E. Martin Caravati

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

The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial management of patients with suspected ingestions of acetaminophen. An evidence-based expert consensus process was used to create this guideline. This guideline applies to ingestion of acetaminophen alone 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. The panels recommendations follow. These recommendations are provided in chronological order of likely clinical use. The grade of recommendation is provided in parentheses. 1) The initial history obtained by the specialist in poison information should include the patients age and intent (Grade B), the specific formulation and dose of acetaminophen, the ingestion pattern (single or multiple), duration of ingestion (Grade B), and concomitant medications that might have been ingested (Grade D). 2) Any patient with stated or suspected self-harm or who is the recipient of a potentially malicious administration of acetaminophen should be referred to an emergency department immediately regardless of the amount ingested. This referral should be guided by local poison center procedures (Grade D). 3) Activated charcoal can be considered if local poison center policies support its prehospital use, a toxic dose of acetaminophen has been taken, and fewer than 2 hours have elapsed since the ingestion (Grade A). Gastrointestinal decontamination could be particularly important if acetylcysteine cannot be administered within 8 hours of ingestion. Acute, single, unintentional ingestion of acetaminophen: 1) Any patient with signs consistent with acetaminophen poisoning (e.g., repeated vomiting, abdominal tenderness in the right upper quadrant or mental status changes) should be referred to an emergency department for evaluation (Grade D). 2) Patients less than 6 years of age should be referred to an emergency department if the estimated acute ingestion amount is unknown or is 200 mg/kg or more. Patients can be observed at home if the dose ingested is less than 200 mg/kg (Grade B). 3) Patients 6 years of age or older should be referred to an emergency department if they have ingested at least 10 g or 200 mg/kg (whichever is lower) or when the amount ingested is unknown (Grade D). 4) Patients referred to an emergency department should arrive in time to have a stat serum acetaminophen concentration determined at 4 hours after ingestion or as soon as possible thereafter. If the time of ingestion is unknown, the patient should be referred to an emergency department immediately (Grade D). 5) If the initial contact with the poison center occurs more than 36 hours after the ingestion and the patient is well, the patient does not require further evaluation for acetaminophen toxicity (Grade D). Repeated supratherapeutic ingestion of acetaminophen (RSTI): 1) Patients under 6 years of age should be referred to an emergency department immediately if they have ingested: a) 200 mg/kg or more over a single 24-hour period, or b) 150 mg/kg or more per 24-hour period for the preceding 48 hours, or c) 100 mg/kg or more per 24-hour period for the preceding 72 hours or longer (Grade C). 2) Patients 6 years of age or older should be referred to an emergency department if they have ingested: a) at least 10 g or 200 mg/kg (whichever is less) over a single 24-hour period, or b) at least 6 g or 150 mg/kg (whichever is less) per 24-hour period for the preceding 48 hours or longer. In patients with conditions purported to increase susceptibility to acetaminophen toxicity (alcoholism, isoniazid use, prolonged fasting), the dose of acetaminophen considered as RSTI should be greater than 4 g or 100 mg/kg (whichever is less) per day (Grade D). 3) Gastrointestinal decontamination is not needed (Grade D). Other recommendations: 1) The out-of-hospital management of extended-release acetaminophen or multi-drug combination products containing acetaminophen is the same as an ingestion of acetaminophen alone (Grade D). However, the effects of other drugs might require referral to an emergency department in accordance with the poison centers normal triage criteria. 2) The use of cimetidine as an antidote is not recommended (Grade A).

Iron ingestion: an evidence-based consensus guideline for out-of-hospital management.

