Southern African Journal of Anaesthesia and Analgesia

ISSN: 2220-1181 (Print) 2220-1173 (Online) Journal homepage: https://www.tandfonline.com/loi/ojaa20

Sedation in the ICU

AM Travers

To cite this article: AM Travers (2010) Sedation in the ICU, Southern African Journal of
Anaesthesia and Analgesia, 16:1, 96-100, DOI: 10.1080/22201173.2010.10872647

To link to this article: https://doi.org/10.1080/22201173.2010.10872647

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Published online: 12 Aug 2014.

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 Refresher Course: Sedation in the ICU
Sedation in the ICU
Introduction
The ICU is a hostile environment, and while pain is often the root cause
of distress experienced by the patient in the unit, anxiety, dyspnoea,
delirium and sleep deprivation may be additive or synergistic.1,2 Factors
that provoke these components of distress include underlying medical
conditions, acute medical/surgical illness, and “routine” critical care
practices like mechanical ventilation, the presence of indwelling tubes
and catheters, iatrogenic illness, medication side effects, turning and
suctioning, and excessive noise and light in the ICU.3
With pain being central to ICU discomfort, current sedation strategies
are based on providing analgesia first, and adding sedation as required
(“analgo-sedation”). Sedation needs vary widely and are influenced by
many pharmacokinetic and pharmacodynamic variables in this group of
patients. Therefore, all sedation techniques must be patient-focused and
individualised to patient needs. This goal directed approach improves
patient outcome and reduces the use of sedative drugs.4
Aims of analgo-sedation
ICU sedation is aimed at keeping the patient comfortable but easily
rousable.5 Deep sedation with or without muscle relaxants is rarely
indicated,and is associated with a higher incidence of delirium and
death.6,7 Analgo-sedation is administered to relieve pain, anxiety
and discomfort, and to facilitate treatment and nursing.4 Effective
patient-focused sedation strategies encompass targeted analgo-
sedation using both pharmacological and non-pharmacological
methods, and sedation scoring parameters to direct the level of
sedation. These strategies must also include methods that strive to
maintain sleep cycles and allow for daily awakening from sedation.
Early recognition and treatment of delirium is of cardinal importance,
as delirium is associated with higher ICU morbidity and mortality.8
Evaluation of pain, sedation and delirium
Sedation scales and pain evaluation instruments are important in
patient-focused therapy, establishing a target level of sedation and
ensuring that pain is addressed and treated adequately.
Pain evaluation
In patients who are able to report their level of pain by speaking,
pointing or nodding, the 10 cm visual analogue scale is relatively
S Afr J Anaesthesiol Analg
Travers AM
Private practice and part-time consultant, UFS
Correspondence to: Anthony Travers, e-mail: travers@webafrica.org.za
easy to use. Variations of this scale include a scale with extremes of
measurement anchored by numerical (1 – 10), descriptive (“no pain”
to “worst pain ever”), or diagrammatic (smiling face to crying face)
variables.9
In patients who are unable to indicate their pain, pain levels are
inferred by observing patient behaviour. The Behaviour Pain Scale
(BPS) is based on a sum score of three parameters: facial expression,
movements of upper limbs, and compliance with mechanical
ventilation. Each parameter is scored from 1 (no response) to 4 (full
response), with a maximum score of 12.10
The Adult Numerical Pain Scale evaluates five parameters: face,
activity, guarding, physiologic I (vital signs), and physiologic II (skin
and pupils).11 The Critical care Pain Observation Tool (CPOT) has four
components: facial expression, body movements, muscle tension
and compliance with ventilator/vocalisation.12 Current recommended
practices include a combination of a numeric pain scale and either
the BPS or CPOT.13
Evaluation of sedation
The Ramsay Sedation Scale has been used for the past three
decades as a tool to evaluate sedation in the ICU (Table I).14
Sedation should be targeted to a Ramsay score of 2 to 3. Other
sedation scales that have evolved are the Sedation-Agitation
Scale (SAS), the Motor Activity Assessment Scale (MAAS), the
Vancouver Interactive and Calmness Scale (VICS), the Richmond
Agitation Sedation Scale (RASS), the Adaptation to Intensive Care
Environment (ATICE), and the Minnesota Sedation Assessment
Tool (MSAT).15-20
Table I: The Ramsay Sedation Scale (RSS)
Awake levels Asleep levels
1 Anxious, agitated or restless 4 Brisk response to light glabella
tap or loud auditory stimulus
2 Cooperative, orientated and 5 Sluggish response to light
tranquil glabella tap or loud auditory
stimulus
3 Responds to commands only 6 No response to light glabella tap
or loud auditory stimulus
All these scales share common evaluated parameters. The first
parameter is consciousness, usually ranging from alert to comatose,
96 2010;16(1)
 Refresher Course: Sedation in the ICU

