Introduction to Critical Care and Sustained Neuromuscular Blockade

Question 1

Neuromuscular blocking agents (NMBAs, paralytics)

Answer 1

specific application in critical care
two types: depolarizing, nondepolarizing

Question 2

Depolaring agent

Answer 2

succinylcholine

Question 3

Succinylcholine

Answer 3

physically resembles Ach: binds and activates Ach receptors; sustained depolarization of neuromuscular junction –> muscle contraction can’t occur; hydrolyzed much more slowly than Ach
may cause initial muscle contractions; rapid onset and duration
elimination –> rapidly hydrolyzed in serum by the enzyme psuedocholinesterase

Question 4

Succinylcholine used for

Answer 4

rapid sequence intubation (RSI): placement of an endotracheal tube; permits complete airway control and simplifies visualization of vocal cords - can cause initial muscle contractions, may pre-administer defasciculating dose of nondepolarizing NMBA immediately prior to succinylcholine
NOT used for sustained neuromuscular blockade

Question 5

Succinylcholine: ADRs

Answer 5

APNEA –> need to be ready to intubate (causes paralysis of respiratory muscles)
muscle fasciculations –> deep aching muscle pain, may persist for days
hyperkalemia –> precise mechanism unknown: asynchronous depolarization of muscle cells, alterations in receptor sensitivity, contraindicated in major burns, crush injury, and upper motor neuron disease - potential life threatening hyperkalemia, unclear the precise duration that these contraindications should persist
prolonged apnea: result of impaired pseudocholinesterase activity or decreased pseudocholinesterase levels
intracranial pressure (ICP) elevation (controversial in traumatic brain injury)
increased intraocular pressure

Question 6

Nondepolarizing NMBAs MOA

Answer 6

competitively block the action of Ach (do NOT activate receptors): do not cause initial fasciculations, competitive (binds Ach receptor, prevents Ach from binding)

Question 7

Nondepolarizaing NMBAs - 2 general classes

Answer 7

aminosteroidal
benzylisoquinolinium

Question 8

Reversal of nondepolarizaing NMBAs

Answer 8

possible, but not generally used in the ICU
acetylcholinesterase inhibitors (pyridostigmine, neostigmine)
sugammadex: modified A-cyclodextrin for reversal of rocuonium/vecuronium; not extensively evaluated in ICU

Question 9

Nondepolarizing NMBAs - clinical indications

Answer 9

may be used for both immediate/sustained paralysis: selected agent based on pt factors/drug pharmacology
mechanical ventilation
operative settings
RSI
manage increased ICP
therapeutic hypothermia
decreased oxygen consumption

Question 10

NDNMBAs - mechanical ventilation

Answer 10

generally in pts with acute lung injury or acute respiratory distress syndrome (ARDS) - 25-50% of ARDS pts, recommended to administer as a continuous infusion
prevents dysynchrony with ventilator, stops spontaneous respiratory effort
improves gas exchange
facilitates “nontraditional” methods of ventilation
NOT required in all mechanically ventilated pts (not everyone on vent requires a sustained paralytic, often just used if pt has ARDS)

Question 11

NDNMBAs - operative settings

Answer 11

muscle relaxation

Question 12

NDNMBAs - RSI

Answer 12

if contraindications to succinylcholine (burns, etc)
fast acting agent + short duration (rocuronium)

Question 13

NDNMBAs - manage increased ICP

Answer 13

problem: as you increase ICP –> tissue damage + decrease in perfusion; if you paralyze someone with neurotrauma –> pt can’t talk, blink, respond to anything, can’t do neuro function tests
typically reserve for pts with severe posturing, difficulties in mechanical ventilation, refractory increase ICP

Question 14

NDNMBAs - therapeutic hypothermia

Answer 14

body temperature 32-34 degrees celsius post cardiac arrest
NDNMBAs used to prevent/treat shivering
decrease metabolism, decrease formation of free radicals/toxic metabolites

Question 15

NDNMBAs - decrease oxygen consumption

Answer 15

controversial –> severe sepsis may be associated with high oxygen demands, may improve supply-demand relationship

Question 16

NDNMBAs ADRs - paralysis of respiratory muscles/apnea

Answer 16

safeguards to prevent unplanned extubation
safeguards to prevent errors
ex narcan vs norcuron, storage + labeling –> to prevent name mixups

Question 17

NDNMBAs ADRs - inadequate pain and sedation

Answer 17

NMBAs do not provide analgesic, sedative, or anxiolytic effect (only provide paralytic effect)
pts still feel pain and anxiety, however are unable to communicate
assessment of pain and sedation is very difficult (i.e. no longer able to assess typical sx of pain and anxiety)
pts must be optimized on sedative and analgesic drugs!! (ideally prior to initiation of NMBA

Question 18

NDNMBAs ADRs - prolonged paralysis/muscle weakness

Answer 18

ICU-acquired skeletal muscle weakness (ICUAW), also called - acute quadriplegic myopathy syndrome, critical illness myopathy, or critical illness polyneuropathy
multifactorial: pharmacokinetic effects (accumulation) possible pharmacodynamic effects; risk increased with prolonged NMBA administration, possibly increased with corticosteroids, sepsis/septic shock; drug holidays (periodically stopping paralytic) may decrease the incidence of AQMS

Question 19

NDNMBAs ADRs - misc ADRs

Answer 19

related to immobility: DVT prophylaxis, ocular lubricants (to prevent corneal ablasion)
drug interactions: corticosteroids and NMBAs - cause prolonged muscle weakness

Question 20

Monitoring sustained NMB

Answer 20

challenging
associated with significant variability in response
goal: lowest dose possibe, minimization of ADRs - efficacy endpoint –> based on clinical indication, difficult to assess (a lot of people use toxicity endpoint as efficacy endpoint)

Question 21

Toxicity endpoint

Answer 21

toxicity endpoint –> peripheral nerve stimulation (twitch monitoring, train of 4 assessment)

Question 22

Train of four assessment

Answer 22

nerve (ulnar nerve or temporal branch of facial nerve) stimulated 4 times
number of muscle twitches recorded: 4/4 –> <75% suppression; 3/4 –> 75% suppression; 2/4 –> 80% suppression; 1/4 –> 90% suppression; 0/4 –> 100% suppression
usually adjust dose to 1-2 twitchs of train: titrating to 0/4 generally should be avoided