Refractory Shock from Amlodipine Overdose Overcomed with Hyperinsulinemia.

Intoxication from calcium channel blockers exhibits almost 50% mortality rates. Amlodipine is a long-acting dihydropyridine and inappropriate dosage poses a great threat for profound vasodilation, hypotension, and refractory vasopressor-resistant shock. A 72-year-old woman with unremarkable medical history presented to the emergency department due to amlodipine overdose after a suicide attempt attributed to COVID-19 pandemic severe anxiety disorder. Vital signs at presentation: heart rate 82 beats/ min, arterial pressure 72/55 mmHg, and oxygen saturation 98%. Resuscitation was initiated with intravenous infusion of normal saline 0,9%, noradrenaline, and calcium chloride, while activated charcoal was orally administrated; however, blood pressure remained at 70/45 mmHg. Abruptly, she experienced acute pulmonary edema and was finally intubated. We commenced high-dose insulin infusion with Dextrose 10% infusion to maintain euglycemic hyperinsulinemia. Hemodynamic improvement occurred after 30 min, systolic blood pressure raised to 95 mmHg, and decongestion was achieved with intravenous furosemide. Insulin effect was dose-dependent and patient's hemodynamic status improved after insulin uptitration. Eight days later, the patient was weaned from the mechanical ventilation and she was successfully discharged after 14 days. High-dose intravenous infusion of insulin up to 10 units/kg per hour appears as an inotropic agent possibly through alterations in myocardial metabolism of fatty acids and augmentation of insulin secretion and uptake. This regimen possibly exhibits additional vasotropic properties. We conclude that euglycemic hyperinsulinemia is a potentially advantageous treatment in CCB toxicity.

First-Line Vasopressor and Mortality Rates in ED Patients with Acute Drug Overdose.

INTRODUCTION: While emergency department (ED) visits for acute drug overdose are at an all-time high, the importance of vasopressors to treat circulatory shock in this patient population remains unclear. This study investigated the association between first-line vasopressor and mortality, for both push-dose and infusion, in this patient population. METHODS: From a prospective cohort of consecutive ED patients with drug overdose at two urban teaching centers over 5 years, we performed a secondary data analysis of patients with circulatory shock, defined as hypotension requiring either vasopressors, high-dose insulin euglycemia therapy, or both. The first-line vasopressor (push-dose and infusion) was analyzed for associations with the primary outcome (in-hospital mortality) and secondary outcomes (24-hour mortality, ICU LOS). Subgroup analysis of beta-/calcium-channel blocker overdose was performed to evaluate impact of antidotal therapies. Data analysis included multivariable regression. RESULTS: Fifty-five patients with circulatory shock were analyzed, in whom there was 20% 24-hour mortality, 42% in-hospital mortality, 730-minute mean vasopressor duration, and 53.4-hour median ICU LOS. On multivariable analysis, there was significantly decreased adjusted odds of in-hospital mortality with first-line push-dose phenylephrine (aOR 0.06, CI 0.01-0.55), and significantly increased adjusted odds of in-hospital mortality with first-line push-dose epinephrine (aOR 60.8, CI 6.1-608). Of the first-line infusions, norepinephrine had the lowest odds of in-hospital mortality (aOR 0.80, CI 0.2-3.1). CONCLUSIONS: In ED patients with undifferentiated drug overdose and circulatory shock, the first-line vasopressor is associated with in-hospital mortality. First-line push-dose phenylephrine was associated with the lowest odds of in-hospital mortality. Future randomized studies are warranted for validation.

How Much Vitamin D is Too Much? A Case Report and Review of the Literature.

BACKGROUND: The beneficial effects of vitamin D, together with the high prevalence of vitamin D deficiency, have led to an expanding use of vitamin D analogues. While inappropriate consumption is a recognized cause of harm, the determination of doses at which vitamin D becomes toxic remains elusive. CASE PRESENTATION: A 56-year woman was admitted to our Hospital following a 3-week history of nausea, vomiting, and muscle weakness. The patient had been assuming a very high dose of cholecalciferol for 20 months (cumulative 78,000,000UI, mean daily 130,000UI), as indicated by a non-- conventional protocol for multiple sclerosis. Before starting vitamin D integration, serum calcium and phosphorus levels were normal, while 25OH-vitamin D levels were very low (12.25 nmol/L). On admission, hypercalcemia (3.23 mmol/L) and acute kidney injury (eGFR 20 mL/min) were detected, associated with high concentrations of 25OH-vitamin D (920 nmol/L), confirming the suspicion of vitamin D intoxication. Vitamin D integration was stopped, and in a week, hypercalcemia normalized. It took about 6 months for renal function and 18 months for vitamin D values to go back to normal. CONCLUSION: This case confirms that vitamin D intoxication is possible, albeit with a high dose. The doses used in clinical practice are far lower than these and, therefore, intoxication rarely occurs even in those individuals whose baseline vitamin D serum levels have never been assessed. Repeated measurements of vitamin D are not necessary for patients under standard integrative therapy. However, patients and clinicians should be aware of the potential dangers of vitamin D overdose.

