Liver transplantation versus watchful waiting in hepatocellular carcinoma patients with complete response to bridging therapy - a retrospective observational study.

Bridging therapy to prevent progression on the waiting list can result in a sustained complete response (sCR). In some patients, the liver transplantation (LT) risk might exceed those of tumor recurrence. We thus evaluated whether a watchful waiting (CR-WW) strategy could be a feasible alternative to transplantation (CR-LT). We performed a retrospective analysis of overall survival (OS) and recurrence-free survival (RFS) of patients with a sCR (CR > 6 months). Permitted bridging included thermoablation, resection, and combinations of either with transarterial chemoembolization. Patients were divided into the intended treatment strategies CR-WW and CR-LT. 39 (18.40%) sCR patients from 212 were investigated. 22 patients were treated with a CR-LT and 17 patients a CR-WW strategy. Five-year RFS was lower in the CR-WW than in the CR-LT group [53.3% (22.1%; 77.0%) and 84.0% (57.6%; 94.7%)]. 29.4% (5/17) CR-WW patients received salvage transplantation because of recurrence. OS (5-year) was 83.9% [56.8%; 94.7%] after LT and 75.4% [39.8%; 91.7%] after WW. Our analysis shows that the intuitive decision made by our patients in agreement with their treating physicians for a watchful waiting strategy in sCR can be justified. Applied on a larger scale, this strategy could help to reduce the pressure on the donor pool.

Elevated cardiac troponin T in cirrhotic patients with emergency care admissions: Associations with mortality.

BACKGROUND AND AIM: Mortality of cirrhotic patients after emergency care admission is high, and prognostic factors can help in prioritizing patients. The aim of our study was to assess the association between levels of cardiac troponin T (cTnT) and 1-year mortality in patients with liver cirrhosis without known cardiac disease, who were admitted to the emergency department (ED). METHODS: All patients with cirrhosis presented to the ED from October 2009 until August 2015 who had an initial cTnT value measured with the first lab panel were retrospectively analyzed with a follow-up of 365 days. RESULTS: Of a total of 237 cirrhotic ED patients, cTnT measurements were available for 87 (63% men, mean age 58.9 ± 11.0 years, and median Model for End-stage Liver Disease score was 15 [25th-75th percentile: 10-19]). Chronic Liver Failure Consortium acute-on-chronic liver failure (CLIF-C-ACLF) score was 33. Forty-three patients (49%) had cTnT values above the normal range (14 ng/L), of which 19 (22%) had values over 30 ng/L. Two patients were lost to follow-up. In multivariable analysis, both CLIF-C-ACLF (hazard ratio 1.072 per point increase; 95% confidence interval 1.029-1.117; P < 0.001) and cTnT (hazard ratio 1.014 per ng/L increase; 95% confidence interval 1.004-1.024; P = 0.008) emerged as independently associated with mortality. CONCLUSIONS: A large proportion of cirrhotic patients in the ED have elevated levels of cTnT even if there is no evidence of cardiac disease. Elevated cTnT is associated with increased mortality during 1 year after correcting for Model for End-stage Liver Disease and CLIF-C-ACLF scores.

Infection and Predictors of Outcome of Cirrhotic Patients after Emergency Care Hospital Admission.

INTRODUCTION AND AIMS: We aimed to explore the impact of infection diagnosed upon admission and of other clinical baseline parameters on mortality of cirrhotic patients with emergency admissions. MATERIAL AND METHODS: We performed a prospective observational monocentric study in a tertiary care center. The association of clinical parameters and established scoring systems with short-term mortality up to 90 days was assessed by univariate and multivariable Cox regression analysis. Akaike's Information Criterion (AIC) was used for automated variable selection. Statistical interaction effects with infection were also taken into account. RESULTS: 218 patients were included. 71.2% were male, mean age was 61.1 ± 10.5 years. Mean MELD score was 16.2 ± 6.5, CLIF-consortium Acute on Chronic Liver Failure-score was 34 ± 11. At 28, 90 and 365 days, 9.6%, 26.0% and 40.6% of patients had died, respectively. In multivariable analysis, respiratory organ failure [Hazard Ratio (HR) = 0.15], albumin substitution (HR = 2.48), non-HCC-malignancy (HR = 4.93), CLIF-C-ACLF (HR = 1.10), HCC (HR = 3.70) and first episode of ascites (HR = 0.11) were significantly associated with 90-day mortality. Patients with infection had a significantly higher 90-day mortality (36.3 vs. 20.1%, p = 0.007). Cultures were positive in 32 patients with resistance to cephalosporins or quinolones in 10, to ampicillin/sulbactam in 14 and carbapenems in 6 patients. CONCLUSION: Infection is common in cirrhotic ED admissions and increases mortality. The proportion of resistant microorganisms is high. The predictive capacity of established scoring systems in this setting was low to moderate.

