Research ArticleRisk Factors Related to Peripherally Inserted Central VenousCatheter Nonselective Removal in Neonates
Xiaohe Yu Shaojie Yue Mingjie Wang Chuanding Cao Zhengchang LiaoYing Ding Jia Huang andWen Li
Department of Paediatrics Xiangya Hospital of Central South University Changsha Hunan 410008 China
Correspondence should be addressed to Shaojie Yue shaojieyue163com
Received 28 November 2017 Revised 10 April 2018 Accepted 2 May 2018 Published 30 May 2018
Academic Editor Cem Kopuz
Copyright copy 2018 Xiaohe Yu et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited
We aimed to investigate the incidence and risk factors associated with nonselective removal of peripherally inserted central venouscatheter (PICC) in neonates In this prospective cohort study neonates who underwent PICC placement at neonatal intensive careunits (NICUs) in China from October 2012 to November 2015 were included The patient demographics catheter characteristicscatheter duration PICC insertion site indication for PICC insertion infuscate composition PICC tip location and cathetercomplications were recorded in a computerized database Risk factors for nonselective removal were analyzed A total of 497PICCs were placed in 496 neonates Nonselective removal occurred in 93 of PICCs during 10540 catheter-days (46 nonselectiveremovals per 1000 catheter-days) These included occlusion (3) infection (14) leakage (20) phlebitis (06) displacement(1) pleural effusion(06) and breaks (06) Noncentral tip position was independently associated with an increased risk ofnonselective removal (odds ratio 2621 95 confidence interval 1258-5461) after adjusting for gestational age sex birth weightand PICC dwell time No significant differences in the rate of complications occurred between silastic and polyurethane PICC ordifferent insertion sites Noncentral PICC tip position was the only independent risk factor for nonselective removal of PICC
1 Introduction
Peripherally inserted central catheters (PICCs) are routinelyused in term and preterm infants to provide intravenousaccess for prolonged therapy and parenteral nutrition [12] They are known to reduce the complications associatedwith the conventionally used central catheters PICCs canbe conveniently inserted at the bedside without the need forsurgical intervention They are essential in delivering life-saving treatment to neonates In particular PICCs representa large proportion of central lines inserted in the neonatalintensive care unit (NICU)
PICCs are associated with a reduced incidence of compli-cations such as thrombosis catheter occlusion and leakagecompared to short peripheral catheters [3] Despite theseadvantages PICCs are associated with various complicationssuch as occlusion infection thrombosis breakage migra-tion and displacement [4 5] which lead to nonselectiveremoval of the catheter Despite the studies illustratingthe advantages associated with PICC use short peripheral
catheters are vastly used in neonatal intensive care units(NICUs) for long-term intravenous therapies total parenteralnutrition and drug injection in Iran causing an increasedincidence of catheterization and complications which can beprevented by using PICCs [6] The daily risk of infection wasreported to be higher in PICCs in place for gt2 weeks thanPICCs thatwere used forlt2weeks [7] As these complicationsare associated with morbidity among neonates thereforeclinical data on nonselective removal may help in qualityimprovement efforts [8 9]
Previous studies have identified risk factors for compli-cations of PICCs in neonates These risk factors includedyoung age severity of illness catheter dwell time catheter tipposition and catheter insertion site [8 10ndash14] but reports inChinese neonates are rare Identifying modifiable risk factorsof complications is especially important as clinicians work toprevent catheter complications
Therefore in the present study we aimed to determine theassociation between patient and catheter characteristics andthe risk of nonselective removal in newborns
HindawiBioMed Research InternationalVolume 2018 Article ID 3769376 6 pageshttpsdoiorg10115520183769376
2 BioMed Research International
2 Methods
Between October 2012 and November 2015 496 consecutiveinfants who had been admitted to the 60-bed neonatal Inten-sive Care Unit (ICU) of Xiangya Central South University(China) and underwent insertion of a PICC were includedin the study Styptic was indicated for patients who requiredparenteral nutrition support for more than 1 week Informedconsent was obtained from the parents of all the infants priorto the start of the study
All PICCs were placed by a specialized team of nursesunder the supervision of pediatric interventional radiologistsThe upper limb approachwas preferred inmost cases becausethere are more veins available and the distance from thevena cava is shorter After PICC placement all catheter tippositions were determined by brief fluoroscopy Catheter tipswere defined as central at the time of placement if theywere in the superior vena cava (SVC) right atrium (RA)or high inferior vena cava (IVC) at or above the level ofthe diaphragm and as noncentral if located elsewhere ThePICCs were removed in the case of adverse events
Data regarding the patientrsquos age sex indications forcatheter insertion catheter characteristics catheter dura-tion infusate composition and catheter complications wereentered prospectively into a computerized database PICCinsertion sites were categorized into different blood vessels ofupper extremity lower extremity and head and neck
Silastic catheters (19 Fr BD USA) were exclusively usedduring the first two years of this study A total of 345silastic PICC lines were placed in the NICU but we stoppedusing these catheters because BD Biosciences stopped theproduction of the silastic catheters From October 2014onwards 152 polyurethane PICC lines of the same size (19Fr Medcomp USA) were used All PICCs were flushed usingheparin sodium
Data regarding all nonselective removals were collectedfrom all the neonates The complications included leakage atthe PICC insertion site phlebitis (erythema swelling painor palpable cord) infection (positive blood and catheter tipcultures) catheter occlusion (inability to infuse or withdraw)and mechanical malfunction (catheter damage) Catheterswere removed after completion of therapy or in case of com-plications The primary outcome was defined as the presenceof complications leading to PICC nonelective removal Thetime at risk for complications was the PICC dwell timecalculated as the number of days between insertion andremoval of PICC
21 Statistical Analysis All analyses were performed usingthe SAS statistical software version 7 (SAS Institute IncCary NC) Nonnormally distributed continuous variableswere expressed as median (IQR) Categorical variables wereexpressed as frequencies For simple comparisons betweencentral and noncentral PICCs the chi-square test and Fisherrsquosexact test were used to analyze categorical data The non-parametric test was used for continuous variables Odds ratio(OR) was calculated using multiple logistic regression withadjustments for gestational age sex birth weight and PICCdwell time Statistical significance was defined as Plt005
3 Results
Between October 2012 and November 2015 data from atotal of 497 PICCs were analyzed from 496 patients Table 1presents the patient characteristics The mean gestational age(GA)was 310plusmn25weeks themean birthweightwas 1537plusmn523g There were 284 (573) males and 212 (427) femalesMost of the newborns were premature (467 942) The GAof 31 infants was le28 weeks 28-32 weeks for 312 patients32-37 weeks for 124 patients and gt37 weeks for 29 patientsExtremely low birth weight (ELBW) was defined as a birthweight of lt1000 g and very low birth weight (VLBW) wasdefined as a birth weight of lt1500 g Among the neonates inour study 48 were ELBW and 236 were weighed 1000-1499 g152 weighed 1500-2000 g and 57 weighed gt2000 g 2 have nobirth weight record
The catheters were inserted at a median (interquartilerange) age of 8 (1-60) days Parenteral nutrition was the mostcommon indication for PICC with the majority of infantsreceiving gt125 dextrose-based infusion (450 PICCs) 24infants received lt125 dextrose-based solutions and 23PICCs were placed exclusively for intravenous antibiotictherapy The majority of PICCs (410 825) were inserted inthe upper extremities (Table 2) The mean duration of PICCwas 18 days (range 0-74 days)
Of the 497 PICCs 413 (831) were centrally positioned(central group) 83 (168) were noncentrally positioned(noncentral group) and one had no record regarding itsposition There were no differences between the two groupsregarding GA birth weight patient classification side ofPICC insertion PICC insertion site and PICC material (allPgt005) There are more boys in the noncentral PICC group(675 vs 552 P=0039)The rates of nonselective removal(181 vs 75 P=0002) were higher in the noncentral groupcompared with the central group (Table 1)
Complications occurred in 93 of PICCs over a total of10540 catheter-days (46 complications per 1000 catheter-days) These included occlusion (3) infection (14)leakage (20) phlebitis (06) displacement (1) pleu-ral effusion(06) and breaks (06) Most of the PICCs(451 907) were removed electively on completion oftherapy while 46 PICCs (92) were removed due to oneof the abovementioned complications Of these 39 PICCswere removed secondary to noninfectious complicationsand 7 were removed for infection-related complications(Table 3)
There were no statistically significant differences betweenthe types of infusates administered to the central and non-central groups TPN was the most commonly used infusatein both groups No statistically significant differences wereobserved in the GA at insertion (weeks) birth weight andthe mean PICC duration between the central and noncentralgroups There were 31 complications involving 413 centrallypositioned catheters (75) and 15 complications among the83 noncentral catheters (181 P=0002)
