What medications are used for medically assisted dying (euthanasia)?

Medications Used for Medical Aid in Dying

The primary medications used for medically assisted dying include barbiturates (particularly pentobarbital and phenobarbital), benzodiazepines (midazolam), neuroleptics (levomepromazine, chlorpromazine), and anesthetic agents (propofol), though barbiturates remain the most commonly employed agents for achieving rapid unconsciousness and death. 1, 2

Primary Drug Classes

Barbiturates (First-Line Agents)

Barbiturates are the most widely used medications for assisted dying due to their reliable ability to cause unconsciousness and death. 1, 2

• Pentobarbital is the most common agent used in jurisdictions where medical aid in dying is legal 3, 1

  • Typical lethal dose: 2-10 grams orally 4
  • Death typically occurs within 15-30 minutes of ingestion 4
  • Lethal blood concentration averages around 30 mg/L, though concentrations of 15-40 mg/L are considered compatible with death 5
  • Mechanism: causes CNS and respiratory depression progressing to coma, respiratory arrest, and death 5

• Phenobarbital is an alternative barbiturate option 6

  • Dosing: 1-3 mg/kg IV or subcutaneous bolus, followed by infusion of 0.5 mg/kg/h 6
  • Usual maintenance: 50-100 mg/h 6
  • Advantages: rapid onset, anticonvulsant properties 6
  • Lethal blood level: 100-200 mg/L 5

Benzodiazepines

Midazolam is frequently used, particularly in combination protocols 6

• Starting dose: 0.5-1 mg/h continuous infusion, with 1-5 mg boluses as needed 6
• Usual effective dose: 1-20 mg/h 6
• Advantages: rapid onset, can be administered IV or subcutaneously, compatible with opioids 6
• Mechanism: short-acting benzodiazepine that rapidly penetrates CNS but requires continuous infusion due to rapid redistribution 6

Neuroleptics/Antipsychotics

These agents may be used as adjuncts, particularly when delirium is present 6

• Levomepromazine: 12.5-25 mg starting dose, up to 300 mg/day continuous infusion 6
• Chlorpromazine: 12.5 mg IV/IM every 4-12 hours, or 25-100 mg rectally 6

Anesthetic Agents

Propofol offers rapid, titratable unconsciousness 6

• Loading dose: 20 mg, followed by infusion of 50-70 mg/h 6
• Advantages: very short duration of action and rapid onset, making it easy to titrate 6
• Note: no analgesic effect; opioids necessary if pain is present 6

Critical Clinical Considerations

Efficacy and Safety Concerns

Current evidence reveals significant complications with assisted dying protocols, including failure rates that raise concerns about humane death. 1, 2

• Vomiting occurs in up to 10% of cases 1
• Prolongation of death up to 7 days has been reported 1
• Re-awakening from coma occurs in up to 4% of cases, representing failure of unconsciousness 1
• Wide variety of lethal drug combinations are used with unclear modes of action 2

Method Variations by Jurisdiction

Self-administered barbiturate ingestion is the common method in US states and some European countries, while physician-administered injections (combining general anesthetic and neuromuscular blockade) are used in Dutch protocols. 1, 7

• Voluntary assisted dying typically involves self-administered oral barbiturates 1
• Death results slowly from asphyxia due to cardiorespiratory depression 1
• Physician-administered protocols may combine multiple drug classes 1

Important Caveats

Barbiturate overdose can be survived with aggressive supportive care, even at lethal concentrations. 4

• Case reports document survival after ingestion of 20 grams pentobarbital with peak serum levels of 116 mg/L (nearly 4 times typical lethal concentration) 4
• Early CPR and prolonged cardiorespiratory support in ICU can reverse otherwise fatal overdoses 4
• Assessment of brainstem death should be deferred until adequate drug elimination 4

Regulatory Context

Medical aid in dying is currently legal in nine US states and the District of Columbia, with specific eligibility requirements and physician participation being voluntary. 3, 7

• Key condition: explicit and voluntary patient request 7
• Requirement: severe suffering from incurable medical condition where hastening death is the only means to address suffering 7
• Physicians can choose not to participate and many are prohibited by employers 3

Monitoring and Data Collection

Current monitoring of assisted dying drug protocols is inadequate, with often very low clinician reporting rates. 2

• Little attention has been given to unmonitored prescribing of lethal drug combinations 2
• More thorough data collection regarding drugs used must be implemented 2
• Research is urgently needed into mode of action of drug combinations 2