Full text


Janet Lin, MD, MPH 1. Diabetes Mellitus (DM)

a. Historical Perspective

i. First described in Egypt 3000 years ago

ii. Named diabetes (for siphon) mellitus (for honey) by Celsus at the time of Christ

iii. In 1924, the discovery of insulin by Banting and Best led to increased lifespan and reduced complications.

b. Incidence

i. National Health Interview Survey indicates that 1.3 million new cases of diabetes are diagnosed per year*

1. Estimated true prevalence (diagnosed and undiagnosed) is 18.2 million. That is 6.3 % of the U.S. population.*

2. Higher incidence in women and non-Hispanic blacks.* ii. Estimated annual cost: $132 billion.*

iii. Geographic variation

1. Uncommon in Israel, southern Europe 2. Higher in central Europe

3. Even higher in Scandinavia and United States *CDC National Diabetes Fact Sheet, 2003 c. Classification of Diabetes Mellitus

i. Type I

1. Insulin-dependent 2. Ketosis-prone

3. 97% of children with DM have Type 1 ii. Type II

1. Non-insulin dependent 2. Ketosis-resistant 3. Usually maturity onset

4. Relative, rather than absolute, insulin deficiency 5. Roughly half due to obesity

2. Diabetic Ketoacidosis (DKA)

a. Definition: Diabetic ketoacidosis (DKA) is a state of endocrinologic

imbalance resulting from insulin deficiency and counter-regulatory hormonal excess, characterized by hyperglycemia (blood glucose in excess of 300


mg/dL), ketonemia (serum ketones positive at a dilution of 1:2 with the sodium nitroprusside test), and acidosis ( pH less than 7.30 or bicarbonate less than 15 mEq/L).

b. Incidence

i. 46 episodes per 10,000 diabetics

ii. 102,000 discharges in 2002 (in 1980 there were 62,000)

iii. African-Americans outnumber whites, though gap is decreasing iv. Initial presentation of DM is DKA in approximately 10% of cases

(20-30% per Kriesberg)

v. Highest incidence in 0-19 age group

c. Mortality (1871 deaths in 2001, has remained the same since ~ 1980) i. Death rates are highest in the young and the extremely old

1. In 2001, the DKA death rate among people aged 45 years and younger (25.2 per 100,000 diabetic population) was about three times that of those aged 65-74 years (8.0 per 100,000 diabetic population)

ii. Causes in children

1. Metabolic derangement of DKA 2. Intercurrent illness, particularly sepsis 3. Abnormalities induced by treatment

a. Cerebral edema b. Overhydration

c. Electrolyte disturbances d. Hypoglycemia

e. Alkalosis iii. Additional causes in adults

1. Myocardial infarction

2. Thromboembolic phenomena d. Factors predisposing to the development of DKA

i. Lack of adequate knowledge of the disease on the part of the patient and family (2 out of 3 cases)

ii. Psychological problems

1. Withholding insulin for secondary gain 2. Suicidal gestures/attempts

iii. Lack of medications/supplies due to financial difficulties iv. Intercurrent illness (80% have identifiable precursor)

1. Infection (30-40%) a. Respiratory b. Urinary c. Sinuses d. Otitis e. Pilonidal/perirectal abscesses f. Deep planter abscesses


g. Mucormycosis 2. Vomiting

3. Myocardial infarction (5-7%) a. Especially in the elderly

b. May not present with chest pain 4. Cerebrovascular accident (CVA) 5. Pregnancy

a. Increased insulin requirement in second trimester v. Trauma

vi. Exercise

vii. Excess insulin (Somogyi effect)

viii. Malfunction of continuous insulin pumps ix. Medications

1. Terbutaline 2. Pentamidine e. Pathophysiology

i. Insulin deficiency (relative or absolute) ii. Prevents glucose from entering cells

iii. Precipitants (stress) and intracellular starvation cause release of counter-regulatory hormones (CRH) – Unger, 1971

1. Catecholamines: secondary effect produces lypolysis and glycogenolysis

2. Glucagon: principle effect on HGP and ketogenesis 3. Cortisol: distant effect: gluconeogenesis from muscle 4. Growth hormone: little effect

iv. CRH causes:

1. Increased gluconeogenesis - breakdown of proteins and subsequent conversion of amino acids into glucose

2. Increased glycogenolysis - breakdown of liver glycogen into glucose

3. Increased lipolysis - breakdown of adipose tissue to provide non-esterified fatty acids (NEFA)

v. ii. and iv. above lead to hyperglycemia

1. Only moderate hyperglycemia if intact renal function, intact thirst mechanism (15% <350 mg/dL)

2. Severe hyperglycemia (>600 mg/dL): develops in presence of vomiting, obtundation, inability to communicate, prisoners 3. Pregnant women have only a moderate increase due to volume

expansion, increased GFR, fetal use of glucose even without insulin

4. Alcoholics have modest increases in blood sugar due to decreased glycogenolysis and gluconeogenesis

vi. Hyperglycemia produces hyperosmolarity, glucosuria

vii. Glucosuria causes an osmotic diuresis and subsequent dehydration viii. Ketoacids release hydrogen ions producing acidosis


ix. Acidosis and dehydration combine to produce electrolyte imbalance x. Dehydration is worsened by increased insensible fluid loss

1. Diaphoresis 2. Tachypnea

xi. Uncorrected dehydration may lead to shock

xii. Shock will produce lactic acidosis and worsen the pre-existing acidotic state

xiii. Dehydration or shock will lead to decreased glomerular filtration which will worsen the hyperglycemia

xiv. Acute tubular necrosis may result f. Clinical presentation

i. DKA usually develops slowly over a period of weeks ii. Early symptoms

1. Polyuria

2. Polydipsia {due to hyperglycemia 3. Polyphagia

4. Visual disturbances

5. Weight loss {due to muscle breakdown 6. Weakness and dehydration iii. Later symptoms

1. Anorexia, nausea, vomiting {due to ketonemia 2. “Fruity” acetone breath

3. Abdominal pain

4. Kussmaul respirations {due to acidosis (deep, regular, sighing)

5. Altered level of consciousness {due to hyperosmolarity a. Alert patients have osm <330 mOSM/kg

b. Alert (20%) to coma (10%) 6. Gastric stasis, ileus

7. Muscle cramps {due to hypokalemia 8. Cardiac arrhythmias

iv. Mild forms may present with vague symptomatology

v. Hyperpyrexia is rarely seen, even in the presence of infection vi. The most severe cases are usually in infants or mentally retarded

children who can’t communicate their feeling of thirst vii. Clinical symptoms/signs do not always parallel the degree of

biochemical abnormality viii. Assessment of dehydration


1. Compensatory mechanisms (tachycardia, vasoconstriction) may mask a significant degree of dehydration until sudden vascular collapse

2. Assume 10% dehydration

3. Weight change is helpful if previous weight is known

4. Furrowed tongue is a good indication of severe dehydration (on the order of 30%)

ix. PEARL: the dehydrated patient who is still voiding has DKA until proven otherwise

g. Differential diagnosis i. Hypoglycemia ii. Meningitis iii. Acute abdomen

iv. Gastroenteritis – the most common ED misdiagnosis v. Respiratory infection

vi. Toxic ingestions, especially salicylates vii. CVA

viii. Brainstem hemorrhage ix. Uremia

x. Alcoholic ketoacidosis xi. Starvation ketosis h. Laboratory evaluation

i. Immediate – determinations that will guide immediate therapy 1. Dipstick determination of blood glucose with a paper strip

technique evaluated by monitor

2. Urine glucose and acetone (using Clinitest and Acetest tablets or Chemstrips bG)

a. If moderate to large acetone, order serum acetone 3. Blood gas

a. If pure metabolic acidosis, last two numbers of the pH=pCO2

b. Mixed acid-base abnormalities

i. Respiratory alkalosis with hypoxemia: consider pneumonia or ARDS

ii. Respiratory alkalosis without hypoxemia: consider sepsis

iii. Metabolic alkalosis: consider vomiting,

diuretics, alkali ingestion, Cushing’s syndrome 4. Electrocardiogram (EKG)

ii. Delayed – specimens for these test are drawn immediately but results may not be available for up to an hour

1. Complete blood count (CBC)

a. WBC is usually 15-20,000 due to demargination and dehydration even in the absence of infection


i. WBC >30,000 suggests infection

ii. Bands >10 is 100% sensitive and 80% specific for infection

b. Hemoglobin and hematocrit are elevated due to dehydration

2. Electrolytes a. Sodium

i. Losses in DKA average 6 mEq/kg due to osmotic diuresis and excretion as cation with ketoacids.

ii. Sodium level will be spuriously low due to hyperglycemia.

