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3.
Anesth Analg ; 129(2): e48-e51, 2019 08.
Article En | MEDLINE | ID: mdl-29337729

This single-center case series investigated the effect of almitrine infusion on PaO2/fraction of inspired oxygen (FIO2) in 25 patients on veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. A positive trial was defined as an increase of PaO2/FIO2 ratio ≥20%. Thirty-two trials were performed. Twenty (62.5%, 95% confidence interval, 37.5%-75%) trials in 18 patients were positive, with a median PaO2/FIO2 ratio increase of 35% (25%-43%). A focal acute respiratory distress syndrome and inhaled nitric oxide therapy were more frequent in patients with a positive response to almitrine. We observed no complications of almitrine use.


Almitrine/administration & dosage , Extracorporeal Membrane Oxygenation , Respiration/drug effects , Respiratory Distress Syndrome/therapy , Respiratory System Agents/administration & dosage , Adult , Almitrine/adverse effects , Extracorporeal Membrane Oxygenation/adverse effects , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Recovery of Function , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/physiopathology , Respiratory System Agents/adverse effects , Retrospective Studies , Time Factors , Treatment Outcome
4.
J Cardiothorac Vasc Anesth ; 28(4): 919-24, 2014 Aug.
Article En | MEDLINE | ID: mdl-24016684

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.


Almitrine/administration & dosage , Anesthesia, General/methods , Hemodynamics/drug effects , Hypoxia/drug therapy , Methyl Ethers/administration & dosage , One-Lung Ventilation/methods , Oxygen Consumption/drug effects , Adolescent , Adult , Aged , Anesthetics, Inhalation/administration & dosage , Blood Gas Analysis , Double-Blind Method , Female , Humans , Hypoxia/metabolism , Hypoxia/physiopathology , Lung/metabolism , Lung/physiopathology , Male , Middle Aged , Monitoring, Intraoperative , Prospective Studies , Respiratory System Agents/administration & dosage , Sevoflurane , Thoracic Surgical Procedures , Young Adult
5.
Minerva Anestesiol ; 80(5): 517-25, 2014 May.
Article En | MEDLINE | ID: mdl-24299918

BACKGROUND: Lung ultrasound can be used at bedside to assess initial lung morphology in hypoxemic patients. We hypothesized that blood flow in consolidated lung and therefore effects of inhaled nitric oxide (iNO) and intravenous almitrine could be directly assessed using Doppler transesophageal echocardiography (TEE). METHODS: We conducted a prospective study including 13 ALI patients with consolidated left lower lobe (LLL). Regional arterial and venous flow signals within the consolidation were recorded with TEE using Doppler at baseline, after iNO (5 ppm), almitrine (4 µg/kg/min) and their combination. Pulmonary shunt (Qs/Qt) was measured using a Swan-Ganz catheter. Arterial and venous velocity time integral (VTI), peak velocity (Vmax) and mean velocity (Vmean) were measured. Patients were responders if PaO2 basal value increased by 20% after iNO or almitrine. RESULTS: In 7 NO responders, iNO decreased regional arterial VTI (8.1±1.9 vs. 6.7±1.6, P<0.05). In 8 almitrine responders, almitrine decreased regional arterial and venous VTI (from 6.7±2.0 to 4.5±2.3 cm and from 12.3±5.4 to 7.5±3.8 cm, respectively, P<0.05). For all patients, combination of iNO and almitrine decreased regional arterial and venous VTI (from 7.3±0.3 to 4.1±0.3 cm and from 12.6±0.7 to 6.7±0.8 cm, respectively, P<0.05). Arterial and venous Vmean and Vmax significantly decreased. Variations of arterial VTI and venous Vmean were correlated to variations of Qs/Qt (r=.71, P<.001 and r=.62, P<.01, respectively). CONCLUSION: Doppler of consolidated LLL allows assessment of regional pulmonary circulation in ICU settings. It detects changes in flow profiles resulting from the administration of NO and/or almitrine. Further applicability remains to be determined.


