Introduction: Dexmedetomidine is an alpha-2 adrenoceptor agonist which is widely used for sedation. Dexmedetomidine does not suppress the respiratory drive and produces a state of cooperative sedation; it may be associated with beneficial outcomes in the general critical care population. The role of dexmedetomidine in the treatment of toxicologic conditions (excluding alcohol withdrawal) is unclear.
Objectives: To critically assess and summarize the literature regarding the use of dexmedetomidine in toxicologic conditions other than alcohol withdrawal.
Methods: We performed a systematic review of the medical literature to identify all existing evidence regarding the use of dexmedetomidine for toxicologic conditions. We excluded reviews and commentary, studies reporting exclusively on alcohol withdrawal, and studies reporting the use of dexmedetomidine to treat iatrogenic sedative withdrawal in the intensive care unit. We also performed a review of the Toxicology Investigators Consortium (ToxIC) database for patients treated with dexmedetomidine.
Results: We identified 98 studies meeting inclusion criteria; 87 of these were case reports or case series, representing 99 unique cases. Eleven articles with other designs were identified, which included 138 patients treated with dexmedetomidine for toxicologic conditions. Ninety-three cases from the ToxIC registry met inclusion criteria. Common indications for dexmedetomidine included stimulant intoxication, sedative withdrawal, serotonin syndrome, antimuscarinic toxidrome, opioid withdrawal, and cannabinoid intoxication. Dexmedetomidine was usually administered by continuous infusion; bolus administration was reported in a minority of cases. Adverse effects were uncommon. The quality of evidence was generally low, given the preponderance of case reports, the rate of missing or poorly reported data, and the near-universal co-administration of other sedatives.
Treatment of stimulant poisoning: Fifty-nine patients with stimulant poisoning were treated with dexmedetomidine. There was reasonably good evidence that dexmedetomidine was helpful in the treatment of stimulant poisoning.
Treatment of sedative withdrawal: Twenty-two patients with sedative withdrawal were treated with dexmedetomidine. Several case reports of very high-quality suggested efficacy of dexmedetomidine for this indication, particularly for baclofen withdrawal.
Treatment of serotonin syndrome: Twenty-six patients with serotonin syndrome were treated with dexmedetomidine. This evidence was of lower quality due to missing clinical details, potential overdiagnosis of serotonin syndrome, and near-universal concomitant treatment with other sedatives.
Treatment of antimuscarinic poisoning: Forty-two patients with antimuscarinic poisoning were treated with dexmedetomidine. This evidence was of low quality and was limited by infrequent use of the preferred antidote, physostigmine.
Treatment of opioid withdrawal: Forty-four patients with opioid withdrawal were treated with dexmedetomidine. This evidence was of low quality due to missing clinical details and near-universal concomitant treatment with other agents. The one high-quality trial reported the use of dexmedetomidine in ultra-rapid opioid detoxification, which is not indicated in modern practice.
Treatment of cannabinoid intoxication: Five patients with cannabinoid intoxication were treated with dexmedetomidine. No definite conclusion can be drawn from the limited available evidence.
Discussion: It is important to distinguish between the use of dexmedetomidine as a general sedative, which is likely to increase as the overall utilization of dexmedetomidine in critical care settings increases, and the use of dexmedetomidine as a specific pharmacologic treatment for a toxicologic condition. Well-established pharmacologic data from animal and human studies suggest dexmedetomidine counteracts stimulant-induced norepinephrine release. The mechanism by which dexmedetomidine treats sedative withdrawal is unclear. Some animal data show that dexmedetomidine may indirectly suppress serotonin release, which may suggest a role for dexmedetomidine in this condition.
Conclusions: There is a small and generally low-quality body of evidence which suggests that dexmedetomidine may be helpful in the treatment of certain toxicologic conditions, particularly stimulant intoxication and sedative withdrawal. Further high-quality research is needed to clarify the role of dexmedetomidine in patients with toxicologic conditions.
Keywords: Dexmedetomidine; antimuscarinic; cannabinoid; opioid withdrawal; sedative withdrawal; serotonin syndrome; stimulant.