Nigerian Journal of Clinical Practice

: 2017  |  Volume : 20  |  Issue : 1  |  Page : 119--122

Immediate resolution of acute, choreatic hyperkinesias following intravenous fentanyl

J Finsterer, J Rettensteiner 
 Krankenanstalt Rudolfstiftung, Vienna, Austria

Correspondence Address:
Dr. J Finsterer
Krankenanstalt Rudolfstiftung, Postfach 20, 1180 Vienna


Acute hyperkinesia after discontinuation of tramadol in a patient with chronic pain using citalopram and pramipexole for restless legs syndrome (RLS) has not been reported. An 81-year-old female was admitted for increasing hyperkinesias of the whole body after she had discontinued tramadol 300 mg (taken during 3 months) without tapering 4 days earlier. In addition, she was on treatment with pramipexole (0.18 mg) for RLS for years, citalopram 10 mg/day for ~4 years, and fentanyl 75 μg/day for 1 year. Hyperkinesias did not respond to benzodiazepines, quetiapine, biperiden, or valproic acid. Surprisingly, hyperkinetic bursts resolved immediately upon 15 mg fentanyl intravenously. Obviously, tramadol withdrawal had enhanced the preexisting RLS. Overdosing of pramipexole or serotonin syndrome was excluded. Sudden discontinuation of tramadol in a patient under pramipexole for RLS may cause severe, choreatic hyperkinesias for hours, which immediately resolve upon intravenous fentanyl. In patients under pramipexole for RLS and tramadol and fentanyl for chronic pain, sudden discontinuation of tramadol should be avoided to prevent induction of restless body syndrome.

How to cite this article:
Finsterer J, Rettensteiner J. Immediate resolution of acute, choreatic hyperkinesias following intravenous fentanyl.Niger J Clin Pract 2017;20:119-122

How to cite this URL:
Finsterer J, Rettensteiner J. Immediate resolution of acute, choreatic hyperkinesias following intravenous fentanyl. Niger J Clin Pract [serial online] 2017 [cited 2019 Dec 13 ];20:119-122
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Full Text


Acute drug-associated hyperkinesias are rare [1] and have not been reported in association with opiate treatment and restless leg syndrome (RLS). Here, we present a patient under citalopram, fentanyl, and pramipexole for RLS who developed severe hyperkinesias after immediate discontinuation of tramadol.

 Case Report

The patient is an 81-year-old nonsmoking, HIV-negative, Caucasian female, height 165 cm, weight 66 kg, who was admitted in June 2015 because of acute-onset recurrent bursts of hyperkinesias affecting the lower and upper limbs, trunk, and head since 8.00 pm. On admission at 10.00 pm, she was alert, adequately reacting, and was able to walk unaided. She denied headache, vertigo, exsiccosis, intake of illicit drugs, previous journey to the tropics, coughing, close contact with animals, tuberculosis, fever, or diarrhea. Her previous history is listed in [Table 1]. She was on a permanent medication with acetyl-salicylic acid (100 mg/d), L-thyroxin (100 mg/d), pantoprazole (40 mg/d), bisoprolol (1.25 mg/d), valsartan (20 mg/d), furosemide (30 mg/d) since 2 years, citalopram (10 mg/d), pramipexole (0.18 mg/d) since years with interruptions but regularly again since 1.5 years, transdermal fentanyl (75 mg/d) since 1 year, budesonide plus formoterol (540 mg/d), and tiotropium-bromide (18 mg/d). Four days before admission, she herself had discontinued tramadol (300 mg/day) because of hyperhidrosis, which replaced diclofenac she had been taken during years until 3/2015. On demand, she also took paracetamol (500–1000 mg/day).{Table 1}

To stop progressing hyperkinesias, she initially received diazepam (10 mg), and because of ineffectivity, consecutively, she received quetiapine (25 mg), lorazepam (4 mg), and diazepam (20 mg), all without a beneficial effect. At 3.00 am on hospital day (hd) 2, she was first referred to the neurologist who found a somnolent patient inconsistently following his requests and presenting with severe choroid hyperkinetic movements, which followed a recurrent pattern of involuntary leg and arm movements followed by pushing up to a sitting posture and rotatory motions involving the head. Hyperkinetic bursts were interrupted by episodes of relative rest for a few seconds. Biperiden (10 mg) resulted in slight reduction of the intensity of hyperkinesias and induced sleep with snoring. Urine bladder catheterization and release of 500 ml urine were ineffective. Valproic acid (400 mg) intravenously did not reduce hyperkinesias either. Except for somnolence and impaired hearing, neurologic examination was normal.