Disparities in Eurotransplant liver transplantation wait-list outcome between patients with and without model for end-stage liver disease exceptions.

The sickest-first principle in donor-liver allocation can be implemented by allocating organs to patients with cirrhosis with the highest Model for End-Stage Liver Disease (MELD) scores. For patients with other risk factors, standard exceptions (SEs) and nonstandard exceptions (NSEs) have been developed. We investigated whether this system of matched MELD scores achieves similar outcomes on the liver transplant waiting list for various diagnostic groups in Eurotransplant (ET) countries with MELD-based individual allocation (Belgium, the Netherlands, and Germany). A retrospective analysis of the ET wait-list outflow from December 2006 until December 2015 was conducted to investigate the relation of the unified MELD-based allocation to the risk of a negative wait-list outcome (death on the waiting list or delisting as too sick) as opposed to a positive wait-list outcome (transplantation or delisting as recovered). A total of 16,926 patients left the waiting list with a positive (11,580) or negative (5346) outcome; 3548 patients had a SE, and 330 had a NSE. A negative outcome was more common among patients without a SE or NSE (34.3%) than among patients with a SE (22.6%) or NSE (18.6%; P < 0.001). Analysis by model-based recursive partitioning detected 5 risk groups with different relations of matched MELD to a negative outcome. In Germany, we found the following: (1) no SE or NSE, SE for biliary sepsis (BS); (2) SE for hepatocellular carcinoma (HCC), hepatopulmonary syndrome (HPS), or portopulmonary hypertension (PPH); and (3) SE for primary sclerosing cholangitis (PSC) or polycystic liver disease (PcLD). In Belgium and the Netherlands, we found the following: (4) SE or NSE, or SE for HPS or PPH; and (5) SE for BS, HCC, PcLD, or PSC. In conclusion, SEs and NSEs do not even out risks across different diagnostic groups. Patients with SEs or NSEs appear advantaged toward patients with cirrhosis without SEs or NSEs. Liver Transplantation 23 1256-1265 2017 AASLD.

Liver transplantation followed by autologous stem cell transplantation for acute liver failure caused by AL amyloidosis. Case report and review of the literature.

 Hepatic involvement in AL amyloidosis may present as acute liver failure. Historically, liver transplantation in these cases has achieved poor outcomes due to progress of amyloidosis and non-hepatic organ damage. In the era of bortezomib treatment, the prognosis of AL amyloidosis has been markedly improved and may also result in better post-transplant outcomes. We present a case of isolated acute liver failure caused by AL amyloidosis, bridged to transplantation with bortezomib and treated with sequential orthotopic liver transplantation (OLT) and autologous stem cell transplantation. The patient is in stable remission 3 years after OLT.

Donor organ distribution according to urgency of need or outcome maximization in liver transplantation. A questionnaire survey among patients and medical staff.

Low donor rates in Germany cause a trade-off between equity in the distribution of chances for survival and efficiency in dead-donor liver transplantation. Public attitudes concerning the principles that should govern organ allocation are of interest. We performed a questionnaire-based study among patients and medical staff. 1826 of 2200 questionnaires were returned. 79.2%, 67.1%, and 24.4% patients wanted to accept liver transplantation for themselves if expected 1-year survival was 80%, 50%, and 20%, respectively. 57.7% affirmed 'averting immediate risk of death (urgency) is a more important criterion for organ allocation than expected long-term success' (P = 0.002 against indifference). The majority of medical staff took the opposite decision. 20.7%, 8.8%, and 21.2% of patients chose 50%, 33%, and 10% as lowest acceptable 5-year survival, respectively. 49.3% accepted a survival of <10%. Variables associated with preferring urgency over efficiency as criterion for allocation were age (OR 1.009; 95% CI: 1.000-1.017; female gender (OR 1.331; 95%CI 0.992-1.784); higher education (OR 0.881; 95%CI 0.801-0.969); and refusal of transplantation for oneself (OR 1.719; 95%CI 1.272-2.324). Most patients supported urgency-based liver allocation. Patients and medical staff would accept lower survival rates than the transplant community.

