Carbon Monoxide Toxicity.

Carbon monoxide accounts for thousands of deaths worldwide each year. Clinical effects can be diverse and include headache, dizziness, nausea, vomiting, syncope, seizures, coma, dysrhythmias, and cardiac ischemia, and severe toxicity generally affects the nervous and cardiovascular systems. Because of its complex pathophysiology, effects of toxicity can be acute or delayed. The diagnosis can be elusive, as carboxyhemoglobin levels do not always correlate with the degree of poisoning. Even when the diagnosis is certain, appropriate therapy is widely debated. Normobaric oxygen is the standard therapy, and the efficacy of hyperbaric oxygen is unclear.

Acute Cytotoxic Cerebellar Edema Subsequent to Fentanyl Patch Intoxication in an Infant.

The opioid epidemic continues to have devastating consequences for children and families across the United States with rising prevalence of opioid use and abuse. Given the ease of access to these medications, accidental ingestion and overdose by children are becoming increasingly more common. The recognition of opioid-induced neurotoxicity and the associated life-threatening complication of acute cerebellar cytotoxic edema are crucial, as are the high morbidity and mortality without timely intervention. We discuss an infant with acute cytotoxic cerebellar edema following mucosal exposure to a transdermal fentanyl patch.

Benzodiazepine-associated atrioventricular block.

Dysrhythmias, although common in overdose situations, are not often seen after benzodiazepine exposures. We report two cases of transient atrioventricular block after benzodiazepine misuse. Case 1 is a 4-year-old boy who was found unresponsive after an ingestion of clonazepam. An electrocardiogram (EKG) performed on emergency department presentation demonstrated first-degree atrioventricular block (PR 206 ms). After flumazenil administration, he developed second-degree atrioventricular block (Mobitz Type 1). EKG abnormalities resolved by morning. Serum clonazepam was 478 ng/mL (laboratory clonazepam reference range, 10-75 ng/mL with a dose of up to 6 mg/day) 5 hours after being found unresponsive. Case 2 is a 23-year-old man who presented to the emergency department after ingesting risperidone, combination hydrocodone/acetaminophen, and alprazolam. On arrival, his EKG demonstrated sinus bradycardia with a PR interval of 182 msec. He subsequently developed second-degree atrioventricular block (Mobitz Type I). Sinus bradycardia with resolution of his atrioventricular block (PR 200 ms) was seen on a third EKG performed 5 hours after presentation. These two patients demonstrated transient first- and second-degree atrioventricular block after benzodiazepine exposure. Benzodiazepines have been shown to alter L-type Ca2+ channel function. This alteration in function may account for the dysrhythmias seen in our patients. Together, these cases serve to remind clinicians of this rare but potentially serious complication associated with benzodiazepine exposure.

The MALAdy of metformin poisoning: Is CVVH the cure?

Inadvertent or intentional metformin overdose can result in death from refractory lactic acidosis. We report a death from metformin-induced refractory lactic acidosis despite aggressive care. A 49-year-old hypertensive diabetic female presented 1 hour after ingesting 60 tablets of 500 mg metformin and 20 combination tablets of 12.5 mg hydrochlorothiazide/20 mg lisinopril. She was awake and alert, with a blood glucose of 579 mg/dL. Chemistry panel revealed lactic acidosis and acute renal failure (arterial blood gas pH, 7.18; pCO(2), 15 mm Hg; pO(2), 127 mm Hg; HCO(3), 6 mmol/L; lactate, 9.6 mmol/L; and creatinine, 1.2 mg/dL [0.8 mg/dL previously]). She received normal saline, sodium bicarbonate, and insulin. On arrival to the intensive care unit she was obtunded, with a blood pressure of 40/25 mm Hg and had worsening acidosis and poor oxygenation (arterial blood gas pH, 6.79; pCO(2), 55; pO(2), 57; HCO(3), 8.4; and base excess of -25 on 100% fractional inspired oxygen). She was intubated and received additional fluid boluses, bicarbonate, and norepinephrine. Continuous veno-venous hemofiltration (CVVH) was started 6 hours after her ingestion. Metformin was 380 microg/mL on CVVH initiation. The patient developed pulseless electrical activity 30 hours after her ingestion, which recurred 20 minutes later. The family requested no further resuscitation. She died 31.5 hours after her ingestion. Metformin concentrations decreased to 97 microg/mL 28 hours after the ingestion on CVVH, with a first-order elimination half-life of 11.3 hours (r(2) = 0.99) and a clearance of 56.2 mL/min. Further investigations on the place of CVVH in the management of the poisoned patient with MALA unable to hemodynamically tolerate conventional hemodialysis may be needed.

