Feline Hypertension

*** If you find these podcasts useful and interesting, PLEASE click on the iTunes icon below, then the "View in iTunes" blue link, and then rate and/or review the podcast. That will be really great and much appreciated. Thank you! ***
 

Episode based on:

ISFM Consensus Guidelines on the Diagnosis and Management of Hypertension in Cats. J Fel Med Surg 2017. 19:288–303.

1. Evidence base:

Guidelines based on comprehensive review of currently available literature; where clinical studies and scientific data were not available the Guidelines represent consensus opinion of the Panel.
Many areas where more data is required which may either confirm recommendations in these Guidelines or cause some to be modified.

2. Secondary versus primary hypertension:

Feline hypertension more commonly diagnosed in association with another disorder, i.e. secondary hypertension more common than primary (idiopathic) hypertension.
Most common associated disorder is chronic kidney disease followed by hyperthyroidism; there are others but they are much less common.
Unlike in humans, prevalence of hypertension in cats with diabetes mellitus is typically low, but often confounded by concomitant conditions such as CKD.

In secondary hypertension “the relationship between the hypertension and the underlying disease may not always be understood.”
Concurrent underlying disease must be managed as well as possible – which will help management of hypertension as well.

3. Target organ damage:

Can be severe and potentially irreversible
Main target organs: eyes, heart and vasculature, brain, kidneys
Problem(s) relating to TOD may be reason for presentation; especially vision impairment due to hypertensive ocular changes.

“Hypertensive ocular changes have been reported in approximately 50% of hypertensive cats…However, the high prevalence of reported ocular lesions may reflect the relatively late diagnosis of hypertension in many studies.”

“The retina and choroid have separate blood supplies and both can suffer hypertensive damage…with an array of fundic lesions visible on ophthalmoscopy”.

“Many cats with severe hypertensive ocular damage present with blindness and bilateral mydriasis resulting from complete retinal detachments and/or intraocular haemorrhage; the changes are often irreversible…Lesions that are not associated with an impaired menace response or pupillary light deficits...are much more amenable to anti-hypertensive treatment…highlighting the importance of early diagnosis and management. Detection of early hypertensive ocular lesions requires an ocular examination to be performed on all cats at risk of developing lesions.”

4. Monitoring and Underdiagnosis:

Early diagnosis followed by appropriate therapeutic management should help reduce hypertension-associated morbidity associated; however authors suggest monitoring is generally performed infrequently probably leading to underdiagnosis.
Encouraged to identify and monitor patients at risk of developing hypertension.

5. Which cats should we monitor blood pressure in?

Authors’ recommendations:

  • Any cat that has been diagnosed with a recognised risk factor for hypertension, such as chronic kidney disease or hyperthyroidism, should have their blood pressure measured at the time this diagnosis is made and then every 3-6 months thereafter.
  • Any cat that has an unexplained disease compatible with hypertensive target organ damage should also have their blood pressure measured immediately and then every 3-6 months thereafter.
  • Check blood pressure at least every 6–12 months in healthy cats aged eleven years or older.
  • Check blood pressure every 12 months in healthy cats aged 7-10 years.

Should we consider checking blood pressure every 12 months in healthy adult cats 3–6 years of age? “The main purpose of monitoring in this age group is to obtain baseline measurements for the individual cat. As few cats in this age category have hypertension, great care is needed in the interpretation of elevated BP measurements, especially in the absence of [target organ damage] or a clear underlying disease.”

5. Ensure BP is measured as accurately as possible with a reproducible technique:
   
Major take-home message alert!!!

“Indirect measurement of BP in cats can be readily performed, although care is needed with both the choice and use of the equipment to ensure meaningful and accurate results are obtained.”

Recommend using either Doppler sphygmomanometry or high-definition oscillometry; HDO is more accurate, reliable and consistent and easier to perform than traditional oscillometry.

Only systolic blood pressure measurements should be used for clinical assessment. Diastolic and mean arterial pressure readings are less accurate and should generally be ignored.

