Atracurium

Atracurium is a skeletal muscle relaxant belonging to non-depolarizing neuromuscular agent

Atracurium is used in the treatment of Mechanically ventilated patients during surgery and ICU, neuromuscular blockade.

Atracurium Crosses the placenta (small amounts). Volume of distribution: 120-188 mL/kg. Plasma protein binding: Approx 80% and get Converted to laudanosine and other metabolites by degradation via Hofmann elimination; undergoes ester hydrolysis by non-specific plasma esterases which gets excreted Via urine and bile, mostly as metabolites. Elimination half-life: Approx 20 min.

The onset of action of Atracurium was within 2-3 min

The Duration of action of Atracurium was about 15 minutes.

Atracurium is available in Solution.

The common side effects of Atracurium was Haemolytic anaemia, leucopenia, Nausea, vomiting, gastrointestinal distress.

Atracurium is available in India, Germany, Canada, France, USA

Atracurium is a non-depolarizing neuromuscular blocking drug of the benzylisoquinolinium class. It is a competitive antagonist of the alpha subunit of the postsynaptic nicotinic receptor at the neuromuscular junction. It competes with acetylcholine for binding sites. The binding of the postsynaptic nicotinic receptor by atracurium prevents depolarization of the motor endplate and subsequent skeletal muscle contraction. Unlike binding of depolarizing agents, binding of atracurium or other non-depolarizing agents does not induce a receptor conformational change.

Atracurium is available in the form of Solution.

Atracurium is used in the treatment of Mechanically ventilated patients during surgery and ICU, neuromuscular blockade.

Atracurium produces neuromuscular blockade by competing w/ acetylcholine for receptors on the motor end-plate of the myoneural junction.

Atracurium is approved for use in the following clinical indications

Mechanically ventilated patients during surgery, neuromuscular blockade: As an adjunct to general anesthesia, to facilitate endotracheal intubation, and to provide skeletal muscle relaxation during surgery.

Mechanically ventilated patients in the ICU, neuromuscular blockade: To facilitate endotracheal intubation and to provide skeletal muscle relaxation mechanical ventilation in ICU patients.

• Mechanically ventilated patients during surgery, neuromuscular blockade (adjunctive therapy):

Note: Inhaled anesthetic agents (eg, desflurane, isoflurane, enflurane, sevoflurane) prolong the duration of action of atracurium. Use lower end of the dosing range; redosing interval guided by monitoring with a peripheral nerve stimulator.

Initial: IV: Loading dose of 0.25 to 0.6 mg/kg .

Maintenance:

Intermittent dosing: IV: 0.08 to 0.1 mg/kg every ~15- to 25-minute intervals according to desired clinical response.

Continuous infusion: IV: Initial: 4 to 12 mcg/kg/minute; titrate based on response; usual dosage range: 2 to 15 mcg/kg/minute.

• Mechanically ventilated patients in the ICU, neuromuscular blockade:

Note: May use to facilitate mechanical ventilation (eg, moderate to severe acute respiratory distress syndrome [ARDS]), for refractory, life-threatening status asthmaticus, or for shivering from therapeutic hypothermia.

Continuous infusion: IV: Initial: Loading dose of 0.4 to 0.6 mg/kg, followed by continuous infusion of 4 to 12 mcg/kg/minute; adjust rate every ~10 minutes according to desired clinical response and/or peripheral nerve stimulation; usual dosage range: 2 to 20 mcg/kg/minute.

Atracurium is available in the dosage strength of 5 ml, 10 ml.

Atracurium is available in the form of Solution.

• Dosage Adjustment for Pediatric Patients:

Neuromuscular blockade:

ICU paralysis (eg, facilitate mechanical ventilation):

Infants, Children, and Adolescents:

Initial bolus: IV: 0.3 to 0.6 mg/kg/dose; repeat additional doses as needed to maintain desired neuromuscular blockade or begin continuous infusion.

Continuous IV infusion: Initial: 5 to 12 mcg/kg/minute (0.3 to 0.7 mg/kg/hour); range: 5 to 40 mcg/kg/minute (0.3 to 2.4 mg/kg/hour).

Adjunct to surgical anesthesia:

Bolus doses:

Infants and Children <2 years: Initial: IV: 0.3 to 0.4 mg/kg once, followed by additional doses as needed to maintain neuromuscular blockade.

