HextendT, a Physiologically Balanced Plasma Expander forLarge Volume Use in Major Surgery: A Randomized Phase IIIClinical Trial

T. J. Gan, MB, FRCA*, E. Bennett-Guerrero, MD†, B. Phillips-Bute, PhD*, H. Wakeling, MB, FRCA*,D. M. Moskowitz, MD†, Y. Olufolabi, MB*, S. N. Konstadt, MD†, C. Bradford, RN†,P. S. A. Glass, MD*, S. J. Machin, FRCP‡, M. G. Mythen, MD§, and the Hextendt Study Group1

*Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; †Department ofAnesthesiology, The Mount Sinai Medical Center, New York, New York; and Departments of ‡Haematology and§Anaesthesia, University College London Hospitals, London, England

Hextendt (BioTime, Inc., Berkeley, CA) is a new plasmavolume expander containing 6% hetastarch, balancedelectrolytes, a lactate buffer, and physiological levels ofglucose. In preclinical studies, its use in shock modelswas associated with an improvement in outcome com-pared with alternatives, such as albumin or 6%hetastarch in saline. In a prospective, randomized, two-center study (n 5 120), we compared the efficacy andsafety of Hextendt versus 6% hetastarch in saline (HES)for the treatment of hypovolemia during major surgery.Patients at one center had a blood sample drawn at thebeginning and the end of surgery for thromboelasto-graphic (TEG) analysis. Hextendt was as effective asHES for the treatment of hypovolemia. Patients re-ceived an average of 1596 mL of Hextendt: 42% re-ceived .20 mL/kg up to a total of 5000 mL. No patientreceived albumin. Hextendt-treated patients requiredless intraoperative calcium (4 vs 220 mg; P , 0.05). In asubset analysis of patients receiving red blood celltransfusions (n 5 56; 47%), Hextendt-treated patientshad a lower mean estimated blood loss (956 mL less;

P 5 0.02) and were less likely to receive calcium supple-mentation (P 5 0.04). Patients receiving HES demon-strated significant prolongation of time to onset of clotformation (based on TEG) not seen in the Hextendt pa-tients (P , 0.05). No Hextendt patient experienced arelated serious adverse event, and there was no differ-ence in the total number of adverse events between thetwo groups. The results of this study demonstrate thatHextendt, with its novel buffered, balanced electrolyteformulation, is as effective as 6% hetastarch in saline forthe treatment of hypovolemia and may be a safe alter-native even when used in volumes up to 5 L. Implica-tions: Hextendt (BioTime, Inc., Berkeley, CA) is a newplasma volume expander containing 6% hetastarch,balanced electrolytes, a lactate buffer, and a physiolog-ical level of glucose. It is as effective as 6% hetastarch insaline for the treatment of hypovolemia but has a morefavorable side effects profile in volumes of up to 5 Lcompared with 6% hetastarch in saline.

(Anesth Analg 1999;88:992–8)

T he etiology of postoperative morbidity is multi-factorial; however, occult hypovolemia isthought to be the most significant avoidable

cause of organ dysfunction and death (1,2). The ad-ministration of colloid as a plasma volume expanderduring the intraoperative period is associated withimproved outcome and reduction in hospital stay(3–5). The two commonly used colloids in NorthAmerica, 6% hetastarch in saline and 5% albumin havespecific limitations. The administrations of large vol-umes of 6% hetastarch in saline can cause coagulationabnormalities (6,7) and can lead to electrolyte imbal-ances, such as metabolic hyperchloremic acidosis, dueto the high chloride content. These concerns haveprompted cautious use of 6% hetastarch .20 mL zkg21 z d21. Albumin 5% is derived from plasma;hence, its availability depends on donor supply (8)and is associated with higher costs and potential risk

This study was supported in part by a grant from BioTime, Inc.The results of this study were presented in part at the American

Society of Anesthesiologists meeting, October 17–21, 1998, Orlando,FL.

Accepted for publication February 2, 1999.Address correspondence and reprint requests to T. J. Gan, MB,

FRCA, Department of Anesthesiology, Duke University MedicalCenter, Box 3094, Durham, NC 27710. Address e-mail togan00001@mc.duke.edu.

