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Journal of Medical Toxicology logoLink to Journal of Medical Toxicology
. 2013 Nov 1;9(4):380–404. doi: 10.1007/s13181-013-0352-5

The Toxicology Investigators Consortium Case Registry—The 2012 Experience

Timothy Wiegand 1,, Paul Wax 2, Eric Smith 2, Katherine Hart 3,4, Jeffrey Brent 5,6
PMCID: PMC3846972  PMID: 24178902

Abstract

In 2010, the American College of Medical Toxicology (ACMT) established its Case Registry, the Toxicology Investigators Consortium (ToxIC). All cases are entered prospectively and include only suspected and confirmed toxic exposures cared for at the bedside by board-certified or board-eligible medical toxicologists at its participating sites. The primary aims of establishing this Registry include the development of a realtime toxico-surveillance system in order to identify and describe current or evolving trends in poisoning and to develop a research tool in toxicology. ToxIC allows for extraction of data from medical records from multiple sites across a national and international network. All cases seen by medical toxicologists at participating institutions were entered into the database. Information characterizing patients entered in 2012 was tabulated and data from the previous years including 2010 and 2011 were included so that cumulative numbers and trends could be described as well. The current report includes data through December 31st, 2012. During 2012, 38 sites with 68 specific institutions contributed a total of 7,269 cases to the Registry. The total number of cases entered into the Registry at the end of 2012 was 17,681. Emergency departments remained the most common source of consultation in 2012, accounting for 61 % of cases. The most common reason for consultation was for pharmaceutical overdose, which occurred in 52 % of patients including intentional (41 %) and unintentional (11 %) exposures. The most common classes of agents were sedative-hypnotics (1,422 entries in 13 % of cases) non-opioid analgesics (1,295 entries in 12 % of cases), opioids (1,086 entries in 10 % of cases) and antidepressants (1,039 entries in 10 % of cases). N-acetylcysteine (NAC) was the most common antidote administered in 2012, as it was in previous years, followed by the opioid antagonist naloxone, sodium bicarbonate, physostigmine and flumazenil. Anti-crotalid Fab fragments were administered in 109 cases or 82 % of cases in which a snake envenomation occurred. There were 57 deaths reported in the Registry in 2012. The most common associated agent alone or in combination was the non-opioid analgesic acetaminophen, being reported in 10 different cases. Other common agents and agent classes involved in death cases included ethanol, opioids, the anti-diabetic agent metformin, sedatives-hypnotics and cardiovascular agents, in particular amlodipine. There were significant trends identified during 2012. Abuse of over-the-counter medications such as dextromethorphan remains prevalent. Cases involving dextromethorphan continued to be reported at frequencies higher than other commonly abused drugs including many stimulants, phencyclidine, synthetic cannabinoids and designer amphetamines such as bath salts. And, while cases involving synthetic cannabinoids and psychoactive bath salts remained relatively constant from 2011 to 2012 several designer amphetamines and novel psychoactive substances were first reported in the Registry in 2012 including the NBOME compounds or “N-bomb” agents. LSD cases also spiked dramatically in 2012 with an 18-fold increase from 2011 although many of these cases are thought to be ultra-potent designer amphetamines misrepresented as “synthetic” LSD. The 2012 Registry included over 400 Adverse Drug Reactions (ADRs) involving 4 % of all Registry cases with 106 agents causing at least 2 ADRs. Additional data including supportive cares, decontamination, and chelating agent use are also included in the 2012 annual report. The Registry remains a valuable toxico-surveillance and research tool. The ToxIC Registry is a unique tool for identifying and characterizing confirmed cases of significant or potential toxicity or complexity to require bedside care by a medical toxicologist.

Keywords: Poisonings, Registry, Overdose, Toxicology, Medical toxicology


The Toxicology Investigators Consortium (ToxIC) case Registry was established in 2010 by the American College of Medical Toxicology (ACMT) as a prospective toxico-surveillance and research tool. Since all cases on the Registry have had formal consultation by a medical toxicologist they represent particularly severe or potentially severe toxicities. A full description of the Registry has been previously published [1]. Participating sites record all cases cared for at the bedside or in a clinic by medical toxicologists. Previous Annual Reports have been published reflecting the 2010 and 2011 data [2, 3].

Several enhancements to the main Registry occurred in 2012 including the integration of new focused data collection sub-registries for prospective multi-site studies. The first sub-registry was developed for patients who ingest caustics and the second for those who have received lipid resuscitation therapy. Also in 2012, a Steering Committee was created with specific goals such as establishing a data entry and collection quality control and assurance program in order to increase the accuracy and fidelity of data collection. Steering Committee members include the Principle Investigators of the Registry along with several medical toxicologists who have been active in case entry, site recruitment and in surveillance since the Registry’s inception.

This is the third annual report and it includes both the 2012 experience and comprehensive and comparative data from the first 2 years of the registry (2010–2011). Registry data is described cumulatively for drug classes and for specific drugs and chemicals within each class as well as compared across time in order to demonstrate trends and for the purpose of surveillance. This report also provides data on toxidromes, supportive care and specific treatments provided during the encounter.

Methods

All participating centers aim to enter all of their medical toxicology consultations into the Registry. Case entry is done online using a password-protected user-friendly interface developed and maintained by ACMT and overseen by the ToxIC Steering Committee. The Registry is Health Insurance Portability and Accountability Act (“HIPAA”) compliant and no patient identifiers are provided on the database. Participation in the Registry is done pursuant to local Institutional Review Board (IRB) policies and procedures as well as the Western Institutional Review Board. Thirty five medical toxicology practices treating patients at 65 institutions distributed throughout the United States plus three international sites contributed cases to the registry in 2012. A list of institutions participating in the Registry during 2012 is provided in Table 1.

Table 1.

Institutions contributing cases to the registry in 2012

USA
 Boston, MA
  Beth Israel Deaconess Medical Center
  Boston Children’s Hospital
 Charlotte, NC
  Carolinas Medical Center
 Chicago, IL
  John H. Stroger, Jr. Hospital of Cook County
 Cincinnati, OH
  Cincinnati Children’s Hospital Medical Center
 Dallas, TX
  Parkland Memorial Hospital
  Children’s Medical Center of Dallas
  UT Southwestern Medical Center
 Denver, CO
  Denver Health
  Porter and Littleton Adventist Hospital
  Swedish Medical Center
  University of Colorado Hospital
 Evanston, IL
  NorthShore University HealthSystem
 Fresno, CA
  UCSF Fresno Medical Center
 Grand Rapids, MI
  Spectrum Health Hospitals
 Harrisburg, PA
  Harrisburg Hospital
 Hartford, CT
  Connecticut Children’s Medical Center
  Hartford Hospital
  U Conn Health Center/John Dempsey Hospital
 Indianapolis, IN
  IU Health University Hospital
  IU Health Methodist Hospital
  Wishard Memorial Hospital
  Riley Hospital for Children
 Kansas City, MO
  Children’s Mercy Hospitals & Clinics
 Long Island, NY
  North Shore University Hospital
  Long Island Jewish Medical Center
 Milwaukee, WI
  Froedtert Hospital
 New York, NY
  Bellevue Hospital Center
  NYU Langone Medical Center
  New York City VA Hospital
  Mount Sinai Hospital
  Staten Island University Hospital
 Newark, NJ
  Newark Beth Israel Medical Center
  University Hospital
 New Brunswick, NJ
  Robert Wood Johnson University Hospital
 Omaha, NE
  University of Nebraska Medical Center
 Philadelphia, PA
  Einstein Medical Center Philadelphia,
  Einstein Medical Center Elkins Park,
  Einstein Medical Center Montgomery
  Hahnemann University Hospital
  Mercy Fitzgerald Hospital
  Mercy Philadelphia Hospital
  St. Christopher’s Hospital for Children
 Phoenix, AZ
  Banner Good Samaritan Medical Center
  Phoenix Children’s Hospital
 Pittsburgh, PA
  UPMC Presbyterian/Shadyside
  UPMC Children’s Hospital of Pittsburgh
 Portland, OR
  Oregon Health and Science University Hospital
  Doernbecher Children’s Hospital
 Richmond, VA
  VCU Medical Center
 Rochester, NY
  Strong Memorial Hospital
  Highland Hospital
  Huther, Doyle
 San Antonio, TX
  San Antonio Military Medical Center
 St Paul, MN
  Regions Hospital
 St Louis, MO
  Barnes Jewish Hospital
 Worcester, MA
  UMass Memorial Medical Center
Non-US sites
 Blacktown, New South Wales, Australia
  Blacktown and Mt. Druitt Hospital
 Haifa, Israel
  Rambam Health Care Campus
 Toronto, Canada
  Sick Children’s Hospital

The information stored on the database includes demographic and detailed clinical data obtained through medical toxicology consultation on the patient’s exposure or encounter including signs, symptoms, clinical course, and treatment. For this report, consultation refers to all patient encounters whether admitted to the medical toxicology service on an inpatient unit or when the toxicologist served as consultant. Outpatient and Emergency Department encounters are also referred to as consultations as long as a formal medical toxicology consultation was done and include documentation in the patients’ record detailing the consultation.

Information about a patient encounter is collected and subsequently entered into the online data interface. Multiple fields are populated for each patient involving check offs or drop-down boxes. There are free text fields for additional information, such as signaling new, unusual or sentinel cases as well as for entry of the substances or species (i.e., envenomation) involved. A data dictionary was added to the 2012 Registry to facilitate accurate collection and naming of specific substances or drugs.

For this report, a search was made of the database assessing the parameters in each field between the data of January 1, 2012 and December 31, 2012. For comparative purposes, and when such data exists, the 2010, 2011, and 2012 as well as cumulative 2010–2012 data are shown.

Results

Total numbers of cases entered include 3,936 in 2010, 6,456 in 2011, and 7,269 in 2012, for a cumulative number of Registry cases of 17,681 by December 31, 2012. The total number of sites actively entering cases in 2012 was 38 which increased from 28 in 2011. Case accrual by month through the end of 2012 is included in Table 2. The mean rate of case accrual in 2012 was 606 cases per month, which is an increase from 539 cases per month in 2011 and 329 cases per month in 2010. The busiest months for consultations in 2012 were in February with 789 consultations and October with 746. Demographic data about patients in the Registry is included in Table 3; in 2012, 67 % of consultations involved patients 19–65 years old, 26 % involved pediatric patients ages 18 years or less and 6 % involved patients aged >65 years old. Forty-nine percent of the consultations involved female patients in 2012. Table 4 shows the referral source for medical toxicology consultations. As shown in Table 4, 61 % of consultations came from the emergency department in 2012 and 12 % were transferred from other hospitals to ToxIC sites.

Table 2.

Number of registry cases enrolled by month

2010 2011 2012 Totals
January 46 442 590 1,078
February 99 505 789 1,393
March 155 775 484 1,414
April 277 617 529 1,423
May 207 323 511 1,041
June 312 501 638 1,451
July 364 684 630 1,678
August 556 573 622 1,751
September 500 430 580 1,510
October 472 636 746 1,854
November 574 478 561 1,613
December 383 503 589 1,475
TOTAL 3,945 6,467 7,269 17,681

Table 3.

Demographics of registry cases

2010 (%) 2011 (%) 2012 (%) Total (%)
Male 1,864 (47) 3,166 (49) 3,741 (51) 8,771 (50)
Female 1,701 (43) 3,301 (51) 3,526 (49) 8,528 (48)
Pregnant 18 (0) 52 (2) 40 (1) 110 (1)
Unspecified 380 (10) 0 (0) 2 (0) 382 (2)
TOTAL 3,945 6,467 7,269 17,691
<2 years 138 (3) 235 (4) 256 (4) 629 (4)
2–6 212 (5) 320 (5) 361 (5) 893 (5)
7–12 100 (3) 124 (2) 156 (2) 380 (2)
13–18 489 (12) 954 (15) 1,069 (15) 2,512 (14)
19–65 2,659 (67) 4,496 (70) 4,904 (67) 12,059 (68)
66–89 183 (5) 338 (5) 404 (6) 925 (5)
>89 years 0 (0) 0 (0) 10 (0) 10 (0)
Unspecified 164 (4) 0 (0) 109 (1) 273 (2)
TOTAL 3,945 6,467 7,269 17,681

Table 4.

Referral sources for medical toxicology consultations

Referral source 2010a (%) 2011b (%) 2012c (%) Total (%)
Emergency department (ED) 2037 (52) 3431 (52) 4423 (61) 10118 (54)
Request from another hospital service (not ED) 399 (10) 1043 (16) 960 (13) 2946 (16)
Outside hospital transfer 522 (13) 804 (12) 867 (12) 2343 (13)
Admitting service 38 (1) 0 (0) 532 (7) 570 (3)
Primary care provider or other outpatientd treating physician 262 (6) 335d (5) 481 (7) 1070 (6)
Poison center 196 (5) 114 (7) 128 (2) 748 (4)
Self-referralf 93 (2) 63 (1) 93 (1) 254 (1)
Employer/independent med eval/workmen’s comp 32 (1) 67 (1) 46 (1) 167 (1)
Other or unknown 412 (10) 7 (0) 8 (0) 427 (2)
Industrial hygienist 2 (0) 0 (0) 0 (0) 2 (0)

aReferral source was documented in 90 % of cases in 2010 some entries had more than one referral source

bReferral source was documented in 85 % of cases in 2011 some entries had more than one referral source

cReferral source was documented in 99 % of cases in 2012 some entries had more than one referral source

dIn 2011 Primary Care Physician category changed to Primary Care Physician/All Outpatient Providers

eIn many cases multiple referral sources were selected

fRefers to self-referral to outpatient clinic

In 2012, 41 % of cases were intentional pharmaceutical exposures, which was the most common reason for the encounter in the Registry. Many cases were coded for more than one reason (e.g. “Intentional Exposure—Pharmaceutical” and “Drug Abuse—Prescription”). Intentional exposures for non-pharmaceuticals were the second most common reason for case encounters (12 %) followed by unintentional exposures with pharmaceuticals (11 %). Drug abuse-related case entries remained a common cause of consultation in 2012 with 10 % of all cases related to illicit drug abuse. Prescription drug abuse accounted for 5 % of cases in 2012 down from 13 % in 2010. All drug and alcohol abuse or drug and alcohol withdrawal-related consultations combined accounted for 27 % of Registry cases in 2012. Table 5 shows the frequency of medical toxicology consultations sorted by the reason a consultation was obtained.

Table 5.

