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Furosemide Recommendations

Grade

MMVD (Stabilisation)

ACVIM MMVD Stage C (Hospital Stabilisation) 

Dosing > Patient Identification and Preparation > Additional Medications and Nursing > Patient Support > Additional Procedures

Initial Dosing

  • Bolus Loading: 2-5 mg/kg, IV.

  • IV Stabilisation: Repeat 2-5 mg/kg, q1-2h as a slow IV injection until the respiratory rate and respiratory character improve.

  • CRI Stabilisation: 0.66-1 mg/kg/h after an IV bolus of 2-5 mg/kg as above (Ohad, et al. 2018).


Acute Stage C MMVD cases generally require hospital admission for appropriate care.  Combinations of several medications and procedures are often employed in a suitable nursing environment.


  • Identfication: For ACVIM MMVD Stage C identfication advice  see patient identification and preparation below.

  • Outpatient Dosing: For ACVIM MMVD Stage C outpatient dosing, see Indication 2.

Subsequent Dosing

  • IV Maintenance: 1-2 mg/kg IV/IM q6-8h is used for maintenance during hospitalisation, with a maximum advised daily dose of 12 mg/kg (DeFrancesco, 2013; Keene et al., 2019).

Patient Identification and Preparation

Patients with unstable MMVD stage C will typically exhibit the following clinical signs: tachypnea, restlessness, respiratory distress, cough, heart murmur, lethargy, syncope or episodic weakness, abdominal distention (dog), and/or partial to complete anorexia. Echocardiography with Doppler studies identifies dogs with MMVD that have advanced to Stages C and D (DeFrancesco, 2013; Keene et al., 2019).


Patients with unstable MMVD stage C are weighed and admitted through a standard practice-specific procedure. Informed consent is taken for medical investigation and stabilisation, including diagnostic imaging, bloodwork, and possible additional therapeutic measures such as cavitary centesis.  


  • Patients are cannulated.

  • Patients are placed into a suitable therapeutic oxygen-rich environment. 

  • Many patients will benefit from some form of anxiolytic or sedative.

Additional Medications and Nursing

  • Dobutamine CRI: 2.5-10 μg/kg/min may improve the left ventricular function in patients who fail to respond adequately to diuretics.

  • Sodium Nitroprusside CRI:  1 to 15 μg/kg/min for up to 48 h may stabilise life-threatening, poorly responsive pulmonary oedema (Sabbah et al., 1993).

  • Nitroglycerin (Glyceryl Trinitrate): 0.25–1.0 cm of a 2% transdermal ointment q 8–24 h for 1–2 d.

  • Anxiolytic: Typically an opiate ( e.g. Methadone, Butorphanol or Buprenorphine) or an opiate-based neuroleptic combination.

Patient Support

  • Oxygen: Provide an oxygen chamber with minimal patient restraint, in preference to an oxygen mask or flow by oxygen.

Additional Procedures

Additional procedures are facility, clinician and patient-specific.


  • Cavitary Centesis: Abdominal paracentesis and thoracentesis may be required to relieve respiratory distress or discomfort.  

Recommendation Strength (Proposed)

  • Strong: The results of PICO analysis and delphi survey will be included here.

Therapeutics

​

ACVIM MMVD Stage 

We recommend the ACVIM consensus guidelines for disease staging and the use of furosemide in canine heart failure (Keene et al., 2019).

Sole Use

  • Chronic Diuretic monotherapy in the management of cardiac failure should be avoided, as patients receiving diuretics alone may deteriorate more rapidly than those receiving other treatment modalities.

Multimodal Use

  • We recommend following ACVIM and similar consensus guidelines for disease staging and using Furosemide in MMVD-related canine heart failure.  This usually involves additional Pimobendan.  Additional medications may differ during the stabilisation and maintenance of MMVD Stage C, as detailed in this monograph. 

Treatment Goals 

To maintain patient comfort at each stage of MMVD and prolong the length and quality of life of MMVD patients at each ACVIM stage.


