Review article: Intravenous lipid emulsion as antidote: A summary of published human experience

Intravenous lipid emulsion (ILE) has been demonstrated to be effective in amelioration of cardiovascular and central nervous system sequelae of local‐anaesthetic and non‐local‐anaesthetic drug toxicity in animal models. Sequestration of lipophilic toxins to an expanded plasma lipid phase is credited as the predominant beneficial mechanism of action of ILE. Systematic review of published human experience is however lacking. We determined to report a comprehensive literature search of all human reports of ILE application in drug poisoning. Forty‐two cases of ILE use (19 local‐anaesthetic, 23 non‐local‐anaesthetic) were identified, with anecdotal reports of successful resuscitation from cardiovascular collapse and central nervous system depression associated with ILE administration in lipophilic toxin overdose. Although significant heterogeneity was observed in both agents of intoxication, and reported outcomes; case report data suggest a possible benefit of ILE in potentially life‐threatening cardio‐toxicity from bupivacaine, mepivacaine, ropivacaine, haloperidol, tricyclic antidepressants, lipophilic beta blockers and calcium channel blockers. Further controlled study and systematic evaluation of human cases is required to define the clinical role of ILE in acute poisonings.     

Accidental colchicine overdose. A case report and literature review

Colchicine overdose is uncommon but potentially life threatening. It is a safe drug when used according to established therapeutic guidelines but causes serious systemic effects if ingested in doses that exceed the recommendations. Overdose must therefore be recognised early and treated appropriately to optimise the outcome. A fatal case of colchicine overdose caused by inappropriate self medication is reported and to the best of the authors' knowledge, there has been no report of fatal accidental overdose in the United Kingdom. The pharmacology of colchicine, the clinical features associated with overdose, and the options for treatment are discussed.     

A Case of Near-fatal Flecainide Overdose in a Neonate Successfully Treated with Sodium Bicarbonate

Background

Flecainide is a class IC antidysrhythmic primarily indicated for ventricular dysrhythmias and supraventricular tachycardia (SVT). Class IC antidysrhythmic overdose has a reported mortality of 22%, and death results from dysrhythmias and cardiovascular collapse. We report a near-fatal flecainide overdose in an 18-day-old treated successfully with sodium bicarbonate.

Case Report

An 18-day-old, 2 weeks premature, 4-kg boy developed persistently high heart rates (220–240 beats/min) and electrocardiographic changes consistent with SVT. There was minimal response to vagal maneuvers, adenosine, and esmolol, and a transthoracic echocardiogram showed no underlying structural abnormality. The patient was then started on flecainide 4 mg orally every 8 h (Q8h). After the fourth dose he developed lethargy, cold clammy skin, and a heart rate of 40 beats/min with no palpable pulse. The patient was given 0.1 mg of atropine intravenously, with an increase of the heart rate to 160 beats/min. The child’s cardiac monitor revealed a wide-complex tachycardia with left bundle branch morphology, with associated pallor and poor capillary refill. Sodium bicarbonate was administered intravenously due to suspected flecainide toxicity. Approximately 5 min after intravenous administration of 10 mEq of 8.4% sodium bicarbonate twice, his rhythm converted to a narrow-complex tachycardia. A serum flecainide concentration was 1360 μg/L (therapeutic, 200–1000 μg/L) drawn 1 h before the cardiac arrest. It was later discovered that a twofold dosing error occurred: the patient received 8 mg Q8h instead of 4 mg Q8h for four doses.

Conclusion

Flecainide toxicity in children is rare, especially in neonates. It is important for clinicians to be able to identify and treat this uncommon poisoning.     

Intravenous fat emulsion therapy for intentional sustained-release verapamil overdose

We report the first case of sustained-release verapamil toxicity treated with Intralipid fat emulsion (IFE). Toxicity was confirmed by elevated serial serum verapamil and metabolite, norverapamil, levels. Most previously reported cases of IFE therapy involve local anaesthetic toxicity and cardiac arrest. Our patient was in shock despite standard therapy. No adverse events were noted and the patient fully recovered.     

