2. GOALS
⢠REVIEW TYPE 1
DIABETES AND
METABOLISM AS
THEY RELATES TO
DKA
⢠CLINICAL DIAGNOSIS and MISLEADING
LABS
⢠TREATMENT and CONTROVERSIES
⢠TREATMENT GUIDELINES
3. Type 1 DM
⢠Autoimmune destruction
of the pancreatic islet
cell
⢠Hallmark = lymphocytic
infiltration of islets
⢠Progresses over years
⢠Leads to insulin
deficiency
⢠Later may be associated
with glucagon
deficiency as well
4. Progression to Type 1 DM
Autoimmune destruction
Honeymoon
100% Islet loss
âDiabetes thresholdâ
6. âTypicalâ SettingâŚ..
⢠9 yo boy presents to clinic with CC â 6 day history
of stomach pain and diarrhea.â âVomiting started 2
days ago and has persisted.â
â (+) weight loss
â PE: HR 140, RR 28, T97.8 Weight: 27 Kg
⢠Tachy mucous membranes
⢠Abd - soft, (+)BS, mild left CVA tenderness
â DX: viral gastroenteritis with mild dehydration
⢠Returned to ER 24 hours later
â PE: cachectic, quiet, tired, cooperative, (+) ketotic breath
7. Background
⢠15-30% of new diabetics present in DKA
â < 4 yrs of age = 40% with DKA @ diagnosis
⢠Most common cause of death in diabetics
less than 20 years of age
â 70% of related deaths in diabetics less than 10
yrs of age
⢠Mortality: 5-15% (1-2% at MEDCEN)
⢠Preventable
9. Etiology
⢠Results from inadequate insulin
â Accidental or intentional omission
â Inappropriate intervention when stressed
10. Etiology
² DKA violates rules of common sense
⢠Increased insulin requirement despite decreased
food intake
⢠Marked urine output in setting of dehydration
⢠Catabolic state in setting of hyperglycemia and
hyperlipidemia
11. Pathophysiology
Counter-Regulatory Hormones
⢠Insulin Deficiency is the Primary defect
⢠Stress hormones accelerate and exaggerate
the rate and magnitude of metabolic
decompensation
Pathophysiology Hormone
⢠Impaired insulin secretion Epi
⢠Anti-insulin action Epi, cortisol, GH
⢠Promoting catabolism All
⢠Dec glucose utilization Epi, cortisol, GH
12. Islets of β-cell destruction Insulin Deficiency
Langerhans
l
Ep i,Cortiso Decreased Glucose Utilization &
Stress GH Increased Production
Muscle
Adipo- Amino Glucagon
Increased Liver
cytes Acids Protein
Catabolism Increased
Ketogenesis
FattyAcids Gluconeogenesis,
IncreasedLipolysis Glycogenolysis
Polyuria Threshold
180 mg/dl Hyperglycemia
Volume Depletion
Ketoacidosis
Ketonuria
HyperTG
23. Misleading Labs
Sodium
⢠Triglycerides also artificially lower Na
Lipid Lipid
Na Na Na
Na Na Na
Serum Na Na
Na Na Na Gluc Na
Na Gluc
24. Misleading Labs
Potassium
⢠Acidosis leads to flux of K+ out of cells as H+
enters cells to buffer
⢠Dehydration and volume depletion
â Aldosterone ² Na reabsorption and K+
wasting
² Serum K+ usually normal or high, but total
body K+ is low
25. DKA- Risks of Therapy
Hypokalemia/Hyperkalemia
⢠With insulin therapy
â K+ moves into cells (1 meq/L / 0.1 unit pH )
⢠Even with K+ you must
â Give large doses (40 meq/L) K+
â Monitor K+ levels and EKG
⢠High K - tall peaked T, long PR, wide QRS
⢠Low K - depressed ST, diphasic T, Prom U-wave
â Cardiac dysrythmia
26. Misleading Labs
Ketones
⢠In the absence of insulin,
FFA go to the liver, and Nitroprusside
reaction
into mitochondria via
carnitine
⢠Ă-oxidation excess
acetylCoA
⢠Acetyl-CoA condenses to acetoacetate
⢠Insulin prevents utilization of acetoacetate
⢠so levels and shunt to Ă-hydroxybutyrate and acetone
27. Misleading Labs
Screening for Ketonemia
⢠Urine Dip stick vs. anion gap/serum bicarb
Sensitivity Specificity
DKA 99 % 69 %
² Diabetic with minor signs and symptoms
and negative urine ketone dip stick is
unlikely to have acidosis
= high negative predictive value for
excluding DKA
Am J Emer Med 34: 1999
28. Misleading Labs
WBC count
⢠N = 247 DKA admissions over 6 years
â Mean WBC = 17,519/mm3 (+/- 9,582)
â 69% without infection
â 17.8% presumed viral infection
â 12.9% bacterial infection - more common in
children < 3 years of age
² All need to be evaluated and re-evaluated if
persistent acidosis
Am J Emer Med 19: 270-3, 2001
30. Controversies and Risks of Therapy
⢠Fluids - composition, bolus
amount and total fluids/day
Cerebral
⢠Use of Bicarbonate
Edema
⢠Phosphate replacement
31. DKA â Controversy
Cerebral Edema - Truths ?
