Effect site concentrations of remifentanil and pupil response to noxious stimulation

Background. Opioid drugs block reflex pupillary dilatation in response to noxious stimulation. The relationship between the target effect site concentration (Ce-T) of remifentanil and the pupil diameter and reactivity in response to a standard noxious stimulus were evaluated. Methods. Anaesthesia was induced with propofol TCI to obtain loss of consciousness (LOC) in 12 ASA I/II patients. Thereafter, remifentanil Ce-T was titrated by increments of 1 up to 5 ng ml(-1). In the awake state, at LOC and at each plateau level of remifentanil Ce-T, arterial pressure, heart rate, and BIS (A2000) were recorded. Pupil size and dilatation after a 100 Hz tetanic stimulation (T100) were measured at LOC and at each plateau level of remifentanil Ce-T. Results. LOC was observed at a mean propofol Ce-T of 3.53 (sd 0.43) mug ml(-1). Arterial pressure and heart rate decreased progressively from LOC to 5 ng ml(-1) remifentanil Ce-T without any statistical difference between each incremental dose of remifentanil. Mean BIS values decreased from 96 (2) in the awake state, to 46 (12) at LOC (P<0.05) and then remained unchanged at all remifentanil Ce-T. Pupil dilatation in response to 100 Hz tetanic stimulation decreased progressively from 1.55 (0.72) to 0.01 (0.03) mm and was more sensitive than pupil diameter measured before and after 100 Hz tetanus. An inverse correlation between pupil dilatation in response to 100 Hz tetanus and an increase in remifentanil Ce-T from 0 to 5 ng ml(-1) was found (R-2=0.68). Conclusions. During propofol TCI in healthy patients, the decrease in pupil response to a painful stimulus is a better measurement of the progressive increase of remifentanil Ce-T up to 5 ng ml(-1) than haemodynamic or BIS measurements.