The Journal of International Medical Research
2011; 39: 143 – 149
The Effects of Colloid Pre-loading on
Thromboelastography Prior to Caesarean
Delivery: Hydroxyethyl Starch 130/0.4
versus Succinylated Gelatine
G TURKER, T YILMAZLAR, E BASAGAN MOGOL, A GURBET, S DIZMAN AND H GUNAY
Department of Anaesthesiology, Uludag University Medical Faculty, Bursa, Turkey
This prospective, randomized, double- and after pre-loading. Both groups had
blind study compared the effects on significantly shorter r-time and lower
thromboelastography (TEG) of pre- MA after pre-loading. The a-angle was
loading with two different colloid fluids significantly decreased after pre-loading
prior to spinal anaesthesia for caesarean with HES but not with GEL. No
section. Healthy full-term parturients significant differences in k-time were
received either 500 ml 6% hydroxyethyl induced pre-loading. In conclusion, pre-
starch 130/0.4 (HES, n = 25) or 500 ml 4% loading with HES or GEL was associated
succinylated gelatine (GEL, n = 25) prior with a mild hypocoagulable effect in
to spinal anaesthesia. TEG parameters healthy parturients presenting for
including reaction time (r-time), clot elective caesarean section; however, all
formation time (k-time), clot formation TEG parameters in both groups
rate (a-angle) and maximum amplitude remained within or very close to the
(MA) were measured immediately before normal range after pre-loading. 
KEY WORDS: COLLOID PRE-LOADING; THROMBOELASTOGRAPHY; CAESAREAN SECTION; 
SPINAL ANAESTHESIA
Introduction this procedure may affect direct or indirect
Neuraxial anaesthesia is a popular choice coagulation pathways.8,9
for obstetric surgery. Side-effects of neuraxial Screening tests allow interpretation of
anaesthesia include hypotension and several phases of the coagulation cascade.
bradycardia,1,2 which may result in nausea, Thromboelastography (TEG) is a real-time
vomiting and, more importantly, fetal monitor of whole-blood coagulation that
acidosis due to reduced uteroplacental blood measures the viscoelastic properties of blood,
flow.3 – 5 Fluid pre-loading is advocated to as well as coagulation factors and platelet
reduce the incidence and severity of activity, from a single blood sample. TEG is
hypotension following neuroaxial more reliable and provides more
anaesthesia, with colloids considered to be comprehensive information than other
more effective than crystalloids;6,7 however, coagulation tests.10 – 12
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Colloid pre-loading prior to spinal anaesthesia
Although pregnancy is associated with Haematological tests (haemoglobin level,
hypercoagulability, little is known about the platelet count, prothrombin time,
effects of fluid pre-loading on coagulation in international normalized ratio and activated
pregnant patients. The aim of the present prothrombin time) were performed for all
study was to evaluate the effect on patients prior to fluid pre-loading. Subjects
coagulation of fluid pre-loading with either were not pre-medicated. All subjects were
6% hydroxyethyl starch (HES) or 4% monitored using non-invasive blood pressure
succinylated gelatine (GEL), prior to spinal monitoring, pulse oximetry and
anaesthesia. electrocardiography. An 18-gauge
intravenous cannula was inserted into a
Subjects and methods forearm vein. The initial 3 ml of blood was
SUBJECTS AND INCLUSION discarded to avoid tissue contamination, and
CRITERIA a further 1-ml blood sample was obtained for
In this prospective, randomized, double- analysis of baseline TEG values. Fluid pre-
blind trial, pregnant women at term (37 – 41 loading was performed over 20 min through a
weeks’ gestation) who were American Society 20-gauge intravenous cannula inserted into a
of Anesthesiologists physical status I – II (i.e. hand vein. A second blood sample was then
normal healthy patients or patients with obtained from the forearm cannula, using the
mild systemic disease) and were scheduled to sampling technique previously described. 
undergo elective caesarean section at the The TEG analysis was performed by
Uludag University Teaching Hospital, Bursa, another anaesthesiologist (T.Y.) who was
Turkey, between May 2008 and January blinded to patient randomization. Within 3
2010, were enrolled sequentially into the min of blood sampling, 1 ml of whole blood
study. Women with significant comorbidities was placed into a vial containing 1% kaolin.
