Trilene, an adjunct to obstetrical anesthesia and analgesia

TRILENE,*

AN ADJUNCT AND

TO OBSTETRICAL ANALGESIA+

ANESTHESIA

CHARLES E. FLOWERS, JR., M.13., BROOKLYN, (Prom

the Bate

University

Department

of New Podc at New of Obstetrics ami

York City, Gynecology)

N. Y.

College

of Xedicine,

INCE Simpson administered the first obstetrical anesthetic in 1847 and von Steinbuchel gave the first obstetrical analgesic in 1902, obstetricians as well as their patients have fervently hoped for the panacea for obstetrical pain. It has not been found. But from the varied opinions which exist concerning obstetrical pain relief and the voluminous literature on the subject, it is quite evident that the majority of obstetricians have selected certain analgesic and anesthetic techniques that are at least individually satisfactory. Some physicians hope to achieve complete analgesia, amnesia, and anesthesia. Others advocate natural childbirth and believe that parturition and labo-r should be physiological and practically painless. Ii-Iowever, between these two extremes lie the majority of the American obstetricians who use various tech:niques of conduction anesthesia and who employ various dosage schedules of hypnotics, amnesics, and analgesics. However, each new drug and analgesic technique that is introduced is met witb curiosity and a hope that it will prove useful. It is thus that Trilene has been received in the United States. Hewe? introduced trichlorethylene as both an analgesic and anesthetic agent. However, it is felt that in obstetrics the pharmacological action of the drug dictates its use purely as a potent analgesic, either alone or as an adjunct to other obstetrical anesthetic techniques.

S

Chemical

Composition

aad Pharmacologicad

Action

The clinical application of any drug is dependent upon its pharmacological Trilene has the following chemica,l formula ClCI-I = Ccl,. The color and smell of Trilene closely resemble those of chloroform. The boiling point is 86O C., making the vaporization of the drug insufficient for use on an open mask. It cannot be employed with soda lime, since toxic dichl.oracethylene is formed. Table I2 compares Trilene with chloroform, ethylene, and ether. It is apparent that Trilene is related to both chloroform and ethylene and shares some of the favorable characteristics of ethylene and a few of the unfavorable qualities of chloroform. If one defines the margin of safety as a difference between the percentage of a, given drug which will c,auseanalgesia, and the percentage of the drug which will be fatal, it is evident that Trilene with at least a 3 per cent margin of safety is superior to chloroform which has a margin of 0.65 per cent but somewhat inferior to ether which has a safety margin greater than 8 per cent. Trilene’s --

action.

*Purified trichlorethylene, Ayerst, McKenna and Harrison Limited, New York City. TPresented at a meeting of the Brooklyn Gynecological Society, Nov. 19, 1952.

FLOWERS

effect upon the respiratory and vasomotor centers is similar to that of ethylene and ether. Neither center is adversely affected whereas in chloroform both are depressed. Trilene depresses the vomiting center; thus the danger of aspiration of vomitus is negligible even in the unprepared obstetrical patient. This factor is of fundamental importance since one of the greatest dangers in obstetrical anesthesia is aspiration of vomitus3, 4 The harmful effects of chloroform upon the liver have almost become legend.5 Since t,he chemical formula of Trilene is closely related to that of chloroform, liver necrosis from Trilene was viewed as a possibility. However, Waters6 and his colleagues have recently emphasized that in the presence of administered anesthesia, adequate glycogen, oxygen,. protein, and skillfully chloroform produces neghgible hepatic injury, possibly only slightly greater than ether. Armstrong? in his excellent monograph on “The Assessment of Liver Damage Following Trichlorethylene Anesthesia’ ’ asserts that the transient liver damage caused by triehlorethylene is less than that due to ether. Herzbergs has similarly shown that there is essentially no liver damage resulting from Trilene. However, if one wishes to maintain the maximum margin of safety it must be realized that ether and Trilene are both capable of producing slight glycogenolysis and only the well-hydrated patient should receive prolonged Trilene analgesia. TABIJ;

I.

