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Pathophysiology and management of coagulation disorders in critical care
medicine
de Jonge, E.
Publication date 2000
Link to publication
Citation for published version (APA):
de Jonge, E. (2000). Pathophysiology and management of coagulation disorders in critical care medicine.
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Effectss of Different Plasma Substitutes on Blood
Coagulation.. A comparative review
Evertt de Jonge1 and Marcel Levi2
Departmentss of (1) Intensive Care and (2) Vascular Medicine, Academicc Medical Center, University of Amsterdam, The Netherlands
Abstract t
Objective:Objective: To compare the effects of different colloid plasma substitutes on
bloodd coagulation and post-operative blood loss.
DataData sources: Relevant studies were obtained from the medical literature. StudyStudy selection: Articles were selected that provided data on the effects of
colloidss on hemostasis and post-operative blood loss in humans. Studies comparingg different colloids were looked for using MEDLINE and by searching throughh the references of studies as they were collected.
DataData synthesis: Articles were reviewed and relevant data were extracted and
partlyy presented in comparative tables.
Conclusions:Conclusions: Dextran, gelatin and HES all can induce a specific decrease of von
Willebrandd factor and factor VIII:c. Blood coagulation is most impaired by dextrann and high molecular weight HES, both associated with increased post-operativee blood loss. The effects of HES on blood coagulation have been shown too depend on its molecular weight and rate of elimination. Detrimental effects havee been shown for HMW-HES and after repeated administration also for MMW-HESS with a high degree of substitution (HES 200/0.62) or MMW-HES withh high C2/C6 hydroxyethylation ratio (HES 200/0.5/13). Rapidly degradable HESS 200/0.5/6 and gelatin-based plasma expanders appear not to impair hemostasis.. However, based on the reviewed literature, all artificial colloids couldd potentially induce increased bleeding tendency after infusion of very large volumess and especially when given to patients with even mild forms of von Willebrandd disease. In those circumstances alternatives like plasma or albumin, althoughh associated with other serious complications, could be considered.
Introduction n
Syntheticc colloids are increasingly used as plasma substitutes in hypovolemicc patients because they are readily available, carry no risk of transmittingg viral or other plasma transfusion-related disease and are relatively inexpensive.. As these colloids are frequently used in bleeding patients or in situationss with a high risk of bleeding such as trauma or during surgery, there is somee concern regarding the effects of colloids on blood coagulation and platelet function.. In fact, all three distinct classes of artificial colloids (i.e. dextrans, hydroxyethyll starches and gelatins) have been associated with derangements of thee hemostatic system, although the clinical significance of these derangements
iss a matter of debate.1 Most evidence points to an impairment of coagulation by
plasmaa substitutes although some authors, referring to thromboelastography studies,, have suggested that hemodilution per se results in a hypercoagulable
state.2;33 These findings, however, have been disputed.4 In this review we will
focuss on the anti-hemostatic effects of artificial colloids and albumin on platelet functionn and blood coagulation.
