Toxidromes: Common Poisoning Syndromes to Know

A photo of oxycodone.
A photo of oxycodone. (Photo provided by the authors.)

It was a warm, sunny day when the crew of Rescue 63 responded to a call for a man down. On arrival they found a male in his 50s was lying on the grass in the front of a single-family home. His wife advised that he had been working in the yard immediately prior to the incident.

The crew’s initial impression was that the man was having a heat emergency because his skin was flushed, and he was profusely sweating. That sentiment would quickly change as the initial scene assessment yielded other clues as to the patient’s condition.

Lying on the side of the home near the patient was a sprayer with no markings. This single environmental clue would prove crucial to the determination that the man had issues far greater than exposure to heat.

It was quickly discovered that the sprayer was filled with pesticide that had not been properly diluted. This single fact helped direct their efforts to a combination of patient decontamination in concert with the initial assessment. The crews were able to avoid an exposure and properly treat the patient based on their quick assessment of the scene clues.

Once the hazard was removed and life threats addressed, the patient was noted to have constricted pupils, excessive saliva, wheezing, as well as urinary and fecal incontinence. His pulse was 50, RR 22 and BP 95/50. The signs and symptoms helped in clarifying the patient was suffering from acute exposure to an organophosphate, a key ingredient in the pesticide.

Toxidromes

There are thousands of substances that are toxic to humans and can present with a wide range of signs and symptoms, sometimes progressing to a respiratory or cardiac arrest.

Related

To help with identification, toxins can be grouped based on common presenting physical findings. These groupings are known as “toxidromes.” Recognizing common toxidromes will assist your assessment and treatment of the exposed patients, even when the specific toxin is unknown. Prompt recognition not only leads to better patient outcomes, but also can potentially limit a toxic exposure of the responding emergency responders.

While it is beyond the scope of this article to present every toxidrome, there are six that EMS providers can readily identify and treat. The six toxidromes this article will focus on are: 

  1. Opioid
  2. Cholinergic
  3. Anti-cholinergic
  4. Sedative-Hypnotic
  5. Hallucinogenic
  6. Sympathomimetic

Often, information gathered from the scene will be a critical addition to the patient’s physical findings. Together, this information can guide the initial treatment while also alerting hospital staff of potential hazards for which they will need to be prepared. 

General Considerations for Patient Assessment and Treatment

Rapid recognition of a toxidrome can be of critical importance when establishing scene safety. In most cases, patient poisonings represent no risk to first responders or the public. However, some substances, such as organophosphates, can create a direct threat to care givers and bystanders.

Scene clues such as open containers or spilled liquids near the patient, as well as commercial vehicles with hazardous product markings, can help alert you to the potential risk of self-contamination.

Exposures can be accidental or intentional as is the case when organophosphates are mixed with other commonly available substances by individuals committing chemical suicides in their vehicles.

Chemical suicides, often referred to as detergent suicides, involve self-inflicted exposure to toxic gases in a confined space (for example, cars, bathrooms, or closets), gases created by mixing consumer products or common household chemicals. Three of the most common toxic gases used or produced are organophosphates, hydrogen sulfide and hydrogen cyanide. This is a true hazmat incident.1

Chemical suicides can injure or kill responders and bystanders because a cloud of toxic gas often remains at the scene (the “confined space” inside the vehicle), waiting to be released when a door or window is opened. The materials used in the suicide may continue to off-gas for an extended period after initial generation, and toxic gases may remain in the area for some time.2

If decontamination is warranted, EMS providers should follow local protocols regarding requesting the dispatch of a hazardous materials team, gross decontamination procedures and transport.

After establishing scene safety and the potential need for immediate decontamination, focusing on patient assessment, the standard approach of identifying and stabilizing life-threatening conditions, followed by a head-to-toe assessment, should be followed. Special attention should be paid to the observation of the skin and eyes, as they can provide significant information in the recognition of a toxidrome. Specifically, observe whether the skin is warm or cool, moist or dry, red or pale. The pupils should be observed for miosis (constriction) or myosis (dilation). For example, stimulants can cause profuse sweating with dilated pupils, while an opioid overdose patient’s skin maybe cool and have pin-point pupils. See Table 1.

