Tracrium

Generic Name: Atracurium Besylate
Class: Neuromuscular Blocking Agents
VA Class: MS200
Chemical Name: 2,2′- [1,5-Pentanediylbis [oxy(3-oxo-3,1-propanediyl)]]bis[1-[(3,4-dimethoxyphenyl)methyl] -1,2,3,4-tetrahydro-6,7-dimethoxy-2-methylisoquinolinium] dibenzenesulfonate
Molecular Formula: C65H82N2O18S2
CAS Number: 64228-81-5

Warning(s)

  • Should be administered only under supervision of qualified clinicians experienced in the administration of neuromuscular blocking agent therapy.1

Introduction

Nondepolarizing neuromuscular blocking agent.1

Uses for Tracrium

Skeletal Muscle Relaxation

Production of skeletal muscle relaxation during surgery after general anesthesia has been induced.1 2

Facilitation of endotracheal intubation;1 2 however, succinylcholine generally is preferred in emergency situations where rapid intubation is required.17 58 80 83 84 86 91 94 A single dose should not be used in place of succinylcholine for rapid sequence induction of anesthesia (“crash intubation”).2

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Treatment to increase pulmonary compliance during assisted or controlled respiration after general anesthesia has been induced.1 2

Has been used for facilitation of mechanical ventilation in intensive care settings.1 133 134 135 167

Tracrium Dosage and Administration

General

  • Adjust dosage carefully according to individual requirements and response.1

  • Assess neuromuscular blockade and recovery in patients undergoing anesthesia; a peripheral nerve stimulator is recommended to accurately monitor the degree of muscle relaxation and to minimize the possibility of overdosage.1

  • To avoid patient distress, administer only after unconsciousness has been induced.1

Facilitation of Endotracheal Intubation

  • Endotracheal intubation for nonemergency surgical procedures generally can be performed within 2–2.5 minutes following administration.1 2 (See Onset and also Duration under Pharmacokinetics.)

Maintenance of Neuromuscular Blockade

  • Repeated administration of maintenance doses does not have a cumulative effect on duration of neuromuscular blockade,1 2 9 24 42 43 provided recovery from blockade is allowed to begin prior to administering maintenance doses.1

  • Rate of spontaneous recovery from neuromuscular blockade following discontinuance of maintenance infusion usually is comparable to that following administration of a single IV injection.1 (See Onset and also Duration under Pharmacokinetics.)

Reversal of Neuromuscular Blockade

  • To reverse neuromuscular blockade, administer a cholinesterase inhibitor (e.g., neostigmine, pyridostigmine, edrophonium), usually in conjunction with an antimuscarinic (e.g., atropine, glycopyrrolate) to block adverse muscarinic effects of the cholinesterase inhibitor.1 9 16 17 18 19 21 23 24 26

  • Under balanced anesthesia, reversal generally can be attempted about 20–35 minutes after the initial dose or 10–30 minutes after the last maintenance dose, when recovery of muscle twitch has started.1

  • Complete reversal generally is achieved within 8–10 minutes after administration of the cholinesterase inhibitor and antimuscarinic.1

Administration

Administer IV only; do not administer IM.1 2

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer initial (intubating) dose by rapid IV injection;1 2 HID administer maintenance dosage for prolonged surgical procedures by intermittent IV injection1 2 or continuous IV infusion.1 3 57 60 90 118 119

Consult specialized references for specific procedures and techniques of administration.

Do not mix in the same syringe or administer through the same needle as an alkaline solution.1

Dilution

For continuous IV infusion, dilute atracurium besylate injection to the desired concentration (usually 0.2 or 0.5 mg/mL) in 5% dextrose, 5% dextrose and 0.9% sodium chloride, or 0.9% sodium chloride injection.1 Use within 24 hours.1

Dosage

Available as atracuium besylate; dosage expressed in terms of the salt.1

Pediatric Patients

Skeletal Muscle Relaxation
Initial (Intubating) Dosage
IV

Infants and children 1 month to 2 years of age: 0.3–0.4 mg/kg when used concomitantly with halothane anesthesia.1 132 169 170 171 (See Onset and also Duration under Pharmacokinetics.)

