Sedatives and Analgesics

The aim of sedation is to have the patient alert and calm on minimal medications.
This can be achieved by:
charting sedation and analgesia to a sedation score
using ventilation modes which promote synchronous breathing (SIMV, CPAP
with pressure support)
use of regional analgesia techniques where appropriate
use of a tracheostomy
Desirable effects of sedatives and analgesia
1. Relieve anxiety
2. Provide adequate level of analgesia
3. Decrease physiological responses to pain and anxiety such as
a. Hypertension and tachycardia
b. Increased myocardial and cerebral oxygen consumption
4. Allow sleep
5. Enhance tolerance of endotracheal tube and ventilator synchrony
6. Allow invasive therapies and procedures
7. Provide a mechanism to control intracranial pressure
8. Reduce respiratory muscle oxygen consumption
Potential adverse effects of sedatives and analgesics in ICU
1.
2.
3.
4.
5.
6.
7.
8.

Respiratory depression
Prolonged ventilation
Increased risk of nosocomial infections
Emergence delirium
Hypotension
Gastroparesis and feed intolerance
Increased risk of venous thrombosis
Increase number of ventilator days and increased cost

Approach to sedation
1. It can be difficult to obtain a balance between an awake and distressed
patient and an oversedated and unconscious patient.
2. Infusions are preferred and maintain constant levels rather than peaks and
throughs
3. Infusions are titrated to clinical effect.
4. There can be marked inter-individual variability and dosing can be very
variable.
5. Patients with renal or hepatic dysfunction may require lower doses
6. Oversedation is more difficult to assess than undersedation
7. If the patient becomes oversedated, half the sedation rate
8. If still oversedated when reassessed in an hour, half the rate again until
desired sedation is reached or sedation ceased

9. If the patient is undersedated, use a bolus of sedation/analgesia and

increase the rate. If still undersedated, repeat as necessary.
10. Use boluses to cover stimulating procedures or therapies.
The prescription, should target a level of sedation that is appropriate to the patients
disease process and phase of illness.
The following Richmond Agitation Sedation Scale has been adopted by DICM
RBWH.
Richmond Agitation Sedation Score
Score
Term
Description
+4
Combative
Overtly combative, violent, immediate danger to staff
+3
Very agitated
Pulls or removes tube(s) or catheter(s), aggressive
+2
Agitated
Frequent non purposeful movement, fights ventilator
+1
Restless
Anxious but movement not aggressive or vigorous
0
Alert and calm
-1
Drowsy
Not fully alert but has sustained awakening (eye
opening/eye contact) to voice for > 10 seconds
-2
Light sedation
Briefly awakens with eye contact to voice (<10
seconds)
-3
Moderate
Movement or eye opening to voice (but no eye contact)
sedation
-4
Deep sedation
No response to voice but movement or eye opening to
physical stimuli
-5
Unable to rouse No response to voice or physical stimulation
How to Perform Assessment
1. Observe patient If patient is alert, restless or agitated score 0 to 4+ based
upon their behaviour. If they are asleep they will be a 0
2. Verbal stimulation If patient is not alert, restless or agitated state their name
and ask them to open their eyes and look at the speaker. Score patient -1 to -3
upon their reaction.
3. Physical stimulation If patient does not respond to verbal stimulation
attempts should be made to provide noxious stimuli. Based on their response
score -4 to -5.

Sedatives
Drug
Midazolam

Dose
1-5mg IV bolus
1-20 mg/hr IV infusion

Pharmacology
Benzodiazepine
Hepatic metabolism
Renal elimination
T1/2 1.5-5hrs

Clinical notes
Amnestic
Sedative
Anxiolytic
Anticonvulsant

Diazepam

1-10mg iv bolus
5-10mg po bd-qid

Benzodiazepine
Hepatic metabolism
Active metabolite
T1/2 50-100hrs

First line anticonvulsant

Amnestic
Sedative
Anxiolytic

Large doses may be required

in acute alcohol withdrawal
Propofol

0.5-3mg/kg/hr IV
infusion
start at 3ml/hr and
titrate to effect
Max dose 4mg/kg/hr

