Toxidromes are defined as signs and symptoms associated with toxicity from a class of drugs (eg, opiate, cholinergic, etc). When assessing the unknown overdose patient, a common challenge is obtaining a coherent history either from the patient, his or her relatives, or from first responders. The key elements in the toxicology history include what medications or substances were ingested; the amount ingested, and/or the concentration if applicable; the time of ingestion; whether emesis occurred and if pill fragments were noted by the patient or other persons at the scene; and the reasons why the patient ingested the substance. Was this a suicide attempt, recreational use, accidental, or malicious?
Determining the patient's current symptoms is also helpful in defining a possible toxidrome and assists in management. Common toxidromes to consider include opiate, sympathomimetic, anticholinergic, cardiovascular, and anticholinergic (See Table 98-1). Looking for signs and symptoms of serotonin and neuroleptic malignant syndromes is also important in the management and disposition of these patients.
Table 98-1 Identifying Common Toxidromes ||Download (.pdf)
Table 98-1 Identifying Common Toxidromes
|Mental Status||Vital Signs||Pupils||Skin|
Key points in the toxicology history of ingestions
The toxicology history “MATTERS”
- Medication or substances ingested
- Amount ingested
- Time the medication was taken
- Toxicology of drug
- Emesis and presence of pill fragments
- Reasons for injestion
- Signs and Symptoms
The physical examination findings in overdosed and poisoned patients may rapidly change. The mental status, vital signs, pupil size, and skin are important; and in some case, odors can point to the diagnosis. The mental status may range from severe somnolence to extreme agitation or hallucinations. It is important to note whether the vital signs are elevated, normal, or depressed. Pupils are typically reported as (Pupils Equal Round React to Light and Accomodate) “PERRLA” without reporting size. Whether the pupils are pinpoint, mid-size, or large may help with distinguishing the toxidrome. Skin changes may not be immediately noted, but specifically look for findings such as flushing or cyanosis, diaphoresis or dryness, needle track marks or bullous lesions, and note whether the skin is hot or cool to touch.
Several toxins may have a characteristic odor and will alert the provider to a possible diagnosis. Garlic odor in the breath of a patient with an unknown overdose may indicate thallium, organophosphate, arsenic, dimethyl-sulfoxide, selenium, or a phosphide ingestion; the odor of wintergreen is highly suspicious of a methylsalicylate ingestion; and, of course, the odor of distilled spirits may indicate an ethanol-containing beverage or substance. The odor of bitter almonds signifies the presence of cyanide; unfortunately only about 50% of people can detect this odor.
Differentiating Toxic versus Nontoxic Causes for Admission
It is important not to get anchored to the initial one or two aspects of the patient's presentation (anchoring bias). There are numerous medical conditions that can mimic an overdose and vice versa. When the history is unclear, unreliable, or simply unknown, one must consider medical or traumatic causes for the patient's altered state. Attempt to obtain collateral history from relatives, medics, or others who may know the patient or found him unresponsive. Computerized tomography of the head may be needed to rule out intracranial hemorrhage or mass lesions. Chest or abdominal radiographs should be considered based on the clinical scenario and physical findings. Laboratory tests to consider based on clinical presentation include thyroid stimulating hormone, blood cultures, arterial or venous blood gases, salicylate level, hepatic function tests, pregnancy test, lactate, and creatinine kinase (CK).
Laboratory tests important in the evaluation of the unknown overdose patient include basic metabolic panel, acetaminophen level, serum osmolality, hepatic function tests, and urinalysis. Monitoring organ function by periodically assessing liver and renal laboratory values, CK, and possibly serial electrocardiograms may allow early detection of the delayed toxidrome and assist in providing expeditious management. A pregnancy test is routinely obtained in the altered female of childbearing age.
One issue that has been a source of controversy is the utility of toxicology screening tests or the urine drug screens. Kellerman et al conducted a prospective study of 582 consecutive emergency department patients with suspected drug overdose and found that more than 95% of cases had no significant change in treatment or disposition in response to routine toxicologic screening1. Another test that is typically ordered indiscriminately is the salicylate concentration. In a retrospective case review of patients with salicylate concentrations obtained, and the presence of salicylates, Wood and colleagues concluded that “routine measurement of plasma salicylate concentrations is not required” unless there is a history of salicylate ingestion or the history and physical are unreliable and the patient has clinical features of salicylate poisoning2. Knowing the patient's past medical history and noting whether there are stigmata of a chronic disease process may prompt specific drug levels to be ordered. In patients with a history of seizure disorder who present with altered mental status, a postictal state or toxicity from anticonvulsive therapy should be considered. Similarly, a patient with a history or clinical evidence of congestive heart failure (CHF) or atrial fibrillation may have digitalis toxicity. Most hospital laboratories can perform serum levels of anticonvulsive medications (eg, phenytoin, phenobarbital, or carbamazepine) or digoxin. Although ethanol levels can be done in the hospital chemistry laboratory, other toxic alcohols typically require the toxicology laboratory to analyze sample send to a more sophisticated laboratories. This will take time and may not assist in management decisions. In such cases, hospitalists must rely on clinical presentation and application of supportive care. See Table 98-2 for tests to consider in ruling out other diagnoses that may be confused with ingestion and vice versa.
