Transcript Diabetic Ketoacidosis Management

Diabetic Ketoacidosis
Management
Heidi Chamberlain Shea, MD
Endocrine Associates of Dallas
Goals of Discussion
•
•
•
•
•
Pathophysiology of DKA
Biochemical criteria for DKA
Treatment of DKA
Prevention of DKA
Hyperosmolar Nonketoic Syndrome
Epidemiology
• Annual incidence in
U.S.
– 5-8 per 1000 diabetic
subjects
• 2.8% of all diabetic
admissions are due to
DKA
• Overall mortality rate
ranges from 2-10%
– Higher is older
patients
DKA
Precipitating Factors
• Failure to take insulin
• Failure to increase insulin
– Illness/Infection
• Pneumonia
• MI
• Stroke
– Acute stress
• Trauma
• Emotional
• Medical Stress
– Counterregulatory
hormones
• Oppose insulin
• Stimulate glucagon
release
• Hypovolmemia
– Increases glucagon and
catecholamines
• Decreased renal blood
flow
• Decreases glucagon
degradation by the kidney
Diabetic Ketoacidosis
Due to:
Severe insulin deficiency
Excess counterregulatory hormones
Glucagon
Epinephrine
Cortisol
Growth hormone
Role of Insulin
• Required for transport of glucose into
– Muscle
– Adipose
– Liver
• Inhibits lipolysis
• Absence of insulin
– Glucose accumulates in the blood
– Liver
• Uses amino acids for gluconeogenesis
• Converts fatty acids into ketone bodies
– Acetone, Acetoacetate, β-hydroxybutyrate
– Increased counterregulatory hormones
Counterregulatory Hormones - DKA
Epinephrine
Increases
insulin
resistance
Activates
glycogenolysis
and
gluconeogenesis
Activates
lipolysis
Inhibits insulin
secretion
X
X
X
X
X
X
Glucagon
X
Cortisol
X
Growth
Hormone
X
X
Insulin Deficiency
Glucose uptake
Lipolysis
Proteolysis
Glycerol
Free Fatty Acids
Amino Acids
Hyperglycemia
Osmotic diuresis
Gluconeogenesis
Glycogenolysis
Ketogenesis
Dehydration
Acidosis
Signs and Symptoms of DKA
• Polyuria, polydipsia
– Enuresis
• Dehydration
– Tachycardia
– Orthostasis
• Abdominal pain
– Nausea
– Vomiting
• Fruity breath
– Acetone
• Kussmaul breathing
• Mental status
changes
– Combative
– Drunk
– Coma
Lab Findings
• Hyperglycemia
• Anion gap acidosis
– (Na + K) – (Cl + Bicarb) >12
– Bicarbonate <15 mEq/L
– pH <7.3
• Urine ketones and
serum ketones
• Hyperosmolarity
Differential Diagnosis
Anion Gap Acidosis
•
•
•
•
•
Alcoholic ketoacidosis
Lactic acidosis
Renal failure
Ethylene glycol or methyl alcohol poisoning
Starvation in late pregnancy or lactation
(rare)
Atypical Presentations
• DKA can be present with BS <300
– Impaired gluconeogenesis
•
•
•
•
Liver disease
Acute alcohol ingestion
Prolonged fasting
Insulin-independent glucose is high (pregnancy)
– Chronic poor control but taking insulin
• Bedside urine ketones false negatives
– Measure acetoacetate not β-hydroxybutyrate
– Send blood to lab
Treatment of DKA
• Initial hospital
management
– Replace fluid and
electrolytes
– IV Insulin therapy
– Glucose administration
– Watch for complications
– Disconnect insulin pump
• Once resolved
– Convert to home insulin
regimen
– Prevent recurrence
Treatment of DKA
Fluids and Electrolytes
• Fluid replacement
– Restores perfusion of the tissues
• Lowers counterregulatory hormones
– Average fluid deficit 3-5 liters
• Initial resuscitation
– 1-2 liters of normal saline over the first 2 hours
– Slower rates of 500cc/hr x 4 hrs or 250 cc/hr x 4
hours
• When fluid overload is a concern
• If hypernatremia develops ½ NS can be used
Treatment of DKA
Fluids and Electrolytes
• Hyperkalemia initially present
– Resolves quickly with insulin drip
– Once urine output is present and K<5.0, add 20-40
meq KCL per liter.
