All posts by Erica Simon

EM@3AM – Acute Coronary Syndrome

Author: Erica Simon, DO, MHA (@E_M_Simon, EM Chief Resident, SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC, USAF)

Welcome to EM@3AM, an emdocs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

A 69 year-old male with a history of hypertension, hyperlipidemia, and smoking presents with pre-cordial chest pain radiating to his right upper extremity, associated with shortness of breath. The patient reports the onset of his symptoms one hour prior to arrival, while mowing his lawn. He characterizes his chest pain as an 8/10 “tightness” and notes nausea that “comes in waves.” ROS is negative for recent illness, travel, and hospitalization within the previous 90 days. The patient denies personal or familial history of DVT/PE.

 Triage VS: BP 157/98, HR 102, RR 22, T99.8°F Oral, SpO2 98% on room air

What diagnosis do you suspect? What’s the next step in your evaluation and treatment?

Answer: Acute Coronary Syndrome (ACS)1-4

  • ACS: Consists of unstable angina, NSTEMI, and STEMI
  • Risk Factors: Hypertension, diabetes, dyslipidemia, tobacco use, family history of CAD (i.e. – CAD in a male primary relative younger than 55 years of age, or CAD in a female primary relative younger than 65 years of age), HIV/AIDS, SLE, cocaine use.1 
  • Presentation: Chest pain or pressure radiating to the neck, jaw, or upper extremities; mid-epigastric pain, diaphoresis, nausea with or without emesis.2
    • Increased likelihood of acute MI:3
      • Chest pain with radiation to right arm or shoulder: positive likelihood ratio (+LR) 4.7; 95% CI 1.9-12
      • Chest pain with radiation to both arms or shoulders: +LR 4.1; 95% CI 2.5-6.5
      • Chest pain associated with exertion: +LR 2.4; 95% CI 1.5-3.8
  •  Evaluation:
    • Focused H&P, serial EKGs, cardiac biomarkers, chest radiograph
      • Troponin I most sensitive marker of cardiac myocyte damage (positive in NSTEMI and STEMI).1
  •  Treatment:1
    • Administer non-enteric coated, chewable ASA.
    • Antithrombotic therapy and/or anti-platelet therapy as appropriate per the diagnosis.
    • Nitrates to relieve chest discomfort (caution in the setting of inferior STEMI => perform R-sided EKG to rule out RV infarct,  a pre-load dependent condition).
    • Supplemental oxygen therapy for patients with shortness of breath, signs of acute heart failure, or cardiogenic shock.
  •  Pearls:
    • Females, diabetics, and the elderly often present atypically.
    • Keep in mind there are numerous ACS mimics: aortic dissection, PE, pneumonia, pericarditis, myocarditis, pleurisy, PUD, etc.
    • Previous non-invasive cardiac stress testing does not rule out coronary artery disease.4 


  1. Qazi M and Patel P. Acute Coronary Syndrome. In: Ferri’s Clinical Advisor 2017. Philadelphia: Saunders Elsevier, 2017: 25-29.e1.
  2. Kumar A and Cannon C. Acute Coronary Syndromes: Diagnosis and Management, Part I. Mayo Clin Proc. 2009; 84(10): 917-938.
  3. Swap C and Nagurney J. Value and limitations of chest pain history in the evaluation of patients with suspected acute coronary syndromes. JAMA. 2005; 294(20): 2623-2629.
  4. Walker J, Galuska M, Vega D. Coronary disease in emergency department chest pain patients with recent negative stress testing. West J Emerg Med. 2010; 11(4): 384-388.

For Additional Reading:

EKG Findings in ACS:

ST Elevation in aVR:

Risk Stratification:

Management of Low-Risk Chest Pain:

EM@3AM – Anticholinergic Toxicity

Author: Erica Simon, DO, MHA (@E_M_Simon, EM Chief Resident, SAUSHEC, USAF) and Daniel Sessions, MD (EM Associate Program Director, SAUSHEC, USAF / Medical Toxicologist, South Texas Poison Center) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC, USAF)

Welcome to EM@3AM, an emdocs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

A 62 year-old female, escorted by her son, presents to the emergency department for altered mental status. The son reports his mother as being in her usual state of health during a visit the night prior, but per the family maid, was severely confused upon awakening one hour prior to arrival.  A phone call to the patient’s daughter reveals a ROS positive only for a medication change: chlorpromazine prescribed for hiccups.

 Triage VS: BP 172/101, HR 127, RR 28, T103.2°F Oral, SpO2 98% on room air

Accucheck: 137

Upon initial evaluation the patient is oriented only to herself. Her pupils are 5mm bilaterally, she is flushed, her skin is dry, and her capillary refill is > 3 seconds. Her abdominal exam is remarkable for a palpable, distended bladder.

What do you suspect as a diagnosis? What’s the next step in your evaluation and treatment?

Answer: Anticholinergic Toxicity1-5

  • Precipitating Causes: Amantadine, antihistamines, antiparkinsonian medications, antipsychotics, cyclic antidepressants, dicyclomine, atropine, phenothiazines, scopolamine, Jimson weed.1 
  • Presentation: Classically “hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter, full as a flask, tachy as a pink flamingo.”
  • Evaluation:
    • Focused H&P:1
      • Perform a medication reconciliation
      • VS: obtain rectal temperature, look for tachycardia
      • Neurologic examination: possible altered mental status, mydriasis, visual deficits
      • Additional exam findings: patient commonly flushed with dry skin and a prolonged capillary refill.  Palpate the abdomen in search of a distended bladder.
  • Treatment:1
    • Delirium/Agitation: benzodiazepines
      • Avoid haldoperidol – may worsen symptoms
    • Urinary retention: foley placement
    • Hyperthermia: active cooling with misting/fanning, cooled IV fluids; benzodiazepines for shivering
    • Hypotension: IVF; if intractable, consider norepinephrine
    • EKG demonstrating conduction delays: sodium bicarbonate to overcome impaired sodium conduction
    • Although physostigmine has traditionally been recommended only for patients with life-threatening anticholinergic toxicity (given concern regarding its associated complications, i.e. – severe agitation, seizures, persistent hypertension, and hemodynamic compromise secondary to tachycardia),3 newer data report its relative safety and efficacy in reversing the anticholinergic toxidrome; specifically anticholinergic delirium.4,5 
  •  Pearls:
    • Consider anticholinergic toxicity in the differential diagnosis of an altered patient with residual urine > 200-300 mL.2
    • Exercise caution in the use of physostigmine if there is concern for TCA toxicity, arrhythmias, or QRS/QTc prolongation, as upon administration physostigmine displays a dose dependent AV nodal conduction delay.2
    • In 2013, the American Association of Poison Control Centers reported three deaths secondary to an anticholinergic drug (benztropine).3


