Infectious Complications of Radiologically Inserted Hickman Catheters in Patients with Hematologic Disorders

4k18 0014 Mp 116 Tuesday Feb 03 02:09 PM SV-CVIR (v. 21, #2) 0014 (1357)

Cardiovasc Intervent Radiol (1998) 21:116–121

CardioVascularand InterventionalRadiologyq Springer-Verlag New York Inc. 1998

Infectious Complications of Radiologically Inserted HickmanCatheters in Patients with Hematologic Disorders

Jeannette Bakker,1 Hans van Overhagen,1 Jenne Wielenga,2 Siem de Marie,3 Jan Nouwen,3

Marie A.J. de Ridder,4 Johan S. Lameris1

1 Department of Radiology, University Hospital Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam, The Netherlands2 Department of Hematology, University Hospital Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam, The Netherlands3 Department of Bacteriology, University Hospital Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam, The Netherlands4 Department of Epidemiology and Biostatistics, Erasmus University, PO Box 1738, NL-3000 DR Rotterdam, The Netherlands

AbstractPurpose: To assess the incidence of infections and itsinfluence on the survival of radiologically insertedHickman catheters (HCs) in patients with hematologicdisorders and to determine factors associated with pre-mature HC removal.Methods: Survival and complications of 175 HCs in115 patients were studied retrospectively. To describethe data the Kaplan-Meier method and the log-rank testwere used, using the date of HC removal due to HC-related infection as endpoint. A stratified Cox regres-sion model was used to determine explanatory factors.Results: Seventy (40%) HCs were removed prema-turely because of proven or probable HC-related infec-tions. The incidence of infection leading to HC removalwas 4.78 per 1000 catheter-days for proven HC infec-tions. Univariate analysis revealed that acute myeloidleukemia, acute lymphocytic leukemia, or treatment forthese diseases, gender, each subsequent catheter in thesame patient and insertion site increased the risk of pre-mature removal of the catheter due to infection.Conclusion: Infection is a major problem in patientswith HCs. Unfortunately, the factors associated withincreased infection rates that were found in this studycannot be influenced. Further studies are necessary todetermine the role of environmental conditions in a ra-diology suite in relation to the risk of developing acatheter-related infection.

Key words: Catheters and catheterization—Central ve-nous access, complications—Ultrasound guidance—Veins, subclavian

Correspondence to: H. van Overhagen, M.D.

Large-bore central venous catheters are used forparenteral nutrition, chemotherapy, hemodialysis, andblood sampling. Traditionally these catheters areplaced by surgeons in the operating room using eitherthe cutdown method or the percutaneous approach.During the last decade these catheters have increasinglybeen inserted by radiologists in radiology suites usingsonographic, fluoroscopic, and angiographic tech-niques. Using these techniques increases the successrate and decreases complications such as pneumotho-rax, hematothorax, perforation of the blood vessel, andcatheter malposition [1–4]. Moreover, placement in aradiology suite is reported to be easier to schedule, re-duces the time required, and is cheaper [5, 6].

At our institute, Hickman catheters (HCs) havebeen placed by radiologists in a radiology suite de-signed for invasive procedures since 1991. Despite anobserved higher technical success rate and lower me-chanical complication rate in HC placement, infectionswere felt to be our most common complication. Thisstudy was performed to determine the impact of HC-related infections in those patients who are very sus-ceptible to infectious complications, such as those withhemato(onco)logic disorders. Furthermore, we at-tempted to determine factors associated with HC-re-lated infection in an effort to develop strategies thatmay help to reduce the incidence of infections in thefuture.

Materials and Methods

Catheter survival and complications of 175 radiologically insertedHCs in 115 consecutive patients were studied retrospectively. These


J. Bakker et al.: Infections in Hickman Catheters 117

Table 1. Hematologic disorders

Diagnosis No. of patients

Acute lymphocytic leukemia (ALL) 22Acute myeloid leukemia (AML) 43Chronic myeloid leukemia with a blast crisis 3Hodgkin’s disease 2Non-Hodgkin’s lymphoma (NHL) 22Multiple myeloma 7Thrombotic thrombocytopenic purpura (TTP) 6Aplastic anemia 5Myelodysplastic syndrome 5Total no. of patients 115

Table 2. Proven and probable HC-related infections leading to HCremoval

Type of infection No. of HCs

Proven HC infection 46 (26%)Exit site infection 2Tunnel infection 6Thrombosis in association with bacteremia 9Fever associated with bacteremia, positivetip culture

29

Probable HC infection 24 (14%)Fever associated with bacteremia, sterileor absent tip culture

