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Salbutamol by pressure-packed aerosol and by intermittent positive pressure ventilation in chronic obstructive bronchitis
Br. 3. Dis. Chest (1978) 72, 122
SALBUTAMOL BY PRESSURE-PACKED AEROSOL AND BY INTERMITTENT POSITIVE PRESSURE VENTILATION IN CHRONIC OBSTRUCTIVE BRONCHITIS NORBERT BEREND, JANICE WEBSTER AND GRAHAM Respiratory
Unit, Repatriation General Hospital, New South Wales, Australia
E. MARLIN Concord,
Summary The forced expiratory volume in one second (FEV1) response to salbutamol administered by pressure-packed aerosol 200 pg, and intermittent positive pressure ventilation (IPPV), 5 and 10 mg, was determined in 60 patients with chronic bronchitis with airway obstruction. The bronchodilator response to salbutamol by IPPV was greater than by pressure-packed aerosol only in patients with severe airways obstruction and little additional benefit was gained with the 10 mg dose.
INTRODUCTION
/3-adrenoceptor stimulating drugs administered by pressure-packed aerosol (PPA) or intermittent positive pressure ventilation (IPPV) are widely used in the treatment of reversible airways obstruction in asthma and chronic obstructive bronchitis. The object of this study was to compare the bronchodilator response after salbutamol by PPA and IPPV in patients with the clinical diagnosis of chronic bronchitis.
Patients and Methods Sixty male hospital patients (age range 48-87 years) who had previously recovered from an acute infective exacerbation of chronic bronchitis and had been stabilized on maintenance treatment were selected for this study. All patients except two had smoked for many years in the past or immediately before admission to hospital. The MRC questionnaire on respiratory symptoms (1960) was applied to each patient and all fulfilled the Medical Research Council (1956) criteria as well as having a clinical diagnosis of chronic bronchitis. The patients were currently receiving treatment with tablet (14) and aerosol (5) corticosteroids, disodium cromoglycate (5), salbutamol by inhalation (51) and oral theophylline (38). Salbutamol, 200 pg by PPA (2 x 100 pg inhalations), 5 mg (1 ml of 0.5% solution and 1 ml of saline) or 10 mg (2 ml of 0.5% solution) by IPPV, was separately administered in a single-blind balanced randomized trial on three consecutive mornings. Salbutamol by IPPV was delivered by a Bird Mark 8 respirator (settings: pressure, 15 cm water; flow rate, lo-15 ; sensitivity, 15) for a period until complete nebulization of the dose occurred (5-7 minutes). All treatments were supervised and administered by a physiotherapist. Forced expiratory volume in one second (FEV1) was measured with a dry spirometer (Vitalograph) before, and 15 and 30 minutes after
Salbutamol by Inhalation
in Chronic Bronchitis
123
each treatment, the highest of three readings on each occasion used for comparisons. It was necessary for there to be less than 15% variation between the baseline FEVr readings on each treatment day. Salbutamol and theophylline treatments were withdrawn for 12 hours before each study day, but tablet and aerosol corticosteroids and disodium cromoglycate were continued at their maintenance doses. The informed consent of all patients was obtained. The results were submitted to statistical analysis using student’s t-test (group and paired).
