1. 1
Hyperglycemic Emergency:
DKA and HHS
Heather C. Kovich, MD
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2. 2
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Heather C. Kovich, MD
Family physician, Northern Navajo Medical Center, Shiprock, New Mexico
Dr. Kovich earned her medical degree from Temple University School of
Medicine in Philadelphia, Pennsylvania, and completed her family
medicine residency at the University of Washington in Seattle. Since 2009,
she has worked in the rural setting of Shiprock, New Mexico. She has
authored or coauthored a number of articles, including a perspective on
the challenges facing patients and physicians in the rural United States
that was published in The New England Journal of Medicine in 2017.
3. 3
Learning Objectives
1. Differentiate hyperglycemia from diabetic ketoacidosis (DKA) and
hyperosmolar hyperglycemic state(HHS).
2. List the evaluation for a patient with hyperglycemia.
3. Describe the treatment for DKA and HHS.
4. Describe the differences in the treatment of DKA in adults and in
patients less than 20-years of age.
5. Identify the differences between mild, moderate and severe DKA.
Audience Engagement System
Step 1 Step 2 Step 3
4. 4
Case 1: History
• 43 year old man
• PMHx:
– Insulin-dependent type 2 diabetes
– Hypertension
– Polysubstance abuse (alcohol, methamphetamine)
– Obesity
– Non-compliance
Case 1: Presentation
• Presents to ED c/o 3-4 days of
– increased thirst and urination
– nausea and vomiting
– sore throat
– dyspnea
• Has not taken his medicine for two weeks,
was binge-drinking alcohol, then switched to
methamphetamine
5. 5
Case 1: Exam
• Vitals:
– Temp: 95.9 F
– HR: 121
– RR: 18
– BP: 130/86
– SpO2: 99% RA
• On exam he was somnolent but arousable, oriented x 3. He
had dry mucus membranes. Lungs were clear but he had
increased respiratory effort and Kussmaul-type breathing. His
abdomen was soft and nontender.
Lab Value Ref Range
Glucose 688 mg/dl 74‐106
Sodium 129 mEq/L 137‐145
Potassium 6.0 mEq/L 3.5‐5.1
BUN 27 mg/dl 7‐20
Creatinine 2.3 mg/dl 0.3‐1.2
Chloride 91 mEq/dl 98‐107
CO2 <5 mEq/L 22‐30
Case 1: Chemistry
Lab Value Ref Range
Magnesium 2.4 mg/dl 1.6‐2.3
Phos 8 mg/dl 2.5‐4.5
Ethanol <10 mg/dl <10
Ketones Positive Negative
Lipase 650 u/L 0‐160
Anion gap 33 4‐12
6. 6
Lab Value Ref Range
pH 6.99 7.35‐7.45
pCO2 7.8 mm Hg 35‐45
pO2 113 mm HG 66‐75
Bicarb 3 mEq/L 22‐26
Case 1: ABG and CBC
Lab Value Ref Range
WBC 15 k/ul 3.5‐11
Neutrophils 91% 40‐80
Hgb 17 g/dl 11.7‐15.7
Hct 51% 35‐47
Platelets 330 k/ul 150‐400
AES Question #1
What is the best diagnosis?
