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Induced Hypothermia in Neurologic Conditions
Induced Hypothermia in Neurologic Conditions ALFRED UIHLEIN, M.D. HOWARD R. TERRY, JR., M.D. JOHN T. MARTIN, M.D.
THE use of induced hypothermia as an adjunct to neurosurgical techniques and to the treatment of certain neurologic conditions prompts both speculation and hope. Many physiologic problems remain to be solved; however, one easily may anticipate the time when neurosurgical procedures can be accomplished with the help of the relatively bloodless fIeld now familiar to the cardiac surgeon. Our purpose is to review briefly the physiologic data now assembled concerning induced hypothermia2 , 7,21-23, 30, 41, 44, 45 and to present our experience with a series of neurosurgical patients on whom this technique was used. The use of cooling as an analgesic agent probably predates medicine as a science, for the injured part was frequently placed in cold water to relieve pain or inflammation. In the 1930's, Fay and Fay and Smith maintained the human body for days at temperatures between 25° and 30° C. to allay the pain associated with inoperable carcinoma. Later, Crossman and AlIen were instrumental in introducing refrigeration as an anesthetic agent in amputations for gangrene. Pratt and Collins found this method satisfactory, and others10 have reported similar successes. Pontius and DeBakey have shown experimentally that the brain withstands hypothermia well. A number of investigators 4, 6, 9, 26, 39, 40 have shown that the body's metabolic requirements can be decreased by hypothermia 2, 4, 29 and that the oxygen demand is decreased by lowered temperatures ;12, 18 therefore, it was considered that essential circulation to certain parts of the body could be interrupted safely for longer periods of time with refrigeration than without. 8 , 27, 31, 32, 38 Further experimental work by cardiac surgical research teams demonstrated that induced hypothermia consistently reduces the oxygen consumption of tissues proportionate to the degree of lowered temperature,13 if shivering is prevented, and that, as the temperature is dropped, the blood pressure becomes lowered, the pulse rate reduced and the respiratory rate slowed. 87
1079
1080
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
PHYSIOLOGY
Central Nervous System
Under normothermic conditions, cerebral ischemia produces a rapid and profound insult to the brain. Many reports attest to the speed with which flattening occurs in electroencephalographic tracings following cerebral circulatory arrest. 28 Vandewater and associates achieved occlusion times of 15 minutes and 10 seconds with both carotid and both vertebral arteries at 26.60 C. (79.8 0 F.) in one patient, and occlusion of both carotid arteries for 15 minutes at 26.50 C. (79.7 0 F.) in another patient without neurologic sequelae resulting from the occlusion in either instance. This represents a significant protection afforded by hypothermia that aids in the surgical treatment of vascular malformations or highly vascular tumors. Rosomoff and Holaday found an increase in cerebral vascular resistance and a reduction in cerebral blood flow in dogs under hypothermia. This reduction in cerebral blood flow was associated with an unchanged arteriovenous oxygen difference; therefore, the cerebral metabolic rate must decrease with a fall in temperature. Eckenhoff stated that this is a linear relationship down to an oxygen consumption of 50 per cent at 250 C. In hypothermic dogs, Rosomoff and Gilbert have noted a 4 per cent decrease in the bulk of the brain and a 31 per cent increase in the extracerebral intracranial space, the so-called slack brain, as well as a decrease in venous pressure and the pressure of cerebrospinal fluid. These pressures were greatly increased with shivering, however. Using three human volunteers, Stone's group confirmed these data and showed that shivering could increase oxygen demands from 76 per cent at 83 0 F. to more than 100 per cent without any change in temperature. Cardiovascular Effects
Hypothermia produces bradycardia of a degree almost directly related to the amount of decrease in temperature,14 This linear relationship does not apply to blood pressure. The electrocardiogram in hypothermia is affected by such factors as the blood oxygen and carbon dioxide pressures, the pH, and the electrolyte concentration. I9 In general, the usual changes associated with cooling to temperatures above 28 0 or 29 0 C. appear to be low-voltage or absent P waves, prolongation of the QRS and ST intervals, and inversion of the T waves. Fleming and Muir reported 29 cases in which hypothermia was used for cardiovascular surgery and confirmed the presence of a prolonged PR interval in many instances. Varying degrees of heart block and alterations of rhythm are more common with temperatures below 28 0 to 30 0 C., but warming the patient reverses these changes,15. 24
Induced Hypothermia in Neurologic Conditions
1081
Rose and co-workers cooled patients who did not have cardiovascular disease and measured cardiac output, stroke volume, mean arterial pressure, peripheral resistance, cardiac work, mean circulation time, central blood volume, and the percentage of packed cells (hematocrit). None of the changes were consistent or of statistical significance. The major hazard of hypothermia is vent:-icular fibrillation. However, in the absence of cooling below 28° or 29° C., or direct cardiac manipulation, electrolyte imbalance and hypoxia, the occurrence of ventricular fibrillation should be uncommon. Ventricular extrasystoles may be considered as precursors to fibrillation; when they are present, ventilation should be increased and partial or complete warming considered. Since neurosurgery does not require cardiac manipulation, some of the adverse effects of hypothermia on cardiac rhythm associated with cardiac surgery do not apply. Should fibrillation occur, prompt thoracotomy and cardiac massage are indicated to restore rhythm and perfusioll unless cooling is being done internally by a pump-oxygenator. Adequate treatment of ventricular fibrillation under hypothermic conditions may be difficult. METHODS OF ACHIEVING HYPOTHERMIA
Induced hypothermia requires that the homeothermal controls and heat-production mechanisms of constant-temperatured man be overcome. ll Thereafter, any decrease in environmental temperature will be reflected in loss of heat from the body. Many drugs have been used to facilitate cooling. Currently, general anesthesia has almost completely replaced the "lytic cocktail" as a means of obtunding the homeothermal regulators of the central nervous system. 22 • 30 Shivering can be controlled with relaxants, by the use of deeper levels of anesthesia, or by the intravenous injection of chlorpromazine or promethazine (Phenergan). The application of cold then effects a lowering of body temperature to the desired levels. Methods of cooling vary widely.7. 36 For simplicity, one might modify the classification of Eckenhoff as follows: A.
EXTERNAL SURFACE COOLING
1. Immersion in water. An anesthetized patient is placed in a whole-body
water bath and ice is added. This inexpensive method produces a rapid decrease in temperature. 2. Cooling blankets (Davol, Therm-O-Rite, etc.). An anesthetized patient is placed between blankets containing imbedded coils through which a coolant solution flows either by gravity or from a heater-cooler pump unit. This gives slow cooling and warming with more control than does the ice bath but it is more costly in time and equipment. 3. Forced-air units (Autohypotherm refrigeration bed).6 These units force large volumes of cooled or warmed air around the patient in a tight en-
1082
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
closure. They are relatively new, are not widely employed in the United States, and are rather expensive. 4. Direct application of ice bags, coolant bags or cracked ice. This method may be used alone or to supplement use of the mattresses. 5. Suspension of the body in a deep-free.ze unit. B.
INTERNAL SURFACE COOLING
1. Circulation through a stomach balloon. 2. I cc-water enema. 3. Cold saline solutions poured into the thorax or abdomen, or packed about the aorta. C. INTERNAL VASCULAR COOLING (PUMP-OXYGENATOR)
This requires removal of blood, cooling it by heat exchangers, and restoring it to the circulation, with or without the use of an extra pump or an oxygenator. This can be an extremely rapid form of cooling, especially if it is associated with extracorporeal circulation. CLINICAL DATA
Since 1955, induced hypothermia has been used in various aspects of an active neurosurgical service at the Mayo Clinic (Table 1). It has been employed therapeutically as early as possible after admission to the hospital in 20 cases of acute head injuries to combat coma, extensor spasm, decerebrate rigidity, opisthotonus and hyperpyrexia. Fourteen of these patients survived and six died. The results have been gratifying in some instances and disappointing in others; the over-all picture suggests that this form of treatment may be lifesaving and should be considered. We have been well satisfied with the use of blankets for cooling these patients, because it reduces nursing care and permits a more accurate control of hypothermia. In one patient, hypothermia was maintained for as long as a week, the rectal temperature being maintained at about 33 0 C. (91 0 F.), with complete recovery from a severe neurologic defic:t. Table 1.
Hypothermia in Neurosurgery: 51 Cases
CONDITION
Berry aneurysms ... " ......... . Brain tumors. . . . . . . . . . . . . . . . . .. . .. . Meningiomas. . . . . . . . . . . . . . ....... . Gliomas .............. . Craniopharyngioma ............... . Hemangioma ........ . Head injuries ........... . Postoperative ............... . TOTAL . . . . . . . . . . . . . . . . . . . . . . . . .
CASES
3 3
1 1
24 8
20 9
61
Induced Hypothermia in Neurologic Conditions
1083
We have used induced hypothermia in the treatment of nine patients with postoperative complications manifested by progressive stupor, hyperpyrexia and cerebral edema in patients operated on for parasellar lesions encroaching on the hypothalamus, for subdural hematomas and for brain abscesses. The dramatic recovery in seven of nine such patients who had failed to improve with the usual therapeutic efforts was impressive enough to justify its further application. In these patients, the rectal temperature was not decreased to less than 33 0 C. (91 0 F.), as a rule. Varying degrees of shivering were noted, and it was difficult to control shivering below this temperature. We have employed induced hypothermia in the surgical attack on intracranial vascular tumors, aneurysms of the circle of Willis, arteriovenous malformations, and certain brain tumors. Experience with the use of induced hypothermia in the treatment of any of these conditions is necessarily limited, except possibly in the case of bleeding intracranial aneurysms, so that long-term follow-up studies must be conducted before we know whether induced hypothermia has improved the surgical attack as well as the clinical results. BRAIN TUMORS
Eight patients with brain tumors were selected for treatment with induced hypothermia. The lesions included three recurrent hemispheric gliomas, three meningiomas, an intracerebral hemangioma and a craniopharyngioma. Two postoperative failures were noted. One patient with a recurrent glioma died of hemispheric infarction and cerebral edema. In the other patient, a large meningioma of the sphenoid ridge was resected, with severe loss of blood; in addition, there was severe cerebral edema with hypertension, for which large amounts of trimethaphan camphorsulfonate (Arfonad) were administered. It was thought that a combination of factors was responsible for this patient's death, namely hypothermia of 29° C. for 11 hours, excessive loss of blood, although the loss was adequately replaced, and large doses of a hypotensive drug. Extensive renal damage was found at necropsy. The other six patients responded well to hypothermia and recovered uneventfully. The "slack brain" reported with vascular lesions is not so apparent with brain tumors in our experience; capillary oozing appears to be lessened and the postoperative recovery period is shorter than with conventional types of anesthesia. INTRACRANIAL ANEURYSMS
A total of 24 verified intracranial aneurysms have been operated on at the Clinic in patients under induced hypothermia, the temperatures
1084
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
Fig. 1. Equipment used for induced hypothermia. The Therm-O-Rite blanket is on the table, with the refrigeration unit and oscilloscope on the right, and the inhalation anesthesia unit on the left.
