Other treatments
Another way to improve the postoperative period and reduce transit recovery time is to optimise analgesia and, more importantly, to obtain analgesia by reducing the administration of opiates. Lidocaine has been studied to this end (Foo et al., 2021). Lidocaine is a local amino-amide anaesthetic. Intravenously, lidocaine is 60-80% protein-bound, mostly to a 1-acidic glycoprotein. Lidocaine crosses the blood-brain barrier by passive diffusion across membranes (Hermanns et al., 2019). The main mechanism of action of lidocaine as a local anaesthetic is blockade of voltage-gated sodium channels, resulting in reversible blockade of the propagation of action potentials (Cardoso and Lewis, 2018). Lidocaine acts on neuroinflammatory phenomena by controlling pain signals (Hermanns et al., 2019). It acts directly by blocking inhibitory sympathetic afferent and efferent pathways and prevertebral reflex arcs involved in the neurogenic phase of ileus (Hollmann and Durieux, 2000). In addition, in-vitro and animal model studies have shown that the administration of lidocaine reduces the production of pro-inflammatory cytokines such as TNFα IL-1β and IL6 (Wang et al., 2018). Numerous controlled trials have demonstrated a clinical benefit of intravenous lidocaine administration and these results have been confirmed by several meta-analyses (Sun et al., 2012). Thoracic epidural analgesia (TAE) is another interesting strategy for postoperative pain control. A controlled clinical trial compared a group of patients treated with intravenous lidocaine (n=16) to a group of patients with TAE (n=26) and found no difference in time to transit and food intake (Swenson et al., 2010). The efficacy of analgesics, therapeutics and strategies highlights the critical role of pain control in POI, and the relationship between the enteric nervous system and inflammation.
Daikenchuto (DKT) is a traditional Japanese preparation comprising three different herbs (dried ginger, ginseng and zanthox-ylum fruit) known for their effects on intestinal motility (Kubota et al., 2019). Animal model studies have shown a beneficial effect on POI via an anti-inflammatory effect by acting on nicotinic acetylcholine receptors. A recent meta-analysis comprising six controlled trials and one cohort study from Japan, included 1134 patients overall (588 DKT-treated patients). Three studies included colorectal cancer patients, two studies focused on gastric cancer patients and two on pancreatic resection cohorts. The analysis found a significant reduction in the rate of postoperative ileus in the DKT group (RR= 0.58, p=0.04, I2=48%)(Ishizuka et al., 2017). A 16-centre Phase 2 study in the US involving 69 patients with enrolment completed in June 2020 is currently underway to evaluate DKT (NCT02232893). Endo et al. recently identified Zingiberis Siccatum Rhizoma, a component of DKT, as an activator of the 7AChR alpha receptor via activation of transient receptor potential ankyrin 1(TRPA1 channels on enterochromaffin cells, resulting in stimulation of 5-HT4 receptors in the enteric nervous system(Endo et al., 2017).