Inadequate Sedation All ICU patients suffer from severe sleep deprivation. REM sleep is 6% ( Normal 25 %). Stress neuroendocrine response ( ACTH, GH, Aldosterone, Adrenaline,.....) Release of cytokines inflammatory response.
Choice of the sedative drug Short-term Vs long-term sedation. Pain & painful Procedures. Organ problems (Renal, hepatic, brain, CVS). Drug withdrawal (Alcohol, heroin,.....) Prescriber & Prescription.
Which Medication? Soliman et al, Brit J Anaesth 2001;87:186-92
IV Anaesthetics; Thiopentone Acts on the GABA A. Zero order kinetics (accumulation). Provides a cerebral protection effect. Main uses in ICU: - High ICP. - Status epilepticus
Opioids; Morphine Isolated in 1803 by the German pharmacist Friedrich Adam. Named it 'morphium' after Morpheus, the Greek god of dreams.
Opioids - Morphine Plasma levels do not correlate with clinical effect. Low lipid solubility causes slow equilibration across BBB. Metabolized in the liver by conjugation. Morphine-6-glucuronide (active).
Remifentanil Piperidine derivative. Selective mu-receptor agonist. Potency similar to fentanyl. Terminal half-life < 10 min. Rapid blood-brain equilibrium. Metabolised by non-specific esterases.
Remfentnil Acid 95% 1.5%
Sufentanil 34 min Alfentanil 59 min Duration of infusion (minutes) Time to 50% drop in concentration at effect site (minutes) Fentanyl 262 min Remifentanil 3.7 min Plasma concentration after long term infusion After 240 min Context –sensitive half-time
Unwanted side-effects of opioids Respiratory depression Confusion Vasodilation Gut motility depression Opioids
Benzodiazepines; Midazolam Water-soluble lipid soluble in the body. Produces sedation, anxiolysis and amensia. Withdrawal agitation.