choice of drugs for use in syringe drivers - Palliative Care Resources

LIVERPOOL CARE PATHWAY FOR THE DYING PATIENT
PRINCIPLES OF MANAGEMENT
The principles are applicable to the care of patients dying from cancer and non-malignant disease.
RECOGNISE THAT DEATH IS APPROACHING
Studies have found that dying patients will manifest some or all of the following:
• Profound weakness - usually bedbound
• Drowsy or reduced cognition - semi-comatose
• Diminished intake of food and fluids - only able to take sips of fluid
• Difficulty in swallowing medication - no longer able to take tablets
TREATMENT OF SYMPTOMS
The prime aim of all treatment at this stage is the control of symptoms current and potential.
• Discontinue any medication which is not essential
• Prescribe medication necessary to control current distressing symptoms
• All patients who are dying would benefit from having subcutaneous medication prescribed
IN CASE distressing symptoms develop
• All medication needs should be reviewed every 24 hours
• If two or more doses of prn medication have been required, then consider the use of a
syringe driver for continuous subcutaneous infusion (CSCI)
The most frequently reported symptoms are:-
• Pain
• Nausea / Vomiting
• Excessive secretions / Noisy breathing
• Agitation / Restlessness
• Dyspnoea
OPIOID CHOICE AND SYRINGE DRIVERS
Morphine sulphate is the injectable opioid of choice in the majority of patients.
Alternative opioids (when morphine is not tolerated or in patients with severe renal failure e.g GFR <
30mL /min) include oxycodone or alfentanil.
Morphine sulphate and oxycodone are both compatible with all the medications that are
recommended in the following guidelines (cyclizine, haloperidol, levomepromazine, hyoscine
butylbromide, glycopyrronium, metoclopramide and midazolam).
Alfentanil is also compatible with all the above medications that are recommended, with the
exception of cyclizine.
Use either water for injection or sodium chloride 0.9 % as the diluent, unless mixing with cyclizine,
when water for injection must be used.
Although 10mL syringes are the standard size usually used in the syringe driver, if volumes are
larger it may be necessary to use a 20mL or 30mL syringe instead.
For more information on the usual doses of drugs used in a syringe driver see page 41
For guidance on converting between opioids see the back page.
Contacts for clinical advice are on page 3
For advice on compatibility contact Pharmacy Medicines Information ext 5960
The algorithms will support you in your management of the most frequently reported symptoms.
1

PAIN CONTROL
(Non renal pathway – see next page for patients with renal failure)
Strong opioid Conversion to s/c morphine over 24 hours Example
Zomorph/ MST Divide total oral morphine dose by 2 Zomorph 30mg bd = 30mg Morphine s/c in 24 hours
Fentanyl patch Standard practice is to leave fentanyl patch on
patient and change every 3 days.
Top up with s/c doses of morphine and review.
Fentanyl patch 75 microgram changed every 72 hours
is approximately equivalent to
morphine 270mg oral or 140mg s/c over 24 hours
To calculate prn s/c morphine dose to supplement
patch
a) Work out equivalent 24 hour oral morphine dose for
a given patch
b) Divide by 2 to get s/c 24 hour morphine dose
c) Divide by 6 to get s/c morphine prn dose
The prn dose can be given every 4 hours up to a
maximum of 6 prn doses in 24 hours
A syringe driver may be required if 2 or more prn doses
are used.
Subsequent breakthrough dose should be calculated
from the dose of morphine in the syringe driver and the
equivalent given by patch
2
Leave patch on and calculate initial prn dose as 1/6 th
of 140mg morphine s/c over 24 hours = 25mg
A syringe driver may be required if 2 or more doses
used in the past 24 hours.
E.g. If 2 prn doses are used (2 x 25mg) the syringe
driver would be set up with 50mg morphine s/c over 24
hour
Calculate subsequent prn morphine s/c doses
Add morphine syringe driver dose i.e 50mg s/c with
equivalence in patch i.e 140mg morphine s/c.
Total equivalent s/c morphine dose in 24 hour = 50mg
+ 140mg =190mg
New prn doses would be 1/6 th of 190mg = 32mg
(prescribe 30mg for convenience).
Consult opioid conversion chart on back page
Remember to include prn doses in your calculations

