Coagulation profiles in dogs with congenital portosystemic shunts before and after surgical attenuation

BACKGROUND: Serious postoperative hemorrhage has been reported in dogs after closure of congenital portosystemic shunts (CPS). HYPOTHESIS: In dogs with portosystemic shunting, low coagulation factor activity is responsible for coagulopathy, which can cause complications after surgery. ANIMALS: Thirty-four dogs with CPS and 39 healthy dogs. METHODS: In a prospective study, coagulation times, platelet count, and the activity of 8 coagulation factors were measured in dogs before and after surgical shunt attenuation and in 31 healthy dogs. The effect of abdominal surgery on hemostasis was determined at ovariectomy in 8 healthy dogs. RESULTS: Dogs with CPS had lower platelet counts, lower activity of factors II, V, VII, and X, and increased factor VIII and activated partial thromboplastin time (APTT) compared to healthy dogs. After surgical attenuation, dogs with CPS had decreased platelet counts and activity of factors I, II, V, VII, IX, X, and XI and a prolonged prothrombin time (PT). Ovariectomy resulted in decreased activity of factors VII and X. Six weeks after surgery, portosystemic shunting persisted in 9 of 30 dogs, with no improvement of hemostatic values. CPS dogs without shunting had improved coagulation times and increased activity of factors II, V, VII, and X. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with CPS have lower activity of clotting factors compared to healthy dogs, resulting in a prolonged APTT. Surgical attenuation of the shunt results in increased abnormalities in coagulation times and factors immediately after surgery. Hemostasis is normalized after complete recovery of shunting after attenuation, in contrast to dogs with persistent shunting.     

Hepatic gene expression and plasma albumin concentration related to outcome after attenuation of a congenital portosystemic shunt in dogs

In dogs with a congenital portosystemic shunt (CPSS), the outcome after CPSS attenuation is difficult to predict but is most likely related to hepatic and vascular proliferation that follows the attenuation. The aim of this study was to evaluate the prognostic value of shunt localization (extrahepatic vs. intrahepatic), plasma albumin concentration and hepatic mRNA expression of 19 genes involved in hepatic and vascular growth. The study population consisted of 48 dogs that were referred for surgical ligation of a single intrahepatic or extrahepatic CPSS. Gene expression was measured in intraoperatively sampled hepatic tissue with quantitative real-time PCR. Albumin, methionine adenosyltransferase 2α (MAT2α) and HGF activator (HGFac) were positively associated with complete recovery after CPSS attenuation using multivariate statistical analyses. Individual outcome could be correctly predicted in 83% of dogs using albumin, MAT2α and HGFac as high or low values compared to cut-off values of 19.5 g/L, 0.457 and 0.974, respectively. These variables predicted outcome after CPSS ligation better than shunt localization or albumin alone. Other evaluated gene products were not correlated with outcome.     

Postattenuation neurologic signs after surgical attenuation of congenital portosystemic shunts in dogs: A review

The development of postattenuation neurologic signs (PANS) is a poorly understood and potentially devastating complication after surgical attenuation of congenital portosystemic shunts in dogs. Postattenuation neurologic signs include seizures but also more subtle neurologic signs such as depression, behavioral changes, tremors, and twitching. They most commonly occur within 7 days postoperatively and are typically unrelated to hyperammonemia, hypoglycemia, or electrolyte disturbances. This narrative review summarizes the findings of 50 publications from 1988-2020 that report occurrence of PANS. While most published reports included only dogs affected by postattenuation seizures (PAS), others included dogs with any form of PANS. Overall, PANS (including PAS) affected 1.6%-27.3% of dogs, whereas incidence of PAS ranged from 0%-18.2%. The etiology of PANS remains unknown; however, several theories have been proposed. Risk factors include preoperative hepatic encephalopathy, increasing age, and possibly certain breeds and extrahepatic shunt morphology. There is increasing evidence that prophylactic antiepileptic drugs do not prevent PANS. Treatment is centered around controlling neurologic signs with antiepileptic drugs and providing supportive intensive care. The 30-day survival rate in studies that included a minimum of four dogs affected by PANS was 0%-100% (median, 50.0%) and 0%-75.0% (median, 37.5%) for those with PAS. Mortality associated with PANS was typically related to occurrence of generalized seizure activity. Prognostic factors positively associated with short-term survival included having a history of preoperative seizures and development of focal seizures only. If affected dogs survived to discharge, survival for several years was possible, and the majority of neurologic signs manifested as part of the phenomenon of PANS appeared to resolve.     

