Epinephrine, also called Adrenaline is a non-selective Beta and alpha receptor agonist. 

It causes vasoconstriction and bronchodilation.

Epinephrine Uses:

As a result, it is used to treat anaphylactic responses in which patients experience low blood pressure, skin rashes, wheezing, and shortness of breath.

Adrenaline/ epinephrine is also used in patients with:

• cardiac arrest, asystole,

• ventricular fibrillation or pulseless ventricular tachycardia unresponsive to initial defibrillation, and

• pulseless electrical activity.

It is utilised as an inotropic medication for bradycardia that is symptomatic and resistant to atropine as well as hypotension that is unresponsive to volume resuscitation.

It causes bronchodilation and is thus used to treat bronchospasm and viral croup.

To reduce the systemic absorption and lengthen the duration of action of local anaesthetics, it may be added.

It is occasionally injected at the site of bleeding as in variceal bleeding causing vasoconstriction and securing the bleeding site.

It is also used as a mydriatic agent during intraocular surgery.

Epinephrine uses in Emergency:

Epinephrine use in Anaphylaxis:

Anaphylaxis is a medical emergency.

Patients develop generalized body itching, urticaria, lips & facial swelling, difficulty in breathing, wheezing, and low blood pressure.

Anaphylaxis usually follows a bee sting, food allergens such as peanuts, fish, milk, and eggs, medicines like penicillin and sulfonamides, and vaccination.

If anaphylaxis is not treated promptly, it may result in death.

Epinephrine is a potent vasoconstrictor. It promptly relieves airway edema, itching, hypotension, and shock.

It is important to note that antihistamines and glucocorticoids only treat the cutaneous symptoms of anaphylaxis and have a delayed onset of action.

Once anaphylactic symptoms are identified, epinephrine should be given.

It needs to be injected intramuscularly (IM) in the middle of the outer thigh.

(Ref: Epinephrine for First-aid Management of Anaphylaxis)

EpiPens and Epinephrine autoinjectors in anaphylaxis:

The role of EpiPens and Epinephrine autoinjectors is increasingly being utilized for the early management of anaphylaxis.

Epinephrine autoinjectors should be used by the patients even in less severe cases (also termed as impending anaphylaxis).

Current guidelines recommend that patients who are at risk of anaphylaxis should carry at least two epinephrine autoinjectors because of the biphasic nature of the disease.

EpiPens and autoinjectors are costly but compared to treatment in the emergency visits and the risk of deaths, they may be cost-effective.

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Epinephrine in Asthma, angioedema, and allergic reactions:

Although safe alternatives such as albuterol, glucocorticoids, magnesium sulfate, and aminophylline now exist for the treatment of asthma, the role of epinephrine can never be underestimated.

Epinephrine can be used in patients with life-threatening asthma that does not get better with conventional treatment.

It acts as a bronchodilator and also relieves airway edema because of its alpha-agonist activity.

Epinephrine may be hazardous in elderly patients with atherosclerotic cardiovascular disease or several cardiac risk factors.

In severe asthma, the heart rate increases because of respiratory failure and hypoxemia.

Furthermore, in severe bronchospasm, inhalational therapies may not work.

One recently conducted study did not find any serious adverse effects such as arrhythmias, hypertension and myocardial infarction with the use of epinephrine in asthmatics.

Subcutaneous epinephrine may paradoxically decrease the heart rate.

This is because the patient can breath after the injection and the oxygenation saturations improve resulting in the normalization of heart rate.

In rare cases, it can also be administered as an intravenous infusion. It may be used as the last resort to avoid intubating the patient.

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Epinephrine in Cardiac Arrest:

Epinephrine is recommended by the AHA in patients with asystole and non-shockable rhythm.

After two unsuccessful defibrillations, it is also reasonable to use it on individuals who have a shockable rhythm.

When given within 20 minutes of an out-of-hospital cardiac arrest, it has also been demonstrated to increase patient survival.

A delay in the administration of epinephrine in patients with OHCC (Out of hospital cardiac arrest) was associated with worse neurological outcomes.

