Hydroxyethyl Starch Infusion Research Articles

Hydroxyethyl-starch (130/0.4/9 and 70/0.55/4) infusion in standing and anesthetized horses

Hydroxyethyl-starch (130/0.4/9 and 70/0.55/4) infusion in standing and anesthetized horses

Prophylactic Epidural Blood Patch or Prophylactic Epidural Infusion of Hydroxyethyl Starch in Preventing Post–Dural Puncture Headache - A Retrospective Study

BACKGROUND: Post–dural puncture headache (PDPH) is particularly likely to happen in patients under obstetric care due to an unintentional dural puncture (UDP). There is as yet no ideal strategy for preventing UDP-induced PDPH. OBJECTIVES: The primary objective of this study was to assess whether a prophylactic epidural blood patch (EBP) or prophylactic epidural infusion of hydroxyethyl starch (HES) is effective in preventing PDPH for parturients with UDP compared with conservative treatments. STUDY DESIGN: Retrospective analysis from a single center’s inpatient data. SETTING: Department of Anesthesiology at a single center. METHODS: A retrospective study was conducted of a single center’s inpatient data from January 2017 through March 2020. The study included parturients with UDP during neuraxial anesthesia. The interventions of UDP included conservative treatment, prophylactic EBP, and prophylactic epidural infusion of HES. The incidence of PDPH, the use of intravenous aminophylline, therapeutic EBP, symptom onset, duration of headache, and duration of hospital stay were compared. RESULTS: A total of 85 patients were analyzed. The incidences of PDPH were 84%, 52.6% and 54.5% with conservative, prophylactic EBP, and prophylactic epidural HES treatments, respectively. Compared with the conservative treatment, prophylactic EBP and prophylactic epidural HES treatment significantly reduced the incidence of PDPH (P < 0.05). No significant difference was found between the prophylactic EBP and prophylactic epidural HES groups. Compared with the conservative treatment group, therapeutic EBP was significantly less used in the prophylactic EBP and prophylactic epidural HES groups (P < 0.05). Prophylactic EBP shortened the length of hospital stay of parturients with UDP (P < 0.05) while prophylactic epidural HES showed no statistical difference compared with conservative treatment. No severe complications, such as central nervous system and puncture site infection or nerve injury, were found in those patients. LIMITATIONS: Retrospective nature and single center data with a relatively small sample size. CONCLUSIONS: Prophylactic management with EBP and epidural infusion of HES has an effect in preventing the occurrence of PDPH; prophylactic EBP significantly shortened hospital stay length in parturients with UDP. KEY WORDS: Unintentional dural puncture, epidural blood patch, hydroxyethyl starch, post–dural puncture headache, parturient

Влияние инфузионной терапии на функцию почек и лабораторные показатели в однодневном эксперименте

Changing views on the composition of infusion therapy in medical practice over the last decade is associated with certain side effects of infusion solutions. It is of relevance to study their influence on the kidneys, metabolism, electrolyte composition and, ultimately, on the patient's treatment results. The aim of the present work is to determine the effect of colloid and crystalloid solutions on renal function and laboratory parameters in experiment. The experimental study was performed on 28 rats (males) of Wistar line. Four experimental groups were formed: I control (n=7) — intact animals (without infusions and laparotomy), II (n=7) — laparotomy without infusions, III (n=7) — laparotomy + infusion of 6 ml of 6% hydroxyethyl starch, IV (n=7) — laparotomy + infusion of 6 ml of 0.9% sodium chloride solution. All animals underwent hematologic and biochemical blood tests, morphologic studies of kidneys. The most pronounced changes in blood tests and morphology were revealed during infusion of 6 ml of 0.9% sodium chloride solution. We observed leukopenia, decreased levels of albumin, cystatin C, cholesterol, alpha-amylase activity, increased concentration of bile acids compared to groups I and II. Morphologic study revealed significant dilatation of capsules of a part of tubules with dilated lumen of their capillaries, irregularly expressed full blood vessels. In addition, displacement of nuclei of nephrothelium to the apical pole of the cell was noted in the absence of homogeneity of cytoplasm with the presence of "enlightenments" in it. Infusion of hydroxyethyl starch did not change the main hematologic and biochemical blood parameters, except for the increase in alpha-amylase activity. Morphologic study did not reveal changes that would lead to acute kidney damage. All changes were reversible. Infusion of physiological solution caused shifts in both hematologic and biochemical blood parameters, in particular, hypoalbuminemia. The results of histologic study indicated redistribution of fluid in the interstitium.