Fast resolution of hypercortisolism in dogs with portosystemic encephalopathy after surgical shunt closure

The aim of this study was to investigate whether hypercortisolism in dogs with congenital portosystemic shunts disappeared after surgical closure of the shunts concomitantly with recovery from hepatic encephalopathy. We examined 22 dogs before and four weeks after partial surgical closure of a single, large congenital portosystemic shunt (PSS). Parameters measured to characterise the basal activity of the pituitary-adrenal axis were the cortisol:creatinine (c/c) ratio in home-sampled urine and total and free cortisol in plasma. The binding characteristics of cortisol binding globulin (CBG) in pooled pre- and postoperative plasma were also determined. Ammonia and bile acid concentrations were measured in plasma to characterise the liver perfusion and function. Clinical symptoms relevant to liver function, cortisol excess, and hepatic encephalopathy were recorded semiquantitatively using a standardized questionnaire. The dogs had hypercortisolism before surgery, which had normalized four weeks later. The pre- and postoperative concentrations (means +/- SEM) were, respectively, 238+/-45 nM and 126+/-19 nM for total cortisol, 15.5+/-2.6 nM and 8.4+/-1.3 nM for free cortisol in plasma, 13.4+/-4.3 x 10(-6) and 3.9+/-0.4 x 10(-6) for c/c in urine. The pre- and postoperative Bmax values of CBG were 41 and 79, and Kd values were 3.8 and 5.5. The concentrations of ammonia were 217+/-23 microM and 32+/-3.1 microM, and of bile acids 1 10+/-33 and 11.1+/-2.0 microM, respectively. We conclude that there is a close relation between portosystemic encephalopathy and hypercortisolism in dogs with PSS and that both deviations resolve completely within four weeks of closure of the shunt.     

The effect of neuraxial morphine on postoperative pain in dogs after extrahepatic portosystemic shunt attenuation

ObjectiveTo investigate the analgesic effect of epidural morphine after surgical extrahepatic portosystemic shunt (EHPSS) attenuation.Study designRandomized clinical trial.AnimalsA total of 20 dogs with a congenital EHPSS.MethodsDogs were randomly allocated to be given either a single epidural dose of 0.2 mg kg^–1 preservative-free morphine (group M) or not (group C) before surgery. All dogs were administered 0.3 mg kg^–1 methadone intravenously (IV) as preanaesthetic medication. Pain scores were determined every 2 hours for the first 24 hours postoperatively using the short-form Glasgow Composite Measure Pain Scale (GCMPS-SF). Dogs with a GCMPS-SF pain score >4/20 or >5/24 received 0.1 mg kg^–1 methadone IV as rescue analgesia and were reassessed 30 minutes later. If more than three doses of methadone were administered in a 2 hour period, alternative pain relief was provided and a treatment failure recorded. The GCMPS-SF pain scores and number of rescue analgesia injections were analysed over 24 hours. The last observation carried forward method was applied in case of treatment failure. Food consumption and time to first urination were recorded. Data were analysed using a Mann–Whitney U test and presented as median (minimum–maximum range), with significance set at p < 0.05.ResultsGroup M showed lower GCMPS-SF pain scores [15 (11–41) versus 31 (11–86); p = 0.023] and lower postoperative methadone requirements [0 (0–0.2) versus 0.25 (0–0.5) mg kg^–1; p = 0.029] than group C. There were three treatment failures in group C only. Food consumption and time to first urination did not differ between groups.Conclusions and clinical relevanceEpidural morphine reduced the requirement for postoperative analgesia in this study population.     

