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Acid Base Disorders in Critical Care Medicine Edward Omron MD, MPH
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Transcript of Acid Base Disorders in Critical Care Medicine Edward Omron MD, MPH
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Acid Base Disorders in the Intensive
Care Unit for Housestaff
Edward M. Omron MD, MPH, FCCP
Pulmonary and Critical Care Medicine
Morgan Hill, CA 95037
www.docomron.com
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OBJECTIVES
• A critical assessment of conventional acid-
base analysis
• A review of strong ion difference and
physicochemical analysis in acute illness
and major surgery
– Clinical applications in
• Electrolyte management
• Fluid resuscitation
• Complex acid-base disorders
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• Metabolic acid-base status
– What is it?
– Why is it important?
– Why assess for it?
– Can we do better?
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A 34-year-old white man presents with nausea, vomiting and has been
unable to consume any food or liquids. He admits to drinking about two pints
of vodka daily. Temperature is 99.6 F, pulse rate is 101 per minute supine and
126 per minute standing, respirations are 24 per minute, and blood pressure
is 110/85 mm Hg supine and 80/50 mm Hg when standing.
Sodium 134 mEq/L
Potassium 3.8 mEq/L
Chloride 83 mEq/L
Bicarbonate 24 mEq/L
PO2 89 mm Hg
PCO2 32 mm Hg
pH 7.48
Which of the following is the most likely explanation for these laboratory
findings?
(A) Respiratory alkalosis
(B) Respiratory alkalosis and metabolic acidosis
(C) Metabolic acidosis
(D) Respiratory alkalosis, metabolic acidosis, and metabolic alkalosis
(E) Metabolic alkalosis, respiratory alkalosis, and respiratory acidosis
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• Concept of pH
– pH H+
7.0 100 nmol/L
7.4 40
7.7 20
– pH = - log (H+): log linear
– Exponential in reality
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“The duty of the physician is to discover that
the quantity of sodium bicarbonate in the
blood is diminished, to restore that quantity
to normal, and to hold it there. But while
restoring it, he must never increase the
quantity above normal.”
Henderson LJ; Science 1917;46:73-83
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Figure 1. Henderson-Hasselbalch Equations
H+ + HCO3- H2CO3 CO2 + H2O
[H+] = 24 x PCO2/[HCO3-]
pH = 6.1 + Log [HCO3-] / [0.03 x PCO2]
pK = 6.1
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Slope Intercept H-H Equation
• y = mx + b
• Log [PCO2] = -1 (pH) + Log [HCO3-]/K
• In-vitro log PCO2- pH equilibration curve
– Linear relationship between log PCO2 and
pH
– Slope = -1
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Log PCOLog PCO22--pH Curve in PlasmapH Curve in Plasma
pH
Log P
CO
2K
P
Constable,P. J. Appl. Physiol. 1997; 83(1): 298
6.8 7.0 7.2 7.4 7.6 7.8 8.0 8.2
1.0
1.2
1.4
1.6
1.8
2.0
In-Vitro
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Log PCOLog PCO22--pH Curve in PlasmapH Curve in Plasma
pH
Log
pC
O2,
kP
asc
al
6.8 7.0 7.2 7.4 7.6 7.8 8.0 8.2
1.0
1.2
1.4
1.6
1.8
2.0Blue : in vitro
Green: in vivo
Crit Care Med 1998;26:1173-1179
Gibbs Donnan Effect
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Log PCOLog PCO22--pH Curve in PlasmapH Curve in Plasma
pH
Log P
CO
2,
kP
6.8 7.0 7.2 7.4 7.6 7.8 8.0 8.2
1.0
1.2
1.4
1.6
1.8
2.0
[Na+]
[Cl-]
Blue : in vitro
Green: in vivo
Red: Total Protein
Constable P. J Appl Physiol 1997; 83(1): 298
Gibbs Donnan Effect
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HH Equation
• Explains the effect of PCO2 on pH
– PCO2 directly measured
– Linear relationship between pH and PCO2
• HH does not explain the effects of:
– Na+ (Hypernatremia, Hyponatremia)
– Cl- (Hypochloremia, Hyperchloremia)
– Unmeasured and measured anions and cations
• lactate, ketones, salicylates, lithium, serum globulins …
– hypoalbuminemia and hyperphosphatemia
– Resuscitation Fluids
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Law of Electrical NeutralityLaw of Electrical Neutrality
Cations Cations == AnionsAnions
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Plasma Strong IonsPlasma Strong Ions
• Strong cations and anions
– Na+, K+, Ca++, Mg++, Cl-, Lactate-
– Fully dissociated, exert no buffering effect
– Combined positive electrical effect
• Strong Ion Difference (SID)
– Collective unit of charge (mEq/L)
– Strong cations - anions
• Na++K++Ca+++Mg++-Cl- - lactate = +39 mEq/L
– Approximated by difference between Na+ and Cl-
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20
