Other Overdose Flashcards
Patients who have taken poisons with delayed action should be admitted, even if they appear well. Delayed-action poisons include:
- Aspirin,
- Iron,
- Paracetamol,
- Tricyclic antidepressants, and
- co-phenotrope (diphenoxylate with atropine, Lomotil®);
- Modified-release preparations
It is often impossible to establish with certainty the identity of the poison and the size of the dose. This is not usually important because only a few poisons have specific antidotes; few patients require active removal of the poison. In most patients, treatment is directed at managing symptoms as they arise.
Explain how to treat changes in the following system:
- Respiration
- Blood pressure
- Heart
- Body temperature
- Convulsions
- Methaemoglobinaemia
Respiration:
- intubation and ventilation - respiratory acidosis (itu)
- Oxygen is not a substitute for adequate ventilation. It should be given in the highest concentration possible in poisoning with carbon monoxide and irritant gases
Blood pressure:
- CNS depressant - hypotension
- Systolic blood pressure <70mmHg = irreversible brain damage or renal tubular necrosis
- Raising the foot of the bed and admin of an infusion of either sodium chloride
- Vasoconstrictor sympathomimetics are rarely required and their use may be discussed with the NPIS.
- Hypertension (often transient) - sympathomimetic drugs such as amfetamines, phencyclidine, and cocaine.
Heart:
- Arrhythmias often respond to correction of underlying hypoxia, acidosis, or other biochemical abnormalities,
- Ventricular arrhythmias that cause serious hypotension require treatment.
Body temperature
- Hypothermia - common overdose with barbiturates or phenothiazines
- Hyperthermia - CNS stimulants
Convulsions
- Lasting <5min = No treatment
- Lorazepam or diazepam slow IV (not IM)
- Midazolam buccal/diazepam rectal
Methaemoglobinaemia:
- Treatment: Methylthioninium chloride
- Methaemoglobin concentration is 30% or higher, or if symptoms of tissue hypoxia are present despite oxygen therapy.
What is Methaemoglobinaemia?
Methaemoglobinaemia is the state of excessive methaemoglobin in the blood. methaemoglobin is an altered state of Hb where ferrous ions (Fe2+) of haem are oxidised to the ferric state (Fe3+) and rendered unable to bind O2. normal level is < 1.5%
Activate charcoal
- Activated charcoal - reduce the absorption and enhance the elimination of some drugs after they have been absorbed
- Mostly effective within 1 hour of ingestion
- Effective after 1 hour with antimuscarinics or modified-release
- Enhance the elimination of some drugs after absorption. Repeated doses are given after overdosage with:
- Carbamazepine
- Dapsone
- Phenobarbital
- Quinine
- Theophylline
- SHOULD NOT be used for poisoning with:
- petroleum distillates,
- corrosive substances,
- alcohols,
- malathion,
- cyanides and
- metal salts including iron and lithium salts.
Aspirin - BNF
The main features
- hyperventilation, tinnitus, deafness, vasodilatation, and sweating. Coma. The associated acid-base disturbances are complex.
Monitoring:
- plasma salicylate (repeated several hours), pH, and electrolytes can be measured;
- Clinical severity of poisoning is less below a plasma-salicylate concentration of 500 mg/litre (3.6 mmol/litre), unless there is evidence of metabolic acidosis.
Treatment:
- Activated charcoal can be given within 1 hour of ingesting more than 125 mg/kg of aspirin.
- Fluid losses should be replaced
- IV sodium bicarbonate (ensuring plasma-potassium concentration is within the reference range) to enhance urinary salicylate excretion (optimum urinary pH 7.5–8.5).Plasma-potassium concentration - corrected before giving sodium bicarbonate as hypokalaemia may complicate alkalinisation of the urine.
- Haemodialysis (severe salicylate poisoning/>700 mg/litre (5.1 mmol/litre)/presence of severe metabolic acidosis.