(including liver disease, hypertension, After mixing by inversion seven to 10 times,
diabetes mellitus, pre-eclampsia or pre- 360 µl of kaolin-activated blood was put into
existing coagulation disorders) were a plastic cup in a pre-warmed TEG analyser
excluded, as were those receiving aspirin or (37 °C). Standard TEG parameters were
anticoagulant therapy. recorded using a Thrombelastograph® 5000
The study protocol was approved by the analyser (Haemoscope Corp., Niles, IL, USA).
Ethics Committee of Uludag University, The reaction time (r-time) was defined as the
Bursa, Turkey and written informed consent time from the start of recording until initial
was obtained from all participants. fibrin formation and represented the
function of clotting factors. The k-time was
STUDY TREATMENT AND TEG defined as the time from r-time until a fixed
ANALYSIS level of clot firmness and reflected the
Randomization was carried out using a dynamics of clot formation. The α-angle was
computer-generated schedule. Each subject defined as the slope of the TEG trace from r
was assigned to receive pre-loading with 500 to k and represented the rate of fibrin build-
ml of either 6% HES 130/0.4 (Voluven®; up and cross-linking. The maximum
Fresenius, Bad Homburg, Germany) (HES amplitude (MA) reflected the ultimate
group), or 4% GEL (Gelofusine®; B. Braun strength of the fibrin clot. 
Melsungen AG, Melsungen, Germany) (GEL After the second blood sample was
group). obtained, spinal anaesthesia was performed
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Colloid pre-loading prior to spinal anaesthesia
with the patient in the left lateral decubitus for each group were assessed using
position, and a 27-gauge Quincke needle Wilcoxon’s signed-rank test. The
(Spinocan®; B. Braun Melsungen AG) was independent t-test or Mann–Whitney U-test
inserted at the L3 – L4 or L4 – L5 was used, where appropriate, for intergroup
intervertebral space. A mixture containing 8 comparisons of changes in TEG variables.
mg hyperbaric bupivacaine and 20 µg Nominal non-parametric data were
fentanyl (2 ml total volume) was injected analysed using Fisher’s exact test. A P-value
into the subarachnoid space. The patient < 0.05 was considered to be statistically
was then shifted to the supine position for significant. 
the remainder of the procedure. All spinal
needles were inserted by the same Results
anaesthesiologist (G.T.) who was blinded to Fifty pregnant women at full-term were
the patient randomization. Sensory blockade recruited into the study: 25 were randomized
was evaluated using the pinprick test with a to each of the HES or GEL groups, and all
hypodermic 20-gauge needle, and subjects were included in the analyses. The
dermatomal levels were tested every 60 s on two groups were comparable with respect to
the midline until the level stabilized (defined age, weight, height, gestational age,
as the same result in four consecutive tests). haemoglobin levels, platelet counts and
Heart rate (HR), systolic and diastolic arterial coagulation tests (Table 1). No subject had
blood pressures (SAP and DAP, respectively) any pre-operative coagulation abnormalities
and peripheral oxygen saturation (SpO2) or thrombocytopoenia. 
were measured and recorded at 5-min There were no significant differences
intervals, intraoperatively. Bradycardia (HR between the groups with respect to
< 50 beats/min) or intraoperative hypotension intraoperative findings for HR, SAP, DAP or
(SAP < 20% of baseline) were recorded and SpO2 (data not shown). Analysis showed no
treated with fluid bolus or intravenous significant differences between the two
ephedrine or atropine. Apgar scores for groups with regard to the highest level of
newborns were recorded at 1 and 5 min after sensory block, total crystalloid volume
delivery. The Apgar score comprises 5 infused, number of subjects who developed
components, each of which is given a score hypotension, total ephedrine dose used and
of 0, 1, or 2: HR; respiratory effort; muscle neonatal Apgar scores (Table 2). No subject
tone; reflex irritability; and colour. developed bradycardia during surgery.
