Sedation and Analgaesia Flashcards
Why does deep sedation only have a few indications and what are these
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
- Medical conditions
- Status epilepticus not responding to usual Rx
- Tetanus - Hyperpyrexial syndromes
- Unusual forms of ventilation that require deep sedation
What are the problems associated with oversedation?
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
What are the benefits of appropriate and adequate sedation
- Ventilator days, Hospital/ICU length of stay, ICU costs
- Accidental extubation/line removal
- NMB + risk of critical illness myopathy/polyneuropathy
- Post ICU functional decline/PTSD/
- Sedative side effects
Describe the RASS assessment
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
Summarise the principles of effective sedation in ICU
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
Describe the loading and maintenance doses of Fentanyl in the ICU
Load
1 -2 ug/kg (25 -100ug)
Maintain
1 to 3 ug/kg/hour (50 - 300 ug /hour) with as needed intermittent boluses
Describe the onset and duration of an intermittent dose of fentanyl
Onset 3 minutes
Duration 30 to 60 minutes
Describe the advantages and disadvantages of using fentanyl in the ICU
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
Describe the loading and maintenance dosing for morphine
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)
Describe the onset and duration of action of morphine
Onset 5 to 10 minutes
Duration 4 - 5 hours
What are the advantages and disadvantages of morphine in the ICU
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
What is the loading and maintenance dosing for remifentanil in the ICU
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.
What is the onset and duration of remifentanil
Onset 1 to 3 minutes
Offset 5 to 10 minutes after cessation of infusion
What are the advantages and disadvantages of remifentanyl in the ICU
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
What is the mechanism of action of paracetamol
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)
What is the maximum dose of paracetamol per day and what is the accepted toxic ingestion dose
Maximum dose = 4g/day
Toxic dose > 10g in 24 hours
How long does PO vs IV perfalgan take to work
PO: 30 to 60 minutes
IV: 5 to 10 minutes
What are the advantages and disadvantages of paracetamol in the ICU
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
What is the mechanism of action of ibuprofen
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.
What is the dose of ibuprofen
400 mg every 4 hours
Whatis the onset and offset of action of ibuprofen
Onset 30 minutes
Offset: 4 - 6 hours
What are the advantages and disadvantages of ibuprofen in the ICU
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
When should NSAIDS be avoided
- Renal impairment (and elderly)
- GI bleeding
- Platelet dysfunction
- Ischaemic heart disease
- Heart Failure
- Hypovolaemia
- Asthma
- Cirrhosis
What is the mechanism of action of Gabapentin in pain
Depress neuronal excitability through interactions with calcium channels.
1. Stimulate descending inhibition
2. Inhibit descending serotonergic facilitation
What is the dose of gabapentin in pain
PO: initially - 100mg tds
Then PO: 1000mg to 3600mg per day in 3 divided doses
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
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
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)
Describe the onset and offset of propofol
Onset 1 to 2 minutes
Offset: 3 to 10 minutes (depending on dose and duration)
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.
Describe the clinical effects of propofol
- Anaesthesia and sedation
- Respiratory depression
- Decreased CMRO2
- Antipruritic
- Antiemetic
- 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
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
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
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)
What is the onset and offset of ketamine
Onset 1 minute
Offset 10 to 15 minutes (single dose)
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
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
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
Describe the onset and offset of dexmedetomidine
onset
- 5 minutes with loading dose
- 15 minutes without loading dose
offset
1 to 2 hours
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
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.
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
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
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
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)
What is the dose of haloperidol in the ICU
1 to 10 mg every 6 hours
What is the onset and offset of haloperidol
Onset
5 to 20 minutes
Offset
1 to 6 hours
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)
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)
What is the onset and offset of IM olanzepine
Onset 15 to 45 minutes
Offset > 2 hoursW
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)
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