[Viscoelasticity-based point of care coagulation diagnostics in the context of resuscitation room management of severely injured and bleeding trauma patients : Diagnostics and treatment of trauma-induced coagulopathy]. / Viskoelastizitätsbasierte "Point-of-care"-Gerinnungsdiagnostik im Kontext des Schockraummanagements von blutenden Traumapatienten : Diagnostik und Therapie der traumainduzierten Koagulopathie.

Uncontrolled bleeding with associated trauma-induced coagulopathy (TIC) remains the leading cause of preventable death after severe trauma. Meanwhile, TIC is recognized as a separate clinical entity with substantial impact on downstream morbidity and mortality. In clinical practice severely injured and bleeding patients are often still being treated according to established damage control surgery (DCS) procedures with surgical bleeding control and empirical transfusion of classical blood products in predefined ratios in the sense of damage control resuscitation (DCR); however, algorithms are also available, which have been constructed from established viscoelasticity-based point of care (POC) diagnostic procedures and target value-oriented treatments. The latter enables a timely qualitative assessment of coagulation function from whole blood at bedside and provides rapid and clinically useful information on the presence, development and dynamics of the coagulation disorder. The early implementation of viscoelasticity-based POC procedures in the context of resuscitation room management of severely injured and bleeding patients was uniformly associated with reductions in potentially harmful blood products, especially overtransfusions, and an overall improvement in outcome including survival. The present article reviews the clinical questions around the use of viscoelasticity-based procedures as well as recommendations for the early and acute management of bleeding trauma patients taking the current literature into account.

Evaluation of a single-shot of a high-density viscoelastic solution of hyaluronic acid in patients with symptomatic primary knee osteoarthritis: the no-dolor study.

BACKGROUND: Pronolis®HD mono 2.5% is a novel, one-shot, high-density sterile viscoelastic solution, recently available in Spain, which contains a high amount of intermediate molecular weight hyaluronic acid (HA), highly concentrated (120 mg in 4.8 mL solution: 2.5%). The objective of the study was to analyze the efficacy and safety of this treatment in symptomatic primary knee osteoarthritis (OA). METHODS: This observational, prospective, multicenter, single-cohort study involved 166 patients with knee OA treated with a single-shot of Pronolis®HD mono 2.5% and followed up as many as 24 weeks. RESULTS: Compared with baseline, the score of the Western Ontario and McMaster Universities Arthritis Osteoarthritis Index (WOMAC) pain subscale reduced at the 12-week visit (primary endpoint, median: 9 interquartile range [IQR]: 7-11 versus median: 4; IQR: 2-6; p < 0.001). The percentage of patients achieving > 50% improvement in the pain subscale increased progressively from 37.9% (at 2 weeks) to 66.0% (at 24 weeks). Similarly, WOMAC scores for pain on walking, stiffness subscale, and functional capacity subscale showed significant reductions at the 12-week visit which were maintained up to the 24-week visit. The EuroQol visual analog scale score increased after 12 weeks (median: 60 versus 70). The need for rescue medication (analgesics/nonsteroidal anti-inflammatory drugs) also decreased in all post-injection visits. Three patients (1.6%) reported local adverse events (joint swelling) of mild intensity. CONCLUSIONS: In conclusion, a single intra-articular injection of the high-density viscoelastic gel of HA was associated with pain reduction and relief of other symptoms in patients with knee OA. TRIAL REGISTRATION: ClinicalTrial# NCT04196764.

Thromboembolic complications in critically ill COVID-19 patients are associated with impaired fibrinolysis.

BACKGROUND: There is emerging evidence for enhanced blood coagulation in coronavirus 2019 (COVID-19) patients, with thromboembolic complications contributing to morbidity and mortality. The mechanisms underlying this prothrombotic state remain enigmatic. Further data to guide anticoagulation strategies are urgently required. METHODS: We used viscoelastic rotational thromboelastometry (ROTEM) in a single-center cohort of 40 critically ill COVID-19 patients. RESULTS: Clear signs of a hypercoagulable state due to severe hypofibrinolysis were found. Maximum lysis, especially following stimulation of the extrinsic coagulation system, was inversely associated with an enhanced risk of thromboembolic complications. Combining values for maximum lysis with D-dimer concentrations revealed high sensitivity and specificity of thromboembolic risk prediction. CONCLUSIONS: The study identifies a reduction in fibrinolysis as an important mechanism in COVID-19-associated coagulopathy. The combination of ROTEM and D-dimer concentrations may prove valuable in identifying patients requiring higher intensity anticoagulation.