Children >2 years of age should receive dosages recommended for adults.1 (See Adults under Dosage and Administration.)

Insufficient data for recommendation of a specific initial dose of atracurium besylate in infants and children following administration of succinylcholine.132

Maintenance Dosage
Intermittent IV Injection

Infants and children may require more frequent doses than adults.1 2 132

Children >2 years of age should receive doses recommended for adults.1 (See Adults under Dosage and Administration.)

Continuous IV Infusion

Not recommended in children <2 years of age.1 169 170 171

Children >2 years of age should receive dosages recommended for adults.1 (See Adults under Dosage and Administration.)

Adults

Skeletal Muscle Relaxation
Initial (Intubating) Dosage
IV

0.4–0.5 mg/kg.1 2 (See Onset and also Duration under Pharmacokinetics.)

Reduce initial dosage by about 33% (i.e., to 0.25–0.35 mg/kg) if steady-state anesthesia has been induced with enflurane or isoflurane.1 2 37 169 170 171 (See Specific Drugs under Interactions.)

Consider reducing initial dosage by about 20% if steady-state anesthesia has been induced with halothane.1 2 86 (See Specific Drugs under Interactions.)

If administering following succinylcholine, reduce dosage to 0.3–0.4 mg/kg.1 2 86 Reduce dosage further (e.g., to 0.2–0.3 mg/kg) when inhalation anesthetics are also administered concomitantly.1 2 86 (See Specific Drugs under Interactions.)

Maintenance Dosage
Intermittent IV Injection

0.08–0.1 mg/kg, administered as necessary.1 2 (See Onset and also Duration under Pharmacokinetics.)

Administer first maintenance dose generally 20–45 minutes after the initial dose in patients undergoing balanced anesthesia.1 2

Administer repeat maintenance doses at relatively regular intervals (i.e., from 15–25 minutes in patients undergoing balanced anesthesia).1 2 Administration at longer intervals may be possible if higher maintenance doses (i.e., up to 0.2 mg/kg) are used or if used with enflurane or isoflurane.1 2

Continuous IV Infusion

Initially, 9–10 mcg/kg per minute may be necessary to rapidly counteract spontaneous recovery from neuromuscular blockade.1 3 57 118 5–9 mcg/kg per minute generally maintains 89–99% neuromuscular blockade in patients receiving balanced anesthesia; however, adequate blockade may occur with infusion rates of 2–15 mcg/kg per minute.1

Initiate continuous IV infusion only after early spontaneous recovery from IV dose is evident.1

Reduce infusion rate by about 33% if steady-state anesthesia has been induced with enflurane or isoflurane.1 (See Specific Drugs under Interactions.)

Consider a smaller reduction in the infusion rate if steady-state anesthesia has been induced with halothane.1 (See Specific Drugs under Interactions.)

Special Populations

Renal Impairment

Dosage adjustments not required.1 2 169 170 171

Burn Patients

Substantially increased doses may be required due to development of resistance.1 143 144 145 146 147 (See Burn Patients under Cautions.)

Cardiopulmonary Bypass Patients with Induced Hypothermia

Infusion rate required to maintain adequate surgical relaxation during hypothermia (i.e., 25–28°C) is approximately 50% of the infusion rate necessary in normothermic patients.1 57 79

Intensive Care Settings

Average infusion rates of 11–13 mcg/kg per minute (range: 4.5–29.5 mcg/kg per minute) have been used in adults; infusion rates may be higher in pediatric patients.1 Dosage requirements may increase or decrease with time.168 (See Intensive Care Settings under Cautions.)

