Protective Effect Of Dexmedetomidine On Brain In Patients Undergoing Brain Tumor Surgery

Survival time of patients undergoing brain tumor surgery is prolonged and their postoperative quality of life is extensively concerned with the advances in surgical techniques.The recovery of postoperative cognitive function is of great importance for improving the postoperative quality of life of patients with brain tumors.However,studies have shown that the incidence of postoperative cognitive dysfunction（POCD）in patients with brain tumors is as high as29-90%.How to promote the recovery of postoperative cognitive function in patients undergoing brain tumor surgery is one of the focuses in medical research over recent years.The occurrence of POCD in patients with brain tumors is closely related to the location,size and nature of the tumor.Pathophysiological changes caused by tumor compression and invasion of brain tissue,including cerebral ischemia,hypoxia,edema and intracranial hypertension,may impair the cognitive function of patients and brain injury can be additionally aggravated by perioperative trauma,circulatory fluctuation,ischemia-reperfusion,inflammatory response and oxidative stress,resulting in a further decrease in postoperative cognitive function.Active intervention in the pathophysiology process of brain injury by neuroprotective measures and drugs during the perioperative period can provide an important tool to reduce the incidence of POCD for patients undergoing brain tumor surgery.Dexmedetomidine（Dex）is a novel highly selectiveα₂-adrenergic receptor agonist and widely applied in clinical practice due to its unique pharmacological properties of sedative,analgesic,anti-sympathetic effects.Substantial evidence has proved in recent years that Dex alleviates the cerebral ischemia/reperfusion injury,reverses the neurotoxicity induced by anesthetics,and promotes the recovery of brain function via the anti-inflammatory,anti-oxidative stress,and anti-apoptosis signaling pathways,suggesting that Dex may serve as a new option for perioperative cerebral protection in patients undergoing brain tumor surgery.It has been reported that application of Dex in craniocerebral surgery can reduce the dosage of anesthetics needed,maintain perioperative hemodynamic stability,and improve postoperative analgesia.On this basis,effect of Dex on the recovery of postoperative cognitive function was further investigated in the present study using instruments such as QoR-15,MMSE,MoCA scales and the effect of Dex on the expression of brain injury markers,including S100β,NSE and GFAP,inflammatory factors,including IL-6 and TNF-α,and oxidative stress indexes,including SOD and MDA,was explored,hopefully to provide theoretical and experimental basis for perioperative cerebral protection in patients with brain tumor.PART 1 EFFECT OF DEXMEDETOMIDINE ON POSTOPERATIVE RECOVERY QUALITY IN PATIENTS UNDERGOING BRAIN TUMOR SURGERYObjective To investigate the effect of dexmedetomidine on perioperative hemodynamics,postoperative pain and postoperative recovery quality in patients undergoing brain tumor surgery.Methods This was a prospective,double-blinded,randomized,controlled study.A total of 60 patients aged 19-62 years（ASA I-III）who underwent scheduled supratentorial tumor surgery under general anesthesia were selected and randomly divided into the Dex treatment group（Group D）and the control group（Group C）,with 30 cases in each group.After anesthesia was induced and stable circulation was achieved,patients in Group D were continuously given0.4μg/kg?h Dex infusion till the end of the operation and those in Group C received saline infusion.Patients in both groups were induced with total intravenous general anesthesia by TCI of propofol and remifentanil and BIS40-60 was maintained during the operation with vital signs in the normal range.Changes in mean blood pressure（MAP）and heart rate（HR）before the induction（T0）,10 mins after tracheal intubation（T1）,skull pin placement（T2）,scalp incision（T3）,skull drilling（T4）,30 mins after dura mater incision（T5）,at the end of surgery（T6）,and extubation（T7）were observed and recorded for patients in the two groups,and intraoperative adverse reactions as well as the use of anesthetic and vasoactive drugs were recorded.Postoperative pain was evaluated by visual analogue scale（VAS）1 day before the operation and on Days 1,2,3 and 7 after the operation,respectively,and postoperative quality of recovery was evaluated by QoR-15 scale.Results A total of 55 patients（27 in Group C and 28 in Group D）completed the study and finally were included in the statistical analysis.No significant differences in the general data were noted between the two groups before and during the operation（P>0.05）.The use of anesthetics,including propofol,remifentanil,and fentanyl in Group D was significantly less than that in Group C（P<0.05）.Comparison of MAP between the two groups showed that MAP at each time point between T2 and T7 was significantly decreased in Group D compared with that of Group C,respectively（P<0.05）;compared with T0,MAP at T7 was significantly increased in Group C（P<0.05）,and remained unchanged in Group D（P>0.05）;compared with T1,MAPs at T2,T3,and T6were significantly increased in Group C（P<0.05）,and no significant changes were observed in Group D at each time point（P>0.05）.HR comparison between the two groups indicated that HP at each time point between T2 and T7 was significantly decreased in Group D compared with that of Group C,respectively（P<0.05）;compared with T0,HR at T7 was significantly increased in Group C（P<0.05）and no significant change was observed in Group D（P>0.05）.Compared with Group C,the incidence of intraoperative tachycardia and hypertension,the use of vasoactive drugs such as esmolol and urapidil,and the blood loss were decreased significantly in Group D（P<0.05）.Comparison of postoperative pain between the two groups demonstrated that VAS scores on Day 1 and 2 after the operation as well as the use of postoperative analgesic drugs were significantly reduced compared with that of Group C,respectively（P<0.05）.The postoperative quality of recovery was compared between the two groups and showed that the QoR-15 scores on Day 1 and 2 after the operation were significantly increased（P<0.05）and the incidence of postoperative adverse reactions,such as nausea and vomiting,tachycardia and hypertension,were significantly decreased（P<0.05）in Group D compared with Group C.Dimension analysis of QoR-15 scales showed that the postoperative quality of recovery in Group D was superior to Group C within 2 days after the operation in recovery quality of emotional state,physical comfort,and pain（P<0.05）.Conclusions 1.Dex applied in brain tumor surgery reduces the use of intraoperative anesthetics and intraoperative blood loss,and can help maintain hemodynamic stability during the operation.2.Dex reduces postoperative pain and the occurrence of postoperative adverse reactions as well as the use of analgesic drugs after the operation in patients undergoing brain tumor surgery.3.Dex improves the postoperative quality of recovery in patients undergoing brain tumor surgery in terms of the emotional state,physical comfort and pain.PART 2 PROTECTIVE EFFECT OF DEXMEDETOMIDINE ON BRAIN IN PATIENTS UNDERGOING BRAIN TUMOR SURGERYObjective To investigate the protective effect and the possible mechanism of dexmedetomidine on brain in patients undergoing brain tumor surgery.Methods A total of 60 patients aged 19-62 years（ASA I-III）who underwent scheduled supratentorial tumor surgery under general anesthesia were selected and randomly divided into the Dex treatment group（Group D）and the control group（Group C）,with 30 cases in each group.After anesthesia was induced and stable circulation was achieved,patients in Group D were continuously given 0.4 μg/kg?h Dex infusion till the end of the operation and those in Group C received saline infusion.Patients in both groups were induced with total intravenous general anesthesia by TCI of propofol and remifentanil and BIS 40-60 was maintained during the operation with vital signs in the normal range.Expression levels of brain injury markers（S100β,NSE,and GFAP）,inflammatory factors（IL-6 and TNF-α）,and oxidative stress indexes（SOD and MDA）were detected before the induction（T0）,30 mins after dura mater incision（T5）,at the end of surgery（T6）,Day 1（T8）,Day 2（T9）,and Day 3（T10）after the operation.Postoperative delirium was evaluated with CAM-ICU scale within 3 days after the operation and postoperative cognitive function was assessed with MMSE and Mo CA scales on Days 1,3,and 7 after the operation.The incidence rate of POCD was then compared between the two groups.Results A total of 55 patients（27 in Group C and 28 in Group D）completed the study and were included in the statistical analysis.No significant differences in the general data were noted between the two groups before and during the operation（P>0.05）.Comparison of neurological function between the two groups showed that the incidence of postoperative delirium was significantly decreased within 3 d after the operation（P<0.05）,and scores of MMSE and Mo CA were significantly increased on Day 3 and Day 7 after the operation（P<0.05）in Group D compared with those of Group C,respectively.Scores of Mo CA subscales indicated that Group D was better than Group C mainly in three dimensions including visual space/execution ability,delayed memory and attention（P<0.05）.According to the diagnosis criterion for POCD （>1 SD simultaneous decrease in postoperative MMSE and Mo CA scores）,the incidence of POCD in Group D on Day 3 after the operation was significantly reduced compared with that of Group C（P<0.05）.Comparison of expression levels of brain injury markers between the two groups indicated that serum level of S100β was significantly increased at T5,T6,T8,T9,and T10（P<0.05）and levels of GFAP and NSE were significantly increased at T6,T8,T9,and T10（P<0.05）in both groups compared with T0;and the concentration of serum S100β was decreased significantly at T5,T6,T8,and T9 and those of NSE and GFAP were significantly decreased at T6,T8,and T9 compared with Group C（P<0.05）.Expression of Inflammatory factors were compared between the two groups and showed that concentrations of serum IL-6 and TNF-α were significantly increased at T5,T6,T8,T9 and T10 in both groups compared with T0（P<0.05）,respectively;and concentrations of serum IL-6 and TNF-α were significantly decreased at T6,T7,T8,and T9 in Group D when compared with Group C（P<0.05）.Comparison of oxidative stress indexes between the two groups showed that SOD activity was significantly reduced at T5,T6,T8,and T9（P<0.05）and the concentration of MDA was significantly increased at T5,T6,T8,and T9（P<0.05）in both groups compared with T0;and SOD activity was significantly increased at T6 and T8（P<0.05）and the concentration of MDA was significantly reduced at T5,T6,T8,and T9（P<0.05）in Group D when compared with Group C.Conclusions 1.Dex applied in brain tumor surgery improves the score of postoperative cognitive function 7 days after the operation and reduces the incidence of postoperative POCD and delirium 3 days after the operation,which may contribute to the postoperative recovery of brain function;2.Inflammatory response and oxidative stress may be involved in brain injury caused by brain tumor surgery;3.Dex can reduce the expression of brain injury markers and inhibit inflammatory response and oxidative stress,suggesting that Dex may protect brain by inhibiting inflammatory response and oxidative stress.