Peter Schenk

Hypoxic hepatitis: underlying conditions and risk factors for mortality in critically ill patients.

PurposeHypoxic hepatitis (HH) is a frequent cause of acute hepatocellular damage at the intensive care unit. Although mortality is reported to be high, risk factors for mortality in this population are unknown.MethodsOne-hundred and seventeen consecutive patients with HH were studied prospectively at three medical intensive care units of a university hospital.ResultsThe main causes of hypoxic hepatitis were low cardiac output and septic shock, and most patients (74%) had more than one underlying factor. Peak aspartate transaminase (Pxa0=xa00.02), lactate dehydrogenase (Pxa0=xa00.03), INR (Pxa0<xa00.001) and lactate (Pxa0<xa00.01) were higher in non-survivors. Prolonged duration of HH caused higher overall mortality rate (Pxa0=xa00.03). INRxa0>xa02 (Pxa0=xa00.02), septic shock (Pxa0=xa00.01) and SOFA score >10 (Pxa0=xa00.04) were risk factors of mortality in the regression model.ConclusionsHypoxic hepatitis is the consequence of multiorgan injury. Outcome is influenced by the severity of liver impairment and the etiology and severity of the basic disease.

Impact of hypoxic hepatitis on mortality in the intensive care unit

PurposeHypoxic hepatitis (HH) is a form of hepatic injury following arterial hypoxemia, ischemia, and passive congestion of the liver. We investigated the incidence and the prognostic implications of HH in the medical intensive care unit (ICU).MethodsA total of 1,066 consecutive ICU admissions at three medical ICUs of a university hospital were included in this prospective cohort study. All patients were screened prospectively for the presence of HH according to established criteria. Independent risk factors of mortality in this cohort of critically ill patients were identified by a multivariate Poisson regression model.ResultsA total of 118 admissions (11%) had HH during their ICU stay. These patients had different baseline characteristics, longer median ICU stay (8 vs. 6xa0days, pxa0<xa00.001), and decreased ICU survival (43 vs. 83%, pxa0<xa00.001). The crude mortality rate ratio of admissions with HH was 4.62 (95% CI 3.63–5.86, pxa0<xa00.001). Regression analysis demonstrated strong mortality risk for admissions with HH requiring vasopressor therapy (adjusted rate ratio 4.91; 95% CI 2.51–9.60, pxa0<xa00.001), whereas HH was not significantly associated with mortality in admissions without vasopressor therapy (adjusted rate ratio 1.79, 95% CI 0.52–6.23, pxa0=xa00.359).ConclusionsHypoxic hepatitis (HH) occurs frequently in the medical ICU. The presence of HH is a strong risk factor for mortality in the ICU in patients requiring vasopressor therapy.

Von Willebrand factor antigen for detection of hepatopulmonary syndrome in patients with cirrhosis.

BACKGROUND & AIMSnHepatopulmonary syndrome (HPS) occurs in 20-30% of patients with liver cirrhosis and is associated with a >2 fold increased mortality. Endothelial dysfunction seems to play a central role in its pathogenesis. von Willebrand factor antigen (vWF-Ag), an established marker of endothelial dysfunction, is significantly elevated in patients with liver cirrhosis, portal hypertension, and in experimental HPS. Aim of the present study was to evaluate the impact of vWF-Ag as a screening marker for presence of HPS in patients with stable cirrhosis.nnnMETHODSn145 patients with stable liver cirrhosis were screened for presence of HPS in this prospective cohort type cross sectional diagnostic study. vWF-Ag and SaO2 levels were assessed at time of screening for HPS. Criteria of HPS were fulfilled in 31 (21%) patients.nnnRESULTSnvWF-Ag levels were significantly higher in patients with HPS compared to patients without HPS (p<0.001). Furthermore, vWF-Ag correlated significantly with gas exchange in HPS positive patients (p<0.05). vWF-Ag is an independent predictor of HPS after correction for sex, age, model for endstage-liver disease (MELD), and hepatic venous pressure gradient (HVPG) (OR per 1% increase of vWF-Ag: 1.02, 95% CI: 1.00-1.04, p<0.05). The best cut-off was 328% at a sensitivity of 100% and specificity of 53.5%; positive predictive value: 36.9%; negative predictive value: 100%.nnnCONCLUSIONSnHPS is associated with elevated vWF-Ag levels. vWF-Ag may be a useful screening tool for early detection of HPS. Further studies investigating vWF-Ag in HPS will be needed to confirm our findings.

