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Lancet (London, England) Apr 2002
Topics: Almitrine; Humans; Hypoxia; Intraoperative Complications; Male; Middle Aged; Respiratory System Agents
PubMed: 11965308
DOI: 10.1016/S0140-6736(02)08296-X -
Anesthesia and Analgesia Apr 2002One-lung ventilation (OLV) induces an increase in pulmonary shunt sometimes associated with a decrease in PaO2 despite ventilation with 100% oxygen. PaO2 improvement has... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
UNLABELLED
One-lung ventilation (OLV) induces an increase in pulmonary shunt sometimes associated with a decrease in PaO2 despite ventilation with 100% oxygen. PaO2 improvement has been reported in one-lung ventilated animals receiving IV almitrine, a pulmonary vasoconstrictor. We evaluated the ability of almitrine to prevent a decrease in PaO2 during OLV. Patients without pulmonary hypertension undergoing OLV for lung surgery were randomly assigned to receive either placebo (Group P, n = 8) or almitrine infusion at a rate of 8 microg x kg(-1) x min(-1) (Group A, n = 8) from the start of OLV. Gasometric and hemodynamic values were recorded with the patient in the lateral decubitus position during two-lung ventilation and at 10-min intervals during OLV over a 30-min period (OLV-10, OLV-20, OLV-30). Compared with the values found during two-lung ventilation (434 +/- 22 mm Hg in Group P and 426 +/- 23 mm Hg in Group A), PaO2 decreased at OLV-10 (305 +/- 46 mm Hg), OLV-20 (203 +/- 20 mm Hg), and OLV-30 (178 +/- 18 mm Hg) in Group P (P < 0.05) and at OLV-20 (354 +/- 25 mm Hg) and OLV-30 (325 +/- 17 mm Hg) in Group A (P < 0.05). PaO2 values differed between the groups at OLV-20 and OLV-30 (P < 0.05). Pulmonary artery pressure and cardiac output did not change. In conclusion, 8 microg x kg(-1) x min(-1) IV almitrine prevents and limits the OLV-induced decrease in PaO2 without causing any hemodynamic modification.
IMPLICATIONS
Eight microg x kg(-1) x min(-1) IV almitrine limits one-lung ventilation-induced decrease in PaO2 without causing any hemodynamic modification in patients without pulmonary hypertension.
Topics: Almitrine; Blood Pressure; Carbon Dioxide; Double-Blind Method; Female; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Oxygen; Pneumonectomy; Prospective Studies; Pulmonary Circulation; Respiration, Artificial; Respiratory System Agents
PubMed: 11916780
DOI: 10.1097/00000539-200204000-00010 -
Respiration; International Review of... 2002Diaphragm muscle force and fatigue are key factors in the development of respiratory failure. Almitrine is used to improve ventilatory drive and ventilation-perfusion... (Comparative Study)
Comparative Study
BACKGROUND
Diaphragm muscle force and fatigue are key factors in the development of respiratory failure. Almitrine is used to improve ventilatory drive and ventilation-perfusion matching in respiratory failure. Recently, it has also been shown to improve diaphragm muscle force and endurance in young rats, but it is not known if this effect persists with ageing.
OBJECTIVES
To determine the effects of almitrine on diaphragm contractile properties in young and old rats.
METHODS
In young and old rats, isometric contractile properties were measured in strips of isolated diaphragm muscle in physiological saline solution at 30 degrees C with or without almitrine.
RESULTS
In young animals, almitrine increased twitch tension, reduced half-relaxation time and increased endurance, but had no effect on tetanic tension, contraction time or tension-frequency relationship. Ageing had no effect on endurance, but did reduce twitch and tetanic tension and contraction and half-relaxation time. Almitrine had no effect on contractile tension and kinetics, tension-frequency relationship or on endurance in the old animals.
CONCLUSIONS
Ageing negates the beneficial effects of almitrine on diaphragm muscle force and endurance.
Topics: Aging; Almitrine; Analysis of Variance; Animals; Animals, Newborn; Culture Techniques; Diaphragm; Female; Male; Models, Animal; Muscle Contraction; Muscle Fatigue; Probability; Rats; Rats, Wistar; Reference Values; Sensitivity and Specificity
PubMed: 11844967
DOI: 10.1159/000049374 -
Intensive Care Medicine Nov 2001To evaluate the effects on oxygenation and pulmonary haemodynamics of almitrine bismesylate (AB) 5 microg/kg per minute and 16 microg/kg per minute in ARDS patients...
