Diabetic ketoacidosis: Difference between revisions
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== Background  ==
== Background  ==
===Epidemiology===
The mortality rate of DKA since the advent of insulin is approximately 2-5%<ref>Lebovitz HE: Diabetic ketoacidosis.  Lancet 1995; 345: 767-772.</ref>


*Hyperglycemia  
===Pathophysiology===
**Leads to osmotic diuresis  
;Definition:  Hyperglycemia (glucose > 250 mg/dl), Acidosis (pH < 7.3), and Ketosis
***Loss of fluid, Na, Cl, K, Phos, Ca, Mg
 
*Acidosis  
====Hyperglycemia====
**Due to lipolysis / accumulation of of ketoacids (represented by anion gap showing conjugate bases)
*Leads to osmotic diuresis and depletion of electrolytes including sodium, magnesium, calcium and phosphorous.
**Compensatory respiratory alkalosis  
*Further dehydration impairs glomerular filtration rate (GFR) and contributes to acute renal failure
**Breakdown of adipose &gt; prostaglandin I2, E2
 
***Prostaglandins + acidosis = vasodilation
====Acidosis====
***Prostaglandins cause N/V/abd pain
*Due to lipolysis / accumulation of of ketoacids (represented by anion gap showing conjugate bases)
*Dehydration  
*Compensatory respiratory alkalosis  
**Causes Renin system activation  
*Breakdown of adipose creates first acetoacetate leading to conversion to beta-hydroxybutyrate
***K and ketoanion loss (in exchange for chloride)  
 
****Worsens metabolic acidosis
====Dehydration====
*Causes Renin system activation in addition to the osmotic diuresis
*Cation loss (in exchange for chloride) worsens metabolic acidosis


=== Causes  ===
=== Causes  ===
 
#Insulin or oral hypoglycemic medication non-compliance  
*Insulin non-compliance  
#Infection  
*Infection  
#[[Cardiac Ischemia]]  
*[[Cardiac Ischemia]]  
#Intra-abdominal infections
*Intra-abd process
#Steroid use
*Meds
#[[ETOH Abuse]]  
**Steroids, antipsychotics, thiazides
#Drug abuse  
*[[ETOH Abuse]]  
#Pregnancy  
*Drug abuse  
#[[Hyperthyroidism]]  
*Pregnancy  
#[[GI Hemorrhage]]
*[[Hyperthyroidism]]  
*[[GI Hemorrhage]]


== History ==
== History ==
*Are any Sx consistent with hyperglycemia, acidosis, or cerebral edema?
*Perform a thorough neurologic exam since Cerebral Edema increases mortality significantly especially in children
*Does pt have h/o DM? If so, prior episodes of DKA or HHS?
*Assess prior history of DKA or hyperglycemic episodes
*Is there associated infection?
*Is there associated infection?
*Is there another associated illness/ppt?
*Is there another associated illnesses or risk factors
**[[CVA]], [[MI]], [[PE]], [[Pancreatitis]], [[Renal Failure]], [[GI Bleed]], [[ETOH]]/drug use
**[[CVA]], [[MI]], [[PE]], [[Pancreatitis]], [[Renal Failure]], [[GI Bleed]], [[ETOH]]/drug use
*Has pt taken adequate insulin?
*Has the patient been compliant with insulin use?
*Pt on meds that could ppt DKA?
*Any recent medications started which could cause DKA


