Colitis/diarrhoea in adult horses (ECB week 4)

Question 1

How much water does the average horse secrete into the proximal GIT per day?

Answer 1

125L
Most passes through SI and is absorbed by the large colon

Question 2

How much faeces does a normal average 500kg horse produce?

Answer 2

8-10 droppings per day
= 10-15kg per day (75% water)

Question 3

What is diarrhoea?

Answer 3

Increased volume/frequency and fluidity of faeces

Question 4

How much water can horses lose with diarrhoea?

Answer 4

Can be up to 90-100L per day

Question 5

What are the main losses in diarrhoea?

Answer 5

Water
Electrolytes
Protein

Question 6

What are the mechanisms of diarrhoea?

Answer 6

1. Malabsorption - often related to inflammation -> loss of absorptive cells/tight junctions
2. Increased secretion - bacterial exotoxins (e.g. Salmonella), inflammation
3. Osmotic overload - if given epsom salts (Mag sulphate), feeds, maldigestion
4. Abnormal motility - inadequate mixing/time for absorption, e.g. after stress/transport
5. Extravasation of fluid (oedema) - hydrostatic, colloid osmotic, capillary premeability, reduced lymph drainage

Question 7

When does diarrhoea come following the onset of colitis?

Answer 7

Often 1-2 days after initial onset of signs e.g. dullness (takes take for fluid in gut lumen to reach rectum)

Question 8

Definition of colitis?

Answer 8

Any inflammation of colon +/- caecum (should actually call it typhlocolitis)

Question 9

What are the 2 key factors that help you differentiate a colitis from a typical colic at the first visit? What 2 other main differentials for these 2 factors are there?

Answer 9

Pyrexia and leucopenia

Mild colic case with either of these - be suspicious of colitis, enteritis or peritonitis

Question 10

How do acute colitis cases typically present?

Answer 10

Often just dull, rather than active colic (foals different - usually severe colic signs with enteritis/colitis)

Question 11

What are the local effects of colitis?

Answer 11

Inflammation from injury, pathogens, toxins
-> Vasodilation/vascular permeability -> mural oedema, osmotic diarrhoea
-> Pain (activation of C fibres in gut wall) - dull/low grade usually
-> Altered motility - hypermotility common with decreased transit time
-> Malabsorption and hypersecretion - loss of proteins, Na, Cl, K, water

Question 12

What happens with endotoxaemia/SIRS with colitis?

Answer 12

Molecules and endotoxins released my pathogens and commensal microbiota (e.g. endotoxin of gram negative cell walls) -> released into inflamed colon -> enter hepatic portal vein in large quantities -> overwhelm the normal clearance mechanism of the liver -> enter systemic circulation -> SIRS

Key target site of these toxins as part of SIRS is endothelium of capillaries -> activation of neutrophils -> release nasty enzymes and reactive oxygen species -> damage to endothelium walls -> increased permeability -> capillary leak -> fluid and protein leaves the vessels -> oedema

Cardiovascular system also affected - widespread inappropriate vasodilation (e.g. get injected mucous membranes) -> maldistribution of blood, reduced cardiac contractility, DIC -> low circulating blood pressure, oedema and microthrombi -> poor perfusion of organs -> tissue hypoxia -> multi organ failure (including laminitis)

Question 13

What are the clinical signs/indicators that SIRS is happening with acute colitis?

Answer 13

Increased HR/RR
Slow CRT (or very quick)
Injected MM
Weak pulses
Cold extremities
Increased creatinine (due to decreased perfusion of kidney) and lactate

Question 14

What history/signalment to consider for acute colitis case when making differentials?

Answer 14

Age - cyathostominosis in young horses (late winter-early spring)
Recent antimicrobials/anthelmintics/NSAIDs
Diet change
Stressors - transport/hospitalisation/surgery etc

Question 15

How to assess dehydration with diarrhoea?

