Effect of wrist-ankle acupuncture on propofol dosage during painless colonoscopy: A randomized controlled prospective study

lNTRODUCTlON

Wrist-ankle acupuncture was developed by Professor Zhang Χinshu from the Department of Psychiatry and Neurology, the First Affiliated Hospital of the Second Military Medical University of the Chinese People’s Liberation Army. Inspired by acupuncture, acupuncture points and acupuncture method, a therapy gradually developed from practice. Wrist-ankle acupuncture is the abbreviation of wrist-ankle acupuncture therapy. It refers to the method of selecting a specific needle entry point at the wrist and ankle and piercing a certain length along the longitudinal axis of the limb along the subdermis to treat diseases. Compared with other acupuncture therapies, it has the characteristics of simple acupoint selection, long needle retention time, safety and reliability and no side effects. Therefore, the operation of wrist-ankle acupuncture is simpler and does not require electric acupuncture and other equipment,so it is easier to apply in anesthesia[1-2].

Colonoscopy is the gold standard for diagnosing lower gastrointestinal diseases. However, it is an invasive examination that inevitably brings pain to the examinee. To deal with that, painless colonoscopy is commonly applied clinically for examination. The most adopted anesthetics for painless colonoscopy at the moment primarily consist of intravenous anesthetics and anesthetic sedatives,among which propofol and etomidate are the most common ones[3-4]. In terms of its clinical superiority, painless colonoscopy can reduce patients' fear and discomfort and improve the detection rate of disease. Propofol is characterized by quick effect and short action time, which is a common choice of sedative and anesthetics in painless endoscopy. However, propofol can cause severe respiratory and circulatory inhibition. Therefore, it is of great clinical significance to find an approach to reduce the dose of propofol. Recent application of acupuncture anesthesia has gradually achieved good results in the field of digestive endoscopy[5]. Accordingly, this study was carried out to analyze whether wrist-ankle acupuncture during painless colonoscopy can reduce the induction dose and total dose of propofol, so as to reduce the occurrence of related complications.

MATERlALS AND METHODS

Clinical case data

The subjects of this study were 200 patients who were going to receive selective painless colonoscopy in Hebei Hospital of Traditional Chinese Medicine from August 2019 to November 2019. Enrolled patients were divided into wrist-ankle acupuncture group (WAA group,=100) and control group (CON group,= 100) based on the random number table method. Finally, 91 cases were included in WAA group and 90 cases in CON group after the exclusion of 19 cases from the study due to prolonged operation time (＞30 min) (Figure 1).

沼肥對我國農業可持續發展重要性研究………………… 畢婷婷，尹 芳，王翠仙，譚少杰，王昌梅，趙興玲，吳 凱，張無敵（76）

Inclusion and exclusion criteria

(1) Patients 18-79 years old; (2) American Society of Anesthesiologists classification of grade I-II; and (3) No contraindications for colonoscopy.

(1) Patients who refused painless colonoscopy; (2) Pregnant woman; (3) Patients with allergic history of propofol injection; (4) Patients who were intolerant to opioids; (5) Patients who took potential neuromodulatory drugs (, diazepam,) before operation; (6) Patients with cerebrovascular accident; (7) Patients with a history of craniocerebral injury or neurosurgery; (8)Patients with impaired verbal communication; (9) Patients with mental disorder; and (10) Patients with infection at the puncture site.

(1) Patients with prolonged operation time ＞ 30 min; (2) Patients who voluntarily withdrew from the operation; and (3) Patients who were not anesthetized or operated as required after inclusion. Nineteen cases were rejected for prolonged operation time. The purpose of these criteria was to unify the control standards and to count the rejected cases as attrition. These patients were recorded in the same way as the other patients, but the early data of the cases are not included because these cases are not unified control standards.

This study has been registered in China Clinical Trial Registration Center (registration code:ChiCTR1900022177,http://www.chictr.org.cn/). This study has been approved by the Medical Ethics Committee of Hebei Hospital of Traditional Chinese Medicine, with informed consent signed by all patients.

