https://orcid.org/0000-0001-5546-023X
Figures
Abstract
Background
The improper handling of a peripherally inserted central catheter (PICC) in newborns (NBs) may result in mechanical and infectious complications.
Aim
The aim of this systematic review (SR) is to estimate the prevalence of complications associated with the use of PICC in NBs.
Methods
We will utilize PubMed, Embase, CENTRAL, Web of Science, Scopus, Cochrane Library, CINAHL, and Google Scholar for the databases search. There will be no restrictions on the search for languages, and observational studies will be selected wherein the prevalence rate of complications associated with the use of PICC in NBs has been presented or can be calculated. The systematic review will follow the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Two reviewers will independently select studies and assess their eligibility using predefined criteria. Using standardized forms, two other reviewers will independently extract data from each included study, and the random-effects pooled prevalence will be calculated in the meta-analysis with the respective 95% confidence intervals. The methodological quality of the studies will be assessed using the modified Newcastle-Ottawa Scale. Review Manager V.5.3.5 will be used for the qualitative and quantitative synthesis. A protocol was developed and published on PROSPERO (Registration number CRD42020211983).
Citation: Sarmento Diniz ER, de Medeiros KS, Rosendo da Silva RA, Cobucci RN, Roncalli AG (2021) Prevalence of complications associated with the use of a peripherally inserted central catheter in newborns: A systematic review protocol. PLoS ONE 16(7): e0255090. https://doi.org/10.1371/journal.pone.0255090
Editor: Raffaele Serra, University Magna Graecia of Catanzaro, ITALY
Received: May 4, 2021; Accepted: July 6, 2021; Published: July 23, 2021
Copyright: © 2021 Sarmento Diniz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: Coordination for the Improvement of Higher Education Personnel (Coor-denação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES), Finance Code 001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
The insertion of peripherally inserted central catheters (PICC) is common in neonatal intensive care units (NICU) in term newborns (NBs) and premature infants receiving venous therapies with vesicant and irritating drugs and parenteral nutrition. Moreover, depending on the caliber, it is also used for blood tests, transfusion of blood products, and hemodynamic monitoring [1, 2]. These reduce the risk of complications and dispense with the need for surgical intervention, which is advantageous due to the reduced hospitalization time, reduced hospital costs, and decreased incidence of neonatal mortality, as PICC reduce the incidence of complications when compared to other central catheters [3].
Premature NBs generally have low birth weight, and many are dependent on hyperosmotic or irritating drugs, which must be administered through a long-term venous access [2]. Previous studies have identified risk factors for complications associated with the use of PICC in NBs, including gestational age (GA), catheter insertion location, catheter tip location, and catheter dwell time, especially when it is installed for greater than 35 days, a factor also associated with an increased catheter-related bloodstream infection [1, 4]. Other mechanical complications appear with a lower incidence such as rupture of the catheter, migration of the catheter tip, obstruction, and leakage of drugs [5, 6]. These are responsible for several non-elective removals, and many of these can be avoided as they are related to the improper handling of the device [3, 7].
The use of PICC in NICU has become essential in neonatal clinical practice, and monitoring of the risk factors associated with complications is part of the neonatal care quality management in developed and developing countries, in which teams responsible for the quality management adopt evidence-based strategies to prevent these complications [8, 9]. Such complications can cause an increase in the costs of health services due to the increase in the length of stay in the NICU, as well as injuries to NBs, such as tissue, cardiological, and infectious injuries. Previous studies on complications related to the use of PICC in NBs have demonstrated the prevalence of tissue complications (edema, phlebitis, enlargement, and necrosis) and systemic complications (arrhythmias, cardiac tamponade, and sepsis) [3, 10–12].
Information on the complications associated with the use of PICC in NBs is scarce, and few studies that were conducted were observations done for short periods and focused on the risk factors associated with infection, but not on the prevalence of complications [8]. Thus, it is essential to develop studies to assess the prevalence of complications related to the use of PICC in NBs. The aim of this systematic review is to estimate the prevalence of complications associated with the use of PICC in NBs.
Methods
This protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines extension for reporting systematic review protocols (PRISMA-P) [13]. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (number: CRD42020211983). The systematic review will follow the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [14, 15].