Dextrans s
Dextranss are polydisperse glucose polymers produced by bacteria growingg in sucrose containing media. Commercially available dextran-based plasmaa substitutes have an avarage molecular weight of 40 or 70 kDa. Besides theirr plasma expanding properties they also exert an anticoagulant effect. Indeed,, dextrans have been shown to be effective in preventing post-operative
venouss thrombosis and pulmonary embolism.5"7 Dextran infusion induces a "von
Willebrandd syndrome" with decreased levels of von Willebrand factor (vWF)
andd associated factor VIII (VIIIx).8"10 The fall in vWF and factor VIIIx after
dextrann administration is more than can be explained by its dilutional effects. Vonn Willebrand factor is the ligand between the platelet surface receptor protein GPIbb and subendothelial collagen, thereby causing platelet adhesion to the vessell wall. Decreased levels of vWF therefore may lead to an impaired primary hemostasis.. Indeed, prolonged bleeding times were observed after infusion of
dextrann in animals11;l2 as well as in humans.13;14 The prolongation of bleeding
timee was totally reversed after increasing vWF levels by the intravenous administrationn of desmopressin (l-desamino-8-D-arginine vasopressin,
enhancee fibrinolysis.15*17 Earlier reports have suggested that fibrinolysis is increasedd by formation of complexes that include dextran, fibrin, plasminogen activatorr and <x-2 antiplasmin. Within these complexes dextran appears to protectt plasmin from the inhibitory effects of cc-2 antiplasmin. Indeed, clots formedd in the presence of dextran are relatively bulky in size, exhibit less
tensilee strength, and seem more easily disrupted.18"20 Recently, it has been shown
thatt fibrinolysis may rather be enhanced after dextran infusion by increased plasmaa concentrations of tissue type plasminogen activator (t-PA) and decreased concentrationss of the physiological inhibitor of fibrinolysis plasminogen
activatorr inhibitor-1 (PAI-1).'7
Afterr its administration, the anti-hemostatic effects of dextran on factor VIII/vWFF and fibrinolysis may result in an increased bleeding tendency. In clinicall studies comparing dextran with unfractionated heparin, low molecular weightt heparin or the heparinoid Orgaran as prophylaxis against venous thromboembolism,, dextran infusion resulted in increased post-operative blood
losss after transurethral prostatectomy21 or orthopaedic surgery2*23 and increased
thee need for blood transfusion after surgery for hip fracture.24 In a study
comparingg dextran with 4% albumin solution as intraoperative infusion fluid in orthopaedicc surgical patients who were also treated with LMWH thrombosis
prophylaxis,, patients treated with dextran needed more blood transfusions.25
Theree are no clinical studies comparing dextran with other synthetic colloid solutionss with respect to bleeding complications.
Gelatins s
Gelatinss are polydisperse polypeptides produced by degradation of bovine collagen.. Two separate forms are produced: succinylated (modified) gelatins, whichh have NH3 groups replaced by COO- groups by reaction of the basic peptidee with succinic acid anhydrase, and polygelines, consisting of polypeptidess crosslinked by urea-bonds. Although for a long time gelatins were
consideredd not to influence blood coagulation other than by dilution,26 there is
noww increasing evidence that gelatins do influence platelet function and blood coagulation.. In vitro blood coagulation in the presence of gelatin was studied usingg thromboelastography and scanning electron microscopy. Clots produced inn the presence of gelatin had decreased weight and strength and loss of the
confirmedd in another study using thromboelastography, this study also showed a moree modest increase in clot strength after dilution by gelatin as compared with
salinee dilution.28 Others have studied the effects of in vitro dilution of blood on
platelett aggegation. It was found that gelatin impaired aggregation induced by
ristocetinristocetin and polybrene.29 Agglutination tests induced by ristocetin and
polybrenee are specific for binding of vWF to the platelet receptor Gplb. These findingss are supported by the observation that in vivo administration of 1 liter of aa gelatin based plasma expander to healthy humans induced a von Willebrand likee syndrome with lengthening of bleeding time, impaired ristocetin-induced platelett aggregation and decreased levels of plasma vWF. It was suggested that vWFF binds to gelatin by means of its collagen binding site. Also a decrease in thrombinn generation, as measured by thrombin-antithrombin complexes and prothrombinn fragment F1+2, was observed after gelatin administration probably
causedd by hemodilution.30 The clinical relevance of the impairment of
hemostasiss after gelatin infusion is uncertain. Only one report suggests increased bloodd loss after cardiac surgery when gelatin instead of albumin was given
peroperatively.299 However, other studies comparing gelatin with HES31 or HES
andd albumin32 found no difference or in some cases even an improvement33 in
post-operativee blood loss when gelatin was given.
