Pilsicainide Poisoning: An Autopsy Case and Review of Literature.

We describe an autopsy case of fatal poisoning due to accidental overdose of pilsicainide, which is a Vaughan Williams class IC antiarrhythmic drug (a pure sodium channel blocker). A man in his 50s was found dead in his home at approximately noon. He had ischemic heart disease and insomnia, and had previously demonstrated improper prescription drug adherence. The autopsy revealed old coronary artery bypass grafting and mild fibrosis of myocardium, but no acute myocardial infarction was found in microscopic examination. Toxicological analysis also identified a high blood concentration of pilsicainide (femoral vein blood, 14.9 µg/mL), more than 15 times higher than reported therapeutic levels. The blood concentrations of other drugs were at therapeutic levels, and no alcohol was detected. We concluded that the cause of death was pilsicainide poisoning, based on the results of the autopsy and the toxicological examination. This is the first autopsy report of fatal poisoning due to pilsicainide as a single agent.

Two for One: A Case Report of Intravenous Lipid Emulsion to Treat Local Anesthetic Systemic Toxicity in Term Pregnancy.

Combined spinal-epidural (CSE) analgesia is a frequently used method of labor analgesia. Although it is considered safe and effective, CSE can be complicated by local anesthetic systemic toxicity (LAST), a potentially life-threatening condition. We present a case of LAST that developed in a primigravida 50 minutes after uneventful placement of a CSE. Her symptoms resolved within 10 minutes of administering intralipid emulsion. She subsequently underwent cesarean delivery under spinal anesthesia for failure to progress without sequelae in the mother or infant. LAST in pregnancy can occur at traditionally subthreshold dosing; anesthesiologists must be vigilant to ensure prompt and effective treatment.

Difference of the clinical course and outcome between dapsone-induced methemoglobinemia and other toxic-agent-induced methemoglobinemia.

CONTEXT: Acquired methemoglobinemia is a potentially fatal condition that leads to tissue hypoxia. Although the clinical features of methemoglobinemia depend on the methemoglobin levels, the clinical course would differ depending on the causative agents. OBJECTIVE: We attempted to clarify this issue by comparing the clinical course of methemoglobinemia caused by dapsone and that caused by other toxic agents. MATERIALS AND METHODS: A retrospective case-control study was performed. All patients with methemoglobinemia and who were admitted to the emergency department (ED) of our hospital from 1 January 2002 to 31 December 2014 were included. RESULTS: Of the 34 patients with methemoglobinemia, 15 ingested dapsone (14 with acute overdose and one with chronic therapeutic use) and 19 had been exposed to other toxic agents, such as sodium nitrites, indoxacarb, primaquine, and lidocaine. The clinical characteristics and the course of dapsone-induced and other toxic-agent-induced methemoglobinemia were compared. There was no significant difference in clinical presentation and methemoglobin level (38.5% vs. 35.0%, p = 0.456) upon their ED arrival between the two groups. However, the methemoglobin level after use of methylene blue and the total dose of methylene blue were higher in patients with dapsone-induced methemoglobinemia than in those with other agent-induced methemoglobinemia (11.9% vs. 1.7%, p = 0.001, 455 mg vs. 144 mg, p = 0.006). The majority of dapsone-induced methemoglobinemia (93.3%) required more than 72 h for normalization of the methemoglobin level, despite the use of methylene blue. Five of the study patients died due to multiorgan failure, and all of whom were inpatients with dapsone-induced methemoglobinemia. CONCLUSION: The clinical course of dapsone-induced methemoglobinemia was worse than that of other toxic-agent-induced methemoglobinemia despite no significant difference in their initial clinical presentation. Continuous treatment with serial monitoring of the serum methemoglobin is necessary for patients with dapsone-induced methemoglobinemia.

[Severe local anesthetic intoxication in an infant undergoing circumcision]. / Intoxication grave aux anesthésiques locaux lors d'une circoncision.