Reasons for medical toxicology consultation

2010 (%) 2011 (%) 2012 (%)
Intentional exposure—pharmaceutical 1,675 (43) 2,499 (39) 3,002 (41)
Intentional exposure—non-pharmaceutical 200 (5) 535 (8) 883 (12)
Unintentional exposure—pharmaceutical 557 (14) 761 (12) 805 (11)
Unintentional exposure—non-pharmaceutical 198 (5) 293 (5) 324 (4)
Drug abuse—illicit/non-prescription drug abuse 521 (13) 348 (5) 708 (10)
Drug abuse—prescription 531 (13) 442 (7) 392 (5)
Drug abuse—over-the-counter (added partway through 2012) NA (0) NA (0) 31 (0)
Ethanol abuse NA (0) 325 (5) 361 (5)
Withdrawal 296 (8) 325 (5) 460 (6)
Adverse drug effect 35 (1) 95 (1) 120 (2)
Adverse drug reaction 116 (3) 229 (4) 371 (5)
Envenomation -total 137 (3) 220 (3) 202 (3)
Envenomation -snake 61 (2) 120 (2) 124 (2)
Envenomation -spider 10 (0) 33 (1) 38 (1)
Envenomation -other 0 (0) 6 (0) 25 (0)
Organ system dysfunction 114 (3) 116 (2) 312 (4)
Interpretation of laboratory data 79 (2) 178 (3) 161 (2)
Occupational evaluation 120 (3) 195 (3) 116 (2)
Environmental evaluation 93 (2) 199 (3) 138 (2)
Case entries per yeara 3,936 6,456 7,269

aThe (%) represents the % of time that a reason for medical toxicology consultation was used out of the total case entries per year not the total number of reasons for medical toxicology consultation. Often case entries included more than one reason for toxicology consultation (i.e., illicit drug abuse and alcohol abuse). The total number of Reasons for consultation in 2012 was 8,573. The percentages thus do not add up to 100 %

Sedative-hypnotics and muscle relaxants with 1,422 exposures (20 % of all 2012 entries) were the most common class of agents responsible for medical toxicology consultation. Clonazepam was the most frequently encountered sedative encountered followed by alprazolam. Sedative-hypnotics and muscle relaxants surpassed non-opioid analgesics (20 %) as the most common class of medications encountered during toxicology consultations in 2012. Exposure rates and Registry entries for different exposure classes are included in Table 6. Opioids (16 %) and antidepressants (15 %) were the third and fourth most common agents described in medical toxicology consultation in 2012.

Table 6.

Agent class involved in consultation

Agent class 2010 N (%) 2011 N (%) 2012 N (%) Total N (%)
Sedative-hypnotics/muscle relaxants 783 (20) 1,492 (23) 1,422 (20) 3,697 (21)
Non-opioid analgesics 854 (22) 1,368 (21) 1,295 (12) 3,517 (20)
Antidepressants 659 (16) 1,029 (16) 1,039 (18) 2,727 (15)
Opioids 619 (17) 1,100 (10) 1,086 (15) 2,805 (16)
Antihistamines and anticholinergics 378 (10) 549 (8) 457 (6) 1,384 (8)
Cardiovascular agents 334 (8) 631 (10) 616 (8) 1,581 (9)
Stimulants and sympathomimetics 247 (6) 774 (12) 692 (10) 1,713 (10)
Psychoactive agents 135 (3) 360 (6) 460 (4) 955 (5)
Ethanol 371 (10) 580 (9) 850 (12) 1,801 (10)
Antipsychotics 366 (9) 587 (9) 551 (8) 1,504 (8)
Lithium 78 (2) 100 (2) 133 (2) 311 (2)
Anticonvulsants and mood stabilizers (non-antipsychotic) 218 (6) 451 (7) 339 (5) 1,008(6)
Caustic agents 45 (1) 93 (1) 47 (1) 185 (1)
Non-ethanol alcohols (toxic, ketones, ethers) 93 (2) 145 (2) 121 (2) 359 (2)
Envenomations 105 (3) 183 (3) 196 (3) 484 (3)
Anti-diabetic 65 (1) 113 (2) 138 (2) 316 (2)
Hydrocarbons 50 (1) 67 (1) 45 (1) 162 (1)
Metal and metalloids 154 (4) 322 (5) 227 (3) 703 (4)
Gases, vapors and irritants 63 (2) 169 (3) 129 (2) 361 (3)
GI 14 (0) 50 (1) 30 (0) 94 (0)
Pulmonary 9 (0) 17 (0) 16 (0) 42 (0)
Endocrine 9 (0) 37 (0) 49 (1) 95 (0)
Chemotherapeutics 5 (0) 20 (0) 12 (0) 37 (0)
Antibiotics, antivirals, antifungals 38 (1) 107 (1) 62 (1) 207 (1)
Herbals, supplements, vitamins 48 (1) 76 (1) 50 (1) 174 (1)
Plants, mushrooms and molds 18 (0) 78 (1) 52 (1) 148 (1)
ADRs NA (0) 593 (6) 405 (6) 998 (5)
Anesthetic agents local and general 16 (0) 21 (0) 30 (0) 67 (0)
WMD, NBC, Radioactive 0 (0) 7 (0) 4 (0) 121(1)
Total agents involved in consultations 5,774 11,119 10,553 27,556

Cases often included more than one agent class in multi-drug exposures thus total number of drugs is more than the total number of cases per year

The % is of the annual number of cases and not of the total agents involved in consultations, i.e., there were 1,422 sedatives reported in 2012 out of a total of 7,296 cases (sedatives were reported in 20 % of all cases)

Table 7 features the major types of toxidromes identified in Registry entries by year. In 2012, specific toxidromes were identified in 22 % of all Registry cases entered. A sedative-hypnotic toxidrome was identified in 40 % of the cases identified as having a toxidrome, the anticholinergic toxidromes was identified in 23 %, a sympathomimetic toxidromes in 13 %, an opioid toxidromes in 13 % and serotonin syndrome was described in 10 % of these cases.

Table 7.

Top types of toxidrome identified

2010 N (%) 2011 N (%) 2012 N (%)
Sedative-hypnotic 327 (44) 653 (38) 621 (40)
Anticholinergic 175 (23) 407 (23) 357 (23)
Sympathomimetic syndrome 73 205 200
73 (10) 205 (12) 200 (13)
Opioid 104 (14) 314 (18) 198 (13)
Serotonin syndrome 54 (14) 147 (8) 163 (10)
Neuroleptic malignant syndrome 9 (1) 7 (0) 17 (1)
Sympatholytic syndrome 0 (0) 2 (0) 6 (0)
Cholinergic 3 (0) 5 (0) 8 (0)
Total cases with toxidromes 745 1,740 1,570

During 2012, patient deaths occurred in 57 cases. This is compared to 35 reported deaths in 2011. The 2010 report did not include fatality data. Table 8 further describes the 2012 fatalities by age, gender, and agents reported in consult. Table 9 compares the frequency of specific agents reported for 2011, 2012 and cumulatively. The most common agent identified either as sole drug or in combination with other agents in 2012 deaths, was the non-opioid analgesic acetaminophen which was reported in ten different cases. The next most frequently cited agent in death cases was ethanol with reported as co-ingestant in five reports followed by amlodipine, gabapentin, and metformin in four cases each. Acetaminophen was reported in three cases as isolated agent and in seven cases along with other agents. Non-opioid analgesics were the most common class of drug cited in death cases. Other common classes included opioids (methadone, hydrocodone, heroin, fentanyl, and tramadol) sedatives (including benzodiazepines, and gabapentin) and cardiovascular medications (amlodipine, digoxin, lisinopril, atenolol, metoprolol, and propranolol). Out of the 57 reported cases, 29 cases involved single drugs, 18 included multiple agents and 10 involved unknown agent or agent combinations.

Table 8.

Deaths reported to the registry 2012

Case # Age Gender Specific agents involved in fatality
Adults 19–65 years of age
 1 60 F Hydrocodone, acetaminophen, tramadol and citalopram
 2 47 F Acetaminophen and ethanol
 3 20 F Acetaminophen
 4 43 F Acetaminophen and carbamazepine
 5 41 F Acetaminophen
 6 61 F Acetaminophen, amitriptyline, gabapentin, citalopram and hydrocodone
 7 62 F Amlodipine and metoprolol
 8 54 M Amlodipine, bupropion, quetiapine, lisinopril and acetaminophen
 9 58 F Acetaminophen, aspirin and lamotrigine
 10 22 M Aspirin and ethanol
 11 19–65 M Non-specified benzodiazepines and opioids
 12 19–65 F Clonazepam
 13 22 M Cocaine and amphetamine
 14 19–65 F Digoxin
 15 48 F Diltiazepam, tramadol, gabapentin and zolpidem
 16 50 F Domperidone
 17 19–65 F Doxepin
 18 30 M Ethanol
 19 36 M Ethylene glycol
 20 32 F Ethanol
 21 36 M Fentanyl patch
 22 61 M Gabapentin, ibuprofen, hydroxyzine and paroxetine
 23 19–65 M Heroin
 24 28 F Hydrocodone and ibuprofen
 25 42 M Hydrogen sulfide
 26 53 F Metformin
 27 55 M Metformin
 28 41 M Methadone
 29 19–65 M Methadone
 30 19–65 M Methadone and ethanol
 31 19–65 M Methanol
 32 51 M Naloxonea
 33 55 F Acetaminophen
 34 20 F Quetiapine
 35 50 F Quetiapine
 36 19–65 F Sulfasalazine
 37 53 F Temazepam and acetaminophen
 38 49 M Cocaine, trazodone, benztropine, lisinopril, amlodipine, and benzonatate
 39 54 M Unknown meds/drugs
 40 60 M Unknown meds/drugs
 41 50 F Unknown meds/drugs
 42 26 M Unknown meds/drugs
Pediatrics (0–18 years)
 43 <2 M Morphine
 44 <2 (21 months) F Unknown meds/drugs
 45 2 to 6 M Unknown meds/drugs
 46 2 to 6 F Unknown meds/drugs
 47 16 F Propranolol
 48 13 to 18 F Unknown meds/drugs
Adults >65 years of age
 49 77 F Valproic acid
 50 >65 M Paraquat
 51 66 F Unknown meds/drugs
 52 66 F Metformin
 53 >65 F Glimepride, warfarin, KCl, atenolol, citalopram, and diazepam
 54 >65 F Bupropion, buspirone, and clonazepam
 55 >65 M Unknown meds/drugs
 56 88 M Insulin
 57 89 M Amlodipine, metformin, and gabapentin

aNaloxone was used in the reversal of an opioid overdose in this case in which a precipitated withdrawal appeared to have caused the death

Table 9.

Registry top causes of death

2011 N 2012 N Total N
Acetaminophen (alone or in formulation) 6 10 16
Alprazolam 1 0 1
Ethanol 0 5 5
Amlodipine 2 4 6
Gabapentin 0 4 4
Metformin 2 4 6
Citalopram 0 3 3
Cyclobenzaprine 1 0 1
Hydrocodone 0 3 3
Methadone 1 3 4
Quetiapine 1 3 4
Aspirin 0 2 2
Bupropion 0 2 2
Clonazepam 0 2 2
Cocaine 0 2 2
Ibuprofen 0 2 2
Lisinopril 0 2 2
Quetiapine 0 2 2
Tramadol 0 2 2
Amitryiptyline 0 1 1
Amphetamine 1 1 2
Atenolol 0 1 1
Benzonatate 0 1 1
Benztropine 0 1 1
Brompheniramine 1 0 1
Bupropion 1 0 1
Buspirone 0 1 1
Carbamazepine 0 1 1
Carbon Monoxide 6 0 6
Clonidine 1 0 1
Codeine 1 0 1
Dextromethorphan 1 0 1
Diazepam 1 1 2
Digoxin 1 1 2
Diltiazem 0 1 1
Diphenhydramine 3 0 3
Domperidone 0 1 1
Doxepin 0 1 1
Ethylene Glycol 1 1 2
Fentanyl (patch) 0 1 1
Glimepride 0 1 1
Guaifenesin 1 0 1
Heroin 3 1 4
Hydrogen sulfide 0 1 1
Hydroxyzine 0 1 1
Insulin 0 1 1
Lamotrigine 2 1 3
Lithium 1 0 1
Melatonin 1 0 1
Methanol 1 1 2
Methylphenidate 1 0 1
Metoprolol 1 1 2
Morphine 1 1 2
Naloxone (precipitated w/d) 0 1 1
Nebivolol 1 0 1
Non–specific benzodiazepine 0 1 1
Non–specific opioid 0 1 1
Oxycodone 5 0 5
Paraquat 0 1 1
Paroxetine 0 1 1
Potassium Chloride (KCl) 0 1 1
Pregabalin 1 0 1
Propranolol 0 1 1
Psychoactive Bath Salts 1 0 1
Sitaglaptin 1 0 1
Sulfasalazine 0 1 1
Temazepam 0 1 1
Trazodone 0 1 1
Valproic acid 0 1 1
Warfarin 0 1 1
Zolpidem 0 1 1
Unknown agent(s) 4 10 14

There were six pediatric fatalities with one in the 13–18 years range with unknown agents ingested and another 16-year-old female ingesting propranolol. There were two death cases in the 2–6-year-old age group with unknown agents involved and two cases reported occurring in children less than 2 years of age. One of these was due to accidental morphine ingestion and the other was from unknown agents. The rest of the fatalities were in adults with 7 involving individuals >65 years old and 44 cases occurring in the 19–65 year-old age range. Fifty-four percent (31 of 57) of fatality cases were in women compared to 2011 where females were reported in just one third (14 of 35) of death cases.

In 2012, intentional exposure to pharmaceutical agents was the most common method of exposure associated with death with 25 reports followed by unintentional exposure to pharmaceuticals with 11. Illicit drug abuse was reported twice and prescription drug abuse was reported three times in the fatality cases. Adverse Drug Reactions resulting in death also occurred; in fact, three out of the four metformin deaths were cited due to adverse drug reactions (ADRs).

Sedative-hypnotic and muscle relaxant agents are shown in Table 10. Agents in these classes involved 13 % of all agents and 20 % of all the cases that were entered into ToxIC in 2012. Benzodiazepines accounted for 54 % of cases in this category. Among the benzodiazepines, the most common was clonazepam, identified in 31 % of all benzodiazepine entries and 17 % of total sedative-hypnotics and muscle relaxants, followed by alprazolam in 26 %, lorazepam in 19 %, and diazepam in 9 % of the benzodiazepine entries for 2012. Zolpidem (8 %) and gabapentin (8 %) were the most common non-benzodiazepine sedative-hypnotic exposure in 2012. Muscle relaxants accounted for 21 % of the cases in this category while within the muscle relaxants group cyclobenzaprine encountered most frequently (45 %) of the muscle relaxants followed by carisoprodol (29 %) and baclofen (18 %).

Table 10.

