All posts by Brit Long

Neurotrauma Resuscitation: Pearls & Pitfalls

Author: Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

A 24-year-old male arrives by EMS with a GCS of 5 after a severe MVC. He was ejected from the vehicle, and EMS placed a C-collar, followed by positioning on a backboard for transport. Bilateral IV’s were placed, and 1 L NS was started. They did not intubate him in the field, as they were 4 minutes from your hospital. What are your priorities in evaluation and management of this patient? What are the pearls and pitfalls in resuscitating the sick neurotrauma patient?

Neurotrauma, particularly traumatic brain injury (TBI), is a significant cause of death around the world and the leading cause of death in patients age 1 to 45 years.1-5 Approximately 78% of patients are managed in the emergency department (ED), with males and young adults the two primary populations affected.1.2 Traumatic neurologic injury not only causes an initial primary injury, but it is associated with several secondary insults.1-6

Some pathophysiology…

Cerebral perfusion pressure (CPP) is defined by the mean arterial pressure (MAP) minus the intracranial pressure (ICP). ICP is a function of the brain parenchyma, blood, and cerebrospinal fluid.2,7-12 The key is that an increase in one requires a decrease in another.2,7-12 Once compensatory methods are exhausted, further volume leads to drastic increases in ICP. Cerebral perfusion pressure is related to ICP, and increase in ICP may decrease cerebral perfusion. The ultimate goal of resuscitation and management of the neurotrauma patient is to ensure normal ICP, while preserving cerebral blood flow and perfusion.2,8,11,12

Are there physiologic goals?

Hypotension is associated with increased morbidity and mortality. A CPP goal of 50 to 70 mm Hg should be used, with SBP of at least 100 mm Hg (ages 50-69) and 110 mm Hg for 15-49 years and > 70 years, per the Brain Trauma Foundation.2,8,11-13  Otherwise, a MAP of 70-80 mm Hg is advised.5 Avoiding cerebral hypotension is recommended, though aggressive CPP targeting is not associated with improved outcomes.13-15 Hypoxemia also results in a significant increase in mortality. Key targets of resuscitation are shown below.

Goal Physiologic Parameters5,11,12
-Pulse oximetry > 94%, less than 100% (avoid hypoxemia and hyperoxemia)

-PaCO2 35-45 mm Hg

-SBP > 100 mm Hg (ages 50-69), and > 110 mm Hg (ages 15-49, > 70 years)

-pH 7.35-7.45

-ICP < 20 mm Hg

-Glucose 80-180 mg/dL

-CPP > 60 mm Hg

-Serum Na 135-145, (Hypertonic saline goal is 145-160)

-INR < 1.4

-Platelets > 75 x 103/mm3

-Hgb > 8 mg/dL

What are several dangerous secondary injuries?

Neurotrauma begins a cascade that may cause further cell death.8,11,12 The following are significant secondary injuries, all which increase adverse outcomes. Awareness of these injuries is necessary for prevention.5,8,11-15

– Hypotension: 30% of patients, resulting in higher likelihood of poor outcome (OR 2.67).2,8,11-15

– Hypoxia: 50% of patients, resulting in higher likelihood of poor outcome (OR 2.14).2,8,11-15

– Hyperoxia: PaO2 levels above 300-470 mm Hg are associated with worse outcome.2,8,11-15

– Fever: Elevated temperature worsens morbidity by secondary brain injury aggravation.2,13

– Coagulopathy: Associated with the traumatic event and may cause worsening of the neurologic injury and death. Acute TBI may cause coagulopathy itself through tissue factor and phospholipid release.16

– Glucose: Hyper- and hypoglycemia are predictors of poor neurologic status.2,8,11-15

Pearls in Evaluation and Management

Focus on airway, breathing, circulation, disability, and exposure in the primary survey, with spinal precautions.2,11,17-20 Avoid secondary complications, and other markers of worse outcome include poor GCS motor score, pupillary dysfunction, and increased ICP. Abnormal pupillary response and altered motor function are markers for severe brain trauma, as is posturing. Decorticate posturing (arm flexion and leg extension) is due to injury above the midbrain, and decerebrate posturing (arm extension and internal rotation, wrist and finger flexion, leg internal rotation and extension) is a sign of more caudal injury involving the midbrain.11,12,17 Abnormal pupils, decreased mental status, abnormal GCS, penetrating injury, abnormal motor status, and severe injury require neuroimaging.  Severe neurotrauma requires consultation with neurosurgery.2,11,12,17  This post will focus on the hypotensive patient with neurologic injury.

ED Considerations
-Maintain spinal precautions

-Conduct primary and secondary surveys; address life-threatening injuries

-Advanced airway management may be needed for airway protection, hypoxia, and control of ventilation

-Obtain rapid IV access

-Optimize oxygenation, blood pressure, and ventilation

-Target oxygen saturation > 94%, with systolic blood pressure > 100-110 mm Hg

– Focused neuro exam: GCS, motor function, and pupillary function

-Obtain head CT noncontrast

-Any sign of worsening neurologic status warrants hyperosmolar therapy

Tiers of ICP management, per the Brain Trauma Foundation, are shown below.11,12,17 We will discuss pearls and subtleties for these therapies, but first, let’s discuss airway.

Tier Options
0 -Head of bed elevation

-Control fever, pain, and agitation

-Optimize physiologic parameters such as blood pressure and oxygen

-Target PaCO2 to 35-38 mm Hg

1 -Osmotic therapy includes mannitol, hypertonic saline, or sodium bicarbonate

-External ventricular drainage system should be placed if acute obstruction is present

2 -Propofol drip titration

-Optimize other parameters

3 -Barbiturate coma

-Surgical decompression if ICP refractory to treatment

-Therapeutic hypothermia

-Moderate hyperventilation (only if active herniation)

How should the airway be managed?

Airway protection and blood pressure support for severe neurotrauma are priorities, and first pass success is vital. Rapid sequence intubation with in-line stabilization of the cervical spine may be necessary.2,11,18-20 Preoxygenation is important to avoid desaturation, so start your NO DESAT interventions early.21,22

Intubation Considerations
-Preparation: Proper positioning, preoxygenate, and use apneic oxygenation with nasal cannula, facemask, or noninvasive positive pressure ventilation

-Elevate head of bed to improve CPP and decrease aspiration

-Premedication regimens are controversial. Fentanyl at 2-5 micrograms/kg IV or esmolol 1.5mg/kg IV may decrease catecholamine surge and control the hemodynamic response to intubation

-Induction agent may include ketamine (does not adversely affect patients with neurotrauma) and etomidate – these agents have less hemodynamics effects

-Propofol has neuroprotective effects, but hypotension may occur

-Post intubation analgesia and sedation are essential – have your drips ready to go at the time of intubation


Up to 80% of patients may experience a hypertensive response to laryngoscopy or suctioning, and lidocaine was initially thought to blunt this. However, lidocaine has not demonstrated ability to reduce ICP or improve neurologic outcome.18-20,23 Fentanyl at doses of 2-5 micrograms/kg IV prior to intubation can reduce the hyperdynamic response to intubation, as can esmolol at 1.5 mg/kg IV. However, esmolol should be avoided in patients with hypotension, hemorrhagic shock, or signs of multiple trauma.18-20,24


Traditionally, ketamine was contraindicated for induction in intubation in TBI, but literature suggests that not only is it safe, but it may be beneficial. Ketamine improves cerebral blood flow, and evidence suggests it does not raise ICP.19,25  Propofol has high lipid solubility and rapid onset of action that can reduce ICP and oxidative stress. However, it may cause hypotension.19,20,26 Etomidate may result in less hypotension and cardiac dysfunction. It can reduce ICP and maintain CPP, but it also may lower the seizure threshold and increase the risk of vomiting and myoclonic movements.19,27 The key for an induction agent is utilizing lower doses in patients with hypotension, as any agent at full dose will worsen hypotension.


Paralysis is essential to improve first pass success including succinylcholine or rocuronium. Succinylcholine allows faster time to recovery and assessment of neurologic status, as rocuronium will last longer. Ultimately, the choice of paralytic rests on the physician, as both are safe and efficacious.19,20  However, defasciculating doses of paralytics such as succinylcholine or pancuronium are not beneficial and do not reduce ICP.19,20

Post Intubation

Post intubation sedation and analgesia are an absolute must.18-20 An intubated patient with inadequate analgesia and sedation may experience increased ICP due to sympathomimetic response.24 The key is to order your post intubation meds at the same time as your paralytic and induction agent.18-20 Analgesics including fentanyl and remifentanil are fast and predictable. Morphine and hydromorphone may accumulate with prolonged infusion, though they do have longer duration of action. Sedative medications include propofol, which possesses fast onset and offset, allowing for repeat neurologic assessment.  If used keep close tabs on blood pressure. Infusion, rather than bolus doses, will mitigate the risk of decreasing BP. Benzodiazepines can be used, though they can reduce BP and respiratory status. However, they do reduce cerebral blood flow and ICP.28 Unfortunately, tolerance may develop, and reassessment is difficult due to metabolite accumulation. The new kid on the block, dexmedetomidine, is a selective alpha-2 receptor agonist with anxiolytic and sedative effects.19,29 Hypotension and bradycardia are the most common side effects, most commonly seen with bolus dosing. It may reduce ICP, though further study is needed.

Avoid hypoxia post intubation, targeting O2 saturation 94%-98%. Hyperoxia with PaO2 greater than 300-470 mm Hg is discouraged due to worse outcomes.13,18-20  Unless actively herniating, hyperventilation is not recommended. PaCO2 levels of 35 to 45 mm Hg, or end-tidal CO2 30 to 40 mm Hg, are your goals.2,11,18

What about hypotension?

Hypotension increases mortality two-fold, specifically any SBP drop less than 90 mm Hg.2,11-15,19 The polytrauma patient with head trauma can be difficult.  These patients are often hypotensive, and permissive hypotension is not recommended. Target a SBP of at least greater than 100 mm Hg (for patients 50-69 years of age) or 110 mm Hg (for those 15-49 years and > 70 years).11 Keep in mind that ATLS states a MAP > 80 mm Hg in patients with severe TBI is reasonable.5 Start first with fluids, specifically normal saline or blood.2,11,18 Avoid hypo-osmotic fluids, which can increase cerebral edema and ICP.30  Albumin is associated with higher mortality, which was demonstrated in the SAFE trial in TBI patients.31 Literature suggests no difference between normal saline and HTS for patients with no signs of herniation.30

Wait, what’s this about neurogenic shock?

Neurogenic shock occurs with injury above T6 and is a form of distributive shock. It is caused by loss of sympathetic tone.32-35 Patients may show low HR and BP; however, hypovolemic shock must first be ruled out in the trauma patient. Spinal shock is different, with loss of sensation and motor function below the spinal cord injury. Reflexes are often depressed below the injury level.32-35

Are vasopressors needed?

A SBP of at least 100-110 mm Hg is recommended by the Brain Trauma Foundation, as hypotension increases morbidity and mortality.11 Specifically in neurogenic shock with hypotension and bradycardia, fluids and vasopressors will be needed.32,33 Loss of sympathetic tone is common within the first week of injury.6,32-35 A goal MAP of 85 mm Hg is recommended by the AANS and CNS in neurogenic shock.35  Dopamine, norepinephrine, or phenylephrine may be used.  Norepinephrine will increase afterload and inotropy, needed with the loss of sympathetic tone.  Phenylephrine will improve vascular tone and can be used in patients who are not bradycardic.6,33-35

What hyperosmolar therapies are available?

Hyperosmolar therapy is a foundation of management. These measures can reduce ICP and improve cerebral blood flow.2,12,17,18  Hyperosmolar agents should be used with signs of increased ICP, pupillary change, decrease in GCS > 2 points, or posturing.2,12,17,18   Agents include 20% mannitol 0.25-1 g/kg IV as a rapid infusion over 5 minutes or 3% NaCl 150 ml IV over 10 minutes (HTS 23.4% 30mL can be used through central line).2,11,17,18,30,36-38 We will discuss these agents further, but keep in mind that if hypotension is a concern, HTS may be a better resuscitation fluid.5,17,18  For ICP reduction, a 2015 meta-analysis finds no difference in neurologic outcome or mortality between mannitol and HTS.30

  1. Mannitol

Mannitol is administered as a 20% solution.2,30,36-38 This solution deforms RBCs and decreases blood viscosity, improving cerebral blood flow.36-38  A major consideration is autoregulation and the presence of intact Blood-Brain-Barrier, as if these are intact, ICP will decrease. If not intact, mannitol may worsen outcomes.11,18,30 Rebound increases in ICP can occur, and the solution may cause renal injury through excess diuresis. IV fluids are necessary when providing mannitol, along with Foley catheter.11,17,18

  1. HTS

HTS concentrations range from 2% to 23.4%, which also improves cerebral blood flow and reduces parenchymal water content.2,11,12,17 HTS can improve blood pressure as a volume expander. The risk of rebound ICP is less than that of mannitol.2,11,17,18,30 The most common side effect of HTS is hyperchloremic metabolic acidosis.2,18,30

What about ocular US for increased ICP?

Ultrasound can measure optic nerve sheath diameter (ONSD), which correlates closely with ICP.18,39,40 The normal optic nerve sheath is up to 5 mm in diameter, and ONSD will increase with elevated ICP. ONSD should be measured 3 mm posterior to the globe for both eyes, with an average between measurements. Values greater than 5 mm predict increased ICP, with sensitivity and specificity greater than 90%.39,40

When is surgery required?

Surgical management of TBI may be needed to repair depressed skull fracture or evacuate intracranial mass (such as blood).2,11,17,18 Decompressive craniectomy is indicated for refractory intracranial hypertension; however, decompressive craniectomy may not improve functional outcome while decreasing ICP, as shown in the DECRA trial.41-45 Ultimately, your neurosurgeon will make this decision, but they must be on board early in the patient’s management.11,45

Is hypothermia effective in neurotrauma?

Studies have not found an improvement in mortality or neurologic status with hypothermia in neurotrauma.2,11,18,46,47 However, hypothermia can reduce intracranial hypertension.46,47 Targeted management of temperature reduces cerebral metabolic rate and release of excitatory neurotransmitters, but more study is required.11,46,47

Should you reverse coagulopathy with traumatic intracerebral hemorrhage?

Coagulopathy is common, as close to 1/3 of patients with TBI display a coagulopathy, due to patient medication or release of tissue factor causing consumptive coagulopathy.11,16 Coagulation panel and TEG can be helpful, with reversal dependent on results and patient medication. Vitamin K, PCC/FFP, and novel antidotes can be utilized.11,48-50 We will not go into detail here on reversal. However, keep in mind that platelet transfusion in patients on antiplatelet medication with ICH may be harmful per the recent PATCH trial.51

What is the role of pharmacologically-induced coma?

Barbiturates can be used to reduce ICP, if refractory to other treatment, through suppression of cerebral metabolism, modification of vascular resistance, and decrease of neuronal excitotoxicity.2,18,52,53 However, barbiturates have significant side effects, as one in four experiences hypotension.2,11,53 A 2012 Cochrane Review found no change in outcomes for severe TBI with barbiturate coma.53

Corticosteroids used to be recommended, but what about today?

The CRASH trial suggests worse outcomes and increased mortality for patients with TBI given steroids.54-57 In the setting of spinal cord injury, the American Association of Neurologic Surgeons and Congress of Neurologic Surgeons do not recommend steroids.2,6,11

Should seizures be treated in neurotrauma?

Early posttraumatic seizures occur within 7 days of injury, with late seizures beyond 7 days.2,11,58,59 Seizures occur in up to 30% of TBI patients (50% of patients with penetrating injury).2,58,59 With seizures increasing ICP, any active seizure requires immediate treatment, with benzodiazepines first line. Prophylaxis on the other hand is more controversial. The presence of any risk factor including include GCS < 10, cortical contusion, any intracranial hematoma, depressed skull fracture, penetrating head injury, or seizure within 24 hours of injury requires prophuulaxis.11,58,59 Otherwise, prophylaxis is not recommended. Levetiracetam is equivalent to phenytoin for seizure reduction, and it is associated with less risk of side effect.58,59

Does tranexamic acid have a place in neurotrauma?

The CRASH-2 and MATTERs studies have suggested survival benefit within three hours of trauma for TXA.60,61 The CRASH-2 Intracranial Bleeding Study found a trend towards reduction in intracranial hemorrhage growth and lower mortality in patients with traumatic hemorrhage, with another study finding reduction in hemorrhage growth.60,62 CRASH-3 is underway, evaluating TXA in TBI specifically.63

Pitfalls in evaluation and management

Several medications have not demonstrated improvement in outcomes for TBI, including progesterone, magnesium, hyperbaric oxygen, and cyclosporine.2,11,64,65

Hyperventilation can reduce ICP for short periods.2,11,18,66,67 However, hyperventilation may result in secondary ischemia if used for prolonged periods and increases the risk of cerebral edema. Hyperventilation has demonstrated worse clinical outcomes in patients hyperventilated to PaCO2 less than 30 mm Hg for six hours up to five days.18,66,67 Mild hyperventilation can be used for acute worsening, but only for a short period, targeting PaCO2 30-35 mmHg.2,11,18

Key points

– Neurotrauma is common, as it is the leading cause of death in North America in those between ages 1 year to 45 years. Primary and secondary injuries result in severe morbidity and mortality.

– Neurotrauma includes head contusion, epidural hematoma, subdural hematoma, subarachnoid hemorrhage, diffuse axonal injury, skull fracture, and traumatic spinal cord injury.

– Cerebral perfusion pressure requires adequate cerebral blood flow.

–  Evaluation and management in the emergency department entails initial stabilization and resuscitation while assessing neurologic status.

– Targeting mean arterial pressure, oxygen levels, and neurologic status are key components. ICP management should follow a tiered approach.

Intubation of the patient with neurotrauma should be completed with several considerations.

– Hyperosmolar treatments include HTS and mannitol.