Resuscitative efficacy of hemoglobin vesicles for severe postpartum hemorrhage in pregnant rabbits

We aimed to investigate the resuscitative efficacy of hemoglobin vesicles (HbVs) as a red blood cell (RBC) substitute for the initial treatment of severe postpartum hemorrhage (PPH). Twenty-five pregnant rabbits underwent cesarean section; uncontrolled hemorrhage was induced by transecting the right uterine artery to establish a severe PPH model. During the first 30 min, all rabbits were administered 6% hydroxyethyl starch (HES) of an equivalent volume to the hemorrhage every 5 min. Thereafter, they received any of the following three isovolemic fluids for resuscitation every 5 min: RBCs with platelet-poor plasma (RBC/PPP) (n = 8), 6% HES (n = 7), or HbVs with 25% human serum albumin (n = 10). After surgical hemostasis at 60 min, survival was monitored until 12 h. No rabbits receiving only HES infusion survived beyond 6 h, whereas all rabbits receiving RBC/PPP transfusion survived. The rabbits receiving HbV infusion showed significantly higher mean arterial pressure and hemoglobin levels than the HES-receiving rabbits, and 8 of 10 rabbits survived for 6 h. The HbV group showed significantly higher survival than the HES group but worse survival than the RBC/PPP group. In conclusion, HbV infusion for severe PPH effectively prevents lethal hemorrhagic shock in a pregnant rabbit model.

Stage 1-Biomarkers of Kidney Injury in Dogs Undergoing Constant Rate Infusion of Hydroxyethyl Starch 130/0.4.

Simple SummaryConcern about the use of hydroxyethyl starch (HES) and the development of kidney injury has emerged in human medicine. In veterinary medicine, some retrospective and prospective studies were conducted to investigate the presence of renal damage in dogs using different types and dosages of hydroxyethyl starch. The present study aimed to evaluate the effects of the constant rate infusion of HES 130/0.4 at a dose of 2 mL/kg/h for 24 h on the renal biomarkers of tubular damage and dysfunction. Ten adult dogs with hypoalbuminemia were enrolled, and serum creatinine, fractional excretion of electrolytes, urinary protein to creatinine ratio, urinary albumin to creatinine ratio, qualitative proteinuria, and urinary neutrophil gelatinase-associated lipocalin were measured at the baseline before HES infusion and after 24 and 48 h from the baseline. No significant change in the selected renal biomarkers was observed across time, ruling out the possibility of significant tubular damage after HES 130/0.4 infusion at the dose and rate applied. Further prospective studies are needed to assess the renal safety profile of low-molecular-weight HES administration in more severely affected dogs.In veterinary medicine, investigations relating the effects of hydroxyethyl starch (HES) on renal function report contrasting results. This study aimed to assess the changes in the selected biomarkers of kidney injury in dogs after the administration of HES 130/0.4 as a constant rate infusion (CRI) for 24 h. Ten adult client-owned dogs with hypoalbuminemia (albumin < 2 g/dL) and ongoing fluid losses were included. Enrolled dogs received intravenous fluid therapy with crystalloids and a CRI of HES 130/0.4 at a dose of 2 mL/kg/h for 24 h. Serum creatinine (sCr), fractional excretion (FE) of electrolytes, urinary protein to creatinine ratio (UPC), urinary albumin to creatinine ratio (UAC), SDS-page, and urinary neutrophil gelatinase-associated lipocalin (uNGAL) were measured at the baseline before HES infusion, and after 24 h (T24) and 48 h (T48) from the baseline. No statistically significant difference was found between the baseline value vs. T24 and the baseline vs. T48 for sCr, UAC, UPC, FE of sodium, chloride and calcium, and uNGAL. A significant increase in FEK (p = 0.04) was noticed between the baseline and T48. In this study sample of hypoalbuminemic dogs, HES 130/0.4 at the dose and rate of infusion applied did not cause any significant changes in the investigated biomarkers of kidney injury.

Effect of Loading Changes on the Intraventricular Pressure Measured by Color M-Mode Echocardiography in Rats.

