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reference
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Collection: Pethidine/Meperidine
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
1. Dose - 25-100 mg (10% morphine potency). Limit 1000 mg 1st day, then 600 mg/day there after.
2. Absorption - IV, IM, epidural, po (55% biov)
3. Distribution - Vdss 4.5 L/kg. Crosses placenta - foetal 80% of maternal.
4. Protein binding - 60%
5. Onset 10 min ; Offset 2-3 h
6. 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.
7. Clearance - 20 mL/kg/min (same as morph & fentanyl)
C. Pharmacodynamics
1. Mech - mu and kappa agonist, causing potent spinal and supraspinal analgesia.
2. 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)
3. 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
4. Resp - potent resp depressant - greater effect on TV than RR. Histamine release. Chest wall rigidity.
  Daniel Jolley
reference
1
Collection: Sufentanil
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.
• 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.
  Daniel Jolley
pearl
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Simple measurement of cortical functional connectivity will not be enough to assess adequacy of general anesthesia.
Vlisides PE, Li D, Zierau M et al. Dynamic Cortical Connectivity during General Anesthesia in Surgical Patients. Anesthesiology. 2019 Jun 1; 130 (6): 885-897.
  Daniel Jolley
pearl
1
A single pediatric general anesthetic exposure is associated with increased parental-reported behavioural changes though no difference in general intelligence.
Ing C, Jackson WM, Zaccariello MJ et al. Prospectively assessed neurodevelopmental outcomes in studies of anaesthetic neurotoxicity in children: a systematic review and meta-analysis. Br J Anaesth. 2021 Feb 1; 126 (2): 433444433-444.
  Daniel Jolley
pearl
1
Subcutaneous GTN may assist paediatric radial artery cannulation and improve first pass success.
Jang YE, Ji SH, Kim EH et al. Subcutaneous Nitroglycerin for Radial Arterial Catheterization in Pediatric Patients: A Randomized Controlled Trial. Anesthesiology. 2020 Jul 1; 133 (1): 53-63.
  Daniel Jolley
pearl
1
Videolaryngoscopy may improve first-pass success in the ICU and among less experienced practitioners outside the operating theatre.
Arulkumaran N, Lowe J, Ions R et al. Videolaryngoscopy versus direct laryngoscopy for emergency orotracheal intubation outside the operating room: a systematic review and meta-analysis. Br J Anaesth. 2018 Apr 1; 120 (4): 712-724.
  Daniel Jolley
pearl
1
Videolaryngoscopy in children and neonates reduced intubation trauma & improved indirect glottic view, although demonstrated no other benefits.
Hu X, Jin Y, Li J et al. Efficacy and safety of videolaryngoscopy versus direct laryngoscopy in paediatric intubation: A meta-analysis of 27 randomized controlled trials. J Clin Anesth. 2020 Nov 1; 66: 109968.
  Daniel Jolley
pearl
1
GlideScope-Titanium videolaryngoscopy improved glottic visualisation but prolonged intubation time for placement of double lumen tubes.
Risse J, Schubert AK, Wiesmann T et al. Videolaryngoscopy versus direct laryngoscopy for double-lumen endotracheal tube intubation in thoracic surgery - a randomised controlled clinical trial. BMC Anesthesiol. 2020 Jun 16; 20 (1): 150.
  Daniel Jolley
reference
1
Collection: Morphine
Morphine is one of the most commonly used opioids worldwide. First isolated in 1803 and commercially marketed by Merck in 1827.
A. Physiochemistry
• Natural phenathrene opioid - plant, animal and even human synthesis identified.
  • Synthesized by mammalian cells from dopamine, although exact role unclear.
• pKa - 7.9 (20% nonionised @ 7.4)
• Octanol water coefficient - 1.4 (relatively low lipid solubility compared with other opioids)
• 3 rings attached to piperidine ring with a tertiary amine.
B. Pharmacokinetics
1. Dose - 50 mcg/kg IV
   • analgesia @ [plasma] 0.05 mcg/mL
   • epidural: 10-20 mcg/mL
   • PCA adult: 50 mg in 50 mL; 1 mL (1 mg) bolus 5 min lockout, commonly used.
   • PCA paeds: 1 mg/kg in 50 mL; 1 mL (20 mcg/kg) bolus; background 0.5-1 mL/h (10-20 mcg/kg/h).
2. Absorption - IV, IM, s/c, po (3x dose as HER 0.69)
3. Distribution - Vdcc 0.3, Vdss 3.5 L/kg
4. Protein binding - 30% (albumin)
5. Onset: peak onset at 20 min when given parenteral, 60 min orally; Offset 4 h
6. Metabolism - t½α 10-20 min, t½ß 2-4 h
   • 75% metabolised by conjugation → 90% morphine-3-glucuronide (no activity)
   • 10% morphine-6-gluc (13x potency of morphine). MAOIs inhibit glucuronidation.
7. Clearance - 15 mL/kg/min
C. Pharmacodynamics
1. Mech - mu, kappa, delta agonist. (GI linked). Effective against visceral, skeletal & joint pain.
2. CNS - little CNS penetration (cf. heroin, which readily crosses BBB), although alkalisation (⇣pCO2) ⇡ non-ionised fraction, and ⇡pCO2 ⇡CBF. Both ⇡ cerebral morphine concentration.
   • 'Ceiling effect' on EEG reaching high voltage, slow frequency (delta 2-4 Hz) waves.
   • ⇣ CMRO2 & ⇣ ICP.
   • ⇡ cortical stimulation of Edinger-Westphal nucleus → miosis.
3. CVS - ⇣ SNS & ⇡ PNS tone. Bradycardia, venodilation, histamine release (causes ⇣ MAP). Orthostatic hypotension due to depression of SNS responses. Direct depressant effect on SA node, slowing conduction (⇡ VF risk).
   • Administration with N₂O results in CVS depression.
4. Resp - Respiratory depression & response to CO₂ & hypoxia (shift pCO₂/VA curve to right).
   • Bronchoconstriction due to histamine release (similar with pethidine). Depresses airway reflexes & ciliary reflexes.
5. Renal - diuresis (kappa receptors → ADH release)
6. GIT - Nausea & vomiting due to stimulation of CTZ (30-40% of subjets); ileus; constipation; sphincter of Oddi spasm.
7. Pruritus
  Daniel Jolley
pearl
1
Red-haired patients show no greater risk of intraoperative awareness than other phenotypes.
Gradwohl SC, Aranake A, Abdallah AB et al. Intraoperative awareness risk, anesthetic sensitivity, and anesthetic management for patients with natural red hair: a matched cohort study. Can J Anaesth. 2015 Apr 1;62(4):345-55.
  Daniel Jolley