PHARMAC~LUGICAI~

OF TRILENE*

COMPARISON

TRILENE dCH=CCl,

analgesia

0.5%

Anesthesia Respiratory arrest Respiratory center Vomiting center

1.2% 3.5%

ETHYLENE H,C!=CH?

CHLOROFORM CHCI,

25%

1.35%

ETHER H&-O--C&

Too

irritating

for

1.65% 2.00%

use

Stimulated

85% Does not occur without anoxia Sot affected

Depressed

Stimulated

Depressed

Not.

affected

Depressed

Vasomotor cente.r Liver function

Not

Not

affected

Depressed

Btin@ated in light anesthesia Not affected

Function depressed less than with ether and chloroform

Not

affected

Function pressed

Heart

Unchanged in analgesia; fatal arrhythmias possible in deep anesthesia Minute volume increased

Cardiac output and rhythm unchanged

Cardiac: output. decreased 30% : ventricu lar fibrillation possihle

Minute volume unchange,d Yes

Minute

LUIl@

Fxplosion . _ hazard

Above

affected

NO

Above

de

volume

decreased NO

4% 8%

%nction depresse.d for 24 hours less than with chloroform-more than with Trilene Cardiac output increased ; minor Grade I arrhyt,hmias

mnute volume increased Yes

The effect of Trilene upon the cardiovascular system warrants serious eonsideration. All of the known anesthetic gases, et,her, nitrous oxide, eyclopropane, chloroform, and Trilene may produce cardiac arrhythmias. These a,rrhythmias may be divided into two groups. Group I is due to increased vagal tone and is manifested by nodal rhythm, delayed auricular vent,ricuIar condue-

Volume Number

65 5

TRILENE

FOR

OBSTl!XRICAL

ASESTHESIA

AND

ASALGEHIA

1029

tion, and bradyeardia. They are generally not manifested clinically and they are considered harmless. Group II arrhythmias are dangerous and are manifested by multifocal ventricular tachycardia, cardiac standstill, and ventricular fibrillation. These may occur in moderately deep cyclopropane and light ethyl chloride and chloroform anesthesia. However, Group II arrhythmias occur only in the lower first and second plane of Trilene anesthesia.g Therefore, Trilene is recommended only for analgesia in obstetrics and with such use the danger of primary cardiac failure is negligible. Hingson has stated in reference to the previously reported* obstetrical deaths under Trilene, “None of these deaths were associated with Trilene as an analgesic, and were possibly caused by the use of impure trichlorethylene in the early development of the drug. “lo The pulmonary complications with Trilene analgesia are not important. The minute volume of inspired air is increased and tachypnea seldom occurs except when anesthetic concentrations of the drug are employed. Kidney function is unimpaired. Metho8d of Administration In the hands of a well-trained anesthesiologist, Trilene may possibly be But the place of Trilene in obstetrics is only for used for surgical anesthesia. analgesia. It may be empIoyed either alone or as an adjunct to other techniques of obstetrical pain relief. When Trilene is used purely for analgesia the pharyngeal reflexes are not abolished a.nd aspiration of vomitus does not occur. Serious In the presence of adequate glycogen, liver cardiac arrhythmias are avoided. damage is unimportant. The index of safety is extremely high. Of great practical important is the fact that the agent may be self-administered with safety.

Fig.

1.

The success of Trilene administration depends directly upon the cooperation of the patient and the care that the obstetrician takes in instructing the patient in the use of the agent. The most practical and economical device for administering Trilene is the “Duke inha.ler” designed by C. R. Stephenl’ (Fig. 1).

Fig. 2 represents the vapor concentrations at the various scale settings for the ’ ‘ Duke inhaler. ’ ’ It is evident that the maximum safety and usefulness Thus, the scale sett,ings on the inof the drug in obstetrics are for analgesia. haler should be at analgesic concentrations; this will vary bet,ween three and six inclusive. The vapor concentrations should be low until the patient is aceustomed to the smell of Trilene; then the concentration should be raised until the desired depth of analgesia is achieved. The first two or three breaths of Trilene should be taken with the mouth open and the mask only loosely applied to the face. When Trilene is used in this manner there will usually be little objeetion to its smell. The wrist strap should always be used during self-administration so that the inhaler may be allowed to fall from the patient’s face when anesthesia apWhen Trilene is administered to a patient with the inhaler the mask proaches. W%en these should always he removed when the patient loses consciousness. two safety factors are used, the patient will receive only analgesic concentrations of Trilene. at

Fig.