A. Hyperglycemic hyperosmolar syndrome
B. Severe Diabetic Ketoacidosis
C. Sepsis
D. Alcoholic Ketoacidosis
E. Mild Diabetic Ketoacidosis
7. 7
• HHS: hyperglycemia, hyperosmolality, dehydration, absence of
ketoacidosis
• Sepsis: infection and organ dysfunction
• AKA: clinical presentation similar to DKA, lower sugars
• Mild / Moderate / Severe DKA:
– Mental status
– Degree of acidosis (AG/pH/serum bicarb)
– Severe = AG>12; pH <7; Bicarb <10
DKA definition
• D: Serum glucose >250
• K: Elevated serum ketones
• A: pH < 7.3; serum bicarbonate < 18 meq/L
8. 8
DKA
Insulin Catecholamines,
cortisol, GH, glucagon
Lipolysis
FFA production
Hyperglycemia
“ketoacids”
• Acetoacetate
• B‐hydroxybutyrate
(not a keto)
• Acetone
(not an acid)
Anion Gap
• Serum anion gap = Na - (Cl + HCO3)
– Normal values usually
– 4-12 but depends on lab
• Disorders that produce acids, e.g. ketoacids,
produce an anion gap
– Other metabolic acidoses are hyperchloremic
9. 9
Kussmaul breathing
• Compensatory hyperventilation in metabolic
acidosis
• Deep breathing
– Rate can be fast, normal, or slow
Normal Vs. Kussmaul
Causes of DKA
• Illness
– Infection
– Physiologic stressors, e.g. pancreatitis, MI
• Inadequate exogenous insulin
– New onset diabetes
– Discontinuation of insulin
• Drugs
– Cocaine
– Steroids, antipsychotics, SGLT2 inhibitors, etc
• SGLT2 inhibitors associated with euglycemic DKA
10. 10
Type 2 diabetics get DKA
• 20-50% of DKA is in type 2 diabetics
• Hospitalizations for DKA are increasing
• Not all Type 2 with DKA need indefinite insulin
treatment
• 5-10% of diabetes
• destruction of beta cells
• usually autoimmune
• absolute insulin deficiency
• may have insulin resistance
Type 1 Vs Type 2
• 90% of diabetes
• insulin resistance and
deficiency
• beta cell dysfunction common
11. 11
Special Hybrids
• LADA: Latent Autoimmune Diabetes of Adults
– Adults, type 2, have beta cell antibodies, require
insulin within a few years
• MODY: Maturity Onset Diabetes of the Young
– No antibodies, onset <25 y.o., nonobese
– Autosomal Dominant transmission
• Pick the true statement
A. Elevated WBC makes infection
likely
B. This patient does not need
bicarbonate
C. This patient is hyponatremic
D. This patient has an excess of
potassium
E. This patient has pancreatitis
AES Question #2
• Abbreviated Labs:
– WBC 15, 91%
Neutrophils
– pH 6.99; Bicarb 3
– Glucose 668
– Sodium 129
– Potassium 6
– Lipase 650
12. 12
WBC in DKA
• Most patients with DKA and HHS present with leukocytosis
• Due to hypercortisolemia and catecholamines
• Proportional to the degree of ketonemia
• WBC > 25k, or more than 10% bands increases suspicion for
infection
Sodium Correction
• Hyperglycemia pulls water out of the cells, and reduces the
plasma Na concentration
• Na ↓ 2 mEq/L for each 100 mg/100 mL ↑ in glucose
• Insulin drives glucose and water into the cells, raising the
serum sodium concentration
• Use uncorrected sodium for anion gap calculation
13. 13
Potassium deficiency in DKA
• Usually total body deficiency of 300-600 mEq due to
increased urinary losses
• Hyperosmolality and insulin deficiency pushes K
extracellular
• Only 5% DKA patients present with low serum K
Bicarbonate replacement
• No benefit with pH >6.9
• At pH < 6.9 - lack of data and consensus
• ADA recommends bicarb replacement when pH < 6.9
