Anesthesia for Transplant Surgery

Anatomy and Physiology

The kidney is heterotopically transplanted into the left or right iliac fossa. Arterial blood is supplied through the iliac artery, and venous drainage occurs via the iliac vein. Over time, particularly during episodes of rejection, fibrosis can increase, leading to declining kidney function; the artery may become stiffer and more prone to stenosis, with rising vascular resistance.[1][2] 

A pancreas transplant is rarely performed alone and is usually combined with a kidney transplant in a procedure known as a simultaneous pancreas-kidney transplant. The most common indication is diabetes mellitus, followed by cystic fibrosis. Diabetes mellitus often leads to kidney failure, which is why indications for pancreas transplant typically include those for kidney transplant as well. The pancreas is usually transplanted on the opposite side of the kidney and connected to the iliac artery. Venous drainage occurs either through the iliac vein or the portal vein. The pancreatic duct is connected to the ileum, usually via a Roux-en-Y loop.

In an orthotopic liver transplant, the graft is anastomosed to the same site in the right upper abdomen after removal of the diseased organ. For subsequent upper abdominal surgical procedures, any existing extraanatomical vascular reconstructions or biliodigestive anastomoses increase the risk of bleeding and organ injury. Portal venous resistance decreases significantly immediately after liver transplant and continues to decline in the first few years.[3] Because portal hypertension underlies many anesthesia-related comorbidities, including esophageal varices and ascites, these conditions typically resolve as portal hypertension decreases. The hyperdynamic circulatory state also normalizes after transplant.[4]

Indications

The primary indication for organ transplant is irreversible organ failure, which may result from intrinsic organ disease or secondary systemic disease. Various bridge therapies are used to maintain organ function until a transplant is achieved.

Kidney Transplant

A patient becomes a candidate for a kidney transplant when there is an irreversible decrease in glomerular filtration rate of less than 20 mL/min/1.73 m².[5] See Table 1 for the causes of kidney failure requiring a kidney transplant.

Table 1. Causes of Kidney Failure

In the case of a living donor transplant, the recipient can be in the early stages of end-stage renal disease (ESRD) and not require dialysis. Living donor kidney transplants have shown better graft survival and function.  

Pancreas Transplant   

The causes of pancreatic failure are diabetes mellitus type 1 and 2, chronic pancreatitis, pancreatic cancer, biliary duct cancer, and graft failure. Pancreas transplant can be performed alone, simultaneously with a kidney transplant, or after a kidney transplant.    

Liver Transplant  

Table 2 describes the causes of liver failure requiring a transplant.

Table 2. Causes of Liver Failure 

The Model for End-Stage Liver Disease (MELD) score determines transplant priority. Several exceptions to the standard MELD score exist, including hepatocellular carcinoma, hepatopulmonary syndrome, portopulmonary syndrome, familial amyloid polyneuropathy, cystic fibrosis, hilar cholangiocarcinoma, and acute liver failure with UNOS status 1A or 1B.[6] For hepatocellular carcinoma, the Milan criteria are used, which include a single hepatic lesion smaller than 5 cm or 2 to 3 lesions, each 1 to 3 cm.[7]

Contraindications

The major contraindications for organ transplant are active infection, active malignant neoplasms, active illicit drug use, reversible organ failure, uncontrolled psychiatric disorder, noncompliance with treatment, and severe systemic conditions with poor graft or patient survival. Malignant neoplasms and infection should be treated prior to organ transplant. Graft survival requires consistent follow-up with the transplant team, regular clinic visits, laboratory monitoring, and adherence to transplant medications. Careful candidate selection is therefore essential.[8][9]

Equipment

Standard American Society of Anesthesiologists intraoperative monitoring includes a 5-lead electrocardiogram, pulse oximeter, noninvasive blood pressure monitor, and temperature probe. In addition to standard monitoring, invasive and noninvasive devices are used during transplant surgical procedures, given the major hemodynamic variation anticipated. Invasive arterial blood pressure monitoring provides real-time values and is particularly important during a liver transplant, when severe hemodynamic fluctuations are common.

