Read before you short BTIM -
Here's the posters of the Hextend study presented at the Puerto Rico conference:
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Intraoperative Administration of Hextend Versus 6% Hetastarch in
Saline for the Treatment of Hypovolemia During Major Surgery:
Results of a Randomized Blinded Clinical Trial
E Bennett-Guerrero, MD*; TJ Gan, MD#; DM Moskowith, MD*;
Barabra Phillips-Bute, PhD#; JV Booth, MD#; S Konstadt, MD*;
Y Olefulobi, MD#; C Bradford, RN*; D Kucmeroski, BA#;
MG Mythen, MD#;
* Dept. of Anesthesiology - Box 1010, The Mount Sinai Medical Center,
New York, NY 10029
# Dept. of Anesthesiology - Box 3094, Duke University Medical Center,
Durham, NC 27710
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Introduction
+ All products currently used to replace intravascular volume
during surgury or trauma (e.g. albumin, crystalloid,
6% hetastarch in saline [NS]) have specific limitations.
+ A new version of 6% hetastarch, Hextend (BioTime, Inc.,
Berkeley, CA) uses a more physiologically balanced vehice than
6% hetastarch in NS. Compared with fluids routinely administered
for resuscitation, Hextend has been shown to improve survival in
preclinical studies and to have limited effects on coagulation
tests. [1-3]
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Methods
+ The primary aim of this study was to examine whether
the intraoperative administration of Hextend to patients
undergoing major elective surgery is safe and
effective when used in the treatment of hypovolemia.
+ Effective treatment was judged by the maintenance of
heart rate, blood pressure, and urine flow and by the volume of
fluid required to treat hypovolemia.
+ Safety was judged by comparing adverse events, blood
product utilization, and laboratory parameters in the two study
groups.
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Methods
+ Following Institutional Review Board approval and informed patient
consent, patients undergoing major elective surgery were enrolled
in a multicenter, prospective, randomized, blinded clinical trial.
+ Hextend or 6% hetastarch in NS was given to patients undergoing
surgery with general anesthesia according to a protocol.
+ Statistical analyses were carried out by a statistician using
accepted methodology. Non-pararmetric tests were used for
comparisons between study groups.
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Results
+ 120 patients were enrolled (n=60 at each site).
+ The study groups were well matched with respect to demographic
variables (Table 1). Duration of anesthesia was, on average,
over 5 hours (Table 2).
+ Postoperative hospitalization (mean days) was similar in the two
study groups (Hextend, 7.5 vs 6% hetastarch/NS, 8.4).
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Table 1 - Patient Demographics
6% Hetastarch/NS Hextend
------------------------------------------------------------
Age (years) 58.3 +/- 11.7 57.5 +/- 10.1
ASA class 2.4 +/- 0.5 2.4 +/- 0.5
Height (cm) 167.8 +/- 23.6 169.1 +/- 12.7
Weight (kg) 79.5 +/- 19.3 78.9 +/- 15.5
General Surgery (%) 21 21
Urologic Surgery (%) 10 8
Orthopedic Surgery (%) 0 1
Gynecologic Surgery (%) 18 21
Values are mean +/- SD where appropriate.
No significant differences (p>0.05) between groups for all variables.
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Results
+ Hemodynamic and coagulation related laboratory values are
presented in Table 2.
Of note:
+ Heart rate at the end of surgery was better maintained in the
Hextend treated patients.
+ Hemodynamic goals were achieved more commonly in Hextend treated
patients although this did not reach statistical significance.
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Table 2 - Hemodynamics and Coagulation
6% Hetastarch/NS Hextend
----------------------------------------------------------------
Hemodynamic goals met (%) 59 68
Duration of Anesthesia (min) 318 +/- 132 310 +/- 118
Urine output in OR (ml) 531 +/- 585 400 +/- 255
Heart rate - preop 78 +/- 13 76 +/- 10
Heart rate - postop * 82 +/- 10 77 +/- 16
Systolic BP - preop 137 +/- 23 139 +/- 25
Systolic BP - postop 135 +/- 21 133 +/- 21
Hematocrit - preop 36 +/- 6 36 +/- 4
Hematocrit - postop 31 +/- 6 31 +/- 5
Platelet count - preop 222 +/- 85 231 +/- 88
Platelet count - postop @ 174 +/- 75 163 +/- 74
PT - preop (min) 13.5 +/- 2.5 13.0 +/- 1.5
PT - postop (min) 17.0 +/- 6.7 16.3 +/- 4.5
PTT - preop (min) 31.9 +/- 7.3 30.2 +/- 4.5
PTT - postop (min) 44.4 +/- 30.5 42.9 +/- 30.8
Values are mean +/- SD where appropriate.
