Markers of myocardial damage and inflammation in unstable coronary artery disease.
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Angina, Unstable↗
Biomedical subjects
B H Cuthbertson
Publications and source records attributed to B H Cuthbertson.
Consider position of patient to prevent ventilator-associated pneumonia.
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Humans↗
Effect of inhaled nitric oxide on key mediators of the inflammatory response in patients with acute lung injury.
OBJECTIVE: Inhaled nitric oxide is used to treat hypoxia associated with acute lung injury. Endogenous nitric oxide regulates inflammatory responses, but the effect of inhaled nitric oxide therapy is unknown. We hypothesized that inhaled nitric oxide may alter inflammatory responses and endogenous nitric oxide synthase activity. DESIGN: A randomized, prospective interventional study. SETTING: A university hospital's general intensive care unit. PATIENTS: Thirty-two patients with acute lung injury. INTERVENTIONS: Patients who responded to test doses of nitric oxide were randomized to ventilator therapy with and without inhaled nitric oxide. The inhaled concentration of nitric oxide was determined by dose titration at 0, 2, 10, and 40 ppm and the minimum concentration used, which resulted in an increase in the PaO2/FIO2 ratio of at least 25%. MEASUREMENTS AND MAIN RESULTS: Patients were followed up for 30 days or until death, and bronchoalveolar lavage (BAL) was performed at 0, 24, and 72 hrs. Nitric oxide synthase activity was measured spectrophotometrically, and myeloperoxidase, elastase, interleukin-8, and leukotrienes were measured in BAL fluid by enzyme immunoassay. Total nitrite and lipid peroxides in serum were measured colorimetrically. Nitric oxide synthase activity decreased (p = .01) and total nitrite increased (p = .02) in patients receiving inhaled nitric oxide. Other markers of inflammation in BAL fluid did not change. Lipid peroxide concentrations also did not alter. CONCLUSIONS: The decrease in activity of nitric oxide synthase in patients receiving nitric oxide is likely to be the result of feedback inhibition of the enzyme. This study shows that inhaled nitric oxide has no effect on several markers of the inflammatory response system and does not lead to increased oxidant stress.
Acute Disease↗
Inhaled nitric oxide.
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Administration, Inhalation↗
The role of the intensive care unit in the management of the critically ill surgical patient.
Surgical patients make up 60-70% of the work load of intensive care units in the UK. There is a recognised short fall in the resource allocation for high dependency units (HDUs) and intensive care units (ICUs) in this country, despite repeated national audits urging that this resource be increased. British ICUs admit patients later and with higher severity of illness scores than elsewhere and this leads to higher ICU mortality. How can this situation be improved? Scoring systems that allow selection of appropriate patients for admission to ICU and avoid inappropriate admission are still in development. Pre-operative admission and optimisation in ICU is rare in this country despite increasing evidence to support this practice in high risk surgical patients. Early admission to ICU, with potential improvement in outcomes, could also be achieved using multi-disciplinary medical emergency teams. These teams would be alerted by ward staff in response to set specific conditions and physiological criteria. These proposals are still under trial but may offer benefit by reducing mortality in critically ill surgical patients.
Critical Illness↗
The effect of nitric oxide and peroxynitrite on apoptosis in human polymorphonuclear leukocytes.
In acute lung injury, neutrophil apoptosis may be important in regulating the inflammatory process by controlling neutrophil numbers and thus activity. Exogenous inhaled nitric oxide is now a widely used therapy in patients with acute lung injury, and its effects on apoptosis may be important. We investigated the effect of nitric oxide and peroxynitrite on apoptosis in lipopolysaccharide stimulated polymorphonuclear leukocytes as a model of nitric oxide-treated lung injury. Cells were incubated for up to 16 h with and without 1.7 microg/ml lipopolysaccharide and the nitric oxide donor GEA-3162 or the peroxynitrite donor SIN-1. Apoptosis was assessed using flow cytometry following annexin-V staining, after 4, 6, 8, and 16 h. Data were assessed using Kruskal-Wallis analysis of variance or Mann-Whitney U-test as appropriate. Annexin-V staining increased spontaneously over 16 h in untreated cells (p = .0002) and incubation with either 1000 microM SIN-1 or 10 microM GEA-3162 increased annexin staining at early time points in nonactivated cells. Apoptosis was attenuated when cells were exposed to lipopolysaccharide and both nitric oxide and peroxynitrite dose dependently inhibited this suppression at all time points and was most apparent at 16 h (p = .004 and .001, respectively). Exposure of activated neutrophils to exogenous nitric oxide or peroxynitrite has marked influences on apoptosis. This work has implications for the modulation of neutrophil function within the lung in patients with lung injury who receive inhaled nitric oxide therapy.
Annexin A5↗
The effects of nitric oxide and peroxynitrite on interleukin-8 and elastase from lipopolysaccharide-stimulated whole blood.