Theme: Overdose and poisoning: management
- A.N-acetylcysteine
- B.Urinary alkalinization
- C.Naloxone
- D.Haemodialysis
- E.Adrenaline
- F.Fomepizole
- G.Glucagon
- H.IV bicarbonate
- I.Flumazenil
- J.Desferrioxamine
For each of the following scenarios please select the most appropriate treatment:
- A man is admitted following an aspirin overdose. He is unwell with pulmonary oedema and a severe metabolic acidosis.
Haemodialysis - Both pulmonary oedema and metabolic acidosis are indications for haemodialysis in salicylate overdose.
A 36-year-old male was admitted urgently to hospital 45-minutes after taking 50 regular-strength (75mg) aspirin tablets. He has a background of previous self-harm attempts with several admissions due to intentional overdose. His past medical history consisted of anxiety and depression.
On admission, he had increased respiratory of 25 breaths per minute, blood pressure of 111/77 mmHg and heart rate of 110 beats per minute. He was sweating profusely with a temperature of 38.1ºC.
What is the most appropriate initial management?
- Activated charcoal
- Haemodialysis
- Intravenous bicarbonate
- Intravenous fluids
- Intravenous paracetamol
Activated charcoal can be used within an hour of an aspirin overdose
Important for meLess important
Salicylate poisoning can result in severe morbidity and mortality. Initial treatment of overdose involves resuscitation which would be to maintain his adequate airway and adequate circulation.
Activated charcoal administration helps to achieve gastric decontamination by adsorbing the salicylate in the gastrointestinal tract. Initial treatment should include the use of oral activated charcoal, especially if the patient presents within 1-hour of ingestion.
Intravenous fluids are part of the initial resuscitation for overdose management particularly if the patient is hypotensive. In this situation, given the patient has presented within 1-hour it would be vital to get activated charcoal administered as soon as possible.
Intravenous paracetamol would be avoided particularly if there is an unclear history of the overdose or suspicions of a mixed overdose within which paracetamol ingestion is common.
Intravenous sodium bicarbonate is given in cases of significant aspirin overdose where the salicylate level greater than 35 mg/dL 6-hours after ingestion regardless of what the serum pH shows, as this promotes the elimination of aspirin in the urine. In such situations like this where the presentation is acute and a level is not yet available, activated charcoal would remain first-line management.
Haemodialysis can enhance the removal of salicylate from the blood in severe poisoning. Such conditions include people with high salicylate blood levels; significant neurotoxicity with features of agitation, coma, convulsions; kidney failure, pulmonary oedema, or cardiovascular instability.
Discuss (2)Improve
A 28-year-old woman is brought to the emergency department by her friend. The patient does not engage with you, however, the friend states that the patient had an argument with her partner 3 hours ago and has since taken at least 6 full packets of aspirin, reportedly with the intention of ending her life. This is not the first time the patient has displayed suicidal ideation.
In addition to other investigations, a venous blood gas is taken at presentation, and also at 12 hours following presentation.
Which pattern of acid-base abnormalities would be present in this patient at presentation (t=0), and after 12 hours (t=12)?
t=0: metabolic acidosis, t=12: metabolic acidosis
- t=0: metabolic acidosis, t=12: respiratory alkalosis
- t=0: respiratory acidosis, t=12: metabolic alkalosis
- t=0: respiratory alkalosis, t=12: metabolic acidosis
- t=0: respiratory alkalosis, t=12: respiratory alkalosis
t=0: respiratory alkalosis, t=12: metabolic acidosis
Salicylate poisoning first causes respiratory alkalosis
Important for meLess important
This patient is likely to be suffering from aspirin (salicylate) poisoning. Firstly, it is important in potential overdose patients that the clinician considers that the patient may have consumed a greater quantity of aspirin than reported. They may have also consumed other substances in addition to aspirin. Broad toxicological workup including a salicylate level, paracetamol level, and urine toxicological screen would be required, in addition to standard care.