Calcium channel blocker toxicity.

Calcium channel blockers continue to be used for the management of a wide variety of adult and pediatric conditions including hypertension, angina pectoris, atrial arrhythmias, Raynaud phenomenon, and migraine headaches. With increased use comes increased potential for misuse and abuse. This article serves as a review of calcium channel blocker physiology with emphasis on presentation and management of the pediatric patient with calcium channel blocker toxicity.

Toxicity associated with carbon monoxide.

Carbon monoxide is an insidious poison that accounts for thousands of deaths each year in North America. Clinical effects maybe diverse and include headache, dizziness, nausea, vomiting,syn-cope, seizures, coma, dysrhythmias, and cardiac ischemia. Children, pregnant women, and patients who have underlying cardiovascular disease are particularly at risk for adverse out-comes. Treatment consists of oxygen therapy, supportive care, and, in selected cases, hyperbaric oxygen therapy.

Brown recluse spider envenomation.

Brown recluse spider bite is a common diagnosis in almost every state in America. In fact, cases have been reported in areas where the spider has never been seen. A review of medical literature reveals that most current concepts regarding brown recluse spider envenomation are based on supposition. In this article, we attempt to review critically our present understanding of brown recluse bites with a focus on the published evidence.

Drug-induced q-T prolongation.

Drug therapy may induce Q-T prolongation by alteration of potassium ion currents in cardiac cells, resulting in abnormal repolarization. Q-T prolongation, whether congenital or acquired, has been associated with the development of the malignant dysrhythmia Torsade de Pointes (TdP), which may result in sudden death. Re-cent regulatory actions and drug withdrawals due to Q-T prolongation or TdP have focused attention on this issue. Although our understanding of the pathophysiology continues to evolve, both patient and medication factors contribute to the individual risk of drug-induced Q-T prolongation or TdP. The clinician should be aware of these issues when prescribing new drugs and should weigh the risks and benefits carefully when prescribing drugs known to prolong the Q-T interval.

Carbon monoxide poisoning.

CO is an ubiquitous poison with many sources of exposure. CO poisoning produces diverse signs and symptoms that are often subtle and may be easily misdiagnosed. Failure to diagnose CO poisoning may result insignificant morbidity and mortality and permit continued exposure to a dangerous environment. Treatment of CO poisoning begins with inhalation of supplemental oxygen and aggressive supportive care. HBOT accelerates dissociation of CO from hemoglobin and may also prevent DNS. Absolute indications forHBOT for CO poisoning remain controversial, although most authors would agree that HBOT is indicated in patients who are comatose or neurologically abnormal, have a history of LOC with their exposure, or have cardiac dysfunction. Pregnancy with an elevated CO-Hgb level(>15%-20%) is also widely, considered an indication for treatment.HBOT may be considered in patients who have persistent symptoms despite NBO, metabolic acidosis, abnormalities on neuropsychometric testing, or significantly elevated levels. The ideal regimen of oxygen therapy has yet to be determined, and significant controversy exists regarding HBOTtreatment protocols. Often the local medical toxicologist, poison control center, or hyperbaric unit may assist the treating physician with decisions regarding therapy.

Carbon monoxide poisoning.

