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.

Hemodynamically unstable: accidental atenolol toxicity?

BACKGROUND: Antihypertensive medications, including ß-blockers, are widely used in patients with chronic kidney disease. Unlike most ß-blockers, atenolol is excreted primarily by the kidney, and its clearance by peritoneal dialysis is poor. These pharmacokinetic factors may predispose patients to gradual accumulation of the drug over time. OBJECTIVES: To review the management of a diagnostic dilemma, the role of glucagon therapy, and the clinical implications of atenolol clearance. CASE REPORT: A young woman with end-stage renal disease requiring peritoneal dialysis presented with sudden onset of abdominal pain and hemodynamic instability with hypotension and relative bradycardia. The patient reported that she took her regular four antihypertensive agents, including atenolol, with no excess ingestion or recent dose changes. After resuscitation and consideration of a broad differential diagnosis, the most likely cause of the patient's illness was determined to be unintentional atenolol toxicity, with secondary mesenteric ischemia due to a low-flow state that caused her abdominal pain. Glucagon therapy led to rapid correction of the patient's hemodynamic instability and pain. CONCLUSION: The unique pharmacokinetics of long-term medications must be considered in patients with impaired clearance, such as this patient with end-stage renal disease treated by peritoneal dialysis. Medications may gradually accumulate to supratherapeutic levels, which over time may lead to symptoms of significant toxicity.

Case report: atenolol overdose successfully treated with hemodialysis.

Owing to the drug's favorable hydrophilic and pharmacokinetic characteristics, a number of case reports have demonstrated effective treatment of atenolol overdose with hemodialysis. However, the efficiency of atenolol clearance throughout hemodialysis treatments has not previously been examined. In this report, a patient with impaired renal function was successfully treated with two 5-hour intermittent high-flux high-efficiency hemodialysis therapies after atenolol overdose. Serial atenolol levels were measured during his hemodialysis treatments. We observed an over 50% plasma atenolol concentration reduction after each 5-hour hemodialysis therapy. Hemodialysis therapy is an effective treatment for atenolol overdose, especially in patients with impaired renal function.

Acute fatal poisoning with pilsicainide and atenolol.

A fatal case of intentional poisoning with two antiarrhythmic agents, pilsicainide, a pure sodium channel blocker, and atenolol, a selective beta1 blocker, is presented. A woman in her twenties was found dead at home and empty pill packages of pilsicainide, atenolol, and aspirin were found near by. Hesitation marks were found on the wrist, and strong fibrous degeneration was observed in the cardiomyocytes of the sinoatrial node. The blood concentrations of pilsicainide and atenolol were 7.83 and 4.94 microg/ml, respectively, both far above the reported therapeutic levels. According to these results, we concluded that death was due to cardiac arrhythmia caused by poisoning with pilsicainide and atenolol. This is the first report of fatal poisoning attributable to an overdose of the combination of these two antiarrhythmic drugs.

Successful treatment of a massive atenolol and nifedipine overdose with CVVHDF.

The aim of this paper was to describe a case of massive atenol and nifedipine poisoning, complicated by the co-existence of liver cirrhosis, where standard therapies (fluid replacement, vasopressors and inotropic agents, insulin, glucagon, calcium and bowel decontamination) were ineffective in restoring an adequate heart rate, blood pressure, renal and intestinal blood flow. This led to consequent anuric renal insufficiency and incipient multiple organ failure syndrome (MOFS). The patient recovered completely after Continuous Veno-Venous Hemo-Dia-Filtration (CVVHDF); this treatment removed atenolol from blood, with predicted clearance levels. The patient was a 45-year old female with a history of hypertension, liver cirrhosis, neurological and psychiatric disorders, with a massive atenolol (69.6 microg/mL) and nifedipine (63 ng/mL) overdose. CVVHDF at an ultrafiltration rate of 1 500 mL/h was started on day 1. From day 2 onwards, as the plasma atenolol concentration decreased, the blood pressure rose at a slow but constant rate. On day 5, there was restoration of an adequate blood pressure, which restored both renal and intestinal function, and also improved MOFS. The standard therapeutic approach was ineffective at eliminating both substances from the blood, and the clinical picture became worse due to incipient MOFS. CVVHDF was used in order to maintain the fluid and electrolyte balance and also to clear the beta blocker from the blood. The clearance kinetics of atenolol were consistent with the expected clearance values, on the basis of a CVVHDF ultrafiltration flow of 1 500 mL/h, which corresponds to a creatinine clearance of about 25 mL/min.

Hyperinsulinemic-euglycemic therapy for intoxication with calcium channel blockers.