40
60
80
100
120
140
160
mm
ol/
L
Cations Anions
Na+ = 142
K+ Ca++ Mg++
Cl- = -106
0
SID = +39
Charge Balance at Standard Physiologic State
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20
40
60
80
100
120
140
160
mE
q/L
Cations Anions
Na+ = 142
K+ Ca++ Mg++
Cl- = -106
HCO3 = -24.6
A- = -14.4
0
Buffer Base = -39 SID = +39
pH = 7.40
PaCO2 = 40 mm Hg
BEp = 0 mEq/L
SBE = 0 mEq/L
ANG = 12 mEq/L
SIG = 5 mEq/L
Charge Balance at Standard Physiologic State
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Strong Ions and Charge Balance
Na+ + K+ + Mg++ + Ca++ + H+ = Cl- + HCO3- + OH- + lactate- + A- + XA- + Pi-
Na+ + K+ + Mg++ + Ca++ - Cl- - lactate- - XA- = HCO3- + A- + Pi-
(Na+ + K+ + Mg++ + Ca++ - Cl- - lactate- - XA-) = (HCO3- + A- + Pi-)
+39 = ?-39
Strong Ion Difference = Buffer Base
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Plasma Buffer Base
• Weak acids: pKa 5.8-8.9
• Volatile buffer anion bicarbonate
– HCO3- + H+ = H2CO3 = CO2 + H2O
– Open buffer system in plasma
• Nonvolatile Buffer Anions
– Albumin (imidazole amino protein groups)
– Inorganic Phosphorus (PI): H2PO42-
– Total Citrate
J Appl Physiol 1986; 61: 2260-2265
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Plasma Buffer Base (BB)Plasma Buffer Base (BB)
• Total buffer capacity of plasma
– [HCO3-] - 24.6 mEq/L
– [Alb] + [PI] +[Citrate] - 14.4 mEq/L
NORMAL = - 39 mEq/L
http;/www.Figge-Fencl.org/
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Standard physiological state in plasma for 70 kg test
subject (TBW = 60% total body weight)
SID, strong ion difference; Atot, plasma nonvolatile weak acid buffer content; SBE, standard
base excess; HCO3, bicarbonate; TBW, total body water; ECV, extracellular compartment
volume; PV, plasma volume
pH Regulating
Variables
Derived
Parameters
SID (mEq/L) 39 Weight (Kg) 70.0 pH 7.400
PCO2 (mm Hg) 40.0 TBW (L) 42.0 [HCO3]HH (mEq/L) 24.6
Atot ECV (L) 14.0 SBE (mEq/L) 0.2
Albumin (g/dL) 4.40 PV (L) 3.5
Phosphate (mmol/L) 1.16
Citrate total (mmol/L) 0.135
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Calculation of the SID or Buffer Base
• Buffer Base [HCO3-] + 2.8 x [Alb-] g/dL + 0.6 x [Pi] mg/dL
– BB = -24.6 mEq/L- 2.8 x 4.4 g/dL – 0.6 x (3.6 mg/dL)= -39
• Figge-Fencl algorithm
– http://www.figge-fencl.org/
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Δ SID Δ buffer base
• A change in SID forces a change in buffer
base
• Displacement from normal (+39 mEq/L)
quantitates metabolic acid-base disorders
• PCO2 independent index
Singer RB, Hastings AB. Medicine 1948; 27: 223-242
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20
40
60
80
100
120
140
160 m
Eq
/L
Cations Anions
Na+ = 142
K+ Ca++ Mg++
Cl- = -116
HCO3 = -15.8
A- = -13.2
0
Buffer Base = -29 SID = +29
( 10)
pH = 7.209
PCO2 = 40 mm Hg
BEp = -10 mE/L
SBE = -11 mEq/L
ANG = 11 mEq/L
SIG = 5 mEq/L
Hyperchloremic Metabolic Acidosis
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Buffer Base (BB) in Hyperchloremia
HCO3- = - 24.6 mEq/L
Albumin +PI = -14.4 mEq/L
HCO3- = -15.8
Albumin + PI = -13.2
BB = -39 mEq/L and
BB = -29 mEq/L and Cl- = 116
H+ +HCO3- H2CO3 CO2 +H2O
BEp = -10 mEq/L
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20
40
60
80
100
120
140
160
mm
ol/
L
Cations Anions
Na+ = 142
K+ Ca++ Mg++
Cl- = -106
HCO3- = -15.8
Alb- + PI = -13.2
0
Buffer Base = -29 SID = +29
Lactic Acidosis (Lactate- = 10 mmol/L)
pH = 7.208
PCO2 = 40 mm Hg
BEp = -10 mmol/L
Lac- = -10
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20
40
60
80
100
120
140
160
mm
ol/
L
Cations Anions
Na+ = 142
K+ Ca++ Mg++
Cl- = -106
HCO3- = -15.8
Alb- + PI = -13.2
0
Buffer Base = -29 SID = +29
Ketoacidosis (Ketones- = 10 mmol/L)
pH = 7.208
PCO2 = 40 mm Hg
BEp = -10 mmol/L
Ket- = -10
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20
40
60
80
100
120
140
160
mm
ol/
L
Cations Anions
Na+ = 142
K+ Ca++ Mg++
Cl- = -116
HCO3- = -15.8
Alb- + PI = -13.2
0
Buffer Base = -29 SID = +29
Hyperchloremic Phase of DKA
( 10)
pH = 7.208
PCO2 = 40 mm Hg
BEp = -10 mmol/L
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20
40
60
80
100
120
140
160 m
Eq
/L
Cations Anions
Na+ = 142
K+ Ca++ Mg++
Cl- = -96
HCO3 = -33.8
A- = -15.2
0
Buffer Base = - 49 SID = +49
( 10)
pH = 7.54
PCO2 = 40 mm Hg
BEp = 10 mEq/L
SBE = 11 mEq/L
ANG = 13
Hypochloremic Metabolic Alkalosis
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6.8
6.9
7
7.1
7.2
7.3
7.4
7.5
7.6
15 20 25 30 35 40 45 50 55
pH
SID (mEq/L)
pH = 7.4
PaCO2 = 40 mm Hg
SID = 39 mEq/L
AT = Standard State
+ -
pH as a function of SID
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Etiology of Metabolic Acid-Base
Disturbances
