Acute pancreatitis (AP) is an acute abdominal disease, characterized by a local pancreatic inflammatory response from an abnormal activation of pancreatic enzymes that have a digestive effect on the pancreas and surrounding organs¹. As one of the most prevalent gastrointestinal reasons for hospitalization in the United States, acute pancreatitis requires increasing attention as it continues to increase worldwide^2,3. In the past decade, the understanding of the pathophysiological mechanisms of acute pancreatitis has made significant strides^4,5,6. About 5%-10% of cases of acute pancreatitis are associated with severe organ dysfunction; this type of pancreatitis is defined as severe acute pancreatitis (SAP)⁷. Early Western medical treatment of AP generally consists of fluid therapy, analgesia, nutritional support, and treatment for the cause and early complications. However, Western medical treatment still lacks specific drugs for AP at this stage^8,9,10.

In traditional Chinese medicine (TCM), AP is referred to as "abdominal pain", "Pi Xin Tong", and "pancreatic fever". TCM enema therapy is one of the most used treatments in Chinese medicine, dating back to the honey decoction method from Zhang Zhong Jing's "treatise on cold pathogenic diseases" in the Han Dynasty¹¹. Its clinical efficacy is documented for the treatment of ulcerative colitis¹², hyperuricaemia¹³, acute radiation proctitis¹⁴, acute kidney injury¹⁵, and SARS-CoV-2 in the intestinal tract¹⁶.

In recent years, an enema with TCM (rhubarb^17,18, mirabilite¹⁹, and compound preparations such as Qingyi decoction²⁰ and Dachengqi decoction²¹) has been widely utilized in clinical and experimental studies of SAP. It has been shown to protect pancreatic function, reduce abdominal pain and abdominal distension, and delay disease progression^22,23. The 2021 Chinese guidelines for the diagnosis and treatment of AP include TCM enema²⁴. However, it is unclear how the TCM enema should be administered to SAP patients. Therefore, we present a protocol to perform the TCM enema, providing a potent method for investigating the components and mechanisms of ethnic drugs in the treatment of SAP patients²⁵.

The clinical protocol has been approved by the Administrative Committee of Department of Critical Care Medicine, Hospital of Chengdu University of Traditional Chinese Medicine (Record number: KY20221005). Experimental procedures were carried out in accordance with the guidelines of Hospital of Chengdu University of Traditional Chinese Medicine. The consent of the patients, who have signed an informed consent form, is required for the operation. The operator should understand the anatomy of the rectum before administering the enema and look at the anatomical annotations (see Figure 3).

1. Pre-therapy preparation of the operator

1. Include patients with principal symptoms (i.e., persistent epigastric pain).
2. Exclude patients with the following conditions: gastrointestinal bleeding, pregnancy, severe cardiovascular disease, arteriovenous tumor, hemiplegia, stroke, cardiopulmonary-cerebral insufficiency, severe colon ulcer or infarction, hernia, abdominal surgery, patients with intestinal adhesions, ileocectomy, megacolon disease and bleeding or perforation, patients with intestinal surgery, dialysis, patients with instinctive hypertension, catatonic heart disease, or severe hemorrhoids.
3. Exclude patients with a breakage of the perianal skin and a history of allergy to rhubarb.
4. Ensure that patients have no psychiatric disorders and can actively cooperate with the treatment.

2. Pre-therapy preparation of the patients

1. Have the patient eliminate both stool and urine before the operation.
2. Inform the patients that is it normal to experience localized sensations such as swelling, fullness, and mild pain.
3. Have patients promptly notify if defecation occurs or if there is discomfort.
   ​NOTE: The enema solution should be retained for more than 1 h, as the long retention time facilitates drug absorption²⁶.

3. Preparation of the decocted medicinal liquid

NOTE: The Hospital of Chengdu University of TCM supplied the raw rhubarb²⁷ (Rheum officinale Baill. DaHuang) (Figure 1).

1. Add 30 g of raw rhubarb and 200 mL of water to the automatic decoction and packaging machine.
2. Boil, and then simmer for 5 min.
3. Filter with a non-woven filter package (24 mm x 30 mm).
4. Remove residue with the non-woven filter package and cool down the remaining liquid to 37-39 °C.

