Differentiating Ischemic Hepatitis from Acetaminophen Overdose in Acute Liver Failure: Role of Acetaminophen Adducts-Ischemic Hepatitis vs Acetaminophen Overdose.

BACKGROUND AND AIMS: Acetaminophen (APAP) hepatotoxicity and ischemic hepatic injury (IH) demonstrate remarkably similar biochemical patterns. Deciding between these two etiologies in the setting of acute liver failure (ALF) can be challenging. We reviewed all cases in the Acute Liver Failure Study Group (ALFSG) registry where these diagnoses were considered, to determine reasons for, and frequency of, difficulties making these diagnoses. We hypothesized that the newly developed APAP-CYS adduct assay could help in discerning the correct diagnosis. METHODS: Among 3364 patients with ALF or acute liver injury (ALI: INR ≥ 2.0 but without encephalopathy) between 1998 and 2019, 1952 (58%) received a final diagnosis of either APAP (1681) or IH (271). We utilized a review committee of senior hepatologists as well as the APAP-CYS assay (where sera were available), measuring the presence of toxic by-products of APAP injury to optimize adjudication. RESULTS: With these methods, a total of 575 adduct positive APAP cases included 488 recognized APAP, as well as an additional 87 patients previously diagnosed as other etiologies. Nine cases initially attributed to IH were deemed combination APAP-IH injuries. Conversely, 215 of the 280 IH subjects tested for adducts disclosed 173 confirmed as IH with adduct testing below the toxicity threshold, while 9 cases were revised from APAP to the IH-APAP combination phenotype, where both hypotension and APAP likely played a role. CONCLUSIONS: Discerning APAP from IH can be difficult-in rare cases, combined injury is observed (18/1952). APAP-CYS testing resulted in revising the diagnosis in 14.6% of cases.

Chronic pain and accidental acute toxicity deaths in Canada, 2016-2017. / Recherche quantitative originale La douleur chronique et les décès par intoxication aiguë accidentelle au Canada, 2016-2017.

INTRODUCTION: Multiple Canadian jurisdictions have reported a pattern of chronic pain among people who died from substance-related acute toxicity. This study examined the prevalence and characteristics of those with chronic pain using data from a national study of people who died of accidental acute toxicity. METHODS: A cross-sectional analysis of accidental substance-related acute toxicity deaths that occurred in Canada between 1 January 2016 and 31 December 2017 was conducted. The prevalence of pain and pain-related conditions were summarized as counts and percentages of the overall sample. Subgroups of people with and without a documented history of chronic pain were compared across sociodemographic characteristics, health history, contextual factors and substances involved. RESULTS: From the overall sample (n = 7902), 1056 (13%) people had a history of chronic pain while 6366 (81%) had no documented history. Those with chronic pain tended to be older (40 years and older), unemployed, retired and/or receiving disability supports around the time of death. History of mental health conditions, trauma and surgery or injury was significantly more prevalent among people with chronic pain. Of the substances that most frequently contributed to death, opioids typically prescribed for pain (hydromorphone and oxycodone) were detected in toxicology more often among those with chronic pain than those without. CONCLUSION: Findings underscore the cross-cutting role of multiple comorbidities and unmanaged pain, which could compound the risk of acute toxicity death. Continued prioritization of harm reduction and regular patient engagement to assess ongoing needs are among the various opportunities for intervention.

Pharmacobezoar Associated Prolonged Clinical Course in a Patient with Immediate Release Quetiapine Overdose.

INTRODUCTION: Quetiapine is available in both immediate-release (IR) and extended-release (XR) formulations. Quetiapine XR overdose is known to cause delayed increase in serum quetiapine concentrations. However, it is not certain whether quetiapine IR overdose would similarly cause a delayed increase in serum quetiapine concentrations. CASE REPORT: A 57-year-old woman with depression who was taking half a tablet of 25 mg quetiapine IR daily was transported to our emergency department with a complaint of disturbance of consciousness 12 h after a quetiapine IR overdose. On arrival, her initial vital signs were heart rate of 116 beats per minute, blood pressure of 77/43 mm Hg, and oxygen saturation of 91% under 10 L oxygen administration. Whole body plain computed tomography showed a large amount of gastric hyperdense content suggesting pharmacobezoar with a volume of 71.2 ml. After treatment with respiratory and circulatory support, gastric lavage was performed. Her disturbance of consciousness persisted until day 5, and she was extubated on day 7. The serum concentrations of quetiapine were 2690 ng/mL at 12 h after overdose, 5940 ng/mL at 40 h, and 350 ng/mL at 124 h after overdose. Serum concentrations of other co-ingestions were all below lethal levels. CONCLUSION: A massive quetiapine IR overdose with pharmacobezoars can cause a delayed increase in serum quetiapine concentrations.

