Intravenous Lipid Emulsion does NOT have a role in severe poisoning: CON.

Intravenous lipid emulsion (ILE) has been suggested as a potential universal antidote for cardiovascular and central nervous system toxicity resulting from a multitude of pharmaceutical and nonpharmaceutical poisonings. While there is some evidence to suggest that ILE may have a positive effect in cardiovascular system toxicity after accidental intravenous lipophilic local anaesthetic overdose, this cannot be extrapolated to cases of severe poisoning resulting from oral drug overdose. Treatment recommendations are based upon variable outcome animal studies and low-level clinical evidence with a significant degree of positive reporting bias. Currently, there is a paucity of controlled clinical data to support ILE use to treat severe drug poisoning after oral overdose. ILE use should be limited to well-designed, ethically approved, controlled clinical trials aimed at determining the true effectiveness of this therapy. This should replace the current scattergun clinical use in a multiplicity of poisoning scenarios and subsequent anecdotal reporting approach.

Elderly patients with suspected chronic digoxin toxicity: A comparison of clinical characteristics of patients receiving and not receiving digoxin-Fab.

OBJECTIVE: The aim of the present study was to compare clinical features of patients with elevated serum digoxin concentrations who were treated with digoxin-Fab with those where the immunotherapy was not given by a tertiary hospital toxicology service. METHODS: This was a retrospective series of patients with supratherapeutic serum digoxin concentrations referred to the toxicology service from August 2013 to October 2015. Data collected included demographics, presenting complaint, digoxin dose, other medications taken, serum digoxin, potassium and creatinine concentration on presentation and initial and post-digoxin-Fab heart rate. RESULTS: There were 47 referrals. Digoxin-Fab was administered in 21 cases. It was given more commonly when the heart rate was <51/min or serum potassium was >5.0 mmol/L. Patients receiving digoxin-Fab were more likely to be on maintenance therapy with beta-blockers or calcium channel blockers (95% vs 61%; OR 13.1; 95% CI 1.5-113) and/or potassium-sparing medications (95% vs 54%; OR 17.1; 95% CI 2.0-147). They had elevated serum creatinine (76% vs 42%; OR 8.2; 95% CI 1.9-34), higher serum potassium (median: 5.1 mmol/L vs 4.2 mmol/L, P = 0.02), higher serum digoxin concentration (median: 3.5 nmol/L vs 2.3 nmol/L, P = 0.02) and pretreatment heart rate <51/min (66% vs 31%; OR 4.5; 95% CI 1.3-15). There were no patients with ventricular arrhythmias or hypotension. Median heart rate increased by 10/min 1 and 4 h after digoxin-Fab. However, individual heart rate response to digoxin-Fab was variable. CONCLUSION: Digoxin-Fab was more commonly administered when heart rate was <51/min. It had a small effect on increasing heart rate; however, individual response to digoxin-Fab was variable as patients were using other negative chronotropic medications. In symptomatic bradycardic patients on multiple heart failure medications, positive chronotropic and potassium-lowering therapies should be considered in concert with digoxin-Fab.

Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies.

Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs can also produce vasodilatory shock. Additionally, CCBs, such as verapamil and diltiazem, are commonly ingested in sustained-release formulations. This can also be the case for some BBs. Peak toxicity can be delayed by several hours. Provision of early gastrointestinal decontamination with activated charcoal and whole-bowel irrigation might mitigate this. Treatment of shock requires a multimodal approach to inotropic therapy that can be guided by echocardiographic or invasive haemodynamic assessment of myocardial function. High-dose insulin euglycaemia is commonly recommended as a first-line treatment in these poisonings, to improve myocardial contractility, and should be instituted early when myocardial dysfunction is suspected. Catecholamine infusions are complementary to this therapy for both inotropic and chronotropic support. Catecholamine vasopressors and vasopressin are used in the treatment of vasodilatory shock. Optimizing serum calcium concentration can confer some benefit to improving myocardial function and vascular tone after CCB poisoning. High-dose glucagon infusions have provided moderate chronotropic and inotropic benefits in BB poisoning. Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which can limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock.

Intrathecal Clonidine Pump Failure Causing Acute Withdrawal Syndrome With 'Stress-Induced' Cardiomyopathy.

