Diabetic Ketoacidosis (DKA)

Biochemical Criteria
● CBG > 200 mg/dL (hyperglycemia)
● Venous pH < 7.3 or HCO3 <15 mmol/L
● Blood beta-hydroxybuyrate > 3 mmol/L or moderate to large ketonuria (> 2+)

Clinical Signs
● Dehydration
● Tachycardia
● Tachypnea
● Kussmaul’s breathing
● Ketone/acetone breath
● Nausea
● Vomiting
● Abdominal pain
● Blurry vision
● Confusion
● Drowsiness
● Progressive decrease in LOC >> loss of consciousness

Risk Factors
Newly Diagnosed
● Younger age
● Delayed diagnosis
● Lower socioeconomic status
● Lives in low prevalence DM 1 country

Known Diabetes
● Poor compliance to insulin
● Limited access to medical services

Pathophysiology
● Results from deficiency of circulating insulin and increased levels of catecholamines,
glucagon, cortisol, and growth hormone
○ Severe: Occurs in previously undiagnosed T1DM or poor compliance to insulin, reduced
doses of insulin, concurrent AGE
● Relative insulin deficiency
○ When counterregulatory hormones are markedly increased d/t stress (sepsis, trauma,
febrile illness)
○ Lead to metabolic decompensation

1. Absolute/Relative insulin deficiency + high counterregulatory hormone conc

 2. Accelerated catabolic state with increased glucose production by liver and kidney (via
glycogenolysis and gluconeogenesis) and impaired peripheral glucse utilization
3. Hyperglycemia and hyperosmolality

● Increased lipolysis and ketogenesis

○ Causing ketonemia and metabolic acidosis
● Hyperglycemia > 180 mg/dL + hyperketonemia lead to
○ osmotic diuresis
○ dehydration
○ obligatory loss of electrolytes
◆ Worsened by vomiting associated with severe ketosis
These changes stimulate further stress hormone production >> more severe insulin
resistance >> worsening hyperglycemia & hyperketonemia >> lactic acidosis from hypoperfusion/
sepsis

● Still with normal or high blood pressure due to:

 ○ Increased catecholamines in plasma
○ Increased ADH in response to hyperosmolality (increases BP via V2 receptors)
○ Increased osmotic pressures from marked hyperglycemia

Severity
PH HCO3 (mmol/L)
MILD < 7.30 < 15
MODERATE < 7.20 < 10
SEVERE <7.10 <5

Initial Assessment (ER)

● HGT
● Blood/ urine ketones
● Serum electrolytes
● ABG
● Severity of dehydration
● LOC
Diagnostic Management
● Serum/plasma Glucose
● Electrolytes
● BUN, creatinine
● Serum osmolality
● Venous pH, pCO2
● CBC
○ Increased WBC in response to stress
 ● Albumin, Calcium, Phosphate, Magnesium
● Urinalysis for ketones
● Blood culture (if with fever)
● ECG (for baseline evaluation of K; if lab result is delayed)
● HbA1c

Management
GOALS OF THERAPY
● Correct dehydration
● Correct acidosis & reverse ketosis
● Gradually restore hyperosmolality & CBG to near normal
● Monitor for complications of DKA
● Identify and treat precipitating event

Fluid Replacement
● Started before Insulin
● Aim: replace fluid deficit over 24 to 48 hours
● Deficit in ECF volume 5 - 10% of body weight
○ Moderate DKA: 5 - 7% dehydration
○ Severe DKA: 7 - 10% dehydration
 ● Degree of ECF Contraction markers:
○ Increased BUN
○ Increased Hct/Hb
○ Increased albumin or total protein
○ Serum Na unreliable
◆ Glucose is restricted to ECF >> osmotic movement of water into ECF >>
dilutional hyponatremia
◆ Low Na content of the elevated lipid fraction of serum
● Objectives:
○ Restore circulating volume
○ Replace Na and ECF, ICF water deficits
○ Improve glomerular filtration
○ Enhance clearance of glucose & ketones from blood

