Endoscopic removal of a gastric pharmacobezoar induced by clomipramine, lorazepam, and domperidone overdose: a case report.

INTRODUCTION: Gastric pharmacobezoars are a rare entity that can induce mechanical gastric outlet obstructions and sometimes prolong toxic pharmacological effects. Certain medications, such as sustained-release forms, contain cellulose derivatives that may contribute to the adhesion between pills and lead to the creation of an aggregate resulting in a pharmacobezoar. Case reports are rare, and official guidelines are needed to help medical teams choose proper treatment options. CASE PRESENTATION: Our patient was a 40-year-old Caucasian woman with borderline personality disorder and active suicidal thoughts who was found unconscious after a massive drug consumption of slow-release clomipramine, lorazepam, and domperidone. On her arrival in the emergency room, endotracheal intubation was preformed to protect her airway, and a chest x-ray revealed multiple coffee grain-sized opaque masses in the stomach. She was treated with activated charcoal followed by two endoscopic gastric decontaminations 12 h apart in order to extract a massive gastric pharmacobezoar by manual removal of the tablets. CONCLUSION: This case demonstrates that in the case of a massive drug consumption, a pharmacobezoar should be suspected, particularly when cellulose-coated pills are ingested. Severe poisoning due to delayed drug release from the gastric aggregate is a potential complication. Detection by x-ray is crucial, and treatment is centered on removal of the aggregate. The technique of decontamination varies among experts, and no formal recommendations exist to date. It seems reasonable that endoscopic evaluation should be performed in order to determine the appropriate technique of decontamination. Care should be patient-oriented and take into account the clinical presentation and any organ failure, and it should not be determined solely by the suspected medication ingested. Thus, serum levels are not sufficient to guide management of tricyclic antidepressant intoxication.

Opioid tolerance and clinically recognized opioid poisoning among patients prescribed extended-release long-acting opioids.

BACKGROUND: In recognition of potential for increased overdose risk, drug labels for extended-release and long-acting (ER/LA) opioids emphasize the need for established opioid tolerance prior to initiating high dosages. OBJECTIVES: Describe the proportion of patients with opioid tolerance prior to initiation of 90 morphine milligram equivalents (MME) ER/LA opioids and examine subsequent risk of opioid poisoning. METHODS: We used Truven Health Analytics' MarketScan Databases (2006-2015) to identify patients initiating ER/LA opioids ≥90 MME. We examined prescription histories and describe the proportion of initiators with opioid tolerance (defined as ≥7 days of 60 MME in the prior 14 days). We adjusted for age, sex, year of initiation, and baseline comorbidities using inverse probability of treatment weighted Cox proportional hazards models. We estimated adjusted hazard ratios and 95% confidence intervals for the effect of opioid tolerance on the risk of clinically recognized opioid poisoning (based on diagnosis codes) in specific periods (0-7, 8-30, 31-90, and 91-365 days) following initiation. RESULTS: Among 372 038 initiators, 38% did not meet opioid tolerance criteria. The proportion of nontolerant initiators was highest among those initiating methadone (44%) and fentanyl (42%). Nontolerant patients were 37% more likely to be diagnosed with opioid poisoning (adjusted hazard ratios = 1.37 [1.07, 1.76]) in the week following ER/LA initiation. CONCLUSIONS: Over one-third of patients initiating ≥90 MME ER/LA opioids did not have evidence of opioid tolerance. The 7 days following high dose ER/LA initiation may represent a high-risk period for clinically diagnosed opioid poisoning in patients who do not have prior opioid tolerance.

Comparative out-of-hospital mortality of long-acting opioids prescribed for non-cancer pain: A retrospective cohort study.

PURPOSE: Despite significant growth of opioid prescriptions, only limited data are available regarding the comparative safety of long-acting opioids for chronic non-cancer pain. Recent data suggest that transdermal fentanyl and oxycodone CR may have greater toxicity than morphine SR in patients with non-cancer pain. Thus, we compared the risk of out-of-hospital deaths in patients with non-cancer pain filling prescriptions for transdermal fentanyl or oxycodone CR with that for morphine SR. METHODS: We conducted a retrospective cohort study in 50 658 patients enrolled in Tennessee Medicaid who filled prescriptions for transdermal fentanyl (n = 8717), oxycodone CR (n = 14 118), or morphine SR (n = 27 823) between 1999 and 2011. We excluded individuals with cancer or other life-threatening diagnoses and used propensity scores to adjust for multiple potential confounders. The primary outcome was out-of-hospital mortality. RESULTS: During 44 385 person-years of follow-up, 689 patients died. The out-of-hospital mortality rate among all study subjects was 155/10 000 patient-years. Contrary to earlier data suggesting greater risk, mortality was not significantly different in patients filling prescriptions for transdermal fentanyl compared with morphine SR (adjusted HR = 0.96, 95% C.I.: 0.77-1.21); moreover, patients filling prescriptions for oxycodone CR had lower mortality risk compared with those filling prescriptions for morphine SR (adjusted HR = 0.79, 95% C.I. 0.66-0.95). CONCLUSION: In the study population, long-acting opioids for non-cancer pain were associated with high out-of-hospital mortality rates. We found comparable out-of-hospital mortality risks associated with transdermal fentanyl and morphine SR. The risk of out-of-hospital death for oxycodone CR was lower than that for morphine SR.

