10

Vol. 3. No. 1 January–March 2012

Research Report

CATHETER DURATION AND THE RISK OF SEPSIS IN PREMATURE

BABIES WITH UMBILICAL VEIN CATHETERS

Hartojo1, Martono Tri Utomo2

1
Division of Neonatology, Department of Child Health,
Husada Utama Hospital
2
Department of Child Health, Dr. Soetomo General Hospital

ABSTRACT
Umbilical catheters are frequently required in the management of severely ill premature babies. The risk of complications may
increase with duration of UVC use. Objective: To determine whether the risk of central line-associated bloodstream infections (CLA-
BSIs) and sepsis remained constant over the duration of umbilical vein catheters (UVCs) in high-risk premature neonates. Methods:
retrospective analysis. The data were collected from the medical record of high risk premature neonates who had a UVC placed in
neonatal care unit of Husada Utama Hospital between April 1st 2008 to April 30th 2011 with purposive sampling. Catheter duration
was observed before and after 14 days on placement. Blood and UVC culture was performed to establish the risk of CLA-BSIs and
sepsis. Chi-square and logistic regression analysis were performed in the laboratorium data. Result: A total 44 high risk premature
babies with UVCs were enrolled (sepsis group: n = 23 and non sepsis group: n = 21). Baseline demographics were similar between
the groups. 15 babies in sepsis group have UVCs duration > 14 days, and 8 babies have UVCs < 14 days (p = 0.533). Days of UVC
< 14 days show UVCs culture performance in 11 babies with positive evidence, blood culture performance shows negative in 21 babies
(p = 0.516). Days of UVC >14 days show blood culture performance in 11 babies with positive evidence, UVCs culture performance
is negative in 18 babies (p = 0.456). Burkholderia cepacia and Klebsiella pneumonia mostly appeared in blood culture performance.
25% of UVC culture performance shows Pseudomonas aeroginosa. Conclusions: The catheter duration have no significant difference
in risk of sepsis in premature babies with Umbilical Vein Catheters.

Key words: Premature babies - Sepsis – days of UVC – CLA-BSIs

INTRODUCTION 19% of patients with a UVC, infectious adverse events in

5 to 26% and thrombosis in 2 to 26%.4.5
Umbilical catheters are frequently required in the The incidence of neonatal sepsis is approximately
management of severely ill neonates. 1.2 Umbilical- 1 to 10 cases per 1000 live births and 1 per 250 live
vein catheters (UVCs) can be used for intravenous premature births. The incidence rates of neonatal infection
administration of parenteral nutrition, hypertonic solutions, in several referral hospitals in Indonesia is approximately
blood products, and medication. Umbilical-artery catheters 8.76%–30.29% with the mortality rate is 11.56%–49.9%.
(UACs) can be used for blood sampling and continuous The incidence rates of neonatal sepsis in several referrals
monitoring of blood pressure. However, the advantages hospital in Indonesia is 1.5%–3.72% with the mortality
of umbilical catheters must be carefully balanced against rate is 37.09%–80%.6
the potential risks. Several life threatening complications Because the risk of complications may increase with
have been associated with the use of umbilical catheters duration of use, UVCs are often removed after relatively
including catheter-related infections, intestinal necrosis, short periods and replaced with percutaneous central
thrombosis, cardiac arrhythmias, myocardial perforation, venous catheters (PCVCs) for maintenance of long-term
as well as pleural and pericardial effusion.1.2.3 According fluid and nutritional status.2.7 On the basis of these limited
to the literature, mechanical adverse events occur in 5 to data, the Centers for Disease Control and Prevention
Hartojo: Catheter Duration and the Risk of Sepsis in Premature Babies 11

currently recommend use of UVCs be limited to 14 days. was defined as the catheter tip being visible between the
In a retrospective review of 230 infants with birth weights 9th and 10th thoracic vertebrae on a chest X-rays. Catheters
1251 g who were admitted to our NICU and required a were sutured in place into the umbilical cord, and tape was
UVC and/or PCVC, the apparent proportion of catheters then used to secure the catheter to the infant's abdomen.
remaining infection free at 20 days (the time at which the
last UVC was removed) was 89% for UVCs and 73% for Blood and tips UVC tips Cultures
PCVCs.8 Blood culture test was performed in premature babies
UVCs comprise a large proportion of central lines with suspected sepsis based on clinical symptoms, complete
inserted in the NICU. Central line–associated bloodstream blood test and CRP using VITEX method. Whole blood
infections (CLA-BSIs) can complicate PICCs. An estimated (0.3–1.0 mL) was placed in sterile Isolator tubes and
80 000 CLA-BSIs occur in the United States every year. transported to the microbiology laboratory. Blood was
The mortality rate for these CLA-BSIs remains unclear, streaked onto blood and chocolate agar plates and then
but recent studies demonstrated a range of 4% to 20%. incubated for 5 days under aerobic conditions. UVC
CLA-BSI extends patient length of stay by an average of tips Cultures were placed in an automated reader (Bact-
7 days, and the attributable cost is $3700 to $29 000 per alert; Biomerieux). Any positive or potentially positive
infection.3.5.8 cultures were Gram-stained, streaked on to blood and/or
In this study, we prospectively examined catheter- chocolate agar plates (depending on the likely pathogen),
related bacteremia and associated sepsis complications in and incubated under aerobic conditions. Organisms were
long-term use of UVCs. isolated by either culture system identified with standard
microbiologic techniques.

