- Nov 16th, 2019
- Garrett Christy
Author: Garrett Christy, MD (EM Resident, UTSW) // Reviewed by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital); Kim Aldy, DO, MS, MBA (UTSW Toxicology Fellow); Brit Long, MD (@long_brit, EM Attending Physician, San Antonio, TX)
Welcome to EM@3AM, an emDOCs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.
A 38-year-old male presents from triage in a hospital wheel chair with his head slumped to one side. A nurse calls for help when she tries to wake him up. He appears confused. You immediately move him into bed and assess his ABCs. He wakes briefly, but he seems to be hallucinating and can’t answer any questions.
Vital signs: BP 154/110, HR 110, T 102.1, RR 20, SpO2 100% on room air. Physical exam reveals mydriasis and diaphoresis. He has track marks on his arms and you find packets of what appears to be mixed prescription drugs, heroin, and methamphetamine in his pocket. Review of the EMR shows that the patient has a significant psychiatric history and prior suicide attempts.
What’s this presentation most consistent with? What’s your next step in evaluation and treatment?
Answer: Sympathomimetic syndrome vs. Anticholinergic syndrome.
Background: Toxicity from ingested substances occurs when a patient is exposed to an amount of drug that is greater than what is recommended, or if multiple similar acting medications are used. According to the CDC there were over 70,000 deaths in 2017 due to drug overdose. Sixty-seven percent were opioid related. The rest included use of psychostimulants and polysubstance abuse.
- Emergency physicians are on the front lines and battle the devastating effects of drug abuse on a daily basis.
- There are approximately 1.2 million overdose related ED visits per year in the United States and 120 deaths per day.
- Approximately two-thirds are related to prescription medications obtained from friends or family members.
Thankfully, about 60% of patients presenting for overdose are discharged home.
- The pharmacology of a general overdose is best understood in terms of “Toxicokinetics”, a term meant to denote that the pharmacokinetics we understand about a particular drug or formulation do not apply at the extreme levels of drug exposure during an overdose. In other words, the absorption, distribution, metabolism, and elimination are unpredictable.
- Specific pharmacologic and pathophysiologic effects will be dependent on the agents involved and the route of exposure (e.g. enteral or parenteral).
- Some of the most common drugs involved in overdoses in the US fit into symptom complexes called toxic syndromes or “toxidromes”. These toxidromes can be recognized through analyzing patterns of physical exam findings and vital signs as indicated in the table below.
Courtesy of Kim Aldy, DO, UT Southwestern Toxicology Fellow
- Sympathomimetic (uppers): Cocaine, methamphetamine, MDMA, PCP, ephedrine, pseudoephedrine, synthetic cannabinoids (K2) and cathinones (bath salts)
- Opioid: Morphine, hydrocodone, oxycodone, fentanyl, carfentanyl, methadone, loperamide
- Cholinergic: Organophosphates and carbamates
- Anticholinergic: Diphenhydramine, benztropine, TCAs, many antipsychotics, atropine, dicyclomine
- Serotonergic: SSRIs, SNRIs, TCAs, MAOIs, buspirone, antipsychotics, lithium, meperidine, tramadol, triptans, cough medicine (e.g. dextromethorphan), linezolid, cocaine
- Sedative-hypnotic (downers): Benzodiazepines, barbiturates, zolpidem
- Neuroleptic: Haloperidol, risperidone, olanzapine, etc.
- Miscellaneous toxic drugs: Acetaminophen, ASA, anti-hypertensives (BBs/CCBs), sulfonylureas, iron pills
- History is often difficult so try to get information early or from friends and family if present. Try to obtain the following:
- Drug name and formulation? (Do they have a bottle? Is it extended release?)
- Time of exposure?
- Route of exposure?
- Amount of drug?
- Acute or chronic exposure?
- Prior drug overdose?
- Patient medical conditions and daily medications or supplements?
- Medications in the home?
- Intentional/Unintentional? (NB: If intentional, you should check salicylate and APAP level because co-ingestions are common.)
- It may also be helpful to conduct a chart review in the EMR to determine prior history of drug use or hospitalizations.
- Prioritize assessment and management of the patient’s ABCs.
- As you begin your physical exam ensure to remove clothing carefully, as you may encounter used needles.
- Obtain a full set of vital signs
- Temperature: Hypothermia is common in patients “found down”, whereas hyperthermia could indicate ASA, NMS, Serotonergic, or Sympathomimetic drug exposure.
