Neuromuscle Relaxants and Reversal Agents.pptx

Neuromuscle Relaxants and Reversal Agents.pptx

1. Muscle Relaxants & Reversal Agents Supervisor Dr Brian R Presenter Dr Shinnie

2. Outline Neuromuscular junction physiology Indication for Muscle relaxant Mechanism Of Action - Depolarising Agent and Non Depolarizing Agents Pharmacology and Pharmacokinetics of Muscle Relaxant Adverse reactions of muscle relaxants Reversal agents Pharmacology of Reversal agents Neuromuscular monitoring

3. Acetylcholinesterase (AchE) is found in junctional clefts. Neuromuscular junction physiology

4. Action Potential Arrive lead to Ca+ influx Release of Ach Bind to Ach Receptor resulting Na+ influx Rapid Depolarization leading action potential to cross the muscle surface Contraction of Skeletal Muscle Ach hydrolysis by AchE leading to repolarization Muscle is ready for new contraction

5. Indication for Muscle relaxants Facilitate muscle relaxation for intubation Optimize surgical working conditions Mechanical ventilation during surgery or in ICU

6. Mechanism Of Action - Depolarising Agent and Non Depolarizing Agents Depolarizing Agent - Mimic the action of Ach (Agonists) - eg: Suxamethonium Phase 1 Phase 2 Desensitising Muscle Fasciculation Muscle Flaccid Depolarising Pseudocholinesterase (PCHE) is present in serum, plasma, liver, pancreas, heart, and other tissues .

7. Non Depolarizing Agents - Interferes with the action of Ach (Antagonist) - eg: Rocuronium, Atracurium 2 Ach are required for transmission of impulse Only 1 molecule of NDB is required for blockade of impulse transmission By blocking the binding of ACh so the motor endplate cannot depolarize. This leads to muscle paralysis. No Depolarization Occurs

8. Pharmacology of Muscle Relaxants Suxamethonium Atracurium Rocuronium Intubating Dose 1-1.5mg/kg Max dose 150mg 0.5mg/kg 0.6mg/kg 1 Vial 100mg in 2ml 25mg in 2.5ml 50mg in 5ml RSI 1-1.5mg/kg - 1-1.2mg/kg Onset - 90-120s 60-90s DOA 3-5min 20-35min 20-35min Maintenance non depolarizing agents ⅕ to ¼ of intubating dose ⅕ to ¼ of intubating dose

9. Pharmacokinetics Suxamethonium Atracurium Rocuronium Metabolized Hydrolysed plasma pseudocholinesterase Not depend on organ/ plasma pseudocholinesterase Liver Excreted Non specific esterase hydrolysis or Hofmann Elimination - Spontaneous breakdown to Laudanosine kidney

10. Adverse reactions of Suxamethonium CVS - Sinus Bradycardia, Ventricular arrhythmias due to stimulation of muscarinic receptors CNS - Increase ICP due to stimulation of muscle Fasiculation GI - Increase intragastric pressure due to fasciculation Hyperkalemia - sustained ion channel opening due to K leak Myalgia - commonest in young female due to unsynchronised muscle facciculation Ophtha - Increase IOP due to contraction of tonic myofibrils Other - Anaphylaxis, Malignant Hyperthermia, Prolonged neuromuscular block Succinycholine apnoea

11. Muscle Fasciculation Depolarization Myalgia post operatively Transient Increase ICP Transient Increase IOP Transient Increase IGP Hyperkalemia Direct Effect to heart Sinus Bradycardia Ventricular arrhythmias Cardiac Arrest Anaphylaxis Succinylcholine apnoea Malignant Hyperthermia Proliferation Of Extra-junctional Ach receptors in damaged tissues

12. Malignant hyperthermia (MH) Anesthesia Emergency resulting from a disproportionate increase in muscle activity on exposure to volatile anesthetic agents and succinylcholine. ATP depletion the demand for adenosine triphosphate (ATP) exceeds maximal rates of mitochondrial production. Increase in muscle activity MH reaction causes an increase in muscle activity, carbon dioxide production, oxygen consumption, production of heat. Intense sympathetic stimulation Intense sympathetic stimulation causing progressive tachycardia and respiratory acidosis.