Ethics
Ethical approval is not required because this review will retrieve publicly available scientific literature. Traditional dissemination strategies will be used, including open-access peer-reviewed publications, scientific presentations, and reports.
Inclusion criteria
This systematic review will include observational studies (case-control, cross-sectional, and cohort) that describe complications associated with the use of PICC in NBs. There will be no restrictions on the search for languages and the publication period.
Exclusion criteria
Published articles, but not peer-reviewed articles, will not be included in the review. Randomized clinical trials, review articles, reports, and case series will be excluded. Studies that assessed the prevalence of complications in children (older than 28 days of life) will also be excluded.
The PECOT strategy
- Population/participants: NBs
- Exposure: PICC
- Comparator/control: NBs who do not use the PICC
- Outcome: Complications associated with the use of PICC (mechanical, infectious, and systemic)
- Types of studies: observational studies (sectional, cohort, and case-control)
Types of participants
Study participants will be NBs using PICC or not, neonates (children under 28 days of age), extremely premature (<28 weeks) NBs, very premature (28 to 31 weeks and 6 days) NBs, moderate or late preterm (32 to 36 weeks and 6 days) NBs, NBs with low birth weight, and healthy term NBs [16].
Types of exposures
The included studies will be those describing complications in neonates using PICC, a peripherally inserted central catheter that is inserted through a peripheral vein and its tip is destined for the vena cava, used for medium-and long-term intravenous infusion or therapy with irritating and vesicant drugs [17, 18].
- Control: NBs who do not use PICC.
Outcomes
- Primary outcome: Neonatal death
- Secondary outcomes:
- Pulmonary complications: pleural effusion, pneumothorax, and hydrothorax
- Cardiovascular complications: arrhythmias, myocardial perforation, and cardiac tamponade
- Tissue complications: hematomas, phlebitis, pain, local hardening, infiltration, leakage, and necrosis
- Hematological complications: bleeding, embolism, and thrombosis
- Infectious complications
Search strategy
The studies will be obtained through PubMed, Embase, CINAHL, LILACS, CENTRAL, Web of Science, Scopus, Cochrane Library, and Google Scholar databases. There will be no restrictions on the search for languages and year of publication. Articles will also be searched from the references of the selected studies, and the search strategy used in PubMed is shown in Table 1.
Data collection and analysis
Study selection.
After searching the databases, all identified articles will be exported to Rayyan software and duplicates will be removed. First, the titles and abstracts will be read independently by at least two reviewers (ERSD and KSM) based on the inclusion criteria. The full texts of these potentially eligible studies will be retrieved and taken independently for eligibility by two members of the review team (ERSD and RNC). Only studies identified by both pairs of reviewers based on the inclusion criteria will ultimately be included in the systematic review, and a third reviewer (RAS) will make a final decision for inclusion in case of discrepancy.
We will maintain a record of the reasons for excluding clinical trials at all stages of the review. The results of the selection or exclusion of the studies will be reported using the PRISMA flowchart, as shown in Fig 1.
Data extraction.
Using standardized forms, two reviewers (ERSD and KSM) independently will extract the following data from each included study: first author, year, place of study, population and sample, type of study, objective, design, variables analyzed (GA of the NB, NB weight, NB diagnosis, catheter insertion location, use of parenteral nutrition, use of vasoactive drugs and antibiotics, time of use of PICC), and complications associated with the use of PICC. The extracted data cover the issue of the review and will be verified again by three authors (RNC, RAS, and AGR).
Addressing missing data.
In case of a lack of data, the authors of this article will contact the respective authors or co-authors of the article in question by telephone or e-mail. If information will not be received, the data will be excluded from our analysis and will be covered in the discussion section.
Quality assessment of the included studies.
The methodological quality of the selected studies will be assessed using the modified Newcastle-Ottawa Scale [19]. The following items will be analyzed: exposure, comparability, sample representativeness, sample size, response rate, outcome assessment, and statistics. The classification of the methodological quality of the studies will be carried out considering the total number of points received: ≥ 4 for good quality and <4 for low quality. The divergences found will be discussed and resolved by 3 authors of the review (ERSD, RNC, and LNS) [20].
Assessment of heterogeneity
Measures of treatment effect.
