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Seit Einfuhrung der Fallpauschalen hat sich die im internationalen Vergleich hohe Verweildauer der Patienten in den deutschen Krankenhausern deutlich verkurzt. Die Arbeit pruft durch empirische Untersuchungen die Hypothese, dass bereits wenige zentrale Kenngrosen fur eine Steuerung ausreichen und ob die Verweildauer ein Effizienz-Indikator sein kann. Grundlagen der Analysen waren Leistungsdaten von 20 deutschen Krankenhausern fur 2007–2009 (963 923 berucksichtigte stationare Falle) sowie Kostendaten der Hauser fur 2007–2010. Uber Modelle der einfachen und der schrittweisen multiplen linearen Regression wurde der Einfluss von Fall- und Mengenfaktoren auf den Case Mix Index (CMI) und auf Kostenartengruppen bewertet. Im multiplen Modell korrelierte die Verweildauer mit dem CMI mit einem Regressionskoeffizienten von β=0,488 (p

Since introduction of the German refined DRG system, the, in relation to other countries, relatively long hospital stay has been reduced significantly. The analyses presented here examine the hypothesis that only few impact factors allow for good hospital management and that length of stay is a performance indicator. The analyses were based on remuneration data of 20 German hospitals for 2007-2009, comprising details of 963 923 patient cases, and cost data for 2007-2010. Using simple and multiple linear regressions, the impact of hospital length of stay and case-based factors on case mix index (CMI) and cost categories were explained. The variance of the case mix index was best explained by the length of hospital stay, showing an adjusted regression coefficient β=0.488 (p0.001), followed by the number of coded procedures (β=0.35, p0.001). Other predictors played a minor role. The regression coefficient was higher for conservative (non-operative) than for surgery (operative) departments. In the regression on costs, the length of hospital stay explained the variance of total costs by β=0.391 (p0.001), among these personnel costs of the nursing staff correlated most highly (β=0.595, p0.001). The analyses confirm the working hypothesis with length of stay impacting CMI and costs most significantly. Treatment effort and complexity level, mortality rate, patient age or gender are well discussed factors but their joint impact on the CMI is minor. Consequently, cockpits for operational length of stay management comprising key data and ratios should be introduced on the department level.

Tumour necrosis factor alpha (TNF alpha) is increased in patients with cardiac cachexia, a condition associated with reduced peripheral blood flow both at rest and after interventions causing vasodilation. By contrast, in patients with chronic heart failure (CHF), higher TNF levels are associated with a greater capacity for vasodilation in the arm. To clarify the relationship between peripheral blood flow and TNF in CHF, we studied the relation between TNF alpha and blood flow in the leg (plethysmography, post maximal exercise and 5 min ischaemia) in 34 patients (age 63 +/- 2 years, ejection fraction 29 +/- 3%, peak VO2 16.6 +/- 1.1 ml/kg/min, mean +/- SEM). Peak leg blood flow correlated significantly with total TNF alpha (r = 0.68, p < 0.0001, peak VO2 (r = 0.54), and soluble TNF receptors 1 (r = 0.56) and 2 (r = 0.52, all p < 0.002). TNF alpha, soluble TNF receptors 1 and 2 and aldosterone correlated with peak blood flow independently of age, ejection fraction, peak VO2 and functional NYHA class. TNF alpha was the only parameter that showed strong correlations for peak blood flow in all clinically relevant subgroups (severe vs. mild, ischaemic vs. dilated, cachectic vs. non-cachectic patients). This study shows a close and inverse relationship between peak leg blood flow and the plasma concentration of TNF alpha, suggesting a pathophysiological role for TNF alpha in reducing peak peripheral blood flow in CHF.

Changes in gas viscosity during the nitrogen washout test will affect pneumotachograph measurements. A digital correction technique, using estimates of viscosity derived from measurements of gas concentration, has been described and was examined in this study. The pneumotachograph gain varied directly with argon concentration (coefficient of correlation = 0.995, P less than 0.01) indicating that a simple correction was legitimate. This was tested with an in vitro model, giving very consistent estimates of volume (FRC) despite variations in the ventilation pattern, which were slightly underestimated due to incomplete mixing in the system. Alveolar mixing efficiency (AME) was also reproducible but, like studies in man, fell when low tidal volumes were used. In a repeatability study in six volunteers, examined six times on each of two days, FRC and AME were also reproducible (average coefficient of variation within subjects of 4.97% and 4.34% respectively), considerably better than another reported study using conventional flow measurements. This method appears to be a useful addition to existing techniques for studying nitrogen washout.

Duplex Doppler ultrasound (DDU) was used to study the blood flow characteristics of the renal interlobar artery in 20 subjects with acute renal failure (ARF), 14 subjects with transient impairment of renal function and 23 control subjects with normal function. Renovascular resistance was assessed by pulsatility index (PI) and change in flow velocity by change in mean frequency shift (delta f). The 99% confidence intervals for PI in the three groups were 3.32-5.46, 1.58-2.34 and 0.99-1.33 respectively. Values for delta f were 0.2-0.38, 0.5-0.62 and 0.7-1.02 kHz respectively. Ten ARF patients recovered function, 99% confidence intervals for PI just prior to recovery were 0.9-1.48 and for delta f 0.52-1.02 kHz. There was increased renovascular resistance and reduced intrarenal blood flow velocity at the onset of ARF. These changes persisted during ARF; recovery of function occurred after they returned to normal. Similar, but less marked, changes were found in patients with a transient impairment of function.

