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SEMPA 2019Dangerous Acidosis

Corey M. Slovis, M.D.Vanderbilt University Medical Center

Metro Nashville Fire DepartmentNashville International Airport

Nashville, TN

All of these patients are acidotic …

What is the diagnosis?

Name That Acidosis

• Blindness

• Urine Findings

• Abdominal Pain

• Funny Breath

• Hypoglycemia

• Status Seizures

Name That Acidosis

• Hypoxia

• Hypocalcemia

• Papilledema

• “In a snow storm”

• pH < 6.8

• IV lorazepam

• Carbon monoxide

Name That Acidosis

Acidotic Diabetic “not in DKA” with relatively WNL

Blood Glucose

Metabolic Acidosis

HCO3 pH

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pH

pCO2

Respiratory Alkalosis

Experts in Acid-base can tell if there is Compensation vs. a

Second Primary Process

Compensation is Always the Opposite

Acidosis Alkalosis

Metabolic Respiratory

HCO3 pCO2

pH

pH

Respiratory Compensation inMetabolic Acidosis

Anion Gap

• The gap is the Positives minus the Negatives

• The gap is Na+- [Cl- + HCO3-]

• The gap should be about 8-12 (± 2)

• The gap should always be less than 15

Anion Gap

• WNL Gap but HCO3 = HARDUP

• An elevated gap = MUDPILES

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Elevated Anion Gap(Na+-[Cl- + HCO3

-] 15)

M Methanol

U UremiaD DKA, AKA

P Phenformin/Metaformin, Paracetamol, Propylene Glycol

I INH and Iron

L Lactic Acidosis

E Ethylene Glycol

S Salicylates, Solvents

K , Starvation Ketoacidosis

Normal Gap Acidosis(Low Bicarb but A.G. is NOT Elevated)

Hyperventilation (compensation)

Acids, Addison’s, Carbonic Anhydrase

R RTA

D Diarrhea

Ureteral Diversion, Ureterosigmoidostomy

P Pancreatic Fistula, Pancreatic Drainage

H

A

U

Inhibitors

Always check the Anion Gap

Even if the BMP looks normal!!

Elevated Anion Gaps

•Never secondary

•Never benign

•Never chronic

•Always potentially lethal

•Can never be ignored

Beware Acidotic Diabetes

• Are they compensated or is PCO2 telling you there is a Respiratory Acidosis or Primary Respiration Alkalosis

• Is it “Euglycemic” DKA

• Is it a big lactic acidosis due to …

How Sick in DKA?

• Mental Status

• BP/Pulse

• Respiratory Rate

• Finger Stick Glucose

• Serum pH

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Venous pH

VpH = 0.01 – 0.03 of Art pHCan an adult patient have

“euglycemic DKA”?

SGLT2 InhibitorsSodium Glucose Cotransporter 2 Inhibitors

• The Good- Inhibits proximal tubular reabsorption of glucose- May decrease the rate of diabetic kidney disease

• The Bad- Increases reabsorption of ketones

- Increases glucagon levels

- Thus promoting hepatic ketogenesis

J Clin Endocrinol Metab 2015;100:2849-52

Case Rep Crit Care 2016:ID 1656182 J Diab and Comp 2017;31:611-14

• SGLT-2 may cause Euglycemic DKA

• Glucose values 200-300

• Yet severe acidosis

• May take longer to clear keto acids

• Be wary, use PE, VS & pH, not just glucose

SGLT2 Inhibitors

• Invokana

• Farxiga

• Jardiance

• Glyxambi

• Synjardy

• Xigdou XR

• Canagliflozin

• Dapagliflozin

• Empagliflozin

• Empagliflozin/linagliptin

• Empagliflozin/metformin

• Dapagliflozin/metformin

• Canagliflozin

• Dapagliflozin

• Empagliflozin

• Empagliflozin/linagliptin

• Empagliflozin/metformin

• Dapagliflozin/metformin

Big Time Lactic Acidosis in DKA

• Sepsis

• Dead gut

OR

• Metformin induced lactic acidosis

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• Rare but serious

• Seen in ODs

• Also: acute decline in renal function*

• Lots of Bicarb acutely

• Dialysis with bicarbonate dialysate*beware GRF < 30

JAMA IntMed;2018;178:903-10 An alcoholic comes in with altered mental status and very ill appearing.

Someone says he was drinking “windex for car windshields”.

Is this methanol?