Similarly, patients who got epinephrine had much higher survival rates, but there was no significant difference in the rates of positive neurologic outcomes, according to researchers of the "A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest."

Epinephrine is ideally administered as an intravenous bolus in cardiac arrest, but intraosseous administration in pediatric patients was equally effective in one study.

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Epinephrine in Shock:

A low peripheral perfusion condition is shock. Cardiogenic, hypovolemic, neurogenic, or anaphylactic shock are all possible.

The initial treatment of most patients with shock is fluid resuscitation. Medicines used to treat shock include dopamine, dobutamine, norepinephrine, epinephrine, phenylephrine, and vasopressin.

Compared to dopamine, epinephrine was found to be more effective in one study in patients with fluid-refractory shock.

Epinephrine vs Norepinephrine in cardiogenic shock post-myocardial infarction:

In individuals with cardiogenic shock following myocardial infarction, epinephrine was found to be just as effective as nor-epinephrine at lowering arterial pressure and improving cardiac index.

In comparison to other vasopressors, epinephrine was also discovered to be linked to a three-fold increased risk of death in individuals with cardiogenic shock.

According to other research, individuals with nor-epinephrine-refractory shock may see higher hemodynamic improvements when given epinephrine sooner (within the first 24 hours of ICU admission).

However, its use was associated with a higher incidence of refractory shock.

Epinephrine Dose in Adults

Epinephrine dose for asystole/pulseless arrest, pulseless Ventricular tachycardia, and ventricular fibrillation:

Intravenous dose:

• Until the recovery of spontaneous circulation, 1 mg IV every 3 to 5 minutes;
• Higher doses of epinephrine up to 0.2 mg/kg may be used for the treatment of calcium channel blockers and beta-blocker overdose.

Endotracheal dose:

• Once intravenous or intraosseous access has been established or until the return of spontaneous circulation, 2-2.5 mg diluted in 5 to 10 ml of normal saline or distilled water (ideally distilled water) every 3 to 5 minutes should be administered.
• Alternative methods of endotracheal tube confirmation should be employed since endotracheal epinephrine may result in false-negative CO2 values.

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Adrenaline Dose in the treatment of bradycardia unresponsive to atropine: 

Intravenous infusion: 

• 2-10 mcg/minute or 0.1-0.5 mcg/kg/minute.

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Epinephrine dose in asthma:

Subcutaneous dose:

• 0.3-0.5 mg ( 1:1000 [1 mg/mL] solution) every 20 minutes for 3 doses

Nebulizer dose:

• When necessary, administer over a period of 15 minutes every 3–4 hours using a nebulizer and 0.5 mL (about 10 drops) of the mixture diluted with 3 mL of NS.

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Epinephrine dose in anaphylaxis and allergic reactions: 

Intramuscular injection in the anterior thigh is the preferred site for injection compared to the subcutaneous route.

Intramuscular and subcutaneous dose:

• Every 5–15 minutes, provide 0.2–0.5 mg (1:1000 [1 mg/mL] solution). The interval may be shortened in extreme circumstances.

Intravenous:

• Patients who are in refractory shock and in a cardiopulmonary arrest may be given intravenous injections of:

0.1 mg ( 1:10,000 [0.1 mg/mL] solution) over 5 minutes;

• Give intravenous infusions at 1-4 mcg/minute to patients in deep shock who are not responsive to volume resuscitation or those who need numerous epinephrine injections to avoid the need for repeated injections, or start with an infusion at 5-15 mcg/minute.

Epinephrine pen for Self-administration following severe allergic reactions (eg, insect stings, food): 

• The WHO suggests giving one dose for every 10–20 minutes spent travelling to a medical emergency centre.
• If more than two doses are necessary, they should be administered directly under the direction of a doctor.
• I.M., SubQ: 0.3 mg for Auvi-QTM, Epipen®, and Twinject®; repeat the dosage as necessary.

