85. The treatment of the intoxicated patient: decontamination, facilitation of toxicant elimination, antidote administration, supportive treatment

Page created on November 30, 2019. Last updated on December 18, 2024 at 16:57

According to the lecturer the most important parts of this topic are the fascilitation of elimination and the antidotes.

Mechanisms of intoxications and poisoning-related death

The most important mechanisms intoxications can cause morbidity and death are:

• Respiratory failure
• Circulatory failure
• Systemic hypoxia
• Seizures
• Other organ damage
  • Liver
  • Lung

Poisoning-related respiratory failure:

This is usually due to overdose by CNS depressant drugs, like opioids, sedative hypnotics, ethanol, tricyclic antidepressants or antipsychotics.

Poisoning-related circulatory failure:

This can occur by a variety of mechanisms:

• Cardiac failure (asystole, arrhythmia)
  • Digitalis
  • Tricyclic antidepressants
  • Amphetamines
• Loss of vascular tone
  • Barbiturates
  • Tricyclic antidepressants
  • Antipsychotics
• Hypovolaemia
  • Iron (GI ulceration)
  • Anticoagulants
  • Arsenic (diarrhoea)

Systemic hypoxia:

This can occur due to one of two different mechanisms:

• Impaired O₂ transport
  • CO poisoning
  • Methaemoglobinaemia
    • Dapsone
    • Primaquine
• Impaired O₂ utilization
  • Cyanide

Seizures:

Seizures cause mortality indirectly, by inducing respiratory failure, aspiration, hyperthermia, lactic acidosis or rhabdomyolysis. Neuronal excitation lies in the background of seizures. This excitation can be caused by:

• Activation of excitatory receptors:
  • Muscarinic M1 receptors
    • Organophosphate insecticides
    • Nerve gases
  • NMDA glutamate receptors
    • Lithium
• Inhibition of inhibitory receptors
  • GABA_A receptors
    • Cocaine
    • Isoniazid
    • Tricyclic antidepressant
    • Cyclodiene insecticides
  • Glycine receptors
  • Adenosine A1 receptors
    • Theophylline
• Neuronal ATP depletion
  • Hypoxia
    • CO intoxication
  • Hypoglycaemia
    • Sulfonylureas
    • Insulin
  • Mitochondrial dysfunction
    • Cyanide

Symptoms of intoxication

Certain symptoms upon physical examination can clue you in on what the cause of the intoxication is.

Cardiovascular symptoms:

Symptom(s)	Causes
Hypertension	Sympathomimetics: Amphetamine and derivatives, cocaine, PCP
Hypotension	Vasomotor centre depressants: Barbiturates, opioids
	Sympatholytics: Beta blockers, α2-agonists
	Calcium channel blockers
	Tricyclic antidepressants
Tachycardia	Sympathomimetics: Amphetamine and derivatives, cocaine
	Anticholinergics
Bradycardia	Opioids
	Ethanol

Respiratory symptoms:

Symptom(s)	Causes
Tachypnoea	Centrally acting sympathomimetics: Amphetamine and derivatives
	Chemicals exciting the carotid body: Cyanide, CO
	Toxicants causing metabolic acidosis: Aspirin, isoniazid, methanol, ethylene glycol
Hypopnoea (shallow respiration)	Opioids
	α2-agonists

Temperature:

Symptom(s)	Causes
Hyperthermia	Centrally acting sympathomimetics: Amphetamine and derivatives
	Convulsive agents
	Anticholinergic drugs
	Uncoupling agents

Eye symptoms:

Symptom(s)	Causes
Miosis	Opioids
	α2-agonists
Mydriasis	Amphetamines
	Cocaine
	LSD
	Atropine
Nystagmus	Alcohol

External symptoms:

Symptom(s)	Causes
Sweaty skin	Parasympathomimetics: Organophosphates, nicotine.
	Amphetamines and derivatives
Dry skin	Parasympatholytics: Atropine, tricyclic antidepressants
Icterus	Paracetamol
Diarrhoea	Parasympathomimetics: Organophosphates

Laboratory and instrumental examinations

Anomaly	Causes
Increased anion gap metabolic acidosis	Aspirin, isoniazid, methanol, ethylene glycol
Increased osmolar gap	Ethanol, methanol, ethylene glycol
Hypokalaemia	K+-losing diuretics
	Theophylline
	β2 agonists
Hyperkalaemia	Beta blockers
	Digitalis
	Lithium
	RAAS inhibitors
Long QT	Antiarrhythmics Tricyclic antidepressants Antipsychotics Macrolides Fluoroquinolones

Emergency care of patient in coma

Upon meeting with a patient in coma of unknown origin, it’s important to try to think of likely causes. Immediately assessment and support of the airways, breathing and circulation come first, but the next step might depend on the etiology of the coma. The most likely causes are hypoglycaemia, hyperglycaemia, cardiac arrest, opioid overdose, ethanol overdose, hypoxaemia, etc.

