Diabetic ketoacidosis: Difference between revisions
 
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{{Adult top}} [[diabetic ketoacidosis (peds)]]
==Background==
==Background==
*Hyperglycemia
*Patients in DKA are almost always K+ depleted despite initially fairly normal K+.
**Leads to osmotic diuresis
**This is due to extracellular shift of K+ due to acidosis as well as insulin infusion, which increases uptake of K+ intracellularly.
***Loss of fluid, Na, Cl, K, Phos, Ca, Mg
*Acidosis
**Due to lipolysis / loss of ketoanions
**Causes respiratory alkalosis
**Breakdown of adipose > prostaglandin I2, E2
***Prostaglandins + acidosis = vasodilation
***Prostaglandins cause N/V/abd pain
*Dehydration
**Causes Renin system activation
***K and ketoanion loss (in exchange for chloride)
****Worsens metabolic acidosis


===Causes===
===Epidemiology===
*Insulin non-compliance
*Mortality rate approximately 2-5%<ref>Lebovitz HE: Diabetic ketoacidosis.  Lancet 1995; 345: 767-772.</ref>
*Infection
*Ischemia
*Intra-abd process
*Meds
**Steroids, antipsychotics, thiazides
*ETOH/drug abuse
*Pregnancy
*Hyperthyroidism
*GI hemorrhage


==Diagnosis==
===Pathophysiology===
*Diagnosis = BS >250, AG >10, bicarb <15, pH <7.3, mod ketones
''Defining features include '''hyperglycemia''' (glucose > 200mg/dl), '''acidosis''' (pH < 7.3), and '''ketonemia'''''
**BS may be lower if impaired gluconeogenesis (liver failure)
**Bicarb may be normal if concurrent alkalosis (e.g. vomiting)
***In this case an elevated gap may be the only clue
*Severity
**Mild (ketosis): gap <12
**Mod: gap 12-18
**Severe: gap >18


==Workup==
====[[Hyperglycemia]]====
*Leads to osmotic diuresis and depletion of electrolytes including sodium, potassium, magnesium, calcium and phosphorus.
*Further dehydration impairs glomerular filtration rate (GFR) and contributes to acute renal failure
*Hypokalemia may inhibit insulin release
 
====[[Acidosis]]====
*Due to insulin deficiency -> lipolysis / accumulation of of ketoacids (represented by increased anion gap)
*Compensatory respiratory alkalosis (i.e. tachypnea and hyperpnea - Kussmaul breathing)
*Breakdown of adipose creates first acetoacetate leading to conversion to beta-hydroxybutyrate
 
====[[Dehydration]]====
*Causes activation of RAAS in addition to the osmotic diuresis
*The initial serum values for electrolytes such as K+ may be higher than actual body stores
*Cation loss (in exchange for chloride) worsens metabolic acidosis
 
==Clinical Features==
{{DKA clinical features}}
 
==Differential Diagnosis==
===Causes of DKA===
*[[Insulin]] or oral hypoglycemic medication non-compliance (or insulin pump malfunction)
*Infection
*[[Cardiac Ischemia]]
*Intra-abdominal infections
*[[Steroid]] use
*[[ETOH Abuse]]
*[[Toxicologic exposure]]
*[[Pregnancy]]
*[[Hyperthyroidism]]
*[[GI Hemorrhage]]
*[[CVA]]
*[[PE]]
*[[Pancreatitis]]
*[[Renal Failure]]
*[[GI Bleed]]
*[[Alcoholic Ketoacidosis]]
*[[SGLT-2 inhibitors]] (euglycemic DKA)
 
{{Hyperglycemia DDX}}
 
==Evaluation==
===Workup===
''Workup to confirm diagnosis and search for possible inciting causes (e.g. infection, [[ACS]])''
*CBC
*CBC
*Chem 10
*BMP
*UA
*Blood glucose
*Serum ketones (e.g. beta-hydroxybutyrate and/or acetone)
*Mag
*Phos
*[[VBG]]/[[ABG]]
*Consider [[ECG]], [[urinalysis]], [[chest X-ray]], [[blood cultures]]
 
===Diagnosis===
''Diagnosis is made based on the presence of '''acidosis''' (e.g. venous pH < 7.3 or HCO3 <18) and '''ketonemia''' (e.g. >3mmol/L BOH or ketonuria) in the setting of diabetes (e.g. glucose >200mg/dl)'' <ref>Glaser N, Fritsch M, Priyambada L, et al. ISPAD clinical practice consensus guidelines 2022: Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes 2022; 23:835.</ref>
 
