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Diabetes Ketoacidosis
Dr Hessa Al Kandari
Pediatric Endocrinologist
Farwania Hospital
Page 1
Pathophysiology
Counterregulatory
hormones
( glucagon, GH,
cortisol, epinephren)
Absolute /relative
Insulin
glycogenolysis
Gluconeogeneis
Lipolysis
ketogenesis
Hyperglycemia
Ketonemia
Metabolic acidosis
Page 2
Pathophysiology
• severe depletion of water and electrolytes from intra- and
extracellular fluid compartments
• At presentation, magnitude of specific deficits depending
– duration and severity of illness
– the extent to which patient able to maintain intake of fluid and electrolytes
– content of food and fluids consumed .
• Consumption of fluids with a high-carbohydrate content (juices
or sugar containing soft drinks) exacerbate the hyperglycemia .
Page 3
Biochemical criteria
Hyperglycemia (BG >11 mmol/L)
Venous pH <7.3 or HCO3 <15 mmol/L
Ketonemia and ketonuria.
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Severity categorization
• Mild: venous pH <7.3 or HCO3 <15 mmol/L
• Moderate: pH <7.2, HCO3 <10 mmol/L
• Severe: pH <7.1, HCO3 <5 mmol/L
Page 5
Clinical manifestations
Dehydration
Rapid, deep, sighing (Kussmaul respiration)
Nausea, vomiting, abdominal pain
Progressive obtundation and loss of consciousness
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Epidemiology
677 diabetic children 12 yr , diagnosed during the period of 2000 -2006
37.7% DKA at presentation.
74.1% mild / moderate DKA.
83% of children with severe DKA were in the 0-4 yr age .
4% needed ICU care.
One child (0.15%) died cerebral edema.
Abdul Rasoul et al 2010 , Pediatric Diabetes,2010 Aug;11(5):351-6
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Epidemiology
DKA at diagnosis common
– <5 years of age
– families do not have ready access to medical care.
DKA in established T1DM
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poor metabolic control / previous episodes of DKA
peri-pubertal / adolescent girls
psychiatric disorders/ unstable family circumstance
insulin omission or failure to follow sick day or pump failure management
guidelines accounts for almost all episodes.
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Case 1
10 y/o girl, diagnosed DM1 since age of 8 yrs on insulin glargine 10
IU and premeal actrapid 4 IU . Had regular follow up; last HbA1C
was 9%.
Presented to the ER with H/O fever and runny nose for 2 days and
abdominal pain and vomiting for 1 day.
Mom admitted omitting one dose of insulin (glargine) child has poor
appetite.
Examination : conscious with acetone smell breath, congested throat
and dry mucous membranes.
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Management plan
• clinical evaluation to confirm diagnosis and determine its cause
• look for evidence of infection.
• Weigh the patient. This weight used for calculations and not the weight from a previous
office visit or hospital record.
• Assess clinical severity of dehydration.
( Clinical assessment of dehydration is imprecise, inaccurate and generally shows only fair to
moderate agreement among examiners).
• Assess level of consciousness (Glasgow coma scale)
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Management plan
• urinalysis for ketones.
• Measurement of ß-hydroxybutyrate (if available) confirm ketoacidosis
& to monitor response
• specimens for culture (blood, urine, throat).
• If lab K measurement delayed, do ECG (evaluation of K status)
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Management plan
blood sample for laboratory measurement
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serum or plasma glucose
Electrolytes, BUN creatinine, osmolality
venous (arterial in critically ill patient) pH, pCO2
Ca, Pho, mg(if possible)
HbA1c,
CBC
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Case 1
HR110/min, RR 35/min, BP 100/60 Temp 38.5 C. Her current wt 30 KG.
• Bedside Urine dipstick: glucose +4, ketones +3.
• Capillary Blood gas: PH 7.19, HCO3: 9, PO2: 10 kpa, PCO2: 3
Kpa.
• RBG 24 mmol/l.
• Na 130 mmol/L, K 4.5 mmol/L, urea 7 mmol/L, creatinin 70
mmol/L.
