Discussion on the use of dizocine in the perioperative setting

ZHANG,Zhe1,LIU,Yang1,LIU,Ailing1,GAO,Song2,MA,Li3

1.Department of Anesthesiology,32295 Troops,Liaoyang Liaoning 111000,China

2.Department of medical imaging,32295 Troops,Liaoyang Liaoning 111000,China

3.Army cadre ward,32295 Troops,Liaoyang Liaoning 111000,China

【Abstract】Summary to explore the use of dezocine in the perioperative period.

【Key words】Dizocine;Perioperative;Application

Dizocine as a novel opioid receptor agonist antagonist, fully agonistic κ Receptor, partial agonism μ Receptors, does not produce typical μ Receptor dependence, on δ Receptors also have some agonism. Because of its strong analgesic effect, poor dependence, and little side reactions, its application in the perioperative period has been paid more and more attention, and is now reviewed below.

1 Mechanism of action and pharmacokinetics of dezocine

Dizocine is a potent opioid with analgesic strength, onset, and duration of action comparable to morphine. Postoperative pain is relieved when the steady-state blood concentration exceeds 5-9 ng / ml, but adverse effects occur when the average peak concentration reaches 45 ng / ml; It can be absorbed quickly and completely after the injection, with a peak time of 10-90 min at 10 mg intramuscularly and a mean plasma concentration of 19 ng / ml (range 10-38 ng / ml). 10mg intravenously over 5min resulted in a mean terminal half-life of 2.4h (1.2-7.4h), a mean volume of distribution of 10.1l/kg (4.7-20.1l / kg) and a mean systemic clearance of 3.3l/hr/kg (1.7-7.2l / HR / kg).

2 Dizocine in general anesthesia

2.1 induction period

The use of dizocine in the induction phase of general anesthesia can inhibit the pharyngeal and cardiovascular reflexes caused by tracheal intubation and other adverse stress reactions [1], maintain circulatory stability and prevent fentanyl and sufentanil induced choking reactions [2-3], and the specific mechanism may be associated with the following factors [4-6]. ① dizocine acts on the C receptor of the bronchi to exert a constrictive effect on tracheal smooth muscle against sunitinib and ② Reduce the release of histamine to suppress choking reactions; ③ Competitively prevents sufentanil binding to opioid receptors; ④ Effects produced by agonistic K receptors that inhibit fentanyl action on μ Agonistic effect of receptor, suppress choking reaction. Chiang guijoan et al [7] showed that while intubated in general anesthesia, intravenous dizocine (0.2 mg / kg) was more effective than intravenous fentanyl (3 μ G / kg), which is more effective in suppressing the stress response to tracheal intubation under general anesthesia and maintaining a stable circulatory condition, which may be associated with dezocine agitation μ Receptors, antagonism κ Receptors, and inhibits PNE and serotonin reabsorption, reducing sympathetic adrenergic system reflexes are involved [8]. Studies by Li Guoli [9] showed that 0.2 mg / kg dizocine for amnesic analgesia slowly induced anaesthesia inhibited the stress response of tracheal intubation better than 2 μ G / kg fentanyl) with appropriate sedation scores and a low incidence of adverse effects.

2.2 Extubation period

Dizocine can obviously reduce the cardiovascular malignant reaction and agitation in the awakening period during extubation from general anesthesia. Yu Hong [10] and others intravenously injected different doses of dizocine 30 minutes before the end of laparoscopic gallbladder surgery, the results suggested that intravenous 0.1 mg / kg dizocine could exert maximum analgesic effect before the disappearance of remifentanil's analgesic effect after discontinuation of general anesthetics, while avoiding stress reaction produced by painful stimulus after the end of surgery and reducing the incidence of adverse reactions during the awakening period of general anesthesia without affecting respiratory and circulatory indexes. Ametrine butan [11] and other studies confirmed that the use of 0.07 mg / kg dizocine preemptively before induction of general anesthesia can significantly reduce the occurrence of postoperative agitation, and can reduce postoperative BP and HR and other cardiovascular effects, while it can significantly relieve postoperative pain and obviously reduce postoperative adverse effects in patients. In addition, different modes of administration also affect the role of dezocine on postoperative adverse effects of general anesthesia. Shao Tao [12] used patients undergoing laparoscopic gallbladder surgery under remifentanil compound anesthesia to administer dezocine 0.2 mg / kg intramuscularly or intravenously 30 min before the end of the surgery, and found that dizocine intramuscularly 30 min before the end of the surgery, effectively attenuated hyperalgesia, shortened the time to awakening and extubation, improved postoperative analgesia and sedation, and had a good safety profile. In pediatrics, Yanjun Zhang [13] and others observed that preoperative intravenous bolus of 0.05mg/kg and 0.1mg/kg dizocine groups were both effective in reducing pediatric sevoflurane compound anesthesia awakening agitation, but intravenous bolus of 0.05mg/kg dizocine was effective in reducing pediatric sevoflurane compound anesthesia awakening agitation with appropriate sedation intensity and did not prolong postoperative stay.

