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Di and siadh
- 1. SIADH AND DI By: DR. MESTET Y. ( Neurosurgery resident)
- 2. Objective • Understand Physiology of ADH in water metabolism • Explain the Pathophysiology of SIADH & DI • Mention causes of SIADH & DI • Be able to diagnose & manage SIADH & DI • Know the natural course of SIADH & DI 6/16/2020 2
- 3. Physiology of ADH release and action 6/16/2020 3
- 5. Regulation of Osmolality Primary regulator of ADH release = Plasma osmolality 6/16/2020 5
- 6. Regulation of Sodium and water excretion Regulated independently: sodium by aldosterone and ANP; and water by ADH. Regulation of urine volume • Normally by ADH in response to changes in water intake. • How about in SIADH? 6/16/2020 6
- 7. SIADH Impaired Water excretion + unsuppressible ADH Pathophysiology: • ADH-induced water retention + Dilutional hyponatremia • Volume expansion induced natriuresis Euvolemic hyponatremia Potassium loss. why? 6/16/2020 7
- 8. Five patterns of ADH release in SIADH Type A: ADH unresponsive to osmotic deviations. Type B (a "reset osmostat“): abnormally low osmotic threshold for ADH release but normal osmoregulation. Type C: ADH is persistently in the physiologic range regardless of plasma osmolality. 6/16/2020 8
- 9. Type D (NEPHROGENIC SIADH) : normal osmoregulation but concentrated urine. Type E: altered baroreceptor mediated release of ADH despite normovolemia. 6/16/2020 9
- 10. SIADH - causes Intracranial – infection, stroke, hemorrhage, tumor, very common in SAH population (69%) Intrathoracic – malignancy, abscess, effusion, PTX, chest wall deformity Drugs – vasopressin, DDAVP, oxytocin, analgesics, antidepressants, amiodarone, antipsychotics, sulfonylureas, carbamazepine, cyclophosphamide Extracranial tumors – small-cell lung CA, pancreatic CA HIV/AIDS Hereditary – “gain-of-function” V2 receptor mutation Major surgery **** Idiopathic 6/16/2020 10
- 11. Presentation Mild or gradual hyponatremia • anorexia, • Nausea, • headache, • difficulty concentrating, • irritability, • dysgeusia and • muscle weakness. Severe hyponatremia or a rapid drop (> 0.5 mEq/hr) • can cause neuromuscular excitability, cerebral edema, muscle twitching and cramps, • vomiting • confusion, • seizures, • Respiratory arrest and • neurologic deficit, • coma or death. 6/16/2020 11
- 12. 6/16/2020 12
- 13. Treatment for SIADH • Rx of hyponatremia depends on : 1. Severity 2. Duration 3. Signs and symptoms 4. Volume status 6/16/2020 13
- 14. Aggressive Rx protocol. 1. severe hyponatremia + either acute /severe symptoms Rx: ICU 3% saline: (how?) and Lasix 20 m g IV q d (how?) goal: raise [Na+] by 1–2 m Eq/L/hr 6/16/2020 14
- 15. Estimated rise in Na+ Fluid restriction recommendation The Furst formula 6/16/2020 15
- 16. II. Intermediate Rx protocol. 1. symptomatic non severe hyponatremia 2. severe chronic hyponatremia plus mild -moderate symptoms Rx: 0.9% NS infusion + Lasix 20 m g IV q d conivaptan for refractory cases goal: raise [Na+] by 0.5– 1m Eq/L/hr. 6/16/2020 16
- 17. III. Routine treatment protocol and maintenance therapy. 1. asymptomatic non severe hyponatremia or 2. asymptomatic chronic severe hyponatremia Rx: a) fluid restriction: dietary salt and protein encouraged. C/I: hyponatremia in SAH 6/16/2020 17
- 18. b) for refractory cases • Demeclocycline & conivaptan • Furosemide 20 mg po bid. • Urea • lithium : not recommended Treat the cause of SIADH Mgt of SIADH in SAH Prognosis of SIADH : most transient 6/16/2020 18
- 19. 6/16/2020 19
- 20. Complication: ODS At 2-6 days of rapid correction. Rare (0.5% of ICU patients). Rapid vs slow adaptation 6/16/2020 20
