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26 Critical care of the liver transplantrecipientMarkus Béchir1, Erik Schadde2 and Philipp Dutkowski2

Swiss HPB and Transplantation Centers, Section of Intensive Care Medicine1, and Department of Surgery 2, University Hospital Z ürich,Zürich, Switzerland

Introduction

LT is a highly standardized operative procedure and has been recognized as a valuable treatment option for many patients with end -stage liver disease. In spite of numerous improvements in organ procurement, preservation, and implantation techniques, one key factor for reliable outcome after LT remains pro-fessional intensive care treatment in the direct postoperative course. Because artifi cial liver support is still not reliable as a bridge for transplant failure, recipients are dependent on immediate graft function after transplantation. While a liver transplant recipi-ent with a low Model of End -stage Liver Disease (MELD) score and a standard liver graft usually will develop suffi cient liver metabolism already shortly after transplantation and thus only needs a short stay in an intensive care unit (ICU), the requirement of

Medical Care of the Liver Transplant Patient, Fourth Edition. Edited by Pierre-Alain Clavien, James F. Trotter.© 2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

advanced intensive care is high in those liver transplant recipients who are already extremely sick before trans-plantation. This risk appears to be even more increased if extended -criteria donor (ECD) liver grafts are used, as is often necessary today due to the severe shortage of organs. The most feared complications in such cases are septic in nature and deserve careful evaluation. This chapter will summarize the current methods for assessment of graft function after LT, list management of common medical and surgical complications and of nutrition, and review the currently available predic-tion models for risk evaluation before LT.

Assessment of graft function

The function of a transplanted liver depends on graft quality, procurement and storage conditions, and

Key learning points• Early extubation and careful assessment of pulmonary hypertension minimize pulmonary morbidity. • Persistent acidosis, lack of liver function and persistent transaminitis should trigger immediate evaluation of the

hepatic artery and raise concern about primary nonfunction or initial poor graft function. • Estimation of renal risk based on preoperative assessment, judicious use of simultaneous liver –kidney

transplantation and use of nephroprotective intraoperative strategies help to reduce renal dysfunction. • Delirium is the most common psychiatric complication and its etiology includes infection, calcineurin inhibitors,

and pre -existing encephalopathy. • Biliary complications have to be recognized early to reduce infectious complications. • Hepatic artery thrombosis (HAT) is the most feared surgical complication and HAT within the fi rst days requires

retransplantation.• Most donor and recipient scoring systems for prediction of morbidity after liver transplantation (LT) are unreliable.

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evidence-based guidelines for the recognition of graft dysfunction in LT do not exist. One of the fi rst indications of graft function is the hepatic bile fl ow during implantation, often documented by the surgeons. Another point is the clearance of anesthetic agents in the immediate postoperative period by clinical neurologic assessment. It is important to |withhold sedation until the patient ’s liver function is established in the ICU. While some degree of

recipient factors. Feng et al. performed an analysis on donor risk factors in LT and found that 1 -yearmortality depends on seven donor risk factors, includ-ing: 1) age, 2) race, 3) height, 4) cause of death, 5) donation after cardiac death status, 6) cold ischemia, and 7) partial graft status, resulting in a comprehen-sive donor risk index (DRI) for liver grafts. 1 Along the lines of the increased mortality and morbidity, a prolonged stay in the ICU can be expected. However,

Figure 26.1 Multidisciplinary aspects after liver transplantation

Renal

Septic shock

Neuropsychiatric

Cardiovascular

Pulmonary

Issues in

Critical Care Management of

Liver Transplant Recipients

nephrotoxicity

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In general, dynamic liver tests are related to the ability of the liver to metabolize or eliminate defi ned substance. For example, the capability of the liver to exclusively eliminate indocyanine green (ICG) into the bile without enterohepatic recirculation can be analyzed. Importantly, the plasma disappearance rate (ICG -PDR) is not only dependent on biliary excretion but also on blood fl ow and hyperbilirubine-mia, and short -term changes in ICG -PDR may refl ect changes in blood fl ow rather than hepatocellular function.4

