Anesthesia for Abdominal Organ Transplantation

Indications for Kidney Transplantation

Kidney transplantation is indicated in patients with ESRD caused by any one of a variety of underlying conditions. Glomerular disease, congenital diseases, and polycystic kidney disease are common indications in younger patients. Nephropathies associated with hypertension and diabetes are the most common indications for kidney transplantation in the United States. Diabetes is the leading cause of ESRD in the United States, representing 36% of all waitlisted candidates in 2016 ( Fig. 60.5 ). Renal graft failure is an increasingly common indication for transplantation as well. In 2015, 16% of all waitlisted candidates in the United States were awaiting retransplantation and higher percentages have been reported in other countries.

Pathophysiology of End-Stage Renal Disease

ESRD refers to the final progression of CKD, when renal function is irreversibly impaired and the development of uremia is imminent. Essential functions of the kidney include regulation of the ionic composition of the plasma, maintenance of fluid volumes, elimination of nitrogenous wastes and drugs, synthesis of erythropoietin, and adjustment of plasma pH. Significant declines in glomerular filtration rate (GFR) and urine production occur when these critical functions are damaged, resulting in the clinical manifestations of uremia. After the development of ESRD, renal replacement therapy is required. ESRD has an effect on nearly every organ system, and it has a major impact on patient mortality despite chronic therapy including hemodialysis.

ESRD results in abnormalities of fluid balance and electrolytes. With the onset of uremia and oliguria, expansion of the extracellular fluid volume ensues, presenting with edema, hypertension, and signs and symptoms of volume overload. Disorders of sodium, calcium, magnesium, and phosphate can result in chronic changes in bone metabolism, hyperparathyroidism, and vascular calcifications. The development of hyperkalemia, with its effects on the myocardium, is the most critical electrolyte abnormality. Failure of the renal elimination of organic acids results in the development of an anion-gap metabolic acidosis.

ESRD has a significant effect on the cardiovascular system. Cardiovascular disease is the most common cause of morbidity and mortality in patients with ESRD, accounting for 35% to 40% of all deaths in patients receiving hemodialysis. As GFR decreases, the risk of cardiac mortality increases. ESRD increases the development of atherosclerosis and is a major risk factor for the development of ischemic vascular disease, which can affect the coronary, cerebrovascular, and peripheral vascular systems. The likelihood of CAD, which can present as angina, myocardial infarction, arrhythmia, or sudden cardiac death, may be even greater in patients with hypertension and diabetes. Hypertension may be the etiology of ESRD in nearly 30% of patients, or conversely, hypertension may result from hyperreninemia, hypervolemia, and renal vasculature changes associated with ESRD. Concentric left ventricular hypertrophy and diastolic dysfunction occur in the early stages of CKD, and are the two most common echocardiographic abnormalities in patients with ESRD. Patients with ESRD are at particular risk for diastolic congestive heart failure, especially in the setting of excessive intravascular volume. Heart failure owing to dilated cardiomyopathy with decreased systolic function can occur in patients with ESRD as well. The cardiorenal syndrome is defined by an interconnection between the renal and cardiac systems, where the decline of one organ influences the decline of the other. There is evidence that correction of renal function by renal transplantation can improve systolic dysfunction and reverse left ventricular dilation and hypertrophy. A variety of arrhythmias can occur in ESRD because of progression of cardiac disease, myocardial ischemia, or electrolyte disturbances. Atrial fibrillation occurs in up to 27% of patients on hemodialysis and is associated with an increased risk of stroke, heart failure, and hemodynamic disturbance. Stroke is of significant concern in ESRD patients with atrial fibrillation, as patients with ESRD have nearly a 50% increased risk of stroke compared to the general population. Clinical dilemmas are common regarding anticoagulation in patients with atrial fibrillation and ESRD. Pericardial disease is common in patients with uremia, manifesting as pericarditis or pericardial effusion.

Characteristic hematologic and hemostatic abnormalities occur with ESRD. Normochromic, normocytic anemia secondary to lack of erythropoietin is common and may be exacerbated by iron deficiency, chronic inflammation, and bone marrow fibrosis. Anemia decreases quality of life in ESRD and is associated with adverse cardiac outcomes. Erythropoiesis-stimulating drugs and iron are commonly prescribed for the treatment of uremic anemia, and hemoglobin levels of 11 to 12 gm/dL are typically achieved. ESRD is associated with abnormal hemostasis because of a broad spectrum of platelet function abnormalities including decreases in platelet activity, aggregation, and adhesiveness. Production of von Willebrand factor and factor VIII is decreased. Historically, renal failure patients were considered to be at an increased risk for bleeding. However, ESRD is also associated with a hypercoagulable state owing to a variety of complex hemostatic changes including increased fibrinogen levels, reduced antithrombin levels, acquired thrombophilic factors, and endothelial alterations. Clinically, the risk of venous thromboembolism appears to increase as renal function decreases; manifestations may include deep venous thrombosis/pulmonary embolism and thrombosis of arteriovenous fistulas and vascular access catheters. Many of the hematologic changes of hypercoagulability have been shown to resolve in patients with ESRD after kidney transplantation.

Gastrointestinal signs and symptoms of ESRD include nausea, vomiting, and abdominal pain. Patients with ESRD may have delayed gastric emptying, regardless of the timing of their last oral intake. Dyspepsia occurs in 50% to 70% of patients on hemodialysis; ESRD patients with symptomatic dyspepsia have been shown to have particularly prolonged gastric emptying times. The presence of diabetes and obesity may further impair gastric emptying.

