Colloids Yes or No? - a “Gretchen Question” Answered

Colloid solutions, both natural and synthetic, had been widely accepted as having superior volume expanding effects than crystalloids. Synthetic colloid solutions were previously considered at least as effective as natural colloids, as well as being cheaper and easily available. As a result, synthetic colloids (and HES in particular) were the preferred resuscitation fluid in many countries. In the past decade, several cascading events have called into question their efficacy and revealed their harmful effects. In 2013, the medicines authorities placed substantial restrictions on HES administration in people which has resulted in an overall decrease in their use. Whether natural colloids (such as albumin-containing solutions) should replace synthetic colloids remains inconclusive based on the current evidence. Albumin seems to be safer than synthetic colloids in people, but clear evidence of a positive effect on survival is still lacking. Furthermore, species-specific albumin is not widely available, while xenotransfusions with human serum albumin have known side effects. Veterinary data on the safety and efficacy of synthetic and natural colloids is limited to mostly retrospective evaluations or experimental studies with small numbers of patients (mainly dogs). Large, prospective, randomized, long-term outcome-oriented studies are lacking. This review focuses on advantages and disadvantages of synthetic and natural colloids in veterinary medicine. Adopting human guidelines is weighed against the particularities of our specific patient populations, including the risk–benefit ratio and lack of alternatives available in human medicine.

The Association between Prognostic Nutritional Index (PNI) and Intraoperative Transfusion in Patients Undergoing Hepatectomy for Hepatocellular Carcinoma: A Retrospective Cohort Study

Background: PNI is significantly associated with surgical outcomes; however, the association between PNI and intraoperative transfusions is unknown. Methods: This study retrospectively analyzed 1065 patients who underwent hepatectomy. We divided patients into two groups according to the PNI (<44 and >44) and compared their transfusion rates and surgical outcomes. We performed multivariate logistic and Cox regression analysis to determine risk factors for transfusion and the 5-year survival. Additionally, we found the net reclassification index (NRI) to validate the discriminatory power of PNI. Results: The PNI <44 group had higher transfusion rates (adjusted odds ratio [OR]: 2.20, 95%CI: 1.06–4.60, p = 0.035) and poor surgical outcomes, such as post hepatectomy liver failure (adjusted [OR]: 3.02, 95%CI: 1.87–4.87, p < 0.001), and low 5-year survival (adjusted OR: 1.68, 95%CI: 1.17–2.24, p < 0.001). On multivariate analysis, PNI <44, age, hemoglobin, operation time, synthetic colloid use, and laparoscopic surgery were risk factors for intraoperative transfusion. On Cox regression analysis, PNI <44, MELD score, TNM staging, synthetic colloid use, and transfusion were associated with poorer 5-year survival. NRI analysis showed significant improvement in the predictive power of PNI for transfusion (p = 0.002) and 5-year survival (p = 0.004). Conclusions: Preoperative PNI <44 was significantly associated with higher transfusion rates and surgical outcomes.

O59: USE OF DEXTRAN 40 FOLLOWING PANCREAS TRANSPLANT MAY REDUCE EARLY INFLAMMATION AND SIGNIFICANT BLEEDING COMPARED TO A HEPARIN-BASED PROTOCOL

Introduction Dextran 40 (D40) is a synthetic colloid with anticoagulant properties, which is commonly used instead of heparin following pancreas transplantation, however there is a lack of evidence over which is more effective. Graft thrombosis and pancreatitis, which may be mediated through micro or macrothrombosis within the graft, remain significant complications following pancreas transplantation. We hypothesised that D40 reduces inflammation through its antithrombotic pro-microcirculatory effects. We aimed to evaluate D40 compared to a heparin-based protocol by comparing post-operative complications and post-transplant levels of inflammation. Method Data were collected retrospectively for pancreas transplant patients between December 2009 and August 2018 – 26 patients had been treated with the pre-Dextran protocol and 37 had received D40. Post-operative complications and inflammatory markers (WCC, CRP and amylase) on post-operative days 1, 2, 3 and 7 were compared between the two groups. Potential confounders were also recorded. Result Patients in the D40 group had similar thrombosis rates but were less likely to have had substantial post-operative bleeding compared to the heparin-based protocol. The group who received D40 had significantly lower CRP and WCC on days 2, 3 and 7. The differences on days 3 and 7 remained when the results were adjusted for the significant confounders - cold ischaemic time and donor age. Conclusion D40 appears to be as effective as IV heparin at preventing graft thrombosis following pancreas transplant, and to confer a reduced risk of bleeding. It may also reduce post-operative inflammatory processes, leading to reduced graft pancreatitis. Take-home message Using Dextran 40 as an anticoagulant after pancreas transplantation is as effective as IV heparin at preventing graft thromboses and has a reduced risk of bleeding.

Microvascular Fluid Exchange: Implications of the Revised Starling Model for Resuscitation of Dengue Shock Syndrome

Dengue is the most common mosquito-borne viral infection in the world. The most feared complication is a poorly understood vasculopathy that occurs in only a small minority of symptomatic individuals, especially children and young adults, but can result in potentially fatal dengue shock syndrome (DSS). Based mainly on expert opinion, WHO management guidelines for DSS recommend prompt infusion of a crystalloid fluid bolus followed by a tapering crystalloid fluid regimen, supplemented if necessary by boluses of synthetic colloid solutions. However, following publication of a number of major trials undertaken in other, primarily adult, critical care scenarios, use of both synthetic colloid solutions and of fluid boluses for volume expansion have become controversial. Synthetic colloids tend to be used for severe DSS cases in order to boost intravascular oncotic pressure, based on the classic Starling hypothesis in which opposing hydrostatic and oncotic forces determine fluid flow across the microvascular barrier. However, the revised Starling model emphasizes the critical contribution of the endothelial glycocalyx layer (EGL), indicating that it is the effective oncotic pressure gradient across the EGL not endothelial cells per se that opposes filtration. Based on several novel concepts that are integral to the revised Starling model, we review the clinical features of DSS and discuss a number of implications that are relevant for fluid management. We also highlight the need for context-specific clinical trials that address crucially important questions around the management of DSS.

Hydroxyethyl Starch 130/0.4 Binds to Neutrophils Impairing Their Chemotaxis through a Mac-1 Dependent Interaction

Several studies showed that hydroxyethyl starch (HES), a synthetic colloid used in volume replacement therapies, interferes with leukocyte-endothelium interactions. Although still unclear, the mechanism seems to involve the inhibition of neutrophils’ integrin. With the aim to provide direct evidence of the binding of HES to neutrophils and to investigate the influence of HES on neutrophil chemotaxis, we isolated and treated the cells with different concentrations of fluorescein-conjugated HES (HES-FITC), with or without different stimuli (N-Formylmethionine-leucyl-phenylalanine, fMLP, or IL-8). HES internalization was evaluated by trypan blue quenching and ammonium chloride treatment. Chemotaxis was evaluated by under-agarose assay after pretreatment of the cells with HES or a balanced saline solution. The integrin interacting with HES was identified by using specific blocking antibodies. Our results showed that HES-FITC binds to the plasma membrane of neutrophils without being internalized. Additionally, the cell-associated fluorescence increased after stimulation of neutrophils with fMLP (p < 0.01) but not IL-8. HES treatment impaired the chemotaxis only towards fMLP, event mainly ascribed to the inhibition of CD-11b (Mac-1 integrin) activity. Therefore, the observed effect mediated by HES should be taken into account during volume replacement therapies. Thus, HES treatment could be advantageous in clinical conditions where a low activation/recruitment of neutrophils may be beneficial, but may be harmful when unimpaired immune functions are mandatory.