Modified release paracetamol overdose: a prospective observational study (ATOM-3).

BACKGROUND: Modified-release (MR) paracetamol is available in many countries as 665 mg tablets of which 69% is MR and 31% is immediate release. There are concerns that MR paracetamol overdose has higher rates of liver injury despite standard treatment algorithms. The objective of this study was to describe the clinical characteristics and outcomes of acute MR paracetamol overdose. METHODS: Prospective observational study, recruiting patients from January 2013 to June 2017, from five clinical toxicology units and calls to two Poisons Information Centres in Australia. Included were patients >14 years who ingested ≥10 g or 200 mg/kg (whichever is less) of MR paracetamol. Data collected included demographics, ingestion history, pathology results, treatments, and outcomes including hepatotoxicity (ALT >1000 U/L). RESULTS: In total, 116 patients were recruited, 85(73%) were female. The median dose ingested was 32 g (IQR: 20-49 g) and median time to presentation was 3 h (IQR: 2-9 h). 78(67%) had an initial paracetamol concentration above the nomogram line (150 mg/L at 4 h). A further 12(10%) crossed the nomogram after repeat paracetamol measurements, of which five crossed after two non-toxic levels 4 h apart. Six had a double paracetamol peak, in three occurring >24 h post-ingestion. 113(97%) received acetylcysteine of which 67 received prolonged treatment beyond the standard 21 h. This was because of an elevated paracetamol concentration at the completion of acetylcysteine in 39 (median paracetamol concentration 25 mg/L, IQR: 16-62 mg/L). 21 (18%) developed hepatotoxicity, including six treated within 8 h of ingestion. Activated charcoal and double doses of acetylcysteine did not significantly decrease the risk of hepatotoxicity. CONCLUSIONS: Drug regulatory authorities are considering restrictions on MR paracetamol preparations. Following an acute MR paracetamol overdose, this study found that many patients had a persistently elevated paracetamol concentrations, many required prolonged treatment and some developed liver injury despite early acetylcysteine treatment. Furthermore, activated charcoal and increased acetylcysteine did not appear to significantly alter the risk of liver injury. Hence, research into better treatment strategies is required. TRIAL REGISTRATION: Australian Toxicology Monitoring (ATOM) Study - Australian Paracetamol Project: ACTRN12612001240831 (ANZCTR) Date of registration: 23/11/2012.

Deliberate self-poisoning with long-acting anticoagulant rodenticides.

Long-acting anticoagulant rodenticides, also called superwarfarins, are known for their greater potency, longer half-life and delayed onset of symptoms. Cases of superwarfarin poisoning can pose a diagnostic and clinical challenge due to a wide array of presentations and prolonged severe coagulopathy requiring months of high-dose oral vitamin K therapy. The most common presentation of long-acting anticoagulant rodenticide poisoning is mucocutaneous bleeding, with other common presentations including haematuria, gingival bleeding, epistaxis and gastrointestinal bleeding. We discuss a case of deliberate self-poisoning with long-acting anticoagulant rodenticides presenting with haematuria and coagulation values above measurable limits. This case is important as it required immediate and maintenance therapy in order to prevent profound bleeding, as well as the evaluation of the patient's psychosocial factors to ensure medical compliance and to prevent refractory complications or repeated self-harm.

Gastric pharmacobezoars in quetiapine extended-release overdose: a case series.