Central nervous system and neuromuscular abnormalities can occur in ESRD secondary to retained nitrogenous molecules. These abnormalities range from mild changes in memory or attention to signs and symptoms of neuromuscular irritability. Severe neurologic manifestations of uremia with asterixis, seizures, and decreased mental status are rare with regular dialysis. Peripheral neuropathy is the most common neurologic manifestation of ESRD and is documented in up to 90% of dialysis patients. Autonomic dysfunction is also common, documented in up to 50% of dialysis patients. Autonomic neuropathy is implicated in ESRD patients with orthostatic hypotension, cardiac arrhythmias, and gastric dysmotility. Kidney transplantation is the most effective treatment for the neurologic manifestations of ESRD.

Anesthesia for Kidney Transplantation: Preoperative Evaluation

Before kidney transplantation, patients typically undergo a prolonged pretransplant evaluation by a multidisciplinary transplant committee to determine their fitness for transplantation and to assess for the likelihood of long-term survival following transplantation. In general, the preoperative evaluation of patients for kidney transplant should focus on the multiorgan manifestations of ESRD, with the goals of risk stratification and optimization of the medical status of the patient before transplant. Cadaveric kidney transplantation is an urgent procedure, because harvested organs tolerate a finite duration of cold ischemia of approximately 24 hours. Living donor kidney transplants are scheduled well in advance, allowing for a thorough preoperative assessment before surgery.

As discussed previously, the current demographic of kidney transplant patients has a frequent association with cardiac disease, which has a major effect on posttransplant outcome. As a result, preoperative cardiac evaluation is of critical importance in this patient group. Compared with the routine preoperative evaluation of surgery patients without cardiac disease, the renal transplant patient should be assessed to consider both short- and long-term cardiac outcomes. The goal of the preoperative cardiac evaluation is ultimately to decrease the morbidity and mortality associated with cardiovascular disease in kidney transplant candidates. Although decisions regarding candidacy in high-risk patients are usually made well before surgery, the anesthesiologist should be involved in the routine cardiac risk assessment of the kidney transplant patient before surgery. The major focus of the preoperative cardiovascular assessment in kidney transplant patients is to identify occult ischemic heart disease.

The 2014 American College of Cardiology/American Heart Association (ACC/AHA) Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery recommends a preoperative algorithm designed to assist in the risk stratification of surgical patients. The stepwise algorithm includes identification of known CAD or CAD risk factors, estimation of the perioperative risk for major adverse cardiac events based on combined clinical and surgical risk factors, and determination of functional capacity. The decision to proceed with surgery or to undergo further noninvasive ischemia testing is contingent on functional capacity, scored by metabolic equivalent tasks (METS). No further testing is recommended when functional status is considered moderate or good (more than 4-10 METS) or excellent (more than 10 METS). If functional status is less than 4 METS or cannot be assessed, further ischemia testing may be considered. The utility of published guidelines to detect patients with ischemic heart disease has been called into question in the kidney transplant population and, in contrast to the 2014 more general guidelines, in 2012, the AHA and the American College of Cardiology Foundation issued a scientific statement stating that the cardiac evaluation and management among kidney and liver transplantation patients should form the basis of the long-term evaluation of the transplant patient. Silent myocardial ischemia may occur more frequently in patients with ESRD than in the general population, making the detection of unstable coronary syndromes more difficult. One study reported that chest pain presenting at the time of acute myocardial infarction was less common in patients with ESRD requiring dialysis compared with patients not using dialysis (44% vs. 68%). Decreased functional status might not be a specific or sensitive indicator of cardiovascular risk in kidney transplant candidates, and many ESRD patients are unable to exercise secondary to deconditioning. One study of kidney transplant candidates examined the effectiveness of various guidelines to detect asymptomatic CAD. The authors determined that if the 2014 ACC/AHA guidelines had been strictly applied to this group of patients, only a small proportion of the candidates with documented myocardial ischemia on noninvasive testing would have been detected. Finally, renal insufficiency is itself a CAD risk factor. The unique characteristics of ESRD patients, along with discrepancies among published guidelines, has called into question the applicability of available recommendations regarding cardiac testing in the kidney transplant population.

Noninvasive testing methods for CAD have been well studied in the kidney transplant population, although most investigations consisted of small study populations. In studies that compared either dobutamine stress echocardiography (DSE) or myocardial perfusion imaging with angiography in patients with renal failure, both methods demonstrated decreased accuracy compared to their accuracy in nonrenal failure patients. The response to coronary vasodilators appears to be decreased in ESRD patients with diabetes; this may contribute to false negative myocardial perfusion testing results. Chronotropic incompetence may diminish the maximum heart rate response to dobutamine in patients with ESRD and left ventricular hypertrophy may limit detection of reversible wall motion abnormalities during echocardiographic stress testing. Although noninvasive testing appears to be less reliable in kidney transplant patients compared to the general population, ischemia detected on noninvasive testing correlates with adverse cardiac events and mortality in patients with ESRD and in kidney transplant patients. One metaanalysis that analyzed studies using either DSE or myocardial perfusion studies in patients with ESRD demonstrated that patients with inducible ischemia or fixed defects had a significantly increased risk of cardiac death compared with patients with normal tests.

Although many guidelines and consensus-based recommendations regarding preoperative cardiac risk assessment in kidney transplant candidates have been published, there is no validated standardized approach. A stepwise process including a comprehensive cardiovascular history and evaluation of signs and symptoms of advanced cardiac disease, assessment of functional status, and identification of risk factors should be reviewed.