Definitions
METHODS
Clinical Sepsis
Subjects The definition of infection included symptomatology
The study was retrospectively done at NICU of Husada (eg, temperature instability, increased ventilator settings,
Utama hospital, conducted for 3 years (April 1st 2008 until increased apnea, bradycardia or desaturations, feeding
April 30th 2011). The premature infants with birth weights intolerance, lethargy, or blood pressure instability) and
less than 2000 g who had a UVC placed on NICU admission either a single positive blood culture for prospectively
were eligible for the study. Infants who required a UVC defined definite pathogens or multiple positive cultures
for exchange transfusion, infants with gastrointestinal (≥ 2 within 48 hours) for other organisms from usually
abnormalities including gastroschisis and omphalocele, sterile site(s) (blood, catheter tip, urine, or cerebrospinal
or infants with congenital heart disease with intra cardiac fluid, with at least 1 positive culture from the blood).1.9.10
shunting were excluded. The parents or legal guardians of
the patients gave informed consent before enrollment. CRBSI
Bacteremia/fungemia in a patient with an intravascular
Umbilical Catheterization catheter with at least 1 positive blood culture obtained
Placement of a UVC was attempted in infants < 2000 from a peripheral vein, clinical manifestations of infections
g on admission to the NICU. Either a single or double (fever, chills, and/or hypotension), and no apparent source
lumen catheter (3.5F diameter, Polyurethane 1270 Catheter; for the BSI except the catheter. One of the following should
Vygon Healthcare, Gloucestershire, UK) was inserted be present: a positive semi quantitative (>15 CFU/catheter
under sterile conditions. A double-lumen UVC was used segment) or quantitative (>103 CFU/catheter segment
if it was technically possible to place one. Care of the catheter) culture whereby the same organism (species and
catheters was standardized. Catheters were attached to antibiogram) is isolated from the catheter segment and
transducers, was changed every 24 hours if the infused peripheral blood; simultaneous quantitative blood cultures
concentration of dextrose was >12.5 g/L and every 72 with a >5:1 ratio CVC versus peripheral; differential period
hours for concentrations of dextrose <12.5 g/L. All UVCs of CVC culture versus peripheral blood culture positivity
had continuous infusion of solutions in the main port. Both of >2 hours.8.11.12
infusion and flush solutions contained heparin (1.0 IU/mL
for infants >1000 g and 0.5 IU/mL for infants <1000 g or Statistical Analysis
on total parenteral nutrition). All catheter connections were Data are presented in distribution tabulation and data
checked hourly to guard against any disconnection. analysis was performed with a computer assisted statistical
Catheter placement was confirmed with a chest and package (SPSS ver. 12.0). Descriptive analysis of catheter
abdominal radiograph. The catheter placement was adjusted duration and risk of sepsis, UVCs and blood culture of the
to place the catheter tip at the inferior vena cava/right atrial patient were calculated. Chi-square analysis and logistic
junction. We had confirmed the depth of catheter tips using regression were performed in the laboratorium data.
antero-posterior chest X-rays. Ideal position of the UVC
12 Indonesian Journal of Tropical and Infectious Disease, Vol. 3. No. 1 January–March 2012: 10−14

