Andrew Stolbach

Clearing the Air: A Review of the Effects of Particulate Matter Air Pollution on Human Health

The World Health Organization estimates that particulate matter (PM) air pollution contributes to approximately 800,000 premature deaths each year, ranking it the 13th leading cause of mortality worldwide. However, many studies show that the relationship is deeper and far more complicated than originally thought. PM is a portion of air pollution that is made up of extremely small particles and liquid droplets containing acids, organic chemicals, metals, and soil or dust particles. PM is categorized by size and continues to be the fraction of air pollution that is most reliably associated with human disease. PM is thought to contribute to cardiovascular and cerebrovascular disease by the mechanisms of systemic inflammation, direct and indirect coagulation activation, and direct translocation into systemic circulation. The data demonstrating PMs effect on the cardiovascular system are strong. Populations subjected to long-term exposure to PM have a significantly higher cardiovascular incident and mortality rate. Short-term acute exposures subtly increase the rate of cardiovascular events within days of a pollution spike. The data are not as strong for PMs effects on cerebrovascular disease, though some data and similar mechanisms suggest a lesser result with smaller amplitude. Respiratory diseases are also exacerbated by exposure to PM. PM causes respiratory morbidity and mortality by creating oxidative stress and inflammation that leads to pulmonary anatomic and physiologic remodeling. The literature shows PM causes worsening respiratory symptoms, more frequent medication use, decreased lung function, recurrent health care utilization, and increased mortality. PM exposure has been shown to have a small but significant adverse effect on cardiovascular, respiratory, and to a lesser extent, cerebrovascular disease. These consistent results are shown by multiple studies with varying populations, protocols, and regions. The data demonstrate a dose-dependent relationship between PM and human disease, and that removal from a PM-rich environment decreases the prevalence of these diseases. While further study is needed to elucidate the effects of composition, chemistry, and the PM effect on susceptible populations, the preponderance of data shows that PM exposure causes a small but significant increase in human morbidity and mortality. Most sources agree on certain “common sense” recommendations, although there are lonely limited data to support them. Indoor PM exposure can be reduced by the usage of air conditioning and particulate filters, decreasing indoor combustion for heating and cooking, and smoking cessation. Susceptible populations, such as the elderly or asthmatics, may benefit from limiting their outdoor activity during peak traffic periods or poor air quality days. These simple changes may benefit individual patients in both short-term symptomatic control and long-term cardiovascular and respiratory complications.

Troponin Elevations Only Detected With a High-sensitivity Assay: Clinical Correlations and Prognostic Significance

OBJECTIVES With clinical use of high-sensitivity troponin I (hsTnI), more frequent troponin elevations will occur. However, the burden and implications of these elevations are not well understood. The authors quantified the prevalence of elevated hsTnI in patients presenting with possible acute coronary syndrome (ACS) who do not have elevated troponin with a current generation assay (cardiac troponin I [cTnI]) and determined the association of these newly detected elevations with a composite of all-cause mortality and subsequent cardiac hospitalization. METHODS This was a prospective observational study of 808 subjects evaluated for possible ACS and followed for up to 1 year. Troponin values were measured with hsTnI (Abbott Laboratories) and cTnI (Abbott and Beckman Coulter). Cardiac hospitalization was defined as hospitalization for ACS, revascularization, acute heart failure (AHF), or tachy/brady arrhythmia that occurred after the index emergency department (ED) visit or hospital discharge. RESULTS Forty subjects (5%) were diagnosed with ACS (26 myocardial infarction and 14 unstable angina). On the initial sample, the prevalence of elevated hsTnI among subjects with nonelevated cTnI was 9.2% using a gender-neutral cutoff (95% confidence interval [CI] = 7.1% to 11.4%) and 11.1% using a gender-specific cutoff (95% CI = 8.8% to 13.4%). Adjudicated diagnoses for subjects whose initial samples had elevated hsTnI but nonelevated cTnI (gender-neutral cutoff) were as follows: three (4.6%) ACS, 15 (23.1%) AHF, three (4.6%) volume overload etiology unclear/noncardiac, three (4.6%) cardiac (non-ACS), and 41 (63.1%) other. Of the 65 patients whose initial samples had hsTnI but nonelevated cTnI, eight developed cTnI elevation on subsequent serial sampling. After traditional cardiovascular risk factors and renal function were adjusted for, subjects with elevated initial hsTnI but nonelevated cTnI (initial and serial sampling) had a higher risk of all-cause mortality and subsequent cardiac hospitalization than subjects with both nonelevated hsTnI and nonelevated cTnI (hazard ratio [HR] = 1.91, 95% CI = 1.14 to 3.19). CONCLUSIONS On the initial sample, 9% to 11% of subjects without cTnI elevation had hsTnI elevation. Although the majority of the patients with these newly detected hsTnI elevations did not have ACS, they had a higher risk for all-cause mortality and subsequent cardiac hospitalization.

