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PubMed1999

A critical comparison of the dose delivery characteristics of four alternative inhalation devices delivering salbutamol: pressurized metered dose inhaler, Diskus inhaler, Diskhaler inhaler, and Turbuhaler inhaler.

Salbutamol is a short-acting beta 2 agonist which is effective as a rescue therapy in the treatment of asthma. This study uses in vitro test methods to compare the capability of four alternative devices to deliver an accurate and precise dose of salbutamol. It is demonstrated that the conventional metered dose inhaler (MDI) achieves excellent accuracy and precision in dose delivery. Additionally, it is the most efficient inhaler in terms of generating in-vitro a fine particle fraction from the dose. A spacer device has been shown to further enhance the dosing characteristics. When tested over a wide range of inspiratory air flow rates, the Diskus (GlaxoWellcome, Hertfordshire, UK) has comparable accuracy and precision to the MDI tested at 60 L/min, and it offers an advantage over two alternative dry powder inhalers (DPIs), delivering a more consistent dose across the range of flow rates tested and being more efficient at generating a fine particle fraction than either Turbuhaler (Astra, Lund, Sweden) or Diskhaler (GlaxoWellcome) at both 28 and 60 L/min inspiratory flow rates. Diskus, Diskhaler, Ventolin, Volumatic, and Rotadisk are trademarks of the GlaxoWellcome Group of companies. The Accuhaler is the alternative to the Diskus in those countries where the Diskus trademark is not available. Inspiryl and Turbuhaler are trademarks of the Astra Group of companies.

Administration, Inhalation↗
PubMed2004

Aerosol deposition in the human respiratory tract breathing air and 80:20 heliox.

Aerosol mixing resulting from turbulent flows is thought to be an important mechanism of deposition in the upper respiratory tract (URT). Since turbulence levels are a function of gas density, the use of a low density carrier gas would be expected to reduce deposition in the URT. We measured aerosol deposition in the respiratory tract of 8 healthy subjects using both air and heliox, a low density gas mixture containing 80% helium and 20% oxygen, as the carrier gas. The subjects breathed 0.5, 1, and 2 microm-diameter monodisperse polystyrene latex particles from a reservoir at a constant flow rate (approximately 450 mL/sec) and tidal volume (approximately 900 mL). Aerosol concentration and flow rate were measured at the mouth using a photometer and a pneumotachograph, respectively. Deposition was 17.0%, 20.3%, and 38.9% in air and 16.8%, 18.5%, and 36.9% in heliox for 0.5; 1, and 2 microm-diameter particles, respectively. There was a small but statistically significant decrease in deposition when using heliox compared to air for 1 and 2 microm-diameter particles (p < 0.05). While it could not be directly measured from these data, it is likely that when breathing heliox instead of air, deposition is reduced in the URT and increased in the small airways and alveoli.

Adult↗
PubMed2005

Dose delivery characteristics of the AIR pulmonary delivery system over a range of inspiratory flow rates.

The purpose of this study was to evaluate the in vitro and in vivo dose delivery characteristics of the AIR pulmonary delivery system over a range of flow rates. A 5-mg placebo powder of engineered particles with low densities (<0.4 g/cc) and large geometric diameters (>5 microm) was delivered via a simple, capsule based, passive dry powder inhaler. The emitted dose, geometric and aerodynamic particle size distributions (aPSDs) were obtained over a range of flow rates (15-60 LPM). The in vitro results demonstrated improved powder dispersion with increasing flow rate through the inhaler. The in vivo dose delivery characteristics were obtained by gamma scintigraphy. Twelve healthy subjects performed the following three inhalation maneuvers: (i) a targeted peak inspiratory flow rate (PIFR) of 20 +/- 10 LPM, (ii) a deep comfortable inhalation, and (iii) a deep forced inhalation. PIFR and inhaled volume were obtained during the inhalation of the dose using a spirometer. In vivo dose delivery was characterized by high and reproducible emitted doses (mean = 87%; inter and intra-subject CV = 5%) and high lung deposition (mean = 51% of the total dose), with low inter and intra-subject CVs (18% and 13%, respectively) across a range of PIFRs (12-86 LPM). Lung deposition of the total dose was shown not to be dependent on PIFR by analysis of variance across the range of inspiratory flow rates (p = 0.29). This was due to the competing effects of smaller aPSDs, increased extrathoracic deposition and higher emitted doses with increasing PIFR. Fully characterizing the effect of inspiratory flow rate requires analysis of the therapeutic response, as well as in vitro dose delivery and lung deposition.

