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Rajesh A, Schaefer RM, Krohmer JR, Bank EA, Holcomb JB, Jenkins DH. From shortages to solutions: Liquid plasma as a practical alternative to whole blood for prehospital trauma resuscitation. Transfusion 2025; 65 Suppl 1:S288-S296. [PMID: 40181605 DOI: 10.1111/trf.18183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 02/10/2025] [Accepted: 02/12/2025] [Indexed: 04/05/2025]
Abstract
Trauma-induced hemorrhagic shock remains a leading cause of preventable mortality, necessitating timely and effective resuscitation strategies. While low-titer O whole blood (LTOWB) is the preferred choice for prehospital resuscitation due to its balanced composition and ease of use, overall widespread implementation is hindered by persistent supply chain issues and daily logistical challenges of access and deployment. Platelets, containing plasma as a component, are considered the next best alternative to LTOWB but are constrained by their short shelf life and ongoing scarcity, and ongoing storage compliance, rendering their use impractical. This review evaluates plasma-based alternatives, particularly liquid plasma (LP), as a viable and cost-effective substitute therapeutic modality. LP offers a 26-day refrigerated shelf life compared to the 5-day limit of thawed fresh frozen plasma (FFP) and eliminates the challenges associated with freezing and thawing while maintaining clinical efficacy. Preliminary economic analyses further underscore the advantages of LP, demonstrating reduced wastage and lower costs compared to LTOWB, especially when partnering with a hospital system. Acknowledging the barriers in implementing prehospital blood transfusion programs due to blood supply and costs, we advocate for emergency medical service (EMS) adoption of LP, highlighting its availability, comparable efficacy to LTOWB, and cost-effectiveness. Until LTOWB becomes more accessible, LP should be prioritized in prehospital care to optimize outcomes for trauma patients in hemorrhagic shock.
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Affiliation(s)
- Aashish Rajesh
- Department of Surgery, UT Health San Antonio, San Antonio, Texas, USA
| | | | - Jon R Krohmer
- Department of Emergency Medicine, Western Michigan University, Kalamazoo, Michigan, USA
- Michigan State University, East Lansing, Michigan, USA
- EMSMD PLLC, Grandville, Michigan, USA
| | - Eric A Bank
- Harris County Emergency Services District 48, Katy, Texas, USA
| | - John B Holcomb
- Division of Trauma and Acute Care Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Donald H Jenkins
- Department of Surgery, UT Health San Antonio, San Antonio, Texas, USA
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Risinger WB, Matheson PJ, Franklin ME, Hammond VR, Lakshmanan J, Pushpakumar S, Li Y, Volk EE, Harbrecht BG, Smith JW. PLASMA UTILIZATION EXACERBATES RENAL CORTEX INFLAMMATION IN A RODENT MODEL OF HEMORRHAGIC SHOCK AND RESUSCITATION. Shock 2025; 63:796-803. [PMID: 39965637 DOI: 10.1097/shk.0000000000002563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/20/2025]
Abstract
ABSTRACT Background and Hypothesis: Resuscitation strategies incorporating fresh frozen plasma have become the standard of care in the management of traumatic hemorrhagic shock. While plasma resuscitation has been shown to augment the circulation and reduce inflammation within the splanchnic and pulmonary circulation, its global effect on the kidney remains unknown. We hypothesized that plasma would improve intrarenal blood flow and reduce parenchymal inflammation when compared to resuscitation with lactated ringer's. Methods: Animals were randomized into four groups (n = 8): a) baseline, b) hemorrhagic shock alone, c) lactated ringer's resuscitation, and d) fresh frozen plasma resuscitation. Multiplex immunoassays were used to evaluate cytokine and chemokine signaling within the renal cortex and immunohistochemistry was used to identify leukocyte infiltration. Doppler ultrasonography was used to evaluate changes in blood flow and maximum kidney diameter during hemorrhagic shock and resuscitation. Results: While no difference in resistive index (surrogate for blood flow) within the renal artery or parenchymal vessels was observed between resuscitation strategies, plasma resulted in increased transverse kidney diameter. Plasma administration promoted cytokine/chemokine signaling, resulting in increased infiltration of leukocytes within the renal cortex when compared to lactated ringer's. Conclusion: Although the clinical benefits of plasma resuscitation mandate its utilization, our current findings highlight the complexities of plasma resuscitation. While the increase in renal diameter may be related to augmentation of the microcirculation, plasma resuscitation did not enhance macro-circulatory blood flow. Furthermore, plasma resuscitation appears to exacerbate inflammation within the renal cortex after hemorrhage. The downstream physiologic implications of plasma-induced inflammation warrant further exploration.
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Affiliation(s)
- William B Risinger
- Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky
| | - Paul J Matheson
- Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky
| | - Marisa E Franklin
- Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky
| | - Victoria R Hammond
- Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky
| | - Jaganathan Lakshmanan
- Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky
| | - Sathnur Pushpakumar
- Department of Physiology, University of Louisville School of Medicine, Louisville, Kentucky
| | - Yan Li
- Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky
| | - Emily E Volk
- Department of Pathology and Laboratory Medicine, University of Louisville School of Medicine, Louisville, Kentucky
| | - Brian G Harbrecht
- Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky
| | - Jason W Smith
- Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky
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Kimura A, Suehiro K, Yamada T, Shinta Y, Juri T, Fujimoto Y, Hirano S, Mori T. Protective Effects of Hydrogen-Rich Saline Against Hemorrhagic Shock in Rats via an Endothelial Glycocalyx Pathway. Biomedicines 2025; 13:833. [PMID: 40299405 PMCID: PMC12024667 DOI: 10.3390/biomedicines13040833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 02/25/2025] [Accepted: 03/25/2025] [Indexed: 04/30/2025] Open
Abstract
Background/Objective: The endothelial glycocalyx is a gel-like layer on the vascular endothelial surface that is crucial for maintaining vascular homeostasis. Massive bleeding leads to the shedding of the glycocalyx, which can lead to vascular leakage during fluid administration. Recently, the beneficial effect of hydrogen inhalation in the treatment of hemorrhagic shock has been reported. However, the efficacy of hydrogen-rich saline in protecting the glycocalyx remains unclear. In this study, we investigated the effects of hydrogen-rich saline on glycocalyx degeneration. Methods: Rats under general anesthesia were divided into five groups: the sham, hemorrhagic shock, normal saline, colloid solution, and hydrogen-rich saline groups (n = 6 for each group). Blood was withdrawn, and blood pressure was maintained at 30-35 mmHg for 60 min. After inducing hemorrhagic shock in this way, each infusion product was administered intravenously to maintain blood pressure at 80 mmHg for 60 min. Glycocalyx thickness was assessed using the GlycoCheck system. Results: The use of hydrogen-rich saline significantly improved the survival rate (p < 0.05), and glycocalyx degeneration was significantly suppressed (p < 0.001), indicating the protective effect of hydrogen on the glycocalyx. Conclusion: Intravenous administration of hydrogen-rich saline in hemorrhagic shock attenuates glycocalyx degeneration compared to conventional fluid resuscitation, which can improve survival rates.