ranging between 27° C. and 31 ° C. The Therm-O-Rite blanket waEl used in each instance to cool and then warm the patient (Fig. 1); General anesthesia always was used and respirations were controlled. A malleable spinal-puncture needle was inserted into the lumbar subarachnoid space in some patients to remove cerebrospinal fluid when required. This procedure cannot be used when the patient is immersed in ice water to induce hypothermia. Surgical exposure of the carotid and vertebral arteries is carried out when indicatedl while the temperature is being lowered, followed by craniotomy. The aneurysm is exposed when the desired level of hypothermia is attained. To prevent serious hemorrhage at the time of exposure of the aneurysm, the carotid and vertebral arteries can be occluded by tapes or a hydraulic clamp48 for varying periods, or the afferent intracranial artery can be occluded temporarily by means of an Olivecrona, a Mayfield or a Schwartz clip after the vessel wall is covered with a pad of cotton soaked in a 2.5 per cent solution of papaverine.20 • aa After aneurysmal repair, the temporary occlusive device is removed. In our opinion, the postoperative neurologic deficit is less than that resulting from similar procedures carried out under normothermic conditions. Warming of the patient is begun I1S soon as the definitive operation is accomplished by increasing the temperature of the circulating solution in the blanket to 43° C. (110° F.). Gradual warming prevents burning of the skin and permits the surgeon to check hemostasis before closure
Induced Hypothermia in Neurologic Conditions
1085
of the wound. The patient frequently responds to verbal commands when his body temperature reaches 330 C. (91 0 F.) and his vital signs are stabilized. One patient whose temperature was 300 C. (86 0 F.) asked for hot soup when he arrived on the ward. Should compensatory hyperpyrexia develop in the early postoperative period, it can be controlled by the use of one half of the refrigeration blanket. Selection of Patients
Our policy has been to perform bilateral carotid angiography as soon as the patient's condition warrants the procedure and to operate on the verified aneurysm when the time appears most propitious. The site and size of the aneurysm, the presence of an intracranial clot, the presence of arterial spasm, the age of the patient and the severity of the neurologic deficit are all factors that haye been considered in the selection of our patients for induced hypothermia. The policy for selection is arbitrary and is left to the discretion of the surgeon in charge of each patient. To analyze our selection, the patients were grouped into four grades with regard to operative risk. Grade 1 indicates a patient who is conscious, with or without a significant neurologic deficit and with or without blood in the subarachnoid space. Grade 2 represents a drowsy patient with some neurologic deficit but who is stabilized. Grade 3 represents a drowsy patient with a definite neurologic deficit, retinal hemorrhage and early papilledema. Grade 4 indicates a deteriorating patient who is nearly moribund, with a major neurologic deficit, grossly bloody cerebrospinal fluid, hypertension and severe nuchal rigidity. The results of the surgical treatment with induced hypothermia were classified into four categories. "Excellent" means the patient is well, with no neurologic deficit; "good" means a patient who is well and working but who has a minimal neurologic deficit; "fair" indicates some aphasia and hemiparesis; "poor" indicates a major neurologic deficit, with no improvement over the preoperative condition or a state that is even worse. All the patients were selected for induced hypothermia because, in the opinion of the surgeon, this method appeared to offer more protection to the patient under the given circumstances. Hypothermia was selected in several instances because the presence of degenerative vascular changes was suspected as the result of angiography. During the same period, 82 patients with intracranial aneurysms were treated surgically without hypothermia; of this group, 47 had craniotomy and an additional 18 had craniotomy with carotid ligation. Aneurysms in various locations were operated on with the aid of induced hypothermia. We have analyzed the techniques used and the surgical results in each instance, according to the location of the aneurysm. The estimated preoperative risk of the patients, their age and the number
1086
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
of days from the last subarachnoid hemorrhage, along with the postoperative results, also were studied and will be presented in another publication. 43 The number of patients admittedly is small, but the results obtained under the circumstances appear to justify further use of this technique in selected instances. We do not wish to advocate that every patient with a bleeding aneurysm should be subjected to induced hypothermia. However, if it may be necessary to interrupt temporarily the arterial supply to the brain or a segment thereof, this can be accomplished with less danger of a serious neurologic deficit under induced hypothermia than under normothermic conditions. As others have reported,3. 20. 26, 33, 34 the best surgical results are anticipated in patients whose operative risk is graded 1 or 2. However, five of our patients in the grade 3 category of operative risk made gratifying recoveries. No patient whose operative risk was graded 4 recovered, even with hypothermia; however, all such patients were operated on in desperation. In two of these patients, the internal carotid artery tore as a clip was applied, necessitating permanent ligation, with subsequent cerebral infarction. Another patient whose risk was graded 4 was subjected to a second attack on an aneurysm of the anterior communicating artery under hypothermia and died of meningitis on the tenth postoperative day. This was a surgical triumph but the patient died. Definitive treatment of aneurysms under hypothermia demonstrates that major vessels can be occluded for relatively long periods without. appreciably altering the postoperative results. The singular advant.age of temporary occlusion of the afferent artery proximal to the aneurysm (designated as "clip min." in the tables) apparently merits its use in the treatment of aneurysms of the middle cerebral artery and those of the anterior cerebral-anterior communicating arteries. This technique appears to be more practical than does temporary occlusion of both carotid arteries in the neck, along with the vertebral arteries. l A vasodilator, such as a 2.5 per cent solution of papaverine, should be applied to the wall of the artery before the temporary clip is applied. 20 • 25, 33 Under normothermic conditions, this technique probably would not be so successful. Results
INTERNAL CAIW'l'ID ARTEHY. Aneurysms of the internal carotid artery were divided into those in the region of the posterior communicating artery and those in the region of the carotid bifurcation (Table 2). Five patients with the former type of lesion and one with the latter type were operated on under hypothermia. All patients represented grade 1 or 2 operative risks except one, in whom the risk was graded as 4. The one patient whose aneurysm was near the bifurcation was operated Oll
Induced Hypothermia in Neurologic Conditions Table 2. AGE (yr.) PREOP. AND SIDE HISK
1087
Hypothermia in Cerebral Aneurysms
DAYS FROM BLEEDING TO OPERATION
CLIP OH MUSC.
CLIP
(min.)
PAPAV- TEMP. ERINE (QC.)
RESULT
(2.5%)
Internal carotid near posterior communicating 47 L+R 52 R 59 R 55 R 64 L
43
1+ (mult.) 2 2 2 4
21 53 10*
C (R)
0
No
C
1.5
Yes
M C C
0 0 0
No No No
30 Excellent; 3rd nerve improved 29 Good; resid. hemiparesis 29 Good 29 Excellent 29 Died
Anterior cerebral 46R 61 R
3
10* 15 C (subdural) 24 11 C+M 0
Yes
29
Excellent
No
30 Excellent; facetious
Internal carotid near bifurcation 25 L
2
9*
M
t
No
29
Good; dysphasia
* Hematoma present.
t 9 minutes RCC; permanent on LCC.
nine days after her last hemorrhage, with good results. None of the patients with posterior communicating aneurysms were operated on less than ten days after the last hemorrhage. Of these, the one with the grade 4 risk died shortly after operation, while the remainder were improved. ANTERIOH CEREBRAL ARTERY. Two patients who had aneurysms of the anterior cerebral artery proximal to the anterior communicating artery were operated on, with excellent results (Table 2). In both instances, the aneurysms were clipped. One patient had a contralateral subdural hematoma in the parietal region that was evacuated first; two weeks later, the aneurysm of the right anterior cerebral artery was attacked after the anterior cerebral artery on either side of the aneurysm was occluded by means of Schwartz' clips for 15 minutes before clipping the neck of the aneurysm. MIDDLE CEREBRAL AH'l'ERY. Nine patients with aneurysms of the middle cerebral artery near the trifurcation were operated on under hypothermia without a death (Table 3). Five patients had massive intracerebral clots. One patient was unimproved. Aneurysmorrhaphy was
1088
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
Frontal
\
\
Ane1.:1~"\jsm.
opened
.
Fig. 2. Aneurysm of right middle cerebral artery: View at operation, showing the temporary clip on the middle cerebral artery, aneurysmorrhaphy, and ligation of the neck of the aneurysm. Table 3.
Hypothermia in Cerebral Aneurysms: Middle Cerebral Artery N ear Trifurcation
AGE (yr.) PREOP. AND SIDE RISK
DAYS FROM CLIP BLEEDING TO OR OPERATION MUSC.
CLIP
(min.)
PAPAV- TE:\(P. ERINE (OC.)
(2.5%)
36R 43R
3
1
90 8*
M
t
7 15.5
No Yes
48L 31 L
3 3
22 14*
C C
0 9
No Yes
40L
2
23
M
0
No
22L
2
6*
C
8.5
Yes
27L 50R 43 L
2 1 1
8 yr.* 17 29*
t
9.5 12 24
Yes No No
C C+M
RESULT
Excellent; focal seiz. Good; minimal field defect 29.5 Good; apraxia 30 Good; resid. mild aphasia 31 Unimp.; hemipl., aphasia. field def. 29 Good; minimal aphasia 30 Ex('Pl1ent 29 Excellent 28.5 Excl'llent; min. dysphasia 28 28
• Hematoma present. t Aneurysmorrhaphy.
carried out with excellent or good results in two patients who had large aneurysms after temporary clipping of the middle cerebral artery proximal to the aneurysm (Figs. 2 and 3). These results represent a surgical triumph because of the size of the aneurysm and the radical approach,
Induced Hypothermia in Neurologic Conditions
1089
Fig. 3. Large aneurysm (arrows) of left middle cerebral artery near trifurcation, demonstrating elevation and mesial displacement of middle cerebral artery by intracerebral mass lesion. Table 4.
Hypothermia in Cerebral Aneurysms: Anterior Cerebral-Anterior Communicating Arteries
AGE (yr.) PREOP. AND SIDE RISK
DAYS FROM CLIP BLEEDING TO OR OPERATION MUSC.
46R
4
9
63 L
3 2
44L 62 R 52R 51 L 42R
3-4
1 1 4
CLIP
(min.)
PAPAVTEMP. ERlNE
(2.5%)
C
5
Yes
28
C+M
1
Yes
8 13* 10 17 7*
C M M C C
5 0 0 0 5
Yes No No No Yes
(OC.)
RESULT
28 Died 13 days p. 0 . , meningitis 31 Died at home, 1 mo.; recur. hem. 28 Excellent 30 Unimproved 30 Excellent 31 Excellent 29 Died
* Hematoma present.
with minimal sequelae. Without hypothermia, this operation would not have appeared practical. Varying periods of occlusion were used; the longest period was 24 minutes and was followed by excellent results. ANTERIOR CEREBRAL-ANTERIOR COMMUNICATING ARTERIES. Seven patients with aneurysms at the juncture of the anterior communicating and anterior cerebral arteries were operated on (Table 4). Only one had an intracerebral clot; this patient represented a grade 4 operative risk and died after operation. The two other surgical deaths in this group were mentioned earlier. The remainder of these patients survived their direct surgical attack. One of these died at home one month later of recurrent hemorrhage when the Olivecrona clip came off. The other three patients had an excellent postoperative recovery.
