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J Thorac Cardiovasc Surg 2007;133:501-509
© 2007 The American Association for Thoracic Surgery
Cardiopulmonary Support and Physiology |
Division of Thoracic and Cardiovascular Surgery, Hannover Medical School, Hannover, Germany
Received for publication February 14, 2006; revisions received July 20, 2006; accepted for publication September 5, 2006. * Address for reprints: Hiroyuki Kamiya, MD, Department of Cardiac Surgery, University of Heidelberg, INF 110, 69120 Heidelberg, Germany (Email: Hiroyuki.Kamiya{at}med.uni-heidelberg.de).
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Abstract |
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METHODS: Between October 1999 and August 2005, a total of 377 patients underwent repair of the aortic arch with selective cerebral perfusion and hypothermic circulatory arrest at 20°C to 28°C and were divided into two groups: (1) 125 patients with deep lower body circulatory arrest at 20°C to 24.9°C (deep lower body circulatory arrest group) and (2) 252 patients with moderate lower body circulatory arrest at 25°C to 28°C (moderate lower body circulatory arrest group). To compensate for the differences in patient characteristics, we used a propensity score matching analysis, and comparable patients, 92 patients from each group, were identified for final analysis.
RESULTS: There were no significant differences in mortality or morbidity between deep and moderate lower body circulatory arrest, in either the entire study cohort or the propensity-matched cohort. C-reactive protein level 1 day after the operation approached but fell short of significance (108.4 ± 47.7 mg/L in deep lower body circulatory arrest group and 95.8 ± 44.2 mg/L in moderate lower body circulatory arrest group, P = .07). The mean temperatures at the initiation of lower body circulatory arrest were 24.1°C ± 2.2°C in patients who underwent reexploration for bleeding and 24.9°C ± 1.8°C in patients who did not (P = .025); the difference also reached statistical significance in multivariate analysis (P = .046, odds ratio 0.796).
CONCLUSIONS: Our results suggest that moderate lower body circulatory arrest can be safely performed for aortic arch repair. In fact, postoperative inflammatory response tended to be lower in patients with moderate lower body circulatory arrest than those with deep lower body circulatory arrest, and deep lower body circulatory arrest was a strong risk factor for reexploration for bleeding.
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Introduction |
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TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
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these complex procedures are still associated with a relatively high mortality and high incidences of neurologic complications. As is well known, the safe duration of HCA alone is limited,3-6 and HCA is therefore normally performed with the use of retrograde cerebral perfusion or antegrade selective cerebral perfusion (SCP). Because the real benefit of retrograde cerebral perfusion is not uniformly accepted,6,7 the combination of HCA and SCP is currently adopted in many institutions. There is no common guideline as to the temperature that should be achieved before extracorporeal circulation can be stopped and followed by the initiation of SCP, however, and each institution has its own protocol. Until now, discussions regarding HCA have been focused on cerebral protection and neurologic outcome. Originally, deep HCA was introduced as a method of cerebral protection, and because the brain is the most sensitive organ to ischemic injury, it is considered that the temperature should be dropped to 20°C or lower when no other adjunct cerebral protection is available. With the use of SCP, however, HCA acts as lower body circulatory arrest (LBCA), and the temperature for HCA can therefore be higher. To distinguish between HCA of the entire body and HCA of the lower body, HCA with the use of SCP is defined as LBCA in this article.
In recent years, the trend has gone from deep temperatures, cooler than 20°C as advocated by the Mount Sinai group,6 toward temperatures as high as 25°C.8-10 The avoidance of deep core temperatures at LBCA may offer the advantage of shorter cardiopulmonary bypass (CPB) times and reductions in coagulation disorders and the accumulation of inflammatory parameters, but it can theoretically cause ischemic injury to the visceral organs and the spinal cord.
In our institution, SCP was introduced in 1999 in combination with deep HCA at temperatures lower than 20°C. The temperature of LBCA has gone higher as we gained experience, and it is now performed at 25°C to 28°C. This temperature is clearly higher than in other institutions, where it is performed at 20° to 25°C.8-10 It is difficult to say whether the results are acceptable, however, because previous studies had no control group regarding the temperature of LBCA. The aim of this study was to compare the in-hospital outcomes of patients with LBCA at 25°C to 28°C with those of a propensity-matched group of patients with LBCA at 20°C to 24.9°C.
