[Interprofessional symptom management at the end of life]. / Interprofessionelle Symptomkontrolle am Lebensende.

At the end of life patients often show distressful symptoms which significantly reduce their quality of life. The goal of all healthcare professionals should be to recognize the beginning of this end of life period in order to provide good symptom management. For this purpose, existing symptoms have to be recorded, suitable therapeutic goals have to be defined for the current situation and potential therapeutic strategies have to be individually formulated. Besides the identification of underlying causes with the possibility of causal treatment, a symptom-based therapy is often necessary. Therapeutic approaches of different professions should be equally considered and should additionally be used for the benefit of the patient.

[Potential of specialized outpatient palliative care]. / Möglichkeiten der spezialisierten ambulanten Palliativversorgung.

Palliative care patients with incurable advanced disease suffering from complex symptoms can receive specialized outpatient palliative care in addition to the existing ambulatory care system. Qualified physicians and nurses care for patients and their dependents in cooperation with other professionals. In addition to a 24/7 on-call service for emergencies or acute crises, patients and their dependents are offered regular visits.

[Interprofessional symptom management at the end of life]. / Interprofessionelle Symptomkontrolle am Lebensende.

At the end of life patients often show distressful symptoms which significantly reduce their quality of life. The goal of all healthcare professionals should be to recognize the beginning of this end of life period in order to provide good symptom management. For this purpose, existing symptoms have to be recorded, suitable therapeutic goals have to be defined for the current situation and potential therapeutic strategies have to be individually formulated. Besides the identification of underlying causes with the possibility of causal treatment, a symptom-based therapy is often necessary. Therapeutic approaches of different professions should be equally considered and should additionally be used for the benefit of the patient.

[Cancer breakthrough pain. Indications for rapidly effective opioids]. / Tumordurchbruchschmerz. Indikation für schnell wirksame Opioide.

The pharmacotherapy of tumor pain has two main aims: to deliver an adequate basic analgesia using long-term retarded opioid medication and an effective treatment of tumor breakthrough pain using rapidly effective non-retarded opioids. Breakthrough pain is characterized by a sudden onset and rapid increase in the pain level and should be treated with correspondingly rapidly effective opioids. The pharmacological characteristics of previously available and routinely prescribed non-retarded opioids do not always correspond in oral galenics to the demands resulting from the definition of tumor breakthrough pain. As alternatives to these substances five different rapidly effective fentanyl preparations are now available for transmucosal administration.

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.

[Postoperative pulmonary complications: prophylaxis after noncardiac surgery]. / Postoperative pulmonale Komplikationen : Prophylaxe nach nichtkardiochirurgischen Eingriffen.

Postoperative pulmonary complications are a major problem after upper abdominal or thoracoabdominal surgery. They lead to a prolonged ICU stay as well as increased costs and are one of the main causes of early postoperative mortality. Even after uncomplicated operations, postoperative hypoxemia occurs in 30-50% of patients. Acute respiratory failure involves a disturbance in gas exchange. The mortality ranges from 10 to 60% according to the severity of respiratory failure. The most important complications are interstitial and alveolar pulmonary edema, atelectasis, postoperative pneumonia, hypoventilation, and aspiration. Preoperative optimization, postoperative prophylaxis according to a stepwise approach, and early mobilization decrease the rate of complications.

Adenosine-induced cardiac arrest and EEG changes in patients with thoracic aorta endovascular repair.

BACKGROUND: We studied haemodynamic and metabolic variables, and cerebral function after cardiac arrest induced by high dose of adenosine in patients undergoing thoracic aorta endovascular repair. METHODS: Arterial blood pressure, blood gas values and EEG were recorded continuously in 15 patients undergoing anaesthesia (isoflurane) for endovascular thoracic aorta repair. Cardiac arrest was induced by different doses of adenosine (Adrekar, Sanofi-Synthelabo, Berlin, Germany; 0.4-1.8 mg kg(-1) body weight). Serum concentrations of neurone-specific enolase (NSE) were determined before and after stent graft implantation. Neurological function was assessed before and after surgery. RESULTS: After adenosine, the heart beat stopped immediately for 18-58 s in close relation to the adenosine dose. EEG power was significantly reduced to -57%, but reached normal values within 5 min after cardiac arrest. In particular, the fast alpha- and beta-EEG-frequencies sensitively reflected patients' EEG activity during the procedure. No intraoperative increases in NSE concentrations, and no neurological dysfunctions after surgery, were observed. CONCLUSION: After adenosine-induced cardiac arrest, changes in haemodynamic variables and EEG power spectra reversed completely within 1 and 5 min, respectively, without persistent brain dysfunction after stent graft implantation.