- 21. Effects of hyponatremia on the brain and adaptive mechanism: The “Osmotic Theory” 6/16/2020 21
- 22. Risk factors for ODS • Serum sodium at presentation • sodium concentrations • severe liver disease • Discontinuation of desmopressin when hypontremia occur. • Overly rapid rate of correction • malnutrition 6/16/2020 22
- 23. Treatment of ODS Proactive/Reactive/Rescue Prevention: for exceeded correction limits Re-lower serum sodium to a 48-hour target value. (why)? monitor serum sodium every 2-3 hrs. MRI to see demyelination. Prognosis: 60% recover completely. 6/16/2020 23
- 24. Cerebral Salt Wasting (csw) • ADH-independent condition xcried by Hyponatremia & hypovolemia. • Primary problem: natriuresis unlike SIADH. • Secondary problem: hypovolemia mediated ADH release • Pathophysiology: 2 theories 1. BNP release by brain (more accepted) 2. Impaired sympathetic neural input Absent potassium wasting.(why?) 6/16/2020 24
- 25. Causes SAH…more common cause (7%) CNS infections Stroke Head injury CNS tumors CNS surgery – usually within the first 10 days 6/16/2020 25
- 26. Diagnosis • Evidence of volume depletion • Increased urine output Laboratory Findings Na < 135 mEq/L Low Posm Uosm > 300 mOsm/kg UNa > 40 mEq/L High BUN Increased Cr Low uric acid Increased albumin 6/16/2020 26
- 27. Rx • Treat with volume repletion – 0.9% NaCl – 3% NaCl – Fludrocortisone – salt tablets • Prognosis: most resolve within 3-4 weeks. 6/16/2020 27
- 28. Diabetes insipidus (DI) • is a disorder of water homeostasis xcrized by: polyuria (>3L or >3ml/kg/hr) & <300mosm/kg of dilute urine and polydipsia due to the deficiency of ADH or resistance to its receptors. 6/16/2020 28
- 29. Epidemiology • DI is the most common (10–30%) complication after pituitary surgery. 6/16/2020 29
- 30. Types of DI • Central DI: most common • Nephrogenic DI • Gestational DI: placental cysteine aminopeptidase • Dipsogenic DI: no effective rx todate. • Adipsic DI: Challenging to manage Dehydration is uncommon in most di except in Adipsic . 6/16/2020 30
- 31. CAUSES OF DI 6/16/2020 31
- 32. Patterns of post op di • Abrupt onset (within 12–24 hr) after surgery. • 3 patterns 1. Transient 2. Permanent: if > 85–90% neurons injured. 3. Triphasic pattern (3%) 6/16/2020 32
- 34. Diagnosis of DI 6/16/2020 34
- 35. Rx of central DI 6/16/2020 35
- 36. An intact thirst mechanism and are able to drink • free water po • DDAVP: for how long? • what if normal serum sodium & iv maintenance fluid therapy needed? • serum sodium at least every 24 h 6/16/2020 36
- 37. Uconsciousness or unable to take po Assess volume status. volume depleted: restore with 0.9% NS Deficit Free hypotonic fluid if euvolemic. Move to oral or NGT water as quickly as is clinically safe. IV or IM 1–2 μg DDAVP Monitor serum Na+ (every 4h;at least every 12 h), K+ & RFT. 6/16/2020 37
- 38. Rx of Nephrogenic DI • Rx underlying pathology • Prostaglandin inhibitors • Thiazide diuretics • drugs that increase ADH release or enhance ADH effect on the kidney such as chlorpropamide, carbamazepine 6/16/2020 38
- 39. 6/16/2020 39
- 40. Natural history of traumatic (surgical) DI Most recover completely (50% of in 1 week and 80% in 3 months). • long term DI only in 2–7% (most subtle but should be recognized and managed). 6/16/2020 40
- 41. References • Greenburg neurosurgical book 8th edition • Fluid, Electrolyte and Acid-Base Disorders 2018 • Medscape 2019 • Up-to-date 2018 • Journal of endocrinology 2018 • Journal of neurology 2018 • Journal of neurosurgery 2018 6/16/2020 41
Editor's Notes
- ADH acting at V1a and V1b receptors primarily cause vasoconstriction and adrenocorticotropic hormone (ACTH) release, respectively.
