Effect of aspirin dose on gastrointestinal permeability.

The primary purpose of this study was to determine the aspirin dose that increases gastrointestinal (GI) permeability. A pilot study was also conducted to determine whether the menstrual cycle affects GI permeability. Both portions of the study involved 4 experimental conditions. For the aspirin portion, 8 subjects ingested 0 mg, 325 mg, 650 mg, or 975 mg of aspirin the night before and the morning of an experiment. For the menstrual cycle pilot study, 5 female subjects with regular menstrual cycles were tested for GI permeability on the same day each week for 4 weeks. GI permeability was assessed by the urinary excretion of ingested probes. Sucrose (5 g) was used to determine gastroduodenal permeability. Lactulose (5 g) and rhamnose (2 g) were used to assess small intestinal permeability via the lactulose-to-rhamnose urinary excretion ratio (L/R). The data indicated that the menstrual cycle had no effect on GI permeability. In contrast, gastroduodenal permeability was significantly (P <0.008) increased following a dose of 650 mg aspirin and small intestinal permeability (L/R) was significantly (P <0.008) increased following a dose of 975 mg aspirin. These results suggest healthy individuals should be cautious even with acute aspirin use as it may result in GI barrier dysfunction.

[Fostering organ donation in the intensive care unit : A best practice example]. / Förderung der Organspende auf der Intensivstation : Ein Best-Practice-Beispiel.

We report on the development and implementation of a bundle of measures with which we increased the number of post-mortem organ donations performed in our hospital from 2 per year to 10 per year within 5 years.

Visualization of the structure of native human pulmonary mucus.

Human respiratory mucus lining the airway epithelium forms a challenging barrier to inhalation therapeutics. Therefore, structural elucidation of hydrated mucus is essential for an efficient drug delivery development. The structure of mucus has been primarily investigated by conventional electron microscopy techniques, which operate under vacuum conditions and require sample preparation steps that might alter the structure of mucus. In this study we investigated the impact of dehydration on mucus and analyzed the structure of mucus in its hydrated state. Cryo-scanning electron microscopy (Cryo-SEM) analysis of mucus showed, that during the process of sublimation, non-porous structure of mucus is transformed into a porous network. Similarly, images acquired by environmental scanning electron microscopy (ESEM), revealed a non-porous structure of hydrated mucus, while further observation at decreasing pressure demonstrated the strong influence of dehydration on mucus structure. We could successfully visualize the structural organization of the major gel forming mucin MUC5B in its hydrated state by employing stimulated emission depletion (STED) microscopy, which allowed resolving the nano-scale patterns of mucin macromolecules within the essentially pore-free mucus structure. The general structural organization of mucus components was addressed by confocal laser scanning microscopy (CLSM), which revealed the heterogeneous and composite structure of mucus. These results provide a novel view on the native structure of mucus and will affect drug delivery development.

Lung perfusion affects preload assessment and lung water calculation with the transpulmonary double indicator method.

OBJECTIVES: The transpulmonary double indicator method uses intra- and extravascular indicators to calculate cardiac output, intrathoracic blood volume, global end-diastolic volume, and extravascular lung water content. Since lung perfusion may be of importance during these measurements, we studied the effects of pulmonary blood flow occlusion on measurements obtained with this method. SETTING: Experimental animal facility of a University department. METHODS AND INTERVENTIONS: In seven pigs, the branch of the pulmonary artery perfusing the lower and middle lobe of the right lung was occluded. Measurements before, during, and after the occlusion were made with a pulmonary artery catheter and a commonly used transpulmonary double indicator catheter and device. MEASUREMENTS AND RESULTS: Occlusion of the right lower and middle lobe branch of the pulmonary artery increased mean pulmonary pressure (before occlusion: 24+/-1, during occlusion: 32+/-2, after reopening 25+/-1 mmHg; P<0.05), increased right ventricular end-diastolic volume (172+/-34, 209+/-21, 174+/-32 ml, respectively; P<0.05), decreased intrathoracic blood volume (998+/-39, 894+/-48, 1006+/-49 ml, respectively; P<0.05), and decreased extravascular lung water (7.2+/-0.5, 4.2+/-0.4, 6.9+/-0.4 ml/kg, respectively; P<0.05) without causing significant changes in cardiac output. All changes were reversible upon reopening the vessel. CONCLUSIONS: These data show that the transpulmonary double indicator method may underestimate extravascular lung water and right ventricular preload when the perfusion to parts of the lung is obstructed.

Immunoassays based on electrochemical detection using microelectrode arrays.

