Executive Summary

N-Acetylcysteine (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.

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

• Loading dose: 140 mg/kg PO.

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

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Executive Summary

Activated charcoal (AC) is a nonspecific adsorbent extensively used in EDs to reduce the absorption and prevent the enterohepatic recirculation of various toxic substances and drug overdoses.

• There is a tendency to use it in a more rational fashion, balancing potential benefits with risks. Ideally, it should be administered within 1 hour of ingestion; however, this limit may vary in cases involving extended-release forms of ingested xenobiotics and other exceptions.

  • AC is indicated for toxic doses of acetaminophen, aspirin, antidepressants, antipsychotics, antiepileptic drugs, calcium channel blockers, beta-blockers, etc.

• Cautions: evaluate the level of consciousness and airway to prevent aspiration; secure the airway before administration if necessary. Activated charcoal is contraindicated in cases of gastrointestinal obstruction or perforation.

  • Not useful in acids, alkali, alcohols, hydrocarbons, heavy metals, pesticides, etc.

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Adult single dose of AC for acute poisoning / drug overdose

• 1 gr/kg PO.

• Dilute in water or flavored juice.

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Executive Summary

Adenosine is an endogenous nucleoside present in all human cells. It is categorized as a “class V” or “miscellaneous” antiarrhythmic agent, as it does not meet the criteria for inclusion in antiarrhythmic classes I, II, III, or IV.

• Adenosine is the first-line medication for stable paroxysmal supraventricular tachycardia (PSVT) unresponsive to vagal maneuvers, commonly used in EDs worldwide.

• It decreases conduction through the AV node, thereby terminating the PSVT in 90% of cases.

• Always administer adenosine in the resuscitation room with continuous monitoring and a defibrillator at hand.

• Cautions:

  • Contraindications: 2nd or 3rd AV block, sinus node disease and symptomatic bradycardia, and irregular wide-complex tachycardia as it may trigger ventricular fibrillation.

  • Interactions: use with extreme caution if the patient has received other antiarrhythmics or AV blocking agents.

  • Adverse effects: flushing, dizziness, shortness of breath, chest pain or discomfort, transient hypotension, etc. Various self-limited arrhythmias, AV blocks, or prolonged sinus pause at the time of sinus conversion. It may cause bronchoconstriction.

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Adult dose for paroxysmal supraventricular tachycardia

“6-12-12 mg”

• Initial dose: 6 mg IV given as a rapid bolus, immediately followed by a vigorous flush of normal saline.

• If a second dose is needed: 12 mg IV as a rapid bolus.

• If a third dose is needed: 12 mg IV as a rapid bolus.

• Consider other cardioversion strategies and alternative diagnoses if 3 doses of adenosine do not work.

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Executive Summary

Albumin is the most abundant protein in plasma (50%). It is produced by hepatocytes at a rate of 10-15 gr/day, with normal serum levels of 3.5-5 gr/dL.

• Function

  • Albumin is the primary component of intravascular oncotic pressure (80%).

  • It also plays a role in the transport of hormones and various molecules, acid-base balance among many other physiological functions.

• Usage

  • In the ED, albumin has several indications where proven benefits exist, such as decompensated chronic liver disease with spontaneous bacterial peritonitis, hepatorenal syndrome, and large-volume paracentesis.

  • In addition, it is the most commonly used colloid for volume replacement in circulatory failure (both as an adjunct and in refractory shock), with evidence suggesting that its use could be beneficial in certain conditions (sepsis, hypovolemia, major burns).

  • Hypoalbuminemia is associated with increased mortality, especially in critically ill patients. Nonetheless, routine replacement has not shown consistent benefits. Considering its high cost and potential risks, understanding its indications is crucial for appropriate use.

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Adult dose for large volume paracentesis in cirrhotic patients

• 8 gr of albumin every 1 liter of ascitic fluid evacuated, initiating albumin when more than 5 liters have been drained.

Notes:

• The purpose of albumin is to prevent Post Paracentesis Circulatory Dysfunction (PPCD).
• Example: when 5 liters have been evacuated, start an infusion of 40 gr of albumin, and add 8 gr for every additional liter drained.

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Executive Summary

Albuterol is a short-acting adrenergic β-2 receptor agonist (SABA), which is a fundamental treatment for bronchoconstriction crises typically caused by acute bronchitis, acute asthmatic exacerbations, and acutely decompensated COPD patients.

• Bronchodilators are indicated for symptomatic patients exhibiting signs and symptoms of airflow obstruction, such as wheezing, rhonchi, and prolonged expiration.

• For mild to moderate obstructive crises, aerosol-metered vs continuous nebulization show similar efficacy. However, for the severely distressed, continuous nebulization is advised for practical reasons.