- Plasma & urine osmolality is inversely related.
- with chronic SIADH, sodium loss is more prominent than water retention [3]. Since potassium is as osmotically active as sodium, the loss of potassium contributes to the reductions in plasma osmolality and sodium concentration. The lost potassium is derived from the cells and probably represents part of the cell's volume regulatory response [3]. Cells that increase in size due to water entry in hyponatremia lose potassium and other solutes in an attempt to restore cell volume.
- If further testing is required, the follow ing are options, but are rarely recomm ended: 1. m easure serum or urinary levels of ADH. Rarely indicated since urine osm olality > 100 m Osm /kg is usually su cient to indicate excessive ADH.1 ADH is norm ally undetectable in etiologies of hyponatrem ia other than SIADH 2. water-load test: considered to be the definitive test.11 The patient is asked to consum e a water load of 20 m l/kg up to 1500 m l. In the absence of adrenal or renal insu ciency, the failure to excrete 65% of the water load in 4 hrs or 80% in 5 hrs indicates SIAD. CONTRAINDICATIONS: this test is dangerous if the starting serum [Na+] is ≤ 124 m Eq/L or if th e patient has sym ptom s of hyponatrem ia
- Increasing solute excretion by giving salt or urea will increase the urine volume and tend to raise the serum sodium. There are three components to the treatment of hyponatremia in SIADH: ●Treatment of the underlying disease, if possible ●Initial therapy to raise the serum sodium ●Prolonged therapy in patients with persistent SIADH If the serum sodium concentration is to be elevated, the electrolyte concentration of the fluid given must exceed the electrolyte concentration of the urine, not simply that of the plasma [5].
- The Adrogué–Madias formula help estimate the expected increase in natremia (mmol/L) (after the administration of 1000mL of infusate)=(Infused sodium [mmol/L]−serum sodium [mmol/L])/Total body water (L)+1. The Furst formula: (Na+u+K+u/Na+p) is helpful for taking decisions in mild to moderate cases because it makes it possible to predict the effectiveness of WR: if the result of the formula is >1, the patient is not excreting free water by the renal route, and is unlikely to improve with WR.35
- Oral salt tablets — The principles described in the above section on intravenous saline also apply to oral salt intake. Suppose the same 60 kg woman with a serum sodium of 120 mEq/L and total body water of approximately 30 L takes in 9 g of salt (154 mEq each of sodium and chloride) in tablet form. All 154 mEq will be excreted since sodium handling is normal, which will increase the urine output by 500 mL if the urine cation concentration (ie, urine [Na] + urine [K]) is 308 mEq/L and by approximately 1000 mL if the urine cation concentration is 154 mEq/L. Maintenance therapy — Unless the SIADH is reversible (eg, postoperative or due to a drug that can be discontinued), effective therapy of symptomatic hyponatremia must be followed by maintenance therapy to prevent a subsequent reduction in serum sodium and possible symptom recurrence. The goal serum sodium is discussed below. (See 'Asymptomatic hyponatremia' below.) One or more of the above therapeutic modalities may be required. The usual sequence of maintenance therapy is as follows: ●Fluid restriction – The suggested goal fluid intake in hyponatremic patients with SIADH is less than 800 mL/day [4]. An important exception is patients with a recent subarachnoid hemorrhage in whom fluid restriction can be deleterious. (See 'Fluid restriction' above and 'Subarachnoid hemorrhage' above.) ●Oral salt – In patients with SIADH, administering oral salt will increase the urine output; the usual