Farmakokinetikk og farmakodynamikk ved bruk av intranasal deksmedetomidin hos voksne

Abstract

Background: Delirium is a common and potentially fatal condition, especially seen in elderly patients. Despite the high morbidity, mortality and economic cost associated with delirium, no drug is yet found to be approved, neither as treatment nor as prevention of delirium. Dexmedetomidine, a highly selective α2-agonist, is proven by several studies to reduce the number of cases with delirium. As of now, for adults, the drug is only used intravenously at ICU and PO. This owing to the fact that dexmedetomidine in addition to have a sedative, analgesic and anxiolytic effect, gives hemodynamics changes such as hypotension, hypertension and bradycardia. Intranasally administrated dexmedetomidine is proven in studies to be a safe method of premedication in children and it would be likely that this administration route would be a better option for elderly patients to avoid serious hemodynamic changes. Objectives: To present the evidence of existing studies which have investigated how the intranasal administration route of dexmedetomidine affects hemodynamics compared to placebo and intravenous administration. Blood pressure and heart rate are the main factors studied in our selection. Methods: A systematic literature search was performed in the PubMed database using MeSH terms and search words in “title/abstract”. The purpose of the search was to identify studies which included the use of intranasal dexmedetomidine and studies investigating the relationship between intranasal dexmedetomidine and its effects on hemodynamics. Studies focusing on animal studies and pediatric patients were excluded. Results: A total of 11 studies were found eligible and included in this review. All studies were RCTs. With one exception, all studies were limited to patients aged under 60 years. The majority of the studies observed a significant reduction of blood pressure and heart rate in patients receiving intranasal dexmedetomidine compared to placebo, though these reductions were modest. Only one study reported a patient with symptomatic hypotension and bradycardia that had to be treated. Conclusion: Based on most of the findings in this literature review, the use of intranasal dexmedetomidine in adults appears to be safe considering the modest hemodynamic effects. However, it exists significant knowledge gaps regarding how the effects differs in the elderly population. Future research should focus on the effects of intranasal dexmedetomidine together with multimorbidity and polypharmacy in a larger age range. The medical and economical value of a drug that can prevent and possibly treat delirium in elderly patients is immense.