pediatrics grand rounds university of texas health … retractions and is requiring face mask o2....

Pediatrics Grand Rounds 3 May 2013

University of Texas Health Science Center at San Antonio, Texas

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B. AL EX FOST ER, MD, MPH

DIVISION OF INPAT IENT PEDIAT RICS

DEPART MENT OF PEDIAT RICS

Pediatric Grand Rounds: IV Fluid Therapy in Pediatrics

Disclosure:

I have no relationships with commercial companies to disclose

Objectives:

At the end of this presentation the participant will be able to:

1. Describe the historical basis for prescription of IV fluids

2. Understand the pathophysiology of hyponatremia in the hospitalized child

3. Prescribe appropriate IV fluids to a hospitalized child

Outline:

Explore current IV fluid prescribing practice

Review the historical basis for current practice

Outline our current understanding of physiology

Evaluation of the clinical evidence

Synthesis of the clinical evidence

Reconcile history, physiology and clinical evidence for practice

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Case #1:

A patient is admitted to your service due to pneumonia. The patient is tachypneic, has significant retractions and is requiring face mask O2. Therefore, the decision is made to make the child NPO. Which maintenance fluid would you normally choose if the patient is a: 13 y/o girl

6 m/o boy

A. 0.2%NaCl B. 0.45%NaCl C. 0.9%NaCl D. LR

Fluid prescribing: Per the textbook (Nelson’s)

Water requirements: 100mL/kg for first 10kg

50mL/kg for 11-20kg

20mL/kg for every kg above 20 until 2400mL maximum total daily requirement

Translates via dividing by 24hrs into 4-2-1 rule for hourly prescription of water needs

Electrolyte requirements Per the textbook:

Na: 2-4mEq/100kcal/day

K: 1-3mEq/100kcal/day

Using Holliday-Segar: Na: 2-4mEq/100mL water/day

K: 1-3mEq/100mL water/day

Example of H-S in action:

12kg child: Water needs: 100mL/kg*10kg + 50mL/kg*2kg = 1100mL

Na needs (2-4mEq): 1100mL *3mEq/100mL = 33mEq

K needs (1-3mEq): 1100mL* 2mEq/100mL = 22mEq

Water per hour:

1100/24 =45mL/hr (44mL/hr by 4-2-1 rule)

Na: 0.45%NaCl = 77mEq/L *1.1L = 84.7mEq/day

K: 20mEq/L *1.1L =22mEq/day

Therefore, child should receive D5 ½ NS with 20mEq KCl (or even D5 ¼ NS)



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How did we get here

A series of experiments by pioneers in pediatric clinical research

Clinical experience and knowledge emphasized

Tradition has carried us forward

How did we get here… James Gamble, M.D.

Gamble, J. L. et al J Biol Chem 1923.

Daniel Darrow, M.D.

Developed regimen for rehydration 20mL/kg isotonic saline IV

Deficit therapy plus maintenance delivered via hypodermoclysis, oral and IV combined

1st day: hypodermoclysis

2nd day: with D5 and orally

“When one of the students asked what was the treatment for scarlet fever, the doctor replied: "The treatment of scarlet fever depends on what is the matter with the patient.”

Darrow D C. Bull NY Acad Med 1948.

Dr. Darrow’s Work

Maintenance derived from estimates of urinary and insensible losses

Insensible loss scaled to metabolic rate (100-150mL/100kcal/day)

Allan M. Butler, M.D. & Nathan Talbot, M.D.

Provided a basic step towards standardization by defining safe upper and lower limits for water and electrolyte intake

Scaled to surface area instead of metabolic rate

Encouraged use of fluids with both intracellular and extracellular replacement

Talbot N B, Crawford J D, Butler A M. N Engl J Med 1953.

Malcolm Holliday & William Segar

Water needs:

Insensible loss + urinary loss

Correlated energy expenditure to weight using prior data

Since water needs are function of energy expenditure, linked weight and water needs

Holliday M A, Segar W E. Pediatrics. 1957.



