Chapter 34: Application of Pharmacokinetic and Pharmacodynamic Modeling to Guide Propofol Administration for Endoscopy Procedures

INTRODUCTION

Sedation for endoscopy is a rapidly emerging endeavor in anesthesia. Growth in this area has been steady, and anesthesiologists are increasingly becoming involved in endoscopic sedation. Endoscopy is distinguished from other anesthetic challenges by 2 factors. First, these procedures are performed with natural airways, and excessive sedation may induce obstruction and respiratory depression. Second, the procedure time is short, and there is insufficient time to tune the anesthetic. These factors affect the anesthetic strategy. Anesthesiologists assume that the skills learned in the operating room transfer to the endoscopy suite, but a bolus of propofol sufficient for a 99% probability of obtunding response to intubation may exceed the total propofol requirement for a diagnostic esophagogastroduodenoscopy (EGD) several times and result in a prolonged period of jaw thrust to overcome obstruction. Conversely, starting a propofol infusion at the infusion rate for maintenance of loss of consciousness will take a considerable period of time to achieve this outcome. Target-controlled infusion (TCI) may achieve a specified effect-site concentration reliably, but the variability of patient response complicates the selection of the target.¹ Thus, in a relatively short encounter, anesthesiologists must pick the appropriate induction dose for deep sedation and from this infer the proper maintenance dose.

Experienced clinicians use a number of strategies, but these can be divided into 2 broad camps based on whether an infusion pump or a handheld syringe is employed in titration. This chapter will present 2 strategies that use a pharmacokinetic model of propofol with little more than a few bits of information, a watch, and a calculator. This model enables anesthesiologists to optimize sedation and analgesia for EGD procedures that rivals the performance of real-time optimal control algorithms. It is important to recognize that these techniques are not a substitute for years of experience or sophisticated monitoring technology. Rather, they represent an application of drug simulation at the point of care that permits a novice to consistently “hit the dartboard.”

Simulations will be used to illustrate the 2 dosing strategies. These simulations will utilize a propofol 3-compartment pharmacokinetic model introduced by Cortinez et al.² This model permits consideration of increasing weight without the problems associated with the high body mass indices encountered in earlier models of propofol pharmacokinetics. The model parameters are included in Table 34–1.

Compartment volumes are scaled by weight/70 kg, and clearances by weight/70 kg raised to the 0.75 power (referred to as allometric scaling). Age corrections are applied to model parameters V2 and Q2, as indicated in Equations 34–1 and 34–2.