Hyponatremia and hypernatremia

1. Presented by: Dr Vineet Chowdhary Moderator: Dr Chandrashekar Chatterji Hyponatremia And Hypernatremia & its Anaesthetic Implications

2. Sodium is the most prevalent cation in the extracellular fluid (ECF), with a normal level of around 135- 145mmol/L & intracellular concentration of around 10mmol/L Total body Sodium is about 5000 mEq in a normal adult person Responsible for 90% of total osmolality of ECF Daily requirement of sodium is about 100 mEq or 6gm Major function of sodium is to maintain ECF volume and therefore blood pressure In normal individuals, the kidney strives to achieve Na +  balance – that is, to have Na +  excretion equal to Na +  ingestion. The long-term control of blood pressure is achieved by the excretion or retention of Na +  (and hence plasma volume) in the kidney SODIUM REGULATION:PHYSIOLOGICAL BASIS

3. Hormones increasing sodium reabsorption:   Renin : - Released from the juxtaglomerular apparatus of the kidney - Release is stimulated by: raised sympathetic tone, falling plasma volume, and certain prostaglandins, such as PGE 2 - No direct effects promoting Na +  retention, it controls the renin-angiotensin-aldosterone axis   Angiotensin II : - Levels rise as result of renin release - In turn, it stimulates the release of aldosterone - Also increases tone in the efferent glomerular arteriole. The net effect is to enhance Na +  reabsorption from the proximal tubule.   Aldosterone : - Steroid hormone released from the adrenal cortex - End product of the renin-angiotensin-aldosterone system - Acts on the distal tubule and collecting duct to increase Na +  and water reabsorption (proportionately more Na +  than water) Hormonal Regulation of Sodium

4.   Arginine vasopressin (AVP) , AKA   anti-diuretic hormone (ADH ): -ADH is produced in neuron cell bodies in supraoptic and p araventricular nuclei of the Hypothalamus , and s tore d in posterior pituitary. - passive absorption of water from the collecting ducts, concentrating the urine - Causes a small degree of Na +  reabsorption, but the retention of water is proportionately much greater · 

5. Hormones increasing sodium excretion :   Atrial Natriuretic Peptide (ANP): - A small peptide produced from the atrial wall as a result of atrial stretching due to hypervolaemia - Acts to increase Na (and hence water) excretion by increasing GFR and blocking Na reabsorption in the proximal collecting duct Other factors secreted by the hypothalamus, termed brain natriuretic peptides (BNP) , may have similar roles.

6. Types and distribution Include guanylin , uroguanylin , lymphoguanylin and exogenous peptide toxin produced by enteric bacteria Function In gastrointestinal tract, stimulate epithelial secretion of Cl - and HCO - , causing enhanced secretion of fluid and electrolyte into the intestinal lumen. in kidney , increase excretion of Na + , Cl - , K + and water The Guanylin family

7. Serum sodium concentration regulation Stimulation of thirst Secretion of ADH Feedback mechanism of Renin- Angiotensin -Aldosterone Renal handling of filtered sodium Stimulation of thirst :(a) Increase in osmolality is the main driving force which is sufficient if it increases by 2-3 %. (b) A decrease in blood pressure or volume by 10-15 % Thirst centre is located in the anterolateral centre of the Hypothalamus Secretion of ADH is triggered by increase in osmolality by approx 1% or the vol. or pressure of the vascular sytem . This increases the passive absorption of water and urea concentrating the urine. Renin- Angoitensin - Aldosterone axis acts to cause retention of sodium in the event of decreased osmolarity Physiology

8. Definition: Hyponatremia is defined as a plasma Na + concentration <135 m Eq /L It is due to a relative excess of water in relation to sodium. It can result from excessive loss of sodium from excessive sweating, vomiting, diarrhoea, burns, and diuretics . It is a very common disorder, occurring in up to 22% of hospitalized patients. Result of an increase in circulating AVP and/or increased renal sensitivity to AVP, combined with any intake of free water; a notable exception is hyponatremia due to low solute intake. HYPONATREMIA

