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ACEP 2017DKA 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
Once 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
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
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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
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
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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
What should you immediately consider if glucose is falling but
bicarbonate values are not rising too?
Refractory Acidosis in DKA
• Dead Gut
• Abscess
• Sepsis
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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
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
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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
• 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:
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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
• 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
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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
HHS
• Volume resuscitate NSS like DKA
• Then 250-500 cc/hr
• KCI 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
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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
NSS, not insulin to start
DKA10 “Pearls”
Bolus then infuse NSS
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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