Medical and surgical advances have made solid organ transplantation widely available, and many centers perform kidney and liver transplantation on a regular basis. Bowel, heart, and lung transplantations are more centralized and performed at only a few centers. As organ transplantation becomes more frequent, anesthesiologists will see a larger number of patients presenting for transplantation or those who have had transplantation and are undergoing other surgeries. A thorough understanding of preoperative considerations, intraoperative management, and posttransplant physiologic changes is critical to assure a good outcome for these fragile and complex patients.

In general, successful transplantation is more common in children than adults, and both rejection and infection are less common in infancy than in childhood (1,2). One must account for the metabolism and the route of excretion of drugs in these patients. For example, although morphine is metabolized in the liver (CYP450), the metabolite is excreted by the kidney. Side effects of immunosuppressive drugs can be significant. Cyclosporine can produce renal vasospasm resulting in hypertension. Tacrolimus (but usually not sirolimus) may cause hypertrophic cardiomyopathy in children. Because these patients may require anesthetics for posttransplant procedures such as biopsies, endoscopies, and other surgeries, an understanding of the anesthetic implications of the patient who has undergone a transplantation as well as their intraoperative care is necessary (3).

RENAL TRANSPLANTATION

Indications for kidney transplantation are end-stage renal disease (ESRD) and chronic renal failure. Glomerulonephritis, congenital disorders (aplasia, hypoplasia, or dysplasia), obstructive uropathy, focal segmental glomerulosclerosis, and reflux uropathy are the most common causes of the disease in children (4). Five-year posttransplant survival rates are excellent and posttransplant survival has improved greatly even for infants in recent years (5).

PREOPERATIVE ASSESSMENT

In pediatric renal transplantation, the goal is to minimize the time the child needs to spend on dialysis (6). If possible, preemptive transplantation is desirable. Early transplantation will decrease the incidence of progressive growth failure, renal osteodystrophy, and developmental delay, the hallmarks of ESRD in children. Living-related donor transplantation is widely performed and preferred over cadaveric grafts (7). The latter shows somewhat inferior long-term graft function and survival.

  1.   Children will go through a thorough pretransplant evaluation before getting on the transplant list. The evaluation will include the etiology and course of the disease and associated disease processes.

  2.   The patient’s medication list should be carefully reviewed. Great attention should be paid to recent laboratory data that can reveal electrolyte and hematologic derangements.

  3.   The time of the last dialysis session needs to be considered. If the patient recently underwent dialysis, hypovolemia may be present. If the patient did not receive dialysis recently, hypervolemia and the potential for hyperkalemia need to be addressed.

  4.   Anemia is likely to be present, although most of these patients receive recombinant erythropoietin.

  5.   Platelet dysfunction is expected, although the platelet count may be normal. Infants and small children should be evaluated for a hypercoagulable state, as the risk of vascular thrombosis of the graft is increased in this population.

  6.   Meticulous documentation of preexisting neurologic dysfunction is important as ESRD can cause a variety of peripheral neuropathies and central nervous system dysfunctions.

INTRAOPERATIVE MANAGEMENT

  1.   Premedication with sedatives before renal transplantation is at the discretion of the anesthesiologist, but is likely to be helpful. These children have had many medical encounters and are likely to be anxious.

  2.   The surgical team dictates preoperative antibiotics, but they are recommended, as these patients are already immunocompromised by their disease process.

  3.   General endotracheal anesthesia is standard for kidney transplantation. Inhalational induction of anesthesia is acceptable in most elective cases, but intravenous (IV) induction is preferred in patients who have existing IV access or have a full stomach. Balanced anesthesia with a volatile anesthetic, opioids, and muscle relaxants is usually used. Sometimes, general anesthesia is combined with epidural anesthesia, which can also be used for postoperative pain control. Early concerns of increased hemodynamic instability with the addition of epidural anesthesia have proved to be unwarranted. Good intraoperative and postoperative analgesia with epidural catheters provides increased hemodynamic stability (8).

  4.   In selecting medications and doses, the volume of distribution must be considered as it is likely to be higher in hypervolemic patients or lower in the recently dialyzed hypovolemic patient. Decreased renal excretion of medications must also be considered; although one can expect the rapid normalization of renal function after surgery in a successful graft. The possibility of graft failure must also be kept in mind.

  5.   The use of succinylcholine for rapid-sequence induction is controversial, as it can raise serum potassium to dangerous levels and cause conduction abnormalities in patients with preexisting elevated serum potassium. Rocuronium, although hepatically metabolized, has a slower onset of action in children with ESRD, but duration of action is not prolonged (9).

  6.   In most cases, standard intraoperative monitoring and measurements of central venous pressure (CVP) provide sufficient information for the anesthesiologist. The blood pressure cuff must not be placed on the same arm as an existing arterio-venous fistula. In selected cases (e.g., very small child, significant coagulopathy, poorly controlled hypertension), an arterial line can be justified, but arterial punctures are often avoided to preserve the vessel as a potential arteriovenous (AV) fistula site.