  1. Thornton S and Ly B. Over-the Counter Medications. In: Emergency Medicine: Clinical Essentials. Philadelphia, Saunders Elsevier. 2013; 1334-1342.e1.
  2. Stilson M, Kelly K, Suchard J. Physostigmine as an antidote. Cal J Emerg Med. 2001. 2(4): 47-48.
  3. Mowry J, Spyker D, Cantilena L, McMillan N, Ford M. 2013 Annual report of the American Association of Poinson Control Centers’ National Poison Data System (NPDS): 31st annual report. Clin Toxicol. 2014; 52: 1032-1238.
  4. Watkins J, Schwarz E, Arroyo-Plasencia A, Mullins M; Toxicology Investigators Consortium Investigators. The use of physostigmine by toxicologists in anticholinergic toxicity. J Med Toxicol. 2015; 11(2):179-184.
  5. Dawson A and Buckley N. Pharmacological management of anticholinergic delirium – theory, evidence, and practice. Br J Clin Pharmacol. 2016; 81(3): 516-524.

 For Additional Reading:

Physostigmine for Anticholinergic Toxicity:

Physostigmine for Management of Anticholinergic Toxidrome

EM@3AM – Acute Cholecystitis

Author: Erica Simon, DO, MHA (@E_M_Simon, EM Chief Resident, SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC, USAF)

Welcome to EM@3AM, an emdocs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

A 41-year-old obese female presents for evaluation of severe right upper quadrant pain and nausea without emesis. The patient reports post-prandial pain of one months duration, acutely worsening prior to presentation following the consumption of a bacon cheeseburger. ROS is negative for sick contacts, foreign travel, and changes in bowel habits. The patient denies a surgical history.

Triage VS: T101.6°F Oral, HR 134, BP 147/99, RR 24, SpO2 98% on room air

What is the patient’s diagnosis? What’s the next step in your evaluation and treatment?

Answer: Acute Cholecystitis1-4

  • Risk Factors: oral contraceptives or estrogen replacement therapy (alters cholesterol and bile salt metabolism leading to gallstone formation and gallbladder hypomotility1), diseases of the terminal ileum (e.g. Crohns; secondary to poor bile salt reabsorption), cirrhosis (decreased bile acid secretion), hemolytic diseases (pigmented gallstones), pregnancy, obesity, TPN
  • Presentation: RUQ or epigastric pain, postprandial pain, nausea +/- emesis, +Murphy’s sign (+LR: 2.8; 95% CI, 0.8-8.62), +/- fever
  • Evaluation:
    • US (Sensitivity 95%, Specificity 98%3): sonographic Murphy’s, pericholecystic fluid, gallstones/biliary sludge, gallbladder wall thickening > 3mm.
    • CBC, LFTs
      • CBC: often demonstrates leukocytosis
      • LFTs: transaminitis; allows for evaluation of choledocolithiasis
  • Treatment:
    • Antimicrobials:
      • Mildly ill: ciprofloxacin 400 mg IV + metronidazole 500 mg IV
      • Critically ill: vancomycin 20 mg/kg (up to 2 g) IV + piperacillin/tazobactam 4.5 g IV
    • Fluid Resuscitation
    • Pain control
    • Anti-emetic PRN
    • Surgical Consultation – cholecystectomy
  • Pearls:
    • Diabetes is a risk factor for emphysematous cholecystitis:3 initiate antibiotic therapy directed against Gram-negative rods and anaerobes, and consult surgery.
    • Include acalculous cholecystitis in your differential diagnosis of the critically ill: RUQ pain, epigastric pain, and nausea are absent upon initial evaluation in up to 75% of these patients.1



  1. Welch J, Chike V, Bowens N, Arnell T, Ferri F. Acute Cholecystitis. First Consult. 2011. Elsevier, Philadelphia, PA.
  2. Trowbridge R, Rutkowski N, Shojania K. Does this patient have acute cholecystitis? JAMA. 2003; 289(1): 80-86.
  3. Glasgow R, Mulvihill S. Treatment of Gallstone Disease. In: Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. Philadelphia: Saunders Elsevier, 2016:1134-1151.e5.
  4. Senturk S, Miroglu T, Cilici A, Gumua H, Tekin R, et al. Diameters of the common bile duct in adults and postcholecystectomy patients: a study with 64-slice CT. Eur J Radiol. 2012; 81(1): 39-42.

EM@3AM – Acute Limb Ischemia

Author: Erica Simon, DO, MHA (@E_M_Simon, EM Chief Resident, SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC, USAF)

Welcome to EM@3AM, an emdocs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

A 62-year-old male with a history of paroxysmal a.fib (CHADS2: 0; daily ASA1) presents for evaluation of left lower extremity (LLE) numbness and weakness. The patient reports the onset of his symptoms five hours prior to arrival, during his granddaughter’s dance recital. He denies slurred speech, visual changes, facial and upper extremity sensory and motor deficit. He denies right lower extremity symptoms.  HPI is negative for back pain, recent trauma, joint pain, and joint redness prior to symptom onset. ROS is unremarkable. Surgical history is significant only for remote inguinal hernia repair.

 Triage VS: T99.7°F Oral, HR 82, BP 129/76, RR 24, SpO2 98% on room air

Physical exam:

Neuro: LLE: weakness of plantarflexion and dorsiflexion; decreased sensation L4-S2 dermatomes below the knee

Cardiac: irregularly irregular

Vascular: Cool, mottled LLE; femoral pulse palpable, popliteal pulse non-palpable, dorsalis pedis and posterior tibial pulses non-palpable. Doppler confirms the absence of popliteal, dorsalis pedis, and posterior tibial pulses.

EKG: NSR, 82 bmp, axis WNL, no ST-T wave changes, QT WNL

What is the patient’s diagnosis? What’s the next step in your evaluation and treatment?

