ANNALS OF SURGERYVol. 143 FEBRUTARY, 1956 No. 2

Induced Hypotension for Neurosurgical Procedures:A Critical Analysis'

C. R. STEPHEN, M.D. BARNES WOODHALL, M.D., GuY L. ODOM, M.D.,D. REYNOLDS, M.D., M. BOURGEOIS-GAVARDIN, M.D., R.C. MARTIN, M.D.,

AND B. M. BLOOR, M.D.Durham, N. C.

From the Divisions of Anesthesia and Neurosurgery, Duke University Hospital and School of Medicine,Durham, North Carolina

THE PURPOSEFUL production of hypoten-sion during surgical operations by means ofganglionic-blocking drugs was describedclinically for the first time in 1950.7 In theensuing interval, a preliminary wave ofoptimism3' 4 has been supplanted to someextent by a desire for more careful appraisalof this technic.2' 10 Surgeons and anesthe-siologists appear united in the belief thatthe end-result to be attained, i.e., decreasedbleeding at the operative site, is a desirableachievement. However, concern has devel-oped over the relative lack of knowledgerelating to the effects which profound orprolonged hypotension may have on thevital organs of the body. Before this methodis adopted in any particular patient, onemust be certain that the modus operandi isnot more hazardous than would be the op-eration under normotensive circumstances.

Clinical and laboratory investigationsduring and after induced hypotension arenot numerous, particularly in patients un-dergoing operative procedures. One studyconducted in unanesthetized patients indi-cates that there is "little danger of cerebralor renal anoxia in the supine patient with amean blood pressure as low as 55 mm. Hg

* Supported in part by a grant from CibaPharmaceutical Products, Inc., Summit, New Jersey.

Submitted for publication May, 1955.

when employing hexamethonium."'l Similarfindings pertaining to cerebral oxygenationhave been obtained with another gangli-onic-blocking drug, Pendiomide.12 Datafrom animals reveal a slight decrease inrenal blood flow during induced hypoten-sion.13 Bromage5 describes a "cyanotic" liverin patients under epidural anesthesia atsystolic pressures between 45 and 60 mm.Hg, and infers th-at liver damage may resultfrom such temporary hypoxia resultingfrom hypotension. The same author" reportson the electroencephalographic evidence ofischemic cerebral anoxia in three unanesthe-tized patients subjected to induced hypo-tension with pentamethonium iodide. Aprolonged alteration of cerebral electro-activity was noted in a hypertensive arte-riosclerotic patient. Recent animal workrelating to liver function and hypotensionconducted in this institution' shows that asystolic pressure of 30 mm. Hg induced bychemical ganglionic blockade is less damag-ing than when a similar reduction in pres-sure is produced by hemorrhage. However,when a systolic pressure of 30 mm. Hg isprolonged from 30 to 45 minutes by suchdrugs as Arfonad,® the degree of liver dam-age increases significantly, and the mor-tality rate of the animals increases from 10per cent to 36 per cent.

143

STEPHEN et al.

TABLE I. A. Age of Patients.

Less than 21 .............................. 3 5.0%c21 to 30 ................................. I 1 18.6%31 to 40 ................................. 16 27.1%41toS0 ................................. 19 32.2%Over 50 ................................. 10 17.0%

B. Sex of Patients.Male .27Female .32

TABLE II. Surgical Diagnosis.

Cerebral Aneurysm .24Meningioma .12Arteriovenous Anomaly.10Glioblastoma Multiforme. 6Astrocytoma, Undifferentiated. 2Miscellaneous .S

It is the aim of this report to list certainobservations associated with hypotensioninduced under anesthesia during neurosur-

gical procedures, with the hope that some

further understanding of the value andhazards of this method may emerge.

Several means of reducing blood pres-

sure during operations have been de-scribed.15 In this series hypotension was

produced by chemical ganglionic blockade.The drugs employed were Pendiomide,* a

diquaternary dibromide, Arfonad,t a thio-phanium derivative, and hexamethoniumbromide. Each of these drugs is believedto act specifically at the ganglionic synapse

and in a competitive manner. In sufficientdosage each will block completely bothsympathetic and parasympathetic impulses,including both efferent and afferent path-ways. The principal effect desired for in-duction of hypotension is interruption ofthe sympathetic efferent impulses, so thata reduction in arteriolar tone occurs. Withthe abolition of peripheral vascular resist-

' Pendiomide was supplied through the cour-

tesy of Ciba Pharmaceutical Products, Summit,New Jersey.

f Arfonad was supplied through the courtesyof Hoffman-La Roche, Ltd.

t Hexamethonium was supplied through thecourtesy of Burroughs Wellcome & Company, Tuck-ahoe, New York.

TABLE III. Efficacy of Drugs Employed to InduceHypotension.

VasopressorDrug Patienits Unsatisfactory Required

C6 ........... 10 4 40% 6 60%Arfonad 14 4 28.5% 7 50%Pendiomide... 39 8 20.5% 11 28.2%

TABLE IV. Mean Arterial Pressure Changes withControlled Hypotension.

