ACETONURIA FOLLOWING CHLOROFORM AND ETHER ANlflSTHESIA.

BY HELEN BALDWIN.

(From the Laboratory of Dr. C. A. Herter, New York.)

(Received for publication, November 20, 1905.)

The pronounced degenerative changes which may occur in the liver after chloroform narcosis were recognized as early as 1866 by Nothnagel,r and have been noted and carefully studied by a number of observers since his time. More recently the symptoms of these cases of chloroform poisoning have been studied by Guthrie? Stocker,3 Brewer,4 Brackett,s Kelly,6 and Bevan and Favill.7 These symptoms have been recognized as those of an acid intoxication and are described by Bevan and Favill as follows: “This symptom-complex consists of vomiting, restlessness, delirium, convulsions, coma, Cheyne-Stokes respira- tion, cyanosis, icterus in varying degree, and usually terminates in death.”

Out of twenty-eight cases of death following chloroform an- ssthesia and having these characteristic symptoms, which are noted in Bevan and Favill’s paper, the urine was tested in four instances for the presence of acetone and diacetic acid and these bodies were found. In another case there was noted an acetone- like odor to the breath, and in another leucin, tyrosin, and bile pigment were found in the urine.

A routine examination of the urine for acetone, in the cases of patients who had been anresthetized, was made by Greven s in 1895, but the value and significance of these observations seem

1 Nothnagel, Berl. klin. Wochenschr., iii, p. 31, 1866.

1 Guthrie, LaWet, i, p. 193, 1894.

* Stocker, Centralbl. f. Gyncikol., No. 45, 1895.

4 Brewer, Ann. of Surg., xxxvi, p. 481, 1902. s Brackett, Stone, and Low, Boston Med. and Surg. Journ., cli, p. 2,

1904. 6 Kelly, Anu. of Surg., xli, p. 61, 1905. * Bevan and Favill, Jowrn. of Am. A4ed. Assoc., xlv, pp. 691 and 754,

1905. * Greven, Uebsr Acetonurie nach der Narkose. Bonn, 1895.

239

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240 Acetonuria Following Chloroform and Ether

to have escaped any widespread notice. Greven studied 251

cases of anzesthesia under chloroform, ether, and bromethyl, and found that acetone appeared in the urine in 167 cases. In many of these examinations he tested the urine directly without dis- tilling, which is a less accurate method than Lieben’s iodoform test applied to the distillate.

In the report of Brewer’s case of chloroform poisoning, he states that he has had routine examinations made in thirty- three cases of ansesthesia from ether and chloroform and that acetone was found in seven of these cases. Since then Dr. Brewer has had further examinations made, the summary of which he has allowed me to report with the present series of cases. He had an examination for acetonuria made in the case of seventy- eight patients in addition to the thirty-three mentioned above. In sixty-four cases, where the examination was made on the day following operations, the acetone reaction was well marked in fifty-nine. In ten cases not examined till the second day after the operation, there were seven positive results. In two cases not examined till the third day after the operation, there were two negative results.

In several cases where acetone was found immediately after operation, it persisted a number of days: in one case for seven days and in two cases for ten days.

In twelve cases of postoperative acetonuria, tests were made for diacetic acid with one positive result.

Dr. Brewer concludes from his cases that in at least ninety per cent. of cases there is a well marked acetonuria during the first few hours after anasthesia.

As it has been generally considered that, barring some idio- syncrasy or the presence of some organic disease, the giving of chloroform and ether does not produce any really unfavorable effect upon the patient, it has seemed well to make further routine examinations regarding the changes occurring in the urine after the use of amesthetics. The following report relates to the analysis of the urine in forty-one cases of anssthesia occurring in the service of Dr. Brewer at the Roosevelt Hospital. These patients were anasthetized with chloroform or ether or with a combination of the two. The results of the analyses are given in the accompanying tables.

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244 Acetonuria Following Chloroform and Ether

TABLE II.

(CASES 27-34 OF TABLE I.)

L9667 ..2633

L .690 L767t

1.264E 1.210s

1.911f b.7441

1.0841 1.428f

B

-

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i .

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- m

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1 .

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! I .

i .

-

Operation.

