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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.59 no.1 Campinas Jan./Feb. 2009
LETTERS TO THE EDITOR
of remifentanil vs. sufentanil in videolaparoscopic surgeries. A comparative
(Rev Bras Anestesiol, 2008; 58:193-20)
To the Chief Editor of the Brazilian Anesthesiology Journal
Dr. Judymara Lauzi Gozzani
We are sending this letter to the Editor of the RBA to rescue some considerations on the article "Continuous Infusion of Remifentanil vs. Sufentanil in Videolaparoscopic surgeries. A Comparative Study" published on Rev Bras Anestesiol, 2008; 58:193-20, as well as in relation to the reply of the author, Dr. Ricardo Simoni, published on Rev Bras Anestesiol, 2008; 58:548-555.
After several e-mails between Drs. Fernando Nora and Ricardo Simoni, we decided to send you a letter signed by both of us to correct a flaw in the interpretation of the data of that study. During the phase of determination of the maximal plasma concentrations of remifentanil for the period of the infusion described in the original article, questioned by Dr. Fernando Nora and reaffirmed in the reply of Dr. Ricardo Simoni, the author acknowledges an error in the simulation and that the simulation determining a maximal plasma concentration of 7.8 ng/ml-1 is the right one, resulting on a potency ratio between sufentanil and remifentanil of 1:13 and not 1:18, as stated in the article and the reply. The error occurred because the author used the data of the model of the remifentanil infusion pump described by Minto et al. for a mechanical infusion pump, changing only the weight, in kg, by the "lean weight mass" (LWM). Therefore, equipotent forms of sufentanil and remifentanil were used supporting the thesis that sufentanil was not more synergic than remifentanil when associated to propofol in that study.
But the pharmacological model of Minto et al. 1 describes several changes in the administration and management of the remifentanil target-controlled infusion pump besides those acknowledged by Dr. Ricardo Simoni. One of the changes is the use of the lean mass index (based on the weight informed) to calculate pharmacokinetic parameters that depend on the weight, such as the volume of distribution in the central compartment. Other changes in the management and calculus of the flow of remifentanil as a function of time depend on gender, age, height, and, especially, calculus of intracompartmental exchanges, which are dynamic. This refers to the rate constants (K12, K13, K31...) whose analysis obeys an exponential and not a linear equation. For this reason, mechanical pumps (µg.kg-1.min-1) cannot mimic target controlled pumps, even when the lean weight is used to calculate the infusion doses, because in the time domain, through the calculus of intracompartmental exchanges, the flow of the pump has to change constantly, making it impossible for a person to calculate it the same way this equipment does. Thus, calculating the LBM without the other changes, and introduce it in the mechanical pump can generate plasma concentrations well below those desired. For example: If I want to use 0.3 µg.kg-1.min-1 in a 74-kg patient with a mechanical infusion pump, I should inform the same 74 kg to the pump (except in obese individuals) and not the lean weight, since this equipment does not correct the infusion dose according to the three compartments model. In those cases, the pump uses the following equation: 0.3 x 74 = 22.2 µg.min-1. Thus, if I inform the lean weight (50 kg) of the same patient instead of the real weight the pump will administer a lower infusion, i.e., 0.3 x 50 = 15 µg.min-1. A reduction greater than 30% in the total mass of drug administered. The reasoning to determine plasma concentrations achieved changes when compared with the mechanical infusion because the flow of the pump changes constantly according to the calculations of intracompartmental exchange of drugs. This is known as optimization of drugs present in compartments other than the effector site. For this reason, mean infusions in two similar mechanical infusion pumps do not always achieve equally similar concentrations. But two target-controlled pumps regulated to achieve similar plasma concentrations will assure that the plasma concentrations are similar, each one with the margin of error described with different drugs, pharmacological model used, and clinical situation!
Summarizing, the determination of the plasma concentration of a drug does not depend only on the weight and lean body mass, but of those two factors along with all the others that cause dynamic changes in the continuous calculation of drug infusion when a target-controlled pump is used. This is a classical example in which the hand of science with the advent of the computer is infinitely more precise than man. The art of Medicine resides on the interpretation of clinical data and pump management; here we are untouchable and invincible!
Dr. Fernando Squeff Nora, TSA/SBA
Dr. Ricardo Simoni, TSA/SBA
01. Minto C, Thomas W, Egan T Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil: I. Mode. Anesthesiology, 1997;86:10-23. [ Links ]