Window of Opportunity: Flexion Myelopathy After Drug Overdose

Background: Cervical and thoracic flexion myelopathy are uncommon causes of spinal cord injury that can lead to irreversible paralysis, autonomic dysfunction, and death. To the authors' knowledge, this report is the first to describe the natural history of flexion myelopathy and the simultaneous occurrence of cervical and thoracic flexion myelopathy in the setting of drug overdose. Objectives: To report the association of cervical and thoracic flexion myelopathy and drug overdose; to describe the subacute natural history of flexion myelopathy in the setting of drug overdose; to emphasize the need for first responders to document positioning of unresponsive individuals; and to suggest careful neurological examination and early spinal cord imaging in appropriately identified patients at risk of flexion myelopathy. Case Report: We describe the case of a 34-year-old woman who developed flexion myelopathy resulting in severe quadriparesis after overdose of quetiapine fumarate, oxycodone/acetaminophen, and chloral hydrate. Conclusion: Flexion myelopathy in the setting of drug overdose is a subacute injury. Early intervention may limit neurological disability. However, the clinical diagnosis of flexion myelopathy is inevitably delayed by the patient's altered level of consciousness or mental status at presentation, and concurrent multiple organ failure.     

Nonfatal overdose from alcohol and/or drugs among a sample of recreational drug users

Abstract

The purpose of this study was to examine nonfatal overdose events experienced among a sample of recreational drug users. We sought to determine predictors of nonfatal overdose from alcohol and/or drugs among a sample of recreational drug users. In addition, we examined the substance(s) used at the last overdose event. Methods: Participants were 637 recreational illicit drug users (had used illicit drugs other than marijuana, in a club or party setting), aged 19 or older, from Victoria or Vancouver, British Columbia, Canada. Data were obtained in structured interviews conducted from 2008 to 2012 as part of the Canadian Recreation Drug Use Survey (CRDUS). Results: In the 12 months prior to interview, 19.3% (n?=?123) of the participants had experienced an overdose. In multivariate analysis, younger age, unstable housing, and usually consuming eight or more drinks containing alcohol, when drinking, significantly increased overdose risk. In addition, polysubstance use was reported by 67.5% (n?=?83) participants at their last overdose event. Conclusions: Intervention and prevention measures seeking to reduce overdoses among recreational drug users should not only address illicit drug use but also alcohol and polysubstance use. In addition, measures may target those who usually consume high amounts of alcohol when drinking are younger and who experience housing instability.     

Impact of Chronic Opioid Therapy Risk Reduction Initiatives on Opioid Overdose

We assessed the effects of opioid dose and risk reduction initiatives on opioid overdose rates among patients on chronic opioid therapy (COT). Using an interrupted time series design, we compared trends in overdose rates. We compared patients on COT in settings that implemented a COT dose reduction initiative and then a COT risk stratification/monitoring initiative to similar patients on COT from control settings. From 2006 to 2014, 31,142 patients on COT (22,673 intervention, 8,469 control) experienced 311 fatal or nonfatal opioid overdoses. In primary analyses, changes in opioid overdose rates among patients on COT did not differ significantly between intervention and control settings with the implementation of either dose reduction or risk stratification/monitoring. In planned secondary analyses, overdose rates decreased significantly (17% per year) during the dose reduction initiative among patients on COT in intervention settings (relative annual change, 0.83; 95% confidence interval, 0.70–0.99), but not in control settings (0.98. 95% confidence interval, 0.70–1.39). We conclude that overdose rates among patients on COT were not decreased by risk stratification and monitoring initiatives. Results were inconsistent for COT dose reduction, with no significant difference between intervention and control settings (primary hypothesis test), but a significant decrease in overdose rates within the intervention setting during dose reduction (secondary hypothesis test).

