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Sedation and Analgaesia Flashcards

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1
Q

Why does deep sedation only have a few indications and what are these

A

Deep sedation (with or without paralysis) is associated with increased mortality (? Study)

Indications for deep sedation
1. RICP
- decrease metabolic rate
- avoids straining and coughing
- reduces intracranial pressure

  1. Medical conditions
    - Status epilepticus not responding to usual Rx
    - Tetanus
  2. Hyperpyrexial syndromes
  3. Unusual forms of ventilation that require deep sedation
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2
Q

What are the problems associated with oversedation?

A

Acute:
CNS: Confounded neurological examination
RSP: Prolonged ventilation
CVS: Haemodynamic Instability
GIT: Stasis and feed intolerance
Immune suppression
PSYCH: Increased delirium

Chronic:
Long term: Post critical care illness risk

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3
Q

What are the benefits of appropriate and adequate sedation

A
  1. Ventilator days, Hospital/ICU length of stay, ICU costs
  2. Accidental extubation/line removal
  3. NMB + risk of critical illness myopathy/polyneuropathy
  4. Post ICU functional decline/PTSD/
  5. Sedative side effects
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4
Q

Describe the RASS assessment

A

Richmond Agitation Sedation Score

+4 Combative
+3 Very agitated
+2 Agitated
+1 Restless

0 Alert and Calm

-1 Drowsy with sustained eye contact
-2 Light sedation: No sustained eye contact
-3 Moderate sedation: No eye contact
-4 Deep sedation: Respond to physical stimulus
-5 Unrousable: no response to physical stimulus

Goal is 0 to -2

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5
Q

Summarise the principles of effective sedation in ICU

A

Non-pharmacological
1. Counselling. Touch. Family contact
2. Maintain normal sleep cycle

Pharmacological
1. Titrated
2. Short acting agents that don’t accumulate
3. Combine agents for minimum dosing of each
4. Bolus regimen for procedures
5. IV route preferred. PO and IM unpredictable absorption in ICU.
6. Less for encephalopathic patients and elderly
7. Daily spontaneous awakening trial - except if paralysed

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6
Q

Describe the loading and maintenance doses of Fentanyl in the ICU

A

Load
1 -2 ug/kg (25 -100ug)

Maintain
1 to 3 ug/kg/hour (50 - 300 ug /hour) with as needed intermittent boluses

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7
Q

Describe the onset and duration of an intermittent dose of fentanyl

A

Onset 3 minutes

Duration 30 to 60 minutes

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8
Q

Describe the advantages and disadvantages of using fentanyl in the ICU

A

ADVANTAGES
1. Potent analgaesic and sedative effect
2. Minimal CVS effect (relative lack histamine release)

DISADVANTAGES
1. Highly Lipophillic (Long context sensitive half time)
2. Chest wall rigidity with higher dosing
3. CYP hepatic metabolism
4. Dependence and tolerance

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9
Q

Describe the loading and maintenance dosing for morphine

A

Load
2 - 10 mg IV

Maintain
2 - 4 mg every 1 to 2 hours
OR
2 to 30 mg/hour infusion (usually 2 - 5mg/hour)

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10
Q

Describe the onset and duration of action of morphine

A

Onset 5 to 10 minutes

Duration 4 - 5 hours

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11
Q

What are the advantages and disadvantages of morphine in the ICU

A

ADVANTAGE
1. Non-CYP metabolism (glucoronidation)
2. Cheap

DISADVANTAGE
1. Accumulation in hepatic/Liver dysfunction
2. Histamine release and vagally mediated –> venodilation, hypotension, bradycardia
3. Dependence and Tolerance

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12
Q

What is the loading and maintenance dosing for remifentanil in the ICU

A

Load
1.5 mg/kg

Maintenance
0.5 to 15 ug/kg/hour (usually 1 - 10 ug/kg/hour) which is a 50ug/ml dilution at 2 to 10 ml/hour

Mix 2mg i(1 amp) n 40 mls to make 50ug/ml.

