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Canine Congenital Portosystemic Shunts Medical vs Surgical Management Cynthia RL Webster, DVM, DACVIM Specialty Rounds 7/18/12.

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Presentation on theme: "Canine Congenital Portosystemic Shunts Medical vs Surgical Management Cynthia RL Webster, DVM, DACVIM Specialty Rounds 7/18/12."— Presentation transcript:

1 Canine Congenital Portosystemic Shunts Medical vs Surgical Management Cynthia RL Webster, DVM, DACVIM Specialty Rounds 7/18/12

2 CPSS: Treatment Options Medical management Attenuation of vessel  Manage complications  Hepatic encephalopathy  Diet  Antibiotics  Lactulose  Urolithiasis  Diet  Surgery  Hepatic atrophy  Surgical attenuation  Laparotomy  Ligation  Ameroid constrictor  Cellophane banding  Laparoscopy  Interventional radiology

3 Surgery for everyone!! Pros Cons  Cure is possible  Eliminates need for lifetime daily administration of medication and feeding a special diet  Liver sizes returns to normal  Expensive  Morbidity  Mortality  Hepatic histopathology does not normalize  May not work  Develop acquired shunts

4 Complications of Surgical Attenuation MethodShort Term Mortality(%) Morbidity (%) Long Term (%) PL N=225 11.7 1232 CL N=108 7.1 8.69.5 AC N =39 6.9 7.1 13.5 10 7.7 6 CB N=100 5.5 9.4 12.6 ? 13 0 N=32 N=16 8

5 Outcome assessment Short termLong term  Survival  Complications  Portal hypertension  PNLS  Coagulopathy  Hypoglycemia  Quality of life  Clinically normal  Survival  Ultrasound  Flow through shunting vessel  Scintigraphy  Shunt fraction  Biochemical cure  TSBA  Ammonia tolerance

6 Short Term Complications: Portal Hypertension  Ligation2-18%  Cellophane banding0-2%  Ameroid 3.5-14%  Usually not life threatening  How many go on to develop PH after gradual occlusion?  End up with MAPSS  May be better clinically than with single shunt

7 Short Term Complications: Post ligation neurologic syndrome  Definition:  SZ: Serious potentially fatal complications  Any neurologic signs: tremors, blindness, ataxia  Incidence: 2-25%  Not due to hypoglycemia  Not due to hepatic encephalopathy  What is it due to?  Associated with rapid resolution of circulating toxemia as it can happen with IR and even with medical management

8 Tisdall PLTisdall PL et al, Neurological dysfunction in dogs following attenuation of congenital extrahepatic portosystemicshunts. J Small Anim Pract. 2000;41(12):539-46 Eleven of 89 dogs (12 per cent) developed neurological signs within six days of surgical attenuation of a congenital extrahepatic portosystemic shunt. Neurological signs were not associated with hepatic encephalopathy or hypoglycaemia. Signs varied in severity from non-progressive ataxia (threedogs) to generalised motor seizures (four dogs), progressing to status epilepticus (three dogs). In a further four cases, ataxia and disorientation were treated vigorously with anticonvulsant medication, presumably preventing the development of seizures. Two dogs that developed status epilepticus died or were eventually euthanased. All other animals survived, although some had persistent neurological deficits. Postligation neurological complications were not prevented by gradual shunt attenuation. Prophylactic treatment with phenobarbitone (5 to 10 mg/kg preoperatively, followed by 3 to 5 mg/kg every 12 hours for three weeks) did not significantly reduce the incidence of neurological sequelae (2/31 [6 per cent] dogs with phenobarbitone vs 9/58 [16 per cent] without phenobarbitone; P = 0.2). However, no animal receiving phenobarbitone experienced generalised motor seizures or status epilepticus. In conclusion, these observations suggest that postligation neurological syndrome comprises a spectrum of neurological signs of variable severity. Perioperative treatment with phenobarbitone may not reduce the risk of neurological sequelae, but may reduce their severity