Analysis of Variance↗
PubMed1984

Atropine increases inspiratory flow during enflurane anaesthesia after pethidine premedication.

The effects of atropine i.v. on inspired volume and occlusion pressure were measured in three groups of patients. Group PE received premedication with pethidine 50 mg and promethazine 12.5 mg i.m., and anaesthesia was provided by 2% enflurane in 67% nitrous oxide. Group TE received temazepam 20 mg orally for premedication and similar anaesthesia. Group TH received temazepam premedication and 1% halothane in 67% nitrous oxide. Atropine 0.02 mg kg-1 i.v. increased significantly the inspiratory flow in the first 1 s of inspiration, and this effect was greater in the group that received pethidine (9% increase in flow). However, occlusion pressure did not change, and minute volume was not altered. The results suggest that atropine increases inspiratory flow after pethidine premedication without increasing the force developed during inspiration, possibly by bronchodilatation.

Adult↗
PubMed2001

Inspiratory timing during anaesthesia: a model of cardioventilatory coupling.

We describe a simple model of cardioventilatory coupling in which a hypothetical inspiratory pacemaker is stimulated by a signal related to cardiac action. At suitable values for the control variables (cardiac signal magnitude, heart rate, inspiratory pacemaker rate and inspiratory rate variability), the model was found to: (1) replicate all clinically described patterns of coupling; (2) predict variations in these described patterns and new patterns which were subsequently found in clinical time series; (3) simulate variations in clinically observed breathing frequency variations associated with each coupling pattern; (4) simulate the clinically observed distribution of coupling patterns between heart rate and breathing frequency; (5) explain the invariability of coupling below a critical heart rate/breathing frequency ratio; and (6) simulate the changes in breathing frequency and transitions between coupling patterns from the heart rate time series of human subjects. Although cardioventilatory coupling causes complex breathing rate irregularities during anaesthesia, these are readily explained by three variables, heart rate, intrinsic breathing frequency, and the strength of their interaction. This simple model, along with clinical observations of cardioventilatory coupling may provide a useful non-invasive method to study the respiratory central pattern generator.

Anesthesia, General↗
PubMed1994

Central respiratory activity in rapid eye movement sleep: augmenting and late inspiratory cells [corrected].

The activities of 15 augmenting and 11 late inspiratory cells were studied in wakefulness, nonrapid eye movement (NREM) and rapid eye movement (REM) sleep in adult cats. All but one of each cell type were significantly more active in REM than in NREM sleep or relaxed wakefulness, indicating that central respiratory drive is increased in REM sleep. A negative correlation between the discharge rates of augmenting and late inspiratory cells and the durations of inspirations was characteristic of REM sleep. Although augmenting and late inspiratory activity increased in REM sleep, respiratory efforts in REM sleep were as likely to be lower than those in NREM sleep as they were to be greater. Thus, unknown factors can counteract the increased central drive. There was a positive correlation between the discharge rate of a cell on breath n and on breath n + 1, indicating that processes with a long time constant control respiratory drive in REM sleep. It is proposed that REM-specific reticular cells drive the respiratory oscillator and its output cells to produce the patterns of breathing in REM sleep.

Animals↗
PubMed2001

Effect of sleep position and sleep stage on the collapsibility of the upper airways in patients with sleep apnea.