with subdivisions of arousal or awakeness, often in response to but they may be of use in the patient receiving muscle relaxants or
stimuli of increasing intensity (RSS, RASS, ATICE, MSAT). Higher levels paralysed by disease, where inadequate sedation may be detrimental.
of consciousness are tested by noting cognition or comprehension
(RASS, ATICE). The second parameter measured using these scales
Drugs used for analgesia and sedation in the ICU
is agitation or, conversely, calmness. Identification of agitation
facilitates prompt therapeutic intervention and treatment of factors
The move away from deep sedation to analgo-sedation has led to a
that may cause the agitation, such as pain, delirium, a malpositioned
endotracheal tube or myocardial ischaemia.21 reduction in the use of hypnotic drugs.26

Objective measurement of cerebral function Analgesia

Cortical activity monitors record cortical EEG signals and analyse
the frequency and power to determine the status of the patient.
Fast Fourier transformation allows a power vs. frequency histogram
to be displayed as a spectral array. Various forms of this concept
have been developed commercially, including Bispectral Index (BIS)
monitoring, Patient State Index (PSI), Central State monitor, and the
Narcotrend Monitor.22-25
None of these monitors has been adequately proven in the ICU,
Analgesia should be titrated according to individual patient needs,
consisting of a basal regimen accounting for elements like pain
perception, age and body mass in combination with rescue dosing
for incidental and procedural pain. Parenteral administration is the
preferred route, as enteral and transcutaneous absorption may be
unpredictable in the ICU patient. Epidural administration of local
anaesthetics and opioids can also provide effective analgesia.
Opioids form the mainstay of analgesia in the ICU. Morphine, fentanyl
and remifentanil are used most widely.

Morphine

The hydrophilic opioid, morphine, has been used as an analgesic for 200 years.

ONSET/OFFSET OF ACTION METABOLISM/ELIMINATION DOSE SIDE EFFECTS

Onset 15 – 20 min Hepatic metabolism Loading dose Respiratory depression

- 80% morphine-3-glucuronide 1 – 1,5 mg iv every 5 min
Offset 30 min – 8 h with no analgesia Maximum 0,5mg/kg Histamine release with hypotension
- 20% morphine-6-glucuronide
Dependent on organ function and with potent analgesia Maintenance
duration of infusion 2 – 4 mg/h
Both metabolites accumulate with Infusions lead to prolonged
renal dysfunction. elimination half-life.

Fentanyl

Fentanyl and sufentanil are fat soluble opioids with large volume of distribution and the risk of accumulation and delayed recovery with prolonged
administration.

