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CISATRACURIUM

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Cisatracurium besylate is an intermediate onset/intermediate duration non-depolarizing neuromuscular blocking agent. Cisatracurium besylate is one of ten isomers of atracurium besylate and constitutes 15% of that mixture. Cisatracurium competes with acetylcholine for cholinergic postjunctional receptor sites but lacks the transmitter action of acetylcholine.

Specific Substances

    1) 51W89
    2) Cisatracurium besylate
    3) Cisatracurium besilate
    4) CAS 96956-42-8

Available Forms Sources

    A) FORMS
    1) Cisatracurium is available as 2 mg/mL injection solution and 2 mg/mL and 10 mg/mL intravenous solution (Prod Info CISATRACURIUM intravenous injection solution, 2015).
    B) USES
    1) Cisatracurium besylate, an intermediate-onset/duration neuromuscular blocking agent, is used as an adjunct to general anesthesia, to facilitate tracheal intubation, and to provide skeletal muscle relaxation during surgery or mechanical ventilation in the ICU (Prod Info CISATRACURIUM intravenous injection solution, 2015)

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Cisatracurium besylate, an intermediate-onset/duration neuromuscular blocking agent, is used as an adjunct to general anesthesia, to facilitate tracheal intubation, and to provide skeletal muscle relaxation during surgery or mechanical ventilation in the ICU.
    B) PHARMACOLOGY: Cisatracurium besylate is a nondepolarizing neuromuscular blocking agent. Nondepolarizing neuromuscular blocking agents inhibit neuromuscular transmission by competing with acetylcholine for the cholinergic receptors at the motor end plate, thereby antagonizing the action of acetylcholine. This type of competitive neuromuscular blockade is usually antagonized by anticholinesterase agents.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) The following adverse effects have rarely been reported; Hypotension (0.2%), bradycardia (0.4%), bronchospasm (0.2%), muscle weakness, myopathy, and hypersensitivity reactions, including anaphylaxis.
    E) WITH POISONING/EXPOSURE
    1) Overdose with cisatracurium may result in neuromuscular block beyond the time needed for surgery and anesthesia. No unanticipated events have been reported with large doses.
    0.2.20) REPRODUCTIVE
    A) Cisatracurium is classified as FDA pregnancy category B. Studies on animals have found no teratogenic effects.

Laboratory Monitoring

    A) No specific laboratory tests are necessary unless otherwise clinically indicated.
    B) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    C) Monitor vital signs and mental status.
    D) Obtain an ECG, and institute continuous cardiac monitoring.
    E) Monitor pulse oximetry and/or arterial blood gases.

