The beta-adrenergic receptor agonist, terbutaline, reduces UVB-induced mechanical sensitization in humans.

OBJECTIVES: Previously, we found in cultures of primary neurons and in animals that sensitized primary neurons can be desensitized by treatment with e.g. beta-adrenergic receptor agonists. We now tested whether also in human sensitization such as UVB-radiation induced sunburn-like hyperalgesia can be reduced by intradermal injection of the beta-adrenergic receptor agonist terbutaline. METHODS: In our prospective randomized study, 17 participants received an individual UVB dose to cause a defined local sunburn-like erythema at four locations, two on each forearm. Twenty-four hours later, the sensitized four areas were injected intradermally with terbutaline pH 4.3, terbutaline pH 7.0, saline pH 4.3 or saline pH 7.0, respectively. Pain thresholds were examined before and after induction of UVB-sensitization, and 15, 30 and 60 min after injection of the respective solution. Mechanical pain thresholds of the skin and of deeper tissues were determined by pinprick and pressure algometer measurements, respectively. RESULTS: UVB-irradiation decreased mechanical pain thresholds for pinprick and pressure algometer measurements demonstrating a successful sunburn-like sensitization. Intradermal injection of terbutaline pH 7.0 into the sensitized skin reduced the sensitization for all measured timepoints as determined by pinprick measurements. Pinprick measurements of sensitization were not reduced by injection of terbutaline pH 4.3, saline solution pH 7.0 or saline solution pH 4.3. Also, sensitization of deeper tissue nociceptors were not altered by any of the injections as measured with the pressure algometer. CONCLUSIONS: Similar to our cellular observations, also in humans beta-adrenergic agonists such as terbutaline can reduce the sensitization of primary neurons in the skin. SIGNIFICANCE: We previously showed in model systems that beta-adrenergic stimulation can not only sensitize but also desensitize nociceptors. Our study shows that also in humans beta-adrenergic agonists desensitize if injected into UVB-sensitized skin. This indicates an analgesic activity of adrenergic agonists in addition to their vasoconstrictory function.

[Pneumopericardium due to thorax compression : Overlooked resuscitation injury]. / Pneumoperikard durch Thoraxkompression : Übersehene Reanimationsverletzung.

On postoperative day 15 after right upper lobectomy of a non-small cell lung cancer a 75-year-old patient developed bradycardia followed by asystole during hospitalization on the intensive care unit. After approximately 4 min of chest compressions, circulatory function was re-established but the patient suffered from tachycardia and required continuous vasopressor support. To exclude hypovolemia and assess contractility, transthoracic echocardiography (TTE) was conducted. During the TTE examination neither the intensive care physician nor the cardiologist on call could obtain usable images, which was explained by the lack of experience of both physicians with TTE. Both chest ultrasound and chest x-ray imaging did not reveal any signs of a pneumothorax. A small zone of increased transparency in the cardiac silhouette was not considered to be of pathological relevance. Slowly, the patient recovered. On the following day, a thoracic computed tomography (CT) scan showed an extensive pneumopericardium of the entire pericardium with a seam width of 3 cm. Because of the patient's clinical improvement, a decision for a conservative therapeutic approach was made and 24 h later the seam width was reduced to 2 cm and 9 days later it was no longer detectable. After a total stay of 24 days in the intensive care unit the patient was transferred to a long-term pulmonary care weaning facility. In retrospect, the pneumopericardium as a rare resuscitation injury was the cause for the poor TTE conditions and was overlooked due to a fixation error, because too much attention had been focused only on the detection of a pneumothorax.

[Longitudinal model in pain medicine (LoMoS). Needs assessment and learning developement of learning goals]. / Das longitudinale Modul Schmerzmedizin (LoMoS). Bedarfsanalyse und Lernzielformulierung.

BACKGROUND: Pain medicine as an interdisciplinary, multifaceted field has not yet been assigned the status of a separate medical subject in the curriculum of medical schools in Germany. Pain medicine is often taught by anesthesiologists, neurologists, orthopedic or neurological surgeons either by assignment by the Dean's office or because of their own enthusiasm. In the near future pain medicine as an interdisciplinary course will be mandatory in undergraduate medical education. The authors were interested to investigate the needs and demands of both students and instructors from theoretical and clinical fields in order to develop a longitudinal pain medicine curriculum. METHODS: Based on Kern's curriculum development model, the opinions of students and instructors were investigated: quantitative items were analyzed using Student's t-test for independent variables and heterogenic variance and the content of free text answers was analyzed by forming subsets of similar or identical answers. A concise curriculum was developed. RESULTS: Students from advanced classes noted a bigger discrepancy between the needs formulated and what was actually offered as compared to younger students. Instructors from different theoretical and clinical specialties were unaware of the topics of colleagues from other departments. The analysis of written answers revealed a different understanding of the term pain medicine. CONCLUSION: At the Hannover Medical School, a standardized needs assessment helped to develop LoMoS, the longitudinal pain medicine curriculum, which may also serve as a model for other medical faculties. Students required more practical instruction and teachers were interested in improving networking and discussion among specialists.

