Daikenchuto accelerates the recovery from prolonged postoperative ileus after open abdominal surgery: a subgroup analysis of three randomized controlled trials

Toru Kono,Satoshi Morita,Shigetoyo Saji,Mitsuo Kusano,Masaki Kitajima,Mitsuo Shimada,Junichi Sakamoto,Yoshihiko Maehara,Takashi Kanematsu,Yasuto Sato,Keisuke Koeda,Hidetoshi Katsuno,Yuji Morine,Masaaki Nishi,Masahiko Watanabe,Koutarou Maeda,Kozo Yoshikawa,Hiroki Sokuoka

doi:10.1007/s00595-019-01787-9

Abstract

PurposeProlonged postoperative ileus (POI) is a common complication after open abdominal surgery (OAS). Daikenchuto (DKT), a traditional Japanese medicine that peripherally stimulates the neurogenic pathway, is used to treat prolonged POI in Japan. To analyze whether DKT accelerates the recovery from prolonged POI after OAS, we conducted a secondary analysis of three multicenter randomized controlled trials (RCTs).MethodsA secondary analysis of the three RCTs supported by the Japanese Foundation for Multidisciplinary Treatment of Cancer (project numbers 39-0902, 40-1001, 42-1002) assessing the effect of DKT on prolonged POI in patients who had undergone OAS for colon, liver, or gastric cancer was performed. The subgroup included 410 patients with no bowel movement (BM) before the first diet, a DKT group (n = 214), and a placebo group (n = 196). Patients received either 5 g DKT or a placebo orally, three times a day. The primary endpoint was defined as the time from the end of surgery to the first bowel movement (FBM). A sensitivity analysis was also performed on the age, body mass index and dosage as subgroup analyses.ResultsThe primary endpoint was significantly accelerated in the DKT group compared with the placebo group (p = 0.004; hazard ratio 1.337). The median time to the FBM was 113.8 h in the placebo group and 99.1 h in the DKT treatment group.ConclusionsThe subgroup analysis showed that DKT significantly accelerated the recovery from prolonged POI following OAS.Trial registration numberUMIN000026292.

Highlights

Postoperative ileus (POI), which is a routine and unavoidable consequence of major open abdominal surgery (OAS), is characterized by transient impairment of bowel motility [1,2,3]
In the non-main analysis group (n = 330), while no significant differences in background factors were found between the DKT and placebo groups, the dosages did differ between the groups (Table 1b)
Our study revealed that there was a statistically significant difference in the primary endpoint between the DKT and placebo groups in the main analysis cohort [stratified logrank test; p = 0.004; stratified hazard ratio (HR) 1.337; 95% confidence interval (CI) 1.096–1.631; Fig. 1]

Summary

Introduction

Postoperative ileus (POI), which is a routine and unavoidable consequence of major open abdominal surgery (OAS), is characterized by transient impairment of bowel motility [1,2,3]. Patients suffering from POI in the small and large intestines commonly recover 24–48 and 48–72 h after surgery, respectively [3, 4]. By contrast, prolonged POI, which continues postoperatively beyond day 4, is termed “pathologic POI” [1, 5]. Several mechanisms have been proposed to explain the pathogenesis of prolonged POI, especially that after OAS, including a disturbance of the neurogenic pathway [5, 6]. Several advances have been made in medical therapy to help reduce the incidence and severity of POI [5, 6], the number of people suffering with this condition remains high

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