Hextend (6% hetastarch in lactated electrolyte) / Korea Kolmar, Pfizer, Lineage Cell Therap - LARVOL DELTA

Transition of Resuscitative Endovascular Balloon Occlusion of the Aorta from Zone 3 to Zone 1 to Treat Hemodynamic Collapse during Continued Hemorrhage. (PubMed, Mil Med) - "In this swine model of NCTH, hemodynamics and survival were improved when the REBOA balloon was transitioned from zone 3 to zone 1 during an impending cardiovascular collapse. Furthermore, these improved outcome data support the pursuit of additional research into mitigating ischemia-reperfusion insult to the abdominal viscera while still providing excellent resuscitative support, such as intermittent or partial REBOA."

Journal • Cardiovascular • Hematological Disorders • Reperfusion Injury

Characterization of Combined Blast- and Fragment-Induced Pelvic Injuries and Hemostatic Resuscitation in Rabbits. (PubMed, J Surg Res) - "We herein established in rabbits a blast- and fragment-induced pelvic injury animal model that exhibited high reproducibility, and we demonstrated that hemostatic resuscitation plus DCS was effective in improving the outcome."

Journal • Preclinical

Serum from rats subjected to traumatic brain injury and hemorrhagic shock induces profound endothelial barrier dysfunction. (PubMed, FASEB J) - "These results suggest that exposure to CCI-HS leads to production of humoral factors causing early and late-phase barrier disruptive effects in lung vascular endothelium. While thrombin-PAR1 signaling has been identified as mechanism of acute EC permeability increase by CCI-HS serum, the factor(s) defining long-term EC barrier disruption in CCI-HS model remain to be determined."

Journal • Preclinical • Acute Respiratory Distress Syndrome • CNS Disorders • Hematological Disorders • Pulmonary Disease • Respiratory Diseases • Vascular Neurology

Fluid Resuscitation in Tactical Combat Casualty Care; TCCC Guidelines Change 21-01. 4 November 2021. (PubMed, J Spec Oper Med) - "Presently, an expanding body of literature suggests that fluid resuscitation strategies for casualties in hemorrhagic shock that include the prehospital use of cold-stored or fresh whole blood when available, or blood components when whole blood is not available, are superior to crystalloid and colloid fluids. On the basis of this recent evidence, the Committee on Tactical Combat Casualty Care (TCCC) has conducted a review of fluid resuscitation for the combat casualty who is in hemorrhagic shock and made the following new recommendations: (1) cold stored low-titer group O whole blood (CS-LTOWB) has been designated as the preferred resuscitation fluid, with fresh LTOWB identified as the first alternate if CS-LTOWB is not available; (2) crystalloids and Hextend are no longer recommended as fluid resuscitation options in hemorrhagic shock; (3) target systolic blood pressure (SBP) resuscitation goals have been redefined for casualties with and without traumatic brain injury..."

Journal • CNS Disorders • Hematological Disorders • Vascular Neurology

Trends in Prehospital Blood, Crystalloid, and Colloid Administration in Accordance With Changes in Tactical Combat Casualty Care Guidelines. (PubMed, Mil Med) - "Changes in TCCC guidelines did not immediately translate into changes in prehospital fluid administration practices. Crystalloid fluids continue to dominate as the most commonly administered fluid even after the 2014 TCCC guidelines changed to use of blood products over crystalloids. There should be future studies to investigate the reasons for delay in guideline implementation and efforts to improve adherence."

Clinical • Journal • Hematological Disorders

Unraveling the Cytoprotective Effects of Valproic Acid: A Transcriptomics Meta-Analysis of Transfusion Strategies for Hemorrhagic Shock and Traumatic Brain Injury (ASH 2021) - "In those animal models, VPA was administered in conjunction with fluid resuscitation such as fresh frozen plasma (FFP) or hextend (HEX)... Overall, this meta-analysis suggests that VPA altered the expression of approximately 1/6 th of all genes that were differentially expressed in our cohort. These genes are involved in a variety of biological processes such as cell division, neurogenesis, coagulation, cytoskeleton, and inflammation. These results suggest that VPA treatment may promote an environment that favors the restoration of hemostasis, production of new neurons, removal of damaged cells, and attenuation of inflammation."

