Use of Intravenous Lipid Emulsion Therapy and Insulin in a Case of Tarka Intoxication.

INTRODUCTION: Tarka (trandolapril/verapamil hydrohloride extended-release) is a fixed-dose combination antihypertensive drug formed from verapamil hydrochloride and trandolapril. Toxicologic manifestations of Tarka overdose are altered mental status, bradycardia, hypotension, atrioventricular block (first-degree), hyperglycemia, metabolic acidosis, and shock. CASE PRESENTATION: We report a case of Tarka toxicity in a 2-year-old girl who presented with altered mental status, cardiogenic shock, hypotension, bradycardia, severe metabolic acidosis, hyperglycemia, and first-degree atrioventricular block. We started fluid resuscitation, epinephrine, norepinephrine, and insulin. Because of the patient's hyperlactatemia and hypotension despite standard therapies, we initiated intravenous lipid emulsion (ILE) therapy, after which her condition improved promptly. DISCUSSION: Tarka overdose may be life-threatening as it can cause cardiogenic shock. In our patient, the regression of lactate elevation in a short time with ILE therapy and the improvement of her general condition highlight the importance of ILE. CONCLUSIONS: ILE is an alternative treatment method for acute lipophilic drug intoxications, such as Tarka.

Calcium Channel Blocker Toxicity Causing Acute Respiratory Distress Syndrome: A Commonly Used Drug Triggering a Life-Threatening Condition.

INTRODUCTION: Calcium channel blockers (CCBs) are commonly used but have the potential to cause substantial toxicity. One such underreported toxicity of CCB use is the development of acute respiratory distress syndrome (ARDS). CASE PRESENTATION: 44-year-old previously healthy woman presented to the emergency department (ED) having taken 60 tablets of 125 mg extended-release verapamil and 90 tablets of 0.25 mg clonazepam with the intent to commit suicide. On presentation to the ED, she was sedated and intubated for airway protection. She received aggressive medical resuscitation and was ventilated using low tidal volume mechanical ventilation. The hospital course was complicated by worsening hypoxia and a chest x-ray demonstrating bilateral patchy geographic areas of airspace opacities consistent with ARDS. On day 5 of hospitalization, the patient's clinical status improved significantly, and she was subsequently weaned off vasopressors and extubated. DISCUSSION: CCB toxicity can result in profound hypotension, shock, bradycardia, and conduction blocks, as well as hyperglycemia, acidosis and acute kidney injury, and ARDS. It is important for clinicians to understand the signs and symptoms of CCB toxicity, as well as how to treat it.

Secondary colonic necrosis. Case report.

BACKGROUND: Colonic vascular lesion secondary to verapamil overdose is mediated by free radicals, forming vascular microtrombos and endotoxin generation, being a difficult diagnosis. CLINICAL CASE: A 27-year-old female is admitted with an acute abdomen of 4 days after an event referred for a suicidal attempt due to an overdose of verapamil, operating surgically where there is a right transmural colon necrosis, performing a right hemicolectomy with terminal ileostomy. CONCLUSIONS: Recognize and properly treat an acute abdomen, not always reach an adequate diagnosis, so a thorough history could conclude.

ANTECEDENTES: La lesión vascular colónica secundaria a la sobredosis de verapamilo, es mediada por radicales libres, formando microtrombos vasculares y generación de endotoxinas, siendo un diagnostico difícil. CASO CLÍNICO: Femenino de 27 años, ingresa con abdomen agudo de 4 días posteriores a un evento remitido de intento suicida por sobredosis de verapamilo, interviniéndose quirúrgicamente donde se halla necrosis colónica transmural derecha, realizando hemicolectomía derecha con ileostomía terminal. CONCLUSIONES: Reconocer y tratar de forma adecuada un abdomen agudo, no siempre se suele llegar a un adecuado diagnostico, por lo cual una minuciosa anamnesis lograría concluirlo.

The safety of high-dose insulin euglycaemia therapy in toxin-induced cardiac toxicity.

