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mrri':- -- t ,imsH 1 >L JOUINAI. f March 4, 1944 HAZARDS OF CLOSED-CIRCUIT TR1LENE ANAESTHESIA Biutish NIidu'al Journal 3(9 ^^trongly in j there must iia (Case 13) eloped well- UZARDS IN THE USE OF THE CLOSEDCIRCUIT TECHNIQUE FOR TRILENE ANAESTHESIA BY S. CARDEN, M.B., D.A., D.P.M. is trichloro- jyithin the past two years trilene (trichloroethylene) has been umption that goeasingly used as a form or genesal anaesthesia. It has he soda-lime jjftain advantages over ether anil cyclopropane, such as non d. On two -flammability, and it is regarded as safer than chloroform, i the use of ,, mere is much less risk of ventricular fibrillation. When followed by lijthenny is necessary, particularly in the region of the head ven nine and ,nd neck, trilene commends itself as a suitable non-explosive lcsias respec- aesthetic agent. As a rule 1 have limited my use of trilene On another ,, thyroid and breast operation cases. Its use in a ciosed- :e succeeding -jrcuit machine appears to fall in line with what is almost alsies. Four ' routine practice of most anaesthetists--that is, the carbon td meanwhile Uoxide absorption technique for inhalational anaesthetics, re associated [here are many advantages of such a method, the outstanding and of these I,* being that a quiet operation field is ensured by the t. It should jiminished respiratory excursions. In cyclopropane anaesthesia lly "rested" his technique is of course essential for practical and economic use of coq- jonsiderations. The purpose of this paper is to show that it the intervals ' dangerous to use trilene with a closed-circuit technique. e anaethesias to have been Illustrative Cases nts who were d to this risk, iptoms would libility. Such Case I---Mrs. A., aged 67, a frail thin woman, was a poor risk W operaiion for stone in the hepatic duct. On Nov. 22, 1943, she given premedication of omnopon gr. 1/6 and scopolamine 1/300; then pentothal g. 0.5, followed by endotracheal cyclo* *pa.ne_. TTUhe* oApMevrmaiiirotnn llaacsitAe/d1 111) hhnonurrcs, Hdtuinrinnegr wwlhviiochh eshne* uwibaes 750 c.cm. of plasma. No trilene was used in this case. The months later, me apparatus, however, had been employed to administer trilene ention to his g. a patient immediately preceding this one. In the evening follow- #s hmaavye have been operation her temperature was 99" F. and she vomited itpcatcdly. This vomiting started 12 hours after operation and fs may help ^aiinued for three days, when she first complained of difficulty in sallowing and numbness over the face. She was seen by Dr. Wilfred titrris on Dec. II, and I ant indebted to him for the following sing trichloro- ^urological notes; "Slight diplopia in all directions. Left third though many Utrve shows partial ptosis, and the left pupil is sluggish. There is > three hours. ^lateral slight weakness of both external recti, with homonymous d. jiplopia. The voice is markedly nasal anil there has been nasal gurgitation, and the right soft palate is obviously paretic. Fifth nc'rve:--There is total anaesthesia to pin-prick and even hand pres- jire over both first divisions, and the right second division, including wing general hard palate. The left second division is totally analgesic to were mainly piu-prick, but hand pressure is felt on the cheek. Moderate analgesia th, tenth, addition and was [f third division on both sides, mostly on the right. Total motor inky, with complete jaw-drop, is present. There is loss to taste ,ier the right second division on the palate, but taste on both sides tongue is fair." , but all chine. were fhis patient had ,|.esia) on Dee?*2<> to have because a gastrostomy (under local anacsof the inability to swallow. The cen soda-lime pirostomy tube was removed after five weeks (Jan. 31, 1944), production o( ,pd she is now- swallowing food reasonably well. Although (Kf general condition has vastly improved, the fifth and other >xic to rabbits, wrve palsies show slight improvement only. ra of all cases, Case 2.--Miss B., aged 50 ; operation, Dec. 6, 1943--local excision t is concluded ^benign tumour of breast. Premedication,* omnopon gr. 1/3, ade trichloro- .opokiminc gr. 1/150, pentothal g. 0.5 in bed were followed by a possibility o]f try short further induction writh cyclopropane and by nitrous oxide, wygen, and trilene, using the closed-circuit technique. The duration ns only 20 minutes. About 12 hours after the operation vomiting Donald Hunter, . Cox for mncli pried; this continued for ppperatttrc was 99*. and 36 hours On the evening of Dec. 7 the lasted two days. In the early morning Dee. 8 she complained of double vision, stillness of the face, and yffieulty in swallowing. Dr. Harris saw her on Dec. II, and 557, (ported: " She has a bilateral third-nerve paresis, the right being s. sa; tactically complete. The right pupil is much dilated, with very lie reaction to light or convergence. Filth nerve:--Sill complains i ut the face feels hot and ` lingly ' over both checks (second (vision). Nearly complete analgesia to pin-prick over first and ^n'j. ttr, ,,-onii divisions of both sides, including conjunctival', and upper pats and palate. No pain on pricking the inside of nostrils. No jotor filth-nerve weakness, the masseters and external pterygoids eing strong. Little if any anaesthesia of the third division of fifth, ease of smell good. She has no nasal regurgitation, the soft palate 137, bs normally on phonation, and there is no analgesia of the barynx; but there is a suggestion of slight palatal weakness, because cannot blow out her cheeks properly." There has been only very slight improvement in this patient eight weeks after the onset of the paralysis. Both cases therefore showed well-marked bilateral trigeminal anaesthesia, oculomotor palsy, and also difficulty in swallowing, the latter symptom being more pronounced in Case 1, In the first case the trigeminal paralysis was total for the upper two divisions, with a total motor fifth-nerve palsy. In this first case, too, the right half of the soft palate was com pletely paralysed (tenth cranial nerve), and though the oculo motor paralysis was less than in Case 2 there was additional weakness of both sixth nerves. Case 1 also showed scars of recent herpes on the right upper and lower lips, which strongly suggest that a " toxin " hail affected the Gasserian ganglion. Dr. Harris pointed out that herpes frequently appears over the lips and nares after Gasserian alcohol injections. Discussion On making inquiries it was found that a case immediately preceding Case 1, on Nov. 22, had pentothal, nitrous oxide, oxygen, and trilene, via a closetl-circuit machine, for the removal of an adenoma of the thyroid ; this patient sub sequently vomited a good deal and complained of giddiness. She was seen a few weeks later, but there was no evidence of her having had any paralyses. It is worth emphasizing that Case 1 did not have trilene, and it should be noted--an important fact--that the soda-lime canister was not changed between the cases. Case I would thus have been exposed to a prolonged inhalation of any toxic products that may have formed in the soda-lime canister when the trilene had been administered to the immediately previous case. The idea that a toxic product had formed in that canister was suggested by the fact that between