Retrospective data • CNS Disorders • Hematological Disorders • Immunology • Inflammation • Vascular Neurology

Efficacy of past, present, and future fluid strategies in an improved large animal model of non-compressible intra-abdominal hemorrhage. (PubMed, J Trauma Acute Care Surg) - "Survival data support the movement away from HEX toward NS and, preferably, FWB in clinical practice and translational animal modeling. The presented model allows for future research including basic science, as well as translational studies of novel diagnostics, therapeutics, and devices."

Journal • Preclinical • Hematological Disorders • Hypotension

"Hetastarch, Hextend, Hydroxyethyl Starch for Postpartum #Hemorrhage #PPH ... #OBAnes #obgyntwitter -- what do you do? WWOBAD @MFMSperling @breinerson @JAMA_current JAMA. 2020;323(3):225-236. doi:10.1001/jama.2019.20833" (@LimGrapes)

Hematological Disorders • Postpartum Hemorrhage

[VIRTUAL] Low Volume Resuscitation with Polyethylene Glycol-20k for Posttraumatic Hemorrhagic Shock in a Hybrid Model of Controlled and Uncontrolled Hemorrhage (ACS-CLINCON 2020) - "When lactate reached 8mmol/L, the tail was clamped and a bolus of PEG-20k, Lactated Ringer’s or Hextend was administered... In this novel rat model of combined controlled and uncontrolled hemorrhagic shock and tissue injury, LVR with PEG-20k was highly effective in restoring blood pressure and tissue perfusion without an additional risk of uncontrolled rebleeding. PEG-20k provides a promising tool that could reduce mortality of severe hemorrhagic shock especially in austere environments with prolonged transport time."

Hematological Disorders

Superior Survival Outcomes of a Polyethylene Glycol-20k Based Resuscitation Solution in a Preclinical Porcine Model of Lethal Hemorrhagic Shock. (PubMed, Ann Surg) - "Superior early and 24-hour outcomes were observed with PEG-20k LVR compared to WB and Hextend in a preclinical porcine model of lethal HS, despite decreased OCC from substantial volume-expansion. These findings demonstrate the importance of enhancing microcirculatory perfusion in early resuscitation strategies."

Journal • Hematological Disorders

Effects of Early Altitude Exposure on the Open Abdomen After Laparotomy in Trauma. (PubMed, Mil Med) - "These results demonstrate the complex interaction of AE and temporary or definitive abdominal closure after post-injury laparotomy. Contrary to our hypothesis, we found that AE in those animals with open abdomens is relatively safe with no difference in mortality compared to those with closed abdomens. However, given the physiologic and inflammatory changes observed in animals with open abdomens, further evaluation is necessary prior to definitive recommendations regarding the safety or downstream effects of exposure to AE prior to definitive abdominal closure."

Journal • Hematological Disorders • Immunology • Metabolic Disorders • Mood Disorders

Effects of Sanguinate® on Systemic and Microcirculatory Variables in a Model of Prolonged Hemorrhagic Shock. (PubMed, Shock) - "Resuscitation with SANGUINATE after PHS improves survival, MAP, and PISFO2 compared to standard of care plasma expanders. Since the pathologies of hemorrhagic shock and the associated systemic ischemia are progressive, preclinical studies of this nature are essential to determine efficacy of new resuscitants across the range of possible times to treatment.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4."

Journal • Gene Therapies • Hematological Malignancies • Reperfusion Injury

Early Identification of Acute Lung Injury in a Porcine Model of Hemorrhagic Shock. (PubMed, J Surg Res) - "Our study demonstrates the reproducibility of a porcine model of hemorrhagic shock that is consistent with physiologic changes in humans in hemorrhagic shock. Pulmonary neutrophil infiltration may serve as an early marker for ALI; however, the practicality of this finding has yet to be determined."

