The Utilization of Moderate Hypothermia as an Adjunctto General Anesthesia for Extensive Surgical Procedures.* S.N. Albert, M.D., W. A. Spencer, M.D., H. J. Ecclston, Jr., M.D., J. Shibuya, M.D., C. A. Albert,** M.D., and J. R. Thistlethwaite, M.D., Washington, D. C. Departments of Anesthesiology and Surgery, District of Columbia General Hospital S T E N S I V I< SUR G I CAI PR 0C ED U IR E S on poor - r i sk patients will result in a significant morbidity and mortality rate. Prolonged deep general anesthesia certainly is a contributory factor. Techniques which will lessen any of the deleterious effects of anesthesia will be beneficial. Moderate hypothermia appears t o be a valuable adjunct in thisregard. Sixty cases representing a variety of major dissbilities andrequiring extensive surgical procedures have been operated upon withthis technique with encouraging results. It is the purpose of this paper t o describe our technique of hypo-thermia, to discuss the rationale for its use i n extensive surgical pro-cedures, and t o record some of our observations. Technique 9 HAKBITUKATE is given t o the patient a t bedtime the eve- ning before the operation is scheduled. No other premedicationis administered. General anesthesia is induced with 2.5 per cent Petitothal sodi-um,@ after which the patient is taken into the operating room andplaced tipon a water-cooled mattress. Electrocardiograph electrodesare placed on all extremities and connected t o a Cambridge Cardio-scope. ERG recordings are made intermittently by a direct scriherelectrocardiograph attached t o the cardioscope. An infusion of 1 :SO0 Arfonad@* and an infusion of Neo-syneph-rille@ containing 20 milligrams in 500 cc. normal saline are prepared.These solutioiis are connected t o the infusion system with appro-priate stopcocks so that they may be administered as desired. Temperatures are recorded by a T,eeds & Northrop temperaturerecording machine from a thermocouple lead placled in the rectum,or in t h e esophagus, depending on the site of the operation. Readingsare also made directly with a Telethermometer. *Presented before the Thirtieth Congress of Anesthetists, Arlnual Meeting of tlic Members u f thcInternational Anesthesia Research Society, Miami Beach, Fla., April 9-12, 1956. **Presently Captain M. C. U. S. Army. Acknowledgment and appreciation to Dr. Joseph Fazekas, Chief (if Staff, D. C. GeneralHospital, Washington, D. C . , for 1,erforming the studies on (‘erebra1 Hemodynamics and Metabolism. *Arfonad@generously supplied by H. LaRoche Co.
Moderate Hypothermia as an Adjunct to General Anesthesia As the level of general anesthesia is deepened a muscle relas-a n t (d-tubocurarine) is administered. A cuffed endotracheal tube isinserted under direct vision. A mixture of 50 per cent nitrous oxideand 50 per cent oxygen with intermittent vaporization of ether isadministered in a semi-closed system. T h e patient’s respiration isassisted or controlled by a Blease Pneumoflator, which is a mechani-cal respirator. This respirator has a 5 cm. water negative pressurephase. T h e respiratory rate is regulated a t 16-20 per minute. T h epositive pressure phase is regulated t o deliver a tidal volume of400 - 600 CC. T h e cooling of the patient is started by circulating ice waterthrough the mattress with a Thermorite unit. I n addition to themattress, ice bags are placed on the anterior surface of the body. Cooling is facilitated by intermittent administration of Arfonadt o avoid reflex vasoconstriction. T h e systolic blood pressure is main-tained a t 10-40 mm. of Hg below the initial level. Arfonad is notnecessary if there has been a fall in the systolic blood pressure follow-ing administration of Pentothal and ether. Shivering is to be avoided. However, if shivering does occur,the level of anesthesia is deepened