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SIADH

     By Hiren Divecha
                  FY2
    Hairmyres Hospital
            1/5/2007
Sodium
• Needed for:
  1. Nerve conduction
  2. Co-transport of metabolites
• 135-146 mmol/L
• Regulation
  –   Thirst
  –   ADH
  –   RAAS
  –   ANP & BNP
Euvolaemic




                Hyponatraemia




Hypervolaemic                   Hypovolaemic
Hypovolaemic           Euvolaemic             Hypervolaemic
Extracellular Na   ↓                      N                      ↑
TBW                Slightly ↓             Slightly ↑             ↑↑
Causes             Renal                  Thiazides              CCF
                   •Diuretics
                   •Osmotic diuresis      SIADH                  Liver failure
                   (glucose, urea,
                   mannitol)              Glucocorticoid def     Renal failure
                   •Addison’s
                   •Salt-wasting neph     Hypothyroidism         Nephrotic
                                                                 syndrome
                   Gut                    Primary polydipsia
                   •Vomiting                                     Pregnancy
                   •Diarrhoea             iv dextrose

                   Other                  Sodium-free irrigant
                   •Haemorrhage
                   •3rd space loss (BO,
                   burns, peritonitis,
                   pancreatitis)
Causes of SIADH
Neoplastic      Pulmonary         CNS           Drugs              Other
Lung          Infection           Infection     AVP analogues      Idiopathic
•Small cell   •Pneumonia          •Abscess      •Desmopressin
•Mesothelioma •Abscess            •Meningitis   •Oxytocin          Hereditary
              •TB                 •AIDS         •Vasopressin       (V2 receptor)
GI            •Aspergillosis
•Stomach                          Bleeds        Stimulate AVP
•Pancreas     Asthma              •Subdural     release/action
                                  •SAH          •SSRIs
GU              Cystic Fibrosis                 •Antipsychotics
•Bladder                          CVA           •Anti-epileptics
•Prostate       PPV                             •NSAIDs
•Endometrium                      Head trauma   •MDMA

Thymoma                           MS, GBS
Leukaemia
Lymphoma                          Shy-Drager
Sarcoma
Clinical Features
<120 mmol/l             <110 mmol/l
– Dysgeusia             • Drowsiness
– Lethargy              • Confusion
– Anorexia              • Depressed reflexes
– Nausea, vomiting      • Extensor plantar responses
– Irritability          • Seizures
– Headache              • Coma
– Cramps                • Death
– Muscle weakness
Criteria for SIADH
• Bartter and Schwartz (1967)
  – Hyponatraemia
  – Clinically euvolaemic
  – No diuretic use
  – Serum osmolality <275mOsm/kg
  – Urine osmolality >100 mOsm/kg
  – Urine sodium >40mmol/L
  – Normal thyroid, adrenal and renal function
Management - acute
• Benzodiapines
• Aim for 1-2mmol/L/hr initially
  – Resolution of neurology
  – Slow replacement (10 mmol/L/day)
• Frusemide (free water excretion)
• Find and treat cause
TBW = weight * 0.5 (girls)
    = weight * 0.6 (guys)

Na+ to replace = desired change in Na+ * TBW

Rate of Na+ replacement =
                 rate of desired change * TBW

Rate infusion =
   Rate of Na+ replacement / (conc of infusate)
As a rough guide
• To increase Na+ by 1mmol/L/hr
  – 1 ml/kg/hr of 3% saline
  – 1.7 ml/kg/hr of 1.8% saline


• Max. rate = 70 mmol of Na+/hr

• Monitor U&E 2 – 3 hourly
Management - Chronic
• Risk of osmotic demyelination if change is
  >12mmol/L/day
• Symptomatic
  – Aim for lower rate of correction (0.5mmol/L/hr)
• Asymptomatic
  – Fluid restrict
  – Demeclocycline
  – Oral urea
Fluid restriction
       (Urinary Na + Urinary K) / Plasma Na
• >1
  – <500ml/day
• 1
  – 500-700ml/day
• <1
  – <1L/day
Vasopressin Receptor Antagonists
• RCTs showed sustained increase in plasma Na
  compared to placebo
• Risk of hypotension with non-selective
  antagonists
• V2 selective antagonists in trials
• No reports of osmotic demyelination
Osmotic Demyelination Syndrome
• Central pontine + extrapontine
• Over-enthusiastic correction of Na+
• In chronic hyponatraemia
  – Brain tissue losses inorganic and organic solutes
  – Takes few days
• Predisposing factors
  – Alcoholism
  – Malnourishment
Osmotic Demyelination Syndrome
• Demyelination
• Pontine symptoms
  – Dysarthria, dysphagia, pseudobulbar palsy
  – Flaccid quaraparesis
• Extra-pontine
  – Tremor, ataxia, mutism
  – Parkinsonism, dystonia
• Reversible ?
  – 5% dextrose and desmopressin
SIADH
References
1. “The syndrome of inappropriate
   antidiuresis”, Ellison et al, NEJM,
   2007;356(20):2064-72
2. “Hyponatraemia”, Adrogue & Madias, NEJM,
   2000;342(21):1581-89

