Diethyl Ether의 불순물에 관한 연구

Abstract

[한글]

Study on the Impurities in Anesthetic Diethyl Ether

Wha Sung Chung

Department of Medical Science, The Graduate School, Yonsei University

The impurities of diethyl ether are mainly acetic aldehyde and ether peroxide.

Other impurities are sulfuric acid, alcohol, sulphur dioxide, mercaptane and ethyl

ester. It was believed that these impurities are produced during production and

storage.

When we use ether containing impurities, inhalation of excessive peroxide can

cause salivation, profuse bronchial secretion, lung edema and pneumonia.

Excessive aldehyde also irritates the mucous membrane and can cause lacrimation,

photophobia, conjunctivitis, an oppressive feeling of the chest, severe cough,

headache, unconsciousness, bronchitis and pneumonia.

It is well known that the deterioration of ether is favoured by contact with air,

heat and sunlight. There are two opposite opinions on reuse of ether.

Baskerville(1910) claimed that it should not be used for anesthesia twenty-four

hours after the container is opened. However Harry and David Gold(1934) showed

that, in ordinary anesthetic ether cans which were opened many times and stoppered

with cork, the contents remaining pure by very delicate chemical tests for the

usual impurities, aldehyde and peroxide, during a period of months.

In order to measure the impurities of ether, four brands of ether for anesthesia

were randomly selected for analysis. Type of containers and date of production in

each group are as follows;

Group Ⅰ : So called Korean made ether, 140ml in brown bottle, one month old.

Group Ⅱ : Mallinckrodt Chemical Works, made in U.S.A., 1/4Lb can.

Group Ⅲ : May & Baker LTD., made in england, 100g(140ml) can.

Group Ⅳ : Showa, so called Japan made ether, 160ml in brown bottle, fourteen

months old in three samples and four years and six months old in another three

samples.

They were analysed by chemical tests for peroxide, aldehyde and acetic acid just

after the container were opened(sero day) and one, two, four, six and eight days.

Ethyl alcohol was analysed by gas chromatography.

The result was as follows;

Ether peroxide; limit value for U.S.P. is 7.1 microgram/10ml ether(0.025 mg of

hydrogen peroxide/25gm ether). In group Ⅰ and Ⅲ, they were within this value from

zero to eight days but in group Ⅱ and Ⅳ, they exceeded this value already on zero

day.

In all group, they increased gradually day by day up to eight days.

Aldehyde; limit value in U.S.P. is 0.007mg/20ml ether(formaldehyde 0.0005%). In

group Ⅰ, there was nothing on zero day but after twenty-four hours it exceeded the

control value and increased day by day up to eight days.

In groups Ⅱ, Ⅲ and Ⅳ, they exceeded this value already on zero day, and

increased day by day up to eight days but were below maximum allowance

concentration for U.S.P.

Acidity; The incidence was slightly increased day by day up to eight days but all

were within normal range.

By gaschromatography, analysis showed 4% ethyl alcohol in group Ⅲ and Ⅳ.

On the other hand, to ascertain the interrelationship between the production of

impurities and the existence of alcohol or H₂O₂ in ether, 3% alcohol(group A), 6%

alcohol(group B), H₂O₂(600microgram%) (group C), and H₂O₂ with 3% alcohol

together(group D) were added to ether respectively.

In four groups, Immediately after one, two, four, six and eight days after the

containers were opened, they were analysed for peroxide, aldehyde and acidity.

Peroxide; This were increased in all groups just after adding, and increased

furthur day by day up to eight days when the increase was marked.

Especially in the group D, it increased sharply.

Aldehyde; It was increased in all groups just after adding, and thereafter

increased or decreased irregularly by day up to eight days by which time it had

increased markedly.

Acidity; It was increased in all groups up to one and/or two days and thereafter

decreased day by day up to eight days.

However none of the groups exceeded the limit value of 0.1ml of N/50 NaOH.

It was concluded that:

1. Impurities in ether for anesthesia are influenced by type of container for

storage, date of its production, and duration after container is opened.

2. ether for anesthesia should not be used for this purpose, if the original

container has been opened longer than twenty four hours.

