4/16/2019

SEMPA 2019 Dangerous Acidosis All of these patients are acidotic … Corey M. Slovis, M.D. Vanderbilt University Medical Center What is the diagnosis? Metro Nashville Fire Department Nashville International Airport Nashville, TN

Name That Acidosis Name That Acidosis

• Blindness • Hypoxia • Urine Findings • Hypocalcemia • Papilledema • Abdominal Pain • “In a snow storm” • Funny Breath • pH < 6.8 • Hypoglycemia • IV lorazepam • Carbon monoxide • Status Seizures

Name That Acidosis Metabolic Acidosis

Acidotic Diabetic “not in HCO3 pH DKA” with relatively WNL Blood Glucose

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Respiratory Alkalosis

pCO2 Experts in Acid-base can tell if there is Compensation vs. a Second Primary Process

pH

Compensation is Respiratory Compensation in Metabolic Acidosis Always the Opposite HCO pH 3 pCO2 Acidosis Alkalosis

Metabolic Respiratory

pH

Anion Gap Anion Gap

• The gap is the Positives minus the Negatives • An elevated gap = MUDPILES + - - • The gap is Na -[Cl + HCO3 ]

• WNL Gap but HCO3  = HARDUP • The gap should be about 8-12 (± 2)

• The gap should always be less than 15

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Elevated Anion Gap Normal Gap Acidosis + - - (Na -[Cl + HCO3 ]  15) (Low Bicarb but A.G. is NOT Elevated)

M Methanol H Hyperventilation (compensation) U Uremia A Acids, Addison’s, Carbonic Anhydrase DK DKA, AKA, Starvation Ketoacidosis Inhibitors P Phenformin/Metaformin, Paracetamol, Propylene Glycol RRTA I INH and Iron D Diarrhea L Lactic Acidosis U Ureteral Diversion, Ureterosigmoidostomy E Ethylene Glycol P Pancreatic Fistula, Pancreatic Drainage S Salicylates, Solvents

Elevated Anion Gaps •Never secondary

Always check the Anion Gap •Never benign Even if the BMP looks normal!! •Never chronic

•Always potentially lethal

•Can never be ignored

Beware Acidotic Diabetes How Sick in DKA?

• Are they compensated or is PCO2 telling • Mental Status you there is a Respiratory Acidosis or Primary Respiration Alkalosis • BP/Pulse

• Is it “Euglycemic” DKA • Respiratory Rate • Finger Stick Glucose • Is it a big lactic acidosis due to … •Serum pH

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Venous pH

Can an adult patient have VpH = 0.01 – 0.03 of Art pH “euglycemic DKA”?

SGLT2 Inhibitors Sodium Glucose Cotransporter 2 Inhibitors J Clin Endocrinol Metab 2015;100:2849-52 • The Good Case Rep Crit Care 2016:ID 1656182 J Diab and Comp 2017;31:611-14 - Inhibits proximal tubular reabsorption of glucose • SGLT-2 may cause Euglycemic DKA - May decrease the rate of diabetic kidney disease • Glucose values 200-300 • The Bad • Yet severe acidosis - Increases reabsorption of ketones - Increases glucagon levels • May take longer to clear keto acids - Thus promoting hepatic ketogenesis • Be wary, use PE, VS & pH, not just glucose

SGLT2 Inhibitors Big Time Lactic Acidosis in DKA • Invokana • Canagliflozin •Sepsis • Farxiga • Dapagliflozin • Dead gut • Jardiance • Empagliflozin • Glyxambi • Empagliflozin/linagliptin OR • Synjardy • Empagliflozin/metformin • Metformin induced lactic acidosis • Xigdou XR • Dapagliflozin/metformin

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JAMA IntMed;2018;178:903-10 An alcoholic comes in with altered • Rare but serious mental status and very ill appearing. • Seen in ODs Someone says he was drinking • Also: acute decline in renal function* “windex for car windshields”. • Lots of Bicarb acutely Is this methanol? • Dialysis with bicarbonate dialysate *beware GRF < 30

Toxic Alcohols

• Ethanol  Acetaldehyde The most common errors in alcoholics are made by doctors • Isopropyl  Acetone and nurses who assume • Methanol  Formic Acid "He's just drunk."

• Ethylene Glycol  Oxalic Acid

Ten Commandments of Emergency Medicine

Ann Emerg Med 1991;20:1146-1147

• 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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To check for Methanol Treatment of Methanol and and Ethylene Glycol: Ethylene Glycol

1) Get levels if available • Reverse Acidosis – 1 amp of bicarbonate for each 0.1 pH unit below 7.35 2) Check osmolar gap – 1 meq/kg over 5-10 min will raise pH by 0.1-0.15 – Get pH to 7.35-7.40 3) Treat based on history and/or physical and/or lab NOT just levels and/or gap • Block Metabolism – Block Alcohol Dehydrogenas If they have already metabolized the toxin, – Begin Fomepizole (4-MP) they can be acidotic with low or no detectable • 15 mg/kg IV then 10 mg/kg IV Q 12 H serum levels or osmolar gap! – Block Creation of Formic or Oxalic Acid

Bicarbonate: Yes and No

Is Bicarbonate Indicated Yes: in bicarbonate consuming overdoses like ASA, Methanol, Ethylene Glycol in Wide Gap Metabolic Replenish the consumed bicarbonate Acidosis? 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 Should you use bicarbonate in DKA?