When obtaining a patient history, the standard SAMPLE format can be used to obtain information about the signs and symptoms the patient is experiencing, either by questioning or direct observation. A history of allergies should be elicited, and it should be determined if the patient is prescribed  (and taking) medications or taking illegal substances.

Past medical history may offer clues as to what medications the patient is likely taking. For example, a patient with a seizure history may be prescribed a barbiturate, and a medication overdose would present with the sedative-hypnotic toxidrome as outlined below.

It is also important to ask about the patient’s last oral intake as well as the events leading up to the incident. Valuable clues are often obtained solely from asking SAMPLE history questions.

Providers should also reach out to the local poison control center for assistance in determining the nature of the substance, the clinical assessment findings, and the treatment for each specific offending agent.

Opioid Toxidrome

EMS providers are generally aware of the opioid toxidrome as there are thousands of calls each year for opiate overdoses. In fact, the opioid crisis has often been described as an epidemic, and the rate of deaths has been increasing dramatically.3-4

These calls often involve heroin, fentanyl, methadone, oxycodone, oxymorphone and a host of other opiate medications.

Opioids depress the central nervous system, and it is expected that the patient will exhibit a decreased level of consciousness, bradypnea, bradycardia, and pinpoint pupils (miosis). The skin will often be dry and there may be evidence of recent injection puncture marks. Scene clues include open pill bottles, syringes with needles, and related drug paraphernalia.

Treatment for patients presenting with an opioid toxidrome is directed at correcting any life threats and administering naloxone (Narcan) as local protocols permit. It may be possible that a family member or first responder administered naloxone prior to EMS arrival.

In the latter case, the field provider must consider whether additional dosing of naloxone is warranted. Since these patients commonly have respiratory depression, high-flow oxygen is often necessary. Continuous waveform capnography and oxygen saturation monitoring are standard in many transport protocols of the patient with an opioid overdose.  

Sedative-Hypnotic Toxidrome

Sedative-Hypnotic drugs cause central nervous system depression and commonly result in somnolence, confusion, ataxia, slurred speech, and when taken in large quantities or mix with other drugs or alcohol, respiratory depression. 

Pupils tend to be mid-sized or constricted, the skin is likely to be dry. The clinical presentation can appear quite like alcohol intoxication.5The most likely encountered sedative hypnotics are the commonly prescribed benzodiazepines. Barbiturates are powerful sedative-hypnotics, but not as commonly found as in the past. In addition, compounds that have been used for drug facilitated sexual assault such as GHB and Rohypnol, have profound sedative-hypnotic effects.

Since the sedative-hypnotic overdoses are easily mistaken for an opioid overdose, it is important to inquire as to prescribed medications and search the scene for pill bottles that may provide clues as to the patient’s toxidrome origin.

You may also be presented with information about the street names that link to the sedative-hypnotic, particularly if the medication was obtained illegally. Common street names and their associated medication name are presented below:

  • Amobarbital: blue heavens, blue devils, blue velvet, downers
  • Pentobarbital: abbots, Mexican yellow, nembies, yellow jackets
  • Phenobarbital: goof balls, purple hearts
  • Secobarbital: F-40s, lily, pinks, pink ladies, red birds, red devils, reds, seggy
  • General street names: barbs, blockbusters, Christmas trees, downers, phennies, sleepers6

Treatment for a sedative-hypnotic toxidrome is directed to correcting life threats and may be limited to supportive care. As these compounds are not active at the opioid receptors, naloxone is not effective in reversing associated respiratory depression.  

While high-flow oxygen may correct the hypoxia associated with depression of the respiratory drive, this may mask hypoventilation and continuous waveform capnography should be considered, where available.   

