Neuromuscular Blockade Week 4 Flashcards
1
Q
The nervous system is divided into ______
A
the central and peripheral nervous system
2
Q
The peripheral nervous system is divided into _____
A
the somatic and autonomic nervous system
3
Q
The autonomic nervous systems is divided into ____
A
the sympathetic and parasympathetic nervous system
4
Q
Somatic nerves include _____
A
sensory and motor neurons
5
Q
Sensory neurons from skeletal muscle carry ____
A
action potentials to the spinal cord via the dorsal (back) horn
6
Q
Motor neurons to skeletal muscle originate in ____
A
the ventral (front) horn of the spinal cord
7
Q
Acetylcholine (ACh) is __
A
the stimulating neurotransmitter for all cholinergic receptors
8
Q
What are two major subtypes of cholinergic receptors?
A
muscarinic and nicotinic
9
Q
Where are muscarinic receptors found?
A
peripherally in tissues innervated by parasympathetic postganglionic neurons such as heart, smooth muscle and exocrine glands
Exception: sweat gland
10
Q
Where are nicotinic receptors found?
A
Locations:
- peripherally in the motor end-plate of skeletal muscle
- Cell bodies of post ganglionic (sympathetic and parasympathetic) autonomic nerves
- Central nervous system
- Adrenal medulla
- Neuromuscular junction
11
Q
ACh is released from _______
A
Preganglionic autonomic fibers
Postganglionic parasympathetic nerve fibers
Motor neurons
12
Q
Describe the Steps of the Release of Acetylcholine from the Nerve Terminal
A
- The motor nerve action potential arrives at and depolarizes a nerve terminal.
- Depolarization causes voltage-gated calcium channels to open.
- Calcium (Ca++) diffuses down a concentration gradient into the nerve terminal.
- Inside the nerve terminal, Ca++ causes vesicles to fuse with the nerve cell membrane and open to the exterior.
- ACh spills out into the synaptic cleft (exocytosis).
- The presynaptic nicotinic receptor responds to ACh by increasing the synthesis and release of Ach. This is a positive feedback system that prevents depletion of ACh at the neuromuscular junction
13
Q
Describe the Steps: Events at the Postsynaptic Membrane
A
- ACh combines with nicotinic receptors of the protein channel.
- When both alpha subunits of the nicotinic receptor channel are occupied by ACh, the channel snaps open, and sodium and calcium diffuse into the cell and potassium ions diffuse out to the extracellular space.
- The diffusion of these three types of ions through the channel causes the motor end-plate to depolarize.
- At a critical level of depolarization (threshold), an action potential is initiated.
- The action potential sweeps across the skeletal muscle cell and triggers contraction.
14
Q
Describe the steps: Termination of Neurotransmitter Action
A
- Acetylcholinesterase (AChE), also known as “true” cholinesterase, breaks down acetylcholine to choline and acetate.
- As ACh is metabolized, the motor end-plate repolarizes and the muscle cell becomes ready for another squirt of ACh from the nerve terminal.
- The choline is transported back into the nerve terminal where it is used to re-synthesize ACh
15
Q
What is the Clinical use of
Neuromuscular Blocking Agents?
A
Facilitate tracheal intubation
Reduce risk of vocal cord damage, difficult intubations, manage difficult airways
Improve surgical working condition
Mechanical ventilation
Immobility for surgery or ICU
Remember: no hypnosis or analgesia
16
Q
What are the characteristics of the ideal neuromuscular blocking agent?
A
Nondepolarizing Rapid onset
Rapid reliable recovery or reversal No histamine release
Does not accumulate in long cases
Not MH trigger Dose-dependent duration
No hemodynamic side-effects No placental transfer
Elimination independent of organ function
No active or toxic metabolites Cost effective
User friendly packaging and preparation
17
Q
Peripheral Class of Relaxants
A
Acts at NMJ on nicotinic ACh receptors
Depolarizing (mimics acetylcholine)
Nondepolarizing (interferes with the action of acetylcholine)
•Short, intermediate and long acting
18
Q
Central Class of Relaxants
A
Direct acting muscle relaxants, inhalation agents
Toxins that act at CNS (organophosphates, CNS and peripheral)
ACh central stimulants (Alzheimer’s drug, donepezil) inactivate acetylcholinesterase and increase acetylcholine circulation
19
Q
Structure and Solubility of all NMBA?