Clonidine is a central alpha(2)-agonist antihypertensive used widely for opioid/alcohol withdrawal, attention deficit hyperactivity disorder and chronic pain management. We describe a case of clonidine withdrawal causing life-threatening hypertensive crisis and stress-induced cardiomyopathy. A 47-year-old man with chronic back pain, treated with clonidine for many years via intrathecal pump (550 mcg/24 h), presented following a collapse and complaining of sudden worsening of back pain, severe headache, diaphoresis, nausea and vomiting. A few hours prior to presentation, his subcutaneous pump malfunctioned. On presentation, vital signs included pulse 100 bpm, BP 176/103 mmHg, temperature 37.8 °C and O2 saturation 100 % (room air). Acute clonidine withdrawal with hypertensive crisis was suspected. Intravenous clonidine loading dose and a 50 mcg/h infusion were commenced. Five hours later, severe chest pain, dyspnoea, tachycardia, hypoxia, with BP 180/120 mmHg and pulmonary edema ensued. ECG showed sinus tachycardia with no ST elevation. Repeated intravenous clonidine doses were given (25 mcg every 5-10 min), with ongoing clonidine infusion to control blood pressure. Glyceryl trinitrate infusion, positive pressure ventilation and intravenous benzodiazepines were added. Bedside echocardiogram showed stress-induced cardiomyopathy pattern. Serum troponin-I was markedly elevated. His coronary angiography showed minor irregularities in the major vessels. Over the next 3 days in the ICU, drug infusions were weaned. Discharge was 12 days later on oral clonidine, metoprolol, perindopril, aspirin and oxycodone-SR. Two months later, his echocardiogram was normal. The intrathecal pump was removed. We report a case of stress-induced cardiomyopathy resulting from the sudden cessation of long-term intrathecal clonidine. This was managed by re-institution of clonidine and targeted organ-specific therapies.

What are the adverse effects associated with the combined use of intravenous lipid emulsion and extracorporeal membrane oxygenation in the poisoned patient?

CONTEXT: Intravenous lipid emulsion (ILE) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are being used together or in close succession in the management of circulatory failure secondary to cardiotoxic drug poisoning. There have been reports of mechanical problems, including fat emulsion agglutination, clogging, increased blood clot formation and even cracking of parts of the machine, in patients concurrently receiving VA-ECMO and ILE as part of parenteral nutrition. OBJECTIVE: To ascertain the adverse effects associated with the combined use of ILE and ECMO in the poisoned patient. METHODS: PubMed and OVID (1966 to 9 June 2014) and EMBASE (1947 to 9 June 2014) were searched to identify publications relating to studies and/or case reports where ILE had been used at the same time when VA-ECMO was used - 7 were identified. In addition, the abstracts published between 2006 and 2013 inclusive of those from the North American Congress of Clinical Toxicology and the congresses of the European Association of Poisons Centres and Clinical Toxicologists were searched to identify additional cases and 2 were found. Finally all cases posted on lipidrescue.org were reviewed to determine if they related to the use of ILE with VA-ECMO and no new cases were identified. In vitro study. An in vitro study involving the continuous infusion of 20% ILE at 3 mL/h for 24 h demonstrated layering (separation of intact fat emulsion from blood) and agglutination (clumping resulting in little or no flow of fat emulsion through the circuit) in all circuits within 30 min of starting the fat emulsion infusion. CLINICAL STUDIES: An observational study based in 42 centres that regularly used 'fat emulsion' during VA-ECMO treatment reported cracking of stopcocks (the valve which restricts flow in the VA-ECMO tubing) (n = 10, 23.8%); fat emulsion agglutination (n = 11, 26.2%); clogging and associated malfunction of the membrane oxygenator (n = 2, 4.8%); and increased blood clot formation in the circuits (n = 2, 4.8%). In a prospective observational study of 9 neonates on VA-ECMO receiving intravenous nutrition, layering and agglutination were seen in four sets of VA-ECMO tubing and blood clots were found in seven circuits. Nine case reports were identified where ILE was used with VA-ECMO for the management of circulatory failure/instability secondary to cardiotoxic drug poisoning. In two of these case reports, the authors specifically stated that ILE did not cause any mechanical complications with the VA-ECMO; the other seven reports made no comment as to whether there were any complications or not. CONCLUSIONS: There is in vitro and clinical evidence that the combined use of ILE and extracorporeal membrane oxygenation may be associated with fat deposition in the VA-ECMO circuits and increased blood clot formation. Clinicians managing poisoned patients with both of these novel treatment modalities should be aware of these potential complications.

Acute toxicity associated with analytically confirmed recreational use of methiopropamine (1-(thiophen-2-yl)-2-methylaminopropane).