1 J. V. Booth, MB, FRCA, D.S. Bronheim, MD, C. Robertson, MD,D. E. Feierman, MD, D. Kucmeroski, BS, G. V. Gabrielson, S. Dufore,RN, I. H. Sampson, MD, K. M. Robertson, MD, S. B. Scarola, MD,A. B. Hilton, MD, W. J. Winfree, BSN, R. L. Woolf, MB, FRCA, andI. J. Mackie, MRCPath.

©1999 by the International Anesthesia Research Society992 Anesth Analg 1999;88:992–8 0003-2999/99

of viral contamination compared with 6% hetastarchin saline. Recently, albumin has been linked to in-creased mortality due to capillary leak syndrome andcoagulopathy (9,10).

Hextendt (BioTime, Inc., Berkeley, CA), a newpreparation of hydroxyethyl starch, is composed of 6%hetastarch (mean molecular weight 550 kD) in a solutionof electrolytes (Na1, K1, Ca21, Mg21, Cl2), physiologicallevels of glucose (90 mg/dL), and a lactate buffer that ismore likely to provide a more favorable acid-basebalance. Preclinical use of Hextendt in shock modelswas associated with an improvement in outcome com-pared with alternatives such as albumin or lactatedRinger’s solution (11). Recent in vitro studies of theeffects of Hextendt in human plasma have shownthat, at dilutions of up to 75% Hextendt and 25%human plasma, there were no adverse effects on he-mostatic variables except those expected by hemodi-lution (12). Immediately before the main study, sixpatients received Hextendt in an open-labeled study.Volumes of up to 3000 mL (1385 6 1116, mean 6 sd)were infused with no adverse effects related to thestudy drug (13).

In a prospective, randomized, double-blinded trial,we tested the hypothesis that the intraoperative ad-ministration of Hextendt to patients undergoing ma-jor elective surgery is as safe and effective as 6%hetastarch in saline when used for the treatment ofhypovolemia.

MethodsAfter institutional review board approval and written,informed patient consent, ASA physical status I–IIIadult patients presenting for major elective general,gynecological, orthopedic, or urological surgery withanticipated blood loss .500 mL were enrolled at DukeUniversity Medical Center (DUMC) and The MountSinai Medical Center. Patients with coagulopathy, sig-nificant hepatic (liver enzymes .50% upper limit ofnormal values) or renal (creatinine . 50% upper limitof normal values) dysfunction, congestive heart fail-ure; those who had received an investigational drugwithin the last 30 days; or with known hypersensitiv-ity to hydroxyethyl starches were excluded.

Patients were premedicated with midazolam andfentanyl. Before the induction of anesthesia, an IVbolus of 7 mL/kg lactated Ringer’s solution was ad-ministered, followed by an IV infusion of lactatedRinger’s solution at a rate of 5 mL z kg21 z h21, whichwas continued for the duration of anesthesia. Anes-thesia was induced by an IV technique and main-tained with a balanced inhalational technique incor-porating isoflurane, nitrous oxide, and oxygen withneuromuscular blockade supplied by IV vecuronium.Ventilation was adjusted to maintain Paco2 at

35–40 mm Hg, and temperature was maintained.35.5°C throughout surgery. If an epidural catheterwas placed as part of the patient’s postoperative care,a 3-mL test dose consisting of lidocaine 1.5% with1:200,000 epinephrine was administered, and no epi-dural local anesthetic drugs were administered intra-operatively. Anesthesia was maintained at a constantlevel as judged by standard clinical criteria.

In addition to the standard monitoring, direct arte-rial and central venous pressures were also monitored.All cardiovascular variables and urine flow were mon-itored and recorded during general anesthesia. Post-operatively, heart rate (HR), blood pressure, and uri-nary volumes were recorded every hour for 4 h, thenevery 4 h until 24 h after surgery. Types and volumesof all fluids administered intra- and postoperatively(including but not limited to crystalloid solutions,blood, and blood products) were recorded, as were thevolumes and doses of any drugs given during generalanesthesia and an estimation of blood loss.

Laboratory tests including hematocrit, plateletcount, serum electrolytes and creatinine, colloid on-cotic pressure, coagulation tests (e.g., prothrombintime, activated partial thromboplastin time), FactorVIIIc, and von Willebrand factors were measured be-fore induction, at the end of surgery, and on the dayafter surgery.