The majority of PICCs (694) were silastic while 306of the PICCs were polyurethane During the study periodthere were three cases (06) of pleural effusion All threepatients had polyurethane PICCs for parenteral nutrition
BioMed Research International 3
Table 1 Comparison of infant characteristics and outcomes between central and noncentral tip position
Characteristics Central (n=413) Non-central (n=83) P valueGestational age at insertion (weeks) 310 (245400) 31 (262395) 0841Birth weight (g) 1445 (7005170) 1450 (6803980) 0716Sex n () 0039Boy 228 (552) 56 (675)Girl 185 (448) 27 (325)Patient classification n () 0441Medical 396 (959) 79 (940)Surgical 17 (41) 5 (60)PICC dwell time (days) 18 (274) 17 (163) 0148Side of PICC insertion n () 0577Right 385 (948) 78 (963)Left 21 (52) 3 (37)PICC insertion site n () 0234Upper limbs 336 (814) 73(880)Head and neck 7 (17) 2 (24)PICC material n () 0883Silastic 287 (695) 58 (69)Polyurethane 126 (305) 26 (30)Nonselective removal 31 (75) 15 (181) 0002
Table 2 Comparison of infant PICC insertion site between central and noncentral tip position
PICC insertion site n () Central (n=413) Non-central (n=83)Upper limbs 336 73
The unadjusted (univariate analyses Table 4) andadjusted (multivariate analysis adjusted for catheter dwelltime age insertion site indication for PICC insertionand noncentral tip position Table 5) risk factors for PICCcomplications showed an increased risk of complications for
noncentral PICCs compared to central PICCS (OR 262195 CI 1258-5461 P=001 Table 5)
4 Discussion
In the present study we aimed to characterize and identifythe risk factors for complications necessitating removal ofPICCs in neonates Our study findings indicated that non-centrally located PICCs were an independent risk factor fornonselective removal Despite reductions in the incidence ofnonselective removal further efforts are needed to preventPICC-associated complications in neonates
In previous studies premature birth severity of infantcondition PICC duration [7 15] tip position [10 16] andsite of PICC insertion [11ndash13] have been suggested to berisk factors of nonselective removal An increased rate ofcomplications has been documented with noncentral PICC
4 BioMed Research International
Table 4 Univariable logistic analysis for PICCs complications
OR 95CI pGestational age 0860 (07440994) 0041Birth weight lt1500 g 1291 (06902417) 0425Boy 0721 (03931324) 0292Surgery 1586 (04515577) 0472Left side 2063 (06736326) 0205Non-upper limbs insertion site 0485 (01691394) 0179Silastic 1447 (07142932) 0305PICC dwell time 0980 (09521009) 0174Non-central 2718 (13935303) 0003
Table 5 Multivariable logistic analysis for PICCs complications
OR 95CI pGestational age 0830 (06871003) 0053Birth weight lt1500 g 1030 (04362437) 0946Boy 0582 (02941154) 0121PICC dwell time 0979 (09481010) 0184Non-central tip position 2621 (12585461) 0010
tips Moreover factors such as small vessel size decreasedblood flow rate turbulent flow and endothelial injury areconsidered to contribute to these complications In our studyalthough noncentrally located PICCs represented a smallpercentage (167) of inserted PICCs They were more likelyto be removed secondary to a complication compared withPICCs with a central tip position
Previous studies have reported nonselective removal ratesranging 29-208 [17ndash20] The rates of complications in ourstudy are similar to those reported previously Despite thelower rates of complications associated with centrally locatedPICCs often it is not possible to achieve centrally locatedPICCs due to factors such as venospasm venous tortuosityand venous valves [19] There is no clear evidence in theliterature indicating the association of catheter tip positionand complication rates in pediatric PICCs Some pediatricstudies have found that PICCs placed in noncentral veinsprovided safe and reliable intravenous access [17] whereasothers have suggested that PICCs terminating in noncentralvenous positions have higher risks of complication [10 16 19]Nevertheless these studies cannot be easily compared dueto inconsistent definitions of central veins Some authorshave classified the subclavian vein as a central positionfor the catheter tip Most clinicians consider a PICC toterminate in a central vein if the tip is located in the IVCSVC or right atrial junction (RAJ) After adjusting for otherimportant predictors of PICC complications such as agecatheter dwell time PICC insertion site and indications forPICC insertion our findings are in linewith previous findingsthat a noncentral catheter tip position is associated withincreased rates of nonselective removal
Increased complication rates in noncentral PICCs espe-cially mechanical complications may be the result of a
combination of factors such as vessel size turbulence bloodflow rate and endothelial injury A cadaveric study of ELBWinfants revealed that the outer diameter of the subclavianveins was significantly smaller than the BC (mean diametersof 26 and 25 mm vs 33 and 40 mm for the right andleft respectively) [21] The outer diameter of vessels withthe catheter tip may be inversely related to the rate ofmechanical and infiltrative complications In another studythe researchers discouraged the insertion of PICC tips in sub-clavian veins in neonates because catheters located in theseveins had a higher rate of infiltration and mechanical com-plications and shorter time to complications [8] The resultsof the present study suggested that noncentral catheters werean independent risk factor for noninfectious complicationsTherefore noncentrally located PICCs should be used withcaution due to their increased risk of complication
Ong et al carried out a prospective randomized studyto compare the complications between polyurethane andsilicone PICCs [22] They randomly assigned 326 patients toa proximal valve polyurethane PICC or a distal valve siliconePICC Polyurethane PICCs were found to be more durablethan silicone PICCs with a significantly lower incidenceof complications (268 vs 479 Plt0001) particularlyphlebitis and catheter-related infections No hydrothoraxcomplications occurred in both groupsHydrothorax compli-cations have been reported to occur regardless of the size ormaterial of the PICC [23] Nevertheless Pezzati et al carriedout a retrospective study involving 280 PICCs in 258 pretermneonates and found that no pleural effusion or cardiactamponades occurred in the silastic PICC group (232280829) whereas there was one case of pleural effusion andfive of cardiac tamponades in the polyurethane PICC group(48280 171) Based on these results Pezzati et al suggestedthat silastic catheters are safer and should be preferred overpolyurethane ones [24] We found no significant differencesin the rate of total complications and catheter-related infec-tions between the two types of PICC catheters but there wasa significantly lower incidence of complications of occlusionphlebitis displacement and breakage and a higher incidenceof pleural effusion in polyurethane PICCs Among the infantswho received total parenteral nutrition via PICC threeinfants suffered from PICC-induced hydrothorax Pleuralfluid accumulation can occur due to SVC obstruction withobstruction of lymphatic drainage and erosion or perforation
BioMed Research International 5
of the catheter through the vein into the pleural space In ourexperience all the three neonates initially had polyurethanePICCs in their SVC but two of the PICCs came out dueto migration We suspect that as polyurethane PICCs arestiffer and less flexible than silastic catheters they can moreeasily damage the vascular wall when placed in the SVC dueto the curve of the aortic arch In addition similar to theprevious study we also suggest choosing silastic cathetersover polyurethane ones especially in the case of ELBWbabies If the use of a polyurethane catheter is unavoidable wewould recommend using the saphenous approach in order toavoid the aortic curve A large-scale prospective randomizedmulticenter study is required to evaluate the incidence ofpleural effusion and cardiac tamponades in these two typesof PICCs
This study has several limitations First this was anobservational study and is therefore vulnerable to bias Theline tip position was also not regularly monitored norwas thrombosis identified via ultrasound Secondly somecatheter infections may have been treated with antibioticswhile the PICC remained in place and these complicationsmay not have been captured Finally despite this beinga large cohort our findings may not be generalizable asthis was a single-center study Larger prospective studiesacross multiple centers are needed to clarify the relationshipbetween these possible risk factors and PICC complications
5 Conclusion
Our prospective cohort study identified that noncentralcatheter tip position was the only independent risk factor fornonselective removal of PICC Therefore Clinicians shouldensure that catheter tips reside in the RA IVC or SVC at orabove the level of the diaphragm in neonates
Conflicts of Interest
All authors declare that there are no conflicts of interestregarding the publication of this article
References
[1] S B Ainsworth andW McGuire ldquoPeripherally inserted centralcatheters vs peripheral cannulas for delivering parenteral nutri-tion in neonatesrdquo Journal of the American Medical Associationvol 315 no 23 pp 2612-2613 2016
[2] C N Litz J G Tropf P D Danielson andNM Chandler ldquoTheidle central venous catheter in the NICU When should it beremovedrdquo Journal of Pediatric Surgery 2017
[3] M Legemaat P J Carr R M Van Rens M Van Dijk I EPoslawsky and A Van den Hoogen ldquoPeripheral intravenouscannulation Complication rates in the neonatal population Amulticenter observational studyrdquo Journal of Vascular Access vol17 no 4 pp 360ndash365 2016
[4] A S McCay E C Elliott and M Walden ldquoVideos in clinicalmedicine PICC placement in the neonaterdquo The New EnglandJournal of Medicine vol 370 no 11 p e17 2014