3 Use of neuraxial anesthesia

Neuraxial anesthesia patients in a state of wakefulness, the discomfort of anesthesia itself, the intraoperative traction reaction and the patient's fear of surgery, etc., lead to patient tension anxiety, even a sensation of frequent death, very unfavorable to the smooth progress of surgery, therefore adjuvant medication is essential, dizocine as a new type of opioid receptor agonist antagonist has also been continuously tried in the clinic, studies have shown [14] intravenous dizocine 5 mg, It could decrease the BIS value after 10 min (BIS 90.2 ± 3.1, P < 0.05) and had a sedative effect, which might follow the excitation of the central κ Receptors involved. Dizocine 5 mg compounded with midazolam 2 mg, resulted in decreased BIS values after 10 min (BIS 73.1 ± 2.9, P < 0.05), 100% anterograde amnesia without significant respiratory depression, was safe and comfortable, and was suitable for sedation and analgesia in perioperative patients. However, because midazolam has a short half-life and a short duration of action, we found in this study that patients wake up about 30 min after a single injection with BIS > 90 and that intermittent administration can make the patients sleep back, but the blood concentration fluctuates greatly, the hemodynamic effects are large, and it cannot completely ensure the elimination of the patients' adverse intraoperative memory, therefore, a single injection of dizocine combined with midazolam might be a more ideal method. Jing Hui Chen [15] and other studies found that: the single drug use dose of dizocine should be as less than 0.2 mg / kg as possible, and the inhibitory effect of this dose on the respiratory function of the patient is relatively weak, and does not affect the plane of anaesthesia, thereby enabling the expected effects of anaesthesia to be achieved.

4 Use in nerve blocks

Nerve block has been widely used in surgeries where the lesions on the extremities or body surface are limited because of its unique features, such as small block size, minimal interference with the organism, and convenience in perioperative management, but it is also because of this characteristic that incomplete block often occurs intraoperatively and that dizocine can strengthen its anesthetic effect.16 Shen Bao Qu é [16] found that brachial plexus block with the addition of a small amount of dizocine to a local anesthetic markedly accelerated the onset of anesthesia, Prolonging the block time and improving the success rate of anaesthesia. 5,6 in addition, Wang Fu Xiang [17] and others made a clinical observation on the different modes of administration of dizocine found that the administration mode of dizocine regional adjuvant anaesthesia was better than that of intravenous adjuvant applied to nerve block anaesthesia, which may be related to its opioid receptors acting on the peripheral system

5 Use in day surgery

In recent years, daytime surgical anaesthesia has mostly been accomplished with CO administered opioids (fentanyl or sufentanil, etc.) such as propofol or sevoflurane, but intraoperative side effects such as respiratory depression, nausea and vomiting are easily observed. Currently, it is considered that low-dose intravenous dezocine 0.1-0.15mg/kg combined with propofol or sevoflurane can be safely and effectively applied in day surgery such as painless enteroscopy, ureteroscopy, hysteroscopy, electronic fiber bronchoscope and human flow surgery, which significantly reduces the cardiovascular reaction caused by operation, analgesia and sedation is complete and awakening is rapid.

