Equine Neonatology Flashcards
What is the normal foetal heart rate at various stages in gestation?
Early rates can be as high as 135 +/-6
By 120 days this should decrease to ~90bpm
By 330 days this should decrease to ~60-80
What treatments may be useful for increasing foetal oxygen delivery in-utero?
- Pentoxyfylline - has anti-inflammatory effects as well as rheologic effects that may enhance O2 delivery by improving microcirculation.
- Intra-nasal O2 insufflation to the mare at 10-15L/min will increase the partial pressure of O2 and O2 saturation in the arterial blood so may improve O2 deliver to the foetus.
- Vitamin E has been used in management of high risk pregnancies as an antioxidant.
What is the first step in activation HPA axis in the foetus for neonatal life?
Foetal cortisol begins to rise approximately 5 days before birth and prepares the foal for extra-uterine life/processes including respiration, renal sodium conservation and glucose metabolism. Cortisol continues to rise in the first few hours after birth before decreasing to normal values by 1 day of age in healthy foals.
What role do neurosteroids play in the peri-partum period?
High circulating concentrations of neurosteroids, in particular allopregnanolone and pregnanolone play a role in maintaining the foal in a sleepy state in utero (along with other factors). These inhibitory neurosteroids are synthesised from progesterone primarily within the placenta during late gestation and act on the cerebrum. Following delivery their concentrations in normal neonates decline rapidly, usually over the first 48 hours of life and it is this loss of cerebral inhibition, in combination with the stimulation associated with transiting the birth canal, onset of breathing and onset of multiple external stimuli that leads to the rapid increase in activity and awareness in the neonate.
What heart rate and respiratory rates do you expect in the neonate and how do these change over the first days of life?
Respiration: 50-75 rpm for first 20-30 min, decreasing to 30-40 rpm for the first 2 days of life then decreasing to ~20 rpm by 2-3 days of age.
Heart rate: 60-80 bpm for the first 40-60 min, increasing to 120-150 bpm by 1-2 hours and stabilising at 100-120 bpm by 3 hours after birth. This usually decreases to 80-100 bpm by 1 day of age.
Within what time frame should a “normal” foal nurse?
Within 3 hours.
What mechanisms are involved in intestinal absorption of macromolecules in colostrum?
Pinocytosis, lymphatic transport and exocytosis.
What variables affect the duration of gestation in mares?
- Breed (light breeds typically shorter than heavy breeds)
- Foetal gender
- Foetal weight
- Maternal age/parity
- Placental functionality (eg mares with lots of cysts have a smaller placental area for transfer of nutrients so may have an increased gestation length)
- Environmental factors (month of conception, maternal nutrition, climate)
What are common findings (physiologic rather than appearance) in dysmature foals?
Impaired thermoregulation
- Abnormal glucose metabolism/regulation (endocrine dysfunction, possibly due to impaired insulin production or peripheral insulin insensitivity)
- Impaired cardiovascular function (most commonly persistant hypotension poorly responsive to pressor therapy. Increased vascular permeability may also be present).
- Impaired pulmonary function (can be surfactant dysfunction, most commonly is associated with decreased respiratory drive, weak muscles of respiration, a highly compliant chest wall and poorly compliant lungs).
- Impaired gastrointestinal function
- Impaired renal function (may manifest primarily as decreased urine output rather than azotaemia - fluid overload is a risk)
What are the goals or targets of treating hypotension in foals?
Fluid therapy, ionotropes and pressor support should target maintenance of perfusion rather than a specific blood pressure range due to the risk of fluid overload.
What is the normal neutrophil:lymphocyte ratio and what do aberrations in this ratio suggest?
Normal N:L ratio is >2.0. Reversal of this ratio (such as ratio of <1.0 suggests prematurity and is directly due to impaired adrenocortical function. Maturation of the HPA axis normally occurs in the last few days of gestation and continues in the first weeks and even months after birth; hence premature foals exhibit low cortisol concentrations at birth, in combination with elevated ACTH.
What are typical features of post-mature foals?
- Normal-high birth weight
- Large frame size but poor body condition
- Long silky haircoat
- Fully erupted incisors
May have flexor contracture.
May share functional characteristics with premature foals such as impaired thermoregulation, abnormal glucose metabolism, impaired GIT and renal function etc.
What are the most common conditions that are associated with a need to resuscitate?
