The X factor: Lack of bleeding after an acute apixaban overdose

We present an acute apixaban overdose without reported coingestants; it is the first such case report associated with multiple serum drug levels to assist in determining overdose kinetics. A 62 year old female presented to an emergency department (ED) 2 hours after ingesting sixty 5 mg tablets (5mg/kg) of her spouse's apixaban medication. She denied coingestants, and did not take her prescribed medications that day. Her vital signs were normal and she denied symptoms. Chemistry and hematology labs were unremarkable. Plasma apixaban concentrations were 2765.6 ng/ml at 14 hours post ingestion with a non-linear half life. There was no utilization of blood products or factor replacement. There was never any bleeding, and her hemoglobin did not decrease. This case demonstrates that a single ingestion of apixaban can occur without any complications occurring.     

The spectrum of acute heart failure after venlafaxine overdose

Abstract

Objective. Venlafaxine is a bicyclic antidepressant that may be associated with severe cardiotoxicity following large overdose. The purpose of this short case series is to present different patterns of venlafaxine-related cardiotoxicity and to discuss the potential mechanisms. Case series. Between January 2010 and July 2011, four patients were admitted to an ICU with acute left ventricular failure following large venlafaxine overdoses. The age of the four female patients ranged from 35 to 65 years. None of them had no history of cardiovascular disease. The amount of venlafaxine ingested by history ranged from 3150 to 13500 mg (extended-release preparation in two cases). The peak serum venlafaxine concentration was between 2153.3 and 9950 ng/ml. Three patients died and one recovered rapidly. The initial ECG revealed only mild abnormalities in two cases. In two patients, at least one ECG recording demonstrated a widening of QRS interval. In three patients, echocardiography disclosed a left ejection fraction of 15%–18%. Two patients presented a severe serotonin syndrome, with major rhabdomyolysis. Seizures were noted in two cases, including one patient with status epilepticus. Three patients were mechanically ventilated. The causes of death were refractory hypoxemia, malignant arrhythmias, and cardiogenic shock, respectively. Discussion. Severe and diffuse left ventricular dysfunction may be observed after large venlafaxine overdoses and this is not always associated with severe cardiac conduction function abnormalities. The mechanisms underlying venlafaxine-related cardiac failure with preserved normal cardiac conduction are discussed. A possible explanation may be a catecholamine-induced myocardial damage in relationship with the inhibition of norepinephrine (and dopamine) reuptake.     

Theophylline overdose: acute single ingestion versus chronic repeated overmedication

Currently available guidelines for managing theophylline intoxication do not distinguish between acute single ingestion and chronic repeated overmedication and do not reliably predict which patients should undergo hemoperfusion. Although hemoperfusion is widely recommended when serum concentrations exceed 40-60 mg/l, many patients with acute overdose tolerate much higher levels without serious toxicity. Because manifestations of toxicity might be dependent on the chronicity of the overdose, the authors retrospectively compared the clinical features of 15 patients with chronic repeated overmedication with those of 27 patients suffering acute single overdose. Patients suffering chronic repeated overmedication developed seizures (7/15) and serious arrhythmias (4/15) with serum levels of 28-70 mg/l. By contrast, only one of 19 patients suffering acute single overdose with peak levels less than 100 mg/l had seizures, and only two of 19 with levels less than 100 mg/l had serious arrhythmias. However, of the eight single-overdose patients with levels over 100 mg/l, seven had seizures and three had serious arrhythmias. Single-overdose patients were easily recognized by the presence of hypotension, hypokalemia, and low serum bicarbonate, features not present in chronic-type patients. Thus, while patients with theophylline overdose caused by chronic repeated overmedication frequently develop seizures and arrhythmias with serum levels of 40-70 mg/l, those with acute single ingestion are highly unlikely to suffer serious complications unless serum levels exceed 100 mg/l. Management of the intoxication, especially selection of patients for hemoperfusion, should be based on whether the overdose is caused by an acute single ingestion or chronic repeated overmedication.     

