Overview
NMBAs facilitate intubation, mechanical ventilation, and surgical relaxation.
Categories of NMBAs
| Category | Examples |
|---|---|
| Depolarizing | Succinylcholine |
| Non-depolarizing | Atracurium, Cisatracurium, Rocuronium, Vecuronium |
| Agent | ED 95 (mg/kg) | Intubating Dose (mg/kg) | Onset (min | Duration to 25% recovery (min) | Intra-op maintenance | Metabolism and Excretion |
|---|---|---|---|---|---|---|
| Succinylcholine | 0.3 | 1 | 1 – 1.5 min | 6 – 8 min | Rarely done | Plasma cholinesterase |
| Rocuronium | 0.3 | 0.6 (RSI 1.2) | 1.5 – 2 (RSI 1) | 30 – 40 (RSI > 60) | 0.1 – 2 mg/kg PRN | > 70% metabolized in liver. Excreted in bile + urine |
| Vecuronium | 0.05 | 0.1 – 0.2 | 3 – 4 | 35 – 45 | 0.01 0 0.02 mg/kg PRN | 50% Liver, Bile + Urine |
| Cisatracurium | 0.05 | 0.15 – 0.2 | 5 – 7 | 35 – 45 | 0.3 mg/kg q 20min PRN | Hoffman elimination |
Depolarizing NMBA
Succinylcholine
Succinylcholine is a very fast-acting depolarizing neuromuscular blocking agent. It consists of 2 ACh molecules joined together by a methyl group. It is a Nicotinic ACh Receptor agonist that causes prolonged depolarization (uncoordinated contractions and relaxations). Its action is terminated via diffusion from the NMJ and rapid metabolization by plasma cholinesterase (pseudocholinesterase)
Intubation dose: 1-1.5 mg
Onset: 30-60 seconds
Duration: 10 minutes (depending on the dose)
- Contraindications to succinylcholine
- Hyperkalemia → cardiac arrest: Induction dose raises serum K+ by 0.5 mEq/L. Normokalemic ESRD is not a contraindication.
- Conditions that upregulate junctional and extrajunctional AChR → Hyperkalemia: Burn injury > 24 hours, muscular dystrophy, myotonias, prolonged immobility, upper motor neuron disease (stroke, spinal cord injury, tumor, multiple sclerosis, Gullain Barre Syndrome)
- History of malignant hyperthermia
- Open globe (anterior camber): causes transient increase in Intraocular pressure
- Side effects
- Fasciculations: decreased with a defasculating dose of rocuronium (0.03 mg/kg, 3 minutes prior)
- Myalgia: more frequent in women and ambulatory patients. Less frequent in children, ages 50-60 yo and those with good muscular training
- Bradycardia: especially in children (has to be given with atropine)
- Tachycarida
- Anaphylaxis: 1:5000 – 1:10,000
- Trismus
- Raised intracellular pressure and intraocular pressure
- Increased intragastric pressure and lower esophageal sphincter pressure
Non-depolarizing NMBA
Non-depolarizing NMBAs are competitive inhibitors of nAChR. They also block the presynaptic nAChR (responsible for mobilizing ACh-containing vesicles). There exists an “autonomic margin of safety” since N=they may interact with sympathetic and parasympathetic (nicotinic and muscarinic) receptors when given at a higher dose. Recovery of neuromuscular blockade occurs primarily because of distribution after initial dose. For repeat or large doses, recovery mainly depends on elimination. Vecuronium is excreted renally and has an active 3-OH metabolite which can accumulate in renal failure (Rocuronium however does not have)
Commonly uses non-depolarizing agents have an intermediate duration: Rocuronium, Cisatracurium, Vecuronium
Classification
| Classification | Effects | Examples |
|---|---|---|
| Benzylisoquinolinium (’-urium’) | More likely to cause histamine release. Can attenuate with slower administration | Cisatracurium, Doxacurium, Atracurium, Mivacurium, d-Tubocurarine |
| Aminosteroid (’-onium) | Vagolytic effects | Pancuronium, Vecuronium, Rocuronium, Pipecuronium |
- Though slower with a longer duration, which non-depolarizing NMBA can be used in place of succinylcholine for RSI?
- Rocuronium (1-1.2 mg/kg) – it has a lower molar potency (requiring a larger dose) and in effect has a faster onset (it equilibrates faster between plasma and the neuromuscular junction
- What is the effect of a priming dose of non-depolarizing NMBA?
