<\/p>\n
<\/p>\n
<\/p>\n
Infectious Diseases <\/strong><\/p>\n 80% occurrence in first post-operative year (3). If possible, these patients should be isolated in the ED for their protection. Similar infections are common to transplants across the board due to immunosuppression. Many transplants require lifelong full dose immunosuppression. Often in the subacute setting the immunosuppressant \u0093cocktail\u0094 or dosage is altered to minimize complications and toxicity. Impaired humoral immunity leads to bacterial infection. Decreased cell mediated immunity leads to opportunistic infections (TB\/Fungal\/Protozoan) and viral infection. The most important viral infection is Cytomegalovirus (CMV). It can be most problematic if the patient is CMV na\u00efve and receives a CMV positive allograft. The CMV from the graft will attack the immunosuppressed host. Recipients and donors are screened routinely for CMV and hepatitis to avoid this complication. Even if the patient has had CMV and has sensitized T-Cell mediated immunity with immunosuppression, they may have a reactivation of disease. The pulmonary system is the most commonly affected in the post-transplant population (as in normal patients). Fever or pulmonary symptoms should initiate a search for tissue invasive infection so that early diagnosis and specific therapy may begin. Central nervous system infection is much more frequently seen in the transplant recipient than the non-immunocompromised population. A low threshold should be established for neurologic workup in the patient with a change in mental status or unexplained fever. As it does in any immunocompromised host, this may necessitate a head CT scan and lumbar puncture. There are patterns of infection which may be anticipated, in relation to the time interval following the transplant (3,4). If the EP understands these patterns, then a logical empiric therapy may be initiated while definitive diagnosis is pending. Infection is almost always a possibility with any presentation in the immunocompromised transplant patient.First Month – Post-Transplantation<\/em> – Mostly Bacterial Pathogens will be causative.<\/p>\n Typically Staph\/Strep.; also look to the transplanted organ as a potential source of latent infection. May Reactivate Latent Viral Disease (Hepatitis B\/C, CMV, EBV). Empiric Treatment<\/strong> – 3rd Generation (anti-pseudomonal) Cephalosporin, plus Ampicillin\/Sulbactam.<\/p>\n Beyond First Month Post-Transplant<\/em> – Typical pathogens are again Staph\/Strep and additionally Nocardia\/Listeria\/Tuberculosis.<\/p>\n Atypical Infections include viruses of the Herpes Class – which often disseminate and may even prove fatal; Simplex I or II commonly. CMV – Has a peak incidence at 6 weeks and occurs in 30-75% of recipients (particularly if recipient negative\/donor positive). EBV – May lead to Lymphoproliferative Disorder\/Lymphoma which is treated by decreasing the immunosuppression.\u00a0 Hepatitis B\/C: if recipient was positive the reinfection rate of the allograft is 86%. Empiric Treatment<\/strong> – Ganciclovir\/Foscarnet Fungal Infection – Candida, Aspergillus, Cryptococcus. Do not forget to order fungal cultures (especially of urine in renal transplant recipients). Empiric Treatment – <\/strong>Fluconazole or Amphotericin B Protozoa Infections – PCP\/Toxoplasmosis\/Giardia.\u00a0 Incidence much decreased with the use of TMP\/SMX prophylaxis. Usually diagnosed via bronchoalveolar lavage (not in ED). CXR, Sputum cultures. Hypoxia often evident (administer Steroids). Empiric Treatment <\/strong>– TMP\/SMX 5mg\/Kg QID.<\/p>\n The usual approach is to initiate therapy for bacterial pathogens unless a high clinical suspicion of another source presents itself from the history or physical examination. The difficulty again is that these therapies are empiric and often the EP will not be able to isolate the etiology of the disease process affecting any individual patient. This can prove frustrating to the clinician, but recall that no one else can do better.<\/p>\n Primary Graft Failure<\/strong>: A complication usually acute and seen at the transplant center. This usually presents as an acute decompensation of the function of the graft. Failure may be due to harvest technique, ischemic time, or reperfusion injury. Failure often is precipitated by inadequate organ perfusion or inadequate exocrine drainage (pancreas\/liver). May also be confused with acute rejection (heart\/kidney). Vascular Complications:<\/strong> Present clinically as organ failure or as colic-type pain. Transplanted organs do not have the same somatic innervation that native organs do. Pediatric transplants have a higher incidence of vascular compromise due to the decreased luminal diameter of their arteries (same underlying reason as respiratory diseases in pediatrics). Problems may occur at venous or arterial anastomosis. Gold standard in diagnosis is angiogram but non-invasive studies are also available. Duplex ultrasound or spiral CT are excellent diagnostic tools in the right hands. Diagnostic modalities available may be specific to your center. Rejection: <\/strong>\u00a0Again, the clinical presentation is not straightforward. The patient\u0092s end-organ function will be compromised or nonspecific pain may be the complaint. The presentation may also resemble infection or immunosuppressant toxicity. Rejection is an immune mediated attack of host on donor organ. Unfortunately 60% – 80% of recipients experience one or more episodes in the first post-operative year. Rejection is divided into Hyperacute, Acute, and Chronic depending on the time course. The diagnosis is established by organ biopsy. This process is difficult to differentiate from drug toxicity. In the ED organ function is evaluated as a marker. Empiric Treatment<\/strong> Methylprednisolone 500 to 1000mg. IV. Evaluate End Organ Function<\/strong> – Workup varies with the transplanted organ. The physician must remain cognizant that function may be impaired by many factors. Kidney<\/strong> – The most commonly transplanted organ. Death is rare because failures may be maintained on dialysis. Full tissue type HLA-matched do better. Long term survival is better in living related vs. cadaver donor organs. If creatinine is elevated consider rejection vs. drug toxicity.