Perfusion
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Comparison of low molecular weight hydroxyethyl starch and human albumin as priming solutions in children undergoing cardiac surgery Na Miao, Jing Yang, Zhongtao Du, Wei Liu, Hong Ni, Jialin Xing, Xiaofang Yang, Bo Xu and Xiaotong Hou Perfusion published online 21 March 2014 DOI: 10.1177/0267659114528267 The online version of this article can be found at: http://prf.sagepub.com/content/early/2014/03/21/0267659114528267
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528267 research-article2014
PRF0010.1177/0267659114528267PerfusionMiao et al.
Original paper
Comparison of low molecular weight hydroxyethyl starch and human albumin as priming solutions in children undergoing cardiac surgery
Perfusion 1–7 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0267659114528267 prf.sagepub.com
Na Miao, Jing Yang, Zhongtao Du, Wei Liu, Hong Ni, Jialin Xing, Xiaofang Yang, Bo Xu and Xiaotong Hou
Abstract Human albumin is the conventional cardiopulmonary bypass circuit primer. However, it has high manufacturing costs. Crystalloid and colloid solutions have been developed as alternatives, including a new generation of non-ionic hydroxyethyl starch (HES). The efficacy of hydroxyethyl starch with a 130 molecular weight and substitution degree of 0.4 (hydroxyethyl starch 130/0.4) was compared with human albumin for use in cardiopulmonary bypass surgery in American Society of Anesthesiologists’ grade I-II pediatric congenital heart disease patients. Efficacy was evaluated by comparing perioperative hemodynamic parameters, including plasma colloid osmotic pressure, renal function, blood loss, allogeneic blood volumes and plasma volume substitution. The hydroxyethyl starch group exhibited significantly higher preoperative colloid osmotic pressure (p0.05). Our results indicate that hydroxyethyl starch may be a viable alternative to human albumin in pediatric patients undergoing relatively simple cardiopulmonary bypass surgeries. Keywords cardiopulmonary bypass; plasma colloid osmotic pressure; colloid solution; pediatric; priming solution
Introduction Volume replacement is an essential consideration in cardiopulmonary bypass (CPB) patients who may experience hemodynamic instability due to improper intravascular volumes.1 Colloids in the primer solution are important for the maintenance of blood volume. The use of colloids in primer solutions is associated with cardiac output, which is associated with intravascular volumes, myocardial contractility and vascular resistance. A variety of crystalloid and colloid solutions are available to prime CPB circuits, including blood and its components (e.g., human albumin [HA] and fresh frozen plasma [FFP]), natural colloids (e.g., gelatins), synthetic colloids (e.g., dextrans, hydroxyethyl starch [HES]) and crystalloids (e.g., lactated Ringer’s solution).2 Because correct plasma volume expansion is essential during cardiac surgery, colloids are generally preferred over crystalloids due to their greater effectiveness in increasing blood volume and, as a result, cardiac output.3 In adults, solutions designed to maintain plasma colloid osmotic pressure (COP) and, thus, reduce fluid retention, are well
described;4 however, COP and fluid retention during CPB merit special consideration in pediatric patients due to the requirement for variable fluid volumes and overload potential due to insufficient urine capacity.5 Thus, there is a need for specialized investigation into appropriate CPB primers for pediatric patients. Currently, natural colloidal HA is the preferred CPB priming solution for pediatric patients during cardiac surDepartment of Extracorporeal Circulation, Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China Corresponding author: Xiaotong Hou Department of Extracorporeal Circulation Center for Cardiac Intensive Care Beijing An-Zhen Hospital of Capital Medical University Beijing 100024 China Email: [email protected]; [email protected]
Downloaded from prf.sagepub.com at DALHOUSIE UNIV on July 11, 2014
2
Perfusion
gery.6 Golab et al.6 suggested that HA priming better preserved plasma albumin concentrations within physiological ranges and stabilized colloid pressure in very young patients. Similarly, a 10-year review of pediatric perfusion practices by Cecere et al.7 demonstrated that HA maintained COP and formed a protective protein coating over the inner surfaces of extracorporeal devices, thereby, simulating the endothelial surface, delaying fibrinogen adsorption and preventing platelet surface activation and adhesion during CPB.7 Compared with crystalloids, HA provides good intraoperative COP while reducing the occurrence of high postoperative positive fluid balance and detrimental drops in postoperative blood platelet count in adults and children undergoing open heart surgery.8 However, the administration of HA has some disadvantages, including higher manufacturing costs.9 HES is a less costly synthetic colloid derived from amylopectin, a branched polysaccharide component of waxy maize, resembling glycogen.10 Numerous HES modifications, with various molecular weights (MW 70-450 kD) and degrees of substitution (DS 0.7, 0.62 and 0.5), have been approved for clinical use in different countries.2 Previously, the use of relatively large HES (mean MW 450 kD, DS 0.7, known as HES 450/0.7) was limited by hemostasis inhibition and potential renal failure.10 However, the relatively smaller HES specification, HES 130/0.4, has been demonstrated as a safe alternative to HA in adult patients.10 The safety and efficacy of HES 130/0.4 for use in children undergoing CPB has not been extensively evaluated. In this study, we assessed the efficacy of 6% HES 130/0.4 as a priming solution in pediatric CPB patients compared with conventional 3.3% HA.
