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.

Success in early treatment with lipid emulsion for antihypertension drug overdose patient.

Intravenous lipid emulsion (ILE) is typically applied as a rescue therapy after the use of conventional treatments for beta blocker (BBs) or calcium channel blocker (CCB) overdoses. We describe the case of a 72-year-old man who presented to our ED after attempting suicide by antihypertensive drug overdose. His blood pressure dropped upon arrival at the ED, and we consequently administered multitherapy including relatively early ILE to prevent prolonged hypotension. He regained stable hemodynamic status on the third day and was later discharged without major sequelae.

Successful Treatment of Antihypertensive Overdose Using Intravenous Angiotensin II.

BACKGROUND: Despite multiple treatment options, antihypertensive overdose remains a cause of significant morbidity and mortality. Intravenous angiotensin II (AG II) is approved for use in vasodilatory shock. We describe 2 cases of refractory shock from antihypertensive overdose that were successfully treated using AG II. CASE REPORTS: A 24-year-old female presented after an overdose of multiple antihypertensive medications, including an angiotensin converting enzyme inhibitor (ACEI). She developed hypotension that was refractory to norepinephrine, epinephrine, and vasopressin, with a mean arterial pressure (MAP) of 57 mm Hg 9 h after emergency department arrival. Fifteen minutes after starting AG II at 10 ng/kg/min, her heart rate and MAP rose by 7 beats/min and 12 mm Hg, respectively. Her hemodynamic parameters continued to improve thereafter. She developed acute kidney injury, which resolved prior to discharge. The second patient, a 65-year-old male, presented after an overdose of multiple antihypertensive medications, including an ACEI. Despite norepinephrine, epinephrine, and hyperinsulinemia-euglycemia, he remained bradycardic and hypotensive, with a heart rate of 47 beats/min and MAP of 59 mm Hg. Thirty minutes after starting AG II at 10 ng/kg/min, his heart rate was 61 beats/min and MAP was 66 mm Hg. He recovered without apparent sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Antihypertensive overdose can lead to shock refractory to catecholamine and vasopressin therapy. Our experience suggests that AG II is efficacious in antihypertensive overdose and may be particularly efficacious in instances of ACEI overdose. However, further study is required to confirm the appropriate indication(s).

Electrocardiographic Changes Following Acute Hydralazine Overdose.

Hydralazine is an FDA-approved antihypertensive agent which has been utilized for years either alone or in combination with other medications especially the beta-blockers. Hydralazine works as a direct-acting vasodilator, thereby exerting a decrease in vascular resistance and increase in intravascular volume. When overdosed, hydralazine applies its toxic effects by extending its pharmacological action, which produces hypotension, syncope, tachycardia, and nausea. However, studies and case reports of acute hydralazine toxicity and its effects on electrocardiographic changes are rare, and most of the medical literature have only highlighted its immunological side effects. In this report, we are presenting a case of acute hydralazine overdose in a young woman who ended up in CCU due to remarkably abnormal electrocardiogram and unstable hemodynamics followed by myocardial infarction.

Refractory Hypotension Caused by Prazosin Overdose Combined With Acetaminophen and Naproxen Toxicity: A Case Report and Review of the Literature.

BACKGROUND: Pediatric exposure to prazosin is unusual because it is most commonly indicated for the treatment of hypertension. Prazosin's increase in popularity as a treatment for posttraumatic stress disorder makes it important for emergency physicians to be aware of how to manage potential toxic ingestion because of prazosin overdose. CASE REPORT: A 16-year-old, 76-kg female presented after ingesting 110 mg of prazosin, 209.3 g of acetaminophen, and 55 g of naproxen. She was admitted to the pediatric intensive care unit for rapidly deteriorating hypotension (lowest blood pressure 47/19 mm Hg) refractory to aggressive fluid resuscitation and infusions of epinephrine and norepinephrine each at 0.5 mcg/kg/min. Stabilization of blood pressure was eventually achieved, and associated with use of a vasopressin infusion of 0.004 units/kg/min. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Because of the increasing exposure of children to prazosin, clinicians should be aware of the pharmacology behind alpha-1 antagonist overdose and consider treatment options, such as vasopressin, when hypotension is resistant to standard fluid and catecholamine therapy.

Pediatric Minoxidil Exposures Reported to Texas Poison Centers.

OBJECTIVES: It has been suggested that ingestion of even small amounts of minoxidil by young children may result in serious adverse effects. The intent of this study was to describe pediatric minoxidil exposures reported to a statewide poison center system. METHODS: Cases were minoxidil exposures among patients 5 years or younger reported to Texas poison centers during 2000 to 2014. The distribution by various demographic and clinical factors was determined. RESULTS: Of 125 total cases, 58% were male and 78% aged 1 to 2 years. Ingestion alone was reported in 92% of the exposures. Ninety-eight percent of the exposures were unintentional, and 94% occurred at the patient's own residence. Sixty-two percent of the patients were managed on site. The outcome was not serious (no effect, minor effect, not followed [nontoxic], not followed [minimal effects]) in 88% of the exposures. The most common adverse effect was vomiting, reported in 8% of the exposures. The most common treatments were dilution/irrigation/wash (53%), activated charcoal (18%), food/snack (17%), and intravenous fluids (8%). CONCLUSIONS: Few pediatric minoxidil exposures were reported to Texas poison centers. Of these exposures, most involved ingestion, were unintentional, and involved patients who were male and aged 1 to 2 years. Although it has been suggested that pediatric minoxidil ingestions might result in serious adverse effects, this study suggests that most pediatric minoxidil exposures reported to poison centers are not likely to have serious outcomes and may be managed at home.