An overdose of salicylates such as aspirin first causes respiratory alkalosis, followed by metabolic acidosis. This is due to a biphasic response to salicylate ingestion. Salicylates initially stimulate the CNS respiratory center, causing tachypnoea and leading to a fall in PaCO2 and a respiratory alkalosis.
An anion gap metabolic acidosis then follows, due primarily to the accumulation of organic acids, including lactic acid and ketoacids, as well as metabolites of aspirin which are weak acids. The timeframe for this change is not definitive, however, 12 hours would be considered an adequate time for this shift to occur.
Discuss (1)Improve
An 18-year-old girl is brought into the emergency department because of a history of cough, and breathing difficulty. She had experienced multiple episodes of vomiting in the last few hours and is also complaining of ringing in her ears. Her mum said she was found with a few empty packets of aspirin in her hand. Some of her blood tests can be found below.
- Na+ 148mmol/L(135 - 145)
- K+ 6.0mmol/L(3.5 - 5.0)
- Urea1 4.1mmol/L(2.0 - 7.0)
- Creatinine 241µmol/L(55 - 120)
- eGFR 39ml/min/1.73m2(>89ml/min/1.73m2)
- Salicylate levels 646mg/l(<300mg/l)
From the history above, what would you most likely expect to find on her arterial blood gas sample?
- Metabolic acidosis only
- Metabolic alkalosis only
- Mixed respiratory acidosis and metabolic alkalosis
- Mixed respiratory alkalosis and metabolic acidosis
- Respiratory acidosis only
Mixed respiratory alkalosis and metabolic acidosis.Salicylate overdose can cause a mixed primary respiratory alkalosis and metabolic acidosis
- Salicylate overdose usually causes mixed respiratory alkalosis and metabolic acidosis. Direct stimulation of the cerebral medulla causes hyperventilation and respiratory alkalosis. As aspirin is metabolized, it inhibits ATP synthesis by uncoupling oxidative phosphorylation in the mitochondria. Lactate levels then increase due to the increase in anaerobic metabolism. The lactic acid along with a slight contribution from the salicylate metabolites result in metabolic acidosis.
- DKA, severe diarrhoea and renal failure often cause metabolic acidosis.
- Vomiting, nasogastric suctioning, hypokalemia, and antacid use often cause metabolic alkalosis.
- COPD, obesity, pneumonia, respiratory muscle weakness can often cause respiratory acidosis.
- Hyperventilation, anaemia, or respiratory centre stimulation from drugs can cause respiratory alkalosis. This is the case here but also causes metabolic acidosis.
Overview:
- A key concept for the exam is to understand that salicylate overdose leads to a mixed respiratory alkalosis and metabolic acidosis. Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis. In children metabolic acidosis tends to predominate.
Features
- hyperventilation (centrally stimulates respiration)
- tinnitus
- lethargy
- sweating, pyrexia*
- nausea/vomiting
- hyperglycaemia and hypoglycaemia
- seizures
- coma
Treatment
- general (ABC, charcoal)
- urinary alkalinization with intravenous sodium bicarbonate - enhances elimination of aspirin in the urine
- haemodialysis
Indications for haemodialysis in salicylate overdose
- serum concentration > 700mg/L
- metabolic acidosis resistant to treatment
- acute renal failure
- pulmonary oedema
- seizures
- coma
*salicylates cause the uncoupling of oxidative phosphorylation leading to decreased adenosine triphosphate production, increased oxygen consumption and increased carbon dioxide and heat production
Opioid - BNF
Symptoms
- coma, respiratory depression, and pinpoint pupils.
Naloxone has a shorter duration of action than many opioids, close monitoring and repeated injections are necessary according to the respiratory rate and depth of coma.
When repeated administration of naloxone is required, it can be given by continuous intravenous infusion instead and the rate of infusion adjusted according to vital signs.
The effects of some opioids, such as buprenorphine, are only partially reversed by naloxone.
Methadone (long durations of action) - monitored for long periods following large overdoses.