1090
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN November 25
27
26 In blalnket
106 104 ~ 102
::.
.... 100 ~
~
~
~
98
.--
~
~
96 94 92
90 Intake·cc Output·cc
Cl
CO 2
1800-2000 850-960 93 18
NOv.23-lntra and extrasellor chromophobe adenoma removed
Fig. 4 (Case I). Control of hyperpyrexia by induced hypothermia after removal of pituitary turnor.
Illustrative Cases
The following cases are representative of the type of patient that was selected for induced hypothermia and demonstrate the need for further studies of this technique. The first case is an example in which hypothermia was used therapeutically in the early postoperative period, while the others illustrate the type of patient selected for induced hypothermia rather than for some other form of surgical approach. The therapeutic use of refrigeration was graphically illustrated in the two following patients. CASE 1. On the third day after uneventful removal of a chromophobe adenoma of the pituitary, a 57-year-old man experienced the development of pronounced edema of the face and the conjunctival and orbital structures, with hyperpyrexia, loss of consciousness, dilatation of the pupils and bilateral Babinski's signs. Despite use of the usual measures for combating edema and maintaining the electrolyte balance, the patient's condition continued to worsen. After 48 hours of refrigeration by blanket, gradual improvement occurred in this patient's convalescence from a relatively hopeless situation to complete recovery, although the body temperature never decreased below 98° F. (Fig. 4). CASE H. A 46-year-old man had a bleeding aneurysm of the anterior communicating artery that initially was wrapped with muscle without hypothermia, as it appeared to be hazardous at the time to apply a clip. He recovered satisfactorily for six months, when he had a recurrence of severe hemorrhage. He was admitted to our service in coma, with bilaterally dilated and fixed pupils, CheyneStokes respiration and bilateral extensor spasm. His condition appeared hope-
Induced Hypothermia in Neurologic Conditions January
1091
5
4
106r-----------,------------, 104 '»
102
(
In blanket
)
...::, 100 ~
~
~
Ob
98
~ 96
e
~
94
92 90 Urea Cl CO2
No
30 93 26 135
Dec. 6-Anterior communicating artery aneurysm wrapped with muscle
Fig. 5 (Case II). Induced preoperative hypothermia after acute subarachnoid hemorrhage.
Fig. 6 (Case II). Postoperative right carotid angiogram, showing persistence of aneurysm of anterior communicating artery. less. Pure blood was present in the cerebrospinal fluid. The patient was placed in the refrigeration blanket for 48 hours (Fig. 5.) The coma lessened graduallv. the extensor rigidity disappeared, pupillary responses returned, and the patient recovered sufficiently to permit angiography (Fig. 6) and re-exploration one week after his last hemorrhage. Re-exploration under induced hypothermia at 28 0 C. (820 F.) permitted evacuation of an intracerebral clot in the right frontal region that extended into the right lateral ventricle and filled it. A clot cast of the ventricle was aspirated. The aneurysm then was successfully clipped, sparing both anterior cerebral arteries. The patient's postoperative convalescence was most remarkable until the tenth postoperative day, when staphylococcic meningitis developed and he died. To survive massive intracerebral and intraventricular hemorrhage to a sufficient degree to permit reoperation appeared to justify
1092
ALFRED UIHLEIN, ROWARD TERRY, JR., JOHN MARTIN
Fig. 7 (Case Ill). Preoperative angiograms of aneurysm of anterior cerebral artery (arrows), showing shift of anterior cerebral vessels to right of midline by left parietal subdural hematoma. The lateral projection shows the elongated aneurysm, with forward compression of the sylvian vessels on the left by the subdural hematoma. the assumption that we would not have had a ~econd opportunity to attack his bleeding aneurysm without the early use of therapeutic refrigeration.
Induced hypothermia offers the surgeon certain allies in attacking bleeding intracranial aneurysms, as illustrated by the following case reports. CASE Ill. A 46-year-old woman was admitted to the hospital five days after the last of a series of three spontaneous subarachnoid hemorrhages, confirmed by the presence of blood in the cerebrospinal fluid, stiff neck and nausea. Angiography two days after admission revealed an aneurysm of the right anterior cerebral artery that filled via both systems, with a shift of the distal anterior cerebral complex to the right in the anteroposterior projection and forward compression of the left sylvian vessels in the lateral projection (Fig. 7). Left parietal craniotomy three days later uncovered a large subdural clot over the parietotemporal region that was evacuated. Two weeks later, under induced hypothermia at 29 0 C. (84 0 F.) for two hours, the aneurysm and both anterior cerebral arteries were exposed. The left anterior cerebral artery was smaller than the right, and cottonoid strips soaked in papaverine were applied. The right anterior cerebral artery was temporarily clipped with a Schwartz bulldog clamp for 15 minutes, while the neck of the aneurysm was tied with a black-silk ligature and an Olivecrona clip was placed over the decompressed aneurysmal sac. The Schwartz clamp then was removed. Recovery was excellent, and she returned to her secretarial position. An angiogram four months later showed no evidence of an aneurysm (Fig. 8). CASE IV. A 27-year-old robust man was admitted to the hospital in February, 1958. His first subarachnoid hemorrhage had occurred in November, 1950, with recovery. A convulsive disorder had developed in 1955. An angiogram elsewhere
Induced Hypothermia in Neurologic Conditions
1093
Fig. 8 (Case In). Postoperative angiogram, showing clip (arrow) at site of previous aneurysm.
Fig. 9 (Case IV). Preoperative angiograms, showing aneurysm ofleft middle cerebral artery. (See text for details.)
in October, 1956, had revealed an aneurysm of the left middle cerebral artery midway between the bifurcation of the carotid artery and the trifurcation of the middle cerebral artery. Repeat angiography elsewhere in January, 1958., had demonstrated the a~eurysm and also revealed pronounced elevation of the middle cerebral artery inthe lateral projection. A cyst in the left temporal region was aspirated in his home locality, and the patient wa,s referred to us. Repeat angiography at the Clinic confirmed the afore-mentioned findings (Fig. 9). Typical temporal-lobe automation seizures gradually developed, and the patient displayed a hypermaniacal personality. Under induced hypothermia at 30.50 C. (87 0 F.) for two hours,· a large· temporal-lobe cyst with lemon-Yellow fluid was evacuated, which uncovere<;l a huge aneurysm containing an organized clot (Fig. 10). All branches of the middle cerebral artery were first isolated and bathed in a 2.5.so1utionof papaverine.
1094
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
Fig. 10 (Case IV). Large aneurysm of left middle cerebral artery at sylvian fissure. The wall of the aneurysm lies beneath the cottonoid strip and the spatula; its origin was at the trifurcation of the middle cerebral artery.
Fig. 11 (Case IV). Specimen removed surgically. It consists of pieces of the aneurysm wall anda daughter aneurysm in the lower right hand corner. The daughter aneurysm was the only part that filled at angiography. Then a Schwartz clamp was placed across the left middle cerebral artery in the sylvian fissure proximal to the aneurysm, and aneurysmorrhaphy was done. At the base of the organized clot was a daughter aneurysm that had been demonstrated only by angiography. The clotted aneurysm and the daughter aneurysm were removed, and the aneurysmal wall was imbricated (Fig. 11). The Schwartz clamp was removed after an initial application of 9~ minutes followed by an additional application for three minutes. The early postoperative course showed only minimal paraphasia and right-sided weakness, which gradually cleared. A postoperative angiogram seven months later failed to demonstrate an aneurysm (Fig; 12). Petit mal seizures that had been present preoperatively still remain as this patient's ma.jor clinical problem.
Induced Hypothermia in Neurologic Conditions
1095
Fig. 12 (Case IV). Postoperative angiogram, indicating absence of aneurysm of left middle cerebral artery. The vessel again is in normal position; the aneurysm and the cyst have been removed.
Fig. 13 (Case V). Preoperative angiograms of aneurysm of right middle cerebral artery. CASE V. A 43-year-old healthy man was admitted to our service 24 hours after severe subarachnoid hemorrhage. Examination revealed a semicomatose state, left hemiparesis, stiff neck, bilateral papilledema, complete left homonymous hemianopsia, and extensive retinal and subconjunctival hemorrhage. Angiography five days later revealed a large aneurysm of the right middle cerebral artery near its trifurcation, with an intracerebral clot (Fig. 13). Operation under induced hypothermia was undertaken eight days after the hemorrhage. The middle cerebral artery proximal to the aneurysm was isolated with the patient at 280 C. (82 0 F.), and papaverine was applied. A Schwartz clip was applied, and a temporal-lobe hematoma was evacuated. The base of the aneurysm was exposed, tied with a black-silk ligature and wrapped with muscle. The Schwartz clamp was removed after 1572 minutes, with the blood pressure being maintained at 110/60. Warming was not forced, and the patient was responding
1096
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
Fig. 14 (Case V). Postoperative angiogram, demonstrating dilatation of right middle cerebral artery (arrow) near trifurcation, which is diBBimilar in appearance to the preoperative study.
well at 330 C. (91 0 F.) 2Y2 hours after refrigeration was discontinued. Convalescence was uneventful. At examination six months later, at which time the patient was operating his own farm, the papilledema had cleared and the visual fields were almost full. However, angiography showed dilatation in the middle cerebral artery near, the trifurcation dissjmilar to the appearance at the previous study; it was thought that this might represent a daughter aneurysm or a refill of the .original lesion due to loo~iming of the ligature (Fig. 14). The patient has remaines} well. COMPLICATIONS
:There were no serious complications that could be attributed directly to induced hypothermia, even though, as already emphasized, such radical procedures could not have been' undertaken under normothermic conditions'. Postoperative subdural hematomas did not develop. Wound healing was not prolonged, and the postoperative period in the hospital was not extended because of complications attributable to induced hypothermia. SUMMARY
Twenty patients with severe head injuries were subjected to induced hypothermia; 14 survived and six died. With this small series, no conclusions can be reached but further studies are warranted. Induced hypothermia as a therapeutic measure was used in nine patients with serious postoperative complications, with gratifying results being obtained in seven of these patients. Induced hypothermia was used in eight patients with brain tumo~s; satisfactory results were obtained in six of these patients. In each instance, it was thought that hypothermia offered the patient abetter
Induced Hypothermia in Neurologic Conditions
1097
opportunity to withstand a lengthy neurosurgical procedure when temporary interruption of a major blood vessel might be required for excision of the lesion. Nine aneurysms of the middle cerebral artery were attacked under hypothermia, with no deaths. In seven instances, a major artery was temporarily clipped for six to 24 minutes without serious neurologic deficit. Five patients with aneurysms of the internal carotid artery near the posterior communicating artery were operated on, with one death. The advantage of induced hypothermia in these aneurysms is debatable. One aneurysm of the left internal carotid artery near the bifurcation was attacked intracranially. During exposure, the left common carotid artery was permanently occluded and the right common carotid artery was occluded for nine minutes, with good results. Two aneurysms of the anterior cerebral artery were clipped, with excellent results in each instance. Seven patients with aneurysms of the anterior communicating artery were treated under hypothermia. Three patients had excellent results. Three postoperative deaths occurred; two patients died in the hospital and one died of rerupture one month after operation. The poor-risk patients tolerated hypothermia well but it failed to improve the results in this group of patients. CONCL USIONS
At this time, a specific opinion cannot be given relative to the advisability of recommending induced hypothermia in all neurosurgical procedures. The time of the over-all procedure is lengthened because the anesthetic time is prolonged. The time of the operation itself is not lengthened. However, the relaxed brain, the relative avascularity and the early postoperative recovery associated with hypothermia should receive favorable consideration in prolonged and difficult neurosurgical procedures in which temporary occlusion of a major blood vessel may have to be carried out. Induced hypothermia appears to afford the surgeon more time to plan his surgical procedure and allows him to carry it out more expeditiously. The patient appears to have a greater reserve in the event of sudden hemorrhage. It is our opinion that these seriously ill patients were benefited by the use of induced hypothermia, because a more deliberate and radical attack could be carried out with fewer complications than had we attempted to carry out similar procedures under normothermic conditions with the usual anesthetic techniques.
