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318 Chapter 21

drowsiness, in this context these medications are used to

help manage agitation and distress towards the end-of-life

when non-pharmacological methods have not been

successful.

For certain drugs, with long half-lives, for example,

levomepromazine, dexamethasone, it may be more prac-

tical to administer via bolus injection once or twice daily.

Certain characteristics can also make drugs less suitable

for continuous infusion, for example, dexamethasone has

the potential to cause psychological stimulation, meaning

that infusion overnight may disturb sleep.

If following the commencement of an infusion the drug

dosages need to be altered, a new syringe should be set up

rather than altering the rate of the current infusion.

Alteration of the rate will deliver all the drugs at an

increased or decreased speed risking poor symptom

management for the patient. Alteration of infusion rate

will also affect the time of next refilling of the syringe, risk-

ing a period with no infused medication if the supply runs

out before the next district or community nursing visit.

Compatibility and Stability of

Medications used in Syringe Pumps

Combination of drugs in a single syringe for infusion is

common practice within palliative care as it allows for

multiple symptoms to be treated while reducing the need

for multiple infusion devices and cannula sites, promoting

patient acceptance and comfort.

Under the UK Medicines Act (1968) mixing of drugs in

this way, whereby one drug is not a vehicle of administration

for the other, as detailed in the summary of product char-

acteristics, creates an unlicensed medicine. This legislation

was amended following public consultation (MLX356)

when the MHRA along with the Commission on Human

Medicines recommended that changes should be made to

the original legislation. These changes apply to palliative

care and other clinical areas where mixing of medications

is accepted as standard practice; the changes allow pre-

scribers to mix medicines and prescribe medications for

mixing by other registered healthcare professionals [43].

When prescribing medicines intended to be mixed, the

prescriber should:

•

provide written instructions on how to do so

•

must satisfy themselves that the person mixing and

administering the medications is competent to undertake

the task safely and effectively

•

exercise due diligence to ensure compatibility

information is checked using reputable information

sources when recommending combinations of medica-

tions for subcutaneous infusion

• select a suitable diluent for the infusion

The responsibility for the potential consequences of pre-

scribing medications beyond their marketing authorisa-

tion remains with the prescriber.

Consideration of the compatibility of drugs is vital to

ensure efficacy of therapy. Interactions between drugs can

be difficult to predict and may produce different effects,

including a reduction in stability resulting in precipitation

or crystallisation of the drug solution. This may cause the

infusion cannula to become blocked, the injection site to

become inflamed, and the treatment to be ineffective.

Many drug and dosage combinations have been used in

syringe pumps. Access to compatibility databases such as

on palliativedrugs.com has allowed for nationwide

information sharing on drug combinations that may be

successfully implemented for symptom management in

palliative patients.

In the UK, drugs are usually diluted with water for

injection unless there is a specific requirement to use

sodium chloride. In particular, 0.9% saline should not be

used to dilute cyclizine or higher concentrations of dia-

morphine (≥40 mg/ml) as there is a high risk of precipita-

tion. The number of drugs combined in a single syringe

should be kept to a minimum; advice should be sought

from specialist palliative care professionals or medicines

information pharmacists when using unusual drugs or

combinations via syringe pump.

Most drugs used in syringe pumps are water soluble and

can therefore be mixed. However, some drugs, for example,

phenobarbital (made up in propylene glycol), are immis-

cible with aqueous solutions and should not be used in the

same syringe as other drugs. Where situations arise that

drug compatibility issues or volume restrictions limit the

Information Resources: Drug

Compatibility in Palliative Care

• Wilcock A, Howard P, and Charlesworth S. The

Palliative Care Formulary (7th Ed.) London:

Pharmaceutical Press, 2020.

• Dickman A and Schneider J. The Syringe Pump:

Continuous Subcutaneous Infusions in Palliative Care

(4th Ed.) Oxford: Oxford University Press, 2016.

• www.palliativedrugs.com

• www.pallmed.info

• www.sign.ac.uk

• www.medicinescomplete.com (access to electronic

version of the PCF – subscription required).

https://t.me/med1917

Medicines Management in Palliative Care Including Syringe Pumps 319

ability to mix several drugs in a single syringe; it is possible

to use multiple infusion devices.

The major factor leading to incompatibility is the

relative concentration of each drug. Other factors include

pH, storage conditions, temperature, and ionic strength.

