ADULT CRITICAL CARE GUIDELINES FOR SEDATION

AND ANALGESIA IN THE INTUBATED PATIENT

Contact name and job
title.

Dr T de Beer and Dr R Sherman

Consultants in Intensive Care Medicine and
Anaesthesia.
Critical Care, Queens Medical Centre.
Mid Trent Critical Care Network.

Directorate and
Speciality

Adult Critical Care Department, Nottingham

University Hospitals NHS Trust.

Date of submission
Date of review

November 2011
November 2013

Application

Adult intubated patients receiving sedation and

analgesia within adult critical care units at
Nottingham University Hospitals NHS Trust
This guideline describes the optimal choice of
sedative and analgesic in the intubated patient.

Abstract

Key words

Sedation, Analgesia, intubated patient.

Evidence base

Target audience

1b plus updating of current guidelines. Based on

Intensive Care Society sedation guideline
Critical Care Cross Town Protocol and Guideline
Group, Critical Care Directorate.
Dr D Selwyn, Head of Service Critical Care
B Lawrence, Matron Critical Care
Critical Care Cross Town Group
Critical care nursing and medical staff

Training Plans

In local areas as required

Audit Plans

Will be audited following implementation

Consultation process
Ratification

This guideline has been registered with the trust. However, clinical
guidelines are guidelines only. The interpretation and application of
clinical guidelines will remain the responsibility of the individual
clinician. If in doubt contact a senior colleague or expert. Caution is
advised when using guidelines after the review date

Dr Richard Sherman and Dr Thea de Beer 10/ 2011 Review 10/2014

ADULT CRITICAL CARE GUIDELINES FOR SEDATION AND ANALGESIA IN THE

INTUBATED PATIENT
Critical Care Directorate
Nottingham University Hospitals NHS Trust
Introduction
The aims of sedation and analgesia are to facilitate patient acceptance of intubation and
ventilation, to provide relief from anxiety and pain and to decrease oxygen requirements
(Werret, 2003; Murdoch, Cohen, 2000)
The correct management of sedation is one of the most important aspects of Intensive Care
management. Unfortunately it is also one of the most difficult, mainly because patients
cannot communicate easily how they feel and what they need to feel better. Some degree of
sedation (i.e. analgesia hypnosis) is often required to allow patient co-operation with organ
system support and the associated nursing care. An agitated patient has a higher basal
metabolic rate and may reduce the efficiency of supportive care, most commonly ventilation.
While it is clear that leaving a patient agitated and distressed is detrimental to their care this
is equally true of over sedation. All sedative agents share the following problems;
i. accumulation with prolonged infusion, delaying weaning from supportive care increasing
complications and consequently morbidity and mortality
ii. detrimental effects on the circulation leading to increased inotrope requirements
iii. detrimental effects on the pulmonary system - vasculature. increasing VQ mismatch
leading to increased ventilatory support with the consequent increase in complications, and
suppression of cough reflex reducing clearance of pulmonary secretions.
iv. tolerance during sedation and withdrawal when it is stopped
v. no sedative provides rapid eye movement (REM) sleep - i.e. useful sleep. REM sleep
deprivation is thought to be one of the most important causes of ICU psychosis
vi. reduced intestinal motility impairing establishment of enteral feeding and constipation
It is therefore vital that sedation is managed as precisely as possible and given the priority
attention that it deserves.
(ICS Guidelines 2007)
Principles of Management
A drug given by intravenous infusion will take approximately four half-lives to achieve steady
state levels. This means that it will take a significant amount of time for adequate sedation to
be achieved by starting an infusion without a loading dose. It also means that changes in
sedation infusion rate will take some time to be effective.
As a result there is a tendency for infusion rates to be started at a high rate in order to
achieve adequate sedation quickly. Unfortunately, this high initial rate is often continued in
the mistaken belief that it will continue to be needed. This also applies to increases in
infusion rate which tend to be too great.
The correct way to initiate sedation is thus to administer a loading dose which is
titrated to effect and then to start an infusion. Increases in sedative infusion rate
should follow the same principle, i.e. a bolus, titrated to effect, should be administered
and the infusion rate increased by a small increment.