OBJECTIVE
To evaluate the effects on oxygenation and pulmonary haemodynamics of almitrine bismesylate (AB) 5 microg/kg per minute and 16 microg/kg per minute in ARDS patients responding to and receiving inhaled NO (iNO) and presenting septic shock requiring norepinephrine, while no difference was observed in a previous trial including iNO responders and nonresponders.
DESIGN
Prospective, cohort study.
SETTING
Adult medico-surgical intensive care unit of a university hospital.
PATIENTS
Fifteen patients with ARDS receiving and responding to iNO (10 ppm) and presenting septic shock requiring norepinephrine (mean 0.5+/-0.45 microg/kg per minute, range 0.08- 2.08).
INTERVENTIONS
The protocol consisted of two consecutive phases in a fixed order: continuous intravenous infusion of AB 5 microg/kg per minute for 30 min, and continuous intravenous infusion of AB 16 microg/kg per minute for 30 min.
MEASUREMENTS AND MAIN RESULTS
AB 5 microg/kg per minute significantly increased PaO2/FiO2 ( P<0.05) compared with iNO alone [160 (range 77-450) mmHg vs 122 (range 70-225) mmHg]. AB 16 microg/kg per minute produced a greater increase of PaO2/FiO2 ( P<0.05) when compared with 5 microg/kg per minute [227 (range 84-501) mmHg]. AB did not improve shunt at any dose regimen. AB produced an increase in mean pulmonary arterial pressure (MPAP) from 22+/-5 to 25+/-4 mmHg ( P<0.03). MPAP did not significantly increase between the two doses. Pulmonary vascular resistances and other haemodynamic and respiratory parameters were not affected by almitrine bismesylate.
CONCLUSIONS
These results suggest that it is possible to obtain a further improvement in oxygenation by increasing AB infusion rate in ARDS patients iNO responders receiving norepinephrine. Due to the potential deleterious effects of AB, this strategy should be used in the most severely hypoxaemic patients.
Topics: Administration, Inhalation; Adrenergic alpha-Agonists; Almitrine; Analysis of Variance; Bronchodilator Agents; Female; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Nitric Oxide; Norepinephrine; Oxygen; Prospective Studies; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Respiratory System Agents; Shock, Septic; Treatment Outcome
PubMed: 11810116
DOI: 10.1007/s00134-001-1128-y -
Revue Des Maladies Respiratoires Sep 2001
Clinical Trial Comparative Study Randomized Controlled Trial
Topics: Aged; Almitrine; Female; Humans; Hypoxia; Male; Middle Aged; Oxygen; Placebos; Pulmonary Disease, Chronic Obstructive; Respiratory System Agents; Treatment Outcome
PubMed: 11787328
DOI: No ID Found -
Canadian Journal of Physiology and... Nov 2001Spike frequency was recorded in the nerve of the isolated superfused first gill arch of the bullfrog larva, Rana catesbeiana and the response to different superfusate...
Spike frequency was recorded in the nerve of the isolated superfused first gill arch of the bullfrog larva, Rana catesbeiana and the response to different superfusate PO2 was evaluated. In the metamorphic tadpole, spike frequency increased significantly when the superfusate PO2 was decreased (mean +/- SEM): 8.5 +/- 1.6 Hz at 650 Torr, 11.7 +/- 1.9 Hz at 140 Torr, 13.3 +/- 1.8 Hz at 65 Torr, 14.8 +/- 2.4 Hz at 0 Torr (ANOVA, p = 0.0002). The O2 sensitive chemoreceptor stimulants NaCN and almitrine also increased the spike frequency. This study demonstrates the presence of O2 sensitive chemoreceptors in the first gill arch of the tadpole.
Topics: Animals; Chemoreceptor Cells; Gills; In Vitro Techniques; Larva; Neurons, Afferent; Oxygen; Partial Pressure; Rana catesbeiana; Synaptic Transmission
PubMed: 11760099
DOI: No ID Found -
Intensive Care Medicine Aug 2001To compare, in clinical practice, the oxygenation variations related to prone positioning (PP) during mechanical ventilation in ARDS and non-ARDS hypoxemic patients. (Comparative Study)
Comparative Study
OBJECTIVES
To compare, in clinical practice, the oxygenation variations related to prone positioning (PP) during mechanical ventilation in ARDS and non-ARDS hypoxemic patients.