== Workup  ==
== Workup  ==
*CBC  
*CBC  
*Chem 10  
*Chem 10  
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*hCG  
*hCG  
*ECG  
*ECG  
*VBG (often dose not change management unless suspect inadequate respiratory compensation)
*VBG (equivalent to ABG for assessment of acid-base status)<ref name="British DKA">Savage MW, Datary KK, Culvert A, Ryman G, Rees JA, Courtney CH, Hilton L, Dyer PH, Hamersley MS; Joint British Diabetes Societies.  Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis. Diabet Med. 2011 May;28(5):508-15.</ref><ref>Gokel, Yuksel; Paydas, Saime; Koseoglu, Zikret; Alparslan, Nazan; Seydaoglu, Gulsah: Comparison of Blood Gas and Acid-Base Measurements in Arterial and Venous Blood Samples in Patients with Uremic Acidosis and Diabetic Ketoacidosis in the Emergency Room.  American Journal of Nephrology 2000; 20:319-323.</ref>
**Venous pH ~ 0.03 lower than arterial pH  
**Venous pH ~ 0.03 lower than arterial pH  
**Verify that respiratory compensation is as expected  
**Verify that respiratory compensation is as expected  
*CXR
*Chest xray is indicated if exam concerning for respiratory source of infection


== Diagnosis  ==
== Diagnosis  ==
 
# Blood Sugar>250
*Diagnosis = BS &gt;250, AG &gt;10, bicarb &lt;15, pH &lt;7.3, mod ketones
#AG>12
**BS may be lower if impaired gluconeogenesis (liver failure)  
#Bicarb <15
**Bicarb may be normal if concurrent alkalosis (e.g. vomiting)  
#pH <7.2
***In this case an elevated gap may be the only clue  
#ketonemia and ketonuria
*Severity
*BS may be lower if there is impaired gluconeogenesis (liver failure patients or severe alcoholics)  
**Mild (ketosis): gap &lt;12
*Bicarb may be normal if there is concurrent alkalosis (e.g. vomiting)  
**Mod: gap 12-18
**In this case an elevated gap may be the only clue with anion gaps > 18 in severe ketonemia
**Severe: gap &gt;18


== Treatment  ==
== Treatment  ==
=== Volume Repletion===
*Most important step in treatment since osmotic diuresis is the major driving force<ref name="British DKA"></ref>
*Administer 20-30cc/kg bolus during the first hour
*Most adult patients are  3-6L depleted
*[[Hyponatremia]] is a result of dilution. Start Normal Saline @ 250-500ml/hr
*If [[Hypernatremic]] then consider starting 1/2NS @ 250-500ml/hr after initial fluid bolus
*When blood sugar(BS) < 250 switch to D5<sub>1/2</sub>NS@ 150-200 ml/hr(+/- KCl)


*Volume then potassium then insulin
=== Insulin  ===
*'''Check Potassium prior to insulin treatment!'''<ref>Aurora S, Cheng D, Wyler B, Menchine M. Prevalence of hypokalemia in ED patients with diabetic ketoacidosis. Am J Emerg Med 2012; 30: 481-4.</ref>
*If K <3.5mEq/L do not administer insulin.  If the potassium is < 5.5 mEq/L but > 3.5 mEq/L, then start potassium repletion along with your insulin.<ref>*http://emupdates.com/2010/07/15/correction-of-critical-hypokalemia/</ref>


=== Labs/Monitoring ===
*Insulin is required to stop the ketosis but a a bolus dose is unnecessary and may contribute to increased hypoglycemic episodes<ref>Goyal N, Miller J, Sankey S, Mossallam U. Utility of Initial Bolus insulin in the treatment of diabetic ketoacidosis.  Journal of Emergency Medicine, Vol 20:10, p30.</ref>


*Glucose check Q1hr
*Expect BS to fall by 50-100 mg/dL per hr if you administer 0.1units/kg/hr of insulin
*Chem 10 Q4hr (initially Q2hr)
*Refractory hyperglycemia may be due to an associated infectious process contributing to the DKAn
*Check pH prn based on clinical status (eval respiratory compensation)
*Check appropriateness of insulin dose Q1hr (see below)
*Corrected Na:
**Add 1.6 for each glucose of 100 &gt;100
 
=== Fluids  ===
 
*Most pts 3-6L depleted
*If severe hypovolemia: 1L NS/hr for up to 3 hr
*If mild dehydration then evaluate corrected Na+
**If Normal Na or [[Hypernatremic]]: 1/2NS @ 250-500ml/hr  
**If [[Hyponatremic]]: NS @ 250-500ml/hr
*When BS &lt; 250 switch to D51/2NS@ 150-200 ml/hr(+/- KCl)
*Bolus NS as needed for unstable VS
 
