Handbook of Clinical Anesthesia

Chapter 54

Transplant Anesthesia

To optimize organ allocation, the United States is divided into 11 regions for purposes of organ distribution, each with its own regional review board (Ceste M, Glas K: Transplant anesthesia. In Clinical Anesthesia. Edited by Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC. Philadelphia: Lippincott Williams & Wilkins, 2009, pp 1393–1418).

  1. Anesthetic Management of Organ Donors
  2. Brain-Dead Donor.Legal and medical brain death criteria differ from state to state, but all require cessation of both cerebral and brainstem function. Potentially reversible causes of coma or unresponsiveness (hypothermia, hypotension, drugs, toxins) must be ruled out before declaration of brain death. A flat electroencephalogram is consistent with brain death. Transcranial Doppler and traditional or isotope angiography are used to confirm the clinical examination and lack of blood flow to the brain.
  3. Brain-dead patients may have intact spinal reflexes, so they may require neuromuscular blockade during organ procurement.
  4. Brain death is associated with hemodynamic instability, hormonal chaos, systemic inflammation, and oxidant stress, all of which may negatively impact donor organ function. After pituitary failure ensues, hormone therapy may help stabilize patients hemodynamically. Cardiac graft function is likely improved by donor hormone therapy (tri-iodothyronine, methylprednisolone, desmopressin, insulin).
  5. The mainstay of donor management is maintenance of euvolemia, so central venous pressure (CVP)

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monitoring is standard. (CVP is maintained at 6 to 12 mm Hg.)

  1. Efforts should be made to maintain serum sodium below 155 mmol/L. Packed cells are used to maintain hematocrit of 30%, and fresh-frozen plasma (FFP) is used to maintain the international normalized ratio (INR) below 1.5.
  2. The anesthesiologist is responsible for maintaining donor oxygenation, perfusion, and normothermia.
  3. Donor lungs are more susceptible to injury in brain-dead patients before procurement than are other organs, likely from contusion, aspiration, or edema with fluid resuscitation (Table 54-1). In selected recipients, these kinds of marginal donors can be used without increasing the incidence of primary graft dysfunction (PGD).
  4. Donation After Cardiac Death (DCD)
  5. The criteria for death of DCD donors (previously called non–heart-beating donors) are distinct from those of brain-dead donors. DCD donors typically have severe whole brain dysfunction but have electrical activity in the brain. Death is defined by cessation of circulation and respiration. Life support measures are used to control the timing of death and organ procurement to maximize the function of organs from these donors.
  6. Anesthesiologists do not necessarily have to be involved in DCD donor management. Circulation and respiration must be absent for 2 minutes before the start of organ recovery.

Table 54-1 Characteristics of the Ideal Deceased Lung Donor

Age younger than 55 years
ABO compatibility
Clear chest radiographs
PaO2 >300 on FIO2 1.0, PEEP 5 cm H2O
Tobacco history <20 pack-years
Absence of chest trauma
No evidence of aspiration or sepsis
Negative sputum Gram stain
Absence of purulent secretions at bronchoscopy

PEEP = positive end-expiratory pressure.

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  1. Living Kidney Donors

Safety and comfort are the primary considerations in the care of living donors. Open nephrectomy is being progressively replaced by laparoscopic donor nephrectomy.

  1. Both anesthetics and insufflation of the peritoneum with CO2decrease renal blood flow, so fluid repletion is important to maintaining renal perfusion.
  2. Nitrous oxide is contraindicated for laparoscopic donor nephrectomy because bowel distention can impede surgery.

III. Living Liver Donors

Left lobe liver donation is usually done in the context of parent-to-child donation. Donor right lobectomy is needed for adult-to-adult liver transplantation.

  1. Large liver resections may require virtually complete hepatic venous exclusion (cross-clamping of the hepatic pedicle, usually without cava clamping).
  2. Transesophageal echocardiography is ideal and may obviate placement of central lines.
  3. INR increases significantly after right lobe surgery, peaking a few days after surgery along with a decrease in platelet counts, just when an epidural catheter for postoperative pain management is usually removed.
  4. Immunosuppressive Drugs (Table 54-2)

Pharmacologic suppression of the immune response to allografts is associated with major side effects (Table 54-3). Immune-suppressed patients coming to the operating room deserve special attention to sterile technique and

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maintenance of antibiotic, antifungal, and antiviral regimens during the perioperative period.

Table 54-2 Immunosuppressive Drugs

Calcineurin inhibitors (cyclosporine, tacrolimus)
Corticosteroids (maintenance immunosuppression)
Monoclonal and polyclonal antibodies
mTOR inhibitors
Azathioprine
Mycophenolate mofetil

mTOR = mammalian target of rapamycin.