9. Patients’ intravascular volume status must be evaluated to understand further the underlying problem leading to abnormalities in sodium physiology. Hyponatremia thus is subdivided diagnostically into three groups, depending on clinical history and volume status : hypovolemic, euvolemic , and hypervolemic

10. I- Hypo- osmolar hyponatremia (true hyponatremia ) Hypovolemic Hyponatremia Euvolemic Hyponatremia Hypervolemic Hyponatremia II- Pseudo hyponatremia Normal Osmolality High Osmolality TYPES:

11. Patient dehydrated; reduction in total body sodium exceeds reduction in total body water NON RENAL LOSSES ( Urinary Sodium excretion < 20 mEq /L)- Vomiting, Diarrhea, Third space losses, Pancreatitis, Burns RENAL LOSSES (Urinary Sodium excretion > 20 mEq /L)- The renal causes of hypovolemic hyponatremia share an inappropriate loss of Na + - Cl – in the urine, leading to volume depletion and an increase in circulating AVP . Causes include reflux nephropathy recovery phase of acute tubular necrosis, diuretics ,mineralocorticoid deficiency, osmotic diuresis, ketonuria Hypovolemic Hyponatremia

12. “Cerebral salt wasting" : rare cause of hypovolemic hyponatremia , and inappropriate natriuresis in association with intracranial disease Associated disorders include subarachnoid hemorrhage , traumatic brain injury, craniotomy, encephalitis, and meningitis . Cerebral salt wasting typically responds to aggressive Na + - Cl – repletion.

13. Patient has a normal store of sodium but an excess of total body water The most common form seen in hospitalized patients.  The most common cause is the inappropriate administration of hypotonic fluid The syndrome of inappropriate antidiuresis is the most common cause of euvolemic hyponatremia Other causes include glucocorticoid therapy, stress, drugs , hypothyroidism. Euvolemic Hyponatremia

14. Most common cause of euvolemic hyponatremia The osmotic threshold and osmotic response curves for sensation of thirst are shifted downward High levels of ADH are secreted intermittently at an abnormally low threshold or continuously despite low osmolality. The presence of hyponatremia plus a urine osmolality higher than maximal dilution confirms the diagnosis. Urinary sodium concentration usually exceeds 30 mEq /L The fractional excretion of sodium is greater than 1%. Patients with SIADH exhibit a characteristic response to water restriction; a 2- to 3-kg weight loss is accompanied by correction of hyponatremia and cessation of salt wasting over 2 to 3 days SIADH

15. Increase in total body water exceeds increase in total body sodium. Patients are edematous. RENAL CAUSES(urinary sodium > 20mEq/L): Acute or Chronic renal failure NON RENAL CAUSES : CHF, Cirrhosis, nephrotic syndrome Hypervolemic Hyponatremia

16.   Normal Osmolarity - Due to a measurement error which can result when the solid phase of plasma (that due to lipid and protein) is increased - Typically caused by hypertriglyceridaemia or paraproteinaemia .  High Osmolarity : Translocational hyponatraemia - Occurs when an osmotically active solute that cannot cross the cell membrane is present in the plasma. -In the case of the insulinopaenic diabetic patient, glucose cannot enter cells and hence water is displaced across the cell membrane, dehydrating the cells and “diluting” the sodium in the serum. - This is also the cause of hyponatraemia seen in the TURP syndrome, in which glycine is inadvertently infused to the same effect. Psuedo hyponatremia

17. Severity of symptoms depends upon the severity of hyponatremia and the rate at which the sodium concentration is lowered. Acute – develops in 48 hours or less. Subjected to more severe degrees of cerebral edema Chronic- develops over 48 hours and brain edema is less and is well tolerated. The signs and symptoms are due to increase in volume of ICF and increase in volume of brain cells rather than decrease in serum sodium. CLINICAL FEATURES

18. SIGNS AND SYMPTOMS OF HYPONATREMIA Central Nervous System Mild – Apathy ,Headache, Lethargy Moderate- Disorientation, Psychosis, Agitation, Ataxia Confusion Severe-Stupor, Coma, Pseudobulbar palsy Tentorial   herniation , Cheyne -Stokes respiration, Death Gastrointestinal System Anorexia, Nausea ,Vomiting Musculoskeletal System Cramps Diminished deep tendon reflexes

