CONTENTS
- History
- Exam
- Labs
- EKG
- Other diagnostic interventions
- Management
- Podcast
- Questions & discussion
- Pitfalls
- Toxicology histories are notoriously unreliable.
- Key bits of information:
- Any available medical records, especially medication lists.
- Timing & amount of ingestions.
- 🔑 Immediate vs. sustained-release formulations.
- Consider inquiring specifically about the ingestion of acetaminophen or acetaminophen-containing combination pills (e.g., over the counter sleep aids, or combination cold remedies).
- Collateral information from first responders, family, and pharmacies may help.
- In general, histories should be used only to broaden the differential diagnosis, rather than to narrow it:
- If the patient doesn't recall taking something, that doesn't exclude it with certainty.
- If the patient reports taking something, that is a likely intoxicant (although this doesn't exclude coingestions).
pay particular attention to the following:
Constellations of findings (toxidromes) aren't completely reliable, but it can help focus the differential diagnosis. In complex polysubstance intoxications, toxidromes can become jumbled together.
among patients who are comatose or obtunded:
- Additionally, perform a coma neurological examination (figure below; more on this here).
- If a focal neurologic deficit is present, this shouldn't be attributed to intoxication. Rather, neuroimaging should be considered to exclude a focal anatomic abnormality (e.g., intracranial hemorrhage).
For a critically ill intoxicated patient, history is often unreliable and time is of the essence. Therefore, a relatively broad set of laboratory tests may be reasonable.
labs to obtain in most critically intoxicated patients
- Fingerstick glucose (as for anyone with altered mental status).
- Electrolytes including Ca/Mg/Phos.
- Complete blood count with differential.
- Liver function tests.
- Lactate. (the differential diagnosis of hyperlactatemia is here)
- Acetaminophen & salicylate levels.
- Pregnancy test if appropriate.
additional labs to consider
- Coagulation studies.
- Creatine kinase (if concern for rhabdomyolysis due to prolonged coma or seizures).
- Ethanol level (if evidence or suspicion of inebriation).
- Medication levels if the patient is known or suspected to be exposed to them (carbamazepine, digoxin, lithium, methotrexate, phenobarbital, phenytoin, theophylline, valproic acid).
- Carboxyhemoglobin level if possible exposure to carbon monoxide (note that this can be measured using venous blood).
why this is generally unhelpful
- (1) Clinical false-positives:
- Prescription pharmaceuticals often cross-react with the urine toxicology panel, generating false-positive results. A positive urine toxicology result should ideally be submitted for confirmatory testing (e.g., using gas chromatography/mass spectroscopy). However, these results will not return in time to affect patient management.(28325505)
- A positive result may reflect recent exposure, rather than acute intoxication. Although this is technically an accurate result, it may be clinically misleading. For example, a patient who used cocaine yesterday may present with an epidural hematoma due to trauma. The urine toxicology will be positive for cocaine, but that has nothing to do with the patient's active issue.
- (2) False-negatives
- Urine toxicology panels often test for a few common substances, while ignoring others. Innumerable intoxicants will elude common toxicology panels (e.g., fentanyl, oxycodone, alprazolam, clonazepam, lorazepam, synthetic cathinones, synthetic cannabinoids).
- The drug level may be below the threshold of detection of the assay. Overall, the urine toxicology panel may occasionally stumble upon useful information, but it will often provide misleading information as well. Available evidence suggests that the urine toxicology panel doesn't add significantly to the clinical gestalt based upon evaluation of other data.
- 💡 For a test to be helpful, it's doesn't just need to be somewhat accurate. It needs to be more accurate than clinical assessment in the absence of the test!
potential causes of false-positive urinary toxicology results
- Note: Different assays may vary, depending on the cutoff thresholds utilized. The lists below are intended merely to provide a general conception of potentially interacting substances. In some cases, these are based on only a few case reports of dubious veracity.(32843202, 30600984)
- Amphetamine: Amantadine, aripiprazole, atenolol, atomoxetine, benzphetamine, bupropion, chlorpromazine, chloroquine, desipramine, doxepin, ephedrine, isometheptene (component of Prodrin), labetalol, levomethamphetamine, MDMA, metformin, methylphenidate, phentermine, phenylephrine, promethazine, pseudoephedrine, propranolol, ranitidine, selegiline, thioridazine, trazodone, trimipramine, trimethobenzamide.