Table 54-3 Complications of Chronic Immune Suppression

System

Complication

Central nervous system

Lowered seizure threshold

Cardiovascular

Hypertension
Hyperlipidemia
Atherosclerosis

Renal and electrolyte

Decreased GFR
Hyperkalemia
Hypomagnesemia

Hematologic and immune

Increased risk of infections
Increased risk of malignancy
Pancytopenia
Diabetes

Endocrine or other

Osteoporosis
Poor wound healing

GFR = glomerular filtration rate.

  1. Renal Transplantation
  2. Preoperative Considerations.An enormous variety of diseases are treated with renal transplants (Table 54-4). About half the mortality of patients on dialysis is

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caused by heart failure. Hypercoagulable states are common in patients with renal disease. All solid organ transplant patients are screened for tumors (mammography, Pap test, colonoscopy, prostate specific antigen) and infection (dental evaluation, viral serologies).

Table 54-4 Common Causes of Renal Failure in Adult Renal Transplant Recipients

Diagnosis

% of Patients on List

Type 2 diabetes

21.7

Hypertensive nephrosclerosis

19.4

Retransplant or graft failure

8.7

Polycystic kidney disease

5.9

Type 1 diabetes

5.0

Focal glomerular sclerosis

4.7

Systemic lupus erythematosus

2.9

Chronic glomerulonephritis

2.9

Malignant hypertension

2.6

IgA nephropathy

2.4

  1. Intraoperative Protocols.Renal transplantation is generally done under general anesthesia. Before incision, antibiotics are given. A central venous catheter (usually triple lumen) is placed for CVP monitoring and drug administration, and a bladder catheter is placed.
  2. The major anesthetic consideration is maintenance of renal blood flow.
  3. Typical hemodynamic goals during renal transplant surgery are systolic pressure above 90 mm Hg, mean systemic pressure above 60 mm Hg, and CVP above 10 mm.
  4. After the first anastomosis is started, a diuresis is initiated (mannitol and furosemide are often both given). Dopamine does not reliably improve renal function in this setting.
  5. Liver Transplantation
  6. Preoperative Considerations.Patients with end-stage liver disease (ESLD) have multisystem dysfunction with cardiac, pulmonary, and renal compromise because of their liver disease, and multiorgan dysfunction at the time of transplantation is common (Table 54-5).
  7. Patients with ESLD generally have very low systemic vascular resistance, high cardiac index, and increased mixed venous oxygen saturation. Echocardiography is also used to screen patients for portopulmonary hypertension and intracardiac shunts.
  8. There is general agreement that mean pulmonary artery pressure above 50 mm Hg is an absolute contraindication to liver transplantation.
  9. Intraoperative Procedures
  10. Rapid sequence induction of general anesthesia is indicated because patients with ESLD often have gastroparesis in addition to increased intra-abdominal pressure from ascites.
  11. A rapid infusion system with the ability to deliver at least 500 mL/min of warmed blood is primed and

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in the room. Normothermia, which is essential for optimal hemostasis, is maintained with fluid warmers and convective air blankets over the legs and upper body.

Table 54-5 Multisystem Complications of End-Stage Liver Disease

System

Consequences

Central Nervous System

Fatigue

Encephalopathy (confusion to coma)

Blood–brain barrier disruption and intracranial hypertension (acute liver failure)

Pulmonary

Hypoxemia or hepatopulmonary syndrome

Respiratory alkalosis

Pulmonary hypertension

Reduced right heart function

Cardiovascular

Reduced SVR

Hyperdynamic circulation

Diastolic dysfunction
Prolonged QT interval
Blunted responses to inotropes
Blunted responses to vasopressors
Diabetes
Gastrointestinal
GI bleeding from varices
Ascites
Delayed gastric emptying
Hematologic

Decreased synthesis of clotting factors
Hypersplenism (pancytopenia)
Impaired fibrinolytic mechanisms

Risk of massive surgical bleeding

Renal

Hepatorenal syndrome
Hyponatremia

Impaired renal excretion of drugs

Endocrine
Glucose intolerance

Osteoporosis

Fracture susceptibility

Nutritional or metabolic

Muscle wasting and weakness

Other
Poor skin integrity
Increased volume of distribution for drugs

Decreased citrate metabolism

Calcium requirement with rapid FFP infusion

FFP = fresh-frozen plasma; GI = gastrointestinal; SVR = systemic vascular resistance.

