Sublingual administration of atropine eye drops for treating organophosphorus poisoning.

An 89-year-old patient with fenitrothion toxicity received sublingual atropine eye drops, reducing the intravenous atropine requirement. This alternative method enabled rapid rehabilitation, and he walked unaided, leading to discharge.

Guanfacine poisoning resulting in transient ST-segment elevation: a case report.

BACKGROUND: Guanfacine is an alpha-2 adrenergic agonist that decreases norepinephrine release and sympathetic outflow. With the increased use of guanfacine for attention-deficit hyperactivity disorder (ADHD), reports of guanfacine poisoning have also risen. CASE PRESENTATION: A 15-year-old male (height: 170 cm, weight: 48 kg), who was taking 2 mg/day of guanfacine for ADHD, was brought to our emergency department after ingesting 40 tablets of guanfacine due to poor exam results. He presented with impaired consciousness and sinus bradycardia on an electrocardiogram (ECG), leading to diagnosis of guanfacine poisoning. Gastric lavage (5 L) was performed, and activated charcoal was administered. Although his consciousness gradually recovered, he developed ST-segment elevation on the ECG. Despite the absence of chest pain and elevated myocardial enzymes, coronary artery stenosis was not observed on coronary artery computed tomography. As his blood guanfacine level decreased, his ECG returned to normal. CONCLUSIONS: This case highlights the need for careful monitoring of guanfacine poisoning patients due to the potential for various cardiovascular events.

The efficacy of intermittent hemodialysis in severe bromovalerylurea poisoning.

Bromvalerylurea (BVU) is a sedative-hypnotic drug with a high risk of acute poisoning. In the present case, hemodialysis (HD) was introduced in a patient with severe BVU poisoning who later demonstrated respiratory arrest, and then HD clearances (CLHD) were assessed in detail. A 20-year-old female was transported to the emergency department by ambulance, an estimated two to four hours after orally ingesting 144 tablets of Utto® (12,000 mg BVU) in a suicide attempt. The patient was comatose on arrival. After intratracheal intubation, 50 g of activated charcoal was administered through nasogastric tube. She was then transferred to the intensive care unit. Ten hours after arrival at the hospital, her light reflex, contralateral light reflex, corneal reflex, and spontaneous respiration disappeared, resulting in an introduction of HD 16 h after arrival. Eighteen hours after arrival, her light reflex, contralateral light reflex, and corneal reflexes had recovered. Twenty-one hours after arrival, her consciousness level improved and the patient was weaned from HD. During HD treatment, blood samples were collected pre-HD and post-HD every hour. Serum BVU concentrations were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The median CLHD was 133.61 mL/min, and the systemic clearance (CLSYS) was 117.77 mL/min. Higher CLHD of BVUs over CLSYS suggests that HD may play an important role in the treatment of severe BVU poisoning.

Severe aconite poisoning successfully treated with veno-arterial extracorporeal membrane oxygenation: A case report.

BACKGROUND: Most species of aconite contain highly toxic aconitines, the oral ingestion of which can be fatal, primarily because they cause ventricular arrhythmias. We describe a case of severe aconite poisoning that was successfully treated through veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and in which detailed toxicological analyses of the aconite roots and biological samples were performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). CASE SUMMARY: A 23-year-old male presented to the emergency room with circulatory collapse and ventricular arrhythmia after ingesting approximately half of a root labeled, "Aconitum japonicum Thunb". Two hours after arrival, VA-ECMO was initiated as circulatory collapse became refractory to antiarrhythmics and vasopressors. Nine hours after arrival, an electrocardiogram revealed a return to sinus rhythm. The patient was weaned off VA-ECMO and the ventilator on hospital days 3 and 5, respectively. On hospital day 15, he was transferred to a psychiatric hospital. The other half of the root and his biological samples were toxicologically analyzed using LC-MS/MS, revealing 244.3 mg/kg of aconitine and 24.7 mg/kg of mesaconitine in the root. Serum on admission contained 1.50 ng/mL of aconitine. Beyond hospital day 2, neither were detected. Urine on admission showed 149.09 ng/mL of aconitine and 3.59 ng/mL of mesaconitine, but these rapidly decreased after hospital day 3. CONCLUSION: The key to saving the life of a patient with severe aconite poisoning is to introduce VA-ECMO as soon as possible.

Unveiling the Rare Presentation of Acetylsalicylate Overdose: Grand Round.