=== Insulin  ===


*Check K prior to insulin Tx!
====IV Insulin Regimen:====
**If K &lt; 3.3 do not administer insulin
#When BS <200, reduce to 0.02-0.05 U/kg/hr IV OR give subQ 0.1 U/kg q2hr  
*IV Route
#Maintain BS between 150 and 200 until resolution of DKA  
**IV gtt 0.1 U/kg/hr
#Continue IV infusion for 2 hrs after subcutaneous insulin tx is begun  
***Bolus dose unnecessary
#SubQ route (appropriate only for mild DKA)  
**Expect BS fall by 50-100 mg/dL per hr
;Do not stop insulin infusion until AG normalized AND bicarb normalized  
***If BS, pH, AG not improving after adequate hydration and UOP, then double infusion rate Q1hr until achieved
***Refractoriness often due to infection
**When BS &lt;200, reduce to 0.02-0.05 U/kg/hr IV OR give subQ 0.1 U/kg q2hr  
***Maintain BS between 150 and 200 until resolution of DKA  
***Continue IV infusion for 1-2 hr after SC insulin tx is begun  
*SubQ route (appropriate only for mild DKA)  
**Insulin lispro or aspart 0.3 U/kg initially
***0.2 U/kg one hr later
****0.2 U/kg q2hr thereafter
**If BS does not decrease by 50-100/hr then double dose qhr until achieved
*Pitfalls
*Do not stop insulin infusion until AG normalized AND bicarb normalized  
*Excess Cl from NS bolus' artificially raises serum Cl&nbsp;


=== Potassium  ===
====SubQ Insulin Regimen:====
;SubQ(SC) 1hr Protocol<ref>Umpierrez G. et al. Treatment of diabetic ketoacidosis with subcutaneous insulin aspart. Diabetes Care. 2004 Aug;27(8):1873-8 [PDF http://care.diabetesjournals.org/content/27/8/1873.full.pdf]</ref>
#Initial dose SC Aspart: 0.3 units/kg body wt, followed by
## SC aspart insulin at 0.1 units/kg every hour
##When blood glucose <250 mg/dl (13.8 mmol/l), change IV fluids to D5 0.45% saline and reduce SC aspart insulin to 0.05
units/kg/hr to keep glucose at 150mg/dl (11 mmol/l) until resolution of DKA.


*Ensure adequate urine output before giving K
=== Electrolyte Repletion  ===
*Prevent [[Hypokalemia]]  
#[[Diabetic_Ketoacidosis_(DKA)#Insulin|Potassium repletion]] is most important
*&gt;5.5: don't give, but recheck q2hr
#Sodium – Serum concentration diluted as a result of osmotic gradient of glucose pulling more water into extracellular space.
*3.3-5.5: give 30 meq/hr in each liter bag
#[[Hypophasphatemia]]: If < 1.0 mEq/L, start repletion.
**1/2NS is preferred b/c adding 30meq to NS = hypertonic soln
##Severe hypophosphatemia can cause cardiac and respiratory dysfunction
*&lt;3.3: hold insulin and give 30 meq/hr until K &gt;3.3
#[[Hypomagnesemia]] – All patients who are hypokalemic are hypomagnesemic. Replete together as long as kidney function intact.


=== Bicarb  ===
=== Bicarb  ===
*No benefit has been demonstrated from Sodium Bicarbonate therapy in acidosis cause by DKA<ref>[[EBQ:Sodium Bicarbonate use in DKA]]</ref>
*Adding sodium bicarb to a patient's fluids requires to increase the respiratory rate to expel the converted CO<sub>2</sub>
*Patients with DKA generally have maximally elevated respiratory rates and cannot increase.  The bicarbonate administration then further increases the patient's acidoses.  <ref>Villon A, Zuni F, Plafond P et al.  Does bicarbonate therapy improve management of severe diabetic ketoacidosis?  Crit Care Med 1999; 27: 2690-2693.</ref><ref>Okuda Y, Drogue HJ, Field JB et al.  Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis.  J Clinical Endocrinology Metabolism 1996; 81: 314-320.</ref>


