Common Electrolyte Abnormalities in Hospitalized Children Back...

Common Electrolyte Abnormalities in

Hospitalized Children

Back to Basics

March 8, 2019

Chryso Pefkaros Katsoufis, MD

Assistant Professor of Clinical Pediatrics

Objectives

• Recognize the burden and etiology of dysnatremia developing during the hospitalization of a child

• Describe the changes in clinical practice to address iatrogenic hyponatremia

• Differentiate the potential risks of isotonic fluid administration: Hyperchloremia-Metabolic acidosis-Acute kidney injury-Mortality

SECTION 1

Iatrogenic Dysnatremia

IATROGENIC DYSNATREMIA

Hyponatremia

• Scope of the problem?

– Depends on the defining threshold

• pNa ≤ 115 mmol/L: 41 of 120,000 pediatric admissions to a tertiary referral center– 21 deemed ‘true’

» 12 iatrogenic

» 16 pre-existing medical illness

» 11 symptomatic – cerebral irritability

Dunn K, Butt W. J Paediatr Child Health. 1997


Hyponatremia

• Scope of the problem?

– Depends on the defining threshold

Moritz M, Ayus JC. Pediatr Nephrol. 2010


Clinical Impact of Asymptomatic Hyponatremia

• Adults

– Attention/gait abnormalities

– Falls/fractures

– Increased mortality in pneumonia, heart failure, liver disease

• Preterm neonates

– Poor growth/development

– Sensorineural hearing loss

– Programmed salt hunger in adolescence



Hyponatremic Encephalopathy

• Neuronal adaptation to hyponatremia

– Shift of excitatory osmolytes to the extracellular space

• Glutamate/Aspartate can promote seizure ± cerebral edema



Hyponatremic Encephalopathy

• Risk Factors:

– Age < 16 years

• Relatively larger brain to intracranial volume ratio compared with adults

• Adult-size brain at 6 years vs. adult-size skull at 16 years

– Hypoxemia

– CNS Disease

• 61% of cases = iatrogenic

– Spain; 2000-2010

– 88% of which were receiving intravenous hypotonic fluidsSgouros S, et al. J Neurosurg. 1999

Rodriguez MJ, et al. Acta Paediatrica. 2014


Non-Osmotic Stimuli of Antidiuretic Hormone

• 20% Decrease in BP

– ADH increase by 10-100 pg/mL

• Nausea

– ADH increase by 200 pg/mL

• Percutaneous renal biopsy

– Hyponatremia (<137 mEq/L) developed after 5 hrs, when children received hypotonic IV fluids + elevated ADH levels

Oh GJ, Sutherland SM. Pediatr Nephrol. 2016

Rowe JW, et al. Kidney Int. 1979

Kanda K, et al. Pediatr Nephrol. 2011


Critically Ill & Post-operative Examples

• Post-hoc subgroup analysis:

– Limiting “hypotonic” fluids to a minimum of half-normal saline

– Similar results: Relative Risk 2.42

(95% CI, 1.32-4.45)

Foster BA, Tom D, Hill V. J Pediatr. 2014


Critically Ill & Post-operative Examples

• How much sodium is being administered?

– Infants: 6 mmol/kg (IQR, 3.9-8.1)

– Children: 3.5 (IQR, 3.1-7.8)

– More than 75% of cohort received

more than 3 mmol/kg Na

Bihari S, et al. Crit Care Resusc. 2014


General Ward & Hospital-Wide Examples

110 General Unit, 3ry Care; RCT

• D5% NS vs. D5% ½ NS

1048 Hospitalized Children; Retrospective

• 34.7% Developed Na <135 mEq/L

• Unadjusted OR 1.63; P<0.001– If you received hypotonic saline

• Low Na developed earlier– If you received hypotonic saline

Friedman JN, et al. JAMA Pediatr. 2015

Carandang F, et al. J Pediatr. 2013


Review & Analysis

• JAMA Clinical Evidence Synopsis

– Limitations: “…heterogeneity between the isotonic fluids in included studies. Some studies used 0.9% sodium chloride and others used a balanced fluid containing less chloride.”

McNab S. JAMA. 2015


Yang G, et al. Pediatr Emer Care. 2015


Review & Analysis

• Secondary outcomes of interest

– Hypernatremia

– Hypertension

– Fluid overload

• Up to 2015, the development of hyperchloremic metabolic acidosis is not reported in the randomized controlled trials reviewed and analyzed in at least 10 publications.


