THE ACTIONS AND USES OF PENTAL. BY DAVID CERNA, M:D., Ph. D., Demonstrator of Physiology in the Medical Department of the University of Texas ; formerly Demonstrator of and Lecturer on Experimental Therapeutics in the University of Pennsylvania, etc., etc. REPRINT FROM American Medico-Surgical Bulletin, October, 1893. TO CONTRIBUTORS. 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D., Demonstrator of Physiology in the Medical Department of the University of Texas ; formerly Demonstrator of and Lecturer on Experimental Therapeutics in the University of Pennsylvania, etc., etc. REPRINT FROM American Medico-Surgical Bulletin, October, 1893. ERRATUM. The diagrams, Fig. 2 and Fig. 3, were transposed by the printer's error. Properly the plot marked ''Fig. 3, Plot of Experiment. VI," should be "Fig. 2, Plot of Experiment V, " and vice versa. THE ACTIONS AND USES OF PENTAL. * By DAVID CERNA, M.D.. Fh. D., Demonstrator of Physiology in the Medical Department of the University of Texas ; formerly Demonstrator of and Lec- turer on Experimental Therapeutics in the University of Pennsylvania, etc., elc" PENTAL is a product obtained from amylene hydrate when this latter substance is heated with acids. The new anaesthetic is also termed Trimelhylethylene and Beta-iso-amylene, the chemical composition of which is repre- sented by the formula, (CH,)4:C:CH (CH,) ; or CgH10. Pental is a colorless, highly inflammable liquid, burning with an illuminating flame. It has a specific gravity of 0.678, and a boil- ing point of 100 40 F (38° C). Although ex- ceedingly volatile, it does not decompose on exposure to light or to the atmosphere. Pental is soluble in alcohol, ether, and chloroform, but is insoluble in water. The interest which the new drug has awakened as a general anaesthetic in surgi- cal practice, necessitates that its physiologi- cal action be studied carefully. More or less extended researches in the clinical wards have been made, especially in Eu- ♦ Read before the Texas State Medical Association, at Gal- veston, May, 1893 rope, regarding the effects of pental in the animal economy ; but no elaborate studies as to how such effects are brought-about have been made. The alleged chief action of the agent as an anaesthetic, leads to the importance of a knowledge of the behavior of the new drug, particularly on the circulation and the res- piration. To these two symptmraG I have con- fined for the present my experimental studies. In a paper entitled "Chloride of Ethyl and Pental," published by Prof. H. C. Wood and the writer (*), a note is appended in re- gard to the actions of pental ; but this latter study, only preliminary and superficial, can- not be considered by any means as conclu- sive. From the details, however, of one of the experiments performed, it was observed that the production of anaesthesia with pen- tal in dogs was each time accompanied with a marked fall of the arterial pressure. The rate of the respiration was increased, al- though the extent of the respiratory move- ments, most of the time, was not distinctly above the normal. The accompanying tracing in the paper referred-to, shows the depressing effect of pental upon the heart ; this organ being affected much more se- verely than the respiratory centers, since the respiratory movements continued after the cardiac viscus had ceased to beat. * Dental Cosmos, }\x\y, 1892; also, Transactions of the Phila- delphia County Medical Society, 1892. 4 Wood and the writer concluded, then, from such evidence, that pental would prob- ably prove to be a dangerous anaesthetic ; and that, if extensively used, it would pro- duce death by cardiac paralysis; and further, that, even in non-fatal cases, the after-effects, in the human being, would be disagreeable from the fact that in the dog a peculiar wild excitement was noticed di- rectly after the anaesthesia from the drug had gone off. In continuing my own studies with pen- tal, I have instituted a special series of ex- periments, begun at the laboratories of the University of Pennsylvania, and finished at the physiological laboratory of the Uni- versity of Texas, at Galveston. My experi- mentation may not be an elaborate one, per- haps, but it is sufficient, I believe, to show the range of action of the drug in question upon the circulation and the respiration. I divided my experiments into three series, as follows : i, those performed upon normal animals ; 2, those made in animals whose vagi had been previously cut; and 3, those performed upon animals in which the spinal cord and vagi had been previously