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Diabetic ketoacidosis in children

Article  in  Sri Lanka Journal of Child Health · August 2012

DOI: 10.4038/sljch.v41i3.4604

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Nalin C Kitulwatte
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Current Practice

Diabetic ketoacidosis in children

Nalin C Kitulwatte1

Sri Lanka Journal of Child Health, 2012; 41: 134-138

(Key words: Type 1 diabetes mellitus; diabetic ketoacidosis; children; cerebral oedema; serum osmolality;
hypertonic saline; mannitol; mechanical ventilation)

Introduction Pathophysiology4,5

Diabetic ketoacidosis (DKA) is a life-threatening, The primary abnormality in DKA is insulin

preventable complication of diabetes mellitus. It is deficiency. It causes hyperglycaemia by increased
characterized by inadequate insulin action, gluconeogenesis, accelerated glycogenolysis and
hyperglycaemia, dehydration, electrolyte loss, impaired peripheral glucose utilization1. When the
metabolic acidosis and ketosis1. DKA is the most serum glucose level exceeds the renal threshold of
frequent cause of paediatric intensive care unit 180 mg/dl, an osmotic diuresis occurs, resulting in
(PICU) admissions and deaths in children with type 1 the loss of extracellular water and electrolytes.
diabetes mellitus (T1DM)1. About 15-70% of all Furthermore, physiologic stress caused by
DKA occur at the presentation of T1DM2. However, dehydration and coexistent infection, stimulate the
children already diagnosed as T1DM can develop release of counter-regulatory hormones such as
DKA due to non-compliance with insulin therapy, glucagon, catecholamines and cortisol. They further
insulin pump failure or intercurrent illness2. Cerebral exacerbate hyperglycaemia by increasing hepatic
oedema is the most serious complication of DKA in glucose production and further impairing peripheral
children. It is common in young children newly glucose uptake5.
diagnosed as T1DM and is rare in individuals more
than 20 years of age3. A high index of suspicion is Counter-regulatory hormones, particularly
warranted because, although uncommon, it is the epinephrine, also promote lipolysis, free fatty acid
major cause of morbidity and mortality in DKA3. release, and subsequently, ketoacidosis through the
oxidation of free fatty acids to ketone bodies.
Diagnosis Accumulation of ketoacids is the primary cause of
the metabolic acidosis in DKA. Acetone is also
The diagnosis of DKA can be missed as it can formed and gives a fruity odour to the breath, but it
resemble other more common paediatric illnesses does not contribute to the acidosis. The increasing
such as severe dehydration and acute severe asthma1. levels of hyperglycaemia and acidosis contribute to a
DKA should be considered in any child or young vicious cycle: osmotic diuresis leads to intravascular
adult with respiratory distress, dehydration, acidosis volume depletion, which decreases renal blood flow
or mental status changes4. The presence of DKA is and glomerular perfusion, limiting the body's ability
supported by a history of polyuria, polydipsia, to excrete glucose and worsening the
vomiting, weight loss and rapid breathing with fruity- hyperglycaemia. Progressive dehydration and
smelling breath1. The diagnosis of DKA is based on acidosis further stimulate the release of counter-
biochemical evidence of hyperglycaemia (serum regulatory hormones, which accelerates the
glucose levels >200mg/dl), acidosis (venous pH <7.3 production of glucose and ketoacids. More severe
and/or serum bicarbonate levels <18mEq/l) and dehydration then leads to poor peripheral perfusion,
ketosis or ketonuria. DKA may be categorized as causing lactic acidosis. Abdominal pain and vomiting
mild (venous pH of 7.2–7.3), moderate (venous pH occur as a result of the intestinal ileus brought on by
7.1–7.2), or severe (venous pH <7.1) 1. ketoacids and dehydration, preventing patients from
_________________________________________ maintaining hydration with oral fluids. In the setting
1
Consultant Paediatric Intensivist, Paediatric of metabolic acidosis, potassium (K) is transported
Intensive Care Unit, Lady Ridgeway Hospital for out of the cell into the plasma in exchange for
Children, Colombo hydrogen and is lost in the urine. Thus, virtually all
patients with DKA develop a deficiency of total body
K, regardless of their serum K level. Phosphate,
another predominantly intracellular ion, is handled 2mOsm/hour) and prevent excessive free water
similarly. accumulation. Serial calculations of effective
osmolality (2 sodium + glucose) are recommended,
