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ACEP 2018DKA and Hyperosmolar

SyndromePearls and Pitfalls

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

Metro Nashville Fire DepartmentNashville International Airport

Nashville, TN

DKA

A 21 year old grad student

Presents in DKA.

How many causes of

DKA are there?

Mastering Emergency Medicine

• Secure the ABC’s

• Consider or give NGT

• Five Causes

•Five Steps

• Five Reasons for almost everything

5 Causes of DKA

• Infection

• Infarction

• Infant

• Indiscretion

• Insulin lack

DKA – Insulin Lack5 Actions of Insulin

• Drives Glucose into cell

• Drives K into cell

• Anabolic

• Blocks Fat breakdown

• Blocks protein breakdown

→ Glu ↑

→ K ↑

→ Catabolic

→ FFA Acids ↑

→ Keto Acids ↑

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Diabetes Care 2009;32:1335-1343

• Current State of the Art

• Standard of Care

• Consensus Statement of ADA

Med Clin N Am 2017;101:587-606Metabolism 2016;65:507-21

Although DKA is much more common in Type 1 DM, 1/3 of DKA cases occur in patients classified as

Type 2 DM (“Adult onset”)

J Clin Endocrinol Metab 2015;100:2849-52

Mild Moderate Severe

pH 7.25 – 7.30 7.00 – 7.24 below 7.0

HCO3 15 - 18 10 - 15 below 10

MS Alert Alert +Stupor or

Coma

Three Levels of DKA

How Sick in DKA?

• Mental Status

• BP/Pulse

• Respiratory Rate

• Finger Stick Glucose

• Serum pH

Can an adult patient have “euglycemic DKA”?

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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

Do you need an ABG in DKA?

Acad Emerg Med 2003;10:836-841

• 200 ABGs and VpHs in DKA Patients

• ABG pO2 and pCO2 changed Rx in 2/200

• Very high Art pH/V pH correlation (0.95)

Routinely Use VpH in DKA

Venous pH

Very high Art pH/V pH correlation (0.95)

How many therapies should you consider in DKA?

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Five Therapies to Consider in DKA

v

• Volume

• Insulin

• Potassium

• Bicarbonate

• Phosphate

......................

Therapy and Rationales in DKA

• Volume

• Insulin

• Potassium

– Enough to re-hydrate

– But don’t wash out ketones

– Saturate receptors

– And keep saturated

– Avoid hyperkalemia early

– But avoid hypokalemia later

• Bicarbonate

• Phosphate

– Rarely needed

– Use for decompensation

– Only cachectic adult patients– Common in children

– Use for values below 1.0 – 1.5

Therapy and Rationales in DKA - 2

How dehydrated are DKA patients?

VOLUME in DKA

• 3 - 5 liters is usual deficit in mild-moderate DKA

• 5 - 6 liters is usual fluid deficit in severe DKA

Deficits: Is aggressive fluid management optimal

in adults?

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JAMA 1989;262:2108-13

Don’t “wash out” all the Keto Acids ….

Let the Patient Metabolize Them

Volume Therapy in DKA

• NSS at 500 cc/hr x 4 hours

• Switch to NSS at 250 cc/hour

Stable Patients:

Profound Dehydration:• NSS wide open until well perfused

• Bolus healthy patients with at least 1,000 cc of NSS (20 cc/kg) rapidly

Begin Therapy:

For mild DKA you can just

begin therapy at 250cc/hr

with smaller or no bolus

Should you ever use half

normal saline in treating DKA?

NSS vs. ½ NS

• NSS is the “standard”

• Use initially to volume load

• Consider ½ NS if corrected serum

sodium is elevated above normal

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The easiest way to correct for Na in DKA is

2 meq ↓ Na for every 100mg/dl glucose

“Real Formula” –1.6 ↓ Na/100 mg/dl glucose to 4002.4 ↓ Na/100 mg/dl > 400

134 96

5.0 10

Glu = 750

Corrected Na = 134 + 2/100 glu ↑

Corrected Na = above 140 (145-148)

Use ½ NS in this patient

What is better fluid in DKANormal saline (NSS) or Lactated Ringer’s (LR)?

