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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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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.

Rationale: Vortioxetine is a new multimodal antidepressant approved by the Food and Drug Administration for the treatment of Major Depressive Disorder and recently introduced in Europe. While antidepressant properties of vortioxetine and its tolerability have been demonstrated by preclinical and clinical studies data on the safety of vortioxetine after overdose are still lacking., Patient Concerns: A 50-year-old Caucasian man presenting a severe depressive episode that in a suicide attempt he took vortioxetine at 250 mg., Diagnoses: Suicide attempt by vortioxetine in a patient affected by Major Depressive Disorder., Interventions: General evaluations and gastric lavage with 2 L of water plus 50 g of activated charcoal was performed. After 12 hours of clinical stability, the patient was discharged from the emergency department and considering the suicidal ideation he was admitted to the inpatients psychiatric department., Outcomes: After vortioxetine overdose the patient displayed no clinical signs or symptoms resulting from the exposure suggesting a good safety in overdose., Lesson: Overdose safety of different antidepressant drugs is a matter of great considering that overdose in individuals affected by Major Depressive Disorder frequently involves prescribed antidepressants. Previous studies showed wide variation in the relative toxicity of different antidepressant drugs with higher toxicity for tricyclic antidepressants, followed by venlafaxine bupropion and mirtazapine and lower for selective serotonin reuptake inhibitors. By now there is limited clinical trial experience regarding human overdose with vortioxetine and the maximum single dose tested was 75 mg in men associated with increased rates of nausea, dizziness, diarrhea, abdominal discomfort, generalized pruritus, somnolence, and flushing. Even if there is still limited available evidence and further investigation is needed to better understand the potential risk of vortioxetine overdose; from our case, it seems that vortioxetine overdose at 250 mg (12 times the common daily dose) showed no signs or symptoms resulting from the exposure suggesting a good safety in overdose.

We report a 34-year-old woman who developed clinical botulism after the cosmetic use of an unapproved botulinum toxin type A. Electrophysiologic findings demonstrated complete denervation with complete electrical silence. She had a lengthy recovery but was able to ambulate by discharge.

Objectives: To quantify the association of HIV infection with overdose mortality and explore the potential mechanisms., Design: A prospective cohort study., Methods: A total of 1927 actively injecting drug users who were HIV seronegative at baseline, of whom 308 later HIV seroconverted, were followed semi-annually for death from 1988 to 2001. Survival analyses using marginal structural and standard Cox models were used to evaluate the effect of HIV infection on the risk of overdose mortality., Results: Overdose death rates were higher in HIV-seropositive than HIV-seronegative drug users: 13.9 and 5.6 per 1000 person-years, respectively (P < 0.01). The hazard ratio (HR) was 2.54 [95% confidence interval (CI) 1.47, 4.38] for the marginal structural model and 2.06 (95% CI 1.25, 3.38) for the standard Cox model, both adjusted for demographics, drug injection characteristics, alcohol abuse, substance abuse treatment, and sexual orientation. Adjusting for possible time-varying mediators (i.e. drug use, medical conditions and healthcare access) in extended marginal structural models reduced the effect of HIV on overdose mortality by 30% (HR 1.82, 95% CI 1.01, 3.30). Abnormal liver function was associated with a higher risk of overdose mortality (HR 2.00, 95% CI 1.05, 3.84); adjustment for this further reduced the effect of HIV on overdose mortality., Conclusion: HIV infection was associated with a higher risk of overdose mortality. Drug use behavior, systematic disease and liver damage associated with HIV infection appeared to account for a substantial portion of this association. The data suggest a group to target with interventions to reduce overdose mortality rates.

Objective: Cocaine, which first made its appearance >1,000 yrs ago, is now widely used throughout the world. The physiologic responses to cocaine may cause severe pathologic effects. This review highlights the many critical care challenges resulting from these effects., Design: Historical vignettes, epidemiologic factors, modes of preparation and delivery, and the physiologic and pharmacologic effects of these agents are presented., Setting: Cocaine causes intense vasoconstriction, which potentially causes damage to all organ systems. Examples of these toxicities are presented., Patients: The adverse multisystem responses to cocaine exposure produce organ failure, which challenges diagnostic accuracy and therapeutic intervention. Organ system failure involves the brain, heart, lung, kidneys, gastrointestinal tract, musculature, and other organs. These harmful effects are additive to preexisting organ dysfunction., Intervention: Recognition of associated cocaine injury alerts the physician that organ dysfunction is more likely to occur and to be more severe. Such anticipation helps plan for therapy in the critical care setting., Results and Conclusions: Cocaine use is an expanding health hazard, despite intense governmental efforts to contain its distribution and use. Recognition of the signs and symptoms of cocaine toxicity help anticipate the subsequent organ dysfunction and implement earlier organ system support.