Evaluation of diastolic function is a pivotal challenge due to limitations of the conventional echocardiography, especially when the heart rate is rapid as in rats. Currently, by using color M-mode echocardiography (CMME), intraventricular pressure difference (IVPD) and intraventricular pressure gradient (IVPG) in early diastole can be generated and are available as echocardiographic indices. These indices are expected to be useful for the early diagnosis of heart failure (HF), especially diastolic dysfunction. There have not been any studies demonstrating changes in IVPD and IVPG in response to changes in loading conditions in rats. Therefore, the present study aims to evaluate CMME-derived IVPD and IVPG changes in rats under various loading conditions. Twenty rats were included, divided into two groups for two different experiments, and underwent jugular vein catheterization under inhalational anesthetics. Conventional echocardiography, CMME, and 2D speckle tracking echocardiography were measured at the baseline (BL), after intravenous infusion of milrinone (MIL, n = 10), and after the infusion of hydroxyethyl starch (HES, n = 10). Left ventricular IVPD and IVPG were calculated from color M-mode images and categorized into total, basal, mid-to-apical, mid, and apical parts, and the percentage of the corresponding part was calculated. In comparison to the BL, the ejection fraction, mid-to-apical IVPG, mid IVPG, and apical IVPD were significantly increased after MIL administration (p < 0.05); meanwhile, the end-diastolic volume, E-wave velocity, total IVPD, and basal IVPD were significantly increased with the administration of HES (p < 0.05). The increase in mid-to-apical IVPD, mid IVPD, and apical IVPD indicated increased relaxation. A significant increase in basal IVPD reflected volume overloading by HES. CMME-derived IVPD and IVPG are useful tools for the evaluation of various loading conditions in rats. The approach used in this study provides a model for continuous data acquisition in chronic cardiac disease models without drug testing.

Evaluation of the effects of hydroxyethyl starch (130/0.4) administration as a constant rate infusion on plasma colloid osmotic pressure in hypoabluminemic dogs.

To evaluate the effects of 2 constant rate infusions of hydroxyethyl starch (HES) 130/0.4 on plasma colloid osmotic pressure (COP) in hypoalbuminemic dogs. Prospective, randomized clinical trial. A total of 24 client-owned dogs. Hypoalbuminemic euvolemic dogs (albumin<20g/L[<2g/dL]) with normal perfusion parameters requiring IV fluid therapy were enrolled. In addition to crystalloid, HES 130/0.4 was administered as a constant rate infusion over 24hours at 1mL/kg/h (group 1, n=15) or at 2mL/kg/h (group 2, n=9), in order to support plasma COP. Before infusion, a blood sample was collected to perform CBC, serum electrophoresis, and serologic tests for some infective diseases. Plasma COP, albumin concentration, PCV, and total plasma protein concentration were evaluated serially at baseline (T0) and then at 6, 12, and 24hours after the start of infusion, and a multilevel model was performed for these parameters to detect statistically significant differences between the 2 groups. Twenty-four dogs were included. No statistically significant differences in COP werefound between the 2 groups; however, a high level of variability has been identified within the single individual. Among the other laboratory analyses, PCV was significantly decreased in group 1 at T12 and T24 compared with T0 (P<0.001) and total plasma protein concentration was significantly increased in group 2 at T12 and T24 compared with T0 (P<0.008). No significant effect on plasma COP was found following infusion with HES 130/0.4 at doses of 1mL/kg/h and 2mL/kg/h for 24hours to hypoalbuminemic dogs. The administered concomitant dose of crystalloids, underlying disease, and small sample size were all potential confounding factors.

Effects of anaesthesia-induced hypotension and phenylephrine on plasma volume expansion by hydroxyethyl starch: A randomised controlled study.

Changes in blood haemoglobin concentration indicate plasma volume expansion following hydroxyethyl starch (HES) infusion, but may be affected by vascular tone and HES-induced shedding of the endothelial surface layer (ESL). We hypothesised that anaesthesia-induced hypotension enhances changes in plasma volume as assessed by blood haemoglobin concentration (ΔPVHb , %) following HES infusion. Fifty-two patients undergoing abdominal surgery were randomised to receive a continuous infusion of saline (S group) or phenylephrine to restore vascular tone (P group) (n=26 each). Both groups received an infusion of 8mL/kg 6% HES solution after induction of general anaesthesia. We compared ΔPVHb at the end of fluid infusion (15minutes) and 15minutes later (30minutes) between the two groups. We assessed changes in ESL structure by measuring plasma concentrations of hyaluronate and syndecan-1. P<.05 was considered statistically significant. Mean arterial blood pressure was lower in the S group approximately by 30-40% compared to the P group (P<.001). ΔPVHb was larger in the S group compared to the P group at 15minutes (24.9 [5.2] % vs 19.0 [5.2] %; P<.001) and 30minutes (26.5 [5.9] % vs 16.9 [6.6] %; P<.001). There were no clinically significant differences in plasma concentrations of hyaluronate and syndecan-1 with time and between the groups. Increased volume expansion of circulating plasma following HES infusion in anaesthesia-induced hypotension compared to when blood pressure is restored by phenylephrine may result from an attenuation of transcapillary fluid filtration, rather than ESL shedding. UMIN Clinical Trial Registration Number: UMIN000017394 (http://www.umin.ac.jp/ctr/index.htm).

