Transcript Diabetic ketoacidosis

Supervised by : Dr. Rasha Bondok
Assistant professor of anesthesia and intensive care
Presented by : Lamya Elsayed
Resident of anesthesia and intensive care
case scenario :
 23 yrs old female, IDDM for 15 yrs.
 Presents
with disturbed level of consciousness
,confusion, looks very unwell after having a normal
vaginal delivery without anesthesia.
 Vital data: BP 90/60 mmHg, Pulse 132 bpm, RR 32
breath/m with deep breaths (Kussmauls)
 Examinaton: dry mucous membrane, mild epigastric
tenderness, fruity breath odour and no fever.
Case scenario :
 Labs: Hb 14gm/dl, WBC 20,000, Plt 312,000
 S. glucose 400mg/dl.
 Na = 137mEq/L, K = 3.8mEq/L, Cl = 101mEq/L.
 ABG: pH = 7.15, pCo2 = 23 mmHg, Hco3 = 8 mmol/L
& pO2 = 100 mmHg.
 Blood chemistry shows:
BUN 40, creatinine 2 mg/dl.
Urine: Glucose +4, Ketone +3 .
What Does The ABG Tells Us ?
( PH = 7.15, PCO2 = 23, HCO3 = 8 & PO2 = 100)
o
pH = 7.15 therefore acidosis (severe).
o
pCO2 = 23 therefore not resp. acidosis.
o
HCO3 = 8 therefore metabolic acidosis
o
Anion gap = Na + K – (Cl + HCO3 )
=137 + 5 – (101+ 8) = 33 (>14)
-
-
High anion gap metabolic acidosis with respiratory
compensation
Ketonemia /
ketonuria
hyperglycemia
DKA
Metabolic
acidois
Questions :
 Can serum glucose be normal in DKA ?
 What are the cut off values for PH and HCO3 in DKA ?
 Is there any other types of acidosis in DKA ?
Who is at risk of DKA ?
 More common in IDDM esp. in pts on insulin pump. why ?!
 Can still happen in NIDDM. When ?!
 1/5 of cases are 1st time presenters
 Most of cases are precipitated by certain factors : stress of
surgery, infection, trauma or a serious underlying medical
illness e.g. stroke, MI
 No underlying precipitating factors can be detected in small
percentage of cases.
Pathophysiology
of DKA
INSULIN
COUNTERREGULATORY
HORMONES
 DKA is considered an extension of the
physiological state desinged to overcome
starvation. in this case the relative carbohyrate
unavailability caused by lack of insulin mimics
a state of starvation.
 Both lack of insulin and excess glucagon
contribute to the 2 main processes taking
place in DKA : hyperglycemia and ketosis
Mechanism of hyperglycemia
1. Lack of insulin : inhibit glycolysis , stimulate
glycogenolyis and gluconeogenesis.
2. Excess glucagon : inhibit glycolysis. How ?
It inhibits formation of fructose 2,6 biphosphate which
is an extremely potent allosteric regulator of a major
rate limitting enzyme in the pathway of glycolysis
(phosphofructokinae enzyme)
Effects of hyperglycemia :
o Hyperglycemia leads to hyperosmolarity that in turn
cause osmotic diuresis and loss of water and electrolytes
in urine and although hyperosmolarity shifts water to ECF,
hypervolemia doesn’t occur dt concomitant osmotic
diuresis.
o severe dehydration, dehydration is augmented by
vomiting and later DCL decreasing fluid intake.
Mechanism of ketosis :
1. Lack of insulin : stimulates lipolysis that deliver FFA
used for ketogenesis.
2. Excess glucagon : Citric acid (the product of krebs
cycle I.e. glucose metabolism that Is inhibited by
glucagon as decribed before) is responsible for
regulation of activity of acetyl coA carboxylase. The
later synthesize malony coA in the liver which turn off
carnitine acyl transferase 1 that is the rate limitting
enzyme in ketogenesis. ( so turn off the supply of
substrate into krebs cycle and ketogenesis is
automatically turned on ).
