Feasibility and safety of non-contrast optical coherence tomography imaging using hydroxyethyl starch in coronary arteries.

Intracoronary optical coherence tomography (OCT) requires injection of flushing media for image acquisition. Alternative flushing media needs to be investigated to reduce the risk of contrast-induced renal dysfunction. We investigated the feasibility and safety of pentastarch (hydroxyethyl starch) for clinical OCT imaging. We prospectively enrolled 43 patients with 70 coronary lesions (46-stented; 24-native). Total 81 OCT pullback pairs were obtained by manual injection of iodine contrast, followed by pentastarch. Each pullback was assessed frame-by-frame using an automated customized lumen contour/stent strut segmentation algorithm. Paired images were compared for the clear image segments (CIS), blood-flushing capability, and quantitative morphometric measurements. Overall image quality, as assessed by the proportion of CIS, was comparable between the contrast- and pentastarch-flushed images (97.1% vs. 96.5%; p = 0.160). The pixel-based blood-flushing capability was similar between the groups (0.951 [0.947-0.953] vs. 0.950 [0.948-0.952], p = 0.125). Quantitative two- and three-dimensional morphometric measurements of the paired images correlated well (p < 0.001) with excellent inter-measurement variability. All patients safely underwent OCT imaging using pentastarch without resulting in clinically relevant complications or renal deterioration. Non-contrast OCT imaging using pentastarch is clinically safe and technically feasible with excellent image quality and could be a promising alternative strategy for patients at high risk of renal impairment.

Risk factors for acute kidney injury after major abdominal surgery in the elderly aged 75 years and above.

OBJECTIVES: The study aimed to investigate the incidence and risk factors of acute kidney injury (AKI) in elderly patients (aged ≥ 75 years) undergoing major nonvascular abdominal surgery. METHODS: The study was a retrospective study that evaluated the incidence of AKI in patients within 48 h after major abdominal surgeries. Patients' preoperative characteristics and intraoperative management, including the use of nephrotoxic medications, were evaluated for associations with AKI using a logistic regression model. RESULTS: A total of 573 patients were included in our analysis. A total of 33 patients (5.76%) developed AKI, and 30 (90.91%), 2 (6.06%) and 1 (3.03%) reached the AKI stages 1, 2 and 3, respectively. Older age (adjusted OR, aOR 1.112, 95% confidence interval, CI 1.020-1.212), serum albumin (aOR 0.900, 95% CI 0.829-0.977), baseline eGFR (aOR 3.401, 95% CI 1.479-7.820), the intraoperative occurrence of hypotension (aOR 3.509, 95% CI 1.553-7.929), and the use of hydroxyethyl starch in combination with nonsteroidal anti-inflammatory drugs (aOR 3.596, 95% CI 1.559-8.292) or furosemide (aOR 5.724, 95% CI 1.476-22.199) were independent risk factors for postoperative AKI. CONCLUSIONS: Several risk factors, including intraoperative combined administration of HES and furosemide, are independent factors for AKI during abdominal surgeries. Anesthesiologists and surgeons should take precautions in treating at-risk patients.

Prospective, randomized, controlled, double-blind, multi-center, multinational study on the safety and efficacy of 6% Hydroxyethyl starch (HES) sOlution versus an Electrolyte solutioN In patients undergoing eleCtive abdominal Surgery: study protocol for the PHOENICS study.

