Editorial Type:
Digestive System – Nutrition

A randomized crossover study of compounded liquid sildenafil for treatment of generalized megaesophagus in dogs

Susan O. Mehain Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA

Search for other papers by Susan O. Mehain in
Current site
Google Scholar
PubMed Close
 DVM, MS
,
Jillian M. Haines Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA

Search for other papers by Jillian M. Haines in
Current site
Google Scholar
PubMed Close
 DVM, MS
, and
Sarah C. Guess Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA

Search for other papers by Sarah C. Guess in
Current site
Google Scholar
PubMed Close
 DVM, MS
DOI:
https://doi.org/10.2460/ajvr.21.02.0030
Volume/Issue:
Volume 83: Issue 4
Online Publication Date:
21 Jan 2022
Restricted access
Sign In Reprints and Permissions Purchase Article

Abstract

OBJECTIVE

To determine whether delivery of compounded liquid sildenafil directly to the stomach of dogs with megaesophagus (ME) would affect esophageal clearance, regurgitation frequency, body weight, or quality of life.

ANIMALS

10 client-owned otherwise healthy dogs with stable ME.

PROCEDURES

A randomized crossover study was performed. Dogs received either sildenafil (1 mg/kg, PO, q 12 h) or a placebo for 14 days, followed by a 7-day washout period, then the opposite treatment for 14 days. Esophageal clearance time was assessed by means of videofluoroscopy prior to treatment and on day 1 of each treatment period. Owners maintained logs of regurgitation episodes and quality of life.

RESULTS

Compounded liquid sildenafil moved into the stomach during 21 of 30 (70%) videofluoroscopy sessions. Sildenafil resulted in a significant reduction in the number of regurgitation episodes (median, 3.5 episodes/wk; range, 0 to 14.5 episodes/wk), compared with baseline (median, 6.5 episodes/wk; range, 1.5 to 19.5 episodes/wk) and the placebo (median, 4 episodes/wk; range, 0 to 28 episodes/wk), and a significant increase in body weight (median, 22.05 kg; range, 6 to 26.3 kg), compared with baseline (median, 21.55 kg; range, 5.1 to 26.2 kg) and the placebo (median, 22.9 kg; range, 5.8 to 25.9 kg). There were no differences in esophageal clearance times or quality-of life-scores between sildenafil and placebo.

CLINICAL RELEVANCE

Although significant differences with placebo administration were identified, clinically relevant improvements were not seen with the use of compounded liquid sildenafil in dogs with ME.

Abstract

OBJECTIVE

To determine whether delivery of compounded liquid sildenafil directly to the stomach of dogs with megaesophagus (ME) would affect esophageal clearance, regurgitation frequency, body weight, or quality of life.

ANIMALS

10 client-owned otherwise healthy dogs with stable ME.

PROCEDURES

A randomized crossover study was performed. Dogs received either sildenafil (1 mg/kg, PO, q 12 h) or a placebo for 14 days, followed by a 7-day washout period, then the opposite treatment for 14 days. Esophageal clearance time was assessed by means of videofluoroscopy prior to treatment and on day 1 of each treatment period. Owners maintained logs of regurgitation episodes and quality of life.

RESULTS

Compounded liquid sildenafil moved into the stomach during 21 of 30 (70%) videofluoroscopy sessions. Sildenafil resulted in a significant reduction in the number of regurgitation episodes (median, 3.5 episodes/wk; range, 0 to 14.5 episodes/wk), compared with baseline (median, 6.5 episodes/wk; range, 1.5 to 19.5 episodes/wk) and the placebo (median, 4 episodes/wk; range, 0 to 28 episodes/wk), and a significant increase in body weight (median, 22.05 kg; range, 6 to 26.3 kg), compared with baseline (median, 21.55 kg; range, 5.1 to 26.2 kg) and the placebo (median, 22.9 kg; range, 5.8 to 25.9 kg). There were no differences in esophageal clearance times or quality-of life-scores between sildenafil and placebo.