Conventional therapy for intoxication with calcium channel blockers consists of crystalloid solutions, calcium gluconate, glucagon and vasopressor agents. These therapies often fail to improve hemodynamic function in intoxicated patients. The pathophysologic mechanism proposed for intoxication with these agents, suggest hypoinsulinemia as the determinant factor. We will describe the case of a 77 years old man treated for an overdose of nifedipine and atenolol who arrived at our institution with hypotension and bradycardia. After conventional therapy failed to improve the patient's hemodynamic status, hyperinsulinemia and euglycemia contributed to the improvement of the patient's neurologic and hemodynamic condition. Thus, hyperinsulinemic-euglycemic therapy was of benefit in this patient with hemodynamic compromise secondary to intoxication with calcium channel blocker not responding to conventional therapy. We will review the mechanism of action of calcium channel blocker drugs as well as the clinical presentation and treatment options for calcium channel blocker intoxication.

Hyperinsulinemic-euglycemic therapy for intoxication with calcium channel blockers

Conventional therapy for intoxication with calcium channel blockers consists of crystalloid solutions, calcium gluconate, glucagon and vasopressor agents. These therapies often fail to improve hemodynamic function in intoxicated patients. The pathophysologic mechanism proposed for intoxication with these agents, suggest hypoinsulinemia as the determinant factor. We will describe the case of a 77 years old man treated for an overdose of nifedipine and atenolol who arrived at our institution with hypotension and bradycardia. After conventional therapy failed to improve the patient's hemodynamic status, hyperinsulinemia and euglycemia contributed to the improvement of the patient's neurologic and hemodynamic condition. Thus, hyperinsulinemic-euglycemic therapy was of benefit in this patient with hemodynamic compromise secondary to intoxication with calcium channel blocker not responding to conventional therapy. We will review the mechanism of action of calcium channel blocker drugs as well as the clinical presentation and treatment options for calcium channel blocker intoxication.

Successful treatment with enoximone for severe poisoning with atenolol and verapamil: a case report.

Combined poisoning with calcium channel blockers (CCBs) and beta-blockers is usually associated with severe hypotension and heart failure. Due to the block of the beta receptors, treatment with adrenergic agonists, even at high doses, can be insufficient, and beta-independent inotropes, such as glucagon, may be required. Phosphodiesterase III (PDEIII) inhibitors represent a possible alternative to glucagon in these cases as they have an inotropic effect which is not mediated by a beta receptor.

Cardiovascular depression resulting from atenolol intoxication.

A case of massive atenolol ingestion leading to hypotension in association with PR and QRS interval prolongation on the electrocardiogram is presented. These clinical findings are identical to those attributed to the membrane-stabilizing activity of propranolol and other lipophilic beta-blockers. It is commonly believed that hydrophilic agents such as atenolol lack this activity. A review of the literature reveals that hydrophilic beta-blockers may have membrane-stabilizing activity, though much higher concentrations are required to produce this action in comparison with lipophilic agents. This case and a review of the literature provides a potential pathophysiological basis for atenolol-induced haemodynamic depression.

Aminophylline reversal of antihypertensive agent toxicity.

Hypotension occurred following a combined beta blocker (atenolol), angiotensin converting enzyme inhibitor (quinapil) and selective serotonin reuptake inhibitor (fluvoxamine) overdose. In another instance heart block and hypotension was noted in association with a diltiazem and atenolol adverse interaction. Crystalloid infusion was ineffective in both cases, but toxicity was rapidly reversed with aminophylline administration. Aminophylline's recognized inotropic and chronotropic properties make it a potentially valuable therapeutic agent in the treatment of antihypertensive medication toxicity.

[Two complex suicidal poisonings with drugs and their medicolegal aspects]. / Dwa kompleksowe samobójcze zatrucia lekami w aspekcie orzecznictwa sadowo-lekarskiego.

The main subject of the study was a toxicological investigation of biological specimens coming from two cases of intoxication with mixture of drugs. Two young people decided to commit suicide by the use of mixture of drugs mainly analgesic in approximately equal doses. For one person the dose of drugs administered turned out to be fatal while second person survived with the symptoms of acute intoxication. The analysis carried out with the use of liquid chromatographic method with mass detection (HPLC/MS) confirmed the presence of mixture of drugs in blood of living person and in postmortem specimens of the victim in significant concentrations. The toxicological findings have delivered information for discussion in medico-legal and ethical aspects.

Severe atenolol and diltiazem overdose.

CASE REPORT: A case of combined, massive overdose of both atenolol and diltiazem in an adult male is reported. Cardiac arrest ensued which was responsive to cardiopulmonary resuscitation. Bradycardia, hypotension, and oliguria followed which were resistant to intravenous pacing and multiple pharmacologic interventions, including intravenous fluids, calcium, dopamine, dobutamine, epinephrine, prenalterol, and glucagon. Adequate mean arterial pressure and urine output were restored only after addition of phenylephrine to therapy with multiple agents and transvenous pacing. The patient survived until discharge after a hospital course complicated by nontransmural myocardial infarct on hospital day 4 and pneumonia. Laboratory testing subsequently revealed high serum levels of both atenolol and diltiazem. The atenolol level of 35 microg/mL in this patient is the highest reported associated with survival. CONCLUSION: This case illustrates severe cardiovascular toxicity after overdose of both atenolol and diltiazem. Oliguria, which has previously been reported in severe atenolol overdose, was successfully treated without hemodialysis by the addition of phenylephrine to aggressive therapy with pacing, inotropic, and pressor support.

