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Use of Profound Hypothermia Induced by Surface Cooling in Open-Heart Surgery
Use of Profound Hypothennia Induced by Surface Cooling in Open-Heart Surgery Akihiko Matsumoto, M.D., Sunao Sato, M.D., Jiro Kondo, M.D., Junichi Kumada, M.D., Hisashi Goto, M.D., Mitsunori Kohno, M.D., Hiroto Matsumura, M.D., and Tatsuo Wada, M.D. ABSTRACT Profound hypothermia with bodysurface cooling for use in open-heart surgery is considered a difficult anesthetictechniquebecause of the problems of controlling ether anesthesia. This paper describes our hypothermia technique in detail, with emphasis on its particular usefulness in open-heart procedures in neonates and infants. The results are based on our experience with 281 consecutive patients. Guidelines for safe and effective performance of this technique were established on the basis of continuous monitoring of the electrocardiogram, electroencephalogram, and arterial blood pressure. We conclude from our experience that open-heart operation under profound hypothermia is a safe, effective, and extremely promising method.
Over the past ten years the results of open-heart operations for various cardiac conditions have shown marked improvement, largely due to the development of extracorporeal circulation as an auxiliary method during operation. Extracorporeal perfusion during open-heart procedures does have some disadvantages, in that a considerable amount of supplementary blood is required and a completely bloodless and motionless operative field is difficult to obtain. Therefore, since 1968 we have performed most openheart operations under hypothermia induced by body-surface cooling. The advantages of this method are: (1)minimal hemorrhage during the operative procedure; (2) a completely bloodless and motionless operative field; and (3) ease of postoperative respiratory care as well as a low incidence of pulmonary complications. In Japan, a study of this method was initiated by Watanabe in 1952 [9], and rapid development of From the Department of Surgery, Yokohama City University Hospital and School of Medicine, Yokohama, Japan. Accepted for publication Oct 13, 1975. Address reprint requests to Dr. Matsumoto, Department of Surgery, Division of Cardiovascular Surgery, Yokohama City University Hospital, Urafune-cho, Minami-ku, Yokohama, Japan 232.
330
the technique in line with his suggestions culminated in the first successful clinical applications in 1958 133. The purpose of this paper is to describe the technique we use for inducing profound hypothermia and to analyze in depth our results with 281 patients.
Materials and Methods Our 281 patients underwent open-heart operations under profound hypothermia induced by body-surface cooling in Yokohama City University Hospital from January, 1968, through December, 1974 (Table).Ages ranged from 1month to 28 years with a mean of 4.6 years. Infants and children are good candidates for this method, and pediatric patients predominate in our series.
Anesthesia The method of anesthesia has been reported elsewhere [5]. As a rule, however, we follow the method advocated by Okamura [3, 71, which will be described in detail. Intramuscular injections of triflupromazine, 0.15 mg per kilogram of body weight, and Pethilorfan (pethidine and levallorphan), 0.5 to 1.0 mglkg, are given 1%hours prior to initiation of anesthesia. One hour prior to induction, hydroxyzine, 0.5 to 1.0 mglkg, and atropine, 0.005 to 0.007 mg/kg, are administered intramuscularly. Triflupromazine, Pethilorfan, and hydroxyzine are repeated in the same dosages 30 minutes prior to the onset of anesthesia. In infants and small children, ketamine hydrochloride, 4 mglkg, is given intramuscularlyfor induction of anesthesia, while in adults 300 to 400 mg of thiopental sodium is administered intravenously. Finally, 20 to 30 minutes prior to anesthesia induction and the start of body cooling, another dose of triflupromazine, 0.5 mglkg, is given intravenously.
331
Matsumoto et al: Profound Hypothermia Induced by Surface Cooling
Patients Undergoing Open-Heart Operations Using Profound Hypothermia with Surface Cooling No. of Patients Anomaly VSD VSD with PH VSD with PS VSD & ASD VSD, ASD, & PS VSD & PDA VSD & PDA with PH ASD PS PS with ASD ECCD TAPVR TIF BVRV (double-outlet) PA Truncus arteriosus Coarctation complex A1 VSD with AI MI Miscellaneous Total
1968
1969 8 2
1970 7 9 (1) 2
1971
1972
1973
22 8
1 1
1 16 (1)
38 (7)
59 (9)
50 (2)
38 (4)
1974
Total Patients
Mortality (%)
64 (1) 45 (3) 13 (1) 2 1 1 5 52 8 14 (1) 3 (2) 4 (3) 53 (17) 3 (2) 1 (1) 1 (1) 4 (3) 1 1 2 3 (2)
1.6 6.7 7.7 0 0 0 0 0 0 7.1 66.7 75 32 66.7 100 100 75 0 0 0 66.7
281 (37)
13.2
Numbers in parentheses represent deaths VSD = ventricular septal defect;PH = pulmonary hypertension;PS = pulmonary stenosis;ASD = atrial septal defect; PDA = patent ductus arteriosus; ECCD = endocardia1cushion defect; TAPVR = total anomalous pulmonary venous return; TIF = tetralogy of Fallot; BVRV = origin of both great vessels from the right ventricle; PA = pulmonary atresia; AI = aortic insufficiency; MI = mitral insufficiency.
In order to prevent possible blood sludging during hypothermia, 15 mYkg of lowmolecular-weight dextran is instilled by intravenous drip during the process of cooling. At the time of occlusion of the major vessels, Young’s solution,* 0.8 to 1.0 mYkg but not to exceed 20 ml at one time, is injected into the aortic root to induce cardiac standstill. The aortic clamp is released and the cardiac resuscitation solution,t 1.0 mUkg but not to exceed 20 ml at one time, is injected into the left ventricle
through the apex. Heparin, 1.5 mglkg, is administered when the esophageal temperature falls below 30°C. Protamine sulfate, 1.5 mglkg, is usually given when the body temperature has returned to approximately 27°C and sinus rhythm has been restored. Following endotracheal intubation, rapid ether inhalation is started within a closed circuit. The patient is thus quickly brought into Stage 111, Plane I, status (the lightest stage of surgical anesthesia) within 3 to 5 minutes of ether inhalation. Ether inhalation can be con*Young’ssolution: 0.81 gm of sodium citrate and 2.46 gm of tinued by way of the patient’s spontaneous remagnesium sulfate dissolved in 100 ml of water with pH spiration. The patient should reach Stage 111, adjusted to 7.4. Plane 111, status (deep anesthesia) and remain tCardiac resuscitation solution: 10 ml of 20% glucose in water, 100 ml of 2% CaC12,and 1.0 ml of 0.1% norepineph- there throughout the course of hypothermia. Though the relationship between the ether rine.
