Catheter-Related Infection and Ultrasound Detection of Central Venous Catheter Thrombosis

Abstract & Commentary

Synopsis: Detection of central venous catheter thrombosis by ultrasound may provide an early warning system for the presence of catheter-related infection.

Source: Lordick F, et al. Ultrasound screening for internal jugular vein thrombosis aids the detection of central venous catheter-related infections in patients with haemato-oncological diseases: A prospective observational study. Br J Haematol. 2003;120:1073-1078.

Lordick and colleagues in Munich used ultrasound screening to prospectively monitor the development of thrombosis in 43 patients with malignancies who had a vascular catheter in an internal jugular (IJ) vein for at least 5 days. The catheters had been inserted using the Seldinger technique with ultrasound guidance. Of the 43 polyurethane catheters, 3 were single lumen, 27 double lumen, and 13 triple lumen. Thirty-six of the catheters were placed in the right IJ vein. Screening for the presence of IJ catheter-associated thrombosis was performed every 4 days by real-time B-mode ultrasound with a 7.5 MHz linear array transducer. Thirty of the patients received prophylactic low-dose heparin (most by continuous IV infusion), and 31 patients were prophylactically receiving either ciprofloxacin or trimethoprim/sulfamethoxazole.

Catheters were in place for 6-54 days (median, 14 days). Fourteen patients developed catheter-related infection (1996 HICPAC definitions), 2 had catheter colonization, 8 had exit-site infection, and 4 had catheter-related bloodstream infection. Of the 42 catheter tips that were cultured, 13 yielded bacteria, 12 of which were coagulase-negative staphylococci. Local evidence of inflammation at the exit site was noted in 9 patients.

A partial thrombus of at least 0.5 cm in diameter was detected in 13 (30%) of the 43 patients, 5 of whom were asymptomatic at the time. Complete thrombosis of the IJ vein was not observed. Thrombosis was first detected at a median duration of 11 days of catheterization (range, 4-20 days). Patients who became neutropenic were more likely to develop thrombosis than those who did not.

Twelve of the 13 patients who developed IJ thrombosis also developed infection, while 2 had infection without thrombosis, and 1 had thrombosis without infection (P < .0001). In 4 of the 14 patients with a catheter-related infection, detection of thrombus preceded the occurrence by at least 1 day or, in 1 case, the catheter was removed before clinical signs of infection developed.

Comment by Stan Deresinski, MD, FACP

It is estimated that approximately a quarter million central venous catheter-associated infections occur annually in the United States, despite progressive improvement in methodologies aimed at prevention.1 The infections that do occur are associated with significant morbidity and mortality, making their timely recognition critical to effective patient management. This small observational study suggests the possibility that ultrasound monitoring for catheter-associated thrombosis may prove to be an early warning system.

An association between vascular catheter-associated thrombosis and infection has previously been identified. In contrast to the current study, however, the detection of thrombosis was accomplished either after catheter removal or in postmortem studies.

This study does not answer the "chicken and egg" question (ie, which comes first, the infection or the thrombus). It does, however, demonstrate that, at least in some cases, the clot can be detected before there is clinical evidence of infection. The insensitivity of signs of inflammation at the insertion site has previously been demonstrated.2 In the current study, both the specificity and positive predictive values of ultrasound monitoring and clinical findings were similar (see Figure). The negative predictive value of ultrasound monitoring was somewhat greater than that of clinical manifestations (93% vs 82%) and the sensitivity of the former was markedly better (86% vs 57%). This suggests that detection of IJ catheter-related thrombus may, in some cases, provide the first evidence of impending catheter-related infection. Furthermore, the negative predictive value of 93% indicates that this method may be of modest use in "ruling out" an infected IJ catheter as the cause of fever in some patients.

If thrombosis provides the milieu in which infection may occur or propagate, then prevention or even dissolution of catheter-related clots would be of value. Heparin is routinely used as a catheter flush for this reason. While most patients in this study received low-dose heparin by continuous IV infusion, it is not stated if the infusion was via the central venous catheter. Although no mention is made of a heparin flush, a metaanalysis concluded that heparin given either by flush or systemically was effective in reducing the risk of catheter-related central venous thrombosis but did not significantly reduce the incidence of catheter-related bloodstream infection.3

A prospective randomized comparison of monthly catheter flushing with heparin alone or together with urokinase failed to demonstrate benefit of the latter.4 In a randomized trial, minidose (1 mg) daily warfarin did not reduce the incidence of central venous catheter-related thrombosis.5

Another possible approach to prevention is by the identification of individuals with an increased risk of catheter-related thrombosis. In 1 study, the relative risk of thrombosis associated with tunneled catheters in allogeneic bone marrow recipients was 7.7 in individuals heterozygous for Factor V Leiden.6 In fact, 54% of the 13 patients with this mutation developed catheter-related thrombosis, leading Fijnheer and colleagues to suggest that all bone marrow recipients be tested for this mutation.

These results require confirmation in a larger study before their applicability to the clinic can be fully assessed. Furthermore, the generalizability will also need confirmation. All the patients in this study had nontunneled catheterization of their internal jugular vein, the least preferred site for nontunneled catheters, according to current guidelines because of evidence suggesting it is associated with an excess risk of infection.1 Nonetheless, the results are intriguing and potentially useful.

Dr. Derenski is Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center.

References

1. O’Grady NP, et al. Guidelines for the prevention of intravascular catheter-related infections. Infect Control Hosp Epidemiol. 2002;23:759-769.

2. Safdar N, Maki DG. Inflammation at the insertion site is not predictive of catheter-related bloodstream infection with short-term, noncuffed central venous catheters. Crit Care Med. 2002;30:2632-2635.

3. Randolph AG, et al. Benefit of heparin in central venous and pulmonary artery catheters: A meta-analysis of randomized controlled trials. Chest. 1998; 113:165-171.

4. Aquino VM, et al. A prospective double-blind randomized trial of urokinase flushes to prevent bacteremia resulting from luminal colonization of subcutaneous central venous catheters. J Pediatr Hematol Oncol. 2002;24:710-713.

5. Heaton DC, et al. Minidose (1 mg) warfarin as prophylaxis for central vein catheter thrombosis. Intern Med J. 2002;32:84-88.

6. Fijnheer R, et al. Factor V Leiden in central venous catheter-associated thrombosis. Br J Haematol. 2002;118:267-270.