Sodium Valproate poisoning


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

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    Key Points

    1. Toxicity is dose-dependent and serious symptoms are unlikely with an ingestion less than 400mg/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 (e.g. Enhanced elimination with haemodialysis)

    For 24 hour advice, contact Victorian Poisons Information Centre 131126

    Background

    Symptom onset is usually within 4 hours for standard release preparations and up to 8 to 13 hours following sustained-release or enteric-coated formulations.

    Clinical features include nausea, vomiting, drowsiness, ataxia, seizures, coma and life-threatening arrhythmias. Monitoring of drug concentrations can be helpful, particularly if the case of larger ingestions. Bone marrow suppression may occur after 3 to 5 days after massive ingestion.

    Children requiring assessment

    All children with deliberate self-poisoning or significant (> 100mg/kg OR 50 mg/kg more than the child’s usual single therapeutic dose) accidental ingestion
    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
    • Presented as syrup, immediate or modified- release tablets or capsules
    • If possible determine the exact name and tablet size.
    • Calculate the maximum possible dose per kg

    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 — severe toxicity
    • > 1000 mg/kg — coma, multi-organ failure, cerebral oedema, potentially life-threatening

    Co-ingestants e.g. paracetamol

    Examination:

    • CNS
      • Drowsiness, ataxia, seizures, coma
    • GIT
      • Nausea, vomiting, abdominal pain
    • CVS
      • 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.)

    Consider the possibility of co ingestions, either accidental or deliberate

    Investigations:

    ECG: initially and repeat at 6 hours until normal.  

    Sodium valproate serum concentration (in children with ingestion of > 200mg/kg, unknown amount or significant symptoms)

    Toxic concentration

    • 350 to 700 micromol/L (50 to 100 mg/L or micrograms/mL) – therapeutic range
    • > 6000 micromol/L (850 mg/L) - associated with severe poisoning

    Blood glucose concentration

    Paracetamol concentration in all intentional overdoses

    Acute Management

    Children Requiring Treatment

    • All symptomatic children
    • Acute ingestion of unknown quantity
    • Based on ingestion amount:
      • Sodium valproate ingestion of > 100 mg/kg OR 50 mg/kg more than the child’s usual single therapeutic dose if the child is on maintenance sodium valproate treatment

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

    Resuscitation

    • Standard procedures and supportive care

    Decontamination 

    • This should be in discussion with a toxicologist (call the Poisons Information Centre 13 11 26)
    • Consider charcoal if massive ingestion (>400mg/kg ingested) and presentation within  4 hours of ingestion
    • Enhanced elimination (e.g.. haemodialysis) is considered in life-threatening poisoning – ingestions >1g/kg or concentrations >6000 micromol/L

    Mild symptoms (e.g. ataxia, GIT symptoms)

    • Observe 6 hours if ingestion of immediate-release preparation or 12 hours if ingestion of sustained-release preparation
    • Discharge if symptom-free

    Moderate-to-severe or persistent symptoms after 6 hours of observation OR ingestions > 400mg/kg (e.g. 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 and serial drug concentration monitoring should be discussed with a toxicologist.

    When to admit/consult local paediatric team, or who/when to phone:

    Admission should be considered for all children and young people with an intentional overdose or in children with persisting symptoms after 6 hours observation.

    If ingestion of >1g/kg sodium valproate or valproate serum concentrations > 6000 micomol/L, the child should be transferred to an intensive care unit with dialysis facilities.

    Consult Contact Victorian Poisons Information Centre 131126 for advice

    When to consider transfer to a tertiary centre:

    Children with severe symptoms with the potential to require intensive care review

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

    Discharge Criteria:

    Normal GCS

    Normal ECG

    Period of observation as above

    For deliberate ingestion a risk assessment should indicate that the child is at low risk of further self-harm in the discharge setting

    Discharge information and follow-up:

    Poisoning prevention for children Parent information

    Victorian Poisons Information Centre: 13 11 26 www.austin.org.au/poisons

    Intentional self –harm: Referral to local mental health services e.g. Orygen Youth Health: 1800 888 320 

    Recreational poisoning: Referral to YoDAA, Victoria's Youth Drug and Alcohol Advice service: 1800 458 685

     

    Last updated January 2018