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Case 1
• What is the diagnosis?
• moderate DKA.
• What precipitated the acute
condition?
• Omitting insulin dose
• Upper respiratory tract
infection.
• failure to adherence to sick
days management guidelines
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Goals of therapy
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Correct dehydration
Correct acidosis and reverse ketosis
Restore blood glucose to near normal
Avoid complications of therapy
Identify and treat any precipitating event
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Case 1
What is your further management plan?
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Further clinical and biochemical monitoring
• Successful management of DKA requires meticulous monitoring of the
patient’s clinical and biochemical response to treatment so that timely
adjustments in treatment can be made when indicated by the patient’s
clinical or laboratory data .
• There should be documentation on a flow chart of hour-by-hour
clinical observations, IV and oral medications, fluids, and laboratory
results.
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Where should the child be managed?
The child should receive care in a unit that has:
• Experienced nursing staff
• Written guidelines for DKA management in children
• Access to laboratories that can provide frequent and timely
measurements of biochemical variables
• A specialist /consultant pediatrician with training and expertise in the
management of DKA should direct inpatient management.
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Monitoring
Hourly vital signs
Hourly neurological observations (GSC)
Hourly fluid input (including all oral fluid) and output.
Hourly Capillary blood glucose( cross-checked against lab).
Laboratory tests 2-hourly for the first 12 hours : serum electrolytes,
glucose, BUN, Ca, Pho,mg,Hct and blood gases repeated, more
frequently, as indicated.
• every2 hours Urine ketones until cleared or blood(BOHB) if available.
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Supportive measures
Secure the airway
deterioration in conscious level: NGT suction.
peripheral (IV) catheter : convenient .
oxygen :circulatory impairment or shock.
Antibiotics: febrile patients after cultures .
Bladder catheterization not necessary ( unconscious or unable to void on
demand )
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– Type fluid?
– Calculate Rate?
– Insulin rate?
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Principles of Water and Salt Replacement
The principles were developed after a comprehensive review of the
literature and were accepted and endorsed by a panel of expert
physicians representing the LWPES, ESPE, and ISPAD.
Pediatric Diabetes 2009: 10(Suppl. 12): 118–133
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Fluids and salt
• moderate DKA use 5–7% ; severe DKA7–10% dehydration
• IV /oral fluids given in another facility should be factored into
calculation of deficit.
• severe volume depletion, begin immediately with 0.9% saline,10
mL/kg/h over 1–2 hrs, may be repeated.
• In shock, isotonic saline (or Ringer’s lactate) 20 mL/kg boluses
infused as quickly as possible.
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Fluids and salt
• Subsequent fluid management should be with 0.9% saline or Ringer’s
acetate for at least 4–6 hours.
• Thereafter ,with solution that has a tonicity ≥ 0.45% saline with added
potassium chloride, potassium phosphate or potassium acetate
• Urinary losses not routinely be added.
• rehydrate evenly over 48 hours ( a rate rarely of 1.5–2X daily
maintenance).
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Correction of insulin deficiency
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insulin to normalize BG and suppress lipolysis & ketogenesis
‘low dose’ IV insulin is the standard of care .
insulin infusion 1–2 hours after fluid replacement therapy.
Dose: 0.1 unit/kg/hour
IV bolus may increase risk of cerebral edema
insulin remain at 0.1 unit/kg/hour at least until resolution of DKA (Ph
>7.30, bicarbonate >15 mmol/L and/or closure of the anion gap),
which takes longer than normalization of BG.
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Correction of insulin deficiency
• During initial volume expansion BG falls steeply .
• Thereafter, BG decreases at a rate of 2–5 mmol/L/hour.
• D5% should be added to IV when the BG falls to 14–17 mmol/L, or
sooner if BG falls (>5 mmol/L/h) after initial fluid expansion.
• Use D10% or D12.5% to prevent hypoglycemia while continuing
insulin to correctacidosis. ( keep BG≈11 mmol/ until resolution of
DKA).
• In marked insulin sensitivity, dose may be decreased to 0.05 unit/kg/hr,
or less, provided acidosis ct resolving.