  7.   Fluid management is guided by the patient’s volume status and CVP. To assure good organ perfusion, a CVP higher than 12 mm Hg is recommended. Balanced salt solutions such as Lactated Ringer solution, although they contain small amounts of potassium, can be used, but washed, irradiated red blood cells should be utilized to minimize the risk of hyperkalemia (10). It is particularly critical to ensure adequate filling pressures when the circulation to the transplanted kidney is established (see subsequent text).

  8.   Mannitol (0.25 to 0.5 g/kg), often in combination with furosemide (0.5 to 1 mg/kg), is usually administered before the graft is placed in circulatory continuity, both for its diuretic and its free-radical scavenging effects.

  9.   The surgical technique in pediatric renal transplantation is very much dependent on the patient’s age and size.

         a.   In the younger child, it is more likely that the graft will be placed intraperitoneally through a large midline incision. The vessels of a graft from an adult donor will be anastomosed to the aorta and inferior vena cava (IVC) to avoid size discordance.

         b.   In older children and adolescents, extraperitoneal pelvic placement of the graft is customary. In larger children and adolescents, the size of the iliac vessels makes them acceptable anastomosis sites.

10.   The hemodynamic consequence of performing such anastomoses needs to be considered. It must also be kept in mind that upon release of the renal artery clamp, a large portion of the circulating volume is diverted to the graft, resulting in systemic hypotension if filling pressures are inadequate. One should anticipate such an event and assure an adequate (moderate to high) CVP before release of the clamp and also be prepared to treat hypotension if it should occur.

11.   Acidosis due to reperfusion of the graft can further contribute to the hypotension.

12.   Blood transfusion is more frequent in the pediatric patient population presenting for renal transplantation as compared to their adult counterparts. This is again due to the relationship between graft size and recipient total blood volume.

13.   The anesthesiologist will be asked to administer immunosuppressant medications intraoperatively. The transplant team should guide the doses and timing of these drugs. Usually a large dose of glucocorticoid in combination with an immunomodulating drug will be given.

14.   Most patients can be extubated in the operating room. Criteria for extubation are similar to any other abdominal surgery. Postoperatively observation in a pediatric intensive care unit (PICU) or specialized transplant unit is recommended. Postoperative pain can be managed with either epidural analgesia or patient-controlled analgesia (PCA) (8).

15.   Children who are kidney transplant recipients may have a slight elevation in their creatinine levels even with excellent graft function. In the absence of other findings, this is not necessarily a sign of impending graft failure or rejection (3). Chronic, not acute, rejection is the most common cause of graft failure.

LIVER TRANSPLANTATION

The first successful liver transplantation was performed in 1967. Major surgical advances include living donor transplantation, split- or reduced-size liver transplantation, and cadaveric grafts. Amongst the major medical advances are improved preoperative and postoperative care, new immunosuppressive regimens, and improved protocols for preempting and managing posttransplant complications. One-year survival is >90% (11,12). Risk is increased in infants under 9 kg, largely due to vascular complications (13).

Primary liver disease is the most common indication for liver transplantation in the pediatric population, extrahepatic biliary atresia being the single most frequent diagnosis (14). Other indications include certain inherited metabolic disorders (α₁-antitrypsin deficiency, ornithine transcarbamylase deficiency), Alagille syndrome, autosomal recessive polycystic kidney disease, fulminant hepatic failure, primary malignancies such as hepatoma or hepatoblastoma, or biliary duct tumors (15). Regardless of the etiology of the end-stage liver disease, the pathophysiology of liver failure is the same.

PREOPERATIVE ASSESSMENT

Pediatric liver transplant recipients have multiple organ systems affected by their disease. The preoperative assessment should start with the etiology of the liver disease and the range of associated abnormalities.

  1.   The general medical and nutritional condition of the patient should be assessed.

  2.   Patients typically exhibit high cardiac output and low systemic vascular resistance due to circulating vasoactive substances and arteriovenous (AV) shunting. There is an increase in the mixed venous oxygen saturation and a decrease in the AV oxygen difference. They exhibit decreased sensitivity to catecholamines and vasopressors (16,17).

  3.   Ventilatory impairment may occur due to intrapulmonary shunting, impaired hypoxic pulmonary vasoconstriction, and reduced functional residual capacity (FRC) secondary to organomegaly and the presence of ascites. Pulmonary hypertension may also be present.

  4.   Prerenal azotemia from diuretic use or even hepatorenal syndrome may be present. Preoperative sodium and potassium derangements can be difficult to manage, necessitating preoperative or even intraoperative continuous hemofiltration.

  5.   Encephalopathy, cerebral edema, and increased intracranial pressure (ICP) can develop. Intractable cerebral edema, intracranial hypertension, and severe encephalopathy may at some point become irreversible and may be a contraindication to transplantation; multidisciplinary consultation must be convened in such cases.

  6.   Gastric emptying is delayed.

  7.   Portal hypertension will lead to ascites formation and the development of esophageal and gastric varices, which may bleed.

