β受体阻滞剂过量，怎么办？
感谢战友妞酱对微信公众号【啰嗦探案 临床实战】的友情投稿！
β受体阻滞剂应用推荐
对乙酰氨基酚过量，用N-乙酰半胱氨酸解救；
安眠药过量，用安易醒解救；
吗啡中毒，用纳洛酮解救；
那β受体阻滞剂过量，怎么办？
给肾上腺素有用吗？
有没有特效药解救？
你有没有遇到过β受体阻滞剂过量？
初入临床，我犯过很多让带教老师想打110的错误。
比如：
有一天，她给我一片倍他乐克片，嘱咐我给24床吃。初入CCU的我，径直走到房间尽头我认为是24床的位置，嘱咐该床老人：我的上级大夫嘱咐您，今天把这个药吃了。然后我就去逛街了。
下午六点左右收到带教老师夺命call：我让你给24加的药呢？！我：我给了她让她吃了啊……带教：你给错人了！你把药发给22床了！你给病人吃药，都不核对床号吗？！护士都说三查八对……
我心里冒冷汗，满脑子都在想，该怎么处理这个病人，万一药物过量……一路内心跪倒狂奔回医院，老师告诉我，好在，22床那个老太太也不傻，我不是她的管床医生，别人给她的药她是不吃的！
幸好……（虽然一片倍他乐克不太可能中毒）
初入临床犯的错误，一辈子印象深刻。这个病人的事情也一直在警示我。
如果她因为倍他乐克过量了，我该怎么办？
病人β受体阻滞剂过量，有没有特效解毒剂？过量的表现又是什么，如何诊断？
β受体阻滞剂过量，其实并不少见，甚至比文献报道的数量高25倍【1】！（但国内报道少，也没有人用特效药解毒的案例报道）跟大家一起看一个国外的案例：
A 40-year-oldwhite female with a history of severe depres[1]sion and suicidalideations was found unconscious with shallow respirations after reportedlyingesting multiple drugs, includ[1]ing doxepin - 800 rng, propranolol - 2000 mgand an unknown quantity of diazepam. Initially, her systolic BP was 90 mm Hgbut subsequently fell to 70 mm Hg, at which time pneumatic trousers were placedand inflated. Her pulse rate at this time was 60/min. In route to the hospital,the patient was given naloxone 0.4 mg and dextrose 50010 50 ml iv.
一名40岁白人女性患有严重抑郁伴随自杀观念，自诉服用过多种药物，包括多塞平800 ng，普萘洛尔2000 mg和未知量的地西泮，服用后后发现自己呼吸困难。她的收缩压从开始的90mmHg降至70mmHg，医生给予了其体外反搏术。此时的脉搏速率为60 / min。在去医院的途中，给予患者静脉注射纳洛酮0.4 mg和右旋糖酐 50 ml。
Upon arrival atthe emergency department, the patient was unresponsive with shallowrespirations, midpoint and reactive pupils, and no spontaneous movements. Hersystolic BP at this time was 70 mmHg, with a heart rate of 80/min. The patientwas intubated endotracheally, a subclavian line was inserted, and a dopamineinfusion (400 mg in NaCI 0.9% 250 ml) was started at a rate of 10-15 μg/kg/min.
到达急诊室后，患者无应答、呼吸浅、瞳孔居中对光反射正常，无自主运动。此时SBP70mmHg，HR 80 / min。对该患者进行气管插管，并以“10-15Ig / kg / min”速率输注多巴胺（400 mg溶于0.9％250 ml NaCl）。
The duration of the QRS complex at this timewas 0.06 sec. A #34 French Ewald tube was inserted orally for gastric lavagewith initial returns of purple pill fragments.Gastric lavage was performed withtap water to clear returns and a charcoal slurry 50 g, along with sodiumsulfate 50% 30ml were administered. Initial arterial blood gases revealed a pHof 7.57, Pco, of 24 mm Hg, Po, of 159 mm Hg, and bicar[1]bonate concentrationof 21 mEq/L, while being ventilated by Ambu bag. Since the systolic BP remainedat 70 mm Hg, the dopamine infusion was increased to 40 μg/kg/min and subsequently to65 μg/kg/min with noeffect on blood pressure,despite a central venous pressure of 18 mm Hg.
QRS间期此时为0.06S。经口插入胃管，洗出紫色药丸碎片，反复盐水洗胃并加入50克木炭浆和50％硫酸钠30ml。初始动脉血气的pH值为7.57，Pco为24 mm Hg，Po为159 mm Hg，双碳酸氢盐浓度为21 mEq / L，同时通过Ambu袋进行通气。由于收缩压保持在70 mm Hg，因此多巴胺输注量增加到40 μg/ kg / min，随后增加到65 μg/ kg / min，尽管中心静脉压为18 mm Hg，但对血压没有影响。
In light of thehistory of propranolol ingestion and no obvious widening of the QRS complextypical of tricyclic antidepressant toxicity, glucagon I mg iv was given withno change in systolic BP.