DESIGN AND SETTING
Prospective observational study of data on consecutive patients treated with the same protocol in the intensive care unit (ICU) of a university hospital.
PATIENTS
From May 1996 to December 1998, 226 PP periods without adjunction of nitric oxide (NO) inhalation and/or almitrine bismesylate infusion, performed in 59 mechanically ventilated hypoxemic patients (arterial oxygen tension/fractional inspired oxygen (PaO2/FIO2) ratio <300 mmHg) with no evidence of left ventricular failure, were included in this study.
MEASUREMENTS
Arterial blood gas was measured before the PP, at 1 h from the beginning of the PP, at the end of the PP and 1 h after returning to the supine position.
RESULTS
We analyzed 136 PP periods in 34 non-ARDS patients (60.2%) and 90 in 25 ARDS patients. The PP was repeated and the duration of the PP periods was: 10.6+/-0.22 h. The PP during the mechanical ventilation appeared to be safe and well tolerated. A PaO2/FIO2 ratio improvement at the end of the PP period, occurred for 196 periods (86.7%) with a mean PaO2/FIO2 ratio increase of +46.4+/-0.03% at the end of the PP periods compared to the baseline supine value. The PaO2/FIO2 ratio variations at 1 h after the start of the PP, at the end of the PP period and at 1 h after the return to supine were not different in ARDS or non-ARDS hypoxemic patients. The PaO2/FIO2 ratio improvement appeared to be more intense and more rapid in ARDS patients.
CONCLUSIONS
In about 90% of periods, PP improved the PaO2/FIO2 ratio in patients with ARDS as well as in hypoxemic patients with non-ARDS. Studies are necessary to determine the impact of PP on survival and the mechanical ventilation duration in ARDS or non-ARDS hypoxemic patients.
Topics: Analysis of Variance; Humans; Hypoxia; Oxygen; Positive-Pressure Respiration; Prone Position; Prospective Studies; Respiratory Distress Syndrome; Statistics, Nonparametric; Supine Position
PubMed: 11511948
DOI: 10.1007/s001340101023 -
Respiratory Medicine Jul 2001Almitrine (A) and medroxyprogesterone acetate (MA) given separately improve arterial blood gases in some patients with chronic obstructive pulmonary disease (COPD); the... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Almitrine (A) and medroxyprogesterone acetate (MA) given separately improve arterial blood gases in some patients with chronic obstructive pulmonary disease (COPD); the aim of this study was to assess the effect of the two drugs given together. Forty-eight patients with irreversible COPD and hypoxaemia were prospectively enrolled into a 14-day run-in period and received single-blind oral treatment with double placebo. Patients whose PaO2 remained stable (less than 10% change; n = 29, 25 males, mean age 65.6 years) were included in a 14-day active treatment period and randomly assigned to three groups. They received double-blind oral treatment with: A (50 mg bid, group A, n = 10); MA (20 mg tid, group MA, n = 9); A (50 mg bid) and MA (20 mg tid, group A+MA, n = 10). Anthropometric and spirometric measurements were similar in the three groups and so were the arterial blood gas values at the beginning and the end of the run-in period. At the end of the active treatment period, blood gas changes (mean+/-SE) were significantly different between groups (P<0.05, Kruskal-Wallis test), with improvement in both hypoxaemia and hypercapnia in group A+MA only: delta PaO2 = 7.4+/-1.9 mmHg, delta PaCO2 = -5.1+/-1.7 m mHg (P<0.05, Wilcoxon test). In short-term treatment, the association of A and MA is more efficient than either drug alone at improving arterial blood gases in COPD patients.
Topics: Aged; Almitrine; Blood Gas Analysis; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Female; Humans; Lung Diseases, Obstructive; Male; Medroxyprogesterone Acetate; Middle Aged; Prospective Studies; Respiratory System Agents; Statistics, Nonparametric; Treatment Outcome
PubMed: 11453318
DOI: 10.1053/rmed.2001.1110 -
Anesthesiology Mar 2001Inhaled prostacyclin and intravenous almitrine have both been shown to improve pulmonary gas exchange in acute lung injury (ALI). This study was performed to investigate...