The results of the systematic review will be written in a structured manner with respect to the characteristics of the target population, type of primary outcomes (neonatal death), and secondary outcomes (systemic and tissue complications, rupture of the catheter and others).
The general prevalence of complications in NBs with PICC will be calculated using the random effects model, considering the heterogeneity between the studies included in the review. Cochran’s Q test will be used to assess heterogeneity and the I² statistic for quantification. The result of I² ≤ 50% will be considered as low heterogeneity and, in this case, the fixed effects model will be used. For I²> 50%, high heterogeneity, the random effects model will be used to calculate the prevalence ratio and 95% confidence interval (95% CI). When possible, we will use Egger’s funnel plot to assess possible publication bias.
Data synthesis.
A quantitative synthesis (meta-analysis) will be performed in the RevMan 5.3.5 software using the inverse variance method with the random effects model if there is more than 50% heterogeneity between the studies. In cases where the data will be insufficient to calculate an effect estimate, a narrative synthesis will be created, describing the direction and size of the effects, along with any reported accuracy measures.
Subgroup and sensitivity analysis.
Sensitivity analysis will be conducted to verify possible sources of heterogeneity, removing one study at a time, and verifying if there is a considerable change in the prevalence estimate and 95% CI. Sensitivity analysis will be performed excluding studies with a high risk of bias. When the effect estimates of the primary and sensitivity analyses are significantly different, an adjusted sensitivity analysis will be performed.
We plan to perform the following subgroup analyses, wherever possible: type of complication found (local versus systemic), GA, weight, diagnosis, days of life, and indications for the use of PICC. If we identify significant differences between the subgroups (test for interaction <0.05), we will report the results for individual subgroups separately. We will also perform a formal test for subgroup interactions using the RevMan version 5.3.5.
Grading quality of evidence
Assessment of certainty of evidence.
The analysis of the evidence for all outcomes will be assessed using the Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) methodology [21] by classifying the evidence as high, moderate, low, or very low.
Discussion
Knowledge about the actual prevalence of complications resulting from the use of PICC is essential for clinical practice in NICU and may allow the adoption of strategies that reduce those that are more serious, which can lead to the death of NBs. Previous studies have revealed a strong association between the time of NBs exposure to PICC during administration of parenteral nutrition and the use of antimicrobials with the development of complications, especially bloodstream infection [22–24]. However, systematic reviews of the prevalence of these complications are scarce.
A previous meta-analysis revealed that PICC inserted in the lower limbs did not show worse results compared to the upper limb group in the NICU, apart from thrombosis [25]. A finding divergent from this was demonstrated by Pet et al., who reported the occurrence of complications more frequently with PICC inserted in the upper extremities than in the lower extremities [26]. In another study, it was observed that the insertion of the PICC in the first 48 hours of life did not increase the prevalence of complications [12].
A recent study conducted in Greece revealed that the complication rates were similar when comparing the types of catheters used in NBs with low birth weight, and the authors recommend that central venous catheters should be removed early in NICU [27]. Studies have shown that low birth weight is a risk factor for complications associated with PICC in the NICU, and Wen et al. demonstrated that infectious and non-infectious complications of PICC are associated with low weight gain in premature babies [27, 28]. However, there is no reliable data on the actual prevalence of complications of PICC use in premature or low birth weight infants.
Biofilm is a fundamental component in the pathogenesis of infectious complications of PICC. Biofilm can be the cause of PICC extraction and can lead to serious haematogenic infectious complications that can increase the morbidity and mortality of affected babies. In order to help physicians and nurses to better target their preventive and therapeutic measures, will be important to understand which organism has the greatest impact on the development of PICC related bloodstream infections and to study the prevalence of the conditions worldwide, since effective prevention represent a sensitive target to reduce the prevalence of infectious complications during the use of PICC [29].
The potential limitations of the systematic review will focus on several aspects of the study design, searches, and quality appraisal of included studies. Limitations are related to include cross-sectional and case-control studies to hinder the reliable assessment of the causal relationship between PICC and complications in NBs. Furthermore, a small sample size and a limited number of studies can influence the validity and reliability of the findings.