CLINICAL RELEVANCE

Although significant differences with placebo administration were identified, clinically relevant improvements were not seen with the use of compounded liquid sildenafil in dogs with ME.

Supplementary Materials

    • Supplementary Appendix S1 (PDF 682 KB)
    • Supplementary Appendix S2 (PDF 20 KB)

Contributor Notes

Corresponding author: Dr. Haines (jmhaines@wsu.edu)
Cover American Journal of Veterinary Research
American Journal of Veterinary Research
Publication Date:
01 Apr 2022
  • 1.

    Marks S. Diseases of the pharynx and esophagus. In: Ettinger S, Feldman E, Côté E, eds. Textbook of Veterinary Internal Medicine. 8th ed. Elsevier; 2017:1476–1490.

    • Search Google Scholar
    • Export Citation
  • 2.

    Harvey CE, O’Brien JA, Durie VR, Miller DJ, Veenema R. Megaesophagus in the dog: a clinical survey of 79 cases. J Am Vet Med Assoc. 1974;165(5):443–446.

    • Search Google Scholar
    • Export Citation
  • 3.

    Washabau RJ. Gastrointestinal motility disorders and gastrointestinal prokinetic therapy. Vet Clin North Am Small Anim Pract. 2003;33(5):1007–1028. doi:10.1016/S0195-5616(03)00076-7

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Boudrieau R, Rogers W. Megaesophagus in the dog: a review of 50 cases. J Am Anim Hosp Assoc. 1985;21(1):33–40.

  • 5.

    Glidewell H. Clinical signs of idiopathic megaesophagus in Great Dane puppies. Vet Med Small Anim Clin. 1983;78:37–45.

  • 6.

    Guilford W, Strombeck D. Diseases of swallowing. In: Guilford WG, Center SA, Strombeck DR, Williams DA, Meyer DJ, eds. Strombeck’s Small Animal Gastroenterology. 3rd ed. WB Saunders Co; 1996:211–238.

    • Search Google Scholar
    • Export Citation
  • 7.

    McBrearty AR, Ramsey IK, Courcier EA, Mellor DJ, Bell R. Clinical factors associated with death before discharge and overall survival time in dogs with generalized megaesophagus. J Am Vet Med Assoc. 2011;238(12):1622–1628. doi:10.2460/javma.238.12.1622

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Simpson J. Management of megaoesophagus in the dog. In Pract. 1994;16(1):14–16. doi:10.1136/inpract.16.1.14

  • 9.

    Patel DA, Kim HP, Zifodya JS, Vaezi MF. Idiopathic (primary) achalasia: a review. Orphanet J Rare Dis. 2015;10:89. doi:10.1186/s13023-015-0302-1

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Bortolotti M, Mari C, Lopilato C, Porrazzo G, Miglioli M. Effects of sildenafil on esophageal motility of patients with idiopathic achalasia. Gastroenterology. 2000;118(2):253–257. doi:10.1016/S0016-5085(00)70206-X

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Bortolotti M, Mari C, Giovannini M, Pinna S, Miglioli M. Effects of sildenafil on esophageal motility of normal subjects. Dig Dis Sci. 2001;46(11):2301–2306. doi:10.1023/A:1012383424783

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Bortolotti M, Pandolfo N, Giovannini M, Mari M, Miglioli M. Effect of sildenafil on hypertensive lower oesophageal sphincter. Eur J Clin Invest. 2002;32(9):682–685. doi:10.1046/j.1365-2362.2002.01059.x

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Eherer AJ, Schwetz I, Hammer HF, et al. Effect of sildenafil on oesophageal motor function in healthy subjects and patients with oesophageal motor disorders. Gut. 2002;50(6):758–764. doi:10.1136/gut.50.6.758

