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Respiratory Effects (respiratory + effects)

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Medical Sciences	60%

Selected Abstracts

PRECLINICAL STUDY: Mechanisms of respiratory insufficiency induced by methadone overdose in rats

ADDICTION BIOLOGY, Issue 1 2010
Lucie Chevillard
ABSTRACT Methadone may cause respiratory depression. We aimed to understand methadone-related effects on ventilation as well as each opioid-receptor (OR) role. We studied the respiratory effects of intraperitoneal methadone at 1.5, 5, and 15 mg/kg (corresponding to 80% of the lethal dose-50%) in rats using arterial blood gases and plethysmography. OR antagonists, including intravenous 10 mg/kg-naloxonazine at 5 minutes (mu-OR antagonist), subcutaneous 30 mg/kg-naloxonazine at 24 hours (mu1-OR antagonist), 3 mg/kg-naltrindole at 45 minutes (delta-OR antagonist) and 5 mg/kg-Nor-binaltorphimine at 6 hours (kappa-OR antagonist) were pre-administered. Plasma concentrations of methadone enantiomers were measured using high-performance liquid chromatography coupled to mass-spectrometry. Methadone dose-dependent inspiratory time (TI) increase tended to be linear. Respiratory depression was observed only at 15 mg/kg and characterized by an increase in expiratory time (TE) resulting in hypoxemia and respiratory acidosis. Intravenous naloxonazine completely reversed all methadone-related effects on ventilation, while subcutaneous naloxonazine reduced its effects on pH (P < 0.05), PaCO2 (P < 0.01) and TE (P < 0.001) but only partially on TI (P < 0.001). Naltrindole reduced methadone-related effects on TE (P < 0.001). Nor-binaltorphimine increased methadone-related effects on pH and PaO2 (P < 0.05) Respiratory effects as a function of plasma R -methadone concentrations showed a decrease in PaO2 (EC50: 1.14 µg/ml) at lower concentrations than those necessary for PaCO2 increase (EC50: 3.35 µg/ml). Similarly, increased TI (EC50: 0.501 µg/ml) was obtained at lower concentrations than those for TE (EC50: 4.83 µg/ml). Methadone-induced hypoxemia is caused by mu-ORs and modulated by kappa-ORs. Additionally, methadone-induced increase in TE is caused by mu1- and delta-opioid receptors while increase in TI is caused by mu-ORs. [source]

Respiratory effects of experimental exposure to office dust

INDOOR AIR, Issue 6 2004
L. Mølhave
First page of article [source]

Respiratory effects of exposure to low levels of concrete dust containing crystalline silica

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 2 2001
E. Meijer MD
Abstract Background Dusts containing crystalline silica are generated in mining, construction, glass, granite and concrete production industries. The association between exposure to low levels of concrete dust containing crystalline silica and reduction in lung function, was evaluated in a cross-sectional study. Methods The study was carried out among 144 concrete workers, from two factories, with exposure assessment of respirable dust and silica by personal samplers. Results of respiratory questionnaires and standardized measurements of lung function were compared with the results in a control population. Multiple linear regression analysis was used in selecting factors that predict (age and standing height standardized residual) lung function. Results The average concentration of respirable dust in both factories was 0.8 mg/m3 and 0.06 mg/m3 for respirable silica. The average silica content of the dust was 9%. The average cumulative dust exposure was 7.0 mg/m3 year and cumulative silica exposure was 0.6 mg/m3 year. Significant associations between exposure to concrete dust and a small lung function (FEV1/FVC ratio, MMEF) loss were found, independent of smoking habits and of a history of allergy. Conclusions Our results indicate that, concrete workers with chronic obstructive pulmonary symptoms and/or work-related lower respiratory symptoms are at risk of having a reduction in lung function (FEV&1/FVC ratio) outside the 5th percentile of the external reference population, and therefore, of mild chronic obstructive pulmonary disease, at respirable concrete dust levels below 1 mg/m3 with a respirable crystalline silica content of 10% (TWA, 8 hr). Am. J. Ind. Med. 40:133,140, 2001. © 2001 Wiley-Liss, Inc. [source]