Use of standardised protocols imperative to improve accuracy and reproducibility of measurements.

Guidelines include extensive recommendations by the Panel covering:

  • Cat’s environment
  • Acclimatisation
  • Personnel
  • Restraint and positioning
  • Choice and position of cuff
  • Actual use of equipment
  • Taking and interpreting measurements

Consistency is essential.

“Blood pressure is labile and varies considerably within and between cats, depending in part on their level of arousal, activity or stress.”

Clinical assessment of systolic blood pressure is also affected by many external variables including:

  • Operator
  • Conditions
  • Environment
  • Equipment
  • Position of the cat
  • Size of the cuff
  • Site of measurement

6. ‘White coat hypertension’:

Temporary physiological increase in blood pressure due to excitement- or more likely anxiety-related sympathetic activation associated with veterinary visit.

7. Defining normal blood pressure:

“Establishing reference intervals for estimated [systolic blood pressure] in healthy cats using Doppler or oscillometric equipment is fundamental to the clinical diagnosis of hypertension, and also for determining therapeutic targets in affected cats.”

Provide results from three different studies but: “there is a wide discrepancy between different studies; this reflects, at least in part, the different populations examined, and differences in types of equipment and the way equipment was used. Thus, having a standardised technique is of paramount importance.”

Categories proposed by The International Renal Interest Society (IRIS):

  • Systolic blood pressure (SBP) <150mmHg = normotensive with minimal risk of target organ damage
  • SBP 150-159mmHg = borderline hypertensive with low risk of target organ damage
  • SBP 160-179mmHg = hypertensive with moderate risk of target organ damage
  • SBP >=180mmHg = severely hypertensive with high risk of target organ damage

Strict categorisation is problematic as blood pressure is labile and target organ damage is not only related to severity of hypertension but also duration and relative change.

8. Criteria for therapeutic intervention and appropriate therapeutic targets:

Criteria as per the Guidelines:

“While individual circumstances should always be carefully assessed, based on current knowledge the Panel suggests that antihypertensive therapy is generally justified if SBP is measured carefully and when:

a. Indirect SBP is ≥150 mmHg on a single occasion, and there is clear evidence of ocular or neurological TOD [target organ damage].

Note: if clinical signs do not respond appropriately to adequate antihypertensive therapy, the diagnosis should be reassessed and other potential causes of the signs investigated.

b. Indirect SBP is ≥160 mmHg on at least two separate occasions, and there is evidence of TOD including ocular, neurological, cardiac or kidney damage.

c. Indirect SBP is ≥170 mmHg on at least two separate occasions, and the clinician does not consider ‘white coat hypertension’ is likely to be the cause.

d. Indirect SBP is <150 mmHg, but there is clear evidence of active ocular TOD.

Note: cats should be monitored carefully. If there is any doubt about the diagnosis of hypertension, the need for long-term therapy should be reassessed by trial withdrawal of therapy once stable, and monitoring of BP and clinical signs.

Cats with SBP <150 mmHg and evidence of potential TOD should have their clinical signs and BP monitored carefully, and other possible causes of the signs investigated.”

Therapeutic target:

SBP <160mmHg generally associated with decreased risk of target organ damage and hopefully an improvement in patient’s health
Indeed may be more prudent to aim for <150mmg in long-term

9. What treatment should you use?

“Based on current data, amlodipine besylate is the treatment of choice to manage feline hypertension and is effective in the majority of cats, but the dose needed to successfully manage hypertension varies between individuals.”

Guidelines also cover approach to amlodipine dosing and routine BP monitoring.

“It is worth noting that the Guidelines were supported financially by an educational grant from Ceva to the ISFM and Ceva is a manufacturer of amlodipine; however I don’t think this invalidates the statement about amlodipine being the current treatment of choice.” (Shailen)

Amlodipine causes vasodilation (peripheral arterial dilator) via calcium channel blockade; good response seen in many hypertensive cats suggests increased vascular tone may be a common component of feline hypertension.

