Ten-year outcomes of Perioperative Anaphylaxis Workup Study in Hong Kong (PAWS-HK): Performance of diagnostic modalities.

BACKGROUND: Studies on perioperative anaphylaxis (PA) in Asia are lacking. Furthermore, allergy workup for PA has largely been limited to the "silver standard" of skin tests (ST). Using in vitro tests as an adjunct to ST may improve and overcome these diagnostic challenges. OBJECTIVE: To evaluate the clinical characteristics and diagnostic tests of patients with suspected PA through the Perioperative Anaphylaxis Workup Study in Hong Kong cohort. METHODS: Patients with a diagnosis of PA over a 10-year period were recruited into the Perioperative Anaphylaxis Workup Study in Hong Kong. We reviewed the medical records, tryptase elevation, and diagnostic tests including ST, specific immunoglobulin E, and basophil activation tests (BAT). RESULTS: In 151 patients with PA, diagnosis was reached in three-fourths of the cases (113/151, 74.8%). The most common culprits identified were neuromuscular blocking agents (25.8%), ß lactams (17.2%) and chlorhexidine (13.9%). Severe anaphylaxis was associated with female sex, older age, elevated acute tryptase levels, and more cardiovascular manifestations during induction. Skin tests remained the most sensitive diagnostic modality overall (66.2%). BAT showed better performance for chlorhexidine and gelofusine anaphylaxis, with sensitivity of 80.0% and 79.6%, respectively. Specific Immunoglobulin E indicated even higher sensitivity (95.2%) than did ST (85.0%) and BAT (80.0%) for chlorhexidine anaphylaxis but performed poorly for other drugs. CONCLUSION: Neuromuscular blocking agents remain the most common culprit in PA. There was a higher prevalence of gelofusine anaphylaxis in our cohort than was seen in the literature. Skin tests remain the most sensitive testing modality. In vitro tests for chlorhexidine and gelofusine showed promising results, but more studies to further elucidate its use are warranted.

99mTc­labeled single-domain antibody for SPECT/CT assessment of HER2 expression in diverse cancer types.

The expression status of human epidermal growth factor receptor 2 (HER2) in cancer predicts response to HER2-targeted therapy. Therefore, its accurate determination is of utmost importance. In recent years, there has been an increase in research on noninvasive techniques for molecular imaging, as this method offers the advantages of a more accurate determination of HER2 status without the need for multiple biopsies. The technetium-labeled single-domain antibody RAD201, previously known as 99mTc-NM-02, has been shown to be safe for use in breast cancer imaging with reasonable radiation doses, favorable biodistribution, and imaging characteristics. METHODS: A total of six HER2-positive, heavily pretreated patients with different cancer types aged between 42 and 69 years (5 women and 1 man; the median age of 55.5) have been examined. In six of seven scans, the patients were administered 500 ml of Gelofusine® solution (40 mg/ml) for radiation protection before the tracer injection (434 ± 42 MBq). Planar scans were acquired with the patient supine at 10 min, 60 min, 160 min, 20 h, and 24 h after injection. A CT scan was acquired at 95 min, followed by local tomographic SPECT imaging. RESULTS: One patient was scanned twice with RAD201, 3 months apart, resulting in a total of seven scans for six patients. Here, we show that the use of RAD201 in our patient group shows the same favorable biodistribution as in a previous study with RAD201 (NCT04040686) and that the radiation dose to the critical organ kidney can be reduced by the application of the plasma expander Gelofusine® by almost 50%. CONCLUSION: RAD201 appears safe for use in humans and is a promising noninvasive tool for discriminating HER2 status in metastatic (breast) cancer, regardless of ongoing HER2-targeted antibody treatment.

[111In]In-CP04 as a novel cholecystokinin-2 receptor ligand with theranostic potential in patients with progressive or metastatic medullary thyroid cancer: final results of a GRAN-T-MTC Phase I clinical trial.

