Diabetic Ketoacidosis in Children Keystone, July, 2008 Arleta Rewers MD, PhD Robert Slover MD.

Diabetic Ketoacidosis in Diabetic Ketoacidosis in ChildrenChildren

Keystone, July, 2008 Keystone, July, 2008

Arleta Rewers MD, PhDArleta Rewers MD, PhD

Robert Slover MDRobert Slover MD

OverviewOverview• Review the incidence and Review the incidence and

pathophysiology of DKApathophysiology of DKA• Define the role of patient self-Define the role of patient self-

monitoring including blood ketones monitoring including blood ketones testing and the healthcare testing and the healthcare professional advice in preventing professional advice in preventing DKA DKA

• Describe current approaches to the Describe current approaches to the clinical diagnosis of DKA, including clinical diagnosis of DKA, including the role of ketone body levels the role of ketone body levels

• List treatment options for DKAList treatment options for DKA

Definition Definition

• Hyperglycemia BG > 200 mg/dl (11 mmol/l) Hyperglycemia BG > 200 mg/dl (11 mmol/l) (young or partially treated children, pregnant adolescents (young or partially treated children, pregnant adolescents

may present with “euglycemic ketoacidosis”)may present with “euglycemic ketoacidosis”)

• Venous pH <7.3 and/or bicarbonate <15 Venous pH <7.3 and/or bicarbonate <15 mmol/Lmmol/L– mild DKA pH <7.3 bicarbonate <15 mild DKA pH <7.3 bicarbonate <15 – moderate pH <7.2 bicarbonate <10moderate pH <7.2 bicarbonate <10– severe pH <7.1 bicarbonate < 5severe pH <7.1 bicarbonate < 5

• Glucosuria and ketonuria/ketonemia (Glucosuria and ketonuria/ketonemia (β-HOB)β-HOB)

Incidence of DKA at onsetIncidence of DKA at onset

• Wide geographic variation in DKA rates Wide geographic variation in DKA rates at diabetes onset: 15 -70% at diabetes onset: 15 -70%

• More common in developing countriesMore common in developing countries

• DKA rates inversely related to DKA rates inversely related to incidence of type 1 diabetesincidence of type 1 diabetes

Diabetic Ketoacidosis at Diagnosis of DM Diabetic Ketoacidosis at Diagnosis of DM in Youth: in Youth: The SEARCH for Diabetes in Youth StudyThe SEARCH for Diabetes in Youth Study

Incidence of DKA at the time of diagnosisIncidence of DKA at the time of diagnosis • SEARCH is multicenter study SEARCH is multicenter study

• In 2002 began population-based In 2002 began population-based ascertainment of incident cases of DM in ascertainment of incident cases of DM in youth younger than 20 years youth younger than 20 years

• Incidence:Incidence:

• Overall - 25.5% (CI 23.9-27.1)Overall - 25.5% (CI 23.9-27.1)

• Type 1 - 29.4 % ( CI 27.5-31.3%)Type 1 - 29.4 % ( CI 27.5-31.3%)

• Type 2 - 9.7% ( CI 7.1-12.2)Type 2 - 9.7% ( CI 7.1-12.2)

Rewers A et al., Pediatrics, May 2008

Risk factors for DKA at onsetRisk factors for DKA at onset

• Age <12 yrsAge <12 yrs

• No first degree diabetic relativeNo first degree diabetic relative

• Lower socioeconomic statusLower socioeconomic status

• High dose glucocorticoids, atypical High dose glucocorticoids, atypical antipsychotics, diazoxide and some antipsychotics, diazoxide and some immunosuppresive drugsimmunosuppresive drugs

• Poor access to medical carePoor access to medical care

• UninsuredUninsured

Prevalence of hospitalization and Prevalence of hospitalization and DKA at onset DKA at onset Colorado children, 1978-2001Colorado children, 1978-2001

0%

20%

40%

60%

80%

100%

1978-82 n=305

1984-88 n=541

1998-01 n=606

% hospitalized% with DKA

p=0.038

p<0.00001

Rewers et al., ADA 2003

DKA in children with established DKA in children with established T1DMT1DM

• The risk of DKA varies from 1:10 to 1:100 /p-The risk of DKA varies from 1:10 to 1:100 /p-yr yr

