Emergency Medicine Executive Summary

N-Acetylcisteine (NAC) is a mucolytic, antioxidant and a glutathione-inducer. It is positioned as the cornerstone antidote for the prevention and treatment of liver toxicity secondary to acetaminophen (APAP) overdose, with US-FDA approval for IV and PO administration.

• Adult and Pediatric dose for acetaminophen overdose: oral administration, 18 doses total.

• Loading dose: 140mg/kg PO.

• Dose 2 to 17: repeated doses every 4 hours of 70mg/kg PO.

Emergency Medicine Excecutive Summary

Fibrin-specific Tissue Plasminogen Activator (fibrinolytic) is widely accepted for emergency revascularization in acute myocardial infarction (MI), high risk acute pulmonary embolism (PE), and acute ischemic stroke (AIS). In emergency medicine it is also used in intermediate-high risk PE and cardiac arrest when there is a high suspicion of MI or PE as the cause, in both scenarios the decision should be taken cautiously and in very selected cases.

Always seriously consider the contraindications and balance the risk of intracranial and other major bleeding events versus the benefit of the therapy. Fibrinolysis is an intervention that should be decided -or at least supported- by a specialist (emergency medicine, neurologist, cardiologist, intensivist).

Dosing Summary

Acute Coronary Syndrome with ST elevation (<12 hours)

FDA approved.

Adult dose:

• ≤67kg: 15mg bolus + 0.75mg/kg in next 30 min

• >67kg: 15 mg bolus + 50 mg in 30 min + 35 mg in 60 min

Acute Ischemic Stroke (<4.5 hours)

FDA approved for <3 hours after symptom onset (1996), Universally accepted use in <4.5 hours.
Adult dose:

• <100kg: 0.09mg/kg bolus + 0.81mg/kg 60min

• >100kg: 9mg bolus + 81mg 60min

Pulmonary Embolism

FDA approved.

Adult dose:

• Intermediate risk: 50mg in 2 hrs

• High risk: 100mg in 2 hrs

• Cardiac arrest: 50mg bolus + 50mg if no ROSC in 15 min

Emergency Medicine Executive Summary

Ciclobenzaprine is a centrally acting skeletal muscle relaxant widely prescribed to relieve acute painful musculoskeletal conditions as an adjunct treatment to physical therapy and rest. It is also used as a temporary adjuvant medication along with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen.

• Limited data supports its use in the short term for treating acute muscle spasm, acute low back pain, fibromyalgia and temporomandibular disorder.

• Muscle relaxants including cyclobenzaprine have significant adverse effects on the central nervous system (sedation, drowsiness, dizziness), therefore, they should be prescribed with caution and their benefits need to be balanced with their risks; experts differ on whether they should be used or not.

• It has a similar structure to tricyclic antidepressants such as amitriptyline, thus it can cause serious anticholinergic effects, but no direct cardiotoxicity has been reported in cases of overdose (eg. sodium channel blockade and QRS complex widening).

Adult dose for acute painful musculoskeletal spasms

• Immediate release formulation

  • 5mg TID with one dose at night.

  • Maximum 30mg/day, up to 2-3 weeks.

• Extended release formulation

  • 10-15mg once daily at bedtime.

  • Maximum 30mg/day, up to 2-3 weeks.

• Many clinicians start at a low dose at night (5mg) and then titrate up if it is strictly necessary.

Emergency Medicine Executive Summary

Etomidate is one of the most used and preferred hypnotic agents in the Emergency Department (ED) for Rapid Sequence Intubation (RSI), despite the US-FDA pending label for this indication.

• Etomidate acts on GABA receptors moderating the activity of chloride channels; it makes neurons less excitable without any major cardiovascular impact. This feature suits etomidate for the great majority of emergency scenarios in which advanced airway management is required.

• Its use in sepsis has been challenged because of the dose-dependent adrenal inhibition of corticosteroid synthesis, therefore only a single bolus dose is recommended for induction –not as a maintenance infusion– but to minimize adrenal suppression.

• Myoclonic movements are a common adverse effect; they are observed for 1 to 3 minutes and cease spontaneously. In practice, the movements usually stop shortly after neuromuscular blockage and lack any clinical significance.