A
All NMBA are quaternary ammonium in structure
Water soluble in the body
20
Q
Do NMBA agents cross the blood brain barrier?
A
Do not cross the blood brain barrier – no CNS effects
21
Q
Intubating dose
A
NMBA Dose needed to relax a patient who is not relaxed in other ways for intubation
22
Q
Rapid Sequence Intubation dose
A
usually 1.5x intubating dose to achieve intubating conditions in 60 sec
23
Q
Relaxing dose
A
Dose given when succinylcholine used for intubation for surgical relaxation
24
Q
Supplemental dose
A
Small dose (about 1/5 intubating dose) given to continue muscle relaxation during case, as indicated
25
Onset of Neuromuscular Block
1. Diaphragm
2. Orbicularis oculi
3. Adductor pollicis
\*\*Order is the same for recovery (diaphargm "wakes" up first)
26
Succinylcholine is composed of \_\_\_\_\_
two acetylcholine molecules linked together; thus, succinylcholine mimics the action of acetylcholine.
27
Succinylcholine, after it is administered intravenously, \_\_\_\_
diffuses into tissues from the blood.
28
Those succinylcholine molecules that reach the motor nerve terminal of skeletal muscle \_\_\_\_\_.
combine with nicotinic receptors and cause the channels of the motor end-plate to open; the motor end-plate depolarizes, and a single contraction occurs.
29
acetylcholinesterase does not metabolize succinylcholine.... describe this further..
the succinylcholine remains attached to the receptors, and the channels stay open until the succinylcholine diffuses back into the circulation; depolarization is maintained for several minutes.
30
Action potentials cannot be initiated in the skeletal muscle cell until the cell \_\_\_\_\_\_.
(MOA of succinylcholine)
repolarizes (the sodium gates are in the inactivated state). Thus, so long as the motor end-plate does not repolarize, additional action potentials and hence contractions cannot be initiated. There is skeletal muscle paralysis. This is a depolarizing block.
31
Succinylcholine is metabolized by \_\_\_\_\_.
an **enzyme** in the plasma called **plasma cholinesterase**.
The metabolism of succinylcholine in the plasma is **rapid**. As the circulating succinylcholine is metabolized, **a gradient develops** for succinylcholine to diffuse from the skeletal muscle motor end-plate back into the plasma, and the effect of the succinylcholine is terminated.
32
Plasma cholinesterase is known by what two other names?
pseudocholinesterase and butyrocholinesterase.
33
Class, Absorption & Clinical Use of Succinylcholine
Class: Depolarizing muscle blocking agent
Absorption: IV, IM
Clinical use: Rapid sequence induction, laryngospasm, ECT
34
Dosing of Succinylcholine
**Induction dosing**: **1** – 1.5 **mg/kg**
IM induction: **4 mg/kg**
Laryngospasm: **20 - 40 mg**
35
Onset, DOA, and Redistribution of Succinylcholine
**Onset**: 30 – **60 seconds**
**DOA**: 5 – **15** minutes
**Redistribution**: Diffusion away from the neuromuscular junction into the ECF
36
Metabolism and Excretion of Succinylcholine
Metabolism: **Plasma cholinesterases.** Plasma choliesterases are **made by the liver.**
**Metabolism is prolonged in patients with plasma cholinesterase deficiency.**
Excretion: Eliminated by the kidneys
37
Succinylcholine can cause: \_\_\_
**Bradycardia** due to direct stimulation of muscarinic receptors of the SA node
**Hyperkalemia** risk: plasma K+ concentration may increase by **0.5 mEq/liter** in normal patients and **5–10 mEq/liter in burn, trauma, or head-injury patients**
**Increased Pressures** (ICP, IOP, gastric)
**Muscular**: Fasciculations/post op muscle pain (myalgias)
Rhabdomyolysis leading to hyperkalemia and cardiac arrest
**Masseter spasm** early sign of MH, MH trigger (malignant hyperthermia)
38
Why is succinylcholine riskier in pts with history of head trauma, skeletal muscle disease, TBI, burns, or spinal cord injury?
