|Year : 2015 | Volume
| Issue : 3 | Page : 349-354
The effect of 6% hydroxyethyl starch 130/0.4 on hemodynamic efficacy and hemostasis in major orthopedic surgery: a comparison with 6% hydroxyethyl starch 200/0.5
Hannaa F.M. Salama MD , Mohamad A Ameen, Mostafa A Aziz
Department of Anesthesia and Intensive Care, Faculty of Medicine-Al Azhar University, Cairo, Egypt
|Date of Submission||06-May-2014|
|Date of Acceptance||16-Jun-2014|
|Date of Web Publication||29-Jul-2015|
Hannaa F.M. Salama
Department of anesthesia and Intensive care, Faculty of Medicine-Al Azhar University, Cairo
Source of Support: None, Conflict of Interest: None
Clinical trial on patients undergoing major orthopedic surgeries to assess the safety and efficacy of 6% hydroxyethyl starch (HES) 130/0.4 (voluven) in comparison with 6% HES (200/0.5).
Patients and methods
A total of 40 patients scheduled for major orthopedic surgery were randomized to receive either 6% HES 130/0.4 (voluven group) or 6% HES 200/0.5 (haesteril group) during the intraoperative period. Amount of given colloids and crystalloids, blood loss, and the number of patients who needed blood transfusion were recorded. Mean blood pressure and heart rate were recorded at four time points during the operation. Laboratory measurements included hemoglobin, platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, and factor VIII concentrations. They were recorded before the surgery (baseline) and at 6 and 24 h after the surgery.
Mean blood pressure and heart rate were comparable between both groups. There was equivalence of mean infused volumes of voluven and haesteril during the study period (P = 0.086). The intraoperative blood loss was significantly lower in the voluven group than in the haesteril group (P = 0.001), and a smaller number of patients in the voluven group required blood transfusion compared with the haesteril group (P = 0.023). Hemoglobin and platelets decreased significantly at 6 and 24 h after surgery compared with the baseline values, with insignificant difference between both groups. Prothrombin time increased significantly at 6 and 24 h after surgery in both the groups. The increase was significantly more in the haesteril group. Activated partial thromboplastin time increased significantly in the haesteril group at 6 and 24 h after surgery, whereas there was a nonsignificant change in the voluven group. Factor VIII concentration showed a significantly larger increase at 6 and 24 h after surgery in the voluven group than in the haesteril group.
In surgeries with major blood loss, voluven has a comparable efficacy to haesteril and may reduce coagulation impairment, possibly leading to less requirements of allogenic blood transfusion.
Keywords: blood loss, coagulation, haesteril, major orthopedic surgery, voluven
|How to cite this article:|
Salama HF, Ameen MA, Aziz MA. The effect of 6% hydroxyethyl starch 130/0.4 on hemodynamic efficacy and hemostasis in major orthopedic surgery: a comparison with 6% hydroxyethyl starch 200/0.5. Ain-Shams J Anaesthesiol 2015;8:349-54
|How to cite this URL:|
Salama HF, Ameen MA, Aziz MA. The effect of 6% hydroxyethyl starch 130/0.4 on hemodynamic efficacy and hemostasis in major orthopedic surgery: a comparison with 6% hydroxyethyl starch 200/0.5. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2020 Feb 21];8:349-54. Available from: http://www.asja.eg.net/text.asp?2015/8/3/349/161697
| Introduction|| |
Adequate maintenance of intravascular volume is an important factor in managing surgical patients  . Colloids are effective plasma expanders often used for intravascular volume replacement in patients undergoing major surgery , . Hence, colloids are widely used in fluid resuscitation, and hydroxyethyl starch (HES) has especially become an established approach to correct hypovolemia under a variety of conditions  . They are frequently used as an alternative for blood loss replacement to restore intravascular volume and avoid the risk associated with transfusion of allogenic blood  . HES preparations may differ in mean molecular weight (MW), degree of molar substitution (hydroxyethyl group number per mole glucose subunit), C2/C6 ratio (pattern of hydroxylation at C2/C6), or solvent (saline based or balanced)  . Molar substitution and C2/C6 ratio mainly determine the rate of HES degradation by serum amylase, whereas MW is considered less important  . HES can significantly affect blood coagulation. This was more often present with first-generation solutions, which had higher MW and higher degree of substitution. When these solutions are administered in high volume, they may cause platelet dysfunction by reducing availability of the functional receptor for fibrinogen on the platelet surface (GPII-HA) in greater proportion than that expected only by simple plasma dilution , . Reduction in MW and molar substitution have led to products with shorter half-lives, improved pharmacokinetic and pharmacodynamic properties, and fewer side effects  .
