Guidelinesfor the Management of DiabeticKetoacidosis

Definitionof DiabeticKetoacidosis

D K A
II.

Hyperglycernia Ketonemia/ketonuria Acidosis Pathophysiolosy

Blood sugar> 200 mg/dl p H < 7 . 3o r I I C O j < l 5 n r E q / l -

Insulindeficiency hasthreemain effects: L Lossof insulin-dependent glucose transport into peripheral tissues gluconeogenesis 2. Increased in the liver 3. Increased breakdown of fat, protein,andglycogen Thus, insulin deficiency results in hyperglycemia(from increasedhepatic glucose prodttction and decreased peripheral uptake)and acidosis (primarily derivedfrom hepatic fatty acidoxidationinto ketoacids). Ilyperglycetnia abovethe renal threshold (>180-200mg/dl) resultsin glycosuria. This produces an osmoticdiuresisthat dragssolutes (Na, K, Cl, PO4)along with it, leadingto dehydrationand electrolytelosses. With significantdehydration,there may be poor perfusionof peripheraltissuesleadingto lactic acidosis,which further aggravates the existingketoacidosi s. I II. Assessmcnt A. History Tlte classic symptornsof new-onsetdiabetesmellitus are polyuria, polydipsia, and polyphagia accompanied by 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 progressive obtundationmay precipitatethe visit to the EmergencyDepartment. In children known to have diabetes, DKA is usuallypreventable.It is often precipitated by poor compliancewith the home managcmcnt routitrcor failureto increase insulindoses with an intercurrent illness. B. PhysicalExarn l. Airway -- may be compromised in patients with extremeobtundation.Consideration shouldbe given to intubationand mechanical ventilationif the patientis not making adecluate respiratory compensation for the metabolic acidosis.

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-- typically deep,hyperpneic (Kussmaul). Breathsoundsshouldbe clear; 2. Breathing rnay suggest intercurrent ralcs/rhonchi infectionor pulmonarycdema(lvhich can be seen in the correction of DKA). 3. Circulation-- particularattentionshouldbe paid to pulse,blood pressure, capillary refill, and any orthostaticchanges. Childrenwith DKA are hyperosmolar, so that intravascular flLridsare sparedat the expenseof cellular fluids. Therefore,the clinicalexatninatiotr underestimates the degree of dehyclration. 4. Mental status-- A lull neurological examination must be performedon all patients presentingin DKA, so that a baselinemay be established to which subsequent examinations may be compared. Acute deteriorations in menlal statusmay herald cerebral edema(seesectionon cercbral edema). 5. Abdonren -- many patients in DKA complain of abdominal pain, often due to persistentvomiting or ketosis. Tenderness tends to improve with treatment;pain which remainsor worsensshould prompt considcration processes of other disease (e.g., appendicitis). C. Initial laboratorytcsts The laboratory confirmation of thc cliagnosis of diabetes mellitus requires only a fingerstickblood sugar and urinalysisto confirm the hyperglycemia,glycosuriaand ketonuria, but in DKA additionallaboratory testsare useful in assessing the severityof illnessand guidingtreatment. 1. Electrolytes The sodium is typically low, as a result of urinary losses, (artefactual hyperglycenria, and hypertriglyceridemia hyponatremia). For every 100 above200 mg/dl,, the measure mgldL glucose Na shouldbe reduced by I .6 mEqil.
N&.u..".t.,I : + 1.6 N&,r'r.nrur.,r x

- 200 [Glucose] t00

Potassium may be low, normal, or elevated, but the total body storesare always depleted. Bicarbonatevalues are usually low, consistentwith metabolic acidosis. BUN and with dehydration. Creatinine areusuallyelevated Glucoseis invariablyelevated in DKA. 2. Venousblood gas -- will documentmetabolicacidosis. Arterial blood gas should alsobe considered in the appropriatc setting of severe clinical decompensation. -- Phosphate Calciunr.Phosphorus levels are usually low due to urinary losses. Iteplacement in the rehyclration of phosphate fluids nray precipitatetetanyin patients with low calcium levels. If the initial calcium and phosphorus levels are closeto normal,thereis no needto keeprepcating them.

3.

