Adenosine, lidocaine, and Mg2+(ALM) resuscitation fluid protects against experimental traumatic brain injury

作者：Letson Hayley L; Dobson Geoffrey P^*

来源：Journal of Trauma and Acute Care Surgery, 2018, 84(6): 908-916.

DOI：10.1097/TA.0000000000001874

• Traumatic brain injury
• fluid percussion
• inflammation
• ALM
• platelet

BACKGROUND Currently, no drug therapy prevents secondary injury progression after traumatic brain injury (TBI). Our aim was to investigate the effects of small-volume intravenous adenosine, lidocaine, and Mg2+ (ALM) resuscitation fluid after moderate TBI in a rat fluid-percussion injury model.
METHODS Anesthetized, mechanically ventilated male Sprague-Dawley rats (449 5 g) were randomly assigned to one of four groups: (1) sham (craniotomy without TBI), (2) no-treatment, (3) saline-control, or (4) ALM therapy groups (all n = 16). A subdural probe was implanted in eight animals per group to measure cerebral blood flow. Fifteen minutes after moderate TBI was induced with lateral fluid percussion injury (2.57 atm), a single 3% NaCl ALM bolus (0.7 mL/kg) was injected intravenously, and after 60 minutes (Phase 1), 0.9% NaCl +/- ALM stabilization drip (0.5 mL/kg per hour) was administered for 3 hours (Phase 2).
RESULTS Mortality (without subdural brain probe) was 25% (saline controls) and 0% (ALM). Sixty minutes after bolus, ALM significantly increased cardiac function, cortical blood flow (CBF; approximately threefold) and blunted systemic inflammation compared to saline controls. Three hours after infusion drip, ALM improved left ventricular function, supported higher CBF, decreased proinflammatory cytokines systemically (IL-1, tumor necrosis factor , and regulated on activation, normal T cell expressed and secreted [RANTES]), increased anti-inflammatory cytokines in brain tissue (IL-10, IL-4), lowered brain injury markers (neuron-specific enolase, Syndecan-1, HMGB-1), reduced coagulopathy, increased platelet aggregation, and maintained baseline fibrinogen levels. Saline-controls were proinflammatory (brain, heart, lung, and blood) and hypocoagulable with neurogenic enlargement of the right side of the heart. Survival time significantly correlated with plasma neuron-specific enolase (p = 0.001) and CBF at 180 minutes (p = 0.009), and CBF correlated with brain anti-inflammatory cytokines (p = 0.001-0.034).
CONCLUSION After moderate TBI, ALM resuscitation fluid increased survival and protected against early secondary injury by reducing coagulopathy, inflammation, and platelet dysfunction.

• 出版日期2018-6