Collapsibility of the upper airways has been identified as an important pathogenic factor in obstructive sleep apnea (OSA). Objective measures of collapsibility are pharyngeal critical pressure (Pcrit) and resistance of the upstream segment (Rus). To systematically determine the effects of sleep stage and body position we investigated 16 male subjects suffering from OSA. We compared the measures in light sleep, slow-wave sleep, REM sleep and supine vs. lateral positions. The pressure-flow relationship of the upper airways has been evaluated by simultaneous readings of maximal inspiratory airflow (Vimax) and nasal pressure (p-nCPAP). With two-factor repeated measures ANOVA on those 7 patients which had all 6 situations we found a significant influence of body position on Pcrit (p<0.05) whereas there was no significant influence of sleep stage and no significant interaction between body position and sleep stage. When comparing the body positions Pcrit was higher in the supine than in the lateral positions. During light sleep Pcrit decreased from 0.6 +/- 0.8 cm H2O (supine) to -2.2 +/- 3.6 cm H2O (lateral) (p<0.01), during slow-wave sleep Pcrit decreased from 0.3 +/- 1.4 cm H2O (supine) to -1.7 +/- 2.6 (lateral) (p<0.05) and during REM sleep it decreased from 1.2 +/- 1.5 cm H2O to -2.0 +/- 2.2 cm H2O (p<0.05). Changes in Rus revealed no body position nor sleep-stage dependence. Comparing the different body positions Rus was only significantly higher in the lateral position during REM sleep (p<0.05). The results indicate that collapsibility of the upper airways is not mediated by sleep stages but is strongly influenced by body position. As a consequence lower nCPAP pressure is needed during lateral positions compared to supine positions.

Adult↗
PubMed2003

Prediction of inspiratory flow shapes during sleep with a mathematic model of upper airway forces.

STUDY OBJECTIVES: To predict the airflow dynamics during sleep using a mathematic model that incorporates a number of static and dynamic upper airway forces, and to compare the numerical results to clinical flow data recorded from patients with sleep-disordered breathing on and off various treatment options. DESIGN: Upper airway performance was modeled in virtual subjects characterized by parameter settings that describe common combinations of risk factors predisposing to upper airway collapse during sleep. The treatments effect were induced by relevant changes of the initial parameter values. SETTING: Computer simulations at our website (http://www.utu.fi/ml/sovmat/bio/). PARTICIPANTS: Risk factors considered in the simulation settings were sex, obesity, pharyngeal collapsibility, and decreased phasic activity of pharyngeal muscles. INTERVENTIONS: The effects of weight loss, pharyngeal surgery, nasal continuous positive airway pressure, and respiratory stimulation on the inspiratory flow characteristics were tested with the model. MEASUREMENTS AND RESULTS: Numerical predictions were investigated by means of 3 measurable inspiratory airflow characteristics: initial slope, total volume, and flow shape. The model was able to reproduce the inspiratory flow shape characteristics that have previously been described in the literature. Simulation results also supported the observations that a multitude of factors underlie the pharyngeal collapse and, therefore, certain medical therapies that are effective in some conditions may prove ineffective in others. CONCLUSIONS: A mathematic model integrating the current knowledge of upper airway physiology is able to predict individual treatment responses. The model provides a framework for designing novel and potentially feasible treatment alternatives for sleep-disordered breathing.

Arousal↗
PubMed2001

The effects of thoracic epidural analgesia with bupivacaine 0.25% on ventilatory mechanics in patients with severe chronic obstructive pulmonary disease.

UNLABELLED: Optimal analgesia is important after thoracotomy in pulmonary-limited patients to avoid pain-related pulmonary complications. Thoracic epidural anesthesia (TEA) can provide excellent pain relief. However, potential paralysis of respiratory muscles and changes in bronchial tone might be unfavorable in patients with end-stage chronic obstructive pulmonary disease (COPD). Therefore, we evaluated the effect of TEA on maximal inspiratory pressure, pattern of breathing, ventilatory mechanics, and gas exchange in 12 end-stage COPD patients. Pulmonary resistance, work of breathing, dynamic intrinsic positive end-expiratory pressure, and peak inspiratory and expiratory flow rates were evaluated by assessing esophageal pressure and airflow. An increase in minute ventilation (7.50 +/- 2.60 vs 8.70 +/- 2.10 L/min; P = 0.04) by means of increased tidal volume (0.46 +/- 0.16 vs 0.53 +/- 0.14 L/breath; P = 0.003) was detected after TEA. These changes were accompanied by an increase in peak inspiratory flow rate (0.48 +/- 0.17 vs 0.55 +/- 0.14 L/s; P = 0.02) and a decrease in pulmonary resistance (20.7 +/- 9.9 vs 16.6 +/- 8.1 cm H(2)O. L(-1). s(-1); P = 0.02). Peak expiratory flow rate, dynamic intrinsic positive end-expiratory pressure, work of breathing, PaO(2), and maximal inspiratory pressure were unchanged (all P > 0.50). We conclude that TEA with bupivacaine 0.25% can be used safely in end-stage COPD patients. IMPLICATIONS: Thoracic epidural anesthesia with bupivacaine 0.25% does not impair ventilatory mechanics and inspiratory respiratory muscle strength in severely limited chronic obstructive pulmonary disease patients. Thus, thoracic epidural anesthesia can be used safely in patients with end-stage chronic obstructive pulmonary disease.

