Must-read article: America’s Misguided War on Childhood Lead Exposures

Photo: shutterstock/jamie hooper

Very soon, the Centers for Disease Control and Prevention “reference level” for blood lead concentration will be lowered from 5 μg/dL to 3.5 μg/dL. As Charles Schmidt  explains in his superb well-researched article “America’s Misguided War on Childhood Lead Exposures” just published by Undark Magazine, there are several crucially important things to realize about this change:

  1. This impending lowering of the reference lead level is the latest in a long series. The reference level was 40 μg/dL until it was lowered to 10 μg/dL in 1999. The last decree was to 5 μg/dL in 2012.
  2. The reference level is not really a clinical standard or predictor of significant lead toxicity. It is mean to indicate that the child should enter a lead case management program involving, among other things, analysis of the child’s home environment and institution of abatement measures as needed.
  3. At this point the “reference level” is determined by statistics, not clinical evidence. Every 4 years population data is reevaluated, and the level readjusted to the point where 97.5% of children have lead levels below the standard. (Note that a corollary of this procedure is that the more successful we are at lowering lead levels in the population, the lower the reference level will go. At all times, 2.5% of children will be deemed in need of case management. This is truly a toxicological protocol worthy of Sisyphus.)
  4. The lowering of the reference lead level to 3.5 μg/dL will make hundreds of thousands additional children eligible for case management in a system that is already overburdened and under-resourced, without any proof that this change would result in improved health or do anything except alarm families.
  5. Dr. Kim Dietrich — the only person on the CDC’s 16-member expert panel to vote against lowering the reference level — claims in the article that most labs can not accurately measure lead levels as low as 3.5 μg/dL.
  6. Many pediatricians are not well-versed in the nuances of interpreting lead levels, and do not realize that the reference level is a marker of lead exposure, not an indicator of lead toxicity.

This article is essential reading for all pediatricians, emergency practitioners, and toxicologists.

A diagnosis you can’t afford to miss

4 out of 5 stars

Antibody-Mediated Encephalitis. Dalmau J, Graus F. N Engl J Med 2018 Mar 1;378:840-851.

Reference

TPR has posted before about anti-NMDA receptor encephalitis, a must-know, can’t-miss, humbling diagnosis that is distressingly easy to overlook. Although it is not a toxicologic condition, all toxicologists and emergency physicians should be thoroughly familiar with its presentation and clinical course. Let me explain why.

NMDAR encephalitis often begins with behavioral changes, mood swings, and memory deficits in relatively young patients. According to this somewhat technical but excellent review, the median age is 21 years, with a 4:1 ratio of females to males. Because of the initial symptoms, patients are often diagnosed as having new-onset psychiatric disease. It is not unusual for these patients to then be treated with antipsychotic medication in an attempt to control abnormal and agitated behavior.

This is where a toxicologist may be consulted. As the authors point out in this review, patients with NMDAR encephalitis seem to have increased susceptibility to developing neuroleptic malignant syndrome (NMS) after receiving antipsychotics. When these patients then develop movement disorders, autonomic instability, and altered mental status, the toxicology service is brought in to advise about the treatment of NMS.

If the diagnosis of NMDAR encephalitis is not considered, the outcome can be catastrophic. As the authors of this review note “spontaneous clinical improvement is infrequent.” Early treatment with immunotherapy can result in a good outcome. In the case of anti-NMDAR encephalitis, diagnosis is confirmed by finding specific antibodies cerebrospinal fluid. Lumbar puncture is essential, since testing serum for these enzymes yields a false negative in as many as 14% of cases. Optimal treatment has not yet been defined, but current regimens begin with glucocorticoids, IV immune globulin, and plasma exchange transfusion . In resistant cases, medications such as rituximab and cyclophosphamide can be used. It is also critically important to find and remove associated tumors — most commonly teratomas in young women.

This review article is well worth reading, but too detailed and technical to serve as a good introduction to this very important condition. It also covers many other forms of autoimmune encephalitis. Those looking for an introduction to anti-NMDAR encephalitis can consult the following:

One more essential read is Brain on Fire, an account of anti-NMDAR encephalitis from the patient’s point of view. Written by a journalist who was stricken with the condition before much was known about it, the book is so vivid and unforgettable that after reading it you’re unlikely ever to miss the diagnosis again.

Flubromazolam: a potent designer benzodiazepine

Flubromazolam

3 out of 5 stars

Flubromazolam — A new life-threatening designer benzodiazepine. Lukasik-Glebocka M et al. Clin Toxicol 2016;54:66-68.

Abstract

Last month, the Peoria (IL) Journal-Star reported that local police had seized samples of two rarely seen designer sedatives: flubromazolam (alleged street name “liquid Xanax“) and etizolam.

This paper from Poland presents a case report of flubromazolam exposure. A 27-year-old male known to use psychotropic drugs was brought to hospital after being found unconscious at home. On arrival he was comatose with a Glasgow Coma Scale of 3. On exam, he was breathing at rate of 6-8/min and was intubated. He had multiple pressure sores over the right side of his body, as well as hypotonia, hypotension (80/40) and hyporeflexia. He was treated with 1500 ml normal saline. Gelofusine, and pressors. He showed no response to naloxone.

Head CT was unremarkable. Creatine kinase was 15,960 U/L and creatinine 1.53 mg/dL (reference 0.7 – 1.4.) Because the urine drug screen was positive for benzodiazepines, flumazenil was administered in doses 0.5 mg with partial improvement in level of consciousness.

A second head CT on day 3 showed “hypoxic-ischemic changes within the internal capsules bilaterally.” After the patient’s mental status improved and he could provide history, he reported ingesting flubromazolam “3 mg” purchased over the internet. Specific toxicologic testing confirmed the presence of flubromazolam in serum and urine.

The authors suggest that this case indicates that flubromazolam can cause “severe, long-lasting depression of the central nervous system with cardiorespiratory failure, complicated with brain hypoxic-ischemia changes.” Unfortunately, it’s not clear from the paper how thorough the screening was for other drugs such as fentanyl. The key take-home points are that flubromazolam may have extremely potent sedative effects, apparently shows up a benzodiazepine on the urine drug screen and is at least partially reversed by flumazenil.

Etizolam is a short-acting benzodiazepine analog with typical sedative-hypnotic properties. It is used medically in some parts of the world but not approved for use in the United States. Although not scheduled on the federal level, it is restricted in a number of states (AL, AK, GA, VA, FL, IN, MS, TX, LA.) A relatively recent case report indicates that flumazenil may readily reverse the effects of etizolam.