Content continues after advertisement

Congenital Portosystemic Shunt in a Dog

Sophie Eiger, VMD, University of Florida

W. Alex Fox-Alvarez, DVM, MS, DACVS-SA, Veterinary Surgicenter Gainesville, Florida 

Pharmacology & Medications

|March 2022|Peer Reviewed

Sign in to Print/View PDF

Millie, a 10-month-old spayed Yorkshire terrier, is presented for evaluation of a suspected congenital portosystemic shunt (PSS). She has a history of vomiting and diarrhea, occasional stranguria, polyuria, polydipsia, and postprandial lethargy. Millie was recently spayed, and the referral noted a prolonged anesthetic recovery, prompting further investigation. 

Physical examination is unremarkable, with the exception of a coarse hair coat and BCS of 3/9. CBC reveals a mild microcytic, normochromic, nonregenerative anemia. Serum chemistry profile reveals moderate increases in ALT and AST, mild hypoalbuminemia, mildly decreased BUN, mild hypoglycemia, and mild hypocholesterolemia. Urinalysis demonstrates a urine specific gravity of 1.006 and ammonium biurate crystalluria. Fasting and postprandial serum bile acids are significantly elevated. 

Millie is placed on preoperative medical therapy and a protein-restricted diet and is referred for further diagnostics and surgery.

After 2 weeks, CT angiography is performed, and a splenocaval shunt (Figure 1) and multiple cystoliths are revealed. Exploratory laparotomy is performed, the splenocaval shunt is identified, and an ameroid ring constrictor is placed to achieve gradual occlusion (Figure 2). A liver biopsy is obtained, and a routine cystotomy is performed to remove the cystoliths. All samples are submitted for analysis. 

Postattenuation neurologic signs are seen postoperatively, and Millie has a seizure. Medical intervention is initiated; neurologic signs resolve. She is discharged 2 days postoperatively on continued medical therapy and will return for a 2-week follow-up to have the incision checked. Additional follow-ups to monitor response to therapy are planned 1 and 3 months postoperatively for repeat blood work.

Based on the information provided, how would you grade the following drugs and why?

Do Not Use Proceed with Caution Safe

The following represents the best responses based on drug metabolism, pharmacokinetics, species, diagnostic differentials, clinical and laboratory data, and other pertinent findings.

Levetiracetam

Correct ResponseSafeHepatic encephalopathy is a neuropsychiatric syndrome that occurs if >70% of hepatic function is lost.1,2 In veterinary patients, common signs include lethargy, depression, stupor, head pressing, blindness, seizures, muscle function abnormalities, and coma.3 Because of the hepatic shunting associated with PSS, toxic substances accumulate in systemic circulation and can cause neurologic disturbances.2,4 Antiepileptic medications have previously been used to address hepatic encephalopathy and seizures.

Levetiracetam is a broad-spectrum anticonvulsant that appears to inhibit excitatory neurotransmitter release by binding to SV2A, a synaptic vesicle protein.5-7 Because protein binding is minimal and levetiracetam is primarily eliminated through the kidneys rather than the liver, levetiracetam is safe to use in patients with PSS.8

The use of levetiracetam to prevent postattenuation seizures is controversial. One retrospective study demonstrated that levetiracetam administered preoperatively at 20 mg/kg PO every 8 hours for a minimum of 24 hours significantly decreased the risk for postoperative seizures and death in dogs undergoing surgical attenuation of extrahepatic congenital PSS with ameroid ring constrictors.6 Other studies, however, demonstrated no significant difference in the incidence of postattenuation seizures in dogs that do or do not receive levetiracetam.9,10 Although levetiracetam may not prevent seizures, its liver-sparing metabolic characteristics make it an acceptable antiepileptic medication to use in patients with PSS.

Lactulose

Correct ResponseSafeAmmonia is produced by GI microbiota and is typically converted to urea and glutamine via the urea cycle in the normal liver.4 The abnormal blood flow associated with PSS results in ammonia accumulation.

