FACTORS AFFECTING SUIR,VIVAL OF THE GERIATRIC PATIENT AFTER MAJOR SURGERY

U AUBRY, M D R DENIS, M D M KI~i~RI-SZANTO, M D AND M PARENT, MiD o ) ' ' I

IT IS ItAI'd)LY NECESSARY to emphasize to our readers the extent tO which ana~esthe- I t]sts and surgeons m ma]or hospztals find themselves preoccupied with, the problems and challenges of surgery m the germtnc patient Not only is the num- ber of older surgxcal patients growang, but usuaUy these subleets are gravel risks than those an the younger age groups, and they demand a d]sptoportmnatel share of everybody's attention A survey of reports In the recent hterature (Table I)m

m I comprising cases of about four thousand patients from around It he world reveals that thetr problems are sttll largyel unsolw;d and that elderly, patients reqmrmg ma]or surgery continue to face a considerable risk to thetr hves , m

Since there are few comprehenmve patient groups wath such a high base-hne mortahty, we eonmdered the geriatric pattent population to beJ ideally stated for a study of the effect of various parameters on survival

WORLDWIDE

TABLE I

EXPERIENCE WITH MAJOR GERIATRI i

REFERENCE YEAR CASES AGE

1 1957 450 65 +

2 1958 307 65 +

3 1957 464 70 +

4 1961 64 70 +

5 1961 600 70 §

6 1961 700 70 §

7 1961 71 70 §

8 1964 342 70 +

9 1964 281 70 §

10 1964 395 70 §

11 1964 500 BO §

AVERAGE 379

~RE- CALCULATED

SURGERY

COUI~TRY MORTALITY RIEMARKS

. . . . . . ~. % . . . . . . . . . ,,, . . . .

AUSTIRIA 23 B IL IARY SURG ONLY "

USA 17 ABD SURGERY ONLY

SWIl lZERL 20 M A I N L Y A I B D O M I N A L SURGERY

USA 7 BIL IARY S~IRGERY ONLY !

USA 21 MAJOR SUIRGERY ONLY

GERMANY 14 MAJOR SURGERY ONLY

USA 24 M A J O R AI~D SURGERY ONLY I

C A N A D A 13 M A J O R A | ,D SURGERY ONLY

USA 26 ~ IL IARY SURGERY O N L v I

ENGLAND 26 EMERGENCY A D M I S S I O N S ONLY

USA 20 ALL SURGICAL A D M I S S I O N S

20

AUTHOR'S DATA FROM THE

*The authors are from the Depa ,r~ents of Anaesthesia and Surgery, U!mverslt6 de Montr6al, and Notre-Dame Hospital, Montr6al, Canada Parts of tins study were presented by the senior author (M K-Sz ) m a panel discussion of neuroleptanalgema at the Third World Congress of Anaesthemologlsts, Sao Paulo, September 1964, and before the Annual Meetang of the Royal College of Physicians and Surgeon,, of Canada, Toronto, January 1965

510

Can Anaes Soe J, vol 12, no 5, September~ 196b

A U ~ e t al F ~ C T O ~ ~ T ~ C T ~ N r SUP, V~TA~. OF THE C.ER~TmC PATIENT 5 1 1

MATEBIAL AND METHODSf

The terms geriatric, maNr surgery, and surw~al must be defined because they assume dtfferent meanings for d~fferent authors Our populatmn consists of patients past thetr 70th bmthday who were anaesthetmed for longer than l~hree hours, regardless of the nature of surgery, 9r who had an explorataon (as opposed to s~mple opemng) of the abdomen, thorax, or skull, regardless o~ the length of operatmn A patwnt was deemed to surv~l'e only ff he was &scharged from hospital This ~s a partacularly severe restrxct~ion m th~s age group, since many of our patients had to be retained for terminal care of their illness who, ff younger, would have preferred to return to their famdms