Assessing any improved quality of life of patients with MMVD receiving Furosemide currently relies upon a subjective, case-by-case judgement; however, there is a clear case for a future focus on the cost and quantity of beneficial quality-adjusted life years (QALYs) achieved through specific Furosemide protocols (Cohen et al., 2018; Neumann et al., 2018, 2016; Neumann and Cohen, 2018; Neumann and Kim, 2023; P Neumann and Cohen, 2015). 


  • Organ Level: Treatment aims to reduce oedema and ascites, improve cardiac function in canine patients with MMVD, and slow, halt, or reverse the progression and stage of MMVD.

  • Patient Level: The treatment objective is to increase the quality and quantity of survival time for patients with MMVD and to slow, halt or reverse the disease progression. 

  • Client level:  The goal of treatment is to offer a value-for-money increase in beneficial quality-adjusted life years (QALYs)  to clients with dogs experiencing MMVD.

Treatment End Point 

  • The duration of treatment is unlimited, so it is usually lifelong until death or euthanasia (Keene et al., 2019).

Therapeutic Monitoring

Renal function, hydration status and serum electrolytes status should be monitored (Serum electrolytes, BUN, creatinine, SDMA +/- glucose if diabetic):


  • When treatment is commenced

  • 24-48h post commencement

  • 24-48h post-dose adjustment

  • If adverse events occur.


Additionally, patients will benefit from regular physical assessments covering. Heart rate and quality, respiratory rate and effort (resting and sleeping), blood pressure, signs associated with oedema, thirst, urine output and weight.

Efficacy Profile

Furosemide is an effective high-ceiling small animal loop diuretic (Abbott and Kovacic, 2008; Adin et al., 2017, 2003; Berg and Loew, 1977; Cohen et al., 1976; Ding et al., 2016; Harada et al., 2015; Hori et al., 2010, 2007; Lee et al., 1986; Ochoa et al., 2006; Raisbeck et al., 1983; Sayer et al., 2009; Scruggs and Rishniw, 2013; Uechi et al., 2003).


Several studies compare its action to torasemide, which is not available as an injectable product in the UK at the time of writing (Hori et al., 2007; Uechi et al., 2003).

  • Potency: Torsemide is 10 to 20 times more potent as a loop diuretic than Furosemide.

  • Bioavailability: Torsemide has higher bioavailability and a longer duration of action than Furosemide, with reduced comparative calciuresis and kaliuresis.

Alternative Products 

Other Diuretics

Alternative Protocols

  • VCI recommends the ACVIM protocols for MMVD. Where additional material is identified, it supplements existing ACVIM consensus protocols.

Evidence

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1 Species-Specific Evidence Review 

  1. DeFrancesco, T.C., 2013. Management of Cardiac Emergencies in Small Animals. Veterinary Clinics of North America: Small Animal Practice 43, 817–842. https://doi.org/10.1016/j.cvsm.2013.03.012

  2. Keene, B.W., Atkins, C.E., Bonagura, J.D., Fox, P.R., Häggström, J., Fuentes, V.L., Oyama, M.A., Rush, J.E., Stepien, R., Uechi, M., 2019. ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs. J Vet Intern Med 33, 1127–1140. https://doi.org/10.1111/jvim.15488

  3. Suzuki, S., Ishikawa, T., Hamabe, L., Aytemiz, D., Huai-Che, H., Fukushima, R., Machida, N., Tanaka, R., 2011. The Effect of Furosemide on Left Atrial Pressure in Dogs with Mitral Valve Regurgitation. Journal of Veterinary Internal Medicine 25, 244–250. https://doi.org/10.1111/j.1939-1676.2010.0672.x

2 Condition-Specific Evidence Review

  1. DeFrancesco, T.C., 2013. Management of Cardiac Emergencies in Small Animals. Veterinary Clinics of North America: Small Animal Practice 43, 817–842. https://doi.org/10.1016/j.cvsm.2013.03.012

  2. Keene, B.W., Atkins, C.E., Bonagura, J.D., Fox, P.R., Häggström, J., Fuentes, V.L., Oyama, M.A., Rush, J.E., Stepien, R., Uechi, M., 2019. ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs. J Vet Intern Med 33, 1127–1140. https://doi.org/10.1111/jvim.15488

