Sedation, Analgesia and Paralysis in the ICU

Sedation, Analgesia and Paralysis
in the ICU
Ruth Forrest
Lead Clinical Pharmacist
Theatres, Anaesthetics and Critical Care
NHS Greater Glasgow and Clyde
Western Infirmary, Glasgow
Aims
• Why sedate patients in ICU?
– Properties of the ideal sedative agent
• Difficulties in monitoring sedation
– Sedation scores
– Paralysed patients
• What agents can be used
Sedation and Analgesia in the
Intensive Care Unit
• Why sedate patients in ICU?
– Properties of the ideal sedative agent
• Difficulties in monitoring sedation
– Sedation scores
– Paralysed patients
• What agents can be used
Why sedate?
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Enhances action of analgesics
Reduces anxiety and distress
Allows sleep
Produces amnesia
Facilitates ventilation
Properties of Ideal Sedative
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Anxiolytic
Somnolent
Analgesic
Respiratory depressant
No accumulation problems
No effects on haemodynamics
Amnesic properties
Suppress gag reflex
Anti-tussive /reduce bronchospasm
Problems of undersedation
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Agitation and patient distress
Failure to control pain
Removal of lines by patient
Poor ventilation – patient “fights”
ventilator
• Hypertension
• Tachycardia
Problems of oversedation
• Excessively prolonged sedation –
exacerbated in renal or hepatic failure
• Respiratory depression
• Haemodynamic disturbances – negative
inotropic effects and hypotension
• Immunosupression
• GI stasis – opiods
• Excess cost!
Sedation scoring
• Designed to ensure quality and cost-efficacy
– Allow dose titration of sedative agents
– Avoid inappropriate under or over sedation
• Numerous scoring systems available
– Non-comparable data from different centres and
trials
• Ramsay scale* Sedation – Agitation Scale†
• Simple vs Complex
– Subjective vs Objective, accurate & reliable
MA, et al. Br Med J 1974; 2: 656-9
†Riker RR,et al. Crit Care Med 1999; 27: 1325-1329
*Ramsay
Ramsay Sedation Scale
Score
Awake levels (observed)
1
Patient anxious and agitated or restless or both
2
Patient co-operative, orientated and tranquil
3
Patient responds to commands only
Asleep levels (response to a light glabellar tap or a loud
auditory stimulus)
4
Brisk Response
5
Sluggish Response
6
No response
Sedation - Agitation Scale
Score
Description
Example
+3
Immediate threat to safety
+2
Dangerously agitated
Pulling at ET tube or catheters, trying to
climb over bedrail, striking at staff
Requiring physical restraints and frequent
verbal reminding of limits, biting ET tube,
thrashing side to side
+1
Agitated
Physically agitated, attempting to sit up,
calms down to verbal instructions
0
Calm and co-operative
Calm, arousable, follows commands
-1
Oversedated
Difficult to arouse or unable to attend to
conversation or commands
-2
Very oversedated
Awakens to noxious stimuli only
-3
Unarousable
Does not awaken to any stimuli
Richmond Agitation-Sedation Scale (RASS)
Score
Term
Description
+4
Combative
Overtly combative or violent: Immediate danger to staff
+3
Very Agitated
Pulls on or removes tubes or has aggressive behaviours
towards staff
+2
Agitated
+1
Restless
Frequent non purposeful movement or patient –ventilator
dyschinchrony
Anxious or apprehensive but movements not aggressive or
vigourous
0
Alert and Calm
-1
Drowsy
-2
Light Sedation
-3
Moderate Sedation
-4
Deep Sedation
-5
Unarousable
Not fully alert but has sustained awakening, with eye contact
to voice
Briefly awakens with eye contact to voice (less than
10seconds)
Any movement (but no eye contact) to voice
No response to voice, but any movement to physical
stimulation
No response to voice or physical stimulation
Methods of Sedation
Intermittent boluses
or
Continuous infusion?
Daily cessation of sedation
• Oversedation prolongs ICU & hospital stay
– Impairs ability to conduct neurological assessment
• Daily interruption until patients were awake
– Versus interruption at the clinician‟s discretion
• Median duration of
– Ventilation
4.9 days vs 7.3 days (p=0.004)
– ICU stay
6.4 days vs 9.9 days (p-0.02)
• Diagnostic tests for changes neurological status
– 9% vs 27% (p=0.02)
• Unplanned extubations
– 4% vs 7% (p=0.88)
• Unknown psychological effect
Kress JP, et al. N Engl J Med 2000; 342(20): 1471-7
SEDATION HOLD
* Turn off sedative agents
and opiate analgesia
together
Are there any contraindications to a sedation hold?
