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Critical Care Medicine Jan 2001To evaluate the effects of high-dose almitrine infusion on gas exchange and right ventricular function in patients with severe hypoxemia related to acute respiratory... (Clinical Trial)
Clinical Trial
OBJECTIVE
To evaluate the effects of high-dose almitrine infusion on gas exchange and right ventricular function in patients with severe hypoxemia related to acute respiratory distress syndrome (ARDS).
DESIGN
Prospective study.
SETTING
Medicosurgical intensive care department (ten beds).
PATIENTS
Nine patients with ARDS and severe hypoxemia (PaO2/FIO2 ratio, <150 torr [20 kPa]).
INTERVENTION
High-dose almitrine infusion (16 microg/kg/min for 30 mins).
MEASUREMENTS AND MAIN RESULTS
Gas exchange and hemodynamic parameters were recorded before and after almitrine infusion. Right ventricular function was evaluated by using a fast response thermistor pulmonary artery catheter that allowed measurement of right ventricular ejection fraction and calculation of right ventricular end-diastolic and end-systolic volumes. Almitrine did not significantly alter arterial oxygenation and intrapulmonary shunt. Almitrine increased mean pulmonary arterial pressure (MPAP) from 31 +/- 4 to 33 +/- 4 mm Hg (p < .05), pulmonary vascular resistance index from 353 +/- 63 to 397 +/- 100 dyne x sec/ cm5 x m2 (p < .05), and right ventricular end-systolic volume index from 71 +/- 22 to 77 +/- 21 mL/m2 (p < .05); almitrine decreased right ventricular ejection fraction from 36% +/- 7% to 34% +/- 8% (p < .05). Stroke volume index and cardiac index did not change. The almitrine-induced changes in right ventricular ejection fraction were closely correlated with the baseline MPAP (r2 = .71, p < .01).
CONCLUSION
In patients with severe hypoxemia related to ARDS, high-dose almitrine infusion did not improve arterial oxygenation and impaired the loading conditions of the right ventricle. The decrease in right ventricular ejection fraction induced by almitrine was correlated with the baseline MPAP. Thus, high-dose almitrine infusion may be harmful in ARDS patients with severe hypoxemia and pulmonary hypertension.
Topics: Adult; Aged; Almitrine; Female; Hemodynamics; Humans; Hypoxia; Infusions, Intravenous; Linear Models; Male; Middle Aged; Prospective Studies; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Respiratory System Agents; Statistics, Nonparametric; Ventricular Function, Right
PubMed: 11176154
DOI: 10.1097/00003246-200101000-00007 -
European Journal of Pharmacology Jan 2001The effects of almitrine on the contractile properties of isolated geniohyoid and sternohyoid muscles were determined in physiological salt solution at 30 degrees C in...
The effects of almitrine on the contractile properties of isolated geniohyoid and sternohyoid muscles were determined in physiological salt solution at 30 degrees C in young and old rats. In young rats, almitrine had no effect on twitch or tetanic tension, twitch:tetanic tension ratio, contractile kinetics, active or passive tension-length relationships or frequency-tension relationship in both muscles. Almitrine significantly increased resistance to fatigue in both muscles. In old rats, almitrine had no effect on twitch or tetanic tension, twitch:tetanic tension ratio, contractile kinetics, active or passive tension-length relationships, frequency-tension relationship or fatigue in both muscles. These results show that almitrine, in both young and old rats, has no effect on most of the contractile properties of isolated geniohyoid and sternohyoid muscles. However, almitrine increases resistance to fatigue in both muscles in young but not in old rats.
Topics: Age Factors; Almitrine; Animals; Muscle Contraction; Rats; Rats, Wistar; Respiratory Muscles; Respiratory System Agents
PubMed: 11165230
DOI: 10.1016/s0014-2999(01)00721-x -
Critical Care Medicine Sep 2000To systematically review clinical trials in acute respiratory distress syndrome (ARDS). (Comparative Study)
Comparative Study Review
OBJECTIVE
To systematically review clinical trials in acute respiratory distress syndrome (ARDS).
DATA SOURCES
Computerized bibliographic search of published research and citation review of relevant articles.
STUDY SELECTION
All clinical trials of therapies for ARDS were reviewed. Therapies that have been compared in prospective, randomized trials were the focus of this analysis.
