[Workflow management in the operating room. Analysis of potentials for optimizing efficiency at a university hospital]. / Ablauforganisation im Operationssaal : Analyse der Optimierungspotenziale an einem Universitätsklinikum.

BACKGROUND: The introduction of the diagnosis-related groups reimbursement system has increased cost pressures. Due to the interaction of many different professional groups, analysis and optimization of internal coordination and scheduling in the operating room (OR) is mandatory. The aim of this study was to analyze the processes at a university hospital in order to optimize strategies by identifying potential weak points. METHODS: Over a period 6 weeks before and 4 weeks after intervention processes time intervals in the OR of a tertiary care hospital (university hospital) were documented in a structured data collection sheet. RESULTS: The main reason for lack of efficiency of labor was underused OR utilization. Multifactorial reasons, particularly in the management of perioperative interfaces, led to vacant ORs. A significant deficit was in the use of OR capacity at the end of the daily OR schedule. After harmonization of working hours of different staff groups and implementation of several other changes an increase in efficiency could be verified. CONCLUSIONS: These results indicate that optimization of perioperative processes considerably contribute to the success of OR organization. Additionally, the implementation of standard operating procedures and a generally accepted OR statute are mandatory. In this way an efficient OR management can contribute to the economic success of a hospital.

[Importance of material logistics in the interface management of operation departments: is the supply of sterile equipment a new business area of operation room organization?]. / Bedeutung der Materiallogistik im Schnittstellenmanagement der Operationsabteilungen: Ist die Sterilgutversorgung ein neues Geschäftsfeld der OP-Organisation?

The implementation of diagnosis-related groups (DRGs) sharply increased economic pressure on hospitals. Hence, process optimization was focussed on cost-intensive areas, namely the operation room (OR) departments. Work-flow in the OR is characterized by a mandatory interlocking of the job functions of many different occupational groups and the availability of a variety of different materials. Alternatives for staff assignment optimization have been published in numerous publications dealing with the importance of OR management. In this connection the issue of material logistics in the context of OR management has not been frequently addressed. In order to perform a surgical procedure according to plan, one depends on personnel and on timely availability of the materials needed. Supply of sterilized materials is of utmost importance, because in most hospitals sterilized surgical devices constitute a critical resource. In order to coordinate the OR process with the production flow of sterilized materials, an organizational connection to the OR management makes sense. Hence, in a German university hospital the Department of Hospital Sterile Supplies was integrated into the OR management of the Department of Anesthesiology. This led to a close coordination of work-flow processes, and concomitantly a significant reduction of production costs of sterile supplies could be achieved by direct interaction with the OR. Thus, hospital sterile supplies can reasonably be integrated into an OR management representing a new interesting business area for OR organization.

Endothelin-1 in subarachnoid hemorrhage: An acute-phase reactant produced by cerebrospinal fluid leukocytes.

BACKGROUND AND PURPOSE: The most potent vasoconstrictor known, endothelin-1, is currently considered to mediate cerebral vasospasm in subarachnoid hemorrhage (SAH), which can cause delayed cerebral ischemia. In our study, we performed clinical and in vitro experiments to investigate the origin and the mechanisms of the secretion of endothelin-1 in SAH. METHODS: Endothelin-1 and markers of inflammatory host response (interleukin [IL]-1ss, IL-6, and tumor necrosis factor-alpha) were comparatively quantified in the cerebrospinal fluid (CSF) of SAH patients and control subjects, and concentrations were related to clinical characteristics. Furthermore, mononuclear leukocytes isolated from the CSF of SAH patients and control subjects were analyzed regarding their mRNA expression of endothelin-1 and inflammatory cytokines. Finally, complementary in vitro experiments were performed to investigate whether coincubation of blood and CSF can trigger leukocytic mRNA expression and release of these factors. RESULTS: Activated mononuclear leukocytes in the CSF of SAH patients synthesize and release endothelin-1 in parallel with known acute-phase reactants (IL-1ss, IL-6, and tumor necrosis factor-alpha). Complementary in vitro experiments not only further confirmed this leukocytic origin of endothelin-1 but also showed that aging and subsequent hemolysis of blood is sufficient to induce such endothelin-1 production. CONCLUSIONS: The demonstration that endothelin-1 is produced by activated CSF mononuclear leukocytes suggests that subarachnoid inflammation may represent a therapeutic target to prevent vasospasm and delayed cerebral ischemia after SAH.

Lipid mediators in inflammatory disorders.

