Lesson 3 of 4
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Sedation Agents and Strategies

Riszel March 9, 2022

Commonly Used Sedative Agents

  • Propofol
  • Dexmedetomidine
  • Ketamine
  • Benzodiazepines

Sedative Agents

MoA Onset Duration Precautions AE PK Dose
Propofol GABAA

Na channel

Reduction of glutamate release

1 minute Single bolus dose: 5-6 minutes

Short term use: 0.5-1 hours

Long term use: 25-50 hours




renal failure,



depression, hypotension,



Hepatic conjugation, 2B6 CYP substrate 5–50 mcg/kg/min
Dexmedetomidine Alpha adrenergic agonist 20-30 minutes 1-2 hours Hepatic failure, bradycardia Hypotension,


Hepatic by glucuronidation and renal excretion,

2A6 CYP substrate




MoA Onset Duration Precautions AE PK Dose
Benzodiazepines GABAA 3-10 minutes 2-8 hours Delirium

Midazolam: Hepatic failure

Lorazepam: Renal failure

Metabolic acidosis, propylene

glycol toxicity (lorazepam)

Lorazepam: hepatic conjugation

Midazolam: phase I hepatic to alpha hydroxymidazolam, 3A4

Lorazepam bolus dose:

1–4 mg IV

every 4–6 hours

Midazolam: 1-5 mg/hour

Ketamine NMDAR antagonist 0.5-1 minute 15 minutes Dissociative anesthesia

(2Cs + 2As)

Breathing difficulties, laryngospasm, increases salivary secretions Hepatic N-demethylation by 3A4 to norketamine 1-2 mcg/kg/hour

2018 PADIS Recommendations

  • “We suggest using light sedation (vs deep sedation) in critically ill, mechanically ventilated adults”
  • “We suggest using propofol or dexmedetomidine over benzodiazepines (midazolam or lorazepam) for sedation in critically ill mechanically ventilated patients”
  • “We suggest using propofol over benzodiazepines (midazolam or lorazepam) for sedation in mechanically ventilated patients after cardiac surgery”

Light vs. Deep Sedation/MENDS2 and Sepsis Patients

  • Dexmedetomidine (0.2-1.5 mcg/kg/hr) vs propofol (5-50 mcg/kg/min)
  • No difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (OR 0.96; 95% CI, 0.74 to 1.26)
  • Ventilator-free days (OR 0.98; 95% CI, 0.63 to 1.51)
  • Death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52)


  • Light sedation when appropriate
  • Deep sedation if:
    • Neuromuscular blockade
    • Intracranial hypertension
    • Severe respiratory failure
    • Refractory status epilepticus


  • Prospective, randomized, double blind
  • MICU/SICU patients on ventilator >24 hours
  • 106 patients
  • Dexmedetomidine (DEX) infusion vs lorazepam infusion


  • Prospective, randomized, double blind
  • Included 297 adult patients expected to be on mechanical ventilation for ≥72 hours
  • Dexmedetomidine vs midazolam

Benzodiazepine vs. Nonbenzodiazepine

  • Meta-Analysis of 6 randomized clinical trials
  • Medical and surgical ICU patients on mechanical ventilation receiving intravenous sedation
  • Benzodiazepine vs a nonbenzodiazepine


  • Adult ICU patients needing midazolam or propofol infusion for at least 24 hours
  • Midazolam infusion for 249 patients (MIDEX)
  • Propofol infusion for 251 patients (PRODEX)


  • Dexmedetomidine

How to Put this Into Clinical Practice

  • Treat pain, treat pain, then treat pain
  • Remove reasons for irritation and agitation
  • Determine your KEYSTONE sedative agent:
    • Level and duration of sedation
    • Other disease states, such as, seizure? Pancreatitis? Allergy? Elevated intracranial pressure? Severs ARDS?
  • Clinical factors:
    • Blood pressure, heart rate, ventilation status (approaching extubation?)
  • Organ dysfunctions:
    • Renal and hepatic
  • Withdrawal:
    • Alcohol, home benzodiazepines