UNLABELLED: Inhaled nitric oxide is now widely used in the treatment of hypoxemia and pulmonary hypertension in critically ill patients. Interleukin-8 (IL-8) and neutrophil elastase are important markers of the onset and severity of acute lung injury. We studied the effects of nitric oxide and peroxynitrite on IL-8) and elastase accumulation in lipopolysaccharide-activated whole blood. The nitric oxide donor (GEA-3162) did not affect IL-8 accumulation (P = 0.195) but did cause an increase in elastase accumulation (P = 0.007). The peroxynitrite donor (SIN-1) caused an increase in both IL-8 accumulation (P = 0.0004) and elastase accumulation (P = 0.007). The lack of effect of nitric oxide could be explained by the scavenging of nitric oxide by hemoglobin. These results suggest that modulation of the inflammatory response may occur during inhaled nitric oxide therapy in the critically ill. IMPLICATIONS: Inhaled nitric oxide, used in lung injury, reacts within the lung, forming peroxynitrite. We investigated the effect of nitric oxide and peroxynitrite on interleukin-8 and elastase release by white cells during inflammation. Nitric oxide and peroxynitrite had marked effects on elastase and interleukin-8, which suggests modulation of the inflammatory response.
Free Radical Scavengers↗
Nitric oxide delivery systems.
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Drug Delivery Systems↗
UK guidelines for the use of inhaled nitric oxide therapy in adult ICUs. American-European Consensus Conference on ALI/ARDS.
OBJECTIVE: Although unlicensed, inhaled nitric oxide (NO) therapy is now widely used in the United Kingdom. Our aim was to produce guidelines for the clinical application of inhaled NO in adult intensive care practice, based upon the current level of published information. METHODS: The published data regarding the use of inhaled NO in the acute respiratory distress syndrome and right-sided cardiac failure was presented, analysed and discussed. Recommendations based on these data as well as on current experience in the United Kingdom were formulated. DESIGN: An expert group comprising intensive care specialists from within the United Kingdom, representatives from the European Society of Intensive Care Medicine and the Society of Critical Care Medicine and individuals from the Departments of Health and Industry related to the field was assembled. RESULTS: United Kingdom guidelines for the indications, contraindications, dose, delivery, monitoring and scavenging of inhaled NO therapy were produced. CONCLUSIONS: The need for additional quality research to establish evidence of efficacy and safety was emphasized. The guidelines are designed to act within the context of current practice and knowledge and should be revised as further data emerge.
Acute Disease↗
Use of inhaled nitric oxide in British intensive therapy units.
The use of inhaled nitric oxide in the critically ill has increased significantly over the past few years but little published information exists on standards for current practice. Sixty-four intensive therapy units in the UK were surveyed by questionnaire from which 54 (84.4%) satisfactory replies were received. We present the survey results and put forward recommendations based on current literature and our own clinical experience for the safe use of inhaled nitric oxide.
Administration, Inhalation↗
Effect of exogenous nitric oxide and superoxide on interleukin-8 from human polymorphonuclear leucocytes.
Patients with acute inflammatory lung injury are commonly treated with inhaled nitric oxide. Nitric oxide has profound immunoregulatory effects. Increased concentrations of the cytokine interleukin-8 (IL-8) in bronchoalveolar lavage fluid has been associated with disease severity. We have investigated the effects of a nitric oxide donor and a combined nitric oxide-superoxide donor on lipopolysaccharide-mediated accumulation of IL-8 from cultured human neutrophils. Interleukin-8 was measured in culture supernatant after 20 h using enzyme immunoassay. The combined nitric oxide-superoxide donor, 3-morpholinosydnonimine (SIN-1), dose-dependently decreased lipopolysaccharide-mediated IL-8 accumulation (P < 0.01). SIN-1 also decreased IL-8 accumulation from unstimulated neutrophils (P < 0.001). In contrast, the pure nitric oxide donor, 1,2,3,4-oxatriazolium 5-amino chloride (GEA-3162), increased stimulated IL-8 accumulation (P < 0.01) and also increased IL-8 accumulation in unstimulated cells (P < 0.002). Nitric oxide and superoxide have profound effects on IL-8. These results have important implications for the treatment of patients with acute lung injury with inhaled nitric oxide.
Cell Culture Techniques↗
Inhaled nitric oxide.
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Administration, Inhalation↗
Inotropic agents in the critically ill.
Inotropic agents are commonly used in critically ill patients. This heterogeneous group of drugs are potentially hazardous if used without a good understanding of cardiovascular physiology and pathophysiology and without due attention to some general principles for their use. We suggest guidelines for the administration of these agents in all clinical settings.
Cardiotonic Agents↗
Nitric oxide in critical care medicine.
Few areas of medicine have failed to be affected by the discovery of nitric oxide and the unravelling of its many physiological and pathophysiological roles. Possibly no other area of medicine has this discovery had so many potential therapeutic applications as in the field of critical care medicine. But will this widespread interest in nitric oxide result in the promised revolution in clinical care?
Administration, Inhalation↗