To exclude the central nervous system (CNS) disorder, cerebral computed tomography (CT) with contrast medium under general anesthesia was carried out. After she had received fentanyl intravenously (15 mg) as a premedication, surprisingly, hyperkinesias immediately and permanently stopped. Nonetheless, she received propofol (80 mg) followed by rocuronium (50 mg) and was intubated. Cerebral CT showed leukoaraiosis and precluded ischemia, bleeding, tumor, or edema. Large cerebral arteries and veins were patent. Lumbar puncture only showed positive oligoclonal bands. Blood tests showed mild anemia, mild renal insufficiency, and mild hyponatremia [Table 2]. Creatine kinase, thyroid function, and procalcitonin were normal. β-microglobulin was 2.3 mg/L (n, 0.8–2.2 mg/L). Screening for intoxication with ethanol, barbiturates, benzodiazepines, and tricyclic antidepressants was negative. Flumazenil was not administered as seizures could not definitively be excluded. After extubation at 9.00 am on hd-2, hyperkinesias did not recur. Electroencephalography at 11.00 am on hd-2 did not show paroxysmal activity. Cerebral magnetic resonance imaging on hd-5 showed periventricular leukoaraiosis, pontine gliosis, and lipomatosis of the cerebellar vermis. The patient consented with publication of his case.{Table 2}


The presented patient is interesting for immediate resolution of severe, generalized, periodic choroid hyperkinesias by intravenous fentanyl, which had started 9 h earlier and increased over time. Several speculations can be raised to explain hyperkinesias: Overdosing, side effect, or withdrawal of a drug, intoxication, paraneoplastic syndrome, relapse of lymphoma, vascular impairment, meningitis/encephalitis, immune-mediated condition, metabolic impairment, polypharmacy, or genetic disease [Table 3]. Most of these differentials were excluded by history, clinical examination, instrumental investigations, and the effect of fentanyl [Table 3].{Table 3}

Remaining explanations for hyperkinesias were overdosing of pramipexole, serotonin syndrome (SS), opiate withdrawal, or genetic defect. Overdosing of pramipexole is unlikely since the dosage was low and constant, since metabolization of pramipexole was not impaired, and since fentanyl was effective. Furthermore, pramipexole has been reported to reduce but not to increase L-DOPA-induced dyskinesia.[2] SS was excluded upon the absence of tremor, seizures, dizziness, insomnia, headache, hyperreflexia, arterial hypertension, ocular clonus, or whole body pain.[3] Further, arguments against SS are that hyperkinesias are not a manifestation of SS [3] and that citalopram was taken since years at a constant dosage. Since Hunter's criteria (Hunter serotonin toxicity criteria) or Sternbach's criteria for diagnosing SS were not accomplished, cyproheptadine, the treatment of choice for SS, was not administered.[3] Whether there was an underlying genetic defect which manifested as multi-organ disorder syndrome (MODS) remains speculative. Arguments in favor of an underlying mitochondrial MODS (MIMODS) are the short stature, impaired hearing, cataract, hypothyroidism, diverticulosis, renal insufficiency, arterial hypertension, hyperlipidemia, double kidney, muscle cramps, and polyneuropathy. Lymphoma may be part of MIMODS as well since the prevalence of malignancies is increased in MIMODS.[4] Further, diagnostic work-up into this direction was refused by the patient.

The impressive beneficial effect of fentanyl suggested that opiate deficiency or insensitivity of opiate receptors was responsible for hyperkinesias. The cause of opiate deficiency, however, remains speculative. One explanation could be reduced provision of the drug, but the patient denied having forgotten to fix the transdermal patch. It is also conceivable that resorption of fentanyl via the skin had decreased due to the co-medication or metabolic factors. Nonetheless, discontinuation of tramadol 4 days before onset of hyperkinesias was the most likely cause. Possibly, tramadol withdrawal enhanced the preexisting RLS. From animal studies, it is known that opiates sensitize dopamine receptors.[5] In addition, it is known that dopamine receptor antagonists decrease opiate tolerance.[6] In addition, pramipexole has a beneficial effect on restlessness caused by opiate withdrawal.[7] It is also conceivable that one of the drugs or its combination displaced fentanyl from opiate receptors. Arguments against drug interaction, however, are that they were taken since years and that except for tramadol, the dosage of those affecting the CNS, was low and constant. Another explanation for opiate deficiency could be increased demand of the drug due to upregulation of the number of opiate receptors or tachyphylaxia. However, there was no evidence for increased excretion (diuretic, renal insufficiency) or increased liver metabolism of opiates. She had not received naloxone before admission.


This case shows that discontinuation of tramadol in a patient under pramipexole for RLS may cause severe choroid hyperkinesias over hours, which immediately resolve upon intravenous fentanyl. In patients with RLS treated with pramipexole and chronic pain treated with tramadol and fentanyl, sudden discontinuation of tramadol should be avoided to prevent triggering of restless body syndrome.

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