Large volume infusions of hydroxyethyl starch during cardiothoracic surgery may be associated with postoperative kidney injury: propensity-matched analysis

BackgroundThe safety of intraoperative administration of hydroxyethyl starch (HES) has been debated. We hypothesized that intraoperative use of HES is associated with postoperative acute kidney injury (AKI) following cardiopulmonary bypass (CPB).Materials and methodsPatients who underwent cardiothoracic surgery using CPB between 2007 and 2014 were retrospectively reviewed. The incidence of AKI within 7 days after surgery, defined by the Kidney Disease Improving Global Outcome criteria, was compared for patients who did or did not receive 6% (70/0.5) or 6% (130/0.4) HES for anesthesia management before or after CPB. Multivariable logistic regression and propensity matching analysis were performed to examine whether use of HES is associated with postoperative AKI. Outcomes comparing patients receiving HES ≥ 1000 mL and < 1000 mL were also compared.ResultsData from 1976 patients were reviewed. All patients received 70/0.5 HES as a part of the priming solution for CPB. The incidence of postoperative AKI was 28.2% in patients who received HES and 26.0% in patients who did not (p = 0.33). In multivariable analysis, there was no correlation between the use of HES and the incidence of AKI (odds ratio 0.87, 95% CI 0.30–2.58, p = 0.81). Propensity matching showed that the incidence of AKI was not significantly different between 481 patients administered with HES and 962 patients (26.6% vs. 26.9%, p = 0.95) who did not receive HES for anesthesia management. However, peak creatinine levels, needed for renal replacement therapy, and in-hospital mortality were higher, and 28-day hospital-free days were lower in patients receiving HES ≥ 1000 mL than those receiving HES < 1000 mL (p < 0.05).ConclusionsIntraoperative use of HES was not associated with postoperative AKI following CPB. However, administration of large volumes of HES may be associated with kidney-related adverse clinical outcomes.

Assessment of cerebral and renal autoregulation using near-infrared spectroscopy under normal, hypovolaemic and postfluid resuscitation conditions in a swine model: An observational study.

The impact of blood pressure changes on tissue oxygenation differs between vital organs and with blood volume conditions. To assess cerebral and renal autoregulation simultaneously and compare the impact of blood pressure, hypovolaemia and fluid resuscitation on tissue oxygenation using near-infrared spectroscopy. Animal observational study. An animal laboratory in Hamamatsu University School of Medicine, Hamamatsu, Japan, from April 2018 to August 2018. Fifteen pigs, (mean ± SD) 25.2 ± 0.4 kg. The pigs were anaesthetised with 2.5% isoflurane and phenylephrine 0.5, 1, 2 and 5 μg kg min was administered in a stepwise fashion at 10-min intervals (baseline), followed by similar administration of sodium nitroprusside. Hypovolaemia was induced by a 600-ml bleed (33% of estimated total blood volume). Then phenylephrine was administered again (same protocol). Hypovolaemia was reversed by infusion of 600-ml hydroxyethyl starch. Phenylephrine and sodium nitroprusside were then administered again (same protocol). Average of the relation between mean arterial pressure (MAP) and cerebral or renal tissue oxygenation index (TOI) and individual TOI response during vasoactive drug infusions. The average relationship between MAP and cerebral or renal TOI both showed classic autoregulation patterns, whereas the renal TOI was more pressure-dependent than the cerebral TOI. Hypovolaemia shifted the relationship downward, reducing the cerebral and renal TOIs by approximately 5 and 20%, respectively, at similar MAPs. Subsequent fluid resuscitation preserved the autoregulatory pattern in both organs, not changing cerebral TOI but reducing renal TOI to 10% under baseline. TOI responses in both organs included paradoxical changes (tissue oxygenation changed inversely with MAP) in 60% of animals. Animals with paradoxical reactions maintained more stable cerebral and renal oxygenation. Renal oxygenation is more pressure-dependent than pressure-tolerant cerebral oxygenation, and autoregulation is not robust. Renal oxygenation decreased four-fold compared with cerebral oxygenation during hypovolaemia and two-fold during isovolaemic anaemia. Thus, paradoxical responses are part of normal autoregulatory function and beneficial for maintaining stable oxygenation.

