Brit. J. Anaesth. (1968), 40, 583

THE EFFECT OF GENERAL ANAESTHETIC AGENTS ON NERVECONDUCTION VELOCITIES

BY

J. A. THORNTON, D. WHELPTON AND B. H. BROWN

SUMMARY

Nerve conduction velocity has been studied in the ulnar nerve of human subjectsbefore and during anaesthesia. No significant changes in velocity were observed follow-ing the administration of thiopentone, nitrous oxide, oxygen and halothane in normalclinical quantities. A transient increase in nerve conduction velocity was noted followingthe administration of paralytic doses of gallamine triethiodide to subjects receivingnitrous oxide, oxygen and halothane anaesthesia in whom ventilation was controlled.

Using modern techniques and equipment themeasurement of both sensory and motor nerveconduction velocities is possible and often useful(Dawson, 1956; Gilliatt et al., 1965; de Jong,Hershey and Wagman, 1966; de Jong and Nace,1967).

During investigations into the degree of dam-age to the central nervous system present inchildren born with spina bifida it was necessaryto make conduction velocity measurements dur-ing surgical operations (Brown, Porter and Whit-taker, 1968). The question was soon raised as towhat effect, if any, the anaesthetic agents beingused might have on the conduction velocitymeasurements being made. There appeared to belittle information in the literature on this subject,although some sources stated that large doses ofcertain anaesthetic agents in vitro reduced nerveconduction velocities (Wyke, 1965). de Jong,Hershey and Wagman (1966) report that halo-thane in inspired concentrations up to 2.5 percent has an insignificant effect on motor nerveconduction velocity at temperatures between 35°and 36 °C, in man and cat. This lack of effecthas been subsequently confirmed for ether,methoxyflurane, halothane, and nitrous oxide inthe cat (de Jong and Nace, 1967).

It was therefore decided to make a series ofnerve conduction velocity measurements onpatients during operations not involving thenerves on which measurements were to be made.

METHOD

The nerve chosen for study was the ulnar nerve.As this nerve runs superficially in certain parts

of its course in the human subject, measurementscould be made using surface electrodes ratherthan needle electrodes. The method used wassimilar to that first used by Dawson (1956), andconsisted of giving a short electrical stimulus tothe nerve at the wrist and then detecting thecombined orthodromic sensory, and antidromicmotor impulses at the elbow joint. The voltagedetected was displayed on a storage oscilloscopefrom which a polaroid photograph could be takenif necessary (fig. 1). Only one measurement wasmade from each photograph, this being theinterval of time between the electrical stimulusand the peak of the signal detected over the nerveat the level of the elbow. Measurement of thedistance between the stimulating cathode and the

FIG. 1Typical action potential recorded over ulnar nerve atwrist following stimulation of ulnar nerve at elbow.

First deflection represents stimulus.

584 BRITISH JOURNAL OF ANAESTHESIA

detecting electrodes enabled a conduction velocityto be determined.

To establish a baseline conduction velocity foreach patient, a reading was first made on the daypreceding operation and then in the anaestheticroom just before induction of general anaesthesia.Measurements were then made at 10-minuteintervals after induction for as long a period aspossible. It did not prove practicable to leave theelectrodes in position on the patient from the daypreceding operation. However, the electrodesattached in the anaesthetic room were not re-moved whilst the patient was taken into theoperating theatre. This eliminated a possible errorin measurement due to inconsistent electrodeplacement. Skin temperature was measured con-tinuously at the site of application of the elec-trodes using a thermistor.