ONSET/OFFSET OF ACTION METABOLISM/ELIMINATION DOSE SIDE EFFECTS

Onset 2 – 5 min Hepatic metabolism to non-active Loading dose Respiratory depression

Offset unpredictable due to
prolonged context sensitive half-
life with continuous infusion
metabolites 0,5 - 1 µg/kg iv every 5 min
Maximum 2 µg/kg
Accumulation due to organ-dependent
metabolism Infusion
5 – 10 µg/kg/h titrated at
1 – 2 µg/kg/h increments

Remifentanil

Mean duration of mechanical ventilation is reduced when a remifentanil-based regimen is used, as opposed to a morphine-based regimen or
midazolam-morphine/fentanyl-based regimen.27,28

ONSET/OFFSET OF ACTION METABOLISM/ELIMINATION DOSE SIDE EFFECTS

Onset 1 min Metabolised by non-specific esterase in plasma, red Starting infusion Respiratory depression
blood cells and interstitial tissue 6 – 9 µg/kg/h
Offset 10 min, regardless of infusion duration Hypotension
Titrate 1,5 µg/kg/h
Half-life about 3 min even after 8 h infusion

S Afr J Anaesthesiol Analg 97 2010;16(1)

 Refresher Course: Sedation in the ICU

Analgo-sedation

Both ketamine and dexmedetomidine possess analgesic and sedative properties.

Ketamine

Ketamine is an NMDA-receptor antagonist with centrally mediated sedation and amnesia, and spinally mediated analgesia. The drug facilitates
endogenous catecholamine release, thereby countering hypotensive effects. A benzodiazepine should be co-administered to prevent neuropsychiatric
side-effects, although this seldom occurs with low doses used for sedation.

ONSET/OFFSET OF ACTION METABOLISM/ELIMINATION DOSE SIDE EFFECTS

Onset 1 min
Offset dependent on dose and
duration of administration
Elimination half-life 2,5 - 3,5 h
Metabolised in liver to norketamine Loading dose Neuropsychiatric effects seldom a
0,1 - 0,2 mg/kg every 10 min to problem at low doses
Excreted in urine and bile maximum 0,5 mg/kg
Maintenance
0,5 – 1 mg/kg/h

Dexmedetomidine

Dexmedetomidine is a centrally acting α2-agonist with sedative and analgesic properties. Patients are highly rousable and cognitive function is
well maintained. Dexmedetomidine has an opioid-sparing effect.

ONSET/OFFSET OF ACTION METABOLISM/ELIMINATION DOSE SIDE EFFECTS

Onset anxiolytic and analgesic
effects almost immediate,
sedation within 20 min
Offset about 2 h after 1 µg/kg,
after infusion about 2 – 3 h
Complete biotransformation in liver Loading dose Biphasic cardiovascular effect:
1 µg/kg over 10 min transient hypertension and
bradycardia with loading dose;
Maintenance hypotension and bradycardia is then
0,05 - 0,7 µg/kg/h seen, especially in hypovolaemic
patients

Sedation

Sedative-hypnotic drugs interact with different components of the ϒ-amino butyric acid (GABA) receptor. These drugs cause sedation, anxiolysis
and amnesia, but have no analgesic properties. They may accumulate with liver and renal dysfunction, and with prolonged administration.

Midazolam

ONSET/OFFSET OF ACTION METABOLISM/ELIMINATION DOSE SIDE EFFECTS

Onset 2 - 3 min
Offset: short acting, but
accumulation with infusion
Liver oxidation via CYP450; metabolism Bolus dose Respiratory depression at high
impeded by other drugs metabolised by 1 – 5 mg doses, or in combination with
CYP450 (0,03 mg/kg/h) opioids.
Active metabolite Continuous infusion not
1-hydroxymethylmidazolam. recommended; increase in
context sensitive half-life
Extensive protein binding

Lorazepam

ONSET/OFFSET OF ACTION METABOLISM/ELIMINATION DOSE SIDE EFFECTS

Onset 30 min Liver glucuronidation to inactive metabolites Bolus dose Independent risk factor for developing
2 – 4 mg every 2 - 4 h delirium
Offest: intermediate duration of
action Propylene glycol accumulation with
prolonged use leading to metabolic acidosis
and hyperosmolality

S Afr J Anaesthesiol Analg 98 2010;16(1)