• Poor metabolic control or previous DKA Poor metabolic control or previous DKA risk risk

• Adolescent girlsAdolescent girls

• Children with psychiatric disorders, Children with psychiatric disorders, including those with eating disordersincluding those with eating disorders

• Lower socio-economic status Lower socio-economic status

• Lacking appropriate insuranceLacking appropriate insurance

• Inappropriate interruption of insulin pump Inappropriate interruption of insulin pump therapytherapy

Predictors of Acute Complications in Children With Type 1 Diabetes

A Rewers, HP Chase, T MacKenzie, P Walravens, M RobackM Rewers, RF Hamman, G Klingensmith

2002;287:2511-2518

Cohort of 1,243 diabetic children from BDC - age 0-19 years - residence in the six-county Denver area - outpatient visits between 1/1/1996 - 1/1/2001

Average follow-up 3.2 yearsTotal follow-up 4,000 person-years

DKA events 320

DKA incidence 8 / 100 person-years

Incidence of DKA in established Incidence of DKA in established patientspatientsBDC Cohort, 1996-2001 BDC Cohort, 1996-2001

0

5

10

15

<7 7 to 12 >12

girlsboys

Incidence /100 p-yrs

Age [years]

p=0.006p=0.0006

p=0.06

Proportion of Children with Proportion of Children with Recurrent DKARecurrent DKA

• 60% of DKA 60% of DKA episodes episodes occurred in 5% occurred in 5% of children who of children who had 2 or more had 2 or more events events 0 1 2+

# of DKA events

5%

Diabetic KetoAcidosis (DKA)

1. 160,000 Admissions to private hospitals/year

2. Cost = over 1 billion $ annually

3. 65% = <19 years old

4. Main cause of death in children with diabetes (approximately 85%)

5. Cerebral edema in 69%

$0

$2,000

$4,000

$6,000

$8,000

$10,000

$12,000

with DKA w/out DKA

Cost of hospitalization of a diabetic patient

*HCIA-Sachs, 1998 Claims Data Warehouse, represents 2.5MM lives and 150 health plans

$11,123

$6,055

Diabetes Care 2006 29:1150-1159

Signs of DKASigns of DKA

• Vomiting Vomiting

• Increased urinationIncreased urination

• Abdominal painAbdominal pain

• Fruity odor to breathFruity odor to breath

• Dry mouth and tongueDry mouth and tongue

• DrowsinessDrowsiness

• Deep breathingDeep breathing

• ComaComa

• DeathDeath

Mortality in Children with Mortality in Children with DKADKA

• 0.15% USA0.15% USA

• 0.18% Canada0.18% Canada

• 0.31% UK0.31% UK

• 80% of deaths occurs in association with signs of 80% of deaths occurs in association with signs of CECE

• Other causes: Other causes: – hypokalemia / hyperkalemiahypokalemia / hyperkalemia– thrombosisthrombosis– intracranial bleeding, infarction intracranial bleeding, infarction – sepsis and other infections, e.g., mucormycosis sepsis and other infections, e.g., mucormycosis

– aspiration pneumoniaaspiration pneumonia– pulmonary oedema, ARDSpulmonary oedema, ARDS

Physical ExamPhysical Exam

• PerfusionPerfusion

• Vital Signs - including weightVital Signs - including weight

• HydrationHydration

• Mental StatusMental Status

• Evidence for insulin resistanceEvidence for insulin resistance

• Venous pHVenous pH

• BUNBUN

• Serum OsmolalitySerum Osmolality

• PhosphorusPhosphorus

• CalciumCalcium

• Anion GapAnion Gap

Initial Laboratory Initial Laboratory EvaluationEvaluation

Glucose*Glucose* Ketones*Ketones* SodiumSodium PotassiumPotassium ChlorideChloride HCO3HCO3

*Always perform in an ill child

CalculationsCalculationsSerum Osmolality:Serum Osmolality:

2[Na+K]+ (glucose/18) + BUN/2.82[Na+K]+ (glucose/18) + BUN/2.8

Serum Na:Serum Na:Corrected Na = Corrected Na =

measured Na + (measured Na + (1.61.6)(glucose - 100)/100)(glucose - 100)/100

Anion Gap:Anion Gap:

[Na] – ([Cl]+[HCO[Na] – ([Cl]+[HCO33])])Normally 12+/-2 mmol/LNormally 12+/-2 mmol/L

Cerebral EdemaCerebral Edema

Major cause of death in childhood DKA Major cause of death in childhood DKA – 20% with cerebral edema die20% with cerebral edema die– 20% with mild to severe neurologic 20% with mild to severe neurologic

outcomesoutcomes

• At risk:At risk:– Initial pH < 7.1Initial pH < 7.1– Baseline mental status abnormalBaseline mental status abnormal– Newly diagnosed, < 5 years oldNewly diagnosed, < 5 years old– Rapid rehydration (> 50cc/ kg in first 4 hrs)Rapid rehydration (> 50cc/ kg in first 4 hrs)– Hypernatremia/ persistent hyponatremiaHypernatremia/ persistent hyponatremia

Age distribution of affected Age distribution of affected childrenchildren

Time of onset of Neurological Time of onset of Neurological Compromise (hours)Compromise (hours)

0

2

4

6

8

10

12

14

16

0-2.9 3-5.9 6-8.9 9-11.9 12-14.9 >15

# ofpatients

Muir A, et al, Diab Care. July 2004

12-15

Timing of Onset of Cerebral Edema in DKA

Symptoms and signs of Symptoms and signs of cerebral edemacerebral edema

• HeadacheHeadache

• Decreased or worsening level of Decreased or worsening level of consciousnessconsciousness

• Slowing of the HR Slowing of the HR

• Increase in BPIncrease in BP

• Sudden onset/return of vomitingSudden onset/return of vomiting

• Warning signs occur before the onset Warning signs occur before the onset of CEof CE

Clinical Factors Associated Clinical Factors Associated with Cerebral Edemawith Cerebral Edema

• Prolonged IllnessProlonged Illness• Severe acidosis - low PA CO2Severe acidosis - low PA CO2• Severe dehydrationSevere dehydration• Bicarbonate therapyBicarbonate therapy• Persistent hyponatremiaPersistent hyponatremia• Excessive fluid admistrationExcessive fluid admistration

Cerebral edemaCerebral edema

• CE occurs in 0.3%- 1% of all episodes of CE occurs in 0.3%- 1% of all episodes of DKADKA

• Initial 24 hours of treatmentInitial 24 hours of treatment

• Younger children (< 4 yrs)Younger children (< 4 yrs)

• Delayed diagnosisDelayed diagnosis

• Greater dehydration and acidosis, lower Greater dehydration and acidosis, lower pCO2pCO2

• Insulin given before fluidsInsulin given before fluids

Etiology of CEEtiology of CE

• Vasogenic -Vasogenic - excessive accumulation of excessive accumulation of water and solutes in the interstitial space, water and solutes in the interstitial space, due to dysfunction of the blood-brain due to dysfunction of the blood-brain barrierbarrier

• Cytotoxic - Cytotoxic - excessive accumulation of excessive accumulation of water and solutes in the intracellular water and solutes in the intracellular space, due to dysfunction of cell-volume space, due to dysfunction of cell-volume regulatory mechanisms regulatory mechanisms

• Both forms may co-existBoth forms may co-exist

Excessive Free WaterExcessive Free Water

• Corrected Na = Na(measured)+1.6 Corrected Na = Na(measured)+1.6 (glucose-100)/100(glucose-100)/100

• Calculated sodium is low and falling in Calculated sodium is low and falling in many cases of cerebral edemamany cases of cerebral edema

• ADH levels rise 5-50 times in DKA and ADH levels rise 5-50 times in DKA and contribute to increase in free water contribute to increase in free water and hyponatremiaand hyponatremia

