Discussion:
The incidence of DKA amongst all pediatric age groups is rising, but
especially in children less than five years of age [5]. In fact, DKA
as the presentation of DM is much more common in children less than five
years of age than any other age group, with up to 36% presenting with
ketoacidosis [20, 21]. DKA management may necessitate CVC placement
when obtaining peripheral access is difficult and infusion of medication
and fluids is needed emergently. DKA is often associated with severe
dehydration making it difficult to obtain IV access quickly, especially
in children [22]. Adipose tissue distribution, smaller veins, and
dehydration only enhances the difficulty [23].
Data from this study confirmed that children with DKA utilizing CVCs for
disease management are at high risk for VTE development
(~50% prevalence), and that children with DKA
undergoing CVC placement are at a greater risk for developing
CVC-associated VTE than those of a similar age group with CVC placed for
any other reason. Our data also showed that children with DKA undergoing
CVC placement are younger than those that do not (median age of 17
months vs. 33 months). Yet, assessment of both laboratory and
demographic data amongst this patient population did not reveal any
predictive indicators for VTE. In fact, the only significant difference
between those with VTE and without VTE was length of hospital stay. This
difference could be attributed to the acuity of the patients with VTE
development. However, length of CVC use and degree of acidosis at
presentation in the two patient groups was similar. A possible reason
for the longer hospital stay was for VTE education and management.
At our institution from January 2002 through April 2007, there were 13
CVC placements for DKA management out of the 60 admitted patients.
Specifically between February 2007 and April 2007, five of the seven
patients admitted with DKA underwent CVC placement and three of these
patients developed VTE. Only four of the 82 patients admitted for DKA
underwent CVC placement after April 2007 and none had CVC-associated
VTE. The decrease in CVC placement and CVC-associated VTE in this
patient group is likely multifactorial. One patient had initial fluid
resuscitation via an intraosseous tibial access at a referring hospital
and had an external jugular CVC placed on arrival at our institution for
continuing management. This patient’s VTE risk may have been lessened by
fluid resuscitation prior to CVC placement. Also, fewer CVC were placed
for acute DKA management likely due to recent institutional experiences
and increased awareness of the VTE risk in children with DKA undergoing
CVC placement [15, 18, 19]. Two of the five patients that presented
after April 2007 received continuous unfractionated heparin for VTE
prophylaxis. Given the lack of identifiable predictive VTE indicators
and very high risk (>50% in our population),
anticoagulation prophylaxis should be strongly considered for all young
children with DKA undergoing CVC placement.
The pathophysiology leading to a prothrombotic state in patients with
DKA is not clearly understood. Possible mechanisms include that DKA is
an acute worsening of a chronic hyperglycemic state. Both acute and
chronic hyperglycemia are pro-inflammatory states, which has a known
association with a prothrombotic state [24]. Studies have shown that
critically ill non-diabetic children with hyperglycemia are at higher
risk for VTE development than critically ill children without
hyperglycemia [25]. DKA has also been associated with increased
cortisol levels and growth hormone levels [24]. Unprovoked VTE have
been described in patients with hypercortisolism or elevated growth
hormone levels, suggesting an associated prothrombotic state [26].
Plasminogen has also been shown to be glycated in diabetes leading to
decreased plasmin generation, impaired protein activity, and,
subsequently, hypofibrinolysis [27]. More dedicated research is
necessary to fully understand the mechanisms involved in the
prothrombotic state associated with DM and DKA.
Using a retrospective chart review for data collection does have
limitations. Thrombophilia testing was performed at the discretion of
each provider, and thus was not always performed. Radiographic
investigation for CVC-associated VTE was limited to patients that had
VTE symptoms. Nevertheless, these limitations apply to both the DKA
group and the control groups. Determining length of CVC placement was
difficult in the non-DKA group using a retrospective chart review. We
focused on VTE development within three months of CVC placement in an
effort to capture any CVC-associated thrombus.