Pentastarch as HES 200/0.5 is a second-generation HES, which was used as a standard in intravascular volume therapy for many years. HES 130/0.4 (voluven) and HES 130/042 (venofundin) are the latest third-generation tetrastarches. Voluven is a waxy maize amylopectin, with an MW 130 000 Da, an MS 0.4, and C2/C6 ratio of about 9.1. It also has the advantages of a higher plasma-expanding effect with fewer effects on coagulation  .
This study was conducted to compare the volume efficacy, intraoperative blood loss, blood transfusion requirements, and effects on the coagulation parameters of voluven and haesteril in patients undergoing major orthopedic surgery under general anesthesia.
| Patients and methods|| |
The study was approved by the local ethics committee and was conducted at Al-Zahraa University Hospital. Written informed consent was obtained from each patient.
A total of 40 adult patients of both sexes scheduled for elective major orthopedic surgery with expected blood loss of more than 15% of total blood volume were included in the study. Exclusion criteria were ASA physical status >II, hemoglobin (Hb) less than 10 g/dl cardiac insufficiency (New York Heart Association >II), significant liver disorders (bilirubin >1.5 times the upper limit of normal), renal dysfunction (serum creatinine >1.3 mg/dl), coagulation abnormalities, preoperative anticoagulant, or NSAID therapy (within 5 days before surgery).
Patients were randomly assigned to receive either 6% HES 130/0.4 (voluven group, n = 20) or 6% HES 200/0.5 (haesteril group, n = 20) as volume-replacement therapy during surgery. All products were from Fresenius Kabi (Bad Homburg, Germany). The maximum dose of voluven or haesteril was 33 ml/kg. This is the maximum dose that is approved for HES in Europe  .
After positioning on the operating table, standard monitoring was connected to all patients. They were monitored for noninvasive blood pressure, ECG, peripheral oxygen saturation, end-tidal carbon dioxide, and urine output (indwelling urinary catheter). All patients were administered general anesthesia, which was induced with propofol 1.5-2 mg/kg and fentanyl 1-1.5 µg/kg. Muscle relaxation for tracheal intubation was achieved with cisatracurium 0.15 mg/kg. Anesthesia was maintained with isoflurane 1-1.5% in 50% oxygen in air and intermittent doses of fentanyl and cisatracurium as appropriate. After tracheal intubation, mechanical ventilation was adjusted to maintain normocapnia (end-tidal carbon dioxide of about 35-40 mmHg).
All patients received Ringer lactate routinely at a rate of 8-10 ml/kg/h to cover the fluid deficit from the fasting period and basal fluid requirement.
Administration of colloids started after the induction of anesthesia and ended at the end of surgery. During this period, the triggers for the infusion of voluven or haesteril were a systolic blood pressure of less than 90 mmHg or a decrease of more than 20% from baseline, a heart rate (HR) of greater than 100 bpm or an increase of more than 30% from baseline, or a urine output less than 0.4 ml/kg/min. Colloid and crystalloid infusions were tailored according to intraoperative hemodynamic variables [HR, mean arterial pressure (MAP)], estimated blood loss, and clinical status.
Blood loss was measured by monitoring blood accumulated in the suction container and the number of towels used. The patients underwent red blood cell transfusion if Hb became less than 8 g/dl and 1 U of fresh-frozen plasma for each 4 U of red blood cells, or if diffuse oozing appeared in the surgical field.
Surgery times, intraoperative replacement therapy including crystalloids, colloids, and blood and plasma transfusions in addition to urine output were recorded in the intraoperative period.
HR and MAP were recorded before the induction of anesthesia (T1), after the induction of anesthesia before any colloid infusion (T2), after the end of infusion (T3), and at the end of operation (T4).
