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Objective: Lung transplantation for pulmonary hypertension (PH) is usually performed on cardiopulmonary bypass, with the disadvantage of full systemic anticoagulation, uncontrolled allograft reperfusion and aggressive ventilation. These factors can be avoided with intra- and postoperatively prolonged extracorporeal membrane oxygenator (ECMO) support., Patients and Methods: Between February 1999 and March 2001, 17 consecutive patients with PH (systolic pulmonary artery pressure >70 mmHg) of different etiologies underwent bilateral lung transplantation (BLTX). There were 11 females and six males in the age range from 7 to 50 years (mean age, 28.4+/-12.9 years). Six patients were preoperatively hospitalized, four in the intensive care unit (ICU), one was on ECMO for 3 weeks pretransplantation, and one was resuscitated and bridged with ECMO for 1 week until transplantation. Femoral venoarterial ECMO support with heparin-coated circuits was set up after induction of anesthesia and discontinued at the end of surgery (n=3) or extended for 12 h median into the postoperative period (n=14). Postoperative ventilation pressure was kept below 25 mmHg. Allograft function at 2 h after discontinuation of ECMO, outcome and adverse events were monitored in all patients. Mean follow up time was 18+/-11.4 months., Results: The perioperative mortality was 5.9% (n=1). Arterial oxygen pressure measured 2 h after weaning from ECMO, and under standard mechanical ventilation with a peak pressure of 25 mmHg and inspired oxygen fraction of 0.4, was 157+/-28 mmHg. The mean pulmonary artery pressures were reduced to 29+/-3,4 from 66+/-15 mmHg before transplantation. Postoperative complications included rethoracotomy due to bleeding (n=4) and temporary left ventricular failure (n=4). Median ICU stay was 12 days. Incidence of rejection within the first 100 days was 0.4 per patient., Conclusion: BLTX with intraoperative and postoperatively prolonged ECMO support provides excellent initial organ function due to optimal controlled reperfusion and non-aggressive ventilation. This results in improved outcome even in advanced forms of PH.

Objectives: To evaluate the performance of the logistic organ dysfunction (LOD) system for the assessment of morbidity and mortality in multiple organ dysfunction/failure (MOD/F) in an independent database and to evaluate the use of sequential LOD measurements for the prediction of outcome., Design and Setting: Prospective, multicentric cohort study in 13 adult medical, surgical, and mixed intensive care units (ICUs) in Austria., Patients: A total of 2,893 consecutive admissions to the ICUs., Measurements and Main Results: Patient vital status at ICU and hospital discharge was recorded. Univariate analysis showed that the LOD was able to distinguish between survivors and nonsurvivors (2 vs. 6 median score). Within organ systems, higher levels of the severity of organ dysfunction were consistently associated with higher mortality. For the prediction of hospital mortality, the original prognostic LOD model did not perform well in our patients, as indicated by the goodness-of-fit C statistic. Using multiple logistic regression we developed a prognostic model with a satisfactory fit in our patients. The integration of further measurements during the ICU stay increased discrimination but not calibration., Conclusions: The LOD system is well correlated well with the numbers and levels of organ dysfunctions and discriminates well between survivors and nonsurvivors. It can thus be used to quantify the baseline severity of organ dysfunction. Moreover, after customization of the predictive equation the LOD predicted hospital mortality in our patients with high precision. It thus provides a combined measure of morbidity and mortality for critically ill patients with MOD/F.

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.

