Acupoint Application Combined with Acupressure as an Adjunctive Therapy for Chemotherapy-Induced Nausea and Vomiting

Acupoint application combined with acupressure-assisted treatment has a good effect on chemotherapy-induced nausea and vomiting and is more convenient and cost-effective.

Chemotherapy-induced nausea and vomiting (CINV) refers to the nausea and vomiting experienced by patients after the application of chemotherapy drugs, significantly affecting their quality of life and physical recovery, as well as increasing the pain of the patients. Basic medicine primarily focuses on acid suppression, gastric protection, and vomiting suppression, but there are still many patients with nausea and vomiting symptoms that cannot be alleviated. Traditional Chinese medicine (TCM) can effectively alleviate nausea and vomiting through acupoint stimulation and pressure, while also offering advantages such as simplicity, affordability, and fewer side effects. The aim of this article is to introduce the method of using acupoint application combined with acupressure as an adjunctive therapy for CINV, using the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool (MAT) tablet scale as a questionnaire. The article details aspects such as acupoint selection, production, and the use of acupoint application, massage techniques, and operating procedures, all with the goal of ensuring the safety and efficacy of acupoint application combined with acupressure as an adjuvant therapy, thereby improving patients' clinical symptoms and quality of life.

Chemotherapy, as one of the important methods for treating cancer, treats tumors while also imposing various side effects on patients. Chemotherapy-Induced Nausea and Vomiting (CINV) refers to the symptoms of nausea and vomiting that occur after a patient receives chemotherapy drugs. Nausea is a subjective sensation of uneasiness in the epigastrium or throat, often accompanied by an impending sense of vomiting. Vomiting involves the ejection of stomach contents through the mouth. Both nausea and vomiting can happen simultaneously or independently, with nausea being more frequently experienced than vomiting among chemotherapy patients¹. Affecting patients' ability to eat, reducing their quality of life, and making it even more challenging for cancer patients to adhere to treatments, CINV has become one of the most feared side effects among those undergoing chemotherapy. Modern medicine often employs acid-suppressing, gastric protection, and antiemetic medications, such as ranitidine, metoclopramide, and ondansetron, to alleviate discomfort. Despite these drugs, over 30% of cancer patients undergoing chemotherapy still experience CINV, and nausea symptoms are as high as 60%-70%². Hence, the pressing issue at hand is to effectively alleviate CINV and enhance supportive cancer treatments.

Acupoint application combined with acupressure is a traditional Chinese medical operation. In TCM theory, acupoints are locations on the body's surface where qi and blood converge. Stimulating these points influences the flow of qi and blood, thus achieving the purpose of treatment. In traditional Chinese medicine, Cun is the unit of length for measuring human body parts. The measurement methods of cun often include the standard body Cun and Body Cun. In this operation, different acupoints adopt different measurement methods. According to the preferred Body Cun method, the width of the thumb joint of the patient is 1 cun. The total width of the index, middle, ring, and little fingers, stretched side by side, is 3 cun; the middle section of the middle finger is taken as the standard. The standard body cun of an average male is ~2.31 cm. Acupoint application refers to grinding herbs like ginger, clove, sandalwood, persimmon kernel, and mugwort into a paste, which is then applied to specific acupoints such as Shenque (CV8, located in the upper abdomen, at the center of the navel); ZuSanLi (ST36, found on the inner side of the lower leg, 3 cun below DuBi (ST35), along the line connecting DuBi (ST35) and Jiaxi (ST41)); Neiguan (PC6, situated on the anterior aspect of the forearm, 2 cun above the wrist crease, between the tendons of the palmaris longus and the radial flexor of the wrist); Weishu (BL21, on the back, 1.5 cun lateral to the midline, directly below the 12th thoracic vertebra); and Geshu (BL17, on the back, 1.5 cun lateral to the midline, directly below the 7th thoracic vertebra). By being absorbed through the skin on specific areas of the body, acupoint application aims to enhance the circulation of qi and blood, thereby alleviating the symptoms of CINV.