Amyloid precursor protein (APP) and its derivatives change after cellular energy depletion. An in vitro-study.

To study the relationship between the metabolism of amyloid precursor protein (APP) and cellular energy failure, HEK 293 cells stably transfected with betaAPP 695 underwent graded energy failure induced either by i) hypoxia (pO(2) 25 mm Hg), ii) inhibition of the respiratory chain by sodium azide (NaN(3)), or iii) by combined glucose deprivation/hypoxia of different duration and severity. Secreted APP (APPs) and the derivative betaA4 were quantified autoradiographically by immunoprecipitation, and [(35)S] methionine labeling. APP holoprotein (APPh) was determined by Western blot analysis. The concentrations of the energy-rich metabolites ATP, ADP, creatine phosphate (CrP), and adenosine were measured by high performance liquid chromatography. Mild to moderate energy failure after NaN(3) treatment (2h, 4h) and hypoxia (2h, 8h) was characterized by normal ATP concentration but also by a high reduction in CrP. A stress condition indicated by an increased ATP turnover and adenosine increase was obtained. Intracellular APPh increased but its metabolites APPs and betaA4 as measured in the extracellular compartment decreased. These changes may point to a compensatory response of APP but also to a initial disturbance in intracellular APP metabolism. Severe abnormalities in both energy formation and utilization after 8h NaN(3) and hypoxia glucose deprivation were found to be accompanied by a drastic fall in intracellular APPh concentration by at least 50%, paralleled by an accelerating reduction in the extracellular concentrations of both APPs and betaA4.A significant linear correlation between APPh and ATP and between CrP and betaA4 became obvious. The data of the present study indicate that abnormalities in APP metabolism were generated in an energy-dependent manner. The obvious similarities to sporadic Alzheimer s disease are discussed.

N-acetylcysteine attenuates the increase in alpha-glutathione S-transferase and circulating ICAM-1 and VCAM-1 after reperfusion in humans undergoing liver transplantation.

BACKGROUND: Oxidative stress and leukocyte-endothelial interactions contribute significantly to the reperfusion injury of the transplanted liver. Therefore, we investigated the effect of N-acetylcysteine (NAC) on reperfusion injury and circulating adhesion molecules during human liver transplantation. METHODS: In a prospective study, 10 orthotopic liver transplantation patients were treated with high-dose NAC and 10 patients were treated with 5% glucose (placebo group) immediately before and during reperfusion of the donor liver. Parameters of hepatocellular injury, cellular oxygenation, plasma cytokines, and circulating adhesion molecules were determined at various time points during the liver transplantation. RESULTS: NAC had no significant effect on the arterial lactate/pyruvate or hydroxybutyrate/acetoacetate ratio during the liver transplantation. At baseline, liver transplantation patients exhibited elevated levels of cytokines and circulating adhesion molecules compared with healthy volunteers (n=7). While no significant effect of NAC on circulating L- and P-selectin was observed, it significantly inhibited the increase in circulating ICAM-1 and VCAM-1 24 hr after reperfusion. There were no significant differences in maximal postoperative values of serum aspartate transaminase (peak AST) or alanine transaminase (peak ALT) between both groups. However, NAC significantly reduced the rise in alpha-glutathione S-transferase after reperfusion of the donor liver. CONCLUSIONS: NAC attenuated the increase in alpha-glutathione S-transferase and circulating ICAM-1 and VCAM-1 after reperfusion of the donor liver, indicating possible cytoprotective effects of NAC.

Neuromodulatory effect of propentofylline on rat brain under acute and long-term hypoperfusion.