A baseline electrocardiogram (ECG) is an appropriate initial screening test in most kidney transplant patients, especially in patients older than 40 years. ECG abnormalities associated with cardiac disease are common in patients with ESRD. A preoperative ECG should be obtained in patients with known CAD, peripheral vascular disease, and cardiac symptoms. Noninvasive testing may be considered in asymptomatic patients with multiple risk factors for CAD. The most recent consensus document published in 2012 by the ACC/AHA provides recommendations for preoperative cardiac testing in kidney transplant candidates. Noninvasive ischemia testing should be considered in candidates with three or more of the following risk factors: known cardiovascular disease, diabetes, dialysis for more than 1 year, age over 60 years, tobacco use, left ventricular hypertrophy, dyslipidemia, and hypertension. The authors also recommend that the decision to proceed with noninvasive testing based on the presence of the above risk factors should be made regardless of functional status in kidney transplant candidates.

Preoperative assessment of left and right ventricular function by echocardiography is an appropriate test in most kidney transplant candidates. The likelihood of structural cardiac abnormalities and the potential for left ventricular dysfunction in ESRD is significant, and transthoracic echocardiography provides detailed information regarding resting cardiac function and structure with minimal testing risk.

An increased prevalence of occult pulmonary hypertension, up to 40% reported in one series, occurs in patients receiving dialysis. The mechanism involves both uremia-induced pulmonary vasoconstriction and increased cardiac output secondary to an arteriovenous fistula. Pulmonary hypertension may be reversible after kidney transplantation. The identification of pulmonary hypertension is important because its presence in patients with ESRD is associated with decreased survival. Right heart catheterization may be indicated in patients with evidence of significant pulmonary hypertension by echocardiography.

Patients with cardiac conditions may remain on transplant lists for many years before undergoing transplantation. During this time, cardiac disease can progress. Although routine periodic noninvasive screening in asymptomatic patients awaiting transplant is not warranted, patients with known cardiac disease should undergo regular repeat cardiac assessments although the frequency of assessments has not been defined.

Cardiovascular medications should be reviewed during the preoperative evaluation in kidney transplant candidates, and the patient advised on which medications should be taken before surgery. Most patients with ESRD receive multiple medications for the chronic treatment of hypertension; however, the ideal combination of drugs is not clear. Strategies for the perioperative administration of antihypertensive blood pressure medications are important; however, the urgency of deceased-donor kidney transplantation often allows only the immediate preoperative administration of antihypertensive medications. The risks and benefits of initiating or maintaining perioperative medical therapy in surgical patients have been extensively reviewed in the most recent ACC/AHA guideline; β-blockers, statins, α-2 agonists, calcium channel blockers, and angiotensin-converting enzyme inhibitors were included. There is limited information regarding perioperative antihypertensive therapy and its impact on survival in kidney transplant patients. In general, it is reasonable to apply current ACC/AHA recommendations regarding perioperative antihypertensive therapy in kidney transplant candidates.

As mentioned previously, there is an increasingly high prevalence of diabetes in the kidney transplant population. Perioperative hyperglycemia is associated with adverse outcomes in both diabetic and nondiabetic populations. Perioperative glycemic therapy should be initiated in patients with diabetes who are undergoing kidney transplant, yet a benefit from strict blood glucose control in the kidney transplant population has not been demonstrated. Studies demonstrating the risks of hypoglycemic episodes in protocols employing “tight” glucose control in surgical and intensive care unit (ICU) patients suggest that conventional glycemic targets may be safer during the perioperative period. Most medical society organizational guidelines recommend targeting blood glucose levels between 110 to 160 mg/dL and initiating insulin therapy for blood glucose levels over 180 mg/dL during the perioperative period.

Anesthesia for Kidney Transplant: Intraoperative Management

General anesthesia with endotracheal intubation is the preferred anesthetic method for kidney transplantation in most institutions. The goals of anesthesia are to facilitate an adequate depth of anesthesia while maintaining hemodynamic stability and to provide appropriate muscle relaxation to facilitate surgical conditions. As mentioned previously, patients with ESRD are considered at risk for aspiration of gastric contents secondary to the presence of uremic gastropathy and other conditions, such as obesity and diabetes. An oral nonparticulate antacid and intravenous administration of an H-2 blocker may be considered before induction of anesthesia. A rapid-sequence induction of anesthesia is the preferred method of induction for general anesthesia. Succinylcholine can be used safely in standard doses in patients with ESRD when potassium levels are within normal limits (usually < 5.5 mEq/L). Potassium transiently increases 0.5 to 1.0 mEq/L for 10 to 15 minutes before returning to baseline levels in patients with ESRD and those with normal renal function. A modified rapid-sequence induction using rocuronium 0.8 to 1.2 mg/kg intravenously may be a substitute for succinylcholine when hyperkalemia or other contraindications to succinylcholine exist. Rocuronium should be used in ESRD with caution as the duration of action is prolonged. A meta-analysis of 26 studies that compared the intubating conditions produced by succinylcholine and rocuronium found that intubation conditions were clinically similar when propofol was used as the induction anesthetic. The hemodynamic response to laryngoscopy may be accelerated in patients with ESRD with underlying chronic hypertension. Tachycardia and hypertension can be attenuated with supplemental short-acting agents or opioids titrated to effect. Following the stress of tracheal intubation, kidney transplant patients may develop hypotension before surgical incision, especially in patients who have been rendered hypovolemic from recent dialysis or in patients receiving renin-angiotensin blocking drugs.

