Diabetic Ketoacidosis. Definition 2009 ADA consensus statement on DKA 2009 ADA consensus statement on DKA Life-threatening condition characterized by

Diabetic Diabetic KetoacidosisKetoacidosis

DefinitionDefinition

2009 ADA consensus statement on 2009 ADA consensus statement on DKADKA

Life-threatening condition Life-threatening condition characterized by characterized by hyperglycemia (glucose >250mg/dl)hyperglycemia (glucose >250mg/dl) Ketonemia or ketonuriaKetonemia or ketonuria Arterial pH <7.3Arterial pH <7.3 Bicarb < 15mmol/LBicarb < 15mmol/L

Epidemiology/StatisticsEpidemiology/Statistics

Annual incidence 5-8 episodes/1000 Annual incidence 5-8 episodes/1000 person-yearsperson-years

Mortality ~5% in adult DKAMortality ~5% in adult DKA Underlying precipitating illnessUnderlying precipitating illness

Annual hospitalizations for DKA – Annual hospitalizations for DKA – 100,000100,000

Annual hospitalization cost exceeds $1 Annual hospitalization cost exceeds $1 billion.billion.

PathogenesisPathogenesis

Insulin deficiency and/or resistanceInsulin deficiency and/or resistance Excess of counter-regulatory hormones Excess of counter-regulatory hormones

(glucagon, catecholamines, cortisol, GH)(glucagon, catecholamines, cortisol, GH) Increased gluconeogenesis, Increased gluconeogenesis,

glycogenolysis, proteolysis, lypolysisglycogenolysis, proteolysis, lypolysis Decreased glucose utilization in Decreased glucose utilization in

peripheral tissuesperipheral tissues

Pathogenesis (cont’d)Pathogenesis (cont’d)

Precipitating FactorsPrecipitating Factors

Infections (30-50%)Infections (30-50%) Medication non-compliance or Medication non-compliance or

inadequate treatment (30%)inadequate treatment (30%) New onset diabetes (20%)New onset diabetes (20%) Others- CVA, MI, trauma, pancreatitis, Others- CVA, MI, trauma, pancreatitis,

alcohol and drug abuse, pregnancy, alcohol and drug abuse, pregnancy, thyrotoxicosis, hypercortisolism, thyrotoxicosis, hypercortisolism, drugsdrugs

HistoryHistory

PolyuriaPolyuria PolydipsiaPolydipsia PolyphagiaPolyphagia Weight lossWeight loss

Nausea, vomitingNausea, vomiting Abdominal painAbdominal pain WeaknessWeakness Clouding Clouding

sensoriumsensorium

Physical ExamPhysical Exam

Evidence of Evidence of dehydrationdehydration dry mucus dry mucus

membranemembrane decreased skin decreased skin

turgorturgor orthostatic orthostatic

hypotensionhypotension decreased UOPdecreased UOP

Fruity odorFruity odor TachycardiaTachycardia HypotensionHypotension Kussmaul’s Kussmaul’s

respirationrespiration Altered mental statusAltered mental status ShockShock ComaComa

Diagnostic StudiesDiagnostic Studies

Blood work – Blood work – Chemistry panel, including Mg, PO4Chemistry panel, including Mg, PO4 Serum ketonesSerum ketones UA with urine ketonesUA with urine ketones ABG/VBGABG/VBG Serum OsmolalitySerum Osmolality Cbc with differentialCbc with differential Others: autoantibodies (anti-GAD, anti-islet Others: autoantibodies (anti-GAD, anti-islet

cells), C-peptide, A1c, fasting lipidcells), C-peptide, A1c, fasting lipid

Diagnostic Studies Diagnostic Studies (cont’d)(cont’d)

K+, Mg++, PO4-- depletion are usually K+, Mg++, PO4-- depletion are usually found. found. Initial serum K+ can be high due to Initial serum K+ can be high due to

extracellular shift of K+ secondary insulin extracellular shift of K+ secondary insulin deficiency and acidemiadeficiency and acidemia