Acute
⢠Idiogenic osmoles in
CNS accumulate fluid
⢠Cerebral edema â
present in 100% of
patients prior to therapy
⢠Treatment exacerbates
cerebral edema
â Vigorous fluid
administration Late
Sequelae
â Hypotonic fluids
â Bicarbonate
32. DKA â Cerebral Edema
Actualities
â˘Etiology is not known
â˘Occurs exclusively in pediatric patients
â˘Mortality Rate = 21%
â˘Morbidity Rate = 27% (permanent neurologic
sequelae)
² Difficulty is relatively rare occurrence (1-3 %)
with subsequent small numbers of patients in
retrospective or prospective studies
33. DKA â Cerebral Edema
Actualities
⢠NEJM - Jan 2001
â N = 6977 DKA patients from 10 centers over 15
years
â 61 developed cerebral edema (0.9%)
⢠Pediatrics - Sep 2001
â N = 520 DKA patients over 5 1/2 years
â 2 developed cerebral edema
34. DKA â Cerebral Edema
Total Fluids
⢠> 4 L/m2/day, or > 50 ml/kg in first 4 hrs ι
JCEM 85:509-513, 2000 J Peds 113:10-14, 1988
hyponatremia Îą herniation
â May occur in patients that receive less
â Of 52 patients with neurologic
complications 21 had either a rise of serum
Na or fall less than 4 mmol/L
² Attention to fluid rate and tonicity is essential, but
may not be sufficient to predict subset that will
develop neurologic complications
35. DKA â Cerebral Edema
Total Fluids
⢠> 4 L/m2/day, or > 50 ml/kg in first 4 hrs ι
JCEM 85:509-513, 2000 J Peds 113:10-14, 1988
hyponatremia Îą herniation
â May occur in patients that receive less
â Of 52 patients with neurologic
complications 21 had either a rise of serum
Na or fall less than 4 mmol/L
² Attention to fluid rate and tonicity is essential, but
may not be sufficient to predict subset that will
develop neurologic complications
36. DKA â Cerebral Edema
Variable Time of Onset
# of Children with Neurologic Deterioration
7
Prior to therapy; longer duration
6 symptoms before diagnosis
5
4
3
2
NEJM 344:264-69, 2001
1
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 21 25
Hours after Initiation of Therapy
37. DKA â Cerebral Edema
Other
⢠Hypoxemia
â Childrenâs brains have higher oxygen
requirement, 5.1 mL/100g vs. 3.3 mL/100g
â Hypophosphatemia with resultant decreased
2,3-DPG decreases O2 delivery to brain cells
â Mannitol - earliest effects are related to
decreased viscosity, not to shift of fluid
from extravascular space
Neurosurg 21: 147-156, 1987
38. DKA â Cerebral Edema
Signs and Symptoms
1. Sudden and persistent drop in heart rate
- not bradychardia - not assoc with HTN
- not related to hydration status
2. Change in sensorium 7. Fall in serum
3. Headache Na, or failure
4. Emesis to rise
5. Incontinence
6. Unexplained tachypnea
JCEM 85:509-513, 2000
39. DKA â Cerebral Edema
Evaluation
⢠CT may be non-diagnostic at time of
symptoms
â 9 of 30 - no edema, 6 read as normal
â 5 of 9 - 2.5 to 8 hours after onset of coma, read as
normal
² Cerebral Edema is a clinical diagnosis.
