Local cutaneous necrosis secondary to a prolonged peripheral infusion of methylene blue in vasodilatory shock

Ann Pharmacother. 2012 Mar;46(3):e6. doi: 10.1345/aph.1Q560. Epub 2012 Feb 28.


Objective: To report a case of methylene blue extravasation and subsequent tissue necrosis in a patient with refractory septic shock.

Case summary: A 47-year-old female presented with febrile neutropenia secondary to chemotherapy. The patient quickly decompensated to refractory septic shock in the critical care unit despite implementation of early goal-directed therapy as well as intravenous norepinephrine and vasopressin to stabilize her hemodynamic status. She received a 16-hour infusion of 1% methylene blue 0.25 mg•kg(-1)•h(-1), titrated up to 0.5 mg•kg(-1)•h(-1), via a peripheral intravenous catheter. Ten hours after the start of the methylene blue infusion, she experienced a local extravasation injury, which led to distal digital necrosis. While her hemodynamic status improved dramatically, allowing discharge from the intensive care unit and eventually to home, the extravasation site became necrotic and required debridement and skin graft.

Discussion: Methylene blue is a vasoactive chemical that has been shown to provide hemodynamic stability in the treatment of refractory septic shock. Methylene blue administration is not considered standard of practice in the treatment of refractory septic shock and many aspects of its dosing, route, duration, and adverse effects are poorly described. As such, there is little guidance for its administration. We postulate that, in our patient, in the presence of systemic vasopressin and norepinephrine, methylene blue caused extensive vasoconstriction at the site of extravasation, resulting in tissue ischemia and necrosis. Tissue necrosis secondary to peripheral intravenous extravasation has not been previously described and is not listed as an adverse outcome on the drug monograph. The Naranjo probability scale indicates that the tissue necrosis was probably caused by the methylene blue extravasation.

Conclusions: To mitigate future risk to limb and skin, we recommend that methylene blue infusions be delivered via central venous catheter. Extra care should be given to patients with risk factors for extravasation, such as sedation, presence of systemic disease, proximal intravenous puncture sites, and improperly placed catheters.

Publication types

  • Case Reports

MeSH terms

  • Female
  • Humans
  • Infusions, Intravenous
  • Ischemia / chemically induced
  • Methylene Blue / administration & dosage
  • Methylene Blue / adverse effects*
  • Middle Aged
  • Necrosis / chemically induced
  • Shock, Septic / drug therapy*
  • Shock, Septic / pathology
  • Skin / drug effects
  • Skin / pathology
  • Vasoconstriction


  • Methylene Blue