Orexinergic neuron gene polymorphisms affect the sleep-wakefulness
transition and hemodynamic stability during propofol, dexmedetomidine
and remifentanil anesthesia
Abstract
Aim: Propofol-remifentanil-dexmedetomidine-based total intravenous
anesthesia is widely used, but ensuring the safety of the
sleep-wakefulness transition and hemodynamic stability remains a
challenge. This study aimed to investigate the influence of orexinergic
neuron gene polymorphisms on interindividual variability in the time to
loss of consciousness (LOC), time to wake, and cardiovascular
fluctuations. Methods: A total of 250 patients were included in the
study. Gene polymorphisms were detected using the Agena Bioscience
MassARRAY system. Anesthesia induction began with propofol and
maintained with propofol and remifentanil. Dexmedetomidine was
administered before anesthesia induction. The time to LOC, time to wake,
heart rate (HR), and mean arterial pressure (MAP) were documented.
Results: HCRTR2 rs2292040 and rs76380807 were significantly associated
with the time to LOC, and HCRTR2 rs7774031 was correlated with the time
to wake. HCRTR2 rs3122162, rs3122169, and rs74296544 were correlated
with HR fluctuations, and HCRTR1 rs2176807, rs2271933, rs871634, and
HCRTR2 rs74296544 were associated with MAP fluctuations. Multiple linear
regression analysis revealed that a TCI concentration of propofol
> 4 μg ml-1 at the time of LOC and dexmedetomidine were
influencing factors for the time to LOC, whereas HCRTR2 rs7774031
influenced the time to wake. Baseline HR, baseline MAP, dexmedetomidine,
HCRTR2 rs3122162, and HCRTR1 rs2176807 were predictive factors for
cardiovascular susceptibility. The predictive models for the time to
LOC, time to wake, HR, and MAP fluctuations accounted for 41.89%,
3.36%, 35.56%, and 47.41% of variations, respectively. Conclusion:
Genetic variants of orexinergic neurons may affect sleep-wakefulness
transition and hemodynamic stability during propofol, dexmedetomidine,
and remifentanil anesthesia.