We show that CombiMatrix's VLSI arrays of individually addressable electrodes, using conventional CMOS integrated circuitry, can be used in detecting various analytes via immunoassay protocols. These microarrays provide over 1000 electrodes per square centimeter. The chips are coated with a porous material on which specific affinity tags are synthesized proximate to selected electrode sites. CombiMatrix microarrays are used to develop spatially multiplexed assay formats for biological entities over a wide range of sizes, from small molecules to cells. Antibodies are tagged with coded affinity labels and then allowed to self-assemble on the appropriate electrode assay sites. Each analyte-specific antibody is chaperoned to individual, predetermined locations by the self-assembly process. The resulting chip can perform numerous different analyte-specific immunoassays, simultaneously. We present new detection technologies based upon the use of the active individually addressable microelectrodes on the chip: redox enzyme amplified electrochemical detection. The results for human alpha1 acid glycoprotein, ricin, M13 phage, Bacillus globigii spores, and fluorescein indicate that this method is one of the most sensitive available, with limits of detection in the attomole range. The detection range is 4-5 logs of analyte concentration, with an assay volume of 50 microl or less. The system provides for a host of multiplexed immunoassays because of the large number of electrodes available. We show how the assays can be optimized for maximum performance on the CombiMatrix microarray platform.

[Supraglottic airway devices]. / Supraglottische Atemwegshilfen.

All guidelines and algorithms for the management of difficult airways include the use of supraglottic airway devices. This report provides information on the different types of these devices and gives selection criteria for different scenarios.

Effects of arginine vasopressin on oxygenation and haemodynamics during one-lung ventilation in an animal model.

In a case of arterial hypotension during one-lung ventilation, haemodynamic support may be required to maintain adequate mean arterial pressure. Arginine vasopressin, a potent systemic vasoconstrictor with limited effects on the pulmonary artery pressure, has not been studied in this setting. Twelve female pigs were anaesthetised and ventilated and arterial, central venous and pulmonary artery catheters were inserted. A left-sided double lumen tube was placed via tracheostomy and one-lung ventilation was initiated. The animals were in the left lateral position, with the left lung ventilated and right lung collapsed. Respiratory and haemodynamic values were recorded before and during a continuous infusion of arginine vasopressin sufficient to double the mean arterial pressure. The arginine vasopressin caused a decrease in cardiac output (3.8+/-1.1 vs. 2.7+/-0.7 l/min, P <0.001) and mixed-venous oxygen tension (39.1+/-5.8 vs. 34.4+/-5 mmHg, P=0.003). Pulmonary artery pressure was unchanged (24+/-2 vs. 24+/-3 mmHg, P=0.682). There was no effect of the arginine vasopressin on arterial oxygen tension (226+/-106 vs. 231+/-118 mmHg, P=0.745). However, there was a significant decrease in shunt fraction (28.3+/-6.2 vs. 24.3+/-7.8%, P=0.043) and a significant proportional increase in perfusion of the ventilated lung (78.8+/-9.5 vs. 85.5+/-7.9%, P=0.036). In our animal model of one-lung ventilation, doubling mean arterial pressure by infusion of arginine vasopressin significantly affected global haemodynamics, but had no influence on systemic arterial oxygen tension.

[Preclinical transtracheal emergency ventilation. Animal experimental comparison of two techniques]. / Präklinische transtracheale Notfallventilation. Tierexperimenteller Vergleich zweier Techniken.

INTRODUCTION: Prehospital transtracheal ventilation via a needle cricothyroidotomy may be lifesaving in cannot-intubate-cannot-ventilate situations. A self-made device consisting of a three-way stopcock placed between a transtracheal airway catheter and an oxygen supply was constructed and the effectiveness of the device was compared with a hand-triggered emergency jet generator in animal experiments. MATERIALS AND METHODS: An emergency transtracheal airway catheter was inserted into the trachea of 10 anesthetized pigs (18-35 kgbw) and a situation of partial expiratory airway obstruction was established. All pigs were ventilated in a randomized order via the transtracheal airway catheter with the hand-triggered emergency jet injector and the self-made device for 15 min each. RESULTS: With both devices satisfactory oxygenation and ventilation was achieved in all animals. CONCLUSIONS: The efficacy of the self-made device during the experiment was comparable with the efficacy of the hand-triggered emergency jet injector.

Pretreatment with sufentanil reduces myoclonus after etomidate.

