[Perioperative pharmacological circulatory support in daily clinical routine]. / Perioperative medikamentöse Kreislaufunterstützung in der täglichen Routine.

Perioperative phases of hypotension are associated with an increase in postoperative complications and organ damage. Whereas some years ago hemodynamic stabilization was primarily carried out by volume supplementation, in recent years the use and dosing of cardiovascular-active substances has significantly increased. But like intravascular volume therapy, also substances with a cardiovascular effect have therapeutic margins, and thus, potential side effects. This review article discusses indications for each cardiovascular-active agent, weighing up advantages and disadvantages. Special attention is paid to the question how to administrate them: central venous catheter vs. peripheral indwelling venous cannula. The authors come to the conclusion that it is not a question of whether it is principally allowed to apply cardiovascular-active drugs via peripheral veins but more importantly, what should be taken into consideration if a peripheral venous access is used. This article provides concise recommendations.

Urine neutrophil gelatinase-associated lipocalin predicts outcome and renal failure in open and endovascular thoracic abdominal aortic aneurysm surgery.

Urine neutrophil gelatinase-associated lipocalin (uNGAL) has been evaluated as a biomarker for AKI detection and adverse outcome in open and endovascular thoracoabdominal aortic aneurysm surgery. This observational, retrospective study included 52 patients. UNGAL was measured peri-operatively (48 h) and correlated with AKI requiring dialysis, tracheotomy and adverse outcome. Mean patients' age was 64.5 years. A total of 26.9% (n = 14) developed AKI, and 21.1% (n = 11) required dialysis, tracheotomy rate was 19.2% (n = 10) and in-hospital mortality rate was 7.6% (n = 4). uNGAL levels were related to AKI requiring dialysis at ICU (p = 0.0002), need for tracheotomy at baseline and admission on ICU (p = 0.0222, p = 0.0028, respectively), as well as adverse discharge modality (p = 0.0051, p = 0.0048, respectively). Diagnostic quality was good for uNGAL levels at admission to ICU regarding AKI requiring dialysis (sensitivity: 81.8% [48.2-97.7]; specificity: 87.8% [73.8-95.9]; area under the curve (AUC): 0.874 [0.752-0.949]). The diagnostic quality of uNGAL was favorable for the prediction of tracheotomy (sensitivity: 70.0% [34.8-93.3]; specificity: 83.3% [68.6-93.0]; AUC: 0.807 [0.674-0.903]) and adverse discharge (sensitivity: 77.8% [40.0-97.2]; specificity: 83.7% [69.3-93.2]; AUC: 0.817 [0.685-0.910]). uNGAL may be valuable as an post-operative predictor of AKI and adverse outcome after open and endovascular TAAA repair.

[Heart in sepsis : Molecular mechanisms, diagnosis and therapy of septic cardiomyopathy]. / Herz in der Sepsis : Molekulare Mechanismen, Diagnose und Therapie der septischen Kardiomyopathie.

An impairment of cardiac function is a key feature of cardiovascular failure associated with sepsis; however, its clinical relevance is still underestimated. Recent advancements in echocardiography in patients with septic shock enable a better characterization of septic cardiomyopathy by unmasking a severe, cardiac dysfunction even in the presence of preserved left ventricular ejection fraction. The pathophysiology of septic cardiomyopathy involves a complex mixture of systemic factors and molecular, metabolic, and structural changes of the cardiomyocytes. A better understanding of these factors will enable the discovery of new therapeutic targets for urgently needed disease-modifying therapeutic interventions. To date, the cornerstone of therapeutic management lies in control of the underlying infectious process and hemodynamic stabilization. This review summarizes the pathogenesis, diagnosis, and treatment of septic cardiomyopathy, and highlights the importance of further urgently needed studies aimed at improving diagnosis and treatment for septic cardiomyopathy.

Impact of age on the clinical outcomes of major trauma.