Background: Impaired pulmonary function is a frequent finding in patients undergoing orthotopic liver transplantation (OLT). Experimental data suggest an essential contribution of splanchnic ischemia and reperfusion as a result of intraoperative volume shifts, i.e., the accumulation of extravascular lung water (EVLW). Increases of intrathoracic blood volume (ITBV) and pulmonary blood volume (PBV) might additionally influence pulmonary capillary fluid filtration. The main objective of this study was to determine the intrathoracic volume changes during OLT and to test whether there were any relationships between intra- and extravascular volume shifts and pulmonary function, as determined by the calculation of venous admixture (QS/QT) and alveolar-arterial oxygen gradient (AaDO2)., Methods: Twenty-five patients undergoing OLT were studied. Using the transpulmonary double indicator dilution method, ITBV, PBV, and EVLW were determined from the mean transit times and exponential decay times of the indocyanine green and the thermal indicator curves recorded simultaneously with a fiberoptic catheter in the descending aorta. Recordings were made after induction of anesthesia, at the end of the anhepatic stage, immediately after reperfusion, and 1 and 4 h postoperatively., Results: Significant increases in QS/QT related to changes of ITBV were observed after reperfusion. Only a minor impact on AaDO2 was perceived. EVLW remained constant during the study period., Conclusions: Postreperfusion increases of ITBV influence pulmonary function, as demonstrated by the increase in QS/QT. However, they need not be associated with greater EVLW levels, and impact on oxygenation is less severe than assumed. Hence, sufficient mechanisms protecting oxygenation and stalling increased EVLW seem to be present during uncomplicated human OLT.

Background: Acute renal failure (ARF) can be triggered or aggravated by reactive oxygen species (ROS) but established ARF per se might also affect the antioxidant defence mechanisms of the organism. We evaluated a broad pattern of antioxidants in critically ill patients with multiple organ failure with (MOF-ARF) and without acute renal failure (MOF) to identify any potential involvement of renal dysfunction in the depletion of the antioxidant system., Methods: Observational study; 13 patients with MOF were investigated (9 with and 4 without ARF), and 17 healthy subjects served as controls. Blood samples were drawn after establishment of MOF. Plasma levels of ascorbate, alpha-tocopherol, retinol, beta-carotene, selenium and lipid peroxidation products (MDA) were determined and the activities of the antioxidant 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., Results: Plasma levels of ascorbate, beta-carotene and selenium were reduced in both patient groups, when compared to controls. Decrease in selenium was more pronounced in the MOF-ARF group. MDA levels were increased in both groups, again being more pronounced in MOF-ARF patients compared to MOF patients. Hydrogen peroxide production by neutrophils from both patient groups was lower than from controls., Conclusion: A depression of the antioxidative system is present in critically ill patients with MOF. In patients with associated ARF this was even more pronounced and plasma MDA levels were higher, suggesting an additional effect on the antioxidative potential in the presence of renal dysfunction and/or renal replacement therapy.

Objectives: To evaluate the ability of an interdisciplinary data set (recently defined by the Austrian Working Group for the Standardization of a Documentation System for Intensive Care [ASDI]) to assess intensive care units (ICUs) by means of the Simplified Acute Physiology Score II (SAPS II) for the severity of illness and the simplified Therapeutic Intervention Scoring System (TISS-28) for the level of provided care., Design: A prospective, multicentric study., Setting: Nine adult medical, surgical, and mixed ICUs in Austria., Patients: A total of 1234 patients consecutively admitted to the ICUs., Interventions: Collection of data for the ASDI data set., Measurements and Main Results: The overall mean SAPS II score was 33.1+/-2.1 points. SAPS II overestimated hospital mortality by predicting mortality of 22.2%+/-2.9%, whereas observed mortality was only 16.8%+/-2.2%. The Hosmer-Lemeshow goodness-of-fit test for SAPS II scores showed lacking uniformity of fit (H = 53.78, 8 degrees of freedom; p < .0001). TISS-28 scores were recorded on 8616 days (30.6+/-1.5 points). TISS-28 scores were higher in nonsurvivors than in survivors (30.4+/-0.9 vs. 25.7+/-0.4, respectively; p < .05). No significant correlation between mean TISS-28 per patient per unit on the day of admission and mean predicted hospital mortality (r2 = .23; p < .54) or standardized mortality ratio per unit (r2 = -.22; p < .56) was found., Conclusions: Implementation of an interdisciplinary data set for ICUs provided data with which to evaluate performance in terms of severity of illness and provided care. The SAPS II did not accurately predict outcomes in Austrian ICUs and must, therefore, be customized for this population. A combination of indicators for both severity of illness and amount of provided care is necessary to evaluate ICU performance. Further data acquisition is needed to customize the SAPS II and to validate the TISS-28.