Research indicates that ginger contains bioactive compounds that bind to 5-HT3 receptors, relieving nausea and vomiting³. Regarding anticipatory CINV, the application of acupressure, where consistent rhythmic pressure is applied to specific points on the body, can also alleviate symptoms of nausea and vomiting⁴. According to the expert consensus released by the Chinese Society of Anesthesiology, which integrates traditional Chinese and Western medicine, the primary acupoints for treating postoperative nausea and vomiting are Zusanli and Neiguan⁵. Gently massage the abdomen in a clockwise direction with the palm, synchronizing with the breath, to alleviate the effect of stomach qi upflushing and stop nausea. Research indicates that acupressure also helps divert attention and relieve patients' anxious feelings, demonstrating excellent intervention for nausea⁶. Furthermore, for patients who have undergone multiple chemotherapy sessions, environmental triggers present during previous episodes of CINV, such as visual, auditory, or olfactory cues, can become associated with nausea and vomiting in their minds. Subsequent exposure to the same stimulus environment elicits a conditioned reflex of nausea and vomiting. The operation of acupoint application and acupressure, before chemotherapy, can serve as psychological comfort, reducing or even preventing this conditioned response.

A demonstration of acupoint application combined with acupressure for treating nausea and vomiting in a patient receiving chemotherapy is presented in this article. To evaluate the effectiveness and safety of this method, the study used clinical randomized controlled trial data. Efficacy was based on the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool (MAT) scale⁷ form completed after the patient's treatment..

Trial data were collected from a randomized controlled experiment conducted on chemotherapy patients in the Oncology Department of Chengdu First People's Hospital. This trial follows the Helsinki Declaration and was approved by the Oncology Department of Chengdu First People's Hospital, with proper documentation within the department. Patients received relevant trial information and signed informed consent was collected prior to trial commencement.

1. Patient selection

1. Set the inclusion criteria to be confirmed malignant tumor diagnosis, no contraindications to chemotherapy and willingness to undergo it, the absence of nausea and vomiting symptoms 48 h prior to chemotherapy, and an expected survival period of more than 3 months.
2. Set the exclusion criteria to be severe coexisting conditions (such as hypertension, diabetes, or coronary heart disease); nausea and vomiting due to neurological disorders, gastrointestinal diseases, or increased intracranial pressure; significant liver or kidney function issues; and participation in other clinical trials.
3. Terminate the study for a patient if that patient is unwilling to continue with the study, has allergic reactions to the drugs during the trial, and whose condition worsens and prevents further participation.
4. Once selected, assign the patients to a control group (six patients in this study) receiving standard treatment (here, ondansentron and dexamethasone intravenously)⁸ before chemotherapy and the treatment group (six patients here) to be given acupoint application 1 day before the chemotherapy and acupressure performed before and 30 min after chemotherapy.

2. Preparation for the operation

1. Material preparation
   1. Place 100 g of Chinese herbs (20 g of fresh rhizome of ginger, 20 g of cloves [dried flower buds], 20 g of nutmeg [dried ripe fruit], 20 g of Kaki calyx [dried calyx of Diospyros kaki Thunb], and 20 g of Aucklandia lappa Decne[dried roots]) in the grinder machine to grind them in advance and seal the paste in a medical bent plate for later use.
   2. Take 50 g of the Chinese herbal powder and use 50 mL of saline and 50 g of medical Vaseline to make a paste of the Chinese herbal powder.
   3. Take a thumb-sized amount of the Chinese herbal paste from the medical bent plate, make it into a shape similar to a ball (diameter of about 1 cm), and apply it to the breathable adhesive application.
   4. Finally, place the prepared acupoint applications in a medical bowl for later use.
      NOTE: Approximately five patches will suffice.
2. Operator and patient preparation
   1. Confirm that the operating environment is safe and the items are complete.
   2. Instruct the patient to empty the bladder in advance.
      NOTE: Do not operate on an empty or full stomach.
   3. Confirm the patient's information, respect their privacy, and evaluate the local skin of the patient's acupoint to ensure that the skin around the selected points is free of lesions or damage.
   4. Inform the patient or their family about the purpose of the treatment, its contents, and possible adverse reactions.
   5. Assist the patient in lying down comfortably on the treatment bed in a supine position.

