Intensive Care Unit Sedation (see Sedation, [[Sedation]])
Clinical Efficacy
Dexmedetomidine (Precedex) Compared to Midazolam (Versed) (2009) (see Dexmedetomidine, [[Dexmedetomidine]] and Midazolam, [[Midazolam]]) [MEDLINE]
Dexmedetomidine is Similarly Effective for Sedation, as Compared to Midazolam
Dexmedetomidine Shortened the Time to Extubation, as Compared to Midazolam
Dexmedetomidine was Associated with Less Delirium, as Compared to Midazolam
Dexmedetomidine was Associated with Less Tachycardia/Hypotension, but More Bradycardia, as Compared to Midazolam
Dexmedetomidine (Precedex) Compared to Midazolam (Versed) (2010) (see Dexmedetomidine, [[Dexmedetomidine]] and Midazolam, [[Midazolam]]) [MEDLINE]
Dexmedetomidine Resulted in Less Cost in the ICU, as Compared to Midazolam: due to decreased length of ICU stay and decreased ventilator days
MIDEX and PRODEX Trials: Dexmedetomidine (Precedex) Compared to Midazolam (Versed) and Propofol (Diprivan) (2012) (see Dexmedetomidine, [[Dexmedetomidine]], Midazolam, [[Midazolam]], and Propofol, [[Propofol]]) [MEDLINE]: data from randomized MIDEX (Midazolam vs. Dexmedetomidine) and PRODEX (Propofol vs. Dexmedetomidine) trials
Dexmedetomidine was Equivalent in Maintaining Light-Moderate Sedation
Dexmedetomidine Decreased the Duration of Mechanical Ventilation, as Compared to Midazolam (But Not When Compared to Propofol)
Dexmedetomidine Improved Patients’ Ability to Communicate Pain, as Compared with Midazolam and Propofol
Dexmedetomidine Demonstrated More Adverse Effects (Bradycardia/Hypotension), as Compared with Midazolam and Propofol
In the First 24 hrs of PRODEX Trial, Discontinuation of Dexmedetomidine was More Frequent Due to Lack of Efficacy: this suggests that adequate sedation may not be possible in all patients with dexmedetomidine alone (and it is likely that dexmedetomidine is not equivalent to propofol)
Comparison of Non-Benzodiazepine Sedation (Dexmedetomidine, Propofol) vs Benzodiazepine Sedation in Mechanically Ventilated ICU Patients (Crit Care Med, 2013) [MEDLINE]
Use of Dexmedetomidine/Propofol-Based Sedation Regimen Decreased ICU Length of Stay and Duration of Mechanical Ventilation, as Compared to a Benzodiazepine-Based Regimen
Propofol (Diprivan) Compared to Midazolam/Lorazepam (2014) (see Propofol, [[Propofol]], Midazolam, [[Midazolam]], and Lorazepam, [[Lorazepam]]) [MEDLINE]
Propofol Decreased Mortality Rate, as Compared to Benzodiazepines (Midazolam/Lorazepam)
Propofol Increased Probability of ICU Discarge at 28 Days, as Compared to Benzodiazepines (Midazolam/Lorazepam)
Propofol Decreased Ventilator Days at 28 Days, as Compared to Benzodiazepines (Midazolam/Lorazepam)
Benzodiazepines are GABA-A Receptor Agonists: bind to post-synaptic receptors on GABA neurons in the central nervous system (limbic system, reticular formation)
GABA has an Inhibitory Effect
Pharmacokinetics
Midazolam is Lipophilic: rapidly crosses the blood brain barrier
Onset of Action (IV Dose): 2-5 min
Peak Effect (IV Dose): 5-7 min
Half-Life: 3-11 hrs (Typical Range: 1.8-6.4 hrs)
Prolonged Infusion Results in Accumulation of the Active Metabolite
Half-Life is Prolonged in Cirrhosis, Congestive Heart Failure, Obesity, Renal Failure, and the Elderly
Metabolism
Hepatic Oxidation (CYP3A4): 60-70% is 1-Hydroxy-Midazolam (Active Metabolite) or Alpha-Hydroxymidazolam
Renal Excretion of 1-Hydroxy-Midazolam (Active Metabolite) and Alpha-Hydroxymidazolam
Administration
PO
Intranasal
IV (Load): 1-5 mg
IV (Maintenance): 1-5 mg/hr
Dose Adjustment
Hepatic: use with caution in liver disease (due to prolonged duration)
Renal: although no dose adjustment is specified in manufacturer labeling, renal failure patients on a continuous midazolam infusion are unable to eliminate the active metabolite 1-hydroxymidazolam, resulting in accumulation and prolonged sedation after discontinuation (sometimes for days)