Application of mirabilite in gastrointestinal surgery: A randomized controlled trial

Abstract

BACKGROUND

Gastrointestinal surgeries often require auxiliary incisions, which may lead to postoperative complications such as surgical site infections (SSIs) and fat liquefaction of the abdominal wall. This inevitably leads to prolonged hospital stays and increased treatment costs. External application of mirabilite, believed to work through its hypertonic property that draws out edema fluid and modulates local inflammation, helps reduce swelling in the surgical area.

AIM

To prospectively evaluate the effects of topical mirabilite application on postoperative complications and short-term recovery in patients undergoing gastrointestinal surgery.

METHODS

This prospective randomized controlled trial included gastrointestinal surgery patients. Eligible participants were randomly allocated to two groups (1:1 ratio). The mirabilite group received topical mirabilite to the abdomen combined with routine wound dressing, while the control group received routine wound dressing only. The primary outcomes were the incidence of SSI and the time to first flatus. Secondary outcomes included postoperative inflammatory markers (C-reactive protein), pain scores, drainage volume, length of hospital stay, and other postoperative complications.

RESULTS

From October 2023 to April 2024, 332 eligible patients were recruited, with 301 patients completing the study and undergoing final analysis. The clinicopathological characteristics were well balanced between the two groups. The mirabilite group had a lower incidence of SSI (P = 0.042). Compared to the control group, the mirabilite group had a significantly earlier time to first flatus (38 hours vs 57 hours, P < 0.001), shorter postoperative hospital stays (8.5 days vs 9.0 days, P = 0.028), lower C-reactive protein levels (P = 0.038), lower pain scores over 3 days (P = 0.027), significantly lower drainage volume within 7 days (P < 0.01).

CONCLUSION

The findings suggest that topical application of mirabilite may reduce the incidence of wound complications. mirabilite appears to facilitate the recovery of gastrointestinal function in patients undergoing gastrointestinal surgery.

Key Words: Mirabilite; Gastrointestinal surgery; Surgical site infection; Postoperative gastrointestinal dysfunction; C-reactive protein

Core Tip: This randomized controlled trial provides robust evidence that the topical application of mirabilite, a traditional external therapy, is a simple yet effective adjunct to standard postoperative care in gastrointestinal surgery. The treatment demonstrates multifaceted benefits: It significantly accelerates recovery of gastrointestinal function, reduces postoperative pain and systemic inflammation, decreases drainage volume, and lowers the incidence of surgical site infections. These clinically meaningful outcomes led to a shorter hospital stay, highlighting mirabilite’s potential to improve patient recovery and optimize healthcare efficiency. Mirabilite application represents a safe, practical, and valuable non-invasive strategy to enhance short-term surgical recovery.

INTRODUCTION

Patients undergoing gastrointestinal surgery frequently encounter complications, particularly surgical site infection (SSI) and postoperative gastrointestinal dysfunction (POGD). SSIs are defined as infections that occur within 30 days after surgery, involving the incision site or surrounding tissues[1]. These infections can manifest as superficial incisions (affecting the skin at the incision), deep incisions (affecting deeper layers such as muscles), or more severe organ/space infections, where the infection extends into body cavities or internal organs[2]. SSIs are one of the most common hospital-acquired infections, and due to the unique nature of gastrointestinal surgeries, where the surgical area is exposed to intestinal bacteria, these procedures are typically classified as class II incisions (clean-contaminated wounds)[1,3,4]. The infection rates in gastrointestinal surgeries are significantly higher than in other surgical procedures[4,5]. Despite the widespread use of laparoscopic techniques and perioperative antibiotics, which have contributed to reducing SSI rates[6], SSIs remain a prevalent postoperative complication in gastrointestinal surgeries.

POGD is a common complication following abdominal surgery. Its occurrence is related to various factors, such as the type of surgery and trauma, anesthetic drugs, and inflammatory response, among others[7]. POGD is commonly characterized by symptoms such as delayed bowel motility, nausea, vomiting, abdominal distension, and constipation following surgery[8]. Traditional treatments for POGD, such as nasogastric decompression, prokinetic agents, and delaying the early intake of liquids and food, have shown limited effectiveness in significantly accelerating gastrointestinal recovery[9,10]. Thus, it is imperative to explore more effective and convenient treatment modalities and postoperative recovery strategies to address this clinical challenge.

