Goal-directed ultrasonography in the intensive care unit: No more excuses!*

I n a prospective multicentered randomized trial involving 407 hemodialysis patients Maki et al (1) have demonstrated that a novel catheter lock solution consisting of 7% sodium citrate, 0.15% methylene blue, and other components (C-MB-P) significantly decreases the risk of catheterrelated bloodstream infections (CRBSIs) when compared with heparin. In this study, which is published in this current issue of Critical Care Medicine, the novel C-MB-P lock solution also provided protection against patency failure, which was comparable to heparin. This well-designed, large multicentered trial provides further evidence that a chelator containing antimicrobial lock solution provides an alternative to heparin in preventing thrombotic conclusions of catheters with the advantage of significantly decreasing the risk of CRBSI. Recent evidence has demonstrated that heparin enhances biofilm colonization of Staphylococcus aureus and other microbial organisms causing CRBSI (2– 4). Furthermore, heparin has no antimicrobial activity and is likely to be contaminated by various organisms leading to widespread multistate outbreaks of CRBSI (5). Furthermore, heparin as a catheter lock solution has been significantly associated with increased risk of bleeding in hemodialysis patients (6, 7). In addition, heparin-induced thrombocytopenia continues to be reported in hemodialysis patients maintained on heparin as a lock solution (8, 9) and heparin antibodies that have been detected in chronic hemodialysis patients have been associated with increased cardiovascular mortality (10, 11). All of these reasons have led to the search of alternative antithrombotic lock solutions to heparin. Chelators (such as citrate or EDTA) stand out as a unique antithrombotic alternatives to heparin as a catheter lock solution (12, 13). Unlike heparin, chelating agents destabilize and prevent the formation of the biofilm matrix, which is necessary for the microbial colonization of catheters. This occurs through the chelation of metal ions such as iron, calcium, and magnesium, which are essential components of the biofilm matrix (14, 15). Furthermore, chelators such as citrate and EDTA have antimicrobial activity against bacteria and fungi and could serve as enhancers of antimicrobial agents as has been previously demonstrated in in vitro animal and clinical studies (4, 14–24). The combination of 7% sodium citrate and methylene blue (CMB-P) has been shown to have activity against S. aureus in biofilm resulting in substantial structural changes in the biofilm matrix (25). This current clinical study is the largest clinical trial that adds to a growing number of clinical studies demonstrating that lock solutions consisting of a combination of chelators and antimicrobials (such as C-MB-P or minocycline EDTA or taurolidine–citrate) are highly effective in preventing CRBSI when compared with heparin lock (19–24). Another proof of principle demonstrated through this large multicentered trial is that novel technologies such as antimicrobial lock solutions can complement infection control best practices by significantly decreasing the rate of CRBSI to a level that approaches zero (0.24 per 1000 catheter days) in the high-risk hemodialysis patient population. The rate of CRBSI reported in patients with longterm hemodialysis catheters has ranged from 2–5 per 1000 catheter days (1). However, through the implementation of rigorous infection control best practices, the rate of CRBSI in the control heparin arm of this study was surprisingly low at a rate of 0.82 per 1000 catheter days, yet through the introduction of this novel antimicrobial lock solution in the test arm in combination with rigorous infection control practices, Maki et al were able to achieve a 71% further reduction in CRBSI, hence significantly reducing the risk of such infections to a very low level of 0.24 per 1000 catheter days. This finding was well described by the authors in the discussion section of the article through these terms: “despite a surprisingly low rate CRBSI in the control group, a tribute to the quality of infection control practice in the study centers, patients in the C-MD-P group had a 71% reduction of CRBSI with protection against all major groups of bacterial pathogens” (1). Hence, effective novel technologies such as antimicrobial lock solutions that include chelators compliment rather than contradict infection control practices in achieve zero tolerance. Finally, a tribute to the founder and father of the field of catheter-related infections and the first author of this study, namely Dennis Maki. For more than three decades, Dennis Maki not only defined and moved the field of catheter-related infections forward like no other clinician scientist, but he is responsible for developing and championing all the major interventions that have helped reduce the risk of CRBSI to levels that approach zero (eg, maximal barrier, chlorhexidine antisepsis of the insertion site, antimicrobial impregnation of catheters, and novel lock solutions). CRBSIs that were at one time a frequent and serious complication of central catheters have become truly preventable through the great efforts and welldesigned studies of this giant in the field. For many of us who were inspired by Dr Maki, he will remain for decades, and even centuries to come, a role model of a clinician scientist and hero who made a big difference in the field of medicine and saved countless lives. Issam Raad, MD, FACP Gerald P. Bodey, Sr, MD *See also p. 613.