1. The effects of propentofylline (PPF, 25 mg kg(-1) body weight per day) on rat cerebral energy state and cytokine expression as well as on behaviour and histopathology were studied after acute and long-term permanent bilateral common carotid artery occlusion (BCCAO). 2. In the absence of PPF, acute ischaemia led to a decrease in energy-rich phosphates in parietotemporal cortex and hippocampus which correlated with an increase in AMP and adenosine concentrations measured by high-performance liquid chromatography technique. The concentrations of cortical cytokines TNF alpha and IL1 beta were increased 12 and 19 fold, respectively. 3. PPF had a neuroprotective action after 20 min of BCCAO, reducing the deleterious effect of acute ischaemia on rat brain energy state and microglial reaction. Simultaneously, PPF treatment increased cyclic-AMP 3 fold. 4. Three weeks of permanent BCCAO did not significantly disturb brain energy metabolism, microglial reaction or histopathology. However, a significant reduction of 30 -- 50% in rat memory capacities and a locomotor hyperactivity were obtained. 5. Continuous PPF-application, however, led to a marked increase in rat working memory and to reduced locomotor activity, which were returned nearly to control levels by 1 week after permanent BCCAO. In summary, PPF showed a clear neuroprotective effect on cerebral energy state and pro-inflammatory cytokines under conditions of acute global ischaemia. Continuous administration of PPF led to memory improvement during permanent BCCAO. 6. These results underscore the benefit of treatment with PPF in clinical practice, particularly during stroke, but also in cerebrovascular and neurodegenerative disorders.

Effect of dopexamine on intestinal tissue concentrations of high-energy phosphates and intestinal release of purine compounds in endotoxemic rats.

OBJECTIVES: To determine the effect of dopexamine, a synthetic catecholamine ligand for dopaminergic and beta2-adrenergic receptors, on intestinal release of adenosine 5'-triphosphate (ATP) degradation products and on intestinal tissue concentrations of high-energy phosphates during endotoxemia. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Twenty-one male Wistar rats. INTERVENTIONS: Rats given endotoxin (Escherichia coli lipopolysaccharide [LPS]; 1.5 mg/kg i.v. over 60 mins) were treated with a continuous infusion of dopexamine (DPX; 2.5 microg/kg/min, n = 7, group LPS + DPX) or 0.9% saline (n = 7, group LPS) during a study period of 120 mins. Animals in the control group (n = 7) received a volume-equivalent infusion of 0.9% saline without endotoxin. MEASUREMENTS AND MAIN RESULTS: In all groups, arterial and portal venous concentrations of adenosine, hypoxanthine, and uric acid were measured at baseline and at 60 and 120 mins after the endotoxin challenge, and we calculated the portal venous/arterial concentration differences as an indicator of the intestinal release of the purine compounds. Furthermore, at the end of the study, the intestinal tissue concentrations of the high-energy phosphates ATP, adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP), creatine phosphate, and adenosine were determined, and we calculated the adenine nucleotide pool, the ATP/ADP and AMP/adenosine ratios, and the adenylate energy charge of the intestinal tissue. Endotoxemia decreases intestinal tissue ATP, ADP, AMP, and creatine phosphate concentrations, increases tissue adenosine content, and increases the release of hypoxanthine and uric acid from the intestinal tract. Dopexamine attenuates the endotoxin-induced decrease of the intestinal tissue adenine nucleotide pool, the AMP/adenosine ratio, and the release of the ATP-degradation products hypoxanthine and uric acid from the intestinal tract. CONCLUSIONS: Normotensive endotoxemia is associated with a deterioration of the intestinal energy balance and an increased release of ATP degradation products, indicating intestinal tissue ischemia. Furthermore, these results suggest the beneficial effects of dopexamine on pathophysiologic alterations of the intestinal energy metabolism during endotoxemia.

[Measurement of local oxygen parameters for detection of cerebral ischemia. The significance of cerebral near-infrared spectroscopy and transconjunctival oxygen partial pressure in carotid surgery]. / Die Messung lokaler Sauerstoffparameter zur Detektion zerebraler Ischämien. Die Wertigkeit der zerebralen O2-Sättigung (NIRS) und des transkonjunktivalen Sauerstoffpartialdrucks in der Karotischirurgie.