the dates of the first case (Nov, 22) and the second (Dec. 6) eight others were given pentothal followed by cyclopropane anaesthesia with the same apparatus, and with no ensuing paralysis. It seemed an extraordinary coincidence that on the only two days that trilene was used a patient developed paralysis. Also it was noted that only recently at this hospital, for the convenience of dispensary ordering, a change-over had been made to another well-known brand of soda-lime (B). This appeared to give very goAd absorption clinically; but it was noticed that the canister became much hotter than with the previous brand, A (sofnol soda-lime). Another point with Brand B was that when ii was necessary to change the soda-lime it was often found to be caked, and sometimes had to be dug out of the canister , whereas Brand A could always be easily shaken out. This led to the conclusion that Brand B, though it gave very good absorption, was the more hygroscopic. Accordingly, a full investigation, and analyses, of the soda-lime, trilene, and cyclopropane were started, and Dr, H. E. Cox kindly undertook the chemical analyses. Results of analyses of the two brands were: A (Solnot) 11 Calcium hydroxide 84.1 % 77.6% Sodium hydroxide Carbonate (calculated ax Na;Cl>i) Moisture 1.2% li.2% 4 8% 3.4% 7 4?:.............................. 3.0% Equal quantities of the two were then exposed in a moist atmosphere at room temperature, showing: Water absorbed after 18 hours .. 66 A I) 0,54% ....................... 2 23% ,. 1.38%....................... 6,77% It will be observed that the clinical finding that Brand B has a greater avidity for water is confirmed. Also, it is particularly important to note that the caustic soda content of B is more than 9 times that of A. The significance of the latter point is discussed shortly. In his analysis Dr. Cox found no evidence of any deleterious substances in the cyclopropane or trilene ; but experiment showed that, whereas when cyclo propane was passed through soda-lime no reaction occurred, with trilene through soda-lime a reaction took place, producing a distinctive sour smell. This reaction took place slowly at room temperature and rapidly at blood heat. As I have personally recorded temperatures of 110 F. using Brand A soda-lime and 178 F. when using Brand B in the canister of a circle absorber under conditions of anaesthesia, it will be readily understood that any chemical interaction will almost certainly be considerably speeded by this increased warmth. Trilene is itself very reactive, and is a derivative of acetylene, which chemically is one of the most reactive compounds T SL 034041 3 20 Mm,. ii 4, I9M HAZARDS Oh CLOSED-CIRCUIT TRILENE ANAESTHESIA MfMC4; known. I'll, ( n\ .ilw) pointed out that trilene with -.oda-litne produce- new and potentially tonic products, one of which is didiloroacetvlciic fins is easily oxidized to jiliospcnc and caiiron monoxide. cun cci ,, _---- > ----> in -j-NaCI + lLO CC!. NaOll C.C1 Trilene heated with alkali produces dichloroacetylene, and experiment shows a recognizable formation of this at even 98" F. If the heating is continued in the open, the dichloroacetylene, being very volatile, disappears, but if a condenser is used the dichloroaeelylene accumulates and there is an explosion, producing, phosgene. But when an excess of trilene vapour or an inert gas is maintained, dichloroacetylene does not further oxidize, and no explosion or phosgene formation occurs. This explains the fact that experimentally no phosgene reaction occurred in the circuit of the apparatus. The dis tinctive smell noted above is almost certainly due to the forma tion of dichloroacetylene, the physiological activity of which is at the present time unknown, and it is dismissed in all the literature as spontaneously explosive. The fact that Brand B soda-lime is shown to contain more than nine times the amount of caustic soda, that it is more hygroscopic, and that it generates more heat under anaesthesia supports the clinical observation that this brand would definitely be more reactive towards trilene, with the production of toxic oxidation substances. This view is supported by the clinical evidence that no case of paralysis occurred while Brand A of soda-lime was used at the hospital ; and no case occurred when employing my own apparatus for closed-circuit trilene anaesthesia, in which Brand A has always been used. The high temperature generated by Brand B soda-lime, and therefore of the inhaled anaesthetic gases, is of further disadvantage to the patient ; it leads to excessive sweating and capillary engorgement (Hewer, 19421 even at 104" F. Conclusion The relatively low incidence of post-trilcnc paralysis is. according to the above facts, due to three factors: 1. Foriunatcly, the vast majority of adminisir.Mions with this anaesthetic agent have been given in an open circuit. As there is no evidence oT diicct formation of oxidation products in the trilene without soda-lime, it seems that there is no appaieiit tisk when irilene is used in an open circuit. 2. The high temperatures generated and recorded in the canister of a circle absorber during anaesthesia have been at the point of maximum intensity of reaction, usually after the soda-lime has been in use for about'an hour. If the soda-lime has already been in use for some time we do not get these very high temperatures, which are an exciting factor in the oxidation of the trilene into toxic prpducts. 3?T"lic actual amount of caustic soda available for this chemical reaction with the trilene has been shown to be considerably higher in some brands of soda-lime. It appears to be the most important factor--apart from the rise in temperature--for this eflcct on the trilene. McAuley (1943) describes three cases of bilateral trigeminal anaesthesia, and it is to be noted that in every case the closed- circuit technique had been used, l.cngihy anaesthesia does not seem to he necessary for full toxic effect. In his cases the durations were 20 minutes. 30 minutes, and 1| hours, and in one of my cases the anaesthesia lasted only 20 minutes. Summary Evidence is brought that trilene anaesthesia in a closed circuit is dangerous, and may result in trigeminal and other cranial-nerve palsies. The palsies arc disabling and may be pcimancnt. This danger is shown to be due to toxic oxidatioq products formed by the interaction oT soda-lime and trilene. This reaction is speeded by the heat generated in the soda-lime. The exact caustic soda content and hygroscopic properties are shown to vary in dilTcrent brands. This, it is indicated, is an important factor in the occurrence of these cases. My grateful thanks arc due to Dr. II. F,, Cox for his help in these investigations. I also wish to thank Mr. Lancelot Bromley for much encouragement and for many helpful discussions. References Hewer, C. I :inptnn (1942), Recent Advances In Anaesthesia* 4ih ed., J. and A. Churchill, London. McAuley, J. (1943). British Medical Journal* Z. 713, INTELLIGENCE AND REASON CONCEPTION J. A. FRASER ROBERTS. M.D., 02 M.R.C.P., F.R.S.Et!. Director, Burden Mental Research Department, Stoke ` Bristol: Temp. Sure. Cmtlr., R.N.Y.R.; Consultant. Statistics, Royal Nary Many studies have shown that there is an associaji season of birth, or of conception, and inlelli; evidence has recently been ably