Published online April 7, 2008
PEDIATRICS (doi:10.1542/peds.2007-1962)
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ARTICLE

Percutaneously Inserted Central Catheter for Total Parenteral Nutrition in Neonates: Complications Rates Related to Upper Versus Lower Extremity Insertion

Viet Hoang, MD, PharmDa, Jack Sills, MDa, Michelle Chandler, MDb, Erin Busalani, BSa, Robin Clifton-Koeppel, MS, RNC, CPNPa and Houchang D. Modanlou, MDa

a Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of California, School of Medicine, Irvine, California
b Division of Pediatric Radiology, Department of Radiology, University of California, School of Medicine, Irvine, California


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVE. The objective of this study was to compare the complication rates of upper versus lower extremity percutaneously inserted central catheters used for total parenteral nutrition in neonates.

METHODS. During a 48-month study period, 396 neonates were identified as having had percutaneously inserted central venous catheters. A total of 370 catheters were inserted from the upper and 107 from the lower extremity. Data retrieved and analyzed were birth weight, gestational age, age at placement, duration in place, duration of total parenteral nutrition, type of infusates, catheter-related bloodstream infection, phlebitis, leakage, occlusion, necrotizing enterocolitis, intraventricular hemorrhage, serum creatinine, liver function tests, and length of hospitalization.

RESULTS. The median birth weight and gestational age were 940 g and 28 weeks. The rate of catheter-related bloodstream infection was 11.6% for the upper and 9.3% in the lower extremity catheters. The most common organism was coagulase-negative Staphylococcus for both upper and lower extremity catheters and significantly higher with catheters from the upper extremity. Lower extremity catheters were in place longer, and the time from insertion to complication was also longer. The rate of cholestasis was higher for the upper extremity catheters. Multiple regression analysis showed that the most significant contributor to cholestasis was duration of time the catheters were in place and the duration of total parenteral nutrition administration. Receiver operating characteristics curve demonstrated higher sensitivity for duration of catheters in predicting cholestasis with duration of total parenteral nutrition being more specific.

CONCLUSION. Lower extremity percutaneously inserted central venous catheters had lower rates of catheter-related bloodstream infection, longer time to first complication, and lower cholestasis despite longer duration of total parenteral nutrition. When possible, lower extremity inserted catheters should be used for the administration of total parenteral nutrition.

Key Words: PICC • CRBSI • septicemia • TPN • cholestasis

Abbreviations: TPN—total parenteral nutrition • PICC—percutaneously inserted central catheter • CRBSI—catheter-related bloodstream infection


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Since the introduction of total parenteral nutrition (TPN) in the 1960s1 and use in ill neonates in the 1970s,2 central venous access has become important to effectuate fluid and nutritional requirements while gastrointestinal tracts are temporarily inadequate. Percutaneously inserted central catheters (PICCs) offer a discernible route for central venous access via cannulation of a peripheral vein in either the upper or the lower extremity. PICCs have become a requisite instrument to deliver hyperosmolar solutions, medications, and TPN over a prolonged dwell time.

Currently, the strategy of where PICCs are placed within the upper or lower extremity is based on finding a suitable peripheral vein for cannulation rather than which extremity offers less complication. Reported complications of PICCs including thrombosis, infection, catheter occlusion, phlebitis, renal insufficiency, and pulmonary complications are scarce in regard to characterizing the probable differences in complications in upper extremity versus lower extremity PICCs. Moreover, the role of central PICCs compared with noncentral PICCs in the efficacy and safety profile has been questioned.3 Nevertheless, the consensus is that PICCs offer better risk–benefit ratio, and as a result, we compare only central lines in either extremity.

The primary outcome of the study set forth was to look at the complication rates of PICCs in the upper versus lower extremity in terms of infection, catheter occlusion, phlebitis, liver dysfunction, renal insufficiency, and pulmonary complications. We hypothesized that PICCs placed either in the upper extremity or lower extremity have no differences in complication rates.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Study Population
This study was conducted at a 30-bed, tertiary-level NICU of a university teaching hospital. The study was approved by our institutional review board, and informed consent was waived. Data were aggregated retrospectively from a neonatal database over a 48-month interval from June 2002 to June 2006. A total of 495 PICC were placed during this study period. Neonates with liver dysfunction and inborn errors of metabolism were excluded. Liver dysfunction was defined as direct hyperbilirubinemia (serum direct bilirubin of >2.0 mg/dL) and high alanine aminotransferase and alanine aminotransferase levels. Of the 495 PICCs placed, 18 (4.3%) neonates were excluded, leaving 477 PICCs in 396 neonates. Sixteen were excluded secondary to liver dysfunction before PICC placement and 2 for inborn errors of metabolism. Total of 370 PICCs were placed in the upper and 107 in the lower extremity.

