Risk factors for venous thromboembolism in patients with chronic liver disease.

BACKGROUND: Pharmacologic prophylaxis for venous thromboembolism (VTE) in patients with chronic liver disease (CLD) presents a unique challenge because of coagulopathies associated with the disease. When evaluating whether these patients require VTE prophylaxis upon hospitalization, it would be advantageous if risk factors for the development of VTE in this population were known. OBJECTIVE: To evaluate risk factors associated with the development of VTE in patients with CLD. METHODS: A retrospective case-control study was conducted. Patients admitted to the University of Kentucky Chandler Hospital from October 2006 to July 2010 with a diagnosis of CLD and VTE were matched in a 1:3 fashion with CLD patients without VTE. The primary objective was to determine whether there were significant differences in laboratory values between the 2 groups. RESULTS: During this time, 27 patients with CLD (1.0%) were diagnosed with VTE. These patients had significantly lower median aspartate aminotransferase (AST) (47 vs 70 U/L, p = 0.04), alanine transaminase (ALT) (24.5 vs 36 U/L, p = 0.02), albumin (2.1 vs 2.4 g/dL, p = 0.02) and hematocrit (Hct) (28.3% vs 32%, p = 0.03) values compared to the control patients. Patients with albumin lower than 1.9 g/dL had a 5.1 times greater risk of VTE compared to patients with albumin of 2.8 g/dL and higher (OR 5.14, 95% CI 1.05-25.2). CONCLUSIONS: Patients with CLD who developed VTE had significantly lower AST, ALT, albumin, and Hct compared to those of control patients. Studies are necessary to further examine the significance of this finding.

Pharmacotherapy of lung transplantation: an overview.

Lung transplantation has become a viable treatment therapy for end-stage lung disease patients. The most common etiologies of end-stage lung disease, which can require a transplant are chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), and pulmonary fibrosis (PF). Listing criteria are institution and program specific. Approximately 1500 lung transplants were performed in 2008; and at 5 years post transplant, one-half are expected to survive. The surgery itself is associated with various complications, including surgical, infectious, and mechanical. Immunosuppression is paramount to the management of these patients, the goal being prevention of T cell activation to prevent rejection of the new organ. The patients commonly receive an induction agent with a T cell depleting antibody and high-dose corticosteroids. Maintenance immunosuppression begins immediately after the surgery, consisting of a combination of a calcineurin inhibitor, antimetabolite, and corticosteroids. Side effect profiles from the various agents will determine the choice of agents, and patients may have modifications throughout the therapy. The role of the pharmacist spans the inpatient management of acute complications to medication selection, management of maintenance immunosuppression, as well as monitoring for adverse drug reactions and drug-drug interactions. A multidisciplinary collaborative approach must be taken to ensure the best outcomes for this patient population.

Effects of hyperglycemia on the development of new-onset diabetes after liver transplantation.

CONTEXT: New-onset diabetes after transplantation (NODAT) has been associated with cardiovascular and thrombotic complications, acute rejection, and infection in transplant recipients. NODAT in kidney transplantation is well described; however, data are lacking in liver transplant recipients. OBJECTIVE: To evaluate the incidence of new-onset diabetes within 6 months postoperatively in adult liver transplant recipients. DESIGN, PARTICIPANTS, SETTING, AND INTERVENTIONS: Patients who underwent a liver transplantation at our institution between January 2004 and December 2005 were retrospectively evaluated. NODAT was defined according to the diagnostic criteria of the American Diabetes Association/World Health Organization, persistent hyperglycemia (serum glucose > or = 200 mg/dL occurring 2 weeks after initial steroid induction and persisting for more than 2 weeks), or the need for hypoglycemic agents upon discharge. MAIN OUTCOMES: Incidence of NODAT within 6 months after transplantation in patients with poor glycemic control within the first 2 weeks after transplantation, acute rejection episodes, infections, hospital readmissions, and cardiovascular and thrombotic events. RESULTS: Forty-five patients were evaluated. Within the first 6 months after transplantation, NODAT developed in 11 (24%). Acute rejection, infection, hospital readmissions, cardiovascular events, and thrombotic events did not differ between the groups. CONCLUSION: Elevated fasting levels of blood glucose during the first 2 weeks after liver transplantation may be associated with an increased incidence of NODAT and may have predictive value. More studies are needed to determine the effects of recognition and treatment of hyperglycemia in recent transplant recipients.

Predictors of relapse to alcohol and illicit drugs after liver transplantation for alcoholic liver disease.

