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).

pCO2 = 23 therefore not resp. acidosis.

HCO3 = 8 therefore metabolic acidosis

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

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

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 doesnt 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

TG

DKA: Pathophysiology
Glucose
Insulin

+ PFK

Ketoacids

Insulin

HSL
FFA

Liver Cell

Pyruvate

Krebs
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%.
Kssmaul 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 :

 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

Corrected serum Na + (Nac) =

measured Na + [1.6serum glucose
mg/dl -100]
100

Serum osmolarity mOsm/L =

2Na (mEq/L) + s.glucose(mg/dl) +
BUN(mg/dl)
18
2.8

E osm (mOsm/L) =
2Na (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

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

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.

Thank you