Many salts in aqueous solution undergo degradation.

Higher concentrations may lead to lower efficacy due to

instability or precipitation of drugs. Correct storage tem-

peratures should be observed for all drugs during the

administration of the infusion. Where high concentrations

of drugs are being infused, change in temperature (partic-

ularly cold) can reduce solubility and therefore induce pre-

cipitation of the drugs within the syringe. Exposure to high

temperatures may also cause incompatibility reactions to

occur. The syringe contents should also be protected from

direct sunlight by placing in an opaque pouch, holster, or

pocket to prevent photodegradation of the contents of the

syringe. Physical examination of the contents, although a

guide to compatibility, does not guarantee absence of

chemical reaction [44–56].

If the contents of the syringe become cloudy or discol-

oured before or during infusion, the syringe should be dis-

carded immediately. Should incompatibility problems

persist, and alternative drugs or routes are not available,

then a second syringe pump may be required to infuse

drugs separately. Alternatively, the use of bolus injections

may be considered if the drug has a longer duration of

action, provided that the patient’s skin condition will make

bolus injections tolerable.

Site of the Infusion

An appropriate choice of infusion site will help to mini-

mise site problems. Changing the infusion site may be

necessary if it is painful or appears to be inflamed or

swollen. The frequency of this will vary between patients

and depend on the combination of drugs used. The

extension set and needle should be changed at each resit-

ing [57]. Should there be persistent problems with irrita-

tion at the injection site, consider the following options:

•

Reducing the concentration of drugs (i.e. larger volume).

•

Changing the drug or considering an alternative route.

•

Mixing drugs with 0.9% saline (if compatible).

•

Using a plastic (Teflon or Vialon) cannula.

•

Applying hydrocortisone 1% cream to the skin around the

needle entry site and covering it with an occlusive dressing.

•

Adding dexamethasone 0.5–1 mg to the infusion (if

compatible). Dexamethasone should not be routinely

added to infusion solutions unless there is a specific

problem with infusion sites [58] and palliative care teams

should be involved with the decision-making.

Figure 3 Acceptable Sites for Subcutaneous Infusion.

https://t.me/med1917

320 Chapter 21

Choice of Site for the Infusion Cannula

Suitable sites for placement of the butterfly needle include:

•

upper chest

•

outer upper arm

•

anterior abdomen

•

thighs

•

area over the scapula may be used in confused or disori-

entated patients

Avoid:

•

deltoid area in bedbound patients who require regular

turning

•

sites over bony prominences in cachectic patients

•

broken skin

•

areas of inflammation

•

recently irradiated areas

•

tumour sites

•

oedematous/lymphaedematous areas.

The exact placement may be influenced by the patient’s

preference, by the disease process and by common sense.

Management of Subcutaneous Infusions

Dedicated syringe pump monitoring charts should be used

to ensure that the drug mixture is monitored throughout

the infusion. It is essential that the following checks are

made regularly:

• Drug and doses correct.

•

Signs of irritation or inflammation at the injection site.

•

Any evidence of leakage at the various connections.

•

The pump is working (light flashing/intermittent motor

noise).

• The set rate is correct and the corresponding amount of

fluid infused.

• Any signs of crystallisation or precipitation (cloudiness).

•

The tubing is not kinked.

The Gosport Report and Its Implications

for Palliative Care

In 2018 the Gosport Independent Panel published a report

following an investigation into the failings of care at

Gosport War Memorial Hospital between 1988 and 2000.

The implications of this report have far-reaching conse-

quences for modern-day palliative care and highlight the

importance of ensuring appropriate governance and safety

practices are implemented by all healthcare professionals

working with high risk medications including opioids.

The panel reported the following outcomes and prac-

tices of concern following their review [59, 60]:

• at least 450 patients are likely to have died after admini-

stration of inappropriate doses of opioid medications;

•

opioids appear to have been initiated without appro-

priate clinical indication and documentation as to the

rationale behind treatment;

•

large dose ranges for medications were prescribed,

allowing nursing staff with little training or knowledge in

palliative care to initiate doses of opioids and sedatives

with limited support from medical staff;

• patients were often administered combinations of med-

ications via syringe pump at exceptionally high doses; the

administration of these drugs, doses and combinations

was directly linked to patient fatalities;

• once patients were started on a syringe pump, they were

not reviewed clinically by a medical professional and doses

were escalated regardless of patient response;

•

the routine practice of prescribing excessively high

doses of opioids without justifiable medical cause went

unchallenged by pharmacists and consultants;

•

none of this practice was patient-centred; the approach

was consistent across all patients admitted regardless of

clinical condition(s) and symptom need; because it suited

the service that was available;

• concerns were raised by families and by some nursing

staff at the hospital, but these went unaddressed by the

hospital management, local police force, and the crown

prosecution service, despite multiple investigations into

the practices at the hospital.