Acute Lung Injury/drug therapy , Acute Lung Injury/physiopathology , Almitrine/therapeutic use , Bronchodilator Agents/therapeutic use , Nitric Oxide/therapeutic use , Pulmonary Circulation/drug effects , Respiratory System Agents/therapeutic use , Acute Lung Injury/diagnostic imaging , Administration, Inhalation , Aged , Almitrine/administration & dosage , Bronchodilator Agents/administration & dosage , Echocardiography, Transesophageal , Female , Humans , Injections, Intravenous , Male , Middle Aged , Nitric Oxide/administration & dosage , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/physiopathology , Respiratory System Agents/administration & dosage
6.
Ter Arkh ; 80(3): 28-33, 2008.
Article Ru | MEDLINE | ID: mdl-18441680

AIM: To elucidate efficacy of a combination almitrine+thiotropium bromide (TB)+pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) of stage II-III complicated with chronic respiratory failure (CRF). MATERIAL AND METHODS: Efficacy of therapy was compared in two groups of patients: group 1 (n = 22) received TB in a dose 18 mcg/day for one year, almitrine in a dose 10 mg/kg/day for 3 months, an 8 week course of PR, group 2 (n = 17) received TB and PR. The treatment efficacy was determined by spirometric parameters of external respiration function, blood gases, dyspnea indices, exercise tolerance assessed by 6-min walk test, quality of life (St. George Hospital Respiratory Questionnaire). RESULTS: Group 1 patients walked longer distance after a course of PR and 1 year later (by 90.5 +/- 25.4 and 44.5 +/- 10.2 m, respectively, p < 0.05), had reduced desaturation measured by pulsoxym-etry at the end of 6-min walk test, increased PaO2 in baseline under 70 mmHg (by 5.8 +/- 1.2 mmHg, p > 0.05), decreased exacerbation rate per 1 patient a year (by 25%). CONCLUSION: Combination treatment with TB, almitrine and PR is indicated for COPD patients with moderate hypoxemia.


Almitrine/administration & dosage , Bronchodilator Agents/administration & dosage , Exercise Therapy/methods , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/rehabilitation , Scopolamine Derivatives/administration & dosage , Administration, Inhalation , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Male , Middle Aged , Quality of Life , Tiotropium Bromide , Treatment Outcome
7.
Br J Anaesth ; 95(3): 410-6, 2005 Sep.
Article En | MEDLINE | ID: mdl-16024585

BACKGROUND: Almitrine combined with inhaled nitric oxide (NO) can prevent hypoxia during one-lung ventilation (OLV). The optimal dose of almitrine that would provide therapeutic advantage with few side-effects during open-chest OLV has not been established. METHODS: Forty-two patients undergoing thoracotomy were randomly allocated to three groups: placebo, almitrine 4 microg kg(-1) min(-1) and inhaled NO 10 p.p.m. (ALM4+NO), and almitrine 16 microg kg(-1) min(-1) and inhaled NO 10 p.p.m. (ALM16+NO). Gas exchange, haemodynamic and respiratory variables and plasma concentrations of almitrine and lactate were monitored. Measurements were obtained with the patient awake (baseline), after induction of anaesthesia with two-lung ventilation (control 2LV), 20 min after treatment (2LV+T), and then at 10, 20 and 30 min of OLV (OLV10', OLV20' and OLV30') with FI(O2)1. RESULTS: In the placebo group, OLV impaired Pa(O2) and increased pulmonary shunt [16 (SD 7) kPa and 42 (10)% respectively]. These improved with ALM4+NO [26 (10) kPa and 31 (7)%; P<0.001]. ALM16+NO further improved PaO2) to 36 (13) kPa (P<0.0001) but gave no improvement in the shunt. Mean pulmonary artery pressure was similar in the placebo and ALM4+NO groups [20 (4) vs 23 (5) mm Hg], whereas it was increased in the ALM16+NO group to 28 (8) mm Hg (P<0.01). Plasma concentrations of almitrine and lactate were unaltered by the treatments. CONCLUSIONS: Low-dose almitrine (4 microg kg(-1) min(-1)) together with inhaled NO significantly improves oxygenation during open-chest OLV, without modifying pulmonary haemodynamics. An increased dose of almitrine (16 microg kg(-1) min(-1)) with inhaled NO further improves arterial oxygenation, but also increases mean pulmonary artery pressure.


