Intravenous (i.v.) access for the provision of medication and nutrition is a common, and in many cases essential, procedure used for children and infants in hospitals. Although adverse outcomes resulting from i.v. access are rare, the procedure is not without risk. Extravasation injuries are caused by unintended leakages from i.v. lines in which a fluid deviates from its planned pathway (the vein) into surrounding tissue. Extravasation of fluid can cause pain, inflammation, tendon or nerve damage and predispose to local and invasive infection. Initial treatments aim to reduce pain and prevent or minimise local tissue necrosis and associated functional and cosmetic impairment. Longer term treatment of severe extravasation episodes may require skin grafts and prolonged hospitalisation. The severity of injury and likelihood of long-term damage depends on a number of factors, including the type and amount of fluid extravasated, the injury site, how quickly treatment is administered and the treatment itself.1
The terms ‘extravasation’ and ‘infiltration’ are often used interchangeably in the literature but are sometimes defined separately, based on the type of fluid being administered.2 A vesicant is any medication or fluid with the potential for causing blisters, severe tissue injury, or necrosis primarily due to biochemical reactions. Vesicants can vary in type but include many cytotoxic agents (such as chemotherapies). Non-vesicants include fluids such as parenteral nutrition and antibiotics that can cause damage primarily due to the mechanical forces exerted. The distinction between ‘extravasation’ (i.e. leakage of a vesicant) and ‘infiltration’ (i.e. leakage of a non-vesicant) can sometimes cause undue confusion as these two types of event are often indistinguishable externally.3
Prevalence of extravasation injuries and risk factors
There is some uncertainty about the incidence of extravasation injuries in children in the NHS because of the absence of a centralised register, a paucity of data available from prospective studies and heterogeneity in definitions used to describe injury occurrence.1 Estimates of between 0.01% and 7% have been reported, although there is some evidence to suggest that this has reduced considerably since 2002.1 Age is an important risk factor and injuries that result in tissue necrosis seem to be more prevalent in neonates and younger infants. This is likely to be owing to their immature skin, fragile veins, lack of subcutaneous tissue, likelihood of needing longer periods of i.v. treatment and their limited ability to report pain.4,5 A UK-based survey of regional neonatal intensive care units5 (NICUs), published in 2004, estimated the incidence of extravasation injuries resulting in skin necrosis to be 38 per 1000 babies. Most (70%) of these occurred in preterm infants born before 27 weeks’ gestation.5 More recently, a Greek study4 of 1409 neonates reported a severe injury rate of 2.4%, and a Canadian children’s hospital-based study6 reported an overall rate of 0.04% per patient-day, in a population with a median age of 10 months. Nearly all of the injuries were at peripheral i.v. sites.6
The Great Ormond Street Hospital guidelines for the recognition, management and prevention of infiltration and extravasation injuries2 categorise risk factors as being device related, drug related, patient related and clinician related. Device-related factors refer to how the drug was administered and include the infusion site (distal limb vs. centrally placed), the type of cannula used and how the cannula was secured. Drug-related factors refer to what was administered and include the vesicant potential of the solution, the volume of fluid that is extravasated and the concentration of the drug. Patient-related factors refer to characteristics such as age and communication impairment. Finally, clinician-related factors refer to those administering the i.v. treatment and include: lack of knowledge of extravasation events, lack of i.v cannula or catheter placement skills and interruptions or distractions during i.v. treatment.
Managing these risk factors to prevent extravasation occurring is preferable to treating an injury. Immediate removal of the catheter and prompt treatment is thought to be important in such cases. This is often hampered by the unreliability of alarms on i.v. pumps in detecting elevated perfusion pressures that may indicate extravasations. These alarms are not intended to detect extravasations but are often the only warning sign the clinicians have to indicate flow faults during infusions.7 These devices have been shown to detect extravasation in only 19% of cases because of the variability in resistance to flow due to the rate and site of infusion.8
Litigation in extravasation injuries
About 65% of clinical negligence claims in paediatric surgery in the UK result in payment to the claimant.9 Of these, between 2% and 4% are due to extravasation events.10,11 However, a severe extravasation injury does not constitute negligence in itself. Any claims would be assessed with careful consideration of the risk factors outlined above.12,13 Specifically, it is the failure to take special precautions to minimise the potential for extravasation injury that determines fault. Demonstration of the following would be important: effective securement of the i.v. device, appropriate monitoring of the site, timely recognition of the extravasation, immediacy of intervention and the completeness of documentation.
