Irvin Mayers

Tiotropium in Combination with Placebo, Salmeterol, or Fluticasone–Salmeterol for Treatment of Chronic Obstructive Pulmonary Disease: A Randomized Trial

Context Physicians use multiple medications to treat chronic obstructive pulmonary disease (COPD). Contribution In this multicenter trial, 449 adults with moderate or severe COPD were randomly assigned to receive tiotropium and placebo, tiotropium and salmeterol, or tiotropium and fluticasonesalmeterol for 1 year. About 63%, 65%, and 60% of patients, respectively, had exacerbations. The third group, but not the second group, had better lung function and fewer hospitalizations than the first group. Caution Many patients discontinued assigned medications. Implications Adding fluticasonesalmeterol to tiotropium may improve lung function and decrease hospitalizations, but it does not affect reduce exacerbations in patients with moderate or severe COPD. The Editors Most patients with moderate or severe chronic obstructive pulmonary disease (COPD) experience chronic progressive dyspnea that is not alleviated by short-acting bronchodilators. It is therefore not surprising that many patients are treated with multiple inhaled medications to optimize their lung function and minimize symptoms (1). Published guidelines on COPD state that the goals of pharmacologic therapy should be to control symptoms, improve health status, and reduce the frequency of COPD exacerbations (2, 3), and many published guidelines advocate combining different classes of long-acting bronchodilators or inhaled steroids to achieve these goals (2, 3). In the past several years, several studies have shown that treatment of COPD with the long-acting anticholinergic tiotropium (47); the long-acting 2-agonist salmeterol (810); or products that combine inhaled steroids and long-acting 2-agonists, such as fluticasonesalmeterol or budesonideformoterol (1114), improve dyspnea and quality of life and decrease exacerbation rates compared with placebo. However, no studies have assessed whether therapy with a combination of these products provides greater clinical benefit than does therapy with these agents used alone. 2-Agonists and anticholinergics work by different mechanisms to cause bronchodilation (15), and inhaled corticosteroids may have an anti-inflammatory effect in COPD (16). Thus, it makes theoretical and intuitive sense that combining these therapies might be more beneficial than therapy with 1 agent alone. However, safety concerns, such as side effects associated with long-term use of long-acting 2-agonists and inhaled corticosteroids, and economic issues related to the additional costs of these medications may argue against routine use of inhaled medication polypharmacy without evidence of efficacy. We therefore conducted a randomized, double-blind, placebo-controlled clinical trial to determine whether combining tiotropium with salmeterol or fluticasonesalmeterol produces greater improvements in clinical outcomes for adults with moderate or severe COPD compared with tiotropium therapy alone. Methods Design We designed a parallel-group, 3-group, randomized, double-blind, placebo-controlled trial in patients with moderate or severe COPD that was conducted from October 2003 to January 2006. The study protocol has been published elsewhere (17). The research ethics boards of all participating centers approved the study, and all trial participants provided written informed consent. Setting and Participants We enrolled patients with diagnosed moderate or severe COPD from 27 Canadian medical centers. Twenty centers were academic hospitalbased pulmonary clinics, 5 were community-based pulmonary clinics, and 2 were community-based primary care clinics. Eligible patients had to have had at least 1 exacerbation of COPD that required treatment with systemic steroids or antibiotics within the 12 months before randomization. Additional inclusion criteria were age older than 35 years; a history of 10 pack-years or more of cigarette smoking; and documented chronic airflow obstruction, with an FEV1FVC ratio less than 0.70 and a postbronchodilator FEV1 less than 65% of the predicted value. We excluded patients with a history of physician-diagnosed asthma before 40 years of age; those with a history of physician-diagnosed chronic congestive heart failure with known persistent severe left ventricular dysfunction; those receiving oral prednisone; those with a known hypersensitivity or intolerance to tiotropium, salmeterol, or fluticasonesalmeterol; those with a history of severe glaucoma or severe urinary tract obstruction, previous lung transplantation or lung volume reduction surgery, or diffuse bilateral bronchiectasis; and those who were pregnant or were breastfeeding. Persons with a recent COPD exacerbation requiring oral or intravenous antibiotics or steroids were required to wait until treatment with these agents had been discontinued for 28 days before entering the study. Randomization and Interventions We randomly assigned patients to 1 of 3 treatment groups for 52 weeks: tiotropium (Spiriva [Boehringer Ingelheim Pharma, Ingelheim, Germany]), 18 g once daily, plus placebo inhaler, 2 puffs twice daily; tiotropium, 18 g once daily, plus salmeterol (Serevent [GlaxoSmithKline, Research Triangle Park, North Carolina]), 25 g/puff, 2 puffs twice daily; or tiotropium, 18 g once daily, plus fluticasonesalmeterol (Advair [GlaxoSmithKline]), 250/25 g/puff, 2 puffs twice daily. Randomization was done through central allocation of a randomization schedule that was prepared from a computer-generated random listing of the 3 treatment allocations, blocked in variable blocks of 9 or 12 and stratified by site. Neither research staff nor patients were aware of the treatment assignment before or after randomization. All study patients were provided with inhaled albuterol and were instructed to use it when necessary to relieve symptoms. Any treatment with inhaled corticosteroids, long-acting 2-agonists, and anticholinergics that the patient may have been using before entry was discontinued on entry into the study. Therapy with other respiratory medications, such as oxygen, antileukotrienes, and methylxanthines, was continued in all patient groups. Tiotropium was administered by using a Handihaler device (Boehringer Ingelheim). Study drugs were administered through a pressurized metered-dose inhaler using a spacer device (Aerochamber Plus, Trudell Medical, London, Ontario, Canada), and patients were taught the correct inhalation technique to ensure adequate drug delivery. The metered-dose inhalers containing placebo, salmeterol, and fluticasonesalmeterol were identical in taste and appearance, and they were enclosed in identical tamper-proof blinding devices. The medication canisters within the blinding devices were stripped of any identifying labeling. Adherence to therapy was assessed by weighing the returned inhaler canisters. Measurements and Outcomes The primary outcome was the proportion of patients in each treatment group who experienced a COPD exacerbation within 52 weeks of randomization. Respiratory exacerbations were defined, according to the 2000 Aspen Lung Conference Consensus definition, as a sustained worsening of the patients respiratory condition, from the stable state and beyond normal day-to-day variations, necessitating a change in regular medication in a patient with underlying COPD (18). An acute change in regular COPD medications was defined as physician-directed, short-term use of oral or intravenous steroids, oral or intravenous antibiotics, or both therapies. Secondary outcomes were the mean number of COPD exacerbations per patient-year; the total number of exacerbations that resulted in urgent visits to a health care provider or emergency department; the number of hospitalizations for COPD; the total number of hospitalizations for all causes; and changes in health-related quality of life, dyspnea, and lung function. Health-related quality of life was assessed by using the St. Georges Respiratory Questionnaire (19), dyspnea was assessed by using the Transitional Dyspnea Index (20) and the dyspnea domain of the Chronic Respiratory Disease Questionnaire (21), and lung function was assessed by measuring the FEV1 according to established criteria of the American Thoracic Society. Follow-up Procedures Patients were monitored for exacerbations by monthly telephone calls. Exacerbations and all secondary outcomes were also assessed through patient visits at baseline and at 4, 20, 36, and 52 weeks after randomization. For every suspected exacerbation, we contacted both the patient and the patients treating physician to ensure that the medical encounter had been prompted by acute respiratory symptoms and a full report, including physician, emergency department, and hospital records that described the circumstances of each suspected exacerbation, was prepared. The assembled data from the visit for the suspected exacerbation were presented to a blinded adjudication committee for review, and the committee confirmed whether the encounter met the study definition of COPD exacerbation. For the purposes of the trial, we considered that a patient had experienced a new COPD exacerbation if he or she had not been receiving oral steroids and antibiotics for at least 14 days after the previous exacerbation. Patients were followed for the full 52-week duration of the trial, and primary and secondary outcomes were recorded throughout the 1-year period regardless of whether patients had experienced an exacerbation or discontinued treatment with study medications. We did not break the study blinding for patients who prematurely discontinued treatment with study medications. Adverse events were captured by the research coordinators through monthly patient telephone interviews and at scheduled patient visits by using checklists of potential side effects. Physicians rated events as expected or unexpected, and they were asked to rate event severity and attribute causality of adverse events to the study drugs. Statistical Analysis We designed the study to detect an 18% absolute d

