**• Calculate the Fluid Requirements**

**1.** Deficit Fluid Requirements :

**6.1. Laboratory tests**

300 Type 1 Diabetes

more severe cases.

**6.2. Fluids and electrolytes**

blood

**6.3. Fluids**

**•** Restoration of circulating volume

**•** Reduction of risk of cerebral edema

**•** Serum electrolytes, glucose, blood urea nitrogen, hematocrit and blood gases should be repeated 2-hourly for the first 12 hours, or more frequently, as clinically indicated, in

**•** If the laboratory cannot provide timely results, a portable biochemical analyzer that meas‐ ures plasma glucose, serum electrolytes and blood ketones on fingerstick blood samples

**◦ Anion gap = serum sodium(Na) – {serum chloride (Cl) + serum bicarbonate (HCO3)} : normal is 12 ± 2 (mmol/L).** In DKA, the anion gap is typically 20–30 mmol/L; an anion

**◦ Corrected sodium = measured Na + 2([plasma glucose -5.6]/5.6) (mmol/L)** The meas‐ ured serum sodium concentration is an unreliable index of the degree of ECF contrac‐ tion as glucose, largely restricted to the extracellular space, causes osmotic movement

**◦** Therefore, it is important to calculate the corrected sodium (using the above formula) and monitor its changes throughout the course of therapy. As the plasma glucose con‐ centration decreases after administering fluid and insulin, the measured serum sodium concentration should increase (positive sodium load), but it is important to appreciate that this does not indicate a worsening of the hypertonic state. A failure of measured serum sodium levels to rise or a further decline in serum sodium levels with therapy is

**◦ Effective osmolality (mOsm/kg)= 2x(Na + K) + glucose (mmol/L)** The effective osmo‐

**•** Improved glomerular filtration with enhanced clearance of glucose and ketones from the

**•** Establish two I.V. lines: one for fluids and electrolytes and the other for insulin infusion

of water into the extracellular space thereby causing dilutional hyponatremia.

thought to be a potentially ominous sign of impending cerebral edema

lality (formula above) is frequently in the range of 300–350 mOsm/Kg.

**•** Replacement of sodium and the ECF and intracellular fluid deficit of water

*The objectives of fluid and electrolyte replacement therapy are [1]:*

**•** Urine ketones until cleared or blood ß-OHB concentrations, if available, every 2 hours

at the bedside is a useful adjunct to laboratory-based determinations [2].

**• Additional calculations that may be informative**:

gap >35 mmol/L suggests concomitant lactic acidosis.

Patients with DKA have a deficit in extracellular fluid (ECF) volume that usually is in the range 5–10%. Clinical estimates of the volume deficit are subjective and inaccurate, therefore, in moderate DKA use 5–7%and in severe DKA 7–10% dehydration [4].



**Table 1.** Calculation of deficit fluid requirements in children presenting with DKA (1)

#### **2.** Maintenance Fluid Requirements:


**Table 2.** Calculation of maintenance fluid requirements (1)

### **3.** Total working fluid = deficit + maintenance (calculated for 48 hours)

#### **•** Type of fluids


*Correction of insulin deficiency*

**◦** Route of administration IV

used at the start of therapy

(200 mg/dL) until resolution of DKA

**6.5. Potassium replacement**

lin; e.g., infection, errors in insulin preparation.

Pathophysiology of potassium depletion in DKA [4]

major loss of potassium is from the intracellular pool.

Intracellular potassium is depleted because of the following factors:

**•** increased plasma osmolality drags water and potassium out of cells

to resolve.

cipitous.

insulin in 50 mL normal saline, 1 unit = 1 mL)

**◦** Dose: 0.1 unit/kg/hour (for example, one method is to dilute 50 units regular [soluble]

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**◦** An IV bolus is unnecessary, may increase the risk of cerebral edema, and should not be

**•** The dose of insulin should usually remain at 0.1unit/kg/hour at least until resolution of DKA (pH >7.30, bicarbonate >15 mmol/L and/or closure of the anion gap), which invaria‐

