title: Withdrawal following sufentanil/propofol and sufentanil/midazolam. Sedation in surgical ICU patients: correlation with central nervous parameters and endogenous opioids.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, County Hospital Klagenfurt, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Korak-Leiter
authors.forename: Rudolf
authors.initials: R
authors.lastname: Likar
authors.forename: Michael
authors.initials: M
authors.lastname: Oher
authors.forename: Ernst
authors.initials: E
authors.lastname: Trampitsch
authors.forename: Gerda
authors.initials: G
authors.lastname: Ziervogel
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Levy
authors.forename: Enno C
authors.initials: EC
authors.lastname: Freye
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D016292:Procedural Sedation / Q000009:adverse effects*; D003422:Critical Care / Q000379:methods; D003693:Delirium / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004569:Electroencephalography; D004744:Enkephalin, Methionine / Q000097:blood / Q000187:drug effects; D005073:Evoked Potentials, Somatosensory; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D008297:Male; D008874:Midazolam / Q000009:adverse effects*; D008875:Middle Aged; D011182:Postoperative Care / Q000009:adverse effects; D015742:Propofol / Q000009:adverse effects*; D013375:Substance Withdrawal Syndrome; D017409:Sufentanil / Q000009:adverse effects*; D001615:beta-Endorphin / Q000097:blood / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D004744:Enkephalin, Methionine; D001615:beta-Endorphin; D017409:Sufentanil; D008874:Midazolam; D015742:Propofol