Refer to 16.2 Pain Control in Palliative Care for oral and subcutaneous opioids

Morphine sulfate is now the first line opioid for SC injection instead of diamorphine.

If a patient has a fentanyl patch, then special considerations are required – see the section for Transdermal Opioids under section 16.2 Pain Control in Palliative Care

Refer to 16.9 Breathlessness in palliative care

Present

1. Single dose
   
   1. Levomepromazine 6.25mg SC and 6 hourly when required, or
   2. Haloperidol 1mg - 2.5mg SC and 8 hourly when required, or
   3. Cyclizine 50mg SC and 8 hourly when required
2. If 2 or more doses given in 24 hours/recurrent symptoms, start SC syringe driver 24 hourly, depending on what the patient has been having orally:
   
   1. Metoclopramide 30mg, or
   2. Cyclizine 100mg - 150mg (use water for injection)
   3. And/or Haloperidol 3mg - 5mg
3. If 2 or more doses in 24 hours / recurrent symptoms, stop above and give:
   
   1. Levomepromazine 6.25mg - 12.5mg SC 24 hourly in syringe driver

It is sometimes necessary to miss step 2 and go straight to step 3.

Absent

Prescribe:

• Levomepromazine 6.25mg SC 6 hourly when required, or
• Haloperidol 1mg - 2.5mg SC 8 hourly when required, or
• Cyclizine 50mg SC 8 hourly when required

If symptoms persist contact the local specialist palliative care team

Present

1. Single dose
   
   1. Midazolam 2.5mg - 10mg SC every 30 minutes until patient settles.
   2. If more than 40mg given contact the local specialist palliative care team for advice
   3. Consider adding levomepromazine 12.5mg - 25mg SC or haloperidol 5mg SC
2. If 2 or more doses in 24 hours or recurrent symptoms, consider using a syringe driver SC 24 hourly:
   
   1. Midazolam 20mg - 30mg. In exceptional circumstances, doses of up to 100mg of midazolam may be required
   2. Consider adding levomepromazine 12.5mg - 50mg or haloperidol 10mg - 20mg

Absent

• Prescribe: Midazolam 2.5mg – 5mg SC when required

For acute confusional states, consider olanzapine where the patient is able to swallow or haloperidol s/c 1mg – 3mg where the patient is unable to swallow.

Consider short acting and least restrictive options to control distress

Consider and exclude or treat urinary retention, uncontrolled pain

If symptoms persist contact the local specialist palliative care team

• Re-positioning of patient often helps
• Reassurance of family is often helpful, e.g. "the rattly noise is like a floppy snore because their muscles are so weak"
• If unconscious, patient unaware and not distressed by this situation
• Drug treatment may be ineffective

Present

Single dose hyoscine hydrobromide 400 microgram SC and 4 hourly when required.

If successful after 1 or 2 doses start hyoscine hydrobromide 1.2mg SC 24 hourly in syringe driver.

If further breakthroughs needed - increase to hyoscine hydrobromide 2.4mg SC 24 hourly in syringe driver

Absent

Prescribe hyoscine hydrobromide 400microgram SC 4 hourly when required

If symptoms persist contact the local specialist palliative care team

Sometimes, patients who are dying have renal impairment as part of multiple organ dysfunction during the dying process. A low eGFR can result in problems with retaining opioids and their by-products. This can cause opioid toxicity causing agitation and distress.

They may need either a lower dose of standard medications prescribed or “renal friendly" drugs.

Signs of opioid toxicity to look for are:

• “Plucking" of the fingers in the air
• Myoclonic jerks
• Hallucinations
• Drowsiness with a slow respiratory rate

These can be difficult signs to spot and sometimes those who are in the final few hours of life exhibit these signs in a phase of the dying process sometimes known as “terminal agitation".

If patients are known to the Renal Team with Chronic Kidney Disease stage 4 or 5 and an eGFR less than 30, then it is likely that toxic levels of opioids and by-products may build up unless “renal friendly" drugs are used.

If a patient has opted for conservative treatment or is withdrawing from Haemo- or Peritoneal Dialysis, then SC fentanyl or alfentanil should be used in preference to other injectable opioids.

Talk to senior team members, the renal team or the specialist palliative care team to get advice about when it might be appropriate to use “renal friendly" drugs.

