Angiotensin converting enzyme inhibitor intoxication: Naloxone to the rescue? Naloxone for ACE inhibitor intoxication.

We report here the case of a patient with perindopril intoxication inducing severe bradycardia together with a profound hypotension. Initiation of a naloxone infusion completely resolved those symptoms. As a consequence, we could recommend as a first step the use of naloxone in order to prevent the use of more invasive therapeutic tools.

Use of veno-venous extracorporeal membrane oxygenation to treat severe combined calcium channel blocker and angiotensin converting enzyme inhibitor overdose.

INTRODUCTION: Calcium channel blockers (CCBs) are a commonly prescribed medication that, at toxic levels, are capable of causing severe refractory hypotension, hypoxic respiratory failure and cardiotoxicity. There is little evidence currently guiding the approach to managing CCB overdose, particularly when combined with other antihypertensive agents. CASE REPORT: We describe the use of veno-venous extracorporeal membrane oxygenation (VV ECMO) in a previously healthy man following combined overdose with amlodipine and lisinopril in a suicide attempt. ECMO was used to provide oxygenation support, allowing for the amlodipine and lisinopril to be metabolized and cleared while also reducing ventilator-induced lung injury (VILI) and avoiding the complications associated with venous-arterial (VA) ECMO, such as differential hypoxemia. CONCLUSION: Limited case reports suggesting the use of ECMO in CCB overdose have employed VA ECMO due to CCB-induced cardiotoxicity. We believe that, if cardiac function has been preserved, VV ECMO should be considered a viable treatment strategy for CCB and ACE-I overdose resulting in refractory hypoxemic respiratory failure.

A 13-year review of lisinopril ingestions in children less than 6 years of age.

BACKGROUND: Lisinopril is an angiotensin converting enzyme inhibitor used for treatment of hypertension, congestive heart failure, and acute myocardial infarction. Reports of clinical experience with pediatric ingestions are minimal. METHOD: A 13-year retrospective study of lisinopril ingestions in children reported to the California Poison Control System was analyzed and case notes were reviewed. Institutional Review Board approval was obtained and cases were blinded. Inclusion criteria were lisinopril as a single ingestant, age less than 6 years, treatment in a health care facility, case followed to a known outcome. RESULTS: Inclusion criteria were met in 296 cases. Demographics include 51% of male patients and the mean age was 1.97 years (range: 9 months-5 years). Of the 296 patients, 8 patients (2.7%) developed hypotension (ranges: 55-74 mm Hg systolic and 22-48 mm Hg diastolic). The lowest blood pressure of 55/22 mm Hg was recorded in a 22-month old male who ingested an estimated 120-mg lisinopril (13.3 mg/kg). The lowest dose of lisinopril causing hypotension was with an estimated dose of approximately 50 mg or 3.9 mg/kg in a 2-year old. Two hundred and eighty-two patients (95.3%) were treated and released from the emergency department and 14 patients (4.7%) were admitted. The dose ingested was reported in 189 cases and an exact-dose of lisinopril was reported in 61 patients (20.6%); mean amount ingested was 3.0 mg/kg, median amount ingested was 2.1 mg/kg (range: 0.1-10.9 mg/kg, N = 38); and mean total dose was 33.4 mg, median total dose was 20 mg (range: 2.5-160 mg, N = 61). None of the patients with exact-dose lisinopril ingestions developed hypotension, received intravenous fluids, or were admitted. CONCLUSION: The lowest estimated dose of lisinopril to cause hypotension was 50 mg or 3.9 mg/kg. Although continued evaluation of pediatric lisinopril ingestions is essential to determine more specific thresholds of toxicity, the lack of effect on blood pressure in children with exact-dose ingestions indicate that pediatric lisinopril ingestions (for ages > 9 months) ≤ 4 mg/kg up to 40 mg total may be safely managed at home.

Successful treatment of suicide attempt by megadose of propafenone and captopril.