Each of those conditions is associated with **proliferation of "extrajunctional postsynaptic cholinergic nicotinic receptors**".
When nerve action potentials to skeletal muscle are interrupted, post- synaptic nicotinic receptors up-regulate and spread from the neuromuscular junction to the entire muscle fiber. As you know, potassium exits the cells when the nicotinic receptor is stimulated and the channel opens. The major concern, therefore, is **hyperkalemia** which may occur in these patients upon administration of succinylcholine.
39
How can we premedicate to prevent increased ICP with succinylcholine use?
defasciculating dose of non depolarizer
40
How could you prevent increased gastric pressure when administering succinylcholine?
defasciculating dose of non depolarizer
41
How long would increased IOP last with succinylcholine administration? What condition should we avoid giving it alltogether?
6 minutes
Do not give to pt with an open globe injury
42
Which types of patients are at highest risk for developing rhabdomyolosis after receiving succinylcholine?
have undiagnosed skeletal muscle myopathy, most frequently Duchenne muscular dystrophy.
43
It is recommended that the use of succinylcholine in children 8 and younger should be \_\_\_\_\_\_.
**reserved for emergency intubation** or instances where immediate securing of the airway is necessary (e.g., laryngospasm, difficult airway, full stomach) or for intramuscular use when a suitable vein is inaccessible.
44
Potential contraindications for use of Succinylcholine
Hyperkalemia Severe muscle trauma
Burn patients with injuries of over 35% total body surface area (TBSA), third-degree burn
Neurologic injury (e.g., paraplegia, quadriplegia)
Severe sepsis (e.g., abdominal) Malignant hyperthermia
Muscle wasting, prolonged immobilization, extensive muscle denervation
Duchenne muscular dystrophy Select muscle disorders
Should be used in children under 8 years old only in emergency situations; not for routine intubation
Genetic variants of pseudocholinesterase Allergy
45
The diagnosis of malignant hyperthermia is made with the unexplained signs of \_\_\_\_\_\_.
pyrexia (fever), or tachycardia, or cyanosis, or rigidity, or failure of the masseter muscle to relax (trismus).
46
What lab values are found in malignant hyperthermia?
acidosis
hyperkalemic
hypercalcemic
hypercapnia
hypoxia
47
Describe the patho of malignant hyperthermia
The defect in malignant hyperthermia is in the sarcoplasmic reticulum of skeletal muscle. The sarcoplasmic reticulum fails to sequester calcium, so sustained contractions with increased metabolism result.
48
What is used to treat malignant hyperthermia(MH)?
Dantrolene is used to treat malignant hyperthermia. Dantrolene acts on the sarcoplasmic reticulum to decrease the release of calcium to contractile proteins.
49
Signs and Symptoms of Malignant Hyperthermia
One of the earliest and most sensitive signs of malignant hyperthermia is an **unexplained doubling or tripling in end-expiratory CO2**
**Increased PaCO2** (possibly \> 100 mmHg) and decreased pH (possibly to less than 7.0).
**Sympathetic hyperactivity manifested by increased heart rate** is also an early sign of increased metabolism
**Trismus** (masseter muscle spasm) appears in 50% of patients who develop the disorder.
**Whole body rigidity** appears 75% of the time.
50
Which drugs or conditions increase succinylcholine’s DOA?
