Clinical Guideline

SEDATION AND ANALGESIA ON PICU

SETTING Paediatric Intensive Care Unit (PICU), Bristol Royal Hospital for Children

FOR STAFF Medical, pharmacy and nursing staff working on PICU

PATIENTS Children on PICU requiring sedation

_____________________________________________________________________________

INDEX

Summary flow sheet 2

Introduction 3

First line 3

Second line and when to change 5

Bolus doses 5

Comfort B Target Guidance 6

Weaning and withdrawal 6

Oral conversion 7

Alternative agents 7

Procedural sedation in extubated children 8

Comfort Score and Pain Assessment Flow Chart (Appendix A) 9

Comfort B (Appendix B) 10

FLACCS and NISS (Appendix C) 11

Sophia Observational Scoring Tool Flowchart (Appendix D) 12

Sophia Observational Scoring Tool (Appendix D) 13

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 Titrate to sedation target: Deep / Standard

Non-pharmacological measures: swaddling / soft restraints (for ETT safety not

sedation) / reduce noise / temperature / feeds / nasal ETT / cuddles / dummy

Morphine / Fentanyl +/- Midazolam / Clonidine

or chloral in neonates
Further 5
days
Unsafe airway Reaching max
OR active with doses or frequent Day 5
no distress boluses.

Add muscle Medical review: Change

relaxant Consider oral sedative +/-
agent / change of opiate or
agents earlier convert to oral
sedation

Over sedated: Standard Under sedated:

6-13 Comfort B: 14-19 20+

6-8: Seek medical Continue and Increase an agent

review and reassess up to a maximum
decrease an of 25%
agent by 50%

9-13: Decrease Medical review if

an agent by 25% reaching maximum
doses.
Consider adding oral
Medical review if reaching maximum doses. agents or changing
Consider adding oral agents or changing to alternate IV to alternate IV agent.
agent.

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INTRODUCTION

Children on intensive care can require analgesia (pain relief), sedation (reduced consciousness or
reduced response to painful stimuli) or more commonly both. Many of our agents have both
properties to some extent, and there is some crossover of effect – a child whose pain is well
managed will often require much less sedation. Pain may be from surgery or procedures, and
ongoing discomfort from lines and drains. Ventilated children need to be able to tolerate an
endotracheal tube, and not pull out their lines and drains. Some children are sedated to remove
metabolic demands e.g. very poor cardiac function, traumatic brain injury. Muscle relaxants
(“paralysis”) may be added but provide neither sedation nor analgesia. Assessment of pain and
sedation can be challenging, the Comfort B score and pain tool flow chart will help with your
decision making (See Appendix A).
Examples of commonly used drugs on PICU are:

Analgesia only
• Paracetamol
• Non-steroidal anti-inflammatory drugs e.g. ibuprofen

Sedation only
• Benzodiazepines e.g. midazolam, lorazepam
• Propofol
• Chloral hydrate
• Antihistamines

Both analgesic and sedative effects

• Opiates e.g. morphine, fentanyl
• Alpha blockers e.g. clonidine, dexmedetomidine
• Ketamine

FIRST LINE

Remember non-pharmacological interventions in all children e.g. swaddling, cuddles, noise and
light reduction especially at night/quiet time, oral sucrose in neonates, dummies. Restraints can
also be used with parental permission to allow children some movement but not let them reach
tubes/lines. A nasal tube can be much better tolerated than an oral one and allow less sedation to
be used.

Most intubated children will initially be sedated with morphine, plus midazolam / clonidine or chloral
in neonates.

With the exception of Clonidine some of these drugs may need loading doses if the patient has not
yet been given any agents of the same class. Post-operative patients will have usually had some
opiates in theatre so may not need loading (check with the anaesthetist at handover and the
intraoperative drug chart).

Common side effects:

Morphine – respiratory depression, hypotension, histamine release
Midazolam – respiratory and cardiac depression, hypotension, paradoxical agitation
Clonidine – bradycardia (rarely problematic), hypotension

Midazolam is particularly associated with problematic withdrawal symptoms and a significant

number of children will get more agitated with increased dosing. It is therefore recommended to not

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use more than 200 micrograms/kg/hr – instead consider adding or changing agents. The same
principle applies if multiple boluses are being given.

Sedation should be titrated to Comfort B (see Appendix B) and can be utilised on patients of all
ages who are sedated but not muscle relaxed. The Comfort B target (Standard (14-19) / Deep (8-
13) or not applicable as muscle relaxed) should be documented on every invasively ventilated
patient and those needing active sedation management in the morning handover or morning
consultant ward round.