Identifying risks and responding to overdose: piloting of an overdose prevention programme

This paper reports the development and piloting of an Overdose Prevention Programme (OPP) targeted at educating drug users themselves and based on a multi-agency approach utilizing the expertise of specialist agencies and services. In the initial phase of the study, indepth, semi-structured interviews were carried out with a small number of drug users to determine commonly recurring themes and to identify myths and gaps in drug users' knowledge in respect of overdose. From information gathered, an overdose prevention questionnaire (OPQ) was designed and a survey carried out with 111 participants to gather data to determine the incidence of overdose and the accuracy of users' knowledge regarding overdose. A five-session OPP was subsequently designed to educate drug users about overdose (including risks, recognition and response) and to teach them how to pass on information to other drug users as peer educators. At completion of the pilot phase of this study, 28 drug users had enrolled for the programme, with 22 participants completing all five sessions. Initial evaluation indicates that users completing the programme significantly increased their level of knowledge relating to recognition of overdose and their ability to respond appropriately when faced with an overdose situation.     

Lack of significant bleeding despite large acute rivaroxaban overdose confirmed with whole blood concentrations

Background: Since intentional overdose with rivaroxaban is expected to lead to significant coagulopathy and bleeding, prophylactic reversal has been suggested. We report a single massive ingestion confirmed by a blood concentration that was managed with expectant therapy alone.

Case report: A 71-year-old man with atrial fibrillation, aortic valve replacement, and congestive heart failure presented to the emergency department after an intentional ingestion of 97 (1940?mg total) rivaroxaban tablets in a suicide attempt. Initial laboratories revealed: PT, 60.2?s; INR 7.2; aPTT, 55.7?s; BUN 28?mg/dL; and creatinine 1.2?mg/dL. A whole-blood rivaroxaban concentration obtained on hospital-day three was 160?ng/mL. The patient was admitted for continued observation and the coagulation markers trended downward with no major bleeding events. No reversal agents or blood products were given during his hospitalization.

Conclusion: In the setting of a single, acute rivaroxaban overdose, with normal renal function, and no active bleeding, conservative therapy alone may be sufficient.     

Anti-Xa activity in apixaban overdose: a case report

Introduction: Apixaban is a novel oral anticoagulation agent that exerts its effect through direct factor Xa inhibition. We present a case of multi-drug overdose including apixaban with associated apixaban concentrations.

Case: A 53 year-old man presented to our metropolitan hospital following a deliberate self-poisoning with 200?mg apixaban, 35?mg ramipril, 105?mg bisoprolol, 280?mg atorvastatin, 6?mg colchicine, 37.4?mg magnesium, 4?×?500?mg paracetamol/9.5?mg codeine/5?mg phenylephrine and alcohol. He developed hypotension that was treated with noradrenaline. His initial and peak apixaban concentration was 1022.6?ng/ml and was associated with only minor bleeding from his femoral central line insertion site, which improved with local compression. Vitamin K 10?mg (at 9?h post-ingestion) and Prothrombinex-VF 2000 units (at 13?h post-ingestion) were also administered without any observed effect on coagulation studies. Apixaban elimination appeared to display first-order kinetics with an elimination half-life of 7.4?h. His plasma apixaban concentration was within the therapeutic dose range 10?h post-ingestion and he recovered uneventfully.

Conclusion: A case of apixaban overdose with associated apixaban concentrations is presented. There was rapid resolution of anticoagulation with no demonstrable benefit of currently available clotting factor replacement.     

Successful treatment of severe bleeding with recombinant factor VIIa after kidney transplantation

Recombinant factor VIIa (rFVIIa, NovoSeven) has been registered for the treatment of bleeding episodes in patients with inherited or acquired hemophilia A or B with inhibitors. Furthermore, rFVIIa has been used successfully for the treatment of bleeding in patients with thrombocytopenia, and acquired and congenital platelet dysfunction. The definite spectrum of indications for rFVIIa has not yet been established. We describe a case of severe intra-abdominal bleeding 3 days after non-heart beating kidney transplantation in a patient with severe coronary artery disease in which rFVIIa (a single intravenous bolus injection 70 g/kg bodyweight) was successfully used. No thrombotic complications occurred. This report demonstrates that rFVIIa might be safe and effective after recent renal transplantation.     