Hernia tefore (Bassini) Lfter El* 1.77 1111

3.60 3046

Cleft Palate Adenoids

13. 12. ::4882

7.19 6356 3.21 0167

10.4 20.4

;::

2

Il.s 21.8

14.4 17.6

-- 20.9 20.3

4.764 2.22 0972 13.06 ,024 4831 :::

-- i-m acted

P Et%% -- --

-- Inguinal

Adenitis --

‘E

Intermuscular Appendicectomy

Cholelithiasis 6.87 7.88 0.85 6.07

r3.9 .1.16 8112 ;:28

7.61 4742 -- -.

Ventral Hernia 6.3 E3

Thyroid Cyst

In studying these tables it will be noted that in all but two of these cases, acetone 1 was excreted in the urine during the first twenty-four hours after the operation. In eight of these cases only a trace of acetone was found, and in the remaining twenty-

* The following method was used in testing for acetone: fj C.C. of strong H,SO, were added to xoo C.C. of urine which was then distilled. About 60 cc. of the distillate were collected. A portion of this was warmed in a test-tube and rendered alkaline by the addition of a few drops of a solution of potassium hydroxide. Then Lugol’s solution of

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Helen Baldwin 245

nine (or 70 per cent.) there was a marked reaction. In twenty- eight cases ether alone was used. In eight of these there was a trace of acetone after the operation, and in twenty there was a marked or very marked reaction. In nine cases chloroform alone was used. In one of these there was no acetone excreted in the urine.; in two cases there was a trace and in six there was a marked reaction. In four cases chloroform and ether were both used, and of these one had no acetone and three had a marked reaction. It would appear from these observations that a marked reaction for acetone is as likely to occur after ether as after chloroform anasthesia. The average duration of the opera- tions in which chloroform alone was used was thirty-three min- utes, that in which ether alone or ether and chloroform were used was forty-six minutes.

The duration of the ana3sthesia did not have as much effect upon the amount of acetone excreted as might have been ex- pected. The effect of the length of the operation may be seen in the following summary:

Duration of operation.

Acetone reaction.

NOll6. I Trace 1 Marked. I Very Marked.

30 min. or less..

Over one hour. .

In only two cases was the test for acetone continued after the first twenty-four hours following the operation, and in both of these there was still a marked reaction on the second day, but much less on the third. Greven found in his cases that the ace- tone usually disappeared from the urine within a few days’ after the operation.

The urine of each patient was tested for acetone before the operation. In six cases acetone was present. In the rest there was none found or only a trace which was not more than a

iodine was added drop by drop until there was a slight excess. The solution of potassium hydroxide was again added, drop by drop, until the brown color disappeared. With this test, if acetone is present, there is a prompt precipitation of iodoform.

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246 Acetonuria Following Chloroform and Ether

physiological amount. The conditions in which acetone was found before operation were appendicitis (two cases), thyroid tumor, adenitis, hydrocele, and abscess of the kidney. In three of these acetone was definitely increased after the operation. In two, appendicitis and enlarged thyroid, the acetone was less after the operation than before.

As it has been claimed that the giving of carbohydrate food greatly lessens the amount of acetone in the urine, in pathologi- cal conditions, or causes its disappearance, rather large quanti- ties of sugar were given to six of these patients before the operation to discover whether it would prevent the appearance of acetone after the narcosis, Two patients received 25 grams of cane-sugar, three received ~5 grams, and one, 150 grams. The giving of the sugar did not appear to affect the amount of acetone excreted. In all these cases receiving sugar, there was a distinct reaction for acetone after the amesthesia; in three cases the reaction was marked, and in one very marked.

An examination for diacetic acid r was made in fifteen cases in the urine excreted during the first day after the operation, and in all of these the result was negative. In two cases, how- ever, a test was made for diacetic acid in the urine collected on the second and third day after the operation, and in both cases it was found in these later specimens.

The presence in the urine of these patients of certain other organic acids, including aromatic oxy-acids and hippuric acid (see table), was tested by adding sulphuric acid and extracting the urine with ether. After washing this extract to remove all traces of sulphuric acid, the residue was titrated with decinormal sodium hydroxide solution to determine the acidity. Fourteen of the specimens collected before and after the operation were thus examined. The average excretion of organic acid thus determined was, in the specimens before the anaesthesia, equiva- lent to 25.4 C.C. of a decinormal solution of sodium hydroxide. The average of the specimens collected after the amesthesia was equivalent to 13.5 C.C. of the same solution.