• Changes in Strong Ion Difference
– Increased = Metabolic Alkalosis
• Excess of plasma cations
– Reduced = Metabolic Acidosis
• Excess of plasma anions
*Summarizes Acid-Base Status Circa 1962
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Plasma Base Excess
0
10
20
30
40
50
60
70
80
90
-20 -15 -10 -5 0 5 10 15 20 25
Plasma Base Excess (mEq/L)H
+ (
nM
/L)
*Summarizes Acid-Base Status Circa 1962
24 29 34 39 44 49 54
SID (mEq/L)
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– Excess Anions < -2 mMol/L (Metabolic Acidosis)
– Excess Cations > +2 mMol/L (Metabolic Alkalosis)
– Change from 39 reflects of degree of anion /
cation disparity only regarding strong ions
– Magnitude of metabolic component of acid-base
status in plasma compartment
• Not Standard Base Excess (SBE)
– PCO2 independent index
BE Scale for Metabolic Acid-Base Disorders
*Siggard-Anderson O. Scand J Clin Lab Invest 1962; 14: 598-604
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• {+} value
• excess plasma cations = metabolic alkalosis
• {-} value
• excess plasma anions = metabolic acidosis
• Magnitude of metabolic component of acid-base
status in extracellular fluid compartment
• Adjusts for Gibbs Donnan effect unlike BEp
• Metabolic Acidosis
• PCO2 = SBE then normal compensation
• Respiratory acidosis/alkalosis (pure)
• SBE = 0
• PCO2 independent index
Standard Base Excess
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Which profile has the most severe
metabolic acid-base derangement?
• A. pH = 7.19, PCO2 = 40, HCO3 = 15
• B. pH = 7.55, PCO2 = 18, HCO3 = 15
• C. pH = 7.10, PCO2 = 74, HCO3 = 22
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Which profile has the most severe
metabolic acid-base derangement?
• A. pH = 7.19, PCO2 = 40, HCO3 = 15
– SBE = -11.6 mmol/L
• B. pH = 7.55, PCO2 = 18, HCO3 = 15
– SBE = -6.6 mmol/L
• C. pH = 7.10, PCO2 = 74, HCO3 = 22
– SBE = -6.4 mmol/L
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Dehydration
• Dehydration and Water intoxication – Water loss/gain from intracellular and interstitial
compartments
– Associated with hypertonicity/hypotonicity and changes in plasma [Na+] (excludes uremia, DKA, NKHC, mannitol…)
– Symptoms: thirst, confusion, coma
– Quantitatively described as free water deficiency /excess
• Volume of water that must be removed/added to hypotonic/hypertonic plasma to make isotonic plasma
– Treatment: D5W with electrolytes, diuretics, and hypertonic saline
Language Guiding Therapy: The Case of Dehydration versus Volume Depletion
Ann Intern Med 1997;127:848-853
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• Volume depletion/expansion (hypo and hypervolemia)
– Extracellular fluid compartment volume depletion/excess that affects the vascular tree
– Surrogate term for where cardiac function lies on the Starling Curve
– Diagnosis: • Macrocirculation Impairment: BP, HR, Orthostatics
• Microcirculation Impairment: Lactic Acidosis, Low venous Svo2
– Treatment: Crystalloids, Colloids, PRBC, or diuretics
Volume Depletion
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Dehydration versus Volume Depletion
• Changes in extracellular and intracellular compartment volumes can be and often are dissociated
• Indiscriminate use of the terms dehydration and volume depletion risks confusion and therapeutic errors
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Treatment of Dehydration Versus Hypovolemia
Language Guiding Therapy: The Case of Dehydration versus Volume Depletion
Ann Intern Med 1997;127:848-853
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Free Water Excess/Deficit effects on [Cl-]
• Free H2O abnormality detected as an abnormal [Na+]
– Plasma [Cl-] has to be corrected for the dilution or concentration of plasma [Na+]
– [Cl-] predicted = [Cl-] normal x [Na+] observed / [Na+] normal
– If plasma [Na+] =155 mmol/L
• Then [Cl-] = 106 x 155/142 = 115 mmol/L
– If plasma [Na+] =131 mmol/L
• Then [Cl-] = 106 x 131/142 = 97 mmol/L
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Free H2O excess/deficit effects on Plasma [Na+]
-3 L 155 115 +3 (42)
-2 L 150 111 +2 (41)
-1 L 146 108 +1 (40)
0 142 105 0 (39)
+1 L 138 102 -1 (38)
+2 L 134 99 -2 (37)
+3 L 131 97 -3 (36)
Free H2O [Na+] [Cl-] SID/SID
Standard State
Nguyen M. and Kurtz I: J Applied Physiology 2006; 100: 1293–1300
Concentr
ational
Alk
alo
sis
D
ilutional A
cid
osis
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Sodium 134 mEq/L
Potassium 3.8 mEq/L
Chloride 83 mEq/L
Bicarbonate 24 mEq/L
PO2 89 mm Hg
PCO2 32 mm Hg
pH 7.48
Which of the following is the most likely explanation for these laboratory
findings?