Effects of ketosis :
 Metabolic acidosis increasing anion gap
 Draws out intracelluar cations a sodium and potasium
 Vomiting that aggravates dehydration
Total body stores of K are depleted due to urinary loss
however s.K maybe intially elevated due to acidosis
pulling intacellular K out. It markedly decrease with
insulin therapy that stimuate the influx of K into the
cells and with correction of acidosis.
fat cell
DKA: Pathophysiology
Glucose
Insulin
+ PFK
TG
Ketoacids
Insulin
+
HSL
FFA
Liver Cell
Pyruvate
Kreb’s
Cycle
Acetyl-CoA
+
Fatty
Acyl-CoA
Glucagon
Insulin
+
VLDL (TG)
Clinical manifestations of DKA
 Polyuria, Polydipsia, Polyphagia
 Dehydration + orthostasis
 Vomiting (50-80%)
 Abdominal pain present in at least 30%.
 Küssmaul respiration if pH < 7.2
 Temperature usually normal or low, if elevated think
infection!
 Lethargy, delirium
How to manage a case
of DKA ?
Broad lines of treatment :
Rehydration
Insulin therapy
DKA
Electrolyte repletion
Management of
complications and
evaluation of therapy
 Priority is given to correction of the state of
hyperosmolarity and dehdration. rehydration should be
done gradually to prevent overshooting of s.NA levels.
 Insulin therapy is started only after support of
heamodynamics to prevent latent shock of rehydration
 Potassium replacement is started even with normal
levels as it is expected to dramatically drop with insulin
therapy.
 100 % O2 is given to all cases of DKA even if the
saturation is 100 % on RA.
rehydration
Rehydration
Volume! Volume! Volume

Objectives:
 1- Restore intravascular volume.
 2- Reduce blood glucose level.
 3- Reduce counter regulatory hormones.
(catecholamines, glucagon)
Augment insulin sensitivity.
How much fluid will you give ?
 15 – 20 ml/kg . (1-2 L ) in 1st hour
 500 ml/h for next 2 hours or 1L /h if in shock
 500-250 ml/h according to hydration status ( UOP & renal
functions).
 maintainence fluids should be provided.
How much fluid will you give ?
 Subsequent choice for IV fluids depends on:
1-Corrected serum Na (Nac)
2- Effective serum osmolarity (E osm)
o If E osm > 320 mOsm/L or Nac is normal/elevated
 0.45% NaCl 4-14 ml/Kg/hr
o If E osm <320 mOsm/L or Nac is low
 0.9% NaCl at a similar rate of 4-14 ml/Kg/hr.
 S.NA is a good marker for hyperosmolarity and
intracellular dehydration but it might be inaccurate in
case of DKA as hyperosmolarity is predominantely caused
by hyperglycemia so scaling s.NA in relation to s.glucose
(corrected s.NA) is a better judge of free water deficit.
 Osmolarity is a the conc. Of an osmolar fluid while
effective osmolarity (tonicity) is the osmolar pressure of
this solution. it calculates only the effective molecules
able to draw water across cell membrane (mannitol ,
glucose) and excludes freely diffusible substances (urea)
that produce no effect on tonicity .
 Corrected serum Na + (Nac) =


measured Na + [1.6×serum glucose mg/dl -100]
100
Serum osmolarity mOsm/L =
2×Na (mEq/L) + s.glucose(mg/dl) + BUN(mg/dl)
18
2.8
E osm (mOsm/L) =
2×Na (mEq/L) + s.glucose (mg/dl)
18
Successful progress is judged by :
 Haemodynamic monitoring (pulse-BP)
 Adequate urine output.
 Improved mental status.
 Monitoring the decrease in E osm. ( should not exceed
3 mOsm/L/hr )
caution Gradual rehydration over 36 - 48 hours. why ?
1.avoid iatrogenic fluid overload and cerebral oedema (how)
2.overly aggressive fluid replacement leads to overshooting of
NA levels leading to further increase in plasma osmolarity increasing
risk of pontine myelinolysis.
Insulin
therapy
 insulin therapy aims at controlling hyperglycemia and
reversing lipolysiss.
It should be delayed at least 1 hr after fluid therapy to
prevent latent shock of rehydration and it can be
delayed further more if serum levels of K is below
normal.
There is no evidence that that the IV route is better
than the SC route except in cases of shock.
How to supply insulin ?
 A Loading dose 0.1U/Kg IV bolus
 Then maintainence rate of infusion U/hr =
s.glucose mg/dl
150 or 100 if Steroids
Infection
Overweight
Infusion rate is doubled for an hr if insulin resistense is suspected
and s.glucose is rechecked in an hr.
