Moderate hypothermia

The Utilization of Moderate Hypothermia as an Adjunct to 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< SU R G I CAI P R 0 C ED U IR E S on poor - r i s k 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 to be a valuable adjunct in this regard. Sixty cases representing a variety of major dissbilities and requiring extensive surgical procedures have been operated upon with this technique with encouraging results.

It is the purpose of this paper to describe our technique of hypothermia, to discuss the rationale for its use in extensive surgical procedures, and to record some of our observations.

Technique HAKBITUKATE is given to the patient a t bedtime the eve- 9 ning before the operation is scheduled. No other premedication

is administered.

General anesthesia is induced with 2.5 per cent Petitothal sodium,@ after which the patient is taken into the operating room and placed tipon a water-cooled mattress. Electrocardiograph electrodes are placed on all extremities and connected to a Cambridge Cardio- scope. ERG recordings are made intermittently by a direct scriher electrocardiograph attached to 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 to the infusion system with appro- priate stopcocks so that they may be administered as desired.

Temperatures are recorded by a T,eeds & Northrop temperature recording machine from a thermocouple lead placled in the rectum, or in the esophagus, depending on the site of the operation. Readings are also made directly with a Telethermometer.

*Presented before the Thirtieth Congress of Anesthetists, Arlnual Meeting of tlic Members u f thc International 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. General Hospital, 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- ant (d-tubocurarine) is administered. A cuffed endotracheal tube is inserted under direct vision. A mixture of 50 per cent nitrous oxide and 50 per cent oxygen with intermittent vaporization of ether is administered in a semi-closed system. The patient’s respiration is assisted or controlled by a Blease Pneumoflator, which is a mechani- cal respirator. This respirator has a 5 cm. water negative pressure phase. The respiratory rate is regulated a t 16-20 per minute. The positive pressure phase is regulated to deliver a tidal volume of

The cooling of the patient is started by circulating ice water through the mattress with a Thermorite unit. In addition to the mattress, ice bags are placed on the anterior surface of the body.

Cooling is facilitated by intermittent administration of Arfonad to avoid reflex vasoconstriction. The systolic blood pressure is maintained a t 10-40 mm. of Hg below the initial level. Arfonad is not necessary if there has been a fall in the systolic blood pressure following 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.

400 - 600 CC.

TARLE 1 Operative Procedures

Thoracotomies 17 No. of Cases

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

Thyroidectomy for loxic goiter 2

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

Radical hysterectomies (Wertheim) 10 Hysterectomy-gas gangrene 1 Abdominal perineal resection of rectum

Neck

Abdominal

Pelvic I S

4 Total No. of Cases 60

2

26

571

Albert, Spencer, Ecclston, Shibuya, Albert and Thistlethwaite

Shivering cannot be eliminated by ganglioplegic drugs unless there is a concomittant depression of the central nervous system.

In approximately 30 - 60 minutes the rectal temperature will have fallen to 35 - 34 degrees C. When this temperaturie is reached the ice bags are removed. The patient is then positioned and the operation is started.

The circulation of the ice water in the mattress is interrupted when rectal temperature reaches 33" C. The patient's temperature is maintained between 32-30" C by varying the temperature of the water circulating in the mattress.

The systolic blood pressure is maintained at a level above 90 inin. Hg. If the blood pressure falls below this level the patient is placed in moderate Trendelenburg position. If further support is necessary, Neo-synephrine 20 tng. per 500 cc. infusion is started.

Whenever signs of ventricular irritability or cardiac arrythmias are seen on the cardioscope screen, the Arfonad infusion is started regardless of the level of the blood pressure. As :;eon as the cardiac rhythm reverts to normal the infusion is stopped. The Neo-synephrine infusion is begun when necessary to combat the hypotensive effect of the Arfonad.

Rewarming of the patient is accomplished by circulating warm water through the mattress. When the temperature reaches 33" C. the patient is transferred to the recovery room. All patients are awake a t the termination of the surgical procedure.

Report of Cases and Observations I X T Y P A T I E N T S have been operated upon with moderate hypo- S thermia as an adjunct to general anesthesia. Tihis report does not

include patients with cranial1 or intracardiac operations. A wide variety of surgical procedures is represented in this group of sixty patients, and the different operative procedures are listed in table 1.