Lactulose is an ammonia detoxicant, osmotic, and laxative commonly used as an adjunctive treatment to reduce ammonia blood levels associated with hepatic encephalopathy.11,12 Lactulose can be administered orally or via high colonic enemas and is metabolized by colonic bacteria, resulting in the formation of carbon dioxide and lactic, formic, and acetic acids.13 This acidic environment promotes the conversion of ammonia (NH3) to ammonium (NH4+), which is not readily absorbed and becomes ion-trapped and expelled in the feces.

Free fatty acid production also increases osmotic pressure in the bowel, creating a laxative effect and acidifying the colonic microenvironment. Osmotic effects can result in catharsis, reducing fecal transit time and intestinal exposure to bacteria and their ammonia products.4

Metronidazole

Correct ResponseProceed with CautionMetronidazole is a concentration-dependent bactericidal drug commonly used in patients with PSS.11 The goal of antibiotic therapy in patients with PSS is to decrease the intestinal load of urease-producing bacteria.2,4,11 Although metronidazole is often included in the medical management plan for patients with PSS, it is extremely important to adhere to appropriate administration practices and evaluate for signs of toxicity.14,15 Neurologic toxicity may occur after acute high doses of metronidazole, even in healthy dogs, and has been reported at appropriate doses in patients with PSS. Neurologic signs related to metronidazole administration may be difficult to distinguish from hepatic encephalopathy.

Ampicillin

Correct ResponseSafeAmpicillin is a time-dependent, bactericidal agent used to decrease intestinal loads of urease-producing bacteria.16 Although its anaerobic spectrum is not as wide as metronidazole, ampicillin lacks the potential for neurotoxicity. Amoxicillin is also effective, but ampicillin has lower oral bioavailability and is preferrable to minimize systemic absorption. For appropriate antibiotic stewardship, broad-spectrum, potentiated beta-lactams (eg, amoxicillin/clavulanate) should not be used in place of their narrower-spectrum analogs.

Benzodiazepines

Correct ResponseProceed with CautionPostoperative seizures develop in 3% to 18% of dogs after shunt attenuation and are most commonly seen in small-breed dogs with extrahepatic shunts.4,6,9,10,17-21 The cause of postoperative seizures is unknown; however, potential causes include imbalances in excitatory and inhibitory neurotransmitters or decreases in endogenous inhibitory CNS benzodiazepine agonist levels.4,22 Benzodiazepines are generally accepted as first-line treatment for postattenuation status epilepticus.1,23 Intravenous diazepam contains a propylene glycol carrying agent that requires hepatic metabolism; midazolam may be a better choice for acute seizure control than is diazepam.4

Controversy exists regarding the use of benzodiazepines to control seizures in patients with PSS. Intrinsic benzodiazepine-like compounds are hypothesized to be involved in hepatic encephalopathy.3 Accordingly, in humans, flumazenil has been used to improve mental status24; however, potential for similar improvements have not been evaluated in veterinary patients with hepatic encephalopathy. A study also demonstrated elevated concentrations of endogenous benzodiazepine receptor ligands in dogs with congenital PSS when compared with control dogs.1

Although benzodiazepines are clinically effective in patients with PSS that experience seizures, further research is required to determine the role of benzodiazepines in treating hepatic encephalopathy.

Propofol

Correct ResponseSafePropofol is a short-acting, injectable sedative-hypnotic agent frequently used for anesthetic induction in patients with PSS. Many commonly used anesthetic drugs are primarily metabolized by hepatic microsomal enzymes; therefore, hepatic dysfunction with PSS may result in prolonged half-lives and effects of administered anesthetic doses.25

As propofol may have extrahepatic metabolic sites, it is the most commonly used induction agent for patients with hepatic dysfunction25; however, because it is a protein-bound drug, lower total doses may be necessary in patients with PSS that have hypoalbuminemia. In addition, boluses and CRI are useful for the treatment of postattenuation seizures.22,26

Propofol is believed to be beneficial for the treatment of status epilepticus because of its gamma-aminobutyric acid activity at a different site from benzodiazepines.23

