Question 28

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)

[Click here to toggle visibility of the answers]

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 V_D 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

Kearns, Gregory L., et al. "Developmental pharmacology—drug disposition, action, and therapy in infants and children." New England Journal of Medicine 349.12 (2003): 1157-1167.

Barry, J. Dave. "Diagnosis and management of the poisoned child." Pediatric annals 34.12 (2005): 937-946.

Reid, David HS. "Treatment of the poisoned child." Archives of disease in childhood 45.241 (1970): 428.

Henretig, Fred M. "Special considerations in the poisoned pediatric patient." Emergency medicine clinics of North America 12.2 (1994): 549-567.

Calello, Diane P., and Fred M. Henretig. "Pediatric toxicology: specialized approach to the poisoned child." Emergency medicine clinics of North America 32.1 (2014): 29-52.

Shieh-Czaja, Angela, Diane P. Calello, and Kevin C. Osterhoudt. "Sick sisters." Pediatric emergency care 21.6 (2005): 400-402.

Anderson, Gail D. "Pregnancy-induced changes in pharmacokinetics." Clinical pharmacokinetics 44.10 (2005): 989-1008.

Goldfranks Manual of Toxicologic Emergencies: 2007 Edition, Ch. 30: "Reproductive and Perinatal Principles"

Zelner, Irene, et al. "Acute poisoning during pregnancy: observations from the toxicology investigators consortium." Journal of medical toxicology 11.3 (2015): 301-308.

Klein-Schwartz, Wendy, and Gary M. Oderda. "Poisoning in the elderly." Drugs & aging 1.1 (1991): 67-89.

Ticehurst, Stephen, et al. "Elderly patients with deliberate self-poisoning treated in an Australian general hospital." International psychogeriatrics 14.1 (2002): 97-105.

Carlsten, A., Margda Waern, and P. Allebeck. "Suicides by drug poisoning among the elderly in Sweden 1969–1996." Social psychiatry and psychiatric epidemiology 34.11 (1999): 609-614.

Jansen, Paul AF, and Jacobus RBJ Brouwers. "Clinical pharmacology in old persons." Scientifica 2012 (2012).

Sotaniemi, Eero A., et al. "Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions." Clinical pharmacology and therapeutics 61.3 (1997): 331-339.

Mitchell, Rebecca J., et al. "Dementia and intentional and unintentional poisoning in older people: a 10 year review of hospitalization records in New South Wales, Australia." International Psychogeriatrics 27.11 (2015): 1757-1768.

Rogers, Jody J., and Kennon Heard. "Does age matter? Comparing case fatality rates for selected poisonings reported to US poison centers." Clinical toxicology 45.6 (2007): 705-708.

Doak, Martin W., et al. "Self-poisoning in older adults: patterns of drug ingestion and clinical outcomes." Age and ageing 38.4 (2009): 407-411.

[Submit a comment or correction]