From 1983 to 1991, iron caused over 30% of the deaths from accidental ingestion of drug products by children. An evidence-based expert consensus process was used to create this guideline. Relevant articles were abstracted by a trained physician researcher. The first draft of the guideline was created by the primary author. The entire panel discussed and refined the guideline before its distribution to secondary reviewers for comment. The panel then made changes in response to comments received. The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial management of patients with suspected ingestions of iron by 1) describing the manner in which an ingestion of iron might be managed, 2) identifying the key decision elements in managing cases of iron 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 iron alone 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. The panels recommendations follow; the grade of recommendation is in parentheses. 1) Patients with stated or suspected self-harm or who are victims of malicious administration of an iron product should be referred to an acute care medical facility immediately. This activity should be guided by local poison center procedures. In general, this should occur regardless of the amount ingested (Grade D). 2) Pediatric or adult patients with a known ingestion of 40 mg/kg or greater of elemental iron in the form of adult ferrous salt formulations or who have severe or persistent symptoms related to iron ingestion should be referred to a healthcare facility for medical evaluation. Patients who have ingested less than 40 mg/kg of elemental iron and who are having mild symptoms can be observed at home. Mild symptoms such as vomiting and diarrhea occur frequently. These mild symptoms should not necessarily prompt referral to a healthcare facility. Patients with more serious symptoms, such as persistent vomiting and diarrhea, alterations in level of consciousness, hematemesis, and bloody diarrhea require referral. The same dose threshold should be used for pregnant women, however, when calculating the mg/kg dose ingested, the pre-pregnancy weight of the woman should be used (Grade C). 3) Patients with ingestions of childrens chewable vitamins plus iron should be observed at home with appropriate follow-up. The presence of diarrhea should not be the sole indicator for referral as these products are often sweetened with sorbitol. Children may need referral for the management of dehydration if vomiting or diarrhea is severe or prolonged (Grade C). 4) Patients with unintentional ingestions of carbonyl iron or polysaccharide-iron complex formulations should be observed at home with appropriate follow-up (Grade C). 5) Ipecac syrup, activated charcoal, cathartics, or oral complexing agents, such as bicarbonate or phosphate solutions, should not be used in the out-of-hospital management of iron ingestions (Grade C). 6) Asymptomatic patients are unlikely to develop symptoms if the interval between ingestion and the call to the poison center is greater than 6 hours. These patients should not need referral or prolonged observation. Depending on the specific circumstances, follow-up calls might be indicated (Grade C).

Acute hydrofluoric acid exposure

Significant local and systemic toxicity may occur from hydrofluoric acid by all routes of exposure. Prompt decontamination by removal from the source and copious irrigation of eyes and skin are essential to reduce morbidity and mortality. Ingestion of small amounts of HF can lead to rapid systemic poisoning and death. Calcium gluconate therapy has become the preferred method of detoxifying the fluoride ion, although its efficacy is based mainly on anecdotal reports and poorly controlled clinical studies. Therefore, more basic research is needed to elucidate the pathophysiology of local toxicity and the best therapeutic modalities to limit injury. All significant exposures should be evaluated by health care personnel familiar with the potential toxicity of this compound.

Salicylate poisoning: An evidence-based consensus guideline for out-of-hospital management

A review of U.S. poison center data for 2004 showed over 40,000 exposures to salicylate-containing products. A guideline that determines the conditions for emergency department referral and pre-hospital 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 a suspected exposure to salicylates by 1) describing the process by which a specialist in poison information should evaluate an exposure to salicylates, 2) identifying the key decision elements in managing cases of salicylate exposure, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This guideline 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) Patients with stated or suspected self-harm or who are the victims of a potentially malicious administration of a salicylate, should be referred to an emergency department immediately. This referral should be guided by local poison center procedures. In general, this should occur regardless of the dose reported (Grade D). 2) The presence of typical symptoms of salicylate toxicity such as hematemesis, tachypnea, hyperpnea, dyspnea, tinnitus, deafness, lethargy, seizures, unexplained lethargy, or confusion warrants referral to an emergency department for evaluation (Grade C). 3) Patients who exhibit typical symptoms of salicylate toxicity or nonspecific symptoms such as unexplained lethargy, confusion, or dyspnea, which could indicate the development of chronic salicylate toxicity, should be referred to an emergency department (Grade C). 4) Patients without evidence of self-harm should have further evaluation, including determination of the dose, time of ingestion, presence of symptoms, history of other medical conditions, and the presence of co-ingestants. The acute ingestion of more than 150 mg/kg or 6.5 g of aspirin equivalent, whichever is less, warrants referral to an emergency department. Ingestion of greater than a lick or taste of oil of wintergreen (98% methyl salicylate) by children under 6 years of age and more than 4 mL of oil of wintergreen by patients 6 years of age and older could cause systemic salicylate toxicity and warrants referral to an emergency department (Grade C). 5) Do not induce emesis for ingestions of salicylates (Grade D). 6) Consider the out-of-hospital administration of activated charcoal for acute ingestions of a toxic dose if it is immediately available, no contraindications are present, the patient is not vomiting, and local guidelines for its out-of-hospital use are observed. However, do not delay transportation in order to administer activated charcoal (Grade D). 7) Women in the last trimester of pregnancy who ingest below the dose for emergency department referral and do not have other referral conditions should be directed to their primary care physician, obstetrician, or a non-emergent health care facility for evaluation of maternal and fetal risk. Routine referral to an emergency department for immediate care is not required (Grade C). 8) For asymptomatic patients with dermal exposures to methyl salicylate or salicylic acid, the skin should be thoroughly washed with soap and water and the patient can be observed at home for development of symptoms (Grade C). 9) For patients with an ocular exposure of methyl salicylate or salicylic acid, the eye(s) should be irrigated with room-temperature tap water for 15 minutes. If after irrigation the patient is having pain, decreased visual acuity, or persistent irritation, referral for an ophthalmological examination is indicated (Grade D). 10) Poison centers should monitor the onset of symptoms whenever possible by conducting follow-up calls at periodic intervals for approximately 12 hours after ingestion of non-enteric-coated salicylate products, and for approximately 24 hours after the ingestion of enteric-coated aspirin (Grade C).