Intraoperative monitoring may be limited to standard noninvasive monitors in younger, healthier transplant recipients and in select living donor recipients. Intraarterial blood pressure monitoring can be beneficial, especially in patients with uncontrolled hypertension, CAD, or heart failure. A radial arterial catheter, if used, is placed contralateral to a preexisting arteriovenous fistula and the femoral artery is typically avoided. Femoral access on the side selected for implantation is contraindicated due to the risk of hematoma or thrombosis adversely affecting the implanted graft. It is important to assess the risk versus benefit of arterial access in ESRD patients, as upper extremity arterial lines may jeopardize future arteriovenous access for dialysis. Pulmonary artery (PA) catheter or transesophageal echocardiographic monitoring may be considered in patients with advanced CAD, left or right ventricular dysfunction, and pulmonary hypertension but is rarely indicated otherwise. Central venous pressure monitoring may be employed in some centers; however, central venous pressure is not a reliable monitor of fluid status or responsiveness. The insertion of a central line provides reliable venous access for intravascular fluid resuscitation and transfusion, easy blood sampling, and access for administration of immunosuppression drugs and vasoactive infusions. In patients without a preexisting arteriovenous fistula or dialysis catheter, a central line allows urgent postoperative dialysis, if required. Many centers find central line insertion unnecessary; the risks and benefits of central line placement should be considered. Large-bore venous access is necessary for appropriate intravascular volume administration. Intravenous access can be challenging in some kidney transplant patients, as intravenous sites may be limited by the presence of an upper extremity arteriovenous fistula. Conversely, central venous access may be difficult to accomplish in patients with ESRD who have undergone multiple previous central venous dialysis catheter placements, especially if central venous thrombosis has been documented.

Maintenance of anesthesia is typically performed using a combination of intravenous and inhaled anesthetics. Volatile inhaled anesthetics are titrated to the level of surgical stimulation. Desflurane and isoflurane are not associated with nephrotoxicity. Although sevoflurane has potential nephrotoxic effects from the metabolites compound A and fluoride ion, detrimental effects on renal function have not been demonstrated in patients with renal insufficiency. Although large prospective studies are lacking in kidney transplant patients, the use of sevoflurane during kidney transplantation appears to be a reasonable anesthetic choice.

Analgesia during the intraoperative period can be provided with the synthetic opioids fentanyl, sufentanil, alfentanil, and remifentanil because their pharmacokinetics and pharmacodynamics are not affected by renal insufficiency. Morphine, oxycodone, and meperidine should be used sparingly in patients with renal failure because these drugs have active metabolites that accumulate in these patients.

Appropriate neuromuscular blockade during kidney transplantation may facilitate optimal surgical conditions; however, recovery from neuromuscular blockade may be variable in patients with ESRD regardless of the drug used. Vecuronium and rocuronium have prolonged durations of action in renal failure patients, because their clearances rely both on renal and hepatic metabolism. Cisatracurium is likely the muscle relaxant of choice in patients with ESRD, because it undergoes organ-independent clearance. Pancuronium is primarily eliminated by the kidneys, and probably should be avoided in patients with renal failure. For patients with ESRD who are undergoing kidney transplantation, judicious use of neuromuscular blocking drugs is a necessity. Titration to surgical conditions and close monitoring of the level of neuromuscular blockade are crucial.

The surgical procedure involves placement of the renal allograft in the left or right extraperitoneal fossa, although the right side is usually preferred ( Fig. 60.6 ). A vertical curvilinear incision 20 to 25 cm long is typically made, extending from the pubis symphysis to above the anterior superior iliac spine. The abdominal musculature is divided, and the peritoneum is entered and retracted. During the initial incision and dissection, surgical stimulation is increased and hemodynamic responses may be exaggerated in some patients. Adequate analgesia, depth of anesthesia, and muscle relaxation should be appropriately titrated to effect. The external iliac vein and artery are identified and mobilized. Occasionally, different vascular structures are chosen for the renal anastomoses. Heparin may be administered before clamping of the vessels. The external iliac vein is clamped first, and the renal vein anastomosis is performed. Next, the external iliac artery is clamped and the renal artery anastomosis is performed. During the anastomoses of the renal vessels, expansion of intravascular volume with balanced salt solutions should be initiated. Furosemide and mannitol are administered before reperfusion to stimulate diuresis. Mannitol, along with adequate intravascular volume resuscitation, decreases the likelihood of acute tubular necrosis in renal transplantation. Adequate intravascular volume expansion with crystalloid or colloids increases renal blood flow, which improves immediate graft function. At the time of removal of the vascular clamps, additional intravascular volume expansion may be required to stabilize hemodynamics. On rare occasions, removal of vascular clamps may be associated with acute bleeding requiring further resuscitation and transfusion. Hypotension following reperfusion will result in hypoperfusion of the graft. Hypotension may precipitate renal injury owing to ischemia and can contribute to vascular thrombosis of the graft. Appropriate decreases in the depth of volatile anesthetic and volume expansion will maintain adequate renal perfusion pressures in most patients. In the event of hypotension, adrenergic vasopressors are typically avoided because of renal vasoconstrictive effects. Hypotension unresponsive to volume expansion may require interventions to increase cardiac output, especially in high-risk patients. Invasive hemodynamic monitoring is invaluable in this situation. Inotropic agents may be necessary to maintain renal perfusion pressure; there is no consensus regarding which agent is preferred in kidney transplant patients. After completion of the vascular anastomoses, the donor graft ureter is implanted into the recipient bladder. The bladder is filled with antibiotic saline irrigation solution by way of a three-way Foley catheter, allowing for implantation of the donor ureter. A temporary ureteral stent may be placed as well. After completion of the bladder anastomosis, the wound is closed in layers. Neuromuscular blockade should be maintained until the fascial layer has been closed to prevent straining or coughing that could potentially disrupt the graft position or vascular connections. During emergence, exaggerated hemodynamic responses are common, especially in patients with poorly controlled hypertension. Appropriate titration of short-acting drugs to attenuate these responses upon emergence is helpful, especially in patients at risk for CAD. Careful neuromuscular blockade monitoring and appropriate administration of reversal agents are central to avoiding postoperative pulmonary complications. Sugammadex, a binding agent specific for rocuronium, forms an inactive complex that is primarily cleared by the kidneys. Clearance of this complex is reduced in ESRD patients, although removal of this complex using dialysis has been demonstrated. Sugammadex has been shown to be clinically effective in ESRD patients, however its safety has not yet been demonstrated in kidney transplant populations. ESRD patients may demonstrate delayed emergence from anesthesia and have exaggerated responses to opioids and sedative-hypnotics. Extubation of the trachea should occur after the patient demonstrates the ability to protect the airway, because kidney transplant patients are still considered a risk for aspiration of gastric contents at the completion of surgery.