Almitrine/administration & dosage , Hypoxia/prevention & control , Intraoperative Complications/prevention & control , Nitric Oxide/therapeutic use , Thoracotomy , Adolescent , Adult , Aged , Almitrine/therapeutic use , Anthropometry , Dose-Response Relationship, Drug , Double-Blind Method , Drug Therapy, Combination , Female , Hemodynamics/drug effects , Humans , Hypoxia/etiology , Male , Middle Aged , Oxygen/blood , Partial Pressure , Prospective Studies , Respiration, Artificial/methods
8.
Respir Med ; 97(6): 599-605, 2003 Jun.
Article En | MEDLINE | ID: mdl-12814142

BACKGROUND: Almitrine bismesylate (AB) is a peripheral chemoreceptor agonist which is believed to improve oxygenation of COPD patients with chronic hypoxaemia, probably by improving the ventilation perfusion mismatch. We studied the long-term effects of AB in COPD patients with chronic hypoxaemia. DESIGN: Prospective, randomised, double-blind, placebo-controlled trial. SETTING: Eight hundred bed teaching hospital with a catchment population of 350,000 inhabitants. PATIENT RECRUITMENT: COPD outpatients consulting between September 95 and September 99. INCLUSION CRITERIA: (1) COPD (FEV1 < 50%). (2) PaO2 < or = 65 mmHg. (3) Stable arterial blood gases (ABG), spirometry (S) and clinical state. EXCLUSION CRITERIA: Asthma, restrictive disease, sleep apnoea syndrome, advanced renal or hepatic disease, peripheral neuropathy, use of respiratory stimulants or psychotrophic drugs. TREATMENT: AB 1 mg/kg/day (weight < 75 kg = 50 mg/day; weight > or = 75 kg = 100 mg/day) in an intermittent schedule with resting periods of 1 month after the third, 6th and 9th months during 1 year. INSTRUMENTATION: Stabilisation period: S, ABG. Run-in period: S, ABG, 6-min walking test (WT), nocturnal pulse oximetry (NP) and quality of life evaluation (CRQ). Third, 6th and 9th months: S, ABG. End of the study: S, ABG, WT, NP, CRQ. STATISTICS: ANOVA for repeated measurements. RESULTS: Two hundred and eighty-nine patients were evaluated and 81 were included in the study. Sixty-six were followed for 6 months, 53 for 9 months and 42 for 1 year. Almitrine and placebo groups did not present significant differences in ABG and S in the 6th, 9th and 12th months. Evolution in WT, NP and CRQ were similar in the two groups. No relevant side-effects were detected: only two patients stopped treatment (one placebo and one AB). CONCLUSION: In an intermittent schedule, although well tolerated, at doses of 1 mg/kg/day, AB was not effective in long-term treatment of chronic hypoxemia in COPD patients.


Almitrine/administration & dosage , Hypoxia/drug therapy , Pulmonary Disease, Chronic Obstructive/drug therapy , Respiratory System Agents/administration & dosage , Aged , Analysis of Variance , Carbon Dioxide/blood , Chronic Disease , Dose-Response Relationship, Drug , Double-Blind Method , Female , Forced Expiratory Volume/physiology , Humans , Male , Oxygen/blood , Partial Pressure , Prospective Studies , Quality of Life , Vital Capacity/physiology
9.
Anesth Analg ; 94(4): 830-4, table of contents, 2002 Apr.
Article En | MEDLINE | ID: mdl-11916780

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.


Almitrine/administration & dosage , Hemodynamics/drug effects , Oxygen/blood , Pneumonectomy , Respiration, Artificial , Respiratory System Agents/administration & dosage , Blood Pressure/drug effects , Carbon Dioxide/blood , Double-Blind Method , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Prospective Studies , Pulmonary Circulation/drug effects , Respiration, Artificial/methods
10.
Intensive Care Med ; 27(3): 574-9, 2001 Mar.
Article En | MEDLINE | ID: mdl-11355128

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.


Almitrine/administration & dosage , Disease Models, Animal , Fluorocarbons/administration & dosage , Hemodynamics/drug effects , Liquid Ventilation/methods , Pulmonary Gas Exchange/drug effects , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/therapy , Respiratory System Agents/administration & dosage , Almitrine/pharmacology , Animals , Blood Gas Analysis , Combined Modality Therapy , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Drug Synergism , Drug Therapy, Combination , Fluorocarbons/pharmacology , Hydrocarbons, Brominated , Prospective Studies , Pulmonary Wedge Pressure/drug effects , Random Allocation , Respiration, Artificial , Respiratory Distress Syndrome/metabolism , Respiratory System Agents/pharmacology
11.
Crit Care Med ; 29(1): 32-6, 2001 Jan.
Article En | MEDLINE | ID: mdl-11176154

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.