* = p=0.015 between groups.
@ = p<0.05 within Hextend group change.
No significant differences (p>0.05) between groups for all other
variables.
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Results
+ There was no significant difference in the volume of Hextend,
compared with 6% hetastarch in NS, required to effectively
treat hypovolemia (Table 3).
+ Hextend treated patients had lower EBL and were administered
less red blood cells, fresh frozen plasma, platelets, and
cryoprecipitate although this did not reach statistical
significance. this trend was consistent at both study sites.
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Table 3 - Fluids, Blood, & Blood Products Administerd in the
Operating Room (ml)
6% Hetastarch/NS Hextend
----------------------------------------------------------------
Study fluid 1428 +/- 1094 1596 +/- 923
Total fluids 2631 +/- 3275 2517 +/- 1959
Estimated blood loss (EBL) 1278 +/- 1617 1024 +/- 949
(Red blood cells + blood
products + study fluid)
- EBL 952 +/- 1160 1148 +/- 907
Crystalloid 402 +/- 1024 343 +/- 603
Red blood cells 642 +/- 1174 535 +/- 693
Fresh frozen plasma 122 +/- 471 38 +/- 149
Platelets 35 +/- 138 4 +/- 28
Cryoprecipitate 2 +/- 13 0 +/- 0
Values are mean +/- SD.
No significant differences (p>0.05) between groups for all variables.
Total fluids = red blood cells + blood products + study fluid +
crystalloid.
None of the patients received albumin intraoperatively.
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Results
+ Hextend treated patients had higher ionized calcium measurements
even though they required calcium therapy less often (Table 4).
+ 25 patients (42%) received more than 20 ml/kg of Hextend (maximum
volume administered = 5000 ml). Despite these large volumes, no
patient had an unexpected srious adverse event. Adverse events
are reported in Table 5.
+ There were fewer study-drug related bleeding complications in
Hextend treated patients.
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Table 4 - Calcium Measurements & Therapy
6% Hetastarch/NS Hextend p=
-------------------------------------------------------------------
Ionized Ca - Duke preop 5.30 +/- 0.36 5.23 +/- 0.28 NS
Ionized Ca - Duke postop 5.01 +/- 0.48 5.20 +/- 0.35 p=0.03
Ionized Ca - MSMC preop 1.21 +/- 0.05 1.18 +/- 0.04 NS
Ionized Ca - MSMC postop 1.12 +/- 0.06 1.14 +/- 0.05 p=0.03
# of patients administered
Calcium in OR (%) 6 (10%) 1 (1.7%) NS
Interoperative Ca dose (mg) 190 +/- 803 4 +/- 32 NS
Ca = calcium,
NS = p>0.05.
Values are mean +/- SD where appropriate.
Ca units are mg/dL at Duke and mmol/L at MSMC and were determined
using different methodologies at each study site.
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Table 5 - Adverse Events
6% Hetastarch/NS Hextend
-------------------------------------------------------------------
# of all adverse events @ 462 431
# serious adverse events @ 7 8
# patients w/ adverse events
related to study drug @ 8 3
# patients w/ coagulation related
adverse events related to study drug * 8 2
@ = No significant differences (p>0.05) between groups.
* = difference between groups in # of patients with study-drug related
coagulation adverse events (p=0.048).
Related to study drug = complications determined by independent
hematologist and clinical investigators prior to unblinding of study
to be possibly related to study drug.
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Conclusions
+ Compared with 6% hetastarch in saline, Hextend, was effective at
treating hypovolemia. In fact, treatment goals were more commonly
achieved and heart rate was better maintained in Hextend treated
patients.
+ Hextend was as safe as 6% hetastarch in saline as judged by the
incidence of adverse events.
+ These data suggest that Hextend has more favorable effects on
coagulation compared with 6% hetastarch in saline. This finding
warrants furter study.
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References
1. Kehrer S et al. hextend hemodilution improves survival over 6%
hetastarch in saline after stress. Experimental Biology 96th
Meeting, April 1996.
2. Abrams KJ et al. Evaluation of Hextend for resuscitation of
experimental hemorrhagic shock in dogs: a prospective, randomized,
controlled study. International Anesthesia Research Society
Meeting, 1996.
3. Bick RL. Evaluation of a new hydroxyethyl starch preparation
(Hextend) on selected coagulation parameters. Clin Appl Thrombosis/Hemostasis 1995; 1:215-29. |
