Abstract & Commentary
Therapeutic and Toxic Blood Concentrations of Drugs and Other Substances: A Comprehensive New Resource
By David J. Pierson, MD, Editor, Professor Emeritus, Pulmonary and Critical Care Medicine, University of Washington, Seattle, is Editor for Critical Care Alert.
SYNOPSIS: This article, free and available to anyone with Internet access, provides tabulated information on therapeutic, toxic, and potentially fatal blood levels for nearly 1000 drugs and other potentially hazardous substances.
SOURCE: Schulz M, et al. Therapeutic and toxic blood concentrations of nearly 1000 drugs and other xenobiotics. Crit Care 2012; Jul 26;16(4):R136. [Epub ahead of print.]
In this contribution from Germany, Schulz and colleagues provide an annotated, referenced table of therapeutic, toxic, and potentially fatal blood concentrations of nearly 1000 drugs and other xenobiotics (substances foreign to the body that may be ingested or otherwise reach the circulation). The rationale for undertaking this daunting task, as stated by the authors, is the assertion that, "in case of intoxications, the concentration of the ingested substance and/or metabolite in blood plasma better predicts the clinical severity of the case when compared to the assumed amount and time of ingestion. Comparing and contrasting the clinical case against the data provided, including the half-life, may support the decision for or against further intensive care."
Over a period of more than 20 years, the authors accumulated data from original papers, books, and previous smaller compilations, as well as from their own forensic and clinical toxicology laboratory. They included information on more than 170 substances, particularly drugs (both commercially marketed and illicit) introduced since 2003. Blood levels were divided into "therapeutic," levels present when there was evidence that a drug was exerting the sought-after effect; "normal," the levels found for other xenobiotics associated with minimal or no toxic effects; "toxic," the levels obtained when clinically relevant adverse effects were present; and "comatose-fatal," concentrations reported to have caused coma and/or death. No mention is made of attempts to grade the quality of the evidence, nor of any procedures to resolve conflicting reports.
As the authors state, "The compilation includes primarily data for centrally active substances such as hypnotics, sedatives, anxiolytics, antipsychotics, lithium, antidepressants, analgesics, antiepileptics, and stimulants as well as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antihistamines, antibiotics, antimycotics, antiretrovirals, diuretics, ACE-inhibitors, sartanes, beta-blockers, calcium-channel blockers, cardiac glycosides, antiarrhythmics, antiasthmatics, and local anesthetics, among others. In addition and if data were available, other relevant xenobiotics such as controlled substances, illegal and recreational drugs, heavy metals and pesticides, among others were listed. To the best of our knowledge, this compilation is the most current and comprehensive single source of data necessary to support the clinical decision making in case of acute or chronic intoxications with drugs and other xenobiotics."
The article (http://ccforum.com/content/16/4/R136), including its nearly 5-MB supplemental file containing the table, 382 annotations, and 779 references (http://ccforum.com/imedia/2098120449771932/supp1.doc), is available free to anyone in the world with Internet access.
COMMENTARY
The authors of this paper are a pharmacologist and three forensic toxicologists, and it is likely to be an important resource for those fields. However, as impressive as their compilation is, it is likely to be of only limited practical use to emergency physicians and intensivists. This is for two main reasons. First, for most of the included substances, the measurements can be obtained only in specialized and reference laboratories, and these are unlikely to be available quickly enough to be of help during an acute, potentially life-threatening episode. Second, although there are "therapeutic" or "normal" levels listed for most of the substances in the table, many of the "toxic" level spaces are blank, and "comatose-fatal" levels are shown for only a minority of agents. In addition, although data are presented on blood half-life for many substances, most of the levels in the table reflect steady-state measurements, a situation seldom present with acute intoxications and overdoses.
Fortunately, a number of current, evidence-based, and practically useful resources for managing patients with overdoses and toxic exposures are readily available to clinicians — some of them also free, as with the article by Schulz et al. I am grateful to David Carlbom, MD, Director of the University of Washington-Harborview Medical Center Paramedic Training Program, and William Hurley, MD, Medical Director of the Washington Poison Control Center, for assistance with the following recommendations.
My colleagues most often use Micromedex (www.micromedex.com/), UpToDate (www.uptodate.com), and DynaMed (www.dynamed.ebscohost.com), in evaluating and managing patients with known or suspected intoxications. However, these excellent, evidence-based, proprietary resources are expensive for clinicians who are unable to access them through their practice, hospital, or academic institution. Instant access to free, individualized assistance is available 24/7 by calling the Poison Center, at 1-800-222-1222. This national number rings to the caller's nearest regional Poison Center. Dr. Hurley points out that calling the Poison Center also serves a broader public health mission by entering case information into a national database, identifying new trends, and allowing the widest possible sharing of information and experience.
For suspected industrial or environmental exposures, WISER (Wireless Information System for Emergency Responders; http://wiser.nlm.nih.gov/), is a free, public access system developed by the National Library of Medicine, designed to assist first responders in hazardous material incidents. WISER provides a wide range of information on hazardous substances, including substance identification support, physical characteristics, human health information, and containment and suppression advice. WISER is available for download as a stand-alone application on Microsoft Windows PCs, Apple iPhone and iPod Touch, Google Android devices, Windows Mobile devices, BlackBerry devices, Palm OS PDAs, and via WebWISER.
In this contribution from Germany, Schulz and colleagues provide an annotated, referenced table of therapeutic, toxic, and potentially fatal blood concentrations of nearly 1000 drugs and other xenobiotics (substances foreign to the body that may be ingested or otherwise reach the circulation).You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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