[5] M-Y Hei X-C Zhang X-Y Gao et al ldquoCatheter-relatedinfection and pathogens of umbilical venous catheterization in
a neonatal intensive care unit in Chinardquo American Journal ofPerinatology vol 29 no 2 pp 107ndash114 2012
[6] F Soroush A Zargham-Boroujeni and M Namnabati ldquoTherelationship between nurses1015840 clinical competence and burnoutin neonatal intensive care unitsrdquo Iranian Journal of Nursing andMidwifery Research vol 21 no 4 p 424 2016
[7] A M Milstone N G Reich S Advani et al ldquoCatheter dwelltime and clabsis in neonates with piccs A multicenter cohortstudyrdquo Pediatrics vol 132 no 6 pp e1609ndashe1615 2013
[8] A Jain P Deshpande and P Shah ldquoPeripherally insertedcentral catheter tip position and risk of associated complicationsin neonatesrdquo Journal of Perinatology vol 33 no 4 pp 307ndash3122013
[9] V Chopra D Ratz L Kuhn T Lopus C Chenoweth andS Krein ldquoPICC-associated bloodstream infections Prevalencepatterns and predictorsrdquoAmerican Journal ofMedicine vol 127no 4 pp 319ndash328 2014
[10] J M Racadio D A Doellman N D Johnson J A Bean andB R Jacobs ldquoPediatric peripherally inserted central catheterscomplication rates related to catheter tip locationrdquo Pediatricsvol 107 no 2 p E28 2001
[11] P Kisa J Ting A Callejas H Osiovich and S A ButterworthldquoMajor thrombotic complications with lower limb PICCs insurgical neonatesrdquo Journal of Pediatric Surgery vol 50 no 5pp 786ndash789 2015
[12] V Hoang J Sills M Chandler E Busalani R Clifton-Koeppeland H D Modanlou ldquoPercutaneously inserted central catheterfor total parenteral nutrition in neonates Complications ratesrelated to upper versus lower extremity insertionrdquo Pediatricsvol 121 no 5 pp e1152ndashe1159 2008
[13] P Panagiotounakou G Antonogeorgos E Gounari SPapadakis J Labadaridis and A K Gounaris ldquoPeripherallyinserted central venous catheters Frequency of complicationsin premature newborn depends on the insertion siterdquo Journalof Perinatology vol 34 no 6 pp 461ndash463 2014
[14] X Li H Wang Y Chen and Z Yuan ldquoMultifactor analysisof malposition of peripherally inserted central catheters inpatients with cancerrdquo Clinical Journal of Oncology Nursing vol19 no 4 pp E70ndashE73 2015
[15] I Njere S Islam D Parish J Kuna and A S KeshtgarldquoOutcome of peripherally inserted central venous catheters insurgical andmedical neonatesrdquo Journal of Pediatric Surgery vol46 no 5 pp 946ndash950 2011
[16] K Colacchio Y Deng V Northrup and M J BizzarroldquoComplications associated with central and non-central venouscatheters in a neonatal intensive care unitrdquo Journal of Perinatol-ogy vol 32 no 12 pp 941ndash946 2012
[17] Y Ohki K Maruyama A Harigaya M Kohno and HArakawa ldquoComplications of peripherally inserted centralvenous catheter in Japanese neonatal intensive care unitsrdquoPediatrics International vol 55 no 2 pp 185ndash189 2013
[18] D W Cartwright ldquoCentral venous lines in neonates A study of2186 cathetersrdquoADC - Fetal and Neonatal Edition vol 89 no 6pp F504ndashF508 2004
[19] K Jumani S Advani N G Reich L Gosey andAMMilstoneldquoRisk factors for peripherally inserted central venous cathetercomplications in childrenrdquo JAMA Pediatrics vol 167 no 5 pp429ndash435 2013
[20] J Moran C Y Colbert J Song et al ldquoScreening for novelrisk factors related to peripherally inserted central catheter-associated complicationsrdquo Journal of Hospital Medicine vol 9no 8 pp 481ndash489 2014
6 BioMed Research International
[21] F Eifinger K Brisken B Roth and J Koebke ldquoTopographicalanatomyof central venous system in extremely low-birthweightneonates less than 1000 grams and the effect of central venouscatheter placementrdquoClinical Anatomy vol 24 no 6 pp 711ndash7162011
[22] C K Ong S K Venkatesh G B Lau and S CWang ldquoProspec-tive randomized comparative evaluation of proximal valvepolyurethane and distal valve silicone peripherally inserted cen-tral cathetersrdquo Journal of Vascular and Interventional Radiologyvol 21 no 8 pp 1191ndash1196 2010
[23] J A Leipala J Petaja and V Fellman ldquoPerforation compli-cations of percutaneous central venous catheters in very lowbirthweight infantsrdquo Journal of Paediatrics andChildHealth vol37 no 2 pp 168ndash171 2001
[24] M Pezzati L Filippi G Chiti et al ldquoCentral venous cathetersand cardiac tamponade in preterm infantsrdquo Intensive CareMedicine vol 30 no 12 pp 2253ndash2256 2004
Computational and Mathematical Methods in Medicine
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Submit your manuscripts atwwwhindawicom
2 BioMed Research International
2 Methods
Between October 2012 and November 2015 496 consecutiveinfants who had been admitted to the 60-bed neonatal Inten-sive Care Unit (ICU) of Xiangya Central South University(China) and underwent insertion of a PICC were includedin the study Styptic was indicated for patients who requiredparenteral nutrition support for more than 1 week Informedconsent was obtained from the parents of all the infants priorto the start of the study
All PICCs were placed by a specialized team of nursesunder the supervision of pediatric interventional radiologistsThe upper limb approachwas preferred inmost cases becausethere are more veins available and the distance from thevena cava is shorter After PICC placement all catheter tippositions were determined by brief fluoroscopy Catheter tipswere defined as central at the time of placement if theywere in the superior vena cava (SVC) right atrium (RA)or high inferior vena cava (IVC) at or above the level ofthe diaphragm and as noncentral if located elsewhere ThePICCs were removed in the case of adverse events
Data regarding the patientrsquos age sex indications forcatheter insertion catheter characteristics catheter dura-tion infusate composition and catheter complications wereentered prospectively into a computerized database PICCinsertion sites were categorized into different blood vessels ofupper extremity lower extremity and head and neck
Silastic catheters (19 Fr BD USA) were exclusively usedduring the first two years of this study A total of 345silastic PICC lines were placed in the NICU but we stoppedusing these catheters because BD Biosciences stopped theproduction of the silastic catheters From October 2014onwards 152 polyurethane PICC lines of the same size (19Fr Medcomp USA) were used All PICCs were flushed usingheparin sodium
Data regarding all nonselective removals were collectedfrom all the neonates The complications included leakage atthe PICC insertion site phlebitis (erythema swelling painor palpable cord) infection (positive blood and catheter tipcultures) catheter occlusion (inability to infuse or withdraw)and mechanical malfunction (catheter damage) Catheterswere removed after completion of therapy or in case of com-plications The primary outcome was defined as the presenceof complications leading to PICC nonelective removal Thetime at risk for complications was the PICC dwell timecalculated as the number of days between insertion andremoval of PICC
21 Statistical Analysis All analyses were performed usingthe SAS statistical software version 7 (SAS Institute IncCary NC) Nonnormally distributed continuous variableswere expressed as median (IQR) Categorical variables wereexpressed as frequencies For simple comparisons betweencentral and noncentral PICCs the chi-square test and Fisherrsquosexact test were used to analyze categorical data The non-parametric test was used for continuous variables Odds ratio(OR) was calculated using multiple logistic regression withadjustments for gestational age sex birth weight and PICCdwell time Statistical significance was defined as Plt005
3 Results
Between October 2012 and November 2015 data from atotal of 497 PICCs were analyzed from 496 patients Table 1presents the patient characteristics The mean gestational age(GA)was 310plusmn25weeks themean birthweightwas 1537plusmn523g There were 284 (573) males and 212 (427) femalesMost of the newborns were premature (467 942) The GAof 31 infants was le28 weeks 28-32 weeks for 312 patients32-37 weeks for 124 patients and gt37 weeks for 29 patientsExtremely low birth weight (ELBW) was defined as a birthweight of lt1000 g and very low birth weight (VLBW) wasdefined as a birth weight of lt1500 g Among the neonates inour study 48 were ELBW and 236 were weighed 1000-1499 g152 weighed 1500-2000 g and 57 weighed gt2000 g 2 have nobirth weight record
The catheters were inserted at a median (interquartilerange) age of 8 (1-60) days Parenteral nutrition was the mostcommon indication for PICC with the majority of infantsreceiving gt125 dextrose-based infusion (450 PICCs) 24infants received lt125 dextrose-based solutions and 23PICCs were placed exclusively for intravenous antibiotictherapy The majority of PICCs (410 825) were inserted inthe upper extremities (Table 2) The mean duration of PICCwas 18 days (range 0-74 days)
Of the 497 PICCs 413 (831) were centrally positioned(central group) 83 (168) were noncentrally positioned(noncentral group) and one had no record regarding itsposition There were no differences between the two groupsregarding GA birth weight patient classification side ofPICC insertion PICC insertion site and PICC material (allPgt005) There are more boys in the noncentral PICC group(675 vs 552 P=0039)The rates of nonselective removal(181 vs 75 P=0002) were higher in the noncentral groupcompared with the central group (Table 1)
Complications occurred in 93 of PICCs over a total of10540 catheter-days (46 complications per 1000 catheter-days) These included occlusion (3) infection (14)leakage (20) phlebitis (06) displacement (1) pleu-ral effusion(06) and breaks (06) Most of the PICCs(451 907) were removed electively on completion oftherapy while 46 PICCs (92) were removed due to oneof the abovementioned complications Of these 39 PICCswere removed secondary to noninfectious complicationsand 7 were removed for infection-related complications(Table 3)