Intoxication caused by propafenone is very rare, and there is no case reported before propafenone and captopril intoxication together. There are few case reports in the literature about intoxication with more than 6 g of propafenone. We present the clinical manifestation and successfully treatment of 9 g of propafenone and 1 g captopril intoxication in an 18-year-old female. An 18-year-old female was brought to the emergency department approximately half an hour after she committed suicide with 30 propafenone tablets, 300 mg each, and 20 captopril tablets, 50 mg each. Her fist electrocardiography (ECG) shows a chaotic ventricular rhythm with a prolonged QRS complex. After fluid and sodium bicarbonate infusion and permanent pacemaker implantation, sinus rhythm was achieved. This case, to our knowledge, is the first in that it describes the successful recovery of a patient who ingested extensively large doses of propafenone (9 g) and captopril (1 g), both of which are known to have severe cardiac side effects.

[The use of extracorporeal life support and continuous venovenous haemodiafiltration in severe angiotensin converting enzyme inhibitor, calcium channel bloker and beta-blocker multidrug intoxication]. / Zastosowanie pozaustrojowego utlenowania krwi i wspomagania krazenia oraz ciaglej zylno-zylnej hemodiafiltracji w ciezkim zatruciu inhibitorem konwertazy, blokerem kanalu Ca++ i beta-blokerem.

Extracorporeal membrane oxygenation (ECMO) is an established method of treatment for extremely severe respiratory failure (ARDS, acute respiratory distress syndrome), for mechanical circulatory support after cardiac surgery as well as advanced resuscitation technique in specific cases. Severe multidrug poisoning causing an acute cardiovascular insufficiency combines all of these indications. We report a case of multiple drug poisoning: ACE inhibitor (ACE-I), beta-blockers and calcium channel blockers. Acute heart failure and multiorgan failure, have been successfully cured with the concomitant use of ECMO, hemodiafiltration and oscillatory ventilation.

Poisoning by illegal rodenticides containing acetylcholinesterase inhibitors (chumbinho): a prospective case series.

OBJECTIVE: To describe a prospective case series of poisonings caused by ingestion of illegal rodenticides containing acetylcholinesterase inhibitors, mainly "chumbinho," followed-up by the Campinas PCC for a period of 1 year. CASE SERIES: Seventy-six cases were included, of which 53.9% were males. Age ranged from 2 to 74 years (median = 36 years). The main circumstances leading to poisoning were intentional (suicide attempts 92.1%; homicide attempts 5.3%), and 65.8% were admitted less than 2 hours after ingestion. Most of the patients (96.1%) showed cholinergic muscarinic manifestations, particularly salivation (86.8%), myosis (77.6%), sweating (50%), and bronchorrhea (35.5%). Atropine was used in 82.9% of patients (median = 2 days), intubation and mechanical ventilation in 46.1% (median = 3 days), and the median length of the hospital stay was 4 days. Plasma samples obtained upon admission in 59 cases revealed (LC-MS/MS): aldicarb (55), carbofuran (2), aldicarb and carbofuran (1), no active component (1). In most of the plasma and urine samples collected upon admission, the highest concentrations (ng/mL) obtained were for the active metabolite aldicarb sulphoxide (plasma, median = 831, IIQ = 99.2-2885; urine, median = 9800, IIQ = 2000-15000) than aldicarb (plasma, median = 237, IIQ = 35.7-851; urine, median = 584, IIQ = 166-1230), indicating rapid metabolism. The excretion of aldicarb and its metabolites was rapid since these compounds were rarely detected in plasma samples 48 hours after admission. Sequential cholinesterase analysis in 14 patients revealed almost complete reactivation in the first 48 hours post-admission, compatible for poisoning by carbamates. Based on the Poisoning Severity Score, the cases were classified as asymptomatic (5.3%), minor (11.8%), moderate (35.5%), severe (43.4%), and fatal (3.9%). CONCLUSIONS: Most poisonings involved aldicarb and resulted from suicide attempts; the poisonings were generally severe, with a mortality of 3.9%. Aldicarb was rapidly absorbed, metabolized, and excreted.

[Intentional poisoning with ACE inhibitors. Emergeny Hospital Iasi]. / Toxicitatea acuta a inhibitorilor enzimei de conversie a angiotensinei. Experienta clinicii de medicina interna si toxicologie, spitalul clinic de urgente "SF Ioan" Iasi.

