Relatively mild symptoms after chronic overdose with a double-dose encorafenib: a case report.

Encorafenib (Braftovi) is indicated for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation, in combination with binimetinib (Mektovi). According to the product label of encorafenib, there are no specific treatment recommendations in case of an overdose. We report on a 63-year-old man who ingested a double dose (900 mg) of encorafenib for 16 days. He developed overall minor chronic overdose symptoms such as nausea and vomiting grade 1 and muscle pain. Based on the most occurring adverse events of encorafenib, liver values, kidney function parameters and QTc interval were measured. Kidney function parameters were normal, whereas liver values were slightly increased (grade 1) and QTc slightly prolonged. The plasma concentration 3 h after the last dose was 2110 ng/mL. We describe the course of a case with a chronic overdose during 16 days of the double dose of encorafenib as well as the followed approach, which could be taken into account when observing an encorafenib overdose. Providing information in times of Covid-19 is challenging, but remains necessary for good clinical care.

Paracetamol overdose in the newborn and infant: a life-threatening event.

PURPOSE: Paracetamol is the only drug recommended to treat fever in neonates. At recommended doses, paracetamol has not been associated with liver injury in neonates, while hepatotoxicity may occur after intake of a single high dose or multiple excessive doses. The aim of this narrative review is to critically analyze and summarize the available literature on newborns and infants exposed to supratherapeutic doses of paracetamol, with special focus on their clinical features, outcome, and management. METHODS: The PubMed, SCOPUS, and Google Scholar search engines were used to collect data, without time limitation. The following keywords were used: paracetamol/acetaminophen, overdose, hepatotoxicity, N-acetylcysteine, newborn, infant. RESULTS: The literature search identified a total of 27 case reports, a number of review articles, and few other relevant publications. Neonatal poisoning from paracetamol resulted from transplacental drug transfer after maternal overdose in some published cases, while it was the consequence of medication errors in other cases. Newborns and infants who have received a single overdose and have paracetamol concentrations below the Rumack-Matthew nomogram limits are at low risk of serious hepatic damage, while those who have recently ingested more than one supratherapeutic dose of paracetamol should be managed with caution. The treatment of choice for paracetamol poisoning is N-acetylcysteine, a specific antidote which reduces paracetamol hepatotoxic effects. N-Acetylcysteine should be given according to specific regimens through weight-based dosing tables. CONCLUSIONS: Caution should be used when paracetamol is administered to the newborn. In the event of an overdose, careful patient monitoring and personalization of post-overdose procedures are recommended.

Unintentional Infiltration of High Dose Epinephrine in an Infant: A Case Report.

Verbal orders in the operating room between the surgeon and circulating nurse are prevalent at many institutions. We present a case in which a communication breakdown involving a verbal order resulted in the patient receiving an excessively high dose of epinephrine via subcuticular infiltration. The overdose was quickly identified by an increase in T-wave amplitude on electrocardiogram (ECG). The hemodynamic changes were treated, and the patient suffered no long-term sequelae. This report emphasizes the need to have strategies in place to prevent medication errors.

Clinical outcomes after colchicine overdose: A case report.

RATIONALE: Colchicine can inhibit cell division and intracellular transport in affected organs by fixing intracellular tubulin and preventing its polymerization into microtubules. A lethal dose of colchicine is considered to be 0.8 mg/kg. The wide distribution of colchicine through 70% of the body following an overdose makes it difficult to eliminate. PATIENT CONCERNS: A 56-year-old man with a clear history of colchicine overdose was admitted to our hospital nearly 40 hours after taking 12 mg (0.17 mg/kg) of colchicine. He had a history of gout and chronic kidney disease. As the disease progressed, he showed most of the clinical manifestations and pathological features of colchicine overdose. DIAGNOSES AND INTERVENTIONS: Colchicine overdose was clear, with symptoms of multiple organ failure including primary gastrointestinal failure, bone marrow hematopoietic inhibition, rhabdomyolysis, cardiac damage, hepatocyte damage. The patient developed secondary septic shock, renal failure, circulatory failure, and respiratory failure. We performed continuous renal replacement therapy and gastric lavage, and administered norepinephrine, frozen plasma, proton-pump inhibitors, adenosylmethionine, antibiotics, granulocyte colony stimulating factor, and total parenteral nutrition. OUTCOMES: The patient rapidly developed complete hematopoietic function inhibition, gastrointestinal failure, and cardiac damage 32 hours after admission. Sustained severe infection and circulatory instability caused a progressive deterioration of respiratory function. Tracheal intubation was performed but the patient continued to deteriorate, and death occurred approximately 132 hours after admission. LESSONS: Excessive colchicine levels cause continuous organ damage due to extensive tissue distribution, eventually leading to multiple organ failure. Colchicine metabolism is delayed in patients with liver or kidney dysfunction, and even a low dose of colchicine may result in poisoning in these individuals. Early diagnosis and reduction of colchicine levels is critical to improve prognosis, and colchicine poisoning should be considered in patients with poor liver or kidney function even when the ingested dose is low.

