Bronchodilator delivery by metered-dose inhaler in mechanically ventilated COPD patients: influence of end-inspiratory pause

Abstract

The delivery of bronchodilators with metered-dose inhalers (MDI) in mechanically ventilated patients has received considerable interest in recent years [1][2][3][4][5]. It has been shown that MDI adapted to the inspiratory line of the ventilator using a spacer device are as effective as nebulizers, despite a significantly lower dose of bronchodilator given by the MDI [1][2][3][4][5]. A spacer device is thought to be fundamental in order to demonstrate the efficacy of the bronchodilatory therapy given by MDI [1][2][3][4][5]. Studies that delivered bronchodilators with MDI directly to the endotracheal tube failed to demonstrate any beneficial effect, even after the administration of high doses of bronchodilators [6]. The use of MDI has several advantages over the nebulizer, such as reduced cost, ease of administration, less personnel time, reliability of dosing and a lower risk of contamination [7][8][9][10].The technique of administration of bronchodilators in mechanically ventilated patients using an MDI and a spacer is an important factor that determines the efficacy of this therapy. Proper timing of the drug delivery, adequate tidal volumes, relatively low inspiratory flows and application of end-inspiratory pause (EIP) (breath-hold) are some of the variables that have been suggested to enhance drug delivery to target sites [4,5]. In particular, EIP of 3-5 s duration has been thought to be an important factor in the success of MDI therapy [1,11]. However, although breath-holding is a prerequisite for optimal drug delivery in spontaneously breathing nonintubated patients, the effect of EIP on the efficacy of MDI therapy in mechanically ventilated patients is not known. The purpose of the present study was, therefore, to examine the effect of EIP on the bronchodilation induced by β 2 -agonists administered with an MDI and a spacer, in a homogeneous group of mechanically ventilated patients with chronic obstructive pulmonary disease (COPD). MethodsTwelve patients (9 males and 3 females) with COPD, requiring mechanical ventilation to manage acute respiratory Twelve patients with COPD, mechanically ventilated on volume-controlled mode, were prospectively randomized to receive six puffs of salbutamol (100 µg·puff -1 ) either with or without EIP of 5 s duration. Salbutamol was administered with an MDI adapted to the inspiratory limb of the ventilator circuit using an aerosol cloudenhancer spacer. After a 6 h wash-out, patients were crossed over to receive salbutamol by the alternative mode of administration. Static and dynamic airway pressures, minimum (Rmin) and maximum (Rmax) airflow resistance, the difference between Rmax and Rmin (∆R), static end-inspiratory respiratory system compliance (Cst,rs) and cardiac frequency (fC) were measured before and at 15, 30 and 60 min after salbutamol administration.Salbutamol caused a significant decrease in dynamic and static airway pressures, Rmin and Rmax. These changes were not influenced by application of EIP and were evident at 15, 30 and 60 min after salbutamol. With and ...

Bronchodilator delivery by metered-dose inhaler in mechanically ventilated COPD patients: influence of flow pattern

“…It was further shown that the response was evident even when salbutamol was given in relatively low doses and not influenced by the inspiratory flow/time profile during drug delivery. Independent of the dose of salbutamol, DR remained relatively constant throughout the study, indicating that salbutamol acted by dilating the central airways, in line with previous observations [3,13,14]. Although expiratory resistance was not measured in the present study, it was most probably decreased by salbutamol, as indicated by the significant reduction in PEEPi and end-inspiratory static plateau pressure, indirect indices of dynamic hyperinflation.…”

“…It is possible that salbutamol, against a background of relatively low airway resistance, was not able to reduce Rint further. A similar observation has been made previously [13].…”

“…these recommendations are based mainly on aerosol delivery data [11,12], which may not reflect drug bronchodilator effect. Indeed, in recent studies, it was shown that neither application of a 5 s end-inspiratory pause nor increasing the VT, strategies which probably enhanced drug delivery [4,5,11,12], augmented the bronchodilator effect of six puffs salbutamol [13,14]. The current study demonstrated that, at constant VT and inspiratory time, changing the inspiratory flow/time profile did not have any effect on salbutamol-induced bronchodilation, given via MDI and spacer.…”

“…These suggestions, however, are based on in vitro studies using models of mechanical ventilation. Indeed it was recently demonstrated in mechanically ventilated patients with chronic obstructive pulmonary disease (COPD) that application of an end-inspiratory pause time of 5 s or a 50% increase in VT when bronchodilators were administered in adequate doses did not have any additional bronchodilator effect [13,14]. These studies raise the issue that ventilator settings may not be a critical factor in bronchodilation.…”

Effect of Albuterol on Expiratory Resistance in Mechanically Ventilated Patients

“…1 The effect of bronchodilators in mechanically ventilated patients is commonly evaluated by the decrease in end-inspiratory airway resistance and in intrinsic PEEP. [2][3][4] End-inspiratory airway resistance and intrinsic PEEP are easily measured at the bedside in ventilated patients, without spontaneous respiratory efforts, with end-inspiratory and end-expiratory occlusions. 5 It is important to recognize however, that inspiratory and expiratory resistance differ, and it is the expiratory resistance that affects the development of dynamic hyperinflation.…”