Morphine plasmatic concentration in a pregnant mare and its foal after long term epidural administration

Abstract

Background Epidural administration of morphine has been shown to be an effective analgesic strategy in horses; however, the possible occurrence of side effects limits its usage. In order to decrease their frequency, it is important to target the minimal effective plasma concentration and avoid overdosing. As to date species-specific pharmacokinetics data are not available for epidural morphine, the dosing regimen is usually established on the basis of clinical reports and personal experience. In certain physiological conditions, like gestation, the outcome of an empirical dosing scheme can be unpredictable. The aim of this case report is to describe the pharmacological profile of morphine and its metabolites after prolonged epidural administration in a pregnant mare and her foal. Case presentation A 20 years old pregnant mare was presented to our hospital because of severe lameness, 2 months before delivery. Following an ineffective systemic pain treatment, an epidural catheter was inserted and morphine administered (initial dose 0.1 mg/kg every 8 h). Due to its efficacy in controlling pain, it was continued until end of gestation. Plasmatic concentration of morphine and its metabolites were assessed in the mare 6 weeks after starting the treatment, and in both the mare and foal during the first days after delivery. Plasmatic values similar to those previously reported in the literature following morphine short term administration through various routes and not accompanied by side effects were found in the mare, except during an excitatory period. Moreover, no evidence of dangerous drug accumulation or significant milk passage was noticed in the foal. Mild reduction of feces production with no signs of colic and two self-limiting episodes of excitement occurred during treatment in the mare. No side effects occurred during gestation and first phases of life in the foal. Conclusion 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. Sudden increase in morphine plasmatic concentration can occur and side effects appear; careful treatment to the lowest effective dose and continuous monitoring of the clinical condition of the treated horse should be performed.

A narrative review of caudal epidural anaesthesia and analgesia in horses. Part 1: Safety and efficacy of epidural drugs

“…Thus, sedation is a relatively common CNS side-effect of epidurally administered alpha-2 agonists, opioids and dissociative drugs (Table 1). In contrast, CNS excitation is a rare side-effect and has only infrequently been reported in horses after the epidural administration of large doses tiletamine/zolazepam (Natalini et al 2004a) and the opioids morphine and tramadol (Giorgi et al 2010;Mirra et al 2020).…”

“…The epidural route of administration minimises the risk of such systemic side-effects. However, epidural opioids have still occasionally been reported to cause mild GI symptoms, such as temporarily decreased GI motility, decreased frequency of defaecation or mild reduction of faeces, but without the concurrent occurrence of colic (Freitas et al 2011;Sano et al 2011;Kjaerulff et al 2021;Mirra et al 2020). In addition, one study also reported that horses may experience defaecation difficulties after the caudal epidural administration of lidocaine (Olbrich and Mosing 2003), which probably occurs primarily as a result of the indiscriminate blockade of sensory and motor nerves innervating the anus and rectum.…”

“…2021; Mirra et al . 2020). In addition, one study also reported that horses may experience defaecation difficulties after the caudal epidural administration of lidocaine (Olbrich and Mosing 2003), which probably occurs primarily as a result of the indiscriminate blockade of sensory and motor nerves innervating the anus and rectum.…”

Caudal epidural catheterization for pain management in 48 hospitalized horses: A descriptive study of demographics, complications, and outcomes

“…The placement of epidural catheters for continuous caudal epidural therapy in horses was first reported in 1983 and has become more frequently implemented clinically to employ multi-modal analgesic therapies ( 3 , 14 , 17 – 24 ). Caudal epidural catheters have been placed for continuous anesthesia and analgesia for surgical procedures as well as for pain management for orthopedic, rectal, and urogenital conditions ( 3 , 14 , 18 , 19 , 21 , 25 ). Continuous or repeated epidural administration of analgesics offers the advantages of effective analgesia with reportedly fewer side effects than systemic analgesics ( 26 , 27 ).…”

“…Continuous or repeated epidural administration of analgesics offers the advantages of effective analgesia with reportedly fewer side effects than systemic analgesics ( 26 , 27 ). Despite its more frequent application in experimental and clinical settings, there are limited reports on the use of caudal epidural catheterization for long-term administration of epidural analgesics ( 18 , 21 , 24 , 25 ). In an experimental, prospective study on ten horses, no catheter-related complications, such as dislocation, catheter obstruction, leakage, or discomfort during injection were observed during a 14-day experimental observation period ( 24 ).…”