1. health and fitness
2. disease
3. diabetes

Guidelinesfor the Managementof
DiabeticKetoacidosis
Definitionof DiabeticKetoacidosis
D
K
A
II.
Hyperglycernia
Ketonemia/ketonuria
Acidosis
Blood sugar> 200 mg/dl
p H < 7 . 3o r I I C O j < l 5 n r E q / l -
Pathophysiolosy
Insulindeficiencyhasthreemain effects:
L Lossof insulin-dependent
glucosetransportinto peripheraltissues
2. Increasedgluconeogenesis
in the liver
3. Increasedbreakdownof fat, protein,andglycogen
Thus, insulin deficiency results in hyperglycemia(from increasedhepatic glucose
prodttctionand decreased
peripheraluptake)and acidosis(primarily derivedfrom hepatic
fatty acidoxidationinto ketoacids).
Ilyperglycetniaabovethe renal threshold(>180-200mg/dl) resultsin glycosuria. This
producesan osmoticdiuresisthat dragssolutes(Na, K, Cl, PO4)along with it, leadingto
dehydrationand electrolytelosses. With significantdehydration,there may be poor
perfusionof peripheraltissuesleadingto lactic acidosis,which further aggravatesthe
existingketoacidosi
s.
I II.
Assessmcnt
A. History
Tlte classic symptornsof new-onsetdiabetesmellitus are polyuria, polydipsia, and
polyphagiaaccompaniedby weight loss. Theremay be a history of weakness,malaise,
or lethargy. Often the acute crisis will be precipitatedby an acute infection or stress.
Nausea,vomiting, abdominal pain, alteredbreathing,or progressiveobtundationmay
precipitatethe visit to the EmergencyDepartment. In children known to have diabetes,
DKA is usuallypreventable.It is often precipitatedby poor compliancewith the home
managcmcntroutitrcor failureto increaseinsulindoseswith an intercurrentillness.
B. PhysicalExarn
l.
Airway -- may be compromisedin patientswith extremeobtundation.Consideration
shouldbe given to intubationand mechanicalventilationif the patientis not making
adecluate
respiratorycompensation
for the metabolicacidosis.
DKA Guidelines
25-April-06
2. Breathing-- typically deep,hyperpneic(Kussmaul). Breathsoundsshouldbe clear;
ralcs/rhonchirnay suggestintercurrentinfectionor pulmonarycdema(lvhich can be
seenin the correctionof DKA).
3. Circulation-- particularattentionshouldbe paid to pulse,blood pressure,capillary
refill, and any orthostaticchanges. Childrenwith DKA are hyperosmolar,so that
intravascularflLridsare sparedat the expenseof cellular fluids. Therefore,the
clinicalexatninatiotr
underestimates
the degreeof dehyclration.
4. Mental status-- A lull neurologicalexaminationmust be performedon all patients
presentingin DKA, so that a baselinemay be establishedto which subsequent
examinationsmay be compared. Acute deteriorationsin menlal statusmay herald
cerebraledema(seesectionon cercbraledema).
5. Abdonren -- many patients in DKA complain of abdominal pain, often due to
persistentvomiting or ketosis. Tendernesstends to improve with treatment;pain
which remainsor worsensshould prompt considcrationof other diseaseprocesses
(e.g.,appendicitis).
C. Initial laboratorytcsts
The laboratory confirmation of thc cliagnosisof diabetes mellitus requires only a
fingerstickblood sugar and urinalysisto confirm the hyperglycemia,glycosuriaand
ketonuria,but in DKA additionallaboratorytestsare useful in assessingthe severityof
illnessand guidingtreatment.
1. Electrolytes The sodium is typically low, as a result of urinary losses,
hyperglycenria,and hypertriglyceridemia(artefactualhyponatremia). For every 100
mgldL glucoseabove200 mg/dl,, the measureNa shouldbe reducedby I .6 mEqil.
N&.u..".t.,I :
+ 1.6
N&,r'r.nrur.,r
x
[Glucose]- 200
t00
Potassiummay be low, normal, or elevated,but the total body storesare always depleted.
Bicarbonatevalues are usually low, consistentwith metabolic acidosis. BUN and
Creatinineareusuallyelevatedwith dehydration.Glucoseis invariablyelevatedin DKA.
2.
Venousblood gas -- will documentmetabolicacidosis. Arterial blood gas should
alsobe consideredin the appropriatcsettingof severeclinical decompensation.