**Antibiotics** (neomycin, streptomycin, dihydrostreptomycin, kanamycin, gentamicin, polymyxin A, polymyxin B, colistin, lincomycin)
amide local anesthetics anticholinesterase agents
**hyperkalemia, hypermagnesemia**
lithium
calcium channel blockers
**inherited pseudocholinesterase defect** (atypical pseudocholinesterase)
51
Dibucaine test
(Tests if you have a pseudocholinesterase abnormality)
Local anesthetic that inhibits normal pseudocholinesterase by ~ 80%, but abnormal pseudocholinesterase types will be less inhibited
**normal = 80%**
**heterozygous = 50-60%**
**homozygous = 20%**
l% inhibited = Dibucaine #
52
What are the two classes of nondepolarizing NMBAs?
**Steroidal**: **Rocuronium** bromide, **Vecuronium** bromide, **Pancuronium** bromide
**Benzylisoquinoliniums**: **Atracurium** besylate, **Mivacurium** chloride, **Cisatracurium** Besylate
53
Quick facts about nondepolarizing agents?
ACh antagonist/blocker
Quarternary ammonium compounds
Steroids or benzoisoquinolines
Do not depolarize membrane
Reversible
Do not trigger MH
54
Mechanism of Action of Nondepolarizing NMBAs
1. After intravenous administration, a nondepolarizing neuromuscular blocker (NDNB) **circulates to all tissues**, including skeletal muscle.
2. D**iffuses from the vascular compartment into the synaptic cleft** of the neuromuscular junction.
3. C**ombines with the nicotinic** receptors of the channels of the motor end-plate.
4. **No direct effect on the channel**.
5. **Competitively blocks acetylcholine** from attaching to its receptors so the channel cannot open.
6. **The channel stays closed, and the postsynaptic membrane remains polarized.** **Thus, a nondepolarizing neuromuscular blockade is established**.
55
Class, Absorption & Use of Rocuronium
**Class**: Steroidal nondepolarizing muscle blocking agent
**Absorption**: IV
**Clinical use**: Standard and rapid sequence induction, maintenance of neuromuscular blockade
56
Dosing, Onset and Duration of Rocuronium
Dosing
Induction dosing: **0.6 – 1.2 mg/kg**
RSI dose: **1.2 mg/kg**
Distribution
Onset: **1 – 3 minutes**
DOA: **30 – 60 minutes**
57
Metabolism and Excretion of Rocuronium
Metabolism: Hepatic and renal
Excretion: Eliminated by the liver (20%) and kidneys (80%)
58
What can you give to reverse rocuronium?
sugammadex
\*remember that sugammadex can only be used to reverse steroidal NDBA
59
Class, Absorption & Use of Vecuronium
Class: Steroidal nondepolarizing muscle blocking agent
Absorption: IV
Clinical use: Standard induction and maintenance of neuromuscular blockade
60
Dosing, Onset and Duration of Vecuronium
Dosing: Induction dosing: **0.1 mg/kg**
Distribution
Onset: 2 – **4 minutes**
DOA: 30 – **60 minutes**
61
Metabolism and Excretion of Vecuronium
Metabolism
**Hepatic and renal**
Excretion
**Eliminated by the liver (50%) and kidneys (50%)**
62
What is unique about Vecuronium?
Stored in a powder and must be reconstituted before adminstration
63
Reversal of Vecurononium?
Sugammadex
64
Class, Absorption & Use of Cisatracurium
**Class**: Benzylisoquinolinium nondepolarizing muscle blocking agent
**Absorption**: IV
**Clinical use**: Standard induction and maintenance of neuromuscular blockade
65
Dosing, Onset and Duration of Cisatracurium
Dosing: **Induction dosing: 0.1 mg/kg**
Onset: 2 – **4 minutes**
DOA: 30 – **60 minutes**
66
Metabolism and Excretion of Cisatracurium
**Metabolism**: Hofmann elimination (75%) and nonspecific esterase hydrolysis (25%)
**Laudanosine metabolite**, which is a CNS stimulant
•20% less laudanosine is produced when compared to atracurium
Excretion
lEliminated by the kidneys
67
What is Hofmann elimination?
a temperature- and pH-dependent break- down of the drug molecule.