19. History and physical examination- to identify hypovolemic hyponatremia ( diarrhoea , vomitting , burns) Radiologic imaging - to assess whether patients have a pulmonary or CNS cause for hyponatremia . CT scanning of the thorax should be considered in patients at high risk small cell carcinoma Laboratory tests - Provide important initial clue in the differential diagnosis Plasma Osmolality Urine Osmolality Urine Sodium concentration Uric acid level Serum potassium Serum glucose DIAGNOSIS

20. Plasma Osmolality- Normal plasma osmolality is 275-290 mEq /l . >290 mEq /L- hyperglycemia or administration of mannitol 275-290 mEq /L- Hyperlipidemia or hyperproteinemia <275 mEq /L- Evaluate volume status 1. Increased Volume- CHF, Cirrhosis, Nephrotic syndrome 2. Euvolemic - SIADH, Hypothyroidism, psychogenic polydipsia 3. Decreased Volume- GI and 3 rd space loss, renal losses Urine Osmolality- Normal value is > 100 mosmol /kg Normal to high : Hyperlipidemia, hyperproteinemia , hyperglycemia, SIADH < 100 mosmol /kg Hypo- osmolar hyponatremia - Excessive sweating, Burns,Vomiting , Diarrhea , Urinary loss

21. Urine Sodium >20 mEq /L SIADH, diuretics <20 mEq /L cirrhosis, nephrosis , congestive heart failure, GI loss, skin, 3 rd spacing, psychogenic polydipsia Uric Acid Level < 4 mg/dl consider SIADH FeNa (Fractional Excretion of Sodium) Help to determine pre-renal from renal causes Serum glucose - also should be measured; plasma Na + concentration falls by 1.6 to 2.4 m M for every 100-mg/ dL increase in glucose due to glucose-induced water efflux from cells; this "true" hyponatremia resolves after correction of hyperglycemia Serum Potassium : Hyperkalemia - Renal insufficiency or Adrenal insufficiency with hypoaldosteronism Hypokalemia - with metabolic acidosis suggests vomiting or diuretic therapy

22. Treatment needs to be individualized considering etiology, rate of development, severity and clinical signs and symptoms Hyponatremia which developed quickly needs to be treated fast whereas slow developing hyponatremia should be corrected slowly GOALS of THERAPY: 1. To raise the plasma sodium concentration at a slow rate 2. To replace sodium or potassium deficit or both 3. To correct underlying etiology BASIC PRINCIPLES OF CORRECTION: Rapid correction is indicated in acute (<48hours) symptomatic or severe hyponatremia .(serum Na <120 mEq /L) In chronic cases patients are at little risk, however rapid correction can lead to demylination . Use slower acting therapies like water restriction TREATMENT

23. Treatment of acute symptomatic hyponatremia Hypertonic 3% saline (513 m M ) to acutely increase plasma Na + concentration by 1–2 m M /h to a total of 4–6 m M ; alleviate severe acute symptoms, after which corrective guidelines for "chronic" hyponatremia are appropriate The increase in plasma Na + concentration can be highly unpredictable during treatment , plasma Na + concentration should be monitored every 2–4 h during treatment Vasopressin antagonists do not have an approved role in the management of acute hyponatremia . Treatment of chronic hyponatremia Rate of correction should be comparatively slow < 8–10 m M in the first 24 h and <18 m M in the first 48 h to avoid ODS

24. Hypovolemic hyponatremia will respond to intravenous hydration with isotonic normal saline, with a rapid reduction in circulating AVP and a brisk water diuresis. Diuretics induced hyponatremia is treated with saline and potassium supplementation Hypervolemic hyponatremia responds to no salt, water restriction(intake< urine output), and loop diuretics Euvolemic hyponatremia will respond to successful treatment of the underlying cause, with an increase in plasma Na + concentration Regardless of the initial rate of correction, chosen acute treatment is stopped once 1. patient’s symptoms are abolished 2. A safe plasma sodium (120-125 mEq /L) is achieved

