Vasovagal reactions following venepuncture result in aberrant stress-induced cortisol levels

Venepuncture is recognized as a potent stressor and, by activating the hypothalamic-pituitary-adrenal (HPA) axis, can interfere with measuring subsequent HPA axis indices such as cortisol. A resting period of 110 min is recommended between venepuncture and the commencement of psychosocial stress induction or cortisol measurement to allow cortisol levels to return to baseline first. In experiment 1 (n = 65), in which stress induction occurred 120 min after venepuncture, we observed three cortisol stress response patterns: conventional response ("responders", 77%), conventional non-response ("non-responders", 6.15%), and aberrant non-response characterized by high baseline (pre-stress) cortisol levels ("high-baseliners", 16.9%). Based on subjective clinical observation, the aberrant non-response was exclusively present in those who experienced vasovagal reactions during venepuncture, ranging from nervousness, lightheadedness, nausea, feeling of being extremely hot or cold, confusion, slight inability to speak, weakness and visual disturbances, to loss of consciousness (syncope). In experiment 2 (n = 79), we showed that allowing 210 min between venepuncture and stress induction permits the return of cortisol levels back to baseline even in participants who experience vasovagal reactions, thereby allowing for the exhibition of a conventional cortisol stress response. In sum, while 110 min may be sufficient to circumvent the usual effects of venepuncture on cortisol levels, 210 min are needed to effectively adjust for the effects of venepuncture-induced vasovagal reactions and the subsequent sustained rise in cortisol. Allowing sufficient time between venepuncture and stress induction or cortisol measurement should also prevent misclassification of participants who show aberrant responses as non-responders or anticipatory responders.