severed. The animals used were exclusively dogs. The dog was first etherized in order to perform the various operations for the prep- aration of the animal. After the connection with the recording kymograph was made,- of the respiratory apparatus by means of a 5 tracheal tube and the corresponding Marey's tambour, and of the circulatory apparatus by the usual methods,-the animal was al- lowed to recover completely from the effects of the ether, in order to avoid, as far as pos- sible, vitiated results. The pental was administered by inhala- tion or intravenously. As objection might be taken to this latter method of adminis- tration, I may here repeat what Wood and the writer (*) have already remarked : that "it is plain that whether a drug be injected directly into the jugular vein, or whether it enter the system by absorption into the pul- monary capillaries, it must first reach the heart before being diffused throughout the general circulation. In the one case the drug passes first into the right side of the heart, while in the other case it goes into the left side of the heart." Various experiments, in tabular form, and also by means of plots, are presented here- with. The most superficial analysis of these experiments will reveal the fact that pental is capable of producing anaesthetic effects, but that these effects are generally accompanied with disturbances of respira- tion and, particularly, of the circulatory system. Thus, in Experiment I, the first inhalation of ten grammes of the drug was followed by ♦ Loc. citaf. 6 Experiment No. I. TIME. M. S. Cd cn O Q PRESSURE. MM. PULSE. PER MIN. RESP. PER MIN. REMARKS. NORMAL. Pental by inhalation. O. 160 134 24 8.00 162 I32 24 Inhalation begun, of one bottle (10 grammes), poured into an ordi- nary inhaler. 8.30 140 102 38 8.40 138 102 46 9.00 130 92 5° Palpebral reflexes weak ; inhala- tion ended. 9.20 150 96 58 9-40 158 98 52 Reflexes normal again; animal much excited; salivates and urinates. H-3° 164 136 60 Inhalation of second bottle begun. u-5° 128 98 Respiration irregular and shal- low. 12.00 * 98 68 102 Anaesthesia apparently complete; but conjunctival reflexes not en- tirely lost. 12.50 98 IS2 102 Pulse small; respiration exceed- 5 ingly shallow; removed in- haler. 13.10 3 142 146 96 13-40 150 134 82 14.20 158 132 52 Reflexes normal again ; dog very restless and whines. 17.30 162 i36 40 Dog continues very restless. 18.40 162 134 40 Inhalation of third bottle begun. 19.50 60 76 78 Inhalation ended ; respiration shallow, with a tendency to the Cheyne-Stokes type; reflexes weak, but animal apparently narcotized. 20.20 132 142 62 20.50 166 168 S2 21.30 162 162 42 Animal has regained conscious- ness, whines, and is very much excited. 24.00 160 168 48 Dog continues excited ; pants as if much fatigued. Was after- ward killed. Dog-weight, 11.5 Kilos. a decline of both the blood-pressure and the 7 Experiment No. II. Dog-weight, 12 Kilos. TIME. M. S. DOSE. GME. PRESSURE. MM. PULSE PER MIN. RESP. PER MIN. REMARKS. NORMAL. O. 170 I48 18 Pental intravenously. 10.00 0.2 176 152 18 Injection begun. XO.2O 158 I36 24 Injection ended IO.4O 11 .OO 12.50 I46 148 152 120 120 I42 36 38 32 Pulse irregular; palpebral re- flexes weak ; pupils dilated. 1330 l68 148 36 Apparently conscious again, but restless. 14.00 °-3 168 I48 36 Injection begun. 14.20 I4.40 13° 120 116 98 42 56 Injection ended. IS.OO 102 128 6t> Narcotized, but eye reflexes not entirely gone ; pupils widely dilated : respiration shallow. 15 30 0-5 I IO 136 68 Injection begun. l6.OO 92 166 70 Injection ended. 16.30 80 178 76 Continues narcotized : pulse small. 18.30 I .OO 96 180 68 Injection begun. I9.OO 62 172 68 Injection ended. 19.20 40 186 52 Anaesthesia complete, but eye reflexes can still be elicited mechanically. 25.OO 158 196 60 Consciousness has returned ; animal very much excited, whining; pupils continue di- lated. 28.00 2.00 162 186 62 Injection begun. 28.30 29.OO 29 -30 56 32 28 164 146 126 64 60 48 Injection ended. 30.00 3° 3° 31.00 3i-30 l6 96 36 6 4 2 Pulse very weak. Spasm. Heart ceased. Two minutes afterward the needle registered two or three respiratory movements. 