A novel injectable starch-based tissue adhesive for hemostasis.

Hemorrhage remains one of the direct causes of high mortality. The development of ideal hemostatic materials with sound ability to deal with severe wound is urgent needed. Although starch-based hemostatic powder has been widely used, hydrous physiological environments severely hamper its binding to the target tissue, thereby limiting the effectiveness in hemostasis. Herein, inspired by mussel adhesive protein, a novel injectable tissue-adhesive hydrogel (St-Dopa hydrogel) composed of starch, succinic anhydride and dopamine was developed in situ by enzymatic crosslinking. The results show that St-Dopa hydrogels were intimately integrated with biological tissue and formed robust barriers to reduce blood loss. St-Dopa hydrogels exhibited superior capacity for in vitro and in vivo hemostasis as compared with chitin hydrogels. In addition to the ease of operation, St-Dopa hydrogels exhibited rapid sol-gel transition, porous microscopic morphology, good swelling ratio and biodegradability, tissue-like elastomeric mechanical properties and excellent cyto/hemo-compatibility. These results suggest that this newly developed St-Dopa hydrogel is a promising biological adhesive and hemostatic material.

Internal Limiting Membrane Transposition for Persistent Macular Holes Using Double Layers of Viscoelastic.

Internal limiting membrane (ILM) grafting provides a useful option for repair of large and refractory macular holes that fail to close following prior ILM removal. However, current ILM graft techniques are associated with several challenges that may result in failure, most notably the difficulty in maintaining the graft in situ. In this video, the authors describe their modified technique for ILM grafting using a double layer of viscoelastic for stabilization in situ during the procedure. Four of five eyes managed with this technique demonstrated type 1 closure, and all eyes demonstrated improvement in visual acuity.

Corneal Wound Healing Effects of Mesenchymal Stem Cell Secretome Delivered Within a Viscoelastic Gel Carrier.

Severe corneal injuries often result in permanent vision loss and remain a clinical challenge. Human bone marrow-derived mesenchymal stem cells (MSCs) and their secreted factors (secretome) have been studied for their antiscarring, anti-inflammatory, and antiangiogeneic properties. We aimed to deliver lyophilized MSC secretome (MSC-S) within a viscoelastic gel composed of hyaluronic acid (HA) and chondroitin sulfate (CS) as a way to enhance corneal re-epithelialization and reduce complications after mechanical and chemical injuries of the cornea. We hypothesized that delivering MSC-S within HA/CS would have improved wound healing effects compared the with either MSC-S or HA/CS alone. The results showed that a once-daily application of MSC-S in HA/CS enhances epithelial cell proliferation and wound healing after injury to the cornea. It also reduced scar formation, neovascularization, and hemorrhage after alkaline corneal burns. We found that combining MSC-S and HA/CS increased the expression of CD44 receptors colocalized with HA, suggesting that the observed therapeutic effects between the MSC-S and HA/CS are in part mediated by CD44 receptor upregulation and activation by HA. The results from this study demonstrate a reproducible and efficient approach for delivering the MSC-S to the ocular surface for treatment of severe corneal injuries. Stem Cells Translational Medicine 2019;8:478-489.

Implante de hilano GF20 ̈ para el tratamiento de gonoartrosis / HF implant GF 20 ̈ for the treatment of osteoarthritis