Reduction of catheter-related infections in neutropenic patients: a prospective controlled randomized trial using a chlorhexidine and silver sulfadiazine-impregnated central venous catheter.

Antiseptic coating of intravascular catheters may be an effective means of decreasing catheter-related colonization and subsequent infection. The purpose of this study was to assess the efficacy of chlorhexidine and silver sulfadiazine (CH-SS)-impregnated central venous catheters (CVCs) to prevent catheter-related colonization and infection in patients with hematological malignancies who were subjected to intensive chemotherapy and suffered from severe and sustained neutropenia. Proven CVC-related bloodstream infection (BSI) was defined as the isolation of the same species from peripheral blood culture and CVC tip (Maki technique). This randomized, prospective clinical trial was carried out in 106 patients and compared catheter-related colonization and BSI using a CH-SS-impregnated CVC (n=51) to a control arm using a standard uncoated triple-lumen CVC (n=55). Patients were treated for acute leukemia (n=89), non-Hodgkin's lymphoma (n=10), and multiple myeloma (n=7). Study groups were balanced regarding to age, sex, underlying diseases, insertion site, and duration of neutropenia. The CVCs were in situ a mean of 14.3+/-8.2 days (mean+/-SD) in the study group versus 16.6+/-9.7 days in the control arm. Catheter-related colonization was observed less frequently in the study group (five vs nine patients; p=0.035). CVC-related BSI were significantly less frequent in the study group (one vs eight patients; p=0.02). In summary, in patients with severe neutropenia, CH-SS-impregnated CVCs yield a significant antibacterial effect resulting in a significantly lower rate of catheter-related colonization as well as CVC-related BSI.

Lack of toxic side effects in neutrophils following hyperbaric oxygen.

Conflicting data have been reported about the impact of repeated HBO2 exposure on the production of superoxide radicals during the neutrophil respiratory burst (RB) and on phagocytosis. In this study we wanted to see if exposure to hyperoxia would affect human neutrophil RB and phagocytosis. Short- and long-term effects after single or repetitive HBO2 exposure of 2.5 atmospheres absolute over a period of 90 min were studied in 40 healthy volunteers. The RB was measured by the intracellular oxidation of dihydrorhodamine after induction by Escherichia coli (E. coli), or priming with recombinant tumour necrosis factor alpha (TNF-alpha), followed by N-formyl-methionyl-leucyl-phenylalanine (fMLP) stimulation. The phagocytic activity was determined by the intake of FITC-labelled opsonized E. coli. No differences could be found between RB and phagocytic activity before and after HBO2 therapy, regardless of short- or long-term exposure. These findings indicate that exposure to hyperoxia does not impair these two important functions of the human innate host defense.

[Influence of a bolus injection of thiopental and propofol on the expression density of P-selectin and fibrinogen receptors on the surface of human platelets ex vivo]. / Einfluss einer Bolusgabe von Thiopental und Propofol auf die Expressionsdichte von P-Selektin und Fibrinogenrezeptoren auf der Oberfläche humaner Thrombozyten.

OBJECTIVE: Exposure of platelets to anaesthetic agents may alter their functional characteristics and in patients undergoing surgery or long-term sedation this may be clinically relevant. We investigated the influence of thiopentone and propofol on the expression of platelet membrane P-selectin, fibrinogen receptor, and leukocyte-platelet aggregates ex vivo. METHODS: In patients undergoing surgery blood samples were taken from a peripheral vein cannula before induction of anaesthesia with propofol (3.0 mg kg (-1) BW) or thiopentone (7.0 mg kg (-1) BW) and five minutes later (n = 11 in each group). Surface expression of the fibrinogen receptor complex (GP Ib/IIIa), P-selectin, and the percentage of leukocyte-platelet aggregates were measured by flow cytometry after stimulation via the ADP or thrombin receptor pathway. RESULTS: There was no significant difference in the expression of gpIIb/IIIa, P-selectin, and percentage of leukocyte-platelet aggregates in the thiopentone and propofol group after induction of anaesthesia. CONCLUSIONS: In clinically relevant concentrations thiopentone and propofol did not influence the surface expression density of fibrinogen receptors, P-selectin molecules, and the percentage of leukocyte-platelet aggregates ex vivo.