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13
Q

What is the onset and duration of remifentanil

A

Onset 1 to 3 minutes

Offset 5 to 10 minutes after cessation of infusion

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14
Q

What are the advantages and disadvantages of remifentanyl in the ICU

A

ADVANTAGES
1. Ultra-short acting
2. Plasma esterase clearance (safe kidney/liver impairment) to inactive matabolites

DISADVANTAGES
1. Anticipate pain upon abrupt cessation
2. Glycine excipient may accumulate in renal failure (glycine toxicity –> high ammonia with organ toxicity). Rare.

NB in patients requiring frequent neurological assessment or those in multiorgan failure

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15
Q

What is the mechanism of action of paracetamol

A

Multifactorial
1. Central COX-3 inhibition (effect on central processing of pain)
2. Possible peripheral selective COX 2 inhibition
3. Endocannabinoid modulation (mice)
4. Serotonergic effect (effects of paracetamol inhibited by 5 HT antagonists)

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16
Q

What is the maximum dose of paracetamol per day and what is the accepted toxic ingestion dose

A

Maximum dose = 4g/day

Toxic dose > 10g in 24 hours

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17
Q

How long does PO vs IV perfalgan take to work

A

PO: 30 to 60 minutes

IV: 5 to 10 minutes

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18
Q

What are the advantages and disadvantages of paracetamol in the ICU

A

Advantages
1. No dependence and tolerance
2. No antiplatelet effect
3. No GIT toxicity (NSAIDS)

Disadvantages
1. Lacks significant anti-inflammatory effect
2. IV administration takes 15 minutes
3. Hepatotoxicity in chronic or acute overdose
4. Interacts with warfarin - may prolong INR

Hepatic dysfunction - limit dose to 2 g/day max

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19
Q

What is the mechanism of action of ibuprofen

A

Non-selective inhibition of cyclo-oxygenase enzyme during the metabolism of arachidonic acid.

COX 1 is constantly active and has homeostatic role
- GI ulceration
- Acute Kidney Injury

COX 2 is induced by inflammatory cytokines
- Antiplatelet
- Anti-inflammatory

Analgaesic activity is mediated by both enzymes which produce eicosanoids (prostaglandins and leukotrienes).

Inflammatory eicosanoids are responsible for increasing the sensitivity of nociceptors, NSAIDS prevent this.

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20
Q

What is the dose of ibuprofen

A

400 mg every 4 hours

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21
Q

Whatis the onset and offset of action of ibuprofen

Study These Flashcards
A

Onset 30 minutes

Offset: 4 - 6 hours

22
Q

What are the advantages and disadvantages of ibuprofen in the ICU

Study These Flashcards
A

ADVANTAGES
1. No dependence and tolerance
2. Effective anti-inflammatory

DISADVANTAGE
1. Worsen renal function
2. Gastropathy (dose related)
3. Antiplatelet and bleeding
4. Can alter cardioprotective effect of aspirin
5. Bronchospasm in asthma

23
Q

When should NSAIDS be avoided

Study These Flashcards
A
  1. Renal impairment (and elderly)
  2. GI bleeding
  3. Platelet dysfunction
  4. Ischaemic heart disease
  5. Heart Failure
  6. Hypovolaemia
  7. Asthma
  8. Cirrhosis
24
Q

What is the mechanism of action of Gabapentin in pain

Study These Flashcards
A

Depress neuronal excitability through interactions with calcium channels.
1. Stimulate descending inhibition
2. Inhibit descending serotonergic facilitation

