Extravasation injury management for neonates and children: A systematic review and aggregated case series

Abstract Background Pediatric extravasation injuries are significant healthcare‐associated injuries, with sometimes significant sequelae. Evidence‐based guidance on management is necessary to prevent permanent injury. Purpose A systematic review of the literature, including aggregated case series, investigating extravasation injury management of hospitalized pediatric patients. Data Sources PubMed, Cummulative Index to Nursing and Allied Health Literature (CINAHL), and Excerpta Medica database (EMBASE) were searched on December 13, 2021. Study Selection Primary research investigating extravasation injury management of hospitalized pediatric patients (to 18 years), published from 2010 onwards and in English, independently screened by two authors, with arbitration from a third author. Data Extraction Data regarding the study, patient (age, primary diagnosis), extravasation (site, presentation, outcome), and treatment (first aid, wound management) were extracted by two authors, with arbitration from a third author. Data Synthesis From an initial 1769 articles, 27 studies were included with extractable case data reported in 18 studies, resulting in 33 cases. No clinical trials were identified, instead, studies were primarily case studies (52%) of neonates (67%), with varied extravasation symptoms. Studies had good selection and ascertainment, but few met the causality and reporting requirements for quality assessments. Signs and symptoms varied, with scarring (45%) and necrosis (30%) commonly described. Diverse treatments were categorized into first aid, medical, surgical, and dressings. Conclusions Despite infiltration and extravasation injuries being common within pediatric healthcare, management interventions are under‐researched, with low‐quality studies and no consensus on treatments or outcomes.


INTRODUCTION
Access to the peripheral venous system for the administration of fluids and medications is a fundamental procedure within healthcare, particularly among children. 1,2 However, the use of peripheral intravenous catheters (PIVCs) is not without risk of harm. Extravasation injuries are caused by the inadvertent administration of vesicant and irritant solutions into the tissues surrounding the PIVC vessel. 3 Young children (including neonates) and those with conditions affecting communication are especially vulnerable to significant extravasation injuries due to their inability to report pain, their skin and vein fragility, and carer and staff difficulties inspecting insertion sites. 4,5 Up to 11% of pediatric patients and 70% of neonates receiving intravenous therapy will experience extravasation of an intravenous infusion. 4,[6][7][8][9] The significance of such an injury varies and is highly dependent on the location, the medication or fluid involved, concentration and volume of extravasate, dilutant used for reconstitution, reaction site, condition of surrounding skin, and time of detection and treatment. 1,3 The trauma caused by such injuries can progress to scarring and/or surgical excision of the affected area, skin grafting, and functional loss. 3 Approaches to managing extravasation primarily concentrate on pharmacological and nonpharmacological interventions to aid in preventing tissue damage, reversal agents specific to the type of extravasation, and surgical intervention if necessary. 10 The relative effectiveness of these strategies, across the variety of extravasation injuries that present in pediatrics is unclear. The aim of this study is to describe and evaluate current extravasation injury management and treatment options in use for children with extravasation, with the aim of reducing scarring and necrosis of tissue.

METHODS Design
A systematic review including synthesis via aggregated case series has been undertaken to answer the following research question and outcomes: 1. What extravasation injury management strategies are in use for hospitalized children?
2. How effective are these approaches to reduce tissue necrosis and scarring of the extravasation injury area, symptoms (pain, stinging, burning, edema around the injection site), tissue dysfunction, physical disability, compartment syndrome, and to improve quality of life?
Case reports and case series have been part of the importance of healthcare research to alert and educate fellow clinicians when robust evidence is not available. 11 Most case reports and series have been treated as a single entity without being aggregated, 11 despite their detailed description of the sequence and management of patient care. Aggregated case series methods proposed by Murad 12 suggest using evidence derived from case reports and case series to inform decision-making when no higher level evidence is available.
The tool also evaluates the methodological quality in the domains of selection, ascertainment, causality, and reporting to aid the clinicians with the quality assessment of the included study. Additionally, aggregated case series also make subgroup comparisons (e.g., age, diagnosis, gender) to allow for subgroup-specific differences to be identified, such as in signs and symptoms and case management, for example.
The review was prospectively registered with PROSPERO CRD42022307906 and has been reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. 13

Search strategy and information sources
With the aid of the health librarian, search terms were developed utilizing medical subject headings (MeSH) of "Extravasation of Diagnostic and Therapeutic Materials," "Child, Hospitalized," and "necrosis" and other correlating search terms associated with the patient/population, intervention/indicator, compare/control, and outcome (PICO) formatted research question. The search was performed on December 13, 2021 and accessed the following databases: PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Excerpta Medica database (EMBASE).
Supporting Information: Table 1 depicts the search strategy used for PubMed in this systematic review.

Eligibility criteria
Exclusion and inclusion criteria are outlined in Table 1

Study selection
Duplications were removed and titles and abstracts were screened against the inclusion and exclusion criteria independently by two authors (M. D. with J. C. or A. J. U.) using Covidence ® . 14 Full-text review was performed independently by the same process. Where eligibility was unclear arbitration was sought from the senior author. Full text of all articles included in the full-text review was sought through an institutional loan; however, a small number of articles that were unable to be obtained were excluded, and the first authors of the articles were not contacted.

Data extraction and quality appraisal
Data were extracted and reviewed for quality from eligible articles using Covidence. Reviews were independent by the first author (M.

Synthesis of case data
Quantitative case synthesis of individual case data was undertaken and reported by categorizing into age subgroups: neonates (<1 month old), children (1 month old to 10 years old), and adolescents (greater than 10 years old). 12 Results are descriptively reported.

Study characteristics
Individual characteristics of included studies (n = 27) are depicted in Table 2. Included studies were published between 2010 and 2021, predominantly within the United States (n = 8), and primarily included case series.

Critical appraisal and quality assessment
Included publications were predominantly case reports and series (see Supporting Information: Table 1). The article's quality

Treatment types
The treatment types were extracted and reported at the study level.
There were no differences between treatment types among age groups from aggregated case series.

First aid
First aid interventions were primarily used in conjunction with medical, surgical, and dressing interventions. First aid interventions, as shown in Figure 2a, were identified in 26 studies.  Stopping the IV and removal was the most common intervention, 16

Dressings
The use of dressings as an intervention, as shown in Figure 2d, was evident within 21 studies. 16 In aggregated case series, edema/swelling was the most reported sign and symptom in neonates and children pretreatment (N = 23).
There were more reports on progressing signs and symptoms after the treatment was initiated across the age groups, for example, scarring, necrosis, and calcinosis cutis. The long-term side effects were reported as retraction/restriction of movements for neonates and adolescents, and keloid scars for children. The improvement of treatments was often not reported in detail; however, tissue dysfunction and physical defects were the second most reported in neonates and children. Lastly, one study identified slough formation, 37 agitation/movement restriction, 22

(9)
Days taken for the wound to heal b However, we have taken steps to assess the potential risk of bias by implementing the quality assessment.

CONCLUSION
Ongoing research is necessary to identify and assess the effectiveness of extravasation injury management interventions in pediatrics.
Extravasations are one of the most common iatrogenic injuries inflicted on children. They can lead to lifelong sequelae such as scarring, in addition to the pain and suffering caused at the time of injury. Scant evidence is available to support the strategies aimed at treating, preventing, or defining these injuries. Similarly, without a consensus on extravasation injury staging, clinicians may have difficulty recognizing healing and therefore managing injuries appropriately.

ACKNOWLEDGMENTS
The authors would like to acknowledge and thank the health librarian for helping with the search strategy.