Hindered phenol
Extrahepatic, extrarenal
metabolism
Variable half life
depending on length of
infusion from 3mins to
7hrs

Haloperidol

0.5-5mg IV bolus

Butyrophenone
Hepatic metabolism
T1/2 20hrs

Dexmetomidine 1mcg/kg IV loading

over 1 hour
0.2-0.7mcg/kg/hr IV
infusion

Selective alpha 2
agonist
Hepatic metabolism
T1/2 2hrs

Not an analgesic
Rare complication of propofol
infusion syndrome
metabolic acidosis,
rhabdomyolysis, heart failure
May cause significant lipid
load
Usually used for short term
infusions except when
there is a need for repeated
neurologic examination (Eg
closed head injury)
Can cause myocardial
depression and vasodilation
Major tranquilliser
Indicated for delirium and
agitation
Less respiratory compromise
Alpha blocking effects may
lead to hypotension
Prolongs QT, may induce
torsades
Sedative
Anxiolytic
Analgesic
Used for short term sedation
Decreases BP, lowers HR,
may cause transient rise in
BP

Analgesia

DRUG THERAPY (oral/iv/PR)

1. NSAID:
a. effective
b. CI: GI upset, renal dysfunction, CVS instability, bleeding tendency, head
injury, allergy
c. Oral: voltaren SR 100mg daily
d. IV: ketorolac 15mg BD for 2/7
2. Weak opioid:

Tramadol
a. Oral/ iv/ PR tramadol 50-100mg tds
b. SE: nausea, vomiting, dizziness
c. CI: concomitant MAOI, SSRI
3. Paracetamol:
a. Oral/ PR/IV : Panadol 1g qid (IV Paracetamol is 7000% more expensive than
enteral formulations so use PO/NG/NJ where possible)
b. CI: hepatic derangement
4. Opioid:
a. Improve pain score and vital capacity
b. Advantages:
Ease of administration and monitoring by nurse
Without risk of invasive procedure or need for specialized personnel
c. SE: respiratory depression, sedation, cough suppression
d. Morphine: iv PCA- loading dose required or iv morphine prn
e. Co-administration of laxatives should be considered where clinically
appropriate
5. Additional agents
a. Ketamine
Short acting, dissociative ananesthetic agent
Can cause disturbing hallucinations
Tends to preserve sympathetic tone
b. Clonidine
Decreases sympathetic tone
Causes drowsiness

PCA-(PATIENT CONTROLLED ANALGESIA)

Pump and supervision of orders via the acute pain service

When used appropriately, PCA is superior to intermittent I.V. injections of pain
medication as:
The patient experiences better pain relief by maintaining a steady serum level and
avoids the peaks and valleys of I.V. opioids given intermittently.
The patient maintains control over pain relief.
Using PCA may shorten the length of hospital stay after major surgery.
Typical prescription
PCA morphine, 1 mg/mL Dose: 1 mg Dose interval: 5 minutes
PCA Fentanyl, 10mcg/mL Dose 20mcg Dose interval: 5 minutes
Backgrounds are not commonly used, unless there is as background opiate
requirement (such as opiate dependance)
Problems with PCAs
Improper patient selection confused, respiratory failure, agitation

PCA by proxy nurse or relatives administering dose

Pump problems
Pump programming problems

Safety Monitoring
Monitor pain with pain scale/sedation score
Assess for sedation using minimal spoken and tactile stimulation. Over sedated
patients may respond to more vigorous stimulation.
Identify patient factors that may increase the risks of PCA, such as obesity or
low body weight, sleep apnoea, or asthma and monitor more frequently and
initiate additional safeguards (such as capnography/oximetry) as indicated.

