Shawn J. Pelletier

Liver transplantation in the United States, 1999-2008.

Changes in organ allocation policy in 2002 reduced the number of adult patients on the liver transplant waiting list, changed the characteristics of transplant recipients and increased the number of patients receiving simultaneous liver–kidney transplantation (SLK). The number of liver transplants peaked in 2006 and declined marginally in 2007 and 2008. During this period, there was an increase in donor age, the Donor Risk Index, the number of candidates receiving MELD exception scores and the number of recipients with hepatocellular carcinoma. In contrast, there was a decrease in retransplantation rates, and the number of patients receiving grafts from either a living donor or from donation after cardiac death. The proportion of patients with severe obesity, diabetes and renal insufficiency increased during this period. Despite increases in donor and recipient risk factors, there was a trend towards better 1‐year graft and patient survival between 1998 and 2007. Of major concern, however, were considerable regional variations in waiting time and posttransplant survival. The current status of liver transplantation in the United States between 1999 and 2008 was analyzed using SRTR data. In addition to a general summary, we have included a more detailed analysis of liver transplantation for hepatitis C, retransplantation and SLK transplantation.

Impact of a rotating empiric antibiotic schedule on infectious mortality in an intensive care unit

Objective The development of antibiotic-resistant bacteria is associated with significant morbidity and mortality in critically ill patients. We postulated that quarterly rotation of empirical antibiotics could decrease infectious complications from resistant organisms in an intensive care unit (ICU). Design Prospective cohort study. Setting An ICU at a university medical center. Subjects All patients admitted to the general, transplant, or trauma surgery services who developed pneumonia, peritonitis, or sepsis of unknown origin. Interventions A 2-yr study consisting of 1 yr of nonprotocol-driven antibiotic use and 1 yr of rotating empirical antibiotic assignment. Measurements and Main Results Over 100 variables were recorded for each infectious episode, including patient characteristics (e.g., Acute Physiology and Chronic Health Evaluation [APACHE] II score, age, comorbidities), infection characteristics (e.g., site, organism), treatment characteristics (e.g., antibiotic, treatment duration) and outcome measures (e.g., mortality, length of stay, antibiotic cost). Of 1456 consecutive admissions to the ICU, 540 episodes of infection were treated. No differences were noted in age, APACHE II score, race, overall antibiotic utilization or duration of therapy between the 2 yrs of study. Outcome analysis revealed significant reductions in the incidence of antibiotic-resistant Gram-positive coccal infections (7.8 infections/100 admissions vs. 14.6 infections/100 admissions, p < .0001), antibiotic-resistant Gram-negative bacillary infections (2.5 infections/100 admissions vs. 7.7 infections/100 admissions, p < .0001), and mortality associated with infection (2.9 deaths/100 admissions vs. 9.6 deaths/100 admissions, p < .0001) during rotation. Logistic regression identified age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01–1.06), APACHE II score (OR, 1.06; 95% CI, 1.01–1.13), solid organ transplantation (OR, 9.50; 95% CI, 2.01–52.21), and malignancy (OR, 10.16; 95% CI, 4.11–26.96) as independent predictors of mortality. Antibiotic rotation was an independent predictor of survival (OR 6.27, 95% CI 2.78–14.16). Conclusion Rotation of empirical antibiotic therapy seems to be a promising method to reduce infectious mortality in an ICU.

Donation after cardiac death as a strategy to increase deceased donor liver availability.