A 25-year-old male is brought to the emergency department after being found lying unconscious on the pavement. A syringe and a used pack of oxycodone and alprazolam were also found next to him.
On examination, he is drowsy with bilateral pupil constriction noted. His bowel sounds are decreased and fresh needle marks are noted on his right arm.
His observations are: blood pressure 110/70 mmHg, heart rate 55/min, oxygen saturation of 95% on room air and temperature 36ºC, and respiratory rate of 5 breaths per minute.
Blood glucose level: 8 mmol/L
Which one of the following is the most appropriate management?
- Flumazenil
- Midazolam
- Adrenaline
- Insulin
- Naloxone
Opiate - naloxone
Important for meLess important
This patient has the typical signs of acute opioid toxicity with bradypnoea, miosis and altered mental status. Naloxone is administered to patients with suspected opiate overdose, with the main aim of restoring adequate ventilation. In apnoeic patients, ventilation and oxygenation with a bag-valve mask is recommended to decrease the risk of acute lung injury in hypercapnoeic subjects.
Most cases of benzodiazepine overdose are managed expectantly with supportive care. Flumazenil is a competitive antagonist of the benzodiazepine receptor and its use is usually reserved for iatrogenic cases (e.g. sedation following general anaesthesia). Flumazenil can precipitate withdrawal seizures in patients with chronic benzodiazepine use and is therefore contraindicated in this patient group.
Reference:
Mills CA, Flacke JW, Flacke WE, Bloor BC, Liu MD. Narcotic reversal in hypercapnic dogs: comparison of naloxone and nalbuphine. Can J Anaesth. 1990;37(2):238.
Discuss (6)Improve
A 65-year-old man is on the surgical ward. He underwent a laparotomy for small bowel obstruction yesterday. He is on patient controlled analgesia with morphine. The nurses report that he has a decreased conscious level and respiratory rate of 4 breaths per minute. On attending the patient he suffers a respiratory arrest. You initiate bag mask ventilation.
What treatment should he receive?
- 40 microgram increments of naloxone titrated to effect
- 300 micrograms of flumazenil
- Defibrillation
- 400 microgram bolus of naloxone
- Intubation and ventilation
400 microgram bolus of naloxone
This patient has suffered a respiratory arrest likely due to opioid toxicity. Therefore a 400 microgram bolus of naloxone should be administered. It is important to remember that naloxone has a short half life and therefore further naloxone will likely be required.
Theme: Overdose and poisoning: management
- A.N-acetylcysteine
- B.Urinary alkalinization
- C.Naloxone
- D.Haemodialysis
- E.Adrenaline
- F.Fomepizole
- G.Glucagon
- H.IV bicarbonate
- I.Flumazenil
- J.Desferrioxamine
For each of the following scenarios please select the most appropriate treatment:
- 3.A 24-year-old intravenous drug user presents with a respiratory rate of 6 / minute. He has pin-point pupils.
Naloxone
Iron overdose
Desferrioxamine mesilate, which chelates iron.
The serum-iron concentration is measured as an emergency and IV desferrioxamine mesilate given to chelate absorbed iron in excess of the expected iron binding capacity.
In severe toxicity intravenous desferrioxamine mesilate should be given immediately without waiting for the result of the serum-iron measurement.
TCA or related medicine - BNF
Symptoms:
dry mouth, coma of varying degree, hypotension, hypothermia, hyperreflexia, extensor plantar responses, convulsions, respiratory failure, cardiac conduction defects, and arrhythmias. Dilated pupils and urinary retention also occur. Metabolic acidosis may complicate severe poisoning; delirium with confusion, agitation, and visual and auditory hallucinations are common during recovery.
Supportive measures:
- IV lorazepam or IV diazepam - to treat convulsions.
- Activated charcoal - within 1h.
- Arrhythmias - correction of hypoxia and acidosis. The use of anti-arrhythmic drugs is best avoided, but IV infusion of sodium bicarbonate can arrest arrhythmias or prevent them in those with an extended QRS duration.