Respiratory effects on the reproducibility of cardiovascular autonomic parameters

CLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 4 2007
Éva Zöllei
Summary The aim of this study was to assess the influence of breathing pattern on the reproducibility of the most commonly used heart rate and blood pressure variability parameters and baroreflex indices. 5,5 min ECG and blood pressure recordings were made and repeated for 10 healthy volunteers in supine rest on 10 consecutive days during spontaneous and 6 min,1 patterned breathing. We investigated the following parameters: mean RR interval (RRI); the standard deviation of RR intervals (SDRR); the root mean square of successive differences in RRI (RMSSD); the percentage of RRIs which differed by 50% from the proceeding RRI (PNN50); mean systolic arterial pressure (SAP); the standard deviation of SAP (SAP SD); mean mean arterial pressure (MAP); mean diastolic blood pressure (DAP) and baroreflex indices from spontaneous sequence method (upBRS and downBRS) and from cross spectral analysis (LF alpha, HF alpha). To assess reproducibility for each parameter within- and between-subject variability values were calculated and the ratio of within- and between-subject variability was assessed. In addition, we calculated intraclass correlation coefficient (ICC). Compared to spontaneous respiration during 6 min,1 patterned breathing the heart rate and blood pressure variability increased; upBRS, LF alpha and HF alpha increased, downBRS did not change. However, ICC showed good reproducibility for most parameters, which did not improve further with controlled breathing. In conclusion, respiration had a strong influence on the most widely used cardiovascular autonomic parameters. The controlling of breathing did not result in consistent improvement in their reproducibility. [source]

Doppler Superior Vena Cava Flow Evolution and Respiratory Variation in Superior Vena Cava Syndrome

ECHOCARDIOGRAPHY, Issue 4 2008
Fa Qin Lv M.D.
Background: Superior vena cava syndrome (SVCS) is a clinical expression of obstruction of blood flow through the superior vena cava. The patterns of the Doppler flow changes of superior vena cava (SVC), especially the respiratory effects on them have not yet been fully elucidated. This study was to examine SVC Doppler flow patterns and the respiratory effects on them in healthy subjects and patients with SVCS. Methods: The SVC Doppler flow patterns of 18 normal human subjects and 22 patients with SVCS were analyzed at initial diagnosis and were followed up every 2 months for at least 11 months. Results: Among the 22 patients, 5 patients with the tumor near the right atrium oppressing the inferior segment of the SVC had clear VR- and AR-waves, while in the other 17 patients the VR- and AR-waves disappeared or their outlines were vague. The respiratory variations of the S- and D-waves as a percentage change in inspiration compared to expiration in patient group were much lower than those in control group (S-wave: 1.67 ± 3.32% vs. 15.65 ± 16.15%, P = 0.0003; D-wave: 1.80 ± 1.12% vs. 23.55 ± 37%, P = 0.0087), which gradually became larger with treatment and showed no significant difference with those in control group after 7 months. Conclusions: The Doppler flows of the patients with SVCS correlate well with the images of CT scan of them. The respiratory variation of the S- and D-velocities could be used to evaluate the severity of SVC obstruction and its therapeutic effect. [source]

Pulmonary responses of acute exposure to ultrafine iron particles in healthy adult rats

ENVIRONMENTAL TOXICOLOGY, Issue 4 2003
Ya-Mei Zhou
Abstract As critical constituents of ambient particulate matter, transition metals such as iron may play an important role in health outcomes associated with air pollution. The purpose of this study was to determine the respiratory effects of inhaled ultrafine iron particles in rats. Sprague Dawley rats 10,12 weeks of age were exposed by inhalation to iron particles (57 and 90 ,g/m3, respectively) or filtered air (FA) for 6 h/day for 3 days. The median diameter of particles generated was 72 nm. Exposure to iron particles at a concentration of 90 ,g/m3 resulted in a significant decrease in total antioxidant power along with a significant induction in ferritin expression, GST activity, and IL-1, levels in lungs compared with lungs of the FA control or of animals exposed to iron particles at 57 ,g/m3. NF,B,DNA binding activity was elevated 1.3-fold compared with that of control animals following exposure to 90 ,g/m3 of iron, but this change was not statistically significant. We concluded that inhalation of iron particles leads to oxidative stress associated with a proinflammatory response in a dose-dependent manner. The activation of NF,B may be involved in iron-induced respiratory responses, but further studies are merited. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 227,235, 2003. [source]