PURPOSE: In view of demographic changes over the past few decades, the average age of trauma patients is progressively increasing. We therefore aimed to summarize the specific characteristics of geriatric trauma and to identify potential fields for further research to improve the care of elderly trauma patients. METHODS: Review of the literature. RESULTS: Due to the diverse risk factors (e.g., pre-existing conditions, limited physiological reserve), geriatric patients are prone to developing severe complications, even after less severe trauma. Yet, age is not considered as the only predictor of worse outcomes, and it should not be considered the only criterion for limiting care in those patients. It is crucial that age-specific treatment guidelines are developed to optimize the outcomes for senior trauma patients. Based on the current literature, these guidelines should emphasize the importance of field triage directly to a trauma center, along with the activation of the trauma team. Furthermore, early intensive monitoring, aggressive resuscitation, and time of surgical intervention are of upmost importance to reduce mortality. CONCLUSION: The impact of several factors [age, premedical conditions (PMC), decreased physiological reserves, and impaired immune function] on the post-traumatic course of elderly trauma patients needs to be clarified in future experimental and clinical studies for the early identification of geriatric high-risk patients and for the development of age-adapted therapeutic strategies.

Compliance with hand hygiene in patients with meticillin-resistant Staphylococcus aureus and extended-spectrum ß-lactamase-producing enterobacteria.

Hand hygiene is considered to be the single most effective measure to prevent healthcare-associated infection. Although there have been several reports on hand hygiene compliance, data on patients with multidrug-resistant (MDR) organisms in special isolation conditions are lacking. Therefore, we conducted a prospective observational study of indications for, and compliance with, hand hygiene in patients colonised or infected with meticillin-resistant Staphylococcus aureus (MRSA) or extended-spectrum ß-lactamase (ESBL)-producing enterobacteria in surgical intensive and intermediate care units. Hand disinfectant used during care of patients with MRSA was measured. Observed daily hand hygiene indications were higher in MRSA isolation conditions than in ESBL isolation conditions. Observed compliance rates were 47% and 43% for the MRSA group and 54% and 51% for the ESBL group in the surgical intensive care unit and the intermediate care unit, respectively. Compliance rates before patient contact or aseptic tasks were significantly lower (17-47%) than after contact with patient, body fluid or patient's surroundings (31-78%). Glove usage instead of disinfection was employed in up to 100% before patient contact. However, compliance rates calculated from disinfectant usage were two-fold lower (intensive care: 24% vs 47%; intermediate care: 21% vs 43%). This study is the first to provide data on hand hygiene in patients with MDR bacteria and includes a comparison of observed and calculated compliance. Compliance is low in patients under special isolation conditions, even for the indications of greatest impact in preventing healthcare-associated infections. These data may help to focus measures to reduce transmission of MDR bacteria and improve patient safety.

[Excessive blood loss after abdominal hysterectomy -- use of recombinant factor VIIa]. / Massive Blutung nach Hysterektomie -- Einsatz von rekombinantem Faktor VIIa.

MEDICAL HISTORY: A 38-yr-old woman suffered from excessive blood loss after elective removal of the uterus because of a leiomyoma. The surgical attempt to stop the bleeding failed. The laboratory evaluation before surgery showed normal coagulation parameters (aPTT 23.4 sec, TPZ > 100 %, platelet count 267 000/microl). DEVELOPMENT: Despite treatment with the plasminogen activator inhibitor Tranexamic Acid (2 x 500 mg) and 10 units of concentrated platelets as well as 31 units of fresh frozen plasma and 31 units of red blood cell concentrates the bleeding continued. Reaching an cumulative blood loss of 15 000 ml the patient developed ventricular fibrillation necessitating cardiac resuscitation including defibrillation and application of epinephrine 7 mg. At this point systolic blood pressure decreased from 90 to 70 mm Hg, the core temperature was 31,9 degrees C. After successful resuscitation (systolic blood-pressure 90 mm Hg after 15 min) the bleeding started again with a blood loss of 2000 ml requiring 3 units of fresh frozen plasma and 3 red cell concentrates Use of recombinant activated Factor VII (r.FVIIa): 6 mg (300 KiU) r.FVIIa have been applied (92 microg/kgKG [4.6 KiE/kg]). Within 10 minutes the bleeding stopped. More transfusions were not necessary. The patient left the intensive care unit 8 days after the operation without neurological deficit. CONCLUSION: The use of recombinant Factor VIIa may stop excessive haemorrhage, even if the cause is unknown.

Impact of tobacco smoking on platelet function in apheresis products in vitro.

