Liver Transplantation A Self-Learning Module For surgical ICU Nurses

University of Rochester Medical Center Strong Memorial Hospital Mar 2002 Karen Parker, RN BSN Linda Plano, RN MS Nasr Anaizi, MS PhD

Table of Contents

Indications for Liver Transplantation Contraindications for Liver Transplantation Manifestations of End Stage Liver Disease Medical Care of the Patient Awaiting a Liver Transplant Nursing Care Priorities for the Patient with ESLD UNOS Listing for Patients Liver Transplantation Child-Turcotte-Pugh (CTP) Scoring System MELD Adult-to-Adult Live Donor Liver Transplantation Post-Operative Nursing Care of the Liver Transplant Recipient Indicators of Post-Transplant Liver Functions Post-Operative Considerations Laboratory Values Differentiating Infection from Rejection Indications for Retransplantation Immunosuppressive Agents and Other Drugs References Self-Assessment Test

Indications for Liver Transplantation

Liver transplantation is indicated for conditions that result in liver cirrhosis, which is defined as irreversible injury to the parenchyma of the liver resulting in widespread fibrosis and nodule formation. The following conditions that are known to lead to liver cirrhosis: Hepatocellular diseases Laennec's Cirrhosis: results from excessive ingestion of alcohol. Cryptogenic Cirrhosis: cirrhosis of indeterminate origin (most likely non-alcoholic steato-hepatitis or NASH). Chronic Hepatitis with Cirrhosis: Autoimmune Hepatitis: a chronic disorder caused by a cell-mediated immune response attaking normal cells of the liver. Chronic Viral Hepatitis: Hepatitis B: transmitted via blood or sexual contact, perinatally, or via percutaneous contamination Hepatitis C: transmitted via blood and possibly sexual contact (<5%). Inborn Errors of Metabolism: Alpha 1 Antitrypsin Deficiency: a1-antitrypsin is an inhibitor of trypsin, an enzyme secreted in inactive form by the pancreas, which breaks down proteins when it is activated in the duodenum. It is thought to account for 10 to 20% of all chronic liver disease in infancy. In adults, a1 Antitrypsin deficiency often manifests as asymptomatic cirrhosis, but can progress to macronodular cirrhosis and may be complicated by the development of hepatocarcinoma. Wilson's Disease: Due to a genetic mutation resulting impaired hepatic excretion of copper; copper accumulates in the liver causing hepatitis and cirrhosis. Hemochromatosis: This is a genetic disorder resulting in altered absorption of iron form the intestine. Excess iron accumulates in the hepatocytes. If this disease goes undiagnosed and untreated, cirrhosis may result. Chemically Induced Liver Damage may be caused by: Phenytoin (Dilantin). Acetaminophen (Tylenol). Isoniazid (INH). Felbamate. Ketoconazole. Carbamazepine (Tegretol). Amanita Phalloides poisoning (wild mushroom ingestion). Certain Herbs (Crotalaria, Senecio, Symphytu, Heliotropium, Senna, Jin Bu Huan, Antracylis, "Chinese Hebal Complex", etc. Others (niacin, nitrofurantoin, valproate, dapsone, azathioprine, ticlodipine, etc). Cholestatic Diseases Sclerosing Cholangitis: an inflammatory process involving hardening and thickening of the tissues along the lumina of the intra- and extrahepatic bile ducts. Primary Biliary Cirrhosis (PBC): a chronic inflammatory process with unknown cause, resulting in fibrosis of the small intrahepatic bile ductules. Secondary Biliary Cirrhosis: occurs due to chronic obstruction of extrahepatic ducts, which could include the common bile duct and its major branches. This may result from several primary causes, some of which could include gallstones, chronic pancreatitis, or primay sclerosing cholangitis. Caroli's Disease: a disorder manifested by recurrent episodes of cholangitis and/or gallstones, resulting from the formation of cystic diations of major intrahepatic bile ducts. Progression to Seconday Biliary Cirrhosis is common. Vascular Disease of the Liver such as hepatic vein thrombosis (AKA Budd Chiari Syndrome) which involves the hepatic vein and blocks hepatic venous outflow. Primary Liver Cancers: Tumors must be small (~<5cm) and not multicentric (can't have >3 foci), and must not extend outside the liver.

Contraindications for Liver Transplantation Sepsis. Malignancies outside the liver. Advanced hepatobiliary malignancy. Active substance abuse. Irreversible brain damage. Inability to comply with post-transplant immunosuppression regimen. AIDS [note that HIV seropositivity does not automatically exclude patients for consideration of a liver tranpslant]. Active cardiopulmonary disease.

