National Extravasation Protocol for Cancer
Chemotherapy: A 10 step plan.
Phase One – COOL & CALM
1. Stop the injection / infusion – Apply ColdA
2. Disconnect IV tubing – Leave cannula in situ - ‘Mark the Area’ with non
soluble markerB.
3. V.L.T. assessmentC – Volume : Location : Time since occurrence.
4. Seek Expert Advice and plan management strategyD
5. Attempt AspirationE – Including if local facilities & expertise are available the
‘Flush Out’ technique.
6. Administer symptomatic treatment(s)F
Phase Two – LOCALISE & NEUTRALISE
7. With intermittent coldG applied, attempt neutralisation if antidote exists and its
application is appropriate to the individual clinical situationH.
8. Warm area to body temperature and continue antidotes if chronic application
is applicableI.
Phase Three – DILUTE & DISPERSE
9. Administer subcutaneous hyaluronidaseJ +/- fluidK, and warm the area to
increase local blood supply and aid dispersionL.
Phase Four – Report and Learn
10. Document the incident and action taken in the patient’s notes - Report the
incident through both local and national schemes – Agree follow up and on
going symptomatic and specific management as appropriate – Photograph
the injury, acutely and at follow up.
Notes: These notes are supported by 6 appendices: –
Appendix 1. Definitions as used in the protocol
Appendix 2. Flow chart version of the protocol
Appendix 3. Details on the techniques mentioned in the protocol
Appendix 4. Drug specific treatment information
Appendix 5. Current classification table for chemotherapy agents
Appendix 6. Example of the new, version 6 of the green card reporting forms for
peripherally and centrally administered chemotherapy
A. This is in the form of a flexible cold pack, such as those used for sports
injuries, it should not be applied directly to the skin, i.e. wrap in a pillow case
or tea towel.
B. It is important to palpate the area and establish EITHER the size of the
subcutaneous fluid pocket in a Type I extravasation; OR the boarders of the
‘soggy, spongy’ tissues in a Type II extravasation. These areas should be
marked NOT the extent of the local reaction.
C. V.L.T. Estimate the volume of the drug extravasated, Table 1 below may help
in conjunction with measurements of the area measured in Note B, the
practioner also needs to decide whether the volume is made up of a single
drug or multiple drugs, and if so which drugs these are, and how much of the
extravasated volume is made up of ‘carrier solution’.
Location is important as certain areas are more able to accommodate larger
volumes of fluid, e.g. the forearm, the more accommodating the compartment
into which the extravasation has occurred, the more difficult it is to estimate
the volume and the greater the risk of compartment syndrome developing.
Time of the incident relative to the time of detection give an estimation of how
much ‘natural’ diffusion will have taken place, i.e. the longer the time the
greater the diffusion the more difficult it is to treat. Therefore all extravasation
injuries should be treated as soon as detected, to minimise damage and
maximise the chance of a successful outcome.
Table 1: Approximate volume of material extravasated in relation to diameter
of the injury and the level of intervention which may be appropriate.
Volume
Approximate
Management
Diameter*
0.1ml to 1.25ml
Up to 17mm
Watch and Wait
1.25ml to 2.5ml
17 to 30mm
Topical low impact interventions
Greater
than
Greater
than
Full
blown
no
holes
bared
2.5ml
30mm
interventions
* If diameter is measured within 15minutes of the acute extravasation so that
minimal tissue diffusion will have occurred. Measurement should not include the
inflamed surrounding tissue see Note B. above
D. The trust or Network should appoint an extravasation coordinator; this
individual should work with the local medicines information service to provide
locally applicable advice. However if this individual is not available or if further
advice is required; try the extravasation website or Andrew Stanley on 07976
960 474.
E. Aspiration particularly for type II extravasation injuries is notoriously difficult,
and produces limited success, if the local policy is to perform the wash out
technique then it should be employed at this point in the pathway, patients
should be returned to the protocol at stage three is dispersal of the residual
wash out material is required or stage four to ensure the incident is correctly
reported and followed up.
Aspiration should be attempted using the ‘pin cushion’ technique, this
technique is painful and distressing to the patient, therefore the marked area
should be covered in Amitop or Emla cream and left for 30 minutes whilst
topical anaesthesia is achieved.
F. Symptomatic Management; this is about settling the local ‘cytokine’ cascade
that has been triggered by the injury; the exact symptom management will
depend on the extent and location of the injury and the nature of the patient.
However practioners should considered topical and local treatments first,
followed by central and oral interventions second, and intravenous and
systemic treatments third and last, and only if required. Table 2 below details
some of the topical, oral and intravenous interventions which have been used
in extravasation injuries:
Table 2: Topical Oral and Intravenous interventions to consider in the
symptomatic management of an extravasation injury
Agent
Topical
Hydrocortisone cream 1%
Mode of Action
Anti-inflammatory
Crotamiton 10% cream(Eurax)
Eurax-Hydrocortisone cream
Heparinoid
(Hirudoid)
0.3%
cream
Topical
NSAID’s
Ibuprofen or Diclofenac)
(e.g.
