1. HYPO &HYPERNATREMIA IN ICU
DR.Hardik Patel

2. BASIC PHYSIOLOGY SERUM OSMOLARITY (mM) = 2*Na +BUN/2.8+GLUCOSE/18
SODIUM IS MAJOR ECF CATAION, mEq/L
REGULATION OF OSMOLARITY BY
- COUNTERCURRENT MECHANISMS OF KIDNEY
- HYPOTHALAMUS via ADH,THIRST

3. PHYSIOLOGY SR.OSMOLALITY > 290mOsm/Kg |
THIRST & ADH STIMULATION –RETENTION OF FREE WATER WITH CONCEN.URINE
RESTORATION OF NORMAL SR. OSMOLALITY
THIRST & ADH SUPPRESSTION –EXCRETION OF EXCESS WATER WITH DILUTE URINE
HYPERNATREMIA if unable to retain water
-Absent or Ineffective ADH
- Inadequate water intake
HYPONATREMIA if unable to EXCRETE water
-Nonsuppressed ADH,ECTOPIC SECRETION
-Excessive water intake

4. Hyponatremia Defined as sodium concentration < 135 mEq/L
Generally considered a disorder of water as opposed to disorder of salt.
Incidence is 15-20% in ICU while 4-5% in Outpatients.
Clinical Features : Asymptomatic, nausea, vomiting, lethargy, convulsions, coma, death
Depends upon severity & duration.

5. Psuedohyponatremia
Psuedohyponatremia –Hyperproteinemia,Hyperlipidemia can cause falsely depressed sodium levels
Hyperosmolar Hyponatremia
-Hyperglycemia – Glucose acts as an osmotically active solute ,shifts water from ICF to ECF – dilutional hyponatremia. Plasma Sodium falls by 2.4mEq/L for every 100mg/dL rise in the plasma glucose above normal.
Corrected Na = 0.016(Measured glucose-100)+Measured Na
-Mannitol,Glycine like hypertonic infusions

6. HYPOOSMOLAR HYPONATREMIA
HYPERVOLEMIC
HYPOVOLEMIC
EUVOLEMIC
CHF
EXTRA RENAL LOSSES
SIADH (Uosm > 100mOsm/kg)
NEPHROTIC SYNDROME
URINE Na CONCEN
<15 mEq/L
PSYCHOGENIC POLYDIPSIA
(Uosm < 100mOsm/kg
CIRRHOSIS
RENAL FAILURE
VOMITING,DIARRHEA,PANCREATITIS,BURNS
HYPOTHYROIDISM
CORTISOL DEFICIENCY
RENAL LOSSES
Urine Na >20 mEq/L
BEER POTOMANIA
LIKE RECENT DIURETICS,CEREBRAL SALT WASTING,ADRENAL INSUFFICIENCY
TEA & TOAST DIET

7. Ecstasy use – increased water intake with inappropriate ADH secretion
Surgical – TURP SYNDROME, Hypotonic fluids
NSIAD – Nephrogenic syndrome of inappropriate antidiuresis – Hereditary disorder that presents with low sodium levels in newborn males with undetectable ADH levels
Reset Osmostat – Occurs in elderly and pregnancy where regulated sodium set point is lowered

8. VOLUME STATUS
Hypovolemic – urine output, dry mucous membranes, sunken eyes
Euvolemic – normal appearing
Hypervolemic – Edema, past medical history, Jaundice (cirrhosis), S3 (CHF),Oliuria (CRF)

9. Workup for Hyponatremia
3 mandatory lab tests
Serum Osmolality
Urine Osmolality
Urine Sodium Concentration
Additional labs depending on clinical suspicion
TSH, cortisol (Hypothryoidism or Adrenal insufficiency)

10. Interpretation Serum Osmolality Urine Osmolality
Can differentiate between true hyponatremia, pseudohyponatremia and hyperosmolar hyponatremia
Urine Osmolality
To differentiate between primary polydipsia(ADH suppression, Uosm <100mOsm/kg,Sp.gravity<1.003) and impaired free water excretion like in SIADH( ADH secretion present, Hence High Uosm)
Urine Sodium concentration
Can differentiate between Extra Renal hypovolemia like vomiting,diarrhea,Peritonitis (U Na<20mEq/L) and Renal losses like Recent Diuretics,Adrenal insufficiency,Cerebral salt wasting (UNa >40mEq/L)

11. DATASETS Hyponatremia
With hypokalemia & Met.Alkalosis – Diuretics,vomiting
With hypokalemia & Met. Acidosis –
Diarrhea or laxative abuse
With hyperkalemia & Met. Acidosis –
Adrenal insufficiency

12. Additional Tests TSH – high in hypothyroidism
Cortisol – low in adrenal insufficiency, though may be inappropriately normal in infection/stressful state, therefore should get Cortisol-Stimulation test to confirm
Head CT and Chest Xray – May see evidence of cerebral salt wasting or small cell carcinoma which can both cause hyponatremia

