Clinical Equine Reproduction - Care of Sick Neonate

Question 1

What is a red bag delivery? What consequences does it have?

Answer 1

Premature separation of chorion from uterine epithelium –>

First observe red velvety chorionic surface (vs. smooth amnion in normal parturition) –>

Disruption of oxygen exchange surface –>

Foal may be clinically normal or show signs of neonatal maladjustment

Question 2

What is a common syndrome in foals that you oftne get is they have a red bag delivery?

What clues might the foal have that points you in this direction?

Answer 2

After red bag delivery - What can be seen?

• Perinatal asphyxia syndrome
• Ataxia, uncoordinated
• Head pressing
• Can it see properly? Hard to tell if it cannot see or if it just cannot move properly – but certainly not aware of its surroundings and if you left, it would circle, no interest in mare and would not be able to find udder to suckle

Question 3

What are some other names for neonatal maladjustment?

Answer 3

•Many names

–Hypoxic Ischemic Encephalopathy (HIE)

–Perinatal Asphyxia Syndrome

–Dummy foal

–Barker

–Wanderer

Question 4

What is the problem with neonatal maladjustment syndrome (perinatal asphyxia syndrome)?

Answer 4

• Variable clinical signs from subtle to coma
• Difficult thing about this is that its really variable – some just look a bit slow, through to coma, seizure activity and death…

Question 5

What are some of the theories behind neonatal maladjustment (perinatal asphyxia syndrome) that can go on to cause neuronal injury?

Answer 5

Question 6

With neonatal maladjustment (perinatal asphyxia syndrome), what can be higher in cells? What does this cause?

What else is activated?

What can hypoglycaemia do?

Answer 6

•Increased intracellular calcium and sodium

–Failure of energy dependent cell membrane ion pumps

–Cellular swelling

• Calcium accumulation activates calcium dependent phospholipases, NO synthase and proteases
• COX 2 activation increases production of inflammatory lipid mediators
• Hypoglycemia exacerbates brain injury

Question 7

With neonatal maladjustment (perinatal asphyxia syndrome) what is the role of neurosteroids?

Answer 7

• Neurosteroids (progestagen compounds) are neuromodulatory and are integral fro the transition to extra uterine life
• NMS can be induced in normal foals by administration of allopregnanolone1
• Depression compatible with NMS but without the hypoxic-ischemic event
• Reversion to fetal consciousness with the ‘squeeze technique’

Question 8

In a foal with neonatal maladjustment (perinatal asphyxia syndrome), the foal is ambulatory and shows no seizure activity yet.

How can we control cerebral oedema and inflammation?

Answer 8

–Mannitol and hypertonic saline (7.2%)

–NSAIDS

–Dimethyl sulphoxide (DMSO) - free radial scavenger – industrial chemical

–Glucocorticoids? Debate goes on – if inflammatory, might help, but if free radical damage might not help!

Question 9

In a foal with neonatal maladjustment (perinatal asphyxia syndrome), the foal is ambulatory and shows no seizure activity yet.

How can we combat ongoing oxidative damage?

Answer 9

–DMSO - free radial scavenger – industrial chemical

–Magnesium - anti-oxidants and decrease damage to nerve cells

–Vit C and E

Question 10

In a foal with neonatal maladjustment (perinatal asphyxia syndrome), the foal is ambulatory and shows no seizure activity yet.

What are out treatment goals overall?

Answer 10

Control cerebral oedema and inflammation

–Mannitol and hypertonic saline (7.2%)

–NSAIDS

–Dimethyl sulphoxide (DMSO)

–Glucocorticoids? Debate goes on – if inflammatory, might help, but if free radical damage might not help!

Combat ongoing oxidative damage

–DMSO - free radial scavenger – industrial chemical

–Magnesium - anti-oxidants and decrease damage to nerve cells

–Vit C and E

• Provide metabolic requirements
• Address any concurrent medical conditions
• Squeeze
• Nutritional support

Question 11

In a foal with neonatal maladjustment (perinatal asphyxia syndrome), what is the theory behind using the ‘squeeze’ tehcnique?

Answer 11

If mild signs – if you squeeze them, mimic pasage of foal through maternal birth canal so get rid of some of these signs. Some success with mild cases and sometimes it will reduce clinical signs but in severely affected cases – wont do much!

Wrap rope around neck and twice around thorax – similar to making cow lie down

Mimics pressure through birth canal and usually leave on for 15-20 minutes

Good tool if you have a foal that you need to do stuff too but you just want them to lie still for a minute! They lie down and go a bit sleepy – rather than having to use drugs

Question 12

With neonatal maladjustment (perinatal asphyxia syndrome), how can we combat the concurrent issue of failure of passive transfer?