Objective: The aim of the present study was to test whether circadian differences in the response to opiates exist in humans and, if so, whether they are synchronized with the well-known circadian variations in overdose frequency., Design: Daily variations in opiate overdose frequency, total amount of naloxone necessary to treat the comatose state, and frequency of hospitalization were examined in pure, nonlethal, consecutive cases of opiate (presumably intravenous heroin) overdoses. Furthermore, daily variations in the frequency of lethal overdoses were examined in all cases observed during the same period., Setting: An 8-yr prospective, observational study in the city and suburban area of Ferrara, Italy., Patients: A total of 518 consecutive cases of nonlethal opiate overdoses in 327 different patients, plus 110 consecutive cases of lethal opiate overdoses with precise or presumptive time of death., Results: Analysis of the circadian distribution of nonlethal overdoses showed a significant peak in the afternoon to early evening. Analysis of the distribution of the hourly average amount of naloxone used to rescue patients from coma showed an opposite circadian variation, with a significant peak in the early morning. The hospitalization risk was also significantly higher from 3:00 to 8:59 am. However, in a subset of representative cases, plasma morphine concentrations did not change significantly in different hours of the day. Analysis of circadian distribution of lethal overdoses showed a significant peak in the evening hours. The death risk (calculated as the percentage of lethal events in the total number of intoxications within a given time frame) was significantly higher from 3:00 to 8:59 am., Conclusion: The present data provide evidence for the existence of circadian variations in the individual sensitivity to opiate overdose.

Patients with cyanide exposure present a rare and unique challenge to the critical care nurse. The following article assists the critical care nurse and advanced practice nurse in understanding the pathophysiology of cyanide exposure, assessment of signs and symptoms, and antidotal and supportive therapies. In addition, a case review of nursing care for a patient exposed to cyanide is discussed.

Sertraline (Zoloft) is a selective serotonin reuptake inhibitor that is commonly used in adults in the treatment of mood and anxiety disorders. Whereas it also is used to treat these illnesses in children, it is not currently approved by the Food and Drug Administration for use in this population. Sertraline use has been increasing secondary to its efficacy and its more tolerable side effect profile than the tricyclic antidepressants. It is also much safer in overdose than the tricyclic antidepressants. Although there have been numerous reports of sertraline overdose in adults, reports in the pediatric population are much less common. We review the literature regarding sertraline overdose in children, describe a case of sertraline ingestion in a 22-month-old infant, and discuss the treatment of such an overdose.

Tricyclic antidepressant (TCA) ingestions remain a serious and not uncommon overdose in children. In adults, a terminal 40 millisecond QRS vector (T40-ms) between 120 and 270 degrees has been proposed as a marker for TCA overdose; however, the normal rightward deviation and high incidence of incomplete right bundle branch block noted in the electrocardiograms (ECGs) of young children may limit the usefulness of this criterion in this population. A retrospective chart review of pediatric patients less than 11 years of age admitted to the Hospital for Sick Children with birth dates after 1971 identified by International Classification of Diseases, Ninth Edition, coding for TCA ingestion was undertaken, and data related to complications were collected and reviewed. The ECGs of 35 children presenting with TCA ingestion were examined by two blinded cardiologists and the T40-ms as well as QRS, QTc, and PR intervals were calculated and compared to those of 35 healthy age-matched controls undergoing routine ECGs. In the 35 children (aged 48 +/- 39 months [mean +/- SD]) with a history of TCA ingestion, symptoms were categorized as significant in 18 (51%), mild in 12 (34%), and none in five (14%). Seizures were present in 13 (37%), hypotension in three (9%), and arrhythmias in five (14%). The mean T40-ms axes in the TCA and control groups were 111 +/- 66 degrees and 97 +/- 71 degrees, respectively. A T40-ms between 120 and 270 degrees had a sensitivity of 38% and a specificity of 74%. A marked variability in the T40-ms was noted in both the exposed and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The case history described herein illustrates many of the salient clinical and laboratory features of acute salicylate overdose. Aspirin overdose remains a commonly used means of attempting suicide in young adults. This case demonstrates the role of the laboratory in the management of salicylate overdose. Medical treatment of several critical concurrent metabolic responses was dependent on frequent evaluations of serum electrolytes, blood and urine pH, blood PO2, blood PCO2, and blood HCO3- concentrations. In addition, essential to her excellent medical care was the ongoing close interaction between the clinical toxicology laboratory and the clinical staff.

Ethylene glycol has long been recognized as a potentially lethal poison and remains available today as automotive antifreeze and windshield deicer fluids. Ethylene glycol is rapidly absorbed from the gastrointestinal tract, with peak levels measured one to four hours after ingestion. Metabolism of the parent compound and the production of several organic acids are responsible for the metabolic acidosis observed in ethylene glycol poisoning. Target organ cellular damage is seen in the kidney, brain, myocardium, pancreas, and blood vessel walls. Renal tubular deposition of calcium oxalate crystals is felt to be responsible for the development of the severe renal injury which may accompany ethylene glycol ingestion. The clinical course is quite varied and includes inebriation, hematuria, cardiorespiratory compromise, and neurologic effects. Prompt diagnosis and initiation of treatment, including ethanol therapy and hemodialysis, is necessary to ameliorate the effects of ethylene glycol ingestion. Two cases of ethylene glycol poisoning, one accidental and one intentional, are reviewed.