2002 Mathematics Subject Classification: 62P10.This study investigates the incidence of and risk factors for Central Venous Catheter (CVC) infection in intensive care patients of Military Medical Academy in Sofia. CVCs were prospectively studied in patients who had lines inserted in general or neurosurgical intensive care and were expected to have the line in situ for at least 7 days. Catheters were cultured for CVC related infections and blood culture
done when indicated. In 29% there is a CVC related infection and in 24.26%
- a CVC related sepsis. After adjustment of duration of catheterization, independent predictors of CVC related infections were type of catheter, insertion site, sex, and Acute Physiology Chronic Health Evaluation (APACHE).
Multivariate discriminant analysis was used in order to find out significantly important factors for CVC infection an sepsis. The variables entered into the model were those found to be statistically significant (p ¡ 0.005) on multivariate analysis. The criterion for entering a variable into the model was the values of Mahalanobis statistics and the corresponding values of F-statistics [11]. The software package use for statistical analysis was STATISTIKA 5.0.Partially supported by Mathind IST-2000-26015 and by Pro-enbis GTC1-2001-43031

Atanasov, D.

Prodanova, K.

Terziiski, D.

Bulgarian Digital Mathematics Library at IMI-BAS

Pliska Stud. Math. Bulgar. 14 (2003), 15–22STUDIA MATHEMATICABULGARICARISK FACTORS OF CENTRAL VENOUS CATHETERRELATED INFECTIONS IN INTENSIVE CARE PATIENTSD. Atanasov, K. Prodanova, D. TerziiskiThis study investigates the incidence of and risk factors for Central Ve-nous Catheter (CVC) infection in intensive care patients of Military Medi-cal Academy in Sofia. CVCs were prospectively studied in patients who hadlines inserted in general or neurosurgical intensive care and were expectedto have the line in situ for at least 7 days.Catheters were cultured for CVC related infections and blood culturedone when indicated. In 29% there is a CVC related infection and in 24.26%- a CVC related sepsis. After adjustment of duration of catheterization, inde-pendent predictors of CVC related infections were type of catheter, insertionsite, sex, and Acute Physiology Chronic Health Evaluation (APACHE).Multivariate discriminant analysis was used in order to find out signif-icantly important factors for CVC infection an sepsis. The variables en-tered into the model were those found to be statistically significant (p ¡0.005) on multivariate analysis. The criterion for entering a variable intothe model was the values of Mahalanobis statistics and the correspondingvalues of F-statistics [11]. The software package use for statistical analysiswas STATISTIKA 5.0.1. IntroductionDuring the last several years, the management of acutely ill patients or patientsrequiring long-term intravenous therapy has changed because of the widespread2002 Mathematics Subject Classification: 62P10Key words: Central Venous Catheter (CVC) infection, Multivariate discriminant analysisPartially supported by Mathind IST-2000-26015 and by Pro-enbis GTC1-2001-43031.16 D. Atanasov, K. Prodanova, D. Terziiskiuse of CVCs. The major medical complication associated with the use of in-travascular devices is infection. With the possible exception of pulmonary arterycatheters, CVCs have the highest reported rates of infection of all intravascu-lar catheters [4], [8]. Data from North America indicate that CVCs used for ashort-term account for 90% of all vascular catheter related bloodstream infections[1]. A multicentre Australian study found the relative risk of CVC-sepsis was 64times higher than the observed rate of sepsis with peripheral vein catheters [4].This presents a significant problem for the care of critically ill patients who arealready highly susceptible to infection due to their underlying disease, but requireCVCs for administration of medications, fluids and blood products, as well as forhaemodynamic monitoring.A number of factors may contribute to the risk of CVC-infection. Theseinclude insertion site, duration of catheterization , type of catheter, diagnosticgroup, sex, characteristics of the patients themselves, Acute Physiology ChronicHealth Evaluation score (APACHE), etc. [4], [8], [1].We undertook a prospective study of all new CVCs inserted into patients inthe intensive care unit in order to identify risk factors for CVC - infection andsepsis.2. Patients and measurementsThe study was conducted during an one-year period in the intensive care units(12-bed) of Military Medical Academy in Sofia. Patients eligible for the studywere those who had had the central line inserted in intensive care unit and wereexpected to have the line in situ for at least 7 days. 70 CVCs inserted in 68patients ( female and male) were evaluated prospectively to determine the fre-quency and risk factors associated with catheter-related infection and sepsis. 