Management of Poisoning ✅ Flashcards
What can the clinical management of a poisoned child be broadly divided into?
- Achieving and supporting physiological and biochemical homeostasis
- Reduction of further absorption of the poison
- Enhancement of elimination of poison or its toxic metabolites
What is true in the management of most cases of poisoning?
Poisoning is mild, and requires little more than supportive care
What management used to be advocated for all cases of poisoning?
Aggressive gastric decontamination
Why is routine use of aggressive gastric decontamination no longer advised?
Due to limited evidence of benefit, and the possibility of significant harm
What should be taken into account when considering the use of aggressive gastric decontamination?
- The time and type of poison ingested
- The time since ingestion
- Assessment of risks of treatment vs non-treatment
Give 3 methods of aggressive gastric decontamination
- Gastric evacuation
- Intra-gastric binding
- Speeding transit of toxins to reduce total absorption time
How is gastric evacuation achieved?
- Forced emesis
- Gastric lavage
How is intra-gastric binding achieved?
Most commonly by administration of activated charcoal
How is transit time of toxins increased to reduce total absorption time?
- Whole bowel irrigation
- Cathartics
How is charcoal produced?
Controlled burning of high-carbon substances, e.g. sawdust or nutshells
How can charcoal be activated?
Heating it in a oxidising atmosphere
What results from activating charcoal?
A highly porous partible with an exceptionally high surface area
What is the surface area of 1g of charcoal?
950-2000m^2
How can activated charcoal be administered into the stomach?
- Swallowing
- NG tube
What is the purpose of administering activated charcoal into the stomach?
It has the ability to adsorb potentially poisoning substances, reducing their bioavailability and hence toxicity
What is required to maximise the efficacy of activated charcoal?
It needs to be in direct contact with as much of the poison as possible
How is it ensured that activated charcoal is in contact with as much of the poison as possible?
It is formulated as a powder dispersed in water (rather than a tablet or capsule)
When should activated charcoal be given in cases of poisoning?
As soon as possible after ingestion
After what time period post-ingestion is activated charcoal unlikely to result in significant reduction in systemic absorption?
More than one hour after ingestion
What are the criteria for considering the administration of activated charcoal?
- Type and amount of substance ingested implies significant potential toxicity
- Substance ingested known to be adsorbed by activated charcoal
- Less than 1 hour elapsed since ingestion
- No contraindications to administration of activated charcoal
Give 2 contraindications to administration of activated charcoal?
- Unprotected airway
- Gastrointestinal obstruction
What substances are known to NOT be effectively adsorbed by activated charcoal?
- Iron
- Lithium
- Potassium
- Toxic alcohols
- Pesticides
In drugs with which properties might multiple doses of activated charcoal administered enterally enhance elimination?
- Small volume of distribution
- Prolonged elimination half life
Why do multiple doses of activated charcoal administered enterally enhance elimination of drugs with a prolonged elimination half-life and small volume of distribution?
Theoretically, as a result of adsorption of the drug from the enteric circulation by charcoal in the intestinal lumen
Elimination of which drugs is improved with multiple doses of activated charcoal?
- Carbamazepine
- Dapsone
- Phenobarbital
- Quinine
- Theophylline
What is the limitation of the evidence base for activated charcoal?
Demonstration of efficacy is based on volunteer studies involving therapeutic drug ingestions, and studies demonstrating clinical benefit in poisoned patients remain limited
Is gastric lavage commonly used?
No - was once widespread practice, but now very rarely used
How is gastric lavage performed?
Large volumes of 0.9% saline are administered via a large bore nasogastric tube into the stomach, with recovery of gastric contents via the same route
Why is gastric lavage now very rarely used?
- Risk of aspiration
- Risk of fluid and electrolyte imbalance
- Lack of proven clinical benefit
How is induced emesis carried out?
Syrup of ipecac
Is induced emesis recommended in cases of poisoning?
No
Why is induced emesis no longer recommended?
- No clinical evidence that it is of benefit
- May reduce efficacy of activated charcoal
How is whole bowel irrigation carried out?
Prolonged administration of large volumes of osmotically-balanced polyethylene glycol with electrolytes
In drugs with what properties might whole bowel irrigation be of benefit?
Sustained released drug preparations
Why might whole bowel irrigation be of used following ingestion of sustained release drug preparations?
These drugs are formulated to exhibit delayed absorption, and so reducing transit time reduces the potential for drug absorption
What is the limitation of whole bowel irrigation?
There is little clinical evidence
When is whole bowel irrigation considered?
- Ingestion of toxic quantities of sustained release or enterically coated medications, especially when presentation is delayed
- Toxic quantities of iron preperations
Why is whole bowel irrigation considered in children who have ingested toxic quantities of iron preparations?
As there are few other strategies for reduction of absorption
How long should whole bowel irrigation be continued when used in poisoning?
Until rectal effluent is clear
What should be monitored during whole bowel irrigation therapy?
Fluid and electrolytes
How is urinary alkalisation achieved?
Administration of IV sodium bicarbonate
What is the purpose of urinary alkalisation?
Increase urinary pH to enhance excretion of certain drugs and toxic compounds
Drugs with which properties will have their excretion enhanced by urinary alkalisation?
- Really excreted
- Exist as weak acids
How does alkalisation of the urine aid the excretion of renally excreted drugs that exist as weak acids?