Blood samples were taken at the following timings: 1 day before the surgery (baseline), at 6 h after the surgery, and at 24 h after the surgery. Each sample was assessed for Hb, platelet count (Symex KX21, Symex Dade Behring Ca500 Norderstedt-Germany, Epi-info, Georgia, USA), prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, and factor VIII concentrate (Sysmex Dade Behring CA500 series apparatus).
The sample size was calculated using Epi-Info program version 7 by adjusting power of the test to 80% and the confidence interval to 95%, with margin of error accepted to 5%. The data were collected, coded, revised, and entered in the Statistical Package for Social Science version 17 (SPSS Inc., Chicago, Illinois, USA), and it was presented as numbers, percentage, mean, SDs, and ranges. The comparison between the two groups with qualitative data was made by using χ2 -test, whereas the comparison between the two groups with quantitative data and normally distributed was made by using independent t-test and also the comparison inside the same group was made using paired t-test. The confidence interval was set to 95% and the margin of error accepted was set to 5%. Therefore, the P-value was considered significant at the level of less than 0.05.
| Results|| |
The patients in both groups were comparable with regard to their demographics, type, and duration of surgery [Table 1].
Hemodynamic variables (MAP and HR) displayed similar changes between successive observation time points during anesthesia in the two groups [Table 2].
Fluid input and output balances are summarized in [Table 3]. There was no statistically significant difference between the volumes of crystalloid and colloid administered to patients in the two groups. The urine output was also similar. Intraoperative blood loss was significantly less in the voluven group than in the haesteril group. The number of patients who need blood transfusion was significantly lower in the voluven group compared with the haesteril group.
There was a significant decrease in the Hb concentration and platelet count in both groups at 6 and 24 h after surgery compared with baseline values, with insignificant difference in between groups [Table 4].
PT increased significantly at 6 and 24 h after surgery compared with the baseline values in both groups. In between groups, there was a significant increase in PT value at 6 and 24 h after surgery in the haesteril group compared with the voluven group [Table 4].
With regard to aPTT, there was a nonsignificant difference at different times of the study in the voluven group. In the haesteril group, aPTT mean values increased significantly with time (at 6 and 24 h) when compared with the baseline value. In group comparison, aPTT increased significantly at 24 h after surgery compared with the voluven group.
There were significant differences with time with regard to the fibrinogen level compared with the baseline values in the voluven and haesteril groups.
Fibrinogen level decreased significantly at 6 and 24 h after surgery compared with the baseline values in the voluven and haesteril groups. In between groups, fibrinogen showed nonsignificant difference at 6 and 24 h after surgery.
Factor VIII concentration decreased significantly at 6 h after surgery in both the groups compared with the baseline value, and after recovery its level increased significantly at 24 h after surgery compared with the baseline value. In between groups, factor VIII concentration showed a significantly larger mean increase in the voluven group than in the haesteril group at 24 h after surgery.
| Discussion|| |
This study was designed to investigate the clinical efficacy and safety between a novel 6% HES 130/0.4 (voluven) and a standard 6% HES 200/0.5 (haesteril) in major orthopedic surgery with respect to correction of intraoperative hypovolemia and maintenance of hemodynamic stability. The primary efficacy end-point was the colloid volume infused. Safety evaluation focused on the effect on coagulation parameters, estimated blood loss, and blood transfusion requirements.
Elective major orthopedic surgery was chosen because it offers frequent and standardized surgical settings, allowing the study design to be based largely on clinical routine. The results were not influenced by different crystalloid use, as crystalloid volumes infused were similar in both groups.
It was found in our study that the mean volumes of both colloids infused after the induction of anesthesia till the end of surgery were comparable. The efficacy of plasma volume substitution by voluven and haesteril has been demonstrated to be comparable in several studies. Sander et al.  compared voluven and haesteril for volume-replacement therapy in female patients undergoing major gynecological surgery. They found that the total volume of colloids required during surgery and up to 5 h after the end of surgery did not differ between groups. Gallandat Huett et al.  reported that comparable volumes of voluven and haesteril were required in cardiac surgery patients for hemodynamic stabilization until 16 h after end of surgery. These results were confirmed by Langeron et al.  in patients undergoing orthopedic surgery where equal volumes of both colloids were required for hemodynamic stabilization until 5 h after the end of surgery. A second study on orthopedic surgery patients  yielded comparative results, showing that equal volumes of both colloid solutions were used for hemodynamic stabilization until the first postoperative day. The same study showed that colloid osmotic pressure could be similarly maintained in both groups. These results can be explained by the fact that colloid osmotic pressure does not directly depend on HES concentration, but on the number of oncotically active particles. As HES 130/0.4 was more rapidly excreted and the in-vivo MW of HES 130/0.4 was found to be significantly lower compared with HES 200/0.5, more macromolecules per gram were available for HES 130/0.4, thus compensating for the more rapid excretion.