RESULTS

Dmmg the years 1963--64, mole than 35,000 operatmns were performed at Notre-Dame Hosplta| In round numbers, 5 per cent of all adm~ssaons to the surgical serwees (General Surgery, Neuro-Surgery, Gynecology, Urology, ~)to- Rhano-Laryngology, and Ophthalmology) were m the germtne age group, I yet only 313 operatmns qual~ed ]?or mclusxon an th~s study The operatmns were performed on 30~2 patients-7 patients were operated on twice and 2 others, three times Forty patxents dad not surwve, including one who was operated on twv~ee an over-all mortahty of 13 2 per cent when referred to patmnts, or 12 8 per cent when referred to operataons The deaths account for roughly 10 per cent ~ the serwees' total mortahty and for 45 per cent o~ the geriatric mortahty Th~s populatmn will be stuched m ~ner detml

The monthly trend m operataons and the attending mo, tahty (F~g 1 ) m&eates that the number of operataons has been nsxng steadily during the observataon period Th~s rise occurs at a rate about twaee that oti[ other operatmns performed

Z @

~@

m

0

l T -NDs operA.oN AN ii l , ~ Q ~ T ~ U T V ~ 6 3 - , , 6 4 ....

I

o | ~--o ~ . ~ - ~ ! -

FIcuaE 1 Monthly trend of operations and their mortahty, 1963-64 Sohd line Number of major gerlatn~ ow_ratlons each month wlth the best-i~ttmg stra~tght hne ealcl~lated from these data Broken hne the number of deaths a~lsmg from these operatmns

512 c~xt)mN ~U~AEST~T~S~' SOCIET~ jotnaNXL

m the hospltal We conclude that even during such a short interval the mdtcahons for surgery m the geriatric group have been widened, and that consequently, the average pahent we see today ~s a slightly poorer risk than the patient we saw at the beginning of this study With this m rmnd we can turin our attenlaon to the trend of mortahty during the same period. Since the number of deaths per month is small, the computation of the best-fitting straight line to these values zs assocuated wath so large a coefl~c;ent of vanab;hty that ;t cannot be meaningfully compared wtth the trend hne of operations It can be seen, however, that the mortahty rates keep essentially Steady m the face of the rising number of operat;ons and the increasing surg;cal rlsk status of our pahents

The age of patients (F~g 2), the duration of surgery (Fzg 3), and the, site of operation (Fig 4) are usually considered m analyses of this kmd Among our patients very httle d~fference was n!oted between the patients m the two halves of theft eighth decade and the pataents past eighty The results are probably tainted by the fact that elective surgery rs not too frequent m thrs age group The duration of surgery had 'absolutely no effect on the outcome, perhaps because, as the patients' conchtIons lrecome more desperate, the opera- tions tend to be shorter Th~s ~s supported by the high mortahty associated w~th anaesthetic t~mes of less than one hour

30 I AGE OiSTRI~SU T ~_! O- ~]

n

, , . i

< 2 0 at o

z 1o u

O-

7 0 -- 7 4

1 7 5 - 7 9 8 0 4. f _

J _ _ i! . . . .

,~, 2h ,r,,3 N u ~ s t a oF P A ~ a t N T S

FIC~RE 2 The age-dlstribuhon of our subjects In tins and m all the following figures exeep,~ Fig 7, the ordinate is marked m percentage mortahty while the numbers along the absclt, sa mark the cumulative total of patients The area of each rec- tangle ~s proportional to each group's contnbutmn to the t~tal mortahty

j,= g l

h- a 0 lO i

Z

o lU I J

L

1 ANESTM(~'aA' T,iM~S I

1 - 2 t 2 - 3 I 3 " 4 I 4 *

H U M B E R OF P A T I E N T S

F I C U R E 3

AUBRY ~ alo FACTORS AFFECTING SURVIVAL OF T I I ~ GERIATRIC PATIENT 513

@

G0 ~ T ~ C T

L g V ~

othr abc!l

$

H" LP !