Stroke volume variation and pulse pressure variation are dynamic metrics that help assess volume status. Depending on institutional protocol, 1 or 2 arterial lines may be placed (one radial and one brachial or femoral). A central line is inserted for central venous pressure monitoring and for the administration of vasopressors and inotropes (see Table 3). In some cases, when there is severe pulmonary hypertension, portopulmonary shunts, or diminished right heart function, a pulmonary artery catheter is inserted to monitor pulmonary pressures. The transesophageal echocardiogram is used in some liver transplant cases to monitor right and left heart function, assess the patient's volume status, detect cardiac clots early, and guide placement of a pulmonary artery catheter. Transesophageal echocardiography is contraindicated in grade 3 and 4 esophageal varices. 

Table 3. Vasopressors and Ionotropes Used in Transplant Procedures 

HTN, hypertension; kg, kilogram; MAP, mean arterial pressure; N/A, not applicable; PDE-3, phosphodiesterase-3; U, units

Various invasive and noninvasive methods have been developed to measure cardiac output, including arterial waveform analysis, thoracic bioimpedance and bioreactance, aortic Doppler, and point-of-care echocardiography. While arterial pulse waveform analysis requires an arterial catheter, the other techniques are noninvasive but rely on complex algorithms or skilled operators. Their accuracy compared to standard echocardiography or pulmonary artery catheter measurements of cardiac output may vary.[10][11][12]

Intraoperative arterial blood gas analysis and thromboelastographic studies are valuable during liver transplant surgical procedures. Arterial blood gas analysis provides information on acid-base balance and electrolytes, while thromboelastography helps characterize the coagulation cascade and identify which hemostatic components contribute to coagulopathy, guiding targeted repletion. Neuromuscular block monitoring is performed using train-of-four studies, which also guide reversal and extubation, particularly in kidney and liver transplantation, where drug metabolism is slowed by impaired organ function.

The bispectral index helps reduce awareness during anesthesia and helps titrate drug dosing effectively. Neuromonitoring with cerebral oximetry using near-infrared spectroscopy is not universally used; however, some centers employ this technology to detect impaired cerebral autoregulation and monitor cerebral deoxygenation during the anhepatic phase and hyperoxygenation during the reperfusion phase of liver transplant.[13] Jugular venous oxygen saturation is used to monitor cerebral blood flow and oxygen consumption, particularly during the anhepatic and neohepatic phases, when significant fluctuations in cardiac output can alter cerebral perfusion.[14][15][16][17]

Preparation

Preoperative evaluation and optimization should begin as soon as an individual becomes a candidate for an organ transplant. Early evaluation plays a critical role in minimizing perioperative complications and improving graft and recipient survival. Recipients are screened for malignant neoplasm, active infection, and viral infections, including human immunodeficiency virus, hepatitis virus panel, Epstein-Barr virus, and cytomegalovirus. Additional testing is guided by comorbidities, including coronary artery disease, peripheral artery disease, and cerebrovascular disease.

Documenting allergies, prior solid-organ transplant, prior blood transfusions, and previous pregnancies is essential, as this information helps determine antibody load and guide the immunosuppression regimen. Rabbit allergy is important to note because antithymocyte globulin is derived from rabbit serum. Additional testing is performed per institutional protocol, and repeat evaluation is required every 2 years after the initial assessment, or sooner if the clinical situation changes. 

Candidates requiring coronary revascularization require interdisciplinary team evaluation to determine the appropriate timing and type of intervention. The minimum duration of dual antiplatelet therapy is 4 weeks for balloon angioplasty, 3 months for a bare-metal stent, and 6 to 12 months for a drug-eluting stent. No formal guidelines exist for pulmonary function testing; however, individuals with uncontrolled chronic obstructive pulmonary disease, asthma, or interstitial lung disease should not undergo organ transplant. Patients undergoing pancreas transplant tend to be younger with fewer comorbidities but may be at greater risk for microvascular and macrovascular complications related to diabetes mellitus.[18][19][20][21][22]

When a candidate remains eligible for transplant, and an organ becomes available, the surgical procedure is scheduled. A thorough airway examination is required before the surgical procedure, along with a review of bleeding or clotting disorders, prior exposure to anesthesia, the type of anesthesia received, any associated complications, and a family history of anesthesia-related adverse events. Drug allergies are an important component of the preoperative evaluation to prevent intraoperative adverse reactions.

The anesthesiologist should document consent for blood and blood product transfusion, history of prior transfusions, and any prior adverse transfusion reactions. Individuals with a permanent pacemaker or implantable cardioverter-defibrillator require device interrogation by a company representative before the surgical procedure; qualified personnel must be present throughout the procedure to manage the device and restore baseline settings upon completion. Thorough preoperative preparation with attention to these details can minimize anesthesia-related complications.