Adjuvant therapy required in some cats:

E.g. ACE inhibitors, angiotensin receptor blockers (ARBs), beta-blockers
Less effective; typically used in addition to not instead of amlodipine.

“The choice of adjunctive therapy to help manage hypertension may in part be dictated by any concurrent or underlying disease. For example, ACE inhibitors or ARBs may be indicated in CKD patients to help manage proteinuria”.

NB. Whenever hypertension is diagnosed, it is important to search for, and treat, underlying diseases as most cases of feline hypertension are secondary.

10. Emergency treatment of hypertension:

Hypertension generally chronic; acute presentations may be due to:

Acute onset of clinical signs due to target organ damage
Acute elevations of blood pressure (e.g. possible in acute kidney injury (AKI))

Aggressive intervention with oral +/- parenteral antihypertensive therapy may be tempting/seem rational but lack of definitive evidence to support positive risk-benefit assessment. 
Uncontrolled abrupt reduction in systolic blood pressure or development of hypotension can precipitate myocardial, cerebral or renal ischaemia and should be avoided.

[This podcast is closely aligned with the MedEdLIFE Research Collaborative's Quality Checklist for Podcasts.]
 

Tweet: Check out FREE audio podcasts from @VetEmCC http://ctt.ec/UqL8b+ Also available in iTunes/Stitcher. #veterinary #podcast

Hepatic Encephalopathy in Dogs and Cats

*** If you find these podcasts useful and interesting, PLEASE click on the iTunes icon below, then the "View in iTunes" blue link, and then rate and/or review the podcast. That will be really great and much appreciated. Thank you! ***

Listen to Stitcher
Subscribe on Android

Episode based on:

Lidbury JA, Cook AK, Steiner JM. Hepatic encephalopathy in dogs and cats. J Vet Emerg Crit Care 2016. 26 (4):471-487.

“The aims of this article are to comparatively review the pathogenesis, clinical presentation, diagnosis, and management of HE in dogs and cats. Gaps in the understanding of HE in dogs and cats and areas worthy of future study are also highlighted.”

What is Hepatic Encephalopathy?

“the spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction after exclusion of other known brain disease” from Hepatic encephalopathy – definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna 1998 (Hepatology, 2002).

Hepatic Encephalopathy – Classification

Three types in human medicine:

  • Type A: due to acute liver failure in the absence of pre-existing liver disease.
  • Type B: associated with portal systemic bypass without intrinsic hepatocellular disease; e.g. congenital portosystemic shunting in dogs and cats.
  • Type C: associated with cirrhosis and portal hypertension or acquired portal systemic shunting. Subcategorised according to duration and characteristics. Distinction made in people between ‘overt HE’ (signs of impaired mental status) and ‘covert HE’ (no altered mental status).

“can be applied to dogs and cats if the definition of type C HE is broadened to include cases associated with all intrinsic hepatocellular disease and portal hypertension or acquired portal systemic shunting.”

Covert HE currently not recognised in dogs and cats – likely exists but challenging to diagnose.

Schemes for grading severity exist in human medicine. No universally accepted guidelines to grading in dogs or cats. Some authors have adapted human grading schemes for use in dogs, e.g. Proot et al, 2009.

Hepatic Encephalopathy – Pathogenesis

Ammonia:

Evidence (more and better quality in people) for central role of ammonia dysmetabolism.
Gastrointestinal tract is main source of ammonia. Especially via breakdown of nitrogenous products (e.g. urea) by urease producing gastrointestinal microbial organisms; but also via conversion of glutamine to ammonia within intestinal mucosa.

Ammonia and the liver:

Liver is main site of ammonia detoxification (kidneys and skeletal muscle much less so): failure of hepatic detoxification leads to hyperammonaemia and higher cerebral exposure.