2 ~ 2 ~ 7 2 ~ 7

,'T H

F ~ U ~ E 4

Our populatxon of mtracranla] and thoracic surgical patients is relatively small The rnoltahty rates m these groups might have been unduly influenced by the dermse of a few patients who were moribund pre-opr We were partlcu- laIly ~rapressed by the ease wath whach many elderly patients tolerated long and bloody neurosurglcal procedures The large mortahty assocmted with operations on the gastro-mtestmal tract ~s due to the grave p~ie-operatlve state of many such patients and to the underlyang mahgnant dasease ~tn many others

There as of course nothing new m the statemer~tLt that the preparataon of patxents for surgery wdl profoundly affect the outcome of the operation Never- theless, the extent of the effect m~ght come as a surpn,,e (Fig 5) We have classas as "emergency" those pataents an whom the operataon could not be safely postponed ~or more than six hours They include cases of bleeding, per- foratxon of a vascus, and advanced cases of intestinal obstructaon These pataents were desperately sack when s seen and could not be ideally prepared ~or surgery ]n the second or "urgent" group we included t hose pataents whose disease permatted more t~ne for pre-operat~ve treatment, up to a maximum of s= days

30

t ~

/

~L~{T6VE

~77

F~cvR~ 5

I

6

s

G

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~77 313

514 CANADIAN ANAESTI-IETI~!,TS" SOCIETY JOURNAL

Thxs group mchded fractures, chronm, partJal, or recent complete obstructmn of the large bowel, progresswe laundme, bralm tumors, and the tmplantatton of cardiac pacemakers Most of the patmnt!s recewed vigorous treatment drrected to their blood volume, fired balance, and cardloresplratory status before surgery In the "electave" group we were still left wrth some patmnts who had no real chome about undergoing surgery, such as patmnts w~th non-ob~tructwe mahg- nancms, peripheral vascular dlsease, symptomatm mcaslonal hermas, or those requiring extenswe reconstructive surge~ty In spate of this, we have lost only two patmnts from this large group m two years

From the standpoint of anaesthesm~lt ~,as, of course, most interesting to mvest~- gate the influence of various anaesthetm agents and techmques upon surwval, especmlly because a new anaesthetic aglent NLA (neuroleptanalgesm maxture) was introduced more widely m our hospital early an 1963 Our assessment of this drug combmatmn has been presented e]lsewhere, lz-14 and there have been an increasing number os commumcataons relating to this techmque from lgoth s~des of the Atlantic i~-~7 This new method of supplementing mtrous 'oxide- relaxant anaesthesia appeared to us to be well suited for germtnc anaesthesm and for the management of other poor-n,~& patmnts The raw datk (Fig 6) were singularly ummpresslve and tended to confirm a recent claim ~1 that the choxce of anaesthesm did not influence surwval an germtnc surgery Closer analys~s, however, revealed an maportant fault ,an our reasoning the presentatmn m Fagure 6 rmphes that the cholce of anae,!thetlcs was not at all influenced byl the patmnt's status, the contemplated surgery, and other slmdar c0nslderatmns If such influences were not taken into acc~,i~unt, the comparison of several groups, each selected according to a dafferent bm,~ed vmwpomt, wo~ld be without meaning or interest In our own series the asslgnment of an anaes lhetm technique was defimtely not at random On the contrary, ~t appeared thlat most of our worst-risk patmnts recewed NLA Our problem, then, was to find a statlstmal approach which could evaluate the success of a gwen treatmen~ an the absence of any vahd control group "['he present soluhon as a crude one, apphcable only when greater than 10 per cent mortahty is to be expected m the albsence of tleat- rnent and when the treatment as truly effectwe By the same token a proof of statastmal sagnd~cance by such a method should carry added wexgh!t