PICC Placement
At our institution, PICCs are placed by specialized nursing teams supervised by the neonatologists. Site selection for insertion of PICCs includes the antecubital fossa and greater and lesser saphenous veins.4 Because the antecubital fossa is considered to be less colonized, oily, and moist, upper extremity PICCs are used before lower extremity veins.5,6 Lower extremity PICCs were inserted because of failure to insert PICCs in the upper extremity, or it was the primary selection site. No patient had 2 PICCs at the same time. Only 2 French Silastic catheters (L-CATH Peel Away System, Becton Dickinson Infusion Therapy Systems, Inc, Sandy, UT) are used at our institution. Indications for a PICC are determined by the attending neonatologists and include the need for parenteral nutrition with a dextrose concentration of >12.5%, continuous infusion of vesicant medications, therapies with variations in osmolarity or pH, and prolonged antibiotic therapy. No blood products were infused via PICCs, and heparin was routinely added. Before the insertion of a PICC, informed consent was obtained. Dwell time and removal of the PICC depended on factors related to the patient's clinical condition and available vascular access related to ongoing patient care. Care of PICCs was performed by our nursing staff with outcome monitoring documented on a procedural logbook kept in the NICU. Upper extremity PICCs were considered as central when the tips resided in the superior vena cava before the right atrium. For low extremity PICCs, the tips were in high inferior vena cava at or above T10. They were considered noncentral when PICCs tips were located elsewhere.7–9 Removal of PICCs was accomplished because of complication, prolonged administration of TPN was not required, or feedings were advanced enough that supplemental fluids could be given by peripheral veins.

Definitions
Confirmation of catheter colonization and catheter-related bloodstream infection (CRBSI) was accomplished following Centers for Disease Control and Prevention guidelines.10 CRBSI is defined as a positive culture of an intravascular catheter with the same species as from ≥1 peripheral blood cultures. For culture, ≥1.0 mL of blood was procured from both a peripheral site and the central lines.11,12 A specialized team consisting of a neonatologist, a nurse epidemiologist, and a clinical nurse specialist provided surveillance for the occurrences of infection in our NICU, including those related to PICCs, because this strategy can reduce the rate of nosocomial infections.13,14 Phlebitis was defined as a physicochemical or mechanical complication not related to a proven infection. Cholestasis and renal insufficiency were defined by elevated direct bilirubin ≥2 mg/dL and maximum serum creatinine level of ≥1.6 mg/dL, respectively. Catheter occlusion was defined as pump occlusion or inability to flush and/or withdraw from the PICC and the cause to be related to thrombotic event. Leakage was construed as fluid extravasation and/or pleural or pericardial effusion. Mechanical complications were determined whenever dislodgement of a PICC occurred. Time to complication was defined as the number of days until 1 of the following complications occurred: phlebitis, occlusion, leakage, mechanical problem, or septicemia.

Statistical Methods
Data analysis was performed by using SAS 9.1 and SAS JMP 6 (SAS Institute Inc, Cary, NC). Nonparametric analysis, {chi}2 test, and Fisher's exact test were used for categorical data, and Wilcoxon/Kruskal-Wallis test was used for continuous variable. P < .05 was considered significant. Multiple logistic regression analysis was used to adjust for the patient's gestational age, gender, and catheter duration to compare the risk for complications.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Clinical Characteristics
The median gestational age and birth weight were 28 weeks (25.5–30.0) and 937 g (760.0–1359.5) and 28 weeks (25–31) and 946 g (740–1427) for the upper and lower extremities, respectively (Table 1). There was a slight predominance of male gender in both the upper and lower extremity groups. PICCs were placed on average day of life 6 (3–12) for the upper and day of life 8 (3–20) for the lower extremity. When the duration of PICC placement was analyzed, the lower extremity PICCs were indwelling significantly longer (P < .004) as compared with the upper extremity group. The median duration of TPN was 27 days (16–48) for the upper and 33 days (19.25–43.5) for the lower extremity, but the medians were not statistically significant. Both upper and lower extremity groups had a median (interquartile range) of 1 (1–2) PICC placed. Lower extremity PICCs were indwelling for longer periods of time before time to first complication, at a median of 15 days for the lower versus 9 days for the upper extremity. This difference did not reach statistical significance. Using logistic analysis, as the numbers of PICCs were used, it did not contribute to the increasing risk for complications (data not shown).