Mirabilite, also known as sodium sulfate decahydrate, is a naturally occurring sulfate mineral widely used in traditional Chinese medicine. Mirabilite is mined from mineral deposits and is not plant-based. For medicinal use, it is typically purified to meet pharmacopeia standards[11]. Mirabilite’s main actions include promoting bowel movement, reducing dryness, softening hardened masses, clearing heat, and reducing swelling[11]. Its pharmacological action is primarily exerted through external application, leveraging its high osmotic pressure to reduce edema at surgical sites and in the gastrointestinal tract, thereby reducing localized swelling, improving circulation, and facilitating the absorption of inflammatory factors[12]. Additionally, mirabilite alleviates local inflammation by reducing the infiltration of inflammatory cells and the proliferation of fibrous tissue. It also modulates inflammatory cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor-α, thereby reducing gastrointestinal inflammation[13]. As a result, it decreases the incidence of SSI and promotes gastrointestinal function recovery[14].

No randomized controlled clinical studies, in China or internationally, have analyzed the safety, efficacy, and short-term outcomes of mirabilite external application on the abdomen vs standard care without external application. Therefore, this study aimed to evaluate the clinical efficacy and safety of mirabilite external application in preventing postoperative wound complications (such as SSI and delayed wound healing) and promoting gastrointestinal function recovery in patients undergoing gastrointestinal surgery.

MATERIALS AND METHODS

Study design

This prospective, open-label, single-center, randomized controlled trial was designed to evaluate the efficacy and safety of mirabilite application in patients undergoing gastrointestinal surgery, and to compare it with standard care. The study was conducted at the First Affiliated Hospital of Nanchang University and was approved by the Institutional Review Board of the First Affiliated Hospital of Nanchang University. This trial was registered at ClinicalTrials.gov (No. NCT06696729). All methods were carried out in accordance with relevant guidelines and regulations, including the Declaration of Helsinki. Informed consent was obtained from all participants, or their legal guardians, for personal and medical data collection prior to study enrolment. The results comply with the Consolidated Standards of Reporting Trials 2010 guidelines.

Participants

Between October 2023 and April 2024, we recruited 332 patients requiring gastrointestinal surgery (Figure 1).

Figure 1 Subject flow diagram. ASA: American Society of Anesthesiologists.

Inclusion criteria: (1) Patients who had undergone laparoscopic-assisted gastrointestinal surgery (distal gastrectomy, total gastrectomy, right hemicolectomy, left hemicolectomy, sigmoid colectomy, or low anterior resection); (2) Aged 18-80 years; and (3) Signed the informed consent forms.

Exclusion criteria: (1) Patients who required unplanned surgery for any reason within 30 days postoperatively; (2) Presence of emergency conditions, such as bowel obstruction or gastrointestinal bleeding; (3) Severe mental illness; (4) Undergoing surgical interventions for advanced tumors (including palliative or bypass surgeries); (5) American Society of Anesthesiologists (ASA) classification > 3; (6) Requested to withdraw from the study for any reason after enrollment; (7) Poor compliance or mirabilite use for < 3 days; or (8) Discharged unexpectedly.

Randomization and blinding

Participants were randomly assigned to groups using a computer-generated randomization table. Specifically, a table with two group allocations (mirabilite group and control group) was generated. Patients were subsequently assigned to groups according to the order of their surgeries, following the sequence outlined in the randomization table.

Due to the distinctive characteristics of external application of mirabilite, an open-label design was unavoidable in this study. Consequently, both the operating surgeons and patients were aware of the group assignments following intervention initiation. However, to minimize assessment bias, data collectors and data analysts remained blinded to the treatment allocation throughout the entire study period.