Analgesic Pharmacology
Drug
Morphine

Dosing
1-5mg IV bolus
1-20mg/hr IV infusion

Pharmacology
Opioid
Hepatic metabolism
Active metabolite
Renally excreted
T1/2 3-5hrs

Fentanyl

10-100mcg IV bolus
10-200mcg/hr IV
infusion

Opioid
Hepatic metabolism
Renally excreted
T1/2 2-6hrs

Ketamine

0.5-2mg/kg IV bolus

NMDA antagonist
Hepatic metabolism
Effect 11-17mins
T1/2 2.5-3hrs

Clinical notes
Analgesic
Not amnestic
Can cause respiratory
depression, ileus,
constipation, nausea and
vomiting, urinary
retention
Prolong action with renal
failure
Analgesic
Chest wall stiffness
Initally short acting, but
duration of action
increases with ongoing
infusion
Analgesic
Amnestic
Dissociative anaesthetic
Bronchdilator
Less vasodilation
Emergence phenomena

C. REGIONAL ANALGESIA:
1. EPIDURAL ANALGESIA

The optimal modality of pain relief for thoracic and abdominal wall wounds
a. Advantages:
superior analgesia with increase in FRC, dynamic lung compliance, VC
and PaO2
reduction in airway resistance
change shallow breathing to near normal and reduce paradoxical chest
wall movement

 modify immune response

b. Disadvantages:
technically demanding, esp. distressed in pain
may mask intraabdominal injury
cause hypotension
CVS instability
side effect (nausea, vomiting, urinary retention, respiratory depression,
pruritis)
complication (dural puncture, epidural haematoma, spinal cord trauma)
Management of unsatisfactory epidural analgesia
Steps to follow in case of unsatisfactory epidural analgesia

1. Pain assessment
2. Review anaesthetic record and pain management record for history of epidural
analgesic: epidural insertion difficulty, analgesic efficacy and catheter depth
3. Test sensory level of epidural analgesia with ice: no sensory level, adequate
sensory level but not dense enough, patchy epidural block, unilateral block
4. Check epidural site for catheter depth for displacement
5. Check epidural catheter for kinking, blockage
6. Check epidural pump for drug delivery history and malfunction (no battery,
out of order, accidentally stopped)
7. Manage accordingly as follows
8. Epidural infusion rate increase and bolus should only be performed if
patient is haemodynamically stable
9. Monitor BP/P/SaO2 q5min for 30min then q1h every time an epidural
bolus is given or epidural infusion rate is increased
10. Consider change to iv PCA, epidural morphine and other analgesic adjunct if
analgesia still inadequate: paracetamol, NSAID and tramadol
Trouble shooting:
(a) No epidural analgesia:
Cause:
1. Catheter not in epidural space: intravenous, anywhere out of epidural space
2. Catheter kinking, blockage
3. Epidural machine malfunction
Management:

Exclude intravenous placement/migration of epidural catheter by withdrawing

epidural solution from catheter for blood. Remove epidural catheter if intravenous
placement/migration of catheter is suspected.
Remove epidural catheter if epidural catheter is already out of epidural space.
After consultation with the pain service give 3ml bolus of 0.25% bupivacaine and test
sensory level 15min later. Consider repeat bolus. If there is still no sensory block,
remove epidural catheter.
Change battery or epidural pump accordingly

(b) Unilateral epidural analgesia:

Cause:
1. Patient position
2. Anatomic or functional division of epidural space
Management: consult pain service:

Turn patient to opposite side if catheter in epidural space 3cm

Pull epidural catheter back 1 cm if catheter in epidural space >3cm

Give 5ml 0.1% bupivacaine +2.5ug/ml fentanyl as bolus +/-repeat
Consider increase epidural solution infusion rate by 2ml/hr (recommended rate of
infusion 0.25kg/kg/hr), epidural morphine or iv PCA+/-adjunct

(c) Patchy block or missed segment:

Cause:
1. Scarring or deformation of epidural space
2. Anatomical variations of epidural space
Management: consult pain service:

Give 5ml 0.1% bupivacaine+2.5ug/ml fentanyl as bolus +/- repeat

Consider increase epidural solution infusion rate by 2ml/hr (recommended rate of
infusion 0.25kg/kg/hr), epidural morphine or iv PCA+/-adjunct

(d) Epidural segmental level adequate, but block not intense enough
Cause:
1. Insufficient time for epidural block establishment
2. Insufficient rate of epidural infusion
3. Inadequate concentration of local aesthetic.
4. Loss of epidural solution through intervertebral foramina.
5. Patient perception of inadequacy of sensory block.
Management: Consult pain service:

Allow more time for development of block.