Severity of injury
Extravasation injuries have been classified into four stages of increasing severity, which are thought to be useful in predicting injury prognosis and in determining the best treatment results.14 The four stages are:
Stage 1: a painful i.v. site, no erythema and swelling, flushes with difficulty.
Stage 2: a painful i.v. site, slight swelling, redness, no blanching, brisk capillary refill below infiltration site, good pulse volume below infiltration site.
Stage 3: a painful i.v. site, marked swelling, blanching, cool to touch, brisk capillary refill below infiltration site, good pulse volume below infiltration site.
Stage 4: a painful i.v. site, very marked swelling, blanching, cool to touch, capillary refill of > 4 seconds, decreased or absent pulse, skin breakdown or necrosis.
Objectively assessing injuries according to these criteria has been recommended both in treatment and in research so that accurate outcome data can be collected. Researchers have suggested that these can be used to guide assessments and interventions. Clifton-Koeppel8 goes further, stating that using a protocol based on these criteria would improve consistency in assessment, increase compliance, decrease the incidence of extravasation and allow for prompt treatment. The author also suggests that stage 4 injuries should be further categorised to include a stage 5 injury that is distinguishable from a stage 4 injury by also including extensive or very deep wounding. However, this extra criterion has not been widely adopted.
There have been attempts to adapt, rather than subdivide, the stages of injury.3 The Infusion Nurses Society adapted the scale by including guidelines3 for the size of the injury and by suggesting that infiltrations involving vesicant solutions should automatically be considered as stage 4 injuries. Other researchers have argued that the Millam guidelines are not appropriate for paediatric populations.3,15 The smaller size of children means that similarly sized injuries (to those seen in adults) are actually much more severe. To counter this, researchers have proposed alternative guidelines.3,15 Amjad et al.3 accomplished this by referring to the number of joints involved, rather than overall size of the injury, to determine scale of injury. Similarly, Simona15 used percentage of the limb affected, rather than measurements, to determine the injury’s grading.
Treatment options
The main objective for treating extravasation injuries is to prevent pain and progression to tissue necrosis, ulceration, and scarring.16 However, there is no consensus on the best approach to management.17–19 The intervention strategies used are normally driven by the type and extent of the injury and by the time interval between injury and intervention. Treatment options are many and varied, but broadly fall under the following categories.
Conservative management strategies
This typically involves elevating the affected limb to reduce oedema by decreasing the hydrostatic pressure in the capillaries. Carers may administer hot or cold dressings. Heat promotes the absorption of extravasated fluids and oedema, whereas cold dressings may limit inflammation. The standard dressing of wounds and administration of analgesics would come under this category of treatment.
Topical treatments
Topical treatments are most often used when an open wound is present. These include nitroglycerin or silver sulfadiazine ointment and dimethyl sulfoxide (DMSO). These attempt to promote a moist wound environment, which, it is argued, reduces healing time, reduces likelihood of infection and prevents scarring.8
Antidotes
Some vesicant solutions may have a particular antidote which can be infused or injected into an affected area. This approach appears to be most often used for treating chemotherapy extravasations. Among the antidotes recommended for use are sodium thiosulfate for mechlorethamine, hyaluronidase for plant alkaloids and dexrazoxane for anthracyclines.20 However, guidelines published by the European Society for Medical Oncology1 indicate that specific antidotes are not commonly used and their effectiveness has been questioned. It should also be noted that the specific antidotes have limited access for use in European countries.1
Hyaluronidase injections
Subcutaneous hyaluronidase injections can be used in an attempt to break down connective tissue and facilitate absorption of the extravasated fluid into the vascular and lymphatic systems. It has been recommended that the administration of these injections should take place within one hour of the extravasation.18
Saline flush-out and liposuction
Both saline flush-out and liposuction are administered with the aim of removing the extravasated fluid before it can cause damage. As such, there is an implicit requirement that these treatments are undertaken as soon as possible. Gault21 has described both techniques, which can be administered alone or together, although various modifications to these techniques have also been reported.