3.
Calciunr.Phosphorus-- Phosphatelevels are usually low due to urinary losses.
Iteplacementof phosphatein the rehyclrationfluids nray precipitatetetanyin patients
with low calcium levels. If the initial calcium and phosphoruslevels are closeto
normal,thereis no needto keeprepcatingthem.
DKA Guidelines
25-April-06
IV.
4.
CBC w/ differential -- ElevatedWBC countsand "left shifts" are often seenwith the
acutc stressof DKA and do not necessarilyindicate an aoute infectiousprocess.
Furthermore,significantinfectionmay be presentevenin the absenceof fever.
5.
Additionallaboratorytestswill dependon the clinical situation.
Goalsof Therapv
In planningtreatment,it is irnportantto considerthe importantcomplicationsof DKA:
A. Cardiovascularcollapse
1. Fromdchydration
2. Treatnrentinvolvesintravascularfluid expansionwith ISO'|ONIC fluids (saline)
B. Overwhclmingacidosis
l. From ketoacidproductionand lacticacid accumulation
2. Volurneexpansionand tissuereperfusionto oorrectlactic acidosis
3. Pronrptinitiationof insulinto stopfatty acid oxidationand ketoneproduction
4. Consideruse of sodium bicarbonatein patientswith arterial pH < 6.9 and/or
evidenceof myocardialdepression
C. Ilypokalcmia
with rapidintracellularmovementof potassium
l. lnsulin therapyis associated
2. Adequatepotassiumreplacement
in rehyclration
fluids and frequentmonitoring
rvithbloodtestsand EKG's
D. CerebralEdem:r
L llypertonic dehydralionin DKA is associated
with the productionof osmotically
-(taurine,
particles
in
the
inositol
active
brain
formerly "idiogenicosmoles")that
act to preventneuronalcellulardehydration.
2. Correctionof hyperosmolarstateleadsto fluid influx into the brain. Rapid rates
of rehydrationor correction of hyperosmolaritymay lead to cerebral cellular
swellingand brain herniation.It usuallyoccurs6-18 hoursinto therapy,just as the
patient appearsto be clinically and biochernicallyimproving. This is the most
contntoncauseo-f'mortaliqtin children with DKA !!!
3. Muclr of the etiology and pathophysiology
of cerebraledemais still unknown,but
the risk shouldbe niinimizedbv attentionto the followins:
(over48 hrs) with isotonicfluids
a. Slorvfluid replacement
b, Irrequentmonitoringand slow rise of calculatedCORRECTEDNa values
c. Close neurologicsurveillancefor early signsof increasedICP (headache,
lethargy,slurredspeech,obtundation)and rapid evaluation& action
DKA Guidelines
25-April{6
V.
'Ireatment
A. Initial Resuscitation
Obviously, adequate airway patency and brcathing should be assessedfirst, and
immediateinterventionsmade as needed. Initial fluid resuscitationshould always be
witlr normal saline, 10-20 cclkg. Remember.rapid fluid replacementis potentially
dangerous,so thotrghtfirl considerationof fluid needs should guide treatment,not
"automatic"reaotions.After each l0-20 cclkg aliquot,pulse,blood pressure,orthostatic
The aim is
changes,intake/output,perfusion,and blood glucoseshouldall be reassessed.
lrot to completelynormalizethe vital sigrisbut to ittrprovethem.
B. Insulin
The initial doseis usually 0.1 Units/kg/hour.For profoundhyperglycemia(BG > 1000)
lower rates(0.05-0.75Units/kg/hr)may be preferable.The goal is to
or hyperosmolarity,
lower the serumglucoseby 50-100mg/dl/hr.
When the blood sugar falls below 250 mg/clt., dcxtrose should be added to the
rehydrationfluids. A "two-bag" infusion system, in which one bag containsDro
is convenientfor titrating the slorv,
(+electrolytes)and the other D6 (+-electrolytes),
glucose.
scrttm
steadydcclinein
Two - bag sysfetn for DKA
(t)
DoNS
KCI + KP04
(2)
DroNS
KCI + KP04
'Ihe
llrst bag (l) contains nornral saline and some concentration ofKCl and K-Phosphate. The second bag (2) contains the
s a m e c o n c e n t r a t i o no f e l c c t r o l y t e s ,b u t a l s o h a s D l 0 . T h e t r v o s y s t c m s a r e n l n o n s e p a r a t cp u m p s u r d Y ' d i n t o t h e p a t i e n t .
