04 Diabetic Ketoacidosis in the Pediatric ICU[1]

8/8/2019 04 Diabetic Ketoacidosis in the Pediatric ICU[1]

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Diabetic Ketoacidosis

in the Pediatric ICU

James P. Orlowski, MD, FAAP, FCCP, FCCM*,Cheryl L. Cramer, RN, MSN, ARNP,

Mariano R. Fiallos, MDPediatric Intensive Care Unit, University Community Hospital, 3100 East Fletcher Avenue,

Tampa, FL 33613, USA

Diabetic ketoacidosis (DKA) in children is defined as a serum glucose

concentration greater than 300 mg/dL, the presence of ketones in the blood,

a blood pH below 7.3, and a serum bicarbonate level below 15 mEq/L [1].

The child who has DKA typically presents with a history of polyuria,

polydipsia, polyphagia, and weight loss. The classic clinical presentation isan acutely ill child with lethargy, dehydration, hyperpnea (Kussmaul respi-

rations), and a fruity smell (acetone) on the breath. The severity of DKA is

defined by the degree of acidosis: mild is a venous pH between 7.2 and 7.3;

moderate is a pH between 7.1 and 7.2; and severe is a pH less than 7.1 [2].

The younger the child, the more difficult it is to diagnose DKA, especially

with new-onset or previously undiagnosed diabetes mellitus (DM). Fifteen

percent to 70% of all newly diagnosed infants and children who have DM

present with DKA [2]. Infants and toddlers often are misdiagnosed as hav-

ing pneumonia, asthma, or bronchiolitis, and treatment may have beencommenced with steroids and/or sympathomimetic agents, which only exac-

erbate, and compound, the metabolic derangements. Because the diagnosis

of DM with DKA is not suspected in the young child, the duration of symp-

toms may be longer, leading to more severe dehydration and acidosis and

the possibility of obtundation progressing to coma. In a carefully analyzed

cohort of pediatric patients who had new-onset DM with DKA, 23.3% of

the children presented with DKA. Thirty-six percent of children under

5 years of age presented with DKA as the initial diagnosis, compared

with 16% of adolescents older than 14 years of age [3].

* Corresponding author.

E-mail address: [email protected] (J.P. Orlowski).

0031-3955/08/$ - see front matter 2008 Elsevier Inc. All rights reserved.

doi:10.1016/j.pcl.2008.02.015 pediatric.theclinics.com

Pediatr Clin N Am 55 (2008) 577587
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Whereas delay in diagnosis is the major contributor to DKA in previ-

ously undiagnosed DM in younger children, omission of insulin in estab-

lished DM is the leading cause of recurrent DKA and is most prevalentin adolescents. The omission of insulin may be intentional or inadvertent.

There usually is an important psychosocial reason for omitting insulin in

the adolescent. In adolescents, some 5% of patients account for more

than 25% of all admissions for DKA [4]. DKA is more common in fam-

ilies who do not have ready access to medical care for social or economic

reasons. Lower income and lower parental educational achievement are as-

sociated with a higher risk of DKA in the child [5]. Lack of health insur-

ance also is associated with higher rates and greater severity of DKA at

diagnosis, presumably because uninsured patients delay seeking timelymedical care. The risk of DKA is increased in children who have poor

control of their DM or have had previous episodes of DKA, in peripuber-

tal and adolescent girls, in children or adolescents who have clinical de-

pression or other psychiatric disorders, in children who have unstable

home situations or family dynamics, and in children receiving insulin

pump therapy [2]. The last is a significant risk factor for DKA: any mal-

function in the delivery of insulin by the pump leads rapidly to complete

insulin deficiency, because only short-acting insulin is used in pumps. Psy-

chologic or physical stress or intercurrent infection also can contribute tothe development of DKA in established DM, although these causes are

not as common in children and adolescents who are followed closely by

a diabetes care team.