until the shivering disappears. TARLE 1 Operative Procedures No. of Cases Thoracotomies 17 Broncho-esophageal fistula I Lobectomy S Pneumonectomy 3 Segmental resections 1 Mpdiastinal tumor 1 Resection of coarctation 1 Resection of aneiirysm 1 Resection of patent ductus 7 Insertion plastic aortic valve 1 Tetralogy of Fallot 1 Neck 2 Thyroidectomy for loxic goiter 2 Abdominal 26 Gastric exploration 1 Gastric resection 10 Pancreatic resection 7 Colon resection 4 Retroperitoneal tumor 1 Common duct exploration 3 Portal caxal shunt 2 Splenectomy 2 Resection of aneurysm 1 Pelvic IS Radical hysterectomies (Wertheim) 10 Hysterectomy-gas gangrene 1 Abdominal perineal resection of rectum 4 Total No. of Cases 60 571
Albert, Spencer, Ecclston, Shibuya, Albert and ThistlethwaiteShivering cannot be eliminated by ganglioplegic drugs unless there isa concomittant depression of the central nervous system. I n approximately 30 - 60 minutes the rectal temperature will havefallen t o 35 - 34 degrees C. W h e n this temperaturie is reached the icebags are removed. T h e patient is then positioned and the operationis started. T h e circulation of the ice water in the mattress is interruptedwhen rectal temperature reaches 33" C. T h e patients temperatureis maintained between 3 2 - 3 0 " C by varying the temperature of thewater circulating in the mattress. T h e systolic blood pressure is maintained at a level above 90inin.H g . If the blood pressure falls below this level the patient isplaced in moderate Trendelenburg position. If further support isnecessary, Neo-synephrine 20 tng. per 500 cc. infusion is started. Whenever signs of ventricular irritability or cardiac arrythmiasare seen on the cardioscope screen, t h e Arfonad infusion is startedregardless of the level of the blood pressure. As :;eon as the cardiacrhythm reverts t o normal the infusion is stopped. T h e Neo-synephrineinfusion is begun when necessary t o combat the hypotensive effectof the Arfonad. Rewarming of the patient is accomplished by circulating warmwater through the mattress. W h e n the temperature reaches 33" C.the patient is transferred to the recovery room. All patients are awakea t the termination o the surgical procedure. f Report of Cases and ObservationsS I X T Y P A T I E N T S have been operated upon with moderate hypo- thermia as an adjunct to general anesthesia. Tihis report does notinclude patients with cranial1 or intracardiac operations. A widevariety o surgical procedures is represented in this group of sixty fpatients, and the different operative procedures are listed in table 1. - TABLE 2 A g e Distribution of Cnscs Age No. of Cases P e r cent Group per centUnder 4 weeks 1 3.310-20 years 3.321-29 years 5.0 11.730-39 30.040-49 15.0 45.050-59 13.360-69 20.070-79 3.380.90 4 6.7 43.3 5i2
Moderate Hypothermia as an Adjunct to General Anesthesia TABLE 3 Classification o f Cases Patients with cardiovascular disease-confirmed by E.C.G. 26 Poor-risk patients 26 Fair-risk patients 26 Good-risk patients 8 T h e ages of these patients ranged from 6 hours t o 89 years (seetable 2 ) . Twenty-six were classified as poor-risk patients, eitherbecause of their particular existent disease, or because of their seripuscardiovascular or renal disease. Twenty-six were classified a s fair-risk patients. Most of the patients in this group had pulmonarytuberculosis or malignant diseases. Eight patients were classified asgood risks. Twenty-six patients had evidence of cardiac disease, ofwhich twelve had EKG evidence of coronary insufficiency (table 3 ) . There were n o serious complications attributable to the hypo-thermia or to the anesthesia. There was only one instance of ven-tricular fibrillation. This developed in association with a seriousblood loss in a patient undergoing an operation for a ductus arteriosus.This patient