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Epidural anesthesia can protect fibrinolytic function after surgery

王天龙^△，齐琰琴，杨拔贤，赵　磊

（北京大学人民医院麻醉科，北京　100044）

WANG Tian－long^△，QI Yan－qin，YANGBa－xian，ZHAO Lei

（Department of Anesthesia，Peking University People’s Hospital，Beijing 　100044，China）

SUMMARY

　　Objective：To study the influences of different anesthesia techniques on stress response，coagulation and fibrinolytic function.

　　Methods：Thirty patients undergoing hysterectomy were randomized into three groups：Group E （continuous epidural anesthesia，n＝10），Group G+ E （epidural anesthesia combined general anesthesia，n＝10） and Group G （general anesthesia，n＝10）. The blocking level with epidural anesthesia was maintained between T₆－L₃ with 0.75％ bupivacaine followed by Patient－Controlled Epidural Analgesia （PCEA）. General anesthesia was finished with convention followed by Patient－Controlled Analgesia（PCA）. Blood samples were taken at pre－anesthesia （T₀），the end of operation （T₁） and postoperative 24 h（T₂），72 h （T₃） to determine catecholamine concentration，coagulation and fibrinolysis variables.

 　　Results：The nonepinephrine （NE） levels in Group E and Group G+ Ewere not changed throughout the procedure，butobviously elevated in Group G （P<0.01） as compared with the baseline and those in the other Groups （P<0.05）. The epinephrine （E） levels at T₁ in all groups were markedly increased as compared with those at T₀ and peaked （P<0.01），and then returned to the baseline at T₃. Fibrinogen （FIB） levels in all groups were obviously decreased at T₁，postoperatively elevated rapidly and peaked at T₃ （P<0.01）. FIB levels at T₃ in groups G+ E and Gwere much higher than that in Group E （P<0.05）. The thrombin－anti－thrombin Ⅲcomplex （TAT） levels at T₁ in Group G + E and Gwere significantly increased as compared with those at Group E （P<0.01），and subsequently recovered to pre－anesthesia following surgery. TAT level in Group Ewas more decreased postoperatively than the baseline and those in the other groups （P<0.05）. The D－dimer level in Group E over time was remarkably increased as compared with the baseline （P<0.05），and the D－dimer levels peaked at T₂ in all groups （P<0.01）. The tissue－type plasminogen activator （t－PA） was more elevated than T₀ at T₁ （P<0.01） in all groups，and then returned to normal in Group E. But the marked decrease of t－PA in Groups G + E and Gwas revealed 72h after surgery and became much lower than that in Group E （P<0.01）. The plasminogen activating inhibitor－1 （PAI－1） in Group Gand Group G+ E was more elevated perioperatively and became higher than that in Group E （P<0.01）.<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

　　Conclusion：Epidural anesthesia can preserve fibrinolytic function after lower－abdomen surgery by the inhibitory effects on surgical stress，PAI－1 and other mechanisms. The thromboprophylactic effects are revealed only following epidural anesthesia.

　　Key words：Anesthesia，epidural；Anesthesia general；Hysterectomy；Stress；Blood coagulation；Fibrinolysis

　　There exists the complicated coagulation and fibrinolysis system in human body，and normally dynamic balance presents. If the balance is disturbed owing to some factors changed，consequently it will possibly result in potential coagulation dysfunctions，hypercoagulation with deep veins thrombosis （DVT） or pulmonary embolism etc^[1].

　　The stress responses following surgical trauma are one of the most important factors to mediate perioperative coagulation / fibrinolytic disorders，and hypercoagulable state is its consequences^[2]. The clinical outcome is probably related to the potency of surgical stimulus，operation site，pre－existed hypercoagulable profile，age and so on^[3，4]. Restraining surgical stress responses might be dedicated to relieving blood hypercoagulation and / or protecting fibrinoloytic function，and then preventing the occurrence of postoperative thromboemblic events.