6 Postoperative analgesia

Dizocine can be used alone for postoperative analgesia.18 Gao Guang Wu et Al18 administered dizocine 0.1 mg / kg or sufentanil 1 intravenously to patients after surgery for thyroid cancer, respectively μ G / kg) was administered for analgesia the results suggested that there was no significant difference in VAS scores at each time point within 12 hours after surgery between the two groups. However, the incidence of adverse effects in the dezocine group was 26.67% (P > 0.05), The difference was 91.11% in sufentanil group (P < 0.05). This is consistent with the findings of Xiaozhen Zheng et al.19 in their study on postoperative analgesia with dizocine in elderly orthopedic surgery patients and Yin Liu et al.20 in their study on postoperative intravenous analgesia with dizocine in pediatric otorhinolaryngology patients. 21,22 the same Study21 separately compared 0.80 mg / kg dizocine with 0.01 mg / kg fentanyl in patients with gynecological malignancies and found that the, Its analgesic effect and suppression of postoperative stress response were superior to those of the fentanyl group; And to some extent, they protect the organism's survival function, suggesting that compared with fentanyl, dizocine is more suitable for postoperative analgesia in patients with gynecologic malignancies.22 in addition, Li Sheng liu22 showed that compared with fentanyl, dizocine analgesia has little effect on cognitive function and rapid postoperative recovery in elderly patients, which may be due to the fact that dizocine has no secondary distribution effect of fentanyl, and its drug elimination half-life is shorter than that of fentanyl, Accelerated the metabolism of drugs in the body, resulting in improved postoperative cognitive function.

Dizocine can be combined with opioids, NSAIDs, intravenous injections such as dexmedetomidine or postoperative intravenous controlled analgesia can reduce pure μ The dose of receptor opioid agonists, which reduce the occurrence of side reactions such as dizziness, somnolence, nausea, and vomiting, strengthen the sedative effect, strengthen the analgesic effect of NSAIDs, and effectively inhibit postoperative chills.23-25 they can also be used in combination with dexamethasone and ropivacaine for postoperative self-controlled analgesia with local infiltration, epidural, or nerve block. Yingmei Zheng et al23 found that dexamethasone combined with dizocine could obviously shorten the onset time of intermuscular groove nerve block, prolong the duration of analgesia and obviously reduce the adverse effects such as nausea and vomiting.24 however, Wang Xu et al24 found that a compound small dose of dizocine was insufficient to compensate for the disadvantage of a shorter duration of analgesia caused by a low concentration of ropivacaine. Bingyanqiu et al [25] showed that the exact epidural analgesic effect of 5 mg dezocine compounded with 0.2% ropivacaine and 100 ml normal saline was not statistically different from that of morphine (P > 0.05), but the adverse effect was significantly less (56.7% in morphine group vs 6.7% in dizocine group

In summary, dizocine can be used alone or in combination with other drugs at all stages of the perioperative period, and the analgesic effect is exact and has a certain sedative effect with few adverse effects, which is suitable for clinical promotion and application, but the dosage, mode of administration, and drug compatibility at each stage need further refinement research, and in addition, relative to special populations (such as advanced age, infants, and those with hepatic and renal dysfunction) still needs further study.

Reference

[1]Guo Yanru,Shan Shiqiang.Comparison of clinical effects of diazosine and fentanyl on inhibition of tracheal intubation stress response[J].China Comprehensive Clinical Journal,2011,27(10):1044-1046.

[2]Huang Meihua,Wang Hui,Xu Jin,etc.Comparison of the effect of oxycodone and diazosine in preventing cough response induced by fentanyl during anesthesia induction[J].Chinese Journal of Anesthesiology,2015,35(7):787-789.

[3]Zeng Qingling,Tang Peijia,Xu Yuexiu,etc.The preventive effect of diazosin on the cough response induced by sufentanil during induction of general anesthesia[J]Chinese Medicine,2015,10(2):223-226.

[4]xu B，Wang ZP，Wang YJ，et a1．The toxic effect of opioid analgesics on human sperm motility in vitro[J]．Drug Chem Toxicol，2013，36(2)：205-208．

[5]Song Bin,Li Chen,Shi Yongzhou,et al.Application of Dizosin in early analgesia of chest trauma[J].Chinese Medical Journal,2013,8(10):1430-1432.

[6]Lu Y，Ye Z，Wong GT，el a1．Prevention of injection pain due to propofol by dezocine：a comparison with lidocaine[J]．Indian J Pharmacol，2013，45(6)：619-621．

[7]Jiang Guiqiong,Tan Shanshan,Zhu Shanshan.Effect of Dezosin on plasma epinephrine and norepinephrine in patients during general anesthesia intubation[J]Guangdong Medical Journal,2015,36(21):3290-3292.