There were significant decreases in r-time in
STATISTICAL ANALYSES both groups after pre-loading (P < 0.001 for
Data are presented as mean ± SD or median both groups; Table 3). There was a significant
(range). Statistical analyses were performed decrease in α-angle with HES, but not GEL 
using the SPSS® statistical package, version (P < 0.05; Table 3). MA was significantly
13.0 (SPPS Inc., Chicago, IL, USA) for decreased after pre-loading in both groups 
Windows®. A group size of 25 was calculated, (P < 0.01), but no differences in k-time were
based on 90% power, to be able to detect a observed (Table 3). The changes in TEG
30% difference in r-time between study parameters after colloid pre-loading, although
groups. Demographic and intraoperative significant, remained within the normal range
data were analysed using Student’s t-test. or just below the lower limit of the normal
TEG parameters before and after pre-loading range (for r-time) in both groups,13 and there
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Colloid pre-loading prior to spinal anaesthesia
TABLE 1:
Demographic characteristics and pre-operative haematological results for parturients
receiving either 6% hydroxyethyl starch 130/0.4 (HES) or 4% succinylated gelatine (GEL)
before spinal anaesthesia for caesarean section
HES (n = 25) GEL (n = 25)
Age, years 29 ± 4 29 ± 4
Weight, kg 71 ± 13 74 ± 13
Height, cm 162 ± 4 161 ± 5
Gestational age, weeks 38 ± 0.9 38 ± 0.9
Pre-operative haematological tests
Haemoglobin, g/dl 11.9 ± 1.7 11.7 ± 1.4
Platelet count, × 103/mm3 282 ± 77 266 ± 70
Prothrombin time, s 12.9 ± 1.4 12.7 ± 1.6
Activated prothrombin time, s 25.2 ± 3.0 24.6 ± 4.0
International normalized ratio 1.2 ± 0.4 1.1 ± 0.3
Data presented as mean ± SD.
No statistically significant between-group differences (P > 0.05); Student’s t-test.
TABLE 2:
Intraoperative outcomes for parturients receiving either 6% hydroxyethyl starch 130/0.4
(HES) or 4% succinylated gelatine (GEL) before spinal anaesthesia for caesarean section
HES (n = 25) GEL (n = 25)
Highest level of sensory block, thoracic 5 (4 – 6) 5 (3 – 6)
Total crystalloid fluid infused, ml 1188 ± 286 1260 ± 233
Patients with hypotension 2 4
Total ephedrine used, mg 2.5 ± 4.2 4.4 ± 6.8
Newborn Apgar score
1 min 8.1 ± 2.0 8.4 ± 1.1
5 min 9.6 ± 0.8 9.4 ± 0.7
Data presented as mean ± SD, median (range) or n of patients.
No statistically significant between-group differences (P > 0.05); Student’s t-test.
were no intergroup differences in any in any subject. Median r-time values were
parameter at any time (Table 3). just below the lower limit of the normal
reference range after pre-loading. It
Discussion appeared that the two colloids had similar
The present randomized, double-blind, in slight effects on coagulation.
vivo study demonstrated that both 6% HES Physiological alterations during
and 4% GEL caused a significant reduction pregnancy result in increased platelet
in r-time and MA in healthy pregnant aggregation, fibrinogen concentration and
women undergoing caesarean delivery coagulation factors, decreased endogenous
under spinal anaesthesia; however, MA anticoagulants (proteins C and S) and
remained within the normal reference modified fibrinolytic capacity,14 resulting in
range.13 No clinical signs of abnormal a hypercoagulable state. This is consistent
coagulation were observed after pre-loading with the present study, where baseline MA
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Colloid pre-loading prior to spinal anaesthesia
TABLE 3:
Thromboelastographic data before and after colloid pre-loading in parturients receiving
either 6% hydroxyethyl starch 130/0.4 (HES) or 4% succinylated gelatine (GEL) before
spinal anaesthesia for caesarean section
HES GEL
Thrombo- (n = 25) (n = 25)
elastographic
measure Before pre-load After pre-load Before pre-load After pre-load
r-time, min 6.3 (2.2 – 11.8) 3.8 (1.5 – 9.9)*** 6.0 (2.3 – 10.6) 3.7 (1.9 – 9.2)***
k-time, min 1.8 (1.0 – 3.8) 1.9 (1.2 – 3.5) 1.8 (1.3 – 4.6) 1.9 (1.3 – 2.8)
α-angle, ° 65.2 (34.9 – 76.4) 61.1 (44.1 – 72.5)* 60.9 (41.7 – 73.3) 59.9 (47.8 – 71.5)
MA, mm 76.1 (55.6 – 91.9) 70.5 (53.5 – 83.6)** 76.8 (56 – 82.7) 70.2 (58.4 – 81.9)**
Data presented as median (range).