Hydroxyethyll starch
Hydroxyethyll starch (HES) is generally considered as an effective and safee plasma substitute. However, bleeding complications have been reported afterr administration of HES in various clinical settings. High molecular weight HESS (HMW-HES, Hetastarch, avarage MW 480.000 Da), which is the only HES solutionn that is approved in the United States as a plasma expander, has been
associatedd with increased post-operative bleeding after neurosurgery34 and in
patientss undergoing cardiac surgery.32;35;36 Furthermore, many case reports have
beenn published describing bleeding complications after HMW-HES in various
clinicall situations.37^*38"41 It has been suggested, that not all HES solutions have
negativee effects on blood coagulation, but that these effects depend on the averagee molecular weight of the HES molecules and its kinetics of elimination.
PharmacokineticsPharmacokinetics of HES
Naturall starches can not be used as plasma substitutes because they are rapidlyy degraded by circulating amylase and they are are insoluble at neutral pH. Hydroxyethyll starches are polymers of glucose units derived from amylopectin andd modified by substituting hydroxyethyl for hydroxyl groups on glucose molecules.. The substitution results in slower degradation and highly increased solubility.. HES are very polydisperse solutions of molecules with a broad range off molecular weights from very small to several hundred thousand Dalton. After administrationn of HES, the low molecular weight fraction is rapidly lost by renal eliminationn and the large molecules are progressively hydrolized, resulting in an averagee in vivo MW that is significantly lower than the average molecular weightt of the infused fluid. The rate at which degradation of HES molecules occurs,, depends on the degree of substitution (DS), that is the proportion of glucosee units having a hydroxyethyl group substituted for a hydroxyl group. Theree are three possible sites for substitution leading to a maximum DS of three. Currentlyy available HES solutions have a DS of 0.5 to 0.7. The rate of
degradationn and elimination is highest with low values for DS.1 Because
substitutionn is possible at positions 2,3 or 6 of the glucose unit, different patterns off substitution are possible. The substitution pattern is characterized by the C2/C66 hydroxyethylation ratio. Clearance of HES is slowest with high C2/C6
ratios.422 The characteristics of HES solutions are given by its initial molecular
weight,, the degree of substitution and the C2/C6 ratio. Thus, HES 200/0.5/6 has ann initial average MW of 200,000 Dalton, with 50% of glucose units having a hydroxyethyll group and with a C2/C6 ratio of 6 (i.e. 6 times more substitutions att the C2 position as compared with the C6 position).
EffectsEffects on factor VIII and von Willebrand factor
Studiess in healthy human volunteers have shown that circulating levels of factorr VIII and vWF decreased significantly after infusion of 0.5-1L of
HMW-HES433 or medium molecular weight HES (MMW-HES).44*5 Similar reductions
inn factor VIII and vWF have not only been found in healthy volunteers, but also
inn a number of clinical studies.37;46"51 Considerable insight in the influence of
HESS on blood coagulation come from observations by Treib et al. In several 10-dayss hemodilution experiments in patients, these authors found that a decrease inn vWF and factor VIII was only observed when MMW-HES was given that was
slowlyy degradable (i.e. with high degree of substitution and/or high C2/C6 ratio).. Those infusions resulted in accumulation of HES molecules with higher molecularr weights. It was concluded that the negative effects on hemostasis dependedd on the in vivo molecular weight,42;52;53 and that therapy with low-molecularr weight HES 70/0.5/4 or easily degradable MMW-HES 200/0.5/6 did nott inflence blood coagulation.54 However, we recently observed a 33% decreasee in vWF and 28% decrease in factor VIII after administration of 1 liter rapidlyy degradable HES 200/0.5/6 to healthy volunteers. These decreases were moree than could be explained by HES-induced plasma dilution. In accordance withh the diminished vWF levels, platelet adhesive function, measured by the platelett function analyzer PFA-100, was significantly prolonged after HES as comparedd to albumin 4% which is compatible with an aquired von Willebrand's syndromee (E. de Jonge et al, unpublished observations). A possible explanation forr these different findings in healthy volunteers as compared with the studies in patientss could be that vWF is an acute phase protein, increasing during acute illnesss and thereby potentially masking a concommitant HES-induced decrease. Furthermore,, relatively low quantities of HES were given during the hemodilutionn experiments by Treib et al. (1000 or 500 ml/day). In circumstances whenn large volumes of HES are given over a short time period (e.g. in bleeding patientss with circulatory shock), HES could potentially induce a clinically relevantt coagulation defect. Also, uncertainty exist about the clinical effect of thee administration of HES on blood coagulation in patients with already low circulatingg levels of vWF.