Anesthesia for Kidney Transplant: Postoperative Management

After extubation of the trachea, the kidney transplant recipient requires careful monitoring in the postanesthesia care unit. Close monitoring of urine output in the initial postoperative period is important. Acute decreases in urine output should initiate a rapid evaluation of the etiology and appropriate treatment. A prerenal etiology should be treated with aggressive intravascular volume resuscitation. In some patients, additional invasive hemodynamic monitoring may be required. Postrenal etiologies owing to technical problems with the ureteral anastomosis may require early surgical re-exploration. Postoperative surgical complications include vascular thromboses, wound hematomas, and infection. Nonsurgical cardiovascular, pulmonary, and gastrointestinal postoperative complications are not unusual after kidney transplant; one institution reported a 90-day severe postoperative complication rate of 15%. High-risk patients with advanced cardiac and pulmonary disease may require further postoperative monitoring in the intensive care setting. In general, postoperative intensive care admissions for kidney transplant recipients are much less common than for liver and kidney-pancreas transplant recipients. One single-center study found a 6% rate of ICU admission following kidney transplant. The mortality rate in kidney transplant patients that required intensive care admission was higher than in nontransplant ICU patients.

Postoperative pain control is usually provided with synthetic opioid analgesics without active metabolites. Pain after kidney transplant is highly variable; in some patients, pain may be severe and challenging to treat effectively. Renal failure alters the pharmacology of most opioid medications; dose reductions are generally required in renal failure patients. In addition, chronic underlying pain conditions and opioid dependence may impact postoperative pain following kidney transplant; chronic pain conditions occur in 40% to 60% of dialysis patients. Patient-controlled opioid analgesia is commonly initiated in the postanesthesia care unit and continued for 24 to 48 hours. Regional anesthesia for kidney transplantation is controversial. One report demonstrated effective postoperative analgesia in kidney transplant recipients with epidural analgesia, however concerns for uremic coagulopathy and hypotension have limited its widespread use in kidney transplant patients. Although transversus abdominis plane block has been advocated for postoperative analgesia in kidney transplant patients, results from randomized controlled trials have been inconsistent.

Organ Matching and Allocation

Organ matching for kidney transplantation involves several steps to determine compatibility between donor and recipient. Initially, matching of the major ABO blood group is determined for all donors and recipients. Before the transplant surgery, a crossmatch is performed by mixing recipient blood with donor blood cells. This crossmatch is performed to identify any recipient antibodies that are reactive against donor antigens. Histocompatibility matching is an important part of the matching process, in which the human lymphocyte antigen (HLA) profile of the recipient is determined and compared with the HLA profile of the donor. Organ rejection by the recipient’s immune system is mediated by the recognition of mismatched (non-self) HLAs located on the surface of donor cells. Many standard HLAs are compared between potential donors and recipients before transplantation. In general, graft survival rates are worse with HLA-mismatched grafts. Although better immunosuppression has improved the overall survival rates for kidney transplants during the past 3 decades, the graft loss rate for HLA-mismatched kidneys has remained higher than HLA-matched grafts. For all potential recipients awaiting a deceased donor, their HLA profile is compared to the donor profile, and an appropriate donor-recipient pairing is made based on the best match. For living donors, HLA matching is performed well in advance of the surgery. The U.S. kidney allocation system implemented in 2014 prioritizes deceased donor transplantation for highly sensitized candidates, a group of candidates that have previously endured prolonged waitlist times before receiving organ offers. One-year analysis of the new kidney allocation system demonstrated a fourfold increase in the transplant rate for highly sensitized candidates with an overall 6-month graft survival rate that matched the years prior.

Anesthesia for Patients After Kidney Transplantation

After successful kidney transplantation, most patients are classified as having National Kidney Foundation stage 2 or 3 CKD with usual GFRs more than 30 mL/min. GFR typically deteriorates by 1.4 to 2.4 mL/min/year in renal transplant recipients. Posttransplant mortality increases as renal graft function deteriorates. Renal function is followed closely within the first few years after transplant to assess for rejection, which is identified by worsening organ function. In post–kidney transplant patients undergoing nontransplant surgery, renal function should be assessed before surgery. Most patients will be under the care of a nephrologist within the first years of a kidney transplant; assessment of the patient’s medical records or renal function tests should be obtained preoperatively. Rejection should be ruled out before nontransplant surgery, as surgery during an episode of rejection can increase morbidity.

