[Hemoadsorption for blood purification-incomparability of clinically available procedures]. / Hämoadsorption zur Blutreinigung ­ Unvergleichbarkeit der klinisch angebotenen Verfahren.

BACKGROUND: In the field of intensive care medicine, but also increasingly in cardiac surgery, the use of adsorptive blood purification technologies for the treatment of hyperinflammatory conditions is becoming progressively more important. In addition to the CytoSorb concept, which is more and more clinically accepted and currently the most frequently used method, other companies-particularly from China-have recently entered the market with similar concepts. OBJECTIVES: Given this, the aim of this article is to analyze the different aspects of the various hemoadsorption products offered on the market today and to take a critical look at the available evidence. METHODS: Technical features, application-specific characteristics, and the existing evidence of the adsorption technologies CytoSorb® (CytoSorbentsTM Inc., Monmouth Junction, NJ, USA), Jafron® HA series (Jafron Biomedical Co., Guangdong, China), and Biosky® MG series (Biosun® Medical Technology Co., Foshan City, Guangdong Province, China) were analyzed. The purely substance-specific methods for endotoxin elimination only (Toraymyxin®, Alteco®) were not considered. RESULTS: A comprehensive analysis of these criteria reveals that there are considerable differences between the various available technologies in terms of materials used, adsorption characteristics, application, and available data on safety and clinical experience. Furthermore, it becomes clear that not only the efficacy of blood purification technologies should be considered in terms of an effect-price-performance ratio, but that in particular the safety of the individual technologies is of crucial importance. DISCUSSION: Among the technologies analyzed, CytoSorb currently represents the most investigated and clinically established procedure. Furthermore, it should be noted that clinical results, but particularly safety-relevant aspects, are not transferable between the products due to technically different procedures.

Intrathoracic fluid volumes and pulmonary function during orthotopic liver transplantation.

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.

In vivo modulation of human neutrophil function by pentoxifylline in patients with septic syndrome.

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.

Mixed venous oxygen saturation in critically ill septic shock patients. The role of defined events.

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.

Effectiveness of nitric oxide inhalation in septic ARDS.

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 use of the antioxidant tirilazad mesylate in human liver transplantation: is there a therapeutic benefit?

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.

Evaluation of the logistic organ dysfunction system for the assessment of organ dysfunction and mortality in critically ill patients.

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.

Antioxidant status in patients with acute respiratory distress syndrome.

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.

The acute respiratory distress syndrome: definitions, severity and clinical outcome. An analysis of 101 clinical investigations.

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.

Prognostic performance and customization of the SAPS II: results of a multicenter Austrian study. Simplified Acute Physiology Score.

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.

Oxygen kinetics during liver transplantation: the relationship between delivery and consumption.

In anesthetized humans, oxygen consumption is independent of oxygen delivery above a critical threshold. Below this critical level, lactic acid is a marker of anaerobic metabolism and tissue oxygen debt, and heralds a supply dependency of oxygen consumption. The goal of this study was to determine whether a threshold value for oxygen delivery below which oxygen consumption becomes supply dependent can be identified in patients with normal, impaired, or absent liver function. Measurements were made in 34 surviving patients (group 1) and in 16 nonsurvivors with sepsis and postoperative liver graft failure (group 2). Hemodynamic measurements and blood samples were taken 10 minutes after introduction of anesthesia, 10 minutes after cross-clamping, and 10 minutes after reperfusion of the new liver. At these time points, we measured blood lactate, cardiac output, and arterial and mixed venous oxygen contents in order to calculate oxygen consumption and oxygen delivery. In both groups, cardiac output, oxygen delivery, and oxygen consumption decreased during the anhepatic phase and increased after unclamping of the inferior vena cava. Lactate increased in both groups during surgery, but was significantly higher in nonsurvivors (6.6 +/- 0.4 mmol/L) than in survivors (4.6 +/- 0.1 mmol/L) (P < .05). With similar changes for oxygen delivery and oxygen consumption during increased lactate levels we could not identify a clear supply dependency of oxygen consumption in survivors and nonsurvivors during liver transplantation. We conclude that the interpretation of blood lactate levels during circulatory shock can be biased due to a reduced lactate clearance in patients with impaired liver function, unrelated to the status of the relationship between oxygen delivery and consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Nimodipine after circulatory arrest: effects on oxygen delivery and consumption.

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.

Bilateral lung transplantation via two sequential anterolateral thoracotomies.

