The Addition of Transdermal Delivery of Neostigmine and Glycopyrrolate by Iontophoresis to Thrice Weekly Bowel Care in Persons with Spinal Cord Injury: A Pilot Study

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.

Keywords: difficulty with evacuation; glycopyrrolate; iontophoresis; neostigmine; neurogenic bowel; spinal cord injury.

Figure 1

Comparison of the time to bowel evacuation between the standard of bowel care or standard of bowel care plus neostigmine and glypyrrolate arms of the study. SOC = standard of care; NEO = neostigmine; GLY = glycopyrrolate. * p < 0.0001.

Figure 2

Representative qualitative measure of stool burden on abdominal radiograph after standard of care or standard of care plus neostigmine and glypyrrolate. Fecal burden: (a) marked stool throughout the colon, (b) moderate stool in the cecum; (c) moderate stool in the transverse and left colon, (d) moderate stool in the cecum. Loss of body weight after two weeks of standard of bowel care and the dual drug combination: (a,b), −4.4 kg; (c,d), −2.6 kg.

Figure 3

Findings of the ten question bowel survey after standard of care or standard of care plus neostigmine and glypyrrolate. Abscissa axis: A score of “1” represent fully satisfied or the best response; a score of “5” represents fully dissatisified or the worse response score. Ordinate axis labels: 1. Satisfaction with overall bowel management program during the past month; 2. Bowel control over the past month; Questions 3 to 7, 9, and 10 are asked during the past 7 days: 3. Bowel control over; 4. Use of enemas for bowel control; 5. Use of laxatives; 6. Digital stimulation; 7. Number of bowel movements (1: 7 times or more, 2: 5–6 times, 3: 3–4 times, 4: 1–2 times, 5: none); 8. Average time spent to have a bowel evacuation per bowel care session; 9. Total time in the past week; and 10. Discomfort rating. SOC = standard of care; SOC and NEO + GLY = standard of care plus neostigmine and glycopyrrolate.

Figure 4

Findings of the Treatment Satisfaction Survey after Standard of Care or after Standard of Care plus Neostigmine and Glypyrrolate. The treatment satisfaction questionnaire for medications [10] was adapted by having all questions scored on a 7-point scale, except question 4 which had a dichotomous answer Abscissa: (−3) Extremely dissatisfied, (−2) Dissatisfied, (−1) Mildly dissatisfied, (0) Ambivalent, (1) Mildly Satisfied, (2) Satisfied, (3) Extremely Satisfied. Ordinate Axis: 1. Ability of medication to treat DWE; 2. Ability of medication to relieve symptoms; 3. Delay in its effect; 4. Side-effects of SOC and NEO + GLY, 5 subjects answered “yes”, 1 subjects answered “no”; 5. How bothersome are the side-effects? 6. Side-effects and physical function and health; 7. Side-effects and mental function and health; 8. Side-effects affecting satisfaction with the medication; 9. Difficulty in use; 10. Difficulty in planning; 11. Convenience in following instructions; 12. General satisfaction with the medication; 13. How certain are you that the good things about your medication outweigh the bad things? 14. Taking all things into account, how satisfied or dissatisfied are you with this medication? SOC = standard of care; SOC and NEO + GLY = standard of care plus neostigmine and glycopyrrolate.