<\/p>\n If the patient has hypertension<\/em> think anastomosis, immunosuppression or native kidney problems. If febrile<\/em> think gram negative and fungal infections (do not forget urine fungal cultures). Imaging: <\/strong>Consider CT or Renal Flow Scan if creatinine is elevated, proteinuria more than trace or evidence of infection. Consider Renal Biopsy in conjunction with the transplant team.<\/p>\n Liver <\/strong>– Second most common transplant. Five-year survival is near 80%. No tissue matching is needed The critical factors are ABO Type and size of the graft. Also, in living related donors the adequacy of the vascular pedicle is important.<\/p>\n Imaging<\/strong>: US or CT to evaluate any abdominal complaint – studies show that physical exam is unreliable and that most patients with significant pathology such as graft failure, abscess, obstruction, and appendicitis had documented soft and nontender physical exams (2). Definitive diagnosis may require biopsy. Other: <\/strong>Do not forget drains or tubes as a source of infection or pain; some patients carry exogenous equipment into the post-op period.<\/p>\n Heart:<\/strong> Lifelong high-dose immunosuppression is needed. Five-year survival is 70%. ABO Type and size no full HLA Typing required. Remember Denervated Hearts do not have Angina.<\/em> CHF or arrhythmia should be admitted.<\/p>\n EKG: <\/strong>Many patients carry their own comparison cardiogram. Imaging: <\/strong>CXR. Strongly consider echocardiogram for any pulmonary\/chest complaints. Echocardiogram can help elucidate serious diagnoses such as pericarditis, infarction\/ischemia, or tamponade. Regional wall motion abnormalities can assist in localizing pathology.<\/p>\n Lung:<\/strong> Three-year survival is 56%. No HLA match is required. ABO and size considerations are important. May do single, double or heart & lung procedures. Poor natural protection exists in the transplanted organ. Ciliary function and macrophages are impaired. Cough is decreased post surgery. Any pulmonary complaint may be rejection. Donor lungs are seeded with many infections: nosocomials, gram negative, and opportunists (often from an ICU\/Ventilator). Poor blood supply (bronchial arteries are not re-attached) so transplanted lungs are relatively avascular and may have problems with anastomosis: necrosis, infection or dehiscence. Advanced imaging studies should be considered if no apparent abnormality presents itself with the basic workup and plain radiograph. Pulmonary complaints or hypoxia must be assumed to have a pulmonary etiology until another diagnosis can be identified.<\/p>\n Pulse Ox: <\/strong>Hypoxia = Admission Imaging: <\/strong>CXR \/ CT Thorax<\/p>\n Pancreas:<\/strong> Three year graft survival is approximately 51%, patient\u0092s survival is approximately 88%. Usually present with hyperglycemia or peritonitis. If organ is failing metabolic derangement may be seen first (glycemic control) CT is probably the study of choice for further evaluation. If peritonitis, consider pseudocyst, abscess, or necrosis. Ultrasound is usually a good first test for these patients.<\/p>\n Imaging: <\/strong>US or CT<\/p>\n Intestine: <\/strong>Three year survival about 45%. Included for completeness, but very few are done annually. As a graft there are many technical limitations. Poor vascular supply, high rate of rejection and poor function. Endoscopy and biopsy are probably most sensitive and specific but only in very skilled hands. Most centers do not routinely endoscope the small bowel. Therefore the imaging study of choice is contrast enhanced CT scan.<\/p>\n Imaging<\/strong>: CT or Endoscopy<\/p>\n Bone Marrow:<\/strong> HLA Typing is critical. ABO Type is not as important. Less are performed since studies have demonstrated no benefit for breast cancer rescue therapy, which had been one of the most common indications. Transplants are used for aplastic anemia, thalassemia major, ovarian cancer and chemotherapy induced marrow failure. Preparation includes complete destruction of native marrow. If any native WBCs remain, then the graft will be rejected. Typically these patients do not require lifelong immunosuppression. If the graft takes, they are cured. Another unique complication to this group is Graft vs. Host Disease (GVHD). The donated marrow recognizes the host as foreign and begins an immune attack on the host. This requires emergent immunosuppression and has a 33% mortality.<\/p>\n <\/p>\n Drug Toxicity (Immunosuppressant Therapy)<\/strong> – Most transplant patients are on some \u0093cocktail\u0094 of immunosuppressants. These mixtures usually combine complimentary agents to suppress cell mediated and humoral immunity and are selected to minimize their combined toxic complications. Most are hepatically metabolized and renally excreted. Emergency Physicians should be wary in prescribing for these patients to avoid drug interactions and toxicity. General Precaution: <\/em><\/strong>avoid all NSAIDs (renal compromise) and oral contraceptives (thrombotic events). Also no live virus vaccinations (dT and rabies are acceptable).<\/p>\n Following is a brief discussion of some of the most common elements used in immunosuppression therapy with their side effects and notable toxicity.