在科學史上，許多優秀科學家為堅持和捍衛真理或遭受挫折，或付出沉重代價甚至生命的例子比比皆是。布魯諾、伽利略因支持宣傳日心說，遭羅馬教廷的殺害與監禁；哥倫布、徐霞客勇往直前地探索大自然的秘密；為進一步尋找大陸漂移的證據，魏格納只身前往格陵蘭島腹地，不幸在他50歲生日那天遇難……這些都是對學生進行情感、態度與價值觀培養的絕佳素材。所以在教學中，應努力營造地理科學史教育的氛圍，讓學生感同身受這些科學家們的人格魅力。

Operation and anesthesia procedure

Enrolled patients were divided into WAA group and CON group based on the random number table method. The allocation was concealed in an opaque envelope. An anesthesiologist trained in wrist-ankle acupuncture was responsible for unsealing the envelope prior to wrist-ankle acupuncture and then performed accordingly but was not responsible for patient care or collection of variable data related to the research. Another anesthesiologist was only in charge of intraoperative management of all patients and was blinded to patient grouping. Meanwhile, the endoscopist (the same physician for colonoscopy)and the nurse (the same trained nurse) were both blinded to the grouping of patients.

As shown in Table 1, there was no significant difference in sex, age, body mass index and operation time of examination between the two groups (＞ 0.05).

Observational indexes

Wrist-ankle acupuncture can reduce the induction dose and total dose of propofol as well as the incidence of adverse reactions in painless colonoscopy without affecting the satisfaction of examiners and patients. This procedure is simple in operation and easy to promote in clinical practice.

The examiners' satisfaction and patients' satisfaction: After the examination, the endoscopist and patients used the VAS scale of 0-10 points to evaluate satisfaction with the examination.

三年來，企業大力宣貫合規管理重要意義，制定合規管理制度，組織全員學習《誠信合規手冊》和《通用法律禁止性和規范性指引》，簽訂誠信合規承諾書；建立并完善合規管理信息平臺，構建合規管理體系框架；在線完成全員合規培訓、上下級合規培訓及合規評價；組織合規管理人員和新入職員工合規培訓，推進合規管理工作規范開展。明確并強化“管業務必管合規”的責任制，把合規要求體現到制度設計、業務部署、業績考核及職務晉升之中，促進合規業務部門合規責任落實。

Statistical and analysis

Reducing the induction dose and total dose of propofol can greatly decrease the complication related to anesthesia during painless colonoscopy. In this study, the mechanism of wrist-ankle acupuncture to reduce the anesthetic dose may be that acupuncture increases cerebral blood flow[18] and changes the permeability of blood-brain barrier[19], resulting in the enhanced permeability of blood-brain barrier to propofol and accelerated onset time of propofol, thus reducing the induction dose of propofol. Inpractice, our data indicated that many patients had opened their eyes at the end of examination.However, patients in WAA group had less complaints, movements or painful expressions, and there was no impact on the examination of the patients, leading to a reduced propofol dose in this group. The decreased demand for propofol in the process is speculated to be related to the good analgesic effect of wrist-ankle acupuncture[20-22].

SPSS 23.0 (Armonk, NY, United States) and GraphPad Prism 7.0 (San Diego, CA, United States) were used for data processing and plotting. Measurement data of normal distribution is expressed as mean ±standard deviation (`x ± s), and the measurement data of non-normal distribution is represented by median (interquartile spacing).test was used to compare the counting data. Rank-sum test was used for non-normal distribution measurement data in both groups. The measurement data of normal distribution between the two groups were tested by two independent sampletest. Besides, the fatigue index was measured by repeated measurement design analysis of variance.＜ 0.05 indicates the difference was statistically significant.

人們對現實世界的認知,總是遵循由近及遠,由易到難,由簡單到復雜,由已知到未知,由具體到抽象的思維規律;遵循由直接到間接,由關聯性較多到關聯性較少,由關聯很強逐漸過渡到關聯很弱的邏輯順序和認知規律。

RESULTS

Comparison of general materials

Patients were informed to keep fasting status for 12 h and receive catharsis prior to the examination with the confirmation that no medication was taken before anesthesia. Prior to anesthesia, patients in WAA group were punctured by skilled personnel in the inferior 1, 2 and 3 regions using the needling instrument of filiform needle (No. 32, 1 inch, 0.25 mm × 25 mm in diameter; Hwato, Suzhou, China)according to the zoning principle of wrist-ankle acupuncture (Figure 2). During the operation, patients in both groups were lying on their left side and were given oxygen by nasal catheter (6 L/min),associated with the monitoring of blood pressure, heart rate and pulse oxygen saturation (SpO). Before the injection, the patients were asked to take several deep breaths, followed by intravenous injection of nabufine (0.025 mg/kg) and infusion of propofol (0.5 mg/kg). After waiting for 5 s, patients who did not fall asleep were given another 10 mg of propofol per time as appropriate. Colonoscopy was not performed until the disappearance of eyelash reflex and no response after calling. When there was movement, frowning and hemodynamic changes (heart rate ＞ 20 times/min, systolic blood pressure ＞20% of the basic value) in the patients during operation, additional propofol (10 mg/time) was provided until the patients were unconscious again. During colonoscopy, there was no need for adding propofol when patients opened their eyes without painful expression or movement.