References/Further Reading

  1. Faul M, Xu L, Wald MM, et al. Traumatic brain injury in the United States: emergency department visits, hospitalizations and deaths 2002–2006. Atlanta (GA): Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2010.
  2. Wan-Tsu WC, Badjatia N. Neurotrauma. Emerg Med Clin N Am 2014;32:889-905.
  3. Rutland-Brown W, Langlois JA, Thomas KE, Xi YL. Incidence of traumatic brain injury in the United States, 2003. J Head Trauma Rehabil 2006; 21:544.
  4. Stein DM, Roddy V, Mark J, Smith WS, Weingart SD. Emergency Neurological Life Support: Traumatic Spine Injury. Neurocrit Care 2012;17:S102-S111.
  5. ATLS Subcommittee; American College of Surgeons’ Committee on Trauma; International ATLS working group. Advanced trauma life support (ATLS®): the ninth edition. J Trauma Acute Care Surg. 2013 May;74(5):1363-6.
  6. Hadley MN, Walters BC, Aarabi B, et al. Guidelines for the management of acute cervical spine and spinal cord injuries. Neurosurgery 2013;72(Suppl 2): 1–259.
  7. Oddo M, Le Roux PD. What is the etiology, pathogenesis and pathophysiology of elevated intracranial pressure? In: Neligan P, Deutschman CS, editors. The evidenced based practice of critical care. Philadelphia: Elsevier Science; 2009.
  8. Swadron SP, LeRoux P, Smith WS, Weingart SD. Emergency Neurological Life Support: Traumatic Brain Injury. Neurocrit Care 2012;17:S112–S121.
  9. Bouma GJ, Muizelaar JP. Cerebral blood flow, cerebral blood volume, and cerebrovascular reactivity after severe head injury. J Neurotrauma 1992; 9 Suppl 1:S333.
  10. Bouma GJ, Muizelaar JP, Bandoh K, Marmarou A. Blood pressure and intracranial pressure-volume dynamics in severe head injury: relationship with cerebral blood flow. J Neurosurg 1992; 77:15.
  11. Carney N, Totten AM, O’Reilly C, Ullman JS, Hawryluk GWJ, bell MJ, et al. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery 2016;0(0):1-10.
  12. Stevens RD, Huff JS, Duckworth J, et al. Emergency neurological life support: intracranial hypertension and herniation. Neurocrit Care 2012;17(Suppl 1):S60–5.
  13. McHugh GS, Engel DC, Butcher I, et al. Prognostic value of secondary insults in traumatic brain injury: results from the IMPACT study. J Neurotrauma 2007; 24:287.
  14. Chestnut RM, Marshall LF, Klauber MR, et al. The role of secondary brain injury in determining outcome from severe head injury. J Trauma 1993;34(2):216-22.
  15. Marmarou A, Anderson RL, Ward JD, et al. Impact of ICP instability and hypotension on outcome in patients with severe head trauma. J Neurosurg 1991; 75(Suppl):S59–66.
  16. Harhangi BS, Kompanje EJ, Leebeek FW, Maas AI. Coagulation disorders after traumatic brain injury. Acta Neurochir (Wien) 2008; 150:165.]
  17. Emergency Neurological Life Support: Elevated ICP or Herniation. 2014. Available at Accessed 16 November 2016.
  18. Weingart S. EMCrit: Podcast 78 – Increased intra-cranial pressure (ICP) and herniation, aka brain code. Available at Accessed 16 November 2016.
  19. Bucher J, Koyfman A. Intubation of the Neurologically Injured Patient. JEM 2015;49(6):920-7.
  20. Seder DB, Riker RR, Jagoda A, Smith WS, Weingart SD. Emergency Neurological Life Support: Airway, Ventilation, and Sedation. Neurocrit Care 2010;17:S4-S20.
  21. Weingart SD, Levitan RM. Preoxygenation and prevention of desaturation during emergency airway management. Ann Emerg Med 2012;59:165–1751.
  22. Dixon BJ, Dixon JB, Carden JR, et al. Preoxygenation is more effective in the 25 degrees head-up position than in the supine position in severely obese patients: a randomized controlled study. Anesthesiology 2005;102:1110–5. discussion 1115A.
  23. Robinson N, Clancy M. In patients with head injury undergoing rapid sequence intubation, does pretreatment with intravenous lignocaine/lidocaine lead to an improved neurological outcome? A review of the literature. Emergency Medicine Journal : EMJ. 2001;18(6):453-457. doi:10.1136/emj.18.6.453
  24. Dahlgren N, Messeter K. Treatment of stress response to laryngoscopy and intubation with fentanyl. Anaesthesia 1981;36:1022–6.
  25. Cohen L, Athaide V, Wickham ME, Doyle-Waters MM, Rose NG, Hohl CM. The effect of ketamine on intracranial and cerebral perfusion pressure and health outcomes: a systematic review. Ann Emerg Med 2015;65:43–51.
  26. Rossaint J, Rossaint R, Weis J, et al. Propofol: neuroprotection in an in vitro model of traumatic brain injury. Crit Care 2009; 13:R61.
  27. Moss E, Powell D, Gibson RM, McDowall DG. Effect of etomidate on intracranial pressure and cerebral perfusion pressure. Br J Anaesth. 1979;51:347–52.
  28. Barrientos-Vega R, Mar Sanchez-Soria M, Morales-Garcia C, Robas-Gomez A, Cuena-Boy R, Ayensa-Rincon A. Prolonged sedation of critically ill patients with midazolam or propofol: impact on weaning and costs. Crit Care Med. 1997;25:33–40.
  29. Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine vs. midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012;307:1151–60.
  30. Boone MD, Oren-Grinberg A, Robinson TM, Chen CC, Kasper EM. Mannitol or hypertonic saline in the setting of traumatic brain injury: What have we learned? Surgical Neurology International. 2015;6:177.
  31. The SAFE Study Investigators. A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit. N Engl J Med 2004; 350:2247-2256.
  32. Jia X, Kowalski RG, Sciubba DM, Geocadin RG. Critical care of traumatic spinal cord injury. J Intensive Care Med 2013; 28:12.
  33. Blood pressure management after acute spinal cord injury. Neurosurgery 2002; 50:S58.
  34. Ditunno JF, Little JW, Tessler A, Burns AS. Spinal shock revisited: a four-phase model. Spinal Cord 2004; 42:383.
  35. Guidelines for the management of Acute Cervical Spine and Spinal Cord Injuries: %20Meetings/*/media/Files/Education%20and%20Meetingf/ Clinical%20Guidelines/TraumaGuidelines.ashx (2007). Accessed May 2016.
  36. Vialet R, Albanèse J, Thomachot L, et al. Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5% saline is more effective than 2 mL/kg 20% mannitol. Crit Care Med 2003; 31:1683.
  37. Kassell N, Baumann K, Hitchon P, et al. The effects of high dose mannitol on cerebral blood flow in dogs with normal intracranial pressure. Stroke 1982;13(1): 59–61.
  38. Mendelow AD, Teasdale GM, Russell T, et al. Effect of mannitol on cerebral blood flow and cerebral perfusion pressure in human head injury. J Neurosurg 1985; 63(1):43–8.
  39. Sekhon MS, McBeth P, Zou J, et al. Association between optic nerve sheath diameter and mortality in patients with severe traumatic brain injury. Neurocrit Care. 2014;21(2):245-252.
  40. Hassen GW, Bruck I, Donahue J, et al. Accuracy of optic nerve sheath diameter measurement by emergency physicians using bedside ultrasound. J Emerg Med. 2015;48(4):450-457.
  41. Bullock MR, Chestnut R, Ghajar J, et al. Guidelines for the surgical management of traumatic brain injury. Neurosurgery 2006;58(Suppl)S2-1-3.
  42. Cooper DJ, Rosenfeld JV, Murray L, et al. Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med 2011;364(16):1493–502.
  43. Honeybul S, Ho KM, Lind CR. What can be learned from the DECRA study. World Neurosurg 2013;79(1):159–61.
  44. Sahuquillo J, Martinez-Ricarte F, Poca MA. Decompressive craniectomy in traumatic brain injury after the DECRA trial. Where do we stand? Curr Opin Crit Care 2013;19(2):101–6.
  45. Hutchinson PJ, Kolias AG, Timofeev IS, Corteen EA, Czosnyka M, Timothy J, et al. Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension. N Engl J Med. 2016 Sep 7. [Epub ahead of print].
  46. Sydenham E, Roberts I, Alderson P. Hypothermia for traumatic head injury. Cochrane Database Syst Rev 2009;(2):CD00104.
  47. Clifton GL, Valadka A, Zygun D, et al. Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. Lancet Neurol 2011;10(2):131–9.
  48. Morgenstern LB, Hemphill JC 3rd, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010; 41:2108.
  49. Eller T, Busse J, Dittrich M, et al. Dabigatran, rivaroxaban, apixaban, argatroban and fondaparinux and their effects on coagulation POC and platelet function tests. Clin Chem Lab Med 2014; 52:835.
  50. Dickneite G, Hoffman M. Reversing the new oral anticoagulants with prothrombin complex concentrates (PCCs): what is the evidence? Thromb Haemost 2014; 111:189.
  51. Baharoglu MI, Cordonnier C, Al-Shahi Salman R, de Gans K, Koopman MM, Brand A, Majoie CB. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial. 2016 Jun 25;387(10038):2605-13.
  52. Eisenberg HM, Frankowski RF, Contant CF, et al. High-dose barbiturate control of elevated intracranial pressure in patients with severe head injury. J Neurosurg 1988;69(1):15–23.
  53. Roberts I, Sydenham E. Barbiturates for acute traumatic brain injury. Cochrane Database Syst Rev 2012;(12):CD000033.
  54. Roberts I, Yates D, Sandercock P, et al. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet 2004;364(9442): 1321–8.
  55. Bracken M, Shepard M, Collins W, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 1990; 322(20):1405–11.
  56. Bracken MB, Shepard MJ, Holford TR, et al. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. JAMA 1997;277(20):1597–604.
  57. Bracken M. Steroids for acute spinal cord injury. Cochrane Database Syst Rev 2012;(1):CD001046.
  58. Inaba K, Menaker J, Branco BC, et al. A prospective multicenter comparison of levetiracetam versus phenytoin for early posttraumatic seizure prophylaxis. J Trauma Acute Care Surg 2013;74(3):766-71 [discussion: 771-3].
  59. Torbic H, Forni A, Anger KE, et al. Use of antiepileptics for seizure prophylaxis after traumatic brain injury. Am J Heal Pharm 2013;70(9):759–66.
  60. Roberts I, Shakur H, Coats T, Hunt B, Balogun E, Barnetson L, Cook L, Kawahara T, et al. The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol Assess. 2013 Mar;17(10):1-79.
  61. Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. 2012 Feb;147(2):113-9.
  62. Perel P, Al-Shahi Salman R, Kawahara T, Morris Z, Prieto-Merino D, Roberts I, Sandercock P, et al. CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) intracranial bleeding study: the effect of tranexamic acid in traumatic brain injury–a nested randomised, placebo-controlled trial. Health Technol Assess. 2012;16(13):iii-xii, 1-54.
  63. Dewan Y, Komolafe EO, Mejía-Mantilla JH, Perel P, Roberts I, Shakur H. CRASH-3 – tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial. Trials. 2012;13:87.
  64. Wright DW, Yeatts SD, Silbergleit R, et al. Very Early Administration of Progesterone for Acute Traumatic Brain Injury. N Engl J Med 2014;371(26):2457-2466.
  65. Skolnick BE, Maas AI, Narayan RK, van der Hoop RG, et al; SYNAPSE Trial Investigators. A clinical trial of progesterone for severe traumatic brain injury. N Engl J Med 2014 Dec 25;371(26):2467-76.
  66. Coles JP, Minhas PS, Fryer TD, et al. Effect of hyperventilation on cerebral blood flow in traumatic head injury: clinical relevance and monitoring correlates. Crit Care Med 2002; 30:1950.
  67. Coles JP, Fryer TD, Coleman MR, et al. Hyperventilation following head injury: effect on ischemic burden and cerebral oxidative metabolism. Crit Care Med. 2007;35:568–78.

FOAMed Resources Part IX: Residency Program-Sponsored FOAMed

Author: Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

Welcome back to the FOAMed Resource Series with Part IX. We have discussed a wide variety of topics including critical care, ultrasound, pediatrics, and toxicology. Today we focus on FOAMed coming to you from residency programs. These sites provide some of the best education out there, so hold on tight for more great educational content!



CORE EM comes straight from FOAMed heavyweight Anand Swaminathan and the NYU EM program. This site focuses on yep, you guessed it, core content. The site provides regular blogposts (including cases, journal club, and core topics), videos, as well as a podcast. It provides free, bread and butter education that is second to none.




Taming the SRU (Shock Resuscitation Unit) from Cincinnati is another major contributor to core content. The site contains a blog focusing on several aspects of emergency medicine including procedures, ultrasound, cases, core content, and education. The site is associated with a podcast, and the “Annals of B-Pod” are downloadable journal-type articles on interesting cases and conditions.




Brown Emergency Medicine publishes great content on cases, core topics, journal reviews, procedural videos, images, and controversial topics in EM. Asynchrony EM is a FOAMed-guided tour of EM topics. The site also has an overview of 52 classic articles in EM.




UMEM education pearls provide almost daily updates on classic EM topics and cutting edge research. The site is easy to use and follow, and all posts are referenced so you can gather more information if needed. The UMEM educational hub contains video lectures from some of the best in EM and critical care –




The residents of Kings County Hospital ED bring you an up-to-date, evidence-based blog on board review topics, ECGs, clinical cases, critical care, toxicology, pediatrics, radiology, and many others. Content is almost released daily, and oh yeah, they have lectures from grand rounds for those visual learners.




Washington University in St. Louis has put together a great combination of FOAMed content. This sites contains case-based learning, FOAM supplement (a combination of great FOAMed topics), EMS cases (brought in by ambulance), consultant teachings, challenging cases, and classic and challenging ECGs. The residency’s journal club is also available, with discussions on key topics vital to everyday practice.




NUEM comes from Northwestern University EM. This blog contains content on new literature, dogma in EM, and interesting cases, broken down by organ system. Each post is well written and referenced, as well as peer reviewed by a staff expert in the subject.




Sinai EM is a great blog that provides several posts per week focusing on imaging, cases, controversy, and literature updates. The vast majority of EM content is well represented. They also cover the core literature, focusing on one article in one week.




Carolinas Core Concepts comes from the CMC EM residency program. The blog contains several categories, each providing valuable content. Core Concepts provides you with the basics for success in EM through bullet point reviews. The site also contains resident driven blogs including ortho, cardiology, tox, and peds, as well as attending blogs on coding/billing, ultrasound, and health policy.




EM DAILY from Cooper University Health Care gives you great educational pearls. Every day of the week focuses on a specific topic, with basics on Monday, advanced techniques on Tuesday, radiology on Wednesday, conference on Thursday, critical care on Friday, Wellness on Saturday, along with several others. A weekly summary is provided on Sunday for those who desire an all-in-one stop.




The EMBlog from the Mayo Clinic EM Program provides a platform for FOAMed focusing on new and controversial studies, resident education, social medicine, shared decision making, and disposition. This blog’s strength is in its coverage of topics not covered elsewhere in FOAMed, specifically the social aspects of our care in the ED. You don’t want to miss this resource.




Las Vegas EMR contains posts including bread and butter topics in EM, while also evaluating myths and dogma in daily EM practice. Conference videos on lectures are provided on the site, giving learners of all levels access to more content. All posts are well referenced as well.




HQMedED comes from Hennepin County Medical Center. This site is a collection of online videos and lectures on EM topics ranging from procedures, ECG, pediatrics, critical care, and toxicology, as well as core content. This is a great resource for visual learners.




The Temple EM Residency blog provides regular updates in common EM topics through an evaluation of the most current literature. Posts are provided at least once per week, though more commonly this occurs several times per week. If you want to stay up to date on relevant literature, this is the blog for you.

This is not an all-encompassing list, and if you like other resident-run blogs, please comment below! Stay tuned for more in the series.

Sepsis Biomarkers: What’s New?

Author: Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

A 43-year-old female presents with cough, congestion, wheezing, fever, and myalgias. She has a history of hypertension and recurrent UTI. She tried to overcome her symptoms with acetaminophen and oral fluids, but her symptoms have worsened. Her vital signs include RR 23, HR 102, BP 102/63, T 101.2, and Saturation 94% on RA. She has right-sided crackles on exam and appears ill, with dry mucosa. You start one liter of LR, while ordering CBC, renal panel, lactate, urinalysis, and chest Xray. Her chest Xray and urinalysis are negative, but after 1L LR, she still appears ill. The lactate returns at 4.2, and you start IV antibiotics with concern for septic shock. Your medical student on shift asks about using procalcitonin to rule out a bacterial cause of sepsis. You know about lactate, but are there other markers you can use in sepsis?

Sepsis is common in the ED and a major cause of morbidity and mortality. The body’s response to an infectious source in sepsis often results in dysregulated immune response, and current diagnosis relies on physiologic criteria and suspicion for a source of infection with laboratory and imaging studies. The host response triggered by the infection can be measured using several biomarkers.1-4

Biomarkers are defined by laboratory assessments used to detect and characterize disease, and they may be used to improve clinical decision-making. Through the years, complete blood cell count (CBC), troponin, creatine kinase (CK), lactate, C-reactive protein (CRP), ESR, and myoglobin have been advocated as biomarkers for a long list of conditions. However, what do biomarkers offer in sepsis? Some argue these biomarkers lack sufficient sensitivity outside of history and exam, while others state these markers can drastically improve medical decision making. In sepsis, diagnosis may not be easy, and a reliable biomarker may be able to improve early diagnosis, risk stratification, assessment of resuscitation, and evaluation.4-8

The post will evaluate several key biomarkers including lactate, procalcitonin, troponin, and novel lab assessments.


Lactate can be used in sepsis for resuscitation and severity stratification. It is normally produced in tissues due to pyruvate and NADH metabolism. There are several causes of lactate elevation, and not all are due to shock. Excess beta activity, inflammatory mediators, and liver disease may increase lactate.8-13  The table below demonstrates types and sources of lactate production.

Type A Type B1

Associated with disease

Type B2

Drugs and Toxins

Type B3

Associated with inborn errors of metabolism

Tissue Hypoperfusion


Anaerobic muscular activity


Reduced tissue oxygen delivery







Thiamine deficiency




Hepatic or renal failure


Short bowel syndrome







Lactate-based dialysate fluid



Alcohols: Methanol, Ethylene Glycol







Anti-retroviral agents

Pyruvate carboxylase deficiency


Glucose-6-phosphatase deficiency


Fructose-1,6-bisphosphatase deficiencies


Oxidative phosphorylation enzyme defects


The Surviving Sepsis Campaign recommends lactate for screening.1 Point of care (POC) lactate can be used for this screen, with specificity of 82% for lactate > 2 mmol/L. However, POC lactate has sensitivity of 30-40%, thus physicians must consider the clinical picture and patient appearance.11-16 Arterial blood is not required for this screening, and a venous blood gas (VBG) is fast and easily obtainable. As long as analysis occurs within 15 minutes of sampling, no effect from tourniquet or room temperature is observed.16,17 Lactate is not as reliable if the sample is run over 30 minutes from the time the sample is obtained.


As lactate elevates, mortality increases. In patients with lactate greater than 2.1 mml/L, mortality approximates 14-16%. If lactate reaches 20 mmol/L, mortality approximates 40% or higher.20 Lactate is an independent marker for mortality, no matter the patient’s hemodynamic status. Lactate greater than 4 mmol/L meets criteria for septic shock, and levels greater than 2 mmol/L are associated with increased mortality and morbidity.1,21-26

What about cryptic shock?

Cryptic shock is defined by sepsis in the patient with normal vital signs. A patient who is hemodynamically stable but with elevated lactate is at increased risk for mortality, as end organ damage occurs soon after lactate production. Thus, lactate serves as an early marker for shock and provides valuable diagnostic information. 9,11,20,21

What to do with the intermediate lactate level…

Lactate > 4 is associated with high mortality, but intermediate levels are as well (2.0-3.9 mmol/L).1,20-26 In fact, levels in this range meets Centers for Medicare and Medicaid Services (CMS) criteria for severe sepsis following SSC guidelines.Importantly, mortality can reach 16.4% for patients in this range, and ¼ of these patients with an intermediate level progress to clinical shock.22 Lactate levels greater than 2 warrant close monitoring and aggressive treatment with IV fluids and antimicrobials. The table below provides recommendations based on lactate level.

Lactate Level CMS Measure Resuscitation Recommendation
< 2 mmol/L None Lactate levels may be negative in over half of patients with sepsis. Clinical gestalt takes precedence over markers.
2-4 mmol/L Severe Sepsis Resuscitation with intravenous fluids, antimicrobials and reassessment of lactate within 60 minutes.
> 4 mmol/L Septic Shock Aggressive resuscitation warranted regardless of vital signs.


Lactate clearance is an important target in sepsis resuscitation. Many target a clearance of 10%, as early lactate clearance is associated with improved outcomes. Arnold et al. found 10% clearance to strongly predict improved outcomes.28 Delayed or no clearance is associated with high mortality, some studies showing 60% mortality rates.28-21 Lactate can be substituted for ScvO2, which requires invasive, specialized equipment.4,28-31


Lactate does not always elevate in sepsis, as 45% of patients with vasopressor-dependent septic shock demonstrate a lactate level of 2.4 mmol/L.32 Hernandez et al. suggested 34% of patients with septic shock did not have elevated lactate, though patients with no lactate elevation had a mortality of 7.7%, while those with lactate elevation 42.9% mortality.33 Lactate should not be used in isolation for assessing presence of shock or as a marker for clinical improvement. Rather, other measures such as mental status, heart rate, urine output, blood pressure, and distal perfusion in combination with lactate is advised.5-7,11



A great deal of literature has evaluated procalcitonin, a calcitonin propeptide produced by the thyroid, GI tract, and lungs with bacterial infection. This biomarker is released in the setting of toxins and proinflammatory mediators, while viral infections inhibit PCT through interferon-gamma production. These levels increase by 3 hours and peak at 6-22 hours, and with infection resolution, levels fall by 50% per day.5-7,34-40 This biomarker can be specific for bacterial infection, decreases with infection control, and is not impaired in the setting of immunosuppressive states (such as steroid use or neutropenia). However, other states including surgery, paraneoplastic states, autoimmune diseases, prolonged shock states, chronic parasitic diseases (such as malaria), certain immunomodulatory medications, and major trauma can increase PCT levels.34-37

Antibiotic Stewardship

Most of the literature evaluating PCT has been published in ICU studies for lower respiratory tract infections (LRTI) and sepsis. The literature suggests algorithms guided by PCT may be able to reduce antibiotic exposure and treatment cost, though with little to no effect on outcomes.37-49

In COPD and bronchitis, it can be difficult to differentiate viral versus bacterial infection. PCT may hold promise in assisting in this differentiation. The ProResp trial randomized patients to two arms, one guided by PCT and the other not.40 If PCT levels were greater than 0.25 mcg/L, antibiotics were given. Ultimately, the group based on PCT demonstrated less antibiotic use (44% in the PCT group, versus 83%), but no difference in length of stay or mortality.40 The ProHOSP trial was a similar trial with the same cutoff. This trial found similar results to the ProResp trial.41


PCT may be useful in sepsis diagnosis, but ultimately, the clinical context and picture must be considered.43-47 Source of infection, illness severity, and likelihood of bacterial infection should take precedence over a lab marker such as PCT, which may not return while the patient is in the ED. If concerned for sepsis, antimicrobials and resuscitation should be started.