Every patient who is planned to be extubated in the morning should have a decision made on the
Night Ward Round regarding:
• If they are suitable for extubation overnight if they meet spontaneous breathing trail (SBT)
criteria and are otherwise ready for extubation.
• If there is a plan to wean sedation overnight there should be a sedation plan documented
regarding how to manage the child’s sedation if they become too mobile but are not for
extubation overnight. This patient group in particular may benefit from a period of time on
propofol prior to extubation.
• Nil by mouth time.

The patient should be observed for a 2 minute period and scored accordingly, with consideration to
behaviour / medications given in the last hour. Scoring should take place every 4-6 hours or when
sedation rates have changed or a bolus has been given.

Doses above morphine 40 micrograms/kg/hr and midalozam 200 micrograms/kg/hr should not be
routinely used for sedation, although opiate doses can be much higher in certain conditions e.g.
burns, palliative care and higher doses of midazolam are used for refractory seizures.

All children with a definite source of pain e.g. surgery should have paracetamol regularly unless
contraindicated. Ibuprofen should also be considered but contraindications/cautions are common
in the PICU population e.g. low platelets, use of high dose aspirin //warfarin/therapeutic dose
heparin, renal impairment (see the Cardiac Enhanced Recovery Programme guidance for
guidance on this patient group).

Muscle relaxants e.g. rocuronium, pancuronium, atracurium may be used in addition to analgesia
and sedation. Indications include severe lung disease, need for high frequency ventilation (HFOV)
and critical airway problem. They can be given as intermittent boluses or continuous infusions.
Atracurium is used in patients with significant renal impairment as it is not renally excreted unlike
the others in this class.

As muscle relaxants do not provide any sedative effect, children must not be distressed before
starting. They can however occasionally be used with a sedation sparing effect – for example a
child who is not distressed but moving a lot and has a difficult airway may be better having less
sedation and a muscle relaxant for a brief period instead of large doses of sedation and
subsequent withdrawal symptoms.

Be aware that assessment of neurology and comfort score are not possible, and oedema can be
problematic. Use of these agents can contribute to critical illness polyneuropathy.

ALL children on muscle relaxants should routinely have a daily hold (stop the infusion and wait for
movement, usually after morning ward round) unless the PICU consultant says otherwise.

There is no tool available to assess sedation levels in the muscle relaxed child, ALL children on
muscle relaxants should have hourly pupils and assessment of acute changes in haemodynamics.

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A child who is still distressed/agitated (but not in pain) on morphine and midazolam may have
chloral hydrate added. Use with caution in patients at high risk of NEC e.g. neonates with reduced
aortic flow due to coarctation. NB: Can cause hypotension.

For infants on non-invasive ventilation, clonidine or chloral can be useful if required to facilitate
tolerance of the NIV interface.

Oral sedation should be used as soon as possible, when the patient is tolerating enteral feeds.
Often this will be when they are more stable and weaning from sedation.

SECOND LINE AND WHEN TO CHANGE

Sedation should be routinely changed after approximately 5-7 days with the aim of reducing
tolerance and withdrawal. A change may be considered earlier in a child who has high comfort
scores on maximum first line agents. The most common used second line opiate and a switch
between Midazolam and Clonidine. Cycling sedation should not lead to more than 2 intravenous
agents running concurrently as the first should stop as the switched agent starts and does not
require weaning.

Fentanyl 1-2 micrograms/kg/hr (sometimes higher doses of 5-10 micrograms/kg/hr are used,
usually in patients with problematic pulmonary hypertension, must be discussed with a consultant).

Clonidine has very good bioavailability so the enteral route should be used whenever possible but
it can also be given as a continuous iv infusion. Causes bradycardia which can be marked but is
rarely problematic. Also see clonidine guideline.

Similarly, doses should be titrated to comfort score (see Appendix A); natural reduction in Comfort
Scores in the sleeping child should be considered prior to adjustments.

After a further 5-7 days on 2nd line agents the drugs should be changed again, often back to the
original agents.

Propofol infusions are used cautiously on PICU due to the risk of propofol infusion syndrome
(PRIS), a complication with a high mortality rate. However, it is a very effective sedative that will
completely wear off within minutes of stopping the infusion. Therefore, it can be used in selected
patients for periods of usually <24 hours at a maximum dose of 4mg/kg/hr. It can be useful in
children who are difficult to sedate but who will be extubated the following day. Also, in children
who have needed a lot of other sedation but need a rapid wake up clear of respiratory depressants
(often very little else will be needed while propofol is running so most other drugs can be stopped
rather than weaned). Regular gases are necessary to monitor for lactic acidosis and you should
ensure that the child is receiving adequate carbohydrate intake/glucose infusion. In general
propofol should be avoided for children with metabolic conditions or those on a ketogenic diet due
to increased risk of PRIS.

