This document discusses diabetic ketoacidosis (DKA), a life-threatening complication of diabetes caused by a lack of insulin. It provides details on the pathophysiology, presentation, diagnosis, and treatment of DKA. Treatment involves rapidly correcting dehydration and electrolyte abnormalities with intravenous fluids, replenishing potassium, and administering insulin to lower blood glucose levels and reverse ketosis. The main goals of treatment are to resuscitate the patient, replete fluids and electrolytes, and reverse the metabolic acidosis through insulin administration.

1. 1
Hyperglycemia
Metabolic
Acidosis
Ketosis
Background and Epidemiology
Pathophysiology: The culprit is insufficient insulin
DKA
Anna Sandler
PharmD Candidate, 2023
 Diabetic ketoacidosis (DKA): hyperglycemic
emergency characterized by severe alterations in
carbohydrate, protein, and lipid metabolism.
 Increasing hospitalization rates: > 220K admissions,
6.76 billion USD cost in 2017.
 Decreasing mortality: < 1%.
 Most often occurs in those with type I diabetes
(T1D) but can occur in type II diabetes (T2D).
 Hyperosmolar hyperglycemic State (HHS): Life-
threatening emergency with glucose elevations with
little to no ketosis.
 Insulin deficit
o Inadequate therapy
o Pancreatic insufficiency (T1D)
 Counter-regulatory hormones:
o Glucagon
o Cortisol
o Epinephrine
Precipitating events: Illness,
inadequate insulin, medications1
 Breakdown of glycogen, protein and
lipids provides substrates for glucose
production and ketone production.
Anion-gap
metabolic
acidosis
 Glycosuria
 Dehydration
 Impaired renal function
 Electrolyte abnormalities
1: Other provoking factors can include MI, pancreatitis, alcohol and illicit drug use. Medications that can precipitate DKA
include corticosteroids, thiazide diuretics, and SGLT-2 inhibitors. SGLT-2 inhibitors have been associated with euglycemic
diabetic ketoacidosis (EDKA). Although the mechanism is not entirely understood, SGLT-2 inhibitors increase urinary glucose
excretion, maintaining euglycemia but lead to decreased insulin secretion, ultimately promoting lipolysis and ketogenesis.
 Beta hydroxybutyrate
 Acetone
 Acetoacetate

2. 2
Mild Moderate Severe HHS
Plasma glucose (mg/dL) >250 >250 >250 > 600
Arterial pH 7.25-7.30 7.00-7.24 <7.00 > 7.30
Serum Bicarbonate
(mEq/L)
15-18 10-<15 <10 >18
Urine Ketones Pos. Pos. Pos. Small
Serum Ketones Pos. Pos. Pos. </= small
Anion gap >10 >12 >12 Variable
Mental status Alert Alert/drowsy Stupor/coma Stupor/coma
CBC With
differential2
ABGs
UA
Ketones CMP
EKG
Gluc-
ose
Diagnosis and Presentation: A starvation of cells
 Presentation: A starved state
 Increased thirst, urination, hunger
 Volume depletion: Decreased skin turgor, dry mucosa,
tachycardia, hypotension (severe)
 Fatigue, Weakness, alteration in mental status
 Signs of ketosis: Fruity breath odor
Treatment: General Overview
Severity of DKA is
INDEPENDENT of
glucose values!
ABGs: Arterial Blood Gases; CBC: Complete blood count; CMP: complete metabolic pan; EKG: electrocardiogram; UA: Urine
Analysis
2: Elevated white blood cell counts (10,000-15,000 mm3
) are common in DKA and can occur due to dehydration, stress and
movement of leukocytes away from the blood vessel walls.
Do not forget: Correct serum Na
and K extracellular shift
Electrolytes
Fluids
Insulin
 Treated as a medical emergency
 Key themes (The 3Rs): Resuscitate, Replete, Reverse the gap
SubQ
Insulin

3. 3
Agent Dose/Rate Pearls
NaCl  Hypovolemic shock:
infuse 0.9% NaCl as
quickly as possible
 Hypovolemia without
shock: 15-20 mL/kg
lean body weight/hour
for first couple of
hours
 Euvolemia: Rate
guided by clinical
assessment
 Monitor urine output, blood
pressure, and electrolytes
 As the patient stabilizes, the
rate can be lowered to 4-14
mL/kg/hour or 250-500
mL/hour
 Once corrected Na is normal (>
135 mEq/L), the solution can
be changed to 0.45% NaCl
K KCl dose
< 3.3 mEq/L  20-40 mEq/hour
 HOLD insulin
3.3-5.3 mEq/L  20-30 mEq added to each liter of IV
replacement fluid
> 5.3 mEq/L  Delay KCl until K < 5.3 mEq/L
Treatment: Fluids
Fluids
 Benefits
o Expand extracellular volume and help correct acidosis
o Increase insulin responsiveness
o Reduce stress hormone levels
 Agent of choice: 0.9% NaCl
o Lack of strong evidence in support of balanced crystalloids3
 Fluid composition dependent on electrolyte needs of the patient
Treatment: Electrolyte replenishment
 It is important to achieve goal K levels since insulin will lead to an intracellular shift of K
 Almost all DKA patients have a K deficit usually due to glucose osmotic diuresis.
 Goal: 4-5 mEq/L
 Agent: IV potassium chloride (KCl), added to replacement fluid
o Added to either isotonic or ½ NS depending on hydration, Na, and clinical assessment
of the patient
Electrolytes
3: A 2022 meta-analysis demonstrated that resuscitation with balanced crystalloids (e.g., Lactated Ringer’s) may result in
shorter time to DKA resolution and shorter hospital stay compared to saline. A 2021 cluster, crossover open-label,
randomized controlled phase 2 trial (SCOPE-DKA) conducted in seven Australian ICUs over 13 months revealed Plasmalyte-
148 may lead to faster metabolic acidosis resolution when compared to 0.9% NaCl. Additional subgroup analyses of
balanced crystalloids in ED and ICU patients also demonstrate potential benefits over saline.

