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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 -
Drugs Sep 1999This article reviews the pharmacological treatment of severely hypoxaemic critically ill patients, notably those with acute respiratory distress syndrome (ARDS), acute... (Review)
Review
This article reviews the pharmacological treatment of severely hypoxaemic critically ill patients, notably those with acute respiratory distress syndrome (ARDS), acute lung injury or the sepsis syndrome. Haemodynamic support in hypotensive patients often initially requires aggressive fluid resuscitation with crystalloids or colloids, combined with vasopressors to maintain adequate end-organ perfusion. The catecholamine of choice in severe hypotension with low systemic resistance is norepinephrine (noradrenaline); dopamine is often used in mild hypotension. Once haemodynamic stabilisation is achieved, loop diuretics such as furosemide (frusemide) are used to obtain the lowest volaemia that guarantees adequate perfusion. If the fraction of inspired oxygen necessary to achieve the satisfactory haemoglobin oxygen saturation of 90% approaches 1, a trial of nitric oxide with or without almitrine is justified. Oxygen consumption can be lowered by treating fever with paracetamol (acetaminophen) and physical cooling. Occasionally, deep sedation using a combination of an opioid (most often morphine or fentanyl) and a benzodiazepine (lorazepam or midazolam) is necessary; in the presence of renal or hepatic insufficiency, propofol is a valid, although expensive, alternative. Paralysis with pancuronium or vecuronium has been associated with critical illness polyneuropathy and is used only as a last resort. Corticosteroids may be indicated in the subacute (fibroproliferative) phase of ARDS. Other anti-inflammatory treatments (such as cytokine antagonists, cyclo-oxygenase inhibitors, antioxidants or monoclonal anti-endotoxin antibodies), as well as surfactant supplementation, have failed to improve prognosis in randomised trials.
Topics: Adjuvants, Pharmaceutic; Anti-Inflammatory Agents; Bronchodilator Agents; Clinical Trials as Topic; Humans; Hypoxia; Oxygen; Respiratory Insufficiency; Surface-Active Agents
PubMed: 10493271
DOI: 10.2165/00003495-199958030-00004 -
Anesthesia and Analgesia Aug 1999
Topics: Administration, Inhalation; Adult; Almitrine; Bronchoalveolar Lavage; Bronchodilator Agents; Hemodynamics; Humans; Infusions, Intravenous; Male; Nitric Oxide; Oxygen; Pulmonary Alveolar Proteinosis; Pulmonary Gas Exchange; Respiration, Artificial; Respiratory System Agents
PubMed: 10439735
DOI: 10.1097/00000539-199908000-00008 -
American Journal of Respiratory and... Aug 1999It 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... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
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.
Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Almitrine; Critical Care; Drug Synergism; Drug Therapy, Combination; Female; Hemodynamics; Humans; Male; Middle Aged; Nitric Oxide; Norepinephrine; Oxygen; Pulmonary Wedge Pressure; Respiratory Distress Syndrome; Respiratory Function Tests; Vasoconstrictor Agents
PubMed: 10430716
DOI: 10.1164/ajrccm.160.2.9809110 -
Minerva Anestesiologica May 1999The improvements in video endoscopic surgical equipment and a growing enthusiasm for minimally invasive surgical approaches, brought video assisted thoracoscopy (VAT) to... (Review)
Review
The improvements in video endoscopic surgical equipment and a growing enthusiasm for minimally invasive surgical approaches, brought video assisted thoracoscopy (VAT) to the practice of surgery for diagnostic and therapeutic procedures. Most of these procedure required a well collapse lung and should be included in the absolute indication for one lung ventilation (OLV) category. The univent tube, is a novel means of achieving bronchial blockade. The bronchial blocker technique has been modified so that the bronchial blocker is passed along a single-lumen endobronchial tube. It was introduced to clinical practice to avoid the need to change the double lumen tube at the conclusion of the procedure. Finally, one of the most interesting future concept to keep adequate oxygenation during OLV, is the ability to modulate the lung circulation. In fact inhaled nitric oxide (NO) and intravenous Almitrine have been combined with additive effects on gas exchange. In case of OLV using that combination will maximize the HPV of the non-dependent lung while dilate the dependent lung to practically eliminate the transpulmonary shunt.
Topics: Anesthesia; Humans; Lung; Respiration, Artificial
PubMed: 10389404
DOI: No ID Found -
Pediatric Research Apr 1999Almitrine is a piperazine derivative known to stimulate breathing in the adult but cause apnea in fetal sheep. In fetal sheep (127-133 d gestation; term = 147 d) we...
Almitrine is a piperazine derivative known to stimulate breathing in the adult but cause apnea in fetal sheep. In fetal sheep (127-133 d gestation; term = 147 d) we confirmed this finding, but found that almitrine (4 mg/kg, i.v. or intra-arterial) had a biphasic effect, briefly stimulating and then suppressing breathing movements for at least 3 h. In 2- to 3-d-old (n = 4) and 7- to 14-d-old (n = 4) lambs almitrine increased both tidal volume and breath frequency, increased arterial partial pressure of oxygen and pH, and decreased partial pressure of carbon dioxide. The changes of tidal volume, partial pressure of oxygen and partial pressure of carbon dioxide were less in the 2- to 3-d-old compared with the 7- to 14-d-old lambs. The distribution of the nuclear phosphoprotein FOS, a marker of neuronal activation was examined in fetal and newborn brains. FOS protein was increased in cardiorespiratory areas of the medulla and pons, in the periaqueductal region of the midbrain, and in the supraoptic and paraventricular regions of the hypothalamus. In the pons, FOS protein was increased in the medial parabrachial and subcoeruleus nuclei in the fetuses but not in the 2- to 3- or 7- to 14-d-old lambs. These observations are similar to those reported for hypoxia, and consistent with the hypothesis that both almitrine and hypoxia inhibit fetal breathing movements by an action on a select group of pontine neurons. Whether these neurons respond directly to these stimuli or receive input from the other centers is yet to be elucidated. The mechanisms that change the almitrine (and hypoxia) response from inhibition to excitation at birth have not been identified, but may be important in preventing apnea in the newborn.
