Intravenous atracurium besilate is indicated as an adjunct to general anesthesia during surgical procedures in order to relax the striated muscles and facilitate endotracheal intubation and ventilation. It is also indicated to facilitate assisted ventilation in intensive care unit

Adjuvant of general anesthesia

Atracurium should be administered intravenously only. Atracurium should not be used by intramuscular injection because it may cause tissue irritation and no clinical data exists regarding this route of administration

In order to avoid causing anxiety in the patient, atracurium should be administered only when the patient is unconscious. The injectable solution of atracurium besilate should not be mixed in the same syringe or administered simultaneously with the same needle, or alkaline solutions (eg, barbiturate solutions). >

As with all curares, monitoring of neuromuscular functions (monitoring) is recommended when using atracurium and atracurium in order to individually adjust the dosage.

Intubation

Initial bolus

An initial dose of atracurium atracurium of 0.3 to 0.6 mg / kg (depending on the duration of the desired curarization) administered as a bolus is recommended. It will provide sufficient relaxation for approximately 15 to 35 minutes.

Endotracheal intubation is usually possible 90 to 120 seconds after intravenous injection of 0.5 to 0.6 mg / kg A maximum neuromuscular block is usually obtained 3 to 5 minutes after administration. The spontaneous recovery time after completion of the complete block is about 35 minutes (recovery of 95% neuromuscular function from normal).
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Although the effect of atracurium is potentiated (approximately 35%) by anesthesia, with isoflurane or enflurane an identical initial dose of atracurium besilac (0.3-0, 6 mg / kg) may be administered for intubation provided its administration precedes that of these inhaled anesthetics. However, when the initial dose of atracurium is administered after a stable anesthesia with isoflurane or enflurane, the dose of atracurium should be reduced by one-third. A smaller reduction in the dose should be considered in the case of anesthesia, concomitant with halothane, in fact, halothane, and weakly increases the action of atracurium (approximately 20%).

Dose maintenance

Intermittent IV Injection: During prolonged surgical procedures, the neuromuscular block may be maintained by maintenance doses, from 0.1 to 0.2 mg / kg of atracurium besilac., Generally, The first dose is administered 20 to 45 minutes after the initial bolus and then at intervals of 15 to 25 minutes, but the administration of Doses, maintenance is determined by individual needs and patient response. The administration of successive additional doses does not lead to an increase in neuromuscular blockage.

Use in infusion: after an initial bolus of atracurium, the neuromuscular block may be maintained during prolonged surgical procedures by administration of atracurium as a continuous intravenous infusion of 0.3 to 0.6 mg / kg / H. The infusion should be started only after recovering spontaneously after the initial bolus

Solutions of atracurium butylate for infusion may be prepared by mixing the injectable solution of atracurium besilate with a suitable diluent (see below) to obtain a concentration of atracurium besilate Of 0.5 to 5 mg / ml.

During cardiopulmonary surgery with extracorporeal circulation, atracurium besilate may be administered as an infusion, using infusion rates, recommended. The hypothermia induced at 25-26 ° C reduces the rate of degradation of atracurium, therefore the complete neuromuscular block can be maintained by decreasing the infusion rate by about half.

Compatibility with perfusion liquids: the solution, injectable atracurium besylate diluted to 0.5 mg / ml with the following infusion fluids and stored at 30 ° C protected from light is stable during The times indicated below.

Infusion fluid

Stability time

Sodium Chloride 0.9% for Infusion, i.v.

24 hours

Glucose 5% for i.v. infusion

24 hours

Glucose 4% and sodium chloride 0.18% for i.v. infusion
24 hours

Ringer USP Solution

24 hours

Sodium lactate for i.v. infusion (Hartmann's solution)

4; hours

The inoculant solution of atracurium butilate diluted to 5 mg / ml with the following infusion fluids and stored at 30 ° C in the absence of light in 50 ml plastic syringes is stable during Times indicated below

Infusion fluid

Stability time

Sodium Chloride 0.9% for Infusion, i.v.

