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Byline: W. Plochl (1), C. G. Krenn (1), H. Pokorny (2), L. Pezawas (3), T. Pezawas (1), H. Steltzer (1) Keywords: Key words Tirilazad mesylate; Liver transplantation; Malonaldehyde; Ischaemia-reperfusion injury Abstract: Objectives: To test the hypothesis whether in patients undergoing liver transplantation the antioxidant tirilazad mesylate can reduce hepatic ischaemia-reperfusion injury and improve postoperative outcome. Design: Prospective, randomised, placebo controlled trial. Setting: University hospital. Patients: 20 patients were randomised to receive either tirilazad mesylate or placebo (saline). Interventions: Patients in the tirilazad group (n = 10) received four intravenous infusions of tirilazad at 6-h intervals (men 3 mg/kg, women 3.75 mg/kg) after the induction of anaesthesia. The other patients (n = 10) served as controls. Measurements and results: Plasma levels of malonaldehyde (MDA) were determined after the induction of anaesthesia prior to the infusion of tirilazad (baseline), during the anhepatic period, and 5 min and 24 h after reperfusion. Postoperatively, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and serum cholinesterase were determined daily for 1 week. Compared to baseline, plasma MDA levels did not significantly change during the anhepatic period and after reperfusion and they did not differ between groups. Postoperative liver enzymes and prothrombin time did not differ between groups, but on the first (p = 0.03) and second (p = 0.01) postoperative day cholinesterase levels were significantly higher in tirilazad-treated patients than in control patients. For neither length of stay in the intensive care unit nor hospital stay were any differences observed between groups. Conclusions: In patients undergoing liver transplantation, tirilazad does not improve overall outcome. Whether the higher cholinesterase levels on the first 2 postoperative days in tirilazad treated patients indicates an earlier recovery of liver function remains to be tested. Author Affiliation: (1) Department of Anaesthesiology and General Intensive Care, University of Vienna, Vienna, Austria, AT (2) Department of Surgery, University of Vienna, Vienna, Austria, AT (3) Department of General Psychiatry, University of Vienna, Vienna, Austria, AT Article note: Received: 13 November 1998 Final revision received: 10 March 1999 Accepted: 6 April 1999

Byline: P. G. H. Metnitz (1), A. Valentin (2), H. Vesely (3), C. Alberti (4), T. Lang (5), K. Lenz (6), H. Steltzer (1), M. Hiesmayr (1) Keywords: Key words Severity of illness; Outcome; Customization; Mortality prediction; Uniformity; of fit; SAPS II Abstract: Objectives: To evaluate the prognostic performance of the original Simplified Acute Physiology Score (SAPS) II in Austrian intensive care patients and to evaluate the impact of customization. Design: Analysis of the database of a multicenter study. Setting: Nine adult medical, surgical, and mixed intensive care units (ICUs) in Austria. Patients: A total of 1733 patients consecutively admitted to the ICUs. Measurements and results: The database included admission data, SAPS II, length of stay, and hospital mortality. The Hosmer--Lemeshow goodness-of-fit test for the SAPS II showed a lack of uniformity of fit (H = 89.1, 10 df, p < 0.0001 C = 91.8, 10 df, p < 0.0001). Subgroup analysis showed good performance in patients with cardiovascular (medical and surgical) diseases as the primary reasons for admission. A new predictive equation was derived by means of the logistic regression. Goodness-of-fit was excellent for the customized model (SAPS II.sub.AM) (H = 11.2, 9 df, p = 0.33, C = 11.6, 9 df, p = 0.24). The mean standardized mortality ratio (SMR) changed from 0.81 +- 0.26 to 0.93 +- 0.29 with customization. Conclusions: SAPS II was not well calibrated when applied to all patients. However, it performed well for patients with cardiovascular diseases as the primary reason for admission and may thus be applied to these patients. Standardized mortality ratios that are calculated from scoring systems without known calibration must be viewed with skepticism. Author Affiliation: (1) Department of Anesthesiology and General Intensive Care, University Hospital of Vienna, Austria, AT (2) Department of Internal Medicine II, KA Rudolfstiftung, Vienna, Austria, AT (3) Department of Anesthesiology and General Intensive Care, Hanusch KH, Vienna, Austria, AT (4) Department of Intensive Care Medicine, Saint-Louis Hospital, Paris, France, FR (5) Department of Medical Statistics, University of Vienna, Austria, AT (6) Department Internal Medicine, KH Barmherzige Brueder, Linz, Austria, AT Article note: Received: 11 May 1998 Final revision received: 20 August 1998 Accepted: 12 October 1998