- Diazepam (oral) - sedate delirious patients
An 81-year-old woman is brought into the emergency department by her daughter following an unwitnessed collapse. The patient is confused so there is no obtainable history. Her past medical history includes depression, Alzheimer’s dementia, and atrial fibrillation. Her regular medications include bisoprolol, donepezil, and amitriptyline. It was noted by the ambulance crew that she had taken an excess of her regular medications.
On examination, the chest is clear and saturations are 96% on room air. An ECG demonstrates a sinus rhythm with a rate of 34/min. The blood pressure is 94/59mmHg. Her Glasgow coma score is 13/15. She is afebrile and the blood sugar is 7.8mmol/L.
What is the most appropriate initial treatment?
- Atropine
- Ephedrine
- Glucagon
- IV bicarbonate
- Metaraminol
Beta-blocker - atropine, glucagon in resistant cases
Important for meLess important
This woman is suffering from a beta-blocker overdose for which the management aims to restore a normal heart rate. The first line in these cases is atropine which is, therefore, the correct answer here.
Ephedrine is both an alpha- and beta-adrenergic receptor agonist and therefore exerts a positively chronotropic effect on the heart as well as acting as a vasopressor. This is predominantly used in anaesthesia and requires invasive monitoring. Atropine is the preferred first-line agent in cases of beta-blocker overdose.
Glucagon can be used to manage beta-blocker overdose however is usually used as a second-line agent in cases that are resistant to atropine.
IV bicarbonate is an agent used for a tricyclic antidepressant (TCA) overdose, however, this is not the case here as TCA overdoses result in tachycardia rather than bradycardia.
Metaraminol is a selective alpha-adrenergic agonist and is used for vasopressor support. Unfortunately, this would have minimal impact in normalising this woman’s heart rate and reversing the effects of the beta-blocker.
A 34-year-old man with a history of depression is admitted to the Emergency Department. He states he has taken an overdose of both diazepam and dosulepin. On examination blood pressure is 116/78 and the pulse is 140 bpm. His respiratory rate is 8 per minute and the oxygen saturations are 97% on room air. What is the most appropriate next course of action?
- Give flumazenil
- Insert a haemodialysis line
- Obtain an ECG
- Give naloxone
- Start N-acetylcysteine infusion
As this patient has a marked tachycardia the first step would be to obtain an ECG. If changes such as QRS widening are seen then intravenous bicarbonate should be given
Some users have argued that an ‘ABC’ approach should be taken, with flumazenil given to reverse the respiratory depression. The potential risk of doing this would be inducing a seizure given the coexistent tricyclic overdose
Overview:
Overdose of tricyclic antidepressants is a common presentation to emergency departments. Amitriptyline and dosulepin (dothiepin) are particularly dangerous in overdose. Early features relate to anticholinergic properties: dry mouth, dilated pupils, agitation, sinus tachycardia, blurred vision.
Features of severe poisoning include:
- arrhythmias
- seizures
- metabolic acidosis
- coma
ECG changes include:
- sinus tachycardia
- widening of QRS
- prolongation of QT interval
Widening of QRS > 100ms is associated with an increased risk of seizures whilst QRS > 160ms is associated with ventricular arrhythmias
Management:
- IV bicarbonate
- first-line therapy for hypotension or arrhythmias
- indications include widening of the QRS interval >100 msec or a ventricular arrhythmia
- other drugs for arrhythmias
- class 1a (e.g. Quinidine) and class Ic antiarrhythmics (e.g. Flecainide) are contraindicated as they prolong depolarisation
- class III drugs such as amiodarone should also be avoided as they prolong the QT interval
- response to lignocaine is variable and it should be emphasized that correction of acidosis is the first line in the management of tricyclic induced arrhythmias
- intravenous lipid emulsion is increasingly used to bind free drug and reduce toxicity
- dialysis is ineffective in removing tricyclics
