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Indeed! You would have to rely on all of these parameters. You could run a BAST, but I would not rely on that alone. It would have to be part of the bigger picture.
Scott 🙂
Hello again.
Hepatotoxicosis from phenobarbital appears to be dependent on cumulative dose. Signs typically develop after a year or more of phenobarbital treatment, and the duration of administration is associated with the degree of histologic injury in epileptic dogs. Presentation can range from subclinical increases in serum bile acids to fulminant liver failure. Patients are likley to improve when the phenobarbital is withdrawn.
For dogs with hepatotoxicosis during chronic phenobarbital treatment, phenobarbital should be discontinued, or the dosage minimized, by adding another anticonvulsant. For example, potassium bromide (KBr) can be substituted at a maintenance dosage of 40-60 mg/kg PO q 24 h, and phenobarbital can then be discontinued with a rapid taper over 1-3 weeks. Clinically significant hepatotoxicosis can be preempted in most dogs by serial monitoring of serum bile acids, phenobarbital concentrations, and a liver panel, ideally every 6 months. Serum phenobarbital concentrations >40 mcg/mL should be avoided, as this can be a risk factor for hepatotoxicosis. In addition, the presence of hyperbilirubinemia, new hypoalbuminemia, or discordant increases in serum ALT > AP is clinically significant. Newly noted sedation on a stable dosage of phenobarbital might also indicate impaired hepatic clearance of the drug, and is an indication for bile acids testing.
Overall, it matters less about the AP, treatment decisions would be made on the parameters above.
Hope that helps.
Scott 🙂
Hello.
Thanks for the great question. About 1-2% of hyperthyroid cats that are given the antithyroid drug methimazole develop clinical evidence of hepatopathy with jaundice, typically in the first month of treatment. These changes are distinct from “innocent” increases in ALT and ALP seen with untreated hyperthyroidism. Hepatopathies can present with a predominantly hepatocellular or cholestatic pattern, with or without hyperbilirubinemia. These reactions usually are reversible with drug discontinuation, but can be fatal if not detected promptly. The increases in ALT and ALP tend to be higher with the methoimazole toxicity. Often, if hyperthyroidism is well treated, the innocent pre-treatment increases will normalise. The drug reaction will often occur with jaundice which would also help to distinguish. I would stop treatment if you suspected an adverse reaction.
Cats treated with methimazole should be screened for increases in ALT and AP if clinical signs of lethargy or anorexia are noted. If cats develop adverse clinical signs, idiosyncratic toxicosis (hepatopathy, blood dyscrasias, or facial excoriation) should be ruled out with a physical exam, CBC, and biochemical panel. The presence of these idiosyncratic adverse events warrants discontinuation of methimazole, given the risk of progression to more severe manifestations.49 The transdermal route does not appear to be beneficial in preventing idiosyncratic methimazole toxicosis, including hepatotoxicosis. Given the role of glutathione depletion in methimazole hepatotoxicosis in experimental models, the efficacy of glutathione precursors needs to be evaluated in the management of this adverse drug reaction.
You would have to find an alternative treatment in this situation. These severe adverse reactions seen with methimazole therapy are not reported with carbimazole, but they can still happen. It makes little sense that adverse reaction profiles would be very different between the two drugs because carbimazole is metabolized to methimazole in order to exert its therapeutic effect.
Hope that helps.
Scott 🙂
Hello.
Thank you so much for the question. I generally will monitor while the patient is on steroids. There is little need to monitor specifically for a steroid hepatoapthy when the steroids have been discontinued or when the patient is on a much lower tapered dose. The intensity of monitoring will also depend on the condition that the steroids are treating. Overall, while on higher doses of steroids I would be running biochemistry (to include at least ALT) as a minimum every 4-6 weeks. Normally all changes (blood and liver) are reversible.
There a a few reasons I think that is important. Steroid hepatopathy traditionally has been considered benign in dogs. However, the reported association between glycogen-like hepatopathy and hepatic remodeling and carcinoma in Scottish Terrier dogs, and between hyperadrenocorticism and gallbladder mucocele, suggests that all canine vacuolar hepatopathies should be taken more seriously, particularly when they are chronic and severe. The most effective treatment for steroid hepatopathy is to remove the source of exogenous or endogenous glucocorticoids. Where this is not possible, antioxidants are indicated. S-adenosylmethionine given to dogs with steroid-induced hepatopathy has increased total hepatic glutathione and had a beneficial effect on the oxidized : total glutathione ratio in hepatocytes, but had no effect on the histological appearance of vacuoles.