3. Operation steps

1. Instruct the patient to sit down and locate the intersection of 3 cun below the concave point of the patient's lateral knee joint and 1 cun from the anterior edge of the tibia; mark this position of the intersection as Zusanli (ZuSanLi ST36, Figure 1).
2. Instruct the patient to lie in a horizontal position, with both legs straight and flat. Mark the patient's center of the navel as Shenque (ShenQue CV8, Figure 2).
3. Instruct the patient to sit, stretch the arm, and hold the fist, slightly bending the wrist. Record 2 cun (~4.6 cm) from the midpoint of the wrist stripes as Neiguan in the forearm area (Neiguan PC6, Figure 3).
   NOTE: Neiguan (PC6) is situated on the anterior aspect of the forearm, 2 cun above the wrist stripes, between the tendons of the palmaris longus and the radial flexor of the wrist.
4. Disinfect both hands, place the thumb thread surface at the patient's Neiguan (PC6), and expand the remaining four fingers in a relative position to balance the force.
5. Bend the wrist joint 40-60°, use the thumb pulp to actively exert force, and press the acupoint by continuously extending and flexing the first finger joint of the thumb.
   NOTE: The frequency is 80-120 times/min, 5-6 min each time until the patient has a sense of soreness.
6. Grasp the fist, using the back of the first knuckle of the index finger as the force point. Press and knead the Zusanli (ST36) acupoint. Press and knead 20x clockwise, and then, press and knead 20x counterclockwise.
   NOTE: The frequency is 50-60 times/min, each lasting 3-5 min until the patient has a sense of acid bloating.
7. Wear the medical rubber glove, soak the cotton swabs in 75% ethyl alcohol, and rub the bilateral Zusanli (ST36) and Shenque (CV8) acupoints with the cotton.
8. Fix the breathable adhesive acupoint applications containing the Chinese herbal paste on the patient's Shenque (ST36) point and bilateral Zusanli (CV8), clean up the excess paste around the acupoint, and assist the patient in dressing. Put the applications on once a day and leave them for 6-8 h. To avoid falling off of the applications, instruct the patient not to do intense exercise. If the patient's skin appears red or the patient experiences blisters or itching, consider drug allergy, remove the acupoint application in time, and clean the skin with normal saline to keep it dry.
9. After the completion of the operation, pick up the remaining items, sort the medical waste, and assist the patient in restoring the position.

4. Assessment of efficacy utilizing the MAT tool

NOTE: The assessment of efficacy utilized the Brief Assessment Scale for Chemotherapy-Induced Nausea and Vomiting (CINV) developed by the Multinational Association for Supportive Care in Cancer (MASCC). This scale (Supplemental File 1) consists of eight items, with the first four items addressing acute nausea and vomiting and the last four items focusing on delayed nausea and vomiting. Items 4 and 8 use a quantitative form of 0 to 10 to assess the subjective symptoms of nausea.

1. Fill the upper part of the MAT scale (items 1-4) within 24 h after chemotherapy and the lower part after 24 h after chemotherapy, and grade the degree of nausea and vomiting according to the scores and WTO evaluation indicators.
   1. Define grade 0 as no nausea (a score of 0-1) or vomiting; grade I as mild nausea (a score of 2-4) without vomiting; grade II as mild nausea and vomiting (<2x over 24 h); grade III as moderate nausea (a score of 5-7) and vomiting (<3-5x over 24 h); grade IV as severe nausea (a score of 8-10) and vomiting (>5x over 24 h).
2. Collect data from the MAT scale scores of the treatment and control groups. Consider grades 0-I as complete remission (markedly effective treatment), grade II as partial remission (effective), and grades III-IV as no remission (ineffective). Use analysis software of choice and chi-square test for treatment effectiveness and independent sample t-test for the nausea scores.

A clinical trial was conducted involving 12 patients receiving chemotherapy at the First People's Hospital of Chengdu for oncology treatments between January and February 2024. A total of 12 patients receiving chemotherapy were included in this study, of which 8 were male, accounting for 66.6%, and 4 were female, accounting for 33.3%. Of the 12 patients receiving chemotherapy, six were in the control group and six in the treatment group. The statistical analysis of weight and height between the treatment group and the control group showed no significant significance (Table 1). After the end of one chemotherapy cycle, CINV occurring within the first 24 h has been defined as the acute phase and CINV occurring more than 24 h later is defined as the delayed phase. In terms of overall marked effectiveness (see protocol step 4.2), during the acute phase of CINV, the control group showed a markedly effective rate of 66.7%, while the treatment group had a markedly effective rate of 83.3%, as seen in Table 2. Though there was a difference between the two groups, it was not statistically significant (P > 0.05). During the delayed phase, the control group's markedly effective rate was 16.7%, compared to the treatment group's 83.3%, as shown in Table 3. This difference was statistically significant (P < 0.05), indicating that the treatment group had higher effectiveness rates than the control group both acutely and in the delayed phase.