The following tests are performed on the day of surgery:

• Complete blood count with differential  
• Complete metabolic panel 
• Coagulation panel 
• Blood group and human leukocyte antigen crossmatch and typing 
• 12-lead echocardiogram
• Chest radiograph
• Covid nasopharyngeal antigen and antibody testing 

Technique or Treatment

Antibiotics and immunosuppressive regimens, per transplant clinician recommendations, are administered on the day of the surgical procedure. The surgeon will perform back-table preparation of the donor organ.   

Kidney Transplant

Dialysis   

The patient may or may not be dialysis-dependent. An anesthesiologist should evaluate the patient's volume status, electrolyte levels, and degree of uremia on the day of the surgical procedure. Historically, hemodialysis was avoided in the 24 hours before transplant to reduce circulating heparin; however, with advances in anesthesia care, point-of-care diagnostics, and technique, this restriction is no longer required.[23][24][25]

Intraoperative management

Normothermia should be maintained, the individual positioned appropriately, and dialysis access sites secured. Nephrotoxic drugs and opioids with renally excreted active metabolites, including morphine, meperidine, and codeine, are avoided. Succinylcholine can increase serum potassium levels, which may be detrimental in individuals with ESRD.

Cisatracurium, metabolized by Hofmann elimination, can be used safely in renal failure. Laudanosine, a breakdown product of both atracurium and cisatracurium, is renally eliminated; because cisatracurium is more potent than atracurium, the amount of laudanosine generated is substantially lower and below the toxic threshold. Rocuronium is partially renally excreted. Sugammadex is renally cleared; however, complete reversal has been demonstrated in renal failure, and although clearance of the sugammadex-rocuronium complex is prolonged, no rebound muscle weakness has been observed.[26][27][28]

Oxygen and air, or oxygen and nitrous oxide, are routinely used with inhalational agents. Sevoflurane administration can lead to accumulation of inorganic fluoride ions and compound A in individuals with renal insufficiency; however, the Food and Drug Administration has approved sevoflurane use at fresh gas flows greater than 1 L/min. Isoflurane and desflurane are acceptable alternatives.

Fluid management

Volume replacement is guided by preoperative volume status. Acetated or lactated solutions may increase potassium levels in individuals with ESRD. Normal saline causes hyperchloremic acidosis, prolonging acid-base normalization. Adequate graft perfusion is essential to prevent delayed graft function or ischemia-reperfusion injury; the autoregulatory mechanism is absent in the transplanted kidney.

Colloids are not the preferred choice for volume replacement. Dynamic monitoring with stroke volume variation and pulse pressure variation helps guide volume resuscitation. Vasopressors such as norepinephrine, which have both α-adrenergic and β-adrenergic activity, have been shown to reduce elevations in renal resistive indices. Low-dose dopamine was previously favored but has been shown to be harmful to renal grafts and is no longer used.[29]

Immunosuppression

Mycophenolate and methylprednisolone are administered before the procedure. Thymoglobulin is administered intraoperatively, with the infusion rate adjusted according to blood pressure. If the initial dose causes hypotension, the rate is reduced by half.    

Pancreas Transplant

Thorough airway examination is essential in individuals with diabetes mellitus, given the increased incidence of atlantoaxial joint stiffness. Pancreas transplant is performed under general anesthesia with an induction agent, a muscle relaxant, and opioids. When cardiovascular instability is a concern, etomidate is preferred for induction. Individuals with diabetes mellitus may develop gastroparesis; when present, rapid-sequence induction is performed.

The transplanted pancreas typically begins functioning within 5 minutes of reperfusion, requiring strict glucose monitoring to prevent pancreatic cell dysfunction. Glucose levels should be checked every 15 minutes for the first hour, then every 30 minutes thereafter. No major fluid shifts are anticipated during a pancreas transplant. Blood pressure targets should be maintained slightly above baseline after transplant to ensure adequate graft perfusion.[30][31]

Liver Transplant  

Induction

Rapid-sequence induction is preferred when aspiration is a concern, particularly in individuals who are not fasting or who have gastroparesis or ascites. The pharmacodynamics and pharmacokinetics of drugs are altered in liver transplant recipients because of decreased serum albumin, increased volume of distribution, and changes in hepatic drug metabolism. Induction agents must be selected carefully, as they affect systemic blood pressure and hepatic blood flow. Etomidate has been shown to decrease hepatic blood flow with unpredictable clinical recovery. Propofol is a vasodilator associated with a moderate decrease in hepatic blood flow.