Contrast-induced acute kidney injury in cirrhotic patients. A retrospective analysis.

BACKGROUND: The nephrotoxic potential of intravenous iodinated contrast (IC) is controversial. Cirrhotic patients are often submitted to imaging procedures involving IC and small changes in renal function may have detrimental effects. MATERIAL AND METHODS: Retrospective analysis of hospitalized patients with elective imaging by either contrast-enhanced CT or MRI. Contrast induced acute kidney injury (CI-AKI) was diagnosed if there was either an increase of SCr by 25% or by 44 µmol/L or a decrease of estimated glomerular filtration rate by 25% by day 3. RESULTS: Between 2004 and 2012 152 patients (female: 30.3%, age: 60 ± 10.8 years, MELD 13 ± 6) were included in this study of which 84 (55.3%) had received IC and 68 (44,7%), who served as controls, MRI with gadolinium based contrast (non-IC). Baseline parameters were well matched except for age (61.7 vs. 56.9) years in the IC vs. non-IC groups, p = 0.005). 15 patients (17.9%) receiving IC and 4 patients (5.9%) not receiving IC (p = 0.026) reached the composite end-point for CI-AKI. In multivariable regression analysis INR [B = 0.252 (95% CI: 0.108-0.397), p = 0.001]; IC [B = 0.136 (95% CI: 0.023-0.248), p = 0.019] and serum sodium [B = 0.011 (95% CI: 0.001-0.023); p = 0.080] were independently associated with changes of SCr. In conclusion IC may cause renal dysfunction in cirrhotic patients. Patients subjected to imaging using IC should be closely monitored.

How to diagnose hepatic encephalopathy in the emergency department.

INTRODUCTION: Blood ammonia-measurements are often performed in the emergency departments to diagnose or rule out hepatic encephalopathy (HE). However, the utility and correct interpretation of ammonia levels is a matter of discussion. At this end the present prospective study evaluated whether blood ammonia levels coincide with HE which was also established by the West Haven criteria and the critical flicker frequency, respectively. MATERIAL AND METHODS: In 59 patients with known cirrhosis ammonia-levels were determined and patient were additionally categorized by the West-Haven criteria and were also evaluated psychophysiologically using the critical flicker frequency, CFF for the presence of HE. RESULTS: When false positive and false negative results were collapsed the determination of blood ammonia levels alone resulted in 40.7% in a misdiagnoses of HE compared to the West-Haven criteria (24/59 when using West-Haven criteria, 95% confidence interval [CI], 28.1% to 54.3%) and 49.2% when compared with the results of the CFF (29/59, when using CFF, 95% CI, 35.9% to 62.5%). DISCUSSION: Ammonia blood levels do not reliably detect HE and the determination of blood ammonia can not be regarded a useful screening test for HE. Its use as sole indicator for a HE in the Emergency Department may frequently result in frequent misinterpretations.

Do patients referred to emergency departments after being assessed in primary care differ from other ED patients? Retrospective analysis of a random sample from two German metropolitan EDs.