*P < 0.05, ** P < 0.01, *** P < 0.001 versus before pre-load measurements (Wilcoxon’s signed-rank test).
r-time, reaction time (normal range 4 – 8 min); k-time, clot formation time (normal range 1 – 4 min); α-
angle, clot formation rate (normal range 47° – 74°); MA, maximum amplitude (normal range 55 – 73 mm).
values were above the upper limit of the Gelatine solutions may have fewer
normal reference range in both the HES and negative effects on coagulation than
GEL groups. HES,19,22,23 although not all studies agree.8,24
Fluid pre-loading to reduce hypotension These studies were conducted under in vivo or
during spinal anaesthesia for caesarean in vitro conditions in non-obstetric
delivery is now routine, and colloids may be populations, and different preparations from
more effective than crystalloids.15,16 There is, those used in the present study were
however, little data on the changes in administered. Butwick and Carvalho13
coagulation following colloid treatment in compared TEG changes after pre-loading
pregnant women. Previous TEG studies have with 500 ml 6% HES and 1500 ml lactated
shown that haemodilution of > 20% with Ringer’s prior to caesarean delivery. They
HES affects coagulation in non-obstetric found that r-time and k-time were
patients,17 – 19 and that mild-to-moderate significantly prolonged in the HES group, but
HES haemodilution decreases circulating MA values were similar, and no significant
factor VIII and von Willebrand factor, differences in TEG values were seen in the
inhibiting platelet function.20 Low molecular group that received lactated Ringer’s. Pre-
weight HES, with a low degree of molar loading with 500 ml HES was associated with
substitution, has less effect on haemostasis a mild hypocoagulable effect in healthy
than equivalent high molecular weight HES parturients undergoing caesarean delivery,
with higher molar substitution.17,21 The but TEG parameters after HES pre-loading
differences between the individual remained within a normal reference range.13
pharmacokinetic features of HES Based on the above, a control group was not
preparations may therefore be important; in included in the present study, as it was
the present study, a low molecular weight assumed that crystalloid solutions would
HES with lower molar substitution (500 ml have no significant effect on any TEG
6% HES 130/0.4) was used, which may have parameters. The lack of a control group
had less of an impact on haemostasis limits the usefulness of the present study. The
compared with other HES preparations. finding that r-time and MA were decreased
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Colloid pre-loading prior to spinal anaesthesia
after pre-loading with either HES or GEL did moderate haemodilution and pregnancy-
not agree with that of Butwick et al.,13 associated hypercoagulation.
although both studies found only minimal In conclusion, pregnant parturients who
alterations in TEG parameters. received fluid pre-loading with 500 ml of 6%
Ruttmann et al.25 reported that mild and HES 130/0.4 or 4% GEL did not experience
moderate haemodilution increased the arterial hypotension induced by spinal
coagulability of whole blood in vitro, but that anaesthesia prior to undergoing elective
saline haemodilution had a more marked caesarean sections. Both colloid fluids
effect on final clot strength than a modified produced a mild hypocoagulable state, but
gelatin colloidal solution (Haemaccel®). It is TEG parameters after pre-loading remained
possible that this hypercoagulable state is within or just below a normal reference
normally seen in the perioperative period, as range. Further studies are necessary to assess
a result of the acute-phase response to the effects of other fluid pre-loading
surgery.13 In vivo coagulation studies are regimens on coagulation and clinical
necessary to assess potential associations outcomes in pregnant women.
between perioperative fluid regimens and
clinical outcomes. The decrease in r-times Conflicts of interest
observed in both the HES and GEL groups in The authors had no conflicts of interest to
the present study may be due to this mild-to- declare in relation to this article. 
• Received for publication 14 September 2010 • Accepted subject to revision 6 October 2010 
• Revised accepted 7 December 2010
Copyright © 2011 Field House Publishing LLP
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Author’s address for correspondence
Associate Professor Gurkan Turker
Department of Anaesthesiology, Uludag University Medical Faculty, 16059 Bursa, Turkey.
E-mail: ygturker@gmail.com
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