CO is an insidious poison with many sources of exposure. CO poisoning produces diverse signs and symptoms, which often are subtle and can be misdiagnosed easily. Failure to diagnose CO poisoning may result insignificant morbidity and mortality and allow continued exposure to a dangerous environment. In the ED, a high index of suspicion must be maintained for occult CO exposure. Headache, particularly when associated with certain environments, and flulike illness in the wintertime with symptomatic cohabitants should raise the index of suspicion in the ED significantly for occult CO poisoning. Emergency treatment of CO poisoning begins with inhalation of supplemental oxygen and aggressive supportive care. HBOT accelerates dissociation of CO from hemoglobin and may prevent DNS. Absolute indications for HBOT for CO poisoning remain controversial, although most would agree that HBOT is indicated in patients who are comatose, are neurologically abnormal, have a history of loss of consciousness with their exposure, or have cardiac dysfunction. Pregnancy with an elevated CO-Hgb level (>15-20%) also is widely considered an indication for treatment. HBOT may be considered in patients who have persistent symptoms despite NBO, metabolic acidosis, abnormalities on neuropsychometric testing, or significantly elevated levels. The ideal regimen of oxygen therapy has yet to be determined, and significant controversy exists regarding HBOT protocols. The emergency physician may be confronted with the difficult decision regarding disposition and even transfer to a hyperbaric facility. Often the local medical toxicologist, poison control center, or hyperbaric unit can assist the emergency physician with the decision-making process.

What is the rate of adverse events after oral N-acetylcysteine administered by the intravenous route to patients with suspected acetaminophen poisoning?

STUDY OBJECTIVE: We conduct a study to determine the rate of adverse events (anaphylactoid and cardiorespiratory) associated with the use of oral N-acetylcysteine by the intravenous route for the treatment of suspected acetaminophen poisoning and to examine specific variables that may be associated with adverse events. METHODS: We conducted a retrospective medical record review with explicit criteria. All patients who received oral N-acetylcysteine by the intravenous route from September 1995 to September 2001 were included. Patients were identified by cross-matching 3 databases. Adverse events were divided into categories of cutaneous, systemic, or life threatening. Five reviewers abstracted charts by using a standardized data collection form. Interrater reliability was calculated by using 24 medical records abstracted by all 5 reviewers. RESULTS: There were 7 adverse events identified in 187 patients (3.7%; 95% confidence interval 1.0% to 6.5%). Six adverse events were cutaneous and responded rapidly to antihistamines. One adverse event was life threatening but not clearly related to N-acetylcysteine. A high rate of antihistamine exposure (53%) was identified before the administration of N-acetylcysteine. Interrater agreement was higher than 95%. CONCLUSION: Intravenous administration of an oral solution of N-acetylcysteine is associated with a low rate of adverse events and should be considered for selected patients with suspected acetaminophen poisoning.

Dimercaptosuccinic acid and Prussian Blue in the treatment of acute thallium poisoning in rats.

INTRODUCTION: Despite being banned as a pesticide, thallium still results in human and animal poisonings. Current recommended treatments include the use of the chemical Prussian Blue. Limitations in its availability may result in Prussian Blue not being obtainable in the thallium-poisoned patient. The chelator 2,3-Dimercaptosuccinic acid (DMSA) is currently FDA-approved for use in childhood lead poisoning and has been reported to be beneficial in treating other heavy metal poisonings. The objective of this study was to determine the efficacy of DMSA as a treatment for thallium poisoning by studying mortality and whole-brain concentrations in thallium poisoned rats. MATERIAL AND METHODS: Rats were gavaged with 30 mg/kg of thallium. After 24 hours they were randomized to DMSA (n = 20) 50 mg/kg twice daily for 5 days, Prussian Blue (n = 20) 50 mg/kg twice daily for 5 days, or control (n = 30). Animals were monitored twice daily for weight loss and mortality. Animals losing greater than 20% of their starting weight were euthanized and counted as a mortality. All surviving rats at 120 hours had their brains harvested and digested and underwent subsequent thallium analysis. RESULTS: The rate of survival in DMSA-treated animals compared to control was 45% vs. 21%, p = 0.07. Mean whole-brain thallium concentrations between DMSA and control rats were 3.4 vs. 3.0 microg/g, p = 0.06. Prussian Blue-treated rats had significantly improved survival (70% vs. 21%, p < 0.01) and lower whole-brain thallium concentrations (1.6 vs. 3.0 microg/g, p < 0.01 tissue) compared to controls. CONCLUSION: DMSA failed to reduce brain thallium concentrations in rats poisoned with thallium and had an indeterminate effect on mortality while Prussian Blue significantly reduces both brain thallium concentrations and mortality.

