Transcript Diabetes Mellitus Pediatric Critical Care Medicine Emory University Children’s Healthcare of Atlanta Goals & Objectives • Understand the action of insulin on the metabolism.

Diabetes Mellitus
Pediatric Critical Care Medicine
Emory University
Children’s Healthcare of Atlanta
Goals & Objectives
• Understand the action of insulin on the metabolism of
carbohydrates, protein & fat
• Understand the pathophysiology of IDDM & DKA
• Understand the management approach to the patient with
DKA
• Appreciate the complications that occur during treatment
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Classification
• Type I (insulin-dependent diabetes mellitus, IDDM)
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Severe lacking of insulin, dependent on exogenous insulin
DKA
Onset in childhood
?genetic disposition & is likely auto-immune-mediated
• Type II (non-insulin-dependent diabetes mellitus, NIDDM)
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Not insulin dependent, no ketosis
Older patient (>40), high incidence of obesity
Insulin resistant
No genetic disposition
Increase incidence due to prevalence of childhood obesity
IDDM: Epidemiology
• 1.9/1000 among school-age children in the US; 12-15 new
cases/100,00
• Equal male to female
• African-Americans: occurrence is 20-30% compared to
Caucasian-Americans
• Peaks age 5-7 yrs and adolescence
• Newly recognized cases: more in autumn & winter
• Increase incidence in children with congenital rubella
syndrome
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Type I DM
• 15-70% of children with Type I DM present in DKA at
disease onset
• 1/350 of type I DM will experience DKA by age 18 yo
• Risk of DKA increased by:
– Very young children
– Lower socioeconomic background
– No family history of Type I DM
• DKA:
– Most frequent cause of death in Type I DM
– One of the most common reasons for admission to PICU
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IDDM: Etiology & Pathophysiology
• Diminished insulin secretion by destruction of pancreatic
islets cells via autoimmune process
• 80-90% of newly diagnosed cases have anti-islet cell
antibodies
• More prevalent in persons with Addison’s disease,
Hashimoto’s thyroiditis, pernicious anemia
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Type I DM: Pathophysiology
• Progressive destruction of -cells progressive deficiency of
insulin  permanent low-insulin catabolic state
• Phases:
– Early: defect in peripheral glucose predominates
– Late: insulin deficiency becomes more severe
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Decreased renal blood
flow and glomerular
perfusion
Stimulates counter
regulatory hormone
release
Accelerated
production of glucose
and ketoacids
Dehydration
Increased lactic
acidosis
Type I DM: Pathophysiology
• Hyperglycemia glucosuria (renal threshold 180 g/dL) 
osmotic diruresis: polyuria, urinary losses of electrolytes,
dehydration, & compensatory polydipsia
• Hyperglycemia  hyperosmolality: cerebral obtundation
– {Serum Na+ + K+} x 2 + glucose/18 + BUN/3
• Counter-regulatory hormones (glucagon, catecholamines,
cortisol) are released
– Increased hepatic glucose production  impairing peripheral uptake
of glucose
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Type I DM: DKA
• Lipid metabolism: increase lipolysis
– Increased concentration of total lipids, cholesterone, TG, free FA
– Free FA shunted into ketone body formation; rate of
production>peripheral utilization & renal excretion  ketoacids
– Ketoacidosis  -hydroxybutyrate & acetoacetate  metabolic
acidosis
– Acetone (not contribute to the acidosis)
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Type I DM: DKA
• Electrolytes loss
– Potassium: 3-5 mEq/kg
– Phosphate: 0.5-1.5 mmol/kg
» 2,3-diphosphoglycerate: facilitates O2 release from HgB
» Deficient in DKA, may contribute to formation of lactic acidosis
– Sodium: 5-10 mEq/kg
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DKA: Presenting Features
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Polyuria
Polydipsia
Polyphagia
Nocturia
Enuresis
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Abdominal pain
Vomiting
Profound weight loss
Altered mental status
weakness
Type I DM: Clinical Manifestations
• Ketoacidosis is responsible for the initial presentation in up
to 25% of children
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Early manifestations: vomiting, polyuria, dehydration
More severe: Kussmaul respirations, acetone odor on the breath
Abdominal pain or rigidity may be present & mimic acute abdomen
Cerebral obtundation & coma ultimately ensue