Sedative-hypnotics/muscle relaxant agents

Agent 2010 N (%) 2011 N (%) 2012 N (%) Total N (%)
Benzodiazepines Clonazepam 180 (21) 262 (18) 242 (17) 684 (18)
Alprazolam 145 (17) 253 (17) 204 (14) 602 (16)
Lorazepam 102 (12) 159 (11) 147 (10) 408 (11)
Diazepam 38 (5) 81 (5) 73 (5) 192 (5)
Unspecified BZDs 0 (0) 62 (4) 59 (4) 121 (3)
Temazepam 17 (2) 34 (2) 27 (2) 78 (2)
Midazolam 3 (0) 10 (1) 5 (0) 18 (0)
Chlordiazepoxide 3 (0) 4 (0) 4 (0) 11 (0)
Triazolam 0 (0) 4 (0) 0 (0) 4 (0)
Chlorazepate 1 (0) 3 (0) 2 (0) 6 (0)
Flurazepam 0 (0) 2 (0) 0 (0) 2 (0)
Brotizolam 0 (0) 1 (0) 1 (0) 2 (0)
Oxazepam 0 (0) 1 (0) 5 (0) 6 (0)
Flunitrazepam 0 (0) 0 (0) 1 (0) 1 (0)
Subtotal–benzodiazepine agents 489 (58) 876 (54) 770 (54) 2135 (57)
Muscle relaxants Cyclobenzaprine 66 (8) 118 (8) 135 (9) 319 (9)
Carisoprodol 48 (6) 94 (6) 88 (6) 230 (6)
Baclofen 25 (3) 43 (3) 53 (4) 121 (3)
Methocarbamol 5 (0) 9 (0) 4 (0) 18 (0)
Metaxalone 0 (0) 5 (0) 6 (0) 11 (0)
Chlorzoxazone 0 (0) 1 (0) 1 (0) 2 (0)
Orphenadrine 2 (0) 0 (0) 1 (0) 3 (0)
Tizanidine 4 (0) 0 (0) 7 (0) 11 (0)
Unknown muscle relaxant 0 (0) 0 (0) 4 (0) 4 (0)
Subtotal—muscle relaxant agents 150 (18) 270 (18) 299 (21) 715 (19)
Barbiturates Butalbital 25 (3) 34 (2) 34 (2) 93 (2)
Phenobarbital 12 (1) 19 (1) 17 (1) 48 (1)
Unknown Barbiturate 0 (0) 6 (0) 5 (0) 11 (0)
Butabarbital 0 (0) 2 (0) 0 (0) 2 (0)
Pentobarbital 0 (0) 1 (0) 0 (0) 1 (0)
Secobarbital 0 (0) 0 (0) 1 (0) 1 (0)
Subtotal–barbiturate agents 37 (4) 65 (4) 57(4) 156 (4)
Z-drugs (non-benzodiazepine GABA-a Agonists) Zolpidem 80 (10) 132 (9) 118 (8) 330 (9)
Eszopiclone 7 (1) 5 (0) 6 (0) 18 (0)
Zaleplon 1 (0) 1 (0) 0 (0) 2 (0)
Zopiclone 10 (1) 1 (0) 6 (0) 17 (0)
Subtotal–z drugs or non-benzodiazepine GABA-A agonists 98 (12) 139 130 (9) 367 (10)
Other sedatives Gabapentin 43 (5) 89 (6) 117 (8) 249 (7)
Pregabalin 11 (1) 15 (1) 19 (1) 45 (1)
Buspirone 5 (1) 32 (2) 25 (2) 62 (2)
Meprobamate 1 (0) 4 (0) 1 (0) 6 (0)
Aminobutyric acid 0 (0) 1 (0) 0 (0) 1 (0)
Chloral hydrate 1 (0) 1 (0) 2 (0) 4 (0)
Dichloralphenazone 1 (0) 0 (0) 1 (0) 2 (0)
Ramelteon 1 (0) 0 (0) 1 (0) 2 (0)
Unknown or other sedatives 0 (0) 3 (0) 0 (0) 1 (0)
Subtotal—other sedative agents 98 (12) 145 (10) 166 (12) 374 (10)
Totals sedative-hypnotics/muscle relaxant agents 837 1,492 1,422 3,751

% is from the total number in the overall agent class unless otherwise noted in the text (i.e., clonazepam is 31 % of all benzodiazepines but 17 % of the total number of sedative-hypnotics and muscle relaxants included in Table 9)

Non-opioid analgesic agents are reported in Table 11. Acetaminophen was again the most common non-opioid analgesic reported in 2012 reported in 67 % of all non-opioid analgesic agent entries. Acetaminophen was reported in 12 % of all Registry cases in 2012. Salicylates (18 %) and non-salicylate non-steroidal anti-inflammatory agents (NSAIDs) made up the rest of this category (15 %). Ibuprofen was the most common NSAID reported (12 %) followed by naproxen (2 %). Aspirin was responsible for nearly all the salicylate entries again in 2012.

Table 11.

Non-opioid analgesics

Agent 2010 N (%) 2011 N (%) 2012 N (%) Total N (%)
Acetaminophen 602 (70) 903 (64) 863 (67) 2368 (66)
NSAIDS Ibuprofen 82 (10) 154 (11) 157 (12) 393 (11)
Naproxen 21 (2) 35 (2.5) 30 (2) 86 (2)
Diclofenac 0 (0) 6 (0) 5 (0) 11 (0)
Unidentified 0 (0) 3 (0) 5 (0) 8 (0)
Celecoxib 0 (0) 3 (0) 0 (0) 3 (0)
Indomethacin 1 (0) 2 (0) 0 (0) 3 (0)
Nabumetone 2 (0) 2 (0) 1 (0) 5 (0)
Ketoprofen 0 (0) 1 (0) 1 (0) 2 (0)
Ketorolac 0 (0) 1 (0) 0 (0) 1 (0)
Meloxicam 0 (0) 1 (0) 1 (0) 2 (0)
Etodolac 2 (0) 0 (0) 2 (0) 4 (0)
Flurbiprofen 1 (0) 0 (0) 0 (0) 1 (0)
Piroxicam 1 (0) 0 (0) 0 (0) 1 (0)
Sulindac 0 (0) 0 (0) 2 (0) 2 (0)
Mefenamic acid 0 (0) 0 (0) 1 (0) 1 (0)
Salicylates Acetylsalicylic acid 137 (15) 247 (17) 192 (15) 576 (16)
Unspecified/other salicylates 0 (0) 60 (4) 35 (3) 95 (3)
Other Ziconotide 1 (0) 3 (0) 0 (0) 4 (0)
Total 850 1,421 1,295 3,566

Table 12 shows the antidepressant agents. The most frequently encountered antidepressant in 2012 was trazodone (15 %) followed by bupropion (15 %), amitriptyline (12 %) and citalopram (12 %). Selective serotonin reuptake inhibitors (SSRIs) were the most common class of antidepressant reported (34 %) followed by tricyclic antidepressants (TCAs) (18 %) and serotonin–norepinephrine reuptake inhibitors (SNRIs) (13 %). Amitriptyline was the most common of the TCAs and venlafaxine was the most common SNRIs (7 %) in 2012.

Table 12.

Antidepressant agents

Agent 2010 N (%) 2011 N (%) 2012 N (%) Total N (%)
SSRIs Citalopram 106 (14) 142 (15) 125 (12) 373 (14)
Escitalopram 23 (3) 38 (3) 46 (4) 107 (4)
Fluoxetine 43 (4) 80 (8) 57 (5) 180 (7)
Paroxetine 35 (5) 32 (4) 27 (3) 94 (3)
Sertraline 47 (4) 67 (7) 85 (8) 199 (7)
Fluvoxamine 2 (0) 6 (1) 4 (0) 12 (0)
Vilazodone 0 (0) 0 (0) 2 (0) 2 (0)
Unspecified SSRI 2 (0) 6 (1) 11 (1) 19 (1)
 Subtotal SSRIs 258 (39) 371 (36) 357 (34) 986 (4)
SNRIs Venlafaxine 37 (5) 84 (8) 72 (7) 193 (7)
Duloxetine 24 (3) 42 (4) 45 (4) 111 (4)
Desvenlafaxine 5 (1) 7 (1) 11 (1) 23 (1)
Milnacipran 0 (0) 1 (0) 2 (0) 3 (0)
 Subtotal SNRIs 66 (10) 134 (13) 130 (13) 330 (12)
Tricyclics Amitriptyline 95 (14) 114 (11) 123 (12) 332 (12)
Nortriptyline 19 (3) 15 (1) 17 (2) 51 (2)
Doxepin 10 (1) 27 (2) 46 (4) 83 (3)
Imipramine 6 (1) 7 (1) 0 (0) 13 (0)
Clomipramine 1 (0) 4 (0) 2 (0) 7 (0)
Unspecified TCA 1 (0) 6 (1) 0 (0) 7 (0)
 Subtotal TCAs 132 (20) 173 (17) 188 (18) 493 (18)
Atypical Bupropion 99 (14) 162 (15) 157 (15) 418 (15)
Mirtazapine 10 (1) 46 (4) 45 (4) 101 (4)
Nefazodone 1 (0) 0 (0) 0 (0) 1 (0)
Trazodone 90 (13) 135 (13) 161 (15) 386 (14)
 Subtotal atypicals 200 (30) 343 (34) 363 (35) 906 (33)
MAOIs Phenelzine 3 (0) 1 (0) 0 (0) 4 (0)
Tranyllcypromine 0 (0) 1 (0) 1 (0) 2 (0)
Subtotal MAOIs 3 (0) 2 (0) 1 (0) 6 (0)
Totals 659 1,023 1,039 2,721

Opioids and opiates accounted for 1,086 entries in 2012 (Table 13). The most common category was the semisynthetic opioid agents with 55 % of all opioid entries. Oxycodone was the most common semisynthetic opioid reported in 2012 accounting for 40 % of all semisynthetic opioids. Oxycodone was also the most common opioid overall in 2012 reported in 22 % of all opioid agent entries. The synthetics, with methadone, tramadol, and fentanyl topping the list, made up 29 % of the opioid agents in 2012. Methadone was the most common synthetic opioid accounting for 14 % of total opioid agent entries and 46 % of all synthetic opioid entries. Tramadol was reported in 10 % of opioid-related entries. Buprenorphine, the partial agonist used in the treatment of opioid-dependence (often simply referred to as Suboxone™ which is the most common formulation containing buprenorphine) was reported in just fewer than 5 % of all opioid entries again in 2012. Heroin use remained high in 2012 with 13 % of cases involving opioid agents due to heroin. There were 137 heroin-related entries in 2012 up from 134 in 2011.

Table 13.

Opioid analgesic agents

Agents 2010 (%) 2011 (%) 2012 (%) Total (%)
Opiates Morphine 37 (5) 56 (5) 69 (6) 162 (6)
Codeine 23 (3) 12 (1) 22 (3) 57 (2)
Opium tincture 0 (0) 1 (0) 1 (0) 2 (0)
Semisynthetic opioids Oxycodone 142 (23) 252 (23) 238 (22) 632 (22)
Hydrocodone 110 (18) 160 (15) 136 (13) 406 (14)
Heroin 61 (10) 134 (12) 137 (13) 332 (12)
Buprenorphine 20 (3) 49 (4) 50 (5) 119 (4)
Hydromorphone 14 (2) 24 (2) 23 (2) 61 (2)
Oxymorphone 2 (0) 11 (1) 10 (1) 23 (1)
Synthetic opioids Methadone 98 (16) 155 (14) 147 (14) 400 (14)
Tramadol 49 (8) 98 (9) 104 (10) 251 (9)
Fentanyl 36 (6) 50 (5) 46 (4) 132 (5)
Propoxyphene 19 (3) 12 (1) 7 (1) 38 (1)
Meperidine 2 (0) 3 (0) 3 (0) 8 (0)
Loperamide 0 (0) 1 (0) 2 (0) 3 (0)
Sufentanil 0 (0) 1 (0) 1 (0) 2 (0)
Tapentadol 1 (0) 1 (0) 7 (1) 9 (0)
Diphenoxylate 1 (0) 0 (0) 0 (0) 1 (0)
Pentazocine 1 (0) 0 (0) 1 (0) 2 (0)
Unspecified opiates 19 (0) 34 (2) 66 (6) 119 (4)
Opioid antagonistsa Naloxone 9 (1) 42 (4) 14 (1) 65 (2)
Naltrexone 0 (0) 4 (0) 2 (0) 6 (0)
Totals 644 1,100 1,086 2,830

aOpioid antagonist when not in use specifically as an antidote (i.e., when used as part of an addiction therapy program such as naltrexone for alcohol or opioid addiction, or when an adverse event occurs during the use of diverted or injected Suboxone™)

Table 14 shows the antihistamine and anticholinergic agents with 457 cases involving agents from this class reported in 2012. Diphenhydramine was the most common antihistamines and anticholinergic agents in 2012 (50 %) followed by hydroxyzine (13 %), benztropine (7 %), and promethazine (7 %).

Table 14.