Another dynamic liver test is the monoethylgly-cinexylidine test (MEGX), based on the hepatic conversion of lidocaine to MEGX, which is related to the cytochrome P450 system. In contrast to ICG -PDR, the MEGX test does not allow beside assessment since it requires immunoassays or chromatograhic analysis. The results have to interpreted in relation to other substances that interfere with the cytochrome P 450 system like antibiotics, immunosuppressive agents or antidepressants. 4

The LiMAx test is a newly developed bedside test based on the hepatocyte -specifi c metabolism of the C13-labelled substrate (methocetin) by the cytochrome P450 IA2 isoenzyme. 5 Recently, initial graft perform-ance measured by the LIMAx test at day 1 was closely associated with early post -transplant outcome. 6 Clear threshold values for reliable separation of primary nonfunction and delayed graft function, however, are not yet available.

Medical complications

Sepsis

Patients undergoing LT may have undetected previous infections, therefore all previous antibiotics and colo-nization patterns should be investigated prior to transplantation. In high -risk patients, as for example in cholestatic liver diseases (primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC)), or retransplantations, a culture of the cut surface of the bile duct at the time of transplant is helpful to guide further antibiotic administration. Since bacte-rial translocation is a possible etiology for bacteremia, some investigators have proposed that probiotic therapy prevents infections in liver transplant recipi-ents. In this context Rayes et al. reported that early enteral nutrition supplemented by lactobacillus and

preservation injury and elevated liver enzymes are observed in every liver transplant, coagulation parameters and transaminases (alanine aminotrans-ferase (ALT) and aspartate aminotransferase (AST)) should improve continuously after LT. However, the level of liver enzymes does not correlate with liver function at all, therefore most centers rely on assess-ment of INR and factor V, analyzed every 6 h after transplantation within the fi rst 2 d. Coagulation threshold values for the defi nition of primary nonfunction or delayed graft function do not exist, but generally primary nonfunction has been defi ned as the combination of poor bile production, hypoglycemia, coagulopathy, encephalopathy, renal dysfunction, elevated transaminases and shock, leading to retransplantation or death within 7 d after transplantation. Any lack of neurologic stability, increasing hemodynamic instability and noncorrec-tion of the INR and or factor V in the presence of patent vascular supply by ultrasound is suspicious for primary nonfunction and the patient might have to be relisted. The application of fresh –frozen plasma or coagulation factor concentrates bears a risk of masking the actual liver synthetic function and can only be recommended once the defi nitive decision for retransplantation is made.

Liver assist devices are rarely available and gener-ally worsen coagulopathy. If the patient becomes more unstable and cannot be managed with conven-tional means, the patient may need an allograft hepatectomy and portal -caval shunt in order to preserve his candidacy for retransplantation.

Even more diffi cult is the recognition of those cases with delayed graft function, where no retransplant is necessary due to the fact that liver graft function recovers after 2 –3d. The distinction between primary nonfunction and delayed graft function requires, therefore, repeated assessment of all biochemical and clinical parameters. Ploeg et al. defi ned delayed graft function by the combination of serum AST >2000U/L,prothrombin time <16s and amomonia >50μmol/Lduring the postoperative days 2 –7.2 A more recent defi nition from 2010 is based on the presence of least one of the following parameters 7 d after LT: serum bilirubin ≥10mg/dl, INR ≥1.8 or ALT >2000U/L.3

Beside static tests of liver function, such as serum activities of liver enzymes, protein synthesis and bilirubin, several dynamic tests have been developed to better stratify risk candidates for graft failure.

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The most important risk factor for postoperative renal dysfunction is pretransplant dysfunction. The Model for End -stage Liver Disease (MELD) score includes kidney function (creatinine) as an important parameter along with international normalized ratio (INR) and bilirubin. Because liver grafts are currently allocated by the MELD system in many countries, numerous candidates for liver transplantation present today with impaired kidney function already before transplant. The differentiation between chronic kidney disease and acute pre -transplant renal injury due to hepatorenal syndrome and acute tubular necrosis can be diffi cult and involves ultrasound, urinary electrolytes, urinary sediment analysis, and biopsy. Biopsy data have demonstrated that chronic structural changes are seen in liver transplant patients with normal creatinine, and are more common than suspected at least in the large group of patients with hepatitis C. 9 In patients needing hemodialysis for more than 8 weeks prior to LT, a combined liver –kidney transplantation should be discussed.