Patients at one center (DUMC) had a blood sampledrawn before induction and at the end of the surgicalprocedure for thromboelastographic (TEG) analysis,which provides a bedside dynamic measure of clotformation and takes into account the presence of co-agulation factors and cofactors (e.g., calcium) (14).Whole blood is placed in a cuvette, which is rotatedback and forth. A piston is suspended in the blood,and as coagulation proceeds, fibrin strands form be-tween the walls of the cuvette and the piston. Thepiston thus becomes increasingly coupled to the mo-tion of the cuvette; hence, the shearing elasticity of theevolving blood clot is detected to yield the TEG trace.The TEG variables for patients receiving ,20 mL/kgor $20 mL/kg of study solution are described inFigure 1.

Patients received either 6% hetastarch in saline orHextendt for the treatment of hypovolemia accordingto a hypovolemia algorithm (Figure 2). The intraoper-ative use of albumin was prohibited. The study solu-tions were prepared by the pharmacy in similar glassbottles to maintain blinding of groups. According tothis algorithm, hemodynamic targets included main-tenance of arterial blood pressure, HR, and urine out-put within a predefined range. Hemodynamic vari-ables triggering colloid dosing involved a urineoutput ,0.5 mL z kg21 z h21, a HR .20% above base-line or a HR .110 bpm, and systolic blood pressure(BP) ,20% below baseline or systolic BP ,90 mm Hg.If the central venous pressure (CVP) was , 15 mm Hg

ANESTH ANALG CARDIOVASCULAR ANESTHESIA GAN ET AL. 9931999;88:992–8 HEXTENDt PLASMA EXPANDER FOR MAJOR SURGERY

and the hematocrit was greater than 21% then a doseof colloid (either Hextendt or 6% hetastarch in saline)was administered until the hemodynamic target wasmet. If the CVP was $15 mm Hg, hypovolemia was aless likely cause of the abnormal hemodynamics; thus,consideration was given to further monitoring (i.e.,inserting a pulmonary artery catheter) or circulatorysupport with vasoactive drugs. In addition, patientsreceived 6% hetastarch in saline or Hextendt in vol-umes equivalent to that judged to be lost as a result ofsurgical hemorrhage. If the hematocrit was #21%,then blood was administered for the treatment ofhypovolemia instead of 6% hetastarch in salineor Hextendt. However, the clinicians administeredblood to a patient with a hematocrit .21% if clinicallyindicated; for example, if there was evidence of myo-cardial ischemia and anemia was thought to be acontributory cause.

After the administration of blood, the hematocritwas rechecked, and blood was given until the hemat-ocrit exceeded 21%. After the administration of eachcolloid dose, an assessment was made to determinewhether the hemodynamic goals had been met. If so,then the algorithm called for continued hemodynamicmonitoring. If a colloid dose did not result in restora-tion of the hemodynamic targets, then the CVP wasmeasured again to determine which limb of the algo-rithm was followed.

For the treatment of bleeding of a nonsurgical eti-ology, the protocol called for the administration ofblood products (platelets, fresh-frozen plasma, cryo-precipitate, or fibrinogen) when clinically indicatedand supported by the laboratory evidence of abnormalcoagulation: platelet count ,100,000/L, prothrombintime .1.5 times control, activated partial thrombintime .1.5 times control, and/or fibrinogen ,100mg/dL. Patients were extubated, either in the operat-ing room or postoperatively, when they fulfilled stan-dard clinical criteria. They were visited daily in theimmediate postoperative period for a maximum of5 days, until discharge or death. Patients who re-mained in the hospital for .5 days were visited againon the day of discharge. All adverse events and post-operative length of stay were recorded. In addition,adverse events were deemed coagulation-related if, inthe judgement of the investigators, abnormal lab-oratory values were associated with a nonsurgicalbleeding.

Data were analyzed to compare all patients in theprotocol group with all patients in the control groupon an intent to treat basis. The groups were comparedusing a t-test or Wilcoxon rank-sum test as appropri-ate. The volumes of IV colloid and calcium adminis-tered to the two groups were compared by using aone-way analysis of covariance adjusted for each pa-tient’s estimated blood loss. Incidence of adverse

Figure 1. Thromboelastographic variables at baseline and end of surgery (EOS) in the subgroups who received ,20 mL/kg or $20 mL/kgof study solution. *P 5 0.01 for change in baseline and EOS between Hextendt (BioTime, Inc., Berkeley, CA) and 6% hetastarch in saline. **P 5 0.03 for change in baseline and EOS between Hextendt and 6% hetastarch in saline. r time 5 the time from when the sample is put onthe thromboelastograph until the first significant levels of detectable clot formation. This is defined as the time when 2 mm of amplitude ofclot strength is detectable. k time 5 the time from beginning of clot formation to a fixed level of clot firmness (amplitude of 20 mm) is reached.MA 5 maximal amplitude. - -f- - 5 6% hetastarch ,20 mL/kg, –f– 5 $20 mL/kg, - -F- - 5 Hextendt ,20 mL/kg, –F– 5 Hextendt$20 mL/kg.

