Paracetamol toxicity

Emergency medicine, General paediatrics

Common choice for intentional overdose – mostly young women but males and older adults tend to take bigger amounts…

Acetylcysteine almost universally effective when administered within 8-10 hours – but occasional acute liver failure, with high mortality and still one of the most common reasons for hyperacute liver transplant.

Usually no symptoms in first 24 hours after ingestion – by which time the stress that triggered the ingestion has usually passed… Then just nausea, vomiting- not at all clear that acute liver injury is progressing. Abdominal pain then develops (jaundice unusual).

With very large overdoses, can present early with altered mental status or metabolic acidosis.

With overdoses taken in staggered doses (over more than 1-2 hours) risk higher and nomogram unreliable. Paracetamol level x ALT predictive?

Acute kidney injury is seen with acute liver injury (hepatorenal syndrome) but sometimes is main issue (acute tubular necrosis caused by local CYP450 activation).

CYP450 enzymes produce toxic metabolites. Glutathione is natural antidote but once it is used up cell death starts to occur.

Scottish & Newcastle antiemetic protocol (SNAP) – higher initial acetylcysteine dosing (first bag over 2 hours, second bag over 10 hours – cf prev 21 hour regimen), less anaphylactoid reactions. Current HiSNAP trial looking at even higher doses.

Haemodialysis can be considered in severe metabolic acidosis and high paracetamol levels (>900mg/L) but also removes acetylcysteine so dose needs to be doubled.

Co-ingestion of opiates or anticholinergics may delay absorption, so repeat level?

Low body weight tend to get fluid overloaded. Use saline rather than dextrose

Nomograms vary internationally – UK more conservative than US/Australia.

Activated charcoal useful in acute ingestion (<4 hours) or massive overdose.

Anaphylactoid reactions caused by non-immune histamine release – urticaria, flushing, bronchospasm, but not upper airway compromise, angioedema or hypotension. Not a contraindication to repeat treatment.

INR >3 or ALT >1000 are high risk for liver failure, even before encephalopathy develops.

Neurofibromatosis

General paediatrics, Genetics, Neurology

Autosomal dominant condition, so 50% risk of passing on to offspring and variable penetrance. May be spontaneous mutation.

Diagnosis still essentially clinical: 1988 Consensus is for any 2 of the following:

  • 6 or more cafe-au-lait spots (at least “pencil thickness” in diameter?)
  • axillary or groin freckling
  • 2 or more Lisch nodules – pigmented lesions in iris, may need slit lamp to see. No clinical consequence!
  • 2 or more neurofibromas,
  • optic pathway glioma (OPG),
  • bone dysplasia,
  • first-degree family relative with NF1 

Plexiform neurofibromas are larger ones with potential to cause visual, hearing, even cardiac problems.

Issues are:

  • High blood pressure
  • Epilepsy (lesions develop in brain)
  • Bone problems including scoliosis
  • Effects of neurofibromas in sensitive locations
  • Cosmetic appearance, self image
  • Cancer (malignant change in neurofibroma but also brain and breast)
  • Risk to own children

Ophthalmology review annually in children, every 2 yrs in adults, given risk of optic gliomas.

Family support at https://nervetumours.org.uk/

Clinical trial of selumetinib had beneficial effect on inoperable plexiform fibromas.

Status Epilepticus

Emergency medicine, General paediatrics, Neurology

Resus council guideline 2021.

Definition (convulsive) – seizure lasting more than 5 minutes. Used to be 30 minutes! Unlikely to terminate spontaneously after 5 minutes. Evidence that the longer it lasts, the hard it is to treat.

Use existing seizure management plan, if there is one!

Buccal midazolam (0.3-0.5mg/kg depending on age) and IM/IO lorazepam 0.1mg/kg – max 2 doses of benzo’s, including any home/prehospital doses.

If no response to first dose after 5 minutes, go for IV lorazepam and prepare next step.

2nd line should then be within 15 minutes of start of seizure – Levetiracetam, phenytoin, phenobarb.

Phenytoin needs to go slowly (over 20 mins – risk of brady/asystole) cf levetiracetam (over 5 mins). Call anaesthetist.

After 5 mins, either try alternative or go for intubation and deep sedation: RSI with thiopental, or propofol +/- rocuronium. Ketamine and midaz given as alternatives as no evidence for 3rd line agent!

Meanwhile – check glucose, sodium, calcium/Mg (if sepsis). Temperature control.

Beware CNS haemorrhage (trauma?), raised intracranial pressure, meningitis, encephalitis.

[no rectal medicines mentioned but paraldehyde worked pretty well back in the day]

Sleep-related hypermotor epilepsy

General paediatrics, Neurology

Onset around age 9.

Can be just waking up, possibly confused, but multiple times a night.

Easier to diagnose if more dramatic twisting, grimacing, thrusting movements, posturing. Can be wandering like parasomnia, can be vocalisations (screaming, moaning, crying).

Can be aware during seizure. Can be sensation of unable to catch breath.

Usually around 30 secs.

Often inherited (prev called autosomal dominant frontal lobe epilepsy). Not always frontal!

