(+)CoreyM.Slovis,MD,FACEP
Professor,EmergencyMedicineandMedicine;
Chairman,DepartmentofEmergencyMedicine,
VanderbiltUniversityMedicalCenter,Nashville,
Tennessee;MedicalDirector,MetroNashvilleFire
DepartmentandNashvilleInternationalAirport
AdvancedPracticeProvider
Academy
April14‐18
SanDiego,CA
DiabetesandBloodGlucoseEmergencies:How
SweetItIs!
Diabetesandderangementsofbloodglucosemetabolism
representsasignificantnumberoftrueemergenciesas
wellashasanimpactonavastnumberofpatientswho
presenttotheemergencydepartment.Hyperglycemicand
hypoglycemicstatesarenotonlylife‐threateningbutcan
mimicothercriticalpathologicconditionsandneedtobe
identifiedandmanagedquickly.Thiscoursewill
introduceapproachestotheidentificationand
managementofpatientswithbloodglucoseemergencies,
diabeticketoacidosis(DKA)andhyperglycemic
hyperosmolarsyndrome(HHS)—andthecontroversy
thatsurroundsthemanagementofthesediseases.The
extremeoppositeoftheaboveprocessesandthecauses
andmanagementofhypoglycemicstatesalsowillbe
discussed.
Objectives:
 Identifypatientswhohavebloodglucose
derangementsandreviewsomecommonconditions
thattheymimic.
 Describethecommonpresentation,laboratory
abnormalities,treatmentandadmissioncriteriafor
patientswithdiabeticemergencies.
 Discusscurrentdifferencesbetweentheapproachto
adultsandpediatricpatientswithhypoglycemia.
Date:4/14/2014
Time:2:45PM‐3:15PM
CourseNumber:MO‐12
(+)Nosignificantfinancialrelationshipstodisclose
DKA, HONK,
Hypoglycemia
DKA
Corey M. Slovis, M.D.
Vanderbilt University Medical Center
Metro Nashville Fire Department
Nashville International Airport
Nashville, TN
Mastering Emergency Medicine
A 21 year old grad student
Presents in DKA.
How many causes of
DKA are there?
5 Causes of DKA
• Secure the ABC’s
• Consider or give NGT
• Five Causes
• Five Steps
• Five Reasons for almost
everything
DKA – Insulin Lack
5 Actions of Insulin
• Infection
• Drive Glucose into cell
→ Glu ↑
• Infarction
• Drive K into cell
→K↑
• Infant
• Anabolic
→ Catabolic
• Indiscretion
• Block Fat breakdown
→ FFA Acids ↑
• Insulin lack
• Block protein breakdown → Keto Acids ↑
1
Diabetes Care 2009;32:1335-1343
How Sick in DKA?
• Mental Status
• BP/Pulse
• Current State of the Art
• Respiratory Rate
• Standard of Care
• Finger Stick Glucose
• Consensus Statement of ADA
• Venous pH
Three Levels of DKA
Mild
pH
pH in DKA
Moderate
7.25 – 7.30 7.00 – 7.24
Severe
below 7.0
HCO3
15 - 18
10 - 15
below 10
MS
Alert
Alert +
Stupor or
Coma
• Which is better, an ABG with
arterial pH or just a venous pH?
Acad Emerg Med 2003;10:8
Routinely Use VpH in DKA.
• 200 ABGs and VpHs in DKA Patients
• ABG pO2 and pCO2 changed Rx in 2/200
• Very high correlation between Art pH vs. V pH (0.95)
2
Five Therapies to Consider in DKA
How many therapies should
you consider in DKA?
• Volume
v• Insulin
• Potassium
......................
• Bicarbonate
• Phosphate
Therapy and Rationales in DKA
• Volume
– Enough to re-hydrate
– But don’t wash out ketones
• Insulin
– Saturate receptors
– And keep saturated
• Potassium
– Avoid hyperkalemia early
– But avoid hypokalemia later
Therapy and Rationales in DKA - 2
• Bicarbonate
– Rarely needed
– Use for decompensation
• Phosphate
– Only cachectic adult patients
– Common in children
– Use for values below 1.0 – 1.5
VOLUME in DKA
Deficits:
• 3 - 5 liters is usual deficit in
mild-moderate DKA
What is the best IV flow
rate in DKA for the first
3 to 4 hours?
• 5 - 6 liters is usual fluid deficit
in severe DKA
3
JAMA 1989;262:2108-13
Don’t “wash out” all the
Keto Acids ….
Let the Patient
Metabolize Them
Volume Therapy in DKA
Begin Therapy:
• Bolus healthy patients with at least
1,000 cc of NSS (20 cc/kg) rapidly
Stable Patients:
• NSS at 500 cc/hr x 4 hours
• Switch to NSS at 250 cc/hour
For Mild DKA You Can Just
Begin Therapy at 250cc/hr
with Smaller or no Bolus.
