View source for Diabetic ketoacidosis

==Background==
*{{AdultPage|diabetic ketoacidosis (peds)}}


*Diabetic ketoacidosis (DKA) is a life-threatening hyperglycemic emergency characterized by '''hyperglycemia''' (or euglycemia in ~10%), '''metabolic acidosis''', and '''ketonemia'''
*Hospital admissions for DKA have increased substantially over the past decade<ref name="ADA2024">Umpierrez GE, Davis GM, ElSayed NA, et al. Hyperglycemic Crises in Adults With Diabetes: A Consensus Report. Diabetes Care. 2024;47(8):1257-1275.</ref>
*Patients in DKA are almost always K⁺ depleted despite initially normal or elevated serum K⁺
**Extracellular shift of K⁺ occurs due to acidosis, hyperosmolality, and insulin deficiency
**Insulin infusion drives K⁺ back intracellularly → can unmask severe total body K⁺ depletion

===Epidemiology===
*Inpatient DKA mortality: approximately 0.2% in type 1 diabetes and 1.0% in type 2 diabetes<ref name="ADA2024"/>
*DKA can occur in both type 1 and type 2 diabetes (up to 50% of DKA admissions are T2D in some series)
*~6-21% of adults with T1D present with DKA as their initial diagnosis<ref name="ADA2024"/>
*Recurrent DKA is common and often driven by insulin omission due to cost, mental health, substance use, or social determinants — the ED is an opportunity to screen and connect to resources<ref name="ADA2024"/>

===Pathophysiology===
''Defining features include hyperglycemia (glucose >200 mg/dL, or any glucose in a patient with known diabetes), acidosis (pH <7.3 or HCO₃ <18), and ketonemia (BHB ≥3 mmol/L)''<ref name="ADA2024"/>

====[[Hyperglycemia]]====
*Leads to osmotic diuresis and depletion of electrolytes including sodium, potassium, magnesium, calcium, and phosphorus
*Further dehydration impairs GFR and contributes to [[acute kidney injury]]
*Hypokalemia may inhibit insulin release
*Euglycemic DKA (~10% of cases): glucose <200 mg/dL with metabolic acidosis and ketonemia — seen with [[SGLT-2 inhibitors]], pregnancy, low carbohydrate intake, fasting, or recent insulin use<ref name="Peters2015">Peters AL et al. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care. 2015;38(9):1687-1693.</ref>

====[[Acidosis]]====
*Due to insulin deficiency → lipolysis → accumulation of ketoacids (represented by increased anion gap)
*Compensatory respiratory alkalosis (tachypnea/hyperpnea — Kussmaul breathing)
*Breakdown of adipose creates first acetoacetate, then conversion to beta-hydroxybutyrate (the predominant ketone in DKA)

====[[Dehydration]]====
*Causes activation of RAAS in addition to osmotic diuresis
*Average fluid deficit: 3-6 liters in adults (100 mL/kg)
*Initial serum values for electrolytes (especially K⁺) may be higher than actual total body stores
*Cation loss (in exchange for chloride) worsens metabolic acidosis

==Clinical Features==
{{DKA clinical features}}

==Differential Diagnosis==
===Causes of DKA (Precipitants)===
''Search for a precipitant in every DKA patient — it changes management''

*Infection (most common precipitant worldwide, 14-58% of cases)<ref name="ADA2024"/>
*Insulin noncompliance/omission — most common in T1D; ask about cost, access, mental health, pump malfunction
*[[Acute coronary syndrome|Cardiac ischemia / MI]]
*[[CVA|Stroke]]
*[[Pancreatitis]]
*[[PE|Pulmonary embolism]]
*[[SGLT-2 inhibitors]] (euglycemic DKA)
*[[Pregnancy]] (higher risk of euglycemic DKA)
*[[Steroid]] use (new or dose escalation)
*[[Alcoholic Ketoacidosis|Alcohol use]]
*[[Toxicologic exposure]]
*[[Hyperthyroidism]] / [[thyroid storm]]
*[[GI Hemorrhage]]
*[[Renal Failure]]
*New-onset diabetes (DKA as initial presentation)
*Insulin pump malfunction (kink, disconnection, site infection, battery failure)
*Substance use (cocaine, methamphetamine)
*Trauma