<\/p>\n Significant Drug Reactions which affect levels of Cyclosporine and Tacrolimus<\/em><\/strong><\/p>\n Decreased Levels of Immunosuppressant<\/strong><\/p>\n Increased Levels<\/strong><\/p>\n Clarithromycin Ethanol Verapamil Diltiazem Fluconazole Itraconazole Ketoconazole Erythromycin Cimetidine<\/p>\n Phenytoin Barbiturates Nafcillin Rifampin<\/p>\n Azathioprine (Imuran):<\/strong> Inhibits both B & T Cell mediated immunity and the antigen recognition process of the immune system. There is direct dose-related bone marrow toxicity, reversible hepatotoxicity and lymphoma. Mucocutaneous problems are often the presenting complaint. Patients have oral bullae and swelling.<\/p>\n Figure 2: Azathioprine induced stomatitis and gingival swellingCyclosporine (Sandimmune, Neoral)<\/strong>: Directly inhibits T-Cell Proliferation (decreases CD4) without marrow suppression. Unfortunately dose dependent renal and hepatic toxicity are common. It is also associated with insulin resistance and oncologic disease. Trough drug concentrations are followed (random levels are not useful; don\u0092t order them). Tacrolimus (FK506, Prograf):<\/strong> Very similar to cyclosporine in function and toxicity and is used in its place. Drug levels are also available. Similar to cyclosporine hepatic nephrotoxicity and lymphoma. Also hypertension, diabetes, hyperkalemia and hypercholesterolemia are seen. \u00a0new sirolimus has no nephrotoxicity Muromonab-CD3 (OKT3, Orthoclone):<\/strong> Purified monoclonal antibodies against human T-Cells. Used mostly for acute rejection resistant to therapy with steroids. Presenting complaints are flu like symptoms. Also may produce an aseptic meningitis. Levels of drug are followed indirectly by monitoring trough CD3 lymphocyte levels. Mycophenolate mofetil (Cellcept): <\/strong>Antithymocyte globulin with anti T & B Cell activity. Usually used as a rescue therapy in cases of acute rejection. Similar symptoms to OKT3. Steroids:<\/strong> Inhibit release of inflammatory mediators and disable macrophage, T & B Cell mediated immunity. We are familiar with many of the side effects of long term use: Cushing\u0092s Syndrome, bone demineralization, impaired healing, cataract formation, and GI irritation.<\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n Resuscitation:<\/strong> Besides the complications that have already been covered what special considerations must the EP have for this patient population? Our colleagues in medicine and surgery expect this to be our area of expertise. Cardiac Transplant:<\/strong> 1)\u00a0 Bradycardia- No vagal attachment so Atropine is not effective<\/em> for symptomatic bradycardia. Go immediately to pacing. 2)\u00a0 Hypotension – Myocardium is sensitive to circulating catecholamines. Both contractility and rate will respond. The preferred drug has been Isoproterenol (Isuprel) simply because surgeons and cardiologists have had the most experience with this medication – 1-4mcg\/min (to max 10mcg). EP’s are expert in resuscitation and realize that there are other catecholamine-based inotropes.\u00a0 As usual start with crystalloid IV fluids. Try to avoid transfusion as many antibodies are often present in these patients. 3)\u00a0 Cardiopulmonary Symptoms – In the transplanted heart accelerated coronary artery disease is well described. It is thought to be a form of late rejection causing a diffuse fibrointimal hyperplasia. Ischemia will present with nonspecific symptoms such as CHF, fatigue, or GI symptomatology. Identifying infarction is difficult. Usually there is no angina. The EKG may be difficult to interpret. Commonly two P-Waves may be seen; both donor (linked to QRS) and native (recipient\u0092s). A new atrial arrhythmia, unexplained tachycardia, or greater than 20% decrease in total voltage should raise suspicions of possible effusion or ischemia. Ask! The patients often carry copies of their electrocardiograms. Echocardiogram may be helpful demonstrating wall motion abnormalities and impaired relaxation or new valvular regurgitation. Long-term Complications:<\/strong> 1)\u00a0 Malignancy – Relative risk is about four times the general population. Thought to be due to long-term immunosuppression disabling the host cancer fighting capacity. 2)\u00a0 Hyperlipidemia 3)\u00a0 Diabetes 4)\u00a0 Accelerated atherosclerosis Summary<\/strong> Always err on the side of the patient. As signs and symptoms of disease and organ failure are attenuated by immunosuppressive therapy, approach diagnosis and disposition with caution. Logical initiation of empiric therapies particularly for bacterial pathogens, while obtaining diagnostic studies may decrease morbidity. Utilize the resources available to you. These patients have specialists from the transplant center who are very helpful. Consultation should routinely be obtained prior to disposition. Rapid and accurate diagnosis of post transplantation infections and organ rejection will preserve graft function and decrease patient morbidity. The EP may also help the patient and their family by educating themselves and directing them to good information resources. Two web sites that address common questions and myths are, www.transweb.org\/myths\/myths.htm<\/a> and www.organdonor.gov\/myth.html.<\/p>\n Before prescribing any medication in a transplant patient be certain to consider the potential for interaction with the graft and the other medications the patient is using. Not every presentation has to do with the graft or attendant medications, but we should assume that it does.