BACKGROUND: Alcoholic liver disease (ALD) is a common indication for transplantation worldwide. This study identifies factors predicting posttransplant recidivism. METHODS: Clinical and laboratory data were reviewed. Uni- and multivariate analyses for survival and relapse to alcohol and illicit drugs were performed. RESULT: Between July 1995 and November 2007, 387 patients underwent liver transplantation at our institution. Of these, 147 patients (38%) were found to have ALD. Five patients (3.4%) were excluded because of perioperative mortality. Overall survival was 96.2%, 89.6%, and 84.4% at 1, 3, and 5 years, respectively, with a median follow-up of 41.2 months. Twenty-seven patients (19%) returned to alcohol after transplantation. By univariate analysis, depression was the only significant factor affecting survival (P=0.01), whereas posttransplant relapse to alcohol trended toward significance (P=0.059). Multivariate analysis showed both factors to be independently associated with poor survival (P=0.008 and 0.017, respectively). Factors associated with relapse included less than 12 months of abstinence before transplant (P=0.019) and participation in rehabilitation (P=0.026). Multivariate analysis showed pretransplant abstinence less than 12 months as the only independent factor (P=0.037) associated with alcohol relapse after transplantation. Twenty-five patients (17.2%) had documented drug use after transplantation. Drug abuse before transplantation was the only independent predictor of drug abuse after transplantation (P=0.017). CONCLUSIONS: Excellent results can be obtained in patients undergoing liver transplantation for ALD, though depression and recidivism adversely impact survival. In our series, abstinence less than 12 months was associated with relapse to alcohol. Similarly, those with prior drug abuse are more likely to continue drug use after transplantation.

Seatbelt injury resulting in functional loss of a transplanted kidney.

The transplanted kidney, lying heterotopically in the iliac fossa, is especially vulnerable to damage from blunt trauma, particularly compression by vehicle seatbelt. We present a case wherein a functioning renal allograft lying in the right iliac fossa was severely injured by seatbelt compression, resulting in significant functional compromise and eventual loss. The patient later underwent successful retransplantation with a second living donor kidney. Management of injured renal transplant recipients requires appreciation of mechanisms likely to cause damage to the graft, as well as familiarity with available treatment options, both surgical and nonsurgical. As functional life spans of renal allografts improve, this type of injury will most likely be encountered with increasing frequency.

Prevalent immunosuppressive strategies in liver transplantation for hepatitis C: results of a multi-center international survey.

To determine current immunosuppression regimens and strategies for acute cellular rejection in hepatitis C virus (HCV) patients after liver transplantation (LT), questionnaires were sent to 264 LT programs worldwide. Surveys from 81 programs were reviewed. In 27 centers (33.8%) the immunosuppression protocol used in HCV differed from non-HCV patients. Tacrolimus-based immunosuppression is utilized in 70 centers (86.42%). Triple therapy using tacrolimus, mycophenolate mofetil and steroids is the most common regimen (41%). Six programs (7.4%) use steroid-free protocols. In nine centers (11%) steroids are discontinued within a week, 56% within 3 months, and 98% within the first year. At 75% of centers, mild rejection is treated by increasing baseline immunosuppression. Moderate rejection is treated by increasing baseline immunosuppression in 38% of centers, steroid bolus in 44%, and either in 16%. For severe rejection, 46% of centers give bolus steroid, and 16% administer antibodies. Among respondents, non-US programs use significantly more cyclosporine than US programs (35.6% vs. 2.8%, P<0.001). Duration of steroid therapy is significantly shorter in US programs than non-US (10.8 vs. 29.4 weeks, P<0.001). There is no consensus regarding the best immunosuppressive regimen and rejection treatments in HCV patients after LT. Our results reveal the most prevalent management practices in this difficult group of patients.

Pharmacy resident participation in cardiopulmonary resuscitation events.

PURPOSE: An electronically administered cross-sectional survey was conducted to establish the rate of pharmacy resident participation in cardiopulmonary resuscitation (CPR) events at pharmacy residency programs throughout the United States and Puerto Rico. METHODS: A 46-item questionnaire was developed and sent by e-mail to pharmacy residency program directors. The recipients were given one month to complete the survey. Responses were screened for duplicate answers, and the most complete survey was included in the analysis. The survey dealt with residency program demographics and sought information about required life-support certifications for pharmacy personnel, institution-specific training methods for medical emergencies employed by pharmacy departments, responsibilities of pharmacy personnel who respond to CPR events, and evaluation methods used to assess resident performance in CPR events. RESULTS: A total of 745 pharmacy residency directors were surveyed. Responses were received from 190 residency program directors, which represented 221 residency programs. The three most common residency program settings were community (not-for- profit) hospitals, college and university hospitals, and government hospitals. Thirty percent of respondents required pharmacy resident response to CPR events, while 38% made this opportunity optional. In 85% of programs that required or offered resident response to CPR events, there was a formal CPR team. The three primary roles fulfilled by pharmacists in medical emergencies were provision of drug information, drug admixture, and documentation; pharmacy resident duties mirrored these roles. CONCLUSION: Pharmacy resident response to CPR events was required in approximately 30% of responding pharmacy residency programs. Various methods were used in educating, assessing, and evaluating pharmacy residents in this role.