(A) Respiratory alkalosis
(B) Respiratory alkalosis and metabolic acidosis
(C) Metabolic acidosis
(D) Respiratory alkalosis, metabolic acidosis, and metabolic alkalosis
(E) Metabolic alkalosis, respiratory alkalosis, and respiratory acidosis
Cl-(corrected) =106 x 134/142
=100 mEq/L
Cl-(observed) = 83 mEq/L
17 mEq/L excess cations
BEp = +17 strong cations
ANGcorr = 33 or -17 anions
A 34-year-old white man presents with nausea, vomiting and has been unable to
consume any food or liquids. He admits to drinking about two pints of vodka daily.
Temperature is 99.6 F, pulse rate is 101 per minute supine and 126 per minute
standing, respirations are 24 per minute, and blood pressure is 110/85 mm Hg
supine and 80/50 mm Hg when standing.
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• Changes in Strong Ion Difference – Increased = Metabolic Alkalosis
• Excess of plasma cations
– Reduced = Metabolic Acidosis • Excess of plasma anions
• Water deficit/excess: • Hypernatremia = Alkalosis (Cation Excess)
• Hyponatremia = Acidosis (Cation Deficient)
• Cation/Anion Imbalance • Hypochloremia = alkalosis (Anion Deficient)
• Hyperchloremia = acidosis (Anion Excess)
• Organic Acids (lactate, Ketones…) = acidosis – Anion Excess
Etiology of Metabolic Acid-Base Disturbances
*Summarizes Acid-Base Status Circa 1962
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20
40
60
80
100
120
140
160
mm
ol/
L
Cations Anions
Na+ = 142
K+ Ca++ Mg++
Cl- = -106
HCO3- = -24.6
Alb- + PI = -14.4
0
Buffer Base = -39 SID = +39
Standard Physiologic State [Pi] = 3.6 mg/dL
pH = 7.40
PCO2 = 40 mm Hg
BEp = 0 mEq/L
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20
40
60
80
100
120
140
160
mm
ol/
L
Cations Anions
Na+ = 142
K+ Ca++ Mg++
Cl- = -106
HCO3- = -21.2
Alb- + PI = -17.8
0
Buffer Base = -39 SID = +39
Hyperphosphatemic Metabolic Acidosis
[Pi] = 10 mg/dL
pH = 7.337
PCO2 = 40 mm Hg
BEp = -3.7 mEq/L
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20
40
60
80
100
120
140
160 m
Eq
/L
Cations Anions
Na+ = 142
K+ Ca++ Mg++
Cl- = -106
HCO3- = - 36.3
A- = - 2.7
0
Buffer Base = -39 SID = +39
Standard State Acid Base Status
[Alb-] = 0 mg/dL
pH = 7.571
PCO2 = 40 mm Hg
BEp = 13 mEq/L
SBE = 13 mEq/L
ANG = 1
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pH As A Function of Serum Albumin
Concentration
7.35
7.4
7.45
7.5
7.55
1 1.5 2 2.5 3 3.5 4 4.5 5
Albumin (g/dL)
pH
FIXED
SID = 39 mEq/L
PCO2 = 40 mm Hg
Phosphate = 3.6 mg/dL
Fencl V, Rossing TH. Ann Rev Med 1989; 40:17-29
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Hyperchloremic Acidosis
[Alb-] = 4.4 gm/dL
20
40
60
80
100
120
140
160
mm
ol/
L
Cations Anions
Na+ = 142
K+ Ca++ Mg++
Cl- = -115
HCO3- = - 15.8
Alb- + PI = - 13.2
0
Buffer Base = -29 SID = +29
( 10)
pH = 7.208
PCO2 = 40 mm Hg
BEp = -10 mEq/L
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20
40
60
80
100
120
140
160
mE
q/L
Cations Anions
Na+ = 142
K+ Ca++ Mg++
Cl- = -116
HCO3 = - 21.2
A- = - 7.8
0
Buffer Base = -29 SID = +29
( 10)
pH = 7.338