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: 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.

Background: Mechanical hyperventilation is an established treatment to reduce brain edema and intracranial pressure in patients with encephalopathia caused by acute liver failure. Hyperventilation and ensuing hypocarbia may also affect central and systemic circulation and thereby influence graft performance in patients following orthotopic liver transplantation (OLT)., Methods: We measured the effects of normocapnia and hypocapnia on systemic hemodynamics, gastric tonometry, as a marker of splanchnic oxygenation, and the indocyanine green kinetic, as a global marker of graft function, in humans post OLT., Results: Hyperventilation was performed to a PaCO2 of 4.2 +/- 0.4 kPa (31 +/- 3.4 mm Hg) for about 1 h in 14 liver transplant recipients. Systemic hemodynamics as well as indices of splanchnic oxygenation and indocyanine green kinetics remained statistically unchanged., Conclusion: We did not observe any statistically significant circulatory effects or changes in indocyanine green kinetics in liver transplant recipients in the immediate OLT postoperative period caused by short-term mechanical hyperventilation.

Objective: Since the treatment of patients with severe ARDS using the extracorporal lung assist (ECLA) methods remains a cost intensive and speculative procedure, a knowledge based computer system should be created and evaluated in order to support clinical decisions., Methods: The model was based on the fuzzy set theory and therefore able to give decisions between yes and no, that means that a criterion could also be fulfilled to 35% or 80% for example. The development of this computer program consists of two steps: first, the entry criteria for the ECLA therapy were established within a framework of an international evaluation of clinical data from 3 centres (Berlin, Marburg, Vienna). Here, inherent vagueness, uncertainty of the occurrence and limited availability of medical data are to be considered to establish a useful tool. Secondly, this was done by grouping and weighting of parameters by the system and the status of each patient or patient group was assigned by the percentage of fulfillment of the criterion., Results: By using a mixed sample of patients from these three centres, the fulfillment of entry criteria according either to definitions of Berlin or to definition of Marburg was different (68% versus 36%). Other differences (36% vs. 22% and 68% vs. 60%) were found between the fuzzy based score and the crisp score which represents the usually performed method., Conclusions: This now preevaluated minimal data set to describe severe ARDS patients based on the fuzzy set theory may be useful to evaluate patients for ECLA therapy or for another controlled ARDS-therapy.

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 IIAM) (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.

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.

Objective: To evaluate the effects of pentoxifylline on hemodynamics and systemic oxygenation in septic and nonseptic critically ill patients., Design: Prospective clinical investigation., Setting: Intensive care unit (ICU) of a university hospital., Patients: Nineteen critically ill patients were included in the study 1 to 4 days after their admission to the ICU. A systemic inflammatory response syndrome was present in 12 patients, fulfilling at least two of the American College of Chest Physicians/ Society of Critical Care Medicine Consensus Conference criteria. The other seven patients did not fulfill these criteria and were classified as nonseptic., Interventions: All patients were mechanically ventilated. The dosage of catecholamines was kept constant during the entire study period and at least during 15 mins before the start of the study. In both study groups, pulmonary and radial artery catheters were inserted and 5 mg/kg of pentoxifylline (diluted in 300 mL of physiologic saline) was intravenously administered over a period of 180 mins at a rate of 100 mL/hr., Measurements and Main Results: Hemodynamic variables, oxygen transport (DO2), oxygen uptake (VO2), and oxygen extraction ratio were determined before pentoxifylline, after 2.5 mg/kg of pentoxifylline, after 5 mg/kg of pentoxifylline, and 60 mins after the termination of pentoxifylline. Repeated-measures analysis of variance and Mann-Whitney test were used for statistical analysis. At baseline, there were significant differences between the septic and the nonseptic groups in mean pulmonary arterial pressure (septic: 31 +/- 5 mm Hg; nonseptic: 26 +/- 7 mm Hg, p < .05), and pulmonary vascular resistance index (PVRI) (septic: 344 +/- 121 dyne.sec/ cm5.m2; nonseptic: 233 +/- 100 dyne.sec/cm5.m2, p < .05). In the septic group, significant increases in heart rate and cardiac index were observed. Systemic vascular resistance index and PVRI decreased. No significant changes in hemodynamic variables occurred in the nonseptic group. In both groups, DO2 and VO2 increased significantly, while oxygen extraction ratio remained unchanged., Conclusions: The administration of pentoxifylline to septic patients results in a significant improvement in hemodynamic performance compared with critically ill nonseptic patients. The better hemodynamic state is accompanied by an increase in DO2 and VO2 with unchanged oxygen extraction ratio.

