Efficacy and Safety of Subcutaneous Neostigmine for Ileus,Acute Colonic Pseudo-obstruction,or Refractory Constipation

Background: Neostigmine is traditionally administered intravenously for treatment of acute colonic pseudo-obstruction (ACPO), though use is associated with administration constraints and adverse effects. Objective: To evaluate whether an alternative route of administration for neostigmine via subcutaneous (SQ) delivery is safe and effective in a broad cohort of medical and surgical patients. Methods: This multicenter, retrospective observational study included adult patients administered SQ neostigmine for ileus, ACPO, or refractory constipation. Efficacy indicators were time to first bowel movement (BM) following initiation of the medication, total SQ neostigmine dose administered to produce a BM, and administration of a rescue intervention to produce a BM. Safety events evaluated were cardiac arrest, bradycardia, bronchospasm requiring intervention, nausea requiring intervention, or severe salivation, lacrimation, or diarrhea. Results: A total of 182 patients were eligible for inclusion. The most commonly utilized dosing strategy of neostigmine was 0.25 mg SQ 4 times daily. The median time to first BM following initiation of SQ neostigmine was 29.19 hours (interquartile range = 12.18-56.84) with a median dose administered before first BM of 1.25 mg. Three patients (1.65%) experienced an adverse drug event leading to drug discontinuation, with 2 developing bradycardia that resolved with drug discontinuation alone. Conclusions: SQ neostigmine may be reasonable for management of ileus, ACPO, or refractory constipation, though use should be avoided in patients with new-onset heart block, a history of second-degree heart block, or following bowel resection with primary anastomosis. Despite the low incidence of adverse drug events observed, monitoring for bradycardia with telemetry may be considered.