Objective:This study examines donation after cardiac death (DCD) practices and outcomes in liver transplantation. Summary Background Data:Livers procured from DCD donors have recently been used to increase the number of deceased donors and bridge the gap between limited organ supply and the pool of waiting list candidates. Comprehensive evaluation of this practice and its outcomes has not been previously reported. Methods:A national cohort of all DCD and donation after brain-death (DBD) liver transplants between January 1, 2000 and December 31, 2004 was identified in the Scientific Registry of Transplant Recipients. Time to graft failure (including death) was modeled by Cox regression, adjusted for relevant donor and recipient characteristics. Results:DCD livers were used for 472 (2%) of 24,070 transplants. Annual DCD liver activity increased from 39 in 2000 to 176 in 2004. The adjusted relative risk of DCD graft failure was 85% higher than for DBD grafts (relative risk, 1.85; 95% confidence interval, 1.51–2.26; P < 0.001), corresponding to 3-month, 1-year, and 3-year graft survival rates of 83.0%, 70.1%, and 60.5%, respectively (vs. 89.2%, 83.0%, and 75.0% for DBD recipients). There was no significant association between transplant program DCD liver transplant volume and graft outcome. Conclusions:The annual number of DCD livers used for transplant has increased rapidly. However, DCD livers are associated with a significantly increased risk of graft failure unrelated to modifiable donor or recipient factors. Appropriate recipients for DCD livers have not been fully characterized and recipient informed consent should be obtained before use of these organs.

Persistent occult hypoperfusion is associated with a significant increase in infection rate and mortality in major trauma patients.

OBJECTIVE To investigate the hypothesis that occult hypoperfusion (OH) is associated with infectious episodes in major trauma patients. METHODS Data were collected prospectively on all adult trauma patients admitted to the Surgical/Trauma Intensive Care Unit from November of 1996 to December of 1998. Treatment was managed by a single physician according to a defined resuscitation protocol directed at correcting OH (lactic acid [LA] > 2.4 mmol/L). RESULTS Of a total of 381 consecutive patients, 118 never developed OH and 263 patients exhibited OH. Seventeen patients were excluded because their LA never corrected, and they all subsequently died. One hundred seventy-six infectious episodes occurred in 97 of the 364 patients remaining. The infection rate in patients with no elevation of LA was 13.6% (n = 118) compared with 12.7% (n = 110) in patients whose LA corrected by 12 hours, 40.5% (n = 79; p < 0.01 compared with all other groups) in patients whose LA corrected between 12 and 24 hours, and 65.9% (n = 57; p < 0.01 compared with all other groups) in patients who corrected after 24 hours. Among the patients with infections, there were 276 infection sites with 42% of infections involving the lung and 21% involving bacteremia. There was no difference in proportion of infections occurring at each site between groups. The mortality rate of patients who developed infections was 7.9% versus 1.9% in patients without infections (p < 0.05). Of the patients who developed infections, 69.8% versus 25.8% (p < 0.001) did not have their lactate levels normalized within 12 hours of emergency room admission. Logistic regression demonstrated that both the Injury Severity Score and OH > 12 hours were independently predictive of infection. CONCLUSION A clear increase in infections occurred in patients with OH whose lactate levels did not correct by 12 hours, with an associated increase in length of stay, days in surgical/trauma intensive care unit, hospital charges, and mortality.

UNI- AND MULTI-VARIATE ANALYSIS OF RISK FACTORS FOR EARLY AND LATE HEPATIC ARTERY THROMBOSIS AFTER LIVER TRANSPLANTATION

Background. Hepatic artery thrombosis (HAT) is a significant cause of morbidity after liver transplantation. The aims of this study are to identify and compare risk factors that might contribute to HAT. Methods. A total of 424 liver transplants performed at the University of Virginia were reviewed. HAT was defined as complete disruption of arterial blood flow to the allograft and was identified in 29 cases (6.8%). HAT was classified as early (less than 1 month posttransplant, 9 cases: 2.1%) or late (more than 1 month posttransplant, 20 cases: 5.4%). Possible risk factors for HAT were analyzed using Pearson &khgr;2 test for univariate analysis and logistic regression for multivariate analysis. Results. Multiple transplants, recipient/donor weight ratio >1.25, biopsy-proven rejection within 1 week of transplant, recipient negative cytomegalovirus (CMV) status, arterial anastomosis to an old conduit (defined as a previously constructed aorto-hepatic artery remnant using donor iliac artery), and CMV negative patients receiving allograft from CMV positive donors were found to be significant risk factors for developing early HAT. After logistic regression, factors independently predicting early HAT included arterial anastomosis to an old conduit [odds ratio (OR)=7.33], recipient/donor weight ratio >1.25 (OR=5.65), biopsy-proven rejection within 1 week posttransplant (OR=2.81), and donor positive and recipient negative CMV status (OR=2.66). Female donor, the combination of female donor and male recipient, recipient hepatitis C-related liver disease, donor negative CMV status, and the combination of recipient CMV negative and donor CMV negative were found to be significant risk factors for late HAT. Factors independently predicting late HAT by logistic regression included negative recipient and donor CMV status (OR=2.26) and the combination of a female donor and male recipient (OR=1.97). Conclusion. Therefore, in nonemergency situations attention to these factors in donor allocation may minimize the possibility of HAT.

