Professional Documents
Culture Documents
Toxicology Update A Rational Approach To Managing The Poisoned Patient
Toxicology Update A Rational Approach To Managing The Poisoned Patient
A N E V I D E N C E - B A S E D A P P ROAC H T O E M E RG E N C Y M E D I C I N E
August 2001
Toxicology Update: A Rational Volume 3, Number 8
Editor-in-Chief Medicine, The University of Center, Atlantic Health System; School of Medicine; Attending University of Florida; Orlando
New Mexico Health Sciences Vice-Chairman, Department of Physician, UCLA Emergency Regional Medical Center; Medical
Stephen A. Colucciello, MD, FACEP, Center School of Medicine, Emergency Medicine, Morristown Medicine Center; Co-Director, Director of Orange County
Assistant Chair, Director of Albuquerque, NM. Memorial Hospital. The Doctoring Program, Emergency Medical Service,
Clinical Services, Department of W. Richard Bukata, MD, Assistant Michael A. Gibbs, MD, FACEP, UCLA School of Medicine, Orlando, FL.
Emergency Medicine, Carolinas Clinical Professor, Emergency Residency Program Director; Los Angeles, CA. Alfred Sacchetti, MD, FACEP,
Medical Center, Charlotte, NC; Medicine, Los Angeles County/ Medical Director, MedCenter Air, John A. Marx, MD, Chair and Chief, Research Director, Our Lady of
Associate Clinical Professor, USC Medical Center, Los Angeles, Department of Emergency Department of Emergency Lourdes Medical Center, Camden,
Department of Emergency CA; Medical Director, Emergency Medicine, Carolinas Medical Medicine, Carolinas Medical NJ; Assistant Clinical Professor
Medicine, University of North Department, San Gabriel Valley Center; Associate Professor of Center, Charlotte, NC; Clinical of Emergency Medicine,
Carolina at Chapel Hill, Chapel Medical Center, San Gabriel, CA. Emergency Medicine, University Professor, Department of Thomas Jefferson University,
Hill, NC. Francis M. Fesmire, MD, FACEP, of North Carolina at Chapel Hill, Emergency Medicine, University Philadelphia, PA.
Director, Chest Pain—Stroke Chapel Hill, NC. of North Carolina at Chapel Hill,
Associate Editor Corey M. Slovis, MD, FACP, FACEP,
Center, Erlanger Medical Center; Gregory L. Henry, MD, FACEP, Chapel Hill, NC.
Department of Emergency
Assistant Professor of Medicine, CEO, Medical Practice Risk Michael S. Radeos, MD, MPH, FACEP, Medicine, Vanderbilt University
Andy Jagoda, MD, FACEP, Professor UT College of Medicine, Assessment, Inc., Ann Arbor, Attending Physician in
of Emergency Medicine; Director, Hospital, Nashville, TN.
Chattanooga, TN. MI; Clinical Professor, Department Emergency Medicine, Lincoln
International Studies Program, Valerio Gai, MD, Professor and Chair, of Emergency Medicine, University Hospital, Bronx, NY; Research Mark Smith, MD, Chairman,
Mount Sinai School of Medicine, Department of Emergency of Michigan Medical School, Ann Fellow in Emergency Medicine, Department of Emergency
New York, NY. Medicine, University of Turin, Italy. Arbor, MI; President, American Massachusetts General Hospital, Medicine, Washington Hospital
Physicians Assurance Society, Ltd., Boston, MA; Research Fellow in Center, Washington, DC.
Michael J. Gerardi, MD, FACEP,
Editorial Board Clinical Assistant Professor, Bridgetown, Barbados, West Indies; Respiratory Epidemiology, Thomas E. Terndrup, MD, Professor
Medicine, University of Medicine Past President, ACEP. Channing Lab, Boston, MA. and Chair, Department of
Judith C. Brillman, MD, Residency and Dentistry of New Jersey; Jerome R. Hoffman, MA, MD, FACEP, Steven G. Rothrock, MD, FACEP, Emergency Medicine, University
Director, Associate Professor, Director, Pediatric Emergency Professor of Medicine/ FAAP, Associate Professor of Alabama at Birmingham,
Department of Emergency Medicine, Children’s Medical Emergency Medicine, UCLA of Emergency Medicine, Birmingham, AL.
