Effects Of Remimazolam On EEG Alpha Band Activity And Postoperative Cognitive Function In Elderly Patients Undergoing Lower Extremity Fractures Surgeries

ObjectiveAs a new,ultra-short-acting benzodiazepine sedative,remimazolam has the characteristics of rapid onset of action and metabolism,with high security,and is less likely to accumulate,with wide use in clinical practice.Previous studies have shown that it can be used for procedural sedation and general anesthesia induction and maintenance safely and effectively.In animal experiments in rats,the investigators found that remimazolam has less adverse effects on cognitive function than midazolam.Previous clinical studies found that remimazolam could produce certain effects on brain waves activities.The decrease in EEG alpha band density has a significant impact on the incidence of postoperative cognitive dysfunction(POCD).The purpose of this study was to use remimazolam in general anesthesia induction and maintenance in elderly patients undergoing lower extremity fracture surgery and to investigate the effects on brain wave alpha band activity and POCD,as well as the effects of remimazolam on hemodynamics and other perioperative indicators,to provide a basis for the rational application of remimazolam in general anesthesia.MethodsSeventy patients undergoing elective endotracheal intubation for general anesthesia for lower extremity fracture surgeries were randomly divided into two groups(n=35):remimazolam group(study group,Group R)and midazolam group(control group,Group C).All patients were routinely monitored for electrocardiograph(EEG),blood pressure(BP)and pulse oxygen saturation(SpO2)after admission,and ultrasound-guided nerve blocks were performed according to the site of the fracture and the surgical procedure.After completion of the nerve block,all the patients were fitted with an electroencephalogram(EEG)cap(BM-5010,Wuhan Gretek Co.),which was connected with Arc EEG acquisition system(Cadwell industries,USA).Group R was induced with remimazolam methylphenidate 0.1 mg/kg intravenously injected within the time of 1 min,followed by continuous intravenous infusion of 0.1 mg·kg-1·h-1 until the end of surgery.Group C was induced with midazolam 0.05 mg/kg intravenously injected within the time of 1 min,followed by continuous intravenous infusion of saline 0.1 ml·kg-1·h-1.After that,general anesthesia induction was continued with propofol 1～1.5 mg/kg,sufentanil 0.1～0.3 μg/kg and rocuronium 0.6 mg/kg intravenously injected.An endotracheal tube was inserted after muscle relaxation,and was connected with an anesthesia machine for mechanical ventilation.The anesthesia machine initial settings were as the follows:inhalation oxygen concentration 60%,tidal volume 6-8 ml/kg,respiratory rate 12-14 breaths/min,inspiratory-to-expiratory ratio 1:(1.5-2.0),PETCO235-45 mmHg(1 mmHg=0.133 kPa)with ventilation parameters adjustment.The anesthesia was maintained with propofol 4～10 mg·kg-1·h-1,remifentanil 0.2～0.5 μg·kg-1·min-1 intravenous infusion and sevoflurane inhalation of 0.7 alveolar minimum effective concentration(MAC).Intermittent intravenous rocuronium bromide was injected to maintain moderate muscle relaxation.The demographics including age,gender,American society anesthesiologists(ASA)classification,education,and body mass index(BMI),were recorded.The changes of frontal EEG alpha band power were recorded.Mean arterial pressure(MAP)and heart rate(HR)were recorded at 3 min rest after radial arterial puncture(T1),immediately after general anesthesia induction(T2),immediately after endotracheal intubation(T3),at the beginning of surgery(T4),30 min after the beginning of surgery(T5),at the end of surgery(T6),and at 30 min after entering PACU(T7).IL-6,IL-10,and S100-β concentrations were detect and recorded at 1d preoperatively(T0),24 h postoperatively(T8),and 72 h postoperatively(T9).The Mini-mental State Examination(MMSE)scores were recorded at T0,T8,T9,5 d(T10),and 7 d postoperatively(T11).Duration of anesthesia,surgery and PACU stay were recorded,respectively.Fluid intake,bleeding volume and urine output were also recorded.The dosages of propofol,remifentanil,sufentanil and perioperative adverse events and vasoactive drug use were recorded,too.Results(1)Comparisons of the demographics and perioperative indicators between the two groupsThere were no statistically significant differences in the demographics,including age,gender,ASA classification,education,and BMI,between the two groups(P>0.05).The perioperative related indicators,including fracture site,surgery method,fluid intake,bleeding volume,urine output,anesthesia duration,operation duration,PACU retention time,the consumption of propofol,sufentanil,and remifentanil,were no significant differences between the two groups(P>0.05).(2)Comparison of intraoperative frontal alpha band power between the two groupsCompared with Group C,patients in Group R had significantly higher intraoperative frontal alpha band mean power spectral density(P<0.001).(3)Comparisons of MMSE scores and the incidence of POCD between the two groupsCompared with T0,the MMSE scores were significantly lower at T8 and T9 in Group R,and at T8,T9 and T10 in Group C(P<0.05).The differences between the MMSE scores of the two groups at T0 were no significant(P>0.05).Compared with Group C,the MMSE scores were significantly higher and the incidences of POCD were significantly lower at T8 and T9 in Group R(P<0.05).(4)Comparisons of blood indicators in the two groupsCompared with T0,IL-6,IL-10,and S100-β concentrations were significantly higher at T8 and T9 in both groups(P<0.05).There were no statistically significant differences in the values of IL-6,IL-10 and S100-β concentrations between the two groups at T0(P>0.05).Compared with Group C,IL-6 concentrations at T8,S100-β concentrations at T8 and T9 were significantly lower in Group R(P<0.05),and IL-10 concentration at T8 was significantly higher(P<0.05)in Group R.(5)Comparisons of perioperative hemodynamics between the two groupsCompared with T1,MAP was significantly lower in both groups from T3 to T7(P<0.05),HR was significantly higher at T2 and T3(P<0.05)and significantly lower at T5(P<0.05)in Group C,and was significantly lower from T4 to T7 in Group R(P<0.05).There were no statistically significant differences in MAP and HR between the two groups at T1(P>0.05).Compared with Group C,MAP was significantly higher and HR was significantly lower at T5 and T6 in Group R(P<0.05).(6)Comparisons of perioperative adverse events and use of vasoactive drugs between the two groupsThere were no severe hypotension and severe bradycardia occurred in both groups.The incidence of bradycardia and the use of atropine between the two groups were not statistically significant(P<0.05).Compared with Group C,the incidence of hypotension and postoperative respiratory depression and the use of ephedrine and phenylephrine were significantly lower in Group R(P<0.05).ConclusionsIn this study,remimazolam could increase frontal EEG alpha band power spectral density,reduce cognitive function impairment,and reduce the incidence of POCD in elderly patients undergoing lower extremity fractures surgery,without significant effects on intraoperative hemodynamics,and with no serious complications occurred.