Need to treat BEFORE imaging.
JCEM 85:509-513, 2000
40. DKA â Risks of Therapy
Bicarbonate Administration
⢠Administration to acidotic patient generates
rapid rise in CO2
⢠CO2 enters CNS rapidly
⢠HCO3- is delayed by blood-brain barrier
⢠Increased CNS CO2 exacerbates cerebral
acidosis
CO2 + H2O H2CO3 H+ + HCO3-
⢠May also reduce partial pressure of O2 in CSF
41. DKA â Risks of Therapy
Bicarbonate Administration
⢠Multi-center study from 10 pediatric centers, USA
and Melbourne, Australia over 15 yr period
â 6977 DKA hospitalizations: 61 cases cerebral edema
(0.9%)
⢠Presentation: PaCO2 BUN Glucose Bicarb
Cerebral Edema 11.3 27 758 23/61 (32%)
Controls 15.1 21 700 43/174 (23%)
â â fluid, insulin, or sodium administration, nor rate
of fall in glucose was associated
NEJM 344:264-269, 2001
42. **** ****
****
DKA â Risks of Therapy ****
**** ****
********
Bicarbonate Administration
⢠Variations in treatment exacerbate an on-going
pathologic process
⢠Brain ischemia is major underline etiology
â Hyperglycemia increases extent of neurologic damage
â Extreme dehydration, hypocapnia
â Concept of idiogenic osmotically active substances not
supported (no relationship to change in glucose, rate of
fluid or Na administration)
² Risk related to duration and severity of DKA
NEJM 344:264-269, 2001
43. DKA- Controversy
Phosphate
Theoretical
⢠Essential phosphate deficit
⢠W/treatment serum phosphate and 2,3-DPG fall
⢠Shift oxyhemoglobin curve reducing O2 deliver
Practical
⢠No evidence of direct benefit, but less Cl-
⢠Give ½ K+ replacement as K-phos x 8 hours
⢠Limit to 2 mEq/kg/day to avoid hypocalcemia
Endo Met Clin 29:Dec 2000
45. Elements of Therapy
⢠Fluids â treat shock, then sufficient to
reverse dehydration and replace ongoing
losses (will correct hyperglycemia)
⢠Insulin â sufficient to suppress ketosis,
reverse acidosis, promote glucose uptake
and utilization (will stop ketosis)
⢠Electrolytes â replace profound Na+ and K+
losses
46. Typical Therapy - Fluids
⢠10% dehydration is standard estimate (use
vweight if known)
â Bolus: treat shock, usual 20-30cc/kg
given 10cc/kg at a time
â Replace deficit over 48-72 hours
â ie. 10 % in 20 Kg pt = 2000ml over 48hrs
= maintenance + 42cc/hr x 48 hours
47. Typical Therapy - Fluids
⢠Use ½ NS to NS
⢠Average = 2 x maintenance
â 4:2:1 cc/kg/hr or 100:50:20 cc/kg/day
â ie. 25 kg patient
⢠(4 x 10) + (2 x 10) + (1 x 5) = 65 cc/hr
⢠(100 x 10) + (50 x 10) + (20 x 5)/24 hours
= 66.7 cc/hr
48. DKA â Risks of Therapy
Insulin
100%
Biological
0.1 units/kg/hr
effect
Current therapy uses
continuous insulin drip 100 uU/ml
² Drop glucose Insulin Level
50-100 mg/dl/hr
49. Typical Therapy - Insulin
⢠0.1 unit/kg/hr continuous drip (regular)
â Flush tubing with 50 ml
â 250 units regular in 250 cc NS (1.0 units/
ml)
= 0.1 u/kg/hr = 0.1 ml/kg/hr
50. Typical Therapy
Glucose - 2 Bag Method
⢠Goal - decrease blood glucose by 50-100
mg/dl/hr
⢠Must continue insulin therapy to correct
acidosis
⢠Order D10 NS to bedside
â when serum glucose < 300: add D5NS ( = 1/2
D10NS + maintenance bag)
â when serum glucose < 200: Change to D10NS
51. Typical Therapy
⢠K+ 40 meq/L (split between KCl and
Kphos)
⢠Reverse insulin resistance
â Treat infection
â Treat underlying illness - stress
⢠Bicarb - only if severe circulatory failure
and high risk of cardiac decompensation
from profound acidosis
52. Monitor
⢠ICU - pH < 7.3 and/or HCO3 < 15
⢠Available staff
⢠Strict I/O (NPO)
â Fluid calculations must account for ongoing
losses â vomiting, diarrhea, excessive urine
â ? If > 4 L/m2/day
⢠CNS activity - headache, change in
sensorium
53. Monitor
⢠Vitals - sudden drop in HR, tachypnea
⢠Neurologic checks - q30-60 minutes
⢠Weight - bid
⢠Labs
â dstick q1 hour
â Urine dip q void - resolution of ketonuria may
lag behind clinical improvement
54. Monitor
⢠Labs
â Lytes, VBG q 2-4 hours
² Drop in Na - increase risk of cerebral edema, ?