Before After

Case Cuff Radial Cuff Radial

E. B ........... 153 120 94 69E. F ........... 127 111 75 49R.H ........... 120 110 79 36E. P ........... 188 145 70 50K. S.. .. 100 72 71 46E. D ........... 90 78 ? 24W. L........... 90 70 ? 10J. P........... 90 74 ? 28H. T ........... 107 80 ? 26Mkl. B ........... 127 135 7 38

Note that arm cuff pressures are higher than those obtainedby direct readings. Cuff pressures unobtainable at low systoliclevels.

ance, a high systolic pressure is no longerrequired for adequate circulation of theblood.9 A reduced systolic pressure, associ-ated with adequate return of venous bloodto the heart, and with proper posturing,results in less bleeding at the operative site.It is established that ganglionic-blockingdrugs wil produce this sequence of eventswith a varying degree of consistency, butopinion is vague concerning what lowerlevel of arterial pressure may be consid-ered "safe," and particularly the length oftime such hypotension can be allowed toexist without irreversible changes in vitaltissues.

METHOD OF STUDY

Fifty-nine neurosurgical patients betweenthe ages of 16 and 75 (Table I) wereinvestigated. With few exceptions, thesepatients were suspected of having vascularanomalies within the brain, or to be suffer-ing from extensive vascular tumors (TableII). In most instances it was the consensusof opinion that adequate dissection andmanipulation would have been most diffli-

144

Aninals of SurgeryFebruary, 1956

Volume 143 INDUCED HYPOTENSION FOR NEUROSURGICAL PROCEDURESNumber 2

TABLE V. Mean Arterial Pressure Changes withControlled Hypotension.

Before After

Case Cuff Radial Cortical Cuff Radial Cortical

W. A. 102 94 94 82 70 52M. B. 104 90 44 54 55 20F. H. 113 99 70 81 99 64K. O. 73 73 55 60 49 41V. R. 86 80 50 60 38 26M. S. 104 85 66 81 60 36L. B. 97 87 20 51 37 4C. Mc. 133 - 100 93 - 62A. R. 114 84 66 ? 68 56B. S. 91 90 80 ? 68 40D. Mc. 129 99 56 ? 45 24G. S. 103 86 79 ? 37 -H. K. 126 84 64 ? 16 12C. T. 145 93 45 ? 21 20M. W. 108 89 83 ? 23 21

Note again that mean arm cuff pressures when obtainableare higher than mean radial arterial pressures. Gradientbetween radial and cortical arterial pressures tends to followconstant pattern. Abnormal cortical readings believed due tosmall size of vessel cannulated.

cult and hazardous without the benefit ofinduced hypotension. Many patients wereconsidered poor operative risks. In 52 pa-tients anesthesia was induced with Pento-thal sodium, Vinethene and ether, and wasmaintained after endotracheal intubationwith nitrous oxide, oxygen, and smallamounts of ether, employing the non-re-breathing or partial rebreathing technic.In seven patients, endotracheal intubationwas performed under pentothal sodium anda muscle relaxant, with subsequent inhala-tion of nitrous oxide, oxygen and trichlor-ethylene by non-rebreathing technic formaintenance. All patients were kept in lightplanes of anesthesia during the operativeprocedures. After the production of hypo-tension, satisfactory anesthesia could bemaintained with minimal concentrations ofdrugs.With anesthesia induced, the radial ar-

tery was cannulated and connected by cop-per tubing to a Sanborn electromanometeror a Statham strain gauge, so that constantreadings of the arterial pressure could berecorded on a DC amplifier-recording sys-tem. These direct readings were comparedwith those obtained by the conventional

TABLE VI. Hypotension 50 mm. Hg Systolic or Less.

Normal Hypotension Time in Re-Patient Pressure Lowest Level Mins. covered

1 130/90 so 10 Yes2 170/110 40/20 10 No3 140/80 40/30 20 No4 140/80 40/30 45 Yes5 120/80 20/ ? 5 No6 130/80 40/20 10 Yes7 220/100 40/20 20 Yes8 130/60 40/20 10 Yes9 110/80 40/30 15 Yes10 110/60 50/ ? 10 No11 110/80 40/20 10 No12 100/60 44/ ? 10 Yes13 124/90 45/30 15 Yes14 120/80 48/30 10 Yes15 200/130 40/20 10 No

16 130/80 52/40 10 Yes17 170/110 50/30 45 No

18 130/90 52/40 10 Yes19 160/110 35/25 10 No20 140/80 38/10 5 Yes21 124/80 30/20 10 Yes22 170/110 50/30 30 No23 130/110 20/0 5 Yes24 170/100 40/20 5 No25 138/80 40/20 15 Yes26 150/100 40/30 15 Yes

Tycos sphygmomanometer. After exposureof the brain, and before the induction of hy-potension, direct arterial pressure readingswere taken from one of the superficial cor-tical vessels by inserting a number 27 gaugeneedle into it. This procedure was repeatedafter the arterial pressure was reduced.As indicated above, hypotension in these

patients usually was not induced until afterthe brain cortex had been exposed. Priorto injection of the ganglionic-blocking drug,the patient was placed in a 10 to 20 degreereverse Trendelenburg position. This wasdone to lessen the tendency to venous ooz-ing. If arterial pressure fell too precipitately,improvement in the situation occurred fre-quently with leveling of the table. Thismaneuver reduced the necessity of usingvasopressor drugs.On a number of patients electrocardio-

grams were taken before and after hypo-tension was induced. Liver function beforeand after operation was analyzed by meansof the bromsulfalein test iii several cases.

145

STEPHEN et al. Annals of SurgeryFebruary, 1956

TABLE VII. Mortality.

