Prokinetic Agents

Chronic constipation is a common problem after SCI, with a prevalence of up to 80% of affected individuals (Krogh et al. 2002).

Five studies exploring the use of cisapride for neurogenic bowel management have been removed from this review as the drug is no longer available.

Discussion

Prokinetic agents are presumed to promote transit through the GI tract, thereby decreasing the length of time needed for stool to pass through the intestines and increasing the amount of stool available for evacuation. Since constipation in patients with both acute and chronic SCI is considered primarily a consequence of prolonged colonic transit time, stimulating intestinal motility would appear to be a reasonable therapeutic approach.

There is little evidence on the use of metoclopramide and neostigmine in routine bowel management. Segal et al. (1987) investigated the use of metoclopramide (a potent dopamine receptor antagonist with prokinetic properties) for enhancing gastric emptying in individuals with SCI. They found that impaired gastric emptying in patients with SCI can be significantly improved using metoclopramide. Korsten et al. (2005) found that neostigmine (a reversible cholinesterase inhibitor), or the combination of neostigmine and glycopyrrolate administered intravenously, improved stool expulsion compared to placebo. Rosman et al. (2008) reported similar findings for this combination over placebo, in which they reported significantly reduced total bowel evacuation time (p<0.05), mean time to first flatus (p=0.001), mean time to beginning of stool flow (p=0.01), and mean time to end of stool flow (p<0.05). Additionally, administration of this combination by transdermal iontophoresis has been examined in comparison to intravenous methods (Korsten et al. 2018; Bauman et al. 2021). Bauman et al. (2021) found a reduction in bowel evacuation time after transdermal iontophoresis when investigating this treatment in standard of care, indicating that both administration methods may be effective and safe for people with SCI.

Improvement in constipation and increased frequency of bowel movement were also seen with the use of prucalopride – a novel, highly selective serotonin receptor agonist with enterokinetic properties that facilitates cholinergic and excitatory non-adrenergic, non-cholinergic neurotransmission (Krogh et al. 2002; N=22).

Conclusion

Prucalopride:

There is level 1b evidence (from one RCT; Krogh et al. 2002) that prucalopride increases stool frequency, improves stool consistency, and decreases gastrointestinal GI transit time; higher doses (2mg/day) were associated with moderate/severe abdominal pain.

Metoclopramide:

There is level 2 evidence (from one prospective controlled trial; Segal et al. 1987) that intravenous administration of metoclopramide decreases time of gastric emptying.

Neostigmine:

There is level 1b evidence (from one RCT; (Korsten et al. 2005) that neostigmine, administered with or without glycopyrrolate, leads to a greater expulsion of stool.

There is level 1 (Rosman et al. 2008) that neostigmine with glycopyrrolate decreases total bowel evacuation times and improves bowel evacuation.

There is level 2 evidence (Korsten et al. 2018) that transdermal administration of neostigmine/glycopyrrolate with iontophoresis can effectively and safely stimulate bowel movement in people with SCI and may have fewer side effects in comparison to intravenous administration.

There is level 4 evidence (Bauman et al. 2021) that using neostigmine/glycopyrrolate in bowel care regimens is a safe and effective way to reduce the time to bowel evacuation.