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Proof of error at the time

Random urine osmolarity calculated from patients receiving IV fluids for at least 12 hrs


Water & Energy Relationship

Loss of water is a function of energy expenditure

For estimate of insensible losses, used average from all ages of 50mL/100kcal


Urinary losses

Two infants switched from cow’s milk to glucose and water for 5-10 days

Measured their solute excretion

Minimum solute load of 10mOsm in two-fold dilution from blood (150mOsm/L) *1000mL=67mL of urine required

Maximum solute load of 40mOsm in two-fold concentration from blood (600mOsm/L) *1000mL = 67mL of urine required

Total water needs:

50mL from insensible + 66.7mL from urine = 116.7mL water needs/100kcal/day

Assume water of oxidation provides 16.7mL

116.7-16.7 = 100mL/100kcal/day


Electrolyte needs

Again, relating kcal to weight

For Na (3mEq/100kcal/day): 12kg child = 1100kcal/day

1100kcal/day *3mEq/100kcal = 33mEq/day

Recommendation of 0.225%NaCl gives 38.5*1.1 = 42mEq/day


Caveats of Holliday & Segar

“In presenting a simple and arbitrary scheme for computing calories from weight, it is recognized that significant deviations from this relation exist”

“An understanding of the limitations of and exceptions to the system are required… even more essential is the clinical judgment to modify the system as circumstances dictate” - 1957

Maintenance needs only

Still primary method in use today…



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ADH – marriage trouble?

Walum H, et al. Proc. Natl. Acad. Sci. U.S.A. 105 (37): 14153–6. 2008.

Since H & S 1957

Decreased awareness of IV fluid therapy due to sharp decline in severe dehydration and advent of oral rehydration

Arieff et al 1992:

Retrospective review of 16 cases of otherwise healthy children who died or suffered severe neurologic damage from hyponatremia

Retrospective cohort showed incidence of 0.34% of severe (<128mmoL/L) hyponatremia and 8.4% mortality in those affected

Hypotonic fluids identified as potential cause

Flurry of studies and warnings:

Systematic review by Choong et al 2006: Physiology of water regulation

Tonicity is primarily a water regulation driven process

Volume is primarily a sodium regulation issue

Vasopressin (ADH) is primary modulator of water regulation



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Vasopressin (ADH)

Synthesized in paraventricular and supraoptic nuclei of hypothalamus

Transported to posterior pituitary and stored

Classic stimuli for release are osmotic and volume/pressure (at least 8% volume loss)

Plasma osmolality maintained at a tight 285-295mOsm/kg

1% change in osmolality ADH release

Vasopressin action on kidney

Sources: Bichet D, Advances in Chronic Kidney Disease, 2006. Knepper MA. Am J Physiol Cell Physiol. 2012

Hyponatremia:

Need two things: Source of free water

Stimulus for holding onto that water (ADH)

Hypertonic urinary losses (rare)

Source of free water? commonly used IV fluids:

Intravenous Fluid Sodium mEq/L

Osmolality mOsm/kg/H2O

% Electrolyte-Free Water

D5 in Water 0 252 100

D5 with 0.2% NaCl in water

34 321 78


77 406 50

Lactated Ringer’s 130 273 16

5% Dextrose Lactated Ringer’s

130 525 16


154 560 0

Non-osmotic ADH release

Hypovolemia/hypotension

Non-hemodynamic: Pulmonary: asthma, pneumonia, COPD, acute respiratory

failure

Cancer

Nausea, pain, emesis, stress

Post-operative state

Cortisol deficiency

Marathon runners?

Mechanism for non-osmotic release

Increase in vasopressin after IL-6 injection (human & rat) or LPS challenge

Children with diagnosed SIADH after neurotrauma showed high correlation of ADH and IL-6 (r=0.96)

Gionis D et al. J Pediatr Endocrinol Metab. 2003 . Swart RM, Hoorn EJ, Betjes MG, Zietse R. Nephron Physiol. 2011.