Lowest Duration

Age Operation Drug, mg. Pressure Mins. Group Comment

1. 40 Partial resection glioma C6, 28

44 Biopsy metastatic brain tumor53 Partial removal glioblastoma52 Partial resection meningioma

23 Subtotal resection ependymoma

36 Ligation bleeding aneurysm

24 Clip berry aneurysm

47 Evac. Temp. lobe hematomaExc. int. carotid aneurysm

33 Ligation aneurysm

57 Partial resection glioblastoma

34 Resection A-V anomaly It.frontal lobe

12. 28 Rem. meningioma exc. aneu-rysm int. carotid

13. 49 Clip ligation aneurysmal sac

14. 48 Partial resection meningioma

15. 75 Trap ligation aneurysm

16. 50 Clip ligation aneurysm

17. 59 Clip ligation aneurysm

18. 56 Arteriovenous anomaly of skull.Cortical atrophy

19. 50 Partial resection meningioma

20. 37 Clip ligation aneurysm

Arfonad, 15Pend., 175Pend., 1200

Pend., 125

Pend., 500

C6, 25

Peind., 500

C6, 50

C6, 25

Arfonad. 470

Arfonad, 200

2.3.4.

5.

6 .

7 .

8.

9.

10.

11.

52/40 10 1 Uneventful recovery. Died 2 monthsP. o.

60/50 5 1 Died 3 months p. o.80/60 15 1 Good recovery. Died 8 months p. o.

90/70 15 1 Fair recovery. Died 24 days p. o.from pul. embolus.

78/68 10 1 Uneventful recovery. Died lhmonths p. o.

80/70 15 2 Died 12 hours p. o. Moribund whenbrought to 0. R. Very poor risk.

70/50 10 2 Died 48 hours p. o. Acute subarach-noid hge. preop. Never recovered.Hypotension not primarily respon-sible.

40/20 10 2 Died 16 hours p. o. Moribund anddecerebrate preop. Very poor risk.

40/30 20 3 Died 48 hours p. o. Did not reactp. o. Cerebral edema.

35/25 10 3 Died 36 hours p. o. Failed to respond.Necrosis midbrain and pons.

20/? 5 3 Hydrocephalus and semiconsciouspreop. Persistent hydrocephalusp. o. Died 3 months p. o.

80/70 20 3 Died 96 hours p. o. Cerebral edema.

Arfonad, t5 50/30 30 3 Died 72 hours p. o. Terminal cardiacfailure (BP. 170/110 preop.) Corti-cal necrosis (?).

Pend., 50 50/? 10 3 Died 48 hours p. o. Never fullyrecovered. Cerebral edema.

Pend., 25 50/30 45 3 Unconscious preop. Never recoveredcompletely. Terminal cardiac fail-ure. Died 96 hours p. o.

Pend., 1500 80/60 10 3 Thrombus It. middle cerebral artery,left hemiparesis. Died 15 days p. o.with secondary rupture aneurysm.

Pend., 30 40/20 5 3 Died 48 hours p. o. Never fullyrecovered.

Arfonad, 80 70/50 30 3 Died 72 hours p. o. Responded for48 hours, then downhill, Thrombo-sis internal carotid artery.

Pend. 125 40/20 10 4 Died 24 hours p. o. Never fully re-covered. Hypothalmic involvement

Pend., 1180 40/20 10 4 Died 28 days p. o. Never responded

COMPARISON OF DRUGS

Hexamethonium bromide was given toten patients intravenously in dosages vary-ing between 25 and 75 mg. Usually 25 mg.was given first, and this supplemented byincrements of 12.5 mg. as indicated. Effec-tive hypotension was produced in nine ofthese patients, lasting from 21 minutes toseveral hours. Six patients required theadministration of a vasopressor, either toreverse an extremely low arterial pressureshortly after the production of hypotension,or to reduce the prolonged effect seen fre-quently with this ganglionic-blocking drug.

In four cases the reduction in bleeding atthe operative site was considered unsatis-factory by the surgeon. Figure 1 is a typicalanesthetic record employing hexametho-nium bromide.Arfonad® was administered on 14 occa-

sions. This drug was given as a continuousor intermittent drip, as described else-where,14 in a concentration of 1 mg. per ml.The dosage range varied between 15 and900 mg. Hypotension produced by thismeans was considered adequate in 12 pa-tients, and lasted from intervals of 20 min-utes to several hours. Seven patients re-

146

INDUCED HYPOTENSION FOR NEUROSURGICAL PROCEDURES

ANESTHESIA RECORDDUKE HOSPITAL

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quired the administration of a vasopressor,in most instances to reverse an extremelylow arterial pressure shortly after the induc-tion of hypotension. In four cases hypoten-sion was considered inadequate by the sur-

geon. Figure 2 is a representative anes-

thetic record when Arfonad was employed.Hypotension was attempted in 39 patients

with Pendiomide. Usually a preliminarydose of 25 to 50 mg. was given intrave-nously, and this was followed either by

fuirther intermittent doses, or by a continu-oUs drip administration of a soltution con-

taining 1 mg. per ml. The continuous dripadministration appeared more satisfactory.The dosage required by patients variedbetween 25 and 1500 mg., and the effectslasted from 40 minutes to several hours.

Noticeable hypotension was produced in

37 of these patients. Eleven patients re-

quired the injection of vasopressors eitherduring or after operation to combat abnor-mally low arterial pressures. In eight pa-tients the surgeon did not feel that the tech-nic controlled bleeding adequately. Figure3 shows the type of anesthetic record ob-tained with Pendiomide. A summary ofthese findings is found in Table III.