Determining the Optimal Dose of Intravenous Fat Emulsion for the Treatment of Severe Verapamil Toxicity in a Rodent Model

Objectives: Recent animal studies have shown that intravenous fat emulsion (IFE) increases survival and hemodynamics in severe verapamil toxicity. However, the optimal dose of IFE is unknown. The primary objective was to determine the optimal dose of IFE based on survival in severe verapamil toxicity. Secondary objectives were to determine the effects on hemodynamic and metabolic parameters. The hypothesis was that there is a dose‐dependent effect of IFE on survival until a maximum dose is reached. Methods: This was a controlled dose‐escalation study. Thirty male rats were anesthetized, ventilated, and instrumented to record mean arterial pressure (MAP) and heart rate (HR). Verapamil toxicity was achieved by a constant infusion of 15 mg/kg/hr. After 5 minutes, a bolus of 20% IFE was given. Animals were divided into six groups based on differing doses of IFE. Arterial base excess (ABE) was measured every 30 minutes. Data were analyzed with analysis of variance. Results: The mean survival time for each dose of IFE was 0 mL/kg = 34 minutes, 6.2 mL/kg = 58 minutes, 12.4 mL/kg = 63 minutes, 18.6 mL/kg = 143.8 minutes, 24.8 mL/kg = 125.6 minutes, and 37.6 mL/kg = 130 minutes. Post hoc testing determined that the 18.6 mL/kg dose resulted in the greatest survival when compared to other doses. It increased survival 107.2 minutes (p = 0.004), 91.2 minutes (p = 0.001), and 80.8 minutes (p = 0.023) when compared to the lower doses of 0, 6.2, and 12.4 mL/kg, respectively. There was no added benefit to survival for doses greater than 18.6 mL/kg. The secondary outcomes of HR, MAP, and ABE showed the most benefit with 24.8 mL/kg of IFE at both 30 and 60 minutes. Conclusions: The greatest benefit to survival occurs with 18.6 mL/kg IFE, while the greatest benefit to HR, MAP, and BE occurs at 24.8 mL/kg IFE. The optimal dose for the treatment of severe verapamil toxicity in this murine model was 18.6 mL/kg.     

Successful extracorporeal life support in a case of severe flecainide intoxication

OBJECTIVE: To show the effectiveness of emergency extracorporeal membrane oxygenation (ECMO) in treating severe, life-threatening flecainide intoxication. DESIGN: Case report. SETTING: Intensive care unit in a quaternary care center. PATIENT: A patient with electromechanical dissociation after severe flecainide acetate overdose. INTERVENTION: ECMO. CASE REPORT: A 30-yr-old male with a history of depression presented after a severe flecainide overdose with plasma concentrations exceeding 20 times the upper boundary of the therapeutic range. At presentation, the patient was in refractory cardiocirculatory collapse and was successfully resuscitated with ECMO. Twenty-six hours later, extracorporeal support could be discontinued and the patient made a full recovery. CONCLUSION: In patients with severe but potentially reversible cardiac dysfunction attributable to flecainide intoxication, ECMO can maintain cardiac output and vital organ perfusion while allowing time for drug redistribution, metabolism, and clearance.     

Survival in a case of life-threatening flecainide overdose

Flecainide acetate is a potent class Ic anti-arrhythmic drug with major sodium channel blocking actions. On the surface electrocardiogram this results in QTc interval prolongation. Overdose with class Ic drugs (< 0.1 % of total intoxications) is uncommon, but management is difficult and the mortality high [1]. Serious flecainide overdose is characterised by ventricular tachyarrhythmias, severe bradycardia and variable degrees of atrioventricular block. This report describes a case of life-threatening flecainide overdose in a previously fit individual, resulting in a combination of cardiac disturbances. The treatment options and management are discussed. Received: 12 December 1997 Accepted: 24 March 1998     