  8.   Hypersplenism will result in thrombocytopenia.

  9.   As there is impairment in the metabolic function of the liver, drug clearance is altered. Coagulation and glucose homeostasis disturbances reflect decreased liver synthetic activity.

10.   Great attention should be paid to hematologic parameters as anemia and thrombocytopenia.

11.   Serum electrolytes and ammonia level should be evaluated. Hyponatremia is common and difficult to correct.

12.   Albumin levels are generally low, reflecting malnutrition and diminished hepatic synthetic capacity.

INTRAOPERATIVE MANAGEMENT

  1.   Preoperative sedation should be used only with great caution. Patients waiting for liver transplantation can have varying degree of encephalopathy and increased ICP. Furthermore, derangement in metabolism makes them more susceptible to the sedative effects of benzodiazepines.

  2.   Because these patients have increased intra-abdominal pressure from ascites and organomegaly as well as delayed gastric emptying, they warrant rapid-sequence induction and intubation. The risk and benefit of rapid-sequence induction should be weighed against the possibility of presence of increased ICP, and precautions should be taken to ensure that the cerebral hemodynamic responses to laryngoscopy and intubation are adequately blunted.

         a.   A cuffed endotracheal tube is recommended in all age groups as pulmonary compliance changes during the different phases of surgery. Ventilation modes that deliver consistent tidal volumes with decelerating flow patterns (pressure-regulated volume control or volume guaranteed pressure-controlled ventilation) are useful.

         b.   Adequate preoxygenation is required; the reduced FRC from ascites and organomegaly may result in rapid desaturation.

         c.   The presence of pulmonary hypertension compounds the difficulty with ventilation–perfusion mismatch and the efficiency of oxygenation.

         d.   Therapeutic paracentesis before induction is a consideration if the amount of ascites is large.

  3.   Large-bore IV access in the upper extremities is mandatory, along with the ability to monitor CVP and intra-arterial blood pressure. If adequate large-bore upper extremity lines cannot be placed, a second large-bore central venous catheter can be substituted. Devices for the rapid infusion of warmed fluids should be ready in the operating room.

  4.   Maintenance of anesthesia can be achieved in various ways. More important than the actual anesthetic technique chosen is hemodynamic and homeostatic stability during all phases of the surgery (16–18).

  5.   Hypothermia should be avoided as it predisposes the patient to dysrhythmias, coagulopathy, and impaired renal function.

  6.   As coagulopathy is common in liver disease and massive transfusion should be anticipated during surgery, laboratory support must be readily available. Some centers advocate the use of the thromboelastogram, which provides real-time information on clotting, thrombolysis, and clot stability.

  7.   The procedure of liver transplantation is commonly divided into three phases: preanhepatic or dissection, anhepatic, and postanhepatic stages. All three phases have different anesthetic considerations.

         a.   The preanhepatic phase begins with surgical incision and ends with removal of the liver from the circulation.

                  i.   In this stage, the biggest concern is the blood loss secondary to coagulopathy. The dissection may be even more difficult in patients with biliary atresia who have had Kasai procedures because of adhesions and scarring from prior surgery.

                 ii.   Correction of coagulopathy, maintenance of circulating blood volume with appropriate hematocrit, close monitoring of glucose homeostasis, and temperature maintenance are the main anesthetic issues in this phase.

                iii.   Maintaining good preload is beneficial before the anhepatic phase, as cross-clamping the vena cava will result in an acute decrease in preload and cardiac output. Children, however, seem to tolerate this relatively well.

                iv.   When large volumes of blood products are rapidly transfused, especially fresh frozen plasma, meticulous attention must be paid to ionized calcium levels, which may fall precipitously as calcium is bound by citrate.

                 v.   Venovenous bypass can be established in this phase if a significant decrease in mean arterial pressure and cardiac output is noted after a trial of cross-clamping of the IVC (19). The technique has the advantage of decreasing splanchnic venous congestion and bowel edema, decreasing lower extremity edema, and counteracting the decrease in venous return and cardiac output. Risks of venovenous bypass are hypothermia, air- or thromboembolism, and trauma to the cannulated vessels and nerves that surrounds those vessels. This is performed only rarely in children as compared with adults.

         b.   The anhepatic phase begins with removal of the native liver from the circulation by cross-clamping the vessels and ends with reperfusion of the graft liver through venous circulation.

                  i.   The goals during this stage are hemodynamic stability and correction of metabolic abnormalities.

                 ii.   It is important to maintain cardiac output and vasopressors are often needed. Fluid administration should be guided by CVP monitoring, as care must be taken to avoid overload and congestion of the new liver after reperfusion. For this reason, and in contradistinction to kidney transplantation, a low CVP (usually 4 to 8 mm Hg) should be sought. Congestion of the newly transplanted liver can lead to rapid failure of the graft and must be assiduously avoided. Dynamic indices of volume responsiveness such as systolic pressure variability have been shown in some, but not all, studies to be useful guides to infusion (20,21).

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