**•** If the patient demonstrates marked sensitivity to insulin (e.g., some young children with DKA, patients with HHS, and some older children with established diabetes), the dose may be decreased to 0.05 unit/kg/hour, or less, provided that metabolic acidosis continues

**•** To prevent an unduly rapid decrease in plasma glucose concentration and hypoglycemia, 5% glucose should be added to the IV fluid (e.g., 5% glucose in 0.45% saline) when the plasma glucose falls to approximately 250–300 mg/dL, or sooner if the rate of fall is pre‐

**◦** It may be necessary to use 10% or even 12.5% dextrose to prevent hypoglycemia while continuing to infuse insulin to correct the metabolic acidosis. The fall of blood glucose should not exceed 100 mg per hour. If blood glucose drops more than 100 mg/hr, re‐ duce insulin infusion to 0.05 U/kg/hr. Aim to keep blood glucose at about 11 mmol/L

**•** If biochemical parameters of DKA (pH, anion gap) do not improve, reassess the patient, review insulin therapy, and consider other possible causes of impaired response to insu‐

**•** In circumstances where continuous IV administration is not possible, hourly or 2-hourly subcutaneous (SC) or intramuscular (IM) administration of a short- or rapid-acting insulin analog (insulin lispro or insulin aspart) is safe and may be as effective as IV regular insu‐ lin infusion, but should not be used in subjects whose peripheral circulation is impaired.

Children with DKA suffer total body potassium deficits of the order of 3 to 6 mmol/kg. The

bly takes longer than normalization of blood glucose concentrations.


### *Principles of Water and Salt Replacement and Reduction of Risk of Cerebral Edema*

There is no convincing evidence of an association between the rate of fluid or sodium ad‐ ministration used in the treatment of DKA and the development of cerebral edema [26]. No treatment strategy can be definitively recommended as being superior to based on evidence. The principles described below were endorsed by a panel of expert physicians representing the Lawson Wilkins Pediatric Endocrine Society (LWPES), the European Society for Paediat‐ ric Endocrinology (ESPE), and the International Society for Pediatric and Adolescent Diabe‐ tes (ISPAD) [4,5].


#### **6.4. Insulin therapy**

Regardless of the type of diabetes, the child who presents with severe fasting hyperglyce‐ mia, metabolic derangements, and ketonemia will require insulin therapy to reverse the metabolic abnormalities [2]

DKA is caused by a decrease in effective circulating insulin associated with increases in counter-regulatory hormones {glucagon, catecholamines, growth hormone (GH), cortisol}. Although rehydration alone causes some decrease in blood glucose concentration, insulin therapy is essential to normalize blood glucose and suppress lipolysis and ketogenesis [1].

Extensive evidence indicates that '*low dose'* IV insulin administration should be the standard of care [4].

**•** Start insulin infusion 1–2 hours after starting fluid replacement therapy; i.e. after the pa‐ tient has received initial volume expansion [28].

#### *Correction of insulin deficiency*



There is no convincing evidence of an association between the rate of fluid or sodium ad‐ ministration used in the treatment of DKA and the development of cerebral edema [26]. No treatment strategy can be definitively recommended as being superior to based on evidence. The principles described below were endorsed by a panel of expert physicians representing the Lawson Wilkins Pediatric Endocrine Society (LWPES), the European Society for Paediat‐ ric Endocrinology (ESPE), and the International Society for Pediatric and Adolescent Diabe‐

**•** IV or oral fluids that may have been given in another facility before assessment should be

**•** In addition to clinical assessment of dehydration, calculation of effective osmolality may

**•** Urinary losses should not routinely be added to the calculation of replacement fluid, but

**•** The use of large amounts of 0.9% saline has been associated with the development of hy‐

Regardless of the type of diabetes, the child who presents with severe fasting hyperglyce‐ mia, metabolic derangements, and ketonemia will require insulin therapy to reverse the

DKA is caused by a decrease in effective circulating insulin associated with increases in counter-regulatory hormones {glucagon, catecholamines, growth hormone (GH), cortisol}. Although rehydration alone causes some decrease in blood glucose concentration, insulin therapy is essential to normalize blood glucose and suppress lipolysis and ketogenesis [1].

