Cheng-Yun Hu,Lai Jiang,Zhe-Tao Zhang,Chao-Liang Tang

1Department of Anesthesiology,Anhui Provincial Hospital,Wannan Medical College,Hefei 230001,China.2Department of Obstetrics and Gynecology,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei230001,China.3Department of Pharmacy,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230036,China.4Department of Anesthesiology,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001,China.

Abstract Anesthesia is mainly a kind of reversible functional inhibition of the central nervous system and(or)peripheral nervous system through drugs or other methods.In modern clinical medicine,modern anesthesiology is a comprehensive subject,which mainly includes clinical anesthesia,pain diagnosis and treatment,intensive care treatment,first aid and resuscitation,etc.Electroacupuncture is developed based on acupuncture therapy which is an important part of traditional Chinese medicine.It uses the comprehensive efficacy of acupuncture and electrical stimulation to deliver electrical energy through acupoints to achieve therapeutic effects.It has been widely used in recent years in clinical.This article summarizes the analgesic mechanism of electroacupuncture and its application in different anesthesia methods,so that clinicians have a deeper understanding of the clinical application of electroacupuncture and promote its clinical application.

Keywords:Electroacupuncture,Anesthesia,Analgesia,Cognitive dysfunction,Perioperative period

Background

Clinical anesthesiology has shown great changes in terms of the anesthetic drugs,anesthesia equipment and anesthesia concepts and methods in a history of more than 150 years.However,various anesthesia methods have some shortcomings.For example,general anesthesia requires multiple medications or combined with multiple anesthesia techniques,which has the disadvantages of large and complex medication and strong stress response when extubating.Combined spinal-epidural anesthesia has the higher incidence of headache,not only brings pain to the patient,but also increases the patient’s body stress response,affects postoperative wound healing,and prolongs the postoperative recovery time.In recent years,enhanced recovery after surgery has been promoted,which requires us to further optimize the anesthesia method during the perioperative period to provide patients with comfortable medical treatment.

Acupuncture therapy has a history of more than 2,500 years in China[1].With the development of science and technology,acupuncture technology is constantly evolving,from the initial hand-twisted acupuncture to the current electric acupuncture and transcutaneous electrical acupoint stimulation.Originated in 1958,acupuncture anesthesia is based on different types of operations and surgical sites,according to the principles of meridian,syndrome differentiation,local or symptomatic acupoint selection[2].It is a method of anesthesia for surgical operations after which the patient remains awake but reaching a certain anesthetic effect.Acupuncture anesthesia needs to be operated at specific acupoints and is time-consuming,so it is difficult to popularize in today’s operating rooms.With the same theoretical basis,using electric current instead of acupuncture,electroacupuncture can achieve the effect of standard acupuncture in a short time[3].Electroacupuncture can be used as an effective means of auxiliary anesthesia in the perioperative period and has shown many benefits such as relieving anxiety and preemptive analgesia before surgery;reducing the use of anesthetics during surgery;effectively reducing the incidence of postoperative nausea vomiting(PONV)after surgery,relief of postoperative pain,prevention of postoperative stress and postoperative cognitive dysfunction(POCD).The use of electroacupuncture is relatively simple and easy and can provide a stable and effective acupuncture effect without a professional acupuncturist,which provides the feasibility and practicability for the application of electroacupuncture in clinical anesthesia.

The analgesic mechanism of electroacupuncture

Pain,listed as the“fifth vital sign”in 1995,is the subjective feeling of the patient,the unpleasant feeling and emotional experience caused by tissue damage or potential tissue damage[4].It not only brings physical and mental effects to the patient,but may also cause pathological changes in the nervous,circulatory,and endocrine systems,affecting the quality of life of the patient.In our country,electroacupuncture has been widely used in the treatment of various diseases and accepted by the public because of its remarkable analgesic effect[5],it activates a variety of biologically active substances through multiple signaling pathways around and on the spinal cord to produce analgesic effects[6].Electroacupuncture analgesia is produced by releasing endogenous opioid peptides or activating the endogenous pain suppression system[7].Different causes of pain also involve different signaling pathways and molecular levels.In inflammatory pain,electroacupuncture has the dual effects of analgesia and anti-inflammatory,cyclooxygenase 2 mainly regulates the release of inflammatory mediators,which can lead to the production of inflammatory pain,and vanilloid receptor plays an important role in neuropathic pain[8].Fang et al.found that electroacupuncture may act through the p38 mitogen activated protein kinase/activated transcription factor 2/vanilloid receptor 1 pathway that regulates the duration of inflammatory pain rather than regulating p38 mitogen activated protein kinase/activated transcription factor 2/cyclooxygenase 2 pathway[9].Researchers established a rat model of acute gouty arthritis and by using electroacupuncture,they found that through peripheralκandμopioid receptors,it upregulated the expression ofβ-endorphin in inflamed skin tissues and effectively relieved pain[10].In neuropathic pain,electroacupuncture can regulate neurotransmitters and related receptors,reduce hippocampal excitatory neurotransmitter glutamate content,and increase the content of inhibitory neurotransmitterγ-amino-butyric acid to reduce neuropathic pain in higher brain areas[11].In addition,electroacupuncture can also stimulate the expression of interleukin 10 in microglia,and inhibit neuropathic pain by interleukin 10 mediating the expression ofβ-endorphin in spinal microglia[12].

