The Effects Of Flurbiprofen Axetil On Platelet Aggregation For Perioperative Preemptive Analgesia In Laparoscopic Cholecystectomy

Pain was a special type of feeling of the body caused by noxious stimulation, causing a series of stress responses including that the catecholamines, epinephrine, norepinephrine, and cyclic adenosine monophosphate increased, the insulin sensitivity reduced and the glucagon secretion increased, which would change the metabolwasm, immune and organ function of the patients. Postoperative pain,as an acute noxious stimulus, would cause many adverse reactions, such as nausea, vomiting, muscle cramps, and severely damaged the physical and mental health of patients, furthermore affected the patient’s postoperative recovery. According to statwastics, more than half of postoperative patients underwent moderate pain and above. Except for the reasons such as surgical factors and patient illness, postoperative pain and the stress response were the causes of postoperative complications, and therefore a positive and effective treatment of postoperative pain may reduce the adverse reactions of the body, improve immune function, and reduce the occurrence of perioperative cardiovascular complications to promote the rehabilitation of the body.For perioperative pain, especially postoperative pain, the usual practice was to give pain medications immediately after surgery, but the effect was not always so efficient. Along with the accumulation of clinical experience and study of the molecular mechanism of pain,the concept of preemptive analgesia was proposed and applied to clinical work.The general preemptive analgesia refer to making measures before pain sensitivity in the spinal cord, to prevent the peripheral injury impulse delivered to the central, to reduced the threshold value of central sensitization, and it was not limited to administration time, including sustained suppression of incoming noxious stimuli and inflammatory responses during preoperative, intraoperative and postoperative, making the noxious stimulus fall below the threshold. There were a lot of drugs for preemptive analgesia and the non-steroidal anti-inflammatory drugs was one of them.It was at least3,500years since that NSAIDs applied for analgesic and antipyretic, and so far there were still millions of patients in the world using them every day. At the same time the adverse effects of NSAIDs limited their wider application. Anti-platelet aggregation which caused increased risk of bleeding was a very important aspect affecting the clinical application of NSAIDs, inducing blood loss and wound bleeding or other adverse reactions,which not only affected the clinical efficiency of NSAIDs, but also even endanger the safety of patients. So the impact of NSAIDs on coagulation has been the focus of attention of clinicians. Flurbiprofen was with well performance and less adverse reactions in the non-steroidal anti-inflammatory drugs,which has a good analgesic effect in the minor surgery, and was verificated by medical evidence that its preemptive analgesia effect were good and with less postoperative adverse reactions such as nausea and vomiting. Flurbiprofen axetil were non-selective COX inhibitors, which could reduce the formation of TXA2, may affect platelet activation and aggregation, furthermore may also lead to postoperative bleeding and other adverse reactions.Flurbiprofen axetil were commonly used in preemptive analgesia with clinical dose of100mg and50mg,and many studies had shown that both had good analgesic effect, but the comparation of analgesic effect between the two doses and their effects on platelet aggregation were few reported. Arachidonic acid generated prostaglandin G2and H2(PGG2and PGH2) by the cyclooxygenase (COX), then generated thromboxane A2(TXA2) catalyzed by platelet thromboxane synthetase.The TXA2can reduced platelet intracellular cAMP concentration, which had positive feedback function to promote platelet aggregation. Arachidonic acid were commonly used as the inducer in platelet aggregation test. This study used arachidonic acid as inducer, and used platelet aggregation analyzer to measure the effect of different doses of flurbiprofen axetil on platelet aggregation, at the mean time to compare the analgesic effect of different doses of flurbiprofen axetil, and to observe intraoperative and postoperative bleed loss and postoperative complications, to determine its perioperative balanced analgesia safety, and to look forward to help the clinical work.Method:30patients undergoing elective laparoscopic cholecystectomy surgery,aged from18to45years old,body mass index:20-25kg/m2, ASA:I-11-class,and all patients met the inclusion criteria. There were no loss to follow or test interruption cases.Before anesthesia all patients intramuscular injection of diazepam10mg and atropine0.5mg.The vein pathway was opened up in the operating room by nurse. Monitor blood pressure(BP), mean arterial blood pressure (MAP), heart rate(HR), pulse oxygen saturation(SpO2) and partial pressure of end-tidal carbon dioxide(PetCO2).TCI of propofol and remifentanil and sufentanil0.25ug·kg-1were used to induce anesthsia. And neuromuscular block was achieve with rocuronium0.9mg·kg-1, followed by tracheal intubation. Total intravenous anesthesia of propofol and remifentanil was used to maintain the depth of anesthesia, and appended rocuronium if needed. After the surgery and extubation the patients were sent to ward when they were awake.All the patients were randomly divided into three groups (group C, preemptive analgesia Group F1, preemptive analgesia group F2).10minutes before surgery,group C received Intravenous injection of10ml saline. Group F1received intravenous injection of flurbiprofen axetil50mg,and group F2received intravenous injection of flurbiprofen axetil100mg. The intravenous process was lasting more than one minute. After induction,chose three time:after the test drug but before the surgery(T1), immediately after the surgery (T2), and6h after the surgery (T3).Took anticoagulated venous blood2ml,and tested its platelet aggregation within2hours. Record intraoperative blood loss, pain vasual analogue scale(VAS) of2h,6h,24h after the operation, postoperative nausea, vomiting, dizziness and other adverse reactions. All statwastical analyzes were completed using SPSS13.O statwastical softwwere or Excel. P<0.05were accepted as statwastically significant.We also comprehensively evaluated the effect of flurbiprofen axetil preemptive analgesia for laparoscopic cholecystectomy with Meta-analysis.Results1、There were no statistical significance of three groups of patients between the age,weight,gender,height and ASA physical status(P>0.05).2、There were no significant differances in induction time of anesthesia, operation time,volume of intraoperative fluid and blood loss, intraoperative urine output (P>0.05).3、VAS score:difference was statistically significant beween group C and group F1at6h, from an average of4.9points down to3.9points, and at24h from an average of5.8points down to3.2points,; difference was statistically significant between group C and group F2at6h from an average of4.9points down to3.8points,24h from an average of5.8points down to2.7points; differences in scores were not statistically significant beween F1group and group F2(P>0.05).4、Adverse reactions incidence:the difference was not statistically significant beween the groups (P>0.05).5、Platelet aggregation function:comparison at each time has statistical significance (P<0.05), in group C T2compared to T1has increased1.7average Ω, F2group T3compared to T2has increased by an average of3.1Ω. Comparison between groups was statistically significant difference (P<0.05):compared to T2in group C,T2in F1group has increased an average of2.3Ω, T2in F2group3.1Ω. The other points have no statistically significant difference (P>0.05).6、The meta-analysis showes that flurbiprofen axetil preemptive analgesia for laparoscopic cholecystectomy has a better effect without increasing the incidence of adverse reactions.Conclusions1、Flurbiprofen axetil for preemptive analgesia can improve the efficiency of postoperative analgesia.2、Preoperative intravenous injection of flurbiprofen axetil50mg for perioperative preemptive analgesia was safe, effective, feasible, and no obvious effect on platelet aggregation function; it can be safely used in the perioperative period;3、Preoperative intravenous injection of100mg of flurbiprofen had a significant effect on platelet aggregation function immediately after the operation; but had no obvious effect on platelet aggregation6h after the opration; had no significant effect on intraoperative and postoperative blood loss.