Generalist palliative care for non-cancer patients : A review article.

BACKGROUND: Most patients in the last phase of life can be treated in the context of generalist palliative care, especially by general practitioners. In contrast to specialized palliative care, non-cancer patients predominate in this setting. OBJECTIVE: The aim of this article is to review the literature and elaborate current topics for non-cancer patients at the end-of-life in primary palliative care. MATERIALS AND METHODS: A literature search was carried out in the databases PubMed and Scopus from 2008 to 2013 followed by a qualitative content analysis according to the PRISMA statement. RESULTS: A total of 127 articles could be included in the qualitative content analysis and the final review whereby four core topics were identified: (1) specific target groups (e. g. elderly patients, patients with advanced heart failure and pain), (2) collaboration of general practitioners with other physicians and health professionals, (3) qualifications in palliative care and (4) provision of primary palliative care. Most articles found were related to the fourth topic and the subtopic of barriers and facilitators of palliative care. Insufficient coordination of the persons involved was a barrier often discussed. Advanced care planning including concrete palliative care aspects at an early stage can be beneficial for both patients and professionals. CONCLUSION: The current literature search highlights the importance of optimizing the processes and structures in providing palliative care and the discussion of end-of-life issues at an early stage in general practice. Therefore, a structured identification of palliative care needs identified by appropriate assessment instruments is crucial.

[Generalist palliative care for non-cancer patients: A review article]. / Hausärztliche Palliativversorgung bei nichtonkologischen Patienten: Eine Übersichtsarbeit.

BACKGROUND: Most patients in the last phase of life can be treated in the context of generalist palliative care, especially by general practitioners. In contrast to specialized palliative care, non-cancer patients predominate in this setting. OBJECTIVE: The aim of this article is to review the literature and elaborate current topics for non-cancer patients at the end of life in primary palliative care. MATERIAL AND METHODS: A literature search was carried out in the databases PubMed and Scopus from 2008 to 2013 followed by a qualitative content analysis according to the PRISMA statement. RESULTS: A total of 127 articles could be included in the qualitative content analysis and the final review whereby four core topics were identified: (1) specific target groups (e.g. elderly patients, patients with advanced heart failure and pain), (2) collaboration of general practitioners with other physicians and health professions, (3) qualifications in palliative care and (4) provision of primary palliative care. Most articles found were related to the fourth topic and the subtopic of barriers and facilitators of palliative care. Insufficient coordination of the persons involved was a barrier often discussed. Advanced care planning including concrete aspects of palliative care at an early stage can be beneficial for both patients and professionals. CONCLUSION: The current literature search elucidates the importance of optimizing the processes and structures in providing palliative care and the discussion of end of life issues at an early stage in general practice. Therefore, a structured identification of palliative care needs identified by appropriate assessment instruments is crucial.

Exploring HIV disease indicators at MDR-TB treatment initiation in South Africa.

BACKGROUND: Understanding relationships between HIV and multidrug-resistant TB (MDR-TB) is crucial for ensuring successful MDR-TB outcomes.METHODS: We used a cross-sectional analysis to evaluate sociodemographic and clinical characteristics as correlates of antiretroviral therapy (ART) use, having an HIV viral load (VL) result, and HIV viral suppression in a cross-sectional sample of people with HIV (PWH) and MDR-TB enrolled in a cluster-randomized trial of nurse case management to improve MDR-TB outcomes.RESULTS: Among 1,479 PWH, the mean age was 37.1 years; 809 (54.7%) were male, and 881 (59.6%) were taking ART. Housing location, employment status, and CD4 count differed significantly between those taking vs. those not taking ART. Among the 881 taking ART, 681 (77.3%) had available HIV VL results. Housing location, CD4 count, and prior history of TB differed significantly between those with and without a VL result. Among the 681 with a VL result, 418 (61.4%) were virally suppressed. Age, education level, CD4 count, TB history, housing location, and ART type differed significantly between those with and without viral suppression.CONCLUSION: PWH presenting for MDR-TB treatment with a history of TB, taking a protease inhibitor, or living in a township may risk poor MDR-TB outcomes.