- TABLE 2

Age Distribution of Cnscs

Age No. of Cases P e r cent Group per cent Under 4 weeks 1 3.3 10-20 years 3.3 21-29 years 30-39 40-49 50-59 60-69 70-79

5.0 30.0 15.0 13.3 20.0

3.3

11.7

45.0

80.90 4 6.7 43.3

5 i 2


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

The ages of these patients ranged from 6 hours to 89 years (see table 2 ) . Twenty-six were classified as poor-risk patients, either because of their particular existent disease, or because of their seripus cardiovascular or renal disease. Twenty-six were classified a s fair- risk patients. Most of the patients in this group had pulmonary tuberculosis or malignant diseases. Eight patients were classified as good risks. Twenty-six patients had evidence of cardiac disease, of which twelve had EKG evidence of coronary insufficiency (table 3 ) .

There were no serious complications attributable to the hypothermia or to the anesthesia. There was only one instance of ventricular fibrillation. This developed in association with a serious blood 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. Two of these deaths occurred after esophageal resections, one death occurred from a leaking suture line following a repair of a tracheo- esophageal fistula, and the fourth death was due to hepatic coma following a portocaval anastomosis (table 4).

It is striking to notice how hypothermia reduced the amount of anesthetic agents required by the patients.2 On the average, only about one-half of the expected amount of Pentothal and ether was necessary to maintain a satisfactory level of anesthesia. Table 2 shows the comparison of the average amount of Pentothal and ether required for 10 patients who had operations for radical hysterectomies, and 10 patients who had operations for gastric resections with a similar number of patients undergoing the same procedures without hypothermia (table 51.

TABLE 4 Mortality During First Week Post Surgery

Age Case Time of Death Cause

16 yrs. Resection patent ductus I n 0. R. Bleeding 49 yrs. Gastric exploration 1 hour p. 0. Bleeding 58 yrs. Esophageal resection 24 hours p . 0. Cardiac failure

6 hours Broncho esophageal fistula 3 days p. 0. Midiastinitis

5 5 YTS. Esophageal resection 4 days p. 0. Cardiac Failure

31 yrs. Porta caval shunt 5 days p. 0. Hepatic coma

573


TABLE 5 Radical Hysterrctomirs

Comparison of Two Grasps of Casrs Hypothermia With Without

Number of cases 10 10

Duration of anesthesia in hrs. Pentothal in mgms. Ether in C.C.

Curare in mgms. Recovery time in hrs.

5 $4 750

75 20

I n 0. R.

5 1250

140

30 1:: hrs

Urine output in first 24 hrs. 2100 C.C. 750 cc.

Gastric Resections Comparison of Two Groiips of Cascs

Hypotherniia With Without

Number of cases 10 10 Duration of anesthesia in hrs. 4 3 Pentothal in mgms. 800 1.300

Recovery time in hrs. I n 0. R. 1 y; Ether in cc. 80 160

Urine output in first 24 hrs. 1800 c.c 700 c.c

From the anesthesiologist's point of view the patients are easier to manage with these reduced amounts of anesthetic agents. Minimal amounts of these anesthetic agents are required to maintain the patient in the proper anesthetic level for adequate relaxation. There is little fluctuation in systolic blood pressure throughout the procedure since the hypotension resulting from a too deep level of anesthesia can be avoided.

In addition, hypothermia protects the central nervous system during periods of hypotension and aiioxemia. Prolonged periods with the systolic blood pressure below 90 mm. Hg are tolerated without ill effect.

Twenty-seven patients, or nearly half of the total number, demon- strated myocardial irritability during the cooling process. Arrythmias with premature ventricular contractions were the most constant changes (table 4) . I n all instances normal cardiac rhythm was promptly established by start ing the infusion of Arfonad.

TABLE 6 Temperaturr Variations

Incidence of Myocardial Irritability Average temperature 30-31" C

Variations between 28-33.5"C E.C.G. changes during cooling 28 Patients

Temperatures a t which E.C.G. occurred 3 5 ~ 3 1 ~ C controlled with Arfonad

574


Patients operated upon under hypothermia have less adrenocortical response than is expected for patients having similar procedures without h y p ~ t h e r m i a . ~ They are alert and awake almost immediately after the completion of the operation, and they seldom have the typical “knocked out” appearance which the average patient demonstrates after a major procedure. They tend to excrete rather than to retain water and sodium as one might expect5 A urinary output of 1500-2000 cc. in the first 24 hours is not unusual. Atten- tion to fluid replacement is necessary during the early postoperative period. Before the authors were acquainted with this post-hypothermia diuresis with a loss of sodium, two patients developed salt depletion syndromes. These two patients had received postoperative fluids in the usual manner, with saline solutions being avoided during the first 48 hours (table 5 ) .