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Epinephrine injection for a severe and fluid resistant hypotensive shock:

Intravenous infusion: 

• 0.1-0.5 mcg/kg/minute

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Epinephrine dose for mydriasis during intraocular surgery: 

Intraocular dose:

• Before using a 1: 1000 (1 mg/mL) solution intravenously, dilute it to a concentration of 1:100,000 to 1: 1,000,000 (10 mcg/mL to 1 mcg/mL).
• Use as needed during the procedure as an irrigation solution, or inject a bolus dosage of 0.1 mL of a 1: 100,000 to 1: 400,000 (10 mcg/mL to 2.5 mcg/mL) dilution straight into the eye's anterior chamber.

Epinephrine dose in Children:

Epinephrine dose in Severe Asthma:

Note: Not advised for the regular management of asthma

Racemic epinephrine (2.25% solution):

• Children ≥4 years and Adolescents:

  • Use a nebulizer to administer 0.5 mL diluted with 3-5 mL of normal saline over a period of 15 minutes, as needed, every three to four hours.

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Epinephrine Dose in asystole or pulseless arrest:

Intravenous or intraosseous route:

• Maximum single dose: 1 mg; 0.01 mg/kg (0.1 mL/kg of 1:10,000 solution); every 3-5 minutes until return of spontaneous circulation

Endotracheal route:

• 0.1 mg/kg (0.1 mL/kg of a 1:1000 solution) every 3-5 minutes until spontaneous circulation returns or intravenous or intraosseous access is achieved (maximum single dose: 2.5 mg).

Note: Endotracheal administration may cause transient hypotension and reduce coronary perfusion

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Epinephrine dose in Bradycardia:

Intravenous or intraosseous:

• The maximum dosage is 1 mg or 10 mL, and it can be repeated every three to five minutes as necessary.

Endotracheal:

• Maximum single dose: 2.5 mg; doses as high as 0.2 mg/kg may be effective; repeat every 3-5 minutes as necessary until I.V./I.O. access is established; 0.1 mg/kg (0.1 mL/kg of 1:1000 solution);

Continuous infusion:

• I.V., I.O. : 0.1–1 mcg/kg/minute; titrate dose to desired outcome

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Epinephrine dose in Croup (laryngotracheobronchitis) and airway edema: 

Nebulization:

Racemic epinephrine (2.25% solution):

• every 20 minutes, 0.05–0.1 mL/kg (maximum dose: 0.5 mL) dissolved in 2 mL NS.

L-epinephrine:

• 0.5 mL/kg of a 1:1000 solution (maximum dose: 5 mL) diluted in NS, with the possibility of repeating the dose every 20 minutes.

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Epinephrine dose in Hypersensitivity reactions: 

Intramuscular is the preferred route as the subcutaneous route is less reliable and absorption may be slow. For self-administration, a single dose for every 20 minutes of travel time is recommended by the WHO.

Intramuscular and subcutaneous dose:

• 0.3-0.5 mg every 5–15 minutes, not to exceed 0.01 mg/kg (0.01 mL/kg/dose of 1:1000 solution).

Autoinjector dose:

• 10-25 kg: 0.15 mg Intramuscular in the mid-outer thigh
• >25 kg: 0.3 mg

Autoinjectors (EpiPen® Jr, EpiPen®, Twinject®):

• 15-29 kg: 0.15 mg; dose may be repeated in 5–15 minutes if allergic symptoms are still present.
• 30 kg: 0.3 mg; dose may be repeated in 5–15 minutes if allergic symptoms continue

Intravenous dose:

• To avoid numerous doses in more severe responses, continuous infusion (0.1 mcg/kg/minute) may be used instead of 0.01 mg/kg (0.1 mL/kg of 1:10,000 solution) every 20 minutes.

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Epinephrine dose in fluid resistant shock and hypotension

Continuous intravenous infusion:

• 0.1 to 1 mcg/kg/minute, with occasional use of up to 5 mcg/kg/minute

Subcutaneous administration:

• 3.dosages of 0.01 mg/kg (0.01 mL/kg of a 1:1000 solution) every 20 minutes (maximum of 0.5 mg in a single dose)

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Adrenaline as an Inotropic agent: 

Continuous infusion rate:

• 0.1-1 mcg/kg/minute

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Adrenaline dose in Postresuscitation infusion to maintain cardiac output or stabilize: 

Continuous infusion rate:

• 0.1-1 mcg/kg/minute;
• Effects on -adrenergic receptors are typically produced at doses less than 0.3 mcg/kg/minute. Alpha-adrenergic vasoconstriction is typically brought on by doses more than (>0.3 mcg/kg/minute).

