CASE REPORTS
POSSffiLE ASSOCIATION OF BENZALKONIUM CHLORIDE IN NEBULIZER SOLUTIONS WITH RESPIRATORY ARREST Michel Boucher, Myrella T. Roy, and John Henderson
OBJECTIVE: To report a case of possible associationof benzalkonium chloride in nebulizer solutions with respiratory arrest and to review the involvementof various preservativeagents in paradoxical bronchoconstrictive reactions. DATASOURC&: Reference articles, case reports, and editorialsare identifiedin the text.
tients by triggering paradoxical bronchoconstriction.' However, we can fmd no reference in the literature to respiratory arrest as an iatrogenic event solely attributable to administration of nebulized albuterol or ipratropium solutions containing a preservative.
DATASYNTHESIS: Many pharmacologicagents are availablefor
nebulization. In addition to the active drug, these nebulizer solutions may contain preservatives.We describe a case of respiratoryarrest in a 64-year-old man following nebulizationtherapy with albuterol and ipratropiumsolutions.These solutions contain benzalkonium chloride as a preservative. We are aware of only one report describingtwo deaths associated with such a severe reaction attributableto nebulizationtherapy. However, many reports of milder paradoxicalbronchoconstriction are available in the medical literature. CONCLUSIONS: Clinicians should be aware of the possibilityof paradoxicalbronchoconstrictive reactions when patients are treated with nebulizedbronchodilators.
AnnPharmacother 1992;26:772-4. NEBULIZAnON is a cornmon treatment modality in asthma and chronic obstructive pulmonary disease. Many pharmacologie agents are available in nebulizer solutions, including beta, adrenoreceptor agonists, anticholinergic drugs, sodium cromoglycate, and corticosteroids. In addition to the active drug, nebulizer solutions may contain preservative agents, such as benzalkonium chloride (BAC) and sulfite derivatives. These preservatives may cause paradoxical bronchoconstriction, varying in severity from mild to severe, and affecting both adults and children.P We describe a case of respiratory arrest following nebulization therapy with albuterol and ipratropium. These two nebulizer solutions contain 100 llg/mL (0.01 %) and 250 llg/mL (0.025%) of BAC, respectively. This preservative has been associated with a significant drop in the forced expiratory volume in one second (FEVl ) when administered in nebulizer solution.' The use of nebulizer solutions was reported to have contributed to the deaths of two pa-
MICHEL BOUCHER, B.Pharm., D.H.P., is a Clinical Pharmacist, Pulmonary and InternalMedicine;MYRELLA T. ROY, Pharm.D.,is the AssistantDirectorof Pharmacy,ClinicalServices; andJOHN HENDERSON, M.B.,FRCPC,is the Headof PulmonaryService,OttawaGeneral Hospital,Ottawa,Ontario,Canada.Reprints: Michel Boucher, B.Pharm., D.H.P., Pulmonary and Internal Medicine, Ottawa General Hospital, 501 Smyth Rd., Ottawa, Ontario, Canada, KIH 8L6.