Main causes of inadequate hepatic detoxification:

1) Portosystemic shunting (PSS):

Most common reason in dogs and cats
Ammonia-rich splanchnic blood from the gastrointestinal tract bypasses hepatic uptake and flows directly into systemic circulation.
Two types of portosystemic shunt, extrahepatic and intrahepatic
Congenital vascular anomalies or acquired collateral blood vessels secondary to prehepatic or hepatic portal hypertension

[From http://communityvet.net/2010/04/when-protein-turns-toxic-jesse-story/pss/]

[From http://communityvet.net/2010/04/when-protein-turns-toxic-jesse-story/pss/]

2) Intrinsic liver dysfunction despite receiving ammonia-rich blood:

Due to acute liver failure or potentially chronic cirrhotic changes

Ammonia and the brain:

Brain is involved and active in ammonia handling
Ammonia passes freely across the blood brain barrier (BBB) in healthy individuals
Ammonia and pathogenesis of hepatic encephalopathy:

  • One of the most appealing theories is ammonia causes astrocyte swelling
  • Other potential mechanisms too
  • May also contribute to neurological dysfunction by increasing BBB permeability

“Dogs and cats with HE are often hyperammonemic, and successful treatment of HE is usually associated with a reduction in serum ammonia concentrations. However, patients may have HE despite a blood ammonia concentration within the reference interval suggesting that other mechanisms also play a role in the pathogenesis of HE.” (authors cite Rothuizen, van den Ingh, 1982).

Other pathogenic mechanisms of HE:

Infection and inflammation may play a role:

Clinical evidence in people
Non-infectious or infection systemic inflammatory response syndrome (SIRS) is common in people with both acute liver failure and cirrhosis
Inflammatory mediators may trigger HE by exacerbating cerebral effects of ammonia

Systemic inflammation also a potential phenomenon in dogs and cats with acute liver failure…“However, the relationship between inflammation and canine HE needs to be better defined. To the authors’ knowledge, this relationship has not been studied at all in cats.”

Others:

Neurosteroids found in high concentrations in the brain
Oxidative stress
Manganese
Amino acid balance

Hepatic Encephalopathy – Precipitating factors

People:

At least one trigger identified in 88 to 90% of those affected
Individuals with one or more triggers have a worse prognosis than those without
Most commonly reported include: gastrointestinal bleeding, constipation, diarrhoea, infection, hypokalaemia, hyponatraemia, and excess dietary protein.

Number of same factors can potentially precipitate HE in dogs and cats; some have been described in the veterinary literature. “However, the evidence base to support the role of many of these factors in veterinary species is weak or nonexistent.” Further investigation of the factors that may predispose dogs and cats to HE is needed.

Hepatic Encephalopathy – Clinical presentation

Signalment reflects most common causes of HE in dogs and cats, namely congenital or acquired portosystemic shunts.

Canine breeds most likely to be have congenital PSS (in descending order): Havanese, Yorkshire Terrier, Maltese, Dandy Dinmont Terrier, Pug, Miniature Schnauzer, Standard Schnauzer, and Shi Tzu. (Tobias, Rohrbach, 2003)

No studies evaluating which breeds are most likely to develop acquired shunting. Probably most likely in breeds predisposed to chronic hepatitis. Wide age range but typically older than dogs presenting for congenital PSS.

Congenital PSS reported in several cat breeds; unclear which – if any – are predisposed.
The authors say that although congenital shunts have been reported in a number of cat breeds, it is not clear which if any cat breeds are predisposed to HE and large-scale epidemiological studies will be needed to ascertain this.

Clinical signs:

Initially often subtle and episodic; can progress in intensity and frequency
May be exacerbated by eating
In one study (Lidbury et al, 2012)):

  • Most common historical findings: obtundation, altered behaviour, head pressing, ataxia, apparent seizures, vomiting, lethargy, ptyalism, apparent blindness, and shaking.
  • Most common neurological findings: obtundation, ataxia, weakness, conscious proprioceptive deficits, seizures, circling, cranial nerve deficits, stupor, and tremor.

Signs of HE in cats reportedly broadly similar to those in dogs. 