UNLABELLED: The principle of, "selective shunting" during carotid endarterectomy requires a special concept to monitor neuronal function. The valence of the oxymetric methods, "near-infrared" spectroscopy (NIRS) and conjunctival oxygen tension (pcjO2) was determined with the reference method somatosensory evoked potentials (SEP). METHODS: In 41 patients undergoing reconstructive surgery on the internal carotid artery, recordings of the different methods were obtained under control, during carotid occlusion and during reperfusion. Cerebral ischemia was assumed if a complete loss of SEP appeared and an intraluminal shunt was placed. Conjunctival oxygen tension was measured continuously and simultaneously on the ipsi- and contralateral eye. RESULTS: In comparison to the reference method (SEP) the sensitivity and specificity of NIRS was 80% and 94%, respectively. The occlusion induced reduction of NIRS appeared 6.5 +/- 3.2 min earlier than the corresponding loss of SEP. Biocular determination of conjunctival oxygen tension was not able to detect hypoperfusion dependent ischemia during carotid occlusion. CONCLUSION: During carotid endarterectomy the measurement of conjunctival oxygen tension is not useful to detect cerebral ischemia. The use of NIRS as a single neuronal monitor is not appropriate to perform, "selective shunting". In contrast to SEP, however, NIRS is characterized by its rapid changes immediately following carotid occlusion. This non invasive method is likely to complete the standard method SEP in a modified monitoring concept of neuronal function during carotid endarterectomy.

Linear relation between cerebral phosphocreatine concentration and memory capacities during permanent brain vessel occlusions in rats.

The present study investigates the interrelation between cerebral energy state and memory capacities in a rat model of stepwise cerebral vessel occlusions. After acute and subchronic permanent vessel occlusions, cortical energy metabolites (ATP, phosphocreatine, ADP, AMP) were detected by high-pressure liquid chromatography (HPLC) analysis, and the effects on learning, memory, and cognitive behavior were evaluated using a hole-board test. The results of the study demonstrated a drastic decrease in energy-rich phosphates by 33% for phosphocreatine and by 44% for ATP after acute vessel occlusions. In addition, rat working and reference memories were strikingly decreased to about 5% of controls. In contrast, two weeks after four-vessel occlusion, the energy state was almost completely restored to control levels. However, a significant decrease in memory capacities was observed in subchronic state. In summary, this study has demonstrated a close linear relationship (p < 0.001) between an impaired cerebral energy state and brain memory dysfunction after acute and permanent cerebral four-vessel occlusion. Thus, this animal model of stepwise reduction of the cerebral blood supply may reflect some clinically relevant processes occurring during cerebrovascular and neurodegenerative diseases.

The neuroprotective effect of cerebral poly(ADP-ribose)polymerase inhibition in a rat model of global ischemia.

In the present study, the effect of poly(ADP-ribose) polymerase (PARP) inhibition on rat cortical energy state was investigated at 24 h after global cerebral ischemia induced by permanent bilateral common carotid artery ligation plus transient hypotension. The specific PARP inhibitor 3-aminobenzamide was injected 10 min before induction of ischemia at a dosage of 5, 10, and 20 mg/kg intracerebroventricularly. Twenty-four hours after ischemia cortical PARP enzyme activity increased from 0.425+/-0.144 to 0.794+/-0.193 units/mg protein. Cerebral ischemia was associated by a decrease in adenosine triphosphate (ATP) and phosphocreatine concentrations to 72.5 and 76.8% of controls, respectively. In addition, an 1.9- and 2. 2-fold increase in adenosine monophosphate and adenosine was observed. Specific PARP inhibition with 10 mg/kg 3-aminobenzamide protected the rat energy state by preserving cortical phosphocreatine and NAD(+). Cortical ATP was not changed significantly after PARP inhibition. In conclusion, activation of the nuclear enzyme PARP plays an important role in cerebral energy metabolism during rat global ischemia. Therefore, specific PARP inhibition may offer new strategies in the therapy of vascular diseases such as stroke.

Permanent cerebral hypoperfusion: 'preconditioning-like' effects on rat energy metabolism towards acute systemic hypotension.

