Comments on: Methylene blue? therapeutic alternative in the management of septic shock refractory to norepinephrine

It is a comment on an interesting case report focusing on the use of methylene blue in septic shock refractory to noreprinephrine. In septic shock, the response to pathogen-associated molecular patterns (PAMPS) and damage-associated molecu- lar patterns (DAMPS) generates a combination of vasodilation and increased capillary permeability. Capillary leak, coupled with greater vessel capacitance mediated by vasoplegia, may result in absolute or more commonly relative hypovolemia. The L-arginine nitric oxide (NO) pathway plays a pivotal role in regulating cardiovascular hemodynamics and vascular permeability. Methylene blue inhibits inducible NO synthase (NOS) and guanylate cyclase, thereby reversing NO induced vasodilation. In septic shock, it was firstly used at the beginning of the 1990s. This drug has resulted beneficial and safe in randomized clinical trials and case reports. Recently, its clinical use has been deeply reviewed, and we are strongly convinced that it would deserve further attention and prospective, randomized, clinical trials.