Adult↗
PubMed1975

Train-of-four nerve stimulation in the management of prolonged neuromuscular blockade following succinylcholine.

Four patients, all possessing an atypical form of plasma cholinesterase, developed prolonged paralysis following succinylcholine administration. The clinical management of all four cases was facilitated by monitoring the train-of-four stimulus. All patients showed marked "fade" of the train-of-four ratio, the initial ratios of the fourth to the first twitches being 50 per cent or less, indicating variable degrees of nondepolarizing neuromuscular blockade. Reversal of paralysis with anticholinesterase agents was completely successful in three cases, but only partially effective in the fourth because of the probable presence of a mixture of both depolarizing block and nondepolarizing block. In such a situation, caution in the interpretation of the train-of-four ratio is necessary, since this test measures only the nondepolarizing component of the block. Whether or not reversal with anticholinesterase drugs is attempted, clinical estimates of neuromuscular function, such as head lift, vital capacity, and inspiratory force, must be carefully correlated with train-of-four values. If reversal is attempted, the brief action of edrophonium provides a useful clinical trial.

Adolescent↗
PubMed1986

Effect of halothane on diaphragmatic muscle function in pentobarbital-anesthetized dogs.

The mechanism underlying the decrease in minute ventilation (VE) observed under halothane anesthesia was investigated in nine spontaneously breathing dogs. Anesthesia was induced with pentobarbital sodium and was maintained with halothane. Inspired fraction of halothane (FIhal) was increased every 30 min, from 0.005 to 0.02. VE decreased from 8.1 +/- 0.9 to 4.8 +/- 0.4 l . min-1 (P less than 0.001), as FIhal increased from 0 to 0.02. This resulted from a decrease in both mean inspiratory flow (VT/TI) and the duty ratio (TI/TTOT). Transdiaphragmatic pressure (Pdi) and the integrated electrical activity of both hemidiaphragms (Edi) were measured during normal breathing, and during breathing against closed airways (P0di, E0di), in order to obtain an index of the inspiratory neuromuscular output of the diaphragm. With increasing FIhal, there was a significant decrease in Pdi, P0di, Edi, and E0di. The authors measured Pdi and Edi generated during supramaximal stimulation of the two phrenic nerves (PSdi, Esdi) at frequencies of 10, 20, 50, and 100 Hz, in order to eliminate in this decrease the role played by a decrease in the neural drive to breathing. PSdi and ESdi decreased significantly with increasing FIhal, and had not returned to the control values 30 min after discontinuation of halothane administration. The authors conclude that, in pentobarbital-anesthetized dogs, halothane is responsible for a diaphragmatic dysfunction, which may be located either at the neuromuscular junction, on the contractile processes of the muscle, or on both, and for a decrease in the activation time of the inspiratory muscles. Both of these effects contribute to the decrease in VE observed under halothane anesthesia.

Anesthesia↗
PubMedDate not supplied

Kinematic analysis of patients with spinal muscular atrophy during spontaneous breathing and mechanical ventilation.