Material and Methods Study design A total of 60 children undergoing a first open heart CPB surgery for congenital heart disease were included in a prospective study of HES versus conventional HA as CPB primer solutions. Patients were randomized using a computer-generated random number table and treated with either 6% HES 130/0.4 (Voluven®, Fresenius Kabi, Beijing, China) (HES group, n = 30) or conventional 3.3% HA (ZLB, Behring®, Marburg, Germany) (HA group, n = 30) as a priming solution during CPB surgeries. The study protocol was approved by the Anzhen Hospital Ethical Committee (Beijing, China). Written informed consent was provided by the parents or legal guardian of each patient.
Patients The patients included: (1) were aged from 3 months to 1.5 years at the time of enrollment; (2) exhibited an
American Society of Anesthesiologists (ASA) grade I-II classification risk; and (3) were diagnosed with congenital heart failure based on the Framingham Criteria for Congestive Heart Failure; conditions included ventricular septal, atrial septal or ventricular and atrial septal defects.11 Patients were excluded if they exhibited signs or symptoms of complications or conditions including infection, renal insufficiency or other organ failure.
CPB surgery Patients were anesthetized by an intravenous injection of a mixture of fentanyl (10ug/kg), midazolam (0.1mg/ kg) and pipecuronium (0.1mg/kg). Arterial and double venous cannulae were inserted into the radial artery and right internal jugular vein, respectively. Patients were subjected to routine monitoring of electrocardiogram, nasopharyngeal and rectal temperature and urinary volume. The CPB circuit was established with an integrated microporous membrane oxygenator (CAPIOX RX05; Terumo, Tokyo, Japan) and arterial filter (Terumo, Ningbo, China). For the HES group, the priming solution was prepared as: 250 ml of 6% HES 130/0.4, 50 ml of 5% NaHCO3 and 1 unit of a red blood cell suspension (about 150 ml, because red blood cell suspensions are calculated as units); if the total priming solution volume did not reach 450 ml, we added Multiple Electrolytes Injection (Baxter Healthcare Corp., Deerfield, IL, USA) to ensure a total volume of 450 ml. For the HA group, the priming solution was prepared as: 50 ml of 20% HA, 50 ml of 5% NaHCO3 and 1 unit of red blood cell suspension; we then added Multiple Electrolytes Injection (about 200 ml) to ensure a total volume of 450 ml. The CPB circuit (including the arterial filter and the circulation loop) was primed with 450 ml of priming solution. A variable volume of red blood cell suspension was added to ensure an hematocrit of >24% during the initiation of CPB. Transfusion therapy was standardized to established protocols. The targeted post-CPB hematocrit was above 27%. Conventional ultrafiltration was used during CPB and modified ultrafiltration was used after CPB to remove inflammatory mediators, reduce edema formation and improve organ function.
