EXTRAVASATION INJURIES

Christian Dumontier, MD, PhD

Centre de la Main, Guadeloupe
To be downloaded at www.diuchirurgiemain.org
 DEFINITION

• The inappropriate or accidental in ltration of a

medicinal product from a displaced intravascular
cannula into the perivascular/subcutaneous tissues
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 THE FREQUENCY
• Very very frequent in daily practice but rarely a problem as far as the
agent has no or little toxicity

• From11% to 58% in children receiving intravenous uids

• Incidence of 0.43% in iodinated contrast media, has increase to

0.5% to 0.9% with the use of the power injectors.

• Extravasation rates of 0.01% to 6.5% in patients receiving

chemotherapy.
Khan MS, Holmes JD. Reducing the morbidity from extravasation injuries. Ann Plast Surg 2002;48:628 – 632.
Wilkins CE, Emmerson AJ. Extravasation injuries on regional neonatal units. Archives of Disease in Childhood. Fetal and
Neonatal Edition 2004;89(3):F274-5.
Langstein HN, et al. Retrospective study of the management of chemotherapeutic extravasation injury. Ann Plast Surg.
2002;49:369–374.
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 THE PROBLEM ?
HOW SEVERE IS THIS COMPLICATION ?
• The degree of tissue damage depends on the
volume, toxicity of the agent, site of the
cannula, and patient factors

• Mostly problematic with compounds that have

irritant or vesicant properties.

• Compartment syndromes have also been reported

 PATIENTS’ RELATED FACTORS
• Extremes of age
• Vascular compromise
(peripheral vascular
disease, venous
insuf ciency and
lymphatic obstruction)
• Peripheral neuropathy
Parenteral nutrition extravasation from Paquesoone L et al. L’extravasation chez l’enfant, prise en charge en urgence. Ann Chir Plast
2016; 61:598-604
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 MECHANISM OF INJECTIONS
• Power injectors and metallic needles as opposed to plastic cannulae
increases the risk of extravasation.
• Infusion sites including peri-articular areas and the lower limb are more
prone to dislodgement due to movement;
• Placing the cannula near tendons or nerves increases the risk of severe
complications.

• Multiple previous venepunctures

especially moving distally along a
vein can compromise venous wall
integrity.
 THE INJECTED DRUG
• Physical injuries • Chemical injuries

• Volume • Cytotoxicity

• PH • Concentration of the
extravasant
• Osmolality

• Vasoactive properties
PH VALUES

• Agents with
pH values
outside 5.5–
8.5 are
particularly
harmful to
tissues
•
 OSMOLALITY
• Hypertonic (cell implosion) or Hypotonic (cell
explosion)
➡ Glucose solutions (10% or greater).
➡ Sodium bicarbonate preparations (above
1.8%).
➡ Potassium/sodium chloride, calcium gluconate,
magnesium sulphate, mannitol infusions.
➡ Total parenteral nutrition preparations (with
osmolalities averaging 650 mOsm/L).
➡ Ionic, high osmolality radiological contrast
media.
Extravasation of D50
Samson et al.
VASOCONSTRICTIVE/DILATORY PROPERTIES

• 318/325 events resulted from peripheral IV administration.

• 204/318 local tissue injury and 114 extravasation of vasopressor solution, 75.4% did not result in any tissue
injury.

• 179/204 skin necrosis, 5/204 tissue necrosis, 20/204 gangrene

Ousmani, OM et al. A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral
intravenous catheters and central venous catheters. Journal of Critical Care 30 (2015) 653.e9–653.e17.
 THE INJECTED DRUG
• Volume PH • Medications are broadly
divided into vesicants,
• Osmolality, exfoliants, irritants,
in ammatory, and
• Vasoactive properties
neutral agents in
• Concentration of the descending order of
extravasant, cellular toxicity and type
of reaction/tissue damage
• Cytotoxicity, they cause
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 CLASSIFICATION OF EXTRAVASANT

• Vesicants produce local tissue necrosis both within and outside the venous
system (DNA binding and non-DNA binding)

• Exfoliants cause in ammation and skin shedding, but are less likely to cause
subcutaneous tissue damage.