9 Fryer KJ et. al. Incidence of postoperative seizures with and without levetiracetam pretreatment in dogs undergoing portosystemic shunt attenuation. J Vet Intern Med. 2011 25(6):1379-84. In dogs with congenital portosystemic shunts (CPS), postligation seizures can be challenging to treat and often result in mortality. Levetiracetam (LEV) is a novel anticonvulsive drug that is commonly used in humans with seizure disorders who have hepatic comorbidity. To compare the incidence of postoperative seizures in dogs that underwent surgical attenuation of an extrahepatic CPS and preoperatively received either LEV or no anticonvulsant medication.A total of 126 dogs undergoing attenuation of an extrahepatic CPS that preoperatively received either LEV or no anticonvulsant medication. Retrospective case review. Information obtained included signalment, duration of clinical signs, presence of neurologic abnormalities before surgery, preoperative bile acid and ammonia concentrations, diagnostic imaging modality, duration of hospitalization, postoperative complications including seizures, and discharge status. Bayesian Poisson regression was used to estimate the risk of seizures in LEV-treated dogs when compared with untreated dogs. Levetiracetam was administered to 33% (42/126) of dogs. No dog treated with LEV experienced postoperative seizures, whereas 5% (4/84) of dogs not treated with LEV experienced postoperative seizures. The relative risk of seizures was significantly (P <.0002) < 1 for the LEV-treated dogs, indicating LEV protection against development of postoperative seizures. No dog that experienced post operative seizures survived to discharge from the hospital. Levetiracetam administered at 20 mg/kg p.o. q8h for a minimum of 24 hours before surgery significantly decreased the risk of postoperative seizures and death in dogs undergoing surgical attenuation of extrahepatic CPS with ameroid ring constrictor.

10 Short term complications: Coagulopathy  Coagulopathy  Hemorrhage  Thrombosis  PVT (usually associated with additional predisposing factor)  Reported abnormalities  Prolonged PT and aPTT  Decreased AT  Decreased PC  Increased FVIII and wVF  Mild thrombocytopenia with normal platelet function

11 CoagYN Hyper729 Normal3912 101121 P=.02997 Avg: 7813 +/- 1615 Median: 8364 (3940 -10200) Normal: 6156 +/-1144 TEG Parameters in Dogs with CPSS Normal CPSS Signs of HE

12 Short term complications Hypoglycemia  Poor glycogen stores  Hepatic atrophy  Not due to hyperinsulinemia  Not associated with relative adrenal insufficiency

13 Improve surgical outacome Who is not going to do well at surgery? Not associated with outcome  Age at which surgery is done  Increases in liver enzymes  Shunt fraction  Pre and post ligation portal pressure  Changes on hepatic histopathology (?)

14  Degree of attenuation: PL is worse  Intrahepatic vs extrahepatic: IH is worse  Decreased albumin  Seizures post-operatively  HE prior to surgery  Leukocytosis  Intraoperative portovenography  Persistent hepatofugal flow post-operatively  Changes on hepatic histopathology (?)  Degenerative centrolobular lesions Maybe associated with outcome Who is not going to do well at surgery?

15 Laparoscopy  Miller and Fowler 2006  2 dogs cellophane band with EH shunts in Labrador and a Yorkie.  Did well

16 Interventional Radiology (IR)  Transvenous coil embolization  Most IH (Largest case study only reported in abstract x 2 and proceedings x, about100 dogs)  Median survival: 6 yrs (0-9.3)  Outcome: 74% good to excellent  18% required more than one coiling  Complications:  PH (1-2%)  Bleeding  GI hemorrhage (initially 20%)  Many dogs have evidence of inflammatory bowel disease  Treat with omeprazole  Neurologic (6%)

17 Medical Management Watson PJ, Herrtage ME. Medical management of congenital portosystemic shunts in 27 dogs--a retrospective study. J Small Anim Pract. 1998 ;39(2):62-8. Case records of 27 dogs with medically managed congenital portosystemic shunts were reviewed. Fourteen were followed up by telephone questionnaires to the owners. Age, breed, sex, clinical signs and blood results were similar to previous studies. Weight and quality of life were stable or improved on treatment in all cases. Total serum protein concentration and alanine aminotransferase and alkaline phosphatase activities fell significantly during treatment. Fourteen dogs were euthanased, four were lost to follow-up and nine remained alive. Mean survival time for the dogs euthanased was 9.9 months. Mean follow-up period for the dogs still alive was 56.9 months and all had survived more than 36 months from diagnosis. Surviving dogs with intrahepatic shunts had a significantly shorter follow-up period than dogs with extrahepatic shunts. Two prognostic indicators were identified, age at initial signs and blood urea concentration on presentation, both correlating with survival time. It was demonstrated that a significant proportion of dogs with portosystemic shunts managed medically have a good prognosis,. Older at diagnosis, higher the BUN the longer the dogs were likely to survive