8 pulse-rate, even before the production of anaesthesia. The pressure from its normal height, 162 mm., fell to 140 mm. in the course of half a minute after the beginning of the inhalation, and to 130 mm. in half a minute longer, when the eye-reflexes be- came weak and the animal was apparently narcotized. The pulse was also reduced in rate, while the respirations were increased in number, though no change was observed in the depth of the movements. Forty sec- onds after the removal of the inhaler the conjunctival reflexes became normal, and the animal exhibited a condition of great ex- citement, accompanied with marked saliva- tion and apparently involuntary urination. The second inhalation was followed by similar phenomena as regards blood-pres- sure, pulse, and respiration. At a time, how- ever, when the anaesthesia was complete, although the pressure remained at the height of 98 mm., there was a sudden rise in the number of pulsations even above the nor- mal, although the character of the pulse in- dicated weakness. In the course of nearly two minutes after the occurrence of this phenomenon, but pulse and pressure re- turned to their normal standard, pari passu with the disappearance of the anaesthesia ; yet, the respiration continued above the nor- mal, and the animal gave evidence of marked excitement. After an interval of about five minutes, the 9 third inhalation was administered. The same results were produced : reduced arte- Experiment No. III. Dog-weight, 18.5 Kilos. TIME. M. S. DOSE. GME. PRESSURE. MM. PULSE PER MIN. RESP. PER. MIN. REMARKS. NORMAL. O. 172 l82 21 Pental injected intravenously. One vagus prepared. 10.00 170 182 21 Tested irritability of vagus with 15.00 0 5 I76 178 24 a medium current of electric- ity. Applied to central end. heart-beat ceased in 15 sec- onds ; to peripheral end heart- beat arrested in 8 seconds. Injection begun. K.2O <5-40 l6o 142 156 1.38 36 48 Injection ended. l6 OO 16.20 11 >8 98 128 112 58 68 The same electrical current ap- 22.00 22.20 0-5 168 168 162 162 38 38 plied to either end of vagus, is followed by an almost instan- taneous arrest of the heart. Injection begun. 22.40 23.OO 146 126 148 126 68 78 Injection ended. 23 3° 92 I08 82 Dog narcotized ; pupils widely 24.OO 82 102 78 dilated. Same effect as before, on appli- 24 30 °5 106 I 12 64 cation of electrical current to cut ends of vagus. Injection begun. 25.OO 92 126 60 Injection ended. 26 OO 27.OO 27.3O 42 40 36 204 214 224 62 62 68 Complete anaesthesia; same electrical cun-ent applied to vagus had now no effect on cardiac action. Animal died eventually. rial pressure and pulse-rate, and an increase 10 of the respiratory movements. And now the breathing, essentially shallow, showed a tendency to the Cheyne-Stokes type, at the very time, indeed, when the dog ap- Experiment No. IV. Dog-weight, i 2.8 Kilos. TIME. M. S. DOSE. GME. PRESSURE. MM. PULSE PER MIN. tn 2 Sg REMARKS. NORMAL. Pental intravenously: ischiatic nerve prepared. o. I42 168 26 15.00 144 166 24 16.00 o-5 14 + 166 24 Injection begun. 16.30 126 148 38 Injection ended. 17.00 118 I 20 42 Pulse-waves large. 17.40 116 126 48 19.30 °-5 120 IS6 48 Injection begun. 20.00 102 116 52 Injection ended. 2O.3O 98 112 52 21.00 98 110 58 Pulse-waves large ; animal nar- cotized ; faradization of ischi- atic nerve for 15 seconds. 21.30 120 124 42 21-45 128 •30 48 22.30 0-5 I.?O 142 48 Injection begun. 23 OO I 12 120 5f' Injection ended. 23.4O 80 116 56 23 OO 1.00 I l6 120 52 Injection begun. 25-40 98 102 5« Injection ended; pulse-waves large. Spasm of tetanic nature 26.00 102 I48 50 26.40 ICO 182 48 27 40 108 I96 48 28.00 29.OO 102 198 42 Heart ceased suddenly to act; animal continued to gasp for some time afterward. peared to be completely under the influence of the anaesthetic. About three minutes af- 11 terward, however, the animal had regained consciousness, and the signs of excitement were again manifest. The pressure went back to normal, and the pulse even beyond its original rate. In the second experiment, the drug was given intravenously. The results obtained, similar in almost every respect to those of the preceding instance, are sufficiently clear when observed in the tabular form given. There was produced the same depressant action upon the heart and the rate of the cardiac beat, and the same stimulating ac- tion on the respiration. As will be noticed, the fall in the number of pulsations was later followed by a decided increase of the same above the normal. The last injection of two grammes proved fatal to the animal, death taking place through cardiac paralysis. The explanation of the results obtained in Experiment III (these being practically the same as those of the other experiments) will be given later ; that is, when I shall enter into the discussion of how the circulatory phenomena are brought-about. I may here state that many other normal experi- ments gave almost invariably the same results. It is seen, then, from the foregoing experi- ments that pental is capable of