Reported Xylazine Use Among Adults Aged ≥18 Years Evaluated for Substance Use Treatment - United States, July 2022-September 2023.

Xylazine has been increasingly detected in illegally manufactured fentanyl (IMF) products and overdose deaths in the United States; most xylazine-involved overdose deaths involve IMF. A convenience sample of U.S. adults aged ≥18 years was identified from those evaluated for substance use treatment during July 2022-September 2023. Data were collected using the Addiction Severity Index-Multimedia Version clinical assessment tool. Among 43,947 adults, 6,415 (14.6%) reported IMF or heroin as their primary lifetime substance-use problem; 5,344 (12.2%) reported recent (i.e., past-30-day) IMF or heroin use. Among adults reporting IMF or heroin as their primary lifetime substance-use problem, 817 (12.7%) reported ever using xylazine. Among adults reporting recent IMF or heroin use, 443 (8.3%) reported recent xylazine use. Among adults reporting IMF or heroin use recently or as their primary lifetime substance-use problem, those reporting xylazine use reported a median of two past nonfatal overdoses from any drug compared with a median of one overdose among those who did not report xylazine use; as well, higher percentages of persons who reported xylazine use reported other recent substance use and polysubstance use. Provision of nonjudgmental care and services, including naloxone, wound care, and linkage to and retention of persons in effective substance use treatment, might reduce harms including overdose among persons reporting xylazine use.

Mobile addiction treatment and harm reduction services as tools to address health inequities: a community case study of the Brockton Neighborhood Health Center mobile unit.

Opioid overdose deaths continue to increase in the US. Recent data show disproportionately high and increasing overdose death rates among Black, Latine, and Indigenous individuals, and people experiencing homelessness. Medications for opioid use disorder (MOUD) can be lifesaving; however, only a fraction of eligible individuals receive them. Our goal was to describe our experience promoting equitable MOUD access using a mobile delivery model. We implemented a mobile MOUD unit aiming to improve equitable access in Brockton, a racially diverse, medium-sized city in Massachusetts. Brockton has a relatively high opioid overdose death rate with increasingly disproportionate death rates among Black residents. Brockton Neighborhood Health Center (BNHC), a community health center, provides brick-and-mortar MOUD access. Through the Communities That HEAL intervention as part of the HEALing Communities Study (HCS), Brockton convened a community coalition with the aim of selecting evidence-based practices to decrease overdose deaths. BNHC leadership and coalition members recognized that traditional brick-and-mortar treatment locations were inaccessible to marginalized populations, and that a mobile program could increase MOUD access. In September 2021, with support from the HCS coalition, BNHC launched its mobile initiative - Community Care-in-Reach® - to bring low-threshold buprenorphine, harm reduction, and preventive care to high-risk populations. During implementation, the team encountered several challenges including: securing local buy-in; navigating a complex licensure process; maintaining operations throughout the COVID-19 pandemic; and finally, planning for sustainability. In two years of operation, the mobile team cared for 297 unique patients during 1,286 total visits. More than one-third (36%) of patients received buprenorphine prescriptions. In contrast to BNHC's brick-and-mortar clinics, patients with OUD seen on the mobile unit were more representative of historically marginalized racial and ethnic groups, and people experiencing homelessness, evidencing improved, equitable addiction care access for these historically disadvantaged populations. Offering varied services on the mobile unit, such as wound care, syringe and safer smoking supplies, naloxone, and other basic medical care, was a key engagement strategy. This on-demand mobile model helped redress systemic disadvantages in access to addiction treatment and harm reduction services, reaching diverse individuals to offer lifesaving MOUD at a time of inequitable increases in overdose deaths.