• In the initial 4 hours of acute asthma exacerbation treatment, guidelines and experts do not stipulate a maximum prescribed dosage.

• Albuterol is also used as adjuvant therapy for moderate to severe hyperkalemia.

• Cautions: For most cases tachycardia is not a contraindication for using albuterol during a bronchoconstriction crisis, as it is usually well tolerated and self-limited.

  • Caution is advised in severe tachycardia; consider alternatives such as anticholinergic bronchodilators.

  • Avoid albuterol in moderate to severe hypokalemia.

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Adult dose for moderate to severe acute bronchoconstriction

• Nebulized: 2.5-5 mg every 20 minutes for the first hour.

• Metered-dose inhaler: 4-8 puffs every 20 minutes, repeated 3 times.

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Executive Summary

(Update with 2023 guidelines in progress)

Alteplase is a fibrin-specific Tissue Plasminogen Activator (tPA; fibrinolytic) that 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 for 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).

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Acute Coronary Syndrome with ST elevation (< 12 hours)

US-FDA approved

• Adult dose:
  • ≤ 67kg: 15mg bolus + 0.75 mg/kg in next 30 min
  • > 67kg: 15 mg bolus + 50 mg in 30 min + 35 mg in 60 min

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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 90 mg)
    • 10% bolus over 1 min
    • 90% infusion over 60 min
  • ≥ 100kg: 9 mg bolus + 81 mg 60 min

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Pulmonary Embolism

US-FDA approved.

• Adult dose:
  • Intermediate risk: 50 mg in 2 hrs
  • High risk: 100 mg in 2 hrs
  • Cardiac arrest: 50 mg bolus + 50 mg if no ROSC in 15 min

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Go to Fibrinolytics Table

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Executive Summary

Amiodarone is classified as a class III antiarrhythmic, affecting all phases of the action potential by inhibiting K+ efflux channels, Na+ channels, and L-type Ca2+ channels. Furthermore, it exhibits a non-competitive blockade action on beta receptors, resulting in a potent antiarrhythmic effect.

• Most ED use involves the treatment of ventricular and supraventricular arrhythmias. In-depth knowledge of these conditions and alternative effective treatments beyond amiodarone is necessary:

  • Cardiac arrest (VF and pulseless VT)
  • Ventricular tachycardia (VT)
  • Atrial fibrillation/flutter
  • Electrical storm

• Cautions summary:

  • Hypotension, bradydysrhythmias, and QT interval prolongation are the most common and relevant adverse reactions associated with acute use. Additionally, it has several long-term and chronic complications, including pulmonary, hepatic, thyroid and ocular issues.
  • It should not be used in patients with atrial fibrillation who have not been previously anticoagulated and in whom atrial thrombi have not been ruled out due to the risk of periprocedural cardioversion embolization and stroke, with a risk as high as 3-6%.

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Adult dose for cardiac arrest with shockable rhythms (VF and Pulseless VT (pVT))

It is only recommended in cases of persistent VF/pVT despite defibrillation attempts and the administration of epinephrine (see ACLS algorithm):

• Initial dose: 300 mg of amiodarone IV or IO for patients who remain in VF or pVT after three defibrillation attempts.
• Additional dose: 150 mg IV or IO if persistent VF/pVT after a total of five shocks.

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Adult dose for stable ventricular tachycardia

• Loading dose: 150 mg IV diluted in 100 ml 5% dextrose over 30 min.
• Continuous infusion: after loading dose, initiate infusion of 1 mg/min for 6 hr, then 0.5 mg/min for 18 hr.
• After initial IV administration, consider initiation of 400 mg every 8-12 hours for 1-2 weeks, then 300–400 mg daily; reduce dose to 200 mg daily if possible.
• Consider procainamide as the first-line antiarrhythmic for monomorphic VT.

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Executive Summary

Acetylsalicylic acid (ASA), also known as aspirin, is an NSAID with analgesic and anti-inflammatory effects that inhibit platelet aggregation. It is frequently prescribed in EDs worldwide as part of the standard treatment for acute coronary syndromes and other acute vascular conditions.

• To date, ASA is not commonly utilized as an analgesic or anti-inflammatory agent. Other NSAID alternatives, such as ibuprofen, exhibit significantly lower effects on platelet anti-aggregation and pose a lower risk of bleeding. An exception is observed in patients with coronary artery disease experiencing acute pericarditis.

• Cautions:

  • Increased risk of bleeding, kidney injury and peptic ulcer disease.
  • Adverse effects usually manifest at analgesic doses (300-600 mg every 4-6 hours), and rarely at lower antiaggregatory doses (≈100 mg/day).