  1. Liver transplantation is traditionally described in three phases: the dissection, anhepatic, and neohepatic phases, with reperfusion of the graft marking the start of the neohepatic phase.
  2. Coagulation Management
  3. FFP is used to maintain INR at 1.5 or below in patients with anticipated or ongoing bleeding.
  4. Maintaining fibrinogen above 150 mg/dL with cryoprecipitate is critical for hemostasis.
  5. Perioperative renal dysfunction, with hypovolemia and anesthetic-induced reduction of renal blood flow, is a major challenge in liver transplantation. Hepatorenal syndrome is a functional renal disorder that is associated with liver disease.
  6. Pediatric Liver Transplantation.Indications for pediatric liver transplantation differ considerably from those in adults, with biliary atresia the most common indication. Portopulmonary hypertension is rare in children, but biliary atresia is associated with atrial septal defects and situs inversus.
  7. Acute Liver Failure.Anesthetic considerations for both adults and children with acute liver failure are focused on protection of the brain. Patients with acute or fulminant hepatic failure may have a rapidly progressive course of elevated intracranial pressure (ICP), leading to herniation and death. Mannitol is used for osmotherapy to an end point of 310 mOsm/L, and hyperventilation is commonly used to manage ICP. Hypothermia is also considered brain protective in patients with acute liver failure.

VII. Pancreas and Islet Transplantation

  1. The majority of pancreas transplants (~75%) are done as simultaneous pancreas and kidney transplants from a single deceased donor.
  2. The major difference between pancreas transplantation and other procedures is that strict attention to control of blood glucose is indicated to protect newly transplanted β cells from hyperglycemic damage.

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VIII. Small Bowel and Multivisceral Transplantation

  1. In general, intestinal transplantation should only be considered in patients with life-threatening complications from intestinal failure.
  2. For anesthesiologists, a major hurdle for these transplants is line placement that is adequate for transfusion of blood products and fluids, which may be substantial during these long procedures. Ultrasound devices are helpful in identifying the known patent vessels for cannulation, but surgical cutdowns for venous access may be necessary.
  3. Nitrous oxide, as in liver transplantation, should be avoided.
  4. Common complications of intestinal failure include dehydration and electrolyte abnormalities, gastric acid hypersecretion, pancreatic insufficiency, bone disease, and total parenteral nutrition–induced liver failure.
  5. Lung Transplantation

Chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, and α1-antitrypsin deficiency are the most common indications for lung transplantation. Surgical options for lung transplantation are single-lung transplant, en bloc double-lung transplants, sequential double-lung transplants, and heart–lung transplantation.

  1. Recipient Selection(Table 54-6). Pulmonary function tests, left and right heart catheterization, and transthoracic echocardiography are routinely used for evaluating recipients.
  2. Preanesthetic Considerations
  3. By definition, lung transplant candidates have poor pulmonary status and are frequently receiving multiple therapies, including oxygen, inhaled bronchodilators, steroids, and vasodilators.
  4. After determining oxygen saturation, slow, incremental dosing of a short-acting benzodiazepine (0.25–1.0 mg midazolam) is used for anxiolysis.
  5. Intraoperative Management: Single-Lung Transplantation
  6. Lung transplant recipients tend to be chronically intravascularly volume depleted, and anesthetic induction can be associated with hypotension.

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Table 54-6 Lung Recipient Selection Guidelines

General Indications
End-stage lung disease
Failed maximal medical treatment of lung disease
Age within limits for planned transplant
Life expectancy <2–3 yr
Ability to walk and undergo rehabilitation
Sound nutritional status (70%–130% of ideal body weight)
Stable psychosocial profile
No significant comorbid disease
Disease-Specific Indications
COPD
   FEV1 <25% of predicted value after bronchodilators
   PaCO2 > 55 mm Hg
   Pulmonary hypertension (especially with cor pulmonale)
   Chronic oxygen therapy
Cystic fibrosis
   FEV1 <30% predicted
   Hypoxemia, hypercapnia, or rapidly declining lung function
   Weight loss and hemoptysis
   Frequent exacerbations, especially in young women
   Absence of antibiotic-resistant organisms
   Idiopathic pulmonary fibrosis
   Vital capacity <60%–65% of predicted
   Resting hypoxemia
   Progression of disease despite therapy (steroids)
Pulmonary hypertension
   NYHA functional status class III or IV despite prostacyclin therapy
   Mean right atrial pressure <15 mm Hg
   Mean pulmonary artery pressure <55 mm Hg
   Cardiac index <2 L/min per m2
Eisenmenger's syndrome
   NYHA class III or IV despite optimal therapy
Pediatric
   NYHA class III or IV
   Disease unresponsive to maximal therapy
   Cor pulmonale, cyanosis, low cardiac output

COPD = chronic obstructive pulmonary disease; FEV1 = forced expiratory volume in 1 second; NYHA = New York Heart Association.

  1. Nitrous oxide is rarely an anesthetic option because of bullous emphysematous disease, pulmonary hypertension, or intraoperative hypoxemia.
  2. Lung isolation, preferably with a double-lumen endotracheal tube, is necessary for single and bilateral sequential lung transplantation.