1098
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
REFERENCES 1. Adams, J. E. and Wylie, E. J.: Value of Hypothermic and Arterial Occlusion in the Treatment of Intracranial Aneurysms. Surg., Gynec. & Obst. 108: 631~635 (May) 1959. 2. Albert, S. N., Spencer, W. A., Boling, J. S. and Thistlethwaite, J. R.: Hypothermia in the Management of the Poor-Risk Patient Undergoing Major Surgery. J.A.M.A. 163: 1435~1438 (April 20) 1957. 3. Alexander, Eben, Jr., Davis, C. H., Jr. and Kester, Nancy C.: Intracranial Aneurysms: Methods of Treatment: Value of Hypothermia in the Surgical Approach. A.M.A. Arch. Neurol. & Psychiat. 81: 684~692 (June) 1959. 4. Bigelow, W. G., Lindsay, W. K., Harrison, R. C., Gordon, R. A. and Greenwood, W. F.: Oxygen Transport and Utilization in Dogs at Low Body Temperatures. Am. J. Physiol. 160: 125~137 (Jan.) 1950. 5. Boerema, 1., Wildschut, A., Schmidt, W. J. H. and Broekhuysen, L.: Experimental Researches into Hypothermia as an Aid in Surgery of the Heart: Preliminary Communication. Arch. chiI'. neerl. 3: 25--34, 1951. 6. Bohm, E., Gordon, D., Tovi, D. and Persson, P. 0.: A New Device for Induced Hypothermia in Intracranial Surgery. Acta chiI'. scandinav. 113: 1-8, 1957. 7. Botterell, E. H., Lougheed, W. M., Morley, T. P. and Vandewater, S. L.: Hypothermia in the Surgical Treatment of Ruptured Intracranial Aneurysms. J. Neurosurg. 15: 4~18 (Jan.) 1958. 8. Botterell, E. H., Lougheed, W. M., Scott, J. W. and Vandewater, S. L.: Hypothermia, and Interruption of Carotid, or Carotid and Vertebral Circulation, in Surgical Management of Intracranial Aneurysms. J. Neurosurg. 13: 1~42 (Jan.) 1956. 9. Burrows, M. M., Dundee, J. W., Francis, 1. L., Lipton, S. and Sedzimer, C. B.: Hypothermia for Neurological Operations. Anaesthesia 11: 4~ 18 (Jan.) 1956. 10. Crossman, L. W.: The Status of Refrigeration for Amputations and for Tissue Preservation. Am. J. Surg. n. s . .91: 92~98 (Jan.) 1956. 11. Crossman, L. W. and Alien, F. M.: Principles of Surgical and Therapeutic Refrigeration. S. Clin. North America, April, 1945, pp. 361~370. 12. Drew, C. E., Keen, G. and Benazon, D. B.: Profound Hypothermia. Lancet 1: 745~747 (April 11) 1!J5!J. 13. Dripps, R. D.: Physiologic Problems in Anesthesia Related to Induced Hypothermia. S. Clin. North America, Dec., 1955, pp. 1573~1578. 14. Eckenhoff, J. K: The Physiology of Hypothermia. Bull. New York Acad. Med. 34: 297~302 (May) 1958. 15. Fairley, H. B., Wad dell, W. G. and Bigelow, W. G.: Hypothermia for Cardiovascular Surgery: Acidosis in the Rewarming Period. Brit. J. Anaesth. 2,9: 310~318 (July) 1957. 16. Fay, T.: Clinieal Report and Evaluation of Low Temperature in Treatment of Cancer. Proc. Interstate Post-Grad. M. A. North America 1941, pp. 292~297. 17. Fay, Temple and Smith, G. W.: Observations on Reflex Responses During Prolonged Periods of Human Refrigeration. Arch. Neurol. & Psychiat. 45: 215~ 222 (Feb.) 1941. 18. Field, John, Il, Fuhrman, F. A. and Martin, A. W.: Effect of Temperature on the Oxygen Consumption of Brain Tissue. J. N europhysiol. 7: 117~ 126 (March) 1944. 19. Fleming, P. R. and Muir, F. H.: Electrocardiographic Changes in Induced Hypothermia in Man. Brit. Heart J. 19: 5!)~66 (Jan.) 1957. 20. Gillingham, F. J.: The Management of Ruptured Intracranial Aneurysm. Ann. Roy. CoIl. Surgeons England 23: 89~117 (Aug.) 1958. 21. Goffrini, Piero and Bezzi, Eugenio: L'lpotermia generale controllata in chirurgia. Pisa, Omnia Medica, 1954, pp. !J!J~106. 22. Laborit, H.: Neuroplegia et hibernation artificielle. J. Internat. CoIl. Surgeons 24: 704~728 (Dec.) 1!J55.
Induced Hypothermia in Neurologic Conditions
1099
23. Lazorthes, G. and Campan, L.: Hypothermia in the Treatment of Craniocerebral Traumatism. J. Neurosurg. 15: 162-167 (March) 1958. 24. Lewis, F. J.: Hypothermia in Cardiac and General Surgery. Minnesota Med. 38: 77-81 (Feb.) 1955. 25. Logue, Valentine: Surgery in Spontaneous Subarachnoid Haemorrhage: Operative Treatment of Aneurysms on the Anterior Cerebral and Anterior Communieating Artery. Brit. M. J. 1: 473-479 (March 3) 1956. 26. Lundberg, Nils, Nielsen, K. C. and Nilsson, Eric: Deep Hypothermia in Intracranial Surgery. J. Neurosurg. 13: 235-247 (May) 1956. 27. McMurrey, J. D., Bernhard, W. F., Taren, J. A. and Bering, E. A., Jr.: Studies on Hypothermia in Monkeys. 1. The Effect of Hypothermia on the Prolongation of Permissible Time of Total Occlusion of the Afferent Circulation of the Brain. Surg., Gynec. & Obst. 102: 75-86 (Jan.) 1956. 28. Martin, J. T., Faulconer, Albert, Jr. and Bickford, R. G.: Electroencephalography in Anesthesiology. Anesthesiology 20: 359-376 (May-June) 1959. 29. Meyer, J. S. and Hunter, John: Effects of Hypothermia on Local Blood Flow and Metabolism During Cerebral Ischemia and Hypoxia. J. Neurosurg. 14: 210227 (March) 1957. 30. Petit-Dut&illis: Hibernation in Neurosurgery. Rev. path. gen. et comp. 669: 939,1955. 31. Pontius, R. G., Bloodwell, R. D., Cooley, D. A. and DeBakey, M. E.: The Use of Hypothermia in the Prevention of Brain Damage Following Temporary Arrest of the Cerebral Circulation: Experimental Observations. Am. Coli. Surgeons, Clin. Congo (40th), Proc. S. Forum 5: 224-228, 1954. 32. Pontius, R. G. and DeBakey, M. E.: Experimental and Clinical Observations on the Use of Hypothermia to Prevent Ischemic Damage to the Central Nervous System. The Physiology of Induced Hypothermia. NAS-NRC. Publication 451: 264-270, 1955. 33. Pool, J. L., Jacobson, Sherwood and Fletcher, T. A.: Cerebral VasospasmClinical and Experimental Evidence. J.A.M.A. 167: 1599-1601 (July 26) 1958. 34. Pool, J. L., Ransohoff, Joseph, Yahr, M. D. and Hammill, J. F.: Early Surgical Treatment of Aneurysms of the Circle of Willis. Neurology 9: 478-486 (July) 1959. 35. Pratt, G. H. and Collins, V. J.: Controlled Hypothermia as an Ancillary Surgical Procedure. S. Clin. North America, April, 1956, pp. 405-422. 3G. Ripstein, C. B., Friedgood, C. E. and Solomon, N.: Technique for Production of Hypothermia: Preliminary Report. Surgery 35: 98-103 (Jan.) 1954. 37. Rose, J. C., McDermott, T. F., Lilienfield, L. S., Porfido, F. A. and Kelley, R. T.: Cardiovascular Function in Hypothermic Anesthetized Man. Circulation 15: 512-517 (April) 1957. 38. Rosomoff, H. L.: Hypothermia and Cerebral Vascular Lesions. H. Experimental Middle Cerebral Artery Interruption Followed by the Induction of Hypothermia. Research Report: Project NM 007 081. 30.04 Naval Medical Research Institute. 39. Rosomoff, H. L. and Gilbert, Robert: Brain Volume and Cerebrospinal Fluid Pressure During Hypothermia. Am. J. Physiol. 183: ]9-22 (Oct.) 1955. 40. Rosomoff, H. L. and Holaday, D. A.: Cerebral Blood Flow and Cerebral Oxygen Consumption During Hypothermia. Am. J. Physiol. 179: 85-88 (Oct.) 1954. 41. Sedzimir, C. B. and Dundee, J. W.: Hypothermia in the Treatment of Cerebral Tumors. J. Neurosurg. 15: 199-206 (March) 1958. 42. Stone, H. H., MacKrell, T. N., Truter, Mary R., Donnelly, Celeste and Frobese, A. S.: The Effects of Lowered Body Temperature on the Cerebral Hemodynamics and Met&bolism of Man. Am. Coli. Surgeons, Clin. Congo (41st), Proc. S. Forum 6: 129-134, 1955. 43. Uihlein, Alfred and Lippert, R. G.: Unpublished data. 44. Vandewater, S. L., Lougheed, W. M., Scott, J. W. and Botterell, E. H.: Some
1100
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
Observations with the Use of Hypothermia in Neurosurgery. Anesth. & Analg. 37: 29-36 (Jan.-Feb.) 1958. 45. Virtue, R. W.: Hypothermic Anesthesia. Spring field, Illinois, Charles C Thomas, Publisher, 1955, 62 pp. 46. White, R. J., Uihlein, Alfred, and Grindlay, J. H.: The Design and Application of a Hydraulic Arterial Clamp for External Control of Cerebral Blood Flow. Am. ColI. Surgeons, Clin. Con/!:. (44th), Proc. S. Forum 9: 733-735, 1958.
