Inhibition of heparin precipitation, bacterial growth, and fungal growth with a combined isopropanol-ethanol locking solution for vascular access devices.
BACKGROUND
Clinical reports of ethanol-lock use for the prevention of catheter-related bloodstream infections have been marked by the occurrence of serious catheter occlusions, particularly among children with mediports. We hypothesized that precipitate forms when ethanol mixes with heparin at the concentrations relevant for vascular access devices, but that the use of a combination of two alcohols, ethanol and isopropanol, would diminish heparin-related precipitation, while retaining anti-bacterial and anti-fungal effects.


METHODS
Heparin (0-100units/mL) was incubated in ethanol-water solutions (30%-70% vol/vol) or in an aqueous solution containing equal parts (35% and 35% vol/vol) of isopropanol and ethanol. Precipitation at temperatures from 4 to 40°C was measured in nephelometric turbidity units using a benchtop turbidimeter. Growth of Escherichia coli, Staphylococcus aureus, and Candida albicans colonies were measured following exposure to solutions of ethanol or isopropanol-ethanol. Groupwise comparisons were performed using analysis of variance with Bonferroni-corrected, post-hoc T-testing.


RESULTS
Seventy percent ethanol and heparin exhibit dose-dependent precipitation that is pronounced and significant at the concentrations typically used in mediports (p<0.05). Precipitate is significantly reduced by use of a combined 35% isopropanol-35% ethanol solution rather than 70% ethanol (p<0.05), while maintaining the solution's anti-bacterial and anti-fungal properties. On the other hand, although ethanol solutions under 70% form less precipitate with heparin, such concentrations are also less effective at bacterial colony inhibition than solutions of either 70% ethanol or 35% isopropanol-35% ethanol (p<0.05).


CONCLUSIONS
A combined 35% isopropanol-35% ethanol locking solution inhibits bacterial and fungal growth similarly to 70% ethanol, but results in less precipitate than 70% ethanol when exposed to heparin. Further study of a combined isopropanol-ethanol locking solution for the prevention of catheter-related bloodstream infections should focus on the determination as to whether such a locking solution may reduce the rate of precipitation-related catheter occlusion, and whether it may be administered with low systemic toxicity.
Department of Surgery, Division of Pediatric Surgery, The University of South Florida Morsani College of Medicine, Tampa, FL, USA.
Daniel
D
Restrepo
Department of Surgery, Division of Pediatric Surgery, The University of South Florida Morsani College of Medicine, Tampa, FL, USA.
Nicholas S
NS
Laconi
Department of Chemical & Biomedical Engineering, The University of South Florida, Tampa, FL, USA.
Norma A
NA
Alcantar
Florida Center of Excellence for Drug Discovery and Innovation (CDDI), The University of South Florida, Tampa, FL, USA.
Leigh A
LA
West
Department of Chemical & Biomedical Engineering, The University of South Florida, Tampa, FL, USA.
Audrey L
AL
Buttice
Department of Pharmacy, Tampa General Hospital, Tampa, FL, USA.
Saumil
S
Patel
Department of Surgery, Division of Pediatric Surgery, The University of South Florida Morsani College of Medicine, Tampa, FL, USA; Department of Surgery, Goryeb Children's Hospital, Morristown, NJ, USA. Electronic address: mark.kayton@atlantichealth.org.
Mark L
ML
Kayton
D019840:2-Propanol / Q000737:chemistry* / Q000494:pharmacology; D002176:Candida albicans / Q000254:growth & development; D055499:Catheter-Related Infections / Q000382:microbiology / Q000517:prevention & control; D002648:Child; D004926:Escherichia coli / Q000254:growth & development; D000431:Ethanol / Q000737:chemistry* / Q000494:pharmacology; D006493:Heparin / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D013211:Staphylococcus aureus / Q000254:growth & development; D013696:Temperature; D062666:Vascular Access Devices
D000431:Ethanol; D006493:Heparin; D019840:2-Propanol
Broviac; Catheter related bloodstream infection; Ethanol; Ethanol-lock; Isopropanol; Mediport; Port-a-cath