OtherOther markers of coagulation and fibrinolysis
Reductionss in the concentrations of other plasma coagulation factors, that couldd be fully ascribed to plasma dilution after administration of HES, have beenn reported repeatedly.50;53;55:56 The prothrombin time only slightly prolongs afterr the administration of HES, probably due to dilution of plasma factors.*43 Thee effects of HES on the activated partial thromboplastin time (aPTT) depends onn its molecular weight and the kinetics of elimination. Significant prolongation off the aPTT up to 40% has been described after repeated infusion of slowly degradablee MMW-HES 200/0.62/10. In contrast only a minimal prolongation wass found after the infusion of LMW-HES 70/0.5/4 or easily degradable MMW-HESS 200/0.5/6.42:45 A significant prolongation of the aPTT has also been found
afterr HMW-HES 480.37;43 The effects of HES on the aPTT can be readily explainedd by the specific decreases in factor VIII, potentially in combination withh some dilution of other plasma factors. HMW-HES 480 has been associated withh increased fibrinolysis. Hetastarch, but not MMW-HES, induced a significantt decrease of urokinase-activated clot lysis time. However, fibrin
monomerss and fibrin degradation products were not increased.5*57 Infusion of
5000 mL MMW-HES 200/0.5 in healthy voluntunteers did not result in changes inn plasma levels of tissue-type plasminogen activator (t-PA), urokinase-plasminogenn activator (u-PA), plasminogen activator inhibitor (PAI), plasmin-antiplasminn complexes (PAPc) or D-dimer when compared to infusion of albuminn 5%. The effects of HES on coagulation and fibrinolysis also have been studiedd using thromboelastography yielding results that are pointing in the same direction.. In vitro studies suggested prolonged clot formation time and increases
inn clot lysis after profound hemodilution with HES.58;59 Finally, HES might
affectt platelet function. Platelet volume decreases after infusion of HES, probablyy due to a shrinkage of platelets by the increased plasma colloid osmotic
pressure.422 It has however not yet been established whether the decrease in
platelett volume after HES administration affects platelet function and bleeding
time.. Prolonged bleeding times have been reported after HMW-HES57 and the
infusionn of MMW-HES has been associated with normal57 as well as prolonged
bleedingg times.2;33 In contrast, in another study comparing the influence of
MMW-HESS 200/0.5 and albumin on platelet aggregation no difference between
thee two colloids was observed.60
Albumin n
Albuminn is generally considered not to influence blood coagulation and is oftenn used as control fluid in studies evaluating the effects of other colloids. Indeed,, we recently found that infusion of 1L albumin 4% to healthy volunteers resultedd in only slightly diminished levels of fibrinogen and factor V, VII, VIII x andd vWF. These decreases could be completely explained by dilution of plasmafactorss by the infused fluid (E. de Jonge, unpublished observations). However,, it has been reported that albumin induces an impairment of platelet aggregationn and prolongation of bleeding time which observations could be
confirmedd in our study.61 ;62 The mechanism by which platelet function is
impairedd is uncertain. We did not find any report on an increased bleeding tendencyy related to the infusion of albumin.
