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Ann Thorac Surg 1998;66:1179-1184
© 1998 The Society of Thoracic Surgeons

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Original articles: cardiovascular

Circulatory arrest under moderate systemic hypothermia and cold retrograde cerebral perfusion

^a Division of Cardiovascular Surgery, The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada

Address reprint requests to Dr David, 200 Elizabeth St, 13EN219, Toronto, Ont, Canada M5G 2C4
e-mail: (aats{at}torhosp.toronto.on.ca)

Presented at the Thirty-fourth Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 26–28, 1998.

	Abstract

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Background. Profound hypothermia is used for circulatory arrest during cardiovascular operations. Cold retrograde cerebral perfusion enhances cerebral protection during circulatory arrest. This study examines the results of circulatory arrest under moderate systemic hypothermia and cold retrograde cerebral perfusion.

Methods. Circulatory arrest under moderate systemic hypothermia (nasopharyngeal temperatures of 19° to 28°C, mean of 23°C) and cold (10°C) retrograde cerebral perfusion were employed in 104 consecutive patients for operation on the proximal aorta (103 patients) or for a venous tumor invading the heart (1 patient). Aortic operations consisted of replacement of the entire transverse arch in 49 patients, hemiarch in 16, ascending aorta in 37, and an extraanatomic aortic bypass in 1. Most patients (83%) also had other procedures such as coronary artery bypass or an aortic valve operation. Sixteen patients had had previous aortic operations. The mean circulatory arrest time was 27 minutes (range, 6 to 105 minutes).

Results. There were eight in-hospital deaths. Preoperative shock, peripheral vascular disease, and previous aortic operations were independent predictors of operative mortality. There were eight strokes; clinical assessment and computed tomographic scans of the brain suggested that the strokes were embolic in 6 patients. Atherosclerosis/laminated thrombi in the aorta and the duration of circulatory arrest were independent predictors of stroke. Four patients had seizures without neurologic deficit. No patient had development of paraplegia or paraparesis.

Conclusions. Systemic hypothermia of 23°C (nasopharyngeal) and cold retrograde cerebral perfusion (10°C) appear to be safe for circulatory arrest times of less than 30 minutes. This strategy of cerebral protection may also be adequate for longer circulatory arrest times.

	Introduction

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Hypothermic circulatory arrest (HCA) is a well established method of cerebral protection during cardiovascular operations [1, 2]. The systemic temperature is usually lowered to less than 18°C and maintained low for several minutes before cardiopulmonary bypass can be safely stopped [2]. This technique provides good cerebral protection and a dry operative field but it requires prolonged cardiopulmonary bypass to cool and to rewarm the patient, and it is often associated with coagulopathy [3, 4]. Cold retrograde cerebral perfusion (RCP) has been proposed as an adjunct to HCA to enhance cerebral protection [5, 6]. Although it is not entirely understood how RCP protects the brain, one of its features is that it maintains the central nervous system cool.

Since we began to employ RCP during HCA in 1990, we observed that the nasopharyngeal temperature at the end of the HCA was frequently lower than at the beginning of the HCA. Because it was possible to cool the central nervous system with cold RCP, we started to discontinue cardiopulmonary bypass before the systemic temperature reached 20°C in cases in which we expected a short period of HCA. During the past 5 years we have used exclusively moderate systemic hypothermia whenever RCP was used during HCA. We lowered the systemic temperature to 22° to 28°C depending on the anticipated duration of HCA and used RCP at 10°C. In this report we describe our current experience with this strategy during HCA.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
From January 1992 to October 1997, 104 consecutive patients underwent cardiovascular operations by two surgeons using moderate HCA and cold RCP at The Toronto Hospital. Table 1 shows the patients’ profile.

Operative management
Anesthesia was induced and maintained as per our early extubation protocol [7]. Tranexamic acid (50 to 100 mg/kg) was given intravenously to all patients. No corticosteroids or barbiturates were given during the operation. The patient’s head was not packed in ice bags because we believe that RCP is an effective method to cool the entire head.

Nasopharyngeal temperature was monitored in all patients and rectal temperature in 37. For this reason, all remarks and analysis made in this study are based on nasopharyngeal temperature. It is noteworthy to mention that in the 37 patients who had both temperatures recorded, the rectal temperature was always higher than the nasopharyngeal by a mean of 6° ± 3°C (mean ± standard deviation).

Median sternotomy was used in all patients. A standard cardiopulmonary bypass circuit with a crystalloid priming solution was employed. The arterial cannula was inserted in the distal ascending aorta or transverse arch in 78 patients, into the femoral artery in 24, and in both the arch and femoral artery in 2. After the HCA, antegrade arterial perfusion was used in all patients. The right atrium was cannulated for venous drainage.