332 The Annals of Thoracic Surgery Vol 22 No 4 October 1976
inhalation dosage and the decline in body temperature cannot be strictly defined, 2.0 cdkg of ether inhaled at 30"C, 2.5 cclkg at 25"C, and 3.0 cclkg upon reaching the target body temperature are recommended, with further adjustment thereafter. Due to the inevitable leakage of ether from the anesthesia machine, 3.5 to 4.0 cdkg is sometimes required at the final stage. We calculate the precise dosage of ether to be inhaled on the basis of changes in arterial blood pressure, the electrocardiogram, and the electroencephalogram. During anesthesia, the following are monitored either continuously or intermittently: electroencephalogram (bipolar frontal leads); electrocardiogram (mostly lead II); arterial blood pressure (femoral or brachial artery); central venous pressure; oxygen tension ( P a ) ; carbon dioxide tension (PcQ); pH; and hematocrit for both arterial and venous blood. Blood gas analysis is carried out using the Astrup radiometer.*
Hypothermia Technique It should be noted that the mode of anesthesia described is designed specifically for profound hypothermia in connection with an open-heart operation. Cooling is usually started when the anesthesia status reaches Stage 111, Plane I1 (moderate surgical anesthesia); the time required to reach this state is about 10 minutes. The conventional dose of ether inhaled initially from intubation to the beginning of cooling is 1.0 cclkg. Subsequent doses should be titrated according to the method previously described. The usual maintenance dose of ether is in the range of 3.0 to 3.5 cdkg. During cooling, the speed of ether inhalation must be carefully adjusted in order to avoid extremely slow cardiac rhythm or standstill. As the target body temperature of 20°C is approached, the patient is removed from the ice-water bath at 23°C to avoid further cooling. Occasionally we have worked with a patient at a body temperature of slightly over 20°C. The heart rate and rhythm in these patients remain favorable, and no adverse change is noted even when the heart is palpated directly or an intracardiac maneuver 'Astrup Manufacturing Co, Copenhagen, Denmark.
is carried out. We believe this is due to the unique antiarrhythmic properties of ether. As shown in Figure 1, arterial pressure and pulse rate decrease steadily along with the fall in body temperature. It should be noted that despite the decline in arterial pressure, adequate pulse pressure is maintained. In the presence of satisfactory peripheral circulation as well as sufficient pulse pressure, complications such as postoperative cerebral damage due to circulatory insufficiency are avoided. Following occlusion of the superior and inferior venae cavae, sufficient manual pressure is applied to the lung so that blood in the heart and lungs can be diverted to the systemic circulation. The aorta is then clamped. This is followed by an injection of 0.8 mYkg of Young's solution into the root of the aorta. As soon as cardiac standstill is achieved, the intracardiac procedure can be started. At cardiotomy, the small amount of blood remaining in the cardiac chambers is suctioned out; it should be retransfused to the patient following resuscitation, thus minimizing the amount of new blood needed. When the operation nears completion, warm water (about 45°C) is poured into the bathtub for reversion of the body temperature. At the end of the procedure the platform is kept lowered, and the patient is warmed while floating in warm water. Air in the cardiac cavity must be completely removed before the aortic clamp is released. After several applications of cardiac massage, 1 mYkg of the cardiac resuscitating agent is introduced through the apex into the left ventricle. At this point the assistant compresses the ascending aorta to ensure effective inflow of the agent through the coronary arteries. Aortic occlusion, including cardiac anoxia, may be continued safely for up to 60 minutes at 20°C or 30 minutes at 25°C according to our experience. During rewarming, the blood drawn from the cardiac cavities during hypothermia is transfused back to the patient. At the actual operation little hemorrhage occurs, and therefore retransfusion of the patient's own blood frequently suffices for blood replacement. Rewarming usually proceeds in a manner analogous to the process of cooling. Regular sinus rhythm is reestablished at around 30°C. The rewarming process is terminated upon reaching the target temperature of 35" to 36°C. Since optimal rewarming can
333 Matsumoto et al: Profound Hypothermia Induced by Surface Cooling
0
0 PH Pa02
PaCO, BE
7.40 7.38 7.40 520 460 480 24 30 28 -5.0 -7.5 -8.0
7.32 7.43 75 300 45 27 -3.0 -5.5 A
0
0 7.00 450 67 -16
7.23 550 30 -15
@ Hr 7.32 40 0 30 -9.0
7.30 420 26 -11
A A
180. 160
140
A A A
A A
body temperature
A
A
Circulatory
Cardiac
120
heart r a t e
I00 80
60 40 20
Fig 1. Typical course of an open-heart operation under profound hypothermia. Alterations in physiological variables prior to, during, and immediately after the procedure are shown. The patient is an 11-month-old boy weighing5,700gm who had a ventricular septa1 defect and severe pulmonary hypertension. (BE= base excess; LMWD = low-molecular-weight dextran.)
usually be achieved near the end of the operation, anesthesia need not be unduly prolonged. An additional advantage of this type of hypothermia lies in the relative ease of postoperative respiratory control. Spontaneous respiration resumes almost immediately after the operation, and we have seldom encountered a patient who required postoperative ventilation.