F m ~ 6

Atomy et al FACTOm AFFECTING SUI~VIVAI~ OF THE GERIATRIC PATIENT 515

Since elderly sick people are notorious for thetr lack of uniformity, we could not expect to collect a representatwe series of matched cases. We have assumed instead that over a period of roughly two months the hospltahzed patxent popu- lation wall average out well enough m terms of operatmns and surgical n~k to make a comparison of one such period wath another statlstxcally vahd In other words, we randomazed our data by dwldmg 300 operatv~ns into twelve consecu- twe groups of 25 operations each (the last 13 oper~litlon,, were &sregarded) and we examined the number of deaths and the use of NLA m each of these groups (Fag 7, hne 1) The negatwe correlation between m0rtahty and the use of NLA (Fig '7, line 2) is strflang and statlstacally probably slgmficant (p = 0 05) It is gratifying, though of doubtful s~gmficance, that the intercept of our regression hne corresponds closely wath the mortahty obtained ][rom the hterature

Fictrrw. 7 The effect of neurolept-analge,tla u[~n mortahty Line 1 Number of deaths and number of patlents xeeetwng NLA m consecutive groups of 25 operatmns each The eolour code divides these groups into 0--25~;, 25-50,~ and 50~; q- NLA Line 2 Correlatmn between rnortahty and the u,e of NLA m the combined groups The average mortahty gleaned from references 1-11 is included for comparison The observed negative correlation is statistically slgmficant (p - - 0 05)

The data m Figure 7 indicate that the shift fro~m other anaesthetics to w~ll account for about two-th~rds of the lmproverrptent m the mortahty rat, thas ,extent, then, at least two-th~rds o~ the deaths observed w~th convent anaesthetics m this population should be regarded as anaesthetic deaths T

NLA To

lonal his ~s

516 C.~T_~mn~N ANAESTHETISTS' SOCIETY JOURNAL

surely not so wathm the normal defimtxon of the term, that is tgsay, mortahty follovang the exhibition of these agents iS not due to some harmfhl effect of the drugs or to someerror m the anaesthehst's management of the ease,

It should be kept m mind that most anaesthetic drugs are chosen on the basis of their short action and that the ideal anaesthetic as thought to be one which would leave the patient m complete control of his homeostams as soon as the dressing of his recision is completed One might well argue, a~d it has indeed been pointed out m certain contexts, that wh~le such management is probably ~deal for reasonably fit patients, it wall leave the patient with lmalted resources m a dangerous predicament There are several factors that contribute to an increase of oxygen requirements and to a resulting increase m CO2 production immediately after awakening from anOesthesia'

1 Most frad patients wall be mtldly or moderately hypothermlc after pro- longed surgery m air-conditioned opera~mg rooms This leads _~o shlverm~ as soon as their thermo-regulataon recovers and may increase the O2 demand by as much a~ six tames

2 Pain and apprehension may by then~selves double the O2 demand Follow- mg abdominal surgery the mctslonal pare imposes a rapid shallow breathing pattern which is inefficient and, Itherefore, further" increases the patient's work-load

3 If for any reason (el below) the artertal blood is not fully saturated, a compensatory increase m cardiac output Is needed to provide the necessary 02 to the periphery. Smaflar increases Will b e caused by haemodtlutaon (a regular feature) and by increased vascomty of ~he blood, which increases myocardial work for a gwen cardiac output The ~ltualaon might be worsened by mild hypovolaerma and sluggtsh vasomotor reflexes, which are sometimes difficult to avoid in such patients !