BACKGROUND: Myoclonic movements are a common problem during the induction of general anesthesia with etomidate. We investigated the influence of pretreatment with the opioid sufentanil on the incidence of etomidate-induced myoclonus. METHODS: Forty female patients (ASA physical status I-III) were randomly assigned to receive double-blinded either 0.3 micro g kg-1 of sufentanil or placebo 150 s before the induction of sleep with 0.3 mg kg-1 of etomidate. The patients were observed for any myoclonic movement. Grade of dizziness, breathing frequency, non-invasive blood pressure and heart rate were measured during the study period. RESULTS: None of the 20 patients receiving sufentanil had myoclonic movements after the administration of etomidate, whereas 16 patients in the placebo group (80%) experienced such movements (P<0.01). No cases of apnoea before induction of sleep were seen in the sufentanil group. CONCLUSION: Sufentanil 0.3 micro g kg-1 is an effective and safe drug to reduce myoclonus after etomidate without causing any harmful side-effect.

[Transtracheal oxygenation in respiratory tract obstruction from a hypopharyngeal tumor]. / Transtracheale Oxygenierung bei Atemwegsverlegung durch einen Hypopharynxtumor.

A 42-year-old male with a history of chronic alcoholism was admitted to the department of otolaryngology with acute respiratory insufficiency and generalised cyanosis due to a respiratory obstruction by a large tumour of the hypopharynx. Because of the size and location of the tumour and the risk of bleeding, orotracheal intubation by direct laryngoscopy was considered almost impossible. To improve oxygenation cricothyroidal punction and oxygen insufflation was done immediately and SpO2 increased from 56% to 82%. Awake fiberoptic nasotracheal intubation was performed under topical anaesthesia, then general anaesthesia was induced and controlled ventilation was started. After surgical tracheotomy the patient was transferred to an intensive care unit and 12 h later the patient was discharged from the ICU.

Midazolam pretreatment reduces etomidate-induced myoclonic movements.

During induction of anaesthesia with etomidate, myoclonic muscle movements are frequent. In this study, pretreatment with a small dosage of etomidate or midazolam was compared with placebo for the prevention of myoclonic muscle movements. Sixty patients, premedicated with oral midazolam, were pretreated in a randomized double-blinded fashion with etomidate 0.05 mg/kg i.v., midazolam 0.015 mg/kg i.v. or normal saline i.v. (placebo) in three groups of 20 patients each. The pretreatment was followed after 90 seconds by etomidate 0.3 mg/kg i.v. One minute after onset of hypnosis, induction of anaesthesia was completed with sufentanil and rocuronium. From the time of pretreatment to completion of anaesthesia, patients were observed for myoclonic muscle movements by a single physician, blinded to group allocation. Myoclonic movements were graded on a scale of 0 to 3. The incidence of myoclonic movements was significantly lower in patients pretreated with midazolam (4 of 20) compared with placebo (18/20) (P < 0.01). Midazolam 0.015 mg/kg i.v., administered 90 seconds before induction of anaesthesia with etomidate, is effective in reducing etomidate-induced myoclonic muscle movements.

[Urapidil for treatment of postanesthetic shivering following general anesthesia. A placebo controlled pilot study]. / Urapidil zur Therapie von postanästhetischem Shivering nach Allgemeinanästhesie. Eine placebokontrollierte Pilotstudie.

OBJECTIVE: Postanaesthetic shivering is common during recovery from general anaesthesia. Therefore we studied whether urapidil suppresses postanaesthetic shivering. METHODS: With written informed consent and approval of the local ethics committee, patients (ASA I-II) recovering from general anaesthesia were monitored for 1 h. Patients with continuous shivering for a period of 5 min were randomly treated either with 5 ml placebo (isotonic saline) or 25 mg urapidil in a double-blind trial. This treatment procedure was repeated if shivering did not stop. A complete suppression of shivering was appraised as a sufficient treatment. RESULTS: Shivering occurred in 20 of the patients studied and urapidil stopped shivering in 7 out of the 10 treated patients, whereas the placebo stopped shivering in only 2 out of 10 patients (P < 0.05). CONCLUSION: In a placebo controlled trial, it was demonstrated that postanaesthetic shivering can be successfully treated by urapidil in 70% of the patients.

A comparison between meperidine, clonidine and urapidil in the treatment of postanesthetic shivering.