There were no statistically significant differences betweenthe types of infusates administered to the central and non-central groups TPN was the most commonly used infusatein both groups No statistically significant differences wereobserved in the GA at insertion (weeks) birth weight andthe mean PICC duration between the central and noncentralgroups There were 31 complications involving 413 centrallypositioned catheters (75) and 15 complications among the83 noncentral catheters (181 P=0002)
The majority of PICCs (694) were silastic while 306of the PICCs were polyurethane During the study periodthere were three cases (06) of pleural effusion All threepatients had polyurethane PICCs for parenteral nutrition
BioMed Research International 3
Table 1 Comparison of infant characteristics and outcomes between central and noncentral tip position
Characteristics Central (n=413) Non-central (n=83) P valueGestational age at insertion (weeks) 310 (245400) 31 (262395) 0841Birth weight (g) 1445 (7005170) 1450 (6803980) 0716Sex n () 0039Boy 228 (552) 56 (675)Girl 185 (448) 27 (325)Patient classification n () 0441Medical 396 (959) 79 (940)Surgical 17 (41) 5 (60)PICC dwell time (days) 18 (274) 17 (163) 0148Side of PICC insertion n () 0577Right 385 (948) 78 (963)Left 21 (52) 3 (37)PICC insertion site n () 0234Upper limbs 336 (814) 73(880)Head and neck 7 (17) 2 (24)PICC material n () 0883Silastic 287 (695) 58 (69)Polyurethane 126 (305) 26 (30)Nonselective removal 31 (75) 15 (181) 0002
Table 2 Comparison of infant PICC insertion site between central and noncentral tip position
PICC insertion site n () Central (n=413) Non-central (n=83)Upper limbs 336 73
The unadjusted (univariate analyses Table 4) andadjusted (multivariate analysis adjusted for catheter dwelltime age insertion site indication for PICC insertionand noncentral tip position Table 5) risk factors for PICCcomplications showed an increased risk of complications for
noncentral PICCs compared to central PICCS (OR 262195 CI 1258-5461 P=001 Table 5)
4 Discussion
In the present study we aimed to characterize and identifythe risk factors for complications necessitating removal ofPICCs in neonates Our study findings indicated that non-centrally located PICCs were an independent risk factor fornonselective removal Despite reductions in the incidence ofnonselective removal further efforts are needed to preventPICC-associated complications in neonates
In previous studies premature birth severity of infantcondition PICC duration [7 15] tip position [10 16] andsite of PICC insertion [11ndash13] have been suggested to berisk factors of nonselective removal An increased rate ofcomplications has been documented with noncentral PICC
4 BioMed Research International
Table 4 Univariable logistic analysis for PICCs complications
OR 95CI pGestational age 0860 (07440994) 0041Birth weight lt1500 g 1291 (06902417) 0425Boy 0721 (03931324) 0292Surgery 1586 (04515577) 0472Left side 2063 (06736326) 0205Non-upper limbs insertion site 0485 (01691394) 0179Silastic 1447 (07142932) 0305PICC dwell time 0980 (09521009) 0174Non-central 2718 (13935303) 0003
Table 5 Multivariable logistic analysis for PICCs complications
OR 95CI pGestational age 0830 (06871003) 0053Birth weight lt1500 g 1030 (04362437) 0946Boy 0582 (02941154) 0121PICC dwell time 0979 (09481010) 0184Non-central tip position 2621 (12585461) 0010
tips Moreover factors such as small vessel size decreasedblood flow rate turbulent flow and endothelial injury areconsidered to contribute to these complications In our studyalthough noncentrally located PICCs represented a smallpercentage (167) of inserted PICCs They were more likelyto be removed secondary to a complication compared withPICCs with a central tip position
Previous studies have reported nonselective removal ratesranging 29-208 [17ndash20] The rates of complications in ourstudy are similar to those reported previously Despite thelower rates of complications associated with centrally locatedPICCs often it is not possible to achieve centrally locatedPICCs due to factors such as venospasm venous tortuosityand venous valves [19] There is no clear evidence in theliterature indicating the association of catheter tip positionand complication rates in pediatric PICCs Some pediatricstudies have found that PICCs placed in noncentral veinsprovided safe and reliable intravenous access [17] whereasothers have suggested that PICCs terminating in noncentralvenous positions have higher risks of complication [10 16 19]Nevertheless these studies cannot be easily compared dueto inconsistent definitions of central veins Some authorshave classified the subclavian vein as a central positionfor the catheter tip Most clinicians consider a PICC toterminate in a central vein if the tip is located in the IVCSVC or right atrial junction (RAJ) After adjusting for otherimportant predictors of PICC complications such as agecatheter dwell time PICC insertion site and indications forPICC insertion our findings are in linewith previous findingsthat a noncentral catheter tip position is associated withincreased rates of nonselective removal
Increased complication rates in noncentral PICCs espe-cially mechanical complications may be the result of a
combination of factors such as vessel size turbulence bloodflow rate and endothelial injury A cadaveric study of ELBWinfants revealed that the outer diameter of the subclavianveins was significantly smaller than the BC (mean diametersof 26 and 25 mm vs 33 and 40 mm for the right andleft respectively) [21] The outer diameter of vessels withthe catheter tip may be inversely related to the rate ofmechanical and infiltrative complications In another studythe researchers discouraged the insertion of PICC tips in sub-clavian veins in neonates because catheters located in theseveins had a higher rate of infiltration and mechanical com-plications and shorter time to complications [8] The resultsof the present study suggested that noncentral catheters werean independent risk factor for noninfectious complicationsTherefore noncentrally located PICCs should be used withcaution due to their increased risk of complication
Ong et al carried out a prospective randomized studyto compare the complications between polyurethane andsilicone PICCs [22] They randomly assigned 326 patients toa proximal valve polyurethane PICC or a distal valve siliconePICC Polyurethane PICCs were found to be more durablethan silicone PICCs with a significantly lower incidenceof complications (268 vs 479 Plt0001) particularlyphlebitis and catheter-related infections No hydrothoraxcomplications occurred in both groupsHydrothorax compli-cations have been reported to occur regardless of the size ormaterial of the PICC [23] Nevertheless Pezzati et al carriedout a retrospective study involving 280 PICCs in 258 pretermneonates and found that no pleural effusion or cardiactamponades occurred in the silastic PICC group (232280829) whereas there was one case of pleural effusion andfive of cardiac tamponades in the polyurethane PICC group(48280 171) Based on these results Pezzati et al suggestedthat silastic catheters are safer and should be preferred overpolyurethane ones [24] We found no significant differencesin the rate of total complications and catheter-related infec-tions between the two types of PICC catheters but there wasa significantly lower incidence of complications of occlusionphlebitis displacement and breakage and a higher incidenceof pleural effusion in polyurethane PICCs Among the infantswho received total parenteral nutrition via PICC threeinfants suffered from PICC-induced hydrothorax Pleuralfluid accumulation can occur due to SVC obstruction withobstruction of lymphatic drainage and erosion or perforation
BioMed Research International 5
of the catheter through the vein into the pleural space In ourexperience all the three neonates initially had polyurethanePICCs in their SVC but two of the PICCs came out dueto migration We suspect that as polyurethane PICCs arestiffer and less flexible than silastic catheters they can moreeasily damage the vascular wall when placed in the SVC dueto the curve of the aortic arch In addition similar to theprevious study we also suggest choosing silastic cathetersover polyurethane ones especially in the case of ELBWbabies If the use of a polyurethane catheter is unavoidable wewould recommend using the saphenous approach in order toavoid the aortic curve A large-scale prospective randomizedmulticenter study is required to evaluate the incidence ofpleural effusion and cardiac tamponades in these two typesof PICCs
This study has several limitations First this was anobservational study and is therefore vulnerable to bias Theline tip position was also not regularly monitored norwas thrombosis identified via ultrasound Secondly somecatheter infections may have been treated with antibioticswhile the PICC remained in place and these complicationsmay not have been captured Finally despite this beinga large cohort our findings may not be generalizable asthis was a single-center study Larger prospective studiesacross multiple centers are needed to clarify the relationshipbetween these possible risk factors and PICC complications
5 Conclusion
Our prospective cohort study identified that noncentralcatheter tip position was the only independent risk factor fornonselective removal of PICC Therefore Clinicians shouldensure that catheter tips reside in the RA IVC or SVC at orabove the level of the diaphragm in neonates
Conflicts of Interest
All authors declare that there are no conflicts of interestregarding the publication of this article
References
[1] S B Ainsworth andW McGuire ldquoPeripherally inserted centralcatheters vs peripheral cannulas for delivering parenteral nutri-tion in neonatesrdquo Journal of the American Medical Associationvol 315 no 23 pp 2612-2613 2016
[2] C N Litz J G Tropf P D Danielson andNM Chandler ldquoTheidle central venous catheter in the NICU When should it beremovedrdquo Journal of Pediatric Surgery 2017
