Treatment of Toxin-Related Status Epilepticus With Levetiracetam, Fosphenytoin, or Valproate in Patients Enrolled in the Established Status Epilepticus Treatment Trial.

STUDY OBJECTIVE: We describe a subset of patients with toxin-related precipitants of seizures/status epilepticus enrolled in the Established Status Epilepticus Treatment Trial (ESETT). METHODS: The ESETT was a prospective, double-blinded, adaptive trial evaluating levetiracetam, valproate, and fosphenytoin as second-line agents in benzodiazepine-refractory status epilepticus in adults and children. The primary outcome was the absence of seizures and improvement in the level of consciousness 1 hour after study drug administration. In this post hoc analysis, the safety and efficacy of second-line agents in a subset of patients with toxin-related seizures are described. RESULTS: A total of 249 adults and 229 children were enrolled in the ESETT. Toxin-related seizures occurred in 29 (11.6%) adults and 1 child (0.4%). In adults, men were more likely to have toxin-related seizures than women (25 of 145, 17.2% versus 4 of 104, 3.9%). The most common toxin-related precipitants were alcohol withdrawal and cocaine, 11(37%) of 30 patients each. Cocaine was used with other substances by most patients 10 (91%) of 11, most commonly with an opioid 7 (64%) of 11. For alcohol withdrawal-related seizures, treatment successes with levetiracetam, valproate, and fosphenytoin were 3 (100%) of 3, 3 (50%) of 6, and 1 (50%) of 2, respectively. For cocaine-related seizures, treatment success was 1 (14%) of 7 for levetiracetam, 0 (0%) of 1 for valproate, and 1 (33%) of 3 for fosphenytoin. One patient who used cocaine and an opioid received fosphenytoin and developed life-threatening hypotension. CONCLUSION: In the ESETT, approximately 1 in 10 adult patients with status epilepticus presented with a toxin-related seizure. Alcohol withdrawal and cocaine/opioid use were the most common toxin-related precipitants. Toxin-related benzodiazepine-refractory status epilepticus was successfully treated with a single dose of second-line antiseizure medication in 42% of the patients.

Amanita phalloides Mushroom Poisonings - Northern California, December 2016.

Amanita phalloides, colloquially known as the "death cap," belongs to the Phalloideae section of the Amanita family of mushrooms and is responsible for most deaths following ingestion of foraged mushrooms worldwide (1). On November 28, 2016, members of the Bay Area Mycological Society notified personnel at the California Poison Control System (CPCS) of an unusually large A. phalloides bloom in the greater San Francisco Bay Area, coincident with the abundant rainfall and recent warm weather. Five days later, CPCS received notification of the first human A. phalloides poisoning of the season. Over the following 2 weeks, CPCS was notified of an additional 13 cases of hepatotoxicity resulting from A. phalloides ingestion. In the past few years before this outbreak, CPCS received reports of only a few mushroom poisoning cases per year. A summary of 14 reported cases is presented here. Data extracted from patient medical charts revealed a pattern of delayed gastrointestinal manifestations of intoxication leading to dehydration and hepatotoxicity. Three patients received liver transplants and all but one recovered completely. The morbidity and potential lethality associated with A. phalloides ingestion are serious public health concerns and warrant medical provider education and dissemination of information cautioning against consuming foraged wild mushrooms.

Unintentional Pediatric Cocaine Exposures Result in Worse Outcomes than Other Unintentional Pediatric Poisonings.

BACKGROUND: Unintentional pediatric cocaine exposures are rare but concerning due to potentially serious complications such as seizures, dysrhythmias, and death. OBJECTIVES: The objectives were to assess the demographic and clinical characteristics of pediatric cocaine exposures reported to the California Poison Control System. METHODS: This is a retrospective study of all confirmed pediatric (< 6 years of age) cocaine exposures reported to the California Poison Control System from January 1, 1997-September 30, 2010. Case narratives were reviewed for patient demographics, exposure details, clinical effects, therapy, hospitalization, and final outcome. RESULTS: Of the 86 reported pediatric cocaine exposures, 36 had positive urine drug testing and were included in the study cohort. The median age at presentation was 18 months (range: 0-48 months), and 56% were male (n = 20). The most common clinical manifestations were tachycardia and seizures. The most common disposition was admission to an intensive care unit (n = 14; 39%). Eleven cases (31%) were classified as having a major effect as per American Association of Poison Control Centers case coding guidelines. One child presented in asystole with return of spontaneous circulation after cardiopulmonary resuscitation and multiple vasoactive medications. The proportion of cocaine exposures with serious (moderate or major) outcomes (66.7%; 95% confidence interval 50.3-79.8%) was higher than other pediatric poisonings reported to the American Association of Poison Control Centers during the study period (0.88%; 95% confidence interval 0.87-0.88). CONCLUSIONS: Although pediatric cocaine exposures are rare, they result in more severe outcomes than most unintentional pediatric poisonings. Practitioners need to be aware of the risk of recurrent seizures and cardiovascular collapse associated with cocaine poisoning.