Cholinergic Toxidrome

Cholinergic agents include medications, such as acetylcholine, methacholine, carbachol, bethanechol, and tacrine.7 Commercial pesticides that include organophosphates can also be toxic. For example, the Environmental Protection Agency (EPA) lists azinphos-methyl (Guthion, Gusathion), bomyl2 (Swat) and carbophenothion (Trithion) as highly toxic.8

Exposure to cholinergic agents or an overdose of a cholinergic medication will often have a classic set of signs and symptoms.9 A popular mnemonic known as “SLUDGE” 10 (or sometimes referred to as “SLUDGEM”) helps to serve as a guide to identifying the underlying issue.

              S: Salivation

              L: Lacrimation

              U: Urinary incontinence

              D: Diaphoresis

              G: Gastrointestinal

              E: Emesis

              M: Miosis

As with the case study that opened this article, there can be a risk of exposure for prehospital personnel if the patient was exposed to certain types of pesticides. It will be critically important to examine the scene for clues, particularly if the individual was working outdoors or in a garage. These small details can be helpful in determining the cause of the toxidrome while concurrently protecting the provider from incidental exposure.

The patient presentation will often involve one or more of the signs and symptoms outlined in the SLUDGE/SLUDGEM mnemonic. Unlike the prior toxidromes presented above, a patient with a cholinergic toxidrome will likely present with diaphoresis. That skin sign may be helpful in differentiating between toxidromes.

As with the opioid and sedative-hypnotic toxidromes, the patient exposed to a cholinergic agent will be expected to present with miosis. Also distinguishing from the opioid toxidrome, cholinergic toxins provoke excessive salivation and wheezing and have the potential to cause seizures.

Treatment for a cholinergic overdose includes attending to any life threats and providing high-flow oxygen. It may be appropriate to administer atropine in dosing directed by local protocols. Pralidoxime Chloride may also be indicated to reverse the effects of the cholinergic agent.

Providers may have access to Mark I Kits (AtroPen Auto-Injector & Pralidoxime Chloride Injector), which contain 2mg of atropine and 600 mg of pralidoxime. These autoinjectors were primarily designed for exposure to weapons grade nerve agents; however, local protocols may allow their use when an EMS caregiver is incidentally exposed to a cholinergic agent, such as an organophosphate.

Hallucinogenic Toxidrome

Marijuana is by far the most-consumed hallucinogenic. The wide prevalence of ingestible forms of cannabinoids has led to a greater number of people seeking medical attention for its hallucinogenic effects. 

Other classic hallucinogenic agents include LSD, psilocybin and mescaline found in certain mushrooms and the chemical DMT, which is found in the South American traditional spiritual brew Ayahuasca.11 Dissociative drugs, which also present with a hallucinogenic toxidrome, include PCP, ketamine and DXM (Dextromethorphan).

Patients exposed to a hallucinogenic substance can present with bizarre symptoms and may induce self-inflicted injury. Fortunately, there is a set of common signs and symptoms that are expressed as the hallucinogenic toxidrome.

Patients with mild to moderate exposure may present with numbness, disorientation, confusion and loss of coordination. Dizziness, nausea, and vomiting are to be expected, and the patient may have changes in sensory perceptions (such as sight, sound, shapes, time and body image) as well as outright hallucinations.

There may be an increase in blood pressure, heart rate, respiration and body temperature. Higher levels of a hallucinogenic agent may present with hallucinations, memory loss, extreme panic, fear, anxiety, paranoia, invulnerability, exaggerated strength and aggression. If the hallucinogenic agent was combined with alcohol, the patient may be found in respiratory or cardiac arrest.

The vital signs may be elevated, and the eyes can display nystagmus or mydriasis. The skin may present as hot and flushed. Scene clues are often of significant importance as these agents are often injected, smoked or ingested as illicit substances.

Treatment for a patient with a hallucinogenic toxidrome requires consideration of the offending agent as well as the clinical presentation. Once the scene is deemed safe, addressing life threats takes precedence. Patients exhibiting severe agitation and aggression benefit from a calm, reassuring, and nonthreatening behavior to “talk down” the patient.

Some patients will require physical restraint and may also need a sedative agent, such as a benzodiazepine or ketamine in accordance with local protocols.