[The distribution of amlodipine in the organism of the warm-blooded animals]. / Raspredelenie amlodipina v organizme teplokrovnykh zhivotnykh.

The objective of the present study was to elucidate the specific features of amlodipine distribution in the organism of the warm-blooded animals (rats) following a single intragastric administration of the poisonous substance at a dose of 686 mg/kg b/w/ (LD50). Amlodipine was isolated from the blood and various organs of the animals by means of acetone extraction and purified on the silica gel column (100/160 mcm) with the elution by an ethanol-hexane (7:3) mixture. The identification and the quantitative measurement of amlodipine were performed with the use of the TLC, GC-M, and UV-spectrophotometry. The study has shown that unmetabolized amlodipine was present in large amounts in the internal organs and blood of the poisoned animals. The principal organs of its accumulation were the stomach, kidneys, and blood.

Adult clonidine overdose: prolonged bradycardia and central nervous system depression, but not severe toxicity.

CONTEXT: There are limited reports of adult clonidine overdose. We aimed to describe the clinical effects and treatment of clonidine overdose in adults. METHODS: This was a retrospective review of a prospective cohort of poisoned patients who took clonidine overdoses (>200 µg). Demographic information, clinical effects, treatment, complications (central nervous system and cardiovascular effects) and length of stay (LOS) were extracted from a clinical database or medical records. RESULTS: From 133 admissions for clonidine poisoning (1988-2015), no medical record was available in 14 and 11 took staggered ingestions. Of 108 acute clonidine overdoses (median age 27 years; 14-65 years; 68 females), 40 were clonidine alone ingestions and 68 were clonidine with co-ingestants. Median dose taken was 2100 µg (interquartile range [IQR]: 400-15,000 µg). Median LOS was 21h (IQR: 14-35 h) and there were no deaths. Glasgow coma score [GCS] <15 occurred in 73/108 (68%), and more patients taking co-ingestants (8/68; 12%) had coma (GCS <9) compared to clonidine alone (2/40; 5%). Miosis occurred in 31/108 (29%) cases. Median minimum HR was 48 bpm (IQR: 40-57 bpm), similar between clonidine alone and co-ingestant overdoses. There was a significant association between dose and minimum HR for clonidine alone overdoses (p = 0.02). 82/108 (76%) had bradycardia, median onset 2.5 h post-ingestion (IQR: 1.7-5.5 h) and median duration 20 h (2.5-83 h), similar for clonidine alone and co-ingestant overdoses. There were no arrhythmias. Three patients ingesting 8000-12,000 µg developed early hypertension. Median minimum systolic BP was 96 mmHg (IQR: 90-105 mmHg) and hypotension occurred in 26/108 (24%). 12/108 patients were intubated, but only 2 were clonidine alone cases. Treatments included activated charcoal (24), atropine (8) and naloxone (23). The median total naloxone dose was 2 mg (IQR: 1.2-2.4 mg), but only one patient given naloxone was documented to respond with partial improvement in GCS. DISCUSSION: Clonidine causes persistent but not life-threatening clinical effects. Most patients develop mild central nervous system depression and bradycardia. Naloxone was not associated with improved outcomes.

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.

Mixed amlodipine/valsartan overdose treated by the molecular adsorbent recirculating system (MARS™).

CASE REPORT: We describe the case of a 58-year-old woman who developed a severe distributive shock following the intentional ingestion of a large overdose of amlodipine (480 mg) combined with valsartan (3680 mg). Extreme vasoplegia remained refractory to maximal standard therapy including fluid resuscitation, intravenous calcium, vasopressors at very high doses, hyperinsulinemia-euglycemia therapy, lipid emulsion, and methylene blue administration. Besides, the patient exhibited hyperglycemia refractory to very high doses of insulin. Due to its theoretical ability to effectively remove protein-bound drugs such as amlodipine from the circulation, albumin dialysis with the molecular adsorbent recirculating system (MARS™) was performed during two consecutive sessions. Blood was drawn for toxicokinetic calculations. Amlodipine elimination half-life during the first MARS™ session was calculated at 7.6 h. In addition, there was a rapid fall in blood glucose, requiring the introduction of a continuous infusion of glucose in order to achieve euglycemia. Moreover, a few hours after the initiation of the MARS™ therapy, the hemodynamic status was not significantly modified but a significant tapering of epinephrine infusion was possible, together with a progressive decrease of blood lactate level. However, the need for vasopressors in decreasing doses was present until day 5 post-ingestion. Eventually, the patient fully recovered and was discharged home 8 days after admission. DISCUSSION: The role of the MARS™ in the treatment of severe poisoning of calcium channel blockers is still to be defined. We were able to demonstrate a relatively short elimination half-life of amlodipine. A decreased insulin resistance and a reduction of epinephrine infusion were also observed.