Although successful kidney transplantation decreases overall cardiovascular risk in ESRD patients, cardiovascular disease is more prevalent in kidney transplant recipients compared to the general population and remains the most common cause of death in kidney transplant patients. As described previously, cardiovascular disease is involved in the pathogenesis of renal failure and is a consequence of kidney disease as well. Ischemic heart disease, cerebrovascular disease, and peripheral vascular disease significantly affect the survival of kidney transplant patients. Progression of preexisting CAD can occur in the posttransplant patient, as immunosuppression contributes to the development of de novo hyperlipidemia, hypertension, and diabetes. The incidences of hypertension (92%), hyperlipidemia (66%), diabetes (41%), and obesity (38%) are increased in kidney transplant recipients. Known CAD in kidney transplant recipients has been documented in 10 centers worldwide and 20% of selected populations, but the prevalence of CAD likely increases in the years following transplant. Because long-term studies on cardiac outcomes following nontransplant surgery in kidney transplant recipients are lacking, there are no specific recommendations for cardiovascular evaluations in kidney transplant recipients. For previous kidney transplant patients undergoing nontransplant surgery, the ACC/AHA guideline for perioperative cardiovascular evaluation for noncardiac surgery should be used to guide preoperative cardiovascular testing.

Other disease processes related to kidney disease and immunosuppression should be sought. Kidney transplant patients are at increased risk for posttransplant malignancies, anemia, and osteodystrophy. Infection is a constant concern in kidney transplant recipients, because they are at risk for both opportunistic and community-acquired infections. Cytomegalovirus (CMV) infection is the most common infection in kidney transplant patients, and it is rarely acquired by transfusion. CMV-negative blood should be used when transfusions are required in patients who are CMV negative.

Anesthesia for nontransplant surgery can be accomplished safely with general, regional, and local sedation techniques. Most anesthetic drugs are safe in posttransplant patients, assuming the presence of adequate hepatic and renal function. Although preoperative creatinine may be near normal in kidney transplant recipients, GFR in these patients is usually reduced, resulting in prolongation of the activity of drugs cleared by the kidneys. Obviously, drugs that cause nephrotoxicity should be avoided.

Indications for Pancreas and Kidney-Pancreas Transplantation

Pancreas transplantation provides patients with insulin-dependent diabetes mellitus a permanent source of endogenous insulin, thus restoring normoglycemia. SPK and PAK transplants are indicated in patients with diabetes and ESRD who are deemed appropriate candidates for kidney transplantation or who have already undergone kidney transplantation. PTA is indicated in patients with diabetes without indications for kidney transplantation and who have a history of severe frequent metabolic complications, including hypoglycemia unawareness, or who have a history of problems maintaining insulin therapy that result in intractable diabetic complications. Most patients who undergo pancreas transplant have type 1 diabetes mellitus. Rare indications for pancreas transplant include select cases of type 2 diabetes mellitus, chronic pancreatitis that has developed endocrine deficiency, cystic fibrosis with endocrine deficiency, and prior total pancreatectomy.

Previously pancreas transplant was reserved for younger patients, traditionally under age 40. For patients with diabetes and ESRD, older data found that SPK patients younger than 50 years had better reported survival rates than older patients. Recently, pancreas transplant has been considered for candidates over age 50, corresponding with population trends toward more aging diabetic patients. Recent single-center studies have demonstrated similar results in pancreas transplant recipients over age 50 compared to younger patients. These results suggest a future role for pancreas transplant expanded to older populations, a trend that has been observed in other solid organ transplant populations. Regardless of patient age, survival benefits in SPK are likely due to long-term decrease in CAD complications.

For patients with normal renal function who undergo PTA, long-term survival is the same as in patients receiving chronic insulin therapy. Pancreas transplant appears to have a favorable effect on the progression of retinopathy as well. The progression of retinopathy is decreased or reversed in a significant percentage of PTA patients compared to diabetic patients treated with conventional insulin therapy.

Pathophysiology of Pancreatic Insufficiency

Type 1 diabetes mellitus occurs secondary to destruction of pancreatic islet cells resulting in a permanent functional loss of the endogenous production of insulin, necessitating life-long exogenous insulin therapy. The underlying cause of type 1 diabetes mellitus remains unknown. Type 2 diabetes mellitus results from peripheral resistance to the effects of insulin. Both diseases produce chronic increases of blood glucose concentrations resulting in the multiorgan manifestations of diabetes.

The chronic complications of diabetes that have the greatest effect on patient morbidity and survival are those that affect the cardiovascular system. CAD, cerebrovascular disease, and peripheral vascular disease occur in patients with diabetes owing to acceleration of atherosclerosis. Both macrovascular and microvascular disease occurs. Patients with diabetes develop CAD earlier, are more likely to have atypical symptoms, and have a higher mortality rate from myocardial infarction than nondiabetics. Peripheral and autonomic neuropathies develop in diabetes, resulting in gastroparesis, lower extremity paresthesia, ulcerations, orthostatic hypotension, and labile heart rate and arterial blood pressure. Patients with diabetes have a high cumulative prevalence of blindness (16%), renal failure (22%), lower extremity amputation (12%), myocardial infarction (21%), and stroke (10%).

