Predictors of non-fatal overdose among a cohort of polysubstance-using injection drug users

BACKGROUND: Non-fatal overdose is a major determinant of morbidity among injection drug users (IDU). We sought to evaluate factors associated with non-fatal overdose among IDU in Vancouver. METHODS: We examined non-fatal overdose among participants in the Vancouver Injection Drug Users Study. Correlates of non-fatal overdose occurring between 1996 and 2004 were identified using generalized estimating equations (GEE). RESULTS: There were 1587 participants included in this analysis, including 576 (36%) women. At baseline, 750 (47%) reported a history of non-fatal overdose. In total, 985 reports of non-fatal overdose were made during follow-up by 519 (32.7%) participants. In multivariate GEE analyses, factors independently associated with non-fatal overdose included: heroin injection (AOR=2.67), cocaine injection (AOR=2.01), benzodiazepine use (AOR=2.00), requiring help injecting (AOR=1.58), binge drug use (AOR=1.52), homelessness (AOR=1.38), alcohol use (AOR=1.32), street injecting (AOR=1.22), non-injectable opiate use (AOR=1.16), speedball use (AOR=1.15), and recent incarceration (AOR=1.14). Younger age (AOR=0.99) and methadone use (AOR=0.51) were protective. CONCLUSIONS: We found that non-fatal overdose was common among local IDU. Non-fatal overdose was associated with several factors that may be amenable to intervention, including opiate and stimulant use, and the characteristic of requiring help with injecting. These findings indicate the need for the ongoing development of structural interventions to address this common cause of morbidity among IDU.     

The pharmacokinetics of sertraline in overdose and the effect of activated charcoal

Aims

To investigate the pharmacokinetics (PK) of sertraline in overdose and the effect of single dose activated charcoal (SDAC).

Methods

Patients presenting to a toxicology unit with sertraline overdoses had demographic and clinical information recorded, and serial serum collected for measurement of sertraline concentrations. Monolix® version 4.2 was used to develop a population PK model of sertraline overdose and the effect of SDAC. Uncertainty in dose time was accounted for by shifting dose time using lag time with between subject variability (BSV). BSV on relative fraction absorbed was used to model uncertainty in dose.

Results

There were 77 timed sertraline concentrations measured in 28 patients with sertraline overdoses with a median dose of 1550 mg (250–5000 mg). SDAC was given to seven patients between 1.5 and 4 h post-overdose. A one compartment model with lag time of 1 h and first order input and elimination adequately described the data. Including BSV on both lag time and relative fraction absorbed improved the model. The population PK parameter estimates for absorption rate constant, volume of distribution and clearance were 0.895 h⁻¹, 5340 l and 130 l h⁻¹, respectively. The calculated half-life of sertraline following overdose was 28 h (IQR 19.4−30.6h). When given up to 4 h post-overdose, SDAC significantly increased the clearance of sertraline by a factor of 1.9, decreased the area under the curve and decreased the maximum plasma concentration (C_max).

Conclusions

Sertraline had linear kinetics in overdose with parameter values similar to those in therapeutic use. SDAC is effective in increasing clearance when given 1.5 to 4 h post-overdose.     

264张处方有毒中药饮片超剂量使用分析

目的：调查门诊中药饮片处方中有毒中药饮片超剂量使用情况,为中医临床合理用药提供参考。方法：随机抽取2016年6月至2017年5月门诊中药饮片处方,参照《中国药典》（2015年版）和《上海市中药饮片炮制规范》（2008年版）规定的中药饮片用量范围,对处方中超剂量使用的有毒中药饮片的品种、剂量、各剂量使用频次和频率、超剂量程度等进行统计分析。结果：超剂量使用的有毒中药饮片共有21个品种,占某院有毒中药饮片品种数的45.65%,其中12种有两种以上超上限使用剂量;超剂量使用频率排名前五位的中药饮片品种和剂量分别是水蛭9 g、吴茱萸6 g、蒺藜15 g、仙茅12 g、天仙子9 g;超剂量使用程度排序,水蛭12 g位列第一,是剂量上限的4倍。小毒中药饮片较有毒中药饮片平均超剂量使用频率更高,但两者平均超剂量使用程度并无显著性差异（P>0.05）。活血化瘀药和平肝息风药的超剂量使用频率和程度均排名前三。结论：有毒中药饮片超剂量使用整体情况较合理。建议结合地区用药习惯,制定中药饮片尤其是有毒中药饮片的剂量范围,以保证临床用药安全、有效。     