It has been assumed that the prevention of early AKI begins in the operating room. Meticulous surgery with avoidance of blood loss, short anhepatic phase, and minimization of adrenergic agents may mitigate renal injury. Some studies have further suggested that using partial caval clamping (i.e. “pig-gyback technique ”) has less risk of hemodynamic instability and AKI, but evidence by larger rand-omized studies is clearly lacking. 10 Renal risk is likely additive in the postoperative period and the use of known nephrotoxins (e.g. aminoglycosides) should be avoided. There is no clear consensus whether the use of drugs such as prostaglandin E1, intraoperative diuretics, N -acetylcysteine, sodium bicarbonate, or fenoldopam have a nephroprotective effect during or after surgery. Randomized studies will be needed to test pharmacologic intervention to protect renal function.

Postoperative AKI may be reduced by limiting reoperations and early recognition of infections. Calcineurin inhibitors for immunosuppression can be decreased by the combination with interleukin 2 inhibitors and/or mTOR inhibitors. In spite of the fact that LT may correct hepatorenal syndrome, temporary renal replacement therapy (RRT) is currently needed in many cases because impaired kidney function already exists pre transplantation in numerous recipients. Most kidneys recover with time

fi ber reduces bacterial infection rates following LT. 7

Deep surgical space infections and biliary infection are other common bacterial infections. 8 As a rule, all potential sites for infection should be explored and, if possible, eliminated (catheters, hematoma, or abscess-suspicious fl uid collection). The threshold for surgical re -exploration is therefore low, if the source of infection cannot be determined by imaging and culture.

There are data supporting the use of activated protein C in liver transplant patients with septic shock. There is currently no good algorithm guiding management of immunosuppression in infection and septic shock, however patients will likely die from infection, not from rejection. Consequently, cal-cineurin and mTOR inhibitors and antiproliferative agents have to be reduced in severe sepsis.

While the risk of bacterial infections remains high after LT, the risk of fungal infections is <5%8 in the standard case. This is different if small bowel perfora-tion or biliary leaks occur, which generally require antifungal treatment. The majority of fungal infec-tions are due toCandida species. A recent meta -analysisrecommends prophylaxis for subgroups of patients who have been shown to be at high risk for fungal infection including those: 1) with acute liver failure, 2) who have undergone re -transplantion, 3) who experience large blood loss, 4) with acute renal failure, 5) requiring hemodialysis, and 6) requiring re-operations for complications. Because infections occur mainly in the fi rst months after transplantation, prophylaxis should be continued for 2 –6 weeks after transplantation. In most centers, prophylaxis for Candida species with fl uconazole at a prophylactic dose will be considered suffi cient. However if fl uconazole -resistant Candida species are proven or even an Aspergillus infection is detected, either liposomal amphotericin -B solutions or echinocandins such as micafungin should be used.

Renal dysfunction

The incidence of acute renal failure after LT varies largely in the literature, ranging between 27 and 67%. The Acute Dialysis Quality Inititative work-group has proposed a multilevel classifi cation system for acute kidney injury (AKI) using the acronym RIFLE ( Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease).

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A low cardiac index after LT with signs of systemic hypoperfusion (reduced glomerular fi ltration, acido-sis, delirium, liver graft dysfunction) could also be due to cirrhotic cardiomyopathy or to the cardio-myopathies associated with alcohol, hepatitis or hemochromatosis. Preoperatively cardiac decompen-sation is often absent because the cardiac workload is reduced through systemic vasodilation associated with advanced liver disease.