Cerebral EdemaCerebral Edema

• Know what to look forKnow what to look for– Altered mental status/ severe headacheAltered mental status/ severe headache– Recurrence of vomitingRecurrence of vomiting– Changes in pupil size, seizures, Changes in pupil size, seizures,

bradycardiabradycardia– Clinical worsening despite improving lab Clinical worsening despite improving lab

valuesvalues– CT/ MRI changes may not be seen in early CT/ MRI changes may not be seen in early

cerebral edemacerebral edema

Cerebral Edema Bedside Cerebral Edema Bedside ScoreScore

Muir Diab Care 2004 27:1541-46

Caveat – note that patient needs to be significantly affected to meet diagnostic criteria

Timing of presentation of cerebral edema

Treatment of cerebral Treatment of cerebral edemaedema

– Mannitol: 1 gram/ kg IV over 30 minutesMannitol: 1 gram/ kg IV over 30 minutes– Elevate the head of the bedElevate the head of the bed– Decrease IVF rate and insulin infusion Decrease IVF rate and insulin infusion

raterate– Pediatric ICU managementPediatric ICU management– Do not delay treatment until Do not delay treatment until

radiographic evidenceradiographic evidence

Diagnosis and prevention of Diagnosis and prevention of DKADKAin outpatientsin outpatients

Why do ketones develop?No carbohydrate intake

• fasting

• gastroenteritis

• Atkins diet, neonates fed high-fat milk

Prolonged exercise, pregnancy

Lack of insulin activity• onset of diabetes (insufficient secretion)

• interruption of insulin delivery in established pt

Increase in insulin resistance• infection, illness, surgery, stress

Alcohol, salicylate ingestion, inborn metabolic errors

Treatment of Mild DKA to Prevent Progression: Key: Early Detection

Check blood ketones (-OHB) for a person with diabetes any time:

1) A SMBG is >300 mg/dL (16.7 mmol/L)

2) An illness or infection is present

3) Unusual symptoms are present

4) It is realized a shot/bolus was missed or bad insulin

Old Paradigm: Check urine ketones

New Paradigm: Check blood -OHB

1) Blood -OHB tells you how you are doing at the time of the test. (Urine may have been in bladder for hrs)

2) Urine ketone levels may not accurately reflect the severity of the ketonemia

3) A person may not be able to void

4) Some (teens) give false urine test results

Hand-held deviceHand-held deviceAbbott/MediSenseAbbott/MediSense

The results are The results are notnot real time real time

The readings are qualitative: color comparisons indicating The readings are qualitative: color comparisons indicating

high, medium or low levelshigh, medium or low levels

Short shelf life (typically 90 days on opening a vial)Short shelf life (typically 90 days on opening a vial)

Sulfhydryl drugs, including the ACE inhibitor, Captopril, Sulfhydryl drugs, including the ACE inhibitor, Captopril,

may cause false-positive resultsmay cause false-positive results

High doses of Vitamin C may cause false-negative results High doses of Vitamin C may cause false-negative results

Method does not detect the major ketone body Method does not detect the major ketone body --

hydroxybutyratehydroxybutyrate

Disadvantages to Urine Ketone Testing

Interpretation of Blood -OHB

-OHB level (mmol/L):

< 0.6 = normal >1.0 = hyperketonemia

0.6-1.0 = take extra insulin + fluids

1.0-1.5 = as above; recheck in 1 hr and, if no improvement, call diabetes provider

1.5-3.0 = call diabetes provider STAT

> 3.0 & sick = KETOACIDOSIS > Go to ED

• 123 participants, age 3–22 years 123 participants, age 3–22 years

– 61 randomized to home blood 61 randomized to home blood ß-ß-OHB testingOHB testing

– 62 randomized to home urine Ketostix62 randomized to home urine Ketostix® testing® testing

• All participants trained on their sick-day guidelinesAll participants trained on their sick-day guidelines

• OutcomesOutcomes

– ER visitsER visits

– HospitalizationsHospitalizations

Laffel L, et al. Diabet Med 2005

Sick Day Management: A Randomized Clinical Trial

Laffel L, et al. Diabet Med 2005

Patients who monitor blood ß-OHB test more often

than those who test for ketonuria

Lower incidence rates of ER use/hospitalizations in patients using blood ß-OHB monitoring vs. Ketostix

6-month follow-up

p = 0.05

Laffel L, et al. Diabet Med 2005

Use of Blood Use of Blood -hydroxybutyrate -hydroxybutyrate Levels at the BedsideLevels at the Bedside