[8]MANNE G R，UPADHYAY M R，SWADIA V，et a1．Effects of low dose dexmedetomidine infusion on haemodynamic stress response，sedation and post—operative analgesia requirement in patients

undergoing laparoscopic cholecystectomy[J]．Indian J Anaesth，2014，58(6)：726—731．

[9]Li Guoli,Wang Rong,Liu Wei,etc.Study on the effect of diazosin and fentanyl on the stress response to tracheal intubation in amnesia analgesia slow induction anesthesia[J]Chongqing Medical Journal,2015,44(13):1796-1798.

[10]Yu Xianghong,Huang Sheng,Xiao Jianpeng Comparison of different doses of diazosin in reducing cardiovascular response during extubation under general anesthesia[J].Journal of Clinical Anesthesiology,2013,29(3):251-253.

[11]Ding Cuiqing,Liu Zhiyong Analysis of the effect of Dizosin on postoperative restlessness in patients undergoing remifentanil combined with general anesthesia[J]Chongqing Medical Journal,2016,45(2):680-682.

[12]Shao Tao,Hu Haiyan.The effect of different administration methods of diazosin on extubation and analgesia and sedation after remifentanil combined anesthesia in the recovery period[J]Practical Medicine and Clinical,2014,17(8):996-1000.

[13]Zhang Yanjun,Li Rong,Liu Jinzhu.Effect of different doses of diazosine on restlessness in children during recovery from sevoflurane combined anesthesia[J]Chongqing Medical Journal,2016,45(1):74-80.

[14]Du Shunyan,Liang Xiaoxia,Hu Xudong Effect of diazosin combined with midazolam or droperidol on bispectral index of EEG in patients with combined spinal-epidural anesthesia[J]Guangdong Medical Journal,2016,37:207-209.

[15]Chen Jinghui,Li Guoli Effects of two doses of diazosine on respiratory function and depth of anesthesia in patients undergoing lower limb surgery[J]Journal of Clinical and Experimental Medicine,2016,15(11):1119-1122.

[16]Shen Baokui,Dezosin combined with levobupivacaine for brachial plexus block anesthesia effect analysis[J].North Pharmaceutical 2017,14(5):57.

[17]Wang Fuchao,Zhao Hairui,Chen Jinhui,et al.Comparison of analgesic effects of different administration methods of diazosin in combined lumbar plexus and sciatic nerve block[J]Guangdong Medicine 2017,38(18):2862-2864.

[18]Gao Guangwu,Zhu Jie,Zhang Jie.Observation on the effect of diazosine on postoperative analgesia in patients with thyroid cancer[J].China Practical Medicine,2016,11(8):165-166.

[19]Zheng Xiaozhen,Hong Daoxian,Han Xiaodi.Clinical study of Dizosin for postoperative patient-controlled intravenous analgesia in elderly patients[J]Journal of Clinical Anesthesiology 2012,28(5):460-462.

[20]Liu Zhen,Wang Meng.Clinical observation of Dizosin for postoperative intravenous analgesia in pediatric otorhinolaryngology[J].Journal of Practical Medicine,2015,32(8):721-722.

[21]Gu Xiaolan,Li Pengyi,Gu Lianbing.Effect of postoperative analgesia with diazosine on plasma catecholamine and immune function in patients with gynecological malignancies[J]Journal of Clinical Anesthesia,2015,31,(9):837-841.

[22]Liu Lisheng,Qian Weimin,Dong Wenfang,et al.The effect of intravenous analgesia with diazosine and fentanyl on postoperative cognitive function of elderly patients[J].China Contemporary Medicine,2015,22(20):102-108.

[23]Zheng Yingmei,Chen Dong,Ding Yanqun.The effect of dexamethasone 10mg combined with diazosine on intermuscular groove brachial plexus block[J]Journal of Clinical Anesthesiology,2013,29(12):1190-1192.

[24]Wang Xu,Gao Yuhua,Guo Bin,et al.The application of continuous femoral nerve block of ropivacaine combined with sufentanil or diazosin in postoperative analgesia after total knee arthroplasty[J]Journal of Clinical Anesthesiology,2016,32(3):258-261.

[25]Bing Yanqiu,Chen Bingyu,and comparison of the effects of Dizosin on postoperative epidural analgesia[J].China Medical Innovation,2015,12(4)(total 322):147-148.