Diabetic ketoacidosis (DKA) still remains an The majority of DKA episodes are thought to be due
important cause of diabetes-related deaths in children to insulin omission or treatment error. The other
despite frequent updates of internationally agreed causes include inadequate insulin therapy during
guidelines. The majority of guidelines are consensus intercurrent illness, alcohol, and technical errors, e.g.
rather than evidence based. However, knowledge of a malfunctioning pen, leaking cartridge or insulin
the pathophysiology and evidence based management pump failure5,6.
strategies help to understand the rationale behind the
consensus guidelines of DKA1. Pathophysiology
The length of history is very important in DKA is characterized by severe depletion of water
determining the severity of DKA, particularly with and electrolytes from both the intra- and extracellular
respect to the symptom of deep breathing, fluid compartments; the range of losses is shown in
drowsiness, and vomiting. Symptoms that suggest a Table 1.
Table 110
Losses of fluids and electrolytes in DKA and maintenance requirements in normal children
Fluid/Electrolyte Average (range) losses per kg 24-hour maintenance requirements
Water 70 ml (30100) *10 kg 100 ml/kg/24 hr
1120 kg 1000 ml + 50 ml/kg/24 hr for each kg
from 1120
>20 kg 1500 m + 20 ml/kg/24 hr for each kg >20
Sodium 6 mmol (513) 24 mmol
Potassium 5 mmol (36) 23 mmol
Chloride 4 mmol (39) 23 mmol
Phosphate (0.52.5) mmol 12 mmol
*the Holiday-Segar formula
Despite their dehydration, patients continue to elevated just above 400 mg/dl, and the BUN is
maintain normal blood pressure and have elevated by about 15mg/dl9.
considerable urine output until extreme volume
depletion and shock supervene. This eventually At presentation the magnitude of specific deficits in
causes severe impairment of renal excretory function an individual patient varies depending on the duration
such as excretion of glucose, ketones and hydrogen and severity of illness, the extent to which the patient
irons. This leads to rapid rise of glucose and blood was able to maintain intake of fluids and electrolytes
urea nitrogen (BUN) levels resulting in extreme and content of food and fluids consumed before
hyperosmolality. seeking medical attention14.
Osmolality = 2 (Na + K) + (glucose)/18 + (BUN)/ 2.8 Early Kussmaul breathing can be easily missed as it
mOsm/kg is the depth rather than the rate of breathing that is
striking. The level of consciousness needs to be
Sodium and potassium concentrations are expressed assessed by using the Glasgow Coma Score (Table 2)
in mEq/L and glucose and BUN are expressed in and fundi need to be examined.
mg/dl. In a typical child who has DKA, glucose is
Table 2
Glasgow Coma Scale
The patients have to be screened for possible sepsis It is also important to recognize that overlap between
as a precipitating cause, both clinically and with the the characteristic features of hyperglycaemic
help of laboratory investigations. Fever is an hyperosmolar state (HHS) and DKA may occur.
unreliable indicator of infection as it is commonly Some patients with HHS, when there is severe
absent in DKA. Its presence, however, is indicative dehydration, have mild to moderate acidosis,
of infection. Overall, it is wise to have a low conversely some children with type I DM may have
threshold to treat very sick patients with antibiotics1. features of HHS if high carbohydrate containing
It is also very important to weigh patients if possible, beverages have been used prior to diagnosis16.
even if they are very sick. This allows accurate
calculations for fluid and insulin administration. The criteria for HHS16 are:
The severity of DKA is categorized by the degree of Plasma glucose concentration >33.3 mmol/L
acidosis15. (600mg/ dl )
Arterial pH >7.3
Mild : venous pH< 7.3 or bicarbonate Serum bicarbonate >15 mmol /L
<15mmol/L Small ketonuria, absent to mild ketonaemia.
Moderate: pH <7.2,bicarbonate <10 mmol/ L Serum osmolality >320 mOsm/kg
Severe : pH <7.1, bicarbonate <5 mmol/L Stupor or coma.
Management of DKA (Figure 1)17
Continuous cardiac monitoring to assess T waves for 100 ml/kg for first 10kg
evidence of hyper or hypokalaemia is also very 50 ml/kg for second 10kg
important20,21. 20ml/kg for subsequent kilograms
Deficit (litres) = % of dehydration x body weight in therapy. There is no need for an initial bolus. Make
kg up a solution of 1 unit per ml, of human soluble by
adding 50 unit (0.5ml) insulin to 50ml of 0.9% saline
Add calculated maintenance (for 48 hours) and in a syringe pump. Do not add insulin directly to the
estimated deficit, subtract the amount already given fluid bag. The solution should then run at
as resuscitation fluid, and give the total volume 0.1unit/kg/hour. There are some who believe that
evenly over 48 hours1, 17, 26 . 0.05unit/kg/hour is an adequate dose. There is no
firm evidence to support this .The aim of treatment is
Hourly rate = 48 h maintenance + deficit resuscitation fluid to achieve a gradual fall in blood glucose, which does
48 not exceed 5mmol/l/h. If blood glucose falls too
rapidly insulin dose can be reduced to 0.05U/kg/h17.
