hyperglycemic control
in the emergency
room
Myrna Buenaluz- Sedurante
University of the Philippines
Dept of Medicine
Section of Endocrinology
Topics

Diabetic Ketoacidosis
Epidemiology
 Pathophysiology
 Diagnosis
 Treatment


Hyperosmolar Hyperglycemic State

AKA Nonketotic Hyperglycemia, Hyperosmolar Nonketotic Coma
DKA Statistics



Type 1 Diabetes
Type 1b Ketosis prone Diabetics
Occasionally in Type 2
Infection, Trauma, Cardiac
 Newly diagnosed Type 2 DM


Cost
Annual hospital cost $1 billion
 ¼ of health care dollars spent on Type 1 diabetics

DKA Mortality


Mortality primarily due to precipitating illness
Prognosis worse with old age, coma and
hypotension
HHS Statistics


<1% of all diabetes-related admissions
More common in elderly diabetics




frail
poor access to water
Decreased GFR
Mortality
Variable 10-50%
 Most often due to the precipitating illness

Role of Insulin
Ketoacidosis


Lipolysis→Increased FFA→Converted to Ketones in
Liver
Three ketones



Acetoacetic Acid; Beta-Hydroxybutyric Acid; Acetone
Accumulation leads to acidosis (↓pH) & formation of
anion gap
Differential Diagnosis
Alcoholic Ketoacidosis
 Starvation Ketosis

Diagnostic criteria
DKA
•
blood glucose >250 mg/dl,
HHS
•
blood glucose >600 mg/dl
•
•
arterial pH <7.3,
•
arterial pH >7.3,
•
•
bicarbonate <15 mEq/l, and
•
bicarbonate >15 mEq/l,
•
•
moderate ketonuria or
ketonemia
•
mild ketonuria or ketonemia, and
•
•
•
effective serum osmolality >320
mOsm/kg H2O.
longer time for development of
the disease
cytokines, markers of oxidative stress, lipid
peroxidation and cardiovascular risk
• All increased even in the absence of infection
• CRP and homocysteine do not go back to normal
levels with resolution of DKA/HHS
Causes of DKA/HHS








New diagnosis of Diabetes
Infection: Pneumonia, Gastroenteritis, UTI
Pancreatitis
Acute MI/ACS
Stroke
Trauma
Alcohol/Drugs/Medications
Missed Insulin/Compliance
In between type 1
and type 2
• Unprovoked ketosis
• Absent islet cell antibodies
• Frequent evolution to Insulin independence over
time
Flatbush or ketosis prone
diabetes
• ADA classification: type 1a (Ab+) and type 1b (Ab-)
• AβClassification based on presence of antibodies
(GAD65 autoantibody) and cell reserve (C peptide
levels)
Symptoms of DKA


Develops rapidly
Earliest symptoms are due hyperglycemia



Polyuria, Polydipsia, Weight loss
Neurologic symptoms
Abdominal pain, nausea, vomiting
Up to 50% of DKA
 Associated with degree of acidosis
 ?Delayed gastric emptying/ileus

Physical Exam in DKA

Signs of dehydration





Tachycardia, hypotension
Neurologic exam
“Acetone breath”
Kussmaul Respirations
Fever is rare, even with infection
Evaluation

Laboratory








Glucose
Electrolytes
CBC
Serum Ketones
Plasma Osmolality
ABG (venous pH 0.03
lower)
Urinalysis
?Amylase/Lipase
•
Other
o
o
o
o
o
Electrocardiogram
Chest X-Ray
Blood Culture
Urine Culture
Sputum Culture
Labs in DKA: ABG and
ketones
Labs in DKA: Glucose


Usually between 300-500 mg/dl
“Euglycemic DKA”
Nutritional deficiency
 Pregnancy
 Prior use of insulin en route to the E.R.

Labs in DKA: Sodium



Variable sodium levels
Direct effect of hyperglycemia leads to
hyponatremia (↓1meq/L for every 62 mg/dl rise in
BS) due to fluid shift from intracellular to extracellular
space
Need to compute for corrected sodium



Corrected Na = serum sodium +1.6 for ever 100 mg/dl above 100
Secondary effect of osmotic diuresis which causes
loss of free water→hypernatremia
Most are mildly hyponatremic
Labs in DKA: Potassium

Overall potassium deficit
Renal loss with osmotic diuresis & ketone excretion
 GI loss


However, on initial evaluation, K level is usually
normal or elevated
Hyperosmolarity
 Insulin deficiency
 ?Acidemia


Take great care in monitoring/repleting K for fear of
arrythmias
Labs in DKA: Other