The majority of low cardiac output states in the ICU after LT are most likely caused by postoperative pulmonary hypertension with or without a compo-nent of right heart dysfunction. This condition is especially problematic since it adds to venous graft congestion and dysfunction, the hemodynamic problem of low cardiac output, and arterial hypoper-fusion of the transplanted liver. The experience from the Baylor Transplant Center and Mayo Clinic Rochester confi rmed that mortality after LT for pati-ents with mean pulmonary pressures of >35mmHg(“moderate pulmonary hypertension ”) is prohibi-tive.14,15 The authors of this chapter follow the Baylor algorithm, which dictates that these patients should be treated with epoprostenol therapy. These patients may be active on the list as long as mean estimated pulmonary arterial pressure (PAP) on screening echocardiography remains <35mmHg. These patients should be called in for liver transplantation with a backup. Intra -operative vasodilator therapy with epoprostenol, inhaled nitric oxide and restrictive volume management are usually initiated to improve cardiopulmonary fl ow and avoid right heart decom-pensation, especially during the reperfusion phase. This treatment needs to be continued on ICU.

Recently the liver transplant anesthesia consortium (LTrAC) surveyed international and US transplant programs and found that 85% of US programs and 65% of international programs use the pulmo-nary artery catheter (PAC, Swan –Ganz catheter) for monitoring, whereas intraoperative transesopha-geal echocardiography (TEE) is less common at 45 and 35%, respectively. 16 Owing to the ease of the PAC in the ICU postoperatively, and the lack of availability of TEE in most ICUs, PAC remains the most commonly used modality. Major complica-tions associated with PAC have been reported to occur in 4 –5% of insertions. Intermittent transcuta-neous echo requires a lot of resources and is most likely only applicable in settings where

after LT and only a small percentage of patients will develop long -term kidney failure.

If necessary, renal replacement therapy should be initiated early, before fl uid overload or hyperkalemia are dominant after LT. In spite of this fact, there is little data available on the value of intraoperative RRT, although some centers fi nd it useful in managing the fl uid status intraoperatively.

Cardiovascular complications

Liver transplant centers perform risk stratifi cation for patients by evaluating their pre -transplant cardiac performance by using a dobutamine stress echocar-diogram or myocardium scintigraphy to detect critical coronary artery stenosis. If there are questions based on these screening tests, cardiologic consultation should be obtained. It has been acknowledged that non-alcoholic steatohepatitis (NASH), a history of previous coronary artery disease, and peripheral vascular disease in asymptomatic patients are strong risk predictors in patients with liver disease, as are hypertension, diabetes, hyperlipidemia, age >50, and obesity. 11 Programs with a higher percentage of patients with NASH should pursue a more aggressive screening strategy.

Specifi c attention should be paid to patients who have a positive stress test but a negative catheteriza-tion. It has been demonstrated that there are more postoperative deaths in patients with positive stress tests even if their catheterization was negative. 12

Patients with impaired cardiac performance may present in the ICU with myocardial depression and insuffi cient cardiac reserve, especially in the face of bleeding or sepsis. 13 At baseline, liver transplant patients have a high cardiac output state, low systemic vascular resistance, and a chronic infl ammatory condition. The procedure of LT constitutes severe physiologic stress with a wide range of changes in oxygen requirement by the myocardium. Plaque rupture and coronary thrombosis may occur in patients who have normal stress tests and subcritical stenoses ( <50% occlusions). Whether subcritical stenoses should be treated in preparation for LT or whether patients at high risk with negative stress tests should nevertheless undergo coronary catheterization are currently areas of debate. Reports have shown that myocardial infarction may occur in liver transplant recipients with as little as 30% of vessel occlusion. 12

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respiratory morbidity in liver transplant recipients with different grades of COPD. Reversible pulmonary pathologies like pleural effusions due to hepatic hydrothrorax, lobar collapse, and pneumothorax secondary to vascular access procedures or surgical injury to the diaphragm or phrenic injury as well as reduced ventilatory volume due to restriction from postoperative ascites may easily be identifi ed on chest x -ray. In the current authors ’ experience, reversible pathologies should be aggressively addressed with interventional procedures. Not resolving pleural effusions after LT, especially in conjunction with mild graft dysfunction, warrant thorough workup of right heart function and pulmonary arterial pressures.

