Metabolic relevance during isolation technique in total arch repair for patients at high risk with embolic stroke

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1 doi: /icvts Interactive CardioVascular and Thoracic Surgery 7 (008) Institutional report - Vascular thoracic Metabolic relevance during isolation technique in total arch repair for patients at high risk with embolic stroke Takashi Kunihara*, Norihiko Shiiya, Kenji Matsuzaki, Yoshiro Matsui Department of Cardiovascular Surgery, Hokkaido University Hospital, Sapporo, Japan Received 31 July 007; received in revised form 10 October 007; accepted 11 October 007 Abstract In patients undergoing total arch replacement with protruding or mobile atheroma in the proximal aorta, we isolate cerebral circulation from systemic one by starting selective cerebral perfusion (SCP) before systemic arterial perfusion to prevent aortogenic embolic stroke. We disclose the safety of this isolation technique by measuring cerebral oxygenation and metabolism. Sixty-six patients underwent total arch replacement using SCP since The isolation technique was applied in sixteen patients. Jugular venous oxygen saturation (SjO ) was monitored in nine patients undergoing isolation technique (isolation-group) and in thirteen patients of the rest (conventional-group). Oxygen, glucose, and lactate extraction ratio (OER, GER, and LER) were measured at seven time points peri-operatively. The isolationgroup had significantly longer SCP time (isolation: 185"5 min vs. conventional: 140"43 min, P-0.01). During cooling, SjO was kept comparable between groups. OER was minimum at the end of cooling and comparable between groups (isolation: 3.8"7.7% vs. conventional: 11.7"13.8%, Ps0.37). There were no significant differences in GER and LER between groups. There were neither in-hospital death nor stroke. Temporary neurological dysfunction was observed only in conventional-group (ns3, 3%, Ps0.1). Isolation technique for total arch replacement could be performed safely and may provide acceptable results in patients at high risk for embolic stroke. 008 Published by European Association for Cardio-Thoracic Surgery. All rights reserved. Keywords: Total arch replacement; Isolation technique; Jugular venous oxygen saturation; Oxygen extraction ratio; Mobile atheroma; Embolic stroke 1. Introduction Based on increasing experimental and clinical evidences, trends of brain protection during total aortic arch replacement have changed over time. Currently, most experienced aortic surgeons seem to minimize hypothermic circulatory arrest (HCA) time and be in favor of antegrade continuous cerebral perfusion as an adjunct to protect the brain w1 5x. This mode of brain protection may decrease temporally neurological dysfunction, but embolic stroke cannot be satisfactorily prevented as one might expect. This may be because atheromatous emboli may be generated by manipulation of the diseased proximal aorta or by the arterial jet detaching protruding or mobile atheroma. Katz and colleagues reported that aortic arch atheroma is the only predictor of stroke during cardiac surgery w6x. Therefore, since 1998, we have applied a modified technique of selective cerebral perfusion (SCP) in patients undergoing total arch replacement with protruding or mobile atheromas in the proximal aorta. The modification is to isolate cerebral circulation from systemic one by starting SCP before systemic arterial perfusion. In 001, we reported favorable preliminary results of this isolation technique *Corresponding author. Department of Thoracic and Cardiovascular Surgery, University Hospital of Saarland, 6641 Homburg, Germany. Tel.: q ; fax: q address: chtkun@uniklinikum-saarland.de (T. Kunihara). 008 Published by European Association for Cardio-Thoracic Surgery applied in five patients w7x and have continued applying in a total of 16 patients thereafter. The drawback of this modification is that SCP must be initiated before systemic cooling. Therefore, it remains unclear whether this technique is really safe from the metabolic point of view. The purpose of this study is to clarify the safety of this isolation technique by measuring cerebral oxygenation and metabolism.. Materials and methods Sixty-six patients with aortic arch aneurysm underwent replacement of the entire aortic arch (with reconstruction of all three arch vessels) electively at Hokkaido University Hospital between June 1998 and November 005. Sixteen patients whose epiaortic echography findings of the proximal aorta were grade III or more, according to the report by Katz and colleagues w6x (grade III: sessile atheromas protruding -5 mm into the aortic lumen, grade IV: atheromas protruding G5 mm into the aortic lumen, grade V: protruding atheromas with mobile elements), were selected for receiving the isolation technique. Among them, nine patients who underwent isolation technique (isolationgroup) and thirteen patients from the rest (conventionalgroup) were measured for their cerebral oxygenation and metabolism throughout the operation and recruited in this study. We obtained approval from the institutional review