Toxic Alcohols

• Ethanol Acetaldehyde

• Isopropyl Acetone

• Methanol Formic Acid

• Ethylene Glycol Oxalic Acid

The most common errors in alcoholics are made by doctors

and nurses who assume

"He's just drunk."

Ann Emerg Med 1991;20:1146-1147

Ten Commandments of Emergency Medicine

• Assume the Worst

• Always err in a way the patient will suffer the least

Ann Emerg Med 1991;20:1146-1147

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Methanol

• CH3-OH; MW 32; 3.2 mg% of methanol = 1 mosm

• Formic acid and formaldehyde once metabolized

• Methanol is non-toxic; breakdown products are not

• Diagnosis: Profound acidosis, blindness, retinal edema, pancreatitis

Ethylene Glycol

HO-CH2-CH2-OH MW 62 each 6.2 mg% = 1 mosm

• Becomes oxalic acid once metabolized

• An antifreeze agent

• A sweetener for wine

• 40 - 60 deaths a year in USA

• Has no odor

• Profound acidosis from oxalic acid

• Renal failure from oxalate crystals in kidney

Isopropyl Alcohol

CH3-CHOH-CH3 MW 60 each 6.0 mg = 1 mosm

• Becomes acetone once metabolized

• Usually benign

• Twice as drunk, twice as sick, twice as long

• Ketosis without acidosis

• No anion gap

• Hemorrhagic gastritis, hypotension

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1) Get levels if available

2) Check osmolar gap

3) Treat based on history and/or physical and/or lab NOT just levels and/or gap

If they have already metabolized the toxin, they can be acidotic with low or no detectable

serum levels or osmolar gap!

To check for Methanol and Ethylene Glycol:

• Reverse Acidosis– 1 amp of bicarbonate for each 0.1 pH unit below 7.35

– 1 meq/kg over 5-10 min will raise pH by 0.1-0.15

– Get pH to 7.35-7.40

• Block Metabolism– Block Alcohol Dehydrogenas

– Begin Fomepizole (4-MP) • 15 mg/kg IV then 10 mg/kg IV Q 12 H

– Block Creation of Formic or Oxalic Acid

Treatment of Methanol and Ethylene Glycol

Is Bicarbonate Indicated in Wide Gap Metabolic

Acidosis?

Bicarbonate: Yes and No

Yes: in bicarbonate consuming overdoses like ASA, Methanol, Ethylene GlycolReplenish the consumed bicarbonate

No: for diseases that cause acidosis like DKA, Sepsis and Lactic Acidosis

Correct the underlying disease

Using Bicarbonate

Each amp raises pH by 0.1 if given in under 3-5 minutes

1 meq/kg raises pH by 0.1 – 0.15

Should you use bicarbonate in DKA?

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Bicarbonate UsePotential Benefits

Reverses Acidosis

Improves Cardiac Output

Increases Fibrillatory Threshold

Improves Insulin Sensitivity

Decreased Work of Breathing

Decreased Length of Coma

Potential Risks

Intracellular Acidosis

Increased Ca, H+, K fluxes

Hypokalemia, Tissue Hypoxia

Hyperosmolarity, Hypernatremia

Increased CO2 Generation,

Respiratory Acidosis

Paradoxical CSF Acidosis

• pH below 6.9 probably requires bicarbonate

• pH above 6.9 requires NO bicarbonate

Recommendations on Bicarbonate

It is generally agreed that:

• Be “forced” into using bicarbonate

NEJM 2001;344:264-269

The only therapeutic variable associated with cerebral edema in children with DKA was

the administration of Bicarbonate

• Low pH, low pCO2 levels and amount of dehydration also important determinants

Rapid IV administration of bicarbonate in DKA can cause a respiratory acidosis in the brain

Rule 1: CO2 freely Crosses BBB

CO2

CO2

CO2 CO2

Rule 2: HCO3 does not cross BBB

HCO3

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Rule 3: Hyperventilation is based on venous pH not

CSF pH

HCO3 CO2 + H2OH2CO3

Bicarbonate is in equilibrium with C02

HCO3 CO2H2CO3

Giving HCO3 raises CO2

• pCO2 crosses freely

• HCO3 doesn’t cross

• Ventilation rate (pCO2) determined

BBB “Rules”

by venous pH

• Serum HCO3 will rise

• Thus serum pH will rise

• If pH rises, less hyperventilation

• Serum pCO2 will rise on venous side

• Causing pCO2 to rise on CSF side too

If you give HCO3 rapidly IV:

HCO3 CO2 + H2OH2CO3

Bicarbonate is in equilibrium with C02

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Giving IV Bicarbonate

can cause CNS

Hypercarbia

Push Bicarb in DKA ONLY For

• Hyperkalemic emergency

• Impending cardiopulmonary arrest

Children are at Real Risk for Cerebral Edema.