====Basic Laboratory Findings====
*Blood Glucose
**Capillary blood sugar >200mg/dL
**Blood sugar may not be very elevated if there is impaired gluconeogenesis (eg liver failure, severe alcoholism) or patient is taking a [[SGLT-2 Inhibitor]] <ref>Peters AL et al. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care 2015 Sep; 38(9): 1687-1693.</ref>
*Elevated [[Anion Gap]]
**Bicarb may be normal due to compensatory and contraction alkalosis so the elevated anion gap or ketonuria may be the only clues to the DKA
*Serum ketones
*Serum ketones
*hCG
**Beta hydroxybutyrate will be elevated
*ECG
 
*VBG
====Blood Gas====
**Venous pH ~ 0.03 lower than arterial pH
''No need to perform Arterial blood gas. Venous blood gas is sufficient<ref>Ma OJ, Rush MD, Godfrey MM, Gaddis G. Arterial blood gas results rarely influence emergency physician management of patients</ref>''
**Verify that respiratory compensation is as expected
*Difference in pH from VBG vs ABG  will be ±0.02pH units<ref>Kelly AM et al. Review Article – Can Venous Blood Gas Analysis Replace Arterial in Emergency Medical Care. Emery Med Australas 2010; 22: 493 – 498.</ref><ref>Ma OJ et al. Arterial Blood Gas Results Rarely Influence Emergency Physician Management of Patients with Suspected Diabetic Ketoacidosis. Acad Emerg Med Aug 2003; 10(8): 836 – 41. </ref> <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 Y, et al. 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>
*CXR
 
====Urinary analysis (ketonuria)====
*[[Urinalysis]] may be a useful screening test early in DKA, if serum ketones not available
**However, may give a false negative for ketones later in DKA, as acetoacetate is converted to beta-hydroxybutyrate the urinary ketones may turn negative<ref>Stojanovic, V. Sherri Ihle. Role of beta-hydroxybutyric acid in diabetic ketoacidosis: A review. Can Vet J. 2011 Apr; 52(4): 426–430. </ref>
 
====End Tidal CO2====
''Strongly consider capnography for respiratory distress<ref>Nagler J et al. Capnography: A valuable tool for airway management. Emerg Med Clin North Am, 26(4):881, Nov 2008.</ref>''
*ETCO2 can be used for bedside assessment of DKA in pts with glucose>550<ref>Chebl BR, Madden B, Belsky J, et al. Diagnostic value of end tidal capnography in patients with hyperglycemia in the emergency department. BCM Emerg Med. 2016; 16 (1).</ref>
**An ETCO2 of ≥35 is 100% sensitive to rule out DKA
**An ETCO2 of ≤21 is 100% specific to diagnosis DKA
 
==Management==
[[File:DKA management.png|thumb|Algorithm for the management of diabetic ketoacidosis]]
*If the patient has an insulin pump, make sure it is shut off or disconnected
 
===Volume Repletion===
*Administer 20-30cc/kg [[lactated ringers]] bolus during the first hour
**Most important step in treatment since osmotic diuresis is the major driving force<ref name="British DKA"></ref>
**Most adult patients are  3-6L depleted
**Increased systemic perfusion may transport insulin to previously unreached receptor sites, inhibiting ketogenesis
**Increased renal perfusion promotes renal hydrogen ion loss
**Use of LRs is preferred over NS <ref>Carrillo et al. Balanced Crystalloid Versus Normal Saline as Resuscitative Fluid in Diabetic Ketoacidosis. https://pubmed.ncbi.nlm.nih.gov/34986659/</ref>,<ref>Self et al. Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis: A Subgroup Analysis of Cluster Randomized Clinical Trials. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2772993/</ref>
**When blood sugar(BS) < 250-300 add a D10 infusion at an equal rate to the LR using a single IV line <ref>https://emcrit.org/ibcc/dka/</ref>
**Patients can eat and drink if mental status is intact <ref>Lipatov, K. et al. Early vs late oral nutrition in patients with diabetic ketoacidosis admitted to a medical intensive care unit. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347656/</ref>
 