Intravenous acetylcysteine for the treatment of acetaminophen overdose

Importance of the field: Acetaminophen is a leading cause of overdose-related hepatotoxicity. Although acetylcysteine prevents or minimizes acetaminophen-induced hepatotoxicity and reduces mortality, some patients presenting with complicated overdose scenarios (massive ingestions or combination or modified-release formulations) may develop toxicity despite administration of recommended dosage regimen.

Areas covered in this review: The article evaluates evidence regarding intravenous acetylcysteine's effectiveness in patients with acute overdoses who receive treatment within 10 h or > 10 h, patients with chronic supratherapeutic ingestions, and those with acetaminophen-induced fulminant hepatic failure. Intravenous and oral acetylcysteine are compared.

What the reader will gain: A one-size-fits-all approach towards acetylcysteine therapy provides suboptimal care in some patients. High-risk patients are identified. Specific discontinuation criteria are presented.

Take home message: The standard intravenous regimen will effectively treat most early-presenting uncomplicated overdoses. Acetylcysteine dosing should be individualized in patients with complicated presentations and in particular situations in which plasma acetaminophen concentrations may be persistently elevated at the end of the infusion or in late presenters. More studies are needed to evaluate the optimal intravenous dosage regimen and the role of oral acetylcysteine in these high-risk patients. Treatment decisions may be aided by consultation with a poison center and/or clinical toxicologist.     

丙戊酸钠和丙戊酸镁在大鼠体内的药动学研究

目的 研究丙戊酸钠和丙戊酸镁在大鼠体内的药动学特征,评价其优势丙戊酸盐,为临床合理用药提供参考。方法 SD大鼠随机分为2组,分别灌胃给予丙戊酸钠片和丙戊酸镁片。于不同时间点眼眶取血。采用HPLC测定血清中丙戊酸的血药浓度,计算2种丙戊酸盐在大鼠体内的药动学参数,并比较2种丙戊酸盐之间的差异。结果 HPLC测定丙戊酸血药浓度方法专属性好,血清丙戊酸浓度在10.00~110.00 μg·mL^-1内线性关系良好。精密度、稳定性和回收率均符合要求。丙戊酸钠和丙戊酸镁在大鼠体内的主要药动学参数：T_1/2分别为（14.02±3.86） h和（12.11±1.95） h;T_max分别为（3.67±0.58） h和（2.67±0.26） h;C_max分别为（67.10±10.87）μg·mL^-1和（75.67±12.94）μg·mL^-1;AUC_（0-t）分别为（969.86±72.08）μg·mL^-1·h和（1 093.56±48.69）μg·mL^-1·h;AUC_（0-∞）分别为（1 178.10±185.29）μg·mL^-1·h和（1 279.35±109.18）μg·mL^-1·h;MRT_0-t分别为（10.73±2.05） h和（13.06±3.24） h。V_d分别为（16.31±2.18） L和（23.47±2.19） L;CL分别为（0.056 3±0.009） L·h^-1和（0.051 1±0.004） L·h^-1。结论 与丙戊酸钠相比,丙戊酸镁在大鼠体内的药动学参数具有一定的优势,可能是一种更具有治疗优势的丙戊酸盐。     

Suicidal antidepressant overdoses: A comparative analysis by antidepressant type

Introduction

The safety of antidepressants following overdose is critical because of the high risk of suicide attempts in depressed patients. This study was conducted to decrease the fatality rate of antidepressant overdoses by providing data to shift prescribing toward safer antidepressants.