Electroacupuncture in perioperative anesthesia management

Electroacupuncture combined with local anesthesia

Local anesthesia is the application of local anesthetics to block the nerve conduction temporarily,completely and reversibly in a certain area of the body,so that this area has an anesthetic effect.Clinically,generalized local anesthesia includes surface anesthesia,local infiltration anesthesia,regional anesthesia,nerve block,and intraspinal anesthesia.Although local anesthesia can preserve the patient’s consciousness and maintain the protective reflex,its analgesic effect is often not ideal[13].The pain of the surgical operation may stimulate the body to cause violent fluctuations in circulation,and the traction on the peritoneum makes the patient feel uncomfortable.The need for multiple administrations during the operation has a certain impact on the quality of the operation and the recovery of the patient after the operation.In addition,even if the block level of intraspinal anesthesia is higher,it cannot completely eliminate the discomfort or nausea and vomiting caused by intra-abdominal operation,and it can easily cause postoperative chills,headaches,and urinary retention,which is not conducive to postoperative recovery which will reduce the quality of life[14,15].Modern medicine has confirmed that after electrical acupuncture stimulation,the brain releases neuroactive substances such as endorphins,serotonin,and other cytokines,which affect the transmission of pain signals and thereby produce analgesic effects[16].Xiao et al.conducted a study on the complications related to labor pain and anesthesia during labor analgesia with electroacupuncture,and found that electroacupuncture combined with combined spinal-epidural analgesia and patient-controlled epidural analgesia could reduce the visual analogue score of labor pain by 1 to 2 points,and reduce the incidence of urinary retention[17].After subarachnoid block(spinal anesthesia for short),due to the inhibition of the lumbosacral spinal cord and the dysfunction of the detrusor,the bladder is overfilled,and urinary retention is formed.Gao et al.showed that electroacupuncture combined with spinal anesthesia can reduce postoperative urinary retention and shorten the spontaneous urination time of patients[18].Shivering is also a common complication after regional anesthesia.The use of electroacupuncture at specific points can maintain the body’s core body temperature,thereby reducing the incidence of shivering after anesthesia[19],but this is closely related to the effective duration of electroacupuncture stimulation which needs to overcome technical difficulties[15].In total knee arthroplasty,electroacupuncture combined with continuous femoral nerve block can provide effective anesthesia,and can also relieve postoperative pain[20].Electroacupuncture combined with local anesthesia can increase the analgesic effect of anesthesia,which is superior to local anesthesia alone,and can reduce postoperative complications and benefit patients’postoperative functional recovery.

Electroacupuncture combined with general anesthesia

General anesthesia refers to the inhalational,intravenous or intramuscular injection of anesthetics into the body,resulting in temporary depression of the central nervous system throughout the body.With the development of medical technology,general anesthesia can be safely and effectively applied to surgical operations,but a series of adverse reactions such as reduced perioperative respiratory function,unstable hemodynamics,large dosage of anesthesia,and prolonged recovery time still often occur,the stress response generated by the operation can last for many days after surgery,affecting the treatment effect and postoperative recovery of patients[21-23].Animal experiments have confirmed that electro-acupuncture analgesia can be used in various animal operations and has the advantages of safety,less physiological interference,fewer complications,and quicker recovery after surgery although there are also unsatisfactory muscle relaxation and insufficient analgesia have also occurred during the operation[24,25].Jin et al.compared the anesthesia effects of simple general anesthesia and electroacupuncture combined with general anesthesia,and found that the perioperative blood pressure,heart rate,adrenocorticotrophic hormone,cortisol,epinephrine and blood sugar in the electroacupuncture combined group are more stable,and the cardiovascular stress response is also smaller[26].In an analysis evaluating the efficacy of electroacupuncture combined with general anesthesia in patients undergoing cardiac surgery,it was found that compared with the general anesthesia group,the vasoactive drugs required by the electroacupuncture combined with general anesthesia group were significantly reduced,and the intraoperative myocardial cell damage was significantly reduced.The need for intraoperative anesthetics is also reduced,which significantly shortens the time of mechanical ventilation and the time spent in the intensive care unit,and reduces the level of pro-inflammatory mediators[1].Electroacupuncture combined with general anesthesia has significant advantages,has a significant regulatory effect on the body’s circulatory function,can promote hemodynamic stability,and has a good application prospect.

