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Re: Propofol tolerance - young male
- Harald Ihmsen (5 October 2007)
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Propofol tolerance - young male
- jithesh appukutty (28 September 2007)
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Harald Ihmsen Department of Anaesthesiology, University of Erlangen, Germany
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It is interesting that the article reported the development of acute tolerance in man within a relatively short time of two hours. In man, tolerance is usually observed after long-term administration over some days, whereas we observed in rats development of tolerance also within one to two hours.(1) Although the observation seems to confirm in part our results in rats, one must be careful. The main problem with this case report is the missing information about the actual propofol concentrations. In the rat study, we observed a constant anaesthetic effect (measured by the EEG) with increasing measured plasma concentrations, whereas in the present case report there is only the information that the propofol dose was increased to maintain a defined level of anaesthesia. Therefore one cannot decide whether this was caused by changed pharmacokinetics (e.g. change in clearance) or by changed pharmacodynamics, and only an alteration in pharmacodynamics would be called „tolerance“. Thus one should rather call the presented observation „apparent tolerance“. The combination of various drugs (midazolam, fentanyl and propofol) and the combination of bolus dose and continuous infusion for propofol makes it also difficult to conclude that tolerance to propofol occurred. During the first 30 min, the concentrations of midazolam, fentanyl and also propofol decreased continuously, as one can easily see by doing a simulation. Therefore, it is more likely that the concentrations were in the therapeutic range at the beginning but subsequently fell below the lower limit of the therapeutic range, so that they were inadequate at 30 min. Subsequently, the infusion rate was increased to achieve an appropriate concentration. However, as it needs some time, until the plasma concentration has achieved a new steady state when only the infusion rate is increased (and the effect site concentration needs still more time!), additional bolus doses were necessary. Besides, in this case, a target controlled infusion would have been useful as it gives a bolus dose and increases the infusion rate if the target is increased, so that the higher concentration is achieved faster. In conclusion, I would be careful to call the presented observation an indication that development of tolerance really occurred. (1) Ihmsen H et al. Development of acute tolerance to the EEG effect of propofol in rats. Br J Anaesth 2005; 95: 367-371 Conflict of Interest:None declared |
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jithesh appukutty
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Tolerance to propofol usually develops during long-term administration in critically ill adult(1)or pediatric patients during mechanical ventilation(2) We report a case which developed acute tolerance to propofol infusion. A 30 year old male with no significant illness weighing 60 kg was given brachial plexus block - axillary approach for right ulnar implant removal. Post plexus block the patient was given Inj Midazolam 3mg i.v., Inj fentanyl 200 mcg i.v., and a loading of propofol 60 mg was given followed by propofol infusion 50mcg/kg/min. Half hour later the dose had been stepped up to 100mcg/kg/min as the patient started to move and open eyes. The patient required frequent boluses of propofol 50 mg every 15 min the keep in immobile state. Towards the end of surgery nearly two hours after start of surgery the infusion rate was stepped down to 50 mcg/kg/min. The patient became fully conscious within 5 minutes of stepping down and was vocalising normally with 50mcg/kg/min of propofol infusion. The patient had an uneventful postoperative period. pharmacokinetic tolerance to propofol’s sedative effect develops within the first 1–2 hours in mechanically ventilated rabbits.(3)In our patient the same seems to develop around one hour, suggested by the increase in requirement of propofol. Eventhough tolerance to propofol is a rare entity one has to be on the look out for patients who require progressive increase in propofol requirement. References: 1.Buckley PM. Propofol in patients needing long-term sedation in intensive care: an assessment of the development of tolerance: a pilot study. Intensive Care Med 1997;23:969–74 2.Bray RJ. Propofol infusion syndrome in children. Paediatr Anaesth 1998;8:491–9 3.Ypsilantis P et al. Tolerance to Propofol’s Sedative Effect in Mechanically Ventilated Rabbits. Anesth Analg 2006;103:359-365 Conflict of Interest:None declared |
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