Original Contribution | Published:

Functional GI Disorders

Infusion of Neostigmine–Glycopyrrolate for Bowel Evacuation in Persons with Spinal Cord Injury

The American Journal of Gastroenterology volume 100, pages 15601565 (2005) | Download Citation

Material in this paper was presented, in part, at the meeting of the American Gastroenterological Association held during May 2003 in Orlando, FL and published in abstract form in Gastroenterology 2003; 124(Suppl 1):A-115.

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Abstract

Defecatory complications are common after spinal cord injury (SCI) and have been attributed, in part, to an imbalance of the autonomic nervous system between parasympathetic and sympathetic effects on the colon. Because parasympathetic (i.e., cholinergic) input to the bowel may be downregulated after SCI, it was hypothesized that neostigmine, a medication that increases cholinergic tone by blocking the metabolism of acetylcholine, might promote bowel evacuation in these persons. Since neostigmine is known to cause bradycardia and bronchoconstriction, we also assessed whether these side-effects could be prevented by coadministration of neostigmine with glycopyrrolate, an anticholinergic agent that has limited activity on the muscarinic receptors of the colon. The hypothesis was tested in 13 persons with SCI in whom videofluoroscopy was carried out after instillation of a barium oatmeal paste into the rectum and descending colon. On separate days, subjects received, in a randomized, blinded design, one of three intravenous infusates (normal saline, 2 mg neostigmine, or 2 mg neostigmine + 0.4 mg glycopyrrolate). The effect of these infusates on bowel evacuation of the barium paste, heart rate, and airway resistance was determined. Both neostigmine and neostigmine + glycopyrrolate resulted in prompt bowel evacuation. The nadir heart rate was lower after neostigmine alone than with the combination. Neostigmine administration increased both total and central airway resistance, an effect that was not observed with the coadministration of glycopyrrolate. Other side-effects of neostigmine and the combination of drugs included muscle fasciculations and dry mouth, both of which were mild and short-lived. Abdominal cramping was noted in subjects with spinal cord lesions below thoracic level 10. These results indicated that neostigmine/glycopyrrolate administration is safe and well tolerated in persons with chronic SCI.

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References

  1. 1.

    , , , et al. Delayed colonic transit in spinal cord-injured patients measured by indium-111 Amberlite scintigraphy. Am J Gastroenterol 1995;90: 1295–1300.

  2. 2.

    , , , et al. Colostomy as treatment for complications of spinal cord injury. Arch Phys Med Rehabil 1990;71: 514–518.

  3. 3.

    , , . Gastrointestinal and segmental colonic transit times in patients with acute and chronic spinal cord lesions. Spinal Cord 2000;38: 615–621.

  4. 4.

    , . Bowel dysfunction in spinal-cord-injury patients. Lancet 1996;347: 1651–1653.

  5. 5.

    , , . Neurogenic bowel dysfunction after spinal cord injury: Clinical evaluation and rehabilitative management. Arch Phys Med Rehabil 1997;78: S86–S102.

  6. 6.

    , , . Pattern of change of bronchomotor tone following reversal of neuromuscular blockade. Br J Anaesth 1983;55: 955–959.

  7. 7.

    . Clinical application of forced oscillation. Pulm Pharmacol Ther 2001;14: 341–350.

  8. 8.

    , , . Gastrointestinal complications of spinal cord injury. Spine 1981;6: 538–544.

  9. 9.

    , , , et al. Chronic gastrointestinal problems in spinal cord injury patients: A prospective analysis. Am J Gastroenterol 1990;85: 1114–1119.

  10. 10.

    , , , et al. Large-bowel transit in paraplegic patients. Dis Colon Rectum 1987;30: 924–928.

  11. 11.

    , , , et al. The effect of cisapride on segmental colonic transit time in patients with spinal cord injury. Am J Gastroenterol 1995;90: 285–289.

  12. 12.

    , . Colonic motility and tone after spinal cord and cauda equina injury. Am J Gastroenterol 1997;92: 891–894.

  13. 13.

    , , , et al. The effect of provocative maneuvers on heart rate variability in subjects with quadriplegia. Am J Physiol 1995;268: H2239–H2245.

  14. 14.

    , , , et al. Sympathovagal balance of autonomic control of the heart in subjects with spinal cord injury. Am J Physiol 1997;272: H835–H842.

  15. 15.

    , , , et al. Cholinergic stimulation enhances colonic motor activity, transit, and sensation in humans. Am J Physiol Gastrointest Liver Physiol 2001;281: G1228–G1237.

  16. 16.

    . Muscarinic receptor subtypes: Physiology and clinical implications. N Engl J Med 1989;321: 1022–1028.

  17. 17.

    , , , et al. Ogilvie's Syndrome: A new approach to an old problem. Dis Colon Rectum 1995;38: 424–427.

  18. 18.

    , , . Neostigmine for the treatment of acute colonic pseudo-obstruction. N Engl J Med 1999;341: 137–141.

  19. 19.

    . Prevention of neostigmine-induced colonic activity: A comparison of atropine and glycopyrronium. Anaesthesia 1984;39: 1083–1085.

  20. 20.

    , , , et al. Effects of neostigmine and atropine on motor activity of ileum, colon, and rectum of anaesthetized subjects. BMJ 1970;1: 793–794.

  21. 21.

    , , . Letter to the editor. N Engl J Med 1999;341: 1622.

  22. 22.

    , , , et al. Airway hyperreactivity in subjects with tetraplegia is associated with reduced baseline airway caliber. Chest 2000;118: 1397–1404.

  23. 23.

    , , , et al. Airway hyperresponsiveness to methacholine in subjects with spinal cord injury. Chest 1996;110: 911–915.

  24. 24.

    , , , et al. Bronchial hyperresponsiveness after cervical spinal cord injury. Chest 1994;105: 1073–1076.

  25. 25.

    , , , et al. Bronchodilatory effects of ipratropium bromide in patients with tetraplegia. Paraplegia 1995;33: 274–277.

  26. 26.

    , . Prostigmin assessment test of fertility in spinal man. Paraplegia 1971;1: 39–50.

  27. 27.

    , , , et al. Treatment of anejaculation in the total paraplegic by subcutaneous injection of physostigmine. Paraplegia 1983;21: 30–36.

  28. 28.

    , , , et al. Neostigmine/glycopyrrolate accelerates bowel evacuation in patients with spinal cord injury and defecatory disorders. Gastroenterology 2005;128: in press.

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Acknowledgements

This work was supported by the Department of Veterans Affairs (VA) Rehabilitation Research and Development Center for Excellence on the Medical Consequences of SCI. We also wish to thank Reagan Mendoza, M.D., Robert Paulino, M.D., Grace Lirio, M.D., Roberta Modeste-Duncan, B.S., and Catherine Harris, H.T. for their expert technical and administrative assistance.

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Affiliations

  1. VA Medical Center, Bronx, New York; and Mount Sinai School of Medicine, New York, New York

    • Mark A Korsten
    • , Alan S Rosman
    • , Anthony Ng
    • , Erdal Cavusoglu
    • , Ann M Spungen
    • , Miroslav Radulovic
    • , Jill Wecht
    •  & William A Bauman

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Correspondence to Mark A Korsten.

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https://doi.org/10.1111/j.1572-0241.2005.41587.x

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