===[[Electrolyte Repletion]]===
*Potassium (most important!)<ref>*http://emupdates.com/2010/07/15/correction-of-critical-hypokalemia/</ref>
**<3.5mEq/L:
***Start potassium repleation: 20-30 mEq KCl to IVF/hr
***Do not administer insulin (to avoid worsening of hypokalemia)
**>3.5mEq/L and <5.5 mEq/L:
***Start potassium repleation: 20-30 mEq KCl to IVF/hr
***May start insulin (see below)
**>5.5 mEq/L:
***Hold potassium repletion and recheck electroltyes after initiaton of insulin (see below)
*Sodium
**[[Hyponatremia]]
***Correct for hyperglycemia
****Na+ decreases by 1.6mEq/L for every 100mg/dL increase in glucose (ie pseudohyponatremia)
***If truly hyponatraemic, start NS 250-500ml/hr
**[[Hypernatremia]]
***Consider Lactated Ringers
*[[Hypophosphatemia]]
**<1.0 mEq/L, start repletion:
***IV K2PO4 at 1mL/hour (contains 4.4meqK+ & 93mg phos)
***Severe hypophosphatemia can cause cardiac and respiratory dysfunction
*[[Hypomagnesemia]]
**Mg<2.0mg/DL, start repletion:
***2g MgSO4 IV over 1h
 
===[[Insulin]] Overview===
*'''Check potassium prior to insulin treatment (see above)! Do not administer insulin until potassium supplementation is underway.'''<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>
*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>
*If the patient comes in wearing an insulin pump, turn off the pump and remove the subcutaneous catheter.
*Expect BS to fall by 50-100mg/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 DKA
 
====Long-Acting (Basal) Insulin====
*Two main practices exist: 1) Close the anion gap, then start basal insulin 2-3 hours before stopping insulin infusion, 2) Early basal insulin
**Potential benefits of early basal insulin (glargine or detemir) include protecting against erroneously stopping insulin infusion prematurely and eliminating the 2-3 hour waiting period of starting basal insulin while on IV infusion
*Early basal insulin:<ref>Rao P, et al. Evaluation of Outcomes Following Hospital-Wide Implementation of a Subcutaneous Insulin Protocol for Diabetic Ketoacidosis. JAMA Netw Open. 2022;5(4):e226417. doi:10.1001/jamanetworkopen.2022.6417</ref>
**Glargine 0.30 U/kg SQ x 1<ref>Hsia E, Seggelke S, Gibbs J, et al. Subcutaneous administration of glargine to diabetic patients receiving insulin infusion prevents rebound hyperglycemia. J Clin Endocrinol Metab. 2012;97(9):3132-3137.</ref><ref>Doshi P, Potter A, De L, Banuelos R, Darger B, Chathampally Y. Prospective randomized trial of insulin glargine in acute management of diabetic ketoacidosis in the emergency department: a pilot study. Acad Emerg Med. 2015;22(6):657-662.</ref>, '''OR'''
**Determine total 24 hour home dose of basal insulin and deliver that q24 hours (e.g. patient's normal home dose of glargine)<ref>Rappaport S, Endicott J, Gilbert M, Farkas J, Clouser R, McMillian W. A Retrospective Study of Early vs Delayed Home Dose Basal Insulin in the Acute Management of Diabetic Ketoacidosis. J Endocr Soc. 2019;3(5):1079-1086.</ref>


==Treatment==
===Short-Acting [[Insulin]]===
*Volume then potassium then insulin
====Intravenous Regimen (Short-Acting)====
===Labs===
''Do not stop insulin infusion until AG normalized AND bicarb normalized, despite resolution of blood sugar. Aim of insulin regime is to correct the acidosis, not merely the hyperglycemia.''
*Glucose check Q1hr
*Initial infusion 0.1 to 0.14 units/kg/hr of insulin (or 0.05units/kg/hr per local protocol)
*Chem 10 Q4hr
**Fixed Rate Insulin Infusion has improved outcomes over Variable Rate <ref>Paranthaman, K & Srinivasan, B. Fixed Rate Insulin Infusion (FRII) vs Variable Rate Insulin Infusion (VRII) in Management of Patients with Diabetic Ketoacidosis (DKA). https://www.gavinpublishers.com/article/view/fixed-rate-insulin-infusion-frii-vs-variable-rate-insulin-infusion-vrii-in-management-of-patients-with-diabetic-ketoacidosis-dka</ref><ref>Evans, K. Diabetic ketoacidosis: update on management. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771342/</ref>
*Corrected Na:
*Maintain BS between 150 and 200mg/dL until resolution of acidosis
**Add 1.6 for each glucose of 100 >100
**May require IV fluids to be switched to Dextrose 10% when BS <150mg/dL
*Continue IV infusion for 2 hrs after subcutaneous insulin is begun
*Subcutaneous route (appropriate only for mild DKA and if able to eat and void urine; poor perfusion may hamper its absorption)


