Anaesthesia for Organ Transplantation

Quick Answer

Organ transplantation presents unique challenges: Kidney transplant (most common, end-stage renal disease) - avoid nephrotoxins, maintain perfusion, manage hyperkalemia, avoid hypotension post-anastomosis. Liver transplant (fulminant hepatic failure, cirrhosis) - high-risk (complex, massive bleeding), portal hypertension (collaterals, coagulopathy), reperfusion syndrome (post-IVC/portal reperfusion - bradycardia, hypotension, hyperkalemia, acidosis), transfusion requirements (often >20 units), thromboelastography (TEG/ROTEM) guided coagulation management, post-reperfusion pulmonary hypertension. Cardiac transplant (dilated cardiomyopathy, ischemic heart disease) - denervated heart (no vagal tone, direct acting drugs only), pulmonary hypertension (risk of right heart failure), inotrope dependence, rejection surveillance. Lung transplant (COPD, CF, IPF) - pulmonary hypertension, one-lung ventilation for implantation, primary graft dysfunction, reperfusion injury. Pancreas (diabetes): Often with kidney (SPK), risk of pancreatitis. [1-10]

Pathophysiology

Kidney Transplantation

Recipient Considerations:

• End-stage renal disease (ESRD): On dialysis or approaching need
• Pathophysiology:
  • Fluid overload, electrolyte abnormalities (hyperkalemia)
  • Hypertension, cardiovascular disease
  • Anaemia (erythropoietin deficiency)
  • Platelet dysfunction (uremia)
  • Gastroparesis (autonomic neuropathy)
• Dialysis timing: Last dialysis ideally 24 hours pre-op (reduces fluid overload, heparin effect cleared)

Donor Kidney:

• Living donor: Better outcomes, elective, shorter cold ischemia time
• Deceased donor: Brain death effects (catecholamine storm → myocardial stunning, DI), longer cold ischemia
• Cold ischemia time: <24 hours optimal (reduced delayed graft function)

Surgical Considerations:

• Location: Extraperitoneal, iliac fossa (right or left)
• Anastomoses: Renal artery to internal/external iliac, renal vein to external iliac, ureter to bladder
• Reperfusion: "Bleeding" into graft (not surgical bleeding), urine output immediate if graft functions

Key Anaesthetic Issues:

1. Hyperkalemia: Risk from stored blood, preserved solution, reperfusion
2. Hypotension post-reperfusion: Reduces graft perfusion
3. Diuresis: Can be massive (urine output 500-1000 mL/hour)
4. Delayed graft function: No immediate urine output
5. Rejection: Risk reduced with immunosuppression

Liver Transplantation

Indications:

• Acute liver failure: Fulminant hepatic failure (paracetamol, viral hepatitis)
• Chronic liver disease: Cirrhosis (alcohol, hepatitis C, NASH, PSC, PBC)
• Malignancy: Hepatocellular carcinoma (within Milan criteria)

Pathophysiology of Liver Disease:

Portal Hypertension:

• Mechanism: Cirrhosis → increased resistance to portal flow
• Consequences:
  • Varices (oesophageal, gastric)
  • Splenomegaly, hypersplenism (thrombocytopenia)
  • Ascites
  • Portosystemic collaterals (surgical bleeding risk)
• Surgical implications: Massive bleeding from dilated vessels, adhesions from previous surgery

Coagulopathy:

• Impaired synthesis: Factors II, VII, IX, X (vitamin K-dependent), V, XI, fibrinogen
• Thrombocytopenia: Hypersplenism, bone marrow suppression, consumption
• Fibrinolysis: Impaired clearance of tPA
• TEG/ROTEM essential: Guide blood product administration

Cardiovascular:

• Hyperdynamic circulation: High CO, low SVR (vasodilation)
• Cardiomyopathy: Cirrhotic cardiomyopathy (diastolic dysfunction, stress intolerance)
• Portopulmonary hypertension: Pulmonary arterial hypertension (contraindication to transplant if severe)
• Hepatopulmonary syndrome: Intrapulmonary shunts → hypoxia

Other Systemic Effects:

• Renal dysfunction: Hepatorenal syndrome (functional, reversible with new liver)
• Encephalopathy: Ammonia, other neurotoxins
• Ascites: Third spacing, respiratory compromise
• Malnutrition: Low albumin, poor wound healing