Hepatopulmonary syndrome (HPS) is defi ned by the triad of liver dysfunction or portal hyperten-sion, abnormal gas exchange and evidence of pulmonary vascular shunts. The latter is diagnosed by echocardiography with the use of air bubbles or macroaggreated albumin perfusion scanning. Patients with HPS have an increased length of stay in ICU (median 4 d) and hospital (median of 39 d). The median time to cessation of oxygen is 4.5 months in some series. 21

Faenza et al. found that the PaO2/FiO2 ratio of <300 (an element of the defi nition of acute lung injury) at the end of a liver transplant predicts the need for prolonged mechanical ventilation in liver transplant patients. 22 There is no evidence that the mode of ventilation should be different in liver transplant patients compared to other post -surgicalpatients to improve graft outcomes. The current authors recommend that standard low -tidal ventila-tion is used to avoid ventilator -induced lung injury. Despite contrary reports in animal models, 23–25

there is no conclusive evidence that positive end expiratory pressure (PEEP) up to 15 cmH2 impairs liver outfl ow or systemic hemodynamics in liver transplant patients. 26 As long there is no dilatation of the right ventricle, PEEP does not infl uence hepatic outfl ow.

Patients cared for in the ICU prior to transplant are at risk for prolonged ventilation due to pre -existingventilation and concomitant loss of muscle mass. Patients intubated postoperatively for more than 5–7d should most likely undergo a tracheotomy. Waller at al. demonstrated that percutaneous dilata-tional tracheotomy with direct bronchoscopic

Echocardiograms are performed by physicians them-selves. Preliminary data suggest that this technique overestimates the cardiac output in subjects with low peripheral vascular resistance. 17 Many studies have demonstrated that central venous pressure measure-ment is a poor volume guide for intravascular volume and adequate resuscitation.

Oliguria should prompt TTE to improve cardiac fi lling with bolus colloids. If there is no fl uid respon-siveness to fl uid bolus, no more fl uids should be given to avoid over -resucitation based on central venous pressure (CVP), urinary output or pulmonary artery wedge pressure (PAWP) numbers.

Despite early reports that low -CVP resuscitation strategies result in more acute tubular necrosis (ATN) and decreased survival, more recent reports support the concept for restrictive fl uid and transfusion management.18,19 Whereas Massicotte et al. demon-strate that there is no need for albumin, fresh –frozenplasma (FFP) and platelet transfusion after LT, a problem of their study is the low mean MELD score of their patient population and the lack of a subgroup analysis with chronic renal disease. 18 Feng et al. confi rmed in a randomized prospective trial that low CVP during the pre -anhepatic phase results in about a 50% reduction in blood loss and transfusion requirements without any adverse effects on mortality or renal function. 19

Respiratory complications

There is good evidence that extubation of patients who have had cardiac surgery and major abdominal surgery reduces length of ICU and hospital care without a negative impact on morbidity and mortal-ity. A recent multicenter study confi rmed that fast-track management with extubation of liver trans-plant patients in the operating room can be achieved with only a 7.7% risk of adverse advents. 20 Non -invasive ventilation (NIV) is a possibility to avoid re-intubation if aspiration precautions are taken.

In order to assess the patient ’s ability to be extu-bated early, pre -existing lung pathologies need to be known. All patients undergoing LT should have screening spirometry. Structural lung disease might be an exclusion criterium for LT. Most programs do not transplant patients with severe chronic obstructive pulmonary disease (COPD) (FEV1 <50%).There is no study to date defi ning postoperative

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in post -LT patients compared to other post -surgicalpopulations. Patients with hyponatremia are at risk for central pontine myelinolysis and patients with fulminant hepatic failure have increased intracerebral pressures. Doppler ultrasound for the evaluation of elevated ICP might be helpful.