Intervention

Standardized postoperative wound care protocol: For all patients in both groups, the abdominal incision was immediately covered with a sterile, non-adherent dressing after surgery. This primary dressing was then overlaid with three layers of standard sterile gauze pads and secured with hypoallergenic surgical tape. Dressings were routinely changed on the first postoperative day and every 48 hours thereafter, or immediately if the dressing became contaminated, saturated, or displaced. During each change, the incision was inspected, and the skin was cleansed using sterile normal saline.

Mirabilite group: Starting from postoperative day 1, 500 g of granulated mirabilite was applied. The mirabilite was wrapped in a double layer of gauze and placed on top of the sterile dressing covering the patient’s abdominal incision (using either four layers of sterile gauze or one sterile dressing). The gauze bag was then secured with an abdominal binder. When the gauze bag became damp and hardened, it was promptly replaced to ensure continuous external application and effectiveness of the treatment.

Control group: Patients in the control group received standard postoperative care without the use of mirabilite.

Outcomes

The primary endpoints of the study included recovery of gastrointestinal function and the incidence of SSI. Secondary outcomes included postoperative inflammatory markers [C-reactive protein (CRP)], pain scores, drainage volume, length of hospital stay, and other postoperative complications.

Baseline characteristics of the patients included age, gender, body mass index (BMI, kg/m²), ASA classification, and surgical site. The surgical parameters recorded were operative time, intraoperative blood loss, postoperative drainage volume, and incision length. Time to first flatus was taken to indicate gastrointestinal function recovery. CRP was measured on postoperative day 1, day 4, and day 7 as an inflammatory marker. Prognostic outcomes included the probability of postoperative complications and postoperative hospital stay. Visual Analog Scale (VAS) pain scores were recorded on postoperative days 1-3 using a 10-cm VAS ranging from 0 (no pain) to 10 (extreme pain). Post-surgery, each patient was assessed at the same time each morning by trained nursing staff to ensure standardized scoring. Additionally, patients’ albumin levels on postoperative day 1 and day 4 were collected.

Sample size

Based on previous research, the incidence of SSI in the control group was estimated to be 16.3%[15]. The application of mirabilite plaster during post-cesarean recovery can reduce the incidence of localized incision swelling and redness by 10%[14]. It was assumed that the incidence of SSI in the mirabilite group was 5%. Setting α = 0.05 for a two-sided test and β = 0.20, the required sample size per group was calculated using G*Power 3.1.9.7 software (Heinrich Heine University, Düsseldorf, Germany) to be 118 participants. Considering an estimated dropout rate of 20%, each group was to include 148 patients.

Statistical analysis

All statistical analyses were performed using SPSS version 27.0 (IBM Corp., Armonk, NY, United States). First, data normality was assessed using the Kolmogorov-Smirnov test. Data with a normal distribution were expressed as mean ± SD, and non-normally distributed data as median (interquartile range). Independent-samples t-tests or Mann-Whitney U tests were used for comparisons. Categorical data were analyzed using χ² tests or Fisher’s exact tests and expressed as n (%). P < 0.05 were considered statistically significant.

RESULTS

Clinical baseline characteristics

From October 2023 to April 2024, 332 patients were assessed for eligibility and enrolled. Exclusions comprised 15 patients who underwent emergency surgery (8 with obstructive colorectal cancer, 3 with perforated gastric cancer, 2 with hemorrhagic colorectal cancer, and 2 with hemorrhagic gastric cancer) and 1 with an ASA score > 3. Thus, 316 patients underwent randomization, with 157 allocated to the mirabilite group and 159 to the control group. In the mirabilite group, three cases were excluded due to open-and-close surgery, and four because the duration of mirabilite use was < 3 days. In the control group, two cases were excluded due to unplanned reoperation within 30 days, one case due to open-and-close surgery, and five cases due to withdrawal of informed consent. Consequently, 301 cases (150 in the mirabilite group and 151 in the control group) underwent final analysis (Figure 1). The two groups showed comparable gender, age, BMI, surgical site (stomach, right colon, left colon, sigmoid colon, or rectum), comorbidities, and ASA classification at baseline, with no statistically significant differences (Table 1).

Table 1 Comparison of baseline data between the mirabilite and control groups, n (%)/mean ± SD.

