Guidelines for the Early Guidelines for the Early Management of Diabetic Management of Diabetic Ketoacidosis in ChildrenKetoacidosis in Children

Michael Bressack, MDMichael Bressack, MD

DEFINITIONDEFINITION

Hyperglycemia (serum glucose Hyperglycemia (serum glucose >300 mg/dl) with glycosuria>300 mg/dl) with glycosuria

Metabolic acidosis Metabolic acidosis (serum bicarbonate <15, (serum bicarbonate <15, elevated anion gap, pH <7.30)elevated anion gap, pH <7.30)

Ketonemia with ketonuriaKetonemia with ketonuria

CLINICAL PRESENTATION - CLINICAL PRESENTATION - HYPERGLYCEMIAHYPERGLYCEMIA

PolyuriaPolyuria PolydipsiaPolydipsia Weight lossWeight loss Dehydration/shockDehydration/shock Decreased level of consciousnessDecreased level of consciousness

CLINICAL PRESENTATION - CLINICAL PRESENTATION - METABOLIC ACIDOSISMETABOLIC ACIDOSIS

Kussmaul breathingKussmaul breathing Fruity breath (acetone)Fruity breath (acetone) ? decreased level of ? decreased level of

consciousnessconsciousness ? depressed cardiac function? depressed cardiac function ? intestinal ileus (vomiting, pain)? intestinal ileus (vomiting, pain)

LABORATORY DATALABORATORY DATA

Hyperglycemia Hyperglycemia Metabolic acidosis (anion Metabolic acidosis (anion

gap)gap) [Na[Na++]-([Cl]-([Cl--]+[HCO]+[HCO33

--])])

OH butyrateOH butyrate Low [Na+]Low [Na+]

[Na[Nacc++] = [Na] = [Namm

++] + ] + 1.6(blood glucose-100)1.6(blood glucose-100)100100

LABORATORY DATALABORATORY DATA

Hyperglycemia Hyperglycemia Metabolic acidosis (anion gap)Metabolic acidosis (anion gap)

[Na[Na++]-([Cl]-([Cl--]+[HCO]+[HCO33--])])

OH butyrateOH butyrate Low [Na+]Low [Na+] Abnormal [K+]Abnormal [K+] Pre-renal azotemiaPre-renal azotemia

MONITORINGMONITORING

Blood glucose q 1 h Blood glucose q 1 h q 4 hq 4 h Electrolytes q 1 h Electrolytes q 1 h q 4 hq 4 h Anion gap q 1 h Anion gap q 1 h q 4 hq 4 h Renal function q 4 h – q 6 hRenal function q 4 h – q 6 h Cardiac monitor/EKGCardiac monitor/EKG

CLINICAL MONITORINGCLINICAL MONITORING

CardiovascularCardiovascular Intake/urinary outputIntake/urinary output Neurologic status (Glasgow Neurologic status (Glasgow

Coma Scale)Coma Scale)

CARDIOVASCULAR CARDIOVASCULAR TREATMENTTREATMENT

Treat shock immediatelyTreat shock immediately 10-20 ml/kg doses of NS or LR10-20 ml/kg doses of NS or LR

SlowSlow rehydration for 5-15% deficit rehydration for 5-15% deficit over 48 hoursover 48 hours

SLOW REHYDRATIONSLOW REHYDRATION

Maintenance, deficit, excessive urine (because Maintenance, deficit, excessive urine (because of the risks of cerebral edema, infuse fluid at a of the risks of cerebral edema, infuse fluid at a maximal rate of 1.5 to 2 times maintenance)maximal rate of 1.5 to 2 times maintenance)

Normal saline is usually the best initial fluid Normal saline is usually the best initial fluid (avoid hypotonic fluid)(avoid hypotonic fluid)

Follow [NaFollow [Na++] closely ] closely (keep [Na(keep [Na++

correctedcorrected] ] 135meq/l)135meq/l)

TREATMENT FOR HYPER- TREATMENT FOR HYPER- GLYCEMIA / KETOACIDOSISGLYCEMIA / KETOACIDOSIS

Rehydration lowers blood Rehydration lowers blood glucoseglucose

Low-dose continuous insulin Low-dose continuous insulin (.05 - 0.1 u/kg/hr)(.05 - 0.1 u/kg/hr) IV bolus of insulin is not IV bolus of insulin is not

necessarynecessary

CONTINUOUS INSULIN DRIPCONTINUOUS INSULIN DRIP

Decrease blood glucose 50-100 mg/dl/hr Decrease blood glucose 50-100 mg/dl/hr (after the initial drop due to rehydration) (after the initial drop due to rehydration)

Add glucose to intravenous fluid when Add glucose to intravenous fluid when blood glucose <250-300 mg/dlblood glucose <250-300 mg/dl add glucose to maintenance fluids onlyadd glucose to maintenance fluids only

Increases bicarbonate and decreases anion Increases bicarbonate and decreases anion gap (takes longer to correct ketoacidosis gap (takes longer to correct ketoacidosis than hyperglycemia)than hyperglycemia) use enough insulin to correct the anion gap use enough insulin to correct the anion gap

acidosis, and add enough glucose to the acidosis, and add enough glucose to the intravenous fluid to tolerate the insulinintravenous fluid to tolerate the insulin

TREATMENT FOR K+TREATMENT FOR K+

Usually hyperkalemia on presentationUsually hyperkalemia on presentation Total body K+ deficitTotal body K+ deficit Monitor EKGMonitor EKG Initiate K+ replacement when serum level <5.5meq/l and Initiate K+ replacement when serum level <5.5meq/l and

adequate urine outputadequate urine output In the rare situation of hypokalemia at presentation, In the rare situation of hypokalemia at presentation,

immediately treat with K+ replacement and fluid therapy, but immediately treat with K+ replacement and fluid therapy, but delay insulin treatment until K+ >3.3meq/ldelay insulin treatment until K+ >3.3meq/l