Pediatrics. December 2018

NNT with isotonic fluids

to prevent Na <135

mEq/L: 7.5

NNT with isotonic fluids

to prevent Na <130

mEq/L: 27.8


Use of Hypotonic/Restricted IVF

• Restricted volume

– Edema-forming or oliguric states

– 400-600 mL/m2/day

Moritz ML, Ayus JC. Curr Opin Pediatr. 2011


Hypernatremia

• Scope of the problem

– More common in an era when ‘drying out’ the brain was a protective effort to decrease cerebral edema

• pNa ≥ 165 mmol/L: 29 of 120,000 pediatric admissions to a tertiary referral center– 15 iatrogenic

– 15 pre-existing medical condition

– 19 symptomatic – cerebral irritability

Dunn K, Butt W. J Paediatr Child Health. 1997

SECTION 2

Iatrogenic Hyperchloremia, Acidosis

IATROGENIC HYPERCHLOREMIA, ACIDOSIS

What’s Normal?• Compared to serum:

– “Normal” saline = 10% ↑ [Na+], 50% ↑ [Cl-]

• Aqueous phase of plasma water ≈ 150 mEq/L [Na+]

• Tonicity is determined by [Na + K] ≈ 154 mEq/L


Li H, et al. J Zhejiang Univ Sci B. 2016


Strong Ion Difference & pH

• SID = Difference of all fully dissociated cations and anions

– Approximately 40 mmol/L in serum = [Na+] + [K+] – [Cl-]

– ZERO in “normal” saline



Can It Cause Acute Kidney Injury?

• Hyperchloremia was associated with renovascular constriction and reduction in GFR

– Correlated with change in fractional reabsorption of Cl-

• Dog model

Wilcox, CS. J Clin Invest. 1983




• Comparison of 0.9% saline and Plasma-Lyte 148 effects on renal blood flow velocity and perfusion, in 12 healthy adult males, using MRI:

Chowdhury, AH, et al. Ann Surg. 2012



Chowdhury AH, et al. Ann Surg. 2012


AKI (Adult)• Pragmatic, crossover trials:

– 0.9% saline vs. Lactated Ringer’s/Plasma-Lyte

– Outcome MAKE30 = composite of death, dialysis or persistent twofold increase in baseline sCr

1. SMART (Isotonic Solutions and Major Adverse Renal Events Trial – critically ill patients) Marginal OR 0.91, 95% CI 0.84-0.99; P=0.04

2. SALT-ED (Saline against Lactated Ringer’s or Plasma-Lyte in the Emergency Department – non-critically ill) Adjusted OR 0.82, CI 0.70-0.95; P=0.01

1% absolute risk reduction ≈ reduction in MAKE30 by 2 million worldwide

Semler MW, et al. N Engl J Med. 2018

Self WH, et al. N Engl J Med. 2018

Kellum JA. Nat Rev Nephrol. 2018


AKI (Adult)1. SMART (Isotonic Solutions and Major Adverse Renal Events Trial – critically ill

patients) Effect greatest on patients with sepsis, receiving the largest volumes

NNT 20 in sepsis vs. 333 without

2. SALT-ED (Saline against Lactated Ringer’s or Plasma-Lyte in the Emergency Department – non-critically ill) Effect limited to patients who presented with an elevated creatinine

“In the majority of patients who have normal kidney function, are not hyperchloremic, do not have sepsis, and require only modest volume of intravenous

fluids, the use of isotonic saline remains reasonable.”

Kellum JA. Nat Rev Nephrol. 2018

Palevsky PM. Clin J Am Soc Nephrol. 2018


AKI (Pediatric)• Retrospective analyses:

1. 29 PICU’s; 890 children ≤10 years

– Outcome 28-day mortality or persistence of ≥2 organ failures at day 7

Stetson EK, et al. Pediatr Crit Care Med. 2018


AKI (Pediatric)• But is AKI associated with hyperchloremia?

2. 29 PICU’s; 619 Children; 2002-2015

– Outcome day 3 AKI, defined as KDIGO stage 2 or 3

Stetson EK, et al. Intensive Care Med. 2018


AKI (Pediatric)

3. Congenital heart disease, Post-cardiopulmonary bypass– Single-center; 521 patients <72 months

– 88.9% Hyperchloremia within 48 hrs

– Higher Avg & Max [Cl-] associated with AKI in univariate analysis (P<0.005)

– Hyperchloremia not an independent risk factor once adjusted for predictors of AKI in multivariate analysis

Kimura S, et al. J Cardiothorac Vasc Anesth. 2018


Mortality (Adult)

• Retrospective analysis of all hospital admissions to Mayo Clinic Rochester

– 2011-2013: 76,719 unique admissions ≥ 18 years old

– Post-admission sCl increase, due to Cl-rich infusion, independently predicted hospital mortality.

Thongprayoon C, et al. PLoS One. 2017


Mortality (Pediatric)

• Single-center, retrospective cohort; 66 patients; 2008-2016

– Critically-ill; Eventual CRRT requirement

Barhight MF, et al. Pediatr Nephrol. 2018

Management Considerations• Replace volume deficits

– Using isotonic fluids

– Before initiation of maintenance fluids

• On-going losses

– Replace with fluid of commensurate composition and volume

• Monitor

– Daily weights, blood pressure & fluid balance frequently

– Consider daily electrolyte measurements when administering IV fluids

– Consider serum + urine osmolality & urine sodium if HypoNa develops


Management Considerations

• Maintain a high index of suspicion for the potential risks of intravenous fluid therapy

Thank you for your time and attention!

Common Electrolyte Abnormalities in Hospitalized Children Back...

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