SIADH vs. cerebral salt wasting
² HCO3- / pH in first 2-3 hours may drop further due
to re-perfusion of tissue, lactic acidosis
55. DKA
Guidelines
⢠Common ground to start from
⢠Does not eliminate need to individualize
therapy
⢠Large deviations should be an opportunity
to critically review clinical and therapeutic
course
56. DKA
Flowsheet
⢠CIS is not a flow sheet, but rather a
database
⢠Inability to review all data at one time
decreases ability to make sound decisions
⢠Maintenance of flowsheet is the first step
in critical analysis of response to therapy
57. 9 yo lab Evaluation
⢠27 Kg - assume 10% dehydrated
⢠148| 109| 32 16.8 518
700 24.4
5.6 | <5 | 1.4 47.5
⢠Anion Gap = ⢠Fluid Def =
⢠Osm = ⢠Maintenance =
⢠Corrected Na = ⢠IV rate (24hrs) =
58. Transport of Patient with DKA
⢠2 large bore PIV
⢠Must have documentation of previous
treatments
â PE with vitals and notes on mental status
â Fluids - bolus and current
â ? SQ Insulin given - time and amount
â Contact phone number for labs/cultures
⢠Must have glucagon, mannitol and IV
glucose with patient at ALL times
59. DKA
Prevention
⢠50% DKA admissions are in known
diabetics
⢠Failure of Physician-Patient relationship
â non-compliance
â Inappropriate intervention
â Sick day rules need to be understood and
followed
â Availability is essential
60. Typical Therapy - Fluids
Improved Management ?
⢠All patients given 20 cc/kg NS bolus over
30-45 minutes
⢠Started on 0.1 units/kg/hour Insulin without
bolus
⢠Fluids - 2.5 x maintenance of 3/4 NS
regardless of degree of dehydration
⢠Glucose used to maintain insulin rate
Pediatrics 108: 735-740; 2001
61. Typical Therapy - Fluids
Improved Management ?
⢠Outcome
â 23 % fewer fluid changes = decreased error risk
â Mean total fluids in first 24 hours lower (5 vs 4
l/m2/day)
â Dec time to resolve acidosis shorter (16 vs 12
hours) ??
â Reduced fluid cost ($1060 to $776)
Pediatrics 108: 735-740; 2001
62. âTypicalâ SettingâŚ..
⢠7 yo boy with 24 hour history of n/v/d.
Diagnosed with IDDM 2 yrs ago. Woke up with
moderate ketones and dstick of 350 mg/dl.
â Is this DKA ?
â What is your responsibility ?
⢠12 yo patient on CSII. Last 4 hours dsticks
increasing from 120 to 450 mg/dl. Now
complaining of headache and nausea. Large
ketones on dip-stick.
63. DKA
⢠Acidosis
â Primary buffer is intracellular protein
â K+ moves out of cells and H+ moves in
â In association with aldosterone (induced from
hypovolemia)
⢠Potentiates K+ wasting
²² Hypokalemia
65. DKA â Cerebral Edema
Other
⢠Insulin associated activation of Na+/H+
pump
â Not commonly found during initial treatment
â As acidosis resolves, H+ diffuses out of brain
cells and Na+ enters (along with H20)
â Rabbit model - drop in glucose secondary to
insulin administration vs. peritoneal dialysis
results in cerebral edema