Comparison of related indexes during anesthesia

As shown in Table 2, the propofol induction dose and total propofol dose of WAA group was 80 mg and 110 mg, respectively, which were significantly lower than those of CON group (＜ 0.05).

The incidence of hypoxemia and hypotension in WAA group was 2.2% and 3.3%, respectively, which were significantly lower than those in CON group (＜ 0.05).

The incidence of abdominal distention in WAA group was 8.8% (8 cases), which was significantly lower than that in CON group (＜ 0.05). There was no significant difference in the incidence of nausea and vomiting between the two groups (＞ 0.05), as listed in Table 2.

Comparison of related indexes after anesthesia

The wake-up time in WAA group was 3.26 ± 0.87 min, which was significantly lower than that in CON group (6.06 ± 0.88 min,＜ 0.05). The VAS score of pain between 15 min and 30 min in WAA group after entering the recovery room was 1.38 ± 0.49 and 0.65 ± 0.48, respectively, which were significantly lower than those in CON group (2.31 ± 0.47 and 1.89 ± 0.32,＜ 0.05). Although the VAS scores of pain between 30 min in both groups were lower than their counterparts between 15 min, the downswing of VAS score in WAA group was even more remarkable than in CON group. Meanwhile, the Borg fatigue index 5 min after entering the recovery room in WAA group was 1.74 ± 0.697, which was significantly lower than that in CON group (＜ 0.05). No statistically significant difference was observed between the two groups in Borg fatigue index 30 min after entering the recovery room (＞ 0.05).

As to patients' satisfaction and examiners' satisfaction about the whole examination, there was no significant difference in the VAS score of patients' satisfaction between the two groups (＞ 0.05), but the VAS score of examiners' satisfaction in WAA group (9.89 ± 0.31) was higher than that in CON group (＜ 0.05) (Table 3).

DlSCUSSlON

Propofol and opioids are the most commonly used painless drugs clinically. However, each of these drugs causes respiratory depression[6], and the combined use of midazolam or propofol with opioids may further increase the risk of hypoxemia and apnea[7-8]. According to the statistics of reviews related to claims in medical accidents, respiratory depression caused by excessive sedation plays a key role in painless treatment of patients' injuries[9]. The rate of respiratory and hemodynamic complications reached 10.?%-14.5% when using propofol for painless treatment[10-11]. Nowadays, attempts have been made to introduce other methods to reduce the dose of propofol, so as to reduce the side effects of propofol. It has been studied that a combined use of naborphine and propofol can provide safer anesthesia effect[12]. Besides, non-pharmaceutical methods, such as acupuncture combined with anesthesia, can also reduce the dose of narcotic drugs. Wrist-ankle acupuncture, among those, is a significantly simple, safe and reliable acupuncture therapy[13]. Wrist-ankle acupuncture can take 5 min to realize the effect of increasing pain threshold[15]. Different from traditional acupuncture, it adopts shallow subcutaneous acupuncture without soreness and pain, which improves patient’s acceptance and achieves easy intraoperative retaining. At present, wrist-ankle acupuncture has a good effect on dysmenorrhea. It is widely accepted that the discomfort related to colonoscopy mainly comes from visceral pain secondary to colon expansion and traction[17]. The authors support the theory that it is similar to visceral pain such as dysmenorrhea. Therefore, wrist-ankle acupuncture was applied to observe its effect on propofol dose during painless colonoscopy.

With α = 0.05 and power = 0.95 as the inspection levels, the mean and the standard deviation of CON group was 145 mg and 72.0, and the mean and the standard deviation of propofol dose was 115 mg and 45 in WAA group, according to the pre-test results. By using a two-tailed test, the sample size of each group was 88 cases by using PASS11.0 statistical software. Considering an escaping rate of 10%, 200 patients were included and randomly divided, with 100 cases in each group.

40年，鑄就了一座雄厚的經濟實力之城，同時又是一座古今輝映的文化之城。蘇州地區生產總值由1978年的不足32億元增加到2017年的1.7萬億元，列全國第七；人均GDP由634元增加到15.9萬元，列全國第三，超過葡萄牙等國家。與強大經濟硬實力相得益彰的是，蘇州又是一座古今輝映的文化之城，不僅是罕見的“雙遺產”城市，還是全國唯一的歷史文化名城保護示范區。2014年，蘇州因其在平衡經濟發展與傳承歷史文化傳統等方面的出色成績獲得李光耀世界城市獎。

Hypoxia and apnea caused by respiratory depression and airway obstruction are the most common cardiopulmonary complications of painless colonoscopy[23]. In our study, the incidence of hypoxemia and hypotension in WAA group was less than that in CON group, because wrist-ankle acupuncture can reduce the dose of propofol, especially during induction when there was a concentrated application of propofol, which might induce a higher risk of respiratory inhibition and circulatory fluctuation. In this regard, respiratory depression and hypotension were relieved in patients consequently owing to the reduced propofol dose during induction by using wrist-ankle acupuncture.