Seasonal variation in surgical outcomes as measured by the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP).

Objective:We hypothesize that the systems of care within academic medical centers are sufficiently disrupted with the beginning of a new academic year to affect patient outcomes. Methods:This observational multiinstitutional cohort study was conducted by analysis of the National Surgical Quality Improvement Program–Patient Safety in Surgery Study database. The 30-day morbidity and mortality rates were compared between 2 periods of care: (early group: July 1 to August 30) and late group (April 15 to June 15). Patient baseline characteristics were first compared between the early and late periods. A prediction model was then constructed, via stepwise logistic regression model with a significance level for entry and a significance level for selection of 0.05. Results:There was 18% higher risk of postoperative morbidity in the early (n = 9941) versus the late group (n = 10313) (OR 1.18, 95%, CI 1.07–1.29, P = 0.0005, c-index 0.794). There was a 41% higher risk for mortality in the early group compared with the late group (OR 1.41, CI 1.11-1.80, P = 0.005, c-index 0.938). No significant trends in patient risk over time were noted. Conclusion:Our data suggests higher rates of postsurgical morbidity and mortality related to the time of the year. Further study is needed to fully describe the etiologies of the seasonal variation in outcomes.

Portal Vein Thrombosis and Survival in Patients with Cirrhosis

The effects of occlusive portal vein thrombosis (PVT) on the survival of patients with cirrhosis are unknown. This was a retrospective cohort study at a single center. The main exposure variable was the presence of occlusive PVT. The primary outcome measure was time‐dependent mortality. A total of 3295 patients were analyzed, and 148 (4.5%) had PVT. Variables independently predictive of mortality from the time of liver transplant evaluation included age [hazard ratio (HR), 1.02; 95% confidence interval (CI), 1.01‐1.03], Model for End‐Stage Liver Disease (MELD) score (HR, 1.10; 95% CI, 1.08‐1.11), hepatitis C (HR, 1.44; 95% CI, 1.24‐1.68), and PVT (HR, 2.61; 95% CI, 1.97‐3.51). Variables independently associated with the risk of mortality from the time of liver transplant listing included age (HR, 1.02; 95% CI, 1.01‐1.03), transplantation (HR, 0.65; 95% CI, 0.50‐0.81), MELD (HR, 1.08; 95% CI, 1.06‐1.10), hepatitis C (HR, 1.50; 95% CI, 1.18‐1.90), and PVT (1.99; 95% CI, 1.25‐3.16). The presence of occlusive PVT at the time of liver transplantation was associated with an increased risk of death at 30 days (odds ratio, 7.39; 95% CI, 2.39‐22.83). In conclusion, patients with cirrhosis complicated by PVT have an increased risk of death. Liver Transpl 16:83–90, 2010.

An intention-to-treat analysis of liver transplantation for hepatocellular carcinoma using organ procurement transplant network data

Single‐center studies have shown acceptable long‐term outcomes following orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) when tumors are within the Milan criteria. However, the overall survival and waiting list removal rates have not been described at a national level with pooled registry data. To evaluate this, a retrospective cohort of patients listed for OLT with a diagnosis of HCC between January 1998 and March 2006 was identified from Organ Procurement Transplant Network data. Analysis was performed from the time of listing. Adjusted Cox models were used to assess the relative effect of potential confounders on removal from the waiting list as well as survival from the time of wait listing. A total of 4482 patients with HCC were placed on the liver waiting list during the study period. Of these, 65% underwent transplantation, and 18% were removed from the list because of tumor progression or death. The overall 1‐ and 5‐year intent‐to‐treat survival for all patients listed was 81% and 51%, respectively. The 1‐ and 5‐year survival was 89% and 61% for those listed with tumors meeting the Milan criteria versus 70% and 32% for those exceeding the Milan criteria (P < 0.0001). On multivariate analysis, advanced liver failure manifested by Child‐Pugh class B or C increased the risk of death, while age < 55 years, meeting the Milan criteria, and obtaining a liver transplant were associated with better survival. The current criteria for liver transplantation of candidates with HCC lead to acceptable 5‐year survival while limiting the dropout rate. Liver Transpl 15:859–868, 2009.