Haemodiafiltration as an effective treatment option for massive paracetamol overdose.

An 84-year-old woman presented to hospital with severe clinical and metabolic sequelaesequelae of a massive paracetamol overdose (concentration=822 mg/L). In spite of N-acetylcysteine therapy, she deteriorated with evidence of mitochondrial dysfunction. Although the EXtracorporeal TReatments In Poisoning group recommend adjunct haemodialysis (HD) in such a context, this was difficult to start due to haemodynamic instability. Instead, a trial of continuous venovenous haemodiafiltration (CVVHDF) was initiated in an attempt to restore normal mitochondrial function, normal pH and to actively remove the offending drug. Fortunately, plasma paracetamol levels fell exponentially over the subsequent 24-48 hours without the need to commence HD. The patient made a full recovery and was later discharged from the hospital. This case highlights that CVVHDF can be a reasonable alternative to HD for managing massive paracetamol overdoses in the context of mitochondrial dysfunction.

Lacosamide Overdose: A Case of QRS Prolongation and Seizure.

BACKGROUND: Lacosamide is a third-generation antiepileptic drug. Its likely mechanism of action is via neuronal sodium channel blockade, via a unique manner compared with other antiepileptic drugs that block sodium channels. A paucity of information exists regarding lacosamide overdosage. Lacosamide overdosage is thought to cause QRS prolongation and seizures, due to its effect of sodium channel blockade. The potential efficacy of sodium bicarbonate to reverse the effects of lacosamide has not been well studied. Furthermore, prior reports of lacosamide toxicity have occurred in the setting of concomitant polypharmacy. Thus, the isolated toxic effects of the drug have not been well elucidated. CASE REPORT: We report a case of a suspected, single-ingestion overdose on lacosamide. The patient developed signs of cardiotoxicity and seizure. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: After lacosamide overdosage, the emergency physician must be capable of acute management of subsequent lacosamide toxicity. Understanding the mechanisms of action causing toxicity due to this drug can help the clinician to anticipate the interventions that may be needed or useful to treat this potentially toxic ingestion.

Intoxicación por ácido acetilsalicílico, fisiopatología y manejo / Physiopathology and management of acetylsalicylic acid intoxication

Acetylsalicylic acid (ASA) intoxication is potentially lethal. After ingestion, AAS is rapidly transformed into salicylic acid that dissociates into an hydrogen ion plus salicylate. Salicylate is the main form of AAS in the body and produces multiple alterations. Initially, the stimulation of the ventilatory center promotes a respiratory alkalosis. Then, the mitochondrial dysfunction induced by salicylate, will generate a progressive metabolic acidosis due to the accumulation of ketoacids, lactic acid and dicarboxylic acids among others. Another alterations include hydro electrolytic disorders, gastrointestinal lesions, neurological involvement, ototoxicity and coagulopathy. The correct handling of acetylsalicylic acid intoxication requires an thorough knowledge of its pharmacokinetics and pharmacodynamics. Treatment consists in life support measures, gastric lavage, activated charcoal and urinary alkalization to promote the excretion of salicylates. In some occasions, it will be necessary to start renal replacement therapy as soon as possible.

Bilateral sciatic neuropathy with severe rhabdomyolysis following venlafaxine overdose: A case report.