Generally, there is a need to pump air into the intestine to expand the field of vision during colonoscopy, which may produce pressure on the intestinal wall. Patients may feel abdominal pain and distention within hours or even days after the examination[24]. The movement of intestine is manifested as circular muscle contraction in fasting state after colonoscopy, which restricts the movement of colonic contents to the distal colon[25]. Abdominal distention after colonoscopy can cause anxiety and discomfort, which greatly reduce the comfort experience of patients. In this study, the incidence of abdominal distention was significantly reduced in WAA group than that in CON group (＜ 0.05). It is believed that wrist-ankle acupuncture can reduce the activity of sympathetic nerve and improve the tension of the vagus nerve to realize their balance[26]. It can thus promote intestinal peristalsis to expel expanding gases rapidly, reduce the incidence of abdominal distention and relieve the anxiety of patients. It is suggested that patients in the WAA group can wake up quickly after anesthesia. This may be related to the decrease in the dose of propofol or the increase in β-endorphin secretion caused by wrist-ankle acupuncture to regulate body fatigue. Inter-group comparison indicated that the wake-up time of WAA group was superior to that of CON group, which may be caused by the decrease of total propofol dose during the whole operation, so that the patients could wake up more rapidly from anesthesia.

Furthermore, the detection result of the Borg fatigue index was better in WAA group than that in CON group 5 min after entering the recovery room. However, no obvious statistical difference was found between the two groups 30 min after entering the recovery room.

It suggests that patients in WAA group have a rapid wake-up from anesthesia. It may be related to the reduced propofol dose, or increased β-endorphin secretion resulted from wrist-ankle acupuncture to regulate human fatigue[27-29].

After the examination of patients in the two groups, the examiners' satisfaction was improved compared with in the CON group. It can be explained that the examination turnover time was shorter in WAA group since patients in this group woke up faster, and thus it was more popular with doctors.Besides, the patients' satisfaction was similar in the two groups although the incidence of abdominal distention after examination was higher in CON group. We believe that it is related to the sufficient communication with patients before examination. Patients have sufficient understanding and expectation of the occurrence of postoperative abdominal distention and thus better postoperative acceptance. Therefore, it has no significant influence on the satisfaction of patients.

TRP通道的發現為疼痛治療開辟了一個嶄新的領域。與以往的鎮痛藥物不同，以TRP通道為靶點的新型鎮痛藥物能從源頭上消除疼痛的產生。但我們應清楚地認識到，TRP通道組織分布廣泛，生理功能多樣，以此為靶點的藥物在發揮鎮痛作用的同時往往伴隨著副作用。TRPV1拮抗劑正是因為具有體溫過高的不良反應而阻礙了其在臨床上的應用。因此，減少此類藥物的不良反應將是研發的難點。進一步研究TRP通道在疼痛中的作用對于闡明疼痛的發生機制、治療及相關藥物研發具有重要意義。

There was statistically significant difference of VAS scores between the two groups at 5 min and 15 min after entering the recovery room. However, the estimated scores were all ＜ 3 points, and the result has no significant clinical significance in our opinion. The authors consider that it may be attributed to the fact that the pain is generally mild after colonoscopy, and both groups of patients used naborphine,which may cover the symptoms of patients in CON group. There may be differences between the two groups in the case when naborphine is not used.

Meanwhile, naborphine was administrated to patients according to body weight, and thus there was no difference in the dose between the two groups.

Our study was designed as a randomized controlled study with certain limitations. It is necessary to conduct in-depth research and discussion on the related mechanism with respect to the phenomena observed in the study.

CONCLUSlON

In summary, wrist-ankle acupuncture combined with propofol can significantly reduce propofol dose during painless colonoscopy, decrease the incidence of adverse drug reactions, reduce the incidence of abdominal distention after examination, improve examiners' satisfaction and safety of colonoscopy and reduce the wake-up time of patients. Thus, drug anesthesia combined with wrist-ankle acupuncture is a feasible treatment method worthy of clinical application and promotion.