marshalled by himself the contributor of the most substantial Children whose time of conception is centred on months are on the average somewhat more iot those conceived during the other half of the analysing the results of the various investigsb naturally show a certain amount of difference inT selects for contrast (with suitable reversal in thfi Hemisphere): (1) birth months May to October, approximately to conception months August (2) birth months November to April, corresponJ matcly to edneeption months February to Julyfalling into these two groups will for conciseness ' in this paper as winter and summer children resr The Alternative Explanations . ^ Two explanations of the difference are possiblejji season of conception influences intelligence ; or, " intelligence influences season of conception, Nj*i remarkable fact that, with one partial exception|(t 1 am familiar with the literature), every invest^ assumed without discussion that the first explanatibfti the correct one. Some of the hypotheses advanced! " the range of orthodox biological opinion--for e: "the higher metabolic level of parental prolop!*1 during winter cold seems to be transmitted through plasm, and to exert a lasting effect upon the future the offspring." There would seem to be nothing unlikely, however, in the assumption that the prenatsl mem of the developing child is more favourable * as compared with another. This would he an addition to the list of known non-genetic prenatal such, for example, as the well-known effect of maternal age in mongolism, or the effect of being-* child in congenital pyloric stenosis (Cockayne 1943). The partial exception to this unanimity of opW< vided by Huntington (1938). His observations on sU as highly gifted persons have led him to postulate * season which is different from that indicated by the I studies. He is concerned to explain the discrepancy, (p. 325): " It seems highly probable that the thrqe ^ mentioned--namely, the passionate, the unintelligent*] weak-willed--contribute more than their proportion*# the excess of births which still occurs at the her animal rhythm. We should expect many of the such parents to have low intelligence, and they suffice to overbalance the unusually bright children*] born at the same season, thus giving a low average regard to his main thesis, however, he is convince^ season which affects intelligence. Thus he state*; " Our new knowledge as to season of birth can bp use only if w*c use it in one of two ways. First, iif the present seasonal distribution of births. Secoiji discover the exact conditions which' make cert favourable, and then take steps to create those other seasons." ' I "j|| Practical Importance of (be Probk Apart from the theoretical interest of the practical importance of deciding which explaialjj right one is not inconsiderable. Many writer^ argument to its logical conclusion and urge th^' of season of conception would aid in human/ choose one example. Mills (1941) sums,VP 5^1 findings reported in these pages have a ,very"4 SL 034042 OCCUPATIONAL EXPOSURE OF OPERATING ROOM PERSONNEL TO TRICIILORETI1VLENE Tiiomas H. Corbett, m.d., Glfnv C. Hamilton-, b.s., Myunc K. Yoon, xr.n., and Jody L. Endues, b.s. Introduction TmciiuiF.Ttm.i:Nt' is unique among anaesthetic agents in that it is also used widely as an industrial solvent. As a result, chronic toxicity studies of TOE have been performed in greater aim unts than for other anaesthetic agents. The threshold limit value for TCE lias been set at 100 ppm. In 1970, Stewart et olreported ten experimental human exposures to TCF,, 100 and 200 ppm, for periods of one hour to a five-dav work-week. The oulv trouble some nyonse was a sensation of mild fatigue and sleepiness in five subjects during iiie fourth and filth consecutive days of exposure to 200 ppm. Following single exposures ol 200 ppm for one hour and 100 ppm for four hours, TCE was detectable m end-expired air <>f subjects for 44 and ,3S hours, respectively. A recent study by Salvini ct nl.'- has demonstrated that 110 ppm TCE adminis tered to volunteers for four-hour periods resulted in a significant decrease in per formance of standard psyehophvsiological tests. These authors suggest that the recommended TLV appears very close to the concentration capable of interfering with psychophysiologicul efficiency, even in the absence of other undesirable sub jective or objective manifestations. In light of these findings, we determined the range of concentrations of TCE in the operating room during administration of TCE anaesthesia under usual working conditions, and measured end-expired breath levels of TCE in patients following TCE anaesthesia and in anaesthetists following administration of anaesthesia. Methods Trichlorethylene anaesthesia was administered to six patients for periods ranging from 7,5-160 minutes using a non-rebreathing system with a Sierra valve. A total gas (low of 9 L/inin was used. TCE was administered using a Vcrnitrol vaporizer, with concentrations ranging between 0,25 per cent and 1.0 per cent. TCE concentrations were measured in parts per million, using a Beckman GC 72-5 gas chromatograph with a flame ionization detector. The limit of detection was 10 ppb. Opera ting-room concentrations were determined in five separate areas of the iperating room. Operating-room air was collected bv slowly withdrawing samples nto a large gas-tight syringe. Samples were injected into Saran hags and taken to From T!'e Dcpiirtnimt of Ait.tC'tliusinloi'y* University of Mtcliii^in Mediv.il School ,iml V S. 'fti-j.iio Administration Hospital Ami Arbor, Michigan 48105, t'.S.A. (575 laiiaci. Auacsth. Soc. J., veil. 20, mi. 5, September 1975 SL 034043 676 can uian anaesthetists'socnriv touhnai. TAIIU-: l Conli ntkahuns in' Tmu'iii.omi-tiivi.knh !>. mi: Oi'ekahn', Room I'f'.M Trichlorelityicnc laieatioil Oil min fill lain Directly over valve H'j One foot from take [4'| Two feet from vuhe j4'| Fool of O.K. "t'alilc (.1'J Corner of room |.V| Ranee Mean Ranee Mean Ranee Mean Ranee Mean Ranee Mean 1 l-U(ti) .1 . vr>) 0s 1) Vi `litij o 1) *_M) 7(V o ; .10 1 o 4fm 1 ,`J 0, 1-0,0to) 0.7 il.2-0.,S(o) O C) Cniuenir.it ion- of TCK in \ ..rioiis infUiimN alter ,uui U) minute' of .iitaeialieMa. Nmiilit'is in paienihi-e". iniln.ito inimli'r ol in e.icli jirnup. Niimlior in hr.ii'ket- milii'.iie Inielii .ilimi' llnnr.it wlinli -ample* were taken. Die two liielm-t le\a|-, SI ami lull ppm, nn'iirrul ilurine ,i ra-c where the aiue-tlietisl anil anae-tlictie tnatliinc were partially cndu-eil in a lent of snryir.il ih.ipes. the laboratory for analysis. Samples were taken directly above tlie expiratory valve, one foot, and two feet from the valve, all at levels four feet above the floor. In addition, samples were collected at the loot of the operating table, and in the far corner of the room away from the anaesthetists and five feet above the floor. Samples were collected at 30 and 60 minutes following induction of anaesthesia. The air turnover rate in the operating rooms was 12 times per hour. The rates of excretion of TOE were determined in three patients and in three anaesthetists by measuring concentrations in end-expired air of subjects at intervals following exposure. Samples were collected in bantu bags. Subjects were instructed to inhale, exhale about two-thirds, and then breathe into the bag. Results Operating room air concentrations of trichlorethylene ranged from 0.2 ppm in the periphery of the room to 10.3 ppm at a level of four feet directly over the expiratory valve. Average concentrations in each area measured arc listed in Table I. Three patients had detectable levels of TCF, in end-expired air for 4, 11, and 12 days following TCF anaesthesia for 30, 100 and 160 minutes, respectively, as shown in Figure 1. Three anaesthetists had detectable levels of TCE in end-expired air from 2 to 7 hours following termination of administration of routine clinical anaesthesia rang ing front 60 to 150 minutes induration (Figure 2), Discussion The study by Salvini ct ol. raises the tpirstiun of another possible occupational hazard in the operating-room environment. Does exposure to low levels of anaes thetic gases impair judgment and ability to react rapidly when the situation min >) t<:,) > !)