BACKGROUND: This case report highlights a rare occurrence of aspirin overdose presenting only as severe coagulopathy. CASE PRESENTATION: An 85-year-old woman was admitted to the hospital with multiple lumbar vertebral compression fractures causing severe back pain. The patient had self-medicated with excessive consumption of Bufferin A containing 330 mg of aspirin. On arrival, she showed no typical symptoms of salicylate toxicity, such as nausea, vomiting, hyperventilation, tinnitus, or hearing loss. However, blood work revealed a significant decrease in vitamin K-dependent coagulation factors leading to coagulopathy. The administration of 20-mg menatetrenone (vitamin K) resulted in rapid improvement in coagulation abnormalities. The patient's blood salicylate level was later determined to be 42.7 mg/dL. DISCUSSION: Acute salicylate poisoning is known to cause coagulopathy because of the inhibition of vitamin K-dependent coagulation factors. However, this case is unique because it demonstrates coagulopathy as the sole manifestation of aspirin toxicity without any other symptoms. CONCLUSIONS: This case highlights the importance of considering the possibility of aspirin toxicity in patients with coagulopathy, especially those who are regularly consuming aspirin.

Fatal poisoning due to ingestion of boiled oleander leaf extract.

Nerium oleander is an ornamental evergreen shrub belonging to the family Apocynaceae. The Apocynaceae family includes the attractive evergreen shrub known as oleander. The cardiotoxic glycoside, oleandrin, is present in all portions of the common oleander plant. Oleander consumption can result in deadly situations accidentally or as a suicide attempt. After consuming kettle-boiled oleander leaf extract as part of a suicide attempt, an 80-year-old man was discovered comatose in his home and taken to our emergency room. The patient's heart rate was 30 beats per minute, and he had hypotension. Arterial blood gas analysis revealed remarkable metabolic acidosis and hyperkalemia (K: 7.7 mEq/L). An electrocardiogram showed a wide QRS wave, similar to a sine curve. The patient collapsed following cardiac arrest soon after hospital arrival. Veno-arterial extracorporeal membrane oxygenation was initiated; however, the patient eventually died. The serum level of oleandrin at hospital arrival, subsequently measured by LC-MS/MS, was found to be 33.4 ng/mL, far above the levels reported in previous fatal cases.

Severe caffeine poisoning treated with intermittent hemodialysis under circulatory support.

Caffeine poisoning can cause fatal ventricular arrhythmias. In this report, we describe a case of severe caffeine poisoning with extraordinarily high blood caffeine levels. Despite developing refractory ventricular fibrillation, the patient was successfully treated with intermittent hemodialysis (IHD) under circulatory support by venoarterial extracorporeal membrane oxygenation (VA-ECMO). A 22-year-old male was transported to our hospital approximately 2.5 h after ingesting 200 highly caffeinated tablets (200 mg/tablet) (40 g caffeine total) in a suicide attempt. On arrival, the patient vomited frequently with a Glasgow Coma Scale score E3V2M5, heart rate 185 beats/min, and a blood pressure of 97/62 mmHg. Shortly after arrival, the patient developed ventricular fibrillation which was refractory either to three electrical defibrillations or antiarrhythmic drugs, resulting in endotracheal intubation for mechanical ventilation and VA-ECMO. Starting from 2 h after arrival, intermittent hemodialysis (IHD) was performed for 11 h, which markedly improved clinical symptoms and circulatory parameters. Serum caffeine level was 454.9 mg/dL upon arrival at the hospital, but it decreased to 55.5 mg/dL by the end of IHD treatment. Renal replacement therapy (RRT) including intermittent hemodiafiltration, continuous hemodiafiltration, and IHD was continued because of rhabdomyolysis with myoglobinuria and secondary caused acute kidney injury. The patient was weaned off VA-ECMO on hospital day 7, extubated on hospital day 18, weaned from RRT on hospital day 46, and was transferred to another hospital for physical rehabilitation on hospital day 113. IHD under circulatory support by VA-ECMO should be considered in severe caffeine poisoning causing potentially fatal arrhythmias.

Poisoning by abnormally high blood phenobarbital concentration treated with extracorporeal therapy.