{{Hyperglycemia DDX}}

==Evaluation==
===Workup===
''Workup to confirm diagnosis, assess severity, and search for precipitating cause (e.g., infection, [[ACS]])''
*BMP (glucose, BUN/Cr, Na⁺, K⁺, Cl⁻, HCO₃⁻, anion gap)
*Blood glucose (and bedside point-of-care glucose)
*Beta-hydroxybutyrate (BHB) — preferred ketone marker for diagnosis, severity assessment, and monitoring resolution; ideally point-of-care<ref name="ADA2024"/>
*[[VBG]] (arterial blood gas is rarely needed)
*Magnesium, phosphorus, calcium
*CBC (leukocytosis is common in DKA even without infection — >25,000 or left shift more suggestive of infection)
*[[ECG]] — evaluate for [[hyperkalemia]]/[[hypokalemia]], ischemia, arrhythmia
*[[Urinalysis]] — ketonuria may be a useful screen but serum BHB is preferred (see below)
*[[CXR]] — if infection suspected
*[[Blood cultures]] — if concern for sepsis or bacteremia
*Lipase — if concern for [[pancreatitis]]
*[[Lactate]] — if concern for sepsis or tissue hypoperfusion
*Troponin — if chest pain or concern for ACS (interpret with caution in CKD)
*Pregnancy test — in all women of childbearing age
*[[HbA1c]] — helpful in assessing chronic glycemic control and distinguishing new-onset T1D from poorly controlled known diabetes

===Diagnosis===
''Diagnosis is made based on the presence of acidosis AND ketonemia in the setting of diabetes''<ref name="ADA2024"/>

====2024 ADA/EASD Consensus Diagnostic Criteria====
{| class="wikitable"
|-
! Criterion !! Diagnostic Threshold
|-
| '''Glucose''' || >200 mg/dL (11.1 mmol/L) '''OR''' known history of diabetes (glucose cutoff removed for known diabetics)
|-
| '''pH''' || <7.3 (venous)
|-
| '''Bicarbonate''' || <18 mEq/L
|-
| '''Beta-hydroxybutyrate''' || ≥3.0 mmol/L (preferred), or significant ketonuria if BHB unavailable
|}

====Severity Classification====
{| class="wikitable"
|-
! !! '''Mild''' !! '''Moderate''' !! '''Severe'''
|-
| '''pH''' || 7.25-7.30 || 7.00-7.24 || <7.00
|-
| '''Bicarbonate''' || 15-18 mEq/L || 10-14.9 mEq/L || <10 mEq/L
|-
| '''BHB''' || 3.0-5.9 mmol/L || 6.0-9.9 mmol/L || ≥10.0 mmol/L
|-
| '''Mental status''' || Alert || Alert/drowsy || Stupor/coma
|}

====Key Laboratory Pearls====
*Blood Gas: VBG is sufficient — pH difference from ABG is ±0.02 units<ref>Kelly AM et al. Review Article – Can Venous Blood Gas Analysis Replace Arterial in Emergency Medical Care. Emerg 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. 2003;10(8):836-41.</ref>
*Urinary ketones: May give a false negative later in DKA — the urine dipstick detects acetoacetate, not beta-hydroxybutyrate. As DKA worsens, the ratio shifts toward BHB, so urine ketones may paradoxically appear negative in severe DKA<ref>Stojanovic V, Ihle S. Role of beta-hydroxybutyric acid in diabetic ketoacidosis: A review. Can Vet J. 2011;52(4):426-430.</ref>
*Bicarb may be normal despite DKA due to compensatory/contraction alkalosis — the elevated anion gap or BHB may be the only clues
*Corrected sodium: Na⁺ decreases by ~1.6 mEq/L for every 100 mg/dL increase in glucose above 100 (some use 2.4 mEq/L per 100 mg/dL for glucose >400). The corrected sodium should rise as glucose falls during treatment — if it is falling, suspect excessive free water administration (risk of cerebral edema)
*ETCO₂: An ETCO₂ ≥35 mmHg is 100% sensitive to rule out DKA; an ETCO₂ ≤21 mmHg is 100% specific for DKA in patients with glucose >550<ref>Chebl RB, Madden B, Belsky J, et al. Diagnostic value of end tidal capnography in patients with hyperglycemia in the emergency department. BMC Emerg Med. 2016;16(1).</ref>
*Leukocytosis is common in DKA even without infection (stress response); WBC >25,000 or bandemia is more suggestive of true infection