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Affiliation(s)
- Aya Kimura
- Department of Anesthesiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8586, Japan; (A.K.); (T.Y.); (Y.S.); (T.J.); (Y.F.); (T.M.)
| | - Koichi Suehiro
- Department of Anesthesiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8586, Japan; (A.K.); (T.Y.); (Y.S.); (T.J.); (Y.F.); (T.M.)
| | - Tokuhiro Yamada
- Department of Anesthesiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8586, Japan; (A.K.); (T.Y.); (Y.S.); (T.J.); (Y.F.); (T.M.)
| | - Yasuda Shinta
- Department of Anesthesiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8586, Japan; (A.K.); (T.Y.); (Y.S.); (T.J.); (Y.F.); (T.M.)
| | - Takashi Juri
- Department of Anesthesiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8586, Japan; (A.K.); (T.Y.); (Y.S.); (T.J.); (Y.F.); (T.M.)
| | - Yohei Fujimoto
- Department of Anesthesiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8586, Japan; (A.K.); (T.Y.); (Y.S.); (T.J.); (Y.F.); (T.M.)
| | - Shinichi Hirano
- Independent Researcher, 5-8-1-207 Honson, Shibasaki, Numazu 253-0042, Japan;
| | - Takashi Mori
- Department of Anesthesiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8586, Japan; (A.K.); (T.Y.); (Y.S.); (T.J.); (Y.F.); (T.M.)
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4
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Grottke O, Fries D. [Transfusion of Fresh Frozen Plasma and Coagulation Factors - Indications, Practice and Complications]. Anasthesiol Intensivmed Notfallmed Schmerzther 2025; 60:25-34. [PMID: 39778585 DOI: 10.1055/a-2234-4021] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
After severe trauma, but also perioperatively, massive bleeding is associated with increased morbidity and mortality. In severely injured patients, hemorrhagic shock remains to be the main cause of death in addition to traumatic brain hemorrhage. In non-cardiac surgery, a surgical bleeding complication increases perioperative morbidity (intensive care length of stay, acute renal failure, infections, thromboembolic complications) by a factor of three to four and mortality by a factor of six. In cardiac surgery, postoperative bleeding requiring surgical revision is associated with a 50% increase in mortality. One possible therapeutic approach is the transfusion of erythrocytes to plasma in a fixed ratio. This practice of untargeted coagulation therapy is mainly used in the USA and some Scandinavian countries. Mortality is significantly worse in the USA than in central Europe, particularly in the case of severe injuries. There is increasing evidence that targeted coagulation therapy with coagulation factor concentrates based on the results of point-of-care coagulation diagnostics is more effective and associated with fewer transfusion- and bleeding-related complications.
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Pinto DN, Mehta C, Kelly EJ, Mathew SK, Carney BC, McLawhorn MM, Moffatt LT, Travis TE, Shupp JW, Tejiram S. Plasma Inclusive Resuscitation Is Not Associated With Transfusion-Related Acute Lung Injury Under Updated Guidelines. J Surg Res 2024; 304:81-89. [PMID: 39536699 DOI: 10.1016/j.jss.2024.08.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 07/24/2024] [Accepted: 08/16/2024] [Indexed: 11/16/2024]
Abstract
INTRODUCTION Plasma inclusive resuscitation (PIR) uses fresh frozen plasma as an adjunct to crystalloid in the management of burn shock and has potential benefits over other colloids. Yet, safety concerns for transfusion-related acute lung injury (TRALI) exist. The aim of this study evaluated the association between TRALI and PIR in a cohort of severely burn-injured patients using the updated Canadian Blood Services Consensus definitions. METHODS Burn-injured patients requiring PIR at a burn center from 2018 to 2022 were retrospectively reviewed. To assess for TRALI, data related to acute hypoxemia, bilateral pulmonary edema, left atrial hypertension, and changes to respiratory status up to 6 h after PIR were recorded. To identify other risks and benefits associated with PIR timing, resuscitative volumes and outcomes were compared between early (0-8 h) and late PIR (8-24 h) initiation. RESULTS Of the 88 patients included for study, no patient developed TRALI type I or II under the updated definitions. Early (n = 39) compared to late PIR (n = 49) was associated with a higher percent total body surface area (TBSA, 36.3%, 26.0%, P = 0.01). The predicted 24-h volume was higher for early PIR (10.1 L, 6.3 L, P = 0.049), but the observed 24-h volume (cc/kg/%TBSA) was not significantly different (5.2, 5.3, P = 0.62). CONCLUSIONS In a cohort of severely burn-injured patients undergoing PIR, no patient developed TRALI type I or type II under the updated Canadian Blood Services Consensus definitions. Earlier use of PIR was not associated with higher resuscitative volumes despite higher TBSA. Further studies are necessary to better ascertain the potential risks and benefits associated with PIR.
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Affiliation(s)
- Desiree N Pinto
- Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia; Department of Surgery, Georgetown University School of Medicine, Washington, District of Columbia
| | - Caitlin Mehta
- Georgetown University School of Medicine, Washington, District of Columbia
| | - Edward J Kelly
- Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia
| | - Shane K Mathew
- Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia
| | - Bonnie C Carney
- Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, District of Columbia
| | - Melissa M McLawhorn
- Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia
| | - Lauren T Moffatt
- Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia; Department of Surgery, Georgetown University School of Medicine, Washington, District of Columbia; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, District of Columbia
| | - Taryn E Travis
- Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia; Department of Surgery, Georgetown University School of Medicine, Washington, District of Columbia; The Burn Center, Department of Surgery, MedStar Washington Hospital Center, Washington, District of Columbia; Department of Plastic and Reconstructive Surgery, Georgetown University School of Medicine, Washington, District of Columbia
| | - Jeffrey W Shupp
- Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia; Department of Surgery, Georgetown University School of Medicine, Washington, District of Columbia; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, District of Columbia; The Burn Center, Department of Surgery, MedStar Washington Hospital Center, Washington, District of Columbia; Department of Plastic and Reconstructive Surgery, Georgetown University School of Medicine, Washington, District of Columbia
| | - Shawn Tejiram
- Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia; Department of Surgery, Georgetown University School of Medicine, Washington, District of Columbia; The Burn Center, Department of Surgery, MedStar Washington Hospital Center, Washington, District of Columbia; Department of Plastic and Reconstructive Surgery, Georgetown University School of Medicine, Washington, District of Columbia.
