Hyperglycemic Emergency: DKA and HHS - AAFP Home · 2020-04-24 · 1 Hyperglycemic Emergency: DKA and HHS Heather C. Kovich, MD ACTIVITY DISCLAIMER The material presented here is

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Hyperglycemic Emergency: DKA and HHS

Heather C. Kovich, MD

ACTIVITY DISCLAIMERThe material presented here is being made available by the American Academy of Family Physicians for educational purposes only. Please note that medical information is constantly changing; the information contained in this activity was accurate at the time of publication. This material is not intended to represent the only, nor necessarily best, methods or procedures appropriate for the medical situations discussed. Rather, it is intended to present an approach, view, statement, or opinion of the faculty, which may be helpful to others who face similar situations.

The AAFP disclaims any and all liability for injury or other damages resulting to any individual using this material and for all claims that might arise out of the use of the techniques demonstrated therein by such individuals, whether these claims shall be asserted by a physician or any other person. Physicians may care to check specific details such as drug doses and contraindications, etc., in standard sources prior to clinical application. This material might contain recommendations/guidelines developed by other organizations. Please note that although these guidelines might be included, this does not necessarily imply the endorsement by the AAFP.

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DISCLOSUREIt is the policy of the AAFP that all individuals in a position to control content disclose any relationships with commercial interests upon nomination/invitation of participation. Disclosure documents are reviewed for potential conflict of interest (COI), and if identified, conflicts are resolved prior to confirmation of participation. Only those participants who had no conflict of interest or who agreed to an identified resolution process prior to their participation were involved in this CME activity.

All individuals in a position to control content for this session have indicated they have no relevant financial relationships to disclose.

The content of my material/presentation in this CME activity will not include discussion of unapproved or investigational uses of products or devices.

Heather C. Kovich, MDFamily 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.

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Learning Objectives1. 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 SystemStep 1 Step 2 Step 3

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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

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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: ChemistryLab 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

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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 CBCLab 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

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• 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

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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

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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

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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

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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

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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

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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

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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

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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

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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


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

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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

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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

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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

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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



Chloride 109 mEq/L 98‐107

Potassium 3.1 mEq/L 3.5 – 5.5

Bicarb 10 mEq/L 22‐30

Case 2: LabsLab Value Ref Range

Serum Ketones

Trace Positive

Negative

Urine Bacteria

4+ 0

Urine WBC 4+ 0

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AES Question #4

Appropriate next steps include all except the following:

A. NS bolusB. Start IV KCl @ 20-30 meq/hrC. Get a VBGD. Give 10u regular insulin bolusE. 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

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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.

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Lab Value Ref Range



Potassium 3.7 mEq/L 3.5‐5.1


CO2 5 mEq/L 22‐30


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.

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AES Question #5

Appropriate next steps includeA. 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.

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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

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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




Potassium 5.8 mEq/L 3.5 – 5.1

Bicarbonate 26 mEq/L 22‐30


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

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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

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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

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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


• 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

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• Cerebral edema is a potentially fatal complication in

children and young adults

– Take headaches seriously

• HHS patients have higher mortality than DKA patients

Questions

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Contact Information

Heather Kovich, MD

[email protected]

@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.

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Hyperglycemic Emergency: DKA and HHS - AAFP Home · 2020-04-24 · 1 Hyperglycemic Emergency: DKA and HHS Heather C. Kovich, MD ACTIVITY DISCLAIMER The material presented here is