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Anesthesia Pharmacology > Lecture 15 (Exam 4) - NMBD Reversal Agents > Flashcards

Lecture 15 (Exam 4) - NMBD Reversal Agents Flashcards

1
Q

Castillo talked about this case study where everything went wrong and the patient died.

Flip card to learn how to NOT fuck around find out. 😮‍💨

A

These are the factors that were identified that led to the patient’s death.

*They pulled out the ETT without fully reversing the patient.
* Intubation skills were not on fleek.
* The team did not communicate with one another.

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2
Q

What are sugammadex’s side-effects?

A

Dose related: nausea/vomitting, pruritis, urticaria
Anaphylaxis
Marked bradycardia
Doesn’t work ??
(same type of reaction with protamine. Give full dose of suggamadex but slowly.)

Slide 32

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3
Q

Why do we use monitoring with reversal agents?

A

Our assessment alone (quantitative) does not suffice as you can see by the 44% of residual block therefore we will use monitoring to assess any residual block to ⬆ safety :)

Slide 4

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4
Q

When is the best time to get a baseline TOF?

A

Immediately before giving your intubating dose of NMBA. (post lido, opioids and propofol –> like we do in SIM 😁)

Slide 7

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5
Q

List the 5 NMBA reversal drugs.

List the 2 Anti-Cholinergic Agents we use.

Why do we give these in conjunction?

What is the one NMBA Reversal that does not require a conjunction med?

A

We give an anti-cholinergic to blunt the S/E of the reversal agent. (bradycardia, n/v, pruritic, urticaria, etc.)

Sugammadex

Slide 8

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6
Q

List some cautions for sugammadex.

A
  • Oral contraceptives (Binds w/ progesterone for 7 days. Make sure you tell your patients to use other forms of birth control!)
  • Toremifene (non-steroidal anti-estrogen) –> displaced by suggamadex (for pt’s with hx of breast cancer)
  • Coagulopathy/Bleeding –> Heparin/LMWH, elevated PTT, PT, INR
  • Recurarizaiton –> does not happen w/ appropriate dosage unless lower than recommended dosage given.
    (Less than recommended dosage of suggamadex is not enough to reverse the paralytic agent, hence pt will continue to have NMB)

Slide 34

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7
Q

What is NMB reversal agents MOA?

A

They are Acetylcholinesterase (AChE) inhibitors that allow boss-ass ACh to flourish thus allowing it to compete with our previously given NMB on the nACh-r.

Also called Cholinergic Agents or Competitive Antagonists (technically this should be Indirect Competitive Antagonists…but w/e)

Slide 9

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8
Q

You have already given sugammadex as your NMB reversal to your patient after the surgeon has already closed up the belly. While the surgery tech is counting the sponge, he finds out that one sponge is missing. He looks for it everywhere, even in the trash can. He did not find it. Now, the surgeon thinks that the sponge might have been left in the abdomen and need to open up the belly again. How long do you have to wait before you give another dose of rocuronium and how much dosage do you need to give?

A

5 minutes and administer a dose of 1.2 mg/Kg rocuronium
Slide 33

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9
Q

In previous patient, you gave neostigmine instead of sugammadex in the same situation. Now how long do you need to wait before you give another dose of roc and vec. What are the dosages of rocuronium and vecuronium would you give?

A

4 hours wait time after reversal with neostigmine for another dose of NMB
Give 0.6mg/kg rocuronium or 0.1 mg/kg vecuronium
Slide 33

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10
Q

Same patient in the previous slide, where you gave neostigmine as a reversal; you cannot wait 4 hours to reestablish the blockade with aminosteroid NMB. What NMB can you give to this patient?

A

Benzylisoquinolinium (Cisatricurim, mivacurium and atricurium)
Slide 33
(Sugammadex is ineffective against Benzylisoquinolinium and succinylcholine)

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10
Q

Where is our desired site of action for NMB reversal agents?

What is the reason we may see side effects?

A

The NMJ.