Almitrine/pharmacology , Hypoxia/drug therapy , Respiratory Distress Syndrome/drug therapy , Respiratory System Agents/pharmacology , Ventricular Function, Right/drug effects , Adult , Aged , Almitrine/administration & dosage , Female , Hemodynamics/drug effects , Humans , Hypoxia/etiology , Infusions, Intravenous , Linear Models , Male , Middle Aged , Prospective Studies , Pulmonary Gas Exchange/drug effects , Respiratory Distress Syndrome/complications , Respiratory System Agents/administration & dosage , Statistics, Nonparametric
12.
Intensive Care Med ; 27(11): 1737-43, 2001 Nov.
Article En | MEDLINE | ID: mdl-11810116

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.


Almitrine/administration & dosage , Pulmonary Gas Exchange/drug effects , Respiratory Distress Syndrome/drug therapy , Respiratory System Agents/administration & dosage , Administration, Inhalation , Adrenergic alpha-Agonists/administration & dosage , Analysis of Variance , Bronchodilator Agents/administration & dosage , Female , Hemodynamics/drug effects , Humans , Infusions, Intravenous , Male , Middle Aged , Nitric Oxide/administration & dosage , Norepinephrine/administration & dosage , Oxygen/metabolism , Prospective Studies , Respiratory Distress Syndrome/complications , Shock, Septic/complications , Shock, Septic/drug therapy , Treatment Outcome
13.
Intensive Care Med ; 26(4): 434-41, 2000 Apr.
Article En | MEDLINE | ID: mdl-10872136

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.


Almitrine/pharmacology , Hemodynamics/drug effects , Pulmonary Gas Exchange/drug effects , Respiratory Insufficiency/drug therapy , Respiratory System Agents/pharmacology , Almitrine/administration & dosage , Analysis of Variance , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Prospective Studies , Respiratory Insufficiency/physiopathology , Respiratory System Agents/administration & dosage , Swine
14.
Intensive Care Med ; 26(2): 221-8, 2000 Feb.
Article En | MEDLINE | ID: mdl-10784314

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.


Almitrine/pharmacology , Bronchodilator Agents/pharmacology , Nitric Oxide/pharmacology , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/physiopathology , Respiratory System Agents/pharmacology , Ventilation-Perfusion Ratio/drug effects , Administration, Inhalation , Almitrine/administration & dosage , Analysis of Variance , Animals , Bronchodilator Agents/administration & dosage , Female , Hemodynamics , Humans , Infant, Newborn , Lung Injury , Nitric Oxide/administration & dosage , Prospective Studies , Pulmonary Gas Exchange , Respiratory System Agents/administration & dosage , Swine
16.
Am J Respir Crit Care Med ; 160(2): 473-9, 1999 Aug.
Article En | MEDLINE | ID: mdl-10430716

It has been suggested that the increase in PO(2) observed with nitric oxide (NO) should be enhanced by the addition of a vasoconstrictor agent. The vasoconstrictor used in combination with NO should mimic or enhance hypoxic vasoconstriction. The aim of this study was to evaluate the respiratory and hemodynamic effects of norepinephrine (a nonspecific vasoconstrictor), almitrine bismesylate (a specific pulmonary vasoconstrictor), and inhaled NO, alone or together. During a 6-mo period, 16 patients presenting with ARDS were prospectively investigated. On inclusion, no patient was receiving cardiovasoactive drugs. The protocol consisted of seven consecutive phases: baseline, norepinephrine (in order to obtain a 3 mm Hg rise in mean pulmonary arterial pressure [Ppa]), almitrine bismesylate (16 micrograms/kg/min), inhaled NO (20 ppm delivered during inspiration), norepinephrine + inhaled NO, almitrine bismesylate + inhaled NO, almitrine bismesylate + norepinephrine + inhaled NO. General factorial analysis of variance showed that inhaled NO and almitrine bismesylate increased oxygenation (p < 0.0001). Norepinephrine had no effect on oxygenation. A synergistic effect between inhaled NO and almitrine bismesylate was found (p < 0.05), whereas norepinephrine did not affect the response to inhaled NO. Nitric oxide produced a significant decrease in Ppa and pulmonary vascular resistances (PVRI) (p < 0.0001). Both almitrine bismesylate and norepinephrine induced an increase in Ppa (p < 0.0001). Norepinephrine increased PVRI (p < 0.002), whereas almitrine bismesylate had no effect on PVRI. The present results support the hypothesis that a selective pulmonary vasoconstrictor enhances the increase in oxygenation induced by inhaled NO, whereas norepinephrine attenuates this effect.