Post-partum (absence of breathing, irregular gasps, RR <10rpm); primary lung disease, septic shock, hypovolaemia, metabolic acidosis, hyperkalaemia, hypoglycaemia, vasovagal reflex and hypothermia. Cardiac causes include secondary myocardial damage from hypoxia or stress, myocarditis, congenital cardiac defects, endocarditis with coronary artery embolism and cardiac tamponade.
What rate and volume of ventilation should be provided during resuscitation of foals?
Tidal volume of 10mL/kg
Rate of 10 breaths per minute. Excessive ventilation will limit cardiac return and coronary perfusion and is associated with worse outcomes.
What would be a benefit of ventilating a foal with 100% O2 briefly immediately after delivery?
May assist with reversal of foetal circulation. Prolonged use is contraindicated unless underlying respiratory dysfunction is noted.
Describe the process of cardiopulmonary resuscitation including frequency of checks and cut-offs for intervention.
- Start with pulmonary support as pulmonary arrest followed by cardiac arrest is a more common scenario.
- Following 30 seconds of ventilation stop and observe for spontaneous breathing while assessing cardiovascular function. If HR >50bpm but respiration is not, resume ventilation but stop every 2 min to check for spontaneous efforts. If heat beat is absent or rate is too low then immediately initiate thoracic compressions (check for rib fractures first!)
- Cardiac compressions are applied at 100bpm, stopping every 2-3 min to check for a heart beat, but resume within 10 seconds if not detected.
- First line medication is adrenaline either IV at 0.01mg/kg every 3-5 min or intra-tracheally at 0.1mg/kg diluted in 3-5mL sterile water. Vasopressin can be used adjunctively at a single dose of 0.6U/kg IV followiing the first dose of adrenaline.
- Doxapram is contraindicated as it doesn’t reverse secondary apnoea and decreases cerebral blood flow while increasing cerebral oxygen consumption
- Atropine and glycopyrrolate are not indicated as high vagal tone is not the cause of bradycardia although a single dose of atropine is unlikely to be harmful.
- Corticosteroids, calcium gluconate, lignocaine, MgSO4 and NaHCO3 are not indicated unless it is primary cardiac arrest due to cardiac disease.
What charge should be applied with defibrillation and in what specific cases?
Cases of ventricular fibrillation and pulseless ventricular tachycardia.
Initially 2J/kg then increasing to 4J/kg for subsequent attempts
What monitoring techniques are useful in resuscitation?
ECG can be misleading as electrical activity doesn’t necessarily represent contractility.
EtCO2 is useful if capnography is available - a normal resting EtCO2 in a healthy patient is 35-45mmHg. During resuscitation a reasonable target is 10mmHg.
Define SIRS and its consequences
A common terminal phase of the inflammatory response characterised by malignant global activation of multiple proinflammatory pathways. SIRS can lead to shock which is characterised by severe hypotension (not responsive to IVFT) which can then result in hypoperfusion and organ dysfunction such that homeostasis cannot be maintained without intervention - this process is termed multiple organ dysfunction (MODS). Typically the first system affected is the cardiovascular system followed by involvement of respiratory, hepatic, GIT, renal, cardiac and neurologic systems, most likely due to tissue hypoperfusion and changes in cellular metabolism secondary to hypoxia. The result is refractory hypotension, lactic acidosis, oliguria and potentially progression to death.
List mediators and describe their involvement in the progression of SIRS
The inciting cause of SIRS may be associated with trauma or microbial invasion that release damage-associated molecular patterns (DAMPS) or pathogen-associated molecular patterns (PAMPS) respectively (eg endotoxin, exotocin, LPS etc); however the development of an inflammatory response is dependent on the production (primarily by the activated mononuclear phagocyte) of numerous inflammatory mediators (incl. TNF-A, IL1, IL6, inducible NOS, phospholipase A2, COX2, and adhesion molecules. Transcription of many of these mediators is dependent on nuclear factor KB which might be a target for intervention of SIRS. In addition to phagocytosis of foreign material, macrophages at the site of injury release proinflammatory cytokines (IL1, TNFA, IL6, IL12, IL18 which increase production of secondary inflammatory mediators incluidng prostaglandins, thromboxane A2 and leukotrienes and reactive oxygen species. IL6, IL1 and TNFA initiate the acute phase response. Part of this is a counter-regulatory anti-inflammatory component that regulates inflammation and resolved the inflammatory response, including inhibiting macrophage activation, antagonises the receptors of the proinflammatory mediators and maintains a balance between pro and anti-inflammatory. In SIRS this balance is not maintained.
