Knowledge
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Attention Deficit and Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterised by inattention, hyperactivity, and impulsivity. It is most commonly diagnosed in childhood, with a male predominance (approximately 2-3:1), though symptoms often persist into adulthood. Global prevalence is estimated at ~5-7% in children and ~2-3% in adults. Meta-analyses show ADHD is primarily genetic with 70–80% heritability.
Anesthesia issues
- Medication considerations
- Stimulants (methylphenidate, amphetamines)
- May increase sympathetic tone (tachycardia, hypertension, arrhythmias)
- Possible attenuation of response to indirect-acting vasopressors (e.g. ephedrine, metaraminol); prefer direct-acting agents (phenylephrine, epinephrine)
- Withdrawal or omission perioperatively may cause fatigue, irritability, behavioural instability.
- Possible altered anaesthetic requirements; stimulants may increase MAC slightly, though evidence is inconsistent.
- Non-stimulants (atomoxetine, guanfacine, clonidine) - α2-agonists (guanfacine, clonidine) can potentiate sedation and hypotension.
- Stimulants (methylphenidate, amphetamines)
- Behavioural and perioperative management
- Difficulty with preoperative cooperation and anxiolysis (may need structured preparation, early anxiolytic use, or parental presence in paediatrics); Increased anxiety or agitation in unfamiliar environments.
- Impulsivity may increase risk of perioperative non-adherence (e.g. fasting rules, device removal).
- Higher risk of emergence agitation or delirium, especially in children.
- May display increased postoperative anxiety, irritability, or oppositional behaviour
- Pain perception and reporting may be inconsistent, complicating assessment and analgesia planning.
- Comorbidities
- High association with anxiety, depression, and substance use disorders (impact on anaesthetic planning and perioperative risk)
- Sleep disturbances common, may complicate recovery and pain management
- Medication considerations
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From the best-available current evidence (Ahlqvist 2024): NO
The American Academy of Obstetrics and Gynecology's journal ACOG, summarises it best in Damkier et al.'s 2025 review article:
"According to the current scientific evidence, in utero exposure to acetaminophen is unlikely to confer a clinically important increased risk of childhood ADHD or ASD." - Damkier (2025)
Ahlqvist et al's 2024 Swedish cohort study of 2.48 million children showed that when controlling for family confounders by using sibiling controls, there was no association between paracetamol/acetaminophen use and various neurodevelopmental problems:
"Acetaminophen use during pregnancy was not associated with children's risk of autism, ADHD, or intellectual disability in sibling control analysis." - Ahlqvist (2024)
The problem with many of the earlier (and often contradictory) studies that showed a possible association, was that by necessity these were observational studies that struggled to control for confounders. The classic "association is not causation" trap. Ahlqvist et al's very large study, while still observational, uses matched sibling controls to neutralise "unobserved confounding" – and reassuringly, the association dissapears.
Nonetheless, it’s worthwhile being aware of the body of evidence and how it has evolved over the last decade. Professional obstetric organisation advice remains unchanged: paracetamol is appropriate to use in pregnancy when managing fever and pain, which untreated have their own detrimental fetal effects.
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Tapentadol (Palexia™, Nucynta™) is a synthetic opioid agonist and noradrenaline-reuptake inhibitor. Similar to and based upon tramadol, although with much weaker inhibition (by design) of serotonin reuptake.
A. Physiochemistry
- Synthetic analgesic of 'amino-cyclo-hexanol' group.
- Unlike tramadol, prepared as only the (R,R) stereoisomer (weakest opioid activity).
- Oral: 50, 75 & 100 mg immediate release, and 50,100,150 & 200 mg extended release preparations.
- No parenteral preparation is approved for use.
B. Pharmacokinetics
- Dose: 50-200 mg bd/qid for immediate release preparations, 50-200mg bd for extended release.
- approximately double potency of tramadol, similar to oxycodone and between tramadol and morphine.
- Absorption - po (only 32% biov)
- increasing doses have a non-linear effect on increasing peak plasma concentration, thus higher doses result in disproportionately higher Cmax.
- Distribution - ~8 L/kg (higher than tramadol).
- Protein binding - 20% (low!)
- Onset 30 min; Offset 4-6 h
- Metabolism - t½ 4h
- hepatic conjugation with glucuronic acid → glucuronides is main pathway (tapentadol-O-glucuronide); p450 metabolism to N-desmethyl tapentadol and hydroxyl tapentadol.
- No known active metabolites
- 99% excreted in urine, 1% in faecies.
- Clearance - 22 mL/kg/min
C. Pharmacodynamics
- Mech - weak mu agonists (30% of action / 18x less affinity than morphine) ; inhibits NAd reuptake (through indirect activation of post-synaptic alpha-2 adrenoreceptors), activating descending NAd (70%) modulating pain pathways.
- CNS - analgesia, good for neuropathic pain, low(er) incidence of tolerance & dependence, lowers seizure threshold, dizziness, sweating, ⇡ ICP.
- CVS - few CVS effects. Some tachycardia and flushing.
- Resp - little respiratory depression.
- Renal - possible caution in renal failure, although no active metabolites even if 99% renal excreted.
- GIT - Nausea & vomiting (less than tramadol), minimal constipation, more biliary spasm than tramadol.
- SEs - interacts with MAOI (adrenergic storm), SSRIs (serotonin syndrome).
- Although thought to have less abuse potential than other common opioids, it is still classed as a Schedule 2 drug in the US, Schedule 1 in Canada, Class A controlled drug in the UK and S8 in Australia.
- Safety of tapentadol in pregnant, lactating women, and pediatric patients is not yet established.
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Articles of interest relevant to labor epidural analgesia, both specifically focusing on obstetric epidurals and more peripherally relevant to obstetric labor analgesia.
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