4. 4
Blood glucose Insulin rate
>250 mg/dL  0.1 units/kg IV bolus followed by 0.1 units/kg/hour
 Alternative: 0.14 units/kg
200-250 mg/dL  0.02-0.05 units/kg/hr followed by dextrose-containing IV
fluids until resolution of DKA
Diagnosis SubQ Insulin regimen
Prior diagnosis  Resume outpatient dose
New diagnosis  Basel-bolus regimen (glargine/detemir/degludec-
lispro/aspart/glulisine)
 Initial dose: 0.5 units/kg/day
o Half basal, half bolus divided between meals
 Alternative: Insulin NPH
HCO3
>/= 15
Clinical
Stability
Resoln
pH >
7.3
PO
feeding
Anion
gap
</= 12
Transitioning to subcutaneous insulin
Treatment: Insulin and Dextrose
Insulin
 Agent: Insulin Regular (IV)
 Administered until anion gap is closed.
 Benefits: Reduces hepatic glucose production, inhibits ketogenesis and glucagon
secretion.
 Resolution of DKA: Glucose
< 200 mg/dL + any two of
the following on the left
 Start when DKA has resolved and the patient is able to tolerate oral feeding.
 Continue IV insulin infusion for 2 hours after starting subcutaneous insulin.
 Dose dependent on prior or new diagnosis of diabetes.
SubQ
Insulin

5. 5
Honorable mention: Sodium Bicarbonate
 Use controversial and lack of prospective randomized control
trials
 Patients who may benefit from cautious administration:
o arterial pH </= 6.9
 Dose: 100 mEq in 400 mL sterile water
administered over two hours
o Potentially life-threatening hyperkalemia
 Bicarbonate shifts K into cells
 Potential harmful effects:
o Post-metabolic alkalosis once metabolic acidosis is
resolved
 Metabolism of ketoacids generates
bicarbonate
o Reduction in hyper ventilatory drive leading to
increased CO2 diffusion into the brain and paradoxical
drop in cerebral pH
o
Recall, insulin is used
to reverse the
metabolic acidosis

6. 6
1. Self WH, Evans CS, Jenkins CA, et al. Clinical Effects of Balanced Crystalloids vs Saline in Adults With
Diabetic Ketoacidosis: A Subgroup Analysis of Cluster Randomized Clinical Trials. JAMA Netw Open.
2020;3(11):e2024596. doi:10.1001/jamanetworkopen.2020.24596
2. Emmett M, Hirsch IB. Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults:
Treatment. UpToDate. Published online March 24, 2022.
3. Westerberg DP. Diabetic ketoacidosis: evaluation and treatment. Am Fam Physician. 2013;87(5):337-
346.
4. Eledrisi MS, Elzouki AN. Management of Diabetic Ketoacidosis in Adults: A Narrative Review. Saudi J
Med Med Sci. 2020;8(3):165-173. doi:10.4103/sjmms.sjmms_478_19
5. Alghamdi NA, Major P, Chaudhuri D, et al. Saline Compared to Balanced Crystalloid in Patients With
Diabetic Ketoacidosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Critical Care Explorations. 2022;4(1):e0613. doi:10.1097/CCE.0000000000000613
6. Ramanan M, Attokaran A, Murray L, et al. Sodium chloride or Plasmalyte-148 evaluation in severe
diabetic ketoacidosis (SCOPE-DKA): a cluster, crossover, randomized, controlled trial. Intensive Care
Med. 2021;47(11):1248-1257. doi:10.1007/s00134-021-06480-5
Picture links
https://www.researchgate.net/figure/Pathogenesis-of-diabetic-ketoacidosis_fig1_341485181
https://www.pinterest.com/pin/6-symptoms-of-diabetic-ketoacidosis--201465783322879033/
http://clipart-library.com/closed-door-cliparts.html
https://www.diabetes.co.uk/insulin/diabetes-and-injecting-insulin.html
References

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