– Risk of acidosis: impaired myocardial contractility, cerebral
vasodilation, coma
– Risk of replacement: hypokalemia, decreased tissue oxygen
uptake, paradoxical worsening of ketosis, decreased respiratory
drive
14. 14
Pancreatitis and DKA
• Pancreatitis is common in DKA (10%) but
– 20% of patients with DKA have elevated amylase
and lipase without any symptoms of pancreatitis
– Elevated pancreatic enzymes don’t correlate to
symptoms or imaging
DKA: Principles of Treatment
• Correct fluid deficit
• Correct electrolyte abnormalities
• Administer insulin
15. 15
Fluids
• Isotonic crystalloids first in order to
– Expand extracellular volume, stabilize
cardiovascular status
– Increase insulin responsiveness by
• improving perfusion
• reducing stress hormone levels
• No data for specific crystalloid
– UK NICE and ADA guidelines = normal saline
Fluids
• After initial NS replacement, fluids depend on
– State of hydration and urine output
– Electrolyte levels
• low serum sodium ⇢ NS at 250-500 cc/hr
• normal/high sodium ⇢ ½ NS at 250-500 cc/hour
• use ½ NS if adding potassium
– Blood glucose:
• add dextrose when the serum glucose reaches 200-
250 mg/dL
16. 16
Insulin
• Give insulin if K > 3.3 mEQ/L
• No data to favor:
– Regular insulin or rapid acting analog
– Bolus or no bolus
– SQ (q1-2 hr rapid acting) or continuous infusion
• Both ADA and NICE guidelines favor infusion
– Weight-based rate vs sliding scale with target
glucose reduction 50-70 mg/dl/hr
Lab Value Ref Range
Glucose 268 mg/dl 74‐106
CO2 10 mEq/L 22‐30
Potassium 3.7 mEq/L 3.5 ‐5.1
Magnesium 1.9 mg/dl 1.6‐2.3
PO4 1.3 mg/dl 2.5‐4.5
Calcium 7.5 mg/dl 8.4 – 10.2
Albumin 3.0 g/dl 3.5 – 5.5
AES Question #3
This patient requires
repletion of
A. Phosphate
B. Potassium
C. Calcium
D. Magnesium
Patient receives 4L NS and a continuous infusion of regular insulin
17. 17
Potassium replacement
• Wait to add K to fluids until
– Serum K < 5.2
– Urine output is established
Phosphate repletion in DKA
• Most DKA patients have phosphate deficiency
– Most (94%) present with high serum levels
– Rapidly declines w/ volume expansion and insulin
– Asymptomatic hypophosphatemia gradually resolves
without intervention
18. 18
Phosphate repletion
• Don’t replete unless
• severe hypophosphatemia (<1.0 mg/dl)
• cardiac/respiratory dysfunction
• hemolytic anemia
• Prospective RCTs = no benefit to repletion
• Risk of repletion = hypocalcemia, hypomagnesemia
Resolution of DKA
• Glucose <200 and
• 2 out of 3
– Venous pH >7.3
– Bicarb ≥15
– Anion gap ≥ 12 (or normal B-hydroxybutyrate levels)
• Hyperglycemia resolves faster than ketoacidosis
19. 19
Case 1: Learning Points
• DKA common in Type 2 diabetes
• Don’t diagnose infection only by WBC
• Don’t diagnose pancreatitis only by enzymes
• Correct the sodium with math, not fluids
• No data for bicarbonate repletion
• No data for phosphate repletion
Case 2
• 25 yo woman no significant PMHx presents with
– Dysuria and frequency for at least 2 weeks
– Chills, flank pain, nausea, and vomiting x 2 days
– Weakness, dry mouth, polyuria
20. 20
Case 2: Exam
• Vitals
– Temp: 100.1
– HR: 105
– RR: 22
– BP: 100/62
– SpO2: 98
– WT: 215 lb
• On exam she is alert and oriented. She has a noticeable fruity
smell. Her mucus membranes and skin are dry. She has mild
CVA tenderness.