Patients with Myasthenia Gravis

Administer at low initial doses and with careful monitoring in well-controlled patients whose usual therapy is continued up to the time of surgery.114 115 116 130

Patients with Cardiovascular Disease

Initial dose of 0.3–0.4 mg/kg administered slowly or in fractional doses over 1 minute.1 2 132 169 170 171 (See Cardiovascular Effects under Cautions.)

Other Populations

Patients with an increased risk of histamine release (e.g., history of severe anaphylactoid reactions or asthma): Initial dose of 0.3–0.4 mg/kg administered slowly or in fractional doses over 1 minute.1 2 132 169 170 171

Patients in whom potentiation of neuromuscular blockade or difficulties with reversal of blockade may occur (e.g., neuromuscular disease, severe electrolyte disturbances, carcinomatosis): Consider dosage reduction.1 2 However, no clinical experience to date in these patients, and no specific doses are recommended.1 2 (See Neuromuscular Disease and also Electrolyte Disturbances under Cautions.)

Cautions for Tracrium

Contraindications

  • Known hypersensitivity to atracurium besylate or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Respiratory Effects

Potential for severely compromised respiratory function and respiratory paralysis.80 81 82 83 86

Should be used only by individuals experienced in the use of neuromuscular blocking agents and in the maintenance of an adequate airway and respiratory support.1 Facilities and personnel necessary for intubation, administration of oxygen, and assisted or controlled respiration should be immediately available.1

IV cholinesterase inhibitor (e.g., neostigmine, pyridostigmine, edrophonium) should be readily available.1 80 89 (See Reversal of Neuromuscular Blockade under Dosage and Administration.)

Use with caution in patients with pulmonary impairment or respiratory depression.b

Sensitivity Reactions

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylactic or anaphylactoid reactions, reported.1

Use with caution and at lower initial doses in patients with a history of severe anaphylactoid reactions.1 2

General Precautions

Neuromuscular Disease

Possible exaggerated neuromuscular blockade in patients with neuromuscular disease (e.g., myasthenia gravis, Eaton-Lambert syndrome).1 2 114 115 116

Monitor degree of neuromuscular blockade with a peripheral nerve stimulator; consider dosage reduction.1 2 114 115 116

Burn Patients

Resistance to therapy1 143 144 145 147 148 can develop in burn patients, particularly those with burns over 25–30% or more of body surface area.143 144 145 146 147 148 149

Resistance generally becomes apparent ≥1 week after the burn,143 144 145 146 147 148 149 peaks ≥2 weeks after the burn,144 145 146 148 persists for several months or longer,144 146 and decreases gradually with healing.143 144 146 148

Consider possible need for substantially increased doses.1 143 144 145 146 147 (See Distribution: Special Populations, under Pharmacokinetics.)

Histamine Release

Possible substantial histamine release.1 2

Use with caution and at lower initial doses in patients in whom substantial histamine release would be particularly hazardous (e.g., those with clinically important cardiovascular disease) and in patients with any history suggesting a greater risk of histamine release (e.g., history of severe anaphylactoid reactions or asthma).1 2

Safety in patients with asthma not established.1

Cardiovascular Effects

Exhibits minimal effects on heart rate;4 9 12 13 14 31 36 41 67 therefore, will not counteract the bradycardia induced by many anesthetic agents or by vagal stimulation.1 2

Use with caution and at lower initial doses in patients with clinically important cardiovascular disease because of potential for substantial histamine release.1 2

Intensive Care Setting

Possible prolonged paralysis and/or muscle weakness or atrophy.b

Continuous monitoring of neuromuscular transmission recommended during neuromuscular blocking agent therapy in intensive care setting.168 Do not administer additional doses before there is a definite response to nerve stimulation tests.168 If no response is elicited, discontinue administration until a response returns.168

Seizures reported rarely in patients with predisposing factors (e.g., head trauma, cerebral edema, hypoxic encephalopathy, viral encephalitis, uremia) receiving continuous IV infusions for facilitation of mechanical ventilation in intensive care settings.168