3. The production of impurities in ether was influenced by the presence of

alcohol in ether.

4. It would be better to analyse the ether for impurities by chemical tests prior

to clinical use.

[영문]

The impurities of diethyl ether are mainly acetic aldehyde and ether peroxide.

Other impurities are sulfuric acid, alcohol, sulphur dioxide, mercaptane and ethyl ester. It was believed that these impurities are produced during production and storage.

When we use ether containing impurities, inhalation of excessive peroxide can cause salivation, profuse bronchial secretion, lung edema and pneumonia.

Excessive aldehyde also irritates the mucous membrane and can cause lacrimation, photophobia, conjunctivitis, an oppressive feeling of the chest, severe cough, headache, unconsciousness, bronchitis and pneumonia.

It is well known that the deterioration of ether is favoured by contact with air, heat and sunlight. There are two opposite opinions on reuse of ether.

Baskerville(1910) claimed that it should not be used for anesthesia twenty-four hours after the container is opened. However Harry and David Gold(1934) showed that, in ordinary anesthetic ether cans which were opened many times and stoppered

with cork, the contents remaining pure by very delicate chemical tests for the usual impurities, aldehyde and peroxide, during a period of months.

In order to measure the impurities of ether, four brands of ether for anesthesia were randomly selected for analysis. Type of containers and date of production in each group are as follows;

Group Ⅰ : So called Korean made ether, 140ml in brown bottle, one month old.

Group Ⅱ : Mallinckrodt Chemical Works, made in U.S.A., 1/4Lb can.

Group Ⅲ : May & Baker LTD., made in england, 100g(140ml) can.

Group Ⅳ : Showa, so called Japan made ether, 160ml in brown bottle, fourteen months old in three samples and four years and six months old in another three samples.

They were analysed by chemical tests for peroxide, aldehyde and acetic acid just after the container were opened(sero day) and one, two, four, six and eight days.

Ethyl alcohol was analysed by gas chromatography.

The result was as follows;

Ether peroxide; limit value for U.S.P. is 7.1 microgram/10ml ether(0.025 mg of hydrogen peroxide/25gm ether). In group Ⅰ and Ⅲ, they were within this value from zero to eight days but in group Ⅱ and Ⅳ, they exceeded this value already on zero

day.

In all group, they increased gradually day by day up to eight days.

Aldehyde; limit value in U.S.P. is 0.007mg/20ml ether(formaldehyde 0.0005%). In group Ⅰ, there was nothing on zero day but after twenty-four hours it exceeded the control value and increased day by day up to eight days.

In groups Ⅱ, Ⅲ and Ⅳ, they exceeded this value already on zero day, and increased day by day up to eight days but were below maximum allowance concentration for U.S.P.

Acidity; The incidence was slightly increased day by day up to eight days but all were within normal range.

By gaschromatography, analysis showed 4% ethyl alcohol in group Ⅲ and Ⅳ.

On the other hand, to ascertain the interrelationship between the production of impurities and the existence of alcohol or H₂O₂ in ether, 3% alcohol(group A), 6% alcohol(group B), H₂O₂(600microgram%) (group C), and H₂O₂ with 3% alcohol

together(group D) were added to ether respectively.

In four groups, Immediately after one, two, four, six and eight days after the containers were opened, they were analysed for peroxide, aldehyde and acidity.

Peroxide; This were increased in all groups just after adding, and increased furthur day by day up to eight days when the increase was marked.

Especially in the group D, it increased sharply.

Aldehyde; It was increased in all groups just after adding, and thereafter increased or decreased irregularly by day up to eight days by which time it had increased markedly.

Acidity; It was increased in all groups up to one and/or two days and thereafter decreased day by day up to eight days.

However none of the groups exceeded the limit value of 0.1ml of N/50 NaOH.

It was concluded that:

1. Impurities in ether for anesthesia are influenced by type of container for storage, date of its production, and duration after container is opened.

2. ether for anesthesia should not be used for this purpose, if the original container has been opened longer than twenty four hours.

3. The production of impurities in ether was influenced by the presence of alcohol in ether.

4. It would be better to analyse the ether for impurities by chemical tests prior to clinical use.