volunteers taking sub-toxic amounts who receive decon- significance of urine or plasma drug levels. Toxicokinetics
tamination at a set post-ingestion time, or involve mildly to may also be used to predict the onset of symptoms and
moderately poisoned patients, excluding those with duration of toxicity.17
significant overdoses. Very few children have been included
in these trials. Differential Diagnosis
Well-controlled, randomized, human trials with
adequate sample sizes are infrequent. The conflicting Toxins may cause fever, headache, and abdominal pain;
literature regarding the utility of hyperbaric oxygen (HBO) indeed, any symptomatic patient can be a potential drug
therapy in carbon monoxide (CO) poisoning is one example overdose. Altered mental status, GI complaints, cardio-
where the absolute conviction of various experts is out- vascular compromise, and seizures can all be toxin-
weighed only by the paucity of good data.9 related. Some toxins produce subtle effects, such as the
The American Association of Poison Control Centers “flu-like” symptoms seen with CO poisoning, or cases of
provides annual reports based on data from Regional digitalis overdose, which may mimic intrinsic heart
Poison Centers.10 However, poison center data may not disease. Furthermore, when faced with any known
accurately reflect current reality. Under-representation may overdose, the clinician should also consider agents that
occur in the case of lethal agents, because the majority of have similar effects or may be found on the same shelf in
poisoning deaths never arrive at hospitals (instead, they the bathroom cabinet. That is, with acetaminophen, think
become cases for the medical examiner).11 On the other aspirin; with digitalis, add ß-blockers and calcium-
hand, emergency physicians treat most minor ingestions channel antagonists to the list of suspects.
without consulting a Poison Center. Well-designed forensic
toxicology data are rare. Prehospital Care
There are few well-controlled trials that examine the
Epidemiology And Etiology impact of prehospital care on the poisoned patient. It is
Descriptions of poisonings come to us from ancient times. taken for granted that medics should perform basic
(Some even come from the future. An investigation of the stabilization measures such as providing oxygen when
logs of the Enterprise obtained from the original “Star needed, employing cardiac monitoring for those with
Trek” television series revealed that 35% of the episodes unstable vital signs and cardiotoxic overdoses, and
involved toxin-related incidents.12 These toxic mishaps establishing venous access in those who may require
usually befell the unnamed crew member who had the fluids or life-saving medications. The exact indications
misfortune to beam down with Captain Kirk.) In 1999, for these measures, however, remain unstudied.
over 2.2 million human exposures to toxins were reported Ipecac has generally fallen from favor in the manage-
to the American Association of Poison Control Centers.10 ment of overdoses. It may delay the ultimate administration
Over 75% were reported from the home, and 13% from a of charcoal and has the potential to cause aspiration in those
healthcare facility. Two-thirds of these exposures in- with potential for seizures or depressed mentation.
volved patients less than 20 years of age. The leading At least two clinical trials have studied the efficacy of
agents were cleaning substances (10%), followed by prehospital charcoal administration.18,19 In the first, the
analgesics and cosmetics/personal care products. There average time from first encounter with paramedics to
were 873 poisoning fatalities. The leading fatal agents administration of activated charcoal was 5.0 minutes when
were analgesics, antidepressants, cardiovascular drugs, given in the ambulance, compared to 51.4 minutes when
stimulants, and street drugs. charcoal was delayed until arrival in the ED.18 In the second
Poisoning is an important cause of non-traumatic study, the median time to activated charcoal in the ED was
cardiac arrest in children and young adults.13-15 There are 82 minutes, suggesting that prehospital charcoal administra-
numerous case reports of survival after toxin-induced tion could significantly shorten the time to GI decontamina-
cardiac arrest, often as a result of antidote administration. tion. However, in the vast majority of cases, medics failed to
However, arrest secondary to CO poisoning has an start activated charcoal in the field when indicated.19 (In
especially grim prognosis. One case series examined the fairness to the medics, it is likely that the combination of
outcome of 18 patients who arrested after CO poisoning charcoal plus a careening ambulance could make the emesis
and were initially resuscitated; all died despite adminis- scene from “The Exorcist” seem as refined as an afternoon
tration of HBO.16 tea.) Both studies focused on the timing of charcoal adminis-
tration, and neither examined clinical outcomes.
Pathophysiology In a patient with depressed mental status, paramed-
ics should check the serum glucose and administer
The Renaissance toxicologist Paracelsus opined that any intravenous dextrose when necessary. Hypoglycemia and
substance could be poisonous depending on the dose and overdose are not mutually exclusive. An overdose of
duration of exposure. Once the person is exposed to toxic hypoglycemic agents will, of course, drop the blood
substances, factors such as absorption, distribution, and sugar. Alcohol ingestion may also cause hypoglycemia,
elimination—or “toxicokinetics”—become important. In the especially in children.20
overdose patient, toxicokinetic concepts help interpret the Small doses of naloxone may be required if opiates
Osmolar Gap
When a patient presents with an unexplained metabolic
acidosis, measurement of the osmolar gap may be helpful.
An elevated osmolar gap accompanied by anion gap
acidosis should immediately suggest poisoning by metha-
nol or ethylene glycol.
