3.Sources of Heterogeneity in Trials Reporting Hydroxyethyl Starch 130/0.4 or 0.42 Associated Excess Mortality in Septic Patients: A Systematic Review and Meta-regression.
Peng-Lin MA ; Xiao-Xia PENG ; Bin DU ; Xiao-Lan HU ; Yi-Chun GONG ; Yu WANG ; Xiu-Ming XI
Chinese Medical Journal 2015;128(17):2374-2382
BACKGROUNDThis meta-analysis was to determine the association of the cumulative dose of 130/0.4 or 0.42 (hydroxyethyl starch [HES] 130/0.4*) or delta daily fluid balance (i.e., daily fluid balance in HES group over or below control group) with the heterogeneity of risk ratio (RR) for mortality in randomized control trials (RCTs).
METHODSThree databases (PubMed, EMBASE, Cochrane) were searched to identify prospective RCTs reporting mortality in adult patients with sepsis to compare HES130/0.4* with crystalloids or albumin. Meta-analysis was performed using random effects. Sensitivity and meta-regression analyses were used to examine the heterogeneity sources of RR for mortality.
RESULTSA total number of 4408 patients from 11 RCTs were included. The pooled RR showed no significant difference for overall mortality in patients with administration of HES130/0.4* compared with treatment of control fluids (RR: 1.02, 95% confidence interval: 0.90-1.17; P = 0.73). Heterogeneity was moderate across recruited trials (I2 = 34%, P = 0.13). But, a significant variation was demonstrated in subgroup with crystalloids as control fluids (I2 = 42%, P < 0.1). Sensitivity analysis revealed that trials with high risk of bias did not significantly impact the pooled estimates for mortality. Meta-regression analysis also did not determine a dose-effect relationship of HES130/0.4* with mortality (P = 0.298), but suggested daily delta fluid balance being likely associated with mortality in septic patients receiving HES130/130/0.4* (P = 0.079).
CONCLUSIONSInappropriate daily positive fluid balance was likely an important source of heterogeneity in these trials reporting HES130/0.4* associated with excess mortality in septic patients.
Humans ; Hydroxyethyl Starch Derivatives ; therapeutic use ; Randomized Controlled Trials as Topic ; Sepsis ; mortality ; therapy
4.Evaluation of effectiveness and safety of a new hydroxyethyl starch used in resuscitation of burn shock.
Jiong CHEN ; Chun-mao HAN ; Shi-chun XIA ; Zhi-jian TANG ; Shi-jie SU
Chinese Journal of Burns 2006;22(5):333-336
OBJECTIVETo evaluate the effectiveness and safety of hydroxyethyl starch (HES 130/ 0.4, 60 g/L) in resuscitation during shock stage of burns.
METHODSSixty-six burn patients who were admitted to hospital within 2 hours after burn injury requiring fluid resuscitation were enrolled into this study, and they were randomized into HES( n = 33, with HES as a component of fluid resuscitation) and plasma (P, n = 33, with plasma as a component of fluid resuscitation) groups. HES or plasma was given as colloid within 48 postburn hours (PBH), and only albumin [( 111 +/- 4) , ( 105 +/- 5 ) g for each group] were given to the patients during 3 to 7 postburn days (PBD). Heart rate, blood pressure, central venous pressure (CVP) , urine output per hour were measured, gain/loss of body fluid during the first and second 24 PBH were recorded, serum total protein, albumin, hemoglobin( Hb) , prothrombin time (PT) , fibrinogen; platelet ( PLT) , as well as liver and renal function, allergy and bleeding tendency were determined and observed at corresponding time-points.
RESULTSThere were no obvious differences in heart rate, blood pressure, CVP and urine output per hour within 24 PBH between the two groups (P > 0.05). Also there was no difference in gain/loss of body fluid during the first and second 24 PBH. The content of hemoglobin on 1 ,3, 7,14 PBD ,and the PT, the content of fibrinogen, the number of PLT on 1,3,14 PBD also exhibited no difference between the two groups (P > 0.05). The serum contents of total protein and albumin in HES group were [(31 +/- 3) g/L, (30 +/- 3)g/L ] on 1 PBD, and [(20.4 +/- 3.6) g/L, (18.4 +/-2.3) g/L] on 3 PBD, which were obviously lower than those in P group [(45 +/- 4) g/L, (39 +/- 3) g/L on 1 PBD, and 1 (24.5 +/- 4.3) g/L, (21.3 +/- 3.9) g/L) on 3 PBD, (P <0. 01). Though the serum content of albumin on 7 PBD was similar in the two groups (P > 0.05), the serum total protein in HES group (40 +/- 4) g/L was markedly lower than that in P group [(45 +/- 4) g/L, P < 0.01] . Within 7 PBD, no abnormal bleeding was found in the two groups, and the liver function and renal function were similar. There were 4 cases showing allergic reaction in plasma group while none in HES group.