Pharmacology for a single bolus administration:

• Onset: 15-45 seg

• Time to Peak Effect: 45 seg

• Duration of hypnotic effect: 3-12 min

• Half life: 2-5h

• Adult dose for rapid sequence intubation:
  0.3mg/kg IV (total body weight).
  Consider a lower dose of 0.2mg/kg in profound shock.

Emergency Medicine Executive Summary

Lorazepam is an intermediate acting benzodiazepine (BDZ) –a GABA receptor enhancer– with CNS depressant effects including sedative, hypnotic, skeletal muscle relaxing and anticonvulsant activity. It can be administered either by intravenous, intramuscular, sublingual or oral routes. Along with midazolam and clonazepam, lorazepam is one of the most frequently indicated BDZs in the ED.

Sedation timing with single 2-4mg dose:

• Intravenous

Onset (IV): 5-10 minutes*

Peak Effect (IV): 30 minutes

Duration (IV): 2-6 hours

(*shorter to terminate seizures)

• Intramuscular

Onset (IM) 15 minutes

Peak Effect (IM) 60 minutes

Duration (IM) 6-8 hours

Dosing

• Adult dose for status epilepticus:
  0.1mg/kg IV (max 4mg/dose).
  Repeat every 5-10 min until the crisis has ceased.
  Consider initiating an antiepileptic if a second lorazepam dose is required.

• Adult dose for undifferentiated agitation:
  2-4mg sublingual, IV or IM as needed (if severely agitated, IM route is prefered).
  Repeat every 20-30 min if necessary.
  The BDZ of choice to treat severe undifferentiated agitation is considered to be midazolam IM for its faster onset of action.

• Acute anxiety disorder:
  0.5-2mg sublingual, PO or IV as needed.
  Repeat every 20-30 minutes if necessary.

Emergency Medicine Executive Summary

Norepinephrine (NE) is used for hemodynamic support frequently as a first-line vasopressor with the exception of anaphylaxis (epinephrine) and post cardiac arrest care (epinephrine). Consider using noradrenaline in combination with inodilator drugs in cardiogenic shock.

• Adult dose for shock:
  Calculate with total body weight.
  Norepinephrine 0.01-0.3 ug/kg/min IV.
  Usually started at 0.05 ug/kg/min IV.

Emergency Medicine Executive Summary

Olanzapine is a second generation (atypical) antipsychotic with a potent antagonism of serotonin 5-HT2A, 5-HT2C, dopamine D1-4, histamine H1 and alpha1-adrenergic receptors. It also has a moderate antagonism of muscarinic M1-5 receptors, as well as a weak agonism to GABA-A, BZD and beta-adrenergic receptors.

In the ED, olanzapine is frequently indicated as a first-line antipsychotic for acute agitation associated with psychiatric disorders (US FDA and EMA approved for agitation in individuals with schizophrenia and bipolar disorder). Agitation in the ED is a very complex situation that includes a variety of dissimilar scenarios with a wide range of therapeutic options. Many clinical guidelines have been proposed with substantial differences between them; as emergency physicians, it is of great importance to be familiarized with the available therapeutic arsenal for agitation, such as haloperidol, droperidol, benzodiazepines, propofol, ketamine, etc.

• Adult dose for severe agitation:
  5 to 10mg IM, repeated every 20 min if necessary, with a maximum of 30mg/day for intramuscular administration.

Emergency Medicine Executive Summary

Phentolamine is a vasodilator used to prevent tissue necrosis caused by extravasated catecholamine infusions (epinephrine, norepinephrine, dopamine, etc). Available in the US. Limited stock in Canada. Unavailable in Chile.

• Adult dose:
  5-10mg diluted in 10-20ml of NaCl 0.9% subcutaneous immediately after extravasation (use within 12 hours).

Emergency Medicine Executive Summary

Rabies is a zoonotic disease positioned as one of the most lethal viral infections; mortality approaches 100%. It is also preventable in nearly 100% of expositions when vaccination has been properly administered.