  3. Suzuki, S., Ishikawa, T., Hamabe, L., Aytemiz, D., Huai-Che, H., Fukushima, R., Machida, N., Tanaka, R., 2011. The Effect of Furosemide on Left Atrial Pressure in Dogs with Mitral Valve Regurgitation. Journal of Veterinary Internal Medicine 25, 244–250. https://doi.org/10.1111/j.1939-1676.2010.0672.x

3 Substance-Specific Evidence Review

  1. Abbott, L.M., Kovacic, J., 2008. The pharmacologic spectrum of furosemide. Journal of Veterinary Emergency and Critical Care 18, 26–39. https://doi.org/10.1111/j.1476-4431.2007.00267.x

  2. Adin, D., Atkins, C., Papich, M., DeFrancesco, T., Griffiths, E., Penteado, M., Kurtz, K., Klein, A., 2017. Furosemide continuous rate infusion diluted with 5% dextrose in water or hypertonic saline in normal adult dogs: a pilot study. Journal of Veterinary Cardiology 19, 44–56. https://doi.org/10.1016/j.jvc.2016.09.004

  3. Adin, D.B., Taylor, A.W., Hill, R.C., Scott, K.C., Martin, F.G., 2003. Intermittent Bolus Injection versus Continuous Infusion of Furosemide in Normal Adult Greyhound Dogs. Journal of Veterinary Internal Medicine 17, 632–636. https://doi.org/10.1111/j.1939-1676.2003.tb02493.x

  4. Branch, R.A., 1983. Role of binding in distribution of furosemide: where is nonrenal clearance? Fed Proc 42, 1699–1702.

  5. Brown, R.D., 1981. Comparative Acute Cochlear Toxicity of Intravenous Bumetanide and Furosemide in the Purebred Beagle. The Journal of Clinical Pharmacology 21, 620–627. https://doi.org/10.1002/j.1552-4604.1981.tb05674.x

  6. Chan, C.M., Frimberger, A.E., Moore, A.S., 2016. Incidence of sterile hemorrhagic cystitis in tumor-bearing dogs concurrently treated with oral metronomic cyclophosphamide chemotherapy and furosemide: 55 cases (2009–2015). Journal of the American Veterinary Medical Association 249, 1408–1414. https://doi.org/10.2460/javma.249.12.1408

  7. Cohen, M.R., Hinsch, E., Vergona, R., Ryan, J., Kolis, S.J., Schwartz, M.A., 1976. A comparative diuretic and tissue distribution study of bumetanide and furosemide in the dog. J Pharmacol Exp Ther 197, 697–702.

  8. Ding, D., Liu, H., Qi, W., Jiang, H., Li, Y., Wu, X., Sun, H., Gross, K., Salvi, R., 2016. Ototoxic effects and mechanisms of loop diuretics. J Otol 11, 145–156. https://doi.org/10.1016/j.joto.2016.10.001

  9. Fisk, A., Londoño, L., Carrera-Justiz, S., Buckley, G., 2019. Cochleotoxicity and acute kidney injury secondary to parenteral gentamicin administration in a dog. Can Vet J 60, 976–980.

  10. Harada, K., Ukai, Y., Kanakubo, K., Yamano, S., Lee, J., Kurosawa, T.A., Uechi, M., 2015. Comparison of the diuretic effect of furosemide by different methods of administration in healthy dogs. Journal of Veterinary Emergency and Critical Care 25, 364–371. https://doi.org/10.1111/vec.12301

  11. Hori, Y., Ohshima, N., Kanai, K., Hoshi, F., Itoh, N., Higuchi, S., 2010. Differences in the Duration of Diuretic Effects and Impact on the Renin-Angiotensin-Aldosterone System of Furosemide in Healthy Dogs. J. Vet. Med. Sci. 72, 13–18. https://doi.org/10.1292/jvms.09-0259

  12. Lee, M.G., Li, T., Chiou, W.L., 1986. Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of furosemide. Biopharmaceutics & Drug Disposition 7, 537–547. https://doi.org/10.1002/bdd.2510070603

  13. Ochoa, P.G., Arribas, M.T.V., Mena, J.M., Pérez, M.G., 2006. Cutaneous adverse reaction to furosemide treatment: new clinical findings. Can Vet J 47, 576–578.