As you mention, PUPD will be part of the clinical signs anyways. Any sign of the patient becoming more systemically unwell (V+/D+, lethargy, anorexia) would warrent repeat blood work. In these cases liver function parameters would have to be evaluated. It would be unusual for a steroid hepatoapthy to progress to severe liver failure.
Hope that helps.
Scott 🙂
Hello again.
This is the reply from my specialist anaesthesia pal!
“Hi Scott. I’ve tried to get hold of the Dechra data as to where this dose came from, and evidence of efficacy to have obtained the licence for Pardale, but with no success. The UK vet advisors were keen to help (they don’t know either) but access was blocked by their central R&D team. I personally tend to dose at the lower doses you mention, although I know some anaesthetists are happy to go with the higher dose for the first few days then drop to 10mg/kg if staying on it longer term. Not sure any evidence behind this either though!”
Overall, I would stick to the 10-15mg/kg dose, but use of Pardale with the higher doses should also be fine.
Scott 🙂
Hello.
Hope you are well. This is not a drug I really use. I would normally use the 10-15 mg/kg dose.
I have contacted a specialist anaesthesia friend to get a bit more information for you about this higher dose.
Will get back to you ASAP!
Scott 🙂
I would not get through the day without Google!
Differentials for causes of an absolute polycythemia:
1. Primary (neoplasia, genetic).
2. Secondary
(a) Appropriate (cardiac (right-to-left shunting patent ductus arteriosus, persistent truncus arteriosus, ventricular septal defect, atrial septal defect, tetralogy of Fallot), respiratory (pulmonary parenchymal disease, pulmonary vascular amyloidosis), environmental (high altitude, severe obesity)).
(b) Inappropriate (renal disease (pyelonephritis, local hypoxia), neoplasia (renal lymphoma, renal fibrosarcoma, renal cell carcinoma, nasal fibrosarcoma, Schwannoma), metabolic (hyperadrenocortisism and hyperthyroidism), iatrogenic (exogenous erythropoietin therapy)).
Primary absolute polycythemia is a neoplastic myeloproliferative disorder of the erythroid stem cells. The neoplastic stem cells produce red blood cells independant of erythropoetin. Secondary polycythemia can be either appropriate or inappropriate. Appropriate secondary polycythemia is due to systemic hypoxia causing an appropriate compensatory response increasing erythropoetin production resulting in an increase in red blood cells which increases oxygen carrying capacity of the blood. Inappropriate secondary polycythemia is the increase of erythropoetin in the absence of hypoxic stimuli. The main causes of inappropriate polycythemia have been reported to be neoplastic in origin, such as renal sarcoma.
Differentiating between primary and secondary polycythemia is difficult. It is possible to measure erythropoetin concentrations at a specialised laboratory. However, the clinical evaluation of these results is limited as there can be an overlap between erythropoetin concentration in clinically normal and polycythaemic patients. As such erythropoetin measurement, where available, is recommended to be used as an aid in confirming a diagnosis of secondary polycythemia.
Scott 🙂
You are totally right!
I ran the bloods again and they were totally normal!
This sample most likely had a blood clot in it!
I am just pleased I did repeat the sample and did not go ahead with the transfusion!
Scott 🙂
Hey.
Bloods were all fine. I think this is most likely to be a ‘gravel sign’. The gravel sign is seen radiographically as multiple, variously sized mineral fragments in the stomach or intestine, which build up as a result of poor gastric motility and/or emptying, and indicate a chronic stasis of food. It can be present in cases of both partial and complete obstruction. Heavier particles tend to settle in front of a partial obstruction, as fluid and less dense particles move beyond the obstruction.
The puppy was later reported to have possibly have eaten some cat litter which might help explain it!
Scott 🙂
Hey Mike.
I am so sorry about the delay with this. You may also notice I seem slightly distracted mid conversaton here and look down to the right… that may be the moment one of my children were crawling out from under the desk!!! COVID recording has been tough! 🙂
Anyway, sorry for any confusion. Everything listed on this slide is a possible complication post surgery. On this slide the ‘neurological’ that I refer to is the post attenuation neurological syndrome:
Postoperative complications associated with PSS usually include neurologic abnormalities, acute portal hypertension, and persistent shunting (either through the original shunt or via the development of APSSs). Postoperative seizures not associated with HE or hypoglycemia have been reported in up to 12% of dogs. Preoperative phenobarbitone appeared to reduce the severity but not the incidence of neurologic sequelae following shunt surgery in one study. In another study, levetiracetam 20 mg/kg PO q 8 h for ≥24 h preoperatively significantly reduced the incidence of postoperative seizures in dogs with EHPSS. Postoperative seizures occur in dogs and cats, are independent of the type of attenuation performed, can occur days later, and do not appear to be caused by the original HE. All patients having undergone surgery for PSS should be monitored closely for neurologic sequelae. There is no agreed-upon algorithm for treating these signs; however, intensive management should be instituted immediately with anticonvulsant therapy and/or propofol boluses (1-3.5 mg/kg IV) followed by propofol IV constant rate infusions (CRIs) (0.1-0.2 mg/kg/min or higher).