The osmolar gap is the difference between measured
Figure 1. QRS Widening. serum osmolality (most accurately determined by freezing-
point depression) and the calculated serum osmolality (most
METALACID GAP
Methanol, metformin
Ethylene glycol
Toluene
Alcoholic ketoacidosis
Lactic acidosis
Aminoglycosides, other uremic agents
Cyanide, carbon monoxide
Isoniazid, iron
Diabetic ketoacidosis
Figure 2. Prominent R Wave In Lead aVR. Generalized seizure-producing toxins
ASA or other salicylates
*ECGs courtesy Dr. Russ Kerns. Paraldehyde, phenformin
Table 10. Agents Visible On Abdominal Films. Table 11. Drugs Causing Pneumonitis Or
Pulmonary Edema.
COINS
Chloral hydrate, cocaine packets, calcium MOPS
Opium packets Meprobamate, methadone
Iron, other heavy metals such as lead, arsenic, mercury Opiates, organophosphates
Neuroleptic agents Phenobarbital, propoxyphene, phenothiazines
Sustained-release or enteric coated agents Salicylates, smoke inhalation (including cocaine
smoke), solvents
→
→
→
• Naloxone 2 mg IV or SC (up to 10 • Flumazenil 0.2 mg over 30 seconds,
mg if no response if suspicion of then 0.3 mg q 30 seconds up to a
opioid OD) total dose of 3 mg
• 0.1 mg aliquots in suspected (Class III)
chronic abusers
• Start drip as needed
(Class I-II)
• Wide complex • Sodium bicarbonate 1-2 mEq/kg titrate to QRS narrowing or pH of 7.5-7.55
Yes
tachycardia → • If suspected cocaine, may give lidocaine 1.5 mg/kg followed by 1-4 mg/min drip
with pulse? • Avoid procainamide
(Class II)
→
No
→
The evidenc e for recommenda tions is graded using the following scale. For complete definitions, see back page. Class I: Definitely recommended.
Definitive, excellent evidence provides support. Class II: Acceptable and useful. Good evidence provides support. Class III: May be acceptable,
possibly useful. Fair-to-good evidence provides support. Indeterminate: Continuing area of research.
This clinical pathway is intended to supplement, rather than substitute, professional judgment and may be changed depending upon a
patient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright 2001 Pinnacle Publishing, Inc. Pinnacle Publishing (1-800-788-1900) grants each subscriber limited
copying privileges for educational distribution within your facility or program. Commercial distribution to promote
any product or service is strictly prohibited.
No
→
→
→
• Suspected tricyclic OD: Persistent hypotension: • Suspected or potential
sodium bicarbonate to • Invasive monitoring calcium-channel
achieve pH 7.5-7.55 when feasible blocker or ß-blocker
(Class II) • Consider IABP OD: IV glucagon 2-10
(Class II-III) mg IV followed by drip
if positive response
• Suspected calcium-
channel blocker OD:
calcium chloride 1-3 g
IV slow IV push
(Class II)
No
→
The evidenc e for recommenda tions is graded using the following scale. For complete definitions, see back page. Class I: Definitely recommended.
Definitive, excellent evidence provides support. Class II: Acceptable and useful. Good evidence provides support. Class III: May be acceptable,
possibly useful. Fair-to-good evidence provides support. Indeterminate: Continuing area of research.
This clinical pathway is intended to supplement, rather than substitute, professional judgment and may be changed depending upon a
patient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright 2001 Pinnacle Publishing, Inc. Pinnacle Publishing (1-800-788-1900) grants each subscriber limited
copying privileges for educational distribution within your facility or program. Commercial distribution to promote
any product or service is strictly prohibited.
No
• Polyethylene glycol (1-2 L/h in adults, 25 cc/kg in
Determine the need for whole bowel irrigation:
Yes children) orally or by NG tube (Class III)
• Large ingestions of iron, heavy metals, lithium, → • Continue irrigation until the rectal effluent is clear
and other drugs poorly adsorbed by activated charcoal
(Class III)
• Drug packets (body packers)
→
No
No
→
The evidenc e for recommenda tions is graded using the following scale. For complete definitions, see back page. Class I: Definitely recommended.
Definitive, excellent evidence provides support. Class II: Acceptable and useful. Good evidence provides support. Class III: May be acceptable,
possibly useful. Fair-to-good evidence provides support. Indeterminate: Continuing area of research.
This clinical pathway is intended to supplement, rather than substitute, professional judgment and may be changed depending upon a
patient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright 2001 Pinnacle Publishing, Inc. Pinnacle Publishing (1-800-788-1900) grants each subscriber limited
copying privileges for educational distribution within your facility or program. Commercial distribution to promote
any product or service is strictly prohibited.