Table 98-2 Tests to Consider in the Unknown Poisoned Patient ||Download (.pdf)
Table 98-2 Tests to Consider in the Unknown Poisoned Patient
|Tests||Diagnoses to consider|
|Rapid glucose test||Hypoglycemia, hyperglycemia, DKA|
|BUN/Creatinine||Overdose leading to acute renal insufficiency|
|Complete blood cell count||Anemia, leukocytosis, leukopenia, blood dyscrasias|
|Acetaminophen||Acetaminophen overdose with potential hepatotoxicity|
|Serum osmolality||Toxic alcohol (ie, volatile) ingestion (calculate osmolal gap)|
|Urinalysis||Crystaluria (may indicate ethylene glycol ingestion)|
|Electrocardiogram||Cardiotoxic effects of cardiovascular or psychotropic drugs (QRS widening and QTc prolongation)|
|Computerized tomography||Intracranial process, (mass, hemorrhage, other)|
The options for decontamination have been systematically reviewed by several toxicology societies and expert consensus has been issued on each of the common techniques. Syrup of ipecac is essentially inefficient and ineffective in decontaminating the gut and is no longer recommended for acute or chronic ingestions presenting to the emergency department. Circumstances in which ipecac may be of benefit are indeed rare. If considered, its use should be discussed with the local poison center or medical toxicologist.
Activated charcoal has limited use for ingestions and is only recommended when the patient presents within one hour after taking a potentially toxic overdose, the airway is intact and protected, and the product can be adsorbed by activated charcoal. Remember, caustics, alcohols, and metals have very little to no adsorption by activated charcoal. Routine administration of activated charcoal in managing oral overdoses has little to no significant impact on hospital length of stay or patient outcomes. Multiple doses of activated charcoal may impart some benefit for significant or life-threatening ingestions of carbamazepine, theophylline, phenobarbital, dapsone, and quinine. Volunteer studies have shown increase elimination of amitriptyline, digoxin, phenytoin, salicylates, and sotalol; however, there is insufficient research to support a recommendation for use of multidose activated charcoal in these overdoses.
Gastric lavage is indicated when the patient has ingested a potentially lethal amount of a drug and presents within one hour of the ingestion. This procedure carries high morbidity and should not be performed in any patient with an unprotected airway, those who have ingested caustics or hydrocarbons (which may render the gut vulnerable to perforation), or those who are at risk of perforation due to an underlying medical or surgical condition. Intuitively, removing the pills or substance from the stomach affords less material to be absorbed. However, clinical and experimental trials have failed to support a significant benefit. When weighing the advantages and potential complications, this procedure is seldom done. The overall benefit of gastric lavage is questionable at best and generally does not offer any more advantage over activated charcoal .
In some cases, efforts to increase elimination are used. This typically involves the use of whole bowel irrigation (WBI), hemodialysis, or pH manipulation. Although theoretically, WBI seems an ideal option for certain ingestions, a critical review of the scientific literature revealed insufficient evidence to support or exclude its use for potentially toxic ingestions of drug packets, iron, zinc, or lead. WBI involves using a polyethylene glycol-electrolyte solution (eg, GoLytely [r]) as a volume cathartic administering this solution at a rate of 1500-2000 mL per hour via orgogastric or nasogastric tube. Volunteer studies seem to show some benefit when this is used to manage significant ingestions involving enteric-coated or sustained-release products. Patients with renal insufficiency from drug overdose, or who have evidence of ingesting a toxic alcohol (ethylene glycol, methanol-containing products) may be candidates for hemodialysis to increase clearance and correct metabolic disturbances. Significant ingestions of salicylates, lithium, theophylline, long-acting barbiturates, and carbamazepine may also be treated with hemodialysis.
Triage Considerations for Patients with Unknown Drug Ingestions
ICU versus Monitored General Bed
It is not uncommon for an overdosed patient to be mistriaged or admitted to an inappropriate level of care. In the majority of cases, the patient will have signs and symptoms that predict potential deterioration. Hospitalists must pay close attention to mental status, hemodynamics, and any ancillary test results obtained in the ED. Table 98-3 offers some broad guidelines in regard to admitting the overdose patient to an intensive care versus monitored bed. Consultation with the medical toxicologist or poison control center can help in making this decision. Of course, when in doubt, one must err on the side of the patient by placing him or her at the higher level of care until an adequate period of observation can be achieved.
