This risk is higher in specific groups, like those with obstructive sleep apnea.Other factors that increase the risk of respiratory depression are:
High fentanyl doses
Sleep
Older age
Simultaneous use of CNS depressants like benzodiazepines, barbiturates, alcohol, and inhaled anesthetics
Hyperventilation
Decreased CO2 levels in the serum
Respiratory acidosis
Decreased fentanyl clearance from the body
Decreased blood flow to the liver
Renal insufficiencySustained release fentanyl preparations, such as patches, may also produce unexpected delayed respiratory depression. 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 causing cutaneous vasodilation (releasing more fentanyl), together with acidosis, which reduces 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 section below. Heart and blood vessels
Bradycardia: Fentanyl decreases the heart rate by increasing vagal nerve tone in the brainstem, which increases the parasympathetic drive. Vasodilation: It also vasodilates arterial and venous blood vessels through a central mechanism, by primarily slowing down vasomotor centers in the brainstem. To a lesser extent, it does this by directly affecting blood vessels.
Quantitative measurement of amino acids in plasma and urine
IEX-Ninhydrin post-column derivitization liquid ion chromatography (detects abnormal amino acid patterns and quantitative analysis)
Urine organic acid analysis by gas chromatography–mass spectrometry
Plasma acylcarnitine analysis by mass spectrometry
Urine purine and pyrimidine analysis by gas chromatography-mass spectrometrySpecific diagnostic tests (or focused screening for a small set of disorders):

Tissue biopsy: liver, muscle, brain, bone marrow
Skin biopsy and fibroblast cultivation for specific enzyme testing
Specific DNA testingA 2015 review reported that even with all these diagnostic tests, there are cases when "biochemical testing, gene sequencing, and enzymatic testing can neither confirm nor rule out an IEM, resulting in the need to rely on the patients clinical course". A 2021 review showed that several neurometabolic disorders converge on common neurochemical mechanisms that interfere with biological mechanisms also considered central in ADHD pathophysiology and treatment. This highlights the importance of close collaboration between health services to avoid clinical overshadowing. Treatment
In the middle of the 20th century the principal treatment for some of the amino acid disorders was restriction of dietary protein and all other care was simply management of complications. In the past twenty years, new medications, enzyme replacement, gene therapy, and organ transplantation have become available and beneficial for many previously untreatable disorders. Some of the more common or promising therapies are listed:

Epidemiology
In a study in British Columbia, the overall incidence of the inborn errors of metabolism were estimated to be 40 per 100,000 live births or 1 in 2,500 births, overall representing more than approximately 15% of single gene disorders in the population.