Details of this altered corticoid response in these cases is t o be published a t a later date. Studies have been made of the water and the electrolyte metabolism, the steroid levels in the blood and the urine, and the serial blood and plasma volume determinations.*

Discussion P A T I E N T UNDERGOING an extensive surgical procedure is 31 subjected to considerable trauma and stress from which he has

to recover in order to make the surgical intervention a success. In order to minimize the role of anesthesia as a stress stimulus6 attempts have been made to administer a combination of drugs, each acting on a part of the nervous system in order to obtain the desired hypnosis, analgesia and relaxation? A t best there still remains significant stress due to anesthesia. Since hypothermia reduces the amounts of the general anesthetic agents required, and, in addition, produces a physiologic depression of tissue metabolism, it will reduce the stress of anesthesia.

Because all of the body enzymes act a t an optimum temperature, the reduction of body temperature will result in depressing the enzymatic action. Metabolism of all the organs and systems of the body is thus reduced. This reduced metabolism with reference to the brain will dull the sensorium; hence, the amounts of anesthetic agents needed will be lessened.R

Normally the brain cannot withstand an oxygen deficit; it is dependent entirely on the minute to minute blood flow for its oxygen supply. If the circulation is interrupted for more than a few minutes irreversible damage to the brain cells ensues. Whenever hypotension occurs, either due to blood loss, hypotension intentionally induced by ganglioplegic agents, or from deep levels of anesthesia, physiological adaptations 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.

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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 68.0

supply to the central nervous system. These changes are either an increase in the rate of blood flow to the brain, due to the lowered cerebral vascular resistence, or are due to increases in the arterial- venous oxygen difference of the cerebral circulation (table 8) . In spite of the adaptations, the cerebral cortex is on the verge of ischemia.ll l2

The only way to protect the brain from ischemia during hypotension is to reduce the oxygen requirement of the brain. The central nervous system depressants will reduce the cerebral metabolic rate only to a limited extent. A physiologic way to reduce the oxygen requirement of the central nervous system is to reduce the body temperature. Moderate hypothermia ranging between 32 - 30" C. reduces the cerebral metabolic rate an average of 50 - 75 per cent.13 Appar- ently there is no linear proportion between the degree of cooling and the reduction of the cerebral metabolic rate in man14 (table 8).

Marked reduction in the cerebral metabolic rate has been observed with a reduction of 1 C. in the body temperature. The cerebral metabolic rate decreased 50 per cent or more by the time the body temperature reached 30" C. in all of the individuals studied. In all instances there was a marked increase in the cerebral vascular resist- ance in spite of hypotensive levels of blood pressure which were produced by vasodilator agents. With this reduction in the rate of blood flow there is only a small variation in the arterio-venous oxygen difference ; thus, the cerebral metabolism is depressed almost proportionately to the reduction of the blood flow. Studies of cerebral metabolism have been made utilizing Thorazine,@ Arfonad, alcohol and Pentothal at levels of blood concentration equivalent t o those found in patients under hypothermia. The results have been shown that these drugs used alone or in conjunction with each other had little if any effect on the cerebral metabolic rate. Therefore it is concluded that the reduction in cerebral metabolism observed under hypothermia is due entirely to the effect of hypothermia rather than to any drug or combination of drugs used.15 l6 l7 Nevertheless, one should be cautioned against hypotension due to excessive blood loss. As seen in table 7, the cerebral blood flow is markedly reduced in patients with hypothermia. This coupled with a deficient blood volume may cause a severe ischemia with irreversible damage to the central nervous system.

The protective effect of lowered cerebral metabolic rate under hypothermia is clinically substantiated by several instances in which

577


patients have been allowed to remain in a state of hypotension with a systolic blood pressure of 50 mm. Hg for periods of 30 - 45 minutes without untoward effects.

Recently we were called upon to consult on a most interesting- case* which dramatically verifies this protective effect of hypotherniia on the brain. A two weeks old infant was left on a door step during one of Washington's coldest spells. The infant was picked up by the hospital ambulance and brought to the emergency ro'om. No heart beat was heard by several o>bservers, no pulse was felt, and the infant was pronounced dead. After being in the warin environment for over 30 minutes the infant was noted to gasp. The heart beat could be faintly detected. Rewarming of the infant was continued. The rectal temperature was taken with a Teletherinonieter about an hour later and it registered 20" C. V17ith complete rewarming the infant recovered. I t appears that the severe degree of hypotherniia had completely protected the infants' central nervous system so that a prolonged period of cardiac standstill was tolerated.