During Treatment of DKADuring Treatment of DKA

ADA, June, 2007ADA, June, 2007

Normal statepostprandial

glucose

acetyl CoA

Fat

pyruvate

Krebs cycle

oxaloacetate

citrateEnergy

Normal statepostprandial

glucose

fatty acids (+ glycerol)

acetyl CoA

Fat

lipase

fatty acyl CoA

pyruvate

Krebs cycle

oxaloacetate

citrate

-oxidation

insulin

Energy

Energy

Normal statepostprandial

fatty acids (+ glycerol)

acetyl CoA

acetoacetate

acetone -OHB

Fat

lipase

fatty acyl CoA

Krebs cycle acetoacetyl CoA

-oxidation

HMGCoA synthase

1:1

insulin

Energy

Energy

Energy

Ketosis in DKA- alternative source of energy

glucose fatty acids

acetyl CoA

acetoacetate

acetone -OHB

Fat

lipase

fatty acyl CoA

pyruvate

Krebs cycle

oxaloacetate

citrate

acetoacetyl CoA

-oxidation

HMGCoA synthase

1:10

insulin

glucagon

Energy

Energy

Energy

Is bedside β-OHB monitoring using Is bedside β-OHB monitoring using hand-held device as accurate as hand-held device as accurate as reference laboratory method ?reference laboratory method ?

Bedside meter β-OHB [mmol/L]

Laboratory reference β-OHB [mg/dL]

Correlation between venous whole blood Correlation between venous whole blood ββ-OHB levels measured using -OHB levels measured using Precision Xtra™ and serum levels using Cobas Mira Plus (Roche)Precision Xtra™ and serum levels using Cobas Mira Plus (Roche)

Rewers A et al. Diabet Technol Therapeutics, 2006;8:671

Bland-Altman plot showing good agreement between Bland-Altman plot showing good agreement between ββ-OHB levels -OHB levels measured using Precision Xtra™ and Cobas Mira Plus (Roche)measured using Precision Xtra™ and Cobas Mira Plus (Roche)

Mean difference = 0.18 (C.I. -1.18-1.53)Mean difference = 0.18 (C.I. -1.18-1.53)

Rewers A et al. Diabet Technol Therapeutics, 2006;8:671

also

Byrne H, et al. 2000; Wallace TM, et al. 2001

Ham MR, et al. 2004; Khan ASA, et al. 2004

CONCLUSIONCONCLUSION

Real-time bedside measurement ofReal-time bedside measurement of --OHB is generally as accurate as OHB is generally as accurate as reference laboratory, especially at levels reference laboratory, especially at levels up to 3.0- 4.0 mmol/Lup to 3.0- 4.0 mmol/L

Is capillary blood β-OHB Is capillary blood β-OHB monitoring superior to testing monitoring superior to testing

urine for ketones ?urine for ketones ?

Measurement of KetonesMeasurement of Ketones

• Urine ketone measurements use a “dip stick” method Urine ketone measurements use a “dip stick” method based on a chemical reaction with based on a chemical reaction with acetoacetateacetoacetate. E.g.,. E.g., ChemstripChemstrip®® from Rochefrom Roche; ; ClinistixClinistix®®, , KetostixKetostix®® , , Keto-DiastixKeto-Diastix®® from Bayer)from Bayer)

• Blood ketone testing that specifically measures Blood ketone testing that specifically measures ß-ß-hydroxybutyratehydroxybutyrate are available for use in the are available for use in the laboratorylaboratory (e.g., Sigma(e.g., Sigma®®, Cobos, Cobos®® from Roche) from Roche) and a and a hand-held meter (Abbott / MediSense)hand-held meter (Abbott / MediSense)

Blood β-OHB testing is superior to Blood β-OHB testing is superior to urine ketone testing in urine ketone testing in detecting ketosisdetecting ketosis