 PCT can identify culture positive sepsis and may help in prognostication. Bacterial load may also correlate with level of PCT.34-47 PCT levels of < 0.25 mcg/L indicate that bacterial infection is unlikely, with levels greater than 0.25-0.50 mcg/L indicating bacterial source.38,45-49 However, sensitivity in one meta-analysis was 77%, with specificity of 79%.45

The PRORATA trial evaluated ICU patients admitted with sepsis.48 In this trial, antibiotic use was guided by PCT levels of 0.5 mcg/L. Similar to the prior studies discussed, decreased antibiotic use was found, but the all-important patient mortality benefit was not found. This level of 0.5 mcg/L was recommended as the cutoff for bacterial sepsis diagnosis in a 2015 meta-analysis.49  The following table depicts the PCT levels used in two key studies.

ProHOSP and PRORATA trial PCT Use41,48

Antibiotic Use PCT Level
< 0.1 mcg/L 0.1-0.25 mcg/L 0.25-0.5mcg/L 0.5-1mcg/L > 1.0 mcg/L
ProHOSP antibiotic use (respiratory infection only) No No Yes Yes Yes
PRORATA antibiotic use (sepsis patients in ICU) No No No Yes Yes

Ultimately, PCT should not influence provider decision to diagnose, resuscitate, and manage patients with criteria for sepsis.50,51 This lab may assist ICU providers, specifically when to discontinue antimicrobial therapy. Levels of 0.5 mcg/L strongly suggest bacterial sepsis. Providers in the ICU may be able to trend PCT levels in regards to decision of when to discontinue antimicrobials.  If the clinical picture suggests bacterial source, severe local infection (osteomyelitis, endocarditis, etc.), patient hemodynamic instability, PCT greater than 0.5 mcg/L, or no change in PCT level while on therapy, antimicrobial therapy should continue.37-49


Yep, that’s right, troponin. Troponin is most commonly used to diagnose acute MI, with the AHA stating elevation above the 99th percentile in healthy population meets criteria for ACS.50,51 Troponin can also be used to risk stratify patients entered into the HEART pathway, and high sensitivity troponin can increase sensitivity.50-54 Cardiac troponin consists of two forms: I and T (these are regulatory proteins). Injury of cardiac tissue results in these proteins entering the bloodstream. However, troponin can elevate in multiple settings, shown below.55-59

Cardiac Causes Noncardiac Causes
Acute and Chronic Heart Failure

Acute Inflammatory Myocarditis Endocarditis/Pericarditis

Aortic Dissection

Aortic Valve Disease

Apical Ballooning Syndrome

Bradyarrhythmia, Heart Block

Intervention (endomyocardial biopsy, surgery)


Direct Myocardial Trauma

Hypertrophic Cardiomyopathy


Acute Noncardiac Critical Illness

Acute Pulmonary Edema

Acute PE

Cardiotoxic Drugs

Stroke, Subarachnoid hemorrhage

Chronic Obstructive Pulmonary Disease

Chronic renal failure

Extensive Burns

Infiltrative Disease (amyloidosis)

Rhabdomyolysis with Myocyte Necrosis


Severe Pulmonary Hypertension

Strenuous Exercise/Extreme Exertion

Risk Stratification

Troponin elevation is associated in worse patient outcomes, particularly mortality, as well as increased length of stay. In sepsis, anywhere from 36-85% of patients may demonstrate troponin elevation. 58-68  This elevation is associated with septic shock and mortality, with almost two times the risk of death.58-64,69 Troponin elevation may be due to several factors including demand ischemia, direct myocardial endotoxin damage, cytokine and oxygen free radical damage, and poor cardiac oxygen supply due to microcirculatory dysfunction. 57,60,61,63,65,69 LV diastolic and RV systolic dysfunction are also associated with increased troponin and mortality.64

Troponin elevation in sepsis allows for prognostication and predicts a patient who is sicker. Resuscitation is essential with elevated troponin in sepsis. However, troponin’s role in resuscitation, the assay used, and the cut-off level need to be determined. If an elevation occurs, an ECG should be obtained, along with bedside echo to evaluate for wall motion abnormalities. Sepsis cardiomyopathy can cause diffuse hypokinesis, but focal wall abnormalities require emergent cardiology consultation.56-61


Novel Biomarkers

Sepsis has a complex pathophysiology, which results in a multitude of biomarkers released. These biomarkers are currently under study, and we will discuss several here.5-8

Endothelial Markers

Sepsis results in endothelial changes, associated with modifications in hemostatic balance, change in microcirculation, leukocyte trafficking, vascular permeability, and inflammation.

Measuring this endothelial dysfunction may allow earlier diagnosis of sepsis, as well as prognostication. These include vascular cell adhesion molecule (VCAM-1), soluble intercellular adhesion molecule (ICAM-1), sE-selectin, plasminogen activator inhibitor (PAI-1), and soluble fms-like tyrosine kinase (sFlt-1).5-8,70-73

Proadrenomedullin (ProADM)

This is a precursor for adrenomedullin, a calcitonin peptide. It likely functions in a similar fashion as PCT in the setting of acute cytokine release with bacterial infection. This peptide works as a vasodilator, though it has immune modulating and metabolic effects as well, and it is elevated in renal failure, heart disease, and cancer. ProADM may be able to risk stratify patients with sepsis and pneumonia into different categories based on level.73-79

One study evaluated an algorithm utilizing CURB-65 and ProADM levels.79 CURB-65 is a validated prognostic score for community-acquired pneumonia that consists of BUN > 19 mg/dL (>7 mmol/L), respiratory rate > 30, systolic blood pressure < 90 mm Hg or diastolic blood pressure  < 60 mm Hg, and age > 65 years.80 The algorithm combining CURB-65 and ProADM did not change patient outcome, though it did decrease patient length of stay.79 This marker could assist in prognostication and early discharge, but further study in the ED is needed.

Acute-Phase Reactants

Cytokines are released in response to inflammation, especially sepsis. There are multiple markers including IL-6, IL-8, IL-10, sTREM01, suPAR, CD-64 index, Lipopolysaccharide-binding protein (LBP), ICAM-1, and pentraxins. The greater the elevation in these markers, the worse the prognosis. However, these require further study before regular use can be recommended.8,81

Cardiac Biomarkers

Commonly utilized for heart failure and coronary disease, NT-proBNP and BNP may be associated with worse outcomes in sepsis. Higher levels can predict longer hospital stay and mortality. Obtaining these biomarkers may help predict cardiac dysfunction in sepsis and the need for inotropic medications, though these require further study.67,82-86 Providers must remember that NT-proBNP and BNP lack specificity, as valvular heart disease, Afib, PE, COPD, and hyperthyroidism can elevated these markers, while obesity may decrease levels. 81-85


Key Points:

  • Biomarkers cannot replace the bedside clinician, but they may assist clinical decision making, risk stratification, and prognostication. Lactate has the best evidence in sepsis.
  • Lactate is useful for assessing severity, screening, and resuscitation. However, it is not always elevated in sepsis. Venous POC levels are recommended.
  • Procalcitonin is a marker of bacterial versus viral It is not associated with mortality benefit, but may reduce antibiotic usage. PCT requires further study in the ED.
  • Troponin can be elevated in many conditions and is associated with worse prognosis in sepsis. Sepsis cardiomyopathy is more common than many providers realize.
  • Biomarkers on the horizon include endothelial activators, acute-phase reactants, BNP/NT-proBNP, and proadrenomedullin.


References/Further Reading

  1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013;39:165–228.
  2. Winters BD, Eberlein M, Leung J, Needham DM, Pronovost PJ, Sevransky JE.
Long-term mortality and quality of life in sepsis: a systematic review. Crit Care Med 2010;38:1276–1283.
  3. Strehlow MC, Emond SD, Shapiro NI, et al. National study of emergency department visits for sepsis, 1992 to 2001. Ann Emerg Med 2006;48:326–31.
  4. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368.
  5. Clerico A and Plebani M. Biomarkers for sepsis: an unfinished journey. Clin Chem Lab Med 2013; 51(6): 1135–1138.
  6. Rivers EP, Jaehne AK, Nguyen HB, Papamatheakis DG, Singer D, Yang JJ, Brown S, Klausner H. Early biomarker activity in severe sepsis and septic shock and a contemporary review of immunotherapy trials: not a time to give up, but to give it earlier. Shock 2013 Feb;39(2):127-37.
  7. Schuetz P, Aujesky D, Mueller C, and Mueller B. Biomarker-guided personalised emergency medicine for all – hope for another hype? Swiss Med Wkly 2015;145:w14079.
  8. Di Somma S, Magrini L, Travaglino F, Lalle I, Fiotti N, Cervellin G, et al. Opinion paper on innovative approach of biomarkers for infectious diseases and sepsis management in the emergency department. Clin Chem Lab Med 2013;51:1167–75.
  9. Jones AE. Lactate Clearance for Assessing Response to Resuscitation in Severe Sepsis. Acad Emerg Med 2013 August;20(8): 844–847.
  10. Marik PE, Bellomo R. Lactate clearance as a target of therapy in sepsis: A flawed paradigm. OA Critical Care 2013 Mar 01;1(1):3.
  11. Puskarich MA. Emergency management of severe sepsis and septic shock. Curr Opin Crit Care 2012 Aug;18(4):295-300.
  12. Gibot S. On the origins of lactate during sepsis. Crit Care 2012 Sep 10;16(5):151.
  13. Anderson LW, Mackenhauer J, Roberts JC, Berg KM, Cocchi MN, Donnino MW. Etiology and therapeutic approach to elevated lactate. Mayo Clin Proc 2013 Oct; 88(10): 1127–1140.
  14. Shapiro NI, Howell MD, Talmor D, et al. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med 2005; 45:524–8.
  15. Trzeciak S, Dellinger R, Chansky ME, et al. Serum lactate as a predictor of mortality in patients with infection. Intensive Care Med 2007; 33:970–7.
  16. Singer AJ, Taylor M, Domingo A, Ghazipura S, Khorasonchi A, Thode HC Jr, Shapiro NI. Diagnostic characteristics of a clinical screening tool in combination with measuring bedside lactate level in emergency department patients with suspected sepsis. Acad Emerg Med 2014 Aug;21(8):853-7.
  17. Jones AE, Leonard MM, Hernandez-Nino J, and Kline JA. Determination of the Effect of In Vitro Time, Temperature, and Tourniquet Use on Whole Blood Venous Point-of-care Lactate Concentrations. Acad Emerg Med 2007;14:587–591.
  18. Adams BD, Bonzani TA, Hunter CJ. The anion gap does not accurately screen for lactic acidosis in emergency department patients. Emerg Med J 2006;23:179-82.
  19. Iberti TJ, Leibowitz AB, Papadakos PJ, Fischer EP. Low sensitivity of the anion gap as a screen to detect hyperlactatemia in critically ill patients. Crit Care Med 1990;18:275-7.
  20. Puskarich MA, Trzeciak S, Shapiro NI, Albers AB, Heffner AC, Kline JA, Jones AE. Whole blood lactate kinetics in patients undergoing quantitative resuscitation for severe sepsis and septic shock. Chest 2013 Jun;143(6):1548-53.
  21. Mikkelsen ME, Miltiades AN, Gaieski DF, Goyal M, Fuchs BD, Shah CV, Bellamy SL, Christie JD. Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Crit Care Med 2009 May;37(5):1670-7.
  22. Puskarich MA, Illich BM, Jones AE. Prognosis of emergency department patients with suspected infection and intermediate lactate levels: a systematic review. J Crit Care 2014;29:334-339.
  23. Nichol AD, Egi M, Pettila V, et al. Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multi-centre study. Crit Care 2010;14:R25.
  24. Cady LD, Jr., Weil MH, Afifi AA, Michaels SF, Liu VY, Shubin H. Quantitation of severity of critical illness with special reference to blood lactate. Crit Care Med 1973;1:75-80.
  25. Mizock BA, Falk JL. Lactic acidosis in critical illness. Crit Care Med 1992;20:80-93.
  26. Bakker J, Gris P, Coffernils M, Kahn R, Vincent JL. Serial blood lactate levels can predict the development of multiple organ failure following septic shock. Am J Surg 1996; 171:221–6.
  27. Nguyen H, Rivers E, Knoblich B, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med 2004; 32:1637–42.
  28. Arnold RC, Shapiro NI, Jones AE, et al. Multi-center study of early lactate clearance as a determinant of survival in patients with presumed sepsis. Shock 2009;32:36–9.
  29. Jansen TC, van Bommel J, Schoonderbeek FJ, et al. Early lactate-guided therapy in intensive care unit patients a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med 2010;182:752–61.
  30. Jones AE, Kline JA. Use of goal-directed therapy for severe sepsis and septic shock in academic emergency departments. Crit Care Med 2005;33:1888–9.
  31. Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA 2010;303:739–46.
  32. Dugas AF, Mackenhauer J, Salciccioli JD, Cocchi MN, Gautam S, Donnino MW. Prevalence and characteristics of nonlactate and lactate expressors in septic shock. J Crit Care 2012 Aug;27(4):344-50.
  33. Hernandez G, Castro R, Romero C, de la Hoz C, Angulo D, Aranguiz I, Larrondo J, Bujes A, Bruhn A. Persistent sepsis-induced hypotension without hyperlactatemia: is it really septic shock? J Crit Care 2011 Aug;26(4):435.e9-14.
  34. Jin M and Khan AI. Procalcitonin: Uses in the Clinical Laboratory for the Diagnosis of Sepsis. Lab Medicine 2010 Mar;41(3):173-177.
  35. Pieralli F, Vannucchi V, Mancini A, Antonielli E, Luise F, et al. Procalcitonin Kinetics in the First 72 Hours Predicts 30- Day Mortality in Severely Ill Septic Patients Admitted to an Intermediate Care Unit. J Clin Med Res 2015;7(9):706-713.
  36. Assicot M, Gendrel D, Garsin H, et al. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993;341:515–518.
  37. Meisner M. Pathobiochemistry and clinical use of procalcitonin. Clin Chim Acta 2002;323:17–29.
  38. Muller F, Christ-Crain M, Bregenzer T, Krause M, Zimmerli W, Mueller B, et al. Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial. Chest 2010;138(1):121–9.
  39. Schuetz P, Suter-Widmer I, Chaudri A, Christ-Crain M, Zimmerli W, Mueller B, et al. Prognostic value of procalcitonin in community-acquired pneumonia. Eur Respir J 2011;37(2):384–92.
  40. Christ-Crain M, Muller B. Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators. Eur Respir J. 2007;30:556–573.
  41. Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, Neidert S, Fricker T, Blum C, Schild U, Regez K, Schoenenberger R, Henzen C, Bregenzer T, Hoess C, Krause M, Bucher HC, Zimmerli W, Mueller B; ProHOSP Study Group. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009 Sep 9;302(10):1059-66.
  42. Schuetz P, Muller B, Christ-Crain M, Stolz D, Tamm M, Bouadma L, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev 2012; 9: CD007498.
  43. Jensen J, et al. Procalcitonin as a Marker of Infection, Sepsis, and Response to Antibiotic Therapy. Crit Care Med 2006:34;2596-2602.
  44. Anand D, Das S, Bhargava S, Srivastava LM, Garg A, Tyagi N, Taneja S, Ray S. Procalcitonin as a rapid diagnostic biomarker to differentiate between culture-negative bacterial sepsis and systemic inflammatory response syndrome: a prospective, observational, cohort study. J Crit Care 2015 Feb;30(1):218.e7-12.
  45. Wacker C, Prkno A, Brunkhorst FM, et al. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis 2013;13:426-435.
  46. Schuetz P, Briel M, Mueller B. Clinical outcomes associated with procalcitonin algorithms to guide antibiotic therapy in respiratory tract infections. JAMA 2013;309(7):717–8.
  47. Freund Y, Delerme S, Goulet H, et al. Serum lactate and procalcitonin measurements in emergency room for the diagnosis and risk-stratification of patients with suspected infection. Biomarkers 2012;17:590-596.
  48. Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, Schortgen F, Lasocki S, Veber B, Dehoux M, Bernard M, Pasquet B, Régnier B, Brun-Buisson C, Chastre J, Wolff M; PRORATA trial group. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010 Feb 6;375(9713):463-74.
  49. Hoeboer SH, Van der Geest PJ, Nieboer D, Groeneveld AB. The diagnostic accuracy of procalcitonin for bacteraemia: a systematic review and meta-analysis. Clin Microbiol Infect. 2015;21:474–481.
  50. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Joint ESC/ACCF/AHA/WHF Task Force for Universal Definition of Myocardial Infarction. Third universal definition of myocardial infarction. J Am Coll Cardiol 2012 Oct 16;60(16):1581-98.
  51. Newby LK, Jesse RL, Babb JD, et al. ACCF 2012 expert consensus document on practical clinical considerations in the interpretation of troponin elevations: a report of the American College of Cardiology Foundation task force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2012;60:2427–63.
  52. Mahler SA, Riley RF, Hiestand BC, Russel GB, Hoekstra JW, Lefebvre CW, et al. The HEART Pathway Randomized Trial Identifying Emergency Department Patients With Acute Chest Pain for Early Discharge. Circ Cardiovasc Qual Outcomes March 2015;8 (2):195 – 203.
  53. Thygesen K, Mair J, Giannitsis E, et al. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J 2012;33:2252–7.
  54. Reichlin T, Hochholzer W, Bassetti S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 2009;361: 858–67.
  55. Kelley, W. E., J. L. Januzzi, and R. H. Christenson. Increases of Cardiac Troponin in Conditions Other than Acute Coronary Syndrome and Heart Failure. Clinical Chemistry 2009;55(12):2098-112. Web.
  56. Korff, S. Differential Diagnosis of Elevated Troponins. Heart 2006;92(7):987-93.
  57. Court O, Kumar A, Parrillo JE, Kumar A. Clinical review: Myocardial depression in sepsis and septic shock. Crit Care 2002;6:500-508.
  58. Hamilton MA, Toner A, Cecconi M. Troponin in critically ill patients. Minerva Anestesiol 2012 Sep;78(9):1039-45.
  59. Patil H, Vaidya O, Bogart D. A review of causes and systemic approach to cardiac troponin elevation. Clin Cardiol 2011 Dec;34(12):723-8.
  60. Bouhemad B, Nicolas-Robin A, Arbelot C, et al: Acute left ventricular dilatation and shock-induced myocardial dysfunction. Crit Care Med 2009; 37:441–447.
  61. Wilhelm J, Hettwer S, Schuermann M, Bagger S, Gerhardt F, Mundt S, Muschik S, Zimmermann J, Amoury M, Ebelt H, Werdan K. Elevated troponin in septic patients in the emergency department: frequency, causes, and prognostic implications.Clin Res Cardiol 2014 Jul;103(7):561-7.
  1. Bessière F, Khenifer S, Dubourg J, Durieu I, Lega JC. Prognostic value of troponins in sepsis: a meta-analysis. Intensive Care Med 2013 Jul;39(7):1181-9.
  2. Sheyin O, Davies O, Duan W, Perez X. The prognostic significance of troponin elevation in patients with sepsis: a meta-analysis. Heart Lung 2015 Jan-Feb;44(1):75-81.
  3. Landesberg G, Jaffe AS, Gilon D, Levin PD, Goodman S, Abu-Baih A, Beeri R, Weissman C, Sprung CL, Landesberg A. Troponin elevation in severe sepsis and septic shock: the role of left ventricular diastolic dysfunction and right ventricular dilatation*. Crit Care Med 2014 Apr;42(4):790-800.
  4. Clemente G, Tuttolomondo A, Colomba D, Pecoraro R, Renda C, Della Corte V, Maida C, Simonetta I, Pinto A. When sepsis affects the heart: A case report and literature review. World J Clin Cases 2015 Aug 16;3(8):743-50.
  5. Klouche K, Pommet S, Amigues L, Bargnoux AS, Dupuy AM, Machado S, Serveaux-Delous M, Morena M, Jonquet O, Cristol JP. Plasma brain natriuretic peptide and troponin levels in severe sepsis and septic shock: relationships with systolic myocardial dysfunction and intensive care unit mortality. J Intensive Care Med 2014 Jul-Aug;29(4):229-37.
  6. Cheng H, Fan WZ, Wang SC, Liu ZH, Zang HL, Wang LZ, Liu HJ, Shen XH, Liang SQ. N-terminal pro-brain natriuretic peptide and cardiac troponin I for the prognostic utility in elderly patients with severe sepsis or septic shock in intensive care unit: A retrospective study. J Crit Care 2015 Jun;30(3):654.e9-14.
  7. Courtney D, Conway R, Kavanagh J, O’Riordan D, Silke B. High-sensitivity troponin as an outcome predictor in acute medical admissions. Postgrad Med J 2014 Jun;90(1064):311-6.
  8. de Groot B, Verdoorn RC, Lameijer J, van der Velden J. High-sensitivity cardiac troponin T is an independent predictor of inhospital mortality in emergency department patients with suspected infection: a prospective observational derivation study. Emerg Med J 2014 Nov;31(11):882-8.
  9. Skibsted S, Jones AE, Puksarich MA, Arnold R, Sherwin R, Trzeciak S, et al. Biomarkers of endothelial cell activation in early sepsis. Shock 2013 May; 39(5): 427–432.
  10. Hack CE, Zeerleder S. The endothelium in sepsis: source of and a target for inflammation. Crit Care Med 2001; 29:S21–7.
  11. Shapiro NI, Schuetz P, Yano K, et al. The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis. Critical Care 2010; 14:R182.
  12. Becker KL, Nylen ES, White JC, Muller B, Snider RH, Jr. Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab 2004;89(4):1512–25.
  13. Elsasser TH, Kahl S. Adrenomedullin has multiple roles in disease stress: development and remission of the inflammatory response. Microsc Res Tech 2002;57(2):120–9.
  14. Struck J, Tao C, Morgenthaler NG, Bergmann A. Identification of an Adrenomedullin precursor fragment in plasma of sepsis patients. Peptides 2004;25(8):1369–72.
  15. Christ-Crain M, Morgenthaler NG, Struck J, Harbarth S, Bergmann A, Muller B. Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study. Crit Care 2005;9(6):R816–24.
  16. Christ-Crain M, Morgenthaler NG, Stolz D, Muller C, Bingisser R, Harbarth S, et al. Pro-adrenomedullin to predict severity and outcome in community-acquired pneumonia [ISRCTN04176397]. Crit Care 2006;10(3):R96.
  17. Schuetz P, Wolbers M, Christ-Crain M, Thomann R, Falconnier C, Widmer I, et al. Prohormones for prediction of adverse medical outcome in community-acquired pneumonia and lower respiratory tract infections. Crit Care 2010;14(3) R106.
  18. Albrich WC, Dusemund F, Ruegger K, Christ-Crain M, Zimmerli W, Bregenzer T, et al. Enhancement of CURB65 score with proadrenomedullin (CURB65–A) for outcome prediction in lower respiratory tract infections: derivation of a clinical algorithm. BMC infectious diseases 2011;11:112.
  19. Lim WS, van der Eerden MM, Laing R, Boersma WG, Karalus N, Town GI, Lewis SA, Macfarlane JT. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 2003 May;58(5):377-82.
  20. Reinhart K, Bauer M, Riedemann NC, Hartog CS. New Approaches to Sepsis: Molecular Diagnostics and Biomarkers. Clin Microbiol Rev October 2012;25(4):609-634.
  21. Castillo JR, Zagler A, Carrillo-Jimenez R, Hennekens CH. Brain natriuretic peptide: a potential marker for mortality in septic shock. Int J Infect Dis 2004;8:271–4.
  22. Turner KL, Moore LJ, Todd SR, Sucher JF, Jones SA, McKinley BA, et al. Identification of cardiac dysfunction in sepsis with B-type 
natriuretic peptide. J Am Coll Surg 2011;213:139–46.
  23. Varpula M, Pulkki K, Karlsson S, Ruokonen E, Pettilä V; FINNSEPSIS Study Group. Predictive value of N-terminal pro-brain natriuretic peptide in severe sepsis and septic shock. Crit Care Med 2007;35:1277–83.
  24. Post F, Weilemann LS, Messow CM, Sinning C, Munzel T. B-type natriuretic peptide as a marker for sepsis-induced myocardial depression in intensive care patients. Crit Care Med Lab Med 2008;46:748–63.
  25. Hur M, Kim H, Lee S, Cristofano F, Magrini L, Marino R, Gori CS, Bongiovanni C, et al. Diagnostic and prognostic utilities of multimarkers approach using procalcitonin, B-type natriuretic peptide, and neutrophil gelatinase-associated lipocalin in critically ill patients with suspected sepsis. BMC Infect Dis 2014 Apr 24;14:224.