Pathogenesiss of colloid-induced von Willebrand syndrome
Thee fact that all three classes of artificial colloids share the same vWF loweringg property may suggest that some common pathophysiologic mechanism exists.. This postulated common mechanism has not been fully elucidated yet. Noo change has been observed in the multimeric pattern of vWF after HES,
dextrann or gelatin infusion.10;30;63 It has been shown that the lowering effects of
thesee colloids on vWF antigen can not be reproduced in vitro.l0;30;43 Thus, it has
beenn suggested that colloids bind to vWF leading to accelerated in vivo
elimination.30;422 This mechanism has also been observed in patients with
monoclonall gammopathy who have an aquired form of von Willebrands disease
andd accelerated excretion of vWF-IgG paraprotein complex.42
Comparisonn of the different colloids with respect to blood coagulation
Studiess comparing different colloids in regard to laboratory markers of bloodd coagulation are summarized in table 1. Direct comparisons are difficult to makee as all studies differ in the plasma substitutes used, the amount of colloid infusedd and the population studied. Furthermore, some studies looked at effects off short-term fluid therapy (e.g. only during surgery) whereas others considered 10-dayy hemodilurion. Nevertheless, some general conclusions can be drawn. First,, the effects of HES on coagulation appear to depend on its molecular weightt as well as on the rate of in vivo degradation. High molecular weight HES undoubtedlyy affects blood coagulation even if given over a limited time period. Slowlyy degradable medium molecular weight HES (MMW-HES with high degreee of substitution or high C2/C6 hydroxyethylation ratio) also impairs coagulationn after repeated administration, probably due to accumulation of macromolecules.. In contrast, most studies consider easily degradable MMW-HESS (with low degree of substitution and low C2/C6 ratio) or LMW-HES to havee minimal influence if any on blood coagulation when compared to albumin. Thee effects of modified gelatin solutions appeared to be similar to the effects of easilyy degradable MMW-HES and albumin. An overview of studies comparing differentt colloids regarding post-operative blood loss is given in table 2. One singlee study found increased post-operative blood loss after dextran as compared withh albumin. Parallel to the observations on laboratory markers of coagulation, administrationn of HMW-HES may lead to increased blood loss. No study could findfind increased bleeding tendency after MMW-HES when compared to albumin, suggestingg that MMW-HES can safely be given during surgery.
Tablee 1. Overview of studies comparing the effects of different plasma substitutes on
laboratoryy markers of coagulation
Colloids s Studiess with HMW-HES Claess 19924* Brutocao, , 1996*4 4 6%% HES 450, 5% albumin n 6%% HES 450/0.5, 5% albumin n N= = 40 0 38 8 Population n Brainn tumor surgeryy or hysterectomy y Cardiac c surgeryy in children n Studiess with MMW-HES and low degree of substitution Beyerr 199731 Boldtt 1996*° Boldtt 1998" Kapiotiss 199445 Londonn 1989" London,, 1992s7 Rackoww 1989" Tigchetaar r 19974* * Vogtt 1996" 6%% HES 200/0.5, 3% modifiedd gelatin 10%% HES 200/0.5, 20%% albumin HESS 200/0.5, 20% albumin n HESS 200/0.5, 5% albumin n 10%% HES 264/0.45, 5%% albumin 10%% HES 264/0.45, 25%% albumin 10%% HES 245/0.45, 5%% albumin 10%% HES 200/0.5, 3%% modified gelatin, 5%% albumin HESS 200/0.5,5% albumin n 46 6 56 6 300 0 10 0 94 4 60 0 20 0 36 6 41 1 Major r orthopaedicc hip surgery y Traumaa or surgical l patientss with sepsis s Traumaa and sepsiss patients Healthy y volunteers, , cross-over r study y Cardiac c surgery y CABG G Sepsis s CABG G Totall hip replacement t Studiess with MMW-HES and high degree of substitution Treibb 1996" 10%% HES 200/0.5, 6%% HES 200/0.62 20 0 10-days s hemodilution n forr cerebral circulatory y disturbances s Amountt of colloid d 10000 ml Upp to 30 ml/kg g «25000 ml withinn 24 hr r ** 5L HES or3L L albuminn in 55 