('.) ),!'(*>) ili-i. Hi i i'.u'Ii mplfs 'iiH> a ( i.iPy piratory valve, e tlir floor, III and in tlic far live* the floor. >f anai'sthvsia. s and in three t ts at intervals . t re instructed COHHF.TT, ct a/.: r.-vosmr to TmcnuMtKTirvu-xi-: 1000,00 p 70000 - PATIENT BREATH DECAY CURVES 50000 - TRICHLOROETHYLENE 30000 <L 200.00 - 100.00 - 30minuies 677 m 0.2 ppm in `ctly over the ale listed in r 1. 11. and 12 vely, as shown iir from 2 to 7 exthesia rang- iieennational els ol anaesthe situation Ficum; 1. Trichjorcthvleiic breath decay curves fur three patients exixisetl to TCE anaesthe sia-30, 100, 160 minutes. requires it? Our study of operating-room levels of TCE during anaesthesia has demonstrated that these levels are readied near the expiratory valve during eases when the anaesthetic machine and anaesthetist are partially enclosed in a tent of surgical drapes. Furthermore, 110 ppm was the lowest level studied hy Salvini etal. and the concentrations impairing mental func tions mav he eonsidcrnhly lower. The* possible impairment of psvvhnphvsiological function hy operating room concentrations of other anaesthetic gases should ho studied. 1 * GTS cwnhinn w.vrsTiunisvs sncirrv jouhnai. Ti: U.K PF.LVIC tion of ments procedi: [n si and cu: patientpitaliv.: the foil' Wliei pelvic \ Ficl'iie 2. TriL-iiliifftliyli'iif -hri-ath ilcca\ curves fur .in.u-.thc-ti.sts fullmvinj; occ'tip.itional esjHisures cif fit), 120, ami 13(1 minutes. RHSIAN IF, Nous avons mesiire les concentrations tie Iriddorethvlene atissi bien dans l'atniosplii-re tie la salle d'operation el a la {in tit* l'expirution ties anesthesistes ati cours et a la suite tie radmiuistratiun tie Iridilnrellivlenc. T.a concentration la plus elevt-c de triehlorethylono dans la salle d'opeiatiun i-tait de 103 ppm (parties par million) et est survuntie durant one ancstlicsic aii l'uuestlie.siste iui-meine et la mad line a anestlu-sie etaient partiellcinent enfennes dans uiie teute avee des diamps diirtir"icaux. La plupart des taux variaient entte 2 et 1-f ppm. A la fin dVspiration des anesthesistes, le triehloretliylcne etail mesitrable jus<|u'a sept lieures apres un travail professionnel de routine. Los concentrations de ddoretlnlene a la fin d'expiration des malades smunis a line anestliesie an chloretlivlenc etaient depistablcs justpi'a on/e jours apres la fin tie l'anesthesie. Ackxonvi.koomfnts Tin's project was supported by Veterans Administration Research Funds. j > j i , nKFKItKNTFS 1. Sri-avAier, Il.D.. Dorm, II.(2,, f..\v, II.II.. rt ttl I-Ajif-riim-ntal lnmi.iit (-si'osurc- to Iri- ililiMiietiivli-Mi-. Areli Knvirim Ili-;ilth20: 0-1-71 t 1970). 2. Sai.vini, M,, Bivasciii, S., it M. Kv.it'taiiim of psychophvxioIo\iie;il functions in humans exjmscil to trichloroctln lone. Biit. J. Inclustr. Med, 2S: 293--29.> ^1971). j . After tomy p midline is intrtn insuffla. degree-lapnne dioxidincision A fI ei carbon An i unless minute- The non-g\: I'rcv; From F Hospital SL 034046 Cm.iil ` /<~/~ - <~r i '`X TM ftlTISH MEDICAL JOURNAL rtiuresiti ops U fj: pertussis,] 0 to agc\ ns in an - urinary' ms. The 1 column Usually s nil that LONDON SATURDAY MARCH 4 1944 | CRANIAL-NERVE PALSIES WITH HERPES FOLLOWING GENERAL ANAESTHESIA A REPORT PROM THE CENTRAL MIDDLESEX COUNTY HOSPITAL COM TILED BY J. H. HUMPHREY, M.B., B.Ch.* Jt which tl aspect that any iioiild be tve to be fore they , whether itrs make uthoriticv c amount Ling one Is put on apicd the \c legally; aioner in <P- 44) I has been interested interested er condi-j described! fact that is and to iys, were n," which n, though >ug of the hi be an tlegencrahes me a; n shelved oiicd that re centres1 pr babies hhat such; / irregular W cpn- fftp, while.! ynsils and ait for an a whethei' kc had a1 migraine, inline tar. wad ache," `1 MARGARET McCI.ELI.AND, M.B., B.S., D.A.* Paring a period of four months 13 cases of cranial-ncrvc nabies following general anaesthesia have occurred at this hospital. The cases occurred in three small groups, with ffrcc intervals of four and nine weeks between. Two of the jjjfcctcd persons died, while the remainder are at various Images of recov cry. The degree of severity varied from jjubjectiie trigeminal anaesthesia only to a complete picture "of encephalitis, but the main features were remarkably constant lwd readily recognized. Twenty-four to forty-eight hours after ose of a general anaesthetic the patient complained of a sense of coldness, numbness, or tightness round the lips, which in ^t cases during the course of the next two or three days had spread to involve the whole distribution of the fifth jtrve on both sides. This subjective anaesthesia was usually sssociatcd with analgesia and anaesthesia over the same area. ; ,,,d in nearly every case there was dilliculty in swallowing ^lid food owing to its " getting lost in the mouth." Three of the cases also showed motor fifth-nerve weakness. About the third post-operative day, in the majority, there appeared drcunioral herpes of the febrile type. At this time, in those - Nisons showing further involvement, affection of other cranial ' series became apparent--c.g,, diplopia, facial weakness, palatal weakness, and tremor or deviation of the tongue. In those t eases which showed improvement this began on the fifth to the l tenth day. and the milder cases recovered rapidly (almost completely in a fortnight), whereas the severer cases still had jiesidual subjective changes after five months. The herpes had disappeared by the end of ten days. On no occasion did we observe affection of the first, second (including rough testing 1 of the visual fields), ninth, or eleventh nerve, but all the other cranial iterscs were involved in one or more cases. Taste over the posterior one-third of the tongue was not tested, and the ninth nerve may have been involved. Only one patient had an extensor plantar response, and that was unilateral. None tan unduly high temperatures during the post-operative period. Six vomited more severely than we normally expect alter operation, and fisc were noticeably depressed, listless, or confused for two or three days. Three only ixrnplaincJ of severe headache. A typical history is that of Case 4. A Typical Case (No. 4) A woman aged 25 was subjected to nppcndicectomy for acute appendicitis on July 30, 19-tt. Premcdicaiion was by morphine gr. I h and hyosciiic gr. 1/150. I Ire- anaesthetic employed was ,i combination of intravenous pentoth.r! with cyclopropane and a little ether, given by closed circle with CO, absorption. The operation nas a short one and the anaesthesia was without incident. On Aug. 1 she complalncJ that she had had a feeling of coldness of the face with double vision for 24 hours. At the same time there was some difficulty in opening and closing the mouth. On examina tion the left pupil was larger than the tight. The reactions to light and accommodation were normal. There was double vision in all directions. The position of the false image indicated that the Other members of the stall contributing to the work were T. 0. 