Distribution of nitric oxide synthase in normal and cirrhotic human liver

Chronic liver disorders represent a serious health problem, considering that 300 million people worldwide are hepatitis B virus carriers, and 8,000–10,000 patients per year, in the U.S. alone, die as a result of liver failure caused by hepatitis C infection. Nitric oxide synthase (NOS) regulates hepatic vasculature; however, the patterns of expression and activity of NOS proteins in healthy and diseased human livers are unknown. Sections of diseased (n = 42) and control livers (n = 14) were collected during orthotopic liver transplants and partial hepatectomy. The diseased sections included alcoholic cirrhosis, viral hepatitis, cholestasis, acute necrosis, and uncommon pathologies including α1-anti-trypsin disorder. The endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were studied by using the citrulline assay, Western immunoblot, immunohistochemistry, and in situ hybridization. The systemic generation of plasma NO metabolites was measured by HPLC. In control livers, Ca2+-dependent and –independent NOS activities were identified by Western analysis as eNOS and iNOS, respectively. The eNOS was uniformly distributed in the hepatocytes and also detected in the endothelium of hepatic arteries, terminal hepatic venules, sinusoids, and in biliary epithelium. The iNOS was detected in hepatocytes and localized mainly in the periportal zone of the liver acinus. This pattern of distribution of eNOS and iNOS in normal liver was confirmed by in situ hybridization. In diseased livers, there was a significant increase in Ca2+-independent NOS with the corresponding strong appearance of iNOS in the cirrhotic areas. The eNOS was translocated to hepatocyte nuclei. Thus, eNOS and iNOS proteins are differentially expressed in healthy human liver, and this expression is significantly altered in cirrhotic liver disorders.

Managing Dyspnea in Patients with Advanced Chronic Obstructive Pulmonary Disease: A Canadian Thoracic Society Clinical Practice Guideline

Dyspnea is a cardinal symptom of chronic obstructive pulmonary disease (COPD), and its severity and magnitude increases as the disease progresses, leading to significant disability and a negative effect on quality of life. Refractory dyspnea is a common and difficult symptom to treat in patients with advanced COPD. There are many questions concerning optimal management and, specifically, whether various therapies are effective in this setting. The present document was compiled to address these important clinical issues using an evidence-based systematic review process led by a representative interprofessional panel of experts. The evidence supports the benefits of oral opioids, neuromuscular electrical stimulation, chest wall vibration, walking aids and pursed-lip breathing in the management of dyspnea in the individual patient with advanced COPD. Oxygen is recommended for COPD patients with resting hypoxemia, but its use for the targeted management of dyspnea in this setting should be reserved for patients who receive symptomatic benefit. There is insufficient evidence to support the routine use of anxiolytic medications, nebulized opioids, acupuncture, acupressure, distractive auditory stimuli (music), relaxation, handheld fans, counselling programs or psychotherapy. There is also no evidence to support the use of supplemental oxygen to reduce dyspnea in nonhypoxemic patients with advanced COPD. Recognizing the current unfamiliarity with prescribing and dosing of opioid therapy in this setting, a potential approach for their use is illustrated. The role of opioid and other effective therapies in the comprehensive management of refractory dyspnea in patients with advanced COPD is discussed.