During the past few decades, intensive collaborative research in the fields of chronic and acute inflammatory disorders has resulted in a better understanding of the pathophysiology and diagnosis of these diseases. Modern therapeutic approaches are still not satisfactory and shock, sepsis and multiple organ failure remain the great challenge in intensive care medicine. However, the treatment of inflammatory diseases like rheumatoid arthritis, ulcerative colitis or psoriasis also represents an unresolved problem. Many factors contribute to the complex course of inflammatory reactions. Microbiological, immunological and toxic agents can initiate the inflammatory response by activating a variety of humoral and cellular mediators. In the early phase of inflammation, excessive amounts of interleukins and lipid-mediators are released and play a crucial role in the pathogenesis of organ dysfunction. Arachidonic acid (AA), the mother substance of the pro-inflammatory eicosanoids, is released from membrane phospholipids in the course of inflammatory activation and is metabolised to prostaglandins and leukotrienes. Various strategies have been evaluated to control the excessive production of lipid mediators on different levels of biochemical pathways, such as inhibition of phospholipase A2, the trigger enzyme for release of AA, blockade of cyclooxygenase and lipoxygenase pathways and the development of receptor antagonists against platelet activating factor and leukotrienes. Some of these agents exert protective effects in different inflammatory disorders such as septic organ failure, rheumatoid arthritis or asthma, whereas others fail to do so. Encouraging results have been obtained by dietary supplementation with long chain omega-3 fatty acids like eicosapentaenoic acid (EPA). In states of inflammation, EPA is released to compete with AA for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivatives.

Role of NO and endothelin in hemoglobin-induced pulmonary vasoconstriction.

UNLABELLED: The underlying mechanisms of hemoglobin (Hb)-induced vasoconstriction are not yet well understood. The aim of this study was to elucidate the influence of nitric oxide (NO) and endothelin (ET) on Hb-induced pulmonary vasoconstriction. Therefore, an autologous Hb preparation was administered into isolated rabbit lungs, in which pulmonary artery pressure (PAP) and weight gain was monitored. Either glyceroltrinitrate (GTN; 10(-5) M; n=6), L-arginine (10(-2) M; n=6), L-NAME (10(-4)M; n=6), ET(A)- or ET(B)-receptor antagonists (BQ,23, 10 6M, n=6) or (BQ788, 10(-6) M, n=6) were added to the perfusion fluid and NOx and thromboxane A2 levels were measured. RESULTS: In the control group the Hb-stimulation resulted in a pressure response up to 25.1+/-2.1 mmHg (p < .05), which was 136+/-6% of the reference value. The PAP increase was significantly (p < .05) blunted after GTN (71+/-5%), L-arginine (93+/-6%) and BQ788 (88+/-7%). Pretreatment with L-NAME (139+/-13%) or BQ123 (115+/-9%) did not show significant changes in PAP. CONCLUSION: The reduction of the Hb-induced pulmonary hypertension by NO-donors points toward the inactivation of NO by free hemoglobin. Likewise, ET(B)-receptor mediated vasoconstrictive effects without changes in NOx concentrations seem to play a pathogenetic role in the Hb-induced pulmonary vasoconstriction.

Kupffer cells and neutrophils as paracrine regulators of the heme oxygenase-1 gene in hepatocytes after hemorrhagic shock.

Heme oxygenase (HO) plays a pivotal role for the maintenance of liver blood flow and hepatocellular integrity after hemorrhagic shock. We investigated the role of Kupffer cells and neutrophils as paracrine modulators of hepatocellular HO-1 gene expression in a rat model of hemorrhage and resuscitation. Male Sprague-Dawley rats (n = 6-10/group) were anesthetized (pentobarbital, 50 mg/kg intraperitonal) and subjected to hemorrhagic shock (mean arterial blood pressure: 35 mmHg for 60 min) or a sham protocol. Based on the time course of HO-1 gene expression, the effect of various antioxidants, Kupffer cell blockade [gadolinium chloride (GdCl3); 10 mg/kg; 24 h prior to hemorrhage or dichloromethylene diphosphonate (Cl2MDP); 1 mg/kg; 2 days prior to hemorrhage], or neutrophil depletion (vinblastine, 0.5 mg/kg, 5 days prior to hemorrhage) on induction of the HO-1 gene was assessed at 5 h of resuscitation, i.e., the time point of maximal induction. Kupffer cell blockade and antioxidants abolished HO-1 mRNA and protein induction after hemorrhage, while neutrophil depletion failed to affect hepatocellular HO-1 gene expression. In addition, Kupffer cell blockade aggravated hepatocellular injury. N-formyl-methionine-leucyl-phenylalanin (fMLP) induced a substantial influx of neutrophils into the liver but failed to induce hepatocellular HO-1 mRNA expression. These data suggest that Kupffer cells but not neutrophils induce an adaptive hepatocellular stress response after hemorrhage and resuscitation. Oxygen-free radicals released by Kupffer cells may serve as paracrine regulators of a hepatocellular stress gene which is necessary to maintain liver blood flow and integrity under stress conditions.