INTRODUCCIÓN: Este documento técnico se realiza a solicitud del Hospital Nacional Arzobispo Loayza a través de la de la Gerencia Macro Regional Centro Medio del Seguro Integral de Salud. a) Cuadro clínico La gonoartrosis (GA) es una afección inflamatoria crónica, degenerativa y progresiva que afecta a pacientes usualmente después de los 40 años de edad, siendo más frecuente en mujeres. Su presentación clínica es variable, siendo el síntoma más frecuente el dolor articular de la rodilla, pudiendo presentarse con rigidez o crepitación al movimiento. Las alternativas de tratamiento son variables pudiendo ser terapias conservadoras o las modificadoras de enfermedad como glucosamina, medicamentos de residuos insaponificables, plasma rico en plaquetas e implante de ácido hialurónico. Además, en casos severos incapacitantes, la cirugía puede estar indicada. b) Tecnología sanitaria El implante de hilano GF20 ̈ (IH) (Synvisc, Synvisc One) es un fluido elastoviscoso que, por su contenido de hilanos, es biológicamente similar al hialuronato (componente del líquido sinovial responsable de la elastoviscosidad de la articulación). Por lo tanto, se ha propuesto que la aplicación del IH puede sustituir o suplementar el líquido sinovial (viscosuplementación), restaurando el estado fisiológico de los tejidos de la articulación afectada en la GA. OBJETIVO: Evaluar la eficacia y seguridad, así como documentos relacionados a la decisión de cobertura del implante de hilano GF20 ̈ para el tratamiento de gonoartrosis. METODOLOGÍA: Se realizó una búsqueda en las principales bases de datos bibliográficas: MEDLINE (PubMed), LILACS, COCHRANE, así como en buscadores genéricos de Internet incluyendo Google Scholar y TRIPDATABASE. Adicionalmente, se hizo una búsqueda dentro de la información generada por las principales instituciones internacionales de reumatología y agencias de tecnologías sanitarias. Se priorizaron ensayos clínicos aleatorizados (ECAs), revisiones sistemáticas (RS), evaluaciones de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC). RESULTADOS: Se seleccionaron tres RS, un ECA, cinco GPC y dos ETS. CONCLUSIONES: Los estudios que comparan IH frente a CS muestran que IH es equivalente o mejor que CS en escalas de dolor e índices de enfermedad. Sin embargo, se encuentra que los pacientes con IH presentan mayor riesgo de eventos adversos, es su mayoría asociados a la piel. Se identificaron estudios que comparaban IH con placebo y ácido hialurónico de bajo peso molecular, pero debido a su alta heterogeneidad los resultados combinados son inciertos. La mayoría de las GPC no recomienda el uso de IH en el manejo de GA. Sólo una GPC recomienda IH como una alternativa en pacientes con falla de tratamiento de primera línea. La ETS elaborada por IETSI considera la evidencia de baja calidad como para incluir la tecnología en su lista de cobertura mientras que otra ETS de Canadá, a través de un análisis indirecto con evidencia de baja calidad, encuentra que IH es equivalente a otras alternativas y mejor que la terapia estándar; sin embargo, no es costo-efectiva para la institución.

Using a New Photo Scale to Compare Product Integration of Different Hyaluronan-Based Fillers After Injection in Human Ex Vivo Skin.

BACKGROUND: The rheological properties of HA products have been investigated thoroughly, and these properties have been used to predict the clinical performance of HA fillers. It has been suggested that firm gels have a better ability to withstand deformation, and softer gels have been claimed to integrate and spread more into the tissue since they are perceived to deform more easily. However, the scientific published data regarding product integration of filler products with different physicochemical properties is limited. Thus, there is a need to improve the understanding regarding links between rheological properties of the gel material and the clinical performance. OBJECTIVE: The objectives of this study were: to develop and validate a photo scale for assessment of product distribution after intradermal injection, and to evaluate if product differences, such as overall rheological properties, gel particle size, swelling factor, and cohesivity effect the product distribution into the tissue after intradermal injections. MATERIAL AND METHODS: Intradermal injections of HA fillers were performed in ex vivo human abdominal skin samples. The skin samples were processed for histological evaluation. In order to evaluate the product integration after intradermal injection and compare the results between different products a 5-grade product integration scale (from 0 to 4) was developed based on representative microphotographs. The scale was validated and used for the evaluation of integration of the different products used in the study. The results were correlated with the rheological properties of the different products. RESULTS: G', the elastic modulus, is one important rheological parameter. Strong and firm gels have higher G' than weak and soft gels. When plotting the G' to mean product integration score in human skin obtained in the study, there was a statistically significant correlation with products with lowest G' having the highest integration score and products with high G' having the lowest integration scores. No statistical correlation could be seen when analyzing the score versus particle size, swelling factor, and cohesivity. CONCLUSION: The degree of product integration can be assessed and scored according to a 5-grade visual scale based on representative microphotographs. Products with different rheological properties distribute differently when injected into the skin. Firmer gel texture resulted in more targeted product integration whiles softer gel texture resulted in distributed product integration. J Drugs Dermatol. 2018;17(9):982-986.