Pathophysiology of diabetic ketoacidosis

A relative or absolute deficiency of insulin is the cause of DKA. The de-

ficiency of insulin can be the result of beta-cell failure in the pancreas, omis-

sion of insulin in the established DM patient, or antagonism of its action byphysiologic stress such as sepsis. With the obesity epidemic in civilized coun-

tries, cases of DKA are being seen increasingly in children who have type

2 DM with the metabolic syndrome, in which there is peripheral resistance

to insulin rather than a true deficiency of insulin. A clue to the presence of

type 2 DM is acanthosis nigricans [2].

Insulin is required for the active movement of glucose into cells as

a source of energy. In the absence of insulin, the body goes into a catabolic

state with breakdown of glycogen, protein, and fat in muscle, liver, and ad-

ipose tissue. Counterregulatory hormones such as glucagon, cortisol, growthhormone, and catecholamines stimulate glycogenolysis, gluconeogenesis,

proteolysis, lipolysis, and ketogenesis in an attempt to provide more fuel

to cells. Despite an excess of extracellular glucose, the cells sense a deficiency

of fuel for metabolic needs. The brain, with at least 20% of the bodys total

metabolic demands, cannot use fatty acids as fuel and presents a large and

inescapable need for either glucose or ketones as fuel. Ketones produced by

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the hepatic oxidation of fatty acids in a state of insulin lack and excess glu-

cagon stimulation provide an important energy source for the brain during

DKA [68].The most important perturbations seen in DKA are metabolic acidosis,

hyperosmolality, dehydration, and electrolyte disturbances. An important

hallmark of DKA is the metabolic acidosis caused by elevated plasma con-

centrations of the ketoacids acetoacetate and beta-hydroxybutyrate. Lack of

insulin permits lipolysis to accelerate in adipose tissue, releasing long-chain

fatty acids. In the liver, these fatty acids are shunted toward beta-oxidation

and ketone production because of increased glucagon levels. Ketones nor-

mally stimulate insulin release and thereby inhibit lipolysis, but in the

absence of this feedback loop extreme lipemia and ketonemia occur. Non-enzymatic decarboxylation of acetoacetate produces elevated acetone

concentrations in plasma. Typically in DKA the ratio of beta-hydroxybuty-

rate to acetoacetate is about 3:1, but it may range up to 15:1 in severe DKA

[9,10]. Acetone may represent 1.5 to 4 times the molar concentration of ace-

toacetate [11]. Acetone fills an important role as a buffer by continuous non-

enzymatic conversion of acetoacetate to acetone and carbon dioxide.

Acetone then is excreted in breath and urine in a ratio of 5:1, and the carbon

dioxide is excreted in breathing. This mechanism removes about one fourth

of the hydrogen ions generated by hepatic ketogenesis. Lactic acidosis sec-ondary to hypoxia and/or poor tissue perfusion, shifts acetoacetate toward

beta-hydroxybutyrate, reducing the bodys ability to eliminate ketoacids by

the acetone route. Lactic acidosis occurs in large part from anaerobic glycol-

ysis in hypoperfused tissues secondary to hypovolemia from osmotic diure-

sis. Measuring lactate and acetoacetate gives a crude indication of the

relative proportions of these metabolic acids. Hyperchloremic metabolic

acidosis also can be seen in DKA, most commonly as a result of aggressive

intravenous fluid resuscitation with solutions containing large amounts of

chloride [12]. The metabolic acidosis of DKA should not be treated withbicarbonate administration, because the hyperosmolar solution and the re-

sultant paradoxical cerebral acidosis may contribute to the development of

cerebral edema [13].

The hyperosmolar state induced by insulin deficiency is responsible for at

least as much of the physiologic derangements seen in DKA as the ketoaci-

dosis. The osmolality is estimated from the formula:

Osmolality 2Na K Glucose=18 BUN=2:8

where sodium and potassium concentrations are expressed in mEq/L and glu-

cose and serum urea nitrogen (BUN) concentrations are expressed in mg/dL.

