Peter A. Chyka

Interactions of Warfarin with Garlic, Ginger, Ginkgo, or Ginseng: Nature of the Evidence

OBJECTIVE: To review and characterize the evidence describing potential interactions between warfarin and garlic, ginger, ginkgo, or ginseng. DATA SOURCES: Searches of MEDLINE (1966–1999), other bibliographic databases, several abstracting services, and tertiary references were conducted. STUDY SELECTION AND DATA EXTRACTION: Articles were examined by each author, and additional citations were obtained from the references of these articles. Preference was given to English-language articles of human studies. DATA SYNTHESIS: Evidence is lacking for an interaction of warfarin with garlic or ginger. One case report associates ginseng use with decreased warfarin-maintained anticoagulation effect. Another case report links concomitant use of ginkgo and warfarin with the development of intracerebral hemorrhage. Hemorrhage and bleeding tendencies were noted in four cases with ginkgo use and in three cases with garlic; in none of these cases were patients receiving warfarin. CONCLUSIONS: The true risks of these interactions and effects are difficult to characterize due to the limited number and nature of existing reports.

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).

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).

How many deaths occur annually from adverse drug reactions in the United States

PURPOSE The numbers of deaths attributed to adverse drug reactions by death certificates and by the Food and Drug Administrations (FDA) spontaneous postmarketing surveillance system (MedWatch) were compared in order to characterize national mortality statistics. METHODS Mortality statistics related to adverse drug reactions were obtained from national public-use databases of death certificates based on appropriate International Classification of Disease (ICD-9) codes and from MedWatch during 1995. The number of deaths, frequency distributions of sex and age groups, and rankings of drug categories associated with adverse reactions were compared. RESULTS During 1995, 206 deaths were attributed to adverse drug reactions on death certificates in the United States, whereas MedWatch tabulated 6,894 fatalities. The proportions of men and women were similar, and the majority of deaths involved persons 60 years of age and older, in both data sets. The rankings of drug categories associated with adverse drug reactions differed in the two data sets. CONCLUSION The numbers of deaths reported in these data sets varied 34-fold and were up to several 100-fold less than values based on extrapolations of surveillance programs. These differences indicate that better and more comprehensive data are needed to develop appropriate health care policies to improve drug safety.

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).

Diphenhydramine and Dimenhydrinate Poisoning: an Evidence-Based Consensus Guideline for Out-of-Hospital Management*

In 2003, there were 28,092 human exposures to diphenhydramine reported to poison centers in the US. A related drug, dimenhydrinate, is a less frequent cause of poisonings. Between January 2000 and June 2004, there were 2,534 reported dimenhydrinate ingestions in children less than 6 years of age. An evidence-based expert consensus process was used to create this guideline. Relevant articles were abstracted by a trained physician researcher. The first draft was created by the primary 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 diphenhydramine or dimenhydrinate, or a dermal exposure to diphenhydramine. 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. The panels recommendations for dermal or oral exposures to diphenhydramine or oral exposures to dimenhydrinate follow. 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 or dermal exposure, determination of the precise dose ingested, and the presence of co-ingestants (Grade D). 3) Patients experiencing any changes in behavior other than mild drowsiness or mild stimulation should be referred to an emergency department. Examples of moderate to severe symptoms that warrant referral include agitation, staring spells, inconsolable crying, hallucinations, abnormal muscle movements, loss of consciousness, seizures, or respiratory depression (Grade D). 4) For patients referred to the 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 the patient to arrive at the emergency department (Grade D). 5) If the patient has no symptoms, and more than 4 hours have elapsed between the time of diphenhydramine ingestion and the call to the poison center, referral to an emergency department is not recommended. For dermal exposures to diphenhydramine, if the patient has no symptoms and it has been more than 8 hours since the diphenhydramine was thoroughly removed from the skin, referral to an emergency department is not recommended (Grade D). 6) Patients with acute ingestions of less than a toxic dose of diphenhydramine, or chronic exposures to diphenhydramine and no or mild symptoms, can be observed at home with instructions to call the poison center back if symptoms develop or worsen. The poison center should consider making a follow-up call at approximately 4 hours after ingestion (Grade D). 7) Children less than 6 years of age who ingest at least 7.5 mg/kg of diphenhydramine should be referred to an emergency department (Grade D). 8) Patients 6 years of age and older who ingest at least 7.5 mg/kg or 300 mg of diphenhydramine (whichever is less), should be referred to an emergency department (Grade D). 9) If the patient has no symptoms, and more than 6 hours have elapsed between the time of dimenhydrinate ingestion and the call to the poison center, referral to an emergency department is not recommended (Grade D). 10) Patients with acute ingestions of less than a toxic dose of dimenhydrinate, or chronic exposures to dimenhydrinate and no or mild symptoms, can be observed at home with instructions to call the poison center back if symptoms develop or worsen. The poison center should consider making a follow-up call at approximately 6 hours after ingestion (Grade D). 11) Children less than 6 years of age ingesting at least 7.5 mg/kg of dimenhydrinate should be referred to an emergency department (Grade D). 12) Patients 6 years of age and older ingesting at least 7.5 mg/kg or 300 mg of dimenhydrinate (whichever is less), should be referred to an emergency department for evaluation (Grade D). 13) Following oral exposures of diphenhydramine or dimenhydrinate, do not induce emesis. Because of the potential for diphenhydramine or dimenhydrinate to cause loss of consciousness or seizures, activated charcoal should not be administered en route to an emergency department (Grade D). 14) For chronic dermal exposures of diphenhydramine, skin decontamination (with water or soap and water) should be attempted prior to transporting a patient to an emergency department unless moderate to severe symptoms are already present. In this circumstance, transportation should not be delayed, and EMS personnel should attempt skin decontamination en route to the emergency department (Grade D). 15) Intravenous sodium bicarbonate may be administered by EMS personnel if QRS widening (QRS >0.10 msec) is present and if authorized by EMS medical direction (Grade D). 16) Physostigmine should be reserved for administration in a hospital (Grade D). 17) Benzodiazepines may be administered by EMS personnel if agitation or seizures are present, and if authorized by EMS medical direction (Grade D).