The Road to Academic Emergency Medicine

Authors: Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC), Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital), and Jennifer Robertson, MD, MSEd (Assistant Professor, Emory University, Atlanta GA)

Emergency physicians train to be highly proficient in the resuscitation and management of acutely ill patients.  In addition, all emergency medicine (EM) training programs focus on preparing physicians to care for these patients in community practice settings. While most EM graduates go on to practice in community settings, academic EM is an option for interested physicians.

In general, academic EM was established to provide the teaching, research, and leadership goals of the specialty. For current residents and community doctors, specific pathways for practicing academic EM are now available, which allow new graduates to directly enter academic EM from residency or transition from community to academic EM.

The decision to practice academic or community practice can be a difficult one to make, as there are perks and drawbacks in both settings. This post will evaluate the road to academic emergency medicine, the positives and negatives, and provide tips for success. However, before we start, we need to understand the difference between academic and community EM.

What is academic emergency medicine?

An academic emergency medicine practice is defined by its providers spending the majority of their time in resident education/supervision, along with scholarly activity (academic writing, teaching, or research).1-5 This focus came into existence in order to meet the teaching, research, administrative, and educational aspects of emergency medicine. The majority of academic providers are associated with a teaching hospital, and many have time protected for academic pursuits. Over 40% of current residents are interested in pursuing an academic career, but the road to determining whether an academic or community practice is right for you can be difficult.1

Unfortunately, many graduating residents feel ill prepared to begin a career in academics, and program directors agree. A survey of EM residency directors found that only 29% feel their program graduates are prepared for an academic career involving original research.2 Obstacles include insufficient research training and resident difficulty in finding knowledgeable collaborators and mentors.

What is community practice?

Community EM refers to practices based mostly on clinical medicine. In community EM, providers spend the majority of their time on clinical duties (usually shifts), rather than supervising and educating residents. Providers may have other obligations such as administrative tasks, but their primary focus is direct patient care. However, the actual amount of patient care duties will vary within individual departments, hospitals, and even parts of the country. Pay is often based on the number of shifts and relative value units (RVUs) per shift. However, overall pay can be also be affected by partnerships, bonuses based on productivity, patient satisfaction, and quality measures.

 Why academic EM?

Academic medicine seeks to pursue scholarship, expand knowledge, and pass on that knowledge. This is most commonly done through resident education and supervision. Education and scholarly activity are ultimately the goals, though these can take several forms. Academics provides career diversity, expertise development, formation of educational philosophy and techniques, specialty advancement, networking and formation of relationships, and research development. It can allow physicians to influence hospital and institution practices, and provide a bit of control in his or her schedule. Best of all, academic EM gives physicians the chance to affect and improve the care of many patients through resident education and scholarly activity.

There are several negative factors associated with academic EM. You will likely work more hours combined, make less money, work fewer clinical hours, and experience more pressure to be scholarly productive (we will cover this later), as compared to community practice.

We know the decision is difficult.

Residency rotations in both settings can provide glimpses of both types of practice. Hybrid programs are also in existence, and it is never too late to switch from one to the other.

In the meantime, how should a resident prepare for academic EM? Residency is the time to obtain several important skills.

1) The first is the most fundamental and important: clinical competency. Excellence in patient care is fine-tuned during residency. Every patient encounter, lecture, and time spent studying should focus on learning and enhancing clinical evaluation and management.

2) The next skill is teaching and knowledge dissemination. This is primarily learned via supervising junior residents or medical students at the bedside or by mentorship. In addition, lecture-based learning and teaching are also paramount.

3) Research skills are essential, no matter what environment you will practice in. Experience in reviewing the literature, establishing research questions and study designs, data collection/analysis, and presentation of data is important.  This can be difficult to obtain through journal clubs only, and some form of higher education is often beneficial for developing key research skills.

4) Expressing ideas and disseminating your knowledge are important, not only for abstracts, papers, and grants, but for hospital protocols and committees.

5) Administrative skills are helpful for both community and academic settings.

6) As most physicians (especially in EM) know, “people” skills are essential, not only to your clinical practice but also in forming long-lasting relationships and collaborations. Whether you go into academic or community EM, these skills are critical.

7) Finally, developing a personal learning strategy is important for continued clinical development.

Ok, so academic EM sounds like your thing… Now what?

There are several aspects of career planning that will help you find the best fit and succeed in academic EM. Each of the following components summarize key information for not only academic survival, but also for long term success.

Preparing for Academics

  1. The importance of a mentor – Mentorship is a key component of a healthy career. Forming a healthy mentoring relationship leads to academic success and career satisfaction, especially when formal postgraduate training is not completed.15-19 Look for mentors within the department, your institution, other institutions, prior training places, and from regional/national meetings. Mentors assist in setting and achieving goals, providing feedback on performance, building confidence and moral support, helping you get involved in committee work, introducing mentees to leaders in your field, protecting you and your interests, and keeping you on track. Your mentor is your advocate.   When choosing a mentor, there are several considerations. These include ensuring the mentor has a track record in the area of your interest, has available time and interest, possesses a personality that fits, and does not possess conflicts of interest. More than one mentor can be helpful, and mentors outside of EM can provide a different viewpoint for you.
  1. Setting time goals: 1, 3, 5, 10 years – Short and long term goals are necessary for a successful career, as a resident and faculty member. You have probably been setting goals all of your life, and just like before, it is important to possess concrete and obtainable goals. A career plan should be established, with each year broken down into separate goals that work toward achieving the long term goal. Keep in mind these may need to be revised, and these goals should be used as a guide for feedback/evaluation sessions. These goals should be discussed with your mentor, with regular meetings and feedback sessions to keep you on track.
  1. Finding your niche – Even though EM is a broad specialty, the majority of academic leaders are known for expertise in one or several areas of knowledge. This is essential for those forming a career: determine what interests or excites you and what opportunities are available to focus on these interests. Ask yourself what your passion is and what excites you. Another key is to consider what you do not enjoy. When you recognize what you like and dislike, then seek to get involved in your area of interest, with a goal of academic productivity (through research, lectures, or publishing). Research projects should also focus on this. Because of EM’s broad spectrum, some may want to target what’s currently available at their institution. Others may take too much on, spreading themselves too thin. It can be difficult to focus on one or two areas, but do your best to choose what interests you the most.
  1. Keep an academic portfolio and curriculum vitae – As most know, a curriculum vitae (CV) is a necessity. Even though different formats may be used, all contain the same information. Your mentor and senior department leadership can provide valuable assistance in forming and fine-tuning your CV. A personal academic profile or portfolio should also be maintained, as this summarizes your teaching, compiles your awards and evaluations, and should also contain examples of lectures and other academic achievements. Both are vital for academic success and promotion.
  1. Join an EM organization – Several emergency medicine societies are available, and each can provide significant benefits. Organizations include AAEM, ACEP, SAEM, CORD, NAEMSP, and several others. These organizations provide valuable networking and socializing opportunities for residents and faculty of all levels. Many of these organizations also have committees, which provide opportunities to improve nonclinical educational skills, form relationships with physicians with similar interests, and contribute to EM. If you can, attend meetings that allow open attendance. You will gain valuable skills in learning how to manage meetings and conferences by watching those in charge.
  1. Networking – There are several aspects to networking. Joining a committee or task force can be helpful and provide links to other departments and senior leaders. Speaking with everyone in the department, from interns to department chair, can form relationships that last. Everyone in EM has lessons learned or advice they can offer. Ask senior department members for connections or to introduce you to other leaders.
  1. Remember your colleagues and provide assistance to others – An academic physician with goals will develop and advance. As you begin to grow in your career, seek to help and mentor others. You obtained your success with the assistance of others, including your mentor and family, and you need to extend this same courtesy to others around you. Involve others in your projects and educational goals. By seeking the advancement of other EM colleagues, you form friendships and long-lasting relationships. If you switched programs, remember those back home and acknowledge them in your success.

What about postgraduate training?

Postgraduate training can help through providing focus on future work, as well as training in teaching, writing, research, and funding. Unfortunately, medical school and residency often do not prepare physicians for an academic career. Though not mandatory for an academic position, postgraduate training can facilitate academic training, enhance career satisfaction, and increase chances of academic success. This training also assists mentoring relationships and collaborative relationships. Dedicated postgraduate training may be the only means of obtaining truly protected time to develop academic skills. Interestingly, fellowship or postgraduate-trained physicians are more likely to obtain success and career satisfaction if involved in an academic program. This training provides increased job mastery, leading to less stress, greater certainty, and improved vision of career goals. Fellowships include pediatric EM, toxicology, undersea and hyperbaric medicine, sports medicine, ultrasound, palliative care, EMS, critical care, and several others. However, further training does delay maximum salary potential.

If you are considering a fellowship, look at each program’s expected clinical time, training value, access to mentors, research opportunities, and total experience. The vast majority of EM fellowship programs offer complete, valuable experiences. If interested in education, fellowship training necessity is less defined. This fellowship is growing, but many departments offer formal, structured, multiyear educational training opportunities. For more information on fellowships, please see EMRA’s complete guide at:

The nuts and bolts for success in academic EM

What roles are there? Academic EM is comprised of many positions, and each institution and program will vary. Research roles include director, clinical trial director, research advisor, and research assistants’ program director. Educational roles can be residency director, associate residency director, medical student director, medical school leadership (dean), rotating resident director, fellowship director, CME director, hospital committee director, and others. There are also specialty roles such as ultrasound, hyperbaric chamber, chest pain, etc. Administrative roles include chief/chair, EMS director, operations director, pediatric ED director, CQI/Risk management director, and others.

Finding the right program – A program that will provide the environment and tools to help you flourish is important. First, characterize the institution, and evaluate what the program rewards (publications, lectures, clinical throughput). Are you just another cog in a vast machine? What would happen if you leave the program? You should ensure true opportunities to advance clinically and professionally exist in the program. Ultimately, look at what the institution and the program can do for you, rather than what you can do for the institution/program.  

Several program types or models possess different attributes. The egalitarian model treats everyone the same, regardless of specific talents or interests. Faculty work similar numbers of shifts, teach a similar number of lectures, carry similar administrate duties, and are expected to have similar productivity. The specialization model demonstrates a more team-based approach. All faculty work clinically, but the department can modify career development to better match faculty member strengths, weaknesses, interests, and dislikes. Shift numbers can vary based on faculty member roles and productivity.

Promotion and tenure – There are progressive ranks with timelines for academic physicians including assistant professor, associate professor, and full professor. Many are based on specific criteria such as publications, grants, regional/national recognition, teaching portfolios, and clinical productivity. An area of focus or niche can be helpful. This should be discussed with your department/program leadership and mentor. A mark of a strong program is a definitive track for career advancement, so you must inquire about this component of the academic program. Many offer workshops or provide further faculty development, which can significantly improve your advancement.

Research – Research is one of the fundamental means of growth for EM. The research environment physicians experience during residency often shapes future interest in research.1,4  At its core, research involves formulating a question, addressing the question with appropriate study design, collection and interpretation of data, and presenting the results in a peer-reviewed journal. This is often a long process, requiring time, effort, and mentorship for residents. Faculty have several goals when it comes to research: conducting research themselves, educating residents on scientific study, and/or how to conduct a study.

A large number of relevant areas of study are in existence. The majority of academic centers will desire their physicians to be “academically productive,” or obtain clinically relevant publications or grants. Research topics can be clinical, basic science, education, policy, or clinical operations. Mentorship and senior physician assistance to residents and new faculty seeking a research track are essential. Properly forming a research question and designing a protocol can be challenging, and thus, the more experience you can obtain, the better.

Teaching – Education is one of the key factors in an academic position. All physicians teach, whether the audience is nurses, technicians, or other physicians. One major component of an academic program is working with residents. Most programs expect academic clinicians to teach on shift as well as present lectures at conferences several times per year. This aspect is often one of the most fulfilling aspects of academic medicine, as you have the opportunity to affect the growth of future EM physicians. You may also work with students and off-service residents, and your relationship with these learners can have significant impact on their education, patient care, and relationships with the emergency department in their future careers.

Residency provides valuable time for honing educational skills. Some programs have dedicated programs for teaching, while others expect those interested in teaching to pick up the skills on their own. Focusing on shift teaching, presentation skills, and creation of lectures are great places to start for residents and new faculty. In emergency medicine, it can be difficult to work on your teaching skills, as there are so many options for teaching and so many different learners. Many adult learners seek information that will directly and positively impact their future careers. Thus, it is important to focus on how individuals learn and how you can make a difference in their learning experiences.

Teaching involves the ability to observe, question, and review trainee performance in actual patient care settings. When developing your own education techniques, look at the educators around you. New faculty and senior residents should pay close attention to those teachers who demonstrate master education skills. At the same time, strongly consider providers who are working on their own deficiencies. You should seek to recognize and understand these deficiencies so you can avoid them. Recognizing these skills and one’s own shortcomings will allow you to grow as an educator.

Scholarly Activity – One major aspect of an academic career is scholarly activity. In the past this included writing, either book chapters, original research, or review articles. The majority of academic programs still rely on clinical research and formal publication in medical journals. The academic environment is evolving, with several other opportunities. Free Open Access Medical Education (FOAMed) is one of these, with a growth of blogs and podcasts. Many academic physicians have now based their career on this avenue. Other options include ACEP’s Critical Decisions in Emergency Medicine, case reports, images, and specialty organization newsletters. Most programs will ask for at least one lecture per academic year, often grand rounds. However, speaking at regional, national, or international meetings is another means of scholarly productivity.

Once you have a project, seek to present the results in multiple settings and formats. Start with presenting an abstract at a conference, then seek publishing in a peer-reviewed journal. A FOAMed blog publication is also an option. Presenting this further at other functions, such as a grand rounds lecture, offers another avenue.  Publication in this format develops writing skills, develops an area of expertise, and advances your career. Remember, most programs still focus productivity on peer-reviewed publications.

The Literature – Residency programs usually promote some form of literature understanding through several formats: journal clubs, evidence-based medicine projects, and education on clinical shifts. Faculty may lead discussions or projects for literature awareness, aimed at promoting a deeper understanding of EM studies. For faculty, a key component of academics is staying abreast of the current literature, as well as “classic” studies. This can be difficult with all of your other duties and clinical shifts, but this is vital to your own education. There are multiple means of remaining current, from subscriptions to journals (Annals of EM, American Journal of EM, Journal of EM, etc.), podcasts (EM:RAP, EMA, EMCrit), and blogs (ALiEM, emDocs, Core EM, EM Updates, REBEL EM). FOAMed has revolutionized medical learning, and residents and faculty can use FOAMed to remain abreast of new, exciting medical updates.