Prevalence of Cardiac Valve Abnormalities in Afebrile Injection Drug Users

OBJECTIVES: To determine the prevalence of occult valvular pathology in afebrile injection drug users (IDUs) compared with an afebrile, non-IDU population. To characterize the type of valvular pathology present in light of current recommendations regarding periprocedural antibiotic prophylaxis against endocarditis. METHODS: This was a comparative, cross-sectional study involving a convenience sample of 98 patients with a history of injection drug use, and 99 non-IDU patients presenting to a large urban ED. Patients were excluded if they had one or more of the following: a history of cardiac valve abnormality, a history of endocarditis, fever on presentation, or a cardiac murmur. Data were collected that included demographics, medical history, and details of injection drug use. Transthoracic echocardiography (echo) was performed on each subject in the ED, and read in a blinded fashion by a single board-certified cardiologist. RESULTS: Among 98 IDUs and 99 non-IDUs, 12% of the IDUs had aortic valve thickening, compared with 5.1% of the non-IDUs (99% CI for difference of 7.8% = -3.0% to 18.6%). Forty-four percent of the IDUs had mitral valve thickening, compared with 25% of the non-IDUs (99% CI for difference of 18.3% = 0.9% to 35.7%). Eleven percent of the IDUs vs 1% of the non-IDUs had tricuspid valve thickening (99% CI for difference of 10.4% = 1.6% to 19.2%). No patient had pulmonic valve thickening. Six percent of the IDUs vs 0% of the non-IDUs had mitral annulus thickening (99% CI for difference of 6.3% = -0.1% to 12.8%). Twelve percent of the IDUs vs 3% of the non-IDUs had mitral chordae thickening (99% CI for difference of 9.5% = -0.4% to 19.4%). Tricuspid chordae thickening was recorded in 2% of the IDUs vs 0% of the non-IDUs (99% CI for difference of 2.1% = -1.7% to 6.0%). Most important, the prevalence of valvular regurgitation was small, and evenly distributed in the two groups. No valvular vegetations were seen. CONCLUSION: Both non-IDUs and IDUs have occult valvular pathology. There is an increased prevalence in IDUs of tricuspid and mitral valve thickening. The prevalence of valvular regurgitation, a reported indication for periprocedural antibiotic prophylaxis, was small and the affected valves were not statistically different between the two groups. These findings question the selected routine use of antibiotic prophylaxis in IDU patients undergoing invasive procedures.     

穴位注射治疗假性延髓麻痹

目的 探讨穴位注射疗法对假性延髓麻痹功能恢复的影响。方法160例假性延髓麻痹患者随机分为2组。治疗组90例采用常规治疗加穴位注射治疗,对照组70例采用常规治疗加针刺治疗。结果 2组治疗后功能均有改善,但治疗组的临床治愈率为87.8%,对照组为52.9%,2组比较,差异有显著性;治疗组疗程明显较对照组短。结论 穴位注射能显著的提高假性延髓麻痹的疗效。     

Toxicology and Overdose of Atypical Antipsychotics

Background

Second-generation antipsychotic medications, or “atypical antipsychotics,” are now first-line therapy in the treatment of schizophrenia and other psychotic disorders, and are additionally being used in a wide array of other psychiatric and non-psychiatric conditions in both adults and children. Overdose is frequently reported to poison control centers.

Objectives

We review the toxicology and general management of poisonings involving the atypical antipsychotic medications.

Discussion

The most serious toxicity involves the cardiovascular system and the central nervous system. All typical and atypical antipsychotics cause sedation, which is pronounced in overdose. The most common cardiovascular effects that occur after atypical antipsychotic overdose are tachycardia, mild hypotension, and prolongation of the QTc interval. Other clinical syndromes in overdose include neuroleptic malignant syndrome (NMS) and antimuscarinic delirium. Seizures may be observed. No antidotes exist for these poisonings, but they most often do well with supportive care.

Conclusion

Antipsychotic overdose produces a gamut of manifestations that affect multiple organ systems. Treatment is primarily supportive. Specific therapies for NMS, hypotension, and seizures are discussed.     