Massive Caffeine Overdose Requiring Vasopressin Infusion and Hemodialysis

Abstract

Introduction.?Massive caffeine overdose is associated with life‐threatening hemodynamic complications that present challenges for clinicians. We describe the highest‐reported serum concentration of caffeine in a patient who survived and discuss the first‐reported use of vasopressin and hemodialysis in a caffeine‐poisoned patient. Case Report.?A 41‐yr‐old woman presented 3 h after ingesting approximately 50 g of caffeine. She subsequently underwent cardiopulmonary resuscitation and received multiple medications in an attempt to raise her blood pressure and control her heart rate without success. Vasopressin infusion increased her blood pressure to the point where hemodialysis could be performed. Despite ensuing multisystem organ failure, she survived and has made a complete recovery. Conclusion.?Hemodialysis and vasopressin infusions may be of benefit in the management of caffeine‐intoxicated patients who fail to respond to standard therapies.     

Intentional overdose with cardiac arrest treated with intravenous fat emulsion and high-dose insulin

Introduction. Nebivolol, a beta blocker with 3–10 times more β₁ cardioselectivity than metoprolol, has caused hypotension and bradycardia in overdose. We report a nebivolol-induced cardiac arrest in the setting of a polydrug ingestion, successfully resuscitated with intravenous fat emulsion (IFE) and high-dose insulin (HDI). Case report. A 48-year-old man was brought to the emergency department after ingesting nebivolol and ethanol, along with possibly diazepam and cocaine. He had a heart rate of 71/min and a blood pressure of 98/61 mmHg. The initial ECG showed sinus rhythm with a QTc of 483 ms and a QRS of 112 ms. Over the subsequent 4 h, he became bradycardic and hypotensive and developed bradyasystolic cardiac arrest. Standard resuscitation including epinephrine had no effect. Spontaneous circulation returned 30 s after a 100 mL bolus of 20% IFE, and the patient then became briefly hypertensive and tachycardic with heart rate and blood pressure measured as high as 123/min and 251/162 mmHg, respectively. His care included IFE infusion along with HDI bolus and infusion with doses as high as 21.8 units/kg/h. With subsequent hypotension, vasopressors were withheld in favor of HDI and supportive care. He was discharged with baseline neurologic function. Discussion. We hypothesize that after the administration of IFE the epinephrine was able to exert its effect on receptors previously occupied with the nebivolol. This would be congruent with the lipid sink theory of IFE mechanism. Conclusion. We report an overdose involving nebivolol in a polydrug ingestion resulting in cardiac arrest, successfully treated with IFE and a very HDI infusion.     

Stevens‐Johnson syndrome: Pathogenesis,diagnosis, and management

Cutaneous drug reactions are the most common type of adverse drug reaction. These reactions, ranging from simple pruritic eruptions to potentially life‐threatening events, are a significant cause of iatrogenic morbidity and mortality. Stevens‐Johnson syndrome (SJS) is a serious and potentially life‐threatening cutaneous drug reaction. Although progress has been made in the management of SJS through early detection, prompt hospitalization, and immediate cessation of offending agents, the prevalence of permanent disabilities associated with SJS remains unchanged. Nevertheless, despite being a problem that is global in scope, government and health care agencies worldwide have yet to find a consensus on either diagnostic criteria or therapy for this disorder. Here, we provide the internist and emergency room physician with a brief review the SJS literature and summarize the latest recommended interventions with the hope of improving early recognition of this disease and prevention of permanent sequelae and mortality that frequently complicate SJS.     