Muscle relaxants

Atracurium and cisatracurium are the preferred muscle relaxants, as both are metabolized via Hofmann degradation. Rocuronium may be used if sugammadex is available.  

Inhalational agents

Desflurane and sevoflurane do not adversely affect hepatic blood flow.

Vasopressors and inotropes

Vasopressors and inotropes should be immediately available, as hemodynamic fluctuations are anticipated. Contributing factors include coagulopathy, extensive blood loss, decreased preload, third-space fluid loss, and reperfusion syndrome. Norepinephrine, epinephrine, and dopamine are used as first-line agents; vasopressin is reserved for refractory hypotension.

Intravenous volume resuscitation

Albumin synthesis is impaired in end-stage liver disease. Albumin administration has been shown to reduce mortality, crystalloid requirements, the need for vasoactive drugs, the incidence of pulmonary edema, and the incidence of postreperfusion syndrome. Hydroxyethyl starch is associated with increased coagulopathy, decreased platelet aggregation, and reduced factor VIII levels.

Isotonic potassium-containing crystalloid is preferred. Large-volume administration of normal saline can cause a rapid rise in serum sodium, increasing the risk of central pontine myelinolysis. Lactated Ringer solution in the setting of liver failure can cause lactate accumulation and lactic acidosis. Cell savers may be used for autologous blood transfusion; however, their use is contraindicated in the setting of infection or malignant neoplasm.[32][33]

Coagulation testing

Viscoelastic point-of-care tests, such as thromboelastography (TEG) and its modified form, rotational thromboelastometry (ROTEM), are widely used in many centers to assess global coagulation status during liver transplant and other complex procedures. Table 4 presents viscoelastic thresholds from TEG and ROTEM to guide targeted transfusion during liver transplant. These parameter interpretations should be used alongside standard coagulation tests, the presence of active bleeding, and the surgical phase when making clinical decisions.

Table 4. Viscoelastic Thresholds for Targeted Transfusion

Phases in liver transplantation

Each phase is associated with distinct pathophysiological changes that must be recognized and anticipated with a management plan in place.  

Prehepatic phase

The prehepatic phase begins at skin incision and ends with clamping of the inferior vena cava. Hypotension is expected during this phase and may result from sudden loss of ascitic fluid, portal hypertension, portopulmonary shunts, or surgical bleeding compounded by the coagulopathy of end-stage liver disease. Judicious fluid administration, guided by thromboelastography, is essential.

Excessive volume resuscitation must be avoided, as it can lead to dilutional coagulopathy and thrombocytopenia. Octreotide infusion may be used in the setting of portal hypertension and requires careful monitoring; it reduces the need for blood transfusion and can improve renal function. When hypotension persists despite these measures, venovenous bypass should be considered.[34][35]

Anhepatic phase

The anhepatic phase begins with clamping of hepatic venous outflow and ends when vascular anastomosis is achieved. Hypotension is common during this phase, resulting from decreased preload and reduced cardiac output. Refractory hypotension warrants consideration of a portosystemic or venovenous shunt.

Ensuring adequate cerebral blood flow is essential during this stage. Accumulation of lactate, citrate, and other metabolites leads to acidosis, hypocalcemia, and hyperkalemia. Hyperkalemia is managed with insulin and dextrose, sodium bicarbonate, loop diuretics, and tromethamine; renal replacement therapy should be considered as a last resort.

Coagulopathy is not uncommon during the anhepatic phase; TEG findings will guide correction, which should be pursued only when clinically indicated, as spontaneous correction occurs during the neohepatic phase. In recipients with hepatitis B infection, hepatitis B hyperimmune globulin is administered during this stage, and clinicians should monitor for allergic reactions.[36][37]

Neohepatic phase

The neohepatic phase begins with liver reperfusion and ends when blood flow to the portal vein and inferior vena cava is restored. Maintaining a mean arterial pressure between 80 and 100 mm Hg before revascularization is preferable. Clinicians must monitor for postreperfusion syndrome, worsening pulmonary hypertension, right heart failure, and malignant arrhythmia.