Specimen collection and assessments The surgical procedure and perioperative outcomes were recorded for each patient, along with clinical data (including age, weight and gender), patient recovery and COP (ONKOMETER BMT 923, BMT Messtechnik GmbH, Berlin, Germany), according to the manufacturer’s instructions, after the induction of anesthesia, 10 minutes after CPB initiation and after protamine treatment. Laboratory measurements, including hematocrit,
Downloaded from prf.sagepub.com at DALHOUSIE UNIV on July 11, 2014
3
Miao et al. Table 1. Demographic and clinical information. Characteristic
HES group (n = 30)
HA group (n = 30)
p-value
Gender (M/F) Age (day) Weight (kg) Diagnosis Ventricular septal defect Atrial septal defect Atrial and ventricular septal defect CPB time (min) ACC time (min) Ventilation time (hr) Intensive care unit stay (hr)
11/19 243±89 (90–450) 7.0±1.5 (3.6–10)
12/18 246±86 (122–450) 6.9±1.5 (5–10)
15 (50.0%) 10 (33.3%) 5 (16.7%) 61±15 (37–93) 42±21 (20–115) 17±10 (4–40) 35±19 (10–72)
17 (56.7%) 6 (20%) 7 (23.3%) 61±17 (35–97) 39±13 (17–70) 18±13 (3–58) 36±21 (10–106)
0.79 0.903 0.795 0.482 0.959 0.480 0.741 0.843
Note: Data are presented as mean ± SD (range) or %. The HA group was treated with 3.3% human albumin and the HES group was treated with 6% hydroxyethyl starch (HES 130/0.4). ACC: aortic cross-clamping; CPB: cardiopulmonary bypass.
platelet counts, glucose levels, lactic acid levels and serum creatinine levels were recorded 10 minutes after CPB initiation and 5 min post-CPB. Fluid administration, blood loss, volume of allogeneic blood products and renal function were measured during the operation and 6 hours postoperatively.
Statistical analysis All statistical analyses were performed using SPSS v.13.0 (SPSS, Inc., Chicago, IL, USA). Continuous data are presented as mean ± standard deviation (SD) and categorical data are presented as proportions. Continuous data were evaluated for normal distribution using the Kolmogorov-Smirnov test and normally distributed between-group data was compared by the unpaired Student’s t test. Differences within groups were evaluated by one-way analysis of variance (ANOVA). Posthoc analysis used Fisher’s least significant difference (LSD) test. A two-tailed p-value of less than 0.05 was considered statistically significant (p
http://prf.sagepub.com/
Comparison of low molecular weight hydroxyethyl starch and human albumin as priming solutions in children undergoing cardiac surgery Na Miao, Jing Yang, Zhongtao Du, Wei Liu, Hong Ni, Jialin Xing, Xiaofang Yang, Bo Xu and Xiaotong Hou Perfusion published online 21 March 2014 DOI: 10.1177/0267659114528267 The online version of this article can be found at: http://prf.sagepub.com/content/early/2014/03/21/0267659114528267
Published by: http://www.sagepublications.com
Additional services and information for Perfusion can be found at: Email Alerts: http://prf.sagepub.com/cgi/alerts Subscriptions: http://prf.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Mar 21, 2014 What is This?
Downloaded from prf.sagepub.com at DALHOUSIE UNIV on July 11, 2014
528267 research-article2014
PRF0010.1177/0267659114528267PerfusionMiao et al.
Original paper
Comparison of low molecular weight hydroxyethyl starch and human albumin as priming solutions in children undergoing cardiac surgery
Perfusion 1–7 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0267659114528267 prf.sagepub.com
Na Miao, Jing Yang, Zhongtao Du, Wei Liu, Hong Ni, Jialin Xing, Xiaofang Yang, Bo Xu and Xiaotong Hou
Abstract Human albumin is the conventional cardiopulmonary bypass circuit primer. However, it has high manufacturing costs. Crystalloid and colloid solutions have been developed as alternatives, including a new generation of non-ionic hydroxyethyl starch (HES). The efficacy of hydroxyethyl starch with a 130 molecular weight and substitution degree of 0.4 (hydroxyethyl starch 130/0.4) was compared with human albumin for use in cardiopulmonary bypass surgery in American Society of Anesthesiologists’ grade I-II pediatric congenital heart disease patients. Efficacy was evaluated by comparing perioperative hemodynamic parameters, including plasma colloid osmotic pressure, renal function, blood loss, allogeneic blood volumes and plasma volume substitution. The hydroxyethyl starch group exhibited significantly higher preoperative colloid osmotic pressure (p0.05). Our results indicate that hydroxyethyl starch may be a viable alternative to human albumin in pediatric patients undergoing relatively simple cardiopulmonary bypass surgeries. Keywords cardiopulmonary bypass; plasma colloid osmotic pressure; colloid solution; pediatric; priming solution