25
What is the dose of gabapentin in pain
PO: initially - 100mg tds Then PO: 1000mg to 3600mg per day in 3 divided doses
26
What are the advantages and disadvantages of Gabapentin in the ICU
Advantages 1. Effective for neuropathic pain 2. Low risk of drug interactions Disadvantages 1. Requires enteral administration 2. Scheduled dosing: individualized dosing titration over days to weeks. (variable oral bioavailability) 3. Side effects: sedation/dizziness/ataxia 4. Cannot stop abruptly due to risk of discontinuation symptoms 5. Dose adjustment needed for renal impairment
27
What is the mechanism of action of propofol
Propofol binds to the beta subunit of the post synaptic GABA A receptor where it causes inward directed chloride current that hyperpolarizes the postsynaptic membrane and inhibits neuronal depolarisation. Essentially a GABA A receptor agonist
28
What is the dose of propofol for use in the ICU
Infusion: Usually 50 to 200 mg/hour. Titrate to effect. Less than 4mg/kg/hour (PRIS syndrome)
29
Describe the onset and offset of propofol
Onset 1 to 2 minutes Offset: 3 to 10 minutes (depending on dose and duration)
30
Describe the metabolism and elimination of propofol
Metabolism is hepatic - Glucoronidation and sulphate conjugation. All metabolites are inactive and eliminated in urine which can give the urine a healthy green tinge.
31
Describe the clinical effects of propofol
1. Anaesthesia and sedation 2. Respiratory depression 3. Decreased CMRO2 4. Antipruritic 5. Antiemetic 6. CVS effects: - Indirect and result from SNS inhibition - Stable cardiac output - Decreased heart rate (blunted baroreceptor reflex) - Venodilation and vasodilation - Minimal effects on inotropy at normal therapeutic doses
32
What are the advantages and disadvantages of propofol in the ICU
Advantages 1. Potent hypnotic 2. Immediate onset 3. Rapid offset 4. Metabolism apparently unaltered in renal and liver dysfunction 5. Few drug interactions 6. Infusion is readily titratable to desired RASS minimizing risk of oversedation 7. Decrease ICP and CMRO2 8. Controls intractable seizures Disadvantages 1. Hypotension 2. Bradycardia 3. Respiratory depression 4. Elevated TGs 5. Infection site pain 6. PRIS
33
What is the mechanism of action of ketamine
NMDA-receptor antagonist with centrally mediated sedation and amnesia nnd spinally mediated analgaesia. Facilitates endogenous catecholamine release Co-administer BZP to mitigate neuropsychiatric side effects
34
Describe the dosing of ketamine in the ICU
Load or bolus 0.25 to 0.5 mg/kg (repeat as necessary to max of 2mg/kg in 30 minutes) Maintenance 0.05 to 0.4 mg/kg/hour (usually 10 - 20 mg per hour)
35
What is the onset and offset of ketamine
Onset 1 minute Offset 10 to 15 minutes (single dose)
36
What are the advantages and disadvantages of ketamine in the ICU
Advantages 1. Potent dissociative sedative-anaesthetic 2. Marked analgaesic properties 3. Maintains CO 4. No inhibition of resp drive 5. does not supress upper airway reflexes Disadvantages 1. SNS stimulation (O2 demand) 2. Cardiorespiratory depression with rapid administration of high dose 3. Neuropsychiatric effects 4. hypersalivation 5. Nausea and vomiting
37
What is the mechanism of action of dexmedetomidine
Central highly specific alpha 2 receptor agonist resulting in a negative feedback with reduced noradrenalin release from the presynaptic terminal resulting in sedation, anxiolysis and a mild analgaesic effect. Imidazole receptor effects are poorly understood
38
Describe how dexmedetomidine is dosed in the ICU
Load 1mcg/kg over 10 minutes if haemodynamically stabler Maintenance 1 ug/kg/hour. Start low and titrate up to effect every 30 minutes 0.2 - 1.5 ug/kg/hour
39
Describe the onset and offset of dexmedetomidine
onset - 5 minutes with loading dose - 15 minutes without loading dose offset 1 to 2 hours
40
What are the advantages and disadvantages of dexmedetomidine in the ICU
