Editing Fentanyl (section)

=== Respiratory depression ===
The most dangerous adverse effect of fentanyl is respiratory depression,<ref>{{cite journal |vauthors = Topacoglu H, Karcioglu O, Cimrin AH, Arnold J |title = Respiratory arrest after low-dose fentanyl |journal = Annals of Saudi Medicine |volume = 25 |issue = 6 |pages = 508–510 |date = Nov 2005 |pmid = 16438465 |pmc = 6089740 |doi = 10.5144/0256-4947.2005.508}}</ref> that is, decreased sensitivity to carbon dioxide leading to reduced rate of breathing, which can cause anoxic brain injury or death. This risk is decreased when the airway is secured with an [[endotracheal tube]] (as during anesthesia).<ref name="Hemmings_2018" /> This risk is higher in specific groups, like those with [[obstructive sleep apnea]].<ref name="Hemmings_2018" />

Other factors that increase the risk of respiratory depression are:<ref name="Hemmings_2018" />
* High fentanyl doses
* Simultaneous use of [[methadone]]
* Sleep
* Older age
* Simultaneous use of CNS depressants like benzodiazepines (i.e. [[alprazolam]], [[diazepam]], [[clonazepam]]), barbiturates, alcohol, and inhaled anesthetics
* Hyperventilation
* Decreased CO<sub>2</sub> levels in the serum
* Respiratory [[acidosis]]
* Decreased fentanyl clearance from the body
* Decreased blood flow to the liver
* Renal insufficiency

Sustained release fentanyl preparations, such as patches, may also produce unexpected delayed [[respiratory depression]].<ref name="pmid9472602">{{cite journal |vauthors = McLoughlin R, McQuillan R |title = Transdermal fentanyl and respiratory depression |journal = Palliative Medicine |volume = 11 |issue = 5 |page = 419 | date = September 1997 |pmid = 9472602 |doi = 10.1177/026921639701100515 }}</ref><ref name="pmid7484044">{{cite journal |vauthors = Bülow HH, Linnemann M, Berg H, Lang-Jensen T, LaCour S, Jonsson T |title = Respiratory changes during treatment of postoperative pain with high dose transdermal fentanyl |journal = Acta Anaesthesiologica Scandinavica |volume = 39 |issue = 6 |pages = 835–839 |date = August 1995 |pmid = 7484044 |doi = 10.1111/j.1399-6576.1995.tb04180.x |s2cid = 22781991 }}</ref><ref name="pmid14694924">{{cite journal |vauthors = Regnard C, Pelham A |title = Severe respiratory depression and sedation with transdermal fentanyl: four case studies |journal = Palliative Medicine |volume = 17 |issue = 8 | pages = 714–716 |date = December 2003 |pmid = 14694924 |doi = 10.1191/0269216303pm838cr |s2cid = 32985050 }}</ref> The precise reason for sudden respiratory depression is unclear, but there are several hypotheses:
* Saturation of the body fat compartment in people with rapid and profound body fat loss (people with cancer, cardiac or infection-induced [[cachexia]] can lose 80% of their body fat).
* Early carbon dioxide retention causes cutaneous vasodilation (releasing more fentanyl), together with acidosis, which reduces the protein binding of fentanyl, releasing yet more fentanyl.
* Reduced sedation, losing a useful early warning sign of opioid toxicity and resulting in levels closer to respiratory-depressant levels.

Another related complication of fentanyl overdoses includes the so-called [[wooden chest syndrome]], which quickly induces complete respiratory failure by paralyzing the thoracic muscles, explained in more detail in the [[#Muscle rigidity|Muscle rigidity section]] below.