SensitivitySensitivity SpecificitySpecificityPositive Positive

predictive valuepredictive valueNegative Negative

predictive valuepredictive value

KetonuriaKetonuria 63%63% 100%100% 100%100% 72%72%

Capillary blood Capillary blood β-OHB β-OHB

80%80% 100%100% 100%100% 83%83%

Guerci B , et al. Diabetes Care 2003

Similar data: Taboulet P et al. Eur J Emerg Med 2004

Gold standard – plasma β-OHB by reference laboratory method

(KONE Delta Automatic Analyzer)

Advantages Blood β-OHB vs.Urine Ketone Testing

-OHB is a better marker of ketosis than acetoacetate

-OHB is ‘real-time’ while ketonuria is usually ‘old news’

• Ketonuria doesn’t accurately reflect severity of ketonemia

• A dehydrated person may not be able to void

• Some people are too ill or exhausted to do the urine test

• Some patients (teens) give false urine sample

• Urine ketone strips spoil after opened >6 months

Schade DS, Eaton RP Special Topics in Endo and Metab 1982;4:1-27

-hydroxybutyrate is a better indicator of metabolic status when detecting and treating DKA

β-OHBβ-OHB in diagnosis of DKA in diagnosis of DKAin EDin ED

β-OHB helps to diagnose DKA in patients with β-OHB helps to diagnose DKA in patients with known or new diabetes seen in ERknown or new diabetes seen in ER

PatientsPatientsStudyStudy

NNBloodBloodβ-OHBβ-OHB[mmol/[mmol/L]L]

SensitiviSensitivityty

SpecificitSpecificityy PPVPPV NPVNPV

BG>200, BG>200, adultsadultsBektas, 2004Bektas, 2004

139139 >0.42>0.42 72%72% 82%82%

Diabetic Diabetic childrenchildren

Ham, 2004Ham, 2004

5555 >1.5>1.5 85%85% 100100%%

BG>250, BG>250, age>18age>18

Nauheim, Nauheim, 20062006

160160 >1.8>1.8 91%91% 92%92% 86%86% 95%95%

BG>200, age BG>200, age >15>15

Harris,2004Harris,2004

5050 >2.0>2.0 >3.0>3.0

100%100%100%100%

85%85%88%88%

60%60%64%64%

100100%%

100100%%

Prisco F, et al. Pediatr Diabetes 2006

7.25

3

Capillary blood β-OHB vs. venous pH in 118 newly diagnosed children

DKA no DKA

compensated

acidosis

0.5

Can bedside β-OHB monitoring Can bedside β-OHB monitoring replace repeat measurements replace repeat measurements

of pH, bicarbonate and pCO2 of pH, bicarbonate and pCO2 during treatment of DKA?during treatment of DKA?

Correlation between baseline β-OHB and other Correlation between baseline β-OHB and other biochemical indicators in 68 children with DKA biochemical indicators in 68 children with DKA Pearson Pearson correlation coefficients (p <0.05 for all) correlation coefficients (p <0.05 for all)

Rewers A et al. Diabet Technol Therapeutics, 2006;8:671

Biochemical Biochemical indicatorindicator

Bedside meterBedside meter Reference Reference methodmethod

pHpH -0.63-0.63 -0.74-0.74

BicarbonateBicarbonate -0.74-0.74 -0.80-0.80

pCOpCO22 -0.55-0.55 -0.61-0.61

GlucoseGlucose 0.570.57 0.630.63

BUNBUN 0.350.35 0.420.42

Time series analysis showing that bedside β-OHB Time series analysis showing that bedside β-OHB levels correlated very closely with time-dependent levels correlated very closely with time-dependent levels of venous blood gaseslevels of venous blood gases

Rewers A et al. Diabet Technol Therapeutics, 2006;8:671

Biochemical Biochemical indicatorindicator

Bedside meterBedside meter Reference Reference methodmethod

pHpH β -6.3 ** β -6.3 ** β -8.0 **β -8.0 **

BicarbonateBicarbonate β -0.22 **β -0.22 ** β -0.24 **β -0.24 **

pCOpCO22 β -0.04 *β -0.04 * β -0.05 **β -0.05 **

* p<0.001; ** p<0.0001

CONCLUSIONCONCLUSION

While the initial measurement of pH, While the initial measurement of pH, bicarbonate and pCObicarbonate and pCO2 2 is warranted, real-is warranted, real-

time bedside measurement oftime bedside measurement of -OHB -OHB may replace repeat measurements of may replace repeat measurements of blood gases in treatment of DKAblood gases in treatment of DKA

Can bedside β-OHB monitoring Can bedside β-OHB monitoring shorten duration of shorten duration of

DKA treatment ?DKA treatment ?