==Management==
[[File:DKA management.png|thumb|Algorithm for the management of diabetic ketoacidosis]]
*If the patient has an insulin pump, shut it off and remove the subcutaneous catheter

===Volume Repletion===
*Administer 15-20 mL/kg/h isotonic crystalloid during the first hour (typically 1-1.5L)<ref name="ADA2024"/>
**Most important step in treatment since osmotic diuresis is the major driving force
**Most adult patients are 3-6L depleted; aim to correct ~50% of fluid deficit in first 8-12 hours
**[[Lactated Ringers]] is preferred over NS — may resolve DKA faster and causes less hyperchloremic acidosis<ref>Self WH, et al. Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis. JAMA Netw Open. 2020;3(11):e2024982.</ref><ref>Carrillo R, et al. Balanced Crystalloid Versus Normal Saline as Resuscitative Fluid in Diabetic Ketoacidosis. Am J Emerg Med. 2022;53:180-186.</ref>
**When blood glucose (BG) <250-300 mg/dL → add a D10 infusion at an equal rate to LR to prevent hypoglycemia while continuing insulin to clear ketones<ref>Farkas J. DKA. Internet Book of Critical Care (IBCC). 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. World J Diabetes. 2019;10(1):57-64.</ref>
*Use caution in patients with [[CHF]], [[chronic kidney disease]], or ESRD — smaller boluses with frequent reassessment

===[[Electrolyte Repletion]]===
====Potassium (Most Important!)====
*'''Check K⁺ BEFORE starting insulin. Do not give insulin until K⁺ supplementation is underway if K⁺ <3.5'''<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>
{| class="wikitable"
|-
! K⁺ Level !! Action
|-
| '''<3.5 mEq/L''' || '''Hold insulin.''' Start aggressive K⁺ repletion: 20-40 mEq KCl/hr IV. Recheck q1-2h. Start insulin only after K⁺ ≥3.5.
|-
| '''3.5-5.5 mEq/L''' || Start K⁺ repletion: 20-30 mEq KCl per liter of IVF. May start insulin concurrently.
|-
| '''>5.5 mEq/L''' || Hold K⁺ repletion. Start insulin. Recheck K⁺ in 1-2 hours (it will fall rapidly with insulin + fluids).
|}

====Other Electrolytes====
*Sodium: Calculate corrected Na⁺ (see above). If truly hyponatremic, use NS. If hypernatremic, consider LR or half-NS.
*[[Hypophosphatemia]]: Replete if <1.0 mg/dL (IV K₂PO₄ — has the added benefit of providing K⁺). Severe hypophosphatemia can cause cardiac/respiratory dysfunction and hemolytic anemia.
*[[Hypomagnesemia]]: Replete if Mg <2.0 mg/dL (2g MgSO₄ IV over 1 hour)

===[[Insulin]] Overview===
*A bolus dose is NOT recommended — no benefit and may increase hypoglycemic episodes<ref>Goyal N, et al. Utility of Initial Bolus Insulin in the Treatment of Diabetic Ketoacidosis. J Emerg Med. 2010;38(4):422-7.</ref>
*Expect BG to fall by 50-100 mg/dL per hour with adequate insulin and fluids
*Refractory hyperglycemia → consider unrecognized infection, inadequate fluid resuscitation, or insulin delivery failure

====Intravenous Insulin (Standard for Moderate-Severe DKA)====
*Fixed rate: 0.1 units/kg/hr (or 0.14 units/kg/hr without bolus; or 0.05 units/kg/hr per some protocols)<ref name="ADA2024"/>
**Fixed rate infusion has improved outcomes over variable rate<ref>Evans K. Diabetic ketoacidosis: update on management. Clin Med (Lond). 2019;19(5):396-398.</ref>
*'''Do NOT stop insulin infusion until DKA has resolved''' — resolution requires clearance of ketones, not merely correction of glucose
*Resolution criteria (2024 consensus):<ref name="ADA2024"/>
**BHB <0.6 mmol/L (preferred), AND
**Venous pH >7.3, AND
**Bicarbonate ≥18 mEq/L
**If BHB is not available, normalization of anion gap is an acceptable surrogate
*When BG <250-300 mg/dL → add D10 infusion; do NOT decrease insulin below 0.05 units/kg/hr until ketones clear
*Maintain BG between 150-250 mg/dL until resolution of acidosis