Fat overload syndrome following intravenous lipid emulsion administration as antidote in suspected anesthetic intoxication: insights from a clinical and forensic case experience.

Abstract: Medication errors pose significant risks to patients' health, representing a relevant social and economic issue for the healthcare system. This study focuses on the life-threatening consequences of an overdose of intravenous lipid emulsion (ILE), used as an antidote for suspected bupivacaine intoxication in a young woman undergoing hip surgery. Shortly after administration of the local anesthetic, the woman experienced cardiac arrest and was admitted to the intensive care unit with severe respiratory failure, metabolic acidosis and deep coma. Despite medical intervention, her condition worsened, leading the medical team to administer ILE for suspected bupivacaine intoxication. The patient's condition did not improve and ultimately resulted in death. The autopsy highlighted a widespread presence of oily material in the vascular system, compatible with an overdose of ILE. At a checking, medical records reported a dose of ILE that was 4-fold higher than the recommended dose in this off-label indication. This case report highlights the important need for healthcare professionals to understand the risks of using ILE as an antidote. Adequate monitoring of these "sentinel events" and their critical evaluation can lead to the implementation of specific clinical risk management protocols to reduce the risk for the patient and contain healthcare costs.

Lomustine overdose in a patient with diffuse glioma: symptoms, management and outcome.

A male patient started PCV chemotherapy (a combination of procarbazine, lomustine and vincristine) for a recurrent oligodendroglioma grade 2. Unfortunately, our patient took an unintended overdose of lomustine during the first PCV course: instead of 160 mg absolute dose of lomustine on day 1 only, he consumed 160 mg absolute dose of lomustine for seven consecutive days to a total dose of 1120 mg. Pancytopenia became evident after 24 days, and several months of severe myelosuppression, infections, reduced general condition, and nutrition difficulties followed. Fortunately, our patient with time recovered his bone marrow function. However, the patient's quality of life was reduced for a long time and several lessons were learnt: oral and written information on chemotherapy is essential, but not always sufficient to ensure the correct dosing of patient-administered chemotherapy. Oral chemotherapeutics should be delivered as a single-dose supply or be administered by experienced health personnel.

Should high-dose N-acetylcysteine be given in cases of massive paracetamol overdoses: A narrative review.

N-acetylcysteine (NAC) is regarded as an effective treatment of paracetamol overdoses. However, in cases of "massive" paracetamol overdoses, recent studies indicate that patients may not be sufficiently treated with the standard dose of NAC (300 mg/kg over 20-21 h). The subject is further complicated because "massive overdoses" and "high-risk" are defined differently; some studies use the ingested amount (e.g., >40 g), and some studies use blood concentrations of paracetamol and transaminases. This narrative review investigates whether high-dose NAC significantly decreases the risk of hepatotoxicity in patients with massive paracetamol overdoses. Three observational studies were analysed; one study with 373 patients found no significant difference (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 0.49-3.29). One study with 79 patients found a significant difference (OR: 0.27, 95% CI: 0.08-0.94). The third study with 89 patients found a significant difference in hepatoxicity between the groups (p = 0.043). There are no solid evidence to support that treatment with high-dose NAC significantly reduces the rate of hepatotoxicity in patients presenting with massive paracetamol overdoses. Differences in inclusion criteria in the included studies make the studies incomparable. This paper shows that standardized inclusion is needed to determine whether a high-dose NAC regimen should be included in clinical practice.

Predictors of retention in heroin-assisted treatment in Denmark 2010-2018 - A record-linkage study.