Treatment of drug-induced seizures.

Seizures are a common complication of drug intoxication, and up to 9% of status epilepticus cases are caused by a drug or poison. While the specific drugs associated with drug-induced seizures may vary by geography and change over time, common reported causes include antidepressants, stimulants and antihistamines. Seizures occur generally as a result of inadequate inhibitory influences (e.g., gamma aminobutyric acid, GABA) or excessive excitatory stimulation (e.g. glutamate) although many other neurotransmitters play a role. Most drug-induced seizures are self-limited. However, status epilepticus occurs in up to 10% of cases. Prolonged or recurrent seizures can lead to serious complications and require vigorous supportive care and anticonvulsant drugs. Benzodiazepines are generally accepted as the first line anticonvulsant therapy for drug-induced seizures. If benzodiazepines fail to halt seizures promptly, second line drugs include barbiturates and propofol. If isoniazid poisoning is a possibility, pyridoxine is given. Continuous infusion of one or more anticonvulsants may be required in refractory status epilepticus. There is no role for phenytoin in the treatment of drug-induced seizures. The potential role of ketamine and levetiracetam is promising but not established.

Predictors of Death and Prolonged Renal Insufficiency in Ethylene Glycol Poisoning.

BACKGROUND: We assessed the predictive value of selected factors on the outcomes of death and prolonged renal insufficiency (RI) from ethylene glycol poisoning. METHODS: Retrospective, observational California Poison Control System study, over a 10-year period (1999-2008). We compared 2 groups. The first group (D/RI) included 59 patients who died (9 patients) or had prolonged RI (50 patients). Prolonged RI was defined as kidney injury in which dialysis was required for greater than 3 days after presentation. The second group (RECOV) of 62 patients had an uncomplicated recovery. Secondarily, we evaluated the association of time to antidote (ethanol and/or fomepizole) and time to dialysis with these outcomes. RESULTS: The D/RI group was more likely than the RECOV group to present comatose, have seizures, and require intubation. The D/RI group had a lower mean initial arterial pH of 7.03 (standard deviation [SD] 0.20), compared to 7.27 (SD 0.14) for the RECOV group. The D/RI group had a higher initial creatinine (1.7 mg/dL, SD 0.71) than that of the RECOV group (1.0 mg/dL, SD 0.33). Patients with a time to antidote greater than 6 hours had a higher odds of dying or having prolonged RI (OR 3.34, 95% CI : 1.21-9.26) Patients with a time to dialysis greater than 6 hours had a lower odds of dying or having prolonged RI (OR 0.36, 95% CI : 0.15-0.87). CONCLUSION: Compared to survivors with an uncomplicated recovery, patients poisoned with ethylene glycol who died or had prolonged RI were more likely to exhibit clinical signs such as coma, seizures, and acidosis. Antidote administration within 6 hours is associated with better outcomes, unlike earlier time to dialysis.

Multiple MDMA (Ecstasy) overdoses at a rave event: a case series.

Twelve patients with 3,4-methylenedioxymethamphetamine (MDMA) toxicity from a single rave event presented to multiple San Francisco Bay area hospitals with various life-threatening complications including seizures and hyperthermia. Eight required emergent endotracheal intubation and six had hypotension. Hyperkalemia, acute kidney injury, and rhabdomyolysis were present in most of the patients. In all, 2 patients died, 4 survived with permanent neurologic, musculoskeletal, and/or renal sequelae, and 6 survived without any apparent lasting deficits. Hyperthermia was present in 10 patients and was severe (40.9-43° C) in 7. Using multiple cooling methods, the average time to achieve cooling was 2.7 hours. Serum drug analysis was performed on 3 patients, demonstrating toxic MDMA concentrations without the presence of other xenobiotics. Two capsules confiscated by police at the event contained 82% and 98% MDMA, respectively, without other pharmacologically active compounds. Capsule #2 contained 270 mg MDMA, which is more than twice the amount of MDMA usually contained in 1 dose. The MDMA-induced hyperthermia significantly contributed to the morbidity and mortality in this case series. Factors contributing to the severity of the hyperthermia include ingestion of large doses of MDMA, a warm ambient environment, and physical exertion.