RATIONALE: Venlafaxine is an antidepressant and anxiolytic agent that functions by inhibiting central serotonin and norepinephrine reuptake, and it is a relatively recently introduced drug. In particular, overdose of venlafaxine has been reported to cause severe cardiac toxicity including ventricular tachycardia, prolongation of QT interval, and seizure or severe muscular injury. However, reports describing venlafaxine-induced rhabdomyolysis with neuropathy remain scarce. Accordingly, we report such a case involving a 49-year-old woman with bilateral sciatic neuropathy combined with rhabdomyolysis following venlafaxine overdose. PATIENT CONCERNS: The patient complained of severe pain and tenderness in both thighs, weakness in both ankle flexor and extensor muscles, and a tingling sensation in the toes of both feet. DIAGNOSES: Bilateral sciatic neuropathy combined with rhabdomyolysis following venlafaxine overdose. INTERVENTION: Needle electromyography revealed fibrillation potentials and positive sharp waves, with absent recruitment in all the major muscles innervating the sciatic nerve bilaterally. Pelvic magnetic resonance imaging was performed after electromyography and revealed multifocal enhancement of signal intensity, suggesting muscle necrosis in the gluteus and thigh muscles, and swelling of both sciatic nerves on short tau inversion recovery (STIR) imaging sequences. OUTCOMES: Two months later, the patient's ankle dorsiflexion strength, measured with manual muscle test, was grade 0/0, and ankle plantar flexion was grade 0/0. The patient reported little sensation at the lateral and posterior aspects of her lower leg, and dorsum and sole of the foot. A follow-up electromyography study revealed improvement in the long head of the right biceps femoris; polyphasic motor unit action potentials with diminished recruitment were observed, but otherwise unchanged. LESSONS: When encountering patients who have overdosed on venlafaxine, it is very important to detect and treat severe complications such as cardiac toxicity, seizure, and rhabdomyolysis, among others. However, if rhabdomyolysis has already materialized, it should not be forgotten that the secondary damage caused by it. Physicians should rapidly detect and be minimized to mitigate future complications.

Overdoses with Aripiprazole: Signs, Symptoms and Outcome in 239 Exposures Reported to the Danish Poison Information Centre.

The aim of this study was to characterize the clinical signs and symptoms of exposures to aripiprazole overdoses. We retrospectively identified all aripiprazole exposures reported to the Danish Poison Information Centre (DPIC) from June 2007 to May 2015. Information concerning demographics, ingested dose and symptoms was extracted from the DPIC database and medical records. Information on death and admission to hospital was obtained from Danish national registers. We analysed 239 cases, 86 concerning single-drug exposures to aripiprazole, and 153 cases where aripiprazole had been taken with at least one other substance (mixed-drug). The median ingested aripiprazole dose was 105 mg (IQR: 50-1680 mg) in the single-drug exposure group and 120 mg (IQR: 60-225 mg) in the mixed-drug exposure group. The most commonly reported symptom was light sedation, reported in 63% of the single-drug group and 50% of the mixed-drug exposure group. There were no malignant arrhythmias or ECG abnormalities after single-drug exposures. No deaths were recorded in relation to the intake. We found a long-term mortality rate of 13 deaths per 1000 person-years (95% CI: 7; 23 per 1000 person-years), which is significantly higher than in an age- and gender-matched background population. In conclusion, we found that aripiprazole overdoses had few and mild symptoms predominantly related to the sedative properties. We detected a benign cardiovascular safety profile and no new safety concerns. Our findings may support an increased threshold of 300 mg for hospital admission after a single-drug exposure with aripiprazole and symptoms not worse than light sedation.

Interaction among hERG channel blockers is a potential mechanism of death in caffeine overdose.

Caffeine overdose death is due to cardiac arrest, but its mechanism has not been explored in detail. In this study, our data showed that caffeine significantly prolonged the heart rate-corrected QT interval (QTc) of rabbits in vivo (P<0.05; n=7). Caffeine was also found to be a hERG channel blocker with an IC50 of 5.04mM (n=5). Although these two findings likely link caffeine overdose death with hERG channel blockade, the amount of caffeine consumption needed to reach the IC50 is very high. Further study demonstrated that addition another hERG blocker could lower the consumption of caffeine significantly, no matter whether two hERG blockers share the same binding sites. Our data does not rule out other possibility, however, it suggests that there is a potential causal relationship between caffeine overdose death with hERG channel and the interaction among these hERG blockers.

Lack of respiratory depression in paracetamol-codeine combination overdoses.