Oral and central
Sodium Cromoglicate
Ibuprofen
(or
alternative
Anti-pruritic
Combination
of
above
Improve
local
circulation; used in
the dispersal phase
of an extravasation
injury.
Local pain relief
Prevent
degranulation of Mast
cell
and
limit
histamine release
Systemic pain relief
Dose & Schedule
PRN in
initial
management then
TDS
TDS
TDS
QDS
500mg stat., may
continue
at
100mg QDS if
clinically
beneficial
400mg
stat
NSAID)
Chlorpheniramine
Paracetamol: can be escalated
to Co-codamol 8/500’s and
then to 30/500’s
Morphine immediate release
(Oramorph 10mg in 5ml or
Sevredol 10mg tablets)
Anti-histamine
to
‘Mop up’ / ‘Dampen
down’
released
histamine.
Adjuvant to the
ibuprofen or for
level 2 pain relief
Level 3 pain relief
Systemic – Intravenous or subcutaneously
Diamorphine
Sever, acute pain
Hydrocortisone
Chlorpheniramine
Anti-inflammatory
Alternative
fast
acting
antihistamine.
Alternative to 8mg
po loading dose
followed
by
400mg tds
8mg stat followed
by 4mg QDS
2 - QDS max 4g
of paracetamol in
24hours.
10
or
20mg
immediately
followed by 10mg
QDS prn
10mg IV, IM or s/c
prn
200mg IV stat
10mg IV stat
G. Intermittent cold is simply the use of the cold pack to restrict the local blood
supply whilst the antidote, see Table 3, is instilled and for the following
24hours whilst it is allowed to work and or if repeated instillations of the
antidote are required, this dose NOT apply to systemically administered
intravenous antidotes, only those applied topically.
H. The appropriate use of any antidotes should be dependant on the volume or
believed volume of the extravasation, this is because the body processes
natural homeostatic mechanisms for dealing with small volume toxic injuries.
Table 1 above may help practioners in assessing the volume of material
extravasated and in deciding the type of intervention which is appropriate.
Table 3: Possible Topical, Subcutaneous
Chemotherapy Extravasations.
Antidote
and
Chemotherapy agents used
with
DMSO 50 to Epirubicin,
Doxorubicin,
99%*
Daunorubicin,
Idarubicin,
Mitoxantrone, Mitomycin C,
[Topical]
Dactinomycin
Liposomal
doxorubicin (Caelyx & Myocet),
Liposomal
Daunorubicin
(DaunoXome), Amsacrine**
Dexrazoxane
Epirubicin,
Doxorubicin,
Daunorubicin, Idarubicin
Systemic
antidotes
for
Method of Use
Apply 2 hourly to the effected
area and allowed to dry
without occlusion for the
first 24hours then QDS for 7
to 14 days (21 days for
liposomal preparations).
Intravenously 1g/m2 on day 1
& 2 and 500mg/m2 on day 3
[Systemic]
at approximately 24 hour
intervals, and started within 6
hours of the extravasation.
Mustine, Treosulfan, Busulfan Instil subcutaneously to the
Cisplatin,
Carboplatin, effected area by the ‘pin
Oxaliplatin**, Arsenic**
cushion’ technique.
Sodium
Thiosulphate
(0.3%)
[Subcutaneous]
Desferrioxamine Cisplatin,
Carboplatin, 500mg in 2ml of water for
Oxaliplatin**, Arsenic**
injection,
instilled
[Subcutaneous]
subcutaneously
to
the
effected area by the ‘pin
cushion’ technique.
Hyaluronidase
Vincristine,
Vinblastine, The IMMEDIATE use of
1500iu
per Vindesine,
Vinorelbine, hyaluronidase
as
an
Paclitaxel, Docetaxel, nab “antidote” is recommended
2ml***
Paclitaxel (Abraxis)**
essentially the practioners is
[Subcutaneous]
moving straight through to
STEP 9 of the standard
pathway.
* The high the concentration available the greater and quicker it ‘solvent’ action is
believed to work.
** Untried
*** Diluted concentration after the addition of Water for Injection to the lyophilised
powder.
I. The chronic use of antidotes is only applicable to those applied topically and
should be administered in sequence with topical symptomatic measures such
as hydrocortisone cream.
J. The subcutaneous hyaluronidase opens up the intracellular space around and
throughout the affected area to allow for easier dispersal by natural body
mechanisms.
K. If the agent in question is hyper or hypo tonic to the surrounding tissues the
addition of subcutaneous fluid (0.9% sodium chloride) will minimise the
damage, furthermore if the pH of the extravasated fluid is close to the bodies
natural buffer range 5.5 to 8.5 then dilution by a factor of 10 i.e. with 10ml if
1ml is believed to have extravasated or 100ml if the extravasation is as large
as 10mls with s/c fluid will reduce the local pH by 1pH unit. The fluid should
be administered by the technique known as hypodermoclysis.
L. The area of the extravasation injury can be warmed using either a single use
‘thermal’ bandage, or a hot water bottle or microwavable ‘bean bag’ or using a
small electric blanket. The chosen heat sores should not be applied directly to
the extravasated area, but intermittently with a degree of gentle compression,
the injury protected from the heat source via some plain gaze or the source
wrapped in a pillow case or tea towel.