THE use of induced hypothermia as an adjunct to neurosurgical techniques and to the treatment of certain neurologic conditions prompts both speculation and hope. Many physiologic problems remain to be solved; however, one easily may anticipate the time when neurosurgical procedures can be accomplished with the help of the relatively bloodless fIeld now familiar to the cardiac surgeon. Our purpose is to review briefly the physiologic data now assembled concerning induced hypothermia2 , 7,21-23, 30, 41, 44, 45 and to present our experience with a series of neurosurgical patients on whom this technique was used. The use of cooling as an analgesic agent probably predates medicine as a science, for the injured part was frequently placed in cold water to relieve pain or inflammation. In the 1930's, Fay and Fay and Smith maintained the human body for days at temperatures between 25° and 30° C. to allay the pain associated with inoperable carcinoma. Later, Crossman and AlIen were instrumental in introducing refrigeration as an anesthetic agent in amputations for gangrene. Pratt and Collins found this method satisfactory, and others10 have reported similar successes. Pontius and DeBakey have shown experimentally that the brain withstands hypothermia well. A number of investigators 4, 6, 9, 26, 39, 40 have shown that the body's metabolic requirements can be decreased by hypothermia 2, 4, 29 and that the oxygen demand is decreased by lowered temperatures ;12, 18 therefore, it was considered that essential circulation to certain parts of the body could be interrupted safely for longer periods of time with refrigeration than without. 8 , 27, 31, 32, 38 Further experimental work by cardiac surgical research teams demonstrated that induced hypothermia consistently reduces the oxygen consumption of tissues proportionate to the degree of lowered temperature,13 if shivering is prevented, and that, as the temperature is dropped, the blood pressure becomes lowered, the pulse rate reduced and the respiratory rate slowed. 87
1079
1080
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
PHYSIOLOGY
Central Nervous System
Under normothermic conditions, cerebral ischemia produces a rapid and profound insult to the brain. Many reports attest to the speed with which flattening occurs in electroencephalographic tracings following cerebral circulatory arrest. 28 Vandewater and associates achieved occlusion times of 15 minutes and 10 seconds with both carotid and both vertebral arteries at 26.60 C. (79.8 0 F.) in one patient, and occlusion of both carotid arteries for 15 minutes at 26.50 C. (79.7 0 F.) in another patient without neurologic sequelae resulting from the occlusion in either instance. This represents a significant protection afforded by hypothermia that aids in the surgical treatment of vascular malformations or highly vascular tumors. Rosomoff and Holaday found an increase in cerebral vascular resistance and a reduction in cerebral blood flow in dogs under hypothermia. This reduction in cerebral blood flow was associated with an unchanged arteriovenous oxygen difference; therefore, the cerebral metabolic rate must decrease with a fall in temperature. Eckenhoff stated that this is a linear relationship down to an oxygen consumption of 50 per cent at 250 C. In hypothermic dogs, Rosomoff and Gilbert have noted a 4 per cent decrease in the bulk of the brain and a 31 per cent increase in the extracerebral intracranial space, the so-called slack brain, as well as a decrease in venous pressure and the pressure of cerebrospinal fluid. These pressures were greatly increased with shivering, however. Using three human volunteers, Stone's group confirmed these data and showed that shivering could increase oxygen demands from 76 per cent at 83 0 F. to more than 100 per cent without any change in temperature. Cardiovascular Effects
Hypothermia produces bradycardia of a degree almost directly related to the amount of decrease in temperature,14 This linear relationship does not apply to blood pressure. The electrocardiogram in hypothermia is affected by such factors as the blood oxygen and carbon dioxide pressures, the pH, and the electrolyte concentration. I9 In general, the usual changes associated with cooling to temperatures above 28 0 or 29 0 C. appear to be low-voltage or absent P waves, prolongation of the QRS and ST intervals, and inversion of the T waves. Fleming and Muir reported 29 cases in which hypothermia was used for cardiovascular surgery and confirmed the presence of a prolonged PR interval in many instances. Varying degrees of heart block and alterations of rhythm are more common with temperatures below 28 0 to 30 0 C., but warming the patient reverses these changes,15. 24
Induced Hypothermia in Neurologic Conditions
1081
Rose and co-workers cooled patients who did not have cardiovascular disease and measured cardiac output, stroke volume, mean arterial pressure, peripheral resistance, cardiac work, mean circulation time, central blood volume, and the percentage of packed cells (hematocrit). None of the changes were consistent or of statistical significance. The major hazard of hypothermia is vent:-icular fibrillation. However, in the absence of cooling below 28° or 29° C., or direct cardiac manipulation, electrolyte imbalance and hypoxia, the occurrence of ventricular fibrillation should be uncommon. Ventricular extrasystoles may be considered as precursors to fibrillation; when they are present, ventilation should be increased and partial or complete warming considered. Since neurosurgery does not require cardiac manipulation, some of the adverse effects of hypothermia on cardiac rhythm associated with cardiac surgery do not apply. Should fibrillation occur, prompt thoracotomy and cardiac massage are indicated to restore rhythm and perfusioll unless cooling is being done internally by a pump-oxygenator. Adequate treatment of ventricular fibrillation under hypothermic conditions may be difficult. METHODS OF ACHIEVING HYPOTHERMIA
Induced hypothermia requires that the homeothermal controls and heat-production mechanisms of constant-temperatured man be overcome. ll Thereafter, any decrease in environmental temperature will be reflected in loss of heat from the body. Many drugs have been used to facilitate cooling. Currently, general anesthesia has almost completely replaced the "lytic cocktail" as a means of obtunding the homeothermal regulators of the central nervous system. 22 • 30 Shivering can be controlled with relaxants, by the use of deeper levels of anesthesia, or by the intravenous injection of chlorpromazine or promethazine (Phenergan). The application of cold then effects a lowering of body temperature to the desired levels. Methods of cooling vary widely.7. 36 For simplicity, one might modify the classification of Eckenhoff as follows: A.
EXTERNAL SURFACE COOLING
1. Immersion in water. An anesthetized patient is placed in a whole-body
water bath and ice is added. This inexpensive method produces a rapid decrease in temperature. 2. Cooling blankets (Davol, Therm-O-Rite, etc.). An anesthetized patient is placed between blankets containing imbedded coils through which a coolant solution flows either by gravity or from a heater-cooler pump unit. This gives slow cooling and warming with more control than does the ice bath but it is more costly in time and equipment. 3. Forced-air units (Autohypotherm refrigeration bed).6 These units force large volumes of cooled or warmed air around the patient in a tight en-
1082
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
closure. They are relatively new, are not widely employed in the United States, and are rather expensive. 4. Direct application of ice bags, coolant bags or cracked ice. This method may be used alone or to supplement use of the mattresses. 5. Suspension of the body in a deep-free.ze unit. B.
INTERNAL SURFACE COOLING
1. Circulation through a stomach balloon. 2. I cc-water enema. 3. Cold saline solutions poured into the thorax or abdomen, or packed about the aorta. C. INTERNAL VASCULAR COOLING (PUMP-OXYGENATOR)
This requires removal of blood, cooling it by heat exchangers, and restoring it to the circulation, with or without the use of an extra pump or an oxygenator. This can be an extremely rapid form of cooling, especially if it is associated with extracorporeal circulation. CLINICAL DATA
Since 1955, induced hypothermia has been used in various aspects of an active neurosurgical service at the Mayo Clinic (Table 1). It has been employed therapeutically as early as possible after admission to the hospital in 20 cases of acute head injuries to combat coma, extensor spasm, decerebrate rigidity, opisthotonus and hyperpyrexia. Fourteen of these patients survived and six died. The results have been gratifying in some instances and disappointing in others; the over-all picture suggests that this form of treatment may be lifesaving and should be considered. We have been well satisfied with the use of blankets for cooling these patients, because it reduces nursing care and permits a more accurate control of hypothermia. In one patient, hypothermia was maintained for as long as a week, the rectal temperature being maintained at about 33 0 C. (91 0 F.), with complete recovery from a severe neurologic defic:t. Table 1.
Hypothermia in Neurosurgery: 51 Cases
CONDITION
Berry aneurysms ... " ......... . Brain tumors. . . . . . . . . . . . . . . . . .. . .. . Meningiomas. . . . . . . . . . . . . . ....... . Gliomas .............. . Craniopharyngioma ............... . Hemangioma ........ . Head injuries ........... . Postoperative ............... . TOTAL . . . . . . . . . . . . . . . . . . . . . . . . .
CASES
3 3
1 1
24 8
20 9
61
Induced Hypothermia in Neurologic Conditions
1083
We have used induced hypothermia in the treatment of nine patients with postoperative complications manifested by progressive stupor, hyperpyrexia and cerebral edema in patients operated on for parasellar lesions encroaching on the hypothalamus, for subdural hematomas and for brain abscesses. The dramatic recovery in seven of nine such patients who had failed to improve with the usual therapeutic efforts was impressive enough to justify its further application. In these patients, the rectal temperature was not decreased to less than 33 0 C. (91 0 F.), as a rule. Varying degrees of shivering were noted, and it was difficult to control shivering below this temperature. We have employed induced hypothermia in the surgical attack on intracranial vascular tumors, aneurysms of the circle of Willis, arteriovenous malformations, and certain brain tumors. Experience with the use of induced hypothermia in the treatment of any of these conditions is necessarily limited, except possibly in the case of bleeding intracranial aneurysms, so that long-term follow-up studies must be conducted before we know whether induced hypothermia has improved the surgical attack as well as the clinical results. BRAIN TUMORS
Eight patients with brain tumors were selected for treatment with induced hypothermia. The lesions included three recurrent hemispheric gliomas, three meningiomas, an intracerebral hemangioma and a craniopharyngioma. Two postoperative failures were noted. One patient with a recurrent glioma died of hemispheric infarction and cerebral edema. In the other patient, a large meningioma of the sphenoid ridge was resected, with severe loss of blood; in addition, there was severe cerebral edema with hypertension, for which large amounts of trimethaphan camphorsulfonate (Arfonad) were administered. It was thought that a combination of factors was responsible for this patient's death, namely hypothermia of 29° C. for 11 hours, excessive loss of blood, although the loss was adequately replaced, and large doses of a hypotensive drug. Extensive renal damage was found at necropsy. The other six patients responded well to hypothermia and recovered uneventfully. The "slack brain" reported with vascular lesions is not so apparent with brain tumors in our experience; capillary oozing appears to be lessened and the postoperative recovery period is shorter than with conventional types of anesthesia. INTRACRANIAL ANEURYSMS
A total of 24 verified intracranial aneurysms have been operated on at the Clinic in patients under induced hypothermia, the temperatures
1084
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
Fig. 1. Equipment used for induced hypothermia. The Therm-O-Rite blanket is on the table, with the refrigeration unit and oscilloscope on the right, and the inhalation anesthesia unit on the left.