Circulatory arrest was initiated when the systemic temperature reached 22° to 28°C, depending on the complexity of the case. The nasopharyngeal temperature decreased in most cases during RCP. The lowest temperature attained was recorded. The lowest mean and median temperatures were 23°C and 24°C, respectively (range, 19° to 28°C). Retrograde cerebral perfusion was delivered through a small cannula inserted into the superior vena cava. During RCP the cava was snared between the right atrium and azygos vein. The temperature of the perfusate was lowered to 10°C during RCP. Most of the perfusate was sequestrated in a reservoir and less than one half of its volume was exposed to low temperatures during the HCA. Central venous pressure was maintained at around 25 mm Hg during RCP. The mean flow rate was approximately 400 mL/min (range, 250 to 500 mL/min). The mean and median HCA times were 27 and 24 minutes, respectively (range, 6 to 105 minutes). In patients who had replacement of the entire arch the mean and median HCA times were 35 and 32 minutes, respectively (range, 18 to 105 minutes), and the mean and median temperatures were 22° and 22°C (range, 19° to 26°C).

Antegrade, retrograde, or antegrade and retrograde cold blood cardioplegia were used for myocardial protection. The mean and median aortic cross-clamp times were 93 and 92 minutes, respectively (range, 20 to 197 minutes). The mean and median cardiopulmonary bypass times were 138 and 135 minutes, respectively (range, 68 to 344 minutes). The mean duration of the operation was 222 ± 69 minutes (range, 130 to 470 minutes).

Statistical analysis
Categoric data were analyzed by a ² test. Continuous data were analyzed by two-tailed t test. Variables were selected for inclusion in a multivariable model if their univariate p value was less than 0.05 or if the variable was of known clinical importance. Stepwise logistic regression was performed for operative mortality, stroke, and coagulopathy by the BMDP LR program (BMDP Statistical Software Inc, Los Angeles, CA). Odds ratios with 95% confidence interval are presented for independent predictors of outcome. Odds ratios for continuous variables are scaled to a one-unit change in the variable. To determine correlation between circulatory arrest time and cooling temperature, multiple linear regression for independent predictors of nasopharyngeal temperatures was performed.

	Results

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
There was a linear correlation between duration of HCA and the level of hypothermia; the longer the arrest, the lower the temperature (r = 0.46; p = 0.0001). Patients who had HCA of 30 minutes or greater had systemic temperatures of 19° to 24°C.

There were eight in-hospital deaths (7.7%). The causes of deaths were low cardiac output in 4 patients, stroke in 2, low cardiac output and stroke in 1, and ischemic bowel in 1. With the exception of a patient who died of perioperative myocardial infarction and coagulopathy after repair of acute type A dissection, all other deaths occurred among patients who either were moribund before the operation or required very complex reoperative procedures. Univariate analysis revealed that preoperative shock (43% versus 5%; p = 0.001), peripheral vascular disease (31% versus 4%; p = 0.001), urgent/emergent operation (16% versus 1.7%; p = 0.006), rupture of transverse arch (29% versus 6%; p = 0.03), aortic dissection (18% versus 4%; p = 0.03), and severe chronic obstructive pulmonary disease (29% versus 6%; p = 0.03) were significant predictors of mortality. Previous aortic operation was of borderline significance (19% versus 6%; p = 0.07). A stepwise logistic regression analysis showed that preoperative shock, peripheral vascular disease, and a previous aortic operation were independent predictors of operative mortality. However, the extremely wide confidence intervals that emerged in this model render the odds ratios of these risk factors meaningless.

There were eight strokes (7.7%). Three patients failed to wake up from anesthesia, remained in a coma, and died in the hospital. A 69-year-old man presented in shock and was unconscious before operation because of a ruptured transverse arch. He had an atherosclerotic arch aneurysm, peripheral vascular disease, and severe chronic obstructive pulmonary disease. He remained in a low cardiac output state, required renal dialysis, and never regained consciousness in spite of a normal computed tomographic scan of the head (HCA = 50 minutes; temperature = 20°C). The second patient was a 72-year-old woman with unstable angina who had reoperative coronary artery bypass and replacement of a severely atherosclerotic ascending aorta and transverse arch. She failed to wake up; a computed tomographic scan of the brain showed multiple infarcts (HCA = 33 minutes at 19°C). The third patient was a 62-year-old woman with atherosclerotic aneurysm of the entire thoracic aorta with laminated thrombi in the arch and descending thoracic aorta. She had replacement of the transverse arch using the elephant trunk technique. She failed to wake up; a computed tomographic scan showed massive right parietal and bilateral cerebellar infarctions (HCA = 30 minutes at 22°C). The stroke in the remaining 5 patients was caused by malperfusion of the innominate artery in the setting of acute type A aortic dissection in 1 and embolism in 4 as assessed clinically and by computed tomographic scans of the brain. Of these 5 patients, 3 recovered completely and 2 had a permanent neurologic deficit. All but one stroke occurred among 33 patients who had either atherosclerotic aorta, calcified arch aneurysms, or aneurysms with laminated thrombi. Univariate analysis revealed that atherosclerosis/laminated thrombi in the ascending aorta or arch (21% versus 4%; p = 0.005), peripheral vascular disease (23% versus 5%; p = 0.018), ruptured aortic arch (29% versus 6%; p = 0.03), and total arch replacement (14% versus 1.8%; p = 0.046) were predictors of stroke. The duration of HCA was of borderline significance (45 versus 25 minutes; p = 0.07). A stepwise logistic regression analysis showed that atherosclerosis/laminated thrombi in the aorta (odds ratio, 7.4; 95% confidence interval, 1.3 to 41.6) and HCA duration (odds ratio, 1.07/minute; 95% confidence interval, 1.02 to 1.12) were the only two independent predictors of stroke.