Byline: P. G. H. Metnitz (1), C. Bartens (1), M. Fischer (2), P. Fridrich (1), H. Steltzer (1), W. Druml (2) Keywords: Key words ARDS; Antioxidants; Vitamins; Selenium; Acute lung injury Abstract: Objectives: Reactive oxygen species (ROS) have been implicated in the pathophysiology of ARDS. We investigated the pattern of antioxidants in plasma and ROS production by neutrophils in patients with ARDS over 6 days. Design: Observational study. Blood samples were taken when the diagnosis was made (D0) and after 3 (D3) and 6 days (D6) during therapy. Setting: Intensive care units at a University Hospital. Patients: Eight patients with ARDS were investigated, 17 healthy volunteers served as controls. Measurements and results: Plasma levels of ascorbate, [alpha]-tocopherol, retinol, [beta]-carotene, selenium and lipid peroxidation products (MDA) were determined and the activities of the antioxidative enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione-peroxidase (GSH-PX) in erythrocytes were measured. In addition, ROS production (superoxide anion and hydrogen peroxide) in activated neutrophils was assessed. Plasma levels of [alpha]-tocopherol, ascorbate, [beta]-carotene and selenium were reduced from the onset of illness. MDA plasma levels were increased throughout the illness. ROS generation from neutrophils was normal on D0 and decreased to D6 in ARDS patients. Conclusion: The antioxidative system is severely compromised in patients with ARDS. Plasma levels of [alpha]-tocopherol, ascorbate, [beta]-carotene and selenium are decreased. Elevated MDA levels provide further evidence of massive oxidative stress. The routine replacement of micronutrients according to recommended daily allowances was inadequate to compensate for the increased requirements. Author Affiliation: (1) Dept. of Anesthesia and General Intensive Care, Vienna General Hospital, University of Vienna, Waehringer Gurtel 18--20, A-1090 Vienna, Austria, AT (2) Dept. of Internal Medicine III, University of Vienna, Vienna General Hospital, Waehringer Guertel 18--20, A-1090 Vienna, Austria email: wilfred. druml@akh-wien.ac.at Tel. + 43 1 40 400 4503 Fax + 43 1 40 400 4543, AT Article note: Received: 8 April 1998 Final revision received: 22 September 1998 Accepted: 5 October 1998

Byline: K. Reinhart (1), P. Radermacher (2), C. L. Sprung (3), D. Phelan (4), J. Bakker (5), H. Steltzer (6) Author Affiliation: (1) Friedrich-Schiller-Universitat, Klinik fur Anasthesiologie und Intensivtherapie, Bachstrasse 18, D-07743 Jena, Germany FAX: +49 (36 41) 63 32 56, DE (2) Sektion Anasthesiologische Pathophysiologie und Verfahrensentwicklung, Universitatsklinik fur Anasthesiologie, Klinikum der Universitat, Parkstrasse 11, D-89073 Ulm (3) Hadassah Hebrew University, Medical Center, P. O. Box 12000, 91120 Jerusalem, Israel, IL (4) Department of Anaesthesia and Intensive Care, University College Dublin, National University of Ireland, Mater Misericordiae Hospital, Eccles St., Dublin 7, Ireland, IE (5) Ziekenhuis Centrum, Lokatie Lukas, Postbus 9014, 7300 DS Apeldoon, Niederlande, NL (6) Klinik fur Anaesthesie u. Allgemeine Intensivmedizin, Wahringer Gurtel 18--20, A-1090 Wien, Osterreich Article note: Received: 11 December 1996 Accepted: 17 March 1997

Byline: H. Steltzer (1), P. Krafft (1) Author Affiliation: (1) Dept. of Anesthesiology and General Intensive Care, University of Vienna, Waehringer Guertel 18--20, A-1090 Vienna, Austria e-mail: peter.krafft@akh-wien.ac.at Tel.: + 43-1-40400 4118 Fax: + 43-1-40400 6882, AT Article note: Accepted: 1 July 1999

Byline: H. Steltzer (1), P. Krafft (1) Author Affiliation: (1) Department of Anesthesiology and Intensive Care Medicine, University of Vienna, Waehringer Guertel 18--20, A-1090 Vienna, Austria FAX: +43 (1) 4 04 00 68 82 e-mail: heinz.steltzer@akh-wien.ac.at, AT Article note: Received: 4 July 1997 Accepted: 7 July 1997