Electrolyte Disturbances

Monitor the degree of neuromuscular blockade with a peripheral nerve stimulator and consider dosage reduction in patients with severe electrolyte disturbances (i.e., hypermagnesemia, hypokalemia, hypocalcemia).1 2 86

Malignant Hyperthermia

Malignant hyperthermia is rarely associated with use of neuromuscular blocking agents and/or potent inhalation anesthetics.1 137 139 141 b Be vigilant for its possible development and prepared for its management in any patient undergoing general anesthesia.1 141

Carcinomatosis

Monitor the degree of neuromuscular blockade with a peripheral nerve stimulator and consider dosage reduction.1 2 86

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether atracurium is distributed into milk.1 Caution advised if used in nursing women.1

Pediatric Use

Safety and efficacy not established in children <1 month of age.132

Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity in neonates;1 161 162 163 164 165 166 each mL of atracurium besylate injection in multiple-dose vials contains 9 mg of benzyl alcohol.1

Geriatric Use

Use with caution.b However, no substantial differences in safety, efficacy, or dosage requirements relative to younger adults.1

Hepatic Impairment

Use with caution.b

Renal Impairment

Use with caution.b

Common Adverse Effects

Skin flush.1

Interactions for Tracrium

Specific Drugs

Drug

Interaction

Comments

Anesthetics, general (enflurane, halothane, isoflurane)

Increased potency and prolonged duration of neuromuscular blockade1 10 24 31 35

Reduced atracurium dosage recommended1 (See Dosage under Dosage and Administration)

Anticonvulsants (carbamazepine, phenytoin)

Decreased duration and/or degree of neuromuscular blockadeb

Close monitoring recommended; adjust atracurium dose accordinglyb

Anti-infectives (aminoglycosides, bacitracin, clindamycin, lincomycin, polymyxins, tetracyclines)

Possible increased neuromuscular blockade1 b

Lithium

Possible increased neuromuscular blockade1

Magnesium salts

Possible increased neuromuscular blockade1 b

Use with caution1 b

Neuromuscular blocking agents, nondepolarizing

Possible increased or decreased neuromuscular blockade1 169 170 171

Procainamide

Possible increased neuromuscular blockade1

Quinidine

Possible increased neuromuscular blockade1

Succinylcholine

Variable effects (increased128 129 or decreased117 neuromuscular blockade) reported1

Administer atracurium in reduced dosage and only after patient has recovered from succinylcholine-induced neuromuscular blockade1

Tracrium Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from the GI tract.b

Onset

Time to maximum neuromuscular blockade decreases as the dose increases.1 22 24 39

Following IV administration of 0.4–0.5 mg/kg, maximum neuromuscular blockade generally occurs within 3–5 minutes1 2 (range: 1.7–10 minutes).5 22 26 27 35 40

Duration

Duration of maximum neuromuscular blockade increases as the dose increases.1 22 24 35 39

Duration of neuromuscular blockade induced by 0.4–0.5 mg/kg under balanced anesthesia is about 20–35 minutes.1 2 17 35 86 Recovery generally is 25 and 95% complete approximately 35–45 and 60–70 minutes, respectively, after the injection.1 86 169 170 171

Regardless of the dose, recovery from the maximum effect of neuromuscular blockade is 95% complete in approximately 30 minutes1 (range: 12–75.7 minutes)2 6 22 24 26 31 39 100 under balanced anesthesia and approximately 40 minutes1 (range: 6–104 minutes)5 6 24 27 34 100 under anesthesia with enflurane, isoflurane, or halothane.

Rate of recovery from neuromuscular blockade is more rapid in children than adults.41 88 92

Alkalosis may enhance recovery.3 54

Special Populations

Hepatic dysfunction does not substantially alter duration of and rate of recovery from neuromuscular blockade.19 40 49 103 104 105 106 131

In patients with renal failure, onset may be slightly delayed;40 103 105 however, renal dysfunction does not substantially alter duration of and rate of recovery from neuromuscular blockade.19 40 49 103 104 105 106 131

In patients undergoing cardiopulmonary bypass surgery under induced hypothermia, duration of blockade may be prolonged.57 79 97

Distribution

Extent

Distributed into extracellular fluid;2 85 rapidly reaches site of action at motor end-plate of myoneural junction.b

Crosses the placenta in small amounts.1 2 61 107

Plasma Protein Binding

82%.45 46

Special Populations

In burn patients, possible increased protein binding (possibly to α1-acid glycoprotein) with subsequent decreases in the free fraction of circulating drug.143 144 145 147

Elimination

Metabolism

Rapidly metabolized via Hofmann elimination and nonspecific enzymatic ester hydrolysis; the liver does not appear to play a major role.1 9 31

Elimination Route

Excreted principally in urine and also in feces via biliary elimination.1 2 3 9 22 31 54 108 109 160

Half-life

Biphasic; terminal elimination half-life is approximately 20 minutes.1 2 47 48 49 50 104

Stability

Storage

Parenteral

Injection

2–8°C; do not freeze.1 2

Use within 14 days once removed from refrigeration, regardless of whether injection was subsequently rerefrigerated.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Unstable in the presence of acids and bases.2 May be incompatible with alkaline solutions (e.g., barbiturate solutions).1

Solution CompatibilityHID

Compatible for 24 hours at 5 or 25°C;HID use within 24 hours when diluted with dextrose 5% in water or sodium chloride 0.9% injection.1

Compatible

Dextrose 5% in sodium chloride 0.9%

Incompatible

Ringer’s injection, lactated

Variable

Dextrose 5% in water

Sodium chloride 0.9%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Bretylium tosylate

Cimetidine HCl

Ciprofloxacin

Dobutamine HCl

Dopamine HCl

Esmolol HCl

Gentamicin sulfate

Isoproterenol HCl

Lidocaine HCl

Morphine sulfate

Potassium chloride

Procainamide HCl

Vancomycin HCl

Incompatible

Aminophylline

Cefazolin sodium

Heparin sodium

Quinidine gluconate

Ranitidine HCl

Sodium nitroprusside

Y-Site CompatibilityHID

Compatible

Amiodarone HCl

Cefazolin

Cefuroxime sodium

Cimetidine HCl

Co-trimoxazole

Dobutamine HCl

Dopamine HCl

Epinephrine HCl

Esmolol HCl

Etomidate

Fenoldopam mesylate

Fentanyl citrate

Gentamicin sulfate

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydrocortisone sodium succinate

Isoproterenol HCl

Lorazepam

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nitroglycerin

Ranitidine HCl

Sodium nitroprusside

Vancomycin HCl

Incompatible

Diazepam

Propofol

Thiopental sodium

Actions

  • Produces skeletal muscle relaxation by causing a decreased response to acetylcholine (ACh) at the myoneural (neuromuscular) junction of skeletal muscle.1 b

  • Exhibits high affinity for ACh receptor sites and competitively blocks access of ACh to motor end-plate of myoneural junction; may affect ACh release.b

  • Blocks the effects of both the small quantities of ACh that maintain muscle tone and the large quantities of ACh that produce voluntary skeletal muscle contraction; does not alter the resting electrical potential of the motor end-plate or cause muscular contractions.b

  • Exhibits minimal cardiovascular effects.2 5 6 7 8 9 12 13 14 15 20 22 24 25 26 27 28 88 93

Advice to Patients

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular disease, neuromuscular disease).1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Atracurium Besylate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV use

10 mg/mL*

Atracurium Besylate Injection (preservative-free in single-use vials or with benzyl alcohol 0.9% in multiple-dose vials)

Baxter, Bedford, Hospira, Mayne, Sicor

Tracrium (preservative-free in single-use vials or with benzyl alcohol 0.9% in multiple-dose vials)

Abbott

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Abbott Laboratories. Tracrium (atracurium besylate) injection prescribing information. North Chicago, IL; 2000 Mar.

2. Burroughs Wellcome Co. Tracrium pharmacist product information. Research Triangle Park, NC; 1983 Dec.

3. Collins GE. (Burroughs Wellcome Co, Research Triangle Park, NC): Personal communication; 1984 Mar 22.

4. Lee C, Yang E, Katz RL. Clinical neuromuscular pharmacology of BW 33A. Anesth Analg. 1982; 61:199-200.

5. Goudsouzian NG, Liu LMP, Coté CJ et al. Safety and efficacy of atracurium in adolescents and children anesthetized with halothane. Anesthesiology. 1983; 59:459-62. [IDIS 178106] [PubMed 6688932]

6. Rupp SM, Fahey MR, Miller RD. Neuromuscular and cardiovascular effects of atracurium during nitrous oxide-fentanyl and nitrous oxide-isoflurane anaesthesia. Br J Anaesth. 1983; 55(Suppl 1): 67-70S. [IDIS 172717] [PubMed 6688020]

7. Brandom BW, Woelfel SK, Cook DR et al. Clinical pharmacology of atracurium in infants. Anesthesiology. 1983; 59:A440.

8. Hunt TM, Hughes R, Payne JP. Preliminary studies with atracurium in anaesthetized man. Br J Anaesth. 1980; 52:238-9P.

9. Basta SJ, Ali HH, Savarese JJ et al. Clinical pharmacology of atracurium besylate (BW 33A): a new non-depolarizing muscle relaxant. Anesth Analg. 1982; 61:723-9. [IDIS 157360] [PubMed 6213181]

10. Savarese JJ, Basta SJ, Ali HH et al. Neuromuscular and cardiovascular effects of BW 33A (atracurium) in patients under halothane anesthesia. Anesthesiology. 1982; 57:A262.

11. Basta SJ, Savarese JJ, Ali HH et al. Histamine-releasing potencies of atracurium besylate (BW 33A), metocurine, and d-tubocurarine. Anesthesiology. 1982; 57:A261.

12. Barnes PK, Thomas VJE, Boyd I et al. Comparison of the effects of atracurium and tubocurarine on heart rate and arterial pressure in anaesthetized man. Br J Anaesth. 1983; 55(Suppl 1):91-4S.

13. Basta SJ, Savarese JJ, Ali HH et al. Histamine-releasing potencies of atracurium, dimethyl tubocurarine and tubocurarine. Br J Anaesth. 1983; 55(Suppl 1):105-6S. [IDIS 172726] [PubMed 6338892]

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15. Hughes R, Payne JP. Clinical assessment of atracurium using the single twitch and tetanic responses of the adductor pollicis muscles. Br J Anaesth. 1983; 55(Suppl 1):47-52S.

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17. Foldes FF, Nagashima H, Boros M et al. Muscular relaxation with atracurium, vecuronium and duador under balanced anesthesia. Br J Anaesth. 1983; 55:(Suppl 1):97-103S. [IDIS 172725] [PubMed 6190489]

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22. Hilgenberg JC. Comparison of the pharmacology of vecuronium and atracurium with that of other currently available muscle relaxants. Anesth Analg. 1983; 62:524-31. [IDIS 170170] [PubMed 6132564]

23. Anon. Atracurium. Lancet. 1983; 1:394-5. [PubMed 6130383]

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28. Robertson EN, Booij LHDJ, Fragen RJ et al. Clinical comparison of atracurium and vecuronium (ORG NC 45). Br J Anaesth. 1983; 55:125-9. [IDIS 165994] [PubMed 6131682]

29. Rosewarne FA. Vecuronium and atracurium. Br J Anaesth. 1983; 55:1042. [IDIS 176811] [PubMed 6138052]

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33. Brandom BW, Woelfel SK, Cook DR et al. Relative potency of atracurium in children during halothane, isoflurane, or thiopental-fentanyl anesthesia. Anesthesiology. 1983; 59:A442.

34. Goudsouzian NG, Liu LMP, Coté CJ et al. Clinical pharmacology of atracurium (BW 33A) in adolescents anesthetized with halothane. Anesthesiology. 1982; 57:A414.

35. Sokoll MD, Gergis SD, Mehta M et al. Safety and efficacy of atracurium (BW 33A) in surgical patients receiving balanced or isoflurane anesthesia. Anesthesiology. 1983; 58:450-5. [IDIS 170743] [PubMed 6340561]

36. Nguyen HD, Nagashima H, Kaplan R et al. Relaxation with BW33A under neurolept and enflurane anesthesia. Anesthesiology. 1982; 57:A277.

37. Ramsey FM, White PA, Stullken EH et al. Enflurane potentiation of neuromuscular blockade by atracurium. Anesthesiology. 1982; 57:A255.

38. Cook DR, Rudd GD, Brandom BW. Clinical pharmacology of atracurium (BW33A) in pediatric patients. Anesthesiology. 1982; 57:A415.

39. Hughes R, Hunt TM, Payne JP. Recovery from neuromuscular blockade by atracurium. Br J Anaesth. 1980; 52:634P.

40. Hunter JM, Jones RS, Utting JE. Use of atracurium in patients with no renal function. Br J Anaesth. 1982; 54:1251-8. [IDIS 161973] [PubMed 7171411]

41. Brandom BW, Rudd GD, Cook DR. Clinical pharmacology of atracurium in paediatric patients. Br J Anaesth. 1983; 55(Suppl 1):117-21S.

42. Hunter JM, Jones RS, Utting JE. Use of atracurium during general surgery monitored by the train-of-four stimuli. Br J Anaesth. 1982; 54:1243-50. [IDIS 161972] [PubMed 7171410]

43. Ali HH, Savarese JJ, Basta SJ et al. Evaluation of cumulative properties of three new non-depolarizing neuromuscular blocking drugs BW A444U, atracurium and vecuronium. Br J Anaesth. 1983; 55(Suppl 1):107-11S.

44. Hughes R, Payne JP. Assessment of atracurium blockade in man by single twitch and tetanic stimulation. Br J Anaesth. 1981; 53:1101-2.

45. Foldes FF, Deery A, Benad G et al. The binding of neuromuscular blocking agents to plasma proteins. Anesthesiology. 1982; 57:A274.

46. Foldes FF, Deery A. Protein binding of atracurium and other short-acting neuromuscular blocking agents and their interaction with human cholinesterases. Br J Anaesth. 1983; 55(Suppl 1):31-4S.

47. Weatherley BC, Williams SG, Neill EAM. Pharmacokinetics, pharmacodynamics and dose-response relationships of atracurium administered I.V. Br J Anaesth. 1983; 55(Suppl 1):39-45S.

48. Ward S, Wright D, Corall I et al. Combined pharmacokinetic and pharmacodynamic studies with atracurium besylate (in normal patients and patients with hepatic and renal failure). Can Anaesth Soc J. 1983; 30:S81-2.

49. Ward S, Neill EAM. Pharmacokinetics of atracurium in acute hepatic failure (with acute renal failure). Br J Anaesth. 1983; 55:1169-72. [IDIS 179715] [PubMed 6689126]

50. Ward S, Neill EAM, Weatherley BC et al. Pharmacokinetics of atracurium besylate in healthy patients (after a single I.V. bolus dose). Br J Anaesth. 1983; 55:113-8. [IDIS 165992] [PubMed 6687550]

51. Utting JE, Hunter JM, Jones RS. Atracurium in patients with no renal function. Anesthesiology. 1982; 57:A252.

52. Hughes R, Azawi SA, Hunt TM et al. Further studies with atracurium. Br J Anaesth. 1980; 52:956-7P.

53. Merrett RA, Thompson CW, Webb FW. In vitro degradation of atracurium in human plasma. Br J Anaesth. 1983; 55:61-6. [PubMed 6687375]

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