The role of endothelin-1 as a mediator of the pressure response after air embolism in blood perfused lungs.

OBJECTIVE: It is well known that lung embolism is associated with an increase in pulmonary vascular resistance. Since the mechanisms of pulmonary vascular reactions during embolism are still unclear, the aim of this study was to investigate the potential involvement of endothelin-1 (ET-1) and thromboxane A2 (TXA2) as mediators of the pulmonary artery pressure (PAP) increase after embolism using the selective ETA receptor antagonist LU135252 [1], the ETB receptor antagonist BQ788 [2], and the cyclooxygenase inhibitor diclofenac. DESIGN: Prospective experimental study in rabbits. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: 36 adult rabbits of either sex. INTERVENTIONS: The experiments were performed in 36 isolated and ventilated rabbit lungs which were perfused with a buffer solution containing 10% of autologous blood. Embolism was induced by the injection of 0.75 ml air into the pulmonary artery. MEASUREMENTS AND RESULTS: PAP and lung weight, reflecting edema formation, were continuously recorded. Perfusate samples were drawn intermittently to determine TXA2 and ET-1 concentrations. Air injection resulted in an immediate increase in PAP up to 22.8 +/- 1.4 mm Hg at 2.5 min (control, n = 6), which was parallelled by an enhanced generation of TXA2. No relevant edema formation occurred during the observation period. Pretreatment with the ETA receptor antagonist LU135252 significantly reduced the pressure reaction after air embolism (p < 0.001) whereas the ETB receptor antagonist BQ788 (n = 6) was without marked effects. The administration of diclofenac (n = 6) did not alter the PAP increase 2.5 min after embolism, but significantly reduced the pressure reaction during the further observation period (p < 0.001). The application of LU135252 and diclofenac together (n = 6) also significantly reduced the PAP increase from 2.5 min during the total observation period (p < 0.001). CONCLUSIONS: The acute pressure reaction after air embolism is mainly mediated via ET-1 by an ETA receptor related mechanism. TXA2 seems to maintain this reaction for a longer time.

ET-1-induced pulmonary vasoconstriction shifts from ET(A)- to ET(B)-receptor-mediated reaction after preconstriction.

Endothelin-1 (ET-1) has been reported to induce pulmonary vasoconstriction via either ET(A) or ET(B) receptors, and vasorelaxation after ET-1 injection has been observed. Our study investigated the effects of ET-1 in isolated rabbit lungs, which were studied at basal tone (part I) and after preconstriction (U-46619; part II). Pulmonary arterial pressure (PAP) and lung weight gain were monitored continuously. In part I, ET-1 (10(-8) M; n = 6; control) was injected after pretreatment with the ET(A)-receptor antagonist BQ-123 (10(-6) M; n = 6) or the ET(B)-receptor antagonist BQ-788 (10(-6) M; n = 6). The same protocol was carried out in part II after elevation of pulmonary vascular tone. ET-1 induced an immediate PAP increase (DeltaPAP 4.3 +/- 0.4 mmHg at 10 min) that was attenuated by pretreatment with BQ-123 (P < 0.05 at 10 min and P < 0.01 thereafter) and that was more pronounced after BQ-788 (P < 0.01 at 10 min and P < 0.001 thereafter). In part II, ET-1 induced an immediate rise in PAP with a maximum after 5 min (DeltaPAP 6.3 +/- 1.4 mmHg), leveling off at DeltaPAP 3.2 +/- 0.2 mmHg after 15 min. Pretreatment with BQ-123 failed to attenuate the increase. BQ-788 significantly reduced the peak pressure at 5 min (0.75 +/- 0.4 mmHg; P < 0.001) as well as the plateau pressure thereafter (P < 0.01). We conclude that ET-1 administration causes pulmonary vasoconstriction independent of basal vascular tone, and, at normal vascular tone, the vasoconstriction seems to be mediated via ET(A) receptors. BQ-788 treatment resulted in even more pronounced vasoconstriction. After pulmonary preconstriction, ET(A) antagonism exerted no effects on PAP, whereas ET(B) antagonism blocked the PAP increase. Therefore, ET-1-induced pulmonary vasoconstriction is shifted from an ET(A)-related to an ET(B)-mediated mechanism after pulmonary vascular preconstriction.