It seems that each of the drugs enumer-

ated is capable in some patients of produc-ing a degree of hypotension which dimin-ishes bleeding in a manner which is satis-factory surgically. The predictability ofthis response from one patient to anotheris not encouraging. It is acknowledged thatthe older age group, suffering from arterio-sclerosis, are particularly sensitive to smalldoses of a ganglionic-blocking drug, but

147

Volume 143Number 2

D It1 l /7-52AGE 20

T., H..A.ENAME

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STEPHEN et al.

ANESTHESIA RECORDDUKE HOSPITAL

Annals of SurgeryFebruary, 1956

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that does not explain the wide variation indose requirements seen in other patients, or

the occasional failures noted. Associatedwith this factor is the unpredictable dura-tion of effect noted. Ideally, one would pre-

fer a drug in which a predetermined levelof hypotension could be established andmaintained according to the surgical re-

quirements. Such an ideal has not beenattained in our experience. Table III tendsto indicate that our most satisfactory andsafest results were obtained with Pendio-mide. In support of this it should be ex-

plained that vasopressors were administeredonly when the severity or undue prolonga-tion of the hypotension demanded it.

It may be that the unpredictability ofthe hypotensive compounds, both as to

dosage and duration, is due, not to thedrug itself, but rather to so-called "consti-tutional" variations within the patientsthemselves, or to other forces at work atthe time of administration. The concept thatthe interplay between the parasympatheticand sympathetic systems plays a large partin the internal environment of the patient isgenerally accepted. It may require differentquantities of these drugs to interfere suc-

cessfully with these functions from one

patient to another. With regard to theother forces at work, it should be remem-

bered that drugs which act directly on thearterioles, such as levoarteronal or epineph-rine, will constrict these vessels and reverse

directly the effect produced by ganglionic-blocking compounds. In this series intra-

148

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Volume 143 INDN'umber 2

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NAME Pippin, Ernest

IUCED HYPOTENSION FOR NEUROSURGICAL PROCEDURES

ANESTHESIA RECORDDUKE HOSPITAL

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FIG. 3. D5 8287. Right neck dissection; right fronto-temporal craniotomy with clip ligationBerry aneurysm; temporal fascia dural graft; removal bone flap. Hypotensive drug, pendiomide,210 mg. Satisfactory procedure clinically. Arterial pressure 70/50 for 30 minutes. Convalescenceuneventful, discharged 11 days postoperatively.

venous levoarteronal was most successful inaccomplishing this alteration in emergen-

cies. Under the strain and stress of opera-

tive interference, endogenous epinephrinemay be secreted by the patient to the extentof interfering with arteriolar vasodilatationand preventing adequate hypotension. Onecan hypothesize that such a factor was atwork in the patient represented in Figure 4,where Arfonad, 500 mg., and Pendiomide,1,000 mg., were unsuccessful in reducingblood pressure. On a second occasion tendays later (Fig. 5), the administration ofRegitine, 5 mg., an adrenolytic compound,prior to hexamethonium, 50 mg. intrave-nously, resulted in a satisfactory fall inarterial pressure. The administration ofChlorpromazine, 50 mg., another adreno-

lytic drug, has been of value in three otherpatients.

OBSERVATIONS DURING OPERATION

A. General appearance. After the induc-tion of hypotension, the general appearance

of the patients remained satisfactory. Colorremained good unless hypoxia was super-

imposed inadvertently, and the extremitiesremained warm with palpable pulses unlesscritical blood pressure levels were attained.

B. Arm cuff pressures. A matter of funda-mental importance was the discrepancynoted between blood pressures as recordeddirectly through the radial artery, and thosebased on the conventional arm cuff. As a

rule, those heard with the Tycos manome-

ter were 10 to 20 mm. Hg higher than those149

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ANESTHESIA RECORDDUKE HOSPITAL

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Fic. 4. 1447. Right frontal craniotomy, removal bone flap. Further operation postponedbecause hypotension not obtained with pendiomide, 1000 mg., and Arfonad, 500 mg. Conditionsatisfactory postoperatively.

recorded directly. The larger the patient'sarm, the greater was the variation noted. Asecond factor of significance was the in-ability, in most patients, to hear the bloodpressure through the stethoscope when itfell to 60 mm. Hg systolic or lower. As a

consequence, the direct arterial reading wasnecessary to maintain an accurate guideregarding the cardiovascular system of thepatient. Figure 6 is a pictorial record of thedifferences observed and inadequaciesnoted in one patient. Tables IV and Venumerate some of the patient variationsseen. It is our belief that if this technic ofhypotension is employed, its safety is in-creased considerably by utilizing a directmethod of recording arterial pressure.

C. Respiration. It was rare to find varia-tions in respiratory rhythm associated with

the state of induced hypotension. In threepatients receiving Arfonadg in whom criti-cal systolic pressures of 40 mm. or less werereached, spontaneous respirations ceasedfor an interval of five to seven minutes. Inall other patients the rate and tidal volumeappeared to be changed little even by pro-

found changes in tension. Minimal concen-

trations of anesthetic drugs were require(dto maintain satisfactory conditions duringoperation.

