A. Physiochemistry

• pKa - 7.3 (58% nonionised @ 7.4)
• Octanol water coeff - 18
• phenylpiperidine opioid
• contain 2 ester bonds so hydrolysed by non-specific tissue esterases.
• Preparation contains 'glycine', so cannot be used epidurally.
• White powder for reconstitution with water - 1, 2, 5 mg packs

B. Pharmacokinetics

1. Dose: (100x morphine potency, ~equal to fent)   - TCI: 3-8 ng/mL     - (up to 15 ng/mL for very stimulating procedures)     - Spontaneous ventilation returns @ 1-2 ng/mL   - 0.1-0.3 mcg/kg/min infusion (with propofol 80 mcg/kg/min (= 34 mL/h for 70 kg).
   • 0.01-0.05 mcg/kg/min spont vent
   • dilute 1 mg to 50 mL = 20 mcg/mL, or 5 mg in 50 mL = 100 mcg/mL.
   • paeds: 0.03 mg/kg in 50 mL then 1 mL/h = 0.01 mcg/kg/min.
   • Or paediatric whole-ampoule dilutions when advanced pumps are unavailable:
   • 1mg in 16.7mLs
   • or 2mg in 33.3 mLs
   • or 3mg in 50mLs 
   • → to give a dilution of 60mcg/mL
   • then for a patient of XYkg running at X.Y mLs/hr is 0.1mcg/kg/min. eg. for a 42kg patient running at 0.1mcg/kg/min will be 4.2mLs/hr which over 4 hrs uses 16 mL so a 1mg ampoule would be sufficient.
   • 1 mcg/kg IV bolus to blunt pressor resp to intubation, better than fentanyl. (equiv. fent 2 mcg/kg, alfent 20 mcg/kg)
   • 3-5 mcg/kg for intubation with propofol 2 mg/kg.
   • 0.2-0.8 mcg/kg bolus for PCA analgesia (++SEs: sedation, desaturation)
2. Absorption - IV
3. Distribution - 0.5 L/kg (small)
4. Protein binding - 70-90%
5. Onset 1-4 min; Offset 4 min (offset due to metab not redist)
6. Metabolism - ß½ ~10 min. (CSHT-8h only 4 min!) Metabolised by non-specific plasma esterases to almost-inactive metabolites (GR90291: 1/4600 activity! / t½ 2h).
   • Minor pathway - N-dealkylation. NOT metabolised by plasma cholinesterase.
7. Clearance - 42 mL/min/kg (30-50% CO)

C. Pharmacodynamics

1. Mech - highly selective mu agonist.
2. CVS - dec MAP & HR 20-30%. (? low dose glycopyrrolate to attenuate brady).
   • No histamine release.
3. CNS
   • max MAC reduction ~ 85% (0.1-0.2 mcg/kg/min = 60-70% MAC reduction).
   • To avoid awareness keep propofol @ at least 80 mcg/kg/min or volatile 0.3 MAC.
   • Sedation.
   • Beware rapid Opioid Induced Hyperalgesia.
4. Resp - ⇣ RR & MV; apnoea. Spontaneous respiration occurs at blood concentrations of 4 to 5 nanogram/mL in the absence of other anaesthetic agents; for example, after discontinuation of a 0.25 microgram/kg/minute infusion of remifentanil, these blood concentrations would be reached in two to four minutes.
5. GIT - dec CTZ stimulation as rapidly metabolised; no ion trapping.
6. Muscle - muscle rigidity similar to alfentanil, though more than fentanyl.
   • May cause chest wall rigidity (inability to ventilate) after single doses of > 1 microgram/kg administered over 30 to 60 seconds or infusion rates > 0.1 microgram/kg/minute.
   • Administration of doses < 1 microgram/kg may cause chest wall rigidity when given concurrently with a continuous infusion of remifentanil.
7. Foetal - little effect as rapidly metabolised by foetus.