Makindo Medical Notes

Introduction

End-of-life care aims to provide comfort and support to patients in the final stages of life. Effective symptom management is crucial to alleviate distress and improve the quality of remaining life. This guide outlines best practices for prescribing medications to manage common symptoms such as pain, dyspnea, agitation, respiratory secretions, nausea, and convulsions in palliative care settings.

Note: All medications and dosages should be verified with current clinical guidelines and prescribing references, such as the British National Formulary (BNF). Use opioids cautiously in patients with renal impairment (eGFR <30 mL/min/1.73 m²); consider alternatives like oxycodone instead of morphine.

Principles of End-of-Life Prescribing

• Regularly assess and document symptoms and their impact on the patient's comfort and quality of life.
• Use the least invasive route of administration; subcutaneous (SC) injections are preferred when the oral route is not feasible.
• Anticipate and manage potential side effects, such as constipation from opioids, by prescribing prophylactic medications like laxatives.
• Adjust dosages based on individual patient response and symptom severity.
• Communicate effectively with the patient (if possible), family, and multidisciplinary team to ensure holistic care.

Symptom Management

The following table summarizes common symptoms at the end of life and their initial management options. Prescribing should be individualized based on patient needs, comorbidities, and renal function.

Symptom	Medication Options	Dosage (Subcutaneous unless specified)	Notes
Pain and/or Dyspnea	Morphine sulfate Oxycodone (if eGFR <30 mL/min/1.73 m²)	Morphine: 2.5-5 mg hourly PRN Oxycodone: 1.25-2.5 mg hourly PRN	Consider starting a continuous infusion if frequent dosing is required.
Agitation and Anxiety	Midazolam Haloperidol (if delirium suspected) Lorazepam (sublingual, if oral route possible)	Midazolam: 2.5-5 mg hourly PRN Haloperidol: 0.5-1 mg every 2-4 hours PRN Lorazepam: 0.5 mg sublingual PRN up to 4 times daily	Adjust dose based on sedation level and symptom control.
Respiratory Secretions	Glycopyrronium Hyoscine butylbromide Hyoscine hydrobromide	Glycopyrronium: 0.2 mg every 4 hours PRN Hyoscine butylbromide: 20 mg hourly PRN Hyoscine hydrobromide: 0.4 mg every 4 hours PRN	Anticholinergic side effects may occur; monitor for urinary retention.
Nausea and Vomiting	Haloperidol Levomepromazine Metoclopramide Cyclizine	Haloperidol: 0.5-1 mg every 4 hours PRN Levomepromazine: 2.5-6.25 mg every 6-8 hours PRN Metoclopramide: 10 mg every 6-8 hours PRN Cyclizine: 50 mg every 8 hours PRN	Choose antiemetic based on likely cause of nausea.
Convulsions	Midazolam	Midazolam: 5-10 mg stat dose, then 20-30 mg over 24 hours via continuous infusion	Continue existing antiepileptic medications if possible.

Use of Syringe Drivers

A syringe driver is a portable battery-operated device that delivers medications subcutaneously over a set period (usually 24 hours). It is used when the oral route is not viable due to nausea, vomiting, dysphagia, or reduced consciousness.

Starting a Syringe Driver

• Opioid-Naïve Patients:
  • Morphine sulfate: 10 mg over 24 hours SC
  • Midazolam: 10 mg over 24 hours SC
  • If eGFR <30 mL/min/1.73 m², use oxycodone 5 mg instead of morphine
• Patients with Severe Symptoms (e.g., severe pain, agitation, respiratory distress):
  • Morphine sulfate: 20 mg over 24 hours SC
  • Midazolam: 20 mg over 24 hours SC
  • If eGFR <30 mL/min/1.73 m², use oxycodone 10 mg instead of morphine
• Adjustments: Dosages should be titrated based on symptom control and patient response. Regularly reassess the patient and adjust the infusion rate accordingly.

Medications Commonly Used in Syringe Drivers

The following medications are commonly combined in syringe drivers. Compatibility must be checked before mixing, and the solution should be inspected regularly for precipitation or discoloration.

• Opioids: Morphine sulfate, diamorphine, oxycodone
• Benzodiazepines: Midazolam for sedation and seizure control
• Antiemetics: Haloperidol, levomepromazine, cyclizine (note compatibility issues)
• Anticholinergics: Glycopyrronium, hyoscine butylbromide, hyoscine hydrobromide
• Steroids: Dexamethasone (monitor for precipitation when mixed)

Considerations for Renal Impairment

In patients with reduced renal function (eGFR <30 mL/min/1.73 m²), certain medications require dosage adjustments or alternative choices to prevent accumulation and toxicity.

• Opioids:
  • Avoid morphine due to active metabolites that accumulate in renal impairment.
  • Use oxycodone with caution; start at lower doses.
  • Consider fentanyl or alfentanil in severe renal impairment.
• Other Medications:
  • Adjust doses of sedatives and antipsychotics as needed.
  • Monitor for increased sensitivity to medications.