<\/p>\n <\/p>\n <\/p>\n Do not Give FFP<\/p>\n LIVER TRANSPLANTATION Although generally supportive, medical treatment for chronic end-stage liver disease does little to prolong life or improve its quality. This is especially true after serious complications, such as coma, GI bleeding, or uremia, develop. Salvage after acute hepatic failure through medical treatment is equally discouraging, with rates ranging from 5 to 20 percent. [111] By contrast, in the cyclosporine era, the overall 1-year survival for orthotopic liver recipients is greater than 75 percent (see Table 55-1) (Table Not Available) . [66] Longer-term survival is also relatively high, [112] and the quality of life is considered markedly improved for a high proportion of transplant survivors. [112] [113] As a consequence, some 2,500 liver transplants are performed in the United States annually, representing perhaps one-half the number needed. [112] Almost all these procedures are orthotopic, in which the allograft is implanted in anatomic position following native hepatectomy. Ra rely, heterotopic (sometimes called auxiliary) transplantation, in which the native liver is left in place, has been used to treat reversible hepatic failure in patients too unstable for the orthotopic operation. [114] Pathophysiology and Management of End-Stage Liver Disease Considering the numerous synthetic and metabolic functions of the liver (Ch. 17) , the manifestations of end-stage liver disease extend to virtually every other organ system. The central nervous system may be affected by encephalopathy ranging from mild confusion to deep coma. This may be exacerbated by electrolyte abnormalities, such as hyponatremia, and worsened by GI bleeding. In fulminant hepatic failure, encephalopathy must be distinguished from cerebral edema, which may require CT scanning. Circulation is usually hyperdynamic with reduced systemic vascular resistance and increased cardiac output, and low-normal blood pressure, despite reduced plasma volume. ——————————————————————————– 1985 Pulmonary gas exchange may be adversely affected by atelectasis from abdominal distention and pleural effusion. The hepatopulmonary syndrome is characterized by intrapulmonary shunting from arteriovenous communications, which is a generalized feature of chronic liver failure. Hypoxemia may be significant, although routine causes of gas-exchange problems are more common. Renal dysfunction is common and results from diuretic use, intravascular volume depletion, and the hepatorenal syndrome. Azotemia from the hepatorenal syndrome, which is reversible with transplantation, must be distinguished from renal dysfunction resulting from profound hypovolemia, common with aggressive diuretic use and hemorrhage. Endocrine manifestations include glucose intolerance, although hepatic glycogen depletion may lead to chronic hypoglycemia; coagulopathy, resulting from diminished clotting factor production (particularly I [fibrinogen], II [prothrombin], V, VII, IX, and X); thrombocytopenia from hypersplenism and from low production owing to a lack of thrombopoietin; and reduced hepatic clearance of fibrinolysins and tissue plasminogen activators. When end-stage liver disease destroys the normal hepatic architecture, portal hypertension follows, and engorged venous collateral vessels develop in the abdominal and GI tract walls, mesentery, and retroperitoneum. Hemorrhage is common from esophageal varices, and arteriovenous communications contribute to the pathologically decreased systemic vascular resistance and intrapulmonary shunting. [115] The latter leads to intractable hypoxemia, exacerbated by pleural effusions and atelectasis. Ascites develops as a result of chronic venous hypertension, diminished albumin synthesis, and sodium and water retention from unmetabolized aldosterone and antidiuretic hormone. Treatment usually consists of diuretics, which may exacerbate electrolyte and acid-base derangements and intravascular volume depletion. PA hypotension occurs in about 2 percent of patients who present for liver transplantation. [116] Moreover, the hepatopulmonary syndrome, consisting of hypoxemia, pulmonary vasodilation, and hepatic dysfunction, occurs in approximately 30 percent of potential transplant recipients. [116] Currently, outcome studies are being conducted to better define outcome (survival) and costs of performing liver transplantation in patients with these syndromes. [116] Indications and Contraindications The timing of liver transplantation is seldom based solely on objective liver function tests, because these values may not reflect disease severity and vary considerably according to the specific pathologic process. Instead, both medical and social factors are balanced against the ongoing mortality associated with nonsurgical management. [112] Ideally, the procedure takes place before the onset of frank liver failure jeopardizes recovery. Diagnoses in adult liver transplant recipients are listed in Table 55-6 (Table Not Available) . Currently, orthotopic liver transplantation is indicated for nonmalignant end-stage liver disease that will not recur in the allograft, including chronic parenchymal processes (e.g., postnecrotic cirrhosis, Budd-Chiari syndrome, congenital hepatic or cystic fibrosis); acute liver failure (from viral or TABLE 55-6 — End-Stage Renal Disease in Adult Renal Transplant Recipients (Not Available) >From Firestone and Firestone [271] toxin-induced hepatitis, or Wilson disease); cholestatic processes (biliary atresia or cirrhosis, sclerosing cholangitis, or familial cholestasis); and certain inborn errors of metabolism (e.g., primary hyperoxaluria type 1 or familial hypercholesterolemia). [112] The transplantation option is more controversial when recurrence of disease in the allograft is a possibility, in view of the limited donor supply. For example, primary liver and bile duct cancers, as well as hepatic metastases from GI and endocrine tumors, have been treated with liver transplantation with varying durations of remission. [117] But eventual recurrence is the rule, so the