Goals and Persistence – Specific goals with a timeline are a necessity for success in academic medicine, and they must be written down to solidify their importance. The act of setting the goal with timeline, verbalizing it, and writing it creates a commitment. Remember, academic medicine can be and will be difficult. There will be setbacks, but do not be discouraged. You will have papers and grants rejected. Make changes and keep going.

Collaboration – Finding others interested in your niche or topic can benefit. With our schedules, it can be difficult to frequently meet with your mentor to discuss areas of interest. This is where collaboration can help. Team members can provide skills and perspectives that will improve the quality of projects. Just make sure you set specific goals for the project, with a timeline.

Other Specifics – Determine what percentage of your work week should be clinical and what should be given to the rest of your academic pursuits. You should consider what you want to be doing in 5-10 years. Where do you see yourself? Saying “no” is ok if you have too much on your plate.

I think I know how to succeed, but what can I mess up?

There are many pitfalls in academics. These include not enough protection from other duties (working too many clinical shifts with the expectation for academic productivity), not enough training for an academic career (research focus without training on research question and protocol formation), failure to have a mentor (one of the cornerstones of academic success), failure to form a plan/timeline of goals, lack of balance (which leads to burnout), biting off too much, and not listening to feedback.

Importance of Balance – Maintain balance and block off time for your family and hobbies. Success takes time, and it will not occur overnight. Recent years have seen an emphasis on physician health. This really comes down to balancing many aspects of life including your shifts, academics, community activities, exercise, hobbies, family, religious/spiritual concerns, friends, and future plans. Pushing too hard and too fast with too much will lead to burnout.

The Decision – Residency is a great time to explore academics and community practice. Rotations in both settings can help you determine which practice is the best fit for you. You can always switch settings, or in other words, it is never too late to go from community to academic practice. Work on perfecting your clinical skills and management early, as this is essential to both academic and community medicine.

Thanks for reading. For more, please see the resident section of the CORD website at

Please comment below with other tips or questions!

References/Further Reading

  1. Stern SA, Kim HM, Neacy K, Dronen SC, Mertz M. The impact of environmental factors on emergency medicine resident career choice. Acad Emerg Med. 1999 Apr;6(4):262-70.
  2. Neacy K, Stern SA, Kim HM, Dronen SC. Resident perception of academic skills training and impact on academic career choice. Acad Emerg Med. 2000; 7:1408–15.
  3. Aycock RD, Weizberg M, Hahn B, Weiserbs KF, Ardolic B. A survey of academic emergency medicine department chairs on hiring new attending physicians. J Emerg Med. 2014 Jul;47(1):92-8.
  4. Sanders AB, Fulginiti JV, Witzke DB, Bangs KA. Characteristics influencing career decisions of academic and nonacademic emergency physicians. Ann Emerg Med. 1994;23:81–7
  5. Clinton JE. Educating academic emergency physicians. Acad Emerg Med. 1999;6:260–1.
  6. Stead LG, Sadosty AT, Decker WW. Academic career development for emergency medicine residents: a road map. Acad Emerg Med 2005 May;12(5):412-16.
  7. Hobgood C, Zink B (eds). Emergency Medicine: An Academic Career Guide, ed 2. Lansing, MI: Society for Academic Emergency Medicine; 2000.
  8. Faculty Development Web site. Available at: facdev/fac_dev_handbook/. Accessed Nov 10, 2016.
  9. Cydulka C. Preparing for a career in academics. Emergency Medicine: An Academic Career Guide. Available at: http:// Accessed Sep 18, 2001.
  10. Hall KN, Wakeman MA. Residency-trained emergency physicians: their demographics, practice evolution and attrition from emergency medicine. J Emerg Med. 1999;17(1):7-15.
  11. Reinhart MA, Munger BS, Rund DA. American Board of Emergency Medicine Longitudinal Study of Emergency Physicians. Ann Emerg Med 1999;33(1):22-32.
  12. Kellerman AL. Are you considering an academic career? EMRA. Available at Accessed 04 November 2016.
  13. Pines JM. The young physician in academic emergency medicine: tips for success. AAEM. Available at Accessed 04 November 2016.
  14. Sokolove P, Stern S, Baren J. An academic career: is it right for you? 2008 SAEM Annual Meeting, May 2008. Available at Accessed 04 November 2016.
  15. Taylor JS. Academic Medicine 2001;76:366-372.
  16. Stack SJ, Watson MJ. Enriching the resident-faculty relationship. Ann Emerg Med. 2001; 38:336–8.
  17. Osborn TM, Waeckerle JF, Perina D, Keyes LE. Mentorship: through the looking glass into our future. Ann Emerg Med. 1999; 34:285–9.
  18. Hazzard WR. Mentoring across the professional lifespan in academic geriatrics. J Am Geriatr Soc. 1999; 47:1466–70.
  19. Peluchette JV, Jeanquart S. Professionals’ use of different mentor sources at various career stages: implications for career success. J Soc Psychol. 2000; 140:549–64.
  20. Holmboe ES, Ward DS, Reznick RK, Katsufrakis PJ, Leslie KM, Patel VL, Ray DD, Nelson EA. Faculty development in assessment: the missing link in competency-based medical education. Acad Med. 2011; 86(4):460-7.

A Myth Revisited: Epinephrine for Cardiac Arrest

Author: Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

 You receive a radio call from an EMS unit. They are transporting a 61-year-old male who collapsed approximately 5 minutes ago. He is currently in ventricular fibrillation, and the EMS crew is actively doing compressions. They have obtained IV access, defibrillated the patient once, given 1mg epinephrine IV, and are actively bagging the patient. The patient arrives, and you take over the resuscitation. Your partner cleanly intubates the patient while chest compressions are ongoing. The patient receives another defibrillation, and compressions resume. Should the patient receive more epinephrine? What’s the evidence behind its use?

Sudden cardiac arrest accounts for over 450,000 deaths per year in the U.S., with 15% of total deaths due to arrest.1-4 Close to half are out-of-hospital, with poor survival rate (7-9%).1-5

A prior post evaluated epinephrine use in cardiac arrest. Please see this at: Epinephrine is a staple of the AHA Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Updated guidelines were released in 2015, building on a “Chain of Survival”: recognition and activation of emergency response system, immediate high-quality cardiopulmonary resuscitation (CPR), rapid defibrillation, basic and advanced emergency medical services, and advanced life support and post arrest care including advanced cardiac life support (ACLS) for out-of-hospital cardiac arrest (OHCA).7,8 ACLS is considered the standard of care in cardiac arrest, though some argue a lack of evidence.

For more information on the updated guidelines, see,,,

The Myth: Epinephrine improves patient survival and neurologic outcome in cardiac arrest.

Is this important?

A class IIb recommendation from the AHA states “standard dose epinephrine may be reasonable for patients with cardiac arrest” in the 2015 updates, with doses of 1mg of 1:10,000 epinephrine every 3-5 minutes intravenously.7 Epinephrine has alpha and beta adrenergic effects, which are thought to improve coronary perfusion pressure, though the effect on cerebral perfusion is controversial (and may worsen cerebral perfusion).

The recommendation for epinephrine is based on studies in the 1960s, which found epinephrine given to asphyxiated dogs improved survival.9 The alpha-adrenergic effects improved coronary perfusion in these dogs, with some benefit in survival.

If some is good, is more better? High dose epinephrine was assumed to be better, with several studies finding increased ROSC and survival to hospital admission, but no improvement in survival to hospital discharge or neurologic recovery.10-14 Studies suggest worse survival to hospital discharge and neurologic recovery with higher doses of epinephrine.7,15-20

What about standard dose epinephrine?  Studies suggest improvement in ROSC, but worse neurologic and survival to discharge. Why? The beta agonism provided by epinephrine increases myocardial work, increases tachydysrhythmias, promotes thrombogenesis and platelet activation, and reduces microvascular perfusion (including the brain).7,15

Now down to the nuts and bolts: the evidence on epinephrine…

Table 1 shows the studies on epinephrine. A study in 2011 evaluated over 600 patients with OHCA (one of the few randomized trials).16 Improved likelihood of ROSC, 24% in the epinephrine group versus 8%, with an odds ratio (OR) of 3.4 (95% CI 2.0-5.6) was found. Patients demonstrated no improvement in survival to hospital discharge.16 Ong et al. in 2007 found no difference in survival to discharge, survival to admission, or ROSC with epinephrine versus no epinephrine.17

Nakahara et al. conducted a retrospective study comparing epinephrine versus no epinephrine for patients with ventricular fibrillation, PEA, or asystole.18 Higher overall survival with epinephrine (17.0% vs 13.4%) was found, but not neurologically intact survival.18 Hagihara et al. conducted a prospective non-randomized analysis of over 400,000 patients and found an increase in ROSC with epinephrine (adjusted odds ratio 2.36), but no increase in survival or functional outcome.19 As discussed, ROSC occurred in the epinephrine group at higher rate (18.5% vs. 5.7%), but patients receiving epinephrine had lower survival at one month and worse neurologic outcome.19

One study found those with initially shockable rhythm demonstrated worse outcomes if they receive epinephrine for prehospital ROSC, survival at one month, and neurologic outcome at one month.20 A Swedish study found patients receiving epinephrine experience lower survival, with OR 0.30 (95% CI 0.07-0.82).21

How about BLS compared with ACLS?

ACLS measures include epinephrine, as compared with BLS focusing on optimizing compressions. Stiell et al. in 2004 analyzed 1,400 patients before use of ACLS measures, followed by 4,300 patients after ACLS was implemented.22 Admission rate increased by 3.7% (10.9% to 14.6%), but survival to discharge did not change.  Survivor neurologic status worsened after ACLS implementation (78.3% versus 66.8%).22  Olasveengen et al. evaluated ACLS with and without epinephrine, finding a 40% rate of ROSC in the group receiving epinephrine, versus 25% in the group receiving no epinephrine.23 Survival to discharge and neurologic outcomes were similar, though the epinephrine group had higher hospital admission rates.23  Sanghavi et al. compared BLS and ACLS in an observational cohort study.24 BLS patients had higher survival to hospital discharge (13.1% versus 9.2%), improved survival to 90 days, and better neurologic function.24

Table 1 – Studies evaluating epinephrine16-24

Study Outcome Odds Ratio (95% CI)
Holmberg et al. Survival decrease with epinephrine Survival 0.43 (0.27-.066) for shockable, 0.30 (0.07-0.82) for non-shockable rhythms
Stiell et al. Improved ROSC, no difference in survival to discharge Survival to discharge 1.1 (0.8-1.5)
Ong et al. No difference in ROSC or survival to discharge ROSC 0.9 (0.6-4.5), survival to discharge 1.7 (0.6-4.5)
Olasveengen et al. Improved ROSC, No difference in survival to discharge Survival to discharge 1.15 (0.69-1.91)
Jacobs et al. Improved ROSC, No difference in survival to discharge ROSC 3.4 (2.0-5.6), Survival to discharge 2.2 (0.7-6.3)
Hagihara et al. Improved ROSC, Worse survival and functional outcome ROSC 2.35 (2.22-2.5), Survival 0.46 (0.42-0.51), Functional outcome 0.31-0.32 (0.26-0.38)
Nakahara et al. No difference in neurologic outcome or total survival Neurologic outcome 1.01 (0.78-1.30) for shockable and 1.57 (1.04-2.37) for nonshockable rhythms; Total survival 1.34 (1.12-1.60) for shockable and 1.72 (1.45-2.05) for nonshockable rhythms
Sanghavi et al. No epinephrine associated with improved neurologic outcome, survival to discharge, and total survival Improved neurologic outcome 23.0 (18.6-27.4) for no epinephrine, Survival to discharge 4.0 (2.3-5.7) for no epinephrine, Total survival 2.6 (1.2-4.0) for no epinephrine

The Bottom Line: Epinephrine can increase ROSC, but it does not improve survival to hospital discharge or neurological improvement and may worsen these outcomes.

How does this change practice? Epinephrine is a significant component of the AHA guidelines, despite the controversial literature. A role may exist for epinephrine, though further study is required. Studies suggest three phases (electrical, circulatory, and metabolic) are present in cardiac arrest.25 The electrical phase needs rapid defibrillation and compressions.15,25 The circulatory phase (within 10 minutes of arrest) focuses on perfusion, where epinephrine may improve cardiac perfusion. Epinephrine during the final metabolic phase (greater than 10 minutes after arrest) can impair oxygen utilization, increase oxygen demand and ischemia, cause dysrhythmia, increase clotting, and increase lactate.15,25

The timing and total dose of epinephrine can impact patient outcome.7,15,25-27 A study by Dumas et al. suggests timing of first administration and total epinephrine given impacts survival (with less epinephrine given related to improved outcome).25 This study found that 17% of patients in the group receiving epinephrine demonstrated a good outcome defined by “favorable discharge outcome coded by Cerebral Performance Category,” compared to 63% not receiving epinephrine. However, in this study patients with a shockable rhythm, patients receiving 1mg epinephrine, and patients receiving epinephrine less than 9 minutes after arrest demonstrate the best outcomes, not impacted by the total time of resuscitation. Patients receiving late or multiple doses of epinephrine have decreased neurologic survival.25

Table 2 – Epinephrine Dosing Outcomes25

Treatment Adjusted OR (95% CI)
Time to Epinephrine Dose

< 9 min

10-15 min

16-22 min

> 22 min


0.54 (0.32-0.91)

0.33 (0.20-0.56)

0.23 (0.12-0.43)

0.17 (0.09-0.34)

Total Epinephrine Dose

1 mg

2-5 mg

> 5 mg


0.48 (0.27-0.84)

0.30 (0.20-0.47)

0.23 (0.14-0.37)

Epinephrine within 10 minutes of arrest may provide the most benefit. Koscik et al. found earlier provision of epinephrine improved ROSC, from 21.5% to 48.6% (OR 3.45).26 Nakahara et al. compared early epinephrine in OHCA (within 10 minutes of arrest), finding early epinephrine was associated with survival (OR 1.73, 95% CI 1.46-2.04) and improved neurologic outcome (OR 1.39, 95% CI 1.08-1.78).27 However, there is potential harm with epinephrine within the first two minutes of arrest.27 Anderson et al. compared epinephrine before or after the second defibrillation attempt.28 Patients receiving epinephrine before the second defibrillation demonstrated decreased survival (OR 0.70), decreased functional outcome (OR 0.69), and decreased ROSC (OR 0.71). This study suggests epinephrine within the first two minutes after arrest can be harmful, and they recommend epinephrine should be given after the second defibrillation.27

Some support targeting coronary perfusion pressure (CPP), or the aortic to right atrial pressure gradient during the relaxation phase of CPR. Targeting coronary perfusion pressure is supported by several animal studies.29,30 CPP levels > 15 mm Hg demonstrate greater likelihood of ROSC.31 Epinephrine is most commonly used to maintain CPP levels with compressions. However, this needs further study and requires the use of invasive monitoring.25,31

What improves outcomes?

Components that improve outcomes include witnessed arrest, witnessed by EMS, bystander CPR, shockable rhythm (VF/VT), early defibrillation, minimal interruptions to CPR, automated external AED use, and therapeutic hypothermia in comatose cardiac arrest patients.7,15,32 Optimal chest compressions and early defibrillation if warranted are essential.7 Emergency PCI is recommended for all patients with STEMI and for hemodynamically unstable patients without ST elevation infarction if a cardiovascular lesion is suspected. Targeted temperature management between 32oC and 36oC is acceptable for comatose patients with ROSC.7 The 2015 recommendations for BLS measures are shown below. 7,32

2015 Guideline Recommendations for Compressions
-Perform compressions at rate 100-120 per minute

-Perform compressions at depth of 5-6 cm (at least 2 inches), but not more than 6 cm (2.4 in)

-Rescuers should allow full chest wall recoil and avoid leaning on the chest between compressions

-Rescuers should minimize the frequency and duration of intervals between compressions

-Audiovisual devices and compression depth analyzers can be used to optimize CPR quality

Bottom Line: The most important aspect of care in cardiac arrest is basic life support measures with compressions and early defibrillation.



– 2015 AHA Guidelines state epinephrine is reasonable to give for patients in cardiac arrest.

– Recommendations are based on studies with asphyxiated dogs in the 1960s.

High dose epinephrine is harmful and is not advised.

– Epinephrine can increase ROSC, but it may worsen neurologic outcome and survival upon discharge.

– Epinephrine may provide the greatest benefit if given within 10 minutes of arrest (though it may be harmful if given before 2 minutes).

BLS measures with optimal compressions and early defibrillation are essential!


References / Further Reading

  1. Zheng ZJ, Croft JB, Giles WH, Mensah GA. Sudden cardiac death in the United States, 1989 to 1998. Circulation 2001; 104:2158.
  2. Rea TD, Pearce RM, Raghunathan TE, et al. Incidence of out-of-hospital cardiac arrest. Am J Cardiol 2004; 93:1455.
  3. Centers for Disease Control and Prevention (CDC). State-specific mortality from sudden cardiac death–United States, 1999. MMWR Morb Mortal Wkly Rep 2002; 51:123.
  4. Chugh SS, Jui J, Gunson K, et al. Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community. J Am Coll Cardio 2004;44:1268.
  5. Kuller LH. Sudden death–definition and epidemiologic considerations. Prog Cardiovasc Dis 1980; 23:1.
  6. Gillum RF. Sudden coronary death in the United States: 1980-1985. Circulation 1989; 79:756.
  7. Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132:S444-S464.
  8. Neumar RW, Otto CW, Link MS, et al. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122(Suppl 3):S729-67.
  9. Callaham M. Evidence in support of a back-to-basics approach in out-of-hospital cardiopulmonary resuscitation vs. “advanced treatment.” JAMA Intern Med. 2015;175:205-206.
  10. Stiell IG, Hebert PC, Weitzman BN, et al. High-dose epinephrine in adult cardiac arrest. N Engl J Med. 1992;327:1045-1050.
  11. Brown CG, Martin DR, Pepe PE, et al. A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. The Multicenter High-Dose Epinephrine Study Group. N Engl J Med. 1992;327:1051-1055.
  12. Rivers EP, Wortsman J, Rady MY, et al. The effect of total cumulative epinephrine dose administered during human CPR on hemodynamic, oxygen transport, and utilization variables in the postresuscitation period. Chest. 1994;106:1499-1507.
  13. Behringer W, Kittler H, Sterz F, et al. Cumulative epinephrine dose during cardiopulmonary resuscitation and neurologic outcome. Ann Intern Med. 1998;129:450-456.
  14. Guegniaud PY, Mols P, Goldstein P, et al. A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. N Engl J Med. 1998;339:1595-1601.
  15. Callaway CW. Questioning the use of epinephrine to treat cardiac arrest. JAMA. 2012;307:1198-1199.
  16. Jacobs IG, Finn JC, Jelinek GA, Oxer HF, Thompson PL. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial. Resuscitation. 2011 Sep;82(9):1138-43.
  17. Ong ME, Tan EH, Ng FS, Panchalingham A, Lim SH, Manning PG, et al. Survival outcomes with the introduction of intravenous epinephrine in the management of out-of-hospital cardiac arrest. Ann Emerg Med. 2007 Dec;50(6):635-42.
  18. Nakahara S, Tomio J, Takahashi H, et al. Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study. The BMJ. 2013;347:f6829. doi:10.1136/bmj.f6829.
  19. Hagihara A, Hasegawa M, Abe T, Nagata T, Wakata Y, Miyazaki S. Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest. JAMA. 2012 Mar 21;307(11):1161-8. doi: 10.1001/jama.2012.294.
  20. Goto Y, Maeda T, Goto YN. Effects of prehospital epinephrine during out-of-hospital cardiac arrest with initial non-shockable rhythm: an observational cohort study. Critical Care. 2013;17(5):R188. doi:10.1186/cc12872.
  21. Holmberg M, Holmberg S, Herlitz J. Low chance of survival among patients requiring adrenaline (epinephrine) or intubation after out-of-hospital cardiac arrest in Sweden. Resuscitation. 2002 Jul;54(1):37-45.
  22. Stiell IG, Wells GA, Field B, Spaite DW, Nesbitt LP, De Maio VJ, Nichol G, Cousineau D, Blackburn J, Munkley D, Luinstra-Toohey L, Campeau T, Dagnone E, Lyver M; Ontario Prehospital Advanced Life Support Study Group. Advanced cardiac life support in out-of-hospital cardiac arrest. N Engl J Med. 2004 Aug 12;351(7):647-56.
  23. Olasveengen TM, Sunde K, Brunborg C, Thowsen J, Steen PA, Wik L. Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial. JAMA. 2009 Nov 25;302(20):2222-9.
  24. Sanghavi P, Jena AB, Newhouse JP, Zaslavsky AM. Outcomes After Out-of-Hospital Cardiac Arrest Treated by Basic vs Advanced Life Support. JAMA Intern Med 2015;175(2):196-204.
  25. Dumas F, Bougouin W, Geri G, Lamhaut L, Bougle A, Daviaud F, et al. Is epinephrine during cardiac arrest associated with worse outcomes in resuscitated patients? J Am Coll Cardiol. 2014; 64(22):2360–7.
  26. Koscik C, Pinawin A, McGovern H, Allen D, Media DE, Ferguson T, Hopkins W, Sawyer KN, Boura J, Swor R. Rapid epinephrine administration improves early outcomes in out-of-hospital cardiac arrest. Resuscitation. 2013 Jul;84(7):915-20.
  27. Nakahara S, Tomio J, Nishida M, Morimura N, Ichikawa M, Sakamoto T. Association between timing of epinephrine administration and intact neurologic survival following out-of-hospital cardiac arrest in Japan: a population-based prospective observational study. Acad Emerg Med. 2012 Jul;19(7):782-92.
  28. Andersen LW, Kurth T, Chase M, et al. Early administration of epinephrine (adrenaline) in patients with cardiac arrest with initial shockable rhythm in hospital: propensity score matched analysis. BMJ 2016; 353:i1577.
  29. Friess SH, Sutton RM, French B, et al. Hemodynamic Directed CPR Improves Cerebral Perfusion Pressure and Brain Tissue Oxygenation. Resuscitation. 2014;85(9):1298-1303.
  30. Sutton RM, Friess SH, Naim MY, et al. Patient-centric Blood Pressure–targeted Cardiopulmonary Resuscitation Improves Survival from Cardiac Arrest. American Journal of Respiratory and Critical Care Medicine. 2014;190(11):1255-1262.
  31. Paradis NA, Martin GB, Rivers EP, et al. Coronary Perfusion Pressure and the Return of Spontaneous Circulation in Human Cardiopulmonary Resuscitation. JAMA. 1990;263(8):1106-1113.
  32. Sasson C, Rogers MA, Dahl J, Kellermann AL. Predictors of survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2010 Jan;3(1):63-81.