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Adult dose for acute coronary syndromes

• Loading dose: 162 to 325 mg PO.

• Maintenance dose (beginning on the next day): 75 to 100 mg/day PO.

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Adult dose for acute ischemic stroke, transient ischemic attack

• Cautions:

  • Delay antiplatelet therapy for at least 24 hours in patients who have undergone IV fibrinolysis (alteplase or tenecteplase) and have had a control CT scan to rule out hemorrhagic conversion. Standard of care should involve consulting a vascular neurologist to guide treatment.

  • When hemorrhagic stroke has been ruled out in patients not eligible for fibrinolytic therapy, initiate aspirin therapy as soon as possible.

• First dose: 160 to 300 mg PO.

• Maintenance dose: 75-100 mg/day PO.

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Executive Summary

Atropine is a competitive antagonist of peripheral and central muscarinic receptors, with no effect on nicotinic receptors. In emergency medicine, it is commonly indicated for the initial management of symptomatic bradyarrhythmias and to counteract cholinergic symptoms such as respiratory secretions and bronchospasm in the case of muscarinic toxicity (cholinergic toxidrome).

• Cautions:
  • Consider critical and reversible bradycardia differentials, especially in the unstable patient (hypoxemia, electrolyte disturbances, ischemia).
  • There are no absolute contraindications to atropine. Relative contraindications are COPD or asthma, acute glaucoma, coronary heart disease, obstructive uropathy, bowel obstruction and myasthenia gravis. Use with caution.

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Adult dose for the treatment of symptomatic sinus bradycardia or AV block

• 0.5-1 mg IV, repeated every 3-5 min to a maximum of 3 mg.

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Executive Summary

Calcium gluconate is the calcium salt of gluconic acid. It is used intravenously to rapidly increase the blood calcium levels, as it plays a crucial role in various physiological processes such as heart function and nerve impulse conduction.

• In the ED, calcium gluconate is mainly used for the acute management of symptomatic severe hypocalcemia and in patients with severe hyperkalemia, as both of these conditions carry a high risk of arrhythmias.

• Cautions: contraindicated in hypercalcemia. Caution in hyperphosphatemia. May increase digoxin toxicity.

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Adult dose for acute severe hypocalcemia

• 1-2 gr IV over 10 min, may be repeated every 10-60 min if necessary.

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Adult dose for severe/emergent hyperkalemia

• 1-2 gr IV over 2-5 min, may be repeated every 15-30 min if needed (persistent EKG signs of hyperkalemia, AV blockade, etc).

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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. In an analysis of a large number of cyclobenzaprine overdoses, there were no reports of widened QRS, ventricular arrhythmias, or seizures.

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Adult dose for acute painful musculoskeletal spasms

Immediate release formulation*

• 5 mg TID with one dose at night.

• Maximum 30 mg/day, up to 2-3 weeks.

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

Dobutamine, a synthetic catecholamine, is one of the most studied and used inotropic agents in cardiovascular critical care for the treatment of cardiogenic shock (CS), with approval of the US-FDA for that condition.

• USA and European guidelines recommend norepinephrine as first-line vasopressor to manage hypotension in CS. Subsequently, if needed, an inotrope and/or mechanical cardiovascular support (MCS) may be added to improve perfusion and facilitate definitive intervention.

• It has inodilator properties as a beta-receptors agonist (𝛽1 and 𝛽2), with subsequent positive chronotropism, inotropism and mild peripheral vasodilation. This may provoke myocardial ischemia, arrhythmias and severe cardiovascular events. Use with extreme caution.

• Dobutamine is preferred over epinephrine for CS, as the latter is associated with an increased risk of refractory shock, lactic acidosis and mortality.

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Adult dose for cardiogenic shock:

• 2-20 ug/kg/min

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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.
  • Droperidol or olanzapine are considered first-line medications to treat acute severe agitation in psychiatric patients, and both can be used in combination with benzodiazepines.

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Adult dose for undifferentiated agitation in the ED

• 5-10 mg IM

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

• 1.25-2.5 mg IV or IM

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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 𝛽-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

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Adult dose for anaphylaxis

• 0.01 mg/kg (max 0.5 mg 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.

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Adult dose for cardiac arrest

• 1 mg 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 (with the exception of chest compressions while preparing defibrillation).

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Executive Summary

Racepinephrine is a mixture of epinephrine's L- and D- isomers. It is used nebulized as an effective and safe treatment for croup (acute laryngotracheitis) in pediatric patients, acting as a local vasoconstrictor to alleviate swelling and edema.

• While L-epinephrine has been proven safe and effective when administered via nebulization for croup, racepinephrine is considered by many experts and institutions as the first-line inhaled vasoconstrictor agent for the treatment of moderate to severe croup.