• Adult and pediatric vaccination regimen for post-exposure prophylaxis (PEP)

• Immunocompetent without prior rabies immunization:
  4 doses IM, days 0-3-7 and 14*

• Immunocompromised without prior rabies immunization:
  5 doses IM, days 0-3-7-14 and 28

• Prior rabies immunization**:
  2 doses IM, days 0 and 3

*Some regions and their local guidelines still recommend a universal 5-dose regimen for PEP as previously was recommended by the US-CDC, and currently some manufacturers.

**Complete 4 doses of PEP scheme or 3 doses of PrEP (pre-exposure prophylaxis).

Acute Myocardial Infarction with ST elevation (STEMI <12hrs)

FDA approved, 2000. Indicated when anticipated STEMI diagnosis to Percutaneous Coronary Intervention-mediated reperfusion time is >120min.

Adult dose (IV ,bolus):

• <60 kg 30mg

• 60 - 69 kg 35mg

• 70 - 79 kg 40mg

• 80 - 89 kg 45mg

• ≥90 kg 50mg

Acute Ischemic Stroke (AIS <4.5hrs)

Not FDA approved.

Adult dose (IV ,bolus):

• AIS eligible for mechanical thrombectomy

  • 0.25mg/kg bolus (max 25mg)

• AIS with minor neurological impairment uneligible for a mechanical thrombectomy

  • 0.4mg/kg bolus

Pulmonary Embolism (PE)

Not FDA approved. Prefer alteplase for PE fibrinolytic therapy. If unavailable, consider tenecteplase.

Adult dose (IV, bolus):

• <60 kg 30mg

• 60 - 69 kg 35mg

• 70 - 79 kg 40mg

• 80 - 89 kg 45mg

• ≥90 kg 50mg

Emergency Medicine Executive Summary

Tetanus Immune Globulin (TIG) is indicated for tetanus disease treatment and prophylaxis (the latter in individuals without updated or an unknown tetanus immunization who have suffered a contaminated or a tetanus-prone wound).

• Adult dose:

• Tetanus treatment:
  500 units IM with part of the dose infiltrated close to the source wound. Up to 6000 units can be used.

• Tetanus prophylaxis:
  250 units IM (single dose).

Thiamine (vitamin B₁) is a water-soluble vitamin that is essential in the creation and utilization of cellular energy related to aerobic glycolysis in the citric acid cycle. Its deficiency leads to cardiovascular (heart failure) and neurologic disease (Wernicke - Korsakoff syndrome, "WK"). In the ED thiamine is frequently indicated in the prevention and treatment of WK, mainly in patients with ethanol dependence and/or malnutrition.

Adult dose for WK prevention and treatment

• WK prevention

  • 100-250mg IV daily for 3-5 days, then consider daily PO supplementation

• WK treatment

  • 500mg IV every 8 hours for 3-5 days, then 250mg IV daily for 3-5 days, then indefinitely daily PO supplementation

  • Always supplement with magnesium (2gr MgSO₄ daily)

Emergency Medicine Executive Summary

The antifibrinolytic agent tranexamic acid (TXA) is a synthetic lysin derivative that binds plasminogen and plasmin, blocking their interaction with fibrin (4). It is indicated extensively in the ED for a variety of bleeding scenarios.

• The most validated usage is in patients with acute trauma with a suspected severe hemorrhage (1, 3, 5, 7, 12). Currently it is an established component of “damage control resuscitation” (3, 5, 9).

• All-cause mortality reduction was proven by the game-changer CRASH-2 trial –a strong double-blind RCT that compared TXA versus a placebo in trauma, based on the uncertainty principle (attending physician not being sure if TXA was beneficial or not)(1)–. Afterwards other studies have documented improved survival rates (3, 7, 11).

• Later on TXA was studied in acute traumatic brain injury (TBI). It was found to have a limited potential benefit in reducing head injury associated deaths in mild to moderate TBI (6). Nonetheless TXA was recently indicated and included for TBI in combat medical guidelines (8, 9).

Adult dose for trauma with risk of significant hemorrhage

1gr in 10 min IV + 1gr in 8 hrs IV.

• Available an in-depth review of etomidate.

• The optimal dosing adjustments in obese patients are still on debate and authors support different modalities, those recommended in the table represent the most frequently accepted corrections by the literature. We also agree on those corrections based on expert opinion and clinical experience in emergency medicine. For more information follow this link.

