diabetic ketoacidosis hyperglycemic hyperosmolar state

Management Guideline for

Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State
in Children and Adolescents

2560

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 diabetic ketoacidosis hyperglycemic hyperosmolar state

Management Guideline for Diabetic Ketoacidosis (DKA)

and Hyperglycemic Hyperosmolar State (HHS)
in Children and Adolescents

DKA
(acidosis) (ketonemia)
(hyperglycemia) (insulin)

DKA
1. (glucose)

glycogenolysis gluconeogenesis

2. Ketosis (lipolysis) (ketogenesis)

(ketonuria)
3. (hypertriglyceridemia)
(free fatty acid)
4. Osmotic diuresis (glycosuria)

(electrolyte imbalance)
5. (dehydration)
(osmotic diuresis)

DKA
1 (type 1 diabetes)
DKA

Kussmaul breathing (metabolic acidosis)

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 diabetic ketoacidosis hyperglycemic hyperosmolar state

(polydipsia)
(polyuria) (nocturnal enuresis)
(polyphagia)
(weight loss) (fatigue)

DKA
1. : (plasma glucose) >200 ./. (11
/)
2. (acidosis): HCO3 <15 / venous pH <7.3
3. (-hydroxybutyrate, BOHB >3 /) /
( >2+)

DKA
DKA


Venous pH 7.20-7.29 7.10-7.19 <7.10
Serum bicarbonate (/) 10.0-14.9 5.0-9.9 <5

1.
1.1
1.2 (assessment of clinical severity of dehydration)
DKA 5-10%

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 diabetic ketoacidosis hyperglycemic hyperosmolar state

(3-5%)
(5-7%)* skin turgor
(7-10%) skin turgor (hyperpnea)
capillary refill 2
(>10%)
* 1 -5 : 5% dehydration capillary refill 2
skin turgor
DKA
underestimate DKA
DKA severe DKA (7-10%) moderate DKA
(5-7%) ( DKA)
1.3
Blood glucose blood ketone BOHB ()
Urine ketone glucose
BUN, serum creatinine, electrolytes, calcium, phosphate, magnesium, albumin
Venous blood gases pH, pCO2 base excess
EKG (
)
2. DKA
2.1 CBC
2.2 (hemoculture)
2.3 (urinalysis) (urine culture)
2.4 (chest X-ray)
3.
3.1 Hemoglobin A1c (HbA1c)
3.2 Insulin C-peptide ( insulin)
3.3 Glutamic acid decarboxylase antibody (anti-GAD), islet antigen 2 antibody (IA2),
insulin autoantibody (IAA), islet cell antibody (ICA), zinc transporter 8 antibody
(ZnT8A)
3.2 3.3 ()

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 diabetic ketoacidosis hyperglycemic hyperosmolar state

DKA
1.
2. metabolic acidosis ketosis
3.
4. DKA
5. DKA

DKA
1.
1.1 DKA DKA
DKA 5-10%
deficit DKA
DKA (%)
Mild 3-5
Moderate 5-7
Severe 7-10
1.2 0.9% NaCl (NSS) Ringers lactate solution (RLS)
Plasmalyte 20 ./. bolus 15-30

1.3 0.9% NaCl 10 ././. ( 1-1.5 1

) tissue perfusion 30 ./. 2
mild DKA 1.4
1.4 fluid deficit 48 maintenance fluid (
Holliday-Segar) 1.2 1.3

Rate of IV (./.) = (2 x maintenance fluid 24 .) + fluid deficit initial fluid 1.2/1.3

48

0.9% NaCl RLS Plasmalyte 4-6

( 1-3 hypernatremia 0.45% NaCl) ()

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 diabetic ketoacidosis hyperglycemic hyperosmolar state