Antihistamine and anticholinergic agents

Agents 2010 (%) 2011 (%) 2012 (%) Total (%)
Antihistamines Diphenhydramine 234 (65) 299 (60) 229 (50) 762 (58)
Hydroxyzine 34 (9) 62 (12) 59 (13) 155 (12)
Chlorpheniramine 11 (3) 27 (5) 22 (5) 60 (5)
Prochlorperazine 3 (1) 7 (1) 5 (1) 15 (1)
Pyrilamine 1(0) 6 (1) 6 (1) 13 (1)
Cetirizine 3 (1) 5 (1) 6 (1) 14 (1)
Dimenhydrinate 5 (1) 5 (1) 2 (0) 12 (1)
Loratidine 3 (1) 5 (1) 4 (1) 12 (1)
Meclizine 4 (1) 4 (1) 3 (1) 11 (1)
Promethazine 10 (3) 4 (1) 31 (7) 45 (3)
Brompheniramine 0 (0) 3 (1) 3 (1) 6 (0)
Cyproheptadine 1 (0) 3 (1) 9 (2) 13 (1)
Fexofenadine 1 (0) 2 (0) 3 (1) 6 (0)
Pheniramine 11 (3) 2 (0) 1 (0) 14 (1)
Unspecified 1 (0) 23 (5) 18 (4) 42 (3)
Total antihistamines 322 (90) 457 (91) 401 (88) 1180 (90)
Anticholinergic agents Benztropine 21 (6) 21 (4) 30 (7) 72 (5)
Hyoscyamine 3 (1) 7 (1) 5 (1) 15 (1)
Oxybutinin 3 (1) 6 (1) 2 (0) 11 (1)
Tolterodine 0 (0) 4 (1) 0 (0) 4 (0)
Atropine 3 (1) 2 (0) 3 (1) 8 (1)
Donnatol 1 (0) 2 (0) 1 (0) 4 (0)
Scopolamine 2 (0) 2 (0) 3 (1) 7 (1)
Clidinium 0 (0) 1 (0) 0 (0) 1 (0)
Dicyclomine 0 (0) 1 (0) 7 (2) 8 (1)
Fesoterodine 0 (0) 1 (0) 0 (0) 1 (0)
Glycopyrrolate 1 (0) 1 (0) 1 (0) 3 (0)
Trihexyphenidyl 2 (0) 0 (0) 4 (0) 6 (0)
Totals anticholinergic agents 36 (10) 48 (9) 56 (12) 140 (10)
Totals 358 505 457 1,320

Cardiovascular agents are listed in Tables 15 and 16. Antihypertensive agents are included in Table 15 and anticoagulant, antiplatelet and antilipid agents are included in Table 16. The most common categories of cardiovascular agents included the beta blockers (27 %), sympatholytics which were primarily clonidine (19 %), calcium channel antagonists (18 %), cardiac glycosides (9 %) and angiotensin-converting enzyme (ACE) inhibitors (7 %). Propranolol was the most common beta blocker in 2012, accounting for 37 % of all beta blocker entries. Metoprolol (36 %) was reported with nearly the same frequency. The most common sympatholytic was clonidine, which accounted for nearly three quarters (72 %) of the sympatholytic cases. The most common calcium channel antagonist was amlodipine (44 %) followed by diltiazem (27 %) and verapamil (20 %). Digoxin was specified in 98 % of the cardiac glycoside entries and the most common ACE inhibitor reported was lisinopril (87 %). Hydrochlorothiazide was the most common diuretic reported (50 %) followed by furosemide (29 %). Simvastatin was the most common antilipid agent (35 %) and warfarin (67 %) was the most common anticoagulant encountered. Dabigatran was reported in 15 % of anticoagulant entries in 2012.

Table 15.

Cardiovascular agents (% is of each individual agent group (i.e., metoprolol is % of all beta blockers, amlodipine is % of all CCA))

Agent 2010 (%) 2011 (%) 2012 (%) Total (%)
Beta blocker agents Metoprolol 31 (42) 62 (47) 55 (36) 148 (41)
Propranolol 16 (22) 31 (23) 57 (37) 104 (29)
Atenolol 25 (34) 28 (21) 34 (22) 87 (24)
Nebivolol 0 (0) 2 (2) 3 (2) 5 (1)
Nadolol 1 (1) 4 (3) 2 (1) 7 (2)
Betaxolol 1 (1) 2 (2) 0 (0) 3 (1)
Bisoprolol 0 (0) 2 (2) 0 (0) 2 (1)
Sotolol 0 (0) 2 (2) 2 (1) 4 (1)
Unspecified beta blocker 0 (0) 0 (0) 1 (1) 1 (0)
 Total beta blocker agents 74 (24) 133 (23) 154 (27) 361 (25) %Total
Combined alpha-beta blocking agents Carvedilol 10 (91) 16 (73) 22 (69) 48 (74)
Labetolol 1 (9) 6 (27) 10 (31) 17 (26)
 Total combined alpha-beta blocking agents 11 (4) 22 (4) 32 (6) 65 (4) %Total
Calcium channel antagonist agents Amlodipine 27 (47) 47 (40) 45 (44) 119 (43)
Diltiazepam 12 (21) 26 (22) 28 (27) 66 (24)
Verapamil 13 (23) 33 (28) 20 (20) 66 (24)
Nifedipine 4 (7) 9 (8) 8 (8) 21 (8)
Nicardepine 0 (0) 2 (2) 0 (0) 2 (1)
Felodipine 1 (2) 0 (0) 0 (0) 1 (0)
Unspecified calcium channel antagonist 0 (0) 0 (0) 1 (1) 1 (0)
 Total calcium channel antagonists 57 (18) 117 (20) 102 (18) 276 (19) %Total
Cardiac glycosides Digoxin 35 (100) 55 (98) 50 (98) 140 (99)
Digitoxin 0 (0) 1 (1) 0 (0) 1 (0)
Unspecified cardiac glycoside 0 (0) 0 (0) 1 (2) 1 (0)
 Total cardiac glycosides 35 (11) 56 (10) 51 (9) 142 (10) %Total
Ace inhibitor agents Lisinopril 35 (90) 49 (86) 34 (87) 118 (87)
Enalapril 3 (8) 1 (2) 3 (8) 7 (5)
Ramipril 0 (0) 2 (4) 1 (3) 3 (2)
Quinapril 1 (2) 0 (0) 1 (3) 2 (1)
Benazepril 0 (0) 3 (5) 0 (0) 3 (2)
Captopril 0 (0) 1 (2) 0 (0) 1 (1)
Fosinopril 0 (0) 1 (2) 0 (0) 1 (1)
 Total ace inhibiting agents 39 (13) 57 (10) 39 (7) 135 (9) %Total
Angiotensin receptor blockers (ARBs) Valsartan 2 (67) 8 (73) 5 (30) 15 (50)
Losartan 0 (0) 0 (0) 5 (30) 5 (17)
Candesartan 0 (0) 0 (0) 3 (19) 3 (10)
Olmesartan 1 (33) 1 (9) 2 (13) 4 (13)
Irbesartan 0 (0) 1 (9) 1 (6) 2 (7)
Eprosartan 0 (0) 1 (9) 0 (0) 1 (3)
 Total Angiotensin receptor blockers (ARBs) 3 (1) 11 (2) 16 (3) 30 (2) %Total
Vasodilating agents (nitrates and other vasodilators) Hydralazine 1 (25) 3 (30) 7 (54) 11 (41)
Isosorbide 1 (25) 1 (10) 2 (15) 4 (15)
Nitroglycerin 0 (0) 4 (40) 1 (8) 5 (19)
Nitroprusside 1 (25) 1 (10) 1 (8) 3 (11)
Isosorbide mononitrate 0 (0) 0 (0) 0 (0) 0 (0)
Unspecified nitrate 0 (0) 0 (0) 1 (8) 1 (4)
Minoxidil 1 (25) 1 (10) 1 (8) 3 (11)
 Total vasodilating agents 4 (1) 10 (2) 13 (2) 27 (2) %Total
Alpha–1 antagonists Prazosin 2 (33) 3 (27) 5 (25) 10 (27)
Terazosin 0 (0) 3 (27) 4 (20) 7 (19)
Doxazosin 0 (0) 1 (91) 4 (20) 5 (14)
Alfuzosin 1 (17) 0 (0) 0 (0) 1 (3)
Tamsulosin 3 (50) 4 (36) 7 (35) 14 (38)
 Total alpha-1 antagonists 6 (2) 11 (2) 20 (4) 37 (3) %Total
Sympatholytics Clonidine 63 (90) 93 (85) 81 (76) 237 (83)
Guanfacine 7 (10) 17 (15) 24 (23) 48 (17)
Dexmedetomidine 0 (0) 0 (0) 1 (1) 1 (0)
 Total sympatholytics 70 (23) 110 (19) 106 (19) 286 (20) %Total
Antiarrhythmics Amiodarone 1 (100) 0 (0) 1 (17) 2 (14)
Dofetilide 0 (0) 1 (14) 1 (17) 2 (14)
Flecainide 0 (0) 2 (29) 2 (33) 4 (29)
Propafenone 0 (0) 1 (14) 0 (0) 1 (7)
Quinidine 0 (0) 1 (14) 0 (0) 1 (7)
Sotolol 0 (0) 2 (29) 2 (33) 4 (29)
 Total antiarrhythmics 1 (0) 7 (1) 6 (1) 14 (1) %Total
Diuretics Hydrochlorothiazide 8 (73) 25 (61) 12 (50) 45 (59)
Furosemide 0 (0) 8 (20) 7 (29) 15 (20)
Acetazolamide 1 (9) 0 (0) 2 (8) 3 (4)
Chlorothalidone 0 (0) 1 (2) 2 (8) 3 (4)
Spironolactone 0 (0) 3 (7) 1 (4) 4 (5)
Torsemide 1 (9) 1 (2) 0 (0) 2 (3)
Triamterene 1 (9) 3 (7) 0 (0) 4 (5)
 Total diuretics 11 (4) 41 (7) 24 (4) 76 (5) %Total
Totals all Antihypertensives + arrhythmics 311 575 563 1,449

Table 16.

Cardiovascular agents II—antilipid, anticoagulant, antiplatelet

Agent type Agent 2010 (%) 2011 (%) 2012 (%) Total (%)
Anticoagulant Warfarin 11 (92) 25 (47) 22 (67) 58 (43)
Dabigatran 0 (0) 1 (3) 5 (15) 6 (4)
Enoxaparin 1 (8) 1 (3) 2 (6) 4 (3)
Dalteparin 0 (0) 0 (0) 2 (6) 2 (1)
Fondaparinux 0 (0) 2 (6) 0 (0) 2 (1)
Rivaroxaban 0 (0) 0 (0) 2 (6) 2 (1)
Unspecified anticoagulants 0 (0) 1 (3) 0 (0) 1 (1)
Total anticoagulants 12 (55) 30 (50) 33 (62) 75 (55) % of total
Antiplatelets Argatroban 0 (0) 1 (2) 0 (0) 1 (1)
Clopidogrel 0 (0) 4 (7) 3 (10) 7 (87)
Total antiplatelets 0 (0) 5 (8) 3 (6) 8 (6) % of total
Antilipids Simvastatin 5 (23) 14 (23) 6 (11) 25 (47)
Lovastatin 0 (0) 3 (2) 1 (2) 4 (3)
Atorvastatin 1 (5) 3 (2) 3 (6) 7 (5)
Pravastatin 1 (5) 1 (1) 1 (2) 3 (2)
Rosuvastatin 1 (5) 2 (2) 2 (4) 5 (4)
Ezetimibe 0 (0) 1 (1) 0 (0) 1 (1)
Fenofibrate 1 (5) 1 (1) 3 (6) 5 (4)
Gemfibrozil 1 (5) 1 (1) 1 (2) 3 (2)
Total antilipids 10 (45) 26 (43) 17 (32) 53 (39) % of total
Total antilipid, anticoagulant, antiplatelet–CV agents B 22 61 53 136

Table 17 shows agents reported as stimulants and sympathomimetics. While there had been a large increase in these agents from 2010 to 2011 the 2012 data remained stable compared to 2011. Amphetamines and stimulant-type attention-deficit hyperactivity disorder (ADHD) disorder type medications as well as designer amphetamines including mephedrone, methylenedioxypyrovalerone (MDPV) and other amphetamines often referred to as “psychoactive bath salts” are included in Table 17. Cocaine remains the most common stimulant reported in 2012 (32 %) followed by methamphetamine (11 %), amphetamine (11 %), caffeine (10 %), and methylphenidate (8 %). Psychoactive bath salts and designer amphetamines represented 6 % of the stimulant entries with methylenedioxymethylamphetamine (MDMA) being the most common (4 %) followed by mephedrone (2 %). “Other” designer amphetamines and psychoactive bath salts (including unidentified recreational stimulants identified as bath salts) accounted for 6 % of all stimulant cases.

Table 17.

Stimulant and sympathomimetic agents

Agent 2010 (%) 2011 (%) 2012 (%) Total (%)
Amphetamine derivatives Amphetamine 40 (13) 141 (18) 73 (11) 254 (14)
Methamphetamine 38 (13) 70 (9) 74 (11) 182 (10)
Dextroamphetamine 26 (9) 35 (6) 43 (6) 104 (6)
Lisdexamfetamine 6 (2) 12 (2) 12 (2) 30 (2)
Pseudoephedrine 7 (2) 10 (2) 13 (2) 30 (2)
Ephedrine 0 (0) 1 (0) 2 (0) 3 (0)
Phenylephrine 4 (1) 14 (2) 9 (1) 27 (2)
Benzphetamine 0 (0) 0 (0) 1 (0) 1 (0)
Psychoactive bath salts and designer amphetamines MDPV 0 (0) 14 (2) 4 (1) 18 (1)
Mephedrone 1 (0) 49 (6) 16 (2) 66 (4)
MDMA 12 (4) 14 (2) 30 (4) 56 (3)
MDE 0 (0) 0 (0) 1 (0) 1 (0)
2CI (2,5-dimethoxy-4–iodophenethylamine) 0 (0) 0 (0) 1 (0) 1 (0)
MEC 0 (0) 0 (0) 1 (0) 1 (0)
Desoxypipradol 0 (0) 1 (0) 0 (0) 1 (0)
Alpha-pyrrolidinovalerophenone 1 (0) 0 (0) 4 (1) 5 (0)
NBOME compounds 0 (0) 0 (0) 1 (0) 1 (0)
 Other bath salt, cathinone, designer stimulant Other 2 (1) 40 (5) 44 (6) 86 (5)
Other stimulants Cocaine 102 (33) 237 (31) 221 (32) 560 (32)
Caffeine 31 (11) 67 (9) 66 (10) 164 (9)
Methylphenidate 24 (8) 34 (4) 52 (8) 110 (6)
Atomoxetine 2 (1) 6 (1) 14 (2) 22 (1)
Dexmethylphenidate 2 (1) 3 (0) 4 (1) 9 (1)
Phentermine 2 (1) 2 (0) 2 (0) 6 (0)
Ethylphenidate 0 (0) 1 (0) 0 (0) 1 (0)
Isometheptene 1 (0) 1 (0) 1 (0) 3 (0)
Modafinil 1 (0) 3 (0) 1 (0) 5 (0)
Methylhexanamine 0 (0) 2 (0) 0 (0) 2 (0)
Unspecified stimulant 0 (0) 4 (1) 2 (0) 6 (0)
Totals all stimulant agents 302 761 692 1,755

Agents classified as psychoactive drugs are included in Table 18. In 2012, marijuana and dextromethorphan were both reported in 29 % of the entries with psychoactive agents reported. Synthetic cannabinoid use (i.e., K2 or Spice) remained flat and was reported in 11 % of all cases involving psychoactive agents. While an overall small number LSD cases were reported (18 times in 2012 accounting for 4 % of psychoactive agent entries) this is markedly up from a single entry for LSD in 2011. Phencyclidine was reported in 95 entries (21 %) up from 57 (16 %) the previous year.

Table 18.