days ** 5L HES or2L L albuminn in 55 days 5000 ml ** 1800 ml 755 gram in priming g solution n ss 1000 ml Maximum m dose:: 3000 mll gelatin andd 20 ml/kgg HES ** 2500 ml 1000 0 ml/dayy on dayy 1-4, 5000 ml/day onn day 5-10 0 Parameters s studied d APTT,, PT, TT, Fbg,, VIIIx, vWF PT,, aPTT, TT, Fbg,, Platelets PT,, TT, Fbg, Platelets s Platelet t aggregation n inducedd by ADP, epinephrinee and collagen n Platelets,, AT HI, Fbg,, aPTT, PT Fbg,, aPTT, VIIIx,, TATc, D-dimer,, t-PA, u-PA,, PAI, PAPc PT,, aPTT, Platelets, , bleedingg time, Fbg,, factor V, VII,, VIH:c, IX PT,, aPTT, Platelets, , Bleedingg time, Fbg,, Factor VII, VIII,, IX. Platelets,, aPTT, PT,, Fbg, VIIIx, bleedingg time Platelet t aggregation n inducedd by ristocetinn and ADP,, in vitro bleedingg time, aPTT,, PT, vWF Platelets,, PT, aPTT,, TT, Fbg PT,, aPTT, TT, Fbg,, VIIIx, vWF Outcome e Diminishedd increase of VIIIxx and vWF after HMW-HES S Increasedd PT in children whoo received > 20 ml/kg HES S Noo difference Noo difference Noo difference Decreasedd levels of VIIIxx after HES
Noo difference
Increasedd aPTT after HESS (only immediately att end of bypass)
Decreasedd levels of VIIIxx after MMW-HES Decreasedd levels of vWF afterr MMW-HES and gelatin n
Noo difference
Progressivee prolongation off aPTT and decreased levelss of VIIIx and vWF afterr HES 200/0.62
Tablee 1, continued
Colloids s N= = Population n
Studiess with MMW-HES and high C2/C6 ratio Treibb 199552
Inn Vitro studies Eglii 1997s» Mardell 199669 Mortierr 1997s' Jamnicki i 199870 0 10%% HES 200/0.5/13,10% % HESS 200/0.5/6 6%% HES 200/0.5,4% modifiedd gelatin, 5% albumin,, 0.9% saline 3.5%% polygeline, 4% modifiedd gelatin, 0.9%% saline 6%% HES 200/0.5,4% modifiedd gelatin, 10%dextran40 0 6%% HES 130/0.4,6% HESS 200/0.5,0.9% NaCl l 20 0 96 6 20 0 11 1 80 0 10-days s hemodilution n forr cerebral circulatory y disturbances s Inn vitro experiments s Inn vitro experiments s Inn vitro experiments s Inn vitro experiments s Amountt of colloid d 1000 0 ml/dayy on dayy 1-4, 5000 ml/day onn day 5-10 0 300 or 60% dilution n 15-75% % dilution n 50% % dilution n 30%% and 60% % dilution n Parameters s studied d PT,, aPTT, TT, Fbg,, VIII:c, vWF Thromboelasto--graphy y
Clott weights and elasticityy by thromboelasto--graphy y Thromboelasto--graphy y Thromboelasto--graphy y Outcome e Increasedaflll and decreasedd levels of VIIIxx and vWF after HESS 200/0.5/13
Compromised d coagulationn parameters andd increased clot lysis afterr HES, gelatin and albumin.. Maximum effectt found with HES. Decreasedd clot weights andd elasticity after dilutionn by polygeline andd modified gelatin Increasedd clot formation timee and decreased maximumm amplitude afterr HES. Dilution with dextrann resulted in extremelyy compromised coagulation n
Comparablee decrease in coagulationn parameters andd increased clot lysis afterr both HES solutions
Studiess comparing gelatin with albumin or MMW-HES did find no difference, exceptt for one study that observed decreased blood loss after gelatin when comparedd to MMW-HES and one that found increased blood loss when
comparedd to albumin, but only in a sub-group also treated with aprotinin.29;33
Thus,, it appears that dextran and HMW-HES can induce an increased bleeding tendency,, whereas MMW-HES and gelatin are probably safe in this respect. Theree are, however, two major limitations to this conclusion. First, no studies havee addressed the risk of bleeding after repeated administration of colloids. Theoretically,, this could easily increase the risk of bleeding, especially with infusionn of slowly degradable HES. Second, these conclusions are probably only validd in subjects with normal levels of vWF or even increased levels due to the acutee phase response in acutely ill patients. All artificial colloids should be givenn cautiously to patients who are known with even mild forms of von Willebrandss disease, m those circumstances alternatives like plasma or albumin, althoughh associated with other serious complications, could be considered.