Calcium channel blocker and beta blocker overdose, and digoxin toxicity management.

While relatively uncommon, an overdose of calcium channel blockers, beta blockers, or digoxin can result in significant morbidity and mortality, and management can be complex. An acute overdose will require different management strategies than chronic toxicity while on therapeutic dosing. Toxicity from these agents must be considered in bradycardic and hypotensive patients. This supplement provides an evidence-based overview of emergency department management of calcium channel blocker overdose, beta blocker overdose, and digoxin toxicity, and focuses on the caveats of treatment for each.

[Peripheral neuropathy with hypervitaminosis B6 caused by self-medication]. / Neuropathie périphérique avec hypervitaminose B6 provoquée par l'automédication.

INTRODUCTION: Vitamin B6 is contained in a number of over-the-counter drugs and vitamin supplements. It may cause severe neurological troubles in case of overdosage. CASE REPORT: We report the case of a 92-year-old women with gait disorders. A diagnosis of peripheral neuropathy with both motor and sensitive deficits was established and investigated. Blood level of vitamin B6 was measured to investigate a potential deficiency. Unexpectedly, the results showed hypervitaminosis B6, which appears to be due to self-administration of an over-the-counter drug containing vitamin B6. Discontinuation of this drug was associated with decrease in vitamin B6 level as well as gait improvement. We also discuss the toxicity of vitamin B6. CONCLUSION: Hypervitaminosis B6 remains a possible cause of peripheral neuropathy and it may be caused by self-administration of over-the-counter vitamin-containing drugs.

Using the 150 rule to prevent hepatotoxicity from acetaminophen.

Acetaminophen-induced hepatotoxicity is the most common cause of acute liver failure in adults and a major cause of acute liver failure in children. Prompt treatment with N-acetylcysteine can mitigate hepatotoxicity and progression to liver failure. This article describes a 16-year-old girl who ingested a large dose of extra-strength acetaminophen, and how the 150 rule was used in her management.

Polymerase-free measurement of microRNA-122 with single base specificity using single molecule arrays: Detection of drug-induced liver injury.

We have developed a single probe method for detecting microRNA from human serum using single molecule arrays, with sequence specificity down to a single base, and without the use of amplification by polymerases. An abasic peptide nucleic acid (PNA) probe-containing a reactive amine instead of a nucleotide at a specific position in the sequence-for detecting a microRNA was conjugated to superparamagnetic beads. These beads were incubated with a sample containing microRNA, a biotinylated reactive nucleobase-containing an aldehyde group-that was complementary to the missing base in the probe sequence, and a reducing agent. When a target molecule with an exact match in sequence hybridized to the capture probe, the reactive nucleobase was covalently attached to the backbone of the probe by a dynamic covalent chemical reaction. Single molecules of the biotin-labeled probe were then labeled with streptavidin-ß-galactosidase (SßG), the beads were resuspended in a fluorogenic enzyme substrate, loaded into an array of femtoliter wells, and sealed with oil. The array was imaged fluorescently to determine which beads were associated with single enzymes, and the average number of enzymes per bead was determined. The assay had a limit of detection of 500 fM, approximately 500 times more sensitive than a corresponding analog bead-based assay, with target specificity down to a single base mis-match. This assay was used to measure microRNA-122 (miR-122)-an established biomarker of liver toxicity-extracted from the serum of patients who had acute liver injury due to acetaminophen, and control healthy patients. All patients with liver injury had higher levels of miR-122 in their serum compared to controls, and the concentrations measured correlated well with those determined using RT-qPCR. This approach allows rapid quantification of circulating microRNA with single-based specificity and a limit of quantification suitable for clinical use.

Sedative-Hypnotic Drug Withdrawal Syndrome: Recognition And Treatment.

