reversal of neuromuscular blockade 11-05ds

8/3/2019 Reversal of Neuromuscular Blockade 11-05ds

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REVERSAL OF NEUROMUSCULAR BLOCKADE

DENNIS STEVENS MSN, CRNA, ARNPNOVEMBER 2005

FLORIDA INTERNATIONAL UNIVERSITYPHARMACOLOGY: NGR 6173


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OBJECTIVES Explain the mechanism of action of commonly

administered neuromuscular reversal agents.

Discuss the clinical pharmacologic characteristics

associated with cholinesterase inhibitors. Compare the effects that neuromuscular reversal agents

have on organ systems.

State the dosage recommendations for medications

associated with the reversal of neuromuscular blockade. Discuss how organ systems are affected by

anticholinergic agents.


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REFERENCES

Morgan, G.E., Mikhail, M.S., and Murray, M.J. (2002).Clinical Anesthesiology. (3rd Ed.). New York, NY:McGraw-Hill.

Nagelhout, J.J. and Naglaniczny, K.L. (2005). NurseAnesthesia. (3rd Ed.). St. Louis, MO: Elsevier-Saunders.

Stoelting, R.K. (1999). Pharmacology & Physiology inAnesthesia Practice. (3rd Ed.). Philadelphia, PA:

J.B. Lippincott Company.


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INTRODUCTION Cholinesterase inhibitors (anticholinesterases) are used

to reverse the effects of nondepolarizing neuromuscularblockers

Facilitates the speed of recovery from the skeletalmuscle effects associated with NDMRs Physostigmine is the prototype Derived from the Calabar bean Once used by West African tribes as a poison 1864: physostigmine isolated by Jobst and Hesse Precursor of organophosphates:

Insecticides

Nerve gas


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INTRODUCTION Commonly used cholinesterase inhibitors:

Neostigmine Edrophonium Pyridostigmine Physostigmine

Cholinergic receptors Nicotinic receptors Muscarinic receptors

Primary goal of muscle relaxant reversal is to maximizenicotinic transmission while minimizing muscarinic side

effects


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MECHANISM OF ACTION Neuromuscular transmission depends on acetylcholine

NDMRs compete with acetylcholine thereby blockingneuromuscular transmission

Reversal of blockade depends on gradual diffusion,redistribution, metabolism, and excretion of the NDMR

Pharmacologic reversal with administration of specificcholinesterase inhibitor agents

Neostigmine, pyridostigmine, and edrophonium inhibitsacetylcholinesterase which is responsible for the rapidhydrolysis of the neurotransmitter acetylcholine tocholine and acetic acid


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MECHANISM OF ACTION Inhibition of the hydrolysis of acetylcholine results in

greater availability at its sites of action

Pharmacological effects:

Competitive block at NMJ Inhibition of acetylcholinesterase Acceleration of the already established pattern of

spontaneous recovery Speeds time of recovery and allows for more prompt

wake up and recovery of protective reflexes

Administered during the time when spontaneousrecovery from neuromuscular blockade is occurring


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CLINICAL PHARMACOLOGICCHARACTERISTICS

Cholinesterase inhibitors can act at cholinergicreceptors of several other organ systems

Cardiovascular: Decreased heart rate Dysrhythmias

Pulmonary: Bronchospasm Increased bronchial secretions

Cerebral: Diffuse excitation


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CLINICAL PHARMACOLOGICCHARACTERISTICS

Gastrointestinal: Increased peristaltic activity Glandular secretions

Genitourinary: Increased bladder tone

Ophthalmologic:

Pupillary constriction Reversal of NDMR blockade requires only the nicotinic

cholinergic effects of the anticholinesterase drug.Muscarinic effects are attenuated or prevented by theconcurrent administration of anticholinergic agents


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NEOSTIGMINE Quaternary ammonium compound

Lipid insoluble; will not cross the blood-brain barrier

Two-fold mechanism of reversal: Inactivation of acetylcholinesterase Increase half life of acetylcholine at receptors

