Pediatrics Grand Rounds University of Texas Health … retractions and is requiring face mask O2....
Transcript of 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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Pediatrics Grand Rounds 3 May 2013
University of Texas Health Science Center at San Antonio, Texas
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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)
Pediatrics Grand Rounds 3 May 2013
University of Texas Health Science Center at San Antonio, Texas
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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.
Pediatrics Grand Rounds 3 May 2013
University of Texas Health Science Center at San Antonio, Texas
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Proof of error at the time
Random urine osmolarity calculated from patients receiving IV fluids for at least 12 hrs
Holliday M A, Segar W E. Pediatrics. 1957.
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
Holliday M A, Segar W E. Pediatrics. 1957.
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
Holliday M A, Segar W E. Pediatrics. 1957.
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
Holliday M A, Segar W E. Pediatrics. 1957.
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…
Pediatrics Grand Rounds 3 May 2013
University of Texas Health Science Center at San Antonio, Texas
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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
Pediatrics Grand Rounds 3 May 2013
University of Texas Health Science Center at San Antonio, Texas
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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
D5 with 0.45% NaCl in water
77 406 50
Lactated Ringer’s 130 273 16
5% Dextrose Lactated Ringer’s
130 525 16
D5 with 0.9% NaCl in water
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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University of Texas Health Science Center at San Antonio, Texas
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Mechanism for non-osmotic release
Palin K et al. Am J Physiol Endocrinol Metab 2009.
Mechanism for non-osmotic release
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
Pediatrics Grand Rounds 3 May 2013
University of Texas Health Science Center at San Antonio, Texas
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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
Pediatrics Grand Rounds 3 May 2013
University of Texas Health Science Center at San Antonio, Texas
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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