In the typical child who has DKA, glucose is elevated about 400 mg/dL

above normal, and the BUN is elevated by about 15 mg/dL. These eleva-

tions result in an additional osmolar load of about 22 and 5 mOsm/L,

respectively.

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The primary fluid loss is secondary to the osmotic diuresis induced by hy-

perglycemia and glycosuria. The typical child who has DKA is about 10%

dehydrated. Estimation of the degree of dehydration is best made by knownbody weights. Unfortunately, this determination is not always possible, and

so estimates are made based on physical findings, which are based on extra-

cellular fluid volume. The extracellular fluid volume in DKA is maintained

by plasma hyperosmolality, however, so the deficit in total body water is

easily underestimated. Loss of water through osmotic diuresis is perhaps

the most dangerous process brought about by DKA. When fluid loss is se-

vere enough to begin to impair renal function (glomerular filtration rate),

the excretion of excess glucose is impaired, and hyperglycemia accelerates.

The combination of rapidly rising glucose and BUN levels results in extremehyperosmolality. Hyperosmolality has been shown to correlate better than

other laboratory measurements in DKA with levels of obtundation and

with electroencephalographic slowing [14]; hyperosmolality and its too rapid

correction may set the stage for the rare occurrence of cerebral edema dur-

ing recovery from DKA. Cardiorespiratory function can remain adequate to

sustain life even at the extremes of pH and osmolality seen in DKA, but

shock invariably occurs when dehydration is severe enough, and hypovole-

mic shock can be fatal if not reversed appropriately by volume replacement.

Hyponatremia usually is reported by the laboratory when sera fromDKA patients are analyzed, and quite commonly the reported low value

is an artifact. Extreme lipemia can decrease the measured sodium value sim-

ply by decreasing the aqueous phase of blood in which sodium predomi-

nantly resides. The true serum sodium can be calculated from the formula:

TrueNa measured Na0:021T 0:994

where T equals the triglyceride level in g/dL and sodium is expressed in

mEq/L [15].Another important cause of artifactually low sodium in DKA is hyper-

glycemia. As the amount of glucose in the extracellular fluid increases, water

shifts there from intracellular fluid, lowering the concentration of solutes,

including sodium. The classic correction is to add 2.8 mEq/L to the mea-

sured sodium for every 100-mg/dL elevation of blood glucose.

Disturbed potassium homeostasis is another potentially dangerous elec-

trolyte imbalance in DKA. Hyperkalemia commonly is found at presenta-

tion in DKA [16]. Metabolic acidosis and hyperosmolality both cause

potassium to redistribute from intracellular fluid to extracellular fluid, andcontinued osmotic diuresis results in progressive depletion of body potas-

sium stores. The best way to assess for intracellular potassium deficit is by

looking for U-waves and flattened T-waves on the EKG [17]. Insulin and

glucose are well-known treatments for hyperkalemia, facilitating the entry

of potassium into muscle cells. In the absence of insulin, hyperglycemia pro-

duces hyperkalemia, which is reversed when insulin is resupplied. When

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insulin is supplied, hypokalemia is likely to result and at times can be pro-

found, with the resultant risk of arrhythmias. It therefore is important to

provide potassium during the early stages of treatment for DKA.Profound hypophosphatemia caused by renal losses from osmotic diure-

sis is common in the presentation and early treatment of DKA. Depressed

levels of red blood cell 2,3-diphosphoglycerate have been described in

DKA [18,19]. The low levels of red blood cell 2,3-diphosphoglycerate will

decrease the partial pressure of oxygen at which hemoglobin is 50% satu-

rated with oxygen, an effect that initially is counterbalanced by the acidosis.

As the acidosis corrects, the effects of hypophosphatemia may become more

pronounced. Theoretically, hypophosphatemia can cause rhabdomyolysis,

hemolysis, muscle weakness, respiratory failure, and insulin resistance.Treatment of hypophosphatemia should be part of the initial and ongoing

treatment of DKA [20,21].