A Single Site, Open Label Clinical Trial, Evaluating the Duration, Efficacy, and Safety of a Novel Lip Plumper.

INTRODUCTION: Lip plumpers are topical agents that offer immediate, but temporary, volumization of the lips. While these products are becoming increasingly popular and are available at multiple retailers, there is a lack of clinical studies to evaluate the efficacy, longevity, and safety of the lip plumping products. METHODS: This is a prospective, single center, clinical trial to evaluate the duration, efficacy, and safety of a lip plumping agent in two clinical visits. Lip volume and adverse event were assessed by two clinicians at various time points: 15 minutes, 1 hour, 2 hours, 3 hours, and 4 hours. RESULTS: Twenty-two subjects were enrolled in the study, and eighteen completed the study. Investigator assessments of global improvement 15 minutes after application of the lip plumping product demonstrated improvement in lip fullness in 100% of the subjects (18/18), and 1 hour post-application 67% (12/18) showed an improvement in lip fullness that was statistically significant compared to the 2-hour assessment (P less than 0.05). Subject evaluations noted improvement in lip fullness 15 minutes post-application in 94.4% (17/18) of subjects, and 1 hour post-application, 89% (16/18) of the subjects who completed the trial noted some improvement in the volume of their lips that was statistically significant compared to the 2-hour post-application time point (P less than 0.0001). Subjects noted that they did experience a tingling and heat sensation, but a majority noted that that this sensation lasted less than 15 minutes. DISCUSSION: Our study demonstrated that the lip plumping product increased lip volume in almost all patients 15 minutes post-application and showed a continued improvement in lip fullness per investigator assessments 1 hour after application. Adverse events of a tingling or heat sensation were expected and observed as the topical product contained capsaicin, cinnamon, and menthol, all of which can induce this sensation by the release of substance P. J Drugs Dermatol. 2018;17(9):999-1004.

Facial Volumetric Structural Rejuvenation: A Natural Approach to Restoring Youthfulness and Preventing Aging.

When rejuvenating the face with soft tissue fillers, one must consider its structural framework, and patient specific goals/needs holistically to achieve natural results.

Comparison of Floaters after Cataract Surgery with Different Viscoelastics.

Purpose: To investigate whether there is a difference between symptoms of floaters according to the type of ophthalmic viscosurgical devices(OVDs) used during phacoemulsification. Methods: A total of 112 eyes had undergone standard phacosurgery with the dispersive OVDs(Group1). Group2 comprised 117 eyes that underwent phacosurgery with the dispersive OVDs, but between continuous curvilinear capsulorhexis and hydrodissection, some OVDs had been removed. Group3 included 120 eyes that had undergone phacosurgery with the cohesive OVDs. Results: 14 eyes (12.5%) of Group1 had new-onset floater after surgery whereas 6 eyes (5.13%) in Group2, and 7 eyes (5.83%) in Group3 at the day after and a week after surgery. This was significantly higher in Group1 than Group2 and Group3, respectively (p=0.047,0.049). Conclusion: Cataract surgery with dispersive OVD can predispose the eye to an increased floater symptom. Therefore, surgeons should consider release some OVDs during hydrodissection with dispersive viscoelastics and keep trying to avoid IOP surge during surgery.

Effects of phacoemulsification with versus without viscoelastic devices on surgical outcomes.