We used quantitative analysis of the electroencephalogram (EEG) during routine clinical practice to assess the effect of tracheal intubation following induction of anesthesia with propofol and fentanyl.The topographic EEG was recorded from eight bipolar electrode derivations in 25 patients. Z-scores relative to age expected normative data were computed for relative power in the delta, theta, alpha and beta frequency bands. Multivariate statistics (Hotellings' t-sqare) were used to evaluate changes in regional brain electrical activity.Tracheal intubation induced an increase in alpha and beta frequencies, while delta power was reduced (F-values: Delta: 7.68, p = 0.011; Alpha 31.93; p0.001; Beta 12.85, p = 0.001). The most pronounced regional effect was seen for the alpha frequency band with the largest increase in both fronto-temporal regions (F-value 33.89, p0.001). During clinical practice the patients received propofol 2.7 (+/- 1.2; minimum: 0.5, maximum 6.9) mg kg (- 1) and fentanyl 2 (+/- 1; minimum 1, maximum 4) microg kg (- 1). Vital parameters did not change during intubation.Individual titration of the dose of propofol and fentanyl as done during routine clinical practice is not sufficient to block the strong noxious stimulation of intubation. Tracheal intubation resulted in "classical" cortical arousal. It remains open whether this cortical wake-up phenomenon has a clinical impact.

In the present study the "fast-track rehabilitation" protocol of the Charité university hospital for patients undergoing elective colonic resection is described. The underlying principles, clinical pathways and outcome data from 208 patients are shown. Particularly anesthesiological aspects of this multimodal approach, such as modified preoperative and postoperative fluid management, changed guidelines for preoperative fasting, effective analgetic therapy using epidural analgesia and avoiding high systemic doses of opioids, use of short-acting anesthetic agents, and maintenance of normothermia as well as normovolemia are presented and discussed. In comparison to outcome data before "fast-track rehabilitation" was established, the duration of postoperative hospital stay has been reduced from 12 to 5 days, the number of general complications (pneumonia, duodenal ulcer bleeding, urinary tract infection, cerebral, cardiac and renal dysfunction) decreased from 20% to 7%, whereas surgical complications remained constant at 17% (8% wound infections, 3% anastomotic insufficiency).

Caused by structural changes in health care the general need for cost control is evident for all hospitals. As operating room is one of the most cost-intensive sectors in a hospital, optimisation of workflow processes in this area is of particular interest for health care providers. While modern operating room management is established in several clinics yet, others are less prepared for economic challenges. Therefore, the operating room statute of the Charité university hospital useful for other hospitals to develop an own concept is presented. In addition, experiences made with implementation of new management structures are described and results obtained over the last 5 years are reported. Whereas the total number of operation procedures increased by 15 %, the operating room utilization increased more markedly in terms of time and cases. Summarizing the results, central operating room management has been proved to be an effective tool to increase the efficiency of workflow processes in the operating room.

For perioperative anesthesia in a case of shoulder arthroscopy, a continuous interscalene plexus block according to Meier was performed in a 51-year-old female patient. The catheter was placed after stimulator-assisted punction and application of a local anesthetic. A few minutes after a further dose of local anesthetic was given via the catheter, the patient had to be intubated and ventilated with signs of total spinal anesthesia. The cervical CT showed the intrathecal displacement of the catheter, reaching the spinal canal near the root of the 7th spinal nerve. Blind advancement and deep placement increase the risk of an abnormal catheter position. Intraspinal misplacement should be reliably excluded.

In Germany the predominant standard of preoperative care for elective surgery is fasting after midnight, with the aim of reducing the risk of pulmonary aspiration. However, for the past several years the scientific evidence supporting such a practice has been challenged. Experimental and clinical studies prove a reliable gastric emptying within 2 h suggesting that, particularly for limited intake of clear fluids up to 2 h preoperatively, there would be no increased risk for the patient. In addition, the general incidence of pulmonary aspiration during general anaesthesia (before induction, during surgery and during recovery) is extremely low, has a good prognosis and is more a consequence of insufficient airway protection and/or inadequate anaesthetic depth rather than due to the patient's fasting state. Therefore, primarily to decrease perioperative discomfort for patients, several national anaesthesia societies have changed their guidelines for preoperative fasting. They recommend a more liberal policy regarding per os intake of both liquid and solid food, with consideration of certain conditions and contraindications. The following article reviews the literature and gives an overview of the scientific background on which the national guidelines are based. The intention of this review is to propose recommendations for preoperative fasting regarding clear fluids for Germany as well.