[3] M Legemaat P J Carr R M Van Rens M Van Dijk I EPoslawsky and A Van den Hoogen ldquoPeripheral intravenouscannulation Complication rates in the neonatal population Amulticenter observational studyrdquo Journal of Vascular Access vol17 no 4 pp 360ndash365 2016
[4] A S McCay E C Elliott and M Walden ldquoVideos in clinicalmedicine PICC placement in the neonaterdquo The New EnglandJournal of Medicine vol 370 no 11 p e17 2014
[5] M-Y Hei X-C Zhang X-Y Gao et al ldquoCatheter-relatedinfection and pathogens of umbilical venous catheterization in
a neonatal intensive care unit in Chinardquo American Journal ofPerinatology vol 29 no 2 pp 107ndash114 2012
[6] F Soroush A Zargham-Boroujeni and M Namnabati ldquoTherelationship between nurses1015840 clinical competence and burnoutin neonatal intensive care unitsrdquo Iranian Journal of Nursing andMidwifery Research vol 21 no 4 p 424 2016
[7] A M Milstone N G Reich S Advani et al ldquoCatheter dwelltime and clabsis in neonates with piccs A multicenter cohortstudyrdquo Pediatrics vol 132 no 6 pp e1609ndashe1615 2013
[8] A Jain P Deshpande and P Shah ldquoPeripherally insertedcentral catheter tip position and risk of associated complicationsin neonatesrdquo Journal of Perinatology vol 33 no 4 pp 307ndash3122013
[9] V Chopra D Ratz L Kuhn T Lopus C Chenoweth andS Krein ldquoPICC-associated bloodstream infections Prevalencepatterns and predictorsrdquoAmerican Journal ofMedicine vol 127no 4 pp 319ndash328 2014
[10] J M Racadio D A Doellman N D Johnson J A Bean andB R Jacobs ldquoPediatric peripherally inserted central catheterscomplication rates related to catheter tip locationrdquo Pediatricsvol 107 no 2 p E28 2001
[11] P Kisa J Ting A Callejas H Osiovich and S A ButterworthldquoMajor thrombotic complications with lower limb PICCs insurgical neonatesrdquo Journal of Pediatric Surgery vol 50 no 5pp 786ndash789 2015
[12] V Hoang J Sills M Chandler E Busalani R Clifton-Koeppeland H D Modanlou ldquoPercutaneously inserted central catheterfor total parenteral nutrition in neonates Complications ratesrelated to upper versus lower extremity insertionrdquo Pediatricsvol 121 no 5 pp e1152ndashe1159 2008
[13] P Panagiotounakou G Antonogeorgos E Gounari SPapadakis J Labadaridis and A K Gounaris ldquoPeripherallyinserted central venous catheters Frequency of complicationsin premature newborn depends on the insertion siterdquo Journalof Perinatology vol 34 no 6 pp 461ndash463 2014
[14] X Li H Wang Y Chen and Z Yuan ldquoMultifactor analysisof malposition of peripherally inserted central catheters inpatients with cancerrdquo Clinical Journal of Oncology Nursing vol19 no 4 pp E70ndashE73 2015
[15] I Njere S Islam D Parish J Kuna and A S KeshtgarldquoOutcome of peripherally inserted central venous catheters insurgical andmedical neonatesrdquo Journal of Pediatric Surgery vol46 no 5 pp 946ndash950 2011
[16] K Colacchio Y Deng V Northrup and M J BizzarroldquoComplications associated with central and non-central venouscatheters in a neonatal intensive care unitrdquo Journal of Perinatol-ogy vol 32 no 12 pp 941ndash946 2012
[17] Y Ohki K Maruyama A Harigaya M Kohno and HArakawa ldquoComplications of peripherally inserted centralvenous catheter in Japanese neonatal intensive care unitsrdquoPediatrics International vol 55 no 2 pp 185ndash189 2013
[18] D W Cartwright ldquoCentral venous lines in neonates A study of2186 cathetersrdquoADC - Fetal and Neonatal Edition vol 89 no 6pp F504ndashF508 2004
[19] K Jumani S Advani N G Reich L Gosey andAMMilstoneldquoRisk factors for peripherally inserted central venous cathetercomplications in childrenrdquo JAMA Pediatrics vol 167 no 5 pp429ndash435 2013
[20] J Moran C Y Colbert J Song et al ldquoScreening for novelrisk factors related to peripherally inserted central catheter-associated complicationsrdquo Journal of Hospital Medicine vol 9no 8 pp 481ndash489 2014
6 BioMed Research International
[21] F Eifinger K Brisken B Roth and J Koebke ldquoTopographicalanatomyof central venous system in extremely low-birthweightneonates less than 1000 grams and the effect of central venouscatheter placementrdquoClinical Anatomy vol 24 no 6 pp 711ndash7162011
[22] C K Ong S K Venkatesh G B Lau and S CWang ldquoProspec-tive randomized comparative evaluation of proximal valvepolyurethane and distal valve silicone peripherally inserted cen-tral cathetersrdquo Journal of Vascular and Interventional Radiologyvol 21 no 8 pp 1191ndash1196 2010
[23] J A Leipala J Petaja and V Fellman ldquoPerforation compli-cations of percutaneous central venous catheters in very lowbirthweight infantsrdquo Journal of Paediatrics andChildHealth vol37 no 2 pp 168ndash171 2001
[24] M Pezzati L Filippi G Chiti et al ldquoCentral venous cathetersand cardiac tamponade in preterm infantsrdquo Intensive CareMedicine vol 30 no 12 pp 2253ndash2256 2004
The unadjusted (univariate analyses Table 4) andadjusted (multivariate analysis adjusted for catheter dwelltime age insertion site indication for PICC insertionand noncentral tip position Table 5) risk factors for PICCcomplications showed an increased risk of complications for
noncentral PICCs compared to central PICCS (OR 262195 CI 1258-5461 P=001 Table 5)
4 Discussion
In the present study we aimed to characterize and identifythe risk factors for complications necessitating removal ofPICCs in neonates Our study findings indicated that non-centrally located PICCs were an independent risk factor fornonselective removal Despite reductions in the incidence ofnonselective removal further efforts are needed to preventPICC-associated complications in neonates
In previous studies premature birth severity of infantcondition PICC duration [7 15] tip position [10 16] andsite of PICC insertion [11ndash13] have been suggested to berisk factors of nonselective removal An increased rate ofcomplications has been documented with noncentral PICC
4 BioMed Research International
Table 4 Univariable logistic analysis for PICCs complications
OR 95CI pGestational age 0860 (07440994) 0041Birth weight lt1500 g 1291 (06902417) 0425Boy 0721 (03931324) 0292Surgery 1586 (04515577) 0472Left side 2063 (06736326) 0205Non-upper limbs insertion site 0485 (01691394) 0179Silastic 1447 (07142932) 0305PICC dwell time 0980 (09521009) 0174Non-central 2718 (13935303) 0003
Table 5 Multivariable logistic analysis for PICCs complications
OR 95CI pGestational age 0830 (06871003) 0053Birth weight lt1500 g 1030 (04362437) 0946Boy 0582 (02941154) 0121PICC dwell time 0979 (09481010) 0184Non-central tip position 2621 (12585461) 0010
tips Moreover factors such as small vessel size decreasedblood flow rate turbulent flow and endothelial injury areconsidered to contribute to these complications In our studyalthough noncentrally located PICCs represented a smallpercentage (167) of inserted PICCs They were more likelyto be removed secondary to a complication compared withPICCs with a central tip position
Previous studies have reported nonselective removal ratesranging 29-208 [17ndash20] The rates of complications in ourstudy are similar to those reported previously Despite thelower rates of complications associated with centrally locatedPICCs often it is not possible to achieve centrally locatedPICCs due to factors such as venospasm venous tortuosityand venous valves [19] There is no clear evidence in theliterature indicating the association of catheter tip positionand complication rates in pediatric PICCs Some pediatricstudies have found that PICCs placed in noncentral veinsprovided safe and reliable intravenous access [17] whereasothers have suggested that PICCs terminating in noncentralvenous positions have higher risks of complication [10 16 19]Nevertheless these studies cannot be easily compared dueto inconsistent definitions of central veins Some authorshave classified the subclavian vein as a central positionfor the catheter tip Most clinicians consider a PICC toterminate in a central vein if the tip is located in the IVCSVC or right atrial junction (RAJ) After adjusting for otherimportant predictors of PICC complications such as agecatheter dwell time PICC insertion site and indications forPICC insertion our findings are in linewith previous findingsthat a noncentral catheter tip position is associated withincreased rates of nonselective removal
Increased complication rates in noncentral PICCs espe-cially mechanical complications may be the result of a
combination of factors such as vessel size turbulence bloodflow rate and endothelial injury A cadaveric study of ELBWinfants revealed that the outer diameter of the subclavianveins was significantly smaller than the BC (mean diametersof 26 and 25 mm vs 33 and 40 mm for the right andleft respectively) [21] The outer diameter of vessels withthe catheter tip may be inversely related to the rate ofmechanical and infiltrative complications In another studythe researchers discouraged the insertion of PICC tips in sub-clavian veins in neonates because catheters located in theseveins had a higher rate of infiltration and mechanical com-plications and shorter time to complications [8] The resultsof the present study suggested that noncentral catheters werean independent risk factor for noninfectious complicationsTherefore noncentrally located PICCs should be used withcaution due to their increased risk of complication