• Comparing racepinephrine with L-epinephrine, evidence has shown that there is no difference in croup score after 30 minutes of treatment. On the contrary, a better outcome has been observed after 120 minutes, favoring L-epinephrine.

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Pediatric dose for moderate to severe croup (acute laryngotracheitis)

• Nebulization of 0.05 ml/kg per dose (max 0.5 ml), diluted to 3 ml with normal saline.
  • Same dose may be repeated every 15 to 20 minutes as needed.

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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.

• 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 continuous infusion– but to minimize adrenal suppression.

Pharmacology for a single bolus administration

Onset	15-45 sec
Time to Peak Effect	45 sec
Duration of hypnotic effect	3-12 min

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Adult dose for rapid sequence intubation

• 0.3 mg/kg IV (total body weight).
  • Consider a lower dose of 0.2 mg/kg in profound shock.

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Executive Summary

Fentanyl is a potent opioid pain medication that is extensively used in the ED to manage severe acute pain and as premedication to intubation preparation.

• In the ED is usually preferred over other opioids (eg. morphine) due to its higher potency, faster onset of action, and shorter duration of action. This makes it useful to precisely titrate dosing in the acute setting. Additionally, it has a safer hemodynamic profile than morphine, causing less hypotension or cardiac instability.

• Cautions summary:

  • High risk of respiratory depression (black box warning) and other adverse effects; it should be used with caution, monitoring closely for respiratory depression, hypotension, sedation and other adverse effects.
  • High risk of addiction and overdose (black box warning): Its use should be limited to the management of short-term acute pain and critical care support.

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Adult dose for moderate to severe pain:

• 1 μg/kg/dose (usually 50-100 μg) IV.

  • Repeat in 1 to 2 hours as needed (label recommendation).

  • Consider repeat doses in 5-10 min in cases of excruciating pain (emergency medicine practice).

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Executive Summary

Flavoxate is a synthetic anticholinergic with urinary tract spasmolytic activity that is used for symptomatic alleviation in genitourinary conditions such as lower urinary tract infection, prostatitis, and urethritis.

• It does not have antibiotic properties, and should never be used as a replacement for appropriate antimicrobials.

• It should not be prescribed to patients with an increased risk of intestinal obstruction, ileus, or urinary retention, or any other conditions that may be aggravated by anticholinergic agents.

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Adult dose for symptomatic relief of urinary urgency, suprapubic pain secondary to UTIs

• 100-200 mg every 6 to 8 hours PO

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Executive Summary

Unfractionated heparin (UFH) is an endogenous anticoagulant that enhances antithrombin, ultimately preventing the conversion of fibrinogen to fibrin. It can be reversed by protamine.

• UFH and other anticoagulants are extensively used in the ED for many thrombotic-related events, such as venous thromboembolism (VTE) – including acute pulmonary embolism (PE) and deep venous thrombosis (DVT) – acute coronary syndrome, acute limb ischemia, mesenteric thrombosis, etc.
• There has been a clear tendency to replace UFH with low molecular weight heparins (LMWH) due to their predictable effects, easier administration, and monitoring advantages.
• Preference of UFH over LMWH:
  • High-risk pulmonary embolism.
  • Myocardial infarction with ST segment elevation.
  • Severely impaired renal function.
• Caution: Always evaluate the hemorrhagic risk before initiating anticoagulant therapy.

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Adult dose for pulmonary embolism

• 80 IU/kg bolus IV followed by a 18 IU/kg/hr infusion.

• UFH is preferred over LMWH for high-risk PE. For low and intermediate-risk PE, consider LMWH or oral anticoagulation alternatives.

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Adult dose for ST-segment elevation myocardial infarction (STEMI)

• Primary PCI*

  • 70 IU/kg bolus IV (max 5000 IU).
  • Routine post-procedural anticoagulant therapy is not indicated after primary PCI, unless there is a separate indication for its use.

• Fibrinolysis
  The 2017 ESC guidelines recommend anticoagulation with enoxaparin over UFH to patients eligible to fibrinolytic therapy. If UFH is selected:

  • 60 IU/kg bolus IV (max 4000 IU) followed by 12 IU/kg/hr infusion (max 1000 IU/hr)
  • Continue anticoagulation until PCI has been performed.

*PCI: Percutaneous coronary intervention
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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.

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Adult dose for acute intracranial hypertension caused by TBI

• NaCl 3%, 2 ml/kg IV over 15 minutes

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Executive Summary

Ibuprofen is the most extensively studied NSAIDs for the treatment of acute pain and is prescribed worldwide in EDs for both pediatric and adult patients.

