O3200: Thalami and Dentate Nuclei Involvement in an Infant with Propofol Related Infusion Syndrome

Introduction: Propofol related infusion syndrome (PRIS) is a rare and potentially lethal complication of propofol infusion. The duration of use exceeding 48 hours and the rate of 4 mg/kg /hour are associated risk factors. The syndrome is clinically characterized by multiorgan failure and brain injury has also been reported. We report the first case of symmetric thalami and dentate nuclei involvement with left middle cerebral artery (MCA) stroke in a five-month-old infant who presented with multiorgan failure concerning for PRIS.

Case Description: The patient was a previously healthy five-month-old male who presented to an outside hospital with respiratory failure requiring intubation, and was sedated with dexmedetomidine and fentanyl infusions. After several days, sedation was transitioned to propofol infusion and methadone in anticipation of extubation. Propofol infusion was continued for 55.8 hours with an average dose of 169.7 mcg/kg/min (10.2 mg/kg/hr). He developed cardiac dysrhythmias, acidosis, rhabdomyolysis and acute kidney injury consistent with PRIS. He was transferred due to protentional need for ECMO. Upon arrival he was unresponsive to stimuli with no sedation. On the third day of hospitalization EEG findings revealed discharges from the regions next to the middle cerebral artery (MCA) prompting CT imaging that confirmed the left MCA ischemic stroke. Brain MRI obtained on day 14 of illness showed restricted diffusion in the distribution of the left MCA territory with symmetric restricted diffusion within the cerebral hemispheres, thalami, innominate substance, dentate nuclei and cerebellum (Figure 1 A-F). Follow-up brain MRI showed new areas of diffusion restriction around the infarction and both thalami (Figure 2 A-F). The patient ultimately developed purposeful movement in his left upper extremity and was successfully extubated.

Discussion: Brain injury is not usually associated with PRIS in infants. Reversible symmetric restricted diffusion within the supra- and infratentorial white matter has been previously described by Li et. al. and Pernicone et. al. who reported two cases of PRIS with bilateral restriction diffusion involvement of basal ganglia and cerebellum. However, our case is novel due to the involvement of thalami, innominate substance, and dentate nuclei. Similar diffuse findings have been reported in patients with mitochondrial and peroxisomal β-oxidation of very-long-chain fatty acids suggestive of mitochondrial dysfunction in the pathophysiology of brain lesions. Therefore, the preferential involvement of the highly metabolic regions of the brain may be explained by the impairment in ATP generation thought to underlie the pathophysiology of PRIS. However, a complicating factor is that our patient received methadone, which has been shown to induce both acute and delayed diffuse leukoencephalopathy.

Conclusion: Prompt advanced imaging is critical in unresponsive patients if clinical findings cannot be fully explained by a focal brain lesion. High dose propofol and prolonged infusion should be used with caution to avoid devastating neurologic consequences from PRIS.