This document discusses extravasation, which is the unintentional leakage of drugs or substances out of blood vessels into surrounding tissue. It describes different types of extravasations based on the properties of the leaked substance. It identifies numerous risk factors for extravasation related to patients, medications, devices, clinicians and procedures. Symptoms and a grading system for extravasations are provided. The document outlines extensive guidelines for the prevention, assessment, management and treatment of extravasations with various antidotes and approaches depending on the substance extravasated. It emphasizes the importance of education for patients and clinicians to prevent and properly handle extravasations.

1. Dr.Rajni Sharma
Mahamana Pandit Madan Mohan
Malviya Cancer Centre, Varanasi
Department of Atomic Energy,
Government of India
Dealing with Extravasation

2. The unintentional instillation or
leakage of a drug or substance
out of a blood vessel into
surrounding tissue.
Extravasation:

3. Non-irritant (neutrals)
Irritant
Irritant with vesicant properties
Vesicant
1.DNA binding vesicants(i.e, dactinomycin,doxorubicin
etc.)
2.DNA non-binding vesicants(i.e, vincristine,vinblastine
etc.)
3.Cisplatin at concentrations > 0.5 mg/mL

4. Risk factors:
Patient related risk factors:
 small and/or fragile veins (e.g. elderly and children)
 hard and/or sclerosed veins
 limited vein availability (due to lymph node dissection, lymphedema
 obesity in which peripheral access is difficult
 patient movement
 predisposition to bleeding, increased vascular permeability or coagulation abnormalities
 altering sensory perception that may impair patient’s ability to detect sensory changes at the
site of administration
 diseases with impaired or altered circulation (e.g. advanced diabetes, Raynaud syndrome,
superior vena cava syndrome)
 impaired communication (e.g. non-English speaking patients, patients with communication
difficulties, sedation, young children)
 disseminated skin disease (e.g. eczema, or psoriasis).

5. Medication/ infusion related risk factors:
Drug related risk factors:
vesicant potential of drug
multiple vesicants within a treatment protocol
concentration of drug
volume of drug administered
chemical properties of drug (e.g. pH or osmolarity).

6. Device and access related risk factors:
 high flow pressure (e.g. infusion pump)
 long infusion period
 repeated use of the same vein for vesicant administration
 multiple attempts at cannulation
 unfavourable cannulation site
 choice of equipment (e.g. cannula choice, size, steel “butterfly” needle)
 inadequate dressing or poor fixation of central venous access device (CVAD) or intravenous
cannula (IVC)
 deeply implanted port, leading to wrong placement of needle or dislodgement of needle
 backflow secondary to fibrin sheath or thrombosis in CVAD
 CVAD damage, breakage or separation
 displacement or migration of CVAD catheter from the vein.

7. Clinician related risk factors:
untrained or inexperienced staff in vascular
access and the management of antineoplastic
drugs
interruption or distractions during drug
administration.

8. Symptoms and signs
 patient complains of burning, stinging, pain or discomfort
 patient complains of thoracic pain
 evidence of swelling, oedema, erythema, leakage at the site
 absence of free flow of infusion
 change in infusion flow i.e. slow or sluggish
 loss of blood return or change in blood flow
 increase in resistance when administering IV bolus drugs.
 Late symptoms of an extravasation injury include inflammation,
induration and/or blistering.

9. Investigations:
Important assessment parameters include:
drug extravasated, dose, volume
position and size of injury
amount and type of exudate
presence of swelling, oedema
extent and spread of erythema
pain.
**Assessment should be ongoing to allow for the early detection and management of skin changes such as ulceration
and necrosis

10. Issues specific to CVAD extravasation
 In the event of a suspected extravasation from a CVAD, imaging techniques such
as X-ray, CT or MRI may be performed.
 Linogram/ portogram may be performed to ensure that there is no fracture in
the catheter of the CVAD

11. Grading:
GRADE Infusion site extravasation
I
Painless oedema
II
Erythema with associated symptoms (e.g. oedema, pain, phlebitis)
III
Ulceration or necrosis: severe tissue damage; operative intervention
IV
Life-threatening consequences; urgent intervention indicated
V
Death

12. MANAGEMENT:
Prevention : Multidisciplinary approach should be taken to
mitigate risks of extravasation.
Patient education
1. identify high risk patients
2. ensure there are no barriers to effective communication
3. educate patients and caretaker to monitor and immediately
report symptoms such as pain, burning, stinging, swelling, or
erythema during and after administration of cytotoxic drugs.