994 CARDIOVASCULAR ANESTHESIA GAN ET AL. ANESTH ANALGHEXTENDt PLASMA EXPANDER FOR MAJOR SURGERY 1999;88:992–8

events and intraoperative calcium administrationwere compared using a two-tailed Fisher’s exacttest. A P value ,0.05 was considered statisticallysignificant.

For estimation of sample size, the total volume ofcolloid (Hextendt or 6% hetastarch in saline) admin-istered by the end of surgery was taken as the primaryoutcome. Analysis of data from 207 patients undergo-ing similar types of surgery and anesthesia revealed amean 6 sd colloid equivalent volume transfused dur-ing surgery of 1821 6 540 mL. A sample size of 60 ineach group was calculated to have at least 80% powerto detect a difference in means of 30% given a commonstandard deviation of 540 mL using a two-group t-testwith a 0.05 two-sided significance.

ResultsOne hundred twenty patients were enrolled. Three pa-tients did not receive study solution (one did not requirecolloid treatment, one failed to have a central venouscatheter inserted, and one rescheduled surgery at shortnotice). The two groups were well matched with regardto demographics, preexisting disease, duration of anes-thesia, and type of surgery (Table 1). Patients in bothgroups received similar volumes of study drug (1596 mL

of Hextendt versus 1428 mL of 6% hetastarch) (Table 2).Twenty-one (35%) patients in the 6% hetastarch groupand 25 (42%) patients in the Hextendt group received.20 mL/kg study solution, with a maximal volumeinfused of 5000 mL in each group. No study patientreceived albumin intraoperatively.

Baseline hemodynamic variables were similar be-tween the two groups (Table 3). Although there wasno statistically significant difference in the change inHR, BP, and CVP between the two groups from base-line to end of surgery, there was a trend towardslower HR at the end of surgery (78 vs 82 bpm) and agreater increase in CVP (1.9 vs 20.4 mm Hg) inHextendt-treated patients. The difference in mean HRbecame statistically significant in a subset of patientswho received blood transfusion (78 vs 85 bpm; P 50.049). Hemodynamic goals as specified in the algo-rithm were achieved 63% (38 of 60) of the time in the6% hetastarch in saline group and 65% (39 of 60) of thetime in the Hextendt group. Postoperative hemody-namics and urine output were similar between thegroups, and there was no difference in the postoper-ative administration of fluids, blood, and bloodproducts.

There were no overall differences in the laboratory-measured hematological, biochemical and coagulation(Table 4) variables. Only one patient received paren-teral calcium supplementation intraoperatively in theHextendt group versus six patients in the controlgroup (mean intraoperative calcium 4.2 vs 220 mg;P , 0.05). Four patients experienced massive bloodloss (.70 mL/kg) during the procedure. Three ofthese four patients were in the 6% hetastarch in salinegroup. There was no difference between the twogroups in the incidence of overall adverse events. One

Figure 2. Algorithm for intraoperative colloid administration.BP 5 blood pressure, HR 5 heart rate, Hct 5 hematocrit, CVP 5central venous pressure.

Table 1. Patient Demographics

6%Hetastarch

(n 5 60)Hextendt(n 5 60)

Age (yr) 58 6 12 57 6 10Gender (M/F) 33/27 36/24ASA physical status

I 1 1II 32 35III 27 24

Height (cm) 171 6 8 169 6 13Weight (kg) 80 6 19 79 6 15Surgery type

General 26 25Gynecologic 12 10Orthopedic 0 1Urologic 22 24

Duration of anesthesia (min) 318 6 132 310 6 118Intraoperative fentanyl (mg) 858 6 480 928 6 488

Values are mean 6 sd.

ANESTH ANALG CARDIOVASCULAR ANESTHESIA GAN ET AL. 9951999;88:992–8 HEXTENDt PLASMA EXPANDER FOR MAJOR SURGERY

death that occurred on Day 34 in the Hextendt groupbut was not drug-related. The Hextendt patients’length of hospital stay averaged 7.5 days (versus8.4 days in the control group).