Variable	Mirabilite group	Control group	P value
Gender			0.688
Male	92 (30.56)	97 (32.23)
Female	58 (19.27)	54 (17.94)
Age, years	60.82 ± 10.49	61.52 ± 10.19	0.620
BMI, kg/m2	22.87 ± 2.92	22.80 ± 2.95	0.706
ASA			0.577
II	13 (4.32)	17 (5.64)
III	137 (45.51)	134 (44.52)
Comorbidities
Diabetes mellitus	16 (10.67)	18 (11.92)	0.731
Chronic lung disease	11 (7.33)	10 (6.62)	0.783
Hypertension	22 (14.67)	25 (16.56)	0.654
Coronary heart disease	7 (4.67)	6 (3.97)	0.741
Preoperative hypoalbuminemia (< 35 g/L)	14 (9.33)	18 (11.92)	0.467
Surgical site			0.426
Stomach	54 (17.94)	61 (20.26)
Rectum	45 (14.95)	45 (14.95)
Right hemicolon	26 (8.64)	17 (5.65)
Left hemicolon	9 (2.99)	6 (1.99)
Sigmoid colon	16 (5.31)	22 (7.31)

BMI: Body mass index; ASA: American Society of Anesthesiologists.

Primary endpoint

The incidence of SSI was significantly lower in the mirabilite group than in the control group (P = 0.042). There were 12 superficial and 3 deep SSIs in the mirabilite group, vs 22 superficial and 4 deep SSIs in the controls. Patients with superficial incisional SSI were successfully managed with wound care and drainage, while those with deep incisional SSI required additional antibiotic therapy alongside wound care and drainage. Additionally, the mirabilite group exhibited a significantly shorter time to first flatus compared to the control group [38 (18-75) hours vs 57 (17-90) hours, P < 0.001], indicating faster recovery of gastrointestinal function (Table 2).

Table 2 Comparison of perioperative indexes between the mirabilite and control groups, median (interquartile rage)/n (%)/mean ± SD.

Variable	Mirabilite group	Control group	P value
Surgical duration, min	161.0 (67-375)	165.0 (50-435)	0.694
Intraoperative blood loss, mL	100.0 (5-960)	100.0 (20-1000)	0.377
Incision length, cm	6.0 (4-12)	6.0 (4-10)	0.379
Time to first flatus, hours	38 (18-75)	57.0 (17-90)	< 0.001
Postoperative length of stay, days	8.5 (7-36)	9.0 (7-33)	0.028
Postoperative complication	7 (2.33)	12 (3.99)	0.335
Bowel obstruction	1	3
Anastomotic leakage	3	6
Pneumonia	3	3
SSI	15 (4.98)	26 (8.64)	0.042
Superficial SSI	12	22
Deep SSI	3	4
Organ/space SSI	0	0
Postoperative serum albumin level, g/L
Day 1	32.52 ± 3.88	32.12 ± 3.38	0.338
Day 4	34.77 ± 3.90	34.92 ± 3.99	0.741

SSI: Surgical site infection.

Secondary endpoint

The drainage volume in the mirabilite group was significantly lower than that in the control group (P < 0.01). Postoperative CRP levels were also lower in the mirabilite group (P = 0.038), and VAS pain scores were significantly lower than those in the control group (P = 0.027; Table 3). Postoperative hospital stay was significantly shorter in the mirabilite group [8.5 (7-36) days vs 9.0 (7-33) days, P = 0.028], as shown in Table 2. The shorter postoperative hospital stays in the mirabilite group, despite similar overall complication rates, likely results from the cumulative benefits observed: Reduced SSI minimized infectious management, accelerated gastrointestinal function facilitated earlier oral intake, and decreased pain and inflammation enhanced early mobilization. Together, these factors contributed to a more efficient recovery pathway and earlier discharge readiness. These findings suggest a promising trend that warrants further validation through large-scale, multicenter randomized controlled trials. There were no statistically significant group differences in albumin levels on postoperative days 1 and 4 (P = 0.338 and P = 0.741, respectively). Similarly, there were no significant differences in intraoperative blood loss [100.0 (5-960) mL vs 100.0 (20-1000) mL, P = 0.377] or incision length [6.0 (4-12) cm vs 6.0 (4-10) cm, P = 0.379; Table 2]. Aside from SSI, postoperative complications showed no significant differences between the two groups (P = 0.335), as detailed in Table 2. The mirabilite group had 7 cases of complications, including 1 of bowel obstruction, 3 of pneumonia, and 3 of anastomotic leakage, whereas the control group had 12 cases of complications, including 3 of bowel obstruction, 6 of anastomotic leakage, and 3 of pneumonia. Apart from three cases in the mirabilite group and six in the control group with anastomotic leakage requiring irrigation and drainage, all complications resolved with pharmacological treatment.

