Zhu Yi-hui(朱熠慧),Chen Sheng-xing (陳升星)

Changxing Hospital of TraditionalChineseMedicine, Zhejiang Province,Zhejiang 313100,China

Abstract

Keywords:AcupunctureTherapy;Electroacupuncture;AcupunctureAnalgesia;AcupunctureAnesthesia;Pain,Postoperative; StomachNeoplasms; Postoperative Complications; Stress

Stomach cancer is a commonmalignant tumor.In China, the incidence and mortality of gastric cancer are attheforefrontof malignant tumors[1]. Theradical surgery andothersurgicaltreatmentsarethefirst choiceforgastriccancer,whichcansignificantly improve the 5-year survival rate of patients[2]. However,dueto thegreatsurgicaldamagetothebody,the inevitablepainandstressreactions canprolong the postoperativehospitalstay,increasehospitalization costs, decrease of quality of life, and even affect the long-termsurvival[3].Therefore,how toeffectively relievethepainandstressresponseafter radical surgery isessential to thepostoperativerecovery of patients and prognosis of the disease.

Acupuncture-assistedanesthesiacanreducethe dosageof anesthetics,shorten therecovery time of anesthesia, relieve the surgical side effect, and promote the postoperative recovery[4-5]. However, there are few studiesontheapplicationof acupuncture-assisted anesthesia in radical surgery for stomach cancer, neither on its effect on postoperative pain or stress response. In this study,weappliedelectroacupunctureplusdrug anesthesia to patientsundergoing radical surgery for stomachcancer,andobservedbody stress response items such as pain degree, blood pressure and heart rate, and tested the levels of serum β-endorphin (β-EP)and adrenocorticotrophic hormone (ACTH).

1 Clinical Materials

1.1 Diagnostic criteria

Those whomet the diagnostic criteria of stomach neoplasms intheGuidelines for theDiagnosis and Treatment of Gastric Cancer(2011 Version)[6]: lack of specific clinicalsymptoms,withcommonclinical symptoms suchas epigastriumdiscomfort,pain,decreasedappetite,marasmus,fatigue,hematemesis andblack stool;noobvioussignsinearly or some advancedgastric cancer;palpableupper abdominal massinadvancedcases;confirmedby gastroscopic pathological biopsy.

1.2 Inclusion criteria

Those who met the above diagnostic criteria; who requiredelectiveradicalgastrectomy under general anesthesia;aged18-70 years;anesthesiarisk scale gradedⅠ-Ⅱ;patientsandtheir familieswerefully awareof thestudy process,andsignedinformed consent.

1.3 Exclusion criteria

Thosewithprevioushistory of major abdominal surgery;womenduring pregnancy or breastfeeding;who hadreceivedradiotherapy or chemotherapy before surgery; those with severe heart, lung, liver or kidney diseases;whohadinfectionsinacupuncture areas; who was unconscious and unable to cooperate.

1.4 Elimination and shedding criteria

Those presenting withsevereadversereactions during or after surgery; those got worse during the trial;who dropped out during the trial; loss of data or with incomplete clinical materials.

1.5 Statistical methods

Alldatawerestatistically analyzedby theSPSS version 20.0 statistical software. Measurement data in normal distribution and having homogeneous variance were expressed as mean ± standard deviation (±s).Two-way repeated measures ANOVA was applied to the intra-groupcomparisonsat different timepoints.One-way repeated measures ANOVA was applied to the comparisons between groups at the same time points.Chi-squaretest wasappliedto thecomparisons of counting data.P＜0.05was consideredtoindicate a statistically significant difference.

孫家棟 中國(guó)航天科技集團(tuán)有限公司高級(jí)技術(shù)顧問，風(fēng)云二號(hào)衛(wèi)星工程總設(shè)計(jì)師，北斗二號(hào)衛(wèi)星工程和中國(guó)第二代衛(wèi)星導(dǎo)航系統(tǒng)重大專項(xiàng)高級(jí)顧問，原航空航天工業(yè)部副部長(zhǎng)

1.6 General data

A totalof 60 patientswithstomachneoplasms undergoing elective radical gastrectomy under general anesthesia were enrolled between January 2016 and May 2019. All cases were divided into a control group and an observation group according to the method of random number table, with 30 cases in each group. The patientsinthe observationgroupagedbetween50 years and 70 years, with surgical time ranging between 90 min and 180 min. The patients in the control group aged between 50 years and 68 years, with surgical time ranging between 93 min and 179 min. There were no significant differences in the data of gender, age and surgicaltimebetweenthe twogroups (allP＞0.05),indicating that the two groups were comparable (Table 1).