Phenobarbital poisoning, which may cause circulatory collapse as well as respiratory arrest in severe cases, has one of the highest mortality rates among acute drug poisonings. A 58-year-old man arrived at the emergency room in a deep coma (Glasgow Coma Scale E1V1M1) after taking an unknown dose of phenobarbital which had been prescribed for his cat's seizures. Venous blood gas analysis revealed hypercapnia (PvCO2: 113.0 mmHg) and a blood phenobarbital concentration of 197.3 µg/mL. Shortly after his arrival, respiratory arrest and circulatory collapse occurred. Mechanical ventilation after intubation, intravenous noradrenaline infusion, and multiple-dose activated charcoal through a nasogastric tube was started. Six hours after arrival, blood phenobarbital concentration was abnormally elevated to 356.8 µg/mL with circulatory collapse requiring an increased dose of intravenous noradrenaline infusion (up to 0.13 µg/kg/min). Continuous renal replacement therapy including high flow continuous hemodialysis was performed until hospital day 5, during which blood phenobarbital concentration decreased to 96.2 µg/mL on hospital day 4, resulting in a sufficient resumption of spontaneous breathing and full improvement of circulatory collapse. A search of the literature revealed that the peak phenobarbital concentration in the present case exceeded those of fatal cases, as well as those of survivors of acute phenobarbital poisoning. However, the patient was successfully treated with continuous renal replacement therapy. Among modalities of extracorporeal treatment, continuous renal replacement therapy could be considered if a patient's circulation is unstable.

Detection of major psychoactive compounds (safrole, myristicin, and elemicin) of nutmeg in human serum via GC-MS/MS using MonoSpin® extraction: Application in a nutmeg poisoning case.

Nutmeg is an inexpensive, readily available spice used in a variety of recipes. However, the use of nutmeg powder as a recreational drug for its hallucinogenic effects is resulting in an increase in overdose rates. We encountered a male patient being hospitalized after ingesting 75 g of commercially available nutmeg powder with the intent of committing suicide. There are no available reports documenting the toxic or comatose-fatal blood concentrations or time-course of drug action in cases of nutmeg poisoning. Therefore, to improve patient management, we endeavored to determine the blood serum levels and time-course of the major psychoactive compounds (safrole, myristicin, and elemicin) present in nutmeg. We designed a simple and reliable method using the MonoSpin® extraction kit and gas chromatography-tandem mass spectrometry to detect the presence of these psychoactive compounds in human serum. The method had detection and quantitation limits of 0.14-0.16 and 0.5 ng/mL (lowest calibration points), respectively. The calibration curves displayed excellent linearity (0.996-0.997) for all three compounds at 0.5-300 ng/mL blood concentrations. The intra- and inter-day precision values for quality assurance were in the ranges of 2.4-11 % and 2.5-11 %, respectively; bias ranged from - 2.6 % to 2.1 %. Blood serum levels of safrole, myristicin, and elemicin were measured at admission (approximately 8 h post-ingestion) and approximately 94 h after a post-admission fluid therapy to evaluate their biological half-lives. We developed this method to obtain information on the psychoactive constituents of nutmeg and, thereby, determine the toxicokinetic parameters of nutmeg in a case of nutmeg poisoning.

Acute acrylamide poisoning with severe symptoms in a short time: a case report.

BACKGROUND: Acrylamide poisoning is often reported as chronic poisoning presenting with peripheral neuropathy or carcinogenic action due to long-term exposure to low concentrations. However, there have been few reports of acute poisoning due to oral ingestion of acrylamide, where the symptoms appear a few hours after ingestion. Here, we report a case of acute acrylamide poisoning where a high concentration was ingested in a short time, resulting in a fatal outcome due to the rapid course of events. CASE PRESENTATION: The patient was an adolescent female who ingested 150 ml (148 g) of acrylamide with suicidal intent. A disorder of consciousness was observed when the emergency medical team arrived 36 min later. An hour later, tracheal intubation and intravenous access were performed at a hospital, and 2 h after that, she was transported to our hospital. After she arrived at the hospital, circulatory dynamics could not be maintained despite vasopressor and colloid osmotic infusion, and hemodialysis could not be introduced. Subsequently, cardiopulmonary arrest occurred, and the patient passed away 7 h after ingestion. In the present case, severe symptoms appeared shortly after acrylamide ingestion, unlike other reported cases. In previous report summarizing animal studies, there was a relationship among the symptoms of acute poisoning, the dose, and onset time. The data from this case were compared to those from previous reports, and we were able to predict the early appearance of severe symptoms based on this comparison. CONCLUSION: The severity of acute acrylamide poisoning by oral ingestion was primarily dependent on the amount and rate of ingestion.

Amatoxin poisoning caused by Galerina sulciceps, a species with no prior record of identification in Japan: a case report.