CONCLUSIONNew type of HES can partially substitute plasma and be used in fluid resuscitation for burn patients. However, plasma protein replenishment should still be emphasized.
Adult ; Burns ; therapy ; Female ; Humans ; Hydroxyethyl Starch Derivatives ; therapeutic use ; Male ; Middle Aged ; Resuscitation ; methods ; Shock ; therapy
5.Resuscitation fluids as drugs: targeting the endothelial glycocalyx.
Guangjian WANG ; Hongmin ZHANG ; Dawei LIU ; Xiaoting WANG
Chinese Medical Journal 2022;135(2):137-144
Fluid resuscitation is an essential intervention in critically ill patients, and its ultimate goal is to restore tissue perfusion. Critical illnesses are often accompanied by glycocalyx degradation caused by inflammatory reactions, hypoperfusion, shock, and so forth, leading to disturbed microcirculatory perfusion and organ dysfunction. Therefore, maintaining or even restoring the glycocalyx integrity may be of high priority in the therapeutic strategy. Like drugs, however, different resuscitation fluids may have beneficial or harmful effects on the integrity of the glycocalyx. The purpose of this article is to review the effects of different resuscitation fluids on the glycocalyx. Many animal studies have shown that normal saline might be associated with glycocalyx degradation, but clinical studies have not confirmed this finding. Hydroxyethyl starch (HES), rather than other synthetic colloids, may restore the glycocalyx. However, the use of HES also leads to serious adverse events such as acute kidney injury and bleeding tendencies. Some studies have suggested that albumin may restore the glycocalyx, whereas others have suggested that balanced crystalloids might aggravate glycocalyx degradation. Notably, most studies did not correct the effects of the infusion rate or fluid volume; therefore, the results of using balanced crystalloids remain unclear. Moreover, mainly animal studies have suggested that plasma may protect and restore glycocalyx integrity, and this still requires confirmation by high-quality clinical studies.
Animals
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Colloids
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Crystalloid Solutions/therapeutic use*
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Fluid Therapy
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Glycocalyx
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Humans
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Hydroxyethyl Starch Derivatives
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Isotonic Solutions
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Microcirculation
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Resuscitation
6.Effects of hypertonic sodium chloride hydroxyethyl starch 40 on brain histopathology in rats with whole body hyperthermia.
Lian-zhong CAI ; Li-fang ZHAN ; You-tan LIU ; Jin-song CHEN ; Shao-nong HUANG ; Miao-ning GU ; Jing TANG ; Tao TAO
Journal of Southern Medical University 2011;31(12):2067-2071
OBJECTIVETo investigate the effects of hypertonic sodium chloride hydroxyethyl starch 40 (HSH) on brain edema and morphological changes during whole body hyperthermia (WBH) in rats.
METHODSSixty adult male SD rats were randomized into control group, WBH group without fluid infusion (group HT), WBH group with Ringer's infusion (group RL), WBH group with HAES + Ringer's infusion (group HRL) and WBH group with HSH infusion (group HSH). WBH was induced by exposure to 36 degrees celsius; for 3 h to achieve a rectal temperature of 41-42 degrees celsius;, and the corresponding fluids were administered intravenously within 30 min at the beginning of WBH. The control rats were housed at a controlled room temperature (22∓1) degrees celsius; for 4 h. After cooling at room temperature for 1 h, the rats were sacrificed and brain water content and morphological changes were evaluated.
RESULTSCompared with the control group, all the WBH groups had significantly increased brain water content (P<0.05 or 0.01), but group HSH showed a significantly lower brain water content than group HT (P<0.05). The rats in groups HT, RL and HRL showed serious to moderate structural changes of the brain tissue and nerve cells, but HSH group had only mild pathologies.
CONCLUSIONHSH can reduce brain edema and ameliorate the damages to brain cells in rats exposed to WBH.
Animals ; Brain ; pathology ; Brain Edema ; pathology ; prevention & control ; Hydroxyethyl Starch Derivatives ; therapeutic use ; Hyperthermia, Induced ; adverse effects ; Male ; Rats ; Rats, Sprague-Dawley ; Saline Solution, Hypertonic ; therapeutic use
7.Effect of 6% Hydroxyethyl Starch 130/0.4 as a Priming Solution on Coagulation and Inflammation Following Complex Heart Surgery.