- Increases the speed of onset. Given as 10% of the intubating dose 3-5 minutes prior
Reversal
Acetylcholinesterase inhibitors
Reversal of non-depolarizing NMBA can be done using acetylcholinesterase inhibitors – inhibition of acetylcholinesterase → more ACh in the NMJ → overcomes competitive inhibition of non-depolarizing NMBA → muscle firing. The patient should have spontaneous recovery before (2 twitches before reversal). Acetylcholinesterase inhibitors are paired with anticholinergic to prevent muscarinic vagal side effects (bradycardia, GI stimulation, bronchospasm). They are paired based on the speed of onset to appropriately block the muscarinic effect
Pairing of acetylcholinesterase inhibitors with anticholinergics
| Speed of onset | Acetylcholinesterase inhibitor | Anticholinergic |
|---|---|---|
| Rapid | Edrophonium | Atropine |
| Intermediate | Neostigmine | Glycopyrrolate |
| Slow | Pyridostigmine | Glycopyrrolate |
- Acetylcholinesterase inhibitors
- Neostigmine, Pyridostigmine, Edrophonium: Do NOT cross the BBB
- Physostigmine: crosses the BBB, can treat central anticholinergic/atropine toxicity
- Does the reversal of non-depolarizing NMBA increase the risk of PONV?
- No (Cheng CR, 2005)
Sugammadex
y-cyclodextrin directly binds to and traps rocuronium (and vecuronium).
Recommended dose of sugammadex
| Indication | Recommended dose |
|---|---|
| Cannot intubate, cannot ventilate | 16 mg/kg |
| Deep reversal | 4 mg/kg |
| Standard reversal | 2 mg/kg |
- Indications for using sugammadex
- Cannot intubate, cannot ventilate after rocuronium 1.2 mg/kg (Sugammadex 16mg/kg can decrease time to full recovery from 122 minutes to < 2 minutes)
- Blockade to deep or inadequately reversed by neostigmine
- During pregnancy (unlike neostigmine, sugammadex does not cross the placent)
- Benefits of using sugammadex as a routine reversal agent
- Less side effects, faster onset and cheaper than neostigmine + glycopyrrolate
- Reversal reduces the risk of post-op pulmonary complications
- What precautions should be taken when sugammadex is used for reversal?
- Patients using hormonal contraceptive must use an additional non-hormonal method for the next 7 days
- Not recommended for severe renal insufficiency or dalysis (theoretically the complex formed can be dissociated by hemodialyzer)
- PTT and PT will be prolonged by 25% up to 60 minutes
- Precipitates with ondansetron, verapamil, or ranitidine
- Anaphylaxis in 0.3%
Effects of Clinical Conditions on Action of NMBA
- Conditions with nAChR upregulation (Sensitive to Succinylcholine, Resistant to NMBA)
- Spinal cord injury
- Stroke
- Burns
- Prolonged immobility
- Prolonged exposure to NMBA
- Multiple sclerosis
- Guillain-Barre syndrome
- Conditions with nAChR downregulation (Resistant to succinylcholine, sensitive to NMBA)
- Myasthenia gravis
- Lamber-Eaton syndrome
- Anticholinesterase poisoning
- Organophosphate poisoning
- Factors that enhance block by NMBA
- Volatile anaesthetics
- Aminoglycosydes, Tetracycline, Clindamycin
- Magnesium
- IV Local anaesthetics
- Calcium cannel blockers
- Furosemide
- Dantrolene
- Lithium
- Anticonvulsants
- Succinylcholine
- Acidosis
- Hypokalemia
- Hypothermia
- Ketamine
- Common surgeries to avoid NMBA
- Axillary node dissection
- ENT cases near nerves
- Neuromonitoring
| Condition | AChR | Depolarizing NMBA | Non-depolarizing NMBA | Nota Bene |
|---|---|---|---|---|
| Stroke | Upregulated | Do not use after 24 hours | – | Succinylcholine may cause hyperkalemia months after the stroke |
| Burns | Upregulated | Do not use after 24-48 hours | Recovery of neuromuscular function to pre-burn level may take months to years | |
| Prolonged immobility | Up-regulation | Caution, | Risk of reaction significantly increases after 16 days | |
| Multiple sclerosis | Up-regulation | Caution | May have resistance or sensitivity | |
| Amyotrophic lateral sclerosis (ALS) | Up-regulation | High risk of hyperkalemia | Sensitive | |
| Guillain-Barre | Up-regulation | Contraindicated | Sensitive | Risk of hyperkalemia may persist after symptomatic revovery |