Left ventricular vortex and intraventricular pressure difference in dogs under various loading conditions.

Restrictions on the conventional evaluation of diastolic function have been recognized, especially under various loading conditions. Recently, new noninvasive ventricular vortex indexes have been introduced and are expected to reflect the cardiac function. Physiologically, there is a hypothesis that the intraventricular pressure difference (IVPD) is related to the formation of vortexes. IVPD and vortex indexes were simultaneously measured, and the relationship between the two was investigated. To verify the possibility of diastolic vorticity as an index of diastolic relaxation, a correlation between diastolic vorticity and the load dependency of vorticity [time constant (τ)] was examined. Six healthy dogs were studied using transthoracic echocardiography, pressure, and a conductance catheter. Vorticity was analyzed using vector flow mapping (VFM). IVPD was determined using Euler's equation with color M-mode Doppler images. Data were obtained at baseline, at balloon dilatation in the thoracic aorta to alter afterload, at hydroxyethyl starch infusion to alter preload, and at milrinone administration to alter ventricular relaxation. Peak vorticity at early diastole (E-Vor) and IVPD of the midventricle (MIVPD) decreased under pressure loading, were unchanged under volume loading, and increased during milrinone administration. In multivariate analysis, the independent predictors of τ were global longitudinal strain, strain rate at early diastole, and E-Vor. MIVPD was strongly correlated with E-Vor ( r = 0.84). VFM-derived peak E vorticity was strongly related to IVPD, especially MIVPD, under various loading conditions. Both of these novel indexes are promising as reliable indexes of ventricular relaxation, independent from preload. NEW & NOTEWORTHY We showed the close relationship of vortex and intraventricular pressure difference and showed that both of them can become new markers of the left ventricular relaxation property. Our present study creates a paradigm for future studies in the field of intraventircular flow physiology and clinical diastology.

Effect of restrictive fluid therapy with hydroxyethyl starch during esophagectomy on postoperative outcomes: a retrospective cohort study

BackgroundTo improve prognosis after esophageal surgery, intraoperative fluid optimization is important. Herein, we hypothesized that hydroxyethyl starch administration during esophagectomy reduce the total amount of fluid infused and it could have a positive effect on postoperative complication occurrence and mortality.MethodsAll consecutive adult patients who underwent elective esophageal surgery for cancer were studied. The primary outcome was the development of composite complications including death, cardio-cerebrovascular complications, respiratory complications, renal complications, gastrointestinal complications, sepsis, empyema or abscess, and multi-organ failure. The relationship between perioperative variables and composite complication was evaluated using multivariable logistic regression.ResultsOf 892 patients analyzed, composite complications developed in 271 (30.4%). The higher hydroxyethyl starch ratio in total fluid had a negative relationship with the total fluid infusion amount (r = − 0.256, P < 0.001). In multivariable analysis, intraoperatively administered total fluid per weight per hour (odds ratio, 1.248; 95% CI, 1.153–1.351; P < 0.001) and HES-to-crystalloid ratio (odds ratio, 2.125; 95% CI, 1.521–2.969; P < 0.001) were associated with increased risks of postoperative composite outcomes.ConclusionsAlthough hydroxyethyl starch administration reduces the total fluid infusion amount during esophageal surgery for cancer, intravenous hydroxyethyl starch infusion is associated with an increasing risk of postoperative composite complications.

Effects of crystalloids and colloids on microcirculation, central venous oxygen saturation, and central venous-to-arterial carbon dioxide gap in a rabbit model of hemorrhagic shock