Generating a learning curve for pediatric caudal epidural blocks: an empirical evaluation of technical skills in novice and experienced anesthetists.

BACKGROUND AND OBJECTIVES: Learning curves for anesthesia procedures in adult patients have been determined, but no data are available on procedures in pediatric anesthesia. The aim of this study was to assess the number of caudal blocks needed to guarantee a high success rate in performing caudal epidural analgesia in children. METHODS: At a teaching hospital, the technical skills of 7 residents in anesthesiology who performed caudal blocks were evaluated during 4 months using a standardized self-evaluation questionnaire. At the start of the study period, the residents had no prior experience in pediatric anesthesia or in performing caudal epidural blocks. All residents entered the pediatric rotation after a minimum of 1 year of training in adult general and regional anesthesia. The blocks were rated using a binary score. For comparison, the success rates of 8 experienced staff anesthesiologists were collected during the same period using the same self-evaluation questionnaire. Statistical analyses were performed by generating individual and institutional learning curves using the pooled data. The learning curves were calculated with the aid of a least-square fit model and 95% confidence intervals were estimated by a Monte Carlo procedure with a bootstrap technique. RESULTS: The success rate of residents was 80% after 32 procedures (95% confidence interval of 0.59 to 1.00). The pooled success rate of the staff anesthesiologists was 0.73 (mean) with a standard deviation of 0.45, which was not statistically different from the success rate of the residents. CONCLUSION: High success rates in performing caudal anesthesia in pediatric patients can be acquired after a limited number of cases. Success rates of residents learning this procedure are comparable to the results of staff anesthesiologists.

Autotransfusion during extracorporeal membrane oxygenation.

To reduce allogeneic blood transfusion requirements during extracorporeal membrane oxygenation (ECMO) we evaluated an autotransfusion device which processes and retransfuses erythrocytes of changed ECMO-systems. We studied 10 elective changes of ECMO-systems in 7 patients. Hemoglobin levels, the amount of retransfused autologous blood and of transfused allogeneic packed red blood cell units were documented within 48 h after the system change and compared to the measurements obtained from former ECMO-system changes without using any autotransfusion device. We determined the Horrowitz-index, Interleukin 6, 10, TNF-alpha and endothelin-I concentrations and coagulation parameters during the 48 hours after system change to study the compatibility of this procedure. Allogeneic blood transfusion was reduced from 7 to 2 units of packed red cells using the autotransfusion device. Additionally, no hints of any harmful side effects in these patients was observed.

Adenosine A1 and A2 receptor agonists reduce endotoxin-induced cellular energy depletion and oedema formation in the lung.

BACKGROUND AND OBJECTIVE: Tissue depletion of adenosine during endotoxaemia has previously been described in the lung. Therapeutic approaches to prevent adenosine depletion and the role of A1 and A2 receptor agonists, however, have not been investigated until now. METHODS: In isolated and ventilated rabbit lungs, it was tested whether pretreatment with adenosine A1 agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 10(-7) mol, n = 6) or A2 receptor agonist 5'-(N-cyclopropyl)-carboxyamido adenosine (CPCA; 10(-7) mol, n = 6) prior to injection of lipopolysaccharide (LPS) (500 pg mL-1) influenced pulmonary artery pressure (PAP), pulmonary energy content and oedema formation as compared with controls, solely infused with LPS (n = 6). Release rates of adenosine and uric acid were determined by high-performance liquid chromatography. Pulmonary tissue concentrations of high-energy phosphates were measured and the adenine nucleotide pool, adenosine 5'-triphosphate (ATP)/adenosine 5'-diphosphate (ADP) ratio and adenylate energy charge of the pulmonary tissue were calculated. RESULTS: Administration of LPS induced increases in PAP within 2 h up to 20.8 +/- 2.9 mmHg (P < 0.01). While pretreatment with the A1 agonist merely decelerated pressure increase (13.8 +/- 1.1 mmHg, P < 0.05), the A2 agonist completely suppressed the pulmonary pressure reaction (9.6 +/- 1.0 mmHg, P < 0.01). Emergence of lung oedema after exclusive injection of LPS up to 12.0 +/- 2.9 g was absent after A1 (0.6 +/- 0.5 g) and A2 (-0.3 +/- 0.2 g) agonists. These observations were paralleled by increased adenosine release rates compared with LPS controls (P < 0.05). Moreover, tissue concentrations of ADP, ATP, guanosine 5'-diphosphate, guanosine 5'-triphosphate, nicotinamide-adenine-dinucleotide and creatine phosphate were significantly reduced after LPS. Consequently, the calculated tissue adenine nucleotide pool and the adenylate energy charge increased after adenosine receptor stimulation (P = 0.001). CONCLUSIONS: Adenosine A1- and A2-receptor agonists reduced LPS-induced vasoconstriction and oedema formation by maintenance of tissue energy content. Thus, adenosine receptor stimulation, in particular of the A2 receptor, might be beneficial during acute lung injury.