*Consider for pH &lt;6.9 AND:
=== DKA Refractory to Treatment===
**Decreased contractility
Assess for [[Diabetic Ketoacidosis (DKA)#Causes|other causes of DKA]]
**Hypotension
**Severe [[Hyperkalemia]]  
**Coma
*100 meq NaHCO3 in 400mL H2O @ 200 mL/hr
**Dose as needed until pH &gt; 7.00


=== Phosphate  ===


*[[Hypophosphatemia]] following insulin tx usually asymptomatic
=== Labs/Monitoring ===
**Repletion is associated with [[HypoCa]] and [[HypoMg]]
*Glucose check Q1hr
*Consider repletion (KPO4 20-30 meq/L)if:
*Chem 10 Q4hr (initially Q2hr)
**Phosphate &lt;1.0
*Check pH prn based on clinical status (eval respiratory compensation)
**Cardiac dysfunction
*Check appropriateness of insulin dose Q1hr (see below)
**Respiratory dysfunction
*Corrected Electrolytes
**Evidence of hemolysis or rhabdo
 
<br>
 
=== '''DKA Refractory to Treatment'''  ===
 
Ketoacidosis/ AG persists &amp; BG 70 to 150 mg/dL:<br>
 
*Start D10W or D10NS @ 150 - 250 mL/h and/or consider reducing insulin rate by 1/2.
**Keep Serum glucose between 150 – 200 mg/dL
 
Ketoacidosis/ AG persists &amp; BG &lt; 70 mg/dL:<br>
 
*Hold insulin X 15 min and&nbsp;Bolus 1 AMP D50 IVP<br>
*Recheck FS BG if &lt; 70, retreat w/ 1 AMP D50 IVP and repeat FS BG<br>
*Once FS BG &gt; 70 mg/dL, restart&nbsp;Insulin @ 1⁄2 prior infusion rate
*Start D10W or D10NS (If volume&nbsp;depleted)@ 150 - 250 mL/h
 
 
 
*Keep Serum glucose between 150 –200 mg/dL
*If cannot maintain glucose &gt; 150 mg/dL despite D10 and diet then titrate insulin down to a minimum of 0.5 unit/hr


== Complications  ==
== Complications  ==
*Cerebral Edema  
*Cerebral Edema  
**Almost all affected pts are &lt;20yr  
**Almost all affected pts are <20yr  
**Associated with initial bicarb level; not rate of glucose drop  
**Associated with initial bicarb level; not rate of glucose drop  
**Premonitory symptoms:  
**Premonitory symptoms:  
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***Incontinence  
***Incontinence  
***[[Mental Status Change]] / [[Seizure]]  
***[[Mental Status Change]] / [[Seizure]]  
**Treatment  
**Treatment should be performed in conjunction with primary team recommendations
***Mannitol IV 1-2gm/kg OR  
***Mannitol IV 1-2gm/kg OR  
***3% NS 5-10mL/kg over 30min  
***3% NS 5-10mL/kg over 30min  
*Noncardiogenic pulmonary edema
*Noncardiogenic pulmonary edema


=== Sliding Scale ===
=== Sliding Scale ===
 
*200-250 = 4u sq  
*200-250 = 4u sq  
*251-300 = 6  
*251-300 = 6  
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== Treatment Algorithm  ==
== Treatment Algorithm  ==
[[Image:ADA DKA.gif]]


== See Also  ==
== See Also  ==
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== Source  ==
== Source  ==
*Tintinalli's
<references/>
*UpToDate
 
*EBmedicine.net


Image: UpToDate


[[Category:Endo]]
[[Category:Endo]]

Revision as of 04:18, 29 April 2014

Background

Epidemiology

The mortality rate of DKA since the advent of insulin is approximately 2-5%[1]