RESULTS with days of UVC less than 14 days were in the risk of
sepsis. 8 babies with days of UVC more than 14 days were
Data from April 1st 2008 until April 30th 2011 revealed in the risk of sepsis.
the premature babies with UVCs were 44 samples. All of
them were eligible for analysis, 23 in sepsis group and 21
in no sepsis group. The characteristics of the sample are Table 3. Catheter Duration and The Risk of CLA-BSIs
listed in table 1.
UVC Culture Blood Culture
Days of UVC
+ – + –
Table 1. Characteristic of High Risk Premature Neonates Who < 14 days 11 (68.8) 5 (31.2) 7 (25) 21 (75)
had a UVC Placed in NICU
> 14 days 10 (35.7) 18 (64.3) 11 (68.8) 5 (31.2)
Parameters Sepsis No Sepsis P Chi Square X2 test p = 0.516; p = 0.456
n = 23 (%) n = 21 (%)
Gender .121 Table 3 shows that days of UVC have no significant
Female 7 (38.9) 11 (61.1) difference in UVC and blood culture result in premature
babies treated in NICU Husada Utama hospital. Days of
Male 16 (61.5) 10 (38.5)
UVC less than 14 days show UVC culture performance in
Birth weight (g) 1428.3 1450.0 .52
(SD 324.33) (SD 321.71)
11 babies suspected sepsis is positive, in fact blood culture
performance shows negative in 21 babies. Days of UVC
Gestational age .467 more than 14 days show blood culture performance in 11
< 30 week's 9 (50.3) 7 (43.8) babies with blood culture positive evidence, even though
UVC culture performance is negative in 18 babies.
> 30 week's 14 (50) 14 (50)
Apgar score .322
≤6 8 (61.5) 5 (38.5) Table 4. Pathogens that Caused CLA-BSI in Neonates with
UVCs in Premature Babies
>6 15(48.4) 16 (51.6)
Mechanical .068 Blood UVC
ventilator Microorganisms Culture Culture
Yes 18 (62.1) 11 (37.9) n % N %
No (n-CPAP) 5 (33.3) 10 (66.7) Acinetobacter baumanii 1 2.3 5 11.4
Burkholderia cepacia 4 9.1 4 9.1
Table 1 shows that the results have no significant Candida albicans 1 2.3 0 0
difference based on the gender, birth weight, gestational Enterobacter asburie 1 2.3 0 0
age, apgar score in premature babies with sepsis risk Klebsiella pneumoniae 4 9.1 3 6.8
treated in NICU Husada Utama hospital. However baby
Escherichia coli 0 0 4 9.1
with mechanical ventilator shows to have higher risk
Pseudomonas aeroginosa 0 0 11 25
compared with n-CPAP. In this case: 18 premature babies
Enterobacter cloacae 0 0 2 14.5
with mechanical ventilator and 5 with n-CPAP affected by
Stenotrophomonas maltophila 1 2.3 0 0
sepsis. Babies with apgar score less than 6 during the labor
have higher risk affected by sepsis, on the other hand apgar No organism growth 12 27.3 15 34.1
score more than 6 shows lower risk.
Table 4 shows the types of microorganism appeared in
blood and UVC culture in 44 premature babies treated in
Table 2. Catheter Duration and The Risk of Sepsis in Premature NICU Husada Utama hospital. Burkholderia cepacia and
Babies Klebsiella pneumonia mostly appeared in blood culture
performance. 25% of UVC culture performance shows
Sepsis Pseudomonas aeroginosa. Of 23 babies suspected sepsis
Days of UVC
Positive n(%) Negative n(%) 12 babies show no organism growth on blood culture
< 14 days 15 (53.6) 13 (46.4) performance while 15 babies show no organism growth
on UVC culture performance.
> 14 days 8 (50) 8 (50)
2
Chi Square X test p = 0.533
DISCUSSION
Table 2 shows that days of UVC have no significant
difference in the risk of sepsis in premature babies treated CLA-BSIs are a common cause of morbidity and
in NICU Husada Utama hospital. In this study 15 babies mortality among neonates.1.3.6.10 Several factors have been
Hartojo: Catheter Duration and the Risk of Sepsis in Premature Babies 13

