The long-term epidural administration of morphine in a heavily pregnant mare successfully controlled her pain arising from severe lameness without causing any apparent issues for her foal.
Alessandro Mirra, Jasmin Birras, Sabina Diez Bernal and Claudia Spadavecchia have described their treatment of the 550kg mare in a case report published in the journal BMC Veterinary Research.
The four, in the Department of Clinical Veterinary Medicine at the University of Bern in Switzerland, note that epidural use of morphine has been shown to be an effective painkilling strategy in horses.
However, the risk of side effects, including slowing the gastrointestinal system, limits its use.
“In order to decrease their frequency, it is important to target the minimal effective plasma concentration and avoid overdosing,” they say.
As species-specific pharmacokinetics information is not available for epidural morphine, the dosing regimen is usually established on the basis of clinical reports and personal experience.
In certain physiological conditions, such as pregnancy, the outcome of an empirical dosing scheme can be unpredictable.
The authors, in their paper, describe the pharmacological profile of morphine and its metabolic byproducts after prolonged epidural administration in the pregnant mare and her foal.
The 20-year-old horse was taken to the hospital because of severe lameness. She was still two months short of full term.
Systemic pain treatment did not effectively control her pain, so an epidural catheter was inserted and morphine was given at an initial dose rate of 0.1 milligrams per kilogram of body weight every eight hours.
A previous study had shown that a single dose up to this level does not delay gastrointestinal transit time.
The morphine controlled the pain well and was continued until the end of her pregnancy.
The eight-hourly doses continued uneventfully for more than a fortnight, with careful monitoring of the mare and the foal she was carrying.
After 16 days, the mare entered an excited phase. A morphine overdose was suspected, even though it could not be correlated to any particular injection or time interval after injection.
The dose was switched to epidural methadone. Two days later, once the mare had stabilised, the methadone was stopped and morphine restarted.
On day 21, the morphine interval was reduced to six hours and some ketamine was added.
On day 42, a milder excitatory episode occurred, with methadone substituted for 24 hours, before the morphine was restarted at half the dosage.
On day 49 the foal was delivered and the morphine was reduced further. Four days later, the epidural administration ended and a low dose of morphine and ketamine was given every eight hours by injection into the muscle.
On day 57, the mare and foal left the hospital, with painkilling therapy continued at home by a private veterinarian.
Plasma concentrations of morphine and its byproducts were assessed in the mare six weeks after starting the treatment, and in both the mare and foal during the first days after delivery.
Plasma values in the mare were similar to those previously reported after short-term administration of morphine through various routes at levels not accompanied by side effects.
Mild reduction of feces production with no signs of colic was noted in the mare, and she also had the two self-limiting episodes of excitement during treatment.
No evidence of dangerous drug accumulation or significant milk passage was found in the foal.
“No side effects occurred during gestation and first phases of life in the foal,” they report.
“Prolonged epidural administration of morphine in a pregnant mare allowed good pain control in absence of clinically relevant side effects, in both the mare and her foal,” the four concluded.
However, they added that a sudden increase in morphine concentration in the plasma can occur, with side effects appearing.
“Careful treatment to the lowest effective dose and continuous monitoring of the clinical condition of the treated horse should be performed.”
Their case report also detailed plasma concentrations of morphine and its metabolites after long-term treatment.
“Results show that plasmatic level reached over prolonged epidural administration do not exceed those previously reported to be effective and at the same time safe for the animal.”
Mirra, A., Birras, J., Diez Bernal, S. et al. Morphine plasmatic concentration in a pregnant mare and its foal after long term epidural administration. BMC Vet Res 16, 19 (2020). https://doi.org/10.1186/s12917-020-2242-9