13. Rise Tempurature Liberated cellular constituents and increased temperature may cause disseminated intravascular coagulation. Anaerobic glycolysis Increases hydrogen ion and lactate production. loss of cell membrane integrity Leading to hyperkalemia, a rise in creatine kinase (CK) concentration, myoglobinuria, renal failure, cardiac arrhythmias, and death.

14. Recovery Bay (Blue Trolley)

15. MAINTENANCE OF ANAESTHESIA Consider Propofol maintenance +/- benzodiazepine HYPERKALAEMIA MANAGEMENT Insulin 10 units + 50 ml D50% + Calcium Gluconate 20% Hyperventilate High Flow 100% O2 with Ambu bagging Call senior surgeon If required to complete surgery rapidly Convert GXM FFP/cryoprecipitate/platelets

16. Call for help Bring in the MH Trolley Off Volatile Agent Hyperventilate + High Flow 100% O2 by Ambu bagging Off Warmer Ask surgeon the stage of surgery - Close abdomen and to plan definitive op later Give Bolus IV Midazolam to keep patient sedated while waiting TIVA Prepare TIVA - for closure Active Cooling with Iced Saline, Gastric lavage with iced saline or surface cooling Prepare Dantrolene 2.5mg/Kg Bolus STAT Convert FFP/cryoprecipitate/platelets Monitor Urine Output Send blood : ABG/FBC/RP/Coag Profile/CK For ICU admission to close monitoring

17. Adverse reactions of Atracurium CVS - Histamine Release causes increase in HR and Hypotension CNS - No Effect GI - No Effect RSP - Bronchospasm Anaphylaxis - 2nd Highest risk of anaphylaxis

18. Adverse reactions of Rocuronium CVS - Minimal CVS effect but with large dose leads to slight vagolysis CNS - No Effect GI - No Effect RSP - No Effect Anaphylaxis - Highest risk of Anaphylaxis of all NMBD despite itself not release histamine

19. Reversal agents Neostigmine AchE antagonist, Not Cross BBB Slowing the effect of hydrolysis of Ach so that more Ach in NMJ Indirectly stimulate Muscarinic receptors Use along with antimuscarinic agent like glycopyrrolate or atropine to attenuate the parasympathomimetic activity

20. Adverse Effects of Neostigmine Bradycardia All blood Vessels are dilated, resulting falling BP Smooth muscle contracted, increase Tone & Peristalsis Bronchial muscle constrict, Bronchospasm Paradoxical anticholinesterase associated muscle weakness

21. Atropine Anticholinergic drug Cross BBB Competitive antagonism of acetylcholine at muscarinic receptors Bronchodilation and bronchial secretions reduces Counter bradycardia Reduces salivation, gastric secretions, tone, peristalsis Less Sedative Metabolized in Liver Excreted in Kidney

22. Glycopyrrolate Bronchodilation and bronchial secretions reduces Counter bradycardia Reduces salivation, the volume of gastric secretions, and tone and peristalsis Anticholinergic drug NOT Cross BBB Competitive antagonism of acetylcholine at muscarinic receptors Metabolized in Liver Excreted in Kidney

23. Sugammadex Sugammadex is used for reversal of the aminosteroid NMBD: Rocuronium, vecuronium Encapsulated aminosteroid NMBD - plasma concentrations decrease - Creating gradient that pull NMBD from tissues to plasma Sugammadex can be titrated in theatre with the use of TOF 2mg.kg -1 if ToF > 2. 4mg.kg -1 if PTC > 2. 16mg.kg -1 for reversal following RSI dose.

24. Neuromuscular monitoring

25. Train of Four (TOF) Stimulation Reversal with subjective neuromuscular monitoring TOFC 1 or zero = delay reversal TOFC 2 or 3 = give reversal TOFC 4 with fade = give reversal TOFC 4 with no perceived fade = give reversal, TOFC 4 and >0.9 = withhold reversal Reversal with objective neuromuscular monitoring TOFC 0 or 1 = delay reversal TOFC 2 or 3 = give reversal TOFC 4 with < 0.4 = give reversal TOFC 4 with 0.4-0.9 = give reversal TOFC 4 and >0.9 = withhold reversal Reversal guidelines with clinical neuromuscular monitoring Only consider reversal when spontaneous muscle activity is present Remember that clinical tests of adequate reversal are unreliable indicators of neuromuscular blockade