4-6 0.45% NaCl

24
2 maintenance

( DKA osmotic diuresis)
1.5 KCl initial rehydration
/ hyperkalemia (serum K >5.5 / EKG tall peak T
K ) K 3
1.6 fluid balance
2-3
1.7 moderate severe DKA
( mild DKA )
2.
initial rehydration 1-2 regular insulin (RI)
continuous low-dose intravenous insulin infusion method
RI 0.05-0.1 /./. ( 5 0.05 /
./.) insulin infusion RI 50 0.9% NaCl 50 .
1 . RI 1 insulin infusion infusion pump
side-line
infusion set insulin infusion 30 .
saturate binding site

1. IV bolus insulin insulin infusion
hypokalemia
2. initial rehydration RI infusion
50-200 ./. dehydration RI
50-100 ././.
bedside blood glucose 1

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 diabetic ketoacidosis hyperglycemic hyperosmolar state

250-300 ./. 5% dextrose

5% dextrose in 0.45% NaCl
insulin infusion acidosis ketonemia
dextrose
150-250 ./. ( 150 ./.)
acidosis ketonemia dextrose 7.5-12.5%
RI RI 0.05 /./.
metabolic acidosis
0.05 /./. 0.03 /./.

0.01 /./.
70 ./. 10% glucose 2 ./.
dextrose

1. insulin infusion rapid-acting insulin analog
RI insulin infusion rapid-acting insulin
analog aspart lispro glulisine rapid-acting insulin analog
insulin infusion 15-30 0.5-1 RI
rebound hyperglycemia (
DKA)
2. insulin infusion infusion pump
insulin intramuscular (IM) subcutaneous (SC)
rapid-acting insulin analog RI 0.3 /. 0.1
/. 1 0.15-0.20 /. 2
250 ./. DKA 0.05 /. 1
severe DKA (severe acidosis, peripheral perfusion
) 5
3. (potassium, K)
DKA total body K
K K K
K EKG tall peak T
K initial rehydration insulin infusion K

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 diabetic ketoacidosis hyperglycemic hyperosmolar state

40 / (<2.5 /) K
initial rehydration ( K 0.5 /./.)
(serum K >5.5 /) K

K <2.5 / KCl 0.5 /./. RI
infusion K >2.5 / EKG KCl
K 0.5 /./.
K2HPO4/KH2PO4 KCl

K
hypokalemia K KCl
K
4. (sodium, Na)
DKA (pseudohyponatremia)
corrected serum sodium

Corrected Na = Na (mmol/L) + [Plasma glucose (mg/dL) 100] x 1.6

100

corrected serum Na 150 /

hypernatremia hyperosmolality Na glucose
osmolality
osmolality, serum Na, vital signs, consciousness, coma score

48-72 24
200-300 ./. Na
0.9% NaCl Na
Na 0.9% NaCl
0.45% NaCl
DKA triglyceride
pseudohyponatremia Na

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 diabetic ketoacidosis hyperglycemic hyperosmolar state

blood glucose 600 ./. corrected Na osmolality

osmolality 320 mOsm/kg H2O
5. bicarbonate (HCO3)
5.1 acidosis dehydration insulin
bicarbonate HCO3
K bicarbonate life-threatening
hyperkalemia acidosis (pH <6.9) NaHCO3 1-2 /.
intravenous drip 1
5.2 bicarbonate cerebral edema, paradoxical
cerebral acidosis, shift to the left of oxyhemoglobin dissociation curve peripheral oxygen
availability severe hypokalemia K
EKG
6. (phosphate, PO4)
DKA acidosis

DKA
(hypocalcemia) 1 ./.
K2HPO4/
KH2PO4 20-30 / KCl

7.
DKA
ICU ( )
cerebral edema ( 5 severe acidosis, pCO2 BUN )

7.1 Vital signs neurological signs 1

7.2 Bed-side blood glucose 1
7.3 Serum electrolytes, blood gases () 2-4
7.4 Intake output 2-4
7.5 Serum ketone urine ketone 4-6 DKA
7.6 BUN, serum Cr, Ca P severe DKA
7.7 flow chart
7.8 nasogastric tube urinary catheter
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 diabetic ketoacidosis hyperglycemic hyperosmolar state

