Quantitative analysis of the effect of end-tidal carbon dioxide on regional cerebral oxygen saturation in patients undergoing carotid endarterectomy under general anaesthesia

Abstract

Aims: Regional cerebral oxygen saturation (rSO₂ ) is currently the most used measure in clinical practice to monitor cerebral ischaemia in patients undergoing carotid endarterectomy (CEA). Although end-tidal carbon dioxide (P_ET CO₂ ) is known as a factor that influences rSO₂ , the relationship between P_ET CO₂ and rSO₂ has not been quantitatively evaluated in patients with severe arteriosclerosis. This study aimed to evaluate the effect of P_ET CO₂ on rSO₂ in patients undergoing CEA under general anaesthesia.

Methods: The intervention to change P_ET CO₂ was conducted between skin incision and clamping of the carotid artery. The rSO₂ values were observed by changing P_ET CO₂ in the range of 25-45 mmHg. The P_ET CO₂ -rSO₂ relationship was characterized by population analysis using a turnover model.

Results: In total, 1651 rSO₂ data points from 30 patients were used to determine the pharmacodynamic characteristics. Hypertension (HTN) and systolic blood pressure (SBP) were significant covariates on the slope factor in the stimulatory effect of P_ET CO₂ on rSO₂ and fractional turnover rate constant (k_out ), respectively. The estimates of the parameters were k_out (min^-1 ): 3.59 for SBP <90 mmHg and 0.491 for SBP ≥90 mmHg, slope: 0.00321 for patients with HTN and 0.00664 for patients without HTN.

Conclusion: The presence of HTNattenuates the response of rSO₂ after a change in P_ET CO₂ . When cerebral blood flow is in a state of decline caused by a decrease in SBP to <90 mmHg, the response of rSO₂ to P_ET CO₂ is increased. It is advisable to maintain SBP >90 mmHg in patients with HTNduring CEA.

Keywords: pharmacodynamics; satherosclerosis; vascular disease.

Figure 1

Time courses of end‐tidal carbon dioxide (P_ETCO₂; A), regional cerebral oxygen saturation (rSO₂; B), fractional rSO₂ (C) and systolic blood pressure (D) during an intervention period to change P_ETCO₂ in patients undergoing carotid endarterectomy (n = 30). P_ETCO₂ is the partial pressure of CO₂ at the end of an exhaled breath. The intervention was conducted between skin incision and clamping of the carotid artery. The time at which the tidal volume and ventilation rate were decreased to raise P_ETCO₂ to 45 mmHg was defined as the reference time. The intervention period was set as the time elapsed between the reference time and the time when P_ETCO₂ reached 25 mmHg. Fractional rSO₂ was calculated by dividing rSO₂ by the individual baseline rSO₂ values. The baseline rSO₂ value was defined as the rSO₂ value at the reference time

Figure 2

Regional cerebral oxygen saturation (rSO_2, A) and fractional rSO₂ (B) vs. end‐tidal carbon dioxide (P_ETCO₂) in patients undergoing carotid endarterectomy (n = 30). P_ETCO₂ is the partial pressure of CO₂ at the end of an exhaled breath. The intervention was conducted between skin incision and clamping of the carotid artery. The time at which the tidal volume and ventilation rate were decreased to raise P_ETCO₂ to 45 mmHg was defined as the reference time. The intervention period was set as the time elapsed between the reference time and the time when P_ETCO₂ reached 25 mmHg. Fractional rSO₂ was calculated by dividing rSO₂ by the individual baseline rSO₂ values. The baseline rSO₂ value was defined as the rSO₂ value at the reference time

Figure 3

Predictive checks of the final pharmacodynamic model. A black+ indicates the observed fractional regional cerebral oxygen saturation (rSO₂). The solid red line and shaded areas indicate the 50% prediction line and 90% prediction intervals, respectively. Fractional rSO₂ was calculated by dividing rSO₂ by the individual baseline rSO₂ values. Baseline rSO₂ value was defined as the rSO₂ value at the reference time. The time at which the tidal volume and ventilation rate were decreased to raise end‐tidal CO₂ to 45 mmHg was defined as the reference time

Figure 4

The simulated response of fractional regional cerebral oxygen saturation (rSO₂) to end‐tidal carbon dioxide (P_ETCO₂) in a hypothetical patient. Based on the presence of hypertension and whether the systolic blood pressure (SBP) was above or below 90 mmHg, four different cases were simulated. P_ETCO₂ and fractional rSO₂ data from a patient (ID 12) were used for the simulation analysis. SBPs observed during the intervention period ranged between 68 mmHg and 178 mmHg. The intervention was conducted between skin incision and clamping of the carotid artery. The time at which the tidal volume and ventilation rate were decreased to raise P_ETCO₂ to 45 mmHg was defined as the reference time. The intervention period was set as the time elapsed between the reference time and the time when P_ETCO₂ reached 25 mmHg. Fractional rSO₂ was calculated by dividing rSO₂ by the individual baseline rSO₂ values. The baseline rSO₂ value was defined as the rSO₂ value at the reference time