The ProSeal laryngeal mask airway and the laryngeal tube Suction for ventilation in gynaecological patients undergoing laparoscopic surgery.

BACKGROUND AND OBJECTIVE: ProSeal Laryngeal Mask Airway (PLMA) and Laryngeal Tube Suction (LTS), supraglottic airway devices allowing gastric drainage, were compared in this prospective, randomized study for airway management under conditions with elevated intra-abdominal pressure induced by capnoperitoneum. METHODS: Fifty patients undergoing elective gynaecological laparoscopic surgery were randomized to two groups of 25 each. After induction of general anaesthesia, devices were inserted, correct placement was verified, airway leak pressure was measured, and a gastric tube was inserted. Ease of insertion, quality of airway seal, risk of gastric insufflation and patient comfort were investigated. RESULTS: There were no differences in patient characteristics data for both groups. First-time insertion success rates were comparable for both groups: 92%--first attempt, 8%--second attempt for PLMA and LTS. Time until delivery of the first tidal volume for PLMA and LTS was 23.2 +/- 6.1 and 23.5 +/- 6.6s, airway leak pressure was 45.4 +/- 4.9 cmH2O and 45.6 +/- 6.7 cmH2O with cuff pressures adjusted to 60 cmH2O. No gastric insufflation, gas loss or signs of regurgitation were detected. Placement of a gastric tube was successful in all patients. Patients were questioned for sore throat and dysphagia after removal of devices. Sore throat was stated in 1%/0% (PLMA) and 8%/4% (LTS) after 6/24 h, dysphagia in 4%/4% (PLMA) and 12%/4% (LTS). CONCLUSIONS: Both devices provide a secure airway even under conditions of elevated intra-abdominal pressure. In this pilot study, no differences concerning handling or quality of airway seal were detected between PLMA and LTS.

Clonidine increases membrane-associated phospholipase A 2.

BACKGROUND AND OBJECTIVE: An anti-inflammatory effect of alpha2-adrenoreceptor agonists has been suggested. Phospholipase A2 is a key enzyme in the production of precursors of inflammatory lipid mediators. The aim of the present study was to investigate the effect of clonidine on phospholipase A2 activity in an established in vitro model. METHODS: Human being platelet membranes containing active phospholipase A2 were exposed to buffer control or to three increasing concentrations of clonidine. Phospholipase A2 was measured by a radioisotope technique. RESULTS: A massive increase in phospholipase A2 activity was measured after clonidine exposure leading to final values of 92.5 +/- 3.1 pmol mg protein(-1) min(-1) (4.5-fold higher than control values; P < or = 0.01 vs. control). After clonidine exposure the maximal reaction velocity increased, while the Michaelis-Menten constant did not change. The Lineweaver-Burk representation suggested an interaction of clonidine with the phospholipase A2-substrate complex as well as the phospholipase A2 molecule. CONCLUSION: We conclude that the putative anti-inflammatory effect of clonidine was not caused by inhibition of phospholipase A2.

[The significance of endothelin for physiologic and pathophysiologic processes of the lung]. / Die Bedeutung von Endothelin für physiologische und pathophysiologische Prozesse der Lunge.

The endothelins (ETs) are a family of three vasoactive peptides (ET-1, ET-2, ET-3) that were first described in 1988. ETs have a wide range of action including vasoconstriction, vasodilatation, bronchoconstriction, and mitogenesis. Two types of ET receptors, classified as ETA and ETB receptors, have been identified in gene technology. Endothelins are produced by endothelial cells, smooth muscle cells, and bronchial epithelial cells. Their vasoactive effects contribute not only to homoeostasis but ETs seem also to be involved in several pulmonary diseases. Elevated ET plasma levels have been found in patients suffering from asthma, pulmonary fibrosis, pulmonary hypertension, and acute lung injury. This review gives a short summary of the actual facts in endothelin research, focussing on the effects of ET-1 in pulmonary circulation.

