Approach to the Undifferentiated Overdose
“…it is important to realize that these described toxidromes are dependent on a single offending agent. In reality, the clinical picture is often confounded by a polypharmacy overdose…”
Case
A 15-year-old female with a history of depression and ADHD who presents to the ED after an intentional overdose. Family notes that the patient is prescribed Prozac and Adderall, but they also found Benadryl and Ibuprofen in her room. On arrival, the patient was hypertensive to 140/82 and tachycardic to 118 bpm. Her other vital signs were within normal limits. The patient was alert and oriented to person, place, and time, but the father noted that she “seemed off” and was responding slowly to questions.
Overdoses are unfortunately increasing in the United States, with over 107,000 deaths occurring in 2021 alone. The majority of these were opioid related, but deaths secondary to stimulant use have also increased. It is important for physicians to have a framework on how to approach these cases, particularly those when the substance is unknown and/or in the case of polypharmacy.
Initial Evaluation
With all critical cases, initial stabilization of the patient takes precedence over specific diagnosis. Immediate attention should be focused on airway, breathing and circulation assessments. The “ABCs” of toxicology can also be thought to include “DE”, standing for dextrose and EKG. Point of care glucose testing and electrocardiograms are two quick bedside tests that provide immediate diagnostic information. In respect to the EKG, it is particularly important to assess for QRS widening (typically caused by sodium channel blocking drugs such as tricyclic antidepressants) or QT prolongation (typically from antipsychotics). It is prudent in all intoxication cases to rapidly establish intravenous access and place the patient on continuous telemetry monitoring. It should be noted that while these patients may appear stable on initial examination, this can often be transient. Thus, frequent reassessments should occur.
Figure 1: Abnormal intervals within an EKG may raise suspicion for the specific ingested drug class. AMBOSS. https://www.amboss.com/us/knowledge/ecg
While obtaining a history is incredibly useful, it can often be unreliable in this patient population, particularly in cases of self-harm when the patient may not wish to disclose everything. Additionally, intoxication often hinders the patient’s ability to provide a reliable history. In one prospective study, only 30.9% of pediatric and adult patients provided a history concordant with their eventual drug screen. Due to these discrepancies, it is important for providers to obtain history from other sources, including family and paramedics. Pharmacy staff may also be helpful with obtaining a list of the patient’s currently prescribed medications. It is also vital to recognize that patient presentations can vary widely based on multiple factors. Not only are timing and the amount of drug ingested important, but responses can change secondary to interactions with a patient’s baseline medications, underlying kidney or liver disease that may affect metabolization, and other concurrent pathologies such as trauma or infection.
In this case, the patient’s primary survey was intact. She had a glucose level of 84 reported by EMS and an EKG demonstrating tachycardia with a QTc of 459. The patient endorsed self-harm but was not open about what she had consumed.
Physical Examination
Physical examinations in the undifferentiated overdosed patient are vital for the emergency medicine physician to narrow down the inciting poisoning etiology. Toxidromes indicating either physiological excitation or depression can help guide physicians on how to best approach treatment modalities (Figure 1). However, it is important to realize that these described toxidromes are dependent on a single offending agent. In reality, the clinical picture is often confounded by a polypharmacy overdose. Important physical examination findings include pupil size, mental status, bowel sounds, and bladder size. The presence of sweat is also an important exam finding and should be performed by checking a patient’s armpit, the so-called “Tox Handshake”. Lastly, exposure is important to identify wounds, injection site, or medications placed on the skin such as fentanyl patches or insulin pumps.
In this case, neurological examination was notable for slight clonus and hyperreflexia. As stated earlier, the patient was alert and oriented to person, place, and time, but the father noted that she “seemed off” and was responding slowly to questioning. No dysmetria or ataxia were noted. Pupils were equal and reactive, without displaying mydriasis or miosis. The rest of the physical examination was largely unremarkable. While tachycardic, cardiac examination did not note murmurs, rubs or gallops. Auscultation of the lungs did not elicit wheezes or rales. The patient did endorse some generalized abdominal cramping, but her abdomen was soft and non-tender on palpation.