The alkaline urine favours the presence of the substance in its ionised form in the urine. The glomerulus filters both ionised and unionised forms, but only unionised molecules can be reabsorbed. As a result, ionised molecules are ‘trapped’ in the tubular lumen, enhancing excretion. This may also generate a concentration gradient facilitating further passage of the toxic substance into the urine
Give 5 drugs that urinary alkalisation increases the renal excretion of?
- Salicylate
- Phenobarbital
- Methotrexate
- Fluoride
- Chlorophenoxy herbicides
What is urinary alkalisation the standard therapy for?
Moderate to severe salicylate poisoning that does not meet the criteria for haemodialysis
What is IV lipid emulsion therapy a well accepted treatment for?
Local anaesthetic induced cardiovascular collapse
How does IV lipid emulsion therapy work in local anaesthetic-induced cardiovascular collapse?
It results in the creation of an enlarged intravascular lipid phase. This results in enhanced retention of the implicated drug within the lipid phase, preventing its toxic effect
What has been proposed as an additional use for IV lipid emulsion therapy?
May ameliorate the toxic effects of other lipid-soluble drugs
Give 2 examples of other lipid soluble drugs that IV lipid emulsion therapy may be useful in
- Beta blockers
- Calcium channel blockers
How strong is the evidence for IV lipid emulsion therapy in other lipid soluble drugs?
Clinical evidence is limited to case reports only
Give 13 drugs that have specific antidotes available for them
- Paracetamol
- Iron
- Opioids
- Ethylene glycol
- Methanol
- Digoxin
- Cyanide
- Warfarin
- Benzodiazepines
- Beta blockers
- Calcium channel antagonists
- Organophosphates
- Lead
What is the antidote for paracetamol?
N-acetylcysteine
What is the mechanism of N-acetylcysteine as an antidote to paracetamol?
Augments glutathione reserves and binds toxic metabolites
What is the antidote for iron?
Desferrioxamine
What is the mechanism of action of desferrioxamine as an antidote to iron?
Binds free iron and enhances renal elimination
What is the antidote to opioids?
Naloxone
What is the mechanism of action of naloxone as an antidote to opioids?
Competitive antagonist at the opioid receptor
What is the antidote for ethylene glycol?
Fomepizole or ethanol
What is the antidote for methanol?
Fomepizole or ethanol
What is the mechanism of action of fomepizole/ethanol as an antidote for ethylene glycol/methanol?
Competitive inhibitors of alcohol dehydrogenase preventing toxic metabolite production
What is the antidote for digoxin?
Digoxin-specific antibody fragments
What is the mechanism of action of digoxin-specific antibody fragments as an antidote for digoxin?
Binds digoxin, preventing interaction with target sites
What are the antidotes for cyanide?
- Hydroxycobalamin
- Dicobalt diedetate
- Sodium thiosulfate
What is the mechanism of action of hydroxycobalmin/dicobalt diedetate as an antidote for cyanide?
Cobalt compounds chelate cyanide - cobalt cyanides are less toxic than free cyanide
What is the mechanism of action of sodium thiosulfate as an antidote for cyanide?
Enhances endogenous cyanide elimination through sulfur donation
What is the antidote to warfarin?
Cryoprecipitate vitamin K
What is the mechanism of action of cryoprecipitate vitamin K as an antidote for warfarin?
Replaces vitamin K-dependent clotting factors
What is the antidote for benzodiazepines?
Flumazenil
What is the mechanism of action of flumazenil as an antidote to benzodiazepines?
It is a competitive antagonist at benzodiazepine receptor sites
What is the antidote for beta blockers?
Glucagon
What is the antidote for calcium channel antagonists?
Glucagon
What is the mechanism of action of glucagon as an antidote for beta blockers/calcium channel blockers?
Probably activates cardiac adenylate cyclase and increases intracellular cAMP, leading to positive inotropic and chronotropic effects
What is the antidote for organophosphates?
Pralidoxime
What is the mechanism of action of pralidoxime as an antidote for organophosphates?
Reactivates acetylcholinesterase
What is the antidote for lead?
Sodium calcium edetate
What is the mechanism of action of sodium calcium edetate as an antidote to lead?
Binds divalent and trivalent metal ions - calcium is displaced leading to formation of water soluble chelate
What has lead to a significant reduction in the incidence of childhood poisoning?
The introduction of child-resistant packaging
What is the purpose of child-resistant packaging?
Designed to be a significantly difficult as possible for young children to open, or gain access to the contents, within a reasonable time, and not difficult for adults to open
In addition to child-resistant packaging, what measures should be taken to prevent childhood poisoning?
- Safe storage
- Parental supervision
How is child resistance in packaging of medicines achieved?
By creating a barrier of either dexterity or cognition
Give an example of a barrier of dexterity that may be used in child-resistant packaging?
The need to undertake two physical actions at the same time, e.g. push down and turn cups on most medicine bottles
Give an example of a barrier of cognition that may be used in child-resistant packaging?
The need to understand an instruction, e.g. line up two arrows prior to attempting the opening manoeuvre
In the UK, what drugs are covered by legislation regarding child-resistant packaging?
- Aspirin
- Paracetamol
- Certain iron preparations
In the UK, what drugs are covered by legislation regarding child-resistant packaging?
- Aspirin
- Paracetamol
- Certain iron preparations
