Diabetic

Ketoacidosis
Dr. Kaustuv De
Fellow (3rd yr.)
Critical care medicine
 Definition

 The biochemical criteria for the diagnosis of DKA:

 Hyperglycemia [ BG >11 mmol/L (≈ 200 mg/dL)]

 Venous pH < 7.3 or bicarbonate < 15 mmol/L (Metabolic acidosis)

 Ketonemia or ketonuria (Hyperketosis)

 Hyperosmolarity

 If available, β-hydroxybutyrate (BHOB) levels > 3 mmol/L is indicative of DKA

 Urine ketones are typically > 2+ (moderate or large) positive

 Severity

 Mild: venous pH < 7.3 or bicarbonate < 15 mmol/L

 Moderate: venous pH < 7.2 or bicarbonate < 10 mmol/L

 Severe: venous pH < 7.1 or bicarbonate < 5 mmol/L

 Precipitating factors

 Missed insulin common cause, particularly in adolescents

 Stress, via secretion of catecholamines, glucagon, and cortisol leads to glucose and ketoacid
production and can precipitate DKA - Hence, infection is commonly an inciting factor in DKA

 Medications such as corticosteroids and atypical antipsychotics can also precipitate DKA
Pathophysiology
Pathophysiology (Contd.)

 Deficiency of circulating Insulin

or Insulin resistance
 Increased counterregulatory
hormones : catecholamines,
glucagon, cortisol, and growth
hormone
 Accelerated catabolic state
 Increased glycogenolysis and
gluconeogenesis by liver and
kidney
 Increased lipolysis and
ketogenesis
 Pathophysiology (Contd.)

Increased glucose Increased lipolysis Hyperglycemia Stimulate further Lactic acidosis from
production and and ketogenesis together with stress hormone hypoperfusion or
simultaneous cause ketonemia and hyperketonemia production, which sepsis contributes to
impairment of metabolic acidosis cause osmotic induces more severe the acidosis
peripheral glucose diuresis, insulin resistance
utilization combine dehydration, and and worsening
to result in obligatory loss of hyperglycemia and
hyperglycemia an electrolytes hyperketonemia
hyperosmolality
Clinical presentation
 Symptoms
 Polyuria (due to glucose-induced osmotic diuresis) and Polydipsia (due to increased urinary water losses)
 Nocturia and enuresis
 Fatigue
 Weight loss
 Occasionally, vaginal or cutaneous moniliasis may occur
Most apparent in older children and adolescents

 Children with DKA typically present with anorexia, nausea, vomiting, and abdominal pain
 Polyphagia initially, however, once insulin deficiency becomes more severe and ketoacidosis develops,
appetite is suppressed
 Symptoms (Contd.)

In infants, the diagnosis is more difficult as polyuria may not be appreciated, and polydipsia is not
apparent
 Decreased energy and activity, irritability, weight loss, and physical signs of dehydration are
common findings
 In addition, severe Candida diaper rash should raise suspicion for diabetes
 Signs
 Rapid, shallow breathing initially, that, as the acidosis grows more severe, becomes slower,
deeper, and labored (Kussmaul breathing)
 In infants, hyperpnea may be manifested only by tachypnea
 Clinical signs of intravascular volume depletion such as tachycardia, poor peripheral perfusion,
and decreased skin turgor
 Less prominent due to osmotically maintained intravascular fluid volume and adequate urine
output due to osmotic diuresis
 One study looked at physician's ability to assess dehydration in DKA patients and found 70% of
patients were inaccurately assessed

Koves IH, Neutze J, Donath S, et al. The accuracy of clinical assessment of dehydration during diabetic ketoacidosis in childhood. Diabetes Care 2004; 27:2485
 Signs (Contd.)

 Neurologic findings ranging from drowsiness, lethargy, and obtundation to coma

 However, there is no direct correlation between the degree of acidosis, hyperglycemia, and the
disturbances in the level of consciousness
 Characteristic acetone (ketotic) breath odor
 Laboratory
abnormalities
 Laboratory abnormalities (Contd.)