13. Clinician training:
do not inject against resistance
administration and management of antineoplastic
drugs by trained and accredited health professionals
insertion, access and management of CVADs and IVCs
by trained and accredited health professionals
ensure knowledge and access to current literature in
extravasation management

14. Appropriate vascular access
identify most appropriate site for IVC insertion
infusion sites should be selected in the following
order of preference: forearm (basilic, cephalic, and
median antebrachial), dorsum of hand, wrist,
antecubital fossae
avoid sites with sclerosis, thrombosis, scar formation
or previously irradiated areas
if venous access via an IVC proves difficult, or
inadequate, consider a CVAD.

15. Safety procedures
When accessing and before drug administration, ensure
patency of the CVAD or IVC by checking
1.for blood return
2.no resistance is felt when flushing with 0.9% sodium
chloride or other compatible fluid
3.intravenous infusion flows freely
Monitor the patient and CVAD or IVC site regularly for the
appearance of symptoms such as swelling, pain, erythema
or a change in the infusion rate
Flush with 10 to 20 mL of sodium chloride 0.9% or other
compatible fluid between different drug infusions, checking
for signs of extravasation.

16. Device selection:
do not use winged steel infusion devices for cannulation
(“butterfly” needles), flexible cannulas should be used
use the smallest adequate and appropriate size cannula
in the largest available vein
ensure the CVAD or IVC is stabilised and secure with a
transparent dressing to allow the site to be visualised
if unable to confirm patency of CVAD, do not proceed
without a full review of the CVAD and radiologic
confirmation of patency
if unable to confirm patency of IVC, insert a new IVC.

17. Vesicant administration:
 administer vesicants via a newly inserted IVC
 administer vesicant drugs before other antineoplastic drugs (unless
recommended otherwise by protocol)
 if there is more than one vesicant drug, administer DNA binding drugs
followed by non DNA binding drugs e.g. anthracyclines followed by vinca
alkaloids
 do not use infusion pumps to administer vesicants (unless recommended
otherwise by protocol or institutional guidelines)
 for bolus injections, administer concurrently with a fast running infusion of
0.9% sodium chloride or other compatible fluid
 for bolus injections, patency and blood return should be checked
regularly as per local institutional guideline
 for infusions (mini bag), patency and blood return should be checked
regularly as per local institutional guidelines

18. It is recommended that an extravasation
kit containing instructions, materials and
antidotes, is kept in each patient care area where
chemotherapy is administered.

20. In the event of an extravasation, regardless of
the nature of the drug, the initial steps are as
follows:
STOP the injection or intravenous
infusion immediately.
LEAVE the venous access device (VAD)
in place.
ASPIRATE any residual drug from the
VAD using a sterile syringe.
PLAN

21. •CALL for assistance - notify medical officer, pharmacist and/or a
senior nursing officer.
•COLLECT the extravasation kit.
•ASSESS the affected area for the presence of symptoms e.g.
erythema, swelling, burning, pain and TRACE the affected area
with a marker pen.
•PHOTOGRAPH the area.
•REMOVE the IV device or port needle. Do not apply pressure. If
a central line is in situ this should remain in position - refer to a
medical officer for further instructions.
•ELEVATE the limb if it provides comfort to a patient
•INITIATE appropriate drug specific management measures as
per protocol.
•ADMINISTER pain relief if indicated.
•REFER to a plastic surgeon or other specialist surgeon
(according to individual case and site of extravasation) if
clinically indicated.

22. Antidotes

23. Dimethyl sulfoxide (DMSO) 99% solution
 is used in the management of amsacrine, dactinomycin, daunorubicin, doxorubicin, epirubicin,
idarubicin, mitomycin extravasation
 should be applied as soon as possible after extravasation has occurred (ideally within 10–25
minutes)
 DO NOT use with liposomal doxorubicin as application may cause release of active drug from
the liposomes
 DO NOT apply DMSO 99% solution to wet skin as a chemical burn can result
 side effects of DMSO 99% solution include itching, erythema, mild burning and a
characteristic 'garlic' breath odour.

24. Hyaluronidase:
 is the recommended antidote for the extravasation of vinblastine, vincristine,
vindesine, vinorelbine, vinflunine
 acts by promoting the dispersion of extravasated drug
 has been reported to produce positive outcomes for paclitaxel extravasation;
if used for a paclitaxel extravasation, no compress is recommended.

25. Dexrazoxane:
 must be administered within 6 hours of an extravasation
 has shown efficacy in preventing anthracycline wound formation
 refer to institutional guidelines for obtaining and administration procedures
 may cause additive myelosuppression effects with concomitant administration, patients
should therefore be closely monitored.