- Barbiturates: Ibuprofen, naproxen.
- Benzodiazepines: Efavirenz, oxaprozin, sertraline.
- Buprenorphine: Codeine, methadone, morphine, tramadol.
- Cocaine: This is specific for cocaine – the most accurate test on the urine toxicology report.
- LSD: Amitriptyline, bupropion, buspirone, diltiazem, doxepin, ergonovine, fentanyl, fluoxetine, haloperidol, imipramine, labetalol, methylphenidate, metoclopramide, norfentanyl, prochlorperazine, risperidone, sertraline, trazodone, verapamil.
- Methadone: Diphenhydramine, doxylamine, quetiapine, tapentadol, verapamil.
- Opioids (morphine/codeine/heroin): Dextromethorphan, diphenhydramine, doxylamine, fluoroquinolones, imipramine, levofloxacin, naltrexone, ofloxacin, poppy seeds, quinine, rifampin, verapamil.
- PCP: Dextromethorphan, diphenhydramine, doxylamine, ibuprofen, imipramine, ketamine, lamotrigine, meperidine, thioridazine, tramadol, venlafaxine, zolpidem, some synthetic cathinones.
- THC: dronabinol, efavirenz, rarely NSAIDs, pantoprazole, promethazine.
- Tricyclic antidepressants: Carbamazepine, cetirizine, cyclobenzaprine, cyproheptadine, diphenhydramine, hydroxyzine, quetiapine.
- ⚠️ Although these substances aren't tricyclics, many of them do have sodium channel blockade properties – so they may have similar toxicity (e.g., carbamazepine, cyclobenzaprine, diphenhydramine). More on sodium channel blocker toxicity here. The EKG is the best evaluation of sodium channel blockade toxicity.
- 🔑 An EKG should be obtained in all patients. In addition to a complete evaluation of the EKG, pay special attention to the following aspects:
- (#1) Sodium channel blockade may be revealed by QRS widening, a tall R-wave in aVR, and occasionally a Brugada pattern in V1 (more on these findings here). If this is found, consider administration of hypertonic bicarbonate followed by a second EKG. Improvement in the EKG with hypertonic bicarbonate supports the diagnosis of sodium channel blocker intoxication.
- (#2) Potassium channel blockade may be revealed by predominant widening of the QTc. A QTc interval greater than ~500 ms may increase the risk of torsade de pointes. Aggressively replete potassium and possibly consider administration of extra magnesium (more on torsade de pointes here).
- Intoxication doesn't exclude head trauma or meningitis.
- For patients with altered mental status, further tests (e.g., CT head, LP) may be warranted, depending on the context.
- When in doubt, serial observation can be helpful. Patients with intoxication will often clear over time, indicating that invasive testing may be unnecessary (e.g., lumbar puncture). Likewise, close attention to the fever curve may provide additional information about the risk/benefit ratio of lumbar puncture.
should all patients with intoxication and low GCS be intubated?
- Traditional dogma is that a GCS (Glascow Coma Score) below 8 is an indication for intubation (“GCS below eight, intubate!”). This is now known to be incorrect.(33226502) Published series have shown that intoxicated patients with low GCS may do fine without intubation. Alternatively, a GCS of eight or greater is no guarantee that the patient will not deteriorate and require intubation.
- The decision regarding intubation is much more complicated than an arbitrary GCS cutoff.
key factors to consider regarding intubation
- Intubation is always a clinical decision which is rendered at the bedside. The following are some factors which may be helpful to consider.
- (1) Availability of an antidote:
- If hypoglycemia is known or suspected, IV dextrose should be given immediately.
- If opioid intoxication is suspected, naloxone should be given immediately (more on this here).
- If anticholinergic toxidrome is present, physostigmine may be considered (more on this here).
- Response to an antidote may occasionally abrogate the need for intubation, most commonly in the case of opioid intoxication.
- (2) Inadequate airway protection:
- Inadequate airway protection is also an indication for intubation. Unfortunately, assessing “airway protection” is more of an art than a science.
- Assessment of the gag reflex is not helpful. Although commonly employed, this practice should be abandoned.
- The best evidence for airway protection is an intact swallow reflex, which can occasionally be observed incidentally at the bedside.
- Secretions pooling in the airway indicate inadequate airway protection, whereas a robust cough is reassuring.
