ABSTRACT
PURPOSE: Patients in the ICU after long-term administration of an opioid/hypnotic often develop delirium. To assess the nature of this phenomenon, patients in a surgical ICU following ventilatory support and sedation with an opioid/hypnotic/sedative were studied. METHODOLOGY: Following sufentanil/midazolam (group 1; n =14) or sufentanil/propofol (group 2; n =15) sedation, patients were evaluated for changes in mean arterial blood pressure and heart rate, the activity of the central nervous system (sensory evoked potentials, spectral edge frequency of EEG), and the endogenous opioids plasma concentrations (beta-endorphin, met-enkephalin). Data obtained were correlated with the individual intensities of withdrawal symptoms 6-, 12-, and 24 h following sedation. RESULTS: Following a mean duration of ventilation of 7.7 days (+/-3.6 SD) in groups 1 and 3.5 (+/-1.7 SD) in group 2, withdrawal intensities peaked within the 6th hour after cessation. Plasma beta-endorphin and met-enkephalin levels were low during sedation, and only the sufentanil/midazolam group demonstrated a postinhibitory overshoot. Withdrawal symptom intensities demonstrated an inverse correlation with beta-endorphin and met-enkephalin levels, a direct linear correlation with amplitude height of the evoked potential, and blood pressure and heart rate changes. Withdrawal intensities did not correlate with EEG power spectral edge frequency. CONCLUSION: The endorphinergic system is suppressed when a potent exogenous opioid like sufentanil is given over a long period of time. Following sedation, abstinence symptoms seem to be related to postinhibitory increased endorphin synthesis. This is mostly seen in the combination of sufentanil/midazolam. In addition, an increase in the amplitude of the sensory-evoked potential suggests a postinhibitory excitatory state within the nociceptive system.