• DKA exists when there is hyperglycemia (>300 mg/dL &
usually <1,000 mg/dL); ketonemia, acidosis, glucosuria &
ketonuria
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DKA: Physical Exam
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Tachycardia
Dry mucous membrane
Delayed capillary refill
Poor skin turgor
Hypotension
Kussmaul breathing
DKA: Physical Exam
• Dehydration
– Hyperosmolar: translocation of intracellular water to extracellualr
comparment
– A rough estimation of how dehydrated the patient is to facilitate
proper rehydration
– Studies have shown that clinical approximations often are poor
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DKA: Laboratory
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Blood glucose
Urinary/plasma ketones
Serum electrolytes
BUN/Cr
Osmolarity
CBC, blood cx (if infection is suspected)
Blood gas
DKA: Laboratory Findings
• Elevated blood glucose (usually <1,000)
• Low bicarbonate level
• Anion gap metabolic acidosis
– Unmeasured ketoacids
– Urine dipsticks measure acetoacetate: in DKA B-hydroxybutyrate
to acetoacetate is 10:1
– Helpful in determining if there is ketoacids in urine but not sererity
of DKA or response to treatment
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DKA: Laboratory Findings
• Sodium: low
– Osmotic flux of water into extracellular space reduces serum sodium
concentration
– Actual sodium: 1.6mEq/L per 100mg/dL rise in glucose over 100
– Hypertriglyceridemia  low sodium  pseudohyponatremia
• Potassium:
– Level varies depending on urinary loss and severity of acidosis
– Potassium moves extracellularly in exchange for hydrogen ions 
typical hyperkalemia on presentaion
– Total body stores are depleted due to urinary loss
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DKA: Laboratory Findings
• Phosphate
– Depleted in the setting of DKA
– Serum level may not accurately represent total body stores
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DKA: Management
• Goals: correction of
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Dehydration
Acidosis
Electrolytes deficits
Hyperglycemia
DKA: Management
• Fluids:
– Avoid impending shock
» Fluid replacement >4L/m2/24 hrs has been associate with cerebral
edema
– Usually necessary to help expand vascular compartment
» Fluid deficit should gradually be corrected over 36-48 hrs
– Rehydration fluids should contain at least 115-135 mEq/L of NaCl
» Start with NS and switch to ½ NS if neccessary
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DKA: Management
• Postassium:
– Total body depletion will become more prominent with correction of
acidosis
– Continuous EKG monitoring is standard of care
– 30-40 mEq/L: in either KCl or KPhos
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DKA: Management
• Phosphate:
– Total body depletion will become more prominent with correction of
acidosis
– Hypophosphatemia may cause rhabdomyolysis, hemolysis, impaired
oxygen delivery
– Calcium should be monitored during replacement
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DKA: Management
• Insulin should be initiated immediately
– Insulin drips 0.1 U/kg/hr (NO BOLUS)
– Gradual correction reducing serum glucose by 50-100 mg/dL/hr
– Serum glucose often falls after fluid bolus: increase in glomerular
filtration with increased renal perfusion
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DKA: Management
• Dextrose should be added to IVF when serum glucose <300
– Blood glucose levels often correct prior to ketoacidosis
– Should not lower insulin infusion unless: rapid correction of serum
glucose or profound hypoglycemia
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DKA: Management
• Bicarbonate is almost never administered
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Bicarb administration leads to increased cerebral acidosis:
HCO3- + H+  dissociated to CO2 and H2O
Bicarbonate passes the BBB slowly
CO2 diffuses freely  exacerbating cerebral acidosis & depression
• Indications for bicarbonate use: only in severe acidosis
leading to cardiorespiratory compromise
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DKA: Complication, Cerebral Edema
• Cerebral edema: 0.5-1% of pediatric DKA
– Mortality rate of 20%
– Responsible for 50-60% of diabetes deaths in children
– Permanent neurologic disability rate of 25%
• Typically develops within the first 24 hrs of treatment
• Etiology is still unclear
• Signs & symptoms:
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Headache
Confusion
Slurred speech
Bradycardia
Hypertension
DKA: Complication, Cerebral Edema