Intrathecal baclofen withdrawal mimicking sepsis.

Baclofen (Lioresal) is a drug of choice to treat spasticity and is increasingly being administered intrathecally via an implantable pump in cases refractory to oral therapy. Emergency physicians will likely treat patients with baclofen withdrawal or overdose as this treatment becomes more widespread. The syndrome of baclofen withdrawal presents with altered mental status, fever, tachycardia, hypertension or hypotension, seizures, and rebound spasticity, and may be fatal if not treated appropriately. Baclofen withdrawal may mimic other diseases including sepsis, meningitis, autonomic dysreflexia, malignant hyperthermia, or neuroleptic malignant syndrome. Treatment consists of supportive care, reinstitution of baclofen, benzodiazepines, and diagnosis and eventual repair of intrathecal pump and catheter malfunction.

Droperidol, QT prolongation, and sudden death: what is the evidence?

STUDY OBJECTIVE: Droperidol is a butyrophenone commonly used as an antiemetic and antipsychotic in the United States since US Food and Drug Administration (FDA) approval in 1970. Its labeling has recently been revised, with a black box warning for cases of QT prolongation leading to torsades de pointes and death. A black box warning is applied when serious adverse drug reactions are uncovered for medications. We sought to examine the evidence of a causal association suggested by the black box warning to aid clinicians in their risk-benefit analyses regarding further use of droperidol. METHODS: A literature search was undertaken to determine the evidence regarding the association between droperidol and QT prolongation or torsades de pointes. The evidence was then evaluated by using evidence-based medicine principles. In addition, a review of the FDA regulatory process is presented. RESULTS: Three clinical studies, 1 published abstract, and 7 case reports were reviewed. Available postmarketing surveillance data (MedWatch reports) were also reviewed. Applying the criteria of evidence-based medicine and Hill's criteria, the evidence is not convincing for a causal relationship between therapeutic droperidol administration and life-threatening cardiac events. CONCLUSION: The recent black box warning appears to have originated from postmarketing surveillance data rather than data reported in the peer-reviewed medical literature. Ongoing monitoring of drug safety and more definitive study appear appropriate.

Hyperbaric oxygen therapy in acute ischemic stroke: results of the Hyperbaric Oxygen in Acute Ischemic Stroke Trial Pilot Study.

BACKGROUND AND PURPOSE: Hyperbaric oxygen therapy (HBO) has promise as a treatment for acute stroke. This study was conducted to evaluate the efficacy, safety, and feasibility of using HBO in acute ischemic stroke. METHODS: We conducted a randomized, prospective, double-blind, sham-controlled pilot study of 33 patients presenting with acute ischemic stroke who did not receive thrombolytics over a 24-month period. Patients were randomized to treatment for 60 minutes in a monoplace hyperbaric chamber pressurized with 100% O2 to 2.5-atm absolute (ATA) in the HBO group or 1.14 ATA in the sham group. Primary outcomes measured included percentage of patients with improvement at 24 hours (National Institutes of Health Stroke Scale [NIHSS]) and 90 days (NIHSS, Barthel Index, modified Rankin Scale, Glasgow Outcome Scale). Secondary measurements included complications of treatment and mortality at 90 days. RESULTS: Baseline demographics were similar in both groups. There were no differences between the groups at 24 hours (P=0.44). At 3 months, however, a larger percentage of the sham patients had a good outcome defined by their stroke scores compared with the HBO group (NIHSS, 80% versus 31.3%; P=0.04; Barthel Index, 81.8% versus 50%; P=0.12; modified Rankin Scale, 81.8% versus 31.3%; P=0.02; Glasgow Outcome Scale, 90.9% versus 37.5%; P=0.01) with loss of statistical significance in a intent-to-treat analysis. CONCLUSIONS: Although our HBO protocol appears feasible and safe, it does not appear to be beneficial and may be harmful in patients with acute ischemic stroke.