The report highlighted that the indiscriminate use of med-

ications via syringe pump was directly contributable to

patient fatalities at the hospital; this prompted review

within specialist palliative care to ensure the safety of local

prescribing practices when administering drugs via con-

tinuous subcutaneous infusion.

The media reports of the events also raised concerns in

patients and their families who were receiving specialist

palliative care interventions at the time of the reports.

Extra reassurances and communication skills were

required during this period.

Since the events at Gosport War Memorial Hospital, and

prior to the release of the report, person-centred pharmacy

practice in hospital, hospice, and primary-care settings has

significantly changed. Pharmacists have become key mem-

bers of multi-disciplinary teams and are better placed to

challenge inappropriate prescribing practice. Medication

governance and assurance processes for the safe use of

opioid medications have also strengthened since the events

that occurred at Gosport [59–61].

Following the Shipman Inquiry in 2007 all organisations

are now legally required to appoint a Controlled Drugs

Accountable Officer (CDAO), whose role it is to manage

the safe and secure handling of controlled drugs within the

organisation. Controlled Drugs Local Intelligence Network

(CDLIN)s have also been established to support sharing of

https://t.me/med1917

Medicines Management in Palliative Care Including Syringe Pumps 321

information and areas of good practice. Implementation of

electronic prescribing systems also supports with data col-

lection and can analyse unusual patterns and trends in pre-

scribing in ways which were not available during the time

of the events at Gosport.

The practice of anticipatory prescribing of syringe

pumps is now discouraged by the Association of Supportive

and Palliative Care Pharmacists as the risks of this practice

are thought to outweigh the benefits. The practice of range

prescribing of medications for administration via syringe

pump in generalist settings is also challenged.

It is important to constantly review and audit practices,

whether as a healthcare professional or as an organisa-

tion, to ensure processes and management of patients

with palliative care needs is appropriate, patient-centred,

and safe.

Steroids in Palliative Care

Corticosteroids have been shown to be effective for a

variety of uses in the palliative care setting. The most

commonly used systemic corticosteroid in palliative care

is dexamethasone. Research has shown that as many as

50% of patients with advanced disease may be prescribed

systemic corticosteroids during their illness [62].

Common indications for steroid treatment in palliative

care include:

• Raised intracranial pressure

•

Anorexia

•

Nausea and vomiting

•

GI obstruction

•

Liver capsular pain

•

Raised SVCO

• Spinal cord compression

All patients prescribed corticosteroids should be given

treatment for the shortest time using the lowest effective

dose to limit the risk of inducing adrenal insufficiency

[63]. Ongoing need for corticosteroids should be

reviewed on a regular basis. When administering corti-

costeroids regularly they should be given once daily in

the morning, or twice daily with the last dose before 2

p.m. as this reduces suppression of the hypopituitary-

adrenal axis and may prevent corticosteroid-induced

insomnia.

Dexamethasone has a higher glucocorticoid activity and

insignificant mineralocorticoid effect compared to other

corticosteroids [6] and is the best choice for clinical sce-

narios where high-dose anti-inflammatory treatment is

required. Note that 2 mg oral dexamethasone is approxi-

mately equivalent to 15 mg oral prednisolone. It also has a

longer duration of action which means doses are no more

than once or twice a day. Alongside the potency which can

mean fewer tablets, it helps aid medication compliance

with administration.

A proton pump inhibitor (or H2-antagonist if available)

should be co-prescribed with corticosteroids for all patients

taking NSAIDS or those with two or more of the following

risk factors [64]:

•

Advanced malignancy

•

Previous history of peptic ulcer disease.

•

Starting dose of corticosteroids is equivalent to or

greater than 8 mg dexamethasone.

Gastro-protection should also be considered for patients

taking other drugs which increase the risk GI irritation and

bleeding including: SSRIs, aspirin, anticoagulants, and

bisphosphonates.