D e x t r o s e c o n c e n t r a t i o n sn r a - vt -l r u s b c t i t r a t c d r a p i d l y t n d e a s i l y a s n e e d e d : e . g . , r u n n i n g b a g ( l ) l t 10 0 c c l h r a n d ( 2 ) a t 0
c c / h r - n o d c x t r o s e ,r v h i l e r u n n i n g b o t h a t 5 0 c c l h r g i v e s a f i n a l c o n c e n t r a t i o no l ' D 5 .
DKA Guidelines
25-April-06
C. Acidosis
The most importantstepsin treatingacidosisare the prompt institution of insulin and
adequatefluid resuscitationfor tissue reperfusion. Sodium bicarbonateshould be
if:
considered
1. Arrerialpl l < 6.9
'fhere
2.
is evidenceof cardiovasculardysfunction,such as poor contractilityor
peripheralvasodilation
The dosemay bc calcul:rteby the formula
Dose(mliq): weight(kg) x 0.3 x (15 - [HCOr1)
Alternatively,a reasonable
doseis l-2 mEq/kg. Bicarbonateshouldalwaysbe given as a
SLOW infusion over l-2 hours, not as a bolus. Rapid pH changesmay precipitate
hypokalemiaor cause a paradoxicalCNS acidosis(which may worsen the patient's
mental status). Failure of the acidosisto improve in responseto bicarbonatesuggests
inadequate
volume status.respiratorycompromise,or severesystemicinfection(sepsis).
Recentevidencehas called into questionthe utility of bicarbonateadministration.and
most studiesshorv that bicarbonateuse does not hastenresolutionof DKA or shorten
hospitalizations.
D. Rehydration fluids
Dehydrationin DKA is predominantlyintracellular. Clinical estimatesof percent
'l'herefore,
dehydrationare often highly inaccurate.
CLOSE MONITORING OF
INTAKE/OUTPUT AND FREQUENT REASSESSMENT OF FLUID NEEDS is
critical. Calculationsshould aim to restorethe fluid deficit slowllr and evenly over 48
hours. The fluid replacementrate must be titrated to the clinical setting; i.e., the
calculatedNa rate should RISE with treatment. A FALL IN T'HE CALCULATED
SODIUM SHOULD PROMPT AN IMMEDIATE DECREASE IN THE FLUID RATE.
Resuscitationfluids should be subtractedfrom the fluid deficit. Replacementof fluids for
urinary lossesis not needed,bccauseurinary lossesare usually negligibleafter the first
several hours of treatmcnt. THE RESUSCIT'ATIONFLUID SHOULD ALWAYS BE
NORMAL SALINE. Thereafter,normal saline and'/, normal saline can be used,although
we prefer nonnal saline. Hypotonic fluid replacementincreasesthe risk of cerebral
edema. In prolbund hypernalremia, 213 or 3/4 NS may be considered after the
hyperglycemiahasbeencorrected.
DKA Guidelines
25-April-06
E. Electroll'tcrcplacenrent
1.
2.
Sodium- Total body Na deficit of 8-10 mEq/kg as a result of osmoticdiuresis.
Calculationof dellcits and rcplacementsare generallynot needed. The initial
rehydrationfluids in DKA should almost always be normal saline to protect
againstcerebraleclema,changedto 3/aor t/znornlal salineas neededlater.
'l'otal
body K cleficitof 8-l0 mEq/kg as a result of osmoticdiuresis.
Potassium-f-lor.vever.
serllmK+ may be normalor evenelevated,becauseacidemiacausesa
II+/K+ exchangethat rnoves K+ out of the cells into the intravascularspace.
ScrurnK+ falls r.viththerapy,becauseof correctionof acidemiaand the direct
action of insulin on cellular K+ uptake. Potassiumshould be added to the
replacenrent
lluids as soonas the abscnceof renalfailureis shown:
K+ < 3.0mEq/L
K + : 3 . 0 - 6 . 0m E q / t ,
K+ > 6.0mEq/I.
60 mEq/L
40 mllq/L
holdK
Occasionally,replacementratesas high as 80 mEq/L may be needed.Rates> 80
mEq/L shouldbe given via centralvenousaccess. Potassiumreplacementrates
greaterthan 0.5 mEq/kg/hrshouldbe avoided. Serumpotassiumlevelsshouldbe
known beforeinsulin is given. FormalIIKG shouldbe consideredin patientswith
serumpotassiumlevels< 3.0 or -' 6.0 mEq/L.