Phenobarbital

Correct ResponseProceed with CautionPhenobarbital is an antiepileptic barbiturate used to treat postoperative seizures22,23 that is hepatically metabolized and has been shown to cause hepatic injury after long-term administration in dogs.27 Phenobarbital has a lower lipid solubility and may take up to 30 minutes to reach therapeutic concentrations; therefore, benzodiazepines should be used instead as a first-line treatment for status epilepticus.4

Carprofen

Correct ResponseDo Not UseNSAIDs (eg, carprofen) are commonly used to treat acute and chronic pain. All NSAIDs have the potential to cause hepatic injury (intrinsically or idiosyncratically) and may impair coagulation and hemostasis by impacting platelet aggregation and clot formation.24 NSAIDs are also a risk factor for GI ulceration because of their effect on gastric mucosal integrity and prostaglandin synthesis.28 Because GI signs (eg, vomiting, diarrhea, anorexia, pica, GI bleeding) occur in ≈30% of dogs with PSS, NSAIDs may worsen these signs.4

One study found a 38.5% mortality rate in dogs with intrahepatic shunts treated with NSAIDs perioperatively, compared with 2.4% in dogs not treated with NSAIDs.28 All dogs in the study that died because of confirmed or suspected gastroduodenal ulcerations received NSAIDs postoperatively.28

NSAIDs should be avoided in patients with hepatic dysfunction and PSS because patients with PSS are predisposed to developing gastric ulceration and there are reported increases in mortality.

After successful treatment, NSAIDs can be considered in patients with an extrahepatic PSS but should be used with caution in patients with an intrahepatic PSS, even after surgical correction, due to the lifelong risk for GI ulceration.

Omeprazole

Correct ResponseSafeProton-pump inhibitors (eg, omeprazole) are indicated in dogs with PSS because of the high prevalence of concurrent GI signs. Omeprazole and other substituted benzimidazole proton-pump inhibitors are the most potent antisecretory drugs and are reported to reduce gastric acid secretion by 80% to 95%.29 Studies regarding intrahepatic PSS have demonstrated that up to 21% of dogs have lifelong risk for GI ulceration associated with significantly shorter survival times.30 In dogs undergoing treatment for intrahepatic PSS prior to antacid therapy, 50% of deaths were attributable to GI bleeding; lifelong antacid therapy reduced this rate to 4%.30

Although the reported rates of GI signs in extrahepatic PSS are lower, it is reasonable to use proton-pump inhibitors in patients with extrahepatic PSS that also have a history of ulceration, melena, or GI signs.

S-Adenosyl-Methionine

Correct ResponseSafeS-adenosyl-methionine (SAMe), an endogenous coenzyme, is composed of an adenosine triphosphate and methionine, a sulfur-containing amino acid.12 SAMe is necessary for transmethylation, transsulfuration, and decarboxylation reactions, as well as the production of glutathione, which is a crucial hepatic antioxidant.12,31 Because of the hygroscopic nature of SAMe and known variations in product bioavailability, formulations should be obtained from reputable manufacturers.31 Although there is minimal veterinary evidence-based information to substantiate efficacy of this hepatoprotective supplement, it may be beneficial as adjunctive treatment in dogs with PSS based on its safety profile, anecdotal use, and extensive preclinical studies and use in human hepatic diseases.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Clinician's Brief may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.

Podcasts

Clinician's Brief:
The Podcast
Listen as host Alyssa Watson, DVM, talks with the authors of your favorite Clinician’s Brief articles. Dig deeper and explore the conversations behind the content here.
Clinician's Brief provides relevant diagnostic and treatment information for small animal practitioners. It has been ranked the #1 most essential publication by small animal veterinarians for 9 years.*

*2007-2017 PERQ and Essential Media Studies

© 2023 Educational Concepts, L.L.C. dba Brief Media ™ All Rights Reserved. Terms & Conditions | DMCA Copyright | Privacy Policy | Acceptable Use Policy