BACKGROUND AND OBJECTIVES: The aim of this study was to analyse the platelet function, over a 5-day time-period, of apheresis-derived platelet concentrates obtained from smokers and non-smokers. MATERIALS AND METHODS: Smoker and non-smoker plateletpheresis products were investigated on days 1, 3 and 5 of storage. Receptor expression (as evaluated by flow cytometry) and the platelet aggregation response were measured. RESULTS: There was only a slight loss of platelet function in apheresis products from smokers compared to non-smokers. CONCLUSIONS: Smoking does not significantly change the quality of platelet preparations. The current practice, of not to exclude smokers from platelet donation, can be continued.

[Massive transfusion of washed red blood cells: acid-base and electrolyth changes for different wash solutions]. / Massivtransfusionen mit gewaschenen Erythrozyten: Beeinflussung des Säure-Basen-Elektrolyt-Haushalts durch verschiedene Waschlösungen.

OBJECTIVE: The composition of normal saline (NaCl), the standard wash solution for cell saver autotransfusion, is considerably different from physiologic plasma values in small infants. Therefore, we investigated acid-base and electrolyte changes during massive cell saver autotransfusion with different wash solutions in young pigs. METHODS: After approval by the animal protection authorities 15 young pigs (weight 10.6 +/- 1.1 kg, blood volume 848 +/- 88 ml, mean+/-SD) underwent 15 cycles of cell saver autotransfusion (Haemolite 2plus, Haemonetics). For each cycle, 100 ml arterial blood was withdrawn, washed with NaCl, physiologic multielectrolyte solution (PME, V Infusionslösung 296 mval Elektrolyte, Baxter) or physiologic erythrocyte protection solution (PEP, 3.2 % gelatine, pH 7.40, cHCO3 24 mmol/l), and then retransfused. Analyses of acid-base, electrolyte, and hematologic parameters were performed for systemic and washed blood samples. RESULTS: For NaCl there was a progressive decrease in systemic pH, HCO3 and base excess (BE) and an increase in chloride values (Cl) (p < 0.05). Use of PME slightly decreased pH (n. s.), whereas HCO3, BE and Cl remained stable. PEP slightly increased pH, HCO3 and BE, and decreased Cl (n. s.). Free hemoglobin increased in NaCl and PME (p < 0.05) and was below baseline in PEP (n. s.). Lactic acid course was comparable in all groups. CONCLUSIONS: The use of NaCl as wash solution for massive autotransfusion resulted in metabolic acidosis caused by dilution of HCO3 and increased Cl values. Fewer systemic acid-base and electrolyte changes were observed, when blood was washed with PME or PEP. The decreased hemoglobin release with PEP is possibly due to a gelatine specific electrostatic surface coating of erythrocyte membranes. For massive transfusion of washed red blood cells, physiologic multielectrolyte solution and physiologic erythrocyte protection solution should be preferred to NaCl, especially for small infants.

[Aseptic central venous catheter exchange with a guide wire]. / Aseptischer Wechsel des zentralen Venenkatheters über einen Führungsdraht.

Central venous catheters are exchanged in cases of malfunction, suspected infections, or when another catheter type is required. It can be replaced by new venipuncture or using a guide wire. The guide wire technique should be used with a defective catheter or when the catheter type is to be changed. It is contraindicated at exit site infections or proven or suspected catheter infections. Due to possible cross contamination of new by old catheter material meticulous aseptic technique is required. A detailed description of the process of catheter exchange using a guide wire with special regard to the aseptic technique is given.

Acid-base, electrolyte and metabolite concentrations in packed red blood cells for major transfusion in infants.

METHODS: Acid-base, electrolyte and metabolite concentrations were determined in 100 U of packed red blood cells (RBC) preserved in extended-storage media to be used for major transfusion in paediatric and cardiac surgery. RESULTS: In fresh RBC, low pH, bicarbonate (cHCO3-), base excess (BE) and high glucose values were observed all outside the physiological range. With lengthening storage duration, values of pH, cHCO3-, BE, sodium and glucose decreased and carbon dioxide, potassium and lactic acid concentrations increased [mean +/- SD (range): storage duration 6.7 +/- 3.8 (1-17) days, pH 6.79 +/- 0.1 (6.53-6.99); mmol.l-1: cHCO3- 11.1 +/- 1.5 (6.2-14.5), BE - 29.2 +/- 4.1 ([-39.4] - [-20.9]), potassium 20.5 +/- 7.8 (4.2-43.6), glucose 24.1 +/- 6.1 (16.7-29.2), lactic acid 9.4 +/- 4 (4.3-21.4)]. CONCLUSION: Massive and rapid transfusion of RBC may lead to a severe burden of hydrogen ions, carbon dioxide, potassium, glucose and lactic acid and this can be avoided by cell saver blood processing, when autologous erythrocytes from the operative field are saved and substrate load and storage lesions from packed red blood cells are minimized in one step by washing.

