Lack of insulin production prevents glucose uptake by muscle and allows unrestrained hepatic glucose production.

Lack of suppression of lipolysis leads to excess circulating FFAs which are converted into ketoacids (B-OH-butyrate and acetoacetate) by the liver.

This leads to acidemia which may impair vascular tone and cardiac function.

Marked hyperglycemia and ketonemia cause osmotic diuresis with loss of water and electrolytes.

Nausea, emesis Abdominal pain (2/2 delayed gastric

emptying/ileus 2/2 acidosis and lyte abnormalities and may correlate with degree of acidosis)

Polyuria/Polydipsia Lethargy Headache Anorexia

Usually develop over 24h or less in DKA; over multiple days more insidiously in HHS.

Possible precipitating events (“Is”)› Infection (UTI? PNA?)

› Insulin (incorrect dosing/noncompliance)

› Ischemia (myocardial….mesenteric)

› Initial presentation of DM.

› More uncommon causes› Med effect – meds that affect carb

metabolism› Steroids › High-dose thiazides› Atypical antipsychotics

› CVA› Pancreatitis › Cocaine use

In hospitalized pts without DKA who present with CVA, MI, or infection and glucose >250…

› Maintain high suspicion for DKA – check RFP for AG and serum/urine ketones.

ABCs Mental status Evidence of intercurrent illness

(infection, MI, CVA, pancreatitis) Abdominal exam – TTP, hypoactive BS Volume status

› Skin turgor› Mucosa› Flat neck veins› Orthostatic hypotension

RFP – for lytes, glc, CALCULATE AG CBC UA/ketones Plasma osmolality Serum ketones if urine ketones are

present (B-OH-Butyrate, Acetone, Acetaoacetate)

ABG if serum HCO3 reduced ECG Consider infectious w/u(blood, urine,

sputum, CXR) HbA1C may be useful

DKA HHS

Mild Mod Severe

Plasma Glc >250 >250 >250 >600

Arterial pH 7.25-7.30 7.0-7.24 <7.0 >7.30

HCO3 15-18 10-<15 <10 >18

Urine ketones

+ + + Small

Serum osm Variable Variable Variable >320

Anion Gap >10 >12 >12 Variable

DKA Lactic Acidosis

Uremia

ETOH Keto-acidosis

ASA Intox

MeOH/Ethy Glycol Intox

pH Low Low Mild Low

? ? Low

Plasma Glc High Normal Normal

Low/Nl Nl/Low Nl

Glycosuria High Negative Neg Neg Neg Neg

Plasma Ketones

High Normal Normal

Sm-Mod Normal Normal

Anion Gap High High Sl High High High High

Osmolality High Normal High Normal Normal High

Uric Acid High Normal Normal

High Normal Normal

B-OH-Butyrate Acetone & Acetoacetate

Direct measurement of B-OH-Butyrate is preferable for monitoring degree of ketonemia and is available at UHCMC (not VA)

Standard ketones may become increasingly positive as conversion from B-OH-Butyrate to acetone/acetoacetate occurs

5 Step Approach to ABGs without memorizing formulas….

1. Identify alkalosis/acidosis by pH change from 7.4. (>7.4 = alkalosis. <7.4 = acidosis).

2. Determine if primary disorder is respiratory or metabolic based on direction of change of PCO2.

If pH and PCO2 change in same direction - metabolic

If pH and PCO2 change in opposite direction - respiratory

3. Check compensation to identify other primary disorders. Metabolic Acidosis - Check Resp Compensation.

PCO2 = (1.5 × [HCO3-]) + 8 ± 2

Simplified: For every 1 mEq decrease in HCO3, PCO2 should decrease by 1.2 mmHg.

Example: If HCO3 is 9...24-9 = 15. PCO2 reduction should be 15x1.2 = 18. 40-18 = 22mmHg.

Metabolic Alkalosis – Check Resp Compensation. PCO2 rises 0.7mmHg for each 1.0 mEq rise in HCO3.

Example: If HCO3 is 34...34-24 = 10. 10 x 0.7 = 7. 40+7 = 47mmHg.

Acute Respiratory Acidosis: Every 10 mmHg rise in PCO2 = 1 meq rise

in HCO3

Chronic Respiratory Acidosis: For every 10 mmHg rise in PCO2 = 3.5

mEq rise in HCO3

Acute Respiratory Alkalosis: Every 10 mmHg drop in PCO2 = 2 meq

drop in HCO3

Chronic Respiratory Alkalosis: For every 10 mmHg drop in PCO2 = 5

mEq drop in HCO3

4. If metabolic acidosis - calculate anion gap.

Na - (Cl+HCO3)

Normal gap 12 or less.

For each gram of albumin drop less than 4 add 2.5 to calculated gap to get actual gap.

Example: Calculated gap 9. Albumin 2. Add 5 to gap = 14.

5. If AGMA - calculate delta gap.

Change in gap divided by change in bicarbonate.