Psychoactive agents including dextromethorphan. Cannabinoids (THC and synthetics), DXM, GHB, dissociatives, and hallucinogens

Agent 2010 (%) 2011 (%) 2012 (%) Total (%)
Cannabinoids Marijuana or other cannabis product 27 (20) 123 (34) 135 (29) 285 (30)
Synthetic (K2) 11 (8) 40 (11) 50 (11) 101 (11)
Pharmaceutical THC (i.e., dronabinol) 0 (0) 1 (0) 2 (0) 3 (0)
Dissociatives Dextromethorphan 65 (46) 120 (34) 132 (29) 317 (33)
Phencyclidine (PCP) 22 (16) 57 (16) 95 (21) 174 (18)
Ketamine 1 (0) 2 (0) 4 (1) 7 (1)
Methoxetamine 0 (0) 0 (0) 2 (2) 2 (0)
Hallucinogens LSD 6 (1) 4 (1) 18 (4) 28 (3)
Dimethyltryptamine or other tryptamines 0 (0) 1 (0) 6 (1) 7 (1)
Gammhydroxybutyrate (GHB) and related agents GHB 0 (0) 4 (1) 10 (2) 14 (1)
1,4 BD 1 (0) 1 (0) 0 (0) 2 (0)
GBL 1 (0) 0 (0) 1 (0) 2 (0)
Other psychoactive agents Ibogain 0 (0) 0 (0) 1 (0) 1 (0)
Salvia divinorum 0 (0) 4 (1) 1 (0) 5 (1)
Psychoactive plants ingested recreationally Argyreia nervosa (Hawaiian baby woodrose seeds) 0 (0) 0 (0) 1 (0) 1 (0)
Datura stramonium (jimson weed) 1 (0) 0 (0) 2 (0) 3 (0)
Totals all psychoactives 135 357 460 952

Table 19 shows the number of cases involving ethanol. Cases involving ethanol increased from 2011 to 2012. Ethanol was reported 850 times in 2012 up from 580 in 2011.

Table 19.

Ethanol

Agent 2010 2011 2012 Total
Ethanol and alcoholic beverages 371 580 850 1,801

Table 20 shows the antipsychotic agent exposures. The atypical antipsychotics were the most common type of antipsychotic reported with 88 % of all antipsychotic entries involving atypical agents. Quetiapine was the most common atypical antipsychotic reported (48 %) followed by risperidone (13 %), olanzapine (11 %), and aripiprazole (9 %). Haloperidol was reported in 6 % of antipsychotic entries. The most common phenothiazine reported was chlorpromazine (3 %).

Table 20.

Antipsychotic agents

Agent 2010 (%) 2011 (%) 2012 (%) Total (%)
Atypical Quetiapine 178 (49) 260 (44) 263 (48) 701 (46)
Risperidone 43 (12) 72 (12) 73 (13) 188 (12)
Olanzapine 37 (10) 69 (12) 63 (11) 169 (11)
Aripiprazole 23 (6) 63 (11) 50 (9) 136 (9)
Ziprasidone 17 (5) 28 (5) 24 (4) 69 (5)
Clozapine 13 (4) 21 (3) 10 (2) 44 (3)
Paliperidone 0 (0) 3 (0) 0 (0) 3 (0)
Asenapine 1 (0) 2 (0) 0 (0) 3 (0)
Iloperidone 1 (0) 0 (0) 0 (0) 1 (0)
Total atypical antipsychotics 313 (84) 518 (87) 483 (88) 1,314 (87)
Phenothiazines and other 1st generation Chlorpromazine 11 (3) 14 (2) 16 (3) 41 (3)
Perphenazine 6 (2) 7 (1) 7 (1) 20 (1)
Prochlorperazine 3 (1) 6 (1) 5 (1) 14 (1)
Thioridazine 2 (0) 1 (0) 0 (0) 3 (0)
Loxapine 2 (0) 5 (1) 6 (1) 13 (1)
Thiothixene 0 (0) 3 (0) 1 (0) 4 (0)
Fluphenazine 2 (0) 1 (0) 2 (0) 5 (0)
Pericyazine 2 (0) 1 (0) 0 (0) 3 (0)
Pimozide 0 (0) 1 (0) 0 (0) 1 (0)
Total phenothiazines and other 1st gen 28 (8) 39 (7) 37 (7) 104 (7)
Butyrophenones Haloperidol 30 (8) 36 (6) 31 (6) 97 (6)
Totals 371 593 551 1,515

Lithium was listed separately from the antipsychotics and anticonvulsant mood stabilizers in Table 21. Lithium was reported 133 times in 2012 up from 100 the previous year.

Table 21.

Lithium

Agent 2010 2011 20 12 Total
Lithium 78 100 133 311

Table 22 includes the anticonvulsant and non-antipsychotic mood stabilizing agents (excluding lithium). Valproic acid (28 %) followed by lamotrigine (27 %) were the most common two agents from this class in 2012. Lamotrigine increased accounting for 27 % of reports involving anticonvulsants and non-antipsychotic mood stabilizing agents in 2012 up from 19 % in 2011. Phenytoin was encountered much less frequently in 2012 making up 11 % of entries in 2012 down from 25 % in 2011.

Table 22.

Anticonvulsant agents and mood stabilizers (non lithium or antipsychotic)

Agent 2010 (%) 2011 (%) 2012 (%) Total (%)
Valproic acid 46 (28) 86 (25) 96 (28) 228 (27)
Lamotrigine 35 (21) 65 (19) 92 (27) 192 (23)
Carbamazepine 25 (15) 38 (11) 49 (14) 112 (13)
Phenytoin 23 (14) 88 (25) 37 (11) 148 (17)
Fosphenytoin 1 (0) 0 (0) 1 (0) 2 (0)
Topiramate 19 (12) 32 (9) 29 (9) 80 (9)
Oxcarbazepine 9 (5) 26 (7) 17 (5) 52 (6)
Levetiracetam 2 (0) 6 (0) 8 (2) 16 (2)
Felbamate 1 (0) 1 (0) 0 (0) 2 (0)
Lacosamide 1 (0) 1 (0) 2 (0) 4 (0)
Primidone 1 (0) 2 (0) 5 (1) 8 (1)
Tiagabine 1 (0) 1 (0) 2 (0) 4 (0)
Zonisamide 1 (0) 1 (0) 1 (0) 3 (0)
Totals 165 347 339 851

Table 23 includes the gastrointestinal (GI) agents. Omeprazole (25 %) followed by ondansetron (18 %) were the two most common GI agents reported in 2012.

Table 23.

GI agents including antacids, PPIs, other GI

Agent 2010 (%) 2011 (%) 2012 (%) Total (%)
Proton pump inhibitors (PPIs) and antacids Omeprazole 3 (25) 9 (19) 7 (25) 19 (21)
Esomeprazole 1 (8) 2 (4) 0 (0) 2 (2)
Lansoprazole 0 (0) 2 (4) 0 (0) 2 (2)
Pantoprazole 0 (0) 1 (2) 2 (7) 3 (3)
Ranitidine 2 (17) 9 (19) 1 (4) 12 (13)
Famotidine 0 (0) 3 (6) 2 (7) 5 (6)
Other agents (promotility, antiemetic) Metoclopramide 2 (17) 6 (13) 2 (7) 10 (11)
Domperidone 0 (0) 0 (0) 1 (4) 1 (1)
Ondansetron 2 (17) 4 (8) 5 (18) 11 (12)
Dicyclomine 1 (8) 3 (6) 1 (4) 5 (6)
Bismuth subsalicylate 0 (0) 2 (4) 2 (7) 4 (5)
Docusate 1 (8) 2 (4) 1 (4) 4 (5)
Polyethylene glycol 0 (0) 2 (4) 1 (4) 3 (3)
Simethicone 0 (0) 1 (2) 1 (4) 2 (2)
Drotaverine 0 (0) 0 (0) 1 (4) 1 (1)
Sucralfate 0 (0) 1 (2) 0 (0) 1 (1)
Sulfasalazine 0 (0) 1 (2) 1 (4) 2 (2)
Senna 0 (0) 3 (6) 2 (8) 5 (6)
Total GI agents 12 54 30 96

Anti-diabetic agents are shown in Table 24 with sulfonylureas (28 %), metformin (28 %), and insulins (19 %) the most frequent types of anti-diabetic agents reported.

Table 24.

Diabetic agents

Agent type Agent 2010 (%) 2011 (%) 2012 (%) Total (%)
Biguanides Metformin 22 (34) 29 (26) 41 (28) 92 (29)
Insulins Insulins 16 (25) 35 (31) 41 (28) 92 (29)
Sulfonylureas Glyburide 10 (15) 20 (18) 26 (19) 56 (18)
Glipizide 7 (11) 14 (13) 22 (16) 43 (14)
Glimepiride 8 (12) 6 (5) 7 (5) 21 (7)
Tolbutamide 0 (0) 1 (1) 0 (0) 1 (0)
Unspecified sulfonylurea 0 (0) 1 (1) 0 (0) 1 (0)
Other agents Pioglitazone 1 (2) 3 (3) 0 (0) 4 (1)
Nateglinide 0 (0) 2 (2) 0 (0) 2 (0)
Sitagliptin 0 (0) 1 (1) 1 (1) 2 (0)
Liraglutide 1 (2) 0 (0) 0 (0) 1 (0)
Totals 65 112 138 315

Guaifenesin (38 %) followed by albuterol (25 %) were the most common pulmonary agents reported in 2012 described in Table 25. Endocrine agents are described in Table 26, chemotherapeutic agents in Table 27 and antibiotics in Table 28. Anesthetic agents including local and general anesthetics are included in Table 29.

Table 25.

Pulmonary agents, decongestants and mucolytics

Agent 2010 (%) 2011 (%) 2012 (%) Total (%)
Guaifenesin 6 (33) 8 (30) 6 (38) 20 (34)
Albuterol 1 (6) 4 (15) 4 (25) 9 (15)
Theophylline 2 (11) 2 (7) 1 (6) 5 (8)
Diphylline 0 (0) 1 (4) 0 (0) 1 (2)
Montelukast 0 (0) 1 (4) 1 (6) 2 (3)
Terbutaline 0 (0) 1 (4) 0 (0) 1 (2)
Benzonatate 2 (11) 4 (15) 1 (6) 7 (11)
Tetrahydrozoline 3 (17) 2 (7) 0 (0) 5 (8)
Oxymetazoline 0 (0) 1 (4) 0 (0) 1 (2)
Unspecified 4 (22) 3 (11) 3 (19) 10 (16)
Totals 18 27 16 61

Table 26.

Endocrine agents—non-diabetic

Agent 2010 N (%) 2011 N (%) 2012 N (%) Total N (%)
Levothyroxine and thyroxine 3 (21) 15 (41) 32 (65) 50 (50)
Prednisone 3 (21) 8 (17) 7 (14) 18 (18)
Desmopressin 1 (7) 2 (4) 1 (2) 4 (4)
Finasteride 0 (0) 2 (4) 0 (0) 2 (2)
Anabolic steroids 0 (0) 1 (2) 2 (4) 3 (3)
Estrogens 3 (21) 0 (0) 3 (6) 6 (6)
Calcitonin 0 (0) 1 (2) 0 (0) 1 (1)
Fludricortisone 0 (0) 1 (2) 0 (0) 1 (1)
Hydrocortisone 0 (0) 1 (2) 1 (2) 2 (2)
Glucagon-like-peptide 1 0 (0) 1 (2) 0 (0) 1 (1)
Methimazole 0 (0) 1 (2) 0 (0) 1 (1)
Methylprednisolone 1 (7) 1 (2) 1 (2) 3 (3)
Progesterone 1 (7) 1 (2) 1 (2) 3 (3)
Triiodothyronine 0 (0) 1 (2) 1 (2) 2 (2)
Other thyroid hormone product 0 (0) 1 (2) 0 (0) 1 (1)
Totals 14 37 49 100

Table 27.

Chemotherapeutic agents

Agent 2010 N (%) 2011 N (%) 2012 N (%) Total N (%)
Cyclosporine 2 (22) 3 (15) 0 (0) 5 (12)
Colchicine 3 (33) 7 (35) 1 (8) 11 (27)
Interferon alpha 1 (11) 2 (10) 0 (0) 3 (7)
Methotrexate 0 (0) 2 (10) 6 (50) 8 (20)
Sirolimus 2 (22) 2 (10) 0 (0) 4 (10)
Sorafenib 0 (0) 1 (5) 0 (0) 1 (2)
Tacrolimus 0 (0) 1 (5) 2 (17) 3 (7)
Tamoxifen 0 (0) 1 (5) 1 (8) 2 (5)
Topetecan 0 (0) 1 (5) 0 (0) 1 (2)
Azathioprine 1 (11) 0 (0) 0 (0) 1 (2)
Doxorubicin 0 (0) 0 (0) 1 (8) 1 (2)
Ifosfamide 0 (0) 0 (0) 1 (8) 1 (2)
Total 9 20 12 41

Table 28.

Antimicrobials (antibiotics, antivirals, antifungals)

Agent 2010 N (%) 2011 N (%) 2012 N (%) Total N (%)
Abacavir 0 (0) 2 (2) 1 (2) 3 (1)
Acyclovir 1 (3) 1 (1) 1 (2) 3 (1)
Amantadine 1 (3) 3 (3) 4 (7) 8 (4)
Amoxicillin 0 (0) 7 (7) 4 (7) 11 (5)
Atazanavir 0 (0) 1 (1) 1 (2) 2 (1)
Azithromycin 0 (0) 2 (2) 4 (7) 6 (3)
Cefepime 0 (0) 0 (0) 1 (2) 1 (0)
Ceftriaxone 1 (3) 1 (1) 0 (0) 2 (1)
Cephelexin 3 (8) 5 (5) 1 (2) 9 (4)
Ciprofloxaxin 1 (3) 2 (2) 3 (5) 6 (3)
Clarithromycin 0 (0) 0 (0) 1 (2) 1 (0)
Clindamycin 0 (0) 6 (6) 2 (3) 8 (4)
Dapsone 0 (0) 3 (3) 3 (5) 6 (3)
Darunavir 0 (0) 1 (1) 0 (0) 2 (1)
Doxycycline 2 (5) 1 (1) 0 (0) 3 (1)
Efavirenz 0 (0) 2 (2) 0 (0) 2 (1)
Emtricitabine 0 (0) 3 (3) 1 (2) 4 (2)
Erythromycin 1 (3) 2 (2) 0 (0) 3 (1)
Fluconazole 0 (0) 0 (0) 1 (2) 1 (1)
Isoniazid 11 (28) 7 (7) 6 (10) 24 (12)
Lamivudine 0 (0) 1 (0) 2 (3) 3 (1)
Levofloxacin 0 (0) 1 (1) 1 (2) 2 (1)
Linezolid 2 (5) 2 (2) 0 (0) 2 (1)
Maraviroc 0 (0) 1 (1) 0 (0) 1 (1)
Metronidazole 2 (5) 5 (5) 2 (3) 9 (4)
Minocycline 0 (0) 2 (2) 0 (0) 2 (1)
Moxifloxacin 0 (0) 1 (1) 1 (2) 2 (1)
Nafcillin 0 (0) 1 (1) 0 (0) 1 (1)
Nevirapine 0 (0) 1 (1) 1 (2) 2 (1)
Nitrofurantoin 0 (0) 1 (1) 1 (2) 2 (1)
Penicillin 2 (5) 2 (2) 0 (0) 4 (2)
Piperacillin 0 (0) 2 (2) 0 (0) 2 (1)
Raltegravir 0 (0) 1 (1) 1 (2) 2 (1)
Ribavirin 0 (0) 1 (1) 1 (2) 2 (1)
Rifampin 0 (0) 0 (0) 1 (0) 1 (1)
Ritonavir 2 (5) 3 (3) 2 (3) 7 (3)
Sulfamethoxazole 3 (8) 14 (13) 4 (7) 21 (10)
Tazobactam 0 (0) 1 (1) 0 (0) 1 (0)
Tenofovir 0 (0) 0 (0) 1 (2) 1 (0)
Tetracycline 3 (8) 0 (0) 2 (3) 5 (2)
Trimethoprim-sulfamethoxazole 4 (10) 12 (11) 4 (7) 20 (10)
Vancomycin 1 (3) 1 (1) 4 (7) 6 (3)
Totals 40 107 62 203

Table 29.