BACKGROUND: To assess differences between patients referred to emergency departments by a primary care physician (PCP) and those presenting directly and the impact of referral on the likelihood of admission. DESIGN OF STUDY: Retrospective cohort study. SETTING: EDs of two nonacademic general hospitals in a German metropolitan region. PARTICIPANTS: Random sample of 1500 patients out of 80,845 presentations during the year 2019. RESULTS: Age was 55.8 ± 22.9 years, and 51.4% was female. A total of 34.7% presented by emergency medical services (EMS), and 47.7% were walk-ins. One-hundred seventy-four (11.9%) patients were referred by PCPs. Referrals were older (62.4 ± 20.1 vs 55.0 ± 23.1 years, p < .001) and had a higher Charlson Comorbidity Index (CCI) (3 (1-5) vs 2 (0-4); p < .001). Referrals received more ultrasound examinations independently from their admission status (27.6% vs 15.7%; p < .001) and more CT and laboratory investigations. There were no differences in sex, Manchester Triage System (MTS) category, or pain-scale values. Referrals presented by EMS less often (9.2% vs 38.5%; p < .001). Admission rates were 62.6% in referrals and 37.1% in non-referrals (p < .001). Referral (OR 3.976 95% CI: 2.595-6.091), parenteral medication in ED (OR 2.674 (1.976-3.619)), higher MTS category (1.725 (1.421-2.093)), transport by EMS (1.623 (1.212-2.172)), abnormal vital parameters (1.367 (0.953-1.960)), higher CCI (1.268 (1.196-1.344)), and trauma (1.268 (1.196-1.344)) were positively associated with admission in multivariable analysis, whereas ultrasound in ED (0.450 (0.308-0.658)) and being a nursing home resident (0.444 (0.270-0.728)) were negatively associated. CONCLUSION: Referred patients were more often admitted. They received more laboratory investigations, ultrasound examinations, and computed tomographies. Difficult decisions regarding the necessity of admission requiring typical resources of EDs may be a reason for PCP referrals.

Etiologies and outcomes of acute liver failure in Germany.

BACKGROUND & AIMS: Acute liver failure (ALF) is a severe form of acute liver injury that can progress to multiple organ failure. We investigated causes and outcomes of ALF. METHODS: Eleven university medical centers in Germany were asked to report patients with (primary) severe acute liver injury (sALI) (international normalized ratio [INR] >1.5 but no hepatic encephalopathy) and primary ALF (INR >1.5 with overt hepatic encephalopathy) treated from 2008 to 2009. Data were analyzed from 46 patients with sALI and 109 patients with ALF. RESULTS: The most frequent etiologies of primary ALF were non-acetaminophen drug-induced (32%), indeterminate (24%), and viral (21%); acetaminophen ingestion was the cause of ALF in only 9% of patients. The support of a ventilator was required by 44% of patients with ALF, vasopressors by 38%, and renal replacement by 36%. Seventy-nine patients with ALF (72%) survived until hospital discharge, 38 (35%) survived without emergency liver transplantation (ELT), and 51 received ELT (47%); 80% of patients who received ELT survived until discharge from the hospital. CONCLUSIONS: In Germany, drug toxicity, indeterminate etiology, and viral hepatitis appear to be the major causes of primary ALF, which has high mortality. Patients with ALF are at great risk of progressing to multiple organ failure, but 80% of patients who receive ELT survive until discharge from the hospital.

Renal and circulatory effects of large volume plasma expansion in patients with hepatorenal syndrome type 1.

INTRODUCTION: Hepatorenal syndrome type I (HRS I) may be a consequence of circulatory dysfunction in cirrhotic patients with portal hypertension. This uncontrolled interventional pilot study examines the hemodynamic and renal effects of large volume plasma expansion in HRS I. MATERIAL AND METHODS: 14 cirrhotic patients (8 m, 6 f, age 60 (58-65) years) with HRS I received large volume plasma expansion with up to 400 mL of 20% human albumin solution per 12 over 48 h under hemodynamic monitoring by transpulmonary thermodilution. Creatinine clearances (ClCreat) were calculated for 12-h periods. Plasma expansion was withheld if criteria of volume overload [Extravascular lung Water Index (ELWI) > 9 mL/kg or Global End-Diastolic Volume Index (GEDI) > 820 mL/m(2)] were met. Paracentesis was performed according to clinical necessity and treatment continued for 48 h thereafter. Serum creatinine values were observed for 12 days. RESULTS: Patients received 1.6 (1.5-2.0) g of albumin per kg bodyweight and day for 48 to 96 h. During the treatment period, GEDVI [724 (643-751) mL/m(2) vs. 565 (488-719) mL/m(2) ; p = 0.001], cardiac index (CI) [4.9 (4.1-6.15) L/min/m(2) vs. 3.9 (3.4-5.0) L /min/m(2) ; p = 0.033], urinary output [25 (17-69) mL/h vs. 17 (8-39) mL/h; p = 0.016) and ClCreat [20 (15-47) vs. 12 (6-17); p = 0.006] increased whereas systemic vascular resistance index (SVRI), plasma renin activity (PRA) and plasma aldosterone were significantly reduced. At 48 h there were two complete responses (serum creatinine < 133 µmol/L) and on day 12, 8 patients had a complete response. CONCLUSION: HRS I may respond to large volume plasma expansion with or without paracentesis.

