2. Akiko Inoue, DO 2/17/2010

3.  The perioperative risk of stroke for patients undergoing carotid endarterectomy (CEA).  Literature has not provide consistent measures to reduce this risk.  Reversal of neurological deficit due to cerebral hypoperfusion after carotid artery cross-clamping has been demonstrated by increasing inspired oxygen fraction (FIO 2 )  Regional oxygenation (rSO 2 ) has been shown to improve by increasing FIO 2.

4.  In healthy subjects, both middle cerebral flow velocity and rSO 2 increase with increase in PaCO 2.  Studies have shown paradoxical improvements in cerebral blood flow on the ipsilateral side of cross-clamping with hypocapnia. Hypocapnia restores cerebral autoregulation during isoflurane anesthesia.  Cerebral near-infrared spectroscopy (NIRS) monitors continuous rSO 2 and estimates balance between cerebral O 2 supply and demand.

5.  Hypothesis: ◦ To determine whether increases in the FIO 2 or PETCO 2 correlate to a significant change in rSO 2 in patient undergoing CEA under general anesthesia with and without shunts during the period of the carotid cross- clamp.  Methods: ◦ Prospective, controlled (pilot study, each pt acted as their own control) study ◦ 20 subjects (10 shunting, 10 w/o shunting) recruited, partial data from 1 subject of unshunted group were excluded 2/2 hypotension. ◦ Exclusion criteria  Refused to consent, respiratory failure, or non-English speaker.

6.  Patients received: ◦ premedicated, Midazolam ◦ Induced, fentanyl and propofol ◦ Vecuronium or cisatracurium ◦ Isoflurane, O 2, N 2 O (2 unshunted and 1 shunted pts) or air, and remifentanil infusion ◦ All patients received phenylephrine to maintain stable arterial pressure (no higher than 25% of normal).  Monitoring: ◦ A-line, rSO 2 by INVOS 5100B, optodes, placed by a single researcher

7.  After carotid cross-clamping, FIO 2 and minute ventilation (constant TV) were adjusted by changing RR to achieve: 1)FIO 2 30%, PETCO 2 30-35mm Hg 2)FIO 2 100%, PETCO 2 30-35mmHg 3)FIO 2 100%, PETCO 2 40-45mmHg  rSO 2 was measured after at least 5 minutes, once rSO 2 had stabilized.  Data for shunted pts were recorded after shunts were in situ and open.  A paired samples T-test was used to detect changes in rSO 2, P <0.05 were considered statistically significant.

8.  Demographic data: ◦ Mean percentage stenosis in the non-operative side was significantly higher in the shunted patient.56.4 % vs. 26.7% (p=0.026) ◦ Baseline rSO 2 varied widely (36-71%).

9. Shunted GroupUnshunted Group Operative (%) Non- operative (%) Operative (%) Non- operative (%) 100% FIO 2 Low PETCO 2 +4 +8+6 P0.0080.0110.0080.011 100% FIO 2 High PETCO 2 +3+4+6+5 P0.0180.0070.0080.024

10.  Provides statistically significant data regarding effect of FIO 2 and PETCO 2 on rSO 2 in patients undergoing CEA with general anesthesia where paucity of data is available.  Observation ◦ Unshunted group seems to show greater decrease at cross-clamp and greater increase at each measurement of rSO 2 on operative side than shunted. ◦ On the non-operative site, rSO 2 were higher at each measurement in unshunted group.  Thorough discussion, acknowledge weak and limited aspects of the study.

11. Although it is a pilot study…  No true control, not randomized, not blinded.  No sufficient statistical analysis methods given.  Very small sample.  Only three measurement points, no optimal PETCO 2 nor FIO 2 investigated.  Literature shows in healthy subjects rSO 2 increase with increase in PaCO 2, but authors used PETCO 2. Did not show data for the relation between these variables. PaCO 2 may be cofounding factors by directly affecting cerebral arterio/venous ratio.

12.  More possible cofounding factors; ◦ Cerebral metabolic rate and arterio/venous ratio also affect rSO 2 values, but they were not measured in this study. ◦ N 2 O causes elevated plasma homocysteine which has been associated with cardiac ischemia. ◦ Anatomical variations in the circle of Willi, oxygenation may be provided by ext carotid or collaterals. INVOS devices are predominantly related to internal carotid artery flow.

13.  Measurement of cerebral oxygenation problems; ◦ Low positive predictive value in detecting cerebral ischemia. ◦ Near infrared light penetrates only 3mm measuring only gray matter. ◦ Inherent intrapatient and interpatient variability in rSO 2. (need for blind study). ◦ Wide range of baseline rSO 2.

14.  Does not provide the data showing relationship between rSO 2 and neurological deficit.  Is this clinically significant? ◦ One study 2 using INVOS 5100B monitor showed the cutoff value for prediction of neurologic deterioration was 20-25% rSO 2 decrease. Based on the finding, reversing neurological deficit with increases of 3-8% in rSO 2 is questionable.

15.  Authors agree clinical significance is unclear, but suggest increasing FIO 2 to 100% for a short period is justified and recommended.

16. 1. Picton P, Chambers J, Shanks A, Dorje P. The Influence of Inspired Oxygen Fraction and End-Tidal Carbon Dioxide on Post-Cross-Clamp Cerebral Oxygenation During Carotid Endarterectomy Under General Anesth Analg. 2010;110:581-587. 2. Leteurnier, Y.; Lagadec, H.; Goueffic, Y.; Rozec, B.; Blanloeil, Y. Detection of cerebral ischemia during carotid endarterectomy in patients under general or regional anesthesia: evaluation of the new monitor Invos 5100B: 3AP5-7. European Journal of Anaesthesiology. 2007;24:25.