Ensure low patient
activity levels
Ensure environmental
noise minimal
No
Contraindications
Continuous Infusion of muscle relaxants
02 up 60%
Reverse I:E ratio
PEEP high > 12.5
Pt raised intracranial pressure
Pt not on sedation
Observe patient
Assess sedation score
and document
YES
Patient agitated and
sedation score not achieved
Pt achieves target
sedation score without
requiring sedation
Do not restart sedation
Continue patient observation
Re-assess every 12 hours
Give bolus and restart sedation and
analgesia at half previous rate initially
Increase as required to achieve
target sedation score
* If patient in pain, do not turn off analgesia. Give analgesia as required.
Sedation score should be set by Medical & Nursing staff in the morning.
Maintain patient safety, comfort & anxiety levels at all times – continually reassuring patient.
Hypnotic-based sedation
A common approach to sedation over the
past 20 years is the use of hypnotic drugs to
sedate the patient to a desirable level
considered appropriate by the ITU team
• Sedation to the point of unconsciousness
results in patients being unable to express
any discomfort and pain
• Thus difficult to objectively assess discomfort
and pain experienced by the patient
Analgesic-based sedation
A patient centred approach focussing on the
analgesic needs of patients
• Addition of a sedative only if necessary
• Unlike hypnotic based sedation, analgesic
based sedation enables analgesic and
sedative to be adjusted to the patient‟s
expressed needs, rather than the needs
perceived by the ITU team
Preventing VAP Care Bundle
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Review Sedation and if appropriate stop each day
Assess for weaning and extubation each day
Aim to have patient at least 30o head up day
Daily mouth care – Chlorhexidine (or SDD if your unit
uses that)
• Subglottic secretion drainage in patients likely to be
ventilated for more than 48 hours
www.sicsag.scot.nhs.uk
Ventilator Bundles
• Elevation of the head of the bed
• Daily “sedation holidays” and
assessment of readiness to extubate
• Stress ulcer disease prophylaxis
• Deep venous thrombosis prophylaxis
Morphine
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Analgesic
Some sedative properties
Respiratory depressant
Hepatically metabolised
– M3G and M6G (40 x activity of morphine)
Metabolites accumulate in renal failure
Induces release of histamine from mast cells
Reduces GI Motility
Dose range 1-10mg/hr, bolus 1.5-5mg 2-4h
Inexpensive
Alfentanil
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Dose 0.5 to 5mg per hour
Half life 15 to 60minutes
Potent opiate
Hepatically metabolised/metabolites
inactive
• Potent respiratory depressant
Fentanyl
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100 x more potent than morphine
Dose 100-800mcg per hour
Half life 30 to 60mins
Hepatically metabolised, 8% renally
excreted
Synthetic Opiates do not cause histamine
release
Remifentanil
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Synthetic opiod with very rapid offset
Half life – 0.7-1.2 minutes
Must be given by continuous infusion
Metabolised by tissue esterases so clearance
independent of renal and hepatic function
• Short duration of action may be beneficial in
patients requiring interruptions for
neurological examination
• Expensive
Propofol
• Enhances GABA binding to receptors
• Rapid onset of action and short plasma half
life
• Hepatically metabolised /renally cleared
• Anti-tussive and reduces bronchospasm
• Central or peripheral administration
• Formulated in soya bean oil (no preservative)
• Reduces BP and cerebral perfusion pressure
• Tolerance develops rapidly
Midazolam
• Acts on specific benzodiazepine (GABA) receptors
• Rapid onset of action (5 minutes) and „perceived‟
short plasma half life (quoted as 45 minutes)
• Amnesic and anxiolytic properties
• Less haemodynamic effects than propofol
• Dose range 1-20mg per hour, 2.5-10mg bolus
• 96% protein bound
• Hepatically metabolised and renally excreted
– active metabolites α hydroxymidazolam
• Major contributor to over-sedation
Lorazepam
• Dose range 1-10mg per hour or 1-4mg q2-8h