The prognostic value of IDH mutations and MGMT promoter status in secondary high-grade gliomas.

Reports about the prognostic value of IDH mutations and the promoter region of the O6-Methyl-guanyl-methyl-transferase gene in secondary high-grade gliomas (sHGG) are few in number. We investigated the prognostic value of IDH mutations and methylation of the promoter region of the MGMT gene in 99 patients with sHGG and analyzed the clinical course of those tumors. Patients with sHGG were screened for IDH mutations by direct sequencing, and, for promoter status of MGMT gene, by the methylation-specific polymerase chain reaction. A total of 48 of 99 patients (48.5 %) had secondary anaplastic gliomas (Group 1), while 51 patients had secondary glioblastomas (Group 2). The median survival time after malignant progression of all patients with sHGG and with an IDH mutation was 4 years, which is significantly longer than in patients with wild-type IDH (1.2 years, p = 0.009). Patients' survival was not significantly influenced by the tumors' MGMT promoter status, both in Group 1- 9.7 years vs. 6.1 years, methylated vs. unmethylated promoter (p = 0.330)-as well as in Group 2-1.5 years vs. 1.6 years, methylated versus unmethylated promoter (p = 0.829). In our population, the IDH mutation status was not associated with increased PFS or median survival time in sGBM patients. However, patients with secondary anaplastic glioma and IDH mutation had a significantly improved outcome. In addition, IDH mutations are a more powerful prognostic marker concerning both PFS and MS than the MGMT promoter status in those patients.

Hypoxia induces apelin expression in human adipocytes.

Adipokines play a central role in the development of diseases associated with insulin resistance and obesity. Hypoxia in adipose tissue leads to a dysregulation of the expression of adipokines. The effect of hypoxia on the more recently identified adipokine apelin in human adipocytes is unclear. Therefore, we aimed at investigating the role of hypoxia on the expression of the adipokine apelin. Differentiated human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were cultured under hypoxic conditions for varying time periods. A modular incubator chamber was used to create a hypoxic tissue culture environment (defined as 1% O(2), 94% N, and 5% CO(2)). In addition, hypoxic conditions were mimicked by using CoCl(2). The effect of hypoxia on the expression of the investigated adipokines was measured by real-time PCR and the secretion of apelin was quantified by ELISA. Induction of hypoxia significantly induced mRNA expression of leptin and apelin in differentiated SGBS adipocytes compared with the normoxic control condition. Expression of adiponectin was significantly decreased by hypoxia. In addition, the amount of secreted apelin protein in response to hypoxia was elevated compared to untreated cells. Furthermore, we could demonstrate that the observed hypoxia-induced induction of apelin mRNA expression is in the first phase dependent on HIF-1α. In our study, we could demonstrate for the first time that apelin expression and secretion by human adipocytes are strongly induced under hypoxic conditions and that the early response on hypoxia with apelin induction is dependent on HIF-1α.

Rosette-forming glioneuronal tumor of the fourth ventricle in an elderly patient.

Rosette-forming glioneuronal tumor of the fourth ventricle (RGNT) is a rare condition, which previously has been described predominantly in middle-aged patients. There is limited experience with this kind of tumor in the elderly. Clinical, neuroimaging, and histological features of an example in a 70-year-old male who presented initially with vertigo are detailed and compared with published cases. Neuroimaging studies demonstrated a 4-cm cystic lesion in posterior fossa containing a 1-cm contrast-enhancing nodule on its lateral margin. The lesion was confined to the fourth ventricle and initially thought to be a hemangioblastoma until angiography clarified the minimal tumor vascularization. Gross total resection was achieved. Pathological examination showed a rosette-forming low grade tumor with a cell proliferation rate of 2% being consistent with RGNT. The postoperative course was uneventful and clinical symptoms resolved completely. There was no tumor recurrence after 2 years follow-up. We confirm that the rare and only recently characterized tumor entity of RGNT can also be found in elderly patients; furthermore, it can be associated with a benign course. The main differential diagnosis of RGNT resulting from CNS-imaging modalities in elderly patients are pilocytic astrocytoma and hemangioblastoma of the posterior fossa, which after metastasis are the most common primary adult intra-axial posterior fossa tumors. Therefore, a subtle preoperative radiological diagnosis is warranted and surgery should be performed by experienced hands to avoid neurological deterioration.

