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Anesthesiologists recognize the expanding role of premedication in optimizing patient's condition prior to surgery. Important goals of premedication include reducing patient anxiety, providing analgesia as needed, facilitating induction of anesthesia, and optimizing patient comorbidities. This chapter will provide a brief overview of well-known premedication drugs, such as intravenous opioids and benzodiazepines, and explore how they interact with one another and how they may influence induction of anesthesia. This chapter will also review indications, controversies, and potential drawbacks of selected premedications used to manage common patient comorbidities.


Midazolam enjoys wide spread popularity among anesthesiologists because it has a rapid onset of anxiolysis with minimal side effects and provides anterograde amnesia. Midazolam is water-soluble, and unlike diazepam, does not cause irritation on injection. At relatively low doses (0.02 mg/kg), midazolam is an effective anxiolytic over a large age range (20–80 years), with minimal respiratory depression in healthy individuals of either gender.1 Larger doses (0.05 mg/kg) increase the likelihood of sedation but are not more effective at reducing anxiety.1 Elderly debilitated patients require up to 20% less midazolam (0.016 mg/kg) to achieve an equivalent anxiolytic effect.2 For example, patients who have an American Society of Anesthesiologists (ASA) physical classification of 3 or greater and who are of age 55 or older should be dosed with caution.

An advantage of benzodiazepines is they attenuate catecholamine-induced stress response. For example, at doses of 0.025 mg/kg, midazolam attenuates stress responses; at 0.05 mg/kg it abolishes stress responses.3 This may be especially useful in patients with severe coronary artery or cerebral vascular disease who are at significant risk for catecholamine-induced ischemia.

Midazolam has an interesting kinetic profile (Figure 26–1). It has a rapid rise in effect-site concentration with intravenous administration in comparison to other benzodiazepines. However, it requires a relatively long time to reach peak concentrations (6–9 minutes), and plasma concentrations dissipate more slowly in comparison to other intravenous sedatives (eg, propofol). An anxiolytic effect is typically observed within minutes; clinicians may be tempted to administer additional midazolam if an effect is not observed within 2 minutes. Given that peak concentrations are not achieved for up to 6 minutes, additional doses may lead to more pronounced effect. For example, Figure 26–1 presents the anticipated effects from 2 doses of midazolam (0.025 mg/kg or 2 mg to an 80-kg individual) separated by 2 minutes using the Ramsay Sedation Scale (RSS).4 The RSS (range, 0–6) quantifies the effects of midazolam from anxiolysis (RSS = 2) to sedation (RSS = 3) to loss of responsiveness (RSS = 6). The additional midazolam dose prolongs reaching peak to 8 minutes and doubles the effect-site concentration, leading to an increased probability of sedation beyond just anxiolysis.

Figure 26–1

Simulations of midazolam effect-site concentrations (Ce levels) following 2 doses of midazolam (0.025 mg/kg each) separated by 2 minutes. The vertical axis is on ...

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