BACKGROUND: Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss and to maintain hemodynamic stability. This study was requested by the European Medicines Agency (EMA) to provide more evidence on the long-term safety and efficacy of HES solutions in the perioperative setting. METHODS: PHOENICS is a randomized, controlled, double-blind, multi-center, multinational phase IV (IIIb) study with two parallel groups to investigate non-inferiority regarding the safety of a 6% HES 130 solution (Volulyte 6%, Fresenius Kabi, Germany) compared with a crystalloid solution (Ionolyte, Fresenius Kabi, Germany) for infusion in patients with acute blood loss during elective abdominal surgery. A total of 2280 eligible patients (male and female patients willing to participate, with expected blood loss ≥ 500 ml, aged > 40 and ≤ 85 years, and ASA Physical status II-III) are randomly assigned to receive either HES or crystalloid solution for the treatment of hypovolemia due to surgery-induced acute blood loss in hospitals in up to 11 European countries. The dosing of investigational products (IP) is individualized to patients' volume needs and guided by a volume algorithm. Patients are treated with IP for maximally 24 h or until the maximum daily dose of 30 ml/kg body weight is reached. The primary endpoint is the treatment group mean difference in the change from the pre-operative baseline value in cystatin-C-based estimated glomerular filtration rate (eGFR), to the eGFR value calculated from the highest cystatin-C level measured during post-operative days 1-3. Further safety and efficacy parameters include, e.g., combined mortality/major post-operative complications until day 90, renal function, coagulation, inflammation, hemodynamic variables, hospital length of stay, major post-operative complications, and 28-day, 90-day, and 1-year mortality. DISCUSSION: The study will provide important information on the long-term safety and efficacy of HES 130/0.4 when administered according to the approved European product information. The results will be relevant for volume therapy of surgical patients. TRIAL REGISTRATION: EudraCT 2016-002162-30 . ClinicalTrials.gov NCT03278548.

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.

Third-Generation Hydroxyethyl Starch Causes Dose-Dependent Coagulopathy in Patients Undergoing Off-Pump Coronary Artery Bypass with Continuation of Preoperative Aspirin.

BACKGROUND: We aimed to evaluate the effect of third-generation hydroxyethyl starch (6% HES 130/0.4) on hemostasis and perioperative blood loss in patients undergoing off-pump coronary artery bypass (OPCAB) with continuation of preoperative aspirin. METHODS: Forty-nine consecutive patients, who underwent OPCAB at a single institution between November 1, 2014 and March 31, 2016, were included. Coagulation tests, including thromboelastometry and clinical data of all patients, retrospectively were collected from anesthesia and medical records. RESULTS: The total amount of intraoperative crystalloid and HES was 2057.5 ± 771.6 mL (N = 32) and 1090.6 ± 645.0 mL (N = 32), respectively. In the coagulation pathway, the change ratio of fibrinogen concentration, prothrombin time, and fibrinogen thromboelastometry-maximum clot firmness (FIBTEM-MCF) significantly correlated with HES (P < 0.001, P = 0.00131, and P < 0.001, respectively), but not with crystalloid. In the coagulation pathway concerning interaction with platelets, the change ratio of platelet count, extrinsic thromboelastometry-clotting formation time (EXTEM-CFT), and EXTEM-MCF significantly were correlated with HES (P < 0.001, P < 0.001, and P < 0.001, respectively), but not with crystalloid. At chest closure, the hematocrit decreased in a dose-dependent manner with HES (P < 0.001), but not with crystalloid administration. There was an association between the change ratio of hematocrit and EXTEM-MCF (P = 0.00122). However, intra-postoperative blood loss was not correlated with HES 130/0.4 or crystalloid administration. CONCLUSION: We found that 6% HES 130/0.4 prolonged coagulation testing in a dose-dependent manner due to hemodilution but did not increase blood loss in patients undergoing OPCAB with continuation of preoperative aspirin.

Renal Safety of Hydroxyethyl starch 130/0.42 After Cardiac Surgery: A Retrospective Cohort Analysis.