[19-year-old asthma patient with pronounced eosinophilia and acute coronary syndrome]. / 19-jähriger Asthmatiker mit ausgeprägter Eosinophilie und akutem Koronarsyndrom.

Diagnosis of Churg-Strauss syndrome should be considered in young asthmatics with fatigue and eosinophilia. On the base of the etiopathology of a 19-year old man, who was initially admitted because of dyspnoea, fever and acute chest pain, we show that eosinophilia gives an important hint for further diagnostic and is the key trend parameter. Histologically an eosinophilic myocarditis could be shown in the myocardial biopsy. High dose prednisolone induced a clear improvement in symptoms, with decrease of the inflammatory signs and the eosinophilia and a clear improvement of the left ventricular function.

Nitrogen-13-labeled nitrite and nitrate: distribution and metabolism after intratracheal administration.

Radioactive nitrogen-13 from nitrite (NO2-) or nitrate (NO3-) administered intratracheally or intravenously without added carrier to mice or rabbits was distributed evenly throughout most organs and tissues regardless of the entry route or the anion administered. Nitrogen-13 from both anions was distributed uniformly between plasma and blood cells. We found rapid in vivo oxidation of NO2- to NO3- at concentrations of 2 to 3 nanomoles per liter in blood. Over 50 percent oxidation within 10 minutes accounted for the similar nitrogen-13 distributions from both parent ions. The oxidation rates were animal species-dependent. No reduction of 13NO3- to 13NO2- was observed. A mechanistic hypothesis invoking oxidation of 13NO2- by a catalase-hydrogen peroxide complex accounts for the results. These results imply a concentration dependence for the in vivo fate of NO2- or nitrogen dioxide.

FKHRL1-mediated expression of Noxa and Bim induces apoptosis via the mitochondria in neuroblastoma cells.

Protein kinase-B (PKB) and its target, the forkhead transcription factor like 1 (FKHRL1)/FoxO3a, have been suggested as regulators of neurotrophin-mediated cell survival in neuronal cells. We analyzed human neuroblastoma cells and found that FKHRL1 was phosphorylated, suggesting its inactivation. To study FKHRL1 function, we infected SH-EP and NB15 cells with a 4OH-tamoxifen-regulated FKHRL1(A3)ER(tm) transgene. Activation of FKHRL1 promoted cytochrome-c release and caspase-dependent apoptosis. FKHRL1 induced TRAIL and the BH3-only proteins Noxa and Bim, implicating both extrinsic and intrinsic death pathways. However, expression of dnFADD did not inhibit FKHRL1-induced cell death, whereas Bcl2 protected against apoptosis. This excluded the death-receptor pathway and suggested that cell death decision is regulated by Bcl2-rheostat. Importantly, RNAi knockdown of Noxa or Bim decreased apoptosis, indicating that Noxa and Bim cooperate to mediate FKHRL1-induced cell death. We conclude that Noxa and Bim establish a connection between FKHRL1 and mitochondria, and that both BH3-only proteins are critically involved in FKHRL1-induced apoptosis in neuroblastoma.

[Teaching emergency medicine at the University Medical Center Freiburg: establishment of an integrative concept]. / Lehrveranstaltung Notfallmedizin am Universitätsklinikum Freiburg : Etablierung eines integrativen Gesamtkonzeptes.