Hyponatremia - osmotic pull of water into Hyponatremia - osmotic pull of water into intravascular space, vomiting with fluid intravascular space, vomiting with fluid loss and free water replacement, or loss and free water replacement, or severe hyperlipidemia severe hyperlipidemia (pseudohyponatremia)(pseudohyponatremia)


Cr may be falsely elevated due to Cr may be falsely elevated due to acetoacetate interference with measuring acetoacetate interference with measuring methodmethod

Leukocytosis is usually present, but usually Leukocytosis is usually present, but usually wbc <25K and no left shiftwbc <25K and no left shift

Amylase, lipase, and LFT can be elevated Amylase, lipase, and LFT can be elevated In rare cases, patients can have severe In rare cases, patients can have severe

hyperlipidemia, requiring sample dilution, hyperlipidemia, requiring sample dilution, leading to factitiously pseudohypo- or leading to factitiously pseudohypo- or normoglycemianormoglycemia


Ketones in DKA are acetoacetate, Ketones in DKA are acetoacetate, acetone and B hydroxybutyrate (BHB is acetone and B hydroxybutyrate (BHB is not detected by nitroprusside reaction)not detected by nitroprusside reaction)

During treatment for DKA, B During treatment for DKA, B hydroxybutyrate is converted to hydroxybutyrate is converted to acetoacetate, so test for ketones may acetoacetate, so test for ketones may become more strongly positive despite become more strongly positive despite improvement DKAimprovement DKA

EKGEKG CXR if pneumodrome presentCXR if pneumodrome present Blood cx, urine cx, throat cx if Blood cx, urine cx, throat cx if

indicatedindicated


DiagnosisDiagnosis

Diagnostic criteriaDiagnostic criteria BG >250, HCO3 <15, pH <7.3BG >250, HCO3 <15, pH <7.3 Ketonemia or ketonuriaKetonemia or ketonuria

Differential diagnosesDifferential diagnoses Ketoacidosis – alcohol, starvationKetoacidosis – alcohol, starvation AG metabolic acidosis - MUDPILESAG metabolic acidosis - MUDPILES

Diagnosis (cont’d)Diagnosis (cont’d)

TreatmentTreatment

1. IV fluid1. IV fluid Initially administer 1-2 L 0.9%NS bolusInitially administer 1-2 L 0.9%NS bolus Switch to 0.45% NS infusion at rate 300-Switch to 0.45% NS infusion at rate 300-

500 ml/hr if corrected Na+ is normal or 500 ml/hr if corrected Na+ is normal or highhigh

When BG < or = 200 mg/dL, switch to 5% When BG < or = 200 mg/dL, switch to 5% dextrose with 1/2NS at 150-250 ml/hrdextrose with 1/2NS at 150-250 ml/hr

Treatment (cont’d)Treatment (cont’d)

2. Insulin2. Insulin Traditionally, IV regular insulin is usedTraditionally, IV regular insulin is used Give loading dose at 0.1 units/kg as IV bolus Give loading dose at 0.1 units/kg as IV bolus

then infuse at rate 0.1 units/kg/hr then infuse at rate 0.1 units/kg/hr oror Start continuous infusion at 0.14 units/kg/hrStart continuous infusion at 0.14 units/kg/hr If BG does not fall by 50-70 mg/dl per hour, If BG does not fall by 50-70 mg/dl per hour,

double infusion dosedouble infusion dose Once BG reaches 200 mg/dl can reduce Once BG reaches 200 mg/dl can reduce

infusion rate (by 2-3units) to keep BG infusion rate (by 2-3units) to keep BG between 150-200 mg/dl until DKA resolvesbetween 150-200 mg/dl until DKA resolves