Volume Depleted but not in shock DKA in shock

0.9% saline to restore peripheral Isotonic saline 20 ml/kg infused
circulation asap via large bore cannula
10 ml/kg over 30 - 60 minutes Reassess circulatory status after
each bolus
Poor tissue perfusion: initial bolus
can be given over 15-30 minutes +
second bolus to ensure adequate
perfusion
● Deficit Replacement
○ IVF: 0.45% to 0.9% Saline or Balanced salt sol (Ringer’s lactate, Hartmann’s, or
Plasmalyte)
● Aim: gradually reduce serum osmolality to normal
○ Na should increase as Glucose decreases (0.5 mmol/L for each 1 mmol/L decrease in
glucose)
◆ If fails to rise, Na conc of fluid should be increased
● Hyperchloremia
○ Cl:Na > 79%
○ Chloride = acid; mask recognition of resolution of ketoacidosis
○ If this develops, persisting base deficit or low HCO3 conc can be seen as d/t ketosis
○ Monitor via bedside BOHB levels
○ Chloride-induced base deficit = (Na - Cl - 32)
○ use Potassium Acetate instead of KCl, for IVF: ringer’s lactate/ Plasmalyte

Insulin Therapy
● Purpose:
 ○ restore normal cellular metabolism
○ Suppress lipolysis and ketogenesis
◆ Normalize blood glucose conc
● 0.05 to 0.1 U/kg/hr at least 1 hour AFTER starting fluid replacement
○ Must not be given at start of therapy
◆ Increases risk of cerebral edema
◆ Precipitate shock via rapidly decreasing osmotic pressure
◆ Exacerbate hypokalemia
● Mechanism:
○ aldosterone-like effect leading to increased urinary K excretion
● Glucose conc decreases 2 - 5 mmol/L/hr
○ Prevention of rapid decline in glucose: add 5% glucose to IVF
◆ Glucose decrease by 250 - 300 mg/dL
● Use 10-12.5% dextrose to prevent hypoglycemia while giving insulin to correct met acidosis

Potassium
● Defer until UO is documented if hyperkalemic
● 40 mmol/L or 20 mmol/L if fluid rate at > 10 ml/kg/hr
○ Rate: 0.5 mmol/kg/hr
● DKA Deficit: 3 - 6 mmol/kg
● Loss of intracellular K
○ Transcellular shift d/t hypertonicity (increased plasma osmolality causing solvent drag;
water and K drawn out of cells
○ Acidosis
○ Glycogenolysis and proteolysis secondary to insulin deficiency
○ Vomiting & osmotic diuresis (lost from body)
○ Volume depletion >> secondary hyperaldosteronism promoting urinary excretion of K
● Start replacement if hypokalemic. If not, replace after fluid resus
● ECG (hypokalemia)
○ Prolonged PR interval
○ T wave flattening and inversion
○ ST depression
○ U waves
○ Long QT interval

Bicarbonate
● Only recommended for life-threatening hyperkalemia or severe acidosis (vpH <6.9) with
evidence of compromised cardiac contractility
● 1 to 2 mmol/kg over 60 minutes

Monitoring of Clinical and Biochemical Status

● V/S with neurovitals Q1
○ Neuro: to check for warning signs of cerebral edema
○ Rapidly increasing Na conc
 ◆ May indicate diabetes insipidus; loss of urinary free water
◇ Interruption of blood flow to pituitary gland d/t cerebral herniation
● Amount of insulin given
○ Adequate: decrease in serum BOHB by 0.5 mmol/L/hr
◆ Increase dose if not at this rate of improvement
● I&O Q1
● HGT Q1
● Labs: serum elec, glucose, BUN, Ca, Mg, PO4, Hct, ABG, blood BOHB (if available) every 2-4
hrs
● Resolution of DKA
○ PH > 7.3
○ HCO3 > 15 mmol/L
○ BHOB < 1 mmol/L
○ Closure of anion gap