Results There were 37 operative deaths (13.1%) among the 281 patients undergoing open-heart operations using profound hypothermia. Among the patients operated upon in 1968 there were some whose cardiac resuscitation proved difficult. In 3 patients cerebral damage ensued, probably due to lack of refinement in the hypothermia technique [5]. With subsequent improvement in the method, however, these complications subsided, and we have encountered none since 1970. As a rule, we induced intensive hemodilution with low-molecular-weight dextran in order to
- 37 - 35 - 33
- 31
A A A
- 39
blood pressure
- 29 - 27
- 25 - 23 - 21 - 19 - 17
prevent the sharp rise in blood viscosity associated with sludging of peripheral blood which accompanies the fall in body temperature. Accordingly, hematocrit values usually stayed between 30 and 35% throughout the course. This was true even in patients with marked cyanosis. Blood gases and acid-base balance were measured at 38"C, and Paq showed considerable variation during the course of anesthesia. It is difficult to draw any conclusions from our blood gas data since these variables are prone to subtle changes, depending on the basic disease and the degree of anesthesia. Generally speaking, however, the average Pa% during operation was found to be in the neighborhood of 400 mm Hg in patients with a left-to-right shunt. As cooling progresses, it is natural for oxygen consumption to decrease, resulting in a rise in Paq; a reverse trend should be seen during the rewarming process. In actuality, however, Pa% remained continually higher than preoperative values because correction of the cardiac anomaly had already been completed at about the time rewarming was achieved. Figures 2 and 3 show the changes in Pac% and pH with alterations in body temperature. The Pacq stayed around 40 mm Hg with a transient rise of slight degree at around 30°C, which was followed by a gradual decrease thereafter. A close relationship was evident between Pa&,
334 The Annals of Thoracic Surgery Vol 22 No 4 October 1976
mmHg VSD 17 VSDZPH 10
9 16
VSDZPH
42
38
34
30 I
l
l
35
30
25
T
I
I
1
I
25Warming 30 35 Cooling Circulatory Arrest
1
1
1
1
1
Cooling Warming Circulatory Arrest
Fig2. Changes in Pa,,, duringanesthesia. (A) Average Pacoz values in 52 patients. (B)Paco, in various cardiac conditions. (VSD= ventricular septal defect; PH = pulmonary hypertension; ASD = atrial septal defect; T/F= tetralogy of Fallot.)
17 VSD VSDCPH 10 ASD 9 T/F 16
7.4
7.3
7.2
7.1
7.0
4
35
30
25
Warming Cooling Circulatory Arrest
Figs. Changes in pH during anesthesia (measured at 38°C). (A)Average values in 52 patients. ( B ) Values in various cardiac conditions. (Abbreviations same as in Figure2.)
35
30
25
t
Cooling 25Warming 30 35 Circulatory Arrest
335 Matsumoto et al: Profound Hypothermia Induced by Surface Cooling
Pacoz, and the degree of anesthesia. Low values were sometimes obtained when hyperventilation was observed during the course of anesthesia. As to pH and base excess, the former remained at around 7.30 during the cooling process up to the time of aortic occlusion, while the latter showed a slight decrease (Fig 4). It is not yet known whether these changes are directly related to the effect of hypothermia or to the pharmacological action of ether. When rewarming was begun following the release of aortic occlusion, the Pacq showed a transient rise and pH fell suddenly, indicating the development of acidosis. It was observed that due to hyperventilation, Pacoz values occasionally declined to a slightly lower level than in the cooling process but returned to nearly normal limits within several hours after completion of the operation. It is to be emphasized that keeping the Paco, as low as possible (20 to 30 mm Hg) by means of hyperventilation is mandatory in order to hold pH within the physiological range. During anesthesia, and especially in the process of rewarming, the heartbeat recovered favorably as the pH returned closer to normal values. Cardiac resuscitation was usually easy, and no major arrhythmia was encountered. Fig4. Changes in base excess during anesthesia (measured at 38°C). (A)Average value in 52 patients. (B)Values in various cardiac conditions. (Abbreviations same as in Figure 2.)
Base excess was usually negative not only during rewarming but also thereafter, which may indicate that metabolic acidosis was present. Nevertheless, no special correction was required in most of the patients. Return to normal values was generally noted several hours after operation, with the patient who had the longest delay requiring a day for recovery (see Fig 4). Some variations were noted in serum electrolytes. The average preoperative value for sodium was 136 mEqlL; potassium, 4.3 mEq/L; and chlorine, 106 mEqlL. During the cooling process serum potassium decreased slightly in most patients, though occasionally it fell as low as 2.6 mEq/L just prior to the institution of cardiac anoxia. This trend, however, would reverse itself, and a gradual rise would begin during the process of rewarming so that at the completion of rewarming preoperative values were usually restored. Sodium and chlorine showed little change, even immediately before the cardiac standstill. After cooling was begun, electroencephalographic waves (from bipolar frontal leads) became gradually slower in proportion to the fall in body temperature, with a characteristic decrease of rapid waves as well as a decline in amplitude. Immediately before aortic occlusion and cardioplegia, the EEG was frequently observed to be flattened, and occasionally it completely disappeared. Excessively fast inhalation of ether caused rapid suppression of the EEG; the same trend was occasionally seen with a relatively VSD 17 VSDZPH 10 ASD 9 T/F 16
- 5 -
-
10 -
-
15
-
-20I
,
,
35 30' 25'
1
1
1
1
25' 30' 35'
1 1
Cooling Warming Circulatory Arrest 2 H r s A f t e r Surgery
1
,
35' 30'
I
,
I
25'
Cooling Warming Circulatory Arrest
,
336 The Annals of Thoracic Surgery Vol 22 No 4 October 1976
high body temperature. In this regard the EEG can serve as an index of the depth of anesthesia, the degree of cerebral hypoxia, and the state of the autonomic nervous system. As body temperature fell, prolonged P-Q and R-R intervals in the electrocardiogram indicated the onset of bradycardia. As long as anesthesia was adequate, sinus rhythm was usually maintained and would be until the time of circulatory occlusion. Supraventricular arrhythmia or atrial fibrillation might occasionally supervene, but in our experience these were always due to inadequate anesthesia, and sinus rhythm was usually restored with rapid inhalation of a small amount of ether. No remarkable changes were noted in the S-T segment and T wave. If bradycardia persists or restoration of sinus rhythm is delayed once resuscitation has begun, atrioventricular block should be considered. Right bundle-branch block can also appear after the incision has been made in the right ventricle. These abnormalities should be detected as early as possible and treated appropriately to ensure an uneventful postoperative course.