2. Insulin (cont’d)2. Insulin (cont’d) Transition to SC insulin Transition to SC insulin

Once AG < 12 meq/L [BG < 200 mg/dl, HCO3- Once AG < 12 meq/L [BG < 200 mg/dl, HCO3- >18 mEq/L, and pH > 7.3, AG < 12 meq/L]18 mEq/L, and pH > 7.3, AG < 12 meq/L]

if patient feels hungry and would like to eat,if patient feels hungry and would like to eat, not in NPO statusnot in NPO status


2. Insulin (cont’d)2. Insulin (cont’d) Start with both long- and rapid-acting insulin or Start with both long- and rapid-acting insulin or

around- the-clock regular insulinaround- the-clock regular insulin Give 60 minutes before discontinuing IV insulinGive 60 minutes before discontinuing IV insulin Long-acting – NPH or glargineLong-acting – NPH or glargine Rapid-acting – aspart, or lisproRapid-acting – aspart, or lispro Newly diagnosed patients usually requires 0.5 – 0.8 Newly diagnosed patients usually requires 0.5 – 0.8

units/kg/dayunits/kg/day Half given as long acting and remaining half given before mealsHalf given as long acting and remaining half given before meals

Check FBG qac and hs and supplement with sliding Check FBG qac and hs and supplement with sliding scale insulin to keep BG 100-150 mg/dLscale insulin to keep BG 100-150 mg/dL


2. Insulin (cont’d)2. Insulin (cont’d) SC or IM route can also be usedSC or IM route can also be used AdvantagesAdvantages

reduced nursing support, costreduced nursing support, cost Disadvantages Disadvantages

Pt’s discomfortPt’s discomfort Uncertain absorptionUncertain absorption


2. Insulin (cont’d)2. Insulin (cont’d) Prospective, randomized open trialProspective, randomized open trial Efficacy of subcutaneous lispro insulin (n = 20) compared to Efficacy of subcutaneous lispro insulin (n = 20) compared to

standard low dose intravenous regular insulin (n = 20) in standard low dose intravenous regular insulin (n = 20) in uncomplicated DKAuncomplicated DKA

No statistical differences in mean duration of treatment or No statistical differences in mean duration of treatment or amount of insulin administration, length of hospital stay, or amount of insulin administration, length of hospital stay, or mortalitymortality

Treatment of DKA in the ICU was associated with 39% higher Treatment of DKA in the ICU was associated with 39% higher hospitalization charges than was treatment with subcutaneous hospitalization charges than was treatment with subcutaneous lispro in a non-intensive care setting ($14,429 +/- $5243 vs. lispro in a non-intensive care setting ($14,429 +/- $5243 vs. $8801 +/- $5549, P <0.01).$8801 +/- $5549, P <0.01).

Am J Med 2004; 117: 291Am J Med 2004; 117: 291


2. Insulin (cont’d)2. Insulin (cont’d) Prospective, randomized, open trialProspective, randomized, open trial Efficacy of aspart insulin given at 1hr (SC-1h) or 2hr Efficacy of aspart insulin given at 1hr (SC-1h) or 2hr

(SC-2h) compared to IV regular insulin in uncomplicated (SC-2h) compared to IV regular insulin in uncomplicated DKADKA

45 patients – SC-1h, n =15, SC-2hr, n =15, IV-R, n = 1545 patients – SC-1h, n =15, SC-2hr, n =15, IV-R, n = 15 No statistical differences in mean duration of treatment No statistical differences in mean duration of treatment

or amount of insulin administration until correction of or amount of insulin administration until correction of hyperglycemia or resolution of ketoacidosishyperglycemia or resolution of ketoacidosis

No difference in mortality or length of hospital stayNo difference in mortality or length of hospital stay

Diabetes Care 2004; 27: 1873Diabetes Care 2004; 27: 1873


2. Insulin (cont’d)2. Insulin (cont’d) SC rapid-acting insulin SC rapid-acting insulin

Uncomplicated mild DKAUncomplicated mild DKA 0.3 U/kg, then 0.2 U/kg one hour later and then 0.3 U/kg, then 0.2 U/kg one hour later and then

q2 hrsq2 hrs

JCEM 2008; 93:1541.JCEM 2008; 93:1541.