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Patients and Methods |
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and a venous single two-stage cannula in the right atrium. The left side of the heart was vented through the right superior pulmonary vein. Myocardial protection was achieved with cold blood cardioplegia. The ascending aorta was clamped, and manipulation of the proximal site was performed. After the patient was cooled to the target temperature, the systemic circulation was arrested, the aneurysm was opened, and the arterial cannula was removed. With the patient in the Trendelenburg position, 15F retrograde coronary sinus perfusion cannulas (Medtronic DLP, Grand Rapids, Mich) connected to the oxygenator with a separate single-roller pump head were inserted into the innominate artery and the left carotid artery. The left subclavian artery was clamped or occluded with a Fogarty catheter (Baxter Healthcare Corporation, Deerfield, Ill) to avoid the steal phenomenon. For SCP, cold blood at 15°C was perfused with a circuit for blood cardioplegia. Cerebral perfusion was initiated at a rate of 10 ml/(min · kg) and adjusted to maintain a pressure between 40 and 60 mm Hg. After the aortic arch was repaired, SCP was ceased and CPB was resumed with the perfusion cannula directly reinserted into the graft. Deairing was performed in a standard manner.
Definitions of Complications
In accordance with the report by Ergin and colleagues,5 we defined temporary neurologic dysfunction as the occurrence of at least one of the following symptoms: postoperative confusion, agitation, delirium, prolonged obtundation, or transient parkinsonism without obvious neurologic deficit. Stroke was defined as the presence of transient or permanent focal neurologic deficit that was confirmed as a new deficit by means of computed tomography. Respiratory insufficiency was defined as prolonged intubation for more than 48 hours because of inadequate status of gas exchange. Criteria for extubation included adequate response to commands, respiratory rate greater than 12 breaths/min, end-tidal carbon dioxide tension less than 50 mm Hg, and an oxygen saturation by pulse oximetry greater than 95% at an inspired oxygen fraction of 0.3.
Statistical Analysis
Results are expressed as mean ± SD. Statistical analyses were performed with the Student t-test for continuous variables or with 
2 tests (Fisher exact tests if n < 5) for categorical variables.
In view of the marked and significant differences in patient characteristics between the groups, patient matching seemed necessary to evaluate the genuine effects of temperature on mortality and morbidity. To compensate for the differences in this retrospective, nonrandomized study, we used a propensity score matching analysis. For this purpose, logistic regression was used to develop a propensity score.11,12 The propensity score included age, sex, body mass index, reoperation, emergency operation, Marfan syndrome, previous neurologic events, smoking history, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, diabetes mellitus (insulin dependent), peripheral vascular disease, coronary artery disease, renal insufficiency (creatinine >2.0 mg/dL), total arch replacement, concomitant operations (aortic valve root operation, coronary artery bypass grafting, mitral valve operation), duration of aortic crossclamping, and duration of LBCA. From these covariables, a propensity score was calculated for each patient. Finally, each patient in the deep LBCA group was matched with a patient in the moderate LBCA group with the closest propensity score. The maximum difference in propensity score for a match was less than 0.015. By using this novel method, comparable patient groups (92 patients from each group) were identified for final analysis (Table 1). Logistic regression was also used for the analysis of risk factors for postoperative mortality and morbidity and the effects of temperature on postoperative mortality and morbidity. All statistical analyses were performed with SPSS 10.0 software (SPSS Inc, Chicago, Ill).
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Results |
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TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
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Time courses of the following factors were also analyzed in the propensity-matched groups: blood urea nitrogen, creatinine, and urinary output as an index of renal function; aspartate aminotransferase as an index of liver injury; creatine kinase as an index of muscle injury; lactate as an index of whole-body ischemic injury; C-reactive protein as an index of inflammatory response; and ratio of arterial to inspired oxygen concentration as an index of gas exchange function (Appendix Table E1). Only the difference in C-reactive protein level at 1 day after the operation approached (but did not reach) statistical significance (108.4 ± 47.7 mg/L in deep LBCA group vs 95.8 ± 44.2 mg/L in moderate LBCA group, P = .07; Figure 2).
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Discussion |
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TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
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At the beginning of this study, we found the differences in the distribution of patient baseline data to be too great for a proper analysis. Patients with deep LBCA had lower body mass index, greater incidence of Marfan syndrome, and more smoking history. Moreover, they underwent fewer concomitant procedures (Appendix Table E2), more total arch replacement, and longer duration of LBCA. To generate a reasonable control group, propensity matching was performed for this study.12,13 Because LBCA and aortic crossclamping times are dependent on the surgical procedure and independent of the temperature at the initiation of LBCA, both factors were included in the matching process. Operative and CPB times were not included in this process, because we considered those factors to be dependent on LBCA, aortic crossclamping, cooling, rewarming, and hemostasis times.
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and Harrington and associates14 reported that mean CPB times were 191 ± 53 minutes in a deep hypothermic CPB group and 131 ± 48 minutes in a moderate hypothermic CPB group (P < .0001), with their deep hypothermic CPB group undergoing HCA for 31 ± 14 minutes. Theoretically, longer cooling and rewarming times are required for deep HCA; in our series, however, 75% of patients underwent concomitant procedures during the cooling and rewarming phases. This may account for the lack of differences in CPB and operative times between the two groups. As we speculated, there were no differences in neurologic adverse event between the groups in any analysis. SCP protocol was identical in the two groups, and hypothermia was only needed as a brain protection during the period from the termination of CPB to the initiation of SCP and from the termination of SCP to the resumption of CPB. In our series, the difference between HCA and SCP times was approximately 6 minutes. Our data suggest that the difference in temperature at LBCA does not affect the quality of cerebral protection during this period.