Figure 2: Toxidrome Physical Examination Findings. LearnPICU. Standford Pediatric Critical Care. http://www.learnpicu.com/toxidromes
Diagnostic Testing
Drugs of Abuse screens are typically sent in overdoses and can detect many common intoxicants such as cocaine metabolites, opiates, and benzodiazepines. However, thsee tests should be interpreted with caution, as a positive screen does not necessarily correlate with current intoxication. Acetaminophen and salicylate levels should be sent in all of these patients. Early recognition and treatment of acteaminophin and/or salicylate toxicity with n-acetylcysteine and sodium bicarbonate respectively is effective. Additionally, these common medications often do not show immediate symptoms, even if a lethal dose was taken. Ethanol levels are also a useful measurement, as they are quantitative and subsequently can give insight into a patient’s altered mental status.
In all suspected overdose patients, there are a additional lab values that are important to obtain, as they may change further management and aid with diagnosis. These include electrolyte measurements including magnesium and calcium, an assessment of kidney function through Cr/BUN, liver function tests, and an assessment of serum ketones. In patients with suspected respiratory, acid/base or cardiovascular pathologies, a blood gas and lactate can also be useful. The assessment of an osmolar gap may also be useful in certain cases, as elevated levels should raise suspicion for alcohol compounds other than ethanol, such as methanol.
In this case, our 15-year-old patient’s drug screen, acetaminophen, salicylate, and ethanol levels were all unremarkable. Further lab work was notable for a slight hypokalemia of 3.3 and a decreased bicarbonate level of 20.
Treatment
In cases where the offending agent is known, specific antidotes may be utilized. It is recommended to involve Poison Control (800-222-1222) early on after vital sign stabilization to help coordinate care in these instances. GI decontamination techniques such as activated charcoal can also be considered in patients depending on the timing since ingestion, the patient’s mental status, and the suspected agent.
The patient in our case appeared slightly altered and the timing of ingestion was presumed to be over 2 hours prior, so activated charcoal was not administered. The patient did have some features of serotonin syndrome, which could be explained by the patient’s Prozac prescription. These included her clonus, tachycardia (possibly confounded by her Adderall use) and hyperreflexia. As her mental status was reportedly worsening per her father’s, the patient was treated empirically with benzodiazepines and IV fluids. She was admitted to the Pediatric Intensive Care Unit (PICU) for further observation and management. Cyproheptadine, a serotonin receptor antagonist, was considered but not administered due to the relatively mild degree of the patient’s symptoms. She did not have any seizures or require intubation while inpatient, two dreaded complications of serotonin syndrome. Her symptoms resolved over the following day with supportive care. She was subsequently evaluated by psychiatry for her suicidal ideation.
AUTHOR: Kyle Volpe, MD, is a fourth-year emergency medicine resident at Brown Emergency Medicine Residency
FACULTY REVIEWER: Meghan Beucher, MD, is an Assistant Proferssor of Pediatrics and Emergency Medicine at Brown University
References
1. Erickson TB, Thompson TM, Lu JJ. The approach to the patient with an unknown overdose. Emerg Med Clin North Am. 2007;25(2):249-vii. doi:10.1016/j.emc.2007.02.004
2. Monte AA, Heard KJ, Hoppe JA, Vasiliou V, Gonzalez FJ. The accuracy of self-reported drug ingestion histories in emergency department patients. J Clin Pharmacol. 2015;55(1):33-38. doi:10.1002/jcph.368
3. Mahr, Krista. “U.S. Drug Overdose Deaths Surpass 107,000 Last Year, Another Record.” POLITICO, 25 July 2022, www.politico.com/news/2022/05/11/drug-overdose-deaths-2021-record-00031709.
4. Olson KR, Pentel PR, Kelley MT. Physical assessment and differential diagnosis of the poisoned patient. Med Toxicol 1987; 2:52.