3. Electrolytes3. Electrolytes PotassiumPotassium

If initial serum K+ If initial serum K+ >> 5.3 mEq/L, no 5.3 mEq/L, no supplementsupplement

If serum K+ between 3.3 and 5.3 mEq/L, give If serum K+ between 3.3 and 5.3 mEq/L, give 20-30 mEq K+ in each liter of IV fluid to keep 20-30 mEq K+ in each liter of IV fluid to keep K at 4-5mEq/LK at 4-5mEq/L

If serum K+ < 3.3 mEq/L, hold insulin and If serum K+ < 3.3 mEq/L, hold insulin and give 40 mEq K+ per hour until K+ give 40 mEq K+ per hour until K+ >> 3.3 3.3 mEq/LmEq/L


3. Electrolytes (cont’d)3. Electrolytes (cont’d) Bicarbonate Bicarbonate (100mmol in 400ml water with 20 (100mmol in 400ml water with 20

mmol KCL over 2 hours until pH >7)mmol KCL over 2 hours until pH >7) Give only if pH <6.9Give only if pH <6.9

PhosphatePhosphate Replace if serum phosphate < 1.0 mg/dLReplace if serum phosphate < 1.0 mg/dL

MagnesiumMagnesium Replace with IV MgSO4 if serum Mg++ <1.5 Replace with IV MgSO4 if serum Mg++ <1.5

mg/dLmg/dL


4. Monitoring frequency4. Monitoring frequency Initially q1-2 hrs for first few hours, Initially q1-2 hrs for first few hours,

then q2-4 hrs until stablethen q2-4 hrs until stable Flow sheetFlow sheet

DispositionDisposition

Discharge from ERDischarge from ER Mild DKA Mild DKA AlertAlert Able to tolerate oral intakeAble to tolerate oral intake CompliantCompliant Good social supportGood social support

AdmissionAdmission All other cases, including those with All other cases, including those with

comorbidities and poor social supportcomorbidities and poor social support

ComplicationsComplications

Cardiac arrhythmiasCardiac arrhythmias From electrolyte abnormalities or acidosisFrom electrolyte abnormalities or acidosis

HypoglycemiaHypoglycemia From overzealous insulin dosageFrom overzealous insulin dosage

HypokalemiaHypokalemia Due to administration of insulin and Due to administration of insulin and

bicarbonatebicarbonate Hyperglycemia/DKA recurrenceHyperglycemia/DKA recurrence

Due to discontinuation of IV insulin prematurely Due to discontinuation of IV insulin prematurely or failure to cover with SC insulin or failure to cover with SC insulin

Complications (cont’d)Complications (cont’d) Hyperchloremic metabolic acidosisHyperchloremic metabolic acidosis

Excessive Cl- from IV fluid Excessive Cl- from IV fluid Loss of HCO3- due to excretion of ketoanions as Na Loss of HCO3- due to excretion of ketoanions as Na

and K saltsand K salts Cerebral edemaCerebral edema

Due to osmotically-driven movement of water into CNSDue to osmotically-driven movement of water into CNS Occurs primarily in childrenOccurs primarily in children When plasma osmolality decreases too rapidlyWhen plasma osmolality decreases too rapidly Suspect when patient’s sensorium deteriorates or Suspect when patient’s sensorium deteriorates or

remains impaired despite resolution of DKAremains impaired despite resolution of DKA

Complications (cont’d)Complications (cont’d)

Pulmonary edemaPulmonary edema Patients with widened A-a gradients, wet Patients with widened A-a gradients, wet

crackles on lung examcrackles on lung exam Frequently monitor patients with cardiac Frequently monitor patients with cardiac

disease or renal insufficiency disease or renal insufficiency Venous and arterial thrombosisVenous and arterial thrombosis