Sedative-hypnotic drugs include gamma-Aminobutyric acid (GABA)ergic agents such as benzodiazepines, barbiturates, gamma-Hydroxybutyric acid [GHB], gamma-Butyrolactone [GBL], baclofen, and ethanol. Chronic use of these substances can cause tolerance, and abrupt cessation or a reduction in the quantity of the drug can precipitate a life-threatening withdrawal syndrome. Benzodiazepines, phenobarbital, propofol, and other GABA agonists or analogues can effectively control symptoms of withdrawal from GABAergic agents. Managing withdrawal symptoms requires a patient-specific approach that takes into account the physiologic pathways of the particular drugs used as well as the patient's age and comorbidities. Adjunctive therapies include alpha agonists, beta blockers, anticonvulsants, and antipsychotics. Newer pharmacological therapies offer promise in managing withdrawal symptoms.

Dofetilide in Overdose: A Case Series from Poison Center Data.

Dofetilide is a class III antiarrhythmic used for treating atrial dysrhythmias. Though its adverse effects are well described in routine use, very little is known about dofetilide toxicity in overdose. This is a retrospective case series of consecutive patients reported to our poison center after dofetilide overdose. Twenty-seven cases were included. Seventeen patients were treated at a healthcare facility, and of these, eight were admitted. Twenty-one patients took one extra capsule, four took someone else's medication, one took three extra capsules, and one had a large intentional overdose. Ten patients had co-ingestants reported, including three QT-prolonging agents. No one required cardioversion, defibrillation, CPR, or overdrive pacing. The patient who reported taking 90 times his usual dose in suicide attempt was the only patient to have significant clinical effects. He experienced an 8-beat run of non-sustained ventricular tachycardia, frequent multifocal PVCs, and ventricular bigeminy. He received magnesium sulfate and potassium chloride supplementation. In this series, unintentional small overdoses did not result in significant clinical effects and were often managed successfully at home, despite the fact that information showing a single capsule can cause torsades. This study is limited by its small sample size, retrospective design, and reliance on incomplete information.

Conventional and Unconventional Lifesaving Therapies in an Adolescent With Amlodipine Ingestion.

Amlodipine, a dihydropyridine calcium channel blocker, is commonly prescribed for the treatment of hypertension. Ingestion of an overdose leads to severe hypotension; if the hypotension is not treated, death may be imminent. Conventional and unconventional interventions were used to treat an adolescent who ingested a life-threatening dose of amlodipine. Severe hypotension resistant to conventional treatment with intralipids and hyperinsulinemia-euglycemia therapy led to the use of plasmapheresis and a pneumatic antishock garment as lifesaving measures. Plasmapheresis has been described in only one other case of severe amlodipine overdose, and the use of a pneumatic antishock garment has never been described in the management of a calcium channel blocker overdose. Because short-term use of a pneumatic antishock garment has associated risks, the critical care nurse's anticipation of side effects and promotion of safe use of the garment were instrumental in the patient's care and outcome. (Critical Care Nurse 2016; 36[4]:64-69).

Protocol: changes in rates of opioid overdose and poisoning events in an integrated health system following the introduction of a formulation of OxyContin® with abuse-deterrent properties.

BACKGROUND: Addiction, overdoses and deaths resulting from prescription opioids have increased dramatically over the last decade. In response, several manufacturers have developed formulations of opioids with abuse-deterrent properties. For many of these products, the Food and Drug Administration (FDA) recognized the formulation with labeling claims and mandated post-marketing studies to assess the abuse-deterrent effects. In response, we assess differences in rates of opioid-related overdoses and poisonings prior to and following the introduction of a formulation of OxyContin® with abuse-deterrent properties. METHODS/DESIGN: To assess effects of this formulation, electronic medical record (EMR) data from Kaiser Permanente Northwest (KPNW) and Kaiser Permanente Northern California (KPNC) are linked to state death data and compared to chart audits. Overdose and poisoning events will be categorized by intentionality and number of agents involved, including illicit drugs and alcohol. Using 6-month intervals over a 10-year period, trends will be compared in rates of opioid-related overdoses and poisoning events associated with OxyContin® to rates of events associated with other oxycodone and opioid formulations. Qualitative interviews with patients and relatives of deceased patients will be conducted to capture circumstances surrounding events. DISCUSSION: This study assesses and tracks changes in opioid-related overdoses and poisoning events prior to and following the introduction of OxyContin® with abuse-deterrent properties. Public health significance is high because these medications are designed to reduce abuse-related behaviors that lead to important adverse outcomes, including overdoses and deaths.

A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment.