Dr Richard Sherman and Dr Thea de Beer 10/ 2011 Review 10/2014

A commonly used analogy to simplify the understanding of these principles is that of the
leaking bucket. In order to fill the bucket a bolus of water is required. The size of this bolus
is1independent of the size of the leak. However in order to keep the bucket full an infusion
rate which is equal to the size of the leak is required. If the infusion is started with no bolus
then the bucket will never fill.
It is important to remember that combinations of sedatives that act via different mechanisms
are more effective than single agents at high dose. In addition, tolerance to sedatives
develops more quickly at high doses. Alternative sedative agents may need to be
considered.
(ICS Guidelines 2007)
The ideal sedative agent should possess the following qualities:

Both sedative and analgesic

Minimal cardiovascular side effects
Controllable respiratory side effects
Rapid onset/ offset of action
No accumulation in renal/ hepatic dysfunction
Inactive metabolites
Cheap/ cost-effective
Minimal interactions with other drugs

(Werret, 2003)

Choice of Sedative
The choice of sedation in critically ill patients in critical care is determined by several factors
including the patients diagnosis, route and method of ventilation, liver and kidney function
and changes in the patients condition. Propofol and Midazolam are sedative agents that are
widely used within critical care
Propofol
Propofol is a widely used agent for maintenance of sedation in the critically ill. It has a rapid
onset and offset even after prolonged infusion. Propofol has inactive metabolites. It is
however comparatively expensive.
Adverse Effects:
Propofol Infusion Syndrome:
Severe metabolic acidosis, rhabdomyolysis, hyperkalaemia, hypertriglyceridaemia, renal
failure, hepatomegaly and cardiovascular collapse (usually occurs at doses of > 5mg/kg/hr).
Other adverse effects include:
Myoclonic movements and convulsions
Bradycardia
Green urine
Cautions:
Not suitable for patients less than seventeen years of age
Lipid disorders
Egg allergy (egg albumin is a component of Propofol)
Standard Dose:
Induction of anaesthesia by intravenous bolus injection:
1.5-2.5 mg/kg (less in the elderly) at a rate of 20-40 mg every 10 seconds
Sedation in critical care by continuous intravenous infusion 0.3- 4mg/ kg/ hour
Monitor blood-lipid concentration if at risk of fat overload or if sedation used for longer than 3
days. If lipid levels high change to alternative sedation and consider starting lipid lowering
agents.(British National Formulary, 2010)

Dr Richard Sherman and Dr Thea de Beer 10/ 2011 Review 10/2014

Midazolam
Midazolam is a benzodiazepine sedative used in critical care. When given as bolus doses it
has a short elimination half-life (1-4 hours), rapid onset, and short duration of action. Its
active metabolite, alpha-hydroxy-midazolam can accumulate leading to prolonged sedation
in patients following infusion, and especially in patients with a reduced GFR.
Adverse Effects
Gastrointestinal disturbances
Bronchospasm
Ataxia
Involuntary movements
Visual disturbances
Jaundice
Cardiac arrest
Anaphylaxis

Laryngospasm
Respiratory depression and apnoea
Hallucinations
Dysarthria
Increased appetite
Hypotension
Thrombosis

Cautions
Hepatic impairment
Renal impairment
Cardiac disease
Enhanced effects in older person
Vasoconstriction

Pregnancy
Breastfeeding
Respiratory disease
Hypovolaemia

Standard Dose
As an adjunct to induction of anaesthesia by slow intravenous bolus injection
30-300 mcg/kg in steps of 1-2.5 mg every two minutes
Sedation in critical care by continuous intravenous infusion
200 mcg/kg/hour or 1-10 mg/hr
If patient has been exposed to midazolam for more than 7 days do not stop abruptly,
unless there is a good clinical indication.
Decrease dose, or start equivalent doses of
alternative benzodiazepine and wean appropriately.
(British National Formulary, 2010)
Other Sedatives used in ICU
Other sedative agents are used occasionally in ICU, usually under special circumstances.
Clonidine
Clonidine, a centrally acting alpha receptor agonist, is often used to aid weaning from
prolonged opioid sedation, when withdrawal features such as hypertension and tachycardia
may be problematic.
Ketamine
Ketamine is a phencyclidine derivative. It has potent sedative, analgesic and bronchodilator
properties. It is occasionally used in patients with acute severe asthma for its sedative and
bronchodilator activity, and for patients with burn injuries undergoing dressings changes for
its analgesic properties. If used as the sole sedative agent Ketamine frequently leads to
unpleasant dreams/hallucinations. It should therefore only be prescribed in conjunction with a
benzodiazepine (Midazolam) infusion.