RESULTS There was no significant difference between the control, baseline FEVr values before salbutamol 200 pg by PPA (mean + S.E. 1.13 f 0.07 litres), 5 mg by IPPV (mean? S.E. 1.13 f 0.07 litres) and 10 mg by IPPV (mean f S.E. 1.12 f 0.07 litres). The mean f S.E. o/o increases in FEVl from control for all patients were 15.1 & 1.5%, 21.2 + 2.3% and 22.7 f 2.5% for salbutamol 200 pg by PPA, 5 and 10 mg by IPPV respectively, none differing significantly from each other. The control FEVr values for each patient were expressed as the percentage of their predicted normal values and were divided into three groups (A, less than 30%, 17 patients; B, 30-50°h, 21 patients; C, more than SO%, 22 patients) in order to relate the bronchodilator response with the severity of initial airways obstruction (Table I). Seventeen patients showed greater than 30% improvement to one or more treatments, and nine of these gave a history consistent with the diagnosis of asthma. Table I. FEVl and %FEVl increases from control in 60 patients after salbutamol Salbutamol
Group A
Group B
Group C
FEVl increase from control (mean + S.E.) (Zitres) 200 pg by PPA 0.13 f 0.03 5 mg by IPPV 0.19 + 0.05 10 mg by IPPV 0.21 f 0.05X
0.17 + 0.02 0.21 +0.02x 0.23 +0.03-f
0.16 f 0.02 0.25 f 0.05 0.23 f 0.04
“/” FEVl increase from contro12yyz:4S.E.) 200 cLg by PPA 5 mg by IPPV 29:7 + 6:s 10 mg by IPPV 33.5 + 7.1”
15.3-tl.6 19.8 * 1.7” 22.8 + 2.4-f
10.4f 1.3 16.0 f 3.1 14.2 f 2.3
(%)
Control FEVr as percentage of predicted normal: Group A (17 patients) Group B (21 patients) 30-50% ; Group C (22 patients) > 50%. Comparison of IPPV and PA: *P < 0.05 ; tP < 0.01.
< 300/, ;
DISCUSSION Salbutamol by IPPV was shown to be more effective than by PPA in patients with more severe airways obstruction when the FEVl improvement was expressed as a percentage of the initial recording. Choo-Kang and Grant (1975) d emonstrated in patients said to have chronic asthma that the superiority of 10 mg salbutamol by IPPV over 200 pg by PPA was greatest in those with the lowest pre-treatment FEVr (< 0.75 litre). Webber achieved with salet al. (1974), h owever, showed no difference in bronchodilatation butamol delivered by IPPV and Wright’s nebulizer in patients said to have asthma. Also, Goldberg and Cherniack (1965) were unable to demonstrate any difference between
124
N. Berend, J. Webster and G. E. Marlin
bronchodilator treatment by a hand nebulizer and IPPV in patients said to have emphysema. The improved response to IPPV administration in our groups A and B (with the lowest FEVr) may be dose-related. Only lo-15% of the original salbutamol dose by IPPV is deposited in the lungs, although a greater proportion of the drug available to the patient may be deposited in the lung by IPPV than by PPA administration (Shenfield et al. 1973). Thus 10 mg salbutamol by IPPV would be equivalent to at least 10 to 15 lOO-pg inhalations by PPA. However, multiple dosing by PPA may be ineffectively managed in patients with severe dyspnoea and poor inspiratory effort. Our study suggests that salbutamol doses above 5 mg by IPPV will provide little additional improvement. We conclude that the delivery of salbutamol by IPPV may provide additional benefit to patients with chronic obstructive bronchitis only when the airways obstruction is severe. Otherwise, no advantage has been demonstrated with IPPV over the more conventional and cheaper pressure packed aerosol for the delivery of bronchodilators by inhalation in chronic obstructive bronchitis. REFERENCES CHOO-KANG, Y. F. J. & GRANT, I. W. B. (1975) Comparison of two methods of administering bronchodilator aerosol to asthmatic patients. Br. med. J 2, 119. GOLDBERG, I. & CHERNIACK, R. M. (1965) The effect of nebulized bronchodilator delivered with and without IPPB on ventilatory function in chronic obstructive emphysema. Am. Rev.
resp. Dis. 91, 13. MEDICAL RESEARCH COUNCIL (1965) Definition and classification of chronic bronchitis for clinical and epidemiological purposes. Lancet i, 775. SHENFIELD, G. M., EVANS, M. E., WALKER, S. R. & PATERSON, J. W. (1973) The fate of nebulized salbutamol (albuterol) administered by intermittent positive pressure respiration to asthmatic patients. Am. Rev. resp. Dis. 108, 501. WEBBER, B. A., SHENFIELD, G. M. & PATERSON, J. W. (1974) A comparison of three different techniques for giving nebulized albuterol to asthmatic patients. Am. Rev. resp. Dis. 109, 293.