Lab Value Ref Range
WBC 19 k/ul 4‐10
Glucose 440 mg/dl 74‐106
Sodium 138 mEq/L 135‐145
Chloride 109 mEq/L 98‐107
Potassium 3.1 mEq/L 3.5 – 5.5
Bicarb 10 mEq/L 22‐30
Case 2: Labs
Lab Value Ref Range
Serum
Ketones
Trace
Positive
Negative
Urine
Bacteria
4+ 0
Urine WBC 4+ 0
21. 21
AES Question #4
Appropriate next steps include all except the
following:
A. NS bolus
B. Start IV KCl @ 20-30 meq/hr
C. Get a VBG
D. Give 10u regular insulin bolus
E. Get blood and urine cultures
• Hold insulin until K > 3.3
• If K is low, start KCl at 20-30 mEq/hr
– If peripheral line used, can get pain/phlebitis > 10mEq/hr
• Okay to get VBG instead of ABG in stable patients
without respiratory failure
• If infection is suspected, get blood and urine
cultures
22. 22
Serum ketones
• Why were ketones only trace positive in a
patient who smells like acetone?
– Nitroprusside test for acetoacetate +/- acetone
– Nitroprusside does not test for B-hydroxybutyrate
• B-hydroxybutyrate is predominant in DKA
• 10:1 B-hb:acetoacetate ratio in severe or prolonged
DKA
Case 3
• A 15-year-old female presents with a 1-week history of polyuria
and polydipsia.
• Examination
– BP 90/66 mm Hg
– HR 120 beats/min
– RR 32/min, Kussmaul-type
– Lethargic, volume-depleted female with the smell of acetone on her breath.
23. 23
Lab Value Ref Range
Glucose 525 mg/dl 74‐106
Sodium 129 mEq/L 137‐145
Potassium 3.7 mEq/L 3.5‐5.1
Chloride 99 mEq/L 98‐107
CO2 5 mEq/L 22‐30
Case 3: Labs
Lab Value Ref Range
pH 7.05 7.35‐7.45
pCO2 7 mm Hg 35‐45
pO2 98 mm Hg 66‐75
Case 3
• Fluids, potassium, and insulin are started per protocol
• 6 hours later the ICU calls to ask for a Tylenol order
because the patient has a headache and to place a
foley because the patient has been incontinent.
• On exam, the patient is still lethargic and is moaning
that her head hurts. She opens her eyes only with
repeated commands. She is not oriented to place.
24. 24
AES Question #5
Appropriate next steps include
A. 1 L bolus of NS
B. 650 mg acetaminophen
C. Mannitol 0.5 g/kg IV over 20 minutes
D. 6 mg SQ sumatriptan
Cerebral edema in DKA
• More common in children and young adults
• More common with more severe acidosis
• No evidence on how to prevent
• Role of imaging is controversial
– Many/most children with DKA will have narrowing of ventricles
• Treatment includes mannitol, hypertonic saline, and
intubation, but there is no evidence-based treatment
protocol.
25. 25
Diagnosis of Cerebral Edema
• Any diagnostic criteria; OR 2 major + 1 minor; OR 1 major +2 minor
• Diagnostic Criteria = signs of cerebral injury
– Abnormal motor or verbal response to pain
– Decorticate or decerebrate posturing
– Abnormal pupillary response or CN palsy
– Abnormal respiratory pattern: grunting, Cheyne-Stokes, apnea
• Major Criteria
– Deteriorating mental status
– Inappropriate relative bradycardia
– Incontinence inappropriate for age
• Minor Criteria
– Headache
– Vomiting
– Lethargy
– Elevated blood pressure
Cerebral Edema in DKA
• Recent RCT comparing rates and tonicity of fluid
resuscitation did not show difference in rate of edema
– 350 kids in each of 4 arms
• NS rapid repletion
• ½ NS rapid repletion
• ½ NS slow repletion
• NS slow repletion
– 50 patients with decline in GCS
– 12 with clinically apparent cerebral injury who received
hypertonic therapy, intubation
26. 26
Case 4
• A 80-year-old woman is brought to the emergency department
unconscious. The examination is unremarkable except for
very dry skin and mucous membranes.
– T 38.1°C (100.6°F)
– BP 89/43 mm Hg,
– HR 128 beats/min,
– RR 15/min.