- Blood pressure: SBP can be low (antihypertensives) or elevated (sympathomimetics)
- Pulse: Tachycardia (anticholinergics, serotonergics), Bradycardia (cholinergics)
- Respiratory rate: bradypnea (opioids), tachypnea (ASA)
- Pulse oximetry (e.g. 85% may indicate methemoglobinemia)
- EtCO2 for suspected sedative, opioid toxicity
- Normal vitals in a comatose patient may indicate a sedative hypnotic exposure.
- Focus the remainder of your exam with special attention to detecting specific toxidromes.
- HEENT: Miosis? Mydriasis? Roving eye movements? Excess tear or saliva production? Hearing difficulty/tinnitus?
- Chest/CV/Lungs: Wheezing? Rhonchi? Bradycardia or Tachycardia? (Look out for the Killer B’s of cholinergic excess: bronchorrhea, bradycardia, & bronchospasm).
- Abdomen: Absent bowel sounds?
- Skin: Dry? Diaphoretic? Track marks?
- Neurologic: Reflexes? Muscle Tone? Rigidity may indicate NMS. Myoclonus/hyperreflexia = Serotonin syndrome
- Psychiatric: Hallucinations? Agitation? Pleasant hallucinations occur with anticholinergic syndrome. Agitated delirium may indicate sympathomimetic syndrome.
- Initial labs may include POC glucose, CBC, CMP, ABG, coagulation panel, CK, lactate, TSH, 4-hour acetaminophen level, salicylate level (usually requires repeat if not negative to ensure it is not increasing), EtOH level, and urinalysis +/- UTox.
- US: if concerned for abscess, foreign body (needle), pulmonary edema; RUSH exam if patient presents in undifferentiated shock
- CXR: if respiratory dysfunction, secretions, or to detect radiopaque foreign body (e.g. iron pills)
- EKG in all overdoses
- Pay particular attention to prolonged QRS and QT intervals (QRS > 100 msec may need immediate therapy with sodium bicarbonate, or QTc > 500 msec may need magnesium replacement)
- Look for typical EKG changes consistent with suspected exposure (e.g. terminal R wave in aVR for TCA overdose)
Start with supportive care and resuscitation. Consider activated charcoal if not contraindicated.
Depending on the suspected agent, it may be prudent to consult Poison Control or a toxicologist early for proper treatment prior to decompensation.
- Opioid: Pinpoint pupils, bradypnea –Trial of Narcan (Start at 0.04 mg IV/IM, titrated to RR as higher doses may precipitate withdrawal, but may start higher if peri-arrest) Read more: Narcan
- Anti-hypertensives: Hypotension + Bradycardia – IVF bolus, glucagon 5-10 mg (always give antiemetics first!), high dose insulin euglycemia therapy starting at 1U/kg/hr, & pressors. Read more: BB overdose
- Anticholinergic: Pleasant hallucinations, HTN, tachycardia, flushed and dry skin – benzodiazepines, 1-2 amps of sodium bicarbonate pushed if QRS > 100 msec while watching for narrowing, may repeat if effective. Learn more: Anticholinergic
- Cholinergic: DUMBBBELLS mnemonic – Atropine 0.02 mg/kg IV (double every 2-3 minutes titrated to cessation of secretions) and Pralidoxime (2-PAM) 30 mg/kg IV; benzodiazepines for seizures. Read more: Cholinergic syndrome
- Sympathomimetic: Agitation, HTN, tachycardia, diaphoresis – Benzodiazepines, avoid beta-blockers. Read more: Sympathomimetic toxidrome
- APAP: Can be asymptomatic – draw 4-hour level and use Rumack-Matthew nomogram. If indicated give NAC IV (21 hour, 3 bag regimen) Read more: APAP Overdose
- Salicylate: AKA “pseudosepsis” – ASA level > 20 mg/dL, respiratory alkalosis, metabolic acidosis, hyperventilation, hyperthermia, tinnitus – avoid intubation if possible, Sodium bicarbonate for urine alkalinization with goal urine pH > 7.5. Read more: Salicylate Toxicity
- Unsure: If mixed or unsure and the patient is crashing/coding, may try Intralipid therapy. Dose- Bolus 1.5 mL/kg 20% Intralipid Read more: Intralipid Rescue
- Serotonin syndrome/NMS: physical exam findings are similar, but SS exhibits myoclonus and hyperreflexia (Treatment is cyproheptadine, but exists as an oral formulation. Benzos should be tried first.); NMS exhibits rigidity (treatment is IVF and external cooling; bromocriptine if severe). Read more: SS vs. NMS
- Take into account the half-life of the drug, unstable vital signs, and anticipated clinical course.