producing anaesthesia ; but that this is, although rap- idly established, rather too fugacious for practical purposes, and that it is usually ac- 12 companied by a depressing effect upon the circulation ; that the action on the respira- tion, though apparently stimulating, is un- important. and that sometimes the latter function is dangerously interfered-with also ; lastly, that the after-effects are those of ex- citement. which, in all probability, are of a disagreeable nature. Experiment No. V. Dog-weight, 10.5 Kilos. TIME. M. S. DOSE. GME. PRESSURE. MM. PULSE PER MIN. RESP. PER MIN. REMARKS. VAGI CUT. Tube in trachea ; pental intra- venously. O. l8o 210 8 10.00 180 212 8 IO.3O 0 5 180 212 6 Injection begun. 1 I .OO 168 182 8 Injection ended. 12.00 162 176 16 *3 30 °-S 164 174 22 Injection begun. 14.00 156 166 38 Injection ended. 15.00 160 150 42 Animal narcotized. 16.30 162 158 48 17.00 o-5 162 158 46 Injection begun. *7'3° 142 140 56 Injection ended. 18.00 1.00 128 132 50 Injection begun. 18.30 106 120 32 Injection ended. 19.30 82 80 IO 21 ,OO 40 32 10 22.30 22 18 8 23.OO 4 Heart stopped. 24.OO 26.00 2 Animal dead. These general results appear to sustain those previously obtained by Wood and myself. Again, my own experience with 13 the drug agrees more or less with that of Calab (*) and that of Weber (f). Calab, as a result of considerable clinical experience and of a series of experiments on dogs, has concluded that anaesthesia as produced by pental is superficial; that the time necessary to obtain sufficient anaesthesia for ordinary Experiment No. VI. Dog-weight, 10.3 Kilos. TIME. M. S. DOSE. GME. PRESSURE. MM. PULSE PER MIN. RESP. PER MIN. REMARKS. Vagi and Cord severed ; cord cut in cervical region (i) Pental intravenously'. O. 68 124 I.30 0.5 68 122 Injection begun. 2.00 52 102 Injection ended. 2.30 42 98 3.00 44 98 4 3° °-5 46 98 Injection begun. 5.00 32 80 Injection ended. 5 4 28 46 6.00 22 30 7.00 18 22 Killed eventually. surgical operations is much longer than with chloroform ; that pental has a depressant effect on the circulation, and, when given in sufficient quantity to produce complete anaesthesia, may cause grave results ; and that, finally, the local anaesthesia produced by pental is inferior to that caused by ether. * Clinica ; Bucharest, January, 1F92. t Deutsche Medicin. Wochenschr.; Leipzig, Feb. 16, 1892; and Miinchener Medic. Wochenschr.; No. 2, 1892. t Post-mortem examination showed that the cord had been completely severed. 14 Fig. i.-Plot of Experiment II. (Normal.) Heavy line-Blood-pressure. Broken line-Pulse. Dotted line (with numerals to the extreme left)-Respiration* TIME IN SECONDS: 15 Fig. 2.-Plot of Experiment V. (Vagi cut.) Heavy line-Blood-pressure. Broken line-Pulse. Dotted line (with numerals to the extreme left)-Respiration TIME IN SECONDS: 16 TIME IN SECONDS Fig. 3.- Plot of Experiment VI. (Vagi and Cord cut.) Heavy line-Blood-pressure. Broken line-Pulse. Weber noticed excitement in some human beings, and in a few other instances slight tetanic spasms in the arms and legs. In the case of an alcoholic, the excitement was very marked. Let us examine into how the various phe- nomena above described are brought-about. Ancesthesia.-When pental is adminis- tered by inhalation, the anaesthesia occurs, as is shown by Experiment I, in from i minute to i minute and 20 seconds, and lasts for a period varying from 20 seconds to 1% minutes after the removal of the in- haler, although this must depend largely upon the quantity of the drug inhaled. No doubt a longer period of anaesthesia than the one I have referred-to could be in- duced by a persistent administration of the drug. The same may be said in regard to the administration of lhe agent intravenously. I found that I could keep the animal narco- tized as long as the repeated introduction of small quantities of pental was maintained. When the drug is given intravenously there is a tendency for the anaesthetic effects to occur sooner and last longer than when the drug is administered by inhalation ; prob- ably from the fact that a larger amount of the medicament is acting at once in the former instance ; and that in the latter the drug is rapidly eliminated by the lungs, ow- ing to the volatile nature of pental. Yet, 18 even when not taken directly into the circu- lation, the drug produces quick anaesthetic effects, it is true ; but these disappear also in a comparatively rapid manner. The anaesthesia caused by pental is chiefly of central origin, as shown by the fact that even when the loss of consciousness was complete, the conjunctival or palpebral re- flexes wrere not entirely destroyed, since they could be elicited by mechanical stim- uli. Undoubtedly, the local anaesthetic ac- tion of pental, if it has any, is very weak. On blood-pressure.