The early extubation group generally receives pain management with short -acting opiates like fentanyl based on pain level assessed by ICU nurses. Fast -trackpatients are cooperative in the operating room before they reach the ICU. Any change in their mental status should be carefully evaluated. A common reason for change in mental status in this patient population is the effect of starting calcineurin inhibitors. The current authors routinely employ a “calcineurinholiday” and use induction agents to bridge the time period of observation. If there are any neurologic focal defi cits or the patient suddenly becomes uncon-scious, a computed tomography (CT) of the head needs to be obtained to rule out a stroke. If mental changes go along with signs of systemic infections like fever and elevated white blood counts, systemic infection needs to be ruled by blood cultures. If central nervous system (CNS) infection is suspected as a source, contrast -enhanced magnetic resonance imaging (MRI) of the brain and then possibly spinal tap are indicated. If both sepsis and calcineurin inhib-itors are excluded as the source, frequent symptomatic treatment and expectant management is indicated. Treatment of delirium and combative states with benzodiazepines frequently results in a long setback of stupor and coma. Aggressive therapy with antipsychotic medications is much more effective. Haloperidol, risperidone, olanzepine and quetiapine are successfully used depending on the route of administration and at low starting doses. Risperidone and olanzapine are available in a quick -dissolvingtablet that may be given to ICU patients who have not yet been started on an oral regimen. Nevertheless, potential interactions must be considered. Later, after the transplant course, but sometimes during their ICU stay, patients might develop anxiety disorders and insomnia. There is again a temptation to treat this with benzodiazepines. If benzodiazepines are used, short-acting medications with no active metabolites (e.g. lorazepam) and the shortest possible course are recommended. The current authors have found, however, that most states of anxiety and insomnia are better treated with non -addicting agents like selective

guidance can safely be performed in liver transplant recipients, even in the face of coagulation abnormali-ties.27 Early tracheotomy provides the ability to reduce sedation, aggressively wean from mechanical ventilator support, improve patient comfort, enhance participation in physical therapy, and improve overall patient care.

Transient severe pulmonary edema might occur due to transfusion -related lung injury (TRALI). TRALI has been reported in LT and may occur due to trans-fusion of packed red blood cells, FFP or platelets. It has been linked to anti -neutrophile or anti -HLA anti-bodies contained in the transfusion volume. TRALI generally follows a transfusion incident and needs to be carefully differentiated from other causes of sudden de-oxygenation (pulmonary embolism, myocardial infarction, and acute respiratory distress syndrome (ARDS)). Sometimes temporary extra -corporal gas exchange may become necessary (extracorporal mem-brane oxygenation (ECMO)).

Neuropsychiatric complications

Neuropsychiatric complications occur in up to 30% of liver transplant patients and require extensive man-agement in the ICU. Chiu et al. reported that after LT the three equally most common reasons for psychiat-ric consultation were delirium, anxiety disorders, and depression.28

The liver transplant population contains a high percentage of patients with substance abuse problems involving nicotine, alcohol, IV drugs, marihuana, medications for chronic pain, benzodiazepines and sometimes long -term methadone use to treat depend-ency states. Patients might have a pre -existing history of seizure disorder, sometimes due to past cerebral hemorrhage due to falls. During their liver transplant work-up, patients are found to have varying degrees of hepatic encephalopathy and if accompanied by renal insuffi ciency, a component of uremic enceph-alopathy. Both tacrolimus and cyclosporine have neuropsychiatric side effects ranging from coma and cognitive impairment to seizures, delirium, and neu-ropathies.29,30 Susceptibility to calcineurin inhibitor (CNI) change during the transplant course might be related to changes in the blood –brain barrier permeability to circulating CNI due to improving liver function and the evolving ischemia reperfusion injury from the new graft. 28 The stroke risk is increased

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gastrointestinal bleeding. If the diagnosis is made during the ICU stay, the patient will generally be re-explored and thrombectomized.

Graft congestion due to outfl ow obstruction at the suprahepatic vena cava anastomosis results in initially delayed graft function and possibly bleeding from hepatic congestion. Doppler ultrasound might give a hint but defi nite diagnosis needs to be obtained by conventional cavography. Surgical correction has been described, but is not always possible and patients frequently take a subacute course until balloon dilata-tion can be performed after a few weeks. Stent placement will sometimes be necessary.

Biliary complications remain frequent after LT with varying incidence between 1.6 –18% for leaks and 3–23% for strictures. Multiple risk factors have been identifi ed for biliary complications including technical issues, graft ischemia, and immunologic factors. Early bile leaks should be suspected in any patients with constant abdominal pain after liver transplant or unclear fever. Most leaks occur from anastomosis and present early; many require surgical repair although endoscopic stenting may be success-ful. Late bile leaks (after 30 d) are rare, while late strictures are the most frequent cause of biliary complications after LT, often associated with recur-rent cholangitis. Treatment of anastomostic strictures usually requires endoscopic stenting; intrahepatic strictures are more complex and may lead to retransplantation.