We may see side effects because we give these meds IV –> systemic distribution (along with NMJ & Muscarinic receptors)

Slide 10

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11
Q

What does AChE do again? & how does it do it? (enzyme reaction)

What subunit(s) on the nACh-r does ACh bind to?

A

Eats that ACh azz up by rapid hydrolysis (catalyze)

ACh binds to the alpha subunits (2)

Slide 10

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12
Q

Your patient has 0/4 twitches. What will you do?

A. Give MAX doses of all the reversals
B. Give 50 mcg/kg Neostigmine
C. Give 1 mg/kg Edrophonium
D. Go to lunch since they aren’t gonna move
E. Just wait…

A

E. Just wait you impatient swine.
- if you give a reversal this can prolong the blockade bc of the CEILING EFFECT

DO NOT give reversals when your patient is in a DEEP block!

Slide 11

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13
Q

Persistent NM blockade occurs when what two things occur?

A

Acetylcholinesterase is maximally inhibited and no further anti cholinesterase is effective
Slide 21

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14
Q

What can you do as an anesthesia provider if your patient experiences persistent NM blockade/recurarization?

A

Sedation and post-op ventilation
Slide 21

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15
Q

What are three patient conditions that influence NMBD reversal?

A

Metabolic Acidosis
Respiratory Acidosis
Hypothermia
Slide 22

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16
Q

What are the five factors influencing NMBD reversal?

A
  1. Intensity of block
  2. The NMBD used
  3. Continued volatile anesthetics
  4. The reversal agent used
  5. Patient conditions (Hypothermia, acidosis)
    Slide 22
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17
Q

Purified human plasma cholinesterase has worked with reversing which NMB drug previously?

A

Mivacurium
Slide 23

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18
Q

In the past, Cysteine has worked well with what drug for NMBD reversal?

A

Gantacurium
Slide 23

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19
Q

Sugammadex selectively binds with drugs that have which chemical compound?

A

Aminosteroid
Slide 23

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20
Q

Sugammadex is renally excreted due to its high _________ solubility.

A

Water
Slide 25

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21
Q

What is the chemical make-up of Sugammadex?

A

γ-cyclodextrin
Slide 25

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22
Q

True or False: The main mechanism of action of Sugammadex is in the NMJ.

A

False.
The main MOA is through encapsulating “free drug” in the PLASMA.
Slide 26

23
Q

Sugammadex can be used to reverse which drugs?

A

Rocuronium > Vecuronium > > Pancuronium
Slide 26

24
Q

The reversal that accompanies Sugammadex administration is caused by…

A

Encapsulation of the free drug in circulation
Slide 26

25
Q

Pharmacokinetics for excretion/clearance of NMBD reversal agents:

Where and what % do they get excreted and cleared?
-Neostigmine
-Pyridostigmine
-Edrophonium

A

Neostigmine: 50% Renal excretion
Pyridostigmine and Edrophonium: 75% Renal excretion

AND/OR: 30-50% Hepatic clearance (if no renal function)

(slide 17)

26
Q

For Neostigmine, Pyridostigmine, and Edrophonium: what can cause a decrease in plasma clearance?
- what can this cause?

A

Chronic renal disease
- Causes prolonged action

(slide 17)

27
Q

What are some unintended s/e of our NMBD reversal agents?
1. CV
2. Pulmonary
3. GI
4. Eyes

A
  1. CV: Bradycardia, dysrhythmias, asystole, ↓SVR
  2. Pulmonary: Bronchoconstriction, increased airway resistance, increased salivation
  3. GI: Hyperperistalsis, enhanced gastric fluid secretion, PONV
  4. Eyes: Miosis

“SLUDGE-M”

(slide 18)

28
Q

Why do we get these unintended s/e of our NMBD reversal agents?

A

Bc they Increased Nicotinic/Muscarinic Activity
(not only at the neuromuscular junctions (NMJ) but also at post-ganglionic SNS/ PNS

(slide 18)

29
Q

What can we do to counteract these unintended s/e of our NMBD reversal agents?