The increased demand confronts patients when their O2 uptake is curtailed because

1 Their lungs are wrtually demtrogenated foUowmg general anaesthesia lasting longer than 60 mmutes Combined watih the shallow breat|nng mentioned prewously, this will produce disseminated alveolar collapse that may add up to mgnfficant shunting of blood across the lungs

2 In many instances the mtuatlon w~il be aggravated by depressed ciliary action mamedaately after surgery The mouth-breathing seen m most of these patients wall promote the drying of secretmn, thus further compromising the clearing of the lower mrway

It ~s noteworthy that most of the problems lust outhned are of short duration They last a few hours at the most If the patltent is left to his o~na resources to deal with them he will m most cases find the necessary reserves, even if he is m this poor-risk group However, the completeness of his recovel T and the .~ost m terms of cardmresplratory and metab0he effort remain m doubt There Is a much smaller group of patients who reach the operating table with no cardm- respiratory reserves whatever, they cannot re,,pond to the increased demands of recovery from anaest_hesm and surgery They will lapse into a vicious circle in which the cost of furmshmg O2 to their tissues and ehmmatmg CO2 ts greater

AUBBY et al. FACTORS AFFECTING SUIRVIVAI OF raE GERIATRIC PATIENT 517

than the energy-eqmvalent of the 02 furmshed by each breath, and they wili dxe m complete exhaustaon 6--48 hours after surgery OUr data can be taken to indi- cate the presence of yet a third group of pahents who may be kept out of tlhese vltc:ous circles by tamely and short-term assastiance of their resptratlons Such a,,slstance will.

1 Furmsh deep, slow breaths and thus re-establish the mtrogen scaffolding of the lungs

2 Reduce the 02 requ:rements by almost completely ehmmatmg the work oi resptratlon

3 Keep the pat:ents mildly sedated through hlyperventflatmn and pr0vlde fully hum:ddled air untal the c:ha resume their actavlty

Pro'waling such ass:stance as a prophyllachc measure and on the scale that we beheve to be useful :mphes the retentmn of er~dotracheal tubes m our patients for at 1east a few hours after surgery The only alternahve to this woukt be tracheotomy, whlch :s ruled out by the assocmted risks and nursing problems In th:s respect, NLA proved to be extremely valuable It can be fairly stud that :t presents a quahtatwe advantage over prewously avmlable anaesthehcs We have found that wtnle only the excephonal pat:ent tolerated an endotracheal tube for any length of tune after conventmnal anaesthesm, the malont y of elderly pat:ents receiving NLA would comfortably tolerate prolonged res~tra- tory assastance even when they were suttqc:ently awake to commumcate wltlh us by s:gns or by writing The mortahty for patients assisted after surgery 1~ the same as for those who recewed no such assistance m tins series (Fig 8) This result has been achaeved, however, an face of a double bins favouring surWval among the group wh:ch had no resp:ratory ass:stance, ,,race most of the really s:ck pat:ents found the:r way into the "resparato:" g:loup We subm:t :t for What at may be worth on the bas:s of our present data Further work :s now m progress to determme more exactly the O2 cost of recovery from anaesthesia and surgery and the poss:ble sparing actmn of hmated resp:ratory assistance upon fins parameter

FmtnaE 8

Needless to say, the s:tuahon m wh:ch a pahent rmght benefit from resptr~tory ass:stance after surgery does not start with his ti:lst old-age penmon cheque We cons:der that today . [al l ~ahents undergoing mallor surg yet of a body c,FLvlty may benefit by such treatment, and we are now prepared to furmsh :t for as long

518 CANADIAN ANAES ,T~TL.~]TS' SOCIETY JOURNAL

as they are not dasturbed by the endotracheM tubes It should be pomted lout that we consader NLA as the anaesthelae of choace m the management of specml- risk pahents, prmcapally because It rnake,.i, such assistance possabIr It might very well be that m the hands of those who da not avail themselves of th~s advantage, the results obtained with NLA wdl be no dtfferent from those~ obtmned wath other anaesthetacs Our rule of thumb for the re-o eratlve a ralsal o]? our a ' " P P ~ PP pat ents need for respiratory ass~stapce .after surg yer as that th se who cannot ehmb a flaght of staLrs at the tame of pre-o!peratlve rounds should have respiratory assistance tdl the morning after surgery Dmmg thas period we do not hesatate to gave them further sub-anaesthetic doses o~ NLA ff they will not tolerate the endotracheal tube otherwase By the nature of things, wath increasing age an ever larger percentage of patients Will fall into this group Fahents who are dyspnoele at rest before surgery are considered to be serious candidates for prophylactac tracheotomy, since their need for respiratory assastance as hkdy to continue ]?or several days