Common Manifestations of End Stage Liver Disease (ESLD)
Clinical Signs/Symptoms	Probable Causes
Unstable blood glucose level	Altered carbohydrate metabolism
Fatigue	Altered fat metabolism for energy
Generalized edema	Altered protein metabolism resulting in ¯ albumin synthesis, which is needed to hold fluid in intravascular space (colloid function)
ñ prothrombin time (PT) (ñINR). Tendency to bruise easily. High risk of bleeding.	Altered metabolism of vitamins and iron. ¯ Synthesis of clotting factors and globulin (a protein that plays an Important role in blood clotting). ¯ PLT count d/t persistant hypersplenism
Ascites	Portal Hypertension ( ñ pressure in the portal vein d/t ñ resistance to blood flow through the liver). These patients are at risk for Spontaneous Bacterial Peritonitis (SBP) and may be receiving prophylactic antibiotics (such as ciprofloxacin) to prevent ocurrence of SBP.
GI bleeding	Esophageal varacies, gastric varacies, or hemorrhoids d/t ñ pressure in venous system of GI tract d/t portal hypertension
Jaundice (ñ serum bilirubin)	Inability of the liver to metabolize and secrete bilirubin, the bile pigment which is formed from the breakdown of RBC's
Encephalopathy with ñ serum ammonia (often manifests as irritability & cognitive changes initially but may progress to somnolence and even coma); Asterixis and hyperventilation are also common manifestations of encephalopathy.	ñammonia levels d/t inability of the liver to convert NH3 to urea for excretion.
¯ urine output & (ñ serum creatinine)	Hepatorenal syndrome (¯ renal function associated with hepatic failure; mechanism is not well understood
ñ serum lactate	d/t inability of liver to adequately remove lactic acid (a product of anaerobic metabolism) from blood
ñ serum Alk Phos (alkaline phasphatase)	Excretion of this liver enzyme is impaired with obstruction in the biliary tract
ñ serum GGT (gamma-glutamyl transferase)	Elevation of serum GGT allows for a more definitive diagnosis of obstruction of the biliary tract than the elevation of Alk Phos alone since Alk Phos is also elevated due to damage to extrahepatic tissues (eg. bone). The isolated elevation of GGT has little diagnostic value; GGT level is increased by antiepileptic agents and narcotic drugs.
ñ serum ALT (alanine aminotransferase) (formerly known as SGPT = serum glutamic-pyruvic transaminase)	ALT is found almost exclusively in liver cells. ALT elevation usually indicates liver injury and/or inflammation with lysis of liver cells.
ñ serum AST (aspartate amino transferase) [formerly known as SGOT =serum glutamic-oxaloacetic transaminase)	This enzyme is released into circulation after injury or death to cells. Elevated AST also occurs after an MI.

Medical Care of the Patient Awaiting a Liver Transplant

Treatment of Ascites Restriction of dietary sodium Diuretic therapy: Spironolactone and Furosemide (either drug alone is generally ineffective in these patients). Hypovolemia and electrolyte depletion occurs secondary to over-diuresis and may exacerbate renal dysfunction associated with the hepatorenal syndrome. Paracentesis may be performed to remove ascitic fluid from the abdomen. Close monitoring of the patient's vital signs during this procedure is essential as sudden hypotension and/or tachycardia can occur. A peritoneal venous shunt (Laveen shunt) may be surgically inserted which drains the abdominal cavity into a large central vein. This is not often used due to the significant risk of infection, DIC, or occlusion of the one-way valve used. TIPS shunt: Via an internal jugular vein, the vena cava, and the hepatic vein, a stent is placed within the liver parenchyma. This stent allows for decreased resistance to flow through the liver, connecting the pathway between the portal vein and hepatic vein. This decreased portal pressure helps to prevent further variceal bleeding and accumulation of ascites. Unfortunately, when blood flow bypasses liver parenchyma by passing through this shunt, increased hepatic encephalopathy may occur since the liver is then unable to effectively clear toxins from the blood. Treatment of Variceal Bleeding Fluid resuscitation. Correction of coagulopathies. Sclerotherapy to control hemorrhage. Esophageal variceal ligation (banding). Sengstaken-Blakemore tube: compression device which works by balloon tamponade. Vasopressin or Octreotide therapy. TIPS Distal Splenorenal Shunt (Warren Shunt): The distal splenic vein is anastmosed with the left renal vein. Portal venous circulation is still preserved but decompression of the gastric and esophageal varacies occurs resulting in prevention of re-bleeding. Partial Mesocaval shunt: A small (<15 mm) dacron graft is placed between the superior mesenteric vein and inferior vena cava. This results in partial diversion of portal blood flow away from the liver.

Nursing Care Priorities for the Patient with ESLD

Monitor lab values, especially watching for ¯ BG's, fluid and electrolyte imbalaces (possibly due to fluid retention and treatment with diuretics, malnutrition, and vomiting or diarrhea), ñ coags, ¯ platelet count, and ñ lactic acid. LR is not used with these patients d/t the liver's inability to clear lactate adequately. Monitor for s/sx of bleeding, including checking stools for occult blood. Administer blood products as ordered. Monitor respiratory status and watch for decompensation d/t ascitic pressure on the diaphram or pulmonary edema. Elevate HOB to ¯ pressure on lungs in patient with ascites, and perform PD&C as well as encourage ambulation prn. Monitor I & O and watch for signs of volume overload and administer diuretics as ordered. A low sodium diet may also be ordered. Monitor for encephalopathy. Administer lactulose and/or neomycin as ordered to treat high serum ammonia levels. *At least 3 bowel movements daily is a desired effect of lactulose to rid the body of excess ammonia. A low protein diet may be ordered. Intracranial pressure monitoring may be indicated with risk for cerebral edema. Protect the encephalopathic patient's airway by taking measures to avoid aspiration. OT & PT may be necessary and encourage ROM exercises to maintain existing strength, which may improve the patient's rehabilitation process post-transplantation. Monitor for signs of renal failure. The patient may be on dialysis and possibly CVVHD d/t ¯ BP, in addition to hepatorenal syndrome. Monitor for skin breakdown and apply lotion prn since puritis is common.