procedure is now reserved for those rare cases with highly circumscribed tumors and rapidly deteriorating liver function. Otherwise, if liver function is maintained, hepatic lobectomy is the preferred approach. By contrast, patients with cirrhosis resulting from hepatitis B virus infection, once thought to be an absolute contraindication, have had successful long-term outcomes after liver transplantation [112] despite inability to prevent infection in the allograft. Similarly, results obtained in carefully selected patients with alcoholic liver disease are comparable with those obtained in groups with other liver diseases. [118] Other possible contraindications relate to technical aspects, for example, thrombosis of major abdominal veins, prior portosystemic shunts, or scarring from multiple prior abdominal operations. Moderately advanced age is no longer considered a contraindication, because studies have shown that 5-year survival in recipients older than 50 years of age is similar to that of younger adults. [119] Preanesthetic Considerations Many derangements associated with end-stage liver disease are not correctable until after transplantation. Thus, the major emphasis should be to identify the physiologic systems most seriously compromised and to treat only those that threaten the safe induction of anesthesia. For example, defects in coagulation are usually not corrected at this point, unless there is active hemorrhage or evidence of severe coagulopathy (e.g., prothrombin time [PT] >20 s). Conversely, correction of the coagulopathy may be considered for placement of invasive lines after induction of anesthesia. However, pleural effusions that lead to hypoxemia may on rare occasions necessitate thoracentesis. The timing of transplantation may be critical to outcome in patients with fulminant hepatic failure. Provided patients ——————————————————————————– 1986 have not become deeply comatose, salvage rates can approach 75 percent, [120] which is usually better than that achieved by medical therapy alone. Certain uncommon diseases treated by liver transplantation have additional implications for anesthesiologists. For example, in children with Crigler-Najjar syndrome (bilirubin UDP-glucuronyl transferase deficiency), drugs that interfere with bilirubin- albumin interactions (e.g., barbiturates) should be avoided. Patients with Budd-Chiari syndrome, characterized by extensive hepatic venous thrombosis, may require perioperative anticoagulation. [121] In fulminant hepatic failure, the possibility of cerebral edema in a comatose patient needs to be considered, compared with coma from encephalopathy. Brain injury during transplantation is a real possibility in this situation, and monitoring intracranial pressure perioperatively ought to be considered (Ch. 52) . The potential for active bleeding needs to be considered, as well as appropriate analysis of coagulation and availability of blood products. In addition to standard diagnostic measures, the thromboclastograph has been frequently touted as extremely valuable for liver transplantation. [122] Hett et al [123] have provided an excellent review of this topic. Electrolyte abnormalities, including hyperkalemia and hyponatremia from renal disease or diuretic use, are common, including degrees that would lead to cancellation of almost any other case. Pulmonary hypertension is associated with cirrhosis in a higher incidence than found in the general population. The increased risk of surgery in the presence of pulmonary hypertension depends on the degree of abnormality, but significantly increased morbidity and mortality are likely, as indicated previously. [116] Severe pulmonary hypertension may be a contraindication to transplantation. Screening for pulmonary hypertension is difficult. Symptoms are frequently delayed until the advanced stages of the disease. Echocardiography is the preliminary study of choice, with right-heart catheterization reserved for questionable cases. Because the level of physiologic stress of liver transplantation is extremely high, concomitant coronary artery disease needs to be ruled out (Ch. 25) . Hemochromatosis is a common cause of cirrhosis but may be missed because of secondary reasons for cirrhosis, such as hepatitis C virus infection. Because of frequent GI bleeding and transfusion, standard hematologic test results for hemochromatosis may be inconclusive. Iron overload of the myocardium can lead to significant cardiac dysfunction and can potentially increase the morbidity of liver transplantation. Finally, either as a result of the primary disease process, or of multiple subsequent transfusions, recipients may be seropositive for one or more hepatitis viruses. The anesthesiologist must be aware of the potential for infectious contamination and take appropriate precautions on behalf of the health-care team (Ch. 84) . Induction and Maintenance of Anesthesia The ability to transfuse rapidly is vital to successful outcome in liver transplantation, which involves transection and reanastomosis of several major venous structures (e.g., portal vein and IVC). Typically, at least two large-bore peripheral venous cannulas are inserted prior to induction, one of which is 7.0 Fr to facilitate connection to a rapid transfusion system (see later discussion). Invasive monitoring with systemic and PA catheters is standard in most centers, because major shifts in intravascular volume are the rule, and reperfusion of the allograft can be associated with profound hypotension. [124] Both radial and femoral artery catheters are placed, in that distal arterial flow may be compromised transiently by abdominal aortic clamps during hepatic artery anastomosis. The remainder of the monitoring array is analogous to that used for any critically ill patient undergoing