-The blood-pressure in the normal animal is usually depressed by pental, as an examination of the preced- ing experiments reveals. A careful study of these experiments will show also that for a certain period of time the rate of the pulse varied pari passu with the changes of the pressure ; the former be- ing slowed, or increased in rapidity, accord- ing as there occurred a diminution or an in- crease in the height of the latter. So that two curves, for instance,-one representing the rate of the cardiac beat, and the other the changes of the arterial pressure -taken from a tracing of an animal under the in- fluence of pental, would undoubtedly show a more or less parallel course. This, in it- self, is a very significant fact, and appears to point to an action of the drug exercised on the heart itself or upon the innervation EFFECTS ON THE CIRCULATION. 19 of the organ. An opposite course of the curves would indicate a vaso-motor spasm. An irritation of a sensitive nerve by a sufficiently strong current of electricity, as is seen in Experiment IV, caused an almost immediate rise of the column of mercury in the manometer, this showing evidently that the vaso-motor system was intact. But, this is not all. The same phenomenon of blood-pressure reduction occurs after pre- vious section of the pneumogastrics, and similarly after division of both vagi and the spinal cord. It would, therefore, be in- ferred that pen tai causes a lowering of the ar- terial pressure mainly by an action upon the heart. The fall of pressure is not, however, so marked after previous section of the vagi, and it would seem as if peripheral irritation or stimulation of the pneumogastrics was another factor in causing the decided diminu- tion observed in normal animals. As will be noticed in Experiment II, the pulse, after a poisonous dose of pental, became sud- denly rapid,-due, no doubt, to a peripheral paralysis of the vagi (a phenomenon clearly shown toward the latter part of Experiment III); but there was noticed (in No. II) at the same time a corresponding rise of the arterial pressure,-this being subsequently depressed by another dose of the drug. There is no doubt, then, that two factors must be taken into consideration to explain 20 the fall of the arterial pressure : a direct cardiac action, and a stimulation of the cardio-inhibitory centers peripherally. The pulse.-In Experiment I, the first in- halation of io grammes brought down the pulse-rate, in a few seconds, from 132 to 102, and by the end of the inhalation, when the palpebral reflexes showed evidence of weakness, to 92. About two minutes after- ward, the cardiac pulsations returned to the normal standard, to be again reduced by a second administration of the drug. When anaesthesia became complete, apparently, the pulse-rate marked 68, and in a few sec- onds it jumped to 152,-that is, about twenty (20) beats above the normal rapidity. The effects of the drug were allowed to pass off. A third inhalation was followed by the same phenomenon : a reduction at first, and a marked increase shortly afterward,-that is, as high as 168, this increase continu- ing even after the anaesthesia had disap- peared. The same results were observed when pental was administered intravenously, as is shown in Experiments II and III. Pental, then, causes a slowing of the pulse, followed by a return to the normal, or by an increase above this point if the dose has been sufficiently large. In studying the causes of these changes, it is ascertained that the drug produces the same effects on the pulse-rate, after previous 21 Fig. A. Tracing.-Dog weighing 8.2 kilos. Injected intravenously, between x-x marks, one gramme ot Pental. Upper line represents the respiratory movements ; middle line, the arterial pressure and pulse rate ; lower line, abscissa. 22 Fig. A (continued.)-The same, half-a-ininute afterwards. 