INTRODUCTION: Medullary thyroid cancer (MTC) is a rare malignant tumour of the parafollicular C-cells with an unpredictable clinical course and currently suboptimal diagnostic and therapeutic options, in particular in advanced disease. Overexpression of cholecystokinin-2 receptors (CCK2R) represents a promising avenue to diagnostic imaging and targeted therapy, ideally through a theranostic approach. MATERIALS AND METHODS: A translational study (GRAN-T-MTC) conducted through a Phase I multicentre clinical trial of the indium-111 labelled CP04 ([111In]In-CP04), a CCK2R-seeking ligand was initiated with the goal of developing a theranostic compound. Patients with proven advanced/metastatic MTC or short calcitonin doubling time were enrolled. A two-step concept was developed through the use of low- and high-peptide mass (10 and 50 µg, respectively) for safety assessment, with the higher peptide mass considered appropriate for therapeutic application. Gelofusine was co-infused in a randomized fashion in the second step for the evaluation of potential reduction of the absorbed dose to the kidneys. Imaging for the purpose of biodistribution, dosimetry evaluation, and diagnostic assessment were performed as well as pre-, peri-, and postprocedural clinical and biochemical assessment. RESULTS: Sixteen patients were enrolled. No serious adverse events after application of the compound at both peptide amounts were witnessed; transient tachycardia and flushing were observed in two patients. No changes in biochemistry and clinical status were observed on follow-up. Preliminary dosimetry assessment revealed the highest dose to urinary bladder, followed by the kidneys and stomach wall. The effective dose for 200 MBq of [111In]In-CP04 was estimated at 7±3 mSv and 7±1 mSv for 10 µg and 50 µg CP04, respectively. Administration of Gelofusine reduced the dose to the kidneys by 53%, resulting in the organ absorbed dose of 0.044±0.019 mSv/MBq. Projected absorbed dose to the kidneys with the use of [177Lu]Lu-CP04 was estimated at 0.9±0.4 Gy/7.4 GBq. [111In]In-CP04 scintigraphy was positive in 13 patients (detection rate of 81%) with superior diagnostic performance over conventional imaging. CONCLUSION: In the present study, [111In]In-CP04 was shown to be a safe and effective radiopharmaceutical with promising theranostic characteristics for patients with advanced MTC.

Stimulus-specific functional remodeling of the left ventricle in endurance and resistance-trained men.

Left ventricular (LV) structural remodeling following athletic training has been evidenced through training-specific changes in wall thickness and geometry. Whether the LV response to changes in hemodynamic load also adapts in a training-specific manner is unknown. Using echocardiography, we examined LV responses of endurance-trained (n = 15), resistance-trained (n = 14), and nonathletic men (n = 13) to 1) 20, 40, and 60% one repetition-maximum (1RM), leg-press exercise and 2) intravascular Gelofusine infusion (7 mL/kg) with passive leg raise. While resting heart rate was lower in endurance-trained participants versus controls (P = 0.001), blood pressure was similar between groups. Endurance-trained individuals had lower wall thickness but greater LV mass relative to body surface area versus controls, with no difference between resistance-trained individuals and controls. Leg press evoked a similar increase in blood pressure; however, resistance-trained participants preserved stroke volume (SV; -3 ± 8%) versus controls at 60% 1RM (-15 ± 7%, P = 0.001). While the maintenance of SV was related to the change in longitudinal strain across all groups (R = 0.537; P = 0.007), time-to-peak strain was maintained in resistance-trained but delayed in endurance-trained individuals (1 vs. 12% delay; P = 0.021). Volume infusion caused a similar increase in end-diastolic volume (EDV) and SV across groups, but leg raise further increased EDV only in endurance-trained individuals (5 ± 5 to 8 ± 5%; P = 0.018). Correlation analysis revealed a relationship between SV and longitudinal strain following infusion and leg raise (R = 0.334, P = 0.054); however, we observed no between-group differences in longitudinal myocardial mechanics. In conclusion, resistance-trained individuals better maintained SV during pressure loading, whereas endurance-trained individuals demonstrated greater EDV reserve during volume loading. These data provide novel evidence of training-specific LV functional remodeling.NEW & NOTEWORTHY Training-specific functional remodeling of the LV in response to different loading conditions has been recently suggested, but not experimentally tested in the same group of individuals. Our data provide novel evidence of a dichotomous, training-specific LV adaptive response to hemodynamic pressure or volume loading.

Blood acid-base, haematological and haemostatic effects of hydroxyethyl starch (130/0.4) compared to succinylated gelatin colloid infusions in normovolaemic dogs.