a major surgical procedure. Nevertheless, as sicker patients undergo liver transplantatio n, more sophisticated monitoring is being used by some centers to detect inadequate O2 delivery to organs such as the brain (i.e., transcranial Doppler to determine middle cerebral artery blood flow velocity), [125] heart (i.e., continuous determination of cardiac output), [126] and gastrointestinal tract (i.e., mucosal pH). [127] In addition, transesophageal echocardiography (TEE) is increasingly used (Ch. 31) . Ascites, active GI bleeding, or hepatic encephalopathy may result in delayed gastric emptying. Therefore, aspiration precautions are recommended, and general anesthesia should proceed by either rapid-sequence induction or, in patients with hemodynamic instability, awake endotracheal intubation. Thiopental, etomidate, propofol, and ketamine, supplemented with succinylcholine, have all been used successfully for induction of anesthesia. Plasma pseudocholinesterase levels are typically low in this patient population, but prolongation of the relaxant effect of suc cinylcholine is not of clinical significance. Drugs that do not compromise splanchnic blood flow (e.g., opioids, isoflurane, [128] desflurane, [129] and probably others) are typically used to maintain anesthesia, except in cases of fulminant hepatic failure in which the possibility of intracranial hypertension may contraindicate use of potent inhaled anesthetics. Nitrous oxide is usually avoided due to its potential for bowel distention and increased size of venous air emboli. Liver disease profoundly affects pharmacokinetics, as a result of alterations in hepatic extraction and metabolism, extracellular fluid volumes, levels of serum albumin and alpha1 -acid glycoprotein, and accumulation of bilirubin and other metabolites that displace drugs from protein-binding sites. In general, the net effect of these factors for charged nondepolarizing muscle relaxants is to increase the initial dose requirements and to prolong the duration of action. [130] [131] Newer muscle relaxants, such as cisatracurium [132] and rocuronium, [133] are little affected by liver transplantation (Ch. 12) . Any residual effect is rapidly removed by the newly transplanted liver. [133] In fact, the rate of recovery from vecuronium [134] or rocuronium [135] has been used as a predictor of hepatic allograft function. However, fentanyl and sufentanil kinetics are largely unchanged. [136] [137] Liver allografts rapidly begin to metabolize drugs, [138] but other pharmacokinetic changes (e.g., enlarged volumes of distribution) persist well into the postoperative period. The orthotopic procedure involves total replacement of the diseased native liver with a preserved cadaveric organ, in the most anatomic position possible. Surgery proceeds in three stages: the preanhepatic, anhepatic, and neohepatic (summarized in Table 55-7) . ——————————————————————————– 1987 TABLE 55-7 — Summary of Orthotopic Liver Transplantation STAGE SURGICAL MANEUVERS PHYSIOLOGIC ALTERATIONS Preanhepatic Dissect porta hepatis Acute decompression of ascites Mobilize liver Hemorrhage (venous collaterals) Anhepatic Portal venous clamp Obstruction of venous return Inferior vena cava, hepatic arterial clamp Oliguria (venous congestion) Venovenous bypass (adults) Atelectasis, decreased compliance Retraction on diaphragm Citrate intoxication Neohepatic Inferior vena cava anastomosis Hemorrhage, coagulopathy Flush allograft Hyperkalemia Portal venous, hepatic arterial anastomoses Hypothermia Metabolic acidosis Biliary drainage During the preanhepatic stage, the structures of the porta hepatis are dissected and the native liver is mobilized for removal. Hemodynamic instability is common, due to numerous factors, including acute decompression of ascites, exacerbation of chronic hypovolemia from third-space losses, hemorrhage from venous collaterals in the body wall and mesentery, citrate-induced hypocalcemia, [139] hyperkalemia from rapid transfusion and hemolysis, pericardial effusions rendered significant by hypovolemia, and diminished venous return from abdominal retraction. Hemorrhage may be exacerbated by hemodilution, fibrinolysis, [140] or clotting factor deficiency; differential diagnosis is pursued by means of conventional studies (e.g., PT, partial thromboplastin time [PTT], bleeding time, platelet count, and fibrinogen and fibrin split product levels) and\/or thromboelastography. In addition, endogenous heparin-like substances can impair coagulation. [141] Moreover, reperfusion in particul ar involves release of plasminogen activators that can occur at all stages of liver transplantation, but especially during reperfusion. Drugs such as transexamic acid, aprotinin, and conjugated estrogen have been recommended. [142] epsilon-Aminocaproic acid (Amicar), administered by infusion started prior to incision, may help control hemorrhage secondary to fibrinolysis. At the University of Pittsburgh, a rapid infusion system designed to deliver prewarmed fluids or blood products at a rate of up to 1.5 L\/min is employed routinely (Fig. 55-6) (Figure Not Available) . The device consists of reservoirs, heat exchanger, fluid-level sensors, air detectors, line pressure monitors, and filters integrated Figure 55-6 (Figure Not Available) Schematic of the rapid infusion system developed at the University of Pittsburgh for use during liver transplantation. See text for details. (Courtesy of John Sassano, MD, Pittsburgh, PA.) ——————————————————————————– 1988 to minimize trauma to the formed elements of blood and prevent transfusion of air. Autotransfusion systems that salvage extravasated blood are also used, provided there is no infection or malignancy. [143] Oliguria is common in the preanhepatic phase, and once prerenal causes are