Hydroxyethyl Starch for Fluid Management in Patients Undergoing Major Abdominal Surgery: A Systematic Review With Meta-analysis and Trial Sequential Analysis.

BACKGROUND: In critically ill patients, warnings about a risk of death and acute kidney injury (AKI) with hydroxyethyl starch (HES) solutions have been raised. However, HES solutions may yet have a role to play in major abdominal surgery. This meta-analysis and trial sequential analysis (TSA) aimed to investigate the effect of HES intravascular volume replacement on the risk of AKI, intraoperative blood transfusion, and postoperative intra-abdominal complications compared to crystalloid intravascular volume replacement. METHODS: In this meta-analysis and TSA, we searched for randomized controlled trials (RCTs) comparing intraoperative HES intravascular volume replacement to crystalloid intravascular volume replacement in adult patients undergoing major abdominal surgery. Primary outcome was 30-day AKI, defined as a binary outcome according to Kidney Disease Improving Global Outcomes (KDIGO) criteria, combining stages 1, 2, and 3 into an AKI category versus no AKI category (stage 0). Secondary outcomes included rates of intraoperative blood transfusion and postoperative intra-abdominal complications. We used random effects models to calculate summary estimates. We used relative risk (RR) as summary measure for dichotomous outcomes, with corresponding 95% confidence intervals (CIs) for the primary outcome (P value <.05 was considered statistically significant) and 99% CI after Bonferroni correction for the secondary outcomes (P value <.01 was considered statistically significant). RESULTS: Seven RCTs including 2398 patients were included. HES intravascular volume replacement was not associated with an increased risk of 30-day AKI (RR = 1.22, 95% CI, 0.94-1.59; P = .13), when compared to crystalloid intravascular volume replacement. According to TSA, this analysis was underpowered. HES intravascular volume replacement was associated with higher rates of blood transfusion (RR = 1.57 99% CI, 1.10-2.25; P = .001), and similar rates of postoperative intra-abdominal complications (RR = 0.76 99% CI, 0.57-1.02; P = .02). CONCLUSIONS: In this meta-analysis to focus on HES intravascular volume replacement in major abdominal surgery, HES intravascular volume replacement was not associated with a higher risk of 30-day AKI when compared to crystalloid intravascular volume replacement. However, CI and TSA do not exclude harmful effects of HES intravascular volume replacement on the renal function.

Does a balanced colloid decrease perioperative blood loss in paediatric cardiac surgery: A double-blinded randomized controlled trial?

BACKGROUND: Unbalanced fluid solutions cause metabolic acidosis and could be associated with impaired coagulation and increased blood loss. OBJECTIVE: To investigate whether the use of a balanced colloid compared with a saline colloid for peri-operative fluid therapy in children undergoing cardiac surgery is associated with decreased blood loss and exposure to blood products. DESIGN: Double-blinded randomised controlled trial. SETTING: Tertiary children's hospital from 2013 to 2016. PATIENTS: Children older than 29 days and younger than 3 years admitted for cardiac surgery with cardiopulmonary bypass (CPB). Exclusion criteria were emergency cardiac surgery, moribund (American Society of Anesthesiologists 5), Jehovah's witnesses, coagulopathy, renal failure, liver injury, intracranial haemorrhage and electrolyte disturbances. From the 128 patients eligible, 88 were included in the study. INTERVENTION: Random assignment of patients to either a saline colloid (6% hydroxyethyl starch 130/0.4 in 0.9% NaCl) or a balanced-electrolyte colloid (6% hydroxyethyl starch 130/0.4 in an isotonic solution) for CPB priming and intra- and postoperative fluid therapy during the first postoperative 48 h. MAIN OUTCOME MEASURE: The primary outcome measure was calculated blood loss until the third postoperative day (POD3). RESULTS: A total of 44 patients were included in each study arm. Calculated blood loss at POD3 was not significantly different between the groups (saline colloid 19.9 [IQR 13.8 to 26.1] ml kg-1 versus balanced colloid 15.9 [IQR 9.0 to 25.3 ml kg-1], P = 0.409). Secondary outcomes related to bleeding, exposure to blood products and coagulation were not different between groups. There was also no difference in length of mechanical ventilation, intensive care and hospital length of stay between groups. CONCLUSION: The use of a balanced colloid for peri-operative fluid therapy compared with a saline one is not associated with decreased blood loss or exposure to blood products. TRIAL REGISTRATION: EudraCT identifier: 2012-006034-17 and ClinicalTrial.gov identifier: NCT02584868.