• Normo/Hypokalemia
– Malnourished individuals (alcoholics)
– Start K replacement and have K > 3.0 prior to start of
insulin
– Remember to check magnesium
• Phosphate deficit
– May want to use Kphos
• Bicarbonate not given unless pH <7 or
bicarbonate <5 mmol/L
Treatment of DKA
Insulin Therapy
• IV bolus of 0.1-0.2 units/kg (~ 10 units)
regular insulin
• Follow with hourly regular insulin infusion
• Glucose levels
– Decrease 75-100 mg/dl hour
– Minimize rapid fluid shifts
• Continue IV insulin until urine is free of
ketones
Treatment of DKA
Glucose Administration
• Supplemental glucose
– Hypoglycemia occurs
• Insulin has restored glucose uptake
• Suppressed glucagon
– Prevents rapid decline in plasma osmolality
• Rapid decrease in insulin could lead to cerebral
edema
• Glucose decreases before ketone levels
decrease
• Start glucose when plasma glucose
<300 mg/dl
Insulin-Glucose Infusion for DKA
Blood glucose
<70
70-100
101-150
151-200
201-250
251-300
301-350
351-400
401-450
451-500
>500
Insulin Infusion
0.5 units/hr
1.0
2.0
3.0
4.0
6.0
8.0
10.0
12.0
15.0
20.0
D5W Infusion
150 cc/hr
125
100
100
75
50
0
0
0
0
0
Complications of DKA
• Infection
– Precipitates DKA
– Fever
– Leukocytosis can be secondary
to acidosis
• Shock
– If not improving with fluids
r/o MI
• Vascular thrombosis
– Severe dehydration
– Cerebral vessels
– Occurs hours to days after
DKA
• Pulmonary Edema
– Result of aggressive fluid
resuscitation
• Cerebral Edema
–
–
–
–
First 24 hours
Mental status changes
Tx: Mannitol
May require intubation with
hyperventilation
Once DKA Resolved
Treatment
• Most patients require 0.5-0.6 units/kg/day
• Pubertal or highly insulin resistant patients
– 0.8-1.0 units/kg/day
• Long acting insulin
– 1/2-2/3 daily requirement
– NPH, Levemir or Lantus
• Short acting insulin
– 1/3-1/2 given at meals
– Regular, Humalog, Novolog or Apidra
Once DKA Resolved
Treatment
• Give SQ insulin at least 2 hours prior to stopping
insulin infusion.
• Lantus or Levemir
– Steady state at 2-4 hrs
• Short acting analogs for meal times
• If transitioning to the pump
– Restart the pump and after 30 minutes stop insulin
infusion
• May still be more insulin resistant so will need
more than usual dose
• Check blood sugars in 2 hrs
– Offer supplemental
I
Insulin Types and Action
INSULIN
TYPE
ONSET OF
ACTION
PEAK
EFFECT
DURATION
OF ACTION
Humalog
Novolog
Apidra
15 MIN
1 ½ HOURS
3 HOURS
REGULAR
30 MIN
2-3 HOURS
4-6 HOURS
NPH
2-3 HOURS
6-8 HOURS
12-16 HOURS
LENTE
3-4 HOURS
8-12 HOURS
12-18 HOURS
Glargine
Detemir
1-2 hrs
24 hrs
Prevention of DKA
Sick Day Rules
• Never omit insulin
– Cut long acting in half
• Prevent dehydration and
hypoglycemia
• Monitor blood sugars
frequently
• Monitor for ketosis
• Provide supplemental fast
acting insulin
• Treat underlying triggers
• Maintain contact with
medical team
Preventing DKA
•
Education
– Sick days or NPO
•
•
•
•
Do not stop insulin but adjust
Continue basal insulin
NPH insulin- decrease by 30-50%
Use short acting
– Q2-3 hrs with Novolog, Humalog and Apidra
– Q4 hrs with regular insulin
– Hyperglycemia
• If > 300 mg/dl, then check urine ketones
• If ketones positive
– Increase fluids
– Take supplemental insulin Q2 hrs
– Insulin temperature sensitive