The percentage of patients who received bloodtransfusions intraoperatively and postoperativelywere similar: Hextendt 35 of 59 (59%), 6% hetastarchin saline 34 of 58 (59%). In a retrospective subgroupanalysis of patients who received a blood transfusionintraoperatively, estimated blood loss was signifi-cantly less in the Hextendt group (1560 mL vs2516 mL; P 5 0.02), and the number of patients requir-ing calcium administration intraoperatively (1 of 31 vs6 of 25; P 5 0.04) was also significantly smaller. Con-sistent with reduced blood loss, the Hextendt group

seemed to require less blood and blood products(Table 5).

Patients who received 6% hetastarch in saline exhib-ited an overall significant slowing of the onset of clotformation (r time) during surgery, compared withthose receiving Hextendt (P , 0.05). When TEG trac-ings were analyzed with respect to the volume of testsolutions administered (,20 mL/kg and $20 mL/kg),this difference was more pronounced in the 6%hetastarch group (Figure 1). Other TEG variables weresimilar between the two groups.

DiscussionWe designed this study to determine the efficacy andsafety of Hextendt compared with 6% hetastarch insaline. The results of this study demonstrate thatHextendt is effective for the treatment of hypovole-mia. Furthermore, numerous findings from this studysuggest that Hextendt is a safe alternative.

The administration of colloid as plasma volumeexpander during the intraoperative period may beassociated with an improved outcome. Mythen andWebb (3) demonstrated a reduction in the incidence ofmajor complications and hospital stay in elective car-diac surgery patients who received perioperativeplasma volume expansion with colloid. Similar resultswere shown by Sinclair et al. (4), who studied the

Table 2. Intraoperative Administration of Fluids,Blood, and Blood Products and Estimated Blood Loss

6%Hetastarch

(n 5 60)Hextendt(n 5 60)

Volume of study fluid (mL) 1428 6 1094 1596 6 923Lactated Ringer’s solution

(mL)2782 6 1219 2926 6 1249

Other crystalloids (mL) 402 6 1024 342 6 603Red blood cells (mL) 642 6 1174 538 6 694Fresh–frozen plasma (mL) 122 6 471 38 6 149Platelets (mL) 35 6 138 4 6 28Cryoprecipitate (mL) 2 6 13 0Estimated blood loss (mL) 1278 6 1616 1024 6 949

Values are mean 6 sd.

Table 3. Intraoperative Hemodynamics Variables

6%Hetastarch

(n 5 60)Hextendt(n 5 60)

HR (bpm)Baseline 78 6 13 76.3 6 10EOS 82 6 10 77 6 16Change 3 6 14 1 6 13

SBP (mm Hg)Baseline 137 6 23 139 6 25EOS 135 6 21 133 6 21Change 22 6 22 25 6 25

DBP (mm Hg)Baseline 71 6 10 73 6 13EOS 72 6 10 72 6 11Change 1 6 10 21 6 13

CVP (mm Hg)Baseline 12 6 5 10 6 4*EOS 11 6 6 12 6 5Change 20.4 6 6 1.9 6 5†

Urine flow (mL z kg21 z h21) 1 6 1 1 6 1

Values are mean 6 sd.HR 5 heart rate, SBP 5 systolic blood pressure, DBP 5 diastolic blood

pressure, CVP 5 central venous pressure, EOS 5 end of surgery. Numbersare mean 6 sd.

* P 5 0.03.† P 5 0.02.

Table 4. Intraoperative Hematocrit and CoagulationVariables

6%Hetastarch

(n 5 60)Hextendt(n 5 60)

Hematocrit (%)Baseline 35.7 36.2EOS 31.0 31.3

PT (s)Baseline 14 6 2 13 6 2EOS 17 6 7 16 6 4

APTT (s)Baseline 32 6 7 30 6 5EOS (s) 44 6 30 43 6 31

Factor VIII (IU/L)Baseline 1.4 6 0.7 1.2 6 0.6EOS 1.4 6 0.9 1.2 6 0.9

vWF (IU/L)Baseline 1.6 6 0.9 1.3 6 1EOS 1.4 6 1 1.1 6 0.6

Platelet (31029/L)Baseline 214 6 75 226 6 74EOS 175 6 75 160 6 72

Fibrinogen (IU/L)Baseline 2.9 6 1.2 2.9 6 1.3EOS 1.8 6 1.4 1.8 6 1.6

Values are mean 6 sd.EOS 5 end of surgery, PT 5 prothrombin time, APTT 5 activated partial

thromboplastin time, vWF 5 von Willebrand factor.