1In testing for diacetic acid a solution of ferric chloride was added in a slight excess. If the Bordeaux-red color appeared, another portion of the urine was boiled, after the addition of a few drops of sulphuric acid, and again tested with ferric chloride.

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Helen Baldwin 247

In six cases the nitrogen of ammonia i in the urine was esti- mated before and after the operation, The average nitrogen of ammonia excreted in the specimens collected before the opera- tion was 7.1 per cent. of the total nitrogen, and in the specimens after anesthesia 6.2 per cent. of the total nitrogen. The varia- tions in the different cases are such that no definite conclusions can be drawn from so few cases, That there is no tendency in the first twenty-four hours for the nitrogen of ammonia to in- crease is noteworthy, as it corresponds to the evidence that there is no increase in organic acids.

A number of the specimens of urine were tested for indications of the degree of bacterial activity in the bowel before and after the operation, It seemed especially desirable to do this, for the reason that a paralytic condition of the intestines has often been suspected or observed after narcosis, and it would be reasonable to suppose that this disturbance of function and the diminished secretion of ‘digestive juices which is supposed to occur might lead to an increased production and absorption of putrefactive products. There has been a disposition to attribute to intes- tinal putrefactive products symptoms which are now being re- ferred with a high degree of probability to the influence of the amesthetics upon the cells of parenchymatous organs. In thirty-five cases a test was made for phenol.2 Of these, twenty excreted less phenol after the anesthetic than before, five had the same amount before and after the operation, and ten showed’ more,after the anzesthesia. In only eight cases was a test made for indican,a and in six of these there was no indican in the urine either before or after the operation. Two that had a marked reaction before showed less after the operation.

In eight cases an examination was made to determine the ratio of the preformed to the ethereal sulphates,* before and

1 The nitrogen of ammonia was estimated by Schlosing’s method. 8 The distillate from the acidified urine was tested with Millon’s re-

agent for phenol. 8 To test for indican, equal parts of urine and a solution of ferric

chloride in fuming hydrochloric acid were mixed. The mixture was then agitated with a few drops of chloroform which takes up the blue pigment.

4 The preformed and ethereal sulphates were estimated by Salkowski’s gravimetric method.

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248 Acetonuria Following Chloroform and Ether

after the operation. This ratio was eleven to one before, and fourteen to one after, the operation. Neither these ratios nor the totals point to an increase in ethereal sulphates immediately after narcosis.

Although we thus note that in these cases there was no in- crease in the intestinal putrefaction following the narcosis, the study of the putrefactive products in persons subjected to an- zsthesia may nevertheless prove to be a matter of very great importance in connection with increased susceptibility to the toxic action of narcotics. For it is conceivable that chronic states of putrefaction, which have led in the course of time to impaired liver function, may have a real part in explaining the susceptibility of exceptional patients to chloroform and ether.

The characteristics of the urine after amesthesia, as shown in this limited number of cases, are a higher specific gravity, a more strongly acid reaction, and an excretion of acetone, which in seventy per cent. of the cases gave a marked reac- tion. The organic acid was usually less than before the opera- tion and the excretion of ammonia less, while the products of intestinal putrefaction were not materially altered, being slightly diminished.

The point of especial interest in this series of observations is the confirmation of Greven’s discovery, that the routine exam- ination of the urine following anaesthesia shows that in almost every case there is enough disturbance in metabolism, probably in the liver cells, to cause the appearance of a distinct or marked reaction for acetone in the urine. It is also noteworthy that in this limited number of observations this mild degree of meta- bolic disturbance is as likely to follow ether as chloroform an- resthesia, and does not bear any definite relation to the amount of the amesthetic used, but may give a marked reaction after a short operation where a small amount of the ether or chloro- form is given.

The observations recorded here relate to cases in which narcosis was followed by no untoward results referable to the amesthetic, and may therefore be regarded as typical of normal amesthesia by chloroform and by ether.

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Helen Baldwin 249

I wish to acknowledge my obligation to Dr. Herter at whose suggestion this study was made, to Dr. Brewer for kindly placing his patients under observation, and to Drs. Coerr and Hervey for making careful records of the clinical features in these cases,

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Helen BaldwinANÆSTHESIA

CHLOROFORM AND ETHER ACETONURIA FOLLOWING

1906, 1:239-249.J. Biol. Chem. 

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