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European Neurology 1998Treatment with the combination of almitrine-raubasine increases both arterial oxygen partial pressure and haemoglobin oxygen saturation, reflecting an actual increase in... (Review)
Review
Treatment with the combination of almitrine-raubasine increases both arterial oxygen partial pressure and haemoglobin oxygen saturation, reflecting an actual increase in the oxygen content of arterial blood. Furthermore, at the trans-cerebral carotid artery/internal jugular vein level, the treatment increases cerebral arterio-venous oxygen and glucose differences, suggesting an actual increase both in oxygen and glucose availability and uptake in cerebral tissues. The increased glucose transfer to the brain is supported also by enhancement of the 3H-deoxyglucose uptake induced by drug pre-treatment both in normoxia and hypoxia. Both almitrine and raubasine act at cerebral mitochondrial levels by decreasing the 'loss' of the 'biological' free energy for phosphorylation supported by the age-related drop in the cerebral enzyme activities, such as phosphofructokinase, pyruvate dehydrogenase and citrate synthase. Furthermore, the components interfere with the alterations induced by peroxidative stress acting at the level of cytochrome c, cytochrome c oxidase and succinate dehydrogenase. Treatment with the combination almitrine-raubasine increases the concentration of noradrenaline metabolites, while alteration of the dopaminergic system is less important. The interference with the noradrenergic system is possibly linked to the electroencephalographic changes induced by drug treatment: increasing alpha-rhythm distribution and reactivity, and increases in beta-rhythm amplitude. Pharmacological effects of almitrine-raubasine, obtained in experimental conditions, correlate with clinical therapeutic efficacy, e.g., in the treatment of cognitive disorders associated with ageing and other cerebral and neurosensory impairments. It is difficult to summarise, in a few pages, the large number of papers related to the cerebral pharmacometabolic and pharmacodynamic activities of the almitrine-raubasine combination. Thus, this review presents in sequential steps some of the interrelated research in humans and laboratory animals which describes in a critical way preclinical to clinical results.
Topics: Almitrine; Blood Glucose; Brain; Cerebrovascular Circulation; Drug Combinations; Energy Metabolism; Humans; Neuroprotective Agents; Oxygen; Partial Pressure; Yohimbine
PubMed: 9516073
DOI: 10.1159/000052068 -
Lancet (London, England) Aug 1988
Clinical Trial
Topics: Almitrine; Humans; Peripheral Nervous System Diseases; Piperazines
PubMed: 2899747
DOI: 10.1016/s0140-6736(88)92387-2 -
The European Respiratory Journal Dec 1999
Topics: Administration, Inhalation; Almitrine; Bronchodilator Agents; Drug Therapy, Combination; Humans; Injections, Intravenous; Nitric Oxide; Respiratory Distress Syndrome; Respiratory System Agents; Treatment Outcome
PubMed: 10624749
DOI: 10.1183/09031936.99.14612449 -
Journal of Cardiothoracic and Vascular... Aug 2014Almitrine enhances hypoxic pulmonary vasoconstriction (HPV) and can improve hypoxemia related to one-lung ventilation (OLV). Studies using almitrine have been conducted... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Almitrine enhances hypoxic pulmonary vasoconstriction (HPV) and can improve hypoxemia related to one-lung ventilation (OLV). Studies using almitrine have been conducted without inhaled anesthetics because they could inhibit HPV, counteracting the effect of almitrine. This hypothesis, however, has not been confirmed. This study's aim was to evaluate whether almitrine could improve oxygenation when administered during OLV with sevoflurane anesthesia.
DESIGN
A prospective, randomized, double-blind, placebo-controlled trial.
SETTING
A tertiary care, university teaching hospital.
PARTICIPANTS
Thirty adult patients undergoing open-chest thoracic surgery.
INTERVENTIONS
Patients were assigned randomly to receive almitrine or placebo during OLV. Respiratory and hemodynamic variables were recorded continuously. Anesthesia was maintained with sevoflurane and remifentanil. Intraoperative techniques and medical teams were the same all over the study.