Measurements were made in a total series of43 male and female patients. In all the casespremedication consisted of the intramuscularinjection of morphine 10 mg and atropine 0.6 mg1 hour pre-operatively. Induction of anaesthesiawas carried out using 2.5 per cent thiopentone,with maintenance by 70 per cent nitrous oxideand 30 per cent oxygen with 0.5—1.5 per cent halo-thane. In addition a number of patients receivedparalyzing doses of gallamine tnethiodide inorder to achieve full muscular relaxation for intra-abdominal surgery. In a smaller series sub-paralytic doses of gallamine triethiodide (40 mg)were used in conjunction with nitrous oxideoxygen and halothane; short periods of spon-taneous ventilation were permitted in these cases.The patients receiving paralyzing doses of galla-mine (120 mg) were all intubated using a cuffedorotracheal tube.

For the purpose of analysis the results weredivided into four groups:

A Patients in whom gallamine was not used.

B Patients in whom gallamine 40 mg was usedand spontaneous respiration permitted.

C Patients in whom paralyzing doses of gal-lamine was used and ventilation controlled.

D 11 further cases (7 females and 4 males) re-ceiving thiopentone, nitrous oxide, oxygenand halothane, gallamine 120 mg and con-trolled ventilation were then studied ingreater detail as Groups B and C appeared to

show time dependence conduction velocitychanges. All the cases received similar pre-medication. Induction and maintenance wascarried out with thiopentone, nitrous oxide,oxygen and halothane together with gal-lamine 120 mg. Conduction velocity wasmeasured, where possible, immediately be-fore injection of gallamine, and at 5, 10, 15,20 and 30 minutes following paralysis andinitiation of controlled ventilation.

Any changes in conduction velocity were ex-pressed as a percentage change from pre-inductionmeasurements.

RESULTS

The pre-operative mean conduction velocity in32 patients was 58.0 m/sec. In Group A (6patients receiving thiopentone, nitrous oxide,oxygen and halothane) the mean percentagechange between pre-operative readings and theobservations taken at 10-minute intervals afterinduction was —0.40 per cent (n=13, P=0.8).This change is not significant.

In Group B (6 patients receiving thiopentone,nitrous oxide, oxygen, halothane and gallamine40 mg, breathing being spontaneous). The meanpercentage change between pre-operative read-ings and the observations taken at 10-minuteintervals after induction was +0.78 per cent (SEof mean 0.78 per cent, n=13 , P = 0 3 ) . Thischange is not significant.

In Group C (11 patients receiving thiopentone,nitrous oxide, oxygen, halothane and gallamine120 mg, ventilation being controlled) the meanpercentage change between pre-operative read-ings and the observations taken at intervals of10 minutes after induction was +2.33 per cent(SE of mean 0.56 per cent, n=35 , P<0.001).This change is significant.

In Group D (11 further cases, 7 females and4 males, receiving thiopentone, nitrous oxide,oxygen, halothane and gallamine 120 mg, ventila-tion being controlled), which were studied ingreater detail because Groups B and C appearedto show time dependence of conduction velocitychanges, the results (fig. 2) showed an overallincrease in the mean conduction velocity, follow-ing the intravenous injection of gallamine of1.7 per cent (SE of mean 0.39 per cent, n=40,P<0.001). This change is significant.

GENERAL ANAESTHETIC AGENTS AND NERVE CONDUCTION 585

3-

2-O

IO 15 2O 25 3O

N=4

TIME IN MINUTES

FIG. 2

Mean changes in conduction velocity (as per cent ofcontrol) in 11 patients. Anaesthesia consisted of thio-pentone, nitrous oxide, oxygen, halothane, and gal-lamine 120 mg. Ventilation was controlled. The

standard error of the mean values is shown.

These observations confirmed the previous sug-gestion arising from the results from Groups Band C that there was a relationship between thepercentage change and die time after the adminis-tration of gallamine.

Minutes05

10152030

2x0

13.128.916.77.80.6

n09

11974

x%0

+ 1.46+ 2.63+ 1.86+ 1.11+ 0.15

SEN

0.620.650.830.570.25

When die values for Groups C and D are com-pared widi those for Group A (gallamine 120 mgagainst cases who received no gallamine), diedifference was significant for bodi C and D (GroupC, P<0.05; Group D, P=0.06). Due to thescatter of die cases in Group A the significance isnot as great as one would expect.