===Fluids===
====Subcutaneous Regimen (Short-Acting)====
*Most pts 3-6L depleted
''A subcutaneous (SC) regimen must use short acting insulin and follow either a 1hr or 2hr dosing protocol. Regular insulin is not effective.<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>'' '''For patients who are euglycemic (glucose <250 mg/dl) at presentation (e.g. with mild gap), using standard [[Insulin#Insulin_Sliding_Scale|insulin sliding scale]] instead of this regimen.<ref>Rao P, et al. Evaluation of Outcomes Following Hospital-Wide Implementation of a Subcutaneous Insulin Protocol for Diabetic Ketoacidosis. JAMA Netw Open. 2022;5(4):e226417. doi:10.1001/jamanetworkopen.2022.6417</ref>''' <ref>Griffey R. et al. The SQuID protocol (subcutaneous insulin in diabetic ketoacidosis): Impacts on ED operational metrics. https://pubmed.ncbi.nlm.nih.gov/36775281/</ref>
*If severe hypovolemia: 1L NS/hr for up to 3 hr
*If mild dehydration then evaluate corrected Na+
**If hypernatremic: 1/2NS @ 250-500ml/hr
**If hyponatremic: NS @ 250-500ml/hr
*When BS < 250 switch to D51/2NS@ 150-200 ml/hr(+/- KCl)
*Bolus NS as needed for unstable VS


===Insulin===
'''1hr Protocol'''
*Check K prior to insulin Tx!
*Initial dose SC short acting insulin (e.g. Aspart): 0.3 units/kg [[ideal body weight]], followed by
**If K < 3.3 do not administer insulin
**0.1 units/kg SC every hour
*IV Route
**When blood glucose <250mg/dl (13.8 mmol/l), change IV fluids to D5<sub 0.45%</sub>NS and reduce SC aspart insulin to 0.05 units/kg/hr
**IV gtt 0.1 U/kg/hr
**Keep glucose at 150mg/dl (11 mmol/l) until resolution of DKA.
***Bolus dose unnecessary
**If BS does not decrease by 50-70/hr then double infusion rate qhr until achieved
***Refractoriness often due to infection
**When BS <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 50-70/hr then double dose qhr until achieved


===Potassium===
'''2hr Protocol'''
*Ensure adequate urine output before giving K
*Initial dose SC short acting insulin (e.g. Aspart): 0.3 units/kg [[ideal body weight]], followed by
*Prevent hypokalemia
**0.2 units/kg SC 1 hour later followed by Q2hr dosing
*>5.5: don't give, but recheck q2hr
**When blood glucose <250mg/dl (13.8 mmol/l), change IV fluids to D5 0.45% saline and reduce SC insulin to 0.1 units/kg/ 2hr
*3.3-5.5: give 30 meq/hr in each liter bag
**Keep glucose at 150mg/dl (11 mmol/l) until resolution of DKA.
**1/2NS is preferred b/c adding 30meq to NS = hypertonic soln
*<3.3: hold insulin and give 30 meq/hr until K >3.3


===Bicarb===
===[[Bicarbonate]]<ref>[[EBQ:Sodium Bicarbonate use in DKA]]</ref>===
*Consider for pH <6.9 AND:
{{EBQ Sodium Bicarbonate use in DKA conclusion}}
**Decreased contractility
*Pitfalls of sodium bicarbonate therapy in DKA (outside of last ditch efforts in severe acidemia)<ref>Nickson C. Sodium Bicarbonate and Diabetic Ketoacidosis. Jan 28, 2014. http://lifeinthefastlane.com/ccc/sodium-bicarbonate-and-diabetic-ketoacidosis/.</ref>
**Hypotension
**Paradoxical CSF acidosis
**Severe hyperkalemia
**Hypokalemia from H+ and K+ shifts
**Coma
**Large sodium bolus
*100 meq NaHCO3 in 400mL H2O @ 200 mL/hr
**Cerebral edema
**Dose as needed until pH > 7.00
**Shifts oxygen-hemoglobin dissociation curve to left, decreasing O2 delivery to tissues


===Phosphate===
===Subsequent Management===
*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 Q2r (then move to Q4hr)  
**Phosphate <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