ranging between 27° C. and 31 ° C. The Therm-O-Rite blanket waEl used in each instance to cool and then warm the patient (Fig. 1); General anesthesia always was used and respirations were controlled. A malleable spinal-puncture needle was inserted into the lumbar subarachnoid space in some patients to remove cerebrospinal fluid when required. This procedure cannot be used when the patient is immersed in ice water to induce hypothermia. Surgical exposure of the carotid and vertebral arteries is carried out when indicatedl while the temperature is being lowered, followed by craniotomy. The aneurysm is exposed when the desired level of hypothermia is attained. To prevent serious hemorrhage at the time of exposure of the aneurysm, the carotid and vertebral arteries can be occluded by tapes or a hydraulic clamp48 for varying periods, or the afferent intracranial artery can be occluded temporarily by means of an Olivecrona, a Mayfield or a Schwartz clip after the vessel wall is covered with a pad of cotton soaked in a 2.5 per cent solution of papaverine.20 • aa After aneurysmal repair, the temporary occlusive device is removed. In our opinion, the postoperative neurologic deficit is less than that resulting from similar procedures carried out under normothermic conditions. Warming of the patient is begun I1S soon as the definitive operation is accomplished by increasing the temperature of the circulating solution in the blanket to 43° C. (110° F.). Gradual warming prevents burning of the skin and permits the surgeon to check hemostasis before closure
Induced Hypothermia in Neurologic Conditions
1085
of the wound. The patient frequently responds to verbal commands when his body temperature reaches 330 C. (91 0 F.) and his vital signs are stabilized. One patient whose temperature was 300 C. (86 0 F.) asked for hot soup when he arrived on the ward. Should compensatory hyperpyrexia develop in the early postoperative period, it can be controlled by the use of one half of the refrigeration blanket. Selection of Patients
Our policy has been to perform bilateral carotid angiography as soon as the patient's condition warrants the procedure and to operate on the verified aneurysm when the time appears most propitious. The site and size of the aneurysm, the presence of an intracranial clot, the presence of arterial spasm, the age of the patient and the severity of the neurologic deficit are all factors that haye been considered in the selection of our patients for induced hypothermia. The policy for selection is arbitrary and is left to the discretion of the surgeon in charge of each patient. To analyze our selection, the patients were grouped into four grades with regard to operative risk. Grade 1 indicates a patient who is conscious, with or without a significant neurologic deficit and with or without blood in the subarachnoid space. Grade 2 represents a drowsy patient with some neurologic deficit but who is stabilized. Grade 3 represents a drowsy patient with a definite neurologic deficit, retinal hemorrhage and early papilledema. Grade 4 indicates a deteriorating patient who is nearly moribund, with a major neurologic deficit, grossly bloody cerebrospinal fluid, hypertension and severe nuchal rigidity. The results of the surgical treatment with induced hypothermia were classified into four categories. "Excellent" means the patient is well, with no neurologic deficit; "good" means a patient who is well and working but who has a minimal neurologic deficit; "fair" indicates some aphasia and hemiparesis; "poor" indicates a major neurologic deficit, with no improvement over the preoperative condition or a state that is even worse. All the patients were selected for induced hypothermia because, in the opinion of the surgeon, this method appeared to offer more protection to the patient under the given circumstances. Hypothermia was selected in several instances because the presence of degenerative vascular changes was suspected as the result of angiography. During the same period, 82 patients with intracranial aneurysms were treated surgically without hypothermia; of this group, 47 had craniotomy and an additional 18 had craniotomy with carotid ligation. Aneurysms in various locations were operated on with the aid of induced hypothermia. We have analyzed the techniques used and the surgical results in each instance, according to the location of the aneurysm. The estimated preoperative risk of the patients, their age and the number
1086
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
of days from the last subarachnoid hemorrhage, along with the postoperative results, also were studied and will be presented in another publication. 43 The number of patients admittedly is small, but the results obtained under the circumstances appear to justify further use of this technique in selected instances. We do not wish to advocate that every patient with a bleeding aneurysm should be subjected to induced hypothermia. However, if it may be necessary to interrupt temporarily the arterial supply to the brain or a segment thereof, this can be accomplished with less danger of a serious neurologic deficit under induced hypothermia than under normothermic conditions. As others have reported,3. 20. 26, 33, 34 the best surgical results are anticipated in patients whose operative risk is graded 1 or 2. However, five of our patients in the grade 3 category of operative risk made gratifying recoveries. No patient whose operative risk was graded 4 recovered, even with hypothermia; however, all such patients were operated on in desperation. In two of these patients, the internal carotid artery tore as a clip was applied, necessitating permanent ligation, with subsequent cerebral infarction. Another patient whose risk was graded 4 was subjected to a second attack on an aneurysm of the anterior communicating artery under hypothermia and died of meningitis on the tenth postoperative day. This was a surgical triumph but the patient died. Definitive treatment of aneurysms under hypothermia demonstrates that major vessels can be occluded for relatively long periods without. appreciably altering the postoperative results. The singular advant.age of temporary occlusion of the afferent artery proximal to the aneurysm (designated as "clip min." in the tables) apparently merits its use in the treatment of aneurysms of the middle cerebral artery and those of the anterior cerebral-anterior communicating arteries. This technique appears to be more practical than does temporary occlusion of both carotid arteries in the neck, along with the vertebral arteries. l A vasodilator, such as a 2.5 per cent solution of papaverine, should be applied to the wall of the artery before the temporary clip is applied. 20 • 25, 33 Under normothermic conditions, this technique probably would not be so successful. Results
INTERNAL CAIW'l'ID ARTEHY. Aneurysms of the internal carotid artery were divided into those in the region of the posterior communicating artery and those in the region of the carotid bifurcation (Table 2). Five patients with the former type of lesion and one with the latter type were operated on under hypothermia. All patients represented grade 1 or 2 operative risks except one, in whom the risk was graded as 4. The one patient whose aneurysm was near the bifurcation was operated Oll
Induced Hypothermia in Neurologic Conditions Table 2. AGE (yr.) PREOP. AND SIDE HISK
1087
Hypothermia in Cerebral Aneurysms
DAYS FROM BLEEDING TO OPERATION
CLIP OH MUSC.
CLIP
(min.)
PAPAV- TEMP. ERINE (QC.)
RESULT
(2.5%)
Internal carotid near posterior communicating 47 L+R 52 R 59 R 55 R 64 L
43
1+ (mult.) 2 2 2 4
21 53 10*
C (R)
0
No
C
1.5
Yes
M C C
0 0 0
No No No
30 Excellent; 3rd nerve improved 29 Good; resid. hemiparesis 29 Good 29 Excellent 29 Died
Anterior cerebral 46R 61 R
3
10* 15 C (subdural) 24 11 C+M 0
Yes
29
Excellent
No
30 Excellent; facetious
Internal carotid near bifurcation 25 L
2
9*
M
t
No
29
Good; dysphasia
* Hematoma present.
t 9 minutes RCC; permanent on LCC.
nine days after her last hemorrhage, with good results. None of the patients with posterior communicating aneurysms were operated on less than ten days after the last hemorrhage. Of these, the one with the grade 4 risk died shortly after operation, while the remainder were improved. ANTERIOH CEREBRAL ARTERY. Two patients who had aneurysms of the anterior cerebral artery proximal to the anterior communicating artery were operated on, with excellent results (Table 2). In both instances, the aneurysms were clipped. One patient had a contralateral subdural hematoma in the parietal region that was evacuated first; two weeks later, the aneurysm of the right anterior cerebral artery was attacked after the anterior cerebral artery on either side of the aneurysm was occluded by means of Schwartz' clips for 15 minutes before clipping the neck of the aneurysm. MIDDLE CEREBRAL AH'l'ERY. Nine patients with aneurysms of the middle cerebral artery near the trifurcation were operated on under hypothermia without a death (Table 3). Five patients had massive intracerebral clots. One patient was unimproved. Aneurysmorrhaphy was
1088
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
Frontal
\
\
Ane1.:1~"\jsm.
opened
.
Fig. 2. Aneurysm of right middle cerebral artery: View at operation, showing the temporary clip on the middle cerebral artery, aneurysmorrhaphy, and ligation of the neck of the aneurysm. Table 3.
Hypothermia in Cerebral Aneurysms: Middle Cerebral Artery N ear Trifurcation
AGE (yr.) PREOP. AND SIDE RISK
DAYS FROM CLIP BLEEDING TO OR OPERATION MUSC.
CLIP
(min.)
PAPAV- TE:\(P. ERINE (OC.)
(2.5%)
36R 43R
3
1
90 8*
M
t
7 15.5
No Yes
48L 31 L
3 3
22 14*
C C
0 9
No Yes
40L
2
23
M
0
No
22L
2
6*
C
8.5
Yes
27L 50R 43 L
2 1 1
8 yr.* 17 29*
t
9.5 12 24
Yes No No
C C+M
RESULT
Excellent; focal seiz. Good; minimal field defect 29.5 Good; apraxia 30 Good; resid. mild aphasia 31 Unimp.; hemipl., aphasia. field def. 29 Good; minimal aphasia 30 Ex('Pl1ent 29 Excellent 28.5 Excl'llent; min. dysphasia 28 28
• Hematoma present. t Aneurysmorrhaphy.
carried out with excellent or good results in two patients who had large aneurysms after temporary clipping of the middle cerebral artery proximal to the aneurysm (Figs. 2 and 3). These results represent a surgical triumph because of the size of the aneurysm and the radical approach,
Induced Hypothermia in Neurologic Conditions
1089
Fig. 3. Large aneurysm (arrows) of left middle cerebral artery near trifurcation, demonstrating elevation and mesial displacement of middle cerebral artery by intracerebral mass lesion. Table 4.
Hypothermia in Cerebral Aneurysms: Anterior Cerebral-Anterior Communicating Arteries
AGE (yr.) PREOP. AND SIDE RISK
DAYS FROM CLIP BLEEDING TO OR OPERATION MUSC.
46R
4
9
63 L
3 2
44L 62 R 52R 51 L 42R
3-4
1 1 4
CLIP
(min.)
PAPAVTEMP. ERlNE
(2.5%)
C
5
Yes
28
C+M
1
Yes
8 13* 10 17 7*
C M M C C
5 0 0 0 5
Yes No No No Yes
(OC.)
RESULT
28 Died 13 days p. 0 . , meningitis 31 Died at home, 1 mo.; recur. hem. 28 Excellent 30 Unimproved 30 Excellent 31 Excellent 29 Died
* Hematoma present.
with minimal sequelae. Without hypothermia, this operation would not have appeared practical. Varying periods of occlusion were used; the longest period was 24 minutes and was followed by excellent results. ANTERIOR CEREBRAL-ANTERIOR COMMUNICATING ARTERIES. Seven patients with aneurysms at the juncture of the anterior communicating and anterior cerebral arteries were operated on (Table 4). Only one had an intracerebral clot; this patient represented a grade 4 operative risk and died after operation. The two other surgical deaths in this group were mentioned earlier. The remainder of these patients survived their direct surgical attack. One of these died at home one month later of recurrent hemorrhage when the Olivecrona clip came off. The other three patients had an excellent postoperative recovery.