Table 1.Comparison of the general data between the two groups

2 Anesthesia Methods

2.1 Control group

Patients inthecontrolgroupwere givendrug anesthesia.First,patients weregivenanesthesia induction: intravenous sufentanil (China Food and Drug Administration approval number: H20054172, Yichang HumanwellPharmaceuticalCo.,Ltd.,China)0.4 μg/(kg·bw),etomidate(ChinaFoodandDrug Administration approvalnumber:H20020511, Jiangsu Nhwa Pharmaceutical Co., Ltd., China) 0.25 mg/(kg·bw),midazolam(ChinaFoodandDrug Administration approvalnumber:H10980025,JiangsuNhwa PharmaceuticalCo.,Ltd,China) 0.05mg/(kg·bw) and cisastracuriumbesilate(ChinaFoodandDrug Administration approvalnumber:H20060869, Jiangsu Hengrui Pharmaceutical Co., Ltd., China) 0.2 mg/(kg·bw).Afterwards, thepatients received trachealintubation and mechanical ventilation quickly. During the surgery,propofol (China Food and Drug Administration approval number:J20160042,Beijing Fresenius Kabi Pharmaceutical Co., Ltd., China) 4 mg/(kg·bw) per hour and remifentanil (China Food and Drug Administration approvalnumber:H20030200,YichangHumanwell PharmaceuticalCo.,Ltd.,China)0.3μg/(kg·bw)per hour were giventomaintainanesthesia.After the surgery,thepatient-controlledanalgesiapumpwas used for continuous analgesia with sufentanil 200 μg plus 0.9% normalsaline200mL,andintravenous infusion rate was set at 2 mL/h. When the patient still felt pain under the continuous dose, he could press the‘self-control’ button to add one more dose. The dose was set by the anesthesiologist at 0.5 mL.

2.2 Observation group

Patients in the observation group were treated with additional electroacupuncture besides drug anesthesia.On the surgery day, the patients received continuous electroacupuncture stimulation beginning from 30 min before the anesthesiainductiontilltheendof the surgery.

Points: Bilateral Hegu (LI 4), Neiguan (PC 6), Zusanli(ST 36) and Taichong (LR 3).

Methods: The sterile acupunctureneedles (Suzhou MedicalApplianceFactory,China)of 0.30 mmin diameter and 40 mm in length were used. After routine disinfection,the physicianperpendicularly punctured theabovepointsby finger-pressingneedleinserting method.After thepatients hadfeeling of soreness,numbness,distentionorpain,evenreinforcing- reducing manipulationwasperformed.Thenthe handles of the needles were connected [on the same side, Hegu (LI 4) and Neiguan (PC 6) as a group, Zusanli(ST 36) and Taichong (LR 3) as a group, a total of 4 sets of electroacupuncture]toHwatobrandSDZ-Ⅱelectroacupunctureapparatus (SuzhouMedical ApplianceFactory, China), with sparse-dense wave at 2Hz/100 Hz. Theintensity was set according to the patient’s tolerance.

3 Observation of Results

3.1 Observation items

3.1.1 Visual analog scale (VAS) score

VAS score was used to assess the paindegreeof patients before anesthesia, and 2 h, 12 h and 24 h after surgery. The VAS score ranged from 0 to 10 points. 0 represented no pain and 10 points represented extreme pain[7]. Thepatient wasaskedtomark apoint that represented the degree of the pain on a 10-centimeter line, and the physician recorded the score of the pain degree according to the patient’s mark.

3.1.2 Hemodynamics items

3.1.3 Laboratory test items

The venous blood of the patient was collected before anesthesia, and 2 h, 12 h and 24 h after surgery. The levelsof serumβ-EP andACTHweremeasuredby radioimmunoassay.

3.2 Results

3.2.1 Comparison of the VAS score

Therewas nosignificant differenceinVAS score between the two groupsbefore anesthesia(P＞0.05).The VAS scores 2 h, 12 h and 24 h after surgery in both groups were higher than those before anesthesia (allP＜0.05). The VAS scores in the observation group were all lower than those in the control group at the three time points (allP＜0.05), (Table 2).3.2.2 Comparison of the heart rate

Therewasnosignificant differenceinheartrate between the two groupsbefore anesthesia(P＞0.05).The heart rates at 2 h, 12 h and 24 h after surgery in the control group were all significantly higher than those before anesthesia (allP＜0.05). The heart rates of the observationgroupat thethreetimepointshadno significant differences from those before anesthesia (allP＜0.05), and were all lower than those in the control group at the same time points (allP＜0.05), (Table 3).

3.2.3 Comparison of the mean arterial pressure

Therewasno significantdifferenceinthemean arterialpressurebetweenthe twogroups before anesthesia (P＞0.05). The mean arterial pressures at 2 h,12 h and 24 h after surgery in the control group were all significantly higher than thosebeforeanesthesia(allP＜0.05). The mean arterial pressures of the observation groupat thesametimepoints hadnosignificant differences from those before anesthesia (allP＜0.05),and were all lower than those in the control group at the same time points (allP＜0.05), (Table 4).