High rate of complete histopathological response in hepatocellular carcinoma patients after combined transarterial chemoembolization and stereotactic body radiation therapy.

BACKGROUND: Liver transplantation (LT) presents a curative treatment option in patients with early stage hepatocellular carcinoma (HCC) who are not eligible for resection or ablation therapy. Due to a risk of up 30% for waitlist drop-out upon tumor progression, bridging therapies are used to halt tumor growth. Transarterial chemoembolization (TACE) and less commonly stereotactic body radiation therapy (SBRT) or a combination of TACE and SBRT, are used as bridging therapies in LT. However, it remains unclear if one of those treatment options is superior. The analysis of explant livers after transplantation provides the unique opportunity to investigate treatment response by histopathology. AIM: To analyze histopathological response to a combination of TACE and SBRT in HCC in comparison to TACE or SBRT alone. METHODS: In this multicenter retrospective study, 27 patients who received liver transplantation for HCC were analyzed. Patients received either TACE or SBRT alone, or a combination of TACE and SBRT as bridging therapy to liver transplantation. Liver explants of all patients who received at least one TACE and/or SBRT were analyzed for the presence of residual vital tumor tissue by histopathology to assess differences in treatment response to bridging therapies. Statistical analysis was performed using Fisher-Freeman-Halton exact test, Kruskal-Wallis and Mann-Whitney-U tests. RESULTS: Fourteen patients received TACE only, four patients SBRT only, and nine patients a combination therapy of TACE and SBRT. There were no significant differences between groups regarding age, sex, etiology of underlying liver disease or number and size of tumor lesions. Strikingly, analysis of liver explants revealed that almost all patients in the TACE and SBRT combination group (8/9, 89%) showed no residual vital tumor tissue by histopathology, whereas TACE or SBRT alone resulted in significantly lower rates of complete histopathological response (0/14, 0% and 1/4, 25%, respectively, P value < 0.001). CONCLUSION: Our data suggests that a combination of TACE and SBRT increases the rate of complete histopathological response compared to TACE or SBRT alone in bridging to liver transplantation.

Transpulmonary thermodilution using femoral indicator injection: a prospective trial in patients with a femoral and a jugular central venous catheter.

INTRODUCTION: Advanced hemodynamic monitoring using transpulmonary thermodilution (TPTD) is established for measurement of cardiac index (CI), global end-diastolic volume index (GEDVI) and extra-vascular lung water index (EVLWI). TPTD requires indicator injection via a central venous catheter (usually placed via the jugular or subclavian vein). However, superior vena cava access is often not feasible due to the clinical situation. This study investigates the conformity of TPTD using femoral access. METHODS: This prospective study involved an 18-month trial at a medical intensive care unit at a university hospital. Twenty-four patients with both a superior and an inferior vena cava catheter at the same time were enrolled in the study. RESULTS: TPTD-variables were calculated from TPTD curves after injection of the indicator bolus via jugular access (TPTDjug) and femoral access (TPTDfem). GEDVIfem and GEDVIjug were significantly correlated (rm = 0.88; P < 0.001), but significantly different (1,034 +/- 275 vs. 793 +/- 180 mL/m2; P < 0.001). Bland-Altman analysis demonstrated a bias of +241 mL/m2 (limits of agreement: -9 and +491 mL/m2). GEDVIfem, CIfem and ideal body weight were independently associated with the bias (GEDVIfem-GEDVIjug). A correction formula of GEDVIjug after femoral TPTD, was calculated. EVLWIfem and EVLWIjug were significantly correlated (rm = 0.93; P < 0.001). Bland-Altman analysis revealed a bias of +0.83 mL/kg (limits of agreement: -2.61 and +4.28 mL/kg). Furthermore, CIfem and CIjug were significantly correlated (rm = 0.95; P < 0.001). Bland-Altman analysis demonstrated a bias of +0.29 L/min/m2 (limits of agreement -0.40 and +0.97 L/min/m2; percentage-error 16%). CONCLUSIONS: TPTD after femoral injection of the thermo-bolus provides precise data on GEDVI with a high correlation, but a self-evident significant bias related to the augmented TPTD-volume. After correction of GEDVIfem using a correction formula, GEDVIfem shows high predictive capabilities for GEDVIjug. Regarding CI and EVLWI, accurate TPTD-data is obtained using femoral access.

