Groupe Choc, Contrat AVENIR INSERM U 961, Faculté de Médecine, Nancy Université, Nancy, France.
Crit Care Med. 2013 Jan;41(1):195-204. doi: 10.1097/CCM.0b013e318267667b.
Severe hypotension resulting from anaphylactic shock may be refractory to epinephrine and impair cerebral oxygenation and metabolism contributing to anaphylactic shock morbidity and mortality. Refractoriness to epinephrine could be corrected by nitric oxide pathway inhibitors such as methylene blue.
To compare the systemic and regional (brain and skeletal muscle) effects of epinephrine and methylene blue given alone or in combination in a rat model of anaphylactic shock.
Prospective laboratory study.
University laboratory.
Male Brown-Norway rats (n = 60).
After sensitization and induction of anaphylactic shock by ovalbumin, animals received either vehicle (ovalbumin group) or a 3-mg/kg methylene blue bolus (methylene blue group) or epinephrine (epinephrine group) or both (methylene blue-epinephrine group). Sensitized control rats received only vehicle and no ovalbumin (control group).
Mean arterial pressure, cardiac output, cerebral blood flow, skeletal muscular oxygen partial pressure, cerebral oxygen partial pressure, skeletal muscular, and cerebral interstitial lactate/pyruvate ratio were measured. Cleaved caspase 3 and hypoxia-inducible factor-1α expression were analyzed in the cerebral cortex by Western blot. Without treatment, rats died rapidly within 15 mins from a decrease in cardiac output and mean arterial pressure, whereas treated rats survived until the end of the experiment. Methylene blue alone extended survival time but without significant improvement of hemodynamic variables and tissue perfusion and did not prevent neuronal injury. Epinephrine restored partially systemic hemodynamic variables and cerebral perfusion preventing glutamate-induced excitotoxicity. Compared with epinephrine alone, the methylene blue-epinephrine association avoided neuronal excitotoxicity and had an additive effect both on hemodynamic variables and for prevention of brain ischemia. Neither treatment could significantly restore cardiac output or prevent muscular compartment ischemia and microvascular leakage.
Anaphylactic shock is associated with severe impairment of cerebral blood flow despite correction of arterial hypotension. Epinephrine must still be considered as the first-line vasoconstrictive agent to treat anaphylactic shock. The epinephrine-methylene blue association was the most effective treatment to prevent cerebral ischemia and could be used in anaphylactic shock refractory to epinephrine.
过敏性休克引起的严重低血压可能对肾上腺素无反应，并损害脑氧合和代谢，导致过敏性休克发病率和死亡率升高。一氧化氮途径抑制剂如亚甲蓝可纠正肾上腺素无反应。
比较在过敏性休克大鼠模型中，单独使用肾上腺素和亚甲蓝，或联合使用肾上腺素和亚甲蓝对全身和局部（脑和骨骼肌）的影响。
前瞻性实验室研究。
大学实验室。
雄性 Brown-Norway 大鼠（n=60）。
卵清蛋白致敏和诱导过敏性休克后，动物分别给予载体（卵清蛋白组）或 3mg/kg 亚甲蓝推注（亚甲蓝组）或肾上腺素（肾上腺素组）或两者联合（亚甲蓝-肾上腺素组）。未致敏对照大鼠仅给予载体且未给予卵清蛋白（对照组）。
测量平均动脉压、心输出量、脑血流、骨骼肌氧分压、脑氧分压、骨骼肌和脑间质乳酸/丙酮酸比。通过 Western blot 分析大脑皮质中 cleaved caspase 3 和缺氧诱导因子-1α的表达。未经治疗，大鼠在 15 分钟内由于心输出量和平均动脉压下降而迅速死亡，而治疗组大鼠存活至实验结束。亚甲蓝单独使用可延长生存时间，但对血流动力学变量和组织灌注无显著改善，也不能预防神经元损伤。肾上腺素部分恢复了全身血流动力学变量和脑灌注，防止了谷氨酸诱导的兴奋性毒性。与单独使用肾上腺素相比，亚甲蓝-肾上腺素联合避免了神经元兴奋性毒性，并对血流动力学变量和预防脑缺血具有相加作用。两种治疗方法均不能显著恢复心输出量或预防肌肉间隔缺血和微血管渗漏。
尽管纠正了动脉低血压，但过敏性休克仍伴有严重的脑血流受损。肾上腺素仍应被视为治疗过敏性休克的一线血管收缩剂。肾上腺素-亚甲蓝联合是预防脑缺血最有效的治疗方法，可用于治疗对肾上腺素无反应的过敏性休克。