Although the spinal cord consists of neural cells such as are present in the cerebrum and is most likely sensitive to ischemic damage in a similar manner as in the brain, the occurrences of paraplegia were similar in the two groups. This outcome may have been due to our institutional perfusion protocol. We performed SCP with cold blood at 15°C, and it was observed in general that the nasopharyngeal temperature would continue to fall during the LBCA period, commonly dropping to 20°C, although the temperature of the bladder would remain at the temperature at the initiation of LBCA. The mechanism of this phenomenon is unclear, but perhaps it was caused by the collateral blood flow through the vertebral artery and the returned cool blood from the head to the right atrium. It can be speculated that this cooling phenomenon acted protectively for the spinal cord and therefore resulted in a relatively low incidence of paraplegia among patients with moderate LBCA.
There were also no differences in the biologic parameters of any other organs. Similar to our results, Harrington and associates14 concluded that hypothermic CPB is not a risk factor for renal or early pulmonary dysfunction. Generally, visceral organs, including the lungs, can tolerate ischemic damage better than can the brain or the heart. Our results suggest that visceral organs can be well protected by moderate LBCA.
In this series, only the difference in C-reactive protein level 1 day after the operation approached statistical significance (P = .08). The actual adverse effects of deep hypothermia on inflammatory response have not been made clear, but our results suggest that deep LBCA may activate inflammatory response, as others have already speculated.7,15 This issue, however, appears to be difficult to prove in a clinical setting. In this series there were no differences in any clinical outcomes except reexploration for bleeding.
It is well known that coagulopathy is induced by hypothermia16,17 but it has been difficult to prove this association in a clinical setting, especially with regard to HCA, as seen in the report by Harrington and associates14 in which profound hypothermia was not associated with increased postoperative hemorrhage in their comparative study of deep HCA.14 In our study, reexploration for bleeding was the only factor significantly associated with temperature. This result suggests that the use of deep LBCA can possibly cause postoperative bleeding.
Generally, acute aortic dissection type A is associated with high mortality, and this was also the case in our series. Even in this high-risk cohort, however, there were no differences in clinical outcome between the two groups. Our results demonstrate that moderate LBCA is a safe strategy for the treatment of acute aortic dissection type A.
Among the patients who underwent HCA for longer than 60 minutes, 2 patients (1 with acute aortic dissection type A and 1 without it) who underwent moderate LBCA had paraplegia occur, whereas none of those who underwent deep LBCA did (P = .08). There were neither significant differences nor any trends toward significance in any other postoperative adverse effects. In our entire study cohort, only 7% of the patients (n = 27) underwent LBCA for longer than 60 minutes, as shown in Figure 1, and this patient volume was too small to conclude anything from a subanalysis. On the other hand, LBCA time was 50.2 ± 20.7 minutes among patients who underwent total arch replacement and 20.4 ± 13.1 minutes among patients who underwent hemiarch replacement (P = .0001), and the percentages of paraplegia were 4.7% (4/85 patients) and 1.4% (4/292 patients), respectively (P = .064). In our institution, arch vessels are commonly reconstructed as an island, and this might explain why most of the cases were completed with less than 60 minutes of LBCA. Here it should be strongly emphasized that the results of this study do not support the suggestion that moderate LBCA has no time limit, and this method should not be used for patients who require complex total arch replacement with individual arch vessel reconstruction.
Unfortunately, we could not find the optimal temperature for LBCA and consider this a study limitation. The LBCA temperature ranged mainly from 25°C to 28°C, and the optimal temperature could not be identified with this concentration in distribution in our preliminary pilot study. The temperature of 25°C to 28°C is quite higher than reported in other institutions,8-10 however, and we believe that it is meaningful to analyze and discuss the safety of LBCA in this temperature range.
In conclusion, there were no significant differences in mortality or morbidity between deep and moderate LBCA in either the entire study cohort or the propensity-matched cohort. There was a trend toward lower postoperative inflammatory response in patients with moderate LBCA, however, and deep LBCA was strongly associated with reexploration for bleeding. Our results suggest that moderate LBCA can be safely performed for aortic arch repair for 60 minutes or less. It remains unclear whether it is safe beyond 60 minutes.
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H. Kamiya, K. Kallenbach, A. Haverich, and M. Karck Reply to the Editor J. Thorac. Cardiovasc. Surg., March 1, 2008; 135(3): 714 - 714. [Full Text] [PDF]
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H. Kamiya, K. Kallenbach, A. Haverich, and M. Karck Reply to the Editor J. Thorac. Cardiovasc. Surg., March 1, 2008; 135(3): 715 - 716. [Full Text] [PDF]
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