In terms of nausea severity scoring, during the acute phase, the mean scores for both groups differed but without statistical significance (P> 0.05, see Table 4). However, during the delayed phase, the control group's nausea severity score (4.17 ± 1.16) was higher than the treatment group's (2.67 ± 1.03), with a statistically significant difference (P< 0.05, see Table 5). These results suggest that the combination of acupressure and acupoint application as an adjunct treatment for CINV is more effective than normal treatment. It effectively reduces the recurrence frequency of CINV during the delayed phase, particularly demonstrating remarkable efficacy in alleviating nausea severity, thereby improving the patient's quality of life.

Figure 1: Location map of Zusanli acupoint (ST36). The intersection of 3 cun below the concave point of the patient 's lateral knee joint and 1 cun from the anterior edge of the tibia is marked as Zusanli (ST36). The total width of the index, middle, ring, and little fingers, stretched side by side, with the middle section of the middle finger taken as the standard, is 3 cun. Please click here to view a larger version of this figure.

Figure 2: Location map of abdominal Shenque acupoint (RN8). The Shenque acupoint (RN8) is in the abdominal umbilical, at the center of the navel. Please click here to view a larger version of this figure.

Figure 3: Location map of Neiguan (PC6) acupoint. Stretch the arm and hold the fist, slightly bend the wrist, and the two cun of the wrist stripes are recorded as Neiguan (PC6). Please click here to view a larger version of this figure.

Table 1: Baseline analysis of height and weight of patients. The average height of the control group is 166.33 ± 7.09 cm and of the treatment group is 163.83 ± 6.08 cm. The average weight of the control group is 51.50 ± 3.83 kg and of the treatment group is 49.3 3 ± 4.08 kg. P (Height) = 0.527 > 0.05, P (Weight) = 0.366 > 0.05.

Table 2: Evaluation of markedly effective acute phase treatment. Grades 0- were considered complete remission (markedly effective), while grade was considered partial remission (effective).

Table 3: Evaluation of markedly effective delayed phase. Grades 0- were considered complete remission (markedly effective), while grade was considered partial remission (effective).

Table 4: Acute phase nausea intensity scoring evaluation. The mean scores of nausea were 0.17 ± 0.40 in the acute phase of the treatment group and 1.33 ± 1.50 in the acute phase of the control group, but there was no statistical significance (P = 0.097 > 0.05).

Table 5: Delayed phase nausea intensity scoring evaluation. The mean scores of nausea were 2.67 ± 1.03 in the delayed phase of the treatment group and 4.17 ± 1.16 in the delayed phase of the control group; there was a statistically significant difference (P = 0.04 < 0.05).

Supplemental File 1: The Multinational Association of Supportive Care in Cancer Antiemesis Tool. Please click here to download this File.

Numerous cancer patients, such as those with breast cancer, lung cancer, prostate cancer, or hematological malignancies, commonly endure nausea and vomiting during chemotherapy. This unpleasant experience can lead to decreased appetite, inadequate nutrition intake, and poor physical condition, negatively impacting the overall treatment outcome. It also reduces patient adherence to therapy and fosters fear towards chemotherapy⁹. In over three decades of research, it has been found that the 5-HT3 receptor plays a crucial role during the acute phase of chemotherapy-induced nausea and vomiting¹⁰. Contemporary medical research suggests that after exposure to radiation or cell-toxic medications, enterochromaffin cells within the small intestinal mucosa release serotonin (5-HT). This released serotonin acts through 5-HT3 receptors, stimulating vagal afferent neurons, and ultimately leading to vomiting triggered via the chemoreceptor trigger zone (CTZ) within the spinal cord's posterior region. Additionally, Substance P, a neuropeptide, functions as a neurotransmitter or neuromodulator in both central and peripheral nervous systems by preferentially binding to NK-1 receptors. It is also implicated as a relevant neurotransmitter in chemotherapy-induced nausea and vomiting (CINV)^11,12,13.