PURPOSE: The aim of this study is to report surgical outcomes in patients undergoing phacoemulsification surgery (PE) with versus without ophthalmic viscosurgical devices (OVDs). METHODS: This is a comparative case series study. In total, 145 patients who performed PE with OVDs in 68 eyes (Group 1) and without OVD in 77 eyes (Group 2) were enrolled. A comprehensive ophthalmological examination was performed including slit-lamp, fundus examination. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) specular endothelial microscopy (SM), and ultrasound pachymetry (UP) were also measured before surgery and at four-time points postoperatively. The differences in baseline characteristics as well as in outcomes were compared between the two groups. RESULTS: The mean BCVA was 0.41 ± 0.26 logMAR in Group 1 and 0.54 ± 0.34 in Group 2 at postoperative first day, with a significant difference (p < 0.01). The mean BCVA, IOP, and UP at 6 months did not differ between the groups. The mean baseline and postoperative SMs were 2063 and 1910 cells/mm2, respectively, and the endothelial cell loss (ECL) was 153.89 ± 189 in Group 1. The mean baseline and postoperative SMs were 2153 and 1948 cells/mm2, respectively, and the ECL was 205 ± 200 in Group 2. The difference between the groups was not statistically significant (p = 0.105). CONCLUSIONS: The ECL seemed to be higher in the Group 2, but the difference was not significant. The final clinical outcomes were similar between the groups. In selected cases, PE without OVD may be preferable to reduce the cost of surgery in places with low economic status and to prevent side-effects of these devices.

The Efficacy of a Viscoelastic Foam Overlay on Prevention of Pressure Injury in Acutely Ill Patients: A Prospective Randomized Controlled Trial.

PURPOSE: The purpose of this study was to compare a viscoelastic foam overlay (VEFO) to a standard hospital mattress for pressure injury (PI) prevention. We also compared interface pressures (IPs) of the VEFO to our facility's standard hospital mattress. DESIGN: Prospective, randomized controlled trial. SUBJECTS AND SETTING: Data analysis was based on 110 participants (55 in each group) who were 19 years or older, had a Braden Scale for Pressure Sore Risk score of 16 or less, and were cared for on a neurology, oncology, or pulmonology inpatient care unit. The research setting was the Samsung Medical Center in Seoul, South Korea. METHODS: Participants were divided into 2 groups: the experimental group were based on a VEFO on top of the standard hospital mattress used in our facility. Participants in the control group were placed on a standard hospital mattress with/without air overlay. All patients were given standard nursing care for prevention of PI. Skin assessments were completed daily over a period of 2 weeks. In addition, we compared IPs of the standard hospital mattress and the VEFO in participants randomly allocated to the intervention group. Interface pressure was measured over the sacral/coccygeal area with subjects in the supine position. Pressures were measured immediately before and immediately following placement of the VEFO and just before data collection began. Data were collected between October 2013 and November 2014. Pressure injury incidence was compared between groups using the χ test, and IPs were compared using the paired t test. INSTRUMENTS: Pressure injury development was determined using the staging system described in guidelines from the National Pressure Ulcer Advisory Panel, European Pressure Ulcer Advisory Panel, and Pan Pacific Pressure Injury Alliance in 2014. Interface pressure was measured using a device manufactured for this purpose. RESULTS: The incidence of PI development was significantly lower in subjects assigned to the experimental group as compared to those in the control group (3.6%-27.3% over the 2-week data collection period; P = .001). The maximum IP was significantly lower on the VEFO with standard hospital mattress than on the standard hospital mattress (paired t = 8.87, P < .001). CONCLUSIONS: Patients managed with a VEFO had a significantly lower incidence of PI than those managed with a standard hospital mattress. Additional research is needed to further characterize the efficacy of the VEFO, its effect on PI healing, and its effect of PI prevention in high-risk populations such as critically ill patients.

Hyaluronan in Medical Practice.

Hyaluronan is the major extracellular matrix glycosaminoglycan polymer present in vertebrate tissues, with a molar mass that can reach several megaDaltons. It is particularly prominent in the matrix of tissues undergoing rapid turnover, in fetal tissues, and wherever regeneration and repair are occurring. Hyaluronan has highly varied biological functions often dependent on molar mass, however they are highly dependent on source of hyaluronan, its purity and nature of contaminants. Hyaluronan of highmolar- mass is known for its anti-angiogenic, anti-inflammatory and immunosuppressive properties, unlike hyaluronan of low-molar-mass that has the opposite effects. Hyaluronan also has a broad range of clinical applications, such as intra-articular injection, in ophthalmology, otolaryngology, wound healing, and commercially in the cosmetic industry, as well as in drug delivery systems. Currently, polymers of hyaluronan are modified in order to improve their properties, including bioavailability and resistance to degradation. Because of greatly increased interest currently in hyaluronan, the multiple functions of the polymer are presented here, including medicine and industry, as well as recent progress in the formulation of hyaluronan-based materials.