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Lawrence-Mills S, Santoro F, Foster A, Talbot CT, Tinson E, Humm K. Retrospective evaluation of plasma transfusions in dogs undergoing general anaesthesia: 85 cases (2017-2021). Vet Anaesth Analg 2024; 51:594-602. [PMID: 39395873 DOI: 10.1016/j.vaa.2024.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 05/27/2024] [Accepted: 07/08/2024] [Indexed: 10/14/2024]
Abstract
OBJECTIVE To describe the use of plasma transfusion in anaesthetized dogs, specifically the triggers for use, the population administered plasma, reported adverse events and human errors associated with transfusion. STUDY DESIGN Retrospective observational study. ANIMALS A total of 85 client-owned dogs. METHODS A search of electronic transfusion and anaesthetic records at a university teaching hospital was performed to identify dogs administered plasma during the study period (January 2017 to June 2021). Data collected included signalment, surgical procedure, intraoperative triggers for transfusion, the type of plasma, rate of transfusion and the presence of transfusion reactions, human errors or deviation from transfusion guidelines. RESULTS During this period, 85 dogs were administered plasma. Sepsis was diagnosed in 49/85 (58%) dogs, with 42/85 (49%) animals undergoing surgery for septic peritonitis. Perianaesthetic hypotension contributed to the decision to administer plasma in 67/85 (79%) dogs. In 33/85 (39%) dogs, hypotension was the only reason for transfusion, while 31/85 (36%) had other influencing factors, most commonly hypoproteinaemia. Fresh frozen plasma was administered in 95% of cases. Only 31% of transfusions were started at a slower 'test dose' rate and 79% of dogs administered boluses of plasma. No definite, probable or possible transfusion reactions were identified using current veterinary guidelines. CONCLUSIONS AND CLINICAL RELEVANCE Plasma transfusions were commonly administered to dogs presenting with sepsis for haemodynamic optimization. Clinicians often chose to bolus plasma instead of initiating transfusions at the recommended initial slow starting rate. No transfusion reactions were identified; however, some reactions may have been masked by the effects of general anaesthesia and/or have been difficult to recognize in this critically ill canine population.
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Affiliation(s)
| | - Francesco Santoro
- Clinical Science and Services, The Royal Veterinary College, Radlett, UK
| | | | - Charles T Talbot
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA
| | - Erica Tinson
- Clinical Science and Services, The Royal Veterinary College, Radlett, UK
| | - Karen Humm
- Clinical Science and Services, The Royal Veterinary College, Radlett, UK
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Kemberi M, Minns AF, Santamaria S. Soluble Proteoglycans and Proteoglycan Fragments as Biomarkers of Pathological Extracellular Matrix Remodeling. PROTEOGLYCAN RESEARCH 2024; 2:e70011. [PMID: 39600538 PMCID: PMC11587194 DOI: 10.1002/pgr2.70011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 10/09/2024] [Accepted: 10/23/2024] [Indexed: 11/29/2024]
Abstract
Proteoglycans and their proteolytic fragments diffuse into biological fluids such as plasma, serum, urine, or synovial fluid, where they can be detected by antibodies or mass-spectrometry. Neopeptides generated by the proteolysis of proteoglycans are recognized by specific neoepitope antibodies and can act as a proxy for the activity of certain proteases. Proteoglycan and proteoglycan fragments can be potentially used as prognostic, diagnostic, or theragnostic biomarkers for several diseases characterized by dysregulated extracellular matrix remodeling such as osteoarthritis, rheumatoid arthritis, atherosclerosis, thoracic aortic aneurysms, central nervous system disorders, viral infections, and cancer. Here, we review the main mechanisms accounting for the presence of soluble proteoglycans and their fragments in biological fluids, their potential application as diagnostic, prognostic, or theragnostic biomarkers, and highlight challenges and opportunities ahead of their clinical translation.
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Affiliation(s)
- Marsioleda Kemberi
- Barts and the London School of Medicine and DentistryQueen Mary University of LondonLondonEnglandUK
| | - Alexander F. Minns
- Department of Biochemical SciencesSchool of Biosciences, Faculty of Health and Medical Sciences, University of SurreyGuildfordSurreyUK
| | - Salvatore Santamaria
- Department of Biochemical SciencesSchool of Biosciences, Faculty of Health and Medical Sciences, University of SurreyGuildfordSurreyUK
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Clausen NE, Meyhoff CS, Henriksen HH, Lindhardt A, Pott FC, Lunen TB, Gybel-Brask M, Lange T, Johansson PI, Stensballe J. Plasma as endothelial rescue in septic shock: A randomized, phase 2a pilot trial. Transfusion 2024; 64:1653-1661. [PMID: 38973502 DOI: 10.1111/trf.17939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 05/17/2024] [Accepted: 06/17/2024] [Indexed: 07/09/2024]
Abstract
BACKGROUND Septic shock is associated with high morbidity and mortality, the endothelium plays an important role. Crystalloids is standard of care to maintain intravascular volume. Plasma is associated with improved endothelial integrity and restoration of the glycocalyx layer. We evaluated the efficacy and safety aspects of cell-free and pathogen inactivated pooled plasma (OctaplasLG®) as resuscitation in septic shock patients. STUDY DESIGN AND METHODS This randomized, investigator-initiated phase IIa trial ran at a Danish single center intensive care unit, from 2017 to 2019. Patients were 18 years of age or older with septic shock and randomized to fluid optimization with OctaplasLG® or Ringer-acetate in the first 24 h. The primary endpoints were changes in biomarkers indicative of endothelial activation, damage, and microvascular perfusion from baseline to 24 h. Safety events and mortality were assessed during 90 days. RESULTS Forty-four patients were randomized, 20 to OctaplasLG versus 24 to Ringer-acetate. The median age was 69, and 55% were men. Median Sequential Organ Failure Assessment score was 13. Baseline differences favoring the Ringer-acetate group were observed. The OctaplasLG® group was resuscitated with 740 mL plasma and the Ringer-acetate group with 841 mL crystalloids. There was no significant change in the microvascular perfusion or five biomarkers except VEGFR1 change, which was higher in patients receiving OctaplasLG® 0.12(SD 0.37) versus Ringer-acetate -0.24 (SD 0.39), with mean difference 0.36 (95% CI, 0.13-0.59, p = .003) in favor of Ringer-acetate. DISCUSSION This study found that fluid resuscitation with OctaplasLG® in critically ill septic shock patients is feasible. Baseline confounding prevented assessment of the potential effect of OctaplasLG®.
