The Influence of Inspired Oxygen Fraction and End-Tidal Carbon Dioxide on Post-Cross-Clamp Cerebral Oxygenation During Carotid Endarterectomy Under General Anesthesia1 Akiko Inoue, DO 2/17/2010

Overview 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 (FIO2) Regional oxygenation (rSO2) has been shown to improve by increasing FIO2.

Overview In healthy subjects, both middle cerebral flow velocity and rSO2 increase with increase in PaCO2. 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 rSO2 and estimates balance between cerebral O2 supply and demand.

Overview Hypothesis: Methods: To determine whether increases in the FIO2 or PETCO2 correlate to a significant change in rSO2 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.

Methods Patients received: Monitoring: premedicated, Midazolam Induced, fentanyl and propofol Vecuronium or cisatracurium Isoflurane, O2, N2O (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, rSO2 by INVOS 5100B, optodes, placed by a single researcher

Methods After carotid cross-clamping, FIO2 and minute ventilation (constant TV) were adjusted by changing RR to achieve: FIO2 30%, PETCO2 30-35mm Hg FIO2 100%, PETCO2 30-35mmHg FIO2 100%, PETCO2 40-45mmHg rSO2 was measured after at least 5 minutes, once rSO2 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 rSO2, P <0.05 were considered statistically significant.

Summary 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 rSO2 varied widely (36-71%).

Summary Shunted Group Unshunted Group Operative (%) Non-operative (%) 100% FIO2 Low PETCO2 +4 +8 +6 P 0.008 0.011 High PETCO2 +3 +5 0.018 0.007 0.024

Critiques Provides statistically significant data regarding effect of FIO2 and PETCO2 on rSO2 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 rSO2 on operative side than shunted. On the non-operative site, rSO2 were higher at each measurement in unshunted group. Thorough discussion, acknowledge weak and limited aspects of the study.

Critiques 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 PETCO2 nor FIO2 investigated. Literature shows in healthy subjects rSO2 increase with increase in PaCO2, but authors used PETCO2. Did not show data for the relation between these variables. PaCO2 may be cofounding factors by directly affecting cerebral arterio/venous ratio.

Critiques More possible cofounding factors; Cerebral metabolic rate and arterio/venous ratio also affect rSO2 values, but they were not measured in this study. N2O 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.

Critiques 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 rSO2. (need for blind study). Wide range of baseline rSO2.

Critiques Does not provide the data showing relationship between rSO2 and neurological deficit. Is this clinically significant? One study2 using INVOS 5100B monitor showed the cutoff value for prediction of neurologic deterioration was 20-25% rSO2 decrease. Based on the finding, reversing neurological deficit with increases of 3-8% in rSO2 is questionable.

Critiques Authors agree clinical significance is unclear, but suggest increasing FIO2 to 100% for a short period is justified and recommended.

References 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. 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.