The development of cardiac arrhythmias, which may lead to ventricular fibrillation, has been the biggest deterrent to the use of hypothermia. In order to combat this possible complication, attempts have been made to reduce myocardial work load and myocardial irritability by utilizing certain drugs.

It has been the impression of many investigators that there exists a critical tem,perature range (29" -25" C.) in which myocardial irritability is most prone to occur.1s In Contrary to this, we have found that premature ventricular contractions and signs of myocardial irritability may occur a t any stage of ?he cooling, especially in the poor-risk and the elderly patient. W e encountered this phenomenon with cooling of 1" C.

Our experience with drugs used in an attempt to control myocardial irritability has been most encouraging. Two drugs, Thora- zine** and Arfonad, have been utilized. The former drug has been shown to have antifibrillatory properties in dogs.20 21 22 Both of these 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 two properties make them of value in controlling arrhythmias, and, in addition, facilitate cooling by their vasodilation effect during hypothermia. Thorazine has two distinct disadvantages in this respect. The first is that the induced hypotension cannot be controlled ant1 cannot 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


Fig. I

Fig. 2

579


this drug, On the other hand, Arfonad has neither of these properties. There is no tachycardia, and the hypotensive effect can be controlled easily and reverted by the administration of Neo-syiiephrine or other vasoconstrictor agents without distracting in the least from its effect of controlling arrhythmias and myocardial irritability.

Our observations in this group of cases indicate that Arfonad has a direct action on the myocardium. W e have observed arryhthmias which develop in the hypothermic state while the patient is already in hypotension due to the effect of the anesthetic agent administered. Normal cardiac rhythm is restored when Arfonad is administered.

Fig. 4

580


Fig. 5

Fig. 6

There was no further fall in blood pressure. One can attribute the effect directly as an action on the myocardial tissue, rather than an effect of Arfonad on the peripheral vascular bed. Also, it is interesting to note that the arrhythmia did not recur when the blood pressure was raised or maintained with Neo-synephrine infusion, and the work load on the heart was increased. The effect of Arfonad on the myo-

581


cardium seems to persist for a period of 1 - ’2 hows. Occasionally we noted a recurrence of myocardial hyperirritability which was in turn again controlled by instilling the Arfonad infusion. These beneficial effects of Arfonad have been documented several times with continu- ous EKG tracings during the operative procedure showing reversals of arrhythmias to normal rhythms (fig. 3 , 2, 3, 3, 5 , 6).

Summary YPOTHERMIA APPEARS to be a valua.bIe adjunct to general anesthesia for patients undergoing extensive surgical

procedures. Hypothermia diminishes the stress of the anesthetic agents administered and, in addition, seems to alter a patient’s normal reaction to the stress of surgery.

The technique for indacing hypothermia is briefly presented.

A series of sixty patients receiving hypothermia is reported.

The protecting effect of hypothermia on the cerebral cortex for tolerance of hypotension and reduced blood flow has been discussed.

Arfonad has been shown to be an effective agent for the control of 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 Report

on 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 of Hypothermia 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 arid Ischemia in Man and Dog. Presented at the National Academy of Siciences, Natronal Research Council, 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. Par t 1. Ann. of Surg.. 141 :145, 1955.

7. Hune D. M.: Effect of Hynothermia on Adrenocortical Secretion in Animals. Presented at 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 and

Alcohol on Cerebral Hemodynamics and Metabolism. Am. 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 :125 137 (Jan.) 1950.

14. Albert, S. N. and Fazekas, J. F.; Cerebral Hemodynamics and Metabolism During Induced 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. Par 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 in Hypothermic 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.


19 Covins B. G Charleson, D. A. and D’amato, H. E.: Ventricular Fibrillation in Hypo- thermid Dog. Ad. I. Pi js io logy , 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 Sympathomimetic Amines. 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. Par t IV, Ann. of Surgery, 143:2:223 (Feb.) 1956.

24. Scheinberg, P. and, Stead, E. A,, Jr.: The Cerebral Blood Flow in Male Subjects as Measured 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.

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Health & Medicine

Moderate hypothermia