Pregnancy Risk Factor: C

• Epinephrine passes the placenta and could result in anoxia in the foetus.
• Use during pregnancy only if the likelihood of the mother benefiting outweighs the likelihood that the foetus might be at risk.
• Unknown is the amount of excretion in breast milk. Breastfeeding mothers need to be cautious.

Dose in kidney impairment:

• No dosage adjustment provided in the manufacturer's labeling. 

Dose in Liver disease:

• No dosage adjustment provided in manufacturer's labeling. 

Adrenaline/ Epinephrine Side effects:

• Angina,
• angle-closure glaucoma,
• anorexia,
• anxiety,
• arrhythmias,
• cold extremities,
• confusion,
• difficulty in micturition,
• dizziness,
• dry mouth,
• dyspnoea,
• headache,
• hyperglycemia,
• hypersalivation,
• hypertension (risk of cerebral haemorrhage),
• hypokalemia,
• insomnia,
• metabolic acidosis,
• mydriasis,
• myocardial infarction,
• nausea,
• pallor,
• palpitation,
• psychosis,
• pulmonary edema (on excessive dosage or extreme sensitivity),
• restlessness,
• sweating,
• tachycardia,
• tissue necrosis at the injection site,
• tissue necrosis of the bowel,
• tissue necrosis of extremities,
• tissue necrosis of kidneys,
• tissue necrosis of the liver,
• tremor,
• urinary retention,
• vomiting, and
• weakness.

Epinephrine Contraindications

• Arteriosclerosis (in adults),
• arrhythmias,
• cerebrovascular disease,
• cor pulmonale,
• diabetes mellitus,
• elderly,
• hypercalcemia,
• hypertension,
• hyperthyroidism,
• hypokalaemia,
• ischaemic heart disease,
• obstructive cardiomyopathy,
• occlusive vascular disease,
• organic brain damage,
• phaeochromocytoma,
• prostate disorders,
• psychoneurosis,
• severe angina, and
• susceptibility to angle-closure glaucoma

Epinephrine (adrenaline) (systemic): Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use   