PRIS is characterised by one or more of:

• otherwise unexplained metabolic acidosis
• rhabdomyolysis
• ECG changes
with or without AKI, hyperkalaemia, lipidaemia, cardiac failure/hypotension, fever, elevated liver
enzymes, or raised lactate.
Propofol should be stopped immediately if PRIS is suspected.

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BOLUS DOSES

Bolus doses of sedation and opiates can be administered to achieve the desired comfort score.
The bolus doses should be prescribed by the medical team in the order instructions. If the child
requires more than 2 boluses in a 60minute period increase the sedation by 25% (do not exceed
max doses as detailed above) or consider adding an oral agent. A medical team review of the
patient sedation plan is required.

Morphine: 20 micrograms/kg (max 1 mg) – If the child is in pain, then consider loading with 50
micrograms/kg
Midazolam: 50 – 100 micrograms/kg (max 5mg)
Fentanyl: 1 micrograms/kg (max 50 micrograms)
Propofol: 1mg/kg

NB: Ensure IV access is patent.

ACHIEVING COMFORT B TARGET

• Every patient should have a set sedation target: Standard (14-19) / Deep (8-13)
documented in morning handover or consultant ward round.
• Scores outside of the target range should trigger a deeper assessment of cause and correct
it

FLACC for pain assessment

• Helps to differentiate between pain issue or sedation issue in patients with a COMFORT B
score above target
• Give a value from 0 to 2 in each category and apply scale with total value.
• Score >4 requires treatment

WEANING AND WITHDRAWAL

Many PICU patients have a short stay with only a brief period of sedation which can therefore be
stopped abruptly without withdrawal. It is unusual (but not impossible) to have symptoms of
withdrawal after less than 5 days on PICU. A Sophia score is used to assess and grade withdrawal
symptoms (see Appendix C). Withdrawal and delirium can appear very similar and confuse the
clinical picture, and signs and symptoms of withdrawal may be attributable to one or several drugs.

In order to prevent/ameliorate symptoms of withdrawal we will routinely make a gradual reduction

of dose for patients after 5-7 days of sedation. Clonidine can help manage symptoms of withdrawal
from other agents (see clonidine guideline).
Therefore, a suggested order of weaning is 1) benzodiazepines, 2) opiates, 3) clonidine. Each drug
can be weaned by 20% of the original dose daily for 5 days then stopped.

Weaning and withdrawal are not predictable so doses and weaning plans need reviewing daily with
Sophia scores (see Appendix D). Sometimes longer weans will be needed for patients who have
had large doses of sedation for long periods. For example, if a child has signs of withdrawal after
stopping a qds or tds wean, the same dose can be given, reducing the frequency every day.

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Small babies may need a very small dose that is practically hard to give, so if doses are below:

morphine 100micrograms
clonidine 0.25microgram
lorazepam 10micrograms

then prescribe the doses above but reduce the frequency daily until stopping (i.e. QDS, TDS, BD,
OD then stop).

Adolescent patients > 80kg should not usually exceed adult doses including oral morphine 10mg,
clonidine 100 micrograms.

Intubated children who are likely to have a longer PICU stay should have a routine reduction in
sedation of 10% per day.

ORAL CONVERSIONS

IV dose Example
Conversion factor Oral equivalent dose
micrograms /kg/hr
Oral clonidine QDS 0.8 micrograms/kg/hr
(Max 5 = 5 micrograms/kg oral
Clonidine x6
micrograms/kg or clonidine QDS
100micrograms)
No oral equivalent and no need to wean. If the patient needs oral
Dexmedetomidine sedation, prescribe clonidine at a maximum dose of 5 micrograms/kg
QDS
20 micrograms/kg/hr =
Oral morphine 4 160 micrograms/kg
Morphine x8
hourly oral morphine 4 hourly
Conversion to oral morphine is particularly unreliable and can result in
oral morphine doses far exceeding the recommended range, so fentanyl
Fentanyl should be weaned as much as possible first. Fentanyl patches are rarely
used as standard on PICU. Fentanyl running at 0.8microgram/kg/hour is
the equivalent of oral morphine 0.5mg/kg 4 hourly
30 micrograms/kg/hr =
Midazolam x0.5 Oral lorazepam 15 micrograms/kg oral
lorazepam QDS

ALTERNATIVE AGENTS

This is not an exhaustive list of either agents or side effects but aims to briefly describe other drugs
used intermittently on PICU.