• 57 pts randomized to NSS vs LR

• pH 6.9-7.2, average glucose 470

• Double-blind, randomized

• Evaluated time to pH 7.32 and glucose < 250

Q J Med 2012;105:337-43

0

100

200

300

400

500

600

700

Resolution of DKA: pH and Glucose NSS vs LR

Q J Med 2012;105:337-43

pH to 7.32 Glucose to 250

683

P=0.251 P=0.014300

410

540

NSS NSSLR LR

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LR vs NSS in DKATake Homes

• A small study that does show bicarbonate rises sooner but glucose falls slower with LR

• No proven benefit of modifying current American Diabetes Association recommendations for treatment of DKA

N Engl J Med 2018;378:829-39

Is LR or NSS more advantageous in ED patients admitted to the ICU?

• 15,802 adult pts from 1 hospital

• Pragmatic, multiple cross overs

• ED pts who were then ICU admitted

• 1,000 ml LR/Plasma-Lyte vs 1,020 ml NSS (median)

• Compared mortality, new RRT, persistent Cr 2 x

N Engl J Med 2018;378:829-39 N Engl J Med 2018;378:829-39

0%

1%

2%

3%

4%

5%

6%

7%

8%

9%

10%

11%

12%

Hu

nd

red

s

11.1%

10.3%

Death, Renal Replacement Therapy and Cr 2 x

Mortality

2.9% 2.5%

N Engl J Med 2018;378:829-39

NSS NSSLR LR

6.6%6.4%

Cr

NSS LR

RRT

p < 0.6

p < 0.08

p < 0.06 • 49,737 pts ages 0-17, retrospective study

• Pediatric Health Information System Database

• 43,841 NSS vs 1,762 (4%) LR

• Most DKA “mild to moderate”

• Evaluated LOS and incidence of cerebral edema

Ped Emerg Care 2018 Aug;ePub ahead of print

Is LR superior to NSS in Pediatric DKA?

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0%

1%

2%

3%

4%

5%

0.8%

Cerebral Edema

LR

3.6%

NSS

Ped Emerg Care 2018 Aug;ePub ahead of print

Study shows more than a 4x increase incidence of cerebral edema with NSS

vs LR (3.6% vs 0.8%)

Ped Emerg Care 2018 Aug;ePub ahead of print

However 5.9% of NSS had “severe” or “extreme” DKA vs only 1.6% treated

with LR or about 4x as many seriously ill patients at risk for cerebral edema

Not clear…

ADA recommends NSSbut it’s from 2009

My bias is LR

What Fluid Should You Use In DKAOnce Serum Glucose approaches 250 mg%:

Switch to Glucose containing fluids

(D51/2 NS at 150 - 250 cc/hr)

Insulin

• Provide a loading dose, and then

• Keep all receptor sites saturated

Current recommendation:

Each unit of insulin moves about 4-5 grams of glucose into cell

Insulin Dosing

• Loading Dose

• Maintenance Dose

– 0.1 units/kg IV Push

– 0.1 units/kg per hour

In general load adults, not children

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J Emerg Med 2010;38:422-427

• ADA recommends insulin loading in adults

• Loading dose saturates receptors

• Loading may cause hypoglycemia in children

• Loading not recommended in Peds DKA

• Hypoglycemia seen in adults too!

J Emerg Med 2010;38:422-427

• IV insulin bolus not of proven benefit

Conclusions

• May cause more hypoglycemia

Can you use SQ insulin in DKA? • 5 small studies, mild-moderate DKA

• All show SQ is similar to IV

• But requires SQ injections Q 1-2 h

• Close following of blood glucose

• Never in severe acidosis, hypotension, AMS

J Emerg Med 2015;48:530-8

What do you need to know about SQ insulin treatment of DKA?

SQ Insulin in DKATake Homes

• SQ can avoid ICU admission

• But floor RNs often can’t do

• Still requires close monitoring

• Yes for a step down unit

• Not for sick patients

Potassium in DKA

• The average K deficit in DKA is 3 - 5 meq/kg IBW

• The ECG does not accurately predict hypokalemia

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Potassium Dosing in DKA

In general

But …

10 meq/hr

KCL Replacement in First Hours of DKA

Hyperkalemia (above 5.3) Hold K for 1 hr, recheck K

“DKA Kalemia” (4.0 - 5.3) KCL 10 meq/hr

Hypokalemia (3.5 - 4.0) KCL 20 meq/hr

Severe HypoK (below 3.5) Hold InsulinKCL 20 - 60 meq/hr/constant ECG

Unexpected Death in DKA

• First hour or two when sick:

• Later while “stabilizing”:

– Hyperkalemia

– Hypokalemia

Should you begin insulin along with the IV fluids?