[The effect of endothelin on granulocyte-endothelium interaction]. / Bedeutung von Endothelin bei der Granulozyten-Endothel-Interaktion.

PURPOSE: The interaction of activated granulocytes and endothelial cells influences not only capillary permeability but also increases pulmonary vascular resistance. The aim of this study was to evaluate the role of endothelin-1 (ET-1) during the granulocyte-mediated increase in pulmonary pressure. METHODS: The experiments were performed on isolated and ventilated rabbit lungs perfused with a blood-free buffer solution. Isolated, washed human granulocytes were injected into the pulmonary artery and stimulated by 10(-6) M N-formyl-L-leucin-methionyl-L-phenylalanine (FMLP). Pulmonary arterial pressure (PAP) was continuously registered, and perfusate samples were taken to determine ET-1 and eicosanoid levels. To analyse the role of ET-1, six lung preparations were pretreated with the ETA receptor antagonist BQ123 (10(-6) M) prior to FMLP injection. To analyse the role of thromboxane A2, six additional lung preparations were pretreated with the cyclooxygenase inhibitor diclofenac (10 micrograms/ml). Additionally, granulocytes were stimulated in vitro with FMLP for 15 min, and ET-1 concentration was measured in the supernatant. RESULTS: Immediately after FMLP injection, PAP increased to 18.5 +/- 1.6 mmHg, descending to values 4.8 +/- 0.8 mmHg above the baseline after 15 min. At this time, ET-1 could be detected in the perfusate. The concentrations of the cyclooxygenase products thromboxane A2 and prostacyclin remained nearly unchanged during the observation period. Pretreatment with the ETA receptor antagonist BQ123 significantly reduced the pressure response after FMLP injection (p < 0.01 at 5 and 10 min; p < 0.05 at 15 and 30 min). Pretreatment with the cycloocygenase inhibitor diclofenac failed to inhibit the pressure reaction evoked by activated granulocytes. In contrast to this, ET-1 was not detected after in vitro stimulation of granulocytes. CONCLUSION: ET-1 is involved as a mediator of pulmonary vasoconstriction due to granulocyte activation. Since in vitro FMLP-stimulation of human granulocytes did not induce ET-1 production, it seems likely that isolated activated granulocytes would not produce ET-1, but provoke the endothelial cells to release ET-1 in the pulmonary circulation.

In vitro effects of different medium molecular hydroxyethyl starch solutions and lactated Ringer's solution on coagulation using SONOCLOT.

UNLABELLED: Hydroxyethyl starch (HES) solutions are widely used to replace intravascular volume. HES solutions differ from each other with regard to molecular weight and mode of hydroxyl substitution (degree of hydroxylation, C2:C6 hydroxyethyl ratio, concentration), factors which may have varying effects on coagulation. We studied, in vitro, three different HES preparations (molecular weight/degree of hydroxylation/concentration/C2:C6 ratio of substitution 70.000/0. 5/6%/3.2; Pharmacia & Upjohn Co., Erlangen, Germany; 130.000/0. 4/6%/11.2 and 200.000/0.5/6%/4.6; Fresenius Co., Bad Homburg, Germany) and, for comparison, lactated Ringer's solution (RL) at 33% and 66% dilution with whole blood. The influence of hemodilution was measured by using routine laboratory variables and SONOCLOT (Sonoclot II Coagulation and Platelet Function Analyzer, Sienco Co.) analysis, using a viscoelastic test, on the cellular as well as on the plasmatic hemostatic system. For statistical analysis of quantitative data, we used nonparametric analysis of variance and adequate post hoc tests. Qualitative data were analyzed by using the nonparametric Kruskal-Wallis test. A P value below 0.05 was considered significant. In contrast to the control group with RL, the liquid phase of coagulation (activated clotting time) was slightly affected by the 33% diluted HES solutions. HES 70.000, 130. 000, and 200.000 interfered significantly with the early stage of coagulation as expressed by the clot rate (gel/fibrin formation). Clot maturation and speed of maturation (time to peak) were strongly affected by HES 70.000 at all grades of dilution. HES 130.000 showed a faster clot formation process compared with the other HES solutions. HES 130.000 diluted 33% showed a better clot retraction as compared with the other HES solutions. In conclusion, in vitro hemodilution comparing different medium molecular weight HES solutions reveals that HES 130.000 seems preferable regarding some aspects of clot formation and retraction. RL affected clot formation only minimally, except for the early activation of clotting, which was measured by a shortened activated clotting time. IMPLICATIONS: We investigated the effect of different hydroxyethyl starch (HES) solutions (70.000, 130.000, 200.000) on coagulation. Regarding clot formation and retraction, HES 130.000 had some advantages over the other tested HES solutions. Lactated Ringer's solution affected coagulation only minimally, except for the early stage of clot formation.