The effects of hydroxyethyl starch (HES) on microcirculation, central venous oxygen saturation (ScvO2), and the central venous-to-arterial carbon dioxide gap (dCO2) are studied in a rabbit model of hemorrhagic shock for elucidating the advantages and drawbacks of resuscitation with HES compared with crystalloids. An ear chamber and sublingual mucosa were used to examine blood vessels by intravital microscopy. Hemorrhagic shock was induced by removing nearly half of the blood volume. Twenty-two rabbits received 20mL of HES by intravenous infusion immediately after bloodletting. Additional HES was then administered intravenously to a total volume of 100mL. The other 22 rabbits (control) were intravenously given 40mL of normal saline solution (NSS), followed by additional NSS to a total volume of 200mL, administered under the same conditions as HES. After the infusion, the vessel density and perfusion rate of the sublingual microcirculation recovered in the HES group. The arteriolar diameter, blood flow velocity, and blood flow rate of the ear microcirculation were maintained in this group, and microcirculatory failure did not develop. In the NSS group, however, all 5 of the aforementioned measured variables were significantly smaller than those in the HES group after the completion of infusion. The recovery of ScvO2 and dCO2 to the respective baseline values was significantly better in the HES group than in the NSS group. Intravenous infusion of HES effectively maintains adequate tissue oxygenation and perfusion in hemorrhagic shock.

Delayed Allergic Cutaneous Hypersensitivity to Icodextrin

Rashes pose a unique challenge to general internists. Here we present a case of a 51-year-old female with end-stage renal disease (ESRD) on peritoneal dialysis who presented to a General Internal Medicine clinic with a vesiculobullous rash on palms and soles 6 months after using icodextrin dialysate, a widely used osmotic agent in peritoneal dialysis. The investigations were positive for an elevated eosinophil count, elevated IgE level and a skin biopsy consistent with an allergic reaction. Her symptoms and labs normalized after stopping icodextrin. There are some reports of allergic reactions to icodextrin which usually occur within a month of initiation of the agent and are self-limiting. Here we hope to report a case of a reaction that occurred 6 months after using icodextrin.&#x0D; Resume&#x0D; Les éruptions cutanées posent un défi particulier aux internistes généraux. Nous rapportons ici le cas d’une femme de 51 ans atteinte d’insuffisance rénale terminale (IRT), sous dialyse péritonéale, qui se présente à une clinique de médecine interne générale avec une éruption cutanée vésiculo-bulleuse sur les paumes et la plante des pieds. Depuis six mois, la patiente utilise un dialysat d’icodextrine, un agent osmotique largement utilisé en dialyse péritonéale. Les analyses ont révélé une numération élevée des éosinophiles, un taux élevé d’IgE et une biopsie cutanée a indiqué la présence d’une réaction allergique. Les symptômes et les résultats d’analyses se sont normalisés après l’arrêt de l’icodextrine. Des réactions d’allergie à l’icodextrine ont déjà été rapportées, mais celles-ci surgissent habituellement dans le mois suivant le début de l’usage de l’agent et se résorbent d’elles-mêmes. Nous désirons signaler un cas de réaction survenue six mois après le début de l’utilisation de l’icodextrine.&#x0D; &#x0D; &#x0D;

Hydroxyethyl starch is associated with early postoperative delirium in patients undergoing esophagectomy

ObjectivePostoperative delirium is associated with longer hospital stay and increased morbidities. Patients undergoing esophagectomy have a high chance of developing postoperative delirium because of their advanced age, comorbidities, and intensive care unit care. In this study, we investigated the risk factors of early postoperative delirium in patients undergoing esophagectomy, focusing on perioperative fluid type to test the hypothesis that colloids with high oncotic pressure and anti-inflammatory action would decrease the incidence of postoperative delirium compared with crystalloids. MethodsAll patients who underwent esophagectomy from 2010 to 2015 in a tertiary care center were reviewed in this retrospective study (n = 1041). Patients who showed positive Confusion Assessment Method or received haloperidol within 4 days postoperatively were enrolled as those with postoperative delirium (+). Multivariable logistic regression was performed to identify risk factors for postoperative delirium. Incidence of postoperative delirium was compared among crystalloids, hydroxyethyl starch, and albumin groups after propensity score matching. ResultsThe incidence of delirium within postoperative 4 days was 22.7%. Infusion of hydroxyethyl starch was an independent risk factor (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.09-2.14; P = .0151). Other risk factors were age (OR, 1.04; 1.02-1.06, per year; P = .0002), preoperative cerebrovascular disease (OR, 2.18; 1.15-4.12; P = .0170), pulmonary dysfunction (OR, 1.85; 1.33-2.58; P = .0003), and transfusion (OR, 1.76; 1.22-2.53; P = .0023). Propensity score matching analysis confirmed that administration of hydroxyethyl starch, but not albumin, is related to postoperative delirium. ConclusionsOld age, preoperative cerebrovascular disease, pulmonary dysfunction, transfusion, and hydroxyethyl starch administration were related to early postoperative delirium. If colloid must be administered, albumin is preferred to hydroxyethyl starch.