Treatment Overview

    0.4.6) PARENTERAL EXPOSURE
    A) MANAGEMENT OF TOXICITY
    1) Oxygenation, airway protection and ventilation support as indicated. Once airway is established and ventilation is provided, sedate patients with benzodiazepines and opioids as long as neuromuscular blockade is in effect. Monitor vital signs, especially respiration. Obtain an ECG, and institute continuous cardiac monitoring. Reverse neuromuscular blockage effect: Administer IV neostigmine (see antidote below); alternative agents include physostigmine and edrophonium. Administration of atropine sulfate with or before neostigmine has been suggested to counteract the muscarinic side effects of neostigmine. Manage mild hypotension with IV fluids. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids. In most patients, sinus bradycardia is neither significant nor symptomatic, requiring no intervention. However, extreme bradycardia may result in decreased cardiac output and hypotension; IV atropine is first line treatment. If unresponsive, use beta adrenergic agonists (eg, isoproterenol) or temporary cardiac pacemaker. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required.
    B) DECONTAMINATION
    1) Gastrointestinal decontamination is not recommended; administered via the parenteral route.
    C) AIRWAY MANAGEMENT
    1) Patients who cannot protect their own airway or have signs and symptoms of respiratory failure may need intubation for respiratory support.
    D) ELECTRICAL NERVE STIMULATION PROCEDURE
    1) The use of a peripheral nerve stimulator to evaluate recovery and antagonism of neuromuscular block is recommended.
    E) ANTIDOTE
    1) NEOSTIGMINE: ADULT: 0.5 to 2 mg slow IV injection, along with 0.6 to 1.2 mg of atropine sulfate IV in a separate syringe. Repeat as needed; rarely should total dose of neostigmine exceed 5 mg. PEDIATRIC: 0.02 to 0.075 mg/kg IV injection, in addition to atropine 0.01 to 0.02 mg/kg. In the presence of bradycardia, the pulse rate should be increased to about 80 beats/min with atropine before administering neostigmine. Administration of atropine sulfate with or before neostigmine has been suggested to counteract muscarinic side effects. Reversal time following intense neuromuscular blockade induced by atracurium may be prolonged. Neostigmine may not shorten the time to total recovery from an intense level of blockade. Other agents to consider include edrophonium or physostigmine in conjunction with atropine.
    F) ENHANCED ELIMINATION
    1) The effects of hemofiltration, hemodialysis, hemoperfusion on plasma levels of cisatracurium are unknown. Renal elimination is a major route of elimination for laudanosine, a metabolite of cisatracurium thought to be responsible for anaphylactoid responses. Dialysis may be useful in patients with renal insufficiency in order to minimize the potential for anaphylactoid reactions.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: There is no data to support home management, and these agents are only used in the hospital setting.
    2) OBSERVATION CRITERIA: Following inadvertent intravenous administrations, symptomatic patients should be monitored until they are clearly improving and clinically stable.
    3) ADMISSION CRITERIA: Patients with systemic toxicities or patients with severe symptoms should be admitted to intensive care unit for treatment and closed monitoring.
    4) CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    H) PITFALLS
    1) Failure to detect respiratory failure and compromised airway.
    I) PHARMACOKINETICS
    1) Protein binding: The protein binding of cisatracurium has not been fully evaluated due to its rapid degradation at physiologic pH. Vd: 145 mL/kg. Metabolism: The liver and kidney play a minor role in the elimination of cisatracurium; however these 2 organ systems play a major role in the elimination of metabolites. Excretion: 95% of a radiolabeled dose was recovered in the urine (less than 10% of the dose was excreted as unchanged parent drug). Elimination half-life: Approximately 22 to 31 minutes.
    J) DIFFERENTIAL DIAGNOSIS
    1) Botulism, neurotoxic snake bite, succinylcholine toxicity, organophosphorus or carbamate toxicity, myasthenia gravis, Guillain-Barre syndrome, tick paralysis.

Range Of Toxicity

    A) TOXICITY: Doses up to 8 times the ED95 (dose required to produce 95% suppression of the twitch response to peripheral nerve stimulation) or 0.4 mg/kg have been safely administered to healthy adult patients.
    B) THERAPEUTIC DOSE: ADULTS: Initial dose: 0.15 (3 times the ED95) mg/kg or 0.2 (4 times the ED95) mg/kg cisatracurium as components of a propofol/nitrous oxide/oxygen induction-intubation technique; may produce good to excellent conditions for tracheal intubation in 2 and 1.5 minutes, respectively. Maintenance dose: 0.03 mg/kg, as determined by clinical criteria, 40 to 50 minutes following initial 0.15 mg/kg dose or 50 to 60 minutes following 0.20 mg/kg dose. PEDIATRIC: CHILDREN 2 TO 12 YEARS OLD: Initial dose, 0.1 to 0.15 mg/kg administered over 5 to 10 seconds during either halothane or opioid anesthesia. INFANTS 1 MONTH TO 23 MONTHS: Initial dose, 0.15 mg/kg administered over 5 to 10 seconds during either halothane or opioid anesthesia. INFANTS LESS THAN 1 MONTH OLD: Safety and efficacy in infants less than 1 month old have not been established.