3types of catheters are used: ”Balton”, ”Cavafix” and ”Vigon”. Data obtainedfor each catheter included the patients’ medical diagnoses and APACHE score onthe first catheter day, the use of other invasive devices, clinical and laboratorydata pertaining to infection, the anatomical location of the CVC (v. subclavia,v. jugularis and v. femoralis), the condition of insertion site, the number of daysthe catheter had been in place.3. Statistical methodsA catheter related infection was suspected in 29% of the total number of lines (70)and in 24.26% there was a CVC-sepsis. Multivariate discriminant analysis wasdeveloped to identify most relevant factors predisposing to infection and sepsis.The software package STATISTICA 5.0 was used [7]. The variables entered intoRisk Factors of Central Venous Catheter Related Infections 17the model were those found to be statistically significant (< 0.05). The forwardstepwise method was used. CVC-related infection was the dependent variable.Independent variables in our model were:• The insertion site: v. subclavia, v. jugularis and v. femoralis;• The diagnostic group;• The type of CVC: ”Balton”, ”Cavafix” and ”Vigon”;• The duration of catheterization;• Sex;• APACHE: min = 2, max = 29.At the first step we found out that the most significant factor for CVC infec-tion and sepsis is ”The type of CVC” signed as ”CATHETER” (Table 1.)Wilks’ Partial F(2,66) p-level Toler. R-Sqr.Lambda LambdaCATHETER 1.00 .85 5.81 .005 1.00 0.00Table 1The level of significance is p=0.00473. The classification of the cases is givenin Table 2.Group % Corr. n i sn 100 32 0 0i 0 20 0 0s 0 16 0 1Total 47.82 68 0 1Table 2As one may notice, 100% of the cases are distinguished on the base of thevariable CATHETER. But this delimitation is not satisfactory because the cases”Infection (i)” and ”Sepsis (s)” are attached to the class of ”No infection (n)”.Table 3 and Table 4 present correspondingly the Mahalanobis distances and levelof F-statistics.INFECTION n i sn 0.00 .34 1.02i .34 0.00 .18s 1.02 .18 0.00Table 318 D. Atanasov, K. Prodanova, D. TerziiskiINFECTION n i sn – .048 .001i .048 – .212s .001 .212 –Table 4The next variable entered into the model is ”The insertion site” signed as”VENA”. The level of significance is p=0.013. The result is: both factors”CATHETER” and ”VENA” exert essential influence on the model - correspond-ingly level of significance p=0.003 and p=0.013 (see Table 5).Wilks’ Partial F(2,66) p-level Toler. R-Sqr.Lambda LambdaCATHETER .89 .83 6.47 .002 .98 .019VENA .85 .87 4.60 .013 .98 .019Table 5So, till this moment of analysis it could be seen that in the greater part of thecases ”No infection (n)” and ”Sepsis (s)” are distinguished (about 81% and 82%correspondingly) on the base of these two factors. The cases of ”Infection (i)”are equally (10 and 10) attached to the classes ”No infection (n)” and ”Sepsis(s)” (see Table 6).Group % Corr. n i sn 81.2 26 0 6i 0 10 0 10s 82.3 3 0 14Total 47.82 68 0 1Table 6These results could be interpreted as follows: the factor ”The insertion site”determines whether the infection will grow to sepsis. The Mahalanobis distancesand the level of significance of F-statistics for this model are shown on Table 7and Table 8.INFECTION n i sn 0.00 .48 2.05i .48 0.00 .60s 2.05 .60 0.00Table 7Risk Factors of Central Venous Catheter Related Infections 19INFECTION n i sn – .070 .000i .070 – .085s .000 .085 –Table 8At the next step the independent variable APACHE was entered into themodel (p=0.008). Adding this variable makes possible the categorization of thecases of ”Infection (i)” from the cases of ”Sepsis (s)” (10 to (n), 6 to (i) and 4 to(s)) (see Table 9.).Wilks’ Partial F(2,66) p-level Toler. R-Sqr.Lambda LambdaCATHETER .74 .87 4.84 .011 .95 .046VENA .77 .83 6.40 .003 .90 .099APACHE .74 .86 5.20 .008 .88 .117Table 9Group % Corr. n i sn 78.1 25 4 3i 30.0 10 6 4s 70.6 2 3 12Total 62.3 37 13 19Table 10The Mahalanobis distances and the level of significance of F-statistics for thismodel are shown on Table 11 and Table 12.INFECTION n i sn 0.00 .55 2.79i .55 0.00 1.88s 2.78 1.88 0.00Table 11INFECTION n i sn – .107 .000i .107 – .002s .000 .002 –Table 1220 D. Atanasov, K. Prodanova, D. TerziiskiAt the last step the variable ”SEX” was entered (p=0.07). This model isshown on Table 13.Wilks’ Partial F(2,66) p-level Toler. R-Sqr.Lambda LambdaCATHETER .68 .86 5.10 .008 .94 .055VENA .74 .79 7.95 .001 .85 .153APACHE .69 .84 5.84 .005 .86 .137SEX .64 .92 2.73 .072 .92 .074Table 13Using the values of the Wilks’ Lambda we can consider the contribution ofeach of the parameters in the model. The most considerable parameter is SEXwith Wilks’ Lambda equal to 0.64. The next two parameters are CATHETERand APACHE. The most nonsignificant parameter is VENA.The classification of the cases now is 10 to (n), 6 to (i) and 3 to (s).Group % Corr. n i sn 78.1 25 4 3i 30.0 10 6 4s 70.6 2 3 12Total 62.3 37 13 19Table 14So, this variable does not give better classifications of the cases. The Obtainedresults for Mahalanobis distances and level of significance of F-statistics for thismodel are similar to these shown in Table 11 and Table 12.4. DiscussionCatheters were