Phosphate


Amylase/Lipase



Usually body depleted, but initial levels may be normal or high
May be elevated, even without pancreatitis
Elevated WBC
Hyperlipidemia

Elevated TC & Trigs
Formulas
•Corrected Na = serum sodium +1.6 for ever 100 mg/dl
above 100
•Fluid deficit = (Corrected Na- Goal of 140/ 140) x 0.6 x
kg BW
•Anion Gap = Na – (Cl+HC03)
•Osmolarity = 2Na +glucose in mg/dl/18
Anion Gap





AG= Na – (Cl + HCO3)
Normal <12; DKA >20
Accumulation of BHB & AA
Test in serum & urine
Nitroprusside reaction converts AA to acetone and
(does not detect BHB)
Test may be negative test if most of the anions are BHB
 Adding Hydrogen Peroxide to urine the urine converts BHB to AA & allows
NP reaction

Anion Gap
High Anion Gap
•Methanol
•Uremia and RF
•Diabetes and other
ketotic states
•Paraldehyde
•INH
•Ethylene glycol
•Salicylate
add lactic acidosis
Normal Anion Gap
•ureteroenterostomies
•Sulfamylon
•Enteric fistulas
•Diarrhea
•Cholestyramine
•Aldactone, acidifying
agents,actazolamide
•RTA
add HAL
Treatment of DKA





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Initial Evaluation: ABCs; Exam; Labs; Causes
Close Monitoring
Fluid Replacement
Insulin Therapy
Electrolyte Replacement
Resolution & Conversion to home therapies
Monitoring




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ICU Status
Blood sugar monitoring q1 hr
Electrolytes ,venous pH q2-4 hrs
Ketones q 6H
Close evaluation of vitals & neuro status
Consider use of flowsheet
DKA/HHS flowsheet for the documentation of clinical parameters, fluid and electrolytes,
laboratory values, insulin therapy, and urinary output.
et al. Dia Care 2003;26:s109-s117
Copyright © 2011 American Diabetes Association, Inc.
Fluid Replacement




Mainstay of initial therapy
Expand the intravascular volume & improve renal
blood flow
Ave fluid loss for DKA: 3-6 Liters (8-10 in HHS)
Isotonic saline




Rapidly infuse volume without acute lowering of plasma
osmolarity
Switch to ½ NS in subacute phase if Na normal or high
15-20 ml/kg initially then decrease to 5-10ml/kg/hr
Fluids alone my initially decrease BG by 35-70
ER doc’s recommendation: Hardern and Quinn
Emerg Med J 2003; 20:210-13
• 500 ml x 4 hours then 250 x 4 hours
• Make sure lines are in
• Insert NGT and Urine catheter
Insulin Therapy

Role of Insulin




Lower serum glucose (mainly by decreasing liver
production)
Reduce ketogenesis in liver by reducing lipolysis and
glucagon secretion
Increase ketone utilization
Insulin IV bolus and continuous drip is standard of
care

Some studies have looked at frequent, rapid-acting insulin,
but not enough data to support use except in mild DKA
cases
Insulin Therapy

Check Potassium first!
If K <3.3, delay insulin until begin K repletion
 May drive insulin into the cells and lead to life-threatening hypokalemia




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IV bolus of regular insulin: 0.1 U/Kg
Continuous infusion, start at 0.1 U/Kg/hr
Goal is to decrease glucose by 50-70 mg/dl per
hour; will require further titration of drip
Higher rates in the young compared to the old
Higher rates in those with Type 2 diabetes
Insulin Therapy


Once BS < 200 (<300 in HHS) start dextrose (usually
D5 ½ NS) and decrease insulin drip rate to 1/5 of
previous
Addition of dextrose to IVF
Avoid hypoglycemia
 Continue insulin drip while awaiting resolution of ketoacidosis
 Continue nutrition while patient NPO


Need to overlap IV drip with SQ insulin to avoid
going back into ketosis
Comparison of the effects of iv, sc, and im low-dose insulin regimens on changes of plasma
glucose and total ketone bodies in patients with DKA. Reprinted from Fisher et al.
Kitabchi A E et al. JCEM 2008;93:1541-1552
©2008 by Endocrine Society
SQ Aspart vs. I.V.Regular
insulin
• BOLUS 0.3 u/kg/hour then
• Aspart SQ 0.1 u/hr until glucose is less than 250
mg/dl then decrease dose to 0.05 u/hr till DKA
resolves
OR
Aspart SQ 0.2 u/2hr until glucose is less than
250 mg/dl then decrease dose to 0.05 u/hr till
DKA resolves
Aspart vs. Regular insulin
Bicarbonate and pH
A: Serum insulin levels before and after subcutaneous injection (at 0 min) of insulin aspart (•)
or insulin lispro (○) in seven patients with type 1 diabetes.
Homko C et al. Dia Care 2003;26:2027-2031
Copyright © 2011 American Diabetes Association, Inc.
Plasma levels of FFA (A) and total ketone bodies (β-hydroxybutyrate plus aceto-acetate, B)
before and after subcutaneous injection (at 0 min) of either insulin aspart (•) or insulin lispro
(○) in seven patients with type 1 diabetes.
Homko C et al. Dia Care 2003;26:2027-2031
Copyright © 2011 American Diabetes Association, Inc.
Changes in metabolic profile in patients with DKA treated with intravenous glulisine (○) and
regular insulin (●).
Umpierrez G E et al. Dia Care 2009;32:1164-1169
Copyright © 2011 American Diabetes Association, Inc.
IV Glilusine vs. IV
Regular insulin
Potassium Replacement