 Refresher Course: Sedation in the ICU

Propofol
Propofol is a lipophilic GABA-receptor agonist which crosses the
blood-brain barrier rapidly. The offset of action is a function of the
depth of sedation, duration of infusion and patient size and body
composition.29 The emergence time for light sedation up to 3 days
is rapid (< 35 min). For sedation up to 14 days, emergence time
is about 3,5 hours. For deep sedation, emergence time is 25 hours
after a 24 hour infusion, and 3 days for infusion lasting 7 – 14 days.
Propofol sedation allows for more rapid extubation than midazolam,
without influencing ICU discharge time.30 Propofol infusion syndrome
is a rare but potentially fatal side effect observed when infusion rates
> 5 ml/kg/h for more than 48 hours.31 Concomitant use of steroids
and catecholamines are also predisposing factors to the syndrome.

ONSET/OFFSET OF ACTION METABOLISM/ELIMINATION DOSE SIDE EFFECTS

Onset rapid < 1 min Conjugation in liver to inactive metabolites 0,5 - 3 mg/kg/h Hypotension and respiratory depression in
Offset rapid, but increases with cardiomyopathy, sepsis, elderly patients and
deep/prolonged sedation with concurrent opioids use

Hyperlipidaemia

Increased risk of infection

Metabolic acidosis in children

Propofol infusion syndrome

Volatile sedation Figure 1: Guide to sedation in the ICU (Mer M, Levy B)

Although not licensed for sedation in the ICU,

volatile anaesthetic agents hold promise as
a viable alternative to intravenous drugs.
Technical devices connected between the
patient and the ICU ventilator have simplified
the ease of administration of these drugs in
the ICU setting.32 Isoflurane administered
via this device has been shown to be safe
and effective, with shorter awakening times
when compared with midazolam.33

Conclusion

Effective analgo-sedation is essential in the

management of mechanically ventilated
patients. Structured assessment tools for
both pain and level of sedation and guidelines
for drug administration are essential to
optimise therapy and limit side effects.
The aim should be to treat pain first and
to minimise sedation, thereby maintaining
patient comfort and patient-examiner
interaction, while improving outcome.

References
1. Chanques G, Jaber S, Barbatte E, et al. Impact of systematic evaluation of pain and agitation in an
intensive care unit. Crit Care Med 2006,34:1691–9.
2. Novaes MA, Knobel E, Bark AM, et al. Stressors in ICU: perception of the patient, relatives and health
care team. Intensive Care Med 1999;25:1421–6.
3. Sessler CN, Grap MJ, Brophy GM. Multidisciplinary management of sedation and analgesia in
critical care. Semin Repir Crit Care Med 2001;22:211–25.
4. Mer M, Levy B. Sedation in ICU: Best Practice Guidelines. Nesibopho Healthcare 2009.
5. Sessler CN, Varney K. Patient - focused sedation and analgesia in the ICU. Chest 2008;133:552–65.
6. Lerch C, Park BGR. Sedation and analgesia. British Medical Bulletin 1995;55(1):76–95.
7. Fraser GL, Riker RR. Sedation and analgesia in the critically ill adult. Curr Opin Anaesth
2007;20(2):119–23.
8. Pun BT, Ely EW. The importance of diagnosing and managing ICU delirium. Chest 2007;132:624-36.
9. Sanders KD, McArdle P, Lang JD. Pain in the intensive care unit: recognition, measurement,
management. Semin Respir Crit Care Med 2001;22:127–36.
10. Payen JF, Bru O, Bosson JL, et al. Assessing pain in critically ill sedated patients by using a
behavioural pain scale. Crit Care Med 2001;29: 2258–63.
11. Odhner M, Wegman D, Freeland N, et al. Assessing pain control in nonverbal critically ill adults.

S Afr J Anaesthesiol Analg 99 2010;16(1)

 Refresher Course: Sedation in the ICU

Dimens Crit Care News 2003;22:260–7.