- (3) Failure of oxygenation or ventilation:
- Severe failure of oxygenation and/or ventilation, in the absence of an immediately reversible cause, is an indication for intubation in the context of an intoxicated patient.
- 💡 Mild hypercapneic acidosis may be clinically observed if the patient is protecting their airway and otherwise doing well clinically. This isn't necessarily an indication for either intubation or BiPAP. Treat the patient, not the blood gas!
- (4) Clinical trajectory:
- When intubation isn't obviously needed, a wise approach may be to wait and watch carefully.
- If the patient's mental status is gradually clearing, then ongoing observation is best. Alternatively, if the mental status is progressively deteriorating over time, then intubation may be wise.
- In some intoxications (e.g., tricyclic antidepressants), patients may deteriorate rapidly and unexpectedly – so it may be rational to pursue airway control earlier than usual.
- (5) Need to expedite additional testing or transportation:
- Patients with dubious airway control may be unsafe to transport out of the department (especially if an MRI scan is needed, or interhospital transport is required).
- In some situations, intubation is necessary to logistically expedite testing (e.g., lumbar puncture, advanced imaging).
- (6) Number & trajectory of organ failures:
- The number of failing organs can be used as a rough gauge for how likely the patient is to deteriorate and require intubation.
- The presence of multiorgan failure increases the likelihood that the patient will deteriorate and favors intubation (e.g., poor mental status plus worsening hypoxemia plus deteriorating blood pressure).
general principles
- Benefits from charcoal are largely limited to the immediate post-ingestion period (e.g., within ~1 hour of ingestion).
- Charcoal should never be given to a nonintubated patient with altered mental status or with another instability that suggests a risk of requiring imminent intubation.
- Intubation should never be performed to facilitate the administration of charcoal.
reality of activated charcoal administration
- 🦄 Theoretically, charcoal should be given to patients who present <1 hour after intoxication and who have a normal mental status. Realistically, this scenario rarely occurs, since patients generally present well outside of this time window.
- It is reasonable to give a dose of activated charcoal to any patient who requires intubation due to intoxication (e.g., immediately following intubation).
evaluate for the cause of agitation
- The best treatment of agitation is always to eliminate the cause (if possible).
- Patients with anticholinergic toxicity may have bladder distension – this responds to Foley catheter drainage.
- Patients with trauma may have pain – treat their pain.
- For patients with mild agitation, providing food may be helpful.
medical therapy
- For extreme agitation which poses an immediate life-threat: Consider ketamine dissociation (e.g., 1.5 mg/kg IV or ~5-7 mg/kg IM).
- For moderately severe agitation: Consider an antipsychotic (e.g., 10 mg droperidol IM or 10 mg olanzapine IM/IV). A somewhat smaller dose of antipsychotic plus midazolam may accelerate the effect, at the cost of a slight increase in respiratory suppression (e.g., 5 mg droperidol plus 5 mg midazolam).
- For mild agitation: A benzodiazepine is a reasonable choice (which may help reduce the risk of seizure). A smaller dose of antipsychotic is another option (e.g., 5 mg IV haloperidol).
- A dexmedetomidine infusion can be helpful for recurrent or difficult-to-treat agitation, since it is titratable and doesn't suppress respirations. The primary contraindications to dexmedetomidine are bradycardia, heart block, or hypotension. A dexmedetomidine infusion takes a while to work, so it might be initiated concurrently with one of the above therapies (with plans to use the dexmedetomidine as ongoing maintenance therapy for agitation).
avoid physical restraints
- Physical restraint may be needed initially, to protect the patient and staff from harm. However, the goal is always to calm the patient chemically – with discontinuation of restraints as early as possible.
- Physical restraints may promote rhabdomyolysis and hyperthermia, which may push some patients down a vicious spiral of seizures & hyperthermia.
- (#1) Exclude or treat hypoglycemia:
- Check a finger stick glucose to exclude hypoglycemia.
- If the glucose isn't immediately known or if the finger stick glucose is borderline, administer IV glucose empirically.
- (#2) Consider a naloxone trial:
- Naloxone may be tried, especially if there is suspicion for opioid intoxication (e.g., based on a low respiratory rate or miotic pupils).
- For patients who aren't at imminent risk from hypoventilation, small doses should be used initially (e.g., ~0.1 mg) with gradual up-titration to a total cumulative dose around ~5-10 mg.
- More on naloxone for opioid intoxication here.
