"improving intensive care in Scotland"

Sedation and Analgesia in ICU


  • Opioids are defined as drugs which act on opioid receptors.

  • The 3 main classes of opioid receptors are Mu, Kappa and Delta with the desired therapeutic effects being principally through Mu receptor agonism.

  • A wide range of opioids (e.g. morphine, alfentanil, remifentanil, fentanyl) are used in ICU, but morphine and alfentanil predominate.

  • Morphine is an agonist on all 3 receptors whereas fentanyl/alfentanil/remifentanil can be regarded as pure Mu-receptor agonists.

  • Opioids do not provide amnesia or reduce the awareness of stressful events, so therefore need supplemented with a sedative agent where required.

  • Side effects/complications with all of the above opioids include:

    • Respiratory depression with a characteristic slow respiratory rate but normal tidal volume (particular caution with actual/suspected raised intracranial pressure and spontaneous ventilation).

    • Laryngeal reflex suppression with impaired cough.

    • Hypotension via sympatholysis (and therefore caution in high sympathetic tone states) and vagally mediated bradycardia.

    • Gastrointestinal tract hypomotility/ileus with constipation, nausea and vomiting and inadequate enteral nutrition.

    • Sedation, meiosis, poor quality sleep, euphoria/dysphoria, toxicity (hallucinations, nightmares).

    • Tolerance, dependence and opioid withdrawal syndrome.

  • Alfentanil, fentanyl and remifentanil cause minimal histamine release and are preferred in asthma/allergy.

  • The shorter acting alfentanil, remifentanil and fentanyl may be advantageous for likely short ICU stays, but your prescribing practice should follow your own ICUs guidelines/practices.



  • Morphine intravenously is made up as 1mg/ml solution administered by continuous infusion (range 0.5-5mg/hr) or intermittent bolus (approximately 1-5mg) with titration to effect. PCAs can be used in cooperative patients.

  • Intravenously it has a peak effect at 15-30 minutes and a duration of action in healthy adults of 2-4 hours. However, morphine's duration of action is frequently prolonged in critical illness.

  • Morphine causes histamine release and therefore should be used cautiously in asthmatics/bronchospasm and cardiovascularly unstable patients.

  • It is metabolised in the liver to active metabolites which accumulate with prolonged infusion.

    Morphine's metabolites are excreted predominately in the urine. Their reduced clearance in those with renal failure necessitates either reduced dosing or avoidance of morphine in these patients.



  • Is made up as 0.5 or 1mg/ml solution and usually runs as an intravenous infusion at 0.5-5mg/hr.
  • It has a peak effect at 90 seconds and a duration of action after a single bolus of 5-10 minutes.

  • Its clearance from the plasma is largely through hepatic metabolism providing a relatively stable duration of action when administered by infusion (context sensitive half time 50-55 minutes), though this may be prolonged in critical illness.

  • Renal failure has minimal effect on its clearance, thus making it an appropriate choice in these patients



  • Is only administered as a continuous intravenous infusion and is made up in a variety of strengths (1/2/5mg diluted into 40 or 50mls of saline).

  • It acts within 1-3 minutes and has a very stable and short duration of action (context-sensitive half time 3-8mins).

  • It is metabolised by plasma esterases and is therefore unaffected by hepatic and renal failure. It does not accumulate to any significant extent.

  • Great care must be used with its infusion because discontinuation will result in the rapid removal of all its analgesic effect.

  • Infusion doses are either 0.02-0.2mcg/kg/min (with 5 min titrations of 0.025mg/kg/min) or using a target controlled infusion (TCI) of 0.5-5ng/ml.


  • Fentanyl is not commonly used for analgesia in the ICU because it accumulates with infusions and thus generally requires intermittent intravenous administration, which is inconvenient.

  • Its dose is approximately 0.3-1.5mcg/kg every 30-60 mins when given intermittently and 0.7-10mcg/kg/hr when given by continuous infusion.

  • Intravenously it has a peak effect at approximately 5 minutes with a duration of action after a single bolus of 30-60 minutes.

  • Continuous infusions if used should be limited to short durations (hours) because it becomes very long acting (i.e. has a very long, variable context-sensitive half-time) with more prolonged infusions.

  • Fentanyl is extensively metabolised in the liver to essentially inactive metabolites which are predominately excreted in bile. It can therefore be used in renal failure, with the above guidance.

  • Transdermal patches can be used but only in haemodynamically stable patients, and usually with more chronic, stable analgesic requirements.

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