The pathogenesis of cerebral oedema in DKA is not as sodium levels that fail to rise with treatment may
well understood. It has been postulated that certain signify excessive free water accumulation and an
elements of treatment (high doses of insulin, rapid increased risk of cerebral oedema)10. Generally, fluid
administration of hypotonic fluid, administration of replacement with 0.9% normal saline is provided at
intravenous bicarbonate) may cause cerebral least during the first 6 hours1. Hyponatraemic fluids
oedema6-9. However, cerebral oedema is evident in should be avoided as there is a potential risk of life
many patients even before treatment is initiated9. threatening cerebral oedema8-10.
Recent studies suggest that the development of
cerebral oedema may be linked to a loss of cerebral Electrolyte Therapy
autoregulation and a vasogenic mechanism8,9.
Potassium1,4,5
1,4,5,10
Management Although the serum potassium (K) level at
presentation is often normal or elevated, the total
The killer in DKA and its management is cerebral body K is low and should be replaced. Early K
oedema (CE). Thus, the aim of management is replacement is also important to prevent the K
correcting metabolic abnormalities while preventing depletion during therapy. With the initiation of
CE. Because common management practices may be insulin therapy and correction of acidosis, serum K
linked to the development of cerebral oedema, the levels may drop precipitously as K shifts back from
use of these interventions must be employed the extracellular to the intracellular compartment.
judiciously. Therapy of DKA consists of fluid and Unless the patient exhibits hyperkalaemia (serum K
electrolyte replacement, insulin administration, and level >5.5mEq/L) or anuria, K should be added to the
careful ongoing monitoring of clinical and laboratory intravenous fluids at the beginning of the second hour
factors. of therapy. Otherwise K is added as soon as urine
output is established or the hyperkalaemia abates. If
The osmotic diuresis and the compromised fluid the patient presents with hypokalaemia, (serum K
intake (due to nausea and vomiting) result in a large level <3mEq/L) K replacement is initiated
water and electrolyte deficit so that intravenous fluid immediately. Most patients require 30 to 40mEq/L of
replacement should begin as soon as the diagnosis of K in the replacement fluids, with adjustment based on
DKA is established. Initial fluid therapy is aimed at serum K concentrations that are measured frequently.
rapid stabilization of the circulation to correct
impending shock. However, too rapid fluid Phosphate
administration should be avoided. Fluid replacement DKA results in significant phosphate depletion.
in excess of 4 L/m2/24 hours has been associated with Furthermore, serum phosphate values decrease
the development of potentially fatal cerebral oedema during treatment. Hypophosphataemia may cause
in DKA1. For this reason, an initial fluid bolus metabolic disturbances. However, clinical studies
(10ml/kg) is usually advised only in vascular have not shown benefit from phosphate replacement
decompensation (extreme tachycardia, hypotension, during the treatment of DKA. Phosphate replacement
cold extremities, and/or anuria) to expand the should be given if the values decrease below 1
vascular compartment and improve peripheral mg/dl4,5.
circulation. Once the patient has been stabilized,
subsequent rehydration is accomplished with caution. Bicarbonate
The fluid deficit should be corrected gradually, over Bicarbonate losses are significant in DKA. However,
36-48 hours. during the treatment of DKA, the patient can produce
bicarbonate. Insulin stimulates the generation of
Fluid Administration bicarbonate from the metabolism of ketones.
Consistent with this, clinical trials have failed to
The degree of dehydration in these patients is show any benefit of bicarbonate administration.
frequently overestimated11. Deficits should be Potential risks of bicarbonate therapy include
estimated at 5-7% of body weight unless shock is paradoxical central nervous system acidosis,
present when 10-15% loss of body weight is exacerbation of hypokalaemia and cerebral oedema.
assumed. Rehydration fluids should contain at least Therefore, bicarbonate treatment should be
115-135mEq/L of sodium chloride to ensure a considered only in cases of extreme acidosis
gradual decline in serum osmolality (1.5– (pH<6.9) which impairs cardiovascular stability after
the fluid resuscitation or as treatment of life- Clinical monitoring is essential: vital signs,