MEASUREMENTS AND MAIN RESULTS
Respiratory and hemodynamic variables were measured during two-lung ventilation and during open-chest OLV. Two-way repeated-measures analysis of variance was used to compare the effects of almitrine and placebo. During OLV, PaO2 and shunt fraction worsened in all patients without significant differences between groups. At 30-minutes of OLV, PaO2 was 184±67 mmHg in the almitrine group and 145±56 mmHg in the placebo group, while shunt fraction were 31%±6% and 36%±13%, respectively. Mean pulmonary artery pressure was higher in the almitrine group (31±5 v 24±5 mmHg, p<0.001).
CONCLUSIONS
During anesthesia with sevoflurane for open-chest OLV, almitrine failed to improve oxygenation and increased pulmonary artery pressure. The combination of sevoflurane and almitrine should, therefore, be avoided.
Topics: Adolescent; Adult; Aged; Almitrine; Anesthesia, General; Anesthetics, Inhalation; Blood Gas Analysis; Double-Blind Method; Female; Hemodynamics; Humans; Hypoxia; Lung; Male; Methyl Ethers; Middle Aged; Monitoring, Intraoperative; One-Lung Ventilation; Oxygen Consumption; Prospective Studies; Respiratory System Agents; Sevoflurane; Thoracic Surgical Procedures; Young Adult
PubMed: 24016684
DOI: 10.1053/j.jvca.2013.03.019 -
Critical Care Medicine Feb 2021
Topics: Almitrine; COVID-19; Humans; Pharmaceutical Preparations; Respiratory Distress Syndrome; Respiratory Insufficiency; SARS-CoV-2
PubMed: 33186137
DOI: 10.1097/CCM.0000000000004765 -
Minerva Anestesiologica Mar 2023Almitrine, a drug enhancing hypoxic pulmonary vasoconstriction, has been proposed as a rescue therapy for refractory hypoxemia in COVID related acute respiratory...
BACKGROUND
Almitrine, a drug enhancing hypoxic pulmonary vasoconstriction, has been proposed as a rescue therapy for refractory hypoxemia in COVID related acute respiratory distress syndrome (C-ARDS). We aimed at investigating the response to almitrine depending on the cause of ARDS (COVID vs. non-COVID).
METHODS
Monocenter retrospective study from 2014 to 2021. All patients diagnosed with moderate to severe ARDS and treated with almitrine as rescue therapy for refractory hypoxemia were studied. Factor independently associated with oxygenation response to almitrine infusion were determined.
RESULTS
Sixty patients with ARDS and treated with almitrine were analyzed, 36 (60%) due to SARS-CoV-2 infection and 24 (40%) due to other causes. Baseline PaO2/FiO2 was 78 [61-101] mmHg, 76% had at least one prone positioning before the start of almitrine infusion. Median PaO2/FiO2 increased by +38 [7-142] mmHg (+61% [10-151]) after almitrine infusion. PaO2/FiO2 increased by +134 [12-186] mmHg in non-COVID ARDS (NC-ARDS) and by +19 [8-87] mmHg in C-ARDS. The increase in PaO2/FiO2 was lower in C-ARDS than in NC-ARDS (P=0.013). In multivariable analysis, C-ARDS, non-invasive ventilation and concomitant use of norepinephrine were independently associated with a decreased oxygenation response to almitrine infusion.
CONCLUSIONS
Our study reports a highly variable response to almitrine infusion in ARDS patients with refractory hypoxemia. Independent factors associated with a reduced oxygenation response to almitrine infusion were: COVID ARDS, concomitant use of norepinephrine, and non-invasive ventilatory strategy.