Electrocardiographic effects of methylphenidate overdose

Objectives.?Stimulants used in the management of attention-deficit hyperactivity disorder have been associated with an increased risk of sudden cardiac death. One mechanism could involve drug-induced repolarization delay, reflected as prolongation of the QT interval on the electrocardiogram, which has been described in some recipients of methylphenidate in therapeutic doses. Because QT prolongation is usually dose-related, this study was performed to investigate effects of methylphenidate overdose on the QT interval.?Methods.?Adults with methylphenidate overdose identified retrospectively were matched for sex and heart rate with a control subject with overdose of a noncardiotoxic substance, mainly acetaminophen. Notes were reviewed for clinical details and coingestants. Admission 12-lead electrocardiograms were individually calibrated and analyzed using a manual digitizer in a blinded manner by a single investigator. Mean QRS and QT intervals were calculated and differences between groups were analyzed.?Results.?Twenty-three cases of methylphenidate overdose (median reported dose 120 mg, range 40–1,500 mg) were identified (10 males, 13 females, mean age 27.8 years). There were multiple coingestants. Level of consciousness and mean hemodynamic variables were within normal limits for all cases. Symptoms recorded in cases included anxiety (32%), dilated pupils (20%), abdominal pain (16%), vomiting (12%), palpitations (12%), and chest pain (8%). No arrhythmias were recorded. Mean heart rate was 92.4/min in methylphenidate cases and 93.8/min in the heart rate-matched controls. There were no significant differences between the groups in mean QRS (cases 86.1, controls 86.2, mean difference 0.1, 95% confidence interval = ?5.1 to 5.0 ms) or mean QT intervals (cases 354, controls 355, mean difference ?0.8, 95% confidence interval = ?10.7 to 9.2 ms).?Conclusions.?Methylphenidate overdose is unlikely to have substantial effects on the QRS or QT intervals.     

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     

Application of pharmacokinetic-pharmacodynamic modelling in management of QT abnormalities after citalopram overdose

Objective

To develop guidelines for the management of QT prolongation after citalopram overdose, including decontamination with single-dose activated charcoal (SDAC) and cardiac monitoring.

Design

Simulation study using a previously developed pharmacokinetic-pharmacodynamic (PKPD) model which predicted the time-course of QT prolongation and the effect of citalopram dose and use of SDAC on QT prolongation.

Main measures and results

The previously developed PKPD model was used to address the following in patients following citalopram overdose: (1) Above what dose should patients be decontaminated? (2) Above what dose should patients have cardiac monitoring? (3) For what period of time should patients be monitored? The primary outcome was QT,RR combinations above an abnormal threshold as a surrogate predictor of torsades de pointes. Simulations were performed using MATLAB for an overdose patient with typical demographics: 30-year-old female with a heart rate of 79?bpm taking citalopram therapeutically. The simulations showed: (1) There was significant benefit associated with the administration of SDAC to patients following citalopram overdose ingesting >?600?mg; (2) With citalopram overdoses >?1,000?mg it was advisable to give SDAC and cardiac monitor the patient; (3) The risk of developing future abnormal QT,RR combinations was less than 1% in patients with normal QT,RR combinations up to 13?h post-dose, so the minimum monitoring time for citalopram overdoses >?1,000?mg should be 13?h. Recommended dose levels for intervention should be lowered in older patients and patients with tachycardia, while men are less sensitive to QT prolongation.

Conclusions

Guidelines for the management of QT prolongation after citalopram overdose were developed. We believe the model will help clinicians to decide which patients to decontaminate and monitor.     

Angiography findings and endovascular management of acute nonvariceal gastrointestinal bleeding: A pictorial essay

Patients with acute nonvariceal gastrointestinal bleeding (GIB) not treatable via endoscopic therapy require angiography and endovascular management. If the source of the bleeding can be identified on angiography, the bleeding can be controlled with minimal complications by endovascular treatments such as intra-arterial infusion of vasopressin, embolization, covered stent placement, or a combination thereof. This pictorial essay reviews the angiographic findings for and the endovascular management of acute nonvariceal GIB.     