2 T. Kunihara et al. / Interactive CardioVascular and Thoracic Surgery 7 (008) board and written informed consent was given by all patients for measuring jugular venous oxygen saturation (SjO ) and collecting blood samples. Baseline variables were comparable between groups. The only difference between the two groups was epiaortic echography grading, which was greater in isolation-group than conventional-group (Table 1). All patients received preoperative evaluation of all neck vessels using a combination of Doppler echography and either computed tomographic angiography or magnetic resonance angiography, or both. Intracranial vessels were also evaluated in all patients. Then neither hemodynamic critical carotid stenosis nor intracranial lesion with indication for intervention was detected..1. Surgical techniques Our routine operative methods for total arch replacement were described previously in detail w8x. Briefly, when the bladder temperature reached 8C, SCP was initiated and the open distal aortic anastomosis was performed first under HCA of the lower torso, followed by systemic antegrade reperfusion through the side branch of a commercially available four-branched prosthesis. All three arch vessels were perfused routinely for SCP. Initial SCP flow was set around mlymin according to the patient s constitution, using two roller pumps independent from the systemic one. During systemic rewarming, proximal aortic anastomosis was performed. Finally, the arch vessels were connected to the side arms of the prosthesis. The detail of isolation technique was also described previously w7x. In the original technique, which was used in five patients of the present series, systemic perfusion was employed through the ascending aorta. In the remaining four cases, systemic perfusion was made through the axillary artery (right: 1, left:, both: 1). These modifications were used when atheromatous disease was present in the entire ascending aorta and there was no room for safe cannulation. The site of the axillar cannulation was carefully decided according to the preoperative neck vessels study and intraoperative epiaortic echography findings. A total of 19 arch vessels were directly cannulated through a sternotomy, while axillary artery cannulation was used in seven vessels. An 8-mm tube graft was attached to the axillary artery only in one. At first, only cerebral perfusion was initiated under normothermia and perfusate was cooled. When the nasopharyngeal temperature started to drop, neck vessels were isolated and systemic perfusion was started and systemic cooling began. The remaining part of the operation was not different from the conventional one. The only difference regarding SCP was that it was started before systemic cooling in isolation-group and at hypothermia (around 8C) in conventional-group... SjO monitoring and blood sampling Using a percutaneous retrograde approach, a 4 Fr oximetric catheter (OPTICATH, Abbott Laboratories, Abbott Park, IL) was placed in the right internal jugular venous bulb through a 5.5 Fr sheath. SjO was continuously monitored and recorded throughout the operation. We collected blood samples from both the radial artery and the internal jugular vein at the following seven times: just before and after the initiation of cardiopulmonary bypass (CPB) (T0, T1), just before HCA (T), one hour after the onset of SCP (T3), just after the conclusion of CPB (T4), just after skin closure (T5), and 1 h after surgery (T6). Oxygen contents, lactate and glucose levels in blood samples were measured immediately with a Radiometer ABL50 phyblood gas analyzer (Copenhagen, Denmark). Oxygen extraction ratio (OER), an index of cerebral metabolic function, was calculated according to the following equation: OER(%)s(CaO ycjo )ycao =100 (CaO : arterial oxygen content, CjO : jugular venous oxygen content) Lactate extraction ratio (LER) and glucose extraction ratio (GER) were also calculated in the same manner. Table 1 Baseline characteristics of the two groups Conventional ns13 Isolation ns9 P-value Gender (male) 10 (77%) 9 (100%) 0.1 Age (years) 74"6 7" Chronic aortic dissection 4 (31%) 0 (0%) 0.07 Previous aortic surgery 4 (31%) 1 (11%) 0.8 Previous pericardotomy 0 (0%) 0 (0%) NA Aneurysm size (cm) 61"9 6" Body weight (kg) 61"7 63" Body surface area (m ) 1.65" " Hypertension 11 (85%) 9 (100%) 0. Diabetes mellitus 0 (0%) 0 (0%) NA Peripheral artery disease 4 (31%) 1 (11%) 0.8 Carotid artery disease 0 (0%) 1 (11%) 0. Symptomatic cerebrovascular disease 1 (8%) 1 (11%) 0.78 Chronic obstructive pulmonary disease 1 (8%) (%) 0.33 Chronic renal failure 0 (0%) 0 (0%) NA Poor left ventricle function 1 (8%) 0 (0%) 0.39 EuroSCORE 9.7" " Epiaortic echography grading 1.4"0.9 3."