Hemorragia masiva obstétrica: enfoque terapéutico actual / Massive obstetric hemorrhage: Current approach to management

La hemorragia masiva obstétrica es una de las causas principales de morbimortalidad materna en el mundo. Entre otras definiciones, se conoce como la pérdida > 2.500 ml de sangre y se asocia a ingreso en unidades de pacientes críticos y a histerectomía. Los cambios fisiológicos del embarazo permiten una hemorragia cuantiosa antes de objetivar una caída de la hemoglobina y/o el hematocrito. Dentro de los cambios fisiológicos del embarazo, existe una hipercoagulabilidad asociada a la gestante. Algunas comorbilidades asociadas al embarazo pueden contribuir a la aparición de una hemorragia catastrófica con una coagulopatía de consumo, que hace la situación aún más grave. La optimización, la preparación, el uso racional de recursos y la protocolización de actuaciones son útiles para mejorar los resultados en estas pacientes. El uso de protocolos basados en point of care con test viscoelásticos está demostrando utilidad. Si se produce una hipofibrinogenemia durante la hemorragia, la administración precoz de fibrinógeno puede ser muy útil. Para corregir eficazmente la coagulopatía pueden ser necesarios otros factores de la coagulación, además de fibrinógeno, durante la reposición en la hemorragia posparto. Se recomienda la realización de una histerectomía si las medidas médicas y quirúrgicas se han mostrado ineficaces

Massive obstetric hemorrhage is a major cause of maternal mortality and morbidity worldwide. It is defined (among others) as the loss of > 2,500 ml of blood, and is associated to a need for admission to critical care and/or hysterectomy. The relative hemodilution and high cardiac output found in normal pregnancy allows substantial bleeding before a drop in hemoglobin and/or hematocrit can be identified. Some comorbidities associated with pregnancy can contribute to the occurrence of catastrophic bleeding with consumption coagulopathy, which makes the situation even worse. Optimization, preparation, rational use of resources and protocolization of actions are often useful to improve outcomes in patients with postpartum hemorrhage. Using massive obstetric hemorrhage protocols is useful for facilitating rapid transfusion if needed, and can also be cost-effective. If hypofibrinogenemia during the bleeding episode is identified, early fibrinogen administration can be very useful. Other coagulation factors in addition to fibrinogen may be necessary during postpartum hemorrhage replacement measures in order to effectively correct coagulopathy. A hysterectomy is recommended if the medical and surgical measures prove ineffective

¿Son imprescindibles las pruebas viscoelásticas en la resucitación del paciente politraumático? / Are viscoelastic tests essential in polytrauma patient resuscitation?

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Prevention of pressure ulcers in the intensive care unit: a randomized trial of 2 viscoelastic foam support surfaces.

AIMS AND OBJECTIVES: The aim of this study is to compare whether differences exist between 2 viscoelastic foam support surfaces in the development of new pressure ulcers. BACKGROUND: There is evidence to support the use of viscoelastic foam over standard hospital foam to reduce pressure. A comparative effectiveness study was done to compare 2 viscoelastic foam support surfaces. DESIGN: A randomized controlled trial was carried out. METHOD: The study was performed in 2 intensive care units between October 1, 2008, and January 4, 2010. Patients (n = 105) admitted to intensive care unit were randomly assigned to viscoelastic foam 1 (n = 53) or viscoelastic foam 2 support surface (n = 52). RESULTS: In total, 42.8% of all patients developed a new pressure ulcer of stage 1 or worse. By stages, pressure ulcer incidence was 28.6%, 13.3%, and 1.0% for stages 1, 2, and 3, respectively. There was no significant difference in pressure ulcer incidence between the viscoelastic foam 1 and 2 groups (X2 = 0.07, df = 1, P > .05). CONCLUSIONS: No difference was found between 2 different viscoelastic foam surfaces in the prevention of pressure ulcers in patients treated in intensive care. RELEVANCE TO CLINICAL PRACTICE: Pressure ulcer incidence in critically ill patients remains high. Nurses must compare current products for effectiveness and develop innovative systems, processes, or devices to deliver best practices.