4. Operational procedure

1. Check the patient's basic information (name, age, hospital number), verify the patient's condition, and re-evaluate them. Explain the process and advantages of an enema to the patient, making sure that they can fully understand and relax during it.
2. Regulate the room temperature (18-28 °C).
3. Prepare all necessary items (Figure 2 and Table of Materials). Check the expiration dates and bring them to the bedside.
4. Close all doors and windows. Ensure that the patients are not unnecessarily exposed and are kept warm.
5. Wash and dry hands, put on disposable gloves, and measure the temperature of the enema liquid using a thermometer beside the bed.
6. Assist the patient in assuming the left lateral decubitus position (if necessary, choose the right lateral decubitus position based on the condition). Fully expose the anus, place the center of the treatment sheet under the buttocks, and use a pillow to elevate the buttocks by 10 cm (Figure 3).
7. Lubricate the front end of the anal canal with paraffin oil, drain the paraffin oil from the anus, and expose the anus.
8. Adjust the temperature of the liquid medication to be equivalent to the patient's body temperature (37-39 °C) at a drip rate of 60-80 drops per minute, ensuring that the liquid level does not exceed 35 cm from the anus.
9. Close the stopper clip (part of the disposable enema kit) and pour the liquid into the hanging bag (part of the disposable enema kit).
10. Instruct the patient to open their mouth to breathe when inserting the anal canal, to relax the anus and facilitate the smooth insertion of the anal canal.
11. Insert the anus canal 30-35 cm²⁸ with the plastic hose (part of the disposable enema kit), open the stopper clip, and slowly drip the liquid (the dripping rate depends on the patient's condition) for 15 to 20 min.
    NOTE: If the plastic hose is blocked, close the stopper clip immediately and squeeze the pressurized bladder (part of the disposable enema kit) to unblock it.
12. During the infusion, constantly monitor and inquire about the patient's tolerance. Adjust the infusion rate in the event of discomfort or convenience and discontinue the infusion if necessary.
13. Perform general Tui na (place fingertips on the perianal skin to gently knead back and forth in a circular motion) to relax the muscles around the anus, before extubation of the plastic hose (Figure 2A)²⁹.
14. After administering the medication, clamp and remove the plastic hose from the anal canal.
    NOTE: The dosage for Chinese herbal enema should not exceed 200 mL.
15. Assist the patient in drying the perianal skin by gently rubbing the anus with gauze. Help the patient assume a comfortable lying position and elevate the buttocks.
    ​NOTE: If the patient has a sluggish pulse, a pale face, cold perspiration, severe abdominal pain, and palpitation, stop the operation immediately and contact a doctor.

5. Post-operation care

1. Have the patient lay in the left lateral position if they are still comfortable.
2. Have the patient rest. Advise them to use clean bedsheets, keep the anus dry and clean, and change the bedsheets promptly after fluid flows.
3. Observe fluid flow from the anus after the enema. Observethe shape, color, volume, and smell of the stool, to determine the success of the enema.
4. Advise the patient not to use excessive force to relieve stools, and inform healthcare staff promptly of any constipation.
5. Observe the patient's symptoms, temperature, blood pressure, pulse rate, heart rate, and respiration.

In this study, the patient was admitted because of repeated epigastric pain. According to the diagnostic criteria³⁰, the patient was diagnosed with SAP. After the patient was treated with this protocol, there was a noted therapeutic effect³¹.

Patient A, a female, 84 years old, was diagnosed for the first time on May 2, 2019. The patient complained of repeated epigastric distension and pain. The clinical tests showed that the serum amylase was 509 U/L (Reference values: 35-135 U/L), and that the urine amylase was 1,343 U/L (Reference values: 0-600 U/L). Physical examination showed that the abdomen was swollen, the total abdominal pressure was increased, and epigastric tenderness, rebound pain, and muscle tension were obvious.

After conventional Western medicine treatment (electrocardiogram monitoring, oxygen saturation monitoring, suction care, gastric tube preservation, continuous nasal cannula oxygen, fluid resuscitation, pancreatic suppression of secretion, parenteral nutrition support, electrolyte correction, and pain relief) and TCM enema treatment (using the liquid extract of raw rhubarb every 2 h), the patient noted that her upper abdomen pain was partially relieved on May 4, 2019. Clinical tests showed that the serum amylase dropped to 216 U/L, and that the urine amylase dropped to 526 U/L, adhering to the above therapy. On May 5, 2019, the above treatments were continued, and the patient noted that her upper abdomen pain was significantly relieved. Clinical tests showed that the serum amylase dropped further to 95 U/L, and that the urine amylase dropped to 81 U/L. On May 8, 2019, the TCM enema frequency changed to every 6 h. On May 15, 2019, the patient's symptoms and laboratory indicators improved significantly, and the patient was discharged.