To evaluate the effect of dopexamine and iloprost on the plasma disappearance rate (PDR) of indocyanine green (ICG) in patients in septic shock in a prospective clinical trial.In 40 consecutive patients in septic shock, a femoral arterial fiberoptic catheter (COLD system) and a gastrotonometric probe were placed. Patients received either dopexamine infusion (0.5 microgram/kg body weight/min) or iloprost (1 ng/kg body weight/min) for 24 h i.v. PDR, intramucosal pH of stomach wall (pHi), cardiac index (HI) and intrathoracic blood volume (ITBV) were determined before, 1, 6, and 24 h after dopexamine or iloprost infusion and 1 h after end of infusion.PDR was significantly increased 24 h after starting dopexamine infusion from 12.2 +/- 1.8%/min to 17.8 +/- 2.2%/min (+45.9%) and 1 h after the end of infusion PDR decreased to baseline values. PDR increased to 16.4 +/- 2.1%/min, 1 h after starting iloprost infusion and increased to a maximum value of 18.6 +/- 2.2%/min (+33.8%, p0.05) 24 h after start of infusion compared to the baseline (13.9 +/- 1.7%/min). After the end of infusion PDR decreased to baseline values. Baseline values of pHi were in normal ranges in all groups and there was no change during the observation period. Cardiac index and ITBV were stable during the study. Dosage of norepinephrine could be reduced by dopexamine infusion.Dopexamine and iloprost have a positive effect on the plasma disappearance rate of ICG and therefore have a protective effect on splanchnic perfusion and liver function, respectively.

Elements of the "open lung concept" are being increasingly included in clinical ventilatory strategies. Despite encouraging experimental investigations to date, relatively few studies exist that examine the clinical application of the complete concept. The aim of this study was to prove that with effective recruitment maneuvers and titrated PEEP levels this concept is applicable in clinical settings. We sought to determine if it was possible to achieve a significant improvement in oxygenation and also to examine what side-effects resulted. Twenty consecutive patients who had had an acute lung injury (ALI) for less than 72 hours, with an oxygenation index (P/F-Ratio = quotient from arterial partial pressure of oxygen [PaO2] and the inspiratory fraction of oxygen [FiO2]) of less than 200 torr, and with a PEEPor = 10 cmH2O were treated using a recruitment manoeuvre (RM). A PEEP was titrated to keep the lung open, and the patients were kept under pressure-controlled ventilation. The P/F-Ratio increased while using a recruitment pressure of 66 +/- 13 cmH2O from 137 +/- 41 to 381 +/- 150 torr (p0.001). The titrated PEEP which kept the lung open after recruitment was 17 +/- 3 cmH2O. One patient developed a pneumothorax. The dose of norepinephrine was increased in ten patients from 0.24 +/- 0.12 to 0.31 +/- 0.1 microgram/kg/min. Due to elevated liver enzymes within the first 48 hours, titrated PEEP had to be decreased in three patients. The clinical application of the "open lung concept" demonstrated a quick and effective improvement in oxygenation in many patients. Side-effects in some patients limited the use of high PEEP levels.

23% of all septic patients develop septic encephalopathy which is associated with an increased mortality rate. Symptoms such as agitation, confusion and disorientation ranging from stupor to coma often develop in early sepsis. Severe hypotension is significantly associated with the development of septic encephalopathy. Several other factors which may play a role are also discussed: effects of inflammatory mediators on the brain, inadequate cerebral perfusion pressure, blood-brain barrier derangements, disturbances of the cerebral microcirculation, cerebral ischemia e.g. due to hypocapnia,metabolic changes, altered amino acid levels, transmitter imbalances, liver insufficiency, multiple organ failure and infections of the CNS, respectively. Compared to patients with an isolated infection,patients in septic shock have increased levels of aromatic amino acids such as phenylalanine and tryptophan in the plasma and brain as well as decreased levels of branched chain amino acids. Patients who died had higher levels of aromatic amino acids than the survivors. The correlation between aromatic amino acids and the APACHE II score was significant. The tryptophan metabolite quinolinic acid which can be synthesized in activated macrophages could act as an excitatory transmitter on the N-methyl-D-aspartate (NMDA) -receptor. Observations from experimental models indicate that activated NMDA receptors activate the neuronal isoform of the NO-synthase and other calcium dependent enzymes. This releases free radicals which may damage the DNA and activate the nuclear enzyme Poly-ADP-ribose-synthetase (PARS), resulting in energy depletion and cell death. Sepsis is the main cause of metabolic encephalopathies in critically ill patients. The differential diagnoses include hepatic, renal,hypoxic-ischemic or cardiovascular encephalopathies as well as encephalopathies,metabolic disorders and organ dysfunctions of other origin. Therapeutic interventions are numerous,however, so far only investigated in few controlled studies. The primary therapeutic goal is to maintain an adequate perfusion pressure and to prevent hypoxia and hypocapnia. Although the infusion of branched chain amino acids is controversial, experimental investigations demonstrated improvements improvements in an animal model with septic encephalopathy. Further investigations with respect to glutamate receptor antagonists, new radical scavengers, NO- and PARS-inhibitors may show whether these substances are suitable for the prophylaxis or early therapy of septic encephalopathy.

Severe sepsis and septic shock are still the leading causes of death in the surgical ICU. The only curative therapies of sepsis are still surgery as well as antibiotic therapy to cure the focus. In addition a supportive therapy (analgesia and sedation, mechanical ventilation, titrated volume substitution and positive inotropes/vasopressor support, parenteral and enteral neutron, renal replacement therapies) should be started as early as possible. A new promising approach in sepsis therapy is the application of rhAPC. The PROWESS study revealed a significantly lower 28 day mortality in patients with severe sepsis who received drotrecogin alfa (activated) compared to patients not treated with drotrecogin alfa (activated). Guidelines for the use in severe sepsis and septic shock in surgical patients (risk of bleeding, costs) are strongly recommended.