Side effects of corticosteroids include candida infection,

weight gain, bruising, thinning of the skin, diabetes

mellitus, proximal myopathy, and cushingoid features.

Hyperglycaemia is a recognised side effect of corticoste-

roid therapy, in both diabetic and nondiabetic patients. It is

therefore important to monitor glucose levels in all patients

receiving regular corticosteroid therapy.

Corticosteroids should be discontinued once symptoms

have resolved, or reduced to the lowest effective dose

required. The Committee on Safety of Medicines (CSM)

has recommended that systemic corticosteroids should be

gradually withdrawn in patients who have received

treatment for longer than three weeks.

For patients struggling to take tablets there are two

options – licensed oral liquids are available (N.B.: different

strengths are available therefore check carefully the

strength a patient tells you due to risk of errors) or the tab-

lets can be dissolved in water (unlicensed use).

For patients unable to take oral dexamethasone, doses of

less than 8 mg may be administered via a bolus subcuta-

neous injection. If a greater dose is required, dexametha-

sone can be given twice daily subcutaneously (morning

and lunchtime).

Dexamethasone injection is available as 3.3 mg/ml (1

and 2 ml amps) and 3.8 mg/ml (1 ml amps). To convert

between PO and SC routes, both 3.3 mg and 3.8 mg dexa-

methasone base of the injectable formulations can be con-

sidered approximately equivalent to dexamethasone base 4

mg PO. This is to avoid wastage of volumes and complexity

of drug calculations in preparing the dose [6].

https://t.me/med1917

322 Chapter 21

For patients in the dying phase of their illness where

they may be moribund and no longer able to take medica-

tion, it is generally acceptable to discontinue corticoste-

roids abruptly [6, 65, 66], maintenance doses may be

required to prevent withdrawal syndrome and/or where

their clinical condition/symptom control indicates steroids

to continue, for example, brain tumour and brain metas-

tases which may be causing seizures and headaches.

Monitoring Required with

Corticosteroids

• For courses over seven days, monitor blood glucose reg-

ularly during treatment (e.g. every 1–2 weeks), particularly

in patients at risk of diabetes [6].

•

Monitor for symptoms which might indicate hypergly-

caemia, for example, increased thirst, increased frequency

of micturition.

•

Steroid-induced diabetes will require medication

management alongside the continued use of the steroids,

remembering that as the steroids are weaned down/with-

drawn, so too will the diabetes medication need to be adjusted.

Diabetes UK have produced guidance to support [67].

Controlled Drugs

Controlled drugs (CDs) in the UK are subject to the

requirements of the Misuse of Drugs Regulations 2001.

The legislation categorises these drugs into five schedules

[24, 68].

Prescriptions written by non-medical prescribers can be

prescribed on the green FP10SS or purple FP10PN/FP10SP

prescriptions forms [69].

The legal requirements for prescriptions for controlled

drugs in schedules 2 and 3 to be valid are outlined in

Figure4. It is an offence for a prescriber to issue an incom-

plete prescription and it is illegal for a pharmacist to

dispense a CD unless all the information required by law

is given on the prescription.

Figure 4 CD Requirements.

Table 2 Categories of Controlled drugs list - GOV.UK (www.gov.uk)

Schedule 1 LSD and ecstasy-type substances – have

virtually no therapeutic use

Schedule 2 Principal opioids and major stimulants Medical and dental prescribers are allowed

prescribe all CDs in schedules 2–5 for the

purpose of treating organic disease.

Nurse and pharmacist independent prescribers

can prescribe, administer, and give directions for

the administration of Schedule 2–5 CDs for the

purpose of treating organic disease or injury since

2012.

Schedule 3 Most barbiturates plus buprenorphine,

midazolam, tramadol, and temazepam.

Gabapentin and pregabalin since 2019 due

to concerns around increasing abuse of

these medications

Schedule 4 Mainly benzodiazepines

Schedule 5 Low dose and dilute preparations of some

of the schedule 2 drugs e.g. morphine

sulfate oral solution 10 mg/5 ml

https://t.me/med1917

Medicines Management in Palliative Care Including Syringe Pumps 323

For CDs in schedules 2 and 3 prescribers must specify

the quantity of medication they want dispensed in both

words and figures, the RPS advises that it is best practice

to prescribe in terms of dosage units [24]. Failure to

comply with the regulations will result in inconvenience to

the patient and delay in supplying the necessary

medicines.