Dexmedetomidine (see guideline) is an alpha blocker that is more centrally selective than
clonidine, although still causes notable bradycardia. Some analgesic and anxiolytic effects. Usual
therapeutic range 0.4-0.7micrograms/kg/hr. This agent is not recommended as procedural
sedation but can be useful for sedation in extubated children as it has no effect on respiratory
drive.

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Ketamine is more commonly used as an induction agent due to cardiovascular stability, but can
also be given as an ongoing sedative infusion. Sometimes used in asthma due to bronchodilator
properties. Increases secretions. Also used in complex/chronic pain patients.

Antihistamines e.g. promethazine as alternative oral agents.

Gabapentin used in patients with neuropathic or complex pain. Also in burns.

Remifentanil – opiate with very rapid onset and short half-life (hyperlink to guideline).

Methadone is sometimes used for a slow opiate wean. Not usually on PICU in Bristol but you may
see it in patients transferred from elsewhere.

Volatile anaesthetic agents (Sevoflurane or Isoflurane) via an Anaesthetic Conserving Device

(AnaConDa).

PROCEDURAL SEDATION IN EXTUBATED CHILDREN

Some children will need a brief period of sedation e.g. for a lumbar puncture or drain/line removal.
Normal anaesthetic fasting periods will apply prior to procedural sedation. Children will need
cardiac and respiratory monitoring during any sedation. Options include:

Distraction including oral sucrose in young babies.

Entonox – mixture of nitrous oxide and oxygen, child needs to be old enough to use the
mouthpiece, typically over 7 years although from 4 years in co-operative children.

Ketamine – good cardiorespiratory stability but will have sedative effects for several hours and can
increase respiratory secretions significantly.

Propofol – quick onset and short half-life but cardiac and respiratory depressant, no analgesic
effect.

Midazolam – provides amnesia but cardiac and respiratory depressant, no analgesic effect.

Morphine – needs to be given ~ 10 minutes before procedure or use Fentanyl - quick onset and
shorter half-life but both are cardiac and respiratory depressants.

RELATED Clonidine For Sedation And Withdrawal

Dexmedetomidine Paediatric Protocol
DOCUMENTS

AUTHORISING PIC Governance

BODY

SAFETY All sedative drugs are potentially dangerous and so use of this guideline
outside of the PICU / HDU area is not advised.
QUERIES Contact senior staff on PICU extension 28018 with any urgent queries.

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Appendix A

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Appendix B
COMFORT behaviour ©
scale

Behavioural Item Description Choose

one
Alertness Deeply asleep (eyes closed, no response to change in 1
environment)
Lightly asleep (eyes mostly closed, occasional responses) 2
Drowsy (child closes his/her eyes frequently, less responsive to 3
the environment)
Awake and alert (child responsive to the environment) 4
Awake and hyper-alert (exaggerated responses to 5
environmental stimuli)

Calmness/Agitation Calm (Child appears serene and tranquil) 1

Slightly anxious (child shows slight anxiety) 2
Anxious (child appears agitated but remains in control) 3
Very anxious (child appears very agitated, just able to control) 4
Panicky (severe distress with loss of control) 5

Ventilated Child No spontaneous respiration 1

Spontaneous and ventilator respiration 2
Restlessness or resistance to ventilator 3
Actively breathes against ventilator or coughs regularly 4
Fights ventilator 5
OR
Self Ventilating Quiet breathing, no crying sounds 1
Child or NIV Occasional sobbing or moaning 2
Whining (monotonous sound) 3
Crying 4
Screaming 5

Physical No movement 1
Movement Occasional , (three or fewer) slight movements 2
Frequent (more than three) slight movements 3
Vigorous movements limited to extremities 4
Vigorous movements including torso and head 5

Muscle Tone Muscles totally relaxed; no muscle tone 1

Reduced muscle tone; less resistance than normal 2
Normal muscle tone 3
Increased muscle tone and flexion of fingers and toes 4
Extreme muscle rigidity and flexion of fingers and toes 5

Facial Tension Facial muscles totally relaxed 1

Normal facial tone 2
Tension evident in some facial muscles (not sustained) 3
Tension evident throughout facial muscles (sustained) 4
Facial muscles contorted and grimacing 5

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Appendix C
FLACCS Pain Score

RESPONSE SCORE 0 SCORE 1 SCORE 2

Cry / Voice No complaint/ Consolable/ Not Inconsolable/complaining

no cry talking/ negative of pain

Facial Normal Short grimace <50% of Long Grimace >50% of

Expression time time

Posture Normal Touching, rubbing, Defensive/Tense/ rigid/

sparing arched

Movement Normal Reduced or restless Immobile or Thrashing

Colour Normal Pale Very Pale/ Green/Grey

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Appendix D

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