Sudden death in patients receiving drugs tending to prolong the QT interval

AIMS

To examine risks of sudden death in the community associated with drugs grouped by their risk of causing torsades de pointes (TdP) and to explore the risks for individual drugs.

METHODS

Case–control study comparing prior drug intakes and morbidities, using the Arizona classification of drugs causing TdP. Participants included 1010 patients dying suddenly where post-mortem examination did not identify a clear cause of death, and 3030 matched living controls from primary care.

RESULTS

Noncardiac drug risk was posed by antipsychotics and antidepressants. Significantly raised odds ratios (ORs) were found for takers of typical and atypical antipsychotics, ORs [95% confidence interval] 3.94 (2.05, 7.55) and 4.36 (2.54, 7.51), and of selective serotonin reuptake inhibitors [SSRIs] rather than tricyclic antidepressants, ORs 2.21 (1.61, 3.05) and 1.44 (0.96, 2.13). No significant risk was associated with other, noncardiac or psychiatric drugs, OR 1.09 (0.85, 1.41). Arizona classified drugs considered to raise risk of TdP were associated with raised risk of sudden death, as were those only weakly associated with TdP and not considered to pose a risk in normal use, ORs 2.08 (1.45, 3.00) and 1.74 (1.33, 2.28), respectively.

CONCLUSIONS

Atypical and typical antipsychotic drug use were both strongly associated with raised risks, as were SSRIs. Tricyclic antidepressants were not associated with raised risks. The Arizona classification of risk of TdP was a poor predictor of likelihood of noncardiac drug-associated sudden death.     

致心律失常性右室心肌病的临床分析

目的探讨致心律失常性右室心肌病(ARVC)的临床特点。方法回顾分析符合欧洲心脏病协会ARVC诊断标准的15例患者的临床表现、心电图、超声心动图、MRI及电生理检查等,评价ARVC的检查手段及治疗方法。结果 15例患者均有心悸,其中13例有晕厥,有右室扩大及明确右室心力衰竭临床表现者7例。5例静息心电图出现Epsilon波,10例表现为平均QRS时程延长(≥110 ms),13例记录到室性心动过速。15例患者超声心动图均提示右室受累。治疗上以药物治疗为主,经导管射频消融治疗者2例,1例患者植入ICD。结论 ARVC临床表现隐匿,典型者常以反复发作性室性心动过速、晕厥、猝死为首发症状,部分呈家族遗传倾向。Epsilon波、右胸导联QRS波时限≥110 ms及T波倒置是其特征性心电图表现。经导管射频消融治疗室性心动过速成功率低,药物治疗效果不佳,埋藏式心脏转复除颤器治疗较为可行。     

Domperidone-Associated Sudden Cardiac Death in the General Population and Implications for Use in Patients Undergoing Hemodialysis: A Literature Review

Background:

Domperidone, an effective prokinetic agent, is commonly used to manage symptoms of gastroparesis. Health regulatory agencies have issued warnings about an increased risk of sudden cardiac death associated with use of this drug.

Objective:

To evaluate the evidence for domperidone-associated sudden cardiac death and to determine whether this drug can be safely used for gastroparesis in patients undergoing dialysis.

Data Sources:

Two databases (MEDLINE [1965 to September 2014] and Embase [1980 to September 2014]) were searched using the Medical Subject Headings “domperidone”, “sudden cardiac death”, and “cardiac arrhythmia”. The search was limited to studies conducted in humans and published in English. Advisories from health regulatory agencies (Health Canada, the European Medicines Agency, and the US Food and Drug Administration) were identified and reviewed.

Study Selection:

Studies eligible for inclusion in this narrative review were randomized controlled trials and cohort, case–control, cross-sectional, and other epidemiological studies comparing use and non-use of domperidone for the outcome of sudden cardiac death in adults. Abstracts of eligible case reports and case series were also included.

Data Synthesis:

Despite inconsistencies in their decisions, the various drug regulatory authorities have acknowledged the potential safety concern of increased risk of sudden cardiac death associated with domperidone. To date, no randomized controlled studies have shown an increased risk of this outcome secondary to domperidone use. Current regulatory recommendations and approval decisions are based on 2 large observational epidemiological studies that generated a signal of increased risk. The strengths and limitations of these studies were evaluated in detail. No direct evidence applicable to patients with end-stage renal disease was found. In vitro evidence suggests that the risk of sudden cardiac death is dose-related.

Conclusions:

Given gaps in the literature, use of domperidone for patients undergoing dialysis should be assessed on a case-by-case basis. Extreme caution should be used for patients taking more than 30 mg/day of this drug.     