INDICATION FOR INDICATION FOR BICARBONATEBICARBONATE

Life-threatening hyperkalemiaLife-threatening hyperkalemia Bicarbonate has no place in Bicarbonate has no place in

the management of DKAthe management of DKA

Cerebral edema is a Cerebral edema is a medical emergency medical emergency (major cause of death (major cause of death in pediatric DKA)in pediatric DKA)

Causes of Causes of Morbidity/Mortality in DKAMorbidity/Mortality in DKA

Cerebral edema/dysfunction (80-Cerebral edema/dysfunction (80-90% of deaths)90% of deaths)

Shock/ischemiaShock/ischemia Hyper/hypokalemiaHyper/hypokalemia HypoglycemiaHypoglycemia SepsisSepsis ARDSARDS ThrombosisThrombosis

Central venous catheters are particularly Central venous catheters are particularly prone to thrombosis. If used, prophylaxis prone to thrombosis. If used, prophylaxis with low-dose heparin should be with low-dose heparin should be considered.considered.

Cerebral Edema/CNS Cerebral Edema/CNS DysfunctionDysfunction

Clinical cerebral edema occurs in 0.5-0.9% of all episodes of DKA and Clinical cerebral edema occurs in 0.5-0.9% of all episodes of DKA and accounts for 57-87% of all DKA deathsaccounts for 57-87% of all DKA deaths

A clinical, not a radiological, diagnosis (e.g. CNS dysfunction does not A clinical, not a radiological, diagnosis (e.g. CNS dysfunction does not correlate with CT changes)correlate with CT changes)

Mortality ~25% (respiratory arrest on presentation has the worst prognosis)Mortality ~25% (respiratory arrest on presentation has the worst prognosis) Significant morbidity in survivors (~25%)Significant morbidity in survivors (~25%) Morbidity/mortality from herniationMorbidity/mortality from herniation Major cause of death in DKAMajor cause of death in DKA Occurs nearly exclusively in patients <20 years oldOccurs nearly exclusively in patients <20 years old More common in:More common in:

younger children younger children children who have a longer duration of DKA before treatmentchildren who have a longer duration of DKA before treatment children with newly diagnosed diabeteschildren with newly diagnosed diabetes elevated initial BUN elevated initial BUN low initial pCOlow initial pCO22

rapid administration of hypotonic fluidsrapid administration of hypotonic fluids failure of corrected serum sodium to rise during treatmentfailure of corrected serum sodium to rise during treatment treatment with bicarbonate treatment with bicarbonate

Occurs within first 24 hours after starting Rx (usually 4-12hrs)Occurs within first 24 hours after starting Rx (usually 4-12hrs)

Signs and Symptoms of Cerebral Signs and Symptoms of Cerebral Edema Edema

Headache, emesisHeadache, emesis Lethargy, incoherence, agitation, incontinence, comaLethargy, incoherence, agitation, incontinence, coma SeizuresSeizures Sudden, persistent bradycardia (decline >20bpm) not attributable Sudden, persistent bradycardia (decline >20bpm) not attributable

to improved intravascular volume or sleep stateto improved intravascular volume or sleep state Abnormal neurogenic respiratory pattern (e.g. tachypnea, Cheyne-Abnormal neurogenic respiratory pattern (e.g. tachypnea, Cheyne-

Stokes respiration, apneusis)Stokes respiration, apneusis) Decreasing Glasgow Coma ScaleDecreasing Glasgow Coma Scale Cranial nerve palsy (e.g. III, IV, VI) Cranial nerve palsy (e.g. III, IV, VI) Cushing’s reflex (e.g. hypertension)Cushing’s reflex (e.g. hypertension) Decorticate / decerebrate posturingDecorticate / decerebrate posturing Cardiopulmonary arrestCardiopulmonary arrest

Etiology of Cerebral Etiology of Cerebral EdemaEdema

Cerebral edema due to Cerebral edema due to osmotic shift of fluidosmotic shift of fluid

Primary ischemia/hypoxia Primary ischemia/hypoxia with secondary cerebral with secondary cerebral edemaedema

Prevention and Treatment Prevention and Treatment of Cerebral Edemaof Cerebral Edema

Cardioplumonary stabilization on presentationCardioplumonary stabilization on presentation fluid boluses of isotonic crystalloids for shockfluid boluses of isotonic crystalloids for shock intubation/ventilation for respiratory failureintubation/ventilation for respiratory failure

After acute therapy for shock, avoid excessive fluid or After acute therapy for shock, avoid excessive fluid or hypotonic fluid (use only 0.45%saline or normal saline) hypotonic fluid (use only 0.45%saline or normal saline)

Avoid medications that can mask intracranial hypertension Avoid medications that can mask intracranial hypertension e.g. phenergan, benzodiazepinese.g. phenergan, benzodiazepines

PromptlyPromptly give intravenous mannitol (0.5-1.0gm/kg) or 3% give intravenous mannitol (0.5-1.0gm/kg) or 3% saline (5-10ml/kg) for clinical signs of elevated ICPsaline (5-10ml/kg) for clinical signs of elevated ICP

Consider intubation for neurologic deterioration- risks include Consider intubation for neurologic deterioration- risks include pCOpCO22, which can elevate ICP, and , which can elevate ICP, and pCOpCO22, which causes , which causes cerebral ischemia cerebral ischemia