Complex effects of continuous vasopressor infusion on fluid responsiveness during liver resection: A randomised controlled trial.

BACKGROUND: Fluid responsiveness is an important factor to consider for fluid volume loading during major surgery. The effect of continuous vasopressor infusion on fluid responsiveness during prolonged major surgery is a concern. OBJECTIVE: We hypothesised that continuous vasopressor infusion during major surgery might not exert significant effects on changes in stroke volume variation (SVV) following fluid bolus infusion, and thereby on fluid responsiveness. DESIGN: Randomised controlled trial. SETTING: University hospital from April 2014 to August 2016. PATIENTS: Patients undergoing liver resection who were randomised to receive continuous intravenous infusion of phenylephrine (P group), norepinephrine (N group), or no vasopressor (C group) (n=17/group). Exclusion criteria were cardiac arrhythmia and severe cardiac, pulmonary or renal dysfunction. INTERVENTION: Patients received 4 ml kg fluid boluses of 6% hydroxyethyl starch solution when SVV was at least 12%. Vasopressors were administered continuously to maintain the systemic vascular resistance index at more than 1900 dyn s cm m. MAIN OUTCOME MEASURES: Cardiac index and SVV were measured using the FloTrac/Vigileo system (Version 4.00). The number of fluid boluses with fluid responsiveness (i.e. >15% increase in cardiac index) was compared between groups using multilevel logistic regression analysis. RESULTS: Numbers of fluid responsive boluses in the C, P and N groups were 12 (14%), 22 (34%) and 19 (27%), respectively. Odds ratios on fluid responsiveness for phenylephrine and norepinephrine compared with the control were 3.65 (97.5% confidence interval, 1.15 to 11.6; P = 0.012) and 2.56 (97.5% confidence interval, 0.82 to 8.00; P = 0.064), respectively. Decreases in SVV after fluid bolus infusion for the P and N groups were comparable with the C group (P = 0.23 and 0.53, respectively). CONCLUSION: Continuous administration of phenylephrine increased fluid responsiveness during liver resection, suggesting complex effects of continuous vasopressor infusion involving changes in cardiac preload and afterload. TRIAL REGISTRATION: UMIN000011024.

Safety of gelatin solutions for the priming of cardiopulmonary bypass in cardiac surgery: a systematic review and meta-analysis.

This systematic review and meta-analysis was conducted to evaluate the safety of gelatin versus hydroxyethyl starches (HES) and crystalloids when used for cardiopulmonary bypass (CPB)-priming in cardiac surgery. MEDLINE (Pubmed), Embase and CENTRAL were searched. We included only randomized, controlled trials comparing CPB-priming with gelatin with either crystalloids or HES-solutions of the newest generation. The primary endpoint was the blood loss during the first 24 hours. Secondary outcomes included perioperative transfusion requirements, postoperative kidney function, postoperative ventilation times and length of stay on the intensive care unit. Sixteen studies were identified, of which only ten met the inclusion criteria, representing a total of 824 adult patients: 4 studies compared gelatin with crystalloid, and 6 studies gelatin with HES priming. Only 2 of the studies comparing HES and gelatin reported postoperative blood loss after 24 hours. No significant difference in postoperative blood loss was found when results of both studies were pooled (SMD -0.12; 95% CI: -0.49, 0.25; P=0.52). Likewise, the pooled results of 3 studies comparing gelatin and crystalloids as a priming solution could not demonstrate significant differences in postoperative bleeding after 24 hours (SMD -0.07; 95% CI: -0.40, 0.26; P=0.68). No differences regarding any of the secondary outcomes could be identified. This systematic review suggests gelatins to have a safety profile which is non-inferior to modern-generation tetrastarches or crystalloids. However, the grade of evidence is rated low owing to the poor methodological quality of the included studies, due to inconsistent outcome reporting and lack of uniform endpoint definitions.

Hydroxyethyl starch 130/0.4 versus crystalloid co-loading during general anesthesia induction: a randomized controlled trial.

