Septic shock is a major cause of morbidity and mortality in the intensive care unit, and effective therapies are limited. Methylene blue is a selective inhibitor of guanylate cyclase, a second messenger involved in nitric oxide-mediated vasodilation. The use of methylene blue in the treatment of septic shock has been repeatedly evaluated over the past 20 years, but data remain scarce. To evaluate the safety and efficacy of methylene blue for the treatment of septic shock, we conducted a literature search of the EMBASE (1974-June 2009), MEDLINE (1966-June 2009), and International Pharmaceutical Abstracts (1970-June 2009) databases. All available studies published in English were reviewed. Observational studies with methylene blue have demonstrated beneficial effects on hemodynamic parameters and oxygen delivery, but use of methylene blue may be limited by adverse pulmonary effects. Methylene blue administration is associated with increases in mean arterial pressure while reducing catecholamine requirements in patients experiencing septic shock; however, its effects on morbidity and mortality remain unknown. Well-designed, prospective evaluations are needed to define the role of methylene blue as treatment of septic shock.

Background Sepsis and septic shock remain a significant burden on the US healthcare system. A multidisciplinary response system (Coordinated Response To Sepsis, CaRTS) that included a pharmacist responder was implemented for patients with newly suspected sepsis. Objective Evaluate the time to appropriate antibiotic administration among patients with the CaRTS intervention compared to historical controls. Methods The CaRTS intervention included an electronic order set as well as activation of a multidisciplinary team of pharmacy and nursing personnel to coordinate resuscitation and medication administration. The CaRTS group was compared to historical controls. The primary outcome of the study was the proportion of patients with appropriate antibiotic administration within 1 hour of recognition of sepsis. Secondary outcomes included achievement of mean arterial pressure (MAP) ≥65 mmHg and central venous pressure (CVP) of 8–12 mmHg within 6 hours. Results The CaRTS intervention was used for 49 patients and 59 historical controls were included for analysis. Patients with the CaRTS intervention had a greater than 20x higher odds of antibiotic administration within 1 hour compared to controls (Odds Ratio (OR) 22.4, 95% Confidence Interval (CI): 7.5–69) and were more likely to have a CVP ≥8 mmHg at 6 hours (OR 2.4, 95% CI: 1.0–5.6) compared to controls. CaRTS patients achieved non-statistically significant increases in MAP ≥65 mmHg (OR 2.2, 95% CI: 0.7 – 7.7). Conclusions Utilization of a multidisciplinary sepsis bundle that included a pharmacist responder improved the proportion of patients receiving appropriate antibiotics within 1 hour of recognition of sepsis compared to historical controls.

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Pharmacist assessment of patients in septic shock offers the opportunity to improve SSAT. Systems designed to use a pharmacist responder for the care of patients with septic shock maximize the selection of antimicrobials, facilitate rapid administration, and improve surrogate outcomes for mortality in septic shock.