The prevention of sudden death in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a familial myocardial disease caused by mutations in cardiac sarcomeric proteins. HCM is characterised by myocyte disarray and myocardial fibrosis. Most patients are largely asymptomatic but some are prone to a number of disease-related complications, the most problematic of which is sudden cardiac death. Diagnosing patients who are at risk has not been easy because of the clinical heterogeneity of the disease, the frequent absence of symptoms prior to sudden cardiac death and the relatively low disease prevalence and annual mortality rates. To date, both low-dose amiodarone and internal cardioverter/defibrillator inplantation have been advocated in high-risk individuals. Further improvements in clinical understanding and risk stratification are necessary to identify HCM patients who are at high risk of sudden death.     

氟罗沙星静脉滴注过程中患者突然死亡

1例40岁女性患者，因患急性肾盂肾炎，先给予头孢噻肟钠2g溶入0．9％氯化钠注射液250ml静脉滴注，未见不良反应。其后给予氟罗沙星0．4g＋5％葡萄糖注射液500ml静脉滴注。在输入氟罗沙星注射液约250ml时，出现寒战，查BP100／70mmHg，HR84次／min。停止输液，给予异丙嗪肌内注射、地塞米松静脉推注。约17min后患者突然四肢抽搐，血压未测及，心脏停搏，随后呼吸停止。经持续抢救无效死亡。     

肺动脉栓塞猝死的病理学观察

我们遇到3例罕见的肺动脉栓塞引起猝死的尸检例。男2例,女1例,年龄分别是32岁、28岁和26岁。生前1例因头部外伤脑血肿入院,1例因左上肢肱骨患伊文氏瘤入院,1例是患伤寒病后期。2例为肺动脉血栓栓塞,1例为瘤栓栓塞。3例均引起猝死。结合病例对猝死的概念、时限、和发生机理等进行较为深入的病理学分析。     

无临床表现的冠心病猝死的病理学研究

作者从冠心病的尸检例中选出死前无冠心病临床表现的6例猝死病例结合对照组进行分析。结果发现:2例左室前壁大范围心肌梗死,2例冠状动脉开口狭窄和闭塞,2例窦房结动脉管壁增厚、管腔狭窄和结细胞轻度变性。引起猝死的诱因多为过劳,精神紧张,过敏和上呼吸道感染等。     

13例肺动脉栓塞引起猝死的病理学研究

我们遇到13例肺动脉栓塞引起猝死病例,男11例,女2例,年龄最小26岁,最大48岁,7例为下肢被车撞伤和股骨骨折引起肺动脉血栓栓塞,原因不明猝死1例,头部外伤脑血肿入院1例,左上肢肱骨患尤因肉瘤入院1例,伤寒病后期,颈静脉损伤,右心房损伤,空气栓塞于肺动脉引起猝死各1例,结合病例对肺动脉栓塞的种类及发生,猝死发生的机理等方面进行了较为深入的病理学分析。     

心脏性猝死病因及高危因素分析

目的探讨心脏性猝死(SCD)的病因及高危因素。方法回顾性分析97例SCD临床资料。结果冠心病69例(71.1%),其中急性心肌梗死(AMI)35例(36.1%)、慢性充血性心力衰竭(CHF)53例(54.6%),其中纽约心功能分级(NY-HA)Ⅱ～Ⅲ级占86.7%,左室射血分数(LVEF)测定57例,LVEF<55%占84.2%,B型利钠肽(BNP)明显升高26例(26.8%)、临终前心电图示室性心律失常73例(75.3%)、低钾血症26例(26.8%)、冬季SCD最常见(42.2%)、其中6:00—12:00时SCD发生率最高(38.1%)。结论冠心病是SCD最常见的病因;SCD发生有明显的季节性和昼夜差;室性心律失常、心力衰竭、LVEF降低、BNP升高、低钾血症是SCD的高危因素。     

3例隐匿型冠心病猝死的病理学研究

随着社会的发展,冠心病的发病率日益增高,然而有些人尽管患有冠心病,但却无临床表现,有的甚至心电图也显示正常,这些隐匿型冠心病患者在日常生活中以及在医疗实践中常因突意外地死亡地引起纠纷。为此本文作者从冠心病的尸检例中选出死前无冠心病临床表现的３例猝死病例进行分析。     

脂肪心猝死的法医病理学研究

作者从脂肪心的尸检例中选出生前既无心脏病临床表现又无其他致死因素的9例猝死病例,结果发现:右心室心肌约1/2脂肪化的2例,4例右心室心肌全层脂肪化,右心室及心尖部心肌脂肪化者3例。脂肪心病例的右心室肌脂肪含量测定增高平均值达44.8%,并对脂肪心的概念、发生机理和对人体的危害进行简要探讨。     

Ketamine-induced ventricular structural, sympathetic and electrophysiological remodelling: pathological consequences and protective effects of metoprolol

BACKGROUND AND PURPOSE

Growing evidence suggests that long-term abuse of ketamine does harm the heart and increases the risk of sudden death. The present study was performed to explore the cardiotoxicity of ketamine and the protective effects of metoprolol.