==Complications==
====Sliding Scale====
*Cerebral Edema
*[[Insulin]] Sliding Scale to be started once patient's DKA has resolved and eating a full diet.
**Almost all affected pts are <20yr
**Associated with initial bicarb level; not rate of glucose drop
**Premonitory symptoms:
***Headache
***Incontinence
***Mental status change / seizure
**Treatment
***Mannitol IV 1-2gm/kg OR
***3% NS 5-10mL/kg over 30min
*Noncardiogenic pulmonary edema


===Sliding Scale===
===[[Intubation]]===
*200-250 = 4u sq
*Avoid intubation unless patient cannot generate respiratory alkalosis compensation due to extreme fatigue<ref>Four DKA Pearls. May 7, 2014. http://www.pulmcrit.org/2014/05/four-dka-pearls.html</ref>
*251-300 = 6
*Risks associated with intubation in DKA:
*301-350 = 8
**During sedation/paralysis, a rise in PaCO2 can decrease pH considerably
*351-400 = 10
**Severe gastroparesis in DKA creates a significant risk for aspiration
**Strong DKA patients generally can achieve greater hyperventilation than mechanical ventilated patients
*See [[Intubation#Severe_Metabolic_Acidosis|Intubation]] for more information


==Treatment Algorithm==
==Disposition==
[[File:ADA_DKA.gif]]
*Admit to higher level care (usually ICU or step-down unit initially)
*Subsequent hospital discharge requires closing on anion gap and resolution of symptoms.
*Patients with mild DKA may be treated as outpatients if reliable, close follow-up available and underlying causes not requiring admission
 
==Complications==
*[[Cerebral Edema in DKA]]


==See Also==
==See Also==
*[[Diabetes (Main)]]
*[[Diabetes mellitus (main)]]
*[[DKA (Peds)]]
*[[EBQ:Sodium_Bicarbonate_use_in_DKA|Evidence Review Sodium Bicarbonate in DKA]]
*[[Diabetic ketoacidosis (peds)]]
*[[Ketonemia]]
*[[Cerebral edema in DKA]]
 
==External Links==
*[http://www.bsped.org.uk/clinical/docs/DKAcalculator.pdf British Society for Paediatric Endocrinology and Diabetes - Paediatric Diabetic Ketoacidosis]
*[http://ddxof.com/diabetic-ketoacidosis/ DDxOf: Management of DIabetic Ketoacidosis]


==Source==
==References==
Tintinalli's, UpToDate.
<references/>


Image: UpToDate
[[Category:Endocrinology]]
[[Category:Endo]]

Latest revision as of 21:51, 16 April 2025

This page is for adult patients. For pediatric patients, see: diabetic ketoacidosis (peds)

Background

  • Patients in DKA are almost always K+ depleted despite initially fairly normal K+.
    • This is due to extracellular shift of K+ due to acidosis as well as insulin infusion, which increases uptake of K+ intracellularly.

Epidemiology

  • Mortality rate approximately 2-5%[1]

Pathophysiology

Defining features include hyperglycemia (glucose > 200mg/dl), acidosis (pH < 7.3), and ketonemia

Hyperglycemia

  • Leads to osmotic diuresis and depletion of electrolytes including sodium, potassium, magnesium, calcium and phosphorus.
  • Further dehydration impairs glomerular filtration rate (GFR) and contributes to acute renal failure
  • Hypokalemia may inhibit insulin release

Acidosis

  • Due to insulin deficiency -> lipolysis / accumulation of of ketoacids (represented by increased anion gap)
  • Compensatory respiratory alkalosis (i.e. tachypnea and hyperpnea - Kussmaul breathing)
  • Breakdown of adipose creates first acetoacetate leading to conversion to beta-hydroxybutyrate

Dehydration

  • Causes activation of RAAS in addition to the osmotic diuresis
  • The initial serum values for electrolytes such as K+ may be higher than actual body stores
  • Cation loss (in exchange for chloride) worsens metabolic acidosis

Clinical Features

  • May be the initial presenting of an unrecognized T1DM patient
  • OR symptoms/signs of inciting precipitant (e.g. history of med/dietary nonadherence, signs/symptoms of infection)
  • Presenting features may include:

Differential Diagnosis

Causes of DKA

Hyperglycemia

Evaluation

Workup

Workup to confirm diagnosis and search for possible inciting causes (e.g. infection, ACS)

