acid base, fencl, figge, stewart, anion gap, corrected anion gap, outcomes, mortality, ICU length of stay, education, medical

1. Advanced Acid/Base on the PICU
David Schmidt
SUMMA / Clinician Scientists Training Program

2. Stewart 101

3. Definitions
• Ions, Kations, Anions
• Strong electrolytes and weak electrolytes
• Acid
• pH

4. Governing principles
• Law of Electrical Neutrality
• Law of Mass Conservation
• Law of Mass Action
Acid Base Chemistry
H2O! "# H+
+OH$
Kd =
[H+
][OH$
]
H2O
Kd
=
the
dissocia-on
constant
Dependent
on
temp,
molecular
structure

5. Strong vs weak electrolytes (e.g. acids)
KA =
[H+
][A!
]
[HA]
HA! "# H+
+ A$
HA
=
an
acid
H+
=
a
hydrogen
ion
that
lost
an
electron
A-­‐
=
a
deprotonated
acid
Ka
=
the
dissocia-on
constant
for
the
acid
(a)
NaCl(s) H 2O
! "!! Na+
+Cl#
(aq)
S
=
solid
Aq
=
aqueous

6. Proteins = acids and bases
Alberts,
NCBI
Bookshelf
Albumin
(weak
acid)
IgA
(weak
acid)
IgG
(weak
ka-on)

7. Stewart’s Message:
[H+] and [HCO3
-]
are dependent

8. Strong Ion Difference (SID)
• Completely dissociated ions at body pH
1 organic acids with a pKa <4 (’strong acids’)
2 strong electrolytes
• Q: Law of electrical neutrality?
• Unmeasured anions: e.g. lactate, ketones, SO4
2-
• Unmeasured kations: e.g. lithium, Mg, Ca
pKa
=
acid
dissocia-on
constant
SID =[strongkations]![stronganions]
"[Na+
]+[K+
]![Cl!
]

9. Weak non-volatile acids
HA! "# H+
+ A$
ATOT = HA+ A!

10. Meet the Stewart players
• Strong ion difference
• Non-volatile weak acids
• pCO2
These determine
• H+
• HCO3-
by
• Law of Electrical Neutrality
• Law of Mass Conservation
• Law of Mass Action

11. The formulas that govern acid base status
HA! "# H+
+ A$
SID +[H+
]![HCO3
!
]![CO3
2!
]![A!
]![OH!
]= 0
For
each
acid
(including
water)
CO3
2-­‐
=
carbonate
A-­‐
=
total
anionic
weak
non-­‐vola-le
acids
CO2 + H2O CA
! "# H2CO3 ! "# H+
+ HCO3
$

12. SID & pH
PCO2
is
held
constant
at
40
mm
Hg.
ATOT
20
mEq/L
Morgan
TJ.
Clin
Biochem
Rev.
2009
May
13;30(2):41–54.

13. SID & pH
PCO2
is
held
constant
at
40
mm
Hg.
SID
=
42mEq/L
Morgan
TJ.
Clin
Biochem
Rev.
2009
May
13;30(2):41–54.

14. Summary
• Strong ion difference
• Non-volatile weak acids
• pCO2
These determine
• H+
• HCO3-

15. Stewart Acid Base Physiology

16. Stewart Acid Base Status
www.acidbase.org
Paul
Elbers,
MD
©

17. Stewart Acid Base Status
www.acidbase.org
Paul
Elbers,
MD
©

18. Stewart Acid Base Status
www.acidbase.org
Paul
Elbers,
MD
©

19. Hyperchloremic SID acidosis
• 0.9% saline
• Rapid infusion
– reduces SID (metabolic acidosis)
– reduces ATOT (metabolic alkalosis)
SID change predominates over ATOT
• SID changes may also be induced by low Cl- fluids
– 0.45% saline
– mannitol
– 5% dextrose
Morgan.
Clin
Biochem
Rev
2009

20. Fluids & Stewart Acid Base
• The balanced crystalloid
SID lower than plasma (acidotic) to counteract ATOT
dilutional alkalosis
• Experimentally: SID 24 mEq/L
• E.g. Ringer’s lactate (SID=28), Hartmann’s (SID=27)
Morgan
TJ.
Crit
Care.
2005
Apr;9(2):204–11.

