ABSTRACT
Persons with spinal cord injury (SCI) have neurogenic bowel disorders characterized by difficulty with evacuation (DWE), fecal incontinence, and discoordination of defecation. Six medically stable in-patients with SCI with a mean age of 57 ± 10 years (range: 39-66 years) and time since injury of 18 ± 17 years (range: 3-47 years) were investigated. Standard of care (SOC) for bowel care was followed by two weeks of SOC plus neostigmine (0.07 mg/kg) and glycopyrrolate (0.014 mg/kg) administered transcutaneously by iontophoresis thrice weekly for two weeks while patients continued to receive SOC. The primary endpoint was time to bowel evacuation. Body weights and abdominal radiographs were obtained. Ten questions related to bowel function and the Treatment Satisfaction Questionnaire for Medication were acquired after each arm. Bowel evacuation time decreased after the dual drug intervention arm (106.9 ± 68.4 vs. 40.8 ± 19.6 min; p < 0.0001). Body weight decreased (2.78 ± 0.98 kg; p < 0.0001), a finding confirmed on abdominal radiograph. Both questionnaires demonstrated improvement after the dual drug intervention arm. No major adverse events occurred. The addition of neostigmine and glycopyrrolate by transcutaneous administration to SOC for bowel care in persons with SCI and DWE resulted in the safe, effective, and predictable bowel evacuation with subjective improvement in bowel care.
ABSTRACT
STUDY DESIGN: Phase I Clinical Trial. OBJECTIVES: In this proof-of-principle study, the effectiveness and safety of transdermal administration of neostigmine/glycopyrrolate to elicit a bowel movement was compared to intravenous administration in patients with spinal cord injury. SETTING: James J. Peters Veterans Affairs Medical Center (Bronx, NY). METHODS: Individuals were screened for responsiveness (Physical Response) to intravenous neostigmine (0.03 mg/kg)/glycopyrrolate (0.006 mg/kg). Intravenous neostigmine/glycopyrrolate responders (Therapeutic Response) were administered low-dose transdermal neostigmine/glycopyrrolate [(0.05 mg/kg)/(0.01 mg/kg)] by iontophoresis. Non-responders to low-dose transdermal neostigmine/glycopyrrolate were administered high-dose transdermal neostigmine/glycopyrrolate [(0.07 mg/kg)/(0.014 mg/kg)] by iontophoresis. Bowel movement, bowel evacuation time, and cholinergic side effects were recorded. Visits were separated by 2 to 14 days. RESULTS: Eighteen of 25 individuals (72.0%) had a bowel movement (20 ± 22 min) after intravenous neostigmine/glycopyrrolate. Of these 18 individuals, 5 individuals experienced a bowel movement with low-dose transdermal neostigmine/glycopyrrolate. Another five individuals had a bowel movement after high-dose transdermal neostigmine/glycopyrrolate administration. Fewer side effects were observed in individuals who received neostigmine/glycopyrrolate transdermally compared to those who were administered intravenous neostigmine/glycopyrrolate. CONCLUSIONS: Transdermal administration of neostigmine/glycopyrrolate by iontophoresis appears to be a practical, safe, and effective approach to induce bowel evacuation in individuals with spinal cord injury.
