HYPERNATREMIA – CASE DISCUSSION

Dr Sasidaran Kandasamy MD DM IDPCCM FPN

Lead Consultant Pediatric Intensivist & Head PICU

Advanced Pediatric Critical Care Center

Dr Mehta Multispecialty Hospitals – CHENNAI - INDIA

20/11/2020 NEPHKIDS 2020 ISN 1

Overview

• Basic Concepts [ Help to solve the Dysnatremia – clinical puzzle !!]

• Case Scenarios on Hypernatremia

Iso to Hypervolemic Hypernatremia [ To understand beyond Fluid prescription!!]

20/11/2020 NEPHKIDS 2020 ISN 2

Understand ‘Link between Na and Water’

• Baseline Na 140 mmol/L [ L – Water is the denominator !!]

• 10% decrease in plasma water – Increases Na to 154 mmol/L [+14]

• 10% Increase in plasma water – Decreases Na to 126 mmol/L [-14]

• Volume Preservation is the primary target in Water Homeostasis

• Maintaining Na 135 -145 mmol/L [Osmolality] is the secondary target

• When there are conflicting signals, Volume Preservation is the priority

20/11/2020 NEPHKIDS 2020 ISN 3

Understand ‘Lab indices useful in Dysnatremia’

1. Urine Osmolality

• Random urine osmolality 300-900 mOsm/Kg

• In dehydration, Urine Osmolality increases > 600

2. Serum Osmolality

• Normal Serum Osmolality 275-295 mOsm/Kg

• Calculated Osmolality:

2 x Na + 2 x K + Glucose /18 + BUN/2.8

3. FENa

• Better compared to spot Urine Na

• [U Na/P Na] x [P Cr/U Cr] x 100

• P Na and U Na in mmol/L

• P Cr and U Cr in µmol/L OR mg/dl

• Lower the FENa Better the TUBULAR REABSORPTION

20/11/2020 NEPHKIDS 2020 ISN 4

Understand ‘Differences in Dysnatremia – hypo Vs hyper’

Timeline Hyponatremia Correction Target Hypernatremia Correction Target

Minutes to hours Excessive correction may NOT be harmful Excessive correction may NOT be harmful

1 -2 days [< 48 hours] Avoid increasing Plasma Na >10mmol / L / day Excessive correction may NOT be harmful[2 mmol/L/hour till S.Na reaches 145mmol/L]

Unknown OR > 48 hours Avoid increasing Plasma Na >8 mmol /L / day Avoid decreasing Plasma Na > 0.5mmol/L/hour

20/11/2020 NEPHKIDS 2020 ISN 5

Iso to Hypervolemic Hypernatremia Algorithm1. Stabilization of ABC and Seizure control.

2. Estimate the VOLUME status: HYPERVOLEMIC - No fluid loss, weight gain, voiding urine

normally, edema, pulmonary edema and respiratory distress. Check ORS/formula

preparation for errors. Confirm by lab: Urine Na > 20 OR FENa > 2 + RFT to calculate eCrCl

3. IV Frusemide as infusion (0.1 - 0.2 mg/kg/hour) to reduce fluid overload. Meticulously

measure UO. Replace UO with Isolyte P or ¼ GNS.

4. Stop 3% Saline or NaHCO3

5. Consider KRT/RRT, if UO low OR Creatinine high (eCrCL < 20ml/min/m2) OR very high

serum Na > 180 OR multiple electrolyte disturbances

20/11/2020 NEPHKIDS 2020 ISN 6

Clinical Case Scenarios

20/11/2020 NEPHKIDS 2020 ISN 7

CASE A

0 D1 D2 D3 D4 D5 D6 D7 D8

• IV Ceftriaxone & Azithro

• IV Acyclovir, Artesunate

D1 - Intubated - P-SIMV+PSAnti-raised ICP measures

A – 5 years Male Child

Fever & Cough 2 days

Altered sensorium – 1 day

Investigation Reports

CSF: 4 cells All Lymphocytes

CSF: Protein & Sugar Normal

CSF: HSV PCR Negative

H1N1 – Positive - Added Oseltamivir

MP Smear – Negative – Artesunate Stopped

•MRI brain with contrast – Normal

•Autoimmune encephalitis considered: IVIG (2g/kg over 48 hours)Child status @ Admn:

• GCS 13/15 – Reducing GCS

• Stridulous breathing +

• Neck Stiffness +

• Positive Kernig’s sign

Febrile EncephalopathyH1N1 Meningoencephalitis

20/11/2020 NEPHKIDS 2020 ISN 8

Sodium trends in CASE A

144

152

159161

152

146

135

140

145

150

155

160

165

Day 1 Day 2 Day 3 Day 4 Day 5 Day 6

Sodium

• 0.9% Saline Maintenance[CHLORIDE Loading]

+ Other Nephrotoxic Medications

20/11/2020 NEPHKIDS 2020 ISN 9

• 3% Saline• Mannitol• IVIG

10 ml/Kg NS x 2

Consequences of Hypernatremia in critically ill

20/11/2020 NEPHKIDS 2020 ISN 10

Creatinine trends in CASE A

0.8

1.9

1.6

1.2

0.7

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

Day 1 Day 3 Day 4 Day 5 Day 6

Creatinine

• Day 3: Creatinine Max 1.9

• eCrCL: 13ml/min/1.73m2 [<20 ml/min/1.73m2 ]

• USG: Mild Hepatomegaly &Renomegaly

• Hypertensive for 72 hours from D3

• D3 Cumulative FO% 3.5% / UO on D3 0.5 ml/kg/hr.

0.9% Saline Bolus 10 ml/Kg x 2

• 3% Saline• Mannitol• Acyclovir• IVIG

• MRI Contrast• Oseltamivir

20/11/2020 NEPHKIDS 2020 ISN 11

Basic principles to prevent NTMx – AKI [In LMIC !!]

1. Check on Circulatory Volume – Keep Euvolemic

2. Always Check Drug-Drug Interaction/ Additive Side Effects when prescribe Polypharmacy

3. Endorse the role of Clinical Pharmacist atleast in Speciality / Super-speciality / ICU units

4. Simple NTMx Checklist may be of use

5. Avoid Aminoglycosides – If no drug level monitoring available

6. Avoid Vancomycin – If no drug level monitoring available

20/11/2020 NEPHKIDS 2020 ISN 12

Common Nephrotoxic Drugs & Mechanism• NSAIDs

• ACEI

• ARB

• Calcineurin Inhibitors

• Drug Combinations [Clarithro + Amlodepine]

• Aminoglycosides

• Amphotericin B

• Chemotherapy Drugs

• ART

• Radio-contrast

• Beta Lactam Antibiotics

• PP Inhibitors, Diuretics

• Phenytoin, Valproate

• Acyclovir

• Ganciclovir

• Foscarnet

• ART

• Mannitol, IVIG, HES

Hemodynamic Changes

ATI

AIN

Intra-tubular Precipitation

Osmotic Nephrosis20/11/2020 NEPHKIDS 2020 ISN 13

CAUTION: Intravenous

Fluid – A Drug !

20/11/2020NEPHKIDS 2020 ISN 14

Management of Index Child

1. IV Frusemide as infusion (0.1 - 0.2 mg/kg/hour) to reduce fluid overload.

2. 4 hourly UO to decide next 4 hours IVF.

3. UO Replacement with ½ DNS.

4. Stopped 3% Saline, Mannitol & Other NTMx medications [Acyclovir]

5. Tolerated Na levels upto 155 mmol/L in view of primary CNS disease in index child

6. Frusemide responsiveness + Favorable Trajectory of Na & Cr

[Trend of decline in Cr & Na] – > Avoided KRT/RRT

20/11/2020 NEPHKIDS 2020 ISN 15

CASE B

0 4 Days. 2hr. 4hr. 8hr.

E – 5 years Male Child

Fever 4 days

Cough & Cold 4 days

Lethargy & depressed sensorium 24 hours

Reduced UO for 24 hours

<----Fever – More than 101 F -->

SEPTIC SHOCK

Fluid Bolus + Epi 0.1 mcg/kg/min

Antibiotics – Vanco + Piptaz

Catecholamine Resistant Shock

Epi 0.3 mcg + NE 0.2 mcg

Hydrocortisone – Shock dose

Ascorbic Acid + Thiamine IV

Ulinastatin started

Admission in PICU

IntubationMechanical VentilationCVL & Art LineLactate 6 EF 45%

20/11/2020NEPHKIDS 2020 ISN 16

Further Course in CASE B….