Regional Citrate Anticoagulation in Continuous Venovenous Hemodiafiltration

Over the past several years, continuous venovenous hemodiafiltration (CVVHDF) using pump-driven devices has gained wide acceptance as a form of renal replacement therapy for critically ill patients with acute renal failure. More recently, regional citrate anticoagulation has proven useful as a method of anticoagulating CVVHDF circuits, particularly in those patients at high risk for bleeding. However, an easy and convenient method for guiding the dose of citrate infusion has not previously been described. We describe the use of an algorithm using posthemofilter levels of ionized calcium to guide the dose of administered regional citrate on the survival time and urea and creatinine clearances of 24 Hospal AN69HF hemofilters. Nine patients with acute and chronic renal failure requiring CVVHDF were studied. The median filter survival time when using the postfilter ionized calcium algorithm was 3.4 days, with a survival probability of 46% (95% confidence interval [CI], 17 to 71). Random-effects linear regression analysis did not show a significant decline in blood-side urea clearance (P = 0.041) or creatinine clearance (P = 0. 308). Moreover, definite bleeding complications occurred with an incidence rate of 0.045/person-day on citrate anticoagulation (95% CI, 0.006 to 0.16), and occult bleeding occurred with an incidence rate of 0.091/person-day on citrate anticoagulation (95% CI, 0.03 to 0.23). Guiding regional citrate anticoagulation through the use of posthemofilter ionized calcium levels is a safe and effective method of prolonging filter life during CVVHDF.

Reevaluation of Diagnosis in Adults With Physician-Diagnosed Asthma.

Importance Although asthma is a chronic disease, the expected rate of spontaneous remissions of adult asthma and the stability of diagnosis are unknown. Objective To determine whether a diagnosis of current asthma could be ruled out and asthma medications safely stopped in randomly selected adults with physician-diagnosed asthma. Design, Setting, and Participants A prospective, multicenter cohort study was conducted in 10 Canadian cities from January 2012 to February 2016. Random digit dialing was used to recruit adult participants who reported a history of physician-diagnosed asthma established within the past 5 years. Participants using long-term oral steroids and participants unable to be tested using spirometry were excluded. Information from the diagnosing physician was obtained to determine how the diagnosis of asthma was originally made in the community. Of 1026 potential participants who fulfilled eligibility criteria during telephone screening, 701 (68.3%) agreed to enter into the study. All participants were assessed with home peak flow and symptom monitoring, spirometry, and serial bronchial challenge tests, and those participants using daily asthma medications had their medications gradually tapered off over 4 study visits. Participants in whom a diagnosis of current asthma was ultimately ruled out were followed up clinically with repeated bronchial challenge tests over 1 year. Exposure Physician-diagnosed asthma established within the past 5 years. Main Outcomes and Measures The primary outcome was the proportion of participants in whom a diagnosis of current asthma was ruled out, defined as participants who exhibited no evidence of acute worsening of asthma symptoms, reversible airflow obstruction, or bronchial hyperresponsiveness after having all asthma medications tapered off and after a study pulmonologist established an alternative diagnosis. Secondary outcomes included the proportion with asthma ruled out after 12 months and the proportion who underwent an appropriate initial diagnostic workup for asthma in the community. Results Of 701 participants (mean [SD] age, 51 [16] years; 467 women [67%]), 613 completed the study and could be conclusively evaluated for a diagnosis of current asthma. Current asthma was ruled out in 203 of 613 study participants (33.1%; 95% CI, 29.4%-36.8%). Twelve participants (2.0%) were found to have serious cardiorespiratory conditions that had been previously misdiagnosed as asthma in the community. After an additional 12 months of follow-up, 181 participants (29.5%; 95% CI, 25.9%-33.1%) continued to exhibit no clinical or laboratory evidence of asthma. Participants in whom current asthma was ruled out, compared with those in whom it was confirmed, were less likely to have undergone testing for airflow limitation in the community at the time of initial diagnosis (43.8% vs 55.6%, respectively; absolute difference, 11.8%; 95% CI, 2.1%-21.5%). Conclusions and Relevance Among adults with physician-diagnosed asthma, a current diagnosis of asthma could not be established in 33.1% who were not using daily asthma medications or had medications weaned. In patients such as these, reassessing the asthma diagnosis may be warranted.