1. True value: add 1.6 to the serum sodium for every 100mg/dL of blood glucose over 100mg.dL.

2. If the corrected Na is elevated, a large free water deficit is indicated and the patient is at risk for developing hypotension and shock.

iii. Hyperliponemia also causes a spuriously low result due to the increase in the volume of the specimen from the lipids.

b. Potassium

i. Losses in DKA average 5 mEq/kg due to excretion with ketoacids

ii. Initial serum level will be normal or high due to extracellular shift as a compensatory mechanism in acidosis

iii. Falls precipitously with administration of fluids, insulin and especially bicarbonate

c. Chloride

i. Losses in DKA average 4 mEq/kg

ii. Excessive replacement is common, leading to hyperchloremic acidosis. This results in a persistent low bicarbonate which is of no

concern as long as the anion gap is normalizing. d. Anion gap (AG)

i. AG = Na – [Cl + HCO3]

ii. Normal = 6-12 due to albumin, sulfates, phosphates, and some lactate

iii. Reflects excess ketoacids in DKA iv. Good parameter to follow

3. Blood urea nitrogen and creatinine a. Elevated by dehydration

b. Creatinine level may be spuriously elevated to 2-3 mg/dL by the presence of ketones


4. Blood glucose 5. Magnesium

a. Total body stores are always depleted

b. Changes in serum levels parallel those of potassium (initially normal-high, then fall with therapy) 6. Phosphorus

a. Total body losses in DKA average 3 mEq/kg b. Levels are variable at presentation but drop during


c. Hypophosphatemia is usually asymptomatic but theoretically could cause decreased 2,3–

diphophoglycerate (2,3–DPG) which would cause the oxyhemoglobin dissociation curve to shift to the left, making oxygen less available to the tissues.

d. Administration of some of the potassium replacement as potassium phosphate instead of potassium chloride may help prevent excessive chloride administration and the resultant hyperchloremic acidosis.

e. If given, monitor for hypocalcemia

7. Calcium (excessive phosphate administration can lead to hypocalcemia)

8. Osmolality (measured or calculated)

a. Serum osmolality = 2Na + glucose/18 + BUN/3 b. Observation of osmolality is essential during treatment

to prevent rapid falls which may be responsible for the development of cerebral edema

9. Serum acetone

a. The ketone bodies, acetoacetate and

B-hydroxybutyrate, exist in equilibrium with each other and the presence of acidosis favors the formation of B-hydroxybutyrate

b. The nitroprusside reaction, which is commonly used to measure serum and urine ketones, will pick up only acetoacetate and acetone. Therefore, in severe acidosis, measured ketones may be spuriously absent or low. Likewise, measured ketones may increase as treatment takes effect.

10. Serum amylase

a. If measured, serum amylase is usually high b. Fractionation shows this to be the salivary type 11. Urinalysis

a. Elevated glucose/ketones (glucosuria usually present when blood glucose exceeds 300)

b. Proteinuria {due to

c. Hyaline casts dehydration d. Microscopic evidence of infection


12. Evaluation for infection as indicated a. Chest x-ray b. Blood cultures c. Urine culture d. Lumbar puncture i. Management


1. Lowers blood glucose by as much as 18% 2. Normalizes pH

3. Children

a. If in shock, given 20mL/kg normal saline (NS) bolus. May repeat if needed

b. If not in shock, give 20mL/kg NS over the first hour c. Assume 10% dehydration unless clinical signs indicate

more severe dehydration

d. Calculate the fluid deficit, add in the maintenance requirement, and replace over 36 hours (1/2 in first 12 hours and 1/2 over the next 24 hours)

e. Change to 1/2 NS after the first hour 4. Adults

a. Fluid deficit usually 3-6 liters

b. Give first liter as normal saline (NS) over 30 minutes c. Give second liter as NS over 1-2 hours

d. Then 1/2 NS at 300-500mL/hr, guided by urine output (1-2 ml/kg/hr)

e. Caution should be exercised with older patients and those with cardiovascular disease. Hemodynamic monitoring should be considered.

ii. Electrolytes 1. Potassium

a. If T-waves on EKG are peaked, hold the potassium b. If T-waves are normal, flat, of inverted and the patient

has urinated, give 20-40 mEq potassium (half KCl and half K3PO4) in the first liter

c. Monitor levels hourly and continue potassium replacement unless serum level is elevated.

i. K < 3: use 40 mEq/hr ii. K < 4: use 30 mEq/hr iii. K < 5: use 20 mEq/hr iv. K > 5: do not use

v. Children: use 0.25-0.5 mEq/kg/hr 2. Magnesium

a. 4 grams of magnesium per liter of fluid unless serum level is elevated


iii. Initiate a flow sheet

1. Hourly lab values (or with each liter of fluid) a. Glucose

b. Electrolytes c. Osmolality d. Blood gases

e. Output: catheter only if no urine after one hour or patient is obtunded

2. Decrease frequency as patient improves 3. Heparin lock with facilitate blood draws 4. Vital signs

5. Mental status iv. Insulin

1. Route of administration

a. Intramuscular may give delayed absorption b. Subcutaneous requires high doses leading to rapid