25. SPECIFIC THERAPY: 1. Removal of responsible drugs- diuretics, chlorproamide etc 2. Management of physical stress or post operative pain 3. Specific treatment of underlying cause 4. Vasopressin antagonists ( vaptans ) are highly effective in treating SIAD and hypervolemic hyponatremia , reliably increasing plasma Na + concentration as a result of their aquaretic effects (augmentation of free-water clearance). Most of these agents specifically antagonize theV 2 vasopressin receptor TO CALCULATE NEED OF REPLACEMENT SODIUM CONTAINING FLUID: 0.9% saline (154mEq/L) and 3% NaCl - hypertonic saline (513 mEq /L) are the only two routinely used I.V. fluids . However 0.9% NS is not used to correct hyponatremia in SIADH

26. estimate SNa change on the basis of the amount of Na in the infusate ΔSNa = {[Na + K] inf − SNa } ÷ (TBW + 1) ΔSNa is a change in SNa [Na + K] inf is infusate Na and K concentration in 1 liter of solution Total Body Water= 0.6* B.W(kg) in children and nonelderly man =0.5*B.W.(kg) in nonelderly woman and elderly man =0.45*B.W.(kg) in elderly women

27. Asymptomatic or Chronic SIADH response to isotonic saline is different in the SIADH In hypovolemia both the sodium and water are retained Sodium handling is intact in SIADH A dministered sodium will be excreted in the urine, while some of the water may be retained possibly worsening the hyponatremia Water restriction 0.5-1 liter/day Salt tablets Demeclocycline Inhibits the effects of ADH Onset of action may require up to one week

28. Hypernatremia is defined as an increase in the plasma Na + concentration to >145 m M . Considerably less common than hyponatremia , hypernatremia nonetheless is associated with mortality rates as high as 40–60 %. Hypernatremia is caused by a relative deficit of water in relation to sodium which can result from Net water loss: accounts for majority of cases pure water loss hypotonic fluid loss Hypertonic gain results from iatrogenic sodium loading HYPERNATREMIA

29. Net water loss Pure water loss Unreplaced insensible losses (dermal and respiratory) Hypodipsia Neurogenic diabetes insipidus Post-traumatic tumors, cysts, histiocytosis , tuberculosis, sarcoidosis Idiopathic aneurysms, meningitis, encephalitis, Guillain-Barre ´ syndrome Congenital nephrogenic diabetes insipidus Acquired nephrogenic diabetes insipidus Renal disease (e.g. medullary cystic disease) Hypercalcemia or hypokalemia Drugs ( lithium, methoxyflurane , amphotericin B, vasopressin V 2 -receptor antagonists) Causes of Hypernatremia

30. Hypotonic fluid loss Renal causes Loop diuretics Osmotic diuresis (glucose, urea, mannitol ) Post obstructive diuresis Polyuric phase of acute tubular necrosis Gastrointestinal causes Vomiting Nasogastric drainage Entero cutaneous fistula Diarrhea Use of osmotic cathartic agents (e.g., lactulose) Cutaneous causes Burns Excessive sweating

31. Hypertonic sodium gain Hypertonic sodium bicarbonate infusion Ingestion of sodium chloride Ingestion of sea water Hypertonic sodium chloride infusion Primary hyper- aldosteronism Cushing’s syndrome

32. The symptoms of hypernatremia are predominantly neurologic . Altered mental status is the most common manifestation, ranging from mild confusion and lethargy to deep coma . The sudden shrinkage of brain cells in acute hypernatremia may lead to parenchymal or subarachnoid haemorrhages and/or subdural hematomas; however, these vascular complications are encountered primarily in paediatric and neonatal patients Osmotic damage to muscle membranes also can lead to hypernatremic rhabdomyolysis Clinical Features