772 • The Annals ofPharmacotherapy • 1992June, Volume 26
CASE REPORT
A 64-year-old man was admitted to the OnawaGeneral Hospital because of an exacerbation of chronic obstructive airway disease. Hispresenting symptoms wereincreasing shortness of breathand productive cough. The week prior to admission,he developed slightfever, increasing cough with thicksputum, and chesttightness. He had been using home oxygen for six months and had been a 50 pack-year cigarette smoker before quitting one year prior to the current admission. His history was otherwiseunremarkable, The patienthad no knowndrug allergies. Medications on admission were: prednisone 10mg/dpo; potassium chloride 8 mmol/dpo; sustained-release theophylline 350 mg po bid; furosemide40 mg/d po; and albuterol and ipratropium metered-dose inhalers, two puffseachqid. His serum theophylline concentrationon admission was 84 umol/l, and his arterial blood gases on 28% oxygen were pH 7.44, PaCOz 48.0 mm Hg, PaOz 75.3 mm Hg, and bicarbonate (HC03 ) 32.2 mmol/L,These results were similarto values obtainedfive monthsprior to the currentadmission. The FEV, and the peak expiratoryflow rate on admissionwere 17 and 9% of the predicted values, respectively (Table 1). The chest X-ray showedchangesof severebullousemphysema, but no evidence of pneumonia or pulmonary congestion. The patientwas startedon intermittent albuterol 1 mL mixed in 2 mL of ipratropium via wet nebulized aerosol. The patient was exposedto 600 ~g of BAC per treatment. The drug combinationwas administered q1-2h initially, thenwas changed to q4h because the patient was complainingof increaseddifficulty in breathing after treatments. Intravenoussteroids and oral ampicillinalso wereincluded in the regimen. The patientinitially improved and early discharge was anticipated.However, as mentioned previously, he beganto complain of increasedshortness of breath after each nebulizedtreatment. Posttreatment bedside flow rates showed some deterioration comparedwith pretreatment values (Table 1).This information wasnot relayedto the medical housestaff. Thatnight, he wasgiven albuterol and ipratropium treatments at 2300 and 0330 by the respiratory technologist, as ordered. No othermedication was administered until0400, whenthe patientwas found unresponsive on the floor by the nursing staff. He was noted to be densely cyanotic but was makingsomerespiratory efforts on his own.He was immediately bag-ventilated. Blood pressure was 150/100 mm Hg and the electrocardiogram showed atrial fibrillation with a ventricular rate of 200 beats/min. Chestexamination revealed bilateral decreased air en-
try with a prolonged expiratory phase. At this time, arterial blood gases were pH 6.8, PaCOz 183 mmHg, PaOz 92 mmHg, and HCOl 29 mrnol/L, The patient was given verapamil to control the heart rate and diazepam before intubation. He was transferred to the intensive care unit for further management. Administration of a1buterol and ipratropium was resumed as nebulizer solutions for the first two treatments and then via metered-dose inhalers, to avoid further exposure to the now-suspect preservative agent. The next day, the patient was much improved and was extubated. After two days of observation, he was returned to the ward where he continued to improve on treatment with a1buterol and ipratropium metered-dose inhalers with use of a spacer. He was discharged in satisfactory condition on day II.
The decline in this patient's condition is consistent with the occurrence of bronchoconstriction following the use of nebulizer solutions. We believe that clinicians must be aware of the possibility of paradoxical bronchoconstriction when patients are treated with nebulized bronchodilators. Any patient complaining of increased shortness of breath after receiving a nebulized treatment should be believed because there may be dramatic consequences, as illustrated by this case. Paradoxical bronchoconstriction has been attributed to a number of possible causes, including idiosyncratic reaction to the bronchodilators and bronchospastic effect of preservatives contained in nebulizer solutions. I Considering the time course of the event, the amount of preservative present in the nebulized solutions, and the lack of reaction to the drugs administered via metered-dose inhalation, this case is suggestive of a preservative-induced severe paradoxical bronchoconstriction. However, confirmation of this causal relationship would have required a controlled rechallenge. Two classes of preservative agents have been mostly involved in these reactions: the sulfite derivatives (including sodium metabisulfite and sodium bisulfite) and BAC.2,3,8 Sulfite derivatives are most likely to cause adverse reactions and in solution have been shown to release sulfur dioxide. It has been suggested that the sulfur dioxide molecule is responsible for the bronchospastic effect of sulfite derivatives by augmenting mast-eell mediator release or by stimulating sensory irritant nerves in the bronchial mucosa.2.3 The bronchospastic effect of sodium metabisulfite is inhibited by nedocromil sodium, a mast-cell stabilizing
agent.' Benzalkonium chloride, the most frequent additive to nebulizer solutions, may also cause bronchoconstriction by releasing spasmogenic mediators from mast cells within the bronchial wall. I ,2,6" Pretreatment with cromolyn sodium has been reported to prevent BAC-induced bronchoconstriction.v- There also is speculation that BAC may stimulate cholinergic and noncholinergic nerves in the airways.' Other additives have been thought to have bronchospastic effect, such as EDTA (ethylenediaminetetraacetic acid), although firm confirmation is stilllacking. I •3,6,9,l o Beasleyet al." and Zhang et al.' have documented doseresponse curves for BAC-induced bronchospasm. The lowest doses of BAC to drop FEV I by 20 percent from baseline were 159 and 1241lg, respectively.' Our patient was exposed to doses substantially higher than these minimal amounts. The ideal nebulizer preparation should be preservativefree and packaged in unit-dose containers. Until such products are commercially available and in routine use, clinicians should remain alert to the possibility of adverse reactions to preservative agents in nebulizer solutions. ~ We are very grateful to Michel A. Drouin. M.D., for his critical review of our manuscript.