68
Class, Absorption & Use of Atracurium
Class: Benzylisoquinolones nondepolarizing muscle blocking agent
Absorption: IV
Clinical use: Standard induction and maintenance of neuromuscular blockade
69
Dosing, Onset and Duration of Atracurium
Dosing: **Induction dosing: 0.5 mg/kg**
Onset: 2 – **4 minutes**
DOA: 30 – **60 minutes**
70
Metabolism and Excretion of Atracurium
Metabolism
Hofmann elimination and nonspecific esterase hydrolysis
**Laudanosine metabolite**, which is a CNS stimulant
Excretion
Eliminated by the kidneys
71
Atracurium & Mivacurium can \_\_\_.
release histamine and cause hypotension, tachycardia, and flushing
72
Pancuronium is \_\_\_\_\_.
**vagolytic** and causes slight catecholamine release (indirect sympathomimetic), producing tachycardia.
73
rocuronium, vecuronium, and pancuronium have what in common regarding elimination?
all depend on both renal and hepatic elimination
(in varying degrees)
74
What two drugs are the most common in intraoperative allergic reactions?
Neuromuscular blocking agents and antibiotics
75
How is an allergy to NMBA determined?
The initial diagnosis is presumptive, whereas the etiological assessment is linked to the clinical presentation, tryptase levels, and skin test results
76
Anaphylaxis to NMBAs present with \_\_\_.
significant hypovolemia and vasoplegia
77
How is anaphylaxis to NMBAs managed?
Aggressive fluid therapy and epinephrine
78
Which patient exhibits a prolonged duration of action to all muscle relaxants?
Hypothermic patients
10-15% ↓ for every degree below 36 ▪ Most with cis and atrac due to Hofmann (**colder = slower**)
79
Which drugs can prolong the effect of Nondepolarizing NMBAs?
Volatiles (desflurane the most often)
Magnesium
Lithium
IV local anesthetic ▪ If on drip, check dosing!
80
Which conditions/drugs can shorten the effect of Nondepolarizing NMBAs?
Long term anti-epileptics – resistant to NMB
Steroids antagonize NMB
81
Describe the pathway of a NMBA through the body
Inject into intravascular system: High Plasma Concentration of ionized drug
Tissue concentration increases
Effect is seen, drug bound to receptor
Elimination starts and plasma concentration decreases
Drug leaves tissues and enters plasma
Diminished effect
Eliminated or metabolized
82
How do we assess for NMBA reversal? (3 main categories)
**Peripheral Nerve Stimulator**: Qualitative Train of Four (TOF) inexact science
Single twitch (appropriate for depolarizing block)
Train of four Double burst Sustained tetanus
**Respiratory mechanics**: Vital Capacity 15-20 cc/kg & Inspiratory force -40 cm H2O
**Physical Performance**: Hand grip, Opens eyes, Sustained head lift (5-10 seconds), Strong cough
83
Describe how a single twitch assesses NMBA blockade
**a single pulse that is delivered at 70 - 80 mA for 0.1msec.** Increasing block results in decreased evoked response to stimulation.
Train of four (TOF) denotes a frequency of 2 Hz (four (4) successive stimuli every 0.5 seconds).
The twitches in the TOF pattern progressively fade as relaxation occurs. It is more convenient to visually observe the sequential disappearance of the twitches. Used with NDMR, you also see fade.
\*disappearance of the 4th twitch = 75% blockade
\*disappearance of the 3rd twitch = 80% blockade
\*disappearance of the 2nd twitch = 90% blockade
84
Clinical relaxation requires what percentage of blockade via TOF?
75-95% neuromuscular blockade
85
Qualitative vs. Quantitative TOF
**Qualitative TOF**: Visual and tactile response of electrical stimulus assessed by clinician
**Quantitative**: Stimulator coupled with displacement transducer to measure movement, a value number is displayed
86
Characteristics of a Phase I Block
**Fasciculations appear prior to paralysis.**
Block is enhanced (augmented) by cholinesterase inhibitors (edrophonium, neostigmine, pyridostigmine).