UNOS Listing for Patients Liver Transplantation

The Child-Turcotte-Pugh (CTP) scoring system assesses severity of liver disease by assigning scores according to evidence of encephalopathy, ascites, increased serum bilirubinlevels, increased pro-time & INR, and decreased serum albumin levels. This system has recently been replaced by the MELD model, a more objective disease severity assessment tool.

Status 7:   Temporarily inactive but patient continues to accrue waiting time on the transplant list.

Status 3:   Patient requires continuous medical care; Pt. may be followed at home and may require short hospializations that do not result in a change in status; CTP score ³ 7.

Status 2B:   CTP score ³ 10, or³ 7 plus at least one of the conditions listed below: Active variceal hemorrhage. Hepatorenal syndrome. Spontaneous Bacterial Peritonitis (SBP). Refractory ascites/ hydrothorax.

Status 2A:   CTP score ³ 10 and patient is in Critical Care Unit with life expectancy < 7 days and has at least one of the following conditions: Active variceal hemorrhage. Hepatorenal syndrome. Refractory ascites/ hydrothorax. Stage III or IV encephalopathy unresponsive to treatment. The patient can not be a status 2A if at least one of the following exists: extrahepatic sepsis. high dose or 2 or more vasopressors are in use. irreversible multi-organ failure.

Status 1:   Patient has fulminant liver failure with a life expectancy < 7 days or has one of the following conditions: Primary Non-Function of Graft (PNFG) within 7 days post-transplant. Hepatic Artery Thrombosis (HAT) within 7 days post-transplant. Acute Wilson's Disease.

Child-Turcotte-Pugh (CTP) Scoring System For Liver Disease
Points   Þ	1	2	3
Encephalopathy	None	1 - 2	3 - 4
Ascites	None	Slight (or controlled by diuretics)	At least moderate despite diuretic therapy
T. Bilirubin (mg/dL)	< 2	2 - 3	> 3
Albumin (g/dL)	> 3.5	2.8 - 3.5	< 2.8
PT prolongation (secs)	< 4	4 - 6	> 6
INR	< 1.7	1.7 - 2.3	> 2.3
T. Bilirubin for primary biliary cirrhosis, primary sclerosing cholangitis, or other cholestatic liver diseases; these values for bilirubin are to be substituted for the values above.	< 4	4 - 10	> 10

Adult-to-Adult Live Donor Liver Transplantation (LDLT)

Live donor liver transplantation is offered as an alternative to cadaveric donor transplantation to those patients already on the waiting list. Because of the shortage of livers available from cadaveric donors, transplantation from live donors makes it possible for patients who might otherwise die of liver failure while waiting for an organ, to receive a liver transplant. This option also makes it possible for the recipient to be transplanted earlier in the course of their disease which could result in a more successful outcome for that patient. The surgery consists of taking out the entire liver of the recipient and transplanting the right lobe of the donor's liver (~60% of the liver) into the recipient. The right branches of the hepatic artery and portal vein from the donor are connected to the main branches of the recipient. The bile duct of the donated liver is connected to the jejunum. This particular anastmosis of the bile duct is called a choledochojejunostomy or roux-en-y. A turcotte tube will be present in all of these post-operative patients and the same precautions should be taken with the turcotte tube in these patients as in the cadaveric liver recipients. Patients may be considered for live donor liver transplantation when they are already listed on the UNOS listing. They are not taken off the UNOS list if a live donor procedure is scheduled since they will be given a cadaveric liver if it becomes available. If the potential recipient becomes a 2A status or higher on the UNOS list however, they will not be considered for live donor transplantation. It is believed that these very sick patients need a whole liver to survive. The donor's blood type must be compatible with the recipient's, the vasculature of the donor's liver must be normal, and the donor's liver must be of adequate size. (The donor's right lobe should weigh about 1% of the recipient's body weight.) The donor must volunteer to donate the portion of their liver and is considered only after they have notified a transplant coordinator of their decision. The donor participates in an extensive workup prior to the transplant. First, a telephone interview is conducted with a transplant coordinator so that basic information can be obtained and any questions can be answered by the coordinator. Then, the donor is seen in the outpatient clinic where they are interviewed by a transplant surgeon, coordinator, and social worker. An informed consent will be obtained, a hepatologist will obtain a complete history and physical, blood work will be drawn, and an abdominal ultrasound will be performed to assess hepatic blood flow. A psychological evaluation will be performed in order to determine whether the donor is actually volunteering to do this and whether they completely understand the risks involved. For women >35 years old, a pap smear and mammogram is performed and for men >40 years old, a colonoscopy is performed. If there are any idiosyncrasies up to this point or if the donor changes their mind, the evaluation process stops here. More blood tests are done to test for HIV, hepatitis, and for immunology studies. Urinalysis is performed and a pregnancy test is done on females. Liver volume is determined via abdominal CT scan and a chest x-ray, lung function tests, EKG, and Echocardiogram are performed in preparation for the surgery. Angiogram to determine the anatomy of the donor's liver and blood vessels is performed as well. The anesthesiologist will meet with the donor to do a typical anesthesia workup prior to surgery. At any time during this workup, the donor may decide not to go through with it and has the opportunity to stop the evaluation process. Also if a cadaveric liver becomes available during the evaluation process, it is still given to the potential recipient.