7 hours In PICU

• Persistent Cold & dusky Peripheries & SpO2 – 70-86 % in ear probe

• Poor PP, Central Pulse + (Poor); IA-BP – SBP 76-82 mmHg

• Adr 0.3 mcg/kg/min + NE 0.2 mcg/kg/min

• Ill sustained Response to Fluid bolus

• Increasing RR (50/min); HR 180-200/min

• ABG: 7.17/94/28/11. Lactate 6

• UO – 0.8 ml/kg/hour since admission

D1

Serum Na 176

Urea 78

Cr 1.1

SGOT 690

SGPT 296

CPK 48,000

Platelet 66,000

PT/APTT 35/55

INR 3.6

Lactate 6

20/11/2020 NEPHKIDS 2020 ISN 17

RRT Options in Critically ill Children

Intermittent Haemodialysis - IHD

Prolonged Intermittent Renal Replacement Therapy – PIRRT Or SLEDD

Continuous Renal Replacement Therapy - CRRT

Acute Peritoneal Dialysis - PD

20/11/2020 NEPHKIDS 2020 ISN 18

Acute PD - Prescription

Components Prescription Guidelines

Catheter Selection • Tenchoff Catheter/ Cook MPD catheter (Optimum Care)• Stiff Stylet Catheter (Minimum Standard)

Exchange volume • Initial Fill volume 10-20 ml/Kg• Maximum Fill volume 30 ml/Kg• Maximum 800 ml/m2 if less than 2years age• Maximum 1100ml/m2 if more than 2 years age• Higher fill volume give greater UF and Clearance

Dialysatecomposition

• Bicarbonate Dialysate [Shock, LF, Newborn] (Optimum Care)• Standard Dialysate• 1.5% Dx to start with – 2.5% to increase UFR

Exchange time • Initial Exchange time 1 hour: 10 min Inflow & 20 min Outflow• Standard Dwell time 30 min• Shorter dwell – Rapid Fluid, Urea, K removal• Hypernatremia – Longer dwell & Reduce Dx%

Additives • Heparin 250 IU/L• K 4meq/L

20/11/2020 NEPHKIDS 2020 ISN

19

Modifications warranted in HypernatremiaComponents Prescription GuidelinesCatheter Selection • Tenchoff Catheter/ Cook MPD catheter (Optimum Care)

• Stiff Stylet Catheter (Minimum Standard)

Exchange volume • Initial Fill volume 10-20 ml/Kg• Maximum Fill volume 30 ml/Kg• Maximum 800 ml/m2 if less than 2years age• Maximum 1100ml/m2 if more than 2 years age

Dialysate composition • Bicarbonate Dialysate [Shock, LF, Newborn] (Optimum Care)• Standard Dialysate [Lactate/ Acetate based]

PD 1.7 [1000 ml Bottle] Dianeal ® Baxter

Na 130 mmol/L Na 132 mmol/L

Cl 100 mmol/L Cl 95

Dx 1.7% 1.5/2.5/4.25 %

Acetate based Solution Lactate based solution

In Hypernatremia – Na >150 mmol/L

Add 3% Saline of calculated volume to keep

∆ Na [ Patient Na- Dialysate Na] = 15 mmol/L

4 hourly Na monitoring is needed to titrate further

20/11/2020 NEPHKIDS 2020 ISN 20

Sodium trends in CASE B

176 180172 166 165

155 152144

0

20

40

60

80

100

120

140

160

180

200

0 hr 8 hr 12 hr 16 hr 24 hr 48 hr 72 hr 96 hr

Sodium

Weight 16Kg; Duration – 5 days

CVVHDF through Rt IJV Line

Filter – M60 Prismaflex cassette. [2 in 5 days]

QB – 50 increased to 90 ml/min

QD – 200 ml/hour; QR – 500 ml/hour [300 pre+ 200 post]