1. James, M.S., F.R.C.S.: II. Joules. M.D., F.R.C.P.: Miss S Ransom, M.R.C.S., L.R.C.I*., D.A.; \\. l'agd, M.D.; and E. D. van dcr.Wah, M.R.C.P. diplopia was of thiul-neite origin there was no nystagmus and the fundi were normal. Hypo-algesia and liypo-aesthcsia afieeted all the trigeminal field of cacti sale the conical reflexes were diminished and the jaw-jerk was depressed -hiiLgmiscular weakness alfeeling the fifth nerve could be delected. Subjectively the lips fell cold and the face numb and svvollcn. Food placed in the patient's mouth fell cold. There was bilateral facial weakness affecttng the upper and lower face. No other abnoimnhly could be detected in the cranial nerves. 1 here was no neck rigidity or retraction. The symptoms and signs remained unchanged until Aug. 2. when herpetic vesicles were found on the buccal mucous membrane on the left side of the mouth. These continued for three or four days. On Aug. 4 she complaincth-Qf jlifritMly in swallowing. A lumbar puncture performed on the Adi yielded a dear fluid tinder norma! pressure; no white cells were found. There was a gradual diminu tion in the cranial-ncrvc palsies; by Am: 11 the dilficuhy in swallow ing had disappeared, and by the lk'.h the diplopia had cleared. The scalp still felt abnormal. The skin over the foichcnd and the cheeks felt " swollen and stretched," and she complained of a peculiar tingling sensation around the nose. Tire tongue and the teeth still felt cold and numb. The pupils were equal in size and the external ocular movements were full. Hypo-algesia and liypoaesthcsia were present over the whole distribution of the fifth nerve, but around the nose stimulation with a pin produced an exaggerated reaction. There was still left facial weakness. She wras transferred for convalescence on Aug. 27. T he patient was seen again on Oct. 7. She stated that she had had transient diplopia, when tired, up to a week, before her visit. The upper lip still felt " twice its size " and the eyelids and the forehead scented heavy. Since her discharge on Aug. 27 she had noticed involuntary twitchings of both sides of the face, of very short duration. There was a slight degree of diminution of sensa tion to pin-prick on the right side of the face, alTecting all divisions, with a slight left facial weakness. No oilier abnormality was found in the central nervous system. Table I summarizes the clinical aspect of the cases. In it arc included only those which showed definite cranial nerve involvement ; but it should be mentioned that in association with them we encountered three cases of unexplained herpes developing about the third post-operative day, without com plications other than severe headache or transient tingling of the lips. The clinical features require no further vuiniuent, except that involvement was usually (blit not always) bilateral, and that in some the subjective liftli-nerve changes were accompanied by very definite changes in sensation to pin-prick and light touch. History of Two Fatal Cases Necropsies wete performed upon the two iatal eases Since Case 8 differed from all the oliiets. a brief history is given. Ca-e K This patient was a woman a-ed sj, on g_ poy, a cholecystectomy was pcrfoimed, the anaesthesia lasiiny ah- at one hour. She received premediention with morphine gr, I li and atropine gr, 1/101), and anaesthesia tpeiUolhal, nitioiis osuk, oxygen, and etiietl was maim.lined lluongli a i.aso-tiavheai tube by a t breed* circle technique. The operation and anaesthesia were1 -montli and without incident."I'ost-opeiatively she wa- omevvliat sins in ri;,til ing to consciousness, and vomited itulur mote than is us. a! Next 03') 316 March 4, 1944 POST-ANAESTHETIC CRANIAL-NERVE PALSIES British , MtDICAL JOUtHiLt day she was apathetic, and in the evening she became delirious, with twitching round the mouth during the night. On the following day she was ill and confused. I lei left pupil was larger than the right, and was fixed and inactive to light. There was bilateral (iftli-ncivc analgesia with absent corneal and con junctival reflexes. She had a gross tremor of the tongue, and marked incoordination of the arms, which was worse on the right than on the left. Her condition gradually deteriorated, and bilateral facial enlarged prostate, bronchopneumonia, and some genet al oedema the brain. ,, Histology.--Occasional small capillary haemorrhages were seeojt sections through the pons and midbrain, together with small pTM vascular collections of lymphocytes in the substantia nigra. B U(so addition to the lymphocytic cuffing. macrophages containing harrow; sidcrin were found in sections tliinugh the ccichcllum. flic uppeb part of the medulla oblongata contained occasional collections o* Table {.--Clinical Summary of Cases Age ! No. Sex Operation Date i 1 M 53 23/6/43 2 F 2' :k/6/43 3 F 19 1 24/6/43 4 F 25 ;;o/7/4? 5 F 62 30/7/43 6 M 41 7 F 45 2/8/43 3/8 '43 F 56 4/8/43 9 F 46 17/8/43 10 F 39 21/10/4J II M 74 27/I0M3 j: F 18 27/10/43 n F 35 27/10/43 Nature of Operation Rone graft Appendicectomy Cholecystectomy Appendicectomy Laparotomy Anaesthetic Duration of Anaesthesia Pent., cvclo., f),, induction---ttnlenc mamtcmimc Pent,, cyclo, O,, -F a little ether 11 hours | houi ,,M M ,, Pent., cycle O, . + a little cas-O,ether Ga\, O,, ether, " to-and-fro " (on circle machine) Pent., cycle?., Of 1J hours | hour .. Chrtlec> sicclomy Peru., gas, 0,, ether Removal of cyst- Pent., trilcne + O, mduciion--*cydo. aJenoma of breast maintenance Hysterectomy Cyclo., Oa> + a little ether i,, i ., 1} hours Cystoscopy and suprapubic cystoromv Appcitdicectoiny Evacuation of uterus; severe blood loss Cycle, 4* Oi ] hour 35 minx. 5 .. Post-op Vomiting + + - + + + i: -- - Herpes Cranial Nerves lmolvt'0 - j Subjective V 4- | \ (.<11 divv) .in.) motor Ml + | V (all divs.) and ! motor 4- j III, \ iall d.vs.). 1 Ml. X + Ml, N (all di\0. j rnatlUV ldi* + I Suhicctise ncht I V (all dfvs.i latci.il V (I and 2 divs.) R. VII - 1 III. V. VII. X, ! Ml + I V (all divs.), I R. VII i HI. v, VI, VII. j VIII - I V (-f motor), I L. Vlt VII 4- L. V. transient l. Ml Not discovered unti -1} month* late* Followed Case 2 oft table Followed Case 4 oft table Dod in coma on Postoperative <W Very severe headed*-4 R. extensof plant*/*1 resronx! Died on J6th peri operative day Under treatment fo* mya&thcnta gf**** ) Followed Case 1* table Pent. -- pcntothal. Cyclo.-cycloproparte. Gas*nitrons oxide. Oj* oxygen. Tnlenc*tru'hl'roet5o lene. weakness became apparent. During the afternoon she became stuporous, with jerking movements of the legs and arms. Lumbar puncture yielded 3 c.cm. of clear faintly yellow fluid under norma! pressure: protein, 1.70 g. per 100 c.cm.; 14 polymorphs per c.tnm. She died in coma at 10 p.m. on Aug. 6. Nectopsy was performed by Dr. W. Pagcl 12 hours later; "The operation wound was sound. There was no gross abnormality of any organ except the brain, which showed marked oedema. Cullmes of c.s.f. were sterile, and there was no meningitis." Histology (Dr. Pagcl).