[Effects of Repetitive Exposure to Hyperbaric Oxygen (HBO) on Leukocyte Function]. / Einfluss der hyperbaren Sauerstofftherapie auf die Funktion humaner Leukozyten.

OBJECTIVE: Despite favourable clinical data on the successful use of hyperbaric oxygen (HBO), only limited investigations have been carried out to date regarding the influence of hyperoxia on leukocyte function. In a murine model, CD4+ T-cell population remained unchanged after repeated HBO exposure, however CD8+ cells were found to be increased. The aim of this study was to investigate whether repetitive exposure to hyperoxia would affect human monocyte and lymphocyte function. METHODS: Methods: After Ethics Committee approval the effects of elevated partial oxygen pressure were studied in the course of a ten-day HBO therapy (2.5 atmospheres absolute over a daily period of 90 min). Monocytes and lymphocytes of 30 patients with acute hearing loss were determined by flow cytometry before, throughout and after HBO therapy using monoclonal antibodies to CD3, CD4, CD8, CD14, CD25, CD45 and HLA-DR. Statistical analysis was made by ANOVA (analysis of variance). RESULTS: The relative percentage of CD3+, CD4+, CD8+, CD25+, CD14+, and HLA-DR+ cells remained unchanged during the course of and after HBO therapy. CONCLUSIONS: We conclude that repetitive exposure to hyperoxia does not influence human monocyte and lymphocyte functions in contrast to experimental data.

Effects of colloidal resuscitation fluids on the neutrophil respiratory burst.

BACKGROUND: Experimental studies have revealed that gelatin and HES produce increased neutrophil respiratory burst activity. It was investigated whether 3-percent gelatin (MW 35,000) and three types of 6-percent HES (MW 70,000; degree of substitution, 0.5; 200,000/0.5; 450,000/0.7) preparations can influence superoxide anion production during respiratory burst under clinical conditions. STUDY DESIGN AND METHODS: Blood samples were obtained from 40 patients before and 1 hour after the infusion, before anesthesia and surgical treatment. After stimulation with bacteria (Escherichia coli), the respiratory burst was measured by oxidation of nonfluorescent dihydrorhodamine 123 to the fluorescent rhodamine 123 by the use of flow cytometry. RESULTS: Respiratory burst activity decreased significantly (p = 0.004) from the baseline (60.0 +/- 6.5%) to 1 hour after the administration of the low-molecular-weight HES preparation (55.0 +/- 6.8%). No significant differences in respiratory burst activity could be found after the administration of gelatin or medium-molecular-weight or high- molecular-weight HES solution. CONCLUSION: The investigated administration of gelatin and medium- and high-molecular-weight HES preparations did not influence respiratory burst activity under clinical conditions. However, the neutrophil respiratory burst was impaired after the administration of low-molecular-weight HES. Neutrophil respiratory burst activity may vary according to the type of colloidal plasma substitutes administered.

Efficacy of a benzalkonium chloride-impregnated central venous catheter to prevent catheter-associated infection in cancer patients.

BACKGROUND: This study was performed to determine the efficacy of a benzalkonium chloride-impregnated central venous catheter (CVC) in preventing catheter-related infection in patients suffering from malignant diseases and undergoing chemotherapy. METHODS: A randomized, prospective clinical trial was carried out to compare the incidence of catheter-related colonization and catheter-related bacteremia using an antiseptic-impregnated CVC (n = 25) with that using a standard triple-lumen CVC (n = 25). RESULTS: All patients were treated with intensive chemotherapy for acute leukemia (n = 28), lymphoma (n = 17) or solid tumors (n = 5). Both study groups presented with similar data in regards to age, insertion site, duration of catheterization and neutropenia period during catheterization, demonstrating a comparable risk for catheter-related colonization. Suspicion of infection led to explantation in 14 versus 15 cases. Catheter-related colonization was proven in 4 cases (16%) and catheter-related bacteremia was observed only once (4%) in both groups. Statistical testing showed no significant differences between the study and control group. CONCLUSIONS: The rate of catheter-related colonization was lower than suspected in this high-risk patient group. The use of benzalkonium chloride-impregnated CVC failed to decrease the incidence of catheter-related colonization and bacteremia in patients with a high risk of infectious complications.

Einfluss von Wachstumsfaktoren auf den Respiratory Burst humaner neutrophiler Granulozyten lebertransplantierter Patienten in vitro.