Answer: Acute Limb Ischemia1-4

  • Risk Factors: Conditions that pre-dispose to thrombosis (hypercoagulable state, arterial aneurysms, peripheral arterial disease (atherosclerotic plaque rupture), etc.) or embolism (atrial fibrillation, post MI, left ventricular dysfunction, mechanical cardiac valve with sub therapeutic anticoagulation, etc.).
    • Trauma is an uncommon etiology: limb ischemia may occur secondary to direct vessel injury and subsequent thrombosis.2
  • Clinical Presentation: Classically taught as the six Ps: pain, paresthesia, pallor, poikilothermia, pulselessness, and paralysis. Patients may also report claudication.
    • Considered to be acute in onset if symptoms began within 2 weeks of presentation 2
  • Evaluation:
    • Assess limb: appearance, temperature, pulses (including by Doppler), sensation, and strength
    • Lower extremities: ABI < 0.3 = subcritical acute ischemia2
  • Treatment:
    • Consult vascular surgery:
      • The Society for Vascular Surgery publishes classification standards based upon clinical and Doppler findings (limb viable vs. threatened vs. irreversibly damaged) which direct management and treatment.4
    • Discuss initiation of heparin bolus 80 U/kg, then 18 U/kg/hr + ASA PO.2
  • Pearls:
    • Palpable pulses in the contralateral extremity suggests embolism as the underlying etiology.3
    • Morbidity and mortality rates are high in patients with acute limb ischemia: 10-15% undergo limb amputation during hospitalization.2



  1. Hart R, Pearce L, Rothbart R, McAnulty J, Asinger R, et al. Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke prevention in atrial fibrillation investigators. J Am Coll Cardiol. 35(1):183-187.
  2. Creager M, Kaufman H, Conte M. Clinical Practice. Acute limb ischemia. N Engl J Med. 2012; 366(23):2198-2206.
  3. Earnshaw J. Acute Ischemia: Evaluation and Decision Making. In: Rutherford’s Vascular Surgery. 8th ed. Philadelphia: Saunders Elsevier, 2014: 2518-2527.e1.
  4. Rutherford D, Baker J, Ernst C, Johnston K, Porter J, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg. 1997; 26(3): 517-538.

EM@3AM – Acute Angle Closure Glaucoma

Author: Erica Simon, DO, MHA (@E_M_Simon, EM Chief Resident, SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC, USAF)

Welcome to EM@3AM, an emdocs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

A 62 year-old female with a PMHx of hypertension presents for evaluation of severe left eye pain associated with blurred vision, headache, and nausea.  The patient reports the sudden onset of her symptoms as occurring 30 minutes prior to arrival while entering a movie theater. ROS is negative for sick contacts, ocular discharge, and foreign body sensation. The patient wears glasses that she is “unable to see without.”

Triage VS: HR 122, BP 132/91, RR 18, SpO2 98% RA
Corrected: OD 20/20, OS 20/200, OU 20/40

Ocular examination:
-No evidence of foreign body
-Fluorescein stain without uptake
-IOP 15 mmHg

-EOMI, pupil (5mm) mid-position and fixed, conjunctival injection, hazy cornea
-No evidence of foreign body
-Fluorescein stain without uptake
-IOP 34 mmHg

What is the patient’s diagnosis? What’s the next step in your evaluation and treatment?

Answer: Acute Angle Closure Glaucoma1-3

  • Risk Factors: hyperopia, age >60, female sex
  • Presentation: sudden onset, severe eye pain +/- blurred vision, +/- nausea or emesis, +/- headache, pupil mid-positioned +/- fixed or sluggish, IOP >20mmHg
  • Precipitating factors:
    • Transition to dim lighting
    • Medications
      • Anticholinergics (topicals: cyclopentolate, tropicamide, etc., or systemic: antihistamines, antipsychotics, anticonvulsants, anti-parkinsonian medications, atropine, etc.)
      • Adrenergic agents (vasoconstrictors, bronchodilators, appetite depressants, etc.)
    • Emotional stress/pain (mydriasis secondary to increased sympathetic tone)
  •  Treatment:
    • Consult ophthalmology
    • Decrease production of aqueous humor:
      • Beta blockade: timolol 0.5% gtt
      • Alpha-2 agonists: apraclonidine 1% gtt or brimonidine 0.2% gtt
      • Carbonic anhydrase inhibitors:
        • Acetazolamide gtt or dorzolamide 2% gtt + 500 mg PO or IV acetazolamide
    •   Improve outflow of aqueous humor:
      • Cholinergic agent: pilocarpine 2% gtt
    • Decrease volume of aqueous humor:
      • Osmotic diuretic: mannitol 1-2g/kg IV
  •  Pearls:  
    • Obtain a thorough medical history:
      • B-blockade: caution with heart blocks, history of severe bronchospasm
    • Carbonic anhydrase inhibitors: avoid in sickle cell patients
    • Pilocarpine therapy should not be initiated until one hour following the instillation of an aqueous humor reducing agent:
      • Pilocarpine constricts the ciliary muscle causing miosis and increasing the axial thickness of the lens. While this allows for increased outflow of aqueous humor, it may also paradoxically worsen the condition by reducing the depth of the anterior chamber.2
    •  Suspect medication induced acute angle closure glaucoma if elevated IOP is present bilaterally.4


  1. Tintinalli J, Kelen G, Stapczynski J, Ma O, Cline D, et al. Tintinalli’s Emergency Medicine. 8th ed. New York: McGraw-Hill; 2016. Chapter 60, Aneurysmal Disease.
  2. Jovina S, Aquino M, Chew P. Angle-Closure Glaucoma. In Ophthalmology. 4th ed. Philadelphia, Elsevier 2014; 10.12: 1060-1069.e2.
  3. Day A, Nolan W, Malik A, Viswanathan A, Foster P. Pilocarpine induced acute angle closure. BMJ Case Rep. 2012; 2012.
  4. Aminlari A, East M, Wei W, Quillen D. Topiramate induced acute angle closure glaucoma. Open Ophthalmol J. 2008; 2:46-47.

EM@3AM – Acute Chest Syndrome

Author: Erica Simon, DO, MHA (@E_M_Simon, EM Chief Resident, SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC, USAF)

Welcome to EM@3AM, an emdocs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

 A 4-year old male with a history of sickle cell anemia presents to the ED for evaluation of fever of two days duration (Tmax 103.2) and progressively worsening shortness of breath. The patient’s parents report 48-hour hospitalization 6 months prior secondary to a vaso-occlusive crisis (pain localized to the extremities). ROS is negative for sick contacts. Medications include penicillin prophylaxis. Immunizations are up to date.

VS: HR 127, BP 97/64, RR 32, SpO2 91% on room air.

Physical examination:
Neuro: GCS 15
HEENT: PERRLA, TMs clear bilaterally, nasal mucosa unremarkable, oropharynx clear and moist, no lymphadenopathy
CV: Tachycardia, cap refill 2 secs
Pulm: End-expiratory wheezing
Abdomen: ND, NT, no guarding or rebound
GU: Without findings
Derm: No rashes

CXR demonstrates multi-lobar infiltrate.