INTRODUCTION: While randomized-controlled trials have shown that heroin-assisted treatment (HAT) is superior to methadone maintenance alone in treatment of refractory clients, little is known about client factors associated with retention in HAT in routine care. METHODS: This retrospective cohort study assessed predictors of retention in first treatment episode among a consecutive cohort of clients admitted to HAT in Denmark from 2010 to 2018, who could be matched to the Danish population register and for whom a Short Form Health Survey (SF-36) was available at admission (N = 432). The study derived predictors from client self-reports at intake and administrative data available in national registers. Cox proportional hazards regression modelled retention in treatment. RESULTS: The one-year retention rate was 69.63 % (95 % CI 65.06 %-73.74 %), and the median time in treatment was 2.45 years (95 % CI, 1.83-3.12). Bivariate analyses showed that retention was lower for clients who had recent cocaine or benzodiazepine use and among those who had experienced an overdose in the year prior to enrollment in HAT. Age below 40, recent illegal activity, poorer emotional wellbeing, previous residential treatment experience, and previous intensive outpatient treatment were also predictors of dropout from HAT. CONCLUSIONS: This observational study found that retention in HAT in routine care was similar to rates observed in randomized-controlled trials conducted in other countries. The results suggest that addressing polysubstance use as part of the HAT program may promote long-term retention, as may directing resources to certain subgroups identified at intake, including clients under 40 years and those who report recent criminal activity, emotional problems, or overdoses. The findings that previous residential treatment and intensive outpatient treatment were associated with dropout were unexpected.

Perspectives of key interest groups regarding supervised Consumption sites (SCS) and novel virtual harm reduction services / overdose response hotlines and applications: a qualitative Canadian study.

BACKGROUND: Supervised consumption sites (SCS) and overdose prevention sites (OPS) have been implemented across Canada to mitigate harms associated with illicit substance use. Despite their successes, they still contend with challenges that limit their accessibility and uptake. Overdose response hotlines and apps are novel virtual technologies reminiscent of informal "spotting" methods that may address some of the limitations. Here, we strove to qualitatively examine the factors that may encourage or deter utilization of these virtual services and SCS. METHODS: A total of 52 participants across Canada were recruited using convenience and snowball sampling methods. These included people with lived and living experience of substance use, family members of people with lived experience, healthcare providers, community harm reduction workers, and virtual harm reduction operators. Semi-structured telephone interviews were conducted and inductive thematic analysis was performed to identify the themes pertaining to SCS and virtual harm reduction. RESULTS: Participants viewed overdose response hotline and apps as an opportunity to consume substances without being hindered by logistical barriers (e.g., wait times), fear of law enforcement, invasion of privacy, and more. They also noted that these virtual services provided more flexibility for clients who opt for routes of consumption that are not supported by SCS, such as smoking. Overall, SCS was perceived to be better than virtual services at facilitating social connection, providing additional resources/referrals, as well as prompt response to overdose. CONCLUSION: In sum, participants viewed SCS and virtual services as filling different needs and gaps. This study adds to a growing body of literature which informs how virtual harm reduction services can serve as useful adjunct to more standard harm reduction methods.

Patterns of acetaminophen toxicity among patients with low-risk serum concentrations.

OBJECTIVE: In 2012, the Commission on Human Medicines mandated lowering the acetaminophen toxicity nomogram treatment threshold in the UK to 100 µg/ml at 4 h post-ingestion. The present study aim was to evaluate biochemical and liver toxicity patterns in patients who presented with acetaminophen overdose and had low serum acetaminophen concentrations (<150 µg/ml). METHODS: Patients admitted to the emergency department with a clear history of acute acetaminophen overdose with or without other medication or ethanol were consecutively enrolled into this retrospective cohort study. Patients with serum acetaminophen concentration >150 µg/ml or an unknown ingestion time were excluded. Data were extracted from electronic medical records and are presented as mean ± SD or median (interquartile range). RESULTS: A total of 103 patients were included (median age, 17 [4-21] years) and 80 (78%) were female. The median ingested acetaminophen dose was 5000 (2850-7650) mg. At baseline, the median serum acetaminophen concentration was 42 (4.5-64.8) µg/ml, and median alanine aminotransferase and aspartate aminotransferase levels were 22 (17-28) and 27 (16-45) IU/L, respectively. Twenty patients were treated with acetylcysteine, with none developing adverse reactions. No patient developed hepatotoxicity, including patients with initial multiple product ingestion or other risk factors. CONCLUSIONS: Patients presenting with an acute acetaminophen overdose with acetaminophen level <150 µg/ml, including patients with other risk factors, are at low risk of hepatotoxicity.

Assessment of high-dose acetylcysteine in acute high-risk paracetamol (acetaminophen) ingestion.