Factors influencing the degree and outcome of acute beta-blockers poisoning.

Since severe and fatal poisoning with beta-blockers due only to beta-receptor blockade is unlikely, a prospective and partly retrospective analysis of 67 patients with beta-blockers poisoning was done in five-year period in order to determine the factors influencing the degree and outcome of acute poisoning. According to pharmacological properties of drugs, the patients were divided in groups: group I--50 patients with propranolol, group II-A--10 patients with atenolol and group II-B--7 patients with metoprolol poisoning. Electrocardiogram (ECG), 24-h ECG monitoring, toxicological screening (determination of beta-blockers in blood, urine and lavage by high performance liquid chromatography) and biochemical analysis were performed in all patients. Significantly smaller number of patients with serious poisoning was observed in group II-B. Patient's age did not correlate with the degree of poisoning, but significant correlation was found between preexisting disease, ingested dose and the time elapsed before the treatment started. Analysis of pharmacological properties showed that membrane stabilizing activity and lipophilicity of the drug might be the important determinants of the toxicity, while the role of cardioselectivity was lost in an overdose.

Insulin-glucose as adjunctive therapy for severe calcium channel antagonist poisoning.

CASE REPORT: This case series documents the clinical courses of 4 patients after verapamil overdose and 1 patient after amlodipine-atenolol overdose. All subjects had hypodynamic circulatory shock (hypotension, bradycardia, and acidosis) that was not adequately responsive to conventional treatment. After initiation of insulin-dextrose infusion, the hemodynamic status of all 5 patients stabilized and all patients survived. Plasma drug concentrations are reported for all cases and verapamil levels were extremely high in 2 patients (3710 ng/mL and 3980 ng/mL). However, because patients were not treated according to a standard protocol, each patient received variable other supportive measures and inotropic agents, and the infusion rates of insulin were variable among patients. This report provides preliminary evidence toward a larger trial of insulin-dextrose to treat hypodynamic shock from calcium channel blocker overdose.

Electromechanical dissociation 48 hours after atenolol overdose: usefulness of calcium chloride.

Electromechanical dissociation (EMD) occurred in a 20-year-old woman 48 hours after an overdose of atenolol, despite intensive treatment of the beta-blocker poisoning (gastric lavage, charcoal, glucagon, epinephrine, atropine, correction of electrolyte abnormalities, administration of fluids, cardiac pacing, and mechanical ventilation). Administration of calcium chloride during EMD repeatedly restored blood pressure. Therefore it may have a role to play in management of atenolol overdose.

Combined overdose with verapamil and atenolol: treatment with high doses of adrenergic agonists.

A 55-year-old man was admitted following an overdose of sustained-release verapamil (calcium channel blocker) and ordinary-release atenolol (beta-1 blocker). At admission, there was extreme bradycardia (20-25 beats min-1) and hypotension (systolic arterial pressure 40-50 mm Hg). To counteract the cardiovascular depression, prenalterol, dopamine, dobutamine, isoprenaline, adrenaline and noradrenaline were used. A satisfactory state was obtained with adrenaline, noradrenaline and dopamine infused at high rates. Cardiac output was then more than 101 min-1, with a very low total peripheral resistance. The infusion of the adrenergic agonists could be interrupted on day 3. Prolonged ventilator treatment was necessary but the patient recovered without sequelae. Treatment options for similar cases are outlined.

Relative toxicity of beta blockers in overdose.

OBJECTIVE: To compare the toxicity of beta blockers in overdose and to identify clinical features predictive of serious toxicity. DESIGN: Comparison of clinical data collected prospectively on a relational database of subjects presenting to hospital with self-poisoning, coroner's data and prescription data. SETTING: Newcastle and Lake Macquarie, Australia, 1987-1995. MAIN OUTCOME MEASURES: Death, seizure, cardiovascular collapse, hypoglycemia, coma and respiratory depression. SUBJECTS: Fifty-eight self-poisonings with beta blockers and two deaths investigated by the coroner with evidence of propranolol poisoning. RESULTS: All patients who developed toxicity did so within six hours of ingestion. The use of ipecac was temporally associated with cardiorespiratory arrest in one patient. Propranolol was the only beta blocker associated with seizure; of those who ingested more than 2 g of propranolol, two thirds had a seizure. There was a significant association between a QRS duration of > 100 ms and risk of seizures. Propranolol was over represented in beta blocker poisoning when prescription data were also examined. Propranolol was the only beta blocker associated with death. Propranolol was taken by a younger age group. CONCLUSIONS: Propranolol should be avoided in patients at risk of self-poisoning. Propranolol poisonings should be observed closely for the first six hours post ingestion. Syrup of ipecac should not be used to decontaminate the gastrointestinal tract after beta blocker overdose.