What causes endothelial activation during SIRS and what is the effect of this?
Inflammatory cytokines cause endothelial activation early in the process of SIRS. Activated endothelial cells produce NO, prostaglandins and endothelin 1. Activated endothelial cells retract from one another increasing the size of the intercellular pores and allowing for increased vascular permeability, and also increase their production of tissue factor and von Willebrand factor, resulting in localised thrombosis and platelet adherence. An early systemic effect is pulmonary vasoconstriction leading to pulmonary hypertension followed by systemic hypotension due to decreased arterial tone and decreased left ventricular afterload combined with venous vasodilation in capacitance vessels, reducing venous return to the right heart. This can lead to hyperdynamic shock with tachycardia and increased cardiac output as a compensatory mechanism to maintain tissue perfusion. Arteriolar vasoconstriction develops and in addition you get adherence of neutrophils to the endothelium, endothelial cell swelling and accumulation of fibrin and aggregates of platelets and RBCs that occlude the vasculature and exacerbate tissue hypoperfusion. A-V shunting occurs in some tissues, and increased vascular permeability leads to oedema. These all culminate in the end result leading to MODS.
What factors lead to activation of coagulation and development of DIC?
Primarily via the extrinsic pathway.
Normally accumulation of fibrin (secondary to neutrophil degranulation and associated platelet adhesion) would be prevented by the fibrinolytic system (specifically plasmin). However in the presence of SIRS, the fibrinolytic system is inhibited by plasminogen-activator inhibitory type 1. The combination of impaired fibrinolysis and depression of the inhibitors of coagulation can result in a consumptive coagulopathy potentially leading to DIC.
Is gram positive or gram negative more common as an isolate from blood culture in septic neonates?
Gram negative is more common. In the past decade there has been an increased incidence of gram positive findings, although these are often present in mixed infections.
In addition to sepsis, what are the differentials that should be considered for a sick neonate without localising signs?
- NE
- EHV-1
- EVA
- C. psittaci (usually signs of respiratory dysfunction but not always initially)
- NI
- Aspiration pneumonia? (usually signs localised to respiratory tract)
- Colitis (usually signs of colic or diarrhoea)
List common bacterial isolates from foals with sepsis.
Gram -ve:
E. coli, Klebsiella pneumoniae, Actinobacillus, Enterobacter, Pseudomonas aeruginosa, Citrobacter, Pasteurella, Salmonella, Serratia, Acinetobacter.
Gram +ve: B-haemolytic strep, other strep, Staphylococcus, Clostridia, Enterococcus.
Describe fluid resuscitative techniques for foals.
Initial resusc: 20mL/kg boluses given over 10-30min with assessment of volume status between boluses, up to a maximum of 3 boluses (60mL/kg total).
If hypotension is fluid refractory, use of ionotropes or vasopressors may be indicated.
Fluid for resuscitation should be isotonic balanced replacement solutions such as Hartmann’s.
What are the advantages and disadvantages of placing an indwelling urinary catheter in a recumbent sick foal?
Pro’s: greatly helps nursing care/hygiene, reduces risk of decubital ulcers, enables monitoring/quantification of urinary output.
Con’s: Increased risk of urinary tract infection
What neurologic signs/reflexes are present or absent in neonates?
Menace: develops by 1-2 weeks of life
Dazzle: present from birth
PLR (direct & consensual): present from birth but may be slow
Globe position: may be slightly ventromedial but resolves by 1 month
Cutaneous reflexes: present from birth
Limb reflexes: present from birth
Crossed extensor reflex: present from birth but absent after the first 3 weeks
Describe the pathophysiology of organ dysfunction with hypoxic injury/HIE.
- GIT and renal are typically most susceptible
- Shift towards anaerobic metabolism leads to depletion of ATP, accumulation of lactate and failure of cellular homeostasis.
- Decreased activity of transcellular pumps that rely on ATP leads to intracellular accumulatino f Na, Ca and H2O.
- Membrane depolarisation leads to release of glutamate, accumulating in extracellular spaces. This acts on NMDA receptors, opening NMDA channels and potentiating Ca influx into the neurons, contributing to neuronal injury.
- Hypoxia (and subsequent reperfusion) increases production of ROS and NO causing reperfusion injury/tissue damage and cell death and activation of apoptotic cascades
- The stimulated inflammatory response exacerbates vascular permeability, oedema formation and tissue injury.
- The role of neurosteroids is poorly understood - they may be both protective and damaging.
List differentials for NE.