• Irritants cause pain and in ammation at the administration site and along
the vein, but rarely result in necrosis.

• In ammatory agents produce a mild-to-moderate in ammatory reaction.

• Neutral or inert agents cause no in ammation or damage.

Hahn JC, Schafritz AB. Chemotherapy Extravasation Injuries. JHS 2012; 37A; 360-362.
Allwood M, Stanley A, Wright AP. The Cytotoxics Handbook. 4th ed. Oxford: Radcliffe Medical Press; 2002.
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 VESICANTS: SOME MORE
DETAILS
• Vesicants produce local tissue necrosis both within and outside the venous system.

• Chemotherapeutic vesicants are further classi ed into DNA binding and non-DNA
binding.

• DNA binding drugs (epirubicin, mitomycin, doxorubicin, daunorubicin, idarubicin) set-

up a continuous cycle of tissue damage by cellular DNA–medication complexes, which
are taken up by adjacent healthy cells via endocytosis propagating tissue damage.

• Non-DNA−binding agents (vinblastine, vinorelbine, vincristine) are metabolized and

neutralized more easily in the tissues and result in less extensive injuries

• Extravasation with liposomal encapsulated anthracyclines can be treated in a less aggressive

manner because no extensive tissue necrosis has yet been recorded in the literature
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 MAKING THE DIAGNOSIS
• Technical problems:

• Induration, swelling or leakage at the injection site No back ow of

blood

• Resistance on the syringe plunger during administration.

• The free owing infusion slows or stops.

• An infusion is not owing freely.

• Patients complains
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 CLINICAL SIGNS OF EXTRAVASATION

• Patient complains of burning,

stinging pain or any other
acute change at the injection
site.

• Erythema at the injection site

• Flare reactions and venous

spasm

Onesti M et al. Chemotherapy Extravasation Management: 21-Year Experience. Ann. Plast. Surg. 2017;79(5):450-457.
 DIFFERENTIAL DIAGNOSIS
• Local hypersensibility reaction (asparaginase,
bleomycin, melphalan, cisplatin): pain redness and
prurit at the injection site

• Thrombophlebitis of the vein

• Allergic reaction with doxorubicin with late pain of

the injection site and sometimes ulceration.
 THE TREATMENT OF
EXTRAVASATION INJURIES
• Prevention is by far • Classi cation of the severity
the most important • Conservative measures

• Local treatment

• Antidotes

• Surgery
Goutos I et al. Extravasation injuries: a review. JHSE 2014, 39(8) 808–818.
Onesti M et al. Chemotherapy Extravasation Management: 21-Year Experience. Ann. Plast. Surg. 2017;79(5):450-457.
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PREVENTION OF EXTRAVASATION

• Trained personnel
• Patient education and co-operation
• Recognize patients at risk:
• Patients with altered circulation or smaller veins
(Raynaud’s disease, diabetes, peripheral vascular disease).
• Patients with SVCO (superior vena cava obstruction)
• Elderly patients with fragile veins and skin
• Altered mental status
PREVENTION OF EXTRAVASATION
• Cannulation site
• Recent cannulation site
• Local warming (dilate veins)
• Flexible cannulas
• Avoid cannulas over joint sites (inner wrist, anticubital fossa and
the dorsum of the foot)
• Previous radiation injury, lymphedema,
• Multiple attempts of cannulation
• Infusion pumps should have alarm on
WHAT TO DO IN EVERY CASE
• Keep the cannula in place (to aspirate)

• Mark the extravasated area to follow-up

its extend

• Elevate the limb to minimise swelling

• Encourage mobilisation

• Take photos

• Follow the protocols that should be

available - have an extravasation kit
available
Reynolds BC. Neonatal extravasation injury: case report. Infant 2007;3(6):230-2.
Onesti M et al. Chemotherapy Extravasation Management: 21-Year Experience. Ann. Plast. Surg. 2017;79(5):450-457.
 WHAT TO DO NEXT

