Different Doses Of Nalmefene In The Application Of Laparoscopic Gynecologic Perioperative Analgesia

Objective:To study the effects of different doses of nalmefene in the inhibition of remifentanil hyperalgesia response after surgical operation and adverse reactions by use before induction of gynecological laparoscopic operation, and to explore the optimal dose. Methods:100 patients were chosen from Yan An University affiliated hospital, who would schedule for gynecological laparoscopic operation, ASA I-II, from May 2015 to Mar 2016. The operation consist of panhysterectomy, resection of the uterus and fallopian tube hysterectomy and adnexectomy, age 31 to 55 years old, weight 50-77 kg, BMI 24.60±2.15kg/m2. Randomly divided into 5 groups, 20 patients in each group. Group A(control group, normal saline 5ml), Group B(nalmefene 0.1ug/kg, diluted with saline for a total capacity of 5ml), Group C(nalmefene 0.2ug/kg, diluted with saline for a total capacity of 5ml), Group D(nalmefene 0.3ug/kg, diluted with saline for a total capacity of 5ml), Group E(nalmefene 0.4ug/kg, diluted with saline for a total capacity of 5ml).the drug mentioned above were respectively slow injectived(injection time more than 30 seconds), 5min before the induction of anesthesia,then all patients received routine anesthesia induction:midazolam 0.05mg/kg, fentany l4ug/kg, propofol 1mg/kg, cisatracurium besylate 0.15mg/kg. Intraoperative continuous infusion propofol, remifentanil by micro pump to maintain stable anesthesia, interrupted administration of cisatracurium besylate to maintain muscle relaxation. All patients using the same postoperative analgesia pump formula:fentanyl 14ug/(kg·50h), tropisetron 10 mg, plus saline to 100 ml(The first dose 3ml, maintenance dose 2ml/h, single dose 2ml, locking time15min), connect the PCIA 20 min before surgery and give the first dose. Observed indicator:(1) Observed and recorded the SBP NBP HR for entering the operation room(T0), 5 min after given experimental drug(T1), intubation(T2), 5 min after intubation(T3), 5 min before extubation(T4), extubation(T5), 5 min after extubation(T6) and observe the change of ECG in surgical procedures;(2) Observe postoperative respiratory recovery time and extubation time;(3) The total amount of remifentanil and propofol intraoperatively;(4) Recorded the VAS values score 1h, 2h, 24 h, 48 h after the surgery,(5) The PCIA total pressing number and valid pressing times at 24 h and 48 h after the surgery;(6) Observe postoperative nausea, vomiting, drowsiness and other adverse reactions and the first flatus time. Result:1. Five groups of patients hemodynamic fluctuation between intubation and entering the operation room showed no significant differents(P>0.05), during Intubation(T4, T5, T6), the SBP, NBP, HR of group C,D were lower than group A, the difference has statistical significance(P<0.05). The SBP, NBP, HR of group C were lower than group D, the difference was significant differents(P>0.05). Group comparison:C,D group decreased in extubation at SBP compared with T0(P<0.05), C group decreased more(P<0.01); A, B group increased in T5 at HR compared with T0(P<0.01); E group increased in T5 at SBP, NBP, HR compared with T0(P<0.05).2. Five groups of patients in postoperative respiratory recovery time C, D, E group were shorter than A, B group, the difference was clear statistically significant(P<0.01), the postoperative respiratory recovery time of E group was the shortest,but there was no significant differents compared with C,D group(P>0.05); Extubation time B, C, D, E group is shorter than A group(P<0.01), C, D, E group is shorter than B group(P<0.01), the extubation time of E group was the shortest, but there was no significant differents compared with C,D group(P>0.05).3. There were significant differents between five groups of patient′s the total amount of remifentanil(P<0.01),the total amount of remifentanil:B, C, D, E group were less than A group(P<0.01), C group was less than B, E group(P<0.01), C group was the least, but there was no significant differents compared with D group(1014.75±101.22 ug vs. 1090.00±118.81 ug,P=0.05); there were significant differents for five groups of patient′s the total amount of propofol(P<0.05), the total amount of propofol: B, C, D group were less than A group was statistically significant(P<0.05), B group was the least, but there was no significant differents compared with C,D group(P>0.05); E group matched with A group, there was no significant differents(P=0.189).4. Five groups of patients′ VAS values score 2h after the surgery, A group was higher than B, C, D, E group, the difference was clear statistically significant(P<0.01),and C group is lower than B group(P=0.03), D group is lower than E group(P=0.014); The VAS values score 24 h after the surgery, A group was higher than B, C, D group, the difference has clear statistically significant(P<0.01),and C group was lower than B, D, E group, the difference was statistically significant(P<0.05); Group comparison: A group raised in 2h after the surgery at VAS values score compared with 1h after the surgery,the difference was clear statistically significant(P<0.01), B, C, D, E group raised in 2h after the surgery at VAS values score compared with 1h after the surgery,the difference was statistically significant(P<0.05), C group raised little in 2h after the surgery at VAS values score compared with 1h after the surgery,the difference was no statistically significant(P>0.05).5. Five groups of patients′ the PCIA total pressing number and valid pressing times, all patients′ pressing number were valid, B, C group compared with A group the PCIA total pressing number were decreased at 24 h, 48 h after the surgery(P<0.01) and C group is the least, compared with A, B, D, E group the difference was clear statistically significant(P<0.01); E group compared with B group the PCIA total pressing number were increased at 24 h after the surgery, the difference was statistically significant(P=0.033); D group the PCIA total pressing number was decreased than A group at 48 h after the surgery(P<0.01), E group the PCIA total pressing number was increased than A group at 48 h after the surgery the difference was statistically significant(P=0.002).6. Five groups of patients′ postoperative nausea,vomiting degree,D group was the least(P<0.01),mean rank was 37.50, 39.35; drowsiness decreased with the increasing dose of nalmefene, but this trend is mainly in the A group and the B group,there were no change after C group,it showed that the rate of drowsiness is lower in C group; compared with A,B group the first flatus time was shorter in D,E group(P<0.01). Conclusions:1. Low doses of nalmefene can inhibit postoperative pain hypersensitivity of remifentanil and reduce the dosage of remifentanil during operation,and reduce nausea, vomiting and other adverse reactions.2. Advanced use of 0.2ug/kg nalmefene can better inhibit postoperative pain hypersensitivity of remifentanil reduce the dosage of remifentanil during operation, and reduce nausea, vomiting and other adverse reactions.