SALBUTAMOL BY PRESSURE-PACKED AEROSOL AND BY INTERMITTENT POSITIVE PRESSURE VENTILATION IN CHRONIC OBSTRUCTIVE BRONCHITIS NORBERT BEREND, JANICE WEBSTER AND GRAHAM Respiratory
Unit, Repatriation General Hospital, New South Wales, Australia
E. MARLIN Concord,
Summary The forced expiratory volume in one second (FEV1) response to salbutamol administered by pressure-packed aerosol 200 pg, and intermittent positive pressure ventilation (IPPV), 5 and 10 mg, was determined in 60 patients with chronic bronchitis with airway obstruction. The bronchodilator response to salbutamol by IPPV was greater than by pressure-packed aerosol only in patients with severe airways obstruction and little additional benefit was gained with the 10 mg dose.
INTRODUCTION
/3-adrenoceptor stimulating drugs administered by pressure-packed aerosol (PPA) or intermittent positive pressure ventilation (IPPV) are widely used in the treatment of reversible airways obstruction in asthma and chronic obstructive bronchitis. The object of this study was to compare the bronchodilator response after salbutamol by PPA and IPPV in patients with the clinical diagnosis of chronic bronchitis.
Patients and Methods Sixty male hospital patients (age range 48-87 years) who had previously recovered from an acute infective exacerbation of chronic bronchitis and had been stabilized on maintenance treatment were selected for this study. All patients except two had smoked for many years in the past or immediately before admission to hospital. The MRC questionnaire on respiratory symptoms (1960) was applied to each patient and all fulfilled the Medical Research Council (1956) criteria as well as having a clinical diagnosis of chronic bronchitis. The patients were currently receiving treatment with tablet (14) and aerosol (5) corticosteroids, disodium cromoglycate (5), salbutamol by inhalation (51) and oral theophylline (38). Salbutamol, 200 pg by PPA (2 x 100 pg inhalations), 5 mg (1 ml of 0.5% solution and 1 ml of saline) or 10 mg (2 ml of 0.5% solution) by IPPV, was separately administered in a single-blind balanced randomized trial on three consecutive mornings. Salbutamol by IPPV was delivered by a Bird Mark 8 respirator (settings: pressure, 15 cm water; flow rate, lo-15 ; sensitivity, 15) for a period until complete nebulization of the dose occurred (5-7 minutes). All treatments were supervised and administered by a physiotherapist. Forced expiratory volume in one second (FEV1) was measured with a dry spirometer (Vitalograph) before, and 15 and 30 minutes after
Salbutamol by Inhalation
in Chronic Bronchitis
123
each treatment, the highest of three readings on each occasion used for comparisons. It was necessary for there to be less than 15% variation between the baseline FEVr readings on each treatment day. Salbutamol and theophylline treatments were withdrawn for 12 hours before each study day, but tablet and aerosol corticosteroids and disodium cromoglycate were continued at their maintenance doses. The informed consent of all patients was obtained. The results were submitted to statistical analysis using student’s t-test (group and paired).
