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Sodium valproate poisoning


  • Statewide logo

    This guideline has been adapted for statewide use with the support of the Victorian Paediatric Clinical Network

  • See also 

    Poisoning - acute guidelines for initial management
    Resuscitation

    Key Points

    1. Toxicity is dose-dependent and serious symptoms are unlikely with ingestions <400 mg/kg
    2. Sodium valproate concentrations and an ECG can be helpful in assessment
    3. Early consideration of transfer to a tertiary centre due to need for intensive care support (eg Enhanced elimination with haemodialysis)

    For 24 hour advice, contact the Poisons Information Centre 13 11 26

    Background

    • Symptom onset is usually within 4 hours for standard release preparations, and up to 13 hours following enteric-coated formulations
    • Monitoring of drug concentrations can be helpful, particularly in the case of larger ingestions
    • Bone marrow suppression may occur 3 to 5 days after massive ingestion

    Children requiring assessment

    • All children with deliberate self-poisoning or significant accidental ingestion (>50 mg/kg OR 50 mg/kg more than the child’s usual single therapeutic dose)
    • Any symptomatic child
    • Acute ingestion of unknown quantity
    • Any child where the developmental age is inconsistent with accidental poisoning as non-accidental poisoning should be considered

    Risk assessment

    History

    • Intentional overdose or accidental
    • Dose:
      • Stated or likely dose taken
      • Ingested as syrup, immediate or enteric coated tablets
      • If possible, determine the exact name and tablet size
      • Calculate the maximum possible dose per kg
    • Consider the possibility of co-ingestants (eg paracetamol), either accidental or deliberate  
    Sodium valproate dose response relationship:
    • <200 mg/kg — unlikely to develop more than mild sedation
    • 200 to 400 mg/kg — moderate toxicity with CNS depression
    • >400 mg/kg — risk of multi-organ system toxicities
    • >1000 mg/kg — coma, multi-organ failure, cerebral oedema, potentially life-threatening

    Examination

    • Central nervous system: drowsiness, ataxia, seizures, coma
    • Gastrointestinal: nausea, vomiting, abdominal pain
    • Cardiovascular: hypotension, arrhythmias (QT prolongation), tachycardia
    • Metabolic: hypernatraemia, elevated, lactate, metabolic acidosis, hypocalcaemia, hypoglycaemia, hyperammonaemia, deranged liver function tests
    • Myelosuppression – late onset

    Always check for Medicalert bracelet in any unconscious patient, or any other signs of underlying medical condition (fingerprick marks etc.)

    Investigations

    • ECG: initially and repeat at 6 hours until normal
    • Sodium valproate serum concentration:
      • Therapeutic range (total valproic acid concentration): 350 to 700 micromol/L (50 to 100 mg/L or micrograms/mL)
      • >6000 micromol/L (850 mg/L) is associated with severe poisoning
    • Blood glucose concentration
    • Electrolytes, liver function test, blood gas, ammonia, calcium
    • Paracetamol concentration in all intentional overdoses

    Acute Management

    All cases of ingestions >400 mg/kg should be discussed with a toxicologist early in regard to decontamination

    1. Resuscitation

    • Supportive treatment to maintain adequate blood pressure and electrolyte balance is essential
    • IV fluid resuscitation 20 mL/kg for hypovolaemia or hypotension
    • Potassium and glucose administration as necessary

    2. Decontamination

    • This should be in discussion with a toxicologist
    • Consider charcoal if large ingestion (>400 mg/kg ingested) and presentation within 4 hours of ingestion
    • Enhanced elimination (eg haemodialysis) is considered in life-threatening poisoning – ingestions >1 g/kg or drug concentrations >6000 micromol/L

    Ongoing care and monitoring

    Mild symptoms
    (eg Ataxia, gastrointestinal symptoms)

    • Observe for 6 hours if ingestion of immediate-release preparation or minimum of 12 hours if ingestion of enteric coated preparation
    • Discharge if symptom-free

    Moderate-to-severe or persistent symptoms after 6 hours of observation OR ingestions >400 mg/kg
    (eg Depressed conscious state or cardiac arrhythmias)

    • Admit for observation and supportive management in a tertiary centre
    • Serum sodium valproate concentration should be performed at 6 hours
    • If ongoing symptoms, serial drug concentration monitoring should be discussed with a toxicologist

    Consider consultation with local paediatric team when

    • Any child or young person presents with intentional overdose as admission should be considered
    • Children have persisting symptoms after 6 hours observation

    Consult the Poisons Information Centre 13 11 26 for advice

    Consider transfer when

    • A child has ingested >1 g/kg sodium valproate or valproate serum concentrations >6000 micromol/L
      • the child should be transferred to an intensive care unit with dialysis facilities
    • A child has severe symptoms with the potential to require intensive care review or care required is beyond the comfort level of the current hospital 

    For emergency advice and paediatric or neonatal ICU transfers, call the Paediatric Infant Perinatal Emergency Retrieval (PIPER) Service: 1300 137 650

    Consider discharge when

    • Normal GCS
    • Normal ECG
    • Period of observation as above

    Assessing risk and connecting to community services

    • Prior to discharge, adolescents who present with deliberate ingestions need a risk assessment regarding the likelihood of further ingestions or other attempts to self-harm
    • Assessment of other drug and alcohol use should also be undertaken
    • If, after risk assessment, it is deemed safe to discharge a patient from hospital, but ongoing mental health or drug and alcohol needs are identified, the adolescent should be linked with appropriate services (see links below for services in the State of Victoria)

     Discharge information and follow-up

    Parent Information: Poisoning prevention for children
    Prevention of poisoning (Victorian Poisons Information Centre)

    Poisons Information Centre: phone 13 11 26


    Victoria

    Poisons Information Centre

    Child & Adolescent Mental Health Services (CAMHS): Victorian government mental health services are region-based

    Orygen Youth Health: Specialist mental health services for people aged 15–25 years, residing in the western and north-western regions of metropolitan Melbourne. Triage/intake - 1800 888 320.

    Headspace: National Youth Mental Health Foundation with local headspace centres

    YSAS (Youth Support and Advocacy Service): Outreach teams across Melbourne and regional Victoria for young people experiencing significant problems with alcohol and/or drug use

    YoDAA: Victoria’s Youth Drug and Alcohol Advice service - provides information and support for youth AOD needs or anyone concerned about a young person

    Infoxchange Service Seeker: Search for local community support services eg local doctor, dentist, counselling services, drug and alcohol services

    Last updated October 2020

  • Reference List

    1. IBM Micromedex 2019, Sodium valproate, viewed November 2019, <http://www.micromedexsolutions.com.acs.hcn.com.au/micromedex2/librarian?acc=36265>
    2. National Poisons Centre New Zealand 2019, Sodium Valproate, TOXINZ™ Poisons Information, viewed November 2019, <https://www.toxinz.com/Demo/11/TjAzQUcwMWI%3D>