- HIE
- SAE
- Elevated neurosteroid concentrations?
- Kernicterus?
What factors make neonates more susceptible to seizures?
Relative exciteability of the developing brain
High risk of brain injury in the neonatal period (hypo or hyperglycaemia, electrolyte derangements, hypoxia etc)
List the signs of seizure in neonates
Subtle signs:
abnormal eye movements, tremors, excessive stretching, excessive extensor tone, hyperaesthesia, apneustic breathing.
Overt signs: rapid nystagmus, paddling, hyperextension, excessive mouth movements.
List clinical signs of bacterial meningitis
Lethargy, weakness, recumbency, decreased suckle reflex, abnormal PLR, hyperaesthesia, cervical pain, fever, blindness, seizure and coma.
What are the common bacterial isolates in meningitis and what would be suitable antibiotic choices?
*Typically similar bacteria to those associated with neonatal sepsis.
E. coli, Actinobacillus, Klebsiella, Streptococcus, Salmonella.
Drugs that penetrate the BBB: ceftriaxone, chloramphenicol, rifampicin with TMPS.
What type of botulism is most common in foals?
Toxicoinfectious (spores from the environment are ingested and germinate in the GIT and spread toxin).
How does botulism affect the nervous system?
Toxin acts presynaptically at the neuromuscular junction by inhibiting release of acetycholine, resulting in weakness, trembling, dysphagia and sometimes acute death.
What are the common toxin types in botulism and their associated prognosis?
Type B and C are most commonly associated with equine cases; less commonly A.
Toxin A has been associated with more severe clinical signs and higher fatality rate than type B and C.
What are the signalment characteristics of foals with tetanus and what are the common clinical signs?
Typically over 7 days age; history of anaerobic infection, often of the umbilical remnants.
Tetanospasmin inhibits release GABA by spinal interneurons leading to disinhibition of spinal motor neurons hence excessive motor activity and spastic paralysis. Signs are: rigidity, excessive autonomic activity, episodic muscle spasms leading to trismus, facial spasm, third eyelid prolapse and dysphagia. Recumbency may occur and death is due to respiratory muscle paralysis.
List the common metabolic encephalopathies and their cause.
- Hypoglycaemia: associated with central and peripheral neuronal degeneration - unless insulin therapy is being used this typically results in only transient injury and dysfunction.
- Hypo or hypernatraemia: only if severe; or with acute changes in serum Na concentration that cause dramatic fluid shifts in tissues of the CNS - hyponatraemia is associated with development of cerebral oedema; hypernatraemia may be associated with an osmotic demyelination syndrome. Correction of Na derangements should be done slowly.
- Hypocalcaemia: often asymptomatic but may be associated with tetany and seizures.
- Hyperbilirubinaemia: bilirubin is neurotoxic and can cause neurologic dysfunction and irreversible brain damage (kernicterus)
- Hyperammonaemima: can be secondary to hepatic insufficiency, portosystemic shunts or increased gastrointestinal production.
- Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a genetic defect in the urea cycle resulting in persistent hyperammonemia in Morgan foals.
List typical findings in foals with occipitoatlantoaxial malformation.
- Paresis and ataxia of all 4 limbs or may be born dead or comatose.
- May have a head tilt, abnormal head carriage or clicking sound with head movement.
- Neuro deficits range from inapparent to quadriplegia.
Familial in Arabians. Can occur in other breeds.
What is the mode of inheritance for cerebellar abiotrophy?
Autosomal recessive trait
What specific lineage of Arabians does juvenile idiopathic epilepsy occur in?
Egyptian
What are the mainstay of treatment of NE?
- Stabilise the patient to enable restoration and maintenance of CNS perfusion with O2 and glucose.
- IVFT +/- glucose supplementation +/- vasopressors and ionotropes
- Maintain euvolaemia (overhydration can be equally detrimental to CNS perfusion)
- Intranasal O2 insufflation to support O2 delivery
- Control seizures (if present) with benzodiazepines as boluses or CRIs or with phenobarbital (other medications may also be useful)
- Minimal evidence to support DMSO as an anti-inflammatory but it may be useful.
- Mannitol may be useful for reducing cerebral oedema. Hypertonic has more beneficial effects but its use in foals is often contraindicated due to such high Na concentrations.
- MgSO4 is an NMDA receptor antagonist and may stabilise cell membranes, inhibit free radical production and reduce secondary CNS inflammation and associated injury.
- Pentoxyfylline has anti-inflammatory and immune-modulating effects and may improve local tissue perfusion.
