The UK Society for Intravenous Anaesthesia
Based in the UK - as a resource for Anaesthesia Worldwide

Oxford Meeting - November 2002

Opioids in the ICU

Dr Atul Kapila, Royal Berkshire Hospital, Reading, Berkshire

 "When launched here in the United Kingdom in 1996 Remifentanil promised much. 'A Truly Predictable Opioid?' was how Carl Rosow 1 had phrased it and indeed it was. A designer drug developed in the laboratories of Glaxo (as it was then) in the Research Triangle of North Carolina - it was to change how opioids were used in anaesthesia.

 Remifentanil's unique characteristic is its metabolism. A phenylpiperidine derivative and related to the other synthetic opioids fentanyl, alfentanil and sufentanil; remifentanil was given an ester linkage at position 1 of the piperidine ring. Cleavage by blood and tissue esterases gives rise to metabolites that have nearly no activity at the mu-receptor. Remifentanil also has small volumes of distribution. The combination of rapid clearance and a small volume of distribution produces a drug with a uniquely evanescent effect.

To summarize the pharmacokinetic and pharmacodynamic differences between rem ifentan i and the presently available opioids:

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the drug is cleared extremely rapidly from the plasma

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the plasma-effect site equilibration is very rapid

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the rate of decline in plasma and effect-site remifentanil concentration will be nearly independent of the infusion duration

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a remifentanil infusion rate will rapidly approach steady-state in the plasma and effect site

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the relationship between infusion rate and opioid concentration will be less variable for remifentanil than for other available opioids" 

I wrote the above for the Belfast, SIVA 2000 meeting and I have reproduced it here as background for my discussion on opioids in ICU as remifentanil gained a licence for ICU use in March of this year.

Will remifentanil fulfil the promise of its unique pharmacology? It's probably too early to say its place in our anaesthetic repertoire is still developing. 

If we briefly look at the use of opioids in the ICU in general there seem to be broad themes in how they are viewed:

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Sedation and Analgesia (the latter being still all too often neglected)

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Specialty uses - cardiac and neuro

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Special procedure uses - percutaneous tracheostomy or bronchoscopy for example

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Routes of administration

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Evidence of benefit - outcomes such as mortality and resource utilisation

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Evidence of harm - delayed wakening, withdrawal syndromes, post-traumatic stress syndromes or effects on body systems - cardiac and neuro for example

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Pharmacological - drug interactions, tolerance, activity of metabolites and clearance

How does remifentanil compare with our standard intravenous opioids - morphine, fentanyl and alfentanil? Can we predict where some of the problems may lie?

 References:  

1. Remifentanil. Cohen C, Royston D. Current Opinion in Critical Care 2001 ;7:227-231

2. Sedative and analgesic practice in the ICU: The results of a European Survey. Soliman HM, Melot C, Vincent JL. Brit Journal of Anaesth 2001 ;87:186-192

3. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Judith Jacobi et al. Critical Care Medicine 2002;30:119-141

4. Lower requirement for sedation with a remifentanil-based analgesia/sedation technique in ICU patients. Breen DP et al. Int Care Med 2002; 28(S1):A701, S180

 

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