died from an uncontrolled hemorrhage. There were six fatalities during the first postoperative week. Twoof these deaths occurred after esophageal resections, one deathoccurred from a leaking suture line following a repair of a tracheo-esophageal fistula, and the fourth death was due to hepatic comafollowing a portocaval anastomosis (table 4). It is striking to notice how hypothermia reduced the amount ofanesthetic agents required by the patients.2 On the average, onlyabout one-half of the expected amount of Pentothal and ether wasnecessary t o maintain a satisfactory level of anesthesia. Table 2 showsthe comparison of the average amount of Pentothal and ether requiredfor 10 patients who had operations for radical hysterectomies, and 10patients who had operations for gastric resections with a similarnumber of patients undergoing the same procedures without hypo-thermia (table 51. TABLE 4 Mortality During First Week Post Surgery Age Case Time of Death Cause16 yrs. Resection patent ductus I n 0. R. Bleeding49 yrs. Gastric exploration 1 hour p. 0. Bleeding58 yrs. Esophageal resection 24 hours p . 0. Cardiac failure 6 hours Broncho esophageal fistula 3 days p. 0. Midiastinitis5 5 YTS. Esophageal resection 4 days p. 0. Cardiac Failure31 yrs. Porta caval shunt 5 days p. 0. Hepatic coma 573
Albert, Spencer, Ecclston, Shibuya, Albert and Thistlethwaite TABLE 5 Radical Hysterrctomirs Comparison of Two G r a s p s of Casrs Hypothermia With WithoutNumber of cases 10 10Duration of anesthesia in hrs. 5 $4 5Pentothal in mgms. 750 1250Ether in C.C. 75 140Curare in mgms. 20 30Recovery time in hrs. I n 0. R. 1:: hrsUrine output in first 24 hrs. 2100 C.C. 750 cc. Gastric Resections Comparison of Two Groiips of Cascs Hypotherniia With WithoutNumber of cases 10 10Duration of anesthesia in hrs. 4 3Pentothal in mgms. 800 1.300Ether in cc. 80 160Recovery time in hrs. I n 0. R. 1y;Urine output in first 24 hrs. 1800 c.c 700 c.c From the anesthesiologists point of view the patients are easiert o manage with these reduced amounts of anesthetic agents. Minimalamounts of these anesthetic agents are required to maintain the pa-tient in the proper anesthetic level for adequate relaxation. Thereis little fluctuation in systolic blood pressure throughout the proceduresince the hypotension resulting from a too deep level of anesthesiacan be avoided. I n addition, hypothermia protects the central nervous systemduring periods of hypotension and aiioxemia. Prolonged periods withthe systolic blood pressure below 90 mm. Hg are tolerated withoutill effect. Twenty-seven patients, or nearly half of the total number, demon-strated myocardial irritability during the cooling process. Arrythmiaswith premature ventricular contractions were the most constantchanges (table 4 ) . I n all instances normal cardiac rhythm waspromptly established by starting the infusion of Arfonad. TABLE 6 Temperaturr Variations Incidence o f Myocardial Irritability Average temperature 30-31" C Variations between 28-33.5"C E.C.G. changes during cooling 28 Patients controlled with Arfonad Temperatures a t which E.C.G. occurred 3 5 ~ 3 1C ~ 574
Moderate Hypothermia as an Adjunct to General Anesthesia Patients operated upon under hypothermia have less adreno-cortical response than is expected for patients having similar pro-cedures without h y p ~ t h e r m i a . ~ They are alert and awake almostimmediately after the completion of the operation, and they seldomhave the typical “knocked out” appearance which the average patientdemonstrates after a major procedure. They tend t o excrete ratherthan t o retain water and sodium as one might expect5 A urinaryoutput of 1500-2000 cc. in the first 24 hours is not unusual. Atten-tion t o fluid replacement is necessary during the early postoperativeperiod. Before the authors were acquainted with this post-hypo-thermia diuresis with a loss of sodium, two patients developed saltdepletion syndromes. These two patients had received postoperativefluids in the usual manner, with saline solutions being avoided duringthe first 48 hours (table 5 ) . Details of this altered corticoid response in these cases is t o bepublished a t a later date. Studies have been made of the water andthe electrolyte metabolism, the steroid levels in the blood and theurine, and the serial blood and plasma volume determinations.