• Adapt treatment to:

• The toxicity of the product

• The volume

• The patient
 THE VOLUME IN NEUTRAL
AGENT
• Signi cant volume

• Results in pain, compression of neuromuscular structures, loss of skin

circulation and/or development of compartment syn- drome,

• Emergency intervention

• Removal of extravasant [ « squeeze » method or liposuction]

• Excision of the affected tissue

• Fasciotomies
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 SPECIFIC AGENTS

• Classify the severity (neutral,

irritant, vesicant)

• Know the « necrosis

interval »

• Adapt treatment to the

type of drug
 CLASSIFICATION OF SEVERITY FOR
VESICANTS

• Mild: Minimal volume of an irritant or vesicant causing little pain/

swelling and no erythema or blistering.

• Moderate: Small volume (up to 5 ml) of extravasation causing

a local in ammatory reaction (less than 10 cm diameter),
moderate tenderness, with or without erythema but no blistering.

• Severe: Larger volume extravasation of typically vesicant

infusions resulting in extreme pain, marked swelling, erythema and
often blistering.

Loth TS, Eversmann WW Jr. Extravasation injuries in the upper extremity. Clin Orthop Relat Res. 1991, 272: 248–54
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 THE NECROSIS INTERVAL
• Delay during which a
surgical intervention could
prevent de nitive injury.

• 4-6 hours (vasopressors)

• 6 hours (radiological
contrast)

• 72 hours
(chemotherapeutic agents)
Loth TS, Eversmann WW Jr. Extravasation injuries in the upper extremity. Clin Orthop Relat Res. 1991, 272: 248–54
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 SOME EXAMPLES

• Contrast media extravasation

• Neutral or irritant drugs extravasation

• Vesicants extravasation
 WHAT TO DO
(CONTRAST MEDIA)

• CT agents are more at risk

Roca-Sarsanedas J et al. Topical treatment of tissue damage due to extravasation of iodinated contrast using thermal compresses. Journal of
Tissue Viability 31 (2022) 135–141.
Sbitany H, et al. CT contrast extravasation in the upper extremity: strategies for management. Int J Surg. 2010, 8: 384–6.
Wang CL, Cohan RH, Ellis JH, et al. Frequency, management, and outcome of extravasation of nonionic iodinated contrast medium in 69,657
intravenous injections. Radiology 2007;243: 80-7.
 WHAT TO DO
(CONTRAST MEDIA)

• Cut-off volume is ≈150 ml

• In most cases topical care is

suf cient (97.4% no or
minimal adverse effects; 2.2%
moderate, 0.4% severe)

• Dry heat seems to be

superior to cold.

Roca-Sarsanedas J et al. Topical treatment of tissue damage due to extravasation of iodinated contrast using thermal compresses. Journal of
Tissue Viability 31 (2022) 135–141.
Sbitany H, et al. CT contrast extravasation in the upper extremity: strategies for management. Int J Surg. 2010, 8: 384–6.
Wang CL, Cohan RH, Ellis JH, et al. Frequency, management, and outcome of extravasation of nonionic iodinated contrast medium in 69,657
intravenous injections. Radiology 2007;243: 80-7.
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 WHAT TO DO (NEUTRAL OR
IRRITANTS)
• Conservative treatment mostly
effective

• Pain relief

• Application of ice: 15 mn, 4 times/

day for 3 days

• Dressings with serial assessment in

the outpatient clinic.
Loth TS, Eversmann WW Jr. Extravasation injuries in the upper extremity. Clin Orthop Relat Res. 1991, 272: 248–54
Goutos I et al. Extravasation injuries: a review. JHSE 2014, 39(8) 808–818.
 WHAT TO DO (VESICANTS)
• Apply heat or cold

• Cold: cause vasoconstriction and

minimise the spread of the drug from
the initial injury allowing time for local
vascular and lymphatic systems to
disperse the agent.