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  		TABLE 1 Demographic of Patients With PICCs From the Upper and Lower Extremities

 
Clinical Outcomes
The occurrence of adverse events was generally higher for the upper extremity placed PICCs (Table 2). CRBSI was the most frequently occurring life-threatening complication. Although the overall rate of CRBSI was not different between the 2 groups, the incidence of the most common nosocomial infection, coagulase-negative Staphylococcus, was significantly higher (P < .05) with upper extremity PICCs. Our rates of complication fell between the known reported rates of CRBSI.14–34 Similarly, the rate of diagnosis for cholestasis was significantly higher (P < .05) for the upper compared with the lower extremity PICCs. Occlusion and phlebitis were the most common complications noted. Similar to a previous report,35 phlebitis was not associated with septicemia in the lower or the upper extremity groups (P = .45 and P = .49, respectively). There were 3 pleural effusions from the upper extremity group and 1 from the lower extremity group. The pleural effusions were considered potentially life-threatening because they required thoracentesis. There was no incidence of pericardial effusion noted as a complication. The overall rates of leakage were similar in both groups. There were also no differences in maximum serum creatinine between the groups. Last, the median length of hospitalization and survival were not statistically different between the upper and lower extremity PICC groups (Table 1).


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  		TABLE 2 Types and Rates of Complications With Upper and Lower Extremity PICCs

 
Risk Factors Leading to CRBSI
As noted in Table 2, CRBSI was the most common complication noted in the study. There were a total of 8235 catheter days in both the upper and lower extremities: 6045 from the upper and 2190 from the lower extremity. The rate of CRBSI in the study was 11.6% (7.1 infections per 1000 catheter days) in the upper extremity and 9.3% (4.8 infections per 1000 catheter days) in the lower extremity (not statistically significant). Neonates with lower gestational age and birth weights had significantly higher rates of CRBSI in the upper extremity (P < .005 and P < .0001, respectively; Fig 1A and D). In contrast, lower extremity PICCs showed no statistical difference in gestational age and birth weight in neonates with and without CRBSI (Fig 1B and D). Neonates with CRBSI had an increased number of PICCs placed (P < .0001; Fig 1C). Time to CRBSI was longer in the lower extremity (14.5 days) as compared with 11 days in the upper; however, it did not reach statistical significance (P = .05; Fig 1A and B). Last, we examined the role of TPN with lipid emulsion and CRBSI. In the lower extremity, the duration of TPN administration was 34 and 32 days, respectively, with and without CRBSI (Fig 1A and B); however, in the upper extremity, the median duration of TPN use was 46 days as compared with 25 days without CRBSI (P < .0001; Fig 1A).


Figure 1
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  		FIGURE 1 A and B, Relationship between gestational age (weeks), duration of PICC (days), duration of TPN (days), and the incidence of septicemia in the upper extremity (A) and the lower extremity (B). C, Relationship between the median numbers of PICCs and the incidence of septicemia in the upper and lower extremities. D, Relationship between birth weight and the incidence of septicemia in the upper and lower extremity. a P < .0001. b P < .005.

 
Infusates
More than 96% of PICCs that were placed had TPN as an infusate, including lipids (Table 3). We considered infusates with extremes of pH, <6 or >8, and when they were statistically different between the upper and lower extremity groups. Within this category, there are some that we identified for study: vancomycin (pH: <4), phenobarbital (pH: 8.5–10.5), and doxapram (pH: 3.5–5.5). The administration of Vancomycin and phenobarbital was similar in both groups; however, doxapram was used more often in the lower extremity (P < .001). Furthermore, we looked at the effect of vasopressors and hydrocortisone use related to the rate of complications. Dopamine and dobutamine were used more often in the lower extremity (P < .005), whereas hydrocortisone use was similar in both groups.