996 CARDIOVASCULAR ANESTHESIA GAN ET AL. ANESTH ANALGHEXTENDt PLASMA EXPANDER FOR MAJOR SURGERY 1999;88:992–8

effect of fluid optimization with colloid in elderlypatients undergoing repair of a proximal femoral frac-ture. There was a 39% reduction in hospital stay in thecolloid treatment group.

Although 6% hetastarch in saline is effective in ex-panding plasma volume, its use has been associatedwith side effects, notably coagulation abnormalities,when large volumes are used (15,16). This prompted alabeling statement cautioning the use of .20 mL zkg21 z d21. In this study, 35% of patients inthe 6% hetastarch group and 42% of patients in theHextendt group received more than the 20-mL/kgrecommendation.

Numerous findings in this study suggest thatHextend® has a favorable side effect profile. Only onepatient received parenteral calcium supplementationintraoperatively in the Hextendt group, versus sixpatients in the control group. There were trends to-ward there being less bleeding in the Hextendt group,as judged by estimated blood loss and the requirementfor blood products. These trends were observed atboth study sites for red blood cell, platelets, fresh-frozen plasma, and cryoprecipitate transfusions. Sev-eral of these differences became more pronounced inthe subset of patients in which one would expect toobserve a larger drug effect, i.e., patients receivingintraoperative blood transfusions and patients receiv-ing .20 mL/kg study fluid. The Hextendt-treatedgroup demonstrated a significantly better TEG dy-namic clot formation (P , 0.05), which was moremarked in the subgroup who received $20 mL/kg.

Based on the laboratory coagulation tests, there isno obvious explanation for the decreased blood loss,need for blood products, and coagulation-related ad-verse events noted in Hextendt patients. The differ-ence in dose-dependent changes in factor VIII and vonWillebrand factor previously observed with highermolecular weight starches (7) were not seen in either

group. One possible explanation may lie in the differ-ences in ionized calcium, as calcium is essential to thepathways underlying effective clot formation.Hextendt contains calcium levels similar to those nor-mally found in blood (10 mg/dL), whereas 6%hetastarch in saline contains none. Moreover, this sup-position is supported by the observation that, in pa-tients who received red blood cell transfusions, therewas a mean difference in estimated blood loss of ap-proximately 1 L. The transfusion of citrated red bloodcells may have been associated with a more profoundbut transient reduction in plasma calcium levels in thepatients receiving large amounts of calcium-free 6%hetastarch in saline as opposed to Hextendt (17). Arapid (within 5 min) infusion of 750 mL of citrated redblood cells has been shown to induce up to a 41%acute decline in ionized calcium (18). This transientreduction in ionized calcium may have lead to lesseffective clotting at the cut tissue edge. BecauseHextendt is also lower in chloride (which thereforereduces acidosis secondary to this chloride burden)and is buffered with lactate, a more favorable local-ized and acute acid-base balance may also prevail inthese patients relative to controls, further facilitatingclotting (19).

The TEG studies conducted at DUMC provided fur-ther evidence consistent with coagulation-related ab-normalities in the patients given 6% hetastarch in sa-line. The r times were significantly increased duringsurgery in these patients compared with the Hextendtpatients, which suggests that the onset of clot forma-tion became delayed in the 6% hetastarch in salinegroup. This difference became more pronounced inthe subgroup who received $20 mL/kg. The r timecorrelates with initial fibrin formation and is related tooverall activity of clotting factors, which could beinfluenced by local calcium concentration (14).

Our findings in this study indicate that Hextendt isas effective as 6% hetastarch in saline when used forthe treatment of hypovolemia. Numerous findingssuggest that Hextendt has a favorable side effectsprofile. Furthermore, there were no serious adverseevents related to the administration of Hextendt involumes of up to 5 L. With its buffered, balancedelectrolyte formulation, Hextendt seems to be a safealternative to 6% hetastarch in saline.

References1. Mythen MG, Webb AR. Intra-operative gut mucosal hypoper-

fusion is associated with increased post-operative complicationsand cost. Intensive Care Med 1994;20:99–104.

