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Biomedical subjects

Lewis S Nelson

Publications and source records attributed to Lewis S Nelson.

At least 19 recordsLinked to original sources

Testing positive for methadone and either a tricyclic antidepressant or a benzodiazepine is associated with an accidental overdose death: analysis of medical examiner data.

OBJECTIVES: Patients in emergency departments who use methadone frequently use tricyclic antidepressants (TCAs) and/or benzodiazepines (BZDs). This is a potentially dangerous drug combination. The authors hypothesized that the presence of methadone and a TCA, a BZD, or both is associated with an "accidental" overdose (AOD) death more often than a death from any other cause. METHODS: A retrospective chart review of New York City Office of Chief Medical Examiner data for 2003 was performed. Decedents who tested positive for methadone that were classified as an AOD death, as determined by the medical examiner, were compared with deaths from all other causes for the presence of a TCA, a BZD, or both. A logistical regression was performed to develop a multivariate model identifying additional variables associated with a methadone-positive AOD death. A p-value of <0.05 was considered significant, and 95% confidence intervals (CIs) were calculated. RESULTS: In 2003, there were 5,817 medical examiner cases, of which 500 (8.6%) were methadone positive. Of the methadone-positive cases, 493 were available for analysis; 95 (19.3%) were TCA positive and 158 (32.0%) were BZD positive. The odds of having an AOD death in methadone-positive decedents testing TCA positive, BZD positive, or both were 2.11 (95% CI = 1.32 to 3.37; p < 0.01) for TCAs, 1.66 (95% CI = 1.12 to 2.45; p < 0.02) for BZDs, and 4.34 (95% CI = 1.97 to 9.56; p < 0.001) for both. The multivariate logistic regression of analytes revealed the following covariates associated with an AOD death as well: amitriptyline, cocaine, morphine, or opiates. CONCLUSIONS: Among the methadone-positive cases, testing positive for a TCA, a BZD, or both was associated with an AOD death.

Accidents↗

The availability and use of charcoal hemoperfusion in the treatment of poisoned patients.

BACKGROUND: Charcoal hemoperfusion (CHP) has been one of the preferred methods to enhance the elimination of certain toxins in selected poisoned patients. However, the availability of CHP may be limited because of the expense of cartridges, their narrow indications, and their limited shelf life. Improvements in hemodialysis (HD) technology may contribute to making CHP obsolete. We investigated the availability of CHP in in-hospital HD units at hospitals receiving ambulances dispatched through New York City's emergency response system, hereafter referred to as 911-receiving hospitals, and their recent history of CHP use in poisoned patients. METHODS: The medical directors or managers of all in-hospital HD units in the 911-receiving hospitals of New York City were contacted by E-mail and/or telephone. Participants were administered a standard survey that included questions regarding the availability of CHP cartridges and the date and indication for last CHP use. Participants at institutions that did not stock CHP cartridges were questioned about their opinions on the utility of CHP. RESULTS: Forty-two in-hospital HD units were surveyed, of which 34 (81%) completed the survey. Ten units (29%) had CHP cartridges available for immediate use. Each of these 10 units stocked between 1 and 4 adult-size CHP cartridges, and 1 unit stocked 2 pediatric-size CHP cartridges. Nine units had in-date CHP cartridges, and 1 unit had only expired CHP cartridges. Only 3 units performed CHP in the past 5 years (2 units, theophylline poisonings; 1 unit, aluminum overload). In the 24 units without CHP cartridges, 21 directors believed that most common toxins could be removed effectively through HD and thus CHP rarely was indicated. Only 1 director cited expense as a factor in not stocking CHP cartridges. Two directors reported no specific reason for not stocking the cartridges. CONCLUSION: CHP cartridges are available in only approximately one third of 911-receiving hospitals in New York City. CHP is infrequently performed to enhance toxin elimination in poisoned patients.

Charcoal↗

Renal infarction during the use of rizatriptan and zolmitriptan: two case reports.

Rizatriptan and zolmitriptan are both used to relieve acute migraine and cluster headaches. The mechanism of action is similar to the other triptans, in that they reverse abnormal cerebral vasodilation through their activity as 5-HT1B receptor agonists. Triptan-induced vasoconstriction is attributed to its activity on peripheral 5-HT1B receptors and has rarely been reported to result in stroke, myocardial infarction and ischemic colitis. We present two cases of renal infarction associated with therapeutic triptan use. The first patient is a 57-year-old man with a history of hypertension that was well controlled on valsartan and hydrochlorothiazide. He was recently diagnosed with cluster headaches and was treated with indomethacin, prednisone, butalbital-acetaminophen-caffeine and hydrocodone without relief. He then received two therapeutic doses of rizatriptan on each of the two days prior to presentation. Subsequently, he presented to the emergency department complaining of nausea, vomiting and right-sided abdominal pain. A computerized tomography (CT) scan of the abdomen and pelvis with intravenous contrast revealed a very large wedge shaped infarction of the right kidney. The second patient is a 34-year-old man with a past medical history significant only for life-long migraine headaches successfully treated for the past six years with zolmitriptan. Shortly after taking one therapeutic dose of zolmitriptan, he presented to the emergency department complaining of nausea and left-sided abdominal pain. A CT scan of the abdomen and pelvis with intravenous contrast revealed multiple wedge-shaped infarctions of the left kidney. Renal infarction was confirmed in both patients by arteriogram of the renal arteries. Although both rizatriptan and zolmitriptan are effective in the treatment of migraine and cluster headaches, they may induce peripheral vasospasm leading to renal infarction.