Diagnosis

Diagnosis is made based on the presence of acidosis (e.g. venous pH < 7.3 or HCO3 <18) and ketonemia (e.g. >3mmol/L BOH or ketonuria) in the setting of diabetes (e.g. glucose >200mg/dl) [2]

Basic Laboratory Findings

  • Blood Glucose
    • Capillary blood sugar >200mg/dL
    • Blood sugar may not be very elevated if there is impaired gluconeogenesis (eg liver failure, severe alcoholism) or patient is taking a SGLT-2 Inhibitor [3]
  • Elevated Anion Gap
    • Bicarb may be normal due to compensatory and contraction alkalosis so the elevated anion gap or ketonuria may be the only clues to the DKA
  • Serum ketones
    • Beta hydroxybutyrate will be elevated

Blood Gas

No need to perform Arterial blood gas. Venous blood gas is sufficient[4]

  • Difference in pH from VBG vs ABG will be ±0.02pH units[5][6] [7][8]

Urinary analysis (ketonuria)

  • Urinalysis may be a useful screening test early in DKA, if serum ketones not available
    • However, may give a false negative for ketones later in DKA, as acetoacetate is converted to beta-hydroxybutyrate the urinary ketones may turn negative[9]

End Tidal CO2

Strongly consider capnography for respiratory distress[10]

  • ETCO2 can be used for bedside assessment of DKA in pts with glucose>550[11]
    • An ETCO2 of ≥35 is 100% sensitive to rule out DKA
    • An ETCO2 of ≤21 is 100% specific to diagnosis DKA

Management

Algorithm for the management of diabetic ketoacidosis
  • If the patient has an insulin pump, make sure it is shut off or disconnected

Volume Repletion

  • Administer 20-30cc/kg lactated ringers bolus during the first hour
    • Most important step in treatment since osmotic diuresis is the major driving force[7]
    • Most adult patients are 3-6L depleted
    • Increased systemic perfusion may transport insulin to previously unreached receptor sites, inhibiting ketogenesis
    • Increased renal perfusion promotes renal hydrogen ion loss
    • Use of LRs is preferred over NS [12],[13]
    • When blood sugar(BS) < 250-300 add a D10 infusion at an equal rate to the LR using a single IV line [14]
    • Patients can eat and drink if mental status is intact [15]

Electrolyte Repletion

  • Potassium (most important!)[16]
    • <3.5mEq/L:
      • Start potassium repleation: 20-30 mEq KCl to IVF/hr
      • Do not administer insulin (to avoid worsening of hypokalemia)
    • >3.5mEq/L and <5.5 mEq/L:
      • Start potassium repleation: 20-30 mEq KCl to IVF/hr
      • May start insulin (see below)
    • >5.5 mEq/L:
      • Hold potassium repletion and recheck electroltyes after initiaton of insulin (see below)
  • Sodium
    • Hyponatremia
      • Correct for hyperglycemia
        • Na+ decreases by 1.6mEq/L for every 100mg/dL increase in glucose (ie pseudohyponatremia)
      • If truly hyponatraemic, start NS 250-500ml/hr
    • Hypernatremia
      • Consider Lactated Ringers
  • Hypophosphatemia
    • <1.0 mEq/L, start repletion:
      • IV K2PO4 at 1mL/hour (contains 4.4meqK+ & 93mg phos)
      • Severe hypophosphatemia can cause cardiac and respiratory dysfunction
  • Hypomagnesemia
    • Mg<2.0mg/DL, start repletion:
      • 2g MgSO4 IV over 1h

Insulin Overview

  • Check potassium prior to insulin treatment (see above)! Do not administer insulin until potassium supplementation is underway.[17]
  • A bolus dose is unnecessary and may contribute to increased hypoglycemic episodes[18]
  • If the patient comes in wearing an insulin pump, turn off the pump and remove the subcutaneous catheter.
  • Expect BS to fall by 50-100mg/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 DKA

Long-Acting (Basal) Insulin

  • Two main practices exist: 1) Close the anion gap, then start basal insulin 2-3 hours before stopping insulin infusion, 2) Early basal insulin
    • Potential benefits of early basal insulin (glargine or detemir) include protecting against erroneously stopping insulin infusion prematurely and eliminating the 2-3 hour waiting period of starting basal insulin while on IV infusion
  • Early basal insulin:[19]
    • Glargine 0.30 U/kg SQ x 1[20][21], OR
    • Determine total 24 hour home dose of basal insulin and deliver that q24 hours (e.g. patient's normal home dose of glargine)[22]

Short-Acting Insulin

Intravenous Regimen (Short-Acting)

Do not stop insulin infusion until AG normalized AND bicarb normalized, despite resolution of blood sugar. Aim of insulin regime is to correct the acidosis, not merely the hyperglycemia.