Clinical

a.

Application

Since Trilene is recommended only for obstetrical analgesia it should !toi be used when profound anesthesia is needed for a difficult delivery. In such cases spinal anesthesia is perhaps the technique of choice. When uterine relaxation is necessary cyclopropane-ether are the agents of choice. The final use of Trilene wil1 depend upon the philosophy of the individual obstetrician. For the obstetrical specialist who desires to have the patient unconscious under profound analgesia, Trilene wilI be useful only before the uterine contraction pattern has developed sufficiently to employ large doses of analgesic or hypnotic drugs. For the general practitioner or the obstetrical specialist who advocates natural childbirth or minimal analgesia, Trilene is useful either alone or in combination with small doses of Demerol, Seconal, or Xembuta.1. When pudendal block, spinal, caudal, or local anesthesia for cesarean seetion is not completely satisfactory, Trilene may be used as an adjunct.

zhmrr”s’

TRILENE

FOR

OBSTETRICAL

ANESTHESIA

$ND

ANALGESIA

1031

For the average obstetrical specialist Trilene will find its greatest value as a general handy agent on the delivery floor. It is ideal for a precipitate delivery; it may be used successfully while the nurse is preparing analgesic drugs or the obstetrician is awa.iting the arrival of the anesthesiologist. It is the safest analgesic agent for t,he infant when the patient arrives late in labor, and it is the safest agent available for the easy multiparous delivery. It has been particularly valuable in t.he Kings County Hospital where the acute shortage of nurses and anesthetists previously made it impossible for all patients to receive analgesia and relief of pain at delivery. Table II illustrates the use of Trilene in 602 patients. In 315 of these patients, Trilene was used either alone for analgesia in spontaneous delivery or in combination with small doses of Demerol ancl Nembutal. The five breech deliveries were for immature or premature infants presenting by the breech. Trilene was empIoyed in combination with pudendal block with or without Demerol or Nembutal in 258 deliveries. There were 56 low forceps, 7 midforceps, and 5 operative breech extractions. TABLE

II.

I ) NUMBER

Triiene Trilene Trilene Trilene Trilene section ‘rota1

audendal block ‘spinal caudal local, cesarean

CLINICAL

ITANEOUS IDELIVERY)

APPLICATIONS

1 FORCEPS

OF TRILEXE

I / BREECH

315 ?a 15 10 4

310 190 0 0 -

0 63 1.7 10 -

5 5

602

500

88

I 1

FULL TERM

I PREIMATURE]

1

IMMATURE

20 11

-

290 247 15 10 4

0

5 0 0 0 0

10

566

31

5

When Trilene was used as an adjunct to other t.ypes of analgesia for precipitate deliveries and for analgesia late in labor it was accepted by the patient with enthusiasm and almost universal satisfaction. -When it was used alone or in combination with other analgesic drugs it was satisfactory in about 80 per cent of the cases. Ten per cent of the patients found the odor of Trilene objectionable and refused the inhaler. The majority of these patients were either uncooperative or presented a language barrier. Table III shows that the incidence of postpartum hemorrhage and manual removal of the placenta was no greater than would be expected in uncomplicated vaginal deliveries. The incidence was less than the clinic average of 4 per cent. There were 12 fetal deaths; 7 of the infants had no fetal heartbeat at the time of administration of Trilene. There were 4 death-s of immature infants and one death in a premature associated with several congenital anomalies. The corrected fetal loss of all infa,nts who weighed above 1,000 grams was 0.

The Effect of Trilene

Upon the Infant

There is no agent which will produce sedation or analgesia in the mother that does not traverse the placenta and become a potential cause of asphyxia neonat0run~.12~ I3 The effect upon t.he infan.t will depend upon the concentration of the drug administered and the rapidity with which it is metabolized or eliminated. Trilene is no exception. But when it is administered as an analgesic agent to the mother, it will have only an analglesic effect upon the infant. Trilene is eliminated from the blood stream with the same rapidity as chloroform.14 Thus, any depressant effect upon the infant will be transitory. There were 6 infants in this series of 602 cases requiring positive pressure This is an incidence of 1 per cent which is the same figure reresuscitation. ported by Gordon and Mortonlj in 669 obstetrical patients.