Answer 12

–Plasma transfusion

–colostrum

Question 13

With neonatal maladjustment (perinatal asphyxia syndrome), how can we combat the issue of concurrent sepsis - what can cause this sepsis?

Answer 13

•Concurrent sepsis (pre-partum if mare had uterine infection)

–If return of inutero placentitis that the foal may also have blood born sepsis

–Down more on wet umbilicus – increased likeliness of bacteraemia

Question 14

Ina foal with neonatal maladjustment (perinatal asphyxia syndrome), how do we provide them with nutritional support?

This case is ambulatory but suck relfex if poor. Can tolerate enteral nutrition.

Answer 14

•Options

–Colostrum – little bit old for colostrum (as about 18h by now) but yes, if mare has it – milk mare and give it to the foal!

–Wont be able to nurse for 3 or 4 days likely…

–Can try bucket or bottle but will be hard for it to

–Total IV nutrition but £££

–Using its gut – as long as doesn’t have ileus, colic or reflex – so placed enteral feeding tube

•How much

–A normal foal might eat 20% of the BW per day – so if 50kg foal, that’s about 10L – usually drink about 6x per hour which is not something we can mimix

–Hand strip mare if she has enough

–Milk replacer

–In sick neonate – they might not be able to tolerate 20% so might aim for 10% - roughly 400ml/every 2h

• Mare’s milk
• Hand strip in to a clean bowl
• Milk replacer (3/4 strength)
• Healthy foal will consume 20-25% body weight per day (10L/day)

–Nursing up to 6 times per hour

•Compromised neonate aim for 10% body weight (5L in 24 hours)

–400mls every 2 hours

–Start at 200mls/2hr and increase over first 24 hours

Question 15

Why is increased fibrinogen significant in a neonatal foal?

Answer 15

Increased fibrinogen – acute phase protein, takes a while to get going to high levels – so if you see that this is high in a neonate, then this foal has probably had an in-utero infections in order to get this response to be high at this age

Question 16

What is SIRS?

Answer 16

• 2 or more of
• Increased or decreased body temperature
• Tachycardia
• Tachypnea
• Leukocytosis, leukopenia or >10% band neutrophils

Question 17

How do we define severe sepsis?

Answer 17

• SIRS plus organ dysfunction or hypo perfusion
• Lactate>4mmol/l

Question 18

How do we define septic shock?

Answer 18

•Severe sepsis refractory to volume resuscitation

Question 19

What is the pathophysiology of sepsis?

Answer 19

Pathogen associated molecular patterns (PAMPS) e.g. LPS lipotechoic acid, flagellin or damaged associated molecular patterns (DAMPS) e.g. extracellualr DNA and RNA, heat shock proteins –>

Pattern recognition receptors eg TLR-4 on macrophages

–>

Pro-inflammatory cytokines TNFalpha, Il-1B, IL-2, IFN-gamma

–>

Acute phase protein production, endothelial cell damage

Question 20

With sepsis, you get microvascular thrombosis and neutrophil chemotaxis - what does this lead to?

Answer 20

Microvascular thrombosis and neutrophil chemotaxis –>

Increased capillary permeability –>

Hypotension –>

Multi-organ dysfunction

Key things – active of coagulation cascade, change in membrane permeability, hypotension and if we don’t restore perfusion to tissues – will get MODS and once we get to this stage, death is usually the outcome!

Question 21

In a foal with neonatal sepsis, what are out initial stabilisation and diagnostics?

Answer 21

• Gloves and aprons etc
• Warm dry clean bed
• Aseptically placed jugular catheter (in this case over the wire MILA 2 lumen)

–Wrapped – as foals are good at rubbing things out!

•Resuscitation fluids

–Incremental fluid bolus concept

–20ml/kg (1L for a 50kg foal)

–Up to 4 boluses (initially 1L hyperimmunised plasma and 1L Hartmann’s)

–Multiple ways to volume resuscitate – warm fluids, haartmans, 20mk/kg is rough dose for resus – bag if fluids, squeeze it in, reevaluate after its had 1 or 2 L

•Intranasal oxygen

–Whilst waiting for arterial blood gas results

• Urinary catheter
• Arterial blood gas analysis

Question 22

In a foal with neonatal sepsis - what are the estiamted costs of treatment?

What is their prognosis like?

Answer 22

• Estimated cost of treatment £1000 per day initially (minimum of 72 hours intensive care)
• Prognosis is difficult to predict (even without financial constraints)
• Reported short term survival ranges from 50-70%1

–Outcome has improved significantly over recent years

• Owner elected to pursue treatment
• They are really expensive! Need to keep costs in mind and let owners know this! Will require MIMIMUM of 3 day intensive care

Question 23

In foals with neonatal sepsis, what antibiotics should we give?