3.2.4 Comparison of the serum β-EP level

There was no significant difference in the serum β-EP levelbetweenthetwogroupsbeforeanesthesia(P＞0.05). Two hours, 12 h and 24 h after surgery, the serumβ-EPlevelsof theobservationgroupwere significantly higher than thosebeforeanesthesia(allP＜0.05), and were all significantly higher than those in the control group at the same time points (allP＜0.05),(Table 5).

3.2.5 Comparison of the serum ACTH level

Therewas no significant differenceintheserum ACTH level between the two groups before anesthesia(P＞0.05). The serum ACTH levels at 2 h, 12 h and 24 h after surgery in the control group were all higher than those before anesthesia (allP＜0.05). The serum ACTH levelin theobservationgroup was higher than that before anesthesia only at 2 h after surgery (P＜0.05). The serum ACTH levels in the observation group were all significantly lower than those in the control group at the same time points (allP＜0.05), (Table 6).

Table 2.Comparison of VASscorebetween the twogroups ( ±s, point)

Table 2.Comparison of VASscorebetween the twogroups ( ±s, point)

Note:Compared with the same group before anesthesia,1) P＜0.05;compared with the control group at the same time point, 2) P＜0.05

GroupnPre-anesthesia 2h after surgery 12h after surgery 24h after surgery Observation 300.99±0.583.81±0.911)2)2.48±0.831)2) 1.17±0.541)2)Control 300.95±0.665.77±1.191) 4.40±0.951)2.93±0.551)

Table 3.Comparisonof heart rate betweenthe twogroups(±s,time/min)

Table 3.Comparisonof heart rate betweenthe twogroups(±s,time/min)

Note:Compared with the same group before anesthesia,1) P＜0.05;compared with the control group at the same time point, 2) P＜0.05

GroupnPre-anesthesia 2h after surgery 12h after surgery 24h after surgery Observation 3070.67±6.3671.07±9.962)69.83±6.272) 69.82±4.932) Control 3068.60±5.5783.53±9.041)75.60±3.791) 71.90±4.211)

Table 4.Comparison of meanarterial pressure between the twogroups( ±s, mmHg)

Table 4.Comparison of meanarterial pressure between the twogroups( ±s, mmHg)

Note:Compared with the same group before anesthesia,1) P＜0.05;compared with the control group at the same time point, 2) P＜0.05

GroupnPre-anesthesia 2h after surgery 12h after surgery 24h after surgery Observation 3078.79±6.2681.66±6.082)78.86±6.312) 80.00±6.132) Control 3079.03±5.3397.61±5.621)92.02±7.151) 85.86±4.931)

Table 5.Comparisonof the serum β-EP level betweenthe twogroups(±s, pmol/L)

Table 5.Comparisonof the serum β-EP level betweenthe twogroups(±s, pmol/L)

Note:Compared with the same group before anesthesia,1) P＜0.05;compared with the control group at the same time point, 2) P＜0.05

GroupnPre-anesthesia 2h after surgery 12h after surgery 24h after surgery Observation 30 232.28±17.13396.57±18.981)2) 358.76±21.171)2)305.53±13.881)2)Control 30 231.19±18.81237.51±18.33222.47±16.27 220.68±21.87

Table 6.Comparisonof theserum ACTH level betweenthe twogroups( ±s, pg/mL)

Table 6.Comparisonof theserum ACTH level betweenthe twogroups( ±s, pg/mL)

Note:Compared with the same group before anesthesia,1) P＜0.05;compared with the control group at the same time point, 2) P＜0.05

GroupnPre-anesthesia 2h after surgery 12h after surgery 24h after surgery Observation 3024.85±3.1429.92±2.891)2) 25.21±2.742) 25.01±2.832) Control 3024.95±3.0855.16±2.951)52.69±4.211) 29.27±3.071)

4 Discussion

Radicalgastrectomy is the mostimportant and effectivetreatmentfor gastric cancer.However,regardless of laparoscopic or open radical gastrectomy,it is an important irritant stressor and can cause pain andstress responseinpatients during perioperative period[8]. Postoperative pain is often acute, if the early postoperative analgesic effect is not satisfactory, it may develop into chronic persistent pain[9]. Stress reaction can break the homeostasis of the body, increase oxygen consumption,causeimmunosuppression,abnormal blood pressure, arrhythmia, and hypercoagulable state,further leading to neuro-endocrine-immunesystem disorders[10]. Pain is closely related to stress response and they can affect each other. Pain is the continuation or externalmanifestationof postoperativestress response, and stress response often fluctuates due to the change of pain degree[11].