Multiple organ dysfunction syndrome : a narrative review

PurposeTo review multiple organ dysfunction syndrome with respect to: 1) clinical measurement systems; 2) molecular mechanisms; and 3) therapeutic directions based upon molecular mechanisms.MethodsThe Medline, Cochrane, and Best Evidence databases (1996 to 2000), conference proceedings, bibliographies of review articles were searched for relevant articles. Key index words were multiple organ failure, multiple system organ dysfunction, sepsis, septic shock, shock, systemic inflammatory response syndrome. Outcomes prospectively defined were death and physiological reversal of end organ failure.ResultsMultiple organ dysfunction/failure (MODS) is the most common cause for death in intensive care units. The recognition of this syndrome in the last 30 yr may be due to advances in early resuscitation unmasking these delayed sequelae in those that would have died previously. Multiple organ dysfunction occurs after shock of varied etiologies and may be the result of unbridled systemic inflammation. As yet, therapy directed to prevent or improve MODS has not dramatically altered outcomes.ConclusionMultiple organ dysfunction may serve as useful measure of disease severity for risk adjustment and outcome marker for quality of care and therapy provided. Anesthesiologists treating shock patients will note the subsequent development of MODS in the critical care unit and may be required to provide anesthetic support to these patients.RésuméObjectifPasser en revue la documentation sur le syndrome de défaillance multiviscérale en regard: 1) des systèmes de mesure clinique; 2) des mécanismes moléculaires et 3) des indications thérapeutiques fondées sur ces mécanismes.MéthodeOn a consulté les bases de données de Medline, Cochrane et Best Evidence (1996 à 2000), les actes de conférences, les bibliographies d’articles de revues afin de trouver des articles pertinents. Les mots-clés ont été multiple organ failure, multiple system organ dysfunction, sepsis, septic shock, shock, systemic inflammatory response syndrome. L’évolution, en prospective, est la mort ou le renversement physiologique de la défaillance organique.RésultatsLe syndrome de défaillance/déficience multiviscérale (SDMV) est la cause la plus fréquente de mort des malades à l’unité des soins intensifs. La reconnaissance de ce syndrome au cours des 30 dernières années tient sans doute aux progrès réalisés en réanimation précoce qui ont permis de dévoiler des séquelles à retardement chez ceux qui seraient morts auparavant. La défaillance multiviscérale survient après un choc de causes diverses et peut être le résultat d’une foudroyante inflammation généralisée. À ce jour, le traitement visant à prévenir ou à réduire la manifestation du SDMV n’en a pas beaucoup modifié l’évolution.ConclusionLa défaillance multiviscérale peut servir de mesure utile de la sévérité d’une atteinte au moment de juger des risques et de marqueur de l’évolution en vue des soins de qualité et d’une thérapie à administrer. Les anesthésiologistes qui traitent des malades en choc devront noter l’évolution du SDMV à l’unité des soins intensifs, car ils pourraient être appelés à y fournir un soutien anesthésique.