Answer 15

Demeanour
Heart rate
MM (pale and dry is appropriate response to dehydration or hypovolaemia, injected is inappropriate response)
CRT
Skin tent, sunken eyes
Urine production - if none passed for several hours suggests poor perfusion of kidneys
Oedema

Question 16

What lab findings are typical for acute colitis?

Answer 16

Leucopenia - particularly neutropenia and degenerative left shift
Increased PCV
Pre-renal azotaemia - match with high USG (>1.015) - requires IVFT (AKI also possible)
Low Na, Cl, K and Ca
Low Albumin/protein - can be normal while haemoconcentrated, drops following fluid resuscitation
Increased lactate - can guide need for IVFT
Mild increases liver/muscle enzymes (esp CK and GLDH) due to reduced perfusion, ischaemia, inflammatory cytokines

Question 17

Why is leucopenia characterisitic with SIRS in acute colitis?

Answer 17

Neutrophils have been sequestered into large colon
Neutrophils also marginated in all organs

Question 18

How can PCV and lactate be used as prognostic indicators for acute colitis/SIRS? What other factors reduce likelihood of survival?

Answer 18

PCV >45% = 3.5x less likely to survive
Lactate at admission = less likely to survive if >4.3mmol/L (se 72%, sp 80%)
Lactate 6-8hrs after initial fluid therapy = less likely to survive if >2 (se and sp as above)
From Peterson paper TVJ 2016

AM administration before colitis: 4.5x less likely to survive
Azotaemia at admission (creatinine >180) and HR >60 at admission associated with non survival

Question 19

What is ultrasound used for in acute colitis cases? What might be seen?

Answer 19

Wall oedema and altered motility
Usually colitis associated with reduced motility, but sometimes have thickened hypermotile gut
Useful to investigate differentials e.g. peritonitis
Sometimes will see a displacement associated with thickened colon - have to be careful determining whether thickened wall is due to colitis, or due to venous congestion with displacement (e.g. colon torsion will have thickened wall)
Colon content is usually dry/gas so can’t see to the opposite side - if hypersecretion/filled with fluid can see further with fluid in between

Question 20

What does this ultrasound image show?

Answer 20

Excessive fluid in large colon - colitis

Question 21

What do these ultrasound images show?

Answer 21

Left = thickened caecum wall
Right = thickened RDC wall, but also displaced colon between right liver lobe and diaphragm

Question 22

What is the best test for sand colic/colitis?

Answer 22

Radiography
Glove test is quite crude - can have lots of sand with negative result
Scoring system available - some sand is ok

Question 23

How many colitis cases end up ‘idiopathic’ with no found cause?

Answer 23

> 50%
May be ‘dysbiosis’ cause - but cause or effect?

Question 24

What faecal analysis to do for an acute colitis case?

Answer 24

Salmonella - Intermittently shed. PCR or culture - low sensitivity, high specificity. Advantage of culture is sensitivity testing. Advantage of PCR is increased sensitivity and speed of results. 3-5 samples 12-24hrs apart to improve sensitivity and to declare horse ‘negative’

Clostridium difficile/perfringens - Challenging as all options low sensitivity and some tests don’t tell us significance. Toxin ELISA - most useful information, low sensitivity. PCR for toxigenic gene - but are these expressing toxin? Culture limited use - are these toxigenic?

Coronavirus PCR - Have been some outbreaks mostly in the States. Usually milder signs compared to Salmonella - dull, mild colitis, pyrexia. Worth testing for routinely.

WEC - results difficult to interpret with watery diarrhoea

Question 25

How significant is Clostridium perfringens in adult diarrhoea?

Answer 25

C perfringens very common in normal adults, but also with colon dysbiosis - primary or secondary? Likely not very significant to acute diarrhoea, but if find toxigenic form might be significant

Question 26

Is serology for cyathostomins useful for acute colitis?