Outcome from status epilepticus after portosystemic shunt attenuation in 3 dogs treated with propofol and phenobarbital

Objective – To describe outcome of treatment with propofol and phenobarbital for status epilepticus (SE) after portosystemic shunt (PSS) attenuation. Case or Series Summary – Three dogs without preceding seizure activity, were diagnosed with a single extrahepatic PSS. Following standard preoperative medical therapy, an ameroid constrictor was placed surgically. Recovery was uneventful until spontaneous SE developed 46–96 hours after surgery. After unsuccessful seizure control with benzodiazepines, dogs were treated with a bolus of propofol followed by a propofol constant rate infusion. Phenobarbital was concurrently administered and supportive care was optimized. All dogs recovered uneventfully over the next 7–9 days. Over the following months phenobarbital was slowly tapered. All dogs have been free from antiepileptic drugs for several months, without recurrence of neurologic signs. New or Unique Information Provided – In this case series, we describe the treatment of 3 dogs with propofol and phenobarbital for refractory SE following attenuation of a single congenital PSS. After weaning of the propofol constant rate infusion, and tapering and discontinuation of phenobarbital over the following months, all dogs experienced a complete recovery. This study provides evidence that use of propofol in combination with phenobarbital may be efficacious for management of SE in dogs after PSS surgery.     

Plasma 14C-cholic acid clearance in healthy dogs and dogs with cholestasis or a congenital portosystemic shunt

The clearance profiles of intravenously injected tracer doses of radioactively labelled cholic acid were investigated in healthy dogs, dogs with a congenital portosystemic shunt and dogs with cholestasis. The rate constants and residual plasma activity were significantly different in the healthy and diseased dogs, but it was not possible to differentiate between the dogs with portosystemic shunting and cholestasis because the results were determined not only by factors involved in plasma bile acid clearance but also by the enterohepatic circulation.     

Perioperative outcomes after three different single extrahepatic portosystemic shunt attenuation techniques in dogs: partial ligation, complete ligation and ameroid constrictor placement

OBJECTIVE: To compare the perioperative outcomes of single extrahepatic portosystemic shunt occlusion by complete and partial silk ligation and ameroid constrictor placement in dogs. DESIGN: A retrospective analysis of 30 dogs with single congenital extrahepatic shunts. PROCEDURE: Records between 1990 and 2000 were reviewed. Patient age, breed, weight, presenting clinical signs, clinical pathology results, diagnostic imaging results, the surgery procedure performed, implant used, time taken, intra operative complications and perioperative complications were recorded. Mortality rates were calculated. RESULTS: Twenty dogs had a silk ligation procedure, 10 partially occluded and 10 completely. Ten dogs had an ameroid constrictor placement procedure. Ameroid constrictor surgery was significantly shorter in duration than silk ligation. Time for silk ligation was 91.8 +/- 35.2 minutes (median 90.0); time for ameroid constrictor placement was 71.5 +/- 12.0 (median 72.5, P = 0.049). A reduction in intraoperative complications was also noted in the ameroid constrictor surgery group. CONCLUSION: The ameroid constrictor offered a surgical occlusion procedure of single extrahepatic portosystemic shunts in dogs that was clinically as effective as silk ligation in the perioperative period, with a significantly shorter surgery time.     

Ultrasonographic assessment of hemodynamic changes in the portal vein during surgical attenuation of congenital extrahepatic portosystemic shunts in dogs

OBJECTIVE: To determine portal hemodynamic changes associated with surgical shunt ligation and establish ultrasonographic criteria for determining the optimal degree of shunt narrowing and predicting outcome. DESIGN: Case series. ANIMALS: 17 dogs, each with a single congenital extrahepatic portosystemic shunt. PROCEDURE: Pre- and postligation flow velocities and flow directions were determined by Doppler ultrasonography intraoperatively in the shunt and in the portal vein cranial and caudal to the shunt origin. Outcome was evaluated 1 month after surgery by measuring blood ammonia concentration and performing abdominal ultrasonography. RESULTS: Hepatofugal flow was detected in 9 of 17 dogs before shunt attenuation in the portal segment that was between the shunt origin and the entering point of the gastroduodenal vein. If hepatofugal flow became hepatopetal after shunt ligation, hyperammonemia resolved. Hepatofugal portal flow was caused by blood that flowed from the gastroduodenal vein toward the shunt. Shunt attenuation converted hepatofugal flow to hepatopetal in the shunt in 12 of 17 dogs. Chronic portal hypertension developed or perioperative death occurred when the portal congestion index caudal to the shunt origin increased by > 3.6 times. CONCLUSIONS AND CLINICAL RELEVANCE: After hepatopetal flow in the cranial portal vein and the shunt is established, further shunt narrowing is contraindicated. Increase of the portal congestion index caudal to the shunt > 3.5 times should be avoided. Poor outcome because of severe hypoplasia of the portal branches can be expected if the flow direction remains hepatofugal after shunt occlusion cranial to the shunt origin.     