DKA is a hypercoagulable state from endothelia DKA is a hypercoagulable state from endothelia injury, hypofibrogenolysis, and platelet injury, hypofibrogenolysis, and platelet hyperaggregationhyperaggregation

DVT prophylaxisDVT prophylaxis

PreventionPrevention Diabetic educationDiabetic education Sick day managementSick day management

Frequent measurement of blood glucoseFrequent measurement of blood glucose Home monitoring of ketonesHome monitoring of ketones Easily digestible liquid diet Easily digestible liquid diet Hold short acting insulin if not eatingHold short acting insulin if not eating Continue long acting insulinContinue long acting insulin Early access to professional adviceEarly access to professional advice

Case management for high-risk patientsCase management for high-risk patients

Management ErrorsManagement Errors

Not giving enough IV fluidNot giving enough IV fluid Overly rapid correction of Overly rapid correction of

hyperglycemiahyperglycemia Transitioning to SQ insulin too soonTransitioning to SQ insulin too soon Not allowing enough time for SQ Not allowing enough time for SQ

insulin to start working before insulin to start working before stopping IV insulinstopping IV insulin

Not repleting electrolytesNot repleting electrolytes

ReferencesReferences

1. Kitabchi, AE et al. “Hyperglycemic crises in adult 1. Kitabchi, AE et al. “Hyperglycemic crises in adult patients with diabetes: a consensus statement from the patients with diabetes: a consensus statement from the American Diabetes Association.” Diabetes Care 2006; American Diabetes Association.” Diabetes Care 2006; 29: 2739.29: 2739.

2. Kitabchi, AE et al. “Thirty years of personal 2. Kitabchi, AE et al. “Thirty years of personal experience in hyperglycemic crises: diabetic experience in hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state.” ketoacidosis and hyperglycemic hyperosmolar state.” JCEM 2008; 93: 1541.JCEM 2008; 93: 1541.

3. American Diabetes Association. “Hospital Admission 3. American Diabetes Association. “Hospital Admission Guidelines for Diabetes.” Diabetes Care 2004; Guidelines for Diabetes.” Diabetes Care 2004; 27(Suppl 1): S103.27(Suppl 1): S103.

4. Charfen, MA. “Diabetic Ketoacidosis.” Emerg Med 4. Charfen, MA. “Diabetic Ketoacidosis.” Emerg Med Clin N Am 2005; 23:609.Clin N Am 2005; 23:609.

References (cont’d)References (cont’d) 5. Umpierrez, GE. “Treatment of Diabetic 5. Umpierrez, GE. “Treatment of Diabetic

Ketoacidosis with Subcutaneous Insulin Aspart.” Ketoacidosis with Subcutaneous Insulin Aspart.” Diabetes Care 2004;27:1873.Diabetes Care 2004;27:1873.

6. Umpierrez, GE. “Efficacy of subcutaneous insulin 6. Umpierrez, GE. “Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosisthe treatment of patients with diabetic ketoacidosis..” ” Am J Med 2004; 117 (5):291.Am J Med 2004; 117 (5):291.

7. Kitabchi, AE. “Management of Hyperglycemic 7. Kitabchi, AE. “Management of Hyperglycemic Crises in Patients with Diabetes.” Diabetes Care Crises in Patients with Diabetes.” Diabetes Care 2001;24:131.2001;24:131.

8. American Diabetes Association. “Hyperglycemic 8. American Diabetes Association. “Hyperglycemic Crises in Diabetes.” Diabetes Care 2004; 27 (Suppl 1): Crises in Diabetes.” Diabetes Care 2004; 27 (Suppl 1): S94-102.S94-102.

Documents

Diabetic Ketoacidosis. Definition 2009 ADA consensus statement on DKA 2009 ADA consensus statement on DKA Life-threatening condition characterized by