The risk of peripheral vein phlebitis associated with chlorhexidine-coated catheters: a randomized, double-blind trial.

OBJECTIVE: To evaluate the risk of phlebitis associated with chlorhexidine-coated polyurethane catheters in peripheral veins. DESIGN: A randomized, double-blinded trial comparing chlorhexidine-coated polyurethane catheters with uncoated polyurethane catheters. SETTING: A university hospital. PATIENTS: Adult medicine and surgery patients. INTERVENTIONS: Certified registered nurse anesthetists or an infusion team consisting of nurses and physicians inserted the catheters. Catheter insertion sites were scored twice daily for evidence of phlebitis. At the time catheters were removed, a quantitative blood culture was performed, and catheters were sonicated for quantitative culture. RESULTS: Of 221 evaluable catheters, phlebitis developed in 18 (17%) of 105 coated catheters, compared to 27 (23%) of 116 uncoated catheters (relative risk [RR], 0.74; 95% confidence interval [CI95], 0.43-1.26; P = .32). By survival analysis, chlorhexidine-coated catheters had a lower risk of phlebitis during the first 3 days (P = .06), but not when all catheters were considered in both patient groups (P = .31). In the absence of catheter colonization, the incidence of phlebitis was 21% (16/76) and 24% (20/86) for coated and uncoated catheters, respectively (P = .85), whereas in the presence of catheter colonization, the incidence of phlebitis was 14% (1/7) and 80% (4/5) for coated and uncoated catheters, respectively (RR, 0.18; CI95, 0.03-1.15; P = .07). CONCLUSION: The risk of phlebitis in the presence of catheter colonization was 82% lower for chlorhexidine-coated polyurethane catheters compared to otherwise identical uncoated catheters.

Contribution of vascular catheter material to the pathogenesis of infection: the enhanced risk of silicone in vivo.

There is currently very little information to suggest that polymer materials used to make vascular catheters differ in their risk of infection. A rabbit model of subcutaneous Staphylococcus aureus infection was used to determine the relative risk of infection associated with silicone, polyurethane, polyvinylchloride, and Teflon catheters. Seven days after catheter implantation and inoculation with S. aureus, catheters were observed for gross purulence and quantitatively cultured. Silicone catheters were found to have a greater risk of grossly apparent infection (purulence) and a greater number of organisms removed from catheters by quantitative culture than the other three catheter materials (P < .01). The risk of infection associated with silicone catheters decreased (P < .05) if the S. aureus inoculation was delayed for 2 days or if the catheters were preincubated in the subcutaneous space prior to insertion. The histology of the inflammatory response around the four catheter materials was evaluated at either 2 or 7 days after catheter insertion with or without S. aureus inoculation. Silicone catheters had greater associated inflammation (P < .05) with or without S. aureus inoculation. These results suggest that silicone catheter materials may have unique properties that increase the risk of infection after implantation. Further studies should be done to understand the mechanism(s) of these observations.

Subcutaneous, catheter-related inflammation in a rabbit model correlates with peripheral vein phlebitis in human volunteers.

In the development of a polyurethane vascular catheter with anti-infective properties, it became desirable to develop a measure of tissue inflammation. This was investigated in a rabbit model by implanting uncoated catheters and catheters coated with heparin (HEP), chlorhexidine (CH), or CH/HEP in the subcutaneous space with or without 10(4) Staphylococcus aureus. At intervals of 2, 4, and 7 days after implantation, animals were sacrificed; tissue blocks containing catheters were removed and preserved with formaldehyde; and sections were stained with hematoxylin and eosin. Using a histologic index, 240 sections (10 for each experimental condition) were evaluated by two investigators blinded to experimental conditions. Uncoated catheters or catheters coated with CH alone had a lower histologic index (less inflammation) than catheters coated with HEP alone or CH/HEP (P < .05). When catheters were inoculated with S. aureus, those coated with CH, with or without HEP, had a lower histologic index than uncoated catheters (P < .05). Next, 30 volunteers had a control catheter inserted in a vein in one forearm and a catheter coated with either CH alone or CH/HEP in a vein in the other forearm. After 96 h of observation there was a greater risk of phlebitis associated with CH/HEP catheters than control catheters (P < .05), and no difference in the risk of phlebitis between CH catheters and control catheters (P = 0.43). Thus, the amount of inflammation around the catheter in the subcutaneous space of rabbit correlated with the risk of peripheral vein phlebitis.

