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.

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.

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.

Effect of Suvorexant on Nocturnal Delirium in Elderly Patients with Alzheimer's Disease: A Case-series Study.

Suvorexant, an orexin receptor antagonist used for insomnia, has been shown to have a preventive effect on delirium in a randomized placebo-controlled trial. However, its effectiveness in the management of nocturnal delirium has not yet been determined. Here we report four cases in which elderly patients with moderate to severe Alzheimer's disease who developed nocturnal delirium were treated with suvorexant. In case 1, 15 mg suvorexant was initiated to manage nocturnal delirium refractory to antipsychotics, antidepressants, and a Japanese herbal medicine, resulting in immediate sleep improvement. However, treatment discontinuation led to recurrence of symptoms, which were reversed by recommencing suvorexant. In case 2, as antipsychotics used for the treatment of nocturnal delirium were ineffective, 15 mg suvorexant was administered. The patient achieved rapid improvement in sleep. In case 3, the use of atypical antipsychotics for the treatment of nocturnal delirium was contraindicated, as the patient had diabetes. Therefore, 15 mg suvorexant was administered following good outcomes in cases 1 and 2, resulting in immediate sleep improvement. Finally, in case 4, 15 mg suvorexant was used as an initial medication for nocturnal delirium, and the patient showed sleep improvement immediately. Elevated orexin levels in the cerebrospinal fluid are reportedly linked to sleep deterioration in patients with moderate to severe Alzheimer's disease. The immediate and reproducible action and effectiveness of suvorexant observed in our patients suggest that enhanced cerebral orexin activity might be associated with sleep-wake cycle disturbances due to delirium in elderly patients with Alzheimer's disease.

A fast paraquat quantitation method in human serum using probe electrospray ionization-tandem mass spectrometry for emergency settings.

INTRODUCTION: Paraquat (PQ) is one of the most toxic herbicides to humans. However, it is still in use in many countries, including Japan, and many incidents, such as homicides, intentional ingestions, and occupational accidents, have been reported thus far. In PQ poisoning cases, it is possible to predict severity and prognosis using nomograms. Therefore, if the serum PQ level is determined immediately, a treatment plan can be rapidly established. However, most known analytical methods are time-consuming and therefore hardly ever contribute to patient treatment. METHODS: We developed a new method for PQ quantitation in serum by combining a probe electrospray ionization technique with mass spectrometry. This method requires virtually no serum pretreatment and can yield quantitation values in 18 s. RESULTS: We applied the proposed method to samples from real poisoning cases and compared the results with those obtained via liquid-chromatography-tandem mass spectrometry, revealing the absence of any significant differences at the 5% significance level (t(8) = 1.000, p > .05). The limits of detection and quantitation were 0.004 and 0.015 µg/L, respectively, and the calibration curve exhibited good linearity over the concentration range of 0.015-4.0 µg/mL (r2 = 0.998). DISCUSSION: As the proposed method is fast and easy to perform, it should be useful in emergency medical settings.

An ultra-rapid drug screening method for acetaminophen in blood serum based on probe electrospray ionization-tandem mass spectrometry.

Poisoning incidents caused by drugs, accidental ingestion of poisons, attempted suicide, homicide, and exposure to toxic compounds occur frequently every year across the globe. This raises the need to rapidly identify toxic agents in poisoned patients in a clinical emergency setting. In addition, determining drug/poison concentration is undoubtedly necessary to arrive at a toxicological treatment plan. The purpose of this study was to develop an ultra-rapid drug screening method for the clinical treatment of poisoning. Probe electrospray ionization (PESI), one of the ambient ionization techniques, is able to detect compounds from various biological materials almost directly. We applied the PESI technique to the rapid detection of acetaminophen (APAP). Blood serum samples were diluted 100-fold with 10 mM ammonium formate/ethanol (1:1 v/v) solution including deuterium-labeled internal standards (IS; APAP-d4). Only 10 µL of the diluted sample was used for measurement. The tandem mass spectrometer (MS/MS) equipped with a PESI was used in selected reaction monitoring mode for the quantitation of APAP; the measurement time was only 18 s. Transitions were set at 152 > 110 for quantitation, 152 > 65 for qualifier, and 156 > 114 for IS (APAP-d4). All measurements were conducted in positive mode. The calibration curve (1/x2) was linear over the range of 1.56-200 µg/mL (r2 = 0.998), and the limit of detection and quantitation were 0.37 µg/mL and 1.56 µg/mL, respectively. The accuracy (bias) and precision (RSD%) of the method were within an acceptable range (-0.15-2.8% and 2.3-6.1%, respectively) and matrix effect at 3 concentrations (95.1-104%) indicated that PESI-MS/MS is only slightly affected by matrices. In real forensic cases, quantitative values of APAP determined by the PESI-MS/MS were almost identical to those determined by the liquid chromatography-MS/MS method. Since PESI-MS/MS is a simple, reliable, and rapid determination method for toxic agents with virtually no need for blood serum pre-treatment, it would be highly suitable for poisoning cases in clinical emergency settings. In the future, a method for simultaneous rapid determination of multiple toxic agents will be developed.