• Oral preparation available
• Longer onset of action and half life
– Time to onset of action iv 5-10 mins po 20-30 mins
– Peak effect
iv 15-20 mins po 60-40 mins
– Half-life
~12 hours
• Metabolised by glucuronidation to inactive
metabolites
• Useful in long term patients and weaning
Haloperidol
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Indicated for agitation with psychosis /delirium
„Locked-in‟ syndrome
Extrapyramidal effects
Also a-opiate, a1-adrenergic, 5-HT and muscarinic
Trial initially with small doses
– 2.5-5.0 mg iv prn
Clonidine & Dexmedetomidine
 a2 agonists - a2 > a1 (300:1)
– Central effect (locus ceruleus)
– Spinal cord effect
– Peripheral vasculature
 Sedation
 Sympathetic activity
 Analgesia
 vasoconstriction (transient)
Clonidine
Dexmedetomidine
Onset of action
30-60 mins
30 mins
Time to peak activity
2 -4 h
90 minutes
Half-life
20-25 h
2-5 h
Vd (L/kg)
2.0
1.5-1.8
Protein binding
20-40%
94%
Metabolism
40% hepatic oxidation
No active metabolites
100% hepatic (glucoronidation and
cytochrome P450 hydroxylation)
Excretion
60% renal (unchanged)
40% hepatic
95% renal
5% faeces
Typical dosage range
75-150 mcg prn 2-6 hourly
50-150 mcg/h
1 mcg/kg loading dose followed by
0.2-0.7 mcg/kg/min
Dexmedetomidine
• PRODEX and MIDEX studies compared
dexmedetomidine vs propofol and midazolam
• Primary endpoints were depth of sedation and
duration of mechanical ventilation
• Non inferior in both trials in maintaining depth of
sedation
• No difference in length of stay
• Patient rousability and ability to communicate was
better with dexmedetomidine
• Hypotension and bradycardia more common with
dexmedetomidine than midazolam
Ketamine
• Blockade of ionic channels opened by NMDA
receptors
• Dissociative anaesthesia
– Concurrent infusion of midazolam for amnesic effect
• Analgesic
• Sympathetic agonist
– ↑BP ↑HR and ↑CO
• Suggested dose range of 1.0 – 2.5 mg/kg/h
Weaning from Ventilator
• Ensure cause of, and any complications
arising from, respiratory failure have been
corrected
• Eradicate sepsis
• Correct nutritional status and fluid and
electrolyte balance
• Withdraw sedatives
• Start when staffing is at it‟s best
• Discuss with patient
Paralysis (Neuromuscular
blockade)
• Facilitate mechanical ventilation if patients
can‟t tolerate even with appropriate sedation
• Multiple trauma if unstable fractures may cause
further damage to the viscera
• Critical gas exchange –may produce small
increase in lung compliance
• Tetanus
• Novel ventilation techniques
– High-frequency oscillation (HFO)
Neuromuscular Blocking Agents
• non depolarising
• histamine release may cause bronchospasm
• Paralysis associated with prolonged muscle
weakness (causality unclear)
• Hypokalaemia, hyperkalaemia,
hypophosphataemia and drugs (eg
gentamicin) may enhance paralysis
Pancuronium
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Long acting
Dose 4-8mg bolus 1-4mg per hour
Hepatically metabolised
Active metabolites excreted renally
Has vagolytic activity
May release histamine
Vecuronium
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Short duration of action
Dose 5-10mg bolus or per hour
Hepatically metabolised
Renally excreted
No histamine release
Atracurium
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Short duration of action
25mg to 75mg per hour
Hoffman elimination
Histamine release if given too rapidly
Rocuronium
• Active metabolite of Vecuronium
• Renally excreted
• Rapid onset of action
Cisatracurium
• Cis-isomer of atracurium
• Minimal histamine release
• Less laudanosine production
Properties of NMBAs
Drug
Ultra-short duration
Suxamethonium
Short duration
Mivacurium
Intermediate duration
Atracurium
Cisatracurium
Rocuronium
Long duration
Pancuronium
Onset
(min)
Duration
(min)
Recovery
index
(min)
Cardiovascular
effects
1-1.5
7-12
3-4
++
3-5
15-25
6-8
++
3-4
4-6
1.5-3
35-45
40-50
30-40
10-15
10-15
10-15
++
0
+
3-5
90-120
30-45
+++
“My recollection is of a constant feeling
of nausea and choking, made worse by
any movement of the head or body”
Shovelton,D, Intensive Care – A patient‟s view, J Drug Dev 2 (Suppl 2) 1989 15-18