Massive dextromethorphan ingestion and abuse

The case of a 23-year-old man who was acutely intoxicated on dextromethorphan and who was chronically addicted to the drug is described. He consumed the highest daily dose for the longest duration yet reported in the worlds English-language medical literature. Toxicity, abuse potential, and therapy of dextromethorphan intoxication are discussed.

Histamine antagonists in the treatment of acute allergic reactions

STUDY OBJECTIVE We compared the efficacies of cimetidine (an H2-receptor antagonist) and diphenhydramine (an H1-receptor antagonist) alone and in combination for alleviation of symptoms of acute allergic reactions. STUDY DESIGN AND INTERVENTIONS: In this prospective, randomized, double-blind study, patients and examiners assessed the severity of symptoms and signs of acute allergic reactions using a visual-analog scale before treatment and 30 minutes after treatment with 300 mg IV cimetidine and placebo, 50 mg IV diphenhydramine and placebo, or diphenhydramine plus cimetidine. SETTING AND PARTICIPANTS Thirty-nine patients with acute allergic reactions presenting to two emergency departments of teaching hospitals. RESULTS Of the 35 patients with pruritus, all 12 receiving diphenhydramine placebo had clinically significant relief compared with six of ten (60%) receiving cimetidine plus placebo (P = .03). Twelve of 13 (92%) receiving diphenhydramine plus cimetidine had relief, which was not a significant difference from the single drugs. Comparison of mean differences in pretreatment and post-treatment symptom scores (relief scores) among groups of patients with pruritus detected significantly more relief in the group receiving diphenhydramine plus placebo (80.3 +/- 7.4) than in those receiving cimetidine plus placebo (48.8 +/- 13.4) (P = .022). Of the 33 patients with urticaria, five of 11 (46%) receiving diphenhydramine plus placebo had clinically significant relief compared with eight of ten (80%) receiving cimetidine plus placebo (P = .18). Eleven of 12 patients (92%) receiving diphenhydramine plus cimetidine had relief, which is a significant difference from those receiving diphenhydramine plus placebo (P = .027). Comparison of mean relief scores in patients with urticaria detected significantly more relief in the group receiving diphenhydramine plus cimetidine (55.3 +/- 6.5) than in the group receiving diphenhydramine plus placebo (30.7 +/- 6.1) (P = .006). CONCLUSION For treatment of pruritus from acute allergic reactions, diphenhydramine is more effective than cimetidine, and the combination offers no additional benefit. For treatment of acute urticaria, the combination of cimetidine and diphenhydramine is more effective than diphenhydramine alone.

Terminal 40-ms frontal plane QRS axis as a marker for tricyclic antidepressant overdose

Tricyclic antidepressant (TCA) poisoning has been reported to cause a right-axis deviation of 130 degrees to 270 degrees in the terminal 40-ms frontal plane QRS axis (T40-ms axis) of the ECG. This retrospective cohort study was designed to determine if the T40-ms axis could discriminate TCA-toxic patients from other overdose patients and whether a correlation exists between TCA plasma concentration and T40-ms axis rotation. Only symptomatic overdose patients with plasma and urine drug screens and an ECG obtained within two hours of each other were included in the study. Patients were divided into two groups: TCA overdose patients (TCA OD, n = 48) and nonTCA overdose patients (nonTCA OD, n = 30). The mean T40-ms axis was significantly more rightward in the TCA OD group compared with the nonTCA OD group (179 +/- 74 vs 86 +/- 87, P less than .001). A TCA OD patient was 8.6 times more likely to have a T40-ms axis of more than 120 degrees than was a nonTCA OD patient (odds ratio, 8.6; 95% confidence interval, 2.7 to 29.1). Eight of the TCA poisoned patients (17%) did not demonstrate a T40-ms axis between 120 degrees and 270 degrees. Receiver operating characteristics demonstrated that the T40-ms axis was a better indicator of TCA toxicity than the QRS interval (P less than .05). A T40-ms axis of 120 degrees or more was 83% sensitive and 63% specific for TCA overdose. A correlation between plasma TCA concentration and T40-ms axis deviation was not found (r = .04).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Dextromethorphan poisoning: An evidence-based consensus guideline for out-of-hospital management