Post-Operative Nursing Care of the Liver Transplant Recipient

A. Supplies and Equipment at Bedside Ventilator SvO2 Machine/Calibration Flow Sheet IV pole/IV pumps Additional SA line set-up NS for bolusing Bair Hugger/Blanket Level for transducers NS for C.O. measurements Wrist Restraints SMH 672 Flow Sheet Green Liver Transplant Flow Sheet (may have been initiated on the floor) Urinometer Specimen measuring containers Emergency equipment such as the code cart/Level I Rapid Infuser as is needed. B. Post-operatively, the patient will have the following lines: Two arterial lines. SvO2 Swan-Ganz Catheter and a second introducer. RICC line (large bore line in arm). Peripheral IV (s). May have a Quinton catheter if dialysis was required pre-op. C. The patient will have the following drains/tubes Three Jackson-Pratt Drains T-tube (May also be called a Turcotte Tube, or bile drain) NG tube Foley

JP Discussion: JP A Placement: RUQ under diaphragm, farthest to the left. JP B Placement: Right Side, middle of abdomen near biliary anastomosis. JP C Placement: LUQ under diaphragm The purpose of these drains is to serve as windows to detect any bleeding or biliary leaks. Empty the bulbs as often as is needed to keep them to self-suction (this may be as frequent as every few minutes initially, depending on the amount of bleeding and ascites). However, the physician does at times request that the JP's only be emptied at certain intervals (q2hr, for ex.) in a attempt to allow fluid in the interstitial space to reabsorb into the vascular space. Check with the physician before placing the JP's to wall suction or placing drainage appliances around the JP's. Watch for the drainage to change from bloody to serosanguinous, to serous over the first day or two. You may need to send Hct's on JP drainage to determine the severity of bleeding. Do strip these drains to keep them free of clots. If bile/golden drainage is detected in JP B, the attending physician must be notified immediately as this could indicate a biliary leak. Diagnosis for this leak is made by cholangiogram, ultrasound, or CT, and may be cause for immediate exploratory surgery. However, with split-liver transplants (living donor liver transplant, for ex.), bile may be seen in JP B, and the physicians will simply monitor the patient as usual. T-tube Discussion: If an end-to-end biliary anastomosis (choledochocholedochostomy) is performed, the patient will have a RUQ biliary t-tube drain. This is used to monitor bile production. Document bile color and consistency upon admission and in your q4h assessments. The bile should be a dark golden-brown/dark green color with motor oil consistency. M&R biliary drainage q8h and prn to keep the bile free flowing. Report any changes in consistency, color, or amount immediately to MD. Watery or serous drainage could indicate worsening hepatic function. Secure the t-tube. If the t-tube becomes dislodged, notify the attending physician immediately. This is a surgical emergency. A donor bile duct to recipient duodenum anastomosis (choledochojejunostomy, or Roux-en-y) is performed in the living donor liver recipients and a Turcotte tube (t-tube) is placed in all of these patients as well. A cadaveric liver reciepient may have a choledochojejunostomy and not have a t-tube. Note: Keep the Ioban dressing that has been placed across the patient's chest to secure the t-tube in place. Watch for kinks in the t-tube (especially under breasts), and suspect a kink is there is little bile production.

Indicators of Post-Transplant Liver Functions

Neurological Status If the patient was encephalopathic pre-op, you should observe mental clearing as ammonia levels and cerebral edema decrease. The patient's rate of recovery from anesthesia depends on the amounts and types of agents used, as well as liver and kidney function. Post-op analgesia is usually ordered cautiously so as not to cloud neuro exams. Other considerations include: tremors/seizures/neurotoxic effects of tacro/cyclosporine; intracranial bleeding related to coagulopathy, and; neuromuscular manifestations of electrolyte imbalances (Mg, Phos, Na, Ca, glucose). Neuro status, including pupillary checks, must be done q4h. PT/PTT The patient may have been coagulopathic pre-op, but these lab values should trend towards normal without intervention if the liver is producing clotting factors. Liver Function Tests Albumin, AST, ALT, GGT, LDH, Alk Phos, Total Bili, and NH3 should all begin trending toward normal if the grafted liver is functioning well. Bile Production Ideally, the newly grafted liver should begin to produce bile immediately. Thick, dark, golden-brown/green bile is an indicator of good liver function. Lactate Patients with pre-op fulminant hepatic failure/necrosis should have lactate levels that trend towards normal after transplantation providing their fluid status is adequate. Elevated lactate levels also are seen in hypoperfusion states, late sepsis, or primary non-function.

