A Thoroughbred X Australian Stock Horse colt presented to the Veterinary Clinical Centre (VCC), Charles Sturt University at 5hrs of age. Parturition was not witnessed and the colt was found recumbent in the paddock, unable to stand. The foal had not nursed. The mare is multiparous and had a history of placentitis diagnosed by the referring veterinarian. This had been treated with systemic antimicrobials (trimethoprim sulphonamide) for approximately 2 months prior to foaling. The mare had run milk for 7 days prior to foaling.
On presentation to the VCC, the foal was quiet but alert and responsive. A strong suck reflex was present and occasional attempts to stand were made. Cardinal signs recorded were within normal ranges with the exception of mild hypothermia (36.4°C). Initial haematological and blood biochemical examination revealed a mild leukopenia and neutropenia and hypoproteinemia. There was also a moderate hypercreatinaemia, however this resolved quickly over the first 48hrs of hospitalisation and was therefore most likely associated with placental insufficiency. Other results were not supportive of renal dysfunction and the colt was producing urine with an appropriate USG.
A blood sample was collected aseptically at the time of admission to hospital for blood culture and results revealed a heavy pure growth of Acinetobacter sp. (aerobic Gram-negative bacilli). The sensitivity of the organism was used to direct systemic antimicrobial therapy. Intensive medical management of this colt included replacement intravenous fluid therapy with an initial bolus of Hartmann’s solution, followed by maintenance constant rate infusion (CRI) of polyionic crystalloid fluid (Plasmalyte 56 + 5% glucose). A separate glucose CRI was also commenced with regular monitoring of plasma glucose concentration. Other treatment included nasal oxygen insufflation and an indwelling nasogastric tube was placed to facilitate enteral assisted nutrition, initially with colostrum and then mare’s milk. The volume of each feed was started at 5% body weight/day as 2hrly feeds and gradually increased with close monitoring for signs of abdominal discomfort and/or diarrhoea.
IgG concentration measurement confirmed failure of passive transfer of maternal antibodies and 1L hyperimmune plasma was administered. Repeat IgG concentration measurement was >8g/L. 24 hours after admission, the foal’s mentation and clinical condition deteriorated despite intensive care. He was obtunded with minimal response to stimulation and short intermittent episodes of seizure activity were noted. This included stretching out of the head and neck, paddling with the forelimbs and bilateral nystagmus. This was initially managed with bolus doses of diazepam (0.1mg/kg) administered intravenously. The episodes increased in frequency despite this treatment and a total of 3 doses of diazepam were administered. A decision was made to commence treatment for refractory seizures with a midazolam CRI. A bolus (0.04 mg/kg IV) was administered initially, followed by a CRI, starting at 0.02 mg/kg/hr and gradually increased to 0.06 mg/kg/hr over the following 12 hours due to persistent intermittent seizure activity. A dobutamine infusion was also commenced due to persistent hypotension and there was good response to this.
There was very good response to treatment with midazolam in this case and seizure activity resolved. The infusion rate was gradually decreased and discontinued approximately 60 hours after it was commenced. The dobutamine infusion was also discontinued. There was ongoing improvement in the foal’s mention and clinical condition overall and it was eventually able to stand with assistance. Intravenous fluid therapy was gradually discontinued as the foal was tolerating increasing volumes of mare’s milk via the nasogastric tube. The foal was intermittently assisted to nurse from the mare and was eventually able to nurse without assistance. Serial haematological and blood biochemical examinations confirmed resolution of systemic inflammation and antimicrobial therapy was discontinued. The mare and foal were discharged from hospital 16 days after admission.
It is assumed the neonatal encephalopathy (NE) and seizure activity developed as a consequence of perinatal asphyxia syndrome (PAS) in this case. Conditions associated with PAS in foals include dystocia, caesarean section, placentitis, premature placental separation (‘red bag’ delivery), severe maternal illness, maternal surgery. Many foals have no known peripartum period of hypoxia. Foals with PAS and NE may appear healthy at birth but develop central nervous system abnormalities from within a few hours of birth to 1-2 days of age.
The midazolam infusion was an effective treatment for the intermittent seizure activity in this case. Diazepam and midazolam are benzodiazepines. The mechanism of action of benzodiazepines is through potentiating the activity of endogenous gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter of the central nervous system. The initial use of diazepam in this case was appropriate as diazepam is used preferentially over other benzodiazepines for the treatment of seizures as there is rapid distribution to the CNS following intravenous administration. Repeated doses may be required to achieve adequate seizure control, however if there is minimal response to treatment, alternative medications should be considered. Midazolam has relatively greater lipid solubility than diazepam, resulting in a more rapid onset of action. It is also approximately 3-4 times more potent than diazepam. The lowest effective dose should be used to avoid hypotension and respiratory depression. A CRI is recommended when there is inadequate response to single bolus doses and/or if more than 2 seizure episodes occur.
This case highlights the clinical efficacy of a midazolam CRI for the management of refractory seizures in equine neonates. No major adverse effects were noted with the use of midazolam in this case. The hypotension was effectively managed with a dobutamine infusion. Although negative haemodynamic and neurologic effects have been reported in human neonates, it is unknown if critically ill equine neonates experience these effects. In humans, the duration of treatment is often longer than that used in equine neonates and this may be associated with an increased risk of adverse effects. The pharmacokinetics of midazolam have not yet been published in equine neonates.
Photographs taken on days 4 and 5 of hospitalisation. The foal was maintained in a sternal support and was regularly turned while recumbent. Constant rate infusions of polyionic crystalloids, glucose, midazolam and dobutamine were administered. The foal also has a nasal oxygen tube and indwelling nasogastric tube in place.
Photograph taken on Day 16, prior to discharge from hospital.
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