Outline the differences in the assessment and management of poisoning from substance ingestion in the following clinical scenarios, compared with a healthy young adult:

a) 2-year-old child. (30% marks)

b) 30-week gestation pregnant female. (35% marks)

c) 75-year-old adult with chronic kidney disease. (35% marks)

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College Answer

2-year-old child                                                                                                     

  • Ingested agent likely to be non-pharmaceutical
  • Vast majority of ingestions are benign
  • Other children may be affected (siblings, playmates)
  • Doses ingested likely to be small (2-3 tablets or small handful) and toxic effects mg/kg the same as adults but some agents can be potentially lethal for a toddler if even 1-2 tablets taken (e.g. amphetamines, Ca channel blockers, sulphonylureas) or a mouthful (e.g. organophosphate insecticides, eucalyptus oil, one mothball)
  • Unlikely to obtain accurate dosing history – risk assessment and management based on “worst-case scenario”
  • Need admission to health care facility with resources for paediatric resuscitation
  • Regular check of blood sugar levels
  • Usual toxicology screening tests for adult patient not necessary
  • GI decontamination with activated charcoal is not routine because of increased risks with aspiration – reserved for severe or life-threatening poisoning where supportive care or antidote treatment alone is inadequate
  • If severe intoxication suggesting large, repeated or unusual exposure, consider NAI

 

30/40 pregnant female                                                                                       

  • Risks to mother and foetus
  • Pregnancy-induced physiological changes impact on drug pharmacokinetics
  • Delayed gastric absorption and GI transit time slows drug absorption and increases period of potential benefit for decontamination
  • Increased blood volume increases VD and decreases drug plasma levels
  • Dilution of plasma proteins increases free drug levels 
  • Hepatic enzyme systems altered by circulating hormones
  • Increased cardiac output increase renal blood flow and GFR
  • Hypovolaemia and respiratory compromise may go unrecognised until at a late stage
  • A few agents pose increased risk to foetus and treatment threshold is lowered (e.g.
  • salicylates, CO, lead, MetHb-inducing agents)
  • Excellence in supportive care for the mother ensures best outcome for foetus
  • Obstetric and neonatal as well as toxicology input needed including decision for emergency delivery of baby.

 

75-year-old with CKD                                                                                           

  • Limited physiological reserve, deteriorating cognition, multiple co-morbidities and polypharmacy lead to exaggerated and unpredictable response in poisoning
  • More severe clinical course for same dose of same agent taken by healthy young adult
  • Pharmacokinetic changes with ageing and CKD o Delayed GI absorption o Decreased protein binding and increased free drug levels o Reduced liver function with decreased drug metabolism o Reduced renal function and reduced elimination o Baseline CKD likely to be made worse o “Therapeutic” drug doses may be toxic
  • Pharmacodynamic differences from drug effects on impaired organs e.g. poor ability to respond to CVS, respiratory and CNS depressant agents
  • Greater incidence of complications e.g. delirium, pneumonia, thrombo-embolism
  • Longer ICU and hospital stay

 

Discussion

This is another one of the questions in this paper which had a 0% pass rate. Locally available resources include the following chapters:

The answer would probably work better as a table:

A Comparison of Toxicological Differences
Group Infant/toddler Pregnant woman Elderly
Absorption
  • Cutaneous  absorption is more rapid
  • Intramuscular depot absorption is more rapid
  • Increased absorption by inhalation
  • Delayed absorption
  • More complete absorption (slower gut transit)
  • Slowed gastric emptying rate
  • Slowed gut transit
  • Gastric pH is lower
  • Transcutaneoius absorption is slow
Distribution
  • VD is greater for water soluble drugs
  • VD is smaller for fat-soluble drugs
  • Decreased protein binding
  • The blood brain barrier is immature
  • Increased volume of distribution
  • Decreased protein binding
  • Foetal pH causes "ion trapping"
  • VD changes: fat increases, water decreases
  • Protein binding is decreased
  • Predictive equations become inaccurate
Clearance
  • Rates of drug metabolism are increased
  • Altered hepatic clearance (due to hormones)
  • Increased renal clearance
  • Breastfeeding must be considered
  • Slowed hepatic clearance
  • Slowed renal clearance
Pharmacodynamics
  • Respiratory depression occurs more readily
  • Hypoglycaemia occurs more readily
  • Cardiovascular collapse occurs more precipitously
  • Paradoxical reaction to benzodiazepines and antihistamines
  • Foetal exposure is determined by maternal blood levels.
  • Teratogenicity of drugs must be considered
  • Increased  toxic effects
  • Decreased physiologic reserve
Pattern of poisoning
  • Accidental, or "exploratory"
  • Small in scale
  • Aspiration is more serious than the actual poisoning.
  • There are a few drugs which pose a greater threat to the foetus than the mother:  
    • Carbon monoxide
    • Methaemoglobin-inducing agents
    • Lead
    • Salicylates
    • Valproate
  • Accidental double dosing (due to poor memory)
  • Toxicity of a usually "safe dose"
  • Drug interactions
  • Outdated and discontinued drugs
  • Over the counter drugs
  • Opportunistic ingestion of random substances
Differences in approach
  • Overdose is considered in any child with unexplained obtundation
  • Early airway protection
  • NG charcoal only in the conscious and cooperative (or intubated) child
  • Naloxone 1-2mg IV - i.e. around 0.1mg/kg,
  • Dextrose 50%
  • Almost all of the antidotes to the various toxins are FDA pregnancy-risk category C, 
  • The exceptions are N-acetylcysteine, glucagon and naloxone (category B).
  • Emegency delivery needs to be considered to defend the foetus
  • Assisted clearance (eg. dialysis) may be required
  • ICU stay will be longer
  • Mortality is greater
  • Side-effects from decontamination are greater
       

References

References

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