Mechanical ventilation was associated with acidemia in a case series of salicylate-poisoned patients.

OBJECTIVES Despite little empiric evidence, mechanical ventilation (MV) in the setting of salicylate poisoning is considered by many to be harmful. When salicylate-poisoned patients are ventilated at conventional settings, the respiratory alkalosis is abolished, more salicylate is able to pass into the central nervous system (CNS), and neurotoxicity worsens. The objective of this study was to identify a relationship between MV, acidosis, and outcome in salicylate-poisoned patients. METHODS The authors electronically searched a poison control center (PCC) database (2001-2007) for patients with salicylate poisoning, defined as a serum concentration > 50 mg/dL, who had MV listed as a therapy. For the 7-year study period, a total of 3,144 salicylate-poisoning cases were identified. Eleven patients met the inclusion criteria of having both salicylate concentrations > 50 mg/dL and required MV; only 7 of them had post-MV data available. RESULTS In all seven patients with post-MV blood gas data, the post-MV pH was < 7.4. In five of six patients with recorded PCO2, the post-MV PCO2 was > 50 mm Hg. Two of the seven patients in the study group died following intubation (two patients died within 3 hours [serum salicylate concentrations, 85 and 79 mg/dL, respectively]). Another patient sustained severe neurologic injury (serum salicylate concentration, 84 mg/dL). The other four patients were ultimately discharged home. In the three patients with the worst clinical outcome, deterioration was reported within hours of intubation. CONCLUSIONS Inadequate MV of patients with salicylate poisoning is associated with respiratory acidosis, acidemia, and clinical deterioration in this series of cases. This supports warnings about the danger of improper MV in patients with salicylate poisoning. A prospective study should be performed.

A report of two deaths from massive ibuprofen ingestion

IntroductionIbuprofen is a commonly used non-steroidal anti-inflammatory drug. While the vast majority of exposures to the drug do not result in significant morbidity, we are reporting 2 fatalities that resulted from massive ibuprofen ingestion.Case 1A 17-year-old girl presented to the emergency department (ED) following an ibuprofen overdose; she was unresponsive with a metabolic acidosis and hypothermic. Her serum ibuprofen concentration was 352 μg/mL: the therapeutic range is 10–50 μg/mL. Despite intensive supportive care and continuous veno-venous hemofiltration, she expired.Case 2A 49-year-old man presents to the ED with a history of divalproex sodium and ibuprofen ingestion. He was unresponsive, hypotensive, and had a significant metabolic acidosis. His serum ibuprofen concentration was 260 μg/mL and serum valproate concentration was 560 μg/mL: the therapeutic range is 50–100 μg/mL. In spite of supportive care and hemodialysis, he expired.DiscussionWe will describe 2 cases of ibuprofen overdose characterized by cardiovascular collapse, acidosis, and hypothermia despite the use of vasopressors and renal replacement therapy. Although rarely reported, massive ibuprofen overdose may result in refractory multisystem organ failure and death.