Volume resuscitation, autologous blood transfusion (preferred over packed red blood cells because of lower potassium content), and inotropes are administered as clinically indicated. Reperfusion causes a sudden release of metabolites and vasodilatory substances, which can produce a precipitous fall in blood pressure and malignant arrhythmias. Intravenous calcium chloride helps stabilize the cardiac membrane in cases of hyperkalemia, which can cause electrocardiographic changes.

In the event of cardiac arrest, a diaphragmatic incision should be made and internal cardiac massage performed. Transthoracic echocardiography can assist in assessing volume status, detecting cardiac thrombi, and evaluating cardiac function. When cardiac thrombi are detected, and pulmonary thromboembolism is a concern, heparin and tissue plasminogen activator are administered.[38][39]

Pain management

Postoperative analgesia is usually managed with fentanyl or hydromorphone delivered through patient-controlled analgesia without a background infusion. Meperidine and morphine are generally avoided because of the risk of respiratory depression, and nonsteroidal anti-inflammatory drugs are not used because of potential renal toxicity. Continuous wound infiltration systems may also be used by the surgical team to supplement pain control.

Regional Anesthesia

The use of ultrasonography-guided regional anesthesia has expanded substantially over the past decade, supported by a growing body of evidence demonstrating its safety and effectiveness. Applications in transplant surgery are increasing, with multiple techniques proving feasible across various procedures. Although formal data on practice patterns are limited, adoption appears to be rising, particularly with the integration of enhanced recovery after surgery (ERAS) protocols.[40]

Renal transplant

Regional anesthesia is strongly supported in kidney transplant and donor nephrectomy, with substantial evidence demonstrating improved analgesia and reduced opioid requirements. Thoracic epidurals, transversus abdominis plane (TAP) blocks, and quadratus lumborum blocks are most commonly used. TAP blocks are widely incorporated into ERAS pathways because of their safety profile and ease of use. No single technique has demonstrated clear superiority, and selection is often individualized.

Liver transplant

Evidence for regional anesthesia in liver transplant is more limited, largely because of concerns regarding coagulopathy and hemodynamic instability. Emerging data suggest that fascial plane blocks, including TAP blocks and erector spinae plane blocks, provide effective analgesia with a favorable safety profile, while thoracic epidural analgesia may benefit carefully selected individuals without significant coagulation abnormalities. Regional techniques can reduce opioid consumption and improve recovery without major reported complications.

Pancreas transplant

Data on regional anesthesia in pancreas transplant are relatively sparse, but available evidence supports its role in multimodal analgesia. Thoracic epidural, TAP, and rectus sheath blocks have been associated with improved pain control and reduced opioid use, with TAP blocks demonstrating a particularly favorable safety profile. Current evidence suggests comparable efficacy among techniques, with a growing preference for fascial plane blocks due to their lower complication risk.

Complications

During organ transplant surgical procedures, complications may be related to anesthetic agents, immunosuppression, organ dysfunction, acid-base and electrolyte imbalances, coagulopathy, and blood loss. These complications are further elaborated in the context of each transplant type.

Clinical Significance

Solid organ transplant involving the kidney, pancreas, and liver poses unique perioperative challenges. Thorough preoperative evaluation and preparation for anticipated intraoperative complications can improve outcomes in these complex surgical procedures.

Enhancing Healthcare Team Outcomes

A successful organ transplant requires an interdisciplinary team that encompasses UNOS and local organ procurement organizations, the organ transportation team, transplant anesthesiologists, transplant surgeons, operating room personnel, transplant pharmacists, transplant clinicians, radiologists, physical therapists, occupational therapists, nutritionists, social workers, and robust social support systems.[13]

Successful transplant surgery and survival of the graft involve tremendous coordination between the team members due to the complexity of care involved, extending beyond the perioperative period. If the patient requires coronary revascularization,  a cardiology consultant is required. The consultant will determine the time and type of intervention required.[20]

No formal guidelines exist for pulmonary function testing. However, individuals with uncontrolled chronic obstructive pulmonary disease, asthma, or interstitial lung disease should be evaluated by a pulmonologist before being considered for organ transplant. Hemodialysis can be performed within 24 hours before a kidney transplant without adversely affecting early graft function. Coordination with nephrology for dialysis evaluation is therefore recommended.[23]