24 hours

Glucose 5% for i.v. infusion

24 hours

Glucose 4% and sodium chloride 0.18% for i.v. infusion
24 hours

Ringer USP Solution

24 hours

Sodium lactate for i.v. infusion (Hartmann's solution)

8; hours

Reversion of the block, neuromuscular

The atracurium-induced neuromuscular block may be lifted by the administration of an anticholinesterase such as neostigmine or pyridostigmine, generally associated with an atropine or glycopyrronium type anticholinergic in order to prevent the muscarinic adverse effects of; Anticholinesterase. Under balanced anesthesia, reversion can usually be considered about 20 to 35 minutes, after the initial dose of atracurium, or about 10 to 30 minutes after the last maintenance dose, when the recovery of muscle contraction, Begun. The complete reversion of the neuromuscular block is generally obtained from 8 to 10 minutes after administration of the agent by decubulating
Rare cases of difficulty, respiratory, probably due to reversion, incomplete, have been reported, after pharmacological reversion of the neuromuscular block induced by atracurium. As in the case of the other products of this class, the risk of residual neuromuscular block is increased when the block emergence is initiated at a deep block level or in case of insufficient doses of antagonist agents. >

Facilitation of ventilation, assisted in intensive care unit patients

After an initial bolus dose of 0.3 to 0.6 mg / kg, the neuromuscular block may be maintained by administration of atracurium besylate as a continuous infusion of 11 to 13 μg / kg / min (0.65 to 0 , 78 mg / kg / h). There is considerable individual variability and dosage may increase or decrease with time. Infusion rates as low as 4.5 μg / kg / min (0.27 mg / kg / h) or as high as 29.5 μg / kg / min (1.77 mg / kg / hr) are Needed in some patients

The rate of spontaneous recovery of the neuromuscular block after an infusion of atracurium besilate in a patient in ICU is independent of the duration of administration. >
The spontaneous recovery to a T4 / T1> 0.75 (proportion of the height of the fourth stimulation relative to the first in a train of four) occurs in approximately 60 minutes. A range of 32 to 108 minutes was observed during clinical trials.
Dosage Adjustments

Use in children: Dosage in children over one month is identical to that recommended in adults, in relation to body weight. Given the large individual variability of the neuromuscular response in children, neuromuscular monitoring is necessary.

Use in the newborn: use of atracurium is not recommended in newborns due to inadequate data available (see section 5.1 Pharmacodynamic properties)
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Use in the elderly: the dose, standard atracurium can be used in the subject, aged, however a slow injection is recommended.

Use in patients with renal and / or hepatic impairment: no change in dosage is necessary regardless of the degree of renal or hepatic insufficiency, even in the terminal stage.

Use in patients with cardiovascular disease: in severe cases the initial dose of atracurium should be administered in a slow injection of at least 60 seconds
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See also Warnings and Precautions,

Pharmacotherapeutic group: non-depolarizing neuromuscular blocking agent, ATC code, M03A C04.

Atracurium besilate is a non-depolarizing neuromuscular blocking agent (ATC code; M03A C04) which is administered intravenously to cause a relaxation of the striated muscles.
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The non-depolarizing neuromuscular blocking agents antagonize the action of the neurotransmitter acetylcholine by binding in a competitive manner to the cholinergic receptor sites, and on the motor plate of the neuromuscular junction these effects can be inhibited or neutralized by , Administration of anticholinesterases such as neostigmine or pyridostigmine.

As with other neuromuscular blocking agents, the time to onset of paralysis is reduced, and the duration of the maximum effect is prolonged with increasing doses of atracurium. >

Once the necromuscular blocking effect of atracurium is recovered more rapidly than in the case of tubocurarine, alcuronium and pancuronium, independent of the dose of atracurium, Of time that separates the onset of recovery (complete block) and complete recovery (measured by restoration of response, 95% tetanic to normal) is about 30 minutes under Anesthesia, balanced and 40 minutes under anesthesia, halothane, enflurane or isoflurane. Repeated doses have no cumulative effect on recovery rate.

For initial doses of atracurium butylate up to 0.5 mg / kg, histamine plasma levels increase by 15% in a dose-dependent manner, but hemodynamic changes remain minimal within this range; Of dosages. After administration of 0.6 mg / kg of atracurium besilate, histamine plasma levels increased by 92% and correlated with a transient decrease (5 minutes) in blood pressure and a brief episode (2 to 3 minutes) of redness of the skin. Although these effects have little clinical significance in most patients, attention must be paid to the risk of significant release of histamine at doses, recommended in susceptible individuals or in patients for whom a significant release of histamine , Would be particularly dangerous (eg patients with serious respiratory or cardiovascular disease).

Studies in susceptible pigs with malignant hyperthermia have shown that atracurium besilate does not trigger this syndrome The same finding has been made during clinical studies in patients with a history of acute, Malignant hyperthermia.

Atracurium besylate does not appear to modify intraocular pressure and is therefore a product suitable for ophthalmic surgery

Pediatric population

The limited literature data in the newborn suggest a variability in the action time and duration of action of atracurium in this population compared to children (see Dosage and Mode of Administration ).