Answer 26

Validated in normal horses, affected by low protein But seems to correlate with clinical suspicion of larval cyathostominosis Worth testing

Question 27

Why is acute colitis generally more serious than chronic?

Answer 27

Fluid intake does not match fluid requirements (and requirement is even higher than normal as SIRS affects blood circulation)

Question 28

What to estimate for the cost of acute colitis treatment with SIRS?

Answer 28

Leahurst estimate £4000-6000 for the average idiopathic case

Question 29

What is the short term mortality rate (not making it out of hospital) for acute colitis?

Answer 29

25-37%

Question 30

What are the principles of management of acute colitis?

Answer 30

Restoration/maintenance of circulating volume (i.e. fluid therapy to correct hypovolaemia and then maintenance and replacement of losses) Analgesia Reducing colon inflammation - anti-inflammatories Prevent/manage effects of SIRS Restore colonic mucosa Nutrition Biosecurity (All important, but top 3 are main priorities)

Question 31

What are the aims of fluid therapy for acute colitis?

Answer 31

Restore circulating volume Correct abnormalities of electrolytes, acid base and colloid osmotic pressure (albumin is main determinant) Maintenance fluids Replace ongoing losses - gut lumen/diarrhoea/oedema

Question 32

Why are acute colitis cases at a high risk of developing thrombophlebitis?

Answer 32

Hypercoaguable state with SIRS

Question 33

How to reduce risk of thrombophlebitis with acute colitis case when placing catheter?

Answer 33

Minimise vein trauma when placing catheter - experienced person placing Ensure sterility (white part of catheter must not be out of skin), including for local anaesthetic and sutures - clip and scrub areas where sutures will go (don’t want to introduce infection under the skin in these cases)

Question 34

What size catheter to use for acute colitis fluid therapy?

Answer 34

14G most commonly Can also use 10G temporarily if need to give large volumes quickly E.g. if severe hypovolaemia - place 14G long stay on one side, 10G other side but only for 1-2hrs (risk bilateral phlebitis) and then pull short stay Use short, high flow extension sets

Question 35

What should you do if you start seeing a thrombus forming around a jugular catheter on ultrasound?

Answer 35

Ideally pull catheter as soon as starts to form Place catheter elsewhere (ideally not the other jugular as bilateral jugular thrombophlebitis can lead to airway obstruction and need tracheostomy) - use lateral thoracic vein, or cephalic vein

Question 36

What can be seen here?

Answer 36

Thrombus forming in left image (right is normal) Horse has engorged blood vessels and swelling of neck if bilateral jugular thrombophlebitis - often need treachesotmy with airway obstruction

Question 37

Which fluid to use for replacement and maintenance therapy for adult horses with acute colitis? How does it compare to plasma content of electrolytes?

Answer 37

Hartmann's - not far off normal plasma content (bit high on Cl, bit low on Na, K could be a bit higher). For maintenance after replacement therapy, would ideally supplement with KCl, Ca and Mg (esp if longterm therapy). Normosol-R is actually slightly better option but hard to get hold of and often only 1L bags 0.9% NaCl not suitable replacement therapy as too high Na and CL

Question 38

How quickly are crystalloid fluids lost from the intravascular space?

Answer 38

70-80% lost from intravascular space in 30-60 mins (less in hypovolaemia, more in reduced COP/capillary permeability)

Question 39

What level of chronic hypoNa must we correct slowly? At what maximum rate? Why?

Answer 39

Chronic hypoNa (<120mmol/L) should be corrected slowly Max 0.5mmol/L/hr To avoid osmotic demyelination of thalamus/pons Ideally monitor and aim for this, but practicalities can be difficult

Question 40

Hypertonic crystalloids - Example of one to use? Purpose? How quickly works? What to follow with? Other benefits? Contraindications?