Early post-operative infections remain the most important cause of morbidity and mortality in patients following orthotopic liver transplantation (OLTx). Since polymorphonuclear neutrophils (PMNs) are one of the major determinants of antimicrobial defence, the alteration of their functions may influence the outcome of infection in these patients. Ciclosporin predominantly used as immunosuppressive drug following organ transplantation inhibits superoxide anion production during respiratory burst (RB) of PMNs. Growth factors have been shown to modulate the RB of PMNs in healthy volunteers. It has been examined whether PMNs from patients under immunosuppression following OLTx can be primed by in vitro administration of interleukin-3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF), and granulocyte colony stimulating factor (G-CSF). For flow-cytometric evaluation, leukocytes were obtained as supernatant following sedimentation and were incubated with IL-3 (500 U ml-1), IL-3 and GM-CSF (500 U ml-1), or IL-3 and G-CSF (500 U ml-1). The RB was measured by intracellular oxidation of non-fluorescent dihydrorhodamine to green fluorescent rhodamine after induction of phorbol 12-myristate 13-acetate (PMA) or a combination of tumour necrosis factor alpha (TNF-alpha) and N-formyl-methionyl-leucyl-phenylalanine (FMLP). Following stimulation with PMA, the RB of patients following OLTx could be increased significantly after priming with the combination of IL-3/G-CSF (p < 0.03); following stimulation with TNF-alpha/FMLP the RB could be increased significantly by IL-3 (p < 0.01), IL-3/G-CSF (p < 0.002), and IL-3/GM-CSF (p < 0.002). Regarding the clinical administration of IL-3, GM-CSF and G-CSF following OLTx, the role of these cytokines for prophylaxis or treatment of early postoperative infections should be further investigated.

[Carbon monoxide poisoning]. / Kohlenmonoxidvergiftung.

Carbon monoxide (CO) is a product of incomplete burning of coals and carbon compounds and is a gas without any typical taste, colour or smell. Defective radiators or gas pipes, open fireplaces, fires and explosions are sources of unintended CO production and inhalation. CO bonds with haemoglobin much more readily than oxygen does. CO toxicity causes impaired oxygen delivery and utilisation at cellular level. It affects different sites within the body, but has its most profound impact on the organs with the highest oxygen requirement. CO concentration and the intensity and duration of inhalation determine the extent of intoxication. Following basic life support, assisted or controlled ventilation with 100% oxygen is essential during emergency care. Hyperbaric oxygenation (HBO) is the preferred therapeutic option for releasing CO from its binding to haemoglobin. It has been shown that CO may cause lipid peroxidation and leukocyte-mediated inflammatory changes in the brain, a process that may be inhibited by HBO. Patients with neurological symptoms including loss of consciousness and expectant mothers should undergo HBO treatment, no matter how high their CO levels are. Neonates and in-utero fetuses are more vulnerable due to the natural leftward shift of the dissociation curve of fetal haemoglobin, a lower baseline pO2 and carboxyhaemoglobin levels at equilibration that are 10-15% higher than maternal levels. Physicians need to be aware of the potential occurrence of this life threatening hazard so that appropriate emergency treatment can be administered and fatalities prevented.

Anaesthesiological and criterial care aspects regarding the treatment of patients with arteriovenous malformations in interventional neuroradiology.

In recent years, the neuroradiological treatment of cerebral and spinal arteriovenous malformations (AVMs) has undergone significant evolution and improvement. Endovascular embolisation procedures of AVMs are mainly performed under general anaesthesia. Different pathophysiological characteristics of patients with AMVs must be considered for the choice of the anaesthetic procedures. Anaesthesiological management must aim at maintaining stable intracranial haemodynamics; thus, the drugs used must be evaluated according to their effects on brain perfusion, brain metabolism, and intracranial pressure. Rapid recovery to normal central nervous functions should be obtained postoperatively. Close-meshed neurological surveillance should be exercised in order to detect immediately any alteration of neurological state. In summary, anaesthesiological management of interventional neuroradiology is based on the same well-established principles as anaesthesia in neurosurgery.

Tracheal injury as a sequence of multiple attempts of endotracheal intubation in the course of a preclinical cardiopulmonary resuscitation.

Management of the difficult airway requires an appropriate approach based on personal clinical experiences. For every physician involved in rescue and emergency medicine, it is important to know the difficult airway algorithm and be familiar with alternative techniques of managing the difficult airway. We report a case of tracheal injury caused by multiple attempts at intubating the trachea. Based on current knowledge, apart from surgical equipment for cricothyroidotomy the laryngeal mask airway (LMA) and the Combitube (ETC) should be available on any ambulance vehicle staffed by an emergency physician. In future, blind intubation through the intubating laryngeal mask airway (ILMA) could offer a new opportunity.