CONTEXT: Synthetic cannabinoids (SCs) such as "Spice", "K2", etc. are widely available via the internet despite increasing legal restrictions. Currently, the prevalence of use is typically low in the general community (<1%) although it is higher among students and some niche groups subject to drug testing. Early evidence suggests that adverse outcomes associated with the use of SCs may be more prevalent and severe than those arising from cannabis consumption. OBJECTIVES: To identify systematically the scientific reports of adverse events associated with the consumption of SCs in the medical literature and poison centre data. METHOD: We searched online databases (Medline, PsycInfo, Embase, Google Scholar and Pubmed) and manually searched reference lists up to December 2014. To be eligible for inclusion, data had to be from hospital, emergency department, drug rehabilitation services or poison centre records of adverse events involving SCs and included both self-reported and/or analytically confirmed consumption. RESULTS: From 256 reports, we identified 106 eligible studies including 37 conference abstracts on about 4000 cases involving at least 26 deaths. Major complications include cardiovascular events (myocardial infarction, ischemic stroke and emboli), acute kidney injury (AKI), generalized tonic-clonic seizures, psychiatric presentations (including first episode psychosis, paranoia, self-harm/suicide ideation) and hyperemesis. However, most presentations were not serious, typically involved young males with tachycardia (≈ 37-77%), agitation (≈ 16-41%) and nausea (≈ 13-94%) requiring only symptomatic care with a length of stay of less than 8 hours. CONCLUSIONS: SCs most frequently result in tachycardia, agitation and nausea. These symptoms typically resolve with symptomatic care, including intravenous fluids, benzodiazepines and anti-emetics, and may not require inpatient care. Severe adverse events (stroke, seizure, myocardial infarction, rhabdomyolysis, AKI, psychosis and hyperemesis) and associated deaths manifest less commonly. Precise estimates of their incidence are difficult to calculate due to the lack of widely available, rapid laboratory confirmation, the variety of SC compounds and the unknown number of exposed individuals. Long-term consequences of SCs use are currently unknown.

Vitamin D toxicity resulting from overzealous correction of vitamin D deficiency.

BACKGROUND: Vitamin D toxicity, often considered rare, can be life-threatening and associated with substantial morbidity, if not identified promptly. OBJECTIVE: To describe clinical and biochemical features, risk factors and management of patients with vitamin D toxicity seen between January 2011 and January 2013. METHODOLOGY: Patients presenting with vitamin D toxicity, between January 2011 and January 2013, at single tertiary care centre in Delhi-NCR, India, were included. Evaluation included detailed clinical history and biochemical tests including serum calcium, phosphorus, creatinine, intact parathyroid hormone and 25-hydroxyvitamin D (25(OH)D). RESULTS: Sixteen patients with vitamin D toxicity could be identified. Clinical manifestations included nausea, vomiting, altered sensorium, constipation, pancreatitis, acute kidney injury and weight loss. Median (range) age was 64·5 (42-86) years. Median (range) serum 25(OH)D level and median (range) serum total serum calcium level were 371 (175-1161) ng/ml and 13·0 (11·1-15·7) mg/dl, respectively. Overdose of vitamin D caused by prescription of mega-doses of vitamin D was the cause of vitamin D toxicity in all cases. Median (range) cumulative vitamin D dose was 3,600,000 (2,220,000-6,360,000) IU. CONCLUSION: Our data demonstrate an emergence of vitamin D toxicity as an increasingly common cause of symptomatic hypercalcaemia. Irrational use of vitamin D in mega-doses resulted in vitamin D toxicity in all cases. Awareness among healthcare providers regarding the toxic potential of high doses of vitamin D and cautious use of vitamin D supplements is the key to prevent this condition.

Continuous venovenous hemodiafiltration along with charcoal hemoperfusion for the management of life-threatening lercanidipine and amlodipine overdose.

Overdose with calcium channel blockers is uncommon, but is associated with high mortality. The management includes fluid resuscitation, calcium gluconate, glucagon, vasopressors, and high-dose insulin-euglycemia therapy. We describe a rare case of massive overdose of lercanidipine with shock, refractory to conventional therapies and multi-organ failure. Charcoal hemoperfusion with continuous venovenous hemodiafiltration was then used successfully and the patient showed remarkable recovery.

Intralipid emulsion treatment as an antidote in lipophilic drug intoxications.

