What is the role of benzodiazepines in procedural sedation and analgesia (PSA)?

Updated: Sep 21, 2020
  • Author: Alma N Juels, MD; Chief Editor: Erik D Schraga, MD  more...
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Benzodiazepines elicit beneficial effects for PSA that include amnesia, anticonvulsant, anxiolysis, and sedation. Benzodiazepines potentiate gamma-aminobutyric acid (GABA) inhibitory action in the CNS by binding to benzodiazepine-specific receptors on the GABAA -benzodiazepine receptor complex. Binding of this complex potentiates GABA-mediated chloride influx that results in sedation, amnesia, anxiolysis, and anticonvulsant effects and respiratory depression.

Midazolam is the benzodiazepine most commonly used for PSA, since it produces a faster onset of sedation, more complete amnesia, less pain on injection, and improved awakening when compared with diazepam. Midazolam possesses a relatively high volume of distribution (Vd) compared with other benzodiazepines because of its lipophilicity. The Vd is greatly amplified in obese patients, resulting in an increased half-life from 2.7 hours to 8.4 hours. Midazolam is cleared by hepatic hydroxylation to 1-hydroxymidazolam (elicits about 10% of the pharmacologic activity as parent compound). In comparison, diazepam has an extremely long half-life (0.8-2.25 d) that is markedly increased in obese or elderly patients (3.9 d and 3.29 d, respectively). Additionally, its active metabolites have long half-lives(ie, N -desmethyldiazepam[1.6-4.2 d]; nordazepam [about 8 d]).

Lorazepam (Ativan) is another benzodiazepine that may be used for mild-to-moderate sedation; however, unlike midazolam, its onset of action does not peak until 15-20 minutes after administration. The duration of action of lorazepam is longer (ie, 6-8 h) than that of midazolam (30-60 min). In addition, lorazepam has roughly double the potency of midazolam and lack of metabolite activity. Because of this, lorazepam is typically used for long-term sedation, such as in an ICU setting.

When combined with alcohol or opioids, the sedative and respiratory-depressant effects of benzodiazepines are greatly increased, as is the risk for cardiovascular depression.

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