--There was no evidence of fat embolism anywhere in the pails examined. In all sections thiotigh the mid brain and the floor of the fourth ventricle there was marked deposi* lion of thready material in the perivascular lymph spaces (oedema). There were seen in addition a few vessels surrounded by a single row of lymphocytes, and a few capillary haemorrhages into the perivascular lymph spaces, together with collections of microglia in the neighbourhood of vessels. The ganglion cells in the central grey matter and the medulla oblongata were free from appreciable changes. Summary of Case.--Mmked oedema in the midbrain, pons, anti medulla oblongata. Small captllaty Itaemoi t h.iges and beginning slight cuffing around the vessels. No changes in the ganglion cells. Portions of brain ftom the region of the uflccled nuclei were remoted for animal inoculation Case II fins patient, man aged 74, tvas su" ring from retention ot mine due to an cnlaiged prostate thlood urea, If,8 mg. per 10D c.cm.) and front chronic bronchitis with emphysema. He itad auricular fibrillation, which was coottollcd by digitalis. A cystoscopic examina tion was made ;-tl suprapubic cystotomy pci formed untlct cyciopropanc-and-oxygen anaesthesia, after premedication with morphine gr. 1/6 and atropine gr. 1 lot). 1 he anaesthesia lasted about three* quarters of an hour. Postoperative ctanial-ncrve involvement was extensive but not seveie, and included the tilth nerve: subieeiive numbness tn all divisions, with hypo-algesia and piiis-aml-needles sensation over the nose Ills jaw deviated to the left. The palatal relies was absent, although palate movement was normal. The sixth nerve showed slight left externa! rectus weakness, and the seventh netvc slight bilateral lower 1 .ict.il weakness. Ilis chief dillieulty !u> in an inability to swallow solids, though he had no nasal legutgilation. Although siiinajsibic di.image was adequate he went pmi'iessively downhill lie v.a, quite unable to swallow fluids towaids the end. and died on tit-- si\u -nth post-operative day At the reciopsv. pcrlojined bv l)i, i a ,1. ilia "tiiv limluigs of signilKaiKc weie an mictoglia in stai fotmalions. Oedema was aUo present, but w* much less intense than in Case S. 1 he small haemorrhages might be due to terminal respiratory cmbnriassmcni. In photomicrograph* taken of sections from (lie two btatns the most noticeable feature ih cadi case was probably the oedema of twain and hi am-stem, although there was no clear histological evidence of the cause of the conditioh-' Other Pathological FinJincs.--Lumbar puncture was pet- formed upon nine of fhe patterns during the fust week. The pressure was never raised, and in all cases the cerebrospinal fluid was bnctcriologically sterile. In only two cases was there a small increase of polymorphs (10 and 14 per c.mm.l. In foUfi the protein content was 0.04% or less, while the remainder con tained 0.055%, 0.07%, 0.085%, 0.09%, and 1.7%. `!: Animal Inoculation.--We were fortunate in obtaining the help,: of Dr. C. H. Andrewes, of the National Institute for Medical, Research, who performed many of the inoculations. Cerebro spinal fluid from five cases and portions of brain removed necropsy from two cases (some glycerinated. some filtered through a 0.7 )> membrane and held at --70 C.) weie injected intracerebrally or intratesticularly into a total of 44 mice,-12 rabbits, and 1 rhesus monkey. No evidence of transfer of virus infection was obtained. Theories of Aetiology The eases described weie operated upon by four different surgeons and anaesthetized by three different anaesthetists. None of them showed signs of anoxaemia or other complice-, tion upon the table. Thete was no evidence to incriminate any definite ward, nut it was notable that all the anaesthetic* were given in one theatre and all on the same type of machineIt seemed to us that the damage must have been directly due to the anaesthetic or to the lighting up of some latent viru* infection, or both. 7 he mode of anaesthesia and certain sero logical findings are pi even led with these possibilities in mind. A nat-vl Ill-ties It will be observed from Table I that the anaesthetics were variable and that no one drug was common to all cases. The major surgery of the hospital is done in two operating theatres. I he anaesthetic machine used in 13 of the 13 cases is one with which either a simple semi-open " to-and-fro " method-may be used or else a closed-cuclc technique, with a sodd-lime I ru Wl to of or th is tw rt ct at T til xi c; A T O: (1 H E it et{ * a 6 3 v c r c t i i i f < 1 t t f t r t SL 034038 1944--'-: . .POST-ANAESTHETIC CRANIAL-NERVE PALSIES Medical Journal 317 i-;. ,,.iIslcrsJne>l'poral<:i1 to absorb the carbon dioxide. There is bhiy one. bottle on the machine. It contains a gauze wick. This wick'retains a little of whatever anaesthetic drug has been 70* C. in the soda-lime canister. Our suspicion was strengthened by the presence of an unusual sweetish penetrating odour frequently noted about the machine during this period. (The ' Ei Lj the bottle previously, and thereby contaminates the drug odour was subsequently reproduced by incubating trichloro i^ra text used--e.g.. ether following trichloroethylene, or vice versa ethylene with soda-lime.) fhaemo See accompanying diagram). Dr. H. E. Cox, D.Sc., F.I.C., undertook to analyse the drugs >o uppo } .lions o| !'i used, paying particular attention to possible chemical reactions or impurities. A summary of his report is as follows: (I) The cyclopropane, ether, and trichloroethylene fulfilled the prescribed conditions of purity. (2) There is no evidence of any ' El change, under the conditions of administration, in (o) cyclopropane or (6) ether which would cause injury. (3) There is evidence of reaction between trichloroethylene and soda-lime, and (4) this reaction produces dichloroacetylene. This substance readily combines with oxygen to form phosgene, carbon monoxide, and carbon dioxide, but docs not further oxidize in the presence of sufficient excess of trichloroethylene. (5) The reaction is greatly stimulated by rise of K 2 on NtTftOUJ c* temperature in the soda-lime; it proceeds markedly even at blood heat. (6) There is no evidence of direct fotmation of oxidation products in the trichloroethylene without soda-lime, (7) The effects tic 4 Ofi OtV0CN s , Although a number of tests had shown the bag and corrugated j: /Lubber tubing of the machine to be free of viable bacteria ;| ijfhen swabbed immediately after use. this machine was sent d!S| ko be sterilized in August. While it was away the same type l W circle absorber was attached to a Boyle apparatus, and I 1 r_ one case 0f paiSy occurred (No. 9), In the other of dichloioacctylcnc in trichloroethylene arc not known, hut should be ascertained. (Dichloroacetylene is a substance explosive in the presence of limited oxygen.) Experiments are at present being undertaken to find out the physiological effects of the reaction products of trichloro ethylene and soda-lime. Dr. Cox's observations have been con firmed by the