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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Chapter 18 Skeletal Muscle Relaxants (Neuromuscular Blocking Agents)

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Presentation on theme: "Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Chapter 18 Skeletal Muscle Relaxants (Neuromuscular Blocking Agents)"— Presentation transcript:

1 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Chapter 18 Skeletal Muscle Relaxants (Neuromuscular Blocking Agents)

2 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Uses of Neuromuscular Blocking Agents  Facilitate intubation  Surgery  Enhance ventilator synchrony  Reduce intracranial pressure (ICP)  Reduce O 2 consumption  Terminate status epilepticus and tetanus  Facilitate procedures and studies  Keep patients immobile

3 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Physiology of the Neuromuscular Junction  CNS  Brain  Spinal cord  PNS  Somatic motor nervous system (skeletal) Voluntary control Voluntary control  Autonomic nervous system Involuntary control Involuntary control

4 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Physiology of the Neuromuscular Junction (cont’d)  Neuron  Cell body  Axons  Dendrites  Neurotransmitter  Acetylcholine  Acetylcholinesterase (AChE)

5 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Physiology of the Neuromuscular Junction (cont’d)  Depolarization  Action potential occurs  Repolarization  Membrane potential returns to baseline

6 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Physiology of the Neuromuscular Junction (cont’d)  Two ways to block muscle contraction  Competitive inhibition Nondepolarizing agents Nondepolarizing agents  Prolonged occupation and persistent binding Depolarizing agents Depolarizing agents

7 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nondepolarizing Agents  Block acetylcholine receptors without activating them  Mode of action  Affect postsynaptic cholinergic receptors  Compete against endogenous acetylcholine  Effect is dose related  Acetylcholinesterase inhibitors (neostigmine) can reverse blockade

8 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nondepolarizing Agents (cont’d)  Pharmacokinetics of nondepolarizing agents  Chemically resemble acetylcholine  Onset of paralysis and duration of action vary widely and are dose dependent  Duration can be increased by Advanced age Advanced age Hepatic or renal failure Hepatic or renal failure

9 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nondepolarizing Agents (cont’d)  Metabolism  When normal conduction returns, 75% of receptors may still be occupied by blocker Additional boluses may appear more potent Additional boluses may appear more potent  d-Tubocurarine and doxacurium Minimally metabolized Minimally metabolized  Pancuronium Hepatic metabolism Hepatic metabolism

10 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nondepolarizing Agents (cont’d)  Metabolism (cont’d)  Atracurium and cisatracurium Spontaneous degradation by pH and temperature Spontaneous degradation by pH and temperature  Vecuronium Hepatic metabolism Hepatic metabolism  Mivacurium Shortest acting (10 to 20 minutes) Shortest acting (10 to 20 minutes) Eliminated by plasma cholinesterase Eliminated by plasma cholinesterase

11 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nondepolarizing Agents (cont’d)  Adverse effects and hazards  Cardiovascular effects Vagolytic effect Vagolytic effect  Histamine release Cause histamine release from mast cells Cause histamine release from mast cells  Inadequate ventilation Paralysis of diaphragm and intercostals Paralysis of diaphragm and intercostals

12 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nondepolarizing Agents (cont’d)  Reversal of nondepolarizing blockade  Produced by cholinesterase inhibitors  Inhibits cholinesterase that breaks down acetylcholine  Allows more acetylcholine at junction to displace blocker  Agents Neostigmine Neostigmine Edrophonium Edrophonium Pyridostigmine Pyridostigmine

13 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Depolarizing Agents  Mode of action  Depolarizes muscle membrane like acetylcholine Resistant to AchE for longer period Resistant to AchE for longer period Causes fasciculations Causes fasciculations  Phase I block Prolonged depolarization/flaccid paralysis Prolonged depolarization/flaccid paralysis  Phase II block Resembles nondepolarizing block Resembles nondepolarizing block Limits use in repeat doses Limits use in repeat doses

14 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Depolarizing Agents (cont’d)  Metabolism  Rapid hydrolysis by plasma cholinesterase  Reversal  No agents available for reversal of succinylcholine

15 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Depolarizing Agents (cont’d)  Adverse effects and hazards  Sympathomimetic response  Vagal response with repeat boluses  Muscle pain/soreness  Hyperkalemia  Increased intracranial, intraoptic, and intragastric pressure  Malignant hyperthermia

16 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Neuromuscular Blocking Agents and Mechanical Ventilation  Used to improve ventilation and oxygenation and to reduce pressure  Beneficial in:  Status asthmaticus  Inverse ratio ventilation and high-frequency oscillatory ventilation (HFOV)  Status epilepticus  Neuromuscular toxins  Tetanus  Acute respiratory distress syndrome (ARDS)

17 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Neuromuscular Blocking Agents and Mechanical Ventilation (cont’d)  Precautions and risks  Proper eye care  Suctioning  Proper sedation and analgesia  Aspiration/nosocomial pneumonia  Risk of prolonged skeletal muscle weakness  Decubitus ulcers  Deep venous thrombosis (DVT)

18 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Neuromuscular Blocking Agents and Mechanical Ventilation (cont’d)  Use of sedation and analgesia  Absolutely essential!  Monitor for tachycardia, hypertension, diaphoresis, and lacrimation  Analgesics Fentanyl Fentanyl Morphine Morphine  Amnestic sedatives Propofol Propofol Lorazepam Lorazepam Midazolam Midazolam

19 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Neuromuscular Blocking Agents and Mechanical Ventilation (cont’d)  Interactions with neuromuscular blocking agents  Inhaled anesthetics potentiate blockade  Aminoglycosides also produce NMB  Agents antagonizing NMB Phenytoin Phenytoin Azathioprine Azathioprine Theophylline Theophylline  Potentiate blockade Acidosis Acidosis Hypokalemia Hypokalemia Hyponatremia Hyponatremia Hypocalcemia Hypocalcemia Hypomagnesemia Hypomagnesemia

20 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Neuromuscular Blocking Agents and Mechanical Ventilation (cont’d)  Choice of agents  Situation dependent  Factors Duration of procedure Duration of procedure Need for quick intubation Need for quick intubation Adverse effects Adverse effects Route of elimination Route of elimination Drug interactions Drug interactions Cost Cost

21 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Monitoring of Neuromuscular Blockade  Paralysis may mask clinical signs/symptoms  Methods  Visual  Tactile  Electronic

22 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Monitoring of Neuromuscular Blockade (cont’d)  Loss of muscle activity  Eyelids  Face  Neck  Extremities  Abdomen  Intercostals  Diaphragm  Return of muscle activity  Occurs in reverse order

23 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Monitoring of Neuromuscular Blockade (cont’d)  Twitch monitoring  Train-of-four evaluation  2 Hz over 2 seconds 0 twitches = 100% blockade 0 twitches = 100% blockade 1 twitch = 95% blockade 1 twitch = 95% blockade 2 twitches = 90% blockade 2 twitches = 90% blockade 3 twitches = 80% blockade 3 twitches = 80% blockade 4 twitches = <75% blockade 4 twitches = <75% blockade

24 Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. The Future of Neuromuscular Blocking Agents and Reversal  Gantacurium  Nondepolarizing  Rapid onset  Short-acting  Organ-independent inactivation  Less histamine release  Sugammadex  Inactivates and removes NMBA  Reverses rocuronium and vecuronium  Less effective on pancuronium, succinylcholine, and benzylisoquinoliniums


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