Almitrine/administration & dosage , Nitric Oxide/administration & dosage , Norepinephrine/administration & dosage , Respiratory Distress Syndrome/drug therapy , Vasoconstrictor Agents/administration & dosage , Administration, Inhalation , Adult , Aged , Aged, 80 and over , Almitrine/adverse effects , Critical Care , Drug Synergism , Drug Therapy, Combination , Female , Hemodynamics/drug effects , Humans , Male , Middle Aged , Nitric Oxide/adverse effects , Norepinephrine/adverse effects , Oxygen/blood , Pulmonary Wedge Pressure/drug effects , Respiratory Function Tests , Vasoconstrictor Agents/adverse effects
18.
Eur Respir J ; 14(6): 1283-9, 1999 Dec.
Article En | MEDLINE | ID: mdl-10624756

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.


Almitrine/administration & dosage , Nitric Oxide/administration & dosage , Norepinephrine/administration & dosage , Respiratory Distress Syndrome/drug therapy , Respiratory System Agents/administration & dosage , Vasoconstrictor Agents/administration & dosage , Administration, Inhalation , Adult , Aged , Drug Interactions , Drug Therapy, Combination , Female , Hemodynamics/drug effects , Hemodynamics/physiology , Humans , Infusions, Intravenous , Male , Middle Aged , Prospective Studies , Pulmonary Gas Exchange/drug effects , Reference Values , Reproducibility of Results , Respiratory Distress Syndrome/diagnosis , Respiratory Function Tests , Statistics, Nonparametric
19.
Am J Respir Crit Care Med ; 158(6): 1770-7, 1998 Dec.
Article En | MEDLINE | ID: mdl-9847266

Inhaled nitric oxide (iNO), a selective pulmonary vasodilator and intravenously administered almitrine, a selective pulmonary vasoconstrictor, have been shown to increase PaO2 in patients with acute respiratory distress syndrome (ARDS). This prospective study was undertaken to assess the cardiopulmonary effects of combining both drugs. In 48 consecutive patients with early ARDS, cardiorespiratory parameters were measured at control, after iNO 5 ppm, after almitrine 4 micrograms. kg-1. min-1, and after the combination of both drugs. In 30 patients, dose response to 2, 4, and 16 micrograms. kg-1. min-1 of almitrine with and without NO was determined. Almitrine and lactate plasma concentrations were measured in 17 patients. Using pure O2, PaO2 increased by 75 +/- 8 mm Hg after iNO, by 101 +/- 12 mm Hg after almitrine 4 micrograms. kg-1. min-1, and by 175 +/- 18 mm Hg after almitrine combined with iNO (p < 0.001). In 63% of the patients, PaO2 increased by more than 100% with the combination of both drugs. Mean pulmonary artery pressure (Ppa) increased by 1.4 +/- 0.2 mm Hg with almitrine 4 micrograms/kg/ min (p < 0.001) and decreased by 3.4 +/- 0.4 mm Hg with iNO and by 1.5 +/- 0.3 mm Hg with the combination (p < 0.001). The maximum increase in PaO2 was obtained at almitrine concentrations <= 4 micrograms. kg-1. min-1, whereas almitrine increased Ppa dose-dependently. Almitrine plasma concentrations also increased dose-dependently and returned to values close to zero after 12 h. In many patients with early ARDS, the combination of iNO 5 ppm and almitrine 4 micrograms. kg-1. min-1 dramatically increases PaO2 without apparent deleterious effect allowing a rapid reduction in inspired fraction of O2. The long-term consequences of this immediate beneficial effect remain to be determined.


Almitrine/therapeutic use , Nitric Oxide/therapeutic use , Respiratory Distress Syndrome/drug therapy , Respiratory System Agents/therapeutic use , Vasodilator Agents/therapeutic use , Administration, Inhalation , Almitrine/administration & dosage , Almitrine/blood , Analysis of Variance , Blood Pressure/drug effects , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Follow-Up Studies , Heart/drug effects , Humans , Injections, Intravenous , Lactates/blood , Lung/drug effects , Male , Middle Aged , Nitric Oxide/administration & dosage , Oxygen/blood , Positive-Pressure Respiration , Prospective Studies , Pulmonary Artery/drug effects , Respiratory System Agents/administration & dosage , Respiratory System Agents/blood , Shock, Septic/physiopathology , Vascular Resistance/drug effects , Vasoconstrictor Agents/administration & dosage , Vasoconstrictor Agents/blood , Vasoconstrictor Agents/therapeutic use , Vasodilator Agents/administration & dosage
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