PCO2 = 40 mm Hg
SBE = - 4 mEq/L
ANG = 6 mEq/L
Adj. ANG = 12 mEq/L
SIG = 5 mEq/L
Hyperchloremic strong ion acidosis with concurrent
hypoalbuminemic alkalosis ([albumin] = 2g/dL)
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Hypoalbuminemic Alkalosis
HCO3- = -15.8 mEq/L
Charge =
-13.2 mEq/L
HCO3- = -21.2 mEq/L
Albumin
2.0 g/dL
BB = -29 BB = -29
H+ +HCO3- H2CO3 CO2 +H2O
Albumin
4.4 g/dL Charge =
-7.8 mEq/L
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Hypoalbuminemia- an adaptive response
• Hypoalbuminemia independent risk factor
• Beneficial by restoring pH towards normal
• SBE = -10 mmol/L (Lactate = 10 mmol/L)
[Albumin-] = 4.4 g/dL, pH = 7.20
2.2 g/dL, pH = 7.33
1.1 g/dL, pH = 7.38
J Appl Physiol 1986; 61: 2260-2265
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pH as a Function of [Alb] and SID
6.8
7
7.2
7.4
7.6
15 20 25 30 35 40 45 50 55
SID (mEq/L)
pH
1.1 2.2 4.4Albumin (g/dL) =
7.20
7.33
7.38
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AlbuminAlbumin
• Major nonvolatile plasma weak acid buffer
– (4 - 4.4 g/dL in plasma)
• 1 gm = 2.8 mEq of acid
• Accounts for 12.5 mEq/L of plasma fixed acid
– Hypoalbuminemia = alkalosis
– Hyperalbuminemia = acidosis
– Loss of weak acid = gain in basic equivalents
J Appl Physiol 1986; 61: 2260-2265
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• Hypoalbuminemia pervasive in acute illness
and surgery
• Hypoalbuminemic alkalosis exists to some
extent in all critically ill patients
• Hypoalbuminemia corrects pH towards
standard state in acute illness
Am J Respir Crit Care Med 2000; 162: 2246-2251
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• Changes in Strong Ion Difference – Increased = Metabolic Alkalosis
• Excess of plasma cations
– Reduced = Metabolic Acidosis • Excess of plasma anions
• Water deficit/excess: • Hypernatremia = Alkalosis (Cation Excess)
• Hyponatremia = Acidosis (Cation Deficient)
• Cation/Anion Imbalance • Hypochloremia = alkalosis (Anion Deficient)
• Hyperchloremia = acidosis (Anion Excess)
• Organic Acids (lactate, Ketones…) = acidosis – Anion Excess
• Abnormal concentrations of plasma weak acids – Independent determinants of pH
– Hypoalbuminemia = metabolic alkalosis
– Hyperalbuminemia = metabolic acidosis
– Hyperphosphatemia = metabolic acidosis
Etiology of Metabolic Acid-Base
Disturbances
*Summarizes Acid-Base Status Circa 1982
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Am J Respir Crit Care Med Vol 162. pp 2246–2251, 2000
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Anion Gap (1977)
• Law of electrical neutrality
– Discrepancy between cations and anions virtual
– Na+ + K+ = Cl- + HCO3- + XA-
– (Na+ + K+ - Cl- - HCO3) 16
– Facilitates differential diagnosis (easy to compute)
– Normal ANG entirely accounted for by [albumin] + PI
– ANG = 2.8*Albumin + 0.5 *PI
– Very Unreliable in critical illness
• Hypoalbuminemia
• pH changes
• Gibbs Donnan Effect
Oh MS & Carroll HJ. The Anion Gap. NEJM 1977; 297: 814-817.