Ong et al carried out a prospective randomized studyto compare the complications between polyurethane andsilicone PICCs [22] They randomly assigned 326 patients toa proximal valve polyurethane PICC or a distal valve siliconePICC Polyurethane PICCs were found to be more durablethan silicone PICCs with a significantly lower incidenceof complications (268 vs 479 Plt0001) particularlyphlebitis and catheter-related infections No hydrothoraxcomplications occurred in both groupsHydrothorax compli-cations have been reported to occur regardless of the size ormaterial of the PICC [23] Nevertheless Pezzati et al carriedout a retrospective study involving 280 PICCs in 258 pretermneonates and found that no pleural effusion or cardiactamponades occurred in the silastic PICC group (232280829) whereas there was one case of pleural effusion andfive of cardiac tamponades in the polyurethane PICC group(48280 171) Based on these results Pezzati et al suggestedthat silastic catheters are safer and should be preferred overpolyurethane ones [24] We found no significant differencesin the rate of total complications and catheter-related infec-tions between the two types of PICC catheters but there wasa significantly lower incidence of complications of occlusionphlebitis displacement and breakage and a higher incidenceof pleural effusion in polyurethane PICCs Among the infantswho received total parenteral nutrition via PICC threeinfants suffered from PICC-induced hydrothorax Pleuralfluid accumulation can occur due to SVC obstruction withobstruction of lymphatic drainage and erosion or perforation
BioMed Research International 5
of the catheter through the vein into the pleural space In ourexperience all the three neonates initially had polyurethanePICCs in their SVC but two of the PICCs came out dueto migration We suspect that as polyurethane PICCs arestiffer and less flexible than silastic catheters they can moreeasily damage the vascular wall when placed in the SVC dueto the curve of the aortic arch In addition similar to theprevious study we also suggest choosing silastic cathetersover polyurethane ones especially in the case of ELBWbabies If the use of a polyurethane catheter is unavoidable wewould recommend using the saphenous approach in order toavoid the aortic curve A large-scale prospective randomizedmulticenter study is required to evaluate the incidence ofpleural effusion and cardiac tamponades in these two typesof PICCs
This study has several limitations First this was anobservational study and is therefore vulnerable to bias Theline tip position was also not regularly monitored norwas thrombosis identified via ultrasound Secondly somecatheter infections may have been treated with antibioticswhile the PICC remained in place and these complicationsmay not have been captured Finally despite this beinga large cohort our findings may not be generalizable asthis was a single-center study Larger prospective studiesacross multiple centers are needed to clarify the relationshipbetween these possible risk factors and PICC complications
5 Conclusion
Our prospective cohort study identified that noncentralcatheter tip position was the only independent risk factor fornonselective removal of PICC Therefore Clinicians shouldensure that catheter tips reside in the RA IVC or SVC at orabove the level of the diaphragm in neonates
Conflicts of Interest
All authors declare that there are no conflicts of interestregarding the publication of this article
References
[1] S B Ainsworth andW McGuire ldquoPeripherally inserted centralcatheters vs peripheral cannulas for delivering parenteral nutri-tion in neonatesrdquo Journal of the American Medical Associationvol 315 no 23 pp 2612-2613 2016
[2] C N Litz J G Tropf P D Danielson andNM Chandler ldquoTheidle central venous catheter in the NICU When should it beremovedrdquo Journal of Pediatric Surgery 2017
[3] M Legemaat P J Carr R M Van Rens M Van Dijk I EPoslawsky and A Van den Hoogen ldquoPeripheral intravenouscannulation Complication rates in the neonatal population Amulticenter observational studyrdquo Journal of Vascular Access vol17 no 4 pp 360ndash365 2016
[4] A S McCay E C Elliott and M Walden ldquoVideos in clinicalmedicine PICC placement in the neonaterdquo The New EnglandJournal of Medicine vol 370 no 11 p e17 2014
[5] M-Y Hei X-C Zhang X-Y Gao et al ldquoCatheter-relatedinfection and pathogens of umbilical venous catheterization in
a neonatal intensive care unit in Chinardquo American Journal ofPerinatology vol 29 no 2 pp 107ndash114 2012
[6] F Soroush A Zargham-Boroujeni and M Namnabati ldquoTherelationship between nurses1015840 clinical competence and burnoutin neonatal intensive care unitsrdquo Iranian Journal of Nursing andMidwifery Research vol 21 no 4 p 424 2016
[7] A M Milstone N G Reich S Advani et al ldquoCatheter dwelltime and clabsis in neonates with piccs A multicenter cohortstudyrdquo Pediatrics vol 132 no 6 pp e1609ndashe1615 2013
[8] A Jain P Deshpande and P Shah ldquoPeripherally insertedcentral catheter tip position and risk of associated complicationsin neonatesrdquo Journal of Perinatology vol 33 no 4 pp 307ndash3122013
[9] V Chopra D Ratz L Kuhn T Lopus C Chenoweth andS Krein ldquoPICC-associated bloodstream infections Prevalencepatterns and predictorsrdquoAmerican Journal ofMedicine vol 127no 4 pp 319ndash328 2014
[10] J M Racadio D A Doellman N D Johnson J A Bean andB R Jacobs ldquoPediatric peripherally inserted central catheterscomplication rates related to catheter tip locationrdquo Pediatricsvol 107 no 2 p E28 2001
[11] P Kisa J Ting A Callejas H Osiovich and S A ButterworthldquoMajor thrombotic complications with lower limb PICCs insurgical neonatesrdquo Journal of Pediatric Surgery vol 50 no 5pp 786ndash789 2015
[12] V Hoang J Sills M Chandler E Busalani R Clifton-Koeppeland H D Modanlou ldquoPercutaneously inserted central catheterfor total parenteral nutrition in neonates Complications ratesrelated to upper versus lower extremity insertionrdquo Pediatricsvol 121 no 5 pp e1152ndashe1159 2008
[13] P Panagiotounakou G Antonogeorgos E Gounari SPapadakis J Labadaridis and A K Gounaris ldquoPeripherallyinserted central venous catheters Frequency of complicationsin premature newborn depends on the insertion siterdquo Journalof Perinatology vol 34 no 6 pp 461ndash463 2014
[14] X Li H Wang Y Chen and Z Yuan ldquoMultifactor analysisof malposition of peripherally inserted central catheters inpatients with cancerrdquo Clinical Journal of Oncology Nursing vol19 no 4 pp E70ndashE73 2015
[15] I Njere S Islam D Parish J Kuna and A S KeshtgarldquoOutcome of peripherally inserted central venous catheters insurgical andmedical neonatesrdquo Journal of Pediatric Surgery vol46 no 5 pp 946ndash950 2011
[16] K Colacchio Y Deng V Northrup and M J BizzarroldquoComplications associated with central and non-central venouscatheters in a neonatal intensive care unitrdquo Journal of Perinatol-ogy vol 32 no 12 pp 941ndash946 2012
[17] Y Ohki K Maruyama A Harigaya M Kohno and HArakawa ldquoComplications of peripherally inserted centralvenous catheter in Japanese neonatal intensive care unitsrdquoPediatrics International vol 55 no 2 pp 185ndash189 2013
[18] D W Cartwright ldquoCentral venous lines in neonates A study of2186 cathetersrdquoADC - Fetal and Neonatal Edition vol 89 no 6pp F504ndashF508 2004
[19] K Jumani S Advani N G Reich L Gosey andAMMilstoneldquoRisk factors for peripherally inserted central venous cathetercomplications in childrenrdquo JAMA Pediatrics vol 167 no 5 pp429ndash435 2013
[20] J Moran C Y Colbert J Song et al ldquoScreening for novelrisk factors related to peripherally inserted central catheter-associated complicationsrdquo Journal of Hospital Medicine vol 9no 8 pp 481ndash489 2014
6 BioMed Research International
[21] F Eifinger K Brisken B Roth and J Koebke ldquoTopographicalanatomyof central venous system in extremely low-birthweightneonates less than 1000 grams and the effect of central venouscatheter placementrdquoClinical Anatomy vol 24 no 6 pp 711ndash7162011
[22] C K Ong S K Venkatesh G B Lau and S CWang ldquoProspec-tive randomized comparative evaluation of proximal valvepolyurethane and distal valve silicone peripherally inserted cen-tral cathetersrdquo Journal of Vascular and Interventional Radiologyvol 21 no 8 pp 1191ndash1196 2010
[23] J A Leipala J Petaja and V Fellman ldquoPerforation compli-cations of percutaneous central venous catheters in very lowbirthweight infantsrdquo Journal of Paediatrics andChildHealth vol37 no 2 pp 168ndash171 2001
[24] M Pezzati L Filippi G Chiti et al ldquoCentral venous cathetersand cardiac tamponade in preterm infantsrdquo Intensive CareMedicine vol 30 no 12 pp 2253ndash2256 2004
Computational and Mathematical Methods in Medicine
Hindawiwwwhindawicom Volume 2018
Behavioural Neurology
OphthalmologyJournal of
Hindawiwwwhindawicom Volume 2018
Diabetes ResearchJournal of
Hindawiwwwhindawicom Volume 2018
Hindawiwwwhindawicom Volume 2018
Research and TreatmentAIDS
Hindawiwwwhindawicom Volume 2018
Gastroenterology Research and Practice
Hindawiwwwhindawicom Volume 2018
Parkinsonrsquos Disease
Evidence-Based Complementary andAlternative Medicine
Volume 2018Hindawiwwwhindawicom
Submit your manuscripts atwwwhindawicom
4 BioMed Research International
Table 4 Univariable logistic analysis for PICCs complications
OR 95CI pGestational age 0860 (07440994) 0041Birth weight lt1500 g 1291 (06902417) 0425Boy 0721 (03931324) 0292Surgery 1586 (04515577) 0472Left side 2063 (06736326) 0205Non-upper limbs insertion site 0485 (01691394) 0179Silastic 1447 (07142932) 0305PICC dwell time 0980 (09521009) 0174Non-central 2718 (13935303) 0003
Table 5 Multivariable logistic analysis for PICCs complications
OR 95CI pGestational age 0830 (06871003) 0053Birth weight lt1500 g 1030 (04362437) 0946Boy 0582 (02941154) 0121PICC dwell time 0979 (09481010) 0184Non-central tip position 2621 (12585461) 0010
tips Moreover factors such as small vessel size decreasedblood flow rate turbulent flow and endothelial injury areconsidered to contribute to these complications In our studyalthough noncentrally located PICCs represented a smallpercentage (167) of inserted PICCs They were more likelyto be removed secondary to a complication compared withPICCs with a central tip position