Local anesthetic intoxication is an uncommon complication of regional anesthesia. We report the case of a 4-month-old infant who presented with generalized tonic-clonic seizure complicated by cardiac arrest secondary to a severe intoxication to local anesthesia. These complications were observed after a bilateral dorsal penile nerve block with lidocaine for circumcision in a non-hospital setting. This report emphasizes the potential risk of local anesthetic systemic toxicity in such circumstances and describes its treatment.

Status epilepticus, cardiac resuscitation, and posterior reversible encephalopathy syndrome after ingestion of viscous lidocaine: a plea for more childproof packaging of pharmaceuticals.

Ingestion of viscous lidocaine in children can lead to potentially lethal neurologic and cardiac effects. We report the case of a 2-year-old boy who developed posterior reversible encephalopathy syndrome 2 days after unobserved ingestion of about 500 mg viscous lidocaine (40 mg/kg of bodyweight). Initially, the child presented with convulsive status epilepticus and subsequent cardiac arrest necessitating cardiopulmonary resuscitation for eight minutes. After 2 days of full recovery, the child presented with progressive disorientation, dizziness, and visual neglect. Lasting for 2 days, these symptoms finally disappeared completely. Combined with the findings on cerebral magnetic resonance imaging, this episode was interpreted as posterior reversible encephalopathy syndrome. Two weeks after the ingestion, no neurologic and visual abnormalities were found. Viscous lidocaine is prescribed routinely for dentition or other painful lesions in the oral cavity in children. Despite the potential hazardousness of the drug, packaging of viscous lidocaine is not childproof. Therefore, physicians have to instruct the parents carefully to minimize the risk of overuse or accidental ingestion. In general, the use of viscous lidocaine should be limited.

Use of intravenous lipid emulsion to reverse central nervous system toxicity of an iatrogenic local anesthetic overdose in a patient on peritoneal dialysis.

OBJECTIVE: To describe a case of severe central nervous system toxicity after an overdose of lidocaine by local infiltration in a peritoneal dialysis patient and subsequent treatment of the toxicity with lipid emulsion. CASE SUMMARY: A 31-year-old male received an iatrogenic overdose of 1600 mg of lidocaine 2% by infiltration during an attempt to remove and replace a peritoneal dialysis catheter. Within 10 minutes after the last lidocaine injection, the patient exhibited features of local anesthetic toxicity, which included tachycardia, hypertension, shortness of breath, dizziness, and a choking sensation that progressed to hallucinations, dysarthria, and uncoordinated, weak limb movement. Within 10 minutes after administration of a single 1.5-mg/kg intravenous bolus of 1.5 mL/kg [corrected], the patient improved dramatically. After observation overnight in a monitored care setting, the patient was discharged home with no apparent neurologic sequelae. DISCUSSION: Systemic toxicity due to regional anesthesia with local anesthetic agents such as lidocaine has been well described in the medical literature. The use of lipid emulsion as an antidote to the toxicity of local anesthetics and other lipophilic drugs has been suggested as a valuable intervention in both early, rapidly progressive toxicity, as well as toxicity that is refractory to standard treatment. Patients with advanced chronic kidney disease may be more susceptible to systemic effects of lidocaine due to decreased drug elimination. CONCLUSIONS: Central nervous system toxicity due to an overdose of lidocaine was quickly reversed by intravenous lipid emulsion in our patient.

'Ivory wave' toxicity in recreational drug users; integration of clinical and poisons information services to manage legal high poisoning.