* Discussion31 P A T I E N T U N D E R G O I N G an extensive surgical procedure is subjected to considerable trauma and stress from which he hasto recover in order t o make the surgical intervention a success. I norder to minimize the role of anesthesia as a stress stimulus6attempts have been made to administer a combination of drugs, eachacting on a part of the nervous system in order t o obtain the desiredhypnosis, analgesia and relaxation? A t best there still remains sig-nificant stress due to anesthesia. Since hypothermia reduces theamounts of the general anesthetic agents required, and, in addition,produces a physiologic depression of tissue metabolism, it will reducethe stress of anesthesia. Because all of the body enzymes act a t an optimum temperature,the reduction of body temperature will result in depressing theenzymatic action. Metabolism of all the organs and systems of thebody is thus reduced. This reduced metabolism with reference tothe brain will dull the sensorium; hence, the amounts of anestheticagents needed will be lessened.R Normally the brain cannot withstand an oxygen deficit; it isdependent entirely on the minute t o minute blood flow for its oxygensupply. If the circulation is interrupted for more than a few minutesirreversible damage t o the brain cells ensues. Whenever hypotensionoccurs, either due to blood loss, hypotension intentionally induced byganglioplegic agents, or from deep levels of anesthesia, physiologicaladaptations occur in an attempt to maintain an adequate oxygen *Project partially supported by U. S. Atomic Energy Commission under contract A T (30-1) 1821.
TABLE 7 Cerebral Hernodynamics and Metabolism Changes* Mean Values and Mean Exfierimental Differences Alcohol Thorazine Hypothermia 3.8 Effect of Effect o fber of Cases Studied 8 Alcohol 7 Thorazine 3 Contro: Exy. Diff. Control Exp. Diff. Control rterial Pressurel Artery mm H g 98 -9 113 -36 142l Blood Flow 52.5 +3.5 40.9 - 2.1 46.6 /100 grs. brainvascular** 2 -0.3 2.9 - 0.7 2.3cel 0 s Consumption 2.8 -0.1 2.4 + 0.1 2.7/lOO grs. brainVenous Oxygen 5.94 -0.74 5.91 + 1.00 5.61e volume %ebral vascular resistance in mm. of Hg/cc hlood/100 gm. of hrain/min.einberg and Steads modificationz4 of Kety and Schmidts procedure% for the determination of cerebral blood flow was applieddata on Cerebral Hemodynamics and Metabolism are through the courtesy of Dr. Joseph F. Fazekas, Chief of Staff, District of C pital.
Moderate Hypothermia a s an Adjunct to General Anesthesia TABLE 8 Cerebral Metabolrc Rate C. C. O z / l O O gms. brain/minute Age Control after Pentothal After Reduction 3" C 7% Reduction 15 3.2 1.9 40.6% 59 2.7 1.0 62.9 68 2.2 0.7 68.0supply t o the central nervous system. These changes are either anincrease in the rate of blood flow t o the brain, due to the loweredcerebral vascular resistence, or are due t o increases in the arterial-venous oxygen difference of the cerebral circulation (table 8 ) . I nspite of the adaptations, the cerebral cortex is on the verge ofischemia.ll l2 T h e only way to protect the brain from ischemia during hypo-tension is t o reduce the oxygen requirement of the brain. T h e centralnervous system depressants will reduce the cerebral metabolic rateonly to a limited extent. A physiologic way t o reduce the oxygenrequirement of the central nervous