Effect of electroacupuncture on perioperative anxiety

Preoperative anxiety is as high as 20%-80%of patients undergoing elective surgery[27,28].Traditional Chinese medicine believes that anxiety is mainly caused by the stasis of Qi,which leads to imbalance of Qi and blood in the viscera,dysfunction.Preoperative anxiety increases the sensitivity of the patient’s pain response,the demand for postoperative analgesics,prolongs the postoperative recovery time,and is detrimental to the patient’s postoperative recovery and physical and mental health[29].At present,the effects of drugs in the treatment of anxiety are average and have certain side effects,such as hypotension,lethargy,and drug addiction[30].Clinical studies have shown that both body acupuncture and electroacupuncture are an effective method for treating anxiety disorders,and there are no obvious adverse reactions.Bae et al.compared preoperative acupuncture treatment with placebo treatment and found that acupuncture treatment can significantly improve the patient’s preoperative anxiety and meet the preoperative sedation requirements[31].In addition,some scholars use a more objective bispectral index of the electroencephalography to observe the effect of electroacupuncture in alleviating anxiety and found that low frequency electroacupuncture to stimulate the 7 heart’s acupoints significantly reduced bispectral index of the electroencephalography and the effect was more significant than using a single dose of 10 mg of diazepam,which may be related to stimulating the release of endogenous opioids[32].In fact,different types of acupuncture and moxibustion,acupoints,and duration can alleviate anxiety to a certain extent[30].At present,there are few studies on electroacupuncture in preoperative anxiety,more clinical studies are still needed to prove its clinical effect.Follow-up studies can focus on stimulation frequency,timing,and intensity.

Effect of electroacupuncture on intraoperative and postoperative pain

In daily clinical anesthesia,intraoperative and postoperative pain caused by surgery not only affects the operation and effect,but also brings physical and psychological trauma to the patient,and affects the postoperative functional recovery and quality of life of the patient.At present,the clinical methods used to treat pain are mainly opioids,local anesthetics,non-steroidal drugs and N-methyl-D-aspartic acid receptor antagonists[33].Studies have shown that electroacupuncture can replace opioids as an important method for pain relief,which can not only reduce the dosage of opioids during and after surgery,but also reduce the incidence of respiratory depression,heart rate reduction,nausea and vomiting and other adverse events[34].Electroacupuncture-assisted analgesia has been widely studied by scholars,and it has been proven to be used for the treatment of perioperative pain in various operations.β-endorphin is one of the three family members of human endogenous opioid peptides and plays a role in the regulation of pain and immunity.Electroacupuncture stimulation can increase plasmaβ-endorphin concentration,reduce postoperative pain and reduce the use of postoperative analgesics[35].Zhang et al.divided thyroid surgery patients into two groups,cervical plexus block alone as control group and cervical plexus block combined with electroacupuncture stimulation as observation group,and found that the observation group had a lower visual analogue score.Electroacupuncture inhibited the levels of adrenocorticotropic hormone and C-reactive protein at various time points after the operation,and promoted the release ofβ-endorphin,thereby producing analgesic effects during the perioperative period and reducing the body’s fatigue[36].A meta-analysis of electroacupuncture intervention for pain after total knee replacement found that postoperative use of electroacupuncture to stimulate Futu(ST32),Yanglingquan(GB34),Zusanli(ST36),Xuehai(SP10)and Yinlingquan(SP9)can effectively alleviate the pain response after total knee replacement[37].Electroacupuncture,as a non-drug auxiliary analgesic method,has fewer side effects and its clinical effect is significantly better than that of pure drug analgesia.However,electro-acupuncture during perioperative analgesia needs to select different acupuncture points according to different surgical sites to achieve the most satisfactory results.Therefore,clinical use requires professional systemic acupoint analgesia guidance.

