Extravasation and Infiltration Injuries - management in PICU

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This guideline does not cover the extravasation of chemotherapeutic agents which are directly damaging to surrounding cells and require specific antidotes. These should be managed as per the Starship Paediatric Oncology and Haematology Service "Extravasation of Vesicants" Guideline.

Definition

Extravasation - inadvertent administration of a vesicant into the surrounding tissue instead of the intended intravenous pathway. Results in blistering and tissue necrosis and requires immediate attention to limit further injury.

Infiltration - inadvertent administration of an irritant into surrounding tissues instead of the intended intravenous pathway. Results in inflammation and pain but not tissue necrosis. Usually benign but large volumes can lead to nerve compression and compartment syndrome.

Risk Factors

• neonates and small children
• small fragile veins
• poorly secured IV's
• use of metal cannula (ie butterfly needles)
• unconscious/altered mental state/nonverbal child
• poor insertion technique
• multiple venous punctures
• IV placement across areas of flexion (wrist, antecubital fossa)¹

Table 1: High Risk Infusions and Medications (Vesicants)

Hyperosmolar Solutions	Non-Physiological pH	Vasopressors
Fluids: 10-50% Glucose, 3% Saline, TPN, Mannitol Medications: Aminophylline, Ampicillin, Calcium solutions, Diazepam, Digoxin, Lorazepam, Nitroglycerin, Phenobarbitone, Phenytoin, Potassium, Radiographic Contrast, Sodium Bicarbonate	Acidic: Amioderone, Amphotericin, Caffeine, Doxycycline, Gentamicin, Metronidazole, Pentamidine, Promethazine, Vancomycin Alkaline: Aciclovir, Ampicillin, Phenytoin, Thiopentone	Adrenaline Noradrenaline Dopamine Dobutamine Vasopressin Phenylephrine Methylene blue

Non Pharmacological Treatments

Elevation: Recommended for first 48hrs post extravasation.¹ However, caution must be taken if injury secondary to high risk agent as elevation may result in further spreading of agent and subsequent increase in area of damage.

Temperature: Use of warm and cold compresses remains controversial. Warm compresses increase blood circulation and encourage drug dispersal away from affected area but tissue maceration and necrosis has been reported. Cold compresses can induce vasoconstriction and limit damage to surrounding tissue but potentially increase local tissue damage. If used, compresses should be applied proximal to the injury - not directly on the injured tissue. Wet compresses should never be used as this increases the risk of tissue maceration.

Saline Irrigation: Used for severe hyperosmolar extravasations to assist with removal of extravasated material. Evidence for use is limited to case series reports which suggest that early treatment with saline irrigation +/- hyaluronidase results in good long-term functional and cosmetic outcomes.²

Surgical Intervention: Acute decompression of compartment syndrome may be required in severe cases of hyperosmolar extravasation.

Table 2: Grading of Extravasation Injuries (Millam 1988)³

Stage 1	Stage 2	Stage 3	Stage 4
Painful IV site	Painful IV site	Painful IV site	Painful IV site
No erythema	Erythema present	Blanching	Blanching
No swelling	Slight swelling	Marked swelling	Very marked swelling
Flushes with difficulty	No blanching	Cool to touch	Cool to touch
	Brisk capillary refill distal to infiltration site	Brisk capillary refill  distal to infiltration site	Capillary refill > 4 sec*
	Good pulse distal to infiltration site	Good pulse distal to infiltration site	Decreased or absent pulse*
			Skin breakdown or necrosis*

* The presence of any one of these signs constitutes a stage 4 injury

Suggested Management

At first concern of infiltration:

• Stop infusion immediately and aspirate as much back from cannula as possible
• Leave IV cannula in situ
• Assess grade of injury (see Table 2 above)

Stage 1 and 2 Injuries:

• Remove IV cannula
• Elevate limb for 48 hours
• Remove any constricting bands/clothing
• Document injury in clinical notes

Stage 3 and 4 Injuries:

• As above EXCEPT leave cannula in situ as antidote may be required
• Inform charge nurse and registrar - requires urgent medical review as injuries secondary to high risk infusions (Table 1) require individualized management (see below).
• Photograph injury for documentation in clinical notes +/- referral to plastic surgical team
• Log a Risk Monitor Pro Incident Report

Specific treatment for extravasation injuries

Hyperosmolar Agents: Saline Irrigation to dilute and flush out as much of the infiltrated agent as possible. If available, hyaluronidase may be infiltrated into the area immediately prior to irrigation to aid in dispersion of the agent.⁴