The Great and Powerful HEART Score: Does it have a weakness?

Authors: Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC), Josh Oliver, MD (EM Resident at SAUSHEC, USA), and Matthew Streitz, MD (EM Chief Resident at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

A 52-year-old male presents with 6 hours of chest pain, radiating to the left shoulder and associated with shortness of breath. He has a history of hypertension.  His vital signs and ECG are normal. His initial troponin is normal. You consider entering him into your center’s chest pain pathway, with repeat troponin in two hours.

Chest pain is common in the ED; for the majority of physicians not a single shift will go by without managing at least one patient with chest pain. Approximately 10% of visits to an ED are due to chest pain.1,2 Fear of myocardial infarction often predominates for both patients and physicians.1,2 However, acute coronary syndrome (ACS) accounts for a minority of these patients. In fact, less than 1% of acute myocardial infarctions (MI) are missed by emergency physicians.3,4 Historically, physicians admitted patients with obvious disease (such as STEMI or non STEMI), while other patients underwent some form of further stress testing, either as an inpatient, outpatient dedicated clinic, or in an observation unit. We now know this further risk stratification in patients with negative biomarkers and unchanged ECG offers little, if any benefit.5,6  Testing can lead to over-diagnosis and over-treatment.

The majority of physicians feel a rate of < 1% or 1-2% is appropriate for missed major cardiovascular adverse event (MACE).4,7 Investigators have sought a tool to consistently and efficiently risk stratify patients to less than 1% risk of MACE.8-14  Patients in this low risk category could potentially be discharged directly from the ED. Prior risk scores or decision aids include the TIMI risk score and GRACE, for example.8-12 These scores were not derived for use in the undifferentiated chest pain patient in the ED, but rather for high risk patients to evaluate for the need for invasive therapy.8-12  They are also complex and difficult to use.

The HEART score and pathway have revolutionized care of chest pain patients in the ED.13-17 The introduction of the HEART score demonstrated ability to stratify a significant percentage of patients as low risk and appropriate for discharge, and the HEART pathway with the addition of repeat troponin further decreases the risk of missed ACS to less than 1%.13-17

Many centers use this pathway. However, are there potential weaknesses when using this score or pathway? This post will evaluate these potential weaknesses. But to look for weaknesses, first let’s evaluate the HEART score and pathway. The initial HEART score is shown below.13,14


As you can see, the HEART score consists of age, risk factors, history, ECG, and troponin. Low risk patients, defined by points 0-3, demonstrate low rate of major cardiovascular adverse event (MACE). The original study evaluating the HEART score spanned three months in the Netherlands, finding one third of patients to be low risk.13  The MACE rate in the low risk group was 2.5%.  Since this initial study, the score has been repeatedly validated using multiple methods, with MACE rate less than 2%.14-16

The HEART pathway can further decrease the miss rate, evaluated by Mahler et al.17 This pathway uses a HEART score of 0-3 and negative troponins. Use of this pathway has repeatedly demonstrated ability to risk stratify a large percentage of patients as low risk appropriate for discharge (some studies 40%), with low rate of MACE (< 1%).17


The HEART pathway has demonstrated its utility, but where can it go wrong?

#1: Risk Factors –

Classically, cardiac risk factors (diabetes, hypertension, smoking, hyperlipidemia, family history) have been used to predict the presence or absence of ACS in chest pain. These risk factors were derived in longitudinal studies and likely play little role in the assessment of the patient in front of you.18,19 Jayes et al. finds that no risk factor increases likelihood of ACS in women, while in men, only diabetes and family history increase likelihood.18 A study by Han et al. finds patients over age 65 years overwhelms any other risk factors for predicting ACS, while in patients less than 40, the number of risk factors contributes to risk of ACS.19

The patient may deny medical problems if they never visit a physician or primary care manager. This would potentially give them 0 points, categorized as low risk, no matter the other factors. The patient may not say they have hypertension, hyperlipidemia, or diabetes, but usually when you see an obese patient with BP of 180/90 and blood glucose level of 188, you know better.

Tip: If the patient is hypertensive or has abnormal serum glucose, assume they have these risk factors and score them appropriately. Remember, obesity is a risk factor in the HEART score, and known cardiac disease, cerebrovascular disease, or prior stroke is 2 points on the risk score.13-17

#2: ECG

Significant ST depressions, nonspecific repolarization abnormalities, and normal define the specific categories on the score. Just like above, dynamic ECG changes with no other points on the HEART score could provide a score of 2, which theoretically would place the patient in the low risk category. Approximately 8-11% of patients will demonstrate normal initial ECGs, and in patients with STEMI, up to one third will demonstrate findings on ECG by 30 minutes.20,21 Another potential weakness is misinterpretation of the ECG.

Tip: The ECG must be viewed systematically and thoroughly. Obtain an old ECG if at all possible to look for changes. Do not dismiss T wave changes (such as hyperacute T waves or inversions). These T wave changes must be taken seriously, and repeat ECGs are a necessity, as changes may not be present on the initial ECG.

#3: Troponin

An elevated troponin (2 points) with no other points would categorize the patient as low risk on the HEART score. However, troponin elevation should be considered high risk and criteria for admission. The HEART pathway with troponin elevation takes this into account, with positive troponin resulting in admission for the patient.

Tip: Elevated troponin equals admission. The HEART pathway takes this into account.

#4: Age

Patients greater than 65 years receive two points. However, if they receive 0 points in other categories, this results in a score of 2, which is low risk based on scoring. Progressing age has consistently proven to be a risk factor for ACS, and these patients may not present with chest pain.22 Be wary of the patient with dyspnea, nausea/vomiting, and fatigue who is older.22-27 Also be concerned about the younger patient (such as a 35-year-old) with no risk factors and a story strongly suggestive of ACS.

Tip: Older patients warrant caution. Many do not present typically with chest pain, diaphoresis, and vomiting. Dyspnea is more common. The key for older patients is atypical equals typical.22,27

#5: History

The original HEART score study by Six et al. utilized two investigators to classify patient history.13 Literature demonstrates the most predictive factors of ACS include diaphoresis with chest pain, nausea and vomiting, pain radiation to both arms or right shoulder, and exertional pain.23-26 Chest wall tenderness, pleuritic chest pain, sharp/stabbing chest pain, positional chest pain, and reproducible chest pain decrease the likelihood.23-26 Carefully take a history, and evaluate for these factors.

Tip: Though the prior factors (diaphoresis, vomiting, exertional pain, radiation to both arms/right shoulder) increase the likelihood of ACS, up to 1/3 of patients will present with dyspnea, fatigue, or nausea.27,28 Pay close attention to diabetics, older patients, women, and heart failure patients, as these groups can present atypically.22,27  Atypical presentations are associated with increased mortality.

#6: Gestalt

EM physicians go through extensive training, resulting in tremendous clinical experience and gestalt. How does gestalt compare to the HEART score? Mahler et al. in 2013 compared unstructured physician assessment, HEART score, and North American Chest Pain Rule, each with serial troponins (0 and 3 hrs).17 The HEART score classified 20% of patients as low risk (with 99% sensitivity) compared to gestalt categorizing 13.5% of patients as suitable for discharge (98% sensitivity).17 However, many institutions that utilize the HEART pathway incorporate clinical gestalt.

Tip: Your experience evaluating these patients is invaluable.7 If the HEART score says the patient is low risk but your gestalt says something different, discuss this with your admitting team and the patient. Many missed cases of ACS are associated with younger patients with no risk factors but a concerning story for cardiac etiology of their chest pain. The patient likely warrants admission in this setting.

#7: Follow up

Some institutions that utilize the HEART pathway and discharge patients with scores 0-3 attempt to have patients follow up with their primary care physician. Mahler et al.’s HEART pathway study encouraged follow up, but did not mandate it.17 As many know, follow up isn’t always possible. Patients with borderline scores (such as a score of 3), may not be able to see a primary care physician for another visit. However, the AHA/ACC recommend further stratification within 72 hours of discharge, though many are moving from this.29

Tip: Advise your patient to follow up, and document the discussion. Ensure return precautions are provided, and more importantly, that the patient verbalizes and understands these precautions.

 #8: Points 3 or 4

The dividing line for low risk is 3, while a score above 3 is moderate or high.13-17 The line between 3 or 4 points can be gray, dependent on which areas receive points. A history given 1 point may be 2 points based on the assessment of another physician. A study evaluating MACE rate for each number of points on HEART would provide valuable information on the score and pathway.

#9: Research Design

This post will not delve into the design of the HEART score/pathway trials, but several items should be considered. First is pathway adherence in the studies, as some nonadherence was observed. Another component is potential physician disagreement on scoring. Some studies do not list HEART interobserver agreement, while others state that physicians were notified if any disagreement occurred.


How can we improve on the HEART score?

The risk of ACS in patients admitted with chest pain, normal ECG, and negative troponin is close to 0.2%.3 The HEART pathway provides support for discharging patients with scores 0-3. Some have sought means of improving the score. One study modified the score by weighing male gender separately, as well as obtaining serial troponins and ECGs over 2 hours.30 This is known as the HEARTS(3) score. The S(3) correlates to sex, serial 2-hour ECG, and serial 2 hour delta troponin. Investigators also find that history highly suspicious of ACS (+LR 13) is much stronger than 3 or more CAD risk factors or age over 65 (+LR 1.4).30   Serial troponins and serial ECGs may improve miss rates, but most providers obtain serial ECG and troponins in patients with chest pain.

Further areas of study include disposition and medical decision making in patients with scores 4-6, or intermediate risk patients. These patients have approximately 12-16% risk of MACE.13-17 Does stress testing add to this population? The benefits of stress testing are controversial, and further risk stratification with these tests is difficult.

What about the use of coronary CTA in moderate risk patients? If this test demonstrates no disease (or less than 50%), the risk of ACS is very low.31-37 However, the majority of the literature has evaluated the use of CCTA in patients already at low risk for ACS.33-37  Perhaps a pathway using CCTA for patients with scores 4-6 may allow discharge and further risk stratification, but this requires more study.


Summary and Takeaways:

– The risk of ACS in patients with negative biomarkers and normal ECGs approaches 0.2%.

– Prior risk scores, such as TIMI and GRACE, provide little, if any benefit, in risk stratification for ED chest pain patients.

– The HEART score and pathway can risk stratify patients into three separate categories: low (0-3), moderate (4-6), and high score (> 7).

Low risk patients on the HEART pathway demonstrate likelihood of ACS that approaches < 1%, and it is easy to use in the ED.

Risk factors, history, ECG, troponin, follow up, gestalt, patients with points 3 or 4, and research design are areas of potential weakness.

– Further improvement of the HEART pathway at this time is difficult, but in patients at moderate risk, CCTA may hold promise for evaluation of risk. This requires further study.

References/Further Reading

  1. Bhuiya FA, Pitts SR, McCaig LF. Emergency department visits for chest pain and abdominal pain: United States, 1999–2008. NCHS Data Brief. 2010;(43):1–8.
  2. Pope JH, Aufderheide TP, Ruthazer R, et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med. 2000;342(16):1163–1170.
  3. Weinstock MB, Weingart S, Orth F, et al. Risk for clinically relevant adverse cardiac events in patients with chest pain at hospital admission. JAMA Intern Med 2015;175: 1207-1212.
  4. Than M, Herbert M, Flaws D, et al. What is an acceptable risk of major adverse cardiac event in chest pain patients soon after discharge from the Emergency Department? A clinical survey. Int J Cardiol 2013;166:752-754.
  5. Kosowsky JM. Approach to the ED patient with ‘‘low-risk’’ chest pain. Emerg Med Clin North Am 2011;29:721–7.
  6. Lai C, Noeller TP, Schmidt K, King P, Emerman CL. Short-term risk after initial observation for chest pain. J Emerg Med 2003;25: 357–62.
  7. Kline J.A., Johnson C.L., Pollack C.V., et al: Pretest probability assessment derived from attribute matching. BMC Med Inform Decis Mak 2005; 5: pp. 26.
  8. Antman EM, Cohen M, Bernink PM, et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA. 2000;284(7):835–842.
  9. Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low- molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med. 1997;337:447–452.
  10. Eagle KA, Lim MJ, Dabbous OH, et al. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry. JAMA. 2004;291(22):2727–2733.
  11. Lyon R, Morris AC, Caesar D, et al. Chest pain presenting to the Emergency Department – to stratify risk with GRACE or TIMI? Resuscitation. 2007;74(1):90–93.
  12. GRACE Investigators. Rationale and design of the GRACE (Global Registry of Acute Coronary Events) project: a multinational registry of patients hospitalized with acute coronary syndromes. Am Heart J. 2001;141:190–199.
  13. Six AJ, Backus BE, Kelder JC. Chest pain in the emergency room: value of the heart score. Neth Heart J 2008;16:191-6.
  14. Backus BE, Six AJ, Kelder JC, et al. Chest pain in the emergency room. A multicenter validation of the HEART score. Crit Pathw Cardiol 2010;9:164–9.
  15. Backus BE, Six AJ, Kelder JC, Bosschaert MA, Mast EG, Mosterd A, et al. A prospective validation of the HEART score for chest pain patients at the emergency department. Int J Cardiol 2013 Oct 3;168(3):2153-8.
  16. Mahler SA, Hiestand BC, Goff DC Jr, Hoekstra JW, Miller CD. Can the HEART score safely reduce stress testing and cardiac imaging in patients at low risk for major adverse cardiac events? Crit Pathw Cardiol 2011;10:128–133.
  17. Mahler SA, Riley RF, Hiestand BC, Russell GB, Hoekstra JW, Lefebvre CW. The HEART Pathway randomized trial: identifying emergency department patients with acute chest pain for early discharge. Circ Cardiovasc Qual Outcomes 2015 Mar;8(2):195-203.
  18. Jayes RL Jr, Beshansky JR, D’Agostino RB, Selker HP. Do patients’ coronary risk factor reports predict acute cardiac ischemia in the emergency department? A multicenter study. J Clin Epidemiol. 1992 Jun;45(6):621-6.
  19. Hans JH, et al. The role of cardiac risk factor burden in diagnosing acute coronary syndromes in the emergency department setting. Ann Emerg Med 2007;49(2):145.
  20. Welch RD, Zalenski RJ, et al. Prognostic Value of a Normal or Nonspecific Initial Electrocardiogram in Acute Myocardial Infarction. JAMA 2001;286(16):1977-1984.
  21. Riley RF, et al. Diagnostic time course, treatment, and in- hospital outcomes for patients with ST-segment elevation myocardial infarction presenting with nondiagnostic initial electrocardiogram: a report from the American Heart Association Mission: Lifeline program. Am Heart J 2013 Jan;165(1):50-6.
  22. Alexander KP, et al. Acute coronary care in the elderly, part I: Non-ST-segment elevation acute coronary syndromes. Circulation 2007;115:2549-2569.
  23. Body R, Carley S, Wibberley C, McDowell G, Ferguson J, Mackway-Jones K. The value of symptoms and signs in the emergent diagnosis of acute coronary syndromes. Resuscitation. 2010 Mar;81(3):281-6.
  24. Edwards M, Chang AM, Matsuura AC, Green M, Robey JM, Hollander JE. Relationship between pain severity and outcomes in patients presenting with potential acute coronary syndromes. Ann Emerg Med. 2011 Dec;58(6):501-7.
  25. Goodacre S, Locker T, Morris F, Campbell S. How useful are clinical features in the diagnosis of acute, undifferentiated chest pain? Acad Emerg Med. 2002 Mar;9(3):203-8.
  26. Panju AA, Hemmelgarn BR, Guyatt GH, Simel DL. The rational clinical examination. Is this patient having a myocardial infarction? JAMA. 1998 Oct 14;280(14):1256-63.
  27. Brieger D, et al. Acute coronary syndromes without chest pain, an underdiagnosed and undertreated high-risk group. Insights from the Global Registry of Acute Coronary Events. Chest 2004;126(2):461-9.
  28. Dorsh MF, et al. Poor prognosis of patients presenting with symptomatic myocardial infarction but without chest pain. Heart 2001;86(5):494-8.
  29. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;64(24):e139-e228.
  30. Fesmire FM, Martin EJ, Cao Y, Heath GW. Improving risk stratification in patients with chest pain: the Erlanger HEARTS3 score. Am J Emerg Med. 2012 Nov;30(9):1829-37.
  31. Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the Management of Stable Coronary Artery Disease of the European Society of Cardiology. Eur Heart J 2013;34:2949–3003.
  32. Fihn SD, Gardin JM, Abrams J, et al., American College of Cardiology Foundation/American Heart Association Task Force. 2012 ACCF/AHA/ACP/AATS/PCnA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart dis- ease: a report of the American College of Cardiology Foundation/ American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2012;126:e354–471.
  33. Achenbach S. Can coronary computed tomography angiography replace invasive angiography? Yes: it is all about finding the right test for the right person at the right time. Circulation 2015;131: 410–6. discussion 417.
  34. Stefanini GG, Windecker S. Can coronary computed tomography angiography replace invasive angiography? Coronary computed tomography angiography cannot replace invasive angiography. Circulation 2015;131:418–25. discussion 426.
  35. deFilippi CR, Rosanio S, Tocchi M, et al. Randomized comparison of a strategy of predischarge coronary angiography versus exercise testing in low-risk patients in a chest pain unit: in-hospital and long- term outcomes. J Am Coll Cardiol 2001;37:2042–9.
  36. Litt HI, Gatsonis C, Snyder B, et al. CT angiography for safe discharge of patients with possible acute coronary syndromes. N Engl J Med 2012;366:1393–403.
  37. Redberg RF. Coronary CT angiography for acute chest pain. N Engl J Med 2012;367:375–6.