Protective effects of plasma replacement fluids on erythrocytes exposed to mechanical stress.

Haemoglobin release from 40 suspensions of packed red blood cells in modified fluid gelatin, 4% albumin solution, 6% hydroxyethyl starch and normal saline was investigated in vitro during circulation with a roller pump from a heart-lung machine for 120 min at a flow rate of 2.5 l.min-1 at room temperature. The lowest haemoglobin release was obtained with erythrocytes in modified fluid gelatin, whereas free haemoglobin concentrations became progressively higher with albumin, hydroxyethyl starch and normal saline [median free haemoglobin (interquartile range) after 120 min circulation: gelatin 493 (360-601) mg.l-1, albumin 692 (590-1111) mg.l-1, hydroxyethyl starch 1121 (692-1518) mg.l-1, normal saline 1178 (881-1757) mg.l-1, p < 0.001]. Modified fluid gelatin appears to have potent erythrocyte protective properties similar to those of albumin. This effect could decrease mechanical haemolysis during extracorporeal circulation or cell saver autotransfusion if modified fluid gelatin is used as part of a priming solution or as an additive in wash solutions.

Evaluation of modulations in heart rate variability caused by a composition of herbal extracts.

The purpose of this prospective, placebo-controlled, randomized double-blind study was the examination of changes of the basic vegetative rhythms due to Cardiodoron, a composition of extracts of blossoms from Primula officinalis and Onopordon acanthium and from the herbs of Hyoscyamus niger. In its clinical use it is known as a modulating medicine in the treatment of functional disturbances of the cardiovascular system. With use of Holter monitoring, 24-h ECG recordings were obtained from 100 healthy subjects of whom 50 took the composition and 50 a placebo. Heart rate variability was evaluated from the 24-h ECGs by means of a power spectral analysis based on the Fast Fourier Transformation (FFT). Regulative influences on the rhythmic system due to the medicine were found. After four weeks of medication half of the verum group showed a tendency to an increased variability in the low and high frequency range at night (LFn: 0.04-0.15 Hz, HFn: 0.15-0.4 Hz) in contrast to the placebo group. The mean heart rate at night (HRn) showed a tendency towards a normalization in the verum group: in subjects with a low HRn the heart rate was increased and in subjects with a high HRn the heart rate was decreased. This effect could not be observed in the placebo group. After two further weeks without any medication this difference between verum and placebo was abolished.

Haemodynamic, acid-base and electrolyte changes during plasma replacement with hydroxyethyl starch or crystalloid solution in young pigs.

We investigated haemodynamic, acid-base and electrolyte changes during almost total plasma replacement with hydroxyethyl starch (HES) and physiological balanced electrolyte solution (PBE) by using a cell saver in ten young pigs. In the PBE group an additional 3550 (444) ml crystalloid solution [Mean (SD)] was infused over the course of the study in order to maintain pulmonary capillary wedge pressure. Plasma protein levels decreased in both groups and the colloid osmotic pressure increased in HES and decreased in PBE. At the end of the study, body weight [HES 10.4 (1), PBE 13.1 (1.4) kg, P < 0.01] and lactic acid concentration [HES 0.9 (0.3), PBE 2.9 (1. 3) mmol.l -1, P < 0.01] was higher and tissue oxygen delivery [HES 327 (22), PBE 89 (29) ml.min.m2, P < 0.01] was lower in the PBE group. There were only moderate acid-base changes in both groups, but at the end, anion gap was significant lower in HES. In conclusion, maintenance of colloid osmotic pressure close to the physiological range of infants seems to be advantageous during major paediatric surgery.

[The effect of a nasal spray consisting of a standardized mixture of citrus limon (succus) and an aqueous extract of Cydonia oblongata (fructus) on nasal mucociliary clearance]. / Einfluss eines Nasensprays bestehend aus einer standardisierten Mischung von Citrus limon (succus) und eines wässrigen Auszugs aus Cydonia oblonga (fructus) auf die nasale mukoziliäre Clearance.