• It is the only intravenous NSAID approved by the US-FDA for the treatment of both fever and pain (while other IV NSAIDs are approved solely for pain management). IV ibuprofen has the disadvantage of requiring a slow 30-min infusion.

• Pediatrics: with acetaminophen, it is considered a first-line analgesic for this population.

  • The US-FDA has approved the use of intravenous ibuprofen starting at the age of 3 months and oral formulations starting from 6 months of age.

• Cautions:

  • Usual NSAIDS adverse effects: cardiovascular thrombotic events, gastrointestinal bleeding (ulceration, perforation), heart failure, renal toxicity, etc.

  • Fetal toxicity: premature closure of fetal ductus arteriosus, neonatal renal impairment (avoid in pregnancy).

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Adult dose for pain or fever

• 400-800 mg IV or PO over 30 min every 6-8 hours as needed (maximum 3200 mg/day).

  • When given IV it should be infused over 30 min.

  • Individual doses of 400 mg and a cumulative daily dose of 1200-2400 may be the analgesic ceiling for acute pain management.

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Executive Summary

Ketamine, a dissociative and analgesic agent, has seen a notable surge in its usage within the ED over the past decade. It is employed as an induction agent for endotracheal intubation, procedural analgosedation, management of agitation, and acute pain relief.

• Ketamine may be considered as an alternative to etomidate as an induction agent for hemodynamically unstable patients, but it is associated with a higher incidence of peri-intubation hypotension compared to etomidate.

• Low-dose ketamine (0.2-0.5 mg/kg IV) has been found to be equally effective as morphine in the management of acute pain within the ED, demonstrating comparable safety profiles.

• A thorough understanding of ketamine's pharmacological properties and potential adverse effects is essential for its appropriate usage. Continuous monitoring is imperative during its administration.

• Cautions: respiratory depression, neuropsychiatric symptoms, hypertension and tachycardia, hypotension, laryngospasm, and potential dependence with prolonged use.

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Adult dose for endotracheal intubation induction

• 1.5-2 mg/kg IV.

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Adult dose for procedural sedation and analgesia

• 0.3-1 mg/kg IV.

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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.

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Adult dose for acute moderate to severe pain

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

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

*adults ≥65 years: max 60 mg/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.

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Adult dose for status epilepticus

• Loading dose of 60 mg/kg IV (max 4500mg) in 15 min.

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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

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Adult dose for local anesthesia

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

• Dosing calculator: MDCalc® - Local Anesthetic Dosing Calculator

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Adult dose for ventricular tachycardia

• 1-1.5 mg/kg IV.

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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).

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Adult dose for Local Anesthetic Systemic Toxicity (LAST)

• Intralipid® 20%, 1.5 ml/kg IV bolus over 1 minute (approximately 100 ml in adults), followed by an infusion of 0.25 ml/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.

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Sedation timing with single 2-4 mg dose:

Intravenous

Onset (IV)	5-10 min (shorter to terminate seizures)
Peak Effect (IV)	30 min
Duration (IV)	2-6 hrs

Intramuscular

Onset (IM)	15 min
Peak Effect (IM)	60 min
Duration (IM)	6-8 hrs

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Adult dose for seizures / status epilepticus

• 0.1 mg/kg IV (max 4 mg/dose).

• Repeat every 5-10 min until the crisis has ceased.

• Consider initiating an antiepileptic drug if a second lorazepam dose is required.

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Executive Summary

Magnesium sulfate (MgSO₄) is an essential inorganic salt used for a variety of conditions in the ED.

• Its most proven efficacy and benefit are observed in the treatment of hypertensive emergencies during pregnancy. Included on the World Health Organization's list of essential medicines.

• Established component for the management of Torsades de Pointes (subtype of polymorphic ventricular tachycardia).

• Adjuvant treatment in selected cases of acute exacerbated asthma and COPD, acute rate control of atrial fibrillation, and migraine. Caution is advised for those indications.

• Cautions

  • Increased risk of hypotension in rapid administration.

  • Continuous infusion, particularly in pregnant patients, requires vigilant oversight for potential hypermagnesemia toxicity and fetal distress. Crucial aspects include fetal monitoring and recognizing maternal signs such as hypotension, loss of deep tendon reflexes, altered mental status, and respiratory depression. This vigilance is essential to ensure the safe use of MgSO4 in the ED.

  • Despite the association of prolonged use with newborn bone abnormalities, short-term infusions for pregnancy hypertension emergencies are deemed safe and constitute a standard of care. Emergency clinicians should be familiar with treatment initiation, and immediate OB/GYN consultation is crucial for management guidance.

