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PloS one2022; 17(4); e0265971; doi: 10.1371/journal.pone.0265971

Effects of regional limb perfusion technique on concentrations of antibiotic achieved at the target site: A meta-analysis.

Abstract: Intravenous regional limb perfusions (RLP) are widely used in equine medicine to treat distal limb infections, including synovial sepsis. RLPs are generally deemed successful if the peak antibiotic concentration (Cmax) in the sampled synovial structure is at least 8-10 times the minimum inhibitory concentration (MIC) for the bacteria of interest. Despite extensive experimentation and widespread clinical use, the optimal technique for performing a successful perfusion remains unclear. The objective of this meta-analysis was to examine the effect of technique on synovial concentrations of antibiotic and to assess under which conditions Cmax:MIC ≥ 10. A literature search including the terms "horse", "equine", and "regional limb perfusion" between 1990 and 2021 was performed. Cmax (μg/ml) and measures of dispersion were extracted from studies and Cmax:MIC was calculated for sensitive and resistant bacteria. Variables included in the analysis included synovial structure sampled, antibiotic dose, tourniquet location, tourniquet duration, general anesthesia versus standing sedation, perfusate volume, tourniquet type, and the concurrent use of local analgesia. Mixed effects meta-regression was performed, and variables significantly associated with the outcome on univariable analysis were added to a multivariable meta-regression model in a step-wise manner. Sensitivity analyses were performed to assess the robustness of our findings. Thirty-six studies with 123 arms (permutations of dose, route, location and timing) were included. Cmax:MIC ranged from 1 to 348 for sensitive bacteria and 0.25 to 87 for resistant bacteria, with mean (SD) time to peak concentration (Tmax) of 29.0 (8.8) minutes. Meta-analyses generated summary values (θ) of 42.8 x MIC and 10.7 x MIC for susceptible and resistant bacteria, respectively, though because of high heterogeneity among studies (I2 = 98.8), these summary variables were not considered reliable. Meta-regression showed that the only variables for which there were statistically significant differences in outcome were the type of tourniquet and the concurrent use of local analgesia: perfusions performed with a wide rubber tourniquet and perfusions performed with the addition of local analgesia achieved significantly greater concentrations of antibiotic. The majority of arms achieved Cmax:MIC ≥ 10 for sensitive bacteria but not resistant bacteria. Our results suggest that wide rubber tourniquets and concurrent local analgesia should be strongly considered for use in RLP and that adequate therapeutic concentrations (Cmax:MIC ≥ 10) are often achieved across a variety of techniques for susceptible but not resistant pathogens.
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Publication Date: 2022-04-01 PubMed ID: 35363825PubMed Central: PMC8974993DOI: 10.1371/journal.pone.0265971Google Scholar: Lookup
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  • Journal Article
  • Meta-Analysis

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research study used a meta-analysis methodology to investigate the effectiveness of different techniques for intravenous regional limb perfusions (RLP) —a treatment commonly used in equine medicine for distal limb infections—to achieve optimal antibiotic concentrations at the infected site. The study found that using a wide rubber tourniquet and integrating local analgesia during perfusion resulted in significantly higher antibiotic concentrations.

Methodology

  • The study performed a literature review covering the last three decades (1990-2021), focusing on the terms “horse”, “equine”, and “regional limb perfusion”.
  • Data about the peak antibiotic concentration (Cmax) in the affected synovial structure and its ratio to the minimum inhibitory concentration (MIC) for bacteria were extracted from the selected studies.
  • The researchers assessed multiple variables such as sampled synovial structure, antibiotic dosage, location and duration of tourniquet, administration of anesthesia, volume of perfusate, type of tourniquet, and the simultaneous use of local analgesia.
  • Statistical analyses, including mixed effects meta-regression and multivariable meta-regression were conducted to examine the effect of each variable on the study outcome.
  • The analysis included findings from 36 studies with 123 arms (combinations of different variables).

Results

  • The mean time to reach peak antibiotic concentration was approximately 29 minutes.
  • For sensitive bacteria, the ratio of Cmax to MIC (Cmax:MIC) varied considerably, ranging between 1 to 348.
  • For resistant bacteria, this ratio was significantly lower, ranging from 0.25 to 87.
  • Despite the heterogeneity among the studies, the meta-analysis found on average that Cmax was 42.8 times the MIC for the sensitive bacteria and 10.7 times that for the resistant bacteria.
  • The type of tourniquet used and the administration of local analgesia were the only two variables significantly affecting the outcome of RLPS. Specifically, the use of a wide rubber tourniquet and concurrent local analgesia resulted in higher antibiotic concentrations.

Conclusions

  • The study conducted a thorough investigation of the impact of different techniques on the antibiotic concentrations achieved in regional limb perfusions (RLP)
  • Despite the high variation among studies, the research provided some insightful suggestions on the possible optimizations of RLP techniques.
  • Specifically, a wide rubber tourniquet and the inclusion of local analgesia should be considered to reach adequate antibiotic concentrations, especially for combating sensitive bacteria. However, they may not be as effective against resistant bacteria.

Cite This Article

APA
Redding LE, Elzer EJ, Ortved KF. (2022). Effects of regional limb perfusion technique on concentrations of antibiotic achieved at the target site: A meta-analysis. PLoS One, 17(4), e0265971. https://doi.org/10.1371/journal.pone.0265971

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 17
Issue: 4
Pages: e0265971
PII: e0265971

Researcher Affiliations

Redding, Laurel E
  • Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania.
Elzer, Elizabeth J
  • Rood and Riddle Equine Hospital, Saratoga Springs, New York, United States of America.
Ortved, Kyla F
  • Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania.

MeSH Terms

  • Amikacin
  • Animals
  • Anti-Bacterial Agents
  • Forelimb
  • Horses
  • Perfusion
  • Rubber
  • Synovial Fluid / chemistry

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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Citations

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