PRECLINICAL STUDY: Mechanisms of respiratory insufficiency induced by methadone overdose in rats

Opioids and the Management of Chronic Severe Pain in the Elderly: Consensus Statement of an International Expert Panel with Focus on the Six Clinically Most Often Used World Health Organization step III Opioids (Buprenorphine, Fentanyl, Hydromorphone, Methadone, Morphine, Oxycodone)

PAIN PRACTICE, Issue 4 2008
Joseph Pergolizzi MD
,,Abstract Summary of consensus: 1.,The use of opioids in cancer pain:, The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities,including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia,and patient functional status need to be taken carefully into account when addressing pain in the elderly. World Health Organization step III opioids are the mainstay of pain treatment for cancer patients and morphine has been the most commonly used for decades. In general, high level evidence data (Ib or IIb) exist, although many studies have included only few patients. Based on these studies, all opioids are considered effective in cancer pain management (although parts of cancer pain are not or only partially opioid sensitive), but no well-designed specific studies in the elderly cancer patient are available. Of the 2 opioids that are available in transdermal formulation,fentanyl and buprenorphine,fentanyl is the most investigated, but based on the published data both seem to be effective, with low toxicity and good tolerability profiles, especially at low doses. 2.,The use of opioids in noncancer-related pain:, Evidence is growing that opioids are efficacious in noncancer pain (treatment data mostly level Ib or IIb), but need individual dose titration and consideration of the respective tolerability profiles. Again no specific studies in the elderly have been performed, but it can be concluded that opioids have shown efficacy in noncancer pain, which is often due to diseases typical for an elderly population. When it is not clear which drugs and which regimes are superior in terms of maintaining analgesic efficacy, the appropriate drug should be chosen based on safety and tolerability considerations. Evidence-based medicine, which has been incorporated into best clinical practice guidelines, should serve as a foundation for the decision-making processes in patient care; however, in practice, the art of medicine is realized when we individualize care to the patient. This strikes a balance between the evidence-based medicine and anecdotal experience. Factual recommendations and expert opinion both have a value when applying guidelines in clinical practice. 3.,The use of opioids in neuropathic pain:, The role of opioids in neuropathic pain has been under debate in the past but is nowadays more and more accepted; however, higher opioid doses are often needed for neuropathic pain than for nociceptive pain. Most of the treatment data are level II or III, and suggest that incorporation of opioids earlier on might be beneficial. Buprenorphine shows a distinct benefit in improving neuropathic pain symptoms, which is considered a result of its specific pharmacological profile. 4.,The use of opioids in elderly patients with impaired hepatic and renal function:, Functional impairment of excretory organs is common in the elderly, especially with respect to renal function. For all opioids except buprenorphine, half-life of the active drug and metabolites is increased in the elderly and in patients with renal dysfunction. It is, therefore, recommended that,except for buprenorphine,doses be reduced, a longer time interval be used between doses, and creatinine clearance be monitored. Thus, buprenorphine appears to be the top-line choice for opioid treatment in the elderly. 5.,Opioids and respiratory depression:, Respiratory depression is a significant threat for opioid-treated patients with underlying pulmonary condition or receiving concomitant central nervous system (CNS) drugs associated with hypoventilation. Not all opioids show equal effects on respiratory depression: buprenorphine is the only opioid demonstrating a ceiling for respiratory depression when used without other CNS depressants. The different features of opioids regarding respiratory effects should be considered when treating patients at risk for respiratory problems, therefore careful dosing must be maintained. 6.,Opioids and immunosuppression:, Age is related to a gradual decline in the immune system: immunosenescence, which is associated with increased morbidity and mortality from infectious diseases, autoimmune diseases, and cancer, and decreased efficacy of immunotherapy, such as vaccination. The clinical relevance of the immunosuppressant effects of opioids in the elderly is not fully understood, and pain itself may also cause immunosuppression. Providing adequate analgesia can be achieved without significant adverse events, opioids with minimal immunosuppressive characteristics should be used in the elderly. The immunosuppressive effects of most opioids are poorly described and this is one of the problems in assessing true effect of the opioid spectrum, but there is some indication that higher doses of opioids correlate with increased immunosuppressant effects. Taking into consideration all the very limited available evidence from preclinical and clinical work, buprenorphine can be recommended, while morphine and fentanyl cannot. 7.,Safety and tolerability profile of opioids:, The adverse event profile varies greatly between opioids. As the consequences of adverse events in the elderly can be serious, agents should be used that have a good tolerability profile (especially regarding CNS and gastrointestinal effects) and that are as safe as possible in overdose especially regarding effects on respiration. Slow dose titration helps to reduce the incidence of typical initial adverse events such as nausea and vomiting. Sustained release preparations, including transdermal formulations, increase patient compliance.,, [source]