Effluent dose – 44 ml/Kg/hour

CVVHDF

MRSA SepsisMODS

Rate of Na Fall in 16 hours – 1mmol/L/hour

20/11/2020 NEPHKIDS 2020 ISN 21

Creatinine trends in CASE B

1.2

1.4 1.4

1.1

0.7

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

Day 1 Day 3 Day 4 Day 5 Day 6

Creatinine

CVVHDF

Weight 16Kg; Duration – 5 days

CVVHDF through Rt IJV Line

Effluent dose – 44 ml/Kg/hour

PLEX

Filter – TPE 2000 cassette

1.5 times Plasma volume exchange x 2

CRRT StoppedNo further PLEXMinimal Ventilation SupportNo bleeds

20/11/2020 NEPHKIDS 2020 ISN 22

CVVHDF Prescription

Components Prescription Guidelines

Access Selection • IJV/ Femoral Vein• 7F/ 8F/ 10F/ 11.5F Dialysis Catheter• Check Good Forward & Return Flow

Blood Flow RateQB

• 4-5 ml/kg/min• Start at lesser flow and reach 50 – 100 ml/min

Dialyzer/ Filter • HF20 / M60 /M100• HF 20 – Only if weight < 10 Kg

Dialysate Rate QD

Replacement Rate QR

• QD + QF = 2 – 3L/ 1.73m2/ hour• Effluent dose = [QD + QF] – Patient Removal per hour• Target Effluent Dose = 35 ml/Kg/ hour• QD: QF = 1: 1 proportion• QF = 70 % Pre-filter & 30% Post Filter

Anticoagulation • Heparin 20 U/Kg loading followed by 5 - 10U/Kg/hour• NS Flush 50 – 70 ml once in 2 hours [If No Heparin]• APTT Target 50 - 90• ACT Target – 180 - 220

20/11/2020 NEPHKIDS 2020 ISN23

CVVHDF - Modifications in Hypernatremia

20/11/2020 NEPHKIDS 2020 ISN 24

1. Add 3% Saline of pre-calculated volume to make REPLACEMENT Fluid Na = 150-155 meq/L

2. 3% NaCl Volume = [(Target Na – 140)/ (513 – 140)] x Replacement Fluid Rate [ml/hour]

In Index child – QR 500ml/hour

= [(150-140) / (373)] x 500 = 13.5 ml to 500 ml =135 ml to 5L bag

This may be Empirical Best possible Starting point

3. Any rapid fall more than anticipated Na Gradient may mandate Peripheral IV 3% Saline Infusion

4. If Acute Hypernatremia

Na Fall 1-2 mmol/hour is acceptable [ Faster than this…. only in SALT poisoning]

Summary Points

1. Hypernatremia is due to – ‘SALT Gain Vs Excess Electrolyte Free Water Loss’

2. Critically ill children with Hypernatremia – Cause Multifactorial & Effect Multisystemic !!

3. Fluid Therapy Vs KRT in treating Hypernatremia is based on ‘Response Trajectory & AKI Severity’

4. Most of KRT Modifications in Hypernatremia are only ‘Best Empirical Start Point’

5. Monitoring S.Na / S.Cl / Cr / Venous pH may help in ‘Safe & Staggered Na Reduction’

6. Keep stock of Na containing medications & diluents in view of Na Load in index child

7. Keep your Na Targets Individualistic & Context Specific [ Ex S.Na 150-155 in a child with TBI]

20/11/2020 NEPHKIDS 2020 ISN 25

THANK YOU

Dr Sasidaran Kandasamy MD DM IDPCCM FPN

Email: sasidarpgi@gmail.com

20/11/2020 NEPHKIDS 2020 ISN 26

AKI Stages – KDIGO 2012

Stages Serum Creatinine Urine Output1 1.5 to 1.9 times Baseline Creatinine

OR> 0.3mg/dl Increase

<0.5ml/kg/hour for 6-12 hours

2 2.0 to 2.9 times Baseline Creatinine <0.5ml/kg/hour for > 12 hours

3 ≥ 3 times Baseline Creatinine ORCreatinine Increased to > 4.0 mg/dl ORInitiation of Renal Replacement Therapy ORIn patients < 18 years – Decrease in eGFR to < 35 ml/min/1.73m2

< 0.3ml/Kg/ hour for > 24 hoursORAnuria for > 12 hours

20/11/2020 NEPHKIDS 2020 ISN 27