双黄连注射剂不良反应文献评价

目的了解双黄连注射剂不良反应（ADR）在不同年龄、系统和严重程度的分布、构成及影响因素,为双黄连注射剂临床合理应用和上市后再评价提供参考。方法计算机检索中国期刊全文数据库（CNKI,1979.1～2009.9）、中国科技期刊全文数据库（VIP,1989.1～2009.9）和中国生物医学文献数据库（CBM,1978.1～2009.9）,按纳入与排除标准选择文献、提取资料,并按不同类别（年龄、过敏史、涉及系统、联合用药等）计算出双黄连注射剂ADR总数、构成比,根据临床研究中可获得的用药人数与ADR病例数估算ADR发生率。结果①共纳入452篇文献,合计2799例ADR病例,近20年发表文献以病例报告为主（84.51%）,根据69篇文献报告的31165例用药人数和1013例ADR数,计算出ADR总发生率为3.25%。②ADR病例中男女比例为1.13？1,18岁以下未成年人占32.71%。③ADR病例药物过敏史以青霉素最多（占13.38%）,其次为磺胺、头孢菌素、喹诺酮类等。④ADR病例原患疾病中呼吸系统占91.75%,其次为消化系统（5.17%）、泌尿系统（1.11%）等。⑤药物联用以青霉素最多,发生ADR的风险是单用的3.14倍[95%CI（2.58,3.81）]。⑥ADR涉及全身多个系统和器官,构成比由高到低依次为皮肤、消化系统、全身反应、呼吸系统、神经系统、心血管系统、局部反应、泌尿系统、血液系统及其它。⑦按WHO药物ADR严重程度分级,Ⅰ、Ⅱ、Ⅲ、Ⅳ级分别占6.36%、5.48%、45.62%、2.12%;52.42%的ADR病例未描述具体临床表现与转归。⑧12例死亡病例除1例因疼痛诱发心肌梗死致死外,其余均因过敏性休克致死,2例曾合并用药,ADR出现最快者1分钟内。⑨双黄连粉针剂ADR发生率（2.25%）低于注射液（4.14%）,其差异有统计学意义。结论双黄连注射剂ADR临床表现以皮肤过敏和消化道反应为主,联合用药会增加ADR风险,粉针剂比注射液安全性高。建议加强对双黄连注射剂从生产到临床应用过程的监管与监测,严格规范ADR报告,分级风险评估与管理ADR。     

944篇521例刺五加注射液不良反应文献分析

目的全面了解刺五加注射液不良反应（adverse drug reactions,ADR）发生情况及其相关因素。方法检索中国知网（CNKI）关于刺五加注射液的临床研究及不良反应报告。提取纳入文献中ADR病例原患疾病,刺五加注射液用药剂量、溶媒及配伍用药情况,ADR病例的性别、年龄及有无过敏史情况,ADR出现时间、类型、处理及转归等。结果800篇临床研究中有97篇（12.1%）共报道285例ADR病例;144篇ADR报告共包括236例ADR病例。ADR病例中女性高于男性,主要集中于40～69岁年龄段;不良反应报告的ADR主要集中于过敏性休克,临床研究的ADR主要集中于注射局部疼痛;72.3%的ADR病例严重程度为Ⅲ～Ⅳ级,4例死亡;ADR病例原患疾病最主要为冠心病和脑梗死;27例（11.4%）ADR病例有过敏史;刺五加注射液ADR病例所用溶媒主要为5%葡萄糖液、生理盐水和10%葡萄糖液,共36例ADR病例为刺五加注射液和其他药物配伍使用;刺五加注射液常用剂量为20～60ml;首次用药者ADR病例占总ADR的83.0%。结论①刺五加注射液的ADR报告和临床研究均存在ADR/AE（不良事件）概念模糊,关键信息不完整,缺乏总处方量/用药人数,及不能计算发生率的缺陷,报告质量尚待提高。②刺五加注射液的基础研究有待深入,特别是剂量探索研究,以支持临床应用。③刺五加作为ADR报告最多的中药注射剂品种之一,统一规划下的高质量ADR监测、规范报告和及时析因、指导改进迫在眉睫。     

Drug Overdose,Loss of Consciousness,and Compartment Syndrome: A Life-Threatening Combination

Acute extremity compartment syndrome is considered an orthopedic emergency that has serious consequences if a correct diagnosis is not made rapidly. Patients who lose consciousness due to a drug overdose are known to collapse onto their extremities. The limbs are compressed for hours, placing them at an increased risk for acute extremity compartment syndrome and its sequelae. Compartment syndrome due to a compression of a limb from loss of consciousness secondary to drug overdose, presents unique issues to health care providers. In the setting of overdose compartment syndrome, it is similar to the more common traumatic type of compartment syndrome with respect to the pathophysiology, diagnosis and treatment. However, it differs in relation to the muscles affected, physical assessment strategy, and accurately determining the amount of the time from onset of injury to the presentation of symptoms. The purpose of this article is to facilitate emergency department nurses' understanding of the complexities of overdose compartment syndrome, combined with the importance of early recognition of the condition. In addition, the authors review the pathophysiology, the traditional and innovative diagnostic techniques, and the current treatment options available for overdose compartment syndrome.     