In alcohol-dependent in-patients, an adequate drug prophylaxis should be made in order to lower the degree of a developing alcohol withdrawal syndrome (AWS) or to prevent a life-threatening delirium tremens. Pre-condition of successful therapy is a precise diagnosis. In patients, the beginning of whose abstinence is known, carefully-targeted pharmacological interventions can prevent severe imbalances of neurotransmitters. Typical time courses of destabilisation of neural balances should be considered. Since there is no single drug which is able to influence various transmitter systems, normally the use of drug combinations is necessary. In ENT-patients, traumatologic patients and patients from the department of maxillo-facial surgery, screening methods based on a simply-structured questionnaire relating to information from the patient and his surroundings and selected laboratory parameters should be used. High-risk patients who could get an AWS or delirium tremens should be treated prophylactically during their oral premedication period. Important drugs for successful prophylaxis of an AWS are benzodiazepines, clonidin, magnesium and vitamin B 1. A close-meshed control of the glucose metabolism, electrolyte and acid-base balance should be performed. Neuroleptica can be used if there is any indication for their adjuvant use. In severe cases that require deep sedation or hypnosis, propofol or gamma-hydroxy-butyric acid should be used. Perioperative infusion of alcohol as a prophylactic agent against delirium tremens is regarded as an obsolete therapeutic measure for ethical reasons and because equally good or better results can be achieved by carefully-targeted drug therapy. Due to its easy use, however, the application of alcohol has not yet completely disappeared from the therapeutic spectrum.

Several elements of the "open lung concept", like ventilation with small tidal volumes, were incorporated into various ventilatory strategies. Our study demonstrates how the whole concept can be applied in an animal model using a standardized protocol with the following possible results. Eighteen pigs weighing between 30 and 45 kg were anaesthetized, tracheotomized and ventilated. Acute lung injury was induced by surfactant washout. Blood gases were monitored via a continuous arterial sensor system (Trendcare system). After washout, the ventilatory pattern of the American "ARDS Network study" was applied (PEEP = 9 cmH2O, volume controlled mode with a tidal volume of 6 ml/kg body weight and a respiratory rate of 25 breaths per minute). Afterwards, the opening pressure and the pressure at which the lung collapses were titrated. Both levels were used as the basis for adjusting the recruitment pressure and PEEP, which was necessary to keep the lung open. The respiratory rate was chosen in such a way that at a low intrapulmonary pressure difference between inspiration and expiration as well as normocapnia was reached. After induction of an acute lung injury by surfactant washout, the oxygenation index (OI) dropped from 556 +/- 54 to 176 +/- 89 mmHg. In the "ARDS Network" mode, OI increased to 285 +/- 49 mmHg. After alveolar recruitment with a peak pressure of 53 +/- 7 cmH2O and application of a median PEEP of 17 +/- 3 cmH2O, oxygenation returned close to baseline. A pCO2 of 33 +/- 4 mmHg resulted after using a respiratory rate of 39 breaths per minute. The median tidal volume was 8 ml/kg body weight. Despite a short arterial systolic blood pressure drop of 23 +/- 11 mmHg during recruitment, no significant difference was detectable afterwards compared to the baseline. Using low tidal volumes alone, complete reopening was not achieved in an experimentally induced acute lung injury. After recruitment manoeuvres, it was possible to reopen the lung and keep it open by application of a sufficient PEEP.

Die schwere Sepsis und der septische Schock mit Multiorganversagen sind die fuhrenden Todesursachen auf operativen Intensivstationen. Die einzige kurative Therapie der Sepsis ist immer noch die operative Fokussanierung plus die antimikrobielle Therapie. Zusatzlich sollte mit einer supportiven Therapie (Analgesie/Sedierung, mechanische Beatmung, differenzierte Volumen- und Vasopressor-/Inotropika-Therapie, (par)enterale Ernahrung, Nierenersatz-verfahren) so fruh wie moglich begonnen werden. Ein neuer Ansatz in der Therapie der schweren Sepsis ist die Gabe von rhAPC. So konnte in der PROWESS-Studie gezeigt werden, dass Drotrecogin alfa (aktiviert) zu einer signifikanten Senkung der 28-Tage-Gesamtletalitat bei Patienten mit schwerer Sepsis fuhrt. Therapierichtlinien fur die Anwendung von Drotrecogin alfa (aktiviert) bei operativen Patienten (Blutungsrisiko, Kosten) sind dringend zu empfehlen.

Physical properties of filters for continous renal replacement therapy have a great impact on biocompatibility. According to Poiseuille's law, a filter with more and shorter hollow fibers should offer a decreased pressure drop and, therefore, lower transmembrane pressure (TMP). The aim of this study was to study the effect of a new filter configuration in terms of TMP and clotting compared with the standard configuration.In a prospective randomized cross-over study 2 polysulphone hollow fiber hemofilters, one handmade, which differed only in length and number of hollow fibers were compared. In each group 12 filters were investigated during continous venovenous hemofiltration in patients with acute renal failure due to septic shock. Pressures were measured every 3 hours and running time until filter clotting was documented. Mediators before and after the filter, at the end of treatment and in filtrate were assessed.The standard filter with longer hollow fibers had significantly lower TMPs (106 vs. 194 mmHg, p=0.02) and longer running times (1276 vs. 851 min, p=0.04). There were no differences in hematocrit, total protein, cellular and plasmatic coagulation or blood temperature. No significant elimination of mediators was shown.In contrast to our expectations, the filter with the longer hollow fibers had a better performance, as it ran longer and had lower TMP This may be due to slower blood flow leading to an increase in blood viscosity in a filter with a larger cross section.