Currently, frequently utilized antiemetic medications include 5-hydroxytryptamine type 3 receptor antagonists (5-HT3 RA), corticosteroids, and Neuropeptide 1 receptor antagonists. Ondansetron, as a first-generation 5-HT3 RA, can achieve an acute CINV control rate of 52.9%-68.8%¹⁴. Yet, it is not effective in the control of delayed CINV¹⁵. If the correct antiemetic treatment is not received, 70%-80% of patients undergoing chemotherapy will experience nausea and vomiting,Among patients receiving antiemetic therapy, over 30% of them still experience CINV, with nausea reaching rates as high as 60%-70%¹⁶. The common side effects of these medications include mild headache, transient elevations in liver enzyme levels, and constipation, which is also one of the most unpleasant and adverse events affecting treatment and the quality of life. Consequently, researching effective ways to alleviate nausea, reduce vomiting, and deal with the side effects of anti-nausea and vomiting drugs for optimal therapy is an important issue.

Acupoint application is a characteristic therapeutic operation in traditional Chinese medicine, which was first recorded in the ancient medical text "Fifty-Two Disease Treatments." According to TCM theory, vomiting is attributed to the upward rebellious movement of stomach qi, and the disease is located in the spleen and stomach. In managing CINV, TCM emphasizes individualized treatment based on the patient's constitution and symptom presentation, though the ultimate focus is still on regulating the upward movement of stomach qi. The therapy primarily aims at harmonizing the stomach qi¹⁷ Herbal medicines are formulated into a paste and applied to acupoints, allowing their effects to be absorbed through the skin. This approach circumvents the issue of oral medication causing vomiting in chemotherapy patients, improving compliance, and providing a longer-lasting effect that is convenient for replacement.

Li's team¹⁸, through a meta-analysis, found significant efficacy of herbal acupoint application in treating CINV in malignant tumors. Among the acupoint selections, Neiguan combined with ZuSanli was most frequently used, while other combinations might involve points like Shenque and Zhongwan. When looking for points to ensure the accuracy of acupuncture points, the operator can gently wipe and apply pressure with their fingers on these points, ensuring a level of pressure that causes mild soreness, numbness, or tingling, to confirm accurate acupoint selection. In the operation of acupoint application, the following points must be noted. First, the duration may vary according to the patient's condition; if skin swelling, itching, redness, or even ulceration occurs, remove the patch earlier. Instruct the patient to avoid strenuous activities to prevent the patch from falling off. If it detaches prematurely, inform the operator for reapplication. Third, maintain the dressing and local skin dryness avoiding seepage. Finally, if there is already a patch applied to the Zusanli point, acupressure can be performed during the intervals of replacing the patch. The therapeutic effect is considered achieved when the patient experiences soreness, numbness, fullness, or pain at the acupoint. The procedure is simple enough that patients can be instructed to self-administer it. If adverse skin reactions occur, such as redness, swelling, blisters, or itching, drug allergy should be considered. Application should then be discontinued, and patients should be advised to keep their skin dry, avoid scratching, and observe for 3 days.

In Traditional Chinese Medicine, the Zusanli point is considered a converging point of the Stomach Meridian of Foot-Yangming and the lower connecting point for the stomach organ. Acupoints, referred to as 'He points,' are locations along meridians where the abundant qi converges and connects with the internal organs. Traditional Chinese medicine meridian theory states that the Stomach Meridian of Foot-Yangming is the most vigorous with respect to qi and blood between 7 AM and 9 AM, and it is also the best time to operate acupoint application and acupressure. Ancient texts on acupuncture, such as "The Classic of Needles," state that "Patients with gastropathy often experience meteorism, stomach pain, flank pain, poor appetite, and other symptoms. During treatment, the Zusanli point can be selected for therapy." Hence, Zusanli is commonly utilized to treat stomachache, bloating, abdominal pain, nausea, vomiting, constipation, or diarrhea associated with gastrointestinal disorders.