Adult↗

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 panel's 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).

Age Factors↗

Camphor Poisoning: an evidence-based practice guideline for out-of-hospital management.

A review of national poison center data from 1990 through 2003 showed approximately 10,000 annual ingestion exposures to camphor-containing products. A guideline that determines the threshold dose for emergency department referral and need for pre-hospital decontamination could potentially avoid unnecessary emergency department visits, reduce health care costs, optimize patient outcome, 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 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 suspected exposures to camphor-containing products by 1) describing the manner in which an exposure to camphor might be managed, 2) identifying the key decision elements in managing cases of camphor exposure, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This guideline applies to camphor exposure alone. Co-ingestion of additional substances, such as in commercial products of camphor combined with other ingredients, 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 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 recipients of malicious administration of a camphor-containing product should be referred to an emergency department immediately, regardless of the amount ingested (Grade D). 2) Patients who have ingested more than 30 mg/kg of a camphor-containing product or who are exhibiting symptoms of moderate to severe toxicity (e.g., convulsions, lethargy, ataxia, severe nausea and vomiting) by any route of exposure should be referred to an emergency department for observation and treatment (Grade D). 3) Patients exhibiting convulsions following a camphor exposure should be transported to an emergency department by pre-hospital emergency medical care providers (Grade D). A benzodiazepine should be used to control convulsions (Grade C). 4) Patients who have been exposed to a camphor product and who remain asymptomatic after 4 hours can be safely observed at home (Grade C). 5) Induction of emesis with ipecac syrup should not be performed in patients who have ingested camphor products (Grade C). 6) Activated charcoal administration should not be used for the ingestion of camphor products. However, it could be considered if there are other ingredients in the product that are effectively adsorbed by activated charcoal or if other substances have been co-ingested. (Grade C). 7) For asymptomatic patients with topical exposures to camphor products, the skin should be thoroughly washed with soap and water and the patient can be observed at home for development of symptoms (Grade C). 8) For patients with topical splash exposures of camphor to the eye(s), the eye(s) should be irrigated in accordance with usual poison center procedures and that referral take place based on the presence and severity of symptoms (Grade D). 9) Patients with camphor inhalation exposures should be moved to a fresh air environment and referred for medical care based on the presence and severity of symptoms. It is unlikely that symptoms will progress once the patient is removed from the exposure environment (Grade D).

Camphor↗

Massive strontium ferrite ingestion without acute toxicity.

Ingestion of strontium ferrite is previously unreported. We document absorption of strontium without acute toxicity. A 22 year-old schizophrenic man was brought to hospital after he was witnessed to pulverize and ingest flexible adhesive magnets, which later were identified as strontium ferrite. Other than auditory hallucinations his vital signs, physical examination, ECG and routine laboratories were unremarkable. Abdominal radiographs revealed diffuse radiopaque material. He was treated with whole bowel irrigation with polyethylene glycol electrolyte lavage solution (PEG-ELS) until radiographically cleared. His initial blood and urine strontium levels were 2900 microg/l and 15,000 microg/l, respectively (reference range for urine: <240 microg/l, occupational threshold 800 microg/l). A repeat urine level one week later was 370 microg/l. His hospital course was complicated by bacteraemia secondary to a thrombophlebitis at the site of the intravenous catheter, and the patient was treated with intravenous and oral antibiotics. He remained otherwise asymptomatic and was discharged to a psychiatric unit approximately 3 weeks later. Although clearly absorbed, strontium ferrite does not appear to produce acute toxicity. Delayed, and or chronic toxicity cannot be excluded based on this report.

Adult↗

Tiagabine overdose: a case of status epilepticus in a non-epileptic patient.