Approximately 1-2% of all anesthetized patients are morbidly obese (body mass index35 kg/m2). The perioperative mortality is significantly elevated (up to 20%) compared with lean patients. Morbidly obese patients are at high risk for cardiopulmonary dysfunction. Difficult airway management is reported in 13-20% of obese patients. Hypoxia is often observed due to faster desaturation during induction of anesthesia. After surgery, patients are endangered by a high incidence of obstructive sleep apnea syndrome (50%), pulmonary atelectasis (5%) and acute pulmonary embolism (5-12%).Individualized perioperative management is required based on preoperative history and physical examination. Modern anesthetic drugs (desfluran, sevoflurane or propofol, and remifentanil, respectively) allow rapid recovery and early postoperative mobilization. Adequate monitoring, e.g. by an intraarterial blood pressure monitoring and repetitive blood gas analyses, improves patient safety prior the onset of complications.Postoperative admission on an intensive care unit of morbidly obese patients is based upon concomitant diseases and surgical requirements. The main reason for admission is an inadequate pulmonary gas exchange. This interdisciplinary approach will reduce the risk of anesthesia and avoid complications in morbidly obese patients.

The present study aimed at determining Candida antigen and antibody kinetics during antifungal therapy. 115 non-neutropenic patients with a stay of more than 5 days in an interdisciplinary intensive care unit during a period of 2 years were reviewed. Routinely measured Candida antigen and antibody titers were evaluated at the beginning and during antifungal therapy. In 67 patients serological data were evaluable in defined time slots. Under fluconazole therapy (FT) the median of Candida antigen (Ramco) was 1:4 and did not change significantly. Candida antibody level increased from 1:80 to 1:320. Initial titers between FT and amphotericin B/5-fluorocytosine therapy (AT) showed a significant difference. During AT antigen titers decreased from 1:8 to 1:4 while antibody titers kept constant at a level of 1:160.

Endothelial cells are known to produce reactive oxygen species by several mechanisms. Functional consequences of increased production of reactive oxygen species were investigated in vitro after stimulation with several proinflammatory cytokines. Time dependent increases in DCF-fluorescence as a measure of reactive oxygen load were quantified in single cells after incubation with TNF-alpha, IL-1 and IFN-gamma. The increased DCF-fluorescence was inhibited by cell permeant antioxidative substances Tiron and Tempol. NMMA, an inhibitor of nitric oxide synthase reduced endothelial DCF-fluorescence only marginally, indicating a minor participation of nitric oxide production in this detection system. Cytokine induced endothelial DCF-fluorescence increased in the presence of NADH, whereas coincubation with NADPH or xanthine was without effect. Flavoenzyme inhibitor diphenyliodonium abolished stimulated DCF-fluorescence. Cytokine induced release of MCP-1 and IL-6 by endothelial cells was completely inhibited in the presence of Tiron and Tempol, whereas NMMA was less effective. Collectively these data indicate that cytokine stimulated endothelial cells increase their reactive oxygen species production probably via NADH oxidase and this production may critically be involved in the secretion of MCP-1 and IL-6.

Soon after announcement of the first American ether anesthesias in 1846 one started to anesthetize with ether in Europe. The first ether anesthesia in Germany took place on January 24th, 1947, and was given by Johann Ferdinand Heyfelder in Erlangen. Two weeks later the first ether anesthesia in Berlin was given on February 6th, 1847, by the orthopaedic surgeon Heimann-Wolff Berend. On February 12th, 1847, the surgeon Johann Friedrich Dieffenbach used ether to anesthetize a patient in the Berlin university hospital. Still in 1847 he published his book "The Ether against Pain" which used to be the standard textbook of anesthesia in Germany for many years to come. On February 15th, 1847, Johann Christian Jüngken operated his first patient under ether anesthesia in the surgical department of the Charité hospital assisted by Rudolf Virchow. Since then several famous Berlin surgeons influenced the development of modern anesthesia until the middle of the 20th century. The nitrous oxide bottle was introduced into practice by the Barth company in cooperation with the dentist Carl Sauer and Kurt Schimmelbusch introduced his mask for ether anesthesia. Carl Ludwig Schleich reported at the German congress of surgery in 1894 about his first experience with infiltration anesthesia. Spinal anesthesia developed by August Bier in Kiel was improved during his time in Berlin.

In the present study a method of rapid opiate detoxification under general anaesthesia has been evaluated regarding the safety, the efficacy in preventing withdrawal symptoms, and the long-term results. In addition, it was investigated whether the profile and severity of withdrawal symptoms depend on the type of opiate abused (methadone, heroin, codeine, morphine).Seventy-two opiate addicts were detoxified in an intensive care unit (ICU). Anaesthesia was induced and maintained using propofol infusion. Patients were endotracheally intubated. The opiate receptor antagonist naltrexon was administered into the stomach via a nasogastric tube. Withdrawal symptoms before and after the detoxification treatment were assessed using an objective and a subjective opiate withdrawal scale (OOWS, SOWS). After detoxification patients entered a long-term naltrexone maintenance programme as well as a supportive psychotherapy programme. Vital organ function was monitored using haemodynamic and respiratory parameters as well as body temperature.Organ function parameters were stable during the whole treatment in all patients and no anaesthetic complications were registered. Minor side effects such as bradycardia or hypotension were observed in 20 patients. Compared to patients with pre-existing heroin, codeine, or morphine abuse respectively, patients from the methadone maintenance programme had significantly higher (P0.01) OOWS as well as SOWS values after the treatment. Twelve months after the detoxification 49 patients (68%) were abstinent from opiates whereas 17 patients had relapsed during the period of follow-up. Six patients were lost during follow-up.Rapid opiate detoxification under general anaesthesia is a safe and efficient method to suppress withdrawal symptoms. This treatment may be of benefit in patients who particularly suffer from severe withdrawal symptoms during detoxification and who have failed repeatedly to complete conventional withdrawal. Methadone patients have more withdrawal symptoms than other opiate addicts.