Prisco F, et al. Pediatr Diabetes 2006;

In most newly-diagnosed children with ketosis, In most newly-diagnosed children with ketosis, capillary ketonemia resolves sooner than capillary ketonemia resolves sooner than ketonuriaketonuria

N =99

In children with DKA, capillary ketonemia resolves In children with DKA, capillary ketonemia resolves on average 11 hours sooner than ketonuria on average 11 hours sooner than ketonuria (n=40)(n=40)

Noyes KJ, et al. Pediatr Diabetes 2007, confirming Vanelli M, et. Al. Diabetes Care 2003

Example of an individual treatment profile

pH >7.3

β-OHB <1.0

pH >7.3

No ketonuria

β-OHB i.v. insulin U kg/h

CONCLUSIONSCONCLUSIONS

Real-time bedside measurement ofReal-time bedside measurement of --OHB may help to optimize treatment of OHB may help to optimize treatment of DKA and shorten the duration of DKA and shorten the duration of hospitalization hospitalization

• Venous pHVenous pH

• BUNBUN

• Serum OsmolalitySerum Osmolality

• PhosphorusPhosphorus

• CalciumCalcium

Initial Laboratory Initial Laboratory EvaluationEvaluation

Glucose*Glucose* Ketones*Ketones* SodiumSodium PotassiumPotassium ChlorideChloride HCO3HCO3

*Always perform in an ill child

TreatmentTreatment

MonitoringMonitoring

• Management requires close attention Management requires close attention to detailto detail

• Use a flowsheet to track vital signs Use a flowsheet to track vital signs labs, rates of insulin, fluids, dextroselabs, rates of insulin, fluids, dextrose

• Neurological statusNeurological status– consider neuro checks q 1 hr consider neuro checks q 1 hr – How does the patient look TO YOU?How does the patient look TO YOU?

• Assess, reassess and then assess againAssess, reassess and then assess again

TreatmentTreatment

• Consider ICU admission for closer Consider ICU admission for closer monitoring if:monitoring if:– Severe DKA (pH < 7.1 or < 7.2 in young Severe DKA (pH < 7.1 or < 7.2 in young

child)child)– Altered level of consciousnessAltered level of consciousness– Under age of 5 yearsUnder age of 5 years– Increased risk for cerebral edemaIncreased risk for cerebral edema

• Caution with meds that may alter mental Caution with meds that may alter mental statusstatus

Fluid Therapy for DKAFluid Therapy for DKA

• Assume 10-15% dehydrationAssume 10-15% dehydration

• Begin with a 10-20 ml/kg bolus of Begin with a 10-20 ml/kg bolus of NSNS

• Replace calculated deficit evenly Replace calculated deficit evenly over 36 hours - generally 1.5 x over 36 hours - generally 1.5 x maintenance for the next several maintenance for the next several hours is appropriatehours is appropriate

• Do not exceed 40ml’s/kg in the Do not exceed 40ml’s/kg in the initial 4 hours, or 4 L/m squared in initial 4 hours, or 4 L/m squared in 24 hours24 hours

DKA - FluidsDKA - Fluids

• Double bag systemDouble bag system– ¾ NS at 1.5 x M until glucose below 300 mg/dl¾ NS at 1.5 x M until glucose below 300 mg/dl– D10 ¾ NS to be mixed with ¾ NS to achieve D10 ¾ NS to be mixed with ¾ NS to achieve

desired glucose concentrationdesired glucose concentration

– K supplementationK supplementation

20mEq/L K Acetate + 20mEq/L K Phosphate20mEq/L K Acetate + 20mEq/L K Phosphate– Ionized calcium is low, phosphorous should not Ionized calcium is low, phosphorous should not

be givenbe given– early replacement and frequent monitoringearly replacement and frequent monitoring

– Bicarbonate therapy is rarely, if ever, indicatedBicarbonate therapy is rarely, if ever, indicated

