The hemodynamic effects of small-volume boluses of hyperosmotic solutions are often deemed negligible in the clinical setting. However, animal studies have reported decreases in systemic arterial blood pressure and bradycardia with the administration of hyperosmotic solutions. This is a report of a 60-year-old woman, intubated and sedated, who developed acute decreases in systemic arterial blood pressure with the administration of ≤50 mL of 50% dextrose. Animal studies suggest that hyperosmolar-induced hypotension may be avoided by administering the hyperosmotic solution slowly. This allows for admixture and therefore a decreased osmotic load at the proposed osmoreceptor involved in the neural reflex.