eliminated, treatment with potent loop or osmotic diuretics, as well as “renal-dose” dopamine (2 to 5 mug\/kg\/min) is begun. Metabolic acidosis often accompanies hemodynamic instability, particularly with absent hepatic metabolic function. If severe, an infusion of tromethamine [tris(hydroxymethyl)aminomethane] (THAM) or dichloroacetate will avoid the hyperosmolar hypernatremia associated with repeated boluses of sodium bicarbonate. The aggressiveness with which metabolic acidosis should be treated has been controversial in the literature. [144] When the native liver’s blood supply (hepatic artery and portal vein) is transected, and the suprahepatic and infrahepatic IVC is occluded, the anhepatic stage begins. A Sengstaken-Blakemore tube may be placed temporarily if large esophageal varices are jeopardized by IVC occlusion. Venovenous bypass is often used to avoid precipitous decline in venous return a nd cardiac output, as well as venous engorgement in the lower body, bowel, and kidneys. [145] The venovenous circuit reroutes both portal and systemic (femoral) venous blood, extracorporeally, to the axillary vein (then SVC) at 20 to 50 percent normal systemic flow rates. Heparin-bonded tubing obviates the need for systemic anticoagulation. Although venous bypass clearly helps preserve renal function, it has been associated with air and thromboembolism, [146] can prolong the procedure and contribute to heat loss, [147] and does not clearly improve overall morbidity and mortality. [148] Native hepatectomy and allograft implantation require vigorous retraction near the right hemidiaphragm, resulting in atelectasis, hypoventilation, and diminished respiratory compliance. PEEP and augmentation of inspiratory pressure may compensate to some extent. In patients with pulmonary hypertension, sudden cardiovascular depression is more likely. Gillis et al [149] even used manual compression of the abdominal aorta to increase arterial pressure and coronary perfusion in this situation. Citrate intoxication from rapid transfusion is common during this stage, owing to the absence of the liver’s metabolic functions. Rapid transfusion of blood products, especially fresh frozen plasma, which contains the largest amount of citrate, may overwhelm the metabolic activity of the diseased liver. During the anhepatic stage, the complete absence of any metabolism of citrate necessitates the administration of calcium to prevent profound hypocalcemia. Hypotension, which is common duri ng liver transplantation, may be significantly exacerbated by hypocalcemia. Thus, calcium must be supplemented to maintain the ionized level at more than 1.0 mM. Both calcium chloride and gluconate will suffice, even in the absence of the liver. Hyperkalemia, from rapid transfusion, can still be treated in the conventional manner, with glucose and insulin infusion, but metabolic acids, notably lactate, remain uncleared during the anhepatic stage. Even clonidine administration has been recommended to improve fluid requirements and hemodynamic variables. [150] The neohepatic, or postreperfusion, stage begins with reanastomoses of the hepatic major vessels. Prior to unclamping, the allograft is flushed of preservative solution, air, and debris, using portal venous blood. Nonetheless, final removal of the vascular clamps can still be associated with release of a large load of potassium and metabolic acids into the circulation. Hypotension, arrhythmias, and cardiac arrest may follow; inotropic support may be needed to treat myocardial depression from putative cardioactive mediators [151] or venous air embolism. [152] Perhaps the excessive use of antifibrinolytic drugs could contribute to the occurrence of thromboembolism. [153] “Reperfusion syndrome” may cause significant hypotension. The incidence may be 30 to 50 percent. Hypotension occurs within minutes after unclamping the portal vein. Hemodynamically, it is characterized by systemic vascular resistance. Right heart dysfunction has also been described during initial reperfusion. Suggested mediators of reperfusion syndrome include kallikrein-bradykinin syndrome, endotoxin, nitric acid, and prostaglandins. Various predictive approaches (e.g., hemodynamic response to clamping of the IVC, [154] drugs to accelerate graft recovery [155] and avoidance or cardiovascular depressant anesthetics [156] have been recommended with varying degrees of success. Increases in end-tidal nitrogen are useful to distinguish the latter mechanism. Cardiovascular collapse may also be due to pulmonary thromboembolism during reperfusion. [157] [158] [159] With return of allograft function, both metabolic and hemodynamic stability are gradually restored. Urine output typically improves, even in patients with prior hepatorenal syndrome, [150] and inotrope requirements diminish. Clotting variables gradually return to normal, by a combination of specific replacement therapy and production by the allograft. The procedure is completed by biliary reconstruction, either by direct bile “duct-to-duct” anastomosis or by a Roux-en-Y choledochojejunostomy. Postoperative Management and Complications Primary nonfunction of liver allografts is rare since the introduction of the UW solution for preservation. [160] Recovery from primary nonfunction has been reported, but more typically, retransplantation is necessary. [161] Provided allograft function is sustained, metabolic acids including lactate continue to be metabolized and systemic alkalosis may result. Postoperative respiratory complications are common, due to nosocomial pneumonia, diaphragmatic injury, adult respiratory distress syndrome (ARDS) from massive transfusion, and nutritional deficiencies. Thus, pulmonary toilet regimens are of paramount importance. Triple immunosuppression (i.e., cyclosporine, azathioprine, prednisone) is