Effects of methylene blue and volatile anesthetics on survival in a murine hemorrhage resuscitation model

Background: Hemorrhage is a frequent cause of morbidity and mortality, possibly complicated by volatile anesthetics administered during surgical emergencies. Because methylene blue (MB) was suggested to reduce bleeding, we reasoned that it may improve resuscitation. We used a rat model of controlled and uncontrolled hemorrhage with fluid resuscitation, aiming at high versus low mean arterial pressure (MAP) to assess the role of early MB injection on survival and the effects of different anesthetics on outcome. Methods: Wistar male rats (n = 160) were subjected to 15-minute controlled and 60-minute uncontrolled hemorrhage and received lactated Ringer's solution replacement. Four sets (four groups per set, N = 10 per group) were anesthetized with halothane, isoflurane, sevoflurane, or ketamine (KET; control). Resuscitation-targeted MAP was 80 mm Hg in two groups per set and 40 mm Hg in two groups per set: one group received MB 25 mg/kg intravenously and the other one did not receive. Results: All parameters were worse in the higher target groups compared with the lower MAP target groups. MB improved variable outcomes in the treated compared with the nontreated groups, independent of the MAP or anesthesia agent: the amount of replacement volume, lung tissue xanthine oxidase activity, and rats' survival rates. Outcomes with and without MB were worse in the halothane set, followed, in ascending order, by sevoflurane, isoflurane, and KET. Conclusions: MB improved parameters and survival rates after controlled and uncontrolled hemorrhage and fluid resuscitation, even in high MAP-resuscitated rats. KET seemed to be the best anesthetic choice among the four classic agents tested. The effects of balanced anesthesia and total intravenous anesthesia in similar conditions require additional studies.