Prescriptions written for CDs in schedules 2–4 are valid

for 28 day after the date on the prescription, it is consid-

ered good practice to supply only an appropriate amount

for the needs of the patient and if more than 30 days’ supply

is given, then a note to justify the reason should be included

in the patient records [24].

Examples of completed CD prescriptions are shown in

Figures 5 and 6.

Taking CDs Abroad

If a patient travelling abroad requires more than three

calendar months’ supply of CD, the licencing law requires

the patient to seek a licence from the Home Office. The

licence however has no legal status outside the United

Kingdom and does not ensure safe passage through the

customs of the country of destination. The patient must

contact the Embassy or High Commission in the United

Kingdom to clarify the requirements for taking CDs

through the customs of the destination country or coun-

tries [24].

Examples of Directions that are not

legally acceptable for CD prescriptions

• As directed

• When required

• PRN

• As per chart

• Titration dose

Examples of Directions that are legally

acceptable for CD prescriptions (NB:

legally acceptable does not automatically

indicate clinical appropriateness)

• One capsule (10 mg) TWICE a DAY

• 5 mg (2.5 ml) when required maximum every FOUR hours

• 10 mg subcut prn for pain every TWO hours

Figure 5 Example of completed FP10 for oral controlled drugs.

Figure 6 Example of completed FP10 for injectable controlled

drugs.

https://t.me/med1917

324 Chapter 21

Unwanted Medicines or Disposal of CDs

after a Death at Home

A patient or their representative may return unwanted

medicines, to a community pharmacist for destruction.

Because CDs are the property of the patient they should,

where possible, be returned for destruction by the patient

or the patient’s representative, unless there are concerns

that leaving these medications in the patients’ home after

their death creates a risk of misappropriation of these

medications for example known history of substance

abuse [24, 70].

The Role of Pharmacy in Future

Palliative Care

The pharmacy team are essential to palliative care

teams in hospital, hospice, and community services.

Their role has advanced from that of medicines

management to include clinical advice and treatment

management alongside information provision to

empower patients.

Supporting patients at their preferred place of care,

often home, means that services must adapt to this need,

demonstrated with the recent COVID-19 pandemic.

The role of the pharmacist is not only in the strategic

side of co-ordinating services to help access medicines

or providing support to generalist teams with complex

specialist medicines, but has now advanced into consul-

tant roles with pharmacists managing their own case-

loads of patients either as in-patients, outpatient clinics,

or home visits.

Research in palliative care has also developed over the

years and now with interest not only in assessing the

impact of services but also in new therapies, there is an

opportunity for pharmacists to be involved from a

quantitative and qualitative perspective.

Initiatives to support access to medicines at home espe-

cially around carer administration of symptom control

medicines (e.g. CARiAD study [71]) provides opportu-

nities for pharmacists and pharmacy technicians to

support and educate those involved.

Strategic input into process mapping of patient jour-

neys, commissioning services and national projects is key

to keeping the pharmacist at the frontline of innovation

alongside their healthcare colleagues.

Key Learnings from the Chapter

• Medicines Management and Medicines Optimisation

involve healthcare professionals and patients/carers/

families.

•

The pharmacy team play a key role in specialist pallia-

tive care service delivery.

•

Anticipatory planning is essential and appropriate pre-

scribing and availability of symptom control medicines can

reduce distress or inappropriate admissions.

•

Controlled Drugs have multiple legal requirements and

their risk of diversion is high – consideration needs to be

given to this while not denying patients access to essential

medicines.

• Staff involved need to be competent and trained in the

medicines they are using within their practice – unfamil-

iarity can lead to errors and patient harm. Local guidance

and key resources need to be available. “Off-label” pre-

scribing and evidence base needs to be clear.

•

Syringe pumps/CSCIs remain the mainstay of delivering

consistent symptom control.

• It is imperative to keep communication channels open

when patients are considering using CBD/CAMs and to

ask them to keep HCPs informed if they are using it.

•

Wherever possible, deprescribing should be performed

as a partnership between the patient (and carer) and the

prescriber.

Acknowledgements

This chapter has been updated from the previous edition

written by Dr Christine Hirsch and Dr Maria McKenna.

Some content of the original chapter remains with

permission.

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