Issues in the critically Ill

Question 1

List the indications for sedation

Answer 1

Maintenance: Treatment of anxiety and agitation, aid mechanical ventilation, control intracranial pressure, ablate muscle spasms associated with tetanus, prevent shivering, decrease oxygen consumption

Question 2

What is the difference between mechanical ventilation and intubation?

Answer 2

Mechanical ventilation is used for patients with respiratory failure or inability to protect their own airways to help them oxygenate. Before mechanical ventilation can occur they patient must be intubated (tube placed into trachea that goes into lungs)

Question 3

What is the relationship between sedation and analgesia?

Answer 3

Any patient who is going to be sedated should have analgesic medications on board.

Question 4

What is a daily sedation vacation?

Answer 4

Sedative and analgesic medications are d/c each morning. If the patient is able to follow simple commands and is calm, the medications can be held. If patient is agitated, restart sedative infusion at half the original rate and titrate throughout the day PRN.

Question 5

What outcomes are reduced during sedation vacation

Answer 5

Daily interruption in sedation shows that there is reduced duration of mechanical ventilation, shortened stay in ICU, and reduced PTSD symptoms

Question 6

NMBAs should always be used with which other 2 medications?

Answer 6

Sedative and analgesic medications.

Question 7

What is the train of four?

Answer 7

It is a way in which peripheral nerves are stimulated. It involves 4 electrical impulses delivered usually to the ulnar nerve. When no muscular blockade is present there will be 4 distinct muscle twitched. # of twitches decreases as blockade increases. NMBA should be titrated to 1-2 twitches.

Question 8

What prophylactic measures should be taken prior to neuromuscular blockade?

Answer 8

Prophylactic eye care: Corneal abrasions may occur. Instill artificial tears and tape eyes shut.
VTE prophylaxis: UFH, LMWH, fondaparinux
Stress ulcer prophylaxis: Mechanical ventilation is an indication for stress ulcer prophylaxis and all patients on NMBAs should be prophylaxed against stress ulcers.

Question 9

What medications do the guidelines recommend for short term sedation, long term sedation and for patients requiring intermittent awakenings?

Answer 9

Short term sedation: midazolam
Long term sedation: lorazepam
Intermittent awakenings: propofol

Question 10

Explain the recommendations made by the 2002 SCCM clinical practice guidelines regarding NMBA selection?

Answer 10

Majority of patients can be managed effectively with pancuronium. However, this medication can cause increased HR and perhaps another agent should be chosen if increased HR is observed. Cisatracurium and atracurium for patients with hepatic or renal disease. Cisatracurium is seen in most hospitals.

Question 11

Which NMBAs belong to depolarizing and non-depolarizing drug classes? What are their brand names?

Answer 11

Depolarizing: Succinylcholine (Quelicin)

Non-depolarizing: atracurium, cisatracurium (Nimbex), pancuronium (Pavulon), rocuronium (Zemuron), vecuronium (Norcuron)

Question 12

What is the MOA of NMBAs?

Answer 12

Interfere with neurotransmission at nicotinic ACh receptors in the neuromuscular junction.

Question 13

MOA of benzos

Answer 13

Agonize GABA-A

Question 14

MOA of propofol

Answer 14

Increased activity at GABA-A by acting as an agonist. Also interacts with glycine, nicotinic, and muscarinic receptors

Question 15

MOA of dexmedetomidine

Answer 15

Central a2 agonist which decreases release of adrenergic neurotransmitters from adrenergic nerves

Question 16

MOA of suggamadex

Answer 16

Encapsulates the NMBA hydrophobic inner core and reverses effects of Only rocuronium and vecuronium)

Question 17

MOA of neostigmine

Answer 17

Reversible inhibitor of ACh esterase which prevents breakdown of ACh and thus reverses effects of NMBAs

Question 18

MOA of flumazenil

Answer 18

GABA antagonist. Benzo reversal agent

Question 19

Adverse effects of NMBAs, sedating agents, and reversal agents

Answer 19

NMBAs: Hypotension, bronchospasm, and cardiac disturbances
Sedation agents:
Benzos: respiratory depression, hypotension, delirium
Propofol: Resp. depression, hypotension and bradycardia
Precedex: Hypotension and bradycardia
Reversal agents:
Suggamadex: Bradycardia, cardiac arrest, hypersensitivity, N/V, hypotension, HA
Neostigmine: Bradycardia, arrhythmias, N/V, increased GI motility, excessive secretions and bronchospasm
Flumazenil: Seizures

Question 20

What is the difference between depolarizing and non-depolarizing NMBAs?

Answer 20

Depolarizing: Agonize ACh recepors in the same manner as ACh but cause the ion channel to be open for a longer period of time. They are resistant to degradation by AChe which leads to repeated depolarization of postsynaptic nerve terminals. Excessive depolarization leads to desensitization because motor end plate is unable to repolarize (no AP firing).
Non-depolarizing: Competes with ACh for binding to nicotinic ACh receptors. Produce skeletal muscle paralysis.

Question 21

Differentiate between amino steroidal and isoquinolone non depolarizing NMBAs with regard to suggamadex reversal

Answer 21

Suggamadex is selective for the amino steroidal non-depolarizing NMBAs (rocuronium and vecuronium)

Question 22

Explain the clinical relevance of quaternary amine chemistry in NMBAs and neostigmine

Answer 22

All NMBAs act at skeletal muscle in the peripheral nervous system. The quaternary amine structure prevents these drugs from crossing the BBB which means no CNS effects.