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SIADH

  • 1. SIADH By Hiren Divecha FY2 Hairmyres Hospital 1/5/2007
  • 2. Sodium • Needed for: 1. Nerve conduction 2. Co-transport of metabolites • 135-146 mmol/L • Regulation – Thirst – ADH – RAAS – ANP & BNP
  • 3. Euvolaemic Hyponatraemia Hypervolaemic Hypovolaemic
  • 4. Hypovolaemic Euvolaemic Hypervolaemic Extracellular Na ↓ N ↑ TBW Slightly ↓ Slightly ↑ ↑↑ Causes Renal Thiazides CCF •Diuretics •Osmotic diuresis SIADH Liver failure (glucose, urea, mannitol) Glucocorticoid def Renal failure •Addison’s •Salt-wasting neph Hypothyroidism Nephrotic syndrome Gut Primary polydipsia •Vomiting Pregnancy •Diarrhoea iv dextrose Other Sodium-free irrigant •Haemorrhage •3rd space loss (BO, burns, peritonitis, pancreatitis)
  • 5. Causes of SIADH Neoplastic Pulmonary CNS Drugs Other Lung Infection Infection AVP analogues Idiopathic •Small cell •Pneumonia •Abscess •Desmopressin •Mesothelioma •Abscess •Meningitis •Oxytocin Hereditary •TB •AIDS •Vasopressin (V2 receptor) GI •Aspergillosis •Stomach Bleeds Stimulate AVP •Pancreas Asthma •Subdural release/action •SAH •SSRIs GU Cystic Fibrosis •Antipsychotics •Bladder CVA •Anti-epileptics •Prostate PPV •NSAIDs •Endometrium Head trauma •MDMA Thymoma MS, GBS Leukaemia Lymphoma Shy-Drager Sarcoma
  • 6. Clinical Features <120 mmol/l <110 mmol/l – Dysgeusia • Drowsiness – Lethargy • Confusion – Anorexia • Depressed reflexes – Nausea, vomiting • Extensor plantar responses – Irritability • Seizures – Headache • Coma – Cramps • Death – Muscle weakness
  • 7. Criteria for SIADH • Bartter and Schwartz (1967) – Hyponatraemia – Clinically euvolaemic – No diuretic use – Serum osmolality <275mOsm/kg – Urine osmolality >100 mOsm/kg – Urine sodium >40mmol/L – Normal thyroid, adrenal and renal function
  • 8. Management - acute • Benzodiapines • Aim for 1-2mmol/L/hr initially – Resolution of neurology – Slow replacement (10 mmol/L/day) • Frusemide (free water excretion) • Find and treat cause
  • 9. TBW = weight * 0.5 (girls) = weight * 0.6 (guys) Na+ to replace = desired change in Na+ * TBW Rate of Na+ replacement = rate of desired change * TBW Rate infusion = Rate of Na+ replacement / (conc of infusate)
  • 10. As a rough guide • To increase Na+ by 1mmol/L/hr – 1 ml/kg/hr of 3% saline – 1.7 ml/kg/hr of 1.8% saline • Max. rate = 70 mmol of Na+/hr • Monitor U&E 2 – 3 hourly
  • 11. Management - Chronic • Risk of osmotic demyelination if change is >12mmol/L/day • Symptomatic – Aim for lower rate of correction (0.5mmol/L/hr) • Asymptomatic – Fluid restrict – Demeclocycline – Oral urea
  • 12. Fluid restriction (Urinary Na + Urinary K) / Plasma Na • >1 – <500ml/day • 1 – 500-700ml/day • <1 – <1L/day
  • 13. Vasopressin Receptor Antagonists • RCTs showed sustained increase in plasma Na compared to placebo • Risk of hypotension with non-selective antagonists • V2 selective antagonists in trials • No reports of osmotic demyelination
  • 14. Osmotic Demyelination Syndrome • Central pontine + extrapontine • Over-enthusiastic correction of Na+ • In chronic hyponatraemia – Brain tissue losses inorganic and organic solutes – Takes few days • Predisposing factors – Alcoholism – Malnourishment
  • 15. Osmotic Demyelination Syndrome • Demyelination • Pontine symptoms – Dysarthria, dysphagia, pseudobulbar palsy – Flaccid quaraparesis • Extra-pontine – Tremor, ataxia, mutism – Parkinsonism, dystonia • Reversible ? – 5% dextrose and desmopressin
  • 17. References 1. “The syndrome of inappropriate antidiuresis”, Ellison et al, NEJM, 2007;356(20):2064-72 2. “Hyponatraemia”, Adrogue & Madias, NEJM, 2000;342(21):1581-89