Treatment of opioid addicts by means of competitive opioid receptor antagonists was developed at the University of Vienna in 1987 by Loimer and co-workers. They compared two withdrawal regimens: The short Opiate withdrawal using a staggered naloxone regimen and the rapid opiate detoxification during general anesthesia by means of high doses of naloxone. Based on the latter concept, various modifications have been developed world-wide using either naloxone or as an alternative, naltrexone, an antagonist available for oral administration only. However, there are considerable objections to opioid detoxification during general anasthesia. The main criticism is based an the supposedly unacceptable high risk:benefit-ratio, the higher costs, the lack of psycho-social support, and the lack of prospective studies. However, first results suggest that rapid detoxification procedures are more successful in decreasing relapse than methods which are based on psychiatric treatment alone. As sympathetic hyperfunction is common in rapid detoxification procedures using high doses of opioid receptor antagonists, it is essential to avoid severe autonomic imbalance with possible subsequent impairment of organ functions. To prevent those disturbances, general anesthesia plays an important role. So far, there is almost no information about such methods in the anesthesiological literature. In this article the clinical relevance of such methods is discussed summarizing both the available literature and our own experience and we conclude that rapid opioid detoxification under general anesthesia is a safe and efficient method to suppress withdrawal symptoms. This treatment may be of benefit in patients who particularly suffer from severe withdrawal symptoms and who have failed repeatedly to complete conventional withdrawal.

The social and economical consequences of opiate addiction are a permanently increasing problem within society [1]. To solve drug related problems and to provide effective treatment for these patients represents a considerable challenge. For successful therapy, the physical, as well as the psychological, components of opiate dependancy have to be taken into account [2].

Determination of Functional Residual Capacity (FRC) can be performed through washout methods, indicator gas dilution or bodyplethysmography. Some of these techniques have been adapted for use in intensive care patients whilst being mechanically ventilated. However, most measurement setups are bulky, cumbersome to use and their running costs are high. Hence FRC measurement has not become a routine method in intensive care although it offers considerable advantages in the management of ventilated patients such as the determination of "best PEEP", the detection of progressive alveolar collapse in the course of acute lung injury and during weaning from mechanical ventilation. Up to now most efforts to improve and simplify FRC measurement were made at the expense of accuracy. An ideal method ought to be accurate, easy to handle and cost-effective. It should supply not only FRC data but also information about intrapulmonary gas distribution and dead space. These demands can be met using modern data acquisition software. The pros and cons of all methods available for FRC measurement are discussed in view of their suitability for intensive care patients. A conventional nitrogen washout using emission spectroscopy for measurement of nitrogen concentration gives satisfying exact values for the determination of the parameters mentioned above. The measurement error can be lowered under 5% by special corrections for flow and nitrogen signal (delay and rise times, changes of gas viscosity). For flow measurement a normal pneumotachograph can be used. Using a laptop computer for data acquisition the bed-side monitor fulfills most of the demands in intensive care. It is then also possible to measure indices of intrapulmonary gas distribution such as Alveolar Mixing Efficiency and Lung Clearance Index.

Low selenium plasma levels were often measured in ICU patients with polytrauma, major surgery or various severe diseases. Activation of selenium-dependent functions of the antioxidant metabolism and the immune system is suggested to be causally.In a prospective randomized clinical trial including 24 critically ill patients we investigated the plasma levels of selenium, malondialdehyde, glutathione, elastase, fT3, fT4, TSH, IL-2R, IL-6 and IL-8 with and without parenteral selenium supplementation for 3 weeks (study design: week 1: twice 500 micrograms daily, week 2: once 500 micrograms, week 3: three times 100 micrograms sodium selenite).Following 24 hours of supplementation selenium plasma levels were normalized. Malondialdehyde level decreased in the therapy group significantly beginning at day 3. In the control group we observed increased malondialdehyde values, a disturbed glutathione metabolism and an elevated elastase activity. fT3-values were diminished at day 0 in all patients. In the therapy group we measured a gradual fT3 restoration. In the control group a reactive TSH increase was observed. Selenium supplementation did not lead to an excessive stimulation of IL-2R, IL-6 or IL-8.1. Rapid normalization of selenium plasma levels can be achieved with the applied selenium dosage. 2. Parameters of radical metabolism are significantly reduced following selenium administration. 3. T3 synthesis correlates closely with the selenium levels. 4. Excessive stimulation of the immune system does not appear in the applied dosage.