24

HCs represent all HCs placed in hematologic patients in the periodJanuary 1991 to December 1993. There were 68 men and 47 women,aged 16–78 years (mean 47 years), suffering from the hematologicdisorders summarized in Table 1. Patients who received a HC forother reasons, such as hemodialysis or parenteral nutrition, were notincluded in this study. Eighty patients were treated with intensivechemotherapy, 24 patients were autologous bone marrow transplantrecipients, and five patients were treated with anti-thymocyte glob-ulin (ATG). All these patients had severe neutropenia (neutrophilcounts below 0.11 109/L) for at least 2 weeks. Nonchemotherapeutictreatment such as plasmapheresis was initiated in six patients. Eightpatients eventually did not receive any treatment because they diedbefore therapy was initiated (n Å 1), their general condition wasconsidered too poor to undergo chemotherapy (n Å 3), they devel-oped pneumothorax (n Å 1) or infection (n Å 1) that necessitatedcatheter removal, or accidental removal of the catheter occurred be-fore therapy was started (n Å 2).

Hickman catheters (Gish Biomedical, Santa Ana, CA, USA andC.R. Bard, Salt Lake City, UT, USA) were placed as described pre-viously [4] in an interventional radiology suite designed for invasiveprocedures. The ventilation frequency in this suite was 12–15 timesper hour. The room was not equipped with either a high-efficiencyparticulate air filter or down-flow systems. Briefly, the procedure wasas follows. The target vein was punctured with an 18-gauge needleunder sonographic guidance using a 5.0-MHz or a 7.5-MHz trans-ducer. A flexible J-wire was introduced through the needle into thevein. A subcutaneous tunnel of approximately 10 cm was made, withthe exit pointing medially towards the sternum. The catheter waspassed through the tunnel and shortened to its appropriate length,with the tip of the catheter positioned at the junction of the superiorcaval vein and the right atrium. Introduction of the dilator and sheathand placement of the catheter were controlled by fluoroscopy. Themajority of HCs were placed by two consultant radiologists; five wereinserted by residents under supervision of the two abovementionedconsultants. We aimed to obtain aseptic conditions with the followingmeasures: hand scrub with povidone-iodine for 5 min, disinfectionof the patient’s skin with chlorhexidine 0.5%/ethanol 70%, the useof long-sleeved surgical gowns and large sterile sheets, and masksand caps for both radiologist and patient. Premedication and prophy-lactic antibiotics were not used. However, patients with leukemia andall patients with bone marrow transplantation received selective de-contamination of the gastrointestinal tract with ciprofloxacin and itra-conazole prior to and during chemotherapeutic therapy.

The left subclavian vein was preferentially used for venous accessbecause catheter insertion on this side is facilitated by the more ob-tuse angle with the brachiocephalic vein in comparison with the rightside. One hundred and two HCs were inserted using the left subcla-vian vein and 65 using the right subclavian vein. The femoral veinwas used for catheter placement in only five cases. In three cases thesite of HC insertion could not be assessed retrospectively. Includingthe period prior to the study, 110 of the 175 HCs were the patient’sfirst HC, 42 were the second, 16 were the third, six were the fourth,and one was the fifth catheter. During the study period 75 patients

underwent placement of one HC, 26 of two HCs, nine of three HCs,four of four HCs and one of five HCs. Maintenance of HCs was doneby a team of trained nurses who disinfected the exit site with chlor-hexidine and changed sterile dressings daily. Handling of HCs waslimited to once daily and was done under strict aseptic conditions. Inthose cases when a HC was removed because of catheter-related in-fection and replaced by a new one, a period of 24 hr with sterileblood cultures and no signs or symptoms of infections, was alwaysobserved.

Hospital charts, radiological and bacteriological reports werestudied retrospectively to assess the duration of continuous catheter-ization, reasons for catheter removal and complications during andfollowing HC insertion. Special attention was given to HC-relatedinfections. HC infection was considered proven in cases of an exitsite infection, a tunnel infection, thrombosis in association with bac-teremia, and fever associated with bacteremia when the tip of theremoved HC grew identical bacteria. HC infection was consideredprobable but not proven in cases of fever in association with bac-teremia due to typical pathogens such as Staphylococcus epidermidis,Staphylococcus aureus, or Corynebacterium spp., but sterile or ab-sent cultures of the catheter tip after removal. Fever or clinicallysuspected sepsis in association with sterile blood cultures were notconsidered a HC-related infection. When a neutropenic patient de-veloped fever the initial standard antibiotic regimen consisted of to-bramycin and amoxicillin/clavulanate (Augmentin). As soon as HCinfection was suspected the antibiotic regimen included vancomycin.