pulse rate parallel to a gradual fall in the body temperature can thus be ensured. If the anesthetic is given in insufficient quantities during the cooling process, peripheral vascular contraction is apt to occur, resulting in extensive shivering and thus imposing excessive stress on the patient that might preclude continuation of anesthesia. In order to prevent untoward occurrences during the cooling process, adequate titration of ether as well as the use of autonomic blocking agents with peripheral vasodilating action is of paramount importance. Excessively deep ether anesthesia, however, can cause peripheral circulatory insufficiency, suppression of cardiac function as manifested by an abnormal ECG, or profound hypotension. This makes subsequent cooling and resuscitation extremely difficult. It may also cause irreversible cerebral damage, and therefore one must be extremely cautious not to give an excessive amount of ether. Ether also has the property of concentrating blood. Hypothermia further exacerbates this effect, and complications such as sludging of the blood may occur. This, however, can be effecComment tively prevented by administration of lowEther anesthesia is widely used in profound molecular-weight dextran and heparin. Oxygen hypothermia despite its explosive properties consumption decreases markedly during and such disadvantages as its tendency to raise hypothermia, and cerebral damage, when it secretions in the airway. This is mainly because does occur, is believed to be due to the ether’s of the fact that it possesses a unique antiar- effect on both blood concentration and coagularhythmic effect. Ether can also inhibit cardiac bility rather than to tissue hypoxia secondary to function, however, and it is essential to keep the hypothermia and the operative procedure [l]. dose within a narrow therapeutic range in While many studies are available on the status which only the antiarrhythmic effect is ex- of acid-base balance during hypothermia, the pressed and no suppression of cardiac function results are not uniform. In our series base excess is exhibited. Since the body temperature of was often negative at the onset of anesthesia, human beings, who are homeothermic animals, which might have been partially due to the cannot be lowered below 20°C without the use of pharmacological action of ether, and it tended to anesthesia, an investigation of the potential in- decrease further with cooling, reaching as low as fluence of anesthesia upon the pathophysiology -10 mEqlL. Immediately after release of aortic of hypothermia is badly needed. At present, occlusion, however, a reversal of this condition however, neither the basic physiology nor the occurred and profound acidosis developed. It is biochemistry of hypothermia is clearly under- apparent that this was due to the outpouring stood, and this is why anesthesia under and subsequent circulation of acid substances hypothermia is accepted with much hesitancy. that had accumulated in the tissues because of In order to maintain desirable circulatory anaerobic metabolism during circulatory occluhemodynamics during hypothermic anesthesia, sion. This acidosis was transient, and the meit appears that skillful induction of the anes- tabolism stabilized quickly during rewarming. Nearly normal pH values were usually obthesia is most important. A gradual decline in arterial blood pressure and a smooth decrease of tained relatively early in the postoperative
337
Matsumoto et al: Profound Hypothermia Induced by Surface Cooling
period. Isayama [2] has pointed out that acidosis in hypothermia is not as important as it had been assumed to be and concluded that it may be connected with the nature of hypothermia per se. On the other hand, as pointed out by Mohri and co-workers [6], a more favorable anesthetic course is obtained if acidosis can be prevented before and after aortic occlusion. This is usually achieved by keeping Pat% low with induced hyperventilation and also by maintaining pH values at a rather high level, around 7.80, throughout the course. In any case, acid-base balance under hypothermia needs to be investigated further in light of the complex metabolic changes that take place. Many reports are available concerning electrolyte metabolism during hypothermia. In each, electrolyte concentration does not vary widely, and its relationship with hypothermia is not clearly established as yet [81. In our series sodium and chlorine showed few changes, and potassium was either at the lower limit of normal or slightly below it. The lowest value was encountered either at a body temperature of 24" to 25°C or at the time of circulatory occlusion. It is generally believed that changes in serum potassium level are directly related to the degree of fall in body temperature. However, the significance of this observation is as yet poorly understood. The electroencephalogram has long been used to evaluate the depth of anesthesia. Among anesthetic agents, ether has been studied most extensively for its effect on the EEG. As the anesthesia is deepened with ether, EEG amplitude i s usually increased, with a concomitant decrease in the cycle. Such a relationship is quite closely correlated, and EEG changes precisely reflect the concentration of ether in the arterial blood. In hypothermia with deep ether anesthesia the EEG does not disappear until the point immediately before aortic occlusion. Once ischemia is instituted, however, the EEG disappears within several seconds and reappears only when the body temperature rises above 30°C. There is a rapid recovery to normal after the temperature has reached 35°C. The electrocardiogram reflects cardiac status and depth of anesthesia. When anesthesia is too deep, myocardial suppression occurs, leading to hypotension; ECG abnormalities are usually
noted under such circumstances. The anesthesia should therefore be controlled within a very narrow range, and cooling should be started at the proper time; the ECG is an informative guide in determining this range. A favorable cardiac condition during the cooling process is characterized by a sustained, regular sinus rhythm with minimal S-T and T-wave changes. According to Okamura [71, ventricular fibrillation, along with other kinds of dysrhythmias, sometimes appears during hypothermia. In most cases this is due to an increase in myocardial irritability. In our experience, however, arrhythmias in hypothermia are usually manifested in the form of supraventricular rhythm disturbances, particularly atrial fibrillation or conduction abnormalities such as atrioventricular block. We have seen no instances of ventricular fibrillation.