INTRODUCTION: The risk for renal complications from hydroxyethyl starch 130/0.42 (HES) impacts treatment decisions in patients after cardiac surgery. OBJECTIVE: The objective of this study was to determine the impact of postoperatively administered HES on renal function and 90-day mortality compared to sole crystalloid administration in patients after elective cardiac surgery. METHODS: Using electronic health records from a university hospital, confounding-adjusted models analyzed the associations between postoperative HES administration and the occurrence of postoperative acute kidney injury. In addition, 90-day mortality was evaluated. The impact of HES dosage and timing on renal function on trajectories of estimated glomerular filtration rates over the postoperative period was investigated using linear mixed-effects models. RESULTS: Overall 1009 patients (45.0%) experienced acute kidney injury. Less acute kidney injury occurred in patients receiving HES compared with patients receiving only crystalloids for fluid resuscitation (43.7% vs 51.2%, p = 0.008). In multivariate acute kidney injury models, HES had a protective association (odds ratio: 0.89; 95% confidence interval 0.82-0.96). Crystalloids were not as protective as HES (odds ratio: 0.98; 95% confidence interval 0.95-1.00). There was no association between HES and 90-day mortality (odds ratio: 1.05; 95% confidence interval 0.88-1.25). Renal function trajectories were dose dependent and biphasic, HES appeared to slow down the late postoperative decline. CONCLUSIONS: This study showed no association between HES and the postoperative occurrence of acute kidney injury and thus further closes the evidence gap on HES safety in cardiac surgery patients. Although this was a retrospective cohort study, the results indicated that HES might be safely administered to cardiac surgery patients with regard to renal outcomes, especially if it was administered early and dosed appropriately.

Effect of 6% Hydroxyethyl Starch 130/0.4 on Inflammatory Response and Pulmonary Function in Patients Having Cardiac Surgery: A Randomized Clinical Trial.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass induces a profound inflammatory response that, when severe, can lead to multiorgan system dysfunction. Preliminary data suggest that administration of hydroxyethyl starch (HES) solutions may mitigate an inflammatory response and improve pulmonary function. Our goal was to examine the effect of 6% HES 130/0.4 versus 5% human albumin given for intravascular plasma volume replacement on the perioperative inflammatory response and pulmonary function in patients undergoing cardiac surgery. METHODS: This was a subinvestigation of a blinded, parallel-group, randomized clinical trial of patients undergoing elective aortic valve replacement surgery at the Cleveland Clinic main campus, titled "Effect of 6% Hydroxyethyl Starch 130/0.4 on Kidney and Haemostatic Function in Cardiac Surgical Patients." Of 141 patients who were randomized to receive either 6% HES 130/0.4 or 5% human albumin for intraoperative plasma volume replacement, 135 patients were included in the data analysis (HES n = 66, albumin n = 69). We assessed the cardiopulmonary bypass-induced inflammatory response end points by comparing the 2 groups' serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and macrophage migration inhibitory factor (MIF), measured at baseline and at 1 and 24 hours after surgery. We also compared the 2 groups' postoperative pulmonary function end points, including the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2:Fio2 ratio), dynamic lung compliance, oxygenation index (OI), and ventilation index (VI) at baseline, within 1 hour of arrival to the intensive care unit, and before tracheal extubation. The differences in the postoperative levels of inflammatory response and pulmonary function between the HES and albumin groups were assessed individually in linear mixed models. RESULTS: Serum concentrations of the inflammatory markers (TNF-α, IL-6, MIF) were not significantly different (P ≥ .05) between patients who received 6% HES 130/0.4 or 5% albumin, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). The results of pulmonary function parameters (Pao2:Fio2 ratio, dynamic compliance, OI, VI) were not significantly different (P ≥ .05) between groups, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). CONCLUSIONS: Our investigation found no significant difference in the concentrations of inflammatory markers and measures of pulmonary function between cardiac surgical patients who received 6% HES 130/0.4 versus 5% albumin.