26. Cold compresses
 The topical application of cold compresses is recommended for the management
of extravasation of drugs classed as vesicants, or irritants with vesicant properties,
with the exception of the vinca alkaloids (vinblastine, vincristine,
vindesine, vinorelbine, vinflunine) and oxaliplatin.
 **In the case of an oxaliplatin extravasation, the use of a cold compress may
exacerbate sensory neuropathy.

27. Intermittent cooling is thought to:
•cause vasoconstriction, localising the
extravasation
•reduce local inflammation and pain
•decrease cellular uptake of drug.
Instructions for use:
•cover a cold pack with a waterproof covering
and place over the affected area
•leave for 15 to 20 minutes (no moisture
should come in contact with the patients skin)
•apply every 6 hours for 48 hours.

28. Warm compresses
 Topical application of warm compresses is recommended for use in vinca alkaloid
(vinblastine, vincristine, vindesine, vinorelbine, vinflunine) extravasations because:
 the application of warmth may decrease local drug concentration, increasing the
blood flow which results in enhanced resolution of pain and reabsorption of local
swelling
 the application of cold has been shown in animal models to increase the risk of
tissue damage
 the application of warmth has been reported to be synergistic with
hyaluronidase.

29. Instructions for use:
•cover a warm pack with a
waterproof covering and place over
the affected area
•leave for 15 to 20 minutes (no
moisture should come in contact with
the patient's skin)
•apply every 6 hours for 48 hours
•refer to your local institutional
guidelines on using warm packs.

30. Limb mobilisation
 A study evaluating the efficacy of limb elevation post an infiltration injury found
that a 10 cm elevation of the extremity made no difference in the rate of fluid
reabsorption.
 Movement should be encouraged to prevent adhesion of damaged areas to
underlying tissues.
 Elevate the limb if it provides comfort to a patient.

31. Referral to a plastic surgeon or other specialist surgeon (according to
individual case and site of extravasation) is recommended.
Surgical intervention

32. Follow up care
 Patient to monitor the affected area daily for any skin changes or breakdown, and to
notify medical team immediately of any changes.
 Careful monitoring by a healthcare professional is recommended; the length of
monitoring should be at the advice of the medical officer, and will depend on the
cytotoxic drug extravasated and the clinical course of the injury. Consider daily or
second daily review for the first week, and then weekly until complete resolution of
symptoms.
 It is important to note that early vesicant extravasation signs or symptoms can be
subtle, and not always evident until several days or weeks later. Regular patient
review is recommended.
 Patients should be informed about the follow-up policy before leaving the treatment
area.
 Take photographs at follow up appointments.
 Community nurse or GP referral may be required for follow up care.

33. Patient Education
 keeping the extremity still when receiving vesicant drugs or irritants with vesicant
properties via an IVC
 immediately reporting any pain, swelling, redness, discomfort, burning or stinging.
 measures for general management and reducing further damage:do not rub or scratch
the area
1. do not wear tight clothing on area
2. avoid occlusive dressing over the area
3. protect the area from sunlight
4. raise the affected arm on a pillow if it provides comfort
5. move/exercise the affected arm gently
6. do not use creams or lotions on affected area without speaking with your doctor or
nurse

34. •equipment required to care for the injury
•how to check the affected area daily and report
increase in pain or any skin changes (such as
change in colour, temperature or breakdown)
•how to monitor temperature and seek urgent
medical attention if temperature 38°C or higher
•contact numbers for during and after hours
•when to contact clinic or present to emergency
•dates and times of follow up appointments
•the importance of follow up.

35. REFERENCES:
Payne, AS et al. 2018. "Extravasation Injury from Chemotherapy and other non-
antineoplastic vesicants. In UpToDate (accessed 2019)
2
Mader, I., P. Furst-Weger,. et al. 2010. "Extravasation of Cytotoxic Agents: Compendium for
Prevention and Management." Version 2 Springer Wien New York
3
Perez Fidalgo, J.A., L. Garcia Fabregat, A. Cervantes, et al. 2012. "Management of
Chemotherapy Extravasation: ESMO-EONS Clinical Practice Guidelines". Ann Oncol 23
Suppl 7:vii167-173
4
Hospira Australia Pty Ltd. DBL Cisplatin Product Information, version 6.0. Date of most recent
amendment: 15 September 2017
5
Sauerland, C., C. Engelking, R. Wickham, et al. 2006. "Vesicant extravasation part I:
Mechanisms, pathogenesis, and nursing care to reduce risk." Oncol Nurs.Forum.
33(6):1134-1141.
Read abstract
6
Dougherty, L., Lister. 2007.The Royal Marsden Hospital Manual of Clinical Nursing Procedures.
7th Edition. Wiley-Blackwell.

36. Thank you