13. SIADH Etiologies
CNS disease – Tumor, infection, SAH, Wernicke’s Encephalopathy ,CVA, Head injury
Pulmonary disease – TB, pneumonia,Atelectasis , empyema, pneumothorax
Cancer – Lung (Oat cell Ca), thymoma , ovarian Ca
Drugs – Cyclophosphamide , Cisplatine , Carbamazepine ,chlorpropamide, NSAIDs, desmopressin ,oxytocin
Surgery – Postoperative (Pain stimulates ADH),Mitral commissurotomy ( acute decrease in LAP)
HIV/AIDS – Pneumonia, Meningitis, Malignancy
Idopathic – most common

14. PATHOPHYSIOLOGY OF SIADH
Inappropriate/Excessive ADH activity | Water retention, Volume Expansion = HypoNa Reduced Renin,Angio II,Aldosterone,Raised ANP Natriuresis, Diuresis = euvolemia

15. Main diagnostic criteria for SIADH
Clinical Euvolemia, absence of hypotension,edema
Hypotonic Hyponatremia
Normal hepatic, renal and cardiac function
Normal thyroid and adrenal function
Urine osmolality greater than 100 mOsm/kg though generally greater than mOsm/kg in setting of low serum osmolality (ADH inappropriate)
Urine sodium level greater than 20 mEq/L
Low serum uric acid & BUN are common findings.

16. Cerebral Salt Wasting Syndrome
Etiology – Neurosurgery, Head trauma especially SAH
Mechanism- Excessive Renal Na Excretion
?BNP &/or loss of renal sympathetic tone
Loss of Na – Volume depletion – release of ADH
However with volume resuscitation hyponatremia doesn’t correct perhaps due to concomitant ADH release from damaged brain
In few cases, Fludrocortisone may help

17. CEREBRAL ADAPTATION
Hypoosmolality – shift of water from ECF to cells, cell swelling, Brain edema
Adaptation- raised interstitial pressure moves fluid to CSF,brain cells loose solutes like K,Na then OSMOLYTES like amino acids,glutamine,taurine & hence water.
Asymptomatic despite Na levels mEq/L in CHF or SIADH
Rapid Decline- Seizures, Coma, brain herniation, sometimes death

18. Treatment Of Hyponatremia
Treatment depends upon symptoms & duration
Hypovolemic Hyponatremia
ABC, Fluid Resucitation with 0.9%N.S.
Oral salt intake
Diuretic Induced – 0.9% NS with K supplementation.
Adrenal insufficiency – Treat the Cause,Hydrocort.
CSW: Volume resucitation, Fludrocortisone.

19. Hyponatremia in edematous states
Diuretics, Fluid Restriction(Intake<Output),
Salt restriction rather than supplementation,
correction of K
Treatment of the underlying Cause
Use of ADH antagonists like tolivaptan in CCF

20. Treatment of Euvolemic Hyponatremia
Fluid restriction is 1 st step in Euvolemic pts.
Treatment of SIADH
Fluid restriction & salt tablets
Demeclocycline – diminishes effect of ADH on receptors. Dose is mg/day.
Nephrotoxic, Photosensitivity
Tolvaptan, Conivaptan
3% NS via Central line.
Polydipsia – Fluid Restriction,Daily monitoring of Weight , Omission of drug causing dry mouth

21. Severe symptoms present
As stated earlier, symptoms dictate treatment
If severe symptoms are present, starting bolus of 100 ml of 3% hypertonic saline which generally raise serum sodium level by 2-3 mEq/L
Goals for correction:
1.5 to 2 mEq/L per hour for first 3-4 hours until symptoms resolve
Increase by no more than mEq/L in first 24 hrs

22. Formulas that may help: How much sodium does the patient need?
Sodium deficit = Total body water x (desired Na – actual Na)
Total body water is estimated as lean body weight x 0.5 for women or 0.6 for men
Adrogue – Madias Equation
Change in Na per liter=
(infusate Na+K – Serum Na) / (TBW in kg +1)

23. How about an example: 70 kg man with sodium level of 110 with coma
To increase Na levels by 4 mEq/L in 2 hrs with 3% Saline, using Adrogue- madias eq^n
Change in Na per liter = /42+1= 9.37mEq/L. Hence Amount of 3% NS required to change by 4 mEq/L= 4/9.37 = 0.4L =400 ml
Rate of Infusion =400ml/2 hr=200ml/hr

24. What if the sodium increases too fast?
The dreaded complication of increasing sodium too fast is Central Pontine Myelinolysis which is a form of osmotic demyelination
Symptoms generally occur 2-6 days after elevation of sodium and usually either irreversible or only partially reversible
Symptoms include: dysarthria, dysphagia, paraparesis, quadriparesis, lethargy, coma or even seizures

25. Risk Factors for demyelination
Rate of correction over 24 hours more important than rate of correction in any one particular hour
More common if sodium increases by more than 20 mEq/L in 24 hours
Very uncommon if sodium increases by 12 mEq/L or less in 24 hours
CT but preferably MRI to diagnose demyelination if suspected, though imaging studies may not be positive for up to 4 weeks after initial correction

26. Treatment Options CPM is associated with poor prognosis
Prevention is key
Small studies have shown that plasmapharesis done immediately after diagnosis may improve clinical outcomes

27. VAPTANS Conivaptan – An antagonist to both the V1 & V2 receptors
For intravenous use only, In hospital use only
Dose : single 20 mg bolus iv over 30 mins
Causes sustained water diuresis, phlebitis, Liver dysfunction
Tolvaptan- Specific V2 receptor antagonist, Dose is 15 mg OD
Given orally, initiated in hospital with sodium monitoring
Satavaptan,Lixivaptan..