Outpatient PE Management: Controversies, Pearls, and Pitfalls

Authors: Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC, USAF) and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital) // Edited by: Jamie Santistevan, MD (@Jamie_Rae_EMdoc, Admin and Quality Fellow at UW, Madison, WI) 

A 42-year-old female presents with pleuritic chest pain and dyspnea with exertion. Her VS include HR 102, RR 21, O2 sat 98% on RA, and T 98. Her ECG and chest X-ray are normal, as well as laboratory studies including troponin and BNP. You obtain a CTA chest, which demonstrates a right segmental PE. Does this patient require admission? What anticoagulation options do you have?

Pulmonary embolism (PE) is a common disease, with an incidence approaching 56 per 100,000 patients. This increases with age with 500 per 100,000 in patients over 80 years.1-6 Over 100,000 deaths occur annually in the U.S from PE.4-6 Diagnosis of PE has increased with improved technology; however, the mortality of PE has remained similar despite increased diagnosis.7-9 


Increased testing, including D-dimer and CTA, has resulted in more PEs diagnosed.7-9 Instead of reducing morbidity and mortality, physicians may actually be increasing patient risk in an attempt to diagnose PE.11,12 One study demonstrates that PE testing prevents 6 deaths and 24 major PE-related events, while causing 36 deaths and 37 PE-related harms such as renal failure due to contrast, major hemorrhage, and cancer due to radiation from CT.13-15

Strategies have been suggested to decrease this potential patient harm. Risk scores can be used to assist providers in evaluation, in association with D-dimer and imaging.10-12 Another option is the use of risk stratification to determine which patients are appropriate for discharge home with treatment, as opposed to inpatient admission and treatment.10-12

Inpatient Versus Outpatient Management History

Patients with VTE have historically been admitted for treatment and monitoring. Over 90% of EDs admit patients with PE in the U.S., with therapy including heparin and warfarin.10,16-19 The advent of low molecular weight heparins (LMWHs) and fondaparinux made home treatment possible, specifically for DVT.20-22 These medications are safe and efficacious, while not requiring regular monitoring. These attributes make home treatment feasible.

Close to one third of these patients with DVT have an associated PE.23 In Canada, studies in the early 2000’s demonstrated the safety of outpatient treatment for PE, with 50% of patients safely treated at home.20,24,25 In the U.S. this is not common, as well as other parts of the world.26-28 Even in the era of novel oral anticoagulants, over 98% of patients with PE are admitted for inpatient treatment.29 Despite this trend in the U.S., studies suggest close to 50% of patients are appropriate for outpatient management, specifically patients categorized as low risk for adverse outcome.10,30 The recently updated American College of Chest Physicians 2016 guidelines provide a Grade 2B recommendation for outpatient management for patients with low-risk PE.10

Outpatient Treatment Barriers

The majority of centers in the U.S. admit patients with PE. One issue is the uncertainty in identifying patients at low risk for adverse outcome appropriate for discharge.29,31 Many are not comfortable with the use of criteria for outpatient therapy.32-37

Outpatient Treatment Benefits

Several benefits exist for providing outpatient care of PE. Potential improvements in quality of life, social function, and physical activity are possible with outpatient care.20,29,31,36 Outpatient therapy is associated with decreased length of stay and reduction in overall cost. Estimates demonstrate a potential savings of $7 million per year.37,38 Not only can outpatient treatment reduce cost, but it is safe with proper risk stratification.


The controversy surrounding outpatient PE therapy centers on three questions:

  • Is outpatient treatment for PE inferior to inpatient treatment?
  • Is the risk of harm greater with outpatient versus inpatient therapy?
  • Finally, what tools are present for patient risk stratification?

 Outpatient versus Inpatient Therapy

The literature suggests outpatient therapy is not inferior to inpatient therapy. A study in 2011 finds that of 344 patients with acute PE, one patient in the outpatient group versus no patients in the inpatient group experienced recurrent VTE, statistically noninferior.39 One patient out of 173 outpatients in this study developed recurrent VTE, with one death in the inpatient group and outpatient group.39 A study by Fang et al. from 2015 conducted an evaluation of low risk PE patients based on the PE Severity Index (PESI), with 494 of 5927 patients treated as outpatient. Investigators find no deaths within 30 days, with two deaths at 90 days with outpatient therapy.40 However, a Cochrane review suggests the current literature is not sufficient to assess efficacy and safety of outpatient versus inpatient therapy for PE due to small sample sizes.41 Though a higher evidence level would be helpful, current literature suggests outpatient management is safe, feasible, and efficacious for a significant percentage of patients with acute PE.

Outpatient Therapy Outcomes

Literature does suggest safety with outpatient treatment. Two studies demonstrate that patients with non-massive PE, hemodynamic stability, and no oxygen requirement treated with LMWH and warfarin have extremely low risk of adverse outcome, with no patients dying of PE at 3 months, and 13 of nearly 600 patients experiencing recurrent VTE.25,42 A study by Kovacs et al. evaluated 639 patients, of which 314 were low risk and managed as outpatient. Less than 1% of patients experience hemorrhage (3 patients) or recurrent VTE (3 patients) in this cohort.25 Erkens et al. investigated 473 patients, with 55% treated as outpatient.42 No deaths due to PE occur in this cohort, with 0.4% recurrent VTE rate in the outpatient group within two weeks. No bleeding occurred at two weeks.42

The American College of Chest Physicians (ACCP) and European Society of Cardiology (ESC) indicate that risk tools may be used to identify patients at low risk for adverse event and early mortality.10,34 Patients at low risk may be discharged home for treatment.

Zondag et al. finds recurrent VTE, major bleeding, and all-cause mortality to not be significantly different between acute PE patients treated as outpatient versus inpatient.43 Aujesky et al. finds that treatment of acute PE patients at low risk using the PESI score, defined by classes 1 or 2, demonstrates efficacy and safety.39 This study did exclude patients with active bleeding, high risk for bleeding, poor social situation, renal failure, hypoxemia, pregnancy, and extreme obesity. Per these results, VTE, bleeding, and overall mortality rates are noninferior at 14 and 90 days at follow-up.39 Vinson et al. conducted a systematic review of studies evaluating patients with acute PE and PESI 1 or 2 treated initially with enoxaparin and oral warfarin.44 Those deemed appropriate for outpatient treatment do not demonstrate significant adverse event rate difference with the admitted group.44

A recent study released in 2015 evaluated the use of rivaroxaban 15 mg by mouth twice daily for 21 days, followed by 20 mg once per day. Investigators used modified Hestia Exclusion Criteria, discussed later, to identify patients at low risk for adverse outcome.45 Results suggest this option is safe. In this cohort of 106 patients discharged with VTE, 28% have PE%, 67% have DVT, and 5% have combined DVT and PE. No patients experience new VTE, while three patients experience recurrent VTE after treatment discontinuation.45

Risk Stratification and Low-Risk Patients

Studies demonstrate outpatient PE treatment is feasible and safe for patients at low risk for PE mortality. ACCP guidelines recommend outpatient treatment for low-risk patients with adequate social situation.10 However, there is no consensus on which rule/score to use. Investigators have sought a rule or score that can identify patients at low risk for PE-related mortality. These include the Pulmonary Embolism Severity Index (PESI), original and simplified versions, Geneva Prognostic Score (GPS), Global Registry of Acute Coronary Events (GRACE), Hestia Criteria, and Aujesky score.

PESI was originally developed to estimate mortality at 30 days in patients with acute PE utilizing eleven factors.46,47 Studies have evaluated PESI to identify patients with PE who are appropriate for discharge if low risk. Sensitivity approaches 89%, with specificity 49%, positive predictive value (PPV) 11%, and negative predictive value (NPV) 98%.46-49 Of patients with suspected PE, approximately 45% of patients meet low risk criteria.46-49

Simplified PESI uses 7 factors from the original PESI. Any item positive in the index places the patient at higher risk for adverse event.50,51 The simplified index possesses sensitivity 96.1%, specificity 38%, PPV 11%, and NPV 99%. The simplified PESI demonstrates similar prognostic accuracy, as well as similar NPV and PPV.50,51 However, the simplified PESI is easier to use and does not require calculation, which reduces complexity, as well as placing 35% of patients at low-risk. Over 25,000 patients have undergone analysis with this rule.50,51 A post-hoc analysis of the EINSTEIN PE study released in 2015 finds that patients with sPESI of < 1 treated with rivaroxaban as an outpatient to have low incidence of major adverse events within 30 days. Scores of 0 demonstrate a recurrent VTE rate of 0.8%, while scores of 1 have a recurrent VTE rate of 1.0%.52 All-cause mortality is also low. Patients with scores > 2 possess greater rates of recurrent VTE (4.3%), all-cause mortality (10.2%), PE-related mortality (1.7%), and major bleeding (4.0%).50-52

Original and Simplified Pulmonary Embolism Severity Index (PESI)
Variable Score

     Original PESI                 Simplified PESI


Male sex

History of cancer

History of heart failure*

History of chronic lung disease*

Pulse > 110 beats/min

Systolic blood pressure < 100 mm Hg

Respiratory rate > 30 breaths/min

Temperature < 36oC

Altered mental status

Oxygenation saturation < 90%

Age in years











Age > 80 = 1











PESI Score

Score         Class       30 day mortality

< 65             I               0-1.6%

66-85           II             1.7%-3.5%

86-105         III             3.2%-7.1%

106-125       IV             4.0%-11.4%

> 125           V               10.0%-24.5%

SPESI – > 1 point warrants consideration of inpatient therapy


*The combination of heart failure and chronic lung disease defines cardiopulmonary disease

The Hestia Criteria utilizes eleven clinical markers, shown below. Any positive criteria warrants consideration of treatment as inpatient. If none are present, the patient may be treated as an outpatient. A study by Zondag et al. including 496 patients finds a sensitivity of 82% (95% CI 0.52-0.95) and specificity of 56% (95% CI 0.52-0.61).43 A three month follow up period reveals approximately 1% mortality rate, though none from PE. Recurrent VTE occurred in 2.0% of the outpatient treatment group. Major bleeding occurs in less than 1% of patients.43,45 Close to 55% of patients are categorized as low risk based on these criteria.43,45 A 2015 study by Beam et al. utilized the Hestia Criteria to risk stratify patients and finds those at low risk to have no recurrent VTE or major bleeding while on anticoagulation.43,45 The Hestia Criteria can be quickly used at the bedside to risk stratify patients.

Hestia Criteria
1. Hemodynamically unstable?

2. Thrombolysis or embolectomy necessary?

3. Active bleeding or high risk of bleeding?

4. Oxygen supply to maintain oxygen > 90% > 24 hr?

5. Pulmonary embolism diagnosed during anticoagulant treatment?

6. Intravenous pain medication > 24 hr?

7. Medical or social reason for treatment in hospital > 24 hr?

8. Creatinine clearance less than 30 mL/min?

9. Severe liver impairment?

10. Pregnant?

11. Documented history of heparin-induced thrombocytopenia?

-If any of the above are answered “yes,” the patient should NOT be treated as outpatient

-An answer of “no” to all of the above meets criteria for outpatient therapy

The Geneva Prognostic Score (GPS) is comprised of six variables including clinical, laboratory, and ultrasound findings.53 Low risk patients demonstrate a rate of adverse outcomes of 2.2%-5%, with sensitivity ranging from 40% to 85% and NPV of 95% to 98%.53 Studies demonstrate that use of this score can place 76% to 88% of patients as low risk.53,54 Validations of this score have not yielded similar results, with high mortality and lower sensitivity.54

Geneva Prognostic Score – Revised and Simplified Versions
Variable Score

           Revised                     Simplified

Age > 65 yr

Previous PE or DVT

Surgery or fracture within 1 month

Active cancer

Unilateral leg pain


Heart rate (bpm)


> 95

Pain on lower limb venous palpation and unilateral edema

Low probability

Intermediate probability

High probability













> 11













> 5

The European Society of Cardiology (ESC) guidelines on the diagnosis and management of acute PE stratify patients into several levels of risk for death.34 Per ESC guidelines, this stratification scheme should only be used in patients with suspected PE. Low risk is defined by negative RV strain on biomarkers and imaging. Sensitivity approaches 88%, with 23% to 36% of patients meeting low-risk criteria.34,54

PE-related early mortality Risk Markers

Clinical                 RV                     Cardiac

(shock)           dysfunction               Injury

Potential treatment


High (>15%) + + + Thrombolysis






+ + Admission





Early discharge or home treatment
Principal markers of risk stratification:

1. Clinical Markers – Shock, hypotension

2. Markers of RV dysfunction – RV dilatation, hypokinesis or pressure overload on US, RV dilatation on spiral computed tomography, BNP or NT-proBNP elevation, elevated right heart pressure on right heart catheterization

3. Markers of myocardial injury – Positive cardiac troponin T or I

The Global Registry of Acute Coronary Events (GRACE) has a high diagnostic ability for adverse outcomes in acute coronary syndrome (ACS); however, investigators have sought to use this score for PE risk stratification.55 The components of this score can be complex ( Sensitivities approach 99%, with specificities of 27%. Only 22% of patients meet low risk criteria based on this score.54,55 This score can be difficult to use in the ED, and evidence support is low.

The Aujesky score, first published in 2006, takes into account factors similar to PESI and sPESI.46 These include 10 patient factors and clinical variables. Use of this rule shows 30-day mortality rates for low risk patients 0.6%, 1.5%, and 0% in the derivation, internal validation, and external validation studies, respectively.46,47,48,58 Sensitivities approach 99%; however, upon pooled analysis, only 22% of patients meet low risk criteria.

How do the scores compare?

A 2015 meta-analysis identifies several clinical prediction rules with sensitivities near 90% including sPESI, PESI, and European Society of Cardiology (ESC).54 PESI, sPESI, ESC, and Geneva rules demonstrate high quality of evidence, but the scores with lowest study bias include PESI, sPESI, and Geneva. This meta-analysis does not recommend use of the Geneva score due to its low sensitivity of approximately 40%, and the PESI tool is difficult to score due to use of 11 variables. However, sPESI and ESC rules display potential qualities for use in PE risk stratification. These rules also identify approximately 45% as low risk of early all-cause mortality, but specificities only approach 50%.54


Clinical Prediction Rule Sensitivity (95% CI) Specificity

(95% CI)

% Low Risk (95% CI)
PESI 0.89 (0.87-0.90) 0.49 (0.44-0.53) 45 (42-49)
sPESI 0.92 (0.89-0.94) 0.38 (0.32-0.44) 35 (31-39)
Geneva 0.41 (0.29-0.55) 0.85 (0.81-0.88) 82 (76-88)
ESC 0.88 (0.77-0.94) 0.38 (0.28-0.49) 36 (26-46)
Hestia 0.82 (0.52-0.95) 0.56 (0.52-0.61) 55 (51-60)
GRACE 0.99 (0.89-1.00) 0.27 (0.21-0.34) 22 (17-28)
Aujesky 0.97 (0.95-0.99) 0.24 (0.19-0.31) 22 (19-25)

Combining Prediction Rules with Biomarkers and Imaging

Patients with acute PE are often assessed with multiple biomarkers including BNP and troponin, and elevations in these markers are associated with increased risk of adverse event. NT-proBNP elevation above 600 pg/mL and right ventricular dysfunction on echocardiogram assist risk stratification with PESI.57 Jimenez et al. finds combining sPESI with negative BNP possesses a NPV for adverse event of over 99%.58 A study by Singanayagam et al. suggests the combination of troponin and PESI to improve the predictive value of 30 day mortality.59 Sanchez et al. demonstrates the addition of RV dysfunction on US in association with PESI can predict adverse outcome.60 Per the ESC, any biomarker elevation or findings of RV dysfunction on imaging places the patient in the intermediate risk category, unsuitable for outpatient therapy per the ESC.34 However, other studies demonstrate the addition of biomarkers to clinical scores may not improve risk stratification. Moores et al. in 2013 finds that negative troponin I with low-risk PESI does not improve NPV ability.61 Zondag et al. in evaluation of the Hestia criteria, which does not take into account biomarkers or imaging, finds it to have greater predictive value of adverse clinical outcome when compared to ESC criteria (the ESC criteria does use biomarkers and echocardiogram).43 Literature may conflict, but risk stratification in association with negative biomarkers may place the patient at low risk for adverse event.

Novel Oral Anticoagulants (NOAC)

The novel, target-specific non-vitamin K antagonists (VKA) oral anticoagulants have improved outpatient therapy.10,62 ACCP guidelines support the use of these agents for three months.10 The EINSTEIN PE Trial randomized patients to rivaroxaban 15 mg two times daily for three weeks followed by 20 mg once per day, versus standard therapy with enoxaparin followed by adjusted dose VKA therapy.63 The rivaroxaban group demonstrates a 2.1% rate of recurrent VTE, versus standard therapy 1.8%. Per study results, major bleeding occurs in 1.1% of the rivaroxaban group and 2.2% of the standard therapy group. The results suggest fixed-dose rivaroxaban is non-inferior to standard therapy with enoxaparin and oral VKA.63 The AMPLIFY study finds apixaban to be noninferior to standard therapy, with lower rates of bleeding in the apixaban group, 4.7% versus 9.7%.64 All-cause mortality and recurrent VTE are similar based on this study.64 A systematic review and meta-analysis finds similar rates of recurrent VTE, death, and major bleeding between warfarin and NOAC treatment.65

The Factor Xa antagonists, rivaroxaban and apixaban, do not require initial parenteral anticoagulation, but edoxaban does.62,66-69 The antithrombin inhibitor dabigatran also requires initial parenteral anticoagulation.67 These medications do not require monitoring, but they have specific dosing routines. Dosing for dabigatran is 150 mg twice daily by mouth, rivaroxaban 15 mg two times daily for 21 days then 20 mg once per day with food, and apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily.66-69 These NOACs do not require routine monitoring. Caution is warranted in patients older than 70 years and those with renal or hepatic disease. These agents are not approved for patients with massive PE or DVT, pregnancy, morbid obesity, active cancer, and serious thrombophilic defect.62,66-69

Bleeding Risk

Balancing risk of recurrent VTE and hemorrhage is necessary for outpatient therapy.62,65,70 Recurrent thrombus rate at one year can reach 27%, but the rate of fatal, major, and minor bleeding during therapy with warfarin is 0.6%, 3.0%, and 9.6%, respectively.71 One of the most feared complications is intracerebral hemorrhage, which is increased 7 to 10 fold with anticoagulation.72

The HAS-BLED score (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly (> 65 years), Drugs/alcohol concomitantly) was developed in 2010 to assess one year bleeding risk in patients with atrial fibrillation.70 This score has not evaluated risk of bleeding in patients with PE. Patients with < 1 point display a 3.4% risk of major bleeding in one validation study, while patients with scores > 3 points demonstrate a 5.8% risk of bleeding.65,73 This population warrants consideration of other therapies due to bleeding risk. This score possesses greater abilities to predict risk of major hemorrhage when compared to other scores.73-75 This score has been evaluated in patients with atrial fibrillation and not PE, but it does provide an easy means of evaluating bleeding risk.

Another tool for assessing hemorrhage risk for VTE outpatients with warfarin is the Outpatient Bleeding Risk Index (patient > 65 years, history of CVA, history of GI bleeding, recent MI, anemia, Cr > 1.5, or Diabetes).76-78 Major bleeding rates in the low, moderate, and high risk groups are 3%, 12%, and 48%, respectively, in the derivation set and 3%, 8%, and 30%, respectively, in the validation set.77,78

What should the emergency provider do?

Home treatment is feasible with VTE therapies that do not require hospitalization and scoring systems for risk stratification. Risk factors for adverse outcomes, patient ability to comply with treatment and successfully complete therapy, risk of major hemorrhage, and inpatient preferences with shared decision making should be considered.10-12,34,54

Patients with acute PE should undergo risk stratification first, and patients with any hemodynamic instability should be admitted.10,34,54 If the patient is hemodynamically stable, clinical scores can be used, with negative biomarkers. Elevation of these markers places the patient at intermediate-risk for adverse event. Multiple scores are present, and sPESI and ESC are easy to use with high sensitivity. PESI, GRS, and GRACE are difficult to use in the ED. The Hestia Criteria and Aujesky 2006 rule can be used, but they do not possess as much high quality evidence as other criteria. Class 1 and 2 PESI, negative Hestia, negative ESC, or negative sPESI patients are at low risk for PE-related all-cause mortality.10,34,54 If the patient has an alternative reason for admission, patient compliance is questionable, or psychosocial barriers are present, the patient warrants admission for treatment. Assessment for bleeding risk with HAS-BLED or Outpatient Bleeding Risk Index is recommended if considering discharge.70,76 Patients with HAS-BLED score < 1 or Outpatient Bleeding Risk Index score 0 have low risk of bleeding.70,76 If the patient desires outpatient therapy and is stable with adequate social situation, outpatient therapy is a feasible, safe option.