In the present study, patients in the voluven group had significantly less intraoperative blood loss with less need for blood transfusion compared with patients in the haesteril group. In addition, factor VIII concentration and aPTT were significantly less compromised by voluven than by haesteril in the early postoperative phase. These two coagulation variables are relevant for the evaluation of any new HES type, as it is known that higher substituted and high MW HES types lead to a prolonged PTT and a low postoperative increase in factor VIII. HES macromolecules are known to interact with platelets and plasma coagulation factors such as factor VIII and von Willebrand factor (vWf), causing a decrease in the plasma levels of these factors and ultimately might lead to coagulation impairment in case of high doses of slow metabolized HES type  .
Similar results were obtained in previous clinical studies. Langeron et al.  described a significantly less reduced need for allogenic transfusion when comparing HES 130/0.4 with HES 200/05 infused at the same dose level. They found significantly less interference with factor VIII concentrate 5 h after the end of surgery in the HES 130/0.4 group.
In the study by Gallandat Huett et al.  6% HES 130/0.4 was compared with 6% HES 200/0.5 in coronary artery bypass (CAB) patients. Blood loss was found to be lower with lower need of blood transfusion in the HES 130/0.4 group compared with the HES 200/0.5 group. In addition, vWf increased to supernormal levels in both groups, but the increase was higher with HES 130/0.4. In a pooled analysis of 449 surgical patients comparing blood loss and transfusion requirements after HES 130/0.4 and HES 200/0.5, Kozeck-Langneckner et al.  found significant lower losses of red blood cells and less blood cell transfusions in HES 130/0.4 compared with HES 200/0.5. aPTT and vWf were significantly less influenced by HES 130/0.4 compared with HES 200/05. Kim et al.  designed a study to compare the effect of voluven and haesteril on hemostasis in patients undergoing off-pump CAB surgery. Blood tests including thromboelastography were measured at different times. They found that chest tube drainage at 16 h after the surgery was higher in the haesteril group than that in the voluven group. Maximum clot firmness was decreased in the HES group at sternal closure but not in the voluven group. They concluded that voluven may reduce postoperative blood loss compared with haesteril at the same dose level.
Tissue storage of HES depends on cumulative dose and exposure time  and more importantly on the HES type used  . Both tissue storage and plasma persistence should be minimized. Rapidly degradable HES 130/0.4 has the lowest tissue and plasma persistence of all known HES types. There are several studies concerning reduced tissue storage and a reduced influence on coagulation. Kasper et al.  conducted a study to compare the effect of high doses of up to 50 ml/kg of HES 130/0.4 and HES 200/0.5 (33 ml/kg) in CAB surgery with regard to effect on blood loss. They concluded that Haes 130/0.4 did not increase blood loss and transfusion requirements in CAB surgery compared with Haes 200/0.5 in a median dose of 33 ml/kg. High-dose infusion of HES 130/0.4 and HES 200/0.5 were also compared in a study by Neff et al.  in patients with severe head injury. Patients received either voluven at doses up to 70 ml/kg/day or haesteril at doses up to 33 ml/kg/day, followed by human albumin up to 70 ml/kg/day. No difference was observed in mortality, renal function, coagulation parameters, bleeding complications, or use of blood products.
| Conclusion|| |
This study showed that voluven and haesteril are equally effective plasma volume expanders, but voluven has a lesser effect on coagulation. In large blood loss surgery, voluven may have a favorable coagulation profile and may lead to a less blood transfusion compared with haesteril.
| Acknowledgements|| |
Conflicts of interest
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[Table 1], [Table 2], [Table 3], [Table 4]