Insulin Therapy for DKAInsulin Therapy for DKA • IV infusion with basal rate 0.1 U/kg/hrIV infusion with basal rate 0.1 U/kg/hr

• No initial insulin bolusNo initial insulin bolus – it will decrease time to – it will decrease time to correction of the glucose, but does not alter the correction of the glucose, but does not alter the time to correction of acidosistime to correction of acidosis

It may decrease the serum osmolality more It may decrease the serum osmolality more rapidly than desirablerapidly than desirable

• Ideal glucose decline is about 100 mg%/hrIdeal glucose decline is about 100 mg%/hr

• Continue insulin until urinary (blood) ketones Continue insulin until urinary (blood) ketones are clearedare cleared

PotassiumPotassium

• Add potassium when K< 5 and with Add potassium when K< 5 and with urinationurination– K >5.5 – no potassium in IVFK >5.5 – no potassium in IVF– K 4.5 – 5.5 – 20 meq/L K+K 4.5 – 5.5 – 20 meq/L K+– K <4.5 – 40 meq/L K+K <4.5 – 40 meq/L K+

Phosphate – the controversyPhosphate – the controversy

• Prevent depletion of RBC 2,3 DPG Prevent depletion of RBC 2,3 DPG which will improve tissue which will improve tissue oxygenation as acidosis is resolvingoxygenation as acidosis is resolving

• May be useful in patients with May be useful in patients with anemia, CHF, pneumonia, hypoxiaanemia, CHF, pneumonia, hypoxia

Use of Bicarbonate in DKAUse of Bicarbonate in DKA

• Bicarbonate should be used only Bicarbonate should be used only when when

there is severe depression of the there is severe depression of the

circulatory system or cellular circulatory system or cellular metabolism...metabolism...

• Not recommended unless pH <7.0, Not recommended unless pH <7.0, not even then, unless above truenot even then, unless above true

DKA: CasesDKA: Cases

• 12 year old admitted with:12 year old admitted with:– pH = 7.0pH = 7.0– Na= 136, K=3.8, glucose 583mg/ dlNa= 136, K=3.8, glucose 583mg/ dl– She is oriented and conversant on admission, She is oriented and conversant on admission,

you follow the DKA protocol, you follow the DKA protocol,

• 2 hours later she becomes difficult to 2 hours later she becomes difficult to arouse and is responsive only to deep pain. arouse and is responsive only to deep pain. - What do you do?- What do you do?

• Presume cerebral edemaPresume cerebral edema– Decrease fluid infusion to insensible losses Decrease fluid infusion to insensible losses – Give mannitol: 1 gm/kgGive mannitol: 1 gm/kg

DKA: CasesDKA: Cases

• 6 y/o boy is admitted in severe DKA. 6 y/o boy is admitted in severe DKA. The family has been traveling and he The family has been traveling and he has been ill for several days. has been ill for several days.

• Initial pH=7.0, K+ = 3.7, glucose is Initial pH=7.0, K+ = 3.7, glucose is 350mg%.350mg%.

• Despite replacement, his K+ now is 1.9 Despite replacement, his K+ now is 1.9 mg/dl - what do you do?mg/dl - what do you do?

• A “bolus” of potassium at TCH is A “bolus” of potassium at TCH is actually an infusion over an hour. An actually an infusion over an hour. An actual bolus of potassium into a central actual bolus of potassium into a central vein may be lethalvein may be lethal

DKA: CasesDKA: Cases

• 16 year old boy is admitted in 16 year old boy is admitted in moderate to severe DKA (pH=7.23), moderate to severe DKA (pH=7.23), his weight is 230 lbs, his BG is 1400, his weight is 230 lbs, his BG is 1400, serum osm is 360 mOsm/L, what do serum osm is 360 mOsm/L, what do you do?you do?

• Monitor! Everything you can!Monitor! Everything you can!

Successful ManagementSuccessful Management

• Careful attention to detailCareful attention to detail• Careful record keepingCareful record keeping

– A detailed flow chart is essentialA detailed flow chart is essential– Following the data recorded is also Following the data recorded is also

essentialessential

• Repeated examination of the Repeated examination of the patientpatient