Studies have shown that the cerebral cortex is particularly vulnerable to hypoperfusion[19]. Our study investigated the effects of nicardipine-induced hypotension on regional cerebral blood flow and oxygenation in the cerebral cortex using O2C. The study found that alterations in rCBF and rSO2 were in line with changes in MAP during mild to severe hypotension. Additionally, the decrease in rSO2 was significantly greater than that of rCBF. There were strong correlations observed between rCBF and rSO2, as well as between MAP and both rCBF and rSO2 throughout the entire hypotension process. Furthermore, it was observed that HR and SpO2 decreased during nicardipine-induced hypotension. Although the difference was statistically significant, it was not clinically significant. No drug tolerance was observed during the hypotension process. MAP and other indicators recovered for a long time after drug withdrawal. However, cerebral blood flow and cerebral oxygen did not fully recover to the baseline values after blood pressure recovery.
During controlled hypotension, cerebral hypoperfusion may lead to postoperative neurological damage, such as stroke and perioperative neurocognitive dysfunction[20]. Therefore, it is critical to maintain appropriate cerebral perfusion for a good prognosis. Zhang et al.[21] evaluated cerebral perfusion during nicardipine-induced hypotension by using regional cerebral oxygen saturation measured through near-infrared spectroscopy. When MAP decreased by 30%, rSO2 decreased by only approximately 5% from baseline. This finding is similar to the results of our study, in which rSO2 decreased by approximately 6% when the baseline MAP was reduced by 30%. ChoiSH et al.[7] used rSO2 to evaluate cerebral perfusion. The results showed that under normal hematocrit (HCT) conditions, controlled hypotension with a target MAP of 60 to 65 mmHg (about 25% lower than the baseline MAP) did not affect rSO2. However, in our study, rSO2 decreased slightly (approximately 2%) even when the baseline MAP decreased by 20%. Kimme et al.[19] achieved controlled hypotension through vena cava occlusion and measured changes in regional cerebral blood flow (rCBF) using a laser Doppler blood flow meter. The results showed that when the baseline MAP decreased by 50%, rCBF decreased by 55% from baseline. However, our study found that rCBF only dropped by 19.5%. We attribute this difference to the dilating effect of nicardipine on cerebral vessels.
The antihypertensive drug utilised in our study was nicardipine. As an L-type dihydropyridine calcium channel blocker, it partially acts on the voltage-dependent calcium channel on the cell membrane. This inhibition of Ca2 + influx inhibits cerebral vasoconstriction, improves cerebral blood flow[22], and protects neurons by preventing intracellular calcium overload[23]. Additionally, nicardipine effectively reduces cerebral oxygen metabolism and improves cerebral oxygenation. In this study, it was found that the use of nicardipine for mild to severe hypotension resulted in a decrease in both rCBF and rSO2, showing a similar trend. The decrease in rCBF was directly associated with the effect of nicardipine, which significantly attenuates cerebral autoregulation (CA)[7]. The dysfunction of CA caused by nicardipine may be related to its strong dilating effect on cerebral arterioles[24]. The decrease in rSO2 was related to the oxygen supply and consumption of local brain tissue, as well as FiO2[25] and PaCO2[26]. Our study showed that the decrease in rSO2 was also related to the decrease of MAP. Although CO2 has a significant impact on rCBF and rSO2, PaCO2 was maintained within a stable range of 35-45mmHg during the experiment. Additionally, nicardipine does not affect CO2 reactivity[27], which minimises the influence of CO2 on rCBF and rSO2. It has been reported that maintaining the minimum alveolar concentration (MAC) of sevoflurane between 0.3 and 1.5 does not affect cerebrovascular reactivity in healthy individuals[28], and that the concentration of sevoflurane also has no effect on rCBF and rSO2[29]. In our study, the MAC was within this range. Classical CA was not observed during controlled hypotension, possibly because nicardipine significantly weakens the autonomic regulation of cerebral blood flow[7].After drug withdrawal, the time for blood pressure to return to baseline was prolonged, which may be related to the longer half-life of nicardipine[30]. Continuous infusion may lead to the prolongation of elimination half-life of nicardipine, which may require intervention with fluid replacement or the use of calcium or vasopressors[27].
In addition, cerebral hypoxia is defined as a decrease in rSO2 of more than 20% from baseline[9].In this experiment, the relative change of rSO2 in severe hypotension is close to 20%, which does not meet the above standard, and it is relatively safe for healthy patients without underlying diseases. But a sharp decline of Hb caused by intraoperative blood loss and hemodilution and the existence of cerebrovascular diseases may lead to higher risk of cerebral ischemia and hypoxia.Therefore, for these patients, mild to moderate hypotension during the operation can be beneficial for ensuring safety and improving postoperative recovery.
However, this experiment has certain limitations. Firstly, it is important to note that although PaCO2 was controlled within the normal range, studies have shown that rCBF can increase or decrease by 2%-4% for every 1mmHg change in PaCO2[29].Secondly, we did not measure brain damage markers such as neuron-specific enolase (NSE) and S-100β protein in our study to support our results. Furthermore, it is necessary to validate our findings in clinical practice.
During the use of nicardipine for intraoperative controlled hypotension, both rCBF and rSO2 decrease progressively as the degree of hypotension increased. However, the decrease in rSO2 is significantly greater than that of rCBF. During mild to moderate hypotension, rSO2 decreases by less than 10%, which is less likely to cause cerebral ischemia and hypoxia, and has a protective effect on the brain under anesthesia. Severe hypotension is safer for relatively healthy patients without underlying diseases, but poses a significant risk of cerebral ischemia and hypoxia for patients with pre-existing cerebrovascular diseases.