Have an extremely low threshold for contacting the renal team or the specialist palliative care team for patients with eGFR less than 30.

Levetiracetam concentrate for intravenous infusion may be prescribed on the recommendation of a specialist when it is to be administered as a continuous subcutaneous infusion in the circumstances described below.

Supporting guidance for levetiracetam continuous subcutaneous infusion in the community setting has been developed by consultants in palliative medicine working across Devon. The guidance is hosted on the Rowcroft Hospice website.

Levetiracetam (24 hour continuous subcutaneous infusion)

• For patients with an ongoing seizure risk who were receiving oral levetiracetam and for whom oral administration is no longer possible:
  • on the recommendation of a palliative care specialist and
  • when midazolam is inappropriate or not desired due to sedative effects
• Off label use - levetiracetam concentrate for intravenous infusion is not licensed for use in patients without epilepsy or for subcutaneous administration. For information on its use as a continuous subcutaneous infusion in palliative care, see the Palliative Care Formulary version 7 (PCF7) and the Scottish Palliative Care Guidelines.
• Levetiracetam concentrate for intravenous infusion 500mg/5mls is to be diluted and administered as a 24 hour continuous subcutaneous infusion (see below).
• For a patient currently receiving oral levetiracetam the ratio for conversion from oral to subcutaneous use is 1:1.
• Renal impairment: dose adjustment is required, seek guidance from specialist palliative care team (for further information see the Palliative Care Formulary version 7 (PCF7) and the Scottish Palliative Care Guidelines).
• There is no need to reduce the dose in hepatic impairment unless associated with renal impairment.

Notes for prescriber

• Prescribe by brand to aid identification when different presentations are available (Desitrend ampoules or Keppra vials – see section 4.8.1 Control of the epilepsies).
• Each levetiracetam ampoule or vial contains 500mg levetiracetam (pack of 10). Order two packs for the first prescription if total daily oral dose is at the higher end of the dose range.
• Diluent: Use water for injection or sodium chloride 0.9% as a diluent. Should be diluted as much as is practical to avoid site irritation.
• Compatibility: refer to the Supporting guidance for levetiracetam continuous subcutaneous infusion hosted on the Rowcroft Hospice website.
• As with all palliative care medicines administered by syringe pump, responsibility for identifying when further supplies of medicines are needed lies with the nursing teams administering the medicines. Advice on planning for a supply of levetiracetam from community pharmacies is included in the Supporting guidance for levetiracetam continuous subcutaneous infusion. Levetiracetam concentrated solution for intravenous infusion is:
  • not routinely held in stock by community pharmacies, and
  • not included on the Specialist Medicines List, and therefore is not routinely stocked by specialist pharmacies
• Advanced care planning:
  • Most patients will have either primary or secondary brain tumours, and advanced disease with a prognosis of a short number of weeks, or less.
  • The community palliative care teams can assist by identifying patients known to the teams who are receiving oral levetiracetam to consider whether levetiracetam in a syringe pump is likely to be required.
  • Early warning that the patient may be approaching the point where oral administration is not possible would be helpful to ensure timely availability of levetiracetam for infusion from the community pharmacy. Anticipatory prescribing of injectable levetiracetam is not recommended.
  • The specialist palliative care teams are available to discuss patients not known to their teams who may be suitable for levetiracetam administered in a syringe pump. See section 16.1.
• Support from the palliative care teams: The palliative care consultants are available to provide specialist telephone advice, support on prescribing and help with decision making about levetiracetam prescribing 24/7 (see here section 16.1)

Note for community pharmacies:

• Desitrend ampoules (Desitin Ltd) are available to order through Alliance Healthcare and AAH
• Keppra vials (UCB Pharma Ltd) are available to order through Alliance Healthcare.

Supporting guidance

Supporting guidance for levetiracetam continuous subcutaneous infusion in the community setting has been developed by consultants in palliative medicine working across Devon. The guidance is hosted on the Rowcroft hospice website.

In addition to the information provided above, the guidance covers:

• Dosing in renal impairment
• Compatibility with other medicines administered using a syringe pump
• Volumes and diluent
• Planning for a supply of levetiracetam concentrate for infusion from community pharmacy
• Side effects
• Action to take if levetiracetam is not available or in the event of seizures
• Palliative care team contact details