Where Tox Meets Teamwork

Join Tiffany as she speaks with ER physician and Medical Toxicologist, board-certified in Addiction Medicine, Dr. Alexandra Amaducci, to discuss the management of a critically ill patient presenting with a massive diphenhydramine overdose.   This scenario highlights that our ED team includes many different professions. In the next segment, Brett sits down with ED Pharmacist Jess Pescatore to discuss the role of ED pharmacists and how we can best work together in our day-to-day lives.

 

Diphenhydramine Overdose

Tiffany Proffitt, DO, and Alexandra Amaducci, DO

 

Pearls:

• Diphenhydramine overdose causes multiple toxidromes including anticholinergic symptoms, seizures, and sodium channel blockade with wide-complex dysrhythmias
• Tachycardia is often the first symptom of overdose to appear and the last to resolve.
• Sodium bicarbonate is the first-line treatment for wide-complex tachycardia; lidocaine and hypertonic saline are adjuncts when bicarb fails.
• Urinary retention, persistent tachycardia, and altered mental status are red flags that require close observation and may predict decompensation.

 

Background:

• Diphenhydramine affects multiple receptor types within the body including muscarinic, serotonergic, dopaminergic and opioid.
• Overdose causes multiple toxidromes including anticholinergic symptoms, seizures, and sodium channel blockade with wide-complex dysrhythmias
• Overdoses are becoming more common due to social media trends and challenges.
• Overdose has a bimodal distribution with ages 0-5 years being common ages for exploratory accidental ingestions and ages 13-19 being most common for intentional ingestion.
• Substance ingestion related seizures are also bimodally distributed in these age ranges with 13-19 being most common followed by 0-5.

 

Presentation:

• Diphenhydramine overdose causes multiple toxidromes including:
• CNS depression
• Anticholinergic symptoms (urinary retention, hallucinations/altered mental status,flushed skin, mydriasis, anhydrosis, dry mucous membranes)
• Overflow incontinence can be mistaken for urinary function so ultrasound or bladder scan should be used to confirm bladder emptying.
• Consider regular straight catheterization or foley placement to mitigate urinary retention and associated agitation.
• Seizures
• Tachycardia
• This is often the first symptoms to appear and the last to leave.
• Cardiotoxicity
• Tachydysrhythmias can occur due to sodium channel blockade.
• Look for QRS widening, QT prolongation and a terminal R wave in aVR as signs of possible sodium channel blockade.

 

Workup:

• Serial EKGs and continuous cardiac monitoring will be important.
• CBC and BMP should be obtained.
• LFT, VBG can also be considered depending on clinical context.
• Consider CNS imaging for other causes of CNS depression or seizure. 
• Evaluation for co-ingestion can be pursued as many products containing diphenhydramine also contain other medications.
• Consult your friendly toxicologist early to help guide management.

 

Treatment:

• Sodium Bicarbonate:
• Wide QRS or unstable rhythms should be treated with sodium bicarbonate.
• Start with 3 amps of sodium bicarb back to back to back.
• Follow with infusion: 3 amps in 1L D5W (not NS), run at 150–200 mL/hr.
• Goal: serum sodium 145–155 mEq/L; pH 7.45–7.55.
• Add 20–40 mEq K+ to infusion to maintain serum K >4.0.
• Hydrogen /potassium anti border in the cells requires a serum potassium in the normal range to function.
• Without and normal potassium levels the cells will hold onto potassium and excrete hydrogen ions thereby lowering the pH
• Lidocaine:
• Class IB antiarrhythmic that rapidly binds/unbinds sodium channels.
• Can resolve the sodium channel blockade and resolve QRS widening to stabilize rhythm.
• Initial loading dose of 1.5 mg/kg IV push.
• Can repeat loading dose once at 05.-0.75 mg/kg if refractory ventricular dysrhythmia
• Follow with an infusion of 1-4 mg/minute if needed.
• Hypertonic Saline:
• 100mL boluses can be repeated as needed until QRS narrows or seizure activity stops.
• Benzodiazepenes and propofol:
• Seizure activity can be treated with usual therapies like benzodiazepines.
• If intubation is needed, consider using propofol for sedation as it can help with seizure activity.
• Parasympathomimetics:
• These can temporarily reverse anticholinergic delirium.
• May help you get some more history from an altered patient.
• Physostigmine - often used on board questions, not often used in real practice.
• Dose: 0.5-1mg IV over 2-5 minutes.
• Bradycardia or seizure is possible and this medication should be avoided in patients with asthma or cardiac disease.
• Having atropine and lorazepam at the bedside is advisable.
• Rivastimine Patch
• Apply the patch in the mid upper back so it is more difficult for patient to remove.
• Comes in doses of 4.6, 9.5 or 13.3 mg/24hr, consider higher doses for more severe symptoms.