Safety and efficacy of tetrastarches in surgery and trauma: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Hydroxyethyl starch (HES) 130 is a frequently used fluid to replace intravascular losses during surgery or trauma. In the past years, several trials performed in critically ill patients have raised questions regarding the safety of this product. Our aim in this meta-analysis was to evaluate the safety and efficacy of 6% HES during surgery and in trauma. METHODS: This systematic review and meta-analysis was registered at PROSPERO (CRD42018100379). We included 85 fully published articles from 1980 to June 2018 according to the protocol and three additional recent articles up to June 2020 in English, French, German, and Spanish reporting on prospective, randomised, and controlled clinical trials applying volume therapy with HES 130/0.4 or HES 130/0.42, including combinations with crystalloids, to patients undergoing surgery. Comparators were albumin, gelatin, and crystalloids only. A meta-analysis could not be performed for the two trauma studies as there was only one study that reported data on endpoints of interest. RESULTS: Surgical patients treated with HES had lower postoperative serum creatinine (P<0.001) and showed no differences in renal dysfunction, renal failure, or renal replacement therapy. Although there was practically no further difference in the colloids albumin or gelatin, the use of HES improved haemodynamic stability, reduced need for vasopressors (P<0.001), and decreased length of hospital stay (P<0.001) compared with the use of crystalloids alone. CONCLUSIONS: HES was shown to be safe and efficacious in the perioperative setting. Results of the present meta-analysis suggest that when used with adequate indication, a combination of intravenous fluid therapy with crystalloids and volume replacement with HES as colloid has clinically beneficial effects over using crystalloids only.

Hydroxyethyl starch and acute kidney injury in high-risk patients undergoing cardiac surgery: A prospective multicenter study.

BACKGROUND: Hydroxyethyl starch (HES) solutions increase the risk of acute kidney injury (AKI) in critically ill patients admitted to intensive care unit (ICU) for medical indications. We conducted a cohort study to evaluate the renal safety of modern 6% HES solutions in high-risk patients having cardiac surgery. METHOD: In this multicentre prospective cohort study, we recruited 261 consecutive patients at high-risk for developing cardiac surgery-associated AKI, based on a Cleveland score ≥ 4 points, from July to December 2017th in 14 hospitals in Spain and the United Kingdom. Multivariable logistic regression modeling and propensity-score matched-pairs analysis were used to determine the adjusted association between administration of HES and AKI. RESULTS: Of the cohort, 95 patients (36.4%) received 6% HES 130/0.4 either intraoperatively or postoperatively. Postoperative AKI occurred in 145 patients (55.5%). The unadjusted odds of AKI was significantly higher in the HES group, when compared to those not receiving HES (OR 2.22, 95% CI 1.30-3.80, p = 0.003). In multivariable logistic regression models, modern HES was not associated with significantly increased risk of AKI (adjusted OR 0.84, 95% CI 0.41-1.71, p = 0.63). In propensity score match-pairs analysis of 188 patients, the HES group experienced similar adjusted odds of AKI (OR 1.05, CI 95% 0.87-1.27, p = 0.57) and RRT (OR 1.06, CI 95% 0.92-1.22, p = 0.36). CONCLUSIONS: The use of modern hydroxyethyl starch 6% HES 130/0.4 was not associated with an increased risk of AKI nor dialysis in this cohort of patients at elevated risk for developing AKI after cardiac surgery.

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.

Prospective randomized controlled blinded clinical trial evaluating biomarkers of acute kidney injury following 6% hydroxyethyl starch 130/0.4 or Hartmann's solution in dogs.

OBJECTIVE: To evaluate the effect of 6% hydroxyethyl starch (HES) 130/0.4, compared with a Hartmann's solution control (CRYST), on urine biomarkers of acute kidney injury (AKI) in dogs prescribed a fluid bolus. DESIGN: Randomized, controlled, blinded clinical trial January 2018 to February 2019. SETTING: University teaching hospital. ANIMALS: Forty client-owned dogs. INTERVENTIONS: Dogs prescribed a fluid bolus were randomized to receive at least 10 mL/kg of HES or CRYST with clinicians and investigators blinded to fluid type. Study fluid was used for further boluses as required in the following 24 hours, to a limit of 40 mL/kg total, after which fluid administration was open-label. MEASUREMENTS AND MAIN RESULTS: Urine was collected prior to and 6, 12, and 24 hours after the first study fluid bolus. Urine concentrations of AKI biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM), clusterin, and osteopontin were measured using a magnetic bead multiplexed assay. Osmolality-indexed biomarker concentrations were compared between groups over time with linear mixed-effects models, with P < 0.05 considered significant. The mean volume of study fluid administered was not significantly different between groups (HES: 23.1 mL/kg, CRYST: 25.9 mL/kg; P = 0.47, t-test). There were no significant differences between groups in change over time of osmolality-indexed urine concentrations of NGAL (P = 0.91), cystatin C (P = 0.95), KIM (P = 0.77), clusterin (P = 0.63), or osteopontin (P = 0.91). The maximum Veterinary Acute Kidney Injury (VAKI) score up to 7 days during hospitalization (P = 1.0) and in-hospital mortality (P = 0.49) were not significantly different between groups, as compared by Fisher's exact test. CONCLUSIONS: There were no differences in change over time of urine AKI biomarkers in dogs treated with 10 - 40 mL/kg HES or CRYST over 24 hours. Larger clinical trials with patient-centered outcomes are required to investigate the safety of HES in dogs.

