Details About Overdose or Poisoning Generic Salt ::  Neuromuscular Blockers

Neuromuscular Blockers

    

Drug Pharmacology ::

I. Pharmacology./b>

   

Neuromuscularblocking agents produce skeletal muscle paralysis by inhibiting theaction of acetylcholine at the neuromuscular junction. Depolarizing agents(eg, succinylcholine; Table III–11) depolarize the motor end plate andblock recovery; transient muscle fasciculations occur with the initialdepolarization. Nondepolarizing agents (atracurium,pancuronium, and others; Table III–11) are classified as either abenzylisoquinolinium diester (eg, mivacurium, atracurium) or anaminosteroid (eg, vecuronium, rocuronium) and competitively block theaction of acetylcholine at the motor end plate; therefore, no initialmuscle fasciculations occur. They also block acetylcholine atsympathetic ganglia, and this may result in hypotension.

Theneuromuscular blockers produce complete muscle paralysis with nodepression of CNS function (they are positively charged andwater-soluble compounds that do not cross the brain-blood barrierrapidly). Thus, patients who are conscious will remain awake but unableto move and patients with status epilepticus may continue to have CNSseizure activity despite flaccid paralysis. Furthermore, theneuromuscular blockers do not relieve pain or anxiety.

Succinylcholineproduces the most rapid onset of effects, with total paralysis within30–60 seconds after intravenous administration. It is hydrolyzedrapidly by plasma cholinesterases, and its effects dissipate in 10–20minutes. Rocuronium, a nondepolarizing agent, also offers a rapid onsetfor rapid-sequence intubations. Onset and duration of several otherneuromuscular blockers are described in Table III–11.

Drug Indications ::

Indications

   

Neuromuscularblockers are used to abolish excessive muscular activity, rigidity, orperipheral seizure activity when continued hyperactivity may produce oraggravate rhabdomyolysis and hyperthermia. Examples of such situationsinclude the following. Note: The preferred agent for these conditions is a nondepolarizing agent.

   

1. Drug overdoses involving stimulants (eg, amphetamines, cocaine, phencyclidine, monoamine oxidase inhibitors) or strychnine.

2. Tetanus.

3. Hyperthermiaassociated with muscle rigidity or hyperactivity (eg, statusepilepticus, neuroleptic malignant syndrome, or serotonin syndrome; seeHyperthermia). Note: Neuromuscular blockers are noteffective for malignant hyperthermia (see Malignant hyperthermia); infact, inability to induce paralysis with these agents should suggestthe diagnosis of malignant hyperthermia.

Neuromuscularblockers provide prompt flaccid paralysis to facilitate orotrachealintubation. The preferred agents for this purpose are rapid-onsetagents such as succinylcholine, rapacurium, mivacurium, rocuronium, andvecuronium. They also are used to treat laryngospasm.

Drug Contra-Indications ::

III. Contraindications./b>

   

Lackof preparedness or inability to intubate the trachea and ventilate thepatient after total paralysis ensues. Proper equipment and trainedpersonnel must be assembled before the drug is given.

Knownhistory of malignant hyperthermia. Succinylcholine use is associatedwith malignant hyperthermia in susceptible patients (incidence,approximately 1 in 50,000 in adults and 1 in 10,000 in children).

Knownhypersensitivity or anaphylactic reaction (non-dose-related) to agentor preservative (eg, benzyl alcohol). Succinylcholine is implicatedmost commonly, but anaphylaxis has been reported with rocuronium,atracurium, mivacurium, and cisatracurium.

Known history of or at high risk for succinylcholine-induced hyperkalemia. (See IV.D. below.)

Drug Adverse Effects ::

IV. Adverse effects

   

Complete paralysis results in respiratory depression and apnea.

Succinylcholinecan stimulate vagal nerves, resulting in sinus bradycardia and AVblock. Children are particularly sensitive to vagotonic effects (canprevent with atropine).

Musclefasciculations may cause increased intraocular and intragastricpressure (the latter may result in emesis and aspiration of gastriccontents). Rhabdomyolysis and myoglobinuria may be observed, especiallyin children.

Succinylcholinemay produce hyperkalemia in patients with neuropathy, myopathy, recentsevere burns, or head and spinal cord injury (this risk is maximal afew months after the injury). There is one case report of a patientwith wound botulism. The mechanism is increased extrajunctional muscleacetylcholine receptors and may also occur with prolonged use ofnondepolarizing agents.

E. Clinicallysignificant histamine release with bronchospasm may occur, especiallywith succinylcholine, mivacurium, and rapacuronium (which was withdrawnfrom the market). It is more common with smokers and patients withreversible airway disease.

F. Neuromuscularblockade is potentiated by hypokalemia and hypocalcemia(nondepolarizing agents) and by hypermagnesemia (depolarizing andnondepolarizing agents).

G. Prolonged effects may occur after succinylcholine use in patients with genetic deficiency of plasma cholinesterase.

H. Prolongedeffects may occur in patients with neuromuscular disease (eg,myasthenia gravis, Eaton-Lambert syndrome) or resistance (eg,myasthenia gravis and succinylcholine).

Tachycardia caused by vagal block and sympathomimetic effects from pancuronium and high-dose rocuronium.

J. Neuropathies, myopathies, and persistent muscular weakness associated with prolonged use owing to chemical denervation.

K. Use in pregnancy. FDA category C (indeterminate). This does not preclude their acute, short-term use in a seriously ill patient (see Table III–1).

Drug Lab Interactions ::

Drug or laboratory interactions

   

Actionsof the nondepolarizing agents are potentiated by ether, methoxyflurane,and enflurane and are inhibited or reversed by anticholinesteraseagents (eg, neostigmine, physostigmine, and carbamate andorganophosphate insecticides).

Organophosphateor carbamate (see Organophosphorus and Carbamate Insecticides)insecticide intoxication may potentiate or prolong the effect ofsuccinylcholine.

Numerousdrugs may potentiate neuromuscular blockade. These drugs includecalcium antagonists, dantrolene, aminoglycoside antibiotics,propranolol, membrane-stabilizing drugs (eg, quinidine), magnesium,lithium, and thiazide diuretics.

Anticonvulsants(carbamazepine and phenytoin) and theophylline may delay the onset andshorten the duration of action of some nondepolarizing agents.Carbamazepine has additive effects, and reduction of the neuromuscularblocker dose may be required.

E. Dysrhythmias are possible with myocardial sensitizers (eg, halothane) and sympathetic stimulating agents (eg, pancuronium).

Drug Dose Management ::

Dosage and method of administration (see Table III–11)

Drug Chemical Formulations ::

Formulations

   

Succinylcholine chloride (Anectine®and others), 20 and 50 mg/mL; 10-mL vials (with parabens and benzylalcohol) and ampules; 100 mg in 5-mL syringe; 500 mg and 1 g (powderfor infusion). The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is two vials of each concentration.

Atracurium besylate (Tracrium), 10 mg/mL in 5-mL single-dose and 10-mL multidose vials (with benzyl alcohol). The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is four 10-mL vials.

Cisatracurium besylate (Nimbex), 2 mg/mL in 5- and 10-mL vials; 10 mg/mL in 20-mL vials (with benzyl alcohol). The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is one 20-mL vial or the equivalent.

Pancuronium bromide (Pavulon, others), 1 and 2 mg/mL in 2-, 5-, and 10-mL vials, ampules (some with benzyl alcohol), and syringes. The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is eight vials (2 mg/mL, 5 mL each).

E. Rocuronium bromide (Zemuron), 10 mg/mL in 5- and 10-mL vials. The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is seven vials.

F. Vecuronium bromide(Norcuron, others), 10-mg and 20-mg vials of lyophilized powder forreconstitution (Norcuron contains mannitol, and diluent may containbenzyl alcohol). The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is three vials.

G. Doxacurium chloride (Nuromax), 1 mg/mL in 5-mL vials (with benzyl alcohol). The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is three vials.

H. Pipecuronium bromide (Arduan) 10 mg in 10-mL vials (powder for injection). The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is two vials.

Mivacurium chloride (Mivacron) 0.5 mg/mL and 2 mg/mL in 5- and 10-mL single-use vials. The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is four 10-mL vials or the equivalent.

Table III–11. Selected Neuromuscular Blockers


Drug Onset Durationa Dose (all are intravenous) Depolarizing      Succinylcholine0.5–1 min2–3 min0.6 mg/kgb (children: 1 mg/kgc) over 10–20 seconds; repeat as needed. 
 Nondepolarizing      Atracurium3–5 min20–45 min0.4–0.5 mg/kg (children < 2 years: 0.3–0.4 mg/kg).  Cisatracurium1.5–2 min55–61 min0.15–0.2 mg/kg (children 2–12 years: 0.1 mg/kg), then 1–3 mcg/kg/min to maintain blockade.  Pancuronium2–3 min35–45 min0.06–0.1 mg/kg; then 0.01–0.02 mg/kg every 20–40 min as needed to maintain blockade.  Rocuronium0.5–3 min22–94 min0.6–1 mg/kg; then 0.01 mg/kg/min to maintain blockade.  Vecuronium1–2 min25–40 minFor children > 1 year and adults: 0.08–0.1 mg/kg bolus, then 0.01–0.02 mg/kg every 10–20 min to maintain blockade.  Doxacurium5–7 min56–160 min0.05–0.08mg/kg (children 0.03–0.05 mg/kg), then 0.005–0.01 mg/kg every 30–45 minto maintain blockade (children may require more frequent dosing).  Pipecuronium3–5 min17–175 min0.05–0.1mg/kg (adjust for renal function); then 0.01–0.015 mg/kg every 17–175min (children may be less sensitive and require more frequent dosing).  Mivacurium2–4 min13–23 min0.15–0.25mg/kg (children 0.2 mg/kg), then 0.1 mg/kg every 15 min, or bycontinuous infusion and start with 0.01 mg/kg/min and maintain withaverage adult dose of 0.006–0.007 mg/kg/min (children 0.014 mg/kg/min).

aFormost agents, onset and duration are dose- and age-dependent. Withsuccinylcholine or mivacurium, effects may be prolonged in patients whohave genetic plasma cholinesterase deficiency or organophosphateintoxication.

bToprevent fasciculations, administer a small dose of a nondepolarizingagent (eg, pancuronium, 0.01 mg/kg) 2–3 min before the succinylcholine.

cPretreat children with atropine at 0.005–0.01 mg/kg to prevent bradycardia or atrioventricular block.

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