Question 23

Explain the chemistry of succinylcholine

Answer 23

It is 2 ACh molecules linked together. They still have affinity for ACh receptors but resist degradation by esterase.

Question 24

Explain the pharmacokinetic properties and the advantages and disadvantages of continuous IV infusion and IV push administration

Answer 24

Continuous infusion: No peaks or troughs, allows for precise dose titrations, over sedation can occur due to accumulation
IV push: Peak concentration decreases over time until next dose, allows for administration of lowest effective dose, dose stacking may occur when repeated administration of push doses occurs

Question 25

Which medications can be given continuous IV infusion? IV push?

Answer 25

Continuous infusion: Benzos, precedex, NMBAs, propofol

IV push: Benzos, propofol* and NMBA* (*for procedures only)

Question 26

Describe the toxicologic issues that arise from use of IV lorazepam

Answer 26

The IV formulation requires PG to maintain solubility. PG has been associated with increased SCr, increased anion gap (acid, base disorder), and increased osmolar gap

Question 27

Identify the pharmacokinetic model used to describe propofol

Answer 27

3 compartment model: Blood, CNS, non-CNS extravascular tissue. It requires a much longer time to reach equilibrium which accounts for long half-life and short duration of action. This may explain PRIS.

Question 28

What is the difference between the 1 and 2 compartment models of pharmacokinetics?

Answer 28

One compartment: Drugs rapidly equilibrate with the tissue component.
Two compartment: Drugs slowly equilibrate with the tissue compartment.

Question 29

What is PRIS?

Answer 29

Propofol Infusion Syndrome
Mortality rate may be as high as 30% when used for > 3 days and at high doses
Symptoms of PRIS: Metabolic/lactic acidosis, cardiac arrhythmias, rhabdo, hypotension, AKI, hyperkalemia, hyperlipidemia, hepatomegaly

Question 30

How is propofol formulated?

Answer 30

Very lipophilic and must be formulated in soybean oil, glycerol and purified egg phosphatide to maintain solubility

Question 31

Explain the administration requirements of propofol

Answer 31

When given as continuous IV infusion, it must be administered through a dedicated IV line, must not hang for > 12 hours, and if transferred from original container, must be discarded within 6 hours.

Question 32

What is stress related mucosal damage and when does it occur?

Answer 32

It is the erosive process that occurs in the gastroduodenem when there is high physiologic demand (critical illness).
Occurs in 75-100% of patients and usually occurs within 1-2 days of admission to ICU.

Question 33

Explain the pathophysiology in which SRMD occurs?

Answer 33

Physiologic stress leads to mucosal ischemia (decreased oxygen delivery and decreased mucosal defense mechanisms). This leads to cell damage and ulceration.

Question 34

What are the indications for stress ulcer prophylaxis?

Answer 34

Mechanical ventilation, coagulopathy (INR <1.5, platelets < 100,000), shock or severe sepsis, burns covering >25-35% ob body, multiple trauma, severe head or spinal cord injury, >250mg hydrocortisone equivalent steroid use, history of recent GI bleed

Question 35

Given the brand or generic name recommend appropriate dose for SUP

Answer 35

Omeprazole 40 mg daily.
Pantoprazole 40 mg daily.
Esomeprazole 40mg daily
Famotidine 20mg BID
Ranitidine 150 BID
Omeprazole PO only. All the others are PO or IV.

Question 36

Compare and contrast neostigmine and sugammadex

Answer 36

Sugammadex reverses rocuronium and vecuronium. Sugammadex is faster at reversing NMBAs compared to neostigmine (2 mins vs 25 mins). Suggamadex has a more favorable side effect profile.
Neostigmine is not effective in deep neuromuscular blockade while sugammadex works against all severity of blockade.

Question 37

Why is flumazenil not routinely used?

Answer 37

Benzo overdose rarely results in death and it can better be managed with mechanical ventilation. Also, it doesn’t reverse the respiratory depression associated with benzo overdose. It has a short half-life and patients usually experience re-sedation after use of flumazenil. Also, it increases the risk of seizures.

Question 38

Explain the sedation recommendations referenced in the SCCM clinical practice guidelines

Answer 38

Benzo sedation is associated with an increased length of stay in the ICU.
Propofol favored over lorazepam and
Precedex favored over midazolam to limit the duration of mechanical ventilation.
Benzos cause more delirium compared to Precedex. Benzos however remain important in managing agitation, seizures, alcohol withdrawal.

Question 39

Which sedation scale is recommended for assessment of depth and quality of sedation

Answer 39

Richmond Agitation Sedation Scale (RAAS)

Question 40

What do the guidelines say about daily sedation interruption?

Answer 40

Daily sedation interruption or a light target level of sedation be routinely used in mechanically ventilated ICU patients.

Question 41

What is the difference between autonomic and somatic nervous systems?

Answer 41

Autonomic includes the sympathetic and parasympathetic branches of the nervous system and is involuntary control meaning this system works automatically.
The somatic nervous system is under voluntary control.

Question 42

Where does neurotransmission occur?

Answer 42

The motor end plate at the neuromuscular junction.