Clinical Effects

Summary Of Exposure

    A) USES: Cisatracurium besylate, an intermediate-onset/duration neuromuscular blocking agent, is used as an adjunct to general anesthesia, to facilitate tracheal intubation, and to provide skeletal muscle relaxation during surgery or mechanical ventilation in the ICU.
    B) PHARMACOLOGY: Cisatracurium besylate is a nondepolarizing neuromuscular blocking agent. Nondepolarizing neuromuscular blocking agents inhibit neuromuscular transmission by competing with acetylcholine for the cholinergic receptors at the motor end plate, thereby antagonizing the action of acetylcholine. This type of competitive neuromuscular blockade is usually antagonized by anticholinesterase agents.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) The following adverse effects have rarely been reported; Hypotension (0.2%), bradycardia (0.4%), bronchospasm (0.2%), muscle weakness, myopathy, and hypersensitivity reactions, including anaphylaxis.
    E) WITH POISONING/EXPOSURE
    1) Overdose with cisatracurium may result in neuromuscular block beyond the time needed for surgery and anesthesia. No unanticipated events have been reported with large doses.

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) A very slight incidence (0.2%) of hypotension has been reported following the administration of therapeutic doses ranging from 2 to 8 times the ED95 (0.1 to 0.4 milligram/kilogram) when infused over 5 to 10 seconds (Prod Info CISATRACURIUM intravenous injection solution, 2015).
    B) BRADYCARDIA
    1) WITH THERAPEUTIC USE
    a) A very slight incidence (0.4%) of bradycardia has been reported following the administration of therapeutic doses ranging from 2 to 8 times the ED95 (0.1 to 0.4 milligram/kilogram) when infused over 5 to 10 seconds (Prod Info CISATRACURIUM intravenous injection solution, 2015).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) BRONCHOSPASM
    1) WITH THERAPEUTIC USE
    a) During clinical trials of 945 surgery patients in the United States and Europe, bronchospasm was experienced in 0.2% of patients receiving cisatracurium in conjunction with other drugs (Prod Info CISATRACURIUM intravenous injection solution, 2015).
    b) SURGICAL PATIENTS: Very slight incidence (0.2%) of bronchospasm has been reported following the administration of therapeutic doses ranging from 2 to 8 times the ED95 (0.1 to 0.4 milligram/kilogram) when infused over 5 to 10 seconds (Prod Info CISATRACURIUM intravenous injection solution, 2015).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) PROLONGED NEUROMUSCULAR BLOCK
    1) WITH THERAPEUTIC USE
    a) During post-marketing use of cisatracurium in conjunction with one or more anesthetic agents, prolonged neuromuscular block has been reported (Prod Info CISATRACURIUM intravenous injection solution, 2015).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) FLUSHING
    1) WITH THERAPEUTIC USE
    a) A very slight incidence (0.2%) of flushing has been reported following the administration of therapeutic doses ranging from 2 to 8 times the ED95 (0.1 to 0.4 milligram/kilogram) when infused over 5 to 10 seconds (Prod Info Nimbex(R) injection, cisatracurium besylate, 1999).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) DRUG-INDUCED MYOPATHY
    1) WITH THERAPEUTIC USE
    a) During post-marketing use of cisatracurium in conjunction with one or more anesthetic agents, myopathy has been reported (Prod Info CISATRACURIUM intravenous injection solution, 2015).
    b) CASE REPORT: A 45-year-old woman required inverse ratio mechanical ventilation and was paralyzed with cisatracurium. Infusion rates ranged from 6.3 to 10.5 micrograms/kilogram/minute with normal peripheral nerve assessment. Cisatracurium was discontinued after 11 days, and the patient had severe proximal and distal muscle weakness of both upper and lower extremities. She was unable to move until 11 days after the infusion was discontinued, at which point she could move her fingertips. No sensory deficits were observed. By ICU day 33, the patient was weaned from mechanical ventilation and required extensive rehabilitative (occupational and physical) therapy for several months (Davis et al, 1998).
    B) MUSCLE WEAKNESS
    1) WITH THERAPEUTIC USE
    a) During post-marketing use of cisatracurium in conjunction with one or more anesthetic agents, muscle weakness has been reported (Prod Info CISATRACURIUM intravenous injection solution, 2015).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) HYPERSENSITIVITY REACTION
    1) WITH THERAPEUTIC USE
    a) During post-marketing use of cisatracurium in conjunction with one or more anesthetic agents, hypersensitivity reactions have been reported (Prod Info CISATRACURIUM intravenous injection solution, 2015).
    B) ANAPHYLAXIS
    1) WITH THERAPEUTIC USE
    a) During post-marketing use of cisatracurium in conjunction with one or more anesthetic agents, anaphylaxis and anaphylactoid responses have been reported, which in rare instances were severe (Prod Info CISATRACURIUM intravenous injection solution, 2015).