Ca2+ changes induced by nitric oxide (NO.) were investigated in cultured human endothelial cells. Sodium nitroprusside (SNP) (1-100 mumol/L) and S-Nitroso-N-acetylpenicillamine (SNAP) (100 mumol/L) were used as NO. donors. The cytoplasmatic Ca2+ concentration was calculated using ratiometric FURA2 fluorescence measurements. Both NO. donors caused transient oscillatory Ca2+ changes, which were not detectable in the presence of oxyhemoglobin (50 mumol/L). Digital ratio imaging revealed initiation sites within cells where Ca2+ increases started spreading, which indicates that nonuniformly distributed targets might be involved in these reactions. Calcium was released from intracellular stores as indicated by experiments performed in Ca(2+)-free buffer. L-type Ca(2+)-channel blocker diltiazem (100 mumol/L) was not able to block these responses. NO.-induced Ca2+ release from intracellular stores caused capacitative Ca2+ entry. Both thapsigargin (1 mumol/L) and cyclopiazonic acid (10 mumol/L) inhibited the SNP response completely, whereas neither ryanodine (up to 100 mumol/L) nor dantrolene (100 mumol/L) was able to inhibit Ca2+ changes induced by SNP, indicating that primarily inositol 1,4,5-triphosphate (IP3)-dependent stores are released upon stimulation with NO.. A small inhibitory effect of ATP- and SNP-induced peak [Ca2+]i increase was measured in the presence of both caffeine (20 mmol/L) and procaine (1 mmol/L). Evidence is presented that cGMP is not involved in NO.-induced Ca2+ signals, as neither inhibitors of guanylate cyclase (methylene blue and LY 83583) nor cell permeant analogues of cGMP altered or simulated [Ca2+] changes. An inhibitor of cGMP-dependent protein kinase was also ineffective. We therefore propose that endothelial cells have specific targets proximal or at IP3 receptors to induce Ca2+ changes in endothelial cells stimulated with NO..

Cultured human and rat endothelial cells were used to study cellular toxicity and Ca2+ signalling upon exposure to reactive oxygen species. Superoxide and hydrogen peroxide (O2.-/H2O2) were produced by the hypoxanthine/xanthine oxidase system (HX/XO) and caused intracellular Ca2+ concentration ([Ca2+]i) to rise steadily when activities above 2 mU/ml were used. These Ca2+ increases were also measured when the glucose/glucose oxidase (G/GO) system above 5 mU/ml was used to produce hydrogen peroxide (H2O2). Gross morphological changes appeared to parallel elevated [Ca2+]i levels preceding cell death. However, when HX/XO or G/GO were used at non toxic doses rapid and transient changes in [Ca2+]i were measured. These treatments did not alter subsequent receptor mediated Ca2+ signalling induced by ATP (10 microM) or histamine (100 microM). Superoxide dismutase (50 U/ml), which dismutates O2.- into H2O2 also had no influence, whereas catalase (50 U/ml), which removes H2O2, completely diminished transient [Ca2+]i responses. H2O2 added directly was able to induce similar Ca2+ transients when concentrations of at least 500 microM were used. Buffering trace amounts of iron (o-phenanthroline; 200 microM) in order to inhibit .OH radical formation was not effective to alter Ca2+ changes. Experiments performed in Ca(2+)-free buffer showed a similar rise in [Ca2+]i and readdition of Ca2+ to the extracellular medium indicated the activation of store operated Ca2+ entry. Blocking Ca(2+)-ATPases of the endoplasmatic reticulum with thapsigargin (1 microM) inhibited ROS induced transient increases and cells preincubated with pertussis toxin (200 nM) showed unchanged Ca2+ transients after exposure to both enzyme systems. Phospholipase C inhibitor U73122 (2 microM) effectively reduced hydrogen peroxide induced emptying of intracellular stores. Taken together, we demonstrate that enzymatically produced non-toxic H2O2 rather than O2.- or .OH causes calcium signalling from thapsigargin sensitive stores, and activates store operated Ca2+ entry at least partially by activating phospholipase C. These changes clearly differ from pathological 'oxidative stress' associated with a progressive increase in [Ca2+]i.

In a prospective randomised controlled trial the effect of preoperative normovolaemic haemodilution on coagulation, plasma viscosity and plasma protein levels was examined.50 patients undergoing gastrectomies were investigated (haemodilution group, n = 30; control group, n = 20). In the haemodilution group a haematocrit of 30% was aimed at. Blood was replaced by normovolaemic infusion of 6% hydroxyethyl starch 200/0.5.Haematocrit, colloid osmotic pressure, total serum protein, serum albumin and platelet count were significantly decreased intra- and postoperatively in the haemodilution group compared with control group (p0.01). All of these showed no differences between the two groups on the 7th postoperative day. Global coagulation parameters showed dilutional influences without significant differences between the two groups. Measurements of rheological parameters showed a statistically significant decrease in plasma viscosity in the haemodilution group compared with control group (p0.01). Haemodilution led to a marked reduction in the use of homologous blood (1 unit/haemodilution group; 10 units/ control group). The average volume of 6% hydroxyethyl starch 200/0.5 administered per patient was 15.2 ml/kgKM/d (7.6-22.2 ml/kgKM/d) in the haemodilution group and 12.7 ml/ kgKM/d (8.4-17.7 ml/kgKM/d) in the control group.Haemodilution induced decreases in plasma coagulation, platelet count and plasma proteins did not cause any functional impairement and may just reflect dilution of these parameters. It seems that infusion of 6% hydroxyethyl starch 200/0.5 in an amount of 10-20 ml/kgKM/d does not result in a relevant decrease in coagulation parameters.

