Cost-Effectiveness of α2 Agonists for Intravenous Sedation in Patients With Critical Illness

JAMA Netw Open. 2025 May 1;8(5):e2517533. doi: 10.1001/jamanetworkopen.2025.17533.

Abstract

Importance: Propofol and the α2 agonists dexmedetomidine and clonidine are used for sedation in patients with critical illness receiving mechanical ventilation. Evidence about the cost-effectiveness of intravenous (IV) sedation with these medications is lacking.

Objective: To investigate the cost-effectiveness of dexmedetomidine-, clonidine-, and propofol-based IV sedation in patients with critical illness receiving mechanical ventilation.

Design, setting, and participants: This economic evaluation used within-trial cost-utility analysis with a 6-month time horizon comparing dexmedetomidine-, clonidine-, and propofol-based IV sedation from a UK National Health Service and Personal Social Services perspective, with individual-level data collected from the Alpha 2 Agonists for Sedation to Produce Better Outcomes From Critical Illness (A2B) trial. Adults with critical illness receiving mechanical ventilation, with an anticipated total requirement for mechanical ventilation of at least 2 days, from 41 intensive care units in the UK were included. Recruitment ran from December 2018 through October 2023; the last date of follow-up was December 10, 2023.

Interventions: Dexmedetomidine, clonidine, or propofol IV sedation. Patients receiving α2 agonists were permitted to receive supplemental propofol to achieve the target sedation score if required.

Main outcomes and measures: Incremental costs and quality-adjusted life years (QALYs) gained between dexmedetomidine-based vs propofol-based and clonidine-based vs propofol-based IV sedation were assessed. Mean net monetary benefits with each medication were assessed.

Results: Among 1404 adults with critical illness receiving mechanical ventilation (mean [SD] age, 59.2 [14.9] years; 901 male [64.2%]), the mean (SD) Acute Physiology and Chronic Health Evaluation (APACHE) II score was 20.3 (8.2). The incremental cost for dexmedetomidine vs propofol was $1273 (95% CI, -$5000 to $7545), and for clonidine vs propofol, it was -$1328 (-$7114 to $4459). For dexmedetomidine vs propofol, there were 0.0008 QALYs (95% CI, -0.0198 to 0.0214 QALYs) gained, and for clonidine vs propofol, there were -0.0019 QALYs (95% CI, -0.0221 to 0.0181 QALYs) gained. Mean net monetary benefits for dexmedetomidine, clonidine, and propofol were -$53 278 (95% CI, -$58 063 to -$48 493), -$50 882 (95% CI, -$55 003 to -$46 762), and -$52 036 (95% CI, -$56 230 to -$47 834), respectively, at a maximum willingness to pay for a QALY of $16 250.

Conclusions and relevance: In this study, dexmedetomidine-, clonidine-, and propofol-based IV sedation in patients with critical illness receiving mechanical ventilation had similar costs and QALYs. These findings suggest that economic considerations should not affect which sedative these patients receive.

MeSH terms

  • Administration, Intravenous
  • Adrenergic alpha-2 Receptor Agonists* / administration & dosage
  • Adrenergic alpha-2 Receptor Agonists* / economics
  • Adrenergic alpha-2 Receptor Agonists* / therapeutic use
  • Adult
  • Aged
  • Clonidine* / administration & dosage
  • Clonidine* / economics
  • Clonidine* / therapeutic use
  • Cost-Benefit Analysis
  • Critical Illness* / economics
  • Critical Illness* / therapy
  • Dexmedetomidine* / administration & dosage
  • Dexmedetomidine* / economics
  • Dexmedetomidine* / therapeutic use
  • Female
  • Humans
  • Hypnotics and Sedatives* / administration & dosage
  • Hypnotics and Sedatives* / economics
  • Hypnotics and Sedatives* / therapeutic use
  • Male
  • Middle Aged
  • Propofol* / administration & dosage
  • Propofol* / economics
  • Propofol* / therapeutic use
  • Quality-Adjusted Life Years
  • Respiration, Artificial / economics
  • United Kingdom

Substances

  • Dexmedetomidine
  • Clonidine
  • Propofol
  • Adrenergic alpha-2 Receptor Agonists
  • Hypnotics and Sedatives