BACKGROUND: Prompt acetylcysteine treatment with standard doses (300 mg/kg over 21 h in divided doses) is almost universally effective in preventing hepatotoxicity after paracetamol (acetaminophen) overdose. However, hepatotoxicity is reported despite early treatment when paracetamol concentrations exceed 300 mg/L (1,985 µmol/L) at 4 h. Prior studies evaluating high-dose acetylcysteine to treat high-risk ingestions have shown mixed results. We compared outcomes in patients with high-risk ingestions receiving standard or high-dose acetylcysteine. METHODS: Records from a single poison center were reviewed from 1 January 2017 to 31 December 2022. We included cases of acute paracetamol ingestion treated with intravenous acetylcysteine with an initial paracetamol concentration above the "300 mg/L" (1,985 µmol/L) line on the Rumack-Matthew nomogram. We compared standard and high-dose acetylcysteine groups by odds ratios and multivariable logistic regression. We defined hepatotoxicity as aminotransferase activity >1,000 U/L. RESULTS: We included 190 cases. Fifty-six percent received standard-dose acetylcysteine while 44% received high-dose acetylcysteine. Treatment within 8 h yielded no difference in hepatotoxicity between groups (odds ratio 1.67, 95% CI 0.067-42.3). Among patients treated after 8 h, hepatoxicity was more common in the high-dose group (odds ratio 3.39, 95% CI 1.25-9.2) though odds of liver failure were similar (odds ratio 2.78, 95% CI 0.89-8.69). Eighty-eight percent of patients with hepatotoxicity had elevated aminotransferase activity at presentation. No patient died or received a liver transplant. DISCUSSION: Rates of hepatotoxicity were low in patients treated within 8 h regardless of acetylcysteine dose. Unexpectedly, high-dose acetylcysteine treatment was associated with an increased odds of hepatoxicity in those treated after 8 h, but most had abnormal aminotransferase activities at presentation and there was no difference in rates of liver failure. Limitations include the use of retrospective, voluntarily reported poison center data. CONCLUSIONS: Prompt treatment with acetylcysteine, regardless of dose, prevented hepatotoxicity in high-risk paracetamol ingestion.

Three consecutive cases of acute liver failure in young women due to acetaminophen overdose: insights into Japanese social issues and transplantation landscape.

Acetaminophen (APAP) is an over-the-counter (OTC) drug known worldwide for its safety and efficacy. However, in Japan, OTC drug overdose has become a prominent social problem in recent years due to stricter regulations for other drugs, especially among young people, and APAP is an increasing cause of acute liver injury due to overdose. This report describes three consecutive cases of acute liver failure in young women (22, 22 and 19 years old) due to APAP overdose in December 2023. Despite severe liver injury, indicated by high ALT levels and coagulopathy, these cases recovered without requiring liver transplantation. This report discusses three cases of acute liver failure in young Japanese women following APAP overdose, reflecting a national increase in such cases due to increased misuse of OTC drugs and societal factors. Key findings include the need for early treatment with N-acetylcysteine (NAC) and the importance of mental health assessment in the management of overdose patients. The cases underscore the need for prompt team-based care to prevent serious outcomes and highlight the complexity of liver transplantation decisions in Japan, highlighting the need for comprehensive strategies to address the escalating problem of APAP overdose.

Simultaneous multi-targeted forensic toxicological screening in biological matrices by MRM-IDA-EPI mode.

The toxicologist ascertains drug assumptions in case of paediatric intoxications and death for overdose. The analytical approach consists of initially screening and consequently confirming drug positivity. We developed a toxicological screening method and validated its use comparing the results with a LC-MS/MS analysis. The method identifies 751 drugs and metabolites (704 in positive and 47 in negative mode). Chromatographic separation was achieved eluting mobile phase A (10 mM ammonium formate) and B (0.05% formic acid in methanol) in gradient on Kinetex Phenyl-Hexyl (50 × 4.6 mm, 2.6 µm) with 0.7 mL/min flow rate for 11 min. Multiple Reaction Monitoring (MRM) was adopted as survey scan and, after an Information-Dependent Analysis (IDA) (threshold of 30,000 for positive and 1000 cps for negative mode), the Enhanced Product Ion (scan range: 50-700 amu) was triggered. The MS/MS spectrum generated was compared with one of the libraries for identification. Data processing was optimised through creation of rules. Sample preparation, mainly consisting of deproteinization and enzymatic hydrolysis, was set up for different matrices (blood, urine, vitreous humor, synovial fluid, cadaveric tissues and larvae). Cut-off for most analytes resulted in the lowest concentration tested. When the results from the screening and LC-MS/MS analysis were compared, an optimal percentage of agreement (100%) was assessed for all matrices. Method applicability was evaluated on real paediatric intoxications and forensic cases. In conclusion, we proposed a multi-targeted, fast, sensitive and specific MRM-IDA-EPI screening having an extensive use in different toxicological fields.