18 Medical vs Surgical Management Greenhalgh SN et. al. Comparison of survival after surgical or medical treatment in dogs with a congenital portosystemic shunt. J Am Vet Med Assoc. 2010 ;236(11):1215-20 OBJECTION : To compare survival of dogs with a congenital portosystemic shunt (CPSS) that received medical or surgical treatment. DESIGN: Prospective cohort study. BUT not randomized ANIMALS: 126 client-owned dogs with a single CPSS. PROCEDURES: Dogs were examined at 1 of 3 referral clinics, and a single CPSS was diagnosed in each. Dogs received medical or surgical treatment without regard to signalment, clinical signs, or results of hematologic or biochemical analysis. Survival data were analyzed via a Cox regression model. RESULTS: During a median follow-up period of 579 days, 18 of 126 dogs died as a result of CPSS. Dogs treated via surgical intervention survived significantly longer than did those treated medically. Hazard ratio for medical versus surgical treatment of CPSS (for the treatment-only model) was 2.9 (95% confidence interval, 1.1 to 7.2). Age at CPSS diagnosis did not affect survival. CONCLUSIONS AND CLINICAL RELEVANCE: Both medical and surgical treatment can be used to achieve long-term survival of dogs with CPSS, although results of statistical analysis supported the widely held belief that surgery is preferable to medical treatment. However, the study population consisted of dogs at referral clinics, which suggested that efficacy of medical treatment may have been underestimated. Although surgical intervention was associated with a better chance of long-term survival, medical management provided an acceptable first-line option. Age at examination did not affect survival, which implied that early surgical intervention was not essential. Dogs with CPSS that do not achieve acceptable resolution with medical treatment can subsequently be treated surgically

19 Medical vs Surgical Management S.A. Center et. al. Long-term survival of dogs (N = 597) with congenital or acquired portosystemic shunting: 1980–2010. ACVIM 2012 Surgical attenuation is preferred treatment for canine congenital portosystemic vascular anomalies (PSVA). However, success of long-term medical management of large canine PSVA cohorts and dogs with anicteric acquired portosystemic shunts (APSS) is undetermined. A retrospective survival study of dogs with PSVA (extrahepatic [EPSVA, n = 378], intrahepatic [IPSVA, n = 105]) and anicteric APSS (n = 114) over 31 contiguous years at Cornell University is described. Follow- up (91.5% cases) was derived from medical records and contact with managing veterinarians and clients. Medical management consisted of dietary protein restriction/modification, ± lactulose, ± metronidazole. Surgical PSVA attenuation was by suture ligation (n = 225/239) to tolerance. Age at diagnosis, survival of EPSVA and IPSVA treated surgically (n = 189 and 50, respectively) and medically (n = 166 and 46, respectively), and APSS survival were compared using Wilcoxon rank sum test, Kaplan-Meier survival curves, and two sample survival tests (Gehran-Wilcoxon and Log Rank Tests), respectively with alpha ≤ 0.05. Dogs dying without treatment were censored. Survivals (years) at 50th (range: 75th–25th) percentiles are shown. Median age (years) at diagnosis was significantly younger for PSVA (1 [0.1–12]) vs APSS (4 [0.12–12]), and IPSVA (0.5 [0.1–5]) vs EPSVA (1.5 [0.12–12]); P ≤ 0.00001. EPSVA survival (all dogs: n = 334, 10 [6.0–13]; Yorkshire Terriers: n = 91; 12 [6–13]) was significantly longer than IPSVA: n = 104, 4.5 (1.2–9); all P < 0.00001. There was no survival difference between surgically- or medically- treated EPSVA (all dogs; Yorkshire Terriers [n = 41 and n = 43, respectively]), and surgically- or medically-treated IPSVA. Of surgically treated dogs, 63% EPSVA and 58% IPSVA also received medical treatment. APSS survival (9.0 [4.6–11]) was significantly shorter than medically-treated EPSVA (all dogs: 10 [6–13]; Yorkshire Terriers:12.0 [6.0–13]), all P < 0.04