It is not advisable to use a potentially hazardous machine or drive a vehicle within 24 hours of the complete disappearance of the atracurium curative action

Known or suspected hypersensitivity to the product

Atracurium besylate should be administered only by persons who are familiar with breathing techniques, artificial and subject to the availability of immediate intubation equipment, endotracheal breathing assistance, adequate oxygenation under positive pressure, and Elimination of CO2. The clinician must be ready to assist or control ventilation, and anticholinesterases must be available immediately for neuromuscular block reversion

Atracurium has no known effects on alertness, nociceptive threshold or thought. In surgery, it should be used only with adequate general anesthesia.

As with other curares, there may be a release of histamine in susceptible patients during the administration of atracurium besilate. Caution should be exercised in patients with a history of hypersensitivity to the effects of histamine.

Do not administer atracurium injectable intramuscularly.

Intravenous atracurium besilate has an acidic pH, therefore it should not be mixed with alkaline solutions (eg, barbiturate solutions) in the same syringe, nor should it be administered simultaneously through the Needle during intravenous infusion. Depending on the pH of such mixtures, inactivation of atracurium butylate could occur, with precipitation, of free acid.
When choosing a small-caliber vein, for injection, a physiological saline rinse should be done after the injection. In the case of administration of other anesthetics through the same indwelling needle or cannula, it is necessary to rinse each product with an adequate volume of physiological saline. >

Atracurium can produce significant effects in patients with myasthenia gravis, Lambert-Eaton syndrome or other neuromuscular diseases in which potentiation of non-depolarizing curares has been noted. It is particularly important in these patients to administer a reduced dose of atracurium and to use a peripheral stimulant to evaluate the neuromuscular block. The same precautions must be taken in patients with severe electrolyte abnormalities

At recommended doses, atracurium is devoid of significant vagolytic or gangliopelic properties. Therefore, it does not prevent bradycardia induced by many anesthetic agents or by vagal stimulation during interventions. Bradycardia under anesthesia may therefore be more frequent with atracurium than with other muscle relaxants.
As with other non-depolarizing curares, a lesser effect of atracurium may occur in burns. In this type of patient, an increase in the dose of atracurium may be necessary according to the time elapsed since the occurrence of the burn and the extent of it.

Atracurium besilate should be administered in a minimum of 60 seconds in patients with sensitivity unusual to hypotension, eg hypovolemic.
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Intravenous atracurium besideate is hypotonic and should not be perfused in the same tubulure as a blood transfusion.
Periodic monitoring of creatine phosphokinase (CPK) values ​​should be considered in asthmatic patients receiving high doses of corticosteroids and blockers, neuromuscular in the intensive care unit.
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Special precautions should be taken in cases of known history of anaphylactic reactions to curare, an allergic reaction which may occur with these agents. Code>
As for other non-depolarizing curares, the intensity and / or duration of atracurium effects can be increased, resulting from interaction with the following agents
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+ Inhalation anesthetics

Atracurium is potentiated by anesthesia with isoflurane, desflurane, sevoflurane, enflurane, and only marginally by halothane anesthesia.

+ Antibiotics

Aminosides, polymyxins, spectinomycin, tetracyclines, lincomycin, clindamycin and vancomycin.
+ Anti-convulsants (administration, single)

Pphenytoin, carbamazepine.

+ Anti-arrhythmics

Local anesthetics such as lidocaine, procainamide and quinidine.

+ Beta-blockers

Propranolol, oxprenolol.

+ Anti-rheumatic drugs

Chloroquine, d-penicillamine.

+ Calcium channel blockers

Diltiazem, nicardipine, nifedipine, verapamil.

+ Diuretics

Furosemide, thiazides, acetazolamide and potentially mannitol

+ Ganglioplegic

Trimétaphan, hexaméthonium.

+ Other

Dantrolene, parenteral magnesium sulfate, chlorpromazine, steroids, ketamine, lithium salts and quinine.

Rarely, some drugs mentioned above may aggravate or reveal a latent myasthenia, or even trigger a myasthenic syndrome. In these cases, increased sensitivity to atracurium is expected.

Administration of a combination of a non-depolarizing curare with atracurium may induce a degree of neuromuscular block greater than that which would normally result in a total equipotent dose of atracurium. The possible synergistic effect varies from one drug combination to the other.