Type of fluid
Once blood glucose reaches 12mmol/l, the
Initially use 0.9% saline with 20 mmol KCL in intravenous fluids should be changed to 0.45% saline
500ml, and continue this for at least 12 hours until and 5% dextrose. It is very important that insulin is
blood glucose falls to 12mmol/l, then if plasma not stopped and the dose is not reduced below
sodium level is stable change to 500ml bags of 0.45% 0.05U/kg/h because only insulin can switch off
saline /5%glucose/20mmol KCL. If the plasma ketone production. Some suggest also adding glucose
corrected sodium level falls during treatment, then if the initial rate of fall of blood glucose is greater
continue with normal saline with or without added than 5-8 mmol/l per hour, to protect against cerebral
dextrose depending on blood sugar level17. oedema. There is no good evidence for this practice,
and blood glucose levels will often fall quickly
Corrected sodium = measured Na + (2 x (blood purely because of rehydration17. If blood glucose falls
glucose- 5.5) /5.5) below 4mmol, give a bolus of 2 ml/kg of 10%
dextrose and increase the glucose concentration of
Serum sodium usually rises as the blood glucose falls the infusion. If needed, solution of 10% glucose wit
and this may be associated with increased risk of 0.45% saline can be made up by adding 50ml of 50%
cerebral oedema. Theoretically serum sodium should glucose to a 500ml bag of 0.45% saline /5% glucose
rise by 2mmol for every 5.5 mmol fall in blood with 20mmol KCL.
glucose10.
If biochemical parameters of DKA (pH, anion gap)
During initial fluid resuscitation if plasma glucose
do not improve, reassess the patient, review insulin
concentration falls steeply >5mmol/L/h, consider
therapy, and consider other possible causes of
adding glucose even before plasma glucose has
impaired response to insulin; e.g.
decreased to 12mmol/L27. In addition to clinical
assessment of dehydration calculation of osmolality
Insufficient insulin to switch off ketones.
may be valuable to guide fluid and electrolyte
therapy. Inadequate resuscitation.
Sepsis
Insulin therapy Hyperchloraemic acidosis due to excess 0.9%
saline
Once dehydration fluids and potassium are running, Salicylate or other drugs.
blood glucose levels will start to fall. Therefore do
not start insulin until intravenous fluids have been In circumstances where continuous IV administration
running for at least an hour. There is now evidence is not possible, hourly or two hourly SC or IM
that too early insulin treatment has been found to be a administration of short or rapid acting insulin analog
risk factor for the development of cerebral oedema28. (insulin lispro or insulin aspart) is safe and may be as
However, insulin therapy is essential thereafter to effective as IV regular insulin infusion30-35 but should
correct hyperglycaemia, inhibit lypolysis, ketogenesis, not be used in subject whose peripheral circulation is
and glycogenolysis and to counteract the excessive impaired. Initial dose SC: 0.3unit/kg, followed one
levels of stress hormones29. hour later by SC insulin lispro or aspart at 0.1
unit/kg/h or 0.15-0.2 units/kg every two hours.
Continuous low dose intravenous infusion is the
preferred method. Because insulin is adsorbed to the
plastic IV tubing, a volume (about 50ml) of infusion
should be run through the tubing before initiating
Potassium replacement Thrice daily administration
Before breakfast: two third of TDD (1/3 as rapidly
Total body potassium is always substantially depleted acting insulin; 2/3 as intermediate acting insulin)
in DKA, and the major loss is from the intracellular Before lunch: One third to one half of the remainder
pool as a result of hypertonicity, insulin deficiency of the TDD as rapid acting insulin.
and exchange for hydrogen ions with in the cell. Before dinner: One half to two thirds of the
Intravenous fluids and insulin administration will remainder of the TDD as intermediate-acting insulin.
drive potassium back into the cells resulting in a
rapid fall in serum potassium. Therefore potassium Blood sugar should be monitored two hourly to
replacement should be started as soon as resuscitation prevent hypoglycaemia or hyperglycaemia.
is completed provided anuria is not reported by the Supplemental rapid acting insulin is given at four
family and the ECG does not show elevated T waves. hourly intervals to correct blood glucose levels that
Ensure that every 500ml bag of fluid contains exceed 200mg/dl9.
20mmol KCL and check BUN and electrolytes 2
hourly after initial resuscitation1. Or
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