Fatality involving complications of bupivacaine toxicity and hypersensitivity reaction

This case represents unusual findings of elevated bupivacaine and tryptase concentrations following local anesthetic, bupivacaine, administered as a scalene nerve block for elective rotator cuff repair surgery. Following bupivacaine injection, the patient exhibited almost immediate seizure activity, bradycardia, and cardiac arrest. Resuscitative efforts including cardiopulmonary bypass restored a cardiac rhythm. However, the clinical medical status of the patient progressively declined and he died 7 h following administration of the local anesthetic. Autopsy revealed several abnormalities of the heart including cardiomegaly, myocardial bridging, and lipomatous hypertrophy of the intraatrial septum, which may have contributed to bradycardia and arrhythmia. Postmortem toxicology results revealed elevated bupivacaine and tryptase concentrations. Elevated postmortem bupivacaine concentrations 7 h following administration and abrupt onset of seizures indicate unintentional intravascular injection instead of nerve and tissue infiltration. An elevated postmortem tryptase concentration points to the possibility of a hypersensitivity reaction to bupivacaine.     

类胰蛋白酶与过敏性休克死亡的法医学鉴定

目的探讨类胰蛋白酶与过敏性休克的关系。方法从类胰蛋白酶的生物学特性、正常人分布、检测方法及其与过敏性休克的关系,并应用ELISA方法检测三例尸体血清类胰蛋白酶的浓度,对三例过敏性休克死亡的案例作回顾性分析。结果两例血清中类胰蛋白酶的含量分别为52ng/ml和121ng/ml(高于正常值10倍以上),另一例浓度为0.73ng/ml。结论诊断过敏性休克,类胰蛋白酶含量的检测是很有意义的,但不能单凭检测结果下结论。     

Immunohistochemical quantification of pulmonary mast-cells and post-mortem blood dosages of tryptase and eosinophil cationic protein in 48 heroin-related deaths

Recent studies suggest that many fatal heroin overdoses are caused by anaphylactoid reaction. In the present study we measured tryptase and eosinophil cationic protein in post-mortem blood of 48 deaths after heroin injection. We also investigated the presence and pulmonary distribution of mast-cells using specific immunohistochemical antibody for tryptase and morphometric evaluation in those cases of heroin-related deaths. The data were compared with 44 subjects who died following head trauma and to 32 cases of fatal anaphylactic shock. In the heroin-related death cases, the measurements of serum tryptase levels and eosinophil cationic protein dosages resulted in particularly elevated concentrations compared with the trauma cases. Nevertheless, the data that our study supplies by immunohistochemical techniques indicate that when mast-cells count in the lung was determined, no definite pattern was obtained between fatal heroin overdose cases and the control groups. Furthermore, the wide range of morphine concentrations found in post-mortem blood samples suggest that the term ‘overdose’ is relative and does not sufficiently characterize death associated with heroin addiction. Our study confirms that elevated concentrations of serum tryptase are associated with many heroin-related deaths. At this moment to attribute the cause of these deaths to ‘heroin overdose’ ignores the likely causal contribution of other possible systemic reactions to the mechanism of death.     

豚鼠过敏性休克肺组织中类胰蛋白酶和胃促胰酶的表达

目的观察豚鼠过敏性休克死亡肺组织中类胰蛋白酶和胃促胰酶的表达情况,试图为过敏性休克死亡提供客观的诊断依据。方法健康豚鼠24只,随机均分为实验组和对照组,每组再分死亡即时组、冷藏48h组和冷冻7d组,每组4只。实验组将0.5mL人混合血清用生理盐水1∶10稀释,注射于豚鼠后掌皮内,致敏后3周以人混合血清1mL注入心腔诱发过敏性休克致死;对照组采用生理盐水代替混合血清。提取豚鼠心血及肺组织,应用免疫组化染色和图像分析技术观察类胰蛋白酶和胃促胰酶的表达情况。结果对照组豚鼠肺组织中类胰蛋白酶和胃促胰酶阳性细胞数量较少,分布在小血管和小气管周围。实验组肺组织中类胰蛋白酶和胃促胰酶阳性细胞明显增多,多数细胞形态不规则,阳性染色颗粒脱出肥大细胞并弥散到组织间隙。冷藏48h和冷冻7d的条件下对这两种酶的表达无明显影响。结论过敏性休克致死豚鼠肺组织中类胰蛋白酶和胃促胰酶的表达明显增强,在冷藏48h和冷冻7d内的条件下,可作为过敏性休克死亡的一项诊断依据。     

