Effects of regional limb perfusion volume on concentrations of amikacin sulfate in synovial and interstitial fluid samples from anesthetized horses

Abstract

OBJECTIVE To evaluate the effect of volume of IV regional limb perfusion (IVRLP) on amikacin concentrations in synovial and interstitial fluid of horses. ANIMALS 8 healthy adult horses. PROCEDURES Each forelimb was randomly assigned to receive IVRLP with 4 mL of amikacin sulfate solution (250 mg/mL) plus 56 mL (total volume, 60 mL) or 6 mL (total volume, 10 mL) of lactated Ringer solution. Horses were anesthetized, and baseline synovial and interstitial fluid samples were collected. A tourniquet was placed, and the assigned treatment was administered via the lateral palmar digital vein. Venous blood pressure in the distal portion of the limb was recorded. Additional synovial fluid samples were collected 30 minutes (just before tourniquet removal) and 24 hours after IVRLP began; additional interstitial fluid samples were collected 6 and 24 hours after IVRLP began. RESULTS 30 minutes after IVRLP began, mean amikacin concentration in synovial fluid was significantly greater for the large-volume (459 μg/mL) versus small-volume (70 μg/mL) treatment. Six hours after IVRLP, mean concentration in interstitial fluid was greater for the large-volume (723 μg/mL) versus small-volume (21 μg/mL) treatment. Peak venous blood pressure after large-volume IVRLP was significantly higher than after small-volume IVRLP, with no difference between treatments in time required for pressure to return to baseline. CONCLUSIONS AND CLINICAL RELEVANCE Study findings suggested that large-volume IVRLP would deliver more amikacin to metacarpophalangeal joints of horses than would small-volume IVRLP, without a clinically relevant effect on local venous blood pressure, potentially increasing treatment efficacy.

Pharmacokinetics of ceftazidime after regional limb perfusion in standing horses

“…Amikacin is the most commonly used antimicrobial for RLP in horses, and as such, the most studied drug. [5][6][7][8][9][10][11][12][13] As an aminoglycoside, amikacin has a…”

Synovial butorphanol concentrations and mechanical nociceptive thresholds after intravenous regional limb perfusion in standing sedated horses

“…The synovial concentrations achieved in the present study were highly variable, and it is unknown whether the concentrations achieved would be clinically relevant. This variability is a common finding in IVRLP studies . It has been speculated that this occurs because of inherent anatomical or physiological differences between horses, varying efficacy of the procedure, or sample collection issues .…”

“…The half‐life of butorphanol after subcutaneous administration has been reported to be longer than that after IV administration . The degree of extravascular diffusion during IVRLP may lead to subcutaneous retention, thereby sustaining concentrations in the treated region . This is likely underestimated in studies in which the focus is solely on synovial fluid analyses, although it may further advantage IVRLP over systemic or intra‐articular use in horses with distal limb surgery or injury.…”

“…Little consensus exists regarding how IVRLP should be performed, which limits direct comparisons between studies and the ability to identify sources of variability. There is debate concerning the ideal technical aspects of the procedure (eg, tourniquet type and number, perfusate volume, perfusion time), and the available data are equivocal . The IVRLP performed here was intended to reproduce that easily performed by the general practitioner, and attempts were made to ensure consistency of the procedure and sample collection.…”

“…22 The degree of extravascular diffusion during IVRLP may lead to subcutaneous retention, thereby sustaining concentrations in the treated region. 33 This is likely underestimated in studies in which the focus is solely on synovial fluid analyses, although it may further advantage IVRLP over systemic or intra-articular use in horses with distal limb surgery or injury. Measurement of the concentrations achieved in the soft tissues of the limb after butorphanol IVRLP is warranted.…”