Risk Factor C (Monitor therapy).
Alpha1-Blockers	May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. In the same way, Alpha-/Beta Agonists could antagonize Alpha1Blocker vasodilation.
Antidiabetic Agents	Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
AtoMOXetine	Might increase the hypertensive effects of Sympathomimetics. AtoMOXetine could increase the tachycardic effects of Sympathomimetics.
Benperidol	Might reduce the therapeutic effects of EPINEPHrine Systemic.
Beta-Blockers (Beta1 selective)	Might reduce the therapeutic effects of EPINEPHrine Systemic.
Beta-Blockers (Nonselective).	May increase the hypertensive effects of EPINEPHrine Systemic. Arotinolol, Carvedilol, and Labetalol are exceptions.
Beta-Blockers (with Alpha-Blocking Properties	Might reduce the therapeutic effects of EPINEPHrine Systemic.
Cannabinoid-Containing Products	Sympathomimetics may increase the tachycardic effects of Sympathomimetics. Cannabidiol is an exception.
Chloroprocaine	May enhance the hypertensive effect of Alpha-/Beta-Agonists.
CloZAPine	May diminish the therapeutic effect of Alpha-/Beta-Agonists.
Inhibitors of COMT	Might decrease metabolism of COMT Substrates.
Doxofylline	Doxofylline may be more toxic or harmful if taken with Sympathomimetics.
Guanethidine	May increase the arrhythmogenic effects of Sympathomimetics. The hypertensive effects of Sympathomimetics may be enhanced by Guanethidine.
Monoamine Oxidase Inhibitors	Might increase the hypertensive effects of EPINEPHrine Systemic.
Solriamfetol	Sympathomimetics could increase the hypertensive effects of Solriamfetol.
Spironolactone	May diminish the vasoconstricting effect of Alpha-/Beta-Agonists.
Sympathomimetics	May increase the toxic/adverse effects of other Sympathomimetics.
Tedizolid	Might increase the hypertensive effects of Sympathomimetics. Tedizolid could increase the tachycardic effects of Sympathomimetics.
Risk Factor D (Regard therapy modification)
BenzylpenicilloylPolylysine	Alpha-/Beta-Agonists may diminish the diagnostic effect of BenzylpenicilloylPolylysine. Management: A histamine skin test may be used as a positive control in order to determine if a patient is able to mount a wheal or flare response.
Topical Cocaine	Sympathomimetics may increase hypertensive effects. Management: If possible, consider other options to this combination. Concurrent use of this combination can cause significant elevations in blood pressure and heart rate. You should also be aware of any signs of myocardial injury.
Hyaluronidase	May enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Management: Avoid the use of hyaluronidase to enhance dispersion or absorption of alpha-/beta-agonists. Clinically, it may be indicated to use hyaluronidase in patients who are receiving alpha/beta-agonists for other purposes.
Inhalational Anesthesia	Systemic may increase the arrhythmogenic effects of EPINEPHrine (Systemic). Patients who are currently receiving or have received inhalational anesthetics should be administered epinephrine with extra caution. Monitor for cardiac arrhythmias and use lower doses than usual.
Linezolid	Sympathomimetics may increase hypertensive effects. Patients receiving linezolid should be reduced in initial doses and closely monitored for an increased pressor response. There are no recommendations for dose adjustments.
Promethazine	This may reduce the vasoconstricting effects of EPINEPHrine Systemic. Management: If patients are experiencing vasoconstrictive effects from promethazine, there may be alternatives to epinephrine. When treating hypotension caused by promethazine overdose, you should consider using phenylephrine and norepinephrine.
Serotonin/Norepinephrine Reuptake Inhibitors	May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists.
Tricyclic Antidepressants	DirectActing may increase the vasopressor effects of Alpha/Beta-Agonists. Patients on tricyclic antidepressants should avoid direct-acting alpha/beta-agonists. Monitor for increased pressure effects when combined and reduce the initial doses of alpha/beta-agonists.
Risk Factor X (Avoid Combination)
Blonanserin	Might reduce the therapeutic effects of EPINEPHrine Systemic.
Bromperidol	Might reduce the therapeutic effects of EPINEPHrine Systemic.
Ergot Derivatives	May enhance the hypertensive effect of Alpha-/Beta-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. There are exceptions: Ergoloid Mesylates and Nicergoline.
Lurasidone	EPINEPHrine (Systemic), may increase the hypotensive effects of Lurasidone.

Monitor:

• Keep an eye on your heart rate, blood pressure, and extravasation at the infusion site.
• During continuous infusion, a cardiac monitor and blood pressure monitor are necessary.
• Determine the intravascular volume and provide support as necessary if using to treat hypotension.

How to administer Epinephrine:

• Central line administration via an infusion pump is preferred for intravenous infusions.
• You can inject epinephrine solutions intramuscularly, intraosseously, endotracheally, intravenously, or SubQ.
• Subcutaneous administration is less reliable and has slow absorption.
• For anaphylaxis, Intramuscular administration in the anterior thigh is the preferred site (avoid administration into the buttocks).
• In obese patients, administer into the lower thigh or even the calf muscles.

Endotracheal administration in cardiac arrest:

• In sterile water, dilute. Stop compressions and swiftly squirt the medication down the tube.
• Continue chest compressions and give numerous fast insufflations after that.
• With exhaled CO 2 detectors, endotracheal injection may result in false-negative readings.

Extravasation management:

• As a remedy, provide phentolamine. Combine 9 mL of NS with 5 milligrammes of phentolamine.
• This dilution should be injected sparingly into the extravasated region. Blanching should be stopped right away.
• site monitoring It could be necessary to administer more phentolamine injections if blanching should reoccur.