  14. Raisbeck, M.F., Hewitt, W.R., McIntyre, W.B., 1983. Fatal nephrotoxicosis associated with furosemide and gentamicin therapy in a dog. J Am Vet Med Assoc 183, 892–893.

  15. Sayer, M. b., Atkins, C. e., Fujii, Y., Adams, A. k., DeFrancesco, T. c., Keene, B. w., 2009. Acute Effect of Pimobendan and Furosemide on the Circulating Renin-Angiotensin-Aldosterone System in Healthy Dogs. Journal of Veterinary Internal Medicine 23, 1003–1006. https://doi.org/10.1111/j.1939-1676.2009.0367.x

  16. Scruggs, S.M., Rishniw, M., 2013. Dermatologic adverse effect of subcutaneous furosemide administration in a dog. J Vet Intern Med 27, 1248–1250. https://doi.org/10.1111/jvim.12156

  17. Uechi, M., Matsuoka, M., Kuwajima, E., Kaneko, T., Yamashita, K., Fukushima, U., Ishikawa, Y., 2003. The Effects of the Loop Diuretics Furosemide and Torasemide on Diuresis in Dogs and Cats. J. Vet. Med. Sci. 65, 1057–1061. https://doi.org/10.1292/jvms.65.1057

4 Efficacy Review

  1. Adin, D., Atkins, C., Papich, M., DeFrancesco, T., Griffiths, E., Penteado, M., Kurtz, K., Klein, A., 2017. Furosemide continuous rate infusion diluted with 5% dextrose in water or hypertonic saline in normal adult dogs: a pilot study. Journal of Veterinary Cardiology 19, 44–56. https://doi.org/10.1016/j.jvc.2016.09.004

  2. Adin, D.B., Taylor, A.W., Hill, R.C., Scott, K.C., Martin, F.G., 2003. Intermittent Bolus Injection versus Continuous Infusion of Furosemide in Normal Adult Greyhound Dogs. Journal of Veterinary Internal Medicine 17, 632–636. https://doi.org/10.1111/j.1939-1676.2003.tb02493.x

  3. Harada, K., Ukai, Y., Kanakubo, K., Yamano, S., Lee, J., Kurosawa, T.A., Uechi, M., 2015. Comparison of the diuretic effect of furosemide by different methods of administration in healthy dogs. Journal of Veterinary Emergency and Critical Care 25, 364–371. https://doi.org/10.1111/vec.12301

  4. Hori, Y., Ohshima, N., Kanai, K., Hoshi, F., Itoh, N., Higuchi, S., 2010. Differences in the Duration of Diuretic Effects and Impact on the Renin-Angiotensin-Aldosterone System of Furosemide in Healthy Dogs. J. Vet. Med. Sci. 72, 13–18. https://doi.org/10.1292/jvms.09-0259

  5. Hori, Y., Takusagawa, F., Ikadai, H., Uechi, M., Hoshi, F., Higuchi, S., 2007. Effects of oral administration of furosemide and torsemide in healthy dogs. Am J Vet Res 68, 1058–1063. https://doi.org/10.2460/ajvr.68.10.1058

  6. Lee, M.G., Li, T., Chiou, W.L., 1986. Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of furosemide. Biopharmaceutics & Drug Disposition 7, 537–547. https://doi.org/10.1002/bdd.2510070603

  7. Sayer, M. b., Atkins, C. e., Fujii, Y., Adams, A. k., DeFrancesco, T. c., Keene, B. w., 2009. Acute Effect of Pimobendan and Furosemide on the Circulating Renin-Angiotensin-Aldosterone System in Healthy Dogs. Journal of Veterinary Internal Medicine 23, 1003–1006. https://doi.org/10.1111/j.1939-1676.2009.0367.x

  8. Uechi, M., Matsuoka, M., Kuwajima, E., Kaneko, T., Yamashita, K., Fukushima, U., Ishikawa, Y., 2003. The Effects of the Loop Diuretics Furosemide and Torasemide on Diuresis in Dogs and Cats. J. Vet. Med. Sci. 65, 1057–1061. https://doi.org/10.1292/jvms.65.1057

Supplementary Information 1 | UK SPC Links

  1. Dimazon 50 mg/ml Solution for Injection [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/current/search-results (accessed 12.28.23).