AIMS: Codeine containing analgesics are commonly taken in overdose, but the frequency of respiratory depression is unknown. We investigated whether paracetamol-codeine combination overdoses caused respiratory depression more than paracetamol alone. METHODS: We reviewed deliberate self-poisoning admissions with paracetamol (>2 g) and paracetamol-codeine combinations presenting to a tertiary toxicology unit (1987-2013). Demographic information, clinical effects, treatment (naloxone, length of stay [LOS], mechanical ventilation) were extracted from a prospective database. Primary outcome was naloxone requirement or ventilation for respiratory depression. RESULTS: From 4488 presentations, 1376 admissions were included with paracetamol alone (929), paracetamol-codeine combinations (346) or paracetamol-codeine-doxylamine combinations (101) without co-ingestants. Median age was 23 years (12-89 years); 1002 (73%) were female. Median dose was 12 g (interquartile range [IQR]: 7.5-20 g). Median LOS was 16 h (IQR: 6.5-27 h) and 564 (41%) were given acetylcysteine. Significantly larger paracetamol doses were ingested and more acetylcysteine given in paracetamol alone versus paracetamol combination overdoses. Seven out of 1376 patients were intubated or received naloxone (0.5%; 95% CI: 0.2-1.1%), three intubated, three given naloxone and one both. Three out of 929 patients ingesting paracetamol alone (0.3%; 95% CI: 0.1-1%) required intubation or naloxone, compared to two out of 346 ingesting paracetamol-codeine combinations (0.6%; 95% CI: 0.1-2.3%; absolute difference, 0.26%; 95% CI: -0.7-1.2%; P = 0.62). Two out of 101 patients ingesting paracetamol-codeine-doxylamine combinations (2%; 95% CI: 0.3-8%) required intubation or naloxone. Four patients were intubated for reasons other than respiratory depression: hepatotoxicity (2), retrieval (1), no data (1). Two out of 929 (0.2%) paracetamol alone overdoses had a Glasgow coma score < 9 compared to three out of 346 (0.9%) in the paracetamol-codeine group. CONCLUSIONS: Paracetamol-codeine combination overdoses are rarely associated with severe respiratory depression, with only two given naloxone and none intubated for respiratory depression.

Two Cases of Refractory Cardiogenic Shock Secondary to Bupropion Successfully Treated with Veno-Arterial Extracorporeal Membrane Oxygenation.

Bupropion inhibits the uptake of dopamine and norepinephrine. Clinical effects in overdose include seizure, status epilepticus, tachycardia, arrhythmias, and cardiogenic shock. We report two cases of severe bupropion toxicity resulting in refractory cardiogenic shock, cardiac arrest, and repeated seizures treated successfully. Patients with cardiovascular failure related to poisoning may particularly benefit from extracorporeal membrane oxygenation (ECMO). These are the first cases of bupropion toxicity treated with veno-arterial EMCO (VA-ECMO) in which bupropion toxicity is supported by confirmatory testing. Both cases demonstrate the effectiveness of VA-ECMO in poisoned patients with severe cardiogenic shock or cardiopulmonary failure.

Modern Intermittent Haemodialysis (IHD) is an Effective Method of Removing Salicylate in Chronic Topical Salicylate Toxicity.

INTRODUCTION: There are limited data on modern intermittent hemodialysis (IHD) efficacy on salicylate elimination from topical poisoning. CASE REPORT: A 54-year-old male sought treatment for dyspnea but was then diagnosed with salicylate toxicity from topical application of Dencorub Extra Strength Heat Gel® for 1 week. Each tube contained 100 g with 26 % methylsalicylate (26 g). Laboratory workup was remarkable for an elevated anion gap of 30 and salicylate concentration of 78.7 mg/dL [5.7 mmol/L (N < 0.4 mmol/L)]. Treatment with urinary alkalinization was followed by hemodialysis for 5 h. Extraction ratios were 0.44 with clearance rates of 78.5 mL/min. Salicylate concentrations fell rapidly following initiation of hemodialysis with no rebound observed. DISCUSSION: Modern high flux IHD is an effective method of removing salicylates in the treatment of chronic topical poisoning.

Understanding Heroin Overdose: A Study of the Acute Respiratory Depressant Effects of Injected Pharmaceutical Heroin.

