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).