Table 3 Comparison of postoperative C-reactive protein, drainage, and Visual Analog Scale scores between the mirabilite and control groups, mean ± SD.

Variable	Mirabilite group	Control group	P value
C-reactive protein, mg/L			0.038
Day 1	43.58 ± 33.49	45.83 ± 37.90
Day 4	93.14 ± 53.51	101.92 ± 53.33
Day 7	47.35 ± 40.33	70.70 ± 50.68
VAS score			0.027
Day 1	1.71 ± 0.74	2.26 ± 0.72
Day 2	1.39 ± 0.61	2.09 ± 0.83
Day 3	1.18 ± 0.43	1.74 ± 0.76
Drainage, mL			< 0.01
Day 1	95.63 ± 5.92	98.71 ± 5.73
Day 2	66.63 ± 4.72	68.25 ± 4.84
Day 3	45.27 ± 4.87	47.58 ± 4.93
Day 4	27.97 ± 5.02	27.75 ± 7.70
Day 5	14.80 ± 4.17	15.76 ± 6.83
Day 6	8.67 ± 3.74	9.14 ± 3.64
Day 7	6.17 ± 2.92	5.63 ± 1.76

VAS: Visual analog scale.

DISCUSSION

External application of mirabilite is an effective treatment for surgical wound care, postoperative recovery, and anti-inflammatory therapy[16-18]. This study further confirmed that mirabilite effectively reduces the incidence of postoperative SSI and promotes gastrointestinal function recovery in gastrointestinal surgery patients. The experimental group had lower rates of SSI, shorter hospital stays, reduced drainage volume, lower CRP levels, and lower VAS scores compared to the control group, indicating that mirabilite can effectively prevent postoperative complications and accelerate recovery.

Our mirabilite group showed a significantly lower rate of SSI than the control group (P = 0.042), suggesting that mirabilite effectively reduces the risk of infection. SSIs are among the most common complications of gastrointestinal surgery, particularly due to exposure of the surgical site to the intestinal flora, which leads to a higher infection risk in gastrointestinal procedures[19]. Han et al[14] found that external application of mirabilite significantly reduced the incidence of SSI (P < 0.05) in patients after cesarean section, consistent with our results. Mirabilite promotes angiogenesis and tissue repair by enhancing the expression of vascular endothelial growth factor and extracellular regulated protein kinases, while reducing inflammatory responses[20].

Gastrointestinal function recovery is crucial for patient recovery after surgery. The time to first flatus was significantly earlier in our mirabilite group (P < 0.05), as was the hospital stay (8.5 days vs 9.0 days, P = 0.028). Topical mirabilite reduces postoperative abdominal edema through its osmotic properties, promoting the absorption of local inflammatory factors, improving intestinal circulation, and accelerating gastrointestinal function recovery[12]. Recovery of gastrointestinal function is influenced by a multifactorial process beyond the topical intervention studied here. Several well-established factors could act as potential confounders, including the type and duration of anesthesia, intraoperative and postoperative opioid use, surgical technique and trauma (e.g., open vs laparoscopic approach, extent of resection), operative time, intraoperative fluid management, and preoperative patient status (e.g., nutritional state, comorbidities like diabetes). In this study, we aimed to mitigate the influence of these confounders through a randomized design. As presented in Table 1, key baseline characteristics (e.g., age, BMI, comorbidity profiles) and major surgical parameters (e.g., operative time, blood loss, surgical approach distribution) were well-balanced between the mirabilite and control groups. Furthermore, all patients received standardized perioperative care protocols regarding anesthesia, analgesia, and fluid management. While this randomization and standardization strengthen the internal validity of our findings, we acknowledge that subtle variations in unmeasured or imperfectly controlled factors (e.g., individual variations in opioid sensitivity, minor differences in surgical technique among surgeons) could still exist and represent a potential source of residual confounding.