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4.

CBC w/ differential -- ElevatedWBC countsand "left shifts" are often seenwith the indicate an aoute infectiousprocess. acutc stressof DKA and do not necessarily significantinfectionmay be present evenin the absence of fever. Furthermore, testswill depend on the clinical situation. Additionallaboratory Goalsof Therapv

5. IV.

it is irnportant In planningtreatment, to consider the importantcomplications of DKA: collapse A. Cardiovascular 1. Fromdchydration involvesintravascular 2. Treatnrent fluid expansion with ISO'|ONIC fluids (saline) B. Overwhclmingacidosis l. From ketoacidproductionand lacticacid accumulation 2. Volurneexpansion and tissuereperfusion to oorrectlactic acidosis 3. Pronrptinitiationof insulinto stopfatty acid oxidationand ketoneproduction in patientswith arterial pH < 6.9 and/or 4. Consideruse of sodium bicarbonate evidence of myocardialdepression C. Ilypokalcmia with rapidintracellular l. lnsulin therapyis associated movementof potassium potassium 2. Adequate replacement 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 hyperosmolarity may lead to cerebral cellular just as the swellingand brain herniation. It usuallyoccurs6-18 hoursinto therapy, patient appears to be clinically and biochernically improving. This is the most contntoncauseo-f'mortaliqt in children with DKA !!! 3. Muclr of the etiology and pathophysiology of cerebral edemais still unknown,but the risk shouldbe niinimizedbv attention to the followins: (over48 hrs) with isotonicfluids a. Slorvfluid replacement monitoringand slow rise of calculated b, Irrequent CORRECTEDNa values for early signsof increased c. Close neurologicsurveillance ICP (headache, lethargy, slurredspeech, obtundation) and rapid evaluation & action

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V.

'Ireatment A. Initial Resuscitation Obviously, adequate airway patency and brcathing should be assessedfirst, and should always be made as needed. Initial fluid resuscitation immediateinterventions is potentially fluid replacement rapid Remember. witlr normal saline, 10-20 cclkg. of fluid needs should guide treatment,not so thotrghtfirl consideration dangerous, orthostatic l0-20 cclkg aliquot,pulse,blood pressure, After each "automatic"reaotions. The aim is perfusion, and blood glucose shouldall be reassessed. intake/output, changes, them. but to ittrprove normalizethe vital sigris lrot to completely B. Insulin (BG > 1000) The initial doseis usually 0.1 Units/kg/hour.For profoundhyperglycemia goal is to preferable. The may be Units/kg/hr) lower rates(0.05-0.75 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 steady dcclinein

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 . tl 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 nra-v D e x t r o s ec o n c e n t r a t i o n s 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 .

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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 cardiovascular dysfunction,such as poor contractilityor peripheral vasodilation The dosemay bc calcul:rte by the formula Dose(mliq): weight(kg) x 0.3 x (15 - [HCOr1) Alternatively, a reasonable doseis l-2 mEq/kg. Bicarbonate shouldalwaysbe 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 response to bicarbonate suggests inadequate volume status. respiratory compromise, or severe systemic infection(sepsis). Recentevidencehas called into questionthe utility of bicarbonate and administration. most studiesshorv that bicarbonate use 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. Calculations should aim to restorethe fluid deficit slowllr and evenly over 48 hours. The fluid replacement rate 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. Resuscitation fluids should be subtracted from the fluid deficit. Replacement of fluids for urinary lossesis not needed, bccause urinary losses are usually negligibleafter the first several hours of treatmcnt. THE RESUSCIT'ATION FLUID SHOULD ALWAYS BE NORMAL SALINE. Thereafter,normal saline and'/, normal saline can be used,although we prefer nonnal saline. Hypotonic fluid replacement increases the risk of cerebral edema. In prolbund hypernalremia, 213 or 3/4 NS may be considered after the hyperglycemia hasbeencorrected.