DATA EXTRACTION
Data on population, interventions, and outcomes were obtained by review. Studies were graded for quality of scientific evidence.
MAIN RESULTS
Lung protective ventilator strategy is supported by improved outcome in a single large, prospective trial and a second smaller trial. Other therapies for ARDS, including noninvasive positive pressure ventilation, inverse ratio ventilation, fluid restriction, inhaled nitric oxide, almitrine, prostacyclin, liquid ventilation, surfactant, and immune-modulating therapies, cannot be recommended at this time. Results of small trials using corticosteroids in late ARDS support the need for confirmatory large clinical trials.
CONCLUSIONS
Lung protective ventilator strategy is the first therapy found to improve outcome in ARDS. Trials of prone ventilation and fluid restriction in ARDS and corticosteroids in late ARDS support the need for large, prospective, randomized trials.
Topics: Clinical Trials as Topic; Humans; Prospective Studies; Respiration, Artificial; Respiratory Distress Syndrome; Treatment Outcome
PubMed: 11008997
DOI: 10.1097/00003246-200009000-00034 -
Intensive Care Medicine Apr 2000To determine the dose-response relationship of almitrine (Alm) on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury (ALI). (Clinical Trial)
Clinical Trial Randomized Controlled Trial
OBJECTIVE
To determine the dose-response relationship of almitrine (Alm) on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury (ALI).
DESIGN
Prospective, randomized, controlled study.
METHODS
Twenty anesthetized, tracheotomized and mechanically ventilated (FIO2 1.0) pigs underwent induction of ALI by repeated saline washout of surfactant. Animals were randomly assigned to either receive cumulating doses of Alm intravenously (0.5, 1.0, 2.0, 4.0, 8.0 and 16.0 micrograms.kg-1.min-1) for 30 min each (treatment; n = 10) or to receive the solvent malic acid (controls; n = 10).
MEASUREMENTS AND RESULTS
Measurements of pulmonary gas exchange and hemodynamics were performed at the end of each infusion period. Alm < 4.0 micrograms.kg-1.min-1 improved arterial oxygen pressure (PaO2) (105 +/- 9 mmHg for Alm 1.0 vs 59 +/- 5 mmHg) and decreased intrapulmonary shunt (Qs/Qt) (32 +/- 4% for Alm 1.0 vs 46 +/- 4%) (P < 0.05). Alm > or = 8.0 micrograms.kg-1.min-1 did not improve pulmonary gas exchange compared to controls. When compared to low doses of Alm < 4.0 micrograms.kg-1.min-1, high doses > or = 8.0 micrograms.kg1.min-1 decreased PaO2 (58 +/- 11 mmHg for Alm 16.0) and increased Qs/Qt (67 +/- 10% for Alm 16.0) (P < 0.05).
CONCLUSIONS
In experimental ALI, effects of almitrine on oxygenation are dose-dependent. Almitrine is most effective when used at low doses known to mimic hypoxic pulmonary vasoconstriction.
Topics: Almitrine; Analysis of Variance; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Hemodynamics; Prospective Studies; Pulmonary Gas Exchange; Respiratory Insufficiency; Respiratory System Agents; Swine
PubMed: 10872136
DOI: 10.1007/s001340051178 -
Advances in Experimental Medicine and... 2000
Topics: Almitrine; Anesthesia; Animals; Aortic Bodies; Biguanides; Blood Pressure; Chemoreceptor Cells; Electrophysiology; Heart Rate; Male; Phrenic Nerve; Rats; Rats, Sprague-Dawley; Reflex; Respiration
PubMed: 10849721
DOI: 10.1007/0-306-46825-5_79 -
Intensive Care Medicine Feb 2000To investigate a possible additive effect of combined nitric oxide (NO) and almitrine bismesylate (ALM) on pulmonary ventilation-perfusion (V(A)/Q) ratio.
OBJECTIVE
To investigate a possible additive effect of combined nitric oxide (NO) and almitrine bismesylate (ALM) on pulmonary ventilation-perfusion (V(A)/Q) ratio.
DESIGN
Prospective, controlled animal study.
SETTING
Animal research facility of a university hospital.