Postoperative hypotension resulting from hypo-volemia, decreasing hematocrit and/or bleeding from operative drains requires immediate return to the operating room to control bleeding. In most patients who are returned to the operating room for bleeding, no defi nite source of bleeding can be detected. Bleeding in these cases may be associated with fi brinolysis and diffuse oozing from multiple raw surfaces, especially at the retrohepatic (bare) area. A rule of 6 U transfused in the immediate postopera-tive period mandates re -exploration for control of bleeding and removal of hematoma. Delay in re-exploration can lead to renal injury, increased risk of infection, and sometimes ischemia of the graft due to under resuscitation and overuse of vasoactive agents.

There are no evidence -based transfusion algorithms available and adaptation of trauma algorithms is not recommended. Resuscitation of bleeding

serotonin-uptake inhibitors (fl uoxetine, paroxetine, sertraline, and citalopram). Fluvoxamine and nafzo-done have signifi cant interactions with calcineurin inhibitors and should be avoided. Psychiatric consul-tation is strongly indicated in these patients.

The patient population arriving in the ICU intu-bated may be more challenging. Patients with pre-existing, albeit remote, dependency disorders are sometimes not cooperative enough to be extubated in the operating room. Generally normalization of intracerebral pressure is fast in patients with fulmi-nant failure and an eventual intracranial pressure (ICP) monitor should be discontinued within the fi rst 72h. If graft function is good but there is a history of hepatic encephalopathy or substance dependence, a combative, noncooperative patient who is diffi cult to extubate despite good pulmonary function is common. In patients with prolonged neurologic defi cit, neuro-logic consultation should be obtained, and status epilepticus ruled out by electroencephalogram (EEG). Even if there are no signs of systemic infections, fungal infections should be considered, especially in the debilitated patient population (those with severe prolonged liver disease, re -transplantation).

Surgical complications

Despite standardization and technical advances in LT, technical complications occur during the stay in the ICU. The most feared surgical complication is HAT. Today the incidence should be <2–3%, albeit higher in pediatric recipients. Of these patients, 30% develop signs of acute hepatic necrosis with high transami-nases, sepsis, mental status changes and coagulopathy, but some courses are more subacute with progressive biliary infections and hepatic dysfunction. Suspicion of HAT should trigger immediate Doppler ultrasound potentially confi rmed by an arteriogram. CT angi-ograms or MRIs have been shown to be appropriate substitutes for conventional angiography. In many organ procurement systems, HAT within the fi rst week after OLT is an absolute indication for the relisting of the recipient with urgent status.

Portal vein thrombosis in the ICU is also a rare vascular complication and is diagnosed by Doppler ultrasound. Graft failure due to portal vein thrombo-sis has been reported, but is infrequent and the majority of cases will present with manifestation of portal hypertension like massive ascites and possibly

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Prediction of risk

Survival models have been developed to help with patient and donor selection for LT but they may also serve as a surrogate to the intensive care specialist to estimate the morbidity of patients who are admitted after LT. Targeted management of risk arising from co -morbidities helps to decrease complications by addressing them early in the recipients’ postoperative course.

Importantly, the outcome of LT today is dominated by two recent developments: the introduction of the MELD score in many transplant systems worldwide and the aggressive allocation of grafts with extended criteria to expand the donor pool and decrease time to transplantation for recipients. Several attempts have therefore been undertaken to better predict post -transplant outcome before the transplantation procedure (Table 26.1). They include models either considering donor (donor risk index, DRI 1 or recipi-ent factors alone (survival after LT, Survival After Liver Transplantation (SALT) score), 33 or others that combine two dominant factors in donors and recipi-ents (donor age and recipient MELD, D -MELD)34 or even an extensive list of donor and recipient param-eters (survival outcome following LT, Survival Outcome Following liver Transplantation (SOFT)). 35

Both strategies have disadvantages, as for example the selection of only one donor and recipient factor (D-MELD) implies no possibility to balance high donor age in high MELD recipients. On the other side, inclusion of numerous covariates (SOFT score) results in wide extension of the score range.