Pharmacokinetics of Ganciclovir during Continuous Venovenous Hemodiafiltration in Critically Ill Patients

ABSTRACT Ganciclovir is an antiviral agent that is frequently used in critically ill patients with cytomegalovirus (CMV) infections. Continuous venovenous hemodiafiltration (CVVHDF) is a common extracorporeal renal replacement therapy in intensive care unit patients. The aim of this study was to investigate the pharmacokinetics of ganciclovir in anuric patients undergoing CVVHDF. Population pharmacokinetic analysis was performed for nine critically ill patients with proven or suspected CMV infection who were undergoing CVVHDF. All patients received a single dose of ganciclovir at 5 mg/kg of body weight intravenously. Serum and ultradiafiltrate concentrations were assessed by high-performance liquid chromatography, and these data were used for pharmacokinetic analysis. Mean peak and trough prefilter ganciclovir concentrations were 11.8 ± 3.5 mg/liter and 2.4 ± 0.7 mg/liter, respectively. The pharmacokinetic parameters elimination half-life (24.2 ± 7.6 h), volume of distribution (81.2 ± 38.3 liters), sieving coefficient (0.76 ± 0.1), total clearance (2.7 ± 1.2 liters/h), and clearance of CVVHDF (1.5 ± 0.2 liters/h) were determined. Based on population pharmacokinetic simulations with respect to a target area under the curve (AUC) of 50 mg · h/liter and a trough level of 2 mg/liter, a ganciclovir dose of 2.5 mg/kg once daily seems to be adequate for anuric critically ill patients during CVVHDF.

Storage of bronchoalveolar lavage fluid and accuracy of microbiologic diagnostics in the ICU: a prospective observational study

IntroductionEarly initiation of appropriate antimicrobial treatment is a cornerstone in managing pneumonia. Because microbiologic processing may not be available around the clock, optimal storage of specimens is essential for accurate microbiologic identification of pathogenetic bacteria. The aim of our study was to determine the accuracy of two commonly used storage approaches for delayed processing of bronchoalveolar lavage in critically ill patients with suspected pneumonia.MethodsThis study included 132 patients with clinically suspected pneumonia at two medical intensive care units of a tertiary care hospital. Bronchoalveolar lavage samples were obtained and divided into three aliquots: one was used for immediate culture, and two, for delayed culture (DC) after storage for 24 hours at 4°C (DC4) and -80°C (DC-80), respectively.ResultsOf 259 bronchoalveolar lavage samples, 84 (32.4%) were positive after immediate culture with 115 relevant culture counts (≥104 colony-forming units/ml). Reduced (<104 colony-forming units/ml) or no growth of four and 57 of these isolates was observed in DC4 and DC-80, respectively. The difference between mean bias of immediate culture and DC4 (-0.035; limits of agreement, -0.977 to 0.906) and immediate culture and DC-80 (-1.832; limits of agreement, -4.914 to 1.267) was -1.788 ± 1.682 (P < 0.0001). Sensitivity and negative predictive value were 96.5% and 97.8% for DC4 and 50.4% and 75.4% for DC-80, respectively; the differences were statistically significant (P < 0.0001).ConclusionsBronchoalveolar lavage samples can be processed for culture when stored up to 24 hours at 4°C without loss of diagnostic accuracy. Delayed culturing after storage at -80°C may not be reliable, in particular with regard to Gram-negative bacteria.