Dr Richard Sherman and Dr Thea de Beer 10/ 2011 Review 10/2014

Choice of Analgesia
Opioid analgesics are generally used to provide analgesia for intubated and ventilated
patients as they also provide a degree of sedation. However, some patients in critical care
may not require opioid analgesia examples include some medical patients, and postoperative patients with other forms of analgesia such as an epidural infusion. Morphine,
Fentanyl, Alfentanil and Remifentanil are the most commonly used opioid analgesics within
critical care. As with sedative drugs initial loading of the opioid is needed until patient is
comfortable and then followed by low dose infusion of said opioid.
Morphine

Morphine is a widely used opioid analgesic utilised in critical care. It is metabolised in the
liver to water-soluble renally excreted compounds including morphine-6-glucuronide (M6G)
and morphine-3-glucuronide (M3G). In patients with renal failure accumulation of M6G will
lead to prolonged narcosis. Following bolus dosing the peak effect of morphine is achieved
after 15 minutes and its duration of action is 2-3 hours. Prolonged infusion leads to
accumulation with prolonged narcosis.
Adverse Effects:
As above and:
Histamine Release
Tachycardia
Pulmonary oedema

Hypotension
Tolerance

Standard Dose:
Intravenous bolus injection
2.5-5 mg every 15 minutes
Continuous Intravenous Infusion
1-12 mg/ hr
If patient has been exposed to morphine for more than 7 days do not stop abruptly, unless
there is a good clinical indication. Decrease dose, or start equivalent doses of alternative
opioids and wean appropriately.
(British National Formulary, 2010)
Alfentanil
Alfentanil has a short duration of action and a rapid, predictable recovery even following
infusion. It is hepatically metabolised to inactive substances and has a small volume of
distribution. It is useful in patients with renal failure, but may accumulate in patients with liver
failure. It is comparatively expensive.
Adverse Effects
Respiratory depression and apnoea
Hypotension
Constipation
Delayed gastric emptying

Bradycardia
Nausea and vomiting
Biliary spasm
Chest wall rigidity

Standard Dose
Induction of anaesthesia by intravenous bolus injection
50 - 100mcg/kg bolus
Maintenance of anaesthesia by continuous intravenous infusion 0.5-10 mg/hr (up to
1mcg/kg/min)
(British National Formulary, 2010)
1

Dr Richard Sherman and Dr Thea de Beer 10/ 2011 Review 10/2014

Fentanyl
Following IV bolus injection Fentanyl has rapid onset of action, with short/medium duration of
approximately 1020 minutes. But following a prolonged infusion it becomes a long-acting
drug, with a greater half-life than that of morphine. It is the most cardio-stable opioid. In
critical care settings it is usually given as a bolus - at induction of anaesthesia, or as
analgesia for short surgical procedures. It is comparatively expensive.
Remifentanil
This is an ultra-short acting opioid with a half-life of only three minutes even after prolonged
infusion. It is metabolised by non-specific blood/tissue esterases and does not accumulate
even in severe renal or liver failure. It has potent analgesic and respiratory depressant
properties. Remifentanil should only be prescribed by a Consultant Intensivist. Expensive.
Sedation Choice
Choice of sedation should be determined by the sedation algorithm (Appendix 1).
Assessment of Sedation Level
The ideal level of sedation is to keep the patient comfortable and lightly asleep but easily
aroused.
Certain patients (e.g. head injuries) may need a higher level of sedation including the use of
paralysing drugs whereas minimal or no sedation may be used in patients being ventilated
via a tracheostomy.
The level of sedation should be monitored, chartered hourly, and the choice of drug, the dose
and route of administration adjusted appropriately.
There is a risk of over-sedation in critical care, when infusions of drugs are used and not
adjusted according to the level of sedation of the patient. Over-sedation may cause problems
such as coma, respiratory depression, hypotension, bradycardia, gastrointestinal stasis,
immunosuppression and renal failure in addition to the adverse side effects of the drugs
themselves (Werret, 2003). Over-sedation also leads to delayed weaning from ventilatory
support.
The Richmond Agitation Sedation Scale is the score of choice used to assess sedation levels
in NUH critical care areas. (See Appendix 2).
Sedation and analgesia infusions should be adjusted in accordance with the sedation
guidelines (See Appendix 2).
Pain Assessment
As with sedation, there are pain-scoring scales adaptable for local use. There is difficulty of
adequate pain assessment in the sedated and ventilated patient; however, if optimum
sedation is maintained, a pain score in conjunction with sedation assessment may be
established. The number analogue scale is the tool of choice within Critical Care Directorate,
Nottingham University Hospitals NHS Trust (See Appendix 3).