Efficacy of antibiotic-coated catheters in preventing subcutaneous Staphylococcus aureus infection in rabbits.

Vascular catheters coated with antiinfective compounds were evaluated as to their ability to prevent Staphylococcus aureus catheter infection in a rabbit model. Zones of inhibition of agar surface-plated S. aureus demonstrated the following hierarchy: dicloxacillin and clindamycin were each better than fusidic acid or chlorhexidine, which were better than ciprofloxacin, cefotaxime, or cefuroxime. In vivo half-lives of inhibitory activity for clindamycin and dicloxacillin were 5.6 and 17.7 h, respectively, with apparent first-order kinetics. Chlorhexidine disappeared in vivo with apparent two-compartment kinetics: first-compartment t1/2, 16.8 h; second-compartment t1/2, 115.6 h. In a rabbit model, dicloxacillin, clindamycin, fusidic acid, and chlorhexidine decreased the risk of infection compared with uncoated control catheters (P < .05). For dicloxacillin, clindamycin, and chlorhexidine, this was true even if the S. aureus inoculation was delayed 48 or 96 h after catheter implantation. These data suggest that vascular catheters with antiinfective coatings should be investigated further in hospitalized patients.

Efficacy of dicloxacillin-coated polyurethane catheters in preventing subcutaneous Staphylococcus aureus infection in mice.

In a mouse model, dicloxacillin-coated polyurethane catheters or control (uncoated) catheters were placed subcutaneously and then Staphylococcus aureus was inoculated at the time of insertion, 24 or 48 h later. The in vivo half-life of the antibiotic was 11 to 16 h. When 10(5) CFU of S. aureus were inoculated at the time of catheter insertion, dicloxacillin-coated catheters kept the number of S. aureus removed from catheters by sonication below 10(2) CFU at 12, 24, 48, and 96 h after inoculation compared with titers greater than 10(3.5) CFU for control catheters (P less than 0.05). When S. aureus was inoculated 24 h after catheter insertion, control catheters averaged greater than 10(2) CFU of S. aureus removed compared with less than 10(1.5) CFU for the dicloxacillin-coated catheters (P less than 0.05). No difference was found between coated and control catheters when S. aureus was inoculated 48 h after catheter insertion, but S. aureus titers averaged less than 10(2) CFU for all experimental groups. Our data suggest that in mice, regional prophylaxis of S. aureus subcutaneous space infection is feasible with catheters coated with dicloxacillin and that the presence of antibiotic is only necessary for the first 24 to 48 h.

Bulk, surface, and blood-contacting properties of polyetherurethanes modified with polyethylene oxide.

The bulk, surface, and blood-contacting properties of a series of polyether polyurethanes based on polyethylene oxide (PEO) (MW = 1450), polytetramethylene oxide (PTMO) (MW = 1000), and mixed PEO/PTMO soft segments were evaluated. The effect of varying the weight percentage of PEO, and thus the overall polarity of the mixed soft segment phase, was investigated. Two polymer blends prepared from a PTMO-based and a PEO-based polyurethane were also studied. Differential scanning calorimetry (DSC) and dynamic mechanical analysis indicated that the polyurethanes based on either the PEO or the PTMO soft segments are relatively phase mixed. The degree of phase mixing in the polymers increased with increasing weight fraction of PEO. As expected, water absorption and the hydrophilicity of the polymer increased with increasing PEO soft segment content. In vacuum, the PEO-rich polymers have a lower concentration of soft segment at the surface, possibly due to the migration of the polar PEO segments away from the polymer/vacuum interface. The blood-contacting results indicated that the higher PEO-containing polymers were more thrombogenic than the pure PTMO-based polyurethane. A threshold concentration of PEO in the polyurethane appeared to be required before the blood-contacting properties were significantly affected.

