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, PO and effervescent tablets 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.

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Executive Summary
Alteplase, a 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). 

Acute Coronary Syndrome with ST elevation (<12 hours)

US-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)

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

• <100kg:  0.9mg/kg total (max 90mg)

  • 10% bolus over 1 min

  • 90% infusion over 60 min

• ≥100kg: 9mg bolus + 81mg 60min

Pulmonary Embolism

US-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

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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.

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

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Executive Summary

Droperidol is a first generation antipsychotic (so-called typical antipsychotics, same class as haloperidol) that acts as a D2 dopamine receptor antagonist. Droperidol also has some histamine and serotonin antagonist properties. 

• It has a significant potential role in the ED because of its efficacy to treat a variety of clinical conditions, including undifferentiated agitation, migraine, vertigo, nausea, vomiting, cannabinoid hyperemesis, and pain.

• The US-FDA issued a Black Box Warning in 2001, but has been deeply questioned. This is why the drug has been regaining popularity and its use has been increasing over the last decade. Nonetheless it should not be used on patients with long QT syndrome or at an increased risk of QT prolongation. 

Adult dose for undifferentiated agitation in the ED

5-10mg IM

Adult dose for migraine, acute vertigo, nausea or vomiting and cannabinoid hyperemesis

1.25-2.5mg IV or IM

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Executive Summary
Etomidate is an ultrashort-acting, non-barbiturate hypnotic intravenous anesthetic agent. Is one of the most used and preferred hypnotic agents in the ED for Rapid Sequence Intubation. 

• Etomidate acts on GABA receptors moderating the activity of chloride channels; it makes  neurons less excitable without any major cardiovascular impact.

• It causes an adrenal inhibition of corticosteroid synthesis, therefore only a single  bolus dose is recommended for induction to minimize adrenal suppression. 

Pharmacology for a single bolus administration:

• Onset: 15-45 seg

• Time to Peak Effect: 45 seg

• Duration of hypnotic effect: 3-12 min

Adult dose for rapid sequence intubation:  

0.3mg/kg IV (total body weight).

• Consider a lower dose of 0.2mg/kg in profound shock. 

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Executive Summary

Epinephrine is an endogenous catecholamine non-selective agonist of all adrenergic receptors with a major role in emergency medicine on a variety of different diagnoses. 

• Anaphylaxis
  Epinephrine acts on several pathophysiological pathways that cause anaphylaxis . It is the only established therapy to treat this condition.

• Cardiac arrest (CA)
  Current guidelines include epinephrine as part of standard treatment during CA in children and adults, being the only recommended drug regardless of initial rhythm mainly because it is associated with an increased rate of ROSC* and short-term survival. 

• Severe asthma crisis
  Consider IV or IM epinephrine in the crashing asthmatic patient to deliver a systemic Beta-2 agonist agent (when inhaled bronchodilators have trouble getting into the lower airway). Give as a push-dose if administered IV, and an equivalent anaphylaxis dose for IM administration.

*ROSC: Return of Spontaneous Circulation

Adult dose for anaphylaxis
0.01mg/kg (max 0.5mg per dose) IM into the anterolateral aspect of the thigh.

• Can be repeated every 5-15 min if necessary.

• If there is no response, consider a continuous IV infusion of epinephrine.

Adult dose for cardiac arrest
1mg every 3 to 5 minutes IV or IO

• In shockable rhythms early defibrillation should be performed as soon as possible, before any other resuscitation interventions

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Executive Summary

Hypertonic saline solutions (HTS) are electrolyte concentrates of NaCl (over 0.9%) and  considered to be high alert medications that are cautiously used to treat symptomatic hyponatremia and acute intracranial hypertension (IH) secondary to multiple causes, but mainly to traumatic brain injury. 

• Recent reviews comparing mannitol versus HTS tend to favor the latter with a weak level of evidence. 

• Ideally HTS should be administered through a central venous access, but in emergency situations, peripheral infusions have been determined to be a safe short-term alternative, but a close monitoring of the clinical response and sodium levels is warranted to guide subsequent doses.  

Adult dose for acute intracranial hypertension caused by TBI

NaCl 3%, 2 ml/kg IV in 15 minutes bolus

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Executive Summary

Ketorolac is an NSAID with a potent analgesic effect that is very frequently indicated in the ED worldwide to treat moderate to severe acute pain. 

• The US-FDA labeling recommends usage only for moderate to severe pain (defined as requiring analgesia at the opioid level), and for a short period of time of no more than 5 days to reduce NSAIDs adverse effects.

• Ketorolac, as well as other NSAIDs, reduces opioid requirements for acute pain.