Jang Eun CHO ; Jae Kwang SHIM ; Jong Won SONG ; Hye Won LEE ; Dong Hwan KIM ; Young Lan KWAK
Yonsei Medical Journal 2014;55(3):625-634
PURPOSE: Prolonged duration of cardiopulmonary bypass aggravates the degree of inflammation and coagulopathy. We investigated the influence of 6% hydroxyethyl starch (HES) 130/0.4 on coagulation and inflammation compared with albumin when used for both cardiopulmonary bypass priming and perioperative fluid therapy in patients undergoing complex valvular heart surgery. MATERIALS AND METHODS: Fifty four patients were randomly allocated into albumin-HES, albumin-nonHES, and HES-HES groups. The cardiopulmonary bypass circuit was primed with 5% albumin in the albumin-HES and albumin-nonHES group, and with HES in the HES-HES group. As perioperative fluid, only plasmalyte was used in the albumin-nonHES group whereas HES was used up to 20 mL/kg in the albumin-HES and albumin-HES group. Serial assessments of coagulation profiles using the rotational thromboelastometry and inflammatory markers (tissue necrosis factor-alpha, interleukin-6, and interleukin-8) were performed. RESULTS: Patients' characteristics and the duration of cardiopulmonary bypass (albumin-HES; 137+/-34 min, HES-HES; 136+/-47 min, albumin-nonHES; 132+/-39 min) were all similar among the groups. Postoperative coagulation profiles demonstrated sporadic increases in clot formation time and coagulation time, without any differences in the actual amount of perioperative bleeding and transfusion requirements among the groups. Also, inflammatory markers showed significant activation after cardiopulmonary bypass without any differences among the groups. CONCLUSION: Even in the presence of prolonged duration of cardiopulmonary bypass, HES seemed to yield similar influence on the ensuing coagulopathy and inflammatory response when used for priming and perioperative fluid therapy following complex valvular heart surgery compared with conventional fluid regimen including albumin and plasmalyte.
Aged
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Blood Coagulation/drug effects
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Cardiac Surgical Procedures/*methods
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Cardiopulmonary Bypass/methods
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Female
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Humans
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Hydroxyethyl Starch Derivatives/*therapeutic use
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Male
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Middle Aged
8.Effect of volume replacement with hydroxyethyl starch solution on splanchnic oxygenation in patients undergoing cytoreductive surgery for ovarian cancer.
Xiangyang GUO ; Zhonghuang XU ; Hongzhi REN ; Ailun LUO ; Yuguang HUANG ; Tiehu YE
Chinese Medical Journal 2003;116(7):996-1000
OBJECTIVETo investigate the effectiveness of using a medium molecular weight hydroxyethyl starch solution (HES) administered as a replacement for estimated blood loss (EBL) during cytoreductive surgery for ovarian cancer on splanchnic oxygenation.
METHODSForty-two patients undergoing cytoreductive surgery for ovarian cancer were enrolled in this prospective randomized study. As soon as the EBL exceeded 10% but was less than 20% of the estimated blood volume, the patients were randomly assigned to receive either a volume of lactated Ringer's solution (LRS) equal to three times the EBL (LRS group, n = 22) or a volume of 6% HES equal to the EBL (HES group, n = 20). Tissue oxygenation was assessed indirectly by measuring tonometric parameters, including the difference between gastric intramucosal PsCO(2) and arterial PaCO(2) (Ps-a CO(2) gap), gastric intramucosal pH (pHi) and arterial lactate acid concentration at 30 min after induction of anesthesia (baseline value), 1 hour and 2 hours after skin incision, and at the end of surgery.
RESULTSAt the end of surgery,the Ps-a CO(2) gap in the HES group (8.7 +/- 1.6 mmHg) was significantly lower than that of the LRS group (18.74 +/- 4.4 mmHg, P < 0.01), while the pHi (7.30 +/- 0.05 mmHg) in the HES group was significantly higher than that of the LRS group (7.21 +/- 0.07 mmHg, P < 0.01). There was no significant difference between the two groups in terms of arterial lactate acid concentration.
CONCLUSIONIn patients undergoing major surgery with relatively large blood losses, volume resuscitation with medium molecular weight hydroxyethyl starch solution may improve splanchnic blood flow and tissue oxygenation.
Blood Loss, Surgical ; Female ; Humans ; Hydroxyethyl Starch Derivatives ; therapeutic use ; Middle Aged ; Ovarian Neoplasms ; surgery ; Oxygen ; metabolism ; Prospective Studies ; Splanchnic Circulation
9.Contrast-enhanced ultrasound for the signature analysis of splenic trauma in a canine model during hemorrhagic shock and resuscitation.
Qian LIN ; Faqin LÜ ; Yukun LUO ; Qing SONG ; Yihua SU ; Jie TANG
Journal of Central South University(Medical Sciences) 2015;40(1):59-66
OBJECTIVE:
To conduct signature analysis for splenic trauma in canines during hemorrhagic shock and resuscitation by contrast enhanced ultrasonography (CEUS).