Estimation of surface-bound heparin activity: a comparison of methods.

We compared two assays for estimating the amount of active heparin bound to a catheter surface: 1) a kinetic assay based on the inactivation of thrombin by antithrombin III, and 2) thrombin uptake. Both assays were used to estimate the amount of heparin activity on a series of catheters coated with no heparin, covalently bound heparin, and ionically bound heparin. The kinetic assay produced estimates of surface-bound heparin activity and showed that some binding methods resulted in destruction of most of the heparin's biologic activity. In contrast, the thrombin uptake assay did not correlate with the amount of heparin activity on the catheter surface. Substantial thrombin uptake was found on surfaces coated with no heparin or inactive heparin, while low thrombin uptake was found on surfaces with high levels of heparin activity in the kinetic assay. We conclude that: 1) a kinetic assay based on the heparin accelerated inactivation of thrombin by antithrombin III can be used to estimate the amount of active heparin bound to a catheter surface, and 2) thrombin uptake studies do not correlate with heparin activity and do not predict which heparin binding method will result in the highest concentration of active heparin on the catheter surface.

In vivo biocompatibility of catheter materials.

The inflammatory response to four different catheter materials was quantitatively characterized using an in vivo cage implant system over a 21 d implantation period. The greatest differences between materials were observed at day 4, where the total leucocyte concentration in the exudate decreased in the following order: AE-PVC greater than A-PU greater than D-PU1 greater than D-PU2. Similar trends were observed for the polymorphonuclear leucocyte (PMN) and macrophage concentrations at day 4. At day 7, this trend continued, but by day 21 the total leucocyte concentration, PMN concentration and macrophage concentration had decreased to comparable values for all materials. The extracellular alkaline phosphatase activity at day 4 was lowest for the AE-PVC exudate samples. Similar results were observed for the extracellular acid phosphatase activity but after that time point no significant differences were observed. From these results, it appears that AE-PVC is least biocompatible compared with the other three catheter materials, which were polyurethanes.

An in vivo method for the evaluation of catheter thrombogenicity.

A new method has been developed to evaluate the relative thrombogenicity of vascular catheters. The technique provides a means to quantitatively differentiate between catheters made from different polymeric materials. Autologous In-111 labeled platelets were infused into a dog model and catheters were then inserted into the external jugular vein of the dog. The neck region was scanned using gamma camera imaging. Comparisons between catheter materials were made using computer generated uptake slopes during the first 40 min of the scan. In addition to scintigraphy, visual assessment of thrombus deposition, thrombus weight, platelet deposition, and scanning electron microscopy were used to validate the technique. Poly(vinyl chloride), polyurethane, heparinized polyurethane, and silicone catheter materials were tested. It was found that heparinized polyurethane was the least thrombogenic of all materials evaluated.

Platelet interaction with synthetic copolypeptide films.

Kinetic and equilibrium studies of blood platelet binding to copolypeptide films show that attachment and serotonin release are not dependent upon the composition of the copolypeptide. Data may be explained by postulating that platelets frequently collide elastically with the surface but leave behind material that modifies subsequent behavior. Similarly, material released from platelets adsorbs at the interface and the extent of attachment and serotonin release are modified and controlled by these adsorbed species. Basically, if the platelet is exposed to a clean surface, its collision with the surface leads to activation and release. In the presence of inert protein, the collision is cushioned by the protein and platelets do not attach or release to any extent. Finally, if protein (or other entities) released from the platelet provide attachment sites, then attachment occurs without release. It is postulated that the behavior of platelets at surfaces is controlled by these interrelated processes.