Acute complications of type 1 diabetes mellitus typically involve conditions associated with severe hyperglycemia, such as diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic coma. Hypoglycemia is a direct result of exogenous insulin administration. Patients with type 1 diabetes are prone to large fluctuations in blood glucose levels. Hypoglycemic episodes contribute to acute morbidity and mortality in diabetic patients. Hypoglycemia unawareness in particular can have a marked impact on quality of life and is a frequent indication for pancreas transplant.

Anesthesia for Pancreas Transplantation: Preoperative Evaluation

The preoperative evaluation for the patient undergoing pancreas transplantation involves an assessment of all of the potential acute and chronic complications of type 1 diabetes. Pancreas transplant centers pursue a comprehensive, multidisciplinary evaluation and selection process before listing candidates. The evaluation should address the organ systems most affected by long-standing diabetes, including the cardiovascular, renal, and neurologic systems. Assessment for the presence and severity of CAD should be undertaken in all candidates, including noninvasive ischemia testing, evaluation of ventricular function, and coronary angiography in select patients. Previously, patients considered for pancreas transplantation were younger than 50 years and had a lower risk for the cardiac and vascular sequelae of diabetes. Older patients are now considered for pancreas transplantation, but have a significantly higher risk for CAD and vascular disease. Strategies to reduce cardiac complications, such as maintenance of β-adrenergic blockade and continuation of drugs that decrease blood lipid concentrations during the perioperative period, should be applied when appropriate.

In most cases, pancreas transplantation involves a deceased-donor organ with a 24-hour maximum cold ischemia time; therefore, pancreas transplantation is considered an urgent procedure. Preoperative evaluation by the anesthesiologist should focus on any acute changes in the patient’s medical status, especially those involving acute diabetic complications such as ketoacidosis and hypoglycemia. Blood glucose measurements should be assessed closely before surgery and recent insulin administration should be noted. Most patients will have a preoperative variable-rate intravenous infusion of insulin with maintenance glucose during a period of fasting. Evaluation of renal function in all candidates is important before surgery. Most patients with diabetes listed for pancreas transplant have ESRD as well and will undergo SPK. A full evaluation of electrolytes, including creatinine and potassium, should be obtained before surgery. Serial trends in heart rates and arterial blood pressures in hospitalized patients should be assessed, as most patients will have a history of hypertension requiring multiple medications, especially patients with renal failure. Preoperative assessment of intravascular volume status is especially important in patients with ESRD on hemodialysis. Finally, a directed physical examination focusing on the airway and cardiopulmonary system should be performed. The incidence of difficult tracheal intubations in patients with long-standing diabetes was thought to be more frequent because of anatomic changes of the upper airway; however recent data does not demonstrate this. Nevertheless, attention to anatomic signs of a potentially difficult airway is important in patients with diabetes, especially those with cervical arthritis and significant obesity.

Anesthesia for Pancreas Transplantation: Intraoperative Management

General anesthesia with endotracheal intubation is performed for all types of pancreas transplantation except islet cell transplant, which is usually done under sedation in an interventional radiology setting. The surgical procedure is typically prolonged, and an adequate depth of anesthesia and muscle relaxation is required for optimal surgical conditions. Diabetic patients and those with ESRD have a high likelihood of gastropathy and may have an increased risk for aspiration of gastric contents. Administration of an oral nonparticulate antacid preoperatively should be considered. A rapid-sequence induction of anesthesia is the safest approach to securing the airway. Patients with diabetes, ESRD, cardiovascular disease, and autonomic neuropathy may be prone to wide fluctuations in heart rate and arterial blood pressure during induction and intubation. Vital signs should be closely monitored and maintenance of hemodynamic stability should be a primary anesthetic goal, especially during and immediately following anesthetic induction. Invasive monitoring is standard for pancreas transplantation. Arterial monitoring allows for beat-to-beat arterial blood pressure measurements, as well as access for analysis of arterial blood gases and blood glucose monitoring. Central venous access may be indicated for central administration of vasoactive infusions and immunosuppression drugs. Large-bore venous access is essential, and a temporary dialysis catheter may be useful for both resuscitation and postoperative dialysis if preexisting dialysis access is absent.

Central venous pressure monitoring is used in some centers; however, the usefulness of this practice has been questioned, as central venous pressure might not be a reliable indicator of intravascular fluid responsiveness. Arterial line placement before induction of anesthesia may be considered, especially in patients with severe hypertension or CAD. Anesthesia is typically maintained with a balanced technique using volatile anesthetics, opioids, and muscle relaxants. In patients with renal failure, medications should be chosen that are not dependent on the kidneys for elimination. All the caveats for the anesthetic management of patients undergoing kidney transplantation should be applied for patients undergoing SPK.

A midline surgical incision is made for both pancreas and kidney-pancreas transplant surgeries. Extensive retraction necessitates adequate muscle relaxation. Prolonged exposure of the abdominal viscera results in significant third-space losses; adequate volume expansion with crystalloid or colloids is often required. The pancreas graft is usually placed in the iliac fossa. The arterial vascular supply to the pancreas graft is usually provided by an anastomosis to the iliac artery. Usually the venous outflow from the pancreas is delivered to the iliac vein, which is associated with a lower rate of venous thrombosis. Alternatively, venous outflow may be directed to the native portal vein, which is the physiologically normal pattern of pancreatic venous efflux. There appears to be no significant advantage to portal venous drainage over systemic venous drainage for pancreas transplantation.