Previous studies have reported nonselective removal ratesranging 29-208 [17ndash20] The rates of complications in ourstudy are similar to those reported previously Despite thelower rates of complications associated with centrally locatedPICCs often it is not possible to achieve centrally locatedPICCs due to factors such as venospasm venous tortuosityand venous valves [19] There is no clear evidence in theliterature indicating the association of catheter tip positionand complication rates in pediatric PICCs Some pediatricstudies have found that PICCs placed in noncentral veinsprovided safe and reliable intravenous access [17] whereasothers have suggested that PICCs terminating in noncentralvenous positions have higher risks of complication [10 16 19]Nevertheless these studies cannot be easily compared dueto inconsistent definitions of central veins Some authorshave classified the subclavian vein as a central positionfor the catheter tip Most clinicians consider a PICC toterminate in a central vein if the tip is located in the IVCSVC or right atrial junction (RAJ) After adjusting for otherimportant predictors of PICC complications such as agecatheter dwell time PICC insertion site and indications forPICC insertion our findings are in linewith previous findingsthat a noncentral catheter tip position is associated withincreased rates of nonselective removal
Increased complication rates in noncentral PICCs espe-cially mechanical complications may be the result of a
combination of factors such as vessel size turbulence bloodflow rate and endothelial injury A cadaveric study of ELBWinfants revealed that the outer diameter of the subclavianveins was significantly smaller than the BC (mean diametersof 26 and 25 mm vs 33 and 40 mm for the right andleft respectively) [21] The outer diameter of vessels withthe catheter tip may be inversely related to the rate ofmechanical and infiltrative complications In another studythe researchers discouraged the insertion of PICC tips in sub-clavian veins in neonates because catheters located in theseveins had a higher rate of infiltration and mechanical com-plications and shorter time to complications [8] The resultsof the present study suggested that noncentral catheters werean independent risk factor for noninfectious complicationsTherefore noncentrally located PICCs should be used withcaution due to their increased risk of complication
Ong et al carried out a prospective randomized studyto compare the complications between polyurethane andsilicone PICCs [22] They randomly assigned 326 patients toa proximal valve polyurethane PICC or a distal valve siliconePICC Polyurethane PICCs were found to be more durablethan silicone PICCs with a significantly lower incidenceof complications (268 vs 479 Plt0001) particularlyphlebitis and catheter-related infections No hydrothoraxcomplications occurred in both groupsHydrothorax compli-cations have been reported to occur regardless of the size ormaterial of the PICC [23] Nevertheless Pezzati et al carriedout a retrospective study involving 280 PICCs in 258 pretermneonates and found that no pleural effusion or cardiactamponades occurred in the silastic PICC group (232280829) whereas there was one case of pleural effusion andfive of cardiac tamponades in the polyurethane PICC group(48280 171) Based on these results Pezzati et al suggestedthat silastic catheters are safer and should be preferred overpolyurethane ones [24] We found no significant differencesin the rate of total complications and catheter-related infec-tions between the two types of PICC catheters but there wasa significantly lower incidence of complications of occlusionphlebitis displacement and breakage and a higher incidenceof pleural effusion in polyurethane PICCs Among the infantswho received total parenteral nutrition via PICC threeinfants suffered from PICC-induced hydrothorax Pleuralfluid accumulation can occur due to SVC obstruction withobstruction of lymphatic drainage and erosion or perforation
BioMed Research International 5
of the catheter through the vein into the pleural space In ourexperience all the three neonates initially had polyurethanePICCs in their SVC but two of the PICCs came out dueto migration We suspect that as polyurethane PICCs arestiffer and less flexible than silastic catheters they can moreeasily damage the vascular wall when placed in the SVC dueto the curve of the aortic arch In addition similar to theprevious study we also suggest choosing silastic cathetersover polyurethane ones especially in the case of ELBWbabies If the use of a polyurethane catheter is unavoidable wewould recommend using the saphenous approach in order toavoid the aortic curve A large-scale prospective randomizedmulticenter study is required to evaluate the incidence ofpleural effusion and cardiac tamponades in these two typesof PICCs
This study has several limitations First this was anobservational study and is therefore vulnerable to bias Theline tip position was also not regularly monitored norwas thrombosis identified via ultrasound Secondly somecatheter infections may have been treated with antibioticswhile the PICC remained in place and these complicationsmay not have been captured Finally despite this beinga large cohort our findings may not be generalizable asthis was a single-center study Larger prospective studiesacross multiple centers are needed to clarify the relationshipbetween these possible risk factors and PICC complications
5 Conclusion
Our prospective cohort study identified that noncentralcatheter tip position was the only independent risk factor fornonselective removal of PICC Therefore Clinicians shouldensure that catheter tips reside in the RA IVC or SVC at orabove the level of the diaphragm in neonates
Conflicts of Interest
All authors declare that there are no conflicts of interestregarding the publication of this article
References
[1] S B Ainsworth andW McGuire ldquoPeripherally inserted centralcatheters vs peripheral cannulas for delivering parenteral nutri-tion in neonatesrdquo Journal of the American Medical Associationvol 315 no 23 pp 2612-2613 2016
[2] C N Litz J G Tropf P D Danielson andNM Chandler ldquoTheidle central venous catheter in the NICU When should it beremovedrdquo Journal of Pediatric Surgery 2017
[3] M Legemaat P J Carr R M Van Rens M Van Dijk I EPoslawsky and A Van den Hoogen ldquoPeripheral intravenouscannulation Complication rates in the neonatal population Amulticenter observational studyrdquo Journal of Vascular Access vol17 no 4 pp 360ndash365 2016
[4] A S McCay E C Elliott and M Walden ldquoVideos in clinicalmedicine PICC placement in the neonaterdquo The New EnglandJournal of Medicine vol 370 no 11 p e17 2014
[5] M-Y Hei X-C Zhang X-Y Gao et al ldquoCatheter-relatedinfection and pathogens of umbilical venous catheterization in
a neonatal intensive care unit in Chinardquo American Journal ofPerinatology vol 29 no 2 pp 107ndash114 2012
[6] F Soroush A Zargham-Boroujeni and M Namnabati ldquoTherelationship between nurses1015840 clinical competence and burnoutin neonatal intensive care unitsrdquo Iranian Journal of Nursing andMidwifery Research vol 21 no 4 p 424 2016
[7] A M Milstone N G Reich S Advani et al ldquoCatheter dwelltime and clabsis in neonates with piccs A multicenter cohortstudyrdquo Pediatrics vol 132 no 6 pp e1609ndashe1615 2013
[8] A Jain P Deshpande and P Shah ldquoPeripherally insertedcentral catheter tip position and risk of associated complicationsin neonatesrdquo Journal of Perinatology vol 33 no 4 pp 307ndash3122013
[9] V Chopra D Ratz L Kuhn T Lopus C Chenoweth andS Krein ldquoPICC-associated bloodstream infections Prevalencepatterns and predictorsrdquoAmerican Journal ofMedicine vol 127no 4 pp 319ndash328 2014
[10] J M Racadio D A Doellman N D Johnson J A Bean andB R Jacobs ldquoPediatric peripherally inserted central catheterscomplication rates related to catheter tip locationrdquo Pediatricsvol 107 no 2 p E28 2001
[11] P Kisa J Ting A Callejas H Osiovich and S A ButterworthldquoMajor thrombotic complications with lower limb PICCs insurgical neonatesrdquo Journal of Pediatric Surgery vol 50 no 5pp 786ndash789 2015
[12] V Hoang J Sills M Chandler E Busalani R Clifton-Koeppeland H D Modanlou ldquoPercutaneously inserted central catheterfor total parenteral nutrition in neonates Complications ratesrelated to upper versus lower extremity insertionrdquo Pediatricsvol 121 no 5 pp e1152ndashe1159 2008
[13] P Panagiotounakou G Antonogeorgos E Gounari SPapadakis J Labadaridis and A K Gounaris ldquoPeripherallyinserted central venous catheters Frequency of complicationsin premature newborn depends on the insertion siterdquo Journalof Perinatology vol 34 no 6 pp 461ndash463 2014
[14] X Li H Wang Y Chen and Z Yuan ldquoMultifactor analysisof malposition of peripherally inserted central catheters inpatients with cancerrdquo Clinical Journal of Oncology Nursing vol19 no 4 pp E70ndashE73 2015
[15] I Njere S Islam D Parish J Kuna and A S KeshtgarldquoOutcome of peripherally inserted central venous catheters insurgical andmedical neonatesrdquo Journal of Pediatric Surgery vol46 no 5 pp 946ndash950 2011
[16] K Colacchio Y Deng V Northrup and M J BizzarroldquoComplications associated with central and non-central venouscatheters in a neonatal intensive care unitrdquo Journal of Perinatol-ogy vol 32 no 12 pp 941ndash946 2012
[17] Y Ohki K Maruyama A Harigaya M Kohno and HArakawa ldquoComplications of peripherally inserted centralvenous catheter in Japanese neonatal intensive care unitsrdquoPediatrics International vol 55 no 2 pp 185ndash189 2013
[18] D W Cartwright ldquoCentral venous lines in neonates A study of2186 cathetersrdquoADC - Fetal and Neonatal Edition vol 89 no 6pp F504ndashF508 2004
[19] K Jumani S Advani N G Reich L Gosey andAMMilstoneldquoRisk factors for peripherally inserted central venous cathetercomplications in childrenrdquo JAMA Pediatrics vol 167 no 5 pp429ndash435 2013
[20] J Moran C Y Colbert J Song et al ldquoScreening for novelrisk factors related to peripherally inserted central catheter-associated complicationsrdquo Journal of Hospital Medicine vol 9no 8 pp 481ndash489 2014
6 BioMed Research International
