Abstract
ObjectiveThe ethanol lock technique has shown great potential to eradicate organisms in biofilms and to treat or prevent central venous catheter related infections. Following instillation of ethanol lock solution, however, the inherent density gradient between blood and ethanol causes gravity induced seepage of ethanol out of the catheter and blood influx into the catheter. Plasma proteins so are exposed to highly concentrated ethanol, which is a classic agent for protein precipitation. We aimed to investigate the precipitating effect of ethanol locks on plasma proteins as a possible cause for reported catheter occlusions.MethodsPlasma samples were exposed in-vitro to ethanol (concentrations ranging from 7 to 70 v/v%) and heparin lock solutions. In catheter studies designed to mimic different in-vivo situations, the catheter tip was placed in a plasma reservoir and the material contained within the catheter was analyzed after ethanol lock instillation. The samples underwent standardized investigation for protein precipitation.ResultsProtein precipitation was observed in plasma samples containing ethanol solutions above a concentration of 28%, as well as in material retrieved from vertically positioned femoral catheters and jugular (subclavian) catheters simulating recumbent or head down tilt body positions. Precipitates could not be re-dissolved by dilution with plasma, urokinase or alteplase. Plasma samples containing heparin lock solutions showed no signs of precipitation.ConclusionsOur in-vitro results demonstrate that ethanol locks may be associated with plasma protein precipitation in central venous catheters. This phenomenon could be related to occlusion of vascular access devices locked with ethanol, as has been reported. Concerns should be raised regarding possible complications upon injection or spontaneous gravity induced leakage of such irreversibly precipitated protein particles into the systemic circulation. We suggest limiting the maximum advisable concentration of ethanol to 28 v/v% in catheter lock solutions.
Highlights
Protein precipitation was observed in plasma samples containing ethanol solutions above a concentration of 28%, as well as in material retrieved from vertically positioned femoral catheters and jugular catheters simulating recumbent or head down tilt body positions
Our in-vitro results demonstrate that ethanol locks may be associated with plasma protein precipitation in central venous catheters
[24] Several studies using ethanol locks (ELs) for prevention or treatment of catheter related bloodstream infections (CRBSI) reported either Central venous catheters (CVCs) occlusion or precipitated material as well as clots clearly visible upon line aspiration the underlying mechanisms remained unclear. [25,26,27,28] We recently published similar observations in CVCs used with hypertonic citrate lock solution, a protein precipitating agent. [29,30] For decades, plasma proteins have commonly been purified by precipitating them with organic solvents, mainly ethanol
Summary
Central venous catheters (CVCs) allow life saving interventions by providing reliable venous access for hemodynamic monitoring, fluid and drug administration, hemodialysis, chemotherapy, or total parenteral nutrition in neonate, infant and adult patients. [1,2,3] the long-term use of CVCs is fraught with complications including a high rate of infection and thrombus-related dysfunction or occlusion. [4,5] To mitigate the impact of these complications, anticoagulative, antibiotic or antimicrobial catheter lock solutions have been used prophylactically or therapeutically to maintain the intraluminal patency of CVCs. [6] Ethanol, considered an alternative to heparin lock solution for CVCs, is an antimicrobial agent currently used predominantly in patients with intestinal failure relying on total parenteral nutrition as well as in patients with chronic kidney failure requiring renal replacement therapy. [7,8] In-vitro and in-vivo studies have shown the efficacy of ethanol at varying concentrations (20–74%) to eradicate various planktonic pathogens as well as microbial organisms embedded in the intraluminal biofilm of indwelling CVCs. [9,10,11,12,13] In 2011, the latest guidelines from the Centers for Disease Control and Prevention discussed, but did not recommend ethanol locks (ELs) to prevent intravascular catheter related bloodstream infections (CRBSI), while the American Pediatric Surgical Association concluded that ELs can be administered safely and can effectively reduce the incidence of CRBSI (Grades A/B recommendations). [14,15] Oliveira et al [7] and Wolf et al [16] stated in recently published reviews that the evidence for the effectiveness of EL in CRBSI prevention is robust, they were concerned about adverse thrombotic events, retrospective evidence and the absence of a systematic safety assessment in the studies covered.Instillation of the listed filling volume of lock solutions, such as ELs, into the lumen of a CVC was believed to ‘lock’ the CVC, suggesting that the full injected volume of the locking anticoagulant remained inside the CVC. [24] Several studies using ELs for prevention or treatment of CRBSI reported either CVC occlusion or precipitated material as well as clots clearly visible upon line aspiration the underlying mechanisms remained unclear. [25,26,27,28] We recently published similar observations in CVCs used with hypertonic citrate lock solution, a protein precipitating agent. [29,32] The objective of this in-vitro study was to investigate the conditions for protein precipitation in ethanol locked CVCs. The known interaction of ethanol with human erythrocytes mediates hemolysis. In an experimental setting designed to mimic different in-vivo situations, the material in the catheter was analyzed after EL lock instillation
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