What is the patient’s diagnosis? What’s the next step in your evaluation and treatment?

Answer: Acute Chest Syndrome (ACS)1-3

  • Presentation: fever (>38.5°C or 101.3°F), tachypnea, cough, +/-chest pain, +/- wheezing and new infiltrate on CXR
  • Evaluation:
    • CXR, CBC, reticulocyte count, VBG, blood cultures, sputum culture2
    • Consider underlying etiologies and evaluate as appropriate:
      • Sepsis
      • PNA
      • PE
      • Fat embolism
  •  Treatment:
    • Bronchodilators – improve peak expiratory flow2
    • Incentive spirometry and analgesia – prevent development/worsening of atelectasis
    • Empiric antibiotic therapy following procurement of culture samples (target Chlamydia, Mycoplasma, and Streptococcus)
    • Oxygen therapy to maintain SpO2 >92%
    • Fluid resuscitation targeting euvolemia (avoid iatrogenic pulmonary edema)
    • Exchange transfusion (in consultation with heme/onc) for:
      • Severe hypoxemia
      • Multi-lobar involvement
      • Worsening course
  •  Pearls:
    • Acute chest syndrome is the leading cause of death in sickle cell patients in the U.S. (12% mortality).2
    • Infection is most common cause of ACS ( C. Pneumoniae and RSV).
    • A normal pulmonary exam is most frequently associated with ACS.2
    • ACS rapidly progresses to ARDS = admit to ICU level care


  1. Tintinalli J, Kelen G, Stapczynski J, Ma O, Cline D, et al. Tintinalli’s Emergency Medicine. 8th ed. New York: McGraw-Hill; 2016. Chapter 236, Sickle Cell Disease and Hereditary Hemolytic Anemias.
  2. Vichinsky E, Neumayr L, Earles A, Williams R, Lennette E, et al. Causes and outcomes of the acute chest syndrome in sickle cell disease. N Engl J Med. 2000; 342:1855-1865.
  3. Traill L and Barton M. Focus On: Acute Chest Syndrome – The Critical Cough. American College of Emergency Physicians Clinical and Practice Management. 2008. Available from:—Practice-Management/Focus-On–Acute-Chest-Syndrome—The-Critical-Cough/

Influenza and Considerations Regarding Infectious Mimics

Author: Erica Simon, DO, MHA (@E_M_Simon, EM Chief Resident at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

A 57-year-old male with a previous medical history of hypertension and hyperlipidemia presents to the emergency department (ED) with the chief complaint of chills, headache, cough, and generalized malaise.  The patient reports the onset of his symptoms 48 hours prior with temperatures peaking at 102.2°F.  Review of systems is notable for a sick contact – a granddaughter with “the flu.”  The patient denies nausea, vomiting, diarrhea, and abdominal pain.  He denies recent travel and reports an inability to obtain an influenza vaccination secondary to a lack of health insurance.

Triage Vital Signs:  T103.1°F, HR 126, RR 18, SpO2 95% RA

When approaching this patient, what life threatening conditions that you should be considering?  While a diagnosis of influenza is likely high on your list, what clues should you be looking for during the physical examination that might suggest the need for an alternative evaluation and treatment?

Let’s take a minute to review influenza mimics.

Epidemiology of Influenza

In the US, fever, headache, and cough are among the top ten most cited reasons for patients to seek emergency care.1  From 2007-2009, nearly 1 million individuals presenting with the aforementioned symptoms were diagnosed with influenza by an EM physician.2  Complications secondary to influenza result in the annual hospitalization of 220,000 persons,3 representing estimated healthcare costs of  $4.6 billion.4  Today influenza demonstrates a mortality rate of 1.4 deaths per 100,000 laboratory-confirmed cases.4

A Review of Influenza

Influenza Pathophysiology

Influenza A, B, and C, named according to their respective surface proteins, are single-stranded RNA viruses capable of human infectivity.5-7  Influenza B and C are responsible for the majority of human infections and are transmitted through aerosolized viral particles.6,7  Influenza A infection (commonly affecting birds, horses, swine, and dogs) may occur through direct contact with an infected animal, exposure to a contaminated environment, or the ingestion of inadequately prepared food stuffs.

Upon failure of host immunological defenses (IgA secretory antibody and mechanical respiratory mucociliary clearance), influenza viruses invade columnar respiratory epithelium, lymphocytes, polymorphoneuclear leukocytes, and monocytes, resulting in the release of pro-inflammatory cytokines, ultimately affecting a number of organ systems and resulting in variable manifestations of illness.4-8

Organ System  Organ System Effects of Influenza
Respiratory System most commonly affected: destruction of respiratory epithelium results in edema of the tracheobronchial tree.8,9
Neurologic Influenza virus may directly damage the thalamus, tegmentum, or cerebellum resulting in encephalopathy, seizures, or coma.  Viral-associated apoptosis has also been associated with myelitis, Guillain-Barre syndrome, and encephalitis.  Reye syndrome may occur in the setting of aspirin administration.8,10
Cardiovascular Pericarditis and myocarditis infrequently occur secondary to influenza A and B infections.8,11
Gastrointestinal Hematogeneous spread of infected lymphocytes may result in emesis and diarrhea.12
Hematologic Leukocytosis is a common cell-mediated immune response to influenza infection.13
Musculoskeletal Myositis and myoglobinuria are frequently observed in the pediatric population and are associated with elevated CK levels.8,14

Presenting Signs and Symptoms

Malaise, lethargy, and altered mental status may occur at the extremes of age.15   Pediatric patients commonly report nausea, emesis, and abdominal pain, while adults and adolescents detail symptoms including: fever, headache, myalgias, malaise, anorexia, rhinorrhea, pharyngitis, cough, and chest discomfort.4,7,8,15

Diagnosing Influenza

Although influenza symptoms may be caused by a number of respiratory viruses (RSV, parainfluenza virus, adenovirus, rhinovirus, and coronavirus), in the setting of a local outbreak, current studies identify a provider accuracy of 80-90% in the clinical diagnosis of influenza infection.16-18  Today the Centers for Disease Control and Prevention (CDC) recommends formal diagnostic testing for all patients at high risk of complications secondary to influenza (Table 2).19

Table 2. Populations at Risk for Influenza Complications19
–       Children ³ 6 months of age to 4 years (59 months)