Answer 40

Vetivex 20 (7.2% NaCl) Very effective at rapidly expanding plasma volume - borrows fluid from extravascular space Increases plasma volume by 3x volume infused Maximum effect after 20-60 mins Causes intracellular dehydration Must be followed by large volumes of isotonic crystalloids (10x volume of hypertonic given) Horse will be very thirsty! Also positive inotrope - improves contractility Reduces endothelial/tissue oedema Reduces neutrophil activation Contraindicated if: hypernatraemia, hyperchloraemia (both rare in colitis cases), overcorrection of severe hypoNa, uncontrolled haemorrhage (e.g. post foaling haemoabdomen)

Question 41

Can plasma be useful for acute colitis?

Answer 41

Yes - useful for hypoalbuminaemia with some protective effect on glycocalyx but still issue of leaking albumin and tissue oedema But expensive and would need 8-10L for 500kg horse to really have a significant benefit on colloidal oncotic pressure (too costly for most people) Monitor for transfusion reactions

Question 42

Are synthetic colloids useful in acute colitis?

Answer 42

Whole oncotic pressure system breaks down with SIRS with loss of endothelium barrier and loss of albumin So colloids less useful to give

Question 43

Why have synthetic colloids gone out of favour in humans?

Answer 43

Issues with coagulopathies and renal disease

Question 44

What is the 'fluid challenge' method of giving fluid therapy to an acute colitis/SIRS case?

Answer 44

Bolus of Hartmann’s: 20ml/kg (10L for 500kg horse, 1L for 50kg foal) given over 20-30 mins (takes about this time for 14G catheter) or as fast as possible Reassess parameters - if no improvement, repeat (maximum of 4 boluses) Once have replaced the fluid deficit and things have improved, move onto maintenance rate If severe hypovolaemia: hypertonic saline 2-4ml/kg (1-2L) rapidly and then follow up with Hartmann’s This is Harry Carslake's preferred method

Question 45

What is the traditional dehydration estimation method for fluid therapy for acute colitis/SIRS?

Answer 45

Estimate dehydration (5-15% BW, <5% not detectable, >15% unable to sustain life) and replace fluid deficit over 4-6hrs E.g. 500kg horse with 10% dehydration: 50L/5hrs, plus 2ml/kg/hr maintenance = 55L over first 5hrs

Question 46

Levels of dehydration in the horse?

Answer 46

Question 47

Rate of maintenance fluid therapy for acute colitis?

Answer 47

2ml/kg/hr plus ongoing losses (but (difficult to assess diarrhoea volumes, generally titrate rate based on HR, lactate etc)

Question 48

Objectives of fluid therapy for acute colitis? How to assess this?

Answer 48

Restore tissue perfusion and Correct electrolyte and acid/base abnormalities Repeat clinical assessments regularly - not looking for total normalisation, but looking for improvements following fluid therapy Heart rate - looking for some decrease Urination - have they urinated since starting fluids? Improved mentation Extremity temperatures Blood lactate, PCV, TPP CRT, arterial blood pressure (not practical in horses), jugular fill

Question 49

What to be careful of with fluid therapy of acute colitis? When should you slow down/stop?

Answer 49

Very easy to overdo fluids and risk oedema formation - colitis cases normally already have oedema, don’t want to worsen it - causes multiorgan dysfunction if not already present Difficult to assess oedema formation and compartment syndrome Increased respiratory rate early sign of pulmonary oedema - consider whether overdoing fluids, esp if renal failure present If excessive urine production or USG <1.020, suggests overdoing, so reduce fluids unless azotaemia Use objectives as end points as above (HR, lactate etc) - move onto maintenance rate once these are improving

Question 50

What analgesia and anti-inflammatories to use for acute colitis/SIRS?