UNLABELLED: Regarding angiotensin-converting enzyme inhibitors (ACEI) poisoning, only few data are available in the last decade literature. In the previous couple of years especially isolated case reports were published. MATERIAL AND METHOD: We analyzed retrospectively all the patients with acute ACEI poisoning admitted in Iasi Internal Medicine and Toxicology Clinic between 2004 and 2009. RESULTS: 17 cases of poisoning were recorded (enalapril-9 cases, captopril-3 cases, perindopril-3 cases, lisinopril-2 cases). All the poisonings were intentional. A favorable outcome was consistently observed, and were recorded no sequelae or death in this study. The main complain was hypotension, required fluid administration, only one case with 500 mg enalaprilum and severe hypotension required injection of vasopressive amines. No abnormal renal function and no angioedema were noted.

Unintentional paediatric ingestions of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists.

AIMS: There is limited information on safety of angiotensin converting enzyme (ACE) inhibitors and angiotensin II (AII) receptor antagonists in unintentional paediatric ingestions. This study was conducted with the aim of developing referral guidelines for poison information centres. METHODS: Calls to the NSW poison information centre from January 2002 to July 2004 regarding paediatric ingestion of ACE inhibitors and AII receptor antagonists were recruited and prospectively followed up. Information collected included: demographics (age, gender, weight), type of exposure (unintentional, therapeutic error), ingested dose and clinical effects. Dose was reported in defined daily doses (DDD) to compare across and within the two drug classes with respect to the normal adult dose. RESULTS: Nineteen cases of paediatric ingestion of ACE inhibitors and AII receptor antagonists were included. The median age was 2 years (Interquartile range (IQR): 20-33 months) and the median dose ingested was 1 DDD (IQR: 1-2). There were nine ACE inhibitor ingestions and 10 AII receptor antagonist ingestions. One of nine children (11%) observed in hospital developed transient hypotension but required no treatment and recovered without complication. This child ingested an ACE inhibitor and ingested >3 DDD. CONCLUSION: Unintentional paediatric ingestions of ACE inhibitors and AII receptor antagonists resulted in the majority of children remaining asymptomatic. ACE inhibitor ingestions under 2 DDD can be observed at home provided the child is asymptomatic and there is a responsible adult to observe the child. The dose required for observation in AII receptor antagonist ingestions is less clear.

Pediatric lisinopril ingestions reported to Texas poison control centers.

Lisinopril is not recommended for use by young children. This study attempted to identify factors associated with serious outcomes in pediatric lisinopril ingestions. Cases for this study were lisinopril ingestions by children age < or =5 years reported to Texas poison control centers during 1998-2005. The percentage of cases involving serious medical outcomes was identified for selected variables and evaluated for statistical significance by calculating the rate ratio (RR) and 95% confidence interval (CI). Of 691 total cases, 26 (3.8%) involved a serious outcome. Higher serious outcome rates were found with a maximum dose of >4 mg/kg (RR: 2.54, CI: 0.05-25.62), or >80 mg (RR: 7.85; CI: 1.73-29.29), or five or more tablets (RR: 8.18; CI: 2.73-22.54), or the patient was already at or en route to a health care facility when the poison control center was contacted (RR: 13.93; CI: 3.68-77.78), or referred to a health care facility by the poison control center (RR: 33.49; CI: 9.04-194.94). The management of patients with severe outcomes was more likely to involve health care facilities. This information is useful for drafting triage guidelines for the management of pediatric lisinopril ingestions.

Rapid onset of haemodynamic effects after angiotensin converting enzyme-inhibitor overdose: implications for initial patient triage.