Efforts to improve the quality of undergraduate medical education are commonly hampered by limited human and financial resources. This deficiency may be offset by the development of well structured and innovative teaching concepts, which optimize available assets. The newly conceived modular course "Emergency Medicine" at the University Medical Center Freiburg was conducted for the first time in the winter semester 2006/2007. The core of the course is a 3-day practical training period. It provides the possibility to teach a maximum number of medical students with only four lecturers using patient simulators, interactive case scenarios (simulation software MicroSim), and case scenarios with standardized patients. Evaluation of the course revealed standardized patients to be the best of all teaching methods with an overall average grade of 1.1 (patient simulators 1.2, computer simulation 1.4). Of the students, 88% stated that the practical training encouraged their interest in the speciality emergency medicine. The excellent student evaluation results show that the new course "Emergency Medicine" for medical students constitutes a successful balance between the constraint of resource limitation and the goal of excellent medical education.

Protective role of endogenous carbon monoxide in hepatic microcirculatory dysfunction after hemorrhagic shock in rats.

Maintenance of hepatic microcirculatory flow after ischemia of the liver is essential to prevent hepatic dysfunction. Thus, we determined the differential role of carbon monoxide (CO) and nitric oxide (NO) in the intrinsic control of sinusoidal perfusion, mitochondrial redox state, and bile production in the isolated perfused rat liver after hemorrhagic shock. Administration of tin protoporphyrin-IX (50 microM), a specific inhibitor of the CO generating enzyme heme oxygenase, caused a decrease in sinusoidal flow that was more pronounced after shock compared with sham shock, as determined by in situ epifluorescence microscopy. This was associated with a shift in hepatocellular redox potential to a more reduced state (increased fluorescence intensity of reduced pyridine nucleotides in hepatocytes, decreased acetoacetate/beta-hydroxybutyrate ratio in the perfusate) and a profound reduction in bile flow. In sharp contrast, the preferential inhibitor of the inducible isoform of NO synthase S-methylisothiourea sulfate (100 microM) did not affect sinusoidal flow, hepatic redox state, or function. This indicates that 1.) endogenously generated CO preserves sinusoidal perfusion after hemorrhagic shock, 2.) protection of the hepatic microcirculation by CO may serve to limit shock-induced liver dysfunction, and 3.) in contrast to CO, inducible NO synthase-derived NO is of only minor importance for the intrinsic control of hepatic perfusion and function under these conditions.

Increased polysialic acid neural cell adhesion molecule expression in human hippocampus of heroin addicts.

Chronic exposure to heroin is known to cause cognitive deficits. However, little is known about the underlying molecular mechanisms. It has been suggested that opiate-induced neurotoxicity as well as impaired plasticity and regeneration may be relevant. One of the target regions where regeneration still can be observed in the adult brain is the hippocampus. Since polysialic acid neural cell adhesion molecule is regarded as one of the key players involved in plasticity and regeneration of neural tissue, we analyzed polysialic acid neural cell adhesion molecule expression in the fascia dentate hilus of the human hippocampus of 29 lethally intoxicated heroin addicts and matched controls. Immunohistochemistry with an antibody directed against polysialic acid neural cell adhesion molecule revealed its expression in differently sized cells which could be identified as neurons and glial cells. We observed an increase in the percentage of polysialic acid neural cell adhesion molecule positive neurons in hippocampal hilus of heroin addicts compared with controls (P = 0.001).Interestingly, we also observed polysialic acid neural cell adhesion molecule expression in glial cells as evidenced by double immunofluorescence with glial fibrillary acidic protein and polysialic acid neural cell adhesion molecule using confocal laser scanning microscopy. The fraction of polysialic acid neural cell adhesion molecule positive glial cells was also higher in heroin addicts compared with controls (P = 0.009). In addition, within the group of addicts morphine blood concentrations showed a positive correlation with the percentage of polysialic acid neural cell adhesion molecule positive neurons (P = 0.04; r = 0.547). In conclusion, we observed an increase in polysialic acid neural cell adhesion molecule positive neurons and glial cells in hippocampi of heroin addicts. This might reflect an attempt to repair cell damage due to heroin exposure.

Prognostic Value of Conventional Magnetic Resonance Imaging for Adult Patients with Brain Tumors.