Dr Richard Sherman and Dr Thea de Beer 10/ 2011 Review 10/2014

Daily Sedation Holds Guidelines

Critical Care Directorate
Nottingham University Hospitals NHS Trust
Introduction
Administration of sedatives by continuous infusion may prolong the duration of mechanical
ventilation and the length of stay in critical care (Kress et al, 2000; Kollef et al, 1998).
Performing daily sedation holds on patients receiving a continuous infusion of sedative
agents has been shown to prevent over sedation, reduce the amount of time spent on
mechanical ventilation and reduce time spent in critical care (Kress et al, 2000; Kollef et al,
1998).
Indications
Patients who are being mechanically ventilated and who are receiving a continuous
sedation infusion.
Contra-indications
Patients receiving neuromuscular blocking agents
Traumatic brain injury patients with raised intra cranial pressure
Patients requiring FiO2 60% , or PEEP > 10 cmH20 or, inverse ratio or,
prone ventilation
Patients with uncleared spines, until discussion with medical team.
Haemodynamically unstable patients.
Locally acting chemotherapy drugs that require immobilisation of patient
No airway trained personnel immediately available on the unit.
Patients receiving compassionate care
Procedure for Sedation Holds
The need for daily sedation hold should be assessed by Critical Care Consultant on the
morning ward round and documented on the daily review sheet
If recommended by the Critical Care Consultant, the bedside nurse should perform the
daily sedation hold at a convenient time in the morning, as described below:
1.

Sedation infusion should be discontinued

2.

When the patient can follow commands or becomes agitated (sedation score +2 or
above) bolus should be given and the sedation infusion should be recommenced at
half the original infusion rate. (See Appendix 2)

3.

Sedation infusion should then be adjusted until optimal level of sedation is achieved
using the guidelines in appendix 2

Dr Richard Sherman and Dr Thea de Beer 10/ 2011 Review 10/2014

Appendix 1

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Patients receiving neuromuscular blocking agents

Traumatic brain injury patients with raised intra cranial pressure
Patients requiring FiO2 ! 60% , or PEEP > 10 cmH20 or, inverse ratio or, prone
ventilation
Patients with uncleared spines, until discussion with medical team.
Haemodynamically unstable patients.
Locally acting chemotherapy drugs that require immobilisation of patient
No airway trained personnel immediately available&
Patients receiving compassionate care&

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Dr Richard Sherman and Dr Thea de Beer 10/ 2011 Review 10/2014

Appendix 2:

Richmond Agitation Sedation Scale

Critical Care Directorate
Nottingham University Hospitals NHS Trust

Introduction
The patients sedation score should be assessed hourly and evaluations documented on the
patients observation chart.
If patient is receiving neuromuscular blocking agents please insert P
If patient is sleeping please insert S
Richmond Agitation Sedation Scale (RASS) * and Management
Reassess patient prior and following each bolus dose or infusion rate change.

Score Term

Description

Action
Bolus 2ml sedative agent
every 2 minutes until a
score of +1 achieved

+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 movements not aggressive

vigorous.

0
-1

-2

Light sedation

Not fully alert, but has

sustained awakening
(eye-opening/eye contact)
to voice (>10 seconds)
Briefly awakens with eye
contact to voice (<10 secs)

-3

Moderate sedation Movement or eye opening

to voice (no eye contact)

-4

Deep sedation

No response to voice, but

movement or eye opening to
physical stimulation

-5

Unrousable

No response to voice or
physical stimulation

Bolus 1ml sedative agent

every 2 minutes until a
score of +1 achieved
Increase infusion by 1ml/hr
Maintain sedative infusion
at current rate for maximum
of 6 hours

Alert and calm

Drowsy

Increase infusion by 2ml/hr

Verbal
Stimulation

After 6 hours reduce

infusion rate by 1ml/hr

Reduce sedative infusion

rate by 1ml/hr

Discontinue sedative
infusion unless contraPhysical
indicated
Stimulation
e.g. paralysed, head injury,
terminal care