21. Calculating the Strong ion gap
• A- = albumin * constant + phosphate * constant
• SID = Na + K + Mg + Ca – Cl – A-
• SIG = SID – lactate – bicarb
• Anion gap = Na + K – Cl – bicarb – lactate
• AGc = AG / (2.5x reference albumin – pt albumin)

22. 5 Minutes of ICU Acid Base

23. Acidosis
• Sympathoadrenal activation
• Right-shift Hb dissociation
curve (+Haldane effect)
• Hyperkalemia (shift)
• SMC Cathecolamine
responsiveness decreases
Alkalosis
• Left-shift Hb dissociation
curve
• Hypocalcemia (plasma
protein binding)
- cardiac
- neuromuscular
• Reduced cerebral blood
flow
• Increased peripheral
vascular resistance
• Coronary vasospasm
• Bronchoconstriction
The physiological effects of pH changes
Morgan
&
Mikhail’s
Clinical
Anesthesiology
5e
(AccessMedicine)

24. Prognostic value
• Metabolic acidosis predicts mortality, lactate > other
causes
• Increased anion gap acidosis predicts morbidity &
mortality
• Metabolic acidosis = 2x mortality risk [adults]
• Hyperchloremic acidosis associated with ICU stay, renal
dysfunction, mortality [adults]
Lucking
SE,
Maffei
FA,
Tamburro
RF.
Pediatric
Cri-cal
Care
Study
Guide.
Springer;
2012.
Gunnerson
KJ,
Saul
M,
He
S,
Kellum
JA.
Crit
Care.
2006
Feb;10(1):R22.
McCluskey
SA,
Karou-
K,
Wijeysundera
D,
Minkovich
L,
Tait
G,
Beadle
WS.
Anesthesia
&
Analgesia.
2013
Nov
6.

25. Balasubramanyan N, Havens PL, Hoffman GM. Unmeasured
anions identified by the Fencl-Stewart method predict mortality
better than base excess, anion gap, and lactate in patients in
the pediatric intensive care unit. Critical Care Medicine. 1999
Aug 1;27(8):1577.
- n=255, retrospective cohort
- inclusion: PICU + acid base status measured
- ATOT determination superior to AG/BE/lactate for predicting
mortality
- Discussion: Possibly same with AGc ? Multiple
measurements, error
AGc
=
albumin
corrected
anion
gap

26. Dubin A, Menises MAM, Masevicius FD, Moseinco MC,
Kutscherauer DO, Ventrice E, et al. Comparison of three
different methods of evaluation of metabolic acid-base
disorders*. Critical Care Medicine. 2007 May;35(5):1264–70
- n=953, prospective observational cohort
- inclusion: ICU
- Stewart detected metabolic alterations in 14% of patients
with normal HCO3
- / BE
- SIG and AGc are correlated R2=.97
- Stewart and AGc perfomed as good in detecting metabolic
acidosis, and were superior to the traditional approach
SIG
=
strong
ion
gap
AGc
=
albumin
corrected
anion
gap

27. No Consequence for Clinical Practice ?
• Traditional approach is more intuitive and well known,
supported by robust experience and evidence
• Provision of clear epidemiological evidence for Steward
approached Dx / Tx is not given yet (sample size of
research…)
Rastegar
A.
Clinical
Journal
of
the
American
Society
of
Nephrology.
2009
Jul;4(7):1267–74.

28. 5 Minutes of Periop Cardio Acid/Base

29. Murray DM, Olhsson V, Fraser JI. Defining acidosis in
postoperative cardiac patients using Stewart’s method of strong
ion difference*. Pediatric Critical Care Medicine. 2004 May;5(3):
240–5.
- n=44, prospective
- inclusion: PICU post-cardiac Sx
- Daily acid-base status
- Metabolic acidosis: lactate, UA, SID
- CPB results in more SID acidosis
- Stewart detection of acids is superior: 13% of normal BE
samples had UA. However, AGc almost as good by ROC
AUC
UA
=
unmeasured
acids,
part
of
ATOT
AGc
=
albumin
corrected
anion
gap
ROC
AUC
=
receiver
operated
characteris-cs
area
under
the
curve

30. Hatherill M. Hyperchloraemic metabolic acidosis following open
cardiac surgery. Archives of Disease in Childhood. 2005 Dec
1;90(12):1288–92.
- n=97, prospective
- inclusion: PICU post-cardiac Sx
- Metabolic acidosis: lactate, UA, SID (less SID than Murray)
- No association with CPB time, ventilation, but complexity of
surgery
- No association with PICU length of stay
- Chloride from CPB priming / renal hypoperfusion?