PURPOSE: Hypotension and decreased cardiac output (CO) are common adverse effects during anesthesia induction depending on the patient's pre-anesthetic cardiac condition. The aim of this study was to assess the ability of hydroxyethyl starch (HES) 130/0.4 to prevent hypotension and decreased CO during the induction of general anesthesia. METHODS: Ninety patients undergoing laparoscopic surgery were randomly divided into a HES group and a crystalloid group. Following the insertion of an intravenous line, fluid was administered to each patient at a rate of 25 ml/min using either crystalloid or HES 130/0.4. Five minutes after the initiation of fluid loading, anesthesia was induced using propofol (1.5 mg/kg), rocuronium (0.9 mg/kg), and remifentanil (0.3 mcg/kg/min). Tracheal intubation was performed 5 min after the induction of anesthesia. Following tracheal intubation, general anesthesia was maintained using remifentanil and sevoflurane. Non-invasive blood pressure (BP) level was measured at 1-min intervals and CO was measured continuously using electrical cardiometry from the start of fluid loading until 5 min after tracheal intubation. RESULTS: The number of patients with hypotension (systolic BP < 90 mmHg or 80% of baseline) was significantly lower in the HES group (p < 0.001) than in the crystalloid group. Patients in the HES group showed smaller CO decreases than did patients in the crystalloid group (p < 0.001). The Kaplan-Meier method showed a lower incidence and significantly slower onset of hypotension in the HES group (p = 0.009). Multivariate logistic regression models indicated that the use of HES is an independent factor for the prevention of both hypotension and decreased CO (below 85% of baseline; p < 0.005 for both). CONCLUSIONS: Co-loading using HES 130/0.4 prevented hypotension and decreased CO during general anesthesia induction.

Rapid Infusion of Hydroxyethyl Starch 70/0.5 but not Acetate Ringer's Solution Decreases the Plasma Concentration of Propofol during Target-controlled Infusion.

BACKGROUND: Rapid fluid infusion resulting in increased hepatic blood flow may decrease the propofol plasma concentration (Cp) because propofol is a high hepatic extraction drug. The authors investigated the effects of rapid colloid and crystalloid infusions on the propofol Cp during target-controlled infusion. METHODS: Thirty-six patients were randomly assigned to 1 of 3 interventions (12 patients per group). At least 30 min after the start of propofol infusion, patients received either a 6% hydroxyethyl starch (HES) solution at 24 ml·kg·h or acetated Ringer's solution at 24 or 2 ml·kg·h during the first 20 min. In all groups, acetated Ringer's solution was infused at 2 ml·kg·h during the next 20 min. The propofol Cp was measured every 2.5 min as the primary outcome. Cardiac output, blood volume, and indocyanine green disappearance rate were determined using a pulse dye densitogram analyzer before and after the start of fluid administration. Effective hepatic blood flow was calculated as the blood volume multiplied by the indocyanine green disappearance rate. RESULTS: The rapid HES infusion significantly decreased the propofol Cp by 22 to 37%, compared to the Cp at 0 min, whereas the rapid or maintenance infusion of acetate Ringer's solution did not decrease the propofol Cp. Rapid HES infusion, but not acetate Ringer's solution infusion, increased the effective hepatic blood flow. CONCLUSIONS: Rapid HES infusion increased the effective hepatic blood flow, resulting in a decreased propofol Cp during target-controlled infusion. Rapid HES infusion should be used cautiously as it may decrease the depth of anesthesia.

The effect of colloid preload versus prophylactic ephedrine administration on QTc intervals during cesarean delivery: A randomized controlled study.

AIM: We aimed to investigate the effect of colloid infusion immediately before the spinal anesthesia, and the prophylactic intravenous (IV) infusion of ephedrine after injection of intrathecal bupivacaine on hemodynamic parameters, QT, The QT interval corrected for heart rate (QTc), and dispersion of QTc (QTcDisp) intervals in women undergoing the elective cesarean section. MATERIALS AND METHODS: Sixty women scheduled for elective cesarean delivery with spinal anesthesia were allocated randomly to receive either IV fluid preloading with 0.5 L of 6% w/v hydroxyethyl starch solution immediately before the spinal anesthesia (colloid group, n = 30) or prophylactic IV infusion of 15 mg ephedrine (diluted with 10 ml saline, n = 30) over 1-min period after the injection of intrathecal bupivacaine (ephedrine group). Electrocardiography (ECG) tracings were recorded before anesthesia procedure at baseline (T0), 5 min (T1), 10 min (T2), 30 min (T3), 60 min (T4), and 120 min (T5) after the spinal anesthesia. Systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), heart rate (HR), and peripheral oxygen saturation (SpO2) values were also recorded at the same time intervals. RESULTS: There were no significant differences between groups with respect to MAP, HR, SpO2, QT, and QTc intervals at any time points (P > 0.05). When compared with the colloid group, the QTcDisp interval at T1was significantly longer in the ephedrine group (P < 0.05). CONCLUSION: Both methods have similar effects on the ECG and hemodynamic parameters during cesarean section. So, both methods may be used in patients undergoing elective cesarean delivery under spinal anesthesia.