8. DKA
DKA

urinalysis, urine culture, hemoculture, tuberculin test

9.
DKA
9.1 Hypoglycemia continuous insulin infusion
150 ./.
continuous insulin infusion
9.2 Persistent acidosis HCO3 <10 /
8-10 hyperglycemia
- (RI <0.05-0.1 /./.)
intravenous infusion
-
-
- hyponatremia hypokalemia
- (
)
9.3
hyperchloremia hyperchloremic metabolic acidosis
ketoacidosis BOHB
RLS strength Na K2HPO4/KH2PO4 KCl
9.4 Hypokalemia K acidosis
K K ( 3) K
K muscle weakness
9.5 (cerebral edema)
4-12
5 bicarbonate pCO2
BUN 4

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 diabetic ketoacidosis hyperglycemic hyperosmolar state

Decreased sensorium, disorientation, agitation
pupillary change, ophthalmoplegia,
papilledema

(diagnostic criteria)
Abnormal motor verbal response to pain
Decorticate decerebrate posture
Cranial nerve palsy ( III, IV VI)
Abnormal neurogenic respiratory pattern ( grunting, tachypnea, Cheyne-Stokes
respiration, apneusis)
(major criteria)
Altered mentation/fluctuating level of consciousness
Sustained heart rate deceleration ( 20 /) intravascular
volume
Age-inappropriate incontinence
(minor criteria)


Lethargy not easily arousable
Diastolic blood pressure >90 mmHg
5
1 2
1 2 4%
92%

- 30o
- 2/3
- 20% mannitol 0.5-1 /. (2.5-5 ./.) 10-15
30 2

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 diabetic ketoacidosis hyperglycemic hyperosmolar state

- mannitol hypertonic saline (3% NaCl) 2.5-5 ./.

10-15
- Intubation keep pCO2 30-35 mmHg
aggressive hyperventilation
- Monitor neurological signs brain CT stabilize

DKA
1. 12-24 (
) metabolic blood glucose <300
./. pH >7.3 serum HCO3 >15 / ketosis (BOHB <1 /)
mild acidosis
maintenance + deficit
2. insulin infusion resolution DKA venous pH >7.3, serum
HCO3 >15 / BOHB <1 / RI
0.25-0.5 /. RI
0.5-1 RI 6
basal-bolus regimen DKA rapid-acting insulin
analog 0.25-0.5 /. basal insulin ( glargine detemir)
15-30 ( 3 )
3.

- basal-bolus regimen 24 (total daily dose,
TDD) 1.0-1.5 /./ 1.0-2.0 /./
TDD basal insulin ( glargine detemir) rapid-
acting insulin analog ( rapid-acting insulin analog
15-20% TDD)
- conventional regimen RI intermediate acting insulin (NPH)
TDD 2 3 ( NPH :
RI 2 : 1) 1 3 ( NPH : RI 1 : 1)
regimen DKA
4. balanced diet
50-55 25-30 15-20
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 diabetic ketoacidosis hyperglycemic hyperosmolar state

5.
blood glucose (self-monitoring of blood glucose, SMBG) 4-5
- 3 hypoglycemia urine
ketone blood glucose >300 ./.
70-180 ./.
6. DKA

6.1
6.2 Insulin insulin
6.3
6.4
6.5 hypoglycemia hyperglycemia
6.6
6.7

6.8

1-2
7. anti-GAD, IA2
2 C-peptide C-peptide <0.6 ng/mL
1

hyperglycemic hyperosmolar state (HHS)

1. : >600 ./. (33.3 /)
2. Arterial pH >7.3 venous pH >7.25
3. Serum bicarbonate >15 /
4.
5. Effective serum osmolality >320 mOsm/kg H2O
Effective serum osmolality = (2 x plasma Na) + (plasma glucose (mg/dL)/18)
6. ( 50)