31. Durward A, Tibby SM, Skellett S, Austin C, Anderson D,
Murdoch IA. The strong ion gap predicts mortality in children
following cardiopulmonary bypass surgery*. Pediatric Critical
Care Medicine. 2005 May;6(3):281–5.
- n=85, prospective
- inclusion: PICU post-cardiac Sx
- 41% (admission) and 52% (24h) raised strong ion gap
- SIG and lactate increased with surgical complexity, but not
length of CPB or aortic cross-clamping
- 5 deaths, 4 of which persistent SIG, 2 lactaemia

32. Mann C, Held U, Herzog S, Baenziger O. Impact of normal
saline infusion on postoperative metabolic acidosis. Pediatric
Anesthesia. 2009 Nov;19(11):1070–7.
- n=119, prospective
- inclusion: PICU post-cardiac Sx
- Intervals of Saline infusion / no saline infusion
- Saline infusion post-op is associated with metabolic acidosis
- This can be calculated by chloride effect of SID

33. WKZ PICU: 2 patient analyses
• pH, bicarbonate, PCO2, PO2, lactate, urea, ketones, Hb/
Ht, Na, K, phosphate, albumin, glucose, osmolality
• Pt A, pH 7.27 – mixed acidosis: low SID (high Cl),
increased ATOT (explained by lactate and ketones),
phosphate effect (high P). Alongside hypoalbuminemia
(metabolic alkalosis).
• Pt B, pH 7.23 – low SID acidosis (high Cl), phosphate
effect (high P)

34. Discussion Translation WKZ Practice

35. David Schmidt
d.e.schmidt@students.uu.nl

36. Figge-Fencl Stewart Modification
• Albumin charge is approximately linear over pH 6.9-7.9
• Can thus be calculated

37. Stewart modification
• Story DA. Strong ions, weak acids and base excess: a
simplified Fencl-Stewart approach to clinical acid-base
disorders. British Journal of Anaesthesia. 2004 Jan 1;92
(1):54–60.

38. The Scheingraber Gynecology Trial
• Two groups of 12 patients undergoing major
intraabdominal gynecologic surgery, saline or lactated
Ringer at 30ml / kg BW/h
• Saline caused metabolic acidosis with hyperchloremia
and SID decrease
• Infusion of both fluids results in hypoproteinemia and
decreased anion gap
• Authors consider condition benign, but argue for
treatment
• Complication of respiratory acidosis by opiate
analgesics ?
Scheingraber
et
al.
Anesthesiology.
1999
May;90(5):1265–70.
Prough
DS.
Anesthesiology.
1999
May;90(5):1247–9.

39. Further Repots Saline & Metabolic Acidosis
• Stephens RCM, Mythen MG. Saline-Based Fluids Can Cause a Significant Acidosis That
May Be Clinically Relevant. Critical Care Medicine. 2000 Sep 1;28(9):3375.
• Prough DS, Bidani A. Hyperchloremic metabolic acidosis is a predictable consequence of
intraoperative infusion of 0.9% saline. Anesthesiology. 1999 May;90(5):1247–9.
• Dorje P, Adhikary G, Tempe DK. Avoiding latrogenic hyperchloremic acidosis--call for a
new crystalloid fluid. Anesthesiology. 2000 Feb;92(2):625–6.
• Constable PD. Hyperchloremic Acidosis: The Classic Example of Strong Ion Acidosis.
Anesthesia & Analgesia. 2003 Apr;:919–22.
• Eisenhut M. Causes and effects of hyperchloremic acidosis. Crit Care. 2006;10(3):413;
authorreply413.