Because the different catheterization periods had to be taken intoaccount, the risk of premature HC removal due to infection was stud-ied using survival analysis. The Kaplan-Meier method was used todescribe the data, using the date of HC removal due to catheter-related infection as endpoint. Differences in survival were tested us-ing the log-rank test. Because of the significant difference in survivalbetween the first, second, and third or subsequent HCs, a stratifiedCox regression model with those three strata was used to determineexplanatory factors. The potential covariables used were: age, gender,period of the year when the catheter was inserted, site of catheterinsertion, disease, and treatment. The multivariate model was builtusing stepwise forward selection.

Results

Complications related to HC insertion were encoun-tered in four (2.3%) patients. Pericatheter bleedingwhich could be managed conservatively was seen inthree patients. One patient developed a pneumothoraxthat required chest tube drainage.

Seventy (40%) HCs were removed prematurely be-cause of either proven or probable catheter-related in-


J. Bakker et al.: Infections in Hickman Catheters118

Fig. 1. Survival of the patient’s first, second,and third or subsequent Hickman Catheter(HC).

fections; duration of catheterization in this groupranged from 4 to 427 (median 28) days. Infection wasproven in 46 (26%) and probable in 24 (14%) catheters(Table 2). Twenty-seven (15%) HCs were removedprematurely because of noninfectious complications(dislodgement n Å 11, fever of unknown origin n Å 9,venous thrombosis n Å 4, catheter blockage n Å 2,hypersensitivity n Å 1). These catheters were in situfor between 1 and 150 (median 15) days. The remain-ing 78 (45%) HCs were in situ with no infections for3–321 (median 48) days; 25 patients died with thecatheter in place, 52 HCs were removed electively andone patient was referred to another hospital with thecatheter in place.

The incidence of infection leading to catheter re-moval was 4.78 per 1000 catheter-days for proven HCinfection and 7.28 when probable HC infections wereincluded. The median catheter survival until HC re-moval due to HC-related infection (proven and proba-ble) was 139 days for patients’ first HCs, 69 days forsecond HCs, 22 days for third HCs, and 45 days forfourth HCs. The single patient’s fifth HC was in situfor 3 days when the patient died; death was not asso-ciated with HC-related infection. Comparing patients’first, second, and third or subsequent HCs with the log-rank test showed a significant difference in catheter sur-vival (p Å 0.03) (Fig. 1). Thus, for the univariate andmultivariate analyses we corrected for the number ofprior HC insertions by stratification.

Univariate analysis of catheter survival until HCremoval due to HC-related infection (proven and prob-

able) did not show significant effects for age (pÅ 0.61),sex (p Å 0.23) or period during which the HC wasinserted (pÅ 0.58). HCs inserted through the right sub-clavian vein had a significantly higher chance of pre-mature removal due to infections compared with thoseinserted through the left subclavian vein (p Å 0.04).The hematologic diagnosis was a significant risk factorfor premature HC removal due to infection (pÅ 0.003).Patients with acute myeloid leukemia (AML) and acutelymphocytic leukemia (ALL) had a higher risk of pre-mature catheter removal due to infection. There was nostatistically significant difference between those withAML and ALL (p Å 0.25). Figure 2 shows the survivalcurves of patients’ HCs for the various groups of he-matologic diagnoses. Treatment was used as a time-dependent factor; there was a significant effect on therate of HC-related infections (p Å 0.003) (Table 3).Treatment for AML and the first course of chemother-apy for ALL were associated with a significantlygreater chance of developing catheter-related infectionleading to removal compared with therapies for otherdiseases.

Multivariate analysis resulted in a model withonly gender and hematologic diagnosis as significantrisk factors (Table 4). That patient’s gender is a sig-nificant risk factor according to the multivariate anal-ysis but not in the univariate analysis can beexplained by the fact that more women had a hema-tologic diagnosis associated with poor catheter sur-vival. Due to this, the female gender being a riskfactor is obscured by the hematologic diagnosis in



Fig. 2. Survival of HCs for various hemato-logic disorders.

Table 3. Type of treatment and the relative infection rate (univariateanalysis)

Treatment Relative infectionrate (95% CI)

Chemotherapy for AML 1First course of chemotherapy for ALL 1.7 (0.9–3.2)Second and subsequent courses ofchemotherapy for ALL

0.6 (0.3–1.4)

Bone marrow transplantation 0.5 (0.2–1.2)Others 0.3 (0.1–0.8)

CI Å confidence interval

Table 4. Gender and diagnosis and their relative infection rate (mul-tivariate analysis)

Factor Relative infectionrate (95% CI)

GenderMale 1Female 1.9 (1.1–3.2)

DiagnosisAML 1ALL 1.8 (1.0–3.1)NHL, Hodgkin 0.3 (0.1–0.9)TTPa —Others 0.4 (0.1–1.2)

CI Å confidence intervala No infections for this diagnosis

the univariate analysis but not in the multivariateanalysis.