initial dose is 3 g or one-half teaspoon three times daily, resulting in a total dose of 9 g per day. Since sodium handling is normal and the urine osmolality is relatively fixed in SIADH, increasing oral salt intake will, in a dose-dependent fashion, increase the urine volume. (See 'Oral salt tablets' above.) ●Oral urea – In patients with SIADH who can tolerate its bitter taste, administering oral urea will increase urine output; the usual dose is 15 to 30 g per day. Increasing oral urea will, in a dose-dependent fashion, increase the urine volume. In the calculations described above, the intake of 15 g of urea would be expected to increase the urine output by approximately 500 mL if the urine osmolality is 500 mosmol/kg and by 1000 mL at a urine osmolality of 250 mosmol/kg. ●Reduce the urine osmolality – In patients with more severe SIADH (urine osmolality more than twice the plasma osmolality), the efficacy of both fluid restriction and increased salt intake will be reduced (see 'Intravenous hypertonic saline' above). If further therapy is necessary, the next step is to increase urinary water excretion by impairing the mechanism of urinary concentration. This can be achieved by loop diuretic therapy (eg, furosemide 20 mg orally twice a day). Loop diuretic therapy can produce hypokalemia and hypovolemia since the diuretic response is higher in patients with SIADH who usually have normal or near-normal renal function and are not sodium avid. (See 'Salt plus a loop diuretic' above.) For the reasons described above, we do not use tolvaptan, demeclocycline, or lithium for maintenance therapy in patients with asymptomatic hyponatremia. (See 'Limitations to use of tolvaptan' above and 'Demeclocycline or lithium' above.)
- Thus, hyponatremic patients with SAH should be treated with hypertonic (3 percent) saline to both preserve cerebral perfusion and prevent complications from hyponatremia-induced brain swelling. One proposed regimen is an initial infusion rate of 20 mL/h with subsequent dosing being dependent upon serial measurements of serum sodium at six-hour intervals [10]. Fluid therapy in normonatremic patients with SAH is discussed elsewhere.
- Csw is a much less common cause of hyponatremia than SIADH.
- Restoration of euvolemia in CSW should remove the stimulus to ADH release, resulting in a dilute urine and correction of the hyponatremia. As mentioned above, this has not been documented in CSW. Lack of urinary dilution does not necessarily preclude CSW since it might be expected that patients with subarachnoid hemorrhage would also have SIADH. For patients with documented CSW, salt tablets can be administered once the patients are able to take oral medications. Administration of a mineralocorticoid, such as fludrocortisone, can also be used [29,37,38]. Long-term therapy of CSW is not necessary since CSW tends to be transient [9]. Resolution usually occurs within three to four weeks.
- The presence of both serum hyperosmolality and hypernatremia is highly suggestive for DI, but these laboratory alterations can be absent if the patient is conscious and has free access to water Polyuria:urinary volume >150 ml/Kg/24 hours at birth, >100-110 ml/Kg/24 hours up to the age of 2 years, and >50 ml/Kg/24 hours in older children and adults (1). a urine output exceeding 3 L/day in adults and 2 L/m2 in children.
- Hypodipsic (Adipsic) Hypernatremia Based on hypertonic saline infusion, four types of osmoreceptor dysfunction (thirst and ADH release) have been described in hypodipsic patients: (1) reset osmostat, (2) decreased osmoreceptor function, (3) complete thirst osmoreceptor dysfunction, and (4) absence of thirst with intact ADH release. Among these four types, only types A and C are common.