CONTEXT: High-dose insulin euglycaemia (HIE) is recommended in the management of toxin-induced cardiac toxicity, with increasing insulin doses now being used. We aimed to investigate the safety of HIE in toxin-induced cardiac toxicity. METHODS: This was a retrospective review of cases from two clinical toxicology units. Demographics, toxin(s) ingested, clinical effects, investigations (serum glucose, electrolytes), treatments (insulin, glucose, electrolyte replacement), length of stay (LOS) and outcomes were extracted from the patients' medical records. Associations between insulin and glucose/electrolyte homeostasis were explored by comparing insulin administration and glucose or electrolyte concentrations and replacement. RESULTS: There were 22 patients (12 females), median age 57 years (15-88 years) treated with HIE. There were 12 beta-blocker, six calcium channel blocker and three combined beta-blocker and calcium channel blocker ingestions. A total of 19 patients had a systolic blood pressure <80mmHg and 18 patients required inotropes in addition to HIE. There were three deaths. Despite glucose and electrolyte replacement, 16 patients (73%) developed hypoglycaemia (Reference range [RR] < 3.5 mmol/L or <63 mg/dl). In 7 patients, hypoglycaemia was mild (2.5-3.4 mmol/L or 45-62 mg/dl) and in nine was severe (<2.5 mmol/L or <45 mg/dl). There were no neurological effects from hypoglycaemia. A total of 18 patients (82%) developed hypokalaemia (<3.5 mEq/L). In 16 patients, this was mild (2.5-3.4 mEq/L). There were no cardiac arrhythmias associated with this hypokalaemia. There was no apparent association between insulin dosing and severity of hypoglycaemia or hypokalaemia, or in glucose or potassium replacement. Median insulin loading dose was 80U (range 50-125 U) and the median maximum insulin infusion rate was 150 U/h (range 38-1500 U/h). Median glucose infusions rates were 37.5g/h (range 4-75g/h). There was no apparent association between insulin and glucose administration. Glucose was administered for a median of 18h after ceasing insulin. The duration of glucose administration after ceasing insulin increased with the rate and total insulin administered during HIE. DISCUSSION: Despite the benefits of HIE in toxin-induced cardiac toxicity, it caused significant disruption to glucose and electrolyte homeostasis, although there were no apparent complications from this. There was no association by comparing the amount of insulin administered on adverse effects or glucose administered, suggesting higher doses of insulin are associated with no more adverse effects.

A Report of Brugada Syndrome Presenting with Cardiac Arrest Triggered by Verapamil Intoxication.

BACKGROUND: Brugada syndrome is a disease characterized by a specific electrocardiographic pattern and an increased risk of sudden cardiac death. We present this case with the updated literature to emphasise the need to consider the diagnosis of Brugada syndrome in patients admitted to the emergency ward with sudden cardiac arrest. CASE REPORT: A 16-year-old female patient was admitted to the emergency ward with complaints of weakness and abdominal pain, and she had four cardiac arrests during her evaluation period. She was referred to our clinic for permanent pacemaker implantation. She was on a temporary pace maker after having had C-reactive protein. Her physical exam was normal except for bilaterally decreased lung sounds. Lung x-ray and computed tomography, which were performed by another institution, revealed minimal pleural effusion and nothing else of significance. Blood and peritoneal fluid samples were sterile. Echocardiographic exam and cardiac enzymes were also in the normal ranges. Electrocardiographic showed incomplete right branch block in leads V1 and V2. An ajmaline test revealed specific electrocardiographic findings of the type I Brugada pattern. We proposed implanting an implantable cardioverter defibrillator to the patient as there were positive findings on the ajmaline test as well as a history of sudden cardiac arrest. After this treatment proposal, the patient's family admitted that she had taken a high dose of verapamil and thus, the encountered bradycardia was associated with verapamil overuse. The ajmaline test was repeated as it was contemplated that the previous positive ajmaline test had been associated with verapamil overuse. Implantable cardioverter defibrillator implantation was proposed again as there was a history of sudden cardiac arrest; however, the family did not consent to implantable cardioverter defibrillator, and the patient was discharged and followed up. CONCLUSION: Brugada syndrome should be considered for patients who are admitted to the emergency ward with sudden cardiac arrest though surface electrocardiographic is normal. If there is a suspicion of Brugada syndrome, repeated electrocardiographic should be performed on different occasions. Diagnosis can be clarified by upper costal electrocardiographic or by administering Na channel blockers during electrocardiographic performance.

Severe verapamil intoxication despite correct use of low-dose verapamil.