Topics: Almitrine; Animals; Animals, Newborn; Blood Pressure; Brain; Carbon Dioxide; Female; Fetus; Gene Expression Regulation; Heart Rate; Heart Rate, Fetal; Hypothalamus; Medulla Oblongata; Mesencephalon; Neurons; Organ Specificity; Oxygen; Partial Pressure; Pons; Pregnancy; Proto-Oncogene Proteins c-fos; Respiration; Respiratory System Agents; Sheep; Tidal Volume; Trachea
PubMed: 10203146
DOI: 10.1203/00006450-199904010-00013 -
Critical Care Clinics Oct 1998This article reviews pharmacologic approaches to treating acute respiratory distress syndrome (ARDS). The authors discuss the therapeutic effects of ketoconazole,... (Review)
Review
This article reviews pharmacologic approaches to treating acute respiratory distress syndrome (ARDS). The authors discuss the therapeutic effects of ketoconazole, antioxidants, corticosteroids, surfactant, ketanserin, pentoxifylline, bronchodilators, and almitrine in ARDS. Current animal data and proposed mechanics which may foster future pharmacologic therapies are also examined.
Topics: Anti-Inflammatory Agents; Antioxidants; Chemotherapy, Adjuvant; Humans; Immunotherapy; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory System Agents; Steroids
PubMed: 9891629
DOI: 10.1016/s0749-0704(05)70022-1 -
Pneumologie (Stuttgart, Germany) Oct 1998
Clinical Trial
Topics: Almitrine; Humans; Lung Diseases, Obstructive; Respiratory System Agents; Treatment Failure
PubMed: 9847631
DOI: No ID Found -
American Journal of Respiratory and... Dec 1998Inhaled nitric oxide (iNO), a selective pulmonary vasodilator and intravenously administered almitrine, a selective pulmonary vasoconstrictor, have been shown to...
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.
Topics: Administration, Inhalation; Almitrine; Analysis of Variance; Blood Pressure; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Heart; Humans; Injections, Intravenous; Lactates; Lung; Male; Middle Aged; Nitric Oxide; Oxygen; Positive-Pressure Respiration; Prospective Studies; Pulmonary Artery; Respiratory Distress Syndrome; Respiratory System Agents; Shock, Septic; Vascular Resistance; Vasoconstrictor Agents; Vasodilator Agents
PubMed: 9847266
DOI: 10.1164/ajrccm.158.6.9804066 -
Anesthesiology Nov 1998The partition of pulmonary blood flow between normal and shunting zones is an important determinant of oxygen tension in arterial blood (PaO2). The authors hypothesized... (Clinical Trial)
Clinical Trial
BACKGROUND
The partition of pulmonary blood flow between normal and shunting zones is an important determinant of oxygen tension in arterial blood (PaO2). The authors hypothesized that the combination of inhaled nitric oxide (iNO) and almitrine infusion might have additional effects related to their pharmacologic properties to improve PaO2. Such a combination was tested in patients with hypoxia caused by focal lung lesions, distinct from the acute respiratory distress syndrome.
METHODS
Fifteen patients with hypoxic focal lung lesions despite optimal therapy were included and successively treated with (1) 5 ppm iNO, (2) low-dose almitrine infusion (5.5 +/- 1.7 microg x kg(-1) min(-1)) during iNO, and (3) almitrine infusion alone (with NO turned off). Then iNO was reintroduced and we studied the effect of the coadministration in reducing the fractional concentration of oxygen in inspired gas (FI(O2)) and positive end-expiratory pressure (PEEP) levels. Changes in blood gases and pulmonary and systemic hemodynamics were measured.
RESULTS
Systemic hemodynamic variables remained stable in all protocol conditions. Use of iNO improved arterial oxygenation and decreased intrapulmonary shunt. Almitrine similarly improved PaO2 but increased pulmonary artery pressure and right atrial pressure. Coadministration of iNO and almitrine improved PaO2 compared with each drug alone and with control. All patients responded (that is, they had at least a +30% increase in PaO2) to this coadministration. When the drug combination was continued, FI(O2) and PEEP could be reduced over 8 h. The hospital mortality rate was 33% and unrelated to hypoxia.
CONCLUSIONS
In hypoxemic focal lung lesions, iNO or low-dose almitrine markedly improved PaO2 to a similar extent. Furthermore, the coadministration amplified the PaO2 increase at a level that allowed reductions in FI(O2) and PEEP levels.
Topics: Administration, Inhalation; Adult; Aged; Almitrine; Blood Pressure; Cardiac Catheterization; Female; Humans; Hypoxia; Infusions, Intravenous; Lung Diseases; Male; Middle Aged; Nitric Oxide; Pulmonary Gas Exchange; Respiratory Function Tests; Respiratory System Agents
PubMed: 9822004
DOI: 10.1097/00000542-199811000-00016