In a double-blind randomized non-inferiority trial, fentanyl given intravenously (IV) at 1.0 µg/kg is compared with fentanyl intranasally (IN) at 1.25 µg/kg, esketamine IV at 0.2 mg/kg, and esketamine IN at 0.625 mg/kg for acute traumatic pain in adults treated by Emergency Medical Services in the Netherlands. The primary outcome is pain reduction on a 0–10 Numeric Rating Scale at 10 minutes after the first dose, with a non-inferiority margin of 1.0. The trial aims to determine whether the alternative routes and drugs are as effective and safe as intravenous fentanyl, addressing a gap in comparative evidence for prehospital pain management.
A new method combining two brain imaging techniques—pharmacological MRI and pharmacological MRS—was tested in 32 healthy adults given S-ketamine or placebo. S-ketamine caused strong blood-flow changes in frontal, cingulate, and insular brain regions, which matched patterns of glutamate and opioid receptors and correlated with participants' reports of dissociation. These blood-flow changes occurred alongside increases in brain glutamate and lactate, especially at higher doses. Combining both imaging methods improved the ability to predict whether a person had received placebo, a low dose, or a high dose of S-ketamine. The findings show that simultaneously measuring blood flow and brain chemistry provides complementary insights into how drugs affect the brain.