Reproductive

    3.20.1) SUMMARY
    A) Cisatracurium is classified as FDA pregnancy category B. Studies on animals have found no teratogenic effects.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) There were no reports of maternal or fetal toxicity or teratogenic effects during animal studies with cisatracurium doses up to approximately 20 times the recommended human dose (Prod Info NIMBEX(R) intravenous injection, 2013).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) The manufacturer has classified cisatracurium as FDA pregnancy category B (Prod Info NIMBEX(R) intravenous injection, 2013).
    2) Exercise caution when administering to a pregnant woman and use only if clearly needed (Prod Info NIMBEX(R) intravenous injection, 2013).
    B) LABOR OR DELIVERY
    1) The neuromuscular blocking action of agents may be enhanced by administration of magnesium salts for management of toxemia of pregnancy (Prod Info NIMBEX(R) intravenous injection, 2013).
    C) ANIMAL STUDIES
    1) Administration of cisatracurium during cesarean section in animals resulted in small levels of cisatracurium in umbilical vessel blood of the offspring. No deleterious effects were noted in the offspring (Prod Info NIMBEX(R) intravenous injection, 2013).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) RISK SUMMARY
    1) It is unknown whether cisatracurium is excreted in human milk. Due to the potential for adverse reactions in the nursing infant, exercise caution when administering to lactating women (Prod Info NIMBEX(R) intravenous injection, 2013).

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) Carcinogenesis studies have not been performed.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific laboratory tests are necessary unless otherwise clinically indicated.
    B) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    C) Monitor vital signs and mental status.
    D) Obtain an ECG, and institute continuous cardiac monitoring.
    E) Monitor pulse oximetry and/or arterial blood gases.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.2) DISPOSITION/PARENTERAL EXPOSURE
    6.3.2.1) ADMISSION CRITERIA/PARENTERAL
    A) Patients with systemic toxicities or patients with severe symptoms should be admitted to intensive care unit for treatment and closed monitoring.
    6.3.2.2) HOME CRITERIA/PARENTERAL
    A) There is no data to support home management, and these agents are only used in the hospital setting.
    6.3.2.3) CONSULT CRITERIA/PARENTERAL
    A) Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.2.5) OBSERVATION CRITERIA/PARENTERAL
    A) Following inadvertent intravenous administrations, symptomatic patients should be monitored until they are clearly improving and clinically stable.

Monitoring

    A) No specific laboratory tests are necessary unless otherwise clinically indicated.
    B) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    C) Monitor vital signs and mental status.
    D) Obtain an ECG, and institute continuous cardiac monitoring.
    E) Monitor pulse oximetry and/or arterial blood gases.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Gastrointestinal decontamination is not recommended; administered via the parenteral route.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Refer to parenteral exposure treatment for further information.

Enhanced Elimination

    A) DIALYSIS PROCEDURE
    1) The effects of hemofiltration, hemodialysis, hemoperfusion on plasma levels of cisatracurium are unknown (Prod Info CISATRACURIUM intravenous injection solution, 2015).
    2) Renal elimination is a major route of elimination for laudanosine, a metabolite of cisatracurium thought to be responsible for anaphylactoid responses. Dialysis may be useful in patients with renal insufficiency in order to minimize the potential for anaphylactoid reactions (Prod Info CISATRACURIUM intravenous injection solution, 2015).