Flush-out techniques typically involve skin incisions being made in the extravasation injury and saline injected into each incision, the aim being that this process will flush out the infusate via the remaining puncture points. The process is sometimes preceded by injection of hyaluronidase to break down the hyaluronic acid in connective tissues, thus aiding infusate dispersal. The procedure is often performed under a local anaesthetic, although a general anaesthetic may sometimes be necessary, especially if liposuction is also to be performed. Liposuction is a minimally invasive surgical technique in which a cannula with side holes is inserted into the wound, and fluid and subcutaneous fat is aspirated out.
Surgery
If less invasive treatments are unsuccessful and necrotic tissue is unresolved after an extended period of time, the next option on the treatment pathway is surgical debridement, or plastic surgery, or both. The purpose of debridement is the removal of necrotic tissue (eschar), which impairs wound healing. It typically involves either a surgical technique (the use of sharp instruments to excise the eschar under general anaesthesia) or an enzymatic approach (which promotes softening of eschar tissue). Once the wound is clean, application of a skin graft or artificial skin may be necessary.
Current guidelines on treatment
Few treatment guidelines have been published, and recommendations are often conflicting.1,8,16,18,19 For example, the saline flush-out treatment, as originally proposed by Gault21 has been described as very effective and to be recommended,8 as having achieved good results,2 as potentially effective but lacking in evidence18 and as not to be recommended as routine management.1 This finding is unsurprising given the inconsistency of the approach to treatment and given that many of the published, peer-reviewed guidelines and reviews that exist are based on limited research evidence.17,19,22,23 Reviews of the area highlight a paucity of good-quality comparative research between treatments for extravasations of cytotoxic drugs. The literature appears even sparser for the management of paediatric populations and for treating extravasation injuries resulting from non-cytotoxic drugs.16,24
Despite published guidelines,2 evidence from surveys suggests there is a lack of consensus on the best course of treatment for extravasation injuries. The lack of consensus is also illustrated by the existence of the many local hospital guidelines on management as indicated by UK survey findings.5 The pattern appears to be replicated internationally, as reported in surveys conducted in the USA25 and Australia and New Zealand.26 A British survey conducted by Wilkins et al.5 found that exposing the wound to the air alone was used for 29% of cases, 43% of cases were treated with saline wash-out (85% of which also included the use of hyaluronidase), 20% were treated with hydrocolloids and 5.5% with hydrogels. A similar survey was conducted in Australia and New Zealand by Restieux et al.26 This study found that limb elevation was used in 63% of cases, saline wash-out in 67%, hyaluronidase in 38% and 27% used a specific antidote. There is a very different distribution of treatments between the two regions, with only the proportion of hyaluronidase use being equivalent. Pettit et al.25 used a sample in the USA to look specifically at hyaluronidase and phentolamine use. They found that only 57% had a procedure for hyaluronidase use and only 29% had a procedure for phentolamine.
Aside from the specifics of the management techniques reported in these surveys, two of the surveys revealed that there appeared to be a significant proportion of centres which did not have a written policy for the treatment of extravasation injuries. Restieaux et al.’s26 survey of 27 NICUs in Australia and New Zealand reported this rate as 35%, whereas Pettit and Hughes’25 survey of nine geographical areas in the USA reported a rate of 27%.
The lack of consensus in sites, and within and between these surveys, is concerning, particularly with regard to the finding in the UK study5 that a substantial minority of cases were being treated solely by exposure to air. However, it should be noted that this study is somewhat outdated, with current NHS practice likely to be different. An up-to-date survey is therefore warranted. Despite this, it is still apparent that policies are largely based on historical practice within hospitals, on prior experience and on expert opinion, rather than on published guidelines.22
Overall aims and objectives of the study
This study aims to begin the process of resolving the uncertainty surrounding which treatments are the best for treating extravasation injuries in babies and young children. Results from a scoping review will determine which treatments are likely to be the most promising, and results from a NHS survey will inform on which treatment approaches are currently used across the NHS and provide opinions about which interventions are most worthy of future research.
