Gianni Biancofiore

Evaluation of a new software version of the FloTrac/Vigileo (version 3.02) and a comparison with previous data in cirrhotic patients undergoing liver transplant surgery.

BACKGROUND: Reliable cardiac output monitoring is particularly useful in the cirrhotic patient undergoing liver transplant surgery, because cirrhosis of the liver is associated with a vasodilated and high output state, known as cirrhotic cardiomyopathy, that challenges the reliability of pulse contour cardiac output technology. The contractility of the ventricle in cirrhosis is impaired, which is tolerated even though the ejection fraction and cardiac output are elevated because of the low peripheral resistance. However, during surgery the cirrhotic patient can decompensate because of the physiological changes and stress of surgery. Recently, we showed that the FloTrac/Vigileo™ failed to perform in cirrhotic patients undergoing transplant surgery. In response, the company upgraded their software. Therefore, we have assessed the accuracy and reliability of this new third-generation (version 3.02) FloTrac/Vigileo algorithm software in the same setting. METHODS: The cardiac index was measured simultaneously by single-bolus thermodilution (CITD), using a pulmonary artery catheter, and pulse contour analysis, using the FloTrac/Vigileo (CIV). Readings were made at 10 time points during and after liver transplant surgery in 21 patients. Comparisons with data from our 2009 study, which used second-generation (version 01.10) software, were also made. RESULTS: Our new data show that version 3.02 software significantly reduced the adverse effect on pulse contour cardiac output reading bias in low peripheral resistance states, and thus improves the overall precision and trending ability of the system. Regression analysis between CITD and CIV showed that the correlation was moderate (r =0.67, 95% confidence interval, 0.40 to 0.86). The Bland and Altman analysis showed that bias was 0.4 L.min−1 · m−2, and the percentage error was 52% (95% confidence interval, 49% to 55%). Trending ability of the new software also was improved but was still well below the current benchmarks. CONCLUSION: The new software (version 3.02) provided substantial improvements over the previous versions with better overall precision and trending ability. Further algorithm refinements will increase this technology’s reliability to be extensively used in the highly complex setting of cirrhotic patients undergoing liver transplantation.

A multicenter evaluation of safety of early extubation in liver transplant recipients

Small single‐institutional studies performed prior to the introduction of organ allocation using the Model for End‐Stage Liver Disease (MELD) suggest that early airway extubation of liver transplant recipients is a safe practice. We designed a multicenter study to examine adverse events associated with early extubation in patients selected for liver transplantation using MELD score. A total of 7 institutions extubated all patients meeting study criteria and reported adverse events that occurred within 72 hours following surgery. Adverse events were uncommon: occurring in only 7.7% of 391 patients studied. Most adverse events were pulmonary or surgically related. Pulmonary complications were usually minor, requiring only an increase in ambient oxygen concentration. The majority of surgical adverse events required additional surgery. Analysis of a limited set of perioperative variables suggest that blood transfusions and technical factors were associated with an increased risk of adverse events. In conclusion, while early extubation appears to be safe under specified circumstances, there are performance differences between institutions that remain to be explained. Liver Transpl 13:1557–1563, 2007.

Cystatin C as a marker of renal function immediately after liver transplantation

To verify whether cystatin C may be of some use as a renal function marker immediately after orthotopic liver transplantation (OLT), we compared serum cystatin C (SCyst), serum creatinine (Scr), and creatinine clearance (Ccr) levels with the glomerular filtration rate (GFR). On postoperative days 1, 3, 5, and 7, SCyst and Scr was measured in simultaneously drawn blood samples, whereas Ccr was calculated using a complete 24‐hour urine collection. The GFR was determined on the same days by means of iohexol plasma clearance (I‐GFR). The correlation between 1/SCyst and I‐GFR was stronger than that of 1/Scr or Ccr (P< 0.01). In the case of moderate reductions in I‐GFR (80‐60 mL/minute/1.73 m), Scr remained within the normal range, whereas the increase in Scyst was beyond its upper limit; for I‐GFR reductions to lower levels (59‐40 mL/minute/1.73 m), Scr increased slightly, whereas Scyst was twice its upper normal limit. When we isolated all of the I‐GFR values on days 3, 5, and 7 that were ≥30% lower than that recorded on the first postoperative day, SCyst(P< 0.0001) and Scr (P< 0.01) levels were increased, whereas Ccr remained unchanged (P= 0.09). Receiver operating characteristic (ROC) area‐under‐the‐curve analysis showed that the diagnostic accuracy of Scyst was better than that of Scr and Ccr. Scyst levels of 1.4, 1.7, and 2.2 mg/L respectively predicted I‐GFR levels of 80, 60, and 40 mL/minute/1.73 m. In conclusion, cystatin C is a reliable marker of renal function during the immediate post‐OLT period, especially when the goal is to identify moderate changes in GFR. Liver Transpl 12:285–291, 2006.