Hyperglycemia
 Serum glucose concentrations > 200 mg/dL
 Glycosuria – high levels of serum glucose exceed the renal threshold – osmotic diuresis

Hyperosmolality
 Responsible for at least as much of the physiologic derangements seen in DKA as ketoacidosis
 Osmolality = 2[Na+] + [K+] + [Glucose]/18 + [BUN]/2.8
 In DKA both Glucose and BUN are elevated, presenting additional osmotic load
 Contributes to fluids shifts, maintained intravascular volumes at expense of interstitial and, in severe cases,
intracellular fluid – eventually lost volume in urine
 Laboratory abnormalities (Contd.)

Metabolic acidosis
 Elevated plasma ketoacids and lactic acid
 Ketoacids – acetoacetate and β-hydroxybutyrate (BHOB)
 Ketones normally stimulate insulin release and inhibit lipolysis – absence of this feedback loop – extreme lipemia
and ketonemia
 Lactic acid – from hypoxia and/or poor tissue perfusion
 Non-enzymatic decarboxylation of acetoacetate produce elevated acetone and CO 2 – acetone acts as buffer –
excreted in breath and urine
 Lactic acidosis shifts acetoacetate toward BHOB – reducing body’s ability to excrete ketoacids by acetone route
 BHOB to acetoacetate ratio is about 3:1 in DKA, can be as high as 15:1 in severe cases
 Laboratory abnormalities (Contd.)

 BHOB is a better indicator of metabolic

status than acetoacetate when detecting
and treating DKA
 Urine ketones are predominantly
acetoacetate
 Serum BHOB levels should be assessed
whenever possible
 Laboratory abnormalities (Contd.)

Sodium levels
 Hyponatremia is often reported in DKA – mostly artifact
 True Na+ levels need to be calculated
 Correction for glucose:
True [Na+] = Serum [Na+] + 1.6 [ {Serum Glucose -100}/100 ]
 Correction for lipemia:
True [Na+] = Serum [Na+] (0.021 [T] + 0.994), where T = serum Triglyceride in g/dL
 Laboratory abnormalities (Contd.)

Potassium levels
 Hyperkalemia is commonly found at presentation in DKA
 Due to redistribution of potassium from intracellular fluid to extracellular fluid caused by both
metabolic acidosis and hyperosmolality
 Continued osmotic diuresis subsequently causes progressive depletion of body potassium stores
 Best way to assess for intracellular potassium deficit is by looking for U-waves and flattened T-
waves on the EKG
 With Insulin replacement the potassium rapidly shifts back to the intracellular compartment,
potentially causing significant hypokalemia, with resultant risk of arrythmia
 Important to provide potassium during treatment of DKA
 Laboratory abnormalities (Contd.)

Hyperchloremia
 Hyperchloremic acidosis often coexists with increased anion gap metabolic acidosis
 Hyperchloremia often results from the high chloride load delivered during the fluid resuscitation
 Hypoperfusion of the kidneys due to hypovolemia can eventually cause chloride retention

Hypophosphatemia
 Profound hypophosphatemia is common at presentation due to renal losses from osmotic diuresis
 Can cause rhabdomyolysis, hemolysis, muscle weakness, respiratory failure and insulin resistance
 Laboratory abnormalities (Contd.)

Hypomagnesemia
 Hypomagnesemia is common
 Overly aggressive treatment of hypophosphatemia can depress levels of magnesium and calcium
 Can inhibit parathyroid hormone response to hypocalcemia

Hypocalcemia
 Hypocalcemia may be present, though, rarely requires correction
 iCal is usually normal
Complications
 Complications (contd.)

 Cerebral edema
 Pulmonary edema
 CNS hemorrhage or thrombosis
 Large vessel thromboses
 Cardiac arrythmias
 Pancreatitis
 Renal failure
 Intestinal necrosis
 Rhinocerebral mucormycosis
 Complications (contd.)