28. Summary of Hyponatremia
Hyponatremia has variety of causes
Treatment is based on symptoms
Severe symptoms = Hypertonic Saline
Mild or no symptoms = Fluid restriction
Overcorrection, more than 12 mEq increase in 24 hours must be avoided with monitoring
Serum Osmolality, Urine Osmolality and Urine sodium concentration are initial tests to order

29. Hypernatremia
Produced by either administration of hypertonic fluids or much more frequently, loss of thirst
Because of extremely efficient regulatory mechanisms such as ADH and thirst, hypernatremia generally occurs only in people with prolonged lack of thirst mechanism
Patients with loss of ADH (Diabetes Insipidus) usually can compensate with increased fluid intake

30. Causes of Hypernatremia
Unreplaced water loss
Insensible and sweat losses
GI losses
Diabetes Insipidus (both central and nephrogenic)
Hypothalamic lesions which affect thirst or osmoreceptor function – Primary hypodipsia, essential hypernatremia, Reset osmostat in Mineralocorticoid excess
Water loss into cells like in seizures,severe excercise
Sodium Overload – Infusion of Hypertonic sodium bicarbonate, 3% NS

31. Symptoms of Hypernatremia
Initial symptoms include lethargy, weakness altered mental status,irritability
Polyurea,Thirst,signs of hypovolemia(Hypertonic)
Can progress to twitching, seizures, obtundation or coma
Brain shrinkage can lead to rupture of cerebral veins leading to IC hemorrhage, SAH

32. Diagnosis of Hypernatremia
Same labs as workup for hyponatremia: Serum osmolality, urine osmolality and urine sodium
Urine sodium should be lower than 25 mEq/L if a water and volume loss are in cause. It can be greater than 100 mEq/L when hypertonic solutions are infused or ingested
If urine osmolality is lower than serum osmolality then DI is present
Administration of DDAVP will differentiate
Urine osmolality will increase in central DI, no response in nephrogenic DI

33. WATER DEPRIVATION TEST
PRECONDITION – Pt should stop drinking water 2 -3 hrs prior to beginning of Water restriction.
Measuring Urine volume & osmolality every hr while Plasma Na & Osmolality every 2 hourly
Interpretation

34. Decreased urine output, Uosm > 600 mOsm/Kg|
NO RESPONSE = D.I.
Response to AVP
________________
Decreased urine output, Increased Uosm
NO RESPONSE = D.I. Response to AVP
_____________________
NO RESPONSE TO AVP
Primary Polydipsia
Central D.I.
Nephrogenic D.I

35. Treatment of Hypernatremia
ABC, stop ongoing losses.
Correct Water deficit = TBW x {(plasma Na/desired Na level)-1}
Adrogue Madias Equation
Safe rate of correction is 1 mEq/L / 2 hrs, fast correction leads to cerebral edema.
Sodium free 5% Dextrose, Plain water orally/NGT
70 kg woman with lassitude & Sr Na 160 mEq/L. She is having 1L of urine output & Diarrheal loss of 2 L.Replacement fluid chosen is 5% Dextrose

36. Expected change in Na per lit of 5% Dextrose=
0-160/42+1= mEq/L
Hence to correct Na by 0.5 mEq/L, 1000ml of D5 to be given in (3.72/0.5=7.44), 8hrs.
Hence infusion rate should be 1000/8=125ml/hr.
To account for on going water loss 3000ml per day/24 hrs=125ml/hr.
Total fluid to be given= =250ml/hr

37. Calculation continued
Free Water deficit = TBW*{(SERUM Na/140)-1}
= 42([160/140]-1) = 6L
Overcorrection can lead to cerebral edema which can lead to encephalopathy, seizures or death
The 6 L which will lower the sodium level by 20 should be given over hours, plus ongoing losses 3L/ day, so 6L over 48 hrs, total 6+6 =12 L in 48 hrs. Hence rate of infusion 12000ml/48= 250ml/hr

38. Summary of Hypernatremia
Loss of thirst usually has to occur to produce hypernatremia
Rate of correction same as hyponatremia
D5 water infusion is typically used to lower sodium level
Same diagnostic labs used: Serum osmolality, Urine osmolality and Urine sodium
Beware of overcorrection as cerebral edema may develop

39. SALT Trial And EVEREST Trial , The New England Journal of Medicine, September 2012
- Multicenter, randomised, double blind,placebo controlled trial for efficacy of Tolvaptan in hyper or euvolemic hyponatremia
Conclusion: In pts hospitalised for congestive heart failure,oral Tolvaptanin in addition to diuretics improved many but not all CHF signs & symp oms,without serious ADR.

40. Thank You