Pharmacology of Commonly Used Analgesics and Sedatives in the ICU: Benzodiazepines, Propofol, and Opioids
Section snippets
Pharmacologic principles guiding the use of analgesics and sedatives in the critically ill
Several important pharmacologic principles are crucial when formulating an analgesic and sedative regimen in patients who are critically ill. The two pharmacokinetic parameters that will affect the drug response and safety most are volume of distribution (Vd) and clearance. Vd describes the relationship between the amount of drug in the body and the concentration in the plasma after absorption and distribution are completed. Vd is affected by body size, tissue binding, plasma protein binding,
Analgesics
Opioid analgesic medications remain the mainstay of therapy for alleviating pain in the ICU patient.1, 2 This class of agents is also frequently used because of its sedative properties and to facilitate mechanical ventilation given its potent respiratory depressant effects. Neither acetaminophen nor the nonsteroidal antiinflammatory agents are discussed in this article given their weak analgesic activity and their propensity to cause adverse effects in patients who are critically ill.2
Benzodiazepines
Benzodiazepines (eg, diazepam, lorazepam, midazolam) remain the most commonly administered class of sedatives for patients in the ICU given their potent anxiolytic, sedative, and hypnotic effects (Table 3). These observed pharmacologic effects depend on the degree to which the benzodiazepine binds to the GABA receptor, with 20% binding associated with anxiolysis, 30%–50% with sedation, and 60% with hypnosis.53 Although benzodiazepines induce anterograde amnesia, they do not cause retrograde
Summary
The ideal sedative or analgesic agent should have a rapid onset of activity, a rapid recovery after drug discontinuation, a predictable dose response, a lack of drug accumulation, and no toxicity.96 Unfortunately, none of the earlier analgesics, the benzodiazepines, or propofol share all of these characteristics. Patients who are critically ill experience numerous physiologic derangements and commonly require high doses and long durations of analgesic and sedative therapy. There is a paucity of
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