Synthetic colloids are commonly administered to dogs to treat absolute or relative hypovolaemia. Voluven® (tetrastarch 130/0.4) and Gelofusine® (succinylated gelatin) are available to veterinarians in South Africa. In humans, use of these products has caused acid-base derangements, changes in haematology and impaired haemostasis. We aimed to investigate these effects in healthy normovolaemic dogs. Eight healthy adult beagle dogs underwent a cross-over study, receiving Voluven® or Gelofusine® (10 mL/kg/h for 120 min) once each with a 14-day washout between treatments. Dogs were premedicated with dexmedetomidine (10 µg/kg intramuscularly). Anaesthesia was induced with propofol and the dogs were maintained with isoflurane-in-oxygen. The anaesthetised dogs were connected to a multi-parameter monitor to monitor physiological parameters throughout. Catheters placed in a jugular vein and dorsal metatarsal artery allowed sampling of venous and arterial blood. Blood was collected immediately prior to commencement of colloid infusion, after 60 min infusion and at the end of infusion (120 min) to allow for arterial blood gas analysis, haematology and coagulation testing (activated partial thromboplastin time [aPTT], prothrombin time [PT] and thromboelastography [TEG]). There was no effect, between treatments or over time, on blood pH. The haemoglobin concentration, erythrocyte count and haematocrit decreased significantly over time (all p 0.01), with no differences between treatments, and remained within normal clinical ranges. There were no differences between treatments or over time for the TEG, aPTT and PT tests of haemostasis. At the dose studied, Voluven® and Gelofusine® had comparably negligible effects on blood acid-base balance and coagulation in normovolaemic dogs.

Labelling and Clinical Performance of Human Leukocytes Labelled with 99mTc-HMPAO Using Leukokit® with Gelofusine versus Leukokit® with HES as Sedimentation Agent.

The scintigraphy with radiolabelled autologous leukocytes (WBCs) is considered the gold-standard technique for imaging infections. Leukokit® is a commercially available, disposable, sterile kit for labelling WBCs ex vivo. In this kit, WBCs isolation from red blood cells (RBCs) was performed using poly(O-2-hydroxyethyl)starch (HES) as the RBCs sedimentation agent. Due to its poor availability, HES has been recently replaced by Gelofusine as the RBC sedimentation agent. The aim of this study was to compare the labelling efficiency and the diagnostic accuracy of WBCs labelled with Leukokit® with HES vs Leukokit® with Gelofusine. WBCs were isolated using HES or Gelofusine for 45 minutes and then purified from platelets (PLTs) and labelled with 1.1 ± 0.3 GBq of freshly prepared 99mTc-HMPAO. The following parameters were evaluated: the number and type of recovered WBCs, RBCs contamination, PLTs contamination, vitality of neutrophils, and chemotactic properties of neutrophils. Clinical comparison was performed between 80 patients (33 males; age 67.5 ± 14.2) injected with 99mTc-HMPAO-WBCs, using HES as the sedimentation agent, and 92 patients (38 males; age 68.2 ± 12.8) injected with 99mTc-HMPAO-WBCs using Gelofusine as the sedimentation agent. Patients were affected by prosthetic joint infections, peripheral bone osteomyelitis, or vascular graft infection. We compared radiolabelling efficiency (LE), final recovery yield (RY), and diagnostic outcome based on microbiology or 2-year follow-up. Results showed that HES provides the lowest RBCs and PLTs contamination, but Gelofusine provides the highest WBC recovery. Both agents did not influence the chemotactic properties of WBCs, and no differences were found in terms of LE and RY. Sensitivity, specificity, and accuracy were also not significantly different for WBCs labelled with both agents (diagnostic accuracy 90.9%, CI = 74.9-96.1 vs 98.3%, CI = 90.8-100, for HES and Gelofusine, respectively). In conclusion, Gelofusine can be considered a suitable alternative of HES for WBCs separation and labelling.

Drug Carrier-Oriented Polygeline for Preparing Novel Polygeline-Bound Paclitaxel Nanoparticles.