–       Adults ³ 50 years of age

–       Individuals with chronic pulmonary, cardiovascular, renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus)

–       Individuals who are immunosuppressed

–       Women who are or will be pregnant during influenza season and up to two weeks postpartum

–       People ages 6 months – 18 years receiving long-term aspirin therapy and might be at risk for Reye syndrome after influenza infection

–       Residents of nursing homes or long-term care facilities

–       American Indians/Alaska Natives

–       The super obese (body mass index >40)

–       Health care personnel

–       Caregivers of children <5 years and adults ³ 50 years of age

Numerous mechanisms may be utilized for the identification of influenza infection including: rapid antigen detection tests, direct immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), viral culture, and serology.20,21  Rapid antigen detection tests offer the greatest utility in the emergency setting, as average sample processing time is 15 minutes (reported sensitivity 50-70%, specificity > 90%); however, positive and negative predictive values must be interpreted with respect to the local prevalence of influenza infection and patient presentation.20  False negatives are likely to occur in the midst of the influenza season, when prevalence is high.  If a diagnosis is likely to alter clinical decision-making, the CDC recommends confirmation of a negative rapid antigen test with RT-PCR.21

Treatment and Chemoprophylaxis

In the majority of cases, influenza infection is self-resolving and does not require treatment.7  In populations at risk for complications secondary to infection (Table 1), presenting within 48 hours of the onset of symptoms, the CDC recommends treatment with neuraminidase inhibitors according to Table 3 below.  Neuraminidase inhibitors prevent viral aggregation and the release of infectious nucleic acids to nearby host cells, therefore limiting infection.21  Double-blinded, placebo-controlled studies of influenza antiviral agents demonstrated an average reduction in febrile influenza illness of 1-1.6 days as compared to placebo when neuraminidase inhibitor therapy was initiated within 48 hours of symptom onset.23-25  This should be weighed against the risk of GI side effects.

Individuals for whom chemoprophylaxis should be considered include unvaccinated family and close contacts of persons with suspected or confirmed cases of influenza at high risk for complications secondary infection.26  In randomized, placebo-controlled trials, oseltamivir and zanamivir were efficacious in the prevention of influenza among persons administered chemoprophylaxis after exposure to a household member of close contact with laboratory confirmed influenza (oseltamivir 68-89%, zanamivir 72-82%).27,28  See Table 3 for chemoprophylaxis recommendations.

Table 3. Influenza Treatment and Chemoprophylaxis Recommendations29

Antiviral Delivery Method Recommendations for Use Not Recommended for Use Adverse Effects
Oseltamivir (Tamiflu©) Per Os Treatment: age ≥ 14 days*  Chemoprophylaxis: age ≥ 3 months* N/A Nausea, emesis, rare cutaneous reactions, transient neuropsychiatric events.
Zanamivir (Relenza©) Inhalation Treatment: age ≥ 7 years  Chemoprophylaxis: age ≥ 5 years Persons with respiratory diseases.  Contraindicated in patient allergy to milk protein. Allergic reactions: oropharyngeal or facial edema.  Diarrhea, nausea, sinusitis, bronchitis, headache, and ENT infections.
Peramivir (Rapivab©) Intravenous Age ≥ 18 years N/A Diarrhea, rare cutaneous reactions, transient neuropsychiatric events.
*FDA-approved indication.  The use of oral oseltamivir in the treatment of influenza in infants <14 days, and chemoprophylaxis in infants 3 months to 1 year of age, is recommended by the CDC and American Academy of Pediatrics.

Influenza Mimics

Current studies indicate that up to 70% of patients presenting with influenza-like illnesses are not infected with the influenza virus.26  Table 4 addresses infectious clinical conditions that commonly present as an influenza-like illness, along with pearls and pitfalls.

Table 4. Infectious Mimics of Influenza

Infectious Etiologies
Patient Presentation Clinical Condition Pearl/Pitfall Treatment
Hemodynamic instability or altered mental status Sepsis30 -Suspected or identified infection in patients meeting two or more of the following Systemic Inflammatory Response Syndrome (SIRS) criteria. -Early goal directed therapy: fluid resuscitation and antibiotics.
Dyspnea and/or chest pain Pneumonia31 -Patients with multiple medical co-morbidities and the immunosuppressed have an increased likelihood for the development of pulmonary infections. -Evaluate and address airway and breathing.

-Evaluate for signs/symptoms c/w sepsis or ARDS and treat appropriately.

Pericarditis32,33 -Viruses are the most common etiology in adults.

-Bacterial pericarditis disproportionately affects children.

-Viral pericarditis: NSAIDs therapy for 7-14 days following diagnosis.

-Bacterial pericarditis: Broad-spectrum antibiotics, and admit for further evaluation and treatment.

Infectious Endocarditis (IE)34 -Occurs most commonly in patients > 65 years of age, individuals with CHDs, and IVDAs.

Staphylococcus and Viridans streptococcus most common pathogens.

-Physical exam important in identifying vascular (septic pulmonary infarct, Janeway lesions, etc.) and immunologic phenomenon (osler nodes, roth spots, etc.)

-Diagnosed according to Duke Criteria

-Initiate broad-spectrum parenteral antibiotic therapy; patients require admission for evaluation and treatment.
Headache, back pain, or myalgias CNS Infection34,35 -Note: peds patients may present with hypothermia, hypoglycemia, poor feeding, seizures, irritability, bulging fontanelles.

-Pathogens of adult bacterial meningitis: S. pneumoniae, N. meningitides, H. influenza type B, Listeria monocytogenes.

-Pediatrics <2 months of age: Group B Streptococcus.

-Etiologies of viral meningitis: Enteroviruses (50%-75%).35

-Etiologies of encephalitis: herpes family viruses, varicella zoster virus, arboviruses (La Crosse virus, St. Louis virus, West Nile virus, Western Equine virus, Eastern Equine virus).

–HSV (frontal and temporal lobe involvement): taste and smell hallucinations, seizures; SIADH

–West Nile (anterior horn cell involvement): tremors, myoclonus, parkinsonism, flaccid paralysis

–La Crosse (cortical areas involved), most commonly in school-age children; late spring to fall: seizures, disorientation, focal neurologic signs)

–St. Louis (substantia nigra, pons, thalamus, cerebellum involved): tremor, ospoclonus, nystagmus, ataxia, SIADH and urinary symptoms (dysuria, urgency, incontinence)

–Eastern Equine (basal ganglia, thalamus, brainstem involvement), primarily in summer months: seizures


-CT before LP: immunosuppressed, history of CNS disease, new-onset seizure, focal neurologic deficit, papilledema, altered mental status


-Spinal epidural abscess: S. aureus indicated in 60-90% of cases.34

–Adults: often localize to the thoracic spine (50-80% of cases).34

–Pediatrics: abscesses localize to the cervical and lumbar spine.