Profound Dehydration:
• NSS wide open until well perfused
NSS vs. ½ NS
• NSS is the “standard”
• Use initially to volume load
• Consider ½ NS if corrected serum
sodium is elevated
4
The easiest way to
correct for Na in DKA is
2-2.5 meq ↓ Na for every
100mg/dl ↑ glucose
“Real Formula” –
1.6 ↓ Na/100 ↑ mg/dl glucose to 400
4.0 ↓ Na/100 ↑ mg/dl > 400
Once Serum Glucose
approaches 250 mg%:
Switch to Glucose
containing fluids
(D51/2 NS at 150 - 250 cc/hr)
Cerebral Edema and DKA
• Seen in children
• Increased morbidity and mortality
• Leading cause of death in pediatric DKA
NEJM 2001;344:264-269
The only therapeutic variable associated with
cerebral edema in children with DKA was
the administration of Bicarbonate.
• Lower pH and pCO2 increases incidence
• Aggressive fluids also implicated
• Low pH, low pCO2 levels and amount of
dehydration also important
Fluids in DKA
• Bolus: adults routinely, children rarely
• Correct hypoperfusion ASAP
• Less, not more, once euvolemic
Children are at Real Risk
for Cerebral Edema.
Be Careful!
• Under-resuscitation is to be avoided
• Acidosis and Dehydration are your enemies
5
Insulin
Insulin Dosing
You must:
• Provide a loading dose, and then
• Keep all receptor sites saturated
Each unit of insulin moves about
4-5 grams of glucose into cell.
• Loading Dose
– 0.1 units/kg IV Push
• Maintenance Dose
– 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
J Emerg Med 2010;38:422-427
Conclusions
• IV insulin bolus not of proven benefit
• Loading may cause hypoglycemia in children
• Loading not recommended in Peds DKA
• May cause more hypoglycemia
Potassium in DKA
If glucose fall is not at
100 mg/dl per hour, rebolus, double
infusion rate and look again for infection,
infarction and infant.
• The average K deficit in DKA
is 3 - 5 meq/kg IBW
• The ECG does not accurately
predict hypokalemia
6
Potassium Dosing in DKA
A patient in DKA presents with
K=5.1, pH =7.0, good urine output.
How much KCl should be given in
the first 4 hours?
In general
10 meq/hr
But …
KCL Replacement in First
Hours of DKA
Be sure K is in the
DKA range of WNL.
4.0 - 5.3
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 Insulin
KCL 20 - 60 meq/hr/constant ECG
Unexpected Death in DKA
• First hour or two when sick:
– Hyperkalemia
• Later while “stabilizing”:
A patient is treated for DKA and his
glucose falls appropriately.
His bicarbonate however, does not rise.
First thoughts?
– Hypokalemia
7
Refractory Acidosis in DKA
• Dead Gut
• Sepsis
• Abscess
Recommendations on
Bicarbonate
Bicarbonate Use
Potential Benefits
Potential Risks
Reverses Acidosis
Intracellular Acidosis
Improves Cardiac Output
Increased Ca, H+, K fluxes
Increases Fibrillatory Threshold
Hypokalemia, Tissue Hypoxia
Improves Insulin Sensitivity
Hyperosmolarity,
Hypernatremia
Decreased Work of Breathing
Increased CO2 Generation,
Respiratory Acidosis
Decreased Length of Coma
Paradoxical CSF Acidosis
HCO3
PCO2
pH
24
40
7.40
20
35
7.35
15
30
7.30
• pH between 6.9 - 7.0 may require
bicarbonate
10
25
7.25
5
15
7.12
• pH below 6.9 probably requires
bicarbonate
2.5
15
6.88
It is generally agreed that:
• pH above 7.0 requires NO bicarbonate
If you give HCO3 rapidly IV:
• Serum HCO3 will rise
Rapid IV administration of
bicarbonate in DKA can cause a
respiratory acidosis in the brain
• 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
8
Is Bicarbonate Really
Hyperosmolar?
N Engl J Med 2001;344:264-9
• Osmolarity = 2 x Na + Glu/18 + BUN/2.8
• Na is in meq/L
• Na HCO3 = 1 meq/ml or 1000 meq/L
• Osm Na HCO3 = 2 x 1000 = 2000 mOsm!
Push Bicarb ONLY For:
• Hyperkalemic emergency
Phosphate Therapy
in DKA
• Impending cardiopulmonary arrest
Phosphate Therapy in DKA
• No proven benefit
• Rarely used in adults
NKHC, HONK
• Up to ½ of K requirements given as
K2 PO4 in pediatric patients.