Intravenous lipid emulsion (ILE) is a lifesaving treatment of lipophilic drug intoxications. Not only does ILE have demonstrable efficacy as an antidote to local anesthetic toxicity, it is also effective in lipophilic drug intoxications. Our case series involved 10 patients with ingestion of different types of lipophilic drugs. Intravenous lipid emulsion treatment improved Glasgow Coma Scale or blood pressure and pulse rate or both according to the drug type. Complications were observed in 2 patients (minimal change pancreatitis and probable ILE treatment-related fat infiltration in lungs). In our case series, ILE was used for different lipophilic drug intoxications to improve cardiovascular and neurologic symptoms. According to the results, it was found that ILE treatment is a lifesaving agent in lipophilic drug intoxications and it can be used in unconscious patients who have cardiac and/or neurologic symptoms but no history of a specific drug ingestion.

Fatal non-accidental alpha-lipoic acid intoxication in an adolescent girl.

The aim of our report is to increase awareness that the antioxidant alpha-lipoic acid, which is marketed primarily as weight loss and energy supplement, has potentially lethal effects. A 14-year-old girl ingested in suicidal intention a large amount of alpha-lipoic acid, which led to multiorgan failure and subsequent death within 24 h. Multiorgan failure consisted of decreased myocardial contractility, seizures, anuria, thrombocytopenia, and coagulopathy. Therapy consisted of ventilation, anticonvulsive treatment and circulatory support with high-dose catecholamines. According to alpha-lipoic acid serum levels following ingestion the girl must have ingested a minimum of 10 alpha-lipoic acid tablets of 600 mg each. This is the first report on a fatal case of alpha-lipoic acid ingestion, which is intended to inform physicians, pharmacists and patients about critical side effects of this allegedly innocuous drug.

[Acute intoxication in adults - what you should know]. / Akute Intoxikationen bei Erwachsenen - was Sie wissen sollten.

Ingestion of household products and plants are the leading cause for calls to the poison control centres as far as children are involved. Severe intoxication in children has become infrequent due to childproofed package and blister packs for drugs. Chemical accidents in adults give rise to hospital admission in only 5 %. Suicidal selfpoisonings are still a challenge for paramedics, emergency and hospital doctors. Natural toxins as amatoxins, cholchicine and snakebites can lead to severe intoxication. Sedatives, antidepressants and analgesics are the drugs which are often used for suicidal intent due to their availability. Quetiapine and paracetamol are the drugs which are ingested for attempted suicide/ suicide mostly. The treatment of poisoning centers on the severity which can be judged by the poison severity score, the Reed classification or the GCS.Most intoxicated patients can be treated symptomatically or by intensive care measurements. Antidotal treatment however is needed for some specific poisonings.Exact sample drawing is essential for diagnostic and forensic purposes. There is no evidence based proof for the effectiveness of primary detoxification from the gastrointestinal tract like forced emesis, gastric lavage or the use of cathartics. Early after the ingestion of a harmful substance the administration of activated charcoal seems advisable. Hemodialysis can remove water soluble substances with a small volume of distribution. Multiple charcoal administration may exhibit some influence on secondary detoxification. Provision of evidence of the efficacy for newer antidotes like hydroxocobalamin in smoke inhalation, fomepizol for toxic alcohols and silibinin for amanita poisoning are emerging. Two recently recommended therapeutic principles have still to demonstrate their ability: Firstly the treatment of patients with calcium receptor antagonistic and beta-receptor antagonistic agents poisoning by high dose of insulin plus glucose, secondly the treatment for severe intoxication with cardiotoxic and psychotropic drugs with a lipid emulsion (Lipid rescue).It is essential for all doctors to contact a poison control center whenever they are confronted with an intoxicated patient. There they can get advice about which dose is toxic and about the newest therapeutic procedure.

Red clover causing symptoms suggestive of methotrexate toxicity in a patient on high-dose methotrexate.

The case report discusses a very serious interaction between red clover and methotrexate not previously documented. It highlights the potential pitfalls of concomitant use of herbal remedies and conventionally prescribed drugs and the importance of advising our patients about OTC drugs. A 52-year-old woman attended her general practitioner for advice on menopausal flushing. She was on methotrexate weekly injections for severe psoriasis and was not keen to consider anything that would possibly affect her skin. Alternative therapies were discussed and red clover was suggested. This was bought OTC. After the third day of taking red clover capsules (430 mg), the patient developed severe vomiting and epigastric pain. She contacted the dermatology clinic that administers the methotrexate injection and was thought to have symptoms suggestive of methotrexate toxicity even though her liver function tests remained within normal levels. She had been receiving methotrexate injections for nearly two years with no adverse effects. The only new drug that had been started was red clover and this was thought to be the probable cause of the toxicity. It was withdrawn. The patient made a full recovery and received her next injection of methotrexate with no adverse effects. The interaction was reported to the MHRA with a yellow card.