• Heat: cause vasodilation, increasing

drug distribution and absorption and
thus aiding in the dispersal of the drug
from the injury site. Heat is used in
non-DNA binding drug extravasations
 WHAT TO DO (VESICANTS)
• Use speci c antidotes
• Dimethylsulfoxide (Anthracycline). DMSO enhances
skin permeability (facilitates systemic absorption of
the vesicant). Has free radical scavenging properties.
• Sodium thiosulphate is thought to have a direct
inactivation effect on chlormethine (mustine)
• Dexrazoxane (Savene®) is licensed for use in
anthracycline extravasations
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 WHAT TO DO (VESICANTS)

• Use non-speci c antidotes: Hyaluronidase

• (frequently associated with surgical means)

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 WHAT TO DO (VESICANTS)
• The role of the surgeon:

• Stab and squeeze,

• Flush-out technique,

• Surgical debridement

• NPWT.
 STAB AND SQUEEZE

• Multiple needle puncture

• Gentle squeezing of the

zone

Chandanvasu et al. A new method for the prevention of skin sloughs and necrosis secondary to intravenous in ltration. American
Journal of Perinatology 1986;3(1):4-5.
Onesti M et al. Chemotherapy Extravasation Management: 21-Year Experience. Ann. Plast. Surg. 2017;79(5):450-457.
Dyonissou D et al. The wash-out technique in the management of delayed presentations of extravasation injuries. J Hand Surg
Eur Vol. 2011 Jan;36(1):66-9.

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 FLUSH-OUT

• Under local (or general) anaesthetic

• In ltration with hyaluronidase

• As soon as possible: better within 6 hours, may be

ef cient up to 24 hours.

Gault DT. Extravasation injuries. Br J Plast Surg 1993;46:91- 6

Giunta, R. Early subcutaneous wash-out in acute extravasations [Letter].Annals of Oncology 2004; 15: 1146.
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 FLUSH-OUT
• Five or six small stab incisions
around the area of extravasation
injury

• Use an in ltration cannula, (like in

liposuctio,n) and 500mls of saline or
compound sodium lactate
(Hartmann’s solution), inject
20-30mls at a time, through each
incision, and allowing it to drain out
of the other incisions.

• Apply a layer of Jelonet and Betadine

soaked gauze and elevate the limb

Raveendran S et al. Multiple Stab Incisions and Evacuation Technique for Contrast Extravasation of the Hand and Forearm. J Hand Surg Am.
2019;44(1):71.e1-e5
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 NWPT

• May be use as a sole treatment or an adjunct

• Its de nite place is yet to be de ned

Tiwari VK. The ef cacy of VAC therapy on chemotherapeutic extravasation ulcers: an experimental study. Indian J Plast Surg.
2014;47(3):400–401.
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SURGICAL EXCISION AND
IMMEDIATE COVERAGE

• Dif cult to appreciate the extent

of the injury
Fascio-cutaenous ap
(Onesti 2017)
• Some series reported good
results

Napoli P et al. Surgical Treatment of Extravasation Injuries. Journal of Surgical Oncology 2005;91:264–268
Onesti MG, Dessy LA, Fino P, Scuderi N. Use of Integra® dermal substitute in the treatment of complex wounds caused by
antiblastic extravasation injury. J Plast Reconstr Aesthet Surg. 2011 Feb;64(2):e57–e59.
Onesti M et al. Chemotherapy Extravasation Management: 21-Year Experience. Ann. Plast. Surg. 2017;79(5):450-457.
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LATE ROLE OF THE SURGEON

• Reconstruction while necrosis

has appeared

• Skin graft, NPWT, aps,…

which are part of the hand
surgeon armamentarium
6 weeks post vesicant extravasation
From Hahn et al.
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 CONCLUSION
• All extravasations should be treated as a medical
emergency

• The degree of tissue damage depends on the volume,

toxicity of the agent, site of the cannula, and patient
factors

• Mostly problematic with compounds that have irritant

or vesicant properties.
Proposed algorithm