Knowledge
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There has been some observational evidence that a greater depth of anesthesia, as measured by BIS, may be associated with an increase in post-operative mortality. In particular the association of the "triple low state" (low BIS, low volatile-ET, low MAP) with post-operative mortality is worrying.
Completion of the Balanced Anaesthesia Study Group’s large RCT looking at this issue however brings us as close to a final word as we may expect. Short et al. (2019) showed no difference in 1-year mortality for older patients undergoing major surgery, whether they received a deep (BIS target 35) or light (BIS target 50) general anaesthetic.
It is likely that earlier observational studies were showing the consequences of intraoperative hypotension resulting from anaesthetic depth, rather than anaesthetic depth itself.
summary
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An extensive collection of research debunking a range of myths and misconceptions regarding the way we use neuromuscular blocking drugs.
- Myth 1: Modern relaxants are so reliable and predictable that monitoring is unnecessary.
- Myth 2: Post-op residual paralysis is neither common or important.
- Myth 3: Post-op residual paralysis is easy to identify.
- Myth 4: Sugammadex makes residual paralysis a non-issue. (it might, but only if it is routinely available and used!)
- Myth 5: Using propofol and remifentanil we can avoid relaxants for intubation all together.
- Myth 6: Neuromuscular blockade has no effect on BIS.
And bonus myth: deep relaxation is necessary for improving surgical access during laparoscopy.
summary
...and 1 more note
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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.
A. Physiochemistry
- pKa - 8.5 (9% nonionised @ 7.4)
- Octanol water coefficient - 39 (so 40x lipid solubility of morphine)
- phenylpiperidine opioid
B. Pharmacokinetics
- 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)
C. Pharmacodynamics
- 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.
- vasodilation
- tachycardia
- depress myocardial contractility
- Resp - potent resp depressant - greater effect on TV than RR. Histamine release. Chest wall rigidity.