Concurrent intravenous regional limb perfusion and systemic amikacin administration achieves variable synovial fluid amikacin concentrations in healthy neonatal foals.

Overview

• This study investigated the levels of amikacin, an antibiotic, in the blood plasma and joint fluid of healthy newborn foals after receiving the drug both systemically (throughout the body) and locally through a specific limb perfusion technique.
• The research aimed to determine whether this combined administration method could achieve effective therapeutic drug levels in both the bloodstream and joints to help treat infections.

Background and Purpose

• Amikacin is an antibiotic used to treat bacterial infections, including in joints (septic arthritis) and systemic infections.
• Intravenous regional limb perfusion (IVRLP) is a technique used to deliver high concentrations of antibiotics directly to a limb by restricting blood flow temporarily using a tourniquet.
• The study tested a dosing protocol where a total dose of 25 mg/kg was split into two parts: 16.7 mg/kg given systemically via intravenous injection and 8.3 mg/kg given locally via IVRLP either in the cephalic (front limb) or saphenous vein (hind limb).
• The main hypothesis was that plasma levels of amikacin at 30 minutes after systemic administration would exceed 53 μg/mL (considered therapeutic) and synovial fluid levels would exceed 80 μg/mL.

Study Design and Methodology

• Conducted over a 5-month period in spring/summer 2023, involving 8 healthy newborn foals.
• Each foal received both dosing protocols (cephalic and saphenous IVRLP) at least 48 hours apart to allow for washout and avoid carry-over effects.
• Synovial fluid samples from joints were collected 30 minutes after IVRLP administration to assess local drug concentration.
• The systemic amikacin dose was given at the time of tourniquet release (30 minutes into the regional perfusion), and plasma drug concentrations were measured over a 24-hour period following this administration.

Key Findings

• There was no significant difference in the synovial fluid or plasma amikacin concentrations between the two IVRLP administration sites (cephalic versus saphenous).
• The combined data provided a single estimate of drug concentration for each sample type and time point.
• At 30 minutes post-IVRLP, the mean concentration of amikacin in synovial fluid was 238.5 μg/mL (with a 95% confidence interval ranging from 146.1 to 330.9), well above the therapeutic target of 80 μg/mL.
• At 30 minutes after systemic administration, plasma amikacin concentration averaged 66.3 μg/mL (95% CI, 57.5 to 75.1), exceeding the target of 53 μg/mL.
• Despite the overall positive results, some foals did not reach the desired therapeutic concentration in synovial fluid in all joints sampled, indicating variability in local drug distribution.

Implications and Conclusions

• The study confirms that simultaneously administering amikacin systemically and locally via IVRLP in neonatal foals can achieve effective antibiotic concentrations in both the bloodstream and joint fluid.
• Given that adequate drug levels were observed, this combined treatment approach can be clinically effective for managing systemic infections and concurrent septic arthritis in newborn foals.
• The variability seen in synovial fluid concentrations suggests that individual differences or joint-specific factors may influence drug penetration and should be considered in clinical practice.
• These findings support the use of this dosing protocol to optimize antibiotic therapy in neonatal foals facing complex infections, potentially improving treatment outcomes.