Bowel Management Table 13: Treatment Studies Using Pharmacology for Neurogenic Bowel after SCI

Author Year; Country

Score

Research Design

Total Sample Size

Methods

Outcome

Rosman et al. 2008;

USA

PEDro = 8

Crossover RCT

N = 7

Population: 7 SCI subjects with defecatory problems (mean (SD) age: 46.9 (3.4) yrs, range 30 – 56 yrs); 4 cervical, 3 thoracic.

Treatment:injections of neostigmine (2 mg) and glycopyrrolate (0.4 mg) for 1 week, wash-out period for 1 week, and placebo for 1 week, in random order

Outcome Measures:Total bowel evacuation time; time to first flatus; time to beginning of stool flow; time to end of stool flow.

  1. Compared with placebo, neostigmine/glycopyrrolate significantly reduced the total bowel evacuation time (mean (SD)) from 98.1 (7.2) min to 74.8 (5.8) min
  2. Neostigmine/glycopyrrolate significantly reduced the mean (SD) time to first flatus from 56.9 (5.4) min to 21.8 (4.5) min
  3. Neostigmine/glycopyrrolate significantly reduced the mean (SD) time to beginning of stool flow from 69.8 (2.8) to 42.3 (6.4) min, and time to end of stool flow from 80.3 (4.0) to 53.3 (8.3) min.

Krogh et al. 2002;

Denmark

PEDro = 7

Double blind RCT

N=22

Population: mean (SD) age: 34.7 (2.5) yrs (placebo), 36.5 (3.9) yrs (1mg group), 44.3 (3.1) yrs (2mg group). No information on level of injury was reported.

Treatment: Subjects randomized with double blind design to treatment with prucalopride 1mg or placebo, taken once daily for 4 wks. A 2nd group of subjects was randomized to prucalopride 2mg or placebo for 4wks

Outcome measures: constipation; urinary habit; constipation severity and symptoms; colonic transit times

  1. Compared with baseline, constipation severity decreased with prucalopride. The VAS score for treatment efficacy showed a clear dose response (medians 4, 52, and 73 for placebo, 1 and 2 mg, respectively).
  2. Self-report diary showed an improvement in average weekly frequency of all bowel movements over 4 wks within the 2 mg group (median 0.6).
  3. 3 subjects (2 mg group) reported moderate/severe abdominal pain and 2 discontinued treatment. Adverse events (AEs) were reported by 6/7 in the placebo group, and by 7/8 and 6/8 in the 1 and 2mg groups. The most common AEs were gastrointestinal (flatulence, abdominal pain and diarrhea).

Korsten et al. 2005;

USA

PEDro = 6

RCT

N=13

 

Population: Level of injury: C4-T12 (5  tetraplegics, 8 paraplegics; 12/13 motor complete, 5/13 sensory incomplete); Age: mean (range) 46 (25-69)yrs; Duration of injury: mean (range) 14 (1-31)yrs

Treatment: On different days, subjects received, in a randomized, double-blinded design, one of three intravenous infusions (normal saline, 2 mg neostigmine, or 2 mg neostigmine and 0.4 mg glycopyrrolate)

Outcome Measures: time to bowel evacuation using barium paste

  1. Neostigmine and the combination of neostigmine and glycopyrrolate both caused a similar expulsion of the stool, which was greater than with normal saline (median score 3 vs. 4 vs. 0, respectively)
  2. Mean time to expulsion was 11.5 min (range 5-20 min) after neostigmine and 13.5 min (range 4-23 min) after the combination.
  3. There was no correlation between the level of SCI and likelihood of bowel evacuation with any of the infusions.

Cardenas et al. 2007;

USA

PEDro = 6

RCT

N=91

Population: 91 subjects with motor-incomplete SCI randomized to three groups:

(I) Fampridine, sustained release, 25 mg bid: Level of injury: 23 cervical, 7 thoracic; AIS grade: 14 C, 16 D; 22M:8F; Age: mean (range) 44 (23-66)yrs; Duration of injury: mean (range) 8.3 (1-30)yrs

(II) 40 mg bid: Level of injury: 24 cervical, 6 thoracic; AIS grade: 12 C, 18 D 26M:,4F; Age: mean (range) 42 (21-67)yrs; Duration of injury: 10.8 years, range 1-35;

(III) Placebo: Level of injury: 26 cervical, 5 thoracic; AIS grade: 18 C, 13 D; 24M:7F; Age: mean (range) 38 (19-61)yrs; Duration of injury: mean (range) 8.3 (1-37)yrs

Treatment: Drug treatment (Fampridine orally 25mg bid or 40mg bid) or placebo for 8 weeks

Outcome Measures: Number of days with bowel movement, Subject Global Impression (SGI), Ashworth

  1. A significantly larger number of subjects in the 25 mg bid (6/30 subjects) and 40 mg bid (7/30 subjects) groups had an increase in the number of days with bowel movements compared to subjects in the placebo group. Number of days increase not reported.
  2. In total 78% of subjects completed the study. More (13/30) discontinued from Group II than Group I (4/30) and Group III (3/31). The most frequent AEs were hypertonia, generalized spasm, insomnia, dizziness, asthenia, pain, constipation, and headache. One subject in Group II suffered a seizure.
  3. SGI changed significantly in favor of Group I (mean=4.5). Group II had a mean of 3.6 and Group III had a mean of 3.9.
  4. Subgroup analysis of subjects with baseline Ashworth scores >1 showed significant improvement in spasticity in Group I versus Group III (Ashworth mean score: Group I= 1.0; Group 2= 1.1; Group III= 1.2).

Segal et al. 1987;

USA

Prospective Controlled Trial

N=28

Population: 11 subjects with tetraplegia, 9 subjects with paraplegia (all complete SCI), 8 able-bodied controls; Age range: 20-55yrs

Treatment: subjects ingested a liquid meal, then within 2 weeks, ingested 2nd liquid meal while metoclopramide (10mg) was administered intravenously; gastric emptying (GE) was evaluated after each liquid meal

Outcome Measures: half time of gastric emptying, gastric emptying patterns in the early and later phases

  1. The mean GE half time for a liquid meal decreased in the subjects with tetraplegia from 104.8 min to 18.8 min after treatment with metoclopramide.
  2. The pretreatment mean GE of 111.5 min decreased to 29.1 min among the subjects with paraplegia.
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