D. Radial and cortical arterial presstures.It was of some interest to determine whatthe relative alterations in cortical arterialpressure were before and after hypotensionwas induced. It should be recalled thatnearly all patients were in a 10° to 20° re-

verse Trendelenburg position at the timethe readings were made. From Table V it

150

". 10/Z/53Gt 3 3IAME C. L. V. -A.)_

Annals of SurgeryFebruary, 1956

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.H A LT-

Volume 143 INDUCED HYPOTENSION FOR NEUROSURGICAL PROCEDURESNumber 2

can be seen that the gradient between ra-dial and cortical pressures remained approx-imately the same before and after the arte-rial pressures fell. It is a matter of concernthat in a number of cases the cortical pres-sures during hypotension were lower thanwhat is considered the "critical" level inpatients not subjected to arteriolar dilata-tion, i.e., 50 mm. Hg.16 In several patientsthe recorded levels were below what isbelieved to be the necessary minimum inthe presence of complete arteriolar dilata-tion, i.e., 32 mm. Hg.9 Such a state of affairscould bring about a localized arrest of cir-culation, with resulting hypoxia of cerebraltissues.

E. Electrocardiagram and pulse rate. Al-terations in the electrocardiographic patternassociated with hypotension were minimal,even when critical arterial pressures wereapproached (Figs. 7 and 8). In some pa-tients occasional ventricular extrasystoleswere seen, but these did not persist. In al-most every patient, the onset of the gangli-onic blockade was associated with a tachy-cardia. The increased pulse rate persisted asa rule until normal tension was restored. Apossible explanation for this lies in the pre-dominant influence which the parasympa-thetic system is acknowledged to exert oncardiac function under normal circum-stances. When the ganglionic blockadeabolishes all parasympathetic stimuli, theheart ceases to be controlled in this way,and assumes an independent rate, which isfaster than previously.

F. Blood volume replacement. One of thefactors upon which the safety of the hypo-tensive technic depends is adequate returnof venous blood to the heart. With theabolition of peripheral vascular mechanismswhich tend to regulate the volume of circu-lating blood, it becomes important to main-tain the total blood volume at all times.This can be done only by replacing bloodas it is lost. Relatively small amounts ofoozing or hemorrhage, totaling 300 to 500

ml., are reflected rapidly in the general con-dition of the patient. It is remarkable to seehow quickly replacement of blood which islost will improve the cardiovascular statusof the patient. In this series the averageamount of blood given to each patient was1250 ml. Several required none, whereasothers received up to 5,000 ml. This technicshould not be employed primarily to saveblood.

G. Liver function and electrolyte bal-ance. Bromsulfalein liver function testswere normal in seven patients preopera-tively. After operation three of these pa-tients showed no change, while four re-vealed retention of the dye varying from10 per cent to 30 per cent after 45 minutes.These abnormalities could well result fromtissue hypoxia occurring at the time ofhypotension, although one cannot rule outfactors associated with anesthesia and oper-ative procedures themselves. Completeelectrolyte studies were made in 11 patientspostoperatively, and in only one was theelectrolyte balance disturbed.H. "Critical" arterial pressure levels.

Probably the entire crux of the safety ofthis technic hinges upon the duration andextent to which the arterial pressure maybe reduced without irreversible injury tosuch organs as the brain, heart, liver andkidneys. Theoretically as noted above, thecritical pressure in the capillaries whichtends to balance normal fluid exchange atthis level is 32 mm. Hg. If arteriolar tone isabolished completely, the pressure requiredto maintain the forward flow of bloodshould be only a few mm. Hg higher, pro-viding gravitational circumstances do notact against this pressure. In other words,hypothetically an arterial pressure of 40 to50 mm. Hg should provide adequate circu-lation when complete arteriolar dilatationis present.

It is interesting to examine the clinicaldata reported herein to see if there is anyevidence to support or negate this hypothe-

151

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ANESTHESIA RECORDDUKE HOSPITAL.

Annals of SurgeryFebruary, 1956

1447

4B o P

C0A4 GE CANISTER A

HU sT^D 10: 30 A. M.

."Ro lftls.. 7:00 P. M.PREMEDICATON

Demerol. 100 mg.Atropine, 0. 6 mg.

0. T, and N. R.

+4Orotracheal 7

2 Regitine, 5 mg. I. V. (12:22) a

Hexamethonium, 50 mg. I. V. (12:2.)Levophed, 20 gtts/min. (12:30-12:34),o

A 209 Trilene' Pentothal 500

E Anectine 300

DIAG Rigtfroal CPrai fouSOET1 Right frontal craniotomy for aneurysm

s G Drs. Bloor, Wrenn

-Drs. Bowers. Stephen

FIG. 5. 1447. Same patient as Figure 4, 14 days later. Administration of Regitin, 5 mg.followed by Hexamethonium, 50 mg., produced satisfactory hypotension for ligation cerebralaneurysm. Lowest arterial pressure was 40/30 for 20 minutes. Patient reacted satisfactorily afteroperation, but died 48 hours later with marked cerebral edema. Hypotension was not impli-cated in demise.

sis. Such clinical results cannot be exposedto meticulous scrutiny, since so many vari-ables enter into the consideration of eachindividual patient. However, the arterialpressures recorded are accurate inasmuch as

they are derived directly from the radialand cortical vessels. Twenty-six patients hada radial systolic arterial pressure of 50 mm.Hg or less for periods varying from five to45 minutes (Table VI). Of these patients,ten failed to survive after operation anddied at intervals ranging from 12 hours tothree months thereafter. As will be ex-

plained below, the demise of several ofthese patients could be explained entirelyor in part on the pathologic condition en-

countered. Sixteen patients with this severe

degree of hypotension recovered from theiroperations.