Rhythm control agents and adverse events in patients with atrial fibrillation

Background: Atrial fibrillation (AF) is the commonest rhythm disorder and has major impact on patients. Controversy remains about the best treatment strategy between rate and rhythm control (in addition to adequate thromboprophylaxis). Rhythm control agents are associated with clinically important adverse events. Aim: The aim of this study was to assess the risk of adverse events in patients with AF receiving rhythm control agents. Design of study: This is a retrospective case control note review and outcome linkage analysis. Setting: Setting of this study included patients with a diagnosis of AF receiving amiodarone, flecainide or sotalol in practices registered with the General Practice Research Database (GPRD) in the UK. Method: This is a retrospective case control note review and outcome linkage analysis on the GPRD routine clinical dataset to evaluate the adverse events and predictors of treatment discontinuation in patients using licenced rhythm modifying medication. Results: Adverse events are more common in patients currently or previously taking amiodarone, flecainide or sotalol than age‐ and gender‐matched controls. All three antiarrhythmics were associated with increased all‐cause mortality. Congestive heart failure was more common in all amiodarone and sotalol users as well as past users of flecainide. Thyroid disease was more common in patients treated with amiodarone and sotalol but only amiodarone had an increased risk of pulmonary toxicity. The number of patients with liver failure was too small in all cases for statistical analysis. Conclusion: The rhythm control agents amiodarone, flecainide and sotalol have significant adverse effects which can lead to discontinuation of their use. This should be considered when deciding the most appropriate treatment option for patients with AF.     

Flecainide‐Associated Bradycardia‐Dependent Torsade de Pointes: Another Potential Mechanism of Proarrhythmia

Although flecainide has a risk of proarrhythmia in patients with structural heart disease, its mechanism has been mainly ascribed to use‐dependency and a rapid ventricular response to organized atrial tachyarrhythmias or to ventricular tachycardia. We present a patient who experienced recurrent syncope due to bradycardia‐dependent torsade de pointes (TdP) associated with flecainide‐related bradycardia and QT prolongation. Bradycardia‐dependent TdP with QT prolongation can be considered as one of mechanisms of flecainide‐induced proarrhythmia.     

HIV‐associated pulmonary arterial hypertension: from bedside to the future

Pulmonary arterial hypertension (PAH) is a life‐threatening complication of HIV infection. The prevalence of HIV‐associated PAH (HIV‐PAH) seems not to be changed over time, regardless of the introduction of highly active antiretroviral therapy (HAART). In comparison with the incidence of idiopathic PAH in the general population (1–2 per million), HIV‐infected patients have a 2500‐fold increased risk of developing PAH. HIV‐PAH treatment is similar to that for all PAH conditions and includes lifestyle changes, general treatments and specific treatments.     

American Association of Poison Control Centers

Abstract

120 cases of class IC antiarrhythmic overdose, including propafenone, flecainide, ajmaline and prajmaline overdose, were evaluated with respect to clinical course, therapy and outcome. Whereas drug overdose in general has an overall mortality of less than 1%, intoxication with antiarrhythmic drugs of class IC was associated with a mean mortality of 22.5%. Nausea, which occurred within the first 30 minutes after ingestion, was the earliest symptom. Spontaneous vomiting probably led to self-detoxication in about half the patients. Cardiac symptoms including bradycardia and, less frequently, tachyrhythmia occurred after about 30 minutes to 2 hours. Therapeutic measures included administration of activated charcoal, gastric lavage and a saline laxative, catecholamines, and in some patients, hypertonic sodium bicarbonate, insertion of a transvenous pacemaker and hemoperfusion. Fatal outcome was mainly due to cardiac conduction disturbances progressing to electromechanical dissociation or asystolia. Resuscitation, which had to be performed in 29 patients, was successful in only two of them. No correlation was found between fatal outcome, the type of antiarrhythmic, and ingested dose. Since a specific treatment is not available and resuscitive procedures including sodium bicarbonate and insertion of a pacemaker are of limited therapeutic value, early diagnosis and primary detoxification are most important for prevention of fatal outcome.     

Intravenous fat emulsion to reverse haemodynamic instability from intentional amitriptyline overdose

We report the first case of amitriptyline toxicity treated with intravenous fat emulsion (IFE). Toxicity was manifested as vasopressor-refractory haemodynamic instability despite standard therapy. Our patient recovered with no adverse effects noted.     

