key: cord-1017380-per93s46 authors: Eliliwi, Mouhanned; Meyfeldt, Jennifer; Hart, Stephanie; Friedman, Eliot title: METHYLENE BLUE IN REFRACTORY SEPTIC SHOCK date: 2020-10-31 journal: Chest DOI: 10.1016/j.chest.2020.09.155 sha: ddebd035d878a2e125f0e8602fbe47f126e0b47c doc_id: 1017380 cord_uid: per93s46 nan Refractory septic shock is characterized by persistent hypotension with end-organ damage due to an underlying infection that fails to respond to maximal vasopressor support. Beyond IV fluids and antibiotics, treatment options are limited. Here, we present a case of refractory septic shock that rapidly improved following methylene blue (MB) administration. An 82-year-old man with a past medical history of coronary artery disease presented to the hospital with one week of altered mental status and dyspnea. He was tachycardic to 159 bpm, hypotensive to 64/41 mmHg, and tachypneic. Bloodwork revealed mild leukopenia, acute kidney injury, and severe metabolic acidosis with pH 7.15 and lactate 10.7 mmol/L. A nasopharyngeal swab for SARS-CoV-2 was positive. Urinalysis was concerning for infection. CT chest showed bilateral patchy airspace opacities consistent with multifocal pneumonia. The patient was intubated for airway protection and administered IV fluids, piperacillin-tazobactam, and vancomycin. Despite aggressive fluid resuscitation, he remained persistently hypotensive, necessitating maximum dosages of norepinephrine, vasopressin, epinephrine, and phenylephrine infusions. Point-ofcare ultrasound revealed preserved cardiac function. The decision was made to administer MB at 1 mg/kg over one hour. Within 3 hours, epinephrine infusion was successfully weaned off. Phenylephrine infusion was discontinued 24 hours later. Vasopressin and norepinephrine infusions were successfully stopped by hospital day 4 and 6, respectively, and patient's shock had resolved. Urine culture grew Escherichia coli. Antibiotic regimen was narrowed to ceftriaxone. The patient was extubated on hospital day 6 and was discharged home on hospital day 13. In septic shock, uncontrolled cytokine and nitric oxide (NO) lead to loss of vascular tone, which results in inadequate tissue oxygenation and end-organ damage. MB inhibits guanylate cyclase, which is a second messenger in NOmediated vasodilatation. Several studies have noted a decrease in vasopressor requirements and preservation of cardiac performance markers (such as left and right ventricular stroke work index) when comparing MB to placebo in refractory septic shock; however, current literature does not suggest a reduction in mortality or length of hospital stay. Pulmonary vasoconstriction resulting in hypoxia was the most serious adverse effect, but was only noted with higher MB dosing (3-4 mg/kg). This case supports the previously described beneficial effects of MB and suggests that further trials should be conducted to assess the effect of MB on clinical outcomes. CONCLUSIONS: This case highlights the potential role of MB in refractory septic shock. Its use is considered safe when administered in low doses. Inhibition of nitric oxide synthesis by methylene blue Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study The influence of methylene blue infusion on cytokine levels during severe sepsis