If initial K high, should not need more therapy than
insulin, which will drive K into the cells
To prevent hypokalemia, add KCl to IVF if K<5.3
If K normal, 20-30 meq/liter of IVF is adequate
 If K low, may need more aggressive rx
 If using 40 meq KCl in saline, may use ½ NS as this will create isotonic
solution
 NS = 154 cation equiv
 ½ NS = 77; ½ NS + 40 meq KCl = 117 (~3/4 NS)

Effects of acidosis in
experimental studies
• Initially acidosis from ketones, lactic acidosis and
renal dysfunction
• Subsequently, Hyperchloremic acidosis due to
preferential excretion of ketones over chloride and
from saline administration
• Impairs myocardial contractility
• Reduces cardiac output
• Affect oxyhemoglobin dissociation and tissue
oxygen delivery
• Inhibit intracellular enzymes
• Alter cellular metabolism
Marked heterogeneity and
NO clear evidence
Parameter
Hospitalization
Benefit
No difference
2
Harm
1
Mortality
Resolution of Acidosis/ketosis
8
Insulin sensitivity/ glucose
Potassium balance
7
11
3
5
Tissue oxygenation
1
CSF acidosis
2
Cerebral edema
1
Neurological outcomes
3
Hemodynamic outcomes
1
1
2
Bicarbonate Therapy

Concerns with use:
Rapid rise in pH will shift the O2 dissociaiton curve to the left. This
results in decrease tissue oxygenation. The rise in pCO2 results in
an increase in lactate and acidosis
 The rise in lactate may lead to fall in cerebral pH contributing to
edema


Consider use with:
pH <7.0, especially if decreased cardiac function
 Life-threatening hyperkalemia



Dose: 50-100 meq NaHCO3 (1-2 amps) over 2 hours
Does not apply to HHS
Phosphate Therapy


Most patients phosphate depleted
Usually level will fall with initial therapy





Driven into the cells with resolving acidosis
Improved renal perfusion→excretion
Most patients do not have symptoms related to
hypophosphatemia
Routine use not necessary
If evidence of cardiac dysfunction, hemolytic
anemia, or respiratory depression in pts with phos
<1.0 mg/dl

20-30 meq/L of Potassium Phosphate, added to IVF
Resolution
DKA
•Blood glucose <200 mg/dl
•PLUS 2 0f the following:
o Bicarbonate ≥15 mEq/ml
o Venous ph 7.3
o Anion gap ≤12 mEq/l
HHS
•Normal osmolality
•Normal mental status
Complications

Related to underlying illness

Cerebral edema

Decreased arousal, Lethargy after initial improvement, headache,
vomiting, relative bradycardia and hypertension, seizures,
incontinence,pupillary changes 4-12 hrs after tx

0.5-1% of cases, mostly in children, case rate constant across 6 decades

Mortality 20-25%
Cerebral edema

Theories:
 Hypoxia induced damage to blood brain
barrier

Saline bolus increases capillary hydrostatic
pressure resulting in interstitial edema

Fluid shift along the osmolar gradient
secondary to overzealous hydration/insulin use

Activation of the Na-H exchanger by insulin
Cerebral edema

Reduce risk by
 Slow rehydration in 48 hours, gradual
replacement of Na & H2O deficits in
hyperosmolar patients & adding dextrose
to IV solution once appropriate,
 supplemental oxygen
Cerebral edema

Treatment
 3% Nacl 5-10 ml/kg or

mannitol 0.25-1 g/kg over 20 mins

I case report:octreotide at 3.5 ug/kg/hr
(suppresses IGF 1 and GH levels leading to
lower glucose values)
Prevention

Improved access to medical care

Education
When to contact doctor if illness occurs
 Increased use of short-acting insulin during illness
 Continued use of insulin & BS monitoring when illness prevents eating
 Continued nutrition during times of illness