A comparison of the respiratory effects of oxycodone versus morphine: a randomised, double-blind, placebo-controlled investigation,

ANAESTHESIA, Issue 10 2010
S. H. Chang
Summary Oxycodone's respiratory profile (particularly the extent of respiratory depression in comparison to morphine) remains to be fully characterised in the peri-operative period. We randomly assigned ASA 1-2 adults for elective surgery under general anaesthesia to receive saline, morphine 0.1 mg.kg,1, or oxycodone 0.05 mg.kg,1, 0.1 mg.kg,1, or 0.2 mg.kg,1. Results were obtained from six patients in the saline group, 12 patients in the groups receiving morphine 0.1 mg.kg,1, oxycodone 0.05 mg.kg,1 and 0.1 mg.kg,1, and from 10 patients who received oxycodone 0.2 mg.kg,1. Patients were breathing spontaneously and minute ventilation monitored with a wet wedge spirometer for 30 min. All active groups demonstrated significant respiratory depression compared to saline (p < 0.0001 for all groups). The mean (SD) reduction in minute volume from baseline was 22.6% (10.4%) for the morphine 0.1 group and 53.3% (27.2%), 74.4% (12.9%) and 88.6% (13.5%) for the oxycodone 0.05, 0.1 and 0.2 groups, respectively, with significant dose dependent differences between oxycodone groups (p = 0.0007). The extent and speed of onset of oxycodone induced respiratory depression was dose dependent and greater than an equivalent dose of morphine. [source]

Respiratory Effect of Prolonged Electrical Weapon Application on Human Volunteers

ACADEMIC EMERGENCY MEDICINE, Issue 3 2007
Jeffrey D. Ho MD
Background: Conducted electrical weapons (CEWs) are used by law enforcement to subdue combative subjects. Occasionally, subjects will die after a CEW has been used on them. It is theorized that CEWs may contribute to these deaths by impairing respiration. Objectives: To examine the respiratory effects of CEWs. Methods: Human volunteers received a 15-second application of electrical current from a CEW while wearing a respiratory measurement device. Common respiratory parameters were collected before, during, and after exposure. Health histories and demographic information were also collected. Results: Fifty-two subjects were analyzed. Thirty-four underwent a 15-second continuous exposure, and 18 underwent three 5-second burst exposures. In the continuous application group, the baseline mean tidal volume of 1.1 L increased to 1.8 L during application, the baseline end-tidal CO2 level went from 40.5 mm Hg to 37.3 mm Hg after exposure, the baseline end-tidal oxygen level went from 118.7 mm Hg to 121.3 mm Hg after exposure, and the baseline respiratory rate went from 15.9 breaths/min to 16.4 breaths/min after exposure. In the 5-second burst group, the baseline mean tidal volume increased to 1.85 L during application, the baseline end-tidal CO2 level went from 40.9 mm Hg to 39.1 mm Hg after exposure, the baseline end-tidal oxygen level went from 123.1 mm Hg to 127.0 mm Hg after exposure, and the baseline respiratory rate went from 13.8 breaths/min to 14.6 breaths/min after exposure. Conclusions: Prolonged CEW application did not impair respiratory parameters in this population of volunteers. Further study is recommended to validate these findings in other populations. [source]