The major adverse reactions associated with fentanyl are respiratory depression, apnea, muscle rigidity, myoclonic movements and bradycardia, which if untreated, can lead to conditions such as cardiac arrest, circulatory depression and respiratory arrest.
Respiratory depression (usually associated with intravenous use) can be immediately reversed by an opioid antagonist. The respiratory depression is more likely to occur if the intravenous injection is given too rapidly; it rarely occurs with intramuscular injection. Secondary rebound respiratory depression has been observed after the operation in rare instances.
Muscle rigidity is a common side effect, and may be associated with reduced pulmonary compliance and/or apnea, laryngospasm or bronchospasm. It may be reversed by intravenous administration of a muscle relaxant such as suxamethonium followed by controlled or artificial respiration.
Bradycardia can be controlled by the use of atropine. Bradycardia and other cholinergic effects are less likely if atropine or other anticholinergic agents are included in the pre-anesthetic regimen.
Other reported adverse effects of fentanyl, when used alone, include elevated blood pressure, hypotension, blurred vision, dizziness, nausea, emesis, laryngospasm, diaphoresis, itching, euphoria and spasm of the sphincter of Oddi.
Less frequently, cardiac arrhythmias, postoperative mental depression, paradoxical CNS excitation or delirium may occur. Motor stimulation and bronchospasm may occur with high doses of fentanyl. Miosis or seizures may occur.
When used in conjunction with a neuroleptic agent such as droperidol, reported adverse effects include chills and/or shivering, restlessness, post operative hallucinations, drowsiness, mental depression and extrapyramidal symptoms (dystonia, akathisia and oculogyric crisis). These have been observed up to 24 hours postoperatively. Elevated blood pressure, with or without pre-existing hypertension, has been reported following administration of fentanyl combined with droperidol. This might be due to unexplained alterations in sympathetic activity following large doses; however, it is also frequently attributed to anesthetic and surgical stimulation during light anesthesia.
Allergic reactions (such as anaphylaxis, bronchospasm, pruritis, urticaria) and asystole have been reported following the co-administration of several drugs during anesthesia. However, it is uncertain whether these reactions have a causal relationship with fentanyl.