-In the setting of bacterial meningitis => antibiotics.

–Dexamethasone for patients > 1 month of age to reduce neurologic sequelae.

-Acyclovir for viral encephalitis.


-Epidural abscess: broad-spectrum antibiotics.

–Consult neurosurg as soon as the diagnosis is suspected.


Mosquito-borne Illnesses36-40 -Dengue, Yellow Fever and Zika Viruses are arboviruses commonly transmitted by the mosquitos of the Aedes genus.

–Dengue outbreaks reported in Louisiana, Hawaii, Florida, and Texas.

—Presentation may include severe hemorrhagic diathesis, end-organ dysfunction, and hemodynamic collapse.  *Dx: PCR and serology.


–Yellow Fever: Endemic to Africa and Central America, rarely occurring in unvaccinated American travelers.

—Presentation ranges from subclinical infection to systemic disease (fever, jaundice, hemorrhage, and renal failure).  Dx: serology.


–Zika Virus: flavivirus closely related to dengue.  Unlike other arboviruses, Zika virus may also be transmitted through sexual contact and bodily secretions.  Local outbreaks have been reported in Florida.  A strong association between maternal Zika virus infection and fetal malformations has been identified.  Dx: PCR and serology.


–Chikungunya: Prevalent throughout Africa and Asia; first case identified in the U.S. was reported in Florida. Patients report high-grade fevers with disabling arthralgias.  Migratory polyarthritis with joint effusions (wrists, fingers, ankles) is common. Vesiculobullous eruptions and ulcers may be present. Dx: PCR


-Malaria: Endemic areas: Haiti, Dominican Republic, Mexico, central and South America, Areas of North and West Africa, India, Asia, and New Guinea.

–History should include discussion of clinical course: P vivax and P ovale cause relapses months after initial infection.

–Dx: thick and thin peripheral smears or PCR.

-Dengue: supportive care, transfusion if required.


-Yellow Fever: supportive care.


-Zika: Supportive care.  Pregnant patients in whom Zika virus infection is a concern should undergo serial ultrasounds (q 3-4 weeks) to identify potential anatomic abnormalities.


-Chikungunya:  Most often self-resolving. Rarely, neuro complications including seizures, meningo-encephalitis, and encephalopathy may occur (more common in children).


-Malaria: If suspected, begin treatment with chloroquine or mefloquine.

-If P vivax or P ovale are identified, chloroquine treatment should be followed by primaquine to eradicate the hypnozoite form.
















Acute Retroviral Infection41 -Males who have sex with males represent those at highest risk for HIV contraction.

-Half of all individuals infected with HIV manifest symptoms during the acute phase (fever, sweats, malaise, lethargy, headache, myalgias).

–Positive test results may not occur for up to 12 weeks post exposure (time to generate a detectable humoral response).

-Consensus guidelines support the strategy of offering antiretroviral therapy to anyone with HIV-related signs or symptoms.
Pharyngitis and dysphagia Epiglottitis42 -Pediatric epiglottitis rare in the U.S. secondary to H. influenza type B vaccination.

-Adult epiglottitis is commonly due to infection by S. pneumoniae, S. pyogenes, or N. meningitides.


-Definitive Dx: laryngoscopy or nasopharyngeal endoscopy.

–Pediatric patients: ideally performed in a controlled setting, immediately prior to securing the airway.

-Initiate antibiotic therapy with cefotaxime, ceftriaxone, or ampicillin-sulbactam.

–Add vancomycin if bacterial tracheitis cannot be excluded for S. aureus coverage

-Chemoprophylaxis recommended for household contacts of pediatric patients with suspicion of H. influenza type B epiglottitis.

Deep Space Infection43 -Peritonsillar abscess, Lemierre’s syndrome, retropharyngeal abscess, and Ludwig’s angina commonly present with fever, generalized malaise, sore throat, neck pain, and dysphagia.

S. aureaus is frequently the pathogen associated with retropharyngeal abscesses; anaerobes are uncommon.

-Lemierre’s syndrome, septic thrombophlebitis of the IJV, is associated with Fusobacterium necrophorum.



-Peritonsillar abscess: evaluate for uvular deviation.

-Cranial neuropathies may indicate contiguous spread of infection to the cavernous sinus.



–Stable patient: consider fiber-optic laryngoscopy.

–Concern for retropharyngeal abscess: AP and lateral neck radiographs. CT if able.

–Concern for peritonsillar abscess: CT neck with IV contrast or ultrasound with endocavitary probe.

–Lemierre’s syndrome or Ludwig’s angina: CT neck with IV contrast.

—CXR in the setting of Lemierre’s may reveal septic emboli.

-Initiate antibiotic therapy with directed activity against Streptococcus and oral anerobes.

-Retopharyngeal abscess: include S. aureaus coverage.

-Lemierre’s syndrome: metronidazole is first line.

-Most feared complications of deep space infections: airway compromise and mediastinitis.

Nausea, emesis, diarrhea GI Infections44  -Diverticulitis, diverticular abscess, and appendicitis may present with fever, nausea, emesis, and diarrhea.

-History and physical examination guide evaluation and management.

–Systemically ill patient with concern for complicated diverticulitis (requiring surgical evaluation and management) or those who are immunosuppressed, have numerous medical co-morbidities or are elderly: CT with IV and PO contrast: 100% sensitive in identifying pathology.44

-PO tolerant patient with uncomplicated diverticulitis: discharge home with antibiotic therapy.

-Complicated diverticulitis: fluid resuscitation, parenteral antibiotic therapy, and surgical consultation with consideration for IR if localized abscess.

-Colonoscopy required 3-6 weeks post resolution of diverticulitis/diverticular abscess.

-Appendicitis: fluid resuscitation, IV antibiotics, and surg consult.

GU Infections45  -High fever, abdominal pain, and nausea are the hallmarks of tubo-ovarian abscesses (TOAs) and salpingitis.

-The majority of TOAs result from salpingitis, both predominately associated with exposure to sexually transmitted infections (gonorrhea and chlamydia).

