使用猪模型评估去甲肾上腺素和肾上腺素在普萘洛尔中毒中的风险和获益。
Use of a Porcine Model to Evaluate the Risks and Benefits of Vasopressors in Propranolol Poisoning.
机构信息
Department of Emergency Medicine, Hennepin Healthcare, 701 Park Ave, Mail Code RL.240, Minneapolis, MN, 55415, USA.
Minnesota Poison Control System, Minneapolis, MN, USA.
出版信息
J Med Toxicol. 2020 Apr;16(2):212-221. doi: 10.1007/s13181-020-00758-8. Epub 2020 Jan 24.
INTRODUCTION
Vasopressors are a commonly used treatment in beta-blocker poisoning despite evidence they may be ineffective or harmful. The primary objective of the present study is to use previously collected data from two prior studies (high-dose insulin (HDI) versus vasopressin + epinephrine and a placebo-controlled HDI study) to compare survival between vasopressin + epinephrine and placebo. Secondary outcomes included a comparison with HDI as well as comparisons with hemodynamic parameters, including mean arterial pressure (MAP), cardiac output (CO), heart rate (HR), and systemic vascular resistance (SVR).
METHODS
Cardiogenic shock was induced in healthy pigs with a bolus of 0.5 mg/kg of intravenous propranolol followed by an infusion of 0.25 mg/kg/minute until the point of toxicity, defined as (0.75 × initial HR × initial MAP), at which point the infusion was reduced to 0.125 mg/kg/minute for 240 (vasopressin + epinephrine or HDI) or 360 minutes (placebo) or until death.
RESULTS
Survival was significantly lower in pigs receiving vasopressin + epinephrine (0%, 0/5) than in pigs receiving placebo (50%, 2/4) (p < 0.01). Survival was significantly higher with HDI compared with both groups (100%, 5/5) (p < 0.01). All vasopressin + epinephrine pigs died within 100 minutes after reaching toxicity. Over the course of the resuscitation, we observed a statistically significant steady decrease in CO and HR in the vasopressin + epinephrine group compared with placebo (p < 0.01). In contrast, we observed a statistically significant change in MAP and SVR that followed a parabolic arc, with MAP and SVR rising significantly initially in the vasopressin + epinephrine group then rapidly falling until death (p < 0.01).
CONCLUSIONS
Mortality was higher with vasopressors compared with placebo in this porcine model of propranolol poisoning. Further studies are warranted to define the optimal timing and role of vasopressors in beta-blocker poisoning.
简介
尽管有证据表明血管加压剂在β受体阻滞剂中毒中的应用可能无效或有害，但它们仍是一种常用的治疗方法。本研究的主要目的是使用之前两项研究（高剂量胰岛素（HDI）与血管加压素+肾上腺素和安慰剂对照的 HDI 研究）中的已收集数据，来比较血管加压素+肾上腺素与安慰剂之间的存活率。次要结局包括与 HDI 的比较，以及对包括平均动脉压（MAP）、心输出量（CO）、心率（HR）和全身血管阻力（SVR）在内的血流动力学参数的比较。
方法
通过静脉注射 0.5mg/kg 的普萘洛尔和持续输注 0.25mg/kg/min 来诱导健康猪发生心源性休克，直至达到毒性终点（（0.75×初始 HR×初始 MAP），此时输注速度降低至 0.125mg/kg/min，持续 240 分钟（血管加压素+肾上腺素或 HDI）或 360 分钟（安慰剂）或直至死亡。
结果
接受血管加压素+肾上腺素治疗的猪的存活率明显低于接受安慰剂治疗的猪（0%，0/5）（p<0.01）。与两组相比，接受 HDI 治疗的猪的存活率显著更高（100%，5/5）（p<0.01）。所有接受血管加压素+肾上腺素治疗的猪在达到毒性终点后 100 分钟内死亡。在复苏过程中，我们观察到与安慰剂相比，血管加压素+肾上腺素组的 CO 和 HR 持续显著下降（p<0.01）。相比之下，我们观察到 MAP 和 SVR 发生了统计学上显著的变化，呈抛物线型，血管加压素+肾上腺素组的 MAP 和 SVR 最初显著升高，然后迅速下降直至死亡（p<0.01）。
结论
在该猪普罗洛尔中毒模型中，与安慰剂相比，血管加压剂的死亡率更高。需要进一步的研究来确定血管加压剂在β受体阻滞剂中毒中的最佳时机和作用。
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