1.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
;
Colloids
;
Crystalloid Solutions/therapeutic use*
;
Fluid Therapy
;
Glycocalyx
;
Humans
;
Hydroxyethyl Starch Derivatives
;
Isotonic Solutions
;
Microcirculation
;
Resuscitation
4.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
5.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
;
Fluid Therapy
;
Hemorrhage
;
Hydroxyethyl Starch Derivatives
;
therapeutic use
;
Resuscitation
;
Shock, Hemorrhagic
;
pathology
;
therapy
;
Spleen
;
diagnostic imaging
;
Tomography, X-Ray Computed
;
Ultrasonography
6.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
;
Blood Coagulation/drug effects
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Cardiac Surgical Procedures/*methods
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Cardiopulmonary Bypass/methods
;
Female
;
Humans
;
Hydroxyethyl Starch Derivatives/*therapeutic use
;
Male
;
Middle Aged
7.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
8.Alternatives to albumin administration in hepatocellular carcinoma patients undergoing hepatectomy: an open, randomized clinical trial of efficacy and safety.
Jian YANG ; Wen-Tao WANG ; Lü-Nan YAN ; Ming-Qing XU ; Jia-Yin YANG
Chinese Medical Journal 2011;124(10):1458-1464
BACKGROUNDThe value of artificial colloids in treating patients with liver disease is controversial. The effects of intravascular volume replacement regimens on liver function secondary to alteration of the postoperative inflammatory response are not known. In this study, we evaluated the effects of different volume replacement regimens in hepatocellular carcinoma patients undergoing hepatectomy to clarify whether albumin administration can be replaced by other volume replacement products.
METHODSNinety consecutive hepatocellular carcinoma patients scheduled for hepatectomy were prospectively randomized to receive 20% human albumin (HA), 6% hydroxyethyl starch (HES) or lactated Ringer's solution (LR) for postoperative volume replacement. Hemodynamic, liver function and inflammatory response parameters were recorded on postoperative days one, three, and five throughout the investigation period.
RESULTSSignificantly less volume was required in the HA and the HES groups. Although patients in all groups had similar baseline values, the plasma osmolality was significantly higher in the HA and HES groups. Total bilirubin (TB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) increased from baseline in all groups, and did not differ significantly between groups. C-reactive protein (CRP) was significantly lower in the HES group compared with the other groups.
CONCLUSIONSIn hepatocellular carcinoma patients undergoing hepatectomy, HA can be replaced by HES or LR in well selected patients. Hemodynamic stability, liver function, and postoperative clinical outcomes could be equivalently achieved in the HES group; also, HES may exert more favorable effects on the acute phase response.
Adolescent ; Adult ; Aged ; Albumins ; therapeutic use ; Carcinoma, Hepatocellular ; surgery ; Female ; Hemodynamics ; Hepatectomy ; methods ; Humans ; Hydroxyethyl Starch Derivatives ; therapeutic use ; Isotonic Solutions ; therapeutic use ; Liver Neoplasms ; surgery ; Male ; Middle Aged ; Young Adult
9.Protective effects of hydroxyethyl starch 130/0.4 against myocardial ischemia/reperfusion injury in rats.
Hai-Jing SUN ; Hao LI ; Zui ZOU ; Xue-Yin SHI
Chinese Medical Journal 2011;124(2):291-297
BACKGROUNDThe effects of hydroxyethyl starch 130/0.4 (HES130/0.4) on myocardial ischemia/reperfusion (I/R) injury and its mechanism are uncertain. The aim of this study was to investigate the protective effects of HES 130/0.4 on myocardial I/R injury.
METHODSForty-eight Sprague-Dawley rats were assigned to sham-operation group (S group), ischemia-reperfusion group (I/R group), albumin-I/R group (A-I/R group) and HES130/0.4-I/R group (H-I/R group). The fluids were administered at 25 minutes after ischemia. H-I/R group was given 7.5 ml/kg of HES 130/0.4; I/R group and A-I/R group received the same volume of normal saline and 5% albumin, respectively. The rats in S group were sham operated and received the same fluid as I/R group. After 30 minutes of ischemia and 3 hours of reperfusion, blood samples were taken for cytokines assay, myocardium was excised for detection of NF-κB activity and myocardial infarction areas were taken for immunohistochemical analysis.
RESULTSHemodynamic parameters of H-I/R group were better than I/R and A-I/R groups at all designated time points. The results of 2,3,5-triphenyl-tetrazolium (TTC) and HE staining were better in the H-I/R group. Myeloperoxidase (MPO), NF-κB activity and concentrations of TNF-α, IL-1β were elevated markedly in I/R groups. HES130/0.4 lessened the release of TNF-α and IL-1β consistent with the reduction of MPO activity, and HES 130/0.4 inhibited the activity of NF-κB in H-I/R group. The number of apoptotic cells in the H-I/R group was also significantly reduced compared with I/R and A-I/R group
CONCLUSIONHES130/0.4 has a protective effect on I/R injured myocardium, probably by inhibiting NF-κB activity, reducing the release of pro-inflammatory cytokines and interfering with the apoptosis of cardiomyocytes.
Animals ; Hemodynamics ; drug effects ; Hydroxyethyl Starch Derivatives ; therapeutic use ; Interleukin-1beta ; metabolism ; Male ; NF-kappa B ; metabolism ; Peroxidase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; pathology ; prevention & control ; Tumor Necrosis Factor-alpha ; metabolism
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

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