- pKa - 8.5 (9% nonionised @ 7.4)
- Octanol water coefficient - 39 (so 40x lipid solubility of morphine)
- phenylpiperidine opioid
- Dose - 25-100 mg (10% morphine potency). Limit 1000 mg 1st day, then 600 mg/day there after.
- Absorption - IV, IM, epidural, po (55% biov)
- Distribution - Vdss 4.5 L/kg. Crosses placenta - foetal 80% of maternal.
- Protein binding - 60%
- Onset 10 min ; Offset 2-3 h
- Metabolism - ß½ 3 h; N-demethylation to norpethidine and then hydrolysis to norpethidinic acid; also direct hydrolysis to pethidinic acid. Renal elimination.
- Norpethidine - ß½ 15 h; 50% analgesic properties, 2x convulsant effects.
- Clearance - 20 mL/kg/min (same as morph & fentanyl)
- Mech - mu and kappa agonist, causing potent spinal and supraspinal analgesia.
- CNS - more euphoria, less N/V than morphine. No miosis, but may cause mydriasis (pupil dilation -atropine-like kappa action). No EEG changes like morphine. ⇡ latency & amplitude of SSEPs.
- NB: has LA action, so can be used as sole agent for neuroaxial block.
- anti-shivering effect (kappa)
- CVS - ⇣ MAP (> than morphine) due to histamine release & alpha adrenergic blockade (vasodilation). Inc HR (atropine like effect). Large doses depress myocardial contractility. May cause hypertensive crisis in those on MAOIs.
- depress myocardial contractility
- Resp - potent resp depressant - greater effect on TV than RR. Histamine release. Chest wall rigidity.
- OWC 1800
- pKa 8.0
- Potency 5-10x fentanyl, 500x morphine.
- Vd 3 L/kg
- Protein binding 93%
- Clearance 12 mL/kg/min
- tß½ 3 hours
- CSHT(8h) 30 min (alfentanil ~60 m)
- mu agonist, also stimulates serotonin release and at high dose has local anaeshetic effect.
- Structurally different from fentanyl, with a methoxymethyl group on the piperidine ring (increases potency and reduces duration of action) and thiophene instead of phenyl ring.
Interventions to stiffen the surface during CPR delivery have limited effect on chest compressions in manikin trials.
Surgery should be delayed for at least 7 weeks after COVID, although those with persistent COVID symptoms will still have more than twice the 30-day mortality than those without.
Kataife et al. (2021) describe a cognitive aid for better managing perioperative haemorrhage, the Haemostasis Traffic Light algorithm. Using a simulation-based RCT across two centres (University Hospital Zurich & the Italian Hospital of Buenos Aires, N=84), they showed that using the HTL improved case solutions (OR 7.23, 3.82-13.68), quickened therapeutic decisions, (HR 1.97, 1.18-3.29), improved therapeutic confidence, (OR 4.31, 1.67-11.11) and reduced workload perception.
The aim of the HTL is to improve both situational awareness and decision making, by integrating clinical judgement and point-of-care testing (ROTEM) within an accessible, structured algorithm.
Haemostasis Traffic Light takeaway:
Kataife's study again shows the benefit of cognitive aids, particularly in critical, time-sensitive situations. The anaesthesia and critical care community's historical resistance to decision-support tools requires challenge.
The Haemostasis Traffic Light is a cognitive aid integrating clinical judgement & point-of-care testing to improve management of periooperative bleeding.
Interesting Cochrane meta-analysis looking at PONV prophylaxis from German (Weibel et al. 2021) that included almost 100,000 study participants across 585 trials. Interesting not so much because it confirms much of what we already new (or assumed, based on our common PONC prophylaxis drug choices), but because it reassures us that side-effects from commonly used PONV drugs are low to non-existent.
Takeaway: granisetron is probably the best single-agent or in combination with other agents because of it's efficacy (better than ondansetron), low-cost, long duration, and absent side-effects.
Aprepitant (NK1), ramosetron (5HT3), granisetron (5HT3), ondanestron (5HT3) & dexamethasone (steroid) all significantly reduce postoperative nausea & vomiting when used as prophylaxis with a high evidence certainty.
Multiple advantages to cuffed ETT in children when compared to dogmatic alternative.
Pethidine (Meperidine) is a phenylpiperidine synthetic opioid first synthesized in 1938. Although widely used in the 20th century, it has fallen out of favour over the past decade due to abuse potential, limited advantages over other opioids and the existence of toxic metabolites.
Sulfentanil is a potent, short-acting synthetic opioid used in anesthesia and critical care. First synthesized by Janssen Pharmaceutica in 1974. It is the most potent opioid licensed for use in humans.
Simple measurement of cortical functional connectivity will not be enough to assess adequacy of general anesthesia.