Early postoperative bleeding after living donor liver transplantation

We discuss the clinical impacts of early postoperative bleedings after LDLT and CT findings or CT angiographic findings compared with angiography according to the various bleeding causes. Sudden development of hematoma as well as extravasation of contrast material on CT scan are thought to be predictive CT findings of early postoperative bleeding in post-hepatic transplant patients. Careful consideration for these findings can prevent the progression into a catastrophic status that requires surgical management.     

Position paper update: Whole bowel irrigation for gastrointestinal decontamination of overdose patients

Abstract

Context. A position paper on the use of whole bowel irrigation (WBI) was first published in 1997 by the American Academy of Clinical Toxicology (AACT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) and updated in 2004. The aims of this paper are to briefly summarize the content of the 2004 Position Paper and to present any new data and recommendations. Methods. A systematic review of the literature from January 2003 to February 28, 2013 was conducted using multiple online databases for articles concerning WBI for gastrointestinal decontamination. An evidence table was created for applicable articles. The authors produced the initial draft that was reviewed by AACT and EAPCCT. Results. The literature search produced 60 articles with the possibility of applicable human data. Based mainly on volunteer studies, WBI can be considered for potentially toxic ingestions of sustained-release or enteric-coated drugs particularly for those patients presenting later than 2 h after drug ingestion when activated charcoal is less effective. WBI can be considered for patients who have ingested substantial amounts of iron, lithium, or potassium as the morbidity is high and there is a lack of other potentially effective options for gastrointestinal decontamination. WBI can be considered for removal of ingested packets of illicit drugs in “body packers.” However, controlled data documenting improvement in clinical outcome after WBI are lacking. WBI is contraindicated in patients with bowel obstruction, perforation, or ileus, and in patients with hemodynamic instability or compromised unprotected airways. WBI should be used cautiously in debilitated patients and in patients with medical conditions that might be further compromised by its use. The concurrent administration of activated charcoal and WBI might decrease the effectiveness of the charcoal. The clinical relevance of this interaction is uncertain. Conclusion. WBI can facilitate removal of select toxicants from the gastrointestinal tract in some patients, but there is no convincing evidence from clinical studies that it improves the outcome of poisoned patients. There is no new evidence that would require a major revision of the conclusions of the 2004 position statement.     

Isoniazid overdose: Four case reports and review of the literature

Objectives To review the pathophysiology, presentation and treatment of isoniazid (INH) intoxication.Data sources Human, animal and modeling studies published since 1940 identified through MEDLINE and a review of the bibliographies of relevant articles.Study selection and data extraction The studies identified were reviewed with emphasis on the most recent. Earlier studies were selected for their historical value and relevance to the clinical setting.Data synthesis Isoniazid overdose is a potentially fatal intoxication. The incidence of tuberculosis has recently increased in the United States and therefore the frequency of INH overdose may also increase. Patients with INH overdose may present with nausea, vomiting, ataxia, symptoms reminiscent of atropine intoxication, coma and grand mal seizures. Lactic acidosis is revealed by laboratory evaluation. Treatment requires admission to the ICU for ventilatory support, and management of seizures and acidbase abnormalities. Pyridoxine, in a dose equivalent to the amount of INH ingested is the only effective antidote.Conclusions INH overdose should be suspected in any patient presenting with seizures and metabolic acidosis. Prognosis is good when treatment is instituted early.     

Severe bleeding after operation of preauricular fistula: A case report

BACKGROUNDSevere eyelid edema and blood accumulation in the submandibular space after preauricular fistula surgery is rarely reported.CASE SUMMARYWe report a 4-year-old girl with eyelid edema and swelling of the submandibular region after preauricular fistula resection under general anesthesia. When drug treatment failed, neck computed tomography examination was performed, which confirmed severe bleeding in the submandibular space. Later, exploration and ligation of the superficial temporal artery were performed under general anesthesia to stop the bleeding. The child was successfully treated, and there were no abnormalities over 1 year of follow-up.CONCLUSIONWhen severe bleeding occurs after preauricular fistula surgery, superficial temporal artery rupture should be considered as a cause.