Anticholinergic Toxidrome

The anticholinergic toxidrome presents as the mirror image of the cholinergic-organophosphate toxidrome. These patients have hot, flushed skin, tachycardia and dilated pupils. In addition, they typically present with confusion and delirium.

Anticholinergic agents include antihistamines (Benadryl), anti-Parkinson medications (procyclidine), anti-spasmodics (cyclobenzaprine), and anti-muscarinics (benztropine). There are several species of plants that have anticholinergic toxicity and are occasionally consumed by accident or intentionally to induce hallucinations. These plants include jimson weed, angel trumpet, and deadly nightshade.

Treatment for a patient with an anticholinergic toxidrome is similar to treating a patient with a hallucinogenic toxidrome. Once the scene is deemed safe, address the life threats and provide supportive care.

The lead health care provider can attempt to “talk down” those patients who exhibit severe agitation or aggression. If the patient is found to have excited (agitated) delirium, consider the administration of a benzodiazepine or ketamine in accordance with local protocols.

Sympathomimetic Toxidrome

The sympathomimetic toxidrome is cause by agents that overly stimulate the adrenergic, dopamine or serotonin receptors. Classic medications that stimulate these receptors include epinephrine, nor-epinephrine and dopamine.

Common drugs of abuse of this toxidrome include cocaine, amphetamines and ecstasy, Patients with this toxidrome present with similar findings to the cholinergic toxidrome. They are usually tachycardic, hypertensive, agitated and with dilated pupils. The differentiating finding is the skin. While in the cholinergic toxidrome the skin is dry, the sympathomimetic toxidrome usually causes diaphoresis.

Sympathomimetic toxicity can lead to excited delirium and life-threatening hyperthermia. Pre-hospital treatment includes sedation with benzodiazepines such as lorazepam or diazepam and aggressive cooling techniques. For those agencies with protocols that allow for it, intra-muscular ketamine may be needed to control severely agitated behavior.

Summary

EMS providers are often called upon to manage toxicological emergencies, and toxins can result in a wide array of patient presentations. By learning these six toxidromes presented here, the EMS provider is better able to identify the likely agent or medication involved, the assessment elements, and the treatments that are appropriate for each toxidrome.

References

  1. https://www.chemm.nlm.nih.gov/chemicalsuicide.htm
  2. https://sfist.com/2019/09/01/one-dead-and-multiple-sickened-after-chemical-suicide-in-south-bay-luxury-hotel/
  3. Rudd RA, Aleshire N, Zibbell JE, Gladden RM. Increases in Drug and Opioid Overdose Deaths–United States, 2000–2014. MMWR Morbidity and mortality weekly report. 2016;64(50–51):1378–82.
  4. Lyden J, Binswanger IA. The United States opioid epidemic. Semin Perinatol. 2019 Apr;43(3):123-131. doi: 10.1053/j.semperi.2019.01.001. Epub 2019 Jan 14. PMID: 30711195; PMCID: PMC6578581.
  5. Cooper, Jeffery. Sedative-hypnotic toxicity clinical presentation. Medscape. https://emedicine.medscape.com/article/818430-clinical#b2 Accessed 14 Dec. 2020.
  6. “List Of Barbiturates Prescribed In The United States.” https://www.rehabcenter.net/list-of-barbituates-in-us/ Accessed 14 Dec. 2020.
  7. Pakala RS, Brown KN, Preuss CV. Cholinergic Medications. [Updated 2020 Sep 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538163/
  8. “Organophosphate Insecticides.” https://www.epa.gov/sites/production/files/documents/rmpp_6thed_ch5_organophosphates.pdf Accessed 14 Dec. 2020. 
  9. Lott EL, Jones EB. Cholinergic Toxicity. [Updated 2020 Jun 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-.
  10. Waseem, Muhammad et al. “Cholinergic crisis after rodenticide poisoning.” The western journal of emergency medicine vol. 11,5 (2010): 524-7.
  11. NIDA. 2020, June 2. Common Hallucinogens and Dissociative Drugs. Retrieved from https://www.drugabuse.gov/publications/research-reports/hallucinogens-dissociative-drugs/what-are-dissociative-drugs Accessed on 2020, December 14.
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