shown to contribute to the pathogenesis of nosocomial CLA- prevalent are the Pseudomonas sp (7%) and the Escherichia
BSI. Host-related risk factors include age, immunologic coli (6%). Infection by Candida SP is responsible for the
immaturity, and severity of underlying disease.12.13 In this remaining 5% of catheter-related infections.1.2.19 Coagulase
study shows that gestational age < 30 weeks and mechanical negative staphylococcus was the dominant infection
ventilator have contributed the risk of CLA-BSI. (55.6%) within the first 2 weeks, whereas Gram negative
The risk profiles of a long term UVC to a long-term bacteria were dominant pathogens (58.3%) after the first
PCVC have seldom been compared. On the basis of 2 weeks.20.21 However, the most frequent microorganism
these limited data, the Centers for Disease Control and isolated in cultures in this study was the Pseudomonas
Prevention currently recommend use of UVCs be limited aeroginosa.
to 14 days. However, a survey of nursery directors revealed To avoid contaminating central venous catheters,
that some NICUs leave UVCs in place for a longer period several measures should be implemented in their insertion
of time.7.14.15 The limited data available after 14 days in and maintenance.10.11 Central catheter insertion, whether
this study suggest the possibility of increased infection. it is a PICC or a UVC, should be aseptic and include
Duration of catheter > 14 days show 11 babies with measures of barrier precaution such as wearing a cap, mask,
blood culture positive evidence, although not statistically sterile gown, sterile gloves and drapes. It is recommended
significant, would have potential clinical significance if it to wash hands with chlorhexidine detergent or alcohol
were to be substantiated. gel before and after contacting with the catheter during
Migration of skin organisms at the insertion site into the UVC maintenance. The dressing has to be changed every
umbilical catheter tract with colonization of the catheter tip seven days or when it is wet or for other reasons taken off,
is the most common route of infection for centrally inserted, change taps, equipment and extensions every 72 hours and
shortterm catheters.4.8.9 Contamination of the catheter hub the equipment for parenteral nutrition should be changed
contributes substantially to intraluminal colonization of every 24 hours, always swabbing the connections and taps
long-term catheters. Occasionally, catheters might become of the catheter with 10% concentration of alcohol before
hematogenously seeded from another focus of infection. handling them.2.6.11.15
Rarely, infusate contamination leads to CRBSI.1.16 Adverse events in central catheters were frequent
Important pathogenic determinants of catheter-related in neonatal populations, both for PICCs and in UVCs.
infection are 1) the material of which the device is made and 2) The most prevalent adverse event in PICCs was catheter
the intrinsic virulence factors of the infecting organism.8.9.11 occlusion, while clinical sepsis prevailed in UVCs.8.21
In vitro studies demonstrate that catheters made of PICCs presented a higher frequency of mechanical
polyvinyl chloride or polyethylene are likely less resistant adverse events, especially catheter occlusion and rupture.
to the adherence of microorganisms than are catheters However, its use presented very low rates of catheter-
made of Teflon, silicone elastomer, or polyurethane.9.13.15 related infections; these rates are similar or less than those
Some catheter materials also have surface irregularities reported in the literature.20 Therefore, we assert that PICC
that enhance the microbial adherence of certain species is a safe means for parenteral administration in the neonatal
(eg, coagulase-negative staphylococci, Acinetobacter population due to the low risk of infection found in this
calcoaceticus, and Pseudomonas aeruginosa); catheters study and in the literature. The use of UVCs resulted in
made of these materials are especially vulnerable to microbial a lower rate of mechanical adverse events: occlusions
colonization and subsequent infection.4.7.8 Additionally, or ruptures were not found in this catheter in this study.
certain catheter materials are more thrombogenic than However, the rates of infectious adverse events related to
others, a characteristic that also might predispose to catheter this catheter are the most prevalent.20.21
colonization and catheter-related infection. This association Several limitations should be considered when
has led to emphasis on preventing catheter-related thrombus interpreting our data. We conducted the study on a large
as an additional mechanism for reducing CRBSI.17 cohort of patients over a 3-year period, because our unit has
One study reports that the incident rate of PICC related low incidence of CLA-BSI. Several confounding factors
sepsis is between 2 and 21%. This study suggests that the still persist in this study. Underlying disease, duration of
lower incidence of infection in PICCs, when compared to mechanical ventilator, nosocomial infection were the risk
other UVCs, might be related to the low concentration of of sepsis in premature babies with UVCs.
bacteria in peripheral areas (50 to 100 colonies of bacteria
per cm2 of skin) when compared to the thorax (1,000 to
10,000 colonies of bacteria per cm2 of skin).18 CONCLUSIONS
The literature shows that there are microorganisms more
prevalent in catheter-related primary sepsis. The gram- The catheter duration have no significant difference
positive cocci are responsible for 65% of infections, while in risk of sepsis in premature babies with Umbilical Vein
the most prevalent are the Staphylococcus epidermidis Catheters. Burkholderia cepacia and Klebsiella pneumonia
(31%) and the Staphylococcus aureus (14%). The gram- mostly appeared in blood culture performance. 25% of UVC
negative bacilli account for 30% of infections and the most culture performance shows Pseudomonas aeroginosa.
14 Indonesian Journal of Tropical and Infectious Disease, Vol. 3. No. 1 January–March 2012: 10−14