PAIN CONTROL
(Patients with severe renal failure ie GFR < 30mL/min)
Strong opioid Conversion to s/c alfentanil over 24 hours Example
MST/ Zomorph Divide total oral morphine dose by 30 Zomorph 30mg bd = 2mg alfentanil s/c over 24 hours
OxyCodone Divide total oral oxycodone by 15 OxyContin15mg bd =2mg alfentanil s/c over 24 hours
Fentanyl patch
microgram/hour
Standard practice is to leave fentanyl patch on
patient and change every 3 days.
Top up with s/c prn doses of alfentanil and review
To calculate prn s/c alfentanil dose to
supplement patch
a)Either divide fentanyl patch strength by 50 to get
prn s/c alfentanil dose ( in mg). This is an
approximation and may slightly under estimate
requirements. OR
b)1/6 th of equivalent 24 hour alfentanil s/c dose
The prn dose can be given every 2 to 4 hours up to
a maximum of 6 prn doses in 24 hours
A syringe driver may be required if 2 or more prn
doses are used.
Subsequent breakthrough dose should be
calculated from the dose of alfentanil in the syringe
driver and the equivalent given by patch.
3
Fentanyl patch 75 microgram changed every 72 hours
is approximately equivalent to 9mg alfentanil s/c over 24
hours
Leave patch on and calculate initial prn dose as
a)1/50 th patch strength = 1.5mg OR
b)1/6 th of equiv 24 hour alfentanil sc dose 9mg =1.5mg
A syringe driver may be required if 2 or more doses used
in the past 24 hours.
E.g. If 2 prn doses are used (2 x 1.5mg) the syringe driver
would be set up with 3mg alfentanil over 24 hours
Calculate subsequent prn alfentanil s/c doses
Add alfentanil syringe driver dose i.e 3mg s/c with
equivalence of alfentanil in patch i.e 9mg s/c.
Total equivalent 24 hour s/c alfentanil dose = 3mg + 9mg
=12mg
New prn dose would be 1/6 th of 12 mg = 2mg
Prn doses will need increasing as syringe driver
requirements increase
Consult opioid conversion chart on back page
Remember to include prn doses in your calculations

NAUSEA AND VOMITING
4

RESPIRATORY TRACT SECRETIONS
(Remember you cannot clear existing secretions, but you can help
stop further production)
HYOSCINE BUTYL BROMIDE (BUSCOPAN) occasionally can precipitate when mixed with
CYCLIZINE. If problems discuss with pharmacy.
GLYCOPYRRONIUM may be used as an alternative if Hyoscine Butylbromide not effective (reduced
doses in renal failure) See page 41
HYOSCINE HYDROBROMIDE is not recommended in patients with renal failure because of
excessive drowsiness or paradoxical agitation
5

AGITATION / TERMINAL RESTLESSNESS
Yes
Is agitation/ terminal
restlessness present
No
Prescribe and adminster
MIDAZOLAM
2.5 to 5mg s/c every 4 hours
prn
Prescribe
MIDAZOLAM
2.5 to 5mg s/c
every 4 hours prn
(to be administered only if the
patient develops symptoms)
Review
every 24 hours
Have more than
2 prn doses been given
in 24 hours
No
Yes
Convert to a
syringe driver
Calculate
amount of MIDAZOLAM administered
over the last 24 hours and set up a
syringe driver with this dose
and
2.5 to 5mg s/c every 4 hours prn
Continue with
MIDAZOLAM
2.5 to 5mg s/c
every 4 hours prn
Yes
Is the patient’s
agitation controlled
No
Review
every 24 hours
Continue with
current
prescription
Increase dose of
MIDAZOLAM in syringe driver to
maximum of 60mg
(30mg in renal failure) in 24 hours
and
2.5 to 5mg s/c every 4 hours prn
Maximum dose in 24 hours is 60mg
(30mg in renal failure) which includes
both prn doses and syringe driver
Seek advice if more required
If patient still agitated levomepromazine may be required see page 41 or
contact palliative care team for advice
6