References 1. Bjork VO, Holmdahl MH: The oxygen consumption in man under deep hypothermia and the safe period of circulatory arrest. J Thorac Cardiovasc Surg 42:392, 1961 2. Isayama T: Experimental studies on profound hypothermia from the viewpoint of acid-base balance in whole blood. J Jpn Surg SOC73:397, 1972 3. Ishikawa Y, Okamura H: Grenzen fur die Wieberbelebung bei Operation am offenen Herzen unter tiefer Hypothermia. Langenbecks Arch Chir 289:232, 1958 4. Matsumoto A, Nishi H, Sat0 S, et al: Studies of cerebral damage after open heart surgery using profound hypothermia with surface cooling: long-term follow-up studies. Yokohama Med J 23:111, 1972 5. Matsumoto A, Sat0 S, Kondo J, et al: Open heart surgery in neonates and infants using profound hypothermia with surface cooling. Cine seminar presented at the 22nd Annual Meeting of the American College of Cardiology, San Francisco, Feb 16, 1973 6. Mohri H, Dillard DH, Crawford EW, et al: Method of surface-induced deep hypothermia for open heart surgery in infants. J Thorac Cardiovasc Surg 58:262, 1969 7. Okamura H: Inhalation anesthesia for simple deep hypothermia induced by surface cooling. Med J Osaka Univ 20:29, 1969 8. Rittenhouse EA, Mohri H, Merendino KA:Studies of carbohydrate metabolism with prolonged circulatory occlusion. Surgery 67:995, 1970 9. Watanabe A: Experimental study of profound hypothermia induced with surface cooling. J Jpn Surg SOC 58:1675, 1958
Over the past ten years the results of open-heart operations for various cardiac conditions have shown marked improvement, largely due to the development of extracorporeal circulation as an auxiliary method during operation. Extracorporeal perfusion during open-heart procedures does have some disadvantages, in that a considerable amount of supplementary blood is required and a completely bloodless and motionless operative field is difficult to obtain. Therefore, since 1968 we have performed most openheart operations under hypothermia induced by body-surface cooling. The advantages of this method are: (1)minimal hemorrhage during the operative procedure; (2) a completely bloodless and motionless operative field; and (3) ease of postoperative respiratory care as well as a low incidence of pulmonary complications. In Japan, a study of this method was initiated by Watanabe in 1952 [9], and rapid development of From the Department of Surgery, Yokohama City University Hospital and School of Medicine, Yokohama, Japan. Accepted for publication Oct 13, 1975. Address reprint requests to Dr. Matsumoto, Department of Surgery, Division of Cardiovascular Surgery, Yokohama City University Hospital, Urafune-cho, Minami-ku, Yokohama, Japan 232.
330
the technique in line with his suggestions culminated in the first successful clinical applications in 1958 133. The purpose of this paper is to describe the technique we use for inducing profound hypothermia and to analyze in depth our results with 281 patients.
Materials and Methods Our 281 patients underwent open-heart operations under profound hypothermia induced by body-surface cooling in Yokohama City University Hospital from January, 1968, through December, 1974 (Table).Ages ranged from 1month to 28 years with a mean of 4.6 years. Infants and children are good candidates for this method, and pediatric patients predominate in our series.
Anesthesia The method of anesthesia has been reported elsewhere [5]. As a rule, however, we follow the method advocated by Okamura [3, 71, which will be described in detail. Intramuscular injections of triflupromazine, 0.15 mg per kilogram of body weight, and Pethilorfan (pethidine and levallorphan), 0.5 to 1.0 mglkg, are given 1%hours prior to initiation of anesthesia. One hour prior to induction, hydroxyzine, 0.5 to 1.0 mglkg, and atropine, 0.005 to 0.007 mg/kg, are administered intramuscularly. Triflupromazine, Pethilorfan, and hydroxyzine are repeated in the same dosages 30 minutes prior to the onset of anesthesia. In infants and small children, ketamine hydrochloride, 4 mglkg, is given intramuscularlyfor induction of anesthesia, while in adults 300 to 400 mg of thiopental sodium is administered intravenously. Finally, 20 to 30 minutes prior to anesthesia induction and the start of body cooling, another dose of triflupromazine, 0.5 mglkg, is given intravenously.
331
Matsumoto et al: Profound Hypothermia Induced by Surface Cooling
Patients Undergoing Open-Heart Operations Using Profound Hypothermia with Surface Cooling No. of Patients Anomaly VSD VSD with PH VSD with PS VSD & ASD VSD, ASD, & PS VSD & PDA VSD & PDA with PH ASD PS PS with ASD ECCD TAPVR TIF BVRV (double-outlet) PA Truncus arteriosus Coarctation complex A1 VSD with AI MI Miscellaneous Total
1968
1969 8 2
1970 7 9 (1) 2
1971
1972
1973
22 8
1 1
1 16 (1)
38 (7)
59 (9)
50 (2)
38 (4)
1974
Total Patients
Mortality (%)
64 (1) 45 (3) 13 (1) 2 1 1 5 52 8 14 (1) 3 (2) 4 (3) 53 (17) 3 (2) 1 (1) 1 (1) 4 (3) 1 1 2 3 (2)
1.6 6.7 7.7 0 0 0 0 0 0 7.1 66.7 75 32 66.7 100 100 75 0 0 0 66.7
281 (37)
13.2
Numbers in parentheses represent deaths VSD = ventricular septal defect;PH = pulmonary hypertension;PS = pulmonary stenosis;ASD = atrial septal defect; PDA = patent ductus arteriosus; ECCD = endocardia1cushion defect; TAPVR = total anomalous pulmonary venous return; TIF = tetralogy of Fallot; BVRV = origin of both great vessels from the right ventricle; PA = pulmonary atresia; AI = aortic insufficiency; MI = mitral insufficiency.
In order to prevent possible blood sludging during hypothermia, 15 mYkg of lowmolecular-weight dextran is instilled by intravenous drip during the process of cooling. At the time of occlusion of the major vessels, Young’s solution,* 0.8 to 1.0 mYkg but not to exceed 20 ml at one time, is injected into the aortic root to induce cardiac standstill. The aortic clamp is released and the cardiac resuscitation solution,t 1.0 mUkg but not to exceed 20 ml at one time, is injected into the left ventricle
through the apex. Heparin, 1.5 mglkg, is administered when the esophageal temperature falls below 30°C. Protamine sulfate, 1.5 mglkg, is usually given when the body temperature has returned to approximately 27°C and sinus rhythm has been restored. Following endotracheal intubation, rapid ether inhalation is started within a closed circuit. The patient is thus quickly brought into Stage 111, Plane I, status (the lightest stage of surgical anesthesia) within 3 to 5 minutes of ether inhalation. Ether inhalation can be con*Young’ssolution: 0.81 gm of sodium citrate and 2.46 gm of tinued by way of the patient’s spontaneous remagnesium sulfate dissolved in 100 ml of water with pH spiration. The patient should reach Stage 111, adjusted to 7.4. Plane 111, status (deep anesthesia) and remain tCardiac resuscitation solution: 10 ml of 20% glucose in water, 100 ml of 2% CaC12,and 1.0 ml of 0.1% norepineph- there throughout the course of hypothermia. Though the relationship between the ether rine.