Systematic review on the use of activated charcoal for gastrointestinal decontamination following acute oral overdose.

INTRODUCTION: The use of activated charcoal in poisoning remains both a pillar of modern toxicology and a source of debate. Following the publication of the joint position statements on the use of single-dose and multiple-dose activated charcoal by the American Academy of Clinical Toxicology and the European Association of Poison Centres and Clinical Toxicologists, the routine use of activated charcoal declined. Over subsequent years, many new pharmaceuticals became available in modified or alternative-release formulations and additional data on gastric emptying time in poisoning was published, challenging previous assumptions about absorption kinetics. The American Academy of Clinical Toxicology, the European Association of Poison Centres and Clinical Toxicologists and the Asia Pacific Association of Medical Toxicology founded the Clinical Toxicology Recommendations Collaborative to create a framework for evidence-based recommendations for the management of poisoned patients. The activated charcoal workgroup of the Clinical Toxicology Recommendations Collaborative was tasked with reviewing systematically the evidence pertaining to the use of activated charcoal in poisoning in order to update the previous recommendations. OBJECTIVES: The main objective was: Does oral activated charcoal given to adults or children prevent toxicity or improve clinical outcome and survival of poisoned patients compared to those who do not receive charcoal?  Secondary objectives were to evaluate pharmacokinetic outcomes, the role of cathartics, and adverse events to charcoal administration. This systematic review summarizes the available evidence on the efficacy of activated charcoal. METHODS: A medical librarian created a systematic search strategy for Medline (Ovid), subsequently translated for Embase (via Ovid), CINAHL (via EBSCO), BIOSIS Previews (via Ovid), Web of Science, Scopus, and the Cochrane Library/DARE. All databases were searched from inception to December 31, 2019. There were no language limitations.  One author screened all citations identified in the search based on predefined inclusion/exclusion criteria. Excluded citations were confirmed by an additional author and remaining articles were obtained in full text and evaluated by at least two authors for inclusion. All authors cross-referenced full-text articles to identify articles missed in the searches. Data from included articles were extracted by the authors on a standardized spreadsheet and two authors used the GRADE methodology to independently assess the quality and risk of bias of each included study. RESULTS: From 22,950 titles originally identified, the final data set consisted of 296 human studies, 118 animal studies, and 145 in vitro studies. Also included were 71 human and two animal studies that reported adverse events. The quality was judged to have a Low or Very Low GRADE in 469 (83%) of the studies. Ninety studies were judged to be of Moderate or High GRADE. The higher GRADE studies reported on the following drugs: paracetamol (acetaminophen), phenobarbital, carbamazepine, cardiac glycosides (digoxin and oleander), ethanol, iron, salicylates, theophylline, tricyclic antidepressants, and valproate. Data on newer pharmaceuticals not reviewed in the previous American Academy of Clinical Toxicology/European Association of Poison Centres and Clinical Toxicologists statements such as quetiapine, olanzapine, citalopram, and Factor Xa inhibitors were included. No studies on the optimal dosing for either single-dose or multiple-dose activated charcoal were found. In the reviewed clinical data, the time of administration of the first dose of charcoal was beyond one hour in 97% (n = 1006 individuals), beyond two hours in 36% (n = 491 individuals), and beyond 12 h in 4% (n = 43 individuals) whereas the timing of the first dose in controlled studies was within one hour of ingestion in 48% (n = 2359 individuals) and beyond two hours in 36% (n = 484) of individuals. CONCLUSIONS: This systematic review found heterogenous data. The higher GRADE data was focused on a few select poisonings, while studies that addressed patients with unknown and or mixed ingestions were hampered by low rates of clinically meaningful toxicity or death.  Despite these limitations, they reported a benefit of activated charcoal beyond one hour in many clinical scenarios.

Clinical utility of an LC-MS/MS seizure panel for common drugs involved in drug-induced seizures.