threatening hyperkalaemia. If bicarbonate perfusion, input/output balance, and neurologic status
administration is believed to be necessary, 1 to should be documented at least hourly. Cardiac
2mmol/kg (added to 0.9% saline) should be provided monitoring is recommended due to the risk of
over 1 to 2 hours1,4,5. dysrhythmia. Laboratory monitoring should include
venous blood sugar concentrations hourly and
Insulin1,4,5 electrolytes and venous pH every 2-4 hours until
normal. Lack of improvement in clinical and
Serum glucose concentration often falls significantly biochemical parameters with time suggests an occult
with initial rehydration alone due to increased infection or inadequate insulin or fluid replacement.
glomerular filtration from improved renal perfusion.
Therefore insulin treatment is begun after the initial Cerebral oedema
fluid resuscitation i.e. at the beginning of the second
hour of therapy. Insulin is administered as a DKA is the most frequent diabetes-related cause of
continuous intravenous infusion of regular insulin at death in children. Acute cerebral oedema, accounts
a rate of 0.1units/kg per hour. Early insulin infusion for 75-87% of the mortality in DKA10. Cerebral
during the initial rehydration and insulin bolus oedema is more likely to occur in patients at the time
therapy increase the risks of cerebral oedema due to of first diagnosis of diabetes, younger children, and
rapid drop of serum osmolality10. The aim of insulin those presenting with the most severe degree of
therapy is gradual reduction of the blood glucose and dehydration and metabolic derangement7. It typically
suppression of ketoacidosis. However, resolution of develops within the first 24 hours of treatment of
the acidosis in DKA invariably takes longer than the DKA6. Symptoms and signs include headache,
time to achieve a normal blood glucose confusion, slurred speech, bradycardia, hypertension
concentration. The temptation to decrease the rate of and other signs of increased intracranial pressure. A
insulin administration based on glucose values should common proposed mechanism of cerebral oedema
be resisted because this practice delays resolution of involves a rapid decline in serum osmolality10. Rapid
the acidosis. administration of fluid, hypotonic fluids, insulin
boluses and rapid drop in blood sugar all can cause a
Dextrose (5% increasing to 12.5% as necessary) rapid decline in serum osmolality during the
should be added to the intravenous solutions when treatment of DKA10.
the serum glucose level is <250–300 mg/dl with the
goal of keeping the serum glucose level in the range Management of cerebral oedema should be initiated
of 150–250 mg/dl to avoid rapid drop in serum with clinical suspicion without waiting for a
osmolality10. The insulin dose should be decreased radiological diagnosis. It is aimed at lowering
only if hypoglycaemia or a rapid reduction of serum intracranial pressure by prompt administration of IV
glucose persists despite administration of maximal mannitol or hypertonic saline and preventing rapid
dextrose concentrations in the intravenous fluid. If drop in serum osmolality by reducing rates of fluid
the acidosis is not resolving, the insulin dose should and insulin administration4,5. Tracheal intubation to
be increased to 0.15 or 0.2 units/kg per hour. Insulin mechanically hyperventilate and surgical
should be administered intravenously until the ketosis decompression with ventriculostomy are less
and acidosis improves. When ketoacidosis has successful at preventing mortality or severe
resolved (venous pH >7.3 and serum bicarbonate disability. Intracranial imaging to exclude other
level >18mEq/L), a short-acting subcutaneous insulin pathologies, such as cerebral infarction or
with a longer-acting preparation is given in thrombosis, should be obtained but not at the expense
combination with a snack or meal. Intravenous of timely therapeutic interventions1,5,9.
insulin should be continued, to allow time for the
subcutaneous insulin to act. Urine ketones Conclusion
(acetoacetate) will take longer to disappear and do
not need to be cleared before starting subcutaneous DKA is the major cause of severe morbidity and
insulin1,4,5. mortality in children with T1DM. However they can
be managed successfully with minimal complications
Monitoring1,4,5 by early recognition and proper fluid and electrolyte
management aimed at avoiding rapid drop in plasma
Successful management of DKA requires meticulous osmolality.
attention to clinical and laboratory changes. Most
children with DKA should be treated in a PICU.
 DKA MANAGEMENT ALGORITHM