Disposition and Observation

• Admit all patients with moderate-to-severe symptoms.
• Monitor until asymptomatic with normal vitals, ECG, and mental status.
• Delay psych clearance until full resolution of toxicity.
• Diphenhydramine is not dialyzable due to high volume of distribution.

Summary:

• Treat diphenhydramine overdose as a tox emergency with high risk for seizures and cardiotoxicity.
• Prioritize early monitoring, bicarb, and airway management.
• Consider lidocaine and hypertonic saline when QRS remains prolonged.
• Physostigmine or rivastigmine may be used judiciously for agitation or delirium.
• Persistent tachycardia or changes in mental status should raise concern for progression and warrant ongoing observation.

 

 

References:

1. Finkelstein Y, Hutson JR, Freedman SB, Wax P, Brent J; Toxicology Investigators Consortium (ToxIC) Case Registry. Drug-induced seizures in children and adolescents presenting for emergency care: current and emerging trends. Clin Toxicol (Phila). 2013 Sep-Oct;51(8):761-6. PMID: 23957582.
2. Gilbert BW, Santiago RD, Huffman JB, Yoder NM, Hunninghake JC. Transdermal rivastigmine as a therapeutic option in severe diphenhydramine-induced anticholinergic toxicity: A case report and literature review. Pharmacotherapy. 2025 Jul;45(7):462-467. PMID: 40492363.
3. Carroll S, McGee M, Audette M, Tuttle M, Corcoran J, Stanton M, Feldman R. Lidocaine for diphenhydramine-induced ventricular tachycardia: A case report. Am J Emerg Med. 2026 Jan 21;102:131-134. PMID: 41610479.

 

The ED Pharmacist

Brett Murray, MD and Jessica Pescatore, PharmD

 

Pearls:

• ED pharmacists are pharmacotherapy experts embedded in the ED, optimizing drug choice, dosing, safety, and speed—especially when care is verbal, time-sensitive, and high-risk.
• A core ED pharmacy skill is anticipation: understanding ED workflow well enough to think 3–4 steps ahead. With their help, medications, dosing adjustments, and equipment are ready before the team asks for them.
• The strongest ED pharmacy programs are fully integrated and visible  - physically in the ED & part of the team.
• Physician/APP advocacy is often essential because many pharmacist “saves” are near-misses that never become obvious outcomes.

 

What Is an ED Pharmacist?

• Dedicated primarily to ED patients and physically present in the department (not just verifying orders remotely).
• Serves as the ED’s pharmacotherapy expert across a broad medication set used in vulnerable, fast-paced, high-stakes situations.
• Focuses on delivering medication therapy safely, efficiently, and accurately under time pressure.

The “Anticipation” Mindset

• A critical role they play is proactively anticipating what the patient/team will need next, rather than reacting after problems arise.
• Their training approach emphasizes being at the bedside even when medications are not immediately needed, to learn:
• ED evaluation and diagnostic workflows.
• Common sequencing of interventions and procedures.
• How care evolves in real time.
• Goal: be prepared so when the care team asks, medications/dosing plans are already thought through or ready to go.

Direct Patient Care Contributions

• Acts as an “external brain” for drug therapy—especially when normal medication safeguards are bypassed (verbal orders, rapid bedside decisions).
• Key value areas in real-time care:
• Drug selection and patient-specific dosing (renal function, comorbidities, weight-based dosing, etc.)
• Identifying drug–drug interactions and other hidden safety issues
• Reducing cognitive load for physicians/APPs/nursing by owning pharmacotherapy decisions, while others focus on diagnostics/procedures/operations.
• Hands-on operational help during resuscitation:
• Rapid procurement and preparation of time-critical meds (e.g., pressors, sedation).
• Priming lines, setting up smart pumps, helping speed time-to-therapy. 

Evidence for Impact

• Multiple studies over recent decades—especially more recent publications—support the integration of ED pharmacists into the care team.
• Reported benefits include:
• Reduced medication errors and interception of near-misses
• Improved outcomes tied to metrics EDs are judged on, including:
• Decreased time to antibiotics in sepsis (emphasis on appropriate antibiotics).
• Reduced door-to-needle time and door-to-cath-lab time.
• Reduced time to anticoagulant reversal.

Antimicrobial Stewardship in the ED

• Supports narrow/appropriate therapy using their knowledge of local antibiograms and resistance patterns.
• Helps evaluate prior cultures/hospitalizations for patients with frequent healthcare exposure.
• Culture callback programs:
• Reviewing culture/sensitivity results after discharge.
• Ensuring the outpatient antibiotic remains appropriate and adjusting therapy when needed.
• Potential downstream benefits discussed: fewer revisits/readmissions.