The levels of serum β-EP and ACTH can reflect the patient's pain and stress response to some extent. β-EP isanendogenousopioidpeptide,mainly fromthe hypothalamusandpituitary gland.It has astrong analgesic effect.It is regulatedby adrenocortical hormonereleasing hormone,andcanautonomously protect homeostasis and pain regulation[12]. Generally,stress can cause the reactive increase of serum β-EP level[13]. ACTH is a peptidehormone secreted by the adenohypophysis, which can promote the proliferation of adrenal cortex and the synthesis and secretion of glucocorticoidandmineralocorticoid.Thestress response canmake anterior pituitary release alarge amount of ACTHby stimulating thehypothalamic- pituitary-adrenal cortex axis[14]. The increase of ACTH level in surgical patients can more sensitively reflect the severity of the body's stress response.

Theclinicalapplicationof acupuncture-assisted anesthesia has a long history. Luo YY,et al[15]applied acupuncture combined with propofol in patients during painless colonoscopy examination. The results showed that comparedtopropofolanesthesiaalone,acupuncture combined with propofol could significantly reducetheplasmacortisollevelandfasting blood glucoselevel, and the changes of heart rate, systolic pressure and diastolic pressure were comparatively less significant,withsmaller dosageof propofol.It suggestedthatthecombinedanesthesiaof acupunctureanddrug couldeffectively suppress the stress responseof patients,stabilizehemodynamics,avoid theinfluenceof hemodynamic fluctuationson organs,andhelptoreducetheadversereactions caused by anesthetics and improve surgery safety. Qu N,et al[16]applied acupunctureplusdrug anesthesia to elderly patients undergoing hipreplacementsurgery andfoundthatcombinedwithacupuncture,the fluctuationof heartrateandmeanarterialpressure were effectively reduced, the dosages of propofol and remifentanil were reduced, and the VAS scores at 6 h,12 h and 24 h after surgery were significantly decreased,and the pain was relieved during perioperative period.It can be seen that acupuncture-assisted anesthesia has thecharacteristics of analgesia,sedationandsafety,which is helpful to maintain the stability of the internal environment and promote postoperative recovery.

Chinesemedicinebelieves that anesthesiasurgery may damagethe functionsof theZang-fuorgans,obstruct theflow of qiandblood,andresultin disorders of qi,blood,yinandyang of the Zang-fu organs.Acupuncturecanunblock meridianqiby stimulating specific points, so as to maintain the body in aharmoniousstate[17].Theanalgesic andsedative effects of acupuncture anesthesia are mostly related to the regulation of central nervous system activity. Some studies have suggested that acupuncture could induce thereleaseof centralneurotransmitters and endogenous opioid peptides (such as β-EP, substance P,etc.) to exert analgesic effect, and it could exert sedative effectby regulating thelimbic systemof the hypothalamus.Besides,it couldalsoinhibitthe excessivereleaseof inflammatory mediatorsto suppress stressresponsessuchashemodynamic changes[18].

In this study,Hegu(LI 4),Neiguan(PC 6), Zusanli(ST 36)andTaichong (LR 3)wereselectedfor electroacupuncture.Hegu(LI4)isthe Yuan-Primary point of the Large Intestine Meridian. It can invigorate qi and promote blood circulation. Taichong (LR 3) is the Yuan-Primary point of the Liver Meridian.It can replenishbloodandregulateblood circulation.Hegu(LI 4) and Taichong (LR 3) are called ‘Four Gate Points’.They can simultaneously adjust yin and yang, qi and blood,and Zang-fuorgans, andsignificantly alleviate pain.Meanwhile, they can suppresshyperactiveliver yang,inhibit endogenous wind, tranquilize themind,activate blood andresolve stasis, andharmonize the intestines andstomach.Neiguan(PC 6)isthe Luo-Connecting point of the Pericardium Meridian. It is one of the Eight Confluent Points to connect with the YinLink Vessel.It acts to calm themind, fortify the spleen, harmonize the stomach, stabilize the heart rate and blood pressure, and relieve pain[19]. Zusanli (ST 36)is the He-Sea point of the Stomach Meridian and the lower He-Sea point of the stomach. It acts to unblock meridians, strengthen the healthy qi, benefit the spleen and stomach and relieve pain. It is a key point for health care. It can boost the immune system, improve heart function,andregulate thehypothalamus-pituitary- adrenal system, reduce stress response[20].

Theresultsinthisstudy suggestedthat the postoperativeVAS scoresinpatientsreceiving electroacupunctureplusdruganesthesiawerelower than those in the control group, and the heart rate and the blood pressure were stable, the serum β-EP levels were increased, and the serum ACTH levels were stable.All these results indicated that electroacupuncture plus drug anesthesia can significantly relieve pain, suppress stressresponseinpatientsundergoing radical gastrectomy, and is worth clinical application.

Conflict of Interest The authorsdeclarethat there isnoconflict of interest.Statement of Informed Consent Informed consent wasobtained from all individual participants.

Received:26 September 2019/Accepted:31October 2019