Byline: F. Kapadia (1), K. Reinhart (2), P. Radermacher (2), C. L. Sprung (2), D. Phelan (2), J. Bakker (2), H. Steltzer (2) Author Affiliation: (1) Hinduja National Hospital & Medical Research Center, Veer Savarkar Marg, 400016, Mahim Mumbai, India (2) Department of Anesthesiology and CCM, Hadassah Hebrew University Medical Center, P.O. Box 12000, 91120, Jerusalem, Israel Article History: Registration Date: 24/03/2009 Received Date: 10/07/1997 Accepted Date: 24/09/1997

Byline: H. Steltzer (1) Author Affiliation: (1) Department of Anaesthesia & General Intensive Care, University of Vienna, Waehringer Guertel 18--20, A-1090 Vienna, Austria e-mail: Heinz.Steltzer@akh-wien.ac.at Tel.: + 43-1-4 04 00 41 18 Fax: + 43-1-4 04 00 68 82, AT Article note: Accepted: 2 March 2000

Byline: K. Reinhart (1), P. Radermacher (1), C. L. Sprung (1), D. Phelan (1), J. Bakker (1), H. Steltzer (1) Author Affiliation: (1) Department of Anesthesiology and CCM, Hadassah Hebrew University Medical Center, P. O. Box 12 000, 91120 Jerusalem, Israel, IL Article note: Received: 22 September 1997 Accepted: 24 September 1997

Background: Although accurate assessment of liver function in liver transplant recipients is of crucial importance for optimal timing of the procedure and for determining graft viability, none of the many available methods has proven reliable in the clinical routine. Thus, a novel non-isotopic assay of tyrosine kinetics using the tyrosine-containing dipeptide L-alanyl-L-tyrosine (Ala-Tyr) was tested for its clinical feasibility in patients undergoing orthotopic liver transplantation (OLT)., Methods: Plasma levels of tyrosine and clearance of tyrosine released after infusion of the dipetide Ala-Tyr were assessed before and one day after OLT in 10 liver transplant recipients with normal graft function, also in three organ donors and in three recipients showing poor graft function. Standard laboratory parameters (e.g. aminotransferases) and the plasma disappearance rate of indocyanine green were also measured., Results: Following uneventful OLT, tyrosine plasma levels (before 127 +/- 15 micromol/vs. post-OLT 52 +/- 6 micromol/l, P < 0.05) and kinetics (tyrosine clearance: before 206 +/- 77 ml/min vs. post-OLT 371 +/- 109 ml/min, P < 0.05) were normalized. In cases of severe graft dysfunction, tyrosine kinetics (tyrosine clearance: 238 +/- 61 ml/min) resembled the situation in end-stage liver disease, whereas no such correlation was seen with conventional markers of liver function. Organ preservation had only a minor impact on tyrosine kinetics (n.s.)., Conclusion: OLT rapidly normalizes both the plasma levels and the kinetics of tyrosine. Graft failure is associated with an immediate rise in plasma tyrosine levels and a delay in tyrosine elimination. Our results show that tyrosine clearance using the dipetide Ala-Tyr is a suitable non-isotopic, non-invasive indicator of graft viability in the early postoperative course following OLT.

Acute liver failure (ALF) is a rare clinical syndrome associated with a mortality of up to 80% and its management remains an interdisciplinary challenge. Despite recent improvements in intensive care management, the mortality of patients with ALF remains high and is related to complications such as cerebral edema, sepsis and multiple organ failure. Emergency orthotopic liver transplantation (OLT) is currently the only effective treatment for those patients who are unlikely to recover spontaneously. Nevertheless, OLT is not always possible because of the shortage of the organs and/or complications related to ALF. Newly introduced liver-assist devices can temporarily support the patient's liver until native liver recovers or can serve as a bridging device until a liver graft is available. The support devices use both cell-based and non-cell-based techniques. One of the latest non-cell-based extracorporeal hepatic support devices, the molecular adsorbent recycling system (MARS), is based on the concept of albumin dialysis. MARS utilises selective hemodiafiltration with countercurrent albumin dialysis aiming to selectively remove both water-soluble and albumin-bound toxins of the low and middle molecular-weight range. We report on a young patient who presented with clinical symptoms of ischemic hepatitis and multi-organ failure (APACHE II score 38-->predicted postoperative mortality 87%) due to prolonged hemorrhagic shock. OLT was contraindicated because of history of pancreas cancer with metastases. It was necessary to use aggressive conservative therapy and an extracorporeal liver-assist device until liver regeneration began and hemodynamic conditions were stable. The patient underwent five treatments with MARS. During the treatment, there were improvements of hemodynamics, respiratory function, acid-base disturbances and laboratory parameters. The plasma disappearance rate of indocyanine green, a parameter of dynamic liver function, improved during MARS treatment. Although repeated neurological examination predicted diffuse brain damage (brain oedema, decreased cerebral blood flow), the patient recovered without any neurological deficits. The patient survived and was discharged from the hospital in good condition. In this case MARS treatment was successful in supporting the patient through the most critical period of ALF.