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.

Objective: To determine possible changes in outcome from acute respiratory distress syndrome (ARDS) and to compare severity of lung injury and methods of treatment from 1967 to 1994., Data Sources: Computerized (Medline, Current Contents) and manual (Cumulated Index Medicus) literature search using the key word and/or title ARDS., Study Selection: Only clinical studies published as full papers reporting data on both patient mortality (survival) and oxygenation index (PaO2/FIO2) were included. Single case reports, abstracts, reviews and editorials were excluded from evaluation., Data Extraction: Relevant data were extracted in duplicate, followed by quality checks on approximately 80% of data extracted., Data Synthesis: 101 papers reporting on 3264 patients were included: 48 studies (2207 patients) were performed in the USA, 43 studies (742 patients) in Europe and 10 studies (315 patients) elsewhere. Mortality reported in these studies was 53 +/- 22% (mean +/- SD), with no apparent trend towards a higher survival (1994: 22 studies, mortality 51 +/- 19%). The mean PaO2/FIO2 ratio remained unchanged throughout the observation period (118 +/- 47 mmHg). No correlation could be established between outcome and PaO2/FIO2 or lung injury score. Patients who underwent pressure-limited ventilation had a significantly lower mortality (35 +/- 20%) than patients on volume-cycled ventilation (54 +/- 22%) or patients for whom there was no precise information on ventilatory support (59 +/- 19%). Significantly lower PaO2/FIO2 ratios (61 +/- 17 mmHg) were observed in patients prior to extracorporeal lung assist, together with mortality rates in the range of those for conventionally treated patients (55 +/- 22%)., Conclusions: The mortality of ARDS patients remained constant throughout the period studied. Therefore, the standard for outcome in ARDS should be a mortality in the 50% range. Neither PaO2/FIO2 ratio nor lung injury score was a reliable predictor for outcome in ARDS. Patients might benefit from pressure-limited ventilatory support, as well as extracorporeal lung assist. Since crucial data were missing in most clinical studies, thus preventing direct comparison, we emphasize the importance of using standardized definitions and study entry criteria.