We report a case of an adult patient using chronic low-dose verapamil who developed severe verapamil intoxication. A 57-year-old male patient was presented at the emergency room after a collapse of unknown etiology. The airway was compromised, and thus, an endotracheal tube was inserted. The patient deteriorated hemodynamically. Because of verapamil use and bradycardia, verapamil intoxication was suspected. The treatment was supported with intravenous fluids, calcium, inotropes, and a transvenous pacemaker. The patient progressively developed circulatory shock. Verapamil intoxication was confirmed, and therapy was adjusted accordingly. Insulin and calcium infusion were intensified, and glucagon and Intralipid® infusion were initiated. With this therapy, the patient's condition improved rapidly. We found different factors in this patient that could have precipitated this event such as diminished metabolism by cytochrome P450 iso-enzymes, a slightly diminished renal function with hypoalbuminemia, and interaction with other protein-binding drugs.

In Vitro Studies Indicate Intravenous Lipid Emulsion Acts as Lipid Sink in Verapamil Poisoning.

Intravenous lipid emulsion (ILE), a component of parenteral nutrition, consists of a fat emulsion of soy bean oil, egg phospholipids, and glycerin. Case reports suggest that ILE may reverse hypotension caused by acute poisoning with lipophilic drugs such as verapamil, but the mechanism remains unclear. The methods used are the following: (1) measurement of ILE concentration in serum samples from a patient with verapamil poisoning treated with ILE, (2) measurement of free verapamil concentrations in human serum mixed in vitro with increasing concentrations of ILE, and (3) measurement of murine ventricular cardiomyocyte L-type Ca(2+) currents, intracellular Ca(2+), and contractility in response to verapamil and/or ILE. Maximum patient serum ILE concentration after infusion of 1 L ILE over 1 h was approximately 1.6 vol%. In vitro GC/MS verapamil assays showed that addition of ILE (0.03-5.0 vol%) dose-dependently decreased the free verapamil concentration in human serum. In voltage-clamped myocytes, adding ILE to Tyrode's solution containing 5 µM verapamil recovered L-type Ca(2+) currents (ICa). Recovery was concentration dependent, with significant ICa recovery at ILE concentrations as low as 0.03 vol%. ILE had no effect on ICa in the absence of verapamil. In field-stimulated intact ventricular myocytes exposed to verapamil, adding ILE (0.5 %) resulted in a rapid and nearly complete recovery of myocyte contractility and intracellular Ca(2+). Our in vitro studies indicate that ILE acts as a lipid sink that rapidly reverses impaired cardiomyocyte contractility in the continued presence of verapamil.

Multi-drug intoxication fatality involving atorvastatin: A case report.

Mixed antihypertensive drug intoxication poses a significant risk for patient mortality. In tandem to antihypertensives, hypolipidemic medicines (especially statins) are often prescribed. Among their well-known adverse effects belongs rhabdomyolysis. We report a case of fatal multi-drug overdose in a 65-year-old female alcoholic. The patient was unconscious at admission. Empty blister packs indicated the abuse of 250 tablets of urapidil, 42 tablets of verapamil/trandolapril, 50 tablets of moxonidin, 80 tablets of atorvastatin and 80 tablets of diacerein. Standard measures (gastric lavage, activated charcoal, mechanical ventilation, massive doses of vasopressors, volume expansion, diuretics and alkalinization) failed to provide sufficient drug elimination and hemodynamic support and the sufferer deceased on the fourth day. Dramatic elevations of serum myoglobin (34,020 µg/L) and creatine kinase (219 µkat/L) were accompanied by rise in cardiac troponin I and creatinine. Gas chromatography revealed ethanol 1.17 g/kg (blood) and 2.81 g/kg (urine). Thin layer chromatography and gas chromatography of gastric content and urine verified verapamil, moxonidin and urapidil fragment (diacerein method was unavailable). Atorvastatin and trandolapril concentrations (LC-MS(n)) equaled 277.7 µg/L and 57.5 µg/L, resp. (serum) and 8.15 µg/L and 602.3 µg/L, resp. (urine). Histology confirmed precipitates of myoglobin with acute necrosis of proximal renal tubules in association with striated muscle rhabdomyolysis and myocardial dystrophy. Cardiogenic-distributive shock in conjunction with acute renal failure due to the combined self-poisoning with vasoactive agents and atorvastatin were determined to be this decedent's immediate cause of death. The manner of death was assigned to be suicidal.

Lipid emulsion therapy given intraosseously in massive verapamil overdose.