332 The Annals of Thoracic Surgery Vol 22 No 4 October 1976
inhalation dosage and the decline in body temperature cannot be strictly defined, 2.0 cdkg of ether inhaled at 30"C, 2.5 cclkg at 25"C, and 3.0 cclkg upon reaching the target body temperature are recommended, with further adjustment thereafter. Due to the inevitable leakage of ether from the anesthesia machine, 3.5 to 4.0 cdkg is sometimes required at the final stage. We calculate the precise dosage of ether to be inhaled on the basis of changes in arterial blood pressure, the electrocardiogram, and the electroencephalogram. During anesthesia, the following are monitored either continuously or intermittently: electroencephalogram (bipolar frontal leads); electrocardiogram (mostly lead II); arterial blood pressure (femoral or brachial artery); central venous pressure; oxygen tension ( P a ) ; carbon dioxide tension (PcQ); pH; and hematocrit for both arterial and venous blood. Blood gas analysis is carried out using the Astrup radiometer.*
Hypothermia Technique It should be noted that the mode of anesthesia described is designed specifically for profound hypothermia in connection with an open-heart operation. Cooling is usually started when the anesthesia status reaches Stage 111, Plane I1 (moderate surgical anesthesia); the time required to reach this state is about 10 minutes. The conventional dose of ether inhaled initially from intubation to the beginning of cooling is 1.0 cclkg. Subsequent doses should be titrated according to the method previously described. The usual maintenance dose of ether is in the range of 3.0 to 3.5 cdkg. During cooling, the speed of ether inhalation must be carefully adjusted in order to avoid extremely slow cardiac rhythm or standstill. As the target body temperature of 20°C is approached, the patient is removed from the ice-water bath at 23°C to avoid further cooling. Occasionally we have worked with a patient at a body temperature of slightly over 20°C. The heart rate and rhythm in these patients remain favorable, and no adverse change is noted even when the heart is palpated directly or an intracardiac maneuver 'Astrup Manufacturing Co, Copenhagen, Denmark.
is carried out. We believe this is due to the unique antiarrhythmic properties of ether. As shown in Figure 1, arterial pressure and pulse rate decrease steadily along with the fall in body temperature. It should be noted that despite the decline in arterial pressure, adequate pulse pressure is maintained. In the presence of satisfactory peripheral circulation as well as sufficient pulse pressure, complications such as postoperative cerebral damage due to circulatory insufficiency are avoided. Following occlusion of the superior and inferior venae cavae, sufficient manual pressure is applied to the lung so that blood in the heart and lungs can be diverted to the systemic circulation. The aorta is then clamped. This is followed by an injection of 0.8 mYkg of Young's solution into the root of the aorta. As soon as cardiac standstill is achieved, the intracardiac procedure can be started. At cardiotomy, the small amount of blood remaining in the cardiac chambers is suctioned out; it should be retransfused to the patient following resuscitation, thus minimizing the amount of new blood needed. When the operation nears completion, warm water (about 45°C) is poured into the bathtub for reversion of the body temperature. At the end of the procedure the platform is kept lowered, and the patient is warmed while floating in warm water. Air in the cardiac cavity must be completely removed before the aortic clamp is released. After several applications of cardiac massage, 1 mYkg of the cardiac resuscitating agent is introduced through the apex into the left ventricle. At this point the assistant compresses the ascending aorta to ensure effective inflow of the agent through the coronary arteries. Aortic occlusion, including cardiac anoxia, may be continued safely for up to 60 minutes at 20°C or 30 minutes at 25°C according to our experience. During rewarming, the blood drawn from the cardiac cavities during hypothermia is transfused back to the patient. At the actual operation little hemorrhage occurs, and therefore retransfusion of the patient's own blood frequently suffices for blood replacement. Rewarming usually proceeds in a manner analogous to the process of cooling. Regular sinus rhythm is reestablished at around 30°C. The rewarming process is terminated upon reaching the target temperature of 35" to 36°C. Since optimal rewarming can
333 Matsumoto et al: Profound Hypothermia Induced by Surface Cooling
0
0 PH Pa02
PaCO, BE
7.40 7.38 7.40 520 460 480 24 30 28 -5.0 -7.5 -8.0
7.32 7.43 75 300 45 27 -3.0 -5.5 A
0
0 7.00 450 67 -16
7.23 550 30 -15
@ Hr 7.32 40 0 30 -9.0
7.30 420 26 -11
A A
180. 160
140
A A A
A A
body temperature
A
A
Circulatory
Cardiac
120
heart r a t e
I00 80
60 40 20
Fig 1. Typical course of an open-heart operation under profound hypothermia. Alterations in physiological variables prior to, during, and immediately after the procedure are shown. The patient is an 11-month-old boy weighing5,700gm who had a ventricular septa1 defect and severe pulmonary hypertension. (BE= base excess; LMWD = low-molecular-weight dextran.)
usually be achieved near the end of the operation, anesthesia need not be unduly prolonged. An additional advantage of this type of hypothermia lies in the relative ease of postoperative respiratory control. Spontaneous respiration resumes almost immediately after the operation, and we have seldom encountered a patient who required postoperative ventilation.
