The physiologic basis of cardiac arrest during anesthesia

The

Physiologic Basis of Cardiac During Anesthesia

Arrest

R. W. PORTER, M.D., PH.D. ANDJ. D. FRENCH, M.D., Los Angeles, California From tbe Surgical Service, Veterans Administration Hospital, Long Beach, Calijornia; and tbe Departments of Anatomy and Surgery, University of California School of Medicine, Los Angeles, Calijornia. Tbis study was supported by a grant from tbe National Institute of Mental Healtb (M-2482).

which serve to mediate viscera1 refIex activity, for exampIe, are Iocated within the R. F. and form an integra1 part of it. The evidence is cIear now which indicates that the R. F. serves to mediate, contro1 and quantify these visceral reffexes and to keep them in proper baIance for maintaining the organism in its environment. This baIance is disturbed, therefore, when anesthetics are administered and the anesthesioIogist records innumerabIe changes in retIex activity as a patient passes through the various stages of induced depression. Changes in cardiac reflex activity are particuIarIy characteristic of drug-induced depression of the R. F. The somatic stimuIus of a premature surgica1 incision, for exampIe, may produce a profound aIteration in the heart beat. Cardiac function, however, is even more sensitive to stimuIi of viscera1 origin, particuIarIy those appIied to organs innervated by the vagus nerve. It is smaI1 wonder then that aIterations in puIse ensue upon such vaga1 stimuIation as that induced in the inadequateIy anesthetized patient by trachia1 intubation, cardiac manipuIation or mesenteric traction. The present investigation was designed to study this phenomenon by attempting an assessment of cardiac reffex excitabiIity as affected by the induction and abatement of deep anesthesia.

occasion, it is usefu1 to review for specialists skiIIed in one discipIine the resuIts of experiments empIoying the tooIs of quite another branch of scientific endeavor when these experiments bear on a topic of common dedication. For this reason, the data reIating to the probIem of cardiac arrest during anesthesia emanating from the neurophysioIogy Iaboratory are presented in the anticipation that they wiI1 be of interest to a forum of surgeons. During the past decade, the core of grey and white matter, occupying the centra1 portion of the brain stem and Iying mesia1 to the Iong tracts which conduct primary sensorimotor information to and from the brain, has been found to be essentia1 to consciousness [3], for destruction of this neura1 mass, caIIed the reticuIar formation (hereafter designated R. F.), resuIts in coma [4]. It can be demonstrated easiIy that this neuraI structure is defunctionaIized reversibIy and seIectiveIy by soporific drugs, since the administration of such agents does not interfere with impuIses recorded in the IateraIIy situated primary tracts whiIe it obIiterates compIeteIy responses travelIing in the R. F. [5]. Th us, agents administered to a patient to render him stuperous and insensitive to surgica1 pain have an afinity for the R. F. and induce the anesthetic state by exerting a specific depressing action upon it. In acting upon the centra1 brain stem core, however, anesthetic agents modify other functions subserved by this region, as it has many in addition to maintaining the conscious, aIert state. The nucIear masses and connections

0

N

American

Journal

of Surgery,

Volume

zoo, August

1960

EXPERIMENTAL PROCEDURE Experiments were performed on nineteen cats and five monkeys anesthetized with either sodium PentothaI@ or ether. One vagus nerve was isoIated and divided, and stimuIating eIectrodes pIaced on its proxima1 end. The other vagus and the sympathetic nerves were Ieft intact. Changes in the eIectrocardiogram resuIted from electrica stimuIation (repetitive negative puIses; I to 3 voIts, 0.1 msec. duration, 50 to IOOpuIses per second; train duration 354

Cardiac

Arrest

During

Anesthesia

ANES.

LEVEL

A. CONTROL

B. LIGHT

@t

MODERATE c’

&+h

D. DEEP

--

t stim FIG. 2. Diagrammatic representation of reticular formation response to sciatic nerve stimuIation under various IeveIs of anesthesia. Cardiac irreguIarities couId be induced by vaga1 stimuIation only during (C) when long Iatency evoked response was fuIIy manifest. FIG. I. Diagram indicating the experimenta design used in these studies. ReticuIar formation (cross hatched) excitabiIity under various stages of anest‘hesia was determined by recording its electrical response to sciatic nerve stimulation. This was correIated with status of visceral refIexes as determined by cardiac response to stimuIation of proxima1 end of cut vagus nerve.