A pharmacoeconomic analysis of liver transplant charges.

OBJECTIVE: To analyze hospital charges for all liver transplant admissions to determine major cost drivers of the total charge. STUDY DESIGN: Retrospective review of hospital billing records. METHODS: Hospital charges were collected for all liver transplant admissions between July 1995 and December 2005 and 276 billing records were included in the analysis. Charges were itemized into pharmacy, inpatient room, laboratory, organ acquisition, and other. RESULTS: Despite maintaining a median length of stay of about 10 days, hospital charges increased from 1995 to 2005. Mean total pharmacy charges (+/- SEM) before a 1998 cost-containment initiative were $17,405 +/- $4,080 and constituted a 12% fraction of total charges, but had reduced to $11,238 +/- $2,828 (7.8% of total charges) immediately thereafter, decreasing to $9,891 +/- $2,351 (3.7% of total charges) for the most current period (2005). The increase in the total charge was largely driven by an increase in the organ acquisition charge and daily laboratory and room charges. CONCLUSIONS: Pharmacy charges no longer are a major contributor to the total liver transplant charges at our institution. A major reduction in total liver transplant charge can now only be achieved by targeting other cost centers such as laboratory, room, and organ acquisition. The transplant team has limited control over these cost centers.

Analysis of morbidity in liver transplant recipients following human albumin supplementation: a retrospective pilot study.

OBJECTIVES: To assess incidence of morbidity (i.e., documented infection, acute renal failure, acute graft rejection, acute cardiovascular events, and hospital readmission rates) 6 months following liver transplantation using linear regression as a function of cumulative albumin dose. DESIGN: Retrospective chart review. SETTING: A 473-bed tertiary care teaching facility with a solid-organ transplantation center. PATIENTS: Forty liver transplant recipients examined from January 1 to December 31, 2003. MEASUREMENTS AND RESULTS: Data from 40 liver transplant recipients were collected. Mean albumin dose administered was 190.9 +/- 162.3 g. No statistical differences were identified in patients receiving less than 140 g (n=20) or more than 140 g (n=20) with respect to demographic data other than gender and ethnicity. The mean APACHE III (Acute Physiology and Chronic Health) score was 69.7 +/- 24.3. Approximately 70 episodes of morbidity and 23 readmissions were observed. Regardless of the APACHE III score, albumin was associated with increased overall morbidity and cardiovascular complications. Liver transplant recipients receiving more than 140 g had a longer hospital stay (14 vs. 8 days, P = .025) and intensive care unit stay (6 vs. 3 days, P = .051) than patients receiving 140 g or less. No correlation with risk of acute rejection was seen with albumin or tacrolimus. Conclusion-Albumin supplementation among liver transplant recipients was associated with a significant risk for cardiovascular complications and overall number of complications regardless of APACHE III score. Future prospective studies are needed to further define the potential risk for complications in this patient population.

Enteral nutrition and drug administration, interactions, and complications.

The enteral route has become the standard of care to deliver nutrition support for hospitalized acute care and ambulatory care patients. The same access device is increasingly being used to deliver medications, which provides cost savings but also creates new challenges. Cost savings can be negated if the concomitant administration of nutrition elicits a decrease in bioavailability due to incompatibilities that alter drug or nutrition therapy. Feeding tubes can deliver nutrients and drugs to the stomach, small bowel, or both, with optimal efficacy of medications depending on delivery to the appropriate segment of the gastrointestinal tract. Liquid preparations are often the preferred formulation for enteral administration. Obstruction of the enteral access device may occur when specialized medication formulations are altered inappropriately. Occasionally, the enteral formula should be changed to modify the content of free water, fiber, electrolytes, or vitamins that may interfere with the drug therapy. Intolerance to enteral nutrition such as abdominal distention and diarrhea may be the result of the medication, and the causative agent should be identified to improve patient comfort. This article will address optimal drug delivery via enteral access devices and possible complications associated with therapy.

Celecoxib-induced nephrotoxicity in a renal transplant recipient.

A 47-year-old renal transplant recipient came to the transplant clinic with a serum creatinine level that was elevated above her baseline value. She had been taking celecoxib for arthritic pain. She was told to discontinue the drug, and shortly after, her serum creatinine level returned to baseline. Several case reports describe nephrotoxicity with cyclooxygenase (COX)-2 inhibitors. However, only two of these reports involved renal transplant recipients, and in both, rofecoxib was the COX-2 inhibitor of concern. To our knowledge, this is the first case report of a renal transplant recipient who developed nephrotoxicity while taking celecoxib. The potential renal effects of COX-2 inhibitors have received little attention, even though nonsteroidal anti-inflammatory drugs are considered to carry the risk of nephrotoxicity in patients with comorbidities such as diabetes mellitus and hypertension. Further studies are necessary to determine the safety of COX-2 inhibitors in transplant recipients and other patient groups that may be at heightened risk of nephrotoxicity.