The plea for post-anaesthetic resplrato~y assistance has been made before, but at was restricted to cardmc bypass procedures, ~8 open chest clases, ~9 or over- whelrmng peritoneal m]?eehon, 2~ and all authors considered tracheotomy as a prereqmsate Our claara as that hmated respn atory assastance as mchcated much more often aftel surgery than has been suspected, and that it is a feasible procedure without tracheotomy when NLA is employed Our nursing staff adapted easily to this new regime and we could satisfy all demands of an average daffy operating hst of 70 cases, as well as the other demarl~ds of a 1000-bed hospital wath five respa- rators m the recovery room and an the mtensave care umt We eStamate that as a result of these changes about one patient each month now leaves lhe hospital who as recently as two years ago would not l~ave had the benefit o]? surgery or would not have surwved the operataon

SUM]VIAB'~

We have reviewed the incidence of malor surgery an genatrac patients an our hospital There were 313 such operataoinl.s performed an 1963 and 1964, with an over-all mortahty of 13 per cent Less than one per cent of all operations and only about 15 per cent of the geriatric surgery satisfied our criteria, yet these pataents accounted for 10 per cent of ~mr surgacal and for 45 per cent of our geriatric surgical mortahty

Among the various factors mvestagate, J, the sate of surgery and operating tame were found not to contrabute slgnlficantl, to mortahty The age of~ our sub]ects had some effect, and the tame available ]?gr ple-operatwe therap~ had a marked effect I I

Anaesthetic agents had no effect or~ mortahty at first sight, but when the choace of different agents was taken rot0 account a statlstacally slgmficant nega- tare eorrelatmn emerged between mortahty and the use of negroleptanalgesm This observataon as tentatwely explained by the fact that NLA makes ~t possible to assist the resparatlon of most elder]l]y pataents ]?or some tmlle after surgery The rataona]e ]?or th~s treatment and om procedure are d~scussed m some detail

~t r~ny e t al FACTOnS AFFECTING SURVIVAL OF "I!HE GERIATRIC PATIENT 519

Nous avons Stud~ les patmnts g~natrxques qm ont suba des op~ratmns majeUres d~ns notre h6patal en 1963 et 1964 Sur 313 " , operatmns, nous avons eu 13 pour cent de mortaht$ Bran que ces opSratmns reprSsentent morns de 1 pour cent de toutes les op~ratmns et 15 pour cent seulement de la chtrurgae g~natnque~ le taux de mortaht~ de ce groupe contnbue pour 10 potu cent des mortaht~s chtmr- gmales et pour 45 pour cent de la mortaht~ g~rmtnque

Parma les davers ~acteurs que nous avons mves~gueS, nous avons trouv~ qu~ le ta~tx de mortaht~ n%taat pas reh~ au sate op~ratoare m ~ la dur~e de l'op~ration Par contre ]'~ge du patmnt avaat une certame ardluence sur le taux de mortaht$ et la pr~parahon du pataent en pr~op~rato~re avast unle influence des plus s~gmfi- cat lves

Les anesth~s~ques employSs ne semb|ent pas '~tre un tfactem d'tmportance h prermere vue, mms quand ]e cho~x de d~ff~rents agents est pns en cons~deratlo , on s'apergo~t qu'fi y a une corr~lataon n~gahve sagnd}icatvce entre l'emplot de la neuroleptanalg~sm (NLA) et le taux de mortaht~ Celte am~horatmn nous p~aat due au faat que le NLA nous avaat perm,s de rmeu]x as,~aster la resp~ratmn en postop~tato~re d'un grand nornbre de nos patmnts