Opioids are respiratory depressants and heroin/opioid overdose is a major contributor to the excess mortality of heroin addicts. The individual and situational variability of respiratory depression caused by intravenous heroin is poorly understood. This study used advanced respiratory monitoring to follow the time course and severity of acute opioid-induced respiratory depression. 10 patients (9/10 with chronic airflow obstruction) undergoing supervised injectable opioid treatment for heroin addiction received their usual prescribed dose of injectable opioid (diamorphine or methadone) (IOT), and their usual prescribed dose of oral opioid (methadone or sustained release oral morphine) after 30 minutes. The main outcome measures were pulse oximetry (SpO2%), end-tidal CO2% (ETCO2%) and neural respiratory drive (NRD) (quantified using parasternal intercostal muscle electromyography). Significant respiratory depression was defined as absence of inspiratory airflow >10s, SpO2% < 90% for >10s and ETCO2% per breath >6.5%. Increases in ETCO2% indicated significant respiratory depression following IOT in 8/10 patients at 30 minutes. In contrast, SpO2% indicated significant respiratory depression in only 4/10 patients, with small absolute changes in SpO2% at 30 minutes. A decline in NRD from baseline to 30 minutes post IOT was also observed, but was not statistically significant. Baseline NRD and opioid-induced drop in SpO2% were inversely related. We conclude that significant acute respiratory depression is commonly induced by opioid drugs prescribed to treat opioid addiction. Hypoventilation is reliably detected by capnography, but not by SpO2% alone. Chronic suppression of NRD in the presence of underlying lung disease may be a risk factor for acute opioid-induced respiratory depression.

Bupropion Overdose Presenting as Status Epilepticus in an Infant.

BACKGROUND: Bupropion is a monocyclic antidepressant in the aminoketone class, structurally related to amphetamines. The Food and Drug Administration withdrew this product from the market in 1986 after seizures were reported in bulimic patients. It was later reintroduced in 1989 when the incidence of seizures was shown to be dose-related in the immediate release preparation. Massive bupropion ingestion has been associated with status epilepticus and cardiogenic shock in adults. Seizures have been reported in children, but not status epilepticus. This report highlights a patient who presented with status epilepticus and developed cardiopulmonary arrest after bupropion ingestion. False-positive amphetamine diagnosis from urine drug screen on presentation was reported. METHOD: We review the presentation, clinical course, diagnostic studies, and outcome of this patient. We then review the literature regarding bupropion overdose in children. RESULT: Symptoms of bupropion toxicity and risk for seizures are dose-dependent and fatalities have been reported. Our patient developed status epilepticus and cardiopulmonary arrest and then progressed to have a hypoxic ischemic encephalopathy and refractory symptomatic partial seizures. CONCLUSION: Our report highlights the need to keep this medication away from children in order to prevent accidental overdose.

Ritualistic Use of Ayahuasca versus Street Use of Similar Substances Seized by the Police: A Key Factor Involved in the Potential for Intoxications and Overdose?

The ritualistic use of ayahuasca is becoming a global phenomenon. This beverage contains a combination of monoamine oxidase inhibitors (harmine, harmaline, and tetrahydroharmine) and N,N-dimethyltryptamine, the main substance responsible for its visionary effect. The recreational use of similar alkaloids and N,N-dimethyltryptamine has increased in recent years, mainly because of their hallucinogenic effects. In the present study, the concentrations of psychoactive alkaloids in three powder samples seized by the São Paulo State Police and nine ayahuasca aqueous extracts were analyzed by HPLC-DAD in an attempt to distinguish between illicit drugs and the religious beverage. The alkaloids detected (µg/mL) in the ayahuasca aqueous extracts were N,N-dimethyltryptamine (402-2070.3), harmaline (27.5-181.3), harmine (294.5-2893.8), and tetrahydroharmine (849.5-2052.5), whereas, of the three powder samples, one contained only N,N-dimethyltryptamine (82% and 2% w/w, respectively) while the other contained only harmaline (16%, w/w) and harmine (12%, w/w). The ritualistic use of ayahuasca involves oral intake and the probability of overdose is minimized by serotonergic stimulation of vagal pathways, leading to vomiting and diarrhea. In contrast, the recreational use of N,N-dimethyltryptamine involves consumption mainly by smoking or inhalation, both of which markedly increase its bioavailability and the potential for intoxications.

Massive Atenolol, Lisinopril, and Chlorthalidone Overdose Treated with Endoscopic Decontamination, Hemodialysis, Impella Percutaneous Left Ventricular Assist Device, and ECMO.

BACKGROUND: Overdose of cardiovascular medications is increasingly associated with morbidity and mortality. We present a case of substantial atenolol, chlorthalidone, and lisinopril overdose treated by multiple modalities with an excellent outcome. CONCLUSION: Aggressive medical intervention did not provide sufficient hemodynamic stability in this patient with refractory cardiogenic and distributive shock. Impella® percutaneous left ventricular assist device and extracorporeal membrane oxygenation provided support while the effects of the overdose subsided. We present concentrations demonstrating removal of atenolol with continuous venovenous hemodiafiltration. This is the first report of esophagogastroduo denoscopy decontamination of this overdose with a large pill fragment burden.