Answer 23

• Always take a blood culture of these foals but often have to wait for these results so give:
• Broad spectrum antibiotics (awaiting blood culture)

–Penicillin G 22,000-44,000IU/kg IV q 6hrs

–Plus gentamicin (8-12mg/kg IV q24hrs) – be aware that dose is different in foals (they have larger volume of distribution due to increased body water)

•Product License is for 6.6mg/kg IV

»This is probably an inadequate dose

•Up to 15mg/kg maybe required but requires gentamicin kinetics to be run

–Or ceftiofur 2-10mg/kg IM or IV q6-12hr

Question 24

How does a foals volume of distribution differ to that of an adults?

Answer 24

Be aware that dosages are different in foals (they have larger volume of distribution due to increased body water)

Question 25

In a foal with neonatal sepsis, along side broad spectrum antibiotics, what other drugs should we consider giving them?

Answer 25

•NSAIDS

–Flunixin

•Glucose infusion – as it wasn’t eating

–20kcal/kg/day=1000kcal

–40% Dextrose is 1.4kcal/ml

–26mls/hr

• Insulin infusion
• Hydrocortisone

Question 26

If you have to give a foal with neonatal sepsis parenteral nutrition - what can be give?

What must we ensure we do every 72h?

Answer 26

• Parenteral Nutrition

–50% dextrose

–Amino acids

–+/- lipids

–vitamins

• Dedicated catheter port
• Change fluid lines q72hrs (24hrs with lipids)
• Cleanliness is very important in these cases as they are very sick

Question 27

6 days post admission of a foal with neonatal sepsis, the foal was bright, ambulatory and nursing well.

However WBC remained elevated and fever spikes were noted after cessation of flunixin administration

1. Where are the most likely places for infection to localise after sepsis?

Answer 27

–Umbilicus

–Joints

–Lungs – they often get pneumonia

Question 28

48h old foal. Had normal delivery at home. Was normal at birth – deteriorated at 48h of age

Was ambulatory when arrived. Now appears like this. Systolic heart murmur. PCV 14

What is the most common DD for just this presentation?

Answer 28

Neonatal isoerythrolysis

Question 29

Can you think of 5 causes of icterus in a neonatal foal?

(tip - split inot prehepatic, hepatic and post)

Answer 29

•Prehepatic

–Hemolytic – Neonatal Isoerythrolysis

•Hepatic

–EHV 1 infection in utero

–Tyzzer’s Disease – Clostridium pilliformis

–Maladjustment syndrome – hepatic hypoxia

•Post hepatic

–Congenital defect

–Gastro duodenal ulceration and bile duct occlusion

Question 30

How do we diagnose neonatal isoerythrolysis in a foal?

Answer 30

–Presumptive – just based on clinical picture!

–Minor cross-match (stall-side)

• Mare’s serum plus foal’s blood mixed
• Agglutination – if you have positive antibodies – but destruction of RBCs can be from different things, so if you want to test for these also – have to do the tests below also

–Positive Coombs test

• foal blood + equine polyvalent Coomb’s reagent (IgM, IgG and anti-C antibodies)
• Agglutination only

–Hemolytic cross match – the most sensitive and specific but takes time for results!

• Washed foal RBCs with mare serum plus complement
• Positive if hemolysis or agglutination

Question 31

What is a minor cross-match?

Answer 31

Part of a test for neonatal isoerythrolysis

Mare’s serum plus foal’s blood mixed

Agglutination – if you have positive antibodies – but destruction of RBCs can be from different things, so if you want to test for these also – have to do the tests: positive coombs test & haemolytic cross match

Question 32

What is a positive Coombs test?

Answer 32

Part of a test for neonatal isoerythrolysis

foal blood + equine polyvalent Coomb’s reagent (IgM, IgG and anti-C antibodies)

Agglutination only

Question 33

What is a haemolytic cross match test?

Answer 33

Part of the testing for neonatal isoerythrolysis

Hemolytic cross match – the most sensitive and specific but takes time for results!

Washed foal RBCs with mare serum plus complement

Positive if hemolysis or agglutination

Question 34

What is the treatment for neonatal isoerythrolysis?

When is a whole blood generally indicated?

Answer 34

•Treatment

–IV fluids and whole blood

–Whole blood generally indicated if

•PCV<12%, hyperlactemia (impaired tissue perfusion) persists or foal is lethargic/recumbent without concurrent disease

–Mare RBCs washed three times or if not available cross matched whole blood or blood from Qa and Aa negative donor

Question 35

How do we work out how much blood product to give a foal suffering from neonatal isoerythrolysis?

Answer 35

Question 36

How can we prevent neonatal isoerythrolysis?

Answer 36

–Prevent subsequent foals from nursing for 24-48hrs and provide an alternate source of colostrum

–Blood typing or mare and sire