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 diabetic ketoacidosis hyperglycemic hyperosmolar state

HHS
HHS type 2 diabetes, type 1 diabetes
neonatal diabetes type 1 diabetes HHS
HHS DKA HHS
DKA acidosis lactic acidosis hypoperfusion
HHS DKA HHS
osmolality osmotic diuresis
HHS
DKA ICU
1.
1.1 initial bolus 0.9% NaCl >20 ./. 1-2 perfusion

1.2 fluid deficit 12-15% 0.45-0.75% NaCl 24-48
osmolality hemodynamic 0.9% NaCl
1.3 ( 0.5
//.)
1.4 75-100 ././.
1.5 2-3 >90 ././. 2.5%
5% dextrose
1.6 0.45% NaCl Na

2.
2.1 50 ././.
HHS
circulatory compromise thrombosis
hypokalemia K severe ketosis acidosis

2.2 RI IV infusion 0.025-0.05 ././. 50-75
././.
2.3 insulin bolus
3.
3.1 serum K adequate renal function KCl 40 /
3.2 serum K 2-3
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 diabetic ketoacidosis hyperglycemic hyperosmolar state

4. bicarbonate HHS hypokalemia

tissue oxygen delivery
5. K2HPO4/KH2PO4 KCl severe hypophosphatemia
rhabdomyolysis, hemolytic anemia, muscle weakness paralysis
6. rhabdomyolysis acute kidney failure, severe
hyperkalemia, hypocalcemia muscle swelling
creatine kinase 2-3

1. Wolfsdorf JI, Allgrove J, Craig ME, Edge J, Glaser N, Jain V, et al. ISPAD Clinical Practice
Consensus Guidelines 2014. Diabetic ketoacidosis and hyperglycemic hyperosmolar state.
Pediatr Diabetes 2014;15 Suppl 20:154-79.
2. Watts W, Edge JA. How can cerebral edema during treatment of diabetic ketoacidosis be
avoided? Pediatr Diabetes 2014;15:271-6.
3. Umpierrez G, Korytkowski M. Diabetic emergencies - ketoacidosis, hyperglycaemic
hyperosmolar state and hypoglycaemia. Nat Rev Endocrinol 2016;12:222-32.

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 diabetic ketoacidosis hyperglycemic hyperosmolar state

diabetic ketoacidosis (DKA)

Moderate/Severe DKA*
Resuscitation and initial rehydration
- Airway NG tube
- Breathing (100% oxygen)
- Circulation: 0.9% NaCl 10-20 ./. 1 . ( 1-1.5 )
tissue perfusion ( 30 ./. 2 . )

IV therapy Insulin therapy

- fluid deficit 5-10% 48 . initial rehydration 1-2 .
0.9% NaCl 4-6 . regular insulin (RI)
- Monitor EKG for abnormal T wave continuous low-dose IV infusion
- KCl IV fluid 40 / ( serum K >5.5 0.05-0.1 /./.
/ K )

- Bed-side blood glucose (BG) 1 .
- Fluid input & output, vital signs neurological signs 1 . ( DKA)
- Serum electrolytes 2-4 . ( BUN, serum Cr, Ca P severe DKA)
- Monitor EKG T wave ()
- Serum ketone urine ketone 4-6 . DKA

acidosis / Warning neurological signs BG <300 ./.

HR

IV therapy
- IV fluid
- hypoglycemia 5% D/NSS/2 5% D/NSS
cerebral edema
-
Improvement

Management
- Admit ICU, monitor neurological signs
- 30o Transition to SC insulin
- IV 2/3 IV insulin
- 20% mannitol 2.5-5 ./. IV 10-15 SC insulin
( mannitol 3% NaCl 2.5-5 ./. IV 10-15 )
- Intubation
- brain CT stabilize
* mild DKA IV initial rehydration IV therapy 16
Wolfsdorf JI, et al. Pediatr Diabetes 2014;15 Suppl 20:154-79.