Medications and Compatibility

Mixing medications in a syringe driver requires careful consideration of compatibility and stability. Incompatible combinations can lead to precipitation, reduced efficacy, or increased risk of adverse effects.

Compatible Combinations with Morphine or Diamorphine

• Morphine/Diamorphine with:
  • Midazolam
  • Haloperidol
  • Glycopyrronium
  • Hyoscine butylbromide
  • Levomepromazine (may cause slight cloudiness)
  • Metoclopramide (monitor for site reactions)

Note: Cyclizine can precipitate when mixed with certain opioids and in high concentrations. Consult compatibility charts or pharmacists when in doubt.

Monitoring and Adjustments

• Regularly assess symptom control and adjust medication dosages accordingly.
• Monitor for side effects such as sedation, respiratory depression, urinary retention, and constipation.
• Ensure that the syringe driver is functioning correctly and check the infusion site for signs of inflammation or irritation.
• Communicate any changes in the patient's condition to the healthcare team promptly.

Management of Specific Symptoms

Pain Control

Effective pain management is a cornerstone of end-of-life care. Opioids are the mainstay for moderate to severe pain.

• Starting Doses:
  • Morphine sulfate: 2.5-5 mg SC every 4 hours PRN
  • Oxycodone: 1.25-2.5 mg SC every 4 hours PRN (if renal impairment)
• Titration: Increase doses gradually based on pain assessment and patient tolerance.
• Adjuvant Analgesics: Consider adding non-opioid analgesics or adjuvant medications (e.g., anticonvulsants for neuropathic pain) as appropriate.
• Side Effects Management: Prescribe laxatives to prevent opioid-induced constipation. Monitor for nausea and sedation.

Agitation and Restlessness

Agitation may be due to pain, urinary retention, metabolic disturbances, or psychological factors.

• Midazolam: Useful for sedation and anxiety relief.
  • Starting dose: 2.5-5 mg SC hourly PRN
  • Continuous infusion: 10-30 mg over 24 hours SC
• Haloperidol: Preferred if delirium is suspected.
  • Starting dose: 0.5-1 mg SC every 2-4 hours PRN
  • Continuous infusion: 2.5-10 mg over 24 hours SC
• Levomepromazine: Alternative antipsychotic with sedative properties.
  • Starting dose: 12.5 mg SC every 6-8 hours PRN
  • Continuous infusion: 12.5-50 mg over 24 hours SC

Respiratory Secretions

Noisy respiratory secretions (the "death rattle") can be distressing for family members.

• Anticholinergic Medications:
  • Glycopyrronium: 0.2 mg SC every 4 hours PRN or 0.6-1.2 mg over 24 hours via infusion
  • Hyoscine hydrobromide: 0.4 mg SC every 4 hours PRN or 1.2-2.4 mg over 24 hours via infusion
  • Hyoscine butylbromide: 20 mg SC every 4 hours PRN or 60-120 mg over 24 hours via infusion
• Avoid overhydration, which may exacerbate secretions.
• Repositioning the patient may help reduce noise from secretions.

Nausea and Vomiting

Management depends on the underlying cause (e.g., chemical, visceral, intracranial).

• Haloperidol: Effective for opioid-induced or metabolic nausea.
  • 1-3 mg SC at night or every 12 hours
  • Continuous infusion: 1.5-5 mg over 24 hours SC
• Metoclopramide: Prokinetic agent useful for gastric stasis.
  • 10 mg SC every 6-8 hours PRN
  • Continuous infusion: 30-60 mg over 24 hours SC
• Cyclizine: Antihistamine for vestibular causes.
  • 50 mg SC every 8 hours PRN
  • Continuous infusion: 100-150 mg over 24 hours SC
• Note: Cyclizine may cause site irritation and compatibility issues when mixed.
• Levomepromazine: Broad-spectrum antiemetic.
  • 6.25-12.5 mg SC at night
  • Continuous infusion: 6.25-25 mg over 24 hours SC
• Higher doses may cause sedation.

Convulsions

Patients with a history of seizures or at risk (e.g., brain tumors, renal failure) should continue antiepileptic therapy if possible.

• Midazolam:
  • 5-10 mg SC stat dose for acute seizure
  • Continuous infusion: 20-60 mg over 24 hours SC
• Consider consulting a specialist if seizures are difficult to control.

Conclusion

Effective end-of-life care prescribing requires careful assessment, regular monitoring, and individualized treatment plans. Collaboration with palliative care specialists, pharmacists, and the multidisciplinary team enhances the quality of care provided to patients and supports their families during this critical time.

References

• British National Formulary. BNF 82. London: BMJ Group and Pharmaceutical Press; 2021.
• NICE. Care of Dying Adults in the Last Days of Life. NICE Guideline [NG31]; 2015.
• Scottish Palliative Care Guidelines. Symptom Control Medication. Available at: https://www.palliativecareguidelines.scot.nhs.uk/
• Twycross R, Wilcock A, Howard P. Palliative Care Formulary. 6th ed. Nottingham: Palliativedrugs.com Ltd; 2017.
• e-Learning for Healthcare. Palliative Care. Health Education England; 2021.