Table 98-3 Triage Algorithm to ICU of Patients with Unknown Drug Overdose ||Download (.pdf)
Table 98-3 Triage Algorithm to ICU of Patients with Unknown Drug Overdose
- Does this patient have hemodynamic instability? Yes
- Non sinus cardiac rhythm
- Malignant hyperthermia (neuroleptic malignant syndrome)
- Does this patient have evidence of end-organ damage? Yes
- Unable to respond to verbal stimuli, GCS < 13, unable to protect airway
- Confusion requiring monitoring for respiratory depression, withdrawal states
- Renal failure or possibly requiring emergency dialysis for removal of toxin(s) or metabolites
- Hypertensive emergency
- Respiratory failure
- Heart block other than 1st degree AV block, QTc > 500 ms, Osborn wave
- Life-threatening electrolyte disturbances or hypoglycemia that requires ongoing frequent monitoring and treatment
- Disseminated intravascular coagulation (DIC)
- Seizures or other neurologic conditions requiring ICU care
- Impending multisystem failure
- Are there nursing requirements or other issues requiring ICU care? Yes
- 1:1 ICU nursing required to monitor and administer therapy
- Higher level of care due to limited resources on general medical floor
- Clinical judgment that higher level of care required? Yes
While the patient is on the ward, he or she may exhibit delayed toxic effects of the ingestion. Hospitalists must be aware of danger signs and symptoms occurring late that will need immediate attention. Do not overlook the possibility of acetaminophen toxicity, ingestion of illicit drugs, and withdrawal syndromes. Acetaminophen ingestion may present fairly benignly initially and turn acutely worse after 24 hours postingestion due to the production of a toxic metabolite. At this point, the antidote, N-acetylcysteine, is less effective and the patient will sustain added morbidity and possibly die from hepatic failure. Thus, it is extremely important to detect acetaminophen poisoning early rather than late.
In addition to acetaminophen, there are several agents that could lead to a delayed toxic syndrome if a significant overdose has occurred. These include oral hypoglycemics (sulfonylureas), insulin, tricyclic antidepressants, iron, thyroid hormone, and toxic mushrooms. Another example might be methanol, ethylene glycol, isopropyl alcohol. Symptoms from these products may not appear for more than six hours post ingestion, and in the case of thyroid hormone overdose, several days after the ingestion. While the patient is on the ward or intensive care unit, he must be reassessed for any changes in mental status and vital signs.
Additionally, patients may have ingested packets of a drug (usually illicit) that rupture and lead to significant toxicity and death. This could be the case for the patient presenting above, in which the history is unknown and the clinician must rely upon physical findings and rational use of the laboratory and antidotes.
Another concern for the admitted patient is the development of withdrawal syndrome. Benzodiazepine and alcohol withdrawal can lead to seizures. Therefore, the patient with unknown history and altered mental status should be carefully monitored for signs and symptoms of drug withdrawal. Patients who are admitted with abnormal vital signs and altered mentation must be carefully monitored for deterioration. Agitated patients may subsequently develop elevation in creatinine kinase (CK) and if poorly monitored, may be at risk for acute renal failure, self-injury, or injury to staff. Hospitalists need to be very careful about prescribing medications to control agitation that might interact with substances ingested or delay clearance.
The ability to protect the airway of patients with severe central nervous system depression must be assessed. It is in the patient's best interest to place him/her at a higher level of care early in the course of inpatient management, rather than later.
Further Decontamination and Supportive Care of the Overdose Patient
It is important to assess the need for further decontamination management. Although the majority of patients are stabilized in the emergency department prior to arriving on the ward, some may need continued decontamination. Continued gastric lavage may be needed if this was initiated in the ED. Patients who have had whole bowel irrigation initiated for appropriate reasons may need to have this continued until the effluent is clear. Likewise, if an infusion of an antidote (eg, naloxone, sodium bicarbonate, deferoxamine, insulin, pressors) was started prior to arrival to the ward, the effect will need to be assessed and reassessed during the initial management phase, particularly if the duration of action of the antidote may be shorter than the duration of action of the toxin (eg, naloxone treatment for methadone overdose). In the intentional overdose patient, flumazenil is not typically recommended due to risk of seizures from acute benzodiazepine withdrawal or coingestion of a proconvulsive drug. Table 98-4 describes common antidotes and their uses. In cases of impaired renal function, the on-call nephrologist must be notified early in event of further deterioration and a need for hemodialysis.