Answer 50

NSAIDs: Flunixin is mainstay - if NSAID toxicity suspected then avoid flunxin and phenylbutazone and consider use of firocoxib/metacam instead NSAIDs are not good for restoration and healing of mucosa (inhibit PGE2 and PGI2, so inhibit mucosal repair), but benefits for anti-inflammatory effect and SIRs and analgesia and outweighs the negative effects - antipyretic, analgesia, anti-inflammatory, antisecretory in colon Care with hypovolaemic animals - kidney perfusion NSAIDs more effective if given before the onset of SIRS/endotoxaemia, but rarely in position to do this Paracetamol 20-30mg/kg BID Opioids - care with impaction risk, but realistically unlikely a problem in colitis cases Ketamine IM/infusion Lidocaine infusion (Above 3 not realistic to use on yard, need hospital setting) Corticosteroids? Judicious use of dexamethasone Highly controversial Potent anti-inflammatory, so short course can be useful (e.g. single dose dex) Downsides: Immunosupprssion, mucosal healing, effect on insulin resistance Bismuth subsalicylate sometimes used (Pepto-bismol) 500ml q4-6hrs - anti-inflammatory

Question 51

Should you use antimicrobials for acute colitis/SIRS?

Answer 51

Controversial Generally don’t use - Harry Carslake says tends to steer clear Only if there is a specific pathogen to target (Salmonella - enrofloxacin, Clostridia - penicillin, or metronidazole better, Lawsonia - tetracycline) Even still controversial for Salmonella - AMs worsened outcome in some studies Already massive dysbiosis in the colon - AMs will disrupt colon flora in normal horses

Question 52

Which absorbents/probiotics to use for acute colitis?

Answer 52

Smectite ‘Biosponge’: binds C diff and perfringens toxins in vitro, 1g/kg SID-BID Probiotics: minimal evidence, Saccharomyces boulardii decreased duration/severity of colitis (Desrochers 2005) - so if using a probiotic, use this one

Question 53

If doing faecal transfaunation/faecal microbial transplanation, what to do first? Paper?

Answer 53

Pretreat with omeprazole to reduce acidity in stomach Use healthy donor ‘Mullen et al 2016 EVE paper Tend to use more in chronic cases

Question 54

How to do laminitis prophylaxis for acute colitis/SIRS?

Answer 54

Cryotherapy (has good evidence to support it but all the studies used ice up to lower cannon). Labour intensive and difficult practically. Can use 5L fluid bag taped over feet with crushed ice/water slurry (cubes can cause pressure and cold burns) but melts quickly and not reaching lower cannon. Soft ride ice boots better but still difficult to maintain on horse - don’t tolerate very well. Heel/frog supports, make sure not long toes Low glycaemic feed - will be insulin resistant with sepsis

Question 55

What other anti-SIRS treatments can be used for acute colitis?

Answer 55

Heparin: Reduces hypercoagulable effect of SIRS -> decrease thrombosis and ischaemia in multiple organs Low molecular weight (Fragmin) preferred over unfractionated - fewer side effects e.g. anaemia Give IV, or can give SC - can be sore and get haematomas with SC Polymyxin B: Antibiotic - works by complexing lipid A of lipopolysaccharide (specific to gram negative bacteria) On WHO protected list Get as a chemical formulation from Sigma - hard to get hold of Give IV Hyperimmune plasma/lidocaine/pentoxyfylline/omega 3 FAs - all have some evidence, but not routinely used

Question 56

What drugs can be used for mucosal repair for acute colitis?

Answer 56

Misoprostol: Synthetic PGE analogue Anti-inflamamtory effect and beneficial for mucosal healing 5ug/kg PO BID Occasional side effects: colic, diarrhoea, sweating Abortogenic - care handling/dispensing Harry Carslake uses quite a lot - rarely sees side effects Psyllium 1 cup BID (lower dose than is used for sand colics) Increases production of SCFAs (particularly butyrate) Sucralfate 20mg/kg PO BID-QID and/or omeprazole

Question 57

What to do if suspect cyathostominosis as cause of acute colitis?