Clinical Outcomes and Medical Costs of Hydration Therapy with Hydroxyethyl Starch (130/0.4) or Acute Single Infarction.

OBJECTIVES: To investigate the effects of hydration with or without Hydroxyethyl Starch (HES) 130/0.4 on neurological outcomes and medical costs during hospitalisation in patients with a single infarction (SI) in the posterior lenticulostriate artery (LSA) territory. MATERIALS AND METHODS: In this retrospective, single-centre, non-blinded cohort study, SI in the posterior LSA was defined as an ischaemic lesion with a high-signal intensity area ≥20 mm. All patients received basic stroke care within 48 h of symptom onset between April 2015 and January 2019. Patients were divided into the following two groups by clinician's preference: 1) those administered HES 130/0.4 and 2) those receiving other infusion fluid. The relationships between hospital costs and hydration therapy type were examined. RESULTS: Eighteen (31%) of 58 patients received HES 130/0.4. The HES group had a significantly lower total cost than the control group (3.6 vs. 6.4 million yen, p=0.006). Moreover, the HES group had a significantly shorter hospital stay duration (79.5 vs. 141.0 days) and lower National Institutes of Health Stroke Scale score on day 7. Multivariate analysis found that HES 130/0.4 administration was an independent factor associated with high costs. CONCLUSIONS: Hydration therapy with HES 130/0.4 significantly decreased the total costs and hospitalisation duration of patients with SI in the posterior LSA territory.

Evaluation of postoperative kidney function after administration of 6% hydroxyethyl starch during living-donor nephrectomy for transplantation.

PURPOSE: We aimed to investigate whether 6% HES 130/0.4 was associated with postoperative reduction of estimated glomerular filtration rate (eGFR) in donor patients who underwent nephrectomy for living kidney transplantation. METHODS: This retrospective study included 213 living kidney transplant donors treated at Kyushu University Hospital in Japan from April 2014 to March 2018. Patients who were administered 6% HES 130/0.4 were allocated in the HES group (n = 108), and those who were not were allocated in the control group (n = 105). The postoperative decrements in estimated glomerular filtration rates (eGFRs) from preoperative values were calculated on postoperative days (PODs) 1, 3, and 14. Decline in kidney function (DKF) according to the Kidney Disease: Improving Global Outcomes (KDIGO) classification were analyzed by multivariable-adjusted ordinal logistic regression to estimate odds ratios (ORs) for postoperative DKF. RESULTS: In HES group, administration amount of HES was median 9.4 [interquartile range: 8.2-14.3] ml/kg. Postoperative decrements in eGFR were similar in the control and HES groups on POD 1 (control group: mean 32.0 vs. HES group: 33.0 mL/min/1.73 m2), same as POD 3 (21.1 vs. 22.4 mL/min/1.73 m2) and POD 14 (26.0 vs. 25.9 mL/min/1.73 m2), even after adjusting for confounding factors. The multivariable-adjusted ORs for postoperative DKF did not significantly increase in the HES group on POD 1 (OR: 0.88), POD 3 (OR: 0.96), and POD 14 (OR: 0.52) compared with the control group. CONCLUSION: Six percent HES 130/0.4 is not associated with postoperative renal dysfunction in donor patients undergoing nephrectomy for kidney transplantation.