Over the last 30 years intensive care medicine has undergone drastic changes not only because of changes in patient population but also because of the progress in medical technology. Given that resources are finite and limited medical and socio-ethical principles should be applied for the distribution and withdrawal of these resources. Scoring systems can not only assist in this decision making process but also provide criteria for the termination of treatment in intensive care. Whilst in intensive care patients should be scored every day to identify as early as possible those patients who are going to die and those who are going to survive in order to use intensive care resources efficiently. After discharge from intensive care quality of life should be an important factor to assess intensive care performance.

We evaluated experimentally (80 Lewis-rats) possible pharmacological strategies in the treatment of intestinal reperfusion injury in hypo- and normothermia. We used a specific perfusion solution containing PGI2 or radical scavengers (superoxide dismutase, oxypurinol, tocopherol, ascorbate). Decreased malondialdehyde (MDA) plasma release after reperfusion proved the antioxidative efficiency of the administered radical scavengers (normothermia-control group: MDA increase after 15 min of reperfusion to 160 +/- 30% compared to level at the end of ischemia, oxypurinol: 110 +/- 23%, tocopherol: 112 +/- 12%, ascorbate: 104 +/- 20%; p0.05). The ATP/ADP-ratio of the therapy groups was stable in contrast to the control group. Alkaline phosphatase release was significantly diminished under radical scavenger administration (normothermia/15 min reperfusion-control group: 7.7 +/- 0.9 mumol/ls, oxypurinol: 4.4 +/- 0.4 mumol/ls, tocopherol: 3.5 +/- 0.1 mumol/ls, ascorbate: 5.9 +/- 0.3 mumol/ls; p0.05). Histologically we observed a mucosa protective effect particularly in the ascorbate group. Other pharmacological strategies are discussed.

With improved technology and development of several mechanical assist devices, the indications of percutaneous transluminal coronary revascularization have been extended. In 39 patients (30 men, mean age = 60.1 +/- 8.1 years) with angina pectoris or heart failure, with poor operative risk-benefit ratio and ejection fraction35% and/or target vessel supplying50% of the viable myocardium, we performed assisted percutaneous transluminal coronary revascularization. Intraortic balloon counterpulsation (n = 16), extracorporal circulation (n = 21), or hemopump (n = 2) were used for mechanical support. Complete 6-week follow up was possible in 27 patients. An improvement of left-ventricular function (patients with EFor = 35% demonstrated an improvement: 27 +/- 7 vs 36 +/- 10%, p0.05), heart failure (patients with EFor = 35% demonstrated an improvement of maximal oxygen uptake: 14 +/- 4 vs 17 +/- 4 ml/kg/min; p0.05) and a marked improvement of angina (23/38 demonstrated CCS-improvement of at least one class) was found. Hospital mortality was as low as 2.6%. Major postinterventional complications included nonfatal myocardial infarction (n = 2), fatal retroperitoneal bleeding (n = 1), pulmonary edema (n = 1), nonfatal ventricular fibrillation (n = 1), cerebrovascular event without residual (n = 1), and deep vein thrombosis (n = 4). In conclusion, assisted percutaneous revascularization was successful in a high risk subset of patients with increased surgical risk and/or poor ventricular function.

We describe a short-time endotoxin-induced rabbit model of hypercoagulability for the study of the coagulation cascade and the therapeutic effects of coagulation inhibitors. Cardiorespiratory function was maintained in rabbits under general anesthesia and standardized mechanical ventilation (tidal volume, 6 ml/kg; 60 breaths/min) via tracheostomy and low-dose inotropic support. Coagulation parameters such as prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen concentration, platelet count, fibrin monomers, D-dimers, antithrombin III and factor XIII activities, thrombelastography, and platelet aggregometry were measured during a 4-h period after sequential double endotoxin administration (80 and 40 micrograms/kg of body weight, intravenously). Mean arterial pressure and arterial and central venous blood gas tensions were monitored. Global clotting, activation parameters of coagulation, and leukocyte count deteriorated significantly in the endotoxin-treated animals but was mainly unaltered in controls (P0.05). Tissue specimens of the lungs, liver, brain, and kidneys were examined. Endotoxin-induced, disseminated fibrin deposition was found in the lungs and liver (P0.01). We conclude that this short-time model of hypercoagulability in rabbits reliably induced disseminated intravascular coagulation. Tracheostomy and mechanical ventilation provided a reproducible model in which the differences between the controls and the endotoxin-treated animals were exclusively due to administration of endotoxin and not to unforeseen complications of the respiratory system. This model allows the study of therapeutic effects of coagulation inhibitors on endotoxin-induced changes.

Liposomes with different charge, size and lipid composition were injected i.v. into pregnant rats and rabbits and their uptake and transport across the placenta were studied. Results show that the placenta is very efficient in removing liposomes from the maternal circulation and that it takes up more liposomes per gram of tissue than the liver. Liposomes are degraded intracellularly in the placenta and the entrapped material is then transported across to the fetus as free molecules. Under the experimental conditions described in this article, no intact liposomes were found to be transported across the placenta. In comparison to the i.v. injection, infusion of liposomes into pregnant rabbits had greater effect on the localization of liposomal drug in the placenta and fetal blood. In summary, these results show that small unilamellar vesicles enhance delivery of drugs and nutrients to the placenta. They also suggest the possible danger of toxicity to the fetus if the expectant female is undergoing liposomal drug treatment.