Research has suggested that stimulating this acupoint might regulate the digestive system by altering brain-gut peptide hormones, specifically Cholecystokinin (CCK) and Ghrelin, which play crucial roles in this process¹⁹. The regulation of the gastrointestinal tract by CCK mainly involves relaxing the proximal stomach, inhibiting gastric antral movement, and delaying gastric emptying²⁰. The Gasco team²¹ has found that Ghrelin possesses appetite-stimulating properties, enhances gastric acid secretion, and exhibits motility effects similar to Motilin, promoting stomach emptying and increasing gastrointestinal activity. It also works in synergy with neuropeptides and orexins to enhance food intake. Furthermore, needling the Zusanli acupoint regulates Endothelin and Gastrin in the brain-gut peptide system, improving blood flow to the gastric mucosa and modulating gastric acid secretion, thus exerting a protective effect against gastric mucosal injury¹⁹. Pressing on the Neiguan point can alleviate symptoms such as palpitations, nausea, and vomiting, as well as tachycardia, making it useful for anti-emetic treatments. Modern medical research has confirmed that effective stimulation of the Neiguan point activates the patient's adrenergic and noradrenergic fibers, altering the transmission of serotonin within the body, and ultimately resulting in a reduction in the incidence of postoperative nausea and vomiting.

The Shenque Point is one of the acupoints on the Ren Meridian and according to traditional Chinese medicine theory, it is believed to have the function of supporting vitality and stabilizing collapse, as well as improving gastrointestinal dysfunction and promoting diuresis to alleviate edema. Miao²² believes that acupoint application on the Shenque acupoint has a therapeutic effect in promoting the secretion of gastrin. The Shenque point, located in the center of the navel, is the last area of the abdomen to close and has relatively thin skin, which facilitates drug absorption, allowing for better absorption of medications. Chen²³ indicates that the bioavailability of medications administered through the umbilical region is 1 to 6 times higher than when administered on the forearm, making it highly suitable for drug delivery.

In terms of acupoint selection, apart from Zusanli, Shenque, and Neiguan points, there are also combinations involving other acupoints such as Zhongwan (RN12) and Yongquan (KI1). In terms of herbal combinations, in addition to the above herbs, the herbal combination can be selected according to the analysis of the specific symptoms of patients and under the guidance of TCM syndrome differentiation and treatment. Following this approach, researchers like Shen²⁴ have chosen to use 15 g of Codonopsis, 15 g of White Atractylodes, 10 g of Tangerine Peel, 10 g of Costus Root, 10 g of Pinellia, 6 g of Fresh Ginger, and 3 g of Euodia ruticarpa. Liu²⁵, in contrast, has opted for 15 g of Perilla Stem, 10 g of Fried Magnolia Bark, 10 g of Processed Atractylodes Rhizome, 5 g of Agarwood, and 3 g of Clove. These herbs are mixed with honey, and their application is tailored according to the patient's symptoms differentiation to enhance therapeutic effectiveness.

In the treatment of CINV, while conventional medicine can alleviate symptoms, its efficacy is not high enough, and the issue of side effects cannot be overlooked. In contrast, the combination of acupoint application and acupressure in Traditional Chinese Medicine demonstrates remarkable advantages. This non-pharmacological approach not only yields significant effects but also enhances the effectiveness of treatment, reduces nausea severity, and minimizes potential side effects and drug resistance associated with medication. The advantage of the MAT scale, compared to others, is its ease of use, longer evaluation period, and suitability for caregiver assessments.

Although current research data are insufficient, preliminary trial results suggest that acupoint application combined with acupressure has some therapeutic potential in adjunctive treatment for CINV. As research progresses, this therapy is expected to be an effective management tool for these symptoms in chemotherapy patients. However, due to the limited sample size in current trials, the study outcomes are not yet sufficiently representative. Future studies should expand the sample size and delve deeper into the specific mechanisms by which TCM interventions function in treating chemotherapy-induced nausea and vomiting, aiming to provide more robust evidence for clinical practice.

The authors have no conflicts of interest to declare.

We acknowledge the financial support from the 'Scholar of XingLin' Discipline Talent Research Enhancement Program of Chengdu University of Traditional Chinese Medicine (Grant No. XKTD2022014).