List differentials for acute respiratory distress immediately post partum
- Causes of URT obstruction
- Bilateral choanal atresia
- Stenotic nares
- Laryngeal oedema or collapse
- Dorsal displacement of the soft palate
- Subepiglottic cysts
- Severe congenital pulmonary abnormalities
- Congenital cardiac anomalies such as malpositioning of the great vessels causing severe right-to-left shunts may be involved.
Define acute lung injury (ALI/EqALI) and acute respiratory distress syndrome (ARDS/EqARDS)
Syndromes of respiratory failure associated with non-cardiogenic pulmonary oedema, decreased pulmonary compliance and ventilation perfusion mismatching associated with exaggerated and self-perpetuating inflammatory response which results in severe tissue damage within the lung. Protein rich oedema fluid accumulates within the alveoli and interstitium resulting in impairment of gas exchange causing hypoxaemia. These are not primary diseases, merely secondary effects of another primary disease.
EqARDS: PaO2/FiO2 ratio of <200mmHg
EqALI: PaO2/FiO2 ratio of <300mmHg
What is the expected influence of lateral recumbency on arterial blood oxygenation?
Reduction by 10-14mmHg
List the mechanisms that can cause hypoxaemia in foals?
Hypoventilation V/Q mismatch Impaired diffusion Intrapulmonary or extrapulmonary shunts Decreased concentration of O2 in inspired air
What are the complications of mechanical ventilation in cases of ARDs/ALI?
- Trauma to the URT from intubation
- Increased risk of LRT infection
- Pulmonary barotrauma and volutrauma
- Air leak syndromes (pneumothorax)
- Haemodynamic complications including impaired venous return
- Bronchopulmonary dysplasia.
Which radiographic pattern is expected in cases of ARDS/ALI?
Ranges from diffuse interstitial pattern to a focal or diffuse coalescing alveolar pattern with multiple bronchograms.
List common differentials for ARDS/ALI in foals?
Bacterial pneumonia Fungal pneumonia Viral pneumonia Smoke inhalation Repeated transfusion of blood products
What is a key consideration in the treatment of ARDS/ALI in older foals?
Ensuring that R. equi is covered in the spectrum of activity of selected antimicrobial. Particularly if the tracheal wash showed evidence of gram positive coccobacilli within pulmonary macrophages.
List treatments for foals with ALI/ARDS
- General supportive care including nursing, IVFT, electrolyte derangement correction etc.
- Antimicrobials
- Intranasal oxygen insufflation
- Corticosteroids
- **Bronchodilators are often contraindicated as bronchoconstriction is not a feature and bronchodilation may worsen V/Q mismatch resulting in death; if used, it must be after administration of O2.
What is persistent pulmonary hypertension?
Also known as persistent foetal circulation or reversion to foetal circulation; it is a syndrome characterised by sustained increases in pulmonary vascular resistance, possibly combined with decreased right ventricular function hence you get right to left shunting through the ductus arteriosis and/or foramen ovale. While it can be idiopathic, it may develop secondary to systemic sepsis, hypoxaemia or acidosis.
It should be suspected in any foal exhibiting progressive or refractory hypercapnoeic hypoxaemia, particularly if intranasal O2 supplementation does not result in significant increase in PaO2. Must rule out primary congenital cardiac anomalies.
What are the treatment options for persistent pulmonary hypertension?
If response to intranasal O2 insufflation is insufficient, mechanical ventilation with 100% O2 may be indicated both to address hypoxia and also to stimulate pulmonary vascular relaxation. Following a brief period of hyperoxia it is recommended to taper the O2 concentration to target PaO2 of 60-100mmHg. Inhaled nitric oxide is the only approved pulmonary vasodilator in humans and its use is reported in foals but its impractical in most settings. Sildenafil (phosphodiesterase type 5 inhibitor) may be effective at doses of 0.5-0.25mg/kg PO up to every 4 hours. Pentoxyfylline (non-selective phosphodiesterase inhibitor) may also be useful.
List congenital URT disorders and their treatment.
Wry nose: surgical repair is salvage only; prognosis for athletic function is poor.
Choanal atresia: surgical repair is salvage only; chronic airway narrowing likely prevents athletic function
Subepiglottic cyst: results in persistent palatal displacement. Surgery may be curative. Concern for aspiration pneumonia as a sequelae.
Cleft palate: surgical correction of smaller defects may be possible; likewise conservative management of small defects may be possible