There was a statistically significant increase innerve conduction velocity following the intra-venous administration of gallamine, with a returnto normal velocities at approximately 25-35 min-utes after injection. There was no significantchange in nerve conduction velocity in patientsreceiving thiopentone, nitrous oxide, oxygen andhalodiane, and breadiing spontaneously.

DISCUSSION

A number of possible explanations for the timedependence of the nerve conduction velocity fol-lowing die administration of gallamine.

Temperature change, de Jong, Hershey andWagman (1966) showed that nerve conductionvelocity decreases linearly widi temperature. Inthe case of the peroneal nerve of die human sub-ject this decrease was of tie order of 1.84m/sec/°C between 36° and 23°C. The observedresults in the present series could therefore beexplained by an increase of body temperature ofapproximately 1°C. Observations of skin tem-perature did not show such increases. Transientincrease in the temperature of blood perfusingdie nerve could account for diis change, butduring anaesdiesia widi nitrous oxide, oxygen andhalothane only this effect was not demonstrated,and to account for it gallamine must have pro-perties ascribed to it which have not heretoforebeen attributed to it. Temperature change is

586 BRITISH JOURNAL OF ANAESTHESIA

therefore an unlikely explanation of this pheno-menon.

Carbon dioxide. Alkalaemia is known to in-crease the excitability of nervous tissue (Wyke,1965) and may well give rise to an increase innerve conduction velocity. Such an alkalaemia islikely to develop following controlled ventilationas a result of respiratory alkalosis. It has beenshown (Robinson, 1961) that such an alkalaemiamay take up to 1 hour to develop as a result ofpassive hyperventilation, and therefore is unlikelyto be the explanation for the initial rise in con-duction velocity found to occur following theadministration of gallamine. Furthermore, thedevelopment of alkalaemia is likely to be sustainedlonger than the observed change in nerve con-duction velocity which returns towards the base-line about 10 minutes after the administration ofgallamine.

Similarly a change in the level of carbondioxide tension and stores follows the same pat-tern as the development of alkalaemia with theattainment of a new level of carbon dioxidetension, the 95 per cent change occurring in about20 minutes follows the change of ventilation.Carbon dioxide tension is likely to rise after theadministration of gallamine 40 mg and spon-taneous ventilation, though no change in nerveconduction velocity was noted in these cases.Change in carbon dioxide tension is thereforeitself unlikely to account for the observed patternof change in the nerve conduction velocity follow-ing the administration of gallamine. Rate ofchange of carbon dioxide and pH might, however,account for this observed phenomenon, and insome way influence ionic transfer in nerve tissue.

The effect of gallamine. The close correlationbetween the return to normal values of the nerveconduction velocity after the administration ofgallamine, and the known duration of clinicaleffect, suggest that the increase in nerve conduc-tion velocity could be direcdy attributed to theaction of gallamine. The fact that small doses ofgallamine did not produce any marked change innerve conduction velocity suggests that amount ofgallamine may be a factor in producing thesechanges. There is evidence to suggest a centralexcitatory action of gallamine on the nerve system(Halpern and Black, 1967). The observed effectscould, however, in some way be a function of

neuromuscular blockade and may not be specificto the use of gallamine.

Further studies using other neuromuscularblocking agents are in progress, and investigationsinto the possible effects of carbon dioxide arebeing continued. In the meantime, although theobserved changes are admittedly small, work todate suggests that caution should be employed inevaluating nerve conduction velocities from onesingle observation and, in addition, regard shouldbe paid to the possible effects of neuromuscularblocking agents.

ACKNOWLEDGEMENTS

The authors wish to acknowledge the help andco-operation of Professor C S. Russell and ProfessorH. L. Duthie without which this study would not havebeen possible and for the technical assistance ofMessrs. A. Robinson and D. Wortley.