Tablee 2. Overview of prospective randomized clinical trials comparing post-operative blood
losss after different plasma substitutes.
Colloids s Dextrann vs. Albumin Lisander, , 1996" " Dextrann 70,5% albumin n HESS vs. Gelatin Boldtt 1993" Mortelmans s 1995" " Beyerr 199731 Tigchelaar r 199748 8 HMW-HESS 450/0.5, MMW-HESS 200/0.5, 3.5%% gelatin, 5% albumin n MMW-HESS 200/0.5, 3%% modified gelatin 6%% MMW-HES 200/0.5,, 3% modified gelatin n 10%% MMW-HES 200/0.5,, 3% modified gelatin,, 4% albumin HESS vs. Albumin Boldtt 1993" Brutocao, , 199664 4 Vogtt 1996" Londonn 198966 Londonn 1992" Tigchelaar r 1997" " Rosencher, , 1992" " HMW-HESS 450/0.5, MMW-HESS 200/0.5, 3.5%% gelatin, 5% albumin n 6%% HMW-HES 450/0.5,, 5% albumin MMW-HESS 200/0.5, albuminn 5% 10%% MMW-HES 264/0.45,, 5% albumin 10%% MMW-HES 264/0.45,25% % albumin n 10%% MMW-HES 200/0.5,3%% modified gelatin,, 4% albumin MMW-HESS 200/0.62, 4%% albumin Gelatinn vs. Albumin Tabuchii 199529 Wahba, , 1996" " Oxypolygelatin,, 4% albumin n Polygeline,, 5% albumin n N= = 40 0 60 0 42 2 46 6 36 6 60 0 38 8 41 1 94 4 60 0 36 6 16 6 60 0 20 0 Population n
Revisionn hip arthroplasty
CABG G
Totall hip replacement Majorr orthopaedic hip surgery y
CABG G
CABG G
Cardiacc surgery in children
Totall hip replacement
Afterr cardiac surgery
Cardiopulmonaryy bypass primingg solution
CABG G
Totall hip replacement
CABG G Cardiacc surgery Amountt of colloid »» 10 ml/kg 1190-14500 ml »20000 ml ** 2500 ml within first 244 hr Maximumm dose: 3000 mll gelatin and 20 ml/kgg MMW-HES 1190-14500 ml Upp to 30 ml/kg ** 2500 ml ** 1800 ml 755 gram Maximumm dose: 3000 mll gelatin and 20 ml/kgg MMW-HES 1500-20000 ml 20000 ml as priming solutionn for extracorporeall circuit Outcome e Increasedd blood losss and blood transfusionn after dextran n Increasedd blood losss after HMW-HES.. No difference e betweenn MMW-HESS and gelatin Increasedd blood losss after HES. Noo difference in bloodd loss and transfused d packedd red cells Noo difference in bloodd loss Increasedd blood losss after HMW-HES.. No difference e betweenn MMW-HESS and gelatin Noo difference in bloodd loss or numberr of packedd red cells transfused d Noo difference in bloodd loss or numberr of packedd red cells transfused d Noo difference in bloodd loss or numberr of blood transfusions s Noo difference in bloodd loss or numberr of blood transfusions s Noo difference in bloodd loss Noo difference in bloodd loss Increasedd blood losss after gelatin inn sub-group also treatedd with aprotinin n Noo difference in bloodd loss
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