A

Giving anticholinergic/antimuscarinic agents: Atropine sulfate/ glycopyrrolate
(give it 1:1)

(slide 18)

30
Q

The 2 drugs do we use to counteract these unintended s/e of our NMBD reversal agents?

When would we only give 1/2 of the dose instead of the normal 1:1 ratio?

A

Atropine sulfate & glycopyrrolate

In instances when the pt has inherent tachycardia - full dose would increase HR more! - so give 1: 0.5 ratio ❤️❤️❤️

(slide 18)

31
Q

The Anti-Cholinergic Agent, Atropine:

Why do we give this with our NMBD reversal agents?
What’s the Dose:
And what NMD drug profile does it match with?

A

To counteract SNS/PNS effects - (Atropine can cause mydriasis and tachycardia)
Dose: 7 to 10 µg/kg (0.007 to 0.010 mg/kg)
Edrophonium

(slide 19)

32
Q

With our Anti-Muscarinic Agent, Glycopyrrolate:

Why do we give this with our NMBD reversal agents?
What the Dose:
And what drug profile does it match with?

A

To counteract SNS/PNS effects
7 to 15 µg/kg (1 mg maximum)
Neostigmine and Pyridostigmine

(slide 19)

33
Q

What is a “clinical pearl” with heart disease for which Anti-Cholinergic/ Anti-Muscarinic Agent you would prefer to use? And why?

A

Glycopyrrolate preferred (bc it has a slower onset)
Admin slowly- over 2-5 min to prevent adverse CV effects - increasing HR

(slide 19)

34
Q
A

Using 10mcg/kg:
Answer:
- 100kg x 10mcg = 1000mcg
- 1mg = 1000mcg
- 1000mcg = 1mg
= 5ml

(slide 20)

35
Q

What are the 5 factors that contribute to NM blockade reversal?

A
  1. Depth of NM block.
  2. AChe inhibitor of choice.
  3. Dose administered.
  4. Rate of plasma clearance of NMBD.
  5. Anesthesia agent choice and depth.
    (Slide 12)
36
Q

Dr. Castillo mentioned these brief highlights about Pancuronium, Vecuronium, and Mivacurium.

A

Pancuronium - only long acting NMBD in use. Will increase HR/MAP/CO (blocks vagal effect on SA node), which may be useful in some cardiac cases.

Vecuronium - only NMBD that needs reconstituted with distilled water or sterile water.

Mivacurium - only short acting NMBD, however no longer in use in the US.

(Slide 13)

37
Q

If you’re reversing a NMBD with Neostigmine, you should also give this drug.

A

Give 0.2 mg of glycopyrrolate/robinol for every 1 ml of Neostigmine that you give.

Neostigmine will block AChe so there is an increase in ACh, but this effect will occur in nACh - R and Muscarinic ACh - R. Activation of mACh - R —> bradycardia, bronchoconstriction, increased saliva. We don’t want that when waking up, so we give Glycopyrrolate to block ACh at mACh - R.

(Slide 14, Stoetling Pharm)

38
Q

Neostigmine dosing for NMBD reversal.

A

40 - 70 mcg/kg
Onset 5 - 10 min
Duration 60 min

Give with glycopyrrolate 0.2mg/ml of Neostigmine

(Slide 14)

39
Q

Sugammadex dosing.

A

2 - 16 mg/kg
Onset 1 - 4 min
Duration 1.5 - 3 hrs

Do not need to give an anticholinergic with this.
(Slide 14)

40
Q

Edrophonium dosing

A

1mg/kg
Onset 1 - 2 min
Duration 5 - 15 min

Edrophonium is an AChe - I, while not outright stated in lecture, you could infer that you might need to give atropine or glycopyrrolate to block mACh - R as you would with neostigmine. Edrophonium is very short acting, so you might not need to give an anticholinergic.

(Slide 15)

41
Q

A 41 yo 100 kg female pt had surgery and we are now closing. TOF = 2/4. Neostigmine is available at 1mg/ml. How much neostigmine do you give, if you decide to dose at 50 mcg/kg of neostigmine?

