - - - - Anaphylaxis - - - - - + + Fever - - - - - + + Cyclosporin Tacrolimu s Azathioprine Anaemia - - Leucopenia - Thrombocytopenia Consider: • Unique physiological differences • Consequences of immunosuppression • Pathologies associated with transplantation • Anaesthetic challenges Anaesthesia considerations • >110 000 HTx since 1982 • Survival: 85% at 1y, 75% at 5y, 55% at 10y • <30% return to work • Present for diseases both related and unrelated to transplant Adult and Pediatric Heart Transplants Kaplan-Meier Survival by Age Group (Transplants: January 1982 – June 2013) p < 0.0001 JHLT. 2014 Oct; 33(10): 1009-1024 JHLT. 2015 Oct; 34(10): 1244-1254 Adult and Pediatric Heart Transplants Recipient Age Distribution by Location (Transplants: January 2009 – June 2014) Recipient age (years): mean/median Europe = 47/52 JHLT. 2015 Oct; 34(10): 1244-1254 North America = 45/53 JHLT. 2014 Oct; 33(10): 996-1008 Other = 44/48 Anaesthesia considerations: Preoperative • • • • • Evaluate current cardiac function History Exercise tolerance Episodes of rejection Immunosuppression schedule Preoperative: cardiology • Echocardiography – Assess ventricular and valvular function TV/MV • ECG/Electrophysiology – 1o Block, RBBB? – Pacemaker/ICD check? • Recent cardiac catheter +/- biopsy? • Brain natriuretic peptide? – Often elevated HTx, more so in rejection/CAV? Anaesthesia considerations: Preoperative: cardiology Heterotopic heart transplant Preoperative: Other • • • • Kidney Liver Bone marrow Hyperkalaemia/hypomagnesaemia • All assessed with laboratory testing – BUN/Creat/Electr/AST/ALT/PT/INR/Blood count Preoperative: Other • Immunosuppression – continue – Transplant advice if ciclosporin iv rather than oral • Corticosteroid supplementation – Additional prednisolone – hydrocortisone per-operatively • Antibiotic prophylaxis advice • Premedication if indicated Anaesthesia • General/Regional/Sedation – Avoid acute vasodilatation, hypotension, hypovol. • Monitoring – Invasive if indicated or poor cardiac function • Slow, titrated induction • Preload-dependent – maintain • Supraglottic airway/LMA not contraindicated Anaesthesia • CVS support drugs must have direct action – Isoprenaline, metaraminol, phenylephrine, dobutamine, adrenaline, dopamine, noradrenaline • Antiarrhythmics available e.g. amiodarone • Renally excreted drugs caution – Muscle relaxants, opioids • NSAIDs contraindicated Anaesthesia • Pre-load dependent – High filling pressures, low-normal LVEF, restrictive physiology with increase end diastolic/systolic volumes • Sensitive to reduced HR &/or afterload –will reduce cardiac output – CO dependent on HR as stroke volume relatively fixed • No sympathetic opposition – drop in CO will lead to further reduction in CO and HR Anaesthesia Neuromuscular blocking drugs Cis-atracurium? – no renal excretion Anticholinesterase inhibitors – no bradycardia BUT reports of cardiac arrest following neostgimine to reverse NDNMBs • Sugammadex has been used in a HTx patient • • • • J Cardiothor Vasc Anesth (2013) 27 (6) 1374-8 J Cardiothor Vasc Anesth (2015) In press Summary • Unique physiology of transplanted heart • Denervation and consequent pharmacological differences • Immunosuppression & its consequences – Must continue • Appropriate investigations – Minimum - echocardiogram • Preload & direct vasoactive drugs Further reading Current Opinion in Anaesthesiology Vol 22(1), February 2009, p 109–113 Anaesthesia for noncardiac surgery in the heart transplant recipient Blasco, Lucrecia María; Parameshwar, Jayan; Vuylsteke, Alain Thank you Acknowledgement