Diagnosis and deployment of a self-expanding foam for abdominal exsanguination: Translational questions for human use.

BACKGROUND: We have previously described the hemostatic efficacy of a self-expanding polyurethane foam in lethal venous and arterial hemorrhage models. A number of critical translational questions remain, including prehospital diagnosis of hemorrhage, use with diaphragmatic injury, effects on spontaneous respiration, the role of omentum, and presence of a laparotomy on foam properties. METHODS: In Experiment 1, diagnostic blood aspiration was attempted through a Veress needle before foam deployment during exsanguination (n = 53). In Experiment 2: a lethal hepatoportal injury/diaphragmatic laceration was created followed by foam (n = 6) or resuscitation (n = 10). In Experiment 3, the foam was deployed in naïve, spontaneously breathing animals (n = 7), and respiration was monitored. In Experiments 4 and 5, the foam was deployed above (n = 6) and below the omentum (n = 6) and in naïve animals (n = 6). Intra-abdominal pressure and organ contact were assessed. RESULTS: In Experiment 1, blood was successfully aspirated from a Veress needle in 70% of lethal iliac artery injuries and 100% of lethal hepatoportal injuries. In Experiment 2, in the presence of a diaphragm injury, between 0 cc and 110 cc of foam was found within the pleural space. Foam treatment resulted in a survival benefit relative to the control group at 1 hour (p = 0.03). In Experiment 3, hypercarbia was observed: mean (SD) Pco2 was 48 (9.4) mm Hg at baseline and 65 (14) mm Hg at 60 minutes. In Experiment 4, abdominal omentum seemed to influence organ contact and transport in two foam deployments. In Experiment 5, there was no difference in intra-abdominal pressure following foam deployment in the absence of a midline laparotomy. CONCLUSION: In a series of large animal studies, we addressed key translational issues surrounding safe use of foam treatment. These additional data, from diagnosis to deployment, will guide human experiences with foam treatment for massive abdominal exsanguination where no other treatments are available.

Self-expanding foam for prehospital treatment of severe intra-abdominal hemorrhage: dose finding study.

BACKGROUND: Noncompressible abdominal bleeding is a significant cause of preventable death on the battlefield and in the civilian trauma environment, with no effective therapies available at point of injury. We previously described the development of a percutaneously administered, self-expanding, poly(urea)urethane foam that improved survival in a lethal Grade V hepatic and portal vein injury model in swine. In this study, we hypothesized that survival with foam treatment is dose dependent. METHODS: A high-grade hepatoportal injury was created in a closed abdominal cavity, resulting in massive noncompressible hemorrhage. After injury, the animals were divided into five groups. The control group (n = 12) was treated only with fluid resuscitation, and four polymer groups received different dose volumes (Group 1, n = 6, 64 mL; Group 2, n = 6, 85 mL; Group 3, n = 18, 100 mL; and Group 4, n = 10, 120 mL) in addition to fluids. Ten minutes after injury, the foam was percutaneously administered, and animals were monitored for 3 hours. RESULTS: Survival with hepatoportal injury was highest in Group 4 (90%) and decreased in a dose-dependent fashion (Group 3, 72%; Group 2, 33%; Group 1, 17%). All polymer groups survived significantly longer than the controls (8.3%). Hemorrhage rate was reduced in all groups but lowest in Group 4 versus the control group (0.34 [0.052] vs. 3.0 [1.3] mL/kg/min, p < 0.001). Increasing foam dose volume was associated with increased peak intra-abdominal pressure (88.2 [38.9] in Group 4 vs. 9.5 [3.2] in the controls, p < 0.0001) and increased incidence of focal bowel injuries. CONCLUSION: The self-expanding foam significantly improves survival in a dose-dependent fashion in an otherwise lethal injury. Higher doses are associated with better survival but resulted in the need for bowel resection.