Effects of TIPS on global end-diastolic volume and cardiac output and renal resistive index in ICU patients with advanced alcoholic cirrhosis.

The transjugular porto-systemic stent-shunt (TIPS) reduces portal pressure in cirrhotic patients and is used as a nonsurgical treatment for refractory ascites, recurrent variceal hemorrhage or hepatorenal syndrome. There are concerns regarding a negative impact on cirrhotic cardiomyopathy and deterioration of hyperkinetic circulatory dysfunction. We analyzed a prospectively maintained database containing hemodynamic data on cirrhotic ICU patients. Hemodynamic monitoring was performed using transpulmonary thermodilution (PiCCO, Pulsion Medical Systems, Munich, Germany). Renal perfusion was assessed by Doppler ultrasound during studies of portal and TIPS perfusion before and after the procedure. Complete data sets of 8 patients (4 male, 4 female, age 60 years (52-67), Child-Pugh-Turcotte score 10 (8-12)) were available. After TIPS, there was a substantial increase of GEDVI (646 ml/m2 (580-737) to 663 mL/m2 (643-792); p=0.036) that was even more pronounced at 24 hours (716 mL/m2 (663-821); P=0.012). CI increased from 3.3 L/min/m2 (3.1-4.2) to 3.9 L/min/m2 (3.6-5.3) (p=0.012) and 3.9 L/min/m2 (3.7-5.2) (p=0.017), respectively. There was a significant decrease of renal RI from 0.810 (0.781-0.864) to 0.746 (0.710-0.798) (p=0.028) and a transient increase of fractional excretion of sodium. SVRI (1737 dyn*s/cm5/m2 (1088 . 2115) vs. 1917 dyn*s/cm5/m2 (1368-2177) was not significantly altered immediately after TIPS but decreased to 1495 dyn*s/cm5/m2 (833- 1765) at 24 hours (p=0.036). There were no significant changes of mean arterial pressure (MAP). In conclusion, TIPS resulted in a pronounced increase of central blood volume. The observed hemodynamic effects are compatible with a preload driven increase of cardiac output and secondary decreases in SVRI and RI.

Prognostic factors in hepatocellular carcinoma patients undergoing transarterial chemoembolization and radioembolization: a retrospective study.

OBJECTIVE: Most patients with hepatocellular carcinoma are diagnosed at intermediate or advanced stages (BCLC B or C) and undergo palliative local treatments such as transarterial chemoembolization or selective internal radiation therapy, also called radioembolization. In terms of liver function and tumor extent, stages BCLC B and C comprise a wide spectrum of tumor manifestations. Predictors of survival in these patients undergoing transarterial chemoembolization and selective internal radiation therapy might help stratification into different prognostic groups and help to select the optimal treatment modality. METHODS: In this retrospective study, all patients with hepatocellular carcinoma who underwent transarterial chemoembolization between January 2010 and December 2014 and all hepatocellular carcinoma patients who underwent selective internal radiation therapy between August 2012 and December 2016 were recruited. The prognostic value of pretherapeutic clinical and laboratory parameters for the prediction of overall survival was analyzed using uni- and multi-variable Cox regression models. RESULTS: We enrolled 129 patients in the transarterial chemoembolization group and 34 patients in the selective internal radiation therapy group. The predictive value of the albumin-bilirubin grade was validated for both the transarterial chemoembolization and the selective internal radiation therapy group. Multivariable analysis identified albumin-bilirubin grade and tumor size as independent predictors for the transarterial chemoembolization group and tumor size, serum albumin and serum sodium as independent predictors for the selective internal radiation therapy group. CONCLUSION: While measures of liver dysfunction predicted survival similarly in both cohorts, we found tumor size to predict survival differently in transarterial chemoembolization- and selective internal radiation therapy-treated patients. Tumor size might help to select the most appropriate treatment in hepatocellular carcinoma patients, although this finding has to be validated in further studies.