REFERENCES 11. Mermel LA, Allon M, Bouza E. Clinical practice guidelines for the
diagnosis and management of intravascular catheter- related infection:
1. Franceschi AT, Cunha LC. Adverse Events Related to the Use of 2009 update by the Infec- tious Diseases Society of America. Clin
Central Venous Catheters in Hospitalized Newborns. Rev. Latino- Infect Dis. 2009; 49(1): 1–45.
Am. 2010; 18(2): 196–202. 12. Rubinson L, Diette GB. Best practices for insertion of central
2. O'Hara MB, Buzzard CJ, Reubens L, McDermott MP, DiGrazio W venous catheters in intensive-care units to prevent catheter- related
et.al. A Randomized Trial Comparing Long-term and Short-term bloodstream infections. J Lab Clin Med. 2004; 143(1): 5–13.
Use of Umbilical Venous Catheters in Premature Infants With 13. Kitterman JA, Phibbs RH, Tooley WH. Catheterization of umbilical
Birth Weights of Less Than 1251 Grams. Pediatrics. 2006; 118(1): vessels in newborn infants. Pediatr Clin North Am. 1970; 17:
e25–5. 895–912.
3. Verheij GH, Pas AB, Witlox RS, Wintjens VE, Walther FJ, and 14. Johns AW, Kitchen WH, Leslie DW. Complications of umbilical
Lopriore E. Poor Accuracy of Methods Currently Used to Determine vessel catheters. Med J Aust. 1972; 2(15): 810–15.
Umbilical Catheter Insertion Length. Int J Pediatr. 2010; 102(4): 15. Mer M, Duse AG, Galpin JS, Richards GA. Central venous
1–6. catheterization: a prospective, randomized, double blind study. Clin
4. O'Grady NP, Alexander M, Dellinger EP, Gerberding JL, Heard SO, Appl Thromb Hemost. 2009; 15(1): 19–26.
Maki D et.al. Guidelines for the Prevention of Intravascular Catheter- 16. Mahieu LM, De Muynck AO, Leven MM, De Dooy JJ, Goossens HJ,
Related Infections. Pediatrics 2002; 110(5): e51–74. Van Reempts PJ. Risk factors for central vascular catheter- associated
5. Sengupta A, Lehmann C, West MD, Perl TM, Milstone AM. Catheter bloodstream infections among patients in a neonatal intensive care
Duration and Risk of CLA-BSI in Neonates With PICCs Pediatrics. unit. J Hosp Infect. 2001; 48(2): 108–16.
2010; 125: 648–53. 17. Safdar N, Maki DG. Risk of catheter-related bloodstream infection
6. Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz with peripherally in- serted central venous catheters used in
RA et.al. Late-Onset Sepsis in Very Low Birth Weight Neonates: The hospitalized patients. Chest. 2005; 128(2): 489–95.
Experience of the NICHD Neonatal Research Network Pediatrics. 18. Ramritu P, Halton K, Cook D, Whitby M, Graves N. Catheter-related
2002; 110: 285–94. bloodstream infections in intensive care units: a systematic review
7. Zahedpasha, Kacho MA, Hajiahmadi M, Haghshenas M. Procalcitonin with meta-analysis. J Adv Nurs. 2008; 62(1): 3–21.
as a Marker of Neonatal Sepsis. Iran J Pediatr. 2009; 19(2): 117– 19. Eyer S, Brummitt C, Crossley K, Siegel R, Cerra F. Catheter-related
22. sepsis: prospective, randomized study of three methods of long-term
8. Khilnani P, Deopujari S, Carcillo J. Recent Advances in Sepsis and catheter maintenance. Crit Care Med. 1990; 18(10): 1073–9.
Septic Shock. Indian J Pediatr. 2008; 75 (8): 821–30. 20. Linares J, Sitges-Serra A, Garau J, Perez JL, Martin R. Pathogenesis
9. Pereira SM, Cardoso MH, Figuexeds AL, Mattos H, Rozembaum R, of catheter sepsis: a prospective study with quantitative and semi
Ferreira VI, Portinho MA et al. Sepsis-Related Mortality of Very Low quantitative cultures of catheter hub and segments. J Clin Microbiol.
Birth Weight Brazilian Infants: The Role of Pseudomonas aeruginosa. 1985; 21: 357–60.
Int J Pediatr. 2009; 6(2): 28–36. 21. Cronin WA, Germanson TP, Donowitz LG. Intravascular catheter
10. Tiffany K, Burke B, Odoms C, Oelberg DG. Current Practice colonization and related bloodstream infection in critically ill
Regarding the Enteral Feeding of High-Risk Newborns With neonates. Infect Control Hosp Epidemiol. 1990; 11: 301–8.
Umbilical Catheters In Situ. Pediatrics 2003; 112(1): 20–6.