A 60-year-old man presented with acute gastroenteritis, hypovolemic shock, acute renal failure (BUN/Cr, 56.7/4.24 mg/dl), and aspiration pneumonia. The previous day, he ingested 30 caps of mushrooms of an unknown species. The patient was treated with a massive intravenous infusion, renal replacement therapy, and antimicrobial agents. Late-onset mild liver injury peaked on day 11 (AST/ALT, 62/67 IU/l). Acute renal failure improved once before worsening, with the worst symptoms on day 19 (BUN/Cr, 99/6.61 mg/dl). Thereafter, the patient showed gradual improvement, and renal replacement therapy was discontinued on day 23. His general condition improved fully and he was transferred to another hospital for rehabilitation on day 47. The mushrooms were later identified as Galerina sulciceps by the Basic Local Alignment Search Tool, and toxicologic analysis using liquid chromatography-tandem mass spectrometry revealed an average of 85 ppm α-amanitin and 330 ppm ß-amanitin in the tissue of the mushrooms brought in by the patient's family. Galerina sulciceps is distributed mainly in tropical and subtropical regions of Southeast Asia and had never been identified before in Japan. The heat of fermentation generated by the thick layer of wood chips on the ground or global warming may have contributed to its growth in Japan. Interestingly, our patient did not have liver dysfunction, which is one main and typical amatoxin poisoning symptom. Variation in clinical presentation may be attributed to the different ratios of α-amanitin to ß-amanitin in different mushroom species.

A suicide attempt by intramuscular injection of pentobarbital sodium into rectus abdominis suggested by computed tomography.

Suicide attempts in humans due to injections of the veterinary drug pentobarbital sodium have been rarely reported. Herein, we present a case of a suicide attempt by intramuscular injection of pentobarbital sodium into the rectus abdominis muscle, which was suggested by computed tomography (CT). A 73-year-old man was brought to the emergency department with GCS 3 (E1V1M1) and an incised wound on the right side of the neck. A bottle of Somnopentyl® (pentobarbital sodium, 64.8 mg/ml), a 20-ml empty syringe with an 18-mm needle, and no. 10 scalpel were present at the scene. At the emergency department, the patient was intubated and was admitted to the intensive care unit. A urine drug screen test by SIGNIFY® ER was positive for benzodiazepines and barbiturates, and continuous veno-venous hemofiltration (CHF) was initiated. The route of drug administration was initially unknown; however, a CT scan revealed swelling of the left rectus abdominis muscle with a wound suggestive of a needle puncture, and the CT analysis suggested 38.16 ml as the maximum dose of pentobarbital sodium. On day 3, the patient's consciousness improved, and he was weaned off CHF and mechanical ventilation. There have been several reports of postmortem CT yielding information on the site of administration of intoxicants, but there have been none for surviving intoxicated patients. This is the first report of the usefulness of CT to identify the site of administration of the causative agent of intoxication while the patient is still alive.

Severe caffeine poisoning successfully treated with high flow continuous hemodialysis.

In recent years, severe or lethal cases of caffeine poisoning after large or massive ingestion of caffeinated tablets have increased in Japan. Here we report the case of a 23-year-old male who ingested high-dose caffeine tablets (total: 32.4 g caffeine) in a suicide attempt. He was transferred to our hospital about 2 h after ingesting the tablets and presented with repeated vomiting and tremor in the trunk and extremities. His respiratory rate was 40 breaths/min, heart rate 240 beats/min, blood pressure 109/77 mmHg, and Glasgow Coma Scale E3V2M5. Blood tests revealed metabolic acidosis compensated with respiratory alkalosis, hyperlactatemia, hypokalemia, hyperglycemia, and leukocytosis. After tracheal intubation, gastric lavage was performed and activated charcoal was administered. The patient gradually became hypotensive (systolic blood pressure < 90 mmHg) with a heart rate > 250 beats/min, and non-sustained ventricular tachycardia frequently occurred. Given the lack of response to intravenous noradrenaline and landiolol, high flow continuous hemodialysis (CHD) was initiated 4 h after tablet ingestion with a blood flow rate of 150 mL/min and dialysate flow rate of 2000 mL/h. This dramatically improved his clinical signs and symptoms, especially during the first 3 h. His serum caffeine concentration was 240.9 µg/mL on admission and 344.0 µg/mL at the initiation of high flow CHD, but rapidly decreased to 153.8 µg/mL 3 h after initiating high flow CHD. Our findings suggest that high flow CHD may be effective in treating cases of severe caffeine poisoning with hemodynamics too unstable for intermittent hemodialysis.