system is to reduce the body tem-perature. Moderate hypothermia ranging between 32 - 30" C. reducesthe cerebral metabolic rate a n average of 50 - 75 per cent.13 Appar-ently there is no linear proportion between the degree of coolingand the reduction of the cerebral metabolic rate in man14 (table 8). Marked reduction in the cerebral metabolic rate has been ob-served with a reduction of 1 C. in the body temperature. T h e cerebralmetabolic rate decreased 50 per cent or more by the time the bodytemperature reached 30" C. in all of the individuals studied. I n allinstances there was a marked increase in the cerebral vascular resist-ance in spite of hypotensive levels of blood pressure which wereproduced by vasodilator agents. W i t h this reduction in the rate ofblood flow there is only a small variation in the arterio-venousoxygen difference ; thus, the cerebral metabolism is depressed almostproportionately to the reduction of the blood flow. Studies of cerebralmetabolism have been made utilizing Thorazine,@ Arfonad, alcoholand Pentothal at levels of blood concentration equivalent t o thosefound in patients under hypothermia. T h e results have been shownthat these drugs used alone or in conjunction with each other hadlittle if any effect on the cerebral metabolic rate. Therefore it isconcluded that the reduction in cerebral metabolism observed underhypothermia is due entirely t o the effect of hypothermia rather thanto any drug or combination of drugs used.15 l6 l 7 Nevertheless, oneshould be cautioned against hypotension due t o excessive blood loss.As seen in table 7 , the cerebral blood flow is markedly reduced inpatients with hypothermia. This coupled with a deficient bloodvolume may cause a severe ischemia with irreversible damage t o thecentral nervous system. T h e protective effect of lowered cerebral metabolic rate underhypothermia is clinically substantiated by several instances in which 577
Albert, Spencer, Ecclston, Shibuya, Albert and Thistlethwaitepatients have been allowed to remain in a state of hypotension witha systolic blood pressure of 50 mm. Hg for periods of 30 - 45 minuteswithout untoward effects. Recently we were called upon to consult on a most interesting-case* which dramatically verifies this protective effect of hypotherniiaon the brain. A two weeks old infant was left on a door step duringone o Washingtons coldest spells. T h e infant was picked up by fthe hospital ambulance and brought to the emergency room. Noheart beat was heard by several o>bservers, pulse was felt, and the noinfant was pronounced dead. After being in the warin environmentfor over 30 minutes the infant was noted to gasp. The heart beatcould be faintly detected. Rewarming of the infant was continued.T h e rectal temperature was taken with a Teletherinonieter about anhour later and it registered 20" C. V17ith complete rewarming theinfant recovered. I t appears that the severe degree of hypotherniiahad completely protected the infants central nervous system so thata prolonged period of cardiac standstill was tolerated. T h e development of cardiac arrhythmias, which may lead to ven-tricular fibrillation, has been the biggest deterrent t o the use of hypo-thermia. I n order to combat this possible complication, attemptshave been made to reduce myocardial work load and myocardialirritability by utilizing certain drugs. It has been the impression of many investigators that there existsa critical tem,perature range (29" -25" C.) in which myocardial irri-tability is most prone t o occur.1s InContrary t o this, we have foundthat premature ventricular contractions and signs of myocardialirritability may occur a t any stage of ?he cooling, especially in thepoor-risk and the elderly patient. W e encountered this phenomenonwith cooling of 1" C. O u r experience with drugs used in an