If rapid blood glucose measurement is available, we can quickly rule in or out hypoglycaemia and hyperglycaemia. If no measurement is available, or the measurement shows hypoglycaemia, dextrose (D-glucose) should be given.

Bradypnoea and miosis can rule in opioid overdose, which is an indication for naloxone administration. Cardiac arrest is an indication for epinephrine. Convulsions is an indication for benzodiazepines.

Patients with suspected ethanol overdose should be given thiamine to prevent Wernicke encephalopathy. Any patient who receives dextrose should also receive thiamine, as giving dextrose to reverse hypoglycaemic coma in thiamine-deficient persons may induce Wernicke encephalopathy.

The standard “coma cocktail” includes those drugs which there are usually no risk in giving to patients with coma of unknown etiology.

• Dextrose (D-glucose)
• Naloxone
• Thiamine
• Oxygen

The important parts of the topic are below this line.

Decontamination of the intoxicated patient

Decontamination is important to prevent further drug absorption. Depending on whether the drug is being absorbed from the skin, stomach or bowels the approach to decontamination is different.

Decontamination of the skin:

To remove organophosphates from the skin we wash the skin with soapy water. The basic water causes hydrolysis of the organophosphate group, inactivating it.

To remove nicotine from the skin we rinse it with dilute acetic acid. This protonates the nicotine, causing it to become hydrophilic and therefore unable to be absorbed through the skin.

Decontamination of the stomach:

If the drug or toxicant source was ingested less than 1 hour ago, or if it is probable that undigested remains remain in the stomach, the stomach should be evacuated. This can be done by inducing emesis, by gastric lavage, by gastroscopy or even by gastrotomy. However, the value of stomach evacuation by these methods is debated as it’s uncertain whether it actually improves patient outcome.

Vomiting should not be induced if the toxic agent is convulsive, corrosive or has low surface tension. If vomiting is to be induced, so-called syrup of ipecac can be used. It contains active ingredients like emetine and cephaeline, which are serotonin agonists on 5-HT₄ receptors. They stimulate the vomiting reflex. It should be noted that syrup of ipecac isn’t really used anymore.

The best way to decontaminate the stomach is the use of activated charcoal. Activated charcoal is a form of carbon which is processed to have many small pores. This increases the surface area considerably. One gram of activated carbon has a surface area of more than 1000 m²! Activated charcoal adsorbs the poison, preventing it from being absorbed and instead causes it to be excreted with the faeces. Activated charcoal is ineffective against iron, lithium, ethanol, methanol, acid and base intoxication.

Other adsorbents for the use for stomach decontamination include:

• KMnO₄ (potassium permanganate) – for poisoning by nicotine or phosphides
• Fuller earth – for poisoning by paraquat (a herbicide)
• Soluble sulphates – for poisoning by barium

Decontamination of the bowels:

An important tool to decontaminate the bowels is whole bowel irrigation. It involves administration of large volumes of an isosmotic macrogol (polyethylene glycol) solution, which stimulates the washing out of the poison. Because the solution is isosmotic there is no net fluid or electrolyte movement across the mucosa, so whole bowel irrigation doesn’t cause volume depletion or electrolyte disturbances. 2 litres of solution should be administered per hour.

Activated charcoal decontaminated the bowels too and has replaced whole bowel irrigation in many cases. Whole bowel irrigation is used if the intestinal absorption of the toxicant is slow or if the toxicant is not adsorbed by activated charcoal.