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Dose for seizure prevention and control in severe preeclampsia and eclampsia (hypertensive emergencies of pregnancy)

• 4-6 gr IV over 20-30 min, followed by an infusion of 1-2 gr/hr.

  • Eclampsia: if seizures recur during the infusion administration, an additional 2-4 gr may be administered IV over 5 min.

  • Consider labetalol or other antihypertensive agents for severe hypertension despite MgSO4 treatment.

  • Immediate OB/GYN consultation is strongly recommended.

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Executive Summary

Naloxone is an opioid receptor antagonist extensively used in prehospital settings and EDs to reverse respiratory depression and coma in opioid-intoxicated patients.

• An intranasal spray formulation is also available for domestic and bystander administration, aimed at reducing preventable deaths associated with the ongoing public health issue of opioid abuse.

• Cautions: a "standard dose" may induce severe withdrawal symptoms in opioid-dependent patients, especially during IV administration. A lower dosing approach is recommended if opioid-dependence is suspected.

• In the ED, it is crucial to prioritize the effective evaluation, assessment, and treatment of patients with coma and/or respiratory depression. Critical, time-dependent differentials include shock states, neurological disorders, toxic-metabolic conditions, and more. Proficiency in airway management is indispensable.

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Adult dose for opioid overdose

Non-opioid-dependent patients

• 0.4 mg IV every 2 to 3 minutes until adequate spontaneous ventilation is achieved, up to a maximum of 10 mg.

• If the patient requires more than one dose or is at risk of further episodes of respiratory depression, a continuous infusion should be considered, or repeat doses every 1 to 2 hours.

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Opioid-dependent patients

• 0.04 mg IV every 3 to 5 minutes until adequate spontaneous ventilation is achieved, up to a maximum of 2 mg.

• A significantly lower dose of naloxone should be considered to reverse hypoventilation and avoid withdrawal syndrome.

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Executive Summary

Nitroglycerin (NTG) is a nitrate prodrug of nitric oxide (NO), which primarily produces vasodilation as its main cardiovascular effect.

• It is used sublingually and intravenously to treat angina pectoris secondary to coronary artery disease. In the ED, it is commonly indicated in hypertensive emergencies, particularly acute cardiogenic pulmonary edema (ACPE) and acute coronary syndromes.

• NTG use in ACPE is associated with a shorter hospital length of stay, lower intubation rates, and decreased ICU admissions.

• Vasodilatory effects: venous > arterial. Arterial vasodilation and afterload reduction are correlated with higher doses.

• Cautions

  • NTG may cause severe hypotension.
  • Contraindicated if the patient has used PDE-5 inhibitors (eg. sildenafil) within the previous 48 hours.

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Adult dose for acute cardiogenic pulmonary edema

Only consider NTG in hypertensive acute heart failure.

• Intravenous:
  • Start IV infusion at 0.5-0.7 μg/kg/min (approx. 30-50 μg/min for an adult) and titrate every 3-5 min with increases of 20-50 μg/min. Max dose of 400 μg/min.

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Executive Summary

Norepinephrine (NE) is an endogenous catecholamine that plays a prominent role in the management of circulatory failure in the emergency department and critically ill patients.

• It is extensively used for hemodynamic support, frequently as a first-line vasopressor, with the exception of anaphylaxis epinephrine.
• Consider using norepinephrine in combination with inodilator agents in cases of cardiogenic shock.

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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 (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. It is of great importance to be familiarized with the available therapeutic arsenal for agitation, such as droperidol, benzodiazepines, ketamine, etc.

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Adult dose for severe agitation:

• 5 to 10 mg IM, repeated every 20 min if necessary
  • Maximum of 30 mg/day for intramuscular administration.

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Executive Summary

Omeprazole is the most prescribed proton pump inhibitor (PPI) worldwide. It reduces gastric acid secretion by irreversibly blocking the H⁺ / K⁺ ATPase enzyme within the gastric parietal cells.

• Globally, PPIs are commonly prescribed and administered in the ED for a variety of conditions, but there is no need to initiate PPI therapy within the first hours of emergency care, and no benefit has been proven in providing acute symptomatic relief in the ED.

• The acute management of upper gastrointestinal bleeding in the ED typically involves the empiric administration of an IV PPI bolus. However, the benefits of emergent administration are questionable, as it does not reduce mortality, rebleeding, use of hemoderivatives, or need for surgery. On the other hand, it has been associated with a reduced incidence of high-risk stigmata of hemorrhage.

• Resuscitation and bleeding control of hemorrhagic shock should be prioritized, and the administration of omeprazole should not delay upper endoscopy or standard management for severe hemorrhage (eg., administration of hemoderivatives).

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Adult dose for peptic ulcer bleeding

• 80 mg IV, followed by 40 mg every 6 hours IV.