Therefore, this systematic review will be carried out using a specific approach with a meta-analysis of the included studies results if possible. It is justified because knowing the prevalence of complications associated with the use of PICC in NBs in the NICU can positively impact the practice of care for the NB during infusion therapy and allow the creation of strategies to reduce serious complications such as sepsis and death. We expect that it will show the prevalence of complications caused by the inadequate management of PICC in NBs, which is information considered important for clinical practice improvement.
Supporting information
S1 Checklist. Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P checklist).
https://doi.org/10.1371/journal.pone.0255090.s001
(DOCX)
References
- 1. Rosado V, Camargos PA, Anchieta LM, Bouzada MC, Oliveira GM, Clemente WT, et al. Risk factors for central venous catheter-related infections in a neonatal population: systematic review. J Pediatr. 2018; 94:3–14. https://doi.org/10.1016/j.jped.2017.03.012 pmid:28866323
- 2. Li Renfeng, Xia C, Tian S, Lei X. Application of peripherally inserted central catheters in critically ill newborns experience from a neonatal intensive care unit. Medicine [Internet]. 2019; 98:32. https://doi.org/10.1097/MD.0000000000015837 pmid:31393341
- 3. Xiaohe Y, Shaojie Y, Mingjie W, Chuanding C, Zhengchang L, Ying D, et al. Risk Factors Related to Peripherally Inserted Central Venous Catheter Nonselective Removal in Neonates. BioMed Research International 2018; Screens:1–6. https://doi.org/10.1155/2018/3769376 pmid:30003096
- 4. Milstone AM, Reich NG, Advani S, et al. Catheter dwell time and CLABSIs in neonates with PICCs: a multicenter cohort study. Pediatrics 2013; 132: e1609–15. https://doi.org/10.1542/peds.2013-1645 pmid:24218474
- 5. Vashi PG, Virginkar N, Popiel B, Edwin P, Gupta D. Incidence of and factors associated with catheter-related bloodstream infection in patients with advanced solid tumors on home parenteral nutrition managed using a standardized catheter care protocol. BMC Infectious Diseases. 2017; 17: 372. https://doi.org/10.1186/s12879-017-2469-7 pmid:28558699
- 6. Sukyung K, Soo mi S, Seoul HL, Kim JH, Kim H, Kim JY, et al. Outcomes of bedside peripherally inserted central catheter placement: a retrospective study at a single institution. Acute and Critical Care. 2020; 35(1): 31–37. https://doi.org/10.4266/acc.2019.00731 pmid:32131579
- 7. Santana FG, Dias PLM. Central Catheter of Peripheral Insertion in Pediatric Oncology: a Retrospective Study. Brazilian Journal of Cancerology. 2018; 64 (3): 341–347. https://doi.org/10.32635/2176-9745.RBC.2018v64n3.34
- 8. Hermansen MC, Hermansen MG. Intravascular catheter complications in the neonatal intensive care unit. Clin Perinatol. 2005; 32: 141–56. https://doi.org/10.1016/j.clp.2004.11.005 pmid:15777826
- 9. Franceschi AT, Cunha ML. Adverse events related to the use of central venous catheters in hospitalized newborns. Rev Latino-Am Enfermagem. 2010; 18. Screens 57–63. https://doi.org/10.1590/s0104-11692010000200009 pmid:20549118
- 10. Panagiotounakou P, Antonogeorgos G, Gounari E, Papadakis S, Labadaridis J, Gounaris AK. Peripherally inserted central venous catheters: frequency of complications in premature newborn depends on the insertion site. Journal of Perinatology. 2014; 34: 461–463. https://doi.org/10.1038/jp.2014.36 pmid:24625519
- 11. Singh A, Bajpai M, Panda SS, Jana M. Complications of peripherally inserted central venous catheters in neonates: Lesson leamed over 2 years in tertiary care center in India.Afr J Paediatr Surg. 2014 Jul-Sep; 11 (3): 242–7. https://doi.org/10.4103/0189-6725.137334 pmid:25047317
- 12. Li R, Cao X, Shi T, Xiong L. Application of peripherally inserted central catheters in critically ill newborns experience from a neonatal intensive care unit. Medicine (Baltimore). 2019 Aug; 98 (32): e15837. https://doi.org/10.1097/MD.0000000000015837 pmid:31393341
- 13. Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al., PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;349: g7647. https://doi.org/10.1136/bmj.i4086 pmid:25555855
- 14. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyzes of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009; 339: b2700. https://doi.org/10.1136/bmj.b2700 pmid:19622552
- 15. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyzes: the PRISMA statement. PLoS Med 2009; 6: e1000097. https://doi.org/10.1371/journal.pmed.1000097 pmid:19621072
- 16. Quinn JA, Munoz FM, Gonik B, et al. Preterm birth: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2016; 34 (49): 6047–6056. https://doi.org/10.1016/j.vaccine.2016.03.045 pmid:27743648
- 17. Westergaard B, Classen V, Walther-Larsen S. Peripherally inserted central catheters in infants and children—indications, techniques, complications and clinical recommendations. Acta Anaesthesiol Scand 2013; 57: 278–87. https://doi.org/10.1111/aas.12024 pmid:23252685
- 18. Prince A, Groh-Wargo S. Nutrition management for the promotion of growth in very low birth weight premature infants. Nutr Clin Pract 2013; 28: 659–68. https://doi.org/10.1177/0884533613506752 pmid:24163320
- 19.