Amplitude of single twitch contractions decreases in proportion to the severity of the block.
**Fade does not occur during tetanic stimulation** or train-of-four stimulation, although the amplitudes of the tetanic contraction and train-of-four beats are reduced.
The train-of-four ratio (amplitude of fourth beat to amplitude of first beat) is greater than 70% (T4/T1 \>70% = T4/T1 \>0.7).
Post-tetanic facilitation (post-tetanic potentiation) is absent.
**Block is antagonized by nondepolarizing muscle relaxants**.
87
Transition from Phase I to Phase II Block
In phase I block, **the motor end-plate is depolarized**; succinylcholine has activated the nicotinic receptors of the motor end-plate and the ion channels have opened and remained open.
Treatment **with higher doses of succinylcholine and/or prolonged exposure of the motor end-plate to succinylcholine leads to the development of phase II, or desensitization, block**.
Phase II (desensitization) block is a very complex phenomenon; **ion channels of the motor end-plate close for reasons that are unknown**, and the **motor end-plate repolarizes**.
Phase II block has the characteristics of a nondepolarizing block; use of a peripheral nerve stimulator during phase II block will show fade and post-tetanic facilitation.
88
Characteristics of a Phase II Block
**Muscle fasciculations do not appear prior to paralysis.**
Block is antagonized by agents that inhibit true acetylcholinesterase (edrophonium, neostigmine, pyridostigmine).
Amplitude of single twitch contractions decreases with increasing intensity of block.
Fade occurs during train-of-four stimulation and also during tetanic stimulation.
Post-tetanic facilitation (potentiation) is present.
The train-of-four ratio (amplitude of fourth beat to amplitude of first beat) is less than 70%.
(T4/T1 \< 70%).
89
Best area to measure onset of blockade (intubating conditions) = \_\_\_\_
Muscle = orbicularis oculi (close eyelid) or corrugator supercilia (eyebrow twitch)
Nerve = Facial
90
Best place to measure recovery of blockade (return of airway muscle function) = \_\_\_\_\_.
Muscle = adductor pollicis (thumb adduction) or flexor hallucis (big toe flexion)
Nerve = ulnar nerve or posterior tibial nerve
91
General Assessment of NMBA reversal
Evidence of return of NM function
Patient temperature
Extent of surgery
Fluids
What NM blockers were used, last dose,
Acid –base –electrolyte derangements
Renal/hepatic function
Other drugs
92
Questions to ask yourself when selecting a drug
Patient information/comorbidities
What is needed to accomplish airway management?
Is difficult ventilation or intubation anticipated?
Does the patient have a full stomach?
What is needed to complete the surgery?
Can the patient breath spontaneously?
How brief may the surgery be?
Cost effectiveness?
93
Why is the adductor pollicis the gold standard to monitor NMB?
it is the only hand muscle **solely innervated by the ulnar nerve** so it is less likely that you would be getting false twitches from direct muscle stimulation rather than nerve stimulation
"There is more than meets the eye; a hand is needed."
94
What are we looking for in terms of vital capacity to assess recovery of NMBA?
VC greater than or equal to 20mL/kg
This would mean that a maximum of 70% of receptors are occupied when this clinical enpoint is acheived
95
Acceptable clinical endpoint for tidal volume when assessing recovery of NMBA?
greater than or equal to 5mL/kg
This would mean that a maximum of 80% of receptors are occupied when this clinical enpoint is acheived
96
What would be an acceptable clinical enpoint for the TOF to assess readiness to extubate?
no fade
This would mean that a maximum of 70% of receptors are occupied when this clinical enpoint is acheived
97
What would be an acceptable clinical endpoint for insiratory force when assessing readiness to extubate?
Inspiratory force better than -40cm H20
This would mean that a maximum of 50% of receptors are occupied when this clinical enpoint is acheived