Hepatic Encephalopathy – Diagnosis

In veterinary medicine, based on:

  • Presence of consistent clinical signs
  • Exclusion of other causes of encephalopathy
  • Laboratory findings
  • Imaging studies, and
  • Response to treatment

Currently no way to evaluate dogs and cats that have HE but without impaired mental status.

Measuring blood ammonia concentration:

May or may not be elevated in dogs with HE

“In individual dogs, fasting ammonia concentrations poorly predict the severity of HE.” (Rothuizen, van den Ingh, 1982)

When accessible, seems to be performed routinely or at least commonly in veterinary patients suspected of having HE; not the case in human medicine.

Appropriate sample handling is critical:

  • Ammonium ions are extremely labile in plasma and ammonia may be released by red blood cells ex vivo.
  • Samples should be collected in a lithium heparin or EDTA tube, placed immediately on ice, and the plasma separated from the red blood cells as soon as possible.
  • Plasma must be kept cooled and should be analysed within 30 minutes of collection.

In-house and point of care analysers available: Reliability? Validation in dogs and cats?

“Measurement of pre- and postprandial serum bile acid concentrations is a useful test for diagnosing hepatobiliary disease, including portosystemic shunting, in dogs and cats. A definitive diagnosis of portosystemic-shunting requires diagnostic imaging or surgical exploration. Several imaging modalities are useful for this purpose, including angiography, abdominal ultrasonography, portal scintigraphy, computed tomography angiography, and MRI angiography. These imaging modalities, apart from portal scintigraphy, frequently allow the anatomic characterization of the shunt vessel(s)….For patients with acquired liver disease, a histological diagnosis is often necessary to define the underlying cause.”

Hepatic Encephalopathy – Treatment

Treating the underlying cause:

Various techniques for attenuation of congenital PSS
“Generally, signs related to HE improve after shunt attenuation…although incomplete closure can lead to persistent compromise. Dogs with a poorly developed portal vasculature may develop portal hypertension after shunt closure. This triggers the development of [acquired collateral circulation] with possible recurrence of HE. Postoperative seizures can also occur, the pathogenesis of which is unknown.”

Post-attenuation seizures “can occur in dogs and cats that do not have HE or other metabolic causes of seizures….Typical histological changes of the cerebrum in animals undergoing necropsy include selective “ischemic” neuronal necrosis and other changes that are consistent with ischemia or hypoxia. Withdrawal of endogenous benzodiazepines [post-congenital shunt] attenuation has also been proposed as a potential mechanism.”

Attenuation of acquired shunts contraindicated; these shunts are a compensatory response to portal hypertension and closure results in an acute exacerbation of portal hypertension.

General supportive care and treatment of precipitating factors:

Standard practice around:

  • Maintenance of fluid and electrolyte balance
  • Routine care of the comatose or stuporous patient
  • Management of suspected intracranial hypertension
  • Antimicrobial therapy for confirmed or highly suspected infection
  • Gastroduodenal ulcer treatment and prophylaxis

Warm water enemas:

Advised in this review to be performed in severely affected dogs and cats with HE until signs improve (reference is a single author book chapter).
Help remove blood and faecal matter from colon; therefore decrease bacterial ammonia production.
Also indicated for constipated patients with HE of all severity grades.

Nutrition:

Typical recommendation is protein-restricted diet containing specific types of protein sources.
Cats reportedly have a higher dietary protein requirement than dogs.
Diets recommended for HE also tend to have other modifications including reduction in some substances and supplementation with others.

“Although several commercially available diets are marketed for dogs and cats with HE, the optimal diet formulation has not been established.”

Lactulose:

A non-absorbable disaccharide
Potential beneficial effects:

  • Trapping of ammonium ions within the colon leading to decreased absorption of ammonia into the portal circulation
  • Inhibition of ammonia production by colonic bacteria
  • Stimulation of incorporation of ammonia within bacterial proteins
  • Reduced intestinal transit times leading to decreased bacterial ammonia release
  • Increased faecal excretion of nitrogenous compounds

Placebo controlled studies in humans support efficacy for treating overt HE. While lactulose is “commonly used to treat HE in dogs and cats [both acutely and chronically]…there are no studies that have critically evaluated the efficacy of this drug.”