Wells GA, Shea B, O’Connell D, J Peterson, V Welch, M Losos, P Tugwell. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-analyses. [Internet] Ottawa: Ottawa Hospital Research Institute. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
- 20. Stang A, Andreas S. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyzes. Eur J Epidemiol 2010; 25: 603–5. https://doi.org/10.1007/s10654-010-9491z pmid:20652370
- 21. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011 Apr;64(4):383–94. https://doi.org/10.1016/j.jclinepi.2010.04.026 pmid:21195583
- 22. Greenberg RG, Cochran KM, Smith PB, Edson BS, Schulman J, Lee HC, et al. Effect of catheter residence time on the risk of catheter-associated bloodstream infection in infants. Pediatrics 2015; 136 (6): 1080–6. https://doi.org/10.1542/peds.2015-0573 pmid:26574587
- 23. Gordon A, Greenhalgh M, McGuire W. Early planned removal versus expectant management of peripherally inserted central catheters to prevent infection in newborn infants. Cochrane Database Syst Rev. 2018 Jun 25; 6 (6): CD012141. https://doi.org/10.1002/14651858 pmid:29940073
- 24. Hoang V, Sills J, Chandler M, Busalani E, Clifton-Koeppel R, Modanlou H D. Percutaneously Inserted Central Catheter for Total Parenteral Nutrition in Neonates: Complications Rates Related to Upper Versus Lower Extremity Insertion. Pediatrics. 2008;121(5):e1152–e1159; https://doi.org/10.1542/peds.2007-1962 pmid:18390957
- 25. Chen H, Zhang X, Wang H, Hu X. Complications of upper extremity versus lower extremity placed peripherally inserted central catheters in neonatal intensive care units: A meta-analysis. Intensive Crit Care Nurs. 2020 Feb; 56: 102753. https://doi.org/10.1016/j.iccn.2019.08.003 pmid:31445794
- 26. Pet GC, Eickhoff JC, McNevin KE, Do J, McAdams RM. Risk factors for peripherally inserted central catheter complications in neonates. J Perinatol. 2020; 40: 581–588. https://doi.org/10.1038/s41372-019-0575-7 pmid:31911643
- 27. Wen J, Yu Q, Chen H, Chen N, Huang S, Cai W. Peripherally inserted central venous catheter-associated complications exert negative effects on body weight gain in neonatal intensive care units. Asia Pac J Clin Nutr. 2017; 26 (1): 1–5. https://doi.org/10.6133/apjcn.112015.07 pmid:28049254
- 28. Foo R, Fujii A, Harris JA. et al. Complications in Tunneled CVL Versus PICC Lines in Very Low Birth Weight Infants. J Perinatol. 2001; 21: 525–530. https://doi.org/10.1038/sj.jp.7210562 pmid:11774013
- 29. Ielapi N, Nicoletti E, Lorè C, Guasticchi G, Avenoso T, Barbetta A, et al. The Role of Biofilm in Central Venous Catheter Related Bloodstream Infections: Evidence-based Nursing and Review of the Literature. Rev Recent Clin Trials. 2020;15(1):22–27. https://doi.org/10.2174/1574887114666191018144739 pmid:31656155.