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Palin K et al. Am J Physiol Endocrinol Metab 2009.


What we know:

ADH is primary mechanism of water regulation

Putative mechanism for non-osmotic stimulus of ADH in hospitalized patients

Hospitalized patients have: Multiple stimuli for non-osmotic ADH secretion

Potential source of free water in IV fluids

Hypotonic fluids associated with hyponatremia related neurologic injury and death

So what are we doing?

Current Practice:

Survey of pediatric residents in 2009

Freeman MA, Ayus JC, Moritz ML. Acta Paediatr. 2012.

How to address the question of which IV fluids are safe in hospitalized children? Systematic review question:

In hospitalized children age 1 month-18 years assessed to be euvolemic, does hypotonic saline vs. isotonic saline at maintenance rates confer an increased risk of developing hyponatremia defined as a serum sodium<135mmol/L?



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Systematic Review Protocol: Systematic Review Protocol:

Study ID: Subject

characteristics

Inclusion criteria

and setting

Interventions

compared (all

with D unless

noted)

Outcome data

(Na<135mmol/L)

Hypernatremia

(Na>145mmol/L)

Coulthard 2012 n=79, 4-14 years PICU, surgical

(spinal or

craniotomy)

Hartmann’s vs.

0.45% saline

0/39 (0%) in

isotonic; 7/40

(18%) in

hypotonic

None

Rey 2011 n=84, 2-10 years PICU, mixed

surgical (45%)

and medical

156mmoL/L

tonicity vs 50-

70mmoL/L

8/45 (17.8%) in

isotonic; 19/39

(48.7%) in

hypotonic

1/45 (2.2%) in

isotonic; 0/39

(0%) in hypotonic

Yung 2009 n=61, 30 days-18

years

PICU, mixed

surgical and

medical

(undefined)

0.9% saline vs.

0.18% saline

3/29 (10.3%) in

isotonic; 7/32

(21.9%) in

hypotonic

None

Montanana 2008 n=122, 29 days-

18 years

PICU, surgical

(thoracic, cardiac,

abdominal, CNS)

Na140mEq/L,

K15mEq/L

tonicity vs. 20-

100meq/L

3/59 (5.1%) in

isotonic; 13/63

(20.6%) in

hypotonic

1/59 (1.7%) in

isotonic; 1/63

(1.6%) in

hypotonic

Saba 2011 n=37, 3 months-

18 years

Floor, mixed

surgical (67%)

and medical

0.9%saline vs.

0.45%saline

1/16 (6%) in

isotonic; 1/21

(5%) in hypotonic

1/16 (6%) in

isotonic; 0/21

(0%) in hypotonic

Included Studies Study ID: Subject

characteristics

Inclusion criteria

and setting

Interventions

compared (all

with D unless

noted)

Outcome data

(Na<135mmol/L)

Hypernatremia

(Na>145mmol/L)

Choong 2011 n=218, 6 months-

16 years

Mixed floor and

PICU, surgical

0.9% saline vs.

0.45% saline; +/-

KCl

26/106 (24.5%) in

isotonic;

47/112 (42%) in

hypotonic

3/106 (2.8%) in

isotonic; 4/112

(3.3%) in

hypotonic

Neville 2006 n=42, 6 months-

14 years

Floor,

gastroenteritis

0.9% saline vs.

0.45% saline

0/20 (0%) in

isotonic; 5/22

(22.7%)in

hypotonic

None

Brazel 1996 n=12, 12-18 years PICU, surgical Hartmann’s vs.

0.3% saline or

0.18% saline

1/5 (20%) in

isotonic; 7/7

(100%) in

hypotonic

Not reported

Neville 2010 n=124, 6 months-

15 years

Floor, surgical 0.9% saline vs.

0.45% saline

1/31 (3%) in

isotonic; 9/31

(29%) in

hypotonic

None in

maintenance

groups

Kannan 2010 n=114, 3 months-

12 years

Floor, medical 0.9% saline vs.