3 60 T. Kunihara et al. / Interactive CardioVascular and Thoracic Surgery 7 (008) Statistical analysis All values are expressed as mean"s.d. Statistical analysis was performed using StatView 5.0 (SAS Institute Inc., North Carolina, USA). Student s t-test was used for comparison of the continuous variables and the x -test was used for comparison of frequencies between the groups. A P-0.05 was considered statistically significant. 3. Results 3.1. Demographic data Fig. 1. Jugular venous oxygen saturation during cooling. There was no significant difference between groups with regard to duration of operation, CPB, aortic cross-clamping, and HCA. Only the duration of SCP was significantly longer in isolation-group than conventional-group (Table ). 3.. Metabolic data During core cooling, SjO was almost comparable between the two groups. In conventional-group, initial drop of SjO was seen as in normal CPB cases, which was not observed in isolation-group (Fig. 1). Mean OER was minimum at the end of cooling and that in isolation-group was not significantly different from that in conventional-group (3.8"7.7% vs. 11.7"13.8%, Ps0.37) (Fig. ). There were no significant differences in GER and LER between groups (Figs. 3, 4). Fig.. Cerebral oxygen extraction ratio during and after operation Clinical results There were neither in-hospital deaths nor stroke in this cohort. Temporary neurological dysfunction (TND) was observed only in conventional-group (three patients, 3%), but the difference did not reach statistical significance (Ps0.1). No significant difference was found between groups with regard to other postoperative morbidities. Fig. 3. Cerebral glucose extraction ratio during and after operation. Table Intraoperative demographic data Conventional ns13 Isolation ns9 P-value Concomitant operations 6 (46%) 1 (11%) 0.08 Coronary artery bypass grafting 5 (38%) 1 (11%) 0.16 Pulmonary vein isolation 1 (8%) 0 (0%) 0.39 Ascending aorta cannulation 11 (85%) 5 (56%) 0.13 Right axillary artery cannulation 1 (8%) 4 (44%) 0.04 Left axillary artery cannulation 3 (3%) 4 (44%) 0.9 Elephant trunk (15%) 0 (0%) 0. Stented elephant trunk 0 (0%) 3 (33%) 0.03 Selective cerebral perfusion flow (mlymin) 638"6 719" Selective cerebral perfusion flow (mlyminykg) 10.6" " Duration of operation (min) 459"08 478" Duration of cardiopulmonary bypass (min) 18"84 18" Duration of selective cerebral perfusion (min) 15"37 178"41 )0.01 Duration of aortic cross-clamping (min) 84"61 84" Duration of hypothermic circulatory arrest (min) 44"16 54" Minimum rectal temperature (8C) 19.7" " Minimum bladder temperature (8C) 19.4" " Intraoperative blood loss (l) 1.6" " Intraoperative red blood cell transfusion (l) 1.3" "

4 T. Kunihara et al. / Interactive CardioVascular and Thoracic Surgery 7 (008) Fig. 4. Cerebral lactate extraction ratio during and after operation. 4. Discussion Although we already became confident with the clinical safety and efficacy of our isolation technique to prevent embolic stroke in high-risk patients in 001 w7x, pathophysiology of the brain during this unphysiological condition remains unclear. Because SCP is established at higher temperature than usual, energy supply demand imbalance may be present, which may lead to subclinical neurological deficit such as neurocognitive decline. However, the current results showed that cerebral oxygenation and metabolism during and after isolation technique seemed comparable with conventional technique. Furthermore, the clinical results in the isolation-group were at least comparable with those in the conventional-group, despite the fact that the former was used for the high-risk patients for embolic stroke. Although SCP can prolong the safe duration of arch vessel reconstruction, it may not completely prevent embolic stroke. Transcranial Doppler monitoring indicates that microemboli occur commonly during CPB maneuvers. When protruding or mobile atheroma exists in the proximal aorta, the risk of generating emboli will exponentially increase. Katz and colleagues reported that the risk of stroke