–Imaging: Ultrasound or CT with IV contrast are both highly sensitive for the diagnosis of TOA and salpingitis.45

 -Parenteral IV antibiotic therapy is indicated in patients with suspected salpingitis/TOA and should be continued until the patient is asymptomatic, has been afebrile for 24-48 hours, and laboratory studies demonstrate resolution of leukocytosis.45

*Dx: Diagnosis

The ED Approach

As the presentation of influenza is highly variable, the aforementioned infectious mimics must be considered.  In addressing syndromes characterized by fevers, myalgias, headache, cough, or sore throat, abdominal pain, emesis, or diarrhea the emergency physician should:

  • Address airway, breathing, and circulation as appropriate and intervene as necessary.
  • Make a determination regarding SIRS criteria and initiate early goal directed therapy as appropriate.
  • Perform a thorough history utilizing targeted questioning regarding medical comorbidities, immunization status, foreign travel, and sexual practices. Evaluate closely for risk factors for spinal abscess and endocarditis.
  • Perform a thorough physical exam to include a neurologic evaluation.
    • Focus on meningeal signs, pulmonary findings, rashes, etc.
  • Utilize the history and physical examination to make determinations regarding appropriate evaluation, treatment, and disposition.

Back to our case

An appropriate history has elicited medical comorbidities, an immunization deficiency, a sick contact, and the absence of recent travel.  A physical examination should be performed, focusing on the findings detailed above.  In terms of evaluating for influenza infection, the CDC recommends formal testing for our patient as he is > 50 years of age and possesses medical comorbidities.  If we utilize rapid antigen detection, and our patient is presenting during the height of influenza season (Dec-Feb), we must weigh the predictive value of a negative test as false negatives are likely to occur during this time frame.  If the rapid antigen test is positive, the patient is PO tolerant, and subsequent examination is otherwise without concerning signs/symptoms, the patient may be prescribed Tamiflu and discharged home.

Key Pearls

  • The presentation of influenza is variable => adults/adolescents report fevers, myalgias, headache, sore throat, etc. Pediatric patients commonly present with nausea and emesis.
  • Healthy adults/adolescents may receive a clinically accurate diagnosis of influenza during a local outbreak.
    • Consider the utility of rapid antigen testing during the peak of flu season
  • Influenza treatment is appropriate for patients presenting within 48 hours of the onset of symptoms and may reduce the duration of symptomatic illness by up to 1.6 days.25
  • Utilize a thorough history and physical exam to evaluate for infectious mimics of influenza.
    • Always begin by addressing the ABCs and do not hesitate to initiate early antibiotic therapy.


References / Further Reading

  1. Centers for Disease Control and Prevention. Emergency Department Visits. National Center for Health Statistics. 2011. Available from:
  2. Blaschke A, Shapiro D, Pavia T, Byington C, Ampofo K, Stockmann C, Hersh A. A national study of the impact of rapid influenza testing on clinical care in the emergency department. J Pediatric Infect Dis Soc. 2014; 3(2):112-118.
  3. Thompson W, Shay D, Weintraub E, et al. Influenza-associated hospitalizations in the United States. JAMA. 2004;292(11):1333-1340.
  4. The National Institute for Occupational Safety and Health (NIOSH). Seasonal Influenza (Flu) in the Workplace. 2016. Centers for Disease Control and Prevention. Available from:
  5. Marcellin L and Hessen M. Influenza. 2013. First Consult. Elsevier, Philadelphia. PA.
  6. Mazur L, Costello M. Influenza. 2017. (pp. 1072-1098). Henry’s Clinical Diagnosis and Management by Laboratory Methods. Elsevier, Inc. Philadelphia, PA.
  7. Treanor J. Influenza (Including Avian Influenza and Swine Influenza). 2015. (pp.2000-2024.e6). Principles and Practice of Infectious Diseases. Bennett J, Douglas R, and Blaser. Saunders, Philadelphia, PA.
  8. Taubenberger J, Morens D. The pathology of influenza virus infections. Annu Rev Pathol. 2008; 3:499-522.
  9. Centers for Disease Control and Prevention.Vaccination: Clinical Signs and Symptoms of Influenza. 2016. Available from:
  10. Surgees R, DeSousa C. Influenza virus associated encephalopathy. Arch Dis Child. 2006; 91(6):455-456.
  11. Craver RD, Sorrells K, and Gohd R: Myocarditis with influenza B infection. Pediatr Infect Dis J 1997; 16: pp. 629-630.
  12. Minodier L, Charrel R, Ceccaldi P, van der Werf S, Blanchon T, et al. Prevalence of gastrointestinal symptoms in patients with influenza, clinical significance and pathophysiology of human influenza fecal samples: what do we know? Virology Journal 2015; 12:215.
  13. Dolin R. Infectious disease. In: Braunwald E, et al., eds. Harrison’s Principles of Internal Medicine. 15th ed. New Yo1rk: McGraw-Hill, 2001:1125-1130
  14. Crum-Cianflone NF: Bacterial, fungal, parasitic, and viral myositis. Clin Microbiol Rev 2008; 21: pp. 473-494.
  15. Sanz-Esquerro J, De La Luna S, Ortin J, et al. Individual expression of the influenza virus PA protein induces degradation of coexpressed proteins. J Virol 1995; 69: pp. 2420-2426.
  16. Boivin G, Hardy I, Tellier G, et al. Predicting influenza infections during epidemics with use of a clinical case definition. Clin Infect Dis 2000; 31: pp. 1166-1169.
  17. Monto A, Gravenstein S, Elliott M, et al. Clinical signs and symptoms predicting influenza infection. Arch Intern Med 2000; 160: pp. 3243-3247.
  18. Grondahl B, Puppe W, Hoppe A, Kuhne I, Weigl JA, Schmitt HJ. Rapid identification of nine microorganisms causing acute respiratory tract infections by single-tube reverse transcription-PCR: feasibility study. J Clin Microbiol. 1999;37:1–7.
  19. Centers for Disease Control and Prevention.Vaccination: Who Should Do It, Who Should Not and Who Should Take Precautions. National Center for Health Statistics. 2016. Available from:
  20. Centers for Disease Control and Prevention. Guidance for clinicians on the use of RT-PCR and other molecular assays for the diagnosis of influenza virus infection. 2016. Available from:
  21. Centers for Disease Control and Prevention. Rapid diagnostic testing for influenza: Information for clinical laboratory directors. 2016. Available from:
  22. Centers for Disease Control and Prevention. Guidance on the Use of Influenza Antiviral Agents. 2016. Available from:
  23. Togo Y, Hornick R, Felitti V, Kaufman M, Dawkins A, Kilpe V, et al. Evaluation of therapeutic efficacy of amantadine in patients with naturally occurring A2 influenza. JAMA 1970;211:1149-1156.
  24. Wingfield W, Pollack D, Grunert R. Therapeutic effect of amantadine HCl and rimantadine HCl in naturally occurring influenza A2 respiratory illness in man. N Engl J Med 1969;281:579-584.
  25. Hayden F, Sperber S, Belshe R, Clover R, Hay A, Pyke S, et al. Recovery of drug-resistant influenza A during therapeutic use of rimantadine. Antimicrob Agents Chemother 1991;35:1741-1747.
  26. Centers for Disease Control and Prevention. Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009-2010 season. 2009. Available from:
  27. Centers for Disease Control and Prevention. Antiviral agents for the treatment and chemoprophylaxis of influenza: Recommendations of the advisory committee on immunization practices (ACIP). 2011. Available from:
  28. Hayden F, Osterhaus A, Treanor J, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza virus infections. GG167 Study Group. N Engl J Med. 1997; 337:874-880.
  29. Centers for Disease Control and Prevention. Influenza Antiviral Medications: Summary for Physicians. 2016. Available from:
  30. Puskarich MA. Emergency management of severe sepsis and septic shock. Curr Opin Crit Care 2012 Aug;18(4):295-300.
  31. Ellison R, Donowitz G. Acute Pneumonia. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Philadelphia: Saunders Elsevier, 2014:823-846
  32. Knowlton K, Narezkina A, Savoia M, Oxman M. Myocarditis and Pericarditis. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Philadelphia: Saunders Elsevier, 2014:106-1079.
  33. Troughton R, Asher C, Klein A. Pericarditis. Lancet. 2004; 363:717-727.
  34. Fowler V, Scheld M, Bayer A. Endocarditis and Intravascular Infections. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Philadelphia: Saunders Elsevier, 2014:990-1028.
  35. Singh A, Promes S. Key Points: Meningitis, Encephalitis, and Brain Abscess. In Emergency Medicine: Diagnosis and Management. 7th ed. Boca Raton: CRC Press, 2016: 1443-1453.e1
  36. Curtis S, Stobart K, and Vandermeer B. Clinical features suggestive of meningitis in children: a systematic review of prospective data. Pediatr. 2010; 126:952-960.
  37. Nigrovic L, Kupperman N, Macias C, et al: Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis. JAMA 2007; 297: 52-60.
  38. Scalera N and Ferri F. Spinal epidural abscess. 2012. First Consult. Elsevier, Philadelphia. PA.
  39. Richey L, Halperin J. Acute human immunodeficiency virus infection. Am J Med Sci. 2013; 345(2):136-142.
  40. Hammer S. Management of newly diagnosed HIV infection. N Engl J Med. 2005; 353:1702-1710.
  41. Richey L, Halperin J. Acute human immunodeficiency virus infection. Am J Med Sci. 2013; 345(2):136-142.
  42. Nayak J and Weinberg G. Epiglottitis. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Philadelphia: Saunders Elsevier, 2014:785-788.e1.
  43. Chian T and Prabaker K. Deep Neck Infections. In: ENT Secrets. Philadelphia: Saunders Elsevier, 2015: 20-25.
  44. Bope E and Fisher W. The Digestive System. In: Conn’s Current Therapy. Philadelphia: Saunders Elsevier, 2016:519-602.
  45. Soper D. Infections in the Female Pelvis. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Philadelphia: Saunders Elsevier, 2014:1372-1380.e2.