Range Of Toxicity

Summary

    A) TOXICITY: Doses up to 8 times the ED95 (dose required to produce 95% suppression of the twitch response to peripheral nerve stimulation) or 0.4 mg/kg have been safely administered to healthy adult patients.
    B) THERAPEUTIC DOSE: ADULTS: Initial dose: 0.15 (3 times the ED95) mg/kg or 0.2 (4 times the ED95) mg/kg cisatracurium as components of a propofol/nitrous oxide/oxygen induction-intubation technique; may produce good to excellent conditions for tracheal intubation in 2 and 1.5 minutes, respectively. Maintenance dose: 0.03 mg/kg, as determined by clinical criteria, 40 to 50 minutes following initial 0.15 mg/kg dose or 50 to 60 minutes following 0.20 mg/kg dose. PEDIATRIC: CHILDREN 2 TO 12 YEARS OLD: Initial dose, 0.1 to 0.15 mg/kg administered over 5 to 10 seconds during either halothane or opioid anesthesia. INFANTS 1 MONTH TO 23 MONTHS: Initial dose, 0.15 mg/kg administered over 5 to 10 seconds during either halothane or opioid anesthesia. INFANTS LESS THAN 1 MONTH OLD: Safety and efficacy in infants less than 1 month old have not been established.

Therapeutic Dose

    7.2.1) ADULT
    A) ROUTE OF ADMINISTRATION
    1) INITIAL DOSES
    a) 0.15 (3 times the ED95) mg/kg or 0.20 (4 times the ED95) mg/kg cisatracurium as components of a propofol/nitrous oxide/oxygen induction-intubation technique; may produce good to excellent conditions for tracheal intubation in 2 and 1.5 minutes, respectively. Similar results have been found with thiopental/nitrous oxide/oxygen induction-intubation technique (Prod Info cisatracurium besylate intravenous injection, 2012).
    2) MAINTENANCE DOSE
    a) 0.03 mg/kg, as determined by clinical criteria, 40 to 50 minutes following initial 0.15 mg/kg dose or 50 to 60 minutes following 0.20 mg/kg dose (Prod Info cisatracurium besylate intravenous injection, 2012)
    3) USE IN OPERATING ROOM
    a) An initial infusion rate of 3 mcg/kg/minute, thereafter, a rate of 1 to 2 mcg/kg/minute to maintain continuous neuromuscular block in the range of 89% to 99% in most adult patients (Prod Info cisatracurium besylate intravenous injection, 2012)
    b) Reduction of the infusion rate by 30% to 40% may be needed when cisatracurium is administered during stable isoflurane or enflurane anesthesia (Prod Info cisatracurium besylate intravenous injection, 2012).
    4) USE IN INTENSIVE CARE
    a) An infusion rate of approximately 3 mcg/kg/minute, with a range of 0.5 to 10.2 mcg/kg/minute (Prod Info cisatracurium besylate intravenous injection, 2012)
    7.2.2) PEDIATRIC
    A) INFANTS LESS THAN 1 MONTH OLD: Safety and efficacy in infants less than 1 month old have not been established (Prod Info cisatracurium besylate intravenous injection, 2012).
    B) INFANTS 1 MONTH TO 23 MONTHS: Initial dose, 0.15 mg/kg administered over 5 to 10 seconds during either halothane or opioid anesthesia(Prod Info cisatracurium besylate intravenous injection, 2012)
    C) CHILDREN 2 TO 12 YEARS OLD: Initial dose, 0.10 to 0.15 mg/kg administered over 5 to 10 seconds during either halothane or opioid anesthesia (Prod Info cisatracurium besylate intravenous injection, 2012)
    D) USE IN OPERATING ROOM
    1) An initial infusion rate of 3 mcg/kg/minute; thereafter, a rate of 1 to 2 mcg/kg/minute to maintain continuous neuromuscular block in the range of 89% to 99% in most pediatric patients (Prod Info cisatracurium besylate intravenous injection, 2012)
    2) Reduction of the infusion rate by 30% to 40% may be needed when cisatracurium is administered during stable isoflurane or enflurane anesthesia (Prod Info cisatracurium besylate intravenous injection, 2012).
    E) USE IN INTENSIVE CARE
    1) An infusion rate of approximately 3 mcg/kg/minute, with a range of 0.5 to 10.2 mcg/kg/minute (Prod Info cisatracurium besylate intravenous injection, 2012)