23 section of the vagi, and similarly after all nervous connection with the heart has been destroyed by previous division of the pneu- mogastrics and of the spinal cord. Is the action of pental, then, confined to the heart itself in causing the phenomenon of pulse- rate reduction ? It has been demonstrated that the drug exercises a stimulating action on the cardio- inhibitory centers peripherally, this being one of the factors to be taken into considera- tion in explaining the fall of the blood-pres- sure. Now, then, an examination of Ex- periment III shows that faradization of a vagus in an animal under the full influence of pental, produces arrest of the heart more rapidly than in normal conditions. These results are sufficiently clear. Again, when the pulse has become markedly increased above the normal point, as is also observed in the same Experiment III, electrical stim- ulation fails to arrest cardiac movements, a result similarly self-explanatory. There is, therefore, under the action of pen- tal, a primary stimulation, followed, espec- ially when the drug has been absorbed in large doses, by a paralysis of the cardio-inhibitory centers, peripherally ; this alone explaining the changes in the pulse-rate observed. When the vagi have been previously di- vided, the drug causes a reduction of pulse- rate; but though in some instances the car- diac pulsations, under such circumstances, 24 Fig. A (continued.) -The same, one minute afterwards. 25 Fig. A (concluded).-The same, one minute and a-half afterwards, at which time anaesthesia was apparently completely established. 26 may return to the starting-point, 1 have never seen them go beyond this. If the dose of pental is sufficiently poisonous, the fall of the pulse-rate, in such cases, is gen- erally progressive, with slight changes, till the occurrence of death. Just before a fatal issue takes place, the pulse is apt to become small and rapid, but these are evidences of weakness of the cardiac viscus. It is evident, then, that the primary re- duction of the pulse-rate caused by pental is due to a direct cardiac action, and to a stim- ulating influence exercised on the peripheral cardio-inhibitory centers ; the secondary in- crease above the normal mainly to paralysis of the latter ; and the final fall to an action upon the heart itself. I made a few experiments on the heart of frogs, but the results, though apparently similar to those obtained in dogs, were not very satisfactory. The mammalian heart is decidedly affected by pental, and I found that in many in- stances the organ, after death of the animal, failed to respond to mechanical or electrical stimulation. Usually death wras caused by pental through cardiac paralysis, although sometimes the respiration and the heart stopped simultaneously. The Blood. - At no time were there noticed any marked changes produced upon the blood itself, as the result of an action of pental. 27 EFFECTS ON THE RESPIRATION. Fental, whether administered by inhala- tion or intravenously, usually causes a marked increase in the rate of the respira- tory movements, as well as in their depth, although the latter phenomenon was not al- ways well marked in my experiments. The increased respiratory rate occurs similarly after previous section of the vagi, showing that the action of the agent is directly on the respiratory centers in the medulla ob- longata. But pental, so far as my observa- tions go, cannot be considered as a respira- tory stimulant in the true sense of the term. Large quantities of the drug produce, ul- timately, a depression of the respiration, and sometimes pental causes death through failure of this function. The disturbances ot respiration before the occurrence of a fa- tal issue are sometimes manifested in the production of the Cheyne-Stokes type of movements,-this phenomenon, when it does occur, being almost surely the pre- cursor of death. Though not entirely in accord with my own observations, Rieth- Tiebingep, (*), in a recent study, states that the respiration is more affected by pental than the cardiac action ; but the author adds that the respiration is stopped at first, it then becomes stormy and rapid, becomes grad- ually quiet and slow, and more superficial. -I may state, in passing, that among * Beit. zur. Klin. Chir.y Band X, Helt I., 1893. 28 other noticeable effects produced by pental, there was observed a marked dilatation of the pupil, and sometimes a tendency to te- tanic spasms. Clinical Uses of Pental. The clinical uses of pental are few and far between ; in fact, the drug has been em- ployed so far as a general anaesthetic only, as a substitute for the other well-known agents possessing such powers. The litera- ture of the subject is meagre, and yet the evidence brought forward by several clini- cians is somewhat contradictory. Let me again refer to the experience of Weber (*). This investigator used the drug as an anaesthetic in the Halle Clinic in over two hundred (200) cases. In a few of the chlorotic or hysterical patients there was a moderate stage of excitation. The excite- ment was great, however, in the case of a chronic alcoholic drinker. In a few instances there were noticed slight tetanic spasms in arms and legs. No untoward after-effects, such as headache, vomiting, or even ma- laise, were noted, nor were there observed any changes in the pulse or respiration. The corneal reflexes disappeared late, and in some cases the pupils were widely dilated. There was no salivation, and laughing oc- casionally occurred. In some cases the * Lee. citat. 