Cerebral edema
 Most frequent serious complication of DKA – approximately 1% of pediatric DKA
 Accounts for 57-87% of deaths in DKA
 However, studies examining ventricular size in asymptomatic DKA patients has demonstrated a 50% incidence of ventricular
narrowing suggesting a much higher incidence of subclinical cerebral edema
 Outcomes poor with 21-24% mortality and 21-26% permanent neurological morbidity
 Symptoms and signs include headache, altered mental status , hypertension, bradycardia, and other signs of increased intracranial
pressure
 Attributed to rapid changes in serum osmolality or overly vigorous fluid resuscitation during treatment of DKA
 More recent studies suggest the cerebral edema during DKA may be predominantly vasogenic and osmolar factors may play a less
important role
 In a multicenter RCT by Kuppermann et al and the PECARN network of 1255 children with DKA, there was no difference in
neurological outcomes based on sodium content (1/2 NS vs. NS) and rate of fluid resuscitation

Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis. Kuppermann et al N Engl J Med 2018;378:2275-87.
 Complications (contd.)

Cerebral edema
 Greater risk for cerebral edema include:
 higher BUN at presentation
 higher hypocapnia at presentation
 lesser rise in measured sodium concentration during treatment
 No pharmacological agent has clearly demonstrated effectiveness in DKA related cerebral edema
 Case reports of prompt treatment with Mannitol being beneficial
 One retrospective analysis showing increased associated mortality with use of hypertonic saline
has added to the controversy of hyposmolar agent of choice
• Glaser N, Barnett P, McCaslin I, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American
Academy of Pediatrics. N Engl J Med 2001; 344:264
• Decourcey DD, Steil GM, Wypij D, Agus MS. Increasing use of hypertonic saline over mannitol in the treatment of symptomatic cerebral edema in pediatric diabetic ketoacidosis: an 11-year
retrospective analysis of mortality. Pediatric Critical Care Medicine 2013;14(7)694-700
 Complications (contd.)

Cerebral edema
 Intubation of the DKA patient with cerebral edema has been associated with poorer outcomes
 Should be approached cautiously
 Patients will still be hyperventilating with PaCO 2 levels as low as 6 mmHg
 It is nearly impossible to hyperventilate a patient to that degree and hence, there exists a significant
risk of the PaCO2 rising, intracranial vessels dilating, ICP increasing, and potential herniation
 Nonetheless, if the patient is in extremis or beginning to exhibit CO 2 retention, careful
neuroprotective (premedication with lidocaine, avoiding use of ketamine and succinylcholine)
intubation may be required
 Complications (contd.)

 Thrombosis is common in DKA patients with one study demonstrating a 50% incidence of
venous thrombosis with femoral central venous access
 Hence, CVL's are generally not placed in DKA patients unless absolutely necessary

 Hypoglycemia can occur with insulin treatment and requires careful monitoring as well as
vigilance to ensure that the insulin/fluids/dextrose ordered is actually being given to the patient.
Management
 Fluid replenishment
 Initial treatment directed at restoring perfusion and hemodynamic stability
 Intravenous boluses with NS or other isotonic fluids (LR, normosol)
 This will drop the serum glucose and should help increase the patient's GFR
 Rarely needs more than the initial bolus with 20 ml/kg of fluid as intravascular volume is mostly
maintained
 Frequently, the serum glucose concentration will decrease substantially with rehydration alone
 Rest of the dehydration should be slowly corrected over 36-48 hrs
 Fluid correction should not ideally exceed 1.5x – 2x the daily maintenance requirements
 Replacement fluid should contain 20 meq/L of KCl and 20 meq/L of Potassium Phosphate
 Insulin and Dextrose
 Insulin infusion should be initiated at 0.1 units/kg/hr
 Add Dextrose continuing fluids once the BG level is < 300 mg/dL
 Optimum rate of decrease of BG is by < 100 mg/dL/hr
 Use “two bag system” – NS with K and D10NS with K
 Monitor with BMP every 2 hrs
 Switch to complete D10 base fluid when BG < 200 mg/dL
 Long acting insulin dose (Lantus) on the first night
 Conversion to intermittent dosing for insulin when AG is < 15
 Continue D5 NS with 20 meq/L of KCl for dehydration correction
 Monitor with Urine Ketones for clearance of ketosis
 Correct for BG and Carb intake
 Lab monitoring
 Initial Critical care panel for pH, BMP for Electrolytes and Anion Gap
 Follow up labs: BMP to monitor for AG and HCO3
 Urinalysis for urine ketones

 Intital CBC, serum Lipids, CMP might be warranted

 New onset DKA patients should get other endocrine labs for work up
Thank You