2. Mythen MG, Webb AR. The role of gut mucosal hypoperfusionin the pathogenesis of post-operative organ dysfunction. Inten-sive Care Med 1994;20:203–9.

3. Mythen MG, Webb AR. Perioperative plasma volume expan-sion reduces the incidence of gut mucosal hypoperfusion duringcardiac surgery. Arch Surg 1995;130:423–9.

Table 5. Intraoperative Administration of Blood, BloodProducts, and Estimated Blood Loss in a Subset of PatientsWho Received Red Blood Cell Transfusions

6%Hetastarch

(n 5 25)Hextendt(n 5 31)

Volume of study fluid (mL) 2186 6 1223 2066 6 942Lactated Ringer’s solution

(mL)3204 6 1240 3186 6 1394

Other crystalloids (mL) 925 6 1425 634 6 713Red blood cells (mL) 1516 6 1397 1040 6 639Fresh-frozen plasma (mL) 288 6 697 73 6 202Platelets (mL) 83 6 205 7 6 38Cryoprecipitate (mL) 4 6 20 0Estimated blood loss (mL) 2516 6 1856 1560 6 999*

Values are mean 6 sd.* P 5 0.02.

ANESTH ANALG CARDIOVASCULAR ANESTHESIA GAN ET AL. 9971999;88:992–8 HEXTENDt PLASMA EXPANDER FOR MAJOR SURGERY

4. Sinclair S, James S, Singer M. Intraoperative intravascular vol-ume optimisation and length of hospital stay after repair ofproximal femoral fracture: randomised controlled trial. BMJ1997;315:909–12.

5. Gan TJ, Arrowsmith JE. The oesophageal Doppler monitor[editorial]. BMJ 1997;315:893–4.

6. Cope JT, Banks D, Mauney MC, et al. Intraoperative hetastarchinfusion impairs hemostasis after cardiac operations. AnnThorac Surg 1997;63:78–82.

7. Kuitunen A, Hynynen M, Salmenpera M, et al. Hydroxyethylstarch as a prime for cardiopulmonary bypass: effects of twodifferent solutions on haemostasis. Acta Anaesthesiol Scand1993;37:652–8.

8. Macintyre E, Bullen C, Machin SJ. Fluid replacement in hy-povolaemia. Intensive Care Med 1985;11:231–3.

9. Offringa M. Excess mortality after human albumin administra-tion in critically ill patients. BMJ 1998;317:223–4.

10. Reviewers CIGA. Human albumin administration in critically illpatients: systemic review of randomised controlled trials. BMJ1998;317:235–40.

11. Nielsen VG, Tan S, Brix AE, et al. Hextend (hetastarch solution)decreases multiple organ injury and xanthine oxidase releaseafter hepatoenteric ischemia-reperfusion in rabbits. Critical CareMed 1997;25:1565–74.

12. Bick RL. Evaluation of a new hydroxyethyl starch preparation(Hextend) on selected coagulation parameters. Clin ApplThrombos Hemostas 1995;1:215–29.

13. Woolf R, Gan TJ, Cooper A, et al. An open label study ofHextendt, a new physiologically balanced colloid. In: Proceed-ings of the Association of Cardiothoracic Anaesthetists, 1997.

14. Mallett SV, Cox DJA. Thromboelastography. Br J Anaesth 1992;69:307–13.

15. Stump DC, Strauss RG, Henriksen RA, et al. Effects of hydroxy-ethyl starch on blood coagulation, particularly factor VIII.Transfusion 1985;25:349–54.

16. Lockwood DN, Bullen C, Machin SJ. A severe coagulopathyfollowing volume replacement with hydroxyethyl starch in aJehovah’s Witness. Anaesthesia 1988;43:391–3.

17. Zaloga GP. Hypocalcemia in critically ill patients. Crit Care Med1992;20:251–62.

18. Denlinger JK, Nahrwold ML, Gibbs PS, Lecky JH. Hypocalcae-mia during rapid blood transfusion in anaesthetized man. Br JAnaesth 1976;48:995–1000.

19. Egli GA, Zollinger A, Seifert B, et al. Effect of progressivehaemodilution with hydroxyethyl starch, gelatin and albuminon blood coagulation. Br J Anaesth 1997;78:684–9.

998 CARDIOVASCULAR ANESTHESIA GAN ET AL. ANESTH ANALGHEXTENDt PLASMA EXPANDER FOR MAJOR SURGERY 1999;88:992–8