EXPERIMENTAL APPROACH

Rats and rabbits were divided into control, ketamine, metoprolol alone and ketamine plus metoprolol groups. Ketamine (40 mg·kg⁻¹·day⁻¹, i.p.) and metoprolol (20 mg·kg⁻¹·day⁻¹, p.o.) were administered continuously for 12 weeks in rats and 8 weeks in rabbits. Cardiac function, electrophysiological disturbances, cardiac collagen, cardiomyocte apoptosis and the remodelling-related proteins were evaluated.

KEY RESULTS

Rabbits treated with ketamine showed decreased left ventricular ejection fraction, slowed ventricular conduction velocity and increased susceptibility to ventricular arrhythmia. Metoprolol prevented these pathophysiological alterations. In ketamine-treated rats, cardiac collagen volume fraction and apoptotic cell number were higher than those of control animals; these effects were prevented by co-administration of metoprolol. Consistently, the expressions of poly (ADP-ribose) polymerases-1, apoptosis-inducing factor and NF-κB-light-chain-enhancer of activated B cells were all increased after ketamine treatment and sharply reduced after metoprolol administration. Moreover, ketamine enhanced sympathetic sprouting, manifested as increased growth-associated protein 43 and tyrosine TH expression. These effects of ketamine were prevented by metoprolol.

CONCLUSIONS AND IMPLICATIONS

Chronic treatment with ketamine caused significant ventricular myocardial apoptosis, fibrosis and sympathetic sprouting, which altered the electrophysiological properties of the heart and increased its susceptibility to malignant arrhythmia that may lead to sudden cardiac death. Metoprolol prevented the cardiotoxicity of ketamine, indicating a promising new therapeutic strategy.     

复方托吡卡胺滴眼液致突发性耳聋

1名60岁女性糖尿病患者，行眼底检查前用复方托吡卡胺滴眼液散瞳，随后出现听力明显下降伴耳呜，检查提示双耳感音神经性耳聋。经高压氧、葛根素治疗后，听力明显恢复。因眼科检查需要，再次用复方托吡卡胺滴眼液，用药后患者又出现听力明显下降，经对症治疗后好转。当患者第4次使用该药后出现耳聋，治疗1月余，听力仍未恢复。     

Antipsychotic-induced sudden cardiac death: examination of an atypical reaction

Following the publication of a recent study, which linked antipsychotics to sudden cardiac death, the safety of both typical and atypical antipsychotics has once again been questioned. Sudden cardiac death resulting from ventricular arrhythmias remains a significant public health concern, with over 300,000 deaths per year in the US alone. Long QT syndrome (LQTS) is an important cause of sudden cardiac death in which both congenital and acquired lesions in cardiac ionic channels impair myocardial repolarization and predispose the heart to developing lethal ventricular rhythms, including torsade de pointes, which may degenerate into ventricular fibrillation. Congenital LQTS is a relatively rare condition; however, acquired LQTS and arrhythmogenesis occurring through the unwanted pharmacological effects of a wide range of medications has become one of the largest problems facing the pharmaceutical industry today. This article examines recent findings linking antipsychotics to ventricular arrhythmias and explores potential new strategies to reduce the incidence of drug-induced sudden cardiac death.     

Sudden unexpected death in infants under 3 months of age and vaccination status- -a case-control study

AIMS: To determine whether DTPP+Hib vaccination (diphtheria, tetanus, pertussis, poliomyelitis +/- haemophilus) increased the risk of sudden unexpected death (SUD) in children under 3 months of age. METHODS: We conducted a multicentre case-control study in the 28 French 'SIDS Centers'. Case selection was based on death labelled sudden infant death syndrome (SIDS) of an infant aged between 30 and 90 days. Three living controls were selected, matched for sex, gestational age and born immediately after the victim in the same maternity unit. RESULTS: We identified 114 cases of SUD aged between 30 and 90 days and 341 live controls matched for age and sex and born in the same maternity unit as the case. DTPP+/-Hib immunization did not increase the risk of SUD (OR 1.08) (95% CI 0.49, 2.36) in children under 3 months of age when adjusted for sleeping position, illness in the week before death, maternal tobacco consumption, birth weight, type of mattress, breastfeeding and sex. However, low birth-weight (6.53 [2.29, 18.9]), multiple birth (5.1 [1.76, 15.13]), no breastfeeding (1.77 [1.1, 2.85]), prone sleeping position (9.8 [5, 8, 18, 9]), soft mattress (3.26 [1.69, 6.29]), recent illness (3.44 [1.84, 6.41]) and parental smoking (1.74 [1.2, 2.96]) were confirmed as risk factors in early SIDS. CONCLUSIONS: DTPP+/-Hib immunization is not a risk factor for early SUD. In this population, we found the same risk factors as described for SIDS.