Intraoperative contrast echocardiography to verify the surgical occlusion of a single extrahepatic portosystemic shunt in a dog

This report details a bubble echocardiographic study carried out during the surgical treatment of a congenital single extrahepatic portosystemic shunt (PSS) in a Labrador Retriever. After celiotomy, agitated saline was injected through a jejunal vein and microbubbles appeared rapidly in the right cardiac chambers. The test confirmed the presence of a PSS, helping the surgeon to identify the vessel concerned and to rule out a second shunt. Successively, portography confirmed what the exploratory celiotomy had revealed before with the aid of the bubble study: a single shunt was located between the portal vein and the right renal vein. It was completely ligated, as all the criteria for this solution were met. Intraoperative contrast echocardiography (ICE) was easy to perform, helpful and undemanding. It is proposed here as an intraoperative ancillary test to diagnose all PSS and to confirm successful treatment when complete shunt closure is possible.     

Effects of single intravenously administered doses of dexamethasone on response to the adrenocorticotropic hormone stimulation test in dogs

The effects of single IV administered doses of dexamethasone on response to the adrenocorticotropic hormone (ACTH) stimulation test (baseline plasma ACTH, pre-ACTH cortisol, and post-ACTH cortisol concentrations) performed 1, 2, and 3 days (experiment 1) or 3, 7, 10, and 14 days (experiment 2) after dexamethasone treatment were evaluated in healthy Beagles. In experiment 1, ACTH stimulation tests were carried out after administration of 0, 0.01, 0.1, 1, and 5 mg of dexamethasone/kg of body weight. Dosages greater than or equal to 0.1 mg of dexamethasone/kg decreased pre-ACTH plasma cortisol concentration on subsequent days, whereas dosages greater than or equal to 1 mg/kg also decreased plasma ACTH concentration. Treatment with 1 or 5 mg of dexamethasone/kg suppressed (P less than 0.05) post-ACTH plasma cortisol concentration (on day 3 after 1 mg of dexamethasone/kg; on days 1, 2, and 3 after 5 mg of dexamethasone/kg). In experiment 2, IV administration of 1 mg of dexamethasone/kg was associated only with low (P less than 0.05) post-ACTH plasma cortisol concentration in dogs on day 3. In experiment 2, pre-ACTH plasma cortisol and ACTH concentrations in dogs on days 3, 7, 10, and 14 and post-ACTH plasma cortisol concentration on days 7, 10, and 14 were not affected by dexamethasone administration. The results suggest that, in dogs, a single IV administered dosage of greater than or equal to 0.1 mg of dexamethasone/kg can alter the results of the ACTH stimulation test for at least 3 days. The suppressive effect of dexamethasone is dose dependent and is not apparent 7 days after treatment with 1 mg of dexamethasone/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Failure to induce mucosal disease in cattle persistently infected with bovine viral diarrhea virus by treatment with adrenocorticotropic hormone

Recent research has shown that cattle that develop mucosal disease (MD) often, if not always, have been persistently infected with bovine viral diarrhea virus (BVDV) since birth. The purpose of the present study was to determine whether MD could be induced by immunosuppression of persistently BVDV-infected cattle. For that purpose, adrenocorticotropic hormone (ACTH) was injected intramuscularly, twice daily for 5 consecutive days in 4 persistently BVDV-infected cattle and in 3 control cattle. Before the ACTH treatment, the numbers of leukocytes, neutrophils and mononuclear cells (MNC) per litre of blood in BVDV-infected cattle were in the same range as in the controls. Similarly, the proportions of B cells, T cells, monocytes and Fcγ⁺ cells (cells with receptor for the Fc part of IgG) were the same in the 2 groups of animals. On the other hand, the proliferative response to mitogen stimulation of MNC obtained from the control animals was twice as high as the corresponding value of the persistently BVDV-infected cattle.In all animals, ACTH treatment caused increased Cortisol concentrations, leukocytosis, neutrophilia and decreased mitogen-induced lymphocyte stimulation. However, the MNC count and the proportions of B cells, T cells, Fcγ⁺ cells and monocytes remained unaltered. In spite of the immunosuppression, indicated by the decrease in mitogen-induced lymphocyte stimulation. ACTH treatment did not provoke any clinical signs of MD in the persistently BVDV-infected cattle.