Pathophysiology

Definition
Hyperglycemia (glucose > 250 mg/dl), Acidosis (pH < 7.3), and Ketosis

Hyperglycemia

  • Leads to osmotic diuresis and depletion of electrolytes including sodium, magnesium, calcium and phosphorous.
  • Further dehydration impairs glomerular filtration rate (GFR) and contributes to acute renal failure

Acidosis

  • Due to lipolysis / accumulation of of ketoacids (represented by anion gap showing conjugate bases)
  • Compensatory respiratory alkalosis
  • Breakdown of adipose creates first acetoacetate leading to conversion to beta-hydroxybutyrate

Dehydration

  • Causes Renin system activation in addition to the osmotic diuresis
  • Cation loss (in exchange for chloride) worsens metabolic acidosis

Causes

  1. Insulin or oral hypoglycemic medication non-compliance
  2. Infection
  3. Cardiac Ischemia
  4. Intra-abdominal infections
  5. Steroid use
  6. ETOH Abuse
  7. Drug abuse
  8. Pregnancy
  9. Hyperthyroidism
  10. GI Hemorrhage

History

  • Perform a thorough neurologic exam since Cerebral Edema increases mortality significantly especially in children
  • Assess prior history of DKA or hyperglycemic episodes
  • Is there associated infection?
  • Is there another associated illnesses or risk factors
  • Has the patient been compliant with insulin use?
  • Any recent medications started which could cause DKA

Workup

  • CBC
  • Chem 10
  • UA
  • Serum ketones: Beta-hydroxybutrate, acetoacetate
  • hCG
  • ECG
  • VBG (equivalent to ABG for assessment of acid-base status)[2][3]
    • Venous pH ~ 0.03 lower than arterial pH
    • Verify that respiratory compensation is as expected
  • Chest xray is indicated if exam concerning for respiratory source of infection

Diagnosis

  1. Blood Sugar>250
  2. AG>12
  3. Bicarb <15
  4. pH <7.2
  5. ketonemia and ketonuria
  • BS may be lower if there is impaired gluconeogenesis (liver failure patients or severe alcoholics)
  • Bicarb may be normal if there is concurrent alkalosis (e.g. vomiting)
    • In this case an elevated gap may be the only clue with anion gaps > 18 in severe ketonemia

Treatment

Volume Repletion

  • Most important step in treatment since osmotic diuresis is the major driving force[2]
  • Administer 20-30cc/kg bolus during the first hour
  • Most adult patients are 3-6L depleted
  • Hyponatremia is a result of dilution. Start Normal Saline @ 250-500ml/hr
  • If Hypernatremic then consider starting 1/2NS @ 250-500ml/hr after initial fluid bolus
  • When blood sugar(BS) < 250 switch to D51/2NS@ 150-200 ml/hr(+/- KCl)

Insulin

  • Check Potassium prior to insulin treatment![4]
  • If K <3.5mEq/L do not administer insulin. If the potassium is < 5.5 mEq/L but > 3.5 mEq/L, then start potassium repletion along with your insulin.[5]
  • Insulin is required to stop the ketosis but a a bolus dose is unnecessary and may contribute to increased hypoglycemic episodes[6]
  • Expect BS to fall by 50-100 mg/dL per hr if you administer 0.1units/kg/hr of insulin
  • Refractory hyperglycemia may be due to an associated infectious process contributing to the DKAn

IV Insulin Regimen:

  1. When BS <200, reduce to 0.02-0.05 U/kg/hr IV OR give subQ 0.1 U/kg q2hr
  2. Maintain BS between 150 and 200 until resolution of DKA
  3. Continue IV infusion for 2 hrs after subcutaneous insulin tx is begun
  4. SubQ route (appropriate only for mild DKA)
Do not stop insulin infusion until AG normalized AND bicarb normalized

SubQ Insulin Regimen:

SubQ(SC) 1hr Protocol[7]
  1. Initial dose SC Aspart: 0.3 units/kg body wt, followed by
    1. SC aspart insulin at 0.1 units/kg every hour
    2. When blood glucose <250 mg/dl (13.8 mmol/l), change IV fluids to D5 0.45% saline and reduce SC aspart insulin to 0.05

units/kg/hr to keep glucose at 150mg/dl (11 mmol/l) until resolution of DKA.