Adult dose for acute moderate to severe pain

• IV: 10 to 30mg every 6 hours IV (max 120mg/day)*

• PO: 10mg every 6 hours PO (max 40mg/day)

*adults ≥65 years: max 60mg/day

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Executive Summary

Levetiracetam (LEV) is a second generation antiepileptic drug (AED) that has gained popularity in the ED for the treatment of status epilepticus (with a conjunction of benzodiazepines, usually IV lorazepam or IM midazolam); 

• It modulates neuronal activity through GABA and high-voltage-dependent calcium channels, by unknown molecular mechanisms.

• In children and adults, compared with other AED, LEV has a similar efficacy treating SE, with an excellent safety profile (most studies comparing it with phenytoin).

• EMDrugs is currently reviewing evidence regarding LEV usage for seizure prophylaxis in traumatic brain injury and subarachnoid hemorrhage. 

Adult dose for status epilepticus

Loading dose of 60mg/kg IV (max 4,500mg) in 15 minutes. 

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Executive Summary
Lidocaine is a synthetic local anesthetic, and one of the most frequently used drugs in the ED.  It has a reversible blocking effect on voltage-gated sodium channels, resulting in two main clinical usages: (i) interrupting nerve impulse propagation to achieve local or regional anesthesia, and (ii) inhibition of cardiac ion channels as a class IB antiarrhythmic drug. 

• Lidocaine has a wide variety of specific applications in the ED: 

• Antiarrhythmic for ventricular tachycardia

• Local and regional anesthesia for wound repair and fracture closed reductions

• Pain management for severe painful conditions such as renal colic and headache 

• Topical –spray or gel– anesthesia for awake intubation and other procedures such as bladder catheterization 

• Symptomatic treatment of cough

• Transdermal patches to alleviate post-herpetic neuralgia and rib fractures

Adult dose for local anesthesia

Up to 4.5 mg/kg (max 300mg per dose) subcutaneous infiltration within 2 hours.

• Dosing calculator: MDCalc®   - Local Anesthetic Dosing Calculator

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Executive Summary

Intravenous lipid emulsion (IVLE) is a nutritional supplement approved by the US-FDA for parenteral nutrition, that have promising results for the treatment of lipophilic agents toxicity, mostly for local anesthetic systemic toxicity (LAST).

• In conjunction with advance cardiovascular and neurocritic support, toxicologists and AHA guidelines consider IVLE as a valid therapeutic option to treat LAST, particularly in severe cases (eg. cardiovascular collapse / arrest).

Adult dose for Local Anesthetic Systemic Toxicity (LAST)

Intralipid® 20%, 1,5 ml/kg IV bolus over 1 minute (approximately 100ml in adults), followed by an infusion of 0.25ml/kg/min IV over the next 30-60 minutes.

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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

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.

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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:
0.01-0.3 ug/kg/min IV

• Usually started at 0.05 ug/kg/min IV

• Calculate with total body weight

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Executive Summary
Olanzapine is a second generation (atypical) antipsychotic with a potent antagonism of serotonin, dopamine, histamine and alpha1-adrenergic receptors. 

• In the ED, olanzapine  is frequently indicated as a first-line antipsychotic for acute agitation associated with psychiatric disorders.

• Agitation in the ED is a very complex situation that includes a variety of dissimilar scenarios with a wide range of therapeutic options. It is of great importance to be familiarized with the available therapeutic arsenal for agitation, such as droperidol, benzodiazepines, ketamine, etc. 

Adult dose for severe agitation:
5 to 10mg IM, repeated every 20 min if necessary

• Maximum of 30mg/day for intramuscular administration. 

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

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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).

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Executive Summary

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

  • Under revision due to NOR-TEST 2 trial results (2022)

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

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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 for tetanus treatment and prophylaxis

• 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).

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Executive Summary
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)

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Executive Summary

The antifibrinolytic agent tranexamic acid (TXA) is a synthetic lysin derivative that binds plasminogen and plasmin, blocking their interaction with fibrin. 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. Currently it is an established component of “damage control resuscitation”. 

• 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)–. Afterwards other studies have documented improved survival rates.

Adult dose for trauma with risk of significant hemorrhage

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

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• ISMP - Institute for Safe Medication Practices
  https://www.ismp.org/ 

• WHO - World Health Organization 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 2023
  https://www.ema.europa.eu/(...)

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

• AAEM - American Academy of Emergency Medicine - Clinical Practice Statements
  https://www.aaem.org/(...)

• CAEP - Canadian Association of Emergency Physicians - Clinical Practice Guidelines
  https://caep.ca/(...)

• 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/(...)

• ASHP - American Society of Health-System Pharmacists - Guidelines on Emergency Medicine Pharmacist Services
  https://www.ashp.org/(...)