====Subcutaneous Insulin (Appropriate for Mild DKA Only)====
''SC regimen requires rapid-acting insulin (e.g., aspart, lispro). Appropriate only for mild DKA (pH 7.25-7.3, alert, tolerating PO, able to void). Poor perfusion may impair absorption.''<ref name="ADA2024"/><ref>Umpierrez G, et al. Treatment of diabetic ketoacidosis with subcutaneous insulin aspart. Diabetes Care. 2004;27(8):1873-8.</ref><ref>Griffey R, et al. The SQuID protocol (subcutaneous insulin in diabetic ketoacidosis): Impacts on ED operational metrics. Am J Emerg Med. 2023;66:14-18.</ref>

1-Hour Protocol:
*Initial: 0.3 units/kg SC, then 0.1 units/kg SC every hour
*When BG <250: add D5 0.45% NS; reduce to 0.05 units/kg/hr SC
*Target BG ~150 mg/dL until DKA resolution

2-Hour Protocol:
*Initial: 0.3 units/kg SC, then 0.2 units/kg SC at 1 hour, then 0.2 units/kg SC q2hr
*When BG <250: add D5 0.45% NS; reduce to 0.1 units/kg q2hr SC
*Target BG ~150 mg/dL until DKA resolution

====Transition to Basal-Bolus Insulin====
*Start basal insulin (glargine) 1-2 hours BEFORE discontinuing IV insulin infusion<ref name="ADA2024"/>
*Two approaches:
**Early basal: Glargine 0.3 U/kg SC ×1 early in DKA course (protects against rebound hyperglycemia, eliminates the 1-2h overlap waiting period)<ref>Hsia E, et al. Subcutaneous administration of glargine to diabetic patients receiving insulin infusion prevents rebound hyperglycemia. J Clin Endocrinol Metab. 2012;97(9):3132-7.</ref><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.</ref>
**Traditional: Close the anion gap / clear BHB → start basal insulin 1-2h before stopping infusion → verify patient is eating before fully transitioning

===[[Bicarbonate]]===
{{EBQ Sodium Bicarbonate use in DKA conclusion}}
*Generally NOT recommended — multiple studies show no benefit in DKA resolution or time to discharge<ref name="ADA2024"/>
*Consider only if pH <6.9 (or <7.0 per some protocols) with hemodynamic instability
*Pitfalls of bicarbonate in DKA:<ref>Nickson C. Sodium Bicarbonate and Diabetic Ketoacidosis. Life in the Fast Lane. 2014.</ref>
**Paradoxical CSF acidosis
**Hypokalemia from H⁺/K⁺ shifts
**Large sodium bolus
**Risk of cerebral edema
**Shifts oxygen-hemoglobin dissociation curve leftward → decreased O₂ delivery

===Additional Management Considerations===
*VTE prophylaxis: DKA is a hypercoagulable state — consider prophylactic-dose [[heparin]] or [[enoxaparin]] (adjust for renal function) in immobilized or critically ill patients
*Infection: Treat empirically if suspected; do not wait for culture results to initiate antibiotics
*Continuous telemetry: [[Hyperkalemia]] and [[hypokalemia]] are both arrhythmogenic; monitor throughout treatment

===Intubation===
*'''Avoid intubation in DKA whenever possible''' — this is a critical ED pearl<ref>Farkas J. Four DKA Pearls. PulmCrit. 2014.</ref>
*Risks:
**During sedation/paralysis, loss of compensatory hyperventilation → precipitous pH drop that can cause cardiac arrest
**Severe gastroparesis in DKA → high aspiration risk
**Awake DKA patients can generally achieve greater minute ventilation than a mechanical ventilator
*If intubation is unavoidable:
**Set the ventilator to '''match the patient's pre-intubation respiratory rate and tidal volume''' (high RR, high Vt)
**Avoid paralyzing the patient if possible
**Pre-oxygenate aggressively
*See [[Intubation#Severe Metabolic Acidosis|Intubation in severe metabolic acidosis]] for more detail