REFERENCES

1 K~n~LE, P Operahve Results of Bahary Surgery m Patmnt,!, ovel 65 Arch khn Chlr 287 761 (1957)

2 W~m-~rs, L F & KNICHV, C D Abdominal Surgery m the Aged A M A Arch Surg 76 963 (1958)

3 NISSEN, R Recent Advances m Genatncs Arch khn Char 287 121 (1957) 4 DE PEYSTEn, F A & GiLcmaisr, R K Current Prmclpleq, Govermng Abdominal Surgery

an the Aged A M A Arch Surg 83 154 ( 1961 ) 5 H~rtoN, P W , et al Analysas of 600 Major Ope:rahons of Patmnts over 70 Year,i, of

Age Ann Surg 152 686 ( 1961 ) 6 G~.MARLIr M & K~Atrrwm, K TH Experiences m Geriatric Surgery Z Alternsforsch

i5 106 (1961) 7 SrAmr.cm~rr L H An Analys~s of Factors Whach Influx.trice Mortahty foUowmg Exten-

save Abdominal Operatmns upon Geriatric Patmnts SUrg Gynec & Obst 113 283 ( 1961 )

8 Ro~x~s, R E & MmDL~.'roN, A G Ma]or Abdominal Su!rgery m Patmnts over 70 Years oJf Age An Analysas Canad J Surg 7 19.9 (1964)

9 LOm~AN, P H, et al Factors Influencing Mortahty following Anaesthesm an Gallbladder Surgery Anesth Analg Curr Res ,$3 708 (1964)

10 FlaY, H ~ H Mortahty an Emergency Smgmal Admassions over the Age of 70 Years Brlt ] Surg 51 837 (1964)

11 MARSHALL, W H & FAH~-Y, P J Operative Comphcatmns and Mortahty m Patients over 80 Years of Age A M A Arch Surg 88 896 (1964)

12 K~m-SzANTo, M, TE~.MOSS~, F , & Tno~,, D Anaesthe~m Tame Dose Curves V Data on Neurolephc Drugs with Remarks about their Actm,]n Canad Anaesth Soc J 10 484 (1963)

]3 CAr~GNaN, C, et aI Innovar~ Farst Experiences with a new Intravenous Anaesthetm an a Teaching Hospata] Anes Analg Curt Res 43 550 (1964)

14 A~ay , U, et al NeuroleptanaIgesla Analysis of a Persorml series of 1007 Cases To, be pubhshed

15 HoLDr~m~.ss, M C, CnAsr., P E , & DRIPFs, R D A Narcotae Analgesm and Bu~rro- phenvn with Nitrous Oxide for General Anaesthesia Ariesthesmlogy 24 336 (1964)

16 CORSS~N, G, DOM~O, E F , & SW1~ET, R B Neur(~Ieptanalgesm and Anaesthe]sm Anes Analg Curt Res 43 748 (1964)

520 CANADIAN ANAESTHE~"ISTS' SOCIETY JOURNAL

17. NmssoN, E Ortgm and Rahonalb of Neuroplept-Analgesra Anesthes,ol0gy 24 267 (1963)

18 D ~ N , J F Ja The Importance Iof Controlled Ventdahon f011owmg Open-Heart Surgery. Intemat Anaesth Clan 55 (1963)

19 N o ~ D ~ a , O P Ettoloffv and Treatment of ResDtratorv Insu~ezeney Concept of Respiratory Work Mmerv"a aneste~lol �9 el. Sm'v Anae'sthesiol 8:178 (1964)

20 BvRrm, J F , PoreroPPWAa, t, H, & W~ILCH, C E High-Output Respiratory Fadure A n Important Cause of Death Ascribed to, Pentonms or Ileus Ann. Surg 158 581 ( 1963 )