Four patients suffered seizures without neurologic deficit during the first postoperative day. Thus, a total of 12 patients (11.5%) experienced neurologic complications. Table 3 shows the incidence of neurologic complications and deaths stratified to HCA time intervals. All neurologic events but one occurred in patients who had HCA of 30 minutes or longer. There were no other neurologic complications. No patient had evidence of paraplegia/paraparesis or any other peripheral nerve dysfunction.

Five patients (4.8%) required renal dialysis, and 3 of them died. Four of these patients were moribund before the operation; 2 of these 4 patients had chronic renal failure preoperatively.

	Comment

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
This study suggests that it may not be necessary to cool the whole body to temperatures less than 20°C during HCA when continuous cold RCP is used. The in-hospital mortality rate of 7.7% observed in this study compares with those in contemporary series of HCA with RCP that report in-hospital mortality of 3.4% to 19.7% [8–12]. As in other studies, death was primarily related to the preoperative status of the patients [8–11]. In our series, low cardiac output state was a major cause of death, and all patients who died were either in shock preoperatively or underwent complex and long reoperative procedures. Hence, preoperative shock, peripheral vascular disease, and a previous aortic operation were independent predictors of in-hospital mortality. Neither univariate nor multivariate analysis showed circulatory arrest time to be a predictor of death. Obviously, this may be related to the fact that only 3 patients had circulatory arrest time greater than 60 minutes.

The overall stroke rate in this study was 7.7%, and it is similar to that of previous reports on deep HCA alone or combined with RCP [9, 11, 13–15]. In our study atherosclerosis or laminated thrombi in the aorta and the duration of HCA were found to be independent predictors of stroke. Clinical assessments and computed tomographic scans of the brain suggested that the strokes were embolic in 6 of 8 patients. We have always avoided retrograde femoral perfusion in patients with atherosclerosis of the aorta or aneurysms with laminated thrombi. However, it is possible that the embolic strokes occurred during cannulation of the ascending aorta/arch or during cardiopulmonary bypass before HCA.

There was a marked increase in the incidence of stroke in patients who had HCA of 30 minutes or longer (see Table 3). Indeed, in addition to bad aorta, the duration of HCA was identified as an independent predictor of stroke. This finding caused us to be concerned about the safety of circulatory arrest under moderate hypothermia and cold RCP. However, careful review of every patient indicated that other factors such as diseased aorta, preoperative shock, previous aortic operation, and ruptured transverse arch played a role in the development of the neurologic complication. In addition, patients who suffered stroke had the lowest temperatures in the series because the anticipated operations were complex and would require a longer HCA. Clinical and animal studies by other investigators showed that RCP provides between 10% and 30% of baseline cerebral blood flow when administered at jugular pressures of 20 to 25 mm Hg, and may extend the safe period of deep HCA up to 90 minutes [15]. Lin and associates [16] reported the safety of circulatory arrest under moderate systemic hypothermia and cold RCP in 23 patients with Marfan’s syndrome and aortic dissection who required circulatory arrest times of a mean of 75 minutes (range, 58 to 104 minutes) without any stroke. These studies support our clinical impression that moderate HCA with cold RCP is a safe technique for circulatory arrest times even greater than 30 minutes. The fact no paraplegia or paraparesis developed in any of our patients attests to the efficacy of this method in also protecting the spinal cord.

The advantage of this technique is the shortened cardiopulmonary bypass time, which in turn may decrease the risk of neurologic dysfunction as well as of coagulopathy. During cardiopulmonary bypass the microcirculation is bombarded with microemboli that may cause neuropsychological deficit, the risk of which is proportional to the duration of the bypass [17]. Interestingly, bypass time was an independent predictor of stroke in a large series of HCA with RCP [18]. In addition, prolonged bypass increases the risk of coagulopathy [19]. In our series, the mean cardiopulmonary bypass time for patients who sustained coagulopathy was 171 minutes compared with 128 minutes for patients who did not (p = 0.0012). Bypass time also emerged as an independent predictor of coagulopathy (odds ratio, 1.02/minute). Although the effect of deep hypothermia on hemostasis is not well known, it may increase the hemostatic defect by severely affecting platelet function [3]. To avoid that during cold RCP, only part of the perfusate was cooled to 10°C in our patients.

In conclusion, this study showed that circulatory arrest under moderate systemic hypothermia and cold RCP provides good cerebral protection for up to 30 minutes. The size of our study population is too small to draw conclusions regarding the safety of this technique for circulatory arrest of longer duration.

	Acknowledgments

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
The statistical analysis in this study was performed by Joan Ivanov, MSc. We are indebted to her.

	References

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 

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