EM@3AM – Acute APAP Toxicity

Author: Erica Simon, DO, MHA (@E_M_Simon, EM Chief Resident, SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC, USAF)

Welcome to EM@3AM, an emdocs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

A 14 year-old male with a history of major depressive disorder presents to the emergency department following a toxic ingestion. The patient reports consumption of approximately 40 extra strength Tylenol caplets (500mg each), two hours prior to arrival. The patient is nauseated and covered in non-bloody gastric contents. Upon initial examination: GCS 15. VS: HR 132, BP 128/84, RR 18, SpO2 98% on room air.

What is the patient’s diagnosis? What’s the next step in your evaluation and treatment?

Answer: Acute Acetaminophen Toxicity1-3

  • Recommended dosing: 3-4g QD; toxic dose: 150mg/kg
  • Presentation varies according to stage of toxicity:
    • Stage 1 (0.5-24 hrs): mild nausea, emesis, weakness
    • Stage 2 (24-72 hrs): hepatotoxicity +/- nephrotoxicity => RUQ abdominal pain
    • Stage 3 (72-96 hrs): hepatotoxicity peaks => nausea, vomiting, jaundice, coagulopathy
    • Stage 4 (4 days -2 wks): recovery or decompensation resulting in death
  • Evaluation:
    • Use the Rumack-Matthew nomogram for single ingestions occurring <24 hours prior to arrival:
      • Obtain AST level at 4 hours s/p ingestion: utilize nomogram to determine the appropriateness of N-acetylcysteine (NAC) treatment
    • If the time of ingestion is unknown:
      • Obtain AST level and a serum acetaminophen level => if AST is elevated or serum acetaminophen concentration >10mcg/mL = initiate NAC2,3
  • Treatment:
    • If patient presents within one hour of toxic ingestion, consider NG lavage if no contraindications.
    • NAC Loading dose: 150 mg/kg IV (max 15g) infused over 1 hr or 140 mg/kg PO
  • Pearls:
    • Rumack-Matthew nomogram should not be employed in the setting of unknown time of ingestion or chronic acetaminophen therapy.
    • NAC is most effective if initiated within 8 hours of acetaminophen ingestion.
    • Evaluate for co-ingestions: serum salicylate, serum ETOH; calculate an anion gap and an osmolar gap as appropriate. Consider UDS.
    • End point of NAC treatment: AST <100 U/L and acetaminophen <10mcg/mL or if extended therapy required: normalization of INR, resolution of encephalopathy, and decreasing AST (<1,000 U/L).3


  1. Tintinalli J, Kelen G, Stapczynski J, Ma O, Cline D, et al. Tintinalli’s Emergency Medicine. 8th ed. New York: McGraw-Hill; 2016. Chapter 190, Acetaminophen.
  2. Heard K. Acetylcysteine for acetaminophen poisoning. N Engl J Med. 2008; 359(3):285-292.
  3. Mottram A, Kumar A. Focus On: Acetaminophen Toxicity and Treatment. American College of Emergency Physicians Clinical and Practice Management. Available from:—Practice-Management/Focus-On–Acetaminophen-Toxicity-and-Treatment/