Serum bile acids in patients with hepatopulmonary syndrome

Backgroundu2002Hepatopulmonary syndrome (HPS) occurs in 20u200a-u200a30u200a% of patients with cirrhosis and is associated with increased mortality. Cholestasis and accumulation of bile acids (BAs) play a major role in chronic liver disease. Aimu2002We aimed to evaluate the clinical role of serum BAs in patients with HPS. Methodsu2002Seventy-four patients with cirrhosis were included in this prospective study. Marker for cholestasis as total and individual serum BAs, bilirubin, alkaline phosphatase (AP), and gamma-glutamyl transpeptidase (GGT) were analyzed in patients screened for HPS.u200aCriteria of HPS were fulfilled in 26 patients (35u200a%). Resultsu2002In contrast to AP and GGT, bilirubin and serum BAs were significantly elevated in patients with HPS (median total BAs in HPS 83.5 μmol/L, IQR 43.1u200a-u200a148.9 vs. no HPS 26.9 μmol/L, 11u200a-u200a75.6; pu200a<u200a0.001). Total BAs correlated with gas exchange by means of PaO2u200a/u200aAaPO2 (r: -0.28, pu200a<u200a0.05; r: 0.24, pu200a<u200a0.05) and portal pressure (r: 0.33, pu200a<u200a0.05). BAs were associated with HPS independently severity of underlying liver disease (OR: 1.012, 95u200a% CI:xa01.001u200a-u200a1.023, pu200a<u200a0.05). Conclusionu2002BA retention is associated with HPS and gas exchange abnormalities. Future studies should assess whether modulation of BAs signaling may impact the course of HPS.

Health-related quality of life of long-term survivors of intensive care: changes after intensive care treatment

SummaryObjectiveThe aim of the study was to determine if health-related quality of life of long-term survivors changes 24 months after intensive care treatment compared to the quality of life before admission.MethodsFrom 281 patients treated at the ICU in 2001, 132 survivors were contacted by phone on average 24 months after discharge. Fernandez questionnaire was used to assess preadmission quality of life prospectively and postdischarge quality of life, retrospectively. In addition, age, sex, admission diagnosis, ICU length of stay, presence of organ failure, and necessity of mechanical ventilation were determined.ResultsIn the 101 ICU survivors who responded to the questionnaire, the total score of quality of life did not change significantly over time (5.48u2009±u20095.3 before admission vs. 5.6u2009±u20095.8 at follow-up; pu2009=u20090.9). Similarly, the performance of normal daily activities did not alter (3.0u2009±u20093.5 vs. 3.39u2009±u20093.6; pu2009=u20090,3). In contrast, the ability to perform basic physiological activities worsened significantly (0.39u2009±u20090.76 vs. 0.76u2009±u20091.52; pu2009=u20090.037), whereas the emotional state improved significantly