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E. Electroll'tcrcplacenrent 1. Sodium- Total body Na deficit of 8-10 mEq/kg as a result of osmoticdiuresis. are generallynot needed. The initial Calculationof dellcits and rcplacements rehydrationfluids in DKA should almost always be normal saline to protect changedto 3/a againstcerebraleclema, or t/znornlal salineas neededlater. -- 'l'otal body K cleficitof 8-l0 mEq/kg as a result of osmoticdiuresis. Potassium a acidemiacauses f-lor.vever. serllmK+ may be normalor evenelevated, because space. II+/K+ exchangethat rnoves K+ out of the cells into the intravascular of correctionof acidemiaand the direct ScrurnK+ falls r.viththerapy,because action of insulin on cellular K+ uptake. Potassiumshould be added to the replacenrent lluids as soonas the abscnce of renalfailureis shown:

2.

K+ < 3.0mEq/L K + : 3 . 0 - 6 . 0m E q / t , K+ > 6.0mEq/I.

60 mEq/L 40 mllq/L holdK

ratesas high as 80 mEq/L may be needed.Rates> 80 Occasionally, replacement mEq/L shouldbe given via centralvenousaccess. Potassium rates replacement greater than 0.5 mEq/kg/hrshouldbe avoided. Serumpotassium levelsshouldbe known beforeinsulin is given. FormalIIKG shouldbe considered in patients with < -' potassium levels 3.0 or 6.0 mEq/L. serum 3. Phosphate-- To correct phosphatedepletion, and to prevent hyperchloremia (rvhich often occurs during treatmentof DKA), the potassium is generally replaced as: Chloride* Potassium Potassium Phosphate, in a l:1 ratio This methodoffers the advantage of replacingphosphate, which improvesoxygen and energydelivery,throughthe formationof ATP and2,3-DPG. Calcium shouldbe monitoredwhen receivingsupplemental phosphate. ** If potassium phosphate is not available, standard KCI may still be given +* VI. Monitorins frequent Treatment of DKA requires eyes-on. hands-on, DKA brain-onreassessment. 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.

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A. Neurological reassessment q lhr shouldbe performed B. Blood glucose qlhr while on an insulin infusion shouldbe measured C. Electrolltesq2hr until calculated Na and K arenormal and measured HCO3> 15, then q4hr until infusionsare d/c'd. More frequent monitoringmay be necessary if the calculated Na falls at any time. D. BuN/Creatinine, calcium and phosphorus no more frequently than q4-6hrsunless clinically indiczrted. E. Serial measurements of arterial pl{ may be necessary in intubatedpatients,those with extreme life-threatening acidosis,or after bicarbonatetherapy. These patientsshould have intra-arterialcatheters placed and be monitored in the ICU. Serial VBG's may be discontinuecl onceHCOr > 15. F. All patients shouldbe 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 consultation arerequiredin this setting. VII. The Hieh-Risk Patient

Patients with the following characteristics may requireICU admission: A. B. C. D. E. F. G. H. Age<3years Significantly alteredor deteriorating mentalstatus pH<7.2 > 1000mg/dl Glucose > 160or any patientwith falling (calculated) Na (calculated) Na < K 3.5 mEq/L on admission > 350 mOsm) Severe (Sor,n hyperosmolality Otherorgansystemdysfunction that complicates treatment

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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 changcd to subcutaneous insulin afler tolerating oral nutrition well, and at a time of a major meal(breakfast or dinner). B. Subcutaneous insulin may also be starleddirectly in new onsetDM. if the patient is not in kctoacidosis. fbr initialdoses C. Guidelines as lbllows: l. Total dosefor day : 1.0unit/kglday 2. AM:213 of total dosewith ll3 as Humalogand2l3 as Lente (if child is <6yo, useNPH instead of [-ente) 3. PM: 1/3 of total dosewith ll2 as Flumalogand l/2 as Lente (if child is <6yo. useNPII instead of I-ente) The insulin drip sltould be discontinued 30-60 min after the first dose of subo insulin

4. Adjust AM anclPM doses daily basedon fingerstickglucose levels glucose until levelscomeinto 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, continues to be 3-5%. One must never be lulled into a "cookbook" approach to DKA. This referenceservesas a guideline, not a protocol, for therapy. It does not replace an understandingof the pathophysiology underlyingDKA, vigilant surveillance, and active modificationof the treatment to prevailingcircumstances.

DKA Guidelines

25-April-06