OBJECTIVE: Although extended-release (XR) formulations are recognized to bear some risk of pharmacobezoar formation in overdose, there are no previously documented reports of this phenomenon with quetiapine. We describe nine cases of pharmacobezoar formation in acute quetiapine XR overdose. METHODS: Observational case series of all patients who underwent gastroscopy after quetiapine XR overdose, which were reported by physicians to the Swiss Toxicological Information Centre between January 2010 and December 2012, with detailed analysis of cases with documented pharmacobezoar. RESULTS: Gastric pharmacobezoars were detected in 9 out of 19 gastroscopic evaluations performed during the study period. All these patients ingested a large dose of quetiapine XR (10-61 tablets; 6-24.4 g quetiapine). All patients but one also coingested at least one other substance, and in three cases another XR drug formulation. Gastroscopic pharmacobezoar removal was achieved without complications in all patients, but was difficult due to the particular "gelatinous-sticky-pasty" consistency of the concretion. The subsequent clinical course was favorable. CONCLUSIONS: The possibility of pharmacobezoar formation following a large quetiapine XR overdose should be considered, as this may influence acute patient management. Complete endoscopic pharmacobezoar removal may be a promising approach in selected cases, but further studies are needed to define its role.

Double peak and prolonged absorption after large acetaminophen extended release and diphenhydramine ingestion.

Acetaminophen and acetaminophen combination products are the most frequent medications involved in intentional and unintentional poisonings. The 2008 National Poison Data System compiled by the American Association of Poison Control Centers documented 98,578 acetaminophen-related poisonings, which includes 91 fatalities. Very few case reports of ingestions of acetaminophen extended release with anticholinergics are reported in the literature.

Whole fentanyl patch ingestion: a multi-center case series.

BACKGROUND: Fentanyl is a potent synthetic opioid with large abuse potential. A common preparation of fentanyl is a sustained-release transdermal patch. To our knowledge, there are only two published case reports of whole patch ingestion. A case series of 76 patients with a history of whole patch ingestion is reported. STUDY OBJECTIVES: To characterize whole fentanyl patch ingestion to develop a clinical guideline for management. METHODS: This was a retrospective review of all patients who ingested intact fentanyl patches as reported to three regional poison information centers (RPIC) from 2000 to 2008. The three RPIC medical record databases were queried for all exposures with a substance code matching the Micromedex® (Thomson Reuters, New York, NY) fentanyl product codes. Collected data included: age, gender, reason for the exposure, number of patches ingested, dose (µg/h), symptoms, symptom onset and duration, treatment hospital flow (level of care), and outcome. RESULTS: A total of 76 patients met the inclusion criteria. Two patients had both time of onset and symptom duration documented. In both patients, the signs and symptoms developed within 2 h of the exposure, and the patients were asymptomatic at 6½ and 9 h, respectively. Fifty-eight (78.3%) patients were admitted. Of those patients who were admitted, 56 (96.5%) were admitted to a critical care unit. Fourteen patients required intubation, and naloxone infusions were documented in eight cases. CONCLUSION: Ingestion of whole fentanyl patches may lead to prolonged and significant toxicity based on these poison center data.

Decontamination and enhanced elimination in sustained-release potassium chloride poisoning.

Potassium chloride poisoning can be potentially life-threatening, particularly in massive ingestions of sustained-release preparations. Profound hyperkalaemia, developing over several hours, can lead to cardiac arrhythmias and death. This case series reports three episodes of sustained-release potassium chloride poisoning in two individuals requiring whole bowel irrigation or haemodialysis. The first two episodes, in the same patient, illustrate the contrast between the successful use of decontamination versus the need for haemodialysis. The second case, in a child, illustrates the need for tertiary level paediatric expertise in managing this type of poisoning. Whole bowel irrigation with polyethylene glycol is a resource-intensive procedure most beneficial when large numbers of radio-opaque tablets are seen in the stomach. In cases where most of the tablet matter has already been absorbed, extracorporeal methods of rapidly reducing the total body burden of potassium, such as haemodialysis, might be life-saving.

Paliperidone overdose with delayed onset of toxicity.

Paliperidone, or 9-hydroxy risperidone, is the newest atypical antipsychotic agent to be approved for use by the Food and Drug Administration. Despite being the primary active metabolite of risperidone, paliperidone differs in several ways from risperidone. The most notable difference is that paliperidone is formulated as an extended-release product. We present a case of a 14-year-old, 59-kg girl with a history of psychosis and major depressive disorder who developed toxicity after an ingestion of 180 mg (3.1 mg/kg) of paliperidone. This case is not only one of the first cases of paliperidone overdose described in the literature but also is unique in that it describes delayed onset of toxicity, as well as extended duration of symptoms.

Niacin toxicity resulting from urine drug test evasion.