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Affiliation(s)
- Niels E Clausen
- Department of Anesthesia and Intensive Care, Copenhagen University Hospital -Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Christian S Meyhoff
- Department of Anesthesia and Intensive Care, Copenhagen University Hospital -Bispebjerg and Frederiksberg, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Hanne H Henriksen
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Anne Lindhardt
- Department of Anesthesia and Intensive Care, Zealand University Hospital, Køge, Denmark
| | - Frank C Pott
- Department of Anesthesia and Intensive Care, Copenhagen University Hospital -Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Thomas Bech Lunen
- Department of Anesthesia and Intensive Care, Zealand University Hospital, Køge, Denmark
| | - Mikkel Gybel-Brask
- Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Theis Lange
- Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark
| | - Pär I Johansson
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Jakob Stensballe
- Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Department of Anesthesia and Trauma Center, Centre of Head and Orthopedics, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
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Kravitz MS, Kattouf N, Stewart IJ, Ginde AA, Schmidt EP, Shapiro NI. Plasma for prevention and treatment of glycocalyx degradation in trauma and sepsis. Crit Care 2024; 28:254. [PMID: 39033135 PMCID: PMC11265047 DOI: 10.1186/s13054-024-05026-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 07/06/2024] [Indexed: 07/23/2024] Open
Abstract
The endothelial glycocalyx, a gel-like layer that lines the luminal surface of blood vessels, is composed of proteoglycans, glycoproteins, and glycosaminoglycans. The endothelial glycocalyx plays an essential role in vascular homeostasis, and its degradation in trauma and sepsis can lead to microvascular dysfunction and organ injury. While there are no proven therapies for preventing or treating endothelial glycocalyx degradation, some initial literature suggests that plasma may have a therapeutic role in trauma and sepsis patients. Overall, the literature suggesting the use of plasma as a therapy for endothelial glycocalyx degradation is non-clinical basic science or exploratory. Plasma is an established therapy in the resuscitation of patients with hemorrhage for restoration of coagulation factors. However, plasma also contains other bioactive components, including sphingosine-1 phosphate, antithrombin, and adiponectin, which may protect and restore the endothelial glycocalyx, thereby helping to maintain or restore vascular homeostasis. This narrative review begins by describing the endothelial glycocalyx in health and disease: we discuss the overlapping disease mechanisms in trauma and sepsis that lead to its damage and introduce plasma transfusion as a potential therapy for prevention and treatment of endothelial glycocalyx degradation. Second, we review the literature on plasma as an exploratory therapy for endothelial glycocalyx degradation in trauma and sepsis. Third, we discuss the safety of plasma transfusion by reviewing the adverse events associated with plasma and other blood product transfusions, and we examine modern transfusion precautions that have enhanced the safety of plasma transfusion. We conclude that the literature proposes that plasma may have the potential to prevent and treat endothelial glycocalyx degradation in trauma and sepsis, indicating the need for further research.
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Affiliation(s)
- M S Kravitz
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
| | - N Kattouf
- Department of Emergency Medicine, Mount Sinai School of Medicine, New York, NY, USA
| | - I J Stewart
- Department of Medicine, Uniformed Services University, Bethesda, MD, USA
| | - A A Ginde
- Department of Emergency Medicine, University of Colorado School of Medicines, Aurora, CO, USA
| | - E P Schmidt
- Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - N I Shapiro
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
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10
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Racine-Brzostek SE, Cushing MM, Gareis M, Heger A, Mehta Shah T, Scully M. Thirty years of experience with solvent/detergent-treated plasma for transfusion medicine. Transfusion 2024; 64:1132-1153. [PMID: 38644541 DOI: 10.1111/trf.17836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 03/26/2024] [Accepted: 03/28/2024] [Indexed: 04/23/2024]
Affiliation(s)
| | - Melissa M Cushing
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
- Department of Anesthesiology, Weill Cornell Medicine, New York, New York, USA
| | - Michelle Gareis
- Octapharma Pharmazeutika Produktionsges.mb.H, Vienna, Austria
| | - Andrea Heger
- Octapharma Pharmazeutika Produktionsges.mb.H, Vienna, Austria
| | | | - Marie Scully
- Department of Haematology, University College London Hospital, London, UK
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11
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McMullan RR, McAuley DF, O'Kane CM, Silversides JA. Vascular leak in sepsis: physiological basis and potential therapeutic advances. Crit Care 2024; 28:97. [PMID: 38521954 PMCID: PMC10961003 DOI: 10.1186/s13054-024-04875-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 03/14/2024] [Indexed: 03/25/2024] Open
Abstract
Sepsis is a life-threatening condition characterised by endothelial barrier dysfunction and impairment of normal microcirculatory function, resulting in a state of hypoperfusion and tissue oedema. No specific pharmacological therapies are currently used to attenuate microvascular injury. Given the prominent role of endothelial breakdown and microcirculatory dysfunction in sepsis, there is a need for effective strategies to protect the endothelium. In this review we will discuss key mechanisms and putative therapeutic agents relevant to endothelial barrier function.
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Affiliation(s)
- Ross R McMullan
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast, Lisburn Road, Belfast, BT9 7BL, UK.
| | - Daniel F McAuley
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast, Lisburn Road, Belfast, BT9 7BL, UK
- Department of Critical Care, Belfast Health and Social Care Trust, Belfast, UK
| | - Cecilia M O'Kane
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast, Lisburn Road, Belfast, BT9 7BL, UK
| | - Jonathan A Silversides
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast, Lisburn Road, Belfast, BT9 7BL, UK
- Department of Critical Care, Belfast Health and Social Care Trust, Belfast, UK
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Wang G, Lian H, Zhang H, Wang X. Microcirculation and Mitochondria: The Critical Unit. J Clin Med 2023; 12:6453. [PMID: 37892591 PMCID: PMC10607663 DOI: 10.3390/jcm12206453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/22/2023] [Accepted: 10/08/2023] [Indexed: 10/29/2023] Open
Abstract
Critical illness is often accompanied by a hemodynamic imbalance between macrocirculation and microcirculation, as well as mitochondrial dysfunction. Microcirculatory disorders lead to abnormalities in the supply of oxygen to tissue cells, while mitochondrial dysfunction leads to abnormal energy metabolism and impaired tissue oxygen utilization, making these conditions important pathogenic factors of critical illness. At the same time, there is a close relationship between the microcirculation and mitochondria. We introduce here the concept of a "critical unit", with two core components: microcirculation, which mainly comprises the microvascular network and endothelial cells, especially the endothelial glycocalyx; and mitochondria, which are mainly involved in energy metabolism but perform other non-negligible functions. This review also introduces several techniques and devices that can be utilized for the real-time synchronous monitoring of the microcirculation and mitochondria, and thus critical unit monitoring. Finally, we put forward the concepts and strategies of critical unit-guided treatment.