Hope that helps.
Scott 🙂
Thanks so much for picking this discussion back up! 🙂
Initially the patient was placed in an oxygen chamber. Butorphanol 0.3mg/kg was administered, intramuscularly. After twenty minutes, the patient’s respiratory rate was still 50 breaths per minute and no change in respiratory effort was noted. The patient was removed from the oxygen chamber and flow-by oxygen therapy was administered. It was not possible to obtain an arterial blood sample. An intravenous catheter was placed into the right cephalic vein. A venous blood sample was obtained for a minimum database (PCV, total solids, glucose and blood urea nitrogen (BUN)), acid-base analysis, electrolytes and haematology. Manual PCV and total solids were 74g/l and 70g/l respectively. Both glucose and BUN were within the normal reference range. The patient was hyperkalaemic; 4.8mmol/L (2.9 – 4.2). Haematocrit was 72% (24-40) and cHgb was 24.4 g/dL (8.0-13.0). All other haematological and electrolyte results were within the normal reference range. Coagulation testing showed that partial prothrombin (PT) time was within the normal reference range, however activated partial thromboplastin time (aPPT) was mildly prolonged at 167.2s (94-125) (Table 2). A thoracic ‘point of care’ ultrasound examination was performed and was negative for free fluid. Subjectively the left atrium was dilated with an abnormal left atrial to aortic (LA:Ao) ratio, however further assessment of the heart was not possible due to the cat’s temperament. No free fluid was present on abdominal point of care ultrasound. SpO2 was 97% from pinna.
It was initially suspected that the patient’s haemoconcentration was due to severe dehydration. As such, a fluid therapy plan was implemented. A 15ml/kg intravenous fluid bolus of Hartmann’s solution (Vetivex 11; Dechra) was administered over 15 minutes, after which intravenous fluid therapy (IVFT) was continued at a rate of 4ml/kg/hr for eight hours . Seven hours post presentation the patients PCV was 67%, and IVFT was continued at a reduced rate of 2ml/kg/hr thereafter. After twenty-four hours of fluid therapy the patient’s PCV was 65%. The patient was quiet, alert and responsive; however, the breathing had become more laboured despite continued oxygen therapy, and her respiratory rate was consistently between 60-70 breaths per minute .
The PCV and haematocrit are elevated, indicating that the patient is polycythemic; PCV>55%. It is important to distinguish between a relative polycythemia and an absolute polycythemia. Relative polycythemia is the loss of plasma water without the loss of red blood cells. It is caused by fluid imbalances causing reduced plasma fluid volume, such as dehydration, reduce fluid intake, redistribution of vascular blood, cutaneous losses or splenic contraction (in the dog). Absolute polycythemia occurs when red blood cell number increases and is classed as either primary or secondary. Despite fluid therapy, although slightly improved, the patient’s PCV was still significantly increased and as such this case is termed an absolute polycythemia.
What would be the differentials for an absoute polycythemia in this patient? Or is that an unfair question for a saturday night?!?!?
Scott 🙂
Yes! I had all the question marks too!!!
So… there is definately something abnormal in the stomach. The DV really allows us to see that it is definatley still in there. So… I did decide to scope this dog. There was lots of thick mucus in stomach with likley food material in it. Definately nothing obstructive and nothing I could remove with the scope.
I took a radiograph post endoscopy and the same opacity was there… what might be the other reason for this radiographic abnormaity?
Scott 🙂
Thanks for the update!
I do think some dogs just do this after castrayion, it would be good to hear others experience.
Do you think you will do further investigations? If not, it may be good to consider tranexamic acid before future surgery?
Scott 🙂
My relpy…
“Hope the wee guy is doing better.
This could definitely be one of this situations where this could be something or nothing. I have definitely seen dogs that have bleeding and bruising like this post castration and there is no real explanation for this.
In order to fully assess primary coagulation I would make sure to run a platelet count (manual) and consider a BMBT. A BMBT would be an easy way to asses for a thrombocytopathia. Can be tricky though in a conscious dog!
If PT and aPTT are normal then you could also consider D-dimers and fibrinogen.
The way to really assess coagulation in the best way would be to do TEG! That may give you the ultimate peace of mind!”
What do you all think?
Scott x
Yes.
I did say that. I just watched it back. Sorry the quality was not up to standard.
Let me know if you have any other questins.
Scott 🙂
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