Polygeline is a highly promising drug carrier-oriented material for important applications in pharmacy field due to its low-cost and unique properties similar to albumin. In this study, polygeline-bound paclitaxel nanoparticles (Npb-PTXS) were fabricated through a combination of low-pressure emulsification and high-pressure homogenization. The effects of a series of production parameters on mean particle size, particle size distribution and drug loading of Npb-PTXS were systematically evaluated. The characteristics of Npb-PTXS, such as surface morphology, physical status of paclitaxel (PTX) in Npb-PTXS, redispersibility of Npb-PTXS in purified water and bioavailability in vivo were also investigated. It is revealed that the optimal preparation conditions included an aqueous phase pH value of about 6.5, protein mass concentration of 0.33%, with mass ratio of PTX to protein of 30%, high pressure of 1200 bar, high-pressure passes of 25 times and low-pressure emulsifying passes of 20 times. Obtained Npb-PTXS shows good resolubility compared to commercially available Abraxane®, containing round or oval shaped particles with mean particle size of around 188.3 nm, polydispersity index of 0.163 and zeta potential of -31.1 mV. PTX in Npb-PTX is amorphous, and its content is approximately 12.04%. Encapsulation efficiency of Npb-PTXS reaches 81.2%. Moreover, in vivo pharmacokinetic studies showed that the intravenous relative bioavailability of Npb-PTXS to Abraxane was 83.89%.

Protective effect of Gelofusine against cRGD-siRNA-induced nephrotoxicity in mice.

Based on successful targeting to the αvß3 integrin of cyclic arginine-glycine-aspartic acid (cRGD), cRGD-conjugated small interfering RNA (siRNA) exhibits tumor targeting and has become a new treatment strategy for solid tumors. However, the nephrotoxicity caused by its renal retention limits its clinical application. Here, we evaluated the protective effect of Gelofusine against cRGD-conjugated siRNA-induced nephrotoxicity in mice. Male Kunming mice (six per group) were either co-injected with Gelofusine and cRGD-siRNA or injected with cRGD-siRNA alone. After administration of these treatments five times, creatinine and blood urea nitrogen (BUN) levels were determined. Hematoxylin-eosin staining (HE staining) and transferase dUTP nick end labeling (TUNEL) analysis were used to compare the difference in renal damage between the groups. Additionally, fluorescence imaging was used to observe the distribution of cRGD-siRNA in vivo. The group co-injected with Gelofusine and cRGD-siRNA displayed lower creatinine and BUN levels than the cRGD-siRNA-alone group and showed less renal damage upon HE staining and TUNEL analysis. Gelofusine decreased the retention time and accelerated the elimination of cRGD-siRNA from the organs, as observed in the fluorescence images. These data indicate that Gelofusine significantly increased the excretion of cRGD-conjugated siRNA and reduced the associated renal damage.

Normothermic machine perfusion of donor livers without the need for human blood products.

Normothermic machine perfusion (NMP) enables viability assessment of donor livers prior to transplantation. NMP is frequently performed by using human blood products including red blood cells (RBCs) and fresh frozen plasma (FFP). Our aim was to examine the efficacy of a novel machine perfusion solution based on polymerized bovine hemoglobin-based oxygen carrier (HBOC)-201. Twenty-four livers declined for transplantation were transported by using static cold storage. Upon arrival, livers underwent NMP for 6 hours using pressure-controlled portal and arterial perfusion. A total of 12 livers were perfused using a solution based on RBCs and FFPs (historical cohort), 6 livers with HBOC-201 and FFPs, and another 6 livers with HBOC-201 and gelofusine, a gelatin-based colloid solution. Compared with RBC + FFP perfused livers, livers perfused with HBOC-201 had significantly higher hepatic adenosine triphosphate content, cumulative bile production, and portal and arterial flows. Biliary secretion of bicarbonate, bilirubin, bile salts, and phospholipids was similar in all 3 groups. The alanine aminotransferase concentration in perfusate was lower in the HBOC-201-perfused groups. In conclusion, NMP of human donor livers can be performed effectively using HBOC-201 and gelofusine, eliminating the need for human blood products. Perfusing livers with HBOC-201 is at least similar to perfusion with RBCs and FFP. Some of the biomarkers of liver function and injury even suggest a possible superiority of an HBOC-201-based perfusion solution and opens a perspective for further optimization of machine perfusion techniques. Liver Transplantation 24 528-538 2018 AASLD.

Coagulation in hindbrain membrane meningioma patients treated with different injections using acute hypervolemic hemodilution.