• Theories of cerebral edema
– Rapid decline in serum osmolality
» This leads to the recommendation of limiting the rate of fluid
administration
– Edema due to cerebral hypoperfusion or hypoxia
– Activation of ion transporters in the brain
– Direct effects of ketoacidosis and/or cytokines on endothelial
function
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DKA: Cerebral Edema, risk factors
• Younger age
• New onset
• Longer duration of
symptoms
• Lower PCO2
• Severe acidosis
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• Increase in BUN
• Use of bicarbonate
• Large volumes of
rehydration fluids
• Failure of correction of Na
with treatment
DKA: Cerebral Edema, treatment
• Lower intracranial pressure
– Mannitol or 3% saline
• Imaging to rule out other pathologies
• Hyperventilation & surgical decompression are less
successful at preventing neurologic morbidity & mortality
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DKA: Complications
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Thrombosis (esp with CVL)
Cardiac arrhythmias
Pulmonary edema
Renal failure
Pancreatitis
• Rhabdomyolysis
• Infection
– Aspiration pneumonia
– Sepsis
– Mucormycosis
Hyperglycemia Hyperosmolar
Syndrome
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Pathophysiology
• Insulin levels are sufficient to suppress lipolysis and
ketogenesis
• Insulin levels are inadequate to promote normal anabolic
function & inhibit gluconeogeneis & glycogenolysis
• Cell deprivation triggers counter-regulatory surge,
increasing glucose via enhanced hepatic glucose generation
& insulin resistance
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Pathophysiology
• Hyperglycemia  heightened inflammatory state 
exacerbating glucose dysregulation
• Osmotic diuresis  dehydration  decreased GFR 
further glucose elevation
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Pathophysiology
• Morbidity & mortality associated with acute hyperglycemia
– Vascular injury
– Thrombus formation
– Disrupts the phagocytotic & oxidative burst functions of the
immune systemt
– Disrupts BBB
– Disrupts metabolism of the CNS worsens the effects of ischemia on
brain tissue
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Pathophysiology
• Dehydration is a major component
• 15-20% volume depleted
– 5-10% in DKA
• Greater electrolyte loss due to massive osmotic diuresis
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Clinical Presentation
• Similar to DKA
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Polyuria
Polydipsia
Weight loss
Neurologic impairment
• Different from DKA
– Kussmaul breathing
– Acetone breath
– Abdominal discomfort, nausea & vomiting are less severe
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Laboratory Findings
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Glucose: >600 mg/dL
HCO3>15
Serum osmolarity >320 mOsml/L
pH>7.3 without evidence of significant ketosis
– Level of acidemia is influenced by severity of shock & starvation
• Lab values consistent with acute renal failure,
rhabodmyolysis & pancreatitis
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Treatment
• Insulin plays a secondary role
– Hyperglycemia can often be corrected via volume resuscitation
– Renal perfusion is improved, GF is enhanced
– Insulin gtt 0.1 U/kg/hr
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Complications
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Cardiac arrest
Refractory arrhythmias
Pulmonary thromboemboli
Circulatory collapse
Refractory shock
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Acute renal failure
Rhabdomyolysis
Neurologic deficits
Electrolyte disturbances
Multisystem organ failure
Treatment
• Adult mortality: 15%
• Pediatric prevalence of HHS is unknown
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DKA
DKA
DKA
HHS
Mild
Moderate
Severe
Plasma glucose
mg/dL
>250
>250
>250
>600
Arteial pH
7.25-7.3
7.0-7.24
<7.0
>7.3
Serum bicarb
mEq/L
15-18
10 to <15
<10
>18
Urine ketones
Positive
Positive
Positive
Small
Serum ketones
Positive
Positive
Positive
Small
Effective sOsmo
mOsm/kg
variable
variable
Variable
>320
Anion gap
>10
>12
>12
Variable
AMS
Alerg
Alert/drowsy
Stupor/coma
Stupor/coma
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DKA
HHS
Total water(L)
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Water (ml/kg)
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100-200
Na+ (mEq/kg)
7-10
5-13
CL- (mEq/kg)
3-5
5-15
K+ (mEq/kg)
3-5
4-6
PO42- (mmol/kg)
5-7
3-7
Mg2+ (mEq/kg)
1-2
1-2
Ca2+(mEq/kg)
1-2
1-2
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