Based on the large United Network for Organ Sharing (UNOS) database, an extended analysis of 37.255 patients between March 2002 and September 2010 identifi ed the six strongest predictors of post -transplant survival: 1) recipient MELD score, 2) cold ischemia time, 3) recipient age, 4) donor age, 5) previ-ous OLT, and 6) life support dependence prior to transplant. A new balance of risk (BAR) score was suggested, based on these parameters, to stratify recipients in terms of patient survival. The BAR system provides a simple and reliable tool to detect unfavorable combinations of donor and recipient factors, and is readily available prior to decision making of accepting or not an organ for a specifi c recipient. This score may offer great potential for better justice and utility, as it appears to be superior to other recently developed prediction scores. 36

coagulopathic patients is largely based on absolute numbers of cells, prothrombin time/internationalized normalized ratio (PT/INR), and fi brinogen levels. Thrombo-elastography (TEG) has successfully reduced transfusion requirements and blood loss in cardiac surgery and the algorithms tested in those patients have been used in other patient populations. Antifi brinolytic therapy with aminocaproic acid may be initiated based on evidence of hyperfi brinolysis on TEG.

Nutritional management

Half of the patients undergoing LT are found to be malnourished by subjective global nutritional assessments and the presence of malnutrition is an independent risk factor for the length of stay in the ICU. Oral feeding should start as soon as possible after LT. A protein -rich diet is recommended as the liver patient needs 1.5 –2g protein per kg body weight per day. If oral intake is not suffi cient, post -pyloric feeding through a tube should be instituted without delay. Glutamine -containing formulae have shown positive effects on outcome in critically ill patients and the current authors recommend their use in liver transplant recipients. Parenteral nutrition should be initiated if tube feeding is ineffective within 1 week.

Few centers routinely place a nasojejunal feeding tube to provide enteral feeding immediately postop-eratively while the patient has a gastric and colonic ileus. In a randomized study of enteric tube feeding vs control, Hasse et al. have convincingly demon-strated that tube -fed patients had a better nitrogen balance, less viral infections, and a trend towards fewer bacterial infections when undergoing tube feeding within 12 h after LT. 32

Peptic ulcer prophylaxis is important, especially in patients with gastro esophageal refl ux or pre -existingvariceal bleeding. Normally proton pump inhibitors (PPIs) are the fi rst choice. In a suffi ciently enterally fed patient, PPIs can be discontinued.

Due to the use of steroids tight glucose control may be challenging in liver transplant recipients. The current authors have applied the protocols of tight glucose control in ICU patients 31 to the liver trans-plant population and aim at keeping the plasma glucose levels between 5 and 9 mmol/L.

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Table 26.1 Currently available prediction models for survival (prediction of risk)

Name of risk model

End point Parameters entering into model Score range Score cut -off

MELD Recipient survival on waiting list at 3 months

bilirubinINRcreatinine

6 to >40

DRI Recipient survival Donor age Donor height Donation after cardiac death Split liver donors RaceDonor cause of death from cerebrovascular accident Cold ischemia time

1 to >2

SALT Recipient survival at 12 months

Recipient age Cholinesterase

D-MELD Overall survival RaceMELD

20 to >2000

SOFT Recipient survival at 3 months

Age, BMI, Retransplant, previous abdominal surgery, albumine, dialysis, ICU status,

Admitted to hospital, MELD, life support, encephalopathy, portal vein thrombosis, Ascites, portal bleed 48 hours prior, donor age, donor cause of death, donor creatinine, national allocation, CIT

0 to >40

BAR Recipient survival at 3 months

MELDRecipient age Donor age Previous OLT, Life support prior to transplant CIT

0–27

bedside test for maximal liver function capacity . AnnSurg 2009;250:119–25.

6. Stockmann M, Lock JF , Malinowski M, et al. How to defi ne initial poor graft function after liver transplanta-tion? – a new functional defi nition by the LiMAx test .Transpl Int 2010;23:1023–32.

7. Rayes N, Seehofer D, Theruvath T, et al. Supply of pre -and probiotics reduces bacterial infection rates after liver transplantation –a randomized, double -blind trial .Am J Transplant 2005;5:125–30.

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