RESULTS There was no significant difference between the control, baseline FEVr values before salbutamol 200 pg by PPA (mean + S.E. 1.13 f 0.07 litres), 5 mg by IPPV (mean? S.E. 1.13 f 0.07 litres) and 10 mg by IPPV (mean f S.E. 1.12 f 0.07 litres). The mean f S.E. o/o increases in FEVl from control for all patients were 15.1 & 1.5%, 21.2 + 2.3% and 22.7 f 2.5% for salbutamol 200 pg by PPA, 5 and 10 mg by IPPV respectively, none differing significantly from each other. The control FEVr values for each patient were expressed as the percentage of their predicted normal values and were divided into three groups (A, less than 30%, 17 patients; B, 30-50°h, 21 patients; C, more than SO%, 22 patients) in order to relate the bronchodilator response with the severity of initial airways obstruction (Table I). Seventeen patients showed greater than 30% improvement to one or more treatments, and nine of these gave a history consistent with the diagnosis of asthma. Table I. FEVl and %FEVl increases from control in 60 patients after salbutamol Salbutamol
Group A
Group B
Group C
FEVl increase from control (mean + S.E.) (Zitres) 200 pg by PPA 0.13 f 0.03 5 mg by IPPV 0.19 + 0.05 10 mg by IPPV 0.21 f 0.05X
0.17 + 0.02 0.21 +0.02x 0.23 +0.03-f
0.16 f 0.02 0.25 f 0.05 0.23 f 0.04
“/” FEVl increase from contro12yyz:4S.E.) 200 cLg by PPA 5 mg by IPPV 29:7 + 6:s 10 mg by IPPV 33.5 + 7.1”
15.3-tl.6 19.8 * 1.7” 22.8 + 2.4-f
10.4f 1.3 16.0 f 3.1 14.2 f 2.3
(%)
Control FEVr as percentage of predicted normal: Group A (17 patients) Group B (21 patients) 30-50% ; Group C (22 patients) > 50%. Comparison of IPPV and PA: *P < 0.05 ; tP < 0.01.
< 300/, ;
DISCUSSION Salbutamol by IPPV was shown to be more effective than by PPA in patients with more severe airways obstruction when the FEVl improvement was expressed as a percentage of the initial recording. Choo-Kang and Grant (1975) d emonstrated in patients said to have chronic asthma that the superiority of 10 mg salbutamol by IPPV over 200 pg by PPA was greatest in those with the lowest pre-treatment FEVr (< 0.75 litre). Webber achieved with salet al. (1974), h owever, showed no difference in bronchodilatation butamol delivered by IPPV and Wright’s nebulizer in patients said to have asthma. Also, Goldberg and Cherniack (1965) were unable to demonstrate any difference between
124
N. Berend, J. Webster and G. E. Marlin
bronchodilator treatment by a hand nebulizer and IPPV in patients said to have emphysema. The improved response to IPPV administration in our groups A and B (with the lowest FEVr) may be dose-related. Only lo-15% of the original salbutamol dose by IPPV is deposited in the lungs, although a greater proportion of the drug available to the patient may be deposited in the lung by IPPV than by PPA administration (Shenfield et al. 1973). Thus 10 mg salbutamol by IPPV would be equivalent to at least 10 to 15 lOO-pg inhalations by PPA. However, multiple dosing by PPA may be ineffectively managed in patients with severe dyspnoea and poor inspiratory effort. Our study suggests that salbutamol doses above 5 mg by IPPV will provide little additional improvement. We conclude that the delivery of salbutamol by IPPV may provide additional benefit to patients with chronic obstructive bronchitis only when the airways obstruction is severe. Otherwise, no advantage has been demonstrated with IPPV over the more conventional and cheaper pressure packed aerosol for the delivery of bronchodilators by inhalation in chronic obstructive bronchitis. REFERENCES CHOO-KANG, Y. F. J. & GRANT, I. W. B. (1975) Comparison of two methods of administering bronchodilator aerosol to asthmatic patients. Br. med. J 2, 119. GOLDBERG, I. & CHERNIACK, R. M. (1965) The effect of nebulized bronchodilator delivered with and without IPPB on ventilatory function in chronic obstructive emphysema. Am. Rev.
resp. Dis. 91, 13. MEDICAL RESEARCH COUNCIL (1965) Definition and classification of chronic bronchitis for clinical and epidemiological purposes. Lancet i, 775. SHENFIELD, G. M., EVANS, M. E., WALKER, S. R. & PATERSON, J. W. (1973) The fate of nebulized salbutamol (albuterol) administered by intermittent positive pressure respiration to asthmatic patients. Am. Rev. resp. Dis. 108, 501. WEBBER, B. A., SHENFIELD, G. M. & PATERSON, J. W. (1974) A comparison of three different techniques for giving nebulized albuterol to asthmatic patients. Am. Rev. resp. Dis. 109, 293.