Phases of Liver Transplant:

Phase 1: Dissection (Pre-Anhepatic):

• Duration: 1-3 hours
• Activities: Mobilization liver, portal dissection, hepatectomy
• Challenges:
  • Massive bleeding (collaterals, adhesions)
  • Coagulopathy (consumption, dilution)
  • Hypotension (venous bleeding, vasodilation)
  • Hypocalcemia (citrate from blood products)

Phase 2: Anhepatic:

• Duration: 30 minutes to 2 hours (shorter with piggyback technique)
• No liver function:
  • No glucose production (hypoglycemia)
  • No lactate clearance (acidosis)
  • No clotting factor production (worsening coagulopathy)
  • No drug metabolism (accumulation)
  • No bile production
• Venous clamping: Portal vein, infrahepatic IVC (or piggyback - partial)
• Veno-venous bypass (if used): Portal vein + femoral vein → axillary vein (decompresses IVC, maintains venous return)

Phase 3: Reperfusion (Neohepatic):

• Critical phase: Unclamping portal vein and IVC
• Reperfusion syndrome:
  • Release of cold, acidotic, hyperkalemic preservation solution into circulation
  • Bradycardia (vagal response)
  • Hypotension (vasodilation, myocardial depression)
  • Arrhythmias (VF, asystole)
  • Pulmonary hypertension (emboli, mediators)
  • Hyperkalemia (cardiac arrest risk)
• Biliary anastomosis: Often after reperfusion

Coagulation Management:

• TEG/ROTEM: Essential (thromboelastography)
  • R-time (clotting time): FFP if prolonged
  • Alpha angle/fibrinogen: Cryoprecipitate if low
  • MA (maximum amplitude): Platelets if low
  • LY30 (lysis): Antifibrinolytics if excessive
• Cell salvage: Essential (autotransfusion)
• Massive transfusion protocol: Often >20 units PRBC

Cardiac Transplantation

Indications:

• Dilated cardiomyopathy: Viral, idiopathic, familial, peripartum
• Ischemic cardiomyopathy: Failed revascularization/reperfusion
• Congenital heart disease: Not amenable to repair
• Valvular disease: Not amenable to surgery

Pathophysiology:

Denervated Heart:

• Surgical transection: Vagal and sympathetic nerves severed during transplant
• Consequences:
  • No vagal tone: Higher resting HR (90-110 bpm)
  • No reflex bradycardia: Response to hypertension (denervated)
  • Direct-acting drugs only: Atropine ineffective (no vagal tone to block), digoxin ineffective (no AV node effect)
  • Denervation supersensitivity: Exaggerated response to catecholamines (upregulated receptors)
  • Exercise limitation: No HR increase anticipation, gradual HR rise (circulating catecholamines)

Pulmonary Hypertension:

• Pre-existing: From left heart failure (reversible with new heart)
• Fixed pulmonary hypertension: Risk of right heart failure with transplantation
  • PAP >60 mmHg or transpulmonary gradient >15 mmHg = high risk
  • May need preoperative management (sildenafil, bosentan)
  • May require RV assist device post-transplant

Surgical Considerations:

• Bicaval vs. biatrial technique: Bicaval preserves atrial function, less arrhythmias
• Cardiopulmonary bypass: Standard
• Cardioplegia: Myocardial protection during implantation
• Reperfusion: Aortic unclamping, defibrillation usually needed

Lung Transplantation

Indications:

• COPD/Emphysema: Most common
• Cystic fibrosis: Younger patients
• Idiopathic pulmonary fibrosis: Rapid progression
• Pulmonary hypertension: Primary or Eisenmenger syndrome

Types:

• Single lung: COPD, IPF (contralateral native lung provides reserve)
• Double lung: CF (bilateral infection), severe pulmonary hypertension
• Heart-lung: Eisenmenger syndrome, severe combined disease

Pathophysiology:

Native Lung Disease:

• COPD: Air trapping, bullae, pulmonary hypertension
• CF: Bronchiectasis, infection (Pseudomonas), hemoptysis
• IPF: Restrictive disease, pulmonary hypertension, hypoxia
• PPH: Right heart failure, low cardiac output

Surgical Considerations:

• One-lung ventilation (OLV): Required for implantation
• Positioning: Lateral decubitus (single), supine (bilateral sequential)
• Pulmonary artery clamping: Test clamp to assess tolerance
• Reperfusion: Release of PA clamp (risk of pulmonary edema, hypotension)

Primary Graft Dysfunction (PGD):

• Definition: Reperfusion injury causing non-cardiogenic pulmonary edema
• Severity: Grade 0-3 based on PaO₂/FiO₂
• Management: Protective ventilation, PEEP, restrictive fluid, ECMO if severe

Pancreas Transplantation

Types:

• Simultaneous pancreas-kidney (SPK): Most common (diabetes with ESRD)
• Pancreas after kidney (PAK): Kidney first, pancreas later
• Pancreas transplant alone (PTA): Diabetes without kidney disease

Surgical Considerations:

• Location: Intraperitoneal (pelvic or mid-abdomen)
• Vascular anastomoses: Arterial (often Y-graft with donor iliac), venous (portal or systemic)
• Exocrine drainage: Bladder (older) or enteric (enteric-anastomosis to bowel)
• Complications: Pancreatitis, thrombosis (graft loss), leak, infection

Clinical Presentation

Preoperative Assessment

General (All Transplants):

• Indication: End-organ failure, suitability
• Comorbidities: Cardiovascular, pulmonary, renal, hepatic
• Previous surgery: Difficult dissection, adhesions
• Blood work: FBC, coagulation, electrolytes, crossmatch
• Infectious screening: Serologies (CMV, EBV, HIV, hepatitis)
• Psychosocial: Compliance with immunosuppression

Specific to Organ:

Kidney:

• Dialysis: Last session, access (fistula, catheter), anticoagulation status
• Volume status: Dry weight, fluid overload?
• Sensitization: Previous transplants, pregnancies, transfusions (high PRA)

Liver:

• MELD/Child-Pugh score: Severity, mortality prediction
• Ascites: Tense? Respiratory compromise?
• Encephalopathy: Grade, ammonia level
• Varices: Bleeding history, banding
• Renal function: Creatinine, hepatorenal syndrome
• Pulmonary: HPS, POPH (contraindications if severe)
• Previous surgery: TIPS, shunts, abdominal surgery (adhesions)

Heart:

• NYHA class: Functional status
• Echocardiography: EF, RV function, valves
• Pulmonary pressures: PAP, PVR (reversibility testing)
• Inotrope dependence: Bridge to transplant
• Mechanical support: IABP, VAD, ECMO
• Arrhythmias: ICD/AICD (deactivate for surgery)

Lung:

• PFTs: Severity, reversibility
• ABG: Baseline hypoxia, CO₂ retention
• Infection: Current antibiotics, colonization
• Pulmonary hypertension: Echo, cath
• Gastroesophageal reflux: Common in CF (aspiration risk)

Management

General Principles

Immunosuppression:

• Induction: Often given in OR or immediately post-op
  • Basiliximab (IL-2 receptor antibody), ATG (anti-thymocyte globulin), alemtuzumab
• Maintenance: Triple therapy (calcineurin inhibitor + antimetabolite + steroid)
  • Tacrolimus or cyclosporine (CNI)
  • Mycophenolate or azathioprine
  • Prednisolone (tapering)
• Drug interactions: Many with anaesthetic agents

Monitoring:

• Standard: ECG, SpO₂, NIBP, EtCO₂, temperature
• Arterial line: Essential for all (beat-to-beat, frequent labs)
• Central line: CVP, PA catheter if indicated
• TEE: Cardiac and liver transplants (assess function, volume, air)
• TEG/ROTEM: Liver transplant (essential)
• Urinary catheter: All cases
• BIS: Optional

Temperature:

• Hypothermia risk: Large exposure, long surgery, cold preservation solution
• Active warming: Forced air, fluid warmers, heated mattress
• Target: Normothermia (36-37°C)

Kidney Transplant Anaesthesia

Induction:

• Propofol or etomidate: Standard
• Fentanyl: Blunt response to stimulation
• Rocuronium: Standard (avoid suxamethonium if hyperkalemic)
• Pre-hydration: 500-1000 mL crystalloid (unless contraindicated)

Maintenance:

• TIVA or balanced: Either acceptable
• Muscle relaxation: Maintain (surgical field)
• Ventilation: Normocapnia (hypercapnia reduces renal blood flow)

Key Management Points:

1. Avoid nephrotoxins:
   • Aminoglycosides (gentamicin)
   • NSAIDs
   • Contrast (if possible)
   • Vancomycin (if used, monitor levels)
2. Maintain perfusion pressure:
   • MAP >70-80 mmHg (post-anastomosis critical)
   • Vasopressors if needed (phenylephrine, noradrenaline)
   • Avoid hypotension (graft perfusion)
3. Hyperkalemia management:
   • Preoperative: Dialysis usually performed
   • Intraoperative: Calcium (stabilize myocardium), insulin/glucose, bicarbonate if needed
   • Post-reperfusion: Monitor closely (preservation solution contains potassium)
4. Fluid management:
   • Pre-reperfusion: Moderate hydration
   • Post-reperfusion: Often massive diuresis (500-1000 mL/hour)
   • Replace urine output mL for mL (0.45% saline + dextrose or balanced crystalloid)
   • Monitor electrolytes (replace K⁺, Mg²⁺)
5. Mannitol: 0.25-0.5 g/kg (osmotic diuretic, free radical scavenger, graft protection)

Postoperative:

• Immunosuppression: Start immediately (tacrolimus, mycophenolate, steroid)
• Diuresis: Continue to manage
• Monitor graft function: Urine output, creatinine
• Delayed graft function: Dialysis may be needed temporarily

Liver Transplant Anaesthesia

Induction:

• Cautious: Hemodynamically unstable common
• Ketamine: Useful if hypotensive (sympathomimetic)
• Etomidate: Hemodynamically neutral
• Propofol: Reduced dose (slow metabolism)
• RSI: Full stomach (ascites, gastroparesis)

Monitoring:

• Arterial line: Radial or femoral (pressure differential if femoral used for bypass)
• Central line: Right IJ (avoid left if possible - collaterals), multiple lumens
• TEE: Essential (volume status, RV function, air detection)
• TEG/ROTEM: Serial testing (q30-60 minutes or as needed)
• Temperature: Core (nasopharyngeal), bladder, skin

Phase-Specific Management:

Phase 1: Dissection:

• Blood loss: Massive (prepare cell salvage, massive transfusion protocol)
• Coagulation: TEG-guided blood products
• Calcium: Monitor ionized Ca²⁺, replace (citrate from blood products binds Ca²⁺)
• Acid-base: Expect metabolic acidosis (lactate from poor clearance)
• Glucose: Monitor (hypoglycemia common, liver not producing glucose)
• Temperature: Actively warm (massive exposure)

Phase 2: Anhepatic:

• No drug metabolism: Accumulation of opioids, benzodiazepines
• Hypoglycemia: Dextrose infusion (10% or 20%)
• Citrate toxicity: Hypocalcemia from massive transfusion (ionized Ca²⁺ <1.0 mmol/L)
• Acidosis: Worsens (lactate accumulation)
• Fibrinolysis: May increase (impaired clearance of tPA)
• Veno-venous bypass (if used):
  • Heparin 3000-5000 units (bypass pump)
  • Flow 2-4 L/min
  • Maintains venous return, decompresses IVC
  • Reduces splanchnic congestion

Phase 3: Reperfusion (Critical):

• Preparation:
  • Calcium ready (ionized Ca²⁺ often low)
  • Bicarbonate (acidosis)
  • Inotropes (adrenaline, noradrenaline)
  • Defibrillator (VF risk)
• Communication: Surgeon announces reperfusion
• Reperfusion syndrome management:
  1. Bradycardia: Atropine 0.5-1 mg, pacing if severe
  2. Hypotension: Vasopressors (phenylephrine, adrenaline), fluids
  3. Hyperkalemia: Calcium (cardiac membrane stabilization), insulin/glucose, bicarbonate
  4. Pulmonary hypertension: Inhaled NO, milrinone, avoid hypoxia/acidosis
  5. Air embolism: TEE monitoring (air in RA/RV common, usually well-tolerated)
• Bile production: Good sign (liver function)

Post-reperfusion:

• Coagulation: Usually improves rapidly (new liver produces factors)
• Hemodynamics: Stabilize, reduce vasopressors as liver clears acid/lactate
• Diuresis: Often starts (if hepatorenal syndrome, may improve with new liver)

Immunosuppression:

• Timing: Usually after graft perfusion
• Agents: Steroids (methylprednisolone 500 mg-1 g), basiliximab, tacrolimus (orally later)

Postoperative:

• ICU: Mandatory
• Complications to monitor:
  • Primary non-function (urgent re-transplant)
  • Hepatic artery thrombosis (Doppler ultrasound)
  • Biliary leak/stricture
  • Acute rejection (biopsy)
  • Infection (immunosuppressed)
  • Renal function (CNI nephrotoxicity)

Cardiac Transplant Anaesthesia

Induction:

• Hemodynamic stability: Critical (patients often decompensated)
• Etomidate or ketamine: Preferred over propofol
• High-dose opioid: Blunt sympathetic response
• Inotropes: Prepared (often needed)

Cardiopulmonary Bypass:

• Standard cannulation: Aorta, right atrium (bicaval if needed)
• Myocardial protection: Cardioplegia
• Duration: Cross-clamp time 2-4 hours typical

Denervated Heart Management:

• Heart rate: Will be 90-110 bpm (no vagal tone)
• Drugs:
  • Direct-acting: Adrenaline, dobutamine, isoprenaline (work directly on receptors)
  • Indirect-acting: Atropine (no effect, no vagal tone to block), digoxin (no AV node effect)
• Sympathomimetics: Exaggerated response (denervation supersensitivity)
• Pacing: Often needed temporarily (junctional rhythm common initially)

Right Ventricular Failure:

• Risk: Pre-existing pulmonary hypertension
• Management:
  • Inhaled nitric oxide (iNO): Selective pulmonary vasodilator
  • Milrinone: Pulmonary vasodilation, inotropy
  • Prostaglandins: Epoprostenol
  • RVAD: If severe (mechanical support)

Weaning from Bypass:

• Inotrope support: Usually required (isoprenaline, adrenaline, milrinone)
• Rate: Maintain 90-100 bpm (pacing or isoprenaline)
• Reperfusion: Aortic unclamping, graft reperfusion

Postoperative:

• ICU: Mechanical ventilation until stable
• Inotropes: Wean as graft function improves
• Denervation: Counsel patient (no chest pain with ischemia, exercise limitations)
• Rejection surveillance: Endomyocardial biopsy, echo

Lung Transplant Anaesthesia

Induction:

• Avoid N₂O: Expands bullae, pneumothorax risk
• Epidural: For postoperative analgesia (placed pre-op)
• Double-lumen tube: For OLV

One-Lung Ventilation:

• Native lung: Ventilated (airway secretions, infection)
• Surgical side: Collapsed for implantation
• Hypoxia: Common (shunt through non-ventilated lung)
• Management: CPAP to surgical lung (if possible), PEEP to native lung, optimize V/Q

Cardiopulmonary Bypass:

• Indications: Severe pulmonary hypertension, hemodynamic instability, OLV not tolerated
• Alternative: ECMO for selective cases

Reperfusion:

• Pulmonary artery unclamping: Gradual (test perfusion)
• Reperfusion pulmonary edema: Risk (PGD)
• Ventilation: Protective strategy (low tidal volume, PEEP, FiO₂ adjusted)

Postoperative:

• Immunosuppression: As protocol
• PGD monitoring: Chest X-ray, ABG, compliance
• Bronchoscopy: Surveillance, clearance
• Physiotherapy: Essential for secretion clearance

Indigenous Health Considerations

Aboriginal and Torres Strait Islander Patients

Higher Disease Burden:

• Diabetes: Higher rates → ESRD, need for kidney/pancreas transplant
• Alcohol-related liver disease: Cirrhosis, need for liver transplant
• Hepatitis B/C: Higher prevalence (liver disease)
• Cardiovascular disease: Cardiomyopathy, ischemic heart disease

Access and Equity:

• Geographic barriers: Transplant centers in major cities (Sydney, Melbourne, Brisbane, Perth)
• Waiting lists: Long waits for kidney (dialysis dependence)
• Retrieval: Organ donation rates lower in some communities
• Family separation: Extended treatment away from country