Dynamic Changes in High-Sensitivity Cardiac Troponin I Are Associated with Dynamic Changes in Sum Absolute QRST Integral on Surface Electrocardiogram in Acute Decompensated Heart Failure

A three‐dimensional electrocardiographic (ECG) metric, the sum absolute QRST integral (SAI QRST), predicts ventricular arrhythmias in heart failure (HF) patients with implantable cardioverter defibrillator and mechanical response to cardiac resynchronization therapy. We hypothesized that there is an association between patient‐specific changes in SAI QRST and myocardial injury as measured by high‐sensitivity troponin I (hsTnI).

ACMT and AACT Position Statement: Preventing Occupational Fentanyl and Fentanyl Analog Exposure to Emergency Responders

To cite this article: Michael J. Moss , Brandon J. Warrick, Lewis S. Nelson, Charles A. McKay, Pierre-André Dubé , Sophie Gosselin , Robert B. Palmer & Andrew I. Stolbach (2017): ACMT and AACT position statement: preventing occupational fentanyl and fentanyl analog exposure to emergency responders, Clinical Toxicology, DOI: 10.1080/15563650.2017.1373782 To link to this article: http://dx.doi.org/10.1080/15563650.2017.1373782

ACMT Position Statement: Determining Brain Death in Adults After Drug Overdose

The position of the American College of Medical Toxicology, endorsed by the American Academy of Clinical Toxicology and the Society of Critical Care Medicine, is as follows: We agree with the American Academy of Neurology (AAN) recommendation that the clinical determination of brain death should only be made in the absence of drug intoxication or poisoning. However, a drug screen and clearance calculation using five drug half-lives (T1/2) are not sufficient to exclude intoxication in all cases. Drug screens are not sufficiently comprehensive to detect all drugs that may cause mental status depression. Even when the specific drugs are quantitatively identified, the use of kinetic data to determine clinical effects is limited because drugs often have prolonged half-lives in overdose. For certain drugs and toxins, the duration of effect may extend beyond their detected presence in the vascular space. We recommend identification of drugs or toxins by careful history and targeted testing. An observation period of longer than five half-lives is appropriate when there is a possibility of an extremely large drug overdose, delayed drug absorption, delayed elimination, or interaction with another agent. In cases where brain death is considered but intoxication is unclear, consultation with a medical toxicologist or clinical toxicologist is recommended to guide decisionmaking regarding the timing or appropriateness of clinical testing, as clinical brain death determination cannot take place until intoxication is excluded. While individual practitioners may differ, these are the positions of the ACMT, AACT, and SCCM at the time written, after a review of the issue and scientific literature. The American Academy of Neurology (AAN) offers guidance for the diagnosis of brain death. Brain death is diagnosed clinically when an irreversible and proximate cause of brain injury is identified and no brain function is present upon clinical assessment [1, 2]. A prerequisite of the practice parameters for clinical testing is the absence of Bdrug intoxication or poisoning.^ The only evidence available regarding brain death determination in the setting of intoxication derives from case reports. To determine the extent to which inaccurate brain death determination by clinical testing may occur in this setting, we conducted a review of the literature inMEDLINE and SCOPUS using the search terms Bbrain death mimic^ and Bbrain death drug overdose^ for the dates January 1, 1960 to June 10, 2015. A total of 1394 titles were reviewed for relevance to the topic, and only ten case reports of brain death mimicry were found (three baclofen [3, 4], two snake bites [5, 6], and one each of valproic acid [7], amitriptyline [8], mixed The intent of this position statement is to reduce the likelihood of erroneous declaration of brain death in the setting of drugor toxininduced coma.