Application of probe electrospray ionization-tandem mass spectrometry to ultra-rapid determination of glufosinate and glyphosate in human serum.

Glufosinate and glyphosate, which are non-selective herbicides that include an amino acid moiety in their structures, are frequently used worldwide to control unwanted vegetation. Unfortunately, these readily available herbicides are also used by people to commit suicide, and thus represent important chemicals of interest in the fields of clinical medicine and forensics. Because of the high water solubility of these herbicides, most analytical methods for their detection require a derivatization step, which results in longer analysis times. Therefore, derivatization-based methods do not currently contribute to judgements on treatment decisions in emergency medicine. In this study, we addressed this limiting factor by developing an ultra-rapid and simple analytical technique using a combination of probe electrospray ionization (PESI) and tandem mass spectrometry (MS/MS), which gives quantitative results within 0.3 min. Herbicide standards were added to human serum that was then subjected to analysis (N = 5 per concentration). The analysis was repeated daily over eight consecutive days. The limit of detection (LOD) was 0.59 µg/mL for glufosinate and 0.20 µg/mL for glyphosate. The limit of quantitation (LOQ), i.e., the lowest point on the calibration curves, was 1.56 µg/mL for both the herbicides. The matrix effects were observed at three different concentrations (between 95.7%-104% for glufosinate, and between 90.7%-95.7% for glyphosate). When applied to samples taken from actual poisoning cases (six samples for each herbicide), the present method gave almost the same quantitative values as those obtained by conventional high-performance liquid chromatography with fluorescence detection. Thus, we believe that PESI-MS/MS could emerge as a rapid diagnosis method in the clinical emergency field.

Mild manifestation of methanol poisoning half a day after massive ingestion of a fuel alcohol product containing 70% ethanol and 30% methanol: a case report.

CASE: Is fomepizole necessary after massive ingestion of a mixture of methanol and ethanol? We report the case of a 37-year-old man who was transported to our Poison Center 12 h after ingesting 500 mL of fuel alcohol containing 70% methanol and 30% ethanol in a suicide attempt. On admission, he presented only with somnolence and mild metabolic acidosis. We hypothesized that most of the ethanol had been metabolized. OUTCOME: As the estimated serum concentration of methanol was lethal (242.6 mg/dL), fomepizole was given i.v. and hemodialysis was carried out twice, resulting in complete recovery. Later, the serum concentrations of both methanol and ethanol on admission were found to be 224.1 and 0.51 mg/dL, respectively. CONCLUSION: Therapeutic intervention was delayed by half a day after ingestion of a product containing methanol and ethanol in the present case. If the patient had arrived earlier, he may have only been treated with hemodialysis, but not fomepizole.

Direct detection of the psychoactive substance MT-45 in human tissue samples by probe electrospray ionization-tandem mass spectrometry.

Analyses of drugs and poisons in tissue samples are essential in forensic toxicology and pharmacology. However, current procedures for tissue analysis are laborious and time-consuming. Therefore, we assessed the utility of a newly devised probe electrospray ionization (PESI) technique with tandem mass spectrometry (MS/MS) for easy, ultra-rapid drug detection in human tissue samples. Using this system, typical pretreatment procedures, such as solid-phase extraction, liquid-liquid extraction, deproteinization, or homogenization, can be avoided. Briefly, a tissue sample of 1-2 mm3 was supplemented with a solution of ethanol and 10 mmol/L ammonium formate, and measurements were obtained. We demonstrated the successful application of this method in a forensic case by detecting an opioid analgesic, MT-45, in all tissue samples (liver, kidney, lung, brain, and heart). We also detected oxidized metabolites of MT-45 in the liver. Since the analysis required only 0.5 minutes per sample, PESI-MS/MS is an ultra-rapid detection method. Furthermore, for a quantitative approach, the total analysis time for the combination of PESI-MS/MS with the quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction method (from instrument start-up to extraction and PESI-analysis) was within 8 minutes. MT-45 concentrations obtained by QuEChERS-PESI-MS/MS and liquid chromatography (LC) -MS/MS were similar for all tissue samples. PESI-MS/MS cannot be used to separate isobars/isomers (ie, compounds with the same m/z value), similar to other direct introduction techniques. Further studies are needed to validate the quantitation method. However, our results indicate that PESI-MS/MS is a potentially easy and rapid technique for the analysis of drugs and poisons in human tissue samples.