Introduction Volume replacement is an essential consideration in cardiopulmonary bypass (CPB) patients who may experience hemodynamic instability due to improper intravascular volumes.1 Colloids in the primer solution are important for the maintenance of blood volume. The use of colloids in primer solutions is associated with cardiac output, which is associated with intravascular volumes, myocardial contractility and vascular resistance. A variety of crystalloid and colloid solutions are available to prime CPB circuits, including blood and its components (e.g., human albumin [HA] and fresh frozen plasma [FFP]), natural colloids (e.g., gelatins), synthetic colloids (e.g., dextrans, hydroxyethyl starch [HES]) and crystalloids (e.g., lactated Ringer’s solution).2 Because correct plasma volume expansion is essential during cardiac surgery, colloids are generally preferred over crystalloids due to their greater effectiveness in increasing blood volume and, as a result, cardiac output.3 In adults, solutions designed to maintain plasma colloid osmotic pressure (COP) and, thus, reduce fluid retention, are well
described;4 however, COP and fluid retention during CPB merit special consideration in pediatric patients due to the requirement for variable fluid volumes and overload potential due to insufficient urine capacity.5 Thus, there is a need for specialized investigation into appropriate CPB primers for pediatric patients. Currently, natural colloidal HA is the preferred CPB priming solution for pediatric patients during cardiac surDepartment of Extracorporeal Circulation, Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China Corresponding author: Xiaotong Hou Department of Extracorporeal Circulation Center for Cardiac Intensive Care Beijing An-Zhen Hospital of Capital Medical University Beijing 100024 China Email: [email protected]; [email protected]
Downloaded from prf.sagepub.com at DALHOUSIE UNIV on July 11, 2014
2
Perfusion
gery.6 Golab et al.6 suggested that HA priming better preserved plasma albumin concentrations within physiological ranges and stabilized colloid pressure in very young patients. Similarly, a 10-year review of pediatric perfusion practices by Cecere et al.7 demonstrated that HA maintained COP and formed a protective protein coating over the inner surfaces of extracorporeal devices, thereby, simulating the endothelial surface, delaying fibrinogen adsorption and preventing platelet surface activation and adhesion during CPB.7 Compared with crystalloids, HA provides good intraoperative COP while reducing the occurrence of high postoperative positive fluid balance and detrimental drops in postoperative blood platelet count in adults and children undergoing open heart surgery.8 However, the administration of HA has some disadvantages, including higher manufacturing costs.9 HES is a less costly synthetic colloid derived from amylopectin, a branched polysaccharide component of waxy maize, resembling glycogen.10 Numerous HES modifications, with various molecular weights (MW 70-450 kD) and degrees of substitution (DS 0.7, 0.62 and 0.5), have been approved for clinical use in different countries.2 Previously, the use of relatively large HES (mean MW 450 kD, DS 0.7, known as HES 450/0.7) was limited by hemostasis inhibition and potential renal failure.10 However, the relatively smaller HES specification, HES 130/0.4, has been demonstrated as a safe alternative to HA in adult patients.10 The safety and efficacy of HES 130/0.4 for use in children undergoing CPB has not been extensively evaluated. In this study, we assessed the efficacy of 6% HES 130/0.4 as a priming solution in pediatric CPB patients compared with conventional 3.3% HA.
Material and Methods Study design A total of 60 children undergoing a first open heart CPB surgery for congenital heart disease were included in a prospective study of HES versus conventional HA as CPB primer solutions. Patients were randomized using a computer-generated random number table and treated with either 6% HES 130/0.4 (Voluven®, Fresenius Kabi, Beijing, China) (HES group, n = 30) or conventional 3.3% HA (ZLB, Behring®, Marburg, Germany) (HA group, n = 30) as a priming solution during CPB surgeries. The study protocol was approved by the Anzhen Hospital Ethical Committee (Beijing, China). Written informed consent was provided by the parents or legal guardian of each patient.
Patients The patients included: (1) were aged from 3 months to 1.5 years at the time of enrollment; (2) exhibited an
American Society of Anesthesiologists (ASA) grade I-II classification risk; and (3) were diagnosed with congenital heart failure based on the Framingham Criteria for Congestive Heart Failure; conditions included ventricular septal, atrial septal or ventricular and atrial septal defects.11 Patients were excluded if they exhibited signs or symptoms of complications or conditions including infection, renal insufficiency or other organ failure.