after cardiac surgery was 5% in patients with mobile atheroma, whereas it was only 1.7% in the others w6x. Therefore, we have refined our SCP technique to isolate all the three arch vessels from the systemic one before starting systemic perfusion. We believe that isolation of the left vertebral artery from embolic load is important, because it has been documented that intraoperative strokes affect the posterior part of the hemispheres and cerebellum in a majority of patients w9x, and because the left vertebral artery is predominant in the majority of cases. Then we believe that we could effectively reduce embolic stroke in our high-risk patients. Although conceptually promising, our isolation technique had lacked the support of metabolic data to confirm its safety. In the current study, SjO data during cooling suggest that isolation technique could cool the brain similar to conventional one. Minor modification of isolation technique that uses the right axillary artery for systemic perfusion might also perfuse the right common carotid artery more sufficiently than the others. Furthermore, OER at the end of cooling of isolation-group was not higher than that of conventional-group. This also means oxygen supplyydemand mismatch in the brain did not occur in both groups. The level of brain lactate is assumed to be a marker of inadequate balance of oxygen supply and demand in the brain w10, 11x. Under pathological conditions (stroke, head injury, hypoxia, ischemia, and so on), the brain can use lactate as a metabolic substrate, whereas metabolic rate of glucose, a primary energy source, is decreased w1x. Since blood brain barrier is permeable to lactate as well as glucose, it seems worth measuring arterio-jugular venous (A-J) differences of glucose and lactate to estimate flowmetabolism uncoupling in the brain. Under aerobic conditions, the brain is a lactate-producing organ. Therefore, it has been reported that A-J difference of lactate is nearly zero, or a bit minus, under physiological condition in a human w13, 14x or rat w1, 15x. Unaerobic condition is associated with increased A-J difference of lactate. In the current study, preoperative LER of both groups are consistent with other reports. Throughout the measurements, LER of both groups seems parallel, which suggests that isolation technique would provide near-physiological condition to the brain as well as conventional SCP. However, LER tended to increase after HCA. It has been reported that elevated blood lactate level is accompanied with increased lactate uptake into the brain w1x. Furthermore, it has been observed that hyperglycemia increases cerebral lactate level w10x. Therefore, increased blood levels of both lactate and glucose after HCA might potentiate increase of LER in this period in our patients Study limitations Some limitations are inherent to the current study. Mainly, the detail of our isolation technique was not uniform. There were several alternatives in the cannulation site for systemic perfusion. SCP flow was also not equivalent between patients. Nevertheless, our results that isolation technique was associated with neither an increased operative risk nor metabolic disadvantage might justify our modification of SCP to prevent embolic stroke in high-risk patients. 5. Conclusion Despite some limitations, results of the present study on the brain metabolism during selective cerebral perfusion suggest that isolation technique for total arch replacement could be performed safely. In this small cohort but with high-risk profile for embolic stroke, clinical results seem acceptable. Our indication of isolation technique thus seems justified. References w1x Bachet J, Guilmet D, Goudot B, Dreyfus GD, Delentdecker P, Brodaty D, Dubois C. Antegrade cerebral perfusion with cold blood: a 13-year experience. Ann Thorac Surg 1999;67: wx Kazui T, Yamashita K, Washiyama N, Terada H, Bashar AH, Suzuki T, Ohkura T. Usefulness of antegrade selective cerebral perfusion during aortic arch operations. 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