Antifungal prophylaxis in liver transplant recipients: a randomized placebo‐controlled study

Abstract The aim of this study was to evaluate the efficacy of two antifungal prophylaxis regimens in liver transplant recipients. One hundred and twenty‐nine consecutive recipients were randomized to receive sequential treatment with intravenous liposomal amphotericin B + oral itraconazole, intravenous fluconazole + oral itraconazole, or intravenous and oral placebo. Frequency and incidence of mycotic colonization, local and systemic infection of mycotic origin, causes of death, and possible risk factors for mycotic infection were evaluated. The incidence of mycotic colonization was higher in the placebo group (P<0.01), but there was no significant difference in the incidence of infection between the three groups. Pre‐transplant colonization, severity of liver disease, and graft rejection were all risk factors for the development of fungal infection. The routine use of antifungal prophylaxis for all liver transplant recipients does not seem to be justified.

THE ROLE OF IMMUNOMODULATION IN ABO-INCOMPATIBLE ADULT LIVER TRANSPLANT RECIPIENTS

ABO‐incompatible (ABO‐i) liver transplantation (LT) is a high‐risk procedure due to the potential for antibody‐mediated rejection (AMR) and cell‐mediated rejection. The aim of the current report is to illustrate the results of a retrospective comparison study on the use of immunomodulation with therapeutic plasma exchange (TPE) associated to high‐dose immunoglobulins (IVIg) and extracorporeal photopheresis (ECP) in ABO‐i adult LT patients.

Use of Octogenarian Donors for Liver Transplantation: A Survival Analysis

Use of very old donors in liver transplantation (LT) is controversial because advanced donor age is associated with a higher risk for graft dysfunction and worse long‐term results, especially for hepatitis C virus (HCV)‐positive recipients. This was a retrospective, single‐center review of primary, ABO‐compatible LT performed between 2001 and 2010. Recipients were stratified in four groups based on donor age (<60 years; 60–69 years; 70–79 years and ≥80 years) and their outcomes were compared. A total of 842 patients were included: 348 (41.3%) with donors <60 years; 176 (20.9%) with donors 60–69 years; 233 (27.7%) with donors 70–79 years and 85 (10.1%) with donors ≥80 years. There was no difference across groups in terms of early (≤30 days) graft loss, and graft survival at 1 and 5 years was 90.5% and 78.6% for grafts <60 years; 88.6% and 81.3% for grafts 60–69 years; 87.6% and 75.1% for grafts 70–79 years and 84.7% and 77.1% for grafts ≥80 years (p = 0.065). In the group ≥80 years, the 5‐year graft survival was lower for HCV‐positive versus HCV‐negative recipients (62.4% vs. 85.6%, p = 0.034). Based on our experience, grafts from donors ≥80 years may provide favorable results but require appropriate selection and allocation policies.

Use of fenoldopam to control renal dysfunction early after liver transplantation.

With the aim of assessing whether fenoldopam can help to preserve renal function after liver transplantation, we randomized 140 consecutive recipients with comparable preoperative renal function to receive fenoldopam 0.1 μg/kg/minute (group F, 46 patients), dopamine 3 μg/kg/minute (group D, 48 patients), or placebo (group P, 46 patients) from the time of anesthesia induction to 96 hours postoperatively. There were no differences between the groups in intraoperative urinary output or furosemide administration (both P = .1). Daily recordings made during the first 4 postoperative days revealed no significant differences in urinary output (P = .1), serum creatinine (P = .5), the incidence of renal insufficiency (P = .7), the need for loop diuretics (P = .9) or vasoactive drugs (P = .8). In comparison with preoperative levels, creatinine clearance at the end of the study in the patients receiving fenoldopam remained substantially unchanged, whereas it decreased by 39 and 12.3%, respectively, in the subjects receiving placebo or dopamine (P < .001); blood cyclosporine A (CsA) levels were similar in the 3 groups (P = .1). Three subjects died in the intensive care unit (1 in each group, P = .9), 2 of them had renal failure. In conclusion, our results confirm the inefficacy of dopamine in preventing or limiting early renal dysfunction after liver transplantation, and suggest that fenoldopam may preserve creatinine clearance by counterbalancing the renal vasoconstrictive effect of CsA, as it has been reported in previous experimental studies. (Liver Transpl 2004;10:986–992.)