~-.

~..

Trilene Trilene Trilene Trilene Trilene sectlon Total

.---.

---

602 --___

1 CASES 315 258 15 10 4

-----

-- - -----~

alone pudemlal block spinal caudal local, cesarean

-... .-.-._----

1

I

0

i 0

LOSS 0 0

III.

i .--5

TABLE

- --.._

1V.

1

1 PLACENTA 3 2 0

I

I

6

4 2 0 0 0

RHAGE

6

ii

3 3 0

TION

OF TRILENE

1

I

COMPLICATIONS

EFFECT

OBSTETRICALDIFFICULTIES

TABLE

UPON

TRILENE

TIIE

INFANT

1

:,

::

4

0

CONGENITAL MALFORMATION

4

IMMATURES

_l__---._-

WITH

7

2

12~.--.-~

3"

IJNCORREGTED FETALLOSS

_________-~-___I --

PERINATALLOSS STILLBORN, FETALHEART TONESABSENT BEFORE ADM. 5

0

0

--.

~~~ _^

CORRECTED FETALLOSS ABOVE l,oooGRAMS

-

Volume tij Iumber

TRILENE

FOR

OBSTETRICAL

14NERTHEHIA

5

AND

,4NALGESIA

1033

‘Table IV represents a critical analysis of the effect of Trilene upon the infant. Breathing times and crying times were accurately obtained at 100 de1iver:ies. The number of infants with breathing time in excess of 1 minute and crying time in excess of 2 minutes, and the number of infants requiring positive pressure resuscitation were essentially the same as in 140 randomly selected deliveries where no anesthesia or analgesia was administered. If ‘This does not mean that Trilene will cause no depression to the infant. Trilene is administered too long or in too great a concentration, it is possible to It does signify, however, that the intelligent intercause asphyxia neonatorum. mittent use of Trilene as an analgesic is not generally fraught with danger of fetal depression.

Summary Trilene is a potent analgesic drug. Its margin of safety and ease of administration will ultimately make it a standard agent on all delivery floors. Trilene’s wide variety of uses will probably allow almost every obstetrician to find a place for it in his obstetrical practice.

References Proc. Roy. Xoc. Med. 35: 463, 1942. C. L.: John : The Pharmacology of Anesthetic Drugs, Springfield, Ill., 1.950, Charles C Thomas. Merrill, R. B., and Hingson, R. A.: Anesth. & Analg. 30: 121, 1951. Hingson, R. A., and Hellman, L. M.: Anesthesiology 12: 745, 1951. Bull. Joham Hopkins Hosp. 20: 278, 1929. Whipple, G. H., and Speery, G. A.: Waters, R. M.: Chloroform, a Study After 100 Years, Madison, Wis., 1952, The University of Wisconsin Press, p. 21. Armstrong, D. N.: The Assessment of Liver Damage Following Trichlorethylene Anesthesia, Colombo, Ceylon, 1945, Mortlake Press. Anesth. & bnalg. 13: 203, 1934. Herzberg, M.: Proc. Roy. Sot. Med. 37: 526, 1944. Barnes, B. G., and Ives, J.: Hingson, R. A.: Personal communication. Stephen, C. R., Nowill, W. K., and Martin, R.: Anesthesiology, Nov. 1952. A Pharmacological Approach to Obstetrical Anesthesia and Analgesia. Flowers, C. E.: In press. Anesthesia 4: 14, 1949. Helliwell, T. J., and Hutton, A. M.: Brit. J. Indust. Ned. 2: 142, 1945. P’owell, J. F.: Anesthesiology 12: GSO, 1951. Gordon, R. A., and Morton, M. D.:

1. Hewer, 2. Sdriani, 3. 4. 5. 6. 7. s. 9. IO. 11. 12. 13. 14. 15.

UNIVERSITY

HOSPITAL,

CHAPEL

HILL,

N.

C.