Borg fatigue index: 0 point, no fatigue; 0.5 point, extremely slight fatigue, almost imperceptible; 1 point, quite slight fatigue; 2 points, slight fatigue; 3 points, moderate fatigue; 4 points, slightly serious fatigue; 5 points, serious fatigue; 6-8 points, quite serious fatigue; 9 points, extremely serious fatigue;and 10 points, extreme fatigue, reaching the limit.

實驗結果顯示，采用PDCA管理后，我院中抽血標本、試管錯誤、漏抽血標本、登記錯誤、樣本遺失的情況較質量管理前更優，組間差異具有統計學意義（P＜0.05）。其結果說明，將PDCA管理應用于管理工作中，能夠使門診抽血室標本管理質量得到明顯提高，改善標本門診管理人員的管理質量。標本管理是醫院各項質量管理中的一項重要環節[10]。PDCA管理方案，能夠保證所有人員在工作過程中參與到計劃實施中來，從而設計并實現相應的管理目標[11-12]。

ARTlCLE HlGHLlGHTS

Research results

Wrist-ankle acupuncture combined with propofol can significantly reduce propofol dose during painless colonoscopy, decrease the incidence of adverse drug reactions, reduce the incidence of abdominal distention after examination, improve examiners' satisfaction and safety of colonoscopy and reduce the wake-up time of patients.

Research conclusions

Wrist-ankle acupuncture can reduce the induced dose and total dose of propofol, reduce the incidence of adverse reactions of painless colonoscopy and does not affect the satisfaction of the examiner and the patient.

這是首次提出“三大能力”.幾何教學目標是：使學生掌握系統的幾何知識，培養推理論證的能力，發展空間想象能力.

Research perspectives

The wrist-ankle needle is simple to operate and can reduce the dosage of propofol, and it is easy to promote in clinical practice.

Android流量監控、分析、攔截平臺采用C-S模式，客戶端實現監控和攔截功能，服務器實現惡意流量規則的匯總、判優和同步。

FOOTNOTES

Hao W and Dong YJ conceived the study; Dong YJ, He T and Liu C recruited the patients;Dong YJ performed the wrist-ankle acupuncture; He T, Li Y, Liu C, Χu Z and Lu ZΧ collected the data; Hao W analyzed the data; Hao W, Kong LL interpreted the data; He T and C Liu contributed equally; All authors read and approved the final version of the manuscript.

This study was approved by the Hebei Provincial Hospital of Traditional Chinese Medicine Medical Ethics Committee (2019-KY-003-02).

扎實推進城鄉公共文化服務一體化建設；深化文化體制改革，建立健全文化管理體系。要扎實開展精神扶貧活動，提供適合特殊群體的文化服務和產品。為廣大農民群眾提供豐富的文化產品。堅持文化惠民，完善基礎設施，激發村民的文化自覺，提高農民的整體素質，提升農民生活品質，以文化自覺成就文化自信。此外，大力宣傳鄉土文化，打造具有鄉土文化特色的景點，實現鄉村振興[9-10]。

當下，在電視媒體與新媒體融合發展的過程中，片面否定電視媒體所具有的一些能力與優勢。誤以為電視媒體與新媒體的融合發展就是以新媒體作為支撐，不斷地發展新媒體。但是，二者的融合發展要充分發揮二者的優勢，避免二者的弱勢，從而找準二者的自身定位，尋求適合的發展模式，這樣才能夠促進二者的發展。新媒體的優勢是能夠獲取更多的信息，能夠實現信息的快速、隨時隨地的傳播，宣傳面更廣；而電視媒體能夠保證傳播信息的真實有效性，這是新媒體所不具備的，因此，二者結合發展，能夠保證傳播信息的全面、高效，還能夠保證信息的真實可靠，從而更好地發展媒體行業。

This study has been registered in China Clinical Trial Registration Center(registration code: ChiCTR1900022177, http://www.chictr.org.cn/).

Written informed consent was obtained from the participants for publication of this article and any accompanying tables/images.

The authors declare that there are no conflicts of interest.

No additional data are available.

The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

China

Tao He 0000-0001-8327-8697; Chan Liu 0000-0002-6210-4919; Zhi-Χia Lu 0000-0003-0943-4027; Li-Li Kong 0000-0003-3746-4477; Yan Li 0000-0003-4657-6630; Zhe Χu 0000-0002-3352-8309; Ya-Jing Dong 0000-0002-1689-4112; Wei Hao 0000-0002-0616-1812.

The design is based on assumption that the upper horizontal line is return line, under horizontal line is operating line.

Wu YΧJ

Filipodia

Wu YΧJ