Post-Operative Considerations

A. Hemodynamics Vasodilation followed by hypotension may occur during the warming phase of hypothermia. Differentiate between hypovolemia and bleeding. Check Hcts. Neosynephrine is generally not used to treat hypotension d/t its vasoconstrictive action which could cause ischemia in the newly grafted liver. Volume/Dopamine may be used based on the patient's cardiac indices/lab values. Hypovolemia may be experienced by the patient d/t third spacing of fluids, hemorrhage, sepsis, low oncotic pressure due to hypoalbuminemia, or complement activation after liver graft reperfusion. This may be treated with volume expanders such as crystalloids (NS = 0.9% NaCl), albumin, or other blood products and as indicated. Use of lactated ringer solution (LR) is avoided as it contains lactate. If the patient's mean arterial pressure (MAP) and urine output remain normal, a lower central venous pressure (CVP / PCWP) may not be treated. The patient is said to be kept "dry." Hypertension may be d/t physiologic stress, shivering, anxiety, pain, hypothermia, tacrolimus or cyclosporine therapy, or fluid overload in patients with renal failure. Fluid overload with an increased CVP/PCWP can contribute to serious post-op complications such as increased risk for variceal hemorrhage, intracranial bleed, dehiscence of the hepatic arterial anastomosis, and increased risk for venous congestion in the newly transplanted liver. Post-op hypertension may be treated with a Nipride drip. Please note: The transplant patient will probably be hyperdynamic as a normal phenomenon of liver disease. They may have a CO as high as 15 L/min with an SVR in the 200-400 range. These numbers are normal for a post-op liver transplant patient and are not treated. If the patient has a low CO (<2.0), consider cardiac tamponade, cardiac effusion, tension pneumothorax, myocardial ischemia and possible MI. B. Respiratory Status Extubation may be delayed by: Right hemidiaphragm paralysis d/t surgical damage to the phrenic nerve Lung expansion/ventilation compromise d/t ascites, pulmonary edema, atelectasis, and the high incidence of pleural effusions, causing decreased compliance of the lungs. Oxygenation may be compromised by bacterial, viral, or PCP pneumonia, smoking history, atelectasis, or ARDS. Higher pre-load levels aimed specifically at preserving renal function. Please Note: The intubated, mechanically ventilated post-op liver transplant patient will be weaned as tolerated per orders. Occasionally, some of these patients may have extended intubations. Pulmonary toilet post-extubation is essential in preventing post-op respiratory complications. Do assist the patient with turning, C&DB, using IS, and getting OOB. C. GI and Nutrition Assessment of the patient should consider the possibility of: Malnutrition d/t pre-existing liver failure. Nutrition given via HAL/tube feeds/po. Monitor Albumin and prealbumin levels. These are usually low in liver patients. Contact Nutritional Support Services to consult. Ileus. Treatment: NG left in place, especially with Roux-en-y Procedure. Peptic ulceration d/t steroid therapy and stress. Prophylactically given Pepcid. Re-bleeding from varices if graft fails. Treatment may consist of use of Blakemore tube, IV vasopressin, IV NTG, and monitoring gastric pH with treatment as ordered. Bowel perforation d/t ulceration, colitis, anastomosis bleeding at Roux-en-y site. Acute Abdomen d/t SBO, perforation, peritonitis, pancreatitis, hemorrhage, and biliary leak. Assess for signs of acute abdomen, including tenderness, firmness, distention, fever, increased WBC count, or JP drainage changes. Diarrhea: (iatrogenic) d/t lactulose, antacids, antibiotics, or high osmotic loads from enteral feedings. Check for c. diff, parasites, and leukocytes. D. Renal Status Patients who experience renal insufficiency/failure pre-op in conjunction with ESLD have what is known as hepatorenal syndrome. Risk factors for continued post-op renal problems are: Nephrotoxic drugs: Cyclosporine, Tacro, Abelcet, aminoglycosides, etc. Intra/post-operative instability coupled with hypoperfusion. Recurring hepatorenal syndrome related to primary nonfunction or acute liver failure. Please Note: Inquire about renal dose for medications when you observe increasing BUN/Cr levels. Elevating BUN/Cr are good indicators of worsening renal insufficiency and impending renal failure. In addition, BUN can also be elevated by dehydration and reabsorption of blood in the GI tract. Do draw Cyclosporine/Tacro trough levels daily so that doses can be adjusted to obtain non-toxic, yet therapeutic levels. Do monitor urine output q1-2h. These patients may require low-dose Dopamine or Cardene to promote adequate urine output. E. Dermatology Incisions: A "Mercedes Benz" incision will consist of a transverse incision across the entire upper abdomen, split by a vertical midline incision up toward the xiphoid process with staples and an OR dressing. An abdominal binder may be used to ease the DSD change and decrease the use of tape. Cutdown or precutaneous sites where the veno-venous bypass pump was inserted are usually found in the left axilla and right groin. These areas have DSD's. Do give good wound care and be highly observant for infections as these patients are immunosuppressed. Poor skin integrity related to pre-op malnutrition. They may have pruritis which may respond well to Sarna lotion. They are often subject to skin tears. These patients tend to ooze serous fluid from any skin breaks d/t low serum albumin levels. Protection of the skin includes sheepskin booties, turning, and keeping the skin as dry as possible. Air mattresses may also be used.