PURPOSE: Magnetic resonance imaging (MRI) is the pivotal diagnostic step in patients with brain tumors, and is performed before histological diagnosis is available. We hypothesized that conventional MRI is as accurate as tumor histology in differentiating malignant from benign clinical course. METHODS: Two neuroradiologists blinded to any clinical information evaluated the first diagnostic MRI of 244 brain tumor patients before any treatment, using a self-developed standardized list of image criteria and prospectively determined world health organization (WHO) tumor grade and tumor entity. All patients were examined with at least T1- and T2-weighted spin echo sequences before and after contrast injection on 1 and 1.5-T MRI scanners. Following the patients prospectively for 8-13 years after diagnosis, we were able to use nonsurvival at 5 years as a criterion for malignity and reference for the prognostic accuracy of both MRI and tumor tissue histology. RESULTS: The accuracy for predicting nonsurvival at 5 years was 91% (95% confidence interval (CI): 87-94%) for MRI and 92% (95% CI: 88-95%) for histology. The Kaplan-Meier survival curves of patients with benign and malignant brain tumors as diagnosed by MRI or histology differed significantly (p < 0.001). Histology confirmed benignity or malignity in 201 patients (82%, 95% CI: 77-87%). Sources of misdiagnosis were metastases diagnosed as astrocytoma WHO IV, atypical meningiomas, and low-grade astrocytoma with malignant transformation. CONCLUSION: MRI appears as accurate as histology in predicting survival at 5 years after diagnosis. Histological diagnosis may be more specific, however, and is needed to assess the tumor's specific biology.

Incidence of pneumonia in mechanically ventilated patients treated with sucralfate or cimetidine as prophylaxis for stress bleeding: bacterial colonization of the stomach.

Retrograde colonization of the oropharynx from the stomach by microaspiration of gastric fluid is a recently recognized phenomenon associated with increased gastric pH that may result in pneumonia during ventilation therapy. In a prospective study we investigated 104 mechanically ventilated patients in the intensive care unit who were receiving sucralfate (n = 49) or cimetidine (n = 55) for stress ulcer prophylaxis. The incidence of pneumonia was 45.5% (25 patients) in the cimetidine group and 26.5% (13 patients) in the sucralfate group (95% confidence interval 0.98 to 6.97; odds ratio 2.61; p = 0.0549). Mortality rates were 18.4% (9 patients) in the sucralfate group versus 25.5% (14 patients) in the cimetidine group (p = 0.48). The mean pH values of gastric aspirates were significantly lower in patients treated with sucralfate than in patients receiving cimetidine (p = 0.044). The number of colony-forming units of Enterobacteriaceae in gastric aspirates was also significantly lower in the sucralfate group (p = 0.0037).

Transgenic mice expressing IFN-gamma in the retina develop inflammation of the eye and photoreceptor loss.

PURPOSE: Inflammatory mediators such as interferon-gamma (IFN-gamma) are thought to play a role in ocular disease. Although IFN-gamma was found in the vitreous of mice with experimentally induced autoimmune uveitis, intracameral injection of this cytokine did not induce intraocular inflammation in mice. Therefore, the authors created a transgenic mouse line using the rhodopsin promoter to direct the expression of IFN-gamma in the photoreceptor cells of the retina. These mice, designated rho gamma, enabled them to model intraocular inflammatory disease. METHODS: The authors fused a 2.1 kb 5' Hind III fragment from the murine rhodopsin gene to the IFN-gamma gene and introduced the DNA construct into fertilized zygotes. These were implanted into pseudopregnant C57BL/6 mice, and the resulting progeny were crossed back to balb/c mice. The transgene was identified by Southern blot hybridization. Eyes from the rho gamma mice were either fixed in zinc formalin and stained with hematoxylin and eosin or were frozen in OCT compound and processed for immunostaining using the indirect immunoperoxidase method with DAB as a chromogen. RESULTS: The rho gamma transgenic mice developed intraocular disease, manifested as intraocular cellular infiltration, loss of photoreceptors, corneal clouding, cataract formation, and epithelial and microglial proliferation. Additionally, rho gamma mice exhibited antigenic changes, comprising GFAP expression on Müller cells, accumulation of neurofilament on photoreceptors, and expression of MHC class I and class II molecules on retinal cells. CONCLUSIONS: IFN-gamma alters the antigenic properties of intraocular tissue and induces intraocular inflammation in mice. The results suggest a key position of IFN-gamma in the development of pathologic conditions related to intraocular inflammation and provide a useful animal model for the further study of inflammatory disorders, including autoimmune diseases.