Study Objective: To evaluate the percentage of nitric oxide (NO) responders in septic shock patients with ARDS. Additionally, to investigate long-term NO effects on cardiac performance and oxygen kinetic patterns in NO responders vs nonresponders., Design: Prospective cohort study., Setting: ICU of a university hospital., Patients: Twenty-five consecutive patients with a diagnosis of septic shock and established ARDS requiring inotropic and vasopressor support., Interventions: After diagnosis of ARDS, NO was administered at 18 or 36 ppm. Patients demonstrating a NO-induced rise of arterial oxygen tension of 20% or more and/or a fall in mean pulmonary artery pressure of 15% or more were grouped as NO responders; others were grouped as nonresponders., Measurements and Results: Ten patients (40%) were NO responders, while 15 patients (60%) were nonresponders. Mortality was 40% in NO responders and 67% in nonresponders (NS). NO responders developed a significantly lower mean pulmonary artery pressure (28 +/- 6 vs 33 +/- 6 mm Hg; p < 0.05), lower pulmonary vascular resistance (PVR: 258 +/- 73 vs 377 +/- 163 dyne.s.cm-5.m-2; p < 0.05), and higher PaO2/FIO2 ratio (192 +/- 85 vs 144 +/- 74 mm Hg; p < 0.05) within the study period. In responders, NO-induced afterload reduction resulted in increased right ventricular ejection fraction (RVEF: 40 +/- 7 vs 35 +/- 9%; p < 0.05), significantly higher cardiac index (CI: 4.5 +/- 1.1 vs 4.0 +/- 1.2 L.min-1.m-2; p < 0.05) and oxygen delivery (DO2: 681 +/- 141 vs 599 +/- 160 mL.min-1.m-2; p < 0.05) compared with nonresponders. In NO nonresponders, RVEF was correlated with PVR, CI, DO2, mixed venous oxygen saturation (SvO2), and oxygen extraction ratio (O2ER) (r = +/- 0.60 to +/- 0.69; p < 0.05). No significant correlation between RVEF and any of these parameters was observed in responders. SvO2 (75 +/- 7 vs 69 +/- 8%; p < 0.05) and O2ER (0.24 +/- 0.06 vs 0.27 +/- 0.06; p < 0.05) were significantly different between responders and nonresponders, while no difference in oxygen consumption was observed (161 +/- 41 vs 153 +/- 43 mL.min.m-2)., Conclusions: Inhaled NO is effective in only a subgroup of septic ARDS patients, with a higher, but insignificantly different percentage of survivors in the responder group. NO responders were characterized by increased RVEF accompanied by higher CI, DO2, and lower O2ER. In nonresponders, RVEF remained depressed, with a close correlation between RVEF and CO as well as DO2 and O2ER. Thus, nonresponders seem to suffer from impaired cardiac reserves and correspondingly lower oxygen transport variables.

The influence of pentoxifylline on human polymorphonuclear granulocyte (PMN) respiratory burst activity (RBA) was studied in 23 patients fulfilling the established criteria of sepsis and in 10 healthy donors. Pentoxifylline (PTX) was administered (5 mg/kg) by intravenous infusion in 13 septic patients over a period of 180 min. The control group consisted of 10 patients with septic syndrome who received an infusion of physiological saline. For determination of RBA, 10 mL of blood was drawn at respective time intervals before, during, and after treatment with PTX or a placebo. RBA measurements were performed using a chemiluminescence assay after stimulation of PMN with formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol-myristate-acetate, and opsonized zymosan, respectively. RBA measurements of each patient were performed in replicate samples. CL was measured for 1 h at respective time intervals (1, 3, 5, 8, 10, 15 min etc). RBA of PMN of septic patients was compared with RBA of PMN of healthy donors and patients receiving PTX were compared with controls. Our results demonstrate that PMN of patients with sepsis had an increased oxidative response compared with healthy donors. We found that PTX administered intravenously was able to reduce this reactivity. RBA was significantly decreased during PTX infusion when PMN were stimulated with FMLP and phorbol-myristate-acetate, compared with the control group. No significant decrease was observed when PMN were stimulated with opsonized zymosan. These data suggest that PTX may be a valuable drug in septic state.

Purpose: Evaluation of the effects of nimodipine administration during and after cardiopulmonary resuscitation (CPR) on oxygen delivery and consumption was the aim of this study., Methods: A randomized double-blind study in 32 anesthetized domestic pigs was performed. After 5 minutes of ventricular fibrillation (VF) and 5 minutes of external CPR, epinephrine (50 micrograms/kg) and either nimodipine or placebo (10 micrograms/kg bolus, 1 microgram/kg/min continuously throughout 4 hours of observation) were administered. One minute later (equal to 11 minutes VF), the first countershock was given. If this failed to restore spontaneous circulation, epinephrine and countershocks were repeated for a maximum of 30 minutes., Results: Eleven of 12 nimodipine- and 7 of 14 placebo-treated pigs could be resuscitated successfully and survived the observation period (P < .05). Hemodynamic responses to nimodipine were characterized by significant decreases in systemic vascular resistance and mean arterial pressure from 10 minutes after restoration of spontaneous circulation onwards with consequent significant increases in cardiac output. Median systemic oxygen delivery indices (DO2I) in nimodipine-treated pigs were significantly higher at all measuring points when compared with placebo-treated animals. Median systemic oxygen consumption indices (VO2I) did not differ significantly between groups. Median oxygen extraction ratios in nimodipine-treated pigs were in the same range as prearrest and were lower when compared with placebo-treated pigs (at 30 minutes P < .05 and at 120 minutes P < .01). DO2I and VO2I were poorly correlated in all pigs treated with nimodipine and in 3 of 7 animals treated with placebo, suggesting supply independency in these animals. This difference between groups was significant (P < .05)., Conclusions: Our findings suggest that in nimodipine-treated animals, a lower oxygen deficit or a better redistribution of regional blood flow occurred after circulatory arrest and resuscitation.