BACKGROUND: Angiotensin converting enzyme (ACE)-inhibitor overdose may result in severe hypotension. Existing data do not adequately deal with the likely onset of haemodynamic effects, which has implications for the appropriate duration of monitoring in the acute-care setting. Therefore, the relationship between the interval after an ACE-inhibitor overdose and onset of hypotension was examined. METHODS: A retrospective case review of patients who attended our institution after an ACE-inhibitor overdose between 1 January 2000 and 31 December 2005 was carried out. Data collected were heart rate, blood pressure, electrolytes, electrocardiogram variables, and interval between ingestion and lowest recorded blood pressure. RESULTS: 33 patients (24 men) who presented after an ACE-inhibitor overdose were identified. Median (interquartile range (IQR)) age was 49 (42-56) years, and stated quantity ingested was 20 (7-42) times the defined daily dose. The median (IQR) interval between ACE-inhibitor ingestion and lowest recorded systolic blood pressure was 4.5 (3.8-5.5) h, diastolic blood pressure was 3.8 (3.3-6.5) h and mean blood pressure was 4.2 (3.5-5.5) h. Heart rate did not increase substantially in response. CONCLUSION: The lowest blood pressure was recorded within a short interval after an ACE-inhibitor overdose, irrespective of therapeutic intervention. Patients in whom hypotension has not occurred within 6 h of ingestion can be considered for discharge.

[Vasopressin analogue injection as ultimate measure for counteracting severe catecholamine-refractory poisoning by several vasodilators taken with suicidal intent]. / Vasopressinanaloga als Ultima ratio bei einer schweren Intoxikation mit Vasodilatanzien.

HISTORY AND CLINICAL FINDINGS: A 78-year-old woman was admitted to the intensive care unit 9 hours after ingestion of 2 g of isosorbitmononitrate, 430 mg of amlodipine, 250 mg of benazepril and 600 mg of mirtazapin in suicidal intent. INVESTIGATIONS: Clinical findings and invasive monitoring showed signs of a hyperdynamic hemodynamic cardiovascular failure caused by toxic vasodilatation. TREATMENT AND COURSE: Despite of primary detoxication, intravenous volume infusion with calcium gluconate, glucagon and naloxone and administration (norepinephrine up to 2 micro g/kg/min) no hemodynamic stabilization was achieved. Only when the vasopressin-analogue argipressin was given peripheral vasodilatation was overcome and hemodynamic stabilization resulted. 10 hours after discontinuing argipressin and norepinephrine the patient developed a mesenteric ischemia, and she finally died on the third day after admission. CONCLUSION: In circulatory shock due to toxic vasodilatation the use of vasopressin analogue argipressin can be helpful as an ultima therapeutic measure in catecholamine refractory shock caused by vasodilatation. Attention must be paid to overwhelming vasoconstrictor effects resulting in mesenteric ischemia.

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.

Poisoning with anti-hypertensive drugs: angiotensin converting enzyme inhibitors.

The increase in the popularity of ACE inhibitors in the treatment of hypertension has resulted in increased use and availability of such drugs. For the majority of patients the effects from poisoning or overdosage are mild and close observation may be all that is required. When symptoms and signs are more profound hospital admission is indicated. Severe hypotension may require intravenous fluids and inotropic support.

[Drugs as a cause of death. A prospective quality assurance project in a department of medicine]. / Legemidler som årsak til dødsfall. Et prospektivt kvalitetssikringsprosjekt i en medisinsk avdeling.

This study is part of a prospective quality assurance project in a Norwegian county hospital. The major aims of the study were to estimate the number of drug-related deaths; assess whether these were recognized by the clinicians, and (if not) discuss why the clinicians had difficulties in recognizing drug-related deaths. A panel of two internists, one pathologist, one pharmacologist and one pharmacist evaluated all inpatients deaths over a six-month period. Among 3,082 hospitalized patients, 169 died. Of these deaths, 20 were classified as probably (nine) or possibility (11) drug-related. Only two of the deaths were recognized as such by the clinicians in the ward. The reasons for the clinicians failure to recognize adverse drug reactions include frequent presence of multiple diseases, polypharmacy and inadequate guidelines on how to look for adverse reactions to drugs. A two-year survey aimed at studying these aspects in depth is in progress.

Consequences of angiotensin-converting enzyme inhibitor overdose.

Overdose with angiotensin-converting enzyme (ACE) inhibitors is still a relatively underreported phenomenon. We report here a case of an unintentional overdose of enalapril (100 mg) together with other medications. The patient experienced no adverse consequences. Pharmacokinetic evaluation revealed a t 1/2 for enalaprilat (prodrug) of seven hours and for enalapril at 36 hours. Based on this case report as well as others, guidelines for assessment and treatment of these patients are proposed. Management of hypotension is the primary therapeutic intervention.