0.18% saline

5/58 (8.6%) in

isotonic; 13/56

(23%) in

hypotonic

2/58 (3.4%) in

isotonic; 2/56

(3.6%) in

hypotonic

Included Studies cont.

Quick Primer on Meta-analysis

Pools risk estimates from across studies to generate overall estimate of risk

Like a sharp knife

Caveats Cannot improve quality of individual studies and must

therefore assess and include with care

Must assess for heterogeneity of results (I2 from 0-100%)

Assessment of quality of studies:

Study ID: Random

sequence

generation

Allocation

concealment

Blinding of

participants

Blinding of

outcome

Incomplete

outcome data

Selective

reporting

Coulthard

2012

Low Low Low Low Low Low

Rey 2011 Low Unclear Unclear Low High Low

Yung 2009 Low Low Low Low Low Low

Montanana

2008

Low Low Unclear Low Low Low

Saba 2011 Low Low Low Low High Low

Choong 2011 Low Low Low Low Low Low

Neville 2006 Unclear Low High Low High Low

Brazel 1996 Unclear Unclear Unclear Low Low Low

Neville 2010 Unclear Low High Low High Low

Kannan 2010 Low Low High Low Low Low



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Results: Comparison of at least ½ NS with isotonic fluids:

Conclusion:

Translating into number needed to treat (harm): 5.26 (95% CI: 3.85-9.09)

If you treat 5 patients with hypotonic fluids, 1 will develop a serum Na<135.

Unable to assess risk for significant hyponatremia (Na<125)

Hypotonic fluids including 1/2NS carry risk of harm used at maintenance rates in euvolemic patients

Alternate hypotheses:

Holliday 2007: recognized need for less water but argued that isotonic fluids

not the answer

need to be better clinicians and assess volume status better

Counter:

Neville 2010: subjects receiving hypotonic fluids at ½ maintenance had similar risk of hyponatremia as those receiving at maintenance

Yung 2009: fluid type but not rate (2/3 maintenance) was predictor of hyponatremia

Potential dangers of isotonic fluids

Fluid overload: Heart failure, liver failure, renal failure

Hypernatremia:

Especially in diabetes insipidus

Increased risk not seen in published data on general population

Hyperchloremic metabolic acidosis: Concern primarily with 0.9%NaCl; documented case series;

seen primarily with resuscitation-level volumes, not maintenance

Case #2:

A patient is admitted to your service due to a clinical presentation and initial LP findings concerning for meningitis. The patient is irritable and mildly somnolent, and has been unable to take PO. Which maintenance fluid would you normally choose if the patient is a: 6 m/o M

13 y/o F

A. 0.2%NaCl B. 0.45%NaCl C. 0.9%NaCl D. LR



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Where from here?

Recommendation of AAP statement on IV fluids in pediatrics to raise awareness of problem and forge potential consensus

Recommendation of not using any IV fluids routinely and definitely not ½ NS as routine maintenance

Further questions include: Why aren’t hypotonic oral rehydration fluids problematic?

Possible non-ADH induced anti-diuresis as possible pathway

Better defining best treatment of SIAD/SIADH

Thanks:

Vanessa Hill & Dina Tom - collaborators

Michelle Arandes – letting me muck around

Holliday, Segar and all the old dudes – their invaluable contributions and observations

Erin & Atticus Foster – support and humor

Questions?

Treatment of hyponatremia:

Based on neurologic symptoms, not a pure numbers game

If clinically stable, fluid restriction before hypertonic saline if Na>120

If symptomatic (altered, seizures) 3% saline to correct quickly 2-4mmol/L and until symptomatic improvement

Total correction of deficit should be done over 48hrs Total body water (TBW) x (desired SNa – actual SNa)

0.6*20kg x (140-125) = 180 mEq

pediatrics grand rounds university of texas health … retractions and is requiring face mask o2....

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