Quinine toxicity

First a little bit of history. Quinine comes from the Cinchona tree, named as all good things are after a woman. The 2nd countess of Chinchon in Peru c.1742. The Quechua people of Peru used the bark of the Cinchona to prevent shivering by creating a mix of ground bark with a sweetened water thus producing tonic water. The Jesuits were the first to bing cinchona to Europe using it to treat malaria in Rome, this was in fact the first effective treatment against Plasmodium falciparum and the drug of choice until the 1940s when other drugs such as chloroquine emerged .

Quinine causes cinchonism (nausea, vomiting and tinnitus) in overdose but also blindness which is delayed and sometimes not noticed until the morning after the acute toxicity has resolved. Think of it as aspirin (the salicylism) that causes blindness.

Toxic Mechanism:

Class 1A antidysrhythmic with both sodium and potassium blocking properties thereby prolonging the QRS and QT intervals. In overdose it is toxic to the retina which can result in permanent blindness.

Toxicokinetics: 

• Rapid absorption with a 70% bioavailability
• Highly protein bound in adults but less so in the paediatric population (wherefore increased risk in children)
• Elimination half life is >24 hours in overdose and largely via hydroxylation with 20% being excreted in the urine unchanged.

Resuscitation:

• Seizures: IV benzodiazepines.
  • Check the patient is not in a dysrhythmia
  • Can be managed with benzodiazepines (varying doses in the textbooks, easy method is 0.1mg/kg IV for lorazepam (max 4mg) / midazolam (max 10mg) / diazepam (max 10mg). Or…
  • Lorazepam 0.1mg/kg max 4mg
  • Diazepam 0.15mg/kg max 10mg
  • Midazolam 0.2mg/kg max 10mg
• Coma: Urgent intubation and ventilation
• Wide-complex tachydyshythmias: Urgent serum alkalisation with sodium bicarbonate (aiming for QRS <100ms or a pH>7.45) followed by intubation and hyperventilation (aiming for a pH 7.5 – 7.55)
• Torsades de pointes:
  • Administer magnesium sulfate 10 mmol (0.05 mmol/kg in children) IV over 15 minutes.
  • Correct hypoxia, hypokalaemia and hypocalcaemia
  • If heart rate is <100 beats/minute commence an isoprenaline infusion IV at 1-10 microgram/min (0.05-1.0 microgram/kg/min in children) or overdrive pacing to maintain heart rate at 100-120 beats/minute.

Risk Assessment

• >1g usually produces some cinchonism
• Cardiotoxicity, CNS disturbance and blindness are commonly observed in doses over 5 grams and universal in doses over 10grams.
• Children: ingestion of 600mg (two tablets) in a child <6 years can potentially cause life-threatening toxicity.
• Clinical effects:
  • Cinchonism: Nausea, vomiting, tinnitus, vertigo and hearing loss. Resolves once blood quinine concentrations fall.
  • Cardiovascular: Hypotension, sinus tachycardia, QRS widening, prolongation of the PR and QT intervals. Wide-complex tachycardias and torsades de points. Usually occur within 8 hours of overdose and resolve once blood concentrations of quinine fall. These are mainly the effects you would expect with a drug that causes sodium and potassium channel blockade – ECG video link in resource section.
  • CNS: Drowsiness and confusion in larger ingestions. Coma and seizures are rare.
  • Eyes: Onset of visual disturbance is delayed, approximately 6 – 8 hours post ingestion. It is often not detected until the next morning. Complete blindness can occur in severe cases however, recovery of minor disturbances usually resolves over weeks.

Supportive Care

• IV fluids and antiemetics are required for cinchonism.
• If there is persistent hypoglycaemia consider using octreotide.
• If intubated see FASTHUGSINBED for further supportive care.

Investigations

• Screening: 12 lead ECG, BSL, Paracetamol level
• Specific:
  • Serial ECGs
  • EUC and formal visual field mapping
  • Quinine blood levels are generally not available in a clinically useful time.

Decontamination:

• 50g of activated charcoal maybe given to the alert and cooperative patient who has ingested any amount of quinine in overdose. An antiemetic maybe required to assist administration.
• CNS depression or seizures will require intubation to safely give charcoal via a nasogastric tube. This may need to be done pre-emptively if >5g of quinine has been consumed due to the risk of blindness.

Enhanced Elimination

• Multiple-dose activated charcoal is indicated in any patient who has ingested >5 g of quinine or who has any degree of visual disturbance.

Antidote

• None available.

Disposition

• Children who have ingested >600mg of quinine must be observed and monitored for 6 hours post ingestion. If asymptomatic with a normal ECG they are medically cleared.
• All patients with a deliberate overdose require 6 hours observation and cardiac monitoring. If asymptomatic with a normal ECG they are medically cleared.
• Patients with symptoms or an abnormal ECG will require monitoring until symptoms resolve.
• All patients with quinine toxicity require a careful assessment of visual fields and ophthalmological review
• Patients who develop a reduced GCS, seizures or an abnormal ECG within 6 hours require ICU admission

References and Additional Resources:

Additional Resources:

References:

• Boland ME, Roper SM, Henry JA. Complications of Quinine Poisoning. The Lancet 1985; 1(8425):384-385
• Guly U, Driscoll P. The management of quinine-induced blindness. Archives of Emergency Medicine 1992; 9:317-322
• Huston M, Levinson M. Are one or two dangerous? Quinine and quinidine exposures in toddlers. Journal of Emergency Medicine 2006; 31(4):395-401
• Langford NJ, Good AM, Laing WJ et al. Quinine intoxications reported to the Scottish Poisons Information Bureau 1997–2002: A continuing problem. British Journal of Clinical Pharmacology 2003; 56:576–578.