References I. Worthington I. Bronchoconstriction due to benzalkonium chloride in the nebu1izer solutions. CanJ HospPharm 1989;42:165-6. 2. Beasley R, Rafferty P, Holgate ST. Adverse reactions to the non-drug constituents of nebulizer solutions. Br J Clin PharmacoI1988;25:2837. 3. Nebulizers and paradoxical bronchoconstriction (editorial). Lancet 1988;2:202. 4. Beasley R, Rafferty P, Holgate S. Benzalkonium chloride and bronchoconstriction (letter). Lancet 1986;2:1227. 5. Menendez R, Lowe RS, Keresey S. Benzalkonium chloride and bronchoconstriction. J AllergyCUn Immuno/1989;84:272-4. 6. Beasley CRW, Rafferty P, Holgate ST. Bronchoconstrictionproperties of preservatives in ipratropium bromide (Atrovent) nebulizer solution.
BrMedJ 1987;294:1197-8. 7. Zhang YG, Wright WJ, Tam WK, Nguyen-Dang TH, Salome CM, Woolcock AJ. Effect of inhaled preservativeson asthmatic subjects.II. Benzalkoniumchloride. Am RevRespirDis 1990;141:1405-8. 8. Twarog FJ, Leung DYM. Anaphylaxis to a component of isoetharine (sodium bisulfi.te).JAMA 1982;248:2030-1. 9. Rafferty P, Beasley R, Holgate ST. Comparison of the efficacy of preservative-freeipratropium bromide and Atrovent nebu1izer solution.
Thorax 1988;43:446-50.
Table 1. Predicted Versus Measured Flow Rates in Patient Experiencing Paradoxical Bronchoconstriction DATE{fIME
FVC
FEVl
PEFR
FLOW RATES
(L)
(L)
(Lis)
predicted measured measured measured measured measured
4.34 2.61 2.35 2.86 2.80 1.13
3.46 0.58 0.49 0.70 0.70 0.74
10.28 0.89 0.60 1.18 0.67 1.12
measured measured
2.99 2.17
0.71 0.67
1.18 0.77
10. O'Callaghan C, Milner AD, Swarbrick A. Paradoxical bronchoconstriction in wheezing infants after nebulized preservative-free iso-osmolar ipratropium bromide. Br Med J 1989;299:1433-4.
5/6/90 16:35 (pre) 17:10 (post) 19:00 (post)" 21:00 (pre) 21:20 (post)
5n/90 10:10 (pre) 10:30 (post)"
"The respiratory technologist noted thai the patient complained of increased breathlessness after treatment. FEV l = forced expiratory volume in one second; FVC = forced vital capacity; PEFR = peak expiratory flow rate.
EXIRACfO
Reportar el caso de una posible asociaci6n entre la administraei6n de c1oruro de benzalconio en soluciones pulverizadoras y el desarrollo de paro respiratorio. Tambien, revisar el involucramiento de varios agentes preservativos en el desarrollo de reacciones broncoconstrictivas parad6xicas. OBJETIVO:
FUENTES DE INFORMACION:
Articulos de referencia, reportes de casos
clfnicos, y editoriales. SINTFSIS: Muchos agentes farmacol6gicos se encuentran disponibles en forma de aerosol. Ademas del agente activo, estas soluciones pulverizadas pueden contener agentes preservativos. Este articulo describe el caso de un paciente de 64 afios de edad que present6 para
The AnnalsofPharmacotherapy • 1992 June, Volume 26 •
773
respiratoriodespues de recibir terapia por inhalaci6ncon salbutamol (albuterol) y solucionesde ipratropium.Estas solucionescontienen c1oruro de benzalconiocomo preservativo.Los autores afirman conocer un solo repone de dos casos de muerte atribufdosa esta reacci6nadversa severa despues de la administraei6nde terapia por inhalaci6n. Sin embargo, muchos casos de broncoconstricci6n parad6xica leve han sido descritosen la literaturamedica CONCLUSIONES: Los medicos deberfanestar al tanto del posibledesarrollo de este tipo reaccionesadversas en pacientes tratadoscon broncodiIatadores por inhalaci6n. ENCARNACI6N C. suAREz
RESUME
Rapporter un cas d'association possibleentre un arret respiratoireet la presencede chlorure de benzalkoniumdans les solutionspour nebulisation, Reviser les divers agents de conservation impliquesdans les reactions bronchoconstrictrices paradoxales.