attempt to control myo-cardial irritability has been most encouraging. T w o drugs, Thora-zine** and Arfonad, have been utilized. T h e former drug has beenshown t o have antifibrillatory properties in dogs.20 21 2 2 Both ofthese agents will produce peripheral vasodilation and hypotension,thus decreasing the work load on the heart. Evidence to date indi-cates that both drugs decrease myocardial irritabdity. These twoproperties make them of value in controlling arrhythmias, and, inaddition, facilitate cooling by their vasodilation effect during hypo-thermia. Thorazine has two distinct disadvantages in this respect.The first is that the induced hypotension cannot be controlled ant1cannot be reverted with therapeutic doses of vasoconstrictors ; sec-ondly, there is a troublesome tachycardia associated with the use of *Case presented here by Courtesy of Dr. Hoeck, Chief of Pediatrics at D . C. General Hospital. *"Thorazine generously supplied by Smith, Kline & French Laboratories 578
Moderate Hypothermia as an Adjunct to General Anesthesia Fig. I Fig. 2 579
Albert, Spencer, Ecclston, Shibuya, Albert and Thistlethwaitethis drug, O n the other hand, Arfonad has neither of these properties.There is no tachycardia, and the hypotensive effect can be controlledeasily and reverted by the administration of Neo-syiiephrine or othervasoconstrictor agents without distracting in the least from its effectof controlling arrhythmias and myocardial irritability. O u r observations in this group of cases indicate that Arfonadhas a direct action on the myocardium. W e have observed arryhthmiaswhich develop in the hypothermic state while the patient is alreadyin hypotension due t o the effect of the anesthetic agent administered.Normal cardiac rhythm is restored when Arfonad is administered. Fig. 4 580
Moderate Hypothermia as an Adjunct to General Anesthesia Fig. 5 Fig. 6There was no further fall in blood pressure. One can attribute theeffect directly as an action on the myocardial tissue, rather than aneffect of Arfonad on the peripheral vascular bed. Also, it is interest-ing to note that the arrhythmia did not recur when the blood pressurewas raised or maintained with Neo-synephrine infusion, and the workload on the heart was increased. The effect of Arfonad on the myo- 581
Albert, Spencer, Ecclston, Shibuya, Albert and Thistlethwaitecardium seems t o persist for a period of 1 - 2 hows. Occasionally we ’noted a recurrence of myocardial hyperirritability which was in turnagain controlled by instilling the Arfonad infusion. These beneficialeffects of Arfonad have been documented several times with continu-ous EKG tracings during the operative procedure showing reversalsof arrhythmias t o normal rhythms (fig. 3 , 2, 3, 3, 5 , 6). Summary Y P O T H E R M I A A P P E A R S t o be a valua.bIe adjunct to gen- eral anesthesia for patients undergoing extensive surgicalprocedures. Hypothermia diminishes the stress of the anestheticagents administered and, in addition, seems t o alter a patient’s normalreaction t o the stress of surgery. T h e technique for indacing hypothermia is briefly presented. A series of sixty patients receiving hypothermia is reported. T h e protecting effect of hypothermia on the cerebral cortex fortolerance of hypotension and reduced blood flow has been discussed. Arfonad has been shown t o be an effective agent for the controlof cardiac arrhythmias and myocardial irritability during hypothermia.I t s action in this regard has been discussed. References 1. Eccleston, H. N., Jr., Coakley, C. S., Alpert, S., Albert, S . N.: A Preliminary Reporton the Combination of Hypothermic and Hypotensive Techniques. Anesthesia aiqd ’4nalgesia.35:4,285 (July-August) 1956. 2. Bering A. E. Taren, T. A,. McMurrey, J. D. and Rernhard, W. F.: Studies of Hypo-thermia in Monk’eys P a i t 11. S. G. 6. 