The Comparative Risk of Delirium with Different Opioids: A Systematic Review

Drugs Aging. 2017 Jun;34(6):437-443. doi: 10.1007/s40266-017-0455-9.


Objective: There is substantial evidence that the use of opioids increases the risk of adverse outcomes such as delirium, but whether this risk differs between the various opioids remains controversial. In this systematic review, we evaluate and discuss possible differences in the risk of delirium from the use of various types of opioids in older patients.

Methods: We performed a search in MEDLINE by combining search terms on delirium and opioids. A specific search filter for use in geriatric medicine was used. Quality was scored according to the quality assessment for cohort studies of the Dutch Cochrane Institute.

Results: Six studies were included, all performed in surgical departments and all observational. No study was rated high quality, one was rated moderate quality, and five were rated low quality. Information about dose, route, and timing of administration of the opioid was frequently missing. Pain and other important risk factors of delirium were often not taken into account. Use of tramadol or meperidine was associated with an increased risk of delirium, whereas the use of morphine, fentanyl, oxycodone, and codeine were not, when compared with no opioid. Meperidine was also associated with an increased risk of delirium compared with other opioids, whereas tramadol was not. The risk of delirium appeared to be lower with hydromorphone or fentanyl, compared with other opioids. Numbers used for comparisons were small.

Conclusion: Some data suggest that meperidine may lead to a higher perioperative risk for delirium; however, high-quality studies that compare different opioids are lacking. Further comparative research is needed.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Aged
  • Analgesics, Opioid / adverse effects*
  • Analgesics, Opioid / therapeutic use
  • Delirium / chemically induced*
  • Humans
  • Hydromorphone / adverse effects
  • Hydromorphone / therapeutic use
  • Meperidine / adverse effects
  • Meperidine / therapeutic use
  • Morphine / adverse effects
  • Morphine / therapeutic use
  • Oxycodone / adverse effects
  • Oxycodone / therapeutic use
  • Pain / drug therapy*
  • Pain Measurement / methods*
  • Risk Factors
  • Tramadol / adverse effects
  • Tramadol / therapeutic use


  • Analgesics, Opioid
  • Tramadol
  • Morphine
  • Meperidine
  • Oxycodone
  • Hydromorphone