after intensive care treatment (2.08u2009±u20091.78 vs. 1.46u2009±u20091.56, pu2009=u20090.003). In a stepwise multiple regression analysis the total score of quality of life before admission was the only variable which influenced the quality of life 2 years after ICU-stay.ConclusionsIn the interviewed population the total score of health-related quality of life did not change after intensive care treatment. Surprisingly, emotional state improved significantly although physical performance decreased. Quality of life after ICU discharge was predominantly influenced by preadmission quality of life. However, these results are not reflective of all ICU survivors.ZusammenfassungZielAufgabe der vorliegenden Untersuchung war es, Verhealth-relader gesundheitsbezogenen Lebensqualität von Langzeitüberlebenden nach intensivmedizinischer Behandlung zu untersuchen.MethodikVon 281 an einer internistischen Intensivstation im Jahr 2001 behandelten Patienten wurden 132 Langzeitüberlebende an Hand des Fernandez Fragebogens bezüglich ihrer gesundheitsbezogenen Lebensqualität vor (retrospektiv) und 24xa0Monate nach (prospektiv) der kritischen Erkrankung telefonisch befragt. Zusätzlich wurden Alter, Geschlecht, Intensivstationsaufenthaltsdauer, Organversagen und Notwendigkeit einer künstlichen Beatmung erfasst.ErgebnisseBei den 101 Patienten, die die Fragen beantworteten, veränderte sich der Gesamtscore der Lebensqualität nicht signifikant (5,48u2009±u2009u20095,3 vor vs. 5,6u2009±u20095,8 2xa0Jahre nach kritischer Erkrankung; pu2009=u20090,9). Ähnlicherweise änderte sich das Ausüben normaler täglicher Aktivitäten nicht (3,0u2009u2009±u2009u20093,5 vs. 3,39u2009u2009±u20093,6; pu2009u2009=u2009u20090,305). Im Gegensatz dazu verschlechterten sich die physiologischen Grundaktivitäten signifikant (0,39u2009u2009±u2009u20090,76 vs. 0,76u2009u2009±u2009u20091,52; pu2009=u2009u20090,037), während sich der emotionale Status signifikant verbesserte (2,08u2009±u20091,78 vs. 1,46u2009±u20091,56, pu2009=u20090,003). In der multiplen Regressionsanalyse beeinflusste die Lebensqualität vor der akuten kritischen Erkrankung als einzige Variable signifikant die Lebensqualität beim 2-Jahres Follow-Up.SchlussfolgerungenDer Gesamtscore der gesundheitsbezogenen Lebensqualität änderte sich nicht 2 Jahre nach Therapie an einer internistischen Intensivstation. Überraschenderweise verbesserte sich der emotionale Status trotz Verschlechterung der körperlichen Funktionen. Die Lebensqualität der Langzeitüberlebenden wurde vorwiegend beeinflusst von der Lebensqualität bereits vor Auftreten der intensivpflichtigen Erkrankung. Naturgemäß kann von diesen Daten nicht generell auf alle Langzeitüberlebende von intensivpflichtigen Erkrankungen rückgeschlossen werden.