After stimulation with mirabilite, levels of substance P and neurokinin-1 receptor in rats decreased, reducing inflammation. Levels of vasoactive intestinal peptide and its receptors increased, which further improved intestinal and lung health through anti-inflammatory and immune-regulating effects[21]. Drainage volume is a critical indicator of postoperative recovery, as it reflects postoperative exudation, inflammation, and the presence of complications such as bleeding and anastomotic leakage[22]. In this study, the mirabilite group had a significantly lower drainage volume compared to the control group, with no significant group difference in albumin levels. This highlights the advantages of mirabilite. Postoperative inflammation is a key factor affecting wound healing and gastrointestinal function recovery[23]. The cooling sensation provided by mirabilite may enhance subjective comfort, contributing to a positive recovery experience. However, the observed significant improvements in objective parameters (reduced drainage volume, lower CRP levels, and earlier gastrointestinal recovery) strongly suggest a biological effect beyond placebo.

CRP is a significant biomarker for early detection of anastomotic leakage, providing valuable prognostic insight in postoperative management[24,25]. This study found that CRP levels were significantly lower in the mirabilite group compared to the control group (P < 0.05). Similar to previous research[26], mirabilite was shown to regulate local inflammatory factors such as IL-1, IL-6, and tumor necrosis factor-α, thereby reducing postoperative inflammation[17]. Postoperative pain is another important factor in patient recovery[27]. In this study, VAS pain scores on postoperative days 1-3 were significantly lower in the mirabilite group (P = 0.027), for the same reasons mentioned above.

The finding that topical mirabilite application effectively reduced SSI and enhanced gastrointestinal recovery may be attributed to its unique, multi-modal pharmacological mechanisms. Our choice of mirabilite over single-mechanism agents was specifically based on its potential to address the complex postoperative condition. The core challenges of postoperative recovery include controlling local inflammation, reducing tissue edema, and managing pain. The hypertonic property of mirabilite makes it an excellent physical dehydrating agent capable of actively absorbing exudate and promptly alleviating periwound swelling, thereby improving microcirculation[12,17]. Concurrently, growing evidence indicates that its active components possess bioactive anti-inflammatory properties, potentially optimizing the inflammatory process by modulating cytokine release. Additionally, the cooling and mild analgesic effect produced by its topical application directly improves patient comfort[12,14,16]. Thus, the action of mirabilite is not merely anti-inflammatory or osmotic but represents a synergy of “physical drainage”, “chemical anti-inflammation”, and “sensory analgesia”[11,16]. This explains its possible advantages in promoting overall recovery and provides mechanistic support for the plausibility of our results.

It is important to note the limitations of this study. First, this exploratory single-center, prospective randomized controlled trial, conducted in a Chinese population with a moderate sample size, may have limited generalizability, warranting future multicenter trials to further validate the findings. Second, the open-label design, necessitated by the nature of the intervention, may have introduced observer and measurement bias, particularly for subjective patient-reported outcomes like pain scores. However, objective measures (e.g., SSI incidence, laboratory values) were assessed by blinded personnel to mitigate this bias. Third, the follow-up was limited to 30 days postoperatively, focusing on early recovery. Long-term outcomes such as incisional hernia formation were not evaluated and merit investigation in future studies. Future studies should consider conducting double-blind, multicenter, large-sample clinical trials with extended follow-up periods to validate the long-term efficacy and safety of mirabilite application in a more diverse patient population.

CONCLUSION

External application of mirabilite is a safe and effective treatment that can reduce systemic (reflected by lower postoperative CRP levels) and local inflammation, alleviate clinical symptoms, accelerate recovery, and lower the rate of SSI in patients after gastrointestinal surgery. Mirabilite is affordable, easily accessible, and simple to use, making it suitable for widespread clinical application.