TBW Total body weight
IBW Ideal body weight
NMDA N-methyl-D-aspartate (receptor)
RSI Rapid Sequence Intubation

1. Brunette DD. Resuscitation of the morbidly obese patient [published correction appears in Am J Emerg Med. 2004 May;22(3):248]. Am J Emerg Med. 2004;22(1):40-47. doi:10.1016/s0735-6757(02)42250-4.
   Pubmed

2. Miller, Ronald D. Miller's Anesthesia. 8th edition. Philadelphia, PA: Churchill Livingstone/Elsevier; 2015.
   Elsevier

3. Brown CA, Sakles JC, Mick NW. The Walls Manual of Emergency Airway Management. 5th edition. Philadelphia, PA. Wolters Kluwer; 2018.
   Wolters Kluwer

4. Cabrera JL, Auerbach JS, Merelman AH, Levitan RM. The High-Risk Airway. Emerg Med Clin North Am. 2020;38(2):401-417. doi:10.1016/j.emc.2020.01.008.
   Pubmed

5. Manning S. The Crashing Obese Patient. Emerg Med Clin North Am. 2020;38(4):857-869. doi:10.1016/j.emc.2020.06.013.
   Pubmed

6. Erstad BL, Barletta JF. Drug dosing in the critically ill obese patient-a focus on sedation, analgesia, and delirium. Crit Care. 2020;24(1):315. Published 2020 Jun 8. doi:10.1186/s13054-020-03040-z.
   Pubmed

AIS Acute ischemic stroke

FDA (US) Food and Drug Administration

MI Myocardial infarction

PE Pulmonary embolism

ROSC Return of spontaneous circulation

1. GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993;329(10):673-682. doi:10.1056/NEJM199309023291001
   Pubmed

2. NINDS - National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333(24):1581-1587. doi:10.1056/NEJM199512143332401
   Pubmed

3. ASSENT 2 - Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) Investigators, Van De Werf F, Adgey J, et al. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet. 1999;354(9180):716-722. doi:10.1016/s0140-6736(99)07403-6
   Pubmed

4. ECASS III - Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317-1329. doi:10.1056/NEJMoa0804656
   Pubmed

5. NOR-TEST - Logallo N, Kvistad CE, Nacu A, et al. The Norwegian tenecteplase stroke trial (NOR-TEST): randomised controlled trial of tenecteplase vs. alteplase in acute ischaemic stroke. BMC Neurol. 2014;14:106. Published 2014 May 15. doi:10.1186/1471-2377-14-106
   Pubmed

6. EXTEND-IA-TNK - Campbell BC, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): A multicenter, randomized, controlled study. Int J Stroke. 2018;13(3):328-334. doi:10.1177/1747493017733935
   Pubmed

7. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association [published correction appears in Stroke. 2018 Mar;49(3):e138] [published correction appears in Stroke. 2018 Apr 18;:]. Stroke. 2018;49(3):e46-e110. doi:10.1161/STR.0000000000000158
   Pubmed

8. Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119-177. doi:10.1093/eurheartj/ehx393
   Pubmed

9. EXTEND-IA-TNK Part 2 - Campbell BC, Mitchell PJ, Churilov L, et al. Determining the optimal dose of tenecteplase before endovascular therapy for ischemic stroke (EXTEND-IA TNK Part 2): A multicenter, randomized, controlled study. Int J Stroke. 2020;15(5):567-572. doi:10.1177/1747493019879652
   Pubmed

10. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603. doi:10.1093/eurheartj/ehz405
    Pubmed

• WHO - Model List of Essential Medicines 2019
  https://www.who.int/(...)

• US FDA - Approved Drugs Orange Book 2021
  https://www.accessdata.fda.gov/(...)

• EMA - European Medicines Agency - Covid-19 Updates 2021
  https://www.ema.europa.eu/(...)

• ACEP - American College of Emergency Physicians - Clinical Policies
  https://www.acep.org/(...)

• EUSEM - European Society for Emergency Medicine - Guidelines for the management of acute pain in emergency situations 2020
  https://eusem.org/(...)

• RCEM - The Royal College of Emergency Medicine - Clinical Guidance
  https://www.rcem.ac.uk/(...)