BACKGROUND: Niacin, a well-established agent for treating dyslipidemia, has been promoted on the Internet as a method for passing urine drug screening, although there are no data to support its use for this purpose. In a handful of cases, this practice has resulted in serious niacin toxicity. OBJECTIVES: The aim of this article is to describe a unique clinical presentation of niacin toxicity. CASE REPORT: A 23-year-old previously healthy man presented to an Emergency Department with altered mental status, fever, acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia, and coagulopathy. It was revealed that he had taken approximately 22.5 g of sustained-release niacin over the preceding 48 h in an attempt to pass a pre-employment urine drug screen. After a complicated hospital course that included mechanical ventilation for respiratory failure and hemodialysis for acute renal failure, the patient made a full recovery and was discharged 10 days after his initial presentation. CONCLUSION: After a massive niacin overdose, the young man in this case presented with a complex clinical picture that mimicked concurrent thrombotic thrombocytopenic purpura and disseminated intravascular coagulation. Although this patient was fortunate to make a full recovery, the case highlights the potential for multi-system toxicity with niacin overdose, and the potential for harm posed by medical misinformation on the Internet.

Bupropion toxicokinetic: a case report.

CONTEXT: The toxicokinetics of sustained-release bupropion are not well described. CASE: A 23-year-old Caucasian male took an overdose of 5,700 mg of sustained release bupropion with no co-ingestant. Venous serum samples were assayed for bupropion concentrations over the next 5 days. The peak concentration was 1.114 mg/L. The observed T(max) was found to be 8.25 h, the calculated alpha half-life 10.9 h (+/-SE of 4.47%), and the calculated beta half-life 19.8 h (+/-SE 12.62%). The alpha half-life and T(max) differ significantly from those seen in therapeutic doses. DISCUSSION: Bezoar formation may underlie these differences. Interventions which reduce the absorption of sustained release bupropion may be effective in overdose.

A case of suicide attempt with long-acting methylphenidate (Concerta).

The prescribed use of methylphenidate in the treatment of attention deficit hyperactivity disorder (ADHD) is widespread. The intranasal and parenteral abuse of methylphenidate (Ritalin) among teenagers is becoming increasingly more common, and deaths have been reported. Newer medical treatment options of long-acting stimulants offer effective treatment with a lower risk of abuse potential. We describe a case of a 17-year-old girl who had attempted suicide by ingesting 270 mg of Concerta. During the third years of treatment with Concerta, parents of patient reported that the patient had a depressive mood in the last week, and had attempted suicide with five tablets of Concerta 54 mg. She was sent to a local hospital with a diagnosis of long-acting methylphenidate overdose. All of vital and laboratory findings were normal except heart rate, which was 132 beats/min. Since more than 3 h have elapsed after the time of ingestion, activated charcoal administration was not carried out at the hospital. She was only observed for 12 h at the emergency department and later discharged from the hospital. While long-acting stimulants offer lower risk of abuse, their greater availability increases the likelihood of ingestion of this nature. Education of clinicians and families to be aware of this risk should reduce the frequency of this complication of treatment.

Case report: intoxication with high dose of long-acting methylphenidate (Concerta(®)) in a suicidal 14-year-old girl.

A 14-year-old girl with suicidal ideation was presented to the paediatric hospital about 2 h after ingestion of 21 long-acting methylphenidate (MPH) 54-mg tablets (1,134 mg Concerta(®)). At admission signs of sympathomimetic syndrome were observed like agitation, visual hallucinations, slight hypertension, and sinus tachycardia. Treatment included prevention of absorption (30 g activated charcoal orally) and careful observation related to the overstimulation of the sympathic system. Despite the intake of charcoal, the serum concentrations of MPH were 107 and 93 ng/ml 2.5 and 22 h after ingestion of MPH tablets. No support of vital functions was necessary. The girl made a full recovery and was discharged after 3 days of care at the paediatric clinic and referred to the child and adolescent psychiatric department. Exposure to a huge overdose of long-acting MPH exhibited acute sympathomimetic toxicity but no life-threatening symptoms in this patient. Thus this case report suggests that patients intoxicated with high dose long-acting MPH formulations can recover without sequelae when managed properly.

Surprisingly delayed escalation of severe verapamil poisoning.

We present a case report of intoxication by a potentially lethal dose of sustained-release verapamil with delayed escalation of complications. The patient was hospitalized 1.5 h after an attempted suicide with a very high dose of verapamil sustained-release (7.2 g). On admission the plasma concentrations were extremely high (3600 ng/l). Heart rate and blood pressure declined slowly with a surprising sudden escalation on the third day coupled with hemodynamic collapse and loss of consciousness. Complete recovery was achieved in spite of 2 h of extreme hypotension. We outline the clinical course, a need for massive bowel irrigation in case of sustained-release medication, the timing of a temporary pacing and the effect of centralization of circulation even on invasively measured blood pressure.