Effect of electroacupuncture on PONV

PONV is one of the common complications after surgery,usually with an incidence of 20%-30%,and the incidence of patients with high-risk factors can be as high as 70%-80%[38].PONV not only increases the patient’s hospital stay but also increases the medical expenses,causes water and electrolyte disturbances,aspiration pneumonia,aggravate wound pain,and affect wound healing.Although with the development of the medical level,a variety of interventions have been used clinically to reduce PONV,and the incidence has dropped to＜10%[39],but the side effects brought by it still cannot be ignored.Clinically,drugs are mainly used for antiemetics,which may cause adverse reactions such as sedation,headache,drowsiness,and dizziness[39].In recent years,electroacupuncture,used as a physical therapy to prevent and treat PONV,has been found that it has better curative effect and fewer side effects,and is worthy of popularization.At present,the main points used to relieve the symptoms of PONV are Neiguan(PC6),Hegu(LI4)and Zusanli.Neiguan is the collateral point of the pericardium meridian of Hand-Jueyin,which can calm the mind and nerves,regulate Qi and relieve pain;Hegu is the original point of the large intestine meridian,which can rise and fall the energy and unblock the blood[40]；Zusanli is a combined point under the Stomach Meridian of Foot-Yangming,which generates stomach Qi and dampens spleen[41].Tian studied the effects of electroacupuncture at different times on PONV.The experimental group chose Neiguan,Hegu,Zhigou(SJ6)and Quchi(LI11)points to retain needles for 30 minutes,and the control group used patients in the granisetron group that received intravenous injection 30 minutes before surgery.It was found that the incidence of nausea and vomiting at 24 hours postoperatively in the control group was significantly higher than that in the test group[40].Li et al.elected Neiguan and Zusanli acupoints during the study and kept the needles for 30 minutes,turns out that electroacupuncture treatment one day before surgery can effectively prevent PONV[42].However,Park et al.used electroacupuncture to stimulate Zusanli and Neiguan 1 hour before and 6 hours after thyroidectomy in an experiment to study electroacupuncture to prevent nausea and vomiting after thyroidectomy.The results showed that electroacupuncture did not affect the incidence of PONV within 36 hours after surgery[43].Therefore,the timing of stimulation with electroacupuncture to prevent PONV is still unclear.There are different results of stimulation before,during and after surgery.Further research is needed to determine the best timing of stimulation,and the experimental results may differ from individual patients,electrical acupuncture stimulation frequency and other factors.

Effect of electroacupunctureon POCD

POCD is a central nervous system complication that often occurs after surgical anesthesia in elderly patients which clinical manifestations are cognitive impairments such as memory,attention,orientation,and understanding after surgery,and can last for several weeks,months or even more.A large number of studies have shown that POCD in the elderly after general anesthesia is closely related to the occurrence and development of Alzheimer’s disease[44].At present,the pathogenesis of POCD is not yet clear[45],but neuroinflammation and oxidative stress play a key role in the progression of POCD,especially hippocampal neuroinflammation[46,47].

A large number of animal experiments have proved that electroacupuncture can improve POCD and brain protection by reducing neuroinflammation or inhibiting oxidative stress.α7-nicotinic acetylcholine receptors lays a regulatory role in the cognitive process,Liu et al.established a POCD rat model in the study and found that electroacupuncture can enhance the cognitive function of rats by increasing the expression ofα7-nicotinic acetylcholine receptors and inhibiting neuroinflammation[46].Some scholars believe that electroacupuncture can reduce POCD through the microglia/toll-like receptor 4/2 signaling pathway and improve the spatial memory of rats after surgery[47].Yuan et al.studied the effects of electroacupuncture on the cognitive function of elderly rats after acute myocardial ischemia reperfusion by observing the pathological examination,oxidative stress level and systemic inflammatory response in the hippocampal CA1 area,and found that electroacupuncture may be a neuroprotective therapy,which reduces brain damage and POCD[48].In addition,electroacupuncture can also significantly reduce cognitive impairment in POCD rats by inhibiting astrocyte activation and oxidative stress[49].These animal experiments provide theoretical support for the clinical application of electroacupuncture.Clinically,pretreatment with electroacupuncture 30 minutes before induction of anesthesia significantly reduces the dosage of opioids used in the operation and significantly improves POCD in elderly patients,which may attributed to reducing inflammation[50].Acupuncture has a certain curative effect in preventing POCD,and has no toxic side effects,and has high clinical application value.Many studies have proved that electroacupuncture can improve POCD in a variety of ways,but the specific mechanism needs further research.

Limitations

Although the role of electroacupuncture in anesthesia has been recognized by many scholars,the specific mechanism of electroacupuncture analgesia has not yet been elucidated.The current research only suggests that electroacupuncture stimulation may exert analgesic effect by regulating the function of the immune system,however,the specific regulatory pathways are still lacking,further research is needed to clarify the role of electroacupuncture analgesia in different causes and different parts,and to expand its scope of use.The use of electroacupuncture will produce fatigue effects and the stability of acupuncture,the selection of acupoint optimization will affect its therapeutic effect.At present,there is still no unified standard for the time,frequency,and intensity of electroacupuncture during perioperative period,which may affect its wide application.

Conclusion and prospects

Electroacupuncture is an effective analgesic method,which can increase the pain perception threshold and tolerance threshold.After combined anesthesia,the dosage of intraoperative anesthetics is reduced,which is more conducive to the stability of the circulatory system,and the recovery time of patients after surgery is shortened,and anesthesia-related complications are reduced.With the promotion of comfort medicine,electroacupuncture combined with anesthesia conforms to the new concept of enhanced recovery after surgery in recent years.In the future,more multi-center randomized controlled studies of electroacupuncture anesthesia are needed to provide more convincing evidence-based evidence to further promote its application.