DYSPNOEA (BREATHLESSNESS)
(Non renal pathway –see next page for patients with renal failure)
Yes
Is the patient
breathless
No
Treat reversible causes
appropriately and consider
non pharmacological
management such as
positioning, cool air,
reassurance
Is the patient already
taking an opioid (oral or
patch)
No
Prescribe
MORPHINE 3 to 5mg s/c every 4 hours prn
(to be administered only if the patient
develops breathlessness)
(If concurrent anxiety consider also prescribing
MIDAZOLAM 2.5mg s/c every 4 hours prn)
Yes
NB if patient sensitive to morphine use alternative –
but note lack of evidence for other opioids
Use prn doses for breathlessness even if not in pain
Convert to MORPHINE (or alternative opioid)
24 hour s/c infusion using the opioid conversion table
plus
s/c dose every 4 hours prn
If the patient is on a opioid patch
Leave the patch on and initially top up with prn morphine
or alternative opioid.
If over the next 24 hours 2 or more prn doses are
required set up a 24 hour s/c syringe driver with
appropriate opioid.
The prn dose of morphine (or alternative opioid) used
should take account of both the patch and the syringe
driver
Yes
Have more than
2 prn doses been given
in 24 hours
No
Continue with
MORPHINE
3 to 5mg s/c every 4 hours prn
+/- MIDAZOLAM
If concurrent anxiety
Consider also prescribing MIDAZOLAM 2.5mg s/c every 4
hours prn.
If more than 2 prn doses required in
24 hours put total dose given in 24 hours into syringe
driver
Maximum MIDAZOLAM dose 60mg in 24 hours
To calculate the prn dose of morphine or
alternative opioid
Prescribe 1/6th of the 24 hour dose in the syringe
driver
e.g 20mg morphine s/c via driver over 24 hours
will require
3 to 5mg s/c morphine every 4 hourly prn
7

DYSPNOEA
(Patients with severe renal failure ie GFR < 30mL/min)
Yes
Is the patient
breathless
No
Treat reversible causes
appropriately and consider
non pharmacological
management such as
positioning, cool air,
reassurance
Is the patient already
taking an opioid (oral or
patch)
No
Prescribe
ALFENTANIL 250 micrograms s/c every 2 to
4 hours prn
(up to a maximum of 6 prn doses in 24 hours)
(to be administered only if the patient
develops breathlessness)
(If concurrent anxiety consider also
prescribing MIDAZOLAM 2.5mg s/c every 4
hours prn)
Yes
Use prn doses for breathlessness even if not in pain
If patient is already taking and tolerating oral
OXYCODONE convert to 24 hour s/c syringe driver plus
s/c dose every 4 hours prn
Yes
Convert to
syringe driver
Have more than
2 prn doses been given
in 24 hours
OTHERWISE
Convert to ALFENTANIL
24 hour s/c infusion using the opioid conversion table
plus
s/c dose every 2 to 4 hours prn (up to a maximum of 6
prn doses in 24 hours)
If the patient is on a opioid patch
Leave the patch on and initially top up with prn alfentanil.
If over the next 24 hours 2 or more prn doses are
required set up a 24 hour s/c syringe driver with alfentanil
The prn dose of alfentanil used should take account of
both the patch and the syringe driver
If concurrent anxiety
Consider also prescribing MIDAZOLAM 2.5mg
s/c every 4 hours prn.
If more than 2 prn doses required in
24 hours put total dose given in 24 hours into syringe
driver
Maximum MIDAZOLAM dose 30mg in 24 hours
No
Continue with
ALFENTANIL 250 micrograms s/c
every 2 to 4 hours prn
(up to a maximum of 6 prn doses in 24 hours)
+/- MIDAZOLAM
To calculate the prn dose of alfentanil
Prescribe 1/6th of the 24 hour dose
in the syringe driver
e.g 3mg alfentanil s/c via syringe driver over
24 hours will require
500 micrograms s/c alfentanil
every 2 to 4 hours prn
(up to a maximum of 6 prn doses in 24 hours)
If symptoms continue contact the specialist palliative care
team
Note : Morphine would normally be used for breathlessness as this is the opioid which has the best
evidence base for treatment of breathlessness. In renal impairment however morphine accumulates and
alfentanil or oxycodone is preferred for this reason.
8