Usual Infusion Concentrations:

Adult I.V. infusion: 

• D5W or NS at concentrations of 1 mg per 250 mL (concentration: 4 mcg/mL) or 4 mg per 250 mL (concentration: 16 mcg/mL)

Pediatric I.V. infusion: 

• 16 mcg /mL, 32 mcg /mL, or 64 mcg /mL Incompatible in sodium bicarbonate.

Adrenaline/ Epinephrine Mechanism of Action :

• Epinephrine activates beta-adrenergic receptors, which relaxes and activates the smooth muscle of the bronchial tree, stimulates the heart, and dilates the skeletal muscles (in small doses).

Metabolism: The liver and adrenergic neuron via COMT or MAO metabolize these metabolites. 

Inactive metabolites are excreted from the urine. 

Epinephrine brands in US:

• Adrenalin
• Asthmanefrin
• Auvi-Q
• EpiPen 2-Pak
• EpiPen Jr 2-Pak
• S2
• Twinject

Epinephrine Brand Names: Canada

• Adrenalin
• Epi E-Z Pen
• EpiPen
• EpiPen Jr
• Twinject

Epinephrine brands in Pakistan:

ADECAINE WITH ADRENALINE  ( P.D.H. PHARMACEUTICALS (PVT) LTD )

 Injections : 2 ml :

Lignocaine : 20 mg/ml :

Adrenaline : 0.001%w/v :

100 injections pack : Rs.250

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ADRENALINE  (VENUS PHARMA)

 Injections : 1 mg/ml :

10 ml injection : Rs. 11.52

1 ml injection 100 injections per pack : Rs. 158.75

25 ml injection : Rs.21

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L-CAINE  (OPHTH-PHARMA (PVT) LTD)

 Lignocaine : 20 mg/ml :

 Adrenaline : 0.001%w/v :

10 ml injection 50 injections per pack : Rs.  950

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LIGNOCAIN (SHIFA LABORATORIES.(PVT) LTD )

Lignocaine : 2%w/v :

50 ml injection pack : Rs. 44

   Lignocaine : 20 mg/ml :

     Adrenaline : 0.001%w/v :

50 ml injection 10 injections per pack : Rs. 44

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LIGNOCAINE WITH ADRENALINE (LAHORE CHEMICAL & PHARMACEUTICALS WORK (PVT) LTD )

 Lignocaine : 20 mg/ml :

Adrenaline : 0.001 %w/v :

10 ml injection 50 injections per pack : Rs.0.00

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M B-CAIN (MULTINATIONAL BUISNESS LINK)

Lignocaine : 2%w/v :

10 ml injection 50 injections per pack : Rs. 600     Lignocaine : 20 mg/ml :

Adrenaline : 0.001 %w/v :

10 ml injection 50 injections per pack Rs. 650

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MEDICAINE  (HOSPITAL SUPPLY CORPORATTION)

Lignocaine : 20 mg/ml :

    Adrenaline : 0.001 %w/v :

1.8 ml injection 50 carts per pack : Rs. 676

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XYLEX-AD (VENUS PHARMA)

Lignocaine : 20 mg/ml :

  Adrenaline : 0.001 %w/v :

10 ml injection 50 injections per pack : Rs. 660

  Lignocaine : 20 mg/ml :

Adrenaline : 0.001 %w/v :

2 ml injection 100 injectiona per pack : Rs. 235.43 

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XYLOCAINE WITH ADRENALINE (BARRETT HODGSON PAKISTAN (PVT) LTD)  

    Lignocaine : 10 mcg/ml :

Adrenaline : 5mcg/ml :

10 ml injection 50 injections per pack : Rs. 810

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XYLODOS (DOSACO LABORATORIES)

Lignocaine : 20 mg/ml :

Adrenaline : 0.001%w/v :

2 ml injection : Rs. 3

Lignocaine : 2 %w/v :

50 ml injection : Rs. 0.00

    Lignocaine : 20 mg/ml :

  Adrenaline : 0.001 %w/v :

50 ml injection : Rs. 16

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XYLOX ADRENAUNE (VENUS PHARMA)

Lignocaine : 0 :

    Adrenaline : 0 :

50 ml injection : Rs. 11.76