HISTORY: Some or all of the following: Polyuria, polydipsia, CLINICAL SIGNS: Deep sighing respirations (Kussmaul breathing) with no
weight loss, abdominal pain, tiredness, vomiting, confusion, wheeze or rhonchi, smell of ketones on breath, lethargy/ drowsiness,
difficulty in breathing dehydration

DKA CONFIRMED
Urine ketones/glucose * Ketonuria
Capillary /venous blood - glucose, * Glucose >200mg/dl
Blood gases, electrolytes, urea, creatinine * pH <7.3
* Serum bicarbonate < 18mmol/L

Hypotension (< 5 percentile for age)

<4y < 70/30 VASCULAR DECOMPENSATION
4 -10y < 80/40 (with or without coma) NO VASCULAR DECOMPENSATION
10-13y < 85/40 * Hypotension (see box)
>13y < 90/42 * Decreased level of consciousness
Clinically dehydrated Minimally dehydrated
Hyperventilating Tolerating fluids orally
RESUSCITATION OR Normal bowel sounds
* Airway/NG tube - if otherwise needed. Vomiting
* N/Saline 10 ml/kg rapidly to expand vascular Normal BP
space Then
* Decrease to 5 ml/kg/hour Oral hydration
SC insulin
N/Saline 7ml/kg over 1st hour
Then 3-5 ml/kg/hour, including
insulin infusion below

After one hour start insulin infusion at 0.1 units/kg/hr = 1 ml/kg/hr of solution of 25 units of Regular insulin in 250cc N/saline
DO NOT GIVE BOLUS OF INSULIN
If History of voiding within last hour and (K+) < 5.5mmol/L, add 40meq /L of KCL to IV fluid. Aim to keep (K+) between 4-5meq/L

ACIDOSIS IMPROVING
NEUROLOGICAL DETERIORATION Blood glucose <270 mg/dl or blood glucose falls
ACIDOSIS NOT IMPROVING >90mg/dl/h
Headache, irritability, decreased level of consciousness, (In 3-4 hours)
Decreased heart rate Change IV to 5% dextrose with normal saline
* Check insulin delivery system Decrease insulin to 0.04-0.05 U/kg/h
* Consider sepsis Blood glucose <180mg/dl
Change IV to 10% dextrose with normal saline
First rapidly exclude hypoglycemia
by capillary blood glucose measurement
THEN
Improvement:
Treat for cerebral oedema
Clinically well
Tolerating oral fluids
pH > 7.3
* 20% Mannitol 5cc/kg over 20 minutes HCO3 > 18mmol/L
* If Na has declined administer 2-4 ml/kg of 3% saline over 10-20 min Start SC insulin
* Decrease insulin to 0.04 - 0.05 U/kg/hr Stop IV insulin 1/2 hour after SC dose
* Admit to ICU Determine cause of DKA

OBSERVATION AND MONITORING

* Hourly blood glucose (capillary)
* Aim for a decrease in blood glucose of < 90mg/dl/h
* Hourly documentation of fluids input / output
* Hourly assessment of neurological status
* 2-4 hourly - electrolytes, venous gases
* Follow Effective Osmolality = (2 x measured Na + measured blood glucose)
* Avoid a decrease of > 2 - 3mmol/L/hour in effective osmolality by increasing IV sodium concentration
 References 6. Daniel LL. Cerebral oedema in diabetic
ketoacidosis. Pediatr Crit Care Med 2008;
1. Stuart A, Weinzimer MF, Canarie EVS, et al. 9(3): 320-9.
Disorders of glucose homeostasis. In: Nichols
DG, Editor. Roger's Textbook of Pediatric
Intensive Care, 4th ed. Lippincott Williams & 7. Glaser N, Barnett P, McCaslin I, et al. Risk
Wilkins, 2008. factors for cerebral oedema in children with
diabetic ketoacidosis. New England Journal
2. Rewers A, Chase HP, Mackenzie T, et al. of Medicine 2001; 344:264–9.
Predictors of acute complications in children
with type 1 diabetes. Journal of the American 8. Glaser N: Cerebral oedema in children with
Medical Association 2002; 287:2511-8. diabetic ketoacidosis. Current Diabetes
Reports 2001; 1:41–6.
3. Couch RM, Acott PD, Wong GW. Early
onset fatal cerebral oedema in diabetic 9. Silver M, Clark C, Schroeder M, et al.
ketoacidosis Diabetes Care 1991; 14: 78-9. Pathogenesis of cerebral oedema after
treatment of diabetic ketoacidosis. Kidney
4. Cooke DW, Plotnick L. Management of International 1997; 5:1237–44.
diabetic ketoacidosis in children and
adolescents. Paediatrics in Review 2008; 10. Bohn D, Hoorn EJ, Carlotti CP, et al.
29:431-5. Preventing a drop in effective plasma
osmolality to minimize the likelihood of
5. Nicole AS, Levitsky LL, Management of cerebral oedema during treatment of children
with diabetic ketoacidosis. The Journal of
diabetic ketoacidosis in children and
Pediatrics 2007; 150; 467-73.
adolescents. Pediatric Drugs 2008; 10(4):
209-15. 11. Koves IH, Neutze J, Donath S, et al:
Improving our estimate of dehydration in
DKA. Diabetes Care 2004; 27:2485–7

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