Intravenous fat emulsion (IFE) therapy has been widely used in the emergency department (ED) for treating various medication overdoses. The standard recommended route to administer IFE therapy is intravenously through a peripheral or central vein. No reports of intraosseous (IO) administration in humans could be found in the literature after a brief search. We report of a patient emergently receiving IFE through the IO route. A 24-year-old woman presented to ED after a massive deliberate verapamil overdose. A decision was then made to start both vasopressors and 20% IFE therapy. Central access was established, and a norepinephrine drip was started. Intravenous fat emulsion was to be started, but peripheral access was lost at that time and not able to be reestablished. An IO line was then placed without difficulty in the left proximal tibia using an EZ-IO system. Approximately half way during the bolus administration, the intravenous pump began to alarm that the infusion was not flowing adequately. At this point, peripheral access was obtained, and IFE infusion was moved to that site. We believe that this is the first report of IFE administered via the IO route in a human. This case report illustrates a novel way of administering IFE therapy in an emergency situation where intravenous access may be difficult to obtain.

Intravenous lipid emulsion in the emergency department: a systematic review of recent literature.

BACKGROUND: Intravenous lipid emulsion (ILE) has been broadly attempted in the resuscitation of neurologic and cardiac toxic drug overdoses, however, the role of ILE in the emergency department is poorly defined. OBJECTIVE: This review aims to identify recent literature on the use of ILE in humans as an antidote and to familiarize emergency providers with the indications, availability, dosing recommendations, and adverse reactions associated with ILE use. METHODS: A systemic literature search of MEDLINE, EMBASE, and major toxicology conference abstracts was performed for human cases using ILE as an antidote with documented clinical outcomes through January 2014. RESULTS: Ninety-four published articles and 40 conference abstracts were identified, 85% of which had positive outcomes. The most common indication for ILE was for local anesthetic systemic toxicity (LAST). The most common nonlocal anesthetic xenobiotics were tricyclic-antidepressants and verapamil. DISCUSSION: No standard of care is defined for the use of ILE, although the American Heart Association recommends use in LAST, and the American College of Medical Toxicology recommends consideration for circumstances of hemodynamic instability resultant from lipid-soluble xenobiotics. ILE should be administered per American Society of Regional Anesthesia and Pain Medicine dosing recommendations. Laboratory interference, pancreatitis, respiratory distress syndrome, and interference with vasopressors should be considered as risks but are uncommon. CONCLUSIONS: In the setting of severe hemodynamic compromise by lipid-soluble xenobiotics, ILE may be considered for resuscitation by emergency physicians. As such, ILE may be stocked in emergency departments in close proximity to resuscitation rooms and areas where local nerve blocks are performed.

[Verapamil intoxication: beware of the delayed effect]. / Intoxication aigüe au vérapamil : attention à l'effet retard.

Intoxication with calcium channel inhibitory drugs is rare but mortality rates reach 10 %. We report the case of a 5-year-old girl who had ingested five 240-mg tablets of extended-release verapamil (VLP) and a tablet of bromazepam. Thirty hours after the ingestion she had a vasoplegic shock, heart conduction disorders, and metabolic complications. She was treated in pediatric intensive care with continuous epinephrine and insulin and recovered completely 60h after the ingestion. This case underlines the danger of calcium channel blocker overdose, increased by the extended-release mechanism: the drug effect is to slow down gastric motility - which explains the latency of the symptoms - but this also increases the drug absorption, inducing a vicious circle. These mechanisms in calcium blocker intoxication need to be kept in mind in order to decrease the mortality of such accidents.

Papel del propofol en la intoxicación por verapamilo / Role of propofol in verapamil intoxication

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Acute respiratory distress syndrome after verapamil intoxication: case report and literature review.

Verapamil intoxication is a life-threatening condition that often presents with severe hemodynamic instability and requires vasopressor support. There are also documented case reports of the development of non-cardiogenic pulmonary oedema after verapamil overdose. However, the exact mechanisms responsible for pulmonary oedema remain unclear. Here, we describe a 36-year-old woman who was admitted to the intensive care unit after ingesting high-dose verapamil and subsequently developed acute respiratory distress syndrome soon after hemodynamic stabilization. Possible mechanisms are presented after taking into account findings in the current literature. Acute respiratory distress syndrome should be considered early during the evaluation of patients with verapamil intoxication.