begun immediately in the ICU, yet early rejection episodes are common. Rescue with extra steroid boluses or antibodies (ALG or OKT3) is almost always effective. Other perioperative complications include vascular or biliary leaks, hepatic artery or portal vein thrombosis (particularly in small children), or abdominal abscesses. Longer-term complications include recurrence of hepatitis B or neoplasms, [162] opportunistic infection, and the development of a lymphoproliferative malignancy. Most patients remain intubated and mechanically ventilated in the ICU. Recently, interest in “fast tracking” liver transplant patients has increased efforts at early tracheal intubation. Provided patients are hemodynamically stable, pulmonary gas exchange and mechanics are good, bleeding ——————————————————————————– 1989 and coagulopathy are controlled, and the graft appears to be functioning well, possibly 20 percent of patients may be tracheally extubated immediately at the end of surgery. At two major institutions, major reductions in cost without change in outcome were a result of “fast track” approaches to early tracheal extubation. [163] Special Considerations in Children One-fifth of all liver transplants are performed in children, mostly younger than 5 years of age (Ch. 59) . [164] Overall 1-year survival for the orthotopic procedure in children is comparable to that in adults (i.e., 70-75%), but results are not nearly as good in younger (<3-year-old) and smaller (<12-kg) patients (45-50% 1-year survival). [164] [165] Biliary atresia accounts for a high proportion of preoperative diagnoses, followed by inborn errors of metabolism (alpha1 – anti-trypsin deficiency, glycogen storage disease, Wilson disease, tyrosinemia), and syndromes characterized in part by biliary obstruction (e.g., Alagille and Byler syndromes). Children with biliary atresia have usually undergone a prior decompression procedure (e.g., Kasai choledochojejunostomy), which may complicate both transplant surgery and subsequent biliary reconstruction. Venovenous bypass is limited to patients weighing more than 20 kg, so that oliguria and intestinal complications from lower-bo dy venous engorgement are more common in small children. As with kidney transplantation, oversized liver allografts may lead to blood volume sequestration, profound hyperkalemia after reperfusion, and hypothermia. Peritoneal lavage with warm saline will effectively prevent the last complication. The limited supply of suitably sized donor organs has led to the development of techniques to transplant part of a liver. Reduced-size (“split”) liver allografts enable one donor liver to be used for multiple patients. The method carries with it a significantly higher complication rate, including hemorrhage, [166] organ necrosis, and diminished recipient survival, [165] so it is usually reserved for the desperately ill. In a variation on this theme, living-related (partial) liver donation has been advocated in view of the nearly 50 percent mortality of children waiting for a donor liver. However, there is significant potential for donor morbidity, and considering the relatively reduced survival noted for reduced-size liver recipients, few centers offer this option. Poorer survival among younger and smaller children probably relates to the use of these reduced-sized allografts and to a far greater incidence of hepatic artery thrombosis. [167] Anesthesia After Liver Transplantation The potential for infectious and malignant complications in the post-transplant setting, interactions between immunosuppressants and drugs typically used in the perioperative period, toxicity of immunosuppressants, and special aspects of transfusion in organ transplant recipients have already been considered in detail earlier in this chapter. Liver disease affects pharmacokinetics, and despite a well-functioning allograft, some changes (e.g., enlarged volume of distribution) persist well into the postoperative period whereas others (e.g., hepatic metabolism) return to normal. [168] Early in the postoperative period, the most common reasons liver recipients return to the operating room include exploratory laparotomy for biliary leak or abscess drainage, or open liver biopsy. Ileus or abdominal distention would mandate rapid sequence induction for general anesthesia. Coagulation studies have usually normalized, so regional anesthesia is also a reasonable option. Later, biliary reconstruction procedures are most common. Conclusion Liver transplantation is now a major therapeutic approach to patients with liver disease. As our success and skills increase, sicker patients with more severe liver disease are qualifying as recipients, further challenging our perioperative anesthetic skills. [169]<\/p>\n <\/p>\n <\/p>\n management_of_the_kidney_transplant_recipient_in.10<\/a><\/p>\n hydronephrosis on ultrasound=obstructive uropathy<\/p>\n <\/p>\n Acute occlusion of graft (venous or arterial) occurs within one week posttransplant<\/p>\n Peritransplant hematoma-decreaseing h\/h with increasing creatinine<\/p>\n Great article (Annals EM 2004;44(4):330-341)<\/p>\n Crit Ill Kidney Transplant Pt<\/a><\/p>\n <\/p>\n Pancreas transplantation is considered the treatment of choice for patients with refractory Type I Diabetes Mellitus. The first pancreas transplant was described in 1967 by Kelly et al.<\/a>(pictured) and was performed with a simultaneous kidney transplant in a 28 year old woman with type 1 diabetes. Early efforts were associated with a high complication rate, but this has improved over time. Pancreas transplantation now usually occurs in three settings:<\/p>\n\n
<\/span>Liver Transplant<\/span><\/h2>\n
<\/span>Renal Transplant<\/span><\/h2>\n
<\/h2>\n
<\/span>Pancreas from Renal Fellow BLog<\/span><\/h2>\n