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Moreland RB, Goldstein I, Traish A. Sildenafil, a novel inhibitor of phosphodiesterase type 5 in human corpus cavernosum muscle cells. Life Sci. 1998;62(20):309–318. doi:10.1016/S0024-3205(98)00158-1

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Rhee PL, Hyun JG, Lee JH, et al. The effect of sildenafil on lower esophageal sphincter and body motility in normal male adults. Am J Gastroenterol. 2001;96(12):3251–3257. doi:10.1016/S0002-9270(01)03884-9

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Zhang X, Tack J, Janssens J, Sifrim DA. Effect of sildenafil, a phosphodiesterase-5 inhibitor, of oesophageal peristalsis and lower oesophageal sphincter function in cats. Neurogastroenterol Motil. 2001;13(4):325–331. doi:10.1046/j.1365-2982.2001.00271.x

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Quintavalla F, Menozzi A, Pozzoli C, et al. Sildenafil improves clinical signs and radiographic features in dogs with congenital idiopathic megaesophagus: a randomized controlled trial. Vet Rec. 2017;180(16):404. doi:10.1136/vr.103832

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Harris RA, Grobman ME, Allen MJ, et al. Standardization of a videofluoroscopic swallow study protocol to investigate dysphagia in dogs. J Vet Intern Med. 2017;31(2):383–393. doi:10.1111/jvim.14676

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Walker DK. Pharmacokinetics and metabolism of sildenafil in mouse, rat, rabbit, dog and man. Xenobiotica. 1999;29(3):297–310. doi:10.1080/004982599238687

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Haines JM, Khoo A, Brinkman E, Thomason JM, Mackin AJ. Technique for evaluation of gravity-assisted esophageal transit characteristics in dogs with megaesophagus. J Am Anim Hosp Assoc. 2019;55(4):167–177. doi:10.5326/JAAHA-MS-6711

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Akabane R, Sato T, Sakatani A, Miyagawa Y, Tazaki H, Takemura N. Pharmacokinetics of single-dose sildenafil administered orally in clinically healthy dogs: effect of feeding and dose proportionality. J Vet Pharmacol Ther. 2018;41(3):457–462. doi:10.1111/jvp.12487

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Eardley I, Ellis P, Boolell M, Wulff M. Onset and duration of action of sildenafil for the treatment of erectile dysfunction. Br J Clin Pharmacol. 2002;53(suppl 1):61S–65S. doi:10.1046/j.0306-5251.2001.00034.x

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Nichols DJ, Muirhead GJ, Harness JA. Pharmacokinetics of sildenafil citrate after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality. Br J Clin Pharmacol. 2002;53(suppl 1):5S–12S. doi:10.1046/j.0306-5251.2001.00027.x

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Brown AJ, Davison E, Sleeper MM. Clinical efficacy of sildenafil in treatment of pulmonary arterial hypertension in dogs. J Vet Intern Med. 2010;24(4):850–854. doi:10.1111/j.1939-1676.2010.0517.x

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Kellum HB, Stepien RL. Sildenafil citrate therapy in 22 dogs with pulmonary hypertension. J Vet Intern Med. 2007;21(6):1258–1264. doi:10.1111/j.1939-1676.2007.tb01947.x

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Kempf J, Lewis F, Reusch CE, Kook PH. High-resolution manometric evaluation of the effects of cisapride and metoclopramide hydrochloride administered orally on lower esophageal sphincter pressure in awake dogs. Am J Vet Res. 2014;75(4):361–366. doi:10.2460/ajvr.75.4.361

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Ullal TV, Kass PH, Conklin JL, Belafsky PC, Marks SL. High-resolution manometric evaluation of the effects of cisapride on the esophagus during administration of solid and liquid boluses in awake healthy dogs. Am J Vet Res. 2016;77(8):818–827. doi:10.2460/ajvr.77.8.818

    • Crossref
    • Search Google Scholar
    • Export Citation

Advertisement