29 anaesthesia continued for a short period of time after the patient had regained con- sciousness, and enough to allow the author to remove another stump of a tooth without causing pain. Usually five to ten grammes were sufficient to produce anaesthesia in from two to three minutes. The pental was used in minor operations, such as the ex- tracting of teeth, opening of buboes, ab- scesses, whitlows, etc. In the case of fixed joints, however, the narcosis was not deep enough to relax the muscles involved. According to Breuer and Lindner (*), the chief action of the drug is that of an anaes- thetic, and it may be administered in the ordinary way from a mask, or even from a pocket-handkerchief. The after-effects are said to be slight in most instances, though in some cases dizziness and trembling of the extremities may occur. In two of the cases observed by the authors, the patients cried after the operation, but could not give any reason for so doing. Narcosis was gener- ally established in from i to i% minutes, and in children sooner than in adults. In the cases reported by the authors, the short- est time for the production of anaesthesia was 40 seconds, and the longest 31 minutes. Alarming symptoms were noticed 111 one case. In two, erythema was produced. The pulse was not affected in an unfavorable manner. For slight narcosis, 75 to 150 * Wiener Klin. Wochensehrift, ]une 22, 1892. 30 grains (4.-38 to 8.75 gme.) of the'anaesthetic were used ; for the deepest narcosis about 1 ounce (27.9 gme.). Although no unpleasant effects were pro- duced, the writers believe that, as with chlor- oform, great caution should be taken in ad- ministering it. They conclude, from their clinical observations, that pental, while it will not bring-about such deep narcosis as does chloroform, will produce it sufficiently to permit of major, as well as minor, opera- tions being performed ; and further, that the narcosis occurs rapidly, disappears quickly, and is not followed by ill after-effects. And yet Kramer (*) affirms that-out of the 101 cases of pental anaesthesia, occurring in the experience of Breuer-in one, artificial means had to be resorted-to in order to bring the patient back to consciousness! Hollander (f) believes that for short op- erations, especially for the extraction of teeth, pental is much superior to bromoform, ether, or chloroform, and that it is exceed- ingly safe. The author emphasizes the en- tire lack of all disagreeable feelings on awakening from pental anaesthesia. According to Paschkis (|), pental can be administered in the samejway as ether. The first effect is that of excitation, then con- traction of the various muscles, and even * Centralblattf. Chirurg.,tHo. , 1892. t Therapeutische Monatshefte, an., 1892. t Centralblattf. d.g. Therap., Feb., 1892. 31 opisthotonos may be produced in some cases. The corneal reflexes disappear late, but a stage of analgesia occurs early, which can be made-use-of for minor operations. Narcosis comes in from i to i% minutes, and lasts only so long as the administration of the drug is continued. The recovery of the patient is pleasant and prompt ; and yet the author further remarks that a staring countenance, difficulty of speech, and a stumbling gait, lasting for a few minutes, are observed. Sometimes a slight redness of the face is seen during the narcosis. The same writer refers to two cases of death produced by pental. C. G. Velez (*) employed this anaesthetic in 108 cases of minor operations, especially of a dental nature, with apparent good re- sults. In cases where it was necessary to keep the patient under the influence of pen- tal for a considerable time, consciousness was allowed to return and then the drug was again administered. After this procedure, x/2 minute only was required to induce a complete narcosis. It is stated that in one case pental was thus given three times in 30 minutes ; and two hours afterward the patient, a man, 28 years of age, was able to walk home by himself. The only disagree- able after-effect noticed was a feeling of in- tense drowsiness during the remainder of • Revista de Medicina y Cirugia Prdcticas, Feb. 7, 1895; Brit. Medical Journ., March 18, 1893. 