Maximum Tolerated Exposure

    A) Doses up to 8 times the ED95 (dose required to produce 95% suppression of the twitch response to peripheral nerve stimulation) or 0.4 mg/kg have been safely administered to healthy adult patients (Prod Info CISATRACURIUM intravenous injection solution, 2015).

References

General Bibliography

    1) AMA Council on Drugs: AMA Drug Evaluations, 5th ed, American Medical Association, Chicago, IL, 1983.
    2) Bevan JC, Collins L, Fowler C, et al: Early and late reversal of rocuronium and vecuronium with neostigmine in adults and children. Anesth Analg 1999; 89(2):333-339.
    3) Bevan JC, Purday JP, Reimer EJ, et al: Reversal of doxacurium and pancuronium neuromuscular blockade with neostigmine in children. Can J Anaesth 1994; 41(11):1074-1080.
    4) Boyd AH, Eastwood NB, & Parker CJR: Comparison of the pharmacodynamics and pharmacokinetics of an infusion of cis-atracurium (51 W89) or atracurium in critically ill patients undergoing mechanical ventilation in an intensive therapy unit. Br J Anaesth 1996; 76:382-388.
    5) Boyd AH, Eastwood NB, & Parker CJR: Pharmacodynamics of the 1R cis-1'R cis isomer of atracurium (51W89) in health and chronic renal failure. Br J Anaesthesia 1995; 74:400-404.
    6) Davis NA, Rodgers JE, & Gonzalez ER: Prolonged weakness after cisatracurium infusion: A case report. Crit Care Med 1998; 26:1290-1292.
    7) De MP & Paul AK: Clinical experiences with vecuronium in children. J Indian Med Assoc 1991; 89(5):125-127.
    8) Engbaek J, Ostergaard D, & Skovgaard LT: Reversal of intense neuromuscular blockade following infusion of atracurium. Anesthesiology 1990; 72:803-806.
    9) Esener Z: A clinical study on vecuronium in children: a comparison with fazadinium and pancuronium. Turk J Pediatr 1988; 30(3):163-172.
    10) Fisher DM, Cronnelly R, Miller RD, et al: The neuromuscular pharmacology of neostigmine in infants and children. Anesthesiology 1983; 59(3):220-225.
    11) Gwinnutt CL, Walker RW, & Meakin G: Antagonism of intense atracurium-induced neuromuscular block in children. Br J Anaesth 1991; 67(1):13-16.
    12) Hull CJ: Pharmacokinetics and pharmacodynamics of the benzylisoquinolinium muscle relaxants. Acta Anaesthesiol Scand 1995; 39(suppl):13-17.
    13) Hunter JM, Eastwood NB, & Boyd AH: Pharmacokinetics of 51W89: preliminary data. Acta Anaesthesiol Scand 1995; 39(suppl):94.
    14) Kisor DF, Schmith VD, & Wargin WA: Importance of the organ-independent elimination of cisatracurium. Anesth Analg 1996; 83:1065-1071.
    15) Kleinman ME, Chameides L, Schexnayder SM, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 14: pediatric advanced life support. Circulation 2010; 122(18 Suppl.3):S876-S908.
    16) Lieberman P, Nicklas R, Randolph C, et al: Anaphylaxis-a practice parameter update 2015. Ann Allergy Asthma Immunol 2015; 115(5):341-384.
    17) Lieberman P, Nicklas RA, Oppenheimer J, et al: The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol 2010; 126(3):477-480.
    18) Lien CA, Belmont MR, & Abalos A: The cardiovascular effects and histamine-releasing properties of 51W89 in patients receiving nitrous oxide/opioid/barbiturate anesthesia. Anesthesiology 1995; 82:1131-1138.
    19) Lysakowski C, Fuchs-Buder T, & Tassonyi E: Mivacurium or vecuronium for paediatric ENT surgery. Clinical experience and cost analysis. Anaesthesist 2000; 49(5):387-391.
    20) Meretoja OA : Neuromuscular blocking agents in paediatric patients: influence of age on the response. Anaesth Intensive Care 1990; 18(4):440-448.
    21) National Heart,Lung,and Blood Institute: Expert panel report 3: guidelines for the diagnosis and management of asthma. National Heart,Lung,and Blood Institute. Bethesda, MD. 2007. Available from URL: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
    22) Neumar RW , Otto CW , Link MS , et al: Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122(18 Suppl 3):S729-S767.
    23) Nowak RM & Macias CG : Anaphylaxis on the other front line: perspectives from the emergency department. Am J Med 2014; 127(1 Suppl):S34-S44.
    24) Peberdy MA , Callaway CW , Neumar RW , et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science. Part 9: post–cardiac arrest care. Circulation 2010; 122(18 Suppl 3):S768-S786.
    25) Product Information: CISATRACURIUM intravenous injection solution, cisatracurium besylate intravenous injection solution. Fesenius Kabi USA (per DailyMed), Lake Zurich, IL, 2015.
    26) Product Information: ENLON(R) intravenous injection, intramuscular injection, edrophonium chloride intravenous injection, intramuscular injection. Bioniche Pharma USA LLC (per manufacturer), Lake Forest, IL, 2009.
    27) Product Information: Fungizone(R), amphotericin B injection. Apothecon, Princeton, NJ, 1998.
    28) Product Information: Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, isoproterenol HCl intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection. Hospira, Inc. (per FDA), Lake Forest, IL, 2013.
    29) Product Information: NIMBEX(R) intravenous injection, cisatracurium besylate intravenous injection. AbbVie Inc. (per Manufacturer), North Chicago, IL, 2013.
    30) Product Information: Nimbex(R) injection, cisatracurium besylate. Glaxo Wellcome Inc, Research Triangle Park, NC, 1999.
    31) Product Information: cisatracurium besylate intravenous injection, cisatracurium besylate intravenous injection. Sandoz Inc. (per DailyMed), Princeton, NJ, 2012.
    32) Product Information: diphenhydramine HCl intravenous injection solution, intramuscular injection solution, diphenhydramine HCl intravenous injection solution, intramuscular injection solution. Hospira, Inc. (per DailyMed), Lake Forest, IL, 2013.
    33) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    34) Product Information: neostigmine methylsulfate IV, IM, subcutaneous injection solution, neostigmine methylsulfate IV, IM, subcutaneous injection solution. American Regent, Inc (Per DailyMed), Shirley, NY, 2009.
    35) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
    36) Ross AK, Dear GL, Dear RB, et al: Onset and recovery of neuromuscular blockade after two doses of rocuronium in children. J Clin Anesth 1998; 10(8):631-635.
    37) Salmenpera M & Nilsson E: Comparison of physostigmine and neostigmine for antagonism of neuromuscular block. Acta Anesth Scand 1981; 25:387-390.
    38) Vanden Hoek,TL; Morrison LJ; Shuster M; et al: Part 12: Cardiac Arrest in Special Situations 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. American Heart Association. Dallas, TX. 2010. Available from URL: http://circ.ahajournals.org/cgi/reprint/122/18_suppl_3/S829. As accessed 2010-10-21.
    39) Welch RM, Brown A, & Ravitch J: The in vitro degradation of cisatracurium, the R cis-R'-isomer of atracurium, in human and rat plasma. Clin Pharmacol Ther 1995; 58:132-142.
    40) de Caen AR, Berg MD, Chameides L, et al: Part 12: Pediatric Advanced Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132(18 Suppl 2):S526-S542.