NO!!

Glucose + insulin drives K into the cell

Hypokalemia + DKA + insulin = VF, VT or Toursades

Always determine the serum potassium before starting insulin

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What should you immediately consider if glucose is falling but

bicarbonate values are not rising too?

Refractory Acidosis in DKA

• Dead Gut

• Abscess

• Sepsis

Should you use bicarbonate in DKA?

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

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

BBBRule 1: CO2 freely Crosses BBB

CO2

CO2

CO2 CO2

Rule 2: HCO3 does not cross BBB

HCO3 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

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• 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:

Push Bicarb ONLY For:

• Hyperkalemic emergency

• Impending cardiopulmonary arrest

Children are at Real Risk for Cerebral Edema.

Be Careful!

Phosphate Therapy in DKA

• No proven benefit

• Rarely used in adults

• Up to ½ of K requirements given as

• Check with your pediatrician

K2 PO4 in pediatric patients

HyperosmolarHyperglycemia

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• Not enough insulin to move glucose

• Enough insulin to drive K into cell

• Enough insulin to block catabolic state

• Enough to not breakdown fat & protein

• Extreme glucose elevations

Hyperosmolar Hyperglycemic State (HHS)

(HONK, NKHC, HHNK)

Hyperosmolar Hyperglycemic State (HHS)

(HONK, NKHC, HHNK)

• Glucose > 600

• pH > 7.30

• HCO3 > 18

• Osm > 350

A disease usually of the elderlyA mortality of up to 20%Profound dehydration

HHS

• AMS in most patients

• Up to 50% present in coma

• Seizures in up to 1/4 of patients

• Often focal (20 - 85% of reported cases)

• Patients usually lethargic or comatose

• 10% present without AMS

Hyperosmolar Hyperglycemic State (HHS)

(HONK, NKHC, HHNK)DKA

Insulin levels very lowKetoacidosis profoundGlucose 600HCO3 5 - 15OSM 300 - 325Age youngOnset acuteAssociated diseases rareSeizures very rareComa rareMortality approaches 0

HHSmay be normalminimal1,000+20 – 24350+oldchroniccommoncommoncommon10 – 20%

When you see HHS think:

• Precipitating cause- Pneumonia- UTI

• Beware- AMI- CVA- Sepsis

• It takes hours to 1-2 days to develop DKA

–Treat aggressively

• It takes many days to weeks to develop NKHC

– Do not treat aggressively

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HHS

• Volume resuscitate like DKA

• Then 250-500 cc/hr

• KCL at about 10meq/hr

• Be careful: older, risk of HF, fluid overload

• I go slow with fluids post bolus

Insulin in NKHC

• ADA guidelines recommend bolus and maintenance like in DKA

• 0.1 units/kg bolus and 0.1 units/kg per hour

• My bias, follow very, very closely

• I use less insulin until rate of glucose known

Summary

Therapy and Rationales in DKA

• Volume

• Insulin

• Potassium

– Enough to re-hydrate

– But don’t wash out ketones

– Saturate receptors

– And keep saturated

– Avoid hyperkalemia early

– But avoid hypokalemia later

• Bicarbonate

• Phosphate

– Rarely needed

– Use only for decompensation

– Only cachectic patients

– Use for values below 1.0 – 1.5

Therapy and Rationales in DKA - 2 HHS

• Find cause

• Treat carefully

• Mortality – much higher

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NSS or LR, not insulin to start

DKA10 “Pearls”

Bolus then infuse NSS or LR

Beware “WNL” sodium in DKA

Check K before starting insulin

VpH not ABG

Refractory acidosis: Dead gut, abscess, sepsis

DKA10 “Pearls”

SGLT-2: glucose WNL, pH

Bicarbonate is hyperosmolar and hypercarbic

K2PO4 only if PO4 below 1-1.5

Hyperosmolar Glu state = precipitating cause

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