Tiagabine is an antiepileptic drug used as adjunctive therapy for partial seizures that is believed to selectively inhibit the presynaptic reuptake of gamma aminobutyric acid (GABA). We describe a case of a tiagabine overdose that resulted in status epilepticus (SE) in a patient with no seizure history. A 14-year-old girl with a history of asthma presented with convulsive SE after ingestion of an unknown amount of her sister's tiagabine in a suicide attempt. Attempted anticonvulsant therapy included a total of diazepam 10 mg IV, lorazepam 6 mg IV, pyridoxine 5 g IV, and fosphenytoin 20 mg PE/kg. All were without effect. A computed tomography and electrocardiogram were normal. Continuous bedside EEG monitoring showed suppression of seizure activity following intravenous midazolam. A tiagabine level obtained on ED arrival was 420 ng/mL (therapeutic 20-103 ng/mL). The patient was discharged to psychiatry within 1 week with no neurologic sequelae.

Adolescent↗

Acute vitamin D intoxication in a child.

We present the unique case of a previously healthy, 2-year-old boy with resistant hypercalcemia and hypertension resulting from an unintentional overdose with an imported vitamin D supplement. The patient presented initially to the emergency department with colic and constipation and was discharged after a benign physical examination. The symptoms persisted and, on the second visit, the patient was found to have a serum calcium level of 14.4 mg/dL. Despite therapy with intravenously administered 5% dextrose solution at one-half normal strength, furosemide, calcitonin, and hydrocortisone, the calcium concentration increased to 15.0 mg/dL on the second hospital day and did not decrease until the fourth hospital day, when it fell to 13.9 mg/dL. The vitamin D concentration peaked at 470 ng/mL on hospital day 3. With additional questioning, the mother revealed that she had been giving her son a daily dose of 1 ampule of Raquiferol, an imported vitamin D supplement, instead of the recommended 2 drops per day. Each ampule contained 600,000 IU of vitamin D; therefore, the boy received a total of 2,400,000 IU over 4 days. The patient's hypercalcemia persisted for 14 days and was complicated by persistent hypertension. No renal, cardiac, or neurologic complications were noted. At discharge, the vitamin D concentration was still elevated at 389 ng/mL and the total calcium level had decreased to 11 mg/dL. The boy made a complete clinical recovery. This case highlights the need for caution when using imported and/or unregulated medicines, as well as the dangers of parental dosing errors.

Acute Disease↗

Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine.

In response to concerns regarding the safety of ephedra-containing dietary supplements, manufacturers have marketed "ephedra-free" products. Many of these contain synephrine, a sympathomimetic amine from the plant Citrus aurantium. Synephrine is structurally similar to ephedrine and has vasoconstrictor properties. We describe a 38-year-old patient with ischemic stroke associated with an ephedra-free dietary supplement containing synephrine and caffeine. The patient presented with memory loss and unsteady gait after taking 1 or 2 capsules per day of a dietary supplement (Stacker 2 Ephedra-Free) for 1 week. He had no notable medical history or major atherosclerotic risk factors and took no other medications. Physical examination showed a mildly ataxic gait and substantial Impairment of both concentration and memory. Computed tomography and magnetic resonance Imaging of the brain showed subacute infarctions in the left thalamus and left cerebellum in the distribution of the vertebrobasilar circulation. Other causes of ischemic stroke were evaluated, and findings were unremarkable; a vasospastic origin was considered most likely. The patient was discharged with nearly complete resolution of symptoms. Synephrine, a sympathomimetic amine related to ephedrine, may be associated with Ischemic stroke. Consumers and clinicians need to be Informed about the potential risks of ephedra-free products.

Adult↗

Amiodarone fails to improve survival in amitriptyline-poisoned mice.

OBJECTIVE: Amiodarone, a class III antidysrhythmic agent, blocks Na+, Ca2+, and K+ channels as well as the beta-adrenergic receptor. Despite increased use of amiodarone for wide-complex tachycardia, its efficacy in the treatment of dysrhythmias induced by tricyclic antidepressants has not been tested. We investigated the effect of amiodarone and amitriptyline in a mouse lethality model. METHODS: The LD50 of amitriptyline obtained from reference sources was confirmed by giving 100 mg/kg to 40 mice by intraperitoneal (IP) injection. The safety of the treatment dose of amiodarone was confirmed by giving 50 mg/kg by IP injection to 10 mice. One hundred and nine mice were randomized to receive pretreatment with 50 mg/kg amiodarone (n=55) or an equal volume of saline or water as a volume control (n=54). Thirty minutes after pretreatment or control injection, the mice received amitriptyline, 100 mg/kg. Outcome was defined as death or survival 3 h after amitriptyline injection. RESULTS: In our confirmation of the LD50 of amitriptyline, 25/40 mice died (62.5%). None of the 10 mice that received only amiodarone died. In the control + amitriptyline arm, 36/54 (66.7%) died, compared with 39/55 (70.9%) in the amiodarone+amitriptyline arm (X2, p=0.663). Power analysis demonstrated a 90% chance of finding a 28% difference. CONCLUSIONS: Pretreatment with amiodarone does not appear to significantly alter the lethality of amitriptyline poisoning in mice. Given the inability to monitor cardiac activity in this model, further investigation in a larger animal is required.

Amiodarone↗