20 IHEHYorkie’s Surgery * 8.0 (43)10.5 (184)11.8 (41) Medical $ 5.5 (40)10.5(165)11.8 (43) Median Survival in Years * = suture ligation to tolerance $ = lactulose +/- metronidazole and dietary protein titration Numbers in parenthesis = number of dogs Center SA et. al. Long-term survival of dogs (n = 597) with congenital or acquired portosystemic shunting: 1980–2010. ACVIM 2012

21 Medical Management  Control HE  Lactulose  Metronidazole  Modulation of dietary protein  ID Precipitating factors  GI bleeding  High protein meal  Alkalosis  Sedative/analgesics/anesthetics  Catabolic conditions  Azotemia  Constipation

22 Tivers MS et al. Treatment of extrahepatic congenital portosystemic shunts in dogs - what is the evidence base? J Small Anim Pract. 2012;53(1):3-11. J Small Anim Pract.  A variety of surgical treatments and medical therapies are recommended for dogs with extrahepatic congenital portosystemic shunts (CPSS). The objective of this review was to assess the evidence base for the management of extrahepatic CPSS in dogs. An online bibliographic search was performed in November 2010 to identify articles relating to the question "Which of the treatment options for extrahepatic CPSS in dogs offers the best short- and long-term outcomes?" Articles were assigned a level of evidence based on a modified grading system. Thirty-eight articles were included in the review. Thirty-six articles were classified as grade 4 and two as grade 5. The timings and methods of assessment of short- and long-term outcomes varied widely between studies. One prospective study (grade 4a) showed that surgically treated dogs survived significantly longer than medically treated dogs. Four retrospective studies (grade 4b) compared the outcome of two surgical techniques but there were no statistically significant differences between treatment groups in terms of complications or outcome. The review found that the evidence base for the treatment of extrahepatic CPSS is weak. There is a lack of evidence of short- and long-term outcomes to recommend one treatment over another

23 What about cats? SpeciesShort Term Mortality Morbidity Good long term outcome Dog 8% 11%85% Cat 7.6 % 37%46% Increased incidence of neurological complications Portal vein thrombus Limited number of studies Ligation: 70 cats AC:34 cats CB:14 cats No studies looking at success of medical management

24 The future  Additional (hopefully prospective randomized) studies on outcome  Adequate follow-up (these are young dogs)  Standardize outcome  Short term: Morrtality and complications  Long term: QOL, recurrence of clinical signs, survival  Enhance growth of hepatic portal vasculature  Mesenchymal stem cells  Hepatocyte growth factor  Determine etiology of PLNS

25 Lipscomb VJLipscomb VJ, Jones HJ, Brockman DJ. Complications and long-term outcomes of the ligation of congenital portosystemic shunts in 49 cats. Vet Rec. 2007;160(14):465- 70Jones HJBrockman DJ Vet Rec. Only two of 49 cats undergoing surgical ligation of congenital extra- and intrahepatic portosystemic shunts died perioperatively, a mortality rate comparable with the mortality rates of dogs undergoing surgical attenuation of congenital portosystemic shunts and cats in which the shunts are attenuated with an ameroid ring constrictor. Thirty (83 per cent) of the 36 cats for which long- term information was available were still alive at a median follow-up period of 47 months (range six to 105 months); the outcome was excellent (no clinical signs) in 20 of them (median follow-up 37 months, range six to 105 months) and good (minimal clinical signs) in seven (median follow-up 39 months, range 10 to 73 months) and none of these 27 cats was on any long-term medication or special diet. The only major cause of morbidity was the development of neurological signs in 18 (37 per cent) of the cats. These included seizures and a wide variety of other neurological signs, and their development and persistence was not affected by the presence of preoperative seizures, the type of shunt, the degree of shunt attenuation or the age of the cat. The serum concentrations of ammonia and preprandial bile acids were normal or significantly below normal in the cats with neurological signs. Liver histopathology was similar in the cats with and without neurological signs. Ten (56 per cent) of the 18 cats that developed neurological signs recovered normal neurological function long term

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