Article Text

Acute adverse reaction to fentanyl in a 55 year old man
  1. Neurological Department, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
  1. Dr HJ Stuerenburg stuerenburg{at}

Statistics from

We report an acute drug induced adverse reaction to fentanyl that was not immediately recognised as such. A 55 year old police officer was given a small dose of diazepam (5 mg) and fentanyl (0.05 mg) for the treatment of left chest pain. Immediately after receiving the medication, the patient developed acute confusion, intermittent somnolence, and stupor, and fluctuating tetraparesis. Before the onset of symptoms, no relevant hypoxia or hypoglycaemia were found. Pre-existing medication consisted of 20 mg amitryptiline and 1000 mg metformin a day. On initial examination, the most obvious symptoms included profuse sweating, bilateral miosis (pinpoint pupils), and severe generalised myoclonus predominantly affecting the face. Babinski‘s sign was negative on both sides. The patient showed severe fluctuating tetraparesis. Investigation of the cranial nerves showed no abnormalities. On admission in our institution, the patient immediately underwent intubation and artificial ventilation for suspected pulmonary aspiration. Thiamin was started at 100 mg thrice daily. Myocardial infarction and dissection of the aorta were ruled out. The previously given dosage of fentanyl and diazepam did not seem to explain the current neurological condition of the patient. The symptoms of disturbance of conciousness, hemiparesis, generalised myoclonus, and pinpoint pupils pointed to brainstem injury. To rule out basilar artery thrombosis, CT angiography was performed. There were no pathological findings in the brainstem or the basilar artery.

Transcranial Doppler ultrasound and sensory evoked potentials were normal. The EEG under sedation with midazolam and fentanyl showed intermittent bilateral synchronised frontal delta rhythms. Systolic blood pressure was slightly increased, between 140 and 180 mm Hg. Due to the patient‘s development of pneumonia, artificial ventilation was continued, and further sedation was given with fentanyl/midazolam. Sedation was continued for 72 hours, with an infusion of fentanyl (0.157 mg/h) and midazolam (3.3 mg/h) for ventilation therapy. After sedation was stopped, the distinctive neurological symptoms abruptly improved. Within a few hours the patient was extubated. He then seemed normal, except for slight disorientation and agitation. Twelve hours after cessation of sedation, the patient was normal. To clarify and confirm the diagnosis of an adverse reaction to fentanyl, we carried out a provocation test after obtaining full informed consent. A dose of 0.1 mg fentanyl intravenously was enough to induce agitation, generalised myoclonus, and paroxysmal dystonic movements and rigor that particularly affected the legs. No cognitive disturbances were apparent. The fentanyl dose was then increased to a total of 0.2 mg. At this point, a 6 mg dose of diazepam was given but did not improve the agitation of the patient. In fact the patient reported increased agitation. Administration of a morphine antagonist, naloxone (0.8 mg intravenously) dramatically improved his condition, completely normalising the myoclonus, rigor, and paroxysmal movements. No further improvement occurred on administration of the benzodiazepine antagonist flumazenil (0.25 mg intravenously). As the effect of the naloxone wore off, there was a reappearance of the dystonic movements. Under these conditions, the patient presented with distinct bilateral miosis, but no other disturbances.

Through this provocation test, the diagnosis was confirmed. As a result of an adverse reaction to fentanyl, the patient experienced an acute and unusual neurological syndrome. The clinical symptoms were agitation, generalised myoclonus, intermittent disturbances of consciousness, fluctuating bilateral hemiparesis, and pinpoint pupils. The diagnosis remained obscure for 72 hours due to the continuing ventilation, sedation, and analgesic treatment with fentanyl; indeed, it was the continuing administration of fentanyl that was maintaining the symptoms. Both the improvement after cessation of fentanyl, and the controlled provocation test confirmed the diagnosis.

In recent years, various central side effects of opioids have been described. These include generalised myoclonus, hyperalgesia, grand mal seizures, and agitation.1-4 Although some reports have shown unexpected cerebral side effects after low doses of fentanyl,5 in most cases this type of effect developed in patients receiving high doses of opiates for prolonged periods.1-3

Opiate induced myoclonus is often generalised and is either periodic or associated with rigidity, often occurs in the context of underlying medical conditions, and usually responds to either naloxone or benzodiazepines.4 The mechanisms responsible for these adverse effects are not exactly known, but opiatergic, serotonergic, dopaminergic, and other mechanisms are considered.4 The interesting feature of this particular case was the possibility of confusion of an acute fentanyl induced adverse syndrome with basilar artery thrombosis.


View Abstract

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.