BACKGROUND: Approximately 6% of new-onset seizures are drug-related, but there is currently no reliable way to determine if a seizure is drug-induced. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful tool that allows simultaneous detection of numerous analytes of diverse chemical nature in patient samples. This allows a single analysis to incorporate many compounds relevant to a particular clinical presentation, such as suspected drug-induced seizures. We investigated whether results from a seizure panel using LC-MS/MS could affect patient care. METHODS: We developed a semiquantitative LC-MS/MS assay to detect 12 chemically diverse drugs implicated in drug-related seizures. We collected leftover serum and plasma samples from patients who had seized, performed solid-phase extraction, and analyzed the samples using a hybrid triple quadrupole/linear ion trap mass spectrometer. After assembling a team of medical and toxicology experts, we developed and used a scoring system to determine whether the results of the seizure panel would have affected patient treatment in each case where a drug was detected. RESULTS: In an analysis of 157 samples from patients who seized, 17 (11%) were found to be positive for a drug on the seizure panel. The team of experts determined that the test results probably or definitely would have affected treatment in 7 (41%) of these cases. CONCLUSIONS: A test that detects the presence of drugs implicated in drug-induced seizures can help physicians determine if an unexplained seizure is drug-related and thus potentially better direct patient care. Additionally, LC-MS/MS is an effective tool for answering clinically driven questions.

Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care.

STUDY OBJECTIVE: We developed recommendations for antidote stocking at hospitals that provide emergency care. METHODS: An expert panel representing diverse perspectives (clinical pharmacology, clinical toxicology, critical care medicine, clinical pharmacy, emergency medicine, internal medicine, pediatrics, poison centers, pulmonary medicine, and hospital accreditation) was formed to create recommendations for antidote stocking. Using a standardized summary of the medical literature, the primary reviewer for each antidote proposed guidelines for antidote stocking to the full panel. The panel used a formal iterative process to reach their recommendation for the quantity of an antidote that should be stocked and the acceptable period for delivery of each antidote. RESULTS: The panel recommended consideration of 24 antidotes for stocking. The panel recommended that 12 of the antidotes be available for immediate administration on patient arrival. In most hospitals, this period requires that the antidote be stocked in the emergency department. Another 9 antidotes were recommended for availability within 1 hour of the decision to administer, allowing the antidote to be stocked in the hospital pharmacy if the hospital has a mechanism for prompt delivery of antidotes. The panel identified additional antidotes that should be stocked by the hospital but are not usually needed within the first hour of treatment. The panel recommended that each hospital perform a formal antidote hazard vulnerability assessment to determine the need for antidote stocking in that hospital. CONCLUSION: The antidote expert recommendations provide a tool to be used in creating practices for appropriate and adequate antidote stocking in hospitals that provide emergency care.

Acute quetiapine overdose in adults: a 5-year retrospective case series.

STUDY OBJECTIVE: To describe clinical effects and outcome after acute quetiapine overdose in adults and compare these with overdose by all other antipsychotic drugs as a group. METHODS: We performed a 5-year (2002 to 2006) retrospective case series by chart review of the California Poison Control System database for adult patients with acute ingestion of quetiapine. Patients with coingestants were excluded. Symptoms, signs, and medical outcomes were extracted from the database and also by direct chart review for some variables (QRS- and QT-interval prolongation, torsades de pointes). RESULTS: We found 945 cases meeting criteria for analysis. Intentional ingestions accounted for 87% of cases. Patient ages ranged from 18 to 84 years, with a median of 35 years. There were 3 deaths, all of whom had coma, tachycardia, and respiratory depression requiring ventilatory support. Clinical manifestations included drowsiness (76%), coma (10%), seizures (2%), tachycardia (56%), hypotension (18%), and respiratory depression (5%). There were insufficient data to determine the incidence of QRS or QT prolongation in our study group, but only 2 patients were reported to have ventricular tachycardia and neither was described as having torsades de pointes. Compared with overdose by all other antipsychotic agents as a group, quetiapine was more likely to cause hypotension (odds ratio [OR] 2.05; 95% confidence interval [CI] 1.52 to 2.76), coma (OR 2.16; 95% CI 1.46 to 3.20), and respiratory depression (OR 2.49; 95% CI 1.40 to 4.41); require tracheal intubation (OR 1.92; 95% CI 1.41 to 2.61); and result in death or a major medical outcome (OR 2.62; 95% CI 1.78 to 3.85). CONCLUSION: Consequences of acute quetiapine overdose included coma, respiratory depression, and hypotension, and these complications were more common compared with overdose by all other antipsychotic agents as a group.