32 the day. The author affirms that 15 centi- grammes (about 2.3 grs.) given on a mask filled with coarse wool will produce narco- sis in one minute ; and that instead of losing its effect, the drug seems to act better on the same individual at each successive ap- plication. In some cases, insensibility is absolute, but generally, however, con- sciousness is not entirely lost. The pulse is at first accelerated, but soon recovers its normal condition. Velez adds that patients will take pental repeatedly without the slightest repugnance. Being inflammable, the drug should not be used at night. According to Rieth-Tiebinger (*), patients awaken quickly from pental narcosis; it lasts, at most, five minutes, even when deep. The patients, shortly after awaken- ing, are in a state of intoxication ; they are confused, although unaware of what has happened during the narcosis. Their speech is stammering, their gait staggering. Some patients are excited; a few complain of headache, others of weakness in the legs,- but all this for a short time only. The odor of pental is unpleasant both for the patient and the anaesthetizers. The author advises caution in pental narcosis,-its dangerous effect consisting in the cessation of respira- tion shortly after the appearance of anaes- thesia, followed by a secondary cessation * Loe. citat. 33 of cardiac activity. He concludes from his experiments that pental is, for short opera- tions requiring no complete muscular relax- ation, an available, but by no means harm- less, narcotic. This experimental and clinical evidence, incomplete as it may be, shows that pental is not entirely free from danger, and that the careless use of the drug may bring about fatal results. Further investigations are wanting in order either to place pental on the list of good and comparatively safe anaesthetics, or to discard it entirely as a worthless and dangerous agent. I, myself, shall not, for the present, at least, recom- mend pental as a safe or an efficient general anaesthetic, and until further and sufficient clinical evidence of its usefulness is brought forward, I shall continue to regard it more as a chemical curiosity than as a valuable therapeutic agent. The conclusions which I have been able to draw from the preceding study, may be summarized as follows : 1) Pental possesses general anaesthetic properties. 2) The local anaesthetic effects produced by the drug are feeble. 3) Pental anaesthesia is rapidly estab- lished, but it also quickly disappears. It is chiefly of centric origin. 4) Pental depresses the circulation to a dangerous degree, causing a fall of the arte- 34 rial pressure and of the rate of the pulse, the latter phenomenon being followed by an in- crease even above the normal standard. 5) The lowering of the pressure is due to an action upon the heart and to a stimula- tion of the peripheral cardio-inhibitory cen - ters. The vaso-motor system is apparently not affected by the drug. 6) Under pental the pulse-rate is decreased at first, due, similarly to a direct cardiac in- fluence and to excitation of the cardio-inhib- itory centers peripherally; the secondary increase to paralysis of the latter ; and the final diminution to an action upon the heart. 7) The respiratory rate is increased through a direct action of the agent upon the res- piratory centers. The respiration is after- wards depressed by an influence exercised upon the same. The drug sometimes causes the Cheyne-Stokes type of respiratory move- ments. 8) Pental produces death mainly by car- diac paralysis. Sometimes, however, the heart and the respiration stop simultan- eously ; at others, a fatal issue is the result of respiratory failure. 9) The drug, in poisonous amounts, di- minishes to a certain extent the irritability of the cardiac muscle. 10) Pental dilates the pupil,-this phe- nomenon being probably of centric origin. 11) The narcosis of pental is not unat- tended by unpleasant after-effects, the na- 35 ture of these being principally that of ex- citement. 12) Pental cannot be considered as a safe or even as an efficient general anaesthetic, and is certainly inferior to ether and chloro- form. Galveston, Texas ; 1320 Avenue E. 36 Issued Monthly. $2.00 per year. American Medieo=SurgicaI Bulletin A JOURNAL OF PRACTICE AND SCIENCE THE BULLETIN PUBLISHING COMPANY, 73 William St., New York. EblTOKIAL STAFF. WILLIAM HENRY PORTER, M.D., Chief Editor. 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