it disappeared soon after the administration of the agent was begun. (Fig. 2B.) When anesthesia was sIowIy induced, or given in divided doses in the case of barbiturates, a second evoked response was often encountered which was never seen in the waking state. This response was seen at a moderate depth of anesthesia and occurred some 40 to 80 msec. after stimuIation of the sciatic nerve. (Fig. 2C.) This Ionger Iatency response eventuaIIy disappeared with very deep anesthesia (Fig. 2D) but potentiaIs couId stiI1 be recorded from the more IateraIIy situated Iong sensory tracts from stimuIation of the sciatic nerve. As the anesthetic state became dissipated the responses reappeared in the reverse order, that of Iong Iatency first and of short latency upon resumption of consciousness [2]. The cardiac rate was reIativeIy IittIe influenced by vaga1 stimuIation, aside from modest sIowing, during a11 stages of anesthesia except one. The Iong latency response, upon reaching maxima1 ampIitude in the R. F., however, signaIed a degree of reticuIar hyperexcitabiIity which presaged the deveIopment of cardiac irreguIarity incIuding compIete standstiI1 in response to stimuIation of the vagus nerve. The decIine and disappearance of this

of 5 to IO seconds) of this nerve at various levels of anesthesia. The status of this and other viscera1 reflexes was correIated with the functiona integrity of the brain stem R. F. The excitabiIity of the R. F. was determined by measuring the characteristics of the eIectrica1 potentiaIs evoked within it from stimuIation of the sciatic nerve (singIe negative threshoId puIse; 2 to 3 voIts; o. I msec. duration). (Fig. I .) RESULTS

Confirming previous studies, it was found that R. F. excitabiIity, as determined by potentiaIs recorded from an eIectrode pIaced within it, was strongIy influenced by anesthesia [5]. During the control period, the evoked responses exhibited high ampIitude and occurred about 20 msec. after the stimuIus was appIied to the sciatic nerve. (Fig. 2A.) This response was very sensitive to anesthesia and 355

Porter

and

same Iong Iatency potentia1, either as the resuIt of the administration of more anesthetic or of the withdrawa of the agent, was attended with the reappearance of cardiac reflex stabiIity. These phases of R. F. excitabiIity, characterized by transient sequentia1 appearance of the short Iatency and long latency responses, were easiest to recognize when barbiturates were utiIized due to the greater ease with which the different stages of anesthesia couId be sIowIy deveIoped and sustained.

French great many cases, are: (I) stimuIi appIied during (2) a stage of distorted reticular formation. Thus, a11 conditions which can distort R. F. function appropriately, either singly or by summation, wiI1 predispose a subject to cardioviscera1 instabiIity. Hypoxia, for exampie, hypoglycemia or hypercapnia, when tested neurophysioIogicaIIy, a11 produce depression of the R. F. in a manner simiIar to that resuIting from the administration of anesthesia [r]. These factors, therefore, summating with the many drugs administered before and during operation, may render the R. F. unusuaIIy vuInerabIe and the assessment of its excitabiIity tremendousIy eIusive.

COMMENTS

In these anima1 experiments, cardiac arrest cIearIy was the resuIt of a striking increase in the excitabiIity of the cardiac reflex which occurred at a specific depth of anesthesia. This reflex hyperexcitabiIity in turn correIated preciseIy with a change in reactivity of the R. F., signaIed by the appearance within it of a Iong Iatency evoked response. It may be that the reffex hyperpresumed, therefore, excitabiIity Ieading to cardiac arrest was centra1 in origin and indicated a drug-induced distortion of visceral rehex contro1 normaIIy mediated by the R. F. If these experiments can be extrapoIated to man, it shouId be concIuded that, at a stage of anesthesia, defined by the appearance of the long Iatency response in the R. F., the patient should be vigorousIy protected from al1 sensory stimulation particularly that applied to the vaga1 system. Since the surgeon and anesthesioIogist wi11 not be abIe to monitor an eIectrode in the R. F. of patients at operation, however, it wiI1 be necessary to detect the stage of reticular hyperexcitability by some other means not yet avaiIabIe. In animaIs, the period of hazard from cardiac arrest occurred when the pupi was constricted, the Iight reflex was still present and the carotid sinus reflex was enhanced. HopefuIIy it wiI1 be possibIe to contro1 such viscera1 hyperexcitability by the administration of drugs which might depress reticuIar activity directIy or its motor output through periphera1 autonomic pathways. The matter appears to be susceptible to further cIinica1 and experimenta definition, however, and such investigations shouId be pursued vigorousIy in the interests of precision and safety. CIinicaI cardiac arrest has been ascribed to a myriad of causes and there can be no doubt that many exist. However, it is very IikeIy that the basic mechanisms invoIved, at Ieast in a

REFERENCES

I. ARDUINI, A., and ARDUINI, M. G. Effect of drugs and metaboIic aIterations on brain stem arousa1 mechanism. J. Pbarmacol. H Exper. Tberap., IO: 76

1954.