Probably needs video EEG.

See also Panayiotopoulos (occipital lobe) epilepsy.

Mast cell activation syndrome

General paediatrics, Immunology

Recurrent mast cell degranulation causing episodes of hives, diarrhoea, swelling, dizziness, even anaphylaxis.

Thought to be due to clonal expansion of abnormal mast cells, not requiring usual triggers.

Diagnosis is on basis of rise in tryptase levels during an episode from base line. If base line tryptase is normal, then likely mastocytosis. Urine mast cell products eg leukotriene, prostaglandin? Look for KIT D816V on flow cytometry. Bone marrow aspiration?

Scoring systems available.

Treatment is predictably:

  • Antihistamines, preferably non sedating. Some people however benefit from the additional sedative effect of older antihistamines eg ketotifen, hydroxyzine.
  • Adrenaline autoinjectors for anaphylaxis self management
  • Montelukast/zafirlukast has systemic anti-inflammatory action
  • Famotidine has anti-histamine action
  • Steroids for short term use
  • Omalizumab

Citrus allergy

Allergy, General paediatrics

Orange, mandarin, tangerine all varieties of orange. Seeds probably rich in allergens but less likely to be eaten (chewing probably also required for reaction)!

Various allergens identified, including profilin (so oral allergy syndrome) and LTP (more in Mediterranean, cross reacts with Pru p3, not surprisingly).

One letter briefly touches on citrus cross reactivity – some tolerate lemon and/or tangerine, some had oral symptoms with tangerine, none had tried grapefruit. So varying and not well explored…

G6PD deficiency

General paediatrics, Genetics, Haem/Oncology

Glucose 6 phosphate dehydrogenase deficiency. X-linked.

Can present with prolonged jaundice in babies. Otherwise with haemolysis (causing jaundice and anaemia).

Haemolysis triggered by infections, but also drugs and chemicals. Classically sulfonamides, but most relevant are:

  • Anti-malarials (ironically)
  • Nitrofurantoin!
  • Aspirin (so Kawasaki)
  • Henna! Other dyes
  • Moth balls!

Geographical risk areas –

Liminality

Generic, Health Literacy, Patients

Liminality in medicine is the idea that you can be between illness and wellness.

Paul Turner et al give the example of having a food allergy: people with allergies do not consider themselves fully ‘ill’ or entirely ‘well’, but something in between. They are typically “well” so long as they apply food safety skills to avoid their trigger food(s) – but a slip or mistake can lead to a reaction and potentially death from anaphylaxis.

With liminality, a young person feels set apart, or a family feels their child is different from others – this can impact on self image, social interaction, which in turn can lead to denial or other unhealthy coping strategies and adverse health outcomes.

[Sanders, Soc Sci Med 2019]

Air transmission

General paediatrics, Infectious disease

Aerosol and droplet transmission are no longer in fashion – to be replaced by single term “air transmission”.

Similarly, no longer a list of defined “aerosol generating procedures” – flowchart to come that looks at whether coughing is induced and whether “high speed device” used.

[First letter from new Public Services Delivery body?!]

Non traditional medicine and alternative health beliefs

Communication, Ethics, Generic, Health Literacy, Patients

Non-disclosure of use of traditional, complementary and/or alternative medicine (TCAM) is found in 20 to 77% of studies. This has been attributed to an anticipated negative or dismissive response; assumption that health care professionals lack knowledge on the subject; or the HCP not asking.

HCPs who take the time to listen attentively and respectfully are more likely to have patients disclose TCAM use.

Some cultures/religions are more likely to use TCAM, and are also more likely to suffer from heath inequalities and stigma. If seen as ‘alternative’ and contrary to mainstream medicine, discussion might be perceived by both patient and doctor as irrelevant. If perceived within a more ‘integrative’ framework, it is more likely that TCAM use will be a topic for discussion. The transition from a “traditional-alternative” to a “traditional-integrative” approach to care is being promoted by the World Health Organization’s Traditional Medicine Strategy (2014–2023).

Tangkiatkumjai et al. suggested that TCAM use can be accompanied by an expectation of benefit; perception of safety; and dissatisfaction with conventional medicine. Perception of safety can of course be very misguided, eg interactions between herbal products and cancer drugs.

In oncology, integrative programs focus on quality of life-related concerns, eg chemotherapy-induced peripheral neuropathy, preoperative anxiety and postoperative pain. These programs have been shown to increase patient adherence to oncology treatment regimens, within a safe and effective environment.

Patient trust in their HCP has been shown to increase when asked directly about TCAM use.

Try the LEARN (Listen, Explain, Acknowledge, Recommend, and Negotiate) model, proposed by Berlin and Fowkes.

Non-judgmental approach essential – stereotypes, prejudices, and misconceptions may compromise the therapeutic relationship.

Other family/community voices that can be included?

“What are your goals of treatment with TCAM? Is your primarily goal to relieve your symptoms and improve your quality of life? Or is it to “fight” or cure the disease, prolong life, “strengthen” your immune system, or another goal?”

[Humility about failures/faults of conventional medicine!] [Ben-Arye, 2024]