1090
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN November 25
27
26 In blalnket
106 104 ~ 102
::.
.... 100 ~
~
~
~
98
.--
~
~
96 94 92
90 Intake·cc Output·cc
Cl
CO 2
1800-2000 850-960 93 18
NOv.23-lntra and extrasellor chromophobe adenoma removed
Fig. 4 (Case I). Control of hyperpyrexia by induced hypothermia after removal of pituitary turnor.
Illustrative Cases
The following cases are representative of the type of patient that was selected for induced hypothermia and demonstrate the need for further studies of this technique. The first case is an example in which hypothermia was used therapeutically in the early postoperative period, while the others illustrate the type of patient selected for induced hypothermia rather than for some other form of surgical approach. The therapeutic use of refrigeration was graphically illustrated in the two following patients. CASE 1. On the third day after uneventful removal of a chromophobe adenoma of the pituitary, a 57-year-old man experienced the development of pronounced edema of the face and the conjunctival and orbital structures, with hyperpyrexia, loss of consciousness, dilatation of the pupils and bilateral Babinski's signs. Despite use of the usual measures for combating edema and maintaining the electrolyte balance, the patient's condition continued to worsen. After 48 hours of refrigeration by blanket, gradual improvement occurred in this patient's convalescence from a relatively hopeless situation to complete recovery, although the body temperature never decreased below 98° F. (Fig. 4). CASE H. A 46-year-old man had a bleeding aneurysm of the anterior communicating artery that initially was wrapped with muscle without hypothermia, as it appeared to be hazardous at the time to apply a clip. He recovered satisfactorily for six months, when he had a recurrence of severe hemorrhage. He was admitted to our service in coma, with bilaterally dilated and fixed pupils, CheyneStokes respiration and bilateral extensor spasm. His condition appeared hope-
Induced Hypothermia in Neurologic Conditions January
1091
5
4
106r-----------,------------, 104 '»
102
(
In blanket
)
...::, 100 ~
~
~
Ob
98
~ 96
e
~
94
92 90 Urea Cl CO2
No
30 93 26 135
Dec. 6-Anterior communicating artery aneurysm wrapped with muscle
Fig. 5 (Case II). Induced preoperative hypothermia after acute subarachnoid hemorrhage.
Fig. 6 (Case II). Postoperative right carotid angiogram, showing persistence of aneurysm of anterior communicating artery. less. Pure blood was present in the cerebrospinal fluid. The patient was placed in the refrigeration blanket for 48 hours (Fig. 5.) The coma lessened graduallv. the extensor rigidity disappeared, pupillary responses returned, and the patient recovered sufficiently to permit angiography (Fig. 6) and re-exploration one week after his last hemorrhage. Re-exploration under induced hypothermia at 28 0 C. (820 F.) permitted evacuation of an intracerebral clot in the right frontal region that extended into the right lateral ventricle and filled it. A clot cast of the ventricle was aspirated. The aneurysm then was successfully clipped, sparing both anterior cerebral arteries. The patient's postoperative convalescence was most remarkable until the tenth postoperative day, when staphylococcic meningitis developed and he died. To survive massive intracerebral and intraventricular hemorrhage to a sufficient degree to permit reoperation appeared to justify
1092
ALFRED UIHLEIN, ROWARD TERRY, JR., JOHN MARTIN
Fig. 7 (Case Ill). Preoperative angiograms of aneurysm of anterior cerebral artery (arrows), showing shift of anterior cerebral vessels to right of midline by left parietal subdural hematoma. The lateral projection shows the elongated aneurysm, with forward compression of the sylvian vessels on the left by the subdural hematoma. the assumption that we would not have had a ~econd opportunity to attack his bleeding aneurysm without the early use of therapeutic refrigeration.
Induced hypothermia offers the surgeon certain allies in attacking bleeding intracranial aneurysms, as illustrated by the following case reports. CASE Ill. A 46-year-old woman was admitted to the hospital five days after the last of a series of three spontaneous subarachnoid hemorrhages, confirmed by the presence of blood in the cerebrospinal fluid, stiff neck and nausea. Angiography two days after admission revealed an aneurysm of the right anterior cerebral artery that filled via both systems, with a shift of the distal anterior cerebral complex to the right in the anteroposterior projection and forward compression of the left sylvian vessels in the lateral projection (Fig. 7). Left parietal craniotomy three days later uncovered a large subdural clot over the parietotemporal region that was evacuated. Two weeks later, under induced hypothermia at 29 0 C. (84 0 F.) for two hours, the aneurysm and both anterior cerebral arteries were exposed. The left anterior cerebral artery was smaller than the right, and cottonoid strips soaked in papaverine were applied. The right anterior cerebral artery was temporarily clipped with a Schwartz bulldog clamp for 15 minutes, while the neck of the aneurysm was tied with a black-silk ligature and an Olivecrona clip was placed over the decompressed aneurysmal sac. The Schwartz clamp then was removed. Recovery was excellent, and she returned to her secretarial position. An angiogram four months later showed no evidence of an aneurysm (Fig. 8). CASE IV. A 27-year-old robust man was admitted to the hospital in February, 1958. His first subarachnoid hemorrhage had occurred in November, 1950, with recovery. A convulsive disorder had developed in 1955. An angiogram elsewhere
Induced Hypothermia in Neurologic Conditions
1093
Fig. 8 (Case In). Postoperative angiogram, showing clip (arrow) at site of previous aneurysm.
Fig. 9 (Case IV). Preoperative angiograms, showing aneurysm ofleft middle cerebral artery. (See text for details.)
in October, 1956, had revealed an aneurysm of the left middle cerebral artery midway between the bifurcation of the carotid artery and the trifurcation of the middle cerebral artery. Repeat angiography elsewhere in January, 1958., had demonstrated the a~eurysm and also revealed pronounced elevation of the middle cerebral artery inthe lateral projection. A cyst in the left temporal region was aspirated in his home locality, and the patient wa,s referred to us. Repeat angiography at the Clinic confirmed the afore-mentioned findings (Fig. 9). Typical temporal-lobe automation seizures gradually developed, and the patient displayed a hypermaniacal personality. Under induced hypothermia at 30.50 C. (87 0 F.) for two hours,· a large· temporal-lobe cyst with lemon-Yellow fluid was evacuated, which uncovere<;l a huge aneurysm containing an organized clot (Fig. 10). All branches of the middle cerebral artery were first isolated and bathed in a 2.5.so1utionof papaverine.
1094
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
Fig. 10 (Case IV). Large aneurysm of left middle cerebral artery at sylvian fissure. The wall of the aneurysm lies beneath the cottonoid strip and the spatula; its origin was at the trifurcation of the middle cerebral artery.
Fig. 11 (Case IV). Specimen removed surgically. It consists of pieces of the aneurysm wall anda daughter aneurysm in the lower right hand corner. The daughter aneurysm was the only part that filled at angiography. Then a Schwartz clamp was placed across the left middle cerebral artery in the sylvian fissure proximal to the aneurysm, and aneurysmorrhaphy was done. At the base of the organized clot was a daughter aneurysm that had been demonstrated only by angiography. The clotted aneurysm and the daughter aneurysm were removed, and the aneurysmal wall was imbricated (Fig. 11). The Schwartz clamp was removed after an initial application of 9~ minutes followed by an additional application for three minutes. The early postoperative course showed only minimal paraphasia and right-sided weakness, which gradually cleared. A postoperative angiogram seven months later failed to demonstrate an aneurysm (Fig; 12). Petit mal seizures that had been present preoperatively still remain as this patient's ma.jor clinical problem.
Induced Hypothermia in Neurologic Conditions
1095
Fig. 12 (Case IV). Postoperative angiogram, indicating absence of aneurysm of left middle cerebral artery. The vessel again is in normal position; the aneurysm and the cyst have been removed.
Fig. 13 (Case V). Preoperative angiograms of aneurysm of right middle cerebral artery. CASE V. A 43-year-old healthy man was admitted to our service 24 hours after severe subarachnoid hemorrhage. Examination revealed a semicomatose state, left hemiparesis, stiff neck, bilateral papilledema, complete left homonymous hemianopsia, and extensive retinal and subconjunctival hemorrhage. Angiography five days later revealed a large aneurysm of the right middle cerebral artery near its trifurcation, with an intracerebral clot (Fig. 13). Operation under induced hypothermia was undertaken eight days after the hemorrhage. The middle cerebral artery proximal to the aneurysm was isolated with the patient at 280 C. (82 0 F.), and papaverine was applied. A Schwartz clip was applied, and a temporal-lobe hematoma was evacuated. The base of the aneurysm was exposed, tied with a black-silk ligature and wrapped with muscle. The Schwartz clamp was removed after 1572 minutes, with the blood pressure being maintained at 110/60. Warming was not forced, and the patient was responding
1096
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
Fig. 14 (Case V). Postoperative angiogram, demonstrating dilatation of right middle cerebral artery (arrow) near trifurcation, which is diBBimilar in appearance to the preoperative study.
well at 330 C. (91 0 F.) 2Y2 hours after refrigeration was discontinued. Convalescence was uneventful. At examination six months later, at which time the patient was operating his own farm, the papilledema had cleared and the visual fields were almost full. However, angiography showed dilatation in the middle cerebral artery near, the trifurcation dissjmilar to the appearance at the previous study; it was thought that this might represent a daughter aneurysm or a refill of the .original lesion due to loo~iming of the ligature (Fig. 14). The patient has remaines} well. COMPLICATIONS
:There were no serious complications that could be attributed directly to induced hypothermia, even though, as already emphasized, such radical procedures could not have been' undertaken under normothermic conditions'. Postoperative subdural hematomas did not develop. Wound healing was not prolonged, and the postoperative period in the hospital was not extended because of complications attributable to induced hypothermia. SUMMARY
Twenty patients with severe head injuries were subjected to induced hypothermia; 14 survived and six died. With this small series, no conclusions can be reached but further studies are warranted. Induced hypothermia as a therapeutic measure was used in nine patients with serious postoperative complications, with gratifying results being obtained in seven of these patients. Induced hypothermia was used in eight patients with brain tumo~s; satisfactory results were obtained in six of these patients. In each instance, it was thought that hypothermia offered the patient abetter
Induced Hypothermia in Neurologic Conditions
1097
opportunity to withstand a lengthy neurosurgical procedure when temporary interruption of a major blood vessel might be required for excision of the lesion. Nine aneurysms of the middle cerebral artery were attacked under hypothermia, with no deaths. In seven instances, a major artery was temporarily clipped for six to 24 minutes without serious neurologic deficit. Five patients with aneurysms of the internal carotid artery near the posterior communicating artery were operated on, with one death. The advantage of induced hypothermia in these aneurysms is debatable. One aneurysm of the left internal carotid artery near the bifurcation was attacked intracranially. During exposure, the left common carotid artery was permanently occluded and the right common carotid artery was occluded for nine minutes, with good results. Two aneurysms of the anterior cerebral artery were clipped, with excellent results in each instance. Seven patients with aneurysms of the anterior communicating artery were treated under hypothermia. Three patients had excellent results. Three postoperative deaths occurred; two patients died in the hospital and one died of rerupture one month after operation. The poor-risk patients tolerated hypothermia well but it failed to improve the results in this group of patients. CONCL USIONS
At this time, a specific opinion cannot be given relative to the advisability of recommending induced hypothermia in all neurosurgical procedures. The time of the over-all procedure is lengthened because the anesthetic time is prolonged. The time of the operation itself is not lengthened. However, the relaxed brain, the relative avascularity and the early postoperative recovery associated with hypothermia should receive favorable consideration in prolonged and difficult neurosurgical procedures in which temporary occlusion of a major blood vessel may have to be carried out. Induced hypothermia appears to afford the surgeon more time to plan his surgical procedure and allows him to carry it out more expeditiously. The patient appears to have a greater reserve in the event of sudden hemorrhage. It is our opinion that these seriously ill patients were benefited by the use of induced hypothermia, because a more deliberate and radical attack could be carried out with fewer complications than had we attempted to carry out similar procedures under normothermic conditions with the usual anesthetic techniques.