CPB surgery Patients were anesthetized by an intravenous injection of a mixture of fentanyl (10ug/kg), midazolam (0.1mg/ kg) and pipecuronium (0.1mg/kg). Arterial and double venous cannulae were inserted into the radial artery and right internal jugular vein, respectively. Patients were subjected to routine monitoring of electrocardiogram, nasopharyngeal and rectal temperature and urinary volume. The CPB circuit was established with an integrated microporous membrane oxygenator (CAPIOX RX05; Terumo, Tokyo, Japan) and arterial filter (Terumo, Ningbo, China). For the HES group, the priming solution was prepared as: 250 ml of 6% HES 130/0.4, 50 ml of 5% NaHCO3 and 1 unit of a red blood cell suspension (about 150 ml, because red blood cell suspensions are calculated as units); if the total priming solution volume did not reach 450 ml, we added Multiple Electrolytes Injection (Baxter Healthcare Corp., Deerfield, IL, USA) to ensure a total volume of 450 ml. For the HA group, the priming solution was prepared as: 50 ml of 20% HA, 50 ml of 5% NaHCO3 and 1 unit of red blood cell suspension; we then added Multiple Electrolytes Injection (about 200 ml) to ensure a total volume of 450 ml. The CPB circuit (including the arterial filter and the circulation loop) was primed with 450 ml of priming solution. A variable volume of red blood cell suspension was added to ensure an hematocrit of >24% during the initiation of CPB. Transfusion therapy was standardized to established protocols. The targeted post-CPB hematocrit was above 27%. Conventional ultrafiltration was used during CPB and modified ultrafiltration was used after CPB to remove inflammatory mediators, reduce edema formation and improve organ function.
Specimen collection and assessments The surgical procedure and perioperative outcomes were recorded for each patient, along with clinical data (including age, weight and gender), patient recovery and COP (ONKOMETER BMT 923, BMT Messtechnik GmbH, Berlin, Germany), according to the manufacturer’s instructions, after the induction of anesthesia, 10 minutes after CPB initiation and after protamine treatment. Laboratory measurements, including hematocrit,
Downloaded from prf.sagepub.com at DALHOUSIE UNIV on July 11, 2014
3
Miao et al. Table 1. Demographic and clinical information. Characteristic
HES group (n = 30)
HA group (n = 30)
p-value
Gender (M/F) Age (day) Weight (kg) Diagnosis Ventricular septal defect Atrial septal defect Atrial and ventricular septal defect CPB time (min) ACC time (min) Ventilation time (hr) Intensive care unit stay (hr)
11/19 243±89 (90–450) 7.0±1.5 (3.6–10)
12/18 246±86 (122–450) 6.9±1.5 (5–10)
15 (50.0%) 10 (33.3%) 5 (16.7%) 61±15 (37–93) 42±21 (20–115) 17±10 (4–40) 35±19 (10–72)
17 (56.7%) 6 (20%) 7 (23.3%) 61±17 (35–97) 39±13 (17–70) 18±13 (3–58) 36±21 (10–106)
0.79 0.903 0.795 0.482 0.959 0.480 0.741 0.843
Note: Data are presented as mean ± SD (range) or %. The HA group was treated with 3.3% human albumin and the HES group was treated with 6% hydroxyethyl starch (HES 130/0.4). ACC: aortic cross-clamping; CPB: cardiopulmonary bypass.
platelet counts, glucose levels, lactic acid levels and serum creatinine levels were recorded 10 minutes after CPB initiation and 5 min post-CPB. Fluid administration, blood loss, volume of allogeneic blood products and renal function were measured during the operation and 6 hours postoperatively.
Statistical analysis All statistical analyses were performed using SPSS v.13.0 (SPSS, Inc., Chicago, IL, USA). Continuous data are presented as mean ± standard deviation (SD) and categorical data are presented as proportions. Continuous data were evaluated for normal distribution using the Kolmogorov-Smirnov test and normally distributed between-group data was compared by the unpaired Student’s t test. Differences within groups were evaluated by one-way analysis of variance (ANOVA). Posthoc analysis used Fisher’s least significant difference (LSD) test. A two-tailed p-value of less than 0.05 was considered statistically significant (p