•
•
•
•
•
< 77 degrees
Teenagers, homeless, pen and pump users
Do not store insulin in the car
Traveling and summer outdoor activities
May need to replace more frequently
Pump patients
• If blood sugars are
increasing (>200 mg/dl)
– Bolus
– Check 2 hrs later, if
climbing
– Give SQ correction
– Change site
– Make sure pump is working
– Change insulin
• Pump patients need long
acting back up at home
and when traveling
Pump patients
• If in DKA
– Disconnect the pump
• Transitioning back to
pump
– Start pump with basal
x 2 hrs, then stop
insulin drip
– Check blood sugars
every 2 hrs to make
sure they are in range
Clinical Trials
• Immune modulating studies
– www.jdrf.org
– www.ClinicalTrials.gov
• Anti CD3- monoclonal AB
– Phase 3 trials
– Newly diagnosed Type 1 Diabetes
• Call Research Institute of Dallas 214-363-5535
• Immune modulating vaccines
• Stem cell and pancreas transplants
Goals of Discussion
•
•
•
•
•
Pathophysiology of DKA
Biochemical criteria for DKA
Treatment of DKA
Prevention of DKA
Hyperosmolar Nonketoic Syndrome
Hyperosmolar Nonketotic
Syndrome
• Extreme hyperglycemia and dehydration
– Unable to excrete glucose as quickly as it
enters the extracellular space
– Maximum hepatic glucose output results in a
plateau of plasma glucose no higher than
300-500 mg/dl
– When sum of glucose excretion plus
metabolism is less than the rate which
glucose enters extracellular space.
Hyperosmolar Nonketotic
Syndrome
• Extreme hyperglycemia and hyperosmolarity
• High mortality (12-46%)
• At risk
– Older patients with intercurrent illness
– Impaired ability to ingest fluids
• Urine volume falls
– Decreased glucose excretion
• Elevated glucose causes CNS dysfunction and fluid
intake impaired
• No ketones
– Some insulin may be present
– Extreme hyperglycemia inhibits lipolysis
Hyperosmolar Nonketotic Syndrome
Presentation
•
•
•
•
Extreme dehydration
Supine or orthostatic hypotension
Confusion
coma
Neurological findings
– Seizures
– Transient hemiparesis
– Hyperreflexia
– Generalized areflexia
Hyperosmolar Nonketotic Syndrome
Presentation
• Glucose >600 mg/dl
• Sodium
– Normal, elevated or low
• Potassium
– Normal or elevated
• Bicarbonate >15 mEq/L
• Osmolality >320 mOsm/L
Hyperosmolar Nonketotic Syndrome
Treatment
• Fluid repletion
– NS 2-3 liters rapidly
– Total deficit = 10 liters
• Replete ½ in first 6 hours
• Insulin
– Make sure perfusion is adequate
– Insulin drip 0.1U/kg/hr
• Treat underlying precipitating illness
Clinical Errors
• Fluid shift and shock
– Giving insulin without sufficient fluids
– Using hypertonic glucose solutions
• Hyperkalemia
– Premature potassium administration before insulin has begun to
act
• Hypokalemia
– Failure to administer potassium once levels falling
• Recurrent ketoacidosis
– Premature discontinuation of insulin and fluids
when ketones still present
• Hypoglycemia
– Insufficient glucose administration
Conclusion
• Successful management
requires
– Judicious use of fluids
• Establish good perfusion
– Insulin drip
• Steady decline
• Complete resolution of ketosis
– Electrolyte replacement
– Frequent neurological
evaluations
– High suspicion for complications
• Determine etiology to avoid
recurrent episodes