The aim of this study was to analyze the changes in coagulation in meningioma patients treated with different injections using the method of acute hypervolemic hemodilution (AHH). One hundred fifty hindbrain membrane meningioma patients were randomly divided into 5 groups, 30 per group. The first group were injected 40ml/time with Danhong after anesthesia induction; the second group were injected with 40ml~60ml/time Kangai and combined with interventional chemotherapy and embolization procedure; the third group of AHH were injected with polygeline 15ml/kg; the fourth group were injected with hydroxyethyl starch (130/0.4) sodium chloride in doses of 15ml/kg; the control group underwent basic treatment for lowering blood pressure and lowering blood fat. The changes of coagulation index were recorded before and after surgery and before and after the injection of different medications. Compared to the control group, for the first group of AHH, after being treated for 10 days and 30 days, the concentrations of bone specific alkaline phosphatase (BALP), bone Gla protein (BGP) and pro-collagen carboxy-terminal propeptide (PICP) were higher than that of the control group, the levels of endotoxin (ET) and C-reactive protein (CRP) were decreased compared to the control group (p less than 0.05); for the second group of AHH, after being treated for 10 days, the index of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fg) were not significantly changed, but the related level of vascular endothelial growth factor (VEGF) significantly decreased (p less than 0.05). Comparing the coagulation function index after surgery in the third and fourth groups, there were no significant changes in mean arterial pressure (MAP) level, heart rate (HR) value presented a low decrease, central venous pressure (CVP) level increased and the level of interleukin IL-6 showed a steady state after increasing. Analyzing the levels of interleukin IL-8 and tumor necrosis factor-α (TNF-α) after surgery, it was seen that in the third group they increased and in the fourth group they decreased (p less than 0.05). Danhong injection improved the coagulation function and microcirculation of patients, Kangai injection and interventional chemotherapy and embolization restrained the appearance of tumor angiogenesis, AHH operation with polygeline injection and hydroxyethyl starch (130/0.4) sodium chloride kept blood flow in normal parameters.

Gelofusine Ameliorates Colistin-Induced Nephrotoxicity.

Colistin therapy is used as the last line of defense against life-threatening Gram-negative infections. Nephrotoxicity is the major dose-limiting side effect that impedes optimal dosing of patients. This study aims to examine the nephroprotective effect of the plasma volume expander gelofusine against colistin-induced nephrotoxicity. Renal protection was assessed in mice that were subcutaneously injected with colistin sulfate (14 mg/kg of body weight × 6 doses every 2 h; accumulated dose, 84 mg/kg) and simultaneously injected in the intraperitoneal region with gelofusine (75, 150, 300, or 600 mg/kg × 6). At 2 and 20 h after the last colistin dose, mice were euthanized, and the severity of renal alteration was examined histologically. Histological findings in mice revealed that colistin-induced nephrotoxicity was ameliorated by gelofusine in a dose-dependent manner, whereas significant histological abnormalities were detected in the kidneys of mice in the colistin-only group. The impact of coadministered gelofusine on colistin pharmacokinetics was investigated in rats. Rats were administered a single intravenous dose of gelofusine at 400 mg/kg 15 min prior to the intravenous administration of colistin (1 mg/kg). Gelofusine codosing did not alter the pharmacokinetics of colistin in rats; however, gelofusine did significantly lower the accumulation of colistin in the kidney tissue of mice. This is the first study demonstrating the protective effect of gelofusine against colistin-induced nephrotoxicity. These findings highlight the clinical potential of gelofusine as a safe adjunct for ameliorating the nephrotoxicity and increasing the therapeutic index of polymyxins.

Normothermic ex vivo liver perfusion using steen solution as perfusate for human liver transplantation: First North American results.