[Anaphylactic cardiocirculatory failure after intraoperative application of dipyrone]. / Anaphylaktisches Herz-Kreislauf-Versagen nach intraoperativer Metamizolapplikation.

CASE REPORT: In our case, a 48-year-old healthy woman undergoing elective tympanoplasty under general anesthesia received an infusion of 2 g dipyrone in 100 ml 0.9% sodium chloride solution for pain prophylaxis. After receiving 1 g dipyrone within 5 min, the patient exhibited a cardiocirculatory failure and cyanosis and had to be resuscitated. After 20 min of cardiopulmonary resuscitation and administration of 3mg epinephrine and 2 mg norepinephrine, a stable circulation was reestablished. After exclusion of a fulminant pulmonary embolism and a primary cardiac event by computer tomography, electrocardiogram and enzyme diagnostics, the patient was transferred to an intensive care unit where she was mechanically ventilated for a period of 6 h. After 2 days of intensive monitoring, she was transferred to a peripheral ward,where she exhibited a normal neurological status and stable cardiocirculatory condition. A postoperatively performed allergy testing revealed a type I sensitization to dipyrone, which was responsible for the intraoperative cardiocirculatory failure due to a massive anaphylactic reaction. However, in this case, the typical symptoms of allergic reactions such as erythema, edema or bronchospasm were missing, which did not allow for an immediate diagnosis. CONCLUSION. Regarding the frequent perioperative use of dipyrone and the severity of anaphylaxis observed in this case, it should be considered that this analgesic should be applied intravenously only if adequate safety measures such as emergency therapy option and patient monitoring are guaranteed as recommended by the German drug regulation authority since 1982.

Impact of endothelin-1 in endotoxin-induced pulmonary vascular reactions.

OBJECTIVES: Elevated endothelin-1 (ET-1) levels have been detected during sepsis. The aim of the study was to examine the role of thromboxane A2 (TXA2) and ET-1 in pulmonary vascular reactions after endotoxin (LPS) challenge. DESIGN: Prospective experimental study in rabbits. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: Twenty-four adult rabbits of either sex. INTERVENTIONS: Experiments were performed on 30 isolated and ventilated rabbit lungs, which were perfused with a saline solution containing 10% autologous blood. MEASUREMENTS AND MAIN RESULTS: Pulmonary arterial pressure and lung weight gain were continuously registered. Perfusate samples were drawn intermittently to determine ET-1, TXA2, and prostacyclin (PGI2) concentrations. LPS isolated from Escherichia coli (0.5 mg/mL; n = 6) was added to the perfusate. A marked pulmonary arterial pressure increase followed by massive edema formation after 60 mins was observed after LPS injection. At the same time, elevated TXA2 and PGI2 levels in the perfusate were measured. ET-1 was detected 30 mins after LPS infusion (13.4+/-2.6 fmol/L). Pretreatment with the ET(A) receptor antagonist LU135252 (10(-6) M; n = 6) almost completely suppressed the pressure reaction after endotoxin injection (p < .01 at 50 and 60 mins) and reduced edema formation (p < .05). The cyclooxygenase inhibitor diclofenac (10 microg/mL; n = 6) was as effective as LU135252 in preventing vascular reactions after LPS injection. CONCLUSIONS: Pretreatment with the ET(A) receptor antagonist LU135252 and the cyclooxygenase inhibitor diclofenac reduced pulmonary vascular reactions after LPS challenge. Based on the current data, we conclude that the pulmonary arterial pressure increase and edema formation after LPS injection are related to an ET-1- and TXA2-dependent mechanism.

Endothelin-1 impairs neutrophil respiratory burst and elimination of Escherichia coli in rabbits.

