To the Editor:-Computer-assisted infusion devices are open loop control systems that allow the anesthesiologist to select the target blood or plasma concentration or, in some patients, the target effect site concentration likely to be required to achieve a particular pharmacodynamic effect. Depth of anesthesia then is controlled by the anesthesiologist, making adjustments to the target setting as required for each patient.

All such systems require a microprocessor-controlled infusion pump programmed with infusion rate control algorithms linked to a pharmacokinetic simulation program. The program includes a pharmacokinetic model and a specific set of pharmacokinetic parameters for the drug to be infused. Individual academic groups have referred to this technology by a variety of acronyms, including CATIA (computer-assisted total intravenous anesthesia), [1] TIAC (titration of intravenous agents by computer), [2] CACI (computer-assisted continuous infusion), [3] and CCIP (computer-controlled infusion pump). [4] The term, target-controlled infusion, (TCI) also has been used in this context. [5] Although TCI covers the concept common to all the previous systems, it avoids implying that a computer rather than an anesthesiologist is controlling the depth of anesthesia. Additionally, commercial TCI systems will not likely require an external computer.

In using and describing any TCI system, there is a need for consistent terminology to identify the drug concentration described, the site at which this concentration is determined, and the pharmacokinetic parameters used in the system. The TCI system should display the target concentration that has been set by the user (CT) and the concentration that the TCI system calculates will have been achieved (C sub CALC). CCALCis preferred to CP(predicted concentration) to prevent confusion with CP(plasma concentration). In assessing the predictive performance of TCI systems, drug concentrations are measured (C sub M) and compared with CCALC. [6]

In many cases, the site at which a particular concentration is determined is obvious and always should be mentioned in any article. Where there is a need to specify the site, the previous terminology can be expanded as follows:

CpT= target plasma concentration;

CeT= target effect site concentration;

CpM= measured plasma concentration;

CpCALC= calculated plasma concentration; and

CeCALC= calculated effect-site concentration.

The time course and magnitude of the pharmacodynamic response achieved at a given CTwill be influenced by the pharmacokinetic parameters incorporated in the system used. [7] Thus, whenever a target or calculated concentration is given in a manuscript, authors should ensure that they provide information on the pharmacokinetic model and parameter set used. When many models are being used, the use of a second subscript to identify the pharmacokinetic parameter set used would be unambiguous, e.g., CpCALCMAITRE= calculated plasma concentration based on pharmacokinetic parameters published by Maitre, et al. [8]

In relating pharmacodynamic effects to drug concentrations, Cp50 has been used as the measured plasma concentration (Cp50M), at which there is a 50% probability of suppressing a response to a certain stimulus. [9] This will continue to be an important index because Cp50 sub M will be independent of the device used. In clinical research and routine clinical experience with TCI systems, wherein information on measured concentrations may not be available, observations based on CCALCdisplayed by the TCI system when a particular effect is observed may be of more value to a clinician. Ideally, Ce50CALCor Ce90CALC(with the PK/PD model specified in the text) should be the index used, but CP50CALCor CP90CALCmay be suitable alternatives, with the important proviso that the calculated plasma concentration has been maintained for a sufficient period to permit equilibration with the effect site.

P. S. A. Glass, M.D.

Associate Professor of Anesthesia, Duke University Medical Center, Durham, North Carolina

J. B. Glen, Ph.D.

Clinical Specialist, Medical Affairs Department; Zeneca Pharmaceuticals

Alderley Park; Macclesfield SK10 4TG; United Kingdom

G. N. C. Kenny, M.D.

Professor of Anaesthesia; University of Glasgow; Glasgow, United Kingdom

J. Schuttler, M.D.

Professor of Anaesthesia; University of Erlangen-Nuremberg; Erlangen, Germany

S. L. Shafer, M.D.

Assistant Professor of Anesthesia; Stanford University; Stanford, California

(Accepted for publication March 26, 1997.)

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