Coagulation during elective neurosurgery with hydroxyethyl starch fluid therapy: an observational study with thromboelastometry, fibrinogen and factor XIII

BackgroundSeveral studies have described hypercoagulability in neurosurgery with craniotomy for brain tumor resection. In this study, hydroxyethyl starch (HES) 130/0.42 was used for hemodynamic stabilization and initial blood loss replacement. HES can induce coagulopathy with thromboelastographic signs of decreased clot strength. The aim of this study was to prospectively describe perioperative changes in coagulation during elective craniotomy for brain tumor resection with the present fluid regimen.MethodsForty patients were included. Perioperative whole-blood samples were collected for EXTEM and FIBTEM assays on rotational thromboelastometry (ROTEM) and plasma fibrinogen analysis immediately before surgery, after 1 L of HES infusion, at the end of surgery and in the morning after surgery. Factor (F)XIII activity, thrombin-antithrombin complex (TAT) and plasmin-α2-antiplasmin complex (PAP) were analysed in the 25 patients receiving ≥1 L of HES.ResultsMost patients (37 of 40) received HES infusion (0.5–2 L) during surgery. Preoperative ROTEM clot formation/structure, plasma fibrinogen and FXIII levels were generally within normal range but approached a hypocoagulant state during and at end of surgery. ROTEM variables and fibrinogen levels, but not FXIII, returned to baseline levels in the morning after surgery. Low perioperative fibrinogen levels were common. TAT levels were increased during and after surgery. PAP levels mostly remained within the reference ranges, not indicating excessive fibrinolysis. There were no differences in ROTEM results and fibrinogen levels in patients receiving <1 L HES and ≥1 L HES.ConclusionsOnly the increased TAT levels indicated an intra- and postoperative activation of coagulation. On the contrary, all other variables deteriorated towards hypocoagulation but were mainly normalized in the morning after surgery. Although this might be an effect of colloid-induced coagulopathy, we found no dose-dependent effect of HES. The unactivated fibrinolysis indicates that prophylactic use of tranexamic acid does not seem warranted under normal circumstances in elective neurosurgery. Individualized fluid therapy and coagulation factor substitution is of interest for future studies.

Intraoperative Hydroxyethyl Starch and its Effects on Different Fibrinogen Measurements.

Intravenous fluids with synthetic colloids such as hydroxyethyl starch (HES) are known to interfere with plasma fibrinogen concentration measurements. The aim of this study was to evaluate the effects of an HES solution on fibrinogen measurements in a clinical setting. The study was performed in patients who received at least 1 L of HES during intracranial tumor resection surgery. Blood samples were drawn before the start of surgery (baseline), after infusion of 1 L of HES, and at later time points. The fibrinogen concentration was measured using 3 different methods: (a) enzyme-linked immunosorbent assay (ELISA), (b) Clauss method with a photometric readout, and (c) Clauss method with an electromechanical readout. In addition, the fibrin-based clot quality was evaluated with the thromboelastometric FIBTEM test. Forty patients were enrolled, and 25 patients were included in the analysis. The fibrinogen concentrations at baseline were 2.2, 2.3, and 2.6 g/L and after 1 L of HES 1.6, 1.7, and 1.9 g/L as measured by ELISA, the photometric test, and the electromechanical test, respectively. The electromechanical Clauss test measured significantly higher concentrations at these time points. The relative decrease, however, was comparable between methods (31%, 29%, and 25%, respectively) but significantly lower than the 44% relative decrease with FIBTEM maximum clot firmness. Despite providing different fibrinogen concentration values at baseline, the relative decrease in fibrinogen concentration after HES infusion was comparable among the 3 tests. In contrast, fibrin-based clot quality was more affected than fibrinogen concentration tests by HES infusion.