Safety and effectiveness of physostigmine: a 10-year retrospective review.

BACKGROUND: Physostigmine has long been recognized as an antidote to reverse anticholinergic delirium. However, its effectiveness, safety profile, and dosing have been disputed. OBJECTIVES: To describe effectiveness, adverse events, and dosing associated with the use of physostigmine to reverse anticholinergic delirium. METHODS: A retrospective cohort study of hospitalized patients reported to a regional poison center system between 2003 and 2012 who received physostigmine to reverse an anticholinergic toxidrome. Data extraction of a priori defined variables were recorded with concurrence of investigators. The cases were stratified by the primary ingestant as the presumed causative agent and associations for response were performed using odds ratios (ORs), 95% confidence intervals (CI's), and p values. RESULTS: Of the 1422 cases identified, 191 met the inclusion criteria. Patients exposed to non-diphenhydramine antihistamines (n = 14), antipsychotics (n = 4), and tricyclic antidepressants (n = 3) had 100% response to physostigmine, whereas anticholinergic plants (n = 46/67; 68.7%, OR: 0.70; CI: 0.36-1.35), diphenhydramine (n = 43/56; 64.2%, OR: 1.30; CI: 0.63-2.68), and combination products (n = 8/10; 80%, OR: 1.48; CI: 0.30-7.24) had partial response rates. Of the included patients, 142 (74.3%) were treated with physostigmine alone, and 16 (8.4%) of these patients were discharged directly from the emergency department (ED). DISCUSSION: Most patients, 182 (95.3%), had no documented adverse effects. Four patients (2.1%) experienced emesis, two experienced QTc prolongation (1.0%), and two experienced seizures (1.0%). There was a single fatality 6 h after physostigmine administration. Average initial total doses of physostigmine ranged from 1.0 to 1.75 mg. Most patients were admitted to the ICU (n = 110; 57.6%), however, 36 (18.8%) patients were discharged directly from the ED. CONCLUSIONS: In this retrospective cohort study, physostigmine administration to reverse anticholinergic delirium had a good safety profile, and often improved or resolved anticholinergic delirium when administered in doses less than 2 mg.

Patterns of ecstasy-associated hyponatremia in California.

STUDY OBJECTIVE: We describe the clinical characteristics of patients with ecstasy- (3,4-methylenedioxymethamphetamine [MDMA]) associated hyponatremia (serum sodium level <130 mmol/L) reported to the California Poison Control System during a 5-year period and determine whether a sex difference exists among patients with ecstasy-associated hyponatremia and hyponatremia-associated adverse outcomes. METHODS: We performed a retrospective review of cases involving ecstasy intoxication reported to the California Poison Control System and recorded in its computerized database from January 1, 2000, through October 9, 2005. We excluded cases that did not involve MDMA exposure or in which there were no symptoms or were minimal effects only. Confirmation of exposure to MDMA was based on history of use and, when available, urine toxicology testing results positive for MDMA or amphetamine derivatives. Hyponatremia was defined as a measured serum sodium level less than 130 mmol/L. RESULTS: A total of 1,436 cases potentially involving ecstasy were reported to the California Poison Control System during the 5-year study period, of which 891 were excluded according to the criteria described above. Of the 545 cases that met inclusion criteria, 296 (54.3%) were women and 249 (45.7%) were men. There were 188 cases (34.5%) with a documented serum sodium level, of which 73 (38.8%) reported hyponatremia (Na <130 mmol/L). Of the 73 subjects with hyponatremia, 55 (75.3%) were women and 18 (24.7%) men; of the 115 nonhyponatremic subjects, 50 (43.5%) were women and 65 (56.5%) were men. Among patients with a documented serum sodium level, female sex was associated with increased odds of hyponatremia (odds ratio [OR] 4.0; 95% confidence interval [CI] 2.1 to 7.6). Among women, those with hyponatremia demonstrated increased odds of coma (OR 3.9; 95% CI 1.2 to 12.9), whereas among men, no increased odds of hyponatremia-associated coma were observed (OR 0.8; 95% CI 0.15 to 4.0). CONCLUSION: Female sex was associated with increased odds of hyponatremia and increased odds of hyponatremia-associated coma among persons with ecstasy intoxication and a documented serum sodium level reported to the California Poison Control System from 2000 to 2005. Multiple potential confounders, including spectrum bias, incomplete laboratory data, and individual differences in study subject characteristics, prevent determination of causality about sex differences in the incidence of ecstasy-associated hyponatremia and its complications.