Details on three patients are shown in Table 1. The clinical efficacy of control vs treatment patients is shown in Table 2.

Figure 1: Raw rhubarb in Chinese medicine. (A) The outer packaging of medicine at the hospital. (B) Sliced rhubarb. Please click here to view a larger version of this figure.

Figure 2: Experimental items. (A) Disposable enema device. (B) Thermometer. (C) Disposable medical kit. (D) Medical nursing pad. (E) Medical gauze pad. (F) Disposable gloves. (G) Care turning pillows. (H) Disposable treatment sheet. (I) Paraffin oil. (J) Raw rhubarb. (K) Automatic decoction and packaging machine. (L) Non-woven filter package. Please click here to view a larger version of this figure.

Figure 3: Schematic representation of the TCM enema therapy in SAP patients. The enema is performed by injecting raw rhubarb liquid into the patient's anus through a disposable enema device. After passing through the rectum, the liquid enters the large intestine at 30-35 cm, and plays a role in the treatment of SAP in the sigmoid colon. The figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license (HTTPS:// creativecommons.org/licenses/by/3.0/). Please click here to view a larger version of this figure.

Table 1: Representative results of enema therapy for the treatment of SAP patients. Reference values for abdominal pain: √-√√√√√. Reference values for serum amylase: 35-135 U/L. The frequency of enema: Q2H = every 2 h. Q6H = every 6 h. Q12H = every 12 h.

Table 2: Clinical efficacy of two groups in the hospital mentioned in the reference³². Control group: conventional therapy. Treatment group: conventional therapy + TCM enema. Compared with the experiment group, # p < 0.05.

AP is an inflammatory disease that can progress to SAP. According to numerous studies, SAP is a devastating disease linked with mortality ranging from less than 10% to as high as 85%, albeit with decreasing mortality in the recent decade³³. SAP seriously impacts patients' quality of life, and can even lead to death if not treated promptly and effectively. Aggressive and effective early treatment is of clinical importance³⁴.

Chinese herbal enemas have many advantages in treating SAP. There is complete absorption and high bioavailability as enemas are absorbed through the rectum, which not only prevents the destruction of drugs by gastric acid and digestive enzymes, but also significantly reduces the effect of the first-pass effect of the liver on drug efficacy. Rectal administration is simple, with few side effects, and is easy to dose.TCM enema therapy can be used in more patients with abdominal pain, constipation, and intestinal obstruction. The herbal medicines and their preparations can be used as enemas directly or after dissolution and dilution³⁵.

Rhubarb was chosen because it is inexpensive, easy to add, and clinically effective. Modern pharmacology research has found that rhubarb contains sennoside A, the anthrone glycoside of rhein, and the anthrone of rhein³⁶. Sennoside A has the functions of stimulating intestinal peristalsis, promoting intestinal secretion, enhancing intestinal tension, softening stool, improving intestinal paralysis, and promoting defecation, by relaxing the Oddi sphincter to promote the excretion of pancreatic juice and bile^37,38. It can effectively relieve abdominal pain and distension, and shorten the recovery time of serum amylase³⁶. TCM enema technology is underutilized, and it has the potential to cure a range of disorders, similar to other traditional Chinese medicine and therapy methods^39,40.

As for the limitations of the therapy, the following points are noted. As mentioned in the previous protocol, there are more contraindications. Enemas are an invasive operation and have the potential to cause embarrassment; therefore, operators need to ensure that they behave in a considerate and friendly manner, constantly communicating effectively with the patient. It may be beneficial to heat the enema to body temperature before administration, as the heat can irritate the rectal mucosa. Cold solutions should be avoided as they may cause abdominal cramping, leading to pain and discomfort. Providing comfort is essential. The operator should consider assessing the patient's vital signs before, during, and after the procedure. This is particularly important for individuals with neurological conditions and others who may be considered at risk.