In a three-way-crossover study in 18 healthy male and female subjects aged from 20 to 49 years the influence of a 1% and 3% solution of a standardized composition of Citrus limon, succus, and extract from Cydonia oblonga, fructus (Gencydo) on the intranasal mucociliar clearance was investigated after multiple administration. The pH of the solution was about pH 2.3-3.2. The dose regimen consisted of 20 puffs (0.13 ml per puff) in each nostril within 24 h, which was by factor 3-10 higher than the usual therapeutic dosage of 2-6 puffs per nostril and 24 h. The mucociliar transport time was measured by a modified saccharin test, where 1 microliter of a 3-molar aqueous sodium saccharinate solution was applicated at the inferior nasal turbinate 1 cm from its anterior end using a glass capillary microliter pipet. This test was performed at screening examination, before each administration period, directly after each 24 h treatment period and 24 h after the end of each treatment. The time of initial taste perception could be defined with high precision by the volunteer since it appeared very spontaneously. Neither after intranasal administration of the 1% and 3% Citrus/Cydonia solution nor after placebo solution a prolongation of the perception time was found. It could be concluded that there is no measurable influence of the test products on the intranasal ciliar function.

Alteration of anion gap during almost total plasma replacement with synthetic colloids in piglets.

In ten piglets (body weight 8.2-11.6 kg), acid base, electrolyte and anion gap changes were investigated during almost total plasma replacement with hydroxyethyl starch (HES) and modified fluid gelatin (GEL) in saline solution using a cell saver autotransfusion technique. During the study, there were only moderate acid base changes, but marked disturbances in anion balance. At study end, the mean chloride concentration was significantly higher (mmol/l: normal values 97-108, HES 116 +/- 1.5, GEL 108 +/- 1.1, p < 0.01) and the mean anion gap was significantly lower in the HES group in comparison to the GEL group (mmol/l: normal values 5-14, HES 3 +/- 1.7, GEL 11.9 +/- 0.9, p < 0.01). It is concluded that plasma replacement with electroneutral HES, but not with negatively charged GEL, can lower the anion gap irrespective of the underlying disease. This can be misleading when the anion gap is used for differential diagnosis of metabolic acidosis in patients after large volume infusion of synthetic colloids.

The initiation of the muscle action potential.

The specific functional properties of the nicotinic acetylcholine receptors (AChR) and the particular oligomeric membrane organization of AChR are suggested to be the basis for the steep electrical depolarisation, required for the initiation of the postsynaptic action potentials causing muscle contraction and discharge of electric organs. The dimer (M(r) approximately 580,000) and the monomer (M(r) approximately 290,000) of the detergent-solubilized, affinity-purified AChR of Torpedo californica electrocytes exhibit different channel conductances and larger oligochannels. Patch clamp data of the dimer, reconstituted in large lipid vesicles, show that the dimer is a double-channel protein causing single-channel events of conductance G(D) = 84 +/- 6 pS at 0.11 M K+ and 0.1 mM Ca2+ at 293 K (20 degrees C). At the same ionic conditions the vesicle-reconstituted monomer, if prevented from aggregation, exhibits a channel conductance, G(M) = 42 +/- 3 pS, which is only half of that of the dimer. The dimer conductivity event thus reflects the synchronous switching of its two constituent monomeric parts. The K(+)-conductance of the reconstituted Torpedo dimer is the same, and shows the same inhibitory Ca(2+)-dependence, as that of the Torpedo AChR expressed in Xenopus laevis oocytes (Imoto et al., Nature, 324, 670-674, 1986). In terms of Ca(2+)-binding, reducing K(+)-transport, the equilibrium constant is KCa = 0.48 mM at 0.11 m K+, 20 degrees C; G0([Ca]-->0) = 98 +/- 6 pS and G infinity ([Ca]-->infinity) = 27 +/- 6 pS. The ratio G0/G infinity and an estimate of the lateral surface area of the channel vestibule yields about 16 negatively charged groups in an average distance of 1.8 nm. These negative charges cause an accumulation of K+ ions in the channel vestibule by a factor of about 4. Our results and the comparison with the oocyte data reveal that it is also the dimer which is the physiological opening-closing unit of the AChR in the oocyte membrane. The larger macrochannel events are multiples of the dimer or of the monomer conductances. The occurrence of such oligochannels from AChR protein oligomers could guarantee the steep electrical depolarisation necessary to generate the action potential by the Na(+)-channel system.