The European trial investigating normothermic ex vivo liver perfusion (NEVLP) as a preservation technique for liver transplantation (LT) uses gelofusine, a non-US Food and Drug Administration-approved, bovine-derived, gelatin-based perfusion solution. We report a safety and feasibility clinical NEVLP trial with human albumin-based Steen solution. Transplant outcomes of 10 human liver grafts that were perfused on the Metra device at 37 °C with Steen solution, plus 3 units of erythrocytes were compared with a matched historical control group of 30 grafts using cold storage (CS) as the preservation technique. Ten liver grafts were perfused for 480 minutes (340-580 minutes). All livers cleared lactate (final lactate 1.46 mmol/L; 0.56-1.74 mmol/L) and produced bile (61 mL; 14-146 mL) during perfusion. No technical problems occurred during perfusion, and all NEVLP-preserved grafts functioned well after LT. NEVLP versus CS had lower aspartate aminotransferase and alanine aminotransferase values on postoperative days 1-3 without reaching significance. No difference in postoperative graft function between NEVLP and CS grafts was detected as measured by day 7 international normalized ratio (1.1 [1-1.56] versus 1.1 [1-1.3]; P = 0.5) and bilirubin (1.5; 1-7.7 mg/dL versus 2.78; 0.4-15 mg/dL; P = 0.5). No difference was found in the duration of intensive care unit stay (median, 1 versus 2 days; range, 0-8 versus 0-23 days; P = 0.5) and posttransplant hospital stay (median, 11 versus 13 days; range, 8-17 versus 7-89 days; P = 0.23). Major complications (Dindo-Clavien ≥ 3b) occurred in 1 patient in the NEVLP group (10%) compared with 7 (23%) patients in the CS group (P = 0.5). No graft loss or patient death was observed in either group. Liver preservation with normothermic ex vivo perfusion with the Metra device using Steen solution is safe and results in comparable outcomes to CS after LT. Using US Food and Drug Administration-approved Steen solution will avoid a potential regulatory barrier in North America. Liver Transplantation 22 1501-1508 2016 AASLD.

Efficacy of different fluids preload on propofol injection pain: A randomized, controlled, double-blinded study.

Injection pain of propofol remains a common clinical problem. Previous studies demonstrated that propofol injection pain was alleviated by applying nitroglycerin ointment to the skin of injection site, which inspires us to test whether venous vasodilation induced by fluid preload could alleviate the pain. Different types or volumes of fluid preload were compared. 200 ASA I-II adult patients were randomly assigned to five groups of 40 each. A 20 G cannula was established on the dorsum or wrist of the hand. When fluid preload given with Plasma-Lyte A 100 mL (P100 group), 250 mL (P250 group), 500 mL (P500 group), 0.9% saline 500 mL (N500 group) or Gelofusine 500 mL (G500 group) was completed within 30 min, respectively, Propofol (0.5 mg/kg, 1%) was injected at a rate of 0.5 mL/s. A blind investigator assessed the pain using a four-point scale. Incidence of pain in P100, P250, and P500 groups was 87.5%, 57.5% and 35%, respectively (P<0.05). The median pain intensity score was significantly lower in P500 group than that in P250 and P100 groups (P<0.05 and P<0.01, respectively). Comparison of the effect of different types of solution preload indicated that the highest incidence of pain was in N500 group (62.5%) (N500 vs. P500, P=0.014; N500 vs. G500, P=0.007). The median pain intensity score in N500 group was higher than that in P500 group (P<0.05) and G500 group (P<0.05). There was no significant difference between P500 and G500 groups. It is suggested that Plasma-Lyte A or Gelofusine preload with 500 mL before propofol injection is effective in alleviating propofol-induced pain.

Guía de práctica clínica para la elección del fluido de restauración volémica perioperatoria en los pacientes adultos intervenidos de cirugía no cardiaca / Clinical practice guide for the choice of perioperative volume-restoring fluid in adult patients undergoing non-cardiac surgery

Esta Guía de Práctica Clínica responde a preguntas clínicas sobre seguridad en la elección de fluido (cristaloide, coloide o Hidroxietilalmidón 130) en pacientes que precisan restauración volémica en el periodo perioperatorio de cirugía no cardiaca. A partir del resumen de la evidencia, se elaboraron las recomendaciones siguiendo la metodología GRADE. En esta población se sugiere la fluidoterapia basada en la administración de cristaloides, (recomendación débil, calidad de la evidencia baja). En las situaciones en las que la restauración volémica no se alcance sólo con cristaloides, se sugiere utilizar coloides sintéticos (Hidroxietilalmidón 130 o gelatina fluida modificada) en lugar de Albúmina 5% (recomendación débil, calidad de la evidencia baja). La elección y dosificación de coloide deberán basarse en las características del producto, comorbilidad del paciente y experiencia del anestesiólogo (AU)