INTERVENTIONS
Three conditions were studied in ten female pigs with experimental acute lung injury (ALI) induced by repeated lung lavage: 1) 10 ppm NO, 2) 10 ppm NO with 1 microg/kg per min ALM, 3) 1 microg/ kg per min ALM. For each condition, gas exchange, hemodynamics and V(A)/Q distributions were analyzed using the multiple inert gas elimination technique (MIGET).
MEASUREMENT AND RESULTS
With NO + ALM, arterial oxygen partial pressure (PaO2) increased from 63 +/- 18 mmHg to 202 +/- 97 mmHg while intrapulmonary shunt decreased from 50 +/- 15 % to 26 +/- 12% and blood flow to regions with a normal V(A)/Q ratio increased from 49 +/- 16 % to 72 +/- 15 %. These changes were significant when compared to untreated ALI (p < 0.05) and NO or ALM alone (p < 0.05), although improvements due to NO or ALM also reached statistical significance compared to ALI values (p < 0.05).
CONCLUSIONS
We conclude that NO + ALM results in an additive improvement of pulmonary gas exchange in an experimental model of ALI by diverting additional blood flow from non-ventilated lung regions towards those with normal V(A)/Q relationships.
Topics: Administration, Inhalation; Almitrine; Analysis of Variance; Animals; Bronchodilator Agents; Female; Hemodynamics; Humans; Infant, Newborn; Lung Injury; Nitric Oxide; Prospective Studies; Pulmonary Gas Exchange; Respiratory Insufficiency; Respiratory System Agents; Swine; Ventilation-Perfusion Ratio
PubMed: 10784314
DOI: 10.1007/s001340050051 -
Clinical and Experimental Pharmacology... 20001. Breathing movements stop soon after the induction of hypoxia in foetal animals, a response attributed to the active inhibition of the respiratory centres. Separate... (Review)
Review
1. Breathing movements stop soon after the induction of hypoxia in foetal animals, a response attributed to the active inhibition of the respiratory centres. Separate studies using punctate lesions have identified lateral pontine and thalamic sites in foetal sheep from which respiratory inhibition may arise, but whether either of these loci are actually oxygen sensitive or whether they receive input from other regions responsive to hypoxia, has not been established. 2. FOS immunocytochemistry was used to identify neuronal pools activated by hypoxia in the brain of late-gestation foetal and newborn sheep. FOS-positive cells were found in the pons in regions corresponding to the medial parabrachial and Kolliker-Fuse nuclei and were shown to be catecholaminergic. Neurons in this pontine region were also activated by the piperizine drug almitrine, which, like hypoxia, inhibits respiratory output in the foetus but is a respiratory stimulant in the newborn and adult. Because these pontine neurons do not express FOS protein after challenge with hypoxia or almitrine in the newborn lamb, we argue that they are crucial to the hypoxic inhibition of respiratory activity in foetal life. 3. The role of the placenta in determining these foetal responses and how this may change at birth is discussed.
Topics: Animals; Brain Stem; Chemoreceptor Cells; Female; Fetal Hypoxia; Fetus; Placenta; Pregnancy; Proto-Oncogene Proteins c-fos; Respiration; Sheep
PubMed: 10696538
DOI: 10.1046/j.1440-1681.2000.03201.x -
Chest Feb 2000Sleep has well-recognized effects on breathing, including changes in central respiratory control, airways resistance, and muscular contractility, which do not have an... (Review)
Review
Sleep has well-recognized effects on breathing, including changes in central respiratory control, airways resistance, and muscular contractility, which do not have an adverse effect in healthy individuals but may cause problems in patients with COPD. Sleep-related hypoxemia and hypercapnia are well recognized in COPD and are most pronounced in rapid eye movement sleep. However, sleep studies are usually only indicated in patients with COPD when there is a possibility of sleep apnea or when cor pulmonale and/or polycythemia are not explained by the awake PaO(2) level. Management options for patients with sleep-related respiratory failure include general measures such as optimizing therapy of the underlying condition; physiotherapy and prompt treatment of infective exacerbations; supplemental oxygen; pharmacologic treatments such as bronchodilators, particularly ipratropium bromide, theophylline, and almitrine; and noninvasive positive pressure ventilation.