Methods

US poison control data for 2000–2004 were analyzed by 25 antidepressant types. Medical outcome differences were quantified using a hazard index (number of major or fatal outcomes per 1000 reported antidepressant ingestions).

Results

Of 82,802 suicidal single-agent ingestions of identifiable antidepressants approved for use in the US, cases occurred predominantly in females and peaked in teens. Fatal cases peaked at 40 to 49 years of age. Suicidal ingestions of the SSRIs, SNRIs, and other antidepressants peaked in teens, lithium in the twenties, tricyclics and tetracyclics in the thirties, and MAO inhibitors in the forties. There were 40 major or fatal outcomes per 1000 cases. Weighted by antidepressant type, the mean hazard index for the 25 antidepressants was 79 (range: 0 to 292). Amoxapine (292), maprotiline (211), and desipramine (187) had the highest hazard indices. The tricyclic antidepressants, MAO inhibitors, maprotiline, and bupropion were in the more severe half of antidepressants, ranked by hazard index. All SSRIs had low hazard indices. Hazard index and exposure frequency were inversely correlated (R = −0.423, p = 0.035), while hazard index and use of critical care were positively correlated for the 25 antidepressant types (R = 0.797, p < 0.001). Clinical effect profiles for each antidepressant type are presented.

Conclusion

Suicidal overdose severity varied considerably by antidepressant type. Prescribing decisions should be informed by regularly updated comparative overdose severity data.     

Extracorporeal treatments in poisonings from four non‐traditionally dialysed toxins (acetaminophen,digoxin, opioids and tricyclic antidepressants): A combined single‐centre and national study

The use of extracorporeal treatments (ECTRs) for poisonings with four non‐traditionally dialysed toxins (NTDTs) is increasing in the United States. This study evaluated whether ECTRs are prescribed for toxin removal or the treatment of other medical illnesses or complications. We performed a 2‐Phase retrospective analysis evaluating the main indication for ECTRs in patients with poisoning from a NTDT (defined for this study as acetaminophen, opioids, tricyclic antidepressants (TCAs) or digoxin) and ECTR. The first phase assessed all cases from a single site (New York City Poison Control Center) between the years 2000 and 2016, and the second phase surveyed all United States Poison Control Centers (PCCs). In Phase 1, demographics, toxin ingested and main indication for ECTR were extracted. In Phase 2, a query to the National Poison Data System using the a pragmatic subset of inclusion criteria from Phase 1 restricted to single toxin ingestions over a narrower time frame (2014‐2016) provided the cases for study. A structured online questionnaire was sent to all United States PCCs to request their database review regarding the indication for ECTR for their cases. In Phase 1, 92 cases met inclusion criteria. In Phase 2, 519 cases were screened and 425 met inclusion criteria. In Phase 1 91/92 (98.9%) and Phase 2 411/425 (96.7%), of extracorporeal treatments were used to treat underlying medical conditions or poisoning‐related complications rather than accelerate toxin removal. The increasing number of ECTRs reported in patients who ingested one of the four NTDTs thus appears to be for medical indications rather than attempts at toxin removal, a distinction that is important.     

Emergency department presentation and mortality rate due to overdose: A retrospective cohort study on nonfatal overdoses