OBJECTIF:
774 •
Articlesde references, rapportsde cas et editoriauxidentifiesdans Ie texte.
SOURCES DES OONNEES:
Plusieursagents pharmacologiques sont disponiblespour la nebulisation, En plus de la substanceactive,ces solutionspour nebuliseurpeuvent egalementcontenirdes agents de conservation. Nous decrivonsun cas d'arret respiratoirechez un homme de 64 ans, a la suite d'un traitementpar nebulisation avec des solutions de salbutamolet d'ipratropium. Ces solutionscontiennentdu chlorurede benzalkoniumcomme agent de conservation. A notre connaissance, iI n' existe qu'un seul cas decrivantIe deces de deux patients,suite 11 une reactionaussi serieuse,Par contre, de nombreuxcas de reactions bronchoconstrictrices moins severes ont paru dans la litterature medicale, SYNIlIESE DES OONNEES:
Les cliniciensdevraientetre conscientsde la possibilitede reactionsbronchoconstrictrices paradoxaleslorsque des patients sont traites avec des bronchodiIatateurs administrespar nebulisation,
CONCLUSIONS:
The AnnalsofPharmacotherapy • 1992 June, Volume 26
MICHELBOUCHER
POSSffiLE ASSOCIATION OF BENZALKONIUM CHLORIDE IN NEBULIZER SOLUTIONS WITH RESPIRATORY ARREST Michel Boucher, Myrella T. Roy, and John Henderson
OBJECTIVE: To report a case of possible associationof benzalkonium chloride in nebulizer solutions with respiratory arrest and to review the involvementof various preservativeagents in paradoxical bronchoconstrictive reactions. DATASOURC&: Reference articles, case reports, and editorialsare identifiedin the text.
tients by triggering paradoxical bronchoconstriction.' However, we can fmd no reference in the literature to respiratory arrest as an iatrogenic event solely attributable to administration of nebulized albuterol or ipratropium solutions containing a preservative.
DATASYNTHESIS: Many pharmacologicagents are availablefor
nebulization. In addition to the active drug, these nebulizer solutions may contain preservatives.We describe a case of respiratoryarrest in a 64-year-old man following nebulizationtherapy with albuterol and ipratropiumsolutions.These solutions contain benzalkonium chloride as a preservative. We are aware of only one report describingtwo deaths associated with such a severe reaction attributableto nebulizationtherapy. However, many reports of milder paradoxicalbronchoconstriction are available in the medical literature. CONCLUSIONS: Clinicians should be aware of the possibilityof paradoxicalbronchoconstrictive reactions when patients are treated with nebulizedbronchodilators.