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Executive Summary

Ondansetron is a selective serotonin receptor antagonist (5HT-3) with proven antiemetic properties, used in both children and adults to treat nausea and vomiting caused by a variety of conditions; such as chemotherapy, gastroenteritis, migraine, traumatic brain injury, etc.

• Its use in the ED has increased significantly in the past decade, due to its effectiveness and fewer adverse effects than other antiemetic drugs.

• When using multiple doses of ondansetron, a major concern is the risk of QT interval prolongation and subsequent potential arrhythmia. Patients with a history of prolonged QT interval or those at risk for it should be closely monitored.

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Adult dose for nausea and/or vomiting

• 4 to 8 mg PO or IV.
  • Repeat every 4 to 8 hours if necessary.
  • A maximum cumulative daily dose of 24mg may be a conservative approach for ensuring safety.

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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.

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Adult dose for vasopressor extravasation

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

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Executive Summary

Propofol is a hypnotic agent that enhances the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain through NMDA and GABA-A receptors, resulting in sedation and unconsciousness. Third most commonly used induction agent in the ED, following etomidate and ketamine. It has a fast onset of action and an extremely short half-life, which makes it suitable for various situations in the ED, particularly for patients requiring short-term sedation. * Propofol may be considered as a first-line induction agent for status epilepticus.

⚠ Cautions summary

• Circulatory, CNS and respiratory depression: reduction in blood pressure due to vasodilation and direct myocardial depression mandates extremely cautious use in unstable patients. Etomidate or ketamine are often preferred for hemodynamically unstable patients. High risk medication that should be used with extreme caution, especially when other CNS depressants are used concomitantly.

• Allergies: the manufacturer’s label contraindicates propofol in patients allergic to soybean or eggs. This concern has been discredited by multiple studies, experts, and societies in the fields of anesthesia, emergency medicine and immunology.

• PRIS (Propofol-Related Infusion Syndrome): propofol is formulated in an oil-in-water emulsion that can potentially lead to PRIS –characterized by acidosis, rhabdomyolysis, refractory bradycardia and eventually organ failures and death–. Prolonged and high-dose infusions pose a major risk.

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Adult dose for rapid sequence intubation (RSI)

• 1.5 mg/kg IV bolus.

Notes:

• Other induction agents, such as etomidate or ketamine, may be more appropriate for hemodynamically unstable and elderly patients. If propofol is selected, consider administering a reduced dose of 0.5-1 mg/kg.
• Onset of action: 15-45 sec.
• Duration of effect: 5-10 min.

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Executive Summary

Rabies immune globulin (RIG) consists of virus-neutralizing antibodies against the rabies virus, indicated for use alongside the rabies vaccine as post-exposure prophylaxis (PEP) in select cases. It provides passive immunity until endogenous antibody production begins.

• Highly effective in reducing mortality from confirmed exposures.
• Unnecessary if the exposed individual has received prior rabies vaccination.
• Must be administered as soon as possible within 7 days of the first rabies vaccine dose.
• ⚠ Cautions
  • RIG is generally considered safe. Severe adverse effects, such as anaphylaxis, are rare, while adverse reactions are usually mild and self-limited.
  • Overdosage may lead to partial suppression of antibody production; do not exceed the recommended dose.
  • RIG may carry a risk of transmitting infectious agents; however, this risk is minimized through stringent production standards.

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Adult dose for post-exposure prophylaxis (PEP)

• 20 IU/kg, single dose infiltration and/or IM injection (human-derived RIG).

  • Infiltrate the full dose of RIG thoroughly in the area around and into the wound(s), if anatomically feasible.
  • Inject the remainder, if any, intramuscularly at an anatomical site distant from the site of rabies vaccine administration (different muscle group). Preferably thigh or deltoid.

Notes:

• If using equine-derived RIG, administer a single dose of 40 IU/kg (instead of 20 IU/kg for human-derived RIG), following the same principles as for human RIG.
• Avoid infiltration of the gluteal muscles due to risk of sciatic nerve damage.
• Do not exceed the recommended dose of RIG, otherwise the active production of rabies antibodies may be particularly suppressed.

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Executive Summary

Rabies is a zoonotic disease caused by the rabies virus (RABV). It is one of the most lethal viral infections, with a mortality rate of nearly 100%.

• The rabies vaccine is remarkable, as its effectiveness approaches nearly 100% in preventing death after viral exposure. The high survival rate can also be attributed to the use of rabies immunoglobulin (RIG) in selected cases.

• >99% of global human deaths are attributed to exposure to infected dogs. Vaccination of pets and wildlife is an effective measure to reduce outbreaks.