"Coke in the Dope": The Underrecognized Complications of a Cocaine-Adulterated Fentanyl Supply.

ABSTRACT: The opioid crisis, particularly the "fourth wave" involving fentanyl and stimulants, has been responsible for an alarming increase in overdose deaths in the United States. Although fentanyl contamination in cocaine has gained significant attention, the converse-cocaine-adulterated fentanyl-has been largely overlooked despite its health implications. The rise in concurrent cocaine and fentanyl overdose deaths could be attributed to various factors, from intentional polysubstance use to unintentional adulterations. Cocaine-related health issues may amplify the problem. Four potential pathways for the increased risk of overdose with cocaine-adulterated opioids include enhanced drug reinforcement, potential overdose risk with switching drug samples, altered metabolism of medications used for opioid use disorder, and increased myocardial demand juxtaposed with opioid-induced respiratory depression. With these risks, the importance of drug testing becomes paramount in the unregulated drug market. As polysubstance use overdoses surge, there is an urgent need to understand how drug supplies are changing in order to effectively identify appropriate harm reduction strategies. Specifically, further research is needed evaluating complications of low-level cocaine exposure with chronic/persistent opioid use. The hazards associated with cocaine-adulterated fentanyl emphasize the significance of understanding not only fentanyl's presence in cocaine but also cocaine's role in the fentanyl supply.

"Fighting demons": Stigma and shifting norms in explicit mention of overdose in obituaries, 2010-2019.

Obituaries are often the only published record of an individual's life and elicit community reactions, including stigmatization. Because obituaries are typically written by the bereaved, their content reflects the writer's perceptions of mores governing the social context of the next-of-kin and decedent. When a cause of death is stigmatized, it can influence the way the bereaved write the obituary. However, what constitutes a stigmatized cause of death may change as larger societal discourses of morality shift and conditions or events become framed differently. Using a sample of obituaries (N = 210) from obituary aggregator Legacy.com of "off-time," or premature, deaths in West Virginia from 2010, 2015, 2017, and 2019, this article explores whether the presentation of overdose deaths in obituaries changes alongside the shift in the public framing of the opioid crisis as medical rather than criminal. I find obituaries including terms associated with drug use and overdose become both more common and explicit over the course of the study period. This suggests that the shift in public framing of the opioid crisis from criminalization to medicalization corresponds with a decrease in drug stigmatization in obituaries. Obituary analysis can be a useful means of exploring the stigmatization of other controversial causes of death, such as suicide, cirrhosis, and lung cancer.

Evaluating the Risk Index for Serious Prescription Opioid-Induced Respiratory Depression or Overdose in Patients with Cancer.

The Commercially Insured health Plan Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (CIP-RIOSORD) is an evidence-based tool to determine serious opioid-induced respiratory depression (OIRD) or overdose risk. The CIP-RIOSORD total score determines a risk class and estimates the probability for an OIRD event within the next 6 months. We performed a single-center, retrospective analysis to determine CIP-RIOSORD baseline scores and the most common predictive factors in patients with cancer. Patients (n = 160) were split into new consultations (n = 83, Group 1) versus the first documented follow-up consultation (n = 77, Group 2). Most patients were Caucasian women with metastatic gastrointestinal cancer. CIP-RIOSORD scores for Group 1 patients were 14.8 ± 15.2 (mean ± SD, risk class 4). Group 2 patients had higher CIP-RIOSORD scores (16.6 ± 14.9, risk class 4). For Group 1, the most common CIP-RIOSORD predictive factors were use of a long-acting opioid formulation (n = 24, 29%) and daily oral morphine equivalent (OME) ≥100 (n = 20, 24%); for Group 2, predictive factors were use of an antidepressant (n = 34, 44%) and a long-acting opioid formulation (n = 27, 35%). Based on the CIP-RIOSORD, there is a 15% probability of experiencing a serious OIRD event or overdose within the next 6 months.

