Adverse effects of opioid analgesic treatment are correlated with a significant elevation in plasma epinephrine in healthy humans

Abstract

Objective: The purpose of this study was to elucidate the relationship of plasma catecholamine concentrations with experienced pain intensity and analgesic effects in the setting of an experimental pain study with human volunteers.

Methods: Plasma norepinephrine and epinephrine concentrations of 12 healthy human volunteers were analysed before and during painful electrical tooth-pulp stimulation under medication using the highly potent opioid analgesic tilidine in a fixed tilidine/naloxone combination and with the non-steroidal anti-inflammatory agent bromfenac. Catecholamine levels were compared with pharmacodynamic effects and reported adverse effects.

Results: Catecholamine levels revealed a statistically significant increase in plasma epinephrine concentrations (but not norepinephrine concentrations) 60–90 min after administration of tilidine/naloxone. This was correlated with the onset of adverse effects involving vertigo episodes in all reported cases. In contrast, there was no obvious correspondence of epinephrine or norepinephrine plasma concentrations to the experience of pain and analgesia. For comparison, under medication with the non-opioid analgesic bromfenac, only one mild adverse effects were noted, and no changes in plasma epinephrine or norepinephrine could be determined during the experimental sessions.

Conclusions: It is proposed that elevated plasma epinephrine concentrations are a newly determined response to opioid-induced vertigo; this has possible clinical implications.