Acute amlodipine overdose treated by high dose intravenous calcium in a patient with severe renal insufficiency.

Calcium salts are frequently used in the treatment of calcium antagonist poisoning. Different dosing regimens have been employed. The major risk of high dose calcium therapy is iatrogenic hypercalcemia, especially in patients with diminished renal function. Repeated doses of calcium are therefore often avoided; however, inadequate use of intravenous calcium may cause treatment failure in severe calcium antagonist overdose. We report our experience of using high dose intravenous calcium chloride effectively and safely to treat severe amlodipine overdose in a patient with severe renal insufficiency.

Lamotrigine-induced seizures in a child: case report and literature review.

INTRODUCTION: Lamotrigine is an antiepileptic agent. There is only one previous report of a seizure associated with lamotrigine overdose with laboratory confirmation (a 2-year-old girl, lamotrigine level of 3.8 mg/L). CASE REPORT: A healthy 19-month-old boy ingested an unknown amount of his sister's lamotrigine tablets. Twenty minutes later, the child experienced generalized seizure activity lasting 10 seconds, followed by another brief self-limited seizure. Vitals signs: heart rate 152-207 bpm crying, respiratory rate 26 /min, temperature 95.7 degrees F, and pupils 3mm. The one-hour lamotrigine level = 20.3 mg/L. The child was discharged 24 hours later. LITERATURE REVIEW: Six previous case reports of lamotrigine poisoning with serum levels, as well as a retrospective review of lamotrigine exposures, are discussed. CONCLUSION: A case of lamotrigine-induced seizures in a pediatric patient is reported, with a level approximately five times the upper limit of the therapeutic range. The pediatric population may be at increased risk of seizures following lamotrigine poisoning, and serum levels may not be clinically useful for predicting outcome after overdose.

Methylphenidate poisoning: an evidence-based consensus guideline for out-of-hospital management.

A review of US poison center data for 2004 showed over 8,000 ingestions of methylphenidate. A guideline that determines the conditions for emergency department referral and prehospital care could potentially optimize patient outcome, avoid unnecessary emergency department visits, reduce health care costs, and reduce life disruption for patients and caregivers. An evidence-based expert consensus process was used to create the guideline. Relevant articles were abstracted by a trained physician researcher. The first draft of the guideline was created by the lead author. The entire panel discussed and refined the guideline before distribution to secondary reviewers for comment. The panel then made changes based on the secondary review comments. The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial out-of-hospital management of patients with suspected ingestions of methylphenidate by 1) describing the process by which a specialist in poison information should evaluate an exposure to methylphenidate, 2) identifying the key decision elements in managing cases of methylphenidate ingestion, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This review focuses on the ingestion of more than a single therapeutic dose of methylphenidate and the effects of an overdose and is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and the health professionals providing care, considering all of the circumstances involved. This guideline does not substitute for clinical judgment. Recommendations are in chronological order of likely clinical use. The grade of recommendation is in parentheses. 1) All patients with suicidal intent, intentional abuse, or in cases in which a malicious intent is suspected (e.g., child abuse or neglect) should be referred to an emergency department (Grade D). 2) In patients without evidence of self-harm, abuse, or malicious intent, poison center personnel should elicit additional information including the time of the ingestion, the precise dose ingested, and the presence of coingestants (Grade D). 3) Patients who are chronically taking a monoamine oxidase inhibitor and who have ingested any amount of methylphenidate require referral to an emergency department (Grade D). 4) Patients experiencing any changes in behavior other than mild stimulation or agitation should be referred to an emergency department. Examples of moderate to severe symptoms that warrant referral include moderate-to-severe agitation, hallucinations, abnormal muscle movements, headache, chest pain, loss of consciousness, or convulsions (Grade D). 5) For patients referred to an emergency department, transportation via ambulance should be considered based on several factors including the condition of the patient and the length of time it will take for the patient to arrive at the emergency department (Grade D). 6) If the patient has no symptoms, and more than 3 hours have elapsed between the time of ingestion and the call to the poison center, referral to an emergency department is not recommended (Grade D). 7) Patients with acute or acute-on-chronic ingestions of less than a toxic dose (see recommendations 8, 9, and 10) or chronic exposures to methylphenidate with no or mild symptoms can be observed at home with instructions to call the poison center back if symptoms develop or worsen. For acute-on-chronic ingestions, the caller should be instructed not to administer methylphenidate to the patient for the next 24 hours. The poison center should consider making a follow-up call at approximately 3 hours after ingestion (Grade D). 8) Patients who ingest more than 2 mg/kg or 60 mg, whichever is less, of an immediate-release formulation (or the equivalent amount of a modified-release formulation that has been chewed) should be referred to an emergency department (Grade C). 9) If a patch has been swallowed, consider the entire contents of the patch (not just the labeled dose of the patch) to have been ingested. Patients who ingest more than 2 mg/kg or 60 mg, whichever is less should be referred to an emergency department. If it is known that the patch has been chewed only briefly, and the patch remains intact, significant toxicity is unlikely and emergency department referral is not necessary (Grade D). 10) Patients who ingest more than 4 mg/kg or 120 mg, whichever is less, of an intact modified-release formulation should be referred to an emergency department (Grade D). 11) For oral exposures, do not induce emesis (Grade D). 12) Pre-hospital activated charcoal administration, if available, should only be carried out by health professionals and only if no contraindications are present. Do not delay transportation in order to administer activate charcoal (Grade D). 13) Benzodiazepines can be administered by EMS personnel if agitation, dystonia, or convulsions are present and if authorized by EMS medical direction expressed by written treatment protocol or policy or direct medical oversight (Grade C). 14) Standard advanced cardiac life support (ACLS) measures should be administered by EMS personnel if respiratory arrest, cardiac dysrhythmias, or cardiac arrest are present and if authorized by EMS medical direction expressed by written treatment protocol or policy or direct medical oversight (Grade C).

Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management.

A review of U.S. poison center data for 2004 showed over 12,000 exposures to tricyclic antidepressants (TCAs). A guideline that determines the conditions for emergency department referral and prehospital care could potentially optimize patient outcome, avoid unnecessary emergency department visits, reduce healthcare costs, and reduce life disruption for patients and caregivers. An evidence-based expert consensus process was used to create the guideline. Relevant articles were abstracted by a trained physician researcher. The first draft of the guideline was created by the lead author. The entire panel discussed and refined the guideline before distribution to secondary reviewers for comment. The panel then made changes based on the secondary review comments. The objective of this guideline is to assist poison center personnel in the appropriate prehospital triage and management of patients with suspected ingestions of TCAs by 1) describing the manner in which an ingestion of a TCA might be managed, 2) identifying the key decision elements in managing cases of TCA ingestion, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This guideline applies to ingestion of TCAs alone. Co-ingestion of additional substances could require different referral and management recommendations depending on their combined toxicities. This guideline is based on the assessment of current scientific and clinical information. The panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and the health professionals providing care, considering all the circumstances involved. This guideline does not substitute for clinical judgment. Recommendations are in chronological order of likely clinical use. The grade of recommendation is in parentheses. 1) Patients with suspected self-harm or who are the victims of malicious administration of a TCA should be referred to an emergency department immediately (Grade D). 2) Patients with acute TCA ingestions who are less than 6 years of age and other patients without evidence of self-harm should have further evaluation including standard history taking and determination of the presence of co-ingestants (especially other psychopharmaceutical agents) and underlying exacerbating conditions, such as convulsions or cardiac arrhythmias. Ingestion of a TCA in combination with other drugs might warrant referral to an emergency department. The ingestion of a TCA by a patient with significant underlying cardiovascular or neurological disease should cause referral to an emergency department at a lower dose than for other individuals. Because of the potential severity of TCA poisoning, transportation by EMS, with close monitoring of clinical status and vital signs en route, should be considered (Grade D). 3) Patients who are symptomatic (e.g., weak, drowsy, dizzy, tremulous, palpitations) after a TCA ingestion should be referred to an emergency department (Grade B). 4) Ingestion of either of the following amounts (whichever is lower) would warrant consideration of referral to an emergency department: an amount that exceeds the usual maximum single therapeutic dose or an amount equal to or greater than the lowest reported toxic dose. For all TCAs except desipramine, nortriptyline, trimipramine, and protriptyline, this dose is >5 mg/kg. For despiramine it is >2.5 mg/kg; for nortriptyline it is >2.5 mg/kg; for trimipramine it is >2.5 mg/kg; and for protriptyline it is >1 mg/kg. This recommendation applies to both patients who are naïve to the specific TCA and to patients currently taking cyclic antidepressants who take extra doses, in which case the extra doses should be added to the daily dose taken and then compared to the threshold dose for referral to an emergency department (Grades B/C). 5) Do not induce emesis (Grade D). 6) The risk-to-benefit ratio of prehospital activated charcoal for gastrointestinal decontamination in TCA poisoning is unknown. Prehospital activated charcoal administration, if available, should only be carried out by health professionals and only if no contraindications are present. Do not delay transportation in order to administer activated charcoal (Grades B/D). 7) For unintentional poisonings, asymptomatic patients are unlikely to develop symptoms if the interval between the ingestion and the initial call to a poison center is greater than 6 hours. These patients do not need referral to an emergency department facility (Grade C). 8) Follow-up calls to determine the outcome for a TCA ingestions ideally should be made within 4 hours of the initial call to a poison center and then at appropriate intervals thereafter based on the clinical judgment of the poison center staff (Grade D). 9) An ECG or rhythm strip, if available, should be checked during the prehospital assessment of a TCA overdose patient. A wide-complex arrhythmia with a QRS duration longer than 100 msec is an indicator that the patient should be immediately stabilized, given sodium bicarbonate if there is a protocol for its use, and transported to an emergency department (Grade B). 10) Symptomatic patients with TCA poisoning might require prehospital interventions, such as intravenous fluids, cardiovascular agents, and respiratory support, in accordance with standard ACLS guidelines (Grade D). 11) Administration of sodium bicarbonate might be beneficial for patients with severe or life-threatening TCA toxicity if there is a prehospital protocol for its use (Grades B/D). 12) For TCA-associated convulsions, benzodiazepines are recommended (Grade D). 13) Flumazenil is not recommended for patients with TCA poisoning (Grade D).