Topics: Humans; Almitrine; Retrospective Studies; COVID-19; SARS-CoV-2; Hypoxia; Respiratory Distress Syndrome; Norepinephrine
PubMed: 36287391
DOI: 10.23736/S0375-9393.22.16736-2 -
Bulletin Europeen de Physiopathologie... Aug 1987
Review
Topics: Almitrine; Animals; Humans; Lung Diseases, Obstructive; Piperazines; Respiration
PubMed: 3318970
DOI: No ID Found -
Clinical Neuropharmacology 1990During recent years many studies on the electroencephalogram (EEG) changes induced by almitrine-raubasine (Duxil) have been performed in elderly patients and in animals.... (Review)
Review
During recent years many studies on the electroencephalogram (EEG) changes induced by almitrine-raubasine (Duxil) have been performed in elderly patients and in animals. This article gives an overview of three questions raised by their results. Is there a simple addition of the raubasine and almitrine effects when they are coadministered? Are the EEG effects of this treatment dependent on the patient's disease? To what extent could EEG studies provide some knowledge about the mechanism of action of almitrine-raubasine therapy? In adult (8 months) and aged (22 months) rats the EEG changes induced by the coadministration of almitrine and raubasine were significantly different from the addition of individual almitrine and raubasine EEG effects. In adult rats the coadministration induced slighter EEG changes than those predicted by the addition of almitrine and raubasine effects. In aged rats, the coadministration induced a decrease in delta-theta power not predictable from the effects of almitrine or raubasine. These results could be taken as an indication that some biological targets are common for the two drugs and that the coadministration results in pharmacological effects more complicated than a simple addition of raubasine and almitrine properties. After 3 weeks of treatment in aged healthy subjects, the coadministration induced an increase in the alpha and beta power with a slight decrease of delta and beta-1 powers. In patients with cognitive decline of probable degenerative origin, 3 months of therapy with almitrine-raubasine was mainly associated with a decreased delta and theta power and a slight increase in high frequency components of the alpha band.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Aged; Aging; Almitrine; Animals; Drug Combinations; Electroencephalography; Humans; Rats; Secologanin Tryptamine Alkaloids; Yohimbine
PubMed: 2093418
DOI: 10.1097/00002826-199013003-00006 -
European Journal of Respiratory... 1986
Review
Topics: Almitrine; Animals; Hemodynamics; Humans; Piperazines; Respiration; Structure-Activity Relationship
PubMed: 3536559
DOI: No ID Found -
EClinicalMedicine Oct 2022Severe hypoxemia in patients with COVID-19 pneumonia might result from hypoxic pulmonary vasoconstriction, contributing to ventilation/perfusion (V/Q) mismatch. Because...
Effect of intravenous almitrine on intubation or mortality in patients with COVID-19 acute hypoxemic respiratory failure: A multicentre, randomised, double-blind, placebo-controlled trial.
BACKGROUND
Severe hypoxemia in patients with COVID-19 pneumonia might result from hypoxic pulmonary vasoconstriction, contributing to ventilation/perfusion (V/Q) mismatch. Because almitrine improves V/Q, it might reduce the risk for mechanical ventilation (MV) in such patients. Our primary objective was to determine the effect of almitrine on the need for MV at day 7.
METHODS
In a randomised double-blind placebo-controlled trial involving 15 ICUs, patients hospitalized for COVID-19 pneumonia and experiencing acute hypoxemic respiratory failure were randomly assigned to receive 5 days of intravenous low-dose (2 µg.kg.min) almitrine or placebo. The primary outcome was endotracheal intubation for MV or death within 7 days after randomisation. Secondary outcomes included in-hospital mortality, 28-day mortality, number of ventilator-free days, number of days in the ICU and the hospital, and treatment discontinuation for pre-specified adverse effects. This trial was registered with ClinicalTrials.gov, NCT04357457.
FINDINGS
Between September 3, 2020 and September 25, 2021 181 patients were enrolled and randomly assigned to almitrine (n=89) or placebo (n=92). 179 patients (excluding two who withdrew from the study) were included in the intention-to-treat analysis (mean age: 60·1 years; 34% women) and analyzed. On day 7, the primary endpoint occurred in 32 patients assigned to almitrine (36%) and in 37 patients assigned to placebo (41%), for a difference of -4·3% (95% confidence interval: -18·7% to 10·2%). Secondary outcomes (28-day mortality, in-hospital mortality, ventilator-free days at day 28, days in the ICU and the hospital, and treatment discontinuation for pre-specified adverse effects) did not differ between the two groups.
INTERPRETATION
In patients with COVID-19 acute hypoxemic respiratory failure, low-dose almitrine failed in reducing the need for MV or death at day 7.
FUNDING
Programme Hospitalier de Recherche Clinique (PHRC COVID 2020) funded by the French Ministry of Health, Les Laboratoires Servier (Suresnes, France) providing the study drug free of charge.
PubMed: 36157895
DOI: 10.1016/j.eclinm.2022.101663