Veterinary anaesthesia and analgesia · 2026
Use of a thermo-responsive hydrogel bupivacaine formulation to provide epidural analgesia in Beagle dogs.
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Nam Changhoon, Lee Inhyung, Son Won-Gyun
Аннотация
OBJECTIVE: To evaluate pharmacokinetics, epidural distribution, antinociceptive effects and motor blockade of bupivacaine incorporated into a thermo-responsive hydrogel (TRH) after lumbosacral epidural injection in dogs.
STUDY DESIGN: Randomised, blinded, crossover experimental study.
ANIMALS: Five entire male Beagle dogs.
METHODS: Each dog underwent three assessment protocols: pharmacokinetics, magnetic resonance imaging (MRI), and antinociceptive and motor blockade assessment. Within each protocol, dogs received lumbosacral epidural bupivacaine (0.5%; 0.2 mL kg-1) alone and combined with TRH in a randomised crossover design. Treatments were separated by at least 2 weeks and consecutive protocols by at least 4 weeks, giving six general anaesthetic sessions per dog. Plasma bupivacaine concentrations were measured by liquid chromatography-tandem mass spectrometry. Epidural spread and spinal cord compression were assessed by MRI. Antinociceptive blockade was evaluated by mechanical nociceptive threshold with a digital pressure algometer, and motor blockade by a gait scoring system. Paired outcomes were compared using Wilcoxon signed-rank tests. Data are reported as median (interquartile range).
RESULTS: Peak plasma bupivacaine concentrations were lower with bupivacaine-TRH than with bupivacaine alone [117.0 (96.8-126.5) versus 623.0 (422.5-1039.0) ng mL-1; p = 0.031]. MRI showed greater epidural retention and mild spinal cord compression with bupivacaine-TRH, without clinical neurological deficits. Cranial spread reached the thirteenth thoracic vertebra with both treatments, whereas bilateral spread varied among dogs. Antinociceptive blockade lasted longer with bupivacaine-TRH [7.0 (6.5-7.5) versus 4.0 (3.0-4.0) hours; p = 0.031]. Motor blockade was numerically shorter with bupivacaine-TRH [0.25 (0.12-0.75) versus 1.00 (0.75-1.00) hours], but the difference was not statistically significant (p = 0.063).
CONCLUSIONS: TRH-based epidural delivery of bupivacaine was associated with a lower peak plasma bupivacaine concentration, greater epidural retention, prolonged antinociceptive blockade duration, and cranial spread comparable to that of bupivacaine alone. Clinical Relevance Larger studies incorporating comprehensive safety assessments are warranted.
STUDY DESIGN: Randomised, blinded, crossover experimental study.
ANIMALS: Five entire male Beagle dogs.
METHODS: Each dog underwent three assessment protocols: pharmacokinetics, magnetic resonance imaging (MRI), and antinociceptive and motor blockade assessment. Within each protocol, dogs received lumbosacral epidural bupivacaine (0.5%; 0.2 mL kg-1) alone and combined with TRH in a randomised crossover design. Treatments were separated by at least 2 weeks and consecutive protocols by at least 4 weeks, giving six general anaesthetic sessions per dog. Plasma bupivacaine concentrations were measured by liquid chromatography-tandem mass spectrometry. Epidural spread and spinal cord compression were assessed by MRI. Antinociceptive blockade was evaluated by mechanical nociceptive threshold with a digital pressure algometer, and motor blockade by a gait scoring system. Paired outcomes were compared using Wilcoxon signed-rank tests. Data are reported as median (interquartile range).
RESULTS: Peak plasma bupivacaine concentrations were lower with bupivacaine-TRH than with bupivacaine alone [117.0 (96.8-126.5) versus 623.0 (422.5-1039.0) ng mL-1; p = 0.031]. MRI showed greater epidural retention and mild spinal cord compression with bupivacaine-TRH, without clinical neurological deficits. Cranial spread reached the thirteenth thoracic vertebra with both treatments, whereas bilateral spread varied among dogs. Antinociceptive blockade lasted longer with bupivacaine-TRH [7.0 (6.5-7.5) versus 4.0 (3.0-4.0) hours; p = 0.031]. Motor blockade was numerically shorter with bupivacaine-TRH [0.25 (0.12-0.75) versus 1.00 (0.75-1.00) hours], but the difference was not statistically significant (p = 0.063).
CONCLUSIONS: TRH-based epidural delivery of bupivacaine was associated with a lower peak plasma bupivacaine concentration, greater epidural retention, prolonged antinociceptive blockade duration, and cranial spread comparable to that of bupivacaine alone. Clinical Relevance Larger studies incorporating comprehensive safety assessments are warranted.