- A defect in the thirst mechanism, located in a person's hypothalamus, causes dipsogenic diabetes insipidus. This defect results in an abnormal increase in thirst and liquid intake that suppresses vasopressin secretion and increases urine output. The same events and conditions that damage the hypothalamus or pituitary—surgery, infection, inflammation, a tumor, head injury—can also damage the thirst mechanism. Certain medications or mental health problems may predispose a person to dipsogenic diabetes insipidus. Researchers have not yet found an effective treatment for dipsogenic diabetes insipidus. monitor the patient’s blood sodium levels to prevent hyponatremia, or low sodium levels in the blood. Adipsic DI Attenuated thirst response Challenging to manage Present acutely with signs and symptoms of dehydration. Hypothalamic lesions, craniopharyngioma, CNS trauma, CNS tumors, CNS neurosurgical procedures Most DI do not manifest dehydration. Why?
- Salt-wasting nephropathy: Not usually a cause of polyuria — As a general rule, underlying renal disease can impair sodium conservation in the presence of volume depletion. However, except in rare cases of Bartter syndrome [21], salt-wasting nephropathies do not cause true polyuria. This is in part due to the phenomenon of tubuloglomerular feedback in which increased sodium chloride delivery to the macula densa (due to decreased reabsorption in the more proximal segments) results in afferent arteriolar constriction and a fall in glomerular filtration rate, thereby limiting the degree of sodium chloride loss
- Di with no polyuria Biphasic pattern: first two phases only is more common than the triphasic pattern
- Withholding water (eg, for diagnostic or surgical procedures) in adults with DI can result in severe dehydration. Thus, if oral intake has to be withheld, the patient should be hospitalized and hydrated intravenously and the plasma sodium concentration closely monitored while intake is restricted. The water restriction test for the evaluation of polyuria involves measurement of the urine volume and osmolality every hour and the plasma sodium concentration and osmolality every two hours. We generally recommend that the patient stop drinking two to three hours before coming to the office or clinic; overnight fluid restriction should be avoided since potentially severe volume depletion and hypernatremia can be induced in patients with marked polyuria. The water restriction test in adults is continued until one of the following end points is reached: ●The urine osmolality reaches a clearly normal value (above 600 mosmol/kg), indicating that both ADH release and effect are intact. Patients with partial DI may have a substantial rise in urine osmolality but not to this extent. ●The urine osmolality is stable on two or three successive hourly measurements despite a rising plasma osmolality. ●The plasma osmolality exceeds 295 to 300 mosmol/kg or the plasma sodium is 145 mEq/L or higher.
- CHOICE OF THERAPY — There are three main options for the treatment of polyuria in patients with central DI: ●Desmopressin, which is an ADH analog and is the preferred drug in almost all patients. ●Other drugs, such as chlorpropamide, carbamazepine, thiazide diuretics, and nonsteroidal anti-inflammatory drugs. ●A low-solute (mostly low-sodium, low-protein) diet. The choice of therapy varies with the severity of the polyuria. Patients with partial DI and mild to moderate polyuria and nocturia may be adequately controlled with a low-solute diet (if acceptable to the patient) and, if necessary, a thiazide diuretic. Although these modalities also reduce the urine output in patients with marked polyuria and nocturia, desmopressin therapy is usually required for symptom control. Desmopressin can also be used in patients with less severe DI who do not want to comply with a low-solute diet.
- Desmopressin therapy should be continued for as long as the patient has symptomatic central DI. There are few long-term data on the use of the tablet form of desmopressin. In one study, eight children with central DI were treated and followed for up to 3.5 years [12]. There was no attenuation of the antidiuretic effect, and no side effects or antibody formation were noted. In another report, ten adults had satisfactory maintenance of the antidiuretic effect over one year with doses of 0.3 to 0.6 mg/day given in two to three doses per day; doses larger than 0.2 mg had no greater effect, eg, 0.4 versus 0.2 mg, but probably lasted longer [13]. drugs that increase ADH release or enhance ADH effect on the kidney such as chlorpropamide, carbamazepine, clofibrate, and nonsteroidal anti-inflammatory drugs.