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20
40
60
80
100
120
140
160 m
Eq
/L
Cations Anions
Na+ = 142
K+ = 4
Cl- = -105
HCO3 = -24.6
A- = -14.4
0
pH = 7.40
PCO2 = 40 mm Hg
SBE = 0 mEq/L
ANG = 12 mEq/L
SIG = 5 mEq/L
XA-
XA- = Unmeasured Anions:
Cyanide
Glycols
Iron
Isoniazid
Ketoacids
Krebs Cycle
Lactate
Methanol
Paraldehyde
Toluene
Salicylate
Uremia
ANG
Anion Gap
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68 yo male UGI Bleed
Na =132, K = 4, Cl = 98, HCO3 = 22
Lactate = 4.5, Alb = 2.8
ANG = Na + K – Cl – HCO3 = 16 (“normal”)
ANG(c) = 16 + 2.8(4.4 - 2.8) = 20.5 (abnormal)
WHY? Adding back lost charge from hypoalbuminemia
Anion gap and hypoalbuminemia. Crit Care Med. 1998 Nov;26(11):1807–1810
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Anion Gap as function of Albumin
Concentration
4
6
8
10
12
14
16
1 1.5 2 2.5 3 3.5 4 4.5 5
Albumin (g/dL)
An
ion
Ga
p (
mE
q/L
)
Fencl V, Rossing TH. Ann Rev Med 1989; 40:17-29
Anion Gap = ( Na+ + K+ – Cl- – HCO3-)
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Anion Gap as a function of pH
11
12
13
14
15
16
6.8 7 7.2 7.4 7.6
pH
An
ion
Gap
Anion Gap = ( Na+ + K+ – Cl- – HCO3-)
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Anion GapAnion Gap
• Insensitive index of organic acidosis in acute
illness and post surgery (hypoalbuminemia, pH
effects)
• Adjusted Anion Gap for hypoalbuminemia
= ANG + 2.8( 4.4 - Observed alb.)
Increased anion gap = acidosis
Decreased anion gap = alkalosis
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Strong Ion Gap
• Unmeasured Anions of Critical Illness
– All organic anions (ketones, lactate …)
• Codeterminants of Strong Ion Difference
– SIG = SID(apparent) – Buffer Base
– SIDa = Na+ + K+ +Ca+++ Mg++ - Cl- - Lactate-
• Not affected by pH or [Albumin]
• Equivalent to the Anion Gap (corrected)
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20
40
60
80
100
120
140
mm
ol/
L
Cations Anions
Na+ = 142 Cl- = -106
HCO3- = -24.6
Alb- + PI = -14.4
0
Strong Ion Gap: SIDa – BB = SIG
pH = 7.40
PCO2 = 40 mm Hg
BEp = 0 mmol/L
XA- K+ Ca2+ Mg2+
Lactate-
SIDa Buffer Base
Strong Ion Gap
SIDa = Na+ + K+ + Ca2+ + Mg2+ - Cl- - lactate- - XA-
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20
40
60
80
100
120
140
160 m
Eq
/L
Cations Anions
Na+ = 142
K+ = 4
Cl- = -105
HCO3
A-
0
pH = 7.40
PCO2 = 40 mm Hg
SBE = 0 mEq/L
ANG = 12 mEq/L
SIG = 5 mEq/L
XA-
SIDa
Strong Ion Gap
SIDe or Buffer Base
Strong Ion Gap
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Calculation of the SID and apparent SID
• Buffer Base [HCO3-] + 2.8 x [Alb-] g/dL + 0.6 x [Pi] mg/dL
– BB = -24.6 mEq/L- 2.8 x 4.4 g/dL – 0.6 x (3.6 mg/dL)= -39
• SIDa Na+ + K+ + (Mg2+ + Ca 2+) - Cl- - lactate-
– SIDa Na+ + K+ + 3 – Cl- - lactate- = 42 mEq/L
• SIG = SIDa – Buffer Base
• SIG = 42 – 39 3 mEq/L
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Independent Determinants of pH
• Strong Ion Difference (SID)
• Strong Ion Gap
• Plasma Weak Acids
• CO2 production
• This is physico-chemical analysis!
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Physico-Chemical Analysis
• Three independent determinants of acid-base
status
– Strong Ion Difference
– PCO2
– Variable weak acid total ([albumin-] + PI)
• Mechanistic and quantitative
• Guides diagnosis and therapy
Stewart P. Can J. Physiol. Pharmacology 1983; 61: 1444-1461
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Normal Saline Lactated Ringer's 1/2 NS with 75 mEq/L NaHCO3 NaHCO3
Na 154 130 150 150
K 4
Mg
Ca 3
Cl 154 109 75
Acetate
Gluconate
Lactate 28
SID 0 28 75 150
*Caution must be exercised in patients with acute or chronic renal failure
and K containing solutions (LR)
*NaHCO3 solution: 3 Amps NaHCO3 in 1 Liter sterile water or D5W
Isotonic Crystalloid Solutions
-1.8 SBE/L +0.4 SBE/L +4 SBE/L +9 SBE/L
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Crystalloid SID and serum [HCO3-]
• If crystalloid SID plasma [HCO3-] (24.6 mmol/L)
– No change in SBE or acid-base status
– Lactated Ringer’s, Hartman’s Solution, Hextend
• If crystalloid SID < plasma [HCO3-]
– Metabolic acidosis
– Normal Saline
• If crystalloid SID > plasma [HCO3-]
– Metabolic alkalosis
– Plasmalyte, ½ NS + 75 mEq/L NaHCO3, and isotonic