Long-acting anticoagulant rodenticide poisoning: an evidence-based consensus guideline for out-of-hospital management.

The objective of this guideline is to assist poison center personnel in the out-of-hospital triage and initial management of patients with suspected exposure to long-acting anticoagulant rodenticides (LAAR). An evidence-based expert consensus process was used to create this guideline. It is based on an assessment of current scientific and clinical information. The panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and health professionals providing care. The grade of recommendation is in parentheses. 1) Patients with exposure due to suspected self-harm, abuse, misuse, or potentially malicious administration should be referred to an emergency department immediately regardless of the doses reported (Grade D). 2) Patients with symptoms of LAAR poisoning (e.g., bleeding, bruising) should be referred immediately to an emergency department for evaluation regardless of the doses reported (Grade C). 3) Patients with chronic ingestion of LAAR should be referred immediately to an emergency department for evaluation of intent and potential coagulopathy (Grade B). 4) Patients taking anticoagulants therapeutically and who ingest any dose of a LAAR should have a baseline prothrombin time measured and then again at 48-72 hours after ingestion (Grade D). 5) Patients with unintentional ingestion of less than 1 mg of LAAR active ingredient can be safely observed at home without laboratory monitoring. This includes practically all unintentional ingestions in children less than 6 years of age (Grade C). 6) Pregnant patients with unintentional exposure to less than 1 mg of LAAR active ingredient should be evaluated by their obstetrician or primary care provider as an outpatient. Immediate referral to an ED or clinic is not required (Grade D). 7) Patients with unintentional ingestion of 1 mg or more of active ingredient and are asymptomatic should be evaluated for coagulopathy at 48-72 hours after exposure (Grade B). 8) Physicians' offices or outpatient clinics must be able to obtain coagulation study results in a timely manner, preferably in less than 24 hours, for patients who require outpatient monitoring (Grade D). 9) Gastrointestinal decontamination with ipecac syrup or gastric lavage is not recommended (Grade D). 10) Transportation to an emergency department should not be delayed for administration of activated charcoal (Grade D). 11) Patients with dermal exposures should be decontaminated by washing the skin with mild soap and water (Grade D). 12) The administration of vitamin K is not recommended prior to evaluation for coagulopathy (Grade D).