因有明确普萘洛尔摄入病史且无三环类抗抑郁药中毒的典型QRS波增宽，遂给予胰高血糖素I mg iv，收缩压无变化。
A norepinephrineinfusion (8 mg in 250 ml of NaCl 0.9%) was added and was increased to a rateof75μg/min withsystolic BP increasing slightly to 90 mm Hg. An additional glucagon 5 mg iv wasadministered empirically with an immediate increase in systolic BP to 130 mmHg.
加入去甲肾上腺素输注液（8 mg在250ml NaCl 0.9％中）以75μg/分钟的速率增加，收缩压略微增加至90毫米汞柱。根据经验再次给予胰高血糖素5 mg iv，收缩压立即增加至130 mm Hg。
The dopamine andnorepinephrine infusions subsequently were discontinued.The patient wastransferred to the medical intensive care unit with no change in mental status.An additional bolus of glucagon 5 mg iv followed by a continuous infusion of 10mg/h was used to maintain systolic BP > 100 mm Hg. A serum potassiumconcentration measured 2.5 h after initiation of glucagon therapy was 3.3mEq/L, with a serum pH of 7.6.Potassium supplements were administered byperipheral iv with a subsequent stabilization of the serum potassium at4.8mEq/L.
停止输注多巴胺和去甲肾上腺素，患者转入ICU，精神状态无明显好转。再次静脉推注5 mg胰高血糖素，然后连续输注10 mg / h，维持收缩压> 100 mm Hg。胰高血糖素治疗开始2.5小时后测得的血清钾浓度为3.3 mEq / L，血清pH值为7.6。通过外周静脉内注射补充钾，随后将血钾稳定在4.8mEq / L。
The glucagongradually was weaned to maintain a systolic BP of 100-105 mm Hg and wasdiscontinued after 41 hours of continuous infusion therapy, at which time thesystolic BP was 120-130 mm Hg. The patient regained consciousness the day afterthe ingestion and was transferred two days later for appropriate psychiatrictreatment.
逐渐将胰高血糖素减量并维持100-105 mm Hg的收缩压，并在连续输注治疗41小时后停用，此时收缩压为120-130 mm Hg。停药后第二天患者恢复了意识，两天后被转移到适当的精神科治疗。
The toxicologyqualitative laboratory screen performed on the patient's urine was positive forpropranolol and its metabo[1]lites but negative for phencyclidine,opiates, barbiturates, benzodiazepines, amphetamines, phenothiazines, andcocaine metabolites. A blood analysis was negative for alcohol, bar[1]biturates, and salicylates. Neither blood norurine was tested for tricyclic antidepressants.
患者尿液毒理学定性筛查提示：普萘洛尔及其代谢物（+），而苯环利定，鸦片，巴比妥酸盐，苯并二氮杂，苯丙胺，吩噻嗪和可卡因代谢物（-）。血液分析结果显示酒精、巴比妥酸盐和水杨酸盐呈阴性。血液和尿液均未测出三环类抗抑郁药。
以上是一个1984年的CASE，在治疗时，经验性给予了1至5mg胰高血糖素治疗β受体过量。那么正规的用法如何呢？也要经验性用药吗？
2020年，AHA发布的药物致心律失常的救治指南中给出了推荐剂量：
“其他诱发因素（电解质异常，感染，甲状腺功能减退）也应处理。对于短期管理，阿托品可以每3至5分钟静脉内给药，最大剂量为3 mg。进行过心脏移植而无自主神经支配证据的患者不应接受阿托品治疗，因为它可能导致反常的心脏传导阻滞，甚至导致窦性停搏。
在血流动力学受损但冠状动脉缺血可能性低的患者中，可能需要异丙肾上腺素，多巴胺，多巴酚丁胺或肾上腺素。难治性病例可采用临时经皮或经静脉起搏。
对于过量的窦房结或房室结阻滞剂，根据时机不同，洗胃或活性炭可能有用。对于有症状或血液动力学不稳定的心动过缓伴有β-受体阻滞剂或钙通道阻滞剂过量的患者，以3至10 mg静脉推注胰高血糖素，然后连续输注3至5mg/h。大剂量常规胰岛素（1单位/kg静脉推注，然后连续输注0.5单位/kg/h）可提高心率并改善与房室结抑制药物过量相关的难治性心律失常的血液动力学。静脉右旋糖应同时应用，并应密切监测电解质。钙通道阻滞剂过量的患者可以静脉注射氯化钙或葡萄糖酸钙。”
【1】Peterson C D, Leeder J S, Sterner S,et al. Glucagon Therapy for β-Blocker Overdose:[J].Annals of Pharmacotherapy, 1984, 18(5): 394-398.
【2】Tisdale, J. E., Chung, M. K.,Campbell, K. B., Hammadah, M., Joglar, J. A., Leclerc, J. (2020). Drug-Induced Arrhythmias: A Scientific StatementFrom the American Heart Association. Circulation.
原创作者：妞酱
声明：该文仅代表作者本人观点