33. HISTORY AND PHYSICAL EXAMINATION: The history should focus on the presence or absence of thirst, polyuria, and/or an extrarenal source for water loss, such as diarrhoea The physical examination should include a detailed neurologic exam and an assessment of the ECFV; patients may be hypovolemic, with reduced JVP and orthostasis Accurate documentation of daily fluid intake and daily urine output LAB INVESTIGATIONS: Measurement of serum and urine osmolality in addition to urine electrolytes - The appropriate response to hypernatremia and a serum osmolality >295 mosmol /kg is an increase in circulating AVP and the excretion of low volumes (<500 mL/d) of maximally concentrated urine, i.e., urine with osmolality >800 mosmol /kg DIAGNOSIS

34. Diabetes insipidus may result from a deficiency of ADH (vasopressin) or inability of the kidney to produce a hypertonic medullary interstitium Diabetes insipidus is characterized by production of a large volume of dilute urine. Deficiency of vasopressin is known as central diabetes insipidus .Vasopressin deficiency is seen after pituitary surgery, basal skull fracture, and severe head injury. Nephrogenic diabetes insipidus is defined as renal tubule cell insensitivity to the effects of vasopressin. In patients with DI a significant amount of body water is lost in a short period, which can cause profound hypovolemia Diabetes Insipidus

35. Patients with continued urine output of more than 100 mL/ hr who develop hypernatremia should be evaluated for diabetes insipidus by determining the osmolalities of urine and serum . If the urine osmolality is less than 300 mOsm /L, and serum sodium exceeds 150 mEq /L, the diagnosis of diabetes insipidus is likely. Patients with central DI should respond to the administration of intravenous, intranasal, or oral Desmopressin . Patients with NDI due to lithium may reduce their polyuria with amiloride (2.5–10 mg/d ) Thiazides may reduce polyuria due to NDI Occasionally ( NSAIDs) have been used to treat polyuria associated with NDI

36. A two-pronged approach: Addressing the underlying cause Correcting the prevailing hypertonicity RATE OF CORRECTION: Hypernatremia that developed over a period of hours (accidental loading) Rapid correction improves prognosis without cerebral edema Reducing Na + by 1 mmol /L/ hr appropriate Hypernatremia of prolonged or unknown duration a slow pace of correction prudent maximum rate 0.5 mmol /L/ hr to prevent cerebral edema A targeted fall in Na + of 10 mmol /L/24 hr Management

37. Reduce serum sodium concentration to 145 mmol /L Make allowance for ongoing obligatory or incidental losses of hypotonic fluids that will aggravate the hypernatremia In patients with seizures prompt anticonvulsant therapy and adequate ventilation Administration of Fluids Water ideally should be administered by mouth or by nasogastric tube as the most direct way to provide free water, i.e., water without electrolytes . Alternatively, patients can receive free water in dextrose-containing IV solutions such as 5% dextrose Goal of Treatment

38. Hypernatremia with ECF vol contraction- Isotonic saline is given initially till ECF vol is restored. Subsequently water deficit can be replaced with water by mouth or I.V. 5% dextrose or 0.45% NaCl Hypernatremia with increased ECF volume : since hypernatremia is secondary to solute administration it can be rapidly corrected . Patients are volume overloaded- loop diuretic is given along with water to remove sodium excess

39. If at all possible, hyponatremia , especially if symptomatic, should be corrected prior to surgery . Level above 130mEq/L is considered safe If lower than 130 mEq /L it can be the cause of :- 1. Cerebral edema 2. Decreased MAC 3. Post op agitation and confusion 4. Problems of hypervolemia If the surgery is urgent, then appropriate corrective treatment should continue throughout the surgery and into the postoperative period . ANAESTHETIC IMPLICATIONS OF HYPONATREMIA

40. Frequent measurement of serum sodium is necessary to avoid overly rapid correction of hyponatremia with resultant osmotic demyelination or overcorrection resulting in hypernatremia. Treatment of the underlying cause of the hyponatremia should also continue throughout the perioperative period . Induction and maintenance of anesthesia in patients with hypovolemic hyponatremia are fraught with the risk of hypotension. In addition to fluid therapy, vasopressors and/or inotropes may be required to treat the hypotension Hypovolemic patients are sensitive to the vasodilating and negative inotropic effects of the volatile anesthetics , barbiturates, and agents associated with histamine release (morphine, meperidine , curare, atracurium ).

