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Anesthesiologists often consider competing interests when formulating a plan for induction of anesthesia. Of particular concern is the onset and duration of various effects for combinations of anesthetic drugs used in induction. Some questions include:

  • For a rapid-sequence induction, what is the optimal timing of drug administration so that peak effects occur at near the same time?

  • If planning to induce anesthesia in patients with known or suspected difficult manual bag-mask ventilation, what is the duration of apnea and/or ventilatory depression for a given combination of induction agents should manual ventilation become inadequate?

  • Following preoxygenation, what is the anticipated duration of maintaining reasonable oxygen saturations once a patient is rendered apneic?

  • When using a high-dose opioid technique for induction, what dose of sedative–hypnotic provides a near-equivalent effect to a conventional induction technique?

  • What is the role of sugammadex in a failed intubation when a nondepolarizing neuromuscular blocking agent is used?

  • Is it necessary to completely block the response to laryngoscopy and tracheal intubation, or is it reasonable to simply blunt it?

The aim of this chapter is to briefly explore, through simulation, the clinical implications of these questions. The simulations present predictions based on available models of anesthetic drug behavior and human physiology. As with any model-based simulation, the predictions are as good as the models used to make them. When providing a clinical interpretation of the predictions, their assumptions and limitations will be discussed.


A common combined anesthetic induction technique includes fentanyl, propofol, and either succinylcholine or a nondepolarizing neuromuscular blocker such as rocuronium. Given that laryngoscopy and tracheal intubation can be one of the most stimulating events during a surgical procedure, it is useful to maximize the combined analgesic effect of drugs used for induction. A basic understanding of induction drug kinetics can guide the timing of drug administration (Table 28–1). Fentanyl has a different kinetic profile from propofol and succinylcholine. In order for each induction drug to reach maximal effect at nearly the same time, fentanyl 2 to 3 mcg/kg is administered 3 to 4 minutes before propofol.

Table 28–1Predicted time to onset and duration of effect for induction drugs.

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