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Affiliation(s)
- Guangjian Wang
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; (G.W.); (H.Z.)
| | - Hui Lian
- Department of Health Care, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China;
| | - Hongmin Zhang
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; (G.W.); (H.Z.)
| | - Xiaoting Wang
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; (G.W.); (H.Z.)
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13
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van den Brink DP, Kleinveld DJB, Bongers A, Vos J, Roelofs JJTH, Weber NC, van Buul JD, Juffermans NP. The effects of resuscitation with different plasma products on endothelial permeability and organ injury in a rat pneumosepsis model. Intensive Care Med Exp 2023; 11:62. [PMID: 37728777 PMCID: PMC10511387 DOI: 10.1186/s40635-023-00549-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 09/11/2023] [Indexed: 09/21/2023] Open
Abstract
BACKGROUND Endothelial injury and permeability are a hallmark of sepsis. Initial resuscitation of septic patients with crystalloids is associated with aggravation of endothelial permeability, which may be related either to low protein content or to volume. We investigated whether initial resuscitation with different types of plasma or albumin decreases endothelial dysfunction and organ injury in a pneumosepsis rat model compared to the same volume of crystalloids. STUDY DESIGN AND METHODS Sprague-Dawley rats were intratracheally inoculated with Streptococcus pneumoniae. Twenty-four hours after inoculation, animals were randomized to 2 control groups and 5 intervention groups (n = 11 per group) to receive resuscitation with a fixed volume (8 mL/kg for 1 h) of either Ringer's Lactate, 5% human albumin, fresh frozen plasma derived from syngeneic donor rats (rFFP), human-derived plasma (hFFP) or human-derived solvent detergent plasma (SDP). Controls were non-resuscitated (n = 11) and healthy animals. Animals were sacrificed 5 h after start of resuscitation (T = 5). Pulmonary FITC-dextran leakage as a reflection of endothelial permeability was used as the primary outcome. RESULTS Inoculation with S. Pneumoniae resulted in sepsis, increased median lactate levels (1.6-2.8 mM, p < 0.01), pulmonary FITC-dextran leakage (52-134 µg mL-1, p < 0.05) and lung injury scores (0.7-6.9, p < 0.001) compared to healthy controls. Compared to animals receiving no resuscitation, animals resuscitated with rFFP had reduced pulmonary FITC leakage (134 vs 58 µg/mL, p = 0.011). However, there were no differences in any other markers of organ or endothelial injury. Resuscitation using different human plasma products or 5% albumin showed no differences in any outcome. CONCLUSIONS Resuscitation with plasma did not reduce endothelial and organ injury when compared to an equal resuscitation volume of crystalloids. Rat-derived FFP may decrease pulmonary leakage induced by shock.
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Affiliation(s)
- Daan P van den Brink
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
- Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
| | - Derek J B Kleinveld
- Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Intensive Care Medicine, Erasmus MC, Erasmus University of Rotterdam, Rotterdam, The Netherlands
| | - Annabel Bongers
- Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jaël Vos
- Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Joris J T H Roelofs
- Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Cardiovascular Sciences, Amsterdam UMC, Amsterdam, The Netherlands
| | - Nina C Weber
- Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jaap D van Buul
- Molecular Cell Biology Lab at Department Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands
- Leeuwenhoek Centre for Advanced Microscopy (LCAM), Section Molecular Cytology at Swammerdam Institute for Life Sciences (SILS) at University of Amsterdam, Amsterdam, The Netherlands
| | - Nicole P Juffermans
- Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Intensive Care Medicine, OLVG Hospital, Amsterdam, The Netherlands
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14
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Zhang J, Zhu Y, Zhou Y, Gao F, Qiu X, Li J, Yuan H, Jin W, Lin W. Pediatric adenovirus pneumonia: clinical practice and current treatment. Front Med (Lausanne) 2023; 10:1207568. [PMID: 37476615 PMCID: PMC10354292 DOI: 10.3389/fmed.2023.1207568] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Accepted: 06/19/2023] [Indexed: 07/22/2023] Open
Abstract
Adenovirus pneumonia is common in pediatric upper respiratory tract infection, which is comparatively easy to develop into severe cases and has a high mortality rate with many influential sequelae. As for pathogenesis, adenoviruses can directly damage target cells and activate the immune response to varying degrees. Early clinical recognition depends on patients' symptoms and laboratory tests, including those under 2 years old, dyspnea with systemic toxic symptoms, atelectasis or emphysema in CT image, decreased leukocytes, and significantly increased C-reaction protein (CRP) and procalcitonin (PCT), indicating the possibility of severe cases. Until now, there is no specific drug for adenovirus pneumonia, so in clinical practice, current treatment comprises antiviral drugs, respiratory support and bronchoscopy, immunomodulatory therapy, and blood purification. Additionally, post-infectious bronchiolitis obliterans (PIBO), hemophagocytic syndrome, and death should be carefully noted. Independent risk factors associated with the development of PIBO are invasive mechanical ventilation, intravenous steroid use, duration of fever, and male gender. Meanwhile, hypoxemia, hypercapnia, invasive mechanical ventilation, and low serum albumin levels are related to death. Among these, viral load and serological identification are not only "gold standard" for adenovirus pneumonia, but are also related to the severity and prognosis. Here, we discuss the progress of pathogenesis, early recognition, therapy, and risk factors for poor outcomes regarding severe pediatric adenovirus pneumonia.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Wei Lin
- Department of Pediatrics, The Second School of Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
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15
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Matsumoto H, Annen S, Mukai N, Ohshita M, Murata S, Harima Y, Ogawa S, Okita M, Nakabayashi Y, Kikuchi S, Takeba J, Sato N. Circulating Syndecan-1 Levels Are Associated with Chronological Coagulofibrinolytic Responses and the Development of Disseminated Intravascular Coagulation (DIC) after Trauma: A Retrospective Observational Study. J Clin Med 2023; 12:4386. [PMID: 37445421 DOI: 10.3390/jcm12134386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 06/16/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
BACKGROUND The purpose of this study was to evaluate the association between endotheliopathy represented by high levels of circulating syndecan-1 (SDC-1) and coagulofibrinolytic responses due to trauma, which can lead to disseminated intravascular coagulation (DIC). METHODS We retrospectively evaluated 48 eligible trauma patients immediately admitted to our hospital and assessed SDC-1 and coagulofibrinolytic parameters for 7 days after admission. We compared the longitudinal changes of coagulofibrinolytic parameters and SDC-1 levels between two groups (high and low SDC-1) according to median SDC-1 value on admission. RESULTS The median circulating SDC-1 level was 99.6 (61.1-214.3) ng/mL on admission, and levels remained high until 7 days after admission. Coagulofibrinolytic responses assessed by biomarkers immediately after trauma were correlated with SDC-1 elevation (thrombin-antithrombin complex, TAT: r = 0.352, p = 0.001; antithrombin, AT: r = -0.301, p < 0.001; plasmin-α2-plasmin inhibitor complex, PIC: r = 0.503, p = 0.035; tissue plasminogen activator, tPA: r = 0.630, p < 0.001). Sustained SDC-1 elevation was associated with intense and prolonged coagulation activation, impairment of anticoagulation, and fibrinolytic activation followed by inhibition of fibrinolysis, which are the primary responses associated with development of DIC in the acute phase of trauma. Elevation of circulating SDC-1 level was also associated with consumption coagulopathy and the need for transfusion, which revealed a significant association between high SDC-1 levels and the development of DIC after trauma (area under the curve, AUC = 0.845, cut-off value = 130.38 ng/mL, p = 0.001). CONCLUSIONS High circulating levels of syndecan-1 were associated with intense and prolonged coagulation activation, impairment of anticoagulation, fibrinolytic activation, and consumption coagulopathy after trauma. Endotheliopathy represented by SDC-1 elevation was associated with trauma induced coagulopathy, which can lead to the development of DIC.