It is of importance to note that six of the

ten unsuccessful results were patients suf-fering from recognizable hypertension priorto operation. In the entire series there were

seven other patients with preoperative sys-

tolic arterial pressures of 160 mm. Hg or

higher. In these patients, with one excep-

tion, the systolic pressure during hypoten-sion was not allowed to fall below 70 mm.

Hg. All recovered uneventfully from theirprocedures. The apparent danger in allow-ing marked hypotension in previously hy-pertensive patients receives some supportfrom the electroencephalographic evidencereported by Bromage.6

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FIG. 6. C97983. Comparison of direct radial arterial pressures and those obtained withconventional arm cuff Tycos manometer. Note cuff pressures are higher than direct readings,but are unobtainable at systolic levels below 65 mm. Hg.

In answer to the question whether a sys-tolic arterial pressure of 50 mm. Hg or lesscan be considered "safe," these findingsmust be considered equivocal. Certainly amajority of patients who are normotensivepreoperatively can recover from such epi-sodes with no apparent irreversible lesions.Indeed, there were seven patients (Figs. 4and 5) whose mean radial arterial pressurefell below what is considered the necessaryminimum for tissue oxygenation, i.e., below32 mm. Hg. The only patient who did notrecover satisfactorily in this group was onewho was acutely ill with a recent subarach-noid hemorrhage. At the same time, itseems that hypertensive patients cannotwithstand to the same degree such pro-

found alterations in circulatory dynamics.The overall conclusion tends to support thefeeling that such marked reductions in arte-rial pressure cannot be considered in thebest interest of the patient unless judgednecessary for the best chance of survival.

MORTALITY CONSIDERATIONS

The eventual assessment of any new tech-nic in surgery or anesthesia must be basedon its associated hazard to the patient. Inthe clinical practice of neurosurgery, it isoften difficult to be precise about cause andeffect relationships. More than one, indeedseveral, factors may contribute to a disap-pointing result. Opinions of the on-the-spotobservers are necessary evidence in arrivingat a final decision.

153

H.Ti 9wJ C97983PARASAGIfTAL MEN INGIOMA

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STEPHEN et al. Annals of SurgeryFebruary, 1956

0.5. 046401 57 YEARS

LEFT OCCIPITO-TEMPORAL GRANIOTOMY, WITHINCOMPLETE RESECTION GLIOSLASTOMA MULTIFORME

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In this series of 59 patients and 60 opera-tions, the all-inclusive mortality at the timeof writing is 33.9 per cent (20 patients-Table VII). Five of these patients recoveredcompletely from surgery and succumbed atintervals varying between 24 days and eightmonths after operation. The patient surviv-ing only 24 days died from sudden pul-monary embolus, proved at autopsy. It isbelieved that the production of hypotensionclearly is unrelated to the fatal outcome inthese patients. Therefore, one may reducethe mortality rate at once to 25.4 per cent.A second group of patients were so seri-

ously ill preoperatively that a successfuloutcome would have been a miracle indeed.There were three such patients, all sufferingfrom recent rupture of a cerebral aneurysm.All were brought to the operating room in

a moribund condition, two having no spon-taneous respirations prior to operation. Theseverity of the patient's disease overshad-owed any other factor as a cause of death.The patients lived for 12, 16, and 48 hoursfollowing operation. Therefore, the poten-tial mortality rate associated with the hypo-tensive technic per se can be reduced againto 20.3 per cent.

In a third group of patients, the nature ofthe pathological lesions found at operation,or the type of surgical interference, weresuch as to preclude, in the opinion of theneurosurgeons, a favorable outcome. Pastexperiences indicated that the mortalityrate was high in such patients.One patient (Table VII, patient 11),

had a hydrocephalus preoperatively whichwas secondary to subarachnoid bleeding.

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Volume 143 INDUCED HYPOTENSION FOR NEUROSURGICAL PROCEDURESNumber 2

This persisted and became more acute inthe postoperative period in spite of severalefforts to alleviate it. Death after threemonths in this instance was considered dueclearly to patient's disease, and not opera-tive interference.

Patient 16 died 15 days postoperatively,with a secondary rupture of the cerebralaneurysm. It was not believed her opera-tion contributed in any way to her subse-quent rapid demise.A third patient (14) had a subtotal re-

moval of a meningioma involving the mid-dle and inner third of the sphenoid ridge.Her course postoperatively showed the in-creasing cerebral edema so common inthese patients. It was not believed that thehypotension at time of operation contrib-uted in any way to her death in 48 hours.

Patient 18 developed a thrombosis of theinternal carotid artery which led to herdeath 72 hours after operation. Hypoten-sion was not believed a contributing causein this patient.Four other patients, all dying within four

days of operation, had ligations of aneu-rysms and developed severe cerebral ede-ma. Their postoperative course was similarto that seen in other like situations wherehypotension was not employed. It was theconsensus of opinion of those intimatelyconcerned with these patients that hypo-tension was not a major contributing factorin their deaths. However, it could not beruled out definitely, particularly since twoof these patients were hypertensive pre-operatively.

Autopsies conducted on two patientswere of considerable interest and value.