Table 98-4 Common Antidotes ||Download (.pdf)
Table 98-4 Common Antidotes
|N-Acetylcysteine||Acetaminophen, carbon tetrachloride|
|Hydrofluoric acid (rust removers and glass etching)||Calcium gluconate|
|Cyclic antidepressant - sodium channel antagonists||Sodium bicarbonate|
|Lead, arsenic, mercury||Dimercapto-succinic acid (Succimer)|
|Ethylene glycol, methanol||Ethanol, 4- methypyrizole (fomepizole)|
|Digoxin, cardiac glycosides||Digoxin-specific Fab|
|Cyanide||Cyanide antidote kit (sodium nitrite, sodium thiosulfate), hydroxocobalamin|
|Beta adrenergic antagonist||Glucagon, high-dose insulin/euglycemia|
|Calcium channel antagonist||Calcium chloride, high-dose insulin/euglycemia|
Consulting the Poison Control Center and Medical Toxicologist
Occasionally the provider's existing toxicology knowledge and the above provided information will not be enough to take the necessary steps. Knowing when and how to solicit the proper help is important. Texts, journals, and online sources can be very helpful, but gaining appropriate information to apply clinically can be time intensive and sometimes fruitless. There are ways to obtain easy access to poison specialists, no matter your location and the time of day, as long as you have access to a telephone. The United States poison center system, or poison control center system, includes 60 poison centers. By dialing 1-800-222-1222, anyone can gain access to the local poison center and speak with toxicology-trained poison specialists. Poison centers serve multiple functions for the medical community. They provide education and educational resources, and reduce the number of unnecessary hospital visits after poison exposures. More than 70% of the calls are managed at the site of the exposure and required no further medical attention. Most of the other 30% of the calls are from health care facilities.
The specialists in poison information are trained in poisoning management and triage, and this group includes physicians, pharmacists, nurses, and other poison information providers. Through a combination of local management protocols, specific online and text resources, and quick access to medical toxicologists, the poison information specialists provide the necessary advice to guide the management of the patient at hand. Medical toxicologists provide support for the providers answering the calls, and are on call in case the need for further expertise arises. When calling the poison center, specific information needed includes the patient's age, weight, substance to which the patient was exposed, time of exposure, up-to-date clinical picture including vital signs, laboratory studies, and ECG results if applicable, treatments administered thus far, and any particular questions you may have regarding management. With that information they can quickly provide advice about management, or if necessary, solicit the help of the medical toxicologist.
When Do You Need Involvement of a Medical Toxicologist?
Often the toxicologist is involved in discussions of complicated or controversial management, or if the caller has questions that are beyond the scope of practice of the poison specialist fielding the call. Of note, since each poison center has toxicologists on call, callers can request to speak directly with that physician. This can be particularly useful in cases in which direct and immediate feedback is crucial for complex medical cases that involve poisons and toxins. Some cases may require multiple conversations between the hospital provider and the toxicologist due to changes in management based on a dynamic clinical course and/or updated results of testing. In cases in which patients are in any sort of extremis due to poisoning, early involvement of a medical toxicologist is recommended.
Another important role of the poison center, the poison center specialist, and the medical toxicologist is to help assess the patient's stability and appropriateness for various disposition options. The poison center information specialist and medical toxicologist can assist the hospitalist in determining the need for appropriate transfer depending on capabilites of the treating facility and nearby facilities. Using poison centers or hospital-based toxicologists can result in better management and disposition of poisoned patients resulting in more efficient use of the health care system and reduced morbidity for poisoned or overdosed patients (Table 98-5).
Table 98-5 Toxicology Resources for Hospitalists ||Download (.pdf)
Table 98-5 Toxicology Resources for Hospitalists
- Toxicology Resources for Hospitalists
- Poison Center Hotline: 1-800-222-1222
- Goldfrank's Toxicologic Emergencies (Flomenbaum N, et al (eds) 8th ed)
- Critical Care Toxicology: Diagnosis and Management of the Critically Poisoned Patient (Brent J, et al (eds))
- Poisonings and Drug Overdose (Olson K, et al (eds) 5th ed)
- Handbook of Poisonous and Injurious Plants (Nelson LS, et al (eds))
- Online Resources
During the night, the patient received an additional 6 milligrams of midazolam for agitation and experienced intermittent visual hallucinations. Approximately 24 hours after being admitted, he was awake and oriented to person, place, and time. His pupils remained dilated and he remained amnestic to the previous day's events. He admitted to being homeless, having a history of depression and noncompliance with his antidepressant medications. Prior to being found in the park, he had ingested an unknown amount of over-the-counter sleeping pills. The pills contained an anticholinergic agent that caused the patient's toxidrome. He was subsequently evaluated by psychiatry and transferred to an inpatient mental health ward.