The present Clinical practice guide responds to the clinical questions about security in the choice of fluid (crystalloid, colloid or hydroxyethyl starch 130) in patients who require volume replacement during perioperative period of non-cardiac surgeries. From the evidence summary, recommendations were made following the GRADE methodology. In this population fluid therapy based on crystalloids is suggested (weak recommendation, low quality evidence). In the events where volume replacement is not reached with crystalloids, the use of synthetic colloids (hydroxyethyl starch 130 or modified fluid gelatin) is suggested instead of 5% albumin (weak recommendation, low quality evidence). The choice and dosage of the colloid should be based in the product characteristics, patient comorbidity and anesthesiologist's experience (AU)

Efficacy of different fluids preload on propofol injection pain: A randomized, controlled, double-blinded study / 华中科技大学学报（医学）（英德文版）

Injection pain of propofol remains a common clinical problem. Previous studies demonstrated that propofol injection pain was alleviated by applying nitroglycerin ointment to the skin of injection site, which inspires us to test whether venous vasodilation induced by fluid preload could alleviate the pain. Different types or volumes of fluid preload were compared. 200 ASA I-II adult patients were randomly assigned to five groups of 40 each. A 20 G cannula was established on the dorsum or wrist of the hand. When fluid preload given with Plasma-Lyte A 100 mL (P100 group), 250 mL (P250 group), 500 mL (P500 group), 0.9% saline 500 mL (N500 group) or Gelofusine 500 mL (G500 group) was completed within 30 min, respectively, Propofol (0.5 mg/kg, 1%) was injected at a rate of 0.5 mL/s. A blind investigator assessed the pain using a four-point scale. Incidence of pain in P100, P250, and P500 groups was 87.5%, 57.5% and 35%, respectively (P<0.05). The median pain intensity score was significantly lower in P500 group than that in P250 and P100 groups (P<0.05 and P<0.01, respectively). Comparison of the effect of different types of solution preload indicated that the highest incidence of pain was in N500 group (62.5%) (N500 vs. P500, P=0.014; N500 vs. G500, P=0.007). The median pain intensity score in N500 group was higher than that in P500 group (P<0.05) and G500 group (P<0.05). There was no significant difference between P500 and G500 groups. It is suggested that Plasma-Lyte A or Gelofusine preload with 500 mL before propofol injection is effective in alleviating propofol-induced pain.

LiDCO-based fluid management in patients undergoing hip fracture surgery under spinal anaesthesia: a randomized trial and systematic review.

BACKGROUND: Hip fracture is a condition with high mortality and morbidity in elderly frail patients. Intraoperative fluid optimization may be associated with benefit in this population. We investigated whether intraoperative fluid management using pulse-contour analysis cardiac monitoring, compared with standard care in patients undergoing spinal anaesthesia, would provide benefits in terms of reduced time until medically fit for discharge and postoperative complications. METHODS: Patients undergoing surgical repair of fractured neck of femur, aged >60 yr, receiving spinal anaesthesia were enrolled in this single-centre, blinded, randomized, parallel group trial. Patients were allocated to either anaesthetist-directed fluid therapy or a pulse-contour-guided fluid optimization strategy using colloid (Gelofusine) boluses to optimize stroke volume. The primary outcome was time until medically fit for discharge. Secondary outcomes included postoperative complications, mobility, and mortality. We updated a systematic review to include relevant trials to 2014. RESULTS: We recruited 130 patients. Time until medically fit for discharge was similar in both groups, mean [95% confidence interval (CI)] 12.2 (11.1-13.5) vs 13.1 (11.9-14.5) days (P=0.31), as was total length of stay 14.2 (12.9-15.8) vs 15.3 (13.8-17.2) days (P=0.32). There were no significant differences in complications, function, or mortality. An updated meta-analysis (four studies, 355 patients) found non-significant reduction in early mortality [relative risk 0.66 (0.24-1.79)] and in-hospital complications [relative risk 0.80 (0.61-1.05)]. CONCLUSIONS: Goal-directed fluid therapy during hip fracture repair under spinal anaesthesia does not result in a significant reduction in length of stay or postoperative complications. There is insufficient evidence to either support or discount its routine use. CLINICAL TRIAL REGISTRATION: ISRCTN88284896.