Topics: Adrenergic beta-Agonists; Almitrine; Carbon Dioxide; Cholinergic Antagonists; Humans; Lung Diseases, Obstructive; Oxygen; Positive-Pressure Respiration; Sleep Apnea, Obstructive; Sleep, REM; Theophylline; Ventilation-Perfusion Ratio
PubMed: 10673475
DOI: 10.1378/chest.117.2_suppl.48s -
Revue Des Maladies Respiratoires Dec 1999The study of respiratory sleep disorders in intensive care is a developing field. Indeed sleep pathology concerns not only pneumologists and neurophysiologists but also... (Comparative Study)
Comparative Study Review
The study of respiratory sleep disorders in intensive care is a developing field. Indeed sleep pathology concerns not only pneumologists and neurophysiologists but also numerous specialties including medicosurgical resuscitation. The advent of "portable" appliances should facilitate access to polysomnography (PSG) for diagnosis of sleep respiratory disorders (RDS) in the intensive care unit. This examination can be appropriate in two separate circumstances. RDS in life-threatening situations (generally respiratory and/or cardiac failure) or when RDS is worsened by the specific conditions of intensive care units: "intensive care-induced RDS". In both cases, easy diagnosis of RDS by PSG allows adjustment of the treatment (corrections of iatrogenic factors, continuous positive airway pressure [CPAP], noninvasive ventilation [NIV], oxygen [O2]. A specific treatment of the well documented RDS is most desirable, as the patients are considered to be at high risk for endotracheal intubation. If diagnosis of RDS is not made during the acute phase, the intensive care physician should be informed of the clinical and paraclinical elements leading to prescription of a delayed polysomnography in order to reduce the risk of further vital distress.
Topics: Acute Disease; Aged; Almitrine; Anti-Inflammatory Agents; Bronchodilator Agents; Critical Care; Diuretics; Female; Heart Failure; Humans; Male; Middle Aged; Oximetry; Oxygen Inhalation Therapy; Polysomnography; Progesterone; Respiration; Respiration, Artificial; Respiratory Insufficiency; Respiratory System Agents; Sleep; Sleep Apnea Syndromes; Theophylline
PubMed: 10637907
DOI: No ID Found -
The European Respiratory Journal Dec 1999The combination of inhaled nitric oxide with almitrine bismesylate has been proposed for the management of acute respiratory distress syndrome in order to divert... (Clinical Trial)
Clinical Trial Comparative Study
The combination of inhaled nitric oxide with almitrine bismesylate has been proposed for the management of acute respiratory distress syndrome in order to divert pulmonary blood flow away from poorly ventilated toward well-ventilated areas. The aims of this prospective and comparative study were to: 1) confirm the beneficial effects on oxygenation of this association; 2) evaluate the haemodynamic effects of this association; and 3) evaluate the influence of noradrenaline (a nonspecific vasoconstrictor) on the modification of gas exchange related to inhaled NO and/or almitrine bismesylate. Forty-one sedated paralysed and ventilated patients were investigated. Haemodynamic and blood gas measurements were performed in a fixed order: baseline; inhalation of NO for 30 min.; intravenous infusion of almitrine bismesylate; and concomitant administration of inhaled NO and almitrine bismesylate. Inhaled NO and almitrine bismesylate increased arterial oxygen tension (Pa,O2)/inspiratory oxygen fraction (FI,O2) (p<0.001). The association of inhaled NO with almitrine bismesylate resulted in a dramatic improvement in Pa,O2/FI,O2 (p<0.0001 versus almitrine bismesylate, p<0.05 versus inhaled NO). In patients receiving noradrenalin (n = 19), almitrine bismesylate had no effect on oxygenation. The present study confirmed that the combination of inhaled NO with almitrine bismesylate improved oxygenation, and demonstrated that almitrine bismesylate has no effect on oxygenation in patients receiving noradrenalin.
Topics: Administration, Inhalation; Adult; Aged; Almitrine; Drug Interactions; Drug Therapy, Combination; Female; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Nitric Oxide; Norepinephrine; Prospective Studies; Pulmonary Gas Exchange; Reference Values; Reproducibility of Results; Respiratory Distress Syndrome; Respiratory Function Tests; Respiratory System Agents; Statistics, Nonparametric; Vasoconstrictor Agents
PubMed: 10624756
DOI: 10.1183/09031936.99.14612839