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  1. Lung recipients are susceptible to development of pulmonary hypertension and right ventricular dysfunction or failure during one-lung ventilation. Vasodilator or inotropic support may be required. Inhaled nitric oxide is another option for improving respiratory and right ventricular status.
  2. During one-lung ventilation, hypoxemia is common.
  3. Double-Lung Transplantation
  4. En bloc double-lung transplant requires cardiopulmonary bypass (CPB), and a single-lumen endotracheal tube is sufficient. Bilateral sequential transplant is now the preferred procedure because a tracheal anastomosis is unnecessary and surgical bleeding is less.
  5. The clamshell incision is extensive and can cause significant postoperative pain. Thoracic epidurals are often used to provide pain relief.
  6. Pediatric Lung Transplantation.The most common diagnoses are cystic fibrosis, congenital heart disease, and primary pulmonary hypertension. Most pediatric patients receive double-lung transplantation with CPB.
  7. Primary Graft Dysfunction (PGD)
  8. The cause of PGD is not yet clearly defined and is certainly multifactorial. The diagnosis is not applicable for dysfunction starting more than 72 hours after reperfusion.
  9. Anesthetic management does not appear to be a risk factor for PGD.
  10. Severe, life-threatening PGD has been successfully managed with extracorporeal membrane oxygenation.
  11. Inhaled nitric oxideis used to decrease pulmonary vascular resistance and improve oxygenation.
  12. Heart Transplantation

Overall 1-year survival has improved from 74% in the early 1980s to 87% currently.

  1. Left Ventricular Assist Devices (LVADs)
  2. LVADs differ with respect to flow pattern (pulsatile or nonpulsatile), requirements for anticoagulation (none, aspirin, coumadin), filling pattern (fill-to-empty or various other modes), power source (battery or alternating current), potential for electromagnetic interference, and impact of arrhythmias and defibrillation on the device.

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  1. Failure to maintain adequate preload or normal afterload results in decreased LVAD flow and hypotension from low functional cardiac output.
  2. Patients presenting for initial device placement are in various stages of decompensated heart failure and need invasive monitoring with an arterial line and either a pulmonary artery catheter or central venous line.
  3. Recipient Selection
  4. Medical therapy for patients with congestive heart failure has improved dramatically over the past decade. Pharmacologic options now include angiotensin-converting enzyme inhibitors, beta-blockers, diuretics, and digoxin.
  5. Pulmonary hypertension is associated with increased perioperative mortality, so severe, irreversible pulmonary hypertension is a contraindication to transplant.
  6. Preanesthetic Considerations
  7. Donor heart function worsens with donor cold ischemia times above 6 hours. Preoperative evaluation and preparation of the patient must be expeditious.
  8. Induction of anesthesia and surgical incision of the recipient begin when the donor team has evaluated the donor and made the final determination that the organ is acceptable. There must be strict attention to sterility. Inotropes (dobutamine, vasopressin) should be readily available before induction (Table 54-7).
  9. Intraoperative Management.Anesthetic induction in patients with poor ventricular function can be complicated by hemodynamic instability. High-dose opioid techniques have been used for induction and management of cardiac transplant patients with good results.
  10. Managment of Transplant Patients for Nontransplant Surgery
  11. For solid organ recipients, evaluation of patients is centered on function of the grafted organ.
  12. A major consideration for renal transplant recipients is maintenance of renal perfusion with adequate volume replacement. Thus, CVP monitoring is useful for preventing prerenal damage to transplanted kidneys, but

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central venous lines must be placed using strict aseptic technique.

Table 54-7 Effect of Denervation on Cardiac Pharmacology

Substance

Recipient

Mechanism

Digitalis

Normal increase of contractility

Direct myocardial effect

Minimal effect on atrioventricular node

Denervation

Atropine

None

Denervation

Adrenaline

Increased contractility
Increased chronotropy

Denervation hypersensitivity

Noradrenaline

Increased contractility

Denervation

Increased chronotropy

No neuronal uptake

Isoproterenol

Normal increase in contractility
Normal increase in chronotropy

Quinidine

No vagolytic effect

Denervation

Verapamil

Atrioventricular block

Direct effect

Nifedipine

No reflex tachycardia

Denervation

Hydralazine

No reflex tachycardia

Denervation

Beta-blocker

Increased antagonist effect

Denervation

  1. For all transplant recipients, antibiotic, antiviral, antifungal, and immune suppression regimens should be disrupted as little as possible in the perioperative period.
  2. Transplanted hearts are denervated and cannot respond to indirect-acting agents, such as ephedrine and even dopamine. Dobutamine can also be helpful, but norepinephrine and epinephrine should be reserved for refractory cardiogenic shock.

Editors: Barash, Paul G.; Cullen, Bruce F.; Stoelting, Robert K.; Cahalan, Michael K.; Stock, M. Christine

Title: Handbook of Clinical Anesthesia, 6th Edition

Copyright ©2009 Lippincott Williams & Wilkins

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