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Complications

The use of opioids in renal failure

Renal failure can cause significant and dangerous side‐effects due to the accumulation of opioids. A systematic review in patients with cancer pain concluded that fentanyl, alfentanil and methadone, with caveats, are the medications likely to cause least harm in patients with renal impairment when used appropriately (King et al. [88]). Basic guidelines for pain management in renal failure include the following:

reduce analgesia dose and/or dose frequency (6‐hourly instead of 4‐hourly)
select a more appropriate drug (not renally excreted)
avoid modified‐release preparations
seek advice from a specialist pain or palliative care team and/or pharmacist (Farrell and Rich [55]).

Endocrine system

Long‐term administration of opioids is associated with endocrine abnormalities (FPM [59]):

Influences on both the hypothalamic–pituitary–adrenal axis and the hypothalamic–pituitary–gonadal axis have been demonstrated in patients taking oral opioids, with consequent hypogonadism and adrenal insufficiency in both sexes.
Hypogonadism and decreased levels of dehydroepiandrosterone sulphate have been reported in men and women.

Immune system

Opioids have also been shown to affect the immune system (FPM [59]):

Both animal and human studies have demonstrated that opioids have an immunomodulating effect. These effects are mediated via opioid receptors both on immune effector cells and in the central nervous system.
In animals, opioids have been demonstrated to have effects on antimicrobial response and anti‐tumour surveillance. Opioids may differ in their propensity to cause immunosuppression.
In animal studies, buprenorphine has been demonstrated to have no impact on immune function. The relevance of these findings to the clinical use of opioids is not known.

Fractures and falls

Opioids have a number of implications for the risk of fractures and falls (FPM [59]):

Opioids increase the risk and incidence of falls. This is of particular importance in elderly patients.
In a systematic review of observational studies, the relative risk of any fracture in patients on opioids compared to non‐using patients was 1.38.
The relative risk of falls associated with opioids was similar to the risks associated with benzodiazepines (1.34 compared to non‐using patients) and antidepressants (1.60 compared to non‐using patients).

Opioid‐induced hyperalgesia

Finally, opioids can have implications for pain sensitivity (FPM [59]):

Both animal and human studies have demonstrated that prolonged use of opioids can lead to a state of abnormal pain sensitivity sometimes called opioid‐induced hyperalgesia (OIH).
The prevalence of OIH in clinical practice is unknown.