Laboratory Values

The green liver transplant flow sheet is prominently posted in the patient's room. Daily lab values, temp, weight, drug levels, anti-rejection drug regimens and doses are recorded here. Observation of trends can be easily visualized by the health care team. It is preferential to concentrate on trends rather than absolute values of most labs. Hyponatremia: Often caused by remobilization of free water. Tx: To be corrected slowly (central pontine myelinolysis) with fluid restriction. Hypernatremia: Occurs with dehydration, diuretics, salt-rich solutions (albumin). Tx: Rehydrate, decreased / discontinue diuretics, mix albumin in D5W instead of the usual NS. Hypokalemia: Seen with diuretic usage, metabolic alkalosis, insulin drip therapy, steroid therapy, hypothermia, use of Ampho B. Tx: Potassium supplements. Hyperkalemia: May occur as a result of renal failure, Primary Nonfunction of Graft (PNFG), multiple blood transfusions, or as a side effect of Tacro or Cyclosporine. Tx: If acutely high, may require insulin/glucose regimen, Kay Exlate, or dialysis. Hypomagnesemia: Related to hypocalcemia, Cyclosporine/Tacro side effects. Also lowers the threshold for seizures and other neurotoxic side effects of Tacro and Cyclosporine. Tx: Magnesium supplements. Hypocalcemia: May be the result of massive blood transfusions. Necessary in the intrinsic clotting cascade. Tx: Calcium supplements. Hypophosphotemia: Weakens respiratory muscles, adversely effecting ventilator weaning. Causes neuromuscular irritability and contributes to platelet dysfunction. Tx: Phosphate supple-ments. Severe hypophosphotemia requires IV phosphate. Hyperphosphotemia: Related to renal failure. Tx: Phosphate binders (CaCO3), or dialysis. Hypoglycemia : Recurrent acute liver failure, PNFG. Tx: Dextrose IV may be necessary based on blood glucose levels. Hyperglycemia: Immediately post-op is considered a good sign of glycogen storage and gluconeogenesis by the grafted liver. May also result from steroid therapy or sepsis later in the post-op phase. Another cause may be the diabetogenic effects of Tacro therapy. Tx: Insulin drip per protocol or sliding scale. PT/INR: May be grossly elevated post-op. Should begin to normalize. A PT < 20 usually is not treated unless the patient is actively bleeding. PTT: May be grossly elevated post-op. Should begin to normalize. Not treated unless patient actively bleeding/invasive procedures will be performed/MD discretion. Hct : Monitor for post-op bleeding. Every drop of 3 points is approximately a unit of packed RBC's. As coagulation normalizes, the Hct will become stable. WBC: May be affected by steroids and other immunosuppressants, and infection. Monitor for abnormal values. Platelets: Will be treated for <20,000 if patient is actively bleeding.

Differentiating Infection from Rejection

Transplant patients may experience infection and rejection simultaneously. The patient's response to changes in antibiotic and immunosuppression therapy guides medical decisions regarding the patient's care and ultimately impacts on the survival of the grafted liver. It is imperative to carefully and accurately transcribe and administer changes in medications. The signs and symptoms of rejection mimic those of infection with a few variations. Both can cause hepatic dysfunction, yet their treatments are completely different. When rejection is suspected, it is important to rule out infection, as well as technical causes for the hepatic dysfunction. Signs/Symptoms of Infection Signs/Symptoms of Rejection fever fever ò quantity/quality of bile ò quality/quantity of bile ñ LFT's ñ LFT's malaise malaise increased ascites increased ascites   graft site tenderness To differentiate between these two phenomenon, a series of steps may be taken. The patient may be: Pancultured for a temperature ³38.2 to attempt to isolate an infectious etiology of the symptoms present. (Maximum of one work-up in a 24 hour period). Doppler untrasound performed to establish if there is a vascular etiology for the hepatic dysfunction. Cholangiogram done to establish if there is a biliary etiology for the hepatic dysfunction. Dilatation or surgical repair/revision of the biliary anastomosis may need to be performed based on the results of the test. Liver biopsy will be done if definitive diagnosis of rejection is needed. Common Infections: Bacterial Infections may be caused by line sepsis, infected peritoneal fluid, pneumonia, intra-abdominal abscess, biliary anastomotic leak, UTI, or cholangitis secondary to biliary tract obstruction. Specifically, staph aureus sepsis may occur from line infections. Potential opportunistic infections such as pneumocystis carinii pneumonia (PCP) may be prevented by giving Bactrim po or Pentamidine inhalation prophylactically. Potential Fungal Infections as Candida Albicans are prophylactically treated post-op with fluconazole or Nystatin swish/swallow. Aspergillus/Mucor may also occur. Potential Viral Infections such as Cytomeglovirus (CMV) and Herpes Symplex Virus (HSV) are prophylactically treated with gancyclovir or valacyclovir . Other viruses that may be encountered are Epstein Barr Virus (EBV), which is responsible for post-transplant lymphoproliferative disorder. There are 4 types of Rejection that can occur: Hyperacute rejection occurs minutes to hours after transplantation secondary to presensitization (humoral response). This process is acute and rare. Total hepatic failure results, and immediate retransplantation is required. Accelerated, or subacute rejection is cell mediated, and occurs 2-4 days post-op. It is recognized by fever, worsening LFT's, jaundice, decreasing quality/quantity of bile, malaise, clay-colored stool, tea-colored urine, and RUQ pain. Acute rejection is also cell mediated, with the same symptoms as accelerated rejection. It is seen 7 days to several weeks post-op. Chronic rejection is a combination of cell mediated and humoral responses. It can occur months to years post-transplant. Progressive jaundice, malaise, and gradual increasing levels of Alk Phos, GGT, AST, ALT, and bilirubin levels are seen. Please note: The type of rejection is based on timing after transplant, lab values, types of symptoms, and results of the liver biopsy. Most patients remain relatively stable throughout rejection episodes. Rejection can, however, cause a patient's condition to rapidly deteriorate, accompanied by massive ascites, hemodynamic instability, hepatic dysfunction, and renal failure. If these patients fail to respond promptly to antirejection medications, retransplantation may be necessary. Please refer to the pharmologic agents for the treatment of rejection.

