Dave StoryMBBS, MD, BMedSci, FANZCA

Professor and Chair of AnaesthesiaHead of Anaesthesia, Perioperative and Pain Medicine Unit (APPMU)

Melbourne Medical SchoolThe University of Melbourne

The Meaning of Acidosis?

Conflict of Interest

I think I have no conflict of interest associated with this presentation

The OED

Acid: from “acidus”, Latin: “sour” 1625

Boswell: “Rather an acid expression

of countenance”

Definitions of acid

Like other definitions “sour” is still used today

in parallel with other acid definitions

Depends on context

Strong ion acidosis- Stewart

Bicarbonate and hydrogen ions dependent factors

Bicarbonate is a marker not a mechanism

Base-excess is a marker

Sirker et al. Anaesthesia, 2002Miller’s Anesthesia

H+ / HCO3

CO2

SID

Weak acids

Kw + Ka

Definitions of acid

Faraday, 1830s

English electrochemist,

-metal ions (sodium): base forming

-ions like chloride: acid forming

Definitions of acid

Arrhenius, 1870s

Swedish Chemist

• Electrolytic theory for ions

(Almost failed PhD but later Nobel Prize)

• First suggested CO2 greenhouse effect

General acid definition:

Substance that increases [H+]

when added to a solution

The next step

Naunyn, 1890s

German Diabetes physician Combined Arrhenius definition of acid with Faraday’s ideas:

plasma acid-base status partly determined by electrolytes -particularly sodium and chloride

Henderson and Hasselbalch

Henderson, 1908Boston Physician

H+ = Ka X [H2CO3] [NaHCO3]

Henderson, Am J Phys, 1908

Hasselbalch, 1916Danish gentleman farmer and chemist

pH = pKa + log [HCO3-]

pCO2

Astrup and Severinghaus, The history of blood gasses, acids and bases. 1986

Van Slyke

US Clinical Chemist

1910 -1960s

“... the roles played…anions other than bicarbonate, and by

the cations, in determining the acid-base balance and the bicarbonate content of the blood.”

Peters and Van Slyke,

Quantitative Clinical Chemistry 1935

Bicarbonate and carbon dioxide

Henderson and Hasselbalch (before 1920) knew challenge:

To assess effects of disease on bicarbonate,

must account for effects on carbon dioxide:

Isolate non-respiratory effects

The rise of bicarbonateThe Modern Way in 1950s

Calculate bicarbonate using Henderson-Hasselbalch equation: Measure pH, pCO2 + know constants

pH = pKa + log [HCO3-]

pCO2

Carbonic acid true Bronstead-Lowry acid

Describe plasma pH ([H+]) with two measurable variables

Simple maths (B.C. - before calculators)

CO2 and bicarbonate = meaning of life, the universe, and everything

Christensen, Am J Med 1957

Intensive Care born 1952

Bicarbonate and carbon dioxide (again)

Siggaard-Andersen, Denmark, 1960s onward

Base Excess = amount of acid (mmol/l) added to return blood to pH 7.40 after equilibration

with pCO2 of 40 mmHg at 37oC

Quantify change in non-respiratory componentwww.osa.suite.dk

But…Schwarz and Relman, NEJM 1963

Boston Physicians

Found flaws in (original) base-excess: ABE

CO2 and bicarb “rules-of-thumb”

and “The Great Trans-Atlantic Acid-Base Debate”

Bunker, Anesthesiology, 1965

Then we have…

Siggaard-Andersen (fights back)

-Altered the “buffering” component “Standard base-excess”

-Gained support form Severinghaus (US)

Severinghaus, Am J Respir Crit Care Med, 1998

Peter Stewart 1921-1993Canadian physiologist working in USA

Stewart. Can J Physiol Pharmacol 1983

Acid base chemistry:“…piecemeal, qualitative, confusing…”

Returned to Arrhenius, Naunyn, Van Slyke QUANTITATIVEUsed principles of chemistry:

electroneutrality conservation of massdissociation of electrolytes

Strong ion acidosis- Stewart

Bicarbonate and hydrogen ions dependent factors

Bicarbonate is a marker not a mechanism

Base-excess is a marker

Sirker et al. Anaesthesia, 2002Miller’s Anesthesia

H+ / HCO3

CO2

SID

Weak acids

Kw + Ka

The Gamblegram

Gamble , 1950s

- chloride = acid- Gamblegram

- important aid to Stewart

Gamble,

Chemical Anatomy, Physiology

and Pathology of Extracellular Fluid 1954

Watson: www.ppn.med.sc.edu/watson/Acidbase/

Fencl

Boston based Physician

Originally suggested dividing base-excess into effects of:

• Sodium• Chloride• Albumin• Unmeasured ions

Gilfix J Crit Care 1993

FiggeBoston Physician-quantified the base-excess effect of albumin

Complex version Albumin effect (mmol/L) = (0.123pH- 0.631) X [42-albumin (g/l)].

Simple version:Albumin effect (meq/L) = 0.25 X (42-Albumin)

Figge, Crit Care Med 1998

Value for anion gap increasingly understood (even by Boston Physicians)

Fencl-Stewart = Figge-Fenclwww.acid-base.org

Kellum and the SIG

(NOT) Boston physician

Strong ion gap:

Sum of all measured strong ions,

and weak anions albumin, phosphate, bicarbonate

“anion-gap” on steroids

Kellum J Crit Care 1995

Net unmeasured ions

Lloyd, Crit Care Resus, 2005

Then I came along…

1. SBE = overall metabolic effect

2. Principal SID = Na – Cl (simplify Fencl), 140 – 102 = 38 (35)

3. Principal Weak acid = albumin (use simple Figge),

4. Rest = other ions

SBE = NaCl efffect + Albumin Effect + Other ion effect

For bedside use, not for the OCD

Not a Boston Physician

Simplify

In 2014 add lactate…

Plasma lactate now routinely measured

SBE =

NaCl Effect + Albumin Effect + Lactate Ion Effect + Other Ions

Lactate is a strong anion so effect on SBE = negative [lactate]

Median Reference Range = 1 mmol/L (ie when SBE = 0)

SBE effect = 1 – lactate, mmol/L

Eg Lactate ion effect of lactate of 4 mmol/L = - 3 mmol/L

Story, Anesthesia and Analgesia, 2006

SBE = NaCl + Albumin + Lactate + OI

78 yr old female with AAA post op

Na = 142, Cl = 110, Albumin = 26, Lactate = 6,

SBE = - 8 mmol/L

NaCl effect = 142 - 110 - 38 = - 6 mmol/l

Albumin effect = 0.25 x (42-26) = 0.25 x (16) = 4 mmol/l

Lactate effect = 1 - 6 mmol/L = -5 mmol/L

Other ions = SBE – NaCl effect – Albumin – Lactate

OI = -8 – (-6) - 4 – (-5)

= - 1 mmol/L

How will clinical acid-base evolve?

• Readily understood• Clinically useful• Quantifiable• Identifiable• Modifiable

Try different approaches in

YOUR clinical practice!

But, in my view…

Rules-of-thumb

The Neanderthals

Base-excess

The “sapiens”

way forward

But can the US cope?

…and add Stewart!

Thank you !!