The remifentanil PCA for labour analgesia controversy continues...
Those advocating its first-line use point to reassuring evidence of maternal satisfaction and acceptability, reduced epidural rates, and some suggestion of reduced instrumental delivery rates.
For the negative, the ongoing safety concerns created by routine use of remifentanil PCAs are foremost, particularly given how uneven hospitals can be at implementing best safety practices. Observed rates of significant desaturation range from 25-70%, in addition to potential neonatal effects.
The greatest challenge facing the remiPCA advocates, is that the labour epidural is still the most effective form of labour analgesia, and has only improved over the decades as safety has been both maintained and increased.summary
- 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
- 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)
- Absorption - IV
- Distribution - 0.5 L/kg (small)
- Protein binding - 70-90%
- Onset 1-4 min; Offset 4 min (offset due to metab not redist)
- 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.
- Clearance - 42 mL/min/kg (30-50% CO)
- Mech - highly selective mu agonist.
- CVS - dec MAP & HR 20-30%. (? low dose glycopyrrolate to attenuate brady).
- No histamine release.
- 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.
- Beware rapid Opioid Induced Hyperalgesia.
- 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.
- GIT - dec CTZ stimulation as rapidly metabolised; no ion trapping.
- 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.
- Foetal - little effect as rapidly metabolised by foetus.
- Remifentanil infusions above 0.20-0.25 μg/kg/min are associated with hyperalgesia (OIH = Opioid Induced Hyperalgesia) and tolerance (AOT = Acute Opioid Tolerance) respectively.
- Some of these effects can be mitigated by multimodal analgesia (notably ketamine), and possibly by gradual weaning of a remifentanil infusion.
- The findings have been predominately identified in rats and volunteer human studies. The clinical and longterm significance is still uncertain.
- Although OIH and AOT arise from different physiological mechanisms, they are clinically difficult (if not impossible) to differentiate.
- The clinical priority for management is prevention.
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