Correlation of Drug Pharmacokinetics and Effectiveness of Multiple-Dose Activated Charcoal Therapy

STUDY OBJECTIVE To evaluate an animal model of multiple-dose activated charcoal (MDAC) therapy and correlate the pharmacokinetic properties of four drugs with the efficacy of MDAC. DESIGN Prospective, randomized, controlled, crossover design. SETTING A university animal research facility. PARTICIPANTS Seven female pigs (15 to 22 kg) with an indwelling central venous line and gastrostomy tube. INTERVENTIONS Acetaminophen (30 mg/kg), digoxin (30 micrograms/kg), theophylline (8.9 mg/kg), and valproic acid (18 mg/kg) were simultaneously administered intravenously over 12 minutes. In the experimental arm, 25 g activated charcoal was administered at 0, 2, 4, 6, 12, 18, 24, and 30 hours through the gastric tube. In the control arm, an equal volume of water was given at the same times. Blood specimens were obtained over 36 hours to measure serum drug concentrations. RESULTS Each drug exhibited enhanced elimination (P < .01) in the MDAC group except valproic acid. Lower intrinsic clearance was correlated (P < .05) with increased systemic elimination during the charcoal arm. Volume of distribution, half-life, and protein binding were not significantly correlated with charcoal-enhanced systemic drug elimination. CONCLUSION The response of a drug to MDAC may be affected by its intrinsic clearance. The restrictive nature of the protein binding of valproic acid may be responsible for its lack of response. Results with the porcine model are consistent with the effects observed in human beings.

Methylene Blue by Intraosseous Infusion for Methemoglobinemia

Intraosseous administration of methylene blue may be an emergency alternative to intravascular administration. A 6-week-old female infant (3 kg) presented to the emergency department after a 1-week illness and appeared cyanotic and listless. Oxygen saturation by oximetry was 86% while the patient was receiving oxygen. Vital signs were blood pressure, 107/80 mm Hg; pulse, 190; respirations, 47; temperature, 39.0 degreesC. A metabolic acidosis and a methemoglobin level of 29.3% were present. After several unsuccessful attempts to establish intravenous access, an intraosseous needle was placed in the infants left tibia. Methylene blue, 1 mg/kg, normal saline solution, and sodium bicarbonate were given intraosseously. The patients oxygen saturation rose to 98% to 100%, and her cyanosis improved. Three hours later, her methemoglobin level was 8.2%. The child recovered uneventfully and was sent home after 3 days. Intraosseous administration of standard intravenous doses of methylene blue rapidly terminated the effects of acquired methemoglobinemia.