Investigation into use of drugs preceding death from asthma.

Speizer, Frank E.; Doll, Richard; Heaf, P. J. D.; Strang, L. B.

doi:10.1136/bmj.1.5588.339

Cited by 315 publications

(91 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

mentioning

confidence: 99%

“…The increase in deaths has been attributed to excessive use of aerosols containing sympathomimetic amines, principally isoprenaline (Speizer, Doll, Heaf & Strang, 1968). In the study of Speizer, Doll, Heaf & Strang (1968) 150 out of 174 patients had been using bronchodilators shortly before death. As isoprenaline administered by inhalation is absorbed rapidly into the blood stream and affects the heart (Chamberlain, 1967), it has been suggested that the deaths in these asthmatic patients may result from sympathomimetic-induced cardiac arrhythmias for example ventricular tachycardia or fibrillation (Speizer, Doll, Heaf & Strang, 1968).…”

mentioning

confidence: 99%

“…In the study of Speizer, Doll, Heaf & Strang (1968) 150 out of 174 patients had been using bronchodilators shortly before death. As isoprenaline administered by inhalation is absorbed rapidly into the blood stream and affects the heart (Chamberlain, 1967), it has been suggested that the deaths in these asthmatic patients may result from sympathomimetic-induced cardiac arrhythmias for example ventricular tachycardia or fibrillation (Speizer, Doll, Heaf & Strang, 1968). This is speculation, for detailed studies have not been made in any of these patients.…”

mentioning

confidence: 99%

See 2 more Smart Citations

The cardio‐toxicity of isoprenaline during hypoxia

Collins¹,

McDevitt²,

Shanks³

et al. 1969

British J Pharmacology

104

View full text Add to dashboard Cite

The effects of the intravenous injection of isoprenaline on heart rate and arterial pressure has been studied in dogs artificially respired with room air or with 12% oxygen—88% nitrogen. In dogs breathing room air, isoprenaline in doses from 0.02 to 500 μg/kg increased heart rate and reduced arterial pressure. Ventricular fibrillation was produced in one out of three dogs given 250 μg/kg. This was the only dog breathing room air which was killed by isoprenaline. In dogs breathing room air the repeated intravenous injection at 5‐min intervals of 2.5 μg/kg increased heart rate and reduced arterial pressure. No ill effects were produced by six doses. In dogs respired with 12% oxygen—88% nitrogen the Pao2 was reduced from 84 to 38 mm Hg with no changes in Paco2. In these dogs death was produced by doses of isoprenaline which in dogs breathing room air produced normal responses. The fatal dose of isoprenaline (10–50 μg/kg) reduced heart rate and arterial and pulse pressures; sinus rhythm persisted until arterial pressure was less than 50 mm Hg. Ventricular fibrillation did not occur; death occurred from cardiac asystole. Death was produced in a similar way in dogs with hypoxaemia by giving four or five doses of isoprenaline (2.5 μg/kg) at 5‐min intervals or by two doses of 25 μg/kg. The final reduction in arterial pressure during a fatal response resulted from a reduction in cardiac contractility. These lethal effects of isoprenaline could be prevented by pretreatment with propranolol.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

The cardio‐toxicity of isoprenaline during hypoxia

Collins¹,

McDevitt²,

Shanks³

et al. 1969

British J Pharmacology

104

View full text Add to dashboard Cite

show abstract

“…Initially it was suggested 22 that it might result from sympathomimeticinduced cardiac arrhythmias, for example, ventricular tachycardia or fibrillation (Speizer et at, 1968). Subsequently one of the metabolites of isoprenaline was found to have 3-adrenoceptor blocking properties and it was thought that this might be harmful (Paterson, Conolly, Davies & Dollery, 1968) or that the heart might be sensitized to endogenous catecholamines by fluorinated hydrocarbons present in pressurized nebulizers (Taylor & Harris, 1970;Dollery, Draffan, Davies, Williams & Conolly, 1970).…”

Section: Introductionmentioning

confidence: 99%

“…The observed increase in mortality from asthma between 1960 and 1966, particularly in the younger age groups, has been attributed to the excessive use of aerosols containing sympathomimetic amines, principally isoprenaline (Speizer, Doll, Heaf & Strang, 1968), and appears to have been geographically related to areas in which highly concentrated pressurized aerosols of isoprenaline were available (Stolley, 1972). Recognition of this possible relationship between isoprenaline inhalation and sudden death, and more disciplined use of this type of preparation has resulted in a reversal of the trend (Inman & Adelstein, 1969).…”

Section: Introductionmentioning

confidence: 99%

Further Observations on the Cardiotoxicity of Isoprenaline During Hypoxia

McDevitt¹,

Shanks²,

Swanton³

1974

British J Pharmacology

View full text Add to dashboard Cite

In dogs respired with 10% oxygen: 90% nitrogen, only five out of 16 dogs survived repeated intravenous doses of isoprenaline (either 0.5 or 1.0 μg/kg) and only one out of six dogs survived repeated isoprenaline inhalations from a pressurized aerosol. In dogs respired with 15% oxygen: 85% nitrogen, five out of six dogs survived repeated intravenous doses of isoprenaline (2.5 μg/kg). The fatal response in these animals consisted of a fall in heart rate, arterial and pulse pressures. Sinus rhythm persisted even after the arterial pressure had fallen, though occasionally a slow A‐V nodal rhythm or irregular ventricular ectopic beats occurred. Ventricular fibrillation did not occur. Eight out of 10 dogs brought to the verge of a fatal response with 10% oxygen: 90% nitrogen and repeated doses of isoprenaline (2.5 μg/kg) were resuscitated by the administration of 100% oxygen and, when necessary, cardiac massage. A group of five dogs survived the combined effects of repeated doses of isoprenaline (2.5 μg/kg) and respiration with 10% oxygen: 90% nitrogen when the time interval between doses was 11 min, instead of the usual 5 minutes. Control of pH by infusion of sodium bicarbonate did not protect the dogs from the combined effects of hypoxia and repeated isoprenaline challenge. After a 60 min period of continuous isoprenaline infusion in dogs breathing room air, only one of 10 dogs survived artificial respiration with 10% oxygen: 90% nitrogen and repeated challenge with intravenous isoprenaline (1.0 μg/kg) at 5 min intervals. At the higher infusion levels of isoprenaline (0.1 and 1.0 μg kg−1 min−1), two dogs out of four died after the hypoxic mixture was started but before any isoprenaline challenge was given. The possible relevance of these findings in dogs to the recently observed increase in mortality in young asthmatics is discussed.

show abstract

Reappraisal of the United Kingdom epidemic of fatal asthma

Speizer¹

1987

Archives of Internal Medicine

View full text Add to dashboard Cite

Investigation into use of drugs preceding death from asthma.

Cited by 315 publications

References 4 publications

The cardio‐toxicity of isoprenaline during hypoxia

The cardio‐toxicity of isoprenaline during hypoxia

Further Observations on the Cardiotoxicity of Isoprenaline During Hypoxia

Reappraisal of the United Kingdom epidemic of fatal asthma

Contact Info

Product

Resources

About