2. FELDMAN, S. and PORTER, R. W. Long Iatency responses evoked in the anterior brain stem under deep pentobarbita1 anesthesia. Electroencepbalog. ti Clin. Neuropbysiol., 12: II I, rg6o. 3. FRENCH, J. D. The reticuIar formation. J. Neurosurg., 15: 97. Ig#. 4. FRENCH, J. D., VON AMERONGEN,F. K. and MAGOUN, II. W. An activating system in brain stem of monkey. Arch. Neurol. w Psycbiat., 68: 577, 1952. 5. FRENCH, J. D. and KING, E. E. Mechanisms invoIved in the anesthetic state. Surgery, 38: 228, ‘955. DISCUSSION

CaIif.) : The authors are to be congratuIated for their very stimutating and thought-provoking presentation of a subject which rests heaviIy upon the shouIders of every surgeon. I should Iike to teII you briefly of Dr. French’s background. He is quaI%ed as a genera1 surgeon as we11 as a neuroIogic surgeon, and whiIe he has devoted much time to cIinica1 surgery, his deep devotion has been to the research Iaboratory from which he has made many vaIuabIe contributions to the fieId of neurophysioIogy. With Dr. H. W. Magoun of U.C.L.A. MedicaI SchooI, Dr. French has organized a vast neurologic research Iaboratory at the Long Beach Veterans HospitaI, encompassing more than IOO students working on various phases of neurorogic probIems. This is the Iargest Iaboratory of this type in the worId. PresentIy, he is professor of anatomy and cIinicaI professor of surgery at U.C.L.A. Medical SchooI. He is aIso director of the new Brain Research Institute which is being organized at U.C.L.A. HOWARD A. BROWN (San Francisco,

356

Cardiac

Arrest During

Anesthesia

greater attention be given to the patient’s preoperative condition and stressed the need for carefu1 attention to induction of anesthesia, adequate airways and oxygen exchange, and drug dosage and other possibIe contributing factors. The authors’ concepts undoubtedIy wiI1 add materiaIIy to a better understanding of this critica problem in the future. I am hopeful that further study, both from the standpoint of anesthesia and the neurophysioIogic impact it has on the nervous system, will eventually give us a more definitive answer to the etioiogic factors involved, and thereby Iighten the Ioad on the shoulders of a11 surgeons. WILLIAN P. MIKKELSEN (Los Angeles, Calif.): In the paper presented here five years ago by Dr. Berne and me, we beIieved that IittIe evidence existed to indict vaga1 effect in the genesis of cardiac arrest. The present paper naturally has stimuIated our interest. The question I wish to ask is whether the vaga1 stimuIation used in these experiments was proIonged or short. If the stimuIus was but a short burst, did the induced cardiac arrest persist after discontinuation of the vaga1 stimuIus? If this Latter situation was obtained, the authors’ presentation is of great significance. If it does not, the significance is open to question. J. D. FRENCH (cIosing): To answer Dr. Mikkelsen, a train of stimuIi were applied to the vagus nerve, but a short burst rather than a continuing train. Sometimes when this train was terminated the heart did not start again.

I do not know how many of you are members of the “Cardiac Arrest CIub” but I assure those who do not beIong that it is a most distressing and frightening experience. I had the misfortune to have two patients with arrests in the past thirty years, both occurring within a period of ten days in the x-ray department whiIe spina air studies were being made under sodium PentothaI anesthesia. Cardiac massage was undertaken in both, one patient recovering compIeteIy, the other surviving for twenty-four hours. FortunateIy, the Iatter was a patient with severe mental deterioration who had a hopeIess prognosis. Drs. Porter and French have pointed out new and interesting physiologic observations in the reticular formation in various stages of anesthesia, indicating that minima1 stimuIi of various types may precipitate cardiac arrest. It becomes even more apparent then that the surgica1 procedure itself is not the major consideration but the condition of the patient with reference to his anesthesia and the physioIogic changes that this produces are probabIy the critica factors in cardiac arrest. This subject was exceIIentIy presented by our President (Dr. Berne) and his associates at this meeting in 1955. Most of us were amazed at the apparent increasing frequency of this condition. Dr. Berne reported one cardiac arrest in every 585 surgical procedures at the Los AngeIes County HospitaI and a recovery rate of onIy seventeen cases of fifty-seven in which resuscitation was attempted. He aIso pointed out the physiologic changes occurring under anesthesia, urged that

357