OBJECTIVE: Bilateral anterior trans-sternal thoracotomy (clam shell incision) is the standard approach used for bilateral sequential lung transplantation (BLTX). The morbidity of this large incision can be considerable. Two separate sequential anterolateral thoractomies represent a less invasive approach. METHODS: The value of this approach was investigated in a prospective series of 22 consecutive patients who received BLTX between June 1997 and July 1998. Their underlying diseases were COPD (n = 16), cystic fibrosis (n = 4) and other (n = 2). All patients underwent BLTX through two anterolateral thoracotomies, without the use of cardiopulmonary bypass. The anterior mediastinum and the sternum with all the surrounding tissue were left completely intact. Twenty-one patients underwent spirometrical examination during the postoperative in-hospital stay. Follow-up is 7+/-4 months (range: 3 to 15). RESULTS: The only intraoperative complication was severe reperfusion edema of the first transplanted lung seen in one patient at the end of the operation, which required pneumonectomy during the same session. All other operations were uneventful. The difference between the cold ischemic time of the first and second transplanted lung was 83+/-17 min. Median intubation duration, ICU- and in-hospital-stay were 1.5, 5 and 20 days, respectively (ranges: 1 to 96, 2 to 96 and 15 to 96, respectively). One major perioperative complication occurred and was due to gross donor/recipient size mismatch: the patient required lobectomy of the consolidated right upper lobe 11 days after transplantation. In 19 patients (86.4%), this less extensive incision allowed early postoperative mobilization, which resulted in good ventilatory performance, with VC of 53+/-15 and FEV1 of 60+/-20% of the predicted, respectively, at the first spirometry, 3 weeks after the operation. Three months survival was 100%. CONCLUSION: The bilateral sequential anterolateral thoracotomy represents a safe and minimal invasive approach for BLTX compared with the clam shell incision. It minimizes the operative trauma, improves postoperative functional recovery and prevents the potential spread of unilateral complications to the other pleural cavity.

Perioperative cytokines during orthotopic liver transplantation without venovenous bypass.

UNLABELLED: Since most of studies investigating cytokine levels during human orthotopic liver transplantation used venovenous bypass (VVB), it may be difficult to distinguish between the increase in proinflammatory mediators induced by VVB, by ischemia-reperfusion injury or by splanchnic venous congestion in the anhepatic phase. The goal of this investigation was to assess the levels of interleukin-6 (IL-6) and soluble interleukin-2 receptors (sIL-2r) during OLT procedures routinely performed without VVB. PATIENTS AND METHODS: Twenty-one consecutive patients underwent OLT with cross clamping of the inferior caval vein without VVB. Soluble IL-2r concentrations were measured by means of luminescence enzyme immunometric assay and IL-6 by means of a sequential immunometric assay. Time points (TP) of sampling were before induction of anesthesia (TP1), after cross-clamping of the inferior vena cava (TP2), 15 minutes after reperfusion (TP3), and 24 hours after the transplant procedure (TP4). RESULTS: Soluble IL-2r increased significantly 24 hours after transplantation (P =.02) compared to TP1, TP2, and TP3. IL-6 increased significantly during the anhepatic period (TP2 vs TP1, P =.003) and again in the reperfusion period (TP2 vs TP3, P =.002). Twenty-four hours after surgery IL-6 declined significantly (TP3 vs TP4, P =.001), but remained significantly higher (P = 0.04) compared to TP1. Furthermore, we examined the relative changes (DeltaTP %) in perioperative levels of cytokines compared with those previously published in studies using VVB. We observed higher values of DeltaTP % of IL-6 in TP2 and TP4 among our group of patient without VVB. The data on sIL-2r were similar, suggesting no major effects of the operative technique on sIL-2r levels. CONCLUSION: The two interleukins showed different perioperative trends. Our data suggest that cross clamping contributes more to cell activation, namely, increased release of IL-6 in the anhepatic phase than the use of VVB. However, no major differences were observed during the reperfusion period. The extent of clinical effect on graft function of higher IL-6 levels in the anhepatic period among recipients not supported with VVB remains to be clarified.

Perioperative kinetics of heat shock protein 60 in serum during orthotopic liver transplantation.

