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Anesthesiology:
doi: 10.1097/ALN.0b013e3182096be5
Correspondence

Presenting Data versus Predictions as Basic Scientific Information: Target-controlled Infusions versus Microgram per Kilogram per Minutes

Bandschapp, Oliver M.D.; Ihmsen, Harald Ph.D.; Koppert, Wolfgang M.D.; Ruppen, Wilhelm M.D.*

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In Reply:

We have read with great interest and also some concern the letter of Dr. Kempen regarding our manuscript.1 To begin with the last point, the problem of discriminating analgesia from other effect-like sedation is discussed in our article. This is a typical problem when studying pain and has been discussed in a recent article on ketamine, where the euphoric effect of the drug interacted with its analgesic effect.2
With regard to Dr. Kempen's main criticism, he is completely right that dose is basic information that should be given in the article. Therefore, we are glad to have the opportunity to supply this information ex post: the total dosage was 4.4 mg/kg in 45 min with a maintenance infusion rate of approximately 90 μg · kg−1 · min−1. However, we do not agree with Dr. Kempen that the predicted/targeted concentrations are not “real.” Of course, these concentrations are predicted values that will differ from measured concentrations. However, if one looks at these concentrations as “targets,” the view changes a bit: for the user, the target concentration set at the target-controlled infusion system is as “real” as the infusion rate set at a normal infusion pump. If one uses a defined system, that means a commercially available target-controlled infusion system with a defined pharmacokinetic parameter set, the information that a defined concentration was targeted is as definite as the information that a defined infusion rate was chosen. This means that any other user may repeat this experiment by using the same system and the same target. On the contrary, if one measures the plasma concentration and reports that a measured concentration c results in an effect E, this information has much scientific impact (it defines a concentration-effect relationship), but for the reader who is interested in clinical information, this is of limited value because he does not know how to achieve this concentration. Moreover, Bruhn et al.3 showed, in a study on propofol pharmacodynamics, that the prediction probability with regard to sedation as measured by the Observer's Assessment of Alertness/Sedation (OAA/S) rating scale was similar for target concentration and measured concentration.
The circumstance that target-controlled infusion is not used in the United States must be considered, and therefore we agree that the infusion rate and not only the target concentration should be reported. However, Anesthesiology is an (maybe “the”) international journal for anesthesiologists worldwide and has a great and long tradition of scientific papers dealing with target-controlled infusion; we would like to cite an editorial by Egan and Shafer4 some years ago in this journal: “How ironic, therefore, that America, the country that brought the world surfing, continues to deny physicians access to the fundamental tools to surf the concentration response curves of intravenous anesthetic agents.”
Oliver Bandschapp, M.D.
Harald Ihmsen, Ph.D.
Wolfgang Koppert, M.D.
Wilhelm Ruppen, M.D.*
* University Hospital Basel, Basel, Switzerland. wruppen@gmail.com
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References

1.Bandschapp O, Filitz J, Ihmsen H, Berset A, Urwyler A, Koppert W, Ruppen W: Analgesic and antihyperalgesic properties of propofol in a human pain model. Anesthesiology 2010; 113:421–8

2.Sigtermans M, Dahan A, Mooren R, Bauer M, Kest B, Sarton E, Olofsen E: S(+)-ketamine effect on experimental pain and cardiac output: A population pharmacokinetic-pharmacodynamic modeling study in healthy volunteers. Anesthesiology 2009; 111:892–903

3.Bruhn J, Bouillon TW, Radulescu L, Hoeft A, Bertaccini E, Shafer SL: Correlation of approximate entropy, bispectral index, and spectral edge frequency 95 (SEF95) with clinical signs of “anesthetic depth” during coadministration of propofol and remifentanil. Anesthesiology 2003; 98:621–7

4.Egan TD, Shafer SL: Target-controlled infusions for intravenous anesthetics: Surfing USA not! Anesthesiology 2003; 99:1039–41

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