Ethics and Medical Toxicology Research

Optimizing care in medical toxicology necessitates designing and conducting ethical research. Nevertheless, the context of medical toxicology can make clinical research ethically challenging for a variety of reasons: medical toxicology is typified by relative rare conditions; making precise and rapid diagnoses is often fraught with uncertainty; emergent and urgent clinical exigencies make consent difficult or impossible; and some exposures are stigmatized or related to illegal activities that can compromise collecting accurate data from patients. In this paper, we examine some of the ethical issues in medical toxicology research that are especially salient in effort to promote optimal research in the field. The particular issues to be addressed are as follows: (1) rare conditions and orphan agents, (2) randomization and control arms, (3) inclusion and exclusion criteria, (4) outcome measures, (5) consent, (6) confidentiality, (7) registries, (8) oversight, and (9) transparency and reporting. Thinking about these ethical issues prospectively will help researchers and clinicians appropriately navigate them.

The impact of online toxicology training on Fijian emergency doctors’ knowledge: the Global Educational Toxicology Uniting Project (GETUP)

More than one million deaths around the world occur annually because of suicide and accidental poisoning.[1] A significant number of these are attributable to deliberate selfpoisoning. Unfortunately, many physicians worldwide, especially in developing nations, do not have access to formal toxicology training programs.[2] The Global Educational Toxicology Uniting Project (GETUP) was established to help overcome these barriers (www.acmt.net/GETUP.html).[3] Our aim was to investigate whether knowledge of poisoning pathophysiology, risk assessment, and management could be improved by an online toxicology course delivered to emergency doctors in a developing country. We piloted a prospective introductory Internet-based toxicology curriculum delivered to Fijian emergency doctors from the two major Fijian hospital services (Colonial War Memorial Hospital, Suva, Fiji and Lautoka Hospital, Lautoka, Fiji). The 15-module introductory toxicology curriculum was delivered from August to October 2015. The curriculum was adapted from a US-based online course (Physician Education and Assessment Center, Johns Hopkins University, Baltimore, USA) and supplemented with regionally relevant topics (organophosphate and paraquat) adapted from Wikitox. The course required no pre-reading and was structured as series of case-based modules supported by supplied relevant reading material. Doctors participated in a set of preand post-module multiple-choice questions (MCQ) immediately before and after each online case-based module. Pre and post MCQs were not identical, but tested the same educational objectives. The primary outcome was to determine the difference in MCQ score pre and post module for each doctor. Approval to analyze and store the de-identified information was given by the Austin Health Research Ethics Committee, Victoria, Australia. A total of 1280 multiple choice questions were completed by eight emergency doctors and consisted a substantial proportion of medical staff in the emergency training program (8 out of 9, 89%) from these two hospitals. Each doctor completed 80 pre-test and 80 post-test MCQs. The median age of doctors was 30 (IQR 29–35) years old: three were male (37.5%) and five were female (62.5%). Of the emergency residents, four (50%) were current masters of emergency medicine and three (50%) were diploma of emergency medicine students undertaking their degrees through the Fiji National University. Prior to the course, all doctors (100%) identified the lack of toxicology education or services available besides conferences offered through GETUP. Overall, median pre-module MCQ scores improved from 52% (IQR 34,74%) compared to post module MCQ scores 83% (IQR 67,100%) (p< .0001). Across all modules, doctors improved in preand post-test module scores (Table 1). Improving knowledge is one pre-requisite to improving clinical practice. A limitation of this study is that we have not examined whether this training has been retained and translated into practice. In summary, an online toxicology curriculum improved knowledge and had high acceptability in emergency doctors in Fiji. Specific, individualized feedback is immediately available to learners and instructors, who can tailor learning according to their goals and needs. Similar models for toxicology education could benefit other similar contexts, and future inquiries should evaluate the benefits of such courses for emergency medicine practice.

Correction to: ACMT Position Statement: Addressing the Rising Cost of Prescription Antidotes

This article contains a couple typographical errors in the table and in the formatting of references. The authors and the journal apologize for those errors and respectfully include a corrected table and corrected reference list here.