PURPOSE: Methiopropamine use in Europe has been detected since January 2011, but there is limited information on its acute toxicity. Here, we describe a case of analytically confirmed methiopropamine acute toxicity. CASE REPORT: A 27-year-old woman with no previous medical history was brought to the emergency department with palpitations, chest tightness, anxiety, nausea, vomiting and visual hallucinations following the use of a 'Quicksilver'. Toxicological analysis of her urine collected at presentation to the ED detected methiopropamine at a concentration of 400 ng/mL. Other drugs were also detected but at a much lower concentration. CONCLUSION: This is the first ever case report of analytically confirmed acute toxicity related to methiopropamine use. It confirms the potential for significant acute toxicity with cardiovascular, gastrointestinal and psychotic symptoms thus providing further information to help with managing these patients and allow legislative authorities to consider the need for its control.

Acute indoramin poisoning: a review of 55 cases reported to the Paris Poison Centre from 1986 t o 2010.

Authors report a retrospective study of all cases of indoramin-only poisoning notified to the Paris poison Centre from 1986 to 2010. Fifty five cases of indoramin self-poisoning were included: 40 adults and 15 children. The mean supposed ingested dose was about 701 mg±464 mg. ECG showed a prolonged QTc interval (equal to or greater than 0.50 s) in 30% of patients. The lowest observed dose for prolonged QTc was 625 mg. This series includes two cases of seizures occurring around two hours after ingestion of 900 and 2 250 mg of indoramin. A review of the literature showed cardiac disorders, with a delayed mechanism of action up until 18 hours after ingestion. Therefore, rapid medical resuscitation and prolonged cardiac monitoring for at least 24 hours after ingestion of 625 mg are recommended.

Occupational rhinitis and asthma due to EDTA-containing detergents or disinfectants.

BACKGROUND: Detergents and disinfectants are an emerging cause of work-related rhinitis and asthma. These products may contain ethylenediamine tetraacetic acid (EDTA). The authors report 10 cases of EDTA-related asthma and/or rhinitis. METHODS: Review of the medical charts of patients who presented with work-related rhinitis (alone or with asthma), with a history of exposure to aerosols of EDTA-containing products and who underwent a nasal provocation test (NPT) with tetrasodium EDTA (1-4%) in our occupational health unit. RESULTS: Twenty-eight patients underwent a NPT with EDTA, which was positive in 10 cases. These patients, mostly cleaners or healthcare workers, used spray formulations of cleaning products. CONCLUSIONS: This case series is the first report of EDTA-related respiratory disease, documented by a specific test. An irritant mechanism is unlikely. Further studies are required to distinguish between an immunoallergic response and a pharmacological mechanism possibly resulting from calcium chelation, as suggested by animal experiments. A ban of spray preparations would be sufficient to prevent respiratory disease induced by EDTA inhalation, regardless of its mechanism.

[Not Available]. / Acute Indoramin Poisoning: a Review of 55 Cases Reported to the Paris Poison Centre from 1986 to 2010.

Authors report a retrospective study of all cases of indoramin-only poisoning notified to the Paris poison Centre from 1986 to 2010. Fifty five cases of indoramin self-poisoning were included: 40 adults and 15 children. The mean supposed ingested dose was about 701mg±464mg. ECG showed a prolonged QTc interval (equal to or greater than 0.50s) in 30% of patients. The lowest observed dose for prolonged QTc was 625mg. This series includes two cases of seizures occurring around two hours after ingestion of 900 and 2 250mg of indoramin. A review of the literature showed cardiac disorders, with a delayed mechanism of action up until 18hours after ingestion. Therefore, rapid medical resuscitation and prolonged cardiac monitoring for at least 24hours after ingestion of 625mg are recommended.

Clinical significance of initial troponin I in the grey zone in emergency department chest pain patients: a retrospective pilot study.

AIM: 'Normal' range for cardiac troponin I (TnI) has changed with more sensitive tests, but the validity of low-level elevations is contentious. We aimed to describe the characteristics and outcome of patients with an initial TnI level 1-5 times the upper limit of normal. METHODS: Retrospective study of patients assessed for ACS with initial TnI level between 0.05-0.19 ng/ml. Data collected included demographics, clinical data, TnI levels and outcome. Primary outcome was the proportion of patients who had a serial TnI rise consistent with ACS. RESULTS: 72 patients were studied; median age 71, median TIMI score 3, 66.7% male. 35 patients (48.6%) had a TnI rise consistent with ACS. CONCLUSION: Approximately half of patients with initial TnI between 0.05-0.19 ng/ml had a TnI rise consistent with ACS. An initial TnI in this range is not, of itself, indicative of ACS. Clinical decision-making should be guided by clinical features and serial TnI measurement.