BACKGROUND: Novel psychoactive substances or 'legal highs' can be defined as psychoactive substances that have been developed to avoid existing drug control measures. Consistency of name, but with change in the content of the product, may cause harm. This could result in clusters of users being poisoned and developing unexpected physical and psychiatric symptoms. We describe such an event and the clinical phenotypes of a cluster of patients poisoned with a novel psychoactive substance in 'ivory wave' and analyze data from the National Poisons Information Service (NPIS) to estimate use across the United Kingdom. In addition, the likely active ingredient in this cluster of 'ivory wave' poisonings was identified. METHODS: An analysis of consecutive patients attending the Royal Infirmary of Edinburgh emergency department in July and August 2010 with self-reported 'ivory wave' use was performed. Over a similar time frame, poisons enquiries regarding 'ivory wave' to the UK NPIS, by telephone and via the internet-based TOXBASE(®) poisons database ( www.toxbase.org ), were analyzed. A sample of 'ivory wave' powder and biological fluids from poisoned patients were investigated to determine the active ingredient. RESULTS: Thirty four emergency attendances due to 'ivory wave' toxicity were identified. The mean +/- SD (range) age was 28.6 +/- 7.8 (16-44) years. Patients demonstrated a toxidrome which lasted several days, characterized by tachycardia (65%), tachypnoea (76%), dystonia (18%), rhabdomyolysis (96%), leucocytosis (57%), agitation (62%), hallucinations (50%), insomnia (32%) and paranoia (21%). Enquiries to NPIS suggest that 'ivory wave' poisoning occurred throughout the United Kingdom. A sample of 'ivory wave' powder was analyzed and found to contain desoxypipradrol, which was also identified in biological fluids from 4 out of 5 patients tested. DISCUSSION: A cluster of cases presenting after use of a novel psychoactive substance was identified in Edinburgh and desoxypipradrol was identified as the likely cause. It was associated with prolonged psychiatric symptoms as a key feature. This chemical was regulated in response to the wider UK outbreak, which NPIS data suggest was geographically widespread but probably short lived. CONCLUSION: Novel psychoactive substances can produce significant toxicity and data from poisons centres may be used to indirectly detect new 'legal highs' that are causing clinical toxicity.

[Two elderly case reports of renal excretion type drug poisoning caused by dehydration that was due to poor eating in home care].

The elderly patients are susceptible to acute renal failure due to dehydration or infection. Therefore, the drug should be administered with caution. We report two cases of acute renal failure from dehydration that led to a subsequent drug poisoning. Case 1: An 85-year-old woman with a history of colorectal cancer surgery was admitted to our emergency department for appetite loss and weakness. Because she was given a normal amount of drugs under the condition of poor oral intake, she was hospitalized by digitalism. Case 2: A 72-year-old woman was admitted to our emergency department for disturbance of consciousness and appetite loss. The medication given by a staff in geriatric health services facility appeared to have caused a pilsicainide poisoning. As the elderly patients were given a normal amount of drugs under the poor oral intake condition, blood levels of renal excretion type drug had increased in both cases. Medication management for the elderly should be comprehensively considered the background of the individual.

Preliminary results of the Australasian Regional Anaesthesia Collaboration: a prospective audit of more than 7000 peripheral nerve and plexus blocks for neurologic and other complications.

BACKGROUND AND OBJECTIVES: Peripheral nerve blockade is associated with excellent patient outcomes after surgery; however, neurologic and other complications can be devastating for the patient. This article reports the development and preliminary results of a multicenter audit describing the quality and safety of peripheral nerve blockade. METHODS: From January 2006 to May 2008, patients who received peripheral nerve blockade had data relating to efficacy and complications entered into databases. All patients who received nerve blocks performed by all anesthetists during each hospital's contributing period were included. Patients were followed up by phone to detect potential neurologic complications. The timing of follow-up was either at 7 to 10 days or 6 weeks postoperatively, depending on practice location and time period. Late neurologic deficits were defined as a new onset of sensory and/or motor deficit consistent with a nerve/plexus distribution without other identifiable cause, and one of the following: electrophysiologic evidence of nerve damage, new neurologic signs, new onset of neuropathic pain in a nerve distribution area, paresthesia in relevant nerve/plexus distribution area. RESULTS: A total of 6950 patients received 8189 peripheral nerve or plexus blocks. Of the 6950 patients, 6069 patients were successfully followed up. In these 6069 patients, there were a total of 7156 blocks forming the denominator for late neurologic complications. Thirty patients (0.5%) had clinical features requiring referral for neurologic assessment. Three of the 30 patients had a block-related nerve injury, giving an incidence of 0.4 per 1000 blocks (95% confidence interval, 0.08-1.1:1000). The incidence of systemic local anesthetic toxicity was 0.98 per 1000 blocks (95% confidence interval, 0.42-1.9:1000). CONCLUSIONS: These results indicate that the incidence of serious complications after peripheral nerve blockade is uncommon and that the origin of neurologic symptoms/signs in the postoperative period is most likely to be unrelated to nerve blockade.