[Case in which massive hydroxyethylated starch (HES) infusion was useful for massive hemorrhage in spite of progressive hemodilution].

A 72-year-old man with no internal complication underwent total prostatectomy. During operation, massive hemorrhage occurred. Because of delay in transfusion, hemodilution progressed until minimum hemoglobin concentration of 1.6 g x dl(-1): minimum hematocrit of 4.8%. In spite of this extreme hemodilution, we could stabilize his hemodynamics and he recovered without any apparent damage in major organs. For management of hemodynamics a massive dose of hydroxyethylated starch (HES) was infused to maintain the intravascular volume. For massive hemorrhage, HES infusion may be useful to keep hemodynamics in spite of progressive hemodilution.

Effect of hydroxyethyl starch 130/0.4 on blood loss and coagulation in patients with recent exposure to dual antiplatelet therapy undergoing off-pump coronary artery bypass graft surgery.

BACKGROUND: Hydroxyethyl starch (HES) solutions are often used for maintaining intravascular volume and improving microperfusion, while a large amount of HES can cause adverse effects on coagulation. As the indications for clopidogrel expand, an increasing number of patients undergoing off-pump coronary artery bypass surgery (OPCAB) are also undergoing dual antiplatelet therapy (DAPT), with its higher risk of bleeding complications. The aim of the present study was to determine whether a moderate dose of 6% HES 130/0.4 significantly increases perioperative blood loss in patients with continued DAPT within 5 days of OPCAB. METHODS AND RESULTS: Patients who received clopidogrel and aspirin within 5 days of OPCAB were randomly allocated to receive HES 130/0.4 (≤ 30 ml/kg) followed by crystalloid infusion (HES group, n=53), or crystalloid only (crystalloid group, n=53) perioperatively. The amount of perioperative blood loss (sum of bleeding during the intraoperative and postoperative 24-h period), transfusion requirements, modified thromboelastography and coagulation variables, hemodynamic parameters, and fluid balance were recorded. Perioperative blood loss and coagulation profiles were similar between the groups, but the postoperative hemoglobin level was higher in the crystalloid group. CONCLUSIONS: Up to 30 ml·kg⁻¹·day⁻¹ of 6% HES 130/0.4 did not increase the perioperative blood loss compared to crystalloid in patients with recent exposure to DAPT undergoing OPCAB. HES 130/0.4 caused a similar degree and duration of coagulation impairment as observed when only crystalloid was given.

[Therapy of acute massive blood loss in a hemophilic patient: case report].

A case is reported of management of massive intraoperative blood loss in a male patient with severe hemophilia. Extirpation of hip pseudotumor with one-stage osteosynthesis with an intramedullary joint-pin in a 43 year old male patient was accompanied with 7.5 l blood loss. The infusion-transfusion therapy (ITT) contained transfusion media about 1/3 of the total volume, fresh-frozen plasma and erythrocyte-containing media were used 1:1. Infusion solutions consisted of balanced polyelectrolytic solutions, hydroxyethylated starches 130/0.4, hyperchaes. Intraoperative normovolemic hemodilution and reinfusion of wound blood were made (CellSaver). ITT target markers were standard hemodynamics control tests. Hemostasis monitoring was conducted with thromboelastography. Complex ITT based on modern principles of clinical transfusiology provided a complete and safe compensation of massive intraoperative blood loss in a patient with severe hemophilia.

To dose or not to dose: that is the (starch) question ...

The present study describes the impact on renal function of a modern starch used for resuscitation in the intensive care unit. The role of starch in renal dysfunction, the importance of the definition of acute kidney injury and acute renal failure, and hyperoncoticity are reviewed.

[Role of 6% hydroxyethylstarch 130/0.4 and furosemide in the treatment of acute pancreatitis].