1 meq/kg raises pH by 0.1 – 0.15

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Bicarbonate Use Recommendations on Potential Benefits Potential Risks Bicarbonate Reverses Acidosis Intracellular Acidosis It is generally agreed that:

Improves Cardiac Output Increased Ca, H+, K fluxes • pH above 6.9 requires NO bicarbonate Increases Fibrillatory Threshold Hypokalemia, Tissue Hypoxia

Improves Insulin Sensitivity Hyperosmolarity, • pH below 6.9 probably requires Hypernatremia bicarbonate

Decreased Work of Breathing Increased CO2 Generation, Respiratory Acidosis • Be “forced” into using bicarbonate Decreased Length of Coma Paradoxical CSF Acidosis

NEJM 2001;344:264-269

The only therapeutic variable associated with Rapid IV administration of cerebral edema in children with DKA was bicarbonate in DKA can cause a the administration of Bicarbonate respiratory acidosis in the brain

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

Rule 1: CO freely Crosses BBB 2 Rule 2: HCO3 does not cross BBB

CO2 HCO3

CO2

CO2 CO2

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Bicarbonate is in equilibrium with C02

Rule 3: Hyperventilation is based on venous pH not HCO3 H2CO3 CO2 + H2O CSF pH

BBB “Rules”

Giving HCO3 raises CO2

•pCO2 crosses freely

HCO3 H2CO3 CO2 •HCO3 doesn’t cross

• Ventilation rate (pCO2) determined by venous pH

If you give HCO3 rapidly IV: Bicarbonate is in equilibrium with C02 •Serum HCO3 will rise • Thus serum pH will rise HCO3 H2CO3 CO2 + H2O • If pH rises, less hyperventilation

•Serum pCO2 will rise on venous side

• Causing pCO2 to rise on CSF side too

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Push Bicarb in DKA ONLY For

Giving IV Bicarbonate • Hyperkalemic emergency can cause CNS Hypercarbia • Impending cardiopulmonary arrest

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

Children are at Real Risk 140 100 BUN = 20 pH = 7.32 3.8 for Cerebral Edema. 10 GLU = 70 pCO2 = 20

pO2 = 80 Be Careful! . What is the differential of AMS? . Immediate Rule Out?

(V pH 7.30)

Status Seizures AMS Whenever you have a WGMA and a 1o Respiratory Alkalosis always • Vital Signs • Vital Signs immediately consider and rule out: • Toxic–Metabolic • Toxic–Metabolic • Structural • Structural ASPIRIN • Infectious • Infectious SEPSIS • Epilepsy • Psychiatric

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X 100,100

pH = 7.30 pH = 7.30 140 100 140 100 pCO2 = 30 pCO2 = 30 4.0 15 4.0 15 pO2 = 98 pO2 = 98

O2 sat = 100% O2 sat = 100% PE Decorticate, Papilledema

. A 19 yo Jeet Kun Do Sensei is found ECG Diffuse ST and T waves changes down in his dojo. . Any new Rule of 5 to use here?

pH = 7.30

pCO2 = 30

pO2 = 98

O2 Sat = 100% Trust No One Believe Nothing

11 4/16/2019

Co-Oximetry

• Measures true saturation's • Measures at 4 wavelengths • Specifically evaluates –Saturated Hgb (O2) –Desaturated Hgb (CO2) –Carbon Monoxide (CO) –Methemoglobin (Me) J Respir Dis 2001;22:289-29667 68

AMS of Unknown Cause 5 ABG Values

•pO2

•pCO2 •pH

• Measured O2 Sat •CO Level

J Respir69 Dis 2008;29:74-82

Name That Acidosis • Blindness • Methanol

• Urine Findings • Ethylene Glycol, DKA, RF

Summary • Abdominal Pain • Methanol, Iron, DKA, Sepsis, ASA

Test • Funny Breath • Uremia, DKA, Aspirin (Methyl Salycilate)

• Hypoglycemia • ASA, Sepsis, Methanol, E.G.

• Status Seizures • INH, Lactic Acidosis

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Name That Acidosis Name That Acidosis

• Hypoxia • Lactic Acidosis

• Hypocalcemia • Ethylene Glycol

• Papilledema • Methanol Acidotic Diabetics “not in DKA” with relatively WNL • “In a snow storm” • Methanol Blood Glucose • pH < 6.8 • INH, ME, EG

• IV lorazepam • Propylene glycol SGLT2 Inhibitors

• Carbon monoxide • Lactic acidosis

• AMS, toxic delirium • Febrile and thrashing Status Seizures • Seizing refractory to anti-seizure medications • DIC/MOSF INH • Hypoglycemic, Hypokalemic Aspirin

Papilledema vs Renal Failure Severe acidosis that disappears with D NSS vs Ketotic but not acidotic 5 AKA Methanol vs EG vs Isopropyl

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Gold or silver faces and a WGMA Anxious, healthy and WNL gap acidosis Solvents Hyperventilation

Elevated Anion Gap + - - (Na -[Cl + HCO3 ]  15) M Methanol U Uremia DK DKA, AKA, Starvation Ketoacidosis SUMMARY P Phenformin/Metaformin, Paracetamol, Propylene Glycol I INH and Iron L Lactic Acidosis E Ethylene Glycol S Salicylates, Solvents

Big Time Lactic Acidosis in DKA

Whenever you have a WGMA and a •Sepsis 1o Respiratory Alkalosis always immediately consider and rule out: • Dead gut

ASPIRIN OR

SEPSIS • Metformin induced lactic acidosis

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Using Bicarbonate

Each amp raises pH by 0.1 if given in under 3-5 minutes Always check the Anion Gap Even if the BMP looks normal!!

1 meq/kg raises pH by 0.1 – 0.15

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