- (#3) IV Thiamine administration is reasonable if Wernicke's encephalopathy is possible (e.g., 500 mg IV).
- More on the initial approach to the comatose or obtunded patient here.
- Hyperthermia may be defined as a core temperature above roughly ~40-41C (~104-105.8 F).
- Hyperthermia is a medical emergency in the context of intoxication, since it may promote seizures, rhabdomyolysis, and hepatic failure (the hyperthermia-seizure-death vortex).
- Hyperthermia will not usually respond to antipyretic therapy (e.g., acetaminophen), since it reflects excess thermal energy (rather than hypothalamic dysfunction).
- Controlling hyperthermia depends on physical cooling, which may include one or more of the following (depending on available resources and the severity of the hyperthermia):
- Resuscitation with refrigerated crystalloid.
- Evaporative cooling (spray lukewarm water and fan the patient's body).
- Ice packs.
- Immersive ice bath, or packing the patient in ice.
- In the most severe cases (e.g., with seizure or coma) – intubation with depolarizing paralytic, combined with the above techniques.
- More on the treatment of hyperthermia here.
common causes of toxicological seizures
- Antidepressants (bupropion, citalopram, tricyclics, venlafaxine).
- Hydrazines (isoniazid or Gyromitra mushrooms).
- Lithium.
- Sodium channel blockers (e.g. diphenhydramine, tricyclic antidepressants).
- Sympathomimetics (e.g., amphetamines, cocaine, MDMA).
- Tramadol.
- Withdrawal (e.g., ethanol, benzodiazepine, baclofen).
acute management of convulsive status epilepticus
- Benzodiazepine is the front-line treatment, for example:
- Lorazepam 0.1 mg/kg IV.
- Midazolam 10 mg IV/IM.
- Hypoglycemia or hyponatremia should be treated immediately, if present.
- Hyponatremia may be immediately managed with two ampules of hypertonic sodium bicarbonate (for a total of 100 mEq in 100 ml). 📖
- Second-line treatment for ongoing convulsive status epilepticus is arguably induction of anesthesia with ketamine and propofol, followed by intubation. After intubation, a propofol infusion may be used to provide sedation and prevent seizure recurrence. An antiepileptic agent should generally be added as well. More on convulsive status epilepticus: 📖
antiepileptic agent
- An antiepileptic agent isn't necessarily needed for every patient with a toxicological seizure. For example, if the cause of the seizure is being treated, that may be adequate (e.g., hypertonic bicarbonate administered for sodium channel blocker intoxication).
- ⚠️ Phenytoin is contraindicated in toxicological seizures. Phenytoin has class Ib antiarrhythmic activity, which may aggravate the sodium blocking effect of some intoxications.
- The primary choice is usually between phenobarbital vs. levetiracetam:
- Phenobarbital is a good option, especially for seizures due to withdrawal of ethanol, benzodiazepines, or barbiturates. A dose of ~15-18 mg/kg should provide antiepileptic activity, while simultaneously treating the withdrawal syndrome. 📖 The drawback of phenobarbital is that it may cause sedation.
- Levetiracetam is a reasonable choice of antiepileptic agent.(28753046). Levetiracetam appears to be a safe choice, but its efficacy for toxicology-related seizures remains difficult to prove.
specific situations
- Sodium channel blocker poisoning should be treated with hypertonic bicarbonate. 📖
- Isoniazid overdose or Gyromitra mushroom poisoning should be treated with high-dose IV pyridoxine (e.g., 5 grams).🍄
- Toxicological bradycardia may be refractory to standard Advanced Circulatory Life Support (ACLS) protocols. For example, such protocols often lack intravenous calcium. Considerations here include the following:
- (#1) Bradycardia due to digoxin poisoning requires specific antidotal therapy as described here. This may be suggested by EKG findings of digitalis effect, by known exposure to digoxin, or by known exposure to plants containing cardiac glycosides.
- (#2) When in doubt, consider empirically treating the patient as if they have a calcium channel or beta-blocker intoxication (this resuscitative pathway is outlined here).
- This pathway includes all of the possible treatments for toxicologic bradycardia (other than digoxin-neutralizing antibody fragments).
- Hypoglycemia may suggest beta-blocker poisoning, whereas hyperglycemia suggests calcium channel blocker intoxication. However, you don't need to reach a specific diagnosis, because the treatment of either intoxication is largely the same.
is it truly ventricular tachycardia?