Results There were 37 operative deaths (13.1%) among the 281 patients undergoing open-heart operations using profound hypothermia. Among the patients operated upon in 1968 there were some whose cardiac resuscitation proved difficult. In 3 patients cerebral damage ensued, probably due to lack of refinement in the hypothermia technique [5]. With subsequent improvement in the method, however, these complications subsided, and we have encountered none since 1970. As a rule, we induced intensive hemodilution with low-molecular-weight dextran in order to
- 37 - 35 - 33
- 31
A A A
- 39
blood pressure
- 29 - 27
- 25 - 23 - 21 - 19 - 17
prevent the sharp rise in blood viscosity associated with sludging of peripheral blood which accompanies the fall in body temperature. Accordingly, hematocrit values usually stayed between 30 and 35% throughout the course. This was true even in patients with marked cyanosis. Blood gases and acid-base balance were measured at 38"C, and Paq showed considerable variation during the course of anesthesia. It is difficult to draw any conclusions from our blood gas data since these variables are prone to subtle changes, depending on the basic disease and the degree of anesthesia. Generally speaking, however, the average Pa% during operation was found to be in the neighborhood of 400 mm Hg in patients with a left-to-right shunt. As cooling progresses, it is natural for oxygen consumption to decrease, resulting in a rise in Paq; a reverse trend should be seen during the rewarming process. In actuality, however, Pa% remained continually higher than preoperative values because correction of the cardiac anomaly had already been completed at about the time rewarming was achieved. Figures 2 and 3 show the changes in Pac% and pH with alterations in body temperature. The Pacq stayed around 40 mm Hg with a transient rise of slight degree at around 30°C, which was followed by a gradual decrease thereafter. A close relationship was evident between Pa&,
334 The Annals of Thoracic Surgery Vol 22 No 4 October 1976
mmHg VSD 17 VSDZPH 10
9 16
VSDZPH
42
38
34
30 I
l
l
35
30
25
T
I
I
1
I
25Warming 30 35 Cooling Circulatory Arrest
1
1
1
1
1
Cooling Warming Circulatory Arrest
Fig2. Changes in Pa,,, duringanesthesia. (A) Average Pacoz values in 52 patients. (B)Paco, in various cardiac conditions. (VSD= ventricular septal defect; PH = pulmonary hypertension; ASD = atrial septal defect; T/F= tetralogy of Fallot.)
17 VSD VSDCPH 10 ASD 9 T/F 16
7.4
7.3
7.2
7.1
7.0
4
35
30
25
Warming Cooling Circulatory Arrest
Figs. Changes in pH during anesthesia (measured at 38°C). (A)Average values in 52 patients. ( B ) Values in various cardiac conditions. (Abbreviations same as in Figure2.)
35
30
25
t
Cooling 25Warming 30 35 Circulatory Arrest
335 Matsumoto et al: Profound Hypothermia Induced by Surface Cooling
Pacoz, and the degree of anesthesia. Low values were sometimes obtained when hyperventilation was observed during the course of anesthesia. As to pH and base excess, the former remained at around 7.30 during the cooling process up to the time of aortic occlusion, while the latter showed a slight decrease (Fig 4). It is not yet known whether these changes are directly related to the effect of hypothermia or to the pharmacological action of ether. When rewarming was begun following the release of aortic occlusion, the Pacq showed a transient rise and pH fell suddenly, indicating the development of acidosis. It was observed that due to hyperventilation, Pacoz values occasionally declined to a slightly lower level than in the cooling process but returned to nearly normal limits within several hours after completion of the operation. It is to be emphasized that keeping the Paco, as low as possible (20 to 30 mm Hg) by means of hyperventilation is mandatory in order to hold pH within the physiological range. During anesthesia, and especially in the process of rewarming, the heartbeat recovered favorably as the pH returned closer to normal values. Cardiac resuscitation was usually easy, and no major arrhythmia was encountered. Fig4. Changes in base excess during anesthesia (measured at 38°C). (A)Average value in 52 patients. (B)Values in various cardiac conditions. (Abbreviations same as in Figure 2.)
Base excess was usually negative not only during rewarming but also thereafter, which may indicate that metabolic acidosis was present. Nevertheless, no special correction was required in most of the patients. Return to normal values was generally noted several hours after operation, with the patient who had the longest delay requiring a day for recovery (see Fig 4). Some variations were noted in serum electrolytes. The average preoperative value for sodium was 136 mEqlL; potassium, 4.3 mEq/L; and chlorine, 106 mEqlL. During the cooling process serum potassium decreased slightly in most patients, though occasionally it fell as low as 2.6 mEq/L just prior to the institution of cardiac anoxia. This trend, however, would reverse itself, and a gradual rise would begin during the process of rewarming so that at the completion of rewarming preoperative values were usually restored. Sodium and chlorine showed little change, even immediately before the cardiac standstill. After cooling was begun, electroencephalographic waves (from bipolar frontal leads) became gradually slower in proportion to the fall in body temperature, with a characteristic decrease of rapid waves as well as a decline in amplitude. Immediately before aortic occlusion and cardioplegia, the EEG was frequently observed to be flattened, and occasionally it completely disappeared. Excessively fast inhalation of ether caused rapid suppression of the EEG; the same trend was occasionally seen with a relatively VSD 17 VSDZPH 10 ASD 9 T/F 16
- 5 -
-
10 -
-
15
-
-20I
,
,
35 30' 25'
1
1
1
1
25' 30' 35'
1 1
Cooling Warming Circulatory Arrest 2 H r s A f t e r Surgery
1
,
35' 30'
I
,
I
25'
Cooling Warming Circulatory Arrest
,
336 The Annals of Thoracic Surgery Vol 22 No 4 October 1976
high body temperature. In this regard the EEG can serve as an index of the depth of anesthesia, the degree of cerebral hypoxia, and the state of the autonomic nervous system. As body temperature fell, prolonged P-Q and R-R intervals in the electrocardiogram indicated the onset of bradycardia. As long as anesthesia was adequate, sinus rhythm was usually maintained and would be until the time of circulatory occlusion. Supraventricular arrhythmia or atrial fibrillation might occasionally supervene, but in our experience these were always due to inadequate anesthesia, and sinus rhythm was usually restored with rapid inhalation of a small amount of ether. No remarkable changes were noted in the S-T segment and T wave. If bradycardia persists or restoration of sinus rhythm is delayed once resuscitation has begun, atrioventricular block should be considered. Right bundle-branch block can also appear after the incision has been made in the right ventricle. These abnormalities should be detected as early as possible and treated appropriately to ensure an uneventful postoperative course.