Ninety-two tips of HCs were cultured after re-moval. Staphylococcus epidermidis was cultured in 40(43%) and other microorganisms (S. aureus, Entero-coccus spp., yeast) in six (7%) cases. Forty-six (50%)catheter tips remained sterile. One HC was not removedand catheter tip cultures were not obtained in the re-maining 82 HCs.

Discussion

There is growing evidence that radiologically guidedplacement of central venous catheters is superior toblind insertion with regard to the technical success rateand the number of short-term complications [1–4].This is confirmed by the present study, in which a se-

rious complication due to catheter insertion, a pneu-mothorax, was observed in only one (õ1%) of 175inserted HCs.

In this study the incidence of proven catheter in-fections leading to removal of the catheter was 4.78per 1000 catheter-days. Direct comparison of our re-sults with those of others is difficult because of manyfactors. The various definitions used in the literaturefor HC infections can influence the calculated infec-tion rates. Differences in patient populations betweenseveral studies may also influence the reported in-fection rates. Our population mainly consistedof patients with leukemia or other hematologic ma-lignancies with second- or third-line chemotherapy.


J. Bakker et al.: Infections in Hickman Catheters120

Several other studies reported on a mixed populationwith various malignant and nonmalignant disorders[8–10]. Infection rates found nowadays may behigher than those published earlier, due to the moreaggressive chemotherapeutic regimens used, leadingto prolonged severe neutropenia and the existence ofmultiple resistant strains of microorganisms. In ad-dition, the introduction of ciprofloxacin in selectivedecontamination of the gastrointestinal tract has ledto an increase of infections with Staphylococcus ep-idermidis and other gram-positive bacteria. Anotherreason for caution in comparing results between stud-ies is the fact that some studies evaluated not onlytunnelled central venous catheters but included cath-eters with a subcutaneous reservoir; the latter areknown to have a lower risk of infection [11]. Finally,the difference in infection rate could be explained bythe different environment during insertion, i.e. radi-ology suite or operating room. Although several au-thors have suggested there is no increase of infectiondue to insertion in radiology suites [4, 9, 12–15], aprospective randomized study has not been carriedout.

In this study several factors were associated witha higher risk of developing a catheter-related infec-tion. Unfortunately, none of these factors can be in-fluenced in order to reduce infection rates. It is clearthat patient’s gender and underlying disease cannotbe changed. Other risk factors, such as specific che-motherapeutic regimens for AML and ALL, are dif-ficult to alter. These therapies have become moreaggressive during recent years and lead to severe pro-longed neutropenia, but are the only hope of obtain-ing better cure rates. Contrary to the results reportedby Press et al. [7] we found that each subsequentcatheter in the same patient had a higher risk of be-coming infected. This may be explained by the factthat once there is an infectious focus in a patient (sub-clinically), subsequent periods of bacteremia willcolonize the catheter. This problem may be reducedby allowing a period of more than 24 hr before a newHC is placed, but it is doubtful whether this is pos-sible in patients with hematologic disorders, in whomintensive (chemo)therapy and monitoring require thepresence of a central venous catheter. The higher riskof premature HC removal due to infection for HCsinserted through the right subclavian vein comparedwith those inserted through the left subclavian veinmay be explained by the fact that in the present studyHCs were preferentially inserted in the left side. Theright side was generally used in those patients re-quiring a new HC after the first HC had been removeddue to various reasons including infection. There-fore, the insertion site is again a risk factor that can-not be influenced.

Due to the retrospective nature of this study wewere not able to study all factors possibly associatedwith HC infections. As HCs are increasingly insertedin radiology departments, a factor that certainly hasto be studied is the condition of the air in the radi-ology suite where HCs are inserted. Earlier studieshave shown that air condition can influence infectionrates after orthopedic procedures in which prostheticmaterials were implanted [17, 18]. This has led toguidelines for air conditions in operating rooms fordifferent surgical procedures. However, the signifi-cance of these guidelines for HC insertion remainsto be determined.

In conclusion, infection is a major problem in he-matologic patients with a HC. Factors associated withincreased risk of HC infection in our study were gen-der, hematologic disease, treatment for specific dis-eases, and repeated catheter insertion. Unfortunatelynone of these factors can be influenced. Further studyis required to determine other risk factors possibly as-sociated with HC infections.

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Infectious Complications of Radiologically Inserted Hickman Catheters in Patients with Hematologic Disorders