Answer 57

Diagnosis is difficult Stabilise SIRS/hydration first Don’t worm whilst signs of SIRS (e.g. hypovolaemia, clear systemic inflammatory response) - concern is death of worms will lead to further damage of colonic wall when it lest needs it Once stabilised, give moxidectin with 3-4 days of dexamethasone

Question 58

What nutrition to do for acute colitis case?

Answer 58

Often poor appetite, need to prevent negative energy balance (not as big problem in adults as foals) Minimise non structural carbohydrates (sugar/starch) - colon is best fed with structural carbohydrates/cellulose/fibre/forage Minimise mechanical and physiological load on colon: Highly digestible/low residue forage (want more cellulose, less lignin = leafy, less stem hay/forage) Complete pelleted feeds are good e.g. TopSpec Fibre Plus cubes - highly digestible fibre and protein, with extra macro and micronutrients Frequent small meals Corn oil for extra calories if needed: 20ml BID, building up to 50-60ml BID

Question 59

Which cases with diarrhoea to isolate?

Answer 59

Leahurst isolate if: 2 or 3 out of: pyrexia, leucopenia and diarrhoea (but this is not a 100% fail safe) Plus clinician discretion e.g. recent administration of AMs Harry will be more likely to isolate even if just dull

Question 60

When to release a horse from isolation?

Answer 60

Decide on clinic basis how to determine release from isolation - traditional is 5 negative Salmonella cultures but reduced prevalence of Salmonella shedding in Uk compared to America - likely use PCR and less samples

Question 61

When to consider euthanasia of acute colitis case?

Answer 61

Majority will get better, but costs are significant Some come in not too bad but then dramatically deteriorate suddenly with severe colic signs - uncertainty why this happens, but likely due to development of severe inflammation and ischaemia reaching point of being very painful Usually unable to manage this pain and requires euthanasia Sepsis related laminitis very difficult to manage and may need euthanasia If unable to adequately improve perfusion despite fluid therapy - need vasopressors etc (next level of treatment) - euthanasia likely due to spiralling costs - frank conversation with owner

Question 62

Plan for managing an acute colitis case on a budget (e.g. £800) in the field/yard stable?

Answer 62

Priority is fluids to treat the hypovolaemia IV probably too expensive, unless bolus possible 10G short stay catheter - get 10L in as fast as possible 10% dehydrated = 50L deficit! Enteral fluids: Not as suited for cases with GI compromise (inflamm and ileus will reduce absorption), but worth a try as long as no reflux Would normally give 8L to adult healthy horse 90% of water is emptied from stomach in 15 mins with normal motility Dehydrated horse can drink >50ml/kg in 30 mins = 25L in 500kg horse So give 8L, then another 8L 30 mins later If possible return 1-2h later and repeat the same Indwelling tube? Use muzzle - max 20ml/kg/hr (start slower!). Care with owners doing this - can be dangerous. Best to return and put the fluids in yourself. Use iso/slightly hypotonic enteral fluids = 7.5ml NaCl/L of water or 3ml NaCl + 3ml ‘LoSalt’/L of water (Losalt provides some K) Hopefully SI is working and will absorb most of the water Dexamethasone 0.06mg/kg IV single dose NSAIDs: bute much cheaper than flunixin (especially orally) - although always reach for flunixin, probably not huge difference Ice feet if owner has time (free but time consuming)/frog supports Biosponge/absorbent in NG fluids Metronidazole if suspect Clostridial diarrhoea - expensive so will blow budget quickly, so probably avoid Anthelmintics - consider once stabilised PCV/TP/USG most useful blood tests for monitoring fluids - relatively cheap (great if they do catch urine!) Also lactate if machine in car - have to measure within 20 mins of taking sample Monitor urination, HR, demeanour Earliest sign of pulmonary oedema = increased RR Biosecurity difficult in a field. Tell owner to check temp of in contacts. PPE for owner. Euthanasia if: Deteriorating CV status or uncontrollable colic pain. Unless definitely going to live, remember budget to treat = total budget minus cost of euthanasia (can take up a large part of budget)