Volume assessment in patients with necrotizing pancreatitis: a comparison of intrathoracic blood volume index, central venous pressure, and hematocrit, and their correlation to cardiac index and extravascular lung water index.

OBJECTIVE: Volume depletion and/or increased hematocrit are associated with poor prognosis in necrotizing pancreatitis. Several studies suggest that intrathoracic blood volume index (ITBI) might be superior to central venous pressure (CVP) with regard to preload assessment. Therefore, the aim of our study was to evaluate the predictive value of CVP and hematocrit with regard to ITBI, and to correlate these parameters to cardiac index (CI). DESIGN: Prospective study. SETTING: Medical intensive care unit, university hospital. PATIENTS AND INTERVENTIONS: Within 24 hrs of intensive care unit-admission, 96 hemodynamic measurements using the PiCCO system were performed in 24 patients with necrotizing pancreatitis. MAIN RESULTS: Mean CVP (12.11 +/- 5.97 mm Hg; median 11.5 normal: 1-9 mm Hg) was elevated, whereas mean ITBI (822.8 +/- 157.0 mL/m2; median 836 mL/m2; normal: 850-1000 mL/m2) was decreased. Fifty-one of 96 ITBI values were decreased (prevalence of hypovolemia of 53%). No CVP value was decreased. Fifty-three CVP measurements were elevated despite simultaneous ITBI levels indicating a normal or decreased preload. Sensitivity, specificity, positive predictive value, and negative predictive value of CVP with regard to volume depletion (ITBI <850 mL/m2), were 0%, 100%, 0%, and 47%, respectively. An increase in hematocrit (hematocrit >40% [female] or >44% [male]) was found in 11 of 51 measurements with decreased ITBI. Sensitivity, specificity, positive predictive value, and negative predictive value of an increase in hematocrit with regard to volume depletion according to ITBI were 22%, 82%, 58%, and 48%, respectively. ITBI and delta-ITBI significantly correlated to CI and delta-CI (r = .566, p < 0.001; r = .603, p < 0.001), respectively. CVP and delta-CVP did not correlate to CI and delta-CI, respectively. There was a significant correlation between ITBI and extravascular lung water index (r = .392; p < 0.001), but no correlation between CVP and extravascular lung water index (r = .074; p = 0.473). CONCLUSIONS: Volume depletion according to ITBI was found in more than half the patients. The predictive values of CVP and hematocrit with regard to volume depletion were low. ITBI and its changes significantly correlated to CI and its changes, which was not observed for CVP and delta-CVP. Therefore, ITBI appears to be more appropriate for volume management in necrotizing pancreatitis than CVP or hematocrit.

Haemodynamic effects of plasma-expansion with hyperoncotic albumin in cirrhotic patients with renal failure: a prospective interventional study.