  • Initial infusion 0.1 to 0.14 units/kg/hr of insulin (or 0.05units/kg/hr per local protocol)
    • Fixed Rate Insulin Infusion has improved outcomes over Variable Rate [23][24]
  • Maintain BS between 150 and 200mg/dL until resolution of acidosis
    • May require IV fluids to be switched to Dextrose 10% when BS <150mg/dL
  • Continue IV infusion for 2 hrs after subcutaneous insulin is begun
  • Subcutaneous route (appropriate only for mild DKA and if able to eat and void urine; poor perfusion may hamper its absorption)

Subcutaneous Regimen (Short-Acting)

A subcutaneous (SC) regimen must use short acting insulin and follow either a 1hr or 2hr dosing protocol. Regular insulin is not effective.[25] For patients who are euglycemic (glucose <250 mg/dl) at presentation (e.g. with mild gap), using standard insulin sliding scale instead of this regimen.[26] [27]

1hr Protocol

  • Initial dose SC short acting insulin (e.g. Aspart): 0.3 units/kg ideal body weight, followed by
    • 0.1 units/kg SC every hour
    • When blood glucose <250mg/dl (13.8 mmol/l), change IV fluids to D5<sub 0.45%NS and reduce SC aspart insulin to 0.05 units/kg/hr
    • Keep glucose at 150mg/dl (11 mmol/l) until resolution of DKA.

2hr Protocol

  • Initial dose SC short acting insulin (e.g. Aspart): 0.3 units/kg ideal body weight, followed by
    • 0.2 units/kg SC 1 hour later followed by Q2hr dosing
    • When blood glucose <250mg/dl (13.8 mmol/l), change IV fluids to D5 0.45% saline and reduce SC insulin to 0.1 units/kg/ 2hr
    • Keep glucose at 150mg/dl (11 mmol/l) until resolution of DKA.

Bicarbonate[28]

  • No evidence supports the use of sodium bicarb in DKA, with a pH >6.9
  • However, no studies have been performed for patients with pH <6.9 and the most recent ADA guidelines recommend it for patients with pH <7.1
  • Pitfalls of sodium bicarbonate therapy in DKA (outside of last ditch efforts in severe acidemia)[29]
    • Paradoxical CSF acidosis
    • Hypokalemia from H+ and K+ shifts
    • Large sodium bolus
    • Cerebral edema
    • Shifts oxygen-hemoglobin dissociation curve to left, decreasing O2 delivery to tissues

Subsequent Management

Labs/Monitoring

  • Glucose check Q1hr
  • Chem 10 Q2r (then move to Q4hr)
  • Check pH PRN based on clinical status (eval respiratory compensation)
  • Check appropriateness of insulin dose Q1hr (see below)
  • Corrected Electrolytes

Sliding Scale

  • Insulin Sliding Scale to be started once patient's DKA has resolved and eating a full diet.

Intubation

  • Avoid intubation unless patient cannot generate respiratory alkalosis compensation due to extreme fatigue[30]
  • Risks associated with intubation in DKA:
    • During sedation/paralysis, a rise in PaCO2 can decrease pH considerably
    • Severe gastroparesis in DKA creates a significant risk for aspiration
    • Strong DKA patients generally can achieve greater hyperventilation than mechanical ventilated patients
  • See Intubation for more information

Disposition

  • Admit to higher level care (usually ICU or step-down unit initially)
  • Subsequent hospital discharge requires closing on anion gap and resolution of symptoms.
  • Patients with mild DKA may be treated as outpatients if reliable, close follow-up available and underlying causes not requiring admission

