Fentanyl-induced encephalopathy

Introduction Fentanyl is a synthetic opioid drug that is extensively used for analgesia and sedation. Its rapid onset and brief duration make it especially beneficial for pain management and sedation in critically ill patients who need mechanical ventilation or other invasive procedures. While the administration of fentanyl in the ICU is generally considered safe, there are occasions where it can lead to notable adverse effects. Here, we describe a unique case of encephalopathy associated with fentanyl use. Case presentation A 62-year-old, thin-built male patient presented to the emergency room with a chief complaint of fever, altered sensorium, not oriented to time, place, and person, abnormal body movements, and decreased urine output for 3 days. The patient also had multiple grouped vesicles with polycyclic lesions on the flexors of the left arm and forearm, which were associated with severe pain for 4 days, for which the patient was already started on injection acyclovir by an outside hospital. A dermatologist consult made an impression of herpes zoster with atypical presentation. He was a known case of hypertension, chronic obstructive pulmonary disease, and chronic inflammatory demyelinating polyneuropathy, for which the patient was already on tablet telmisartan, amlodipine, deriphyllin, prednisone, and azathioprine. He was shifted to the ICU for further management. There was no history of loss of consciousness; bilaterally, pupils were normal in size and reactive to light, and plantars were flexors; the tone was reduced in all four limbs, and power was reduced in all four limbs, more in bilateral upper limbs. The patient was started on mechanical ventilation under intravenous fentanyl 50 μg/h because of the poor sensorium, and supportive therapy was also initiated. Cerebrospinal fluid analysis was the only significant finding of increased protein levels of 95 mg/dl. An electroencephalogram was suggestive of gross cerebral dysfunction. MRI of the brain suggested age-related diffuse cerebral atrophy with small vessel ischemic changes. During this period, the patient continued to have poor sensorium with the Glasgow Coma Scale of E1VTM1, so it was diagnosed as encephalopathy under evaluation. On day 14 of the ICU stay, the patient continued to have poor sensorium despite all necessary interventions, so fentanyl infusion was stopped. After 48 h, the patient had good sensorium, spontaneous eye-opening, and following commands with further neurological improvement of tone and power over the next 5 days. Discussion This made us label this case as fentanyl encephalitis because even after directed management, the patient continued to have poor sensorium, which was confounded by fentanyl infusion used for sedation throughout the ICU stay. These neurological sequelae improved without specific treatment. Fentanyl-induced acute encephalopathy is uncommon but can result in considerable functional disability [1]. Fentanyl seldom causes delayed hypoxic leukoencephalopathy, which manifests itself several days to weeks after exposure. There are reports of acute intoxication and delayed encephalopathy with fentanyl patches in elderly patients attributed to periodic anoxia [2,3]. In one of the patients, the acquisition of Fluid Attenuated Inversion Recovery images 40 days after the administration of a fentanyl patch revealed the presence of bilateral symmetrical high signal intensities in the deep and periventricular white matter regions, with no discernible involvement of gray matter. These findings were not previously documented in prior investigations of the same patient [4]. Leukoencephalopathy is not specific to fentanyl but has also been documented with other opioids. In a case report by Morales Odia et al.[5], a 46-year-old man who overdosed on oxycodone developed multifocal encephalopathy and severe cerebellitis, resulting in acute obstructive hydrocephalus. In this patient, an MRI of the brain revealed a nonvascular distribution of diffusion-positive lesions in both cerebellar hemispheres and globi pallidi with intact cerebral perfusion, indicating an inflammatory condition. In a case series of methadone poisoning, eight individuals had acute encephalopathy, whereas two developed delayed-onset encephalopathy [6]. In these patients, diffusion-weighted imaging MRI revealed bilateral confluent or patchy T2 and Fluid Attenuated Inversion Recovery high signal intensity in cerebral white matter, cerebellar involvement, and bilateral occipito-parietal cortex diffusion limitation. Two individuals had internal capsule involvement, while another had abnormalities in the globus pallidus and head of caudate nuclei [6]. Conclusion This emphasizes that clinicians should be aware of encephalopathy from fentanyl use and other opioids as well and be vigilant for the same, especially in the elderly. Thereby considering other drugs in combination with fentanyl to decrease its dose or using intermittent boluses instead to decrease the incidence of this rare phenomenon. Acknowledgements This manuscript is approved by all the authors. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.