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  		TABLE 3 Percentage of Patients and Type of Infusates Administered Through PICCs

 
Risk Factors Leading to Cholestasis
Neonates with lower gestational age and birth weight had statistically higher rates of cholestasis in the upper extremity (P < .005 and P < .0001, respectively; Fig 2A and D). There was no such association seen in the lower extremity (Fig 2A and B). Duration of TPN was significantly related to the development of cholestasis in both extremities (P < .001 for both; Fig 2A and B). Neonates with cholestasis had an increased number of PICCs placed (P < .0001; Fig 2C). The duration of PICCs in place was significant for the occurrence of cholestasis; however, this was observed only in the upper extremity (P < .0001; Fig 2A). For additional delineation of the roles of duration of PICCs versus TPN, a receiver operating characteristic curve was drawn (Fig 3). The duration of PICC use can predict cholestasis earlier than the duration of TPN administration. Between 20 and 30 days, the sensitivity (true-positive) of predicting cholestasis ranged from 0.5 to 0.9, respectively. Conversely, for the duration of TPN to reach the same sensitivity, it took 60 to 100 days. In the lower extremity, the duration of PICC was able to predict cholestasis quicker than the duration of TPN (Fig 4). Within the lower extremity, the range of PICC days was 20 to 90 days, signifying that the PICC was able to stay longer before sensitivity reached 0.9. These data are consistent with Table 1, in which the duration of PICC in place in the lower extremity was longer but had lower rates of cholestasis (Table 2).


Figure 2
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  		FIGURE 2 A and B, Relationship between gestational age (weeks), duration of PICC (days), duration of TPN (days), and the incidence of cholestasis in the upper extremity (A) and the lower extremity (B). C, Relationship between the median numbers of PICCs and the incidence of cholestasis in the upper and lower extremities. D, Relationship between birth weight and the incidence of cholestasis in the upper and lower extremity. P < .0001 and {Psi} P < .005.

 

Figure 3
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  		FIGURE 3 Receiver operator characteristic curve for upper extremity PICCs. A, Duration of PICC (days) and the sensitivity versus false-positive in predicting cholestasis. B, Duration of TPN (days) and the sensitivity versus false-positive in predicting cholestasis. Area under the curve = 0.85.

 

Figure 4
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  		FIGURE 4 Receiver operator characteristic curve for lower extremity PICCs. A, Duration of PICC (days) and the sensitivity versus false-positive in predicting cholestasis. B, Duration of TPN (days) and the sensitivity versus false-positive in predicting cholestasis. Area under the curve = 0.83.

 
Additional analysis of confounding variables leading to cholestasis was analyzed. Urinary tract infections, Gram-negative septicemia, CRBSI, and Gram-negative tracheal aspirates were statistically significant for contributing to cholestasis; however, this significance was not seen when upper and lower extremity groups were compared. Multivariate logistic analysis revealed that Gram-negative septicemia along with identification of a Gram-negative organism in the tracheal aspirate, duration of PICC in place, and duration of TPN had the most significant roles in contributing to cholestasis. Subsequent univariate analysis revealed that only the duration of TPN use was a significant contributor of cholestasis.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
This observational report represents the largest retrospective study of PICC-related rates of complications with 396 infants with a median gestational age of 28 weeks and birth weight of 940 g. We analyzed the complications rate between the upper and lower extremity inserted PICCs. Similar to findings of Freeman et al,36 decreasing birth weight, gestational age, and longer length of stay increased CRBSI. The occurrence of CRBSI and cholestasis was significantly higher with PICCs inserted from the upper extremities; therefore, we do not accept our hypothesis that placement of PICCs in either the upper extremity or the lower extremity has no difference in catheter-related complications.

CRBSI is the major cause of morbidity and mortality in NICU patients. The most common source is the skin flora contaminating either the catheter hub or the catheter itself. Janes et al37 conducted a prospective study of extremely low birth weight infants and reported complication rates of CRBSI at 28% incidence of first infection and 34% for first and subsequent infections; however, their definition of CRBSI was different from ours, leading to different rates of its occurrence. In our study, CRBSI was defined as a positive blood culture result from a PICC and a peripheral vessel, whereas the study by Janes et al37 defined CRBSI as any positive blood culture result without simultaneous peripheral vessel and PICC blood cultures. In another study of PICCs, Cairns et al32 also reported a higher rate of CRBSI of 31.1%. These significantly higher reported rates of septicemia may be in part attributable to a smaller sample size of 32 and 61 PICCs, respectively, as compared with 477 PICCs in our study. On additional analysis, we also found that although coagulase-negative Staphylococcus was the major organism in both the upper and lower extremity PICCs, lower extremity PICCs had a slightly higher prevalence of Gram-negative organisms causing septicemia.