Overly aggressive treatment of hypophosphatemia can depress levels of

calcium and magnesium [21], and hypomagnesemia is common in the initial

presentation of DKA. Ionized calcium, however, usually is normal.

Hypomagnesemia can be extreme in DKA and can inhibit parathyroid

hormone response to hypocalcemia.

Management of diabetic ketoacidosis

Assess airway, breathing, and circulation (ABCs) and level of conscious-ness [1,2]. In patients who have a Glasgow coma scale score below 8 [22],

one may want to consider intubation to secure the airway and prevent

aspiration pneumonia. A nasogastric tube may be indicated to empty

the stomach and reduce the risk of aspiration. Assess circulatory status

in terms of heart rate, blood pressure, skin turgor, capillary refill, pe-

ripheral pulses, renal and cerebral perfusion, and pulse oximetry. Ad-

minister oxygen if patient is in shock or pulse oximetry is low. Weigh the patient and obtain intravenous access. Obtain a blood sample for laboratory determination of blood glucose,

electrolytes, bicarbonate, lactate, BUN, creatinine, osmolality, pH, par-

tial pressure of carbon dioxide (pCO2), arterial partial pressure of oxy-

gen (if pulse oximetry is low or unobtainable), hemoglobin and

hematocrit, complete blood cell count, calcium and ionized calcium,

magnesium, phosphorus, hemoglobin A1c, and blood beta-

hydroxybutyrate.

Obtain a urinalysis and urine for ketones. If there is evidence of infection, obtain appropriate specimens for cul-ture: blood, urine, throat, wound.

Obtain an EKG for baseline evaluation of intracellular potassiumstatus.

Assess clinical severity of dehydration: 5%: reduced skin turgor, dry mucous membranes, tachycardia



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10%: capillary refill time longer than 3 seconds, sunken eyes O10%: weak or impalpable peripheral pulses, hypotension, shock,

oliguria Fluid resuscitate to restore peripheral circulation with 10 to 20 mL/kg bo-

luses of normal saline or Ringers lactate until perfusion is reestablished.

Calculate fluid deficit based on severity of dehydration and maintenancefluid requirements and plan to replace fluid deficit (less fluid given for

resuscitation) over 24 to 48 hours in addition to maintenance fluid

requirements.

Initiate continuous low-dose insulin infusion of regular insulin at0.1 units/kg/h and continue insulin infusion until resolution of DKA

(pH O 7.30, bicarbonate O 18 mEq/L), which usually takes longerthan normalization of blood glucose concentration.

Commence replacement and maintenance fluids with normal saline with20 mEq/L of potassium acetate and 20 mEq/L of potassium phosphate.

Assess vital signs and neurologic status hourly (or more frequently ifindicated).

Assess accurate fluid input and output hourly. Measure blood glucose hourly. Reassess serum electrolytes, glucose, calcium, magnesium, phosphorus,

and blood gases every 2 to 4 hours (or more frequently if indicated),and BUN, creatinine, and hemoglobin every 6 to 8 hours until they

are normal. Calculate and follow the anion gap:

Anion gap Na K Cl HCO3

normal anion gap is 8 2

Follow urine ketones every void or every 4 hours until cleared.

When blood glucose decreases to less than 300 mg/dL, change intravenousfluids to D51/2 normal saline with 20 mEq/L potassium chloride or potas-sium acetate plus 20 mEq/L of potassium phosphate to keep blood sugar

between 250 and 300 mg/dL. It may be necessary to use 10% or even 12.5%

dextrose to maintain the blood sugar between 250 and 300 mg/dL

while continuing the insulin infusion to correct the metabolic acidosis.

If biochemical parameters of DKA (pH, anion gap) do not improve, re-assess the patient, review insulin therapy, and consider other possible

causes of impaired response to insulin such as infection or errors in in-

sulin preparation. After 36 to 48 hours, the insulin drip should be adjusted to bring theblood glucose down to the range of 150 to 200 mg/dL, and the patient

can be transitioned to oral fluids and subcutaneous insulin.