Health-related quality of life of long-term survivors of intensive care: changes after intensive care treatment. Experience of an Austrian intensive care unit.

SummaryObjectiveThe aim of the study was to determine if health-related quality of life of long-term survivors changes 24 months after intensive care treatment compared to the quality of life before admission.MethodsFrom 281 patients treated at the ICU in 2001, 132 survivors were contacted by phone on average 24 months after discharge. Fernandez questionnaire was used to assess preadmission quality of life prospectively and postdischarge quality of life, retrospectively. In addition, age, sex, admission diagnosis, ICU length of stay, presence of organ failure, and necessity of mechanical ventilation were determined.ResultsIn the 101 ICU survivors who responded to the questionnaire, the total score of quality of life did not change significantly over time (5.48u2009±u20095.3 before admission vs. 5.6u2009±u20095.8 at follow-up; pu2009=u20090.9). Similarly, the performance of normal daily activities did not alter (3.0u2009±u20093.5 vs. 3.39u2009±u20093.6; pu2009=u20090,3). In contrast, the ability to perform basic physiological activities worsened significantly (0.39u2009±u20090.76 vs. 0.76u2009±u20091.52; pu2009=u20090.037), whereas the emotional state improved significantly after intensive care treatment (2.08u2009±u20091.78 vs. 1.46u2009±u20091.56, pu2009=u20090.003). In a stepwise multiple regression analysis the total score of quality of life before admission was the only variable which influenced the quality of life 2 years after ICU-stay.ConclusionsIn the interviewed population the total score of health-related quality of life did not change after intensive care treatment. Surprisingly, emotional state improved significantly although physical performance decreased. Quality of life after ICU discharge was predominantly influenced by preadmission quality of life. However, these results are not reflective of all ICU survivors.ZusammenfassungZielAufgabe der vorliegenden Untersuchung war es, Verhealth-relader gesundheitsbezogenen Lebensqualität von Langzeitüberlebenden nach intensivmedizinischer Behandlung zu untersuchen.MethodikVon 281 an einer internistischen Intensivstation im Jahr 2001 behandelten Patienten wurden 132 Langzeitüberlebende an Hand des Fernandez Fragebogens bezüglich ihrer gesundheitsbezogenen Lebensqualität vor (retrospektiv) und 24xa0Monate nach (prospektiv) der kritischen Erkrankung telefonisch befragt. Zusätzlich wurden Alter, Geschlecht, Intensivstationsaufenthaltsdauer, Organversagen und Notwendigkeit einer künstlichen Beatmung erfasst.ErgebnisseBei den 101 Patienten, die die Fragen beantworteten, veränderte sich der Gesamtscore der Lebensqualität nicht signifikant (5,48u2009±u2009u20095,3 vor vs. 5,6u2009±u20095,8 2xa0Jahre nach kritischer Erkrankung; pu2009=u20090,9). Ähnlicherweise änderte sich das Ausüben normaler täglicher Aktivitäten nicht (3,0u2009u2009±u2009u20093,5 vs. 3,39u2009u2009±u20093,6; pu2009u2009=u2009u20090,305). Im Gegensatz dazu verschlechterten sich die physiologischen Grundaktivitäten signifikant (0,39u2009u2009±u2009u20090,76 vs. 0,76u2009u2009±u2009u20091,52; pu2009=u2009u20090,037), während sich der emotionale Status signifikant verbesserte (2,08u2009±u20091,78 vs. 1,46u2009±u20091,56, pu2009=u20090,003). In der multiplen Regressionsanalyse beeinflusste die Lebensqualität vor der akuten kritischen Erkrankung als einzige Variable signifikant die Lebensqualität beim 2-Jahres Follow-Up.SchlussfolgerungenDer Gesamtscore der gesundheitsbezogenen Lebensqualität änderte sich nicht 2 Jahre nach Therapie an einer internistischen Intensivstation. Überraschenderweise verbesserte sich der emotionale Status trotz Verschlechterung der körperlichen Funktionen. Die Lebensqualität der Langzeitüberlebenden wurde vorwiegend beeinflusst von der Lebensqualität bereits vor Auftreten der intensivpflichtigen Erkrankung. Naturgemäß kann von diesen Daten nicht generell auf alle Langzeitüberlebende von intensivpflichtigen Erkrankungen rückgeschlossen werden.

671 HEPATORENAL SYNDROME IN PATIENTS WITH HEPATOPULMONARY SYNDROME

Background and Aims: Hepatopulmonary syndrome (HPS) occurs in 20–30% of patients with cirrhosis. Patients with HPS have >2fold increased mortality. Contributing causes are unknown. There is lack data of concerning impairment of kidney function and hepatorenal syndrome (HRS) in patients with HPS. Methods: 203 patients with liver cirrhosis were screened for presence of HPS and HRS. HPS wsa defined according to consensus guidelines (1.) cirrhosis, 2.) AaDO2 >15mmHg, 3.) intrapulmonary vascular dilatation in contrast enhanced echocardiography). [1] HRS was defined according to established criteria. [2] Liver transplantation and survial was assessed during follow up. A p-value 1.5mg/dL. Underlying causes of renal impairment were HRS in 12 (33%), diabetic nephropathy in 6 (17%), hypovloemia in 8 (22%), glomerulanephritis in 3 (8%) and shock in 7 (19%) patients. HRS was the only cause of renal impairment that was significantly higher in HPS positive patients (7 (54%) versus 5 (22%), p < 0.05). Multivariate regression analysis revealed 2 risk factors for presence of HRS: refractory ascites (OR 33.4, p < 0.001) and presence of HPS (OR 4.9, p < 0.05). Discussion: HPS is an independent riask factor for presence of HRS. Patients with HRS should be screened for presence of HPS for early recognition and oxygen administration in case of severe gas exchange abnormality.