Extensive evidence indicates that '*low dose'* IV insulin administration should be the standard

**•** Start insulin infusion 1–2 hours after starting fluid replacement therapy; i.e. after the pa‐

acidosis is not corrected, add glucose 10% to isotonic saline in 1:1 ratio.

*Principles of Water and Salt Replacement and Reduction of Risk of Cerebral Edema*

from initiation of fluid therapy.

**•** Water and salt deficits must be replaced

factored into calculation of deficit and repair

may be necessary in rare circumstances.

perchloremic metabolic acidosis [27].

be valuable to guide fluid and electrolyte therapy.

tient has received initial volume expansion [28].

tes (ISPAD) [4,5].

302 Type 1 Diabetes

**6.4. Insulin therapy**

of care [4].

metabolic abnormalities [2]

	- **◦** It may be necessary to use 10% or even 12.5% dextrose to prevent hypoglycemia while continuing to infuse insulin to correct the metabolic acidosis. The fall of blood glucose should not exceed 100 mg per hour. If blood glucose drops more than 100 mg/hr, re‐ duce insulin infusion to 0.05 U/kg/hr. Aim to keep blood glucose at about 11 mmol/L (200 mg/dL) until resolution of DKA

#### **6.5. Potassium replacement**

Pathophysiology of potassium depletion in DKA [4]

Children with DKA suffer total body potassium deficits of the order of 3 to 6 mmol/kg. The major loss of potassium is from the intracellular pool.

Intracellular potassium is depleted because of the following factors:

**•** increased plasma osmolality drags water and potassium out of cells

**•** glycogenolysis and proteolysis secondary to insulin deficiency cause potassium efflux from cells

**6.7. Acidosis**

ned.

Severe metabolic acidosis is hazardous leading to decreased myocardial performance, de‐ creased response of respiratory center, peripheral and cerebral vasodilatation and life threat‐ ening hyperkalemia. Nevertheless, it can be reversible by fluid and insulin replacement; insulin stops further ketoacid production and allows ketoacids to be metabolized, which generates bicarbonate. Treatment of hypovolemia improves tissue perfusion and renal func‐

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Controlled trials have shown no clinical benefit from bicarbonate administration. Moreover, bicarbonate therapy may be more hazardous than acidosis itself. It can cause paradoxical CNS acidosis and promotes intracellular acidosis and cerebral edema. Moreover, rapid cor‐ rection of acidosis with bicarbonate causes hypokalemia, while sodium overload can result in increasing osmolality. Late alkalemia can lead to shift of oxygen dissociation curve to the

Nevertheless, there may be selected patients who may benefit from cautious alkali thera‐ py[1]. These include: patients with severe acidemia (arterial pH <6.9) in whom decreased cardiac contractility and peripheral vasodilatation can further impair tissue perfusion, and

**•** Bicarbonate administration is not recommended unless the acidosis is profound and like‐

**•** Oral fluids should be introduced only when the clinical condition has become stable,

**•** When oral fluid is tolerated, IV fluid should be reduced and change to SC insulin is plan‐

**•** To prevent rebound hyperglycemia the first SC injection should be given 15–30 minutes (with rapid acting insulin) or 1–2 hours (with regular insulin) before stopping the insulin infusion to allow sufficient time for the insulin to be absorbed. With intermediate- or long-acting insulin, the overlap should be longer and the IV insulin gradually lowered. For example, for patients on a basal-bolus insulin regimen, the first dose of basal insulin may be administered in the evening and the insulin infusion is stopped the next morning.

**•** After transitioning to SC insulin, frequent blood glucose monitoring is required to avoid

ly to affect adversely the action of adrenaline/epinephrine during resuscitation.

**6.8. Introduction of oral fluids and transition to SC insulin injections**

however mild acidosis/ketosis may still be present.

marked hyperglycemia and hypoglycemia [2].

**•** If bicarbonate is considered necessary, cautiously give 1–2 mmol/kg over 60 minutes.

left, with impaired O2 delivery to the tissues & increased anaerobic glycolysis[4].

tion, thereby increasing the excretion of organic acids[1].

patients with life-threatening hyperkalemia



Guidelines of Potassium supplementation [1]


#### **6.6. Phosphate**

Phosphate is lost as a result of osmotic diuresis in DKA. Plasma phosphate levels fall after starting treatment by insulin, which promotes entry of phosphate into cells.