Children ≥2 years and Adolescents: IV: 0.4 to 0.5 mg/kg once as initial dose, then administer 0.08 to 0.1 mg/kg/dose 20 to 45 minutes after the initial dose to maintain neuromuscular blockade; repeat dose every 15 to 25 minutes as needed. Note: Initial dose should be reduced to 0.3 to 0.4 mg/kg in patients with significant cardiovascular disease or with history of increased risk of histamine release (eg, asthma, severe anaphylactoid reaction).

Continuous IV infusion in operating room during extended surgical procedures:

Infants and Children <2 years: Continuous IV infusion: Initial: 6 to 14 mcg/kg/minute (0.4 to 0.8 mg/kg/hour) initiated at the first signs of recovery from initial bolus; titrate until desired neuromuscular blockade is achieved .

Children ≥2 years and Adolescents: Continuous IV infusion: Initial: 9 to 10 mcg/kg/minute (0.5 to 0.6 mg/kg/hour), initiate infusion at initial signs of recovery from bolus dose, titrate until desired neuromuscular blockade is achieved; block is usually maintained by a rate of 5 to 9 mcg/kg/minute (0.3 to 0.5 mg/kg/hour); range: 2 to 15 mcg/kg/minute (0.1 to 0.9 mg/kg/hour).

Atracurium is contraindicated in patients with:

Hypersensitivity to atracurium or any component of the formulation; known hypersensitivity to benzyl alcohol (multiple dose vials)

Documentation of allergenic cross-reactivity for neuromuscular blockers is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Concerns related to adverse effects:

• Anaphylaxis: Severe anaphylactic reactions have been reported with atracurium use; some life-threatening and fatal. Appropriate emergency treatment (including epinephrine 1 mg/mL) should be immediately available during use. Use caution in patients with previous anaphylactic reactions to other neuromuscular blocking agents.

• Bradycardia: May be more common with atracurium than with other neuromuscular-blocking agents since it has no clinically significant effects on heart rate to counteract the bradycardia produced by anesthetics.

• Prolonged paralysis: Some patients may experience prolonged recovery of neuromuscular function after administration (especially after prolonged use). Patients should be adequately recovered prior to extubation. Other factors associated with prolonged recovery should be considered (eg, corticosteroid use, patient condition).

Atracurium may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

Pregnancy Category C:

In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans, though.

• Common Adverse effects: Skin flush, erythema, pruritus, urticaria, wheezing, increased bronchial secretions

• Less Common Adverse effects: bronchospasm, cyanosis, angioedema, CV effects (e.g. bradycardia); wheals and erythema at inj site..

• Rare Adverse Effects: Anaphylaxis.

Enhanced neuromuscular blocking effect w/ general anesthesia (e.g. enflurane, isoflurane, halothane), certain antibiotics (e.g. aminoglycosides, polymyxins), lithium, Mg salts, procainamide, quinidine.

The common side effects of Atracurium include the following :

Skin flush, erythema, pruritus, urticaria, wheezing, increased bronchial secretions.

Symptoms: Stimulation of histamine release, CV effects esp hypotension.

Management: Supportive and symptomatic treatment. Maintain adequate, patent airway w/ manual or mechanical ventilation, as necessary. May administer neostigmine, edrophonium or pyridostigmine to reverse neuromuscular blockade. If CV support is needed, treatment should include proper positioning, fluid admin and use of vasopressors as necessary.

• Pharmacodynamics

Atracurium produces neuromuscular blockade by competing w/ acetylcholine for receptors on the motor end-plate of the myoneural junction.

• Pharmacokinetics

Distribution: Crosses the placenta (small amounts). Volume of distribution: 120-188 mL/kg. Plasma protein binding: Approx 80%.

Metabolism: Converted to laudanosine and other metabolites by degradation via Hofmann elimination; undergoes ester hydrolysis by non-specific plasma esterases.

Excretion: Via urine and bile, mostly as metabolites. Elimination half-life: Approx 20 min.

1. https://pubmed.ncbi.nlm.nih.gov/1091001/
2. https://clinicaltrials.gov/ct2/show/NCT01422915
3. https://clinicaltrials.gov/ct2/show/NCT02263547
4. https://www.medicines.org.uk/emc/product/128/smpc.