Labs?
• Abnormal vital signs
• Altered mental status • Accu-Check
• Symptomatic patient and unknown toxin • Electrolytes (calculate anion gap)
• Ingestion of substance that can produce • Serum osmolality (calculate osmolar gap)
Yes
metabolic acidosis → • ABG
• Possible or known ingestion of toxic alcohol • CPK
• Cyanosis or respiratory distress • Pregnancy test
• Suspected rhabdomyolysis (Class I-II)
• Female of childbearing age
→
No
→
Yes, if:
Toxicology → • Qualitative screen
screen? • Coma with unknown overdose
• Quantitative screen (known or suspected overdose
with APAP, ASA, lithium, theophylline, toxic alcohols,
→
Yes
Need for antidote? → See Table 13
→
No
→
Yes, if:
Dialysis? → Symptomatic patient with ingestion of:
• Isopropanol
→
• Salicylates
• Theophylline (caffeine)
Go to “Clinical Pathway: Disposition Of The Toxicology Patient” • Uremia
• Methanol
• Barbiturates, beta-blockers (water-soluble, such
as atenolol)
• Lithium
• Ethylene glycol
(Class II)
The evidenc e for recommenda tions is graded using the following scale. For complete definitions, see back page. Class I: Definitely recommended.
Definitive, excellent evidence provides support. Class II: Acceptable and useful. Good evidence provides support. Class III: May be acceptable,
possibly useful. Fair-to-good evidence provides support. Indeterminate: Continuing area of research.
This clinical pathway is intended to supplement, rather than substitute, professional judgment and may be changed depending upon a
patient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright 2001 Pinnacle Publishing, Inc. Pinnacle Publishing (1-800-788-1900) grants each subscriber limited
copying privileges for educational distribution within your facility or program. Commercial distribution to promote
any product or service is strictly prohibited.
No
Yes
• Moderately symptomatic → Hospital admission (Class II)
patient with low potential for
fatal outcome?
→
No
No
No
No
The evidenc e for recommenda tions is graded using the following scale. For complete definitions, see back page. Class I: Definitely recommended.
Definitive, excellent evidence provides support. Class II: Acceptable and useful. Good evidence provides support. Class III: May be acceptable,
possibly useful. Fair-to-good evidence provides support. Indeterminate: Continuing area of research.
This clinical pathway is intended to supplement, rather than substitute, professional judgment and may be changed depending upon a
patient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright 2001 Pinnacle Publishing, Inc. Pinnacle Publishing (1-800-788-1900) grants each subscriber limited
copying privileges for educational distribution within your facility or program. Commercial distribution to promote
any product or service is strictly prohibited.
8.“We don’t have a nephrologist at our institution, so we could 10.“I thought the child was okay since she only took one pill.”
not dialyze the patient.” Be careful. There are several toxins that can kill a small
Several potentially life-threatening toxins (e.g., toxic alcohols, child if only one teaspoon or pill is ingested. These
salicylates, lithium) may ultimately require hemodialysis if the include TCAs, methylsalicylate, calcium-channel
patient is in critical condition. If the hospital does not have an antagonists, and hypoglycemic agents. When in doubt,
adequate renal service, the patient may require transfer to assume the worst-case scenario, and admit these patients
another medical center with dialysis capabilities. While for close observation. ▲
Disposition References
Asymptomatic patients with a potentially serious overdose Evidence-based medicine requires a critical appraisal of the
should be observed for 4-6 hours before discharge.159-161 The literature based upon study methodology and number of
six-hour limit may have been based on reports of delayed subjects. Not all references are equally robust. The findings
complications in patients who ingested TCAs.162 Recent data of a large, prospective, randomized, and blinded trial
suggest that the period of observation may be safely should carry more weight than a case report.
shortened in some asymptomatic patients. In one To help the reader judge the strength of each reference,
multicenter study of 260 overdose patients, no patient who pertinent information about the study, such as the type of
was believed to be safe for medical clearance at either two study and the number of patients in the study, will be
or four hours had a complication within the six-hour time included in bold type following the reference, where
period.161 Possible exceptions to this rule may include agents available. In addition, the most informative references cited
with delayed or sustained-release properties such as in the paper, as determined by the authors, will be noted by
calcium-channel antagonists, theophylline, lithium, an asterisk (*) next to the number of the reference.
methadone, Lomotil, MAOIs, and oral hypoglycemics. Since 1. Deichman WB, Henschler D, Holmstedt B, et al. What is there
these overdoses may require prolonged observation, that is not a poison? A study of the Third Defense by
consulting a Poison Control Center may be valuable.163 Paracelsus. Arch Toxicol 1986;58:207-213. (Review)