Toxicology and Poisoning Emergencies

• ED pharmacists are uniquely positioned for toxicologic care:
• Building a thorough exposure/med history to identify atypical presentation.
• Identifying potential toxidromes/causative agents at bedside.
• Recommending management and monitoring.
• Procuring and advising on antidotes.
• Liaising with poison centers and inpatient toxicology services.
• Operational pharmacy tasks included:
• Concentrated vasopressors/dextrose to limit volume.
• Building a workable insulin infusion approach when no protocol existed.
• Communicating with pharmacy/hospital leadership to enable urgent workflow changes.
• Post-case systems improvement:
• Need for protocols, electronic order sets, and “one-click” ordering to standardize rare, high-risk care.

Education and Training Pathways for ED Pharmacists

• PharmD is foundational; many pursue postgraduate residency training:
• PGY1: broad clinician training across hospital areas, often with ED exposure if available.
• PGY2: specialized emergency medicine pharmacy training.
• Additional training/certifications:
• ACLS instructor roles
• AHLS (hazardous life support)
• Master’s degrees (e.g., simulation)
• Informatics or quality-focused training
• Newer professional developments:
• Board certification exam specific to emergency medicine pharmacy practice.
• Growth of professional organizations specific to ED pharmacists.
• Early support from physician organizations via position statements - ACEP/ACMT 

How Physicians/APPs Can Support ED Pharmacists

• Promote full integration into ED care (not “satellite verification only”).
• Be champions and advocates—especially because many pharmacist interventions are prevention/near-miss interceptions that are hard to quantify.
• Support practice models that allow pharmacists to work at the top of their license:
• Collaborative practice agreements.
• Education, scholarly activity, and protocol/order set development.
• Practical, day-to-day support:
• Ensure pharmacists have a physical workspace in/near the ED team area to stay plugged into workflow and cues.
• Include them as part of the team culture and communication (recognizing the ED “in the mix” environment).

Common Friction Points and Realities

• Drug shortages:
• Restrictions/criteria may exist to preserve supply; if it’s truly unavailable, it’s usually gone.
• Pharmacists can proactively identify alternatives and communicate shortage strategies.
• Using the EHR/order entry as an “alert system”:
• Sometimes learners place questionable orders expecting pharmacy to instantly fix them.
• Instead, encourage providers to learn the correct ordering pathways—important for settings without 24/7 pharmacy coverage.
• High-acuity resuscitation tempo:
• Multiple rapid verbal requests can create competing priorities.  Understand that medication preparation/administration has real logistics and sequencing.
• Team benefits: trusting the process while the pharmacist executes a plan safely and quickly.

References:

1.  Patanwala AE, Warholak TL, Sanders AB, Erstad BL. A prospective observational study of medication errors in a tertiary care emergency department. Ann Emerg Med 2010;55:522–6.  PMID: 20074833
2. Stasiak P, Afilalo M, Castelino T, et al. Detection and correction of prescription errors by an emergency department pharmacy service. CJEM 2014;16:193–206.  PMID: 24852582
3. Patanwala AE, Sanders AB, Thomas MC, et al. A prospective, multicenter study of pharmacist activities resulting in medication error interception in the emergency department. Ann Emerg Med 2012;59:369–73. PMID: 22226174
4. Rothschild JM, Churchill W, Erickson A, et al. Medication errors recovered by emergency department pharmacists. Ann Emerg Med 2010;55:513–21. PMID: 20005011
5. BrownJN, BarnesCL, Beasley B, Cisneros R, Pound M, Herring C. Effect of pharmacists on medication errors in an emergency department. Am J Health Syst Pharm 2008; 65:330–3.  PMID: 18238771
6. Patanwala AE, Hays DP, Sanders AB, Erstad BL. Severity and probability of harm of medication errors intercepted by an emergency department pharmacist. Int J Pharm Pract 2011;19:358–62.  PMID: 21899616
7. Bond CA, RaehlCL. Clinical pharmacy services, pharmacy staffing, and hospital mortality rates. Pharmacotherapy 2007;27:481–93.  PMID: 17381374
8. McLaren R, Bond CA, Martin SJ, Fike D. Clinical and economic outcomes of involving pharmacists in the direct care of critically ill patients with infections. Crit Care Med 2008;36:3184–9.  PMID: 18936700
9. Anderegg SV, Wilkinson ST, Couldry RJ, Grauer DW, Howser E. Effects of a hospital wide pharmacy practice model change on readmission and return to emergency department rates. Am J Health Syst Pharm 2014;71:1469–79. PMID: 25147171
10. Leape LL, Cullen DJ, Clapp MD, et al. Pharmacist participation on physician rounds and adverse drug events in the intensive care unit. JAMA 1999;282:267–70. PMID: 10422996