Chronic cerebrovascular disorders are often complicated by additional temporary ischaemic insults, resulting in substantial deterioration of brain energy metabolism. In the present study, chronic limitations of oxygen supply were induced in Wistar rats by 2 weeks of permanent bilateral common carotid artery occlusion (2-vo) to initiate a 'preconditioning-like' effect that protects rat brain energy metabolism against further acute systemic hypotension (15 min). Haemodynamic parameters, arterial blood gases and body temperature were monitored. Energy metabolites were determined in rat parietotemporal cerebral cortex: adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP), phosphocreatine (PCr), and adenosine by the high-pressure liquid chromatography (HPLC) technique and lactate spectrophotometrically. After 2 weeks, permanent 2-vo led to a significant decrease in the concentrations of cortical tissue ATP and PCr, from 3.06+/-0.48 to 2. 09+/-0.28 and from 4.27+/-0.63 to 3.35+/-0.41 micromol/g, respectively. These changes were associated with a two-fold increase in AMP and adenosine. Acute systemic hypotension alone (non-preconditioning) reduced ATP and PCr drastically, to 0.97+/-0. 51 and 1.76+/-1.23 micromol/g. Tissue concentrations of lactate, AMP, and adenosine were markedly increased, three- to five-fold, in 'non-preconditioned' brain tissue. In contrast, after 2 weeks of 2-vo acute hypotension did not significantly alter the cortical energy state any further. The effects of preconditioning on tissue ATP and PCr were most pronounced at 5 min and 48 h after reperfusion. In conclusion, permanent 2-vo seems to activate compensatory mechanisms, which effectively protect the rat's cortical energy metabolism against an additional ischaemic attack ('preconditioning-like' effect).

Ketamine modulates the stimulated adhesion molecule expression on human neutrophils in vitro.

UNLABELLED: Cytokine production, neutrophil adhesion to endothelial cells, and release of reactive oxygen species are thought to be critical events in sepsis or ischemia/reperfusion. Modulation of leukocyte responses by anesthetics may have an important role in limiting tissue injury under these conditions. Therefore, we investigated the effect of ketamine on the expression of CD18, CD62L, and oxygen radical production of human neutrophils in vitro and on interleukin-6 production in endotoxin-stimulated human whole blood. Ketamine inhibited both the N-formyl-methionyl-leucyl-phenylalanine- and phorbol 12-myristate 13-acetate-induced up-regulation of CD18 and shedding of CD62L, determined by flow cytometry, in a concentration-dependent manner. Ketamine also caused a significant suppression of oxygen radical generation of isolated human neutrophils. In addition, there was a significant decrease in endotoxin-stimulated interleukin-6 production in human whole blood. The inhibitory effects were similar for racemic ketamine and its isomers S(+)-ketamine and R(-)-ketamine, suggesting that the inhibition of stimulated neutrophil function is most likely not mediated through specific receptor interactions. IMPLICATIONS: Modulation of leukocyte responses by anesthetics may have an important role in limiting tissue injury in sepsis or ischemia/reperfusion. Therefore, we examined the effect of ketamine on stimulated neutrophil functions in vitro. These neutrophil functions were significantly inhibited by ketamine, independent of whether the racemic mixture or isomers were tested.

[Adenosine-induced heart arrest for endovascular reconstruction of thoracic aneurysms of the aorta]. / Adenosin-induzierter Herzstillstand zur endovaskulären Rekonstruktion von thorakalen Aortenaneurysmen.

INTRODUCTION: Endovascular stent-graft repair is a less invasive technique than traditional open aortic reconstruction for strictly selected patients with descending thoracic aortic aneurysms. To prevent distal migration of the device as a result of the propulsive flow during systole, it is helpful to induce temporary asystole for > or = 20 s while the stent-graft is placed in the thoracic aorta. CASE STUDY: We report here a case study of a patient who was given a bolus dose of 60 mg of adenosine to induce temporary asystole. Placement of the stent-graft was successfully performed during the temporary asystole. After 45 s the patient returned to normal sinus rhythm. He was extubated 4 h after the conclusion of surgery and was discharged after 1 week. CONCLUSION: Induction of temporary asystole with bolus adenosine to facilitate placement of stent-grafts in the thoracic aorta is a simple, easy and effective method of avoiding distal device migration.