INTRODUCTION

Good symptom control remains the central goal of palliative care in patients with incurable illness. In some patients as they approach the end of life, physical, psycho-social and existential/spiritual problems may not be adequately controlled despite adequate titration of medications in combination with non-pharmacological measures. In such situations sedation may need to be considered as a therapeutic intervention to relieve distress and suffering.

Therapeutic palliative sedation is defined as monitored continued or intermittent administration of medications intended to induce a state of decreased or absent awareness (unconsciousness) to relieve the burden of otherwise intractable suffering refractory to other therapies or interventions.

The common situations requiring therapeutic palliative sedation are:

• Refractory physical symptoms
• Pain
• Breathlessness
• Vomiting
• Bleeding
• Fatigue
• Psychological
• Depression
• Anxiety
• Delirium
• Existential distress
• Feeling of hopelessness/helplessness/worthlessness/meaninglessness/dependency and isolation
• Fear or panic of impending death
• Spiritual issues

ASSESSMENT

• Assess the physical symptoms psycho-social and existential/spiritual issues and the adequacy of the therapeutic interventions to manage the same
• Assess the mental capacity of the patient to make his/her own decisions
• Assess for alcohol, benzodiazepine and nicotine withdrawal

RECOMMENDATION

• Therapeutic palliative sedation should be considered at the end of life, only after all other available treatment options have been exhausted
• Therapeutic palliative sedation should be used  with the intent of relieving distress and suffering
• Continue to administer medications such as opioids, psychotropic, anti-secretory and anti-emetics for adequate control of symptoms
• At least one other palliative care physician should be consulted by the treating physician to agree before considering therapeutic palliative sedation
• Patient, family and health care providers should agree before initiating therapeutic palliative sedation
• Minimum quantity of medications should be used to achieve adequate relief of suffering
• Midazolam is the most commonly used medication for therapeutic palliative sedation
• Use Richmond Agitation-Sedation Scale (RASS) as a guide for increasing or decreasing sedation – https://www.mdcalc.com/richmond-agitation-sedation-scale-rass 

MANAGEMENT

• Correct the correctable
• Treat the underlying cause
• If urinary retention, consider catheterization
• If any biochemical imbalance, consider correction
• If nicotine withdrawal, use TD nicotine patches
• If alcohol or benzodiazepine withdrawal, then consider benzodiazepine
• Non-pharmacological measures
• Use a multi-disciplinary approach
• Assess and record the wishes of patient and family
• Adequate communication between the doctor, patient, and family on physical, psychological, social and existential/ spiritual issues and the pros and cons of therapeutic palliative sedation should be done in advance, if palliative sedation is considered a possible intervention necessary in the future
• Clearly document in detail the communication with patient/family
• Pharmacological measures
Start with Midazolam
• Intermittent sedation
• Inj. Midazolam 2.5-5mg (max 10mg) S/C stat and q1h prn
• Continuous sedation
• Inj. Midazolam 10-60mg/24 hours CSCI
• Reported upper dose for agitation is 60mg/24 hours
If Midazolam alone is not effective at doses above 60mg/24 hours (terminal agitation), then add
• Haloperidol 5mg S/C stat, and 10-30mg/24 hours CSCI
If above is not effective, then consider phenobarbital
• Start with loading dose of 200mg (1mL ampoule) as:
• undiluted intramuscular injection or
• diluted intravenous bolus given over 2min (1mL ampoule diluted to 10mL with water for injection)
• If agitation persists, give 1 or 2 further doses of 200mg IM/IV prn 30 minutes apart
• If agitation persists or recurs, give further doses of 200mg IM/IV q1h prn
• Maintain with 800mg/24 hours CSCI; or more if total initial dose necessary to control was ≥600mg
• If necessary, increase the dose progressively to 1,600mg/24 hours, i.e. 800mg→1,200mg→1,600mg
• A typical dose is 800–1,200mg/24 hours but can range 200–1,600mg/24 hours
Alternatively
• Consider Chlorpromazine 25mg q4h escalating to 200mg/24 hours PR or S/L

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REFERENCES

• Adam, J. (2006). The last 48 hours. ABC of Palliative Care (pp. 44-47)
• Krakauer, E.L. (2015). Sedation at the end of life. Oxford Textbook of Palliative Medicine (pp. 1134-1142)
• Nogueira, F.L. and Sakata, R.K. Palliative Sedation of Terminally Ill Patients. Brazilian Journal of Anaesthesiology.(2012); 62(4): 580-592
• Olsen, M.L., Swetz, K.M., Mueller, P.S. Ethical Decision Making With End-of-Life Care: Palliative Sedation and Withholding or Withdrawing Life-Sustaining Treatment. Mayo Clinic Proceedings. (2010); 85(10):949-954
• Twycross, R., Wilcock, A., Howard, P. (2014). Drug treatment in the imminently dying. Palliative Care Formulary 5. (pp. 822-823)
• Twycross, R., Wilcock, A., Howard, P. (2014). Central nervous system – Benzodiazepines. Palliative Care Formulary 5. (pp. 214-215)
• Twycross, R., Wilcock, A., Howard, P. (2014). Central nervous system – Phenobarbital. Palliative Care Formulary 5. (pp. 383)