Department for Research in Industrial Medicine of the Medical Research Council, which is meanwhile making investigations of the toxicity of these substances to rats. We a simple Boyle apparatus without soda-lime absorber ourselves have obtained some striking preliminary results with use<^' :lrtt* on 1^cre 'vcre n0 cascs- rabbits. The animals were subjected to anaesthetic mixtures ^ 1 }!The anaesthetics administered were varied, but all except ___ r<^ *lto were well-tried mixtures--namely. Cases 1 and 9, which consisting of trichloroethylene plus 0.5-1.0% dichloroacetylene or of ether plus trichloroethylene plus 0.5-1,0% dichloroacetylene inceived pentothal followed by cyclopropane and trichloro- given in the same way, and on the same anaesthetic machine as "Sj |kthylene. using the closed-circle technique. Ether, pentothal, was used for the cases under review. Each animal received the ind cyclopropane are drugs which have been used very KlleJtensively and have withstood the tests of time and experience. Trichloroethylene has been more recently introduced into (aesthetic practice, and has only been widely used in England I jllic Hewer's report of 400 administrations and review of ||experimental work on animals (Hewer, 1942), although, in "America. Striker and his colleagues were using it in 1935. reports of fifth-nerve palsy following the administration Ef trichloroethylene anaesthetics appeared during the past year mixture under test for three periods of about 20 minutes at fivc-dav intervals. Anaesthesia was light, and difficult to main tain when ether was not used, and ihe rabbits appeared to recover quickly and to show no untoward symptoms. After the third anaesthesia one rabbit was killed by an overdose of anaesthetic, and the other was killed seven days later by stun ning. Histology of both was very similar, and showed little change in any organ except the hrain and the liver, in which there was slight necrosis. In the brain there was extremely Eftewer, 1943 ; McAuley, 1943). In the cases reported by TW sHewer impurities in the drug were considered to be the cause. '"""Earlier reports in the German literature record cases of igeminal palsy developing in industrial workers using trichloro ethylene, toxic contaminants being regarded as a possible cause fiber, 1931 ; Jackson, 1934). Therefore, although this drug i 'mi used upon only tsvo of our cases it was naturally suspect, te help ll\lic^ j During the four months July to October 940 inhalation ^aesthetics were administered in the two theatres, of which aebror vrd at iliered' ilicied were given in Theatre I (where all the cases occurred) and in Theatre 11. Each main drug, associated with others, used in the following proportion of cases: ether 35%. marked perivascular cuffing and glial proliferation throughout, with numerous foci of necrosis. There was even a marked meningeal reaction, and the picture at first sight was one of encephalitis. We have never met such a histological picture in any other of our rabbit stock, and, although further work is necessary, have no hesitation in attributing it to the anaesthetic. On the strength of this preliminary evidence it would appear advisable not to use trichloroethylene in the presence of soda-lime. Temperature It is well known that when artificial hyperthermia is induced in normal persons a high proportion (about 70%) develop labial herpes 2 to 3 days later (Kcddic. Kccs, and Epstein, 1941). ctv 12j r of j' pclopropanc 24%, trichloroethylene 16%, and pentothal 25%. A combination of anaesthesia with oxerheating of the patient .Nitrous oxide was used in many and oxygen in all. On theby heat generated in the soda-lime might have provided a l ord* machine in Theatre I there were SO administrations of possible explanation for the herpes, the palsies, and the peculiar ;(richlorocthylene, and on the Boyle apparatus in Theatre II incidence. In a number of cases the temperature in the rubber there were 65. tubing leading to the patient was recorded, the maximum ' These figures appear to give very little clue to the problem, reached being only a few degrees above room temperature. hut the occurrence of all the cases on the circle machine led The axillary temperatures of the patients rarely varied more 05 to suspect that a possible toxic agent might result from {be interaction of traces of trichloroethylene with soda-lime 0T the other drugs used. It has been pointed out (Morton, than + 1 F. during operation. Although none of these patients developed symptoms there was no evidence to support this idea as a possible explanation. {943 ; StUbcr. 1931) that chemical reactions may occur between jichloroethylcne and alkalis, particularly when heated. Owing Virus Infection m its low volatility trichloroethylene is not regularly used on The occurrence of herpes on the third day in nine out i closed circuit, but during the period under review this was of the twelve patients who survived this period was particularly gone on several occasions (including Cases 1 and 9). It is striking in view of the fact that none of them had colds glso conceivable that in our anaesthetic machine (described or any other condition commonly associated with herpes, and were ;S jjbove) trichloroethylene used by the " to-and-fro " technique that half of them after careful questioning denied ever having The (S might linger in the machine or in the gauze wick, and thus previously had this condition. Among other operation cases n're*. ^ carried over into the soda-lime when a subsequent anaes- the incidence at that time, in the absence of colds, was very low. withW *etie was given by closed circuit. In cither case there lould be definite possibilities of chemical reactions occurring, ime'jBi'(fp6Ciaiiy since we have noted temperatures of the order of The lesions were characteristic of herpes febrilis, consisting of numerous discrete vesicles upon the mucocutaneous junction of the lips, the chin, and occasionally the buccal mucous fiti >1 iwi m `if ! .11 SL 034039] 318 March 4, 1944 POST-AN AESTHETIC CRANIAL-NERVE PALSIES 1 - -British - . Medical Journal membrane and soft palate. In four cases successful transfer to rabbits was obtained by intracorneal inoculation of vesicle fluid, and the strains behaved typically. One strain (Case 10) was studied particularly by Dr. C. H. Andrcwes and ourselves, and was adapted to rabbit testicle and skin, to guinea-pig pads, and to mouse brain. None of the strains was particularly neurotropic in rabbits or guinea-pigs, although direct intra cerebral inoculation in a rabbit produced death from encephalitis after some weeks. Herpetic encephalitis in man has never been authenticated, although during the epidemic of encephalitis lelhargica in Europe after the last war numerous attempts were made to incriminate the virus, and its isolation was claimed from the brains of the affected and of normal persons (Doerr and Berger, 1922 ; Flcxner and Amoss, 1925). Studies by Andrewes and Carmichael (1930) and by Brain (1932) showed that 70 to 7V.. of hospital patients base antibodies to herpes in their blood. In the majority of such persons overt lesions can be produced by artificial hyperthermia, intravenous T.A.B. vaccine, lobar pneumonia, meningococcal meningitis, the common cold, etc. Herpes occurs occasionally after injection of the Gasserian ganglion (Harris, 1937). All the cases showed a definite incubation period between operation and the fust appearance of symptoms, ranging from 24 hours to three days. This is very short, by accepted standards, for a virus infection. The post-mortem findings, on the other hand, were not inconsistent with an encephalitis, and w-cre comparable with descriptions of some of the findings in the encephalitis Icthargica epidemic. In the absence of a completely satisfactory " toxic " explanation, it was con sidered worth while to investigate the sera of these patients for antibodies against the herpes strain from Case 10 and another strain isolated at the National Institute for Medical Research by Dr. Andrewes. The viruses were adapted to the rabbit's skin, and each scrum was tested for its power to inhibit the production of lesions bv 5 to 10 infective doses of virus injected intraculancously. I lie results arc given in Table II. f ibll 11.