AnnPharmacother 1992;26:772-4. NEBULIZAnON is a cornmon treatment modality in asthma and chronic obstructive pulmonary disease. Many pharmacologie agents are available in nebulizer solutions, including beta, adrenoreceptor agonists, anticholinergic drugs, sodium cromoglycate, and corticosteroids. In addition to the active drug, nebulizer solutions may contain preservative agents, such as benzalkonium chloride (BAC) and sulfite derivatives. These preservatives may cause paradoxical bronchoconstriction, varying in severity from mild to severe, and affecting both adults and children.P We describe a case of respiratory arrest following nebulization therapy with albuterol and ipratropium. These two nebulizer solutions contain 100 llg/mL (0.01 %) and 250 llg/mL (0.025%) of BAC, respectively. This preservative has been associated with a significant drop in the forced expiratory volume in one second (FEVl ) when administered in nebulizer solution.' The use of nebulizer solutions was reported to have contributed to the deaths of two pa-
MICHEL BOUCHER, B.Pharm., D.H.P., is a Clinical Pharmacist, Pulmonary and InternalMedicine;MYRELLA T. ROY, Pharm.D.,is the AssistantDirectorof Pharmacy,ClinicalServices; andJOHN HENDERSON, M.B.,FRCPC,is the Headof PulmonaryService,OttawaGeneral Hospital,Ottawa,Ontario,Canada.Reprints: Michel Boucher, B.Pharm., D.H.P., Pulmonary and Internal Medicine, Ottawa General Hospital, 501 Smyth Rd., Ottawa, Ontario, Canada, KIH 8L6.
772 • The Annals ofPharmacotherapy • 1992June, Volume 26
CASE REPORT
A 64-year-old man was admitted to the OnawaGeneral Hospital because of an exacerbation of chronic obstructive airway disease. Hispresenting symptoms wereincreasing shortness of breathand productive cough. The week prior to admission,he developed slightfever, increasing cough with thicksputum, and chesttightness. He had been using home oxygen for six months and had been a 50 pack-year cigarette smoker before quitting one year prior to the current admission. His history was otherwiseunremarkable, The patienthad no knowndrug allergies. Medications on admission were: prednisone 10mg/dpo; potassium chloride 8 mmol/dpo; sustained-release theophylline 350 mg po bid; furosemide40 mg/d po; and albuterol and ipratropium metered-dose inhalers, two puffseachqid. His serum theophylline concentrationon admission was 84 umol/l, and his arterial blood gases on 28% oxygen were pH 7.44, PaCOz 48.0 mm Hg, PaOz 75.3 mm Hg, and bicarbonate (HC03 ) 32.2 mmol/L,These results were similarto values obtainedfive monthsprior to the currentadmission. The FEV, and the peak expiratoryflow rate on admissionwere 17 and 9% of the predicted values, respectively (Table 1). The chest X-ray showedchangesof severebullousemphysema, but no evidence of pneumonia or pulmonary congestion. The patientwas startedon intermittent albuterol 1 mL mixed in 2 mL of ipratropium via wet nebulized aerosol. The patient was exposedto 600 ~g of BAC per treatment. The drug combinationwas administered q1-2h initially, thenwas changed to q4h because the patient was complainingof increaseddifficulty in breathing after treatments. Intravenoussteroids and oral ampicillinalso wereincluded in the regimen. The patientinitially improved and early discharge was anticipated.However, as mentioned previously, he beganto complain of increasedshortness of breath after each nebulizedtreatment. Posttreatment bedside flow rates showed some deterioration comparedwith pretreatment values (Table 1).This information wasnot relayedto the medical housestaff. Thatnight, he wasgiven albuterol and ipratropium treatments at 2300 and 0330 by the respiratory technologist, as ordered. No othermedication was administered until0400, whenthe patientwas found unresponsive on the floor by the nursing staff. He was noted to be densely cyanotic but was makingsomerespiratory efforts on his own.He was immediately bag-ventilated. Blood pressure was 150/100 mm Hg and the electrocardiogram showed atrial fibrillation with a ventricular rate of 200 beats/min. Chestexamination revealed bilateral decreased air en-
try with a prolonged expiratory phase. At this time, arterial blood gases were pH 6.8, PaCOz 183 mmHg, PaOz 92 mmHg, and HCOl 29 mrnol/L, The patient was given verapamil to control the heart rate and diazepam before intubation. He was transferred to the intensive care unit for further management. Administration of a1buterol and ipratropium was resumed as nebulizer solutions for the first two treatments and then via metered-dose inhalers, to avoid further exposure to the now-suspect preservative agent. The next day, the patient was much improved and was extubated. After two days of observation, he was returned to the ward where he continued to improve on treatment with a1buterol and ipratropium metered-dose inhalers with use of a spacer. He was discharged in satisfactory condition on day II.