Increased early morbidity and mortality with acceptable long‐term function in severely obese patients undergoing liver transplantation

The effect of obesity on outcomes following liver transplantation remains unclear. We reviewed our experience with 302 liver transplants in 277 patients from September 1989 to September 1996 to determine the effect of body mass on outcome. Two hundred and seventeen transplants were performed in patients with a body mass index (BMI)<30 kg/m2, 55 in patients with a BMI of 30–34 kg/m2 (obese), and 30 in patients with a BMI>35 kg/m2 (severely obese). Non‐weight related pre‐operative demographics were similar between groups with the exception of an increased frequency of cryptogenic cirrhosis among the obese and severely obese patients. Intra‐operative transfusion requirements were greater for the severely obese group (16.2±3.5 units versus 9.1±0.8 units for the non‐obese, p=0.0004), though not when normalized to body weight (0.14±0.03 units/kg versus 0.13±0.01 units/kg, p>0.05). Post‐operatively, severely obese patients had a higher rate of wound infection (20 versus 4%, p=0.0001) and death attributed to multisystem organ failure (15 versus 2%, p=0.0001), although overall mortality prior to discharge and total complications were not different between groups. Actual 1‐yr graft survival showed a negative trend in the severely obese group (67 versus 81% for non‐obese, p=0.07), but both 3‐yr graft survival and patient survival were similar to non‐obese patients (p=0.12 and 0.17, respectively by the Cox–Mantel test). Liver transplantation in severely obese patients is associated with wound infection and early death from multisystem organ failure, but has similar long‐term outcomes when compared to non‐obese controls.

Impact of antibiotic-resistant Gram-negative bacilli infections on outcome in hospitalized patients.

ObjectiveThe impact of resistant (vs. nonresistant) Gram-negative infections on mortality remains unclear. We sought to define risk factors for and excess mortality from these infections. DesignProspective cohort study. SettingInpatient surgical wards at a university hospital. PatientsAll patients in the general, transplant, and trauma surgery services diagnosed with Gram-negative rod (GNR) infection. Measurements and Main ResultsAll culture-proven GNR infections (n = 924) from December 1996 to September 2000 were studied. Characteristics and outcomes were compared between GNR infections with and without antibiotic resistance. Univariate and logistic regression analysis identified factors associated with antibiotic-resistant GNR (rGNR) infection and mortality. rGNR infection (n = 203) was associated with increased Acute Physiology and Chronic Health Evaluation (APACHE) II scores (17.8 ± 0.5), multiple comorbidities, pneumonia and catheter infection, coexistent infection with antibiotic-resistant Gram-positive cocci and fungi, and high mortality (27.1%). Only seven isolates were resistant in vitro to all available antibiotics. Logistic regression demonstrated that rGNR infection was an independent predictor of mortality (odds ratio, 2.23; 95% confidence interval, 1.35–3.67;p = .002). Analysis of rGNR infection with controls matched by organism, age, APACHE II score, and site of infection, however, revealed that antibiotic resistance was not associated with increased mortality (23.6% vs. 29.2%, p = .35). Furthermore, analysis of all Pseudomonas aeruginosa infections demonstrated no significant difference in mortality between resistant and sensitive strains (18.9% vs. 20.0%, p = .85). ConclusionrGNRs are associated with prolonged hospital stay and increased mortality. Infection with rGNRs independently predicts mortality; however, this may be more closely related to selection of certain bacterial species with a high frequency of resistance rather than actual resistance to antibiotic therapy. Therefore, altering infection-control practices to limit the dissemination of certain bacterial species may be more effective than attempts to control only antibiotic-resistant isolates.