Out-of-hospital Care of Critical Drug Overdoses Involving Cardiac Arrest

OBJECTIVES: Death from acute drug poisoning, also termed drug overdose, is a substantial public health problem. Little is known regarding the role of emergency medical services (EMS) in critical drug poisonings. This study investigates the involvement and potential mortality benefit of EMS for critical drug poisonings, characterized by cardiovascular collapse requiring cardiopulmonary resuscitation (CPR). METHODS: The study population was composed of death events caused by acute drug poisoning, defined as poisoning deaths and deaths averted (persons successfully resuscitated from out-of-hospital cardiac arrest by EMS) in King County, Washington, during the year 2000. RESULTS: Eleven persons were successfully resuscitated and 234 persons died from cardiac arrest caused by acute drug poisoning, for a total of 245 cardiac events. The EMS responded to 79.6% (195/245), attempted resuscitation in 34.7% (85/245), and successfully resuscitated 4.5% (11/245) of all events. Among the 85 persons for whom EMS attempted resuscitation, opioids, cocaine, and alcohol were the predominant drugs involved, although over half involved multiple drug classes. Among the 11 persons successfully resuscitated, return of circulation was achieved in six following EMS cardiopulmonary resuscitation alone, in one following CPR and defibrillation, and in the remaining four after additional advanced life support. CONCLUSIONS: In this community, EMS was involved in the majority of acute drug poisonings characterized by cardiovascular collapse and may potentially lower total mortality by approximately 4.5%. The results show that, in some survivors, return of spontaneous circulation may be achieved with CPR alone, suggesting a different pathophysiology in drug poisoning compared with cardiac arrest due to heart disease.     

Endoscopic Removal of Pharmacobezoar in Case of Intentional Potassium Overdose

Background

Hyperkalemia is a potentially life-threatening electrolyte abnormality commonly seen in the emergency department (ED). Intentional overdose of potassium supplements is an uncommon occurrence.

Objective

This case illustrates a novel approach to treatment of pharmacobezoar with esophagogastroduodenoscopy (EGD) and demonstrates its effectiveness in the setting of extended-release potassium chloride overdose.

Case Report

A 44-year-old female presented to the ED with intentional ingestion of an unknown amount of extended-release potassium chloride (K-Dur®) tablets and alprazolam (Xanax®). The patient's serum potassium was initially 7.3 mmol/L and she was treated with standard treatments, including albuterol, calcium gluconate, insulin, dextrose, and sodium bicarbonate. Radiographic investigation showed a pharmacobezoar in the gastric fundus. Treatment was then augmented with whole bowel irrigation (WBI) using polyethylene glycol solution via nasogastric tube. Patient did not tolerate the nasogastric tube, became combative with increasing alteration in her level of consciousness, and WBI therapy was stopped. After discussion with the gastroenterologist, the patient was treated with EGD to remove the pharmacobezoar. The EGD was successful in the removal of the pharmacobezoar and the patient's potassium normalized without complications.

Conclusions

We recommend that in cases of suspected or confirmed potassium drug bezoar in the stomach, physicians consider EGD for removal. This allows for normalization of potassium level while preventing adverse sequelae.     

Endotracheal Intubation after Acute Drug Overdoses: Incidence,Complications, and Risk Factors

Background

Drug overdose is the leading cause of injury-related fatality in the United States, and respiratory failure remains a major source of morbidity and mortality.

Management of Ventricular Dysrhythmia Secondary to Trazodone Overdose

Torsades de pointes (TdP), a life-threatening ventricular dysrhythmia, was recorded in a 30-year-old woman who had taken a deliberate overdose of trazodone. The patient was successfully defibrillated to normal sinus rhythm and given intravenous magnesium sulfate according to Advanced Cardiovascular Life Support guidelines. The patient was discharged and experienced no further complications.     

Feasibility of Bystander Administration of Public-Access Naloxone for Opioid Overdose

Objective: Pre-stationing naloxone, a competitive antagonist that can reverse the effects of opioid overdose, in public spaces may expedite antidote delivery. Our study aimed to determine the feasibility of bystander-assisted overdose treatment using pre-stationed naloxone. Methods: Convenience sample of bystanders in Cambridge, Massachusetts in April 2017. Subjects assisted a simulated patient described as unconscious. Subjects interacted with simulated EMS dispatch to locate a nearby box, unlock it, and administer naloxone. Results: Fifty participants completed the simulation. Median time from simulated ambulance dispatch to naloxone administration was 189 seconds, and from arrival at patient side to administration 61 seconds. All but one participant (98.0%) correctly administered naloxone. Subjects' comfort with administration and willingness to provide medical care increased from before to after the trial. Comfort in administering naloxone varied significantly with level of previous training prior to, but not following, study participation. Conclusions: Bystanders are willing and able to access pre-stationed naloxone and administer it to a simulated patient in a public space. Public access naloxone stations may be a useful tool to reduce time to naloxone administration, particularly in areas where opioid overdoses are clustered.     