Targeting membrane-expressed IgE B cell receptor with an antibody to the M1 prime epitope reduces IgE production

A humanized monoclonal antibody that targets the membrane IgE B cell receptor was associated with improvements in asthmatic airway responses. Asthma Antibody Clears the Air A humanized antibody may be the key for treating allergic asthma. Gauvreau et al. report that quilizumab—a humanized monoclonal antibody that targets the membrane immunoglobulin E (IgE) B cell receptor—led to reductions in total and allergen-specific serum IgE that were sustained for 6 months after dosing and were associated with improvements in allergen-induced early and late asthmatic airway responses. A monoclonal antibody that neutralizes IgE can effectively treat asthma in the clinic; however, use is limited by dosing restrictions and it does not prevent new IgE production. Inhibiting IgE production by targeting membrane IgE–expressing cells may enable more subjects to be treated and less frequent dosing, and has the potential for sustained effects upon the cessation of therapy. Elevated serum levels of both total and allergen-specific immunoglobulin E (IgE) correlate with atopic diseases such as allergic rhinitis and allergic asthma. Neutralization of IgE by anti-IgE antibodies can effectively treat allergic asthma. Preclinical studies indicate that targeting membrane IgE–positive cells with antibodies against M1 prime can inhibit the production of new IgE and significantly reduce the levels of serum IgE. We report results from two trials that investigated the safety, pharmacokinetics, and activity of quilizumab, a humanized monoclonal antibody targeting specifically the M1 prime epitope of membrane IgE, in subjects with allergic rhinitis (NCT01160861) or mild allergic asthma (NCT01196039). In both studies, quilizumab treatment was well tolerated and led to reductions in total and allergen-specific serum IgE that lasted for at least 6 months after the cessation of dosing. In subjects with allergic asthma who were subjected to an allergen challenge, quilizumab treatment blocked the generation of new IgE, reduced allergen-induced early and late asthmatic airway responses by 26 and 36%, respectively, and reduced allergen-induced increases in sputum eosinophils by ~50% compared with placebo. These studies indicate that targeting of membrane IgE–expressing cells with anti-M1 prime antibodies can prevent IgE production in humans.

OX40L blockade and allergen‐induced airway responses in subjects with mild asthma

The OX40/OX40L interaction contributes to an optimal T cell response following allergic stimuli and plays an important role in the maintenance and reactivation of memory T effector cells.

Respiratory function after cardiac surgery

STUDY OBJECTIVE Cardiac surgery is complicated by decreased postoperative respiratory muscle strength and spirometry with accompanying increased atelectasis. The specific respiratory symptoms attributable to these physiologic changes are unknown, and this study looked at the symptoms and underlying physiology. DESIGN Convenience sampling of observational cohort. SETTING Tertiary care university hospital. PATIENTS One hundred thirty-eight patients undergoing elective surgery were enrolled. INTERVENTIONS Changes from admission to 8-week postoperative values in atelectasis, pleural effusions, spirometry (forced vital capacity and forced expiratory volume in one second), and respiratory muscle strength (negative inspiratory pressure) were measured. These physiologic changes were compared with changes in respiratory symptoms of cough, wheeze, phlegm, and dyspnea on walking up a slight hill noted from admission to 8-week follow-up by stepward logistic regression. MEASUREMENTS AND RESULTS Spirometry and negative inspiratory pressure decreased and atelectasis increased from admission to discharge. These disturbances had only incompletely resolved at 8-week follow-up. Some patients reported fewer symptoms of cough (11%), phlegm (9%), wheeze (35%), and dyspnea (46%) at 8 weeks follow-up. Other patients reported increased symptoms of cough (15%), phlegm (10%), wheeze (6%), and dyspnea (4%) at 8 weeks follow-up. Residual atelectasis at 8 weeks was predictive of fewer symptoms of dyspnea (odds ratio [OR] 0.335, p = 0.199; 95% confidence interval [CI] 0.188, 0.597), increased symptoms of dyspnea (OR 855, p = 0.006; 95% CI 6.6, 11052), and increased symptoms of cough (OR 260, p = 0.023; 95% CI 2.13, 31829). Negative inspiratory pressure at 8 weeks was predictive of fewer symptoms of dyspnea (OR 1.05, p = 0.032; 95% CI 1.02, 1.09) and increased symptoms of wheeze (OR 0.7, p = 0.45; 95% CI 0.533, 0999). Forced vital capacity at 8 weeks was predictive of increased symptoms of wheeze (OR 0.005; p = 0.015; 95% CI 0.0060, 0.775). CONCLUSIONS Postoperative changes in respiratory muscle strength and spirometry can persist up to at least 8 weeks postoperatively. Many patients report a change in respiratory symptoms of cough, phlegm, dyspnea, or wheeze. The change in respiratory symptoms at 8 weeks is correlated with residual respiratory muscle weakness, decrease in spirometry, and residual atelectasis.