  2. Frusedale 40 mg Oral Tablets [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A003210 (accessed 12.28.23).

  3. Frusemide 40 mg Tablets [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A005945 (accessed 12.28.23).

  4. Furosemide 10mg/ml Oral Solution - Summary of Product Characteristics (SmPC) - (emc) [WWW Document], n.d. URL https://www.medicines.org.uk/emc/product/2460/smpc#gref (accessed 12.29.23).

  5. Furosemide 20 mg/5 ml Oral Solution - Summary of Product Characteristics (SmPC) - (emc) [WWW Document], n.d. URL https://www.medicines.org.uk/emc/product/4576/smpc#gref (accessed 12.29.23).

  6. Furosemide Tablets BP (Vet) 20 mg [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/current/search-results (accessed 12.28.23).

  7. Furosemide Tablets BP (Vet) 40 mg [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A003335 (accessed 12.28.23).

  8. Furosivet 20 mg Tablets for Dogs and Cats [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010184 (accessed 12.28.23).

  9. Furosoral 10 mg Tablets for Cats and Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009114 (accessed 12.28.23).

  10. Furosoral 40 mg Tablets for Cats and Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009115 (accessed 12.28.23).

  11. Libeo 40 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008670 (accessed 12.28.23).

Supplementary Information 2 | QALYs

  1. Cohen, J., Neumann, P., Wong, J., 2018. A Call for Open-Source Cost-Effectiveness Analysis. Annals of internal medicine 168. https://doi.org/10.7326/L17-0695

  2. Neumann, P., Anderson, J., Panzer, A., Pope, E., D’Cruz, B., Kim, D., Cohen, J., 2018. Comparing the cost-per-QALYs gained and cost-per-DALYs averted literatures. Gates open research 2. https://doi.org/10.12688/gatesopenres.12786.2

  3. Neumann, P., Cohen, J., 2018. QALYs in 2018-Advantages and Concerns. JAMA 319. https://doi.org/10.1001/jama.2018.6072

  4. Neumann, P., Thorat, T., Zhong, Y., Anderson, J., Salem, M., Sandberg, E., Saret, C., Wilkinson, C., Cohen, J., 2016. A Systematic Review of Cost-Effectiveness Studies Reporting Cost-per-DALY Averted. PloS one 11. https://doi.org/10.1371/journal.pone.0168512

  5. Neumann, P.J., Kim, D.D., 2023. Cost-effectiveness Thresholds Used by Study Authors, 1990-2021. JAMA 329, 1312–1314. https://doi.org/10.1001/jama.2023.1792

  6. P Neumann, Cohen, J., 2015. Measuring the Value of Prescription Drugs. The New England journal of medicine 373. https://doi.org/10.1056/NEJMp1512009

Supplementary Information 3 | 1317822

  • Some material recommended by the [Primer] author, was taken from SPCs or extrapolated from veterinary and pharmacology texts, or is the authors opinion.


Monograph Details

​

Evidence Development

Evidence Search and Search Engines

  1. Stuart McArthur B Vet Med MRCVS

Evidence Analysis and Zotero database

  1. Stuart McArthur B Vet Med MRCVS

Monograph Development

Primary Monograph Author(s)

  1. Stuart McArthur B Vet Med MRCVS

Primary Monograph Editor(s)

  1. John Doe MRCVS 

  2. Jane Doe DVM

Consensus Development

Suitability Workgroup (A-Z)

  1. John Doe MRCVS 

  2. Jane Doe DVM

Safety Workgroup (A-Z)

  1. John Doe MRCVS 

  2. Jane Doe DVM

Posology Workgroup (A-Z)

  1. John Doe MRCVS 

  2. Jane Doe DVM

Efficacy Workgroup (A-Z)

  1. John Doe MRCVS 

  2. Jane Doe DVM

Monograph Quality Workgroup (A-Z)

  1. John Doe MRCVS 

  2. Jane Doe DVM

Review Date(s) 

  • Last Review Date: 18.01.24

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