BACKGROUND
Inhaled prostacyclin and intravenous almitrine have both been shown to improve pulmonary gas exchange in acute lung injury (ALI). This study was performed to investigate a possible additive effect of prostacyclin and almitrine on pulmonary ventilation-perfusion (VA/Q) ratio in ALI compared with inhaled prostacyclin or intravenous almitrine alone.
METHODS
Experimental ALI was established in 24 pigs by repeated lung lavage. Animals were randomly assigned to receive either 25 ng.kg(-1).min(-1) inhaled prostacyclin alone, 1 microg.kg(-1).min(-1) almitrine alone, 25 ng.kg(-1).min(-1) inhaled prostacyclin in combination with 1 microg.kg(-1).min(-1) almitrine, or no specific treatment (controls) for 30 min. For each intervention, pulmonary gas exchange and hemodynamics were analyzed and VA/Q distributions were calculated using the multiple inert gas elimination technique. The data was analyzed within and between the groups by analysis of variance for repeated measurements, followed by the Student-Newman-Keuls test for multiple comparison when analysis of variance revealed significant differences.
RESULTS
All values are expressed as mean +/- SD. In controls, pulmonary gas exchange, hemodynamics, and VA/Q distribution remained unchanged. With prostacyclin alone and almitrine alone, arterial oxygen partial pressure (PaO2) increased, whereas intrapulmonary shunt (QS/QT) decreased (P < 0.05). Combined prostacyclin and almitrine also increased PaO2 and decreased QS/QT (P < 0.05). When compared with either prostacyclin or almitrine alone, the combined application of both drugs revealed no additional effect in gas exchange or VA/Q distribution.
CONCLUSIONS
The authors conclude that, in this experimental model of ALI, the combination of 25 ng.kg(-1).min(-1) prostacyclin and 1 microg.kg(-1).min(-1) almitrine does not result in an additive improvement of pulmonary gas exchange or VA/Q distribution when compared with prostacyclin or almitrine alone.
Topics: Almitrine; Analysis of Variance; Animals; Antihypertensive Agents; Drug Interactions; Epoprostenol; Female; Hemodynamics; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Respiratory System Agents; Swine; Ventilation-Perfusion Ratio
PubMed: 11374607
DOI: 10.1097/00000542-200103000-00017 -
Intensive Care Medicine Mar 2001To determine possible additive effects of combined high-dose partial liquid ventilation (PLV) and almitrine bismesylate (ALM) on pulmonary gas exchange and hemodynamics...
OBJECTIVES
To determine possible additive effects of combined high-dose partial liquid ventilation (PLV) and almitrine bismesylate (ALM) on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury (ALI).
DESIGN AND SETTING
Prospective, controlled animal study in an animal research facility of a university hospital.
INTERVENTIONS
ALI was induced in 12 anesthetized and mechanically ventilated pigs by repeated wash-out of surfactant. After initiation of PLV with 30 ml/kg perfluorocarbon the animals were randomly assigned to receive either accumulating doses of ALM (0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 micrograms/kg per minute) for 30 min each (n = 6) or the solvent malic acid (n = 6).
MEASUREMENT AND RESULTS
Pulmonary gas exchange and hemodynamics were measured at the end of each infusion period. Compared to ALI, PLV alone significantly increased arterial oxygen partial pressure (PaO2) and decreased venous admixture (QVA/QT) and mean pulmonary artery pressure (MPAP). Administration of ALM did not result in a further improvement in PaO2, QVA/QT or MPAP compared to PLV alone but decreased PaO2 and increased QVA/QT and MPAP when 16 micrograms/kg per min ALM was compared to PLV alone.
CONCLUSIONS
In an animal model of surfactant depletion induced ALI the combined treatment of PLV and ALM induced no significant improvement in pulmonary gas exchange or hemodynamics when compared to PLV alone. Moreover, high-dose ALM significantly impaired gas exchange and pulmonary hemodynamics.
Topics: Almitrine; Animals; Blood Gas Analysis; Combined Modality Therapy; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Fluorocarbons; Hemodynamics; Hydrocarbons, Brominated; Liquid Ventilation; Prospective Studies; Pulmonary Gas Exchange; Pulmonary Wedge Pressure; Random Allocation; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory System Agents
PubMed: 11355128
DOI: 10.1007/s001340000847