The type of solutions being infused via PICCs may contribute to the complication rate. The pH and osmolarity of the infusate, possible contamination of infusate, and the rate of infusion are significant factors for the development of complications. For example, vancomycin, a commonly used antibiotic for staphylococcal infections in the NICU, is hyperosmolar with an extremely low pH (2.4).

The pathogenesis of cholestasis of the neonate is multifactorial. Processes in the development of cholestasis include increased bilirubin load from hemolysis, hepatocellular injury, septicemia-induced cholestasis, drugs such as penicillin/cephalosporins and sulfa-containing antibiotics, prolonged use of TPN, and decreased bile flow such as extrahepatic cholestasis from obstruction of the hepatic or common bile duct. The relationship between septicemia and cholestasis first described as pneumonia biliosa was reported as early as 1837.38 Septicemia-induced cholestasis, especially urinary tract infection and Gram-negative septicemia, in neonates has the highest association, although meningitis, omphalitis, and Gram-positive bacteria have also been reported.39–42 Similar to our findings, neonates with urinary tract infections, Gram-negative septicemia, and colonization of tracheal aspirate with Gram-negative bacteria statistically had higher rates of cholestasis, but when analyzed for the difference in extremities, they did not contribute to the higher rate of cholestasis seen with upper extremity PICCs; therefore, the cause of higher rates of cholestasis in the upper extremity must lie with another explanation.

In preterm infants between 32 and 36 weeks of gestation, a reduction in enterohepatic circulation of bile salts can lead to cholestasis by intestinal stasis and bacterial overgrowth with subsequent increase in lithocholic acid and impairment of bile flow.43 With Gram-negative septicemia, there is a decrease in bile secretion secondary to endotoxin production,44 hemolysis of red blood cells,45 and hepatic dysfunction secondary to decreased hepatic blood flow from hypotension or prolonged hypoxia. As a result, hepatic blood flow along with intestinal stasis and bacterial translocation can increase the risk for cholestasis. In animal studies, TPN has been known to impair intestinal mucosal immunity and acquiesce bacterial translocation, leading to an increased risk for cholestasis.46,47 There may be corroborating evidence in that although the duration of TPN correlates with the rate for cholestasis, the duration of PICCs had better sensitivity in predicting patients who were at risk for cholestasis as seen by the receiver operating characteristic curve.


   CONCLUSIONS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Upper extremity and lower extremity PICCs have statistically significant different rates of complications for coagulase-negative Staphylococcus septicemia and the rate of cholestasis, both of which were higher with the upper extremity PICCs. There was a slightly higher prevalence of Gram-negative CRBSI with lower extremity PICCs. PICCs inserted from the lower extremity remained functional for a longer period and had lower rate of overall complication compared with PICCs inserted from the upper extremity. When technically possible, use of PICCs inserted from the lower extremity should be considered for prolonged administration of TPN in ill neonates.


   FOOTNOTES
 
Accepted Sep 27, 2007.

Address correspondence to Houchang D. Modanlou, MD, Chief, Division of Neonatology; Director, Neonatal-Perinatal Medicine Fellowship Training Program. University of California, Irvine, 101 City Dr South, UCIMC, Building 56, Suite 600, Orange, CA 92868. E-mail: modanlou{at}uci.edu

This work was presented at the annual meeting of the American Academy of Pediatrics; October 26–30, 2007; San Francisco, CA.

The authors have indicated they have no financial relationships relevant to this article to disclose.


What's Known on This Subject

Uses of peripherally inserted central venous catheters in ill neonates, to administer total parenteral nutrition, are frequently associated with catheter-related bloodstream infection and other complications.

 

What This Study Adds

Lower extremity percutaneously inserted central venous catheters have lower rates of catheter-related bloodstream infection, longer time to first complication, and lower cholestasis despite longer duration of total parenteral nutrition.

 


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

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PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics




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