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Acidosis
• Severe acidosis is reversible by
– fluid (improves renal function, increasing the excretion of organic acids).
– insulin (stops ketoacid production and allows ketoacids to be metabolized,
which generates bicarbonate)
• Controlled trials no benefit from bicarbonate administration
(paradoxical CNS acidosis, hypokalemia, increasing osmolality)
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Acidosis
• Bicarbonate administration is not recommended unless the acidosis is
profound and likely to affect adversely the action of
adrenaline/epinephrine during resuscitation.
• selected patients may benefit from cautious alkali therapy.
– severe acidemia (arterial pH <6.9) in whom decreased cardiac contractility
and peripheral vasodilatation can further impair tissue perfusion
– patients with life-threatening hyperkalemia
– If necessary, cautiously give 1–2 mmol/kg over 60 min .
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Case 2
1 yr 10 months old girl previously healthy presented to the emergency
room with H/O poly urea, polydypsia of 2 wks duration, and irritability
and abdominal pain for 1 day prior to admission.
Examination :drowsy (GCS 13), RR 40/mint, pulse rate: 142/mint; BP
80/50 mmHg, capillary refill 3-4 sec. Deep breathing, acetone smell
breath, severe dehydration and diaper rash.
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Case 2
– Glucocheck : 30 mmol/L
– Urine : Glucose ++++, Ketones ++++
– Capillary blood gas analysis: Ph 7; HCO3 3.8mmol/L; Pco2 2.1
Kpa.
– Na 142 mmol/L; K 5 mmol/L, urea 8 mmol/L.
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Case 2
What is your management plan?
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PICU
increased risk for cerebral edema
<5 years
severe acidosis
low pCO2
high BUN
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Case 2
Patient was started on normal saline bolus repeated and started
insulin infusion at a rate of 0.1 unit/kg/hour according to hospital
protocol; reassessed after 4 hours : the ph 7 and HCO3 4?
What actions will you take?
– Check hydration status
– Check preparation of IVF, calculation of rate, insulin preparation
& rate.
– Look for signs of infection
Page 34
Case 2
After 7 hours the K dropped to 3.4 mmol/l, Phos 0.6 mmol/l while child
was on NS with 40meq/l KCL.
How will this affect your management plan?
Page 35
Potassium replacement
In DKA total body potassium deficits 3 to 6 mmol/kg, but potassium levels
may be normal, increased or decreased .
– loss from body (vomiting ,osmotic diuresis, secondary hyperaldosteronism)
– Insulin, correction of acidosis will drive potassium into cells.
Replacement required regardless of the serum potassium level
Page 36
Potassium replacement
• If hypokalemia, start K replacement at time of initial volume
expansion and before insulin therapy.
• Otherwise, start K after initial volume expansion
• If patient hyperkalemic, defer K replacement therapy until urine
output is documented.
• The starting K concentration 40 mmol/L. Maximum rate 0.5
mmol/kg/hr.
• If hypokalemia persists, then insulin infusion rate can be reduced.
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Phosphate
Depletion of intracellular phosphate (osmotic diuresis) phosphate falls
after treatment and this is exacerbated by insulin.
Significant hypophosphatemia may occur if IV therapy without food intake
≥24 hrs .
Severe hypophosphatemia with unexplained weakness should be treated.
Potassium phosphate salts may be used as an alternative to or combined
with potassium chloride or acetate, provided careful monitoring of
serum calcium to avoid hypocalcemia
Page 38
Case 2
After 20 hours from admission clinical condition improved . Last
blood gas analysis: Ph 7.29, HCO3 14 mmol/L, PCo2 4. IVF is NSD
7.5 with 60 meq/L KCL/Kphospate. Blood glucose 10 mmol/l.
Nurse noticed that the child started to be irritable, screaming. She
checked her vitals again BP 110/70, HR 70/min.
What is the diagnosis? What is your further management ?
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Case 2
What are the risk factors for cerebral edema in the patient?
