Abstract
Anesthesia is a combination of unconsciousness, amnesia, and analgesia, expressed in sleeping patients by limited reaction to noxious stimulations. It is achieved by several classes of drugs, acting mainly on central nervous system. Compared to other therapeutic families, the anesthetic drugs, administered by intravenous or pulmonary route, are quickly distributed in the blood and induce in a few minutes effects that are fully reversible within minutes or hours. These effects change in parallel with the concentration of the drug, and the concentration time course of the drug follows with a reasonable precision mathematical models based on the Fick principle.Therefore, understanding concentration time course allows adjusting the dosing delivery scheme in order to control the effects. The purpose of this short review is to describe the basis of pharmacokinetics and modeling, the concentration-effects relationship, and drug interactions modeling to offer to anesthesiologists and non-anesthesiologists an overview of the rules to follow to optimize anesthetic drug delivery.
Highlights
Anesthesia is a complex state including several reversible therapeutic effects such as loss of consciousness and recall or lack of response to variable noxious stimulations coming from surgery or anesthetic management
Others are quantal, such as being asleep or the absence of movement response to surgical incision. The probability of these quantal effects increases with the dose. This is true for adverse effects, they usually occur at higher doses than therapeutic effects
Drug dosages should be chosen to maintain the patient inside a therapeutic window, and dosing should be large enough to achieve therapeutic effects but small enough to avoid late recovery or adverse effects
Summary
Anesthesia is a complex state including several reversible therapeutic effects such as loss of consciousness and recall or lack of response to variable noxious stimulations coming from surgery or anesthetic management. The patient’s pharmacological status, based on estimated effect-site opioid and hypnotic drug concentrations, can be displayed in relation to these isoboles in real time as well as in the past and the near future (Figure 4) This display, designed to help physicians to adjust drug delivery, may be useful to predict the response to noxious stimulations, whereas EEG monitoring predicted better the degree of sedation[42]. The authors showed that, after two measures, only minor changes in the PK model were observed, suggesting that the intra-individual variability is low compared with inter-individual variability In the future, this kind of algorithm may be used in many contexts, such as to adapt propofol PK to online measured concentrations or to real-time EEG effect, especially in patients who are likely very far from the population model (such as those with cardiac failure, obesity, or various organ failures in intensive care). It requires no PKPD model but may oscillate around the target value, is delayed in case of abrupt variations, and may become erratic if no measured value is available because of artifacts[45]
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