3.
Phosphate-- To correct phosphatedepletion, and to prevent hyperchloremia
(rvhich often occurs during treatmentof DKA), the potassium is generally
replacedas:
PotassiumChloride* PotassiumPhosphate,
in a l:1 ratio
This methodoffers the advantageof replacingphosphate,which improvesoxygen
and energydelivery,throughthe formationof ATP and2,3-DPG.
Calcium shouldbe monitoredwhen receivingsupplementalphosphate.
** If potassiumphosphateis not available,standardKCI may still be given +*
VI.
Monitorins
Treatmentof DKA requiresfrequenteyes-on.hands-on,brain-onreassessment.
DKA
should never be "auto-pilot" or managedfrorn the call room. Frequentbedside
review of clinical data, includingvital sign changes,perfusion,mental status,I/O's,
and labs.is essential.
DKA Guidelines
25-April-06
A. Neurologicalreassessment
shouldbe performedq lhr
B. Blood glucoseshouldbe measuredqlhr while on an insulin infusion
C. Electrolltesq2hr until calculatedNa and K arenormal and measuredHCO3> 15,
then q4hr until infusionsare d/c'd. More frequentmonitoringmay be necessary
if
the calculatedNa falls at any time.
D. BuN/Creatinine, calcium and phosphorusno more frequently than q4-6hrsunless
clinically indiczrted.
E. Serial measurementsof arterial pl{ may be necessaryin intubatedpatients,those
with extreme life-threateningacidosis,or after bicarbonatetherapy. These
patientsshould have intra-arterialcathetersplaced and be monitored in the ICU.
SerialVBG's may be discontinuecl
onceHCOr > 15.
F. All patientsshouldbe on telemetry.
G. Central venous cathetersshould be consideredin patients with evidenceof
impairedrenal function,pulmonaryedema,or in other situationsof complicated
fluid management.
H. Intracranialpressuremonitors ("bolts") should be consideredin any patient with
cerebral edema and neurologic deterioration. Immediate brain imaging and
neurosurgical
consultationarerequiredin this setting.
VII.
The Hieh-Risk Patient
Patientswith the following characteristics
may requireICU admission:
A.
B.
C.
D.
E.
F.
G.
H.
DKA Guidelines
Age<3years
Significantlyalteredor deterioratingmentalstatus
pH<7.2
Glucose> 1000mg/dl
Na (calculated)> 160or any patientwith falling (calculated)Na
K < 3.5 mEq/L on admission
> 350 mOsm)
Severehyperosmolality(Sor,n
Otherorgansystemdysfunctionthat complicates
treatment
25-April-06
VIII.
Transitionto Subcutaneous
Insulin
A. When dehydration,acidosis and hyperglycemiaare corrected(glucose< 300
mg/dl,pl-l > 7.3, tlClOr > 15).and patientis clinically hydratedit is time to begin
feeding the patient and plan for subcutaneous
insulin. The patient should be
changcdto subcutaneous
insulin afler toleratingoral nutrition well, and at a time
of a major meal(breakfastor dinner).
B. Subcutaneous
insulin may also be starleddirectly in new onsetDM. if the patient
is not in kctoacidosis.
fbr initialdosesas lbllows:
C. Guidelines
l. Total dosefor day : 1.0unit/kglday
2. AM:213 of total dosewith ll3 as Humalogand2l3 as Lente
(if child is <6yo, useNPH insteadof [-ente)
3. PM: 1/3 of total dosewith ll2 as Flumalogand l/2 as Lente
(if child is <6yo. useNPII insteadof I-ente)
The insulin drip sltould be discontinued 30-60 min after the first dose of subo
insulin
4. Adjust AM anclPM dosesdaily basedon fingerstickglucoselevels
until glucoselevelscomeinto the normalrange(70-l20rng/dl).
This may rcquireas much as 1.5u/kg/day(or more!) in the
hospital
IX.
Summary
The mortality rate of DKA in children,despiteall that we know, continuesto be 3-5%.
One must never be lulled into a "cookbook" approachto DKA. This referenceservesas
a guideline, not a protocol, for therapy. It does not replace an understandingof the
pathophysiologyunderlyingDKA, vigilant surveillance,and active modificationof the
treatmentto prevailingcircumstances.
DKA Guidelines
25-April-06