Advantages 1. Effective sedative sympatholytic with anxiolysis and analgaesia 2. Character and depth of sedation may permit critically ill and ventilated patient to be interactive and easily awakened yet comfortable 3. Can be used for patient not intubated and ventilated 4. Reduces shivering in the rewarming phase of hypothermia 5. Less likely to cause delirium than other agents Disadvantages 1. Potentially significant hypotension and bradycardia that do not resolve quickly upon abrupt discontinuation. 2. Hepatic metabolism ( dose reduction recommended in liver and renal disease) 3. Rapid admin of loading dose can lead to haemodynamic instability or dysrhythmia. 4. Does not induce deep sedation needed for neuromuscular blockade
41
What is the mechanism of action of the benzodiazepines
Allosteric modulation of the GABA A receptor which potentiates the effect of GABA at these receptors to increase the inward chloride current resulting in hyperpolarization of the neruonal cell membrane.
42
Summarise the dose, onset, offset, route of administration of midazolam, lorazepam, diazepam
Midazolam - load: 1 - 4 mg IV - maintain: 2 - 8 mg/hour - onset 5 mins - offset: 30 mins Lorazepam - load: 1- 2 mg - maintain: 1 - 10 mg/hour - onset: 15 - 20 mins - offset: 6 - 8 hours Diazepam - load: 5 - 10 mg - maintain: Infusion contraindicated d/t extremely prolonged context senstiive half time. - Onset: 5 mins - Offset: 20 to 60 mins
43
What are the advantages and disadvantages of midazolam in the ICU
Advantages Sedative Amnestic Anxiolytic Anticonvulsant Immediate onset and short duration Propylene glycol free (infusion ok) Disadvantages CYP3A4 to active metabolites therefore drug interactions and Accumulation in liver and renal impairment Risk of delirium Need gradual titration and caution in elderly
44
What are the advantages and disadvantages of lorazepam in the ICU
Advantages Sedative Amnestic Anxiolytic Anticonvulsant Immediate onset and short duration Glucuronidation to inactive metabolites Low risk for drug interactions Safety in mild to moderate renal/liver dysfunction Disadvantages Slower onset Risk of oversedation due to overdosing in delayed response Accumulation in peripheral tissues Risk of delirium IV incompatibilities and risk of line precipitate Propylene glycol - risk of met acidosis with infusion Need gradual titration and caution in elderly
45
What are the advantages and disadvantages of Diazepam
Advantages Rapid onset Potent sedative Muscle relaxant effects Disadvantages CYP3A4 to active metabolites may accumulate in liver/renal dysfunction Risk of delirium Drug interactions Propylene glycol - accumulation --> met acidosis Injection site pain and phlebitis (limited use IV)
46
What is the dose of haloperidol in the ICU
1 to 10 mg every 6 hours
47
What is the onset and offset of haloperidol
Onset 5 to 20 minutes Offset 1 to 6 hours
48
What are the advantages of haloperidol in the ICU
Advantages Control hyperactive delirium and moderately sedating Minimal CVS effects Disadvantages CYP3A4 and 2D6 transformation QT prolongation EPSE NMS (higher risk with oral)
49
What is the dose of Olanzepine in the ICU
Bolus IM 5 - 10 mg repeat every 2 to 4 hours as needed Maintenance PO 5 - 10 mg daily (Max 20 mg/day)
50
What is the onset and offset of IM olanzepine
Onset 15 to 45 minutes Offset > 2 hoursW
51
What are the advantages and disadvantages of olanzepine in the ICU
ADV Lower risk EPSE and QT prolong DISADV Adverse effects - Orthostatic hypotension - Hyperglycaemia - Somnolence - QT prolongation - Prolonged half life in liver/renal dysfxn/older and female (Can be > 50 hours)
52
What are the doses of naloxone and flumazenil
Naloxone 400 ug bolus IV Flumazenil 400 ug bolus both have short half life (20 mins) and therefore wear off quicker than opioids and benzos

Intensive Care (22 decks)

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