1098
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
REFERENCES 1. Adams, J. E. and Wylie, E. J.: Value of Hypothermic and Arterial Occlusion in the Treatment of Intracranial Aneurysms. Surg., Gynec. & Obst. 108: 631~635 (May) 1959. 2. Albert, S. N., Spencer, W. A., Boling, J. S. and Thistlethwaite, J. R.: Hypothermia in the Management of the Poor-Risk Patient Undergoing Major Surgery. J.A.M.A. 163: 1435~1438 (April 20) 1957. 3. Alexander, Eben, Jr., Davis, C. H., Jr. and Kester, Nancy C.: Intracranial Aneurysms: Methods of Treatment: Value of Hypothermia in the Surgical Approach. A.M.A. Arch. Neurol. & Psychiat. 81: 684~692 (June) 1959. 4. Bigelow, W. G., Lindsay, W. K., Harrison, R. C., Gordon, R. A. and Greenwood, W. F.: Oxygen Transport and Utilization in Dogs at Low Body Temperatures. Am. J. Physiol. 160: 125~137 (Jan.) 1950. 5. Boerema, 1., Wildschut, A., Schmidt, W. J. H. and Broekhuysen, L.: Experimental Researches into Hypothermia as an Aid in Surgery of the Heart: Preliminary Communication. Arch. chiI'. neerl. 3: 25--34, 1951. 6. Bohm, E., Gordon, D., Tovi, D. and Persson, P. 0.: A New Device for Induced Hypothermia in Intracranial Surgery. Acta chiI'. scandinav. 113: 1-8, 1957. 7. Botterell, E. H., Lougheed, W. M., Morley, T. P. and Vandewater, S. L.: Hypothermia in the Surgical Treatment of Ruptured Intracranial Aneurysms. J. Neurosurg. 15: 4~18 (Jan.) 1958. 8. Botterell, E. H., Lougheed, W. M., Scott, J. W. and Vandewater, S. L.: Hypothermia, and Interruption of Carotid, or Carotid and Vertebral Circulation, in Surgical Management of Intracranial Aneurysms. J. Neurosurg. 13: 1~42 (Jan.) 1956. 9. Burrows, M. M., Dundee, J. W., Francis, 1. L., Lipton, S. and Sedzimer, C. B.: Hypothermia for Neurological Operations. Anaesthesia 11: 4~ 18 (Jan.) 1956. 10. Crossman, L. W.: The Status of Refrigeration for Amputations and for Tissue Preservation. Am. J. Surg. n. s . .91: 92~98 (Jan.) 1956. 11. Crossman, L. W. and Alien, F. M.: Principles of Surgical and Therapeutic Refrigeration. S. Clin. North America, April, 1945, pp. 361~370. 12. Drew, C. E., Keen, G. and Benazon, D. B.: Profound Hypothermia. Lancet 1: 745~747 (April 11) 1!J5!J. 13. Dripps, R. D.: Physiologic Problems in Anesthesia Related to Induced Hypothermia. S. Clin. North America, Dec., 1955, pp. 1573~1578. 14. Eckenhoff, J. K: The Physiology of Hypothermia. Bull. New York Acad. Med. 34: 297~302 (May) 1958. 15. Fairley, H. B., Wad dell, W. G. and Bigelow, W. G.: Hypothermia for Cardiovascular Surgery: Acidosis in the Rewarming Period. Brit. J. Anaesth. 2,9: 310~318 (July) 1957. 16. Fay, T.: Clinieal Report and Evaluation of Low Temperature in Treatment of Cancer. Proc. Interstate Post-Grad. M. A. North America 1941, pp. 292~297. 17. Fay, Temple and Smith, G. W.: Observations on Reflex Responses During Prolonged Periods of Human Refrigeration. Arch. Neurol. & Psychiat. 45: 215~ 222 (Feb.) 1941. 18. Field, John, Il, Fuhrman, F. A. and Martin, A. W.: Effect of Temperature on the Oxygen Consumption of Brain Tissue. J. N europhysiol. 7: 117~ 126 (March) 1944. 19. Fleming, P. R. and Muir, F. H.: Electrocardiographic Changes in Induced Hypothermia in Man. Brit. Heart J. 19: 5!)~66 (Jan.) 1957. 20. Gillingham, F. J.: The Management of Ruptured Intracranial Aneurysm. Ann. Roy. CoIl. Surgeons England 23: 89~117 (Aug.) 1958. 21. Goffrini, Piero and Bezzi, Eugenio: L'lpotermia generale controllata in chirurgia. Pisa, Omnia Medica, 1954, pp. !J!J~106. 22. Laborit, H.: Neuroplegia et hibernation artificielle. J. Internat. CoIl. Surgeons 24: 704~728 (Dec.) 1!J55.
Induced Hypothermia in Neurologic Conditions
1099
23. Lazorthes, G. and Campan, L.: Hypothermia in the Treatment of Craniocerebral Traumatism. J. Neurosurg. 15: 162-167 (March) 1958. 24. Lewis, F. J.: Hypothermia in Cardiac and General Surgery. Minnesota Med. 38: 77-81 (Feb.) 1955. 25. Logue, Valentine: Surgery in Spontaneous Subarachnoid Haemorrhage: Operative Treatment of Aneurysms on the Anterior Cerebral and Anterior Communieating Artery. Brit. M. J. 1: 473-479 (March 3) 1956. 26. Lundberg, Nils, Nielsen, K. C. and Nilsson, Eric: Deep Hypothermia in Intracranial Surgery. J. Neurosurg. 13: 235-247 (May) 1956. 27. McMurrey, J. D., Bernhard, W. F., Taren, J. A. and Bering, E. A., Jr.: Studies on Hypothermia in Monkeys. 1. The Effect of Hypothermia on the Prolongation of Permissible Time of Total Occlusion of the Afferent Circulation of the Brain. Surg., Gynec. & Obst. 102: 75-86 (Jan.) 1956. 28. Martin, J. T., Faulconer, Albert, Jr. and Bickford, R. G.: Electroencephalography in Anesthesiology. Anesthesiology 20: 359-376 (May-June) 1959. 29. Meyer, J. S. and Hunter, John: Effects of Hypothermia on Local Blood Flow and Metabolism During Cerebral Ischemia and Hypoxia. J. Neurosurg. 14: 210227 (March) 1957. 30. Petit-Dut&illis: Hibernation in Neurosurgery. Rev. path. gen. et comp. 669: 939,1955. 31. Pontius, R. G., Bloodwell, R. D., Cooley, D. A. and DeBakey, M. E.: The Use of Hypothermia in the Prevention of Brain Damage Following Temporary Arrest of the Cerebral Circulation: Experimental Observations. Am. Coli. Surgeons, Clin. Congo (40th), Proc. S. Forum 5: 224-228, 1954. 32. Pontius, R. G. and DeBakey, M. E.: Experimental and Clinical Observations on the Use of Hypothermia to Prevent Ischemic Damage to the Central Nervous System. The Physiology of Induced Hypothermia. NAS-NRC. Publication 451: 264-270, 1955. 33. Pool, J. L., Jacobson, Sherwood and Fletcher, T. A.: Cerebral VasospasmClinical and Experimental Evidence. J.A.M.A. 167: 1599-1601 (July 26) 1958. 34. Pool, J. L., Ransohoff, Joseph, Yahr, M. D. and Hammill, J. F.: Early Surgical Treatment of Aneurysms of the Circle of Willis. Neurology 9: 478-486 (July) 1959. 35. Pratt, G. H. and Collins, V. J.: Controlled Hypothermia as an Ancillary Surgical Procedure. S. Clin. North America, April, 1956, pp. 405-422. 3G. Ripstein, C. B., Friedgood, C. E. and Solomon, N.: Technique for Production of Hypothermia: Preliminary Report. Surgery 35: 98-103 (Jan.) 1954. 37. Rose, J. C., McDermott, T. F., Lilienfield, L. S., Porfido, F. A. and Kelley, R. T.: Cardiovascular Function in Hypothermic Anesthetized Man. Circulation 15: 512-517 (April) 1957. 38. Rosomoff, H. L.: Hypothermia and Cerebral Vascular Lesions. H. Experimental Middle Cerebral Artery Interruption Followed by the Induction of Hypothermia. Research Report: Project NM 007 081. 30.04 Naval Medical Research Institute. 39. Rosomoff, H. L. and Gilbert, Robert: Brain Volume and Cerebrospinal Fluid Pressure During Hypothermia. Am. J. Physiol. 183: ]9-22 (Oct.) 1955. 40. Rosomoff, H. L. and Holaday, D. A.: Cerebral Blood Flow and Cerebral Oxygen Consumption During Hypothermia. Am. J. Physiol. 179: 85-88 (Oct.) 1954. 41. Sedzimir, C. B. and Dundee, J. W.: Hypothermia in the Treatment of Cerebral Tumors. J. Neurosurg. 15: 199-206 (March) 1958. 42. Stone, H. H., MacKrell, T. N., Truter, Mary R., Donnelly, Celeste and Frobese, A. S.: The Effects of Lowered Body Temperature on the Cerebral Hemodynamics and Met&bolism of Man. Am. Coli. Surgeons, Clin. Congo (41st), Proc. S. Forum 6: 129-134, 1955. 43. Uihlein, Alfred and Lippert, R. G.: Unpublished data. 44. Vandewater, S. L., Lougheed, W. M., Scott, J. W. and Botterell, E. H.: Some
1100
ALFRED UIHLEIN, HOWARD TERRY, JR., JOHN MARTIN
Observations with the Use of Hypothermia in Neurosurgery. Anesth. & Analg. 37: 29-36 (Jan.-Feb.) 1958. 45. Virtue, R. W.: Hypothermic Anesthesia. Spring field, Illinois, Charles C Thomas, Publisher, 1955, 62 pp. 46. White, R. J., Uihlein, Alfred, and Grindlay, J. H.: The Design and Application of a Hydraulic Arterial Clamp for External Control of Cerebral Blood Flow. Am. ColI. Surgeons, Clin. Con/!:. (44th), Proc. S. Forum 9: 733-735, 1958.