Background and Aim of Study: Pre-emptive analgesia represents a treatment strategy which tries to prevent the development of pain by inhibiting central reactions to peripheral sensory stimuli. In a prospective randomized double-blind placebo-controlled study, the effect of oral premedication with 4 mg of a slow-release hydromorphone preparation on postoperative piritramide consumption and subjective pain perception is being evaluated., Patients and Methods: 96 women undergoing hysterectomy were randomly assigned to four study groups. Patients from groups 1 and 2 received hydromorphone and placebo respectively two hours before surgery, while those from groups 3 and 4 were given the same substances one hour after the end of the operation. Postoperative pain relief was provided by a patient-controlled infusion pump with piritramide. The intensity of postoperative pain as perceived by the patients was quantified on a visual analogue scale. Piritramide consumption and pain scores were recorded at 1 and 24 hours after surgery. Approval of the local Ethics Committee had been obtained beforehand as well as written informed consent from the patients., Results: No significant differences in piritramide consumption were observed in between the four study groups. Visual analogue scale (VAS) ratings at 1 and 24 hours after surgery did not show any significant differences either--irrespective of whether the patients had received hydromorphone or placebo preoperatively or postoperatively., Conclusion: In our study, oral administration of 4 mg of slow-release hydromorphone did not show any greater pre-emptive analgesic effect than placebo.

Tonometry is a clinically accepted method to monitor blood flow of the splanchnic region, which is of particular interest in orthotopic liver transplantation (OLT). We investigated the hemodynamic changes and the tonometrically registered perioperative course of the difference between gastric mucosal pCO2 (prCO2) and arterial mucosal CO2 (CO2 gap) in 23 patients undergoing OLT without veno-venous bypass. Gastric mucosal pH (pHi) was additionally calculated. Despite significant changes in systemic hemodynamics during the anhepatic stage and after reperfusion and a significant drop in pHi during anhepacy, the difference between prCO2 and CO2 was constant. These contrasting findings of tonometry, i.e. solely a drop in pHi is, in our opinion, a consequence of the poor metabolic capacity of the liver in the perioperative OLT period, which influenced the calculation of the pHi with the Henderson-Hasselbalch equation. We conclude that, due to methodical problems, calculated pHi is not a reliable indicator of splanchnic blood flow and oxygenation during OLT. We therefore suggest that the prCO2 and the CO2 gap be used to monitor the splanchnic region. These parameters, obtained perioperatively, do not indicate a further reduction in splanchnic oxygenation despite profound changes in systemic hemodynamics during OLT without veno-venous bypass.

Objectives: A comparison of data from different intensive care units (ICUs) needs standardized documentation. In this study the ASDI documentation standard for intensive care was tested in clinical practice. Goal of the study was to evaluate parameters and functionality required for a national, interdisciplinary documentation system for intensive care., Design: 13 ICUs participated in a 4-week trial using the provided program for documentation of all admitted patients during the observation period. In addition, a questionnaire was distributed to the unit coordinators., Results: 376 patients were documented in 1591 patient days. Valid SAPS II scores were found in only 29% of the discharged patients (39.1 +/- 15.5 points). Time needed for data entry exceeded preset limits (ten minutes per patient and day) in 38% of the cases. All participants affirmed the necessity of a documentation standard for intensive care, giving quality control and cost analysis as the most important reasons., Conclusion: The ASDI data set fitted existing needs very closely. Only 7 out of 122 parameters (5.7%) were found to be superfluous and thus removed. Measures to reduce documentation effort to the default limits were a) a new, date orientated concept for manual recording, b) rede-sign of the user interface with new, user friendly data entry possibilities, and c) the integration of statistical analysis and reports in the documentation system. The revised data set represents a broad-based consensus, which seems to be well-suited as foundation for the national quality assurance program.