Vasoplegic Shock Treated with Methylene Blue Complicated by Severe Serotonin Syndrome.

INTRODUCTION: Management of severe vasoplegic shock in overdose can be very challenging. We describe a case of severe refractory vasodilatory shock in poisoning where methylene blue (MB) was used with success. However, the patient subsequently developed severe Serotonin Syndrome (SS) as a result of an interaction between serotonergic drugs and MB. CASE REPORT: A 15-year-old male developed severe vasoplegic shock 1.5 hours after overdosing on several different medications including quetiapine slow release, quetiapine immediate release, desvenlafaxine slow release, venlafaxine, amlodipine, ramipril, fluoxetine, promethazine and lithium. His vasoplegic shock was resistant to high doses of noradrenaline and vasopressin. MB was administered 6.5 hours post ingestion and within 1 hour there was an improvement in his hemodynamic status and reduction of catecholamine requirements. Twelve hours post ingestion, he developed severe Serotonin Syndrome that lasted 5 days as a result of interaction between MB, a reversible monoamine oxidase inhibitor (MAO-I), and the antidepressants taken in overdose. MB had a calculated half-life of 38 hours. CONCLUSION: MB is a useful additional strategy for severe drug induced vasodilatory shock and may be potentially life-saving. Clinicians should be aware that it can interact with other drugs and cause life-threatening Serotonin Syndrome. Lower doses or shorter durations may be wise in patients at risk of this interaction.

Multiphoton microscopy and fluorescence lifetime imaging provide a novel method in studying drug distribution and metabolism in the rat liver in vivo.

Multiphoton microscopy has been shown to be a useful tool in studying drug distribution in biological tissues. In addition, fluorescence lifetime imaging provides information about the structure and dynamics of fluorophores based on their fluorescence lifetimes. Fluorescein, a commonly used fluorescent probe, is metabolized within liver cells to fluorescein mono-glucuronide, which is also fluorescent. Fluorescein and its glucuronide have similar excitation and emission spectra, but different fluorescence lifetimes. In this study, we employed multiphoton fluorescence lifetime imaging to study the distribution and metabolism of fluorescein and its metabolite in vivo in rat liver. Fluorescence lifetime values in vitro were used to interpret in vivo data. Our results show that the mean fluorescence lifetimes of fluorescein and its metabolite decrease over time after injection of fluorescein in three different regions of the liver. In conclusion, we have demonstrated a novel method to study a fluorescent compound and metabolite in vivo using multiphoton fluorescence lifetime imaging.

Alpha-turn mimetics: short peptide alpha-helices composed of cyclic metallopentapeptide modules.

Alpha-Helices are key structural components of proteins and important recognition motifs in biology. Short peptides (