Case Conclusion:
The patient is low risk for adverse events based on sPESI, with negative biomarkers. The patient desires discharge home with treatment, and she appears to have an adequate social situation. You speak with her primary care physician over the phone, who is comfortable with the plan and will see her in several days. You provide a prescription for rivaroxaban and discharge the patient home.


-Patients with confirmed PE are classically admitted for treatment and monitoring of anticoagulation, with over 90% managed in-hospital.

-Literature suggests outpatient treatment is non-inferior, particularly with novel oral anticoagulants. Recurrent thromboembolism, risk of bleeding, and incidence of major adverse outcome are similar in patients treated as outpatient versus inpatient.

sPESI, PESI, and ESC possess strong literature support for outpatient PE stratification, with adequate sensitivity for predicting low risk adverse event.

-The HAS-BLED score and Outpatient Bleeding Risk Index allow assessment of bleeding risk.

Patient compliance, presence of psychosocial barriers, or alternative need for admission should be considered in patient disposition. Consideration of these important aspects with risk stratification and use of NOAC therapy can allow for safe, efficacious treatment as outpatient.

References/Further Reading

  1. Heit JA. The epidemiology of venous thromboembolism in the community: implications for prevention and management. J Thromb Thrombolysis 2006 Feb;21(1):23-9.
  2. Horlander KT, Mannino DM, Leeper KV. Pulmonary embolism mortality in the United States, 1979-1998: an analysis using multiple-cause mortality data. Arch Intern Med 2003; 163:1711.
  3. Silverstein MD, Heit JA, Mohr DN, et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998; 158:585.
  4. Naess IA, Christiansen SC, Romundstad P, et al. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost 2007; 5:692.
  5. Tagalakis V, Patenaude V, Kahn SR, Suissa S. Incidence of and mortality from venous thromboembolism in a real-world population: the Q-VTE Study Cohort. Am J Med 2013; 126:832.e13.
  6. Martinez C, Cohen AT, Bamber L, Rietbrock S. Epidemiology of first and recurrent venous thromboembolism: a population-based cohort study in patients without active cancer. Thromb Haemost 2014; 112:255.
  7. Hoffman JR, Cooper RJ. Overdiagnosis of disease: a modern epidemic. Arch Intern Med 2012 Aug 13;172(15):1123-4.
  8. Moynihan R, Doust J, Henry D. Preventing overdiagnosis: how to stop harming the healthy. BMJ 2012 May 28;344:e3502.
  9. Burge AJ, Freeman KD, Klapper PJ, Haramati LB. Increased diagnosis of pulmonary embolism without a corresponding decline in mortality during the CT era. Clin Radiol 2008 Apr;63(4):381-6.
  10. Keaton C, Akl EA, Ornelas J, Balizas A, et alt. Antithrombotic Therapy for VTE disease: CHEST Guideline. Chest 2016. DOI: 10.1016/j.chest.2015.11.026.
  11. Kline JA and Kabrhel C. Emergency Evaluation for Pulmonary Embolism, Part 1: Clinical Factors that Increase Risk. JEM 2015;48(6):771 – 780.
  12. Kline JA and Kabrhel C. Emergency Evaluation for Pulmonary Embolism, Part 2: Diagnostic Approach. JEM 2015;49(1):104-117.
  13. Newman DH, Schriger DL. Rethinking testing for pulmonary embolism: less is more. Ann Emerg Med 2011 Jun;57(6):622-627.
  14. Park B, Messina L, Dargon P, Huang W, Ciocca R, Anderson FA. Recent trends in clinical outcomes and resource utilization for pulmonary embolism in the United States: findings from the nationwide inpatient sample. Chest 2009 Oct;136(4):983-90.
  15. Bullano MF, Willey V, Hauch O, Wygant G, Spyropoulos AC, Hoffman L. Longitudinal evaluation of health plan cost per venous thromboembolism or bleed event in patients with a prior venous thromboembolism event during hospitalization. Manag Care Pharm 2005 Oct;11(8):663-73.
  16. Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. Lancet 1960;1:1309-12.
  17. Simonneau G, Sors H, Charbonnier B, et al. A comparison of low-molecular- weight heparin with unfractionated heparin for acute pulmonary embolism. N Engl J Med 1997;337:663-9.
  18. The Matisse Investigators. Subcutaneous fondaparinux versus intravenous un- fractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med 2003;349:1695-702.
  19. The van Gogh Investigators. Idraparinux versus standard therapy for venous thromboembolic disease. N Engl J Med 2007;357:1094-104.
  20. Koopman MM, Prandoni P, Piovella F, Ockelford PA, Brandjes DP, van der MJ, Gallus AS, Simonneau G, Chesterman CH, Prins MH. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group. N Engl J Med 1996; 334: 682–7.
  21. Levine M, Gent M, Hirsch J, Leclerc J, Anderson D, Weitz J, Ginsberg J, Turpie AG, Demers C, Kovacs M. A comparison of low-molecular- weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med 1996; 334: 667–81.
  22. The Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997; 337: 657–62.
  23. Dorfman GS, Cronan JJ, Tupper TB, Messersmith RN, Denny DF, Lee CH. Occult pulmonary embolism: a common occurrence in deep venous thrombosis. AJR Am J Roentgenol 1987; 148: 263–6.
  24. Kovacs MJ, Anderson D, Morrow B, Gray L, Touchie D, Wells PS. Outpatient treatment of pulmonary embolism with dalteparin. Thromb Haemost 2000; 83: 209–11.
  25. Kovacs MJ, Hawel JD, Rekman JF, Lazo-Langner A. Ambulatory management of pulmonary embolism: a pragmatic evaluation. J Thromb Haemost 2010; 8: 2406–11.
  26. Ong BS, Karr MA, Chan DK, Frankel A, Shen Q. Management of pulmonary embolism in the home. Med J Aust 2005;183(5):239–42.
  27. Olsson CG, Bitzen U, Olsson B, Magnusson P, Carlsson MS, Jonson B, Bajc M. Outpatient tinzaparin therapy in pulmonary embolism quantified with ventilation/perfusion scintigraphy. Med Sci Monit 2006;12(2):PI9–13.
  28. Rhodes S, Bond S. Shifting pulmonary embolism management to primary care. Nurs Times 2006;102(6):23–4.
  29. Stein PD, Fatta F, Hughes PG, Hourmouzis ZN, Hourmouzis NP, White RM, et al. Home Treatment of Pulmonary Embolism in the Era of Novel Oral Anticoagulants. Am J Med 2016 Sep;129(9):974-977.
  30. Baglin T. Fifty per cent of patients with pulmonary embolism can be treated as outpatients. J Thromb Haemost 2010; 8: 2404–5.
  31. Aujesky D, Mazzolai L, Hugli O, Perrier A. Outpatient treatment of PE. Swiss Med Wkly 2009;139(47–48):685–690.
  32. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax 2003;58(6): 470–83.
  33. Snow V, Qaseem A, Barry P, Hornbake ER, Rodnick JE, et al. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med 2007;146(3):204–10.
  34. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie N, Pruszczyk P, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008;29(18):2276–315.
  35. Aujesky D, Stone RA, Kim S, Crick EJ, Fine MJ. Length of hospital stay and post discharge mortality in patients with pulmonary embolism: a statewide perspective. Arch Intern Med 2008;168(7):706–12.
  36. Harrison L, McGinnis J, Crowther M, Ginsberg J, Hirsh J. Assessment of outpatient treatment of deep-vein thrombosis with low-molecular-weight heparin. Arch Intern Med 1998;158(18):2001–3.
  37. Aujesky D, Smith KJ, Cornuz J, Roberts MS. Cost-effectiveness of low-molecular-weight heparin for treatment of pulmonary embolism. Chest 2005;128(3):1601–10.
  38. From the Swiss Federal Statistical Office website. Available at: 1/data/01.html. Accessed April 15, 2015.
  39. Aujesky D, Roy PM, Verschuren F, Righini M, Osterwalder J, Egloff M, Renaud B, Verhamme P, Stone RA, Legall C, Sanchez O, Pugh NA, N’Gako A, Cornuz J, Hugli O, Beer HJ, Perrier A, Fine MJ, Yealy DM. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet 2011; 378: 41–8.
  40. Fang MC, Fan D, Sung S, et al. Outcomes in Adults With Acute Pulmonary Embolism Who Are Discharged From Emergency Departments: The Cardiovascular Research Network Venous Thromboembolism Study. JAMA Intern Med 2015;175(6):1060-1062.
  41. Yoo HH, Queluz TH, El Dib R. Outpatient versus inpatient treatment for acute pulmonary embolism. Cochrane Database Syst Rev 2014; 11: CD010019.
  42. Erkens PMG, Gandara E, Wells P, Shen AYH, Bose G, Le Gal G, Rodger M, Prins MH, Carrier M. Safety of outpatient treatment in acute pulmonary embolism. J Thromb Haemost 2010; 8: 2412–7.
  43. Zondag W, Vingerhoets LM, Durian MF, et al; Hestia Study Investigators. Hestia criteria can safely select patients with pulmonary embolism for outpatient treatment irrespective of right ventricular function. J Thromb Haemost 2013; 11(4):686-692.
  44. Vinson DR, Zehtabchi S, Yealy DM. Can selected patients with newly diagnosed pulmonary embolism be safely treated without hospitalization? A systematic review. Ann Emerg Med 2012 Nov;60(5):651-662.
  45. Beam DM, Kahler ZP, Kline JA. Immediate discharge and home treatment with rivaroxaban of low risk venous thromboembolism diagnosed in two U.S. emergency departments: a one-year preplanned analysis. Acad Emerg Med 2015;22:789–795
  46. Aujesky D, Roy PM, Le Manach CP, et al.  Validation of a model to predict adverse outcomes in patients with pulmonary embolism. Eur Heart J 2006;27 (4) 476- 481.
  47. Aujesky D, Perrier A, Roy PM, et al.  Validation of a clinical prognostic model to identify low-risk patients with pulmonary embolism. J Intern Med 2007;261(6): 597- 604.
  48. Jiménez D, Yusen RD, Otero R, et al.  Prognostic models for selecting patients with acute pulmonary embolism for initial outpatient therapy. Chest 2007;132 (1) 24- 30.
  49. Donzé J, Le Gal G, Fine MJ, et al.  Prospective validation of the Pulmonary Embolism Severity Index: a clinical prognostic model for pulmonary embolism. Thromb Haemost 2008;100 (5) 943- 948.
  50. Jiménez D, Aujesky D, Moores L, et al. Simplification of the Pulmonary Embolism Severity Index for Prognostication in Patients With Acute Symptomatic Pulmonary Embolism. Arch Intern Med 2010;170(15):1383-1389.
  51. Righini M, Roy PM, Meyer G, Verschuren F, Aujesky D, and Le Gal G. The Simplified Pulmonary Embolism Severity Index (SPESI): validation of a clinical prognostic model for pulmonary embolism. J Thromb Haemost 2011; 9: 2115-2117.
  52. Fermann GJ, Erkens PMG, Prins MH, et al. Treatment of Pulmonary Embolism With Rivaroxaban: Outcomes by Simplified Pulmonary Embolism Severity Index Score from a Post Hoc Analysis of the EINSTEIN PE Study. Acad Emerg Med 2015;22(3):299-307.
  53. Wicki J, Perrier A, Perneger TV, Bounameaux H, and Junod AF. Predicting adverse outcome in patients with acute pulmonary embolism: a risk score. Thromb Haemost 2000; 84:548-552.
  54. Kohn CG, Mearns ES, Parker MW, et al. Prognostic Accuracy of Clinical Prediction Rules for Early Post-Pulmonary Embolism All-Cause Mortality: A Bivariate Meta-analysis. Chest 2015 Apr 1;147(4):1043-62.
  55. Paiva LV, Providencia RC, Barra SN, Faustino AC, Botelho AM, Marques AL. Cardiovascular risk assessment of pulmonary embolism with the GRACE risk score. Am J Cardiol 2013;111(3):425-431.
  56. Maestre A, Trujillo-Santos J, Riera-Mestre A, Jiménez D, Di Micco P, RIETE Investigators. Identification of Low-Risk Patients with Acute Symptomatic Pulmonary Embolism for Outpatient Therapy. Ann Am Thorac Soc 2015 Aug;12(8):1122-9.
  57. Lankeit M, Jimenez D, Kostrubiec M, Dellas C, Kuhnert K, Hasenfuss G, Pruszczyk P, Konstantinides S. Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism. Eur Respir J 2014; 43: 1669–77.
  58. Jimenez D, Kopecna D, Tapson V, Briese B, Schreiber D, Lobo JL, Monreal M, Aujesky D, Sanchez O, Meyer G, Konstantinides S, Yusen RD, On Behalf of the Protect I. Derivation and validation of multimarker prognostication for normotensive patients with acute symptomatic pulmonary embolism. Am J Respir Crit Care Med 2014; 189: 718–26.
  59. Singanayagam A, Scally C, Al-Khairalla MZ, Leitch L, Hill LE, Chalmers JD, Hill AT. Are biomarkers additive to pulmonary embolism severity index for severity assessment in normotensive patients with acute pulmonary embolism? QJM 2011; 104: 125–31.
  60. Sanchez O, Trinquart L, Planquette B, Couturaud F, Verschuren F, Caille V, Meneveau N, Pacouret G, Roy PM, Righini M, Perrier A, Bertoletti L, Parent F, Lorut C, Meyer G. Echocardiography and pulmonary embolism severity index have independent prognostic roles in pulmonary embolism. Eur Respir J 2013; 42: 681–8.
  61. Moores L, Aujesky D, Jimenez D, Diaz G, Gomez V, Marti D, Briongos S, Yusen R. Pulmonary embolism severity index and troponin testing for the selection of low-risk patients with acute symptomatic pulmonary embolism. J Thromb Haemost 2010; 8: 517–22.
  62. Pollack C. New oral anticoagulants in the ED setting: a review. Am J Emerg Med 2012;30:2046-2054.
  63. The EINSTEIN–PE Investigators. Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism. N Engl J Med 2012; 366:1287-1297.
  64. Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 369(9):799-808.
  65. Loffredo L, Perri L, Del Ben M, et al. New oral anticoagulants for the treatment of acute venous thromboembolism: are they safer than vitamin K antagonists? A meta-analysis of the interventional trials. Intern Emerg Med 2015;10:499-506.
  66. Lovenox (package insert). Sanofi-Aventis, Bridgewater, NJ; 2011.
  67. Pradaxa [package insert]. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT; 2011.
  68. Xarelto [package insert]. Janssen Pharmaceuticals, Inc., Titusville, NJ; 2011.
  69. Eliquis [summary of product characteristics]. Bristol-Myers Squibb/Pfizer EEIG, Middlesex, UK; 2011.
  70. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010 Nov;138(5):1093-100.
  71. Kearon C, Gent M, Hirsh J, et al.  Extended anticoagulation compared to placebo after three months of therapy for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999;34:901-907.
  72. Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage. Facts and hypotheses. Stroke 1995; 26:1471-1477.
  73. Lip GH, Frison L, Halperin JL, Lane DA. Comparative Validation of a Novel Risk Score for Predicting Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation: The HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) Score. J Am Coll Cardiol 2011;57(2):173-180.
  74. Apostolakis S, Lane DA, Guo Y, Buller H, Lip GY. Performance of the HEMORR(2)HAGES, ATRIA, and HAS-BLED bleeding risk-prediction scores in patients with atrial fibrillation undergoing anticoagulation: the AMADEUS (evaluating the use of SR34006 compared to warfarin or acenocoumarol in patients with atrial fibrillation) study. J Am Coll Cardiol 2012 Aug 28;60(9):861-7.
  75. Roldán V, Marín F, Fernández H, et al. Predictive Value Of The Has-Bled And Atria Bleeding Scores For The Risk Of Serious Bleeding In A “Real-World” Population With Atrial Fibrillation Receiving Anticoagulant Therapy. Chest 2013;143(1):179-184.
  76. Wells PS, Forgie MA, Simms M, et al. The Outpatient Bleeding Risk Index: Validation of a Tool for Predicting Bleeding Rates in Patients Treated for Deep Venous Thrombosis and Pulmonary Embolism. Arch Intern Med 2003;163(8):917-920.
  77. Landefeld CS, Rosenblatt MW, Goldman L. Bleeding in outpatients treated with warfarin: relation to the prothrombin time and important remediable lesions. Am J Med 1989;87:153- 159.
  78. Beyth RJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 1998;10:591-99.

FOAMed Resources Part VIII: EMS/Prehospital

Authors: Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC) and Manpreet Singh, MD (@MPrizzleER – Associate Editor-in-Chief; Assistant Professor in Emergency Medicine / Department of Emergency Medicine – Harbor-UCLA Medical Center) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital)

The Prehospital environment is where emergency medicine begins. These providers are paramount in the initial stages of evaluation and management of critically ill patients. While most providers in the ED have medical or trauma rooms with adequate equipment and space, this is not the case for EMS. The stress, situation, and patient all present significant challenges to care providers.

The following list is comprised of blogs/podcasts with great education pearls, valid content, and major impact on EM, with clear reference citation. If you have found other great resources, please mention them in the comments below!




Prehospital and Retrieval Medicine (PHARM) from Minh Le Cong is a fantastic prehospital resource with podcast and blog. Posts center on transport/retrieval medicine, airway, sedation, and prehospital critical care. This resource is a must for those with interest in airway, sedation, and EMS. Each podcast and blog post is well researched, providing succinct keys to success.




Scott Weingart’s blog and podcast contain several posts on cutting edge prehospital topics and procedures. REBOA, amputation care, hemostatic resuscitation, airway, sedation, hypothermia, and many more controversial topics are covered. These posts are well researched, with citations to the primary studies. Many of the prehospital podcasts contain interviews with experts in the field of prehospital medicine.




Fire EMS Blogs is a network of sites covering EMS, rescue, hazmat, command, and training from San Diego. A wide variety of blogs are available including discussion of interesting cases, ECG interpretation, life as an EMS provider, and evidence-based medicine.




HEMS Critical Care from Philip Neuwirth brings together posts from blogs around the FOAMed universe pertaining to EMS/prehospital medicine into one place. If you’re interested in prehospital medicine and don’t have the time to regularly look through multiple online blogs, this resource does it for you.




Taming the SRU is an all-around great resource concerning emergency medicine. The podcast and blog’s prehospital page covers topics including out-of-hospital cardiac arrest, stroke care, trauma, and STEMI. Posts and podcasts are thorough, and each podcast has a summary in bullet format.




EMFirst is dedicated to first responders and prehospital providers. Benjamin Ayd and Pratik Das cover classic and cutting edge EMS topics including TXA, REBOA, trauma, and ketamine. Not many posts are up now, but this site has a ton of potential.




Medic Nerd from founder Mike Stewart seeks to provide enjoyable and effective EMS education through videos and blog posts. Videos explain physical exam findings, IV drip rates, prehospital procedures, interesting cases, and controversial studies. For those studying for a qualifying exam, flashcards are also provided (




Prehospital wisdom from Denver Paramedics is a blog with posts on EMS runs, interesting cases, and ECGs. Controversies in prehospital medicine are investigated, including C-spine protection, adenosine, distracting injury definition, and many others.




RESUS.ME has a complete prehospital section with EMS procedures, literature, and conferences. Posts provide key prehospital literature updates in a format that illuminates the key takeaways.




EMS 12-Lead is a leading resource for and by paramedics who are interested in all things EKG. Check out their posts to see EKG and cardiac rhythm analysis for patients in the field, and you can also submit your own case.




SCANCRIT is a blog covering anesthesia, critical care, and emergency medicine, with a focus on the critically ill patient. Posts are written by two Scandinavian anesthesiologists, who evaluate in-hospital and out-of-hospital medicine. Recent posts have investigated GCS, VF, hemorrhage evaluation and management, brain bleeds, and ATLS updates.

Thanks for reading our look at EMS resources. Comment below with other helpful sites!