Oral fluids should be introduced only when substantial clinical improve-ment has occurred and the patient indicates a desire to eat. When oral

fluid is tolerated, intravenous fluid should be reduced.

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In patients who have established diabetes, the patients usual insulinregimen may be resumed. The most convenient time to change to sub-

cutaneous insulin is just before a meal. To prevent rebound hyperglyce-mia, the first subcutaneous injection should be given 15 to 60 minutes

(for rapid-acting insulin) or 1 to 2 hours (for regular insulin) before

stopping the insulin infusion. For newly diagnosed diabetics, the recom-

mended total daily dose (TDD) of insulin for prepubertal children is

0.75 to 1.0 units/kg and for pubertal patients is 1.0 to 1.2 units/kg.

There are two recommended regimens for administering the subcutane-

ous insulin [2]:

1. Thrice-daily administration

Before breakfast: two thirds of TDD (one third as rapid-actinginsulin; two thirds intermediate-acting insulin)

Before dinner: one third to one half of the remainder of the TDD

as rapid-acting insulin

Before bedtime: one half to two thirds of the remainder of the

TDD as intermediate-acting insulin

2. An alternative approach, called the basal-bolus method consists of

administering

One half of the TDD as basal insulin (using insulin glargine)

ANDOne half of the TDD as rapid-acting insulin divided equally

before each meal.

Blood sugars should be monitored frequently to prevent hypoglycemia orhyperglycemia. Supplemental rapid-acting insulin is given at about

4-hour intervals to correct blood glucose levels that exceed 200 mg/dL.

Cerebral edema

Symptomatic cerebral edema occurs in 0.5% to 1% of pediatric DKAepisodes and has a high mortality rate (21%24%) with a substantial pro-

portion of survivors (15%26%) left with permanent neurologic sequelae

[2]. It is one of the most dreaded complications of DKA. Its pathophysiol-

ogy and etiology are poorly understood, but it is believed that various

aspects of DKA treatment may cause or exacerbate the development of

cerebral edema [22].

The signs and symptoms of cerebral edema in DKA are:

HeadacheNew-onset vomiting

Cushings signs of slowing of heart rate and hypertension

Changes in respiratory pattern: hyperpnea, apnea, bradypnea

Change in neurologic status: restlessness, irritability, stupor

Development of pathologic neurologic signs: cranial nerve palsies, abnor-

mal pupillary reflexes, posturing



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Mild, asymptomatic cerebral edema probably is present in most chil-

dren who have DKA at the time of presentation and during therapy. Typ-

ically, symptomatic cerebral edema occurs 4 to 12 hours after the initiationof treatment for DKA, but cases have occurred before initiation of therapy

and as late as 24 to 28 hours after initiating therapy [23]. Cerebral imaging

studies have shown focal or diffuse cerebral edema, but as many as 40% of

initial CT scans in children who have DKA and clinical signs of cerebral

edema are normal [23]. Subsequent scans in these patients often demon-

strate edema, hemorrhage, or infarction. Recent MRI findings have sug-

gested that the cerebral edema in DKA is vasogenic, and not cytotoxic

[24]. Animal studies have suggested that activation of ion transporters in

the endothelial cells of the bloodbrain barrier from ketosis, inflammatorycytokines, or hypoperfusion may be responsible for fluid influx into

the brain [25]. Fluid influx into the brain from rapid declines in serum

osmolality and overly vigorous fluid resuscitation has been blamed for

the development of cerebral edema in DKA, but clinical studies do not

support these hypotheses. Associations between the rate of fluid

administration and risk for cerebral edema have been found in some

studies, but not in others, and none of the studies have found an associa-

tion between the rate of change in blood glucose values or change in

osmolality and the risk for cerebral edema [26,27]. Bicarbonate treatmentof metabolic acidosis has been implicated in causing cerebral edema in

some studies.