- Agents that block the sodium channel may prolong the QRS interval, leading to a wide-complex sinus tachycardia. If this is suspected, hypertonic bicarbonate should be administered (as described here). Narrowing of the QRS complex in response to sodium bicarbonate supports the diagnosis of sodium channel blocker toxicity.
treatment of monomorphic ventricular tachycardia
- Treatment of monomorphic ventricular tachycardia is different from non-toxicologic patients, for example:
- Procainamide should be avoided (if the patient ingested an agent with sodium channel blocking properties, the procainamide will make matters worse).
- Amiodarone may not be a terrific choice (in patients with QT prolongation, amiodarone will cause further prolongation).
- Treatments which may be more helpful include:
- Lidocaine is somewhat unique among antiarrhythmics in that it doesn't prolong the QTc or QRS intervals. Lidocaine can be beneficial in intoxications which inhibit the sodium and/or potassium channels.
- Hypertonic sodium bicarbonate (e.g., ampules of sodium bicarbonate) is essential if the poisoning involves an agent blocking the sodium channel.
- When in doubt, treating the patient as if they have monomorphic ventricular tachycardia due to a sodium channel blocker may provide a useful treatment pathway (more on this here).
- It is generally advisable to discuss complicated cases with poison control (1-800-222-1222 in the US) or a local toxicologist.
- A good time to do this is generally once the dust has settled a bit. Secondary review of the case may reveal issues which were overlooked initially.
- Contact information:
- United States: 1-800-222-1222
- Phone numbers for international poison centers are here.
Follow us on iTunes
To keep this page small and fast, questions & discussion about this post can be found on another page here.
- Be careful about “satisfaction of search” – just because you determine that the patient took one drug doesn't mean that they didn't take multiple agents. Likewise, just because the patient is intoxicated doesn't mean that they don't have a simultaneous traumatic injury.
- “Treat the patient, not the toxin” – when in doubt, the best management generally consists of high-quality supportive care. Don't get too distracted by toxicological fanciness.
Guide to emoji hyperlinks
- = Link to online calculator.
- = Link to Medscape monograph about a drug.
- = Link to IBCC section about a drug.
- = Link to IBCC section covering that topic.
- = Link to FOAMed site with related information.
- = Link to supplemental media.
References
- 28325505 Moeller KE, Kissack JC, Atayee RS, Lee KC. Clinical Interpretation of Urine Drug Tests: What Clinicians Need to Know About Urine Drug Screens. Mayo Clin Proc. 2017 May;92(5):774-796. doi: 10.1016/j.mayocp.2016.12.007 [PubMed]
- 28753046 Lee T, Warrick BJ, Sarangarm P, Alunday RL, Bussmann S, Smolinske SC, Seifert SA. Levetiracetam in toxic seizures. Clin Toxicol (Phila). 2018 Mar;56(3):175-181. doi: 10.1080/15563650.2017.1355056 [PubMed]
- 30600984 Kale N. Urine Drug Tests: Ordering and Interpreting Results. Am Fam Physician. 2019 Jan 1;99(1):33-39 [PubMed]
- 32843202 Stellpflug SJ, Cole JB, Greller HA. Urine Drug Screens in the Emergency Department: The Best Test May Be No Test at All. J Emerg Nurs. 2020 Nov;46(6):923-931. doi: 10.1016/j.jen.2020.06.003 [PubMed]
- 32981621 Skolnik A, Monas J. The Crashing Toxicology Patient. Emerg Med Clin North Am. 2020 Nov;38(4):841-856. doi: 10.1016/j.emc.2020.06.014 [PubMed]
- 33226502 Mégarbane B, Oberlin M, Alvarez JC, Balen F, Beaune S, Bédry R, Chauvin A, Claudet I, Danel V, Debaty G, Delahaye A, Deye N, Gaulier JM, Grossenbacher F, Hantson P, Jacobs F, Jaffal K, Labadie M, Labat L, Langrand J, Lapostolle F, Le Conte P, Maignan M, Nisse P, Sauder P, Tournoud C, Vodovar D, Voicu S, Claret PG, Cerf C. Management of pharmaceutical and recreational drug poisoning. Ann Intensive Care. 2020 Nov 23;10(1):157. doi: 10.1186/s13613-020-00762-9 [PubMed]