Introduction     Fast Fact #106 reviewed the decision process and patient selection considerations for controlled sedation for refractory suffering at the end-of-life. This Fast Fact will review best practices for the medical administration of controlled sedation.

Prior to initiating sedation

• Ensure a thorough discussion of the proposed treatment plan and expected outcomes has occurred with patient (if able), all family members, and all medical staff (prescribing clinicians, nurses, therapists, pharmacists, nursing aides, chaplain, etc.). Make sure all are on the same page.
• Review plans for artificially administered nutrition/hydration. Whether it is going to be stopped or continued, ensure this has been discussed and documented with patient/family and the medical team.
• Make sure appropriate treatment limitation orders (e.g., DNR/DNI) are in place.
• Assure a peaceful, quiet setting, with a minimum of intrusions.
• Confirm if any specific goals need to be met prior to starting sedation (e.g., visit from relative).
• Confirm patient/family desire for chaplain/spiritual support prior to starting sedation.
• Review medication and treatment orders. Discontinue orders not contributing to comfort (e.g., vital sign monitoring, blood glucose checks).

Initiating controlled sedation: Many drugs have been used to provide effective sedation; there are no controlled trials comparing efficacy.  Midazolam is most utilized, but propofol, barbiturates, and other benzodiazepines have also been utilized effectively.  There are case reports of dexmedetomidine being used to treat intractable pain and delirium at the end of life, while still preserving some arousability; however future research is needed to compare its effectiveness with standard therapies. Although many patients are on opioids prior to the initiation of controlled sedation, opioids are not effective at maintaining sustained sedation. This is because tolerance to the sedating properties of opioids occurs quickly compared with more standard sedatives.  In general, though, opioids should be continued, along with the sedating drug, to avoid opioid withdrawal and to treat unobserved pain. The following lists starting doses for the use of sedating drugs including the bolus dose and a starting continuous infusion (CI) rate.  The CI rate can be titrated to achieve the desired level of sedation.  SC = subcutaneous, gtt = drip rate. 

• Midazolam (SC, IV):  5 mg bolus, 1 mg/hr gtt.
• Lorazepam (SC, IV):  2-5 mg bolus, 0.5-1.0 mg/hr gtt.
• Thiopental (IV): 5-7 mg/kg/hr bolus, then 20-80 mg/hr gtt.
• Pentobarbital (IV):  1-3 mg/kg bolus, 1 mg/kg/hr gtt;
• Phenobarbital (IV, SC):  200 mg bolus (can repeat q10-15 min), then 25 mg/hr gtt.
• Propofol (IV):  20-50 mg bolus (may repeat), 5-10 mg/hr gtt.

Maintaining sedation: Current hospital monitoring standards for conscious sedation are inappropriate in the dying patient.  A general rule is that the depth of sedation can vary, depending on the symptoms being palliated, and prior discussions with the family regarding goals of treatment.  Generally, the infusion is initiated and then titrated to a point where the patient appears to be comfortable.  Care should be taken to make further adjustments when necessary to facilitate palliative nursing care.  Other reported strategies include varying the depth of sedation during the day, providing deeper sedation at night to ensure peaceful rest.  When sustained sedation to unconsciousness is desired, some authors have recommended that the sedative dose should be titrated to a RASS score of -3 or -4.

Survival: Once total sedation is initiated, survival can be quite variable, but generally is brief.  Muller-Busch reports survival of 63 +/- 58 hrs after initiation of sedation, Sykes reports 56% of patients survived less than 48 hours.

References

1. Berger AM, et al, eds. Principles and Practice of Palliative Care and Supportive Oncology. Philadelphia, PA: Lippincott Williams & Wilkins; 2002.
2. Hallenbeck J, Terminal sedation for intractable distress.  West J Med. 1999; 171(4): 222-3.
3. Muller-Busch H, et al. Sedation in palliative care – a critical analysis of 7 years experience. BMC Palliative Care. 2003; 2(1):2.
4. Hilliard N, Brown S, Mitchinson S. A case report of dexmedetomidine used to treat intractable pain and delirium in a tertiary palliative care unit. Palliative medicine 2015; 29(3): 278-281.
5. Quill TE.  Responding to intractable terminal suffering: the role of terminal sedation and voluntary refusal of food and fluids.  Ann Intern Med. 2000; 132:408-414.
6. Sykes N. Sedative use in the last week of life and the implications for end-of-life decision making. Arch Intern Med. 2003; 163:341-344.
7. Bodnar J. A Review of Agents for Palliative Sedation/Continuous Deep Sedation: Pharmacology and Practical Applications, Journal of Pain & Palliative Care Pharmacotherapy 2017; 31(1):16-37.
8. Arantazamendi M, Belar A, eta l.  Clinical aspects of palliative sedation in prospective studies: a systematic review. Journal of Pain and Symptom Management 2021; 61(4):831-844.

Version History:  originally published in February 2004. 2^nd version in April 2009; 3^rd version edited by Sean Marks MD in June 2015; 4^th edition edited by Sean Marks MD in January 2024.
Conflicts of Interest: None to report.