--Results n! Tats for Antibodies aymnsi Herpes Case No. 1 2 3 4 5 6 7 8 9 !0 11 12 13 Herpes + a + -- + + -- + + HeriHiiic i History i 1 line of taking Serum after Operation | -- It weeks 19 6,, - .| 4 duss l .. a- No! done .n | 7 daw T - -t j --1 4 4 11 6 weeks 4 days 1 day .. Neutralizing Anti bod >e> Strain 10 M.R.C. Strain -f -i- 4 4* - 4 4-- T 4-i -t 1 It is evident that every scrum contains antibodies against both strains. The most significant samples are the early ones from patients without herpetic histories, since in these eases the formation of antibodies would have been too rapid to be due to the herpes occurring at that time, quite apart from the fact that some never developed the condition. Herpes anti bodies are commonly found in persons with latent infection, and the implication is that -all these patients had latent herpes. We were not able to demonstrate any immunological differ ence between the two strains by cross-protection tests, and cannot claim unusual virulence for the strain 10 studied. If herpes or any other virus infection is involved it must have been " lit up " by the anaesthetic. There is some experimental evidence for this possibility in the observation of Fiala (1943) that subdural or intravenous injection of vaccinia virus in rabbits is not normally followed by encephalitis, but is so if tile rabbits are under urethane anaesthesia ; or the work of Silberstein and Hotr (1925), who showed that a normally latent encephalitis virus could he activated in dogs with an lick fisiula by feeding with a diet of meat only. Argument by analogy is dangerous, however, anti in the absence of positive findings from the inoculation of post-moiiem maleiial into susceptible annuals we tire unwilling lo do moie than siigcesl the possibility that herpes virus played a pan. Discussion The clinical evidence favours two possible theories, or a com bination of both, but the experimental results are strongly in favour of a toxic theory. If the latter is adopted there must have been great susceptibility, since one anaesthesia (Case 13) was of five minutes' duration and the patient developed wellmarked palsy. ] The only drug which could be incriminated is trichloro- Vit},m ethylene plus soda-lime, and this only on the assumption that Ibreas it could have persisted in the machine or in the soda-lime *ttaiu between ihc anaesthesias in which it was used. On two occasions as long as three days elapsed between the use of the t-r-i-c--h--lo--r-o--e--t-h-y..l-e--n--e- -a-n--d- .t.i.le -a-n--a--esthetic w---h-ipchnuiweras followed by 1`Sthet palsies, and during the intervals there had been given nine and pe twelve closed-ciicuil cyclopropane oi oilier anacslhesias respee ttiacstl lively on the same machine without any ill ellccts. On another ? thv occasion trichloroethylene was followed on ilttee succeeding :'tcuit days by varied anaesthetics which developed palsies. Four rout closed circuits, but no further trichloioothylenc. had meanwhile ftoxidi been administered. Seven only of the eases were associated fherc with the use of trichloroethylene on the same day. and of these ^ two actually received the drug in elnsKf- circuit, it should lijmitii be mentioned that the soda-lime was periodically 'rested' litis tc> for any time up to two or three days, and the use of con- Sonsid, laminated soda-lime at a later date might explain the intervals * dan. between trichloroethylene administration and the anaethesias which were followed by palsies. We consider it to have been a definite possibility that the majority of the patients who were Cost anaesthetized on the circle machine were subjected to this rist. ">r op The fact that only a small proportion showed symptoms would was ui mean that there must be great variation in susceptibility. Such * - < variations ate weiltl iknown in io\ieo!ogy, tPivrOepniM The first case of the scries was missed until 41 months later, when a chance remark of the patient's drew attention to hi` lesion. It seems to us possible that mild cases may have occurred elsewhere, and the facts recorded above hate been published in the hope that the observations of others may help to shed light upon the problem. It is now over three months since we ceased using trichloro ethylene in association with soda-lime, and although many trichloroethylene anaesthesias, some lasting up to three houis. have been given, no further palsies have occurred. Summary Thirteen cases of cranial-nerve palsy following general anaesthesia are reported. The nerves involved were mainly1' in-pr the fifth and seventh, but the third, fourth, sixth, tenth, thl twelfth were involved in some cases. The condition associated with labial herpes in 9 cases. . :Jbf lot, No anaesthetic drug was common to all cases, but all weft) t administered on a circle absorber anaesthetic machine. i Evidence is given for chemical reactions between soda-lime gas(r4 and trichloroethylene in the system, with the production of, Sn(j } dichloroncciylcnc. fiber g Preliminary results show that this substance is toxic to rabbit*, nerve Antibodies against herpes were found in the sera of all cases, j i Cos The aetiology of the condition is discussed. It is concluded | fit be that until further investigations have been made trichlorov! ethylene should not be used where there is any possibility gS?,* its coming into contact with soda-lime. ' Our thanks are due to Dr. C. H. Andrewes, Dr. Donald Hunter.- IHarm Dr. C. L. Hewer, Dr. J. G Greenfield, and Dr. H. E. Cos for mud1! ifenpe help and advice. ' 'if Dt RjriRENCr Andrewes. C. H., jnd Carmichael. E, A. 0930). Lancet, 1* 857. Brain, R. T. (1932). Brit. J. r\p. Path., 13, 166, Doerr, R,. and Berber, \V (1922). Schnci:. meii. Wschr52, 862 Ftula, S. 0943), '/.bL Bakt,, 150, 260, Flcxner, S,, and Amoss. It L, (14C5) J exp. \fed., 41, 218. Harris. W, (19371. The I'atu.l Anii^i/W./v. London. Hewer. C. L. (19-42). Prov, ray. Sac. 35. 463. .-- (1943), Ibid., 36, 463 l.ukson. D. E. U`>s4V ke.Mie. I M., Rocs. K. 4/r.'.//j .t 'Im/.iM, 13, 201.nul l.pwicin. N. N. (1941). J, 4/ncr. tnrU. 4.., 11V N 16, MoAulcb. J. (1943) British McJ.ctu Journal, 2, 713. Mom,|| .1. V. (104 t> Ibid , 2, s:s SilKTMi-m. b.. ;tnd Hot!, H. (|92M. / <'\p, Mai, 44, 257. Striker, t'., et a! <!935L Jnctiii, A l/i.f/uv* . 14. 6S, Sliiber. K. (|93?i, 4nh. (!c*erhcp,ifh,, 2. 39S. difiict ireport breed &' fHvisu ccoiii i turns ftioioi being {Sense SL 034040