Can be given per rectum after a cleansing warm water enema in acutely compromised patients but “it has not been proven that this has any benefits over a plain warm water enema.”

Antimicrobial therapy:

Aim to reduce ammonia production by altering intestinal microbiome
Neomycin:

  • Poor gastrointestinal absorption
  • Use no longer recommended in people as inadequate evidence of efficacy and risk of serious renal injury and ototoxicity
  • No good quality information about its use for HE in dogs and cats.

Metronidazole and vancomycin have also been used to treat HE in people; may be better tolerated in people than neomycin but their efficacy has not been rigorously established. Clinical trials have not been reported describing the efficacy of metronidazole for HE in dogs and cats.

Rifaximin (semisynthetic derivative of rifampicin) is US Food and Drug Administration approved for maintaining remission of HE in people. “The pharmacokinetics of rifaximin has been reported for dogs and this drug has been reported to be well tolerated in this species…The lack of apparent adverse effects is a potential benefit compared to neomycin and metronidazole. However, the safety and efficacy of this drug in dogs and cats with HE have not been established. Current costs are also likely to be prohibitive.”

Intravenous ampicillin (or potentiated amoxicillin) may be used in dogs or cats that cannot receive oral medications
Use of oral ampicillin also been reported

Anticonvulsants:

“Anticonvulsant drugs should be administered to patients with HE if seizures occur and in patients that seizure after attenuation of a congenital portosystemic shunt. Additionally, they are sometimes given to patients prior to shunt attenuation in an attempt to reduce the occurrence of postoperative seizures.”

“The use of diazepam and midazolam to treat seizures due to HE is controversial and there are no clinical trials that have evaluated the efficacy of these drugs in this setting. As diazepam is hepatically metabolized its half-life may be prolonged in dogs and cats with HE. Therefore, the dose and frequency that is used should be reduced in order to avoid causing profound sedation…In people benzodiazepine administration is considered to be a precipitating factor for HE.”

Levetiracetam:

  • Rapidly acting anticonvulsant with few side effects identified so far
  • Can be given intravenously or orally to dogs and cats
  • Principal route of excretion is renal so suitable for patients with hepatic compromise.
  • Use in dogs undergoing congenital PSS attenuation may be well tolerated and may reduce occurrence of postoperative seizures (Fryer et al, 2011).

Phenobarbital and propofol may also be used if required in acute situations
Potassium bromide can be used as an adjunct to other anticonvulsant drugs in dogs; of little use in emergency scenario due to very long half-life and delayed onset of action.

Other potential treatment options in people:

  • Flumazenil (intravenous benzodiazepine receptor antagonist): role of endogenous benzodiazepines in the pathogenesis of HE is controversial; only consensus is that flumazenil is useful when treating human patients with HE who have taken benzodiazepines.
  • L-ornithine-L-aspartate (or LOLA): thought to increase the rate of ammonia detoxification; early positive findings with clinical use in people with overt HE but further work is needed.
  • L-carnitine: several potentially beneficial mechanisms of action have been proposed in ammonia toxicity; some positive early findings in people but more work is needed. 
  • Prebiotics, probiotics and synbiotics: controversy in the evidence base in people and further well-designed large-scale clinical trials are needed.

Application to veterinary emergency and critical care

“HE is a relatively common but potentially life-threatening complication of hepatobiliary disease in dogs and cats. Veterinarians working in emergency or critical care settings must be able to promptly recognize, diagnose, and manage this condition. Although increased blood ammonia concentrations strongly suggest HE, it is important for clinicians to be aware of the limitations of this diagnostic tool. It is also essential that predisposing factors are quickly identified and addressed and that appropriate supportive care is provided.”