ABSTRACT

Background: The aims of this retrospective cohort study are to describe the presentation characteristics for nonfatal overdose-related complaints at the emergency departments (EDs) of the metropolitan area of Bologna (northern Italy), to estimate the subsequent risk of mortality by overdose, and to identify the profiles of the subjects most at risk. Methods: Records of patients admitted to 10 EDs for overdose between January 2004 and December 2012 were retrospectively evaluated. The International Classification of Diseases was used to ascertain the cause of death. Results: A total of 294 episodes of overdose involving 218 individuals were identified. The total time at risk was 1048 person-years (PY). The mortality rate for all causes was 35.48 per 1000 PY for males and 20.61 per 1000 PY for females. The mortality rate for overdose was 16.6 per 1000 PY for males and 13.74 per 1000 PY for females. In the multivariate regression analysis, the time from first ED overdose access (less than 1 year risk ratio [RR]: 7.07, 95% confidence interval [CI]: 5.32–9.39) was significantly associated with death by overdose. Males, subjects aged >30 years at presentation, patients who refused ED treatment, and those having previously contacted mental health services showed an increased mortality risk due to overdose. Conclusions: Experiencing a nonfatal overdose within the past 12 months increases the risk of mortality compared with an overdose more than 12 months earlier. Nonfatal overdose patients presenting to an ED form a specific target for prevention projects.     

Fatality related to a 30-g venlafaxine overdose

A 30-g venlafaxine overdose resulted in death for a 39-year-old woman whose 43-day clinical course was highlighted by refractory hypotension and the resulting complications of bowel ischemia and perforation. Her venlafaxine and O-desmethylvenlafaxine levels, analyzed by high-performance liquid chromatography one day after ingestion, were 21.82 mg/L (therapeutic range 0.1-0.5 mg/L) and 3.33 mg/L (0.2-0.4 mg/L), respectively. These levels remained elevated for over 7 days. Postulated explanations for these extended elevated levels were saturation of drug metabolism, decreased drug metabolism, and existence of a genetic polymorphism. Our patient's venlafaxine overdose produced a wide variety of clinical challenges, to include seizures, tachycardia, decreased level of consciousness, refractory hypotension, and bowel dysmotility. In addition, this case augments the growing body of literature that suggests that venlafaxine may be fatal in overdose situations.     

Opioid overdose prevention in a residential care setting: Naloxone education and distribution

Background: Patients with opioid use disorders are at an increased risk for overdose death if they had a previous overdose, have co-occurring medical and psychiatric comorbidity, and are high-dose opioid users transitioning to relative abstinence or abstinence, i.e., those individuals discharging from drug treatment programs. Despite the success of opioid overdose prevention programs utilizing naloxone, residential substance abuse treatment centers often emphasize abstinence-based care for those suffering from addiction and do not adopt harm reduction approaches such as naloxone education and distribution. This performance improvement project reports the implementation of an opioid overdose prevention program provided to patients and their family members in a residential treatment setting. Methods: Opioid-dependent inpatients (N = 47) along with their family members received overdose prevention training consistent with guidelines established by the Harm Reduction Coalition. Patient family members were queried regarding their awareness of past opioid overdose by the patient. A pre- and post-training questionnaire based on a 5-point Likert scale assessing ability to recognize overdose, fear of overdose, comfort in assisting with overdose, perception of life-threatening nature of addiction, and the value of overdose management was administered. Pre and post scores for each Likert scale were analyzed using paired 2-tailed t tests. Results: Thirty-two percent of patient family members were aware that the patient had a prior overdose. Statistically significant improvements in the ability of patients and families to recognize an opioid overdose as well as in their comfort to assist with an overdose were demonstrated. The pre- and post-education responses were both notably high for perceived value in learning about overdose and prevention. Conclusions: Implementation of opioid overdose prevention programs within residential treatment programs, sober living homes, and therapeutic communities would be well received and is strongly encouraged.     