REFERENCES

Brown, B. H., Porter, R. W., and Whittaker, G. (1968).Nerve conduction measurements in spina bifidacystic. J. Devel. Med. Child. Urol, SuppL 15, 78.

Dawson, G. D. (1956). The relative excitability andconduction velocity of sensory and motor nervesin man. J. Physiol. (Lond.), 131, 436.

GiUiatt, R. W., Melville, I. D., Vclate, A. S., andWillison, R. G. (1965). A study of normal nerveaction potentials using an averaging technique(barrier grid storage tube). J. Neurol., Neurosurg.Psychiat., 28, 191.

Halpern, L. M-, and Black, R. G. (1967). Flaxedil(gallamine triethiodide): evidence for a centralaction. Science, 155, 1685.

de Jong, R. H., Hershey, W. N., and Wagrnan, I. H.(1966). Nerve conduction velocity during hypo-thermia in man. Anesthesiology, 11, 805.Nace, R. A. (1967). Nerve impulse conduction

and cutaneous reciptor responses during generalanesthesia. Anesthesiology, 28, 851.

Robinson, J. S. (1961). Some biochemical effects ofpassive hyperventilation. Brit. J. Anaesth., 33, 69.

Wyke, B. D. (1965). Neurological principles in anaes-thesia; in General Anaesthesia (eds. Evans, F.T.,and Gray, T. C). London: Butterworth.

L'EFFET D'ANESTHESIQUES GENERAUXSUR LA VITESSE DE CONDUCTION

NERVEUSE

SOMMAIRE

La vitesse de conduction nerveuse a tti 6tudi& aunerf ulnaire de sujets humains avant et durant 1'anes-tWsie. Aucune modification significative de la vitessen'a M observed apres radministration de thiopentone,protoxyde d'azote, oxygene et halothane en quanritescliniques normales. Mais une augmentation passagerede la vitesse de conduction nerveuse a £t£ remarqueeapres radministration de doses paralysantes dutriethiodure de gallamine a des sujets, recevant uneanesthesie de protoxyde d'azote, oxygene et halothanesous respiration assistee.

GENERAL ANAESTHETIC AGENTS AND NERVE CONDUCTION 587

DER EINFLUSS VON ALLGEMEIN-NARKOTIKA» AUF DIE NERVENLEITUNGS-

GESCHWINDIGKEIT

ZDSAMMENFASSUNG

Bei Versuchspersonen wurdc am Nervus ulnaris vorund wahrend der Narkose die Nervenleitungsgesch-windigkeit untersucht. Im AnschluB an die Vcra-

breichung von Thiopentan, Lachgas, Sauerstoff undHalothan in nonnalen klinischen Quanutaten wurdenkeine signifjkanten Geschwindigkeitsanderungen beo-bachtet. Fine yorubergehende Zunahme der Nerven-leitungsgeschwindigkeiten wurde jedoch festgestellt,wenn Personen, die cine Narkose mit Lachgas,Sauerstoff und Halothan bei kontrollierter Beatmungerhielten, paralytische Dosen Gallarnintriethiodid(Flaxedil) verabreicht wurden.

BOOK REVIEW

Anaesthesia and Resuscitation: a manual for medicalstudents. Edited by R. A. Gordon. Published byUniversity of Toronto Press. Pp. 179 + ix; illus.;indexed. Price 24s.

This 179-page paperback is written by fourteenCanadian anaesthetists—most of whom are well known—under the editorship of the Editor of the CanadianAnaesthetists' Society Journal. We are not told thewriters of individual chapters, which vary somewhatin their standard and which overlap occasionally. Theopening challenging preface puts the subject in trueperspective for students. Its fifteen chapters deal withall the aspects of anaesthesia with which a medicalstudent and newly qualified doctor should be familiarOne might disagree with the topics on which specialemphasis has been placed, but such criticism musttake into consideration the requirements of the doctorsin the country for which the book is intended.