INTRODUCTION: Heat shock proteins (HSP) play essential roles in the synthesis, transport, and folding of proteins. During ischemia/reperfusion (I/R) injury to orthotopic liver transplants (OLT), disassembly of oligomeric complexes and unfolding of proteins are likely to occur, producing a major burden on HSP to prevent and/or reverse these events. To date, all studies have evaluated HSP expression in tissues after an I/R injury. No data are available on HSP serum levels during I/R injury in liver graft recipients. PATIENTS AND METHODS: We evaluated the intraoperative and perioperative kinetics of HSP60 in the serum of 25 liver graft recipients. RESULTS: We observed a significant increase in serum levels of HSP60 at 4 hours compared with 30 minutes after reperfusion of the graft (P = .028). The perioperative HSP60 kinetics in serum neither correlated with the cold ischemia time nor the indocyanin green clearance. The type of preservation solution had no effect on serum HSP60 levels. CONCLUSION: This first study provides evidence for increased serum levels of HSP60 after reperfusion in OLT. The perioperative kinetics of HSP60 in serum may result from suppressed protein synthesis caused by a reduced energy charge of hepatocytes during early reperfusion, impaired transcription, and/or corticosteroid treatment. Further studies are needed to clarify the role of HSP60 under clinical conditions including immunosuppressive medications in human OLT.

Severity and outcome of ARDS: the present place of extracorporeal lung assist (ECLA).

Within the last decade extracorporeal lung assist has been recommended for the treatment of acute respiratory distress syndrome. However, this recommendation was challenged by several recent clinical studies and reviews. The goal of our analysis was therefore to investigate data on outcome and severity of gas exchange disturbance published from patients treated with ECLA. These data were compared to a historical control group consisting of ARDS patients treated conventionally. Computerized (MEDLINE 1967-95) literature search using the keywords ARDS, ECLA, ECMO, ECCO2R and HUMAN was performed. Only clinical studies published as full papers reporting data on both, patients mortality and oxygenation index (PaO2/FiO2) were included. Overall mean mortality reported was 53 +/- 22% in 17 studies (419 patients), with no apparent trend towards a higher survival within the last decade with a mean PaO2/FIO2 (14 papers; 61 +/- 17 mmHg). However, mean mortality rates of ARDS patients requiring ECLA was 52.3% and 44.9% if patients undergoing ECMO were excluded (3 papers). Therefore the mortality of these patients with severe lung injury was in the range of patients treated conventionally. Patient outcome observed in our analysis is in accordance with the mortality rates from the European ECLA centres published recently (49% in 1993). Therefore, we conclude that the mean mortality rate of patients suffering from severe ARDS treated with ECLA is in the 50% range and does not differ significantly from those of patients treated conventionally, despite significantly poorer pulmonary function.

Haemodynamic evaluation during small volume resuscitation in patients with acute respiratory failure.

In addition to the invasive haemodynamic monitoring procedures, an on-line assessment of cardiac performance by means of transoesophageal echocardiography might have a certain role in small volume resuscitation of patients with acute respiratory failure or Adult Respiratory Distress Syndrome (ARDS). The goal of this investigation was therefore to determine the effects of a hypertonic hyperoncotic solution, hypertonic hydoxyethl-starch (HHES), (HHES = HES [200.000/0.6-0.66; 60 g l-1; Leopold, Graz; Austria] combined with NaCl [75 g l-1) on haemodynamics and cardiac performance using the transoesophageal echocardiography. After institutional approval we investigated 23 patients suffering from septic ARDS after trauma or major surgery during four periods of resuscitation. Phase I = control values after infusion of 20 ml kg-1 crystalloid solution, phase II = 50% hypertonic hydroxyethyl-starch solution (2 ml kg-1), phase III = at the end of HHES (4 ml kg-1), IV = 30 min after the end of HHES. Before HHES-infusion, all patients showed arterial hypotension with mean arterial pressures of 64 +/- 2 mmHg. The infusion of 2 ml kg-1 HHES resulted in a significant increase of systemic and pulmonary arterial pressures over the study period. A significant improvement in cardiac output was associated with increasing stroke volumes, oxygen delivery and oxygen consumption (see Tables 1 and 2). Small volume resuscitation also resulted in significant increases of endsystolic and endiastolic left ventricular areas and the corresponding calculated wall stress (Figs 1-3). We conclude from our preliminary data that when using HHES, only modest fluid resuscitation was sufficient to restore adequate preload and oxygen delivery in patients with sepsis-related acute respiratory failure.

Effect of pre-emptive hydromorphone administration on postoperative pain relief--a randomized controlled trial.

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.

[Difference between gastric mucosal pCO2 and arterio-intramucosal pCO2 during orthotopic liver transplantation]. / Magenmukosa-pCO2 und arterio-intramukosale pCO2-Differenz während orthotoper Lebertransplantation.

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.

[Definition and evaluation of a documentation standard for intensive care medicine: the ASDI(Working Group for Standardization of a documentation system for Intensive care medicine) pilot project]. / Definition und Evaluation eines Dokumentationsstandards für Intensivmedizin: Das ASDI-Pilotprojekt.

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.