Indications for Retransplantation

Primary Non-Function of Graft as manifested by failure to regain consciousness, hemodynamic instability, poor quality/quantity of bile, increasing PT, renal dysfunction, rise in transaminases and bilirublin, lactic acidosis, and persistent hypothermia. Acute Hepatic Artery Thrombosis as noted by increased levels of transaminases, fulminant hepatic failure, and sepsis with hepatic abscesses or gangrene of the liver. This is diagnosed by doppler ultrasound and/or arteriogram. Portal Vein Thrombosis as seen by rapid deterioration of the patient's condition including massive ascites, renal failure, hemodynamic collapse, and profound hepatic dysfunction. Acute Rejection Refractory to Pharmacologic Treatment resulting in worsening hepatic function and declining patient condition from diagnosed rejection despite full pharmacologic intervention.

Immunosuppressive Drugs

Tacrolimus (aka Prograf, Tacro, or FK506) Action: Calcineurin inhibitor: blocks interleukin-2 (IL-2) production, ultimately preventing production and activation of cytotoxic T-cells; 10-100 times more powerful than Cyclosporine. Side Effects: Neurotoxicity manifested by confusion, aphasia, tremors, headache, insomnia, photophobia, seizures. Nephrotoxicity manifested by elevated BUN/Cr (d/t decreased glomerular filtration), hyperkalemia, hypomagnesemia. Also hyperglycemia, thrombocytopenia, leukopenia, diarrhea, hepatotoxicity, and hypertension. Uses: Mainly to prevent acute rejection. Occasionally, higher doses are used as rescue therapy to help reverse an ongoing episode of acute rejection. Please Note: Tacrolimus is available as a suspension made in the Pharmacy. You should use this formulation for patients who are not able to swallow the capsule. Oral tacrolimus is administered at 8am and 8pm unless otherwise instructed by the attending. Tacrolimus levels are drawn around 7:30 q am before each morning dose is given. One lavender top tube is sent to Chem. The target blood tacrolimus levels vary depending on the specific condition of the individual patient and range between 5 and 15 µg/L; levels ³ 15 µg/L may be needed in instances of acute rejection, but should not exceed 18 µg/L. Tacrolimus absorption may be decreased when administered with magnesium salts and antacids. Separate administration of tacrolimus from these substances by at least 2 hours. click here for more detail Cyclosporine (Neoral, Gengraf) (CSA) Action: Calcinuerin inhibitor - blocks interleukin-2 production, ultimately preventing production and activation of T-cells. Side Effects: Nephrotoxicity (ñ BUN/Creat.), Hyperkalemia, hypomagnesemia, tremors and seizures that are worsened by hypomagnesemia, hypertension, gingivival hyperplasia, hisuitism, and hepatotoxicity. Uses: Prevention of acute rejection. Please Note: Oral cyclosporine is administered at 8am and 8pm. CSA levels are drawn around 7:30 q am before each morning dose is given. One lavender top tube is sent to Chem. The target level for CSA is 100-400 µg/L. click here for more detail Sirolimus (Rapamune) (previously known as rapamycin)[aka Rapa] Action: inhibits mammalian target of rapamycin (mTOR) resulting in suppression of T-cell proliferation. Acts synergistically with calcineurin inhibitors (CSA or Tacro) Side Effects: ñ cholesterol, ñ triglycerides, HTN, interstitial pneumonitis, thrombocytopenia, anemia, arthralgia, acne, rash, URI, insomnia, tremor. ñ risk of infection (e.g., CMV), ñ risk for lymphoma, Uses: used as immunosuppressive adjunct with CSA and steroids; may also be combined with tacro instead of CSA. Please Note: Sirolimus administration should be 4 hours after CSA administration. (Sirolimus may, however, be taken at same time as tacro). Sirolimus solution is to be mixed only with water or O.J.; Æ paper or styrofoam cups. click here for more detail Mycophenylate Mofetil (MMF, Cellcept®) Action: inhibitor of DNA/RNA synthesis, thereby suppressing lymphocyte proliferation and antibody production. Uses: immunosuppression in combination with tacro or CSA and a steroid. Side Effects: GI upset, Diarrhea, constipation, drug-induced fever, peripheral edema, hematuria, acne, dyspnea, cough, infections, headache, back pain, chest pain, insomnia, dizziness, tremor, anemia, leukopenia, thrombocytopenia, leukocytosis. Please Note: If MMF is administered through the NG/FT/PO route, it should be separated from oral calcium or magnesium salts by at least 2 hrs. If MMF (Cellcept) is given via the IV route, it is important to know that the injectable form is stable for only a limited time once prepared so pharmacy must be notified ~1 hr prior to when the next dose is due so they can prepare it. click here for more detail Corticosteroids The steroids most commonly used as immunosuppressants are methylprdnisolone (MPred or Solu-Medrol) for IV USE and prednisone for oral use. Action: Steroids possess generalized, nonspecific antiinflammatory and immunosuppressive actions whose mechanisms are only partially understood. Steroids easily penetrate the cell membrane of lymphocytes and interfere with the production of several interleukins, blocking T-cell proliferation. Uses: Induction of immunosupprssion (1 gram or 10 mg/kg of MPred given as a bolus dose in the OR immediately before transplant). Treatment of acute rejection (1 gram of MPred IV qday up to three doses). The bolus doses are usually followed by a gradual steroid taper regimen lasting 2 to 3 weeks. Side Effects: Bleeding ulcers, hyperglycemia, neurotoxicity, mood swings, infection, poor healing, osteonecrosis, hypertension, obesity, pancreatitis. click here for more detail Azathioprine (Imuran) Action: Anti-proliferative, anti-metabolite immunosuppressant. It inhibits DNA/RNA synthesis interfering with both cell-mediated (T-cells) and humoral (B-cells) immunity. Side Effects: bone marrow suppression (thrombocytopenia/leukopenia), hepatotoxicity, hair loss, skin fragility. Uses: Prophylaxis from rejection. May be used in conjunction with Tacro OR cyclosporine OR as a substitute if needed in combination with steroids. click here for more detail Muromonab CD3 or OKT3 (Orthoclone®) Action: a murine-derived monoclonal antibody directed against a specific antigen on the T-cell surface. Uses: OKT3 is used mainly as rescue therapy for acute rejection. It may also be used as induction therapy. Tacro, CSA, or Cellcept should not be given with OKT3 without the express orders of the transplant attending. Side Effects: ACUTE CARDIOPULMONARY COLLAPSE presenting as an anaphylactic-like reaction. Usually manifests with the firsts two or three doses. PATIENT MUST BE PRE-MEDICATED WITH TYLENOL, BENADRYL, AND A CORTICOSTEROID PRIOR TO EVERY DOSE. Other side effects include tingling of hands and feet, headache, and sterile meningitis. click here for more detail Thymoglobulin (Anti-Thymocyte Globulin, rabbit) It's an immune globulin product obtained from rabbits immunized with human thymocytes. Action: T-cell depletion achieved through opsonization and complement-assisted, antibody-dependent cell-mediated cytotoxicity. Damaged T-cells are cleared by lymphoreticular system. Uses: Induction of profound immunosuppression starting immediately before transplantation, especially in patients with marginal or poor renal function and who are not expected to tolerated the calcineurin inhibitor well. Reversal of acute rejetion, especially steroid-resistant rejection Thymoglobulin® has been shown to be superior to ATGAM and OKT3 Side Effects:Infusion-related reactions including fever, chills, hypotension, ñ HR, dyspnea, chest pain,¯ BP, ñ BP, ñ K, asthenia, edema, leukopenia, thrombocytopenia, anemia, anaphylaxis, N/V, diarrhea, stomatitis, GI bleed, myalgia, seizures, infection. more detail IL-2-Receptor Antagonist Antibodies The antibodies are products of recombinant DNA technology, and include daclizumab (Zenapax) and basiliximab (Simulect). Action: inhibit IL-2 interaction with T-cells, which results in decreased proliferation of activated T-cells. Side Effects: data very limited at this time; watch for hypersensitivity reactions especially with Simulect. Uses: Mainly as induction immunosuppressive therapy given immediately before and after the transplant operation. click here for more detail