Journal • Preclinical • Acute Lung Injury • Acute Respiratory Distress Syndrome • Hematological Disorders • Mood Disorders

Prehospital whole blood resuscitation prevents coagulopathy and improves acid-base status at hospital arrival in a nonhuman primate hemorrhagic shock model. (PubMed, Transfusion) - "The major benefit of WB, as compared to HEX, in simulated PH resuscitation appears to be prevention of coagulopathy at hospital arrival. Both fluids effectively reversed shock in this model, implying that efficacious provision preload (cardiac output support and hence oxygen delivery) and coagulation proteins (prevention of coagulopathy) are mechanisms underlying WB's effectiveness in early resuscitation of hemorrhagic shock."

Clinical • Journal • Hematological Disorders • Hemophilia • Mood Disorders

Mesenchymal stromal cell secretomes are modulated by suspension time, delivery vehicle, passage through catheter, and exposure to adjuvants. (PubMed) - Cytotherapy - "Exposure of MSCs to certain types of vehicles or additives changes the profile of cytokine secretion. The activation phenotype of MSCs may therefore be affected by the vehicles used for these cells or the exposure to the adjuvants used in their administration."

Journal • Biosimilar

Fresh Frozen Plasma Attenuates Lung Injury in a Novel Model of Prolonged Hypotensive Resuscitation: Plasma and Prolonged Hypotensive Resuscitation. (PubMed, J Trauma Acute Care Surg) - "We have presented a novel model of PHR of military relevance to the PFC environment. In this model, FFP maintains its pulmonary protective effects using a PHR strategy compared to Hextend®, which supports the need for further development and implementation of plasma-based resuscitation in the forward environment."

Journal • MPO

Pre-hospital adenosine, lidocaine and magnesium has inferior survival compared to tactical combat casualty care resuscitation in a porcine model of prolonged hemorrhagic shock. (PubMed, J Trauma Acute Care Surg) - "ALM, as administered in this study, is inferior to current Hextend®-based resuscitation for survival from prolonged hemorrhagic shock in this model. In survivors, ALM groups had lower SBPs and MAPs, but provided a protective effect on coagulopathy as compared to TCCC. ALM does not appear to be a suitable low volume replacement to current TCCC resuscitation. The reduced coagulopathy compared to TCCC warrants future studies of ALM, perhaps as a therapeutic adjunct."

Journal

Whole Blood and Hextend: Bookends of Modern Tactical Combat Casualty Care Field Resuscitation and Starting Point For Multi-functional Resuscitation Fluid Development. (PubMed, J Trauma Acute Care Surg) - "A future multi-functional resuscitative fluid including an asanguineous, oncotic, non-oxygen carrying component to facilitate intra-vascular volume expansion and a component with synthetic coagulation factors and fibrinogen to deter coagulopathy may show equivalence to whole blood."

Journal

Efficacy of the Abdominal Aortic Junctional Tourniquet-Torso Plate in a Lethal Model of Noncompressible Torso Hemorrhage. (PubMed, J Spec Oper Med) - "The AAJT-TP did not provide any survival benefit compared with Hextend alone in this model of noncompressible torso hemorrhage."

Clinical • Journal

Intravenous Hydroxocobalamin Versus Hextend Versus Control for Class III Hemorrhage Resuscitation in a Prehospital Swine Model. (PubMed, Mil Med) - "Moreover, thromboelastography analysis showed longer clotting (K) times (p < 0.05) for the hydroxyethyl starch-treated group. Hydroxocobalamin restored blood pressure more effectively than no treatment and as effectively as hydroxyethyl starch but did not adversely affect coagulation."

Clinical • Journal

Thromboelastographic analysis of novel polyethylene glycol based low volume resuscitation solutions. (PubMed, PLoS One) - "In conclusion, PEG-20k based LVR solutions produced a dose-dependent minor hypocoagulative state, possibly associated with changes in clot propagation and platelet function, which can be reversed by dose reduction in concentration while providing superior LVR, microvascular rescue, and lactate clearance compared to saline or starch."

Journal

Efficacy of the perfluorocarbon dodecafluoropentane as an adjunct to pre-hospital resuscitation. (PubMed, PLoS One) - "DDFPe administration with FFP does not improve survival or enhance tissue oxygenation. However, given similar survival rates of Hextend and FWB, there is evidence that an ideal MRF should contain an element of volume expansion to enhance oxygen delivery."

Clinical • Journal