bicarbonate solutions
Omron E: J Int Care Med 2010. 25; 271-280
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Metabolic Acid-Base Effects of Crystalloid Infusion
-15
-10
-5
0
5
10
15
20
25
30
35
40
0 1 2 3 4 5 6 7 8 9 10
Crystalloid Infusion Volume (Liters)
SB
E m
Eq
/L
Normal Saline (SID = 0)
Crystalloid SID = 24.5 mEq/L
Ringer's Lactate (SID = 28)
Plasmalyte 148 (SID = 50)
1/2 NS + 75 mEq/L NaHCO3 (SID = 75)
0.15 M NaHCO3 (SID = 150)
Omron E: J Int Care Med 2010. 25; 271-280
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Physicochemical Resuscitation
• Principles – Patients in shock with a metabolic acidosis are
optimally managed with isotonic crystalloid
solutions that are alkaline when infused
– Patients with normal acid base status are best
managed with isotonic balanced solutions
– Patients with metabolic alkalosis are optimally
managed with isotonic solutions that are acidic
when infused
– The principles of Early Goal Directed Therapy are
to be done concurrently with physicochemical
resuscitation
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Crystalloid Resuscitation Guidelines at albumin = 2.2 g/dL
0
10
20
30
40
50
60
70
80
90
-20 -15 -10 -5 0 5 10 15 20 25
SBE (mEq/L)
H+
(n
M/L
)
0** 3 4 4 0** 0** 1** 2 1
0 = HCl infusion (0.1 N) at 100 to 200 cc/ hr, central access (SID = -100), 3 mmol/L acid
1 = Normal Saline (SID = 0), 1.8 mmol/L acid
2 = Lactated Ringers ( SID = 28), 0.4 mmol/L base
3 = ½ NS with 75 mEq/L NaHCO3 in 1 liter (SID = +75), 4 mmol/L base
4 = 3 Amps NaHCO3 in sterile H20 in 1 liter (SID = +150), 9 mmol/L base Edward Omron MD, MPH
** Acetazolamide 250 mg IVP q12, no more than 500 mg qday Pulmonary / Critical Care
Dialysis
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Isotonic (Normal) Saline
• 0.9% Sodium Chloride in sterile water
• Na+ = 154 mmol/L, Cl- = 154 mmol/L
• SID = 0
• Excellent choice in
– Hypovolemic, Hypochloremia with metabolic alkalosis
– SBE ≥ 0
• 1.8 mmol/L fixed acid generated (excess Cl-)
• -1.8 SBE/Liter infused
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Lactated Ringer’s Solution
• Polyionic isotonic crystalloid that mimics plasma
electrolyte concentration
• Na+ = 130, K+=4, Cl- = 109, Lact- = 28, Ca++ = 3
• SID = 28
• Excellent choice in mild metabolic acidosis with
preserved renal function (SBE = -5 to +5)
• 0.4 mmol/L fixed base
• 0.4 SBE/Liter infused
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1/2 NS with 75 mEq/L HCO3
• 1/2 NS + 1.5 Amps Na HCO3 per liter
• Isotonic resuscitation and maintenance
• Na+ =150 mmol/L, Cl- = 75 mmol/L HCO3 = 75
mmol/L
• SID = +75
• Hyperchloremic metabolic acidosis and reduced
renal function Plasma SBE -10 to -5
• 4 mmol fixed base/Liter infused
• +4 SBE/ Liter
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Isotonic NaHCO3- Administration
• 3 Amps Na HCO3 in 1 liter sterile H2O
• Isotonic Resuscitation and maintenance
• Na+ = 150, HCO3 = 150
• SID = 150
• Excellent choice in malignant acidemias
• Bridge to acute dialysis: SBE ≤ -10
• +9 mmol fixed base/ Liter infused
• +9 SBE/Liter
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Metabolic Acid-Base Effects of Crystalloid Infusion
during moderate metabolic acidosis
-15
-10
-5
0
5
10
15
0 1 2 3 4 5
Crystalloid Infusion Volume (Liters)
SB
E m
Eq
/L
Normal Saline
Crystalloid SID = 20 mEq/L
Ringer's Lactate
Plasmalyte
1/2 NS + 75 mEq/L NaHCO3
0.15 M NaHCO3
Omron E: J Int Care Med 2010. 25; 271-280
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• Assumptions
– Normal renal function
– Acute and chronic kidney injury result
in marked impairment in chloride
excretion
– VD may change in acute illness and
surgery
– Ignores the effects of tissue buffering
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Bicarbonate Solutions
• Historically: hyperosmolar solution – 1 amp = 50 mEq/50 cc or 1 mEq/cc (1 M)
– Correction of extracellular acidosis at the expense of massive intracellular derangement
– No defined physico-chemical endpoint
– Hypertonic volume expansion • Recently shown to increase mortality in shock
– Only use isotonic solutions: Sterile water or D5W + 3 amps Na HCO3! (0.15 M)
– Activates Phosphofructokinase !
– Aggravates minute ventilation !