Procedure for RASS Assessment

1. Observe patient
a. Patient is alert, restless, or agitated.
(score 0 to +4)
2. If not alert, state patients name and say to open eyes and look at speaker.
b. Patient awakens with sustained eye opening and eye contact.
(score 1)
c. Patient awakens with eye opening and eye contact, but not sustained.
(score 2)
d. Patient has any movement in response to voice but no eye contact.
(score 3)
3. When no response to verbal stimulation, physically stimulate patient by shaking shoulder
and/or rubbing sternum.2
e. Patient has any movement to physical stimulation.
(score 4)
f. Patient has no response to any stimulation.
(score 5)
* Sessler CN. et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care patients.
Am J Respir Crit Care Med 2002;166:1338-1344.* Ely EW. et al. Monitoring sedation status over time in ICU patients: the
reliability and validity of the Richmond Agitation Sedation Scale (RASS). JAMA 2003; 289:2983-2991.

Dr Richard Sherman and Dr Thea de Beer 10/ 2011 Review 10/2014

Appendix 3:

Pain Assessment Scale

Critical Care Directorate
Nottingham University Hospitals NHS Trust

Introduction
Pain assessment score should be assessed hourly
Reassess patient prior and following each bolus dose or infusion rate change.
This is for ventilated patients only.
Pain Score
0

Patient Characteristics
Pain free

Action
If pain free for six hours consider
reducing analgesia infusion by
1ml/hr

Mild pain

Deliver 1ml bolus of analgesia

every 2 minutes until pain free

Moderate pain

Deliver 2ml bolus of analgesia

every 2 minutes until pain free
Increase analgesia infusion by
1ml/hr

Severe pain

Deliver 3ml bolus of analgesia

every 2 minutes until pain free
Increase analgesia infusion by
1ml/hr

Dr Richard Sherman and Dr Thea de Beer 10/ 2011 Review 10/2014

Appendix 4 - EQUALITY IMPACT ASSESSMENT

1. Name of Policy or Service
Adult critical care guideline for sedation and analgesia in intubated patients.
2. Name of Responsible Manager
Dr D Selwyn
3. Name of person completing assessment
Dr T de Beer
4. Date EIA Completed
4 November 2011
5. Description and Aims of Policy/Service (including relevance to equalities)
The purpose of this policy is supply guidance for choice of sedative and analgesic as well as
guidance on discontinuation.
8. Results of Initial Screening or Full Equality Impact Assessment:
Equality Group
Age
Gender
Race
Sexual Orientation
Religion or belief
Disability
Dignity and Human Rights
Working Patterns
Social Deprivation

Assessment of Impact
NO RELEVANCE
NO RELEVANCE
NO RELEVANCE
NO RELEVANCE
NO RELEVANCE
NO RELEVANCE
NO RELEVANCE
NO RELEVANCE
NO RELEVANCE

9. Decisions and/or Recommendations (including supporting rationale)

This guideline is a guide to rationalise sedation and analgesia in the intubated critically ill
patient. It aims to improve choice of agents to initiate sedation and facilitate analgesia. Based
on guidelines from the ICS and BNF.
10.

Equality Action Plan (if required)

N/A

11.

Monitoring and Review Arrangements (including date of next full review)

It is recommended that this policy and EIA be reviewed annually in order to assess its
functionality.

Dr Richard Sherman and Dr Thea de Beer 10/ 2011 Review 10/2014


Screening Grid

Equality Area
(Protected
Characteristics)

Is this policy or
service RELEVANT
to this equality
area?
YES / NO

Age
Disability
Gender
Reassignment
Race
Religion or Belief
Sex
Sexual Orientation
Marriage & Civil
Partnership
Pregnancy &
Maternity
Social Deprivation
Dignity and Human
Rights
Working Patterns

NO
NO

Assessment of Potential
Impact:
HIGH
MEDIUM
LOW
NOT KNOWN
positive (+)
negative (-)
LOW
LOW
LOW
LOW

NO

LOW

LOW

NO
NO
NO
NO

LOW
LOW
LOW
LOW

LOW
LOW
LOW
LOW

NO

LOW

LOW

NO

LOW

LOW

NO

LOW

LOW

NO

LOW

LOW

NO

LOW

LOW

Dr Richard Sherman and Dr Thea de Beer 10/ 2011 Review 10/2014