“Although there are several well-established treatments for HE in dogs, none of them are supported by robust scientific evidence. Clinical trials of the drugs currently used to treat HE are needed to help optimize treatment protocols.”

Papers mentioned in this episode:

Fryer KJ, Levine JM, Peycke LE, et al. Incidence of postoperative seizures with and without levetiracetam pretreatment in dogs undergoing portosystemic shunt attenuation. J Vet Int Med 2011. 25(6):1379–1384.

Lidbury JA, Cook AK, Steiner JM. Hepatic encephalopathy in dogs and cats. J Vet Emerg Crit Care 2016. 26 (4):471-487.

Lidbury JA, Ivanek R, Suchodolski JS, Steiner JM. Clinical feature of hepatic encephalopathy in dogs: 80 cases (1991–2011). J Vet Int Med 2012. 26(3):781 (Abstract).

Mehl ML, Kyles AE, Hardie EM, et al. Evaluation of ameroid ring constrictors for treatment for single extrahepatic portosystemic shunts in dogs: 168 cases (1995–2001). J Am Vet Med Assoc 2005. 226(12):2020–2030.

Proot S, Biourge V, Teske E, Rothuizen. Soy Protein Isolate versus Meat-Based Low-Protein Diet for Dogs with Congenital Portosystemic Shunts. J Vet Int Med 2009. 23(4):794-800.

Rothuizen J, van den Ingh TS. Arterial and venous ammonia concentrations in the diagnosis of canine hepato-encephalopathy. Res Vet Sci 1982. 33(1):17-21.

Taboada J, Dimski DS. Hepatic encephalopathy: clinical signs, pathogenesis, and treatment. Vet Clin North Am Small Anim Pract 1995. 25(2):337–355.

Tobias KM, Rohrbach BW. Association of breed with the diagnosis of congenital portosystemic shunts in dogs: 2,400 cases (1980–2002). J Am Vet Med Assoc 2003. 223(11):1636–1639.

[This podcast is closely aligned with the MedEdLIFE Research Collaborative's Quality Checklist for Podcasts.]
 

Tweet: Check out FREE audio podcasts from @VetEmCC http://ctt.ec/UqL8b+ Also available in iTunes/Stitcher. #veterinary #podcast

Activated Charcoal

*** If you find these podcasts useful and interesting, PLEASE click on the iTunes icon below, then the "View in iTunes" blue link, and then rate and/or review the podcast. That will be really great and much appreciated. Thank you! ***

Listen to Stitcher
Subscribe on Android

What is activated charcoal and how is it meant to work?

Form of carbon processed and treated chemically to create a large number of small pores which increase available surface area for binding to other substances, i.e. microporosity increases adsorptive capacity.
Adsorbent, i.e. poison molecules adhere to its surface
Not absorption whereby the poison molecules would dissolve into and permeate the activated charcoal

Activated charcoal fed to animals that have ingested poisons; not absorbed or metabolised itself, instead binds to some/most of the poison still in the gastrointestinal tract
Charcoal-poison mixture then excreted in faeces
Gastrointestinal decontamination minimises systemic toxin absorption
Considered core part of management of small animal poisoning

Which poisons does activated charcoal adsorb well?

What sorts of substances does activated charcoal bind most avidly to?
From a clinical point of view, are there poisons for which we should be using it versus ones for which we shouldn’t?
Is there any evidence about the relative adsorbent capacity of activated charcoal for different small animal poisons?

Adsorptive capacity likely dependent on/influenced by poison-specific factors, e.g. size and polarity of molecules, degree of ionisation etc.

Bates N, Rawson-Harris P, Edwards N. Common questions in veterinary toxicology. J Sm Anim Pract 2015. 56:298-306:

“The binding of activated charcoal has not been tested against all (or even many) drugs and chemicals, but is known not to significantly adsorb a number of substances such as acids and alkalis, alcohols and glycols (ethylene glycol), metals (e.g. iron, lead), oils and petroleum distillates (e.g. white spirit) and detergents.”

However no references cited.