Effectiveness of multiple-dose activated charcoal in lamotrigine poisoning: a case series.

INTRODUCTION: Lamotrigine toxicity can cause coma, seizures, and intraventricular conduction disturbances, and treatment options include good supportive care. We report two cases of lamotrigine poisoning in which multiple-dose activated charcoal may have shortened the elimination half-life of lamotrigine. CASE 1: A 21-year-old woman ingested 15.6 g lamotrigine, 14 g levetiracetam, and 15 mg clonazepam. She became comatose and developed generalized tonic seizure. One hour post-ingestion, 50 g activated charcoal was administered. Starting 11 h post-ingestion, 25 g activated charcoal was administered every 4 h for 4 doses. The peak concentration of serum lamotrigine was 49.5 µg/mL, and the elimination half-life after commencement of multiple-dose activated charcoal was 6.5 h. CASE 2: A 46-year-old woman ingested 0.3 g lamotrigine and 0.1 g topiramate twice, 2 h apart. She became drowsy, complained of blurred vision, vertigo, nausea, and vomited. An initial dose of 50 g activated charcoal was administered at 4.5 h post-second ingestion, and subsequent doses of 25 g (total of 3 doses) were administered every 4 h, commencing at 8.5 h post-second ingestion. The peak concentration of serum lamotrigine was 19.9 µg/mL, and the elimination half-life after commencement of multiple-dose activated charcoal was 9.3 h. DISCUSSION: The mean elimination half-life of lamotrigine in healthy volunteers and epileptic patients receiving lamotrigine monotherapy is 22.8-37.4 h. In our two cases, multiple-dose activated charcoal may have shortened the elimination half-life of lamotrigine, possibly by inhibiting enterohepatic circulation. Multiple-dose activated charcoal should be considered an option for treating lamotrigine poisoning.

Effectiveness of assertive case management for patients with suicidal intent.

The aim of this study was to examine the effectiveness of assertive case management intervention in preventing suicidal behaviour in self-poisoning patients. We conducted a secondary analysis of data from the ACTION-J study. Participants were self-poisoning patients with clear suicide intent admitted to emergency departments and with a primary psychiatric diagnosis (as per DSM-IV-TR axis 1). Patients were randomly assigned either to assertive case management or enhanced usual care. The primary outcome measure was the incidence of a first recurrent suicide attempt within 6 months. This study is registered at ClinicalTrials.gov (NCT00736918) and UMIN-CTR (C000000444). There were 297 self-poisoning patients in the intervention group and 295 in the control group. The primary outcome was significantly lower in the intervention group than in the control group. The incidence of a first recurrent suicide attempt within 1 and 3 months was also significantly lower in the intervention group, as was the number of overall self-harm episodes over the entire study period. Furthermore, the number of non-suicidal self-harm episodes and suicide attempts was significantly lower in the intervention group. Assertive case management is effective when promptly introduced in a hospital setting as an intervention following a suicide attempt, particularly for self-poisoning patients.

LC-MS/MS method for rapid and accurate detection of caffeine in a suspected overdose case.

Excessive intake of caffeine, otherwise known to be a safe and mild central nervous system stimulant, causes nausea, vomiting, convulsions, tachycardia, and eventually fatal arrhythmias and death. Caffeine intoxication, a global problem, has been increasing in Japan since 2013. Thus, there is a need for rapid and accurate diagnosis of caffeine poisoning in forensic and clinical toxicology investigations. Herein, we demonstrate rapid and accurate caffeine quantitation by liquid chromatography tandem mass spectrometry using the standard addition method in a fatal case. Biological samples were diluted 500-100,000-fold and subjected to a simple pretreatment (adding caffeine standard and internal standard and passing through a lipid removal cartridge). The multiple reaction monitoring transitions were 195 â†’ 138 for quantitation, 195 â†’ 110 for the qualifier ion, and 204 â†’ 144 for the internal standard (caffeine-d9). The standard plots were linear over 0-900 ng/mL (r2 = 0.9994-0.9999) for biological samples, and the reproducibility (%RSD) of the method was 1.53-6.97% (intraday) and 1.59-10.4% (interday). Fatal levels of caffeine (332 µg/mL) and toxic to fatal levels of olanzapine (625 ng/mL), along with other pharmaceuticals were detected in the external iliac venous blood. The cause of death was determined to be multi-drug poisoning, predominantly caused by caffeine. Our method is useful for not only forensic cases but also the rapid diagnosis of caffeine overdose in emergency clinical settings.