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LETTERS TO THE EDITOR

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Dear Editor,

In reply to the letter of Dr. Fernando Squeff Nora on our study, I would like to thank him for his comments and critics, as well as to answer some topics to advance the discussion of such intricate and enthusiastic subject.

1. The potency relationship between two drugs is in fact described through the plasma concentration (Cp) capable of generating a measurable clinical effect; among them we can mention the loss of consciousness, reduction of the minimal alveolar concentration of inhalational anesthetics, and prevention of movement with skin incision. The same mass of opioids administered in the same way may lead to different plasma concentrations, especially when the study population has such a wide individual variety: young-old, fat-thin, etc. However, in our study, demographic characteristics (age, gender, weight, and height) in both groups were similar, eliminating or minimizing this discrepancy factor. The simulation of plasma concentrations (Cp) obtained for sufentanil (Bovill's model) and remifentanil (Minto's model) using the mean consumptions described in the study is very enlightening. We are in agreement regarding the maximal sufentanil Cp achieved (0.6 ng.mL

   ^-1). However, we considered that the maximal remifentanil Cp achieved to be 12.6 ng.mL

   ^-1, instead of the concentration suggested by Dr. Nora, 7.8 ng.mL

   ^-1. In our study, the infusion of remifentanil was based on the real weight of the patient. Therefore, to calculate the mean remifentanil Cp, we used the total amount of remifentanil used divided by the real weight of the patient and by the duration in minutes of the infusion, yielding a mean of 0.29 µg.kg

   ^-1.min

   ^-1. However, we are aware that the pharmacokinetic model used in Minto's algorithm for remifentanil uses the lean body weight and, therefore, the maximal Cp achieved was 12.6 ng.mL

   ^-1 and not 7.8 ng.mL

   ^-1, as predicted by our colleague. Consequently, the potency relationship between both opioids would have been 1:21, much closer of the 1:18 proportion indicated in the study as the potency relationship based on the differences of the masses administered. Thus, we continue to say that the infusion schedule of opioids used were not equipotent, justifying the higher values of MAP in the sufentanil group.

2. The concept of synergism between two drugs involves addition mechanisms (1 + 1 = 2) and potentiation (1 + 1 > 2), and in this case the latter causes a higher effect than the simple addition of their separate effects. In our understanding, the critic of our colleague considered only the possibility of an addictive effect between opioids and hypnotics on EEG depression, ignoring the possibility of a potentiation. Among CNS depressants, we have several drugs that when used isolatedly do not have a specific effect in clinical doses, but that "potentiate" this same effect exerted by other drugs used concomitantly. In fact, high Cp levels of remifentanil (10 to 15 ng.dL

   ^-1) and sufentanil (0.5 to 0.75 ng.dL

   ^-1) to cause changes in the EEG. However, we believe in the potentiating synergistic effect when opioids are associated with propofol. Even isolatedly, the maximal Cp obtained with sufentanil was 0.6 ng.mL

   ^-1, well within the margin capable of causing EEG changes in 50% of the patients. Since we used proportionally more remifentanil than sufentanil and obtained the same consumption of propofol in both groups to maintain BIS between 40 and 50, we suggested that the sufentanil-propofol synergism is greater than the remifentanil-propofol.

3. Regarding recovery, we are in agreement that the correct description would be "de facto" analgesia caused by sufentanil, since the concept of residual analgesia is related with concentrations below 0.05 ng.dL

   ^-1. However, this does not change the fact that, in our study, patients in the sufentanil group had decreased postoperative pain and, therefore, the length of stay in the recovery room was smaller than in the remifentanil group.

Dr. Ricardo Francisco Simoni

REFERENCES

• 01. Gepts E, Jonckheer K, Maes V et al. - Disposition kinetics of propofol during alfentanil anaesthesia. Anaesthesia, 1988;43: 8-13.
• 02. Glass PSA, Shafer SL, Reves JG - Intravenous Drug Delivery Systems, em: Miller RD - Miller´s Anesthesia, 6^th Ed, Philadelphia, Elsevier, 2005;439-480.
• 03. Vuyk J, Mertens MJ, Oolofsen E et al. - Proposal anesthesia and rational opioid selection: determination of optimal EC50-EC95 propofol-opioid concentrations that assure adequate anesthesia and a rapid return of consciousness. Anesthesiology, 1997; 87:1549-1562.
• 04. Shafer SL, Schiwinn DA - Basic Principles of Pharmacology Related to Anesthesia, em: Miller RD - Miller´s Anesthesia, 6^th Ed, Philadelphia, Elsevier, 2005;67-104.
• 05. www.eurosiva.org/tivatrainer
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Publication Dates

• Publication in this collection
  04 Sept 2008
• Date of issue
  Oct 2008