The children at greatest risk for developing symptomatic cerebral edema

are those who present with the greatest degree of dehydration, as reflected

by high BUN concentrations, and those who have the most profound acido-

sis and hypocapnia [26,27]. An association also has been described with

a lesser rise in serum sodium concentration as the blood glucose decreases

with treatment [28].

The treatment of symptomatic cerebral edema is mannitol, 0.25 to1.0 g/kg as a bolus, or 5 to 10 mL/kg of 3% hypertonic saline over 30 min-

utes [2]. Intubation may be necessary to protect the airway and ensure ade-

quate ventilation, but hyperventilation to a pCO2 less than 22 mm Hg

should be avoided, because one study found poorer neurologic outcome in

intubated patients who had DKA with cerebral edema who were excessively

hyperventilated [29]. Hyperventilation to a pCO2 of 25 to 30 mm Hg still

can be used to treat spikes in intracranial pressure.

The Fencl-Stewart approach to acidbase disturbancesin diabetic ketoacidosis

Hyperchloremic metabolic acidosis may be present on admission for

DKA but is extremely common during treatment of DKA [12,30]. A recent

study found that the incidence of hyperchloremia, as documented by a ratio

of plasma chloride to sodium greater than 0.79, increased from 6% on

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admission to 94% after 20 hours of treatment. After 20 hours of treatment

the mean base deficit had decreased from 24.7 mmol/L to 10.0 mmol/L, but

the proportion that was caused by hyperchloremia had increased from 2%to 98% [12]. These authors estimated plasma ketonemia using the albumin-

corrected anion gap:

Anion gap Na K Cl TCO2 0:25 40 albuming=L

One then can measure the unmeasured ion effect and the chloride effect

from the following equations:

Unmeasured ion effectmEq=L standard base excess

sodium=chloride effect

albumin effect

where standard base excess is measured from a blood gas machine.

Sodium=chloride effectmEq=L Na Cl 38

and

Albumin effectmEq=L 0:25 42 albuming=L

and

Chloride effectmEq=L 102 Cl 140=Na

Summary

DKA is a common, life-threatening complication of DM in children.

Central nervous system changes seen in DKA include the altered sensorium

seen commonly in DKA and loosely characterized as diabetic coma and the

uncommon but worrisome progressively deepening coma caused by cerebral

edema, which has both a high morbidity and mortality.

References

[1] Dunger DB, Sperling MA, Acerini CL, et al. European Society for Paediatric Endocrinol-ogy/Lawson Wilkins Pediatric Endocrine Society consensus statement on diabetic ketoaci-

dosis in children and adolescents. Pediatrics 2004;113:e13340.

[2] Wolfsdorf J, Glaser N, Sperling MA. Diabetic ketoacidosis in infants, children, and adoles-

cents. A consensus statement from the American Diabetes Association. Diabetes Care 2006;

29:11509.

[3] Rewers A, Klingensmith G, Davis C, et al. Diabetic ketoacidosis at onset of diabetes: the

SEARCH for diabetes in youth study [abstract]. Diabetes 2005;54(Suppl 1):A63.



10/11

[4] Edge JA, Hawkins MM, Winter DL, et al. The risk and outcome of cerebral oedema

developing during diabetic ketoacidosis. Arch Dis Child 2001;85:1622.

[5] Rewers A, Chase HP, Mackenzie T, et al. Predictors of acute complications in children with

type 1 diabetes. JAMA 2002;287:25118.

[6] Schade DS, Eaton RP. Dose response to insulin in man: differential effects on glucose and

ketone body regulation. J Clin Endocrinol Metab 1977;44:103853.

[7] Miles JM, Gerich JE. Glucose and ketone body kinetics in diabetic ketoacidosis. Clin Endo-

crinol Metab 1983;12:30319.

[8] Cryer PE. Glucose counterregulation in man. Diabetes 1981;30:2614.