Continuous right ventricular end diastolic volume and right ventricular ejection fraction during liver transplantation: A multicenter study†

Cardiac preload is traditionally considered to be represented by its filling pressures, but more recently, estimations of end diastolic volume of the left or right ventricle have been shown to better reflect preload. One method of determining volumes is the evaluation of the continuous right ventricular end diastolic volume index (cRVEDVI) on the basis of the cardiac output thermodilution technique. Because preload and myocardial contractility are the main factors determining cardiac output during liver transplantation (LTx), accurate determination of preload is important. Thus, monitoring of cRVEDVI and cRVEF should help with fluid management and with the assessment of the need for inotropic and vasoactive agents. In this multicenter study, we looked for possible relationships between the stroke volume index (SVI) and cRVEDVI, cRVEF, and filling pressures at 4 predefined steps in 244 patients undergoing LTx. Univariate and multivariate autoregression models (across phases of the surgical procedure) were fitted to assess the possible association between SVI and cRVEDVI, pulmonary artery occlusion pressure (PAOP), and central venous pressure (CVP) after adjustment for cRVEF (categorized as ≤30, 31–40, and >40%). SVI was strongly associated with both cRVEDVI and cRVEF. The model showing the best fit to the data was that including cRVEDVI. Even after adjustment for cRVEF, there was a statistically significant (P < 0.05) relationship between SVI and cRVEDVI with a regression coefficient (slope of the regression line) of 0.25; this meant that an increase in cRVEDVI of 1 mL m−2 resulted in an increase in SVI of 0.25 mL m−2. The correlations between SVI and CVP and PAOP were less strong. We conclude that cRVEDVI reflected preload better than CVP and PAOP. Liver Transpl 14:327–332, 2008.

Fever, mental impairment, acute anemia, and renal failure in patient undergoing orthotopic liver transplantation: Posttransplantation malaria

A case of post‐transplant malaria is described. The patient presented fever and severe anemia after orthotopic liver transplantation. Diagnosis was made only after the review of donor characteristics. Although a high parasitemia was found at the moment of diagnosis, the treatment with quinine and doxycycline was successful. Donor epidemiology should always be considered for a prompt diagnosis of rare tropical diseases in the graft recipients. Liver Transpl 12:674–676, 2006.

Stress-inducing factors in ICUs: What liver transplant recipients experience and what caregivers perceive

The aim of this study was to compare a number of potentially stress‐generating factors related to an intensive care unit (ICU) stay from the points of view of patients undergoing liver transplantation or elective major abdominal surgery and their caregivers in order to identify differences and similarities that may help to optimize patient care. The ICU Environmental Stressor Scale questionnaire was administered to 104 liver transplant recipients, 103 major abdominal surgery patients, 35 nurses and 21 physicians. The ICU staff were asked to complete the questionnaire on the basis of their perception of patient stressors. Both patient groups identified Being unable to sleep, Being in pain, Having tubes in nose/mouth, Missing husband/wife, and Seeing family and friends only a few minutes a day as the major stressors; the healthcare providers correctly identified the most stressing factors for the patients, but gave them higher scores. The mean scores were 71.9 ± 18.7 for the transplant recipients, 66.3 ± 20.9 for the patients undergoing elective major abdominal surgery, 99.7 ± 19.2 for the nurses, and 92.7 ± 16.1 for the physicians (P < 0.001). The qualitative evaluations of potentially stress‐inducing ICU situations were substantially the same in the 2 patient groups, but the transplant recipients seemed to feel them more acutely. Although the caregivers identified the most discomforting situations, they overestimated the degree of stress they cause. The staff of each ICU should therefore seek to understand and reduce (even by means of simple interventions) the particular causes of psychophysical stress felt by their patients. (Liver Transpl 2005;11:967–972.)