– Young age
– High urea nitrogen
– Severe DKA
– Low PCO2
40 Page 40
Case 2
– Cerebral edema
– Give manitol ; reduce IVF to 2/3 mainainence, raise the head of
the bed.
– Call the senior intensivest , consultant endocrinologist
– Order CT head
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Cerebral edema
The pathogenesis of both its initiation and progression is unclear and
incompletely understood.
usually develops 4–12 hrs after treatment , but can occur before
treatment has begun or, rarely as late as 24–48 hrs after treatment
Demographic factors associated with increased risk of cerebral edema
– Younger age
– New onset diabetes
– Longer duration of symptoms
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Epidemiological potential risk factors at diagnosis or during treatment
of DKA
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Greater hypocapnia
Increased BUN
More severe acidosis
Bicarbonate treatment
An attenuated rise in measured serum sodium concentrations during therapy
Greater volumes of fluid given in the first 4 hours
Administration of insulin in the first hour of fluid treatment
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Warning signs and symptoms of cerebral edema
• Headache & slowing of heart rate
• Change in neurological status (restlessness,
irritability, increased drowsiness, incontinence)
• Specific neurological signs (e.g., cranial nerve
palsies)
• Rising blood pressure
• Decreased O2 saturation
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Treatment of cerebral edema
• Initiate treatment as soon as suspected.
• Reduce rate of fluid by one-third.
• Give mannitol 0.5–1 g/kg IV over 20 min, repeat if no initial response
in 30 min to 2 hrs
• Hypertonic saline (3%), 5–10 mL/kg over 30 min, may be an
alternative to mannitol or a second line of therapy if there is no initial
respons to mannitol .
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Treatment of cerebral edema
Elevate the head of the bed
Intubation may be necessary for the patient with impending respiratory
failure, but aggressive hyperventilation (to a pCO2 <2.9 kPa) not
recommended( poor outcome)
After treatment started, CT scan to rule out other possible intracerebral
causes of neurologic deterioration (thrombosis or hemorrhage, benefit
from specific therapy).
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Morbidity and mortality
• mortality rate 0.15% to 0.30%.
– Cerebral edema accounts for 60% to 90% of all deaths
– 10% to 25% of survivors of cerebral edema have residual morbidity.
• Electrolyte disturbances and hypoglycemia
• CNS complications (DIC, dural sinu thrombosis, basilar artery
thrombosis) Peripheral venous thrombosis
Page 47
Take home messages
• DKA is caused by either relative or absolute insulin deficiency.
• Children and adolescents with DKA should be managed in centers
experienced in its treatment.
• Begin with fluid replacement before starting insulin therapy.
• Volume expansion (resuscitation) is required only if needed to restore
peripheral circulation.
Page 48
Take home messages
• Subsequent fluid administration (including oral fluids) should
rehydrate evenly over 48 hours at a rate rarely in excess of 1.5–2 times
the usual daily maintenance requirement.
• Begin with 0.1 U/kg/h. 1–2 hours AFTER starting fluid replacement
therapy.
• If BG decreases too quickly or too low before DKA has resolved,
increase the amount of glucose administered. Do NOT decrease insulin
infusion
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Take home messages
• Even with normal or high levels of serum potassium at presentation,
there is always a total body deficit of potassium. Begin with 40 mmol
potassium/L in the infusate.
• No evidence that bicarbonate is either necessary or safe in DKA.
• Have mannitol or hypertonic saline at the bedsid and the dose to be
given calculated beforehand.
• In profound CNS symptoms, mannitol should be given immediately.
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Diagnostic criteria
Abnormal motor or verbal response to pain
Decorticate or decerebrate posture
Cranial nerve palsy (especially III, IV, and VI)
Abnormal neurogenic respiratory pattern (grunting,Cheyne-Stokes
respiration)
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Major criteria
Altered mentation/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
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Minor criteria
Vomiting
Headache
Lethargy or not easily arousable
Diastolic blood pressure >90 mm Hg
Age <5 years
One diagnostic criterion, two major criteria, or one major and two
minor criteria (sensitivity of 92% false positive rate of 4%).
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