Be Careful!

140 100

3.8 10

BUN = 20

GLU = 70

pH = 7.32

pCO2 = 20

pO2 = 80

What is the differential of AMS?

Immediate Rule Out?

A 23 yo man presents with altered mental status. He is agitated, febrile and hyperventilating.

(V pH 7.30)

AMSStatus Seizures

• Vital Signs

• Toxic–Metabolic

• Structural

• Infectious

• Epilepsy

• Vital Signs

• Toxic–Metabolic

• Structural

• Infectious

• Psychiatric

Whenever you have a WGMA and a 1 Respiratory Alkalosis always

immediately consider and rule out:

ASPIRIN

SEPSIS

o

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X 100,100

140 100

4.0 15

pH = 7.30

pCO2 = 30

pO2 = 98

O2 sat = 100%

A 19 yo Jeet Kun Do Sensei is found down in his dojo.

140 100

4.0 15

pH = 7.30

pCO2 = 30

pO2 = 98

O2 sat = 100%

Any new Rule of 5 to use here?

PE Decorticate, Papilledema

ECG Diffuse ST and T waves changes

pH = 7.30

pCO2 = 30

pO2 = 98

O2 Sat = 100%

Trust No OneBelieve Nothing

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67J Respir Dis 2001;22:289-296 68

Co-Oximetry

• Measures true saturation's

• Measures at 4 wavelengths

• Specifically evaluates

–Saturated Hgb (O2)

–Desaturated Hgb (CO2)

–Carbon Monoxide (CO)

–Methemoglobin (Me)

69J Respir Dis 2008;29:74-82

AMS of Unknown Cause5 ABG Values

• pO2

• pCO2

• pH

• Measured O2 Sat

• CO Level

SummaryTest

Name That Acidosis• Methanol

• Ethylene Glycol, DKA, RF

• Methanol, Iron, DKA, Sepsis, ASA

• Uremia, DKA, Aspirin (Methyl Salycilate)

• ASA, Sepsis, Methanol, E.G.

• INH, Lactic Acidosis

• Blindness

• Urine Findings

• Abdominal Pain

• Funny Breath

• Hypoglycemia

• Status Seizures

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Name That Acidosis

• Hypoxia

• Hypocalcemia

• Papilledema

• “In a snow storm”

• pH < 6.8

• IV lorazepam

• Carbon monoxide

• Lactic Acidosis

• Ethylene Glycol

• Methanol

• Methanol

• INH, ME, EG

• Propylene glycol

• Lactic acidosis

Name That Acidosis

Acidotic Diabetics “not in DKA” with relatively WNL

Blood Glucose

SGLT2 Inhibitors

• AMS, toxic delirium

• Febrile and thrashing

• Seizing

• DIC/MOSF

• Hypoglycemic, Hypokalemic

Aspirin

Status Seizures

refractory to anti-seizure medications

INH

Papilledema vs Renal Failure

vs Ketotic but not acidotic

Methanol vs EG vs Isopropyl

Severe acidosis that disappears with D5NSS

AKA

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Gold or silver faces and a WGMA

Solvents

Anxious, healthy and WNL gap acidosis

Hyperventilation

SUMMARY

Elevated Anion Gap(Na+-[Cl- + HCO3

-] 15)

M Methanol

U UremiaD DKA, AKA

P Phenformin/Metaformin, Paracetamol, Propylene Glycol

I INH and Iron

L Lactic Acidosis

E Ethylene Glycol

S Salicylates, Solvents

K , Starvation Ketoacidosis

Whenever you have a WGMA and a 1 Respiratory Alkalosis always

immediately consider and rule out:

ASPIRIN

SEPSIS

o

Big Time Lactic Acidosis in DKA

• Sepsis

• Dead gut

OR

• Metformin induced lactic acidosis

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Using Bicarbonate

Each amp raises pH by 0.1 if given in under 3-5 minutes

1 meq/kg raises pH by 0.1 – 0.15

Always check the Anion Gap

Even if the BMP looks normal!!