cultured for CVC related infections and blood culture done whenindicated. In 29% there is a CVC related infection and in 24.26% - a CVCrelated sepsis. Up to 20 different risk factors for catheter related infections inintensive care patients have been reported. These relate to catheter selection andcomposition, choice of insertion site, care of insertion site, infusate and apparatus,patient characteristics and duration of catheterization. The relative importanceof one risk factor over another is difficult to assess given that in most studies onlyunivariate analysis has been performed and estimating the risk of each factor whilecontrolling the others has not been attempted.In our investigation 6 risk factors were included: type of catheter, inser-tion site, duration of catheterization, diagnostic group, sex and APACHE. WeRisk Factors of Central Venous Catheter Related Infections 21performed a multivariate analysis to assess the major determinants of catheterrelated infections in our patients and found that after controlling the durationof catheterization, the independent predictors for catheter related infection andsepsis were type of catheter (p < 0.005), insertion site (p < 0.015), APACHE(p < 0.008) and sex (p < 0.072).The fact that insertion site is more likely to influence infection has beenreported elsewhere [6], [3], [9]. The relationship CVC infection – APACHE scoresis reported in [10], [5], but in our study the level of significance is lower.Duration of catheterization and diagnostic group was not found in multivari-ate analysis to add to the risk of infection. Resent Australian and USA studiessuggested that there may be a marked increase in the risk of CVC related infec-tions in some patients with dwell times longer than 5 days. This studies testedonly for the effect of catheter type for insertion and did nor control statisticallyother risk factors. However, there is some evidence to suggest that the routinereplacement of CVCs does not necessary reduce the risk of infection [4].The variable ”type of catheter” in medical sense corresponds to differenttechniques of CVC insertion. The result that this is the most significant factorfor CVC infection and sepsis is unexpected for our medical doctors. There are asmall number of studies which include this risk factor.In our future work we plan to include about 60 new patients and add newrisk factors as microbiological parameters, number of lumens of CVC, etc. Weplan to correct our results using theory of Mixture of Continuous and CategoricalVariables in Discriminat Analysis presented by Krzanowski [2].REFERE NCES[1] P. J. Collignon. Intravascular catheter-associated sepsis: a commonproblem. Medical J. of Australia 161 (1994), 374–378.[2] W. J. Krzanowski. Mixtures of Continuous and Categorical Variablesin Discriminant Analysis. Biometrics 36 (1980), 493–499.[3] S. W. McDonald, A. J. B. McNally et al. Comparison of technicalSuccess and Outcome of Tunneled Catheters inserted via Jugular andSubclavian Approaches. J.V.I.R 11 (2000), 225–231.[4] McKinly, A., Finfer S., Ward R., Penfold J. Incidence and predic-tors of central venous catheter related infection in intensive care patients.Anesth. Intensive Care 27 (1999), 164–169.22 D. Atanasov, K. Prodanova, D. Terziiski[5] L. A. Mermel. Prevention of Intravascular Catheter Related Infections.ANN. Inter. Med. 132, 5 (2000), 391–402.[6] L. A. Mermel, Farr, B. M., Sheretz, R. J. et al. Guidelines forthe Management of Intravascular Catheter – Related Infections. Infect.Control. Hosp. Epidemiol. 22 (2001), 222–242.[7] StatSoft, Inc. (1995). STATISTICA for Windows [Computer programmanual]. Tulsa, OK: StatSoft, Inc., 2325 East 13th Street, Tulsa, OK74104, (918) 583-4149, fax: (918) 583-4376.[8] E. Tacconelli, Tumbarello M., Pittiruti F., Leone F., LuciaM.B., Caudia R., Ortona L., Eur. J. Clin. Microbiol. Infect. Dis. 16(1997), 203–209.[9] J. F. Timsit, Brunell, F., Cheval, C. et al. Use of TunneledFemoral Catheters of Prevent Catheter - Related Infection. A random-ized Controled Trial. Ann. Intern. Med. 130 (1999), 729–735.[10] J. F. Timsit, J.C. Boyer, J. M. et al.Center Vein Catheter – Re-lated Trombosis in Intensive Care Patients. Incidence Risk Factors, andRelationship with Catheter Related Sepsis. Chest 144 (1998), 207–213.[11] D. L. Vandev, P. Mateev. Statistics with PRAVETZ 82. Nauka iIzkustvo, Sofia, 1998.Dimitar AtanasovFaculty of Mathematics and InformaticsSofia University, 5 J. Boucher Str., 1407 Sofia, Bulgariae-mail: datanasov@fmi.uni-sofia.bgKrassimira ProdanovaTechnical University - SofiaFaculty of Applied Mathematics and Informaticse-mail: kprod@vmei.acad.bgD. TerziiskiMilitary Medical Academy, SofiaDepartment of Anaesthesiology and Intensive Care Medicinee-mail: dterziiski@yahoo.com

Risk Factors of Central Venous Catheter Related Infections in Intensive Care Patients

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Risk Factors of Central Venous Catheter Related Infections in Intensive Care Patients

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