Cultural Considerations:

• Organ donation: Discuss with family, cultural beliefs
• Compliance: Long-term immunosuppression requires adherence support
• Cultural safety: Aboriginal liaison officers, interpreters

Māori Health Considerations

Health Disparities:

• Higher rates of diabetes and renal disease
• Cardiovascular disease burden
• Access to transplant services

Cultural Considerations:

• Whānau decision-making: Family involvement in transplant decisions
• Organ donation: Cultural perspectives on donation
• Follow-up: Coordination with primary care for immunosuppression
• Tikanga: Respect for cultural practices during illness

ANZCA Final Exam Focus

SAQ Patterns

Common Questions:

• "Describe the anaesthetic management for liver transplantation."
• "What is post-reperfusion syndrome and how do you manage it?"
• "How does the denervated heart respond to drugs differently?"
• "What are the phases of liver transplant and the specific concerns in each?"

Marking Scheme Priorities:

• Liver transplant phases (dissection, anhepatic, reperfusion)
• Reperfusion syndrome (hyperkalemia, bradycardia, hypotension, acidosis)
• Denervated heart physiology (no vagal tone, direct-acting drugs only)
• Coagulation management in liver transplant (TEG/ROTEM)
• Right heart failure in cardiac/lung transplant

Viva Scenarios

Scenario 1: Liver Transplant Reperfusion

• Surgeon announces reperfusion
• HR drops to 40, BP 50/30, K⁺ 6.5 mmol/L
• Management: Calcium, atropine, adrenaline, bicarbonate, inotropes

Scenario 2: Cardiac Transplant

• Patient HR 95 bpm (intrinsic)
• Does not respond to atropine (denervated)
• Direct-acting inotropes needed (adrenaline, isoprenaline)
• Denervation supersensitivity

Scenario 3: Kidney Transplant

• Post-anastomosis, urine output 800 mL in first hour
• Fluid management: Replace mL for mL
• Avoid hypotension (graft perfusion)
• Monitor electrolytes

Key Points for Examination Success

1. Kidney: Avoid nephrotoxins, maintain MAP >70-80 mmHg post-anastomosis, manage hyperkalemia, replace diuresis mL for mL
2. Liver phases: Dissection (bleeding, coagulopathy), anhepatic (no metabolism, hypoglycemia, acidosis), reperfusion (syndrome - bradycardia, hypotension, hyperkalemia)
3. Reperfusion syndrome: Calcium (stabilize heart), atropine (bradycardia), inotropes, bicarbonate (acidosis), prepare for arrest
4. TEG/ROTEM: Essential for liver transplant (R-time = FFP, alpha/fibrinogen = cryoprecipitate, MA = platelets, LY30 = antifibrinolytics)
5. Denervated heart: HR 90-110 intrinsic, no vagal tone (atropine ineffective), direct-acting drugs only, denervation supersensitivity
6. Pulmonary hypertension: Risk of RV failure (inhaled NO, milrinone, prostaglandins)
7. Immunosuppression: Calcineurin inhibitor + antimetabolite + steroid, induction agents often in OR
8. Primary graft dysfunction: Lung reperfusion injury (protective ventilation, restrictive fluids)

References

1. ANZCA. PS54. Statement on Cardiopulmonary Bypass. 2020.
2. Mandell MS et al. Anesthesia for liver transplantation. Anesthesiol Clin. 2017;35(3):491-508.
3. Nakanishi R et al. The current state of the art in liver transplantation. J Clin Med. 2021;10(15):3262.
4. Klinger M et al. The EACTS/ISHLT thoracic transplant guidelines. Eur J Cardiothorac Surg. 2022;61(4):779-826.
5. Augoustides JG et al. Heart transplantation. In: Kaplan's Cardiac Anesthesia. 7th ed. Elsevier; 2017:701-720.
6. Feltracco P et al. Anesthetic considerations for lung transplantation. J Thorac Dis. 2018;10(4):2133-2144.
7. Tavakoli R et al. Kidney transplantation: anaesthetic management. Curr Opin Anaesthesiol. 2021;34(5):621-628.
8. ATSI Health. Chronic kidney disease in Aboriginal and Torres Strait Islander peoples. Australian Institute of Health and Welfare; 2020.