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Affiliation(s)
- Hironori Matsumoto
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan
| | - Suguru Annen
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan
| | - Naoki Mukai
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan
| | - Muneaki Ohshita
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan
| | - Satoru Murata
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan
| | - Yutaka Harima
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan
| | - Shirou Ogawa
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan
| | - Mitsuo Okita
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan
| | - Yuki Nakabayashi
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan
| | - Satoshi Kikuchi
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan
| | - Jun Takeba
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan
| | - Norio Sato
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan
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David S, Russell L, Castro P, van de Louw A, Zafrani L, Pirani T, Nielsen ND, Mariotte E, Ferreyro BL, Kielstein JT, Montini L, Brignier AC, Kochanek M, Cid J, Robba C, Martin-Loeches I, Ostermann M, Juffermans NP. Research priorities for therapeutic plasma exchange in critically ill patients. Intensive Care Med Exp 2023; 11:26. [PMID: 37150798 PMCID: PMC10164453 DOI: 10.1186/s40635-023-00510-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 04/10/2023] [Indexed: 05/09/2023] Open
Abstract
Therapeutic plasma exchange (TPE) is a therapeutic intervention that separates plasma from blood cells to remove pathological factors or to replenish deficient factors. The use of TPE is increasing over the last decades. However, despite a good theoretical rationale and biological plausibility for TPE as a therapy for numerous diseases or syndromes associated with critical illness, TPE in the intensive care unit (ICU) setting has not been studied extensively. A group of eighteen experts around the globe from different clinical backgrounds used a modified Delphi method to phrase key research questions related to "TPE in the critically ill patient". These questions focused on: (1) the pathophysiological role of the removal and replacement process, (2) optimal timing of treatment, (3) dosing and treatment regimes, (4) risk-benefit assumptions and (5) novel indications in need of exploration. For all five topics, the current understanding as well as gaps in knowledge and future directions were assessed. The content should stimulate future research in the field and novel clinical applications.
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Affiliation(s)
- Sascha David
- Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland.
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
| | - Lene Russell
- Department of Intensive Care, Copenhagen University Hospital Gentofte, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Pedro Castro
- Medical Intensive Care Unit, Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Andry van de Louw
- Medical Intensive Care Unit, Penn State Health Hershey Medical Center, Hershey, PA, USA
| | - Lara Zafrani
- Medical Intensive Care Unit, Saint-Louis Hospital, AP-HP, University of Paris Cité, Paris, France
| | - Tasneem Pirani
- King's College Hospital, General and Liver Intensive Care, London, UK
| | - Nathan D Nielsen
- Division of Pulmonary, Critical Care and Sleep Medicine & Section of Transfusion Medicine and Therapeutic Pathology, University of New Mexico School of Medicine, Albuquerque, USA
| | - Eric Mariotte
- Medical Intensive Care Unit, Saint-Louis Hospital, AP-HP, University of Paris Cité, Paris, France
| | - Bruno L Ferreyro
- Department of Medicine, Sinai Health System and University Health Network, Toronto, Canada
| | - Jan T Kielstein
- Medical Clinic V, Nephrology, Rheumatology, Blood Purification, Academic Teaching Hospital Braunschweig, Brunswick, Germany
| | - Luca Montini
- Department of Intensive Care Medicine and Anesthesiology, "Fondazione Policlinico Universitario Agostino Gemelli IRCCS" Università Cattolica del Sacro Cuore, Rome, Italy
| | - Anne C Brignier
- Apheresis Unit, Saint-Louis Hospital, AP-HP, University of Paris Cite, Paris, France
| | - Matthias Kochanek
- Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO), University of Cologne, Cologne, Germany
| | - Joan Cid
- Apheresis and Cellular Therapy Unit, Department of Hemotherapy and Hemostasis, ICMHO, Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Chiara Robba
- IRCCS per Oncologia e Neuroscienze, Genoa, Italy
- Dipartimento di Scienze Chirurgiche Diagnostiche ed Integrate, Universita' di Genova, Genoa, Italy
| | - Ignacio Martin-Loeches
- Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James's Hospital, Dublin, D08 NHY1, Ireland
- Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, D02 PN91, Ireland
- Institut D'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Universidad de Barcelona, Ciberes, Barcelona, Spain
| | - Marlies Ostermann
- Department of Intensive Care, Guy's & St Thomas' Hospital, King's College London, London, UK
| | - Nicole P Juffermans
- Department of Intensive Care, OLVG Hospital, Amsterdam, The Netherlands
- Laboratory of Translational Intensive Care, Erasmus MC, Rotterdam, The Netherlands
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17
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Vyas A, Isaac S, Kaur D, Yadav U. Role of the PLASMIC Score in the Management of Thrombotic Thrombocytopenic Purpura. Cureus 2023; 15:e36188. [PMID: 37065284 PMCID: PMC10104422 DOI: 10.7759/cureus.36188] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/12/2023] [Indexed: 03/17/2023] Open
Abstract
We report the case of a middle-aged male presenting with fatigue and abdominal pain. Prompt investigations demonstrated microangiopathic hemolytic anemia and thrombocytopenia on a peripheral blood smear. Thrombotic thrombocytopenic purpura was suspected based on the PLASMIC score. The patient significantly improved with therapeutic plasma exchange and prednisone within the next few days. The disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 levels reduction is a definitive hallmark leading to microvascular thrombosis. However, some medical centers in the United States do not promptly have quick allowance to the levels. Hence, the PLASMIC score becomes imminent in initiating immediate management and preventing life-threatening complications.