12. Gelineas C, Fillion L, Puntillo FA, et al. Validation of the critical care pain observation tool in adult
patients. Am J Crit Care 2006;15:420–7.
13. Jacobi J, Fraser GL, Coursin DB, et al. Clinical practice guidelines for the sustained use of sedatives
and analgesics in the critically ill adult. Crit Care Med 2002,30:119–41.
14. Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxalone-
alphadolone. BMJ 1974;2:656–9.
15. Riker RR, Picard JT, Fraser GL. Prospective evaluation of the sedation-agitation scale for adult
critically ill patients. Crit Care Med 1999;27:1325–9.
16. Devlin JW, Baleski G, Mlynarck M, et al. Motor activity assessment scale: a valid and reliable
sedation scale for use with mechanically ventilated patients in an adult surgical intensive care unit.
Crit Care Med 1999;27:1271–5.
17. De Lemas J, Tweeddale M, Chittack D. Measuring quality of sedation in adult mechanically
ventilated critically ill patients; the Vancouver interaction and calmness scale. Sedation focus group.
J Clin Epidem 2000;53:908–19.
18. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation Sedation Scale: validity and
reliability in adult intensive care unit patients. Am J Resp Crit Care Med 2002;166:1338-44.
19. De Jonghe B, Cook D, Griffith L. Adaptation to the Intensive Care environment (ATICE): development
and validation of a new sedation assessment instrument Crit Care Med 2003;31:2344–54.
20. Weinent C, McFarland L. The state of intubated ICU patients. Development of a two-dimensional
sedation rating scale for critically ill adults. Chest 2004;126:1883–90.
21. Sessler CN, Grop MJ, Ramsay MA. Evaluating and monitoring analgesia and sedation in the intensive
care unit. Crit Care 2008;12(3):S2.
22. Myles PS, Leslie K, McNeil J, et al. Bispecral index monitoring to prevent awareness during
anaesthesia: the B-aware randomised control trial . Lancet 2004;363:1757– 63.
23. Draver D, Ortega HR. Patient State Index. Best Pract Res Clin Anaesthesia 2006;20:121–8.
24. Corinez LI, Delfino AF, Fuentes R, Muraz HR. Performance of the Cerebral State index during
increasing loads of propofol anaesthesia: a comparison with the Bispectral Index. Anesth Anal
2007;104:605–10.
25. Kreuer S, Wilhelm W, Grundman U, et al. Narcotrend index vs. Bispectral index as
electroencephalogram measures of anesthetic drug effect during propofol anaesthesia. Anaesth
Anal 2004;98:692–7.
26. Park G, Lane M, Rogers S, Basset P. A comparison of hypnotic and analgesic based sedation in a
general intensive care unit. BJA 2007;98:76–82.
27. Dahaba AA, Grabner T, Rehak PH, et al. Remifentanil versus morphine analgesia and sedation for
mechanically ventilated critically ill patients: a randomized double blind study. Anesthesiology
2004;101:640–6.
28. Breen D, Karabinis A, Malbrain M, et al. Decreased duration of mechanical ventilation when
comparing analgesia-based sedation using remifentanil with standard hypnotic-based sedation for
up to 0 days in intensive care unit patients: a randomized trial. Crit Care 2005;9:R200.
29. Barr J, Egon TD, Sandaval NF, et al. Propofol dosing regimens for ICU sedation based on an
integrated pharmacokinetic-pharmacodynamic model. Anaesthesia 2001;95:324–33.
30. Kall RI, Sandham D, Cardinal P, et al. Propofol vs. midazolam for ICU sedation: a Canadian multicentre
randomized trial. ºChest 2001;119:1151–9.
31. Wappler F. The propofol infusion syndrome (in German). Deutshches Arzteblatt 2006;11:A705–10.
32. Benton J, Sargentini C, Nguygen JL, et al. AnaConDa reflection filter: bench and patient evaluation of
safety and volatile anaesthetic conservation. Anesth analg 2007;104:130–4.
33. Sackey PV, Mortling GR, Granath F, Rodel PJ. Prolonged isoflurane sedation of intensive care unit
patients with anesthetic conserving device. Crit Care Med 2004;32:2241–6.

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