Miscellaneous medications

Alprostadil (Prostaglandin E1 or PGE1) Action: PGE1 may improve hepatic blood flow, reduce postischemic reperfusion injury of the liver, and prevent primary non-function of the graft. It may enhance immunosuppression and help prevent rejection. It may also improve renal perfusion/function. PGE1 causes vasodilation and inhibition of leukocyte adhesion as well as inhibition of platelet aggregation. Uses: Started on the liver transplant patient ASAP after restoration of blood flow and continued throughout the ICU stay. Side Effects: flushing, hypotension, tachycardia, cardiac arrest, DIC, thrombocytopenia, anemia, fever, headache, dizziness, seizures, apnea, cough, nasal congestion, and diarhea. Please Note: Begin IV infusion at 0.1 mcg/kg/hr, ñ q hr by 0.2 mcg/kg/hr to max. rate of 0.6 mcg/kg/hr, or per order. Monitor BP (titrate for MAP ³ 70), and monitor PLT count (notify M.D. if PLT < 50). Discontinue when ordered by cutting rate by half q 2hr x 2, then stop infusion. (First ¯ should occur in the ICU, but the gtt may continue to be D/C'd on the floor.) more detail Aprotinin Action: antifibrinolytic and protease inhibitor: "...has been demonstrated to reduce hyperfibrinolysis and intraoperative relase of tissue-type plasminogen activator in patients undergoing orthotopic liver transplantation." (Micromedex ® Healthcare Series, 2000) Uses: administered as an IV drip to the liver transplant recipient during and immediately following the operation. Side Effects: thromboembolism, tachycardia, and bronchospasm; watch for hypersensitivity reaction. Please Note: Aprotinin is usually started immediately after induction of anesthesia and administered continuously until the procedure ends, but has been known to be ordered to continue infusing in the ICU for a short time period following arrival to the unit.