Starting towards the end of the book, the chapter(12) on complications of anaesthesia deserves specialmention and is worth reading by doctors of all grades.It certainly emphasizes the seriousness with whichbeginners should approach the administration of ananaesthetic. On a par with this is the section on"Cardiovascular homeostasis in relation to anaesthesiaand resuscitation" (Chapter 9). The introduction tothis is excellent; in a very brief space the physiologyof the whole topic is very clearly explained, with lotsof good clear definitions. It is regrettably spoiled by asweeping statement (page 86) that "the safety of anyindividual anaesthetic depends more on the skill withwhich it is administered . . . than on any inherentproperty of the drug". While agreeing that this ispartially true, one has to ask how ethyl chloride andchloroform fit into this generalization. (Perhaps thesedrugs should not be used by students, but they arediscussed on pages 32 and 33.) Should a warning notbe given as to their cardiovascular toxicity?

Virtually every sentence of the short opening seven-page chapter on "Evaluation of the patient" is a fountof information, but the four references at the end seemquite irrelevant and a fuller bibliography would helphere. One would like more detailed explanation ofsome aspects of the topic (such as in renal disease orporphyria) rather than short dogmatic statements.Probably the right approach for educated persons is togive more relevant background information, althoughthe other might be ideal in a manual for nurse-anaesthetists. While realizing that anaesthesia is onlyone of the many subjects to be covered by the medicalstudent in a short period of time and that a long bookwould be of little use to them, the degree of brevityadopted in this chapter may put the student off. Thisdidactic style is continued in the second short (too

short?) chapter on premedication where there is a lackof clarity in describing the objects of premedicationand the (placsbo) value of a pre-operative visit by theanaesthetist.

Chapter 3, especially page 15, makes certain assump-tions as regards the bask knowledge possessed byreaders, e.g. what controlled respiration is and what itentails or what a cuffed endotracheal tube is. An illus-tration here would have been most helpful.

The longest chapter (4) on general anaesthesia isadequately illustrated with circuits, etc., except for theneed for a simple line drawing of a gas machine onpage 38. An opening definition of what is generalanaesthesia and what is local anaesthesia would havebeen helpfuL This also applies to the terms "neuroleptanaesthesia", "depth of anaesthesia", "hypnotics","sedatives", etc.

On a point of personal interest, the reviewer depre-cates the continued use of the misleading term "ultra-short acting" in relation to intravenous barbiturates,particularly in a work written for students. It is alsoworth correcting the statement (page 35) that "Hexo-barbital was the first barbiturate anaesthetic used". Itcertainly was the first rapidly acting barbiturate, andthis point should be clarified.

There is a clear and simple exposition of the actionof muscle relaxants and the ten pages devoted to thisstrike a good balance in relation to what a studentshould know about these drugs. In contrast, the sixpages devoted to regional anaesthesia, however, seemtotally inadequate, even for students, particularly sinceonly half a page is devoted to nerve blocks.

Obstructed respiration is still probably the mostimportant aspect of the handling of the unconsciouspatient, as far as the beginner anaesthetist is con-cerned, and deserved more space than that devoted toit in Chapter 7, although this is discussed fully else-where (Chapter 12). Finding table I in Chapter 7caused the reviewer some trouble until it was realizedthat the tables and figures in each chapter werenumbered separately. One wonders whether this usefulchapter should not have come immediately after thaton respiration.

The book ends with a challenging section on thespecial problems associated with paediatric anaesthesiawhich should stimulate some to consider that anaes-thesia is a worthwhile subject for specialization.

Despite any criticisms made in this review, and theoccasional printing error, this is still a most helpfulbook. Its greatest use in this country would appear tobe for those intending to spend a year or so inCanada or to join the "brain drain". It pioneers a newidea of paperback anaesthetic books for students,which is quite commendable.

John W. Dundee