[21] F Eifinger K Brisken B Roth and J Koebke ldquoTopographicalanatomyof central venous system in extremely low-birthweightneonates less than 1000 grams and the effect of central venouscatheter placementrdquoClinical Anatomy vol 24 no 6 pp 711ndash7162011
[22] C K Ong S K Venkatesh G B Lau and S CWang ldquoProspec-tive randomized comparative evaluation of proximal valvepolyurethane and distal valve silicone peripherally inserted cen-tral cathetersrdquo Journal of Vascular and Interventional Radiologyvol 21 no 8 pp 1191ndash1196 2010
[23] J A Leipala J Petaja and V Fellman ldquoPerforation compli-cations of percutaneous central venous catheters in very lowbirthweight infantsrdquo Journal of Paediatrics andChildHealth vol37 no 2 pp 168ndash171 2001
[24] M Pezzati L Filippi G Chiti et al ldquoCentral venous cathetersand cardiac tamponade in preterm infantsrdquo Intensive CareMedicine vol 30 no 12 pp 2253ndash2256 2004
Computational and Mathematical Methods in Medicine
Hindawiwwwhindawicom Volume 2018
Behavioural Neurology
OphthalmologyJournal of
Hindawiwwwhindawicom Volume 2018
Diabetes ResearchJournal of
Hindawiwwwhindawicom Volume 2018
Hindawiwwwhindawicom Volume 2018
Research and TreatmentAIDS
Hindawiwwwhindawicom Volume 2018
Gastroenterology Research and Practice
Hindawiwwwhindawicom Volume 2018
Parkinsonrsquos Disease
Evidence-Based Complementary andAlternative Medicine
Volume 2018Hindawiwwwhindawicom
Submit your manuscripts atwwwhindawicom
BioMed Research International 5
of the catheter through the vein into the pleural space In ourexperience all the three neonates initially had polyurethanePICCs in their SVC but two of the PICCs came out dueto migration We suspect that as polyurethane PICCs arestiffer and less flexible than silastic catheters they can moreeasily damage the vascular wall when placed in the SVC dueto the curve of the aortic arch In addition similar to theprevious study we also suggest choosing silastic cathetersover polyurethane ones especially in the case of ELBWbabies If the use of a polyurethane catheter is unavoidable wewould recommend using the saphenous approach in order toavoid the aortic curve A large-scale prospective randomizedmulticenter study is required to evaluate the incidence ofpleural effusion and cardiac tamponades in these two typesof PICCs
This study has several limitations First this was anobservational study and is therefore vulnerable to bias Theline tip position was also not regularly monitored norwas thrombosis identified via ultrasound Secondly somecatheter infections may have been treated with antibioticswhile the PICC remained in place and these complicationsmay not have been captured Finally despite this beinga large cohort our findings may not be generalizable asthis was a single-center study Larger prospective studiesacross multiple centers are needed to clarify the relationshipbetween these possible risk factors and PICC complications
5 Conclusion
Our prospective cohort study identified that noncentralcatheter tip position was the only independent risk factor fornonselective removal of PICC Therefore Clinicians shouldensure that catheter tips reside in the RA IVC or SVC at orabove the level of the diaphragm in neonates
Conflicts of Interest
All authors declare that there are no conflicts of interestregarding the publication of this article
References
[1] S B Ainsworth andW McGuire ldquoPeripherally inserted centralcatheters vs peripheral cannulas for delivering parenteral nutri-tion in neonatesrdquo Journal of the American Medical Associationvol 315 no 23 pp 2612-2613 2016
[2] C N Litz J G Tropf P D Danielson andNM Chandler ldquoTheidle central venous catheter in the NICU When should it beremovedrdquo Journal of Pediatric Surgery 2017
[3] M Legemaat P J Carr R M Van Rens M Van Dijk I EPoslawsky and A Van den Hoogen ldquoPeripheral intravenouscannulation Complication rates in the neonatal population Amulticenter observational studyrdquo Journal of Vascular Access vol17 no 4 pp 360ndash365 2016
[4] A S McCay E C Elliott and M Walden ldquoVideos in clinicalmedicine PICC placement in the neonaterdquo The New EnglandJournal of Medicine vol 370 no 11 p e17 2014
[5] M-Y Hei X-C Zhang X-Y Gao et al ldquoCatheter-relatedinfection and pathogens of umbilical venous catheterization in
a neonatal intensive care unit in Chinardquo American Journal ofPerinatology vol 29 no 2 pp 107ndash114 2012
[6] F Soroush A Zargham-Boroujeni and M Namnabati ldquoTherelationship between nurses1015840 clinical competence and burnoutin neonatal intensive care unitsrdquo Iranian Journal of Nursing andMidwifery Research vol 21 no 4 p 424 2016
[7] A M Milstone N G Reich S Advani et al ldquoCatheter dwelltime and clabsis in neonates with piccs A multicenter cohortstudyrdquo Pediatrics vol 132 no 6 pp e1609ndashe1615 2013
[8] A Jain P Deshpande and P Shah ldquoPeripherally insertedcentral catheter tip position and risk of associated complicationsin neonatesrdquo Journal of Perinatology vol 33 no 4 pp 307ndash3122013
[9] V Chopra D Ratz L Kuhn T Lopus C Chenoweth andS Krein ldquoPICC-associated bloodstream infections Prevalencepatterns and predictorsrdquoAmerican Journal ofMedicine vol 127no 4 pp 319ndash328 2014
[10] J M Racadio D A Doellman N D Johnson J A Bean andB R Jacobs ldquoPediatric peripherally inserted central catheterscomplication rates related to catheter tip locationrdquo Pediatricsvol 107 no 2 p E28 2001
[11] P Kisa J Ting A Callejas H Osiovich and S A ButterworthldquoMajor thrombotic complications with lower limb PICCs insurgical neonatesrdquo Journal of Pediatric Surgery vol 50 no 5pp 786ndash789 2015
[12] V Hoang J Sills M Chandler E Busalani R Clifton-Koeppeland H D Modanlou ldquoPercutaneously inserted central catheterfor total parenteral nutrition in neonates Complications ratesrelated to upper versus lower extremity insertionrdquo Pediatricsvol 121 no 5 pp e1152ndashe1159 2008
[13] P Panagiotounakou G Antonogeorgos E Gounari SPapadakis J Labadaridis and A K Gounaris ldquoPeripherallyinserted central venous catheters Frequency of complicationsin premature newborn depends on the insertion siterdquo Journalof Perinatology vol 34 no 6 pp 461ndash463 2014
[14] X Li H Wang Y Chen and Z Yuan ldquoMultifactor analysisof malposition of peripherally inserted central catheters inpatients with cancerrdquo Clinical Journal of Oncology Nursing vol19 no 4 pp E70ndashE73 2015
[15] I Njere S Islam D Parish J Kuna and A S KeshtgarldquoOutcome of peripherally inserted central venous catheters insurgical andmedical neonatesrdquo Journal of Pediatric Surgery vol46 no 5 pp 946ndash950 2011
[16] K Colacchio Y Deng V Northrup and M J BizzarroldquoComplications associated with central and non-central venouscatheters in a neonatal intensive care unitrdquo Journal of Perinatol-ogy vol 32 no 12 pp 941ndash946 2012
[17] Y Ohki K Maruyama A Harigaya M Kohno and HArakawa ldquoComplications of peripherally inserted centralvenous catheter in Japanese neonatal intensive care unitsrdquoPediatrics International vol 55 no 2 pp 185ndash189 2013
[18] D W Cartwright ldquoCentral venous lines in neonates A study of2186 cathetersrdquoADC - Fetal and Neonatal Edition vol 89 no 6pp F504ndashF508 2004
[19] K Jumani S Advani N G Reich L Gosey andAMMilstoneldquoRisk factors for peripherally inserted central venous cathetercomplications in childrenrdquo JAMA Pediatrics vol 167 no 5 pp429ndash435 2013
[20] J Moran C Y Colbert J Song et al ldquoScreening for novelrisk factors related to peripherally inserted central catheter-associated complicationsrdquo Journal of Hospital Medicine vol 9no 8 pp 481ndash489 2014
6 BioMed Research International
[21] F Eifinger K Brisken B Roth and J Koebke ldquoTopographicalanatomyof central venous system in extremely low-birthweightneonates less than 1000 grams and the effect of central venouscatheter placementrdquoClinical Anatomy vol 24 no 6 pp 711ndash7162011
[22] C K Ong S K Venkatesh G B Lau and S CWang ldquoProspec-tive randomized comparative evaluation of proximal valvepolyurethane and distal valve silicone peripherally inserted cen-tral cathetersrdquo Journal of Vascular and Interventional Radiologyvol 21 no 8 pp 1191ndash1196 2010
[23] J A Leipala J Petaja and V Fellman ldquoPerforation compli-cations of percutaneous central venous catheters in very lowbirthweight infantsrdquo Journal of Paediatrics andChildHealth vol37 no 2 pp 168ndash171 2001
[24] M Pezzati L Filippi G Chiti et al ldquoCentral venous cathetersand cardiac tamponade in preterm infantsrdquo Intensive CareMedicine vol 30 no 12 pp 2253ndash2256 2004
Computational and Mathematical Methods in Medicine
Hindawiwwwhindawicom Volume 2018
Behavioural Neurology
OphthalmologyJournal of
Hindawiwwwhindawicom Volume 2018
Diabetes ResearchJournal of
Hindawiwwwhindawicom Volume 2018
Hindawiwwwhindawicom Volume 2018
Research and TreatmentAIDS
Hindawiwwwhindawicom Volume 2018
Gastroenterology Research and Practice
Hindawiwwwhindawicom Volume 2018
Parkinsonrsquos Disease
Evidence-Based Complementary andAlternative Medicine
Volume 2018Hindawiwwwhindawicom
Submit your manuscripts atwwwhindawicom
6 BioMed Research International
[21] F Eifinger K Brisken B Roth and J Koebke ldquoTopographicalanatomyof central venous system in extremely low-birthweightneonates less than 1000 grams and the effect of central venouscatheter placementrdquoClinical Anatomy vol 24 no 6 pp 711ndash7162011
[22] C K Ong S K Venkatesh G B Lau and S CWang ldquoProspec-tive randomized comparative evaluation of proximal valvepolyurethane and distal valve silicone peripherally inserted cen-tral cathetersrdquo Journal of Vascular and Interventional Radiologyvol 21 no 8 pp 1191ndash1196 2010
[23] J A Leipala J Petaja and V Fellman ldquoPerforation compli-cations of percutaneous central venous catheters in very lowbirthweight infantsrdquo Journal of Paediatrics andChildHealth vol37 no 2 pp 168ndash171 2001
[24] M Pezzati L Filippi G Chiti et al ldquoCentral venous cathetersand cardiac tamponade in preterm infantsrdquo Intensive CareMedicine vol 30 no 12 pp 2253ndash2256 2004