CHOICE OF DRUGS FOR USE IN SYRINGE DRIVERS
(USUAL DOSE RANGES QUOTED)
If your patient has renal failure look at the cautions in red
Drug Use Stat Dose
S/C
Anti emetic
CYCLIZINE
50mg in 1ml
HALOPERIDOL
5mg in 1ml
METOCLOPRAMIDE
10mg in 2ml
LEVOMEPROMAZINE
25mg in 1ml
Anti agitation
MIDAZOLAM
10mg in 2ml
LEVOMEPROMAZINE
25mg in 1ml
Anti secretory
HYOSCINE
BUTYLBROMIDE
20mg in 1ml
GLYCOPYRRONIUM
Centrally acting on vomiting
centre.
Good for nausea associated with
bowel obstruction or increased
intracranial pressure
Dilute with water
Note Dose reduction may be
necessary in renal, cardiac or
liver failure e.g. 25mg
Good for chemically induced
nausea
Antiemetic action
1. Prokinetic (accelerates GI
transit)
2. Centrally acting on chemoreceptor
trigger zone (CTZ),
blocking transmission to
vomiting centre
Broad spectrum antiemetic, works
on CTZ and vomiting centre (at
lower doses)
Dilute with sodium chloride 0.9%
when used alone
Sedative/anxiolytic (terminal
agitation). Also anticonvulsant
and muscle relaxant
Antipsychotic used for terminal
agitation (2 nd line to midazolam)
Antisecretory - useful in reducing
respiratory tract secretions.
Has antispasmodic properties
May precipitate when mixed with
cyclizine or haloperidol
Less sedating than HYOSCINE
HYDROBROMIDE as does not
cross the blood brain barrier
Antisecretory - useful in reducing
respiratory tract secretions
Also has antispasmodic
properties
9
50mg
(25mg in patients with
renal/heart/ liver
failure.)
Do not use if patient
has two or more of
above risk factors
1.5mg
May need lower dose in
elderly/renal failure
0.5mg=500microgram
10mg
(5 to 10mg)
24 hours S/C
dose in
syringe driver
(SD)
100 to 150mg
(75 to 100mg in
renal/heart/liver
failure)
Usual maxm
dose in
24 hours
(PRN + SD)
150mg
(75 to 100mg in
renal/heart/liver
failure)
1.5 to 3mg 5mg
30 to 60mg
(30mg in
renal failure)
120mg
(30mg in
renal failure)
5 to 6.25mg 5 to 25mg 25mg
2.5 to 5mg
Always start low
For major bleeds use
10mg
6.25 to 12.5mg
Start with lower dose &
titrate
5 to 60mg
(30mg in renal
failure)
Start with lower
dose & titrate
6.25 to 50mg
Seek help with
higher doses
60mg
(30mg in renal
failure)
200mg
(25mg to 50mg
in renal failure)
20mg 40 to 120mg 240mg
200mcg
(100microgram)
400mcg to
1200microgram
(1.2mg)
(200 to
600microgram)
1200
micrograms
(1.2mg)
(600microgram
in renal failure)