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18
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Tucker H, Brohi K, Tan J, Aylwin C, Bloomer R, Cardigan R, Davenport R, Davies ED, Godfrey P, Hawes R, Lyon R, McCullagh J, Stanworth S, Thompson J, Uprichard J, Walsh S, Weaver A, Green L. Association of red blood cells and plasma transfusion versus red blood cell transfusion only with survival for treatment of major traumatic hemorrhage in prehospital setting in England: a multicenter study. Crit Care 2023; 27:25. [PMID: 36650557 PMCID: PMC9847037 DOI: 10.1186/s13054-022-04279-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 12/14/2022] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND In-hospital acute resuscitation in trauma has evolved toward early and balanced transfusion resuscitation with red blood cells (RBC) and plasma being transfused in equal ratios. Being able to deliver this ratio in prehospital environments is a challenge. A combined component, like leukocyte-depleted red cell and plasma (RCP), could facilitate early prehospital resuscitation with RBC and plasma, while at the same time improving logistics for the team. However, there is limited evidence on the clinical benefits of RCP. OBJECTIVE To compare prehospital transfusion of combined RCP versus RBC alone or RBC and plasma separately (RBC + P) on mortality in trauma bleeding patients. METHODS Data were collected prospectively on patients who received prehospital transfusion (RBC + thawed plasma/Lyoplas or RCP) for traumatic hemorrhage from six prehospital services in England (2018-2020). Retrospective data on patients who transfused RBC from 2015 to 2018 were included for comparison. The association between transfusion arms and 24-h and 30-day mortality, adjusting for age, injury mechanism, age, prehospital heart rate and blood pressure, was evaluated using generalized estimating equations. RESULTS Out of 970 recruited patients, 909 fulfilled the study criteria (RBC + P = 391, RCP = 295, RBC = 223). RBC + P patients were older (mean age 42 vs 35 years for RCP and RBC), and 80% had a blunt injury (RCP = 52%, RBC = 56%). RCP and RBC + P were associated with lower odds of death at 24-h, compared to RBC alone (adjusted odds ratio [aOR] 0.69 [95%CI: 0.52; 0.92] and 0.60 [95%CI: 0.32; 1.13], respectively). The lower odds of death for RBC + P and RCP vs RBC were driven by penetrating injury (aOR 0.22 [95%CI: 0.10; 0.53] and 0.39 [95%CI: 0.20; 0.76], respectively). There was no association between RCP or RBC + P with 30-day survival vs RBC. CONCLUSION Prehospital plasma transfusion for penetrating injury was associated with lower odds of death at 24-h compared to RBC alone. Large trials are needed to confirm these findings.
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Affiliation(s)
- Harriet Tucker
- grid.4868.20000 0001 2171 1133Centre for Trauma Sciences, Blizard Institute, Queen Mary University of London, 4 Newark Street, London, E1 2AT UK
| | - Karim Brohi
- grid.4868.20000 0001 2171 1133Centre for Trauma Sciences, Blizard Institute, Queen Mary University of London, 4 Newark Street, London, E1 2AT UK ,grid.139534.90000 0001 0372 5777Barts Health NHS Trust, London, UK
| | - Joachim Tan
- grid.264200.20000 0000 8546 682XSt George’s University of London, London, UK
| | - Christopher Aylwin
- grid.426467.50000 0001 2108 8951St Mary’s Hospital, Imperial College NHS Foundation Trust, London, UK
| | - Roger Bloomer
- grid.429705.d0000 0004 0489 4320Kings College Hospital NHS Foundation Trust, London, UK
| | - Rebecca Cardigan
- grid.436365.10000 0000 8685 6563NHS Blood and Transplant, Cambridge, UK
| | - Ross Davenport
- grid.4868.20000 0001 2171 1133Centre for Trauma Sciences, Blizard Institute, Queen Mary University of London, 4 Newark Street, London, E1 2AT UK ,grid.139534.90000 0001 0372 5777Barts Health NHS Trust, London, UK
| | - Edward D. Davies
- grid.416204.50000 0004 0391 9602Royal Preston Hospital, Preston, UK
| | - Phillip Godfrey
- grid.411812.f0000 0004 0400 2812James Cook University Hospital, Middlesbrough, UK
| | - Rachel Hawes
- Newcastle Upon Tyne NHS Foundation Trust, Newcastle, UK ,Great North Air Ambulance, Stockton-on-Tees, UK
| | | | | | - Simon Stanworth
- grid.436365.10000 0000 8685 6563NHS Blood and Transplant, Cambridge, UK ,grid.4991.50000 0004 1936 8948Oxford University Hospital NHS Foundation Trust, Oxford, UK
| | - Julian Thompson
- grid.416201.00000 0004 0417 1173Southmead Hospital, Bristol, UK ,Great West Air Ambulance, Bristol, UK
| | - James Uprichard
- grid.264200.20000 0000 8546 682XSt George’s University Hospital NHS Foundation Trust, London, UK
| | - Simon Walsh
- grid.426467.50000 0001 2108 8951St Mary’s Hospital, Imperial College NHS Foundation Trust, London, UK ,Essex and Hertfordshire Air Ambulance Trust, Essex, UK
| | - Anne Weaver
- grid.139534.90000 0001 0372 5777Barts Health NHS Trust, London, UK
| | - Laura Green
- grid.4868.20000 0001 2171 1133Centre for Trauma Sciences, Blizard Institute, Queen Mary University of London, 4 Newark Street, London, E1 2AT UK ,grid.139534.90000 0001 0372 5777Barts Health NHS Trust, London, UK ,grid.436365.10000 0000 8685 6563NHS Blood and Transplant, Cambridge, UK
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19
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The effects of female sexual hormones on the endothelial glycocalyx. CURRENT TOPICS IN MEMBRANES 2023; 91:89-137. [PMID: 37080682 DOI: 10.1016/bs.ctm.2023.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/12/2023]
Abstract
The glycocalyx is a layer composed of carbohydrate side chains bound to core proteins that lines the vascular endothelium. The integrity of the glycocalyx is essential for endothelial cells' performance and vascular homeostasis. The neuroendocrine and immune systems influence the composition, maintenance, activity and degradation of the endothelial glycocalyx. The female organism has unique characteristics, and estrogen and progesterone, the main female hormones are essential to the development and physiology of the reproductive system and to the ability to develop a fetus. Female sex hormones also exert a wide variety of effects on other organs, including the vascular endothelium. They upregulate nitric oxide synthase expression and activity, decrease oxidative stress, increase vasodilation, and protect from vascular injury. This review will discuss how female hormones and pregnancy, which prompts to high levels of estrogen and progesterone, modulate the endothelial glycocalyx. Diseases prevalent in women that alter the glycocalyx, and therapeutic forms to prevent glycocalyx degradation and potential treatments that can reconstitute its structure and function will also be discussed.