The decline in this patient's condition is consistent with the occurrence of bronchoconstriction following the use of nebulizer solutions. We believe that clinicians must be aware of the possibility of paradoxical bronchoconstriction when patients are treated with nebulized bronchodilators. Any patient complaining of increased shortness of breath after receiving a nebulized treatment should be believed because there may be dramatic consequences, as illustrated by this case. Paradoxical bronchoconstriction has been attributed to a number of possible causes, including idiosyncratic reaction to the bronchodilators and bronchospastic effect of preservatives contained in nebulizer solutions. I Considering the time course of the event, the amount of preservative present in the nebulized solutions, and the lack of reaction to the drugs administered via metered-dose inhalation, this case is suggestive of a preservative-induced severe paradoxical bronchoconstriction. However, confirmation of this causal relationship would have required a controlled rechallenge. Two classes of preservative agents have been mostly involved in these reactions: the sulfite derivatives (including sodium metabisulfite and sodium bisulfite) and BAC.2,3,8 Sulfite derivatives are most likely to cause adverse reactions and in solution have been shown to release sulfur dioxide. It has been suggested that the sulfur dioxide molecule is responsible for the bronchospastic effect of sulfite derivatives by augmenting mast-eell mediator release or by stimulating sensory irritant nerves in the bronchial mucosa.2.3 The bronchospastic effect of sodium metabisulfite is inhibited by nedocromil sodium, a mast-cell stabilizing
agent.' Benzalkonium chloride, the most frequent additive to nebulizer solutions, may also cause bronchoconstriction by releasing spasmogenic mediators from mast cells within the bronchial wall. I ,2,6" Pretreatment with cromolyn sodium has been reported to prevent BAC-induced bronchoconstriction.v- There also is speculation that BAC may stimulate cholinergic and noncholinergic nerves in the airways.' Other additives have been thought to have bronchospastic effect, such as EDTA (ethylenediaminetetraacetic acid), although firm confirmation is stilllacking. I •3,6,9,l o Beasleyet al." and Zhang et al.' have documented doseresponse curves for BAC-induced bronchospasm. The lowest doses of BAC to drop FEV I by 20 percent from baseline were 159 and 1241lg, respectively.' Our patient was exposed to doses substantially higher than these minimal amounts. The ideal nebulizer preparation should be preservativefree and packaged in unit-dose containers. Until such products are commercially available and in routine use, clinicians should remain alert to the possibility of adverse reactions to preservative agents in nebulizer solutions. ~ We are very grateful to Michel A. Drouin. M.D., for his critical review of our manuscript.
References I. Worthington I. Bronchoconstriction due to benzalkonium chloride in the nebu1izer solutions. CanJ HospPharm 1989;42:165-6. 2. Beasley R, Rafferty P, Holgate ST. Adverse reactions to the non-drug constituents of nebulizer solutions. Br J Clin PharmacoI1988;25:2837. 3. Nebulizers and paradoxical bronchoconstriction (editorial). Lancet 1988;2:202. 4. Beasley R, Rafferty P, Holgate S. Benzalkonium chloride and bronchoconstriction (letter). Lancet 1986;2:1227. 5. Menendez R, Lowe RS, Keresey S. Benzalkonium chloride and bronchoconstriction. J AllergyCUn Immuno/1989;84:272-4. 6. Beasley CRW, Rafferty P, Holgate ST. Bronchoconstrictionproperties of preservatives in ipratropium bromide (Atrovent) nebulizer solution.
BrMedJ 1987;294:1197-8. 7. Zhang YG, Wright WJ, Tam WK, Nguyen-Dang TH, Salome CM, Woolcock AJ. Effect of inhaled preservativeson asthmatic subjects.II. Benzalkoniumchloride. Am RevRespirDis 1990;141:1405-8. 8. Twarog FJ, Leung DYM. Anaphylaxis to a component of isoetharine (sodium bisulfi.te).JAMA 1982;248:2030-1. 9. Rafferty P, Beasley R, Holgate ST. Comparison of the efficacy of preservative-freeipratropium bromide and Atrovent nebu1izer solution.