Formula Normal DKA

Anion gap Na - (Cl + 12 + 2 mmol/L 20 - 30 mmol/L;
HCO3) >35 mmol/L =
concomitant
lactic acidosis
Corrected Measured Na + 2
sodium ([Glucose - 5.6]/
5.6) OR
Measured Na + 2
([Glucose - 100]/
100) mg/dL
Serum 2 x (Na) + 275 - 295 300 - 350
Osmolality Glucose (in mOsm/kg mOsm/kg
mmol/L)
Complications of Therapy
● Cerebral Edema
● Hypokalemia
● Hyperchloremic Acidosis
● Hypoglycemia
● Inadequate Rehydration
Cerebral Edema
Warning S/Sx
● Headache after starting treatment
● Progressive worsening/ severe headache
● Bradycardia not related to sleep or improved intravascular volume
● Change in neurological status
○ Restlessness
○ Irritability
○ Increased drowsiness
○ Confusion
○ Incontinence
● Specific neurological signs
● Rising BP
● Decreased SpO2

Risk Factors
● Elevated serum urea nitrogen
● Severe acidosis
● Severe hypocapnia
● < 5 years old

Diagnosis
● Develops within first 12 hrs after treatment started or as late as 24 - 48 hrs after
● Criteria (1 Diagnostic/ 2 major/ 1 major + 2 minor) = 92% sensitivity
○ Diagnostic
◆ Abnormal motor or verbal response to pain
◆ Decorticate or decerebrate posture
◆ Cranial nerve palsy (especially III, IV, and VI)
◆ Abnormal neurogenic respiratory pattern (eg, grunting, tachypnea, Cheyne-
Stokes respiration, apneusis)
○ Major
◆ Altered mentation, confusion, fluctuating level of consciousness
◆ Sustained heart rate deceleration (decrease more than 20 beats per minute) not
attributable to improved intravascular volume or sleep state
◆ Age-inappropriate incontinence
○ Minor
◆ Vomiting
◆ Headache
◆ Lethargy or not easily arousable
◆ Diastolic blood pressure >90 mm Hg
◆ Age <5 years
● Diabetes Insipidus
○ Increased urine output + marked increase in serum Na
○ Loss of free water in urine
 ○ sign of cerebral herniation
◆ Causes interruption of blood flow to pituitary gland

Treatment
● Adjust fluids given to maintain normal BP while avoiding too much fluid given
○ Avoid hypotension bec it might compromise CPP
● Mannitol 0.5 to 1 g/kg IV over 10 - 15 minutes
○ Lasts about 120 minutes
○ Dose can be repeated after 30 minutes
● Hypertonic saline (3%) 2.5 to 5 mlkg over 10 - 15 minutes (alternative or add-on)
○ Given if no response to mannitol within 15 - 30 mins
○ 2.5 ml/kg is equimolar to mannitol 0.5 g/kg
● Head elevation to 30 deg, position at midline
● Intubation if with impending respiratory failure
● Cranial imaging after treatment
○ To check for intracranial hemorrhage or thrombosis
○ Done if considering encephalopathy or acute focal neurologic deficit
○ Suggestive findings: focal or severe progressive headache, focal neurologic deficit

Hyperglycemic Hyperosmolar State (HHS)

– Extremely elevated serum Glucose
– Hyperosmolality without significant ketosis
– Less frequent in pediatric patients
–
Criteria
● Glucose >33.3 mmol/L (600 mg/dL)
● Venous pH > 7.25; arterial pH > 7.30
● HCO3 > 15 mmol/L
● Small ketonuria, absent to mild ketonemia
● Serum osmolality > 320 mOsm/kg
● Altered consciousness or seizures (approx 50%)

Management
GOALS OF THERAPY
● Expand the intra- and extravascular volume
● Restore normal renal perfusion
● Promote a gradual decline in corrected serum Na and serm osmolality

Management
● Fluid therapy
● Insulin at 0.025 to 0.05 U/kg/hr once CBG decreases < 3 mmol/L (50 mg/dL) per hour with
fluid alone