(AG-12) / (24-HCO3)

<1 – AGMA + NAGMA 1-2 - Pure AGMA>2 – AGMA + Metabolic Alkalosis

In DKA, initially AGMA; as treatment proceeds many will develop a subsequent NAGMA.

› Ketoacid anions are excreted in the urine with sodium which would have been used to reproduce HCO3 in the kidney loss of “potential HCO3” which is equivalent to actual bicarb loss subsequent NAGMA.

Q1H POCT Glucose until stable

RFP/Serum osmolality q2-4h with close FU of HCO3.

Consider VBG rather than frequent ABGs for pt and intern comfort – venous pH is about 0.03 units lower than ABG.

Severe Hypovolemia – NS 1000cc/h

Milder Dehydration – evaluate corrected Na (Corrected Na = Measured Na (Glc-100/100)› Hyponatremia – 250-500cc/h NS › Normal-Hypernatremia – 250-500c/h 1/2NS

When serum glc reaches 200 (or 300 in HHS) Change to D51/2NS 150-250cc/h

Usually IV route except in mild DKA.

IV: Regular insulin 0.1U/kg bolus then 0.1U/kg/h continuous infusion OR no bolus with infusion rate alone at 0.14U/kg/h

SQ: Lispro 0.3U/kg x1 then 0.2U/kg in 1hr then 0.2U/kg SQ q2h.

If serum glc doesn’t fall by 50-70 mg/dL in 1st hour double the IV or SQ dose.

K <3.3 is a CONTRAINDICATION to insulin.

When glc to 200 (in DKA) or 250-300 (in HHS) reduce infusion to 0.02-0.05U/kg/h IV or change SQ dosing to 0.1U/kg q2h with goal glc 150-200.

Never discontinue insulin prior to closure of anion gap!

If K <3.3 – hold insulin therapy and replete K with fluids – 40-60mEq/h to ½NS until K 3.3+ (assuming UOP 50cc/h+).

If K >5.3 – no K supplementation but check q2h.

3.3-5.3 – Give 20-30mEq per liter of 1/2NS goal K 4-5 (assuming UOP 50cc/h+).

Substantial losses in almost all 2/2 urine loss; shifts out of cells 2/2 insulin deficiency and hyperosmolality so K artifically elevated at presentation.

Whole body PO4 depletion is common though PO4 will be normal or elevated initially due to migration out of cells.

With treatment hypophosphatemia will develop usually without adverse effects in a self-ltd fashion.

No benefit to repleting PO4 unless cardiac dysfx/hemolytic anemia/resp depression, concentration <1.

pH <6.9 Consider HCO3 gtt (though small studies have shown minimal benefit…)

pH >7.0 No HCO3

Ketoacidosis resolved – AG is normal (<12) › Ketonemia/Ketonuria may persist >36h

without pt actually being in true ketoacidosis.

HHS pts are mentally alert and plasma osmolality is <315.

Pt is able to tolerate PO.

Initiate SQ insulin AT MEALTIME with a 1-2h taper of the gtt.

Insulin Naïve 0.5-0.8U/kg per day in sliding scale + long-acting regimen › 25% as long acting. › 25% as scheduled meal-time insulin › Sliding Scale

Known DM start at previous insulin regimen.

Cerebral edema › Very rare in adults but 40% mortality. › Sxs: ha, lethargy, decreased arousal

seizures, incontinence, brady, resp arrest, pupul changes.

› Mortality 20-40%. Prevented by following protocol, adding

dextrose to fluids when appropriate. Tx – unit, mannitol?, 3%NS?

Non-cardiogenic pulmonary edema › Hypoxemia 2/2 decreased osmotic

pressure migration of fluid into lungs. › If initial A-a gradient is widened on ABG,

higher risk of development of pulmonary edema.

A 23-year-old woman with type 1 diabetes mellitus is admitted to the hospital with a diagnosis of community-acquired pneumonia and lethargy. Before admission, her insulin pump therapy was discontinued because of confused mentation.

On physical examination, temperature is 37.5 °C (99.5 °F), blood pressure is 108/70 mm Hg, pulse rate is 100/min, and respiration rate is 24 min. There are decreased breath sounds in the posterior right lower lung. Neurologic examination reveals altered consciousness.

Sodium 130 meq/L (130 mmol/L) Potassium 5.0 meq/L (5.0 mmol/L) Chloride 100 meq/L (100 mmol/L) Bicarbonate 16 meq/L (16 mmol/L) Blood urea nitrogen 38 mg/dL (13.6 mmol/L) Creatinine 1.4 mg/dL (123.8 µmol/L Glucose 262 mg/dL (14.5 mmol/L)

Urine ketones Positive

Which of the following is the most appropriate next step in management?

A Add insulin glargine

B Add neutral protamine Hagedorn (NPH) insulin

C Implement a sliding scale for regular insulin

D Start an insulin drip

Questions?