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Alkalosis activates PFK
**Aggravates lactic acidosis in shock states
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28 yo male with ARDS undergoing
diuresis
• pH = 7.61, PaCO2 = 40 mm Hg,
• [HCO3-]HH = 39.4 mmol/L,
• SBE = 16.8 mmol/L
• Na+ = 144 mmol/L, Cl- = 91 mmol/L
• Cl- corrected = 106 x 144/142 = 107
– Cl- loss 16 mmol/L ( 107-91) = 16 mmol/L excess cations
• Severe hypochloremic metabolic alkalosis
– Mechanism?
– Treatment?
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Crystalloid Resuscitation Guidelines at albumin = 2.2 g/dL
0
10
20
30
40
50
60
70
80
90
-20 -15 -10 -5 0 5 10 15 20 25
SBE (mEq/L)
H+
(n
M/L
)
0** 3 4 4 0** 0** 1** 2 1
0 = HCl infusion (0.1 N) at 100 to 200 cc/ hr, central access (SID = -100), 3 mmol/L acid
1 = Normal Saline (SID = 0), 1.8 mmol/L acid
2 = Lactated Ringer’s( SID = 28), 0.4 mmol/L base
3 = ½ NS with 75 mEq/L NaHCO3 in 1 liter (SID = +75), 4 mmol/L base
4 = 3 Amps NaHCO3 in sterile H20 in 1 liter (SID = +150), 9 mmol/L base Edward Omron MD, MPH
** Acetazolamide 250 mg IVP q12, no more than 500 mg qd Pulmonary / Critical Care
Dialysis
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67 yo female with ischemic bowel
• BP 80/40, HR 120, HCT= 25
• pH = 7.26, PaCO2 = 24, HCO3 = 11,
• SBE = -14.6
• Na+ = 143, Cl- = 118
• Cl- corrected = 106 x 143/142 106
• Excess Cl- (118 - 106) = 12 mmol/L
• Mechanism: Hyperchloremia
• How do you fix?
What are the resuscitation fluids of choice?
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Crystalloid Resuscitation Guidelines at albumin = 2.2 g/dL
0
10
20
30
40
50
60
70
80
90
-20 -15 -10 -5 0 5 10 15 20 25
SBE (mEq/L)
H+
(n
M/L
)
0** 3 4 4 0** 0** 1** 2 1
0 = HCl infusion (0.1 N) at 100 to 200 cc/ hr, central access (SID = -100), 3 mmol/L acid
1 = Normal Saline (SID = 0), 1.8 mmol/L acid
2 = Lactated Ringer’s( SID = 28), 0.4 mmol/L base
3 = ½ NS with 75 mEq/L NaHCO3 in 1 liter (SID = +75), 4 mmol/L base
4 = 3 Amps NaHCO3 in sterile H20 in 1 liter (SID = +150), 9 mmol/L base Edward Omron MD, MPH
** Acetazolamide 250 mg IVP q12, no more than 500 mg qd Pulmonary / Critical Care
Dialysis
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78 yo with severe pneumonia and
sepsis
• pH=7.37, PCO2=26.9, HCO3=15.2,
• SBE = -9,
• Na = 134 and Cl = 113 and albumin = 3 g/dL
• Cl- corrected = 106 x 134/142 = 100 mmol/L – Excess chloride = 13 mmol/L
• Mechanism of metabolic acidosis
– Hyperchloremia
– Free water excess reducing Na
• Hypoalbuminemic Alkalosis • How do you fix?
• Resuscitation Fluid?
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Crystalloid Resuscitation Guidelines at albumin = 2.2 g/dL
0
10
20
30
40
50
60
70
80
90
-20 -15 -10 -5 0 5 10 15 20 25
SBE (mEq/L)
H+
(n
M/L
)
0** 3 4 4 0** 0** 1** 2 1
0 = HCl infusion (0.1 N) at 100 to 200 cc/ hr, central access (SID = -100), 3 mmol/L acid
1 = Normal Saline (SID = 0), 1.8 mmol/L acid
2 = Lactated Ringer’s( SID = 28), 0.4 mmol/L base
3 = ½ NS with 75 mEq/L NaHCO3 in 1 liter (SID = +75), 4 mmol/L base
4 = 3 Amps NaHCO3 in sterile H20 in 1 liter (SID = +150), 9 mmol/L base Edward Omron MD, MPH
** Acetazolamide 250 mg IVP q12, no more than 500 mg qd Pulmonary / Critical Care
Dialysis
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Additional References
http://www.slideshare.net/edofiron
www.acidbase.org
http://www.figge-fencl.org/
Intensive Care Medicine 2011. 37; 461-468.
J. Intensive Care Medicine 2010. 25; 271-280.
Intensive Care Medicine 2009. 35; 1377-1382.
Critical Care Medicine 2005. 21; 329-346.
Best Practice Res Clin Anes 2004. 18; 113-127.
Kidney Inter. 2003. 64; 777-787.
Am. J. Respir. Crit. Care Med. 2000. 162; 2246-2251.
J. Applied Physiology 1999. 86; 326-334.
Annual Review Medicine 1989. 40; 17-29.