[9] Sperling MA. Diabetic ketoacidosis. Pediatr Clin North Am 1984;31:591610.

[10] Halperin ML, Bear RA, Hannaford MC, et al. Selected aspects of the pathophysiology of

metabolic acidosis in diabetes mellitus. Diabetes 1981;30:7817.

[11] Owen OE, Trapp VE, Skutches CL, et al. Acetone metabolism during diabetic ketoacidosis.

Diabetes 1982;31:2428.

[12] Taylor D, Durward A, Tibby SM, et al. The influence of hyperchloraemia on acid base

interpretation in diabetic ketoacidosis. Intensive Care Med 2006;32:295301.

[13] Rose KL, Pin CL, Wang R, et al. Combined insulin and bicarbonate therapy elicits cerebral

edema in a juvenile mouse model of diabetic ketoacidosis. Pediatr Res 2007;61:3016.

[14] Tsalikian E, Becker DJ, Crumrine PK, et al. Electroencephalographic changes in diabetic

ketosis in children with newly and previously diagnosed insulin-dependent diabetes mellitus.

J Pediatr 1981;98:3559.

[15] Goldman MH, Kashani M. Spurious hyponatremia in diabetic ketoacidosis with massive

lipid elevations. J Med Soc N J 1982;79:5912.

[16] Fulop M. Serum potassium in lactic acidosis and ketoacidosis. N Engl J Med 1979;300:

108790.[17] Malone JI, Brodsky SJ. The value of electrocardiogram monitoring in diabetic ketoacidosis.

Diabetes Care 1980;3:5437.

[18] Gibby OM, Veale KE, Hayes TM, et al. Oxygen availability from the blood and the effect of

phosphate replacement on erythrocyte 2,3-diphosphoglycerate and haemoglobin-oxygen

affinity in diabetic ketoacidosis. Diabetologia 1978;15:3815.

[19] Clerbaux T, Reynaert M, Willems E, et al. Effect of phosphate on oxygen-hemoglobin

affinity, diphosphoglycerate and blood gases during recovery from diabetic ketoacidosis.

Intensive Care Med 1989;15:4958.

[20] Keller U, Berger W. Prevention of hypophosphatemia by phosphate infusion during

treatment of diabetic ketoacidosis and hyperosmolar coma. Diabetes 1980;29:8795.

[21] Becker DJ, Brown DR, Steranka BH, et al. Phosphate replacement during treatment ofdiabetic ketoacidosis: effects on calcium and phosphorus homeostasis. Am J Dis Child

1983;137:2416.

[22] Fiordalisi I, Novotny WE, Holber D, et al. An 18-yr prospective study of diabetic ketoaci-

dosis: an approach to minimizing the risk of brain herniation during treatment. Pediatr

Diabetes 2007;8:1429.

[23] Krane EJ, Rockoff MA, Wallman JK, et al. Subclinical brain swelling in children during

treatment of diabetic ketoacidosis. N Engl J Med 1985;312:114751.

[24] Roberts JS, Vavilala MS, Schenkman KA, et al. Cerebral hyperemia and impaired cerebral

autoregulation associated with diabetic ketoacidosis in critically ill children. Crit Care Med

2006;34:221723.

[25] Lam TI, Anderson SE, Glaser N, et al. Bumetanide reduces cerebral edema formation in ratswith diabetic ketoacidosis. Diabetes 2005;54:5106.

[26] Glaser NS, Wootton-Gorges SL, Marcin JP, et al. Mechanism of cerebral edema in children

with diabetic ketoacidosis. J Pediatr 2004;145:16471.

[27] Glaser N, Barnett P, McCaslin I, et al. Risk factors for cerebral edema in children with

diabetic ketoacidosis: the Pediatric Emergency Medicine Collaborative Research Committee

of the American Academy of Pediatrics. N Engl J Med 2001;344:2649.

586 ORLOWSKI et al


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