Critical Care March 2009 Vol 13 Suppl 1 29th International Symposium on Intensive Care and Emergency Medicine
be detected in healthy and anticoagulated blood. We compared
the gel time (GT) required to form the incipient clot and the
corresponding fractal dimension (df) against laboratory markers of
haemostasis and thromboelastography (TEG).
Methods Blood samples were taken from 52 healthy adults and
similarly 34 individuals whose blood had been anticoagulated with
heparin over the therapeutic range.
Results The incipient clot in normal blood is established as a
sample-spanning network cluster at the GP . The value of df in
whole healthy human blood is 1.74 (0.07), which indicates a high
degree of branching in the fibrin network at criticality and is
commensurate with that reported to arise in other biological
systems. There was a significant reduction in the value of df and a
corresponding prolongation in the GT in the heparin group as
compared with the healthy group (Figure 1).
Conclusions We describe for the first time that the incipient clot
formed at the GP of whole blood is characterized by a fractal
microstructure. The values of df and GT discriminate between clot
structure in healthy and anticoagulated blood. The relationship
between these new markers may provide a basis for exploring the
relationship between coagulation pathways and clot quality.
1. Evans PA, et al.: Rheometrical detection of incipient blood
clot formation by Fourier transform mechanical spec-
troscopy. J Non Newt Fluid Mech 2008, 148:122-126.
2. Muthukumar M, Winter HH: Fractal dimension of a cross-
linking polymer at the gel point. Macromolecules 1986, 19:
Acquired bleeding model induced by dilutional
coagulopathy in the rabbit
I Pragst, B Doerr, F Kaspereit, W Krege, E Raquet, G Dickneite
CSL Behring GmbH, Marburg, Germany
Critical Care 2009, 13(Suppl 1 ):P437 (doi: 10.1186/cc7601)
Introduction Severe traumatic or intraoperative blood loss
necessitates massive transfusion. This blood loss and the dilution
of coagulation factors result in insufficient haemostasis. Treatments
to enhance the haemostatic capacity need to be evaluated. An
acquired bleeding model due to a dilutional coagulopathy was
developed in the rabbit to estimate the contribution of PCC
(Beriplex P/N; CSL Behring) on haemorrhage.
Methods Rabbits were anesthetised using isofluran and were
mandatorily ventilated. The animals were instrumented to monitor
the cardiovascular and respiratory system. Dilutional coagulopathy
was induced by phased blood withdraw, salvaged erythrocyte
retransfusion and volume substitution with hydroxyethyl starch.
After the dilutional procedure the bleeding was inflicted by cutting
the lateral kidney pole. To characterise the model, animals were
allocated to groups: I, sham operation (no dilution, placebo
treatment; n = 5); II, negative control (dilution, placebo treatment;
n= 7); III, PCC 25 U/kg intravenously (dilution, verum treatment;
n=6). Coagulation factor activity, thrombin generation (TGA),
prothrombin time (PT) and the bleeding from the kidney wound
Results Rabbits without a dilutional coagulopathy demonstrated
rapid onset of haemostasis. Post-injury blood loss (BL) and time to
haemostasis (TH) were 4.7 2.4 ml and 4.4 1.1 minutes,
respectively. After the dilution procedure coagulation factors were
reduced to less than 50% of baseline. Haemostasis deteriorated
S176 after colloid transfusion (BL 60.0 25.9 ml, TH 19.1 2.2 min).
The TGA showed normal lag phase but only 50% of the normal
peak thrombin level. The PT was prolonged after the dilution about
1.8-fold. Using PCC treatment it was demonstrated that the peak
thrombin level was corrected (P <0.0001) and the BL (21.5
11.1 ml; P<0.01) as well as TH (12.4 1.4 min; P<0.01) were
Conclusions In this rabbit model of a dilutional coagulopathy it
was demonstrated that a dilution of coagulation factors of more
than 50% affects TGA, PT and bleeding. Restoration of
coagulation factors II, VII, IX and X using PCC corrects the TGA
and reduces BL and TH. This model could be used to investigate
new drugs in dilutional coagulopathy.
Impact of nebulized unfractionated heparin and
N-acetylcysteine in management of smoke inhalation
E Elamin1, A Miller2
1University of Florida, Gainesville, FL, USA; 2State University of
New York Downstate & Kings County Hospital, Brooklyn, NY, USA
Critical Care 2009, 13(Suppl 1):P438 (doi: 10.1186/cc7602)
Introduction Approximately 70% of all fire victims in the USA who
die within the first 12 hours post burn die from smoke inhalation
injury (SIJ). Airway edema combined with obstructive casts
produced from cellular debris, fibrin clots, polymorphonuclear
leukocytes, mucus and mucin B5 are believed to cause the airway
obstruction contributing to pulmonary failure.
Methods A single-center retrospective study with historical control
over a 5-year period of 30 mechanically ventilated adult subjects
admitted within 48 hours of their bronchoscopy with confirmed SIJ.
Both the experimental (n = 16) group and control (n = 14) groups
were treated with ventilator support but the former received in
addition 10,000 units of nebulized heparin sulfate mixed in 3 ml
normal saline every 4 hours and 3 ml 20% nebulized N-
acetylcysteine plus 0.5 ml albuterol sulfate every 4 hours for 7
consecutive days starting on the day of admission. We calculated
APACHE III scores on admission in addition to the daily lung injury
score for 7 days.
Results There was no significant difference in admission APACHE
III scores (38.7 vs. 34.6; a = 0.05) or lung injury scores (0.7 vs.
1.1; a = 0.05) between the experimental and control groups. The
experimental group showed significant improvement in lung injury
scores (P <0.05) over the duration of the study, with the greatest
benefit seen over the first 7 days (0.91 0.14 vs. 1.79 0.41;
P<0.01). Respiratory resistance and compliance measurements
revealed significant improvement in the experimental group
reaching a significance level of P <0.01 by day 4. There was a
statistically significant survival benefit in the experimental group
that was most pronounced in patients with APACHE III scores
>35. Survival for the control group versus experimental group was
0.5714 0.1497 versus 0.9375 0.0605, respectively (RR =
-0.0055; 95% Cl = -0.0314 to 0.0204; HR = 1.003).
Conclusions The use of aerosolized unfractionated heparin and N-
acetylcysteine attenuates lung injury and the progression of acute
lung injury in ventilated adult patients with SIJ.
1. Desai MH, Mlcak R, Richardson J, et al.: J Burn Care Rehabil
2. Tasaki 0, Mozingo DW, Dubick MA, et al.: Crit Care Med