The Insidious Enemy of the Liver: The Situation in Childhood Acetaminophen Poisoning and Early N-AC Treatment.

METHODS: This study was designed as a cross-sectional, observational, retrospective study. The variables of the study were paracetamol overdose, demographic information, poisoning mechanisms, clinical, laboratory findings, and clinical progression of the cases. The cases compared in whom treatment was initiated within the first 8 hours after poisoning and those in whom it was not. χ 2 , t test, and logistic regression analyses were conducted at appropriate facilities. RESULTS: Three hundred forty-eight cases were included in the study. N-AC treatment was initiated within the first 8 hours after poisoning in 322 cases (92.5%), and 26 cases received N-AC treatment after 8 hours after poisoning. Liver toxicity developed in 6 cases (1.7%), and indications for liver transplantation were met in 36 cases (10.3%). Among the 26 cases for which treatment was not initiated within the first 8 hours, 18 cases (69.2%) had indications for liver transplantation ( P < 0.01). It was found that N-AC within the first 8 hours reduced the risk by 43 times ( P = 0.02) and being older than 6 years, being admitted to the intensive care unit, and having alanine aminotransferase values above 1000 U/L increased the risk significantly ( P = 0.009, P = 0.005, P < 0.001). When a receiver operating characteristic curve was plotted for the 4th-hour blood acetaminophen level to predict liver transplantation, a value of 684.5 µg/mL emerged with 89% sensitivity and 93% specificity (area under the curve, 0.951). CONCLUSIONS: As a result, this study demonstrates the protective effect of early-initiated N-AC therapy on liver toxicity in pediatric acetaminophen poisoning cases. It also highlights a significant impact of gastrointestinal decontamination methods.

Accidental calcium, magnesium, potassium and sodium oxybates (Xywave) overdose: mistiming of a single night's narcolepsy medication leading to respiratory failure requiring mechanical ventilation.

While typically thought of as an illicit substance, oxybate salts or gamma-hydroxybutyrate (GHB) has more recently been prescribed to treat narcolepsy by enhancing night-time sleep resulting in decreased daytime drowsiness. This case involves a college-aged female with prescribed GHB for narcolepsy who took her second nightly dose too early. This resulted in mental depression, respiratory failure, intubation and mechanical ventilation. The patient was successfully extubated in the intensive care unit several hours later with no residual morbidity. We were unable to identify any prior reports of mixed-salt oxybate toxicity following mistimed drug administration. This case should serve as a warning to emergency physicians to be on the lookout for GHB as part of the differential diagnosis for patients with narcolepsy presenting with altered mental status. It should also serve as a warning to patients and prescribers that this medication can have outcomes that require immediate medical intervention.

Case Series: Hepatic and Splenic Titanium Dioxide Deposition in Association With Intravenous Drug Use.

ABSTRACT: Titanium dioxide is a versatile compound that is found in a variety of consumer products, medical hardware, and pharmaceuticals. Although oral and topical ingestion of this compound is common, intravenous introduction is much less common. We present three cases where significant titanium dioxide deposits were identified in liver and splenic tissue of three decedents, all of whom died of illicit drug overdose in the same geographic area and had fentanyl and its metabolites in blood on postmortem toxicologic testing. At autopsy, liver sections had a granular texture with fine white stippling grossly, and histologic examination of hepatic and splenic tissues showed scattered patches of black granular material with pink birefringence. Energy-dispersive x-ray spectroscopy performed on these tissues revealed the presences of clusters of titanium dioxide. Immunohistochemical staining of both the liver and spleen with CD68 confirmed the titanium dioxide clusters were within macrophages. Intravenous titanium dioxide nanoparticle elimination studies in rats suggest a time sensitive period for this elimination, with a transient period of pigment deposition between 1-58 days following injection. If a time-dependent link between titanium dioxide pigment deposition within tissues and intravenous drug use can be shown, this could be a valuable tool for Pathologists.