Application of a new method for analysis of exhaled gas in critically ill patients.

OBJECTIVE: Application of a new method for analysis of exhaled gas in critically ill patients. DESIGN: Open study. SETTING: Surgical intensive care unit of an university hospital. PATIENTS: Thirty-seven consecutive, critically ill, mechanically ventilated patients. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Chemical analysis of the patient's exhaled gas was based upon substance adsorption and concentration onto activated charcoal, microwave desorption and gas chromatographic separation. Patients with acute respiratory distress syndrome (ARDS) exhaled less isoprene than those without ARDS [9.8 (8.2-21.6) vs 21.8 (13.9-41.4) nmol/m2 per min [median (95% confidence interval)], p = 0.04]. In patients who developed pulmonary infection, pentane elimination increased from 0.4 (0.0-5.4) to 2.7 (0.6-6.1, p = 0.05) nmol/m2 per min and isoprene elimination decreased from 5.2 (0-33) to 5.0 (0-17, p = 0.05) nmol/m2 per min, resulting in a significant increase in pentane/isoprene ratio from 0.1 (0-0.3) to 0.4 (0-15, p = 0.007) when compared to patients without pulmonary infection. CONCLUSIONS: The new method allows quantitative analysis of human gas samples with low substance concentrations and is well suited for clinical studies which involve the investigation of metabolic processes in the lung and the body.

Exogenous or endogenous reservoirs of nosocomial Pseudomonas aeruginosa and Staphylococcus aureus infections in a surgical intensive care unit.

OBJECTIVE: A 4 month prospective study was performed to assess the incidence and routes of endogenous or exogenous colonization and nosocomial infection caused by Staphylococcus aureus and Pseudomonas aeruginosa in surgical critically ill patients. DESIGN: A total of 4634 specimens were obtained. Patient's nasal, scalp, and rectal swabs as well as tracheal secretion (TS) were cultured every second day beginning on the day of admission. Nasal swabs and hand cultures of the personnel as well as cultures from gowns were also taken. All isolates of S. aureus were phage typed and 116 of these isolates were also plasmid typed. P. aeruginosa isolates were sero- and pyocin typed. Resistance patterns were determined in all isolates. SETTING: The study was carried out in the surgical intensive care unit (SICU) of an teaching hospital. PATIENTS: During the study period each patient (a total of 153 patients) admitted to the SICU entered the study. RESULTS: P. aeruginosa and S. aureus colonisation rate on admission were 5% and 36.5% respectively. Only 10 patients (6.5%) were colonized with P. aeruginosa during hospitalization, and only 7 patients (4.5%) acquired S. aureus in the surgical intensive care unit (SICU). The most common primary colonisation site of P. aeruginosa was the rectum, whereas S. aureus was predominantly found in nasal cultures. Horizontal transmission of S. aureus occurred in only 2 patients. CONCLUSION: The study suggests that colonisation with P. aeruginosa and S. aureus occurs from endogenous rather than from exogenous sources and that the endogenous acquisition of both bacteria play a more important role in development of nosocomial infections than the exogenous route of transmission.

Influence of architectural design on nosocomial infections in intensive care units--a prospective 2-year analysis.

Nosocomial infection rates in an old intensive care ward constructed in 1924 were compared with those in a new one constructed in 1986. The nosocomial infection rate in the old unit was 34.2% and that in the new unit 31.9%, with an average of 33%. The most frequent infections were: pneumonia, urinary tract infection, septicaemia and wound infection. After transfer of the intensive care unit (ICU) the incidence and profile of nosocomial infections remained the same. These findings suggest that the influence of architectural design has little impact on the incidence of nosocomial infections.