The Child With Headache in a Pediatric Emergency Department

Objectives.— To investigate clinical features of a pediatric population presenting with headache to a pediatric emergency department (ED) and to identify headache characteristics which are more likely associated with serious, life‐threatening conditions in distinction from headaches due to more benign processes. Background.— Although headache is a common problem in children visiting a pediatric ED, a few studies thus far have attempted to identify the clinical characteristics most likely associated with suspected life‐threatening disease. Methods.— A retrospective chart review of all consecutive patients who presented with a chief complaint of headache at ED over a 1‐year period was conducted. Etiologies were classified according to the International Headache Society diagnostic criteria 2nd edition. Results.— Four hundred and thirty‐two children (0.8% of the total number of visits) aged from 2 to 18 years (mean age 8.9 years) were enrolled in our study. There were 228 boys (53%) and 204 girls (47%). School‐age group was the most represented (66%). The most common cause of headache was upper respiratory tract infections (19.2%). The remaining majority of non‐life‐threatening headache included migraine (18.5%), posttraumatic headache (5.5%), tension‐type headache (4.6%). Serious life‐threatening intracranial disorders (4.1%) included meningitis (1.6%), acute hydrocephalus (0.9%), tumors (0.7%). We found several clinical clues which demonstrated a statistically significant correlation with dangerous conditions: pre‐school age, recent onset of pain, occipital location, and child's inability to describe the quality of pain and objective neurological signs. Conclusions.— Differential diagnosis between primary and secondary headaches can be very difficult, especially in an ED setting. The majority of headaches are secondary to respiratory infectious diseases and minor head trauma. Our data allowed us to identify clinical features useful to recognize intracranial life‐threatening conditions.     

Efficacy of ivabradine to control ventricular arrhythmias in catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal hereditary disease characterized by complex ventricular arrhythmias provoked by exercise or emotional stress and by a high mortality rate in young individuals. Nadolol alone or in combination with flecainide is the most effective therapy. However, compliance to treatment is often low due to side effects. We report two patients with CPVT in whom side effects of treatment prompted discontinuation of flecainide or nadolol and in whom ivabradine was successfully added to therapy. In these two patients, ivabradine in combination with nadolol or flecainide was well tolerated and successfully suppressed nonsustained polymorphic ventricular tachycardia and couplets. Thus, ivabradine could limit the use of implantable cardioverter‐defibrillators or left cardiac sympathetic denervation in CPVT patients with uncontrollable ventricular arrhythmias.     

Metabolic acidosis and generalized seizures secondary to citalopram overdose: a case report

Selective serotonin re‐uptake inhibitors (SSRIs) are widely used in the community for treating many forms of mental illnesses. Citalopram, a newer generation SSRI, is commonly prescribed, but despite its low toxicity profile has a potential to cause seizures and dysarrythmias in overdose. Data on citalopram overdose‐induced metabolic acidosis are scarce. There have been only three cases of metabolic acidosis reported in the literature due to citalopram overdose in humans and we are reporting the fourth one. We report a case of citalopram overdose with metabolic acidosis and generalized seizure. To our best knowledge, this is the first case reported in Saudi Arabia.     

Bilateral sympathectomy for treatment of refractory ventricular tachycardia

Ventricular tachycardia (VT) commonly occurs in patients with ischemic or nonischemic cardiomyopathy and requires antiarrhythmic drugs, ablation, or advanced circulatory support. However, life‐threatening VT may be refractory to these therapies, and may cause frequent implantable cardioverter defibrillator (ICD) discharges. Left cardiac sympathetic denervation reduces the occurrence of these fatal arrhythmias by inhibiting the sympathetic outflow to the cardiac tissue. We present a 69‐year‐old man with nonischemic cardiomyopathy, life‐threatening VT, and hemodynamic instability with numerous ICD discharges, who remained refractory to antiarrhythmic drug therapy and ablation attempts. He was effectively treated with bilateral cardiac sympathectomy. Six months later, he remained free of VT with no ICD discharges.