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HIGH ALERT NEUROMUSCULAR BLOCKING AGENTS (nondepolarizing)
atracurium (a-tra-kyoor-ee-um)
Tracrium
cisatracurium (sis-a-tra-kyoor-ee-um)
Nimbex
doxacurium (dox-a-kyoor-ee-um)
Nuromax
gallamine (gal-a-meen)
Flaxedil
metocurine (me-toe-kyoor-een)
Metubine
mivacurium (miv-a-kyoor-ee-um)
Mivacron
pancuronium (pan-kyoor-oh-nee-um)
Pavulon
pipecuronium (pip-e-kyoor-oh-nee-um)
Arduan
rocuronium (roe-kyoor-own-ee-um)
Zemuron
tubocurarine (too-boh-kyoor-ar-een)
Tubarine
vecuronium (ve-kyoor-oh-nee-um)
Norcuron
Classification
Therapeutic: neuromuscular blocking agents—nondepolarizing
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Induction of skeletal muscle paralysis and facilitation of intubation after induction of anesthesia in surgical procedures. Facilitation of compliance during mechanical ventilation. Metocurine, tubocurarine: Adjunct to electroconvulsive therapy. Tubocurarine: Diagnostic agent for myasthenia gravis.
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Prevent neuromuscular transmission by blocking the effect of acetylcholine at the myoneural junction. Have no analgesic or anxiolytic properties. Therapeutic Effects: Skeletal muscle paralysis.
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Adverse Reactions/Side Effects
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Resp: bronchospasm. CV: tubocurarine: arrhythmias; atracurium, metocurine, tubocurarine: hypotension (↑ with tubocurarine); pancuronium, gallamine: hypertension (↑ with gallamine); atracurium, pancuronium, gallamine: tachycardia (↑ with gallamine). GI: pancuronium: excessive salivation. Derm: rash; atracurium: skin flushing. Misc: ALLERGIC REACTIONS, INCLUDING ANAPHYLAXIS.
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PHYSICAL THERAPY IMPLICATIONS
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Examination and Evaluation
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Monitor signs of allergic reactions and anaphylaxis, including pulmonary symptoms (tightness in the throat and chest, wheezing, cough, dyspnea) or skin reactions (rash, pruritus, urticaria). Notify physician or nursing staff immediately if these reactions occur.
Be alert for residual skeletal muscle weakness that persists after the patient recovers from surgery. Report any strength deficits that might affect gait, balance, and other functional activities.
Assess blood pressure (BP) and compare to normal values (See Appendix F). Report changes in BP, either a problematic decrease in BP (hypotension) or a sustained increase in BP (hypertension).
Assess symptoms of bronchospasm (wheezing, coughing, tightness in chest) or decreased respiratory muscle function. Perform pulmonary function tests to quantify suspected changes in ventilation and respiration (See Appendix I).
Assess heart rate, ECG, and heart sounds, especially during exercise (See Appendices G, H). Report any rhythm disturbances or symptoms of increased arrhythmias, including palpitations, chest discomfort, shortness of breath, fainting, and fatigue/weakness.
If used during mechanical ventilation, observe whether the chest wall is relaxed and compliant with ventilation. Notify physician or nursing staff if the patient is agitated or appears to be resisting mechanical ventilation.
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Patient/Client-Related Instruction
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Absorption: Following IV administration, absorption is essentially complete. Tubocurarine—Although well absorbed following IM administration, effect is delayed as compared with IV administration.
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Distribution: Atracurium, gallamine—Distribute into extracellular space; cross the placenta. Metocurine—Extensively distributed; crosses the placenta. Mivacurium—Tissue distribution is limited. Pancuronium—Rapidly distributes into extracellular fluid; small amounts cross the placenta. Tubocurarine—Extensively distributed and subsequently redistributed to various tissue compartments; saturation of compartments occurs, explaining prolonged duration of action following repeated doses. Vecuronium—Rapidly distributed in extracellular fluid; minimal penetration of the CNS.
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Metabolism and Excretion: Atracurium, mivacurium—Metabolized in plasma. Cisatracurium—Undergoes pH-dependent breakdown, which is responsible for 80% of metabolism; remainder eliminated by liver and kidneys. Doxacurium—Excreted primarily unchanged in urine and bile. Gallamine—Excreted almost entirely unchanged by the kidneys. Metocurine—50% excreted unchanged in urine. Pancuronium—Excreted mostly unchanged by the kidneys; small amounts are eliminated in bile. Pipecuronium—>75% excreted by the kidneys, mostly as unmetabolized drug. Rocuronium—Mostly metabolized by the liver. Tubocurarine—30–75% excreted unchanged by the kidneys; 11% excreted in bile; small amounts are metabolized by the liver. Vecuronium—Some metabolism by the liver (20%), with conversion to at least 1 active metabolite; 35% excreted unchanged by the kidneys.
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Half-life: Atracurium—Infants: 20 min; Children: 17 min; Adults: 16 min; cisatracurium—22–31 min; doxacurium—1.5 hr (increased to 3.7 hr in renal dysfunction and 1.9 hr in liver dysfunction); gallamine—2.5 hr; metocurine—3.6 hr; mivacurium—Trans-trans isomer: 2.3 min; cis-trans isomer 2.1 min; pancuronium—2 hr; pipecuronium—1.7 hr (prolonged in renal impairment); rocuronium—Infants 3–12 mo: 0.8–1.8 hr; Children 1–3 yr: 0.4–1.8 hr; Children 3–8 yr: 0.5–1.1 hr; Adults: 1.4–2.4 hr (increased to 4.3 hr in hepatic impairment and 2.4 hr in renal impairment); tubocurarine—2 hr; vecuronium—Infants: 65 min; Children: 41 min; Adults: 65–75 min (↓ near term in pregnant patients; ↑ in patients with hepatic impairment).
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Contraindications/Precautions
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Contraindicated in: Hypersensitivity; Hypersensitivity to bromides (pancuronium, vecuronium only); Hypersensitivity to iodides/iodine (gallamine, metocurine only); Products containing benzyl alcohol should be avoided in neonates.
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Use Cautiously in: Patients with underlying cardiovascular disease (↑ risk of arrhythmias; less with atracurium or vecuronium); Dehydration or electrolyte abnormalities (should be corrected); Situations in which histamine release would be problematic (worse with atracurium, mivacurium, and doxacurium; less with cisatracurium and vecuronium); Fractures or muscle spasm; Geriatric patients or patients with impaired renal function (slower onset to complete paralysis with cisatracurium; ↓ elimination of gallamine, metocurine, pancuronium, tubocurarine); Hyperthermia (↑ duration/intensity of paralysis); Patients with significant hepatic impairment (↓ metabolism of vecuronium, altered response to others); Shock (prolonged paralysis from gallamine, metocurine, tubocurarine); Extensive burns (may be more resistant to effects of cisatracurium); Low plasma pseudocholinesterase levels (may be seen in association with anemia, dehydration, cholinesterase inhibitors/insecticides, severe liver disease, pregnancy, or hereditary predisposition); Obese patients; Pregnancy, lactation, or children (safety not established for some agents; most agents have been used safely in pregnant women undergoing cesarean section; selected agents have been used safely in children).
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Exercise Extreme Caution in: Patients with neuromuscular diseases such as myasthenia gravis (small test dose may be used to assess response).
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Drug-Drug: Intensity and duration of paralysis may be prolonged by pretreatment with succinylcholine, general anesthesia (inhalation), aminoglycosides, vancomycin, tetracyclines, polymyxin B, colistin, clindamycin, lidocaine, and other local anesthetics, lithium, quinidine, procainamide, beta-adrenergic blocking agents, potassium-losing diuretics, or magnesium. Effects of cisatracurium may be enhanced by concurrent enflurane or isoflurane (dosage requirements may be decreased by 30–40%; smaller boluses and lower infusion rates may be necessary). Higher infusion rates may be required and duration of action may be shortened in patients receiving long-term carbamazepine or phenytoin.
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IV (Adults and Children >2 yr): 0.4–0.5 mg/kg initially (0.25–0.35 mg/kg if administered after steady-state anesthesia with enflurane or isoflurane or 0.3–0.4 mg/kg following succinylcholine) then may repeat 0.08–0.1 mg/kg 20–45 min after initial dose as needed, or by continuous infusion at 0.4–0.8 mg/kg/hr.
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IV (Neonates, Infants, and Children up to 2 yr): 0.3–0.4 mg/kg initially followed by maintenance doses of 0.3–0.4 mg/kg as needed or 0.6–1.2 mg/kg/hr via continuous infusion.
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IV (Adults and Children >12 yr): Initial intubating dose—0.15–0.2 mg/kg, additional maintenance doses of 0.03 mg/kg may be used 40–65 min later; continuous infusion—1–3 mcg/kg/min.
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IV (Children 2–12 yr): Initial intubating dose—0.1 mg/kg followed by a maintenance dose of 0.03 mg/kg as needed; continuous infusion—1–4 mcg/kg/min.
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IV (Adults and Children >12 yr): 25–50 mcg/kg (may need up to 80 mcg/kg for prolonged effect; 25 mcg/kg for succinylcholine-assisted intubation) initially, followed 60–100 min later by 5–10 mcg/kg, repeated as required or 6–12 mcg/kg/hr via continuous infusion.
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IV (Children 2–12 yr): 30–50 mcg/kg initially; maintenance doses of 5–10 mcg/kg may be required more frequently than in adults or 6–12 mcg/kg/hr via continuous infusion.
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IV (Adults and Children): 1 mg/kg (not to exceed 100 mg/dose), then 0.5–1 mg/kg may be given 30–40 min later if needed during prolonged procedures; dose cautiously in patients <5 kg.
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IV (Adults): 150–400 mcg/kg initially; may give additional doses of 0.5–1 mg q 30–90 min. Adjunct to electroconvulsive therapy—2–3 mg (range 1.75–5.5 mg).
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IV (Adults): 150–200 mcg/kg initially, then 100 mcg/kg as bolus doses every 15 min or as a continuous infusion at 9–10 mcg/kg/min. If infusion is begun at the same time as initial dose, start with rate of 4 mcg/kg/min. Infusion rates may range from 1–20 mcg/kg/min.
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IV (Children 2–12 yr): 200 mcg/kg initially; may be repeated as needed or continued as an infusion at 10–14 mcg/kg/min (range 5–31 mcg/kg/min).
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IV (Adults and Children >12 yr): 0.15 mg/kg initially; repeat doses may be given q 30–60 min to maintain paralysis. Continuous infusion—0.02–0.04 mg/kg/hr.
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IV (Children 1–12 yr): 0.15 mg/kg initially; repeat doses may be given q 30–60 min to maintain paralysis. Continuous infusion—0.03–0.1 mg/kg/hr.
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IV (Neonates and Infants up to 1 yr): 0.1 mg/kg initially; repeat doses may be given q 30–60 min to maintain paralysis. Continuous infusion—0.02–0.04 mg/kg/hr.
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IV (Adults): 70–85 mcg/kg (if given following recovery from succinylcholine during intubation, decrease dose to 50 mcg/kg; 70–85 mcg/kg if longer paralysis desired). Additional doses of 10–15 mcg/kg may be required as maintenance (dosage reduction recommended if using concurrent inhalation anesthetics). Dose should be determined on the basis of ideal body weight in obese patients and may require adjustments in patients with renal impairment.
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IV (Children 1–14 yr): 57 mcg/kg initial dose.
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IV (Infants 3 mo–1 yr): 40 mcg/kg initial dose.
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IV (Adults and Children >12 yr): Rapid sequence tracheal intubation—0.6–1.2 mg/kg; maintenance dosing—0.1–0.2 mg/kg; continuous infusion—10–12 mcg/kg/min (range 4–16 mcg/kg/min).
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IV (Children): Intubation dose—0.6 mg)/kg; maintenance dose— 0.075–0.125 mg/kg; continuous infusion—10–12 mcg/kg/min (range 4–16 mcg/kg/min).
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IV (Infants): 0.5 mg/kg/dose q 20–30 min as needed.
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Preferred route is IV, but IM may be used in infants or other patients without venous access.
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IM, IV (Adults): 6–9 mg initially, followed by 3–4.5 mg after 3–5 min if needed. Additional doses of 3 mg (0.165 mg/kg) may be given as needed. Provision of relaxation to allow mechanical ventilation—1 mg IV (16.5 mcg/kg); subsequent doses may be given as necessary; adjunct to electroconvulsive therapy—165 mcg/kg IV (initial doses should be 3 mg less than calculated dose); diagnosis of myasthenia gravis—4–33 mcg/kg IV. Profound myasthenic symptoms may occur.
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IV (Infants and Children): 500 mcg/kg.
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IV (Neonates–4 wk): 250–500 mcg/kg initially, then additional increments of Display Formula of initial dose may be given.
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IV (Adults and Children >10 yr): Intubation—80–100 mcg/kg for intubation (60–85 mcg/kg if given after steady-state anesthesia achieved or 40–60 mcg/kg after succinylcholine-assisted intubation and anesthesia; wait for disappearance of succinylcholine effects; or 50–60 mcg/kg during balanced anesthesia). Up to 150–280 mcg/kg have been used in some patients; maintenance—10–15 mcg/kg 25–40 min after initial dose, then q 12–15 min as needed or as a continuous infusion at 1.5–2 mcg/kg/min.
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IV (Children >1 yr): 100 mcg/kg q 1 hr as needed or as a continuous infusion of 1.5–2.5 mcg/kg/min.
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IV (Infants >7 wk–1 yr): 100 mcg/kg q 1 hr as needed or as a continuous infusion of 1–1.5 mcg/kg/min.
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IV (Neonates): 100 mcg/kg initially then 30–150 mcg/kg/dose q 1–2 hr as needed.
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Atracurium (generic available)
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Injection: 10 mg/mL in 5-mL ampules and 10-mL vials.
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Solution for injection: 2 mg/mL in 5-mL single-use vials or 10-mL multiple-dose vials (with benzyl alcohol), 10 mg/mL in 20 mL vials Rx.
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Injection: 1 mg/mL in 5-mL vials.
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Injection: 20 mg/mL in 10-mL vials.
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Metocurine (generic available)
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Injection: 2 mg/mL in 20-mL vials.
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Injection: 0.5 mg/mL premixed infusion in 50 mL D5W, 2 mg/mL in 5- and 10-mL vials.
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Injection: 1 mg/mL in 10-mL vials, 2 mg/mL in 2- and 5-mL ampules.
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Powder for injection: 10 mg/vial.
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Injection: 10 mg/mL in 5-mL vials.
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Tubocurarine (generic available)
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Injection: 3 mg (20 units)/min 10- and 20-mL vials and 5-mL syringes.
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Powder for injection: 10 mg and 20 mg vials.