This study was conducted to observe the effects of intravenously administered 6% hydroxyethylstarch 130/ 0.4 solution and furosemide on the outcome of acute pancreatitis patients. Patients admitted to our center from October 16, 2007 through August 31, 2009 were given intravenous infusions of 6% hydroxyethylstarch 130/0. 4 solution (1 000-2 000 ml administered for an adult) soon after admission. At the same time, furosemide was administered as intravenous bolus, trying to maintain a fluid balance. The dose level of hydroxyethylstarch was gradually lowered from the second day after admission. A total of 135 patients (54% of patients with a Ranson's score > or = 3 and 61% with a Balthazar CT score > or = D) were treated with our protocol. Only 4% and 7% patients developed pancreatic and systemic complications respectively; only 1 patient underwent necrosectomy. The in-hospital mortality rate was 4%. It was estimated that, on the average, 18. 3% of blood volume was lost on admission. Our study suggest that intravenously administered 6% hydroxyethylstarch 130/0. 4 solution and furosemide might be beneficial for patients with acute pancreatitis. Plasma extravasation is a central event of acute pancreatitis. The reversal of hypovolemia is crucial for the success in treatment of acute pancreatitis.

[Advantages of application of hydroxyethylstarch of the III generation during the operations with epidural anesthesia].

Infusion of 1000 ml of 6% hydroxyethylstarch (HES) of the third generation 130/0.42 or crystalloid solutions was conducted to patients before performance of operation on abdominal cavity organs using epidural anesthesia. While HES application the average arterial pressure after induction into anesthesia was less pronounced and concentration of C-reactive protein on the third postoperative day was lesser. It is concluded, that HES 130/0.42 secures the hemodynamic indices stability and reduction of systemic inflammatory reaction severity in the patients and do not influence hemostasis and renal function.

Hydroxyethyl starches: different products--different effects.

With the development of a new generation of hydroxyethyl starches (HES), there has been renewed interest in their clinical potential. High doses of first- and second-generation HES were associated with adverse effects on renal function, coagulation, and tissue storage, thereby limiting their clinical applicability. Newer HES products have lower molar substitution and in vivo molecular weight, resulting in more rapid metabolism and clearance. In this review article, the differences between HES generations are highlighted, with particular emphasis on the improved safety profile of the third generation products. These improvements have been achieved with no loss of efficacy, and they contradict the assumption that efficacy of HES solutions is directly linked to plasma concentration. The impact of source material on structure and pharmacokinetics is highlighted, and the role of the carrier solution is critically assessed.

A randomized comparison of low doses of hyperbaric bupivacaine in combined spinal-epidural anesthesia for cesarean delivery.

BACKGROUND: The aim of our study was to investigate the block characteristics of intrathecal hyperbaric bupivacaine 7, 8, or 9 mg administered during combined spinal-epidural anesthesia for cesarean delivery and to elucidate the dose that produces adequate sensory blockade for surgery while minimizing the incidence of hypotension, high neuroblockade, and the need for intraoperative epidural supplementation. METHODS: Sixty women presenting for elective cesarean delivery were randomly assigned to one of the 3 groups. Group 7 received intrathecal hyperbaric bupivacaine 7 mg, Group 8 received 8 mg, and Group 9 received 9 mg. Women in all 3 groups received intrathecal morphine 100 microg and IV hydroxyethyl starch 15 mL/kg at the time of initiation of combined spinal-epidural anesthesia. Surgery began when a sensory level of T4 was achieved. Patients were monitored for block characteristics and side effects by a blinded observer. Our primary outcome was the maximum cephalad sensory block height. RESULTS: There was a difference in the maximum extent of cephalad sensory block among groups (Group 7: median T2 [interquartile range T2-T3]; Group 8: median T2 [T1-T2]; Group 9: median T1 [C8-T2]; P = 0.02). However, the time taken to reach T4 was similar in all 3 groups. The incidence of hypotension requiring vasopressors was different among groups (30% in Group 7, 55% in Group 8, and 70% in Group 9; P = 0.04). No patient had inadequate anesthesia. Neonatal outcomes were similar in all 3 groups. CONCLUSION: The lowest dose of hyperbaric bupivacaine (7 mg) provided equally rapid onset and effective anesthesia for cesarean delivery while reducing the incidence of hypotension compared with 8 and 9 mg. However, because of its shorter duration of anesthesia, it may be feasible only when the block can be reinforced using a functional epidural catheter.