A depolarizing muscle relaxant such as suxamethonium chloride should not be administered to prolong the neuromuscular block of a non-depolarizing curare such as atracurium as this may cause a complex block difficult to antagonize by anticholinesterases. Code>
Prior use of suxamethonium shortens the action time (up to maximum block) by approximately 2 to 3 minutes and may increase the depth of the neuromuscular block induced by atracurium. Therefore, the initial dose of atracurium should be reduced and should not be administered before the patient has recovered from neuromuscular blocking effects of suxamethonium. >
The concomitant use of intravenous corticosteroids and curares antagonizes the neuromuscular block. In addition, prolonged administration of this combination may increase the risk of myopathy and / or severity and, consequently, cause prolonged flaccid paralysis after cessation of curare. Myopathy is usually reversible with recovery in several months.

The appearance of the neuromuscular block may be delayed and its duration shortened in patients on long-term antiepileptic treatment (eg carbamazepine, phenytoin). However, if anti-convulsants are given in an isolated manner, the effects of the neuromuscular block may be increased.
Neuromuscular monitoring maintained until complete decararisation should in principle allow the detection of most interactions, but recourarization may occur in the case of postoperative antibiotic coverage, for example

The injectable solution of ATRACURIUM HOSPIRA has an acidic pH and can not be mixed in the same syringe with alkaline solutions (eg, barbiturates in solution) or administered as an intravenous infusion simultaneously with the same needle

The main signs of overdose are: prolonged muscular palsy and its consequences.

Data on atracurium overdosage after parenteral administration are limited. The risk of iatrogenic overdose can be minimized by careful monitoring of muscle contraction in response to peripheral stimulation. Excessive doses of atracurium may cause symptoms due to increased pharmacological effects. Overdosage may increase the risk of histamine release and undesirable cardiovascular effects, especially hypotension. If cardiovascular support therapy is needed, it should include proper patient positioning, water administration and the use of vasopressor treatments as needed .; It is essential to maintain free airways; Positive pressure until adequate spontaneous breathing is obtained. Total sedation is necessary, since atracurium does not alter vigilance. The duration of the neuromuscular block may be prolonged and nerve stimulation must be performed to monitor recovery. Recovery can be accelerated by the administration of an anticholinesterase such as neostigmine or pyridostigmine associated with an anticholinergic of the atropine type upon observation of the first signs of spontaneous recovery.

Pregnancy

Atracurium crosses the placental barrier, but no adverse effects have been demonstrated in the fetus or newborn. Studies in animals have not shown any adverse effects of atracurium on fetal development. As with all curares, the use of atracurium should be avoided during the first trimester of pregnancy, atracurium should not be used in the second and third trimesters unless it is absolutely necessary. Code>
Atracurium besilate may be used to maintain muscle relaxation during a caesarean section since at recommended doses it does not cross the placenta significantly. In an open study, atracurium besilate (0.3 mg / kg) was administered to 26 pregnant women during a caesarean section. Although small amounts of this drug have crossed the placenta, no harmful effects attributable to atracurarium have been observed in any of the newborns. The possibility of respiratory depression in the newborn should always be considered after a caesarean section in which a neuromuscular blocking agent has been administered.
Anesthesia during the third trimester of pregnancy exposes the mother to Mendelson syndrome (acid pneumonitis by gastric juice inhalation). If a muscle relaxant is used at the induction of anesthesia, a curare with brief action time, short duration of action and a small transplacental passage should be preferred and should be used at the most Low dose, necessary to achieve neuromuscular release; In patients receiving magnesium sulfate, reversion of the block may be unsatisfactory and the dose of atracurium should be reduced as indicated. >
Breastfeeding

Atracurium has a relatively high molecular weight and is highly ionized at physiological pH: these two factors greatly decrease the passage in milk. In addition, although milk is slightly more acidic than plasma, the atracurium present in the milk would be rapidly degraded. However, given the potential risk of respiratory depression in the newborn, particularly in premature infants, it is recommended to closely monitor the newborn when breastfeeding begins within 24 hours of administration Of atracurium.

The undesirable effects are listed in descending order, frequency within each system class, organ

As with most curares, there is a risk of undesirable effects suggestive of histamine release in susceptible subjects. In clinical trials (875 patients), skin rashes were reported within a range of 1% at doses up to 0.3 mg / kg and 29% at doses of 0.6 Mg / kg and above. The incidence of transient hypotension ranged from 1 to 14% for the corresponding dosages, respectively.
Table of adverse reactions by frequency of Atracurium Hospira 10 mg / ml solution, injectable
Classes of systems, organ

Very common

(≥ 1/10)

Common

(≥ 1/100 to;