Lab Value Ref Range
Glucose 970 mg/dl 74‐106
Sodium 150 mEq/L 137‐145
Chloride 112 mEq/L 98‐107
Potassium 5.8 mEq/L 3.5 – 5.1
Bicarbonate 26 mEq/L 22‐30
Case 4: Labs
Lab Value Ref Range
Creatinine 4.8 mg/dl 0.6‐1.2
BUN 80 mg/dl 8‐25
Ketones Trace pos Negative
Anion Gap 12 4‐12
S Osm (calc) 382 275‐295
27. 27
Case 4
• After 2 hours and 2 L IV NS the patient has had
negligible urine output.
• Next steps in management include:
a) 1 L NS/ 1 hour
b) Furosemide 20 mg IV push
c) NS with 40 meq KCl
d) D5W with 3 amps Sodium Bicarb @250 cc/hr
Hyperosmolar Hyperglycemic State
• HHS has replaced the terms
– Hyperglycemic hyperosmolar nonketotic coma
– Hyperglycemic hyperosmolar nonketotic state
• Defined by
– Plasma glucose level >600 mg/dL
– Arterial pH >7.30
– Serum bicarbonate level >15 mEq/L
– Effective serum osmolality >320 mOsm/kg
– Anion gap >12
– Mild or no ketosis
– A stuporous or comatose state
28. 28
HHS
• Mortality higher in HHS (10-50%) than DKA (1.2% to 9%)
• Infections leading cause of HHS (60%)
• Coma often occurs once the serum osmolarity is greater
than 340 mOsm per kg
– Seizures occur in up to 25% of patients
• Usually 100-200 ml/kg fluid deficit – average of 9L in
adults
HHS treatment
• Treatment is similar to DKA
– Fluids/insulin/potassium
– Add dextrose to fluids when glucose reaches
300 mg/dl. Continue dextrose and insulin until
the hyperosmolality and mental status
improve
29. 29
Practice Recommendations
• DKA common in Type 2 diabetes
– Don’t always need insulin after resolution
• Don’t diagnose infection only by mildly elevated WBC
• Don’t diagnose pancreatitis only by enzymes
• Correct the sodium with math, not fluids
Practice Recommendations
• Don’t start insulin unless K > 3.3 mEQ/L
• VBG okay if no respiratory compromise
• No data for bicarbonate repletion
• No data for phosphate repletion
30. 30
Practice Recommendations
• Cerebral edema is a potentially fatal complication in
children and young adults
– Take headaches seriously
• HHS patients have higher mortality than DKA patients
Questions
31. 31
Contact Information
Heather Kovich, MD
heatherkovich@gmail.com
@heatherkovich
References
• UpToDate
– Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis
– Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment
– Cerebral edema in children with diabetic ketoacidosis
• Stoner GD. Hyperosmolar hyperglycemic state. Am Fam Physician. 2005 May 1;71(9):1723-30.
• Westerberg DP. Diabetic ketoacidosis: evaluation and treatment. Am Fam Physician 2013 Mar
1;87(5):337-46.
• Kitabchi AE et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009
Jul;32(7):1335-43.
• Nyenwe EA, Kitabchi AE. Evidence-based management of hyperglycemic emergencies in diabetes
mellitus. Diabetes Res Clin Pract. 2011 Dec;94(3):340-51.
• Kuppermann N et al. Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis. N Engl J
Med. 2018 Jun 14;378(24):2275-2287.
• Tran T et al. Review of evidence for adult diabetic ketoacidosis management protocols. Front Endocrinol.
2017 Jun 13;8:106
• Dhatariya KK, Vellanki P. Treatment of diabetic ketoacidosis (DKA)/Hyperglycemic Hyperosmolar State
(HHS): Novel Advances in the Management of Hyperglycemic Crises (UK versus USA). Curr Diab Rep.
2017 May;17(5):33.