Case 1. Patient number 10. This 57-year-oldwhite male had a left occipitotemporal craniot-omy with incomplete resection of a large glio-blastoma multiforme. Preoperative blood pressurewas 160/110, and this was maintained during thehypotensive phase, lasting 2 hours, at 100/70. Thepressure fell to 35/25 for a 10 minute period.Postoperatively the patient failed to respond, andin 6 houirs the hone flap was removed due to

increase in cerebral tension. The patient's condi-tion continued to deteriorate, and he died in 36hours. Postmortem showed a transtentorial hernia-tion of the cerebrum, with scattered areas of con-gestion, hemorrhagic infarction, and neuronal necro-sis in the mid-brain and pons. It is unlikely thatthe histological changes in this patient were adirect result of induced hypotension. The courseof terminal events probably was respiratory fail-ure secondary to the brain damage resulting fromthe transtentorial herniation and infarction of thebrain.

Case 2. Patient number 13. This 49-year-oldwhite male had a right frontotemporal craniotomywith clip ligation of an aneurysmal sac of theright middle cerebral artery. Preoperative bloodpressure was 170/110, and this was maintained atan average level of 70/50 during the hypotensivephase, falling to 50/30 for one 30 minute period.Postoperatively, the patient responded favorablyfor 24 hours, but then went progressively downhilland died 72 hours later. Autopsy showed neuronaldegenerative changes in the left cortex of the brain,that is, the side opposite to the site of operation.Superficially, this finding would be compatiblewith neuronal lesions associated with tissue anoxiaproduced by induced hypotension. It is interestingto leam that two patients who have died withacute subarachnoid hemorrhage within the lastsix months in this hospital, but who have not cometo operation, have shown similar neuronal altera-tions in the cortex opposite to that of the principallesion. Thus, the lesions noted above certainly mayoccur in the absence of induced hypotension andoperative intervention in patients suffering fromcerebral aneurysm. In our opinion, one cannotincriminate hypotension as a pricipal cause ofdeath in this patient.

This group of ten patients represents aborderline classification in which reasonabledoubt can be cast as to the true and princi-pal mechanism of death. In two patients ofthis group autopsies were performed, asnoted above, and direct examinations failedto show histological changes which could beassociated directly with the induced hypo-tension. Giving the technic of hypotensionbenefit of the doubt, one can reduce thepotential mortality rate directly ascribed toit to 3.4 per cent.The remaining two cases constitute a

fourth group in which it is difficult to ruleout hypotension as a major contributing

155

STEPHEN et al.

FIG. 8A

factor to mortality. Patient number 19 hada right frontal craniotomy and subtotal re-

section of a suprasellar meningioma arisingfrom the tuberculum sella. The tumor sur-rounded the vessels closely. Preoperativelythe blood pressure was 110/80, and duringthe hypotensive phase it was maintainedabout 80/65. For one ten minute period itfell to 40/20. The patient did not recoverfrom operation and died 24 hours laterafter body temperature had risen to 40° C.with accompanying signs of greatly in-creased intracerebral pressure. It was

thought that death was due to hypothala-mic involvement associated with cerebral

edema. Autopsy was not obtained. The con-sensus of opinion was that this patient didnot respond as might have been expectedfrom the surgical lesion encountered.The second patient in this group, number

20, was a 37-year-old white female hyper-tensive who had a left frontal craniotomyand clip ligation of an aneurysm lying at thejunction of the left anterior cerebral arteryand the anterior communicating artery.Preoperatively the blood pressure was220/130, and it was maintained about110/90 during the period of hypotension.For one ten minute period it fell to 40/20.This patient never responded postopera-

156

Annals of SurgerFebruary. 1556

INDUCED HYPOTENSION FOR NEUROSURCICAL PROCEDURES

DISSECTING ANEURYSM B.R ?O/ 50

::CLOSMNG DURA E

FIG. 8B

tively, and died 28 days later following an

arteriogram. Her behavior following opera-tion was similar to that of a decerebrateindividual. It was felt that the inducedhypotension in this hypertensive arterio-sclerotic patient contributed directly to herpostoperative state and eventual death. Un-fortunately an autopsy was not performed.A total of five autopsies were obtained in

this series. Histological examinations of thebrain, liver, Iddney and heart in each pa-

tient showed no evidence of local tissueanoxia such as might be associated withprofound hypotension. The one possibleexception to this is patient number 13,quoted above, in whom cortical cellularchanges in the side contralateral to opera-

tion could have been initiated by induced

hypotension. However, such changes mayoccur in the absence of operation and hypo-tension.

DISCUSSION

"The modern devotion to Science, whichis exact, as opposed to Art, which is notexact, has one disastrous consequence whenapplied to the practice of medicine. Thedevotees of the 'scientific' attitude are wontto seek 'indications' and 'contra-indications,'and to apply them by rule of thumb to allpatients who exhibit certain symptoms orsigns. 'Routine' should have no place inmedicine, for all 'indications' and 'contra-indications' are relative, rather than abso-lute. Each case is a problem in itself, andmust be so considered."8

157

Vohlime 1443Number 2

STEPHEN et al. Annals of SurgeryFebruary, 1956

A decision to employ induced hypoten-sion during a surgical procedure is an indi-vidual problem, and should be undertakenonly after agreement between the surgeon,internist and anesthesiologist. The experi-ences recounted above tend to emphasizecertain factors of importance in the choiceof patients and the conduct of the interven-tion.

(a) Patients suffering from hypertensivearteriosclerotic heart disease do not with-stand this gross cardiovascular alterationwith impunity. They are very sensitive tothe action of ganglionic-blocking com-pounds and do not appear to recover fromthe effects of blockade as rapidly as doother patients.