Complications

See Also

External Links

References

  1. ↑ Lebovitz HE: Diabetic ketoacidosis. Lancet 1995; 345: 767-772.
  2. ↑ Glaser N, Fritsch M, Priyambada L, et al. ISPAD clinical practice consensus guidelines 2022: Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes 2022; 23:835.
  3. ↑ Peters AL et al. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care 2015 Sep; 38(9): 1687-1693.
  4. ↑ Ma OJ, Rush MD, Godfrey MM, Gaddis G. Arterial blood gas results rarely influence emergency physician management of patients
  5. ↑ Kelly AM et al. Review Article – Can Venous Blood Gas Analysis Replace Arterial in Emergency Medical Care. Emery Med Australas 2010; 22: 493 – 498.
  6. ↑ Ma OJ et al. Arterial Blood Gas Results Rarely Influence Emergency Physician Management of Patients with Suspected Diabetic Ketoacidosis. Acad Emerg Med Aug 2003; 10(8): 836 – 41.
  7. ↑ 7.0 7.1 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.
  8. ↑ Gokel Y, et al. 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.
  9. ↑ Stojanovic, V. Sherri Ihle. Role of beta-hydroxybutyric acid in diabetic ketoacidosis: A review. Can Vet J. 2011 Apr; 52(4): 426–430.
  10. ↑ Nagler J et al. Capnography: A valuable tool for airway management. Emerg Med Clin North Am, 26(4):881, Nov 2008.
  11. ↑ Chebl BR, Madden B, Belsky J, et al. Diagnostic value of end tidal capnography in patients with hyperglycemia in the emergency department. BCM Emerg Med. 2016; 16 (1).
  12. ↑ Carrillo et al. Balanced Crystalloid Versus Normal Saline as Resuscitative Fluid in Diabetic Ketoacidosis. https://pubmed.ncbi.nlm.nih.gov/34986659/
  13. ↑ Self et al. Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis: A Subgroup Analysis of Cluster Randomized Clinical Trials. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2772993/
  14. ↑ https://emcrit.org/ibcc/dka/
  15. ↑ Lipatov, K. et al. Early vs late oral nutrition in patients with diabetic ketoacidosis admitted to a medical intensive care unit. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347656/
  16. ↑ *http://emupdates.com/2010/07/15/correction-of-critical-hypokalemia/
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ Rao P, et al. Evaluation of Outcomes Following Hospital-Wide Implementation of a Subcutaneous Insulin Protocol for Diabetic Ketoacidosis. JAMA Netw Open. 2022;5(4):e226417. doi:10.1001/jamanetworkopen.2022.6417
  20. ↑ Hsia E, Seggelke S, Gibbs J, et al. Subcutaneous administration of glargine to diabetic patients receiving insulin infusion prevents rebound hyperglycemia. J Clin Endocrinol Metab. 2012;97(9):3132-3137.
  21. ↑ Doshi P, Potter A, De L, Banuelos R, Darger B, Chathampally Y. Prospective randomized trial of insulin glargine in acute management of diabetic ketoacidosis in the emergency department: a pilot study. Acad Emerg Med. 2015;22(6):657-662.
  22. ↑ Rappaport S, Endicott J, Gilbert M, Farkas J, Clouser R, McMillian W. A Retrospective Study of Early vs Delayed Home Dose Basal Insulin in the Acute Management of Diabetic Ketoacidosis. J Endocr Soc. 2019;3(5):1079-1086.
  23. ↑ Paranthaman, K & Srinivasan, B. Fixed Rate Insulin Infusion (FRII) vs Variable Rate Insulin Infusion (VRII) in Management of Patients with Diabetic Ketoacidosis (DKA). https://www.gavinpublishers.com/article/view/fixed-rate-insulin-infusion-frii-vs-variable-rate-insulin-infusion-vrii-in-management-of-patients-with-diabetic-ketoacidosis-dka
  24. ↑ Evans, K. Diabetic ketoacidosis: update on management. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771342/
  25. ↑ 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]
  26. ↑ Rao P, et al. Evaluation of Outcomes Following Hospital-Wide Implementation of a Subcutaneous Insulin Protocol for Diabetic Ketoacidosis. JAMA Netw Open. 2022;5(4):e226417. doi:10.1001/jamanetworkopen.2022.6417
  27. ↑ Griffey R. et al. The SQuID protocol (subcutaneous insulin in diabetic ketoacidosis): Impacts on ED operational metrics. https://pubmed.ncbi.nlm.nih.gov/36775281/
  28. ↑ EBQ:Sodium Bicarbonate use in DKA
  29. ↑ Nickson C. Sodium Bicarbonate and Diabetic Ketoacidosis. Jan 28, 2014. http://lifeinthefastlane.com/ccc/sodium-bicarbonate-and-diabetic-ketoacidosis/.
  30. ↑ Four DKA Pearls. May 7, 2014. http://www.pulmcrit.org/2014/05/four-dka-pearls.html
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