Endothelin-1 (ET-1), a potent vasoconstrictor peptide produced by endothelial cells and degraded predominantly in the pulmonary vasculature, has been implicated in the development of various organ dysfunctions. To determine the pathophysiologic role of ET-1 in adult respiratory distress syndrome (ARDS) and the impact of impaired lung function on transpulmonary peptide handling, we compared plasma levels and pulmonary ET-1 balance in 14 patients with ARDS and in seven healthy control subjects. To obtain comparable conditions in both groups, the ET-1 level was raised in the control group by exogenous infusion (0.4 pmol/kg/min) to 9.4 +/- 0.8 pmol/L. ARDS was accompanied by a hyperdynamic circulatory pattern with increased cardiac output and depressed total vascular resistance but, simultaneously, pulmonary hypertension. Venous ET-1 concentration was massively increased in ARDS (9.8 +/- 1.2 versus 2.1 +/- 0.2 pmol/L, p < 0.001). In control subjects, the lung cleared the major fraction of ET-1 (fractional extraction 43 +/- 8.8%, uptake 12.5 +/- 2.5 pmol/min). In contrast, in ARDS there was a pronounced pulmonary releases into the circulation (32.8 +/- 10.3 pmol/min). We conclude that ET-1 concentrations are elevated in ARDS as the result of both increased formation and decreased disposal. Lung failure affects not only gas exchange but also nonrespiratory, metabolic pulmonary functions.

Study Objective: To investigate the frequency and extent of spontaneous changes ("events") in continuously measured mixed venous oxygen saturation (SvO2) in septic patients and to determine whether attention to individual event-frequency offers additional information for patient management., Design: Nonrandomized prospective study., Setting: General intensive care unit at a university hospital., Patients: Fifteen patients suffering from septic shock and multiple organ dysfunction syndrome., Measurements: For the continuous assessment of SvO2 a fiberoptic pulmonary artery catheter (Baxter Edwards) was inserted in all patients. A certain event was defined as a sudden change in SvO2 of > or = 5 percent lasting for > 10 min. All events were grouped as either moderate (< or = 10 percent changes in SvO2) or severe events (> 10 percent changes). Hemodynamics and inotropic support, oxygenation and ventilatory support, hemoglobin levels and body temperature were determined at the event and compared with the ultimate values registered before the event., Results: We evaluated 377 events during an observation period of 1,575 h. Patients' mean SvO2 levels ranged between 72 +/- 7 and 82 +/- 4. Desaturations below 65 percent (39 out of 377 events) occurred in 11 patients. Overall, 74 percent of all events were moderate and 26 percent were severe. The incidence of events was 5.6 +/- 1.5 during 24 h in survivors (n = 10) and 6.3 +/- 1.6 during 24 h in nonsurvivors (n = 5). While in survivors only 20 percent of all events were severe events, this portion was significantly higher in nonsurvivors (34 percent; p = 0.03). In 67 percent of all events we observed changes in the registered physiologic parameters or therapeutic interventions probably causing the event. The cause of the remaining 33 percent of all events could not be elucidated., Conclusions: The SvO2 of septic shock patients is mainly normal or even supranormal. However, short-term changes in SvO2 do occur frequently in these patients. Nonsurvivors exhibit a higher frequency as well as a significantly greater severity of events, which may point toward a concealed mismatch of oxygen supply and demand. A high incidence of short-term SvO2 changes in a septic shock patient may be of diagnostic and prognostic significance. Therefore, we recommend the installation of a computerized alarm-function for the automatic detection and indication of frequent events.