Prospective studies have not shown clinical benefit from phosphate replacement. Severe hy‐ pophosphatemia in conjunction with unexplained weakness should be treated. Administra‐ tion of phosphate may induce hypocalcemia. Potassium phosphate salts may be safely used as an alternative to or combined with potassium chloride or acetate, provided that careful monitoring of serum calcium is performed to avoid hypocalcemia [2]

### **6.7. Acidosis**

**•** glycogenolysis and proteolysis secondary to insulin deficiency cause potassium efflux

**•** Potassium is lost from the body from vomiting and as a consequence of osmotic diuresis. **•** Volume depletion causes secondary hyperaldosteronism, which promotes urinary potas‐


**•** Replacement therapy is required regardless of the serum potassium concentration

itial volume expansion and concurrent with starting insulin therapy.

**•** If the patient is hypokalemic, start potassium replacement at the time of initial volume ex‐ pansion and before starting insulin therapy. Otherwise, start replacing potassium after in‐

**•** If the patient is hyperkalemic, postpone potassium replacement until the patient voids

**•** If immediate serum potassium measurements are unavailable, an ECG may help to deter‐ mine whether the child has hyper- or hypokalemia. Flattening of the T wave, widening of the QT interval, and the appearance of U waves indicate hypokalemia. Tall, peaked, sym‐

**•** The starting potassium concentration in the infusate should be 40 mmol/L or 20 mmol po‐ tassium/L in the patient receiving fluid at a rate >10 mL/kg/h. Subsequent potassium re‐

**•** Potassium replacement should continue throughout IV fluid therapy. The maximum rec‐ ommended rate of intravenous potassium replacement is usually 0.5 mmol/kg/hr

**•** If hypokalemia persists despite a maximum rate of potassium replacement, reduce the

Phosphate is lost as a result of osmotic diuresis in DKA. Plasma phosphate levels fall after

Prospective studies have not shown clinical benefit from phosphate replacement. Severe hy‐ pophosphatemia in conjunction with unexplained weakness should be treated. Administra‐ tion of phosphate may induce hypocalcemia. Potassium phosphate salts may be safely used as an alternative to or combined with potassium chloride or acetate, provided that careful

metrical, T waves and shortening of the QT interval are signs of hyperkalemia.

placement therapy should be based on serum potassium measurements.

starting treatment by insulin, which promotes entry of phosphate into cells.

monitoring of serum calcium is performed to avoid hypocalcemia [2]

from cells

304 Type 1 Diabetes

urine

rate of insulin infusion

**6.6. Phosphate**

sium excretion.

Guidelines of Potassium supplementation [1]

Severe metabolic acidosis is hazardous leading to decreased myocardial performance, de‐ creased response of respiratory center, peripheral and cerebral vasodilatation and life threat‐ ening hyperkalemia. Nevertheless, it can be reversible by fluid and insulin replacement; insulin stops further ketoacid production and allows ketoacids to be metabolized, which generates bicarbonate. Treatment of hypovolemia improves tissue perfusion and renal func‐ tion, thereby increasing the excretion of organic acids[1].

Controlled trials have shown no clinical benefit from bicarbonate administration. Moreover, bicarbonate therapy may be more hazardous than acidosis itself. It can cause paradoxical CNS acidosis and promotes intracellular acidosis and cerebral edema. Moreover, rapid cor‐ rection of acidosis with bicarbonate causes hypokalemia, while sodium overload can result in increasing osmolality. Late alkalemia can lead to shift of oxygen dissociation curve to the left, with impaired O2 delivery to the tissues & increased anaerobic glycolysis[4].

Nevertheless, there may be selected patients who may benefit from cautious alkali thera‐ py[1]. These include: patients with severe acidemia (arterial pH <6.9) in whom decreased cardiac contractility and peripheral vasodilatation can further impair tissue perfusion, and patients with life-threatening hyperkalemia


#### **6.8. Introduction of oral fluids and transition to SC insulin injections**