Medical homicide and extreme negligence.

Deaths that occur during medical care for the treatment of a disease are rarely certified as homicides. Some "medical" deaths, however, have been criminally prosecuted for manslaughter, reckless endangerment, or reckless homicide. We describe 5 deaths due to medical complications that underwent criminal prosecution. Three of the deaths were certified as homicides. Deaths certified as homicides due to the actions (or inactions) of a caregiver occur in 3 circumstances. The first is when the medical caregiver intentionally causes the death of the patient. The second is a death due to treatment by an unlicensed fraud or quack. The final circumstance is due to extreme medical negligence that involves a gross and wanton disregard for the well-being of the patient and is the most controversial in the medical community. The law defines reckless endangerment as the conscious disregard of a known substantial likelihood of injury to the patient. Criminal neglect typically is defined as the failure to provide timely, safe, adequate, and appropriate services, treatment, and/or care to a patient. In instances of extreme medical negligence, a homicide manner of death is appropriate because the fatality is due to the criminal acts (or inactions) of another. It also furthers one of the major goals of the medicolegal death investigation system, which is to safeguard the public health.

Pilsicainide intoxication presenting as left ventricular dyssynchrony in a patient on hemodialysis.

We report here a case of pilsicainide intoxication presenting as left ventricular dyssynchrony in a patient who had been treated on hemodialysis. This is the first report that assessed cardiac function during pilsicainide intoxication by left ventriculography and right heart catheterization.

Are one or two dangerous? Lidocaine and topical anesthetic exposures in children.

Topical anesthetics are found in a variety of prescription and non-prescription preparations, from teething gels to hemorrhoid creams. In 2003, there were 8576 exposures to local/topical anesthetics reported to the American Association of Poison Control Centers, with 67% of cases in the age group younger than 6 years old. This report reviews the available literature involving topical anesthetic exposures in children younger than 6 years old, including the National Library of Medicine's Pub Med database (limited to English language) and data from POISINDEX. Additionally, we reviewed the American Association of Poison Control Centers' annual reports from 1983 to 2003. There were 7 deaths in this age range from topical anesthetics. Although the number of deaths is low, the fact that there have been deaths reveals the serious nature of the toxicity that can result from these readily available non-prescription analgesics. Toxicity may result from topical absorption, ingestion, or aspiration. Additionally, toxicity can result from unintentional as well as therapeutic mishaps. Although the number of cases is limited, these medications can be toxic at low doses-which, in children younger than 6 years of age, may amount to as little as a teaspoon.

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.

[Case of serious lidocaine intoxication].

Lidocaine is frequently used as a local anesthetic and has very low incidence of serious complications. I report on a case of lidocaine intoxication in a 66-year-old man who presented with seizure and cardiac periarrest following the brachial plexus block with 450 mg of lidocaine. Twelve minutes after the lidocaine administration, he became unconscious and 29 minutes after, developed seizure. Bradycardia and subsequent cardiovascular depression were found 74 minutes after the lidocaine block. The patient was successfully treated with diazepam, atropine sulphate and transcutaneous pacing for each symptom, respectively.