Antidotes

Antidotes against drugs:

Drug	Antidote
Anticholinergics	Physostigmine
Benzodiazepines	Flumazenil
Beta blockers	Glucagon
Coumarins	Vitamin K + fresh frozen plasma/prothrombin concentrate
Digitalis glycosides	Digitalis antitoxin
Dabigatran	Idarucizumab
Fibrinolytics	Aminocaproic acid, tranexamic acid
Heparin	Protamine sulphate
Isoniazid	Pyridoxine (Vitamin B6)
Opioids	Naloxone
Paracetamol	N-acetylcysteine
Rivaroxaban, apixaban	Andexanet

Antidotes against metals (metal chelators):

Metal	Antidote (metal chelator)
Arsenic	Dimercaprol
Aluminium	Deferoxamine
Mercury	Dimercaprol or penicillamine
Copper	Penicillamine
Lead	Dimercaprol + penicillamine + EDTA
Iron	Deferoxamine

Antidotes against other toxicants:

Toxicant	Antidote
Carbon monoxide	O2, hyperbaric oxygen chamber
Cyanide	Hydroxocobalamin, amyl nitrite, sodium nitrite, sodium thiosulphate
Organophosphates (irreversible acetylcholinesterase inhibitors)	Atropine + pralidoxime + benzodiazepines
Methanol/ethylene glycol	Fomepizole/ethanol
Methaemoglobinaemia	Methylene blue

Methanol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase into formic acid, which is toxic to the retina. Ethanol and fomepizole are competitive ADH inhibitors, which prevents the formation of formic acid from methanol.

Ethylene glycol is metabolized by ADH and ALDH to metabolites which cause acidosis and renal tubular injury. Ethanol and fomepizole prevents the formation of these metabolites, too.

Enhancement of the redistribution of the toxicant

The only toxicant where enhancing the redistribution is beneficial is bupivacaine, a local anaesthetic. If this local anaesthetic is overdosed or injected into a vessel it exerts cardiotoxic effects and can cause cardiac arrest. Bupivacaine is lipophilic.

Intralipid is an emulsion of soy oil, originally indicated to be used as parenteral feeding. However, it was recently discovered that it may be useful in treating bupivacaine toxicity, and possibly the toxicity of other lipophilic drugs as well. The theory behind the detoxification is that the lipid droplets in intralipid “extract” the lipid-soluble bupivacaine from the cardiac muscle, thereby preventing it from causing cardiotoxic effects.

Enhancement of the elimination of the toxicant

We can divide these mechanisms into intracorporeal techniques, which enhance the physiological elimination of the drug by the liver or kidneys, and extracorporeal techniques, where the blood is channelled out of the body and removed by machines.

Intracorporeal techniques:

By administering sodium bicarbonate infusion, we can alkalinize the urine of the patient. This decreases the reabsorption of drugs which are weak organic acids, like salicylates, phenobarbital, isoniazid and certain herbicides.

Conversely, by administering ammonium chloride, we can acidify the urine of the patient. This decreases the reabsorption of drugs which are weak organic bases, like amantadine, memantine, quinidine and procainamide. However, this is not commonly used, as the urine is already slightly acidic and increasing its acidity would have limited effects.

Some drugs which are eliminated by excretion into the bile are reabsorbed in the intestines as part of the enterohepatic circulation. Non-absorbable adsorbents administered orally can bind to these drugs and prevent them from being reabsorbed, interrupting their enterohepatic circulation. The following adsorbents can be used:

• Activated charcoal
  • Carbamazepine
  • Phenobarbital
  • Dapsone
  • Quinine
  • Theophylline
• Cholestyramine
  • Digitoxin

Extracorporeal techniques:

Some drugs can be removed by haemodialysis, haemoperfusion and plasmapheresis:

• Haemodialysis
  • Methanol
  • Ethylene glycol
  • Salicylates
  • Metformin
• Haemoperfusion
  • Carbamazepine
  • Digitoxin
  • Theophylline
  • Phenobarbital
  • Valproate
• Plasmapheresis
  • Carbamazepine
  • Verapamil
  • Thyroxine

Supportive treatment

Supportive treatment involves monitoring the life functions of the patient and to correct any significant deviations from the normal.

Complication	Treatment
Ventricular tachycardia	Antiarrhythmic drugs, pacemaker
Hyperthermia	Cooling
Acidosis	Sodium bicarbonate infusion
Extreme bradycardia	Atropine, pacemaker
Hypotension	Fluid infusion, vasopressors
Convulsions	Benzodiazepines, barbiturates
Agitation	Benzodiazepines, haloperidol
Anuria	Furosemide, dialysis
Myoglobinuria	Sodium bicarbonate infusion, mannitol
Liver injury	Glucose + insulin
Paralytic ileus	Cholinomimetics + sympatholytics
Opioid-induced paralytic bladder	Catheterization (to prevent bladder rupture)