Give 5ml 0.1% bupivacaine+2.5ug/ml fentanyl as bolus +/- repeat
Consider increase epidural solution infusion rate by 2ml/hr (recommended rate of
infusion 0.25kg/kg/hr), epidural morphine or iv PCA+/-adjunct

2. THORACIC PARAVERTEBRAL BLOCK (CONTINUOUS)

Maybe used in thoracic surgery/trauma.

a. effective analgesia, resulting in improved respiratory parameters and ABG
b. Advantages:
avoid need for sedation and ventilation and allows continuous neurologic
assessment (especially in patents with head injury)
unilateral segmental blockade spare lumbar and sacral nerve root for
monitoring (especially in patients w/ concomitant lumbar spinal injury)
does not require palpation of rib, feasible for fractures of upper ribs
technically simple
lower incidence of complication like urinary retention and hypotension
c. Complications: hypotension, vascular puncture, pleural puncture,
pneumothorax, inadvertent epidural anaesthesia
3. INTERCOSTAL NERVE BLOCK

Maybe used in thoracic surgery/trauma

a. Improve peak expiratory flow rate and volume
b. Disadvantages:
Require multiple injection-painful
Time consuming

Predispose to local anaesthetic toxicity

Technically difficult for upper ribs
Complication: pneumothorax

4. INTRAPLEURAL

Maybe used in thoracic surgery/trauma

a. Advantages: less complication like hypotension, bladder and lower extremity
paresthesia and weakness
b. Disadvantages:
Significant amount of anaesthetic may be lost in presence of chest drain
(may require temporary clamping which may cause tension
pneumothorax)
Theoretically impair diffusion of anaesthetic in presence of haemothorax
Posture-dependent
Complication: pneumothorax

Muscle Relaxants (Paralysis)

Uses

Faciltate intubation and ventilation

Decrease ventilator patient dysynchrony
Allow cooling to lower ICP
Stop shivering
Decrease oxygen consumption

Drug
Dosing
Suxamethonium 1-2mg/kg IVB

Vecuronium

Rocuronium

Cisatracurium

Pancuronium

Pharmacology
Depolarising muscle
relaxant (MR)
Metabolised by
pseudocholinesterase
T1/2 4-8mins

Clinical notes
Rapid Onset
Rapid Offset
Hyperkalaemia risk
in
- Burns
- myopathy
- paralysis
Suxamethonium
apnea
Phase II block with
repeated doses
0.1mg/kg IVB
Aminosteroid
Onset 2-3mins
50-100 mcg/kg/hr IVI non depolarising MR May worsen ciritcal
(NDMR)
illness
Hepatic metabolism polyneuromyopathy
T1/2 31-80mins
0.5-1mg/kg IVB
Aminosteroid
Onset 60-90secs
0.3-0.6mg/kg/hr IVI
NDMR
May worsen ciritcal
Hepatic metabolism illness
polyneuromyopathy
0.2mg/kg IVB
NDMR
Theoretical risk of
1-2mcg/kg/min IVI
Hoffman
laudanosine
Elimination organ metabolite
independant
(neurotoxic) not
clinically relevant
0.05-0.1mg/kg IVB
NDMR
Long acting (60Renally eliminated
100mins)
Tachycardia from
vagolytic and
sympathetic action

Questions
1. Propofol is
a. Analgesic
b. can rarely cause metabolic acidosis
c. long acting
d. renally eliminated

2. Analegesics
a. morphine elimination is unchanged in renal failure
b. ketamine is an opiate
c. tramadol can interact with SSRIs
d. PCAs should be run with background infusions
3. Suxamethonium
a. is a long acting non depolarising muscle relaxant
b. is metabolised in the liver
c. is neurotoxic
d. can cause fatal hyperkalaemia
References
1. Sasada M, Smith S, Drugs in Anaesthesia and Intensive Care, Oxford Medical
Publications
2. Stelting, R, Pharmacology and Physiology in Anesthetic practice, Lippincott
Williams & Wilkins
3. Limbird, L, Hardman, J, Goodman & Gillmanss The Pharmacological Basis of
Therapeutics, Mc Graw Hill