Cover Story | Orthopedics

Limb Wounds Can Kill Careers

By Marie Rosenthal MS

Higher levels of synovial amikacin can be found after IV regional limb perfusion if the perfusate is given at a slower rate, according to a recent study by Laurel K. Saldinger, DVM, and her colleagues at the University of California, Davis.

“Wounds to the equine limb can have grave consequences with synovial sepsis occurring secondary to distal limb wounds being common,” Dr. Saldinger explained during a presentation at the 70th AAEP Annual Meeting in Orlando, Fla. “This can have a huge impact, especially on our equine athletes.”

Treatment for these wounds typically includes IV regional limb perfusion (IVRLP), usually with amikacin. “Amikacin is one of the most effective antibiotics against bacterial isolates from orthopedic infections in horses, which, along with being a concentration-dependent antibiotic, makes an excellent choice for regional limb perfusions,” said Dr. Saldinger, an equine surgery resident at UC Davis School of Veterinary Medicine. “The target level we want in these tissues is going to be 10 times the MIC [minimum inhibitory concentration] of the bacteria for amikacin.”

To achieve this, Dr. Saldinger recommended an MIC of at least 4 mcg/mL for the most sensitive bacteria, up to approximately 16 mcg/mL for resistant bacteria. The goal should be to get 160 mcg/mL in the tissues or synovial structures of the horse, she said.
Dr. Saldinger, Isabelle Kilcoyne, MVB, DACVS, and Jorge Nieto, MVZ, PhD, DACVS, wanted to know if synovial amikacin concentrations varied depending on the time it took to perfuse the medication.

In this crossover study, the researchers chose 7 horses (4 geldings and 3 mares) that were free of lameness and had no evidence of carpal disease or vascular abnormalities. The breeds included 2 Paints, 1 Quarter Horse and 1 Thoroughbred, 1 Westphalian, 1 Oldenburg and 1 Hanoverian. The median age of these horses was 13 years, with a range from 5 to 18, and the median weight was 560 kg.

During the first part of the experiment, the investigators randomly chose a leg and administered IVRLP with the perfusate given over 1 minute or 5 minutes. After a 3-week washout period, the horses then received IVRLP of another limb with the opposite perfusate installation time. So, if the horse received the perfusate during 1 minute at the first administration of perfusate, then the second perfusate was given over 5 minutes. The same investigator performed each perfusion.

The perfusions of 2 g of amikacin, which were diluted to a volume of 60 mL with saline, were given to patients that were sedated and had received a nerve block to reduce sensation to the limb. A wide rubber tourniquet was placed above the carpus at the proximal aspect, which allowed them to separate the distal limb from the systemic circulation.

“So, with a 60-mL total volume, we were aiming to either give the perfusate at a rate of 1 mL per 1 second or 1 mL per 5 seconds. The tourniquet was then left in place for 30 minutes,” she explained. “During this time, increased hydrostatic pressure will allow for improved antibiotic perfusion into our tissues and synovial structures.”

They took synovial fluid samples every 5 minutes, beginning at the start of the regional limb perfusion and continuing until its conclusion at 30 minutes. Blood was collected every 5 minutes during the regional perfusion and then again 1 minute after the tourniquet was removed. The samples were used to determine the amikacin concentrations.

They found that every horse that received perfusate during the 5-minute perfusion achieved the desired concentration of 160 mcg/mL in the radiocarpal joint, and only 5 of the 7 horses achieved the same level during the 1-minute perfusion.

However, the results were not statistically significant. The median maximum concentration (CMAX) of amikacin in the synovial fluid during the 1-minute delivery was 338 mcg/mL, and the CMAX during the 5-minute perfusion was 694 mcg/mL, Dr. Saldinger said.

“What was significantly different in our study was our systemic concentration of amikacin,” she explained. “There was a higher amikacin blood concentration over time in the 1-minute group as compared with the 5-minute group, and this was significant, with a P value of 0.004.”

The difference in the systemic levels of amikacin suggests there was more leakage when the perfusate was given quickly, she said, which suggests higher synovial levels can be achieved because less drug is lost during the procedure.

“The reduction in systemic values that we saw with slow administration of perfusate is exciting to us, and it will be beneficial in practice. A lowered systemic value will help to reduce drug resistance and improve our ability to use amikacin when we need it for other situations,” Dr. Saldinger said. MeV

For more information:
Saldinger LK, Kilcoyne I, Nieto J. Faster perfusate instillation time results in more systemic leakage of amikacin sulfate when performing intravenous regional limb perfusion in horses. Am J Vet Res. 2024;85(6):ajvr.24.02.0029.
https://avmajournals.avma.org/view/journals/ajvr/85/6/ajvr.24.02.0029.xml