　　Different anesthesia techniques might have their unique impacts on perioperative stress response，and it was much concerned by anesthesiologists^[4～7]. The available clinical researches about the effects of anesthesia regimens on perioperative stress and coagulation / fibrinolysis are limited. Our study was based on the hypothesis，that diversity of anesthesia modes might affect the extent of stress responses，and the over－stressed responses most probably led to coagulation and / fibrinolysis imbalance and the occurrence of thromboembolic events. Our purpose is to observe the impacts of three conventional anesthesia methods （continued epidural anesthesia，epidural anesthesia combined general anesthesia and general anesthesia） on stress hormones （e. g.，catecholamine：epinephrine and nonepinephrine），coagulation parameters （platelets：Plt，prothrombin time：PT，partial prothrombin time：APTT，fibrinogen：FIB and thrombin－anti－thrombin Ⅲcomplex：TAT） and fibrinolytic parameters （D－dimer：DD，tissue－type plasminogen activator：t－PA and plasminogen activating inhibitor－1：PAI－1） during abdominal hysterectomy，and to seek the correlation of anesthesia methods with sur－gical stress，coagulation and fibrinolysis. We hereby wantto provide reasons for the choice of anesthesia techniques in the light of coagulation and / fibrinolysis in lower－ab－dominal surgery.

　　1 　Material and Methods<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

　　This research project was approved by Peking University People’s Hospital Ethic Committee，and sponsoredby Peking University People’s Hospital Research Grant .Each patient gave informed consent before entering intothis protocol .

　　1. 1 　Selection and grouping of patients

　　The thirty patients undergoing elective hysterectomy were randomLy selected with ages from 31 to 57 years，and ASA physical statuses Ⅰ～Ⅲ. There did not co－exist hypertension，coronary artery disease，diabetes mellitus，surgical history，renal or hepatic dysfunctions. Exclusive criteria included patients with anemia，coagulopathy，current anti－coagulation or anti－fibrinolytic medica－tion，non－steroid anti－inflammatory drugs （NSAID） and hormones history.

　　All patients were randomized into three groups：Continued Epidural Anesthesia （Group E，n＝10），Continued Epidural Anesthesia combined General Anesthesia （Group G+E，n＝10），and General Anesthesia （Group G，n＝10）.

　　1. 2 　Experimental procedures

　　1. 2. 1 　Pre－anesthesia preparation

　　Following the entry of patients into operation room，two ipsilateral arm veins were accessed，and then midazolam was given （0.05 mg/ kg，i. v） for sedation. For patients with general anesthesia，scopolamine （0.3 mg，i. v） was injected intravenously. Then，blood samples were taken from contralateral elbow vein for the measurement of stress hormones and coagulation / fibrinolysis parameters，and defined as baseline （T₀）. Anesthesia methods were detailed as follows. Group E：Epidural approach was made in lumbar 1～2（L_1～2） and cephalic catheterizing 3.5～4.0cm. Trial dosage （2％lidocaine 4～5 mL） was injected via catheter，and 0. 75 ％ bupivacaine （8～10 mL） was added 5 minutes after. Blocking level was tested with pinprick （from upper to lower） 20 minutes following the injection of initial local anesthetics，and injected－local anesthetic dose regulated to maintain blocking dermatome between T₆～L₃. 0.75 ％ bupivacaine injection （8～10 mL） was repeated per 50～60 minutes via epidural catheter throughout the operation. Group G + E：Epidural anesthesia method was detailed as above. General anesthesia induction was prolonged until the designed blocking level had been worked out during awaking. Anesthesia induction was carried out intravenously with propofol （1. 5～2. 0 mg/ kg），vecuronium （0. 1～0. 12 mg/ kg） and fentanyl （2～3 μg/ kg），and one－lumen intra－tracheal tube was orally inserted （OD：7. 5～8. 0 mm）. Anesthesia maintenance was managed with isoflurane in oxygen （FET：0.6％～0.8％），intermittent bolus of vecuronium （i. v.，2 mg） and repeated local anesthetic injection via epidural catheter. Mechanical ventilation and isoflurane inhalation were finished with Drager anesthesia machine （Drager IIB，U. S.A）. Respiratory variables were set out as tidal volume （VT） 8～10 mL/ kg and frequency 10～12 per minute （fresh oxygen flow 2 L/ min）. For all patients with general anesthesia，inspired fraction of oxygen （FiO₂） 100％ was supplied. The ventilation parameters were regulated to keep end－tidal partial pressure of carbon dioxide （P_ETCO₂） between 35～40 mm Hg. Group G：General anesthesia method was the same as described inGroup G + E，and anesthesia was maintained with isoflu－rane （F_ET：1.5％～2.0％） in oxygen.

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