• Once s. glucose falls to 250 mg/dl, add DW5% at a rate of 50 ml/hr to
maintain stable glucose level (i.e to allow continuation of insulin infusion
till reversal of lipolysis without episodes of therapy induced hypoglycemia).
 Maximum rate of glucose decline/ hr is
75-100 mg/dl regardless the dose of insulin.
 Failure of s.glucose level to fall by 75-100 mg/dl/hr implies
inadequate volume administration or impaired renal function
rather than insulin resistance.
 serum HCO3 < 20 mEq/L even with normal glucose level
implies continued need for glucose-insulin inf. till reversal of
lipolysis (decreased s.HCO3 is an indicator of persistent ketosis
as HCO3 regeneration automatically occurs when insulin
sensitivity is restored . This occurs via renal and hepatic
mechanisms. hepatic mechanism uses ketones as a
substarate).
How to stop Insulin infusion ?
 Sliding scale has to be started at least 2 hrs prior to
discontinuation of insulin infusion .
 Total daily intake : total req. of insulin in insulin infusion
per day / total insulin dose calculated by sliding scale per
day . Either dose is divided into 1/3 and 2/3 and given by
the usual SC regimen.
Electrolyte
replacement
 Total K stores are depleted due to renal loss (osmotic
diuresis) even if serum levels are high or normal
(shift of K outside the cell due to hyperosmolarity).
insulin therapy causes shift of K inside cells so s.K
falls further more reaching its peak in 2-4 hrs (1
meq/L / 0.1 unit ) .
 20-40 meq /L are given if s.K is equal to or less than
5.5 meq/L. max. rate of infusion is 0.5 meq/kg/hr.
should bicarbonate be given ?
 The use of NAHCO3 in DKA remains controversial.
 There is no doubt that PH is markedly improved but at the
expense of worsening intracellular acidosis and other side
effects that overshadow any potenial benefits such as CO2
production, rebound alkalosiss, hypovolemia and volume
overload. Also in the context of DKA ,it might delay clearence
of ketones and may further enhance hepatic production.
 In PH less than 6.9, most authors recommend use of
bicarbonate to partially correct acidosis, the threshold of
NAHCO3 use is debatable between 6.9 and 7.1
Management of complications and evaluation of
therapy
cerebral oedema
 It maybe subclinical at the beginning of therapy and the CSF
pressure is normal.
 Classically, labs are improving and there is no way to predict
who is going to have this complication. it occur typically in the
1t 24 hrs of therapy with no way to see it coming.
o Mechanism :
Brain conserves water by producing osmoprotective
molecules (taurine). Osmolarity becomes disproportionately
higher in the brain than other tissues. Sudden fall in serum
osmolarity during rapid rehydration moves fluid across the
blood-brain barrier. Brain becomes relatively hypervolemic. So
Cerebral edema is a complication of therapy, not a progression
of DKA.
Pathophysiology of cerebral oedema
EC glucose rises causing loss of
water from IC space which is lost
in osmotic diuresis
Later the brain generates
idiogenic osmoles which serve
to draw water back into the
cerebrum
Presentation of cerebral oedema
• Initial complaint of headache,Progresses to decreasing
level of consciousness, hypertension, papilledema,
blurring of vision and bradycardia. Coma and death soon
follow
• Diagnosis is available with CT scan.
• The best therapy is to prevent it with careful rehydration
 Therapy for acute episode:
 Intubation and hyperventilation
 IV Mannitol 0.5 - 1.0 Gram/Kg ( bolus) .
 IV sedation.
 Slow the rate of osmolar correction.
Management of cerebral oedema
 The best therapy is to prevent it with careful rehydration.
 Diagnosis is available with CT scan.
 Therapy for acute episode:
 Intubation and hyperventilation
 IV Mannitol 0.5 - 1.0 Gram/Kg as bolus.
 IV sedation.
 Slow the rate of osmolar correction.
Evaluation of therapy
 Controlled reduction in serum glucose.
 Correction of acidosis “closing the gap”.
 Clearing of serum ketones.
 Clinical improvement :
 fall in respiratory rate
 improved perfusion
 improving mental status.