fluctuations in blood glucose

c. Low-dose continuous intravenous infusion provides a predictable, linear decrease in blood sugar; although the slope of decline varies from patient to patient

i. Prevents hypoglycemia

ii. Makes hypokalemia less likely

iii. Adjustments are easy since half-life of IV regular insulin is 3-8 minutes

2. Goal is to reduce blood sugar by about 100mg/dL/hour 3. Dosage and administration

a. Delay use of insulin until one hour of fluid therapy is completed (hydration increases responsiveness) b. 0.1 unit/kg/hr (50 units added to 500cc of NS provides

a solution that delivers 0.1 unit/ml; therefore, the infusion is set at 0.1 unit/kg)

c. Loading dose of 0.1 unit/kg is recommended by some, though has fallen out of favor

d. If < 10% fall in 2 hours, double the dose. If >100 units/hr required, add steroids

e. Flushing the tubing and discarding the sample will prevent adherence of insulin to the tubing

f. Use a separate IV site for insulin administration

g. If the blood sugar is over 1000mg/dL, halve the dosage to 0.05 unit/kg/hr

h. When the blood sugar reaches 300mg/dL, halve the dosage to 0.05 unit/kg/hr and add glucose to the IV fluids. Continue to reduce by 0.5 unit/hour

i. Continue the IV infusion until acidosis is corrected, blood sugar is controlled and ketonemia is resolved. (Average time is 7 hours for glucose to come to <250, 8


hours for pH to reach 7.3 and 11 hours for bicarbonate to reach 15.)

j. Administer subcutaneous insulin (0.25 unit/kg) 30 minutes before stopping the IV infusion, and continue this every 4-6 hours for 24 hours.

k. Then titrate combined intermediate- and short-acting insulin therapy

v. Bicarbonate

1. Patients with mild to moderate DKA treated with fluids and insulin alone do well and have fewer complications

2. Complications of bicarbonate use

a. Shift of oxyhemoglobin dissociation curve to the left b. Hypokalemia/hypomagnesemia

c. Overcorrection alkalosis

d. Paradoxical cerebrospinal fluid acidosis (because CO2

diffuses readily and bicarbonate does not) e. Cerebral edema

3. If used, use only for severe acidosis: if pH < 7.0, give 1-2 mEq/kg over 2 hours. DO NOT PUSH! pH should not be corrected above 7.2. Not used much anymore.

vi. Complications of therapy 1. Persistent acidosis

a. Inadequate fluid replacement b. Untreated infectious process c. Insulin resistance – rare 2. Overhydration

3. Hypoglycemia 4. Hypokalemia

5. Cerebral edema (mild swelling is common, about 50%; clinically significant in 0.7% of children)

a. High mortality (>75%)

b. Onset 3-12 hours after treatment started

c. Initial improvement, then irritability, lethargy, seizures, coma

d. Immediate neurology consultation for intracranial pressure monitoring and mannitol therapy

e. Probably results from too rapid of a decrease in glucose or osmolality

f. Preventative measures

i. Use NS initially for fluid replacement, not half normal

ii. Do not bring blood sugar below 250 mg/dL initially

iii. Hold insulin during the first hour of therapy iv. Do not use loading dose


vi. Replace fluid deficit over 36 hours instead of 24 hours

j. Disposition

i. ICU mandatory

1. Age < 2 years or > 60 years 2. pH less than 7.0

3. Serious concurrent illness 4. (Blood sugar >1000)

ii. ICU advisable for first 24 hours in all moderate severe cases unless a metabolic unit experienced in handling DKA is available

iii. Outpatient management

1. An alert patient with vague symptoms, ketonuria, mild acidosis and mild dehydration can be treated as an outpatient. (Bonadio, 1988: Time 0 – pH >7.2, HCO3 >10 and Time 4 – pH >7.35

and HCO3 >20)

2. Fluids

a. Oral is tolerated b. IV NS

3. Insulin

a. Regular insulin, SQ, 10-20% of usual daily dose b. Repeat in 4 hours

4. If vomiting persists, admit k. Prevention of DKA

i. Proper daily blood and urine monitoring

1. A.M. urine for acetone is essential, even when monitoring blood sugar

a. If positive, each void should be checked

b. If acetonuria persists for 6 hours, the patient should see his/her doctor

c. Increase sugar-free fluid intake

d. Additional insulin (0.1-0.25 units/kg every 4-6 hours) ii. 24-hour diabetes hotline should be available

iii. Emotional stress requires attention 1. Psychological evaluation 2. Family counseling iv. Education of patient and family

v. Comprehensive therapeutic team vi. Prompt attention to any illness

1. Vomiting 2. Fever