Endocrinology Dr.Naji kadhim shlaibah al-darajie

3. Most patients treated in this manner recover
uneventfully, with resolution of diabetic
ketoacidosis; however, in a small percentage of
patients (approximately 0.5 to 1%), signs of
elevated intracranial pressure and frank
encephalopathies,
.
Even after rapid intervention with intravenous mannitol
or hypertonic 3% saline, the prognosis remains
guarded, with death resulting in some cases and
persistent disabilities in others.

4. The term cerebral edema is used to describe this
complication, which is more likely to occur in
patients who have greater severity of acidosis,
a lower partial pressure of carbon dioxide
(PCO2), and a higher blood urea nitrogen level
and in younger children.

5. Some studies suggested that rapid infusion of more than 4
liters per square meter of body-surface area per day and
the use of hypotonic fluids were more likely to precipitate
cerebral edema,6,7 thereby implicating osmotic
mechanisms, to which medical management may have
contributed.
Residual neurologic deficits, including deficits in memory or
neurologic functions after recovery, were also noted,
which suggested that classic cerebral edema was only
the “ .

6. An alternate hypothesis, based on diffusion-
weighted magnetic resonance imaging,
suggested that the mechanism for cerebral
edema was extracellular edema caused by
vascular endothelial leakage — a
phenomenon characterized by hypoxia or
ischemia, followed by reperfusion injury, rather
than osmosis.

7. To test these hypotheses, and to promote
informed care by physicians, Kuppermann et al.
conducted a controlled trial involving children
with diabetic ketoacidosis that compared the
use of fluid with high sodium chloride content
(0.9%) with the use of fluid with low sodium
chloride content (0.45%), each infused at a
slower or faster rate.

8. The primary outcome was a decline in mental status as
evidenced by two Glasgow Coma Scale scores of less
than 14 (on a scale ranging from 3 to 15, with lower
scores indicating worse mental status) during treatment
for diabetic ketoacidosis.
Secondary outcomes included clinically apparent brain
injury (defined as a deterioration in neurologic status
leading to intervention or resulting in death), short-term
memory impairment during treatment for diabetic
ketoacidosis, and memory and IQ 2 - 6 months after
recovery from diabetic ketoacidosis.

9. The Glasgow Coma Scale score declined to below 14 in 48
episodes (3.5% of the 1389 total number of episodes), and
clinically apparent brain injury occurred in 12 episodes (0.9%);
one patient died.
No significant differences among the treatment groups were
observed with respect to the percentage of episodes in which
the Glasgow Coma Scale score declined to below 14, the
magnitude of decline in the Glasgow Coma Scale score, or the
duration of time in which the Glasgow Coma Scale score was
less than 14; with respect to the results of the tests of short-
term memory; or with respect to the incidence of clinically
apparent brain injury during treatment for diabetic ketoacidosis.

10. The time to resolution of diabetic ketoacidosis and the duration of
hospitalization were also similar among the groups.
****Neither the rate of infusion nor the sodium chloride content of
intravenous therapy at the concentrations and times specified, which
are currently used in clinical practice, significantly influenced
neurologic outcomes of diabetic ketoacidosis in the children in this
trial.
Thus, in the current study, which was performed at specialized centers
with specialized staff, diabetic ketoacidosis–related brain injury
appears unlikely to have been caused by the composition or rate of
intravenous fluid therapy; other mechanisms need to be explored.

11. These conclusions are likely to generate discussion
and lead to revision of current recommendations.
Some results in the current trial hint at better
outcomes with the faster rate of infusion.
The fact that clinical impairment of brain function
occurred predominantly in patients who had more
severe acidosis and a lower PCO2 level suggests
that such patients require more careful monitoring.

12. The one death and the absence of residual
neurologic deficits among those who survived
are consistent with findings in another
report5 and at test to the need to refer children
with diabetic ketoacidosis to specialized centers;
earlier studies had reported death or disability in
30 to 50% of episodes of cerebral edema.

13. Better understanding of the blood–brain barrier
and its alterations in diabetic ketoacidosis may
provide new targets for therapy in patients with
cerebral edema, and campaigns to educate and
heighten awareness of diabetes in the medical
and communities should reduce the incidence
of diabetic ketoacidosis at initial diagnosis.