Use of activated charcoal generally not recommended for caustic or corrosive substances due to apparent lack of efficacy; however unable to find good quality evidence.

Should we be using activated charcoal at all?

Some debate!
  
[Human medicine] The American Academy of Clinical Toxicology (AACT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) position paper:

"Single-dose activated charcoal should not be administered routinely in the management of poisoned patients...[as]... there is no evidence that administration of activated charcoal improves clinical outcome."

But…a lack of evidence of a beneficial effect on clinical outcome is not the same thing as evidence of a lack of beneficial effect on clinical outcome.

Veterinary patients?

“What you can know for sure – unless I failed to find them – is that there are no good quality prospective randomised controlled trials in clinical canine and feline patients evaluating the impact of activated charcoal on clinical outcome.” (Shailen Jasani)

Multiple variables to be studied, e.g.

  • Individual poisons
  • Different doses of the same poison
  • Whether or not emesis was induced
  • Time from exposure to administration of activated charcoal
  • Etc.

Risk/Cost-benefit assessment: general perception is low risk and cheap with potential for some/considerable/life-saving benefit.

Relative lack of antidotes and other treatment modalities (e.g. haemodialysis, plasma exchange) in veterinary versus human medicine

Contraindications and potential adverse effects

Not risk free albeit clinically significant adverse effects considered very uncommon/rare
Use common sense – e.g. do not administer orally to patients at increased risk of aspiration due to neurological compromise

Clinically significant acute hypernatraemia:

Most commonly cited mechanism is that activated charcoal draws water osmotically into the GI tract; this is then voided causing volume depletion.
Patients may have other co-existing causes of water loss plus reduced water intake
More likely with concurrent cathartic administration – but anecdotally reported with use of activated charcoal alone

Minimising the risk:

  • Ensure patient is adequately (re)hydrated beforehand
  • Tailor approach with respect to blood testing of hydration parameters and use of fluid therapy to individual patient based on risk assessment (e.g. very young or very old patients, existing vomiting, etc.)
  • Patients discharged on multidose activated charcoal following successful induction of emesis: advise clients to ensure free access to water and to contact clinic if any ongoing vomiting or clinical concern; liberal approach to administering antiemetic/antinausea agent before discharge.  
  • Avoid activated charcoal if ingested poison is known/suspected to be one that (potentially) causes hypernatraemia (e.g. homemade play dough); use cautiously for poisons which may induce diuresis (e.g. theobromine (chocolate)).

Pay attention to dose being dispensed:

  • Recommended dose range 0.5-8 g/kg depending on resource consulted
  • Less precise/more liberal empirical dosing may be acceptable for bigger and asymptomatic patients
  • Calculate and measure out doses in patients where there is clinical/hydration status concern; use low end doses and well-spaced dosing intervals for multidose therapy.

Avoid activated charcoal if possibility of gastrointestinal perforation, obstruction or ileus
Some debate about need to avoid if oral medications or antidotes needed
Avoid if gastrointestinal endoscopy or surgery is likely in the near future
Constipation may occur with multiple dose therapy

Timing of administration

Ideally administer as soon as possible after toxin ingestion; efficacy decreases the more time passes.
Many resources suggest not to administer activated charcoal if more than 2 hours have elapsed; this author typically suggests a longer more liberal time frame.
In reality likely to depend on multiple factors, e.g.

  • Rate of toxin absorption from gastrointestinal tract
  • Presence of food
  • Type of preparation e.g. delayed or sustained release?
  • Whether enterohepatic circulation occurs
  • Other factors influencing gastrointestinal motility and function

Paper mentioned in this episode:

Bates N, Rawson-Harris P, Edwards N. Common questions in veterinary toxicology. J Sm Anim Pract 2015. 56:298-306.

[This podcast is closely aligned with the MedEdLIFE Research Collaborative's Quality Checklist for Podcasts.]

Tweet: Check out FREE audio podcasts from @VetEmCC http://ctt.ec/UqL8b+ Also available in iTunes/Stitcher. #veterinary #podcast