BACKGROUND: Patients with advanced cirrhosis of the liver typically display circulatory disturbance. Haemodynamic management may be critical for avoiding and treating functional renal failure in such patients. This study investigated the effects of plasma expansion with hyperoncotic albumin solution and the role of static haemodynamic parameters in predicting volume responsiveness in patients with advanced cirrhosis. METHODS: Patients with advanced cirrhosis (Child B and C) of the liver receiving albumin substitution because of renal compromise were studied using trans-pulmonary thermodilution. Paired measurements before and after two infusions of 200 ml of 20% albumin per patient were recorded and standard haemodynamic parameters such as central venous pressure (CVP), mean arterial pressure (MAP), systemic vascular resistance index (SVRI), cardiac index (CI) and derived variables were assessed, including global end-diastolic blood volume index (GEDVI), a parameter that reflects central blood volume RESULTS: 100 measurements in 50 patients (33 m/17 w; age 56 years (+/- 8); Child-Pugh-score 12 (+/- 2), serum creatinine 256 micromol (+/- 150) were analyzed. Baseline values suggested decreased central blood volumes GEDVI = 675 ml/m2 (+/- 138) despite CVP within the normal range (11 mmHg (+/- 5). After infusion, GEDVI, CI and CVP increased (682 ml/m2 (+/- 128) vs. 744 ml/m2 (+/- 171), p < 0.001; 4.3 L/min/m2 (+/- 1.1) vs. 4.7 L/min/m2 (+/- 1.1), p < 0.001; 12 mmHg (+/- 6) vs. 14 mmHg (+/- 6), p < 0.001 respectively) and systemic vascular resistance decreased (1760 dyn s/cm5/m2 (+/- 1144) vs. 1490 dyn s/cm5/m2 (+/- 837); p < 0.001). Changes in GEDVI, but not CVP, correlated with changes in CI (r2 = 0.51; p < 0.001). To assess the value of static haemodynamic parameters at baseline in predicting an increase in CI of 10%, receiver-operating-characteristic curves were constructed. The areas under the curve were 0.766 (p < 0.001) for SVRI, 0.723 (p < 0.001) for CI, 0.652 (p = 0.010) for CVP and 0.616 (p = 0.050) for GEDVI. CONCLUSION: In a substantial proportion of patients with advanced cirrhosis, plasma expansion results in an increase in central blood volume. GEDVI but not CVP behaves as an indicator of cardiac preload, whereas high baseline SVRI is predictive of fluid responsiveness.

Effects of plasma expansion with albumin and paracentesis on haemodynamics and kidney function in critically ill cirrhotic patients with tense ascites and hepatorenal syndrome: a prospective uncontrolled trial.

INTRODUCTION: Circulatory dysfunction in cirrhotic patients may cause a specific kind of functional renal failure termed hepato-renal syndrome (HRS). It contributes to the high incidence of renal failure in cirrhotic intensive care unit (ICU) patients. Fluid therapy may aggravate renal failure by increasing ascites and intra-abdominal pressure (IAP). This study investigates the short-term effects of paracentesis on haemodynamics and kidney function in volume resuscitated patients with HRS. METHODS: Nineteen consecutive cirrhotic patients with HRS were studied. Circulatory parameters and renal function were analysed before and after plasma expansion and paracentesis. Haemodynamic monitoring was performed by transpulmonary thermodilution. RESULTS: After infusion of 200 ml of 20% human albumin solution, mean arterial pressure (MAP) and central venous pressure remained unchanged. Global end-diastolic volume index (GEDVI) increased from 791 ml m(-2) (693 to 862) (median and 25th to 75th percentile) to 844 ml m(-2) (751 to 933). Cardiac index (CI) increased from 4.1 l min(-1) m(-2) (3.6 to 5.0) to 4.7 l min(-1) m(-2) (4.0 to 5.8), whereas systemic vascular resistance index (SVRI) decreased from 1,422 dyn s cm(-5) m(-2) (1,081 to 1,772) to 1,171 dyn s cm(-5) m(-2) (893 to 1,705). Creatinine clearance (CC) and fractional excretion of sodium (FeNa) were not affected. During paracentesis, IAP decreased from 22 mmHg (18 to 24) to 9 mmHg (8 to 12). MAP decreased from 81 mmHg (74 to 100) to 80 mmHg (71 to 89), and CI increased from 4.1 l min(-1) m(-2) (3.2 to 4.3) to 4.2 l min(-1) m(-2) (3.6 to 4.7), whereas SVRI decreased from 1,639 dyn s cm(-5) m(-2) (1,168 to 2,037) to 1,301 dyn s cm(-5) m(-2) (1,124 to 1,751). CC during the 12-hour interval after paracentesis was significantly higher than during the 12 hours before (33 ml min(-1) (16 to 50) compared with 23 ml min(-1) (12 to 49)). CC remained elevated for the rest of the observation period. FeNa increased after paracentesis but returned to baseline levels after 24 hours. CONCLUSION: Paracentesis with parameter-guided fluid substitution and maintenance of central blood volume may improve renal function and is safe in the treatment of ICU patients with hepato-renal failure.