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.

[Clonidine poisoning in a child: a case report]. / Intoxication pédiatrique sévère avec une faible dose de clonidine : à propos d'un cas.

Clonidine poisoning's clinical feature is well documented in the medical literature, but the minimal toxic dose has not yet been established. The effectiveness of naloxone is also controversial. The authors describe a clonidine overdose in a 9-year-old boy (25 kg) during a growth hormone test: he received tenfold the prescribed clonidine dose (0.23 mg instead of 0.023 mg) with 6.2 mg betaxolol. About 40 min later, he became drowsy and then complained of low blood pressure, bradycardia, and myosis. By maintaining the Trendelenburg position, administering fluids as well as salbutamol and naloxone (three doses of 0.2 mg were required), he recovered and was discharged from the hospital on day 2. The minimal clonidine toxic dose, the clinical picture, and the effectiveness of naloxone administration are discussed in this paper.

Lipid emulsion use precluding renal replacement therapy.

BACKGROUND: Intralipid emulsion (ILE) is a nutritional fatty acid supplementation that is emerging as a potential therapy for local anesthetic systemic toxicity and is also being considered as a therapy for other lipophilic medication intoxications. Isolated reports of pulmonary edema or severe lipemia exist as a complication of therapy. CASE REPORT: A 26-year-old hypertensive, male, kidney transplant recipient presented to an outside emergency department (ED) after an intentional overdose of his medications (ie, amlodipine, metoprolol, lisinopril). At presentation, he had hypotension and bradycardia that was unresponsive to treatment with intravenous saline, calcium, glucagon, and vasopressors. After failure of conventional therapy, an initial bolus of ILE (20%) was given with some improvement in his heart rate, and the dose was repeated. A continuous intravenous infusion of ILE therapy was started. The patient deteriorated, with development of both acute respiratory and renal failure. Continuous venovenous hemofiltration (CVVHF) was attempted to remove volume and correct metabolic abnormalities. Lipemic blood was immediately observed in the CVVHF filter. After 15 min, the transmembrane pressures of the filter began to rise in the absence of observed clotting of the blood and the filter then became completely obstructed. An attempt was made to remove the lipid by plasmapheresis to restart CVVHF, but the patient continued to deteriorate despite maximal vasopressor support. The patient's family decided to withdraw care and the patient expired. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians treat patients with toxic ingestions on a regular basis. Being aware of possible complications of experimental antidote therapy, like ILE, can improve the treatment approach and outcomes for these patients.

Accidental overdose of travoprost.

PURPOSE: To report systemic symptoms after an overdose of travoprost. CASE REPORT: We report a patient who, instead of artificial tears, inadvertently used travoprost every 15 minutes for 7 hours after LASIK (laser-assisted in situ keratomileusis) surgery. She experienced abrupt, severe abdominal cramps and sudden, severe menstrual bleeding, which subsided quickly upon discontinuation of the drug. CONCLUSIONS: Because of the few systemic adverse effects, prostaglandin analogs are widely used for the treatment of glaucoma. Travoprost should be taken once daily; therefore, overdose is extremely uncommon. Systemic prostaglandins have been found to be mediators of uterine activity and are used to induce labor and terminate pregnancies. The high dose of this topical medication, as well as the compromised cornea, makes this case unique. The unusual circumstances observed in this case greatly expand our knowledge regarding the potential adverse effects of travoprost.

Extracorporeal life support and plasmapheresis in a case of severe polyintoxication.

BACKGROUND: Resuscitation without return to spontaneous circulation in patients with suicidal ingestion of cardiotoxic drugs necessitates alternative bridging therapies for drug removal. OBJECTIVES: To show the effectiveness of emergency extracorporeal membrane oxygenation (ECMO) and plasmaspheresis in severe polyintoxication. CASE REPORT: A 21-year-old woman developed asystole after suicidal polyintoxication with 1.75 g carvedilol, 300 mg amlodipine, 6 g amitriptyline, 500 mg torsemide, 1.5 g ketoprofen, 28 g nicotinic acid, and 16 g gabapentin. After 3 h of cardiopulmonary resuscitation without return to spontaneous circulation, ECMO was used as a bridging therapy and a temporary pacemaker was inserted. Plasma peak levels were measured for amlodipine (29.3 µg/L), amitriptyline (1456 µg/L), carvedilol (585 µg/L), and gabapentin (126.8 mg/L). To facilitate drug removal, therapeutic plasma exchange was performed. The patient could be weaned from ECMO at day 4 and extubated on day 8 after admission without neurologic sequelae. CONCLUSION: ECMO and plasma exchange should be considered as a therapeutic option in selected patients under resuscitation without return to spontaneous circulation after severe intoxication.