Pharm - Viva - Sedation

Question 1

What is remi

Answer 1

Synthetic phenylpiperidine derivative of fentanyl

Pure u agonist

White powder, 1,2,5mg reconstituted in saline

Metab - non-specific plasma and tissue esterases (but unlike sux, no affected by cholinesterase deficiency)
Duration is by elimination and not distribution

Question 2

Remi side effects

Answer 2

Resp - depression, chest wall rigidity

CVS - Brady and hypotension

Can be reversed by naloxone

Question 3

What receptor does remi act on

Answer 3

Pure u (mu) opioid receptor

Question 4

Remi metabolism

Answer 4

Non specific tissue and plasma esterase

Question 5

Why would you use remi in ICU

Answer 5

Rapid predictable offset once turned off due to short CSHT (3 minute)

Used in Neuro—crit care to assess neurology rapidly

Useful in difficult to wean patients, patients expected to extubate quickly, or to facilitate procedures

Question 6

Problems with remi use

Answer 6

Wears off rapidly - need alternative analgesia

Hyperalgesia intra-op, therefore need more opioids post op

Question 7

What is context sensitive half time

Answer 7

Time taken for plasma conc to halve, after an infusion designed to maintain constant blood levels is STOPPED

Context - duration of infusion (half time changes as duration progresses)

Question 8

What influences the range of CSHT

Answer 8

Ratio of:

Clearance due to redistribution to clearance due to elimination

Predicts how long a patient will wake up from steady state infusion

Fent - redistributes quickly, elimination is 20% of distribution. Therefore CSHT increases rapidly with infusion to 300 minutes max

Propofol - redistribution = elimination. Concentration falls rapidly. 20 mins CSHT

Remi - distribution lower the elimination (opp of fent). Elimination dictates clearance and is low and constant

Question 9

Propofol

Answer 9

2-6 di-iso-propylphenol
1 to 2% lipid emulsion. Soya bean oil and egg phosphatic
Lipid soluble. Not water soluble

Unionised at physiology (pKa = 11)
98% protein bound
Vd 4litres/kg

Rapid distribution so wears off after quick bolus

Hepatic metabolis to quinol - sulphate and glucuronide

Question 10

Adverse effects of propofol

Answer 10

Resp - depression and apnoea

CVS - Low SVR, hypotension
Brady
Reduced sympathetic activity

Met - PRIS

Other - green urine

Question 11

PRIS

Answer 11

Refractory bradycardia leading to asystole plus:

Unexplained met acidosis (BE > -10
Rhabdo /high CK, high K, AKI or myoglobinuruea
Lipaemic plasma (triglycerides)
Fatty liver/hepatomegaloy/liver dysfunction

Question 12

Patho phys of PRIS

Answer 12

Impaired mitochondrial fatty acid metabolism

Direct inhibition of mitochondrial function

Impaired oxygen utilisation, anaerobic resp and lactate production

Also myocardial depression and accumulation of unutilised fatty acid

Question 13

Risk for PRIS

Answer 13

High dose infusion >4mg/kg/hour

Young age (low glycogen stores, depend on lipid metab)

CI in ICU under 16

Brain injury
Low carb high lipid intake, TPN
Catecholamine, and steroids
Inborn mitochondrial disease

Question 14

PRIS presentation

Answer 14

Brady
Varying heart blocks
RBBB
Arrhythmia
Brigade - concave ST V1-3

Unexplained cardiovascular instability

Question 15

PRIS treat

Answer 15

Stop propofol
Start alternative agent - midaz

Support oxygen and haemodynamic
Treat rhabdo - urine to 2-3mls/hour, alkalinisation, diuretics, treat K)
RRT if AKI
Carbohydrate intake

Temporary pace
VA ECMO???

Question 16

Ways to assess sedation

Answer 16

Richmond Agitation Sedation Score (RASS)
Ramsey Sedation Scale

Richmond:
+4 to -5
+4 combative, -5 unrousable
0 alert and calm, 1 restless, -1 drowsy

Ramsey
1 to 6
1- anxious agitated restless
2 - cooperative
3 - commands only
…
6 no respond to glabellar tap

Question 17

What level of sedation?

Answer 17

Titration to clinical need and should be set as part of daily ward round

3 C rules - Calm, co-operative and comfy

RASS 0 to -1

Or -3 to -5:
Brain injury, raised ICP
Use of paralysis
ARDS
Vent dysynchrony
Immolbisation - spinal #
Status epilepticus