Electrolyte Repletion

  1. Potassium repletion is most important
  2. Sodium – Serum concentration diluted as a result of osmotic gradient of glucose pulling more water into extracellular space.
  3. Hypophasphatemia: If < 1.0 mEq/L, start repletion.
    1. Severe hypophosphatemia can cause cardiac and respiratory dysfunction
  4. Hypomagnesemia – All patients who are hypokalemic are hypomagnesemic. Replete together as long as kidney function intact.

Bicarb

  • No benefit has been demonstrated from Sodium Bicarbonate therapy in acidosis cause by DKA[8]
  • Adding sodium bicarb to a patient's fluids requires to increase the respiratory rate to expel the converted CO2
  • Patients with DKA generally have maximally elevated respiratory rates and cannot increase. The bicarbonate administration then further increases the patient's acidoses. [9][10]

DKA Refractory to Treatment

Assess for other causes of DKA


Labs/Monitoring

  • Glucose check Q1hr
  • Chem 10 Q4hr (initially Q2hr)
  • Check pH prn based on clinical status (eval respiratory compensation)
  • Check appropriateness of insulin dose Q1hr (see below)
  • Corrected Electrolytes

Complications

  • Cerebral Edema
    • Almost all affected pts are <20yr
    • Associated with initial bicarb level; not rate of glucose drop
    • Premonitory symptoms:
    • Treatment should be performed in conjunction with primary team recommendations
      • Mannitol IV 1-2gm/kg OR
      • 3% NS 5-10mL/kg over 30min
  • Noncardiogenic pulmonary edema

Sliding Scale

  • 200-250 = 4u sq
  • 251-300 = 6
  • 301-350 = 8
  • 351-400 = 10

Treatment Algorithm

See Also

Source

  1. ↑ Lebovitz HE: Diabetic ketoacidosis. Lancet 1995; 345: 767-772.
  2. ↑ 2.0 2.1 Savage MW, Datary KK, Culvert A, Ryman G, Rees JA, Courtney CH, Hilton L, Dyer PH, Hamersley MS; Joint British Diabetes Societies. Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis. Diabet Med. 2011 May;28(5):508-15.
  3. ↑ Gokel, Yuksel; Paydas, Saime; Koseoglu, Zikret; Alparslan, Nazan; Seydaoglu, Gulsah: Comparison of Blood Gas and Acid-Base Measurements in Arterial and Venous Blood Samples in Patients with Uremic Acidosis and Diabetic Ketoacidosis in the Emergency Room. American Journal of Nephrology 2000; 20:319-323.
  4. ↑ Aurora S, Cheng D, Wyler B, Menchine M. Prevalence of hypokalemia in ED patients with diabetic ketoacidosis. Am J Emerg Med 2012; 30: 481-4.
  5. ↑ *http://emupdates.com/2010/07/15/correction-of-critical-hypokalemia/
  6. ↑ Goyal N, Miller J, Sankey S, Mossallam U. Utility of Initial Bolus insulin in the treatment of diabetic ketoacidosis. Journal of Emergency Medicine, Vol 20:10, p30.
  7. ↑ Umpierrez G. et al. Treatment of diabetic ketoacidosis with subcutaneous insulin aspart. Diabetes Care. 2004 Aug;27(8):1873-8 [PDF http://care.diabetesjournals.org/content/27/8/1873.full.pdf]
  8. ↑ EBQ:Sodium Bicarbonate use in DKA
  9. ↑ Villon A, Zuni F, Plafond P et al. Does bicarbonate therapy improve management of severe diabetic ketoacidosis? Crit Care Med 1999; 27: 2690-2693.
  10. ↑ Okuda Y, Drogue HJ, Field JB et al. Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis. J Clinical Endocrinology Metabolism 1996; 81: 314-320.
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