Different effects of early endotoxaemia on hepatic and small intestinal oxygenation in pigs.

OBJECTIVE: Study on simultaneous O2 supply/uptake relationships in liver and gut during endotoxaemia, to determine whether signs of dysoxia develop uniformly in the splanchnic region. DESIGN: Animal study to assess the early effects of endotoxaemia on oxygenation of both liver and small intestine. INTERVENTIONS: Eight anaesthetized pigs received a continuous portal venous infusion of lipopolysaccharide (0.5 microgram.kg-1.h-1) for 6 h. Systemic, pulmonary and splanchnic haemodynamics as well as systemic and splanchnic O2 supply/uptake relationships were determined. RESULTS: There was a multiphasic haemodynamic response pattern characterized by an early (within the 1st h) and a subsequent more prolonged phase (between the 2nd and 6th h) of decreases and recovery of hepatic arterial, portal venous and superior mesenteric arterial blood flows (electromagnetic flow probes) and splanchnic O2 deliveries. Unrelated to perfusion pressure and O2 delivery, there were early and sustained decreases in ileal mucosal surface partial pressure of oxygen (PO2) (multiwire PO2 electrode) and pH (tonometry). This was not reflected by ileal serosal surface PO2, O2 uptake and arteriomesenteric venous pH and partial pressure of carbon dioxide (PCO2) gradients. There was little evidence of concomitant hepatic dysoxia as evaluated by surface PO2. CONCLUSIONS: The study demonstrates early and sustained regional (mucosa) intestinal hypoxia with little evidence of simultaneous hepatic dysoxia during initial endotoxaemia.

Detection of endotracheal tube obstruction by analysis of the expiratory flow signal.

OBJECTIVE: Acute obstruction of endotracheal tubes (ETT) increases airway pressure, decreases tidal volume, increases the risk of dynamic hyperinflation by prolonging the duration of passive expiration, and prevents reliable calculation of tracheal pressure. We propose a computer-assisted method for detecting ETT obstruction during controlled mechanical ventilation. The method only requires measurement of the expiratory flow. DESIGN: Computer simulation; prospective study in two cases; retrospective study in one case and in seven patients with the adult respiratory distress syndrome (ARDS). SETTING: Laboratory of the Section of Experimental Anaesthesiology (University of Freiburg); surgical adult intensive care units in a university hospital (University of Basel) and in a university affiliated hospital (Zentralklinikum Augsburg). PATIENTS: 3 patients with partial ETT or bronchial obstructions and 7 ARDS patients. MEASUREMENTS AND RESULTS: Expiratory flow was measured using a pneumotachograph and integrated to obtain expiratory volume. The time-constant of passive expiration (tauE) as a function of expired volume [tauE(V(E)) function] was calculated from the expiratory volume/flow curve. We investigated the tauE(V(E)) function of data obtained from: (1) computer simulation of mechanically ventilated homogeneous and inhomogeneous lungs intubated with ETTs of different sizes; (2) one patient with an artificial ETT obstruction of 7.5 and 25% of the cross-sectional area of the ETT (case 1); (3) one patient with ETT obstruction due to secretions (case 2); (4) one patient with acute bronchial constriction (case 3); (5) seven ARDS patients who showed an increase in airway resistance of more than 2 cm H2O x s/l. It was found that an ETT obstruction caused an increase in tauE in early expiration (at high flow), whereas tauE in late expiration was virtually unchanged. The reason for this is the flow dependency of the increase in ETT resistance produced by ETT obstruction. Unlike ETT obstruction, an increase in pure airway resistance produced an increase in tauE throughout expiration. CONCLUSIONS: An ETT obstruction can be reliably distinguished from an increase in pure airway resistance by a characteristic pattern change in the tauE(V(E)) function, which can be detected easily even by an automated pattern recognition system.