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 a suspected ingestion of dextromethorphan by 1) describing the process by which an ingestion of dextromethorphan might be managed, 2) identifying the key decision elements in managing cases of dextromethorphan ingestion, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This guideline applies to the ingestion of dextromethorphan alone. Co-ingestion of additional substances could require different referral and management recommendations depending on the combined toxicities of the substances. This guideline is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions might 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. 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) Patients who exhibit more than mild effects (e.g., infrequent vomiting or somnolence [lightly sedated and arousable with speaking voice or light touch]) after an acute dextromethorphan ingestion should be referred to an emergency department (Grade C). 3) Patients who have ingested 5–7.5 mg/kg should receive poison center-initiated follow-up approximately every 2 hours for up to 4 hours after ingestion. Refer to an emergency department if more than mild symptoms develop (Grade D). 4) Patients who have ingested more than 7.5 mg/kg should be referred to an emergency department for evaluation (Grade C). 5) If the patient is taking other medications likely to interact with dextromethorphan and cause serotonin syndrome, such as monoamine oxidase inhibitors or selective serotonin reuptake inhibitors, poison center-initiated follow-up every 2 hours for 8 hours is recommended (Grade D). 6) Patients who are asymptomatic and more than 4 hours have elapsed since the time of ingestion can be observed at home (Grade C). 7) Do not induce emesis (Grade D). 8) Do not use activated charcoal at home. Activated charcoal can be administered to asymptomatic patients who have ingested overdoses of dextromethorphan within the preceding hour. Its 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 (Grade D). 9) For patients who have ingested dextromethorphan and are sedated or comatose, naloxone, in the usual doses for treatment of opioid overdose, can be considered for prehospital administration, particularly if the patient has respiratory depression (Grade C). 10) Use intravenous benzodiazepines for seizures and benzodiazepines and external cooling measures for hyperthermia (>104°F, >40°C) for serotonin syndrome. This should be done in consultation with and authorized by EMS medical direction, by a written treatment protocol or policy, or with direct medical oversight (Grade C). 11) Carefully ascertain by history whether other drugs, such as acetaminophen, were involved in the incident and assess the risk for toxicity or for a drug interaction.

Selective serotonin reuptake inhibitor poisoning: an evidence-based consensus guideline for out-of-hospital management

A review of US poison center data for 2004 showed over 48,000 exposures to selective serotonin reuptake inhibitors (SSRIs). 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 management of patients with a suspected ingestion of an SSRI by 1) describing the process by which an ingestion of an SSRI might be managed, 2) identifying the key decision elements in managing cases of SSRI 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 immediate-release forms of SSRIs alone. Co-ingestion of additional substances might require different referral and management recommendations depending on their combined toxicities. This guideline 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. This activity should be guided by local poison center procedures. In general, this should occur regardless of the dose reported (Grade D). 2) Any patient already experiencing any symptoms other than mild effects (mild effects include vomiting, somnolence [lightly sedated and arousable with speaking voice or light touch], mydriasis, or diaphoresis) should be transported to an emergency department. Transportation via ambulance should be considered based on the condition of the patient and the length of time it will take the patient to arrive at the emergency department (Grade D). 3) Asymptomatic patients or those with mild effects (defined above) following isolated unintentional acute SSRI ingestions of up to five times an initial adult therapeutic dose (i.e., citalopram 100 mg, escitalopram 50 mg, fluoxetine 100 mg, fluvoxamine 250 mg, paroxetine 100 mg, sertraline 250 mg) can be observed at home with instructions to call the poison center back if symptoms develop. For patients already on an SSRI, those with ingestion of up to five times their own single therapeutic dose can be observed at home with instructions to call the poison center back if symptoms develop (Grade D). 4) The poison center should consider making follow-up calls during the first 8 hours after ingestion, following its normal procedure. Consideration should be given to the time of day when home observation will take place. Observation during normal sleep hours might not reliably identify the onset of toxicity. Depending on local poison center policy, patients could be referred to an emergency department if the observation would take place during normal sleeping hours of the patient or caretaker (Grade D). 5) Do not induce emesis (Grade C). 6) The use of oral activated charcoal can be considered since the likelihood of SSRI-induced loss of consciousness or seizures is small. However, there are no data to suggest a specific clinical benefit. The routine use of out-of-hospital oral activated charcoal in patients with unintentional SSRI overdose cannot be advocated at this time (Grade C). 7) Use intravenous benzodiazepines for seizures and benzodiazepines and external cooling measures for hyperthermia (>104°F [>40°C]) for SSRI-induced serotonin syndrome. This should be done in consultation with and authorized by EMS medical direction, by a written treatment protocol or policy, or with direct medical oversight (Grade C).