pulse rate parallel to a gradual fall in the body temperature can thus be ensured. If the anesthetic is given in insufficient quantities during the cooling process, peripheral vascular contraction is apt to occur, resulting in extensive shivering and thus imposing excessive stress on the patient that might preclude continuation of anesthesia. In order to prevent untoward occurrences during the cooling process, adequate titration of ether as well as the use of autonomic blocking agents with peripheral vasodilating action is of paramount importance. Excessively deep ether anesthesia, however, can cause peripheral circulatory insufficiency, suppression of cardiac function as manifested by an abnormal ECG, or profound hypotension. This makes subsequent cooling and resuscitation extremely difficult. It may also cause irreversible cerebral damage, and therefore one must be extremely cautious not to give an excessive amount of ether. Ether also has the property of concentrating blood. Hypothermia further exacerbates this effect, and complications such as sludging of the blood may occur. This, however, can be effecComment tively prevented by administration of lowEther anesthesia is widely used in profound molecular-weight dextran and heparin. Oxygen hypothermia despite its explosive properties consumption decreases markedly during and such disadvantages as its tendency to raise hypothermia, and cerebral damage, when it secretions in the airway. This is mainly because does occur, is believed to be due to the ether’s of the fact that it possesses a unique antiar- effect on both blood concentration and coagularhythmic effect. Ether can also inhibit cardiac bility rather than to tissue hypoxia secondary to function, however, and it is essential to keep the hypothermia and the operative procedure [l]. dose within a narrow therapeutic range in While many studies are available on the status which only the antiarrhythmic effect is ex- of acid-base balance during hypothermia, the pressed and no suppression of cardiac function results are not uniform. In our series base excess is exhibited. Since the body temperature of was often negative at the onset of anesthesia, human beings, who are homeothermic animals, which might have been partially due to the cannot be lowered below 20°C without the use of pharmacological action of ether, and it tended to anesthesia, an investigation of the potential in- decrease further with cooling, reaching as low as fluence of anesthesia upon the pathophysiology -10 mEqlL. Immediately after release of aortic of hypothermia is badly needed. At present, occlusion, however, a reversal of this condition however, neither the basic physiology nor the occurred and profound acidosis developed. It is biochemistry of hypothermia is clearly under- apparent that this was due to the outpouring stood, and this is why anesthesia under and subsequent circulation of acid substances hypothermia is accepted with much hesitancy. that had accumulated in the tissues because of In order to maintain desirable circulatory anaerobic metabolism during circulatory occluhemodynamics during hypothermic anesthesia, sion. This acidosis was transient, and the meit appears that skillful induction of the anes- tabolism stabilized quickly during rewarming. Nearly normal pH values were usually obthesia is most important. A gradual decline in arterial blood pressure and a smooth decrease of tained relatively early in the postoperative
337
Matsumoto et al: Profound Hypothermia Induced by Surface Cooling
period. Isayama [2] has pointed out that acidosis in hypothermia is not as important as it had been assumed to be and concluded that it may be connected with the nature of hypothermia per se. On the other hand, as pointed out by Mohri and co-workers [6], a more favorable anesthetic course is obtained if acidosis can be prevented before and after aortic occlusion. This is usually achieved by keeping Pat% low with induced hyperventilation and also by maintaining pH values at a rather high level, around 7.80, throughout the course. In any case, acid-base balance under hypothermia needs to be investigated further in light of the complex metabolic changes that take place. Many reports are available concerning electrolyte metabolism during hypothermia. In each, electrolyte concentration does not vary widely, and its relationship with hypothermia is not clearly established as yet [81. In our series sodium and chlorine showed few changes, and potassium was either at the lower limit of normal or slightly below it. The lowest value was encountered either at a body temperature of 24" to 25°C or at the time of circulatory occlusion. It is generally believed that changes in serum potassium level are directly related to the degree of fall in body temperature. However, the significance of this observation is as yet poorly understood. The electroencephalogram has long been used to evaluate the depth of anesthesia. Among anesthetic agents, ether has been studied most extensively for its effect on the EEG. As the anesthesia is deepened with ether, EEG amplitude i s usually increased, with a concomitant decrease in the cycle. Such a relationship is quite closely correlated, and EEG changes precisely reflect the concentration of ether in the arterial blood. In hypothermia with deep ether anesthesia the EEG does not disappear until the point immediately before aortic occlusion. Once ischemia is instituted, however, the EEG disappears within several seconds and reappears only when the body temperature rises above 30°C. There is a rapid recovery to normal after the temperature has reached 35°C. The electrocardiogram reflects cardiac status and depth of anesthesia. When anesthesia is too deep, myocardial suppression occurs, leading to hypotension; ECG abnormalities are usually
noted under such circumstances. The anesthesia should therefore be controlled within a very narrow range, and cooling should be started at the proper time; the ECG is an informative guide in determining this range. A favorable cardiac condition during the cooling process is characterized by a sustained, regular sinus rhythm with minimal S-T and T-wave changes. According to Okamura [71, ventricular fibrillation, along with other kinds of dysrhythmias, sometimes appears during hypothermia. In most cases this is due to an increase in myocardial irritability. In our experience, however, arrhythmias in hypothermia are usually manifested in the form of supraventricular rhythm disturbances, particularly atrial fibrillation or conduction abnormalities such as atrioventricular block. We have seen no instances of ventricular fibrillation.
References 1. Bjork VO, Holmdahl MH: The oxygen consumption in man under deep hypothermia and the safe period of circulatory arrest. J Thorac Cardiovasc Surg 42:392, 1961 2. Isayama T: Experimental studies on profound hypothermia from the viewpoint of acid-base balance in whole blood. J Jpn Surg SOC73:397, 1972 3. Ishikawa Y, Okamura H: Grenzen fur die Wieberbelebung bei Operation am offenen Herzen unter tiefer Hypothermia. Langenbecks Arch Chir 289:232, 1958 4. Matsumoto A, Nishi H, Sat0 S, et al: Studies of cerebral damage after open heart surgery using profound hypothermia with surface cooling: long-term follow-up studies. Yokohama Med J 23:111, 1972 5. Matsumoto A, Sat0 S, Kondo J, et al: Open heart surgery in neonates and infants using profound hypothermia with surface cooling. Cine seminar presented at the 22nd Annual Meeting of the American College of Cardiology, San Francisco, Feb 16, 1973 6. Mohri H, Dillard DH, Crawford EW, et al: Method of surface-induced deep hypothermia for open heart surgery in infants. J Thorac Cardiovasc Surg 58:262, 1969 7. Okamura H: Inhalation anesthesia for simple deep hypothermia induced by surface cooling. Med J Osaka Univ 20:29, 1969 8. Rittenhouse EA, Mohri H, Merendino KA:Studies of carbohydrate metabolism with prolonged circulatory occlusion. Surgery 67:995, 1970 9. Watanabe A: Experimental study of profound hypothermia induced with surface cooling. J Jpn Surg SOC 58:1675, 1958