• Check with your pediatrician
9
5 Actions of Insulin
• Drive Glucose into cell
→ Glu ↑
Nonketotic Hyperosmolar Coma
(NKHC, HONK)
• Not enough insulin to move glucose
• Drive K into cell
→K↑
• Anabolic
→ Catabolic
• Enough insulin to block catabolic state
• Block Fat breakdown
→ FFA ↑
• Enough to not breakdown fat & protein
• Block protein breakdown → Keto Acids ↑
Nonketotic Hyperosmolar Coma
(NKHC)
Insulin levels
Ketoacidosis
Glucose
HCO3
OSM
Age
Onset
Associated diseases
Seizures
Coma
Mortality
DKA
very low
profound
600
5
300 - 325
young
acute
rare
very rare
rare
approaches 0
NKHC
may be normal
minimal
1,000
20 - 24
350+
old
chronic
common
common
common
20 - 40%
NKHC/HONK
• Volume resuscitate NSS
• Slow fluids to 200-250cc/hr
• Use NSS if corrected Na < 135
• Use ½ NSS if Na corrects > 135
• Enough insulin to drive K into cell
• Extreme glucose elevations
NKHC
• AMS in most patients
• Up to 50% present in deep 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
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, go slower
• KCI at about 10meq/hr
10
• 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
Hypoglycemia
Hypoglycemia ReExPLAIND
Re
Ex
P
L
A
I
N
D
Renal
Exogenous Insulin/antihyperglycemics
Pituitary Insufficiency
Liver
Alcohol, Addison’s, Aspirin
Infection, Insulinoma
Neoplasm
Drugs
Treating NKHC
• Twice the volume deficit, but
Treat ½ as aggressively as DKA
• Tease with insulin, no drip
• DKA pts should never die, NKHC often do
Why does every hypoglycemic
patient’s low blood glucose have to
be ReExplained?
Hypoglycemia (Renal)
• Decreased insulinase
• Decreased excretion
• Decreased caloric intake
• Increased number of infection
11
Hypoglycemia (Drugs)
• Beta Blockers
• Alcohol
• Aspirin
• Pentamidine
One amp of D50 should raise
serum glucose by about 200
mg/dl for up to 30 minutes.
If it doesn’t look for
complicating factors like
sepsis, insulin OD, oral agent
OD, or ASA OD
• Valproic Acid
One Amp of D50
• 50% Dextrose in Water
• 50 cc of 50% = 25 grams
• 100 calories
Dextrose does not last too long reliably,
But in first 5-10 minutes will raise
glucose by about 200 mg%
• Lasts 5-30 minutes reliably
• After 30 minutes: feed or D5W
D50 Mistakes
• Not needed
Glucose Dosing
• Adult
D50 1 cc/kg
• No secure IV line
• Child
D25 2 cc/kg
• Pushed too quickly
• Neonate
D10 2-4 cc/kg
• Repeated too quickly
• Given in too young a patient
12
Hypoglycemic But No IV
Ann Emerg Med 1991;20:375-379
• Oral Glucose Gel
•
•
•
•
•
• Glucagon IM
Ann Emerg Med 2000;36:133-138
• Decreased Hypoglycemic episodes by a factor of 27
• D50 rarely required post octreotide
• Stabilization was immediate
Glucagon stimulates cAMP and block insulin
Can be given IM if no IV available
1.0 mg IM will elevate glucose about 100 mg%
Onset of action is 5-15 minutes
Effective 50-98% of the time
The signs and symptoms of
hypoglycemia are variable and
are dependent on both:
– Low Glucose Levels
– Rate of Fall of Glucose
Always Check Glucose
Nobody dies of hyperglycemia
They do from Hypoglycemia
• AMS
• Seizures
• Post-ictal
• CVA
• Weak, Dizzy
13
Therapy and Rationales in DKA
• Volume
Summary
– Enough to re-hydrate
– But don’t wash out ketones
• Insulin
– Saturate receptors
– And keep saturated
• Potassium
– Avoid hyperkalemia early
– But avoid hypokalemia later
Therapy and Rationales in DKA - 2
Volume Therapy in DKA
Begin Therapy:
• Bicarbonate
– Rarely needed
– Use for decompensation
• Phosphate
– Only cachectic patients
– Use for values below 1.0 – 1.5
Refractory Acidosis in DKA
• Dead Gut
• Bolus healthy patients with at least
1,000 cc of NSS (20 cc/kg) rapidly
Stable Patients:
• NSS at 500 cc/hr x 4 hours
• Switch to NSS at 250 cc/hour
Profound Dehydration:
• NSS wide open until well perfused
NKHC/HONK
• Volume resuscitate NSS
• Slow fluids to 200-250cc/hr
• Sepsis
• Use NSS if corrected Na < 135
• Abscess
• Use ½ NSS if Na corrects > 135
• KCI at about 10meq/hr
14
Hypoglycemia ReExPLAIND
Re
Ex
P
L
A
I
N
D
Renal
Exogenous Insulin/antihyperglycemics
Pituitary Insufficiency
Liver
Alcohol, Addison’s, Aspirin
Infection, Insulinoma
Neoplasm
Drugs
Summary
• DKA - fluid bolus
- NSS, insulin, K
• Beware Hypokalemia in DKA
• Go slow in HONK
• Re-explained all hypoglycemia
• Check glucose
15