UNLABELLED: Postanesthetic shivering can be treated with many types of drugs. We compared the effects of meperidine, clonidine, and urapidil on postanesthetic shivering. Sixty patients shivering during recovery from general anesthesia were treated in a randomized, double-blinded fashion with 25 mg meperidine IV, 0.15 mg clonidine IV, or 25 mg urapidil IV in three separate groups of 20 patients each. If shivering did not stop within 5 min, the treatment was repeated once; clonidine was replaced with saline for the second dose. Rectal temperature, arterial blood pressure, heart rate, SaO(2) and vigilance were monitored. Clonidine stopped shivering in all 20 patients. A single dose of meperidine stopped the shivering in 18 of 20 patients, with the other 2 patients needing a second dose. Urapidil was less effective: the first dose stopped the shivering in only six patients; the second dose was effective in another six; the drug was ineffective in 8 of 20 patients. Meperidine and clonidine were both nearly 100% effective in treating postanesthetic shivering without negative side effects. By comparison, urapidil was only effective in 60% of patients treated (P <0.01). IMPLICATIONS: Patients shivering during recovery from general anesthesia were treated in a randomized double-blinded fashion with meperidine, clonidine, or urapidil. Meperidine and clonidine were both very effective, whereas urapidil was only effective in 60% of patients treated.

The effects of increasing concentrations of isoflurane and desflurane on pulmonary perfusion and systemic oxygenation during one-lung ventilation in pigs.

UNLABELLED: During one-lung ventilation (OLV), hypoxic pulmonary vasoconstriction (HPV) reduces venous admixture and attenuates the decrease in arterial oxygen tension by diverting blood from the nonventilated lung to the ventilated lung. In vitro, desflurane and isoflurane depress HPV in a dose-dependent manner. Accordingly, we studied the effects of increasing concentrations of desflurane and isoflurane on pulmonary perfusion, shunt fraction, and PaO(2) during OLV in vivo. Fourteen pigs (30-42 kg) were anesthetized, tracheally intubated, and mechanically ventilated. After placement of femoral arterial and thermodilution pulmonary artery catheters, a left-sided double-lumen tube (DLT) was placed via tracheotomy. After DLT placement, FIO(2) was adjusted at 0.8 and anesthesia was continued in random order with 3 concentrations (0.5, 1.0, and 1.5 minimal alveolar concentrations) of either desflurane or isoflurane. Differential lung perfusion was measured with colored microspheres. All measurements were made after stabilization at each concentration. Whereas mixed venous PO(2), mean arterial pressure, cardiac output, nonventilated lung perfusion, and shunt fraction decreased in a dose-dependent manner, PaO(2) remained unchanged with increasing concentrations of desflurane and isoflurane during OLV. In conclusion, increasing concentration of desflurane and isoflurane did not impair oxygenation during OLV in pigs. IMPLICATIONS: In an animal model of one-lung ventilation, increasing concentrations of desflurane and isoflurane dose-dependently decreased shunt fraction and perfusion of the nonventilated lung and did not impair oxygenation. The decreases in shunt fraction are likely the result of anesthetic-induced marked decreases in cardiac output and mixed venous saturation.

Oxygenation during one-lung ventilation: the effects of inhaled nitric oxide and increasing levels of inspired fraction of oxygen.

UNLABELLED: We studied whether inhaled nitric oxide (NO) would improve arterial oxygen tension (PaO(2)) and reduce the occurrence of oxygen saturation of hemoglobin (O(2)Hb) < 90% during one-lung ventilation (OLV). One-hundred-fifty-two patients were ventilated either with or without NO (20 ppm) with an inspired fraction of oxygen (FIO(2)) of either 0.3, 0.5, or 1.0 during OLV. Anesthesia was induced and maintained with propofol, remifentanil, and rocuronium IV, and lung separation was achieved with a double-lumen tube. During OLV, we set positive end-expiratory pressure at 5 cm H(2)O, peak pressure at 30 cm H(2)O, and end-tidal CO(2) at 30 mm Hg. The nonventilated lung was opened to room air and collapsed. During OLV, three consecutive measurements were performed every 10 min. The operated lung was temporarily ventilated if pulse oximetric saturation (SpO(2)) decreased to < 91%. SpO(2) <9 1% occurred in 2 of the 152 patients. SpO(2) overestimated O(2)Hb by 2.9% +/- 0.1%. NO failed to improve oxygenation or alter occurrence of O(2)Hb < 90% during OLV across all time points and all levels of FIO(2). Increasing FIO(2) increased oxygenation and decreased occurrence of O(2)Hb < 90% (P: < 0.001). At FIO(2) = 1, PaO(2) was higher (P < 0.01) and O(2)Hb < 90% rate tended to be lower (P = 0.1) during right versus left lung ventilation. PaO(2) was higher in patients undergoing pneumonectomy and lobectomy than in those undergoing metastasectomy or video-assisted operations (P < 0.05). IMPLICATIONS: Inhaled nitric oxide failed to improve oxygenation during one-lung ventilation. Oxygenation during one-lung ventilation was improved with increasing levels of FIO(2) during ventilation of the right versus the left lung and with increasing pathology of the nonventilated lung.