Patients with infantile spinal muscular atrophy develop pectus excavatum along with a severe restrictive syndrome as a result of failure to expand the upper chest wall and lungs because of intercostal muscle weakness. By using an automatic motion analyzer to provide three-dimensional computer analyses of images sampled at 25 Hz, 9 spinal muscular atrophy Type II patients and 13 controls underwent kinematic analysis of thoracoabdominal movements partitioned into the upper thorax, lower thorax, and abdominal volume compartments. The analyses were performed during spontaneous breathing for the controls and during spontaneous breathing and while using mechanically assisted ventilation for the patients. Vital capacity, maximum inspiratory pressures, and nocturnal oxyhemoglobin saturation and transcutaneous carbon dioxide tensions were also measured for the patients. The kinematic data demonstrated a paradoxical ventilatory pattern for the spontaneously breathing SMA patients with the following inspiratory volume changes: upper thorax, -6.4+/-9.6%; lower thorax, 7.3+/-15.8%; abdominal, 99.1+/-21.3%. During mechanical ventilation, the compartmental volume changes were as follows: upper thorax, 13.5+/-6%; lower thorax, 13.7+/-7.9%; abdominal, 72.7+/-9.3%. This kinematic pattern is comparable with that seen in spontaneously breathing normal subjects. We conclude that mechanical ventilation can normalize kinematic volume changes during alveolar ventilation and that this might help deter loss of thoracic compliance caused by the chronic hypoventilation of the upper thoracic compartments. Kinematic analysis may be helpful for choosing the ventilation parameters to optimize therapeutic benefits.

Biomechanical Phenomena↗
PubMed1980

Influence of varying inspired oxygen tensions on the pulmonary venous admixture (shunt) of mechanically ventilated patients.

Pulmonary venous admixture (shunt) was measured in 10 mechanically ventilated patients with respiratory failure at varying oxygen tensions. All patients manifested a drop in pulmonary shunt as FIO2 was increased from 0.21 to 0.4. Further increase in FIO2 led to a gradual increase in the calculated venous admixture. The clinical significance of the conventional measurements of pulmonary shunt at FIO2 = 1.0 is questionable because of the marked effect of FIO2 on pulmonary shunt. Consequently, shunt measurements should be performed with the clinically useful FIO2.

Humans↗
PubMed1992

Increased sensitivity to mechanical ventilation after surfactant inactivation in young rabbit lungs.

OBJECTIVES: To study the individual and combined effects of surfactant inactivation and mechanical ventilation on pulmonary microvascular permeability and lung compliance. DESIGN: Prospective, controlled trial. An isolated, perfused, lung model of surfactant inactivation and mechanical ventilation at 15, 30, and 45 cm H2O peak inspiratory pressure was developed in young (4 to 6 wks) New Zealand white rabbits. SETTING: Laboratory of a university-affiliated medical school. MEASUREMENTS AND MAIN RESULTS: Isolated, perfused lungs were prepared for measurement of the capillary filtration coefficient before and after one of four interventions: instillation of dioctyl succinate, a surfactant inactivator, without ventilation (group 1); ventilation without dioctyl succinate at 15, 30, or 45 cm H2O peak inspiratory pressure (group 2); ventilation after dioctyl succinate pretreatment at 15, 30, or 45 cm H2O peak inspiratory pressure (group 3); and control lungs without dioctyl succinate or ventilation (group 4). A significant increase in the capillary filtration coefficient was noted after dioctyl succinate treatment alone, after ventilation alone at 45 cm H2O peak inspiratory pressure, and after dioctyl succinate plus ventilation at 15, 30, and 45 cm H2O peak inspiratory pressure. Dioctyl succinate plus ventilation produced a significantly greater increase in the capillary filtration coefficient than ventilation alone at 15 and 45 cm H2O peak inspiratory pressure. CONCLUSIONS: These data suggest that ventilation after surfactant inactivation is more injurious to the pulmonary microvasculature than ventilation alone, and that generalized lung overdistention is not the primary mechanism for microvascular injury in the diseased, noncompliant lung. The increases seen in the capillary filtration coefficient in postventilated surfactant inactivated lungs, even at low-ventilation pressures, suggest that low peak inspiratory pressures do not overdistend the dioctyl succinate-treated lung.

Animals↗