The nonspecific inflammatory response to injury.

PurposeThe role of the nonspecific inflammatory response in causing injury related to surgery has become better understood over the last decade. There are complex interactions between neutrophils, cytokines and nitric oxide metabolites that may cause organ injury following surgery. The purpose of this review is to summarize some of the processes causing injury through these nonspecific pathways.MethodsA review of the medical and anaesthetic literature related to inflammation, neutrophils and pro-inflammatory cytokines were performed using Medline. Bibliographies of relevant articles were searched and additional articles were then selected and reviewed.ResultsPro-inflammatory cytokines, such as tumour necrosis factor, are released in response to a variety of noxious stimuli (e.g. burns, sepsis, or CABG surgery). These cytokines cause activation of neutrophils with increased upregulation of adhesion complexes on neutrophils and vascular endothelium. Nitric oxide synthase activity is also increased with a resultant increased production of nitric oxide. The increased nitric oxide concentration in the presence of Superoxide free radicals secreted by activated neutrophils forms peroxynitrite, a more reactive and toxic molecule. Once this process is initiated, diffuse organ injury can result. Although some information related to specific anaesthetics is available, firm recommendations related to clinical practice cannot be made.ConclusionsThere is a complex interplay of inflammatory mediators that can cause injury. Although specific clinical applications for manipulating these pathways are not yet generally available, this area holds promise to develop new techniques to improve outcomes following surgery.RésuméObjectifLa connaissance du rôle de la réaction inflammatoire non spécifique, causant une atteinte liée à la chirurgie, s’est développée pendant la dernière décennie. Il y a des interactions complexes entre les polynucléaires neutrophiles, les cytokines et les métabolites de l’oxyde nitrique qui peuvent entraîner une lésion organique à la suite d’une chirurgie. Le but de cette revue est de résumer quelques-uns des procédés mis en cause dans les lésions survenant selon ces interactions non spécifiques.MéthodeUne revue de la documentation médicale et anesthésique sur l’inflammation, les polynucléaires neutrophiles et les cytokines pro-inflammatoires a été faite à l’aide de Medline. Nous avons consulté les bibliographies des articles pertinents et nous avons alors choisi et revu des articles supplémentaires.RésultatsLes cytokines pro-inflammatoires, comme le facteur nécrosant des tumeurs, sont libérées en réaction à une variété de stimuli nocifs (brûlures, maladie infectieuse ou pontage aorto-coronaire). Ces cytokines provoquent une activation des polynucléaires neutrophiles accompagnée d’une régulation positive accrue des complexes adhésifs sur les polynucléaires neutrophiles et sur l’endothélium vasculaire. Lactivité de la NO-synthase est aussi augmentée, ce qui résulte en une production accrue d’oxyde nitrique. L’augmentation de la concentration d’oxyde nitrique en présence des radicaux libres superoxydes, sécrétés par les polynucléaires neutrophiles activés, forme le peroxynitrite, une molécule plus réactive et plus toxique. Une fois ce processus enclenché, une lésion organique diffuse peut survenir. Bien que des informations concernant des anesthésiques spécifiques soient accessibles, des recommandations fermes reliées à la pratique ne peuvent être faites.ConclusionIl existe une interaction complexe des médiateurs inflammatoires pouvant causer des lésions. Quoique les applications cliniques spécifiques de la manipulation de ces voies métaboliques ne soient généralement pas encore disponibles, cela constitue un domaine prometteur de développement de nouvelles techniques pour améliorer la situation postopératoire.