Pancreatic exocrine drainage can be delivered to either the bladder or the intestine ( Fig. 60.7 ). Although enteric pancreatic drainage is physiologically normal, this method is associated with surgical complications that can result in graft dysfunction, thrombosis, and early rejection. Exocrine drainage to the bladder allows for measurement of urinary amylase levels, which can be used to diagnose early rejection episodes before blood glucose levels are affected. Exocrine bladder drainage is associated with urologic complications and metabolic acidosis. Currently, most pancreas transplants utilize enteric drainage as there is no difference in graft or patient survival compared to bladder drainage.

Prior to completion of the vascular anastomoses during pancreas transplantation, blood glucose levels should be assessed at least hourly as levels frequently fluctuate in brittle diabetic patients. Blood glucose should be maintained at less than 200 mg/dL, using intravenous insulin and dextrose infusions if necessary. Sliding scale insulin infusion protocols may be applied. Dextrose prevents the development of ketoacidosis during the early stages of the procedure. However, some centers stop insulin infusion when the pancreas comes out of ice, re-starting after reperfusion only if hyperglycemia is observed. Before unclamping of the vascular anastomoses, adequate volume resuscitation should be initiated. Adequate cardiac preload and normal arterial blood pressures should be the hemodynamic goals before unclamping.

After unclamping of the vascular connections, heavy bleeding can occur. This is typically from retroperitoneal and mesocolonic collaterals that are missed during cold dissection on the back table. Maintenance of adequate graft perfusion pressure is critical. Hypotension should be corrected rapidly, and intravascular volume status should be optimized. If hypotension occurs because of myocardial dysfunction, intracardiac pressure monitoring or transesophageal echocardiography can assist in the diagnosis and may help to guide therapy. Blood transfusions, colloids, and vasoactive medications may be required for the treatment of hypotension after reperfusion of the pancreatic graft. Therapy should also be guided by frequent arterial blood gas analyses with assessment of electrolytes and hemoglobin.

One of the most important intraoperative care points for pancreas transplantation is the management of blood glucose following pancreas reperfusion. After unclamping, the pancreas may release insulin into the circulation within several minutes. Blood glucose should be measured approximately every 30 minutes for the remainder of the procedure. After successful transplantation, insulin requirements rapidly decline, and patients may be at risk for hypoglycemia. Delayed graft function can be identified by the presence of hyperglycemia. In this event, insulin infusion should be titrated to maintain blood glucose levels less than 200 mg/dL.

Anesthetic Management of Pancreas Transplantation: Postoperative Management

After the completion of surgery, full reversal of neuromuscular blockade, hemodynamic stability, normothermia, and the ability of the patient to protect the airway will facilitate tracheal extubation. Pancreas transplant patients should be monitored closely in the postanesthesia care unit and ICU. Regular blood glucose measurements should be continued in the postoperative period to avoid hypoglycemia. Electrolytes, complete blood count, and analysis of arterial blood gas should be obtained immediately postoperatively, because acid-base disturbances, anemia, and electrolyte imbalances are common. Euvolemia should be maintained. Depending on the patient’s age and underlying risk for CAD, serial troponins and ECG may be assessed for the presence of myocardial ischemia or infarction, because cardiac symptoms may be lacking in this population. Postoperative pain can be severe, given the extensive surgical wound and duration of surgery. Postoperative pain usually is managed with opioids in the perioperative period with transition to patient-controlled analgesia in the early postoperative period. Epidural analgesia may be appropriate for pancreas transplant recipients, although the risks of hypotension, dilutional coagulopathy, and spinal cord hypoperfusion in patients who may have severe microvascular disease have not been quantified. For SPK, the usual postoperative strategies for kidney transplant patients including close monitoring of urine output should be applied.

Surgical complications occur in 7% to 9% of all pancreas transplants and usually require reoperation. Technical complications are associated with the potential for graft loss and patient morbidity. Unlike kidney transplantation, technical complications are the most common cause of pancreas transplant graft failure in the first year after surgery. Graft thrombosis is the most important early complication and requires emergent surgical exploration. Intraabdominal bleeding can occur secondary to coagulopathy induced by anticoagulation for the treatment of graft thrombosis. Late complications include bladder or enteric leaks, intraabdominal sepsis, and rejection. Rejection is the most common cause of long-term graft loss after 1 year and occurs in 15% to 21% of pancreas transplant recipients within 1 year of surgery.

Organ Matching and Allocation

The organ matching process for pancreas transplantation is similar to that for kidney transplant organ matching. Blood group and HLA matching are initially performed to match the donor and recipient, followed by a crossmatch at the time of surgery. Most organs allocated for pancreas transplantation are for diabetic recipients younger than 40 years. However, over the past decade, the average transplant recipient’s age has increased because of the allocation of more organs for patients with type 2 diabetes. In 2016, the number of pancreas transplants performed in patients over age 50 increased to 240 from 185 the year prior, corresponding with an increase in type 2 diabetics undergoing pancreas transplants.

Anesthesia for Patients After Pancreas Transplantation

After successful pancreas transplantation, long-term normoglycemia is expected. For patients with a history of previous pancreas transplant presenting for surgery, a comprehensive posttransplant history of any episodes of surgical complications and episodes of rejection should be obtained. Blood glucose concentrations should be measured on the day of surgery. A detailed history and review of medical records focusing on CAD, renal disease, and vascular disease is critical. Although the end-organ progression of diabetes is favorably impacted by pancreas transplant, pancreas transplant patients have a high prevalence of these conditions compared to the general population. Disease progression can occur despite successful pancreas transplantation. Therefore, the preoperative cardiac evaluation for the post-pancreas transplant patient undergoing surgery should be guided by ACC/AHA Guideline.