胃镜下硬化剂注射联合药物治疗食管静脉曲张出血

目的：观察比较胃镜下硬化剂注射联合药物治疗和单纯硬化剂注射治疗、药物治疗食管静脉曲张出血的疗效。方法：95例肝硬化并食管静脉曲张出血患者,分成三组。32例患者给予硬化剂注射联合药物治疗,31例患者给予硬化剂治疗,32例患者给予药物治疗。观察三组患者急诊止血率,近期出血率、远期再出血率、曲张静脉消失率、曲张静脉复发率。结果：联合组、硬化剂组、药物组急诊止血率分别为93.8%、90.3%、68.8%;联合组、硬化剂组、药物组近期出血率分别为6.3%、9.7%、46.9%;联合组、硬化剂组、药物组曲张静脉消失率分别为90.6%、83.9%、1.9%;联合组、硬化组与药物组急诊止血率、近期出血率、曲张静脉消失率有显著差异。联合组、硬化剂组、药物组远期出血率分别为9.4%、59.4%、31.3%;联合组、硬化剂组、药物组曲张静脉复发率分别为18.8%、45.2%、87.5%;联合组与硬化组、药物组远期出血率、曲张静脉复发率有显著差异。结论：胃镜下硬化剂注射联合药物治疗食管静脉曲张出血可显著提高疗效。     

Pharmacokinetic Effects of Diphenhydramine or Oxycodone in Simulated Acetaminophen Overdose

Objectives: To determine the effects of co‐ingested diphenhydramine (DPH) or oxycodone (OXY) on the absorption kinetics of simulated acetaminophen (APAP) overdose. Methods: This was an institutional review board–approved, prospective crossover study of ten healthy human volunteers ingesting 5 grams of APAP, 5 grams of APAP + 250 mg of DPH (APAP+DPH), or 5 grams of APAP + 0.5 mg/kg of OXY (APAP+OXY). Serum APAP concentrations (APAPs) were measured hourly from zero through eight hours and again at 24 hours, and basic noncompartmental pharmacokinetic parameters were compared. Results: For APAP alone, the mean parameters were: maximum APAP concentration ([APAP]_max) 71.8 μg/mL, time to peak [APAP] (t_max) 1.71 hours, and area under the receiver operating characteristic curve (AUC_0–8) 318.3 μg‐hr/mL. For APAP+DPH, the mean parameters were: [APAP]_max 67.6 μg/mL, t_max 1.90 hours, and AUC_0–8 297.7 μg‐hr/mL. For APAP+OXY, the parameters were: [APAP]_max 42.9 μg/mL, t_max 2.87 hours, and AUC_0–8 232.1 μg‐hr/mL. Compared with APAP alone, APAP+OXY had a 27% lower AUC, a 40% lower [APAP]_max, and a 68% longer t_max. Co‐ingested DPH had no significant effect on APAP absorption, except a 6% decrease in the AUC. Conclusions: Co‐ingested OXY, but not DPH, delayed absorption of APAP. This suggests a potential role for activated charcoal administration beyond one hour postingestion after mixed ingestions that include OXY.     

海洛英中毒并急性肺水肿的特点和救治

目的：探讨海洛因中毒并急性肺水肿的临床特点及有效抢救方法。方法：回顾性分析我院自1990～2003年收治的15例海洛因中毒并急性肺水肿临床资料。结果：15例患者均以昏迷、呼吸抑制、针尖样瞳孔以及双肺布满湿罗音为主要特征，血气分析呈低氧血症、高碳酸血症和酸中毒，胸片显示急性肺水肿改变，经通气，使用纳络酮等综合治疗后，抢救成功13例，占86．6％，死亡占13．4％。结论：海洛因中毒并急性肺水肿，病情凶险，进展迅速，但经恰当治疗，病情是可逆的；早期、足量、持续使用纳络酮是抢救成功的关键。     

静脉用药具与压力对药液微粒污染的实验观察

目的 探讨注射器具和压力对静脉用药中药液微粒污染的影响及对策。方法 用ZWF－4型注射液微粒分析仪检测静脉滴静脉推注的器具及加压后药液中不溶性微粒的数目。结果 一次性注射器及头皮针对药液微粒污染的影响无显著差异；一次性输液三通管在未加压的情况下有滞留药液微粒的作用，加压后微粒显著增加。结论 应重视静脉用药时压力对药液微粒污染的影响，尤其是静脉滴注联合静脉推注药液的病人，静脉推注药液应加过滤装置，以提高用药的安全性。