Participants 396
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 |
Hypotension,
bradycardia, hepatic/ renal failure, pancreatitis |
Respiratory
depression, hypotension, bradycardia, PRIS |
Hepatic conjugation, 2B6 CYP substrate | 5–50 mcg/kg/min |
| Dexmedetomidine | Alpha adrenergic agonist | 20-30 minutes | 1-2 hours | Hepatic failure, bradycardia | Hypotension,
bradycardia |
Hepatic by glucuronidation and renal excretion,
2A6 CYP substrate |
0.2–0.75
mcg/kg/hr |
| 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
MENDS Study
- Prospective, randomized, double blind
- MICU/SICU patients on ventilator >24 hours
- 106 patients
- Dexmedetomidine (DEX) infusion vs lorazepam infusion
SEDCOM Study
- 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
MIDEX/PRODEX
- 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)
vs.
- 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