An evaluation of a heroin overdose prevention and education campaign

Introduction and Aims. Following detection of an upward trend in the frequency of fatal heroin overdoses in Victoria between 2001 and 2003, Victoria's Department of Human Services planned a campaign aimed at increasing injecting drug users' (IDU) awareness of overdose risks and prevention strategies. Stickers, wallet cards and posters featuring five key messages were distributed via needle and syringe programs (NSP) and other drug and alcohol services between November 2005 and April 2006. An evaluation of the campaign was commissioned to be conducted in late 2006. Design and Methods. The evaluation consisted of analysis of three independent data sets––quantitative data collected from IDU during the campaign period (n = 855 at baseline; and a range of 146–656 at follow up); qualitative interviews with IDU who were NSP clients during the campaign period (n = 16) and qualitative interviews with NSP staff and other key stakeholders (n = 9). Results. While key experts felt that the campaign messages had engendered lasting impact for at least some IDU, these positive impressions were not borne out by the NSP client data, with less than one quarter of all campaign messages being mentioned by a significantly higher proportion of clients during the post‐campaign period compared with baseline. Key experts perceived the greatest weakness of the campaign to be the delay between issue identification and the introduction of campaign materials. Discussion and Conclusions. While IDU are generally responsive to health promotion campaigns, future initiatives in this domain should be designed and implemented rapidly and in ways that are sufficiently flexible to cope with shifts in drug markets which could influence the reception of key messages.[Horyniak D, Higgs P, Lewis J, Winter R, Dietze P, Aitken C. An evaluation of a heroin overdose prevention and education campaign. Drug Alcohol Rev 2009]     

Use of online opioid overdose prevention training for first-year medical students: A comparative analysis of online versus in-person training

Purpose: In response to the opioid epidemic and efforts to expand substance use education in medical school, the authors introduced opioid overdose prevention training (OOPT) with naloxone for all first-year medical students (MS1s) as an adjunct to required basic life support training (BLST). The authors previously demonstrated improved knowledge and preparedness following in-person OOPT with BLST; however, it remains unclear whether online-administered OOPT would produce comparable results. In this study, the authors perform a retrospective comparison of online-administered OOPT with in-person-administered OOPT. Objectives: To compare the educational outcomes: knowledge, preparedness, and attitudes, for online versus in-person OOPT. Methods: In-person OOPT was administered in 2014 and 2015 during BLST, whereas online OOPT was administered in 2016 during BLST pre-work. MS1s completed pre- and post-training tests covering 3 measures: knowledge (11-point scale), attitudes (66-point scale), and preparedness (60-point scale) to respond to an opioid overdose. Online scores from 2016 and in-person scores from 2015 were compared across all 3 measures using analysis of covariance (ANCOVA) methods. Results: After controlling for pre-test scores, there were statistical, but no meaningful, differences across all measures for in-person- and online-administered training. The estimated differences were knowledge: ?0.05 (0.5%) points (95% confidence interval [CI]: ?0.47, 0.36); attitudes: 0.65 (1.0%) points (95% CI: ?0.22, 1.51); and preparedness: 2.16 (3.6%) points (95% CI: 1.04, 3.28). Conclusions: The educational outcomes of online-administered OOPT compared with in-person-administered OOPT were not meaningfully different. These results support the use of online-administered OOPT. As our study was retrospective, based on data collected over multiple years, further investigation is needed in a randomized controlled setting, to better understand the educational differences of in-person and online training. Further expanding OOPT to populations beyond medical students would further improve generalizability.     

Bereavement following a fatal overdose: The experiences of adults in England and Scotland

Abstract

Aims: Overdoses contribute disproportionately to drug-related deaths (DRDs) in the UK, yet little is known about the experiences and needs of those who are bereaved by such deaths, and how their experiences and needs might differ from other bereavements associated with substance use. Methods: An interview study with 32 adults in England and Scotland (part of a larger study). Findings: Five themes describe the core experiences of this group of bereaved people: drug use, the death, official processes, stigma, and overdose awareness and prevention. Together, these findings offer new insights in to the key features of this type of bereavement; for example, living with substance use including previous overdoses, difficult circumstances surrounding the death, having to negotiate the complex procedures involved in processing the death, the stigma such deaths attract, and feelings of guilt, self-blame and an unworthiness to grieve. Conclusions: There are ways in which bereavement following an overdose differs from bereavement following other deaths associated with alcohol or drugs. Understanding the experiences and needs of this marginalised group can help improve support for them. Furthermore, this group’s experience of witnessing and/or responding to previous overdoses indicates the value in prevention programmes targeting relatives/friends.