===Subsequent Monitoring===
*Glucose check Q1hr (bedside POC)
*BMP Q2hr initially (then Q4hr as improving); include anion gap calculation
*BHB Q2-4hr if available (preferred over anion gap for monitoring resolution)<ref name="ADA2024"/>
*Check VBG pH PRN based on clinical status
*Assess insulin dose adequacy Q1hr (BG should fall 50-100 mg/dL per hour)
*Monitor corrected sodium trend — should be rising as glucose falls
*K⁺ with every BMP — and whenever insulin rate is changed
*Sliding scale insulin to be started once DKA has fully resolved and patient is eating a full diet

==Disposition==
*Admit to ICU or step-down: Moderate-severe DKA (pH <7.24), AMS, hemodynamic instability, significant comorbidity, need for IV insulin infusion
*Admit to monitored bed: Mild DKA on SC protocol, but requiring observation for resolution and precipitant evaluation
*Consider ED treatment and discharge (rare): Only for mild DKA in a known, reliable patient with clear precipitant (e.g., insulin pump failure), DKA fully resolved before discharge (BHB <0.6 or anion gap closed, pH >7.3, bicarb ≥18, BG <200, tolerating PO, K⁺ normal), and close follow-up within 24-48 hours<ref name="ADA2024"/>
*Discharge education: Sick day rules (never stop basal insulin, check BG and ketones when ill, maintain hydration), when to seek care (persistent vomiting, BG >300, positive ketones), insulin access resources if cost is a barrier
*Schedule outpatient follow-up within 1-2 weeks if medications were changed (or within 1 month)<ref name="ADA2024"/>

==Complications==
*[[Cerebral Edema in DKA]]: More common in pediatric DKA; risk factors include excessive free water, rapid glucose correction, failure of corrected sodium to rise, and bicarbonate use
*[[Hypokalemia]]: Most dangerous iatrogenic complication — from insulin-driven intracellular K⁺ shift without adequate repletion
*Hypoglycemia: From excessive insulin without adequate dextrose supplementation
*[[ARDS]]/pulmonary edema: From aggressive fluid resuscitation, especially in patients with cardiac or renal comorbidities
*Venous thromboembolism: DKA is a prothrombotic state
*Rhabdomyolysis (rare)
*Dialysis disequilibrium-like syndrome (rapid osmolar shifts)


<div style="display:none">
<!-- SMW MedicationDose annotations for DKA medications -->
{{MedicationDose|drug=Insulin|dose=0.1 units/kg/hr IV infusion (no bolus); reduce to 0.02-0.05 units/kg/hr when BG <250|route=IV drip|context=IV insulin for moderate-severe DKA|indication=Diabetic ketoacidosis|notes=Do NOT stop until DKA resolved; no bolus recommended}}
{{MedicationDose|drug=Insulin|dose=0.3 units/kg SC initial, then 0.1-0.2 units/kg SC q1-2h|route=SC|context=SC insulin for mild DKA only|indication=Diabetic ketoacidosis|notes=Mild DKA only (pH 7.25-7.3, alert, tolerating PO); poor perfusion impairs absorption}}
{{MedicationDose|drug=Sodium bicarbonate|dose=100 mEq in 400 mL sterile water IV over 2 hours|route=IV drip|context=Severe acidosis (pH <6.9)|indication=Diabetic ketoacidosis|notes=Generally NOT recommended; consider only if pH <6.9 with hemodynamic instability}}
</div>
==See Also==
*[[Diabetes mellitus (main)]]
*[[EBQ:Sodium Bicarbonate use in DKA|Evidence Review: Sodium Bicarbonate in DKA]]
*[[Diabetic ketoacidosis (peds)]]
*[[Ketonemia]]
*[[Cerebral edema in DKA]]
*[[Hyperglycemia]]
*[[Hyperosmolar hyperglycemic state]]
*[[Alcoholic Ketoacidosis]]
*[[Chronic kidney disease]]

== Calculators ==
{{Corrected_Sodium_Calculator}}

{{Anion_Gap_Calculator}}

==External Links==
*[https://diabetesjournals.org/care/article/47/8/1257/156808/Hyperglycemic-Crises-in-Adults-With-Diabetes-A ADA 2024 Consensus Report: Hyperglycemic Crises in Adults (Full Text)]
*[https://emcrit.org/ibcc/dka/ IBCC - DKA Management]
*[http://ddxof.com/diabetic-ketoacidosis/ DDxOf: Management of Diabetic Ketoacidosis]

==References==
<references/>

[[Category:Endocrinology]]