Thorax 1988;43:446-50.
Table 1. Predicted Versus Measured Flow Rates in Patient Experiencing Paradoxical Bronchoconstriction DATE{fIME
FVC
FEVl
PEFR
FLOW RATES
(L)
(L)
(Lis)
predicted measured measured measured measured measured
4.34 2.61 2.35 2.86 2.80 1.13
3.46 0.58 0.49 0.70 0.70 0.74
10.28 0.89 0.60 1.18 0.67 1.12
measured measured
2.99 2.17
0.71 0.67
1.18 0.77
10. O'Callaghan C, Milner AD, Swarbrick A. Paradoxical bronchoconstriction in wheezing infants after nebulized preservative-free iso-osmolar ipratropium bromide. Br Med J 1989;299:1433-4.
5/6/90 16:35 (pre) 17:10 (post) 19:00 (post)" 21:00 (pre) 21:20 (post)
5n/90 10:10 (pre) 10:30 (post)"
"The respiratory technologist noted thai the patient complained of increased breathlessness after treatment. FEV l = forced expiratory volume in one second; FVC = forced vital capacity; PEFR = peak expiratory flow rate.
EXIRACfO
Reportar el caso de una posible asociaci6n entre la administraei6n de c1oruro de benzalconio en soluciones pulverizadoras y el desarrollo de paro respiratorio. Tambien, revisar el involucramiento de varios agentes preservativos en el desarrollo de reacciones broncoconstrictivas parad6xicas. OBJETIVO:
FUENTES DE INFORMACION:
Articulos de referencia, reportes de casos
clfnicos, y editoriales. SINTFSIS: Muchos agentes farmacol6gicos se encuentran disponibles en forma de aerosol. Ademas del agente activo, estas soluciones pulverizadas pueden contener agentes preservativos. Este articulo describe el caso de un paciente de 64 afios de edad que present6 para
The AnnalsofPharmacotherapy • 1992 June, Volume 26 •
773
respiratoriodespues de recibir terapia por inhalaci6ncon salbutamol (albuterol) y solucionesde ipratropium.Estas solucionescontienen c1oruro de benzalconiocomo preservativo.Los autores afirman conocer un solo repone de dos casos de muerte atribufdosa esta reacci6nadversa severa despues de la administraei6nde terapia por inhalaci6n. Sin embargo, muchos casos de broncoconstricci6n parad6xica leve han sido descritosen la literaturamedica CONCLUSIONES: Los medicos deberfanestar al tanto del posibledesarrollo de este tipo reaccionesadversas en pacientes tratadoscon broncodiIatadores por inhalaci6n. ENCARNACI6N C. suAREz
RESUME
Rapporter un cas d'association possibleentre un arret respiratoireet la presencede chlorure de benzalkoniumdans les solutionspour nebulisation, Reviser les divers agents de conservation impliquesdans les reactions bronchoconstrictrices paradoxales.
OBJECTIF:
774 •
Articlesde references, rapportsde cas et editoriauxidentifiesdans Ie texte.
SOURCES DES OONNEES:
Plusieursagents pharmacologiques sont disponiblespour la nebulisation, En plus de la substanceactive,ces solutionspour nebuliseurpeuvent egalementcontenirdes agents de conservation. Nous decrivonsun cas d'arret respiratoirechez un homme de 64 ans, a la suite d'un traitementpar nebulisation avec des solutions de salbutamolet d'ipratropium. Ces solutionscontiennentdu chlorurede benzalkoniumcomme agent de conservation. A notre connaissance, iI n' existe qu'un seul cas decrivantIe deces de deux patients,suite 11 une reactionaussi serieuse,Par contre, de nombreuxcas de reactions bronchoconstrictrices moins severes ont paru dans la litterature medicale, SYNIlIESE DES OONNEES:
Les cliniciensdevraientetre conscientsde la possibilitede reactionsbronchoconstrictrices paradoxaleslorsque des patients sont traites avec des bronchodiIatateurs administrespar nebulisation,
CONCLUSIONS:
The AnnalsofPharmacotherapy • 1992 June, Volume 26
MICHELBOUCHER