• Knowledge of local epidemiological trends, animal bite protocols, and current rabies vaccination guidelines is crucial for appropriate rabies prevention.

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Adult and pediatric vaccination for Post-Exposure Prophylaxis (PEP)

Modified Essen Regimen

• 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

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Executive Summary

Rocuronium is becoming the most commonly used non-depolarizing neuromuscular blocking agent (N-NMBA) in the emergency department due to its ability to create excellent intubating conditions compared to other NMBAs, and its superior safety profile over succinylcholine for a variety of clinical conditions when the latter is contraindicated (NMBA table).

• Studies have shown that there are no significant differences in intubation conditions when using rocuronium at a dose ≥1.2 mg/kg compared to succinylcholine 1.5 mg/kg for RSI.

• Non-depolarizing NMBAs can be reversed with sugammadex at any point, or with neostigmine when significant recovery has been achieved (40% approx).

• In the ED, NMBA reversal is not an option in the vast majority of cases and is not included in most Emergency Medicine difficult airway algorithms.

Caution: contraindicated only in patients with a known allergy to rocuronium.

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Adult dose for rapid sequence intubation

• 1.5 mg/kg IV

  • Time to intubation level paralysis: 60 sec

  • Duration of paralysis: 40-60 min

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Executive Summary

Tenecteplase (TNK) is a modified form of the Tissue Plasminogen Activator alteplase, with enhanced fibrin affinity, diminished fibrinogenolysis (greater fibrin-specificity) and Plasminogen Activator Inhibitor-1 (PAI-1) resistance. These properties prolong its half-life permitting administration as a single bolus which is remarkably useful in emergency medicine.

• Myocardial infarction: fibrinolytic of preference for acute myocardial infarction with ST segment elevation within 12 hours of symptoms (preferably <4 hours) if time to percutaneous coronary intervention will exceed 120 minutes.

• Acute ischemic stroke: There is fast-growing evidence and experts recommendations to support its use as an alternative to alteplase.

• Cautions: fibrinolysis is a critical and high risk treatment that should not be taken lightly. This intervention must be decided -or at least supported- by a specialist (eg. emergency medicine, neurologist, cardiologist, intensivist).

  • Evaluate for individual risk of hemorrhage. Rule out relative and absolute contraindications with checklists (see contraindications).

• Learn more about fibrinolysis in Fibrinolytics Table and Alteplase.

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

Indicated when anticipated STEMI diagnosis to Percutaneous Coronary Intervention-mediated reperfusion time is >120 min and onset of MI is <12 hrs.

Intravenous, bolus

<60 kg	30 mg
60 to <70 kg	35 mg
70 to <80 kg	40 mg
80 to <90 kg	45 mg
≥90 kg	50 mg (max dose)

Note: reduce dose to half in patients ≥75 years of age.

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Adult dose for Acute Ischemic Stroke (AIS < 4.5 hrs)

Intravenous, bolus

• AIS eligible for mechanical thrombectomy

  • 0.25 mg/kg bolus (max 25 mg)

• AIS with minor neurological impairment uneligible for a mechanical thrombectomy

  • 0.25 mg/kg bolus (max 25 mg)
  • Higher doses NOT currently recommended

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Executive Summary

Terlipressin is a synthetic vasopressin receptor agonist that reduces portal pressure and has known benefits for treating certain complications of chronic liver disease.

• It has been used for decades in Europe and Latin America for the treatment of:

  • Upper gastrointestinal bleeding of variceal origin to improve survival and bleeding control.
  • Hepatorenal syndrome (HRS) to improve kidney function.

• In 2022, the US-FDA approved its use for HRS, positioning terlipressin as the first US-FDA-approved agent indicated to improve kidney function in adults with HRS.

• Cautions

  • As a vasopressor, it is associated with ischemic and cardiovascular events. Use with caution.
  • Black box warning: Terlipressin may cause serious or fatal respiratory failure. Patients with volume overload or with acute-on-chronic liver failure (ACLF) grade 3 are at increased risk.

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Adult dose for upper gastrointestinal bleeding (confirmed or suspected variceal origin)

• 2 mg every 4 hours IV during the first 48 hours, followed by 1 mg every 4 hours for a total of 3 to 5 days.

Note: at EMDrugs, we refer to the "terlipressin" dose in reference to "terlipressin acetate."
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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).

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Adult dose for tetanus treatment

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

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Adult dose for 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.

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Adult dose for WK treatment

• 500 mg IV every 8 hours for 3-5 days, then 250 mg IV daily for 3-5 days, then indefinitely daily PO supplementation
• Consider magnesium supplementation (2 gr 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.

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Adult dose for trauma with risk of significant hemorrhage

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

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