The relationship between oxygen consumption (VO2) and oxygen delivery (DO2) is of interest in critically ill patients. Various studies of these parameters have resulted in different concepts for optimizing DO2 and VO2. During liver transplantation without anhepatic veno-venous bypass, caval cross-clamping initiates a series of haemodynamic and metabolic alterations including the rapid change from hyperdynamic to hypodynamic conditions. In addition, simultaneous changes in DO2 and VO2 occur in these patients. The goal of our present study was to test the clinical relevance of therapeutic interventions based on metabolic monitoring in patients with terminal liver disease undergoing orthotopic liver transplantation. PATIENTS AND METHODS. One hundred sixty-two consecutive patients were evaluated. According to outcome, patients were divided into survivors (n = 115, group A), nonsurvivors (n = 30, group B), and patients with primary nonfunction of the liver graft (n = 17, group C). One hundred twenty patients were cirrhotics due to either alcohol (n = 36), aggressive hepatitis (n = 30), or biliary cirrhosis (n = 54); 42 had a neoplastic disease. Haemodynamic measurements, data for calculations of DO2 and VO2, and blood samples for arterial and mixed-venous blood gases and subsequent laboratory analysis were taken during the surgical procedure at six timepoints: after induction of anaesthesia (I); during preparation of the recipient liver, before cross-clamping (II); 10 min after clamping of the inferior vena cava (III); 10 min before unclamping (IV); with all vessels open, 10 min after declamping during reperfusion (V); and 60 min after declamping (VI). Anaesthesia was induced with thiopentone (3-5 mg/kg i.v.) and fentanyl (15 micrograms/kg min i.v.). Muscle relaxation was achieved with pancuronium (0.1 mg/kg i.v.). Anaesthesia was maintained with i.v. supplements of fentanyl (5-10 micrograms/kg) and pancuronium (4 mg) as required. Volume-cycled ventilation was established with a mixture of O2 in air with a positive end-expiratory pressure of 5 mm H2O to keep the PaO2 above 100 mm Hg and the PaCO2 around 35 mm Hg (Servo 900 C-Ventilator, Siemens). To maintain body temperature, all patients were positioned on a heating blanket set at 38 degrees C. The inspired gases were warmed and humidified using a dual servo-heated humidifier. Mannitol (20-40 g i.v.) or sorbitol (16-24 g i.v.) was given to prevent renal dysfunction during the cross-clamping procedure. Lactated Ringer's solution and fresh frozen plasma administration was guided by cardiovascular performance and requirements for clotting factors, respectively. Cardiac output was measured by the thermodilution method using a pulmonary artery catheter. Blood lactate, haemoglobin concentration, arterial and mixed-venous oxygen content, and oxygen saturation were measured (Hemoxymeter OSM3). VO2 and DO2 were calculated according to standard formulas. STATISTICAL ANALYSIS. The data from groups A, B, and C were compared using a multivariate analysis of variance with Tukey's method for multiple comparisons. A least-square regression was used to correlate metabolic data. RESULTS. The perioperative course of the determinants of oxygen transport is shown in Table 1. After cross-clamping, the cardiac index (CI) decreased in groups A (47%), B (53%), and C (51%) and increased to pre-anhepatic levels after reperfusion of the new liver. This was associated with distinct decreases in DO2 (A: 42%, B: 47%, and C: 45%) and VO2 (A: 8%, B: 19%, C: 25%). After reperfusion of the new allograft (V), VO2 increased in groups A (24%) and B (18%) as compared to controls (I). By contrast, in group C, a distinct further decrease in VO2 (13%) was detected. In these patients, there was a significantly greater increase in mixed-venous saturation accompanied by a further decrease in body temperature. As shown in Figures 1 and 2, no significant relationship was found between O2 transport, VO2, and blood lactate. DISC