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 [email protected]

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A comprehensive initial evaluation of acid-base disorders in critical care medicine by strong ion difference and physicochemical analysis for housestaff rotating through the ICU Edward Omron MD, MPH, FCCP

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Page 1: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

[email protected]

Page 2: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 3: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

• Metabolic acid-base status

– What is it?

– Why is it important?

– Why assess for it?

– Can we do better?

Page 4: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 5: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

• Concept of pH

– pH H+

7.0 100 nmol/L

7.4 40

7.7 20

– pH = - log (H+): log linear

– Exponential in reality

Page 6: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

“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

Page 7: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 8: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 9: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 10: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 11: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 12: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 13: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

Law of Electrical NeutralityLaw of Electrical Neutrality

Cations Cations == AnionsAnions

Page 14: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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-

Page 15: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 16: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 17: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 18: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 19: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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/

Page 20: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 21: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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/

Page 22: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 23: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 24: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 25: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 26: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 27: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 28: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 29: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 30: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 31: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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)

Page 32: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

– 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

Page 33: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

• {+} 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

Page 34: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 35: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 36: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 37: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

• 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

Page 38: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 39: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

Treatment of Dehydration Versus Hypovolemia

Language Guiding Therapy: The Case of Dehydration versus Volume Depletion

Ann Intern Med 1997;127:848-853

Page 40: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 41: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 42: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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.

Page 43: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

• 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

Page 44: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 45: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 46: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 47: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 48: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 49: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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)

Page 50: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 51: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 52: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 53: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 54: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

• 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

Page 55: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

• 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

Page 56: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

Am J Respir Crit Care Med Vol 162. pp 2246–2251, 2000

Page 57: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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.

Page 58: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 59: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 60: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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-)

Page 61: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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-)

Page 62: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 63: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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)

Page 64: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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-

Page 65: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 66: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH
Page 67: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 68: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

Independent Determinants of pH

• Strong Ion Difference (SID)

• Strong Ion Gap

• Plasma Weak Acids

• CO2 production

• This is physico-chemical analysis!

Page 69: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 70: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 71: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 72: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 73: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 74: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 75: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 76: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 77: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 78: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 79: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 80: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

• 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

Page 81: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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 !

Page 82: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

Alkalosis activates PFK

**Aggravates lactic acidosis in shock states

Page 83: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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?

Page 84: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 85: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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?

Page 86: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 87: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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?

Page 88: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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

Page 89: Acid Base Disorders in Critical Care Medicine   Edward Omron MD, MPH

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.