METHODS:
Forty grade III-IV traumatic splenic lesions were established in 15 mongrel dogs. Hemorrhagic shock was induced in these animals by using the modified Wiggers's method. Animals in shock were then resuscitated with 6% hydroxyethyl starch. The features of splenic trauma during hemorrhagic shock or resuscitation were assessed by CEUS, which were compared with the data collected by contrast-enhanced computed tomography (CECT). Acoustic quantification of CEUS was performed to assess splenic blood perfusion in different stages.
RESULTS:
There was no significant difference in detection rate between CEUS and CECT during hemorrhagic shock and resuscitation. Before hemorrhagic shock, there were 40 traumatic bleeding lesions and 85% of them were revealed by CEUS (34/40). With the progress in shock, CEUS revealed that the numbers of tiny branches of splenic arteries were decreased, which became thinner with no active bleeding. After fluid resuscitation, rebleeding was occurred in 30 traumatic lesions, and 28 (93.3%) of them were captured by CEUS. CEUS could also visualize the changes in splenic perfusion in different stages. During the shock, the arrival time (AT), time to peak intensity (TTP), peak intensity (PI) were significantly lower and the washout time (WT) were significantly higher than those at other stages (P<0.01).
CONCLUSION
CEUS not only can dynamically monitor the changes in spleen traumatic hemorrhage and recurrent hemorrhage, but also can quantitatively study the changes in spleen blood perfusion in different stages.
Animals
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Contrast Media
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Disease Models, Animal
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Dogs
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Fluid Therapy
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Hemorrhage
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Hydroxyethyl Starch Derivatives
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therapeutic use
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Resuscitation
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Shock, Hemorrhagic
;
pathology
;
therapy
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Spleen
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diagnostic imaging
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Tomography, X-Ray Computed
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Ultrasonography
10.Effects of the novel 6% hydroxyethyl starch 130/0.4 on renal function of recipients in living-related kidney transplantation.
Yan WU ; An-Shi WU ; Jun WANG ; Ming TIAN ; Xin-Yuan JIA ; Yan RUI ; Yun YUE
Chinese Medical Journal 2010;123(21):3079-3083
BACKGROUNDThe optimal colloid for use during kidney transplantation is not clear. Patients undergoing living-related kidney transplantation (LRKT) were used to compare the protective effects of 6% hydroxyethyl starch 130/0.4 (HES 130/0.4) and 4% succinylated gelatine, as donor kidney procurement, ischemia time and surgical conditions are comparable. Stroke volume variation (SVV) was used to monitor intravascular volume to avoid renal allograft hypoperfusion.
METHODSEighty patients undergoing LRKT were divided into two groups: group H received 6% HES 130/0.4 and group G received 4% succinylated gelatine. All donors and recipients received 15 - 25 ml/kg of the relevant colloid during surgery. Arterial blood pressure (ABP), heart rate (HR), central venous pressure (CVP), SVV and cardiac index (CI), electrocardiography (ECG) and SpO2 were monitored continuously. SVV was kept between 6% - 13% and mean arterial pressure at 100 - 130 mmHg. Samples of venous blood and urine were obtained 30 minutes after unclamping and on the mornings of post-operative days (POD) 1 - 4 to measure serum and urine β2-microglobulin, urine α1-microglobulin, microalbumin and N-acetyl-β-D-glucosaminidase. Blood urea nitrogen (BUN) and creatine were determined pre-operation (t(0)), 3 hours after surgery (t(1)) and on PODs 1 (t(2)), 2 (t(3)), 4 (t(4)), 7 (t(5)) and 10 (t(6)). Urine output was recorded at t(1), t(2), t(5), t(6).
RESULTSAge, body weight, body surface area (BSA), operation time, urine output and the colloid volume infused were comparable between the groups and hemodynamics were stable during surgery. BUN, serum creatine, serum β2-microglobulin and urine β2-microglobulin decreased significantly after surgery in both groups relative to the baseline. BUN decreased significantly in group H compared with group G at t(1), t(2) and t(4). Urine microalbumin decreased significantly in group H on POD 4 compared with group G. Urine α1-microglobulin was not significantly different between the two groups.
CONCLUSIONBoth colloids can be safely used for LRKT, but HES130/0.4 was associated with a more rapid recovery of renal function.
Adolescent ; Adult ; Aged ; Female ; Humans ; Hydroxyethyl Starch Derivatives ; therapeutic use ; Kidney ; drug effects ; Kidney Function Tests ; Kidney Transplantation ; methods ; Male ; Middle Aged ; Young Adult