Page 1

Diabetes Ketoacidosis

Dr Hessa Al KandariPediatric Endocrinologist

Farwania Hospital

Page 2

Pathophysiology

Absolute /relative Insulin

Counterregulatory hormones

( glucagon, GH, cortisol, epinephren)

catabolic state

Hyperglycemia Ketonemia

Metabolic acidosis

glycogenolysisGluconeogeneis

Lipolysisketogenesis

Page 3

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 4

Biochemical criteria

Hyperglycemia (BG >11 mmol/L)

Venous pH <7.3 or HCO3 <15 mmol/L

Ketonemia and ketonuria.

Page 5

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 6

Clinical manifestations

Dehydration

Rapid, deep, sighing (Kussmaul respiration)

Nausea, vomiting, abdominal pain

Progressive obtundation and loss of consciousness

Page 7

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

Page 8

Epidemiology

DKA at diagnosis common– <5 years of age– families do not have ready access to

medical care.DKA in established T1DM

– 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.

Page 9

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.

Page 10

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)

Page 11

• 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)

Management plan

Page 12

blood sample for laboratory measurement– serum or plasma glucose– Electrolytes, BUN creatinine, osmolality– venous (arterial in critically ill patient)

pH, pCO2– Ca, Pho, mg(if possible)– HbA1c, – CBC

Management plan

Page 13

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.

Page 14

• What is the diagnosis?

• What precipitated the acute condition?

• moderate DKA.

• Omitting insulin dose

• Upper respiratory tract infection.

• failure to adherence to sick days management guidelines

Case 1

Page 15

Goals of therapy

• Correct dehydration• Correct acidosis and reverse ketosis• Restore blood glucose to near normal• Avoid complications of therapy• Identify and treat any precipitating

event

Page 16

What is your further management plan?

Case 1

Page 17

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.

Page 18

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.

Page 19

• 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.

Monitoring

Page 20

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 )

Page 21

–Type fluid?

– Calculate Rate? – Insulin rate?

Page 22

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

Page 23

• 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.

Fluids and salt

Page 24

• 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).

Fluids and salt

Page 25

Correction of insulin deficiency

• 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.

Page 26

• 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.

Correction of insulin deficiency

Page 27

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)

Page 28

• 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 .

Acidosis

Page 29

Page 30

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.

Page 31

–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.

Case 2

Page 32

Case 2

What is your management plan?

Page 33

PICU

increased risk for cerebral edema <5 years severe acidosislow pCO2

high BUN

Page 34

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

Case 2

Page 35

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?

Case 2

Page 36

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 37

• 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.

Potassium replacement

Page 38

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 39

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 ?

Page 40

What are the risk factors for cerebral edema in the patient?–Young age–High urea nitrogen–Severe DKA–Low PCO2

40

Case 2

Page 41

–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

Case 2

Page 42

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

Page 43

Epidemiological potential risk factors at diagnosis or during treatment

of DKA– 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

Page 44

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 nervepalsies)• Rising blood pressure• Decreased O2 saturation

Page 45

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 .

Page 46

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).

Treatment of cerebral edema

Page 47

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 48

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 49

• 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

Take home messages

Page 50

• 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.

Take home messages

Page 51

Page 52

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)

Page 53

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

Page 54

Minor criteria

VomitingHeadache Lethargy or not easily arousableDiastolic blood pressure >90 mm HgAge <5 yearsOne diagnostic criterion, two

major criteria, or one major and two minor criteria (sensitivity of 92% false positive rate of 4%).