实验性兔羊水栓塞肥大细胞类胰蛋白酶的含量变化

目的观察家兔羊水栓塞 (AFE)后肺组织中肥大细胞类胰蛋白酶 (MCT)含量的变化。方法分别于健康怀孕家兔耳缘静脉注入羊水、制造羊水栓塞的动物模型 ;取肺组织进行HE染色和免疫组织化学MCT染色 ,镜下观察AFE兔肺组织中MCT的变化。结果对照组兔肺组织MCT呈弱阳性反应 (平均阳性细胞计数 11 2 5个 ) ,注入羊水组和注入胎盘提取液与羊水混合液组肺组织中MCT呈强阳性反应 (平均阳性细胞计数分别为 3 2 98和 45 5 3个 )。结论在羊水栓塞时兔肺组织MCT含量增加     

肥大细胞类胰蛋白酶的免疫组化染色观察

目的　观察过敏性休克死亡者咽喉、肺、小肠组织肥大细胞类胰蛋白酶 (MCT) ,探讨过敏性休克死亡法医鉴定的形态学依据。方法　交通事故致严重颅脑损伤死亡者 10例 (对照组 )、明确诊断为过敏性休克死亡者 15例(实验A组 )和羊水栓塞死亡者 8例 (实验B组 )的尸体 ,分别取其咽喉部、肺及小肠组织 ,石蜡切片 ,HE染色及用免疫组化超敏SP法进行MCT染色。结果　实验A组的咽喉部组织充血、水肿 ,咽喉部粘膜下层MCT增多 (MCT颗粒计数为 48 2 3 ) ;实验B组的咽喉部粘膜下层MCT增多 (MCT颗粒计数为 42 72 )。肺间质尤其是小支气管壁及小血管壁上MCT增多 (MCT颗粒计数分别为 46 98和 43 5 0 ) ,小肠粘膜层MCT增多 (MCT颗粒计数分别为 48 2 3和 42 72 )。对照组的咽喉部、肺和小肠MCT颗粒计数较少 ,分别为 7 79、 12 94和 2 0 2 5。实验A组与对照组相比 ,两组具有显著性差异 (P <0 0 1) ;实验A、B组相比 ,两组无显著性差异 (P >0 0 1)。结论　过敏性休克及羊水栓塞死亡的尸体 ,其咽喉部组织、肺组织及胃肠道组织MCT增多。     

过敏性休克死亡法医学诊断的研究现状

过敏性休克死亡在临床医学及法医学鉴定中较为常见,但过敏性猝死的死后诊断一直是法医病理学鉴定的一大难点。近年来,国内外学者研究了过敏性死亡血清IgE、组胺、肥大细胞类胰蛋白酶和P物质的含量以及其在肺脏和胃肠等组织中的免疫表达,试图为过敏性猝死的法医学鉴定提供客观、准确的形态学依据和诊断指标。本文就过敏性休克死亡法医学诊断的研究进展和存在的问题加以综述。     

Anaphylaxis After the Injection of Buprenorphine

Cause of death rulings in cases when the concentration of a drug or drugs is higher than observed following therapeutic use are generally straightforward “drug deaths.” However, when toxicology testing identifies drug concentrations consistent with therapeutic use or detects no drugs at all, then the cause of death determination is more complicated. Given the rapidity and protean manifestations of anaphylaxis, it should be considered in deaths where no other cause of death is apparent in a suspected drug death. This article reports two cases where an anaphylactic reaction was observed following either the actual or alleged use of therapeutic formulations of buprenorphine intravenously.     

Postmortem Serum Tryptase Levels with Special Regard to Acute Cardiac Deaths

An elevated serum tryptase concentration is considered a specific marker for systemic mast cell activation, a central feature of anaphylaxis. However, in some cases of acute cardiovascular death, high concentrations of serum tryptase are also observed. We compared the postmortem serum tryptase concentrations in 74 cases assigned to the following four groups: anaphylactic deaths (Group A, n = 20), acute cardiac deaths (Group ACD, n = 30), acute dissecting aneurysm ruptures (Group ADA, n = 10), and controls (Group C, n = 14). Additionally, the cutoff between Group A and the other groups was calculated using receiver‐operating characteristic (ROC) curve analysis. Tryptase concentrations were markedly elevated in Group A (p < 0.001), Group ACD (p = 0.015), and Group ADA (p = 0.005). The optimal cutoff was 43 ng/mL, the sensitivity was 90%, and the specificity was 98%. While elevated concentrations of tryptase were noted in practical autopsy cases, due attention should be paid to the differential diagnosis between anaphylactic and acute cardiovascular deaths.     

豚鼠过敏性休克类胰蛋白酶活力测定

目的探索过敏性休克法医学客观诊断标准。方法建立豚鼠异种血清过敏性休克模型,采用专性底物对模型鼠的血清,肺,气管类胰蛋白酶活力进行测定。结果过敏性休克豚鼠血清,肺,气管类胰蛋白酶活力均增加,且三者增加的程度是平行的。结论过敏性休克时,血清,肺,气管类胰蛋白酶活力增加可作为法医检案客观诊断标准。