- If unstable, resuscitate and admit for cardiorespiratory monitoring.
- If stable but exposed to extended release or substance known to from bezoar (ASA), may admit to ED observation unit.
- Opioid overdose that has been successfully reversed with Narcan may be safe for discharge in 2-4 hours, although traditionally these patients have been watched for 4-6 hours after last dose.
Take home points:
- Consider consultation with a toxicologist in most cases (1-800-222-1222).
- Most initial therapy is supportive rather than having a specific antidote; however toxicology is largely about anticipation of symptoms that may occur (such as seizures) to prevent decompensation.
- When in doubt, initiate traditional resuscitative measures and ACLS.
From Dr. Katy Hanson at Hanson’s Anatomy:
For which toxicologic overdose is urinary alkalinization a mainstay of management?
A) Acetaminophen toxicity
B) Carbamazepine toxicity
C) Iron toxicity
D) Salicylate toxicity
Decontamination has traditionally been used in the setting of toxicologic overdose, and methods vary from irrigation, gastric decontamination, urinary alkalinization, and extracorporeal removal. The type of decontamination technique employed depends on the substance involved, the risks and benefits to the patient, the likelihood that the agent is going to lead to significant toxicity, and whether use of the decontamination technique will improve clinical outcomes. Alkaline urine ionizes acidotic drugs within renal tubules, prevents resorption of the ionized drug back across the renal tubular epithelium, and enhances elimination through the urine. It is most effective for weak acids, primarily those eliminated by the renal tract. The primary indication for urinary alkalinization is moderate to severe salicylate toxicity. Sodium bicarbonate is the essential component of management of the salicylate poisoned patient. A bolus should be administered followed by an infusion to maintain urine pH between 7.50 to 8.0.
Decontamination of acetaminophen toxicity (A) is usually through activated charcoal, but the evidence is limited on improved clinical outcomes. Activated charcoal is recommended for patients with a significant ingestion and presentation to the emergency department within one hour of overdose. Recommendations for decontamination of carbamazepine toxicity (B) include enhanced elimination with multidose activated charcoal. Multidose activated charcoal increases elimination of toxins with enterohepatic, enteroenteric, or enterogastric recirculation. Animal and volunteer studies demonstrate increased elimination rates of carbamazepine, but there is limited evidence that it changes clinical outcomes in humans. Iron toxicity (C) can potentially be managed with whole bowel irrigation but patients rarely tolerate whole bowel irrigation and, again, evidence is limited on improved clinical outcomes. Urinary alkalinization will not affect iron metabolism.
- Goldfrank LR, Nelson L. Goldfranks Toxicological Emergencies. New York: McGraw-Hill Medical; 2011.
- Opioid Overdose. Centers for Disease Control and Prevention. https://www.cdc.gov/drugoverdose/data/otherdrugs.html. Published May 2, 2019. Accessed June 16, 2019.
- Drug Abuse. American College of Emergency Physicians | News Room. http://newsroom.acep.org/2009-01-04-drug-abuse-fact-sheet. Accessed June 20, 2019.
- Mityanand Ramnarine R, Ahmad DA. Anticholinergic Toxicity Treatment & Management: Prehospital Care, Emergency Department Care, Consultations. Medscape. https://emedicine.medscape.com/article/812644-treatment. Published February 5, 2019. Accessed July 16, 2019.
- The Acetaminophen Toxicity Equations: “Solutions” for Acetaminophen Toxicity Based on the Rumack-Matthew Nomogram White, Steven J.Rumack, Barry H. et al. Annals of Emergency Medicine, Volume 45, Issue 5, 563 – 564
- Sangani A. Neuroleptic Medications. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK459150/. Published October 27, 2018. Accessed July 15, 2019.
- Clemency BM, Eggleston W, Shaw EW, et al. Hospital Observation Upon Reversal (HOUR) With Naloxone: A Prospective Clinical Prediction Rule Validation Study. Academic Emergency Medicine. 2018;26(1):7-15. doi:10.1111/acem.13567.
- Hayley Kateon (2013) Differentiating serotonin syndrome and neuroleptic malignant syndrome. Mental Health Clinician: September 2013, Vol. 3, No. 3, pp. 129-133.