CLASS
Anticholinesterase
PRESENTATION
Clear, colourless solution in transparent ampoule.
Formulations
- 2.5mg in 1ml
INDICATIONS & DOSING
Reversal of non-depolarising neuromuscular blockade
- Adult; 2.5mg IV, max 5mg
- Paed; 50mcg/kg IV, max 2.5mg
Prophylaxis of postoperative gastrointestinal atony, urinary retention
- Adult; 0.25-0.5mg IM/SC, pre/intraoperatively followed by Q4-6h for 2-3 days
PRACTICALITIES
Administration
- 2.5mg neostigmine is administered in combination with 400mcg glycopyrrolate to offset non-neuromuscular muscarinic effects
Incompatibilities
- Nil significant
Practice tips
- Use as a reversal agent should not be attempted until some degree of spontaneous recovery is evident (TOF count >1)
- The speed of reversal of neuromuscular blockade is mainly determined by the depth of neuromuscular blockade prior to administration
- Neuromuscular monitoring is recommended to confirm reversal of paralysis due to multitude of other factors that may augment effect of neuromuscular blockers
- Administration may complicate management of those with myasthenia gravis on cholinergic treatment (variable response, precipitation of cholinergic crisis), consider use of sugammadex instead
PHARMACOKINETICS
Onset
- IV; ~5-15 minutes
Duration of action
- 40-60 minutes following bolus dose
Metabolism
Majority hepatic, hydrolysis of ester linkages and metabolism by microsomal enzymes
Elimination
Renally excreted, 50% unchanged, 50% as metabolites of parent molecule
MECHANISM
Reversible inhibition of acetylcholine hydrolysis by competition for attachment to acetylcholinesterase increases nerve terminal acetylcholine concentrations, augmenting neuromuscular transmission
DESIRED CLINICAL EFFECTS
Neuromuscular
- Reversal of neuromuscular blockade and paralysis
OTHER CLINICAL EFFECTS, ADVERSE EFFECTS & TOXICITIES
Respiratory
- Increased airway secretions
- Bronchospasm
- Respiratory depression/arrest (overdose)
Cardiovascular
- Bradycardia, reduced cardiac output, hypotension/cardiac arrest
- Bradyarrhythmia
Neurological
- Headache, vertigo, restlessness
- Agitation, slurred speech, ataxia seizures, drowsiness/coma (overdose)
Neuromuscular
- Fasciculations, cramps
- Generalised weakness, paralysis (overdose)
Renal & electrolytes
- Urinary incontinence
Gastrointestinal
- Nausea/vomiting, abdominal cramps, diarrhoea
- Faecal incontinence
Other
- Sweating, salivation
- Miosis, diplopia, nystagmus, lacrimation
- Precipitation of cholinergic crisis
Antidote
- Atropine, glycopyrrolate
CONSIDERATIONS
Precautions
- Bronchospastic disease
- Mechanical intestinal or urinary tract obstruction, recent gastrointestinal surgery, recent bladder surgery
- Cardiovascular compromise; hypotension/shock states, coronary ischaemia, bradycardia/conduction defects
Obstetric
Category B2; may increase uterine irritability and induce premature labour in late gestation
Drug interactions
- Suxamethonium; prolongation of phase 1 block
- Anaesthetics agents, sodium channel blockers, lithium, calcium channel blockers, aminoglycoside antibiotics; diminished efficacy
REFERENCES
Drug information has been compiled from multiple sources including
- Drugs in Anaesthesia and Intensive Care (Scarth & Smith)
- Micromedex (IBM)
- BJA Education (Oxford Academic)
- Pharmacology for Anaesthesia and Intensive Care (Cambridge)
- Australian Prescriber (NPS MedicineWise)
- Clinical experience of authors