Impact of hydroxyethyl starch 70/0.5 on acute kidney injury after gastroenterological surgery

BackgroundPrevious studies reported a higher mortality risk and a greater need for renal replacement therapy in patients administered hydroxyethyl starch (HES) rather than other fluid resuscitation preparations. In this study, we investigated the association between 6% HES 70/0.5 use and postoperative acute kidney injury (AKI) in gastroenterological surgery patients.MethodsWe conducted retrospective full-cohort and propensity-score-based analyses of patients who underwent gastroenterological surgery between June 2011 and August 2013 in a Japanese university hospital. The study sample comprised 66 AKI and 2,152 non-AKI patients in the full-cohort analysis and 35 AKI and 1,269 non-AKI patients in the propensity-score-based analysis. Propensity scores were calculated using an ordered logistic regression model in which the dependent variable comprised three groups based on HES infusion volumes (0, 1–999, and ≥ 1,000 ml). The association between HES groups and postoperative AKI incidence was analyzed using multiple logistic regression models. Other candidate independent variables included patient characteristics and intraoperative measures.ResultsIn the full-cohort analysis, 40 (60.6%) AKI patients were diagnosed as "risk", 15 (22.7%) as "injury," and 11 (16.7%) as "failure". In the propensity-score-based analysis, the corresponding values were 22 (62.9%), 8 (22.9%), and 5 (14.3%). There was no significant association between total infused HES and postoperative AKI incidence in either the full-cohort or the propensity-score-based analysis (P = 0.168 and P = 0.42, respectively).ConclusionsAKI incidence was not associated with clinical 6% HES 70/0.5 administration in gastroenterological surgery patients treated at a single center.

Impact of high doses of 6% hydroxyethyl starch 130/0.42 and 4% gelatin on renal function in a pediatric animal model.

Despite serious renal side effects in critically ill adult patients, artificial colloids are still fundamental components of perioperative fluid therapy in infants and children, although the impact of 6% hydroxyethyl starch (HES) and 4% gelatin (GEL) on renal function during pediatric surgery has not been identified yet. To determine the impact of high doses of artificial colloids on renal function, we conducted an experimental animal study and hypothesized that neither the infusion of HES nor of GEL would have a serious impact on renal function. Fifteen sedated piglets were randomly assigned to receive an infusion of either 50 ml · kg(-1) HES or GEL, or a balanced electrolyte solution (crystalloid group). Before and 1 week after infusion, serum and urine renal function tests were recorded and renal biopsies were taken. Serum and urine renal function tests revealed no increase after administration of HES and GEL, and only a discrete increase in serum creatinine (median 9.8 μmol · l(-1), 95% CI 4.0-19.1) in the crystalloid group. Histopathological examination indicated a sparsely, multifocal infiltration of mononuclear cells in all groups and an unspecific pyelectasia of one animal in the GEL group. After high doses of HES or GEL in piglets, no relevant impact on renal function could be found. These results confirm that AKI after HES or GEL is very unlikely in hemodynamically stable perioperative patients with normal renal function.

The Influence of Hypovolemia and Fluid Resuscitation During Hemorrhagic Shock on Apneic Oxygen Desaturation After Preoxygenation in a Swine Model.

Patients experiencing major bleeding often require both aggressive fluid resuscitation and rapid sequence tracheal intubation. The influence of hemorrhage-induced hypovolemia, and/or subsequent fluid resuscitation, on the time until critical oxygen desaturation is not well described. We studied the time to oxygen desaturation in a pig model of hemorrhage shock and colloid resuscitation. After anesthetic induction with isoflurane, 9 swine (mean ± SD = 25.3 ± 0.6 kg) were studied with the use of a stepwise hemorrhage and fluid resuscitation model with 4 sequential stages: 600 mL hemorrhage, 600 mL hydroxyethyl starch infusion, a further 600 mL hemorrhage, and a second 600 mL hydroxyethyl starch infusion. At each stage, after 5 minutes of mechanical ventilation with 100% oxygen, we induced apnea and measured the time to oxygen desaturation (oxygen saturation [SpO2] <70%). Hemodynamic and blood gas variables were recorded, and the cerebral and peripheral tissue oxygenation indices were recorded by near-infrared spectroscopy. The times ± SD to SpO2 <70% at each stage were 136 ± 41 (baseline), 147 ± 41 (hemorrhage), 131 ± 38 (resuscitation), 147 ± 38 (repeat hemorrhage), and 134 ± 36 seconds (repeat resuscitation). The mean differences in times before and after hemorrhage were 11.2 (6.5 to 16.0, P = 0.0052) and 16.0 (11.0 to 21.0, P < 0.0001), respectively. PaO2 before and after apneic desaturation (at SpO2 < 70%) was not different between stages. On the basis of tissue oxygenation index findings, hypovolemia decreased oxygen consumption, and fluid resuscitation recovered this parameter. In patients with acute hemorrhagic shock, a hypovolemic state increases the duration of apnea until critical oxygen desaturation. Clinicians should thus consider the relationship between fluid resuscitation and time to desaturation when performing tracheal intubation in such patients.