A

100 kg x 50mcg/kg = 5000 mcg

5000mcg/1000 mcg = 5 mg

Therefore, you will need to give 5 ml of neostigmine.

(Slide 16)

42
Q

What type of patient is Sugammadex contraindicated? (elimination)

A

Patients on dialysis
Dialysis cannot clear Sugammadex from the blood.

(Slide 27)

43
Q

What is the major route of elimination for Sugammadex?

How much is eliminated in 6 hours?
How much is eliminated in 24 hours?

A

Eliminated via urine

70% in 6 hours

90% in 24 hours

(Slide 27)

44
Q

Do we need to give glycopyrrolate or atropine with sugammadex?

A

No

(Out of Castillo’s face hole)

45
Q

How much Suggamadex do we give a patient presenting with 2 out of 4 twitches with T04 stimulation?

A

2mg/kg for a moderate block

(Slide 28)

46
Q

How much Suggamadex do we give a patient presenting with 1-2 post-tetanic counts but has no twitch responses to T04 stimulation?

A

4mg/kg for a deep block

(Slide 28)

47
Q

How much Suggamadex do we give a patient presenting with no T04 twitches and no post-tetanic twitches?

A

8-16 mg/kg for extreme block

Castillo says most practitioners he knows just go ahead and give 16mg/kg

(Slide 29)

48
Q

Check out this cool chart comparing recovery times with use of Suggamadex vs. Neostigmine with reversal of Rocuronium.

A

Slide 30

49
Q

Check out another cool chart comparing recovery times with use of Suggamadex vs. Neostigmine with reversal of Vecuronium.

A

Slide 31

50
Q

You get a call from PACU that the pt you recently transferred there is now experiencing declining SaO2 readings and has ⬇️ respiratory effort. What might this be labeled as?

A

Recurarization

(slide 37)

51
Q

What are other s/s of recurarization?

_________ O2 sats
____________ patient
appears “______” or uncoordinated
ineffective abdominal and ___________ activity

A

⬇️ O2 sats
unresponsive patient
appears “floppy” and uncoordinated
ineffective abdominal and intercostal activity

(slide 37)

52
Q

For each NMBD Reversal agent, give the appropriate range of doses, onset of action, and duration of action.

Edrophonium

Neostigmine

A

Edrophonium:
- Dose = 0.5-1.0 mg/kg
- OOA = 1-2 mins
- DOA = 5-15 mins

Neostigmine:
- Dose = 40-70 mcg/kg
- OOA = 5-10 min
- DOA = 60 min

(slide 38)

53
Q

More on Recurarization s/s:

T/F: Sometimes the affected pt can verbalize.
If they do verbalize, what do they complain of most often?

T/F: Affected pt is able to sustain head lift or hand grasp.

What is the worst case scenario with this affliction?

A

True
Often c/o “suffocating feeling”

False: Affected pts are unable to sustain head lift or hand grasp

Worst-case scenario: pharyngeal collapse and respiratory obstruction

(slide 40)

54
Q

Treatment goals for Recurarization:

Re-_______ the pt

Give __________ reversal agents in _______ doses

What’s an example dose?

A

Re-sedate the pt

Give ADDITIONAL reversal agents in DIVIDED doses

Ex. Neostigmine 0.05 mg/kg IV = longer DOA

(slide 40)

55
Q

What are the clinical duration of response times (in mins) of the following that were given in slide 39, Table 12-2?

Long-acting
- d-Tubocurarine
- Pancuronium

Short-acting:
- Mivacurium

A

Long-acting:
- d-Tubocurarine = 81
- Pancuronium = 86

Short-acting:
- Mivacurium = 16.8

(slide 39, Table 12-2)

56
Q

What are the clinical duration of response times (in mins) of the following that were given in slide 39, Table 12-2?

Intermediate-acting:
- Rocuronium
- Vecuronium
- Cisatracurium
- Atracurium

A

Intermediate-acting:
- Rocuronium = 36
- Vecuronium = 44
- Cisatracurium = 45
- Atracurium = 46

(slide 39, Table 12-2)

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