Agents with Non-Physiological pH: No specific antidote. Warm compresses and elevation are recommended. Neutralisation should be avoided because this can produce exothermic or gas forming reactions that may worsen tissue injury.⁴

Vasopressors: Warm compressors recommended - apply proximal to the site of injury for 15-20mins at least 4 times daily for first 24-48hrs. Phentolamine injected subcutaneously into the area of infiltration reduces vasoconstriction and local ischaemia. DO NOT use hyaluronidase or cold compressors as this may worsen injury. The use of topical nitroglycerine 2% cream has been reported when phentolamine not available and may be more appropriate as first line treatment for vasopressin and methylene blue extravasations.⁴

Saline Irrigation Technique

• Perform under sterile conditions - topical antiseptic, sterile gloves, drape and dressing pack.
• This is a painful procedure - administer appropriate analgesia prior and infiltrate area proximal to affected area and within the affected area with local anaesthetic - 1% lignocaine.
• Make shallow incisions in the overlying skin with a scalpel or sharp needle 1-2cm apart over affected area.
• Use the white plastic cannula sheath off a large bore angiocath (needle removed) attached to a 20ml syringe filled with 0.9% saline.
• Begin at the center of the affected area (where agent is most concentrated) and gently infiltrate subcutaneous tissue via the skin incisions - fluid should be seen to leak from surrounding incision sites.
• Refill syringe and repeat - 500mls saline washout volume is reported in the literature to give good results.^2,5
• When washout complete - elevate limb to allow further drainage and cover with a sterile non-stick dressing. Wound must be inspected at least Q6H over the next 24hrs.

Table 3: Antidotes

Agent	Dose and Administration	Caution	Mechanism of Action
Hyaluronidase	150unit/ml solution - given as five 0.2ml subcutaneous injections into extravasation site via 25g needle. One injection may be administered via cannula if remains insitu. Total dose = 1ml = 150units6	Most effective if administered within 2hrs, reports of efficacy up to 12hrs post injury.4 Effect lasts 24-48 hrs. Only to be used in conjunction with saline irrigation7	Breaks down connective tissue hyaluronic acid increasing the distribution and absorption of locally injected substances.
Phentolamine	5mg made up to 10ml with 0.9% Saline solution - given as subcutaneous injections into extravasation site and via cannula if remains i nsitu Dose = 0.1-0.2mg/kg, max dose 5mg.4,6	Effective up to 12 hrs post injury.4  Systemic absorption may result in tachycardia and hypotension.	Competitive α-adrenergic blockade. Reverses the alpha mediated vasoconstriction properties of vasopressors.
Topical nitroglycerin 2%	1 inch strip4 Apply directly to affected area.	Tachycardia and hypotension from systemic absorption. Use with extreme caution if cardiovascular instability.	Vasodilatation of capillaries to improve blood flow and reduce ischaemia.

Refer to Middlemore Plastic Surgical team: injuries secondary to calcium solutions, any injury with signs of necrosis/skin breakdown or compromised perfusion and all injuries where the area of extravasation involves a joint.

Discuss case with on-call plastics registrar - via Middlemore Hospital call center

Email clinical details and photographs to: Plasticreferrals (Plasticreferrals@middlemore.co.nz)

References

1. Martin SM. Extravasation Management of Nonchemotherapeutic Medications. Journal of Infusion Nursing 2013;36(6):392-396.
2. Gopalakrishnan PN, Goel N, Banerjee S. Saline irrigation for the management of skin extravasation injury in neonates. Cochrane database Syst. Rev. 2012
3. Millam DA. Managing complications of i.v. therapy. Nursing 1988;18(3):34-43
4. Reynolds PM, Maclaren R, Mueller SW, Fish DN, Kiser TH. Management of extravasation injuries: A focused evaluation of noncytotoxic medications. Pharmacotherapy 2014;34(6):617-632.
5. Harris PA, Bradley S, Moss AL. Limiting the Damage of Iatrogenic Extravasation Injury in Neonates. Plastic and Reconstructive Surgery. 2001 107(3):893-894
6. Le A, Patel S. Extravasation of noncytotoxic drugs: A review of the literature. Ann. Pharmacother. 2014;48(7):870-886.
7. New Zealand Formulary For Children release 35-1 May 2015 | ISSN: 2350-2916