41. Dosage requirements for other drugs must also be reduced to compensate for decreases in their volume of distribution. Hypovolemic patients are particularly sensitive to sympathetic blockade from spinal or epidural anesthesia. If an anesthetic must be administered prior to complete correction of the hypovolemia , ketamine may be the induction agent of choice for general anesthesia; etomidate may be a suitable alternative.

42. It involves the resection of the prostate via a cystoscope with continuous irrigation of the bladder. The irrigating fluid is a nonelectrolyte fluid containing glycine, sorbitol, or mannitol , and this fluid may be absorbed rapidly causing volume overload, hyponatremia , and hypo-osmolality . An awake patient permits detection of the signs of hyponatremia , including nausea, vomiting, visual disturbances, depressed level of consciousness, agitation, confusion, coma, seizures, muscle cramps, and death. In TURP syndrome-

43. Cerebral edema occurs at or below a serum level of 123 mEq /L, and cardiac symptoms occur at 100 mEq /L. It can result in pulmonary edema , hypertension, and heart failure. [19] Monitoring - direct neurologic assessment in the patient under regional anesthesia - M easurement of serum sodium concentration and osmolality in the patient under general anesthesia. Treatment -Terminating the surgical procedure - D iuretics if needed for relief of cardiovascular symptoms - H ypertonic saline administration if severe neurologic symptoms are present or the serum sodium concentration is less than 120 mEq /L.

44. Overly rapid correction of hyponatremia (>8–10 m M in 24 h or 18 m M in 48 h) also is associated with a disruption in integrity of the blood-brain barrier. The lesions of ODS classically affect the pons Clinically , patients with central pontine myelinolysis can present one or more days after overcorrection of hyponatremia with para - or quadraparesis , dysphagia, dysarthria, diplopia, a "locked-in syndrome," and/or loss of consciousness . Other regions of the brain also can be involved in ODS. In order of frequency, the lesions of extrapontine myelinolysis can occur in the cerebellum, lateral geniculate body, thalamus, putamen, and cerebral cortex or subcortex . OSMOTIC DEMYLINATION SYNDROME

45. Development of ataxia, mutism , parkinsonism, dystonia, and catatonia is seen in these Relowering of plasma Na + concentration after overly rapid correction can prevent or attenuate ODS However, even appropriately slow correction can be associated with ODS, particularly in patients with additional risk factors; these factors include alcoholism, malnutrition, hypokalemia , and liver transplantation.

46.   ( a ) Normal MRI scan taken five months before the episode of severe hyponatremia, when serum sodium was 140 mmol/l. ( b ) Ten days after the episode of severe hyponatremia, MRI scan showed bilateral high-intensity abnormalities in the lenticular nuclei and in the head of the caudate nucleus (arrows). ( c ) At day 32, the lesions shown in panel b appear more pronounced (arrows). ( d ) At day 32 with fluid-attenuation inversion recovery, high intensity lesions were also observed in the precentral gyrus (arrows) Severe hyponatremia followed by extrapontine myelinolysis

47. Osmolar gap is considered significant when the difference between the measured and calculated osmolarity is > 10 Some critically ill patients have an unexplained osmolar gap which is thought to result from escape of osmotically active intracellular solutes into extracellular fluid I ncreased membrane permeability to Na and decreased active removal of sodium from the cells by energy dependent cation exchange pump leads to redistribution hyponatremia with increased osmolar gap- a concept called sick cell syndrome . This state has been described during a great variety of human diseases such as traumatic shock, diabetic ketoacidosis, lactic acidosis and multiple organ failure  Both the osmolar gap and hyponatremia correct simultaneously in this condition as the primary illness is treated Sick Cell Syndrome

48. If at all possible, surgery should be delayed until the hypernatremia has been corrected or at least until symptoms have abated . Frequent serum sodium measurements will be required perioperatively , and invasive hemodynamic monitoring may be useful . Hypovolemia will be exacerbated by induction and maintenance of anesthesia and prompt correction of hypotension with fluids, vasopressors, and/or inotropes may be required. Increased MAC seen in animal studies ANAESTHETIC IMPLICATION OF HYPERNATREMIA

49. THANK YOU