OBJECTIVE: During systemic inflammation, elevated levels of endothelin (ET)-1 have been reported. The aim of this study was to investigate the effects of ET-1 on neutrophil (PMN) respiratory burst, phagocytosis, and elimination of Escherichia coli from blood and tissues. DESIGN: Prospective, randomized, controlled trial. SETTING: Experimental laboratory in a university hospital. SUBJECTS: A total of 18 female chinchilla rabbits. INTERVENTIONS: To quantify the clearance process, defined numbers (10(8) colony-forming units) of E. coli were injected intravenously into anesthetized rabbits, 60 mins after onset of continuous 0.2 microg/kg/min ET-1 administration (n = 9) and after saline infusion (control group, n = 9), respectively. To evaluate potential effects of ET-1 on bacterial elimination and killing, blood clearance of E. coli and colonization of different organs were investigated. MEASUREMENTS: Variables monitored were neutrophil respiratory burst and phagocytosis activity, rates of bacterial elimination from the blood, arterial blood pressure, blood gases, serum lactate concentrations, and nitrite and nitrate levels. The animals were killed 3 hrs after bacterial injection and tissue samples of liver, kidney, spleen, and lung were collected for bacterial counts. MAIN RESULTS: Compared with the control group, ET-1 significantly impaired PMN respiratory burst (p < .05) and prolonged elimination of injected E. coli from the blood (p < .01), whereas phagocytosis functions remained unaltered. The reduced PMN burst activity after ET-1 was associated with a higher bacterial colonization of all organs (lung, p < .01; spleen, p < .05). Endothelin-1 induced increases in mean arterial pressure (p < .01) and serum lactate concentrations, whereas nitrite and nitrate levels remained unaltered. CONCLUSION: Endothelin-1 impairs respiratory burst and bacterial clearance from the blood and tissue. Thus, elevated levels of ET-1 during sepsis could induce organ hypoperfusion and cause disturbances in immune functions, increasing the risk of bacterial infections.

Pancreatitis-associated protein protects the lung from leukocyte-induced injury.

BACKGROUND: Severe pancreatitis is often complicated by shock and acute lung failure. Little is known about the pathophysiologic impact of the 16.6-kD lectine, named pancreatitis-associated protein (PAP), which is expressed during pancreatitis and which reduces mortality in a rat model with severe pancreatitis. Therefore, the aim of this study was to investigate the effects of PAP on the pulmonary vasculature after leukocyte activation with N-formyl-Met-Leu-Phe (fMLP). METHODS: The experiments were performed in buffer-perfused isolated rabbit lungs. Mean pulmonary artery pressure, weight gain, and thromboxane A2 synthesis of the lungs were monitored. PAP was obtained by affinity chromatography of pancreas juice from pancreatitic rats. The authors tested whether treatment with PAP (260 microg/l, n = 9; or 500 microg/l, n = 6) before fMLP injection (10(-6) M) influences mean pulmonary artery pressure and edema formation. Lungs that were treated only with fMLP (n = 6) served as controls. Additional experiments in which PAP was applied were performed to study whether PAP (260 microg/l, n = 3; 500 microg/l, n = 3; 1,000 microg/l, n = 3) itself effects lung vasculature. RESULTS: Application of fMLP resulted in an increase of mean pulmonary artery pressure (+/- SD) from 8 +/- 2 mmHg up to 26 +/-13 mmHg (P < 0.01) at a flow of 150 ml/min. Pretreatment with PAP reduced the peak pressure developed after fMLP to 15 +/- 7 mmHg (PAP 260 microg/l; P < 0.05) and to 9 +/- 4 mmHg (PAP 500 microg/l), respectively. In addition, the fMLP-induced lung weight gain of 9 +/- 7 g in the controls was prevented by pretreatment with PAP after 150 min in either concentration. In parallel to the attenuated pressure increase, thromboxane A2 release was significantly suppressed in the 260-microg/l (200 +/- 220 pmol x ml(-1) x min(-1); P < 0.01) and 500-microg/l (285 +/- 70 pmol x m(-1) x min(-1); P < 0.05) PAP groups compared with controls (1,138 +/- 800 pmol x ml(-1) x mi(-1)). Treatment with PAP alone in either concentration did not induce any changes in mean pulmonary artery pressure, weight gain, or thromboxane A2 release. CONCLUSION: Clinically relevant concentrations of PAP prevented fMLP-induced vasoconstriction and edema formation in the lung. These findings point toward a protective effect of PAP on polymorphonuclear neutrophil leukocyte-mediated lung injury.