(b) Great variation exists in individualsensitivity to hypotensive compounds. Oc-casionally a patient is seen who appearsunder anesthesia to be totally resistant tothe action of these drugs. The reason forthis is unknown, but there is some indica-tion that the concomitant administrationof an adrenolytic compound will permithypotension to develop.

(c) Blood pressures obtained by theconventional arm cuff method cannot beconsidered reliable, and may give a falsesense of security or, in the lower ranges oftension, may be non-existent. Security inthis regard can be obtained only by directreadings from an indwelling catheter in anartery.

(d) Evidence is presented to suggestthat, even in the reverse Trendelenburgposition, a relatively constant gradient ex-ists between radial and cortical artery pres-sures, both before and after the productionof hypotension. However, it should be notedthat when the mean radial pressure is lessthan 55 mm. Hg that of the cortical vesselsmay be low enough to question whethernormal capillary exchange can occur as itshould physiologically.

(e) A "critical" level of hypotension can-not be designated to include all patients. It

seems logical to state that the mean arterialpressure should not fall any lower than iscompatible with the requirements of thesurgical procedure. Sometimes as in opera-tions on aneurysms in difficult positions thismay be 50 or 40 mm. Hg. Such low pressureshould be maintained as short a time aspossible, and may be reversed with vaso-pressors such as levoarteronal. In hyper-tensive patients, the fall in arterial pressureshould be restricted as much as possible.

(f) The mortality statistics indicate thatthis technic of chemical hypertension issufficiently hazardous that it should not beundertaken unless the physical conditionof the patient appears to allow it, andunless the physicians concerned feel thatthe extra danger involved is necesary inorder to complete successfully the operativeintervention.

(g) The experiences noted above leaveus with the impression that more basicstudies are necessary before the technicof induced hypotension can be employedwith impunity for a variety of surgical pro-cedures.

SUMMARY

1. A review is presented of 59 patientssubjected to indTuced hypotension by meansof chemical drugs during neurosurgicaloperations.

2. A method is discussed of recordingdirectly radial and cortical arterial bloodpressures.

3. The merits of hexamethonium bro-mide, Arfonad and Pendiomide as gangli-onic-blocking compounds are indicated.

4. Observations noted at various levelsof hypotension are presented.

5. The mortality encountered during thisseries of patients is investigated, and anattempt made to establish the role of hypo-tension.

6. Some of the hazards of and indicationsfor this technic are discussed.

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Volume 143 STEPHEN et al.Wumhe 2.

BIBLIOGRAPHY

Anlyan, W. G., W. W. Shingleton, W. R. Ben-son, C. R. Stephen, M. Salem and H. M.Taylor: A Study of Liver Damage Follow-ing Induced Hypotension. Surgery (in press).

2 Armstrong-Davison, M. H.: The Case AgainstHypotension. Anesthesia, 8: 255, 1953.

3 Asquith, E.: Controlled Hypotension in Surgery.Can. Med. Assoc. J., 67: 421, 1952.

4 Boyan, C. P., and A. Brunschwig: HypotensiveAnesthesia in Radical Pelvic and AbdominalSurgery. Surgery, 31: 829, 1952.

5 Bromage, P. R.: Effect of Induced VascularHypotension on the Liver. Lancet, 2: 10,1952.

fi6-- : Some ElectroencephalographicChanges Associated with Induced VascularHypotension. Proc. Royal Soc., Med., 46:919, 1953.

Enderby, G. E. H.: Controlled Circulation withHypotensive Drugs and Posture to ReduceBleeding in Surgery: Preliminary Results withPentamethonium Iodide. Lancet, 1: 1145,1950.

8 Gillespie, N. A.: Wisconsin Study CommissionBulletin, 6: 1, 1954.

GCriffiths, H. W. C., and J. Gillies: Thoracolum-bar Splanchnicectomy and Sympathectomy.Anesthetic Procedure. Anesthesia, 3: 134,1948.

10 Hampton, L. J., D. M. Little, M. L. White,E. M. Fuller and D. C. Grosskreutz: An As-sessment of Complications in 21,000 Cases ofControlled Hypotension in Anesthesia. Scien-tific Exhibit, A. S. A. Annual Meeting,Philadelphia, 1952.

Morris, G. C., J. H. Moyer, H. B. Snyder andB. W. Haynes: Vascular Dynamics in Con-trolled Hypotension. Ann. Surg., 138: 706,1953.

12 Moyer, J. H.: Personal communication.13 Moyer, J. H., R. A. Huggins, C. A. Handley and

L. C. Mills: Effect of Hexamethonium Chlo-ride on Cardiovascular and Renal Hemo-dynamics and on Electrolyte Excretion. J.Phar. and Exp. Ther., 106: 157, 1952.

14 Nicholson, M. J., S. J. Sarnoff and J. P. Crehan:The Intravenous Use of a Thiophanium De-rivative (Arfonad-RO-2222) for the Produc-tion of Flexible and Rapidly Reversible Hy-potension during Surgery. Anesthesiology, 14:215, 1953.

1 Stephen, C. R., B. Woodhall, G. Odom andW. K. Nowill: Methods for Reduction of Sur-gical Blood Loss. Kentucky State Med J., 52:344, 1954.

VWoodhall, B., G. L. Odom, C. R. Stephen, C. L.McClure and W. B. Neill: Cerebral Intra-vascular Pressure in Chemically Induced Hy-potension. Arch. Surg. (In press.)

159