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20
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Cusack R, Leone M, Rodriguez AH, Martin-Loeches I. Endothelial Damage and the Microcirculation in Critical Illness. Biomedicines 2022; 10:biomedicines10123150. [PMID: 36551905 PMCID: PMC9776078 DOI: 10.3390/biomedicines10123150] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 11/22/2022] [Accepted: 11/28/2022] [Indexed: 12/12/2022] Open
Abstract
Endothelial integrity maintains microcirculatory flow and tissue oxygen delivery. The endothelial glycocalyx is involved in cell signalling, coagulation and inflammation. Our ability to treat critically ill and septic patients effectively is determined by understanding the underpinning biological mechanisms. Many mechanisms govern the development of sepsis and many large trials for new treatments have failed to show a benefit. Endothelial dysfunction is possibly one of these biological mechanisms. Glycocalyx damage is measured biochemically. Novel microscopy techniques now mean the glycocalyx can be indirectly visualised, using sidestream dark field imaging. How the clinical visualisation of microcirculation changes relate to biochemical laboratory measurements of glycocalyx damage is not clear. This article reviews the evidence for a relationship between clinically evaluable microcirculation and biological signal of glycocalyx disruption in various diseases in ICU. Microcirculation changes relate to biochemical evidence of glycocalyx damage in some disease states, but results are highly variable. Better understanding and larger studies of this relationship could improve phenotyping and personalised medicine in the future. Damage to the glycocalyx could underpin many critical illness pathologies and having real-time information on the glycocalyx and microcirculation in the future could improve patient stratification, diagnosis and treatment.
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Affiliation(s)
- Rachael Cusack
- Department of Intensive Care Medicine, St. James’s Hospital, James’s Street, D08 NHY1 Dublin, Ireland
- School of Medicine, Trinity College Dublin, College Green, D02 R590 Dublin, Ireland
| | - Marc Leone
- Department of Anaesthesiology and Intensive Care Unit, Hospital Nord, Assistance Publique Hôpitaux de Marseille, Aix Marseille University, 13015 Marseille, France
| | - Alejandro H. Rodriguez
- Intensive Care Unit, Hospital Universitario Joan XXIII, 43005 Tarragona, Spain
- Institut d’Investigació Sanitària Pere Virgil, 43007 Tarragona, Spain
- Departament Medicina I Cirurgia, Universitat Rovira i Virgili, 43003 Tarragona, Spain
- Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Ignacio Martin-Loeches
- Department of Intensive Care Medicine, St. James’s Hospital, James’s Street, D08 NHY1 Dublin, Ireland
- School of Medicine, Trinity College Dublin, College Green, D02 R590 Dublin, Ireland
- Correspondence:
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21
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YILDIZ GÖ, SERTCAKACİLAR G, AKYOL D, KARAKAŞ S, HERGÜNSEL GO. Malign asitli over kanserinde sitoredüktif cerrahide perioperatif hemodinamik optimizasyon. CUKUROVA MEDICAL JOURNAL 2022. [DOI: 10.17826/cumj.1097476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Purpose: In this study, we aimed to evaluate the effects of norepinephrine and albumin use in patients with epithelial ovarian cancer with malignant ascite in order to maintain plasma oncotic pressure and intravascular volume, to provide perioperative hemodynamic stabilization and tissue perfusion. In addition, it was aimed to compare in terms of postoperative intensive care admission, hospital stay and complications.
Materials and Methods: A total of 66 patients, 38 with ascites and 28 without ascites, who underwent cytoreductive surgery for ovarian cancer were included in this study. PVI and invasive arterial monitoring of the patients were performed after hemodynamic stabilization (after the start of surgery) (T0). T0, 1st hour (T1) and 2nd hour (T2) and postoperative (Tpostop.) Ascites patients were composed of 3 subgroups which the ones received norepinephrine (NE) infusion, norepinephrine + albumin (NEA) infusion or only fluid therapy (FT). From the perioperative hemodynamic and laboratory data of the patients, tissue perfusion was evaluated with lactate, and hemodynamic status was evaluated with pleth variability index (PVI), perfusion index (PI) and mean arterial pressure (MAP).
Results: Demographic and clinical findings did not differ significantly between patients with and without ascites. Lactate level in NEA / NE group in Tpostop, PVI level in T1h, T2h and Tpostop time frames were determined higher than the FT group. PI was found to be significantly lower in the T2 time frame. The postoperative ICU admission rate was higher in the NEA and NE groups. The duration of ICU stay in group NEA was shorter than in group NE.
Conclusion: We recommend the use of low-dose NE with albumin to provide perioperative hemodynamic optimization, tissue perfusion and plasma oncotic pressure in surgery of ovarian cancer with malignant ascites. Despite high fluid replacement in these patients, the use of norepinephrine and albumin together may have an important role in preventing / reducing major complications in the perioperative period.
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Affiliation(s)
- Güneş Özlem YILDIZ
- Department of Anesthesiology and Intensive Care, University of Health Sciences Istanbul, Bakirkoy Dr. Sadi Konuk Training and Research Hospital
| | - Gokhan SERTCAKACİLAR
- UNIVERSITY OF HEALTH SCIENCES, İSTANBUL BAKIRKÖY DR. SADİ KONUK TRAINING RESEARCH CENTER
| | - Duygu AKYOL
- SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İSTANBUL BAŞAKŞEHİR ÇAM VE SAKURA ŞEHİR SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ
| | - Sema KARAKAŞ
- UNIVERSITY OF HEALTH SCIENCES, İSTANBUL BAKIRKÖY DR. SADİ KONUK TRAINING RESEARCH CENTER
| | - Gülsüm Oya HERGÜNSEL
- UNIVERSITY OF HEALTH SCIENCES, İSTANBUL BAKIRKÖY DR. SADİ KONUK TRAINING RESEARCH CENTER
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22
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Biomarkers for the Prediction and Judgement of Sepsis and Sepsis Complications: A Step towards precision medicine? J Clin Med 2022; 11:jcm11195782. [PMID: 36233650 PMCID: PMC9571838 DOI: 10.3390/jcm11195782] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 09/19/2022] [Accepted: 09/25/2022] [Indexed: 11/16/