0. 102:2, 134-138 (Feb.) 1956. 3. Steinhurg’R. W., Lennihan, R , Moore, F. D.: Studies in Surgical Endocrinology, Part 11. :Ann. of Surg., 143~2:180-209 (Feh.) 1956. 4. Bernhard, F. W., McMurrey, J. D., Ganong, W . F. and L,enihan, R.: The Effect ofHypothermia on Peripheral Serum Levels of Free 17-Hydroxycorticoids in the Dog and Man.Ann. of Surg. 143:2 210-215 fFeb.) 1956. 5 . MoGer, J. k., and Morris, G. C., Jr.: Renal Functional Response to Hynothermia aridIschemia in Man and Dog. Presented at the National Academy of Siciences, Natronal ResearchCouncil, Washington, D. C. October 28 1955. 6 . Moore, F. D., S;einhurg, R.’ W., Ball, M . R., Wilson, G . and Myrden, J. A , : Studies(in Surgical Endocrinology. P a r t 1. Ann. of Surg.. 141 :145, 1955. 7. Hune D. M.: Effect of Hynothermia on Adrenocortical Secretion in Animals. Presentedat National Academy of Sciences Natlonal Research Council, Washington, D. C., October 38, 1955. 8. Dundee, W. J., Scott, ’W. E. B. and Meshan, P. R.: The Production o f Hypothermia. Ilrit. Med. J. 2:1244 (Dec.) 1953. 9. Po&ius, R. G., Brockman, H., Hardy, L. .R., Cooley, I . A. and DeBakey, .M. E.: The ) Rise of Hypothermia in the Prevention of Paraplegia Following the Temporary Aortic Occlusion.S w g r r y , 36:33-38 (July) 1954. 10. McQuiston W. 0.: Anesthesia in Cardiac Surgery. Arch. S I I Y ! ~ 65392 (Nov.) 1950. ., 11. Fazekas, J: F., Klell. J. and Parrish, A. E.: The Influence of Shock on Cerebral Hemo-dynamics and Metabolism. Am. I . Med. .Scz. 329:l-41-45 (Jan.) 1955. 12. Fazekas, J. F., Alherf, S. N., a i d Alman, R . W.: Influence of ChlorDromazine andAlcohol on Cerebral Hemodynamics and Metabolism. A m . I . Med. Sci., 2 3 0 2 (Ang.) 1955. 13. Bigelow, W. G., Lindsay, W . R..Harrison, R. C., Gordon, R . A. and Greenwood, W. F.Oxygen Transport and Utilization in Dogs at Low Body Temperatures. Am. I . Physzology, 160 :125137 (Jan.) 1950. 14. Albert, S. N. and Fazekas, J. F.; Cerebral Hemodynamics and Metabolism DuringInduced Hypothermia. Anesthesia and Analgesza, 3 5 : 4 , 381 (July-August 1 1956. 15. McMurrey, J. D., Bernhard, W. F., Faren, J. A. and Bernig, E. A , : Studies on Hypo-thermia in Monkeys. P a r t 11. S. G. & 0.. 102:1:75-86 (Jan.) 1956. 16. Hegnaner, A. H. and D’amato, H. E.: Oxygen Consumption and Cardiac Output inHypothermic Dog. Am. I. Physiology, 178:138 (July) 1954. 17. Woodruff, L. M.: Survival of Hypothermia by the Dog. Anesthesiology: 2i410, (July) 1941. 18. Riberi A,, Siderip, H. and Shumacker, H. B., Jr.: Ventriciilar Fibrillation in Hypo-thermic State. &. of Surgery, 143:2:223 (Feb.) 1956.
Moderate Hypothermia as an Adjunct to General Anesthesia 19 Covins B. G Charleson, D. A. and D’amato, H. E.: Ventricular Fibrillation in Hypo-thermid Dog. Ad. I. P i j s i o l o g y , 178:148 (July) 1954. 20. Finkelstein, M., Spencer, W. A,, Hannen, C. S. and Albert, S. N.: Effect of Chlorpro-mazine on Heart Muscle and Its Influences on the Inotropic Action of Three SympathomimeticAmines. Federation Proceedings, 13 :1 (Mar.) 1954. 21. Albert, S. N., Spencer, W. A,, Fiukel:tein, M. and Coakley, C . S.: The Place of Chlor-promazine in Anesthesia. Anesthesia and Analgesza, 3 5 : 2 , 101 (March-April) 1956. 22. Dobkin, A. A,, Gilbert, R. G. B., Melville, K. I.: Chlorgromazine. Anesthesiology,17:l :135-164. 23. Schumacker, H. B., Jr., Reheri, A,, Boone, R. D. and Kajikuri, H.: Ventricular Fibrilla-tion in the Hypothermic State. P a r t IV, A n n . of Surgery, 143:2:223 (Feb.) 1956. 24. Scheinberg, P. and, Stead, E. A,, Jr.: The Cerebral Blood Flow in Male Subjects asMeasured by the Nitrous Oxlde Techni ue J Clin. Investigation, 28:1163-1171, 1949. 25. Kety, S. S. and Schmidt, C. %.; The Nitrous Oxide Method for the Quantitative Deter-mination of Cerebral Blood Floow in Man. J . Clin. Investiation, 37 :476-483, 1948. 583