[Clinical relevance of incidental prostate carcinoma. A retrospective study]. / Klinische Relevanz des inzidentellen Prostatakarzinoms. Eine retrospektive Analyse.

Between July 1973 and December 1992, 5156 men underwent either TURP (n = 4259) or open prostatectomy (n = 897) because of infravesical obstruction supposedly due to benign prostatic hyperplasia (BPH). In this retrospective study, 86 men in whom an incidental carcinoma of the prostate had been found were followed up. Thirty-seven cases had been classified as pT1a tumor and 49 cases as pT1b tumor; 73 patients had undergone TURP and 13 open surgery. The mean age of the patients was 70.6 years (range 54-89). Twenty-seven patients (73%) with a pT1a tumor and 19 patients (38.8%) with a pT1b carcinoma received no further treatment. Radical prostatectomy was performed in four cases, one of pT1a and three of pT1b tumor. In all other cases the patients received androgen deprivation, and in four cases external radiotherapy was applied. With a mean follow-up of 5 years (range 17-229 months) 48 patients died (55.8%). The median survival was 73 months (95% CI: 52; 89). Compared to the overall population in the same age range, the standard mortality rate (SMR) was 1.72 and 2.05 (95% CI: 1.23; 2.21 and 1.46; 2.64 respectively) using the "Allgemeine Sterbetafel" of the Federal Republic of Germany (1949-1951 and 1986-1988). Using the log-rank test (P = 0.5, two-sided) no difference in survival was found between patients staged pT1a and pT1b. Ten of 48 patients dead at the time of evaluation died of prostate cancer. This means that 20.8% (pT1a n = 3; pT1b n = 7) of the patients succumbed to progressive disease during follow-up. All four patients who underwent radical prostatectomy are free of tumor at time of this evaluation. These results are in accordance with other studies. In younger men with incidental carcinoma of the prostate and life expectancy of more than 10 years, radical surgery of the prostate should be recommended.

Purification of the CIC-0 chloride channel from Torpedo california electroplax identification of a phosphorylation site for cAMP-dependent protein kinase.

The voltage-gated chloride channel (CIC-0) from the electric organ of Torpedo californica was purified by immunoaffinity chromatography. A polyclonal antibody was shown to specifically recognize the CIC-0 channel (M(r) 85,000-90,000) in a Western blot of total membrane proteins. As monitored by immunoprecipitation, the formation of antibody-antigen complexes in solution strongly depends on the detergent composition. The highest yield of precipitated CIC-0 was obtained from an incubation mixture containing both an anionic detergent, cholate or lauryl sulfate, and the zwitterionic detergent CHAPS. In contrast, immuno-precipitation of CIC-0 was largely reduced when cholate was exchanged for the nonionic detergent Triton x-100, suggesting that the efficient formation of immuno-complexes is favored by negatively charged detergent. In initial immunopurification experiments, in addition to CIC-0 a major contaminating polypeptide of M(r) approximately 115,000 was copurified, which represents the SITS-binding protein [Jentsch et al. (1989) Biochem. J. 261, 155]. Purification of CIC-0 could be increased from about 35% up to 60% homogeneity when immunoaffinity chromatography was performed in the presence of N-acetylglucosamine. Therefore the highly glycosylated SITS-binding protein most likely interacts with the CIC-0 protein via its carbohydrate parts. The purified CIC-0 channel was found to be phosphorylated by PKA in vitro to a level of 0.35-0.4 mol of phosphate incorporated per mol of CIC-0. Proteolytic digestion with endoproteinase GluC and HPLC-separation revealed two major phosphopeptides, which could be identified by amino acid sequence analysis as different size fragments of the same consensus phosphorylation site. Comparison of the peptide sequences with the deduced protein sequence of CIC-0 [Jentsch et al. (1990) Nature 348, 510; O'Neill et al. (1991) Biochem. Biophys. Acta 1129, 131] indicates serine 600 as the phosphorylated residue. Therefore, our results provide strong evidence that CIC-0 is phosphorylated at this single site by PKA in vitro.