Anesthetics-local and general

Agent 2010 (%) 2011 (%) 2012 (%) Total (%)
Local anesthetics Lidocaine 2 (50) 6 (60) 8 (50) 16 (53)
Benzocaine 2 (50) 2 (20) 3 (19) 7 (23)
Bupivacaine 0 (0) 1 (10) 2 (13) 3 (10)
Articaine 0 (0) 0 (0) 1 (6) 1 (3)
Menthol 0 (0) 0 (0) 1 (6) 1 (3)
Ropivacaine 0 (0) 0 (0) 1 (6) 1 (3)
Mepivacaine 0 (0) 1 (10) 0 (0) 1 (3)
TOTALS 4 10 16 30
General anesthetics Ketamine 1 (20) 2 (22) 6 (46) 9 (33)
Propofol 1 (20) 4 (44) 4 (31) 9 (33)
Sevoflurane 1 (20) 1 (11) 1 (8) 3 (11)
Isoflurane 0 (0) 1 (11) 1 (8) 2 (8)
Dexmedetomidine 0 (0) 0 (0) 1 (8) 1 (4)
Etomidate 0 (0) 1 (11) 0 (0) 1 (4)
Nitrous oxide 1 (20) 0 (0) 0 (0) 1 (4)
Unspecified general anesthetic 1 (20) 0 (0) 0 (0) 1 (4)
Totals 5 9 13 27
Neuromuscular blocking agents Succinylcholine 0 (100) 2 (100) 1 (100) 3 (100)
Totals 9 21 30 30

The non-ethanol alcohols including the “toxic” alcohols ethylene glycol and methanol are included in Table 30. Ethylene glycol was reported in 51 % followed by isopropyl alcohol (26 %), acetone (6 %) and methanol (5 %).

Table 30.

Non-ethanol alcohols, methanol, isopropyl alcohol, ethylene glycol, other

Agent 2010 (%) 2011 (%) 2012 (%) Total (%)
Ethylene glycol 41 (43) 68 (47) 62 (51) 171 (48)
Isopropanol 20 (21) 34 (24) 31 (26) 85 (24)
Methanol 17 (18) 19 (13) 6 (5) 42 (12)
Acetone 3 (3) 8 (6) 7 (6) 18 (5)
Propylene glycol 0 (0) 5 (3) 4 (3) 9 (3)
Diethylene glycol 3 (3) 0 (0) 2 (2) 5 (1)
Glycol ether 4 (4) 3 (2) 1 (1) 8 (2)
2-butoxyethanol 0 (0) 1 (1) 0 (0) 1 (0)
Methyl ethyl ketone 0 (0) 1 (1) 1 (1) 2 (0)
Butanol 2 (2) 1 (1) 1 (1) 4 (1)
Diethyl ether 0 (0) 1 (1) 1 (1) 2 (0)
Triethylene glycol monobutyl ether 1 (1) 0 (0) 0 (0) 1 (0)
Other alcohols, glycols, ethers 4 (4) 3 (2) 5 (4) 12 (3)
Totals 95 144 121 360

Table 31 includes cases involving hydrocarbons. The most common hydrocarbon agents reported were gasoline (11 %) and benzene (11 %). A total of 45 hydrocarbon exposures were reported in 2012.

Table 31.

Hydrocarbons

Agent 2010 (%) 2011 (%) 2012 (%) Total (%)
Aliphatic Methane 2 (4) 6 (9) 4 (9) 12 (8)
Hexane 2 (4) 2 (3) 0 (0) 4 (3)
Other aliphatic 0 (0) 4 (6) 0 (0) 4 (3)
Aromatic Benzene 3 (6) 3 (5) 5 (11) 11 (7)
Naphthalene 0 (0) 3 (5) 2 (5) 5 (3)
Xylene 3 (6) 3 (5) 1 (2) 7 (4)
Ethylenzene 0 (0) 2 (3) 1 (2) 3 (2)
Toluene 0 (0) 1 (2) 3 (7) 4 (3)
Other Gasoline 1 (2) 4 (6) 5 (11) 10 (6)
Kerosene 2 (4) 3 (5) 1 (2) 6 (2)
Mineral oil 0 (0) 1 (2) 1 (2) 2 (1)
Paraffin oil 0 (0) 1 (2) 2 (5) 3 (2)
Tetrachloroethylene 1 (2) 5 (8) 0 (0) 6 (2)
Methylene chloride 1 (2) 4 (6) 2 (5) 7 (4)
Trichloroethylene 4 (8) 2 (3) 1 (2) 7 (4)
Difluoroethane 3 (6) 1 (2) 3 (7) 7 (4)
Dichloroethane 0 (0) 1 (2) 0 (0) 1 (0)
Ethyl chloride 0 (0) 1 (2) 1 (2) 2 (1)
Chlorofluorocarbons 0 (0) 1 (2) 1 (2) 2 (1)
Other hydrocarbons 28 (56) 16 (25) 12 (27) 56 (36)
Totals 50 67 45 159

Table 32 shows the number of cases involving metals and metalloids. Lead (22 %) surpassed iron (18 %) as the most common metal type reported in 2012. Mercury (15 %), cobalt (10 %), and chromium (9 %) were common metal and metalloid agents reported in 2012.

Table 32.

Metals and metalloids

Agent 2010 (%) 2011 (%) 2012 (%) Total (%)
Lead 30 (20) 46 (14) 49 (22) 125 (18)
Iron 12 (8) 48 (15) 41 (18) 101 (15)
Chromium 4 (3) 41 (13) 20 (9) 45 (6)
Cobalt 1 (0) 40 (13) 23 (10) 64 (9)
Arsenic 14 (9) 32 (10) 14 (6) 60 (9)
Cadmium 31 (20) 25 (8) 9 (4) 65 (9)
Mercury 21 (14) 25 (8) 33 (15) 79 (11)
Selenium 31 (21) 24 (8) 9 (4) 64 (9)
Coppers 1 (0) 6 (2) 4 (2) 11 (2)
Aluminum 2 (1) 4 (1) 5 (2) 11 (2)
Cesium 0 (0) 4 (1) 1 (0) 5 (1)
Vanadium 0 (0) 0 (0) 3 (1) 3 (0)
Thallium 0 (0) 4 (1) 1 (0) 5 (1)
Magnesium 0 (0) 3 (1) 0 (0) 3 (0)
Gadolinium 1 (0) 2 (1) 1 (0) 4 (1)
Gold 1 (0) 2 (1) 0 (0) 3 (0)
Nickel 1 (0) 2 (1) 3 (1) 6 (1)
Barium chromate 0 (0) 1 (0) 1 (0) 2 (0)
Beryllium 0 (0) 1 (0) 1 (0) 2 (0)
Platinum 0 (0) 1 (0) 2 (1) 3 (1)
Rhodium 0 (0) 1 (0) 0 (0) 1 (0)
Uranium 0 (0) 0 (0) 2 (1) 2 (0)
Tungsten 0 (0) 0 (0) 1 (0) 1 (0)
Other metals 0 (0) 6 (2) 4 (2) 10 (2)
Totals 150 318 227 695

Table 33 shows the gas, vapors, dust, and irritant agents. Carbon monoxide was the most common reported agent in this class again in 2012 with 80 entries (67 %). Chlorine (6 %) and cyanide exposure (4 %) were the two next most common gas exposures in 2012.

Table 33.

Gas, vapors, irritants

Agent 2010 (%) 2011 (%) 2012 (%) Total (%)
Carbon monoxide 44 (63) 130 (73) 80 (67) 254 (71)
Chlorine 9 (13) 9 (5) 7 (6) 25 (7)
Smoke 0 (0) 9 (5) 4 (3) 13 (4)
Cyanide 3 (4) 2 (1) 5 (4) 10 (3)
Hydrogen sulfide 2 (3) 2 (1) 2 (2) 6 (2)
Arsine gas 0 (0) 1 (0) 4 (3) 5 (1)
Phosphine 0 (0) 0 (0) 4 (3) 4 (1)
Bromine 0 (0) 1 (0) 1 (1) 2 (0)
Natural gas 0 (0) 1 (0) 4 (3) 5 (1)
Oxides of nitrogen 0 (0) 3 (2) 1 (1) 4 (1)
Petroleum vapors 0 (0) 2 (1) 4 (3) 6 (2)
Polyurethane vapors 0 (0) 1 (0) 0 (0) 1 (0)
Dust 5 (7) 4 (2) 4 (3) 13 (4)
Soot 0 (0) 1 (0) 0 (0) 1 (0)
Other vapors, fumes or gases 7 (10) 12 (7) 9 (8) 28 (3)
Totals 70 178 129 377

Table 34 shows caustic agent entries. Acids made up 26 % of caustic exposures with hydrochloric (3 %) and hydrofluoric (6 %) acids reported in a similar number of case entries. Alkaline substances made up 34 % of caustic exposures and sodium hydroxide (36 %) was the most common alkaline agent reported.

Table 34.

Caustic Agents

Agent 2010 (%) 2011 (%) 2012 (%) Total (%)
Acids Hydrochloric acid 4 (8) 14 (15) 3 (6) 21 (11)
Citric acid 0 (0) 4 (4) 0 (0) 4 (2)
Acetic acid 4 (8) 2 (2) 1 (2) 7 (4)
Hydrofluoric acid 0 (0) 2 (2) 3 (6) 5 (2)
Sulfuric acid 1 (2) 1 (1) 0 (0) 2 (1)
Phosphoric acid 0 (0) 1 (1) 0 (0) 1 (0)
Nitric acid 0 (0) 0 (0) 2 (4) 2 (1)
Phenol 2 (4) 1 (1) 0 (0) 3 (2)
Other acid 2 (4) 2 (2) 3 (6) 7 (4)
Bases Sodium hydroxide 5 (10) 21 (23) 8 (17) 34 (18)
Sodium hypochlorite 13 (27) 20 (22) 1 (2) 34 (18)
Ammonia 4 (8) 7 (8) 5 (11) 16 (8)
Potassium hydroxide 3 (6) 3 (3) 4 (9) 10 (5)
Ammonia chloride 3 (6) 0 (0) 1 (2) 4 (2)
Ammonium nitrates 1 (2) 0 (0) 0 (0) 1 (0)
Other base/alkaline 1 (2) 1 (1) 8 (17) 10 (5)
Hydrogen peroxide Hydrogen peroxide 3 (6) 11 (12) 3 (6) 17 (9)
Other caustics Other caustic 3 (6) 3 (3) 8 (17) 14 (7)
Totals 45 98 47 189

Table 35 shows herbals, supplement, and vitamin agents. Table 36 describes plant and fungi exposures.

Table 35.

Herbals, supplements, vitamins

Agent 2010 N (%) 2011 N (%) 2012 N (%) Total N (%)
Aethusa cynapium 0 (0) 0 (0) 1 (2) 1 (0)
Artemisia sp. (mugwort) 1 (3) 0 (0) 0 (0) 1 (0)
Caper bush 0 (0) 1 (1) 0 (0) 1 (0)
Chicory 0 (0) 1 (1) 0 (0) 1 (0)
Citronella 1 (3) 1 (1) 0 (0) 2 (1)
Echinacea 1 (3) 2 (2) 0 (0) 3 (2)
Sambucus sp. (elderberry extract) 0 (0) 1 (1) 0 (0) 1 (0)
Ephedra 0 (0) 1 (1) 1 (2) 2 (1)
Eucalyptus oil 0 (0) 1 (1) 0 (0) 1 (0)
Fox nut 0 (0) 1 (1) 0 (0) 1 (0)
Fragrant lemongrass oil 0 (0) 1 (1) 0 (0) 1 (0)
Panax sp. (ginseng) 0 (0) 1 (1) 2 (4) 3 (2)
Grapefruit extract 0 (0) 1 (1) 0 (0) 1 (0)
Jojoba oil 0 (0) 1 (1) 0 (0) 1 (0)
Melatonin 1 (3) 10 (10) 10 (20) 21 (11)
Probiotics 0 (0) 1 (1) 0 (0) 1 (0)
Prunus cerasus 0 (0) 0 (0) 1 (2) 1 (0)
Ruta gaveolens (Ruta 6) 6 (15) 1 (1) 0 (0) 7 (4)
Seman persicae (peach kernel) 0 (0) 1 (1) 1 (2) 2 (1)
Serenoa repens (saw palmetto) 0 (0) 0 (0) 1 (2) 1 (0)
Soy lecithin 0 (0) 1 (1) 1 (2) 2 (1)
St. John’s wort (Hypericum perforatum) 0 (0) 1 (1) 0 (0) 1 (0)
Tamarisk 0 (0) 1 (1) 0 (0) 1 (0)
Tea tree oil 0 (0) 1 (1) 0 (0) 1 (0)
Tuckahoe (Wolfiporia extensa) 0 (0) 1 (1) 0 (0) 1 (0)
Urtica sp. (nettle leaf) 1 (3) 0 (0) 0 (0) 1 (0)
Valeriana officinalis 0 (0) 1 (1) 1 (2) 2 (1)
Whey protein concentrate 0 (0) 1 (1) 0 (0) 1 (0)
Yarrow 0 (0) 1 (1) 0 (0) 1 (0)
Yerba mate 0 (0) 1 (1) 0 (0) 1 (0)
Yohimbine 0 (0) 1 (1) 1 (2) 2 (1)
Other herbal or supplement 14 (35) 16 (15) 8 (16) 38 (20)
Totals 25 (63) 52 (50) 28 (56) 95 (51)
Vitamins Multivitamins (MVI) 1 (3) 11 (10) 5 (10) 17 (9)
Vitamin D 1 (3) 9 (9) 0 (0) 10 (5)
Calcium 1 (3) 8 (5) 0 (0) 9 (5)
Potassium 4 (10) 5 (5) 1 (2) 10 (5)
Zinc 5 (13) 5 (5) 2 (4) 12 (6)
Vitamin C (ascorbic acid) 1 (3) 3 (3) 1 (2) 4 (2)
Vitamin B9 (folic acid) 0 (0) 3 (3) 1 (2) 4 (2)
Vitamin B3 (niacin) 1 (3) 2 (2) 7 (14) 10 (5)
Prenatal vitamins 0 (0) 2 (2) 2 (4) 4 (2)
Biotin 0 (0) 1 (1) 0 (0) 1 (0)
Vitamin B12 (cyanocobalamin) 0 (0) 1 (1) 1 (2) 2 (1)
Vitamin B1 (thiamine) 2 (5) 1 (1) 1 (2) 2 (1)
Vitamin K (phytonadione) 0 (0) 1 (1) 0 (0) 1 (0)
Vitamin A 1 (3) 0 (0) 1 (2) 2 (1)
Vitamin E 0 (0) 0 (0) 1 (2) 1 (0)
Totals vitamins 15 (38) 52 (50) 22 (44) 92 (49)
Totals 40 104 50 194

Table 36.

Plants and fungi (mushrooms)

Agent 2010 N (%) 2011 N (%) 2012 N (%) Total N (%)
Plants Atropa belladonna (deadly nightshade) 1 (4) 0 (0) 1 (2) 2 (2)
Areca catechu (betel nut) 0 (0) 1 (2) 0 (2) 1 (1)
Datura inoxia (moonflower) 0 (0) 1 (2) 6 (12) 7 (5)
Nerium oleander (oleander) 1 (4) 0 (0) 0 (2) 1 (1)
Parthenocissus quinquefolia (Virginia creeper) 1 (4) 0 (0) 0 (2) 1 (1)
Taxus sp. (yew) 2 (7) 0 (0) 0 (2) 2 (2)
Thevetia peruviana (yellow oleander) 0 (0) 1 (2) 1 (2) 2 (2)
Unspecified or other plant 2 (7) 1 (2) 2 (4) 5 (4)
Total plants 7 (25) 4 (7) 10 (19) 21 (15)
Mushrooms Amanita bisporigera (destroying angel) 0 (0) 0 (0) 1 (2) 1 (1)
Amanita sp. 2 (7) 3 (5) 4 (8) 10 (7)
Galerina 0 (0) 1 (2) 0 (0) 1 (1)
Morcella sp. (morel) 0 (0) 1 (2) 0 (0) 1 (1)
Psylocybin containing 1 (4) 1 (2) 2 (4) 4 (3)
Unspecified cyclopeptide-containing 0 (0) 3 (5) 1 (2) 4 (3)
Unspecified non-toxic 1 (4) 0 (0) 1 (2) 2 (2)
Unspecified mushrooms 1 (4) 10 (17) 6 (12) 17 (12)
Total mushrooms 5 (18) 19 (32) 15 (29) 39 (26)
Molds Unspecified molds 13 (46) 36 (61) 27 (52) 76 (55)
Stachybotrys sp. 2 (7) 0 (0) 0 (2) 2 (1)
Aspergillus 1 (4) 0 (0) 0 (2) 1 (1)
Total molds 16 (57) 36 (61) 27 (52) 79 (57)
Totals 28 59 52 139

Envenomation cases make up Table 37. Snakebites make up the majority of envenomation entries again in 2012. Crotalus species or “rattlesnakes” make up the majority of snake envenomation entries. Rattlesnakes were reported in 43 % of all envenomation cases. Agkistrodon contortrix or “copperhead” snakes were the second most frequently reported species with 20 % of cases from copperhead envenomation in 2012. Loxosceles reclusa or “brown recluse” spiders accounted for 20 cases (10 %) of envenomation and Lactrodectus mactans or “black widows” accounted for 15 (8 %). Scorpions accounted for 9 % of envenomations with most scorpion envenomations unspecified in terms of type of scorpion.

Table 37.

Envenomations

Envenomation type Species 2010 (%) 2011 (%) 2012 (%) Total (%)
Snake Rattlesnake (unspecified) 39 (36) 53 (29) 57 (29) 149 (31)
Crotalus sp. 5 (5) 3 (2) 25 (13) 33 (7)
Crotalus atrox (western diamond back) 0 (0) 2 (1) 2 (1) 4 (1)
Crotalus scutulatus (Mojave rattlesnake) 0 (0) 0 (0) 1 (0) 1 (0)
Crotalus horridus (timber rattlesnake) 1 (1) 1 (0) 0 (0) 2 (0)
Crotalus mitchelii (speckled rattlesnake) 0 (0) 1 (0) 0 (0) 1 (0)
Sistrurus miliarius (pygmy rattlesnake) 0 (0) 1 (0) 0 (0) 1 (0)
Crotalus viridis viridis (prairie rattlesnake) 1 (1) 0 (0) 0 (0) 2 (0)
Agkistrodon contortrix (copperhead) 20 (19) 41 (22) 39 (20) 100 (20)
Agkistrodon sp. 0 (0) 0 (0) 3 (2) 3 (0)
Unspecified snake 2 (2) 11 (6) 2 (1) 15 (31)
Agkistrodon piscivorus (water moccasin) 0 (0) 3 (2) 2 (1) 5 (1)
Vipera palestinae (Palestine viper) 0 (0) 2 (1) 0 (0) 2 (0)
Bitis gabonica (Gabon viper) 0 (0) 1 (0) 0 (0) 1 (0)
Coluber jugularis (black whip snake) 0 (0) 1 (0) 0 (0) 1 (0)
Bothriechis schlegelii (eyelash viper) 1 (1) 0 (0) 0 (0) 1 (0)
Micrurus sp. (eastern coral snake) 1 (1) 0 (0) 0 (0) 1 (0)
Nonvenous snake—unspecified 0 (0) 2 (1) 2 (1) 4 (1)
Totals snakes 70 (65) 122 (66) 133 (68) 325 (67)
Spiders Loxosceles reclusa (brown recluse) 9 (8) 19 (10) 20 (10) 48 (10)
Latrodectus mactans (black widow) 0 (0) 7 (4) 15 (8) 22 (5)
Wolf spider 0 (0) 1 (0) 1 (0) 2 (0)
Orb weaver spider 0 (0) 0 (0) 1 (0) 1 (0)
Unspecified spider 1 (1) 3 (2) 3 (2) 7 (2)
Total spiders 10 (9) 30 (16) 40 (20) 80 (16)
Scorpions Unspecified scorpions 26 (24) 21 (11) 12 (6) 59 (12)
Centuroides sculpturatus (bark scorpion) 0 (0) 5 (2) 6 (3) 11(2) (1)
Total scorpions 26 (24) 26 (14) 18 (9) 70 (14)
Other Pterois sp. (lion fish) 0 (0) 1 (0) 1 (0) 2 (0)
Heloderma suspectum (gila monster) 0 (0) 2 (1) 0 (0) 2 (0)
Portuguese man-of–war 0 (0) 1 (0) 0 (0) 1 (0)
Other envenomations 2 (2) 2 (1) 4 (2) 8 (2)
Totals other 2 (2) 6 (4) 5 (3) 13 (3)
Total envenomations 108 184 196 488

Table 38 describes agents involved in weapons of mass destruction (WMD), nuclear and biologic chemicals (NBC) and riot agent exposures. Household products not falling into any of the agent classes listed thus far were not included separately in a table as most agents that fell into this category were included as specific products or with generic names. The majority of these agents were soaps, detergents, and cleaning agents.

Table 38.

WMD, NBC and riot control agent exposures

Agent 2010 N (%) 2011 N (%) 2012 N (%) Total N (%)
WMD or warfare agent Ricin 0 (0) 1 (14) 3 (75) 4 (33)
Trichothecene mycotoxin 0 (0) 0 (0) 1 (25) 1 (8)
Osmium tetraoxide 0 (0) 1 (14) 0 (0) 1 (8)
Riot control agents Unspecified 0 (0) 1 (14) 0 (0) 1 (8)
Radiation Radiation various 0 (0) 3 (43) 0 (0) 3 (25)
Radon 1 (100) 0 (0) 0 (0) 1 (8)
Explosive Cyclotrimethylenetrinitramine (RDX) 0 (0) 1 (14) 0 (0) 1 (8)
Totals 1 7 4 12

ADR-related consultations shown in Table 39. Lithium (7 %) remained the most common agent reported in ADRs followed by digoxin (4 %). There were 102 different specific medications described in Table 39. Only drugs listed at least twice were included in the ADR table.

Table 39.

Adverse drug reactions in the registry

Agent 2011 N (%) 2012 N (%) Total N (%)
Lithium 24 (4) 30 (7) 54 (5)
Digoxin 22 (4) 16 (4) 38 (4)
Acetaminophen 21 (4) 6 (1) 27 (3)
Trazodone 15 (3) 7 (2) 22 (2)
Citalopram 14 (2) 11 (3) 25 (3)
Quetiapine 14 (2) 7 (2) 21 (2)
Valproic acid 14 (2) 7 (2) 21 (2)
Oxycodone 13 (2) 14 (3) 27 (3)
Risperidone 12 (2) 10 (3) 22 (2)
Venlafaxine 12 (2) 7 (2) 19 (2)
Bupropion 11 (2) 4 (1) 15 (2)
Olanzapine 11 (2) 2 (0) 13 (1)
Diphenhydramine 10 (2) 4 (1) 14 (1)
Lamotrigine 10 (2) 7 (2) 17 (2)
Lisinopril 10 (2) 2 (0) 12 (1)
Clonazepam 9 (2) 7 (2) 16 (2)
Fluoxetine 9 (2) 4 (1) 13 (1)
Haloperidol 9 (2) 6 (2) 15 (2)
Aripiprazole 8 (1) 3 (1) 11 (1)
Clozapine 8 (1) 2 (0) 10 (1)
Fentanyl 8 (1) 7 (2) 15 (2)
Lorazepam 8 (1) 5 (1) 13 (1)
Metoprolol 8 (1) 2 (0) 10 (1)
Mirtazepine 8 (1) 2 (0) 10 (1)
Phenytoin 8 (1) 9 (3) 17 (2)
Baclofen 7 (1) 7 (2) 14 (1)
Busparone 7 (1) 5 (1) 12 (1)
Ethanol 7 (1) 4 (1) 11 (1)
Hydrocodone 7 (1) 2 (0) 9 (1)
Methadone 7 (1) 7 (2) 14 (1)
Methylphenidate NA (0) 7 (2) 7 (1)
Hydromorphone 7 (1) 2 (0) 9 (1)
Benztropine 6 (1) 4 (1) 10 (1)
Caffeine 6 (1) 2 (0) 8 (1)
Carbamazepine 6 (1) 4 (1) 10 (1)
Dextromethorphan 6 (1) 6 (1) 12 (1)
Glyburide 6 (1) 5 (1) 11 (1)
Metformin 6 (1) 5 (1) 11 (1)
Setraline 6 (1) 9 (2) 15 (2)
Tramadol 6 (1) 5 (1) 11 (1)
Alprazolam 5 (1) 4 (1) 9 (1)
Carisoprodol 5 (1) 2 (0) 7 (1)
Clonidine 5 (1) 2 (0) 7 (1)
Diltiazepam 5 (1) 4 (1) 9 (1)
Gabapentin 5 (1) 6 (1) 11 (1)
Hydrochlorothiazide 5 (1) 5 (1) 10 (1)
Morphine 5 (1) 3 (1) 8 (1)
Omeprazole 5 (1) 2 (0) 7 (1)
Prednisone 5 (1) 5 (1) 10 (1)
Propranolol 5 (1) 2 (0) 7 (1)
Sulfamethoxazole 5 (1) 2 (0) 7 (1)
Ziprasidone 5 (1) 2 (0) 7 (1)
Zolpidem 5 (1) 2 (0) 7 (1)
Amitriptyline 4 (1) 4 (1) 8 (1)
Amphetamine 4 (1) 2 (0) 6 (1)
Aspirin 4 (1) 2 (0) 6 (1)
Cyclobenzaprine 4 (1) 2 (0) 6 (1)
Duloxetine 4 (1) 4 (1) 8 (1)
Hydroxyzine 4 (1) 2 (0) 6 (1)
Ibuprofen 4 (1) 2 (0) 6 (1)
Promethazine 4 (1) 2 (0) 6 (1)
Trimethoprim 4 (1) 2 (0) 6 (1)
Verapamil 4 (1) 2 (0) 6 (1)
Amlodipine 3 (1) 2 (0) 5 (1)
Atenolol 3 (1) 2 (0) 5 (1)
Buprenorphine 3 (1) 2 (0) 5 (1)
Carvedilol 3 (1) 2 (0) 5 (1)
Codeine 3 (1) 2 (0) 5 (1)
Dextroamphetamine 3 (1) 4 (1) 7 (1)
Diazepam 3 (1) 2 (0) 5 (1)
Doxepine NA (0) 2 (0) 2 (0)
Escitalopram 3 (1) 2 (0) 5 (1)
Loxapine 3 (1) 2 (0) 5 (1)
Metronidazole 3 (1) 2 (0) 5 (1)
Prochlorperazine 3 (1) 2 (0) 5 (1)
Propofol 3 (1) 3 (1) 6 (1)
Ranitidine 3 (1) 2 (0) 5 (1)
Topiramate 3 (1) 2 (0) 5 (1)
Amoxicillin 2 (0) 2 (0) 4 (0)
Atomoxetine 2 (0) 2 (0) 4 (0)
Azithromycin 2 (0) 2 (0) 4 (0)
Benzocaine NA (0) 2 (0) 2 (0)
Chromium 2 (0) 2 (0) 4 (0)
Cobalt 2 (0) 2 (0) 4 (0)
Cocaine 2 (0) 2 (0) 4 (0)
Dabigatran NA (0) 2 (0) 2 (0)
Dapsone 2 (0) 2 (0) 4 (0)
Dilantin 2 (0) NA (0) 2 (0)
Disulfiram 2 (0) NA (0) 2 (0)
Doxylamine 2 (0) 2 (0) 4 (0)
Famotidine 2 (0) NA (0) 2 (0)
Fluvoxamine 2 (0) NA (0) 2 (0)
Fondaparinux 2 (0) NA (0) 2 (0)
Furosemide 2 (0) NA (0) 2 (0)
Glimepride NA (0) 2 (0) 2 (0)
Glipizide NA (0) 2 (0) 2 (0)
Guanfacine 2 (0) NA (0) 2 (0)
Hyosyamine 2 (0) 5 (1) 7 (1)
Iron 0 2 (0) 2 (0)
Isoniazid 2 (0) 3 (1) 5 (1)
Linezolid 2 (0) NA (0) 2 (0)
Methotrexate NA (0) 2 (0) 2 (0)
Naloxone 2 (0) NA (0) 2 (0)
Oxcarbazepine 2 (0) 2 (0) 4 (0)
Perphenazine 2 (0) NA (0) 2 (0)
Phentermine NA (0) 3 (1) 3 (0)
Piperacillin 2 (0) 2 (0) 4 (0)
Polyethylene glycol 2 (0) 2 (0) 4 (0)
Pregabalin 2 (0) 3 (1) 5 (1)
Pseudoephedrine 2 (0) NA (0) 2 (0)
Ritonavir 2 (0) NA (0) 2 (0)
Senna 2 (0) NA (0) 2 (0)
Tolterodine 2 (0) 2 (0) 4 (0)
Triamterine 2 (0) 0 (0) 2 (0)
Vancomycin NA (0) 2 (0) 2 (0)
Warfarin 2 (0) NA (0) 2 (0)
593 405 998

Table 40 includes information about antidotes used during 2012. N-acetylcysteine (NAC) was the most frequently administered antidote in 2012 making up 30 % of all antidote entries. Naloxone was the second most common antidote used (19 %) followed by sodium bicarbonate (12 %), physostigmine (11 %), and flumazenil (7 %).

Table 40.

Antidotal agents reported to have been used in cases in the registry

Antidote 2010 N (%) 2011 N (%) 2012 N (%) Total N (%)
2-Pam 0 (0) 1 (0) 3 (0) 4 (0)
Atropine 1 (1) 30 (1) 29 (1) 60 (1)
Botulinum antitoxin 0 (0) 1 (0) 4 (0) 5 (0)
Bromocriptine 0 (0) 1 (0) 2 (0) 3 (0)
Calcium 2 (2) 65 (0) 52 (2) 119 (2)
Carnitine 0 (0) 14 (0) 35 (2) 49 (1)
Cyproheptadine 0 (0) 24 (1) 17 (1) 41 (1)
Dantrolene 0 (0) 2 (0) 5 (0) 7 (0)
Ethanol 0 (0) 5 (0) 0 (0) 5 (0)
Digoxin Fab 1 (1) 20 (1) 24 (1) 45 (1)
Flumazenil 9 (12) 155 (6) 182 (7) 346 (7)
Folate 1 (1) 54 (2) 46 (2) 111 (2)
Fomepizole 4 (5) 103 (4) 68 (3) 175 (3)
Glucagon 2 (2) 66 (2) 52 (2) 130 (3)
Hydroxocobalamin 0 (0) 8 (0) 10 (0) 18 (0)
Hyperinsulinemia euglycemia therapy (HIT) 1 (1) 28 (1) 16 (0) 45 (1)
Lipid rescue 1 (1) 20 (1) 23 (1) 44 (1)
Methylene blue 0 (0) 5 (0) 12 (0) 17 (0)
N-acetylcysteine (NAC) 27 (35) 798 (30) 707 (29) 1,532 (30)
Naloxone 17 (22) 498 (19) 458 (19) 973 (19)
Nitrites 0 (0) 2 (0) 2 (0) 4 (0)
Octreotide 1 (1) 19 (1) 24 (1) 44 (1)
Physostigmine 11 (14) 228 (9) 262 (11) 501 (10)
Pyridoxine 1 (1) 28 (1) 7 (0) 36 (1)
Sodium bicarbonate 14 (18) 315 (12) 288 (12) 617 (12)
Thiamine 3 (4) 109 (4) 81 (3) 193 (4)
Thiosulfate 0 (0) 3 (0) 4 (0) 7 (0)
Vitamin K 3 (4) 48 (2) 15 (0) 66 (1)
Totals 78 2,651 2,428 5,157

Table 41 describes antivenom use. CroFab was used 109 times (83 % of antivenom entries) followed by scorpion antivenom (10 %) and spider antivenom (5 %). Other snake antivenoms were used twice (2 %) in 2012.

Table 41.

Antivenom use

Antivenom 2012 N (%)
CroFab 109 (83)
Other snake antivenom 2 (2)
Scorpion 13 (10)
Spider 7 (5)
Total 131

Table 42 includes chelators used by medical toxicologists in 2012. Succimer (DMSA) was reported 18 times (51 %) followed by deferoxamine 6 times (17 %) and British Anti Lewisite (BAL) 5 times (14 %). The other chelators used were ethylenediaminetetraacetic acid (EDTA) (11 %), unithiol (DMPS) (3 %) and penicillamine (3 %).

Table 42.

Chelators used

Chelators 2012 N (%)
DMSA 18 (51)
Deferoxamine 6 (17)
BAL 5 (14)
EDTA 4 (11)
DMPS 1 (3)
Penicillamine 1 (3)
Total 35

Table 43 shows decontamination treatments utilized in 2012. Activated charcoal topped the list with 280 entries (81 % of decontamination events), followed by whole bowel irrigation with 41 occurrences (14 %) and gastric lavage with 22 occurrences (6 %).

Table 43.

Decontamination

Decontamination 2012 N (%)
Activated charcoal 280 (81)
Gastric lavage 22 (6)
Sorbitol 1 (0)
Whole bowel irrigation 41 (12)
Total 344

Drug and toxin elimination treatments are described in Table 44. Hemodialysis was reported 126 times (46 %) followed by urinary alkalinization with 61 occurrences (22 %). Multidose activated charcoal (MDAC) was used in 53 cases (19 %) and continuous renal replacement therapy (CVVHD) was reported 35 times (13 %).

Table 44.

Toxin elimination treatments reported in 2012

Elimination 2012 N (%)
Urinary alkalinization 61 (22)
Continuous renal replacement therapy (CVVHD, etc.) 35 (12)
MDAC 53 (19)
Hemodialysis 126 (46)
Total 275

Non-pharmacologic support is described in Table 45. The most common non-pharmacologic support used in 2012 included intravenous fluid resuscitation, reported 1,294 times (67 %), followed by intubation and ventilator management reported 555 times (29 %). Cardiopulmonary resuscitation (CPR) was done in 36 cases.

Table 45.

Non-pharmacologic support

Non-pharmacologic support 2012 N (%)
IV fluid resuscitation 1,294 (66)
Intubation/ventilatory management 555 (28)
CPR 36 (2)
Hyperbaric oxygen 16 (1)
Transfusion 12 (1)
Pacemaker 8 (1)
Cardioversion 5 (0)
Other 17 (1)
Total 1,943

Benzodiazepines were the most common agents used for pharmacologic support by medical toxicologists with 1,242 cases using these agents in patient care (57 %). Antipsychotics were used in 9 % of cases involving pharmacologic support, vasopressors in 9 % and non-benzodiazepine anticonvulsants in 5 %. Other drugs used in pharmacologic support by medical toxicologists are included in Table 46.

Table 46.

Pharmacologic support utilized in cases reported to the Registry in 2012

Pharmacologic support 2012 N (%)
Benzodiazepines 1,242 (57)
Antipsychotics 205 (9)
Vasopressors 198 (9)
Anticonvulsants 113 (5)
Glucose >5 % 83 (4)
Opioids 83 (4)
Steroids 39 (2)
Albuterol and other bronchodilators 35 (2)
Neuromuscular blockers 26 (1)
Beta blockers 17 (1)
Antihypertensives 16 (1)
Antiarrhythmics 13 (1)
Clonidine 13 (1)
Phenobarbital 8 (0)
Vasodilators 8 (0)
Antiemetics 6 (0)
Propofol 5 (0)
Totala 2,172

aOnly support used more than five specific times were included in the above table. The total number of times “Pharmacologic Support” was used, however, was left intact. Often single entries were agents that should have been included only as antidote (i.e., naloxone) and not indicated as used for pharmacologic support

Discussion

2012 marks the third year of data collection for the ACMT ToxIC Registry; 17,681 cases were entered by December 31st, 2012. Additional enhancements and development of the Registry infrastructure were completed in 2012 including the addition of a data dictionary to facilitate agent entry and surveillance. Several noteworthy publications were generated from Registry data in 2012 including a report describing important new information on infant and toddler poisonings [4]. Additional work involving toxico-surveillance began in 2012 including preliminary development of a prospective Registry for cases involving prescription opioid abuse.

Sedative-hypnotics remained the most common agents reported in 2012. Clonazepam and alprazolam remained at the top of the list. Sedative-hypnotics and muscle relaxants are frequently reported in cases involving prescription abuse and are only secondary to opioid analgesics in this respect. Many of the opioid-related fatalities that occur in the USA also involve sedative-hypnotics and muscle relaxants as co-ingestants. This combination is particularly lethal in that the degree of impairment to respiration and ventilation may be more severe when these agents are taken together. With nearly 1,500 sedative-hypnotic and muscle relaxant entries occurring annually the ToxIC Registry this represents an excellent mode of toxico-surveillance as well as a source for prospective study regarding the role of sedatives in poisonings and prescription drug abuse-related hospitalizations in particular.

2012 data also confirms the ongoing role of over-the-counter agents in medication abuse. Dextromethorphan was one of the most commonly abused psychoactive agents in 2012 with more references than other commonly abused drugs such as amphetamine or methamphetamine. Dextromethorphan was also reported more frequently than synthetic cannabinoids and designer amphetamines including MDMA and psychoactive bath salts in 2012. In 2012, drug abuse was split into multiple different categories in order to better track the role specific medications in these cases. This occurred half-way through the year in 2012. These modifications to the Registry data entry form will allow for better identification and toxico-surveillance regarding drug abuse-related hospitalizations.

Oxycodone was again the most common opioid encountered in patients seen by medical toxicologists in 2012. Opioids were encountered nearly 1,100 times in 2012. The data regarding prescription opioid exposures appears essentially stable with no major increases or decreases involving specific opioids over the past 2 years. Heroin, which had shown an increase from 2010 to 2011, remained a common cause of opioid-related consultation in 2012. With the further attention to prescription opioid abuse by the legal and medical establishments in 2012, many experts believe heroin use will continue to increase in the coming years. The ToxIC Registry is involved in active surveillance regarding prescription and illicit opioid-related abuse and hospitalizations. In 2013, a major sub-Registry study of cases involving misuse of prescription opioids was initiated.

While 2011 marked dramatic increases in designer drug-related hospitalizations compared to 2010, broad federal and state legislation introduced in the summer of 2012 appeared to be effective in reducing Emergency Department visits and hospitalization related to these substances. In fact, 2012 data regarding synthetic and designer drugs remained relatively flat compared to 2011 and some of the more common chemicals that had been sold as psychoactive bath salts such as MDPV and mephedrone, saw significant decreases in 2012 Registry data. Overall-stimulant related entries decreased slightly from 761 in 2011 to 692 in 2012 despite more centers entering cases. Cocaine remained the most common stimulant agent reported in 2012 as it was in 2010 and 2011. Psychostimulant use remained relatively constant although certain agents fluctuated in prevalence; amphetamine was reported less frequently while methylphenidate reports doubled in 2012. This data indicates that psychostimulants continue to cause significant morbidity and mortality in the US.

Several new designer drugs were encountered in 2012 with the “N-Bomb” agents (N-benzyl-ortho-methoxy 2C compounds), ultra-potent hallucinogenic amphetamines active in the 200–500 microgram range, newly identified in Registry entries in 2012. 2012 LSD reports increased dramatically and while not analytically confirmed it is thought that several of the LSD related cases were actually NBOME compounds misrepresented as “synthetic LSD”.

Whether synthetic cannabinoid and designer amphetamine drug use will show additional evidence of decreasing in 2013 remains to be seen; however, and regardless of this, novel substances continue to be reported regularly and remain a significant cause of morbidity and public health concern with several designer amphetamines in addition to the NBOME compounds being reported for the first time in the Registry in 2012. A real time toxico-surveillance system that can identify hospitalized patients and evolving and concerning trends related to synthetic and designer drug is increasingly important. This area represents an ongoing area of development and toxico-surveillance for the ToxIC Registry.

Limitations

The data reported herein is subject to several important limitations. ToxIC Registry numbers and trends should not be taken as representative of the use of these agents in the general population as the data reflects only those cases cared for at the bedside by medical toxicologists. This makes the sample representative of cases in which significant morbidity was experienced as cases in which patients were not hospitalized or had minimal signs or symptoms of toxicity are most likely underrepresented in the Registry. As a result, the Registry is more of a marker of significant toxicity or morbidity associated with drug and chemical exposures and envenomations than it is of general population exposures.

Another limitation is that in most cases the history of exposure is self-reported or comes from third-party sources. Inaccuracies in this aspect of data collection are a limitation in any data set of this type.

Quality assurance has remained an area of intense interest in the Toxicology Investigators Consortium. The ToxIC Steering Committee has developed a strategy to implement a quality assurance program which will introduce an additional degree of monitoring and lead to fewer inaccuracies and more complete case entries. Despite this, there may be some data that is incompletely or inaccurately reported. To this extent, it is most likely outcome data that are incomplete however, as evidenced by the increase in death cases reported in the Registry in 2012. Sites have been reminded to enter complete cases and to modify entries with significant developments after initially entered into the Registry. The possibility of incomplete data reporting should be less likely in subsequent years as the Registry further develops. Starting in 2012, death as an outcome was mandated to be reported to the Registry.

Acknowledgments

Funding for this project comes from the American College of Medical Toxicology.

Conflicts of Interest

None

References

  • 1.Wax PM, Kleinschmidt KC, Brent J. The Toxicology Investigators Consortium (ToxIC) Registry. J Med Toxicol. 2011;7(4):259–265. doi: 10.1007/s13181-011-0177-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Brent J, et al. The Toxicology Investigators Consortium Case Registry—the 2010 experience. J Med Toxicol. 2011;7(4):266–276. doi: 10.1007/s13181-011-0185-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Wiegand TJ, et al. The Toxicology Investigators Consortium Case Registry—the 2011 experience. J Med Toxicol. 2012;8(4):360–377. doi: 10.1007/s13181-012-0264-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Finkelstein Y, Hutson JR, Wax PM, Brent J, Toxicology Investigators Consortium (ToxIC) Case Registry (2012) Toxico-surveillance of infant and toddler poisonings in the United States. J med Toxicol 8(3):263–266 [DOI] [PMC free article] [PubMed]

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