Dose: Maximum recommended dose 0.08 mg/Kg Dose should never exceed 5 mg


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NEOSTIGMINE Onset: 5-10 minutes Duration: 45-90 minutes Recommended anticholinergic: glycopyrrolate

Reported to cross placenta resulting in fetal bradycardia Most commonly used reversal agent; may increase

incidence of PONV May be used to treat myasthenia gravis, urinary bladder

atony, and paralytic ileus Has been used as an adjunct to intrathecal anesthesia Pediatric and elderly patients appear to be more sensitive

to its effects


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EDROPHONIUM Quaternary ammonium compound

Limited lipid solubility

Available with atropine as a combination drug (Enlon-Plus)

Dose: 0.5-1.0 mg/Kg

Most rapid onset of action; within 5 minutes

Duration: 30-60 minutes Recommended anticholinergic: atropine

Not recommended for deep block


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PYRIDOSTIGMINE Used in the treatment of myasthenia gravis

Long acting acetylcholinesterase inhibitor

Dose: 0.1-0.4 mg/kg

Slow onset: 10-20 minutes

Duration: 60-120 minutes

Recommended anticholinergic: glycopyrrolate

Not frequently used in anesthesia


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PHYSOSTIGMINE Tertiary amine

Lipid-soluble and freely passes the blood-brain barrier

Can cause confusion and lethargy

Used to counteract the delirium caused bybenzodiazepines and barbiturates

Dose: 0.01-0.03 mg/Kg


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COMPETETIVE BLOCKADE Competition between NDMR and acetylcholine for the

motor end plate receptor at the neuromuscular junction

Greater concentration gains control of the receptor site

Recurarization was a problem with long acting NDMRs

whose effects outlasted the clinical effects of theanticholinesterase agents


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ELIMINATION All acetylcholinesterase inhibitors are excreted to some

extent by the kidneys

Neostigmine: 25% Edrophonium: 75%

Elimination half-life of neostigmine:

70-80 minutes in patients with normal renal function 181 minutes in anephric patients


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ANTICHOLINERGICS Glycopyrrolate

Atropine

Scopolamine Anticholinergics are esters of an aromatic acid

combined with an organic base In clinical doses only muscarinic receptors are blocked Administered to attenuate the peripheral muscarinic

effects of acetylcholinesterase inhibitors Acetylcholinesterase inhibitors must be administered

with an anticholinergic Several organ systems are affected


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SYSTEMIC EFFECTS Cardiovascular:

Blockade of muscarinic receptors in the SA node resultsin increased heart rate

Atrial dysrhythmias and nodal rhythms occasionally occur Respiratory:

Inhibits secretions of the respiratory tract mucosa Relaxes bronchial smooth musculature

Cerebral: Can cause various CNS effects ranging from stimulation

to depression Physostigmine reverses these actions


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SYSTEMIC EFFECTS Gastrointestinal:

Salivary secretions markedly reduced

Prolonged gastric emptying time Ophthalmic:

Causes mydriasis and cyclopegia

Genitourinary:

May decrease ureter and bladder tone Thermoregulation:

Inhibition of sweat glands


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PHARMACOLOGIC CHARACTERISTICS

Naturally occurring tertiary amine anticholinergic drugs:

Atropine and scopolamine

Semisynthetic quaternary ammonium derivative: Glycopyrrolate


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DOSAGE RECOMMENDATIONS Neostigmine 0.5-0.8 mg/Kg with equal portion of

glycopyrrolate (0.2 mg glycopyrrolate per 1mgneostigmine). Maximum dose neostigmine 5 mg.

Edrophonium 0.5-1 mg/Kg with atropine 0.014 mg per1 mg of edrophonium. If glycopyrrolate administered(0.007 mg glycopyrrolate per 1 mg of edrophonium)should be given several minutes prior to edrophonium

to avoid bradycardia. When administering reversal agents to pediatric

patients, always give the anticholinergic, wait for aresponse, then give the acetylcholinesterase inhibitor.

reversal of neuromuscular blockade 11-05ds

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