Clinical Trial Of Dexmedetomidine Or Lidocaine On The Protection Of Spinal Cord Injury Durring Vertebral Colum Surgery

BACKGROUD AND OBJECTIVESSpinal disease can seriously affect the function of the body as a whole. Its treatment is comprehensive strategy and surgery is the most popular one.In the last decades, with the development of the medical technology and the improvement of the internal fixation instruments, number of spinal surgery increased very quickly. But during the spinal procedures, the spinal cord and nerve might be damaged due to many factors. Spinal decompression and internal fixation instruments all might lead to spinal injury which would result in a decline of living quality to patients postoperatively,even paralysis. So, It is very important to monitor the spinal cord function and take measures to protect the spinal and the nerves. Dexmedetomidine is a potent and highly selective agonist of α2-adrenergic receptors with a broad spectrum of effects, including clinical sedation, anesthetic sparing effects, and analgesia. Recent experimental works indicated that dexmedetomidine exhibits neuroprotection through a2-adrenergic receptors. Animal experiments also proved its spinal cord protection. Lidocaine intravenous application has analgesic and anti-inflammatory effects, basic research also suggests that it plays a protective role in spinal cord reperfusion injury. Whereas, there was little report of clinical research about this subject. It was unclear if these two medicines had spinal cord protection effect. In addition, intraoperative spinal cord function monitoring is an useful mean of preventing spinal cord injury and is helpful to reduce neural complications. The combined neurophysiologic monitoring had been taken as the main measure to detect spinal cord injury. But it was susceptible to narcotic drugs. Although dexmedetomidine and lidocaine have the drug thrifty effect during general anesthesia and would alleviate the unfavorable impact of other anethetics, but it was unknown if itself would affect the spinal cord function monitoring in Chinese.Therefore, the first purpose of this study was to detect if dexmedetomidine and lidocaine would affect the neurophysiologic monitoring and the safety dosage. On the basis of the previous study, we hope to find whether these two medicines of safe dosage plays a protective role in spinal surgery.METHODS The first part:Effect of dexmedetomidine or lidocaine on the neurophysiologic monitoring in patients undergoing lumber vertebral surgery.96patients scheduled for lumber vertebral surgery under general anesthesia were enrolled in this study. They were divided into three groups randomly using envelope method:dexmedetomidine group (group D), lidocaine group (group L) and control group (group C) with32cases each. Induction was proceeded by propofol and remifentanil by TCI model. Cisatracurium was facilitated for laryngeal mask airway intubation. After the patient was rotated to prone position, dexmedetomidine0.6μg/kg of loading dose (in10min) was given in group D, followed by0.2μg/kg/h infusion rate. After30min, the infusion rate was increased to0.4μg/kg/h and0.6μg/kg/h step by step. Each infusion rate were kept for30min and then increased. Lidocaine infusion was given in group L with a loading dose of1.5mg/kg (in10min) and then followed by lmg/kg/h infusion rate. After30min, the infusion rate was increased to1.5mg/kg/h and2.0μg/kg/h step by step. Each infusion rate were kept for30min and then increased. The same amount of saline was given in group C. Anesthesia was maintained with propofol and remifentanil. Cisatracurium was infused by0.1-0.2mg/kg/h continuously intraoperatively. Somatosensory of median nerve and posterior tibial nerve, and motor-evoked potentials of thumb abductor muscle and thumb short abductor muscle were monitored on time points as follows:before induction of anesthesia (TO), before the start of infusion test drugs (T1), the end of the loading dose infusion (T2), the end of the first maintenance doses (T3), the end of the second doses(T4) and the end of the third doses(T5). Recorded the effect-site concentration of propofol and remifentanil on all time points and the total amount infused of the two drugs. The awake time and agitation after operation were also recorded.The second part:Effect of dexmedetomidine or lidocaine on the spinal cord injury in patients undergoing cervical spinal surgery69patients scheduled for cervical spine surgery under general anesthesia were enrolled in this study. They were divided into three groups randomly using envelope method:dexmedetomidine group (group D), lidocaine group(group L) and control group (group C) with23cases each. Anesthesia induction was proceeded with etomidate, sufentanil and cisatracurium. Anesthesia was matained maintained with propofol and remifentanil. Cisatracurium was infused by0.1-0.2mg/kg/h continuously intraoperatively. After the patient was positioned, dexmedetomidine0.6μg/kg of loading dose (in lOmin) was given in group D, followed by0.4μg/kg/h infusion rate. Lidocaine infusion was given in group L with a loading dose of1.5mg/kg (in10min) and then followed by2mg/kg/h. The same amount of saline was given in group C. Somatosensory of median nerve and posterior tibial nerve, and motor-evoked potentials of the contralateral thumb adduction muscle and posterior tibial muscle were monitored. Electromyography was also monitored and the position of the record electrode was considered according to the segment of the cervical surgery. Venous blood was collected on time points as before induction,1h after the operation,6h after the operation,24,48and72h after the operation. Glial fibrillaryacidic protein(GFAP), matrix metalloproteinases(MMPs)-9and nearo specific enolase(NSE) were detected by enzyme linked immunoabsorbant assay (ELISA). Tumor necrosis factor(TNF)-a, interleukin-6(IL-6) and interleukin-8were detected by raioimmunoassay. Sensation of the skin and muscle strength of upper and lower limbs Japanese orthopaedic association score were measured and compaired before and after surgery.RESULTS The first part:Effect of dexmedetomidine or lidocaine on the neurophysiologic monitoring in patients undergoing lumber vertebral surgery.93patients completed this study. No significant differences were observed in these there groups (P>0.05). There were no significant differences in latency and amplitude of somatosensory evoked potentials of the median nerve and posterior tibial nerve between T1and T2, T3, T4in group D (P>0.05). However, on time point of T5, the amplitude dropped down and the latency extended respectively(P<0.05). Otherwise, there were no significant differences in the amplitude and latency of somatosensory evoked potentials of the median nerve and posterior tibial nerve between T1and other time points in group L (P>0.05). Neither in group C (P>0.05); Compared with T1, there were no difference in amplitude of the motor evoked potentials of abductor pollicis brevis and hallux abductor on time points of T2、T3、 T4in group D (P>0.05). But the amplitude decreased on T5(P<0.05)。However, no significant difference were found in group L and group C on all time points(P>0.05).The effect-site concentration of propofol and remifentanil of group D were significantly higher at T1than at T2and T5(P<0.05). No significant differences were found between T1,T3, T4and T5(P>0.05); In group C, the effect-site concentration of propofol and remifentanil were significantly lower at T1and T2than at T3, T4and T5(P<0.05). The total dosage of propofol and remifentanil were significantly higher in group C than in group D (P<0.05). There were no significant differences in the awake time and agitation between the three groups.The second part:Effect of dexmedetomidine or lidocaine on the spinal cord injury in patients undergoing cervical spinal surgery62cases (22in group C,20in group D,20in group L) completed this study. A total number of14cases(4cases in group D,5cases in group L and C)were found of neurophysiologic monitoring alarm during the procedure. No statistic significance was found between groups (P>0.05). Serum concentration of GFAP increased significantly on time points T6and T7in all the patients, comparing with TO (P<0.05). Otherwise, lower concentration was found in group D (P>0.05). Serum concentration of MMP-9increased significantly on time points in group L and C (P<0.05), but not in group D. Serum concentration of NSE increased only on time point of T7(P<0.05) and the concentration in group D was lower than the other two groups (P<0.05). Serum concentration of TNF alpha increased on time points of T5, T6and T7in all groups (P<0.05). The highest concentration was found on time point of T6(P<0.01). Concentration in group D were lower than the other two groups on T6and T7(P<0.05). IL-8increased on time points of T5, T6, T7and T8in all groups. The highest concentration was found in group C on T5. Concentration of group C and L,but not in group D, was still higher on T6. IL-8also increased after the operation and decreased to the normal level until72h postoeratively. Lower concentration was found in group D on time points of T5and T6. There were no significant difference of sensation and strength variation perioperatively between groups. JOA score of the three groups after increased significantly on the seventh day and no significant difference was found between groups.CONCLUSION1. Our result demonstrated that dexmedetomidine would not affect the somatosensory and motor-evoked potentials in patients undergoing spinal surgery if the doses was considered. A loading dose of0.6μg/kg followed by0.2-0.4μg/kg/h could be used in propofol and remifentanil anesthesia in spinal surgery. But0.6μg/kg/h infusion rate should be avoided.2. Lidocaine infusion can also be used in such procedures with a loaded dose of1.5mg/kg and then followed by1-2mg/kg/h infusion and didn’t affect the somatosensory and motor evoked potentials either. In additional, dexmedetomidine and lidocaine could reduce the consumption of propofol and remifentanil.3. Serum GFAP, MMP-9and the NSE increased in the early period after the spinal surgery. We thought spinal cord was damaged perioeratively in a certain degree. Inflammatory factor including TNF alpha, IL-6, IL-8elevated postoperatively, which means inflammatory reaction played a important role on spinal cord injury.4. Clinical doses of dexmedetomidine can reduce serum concentration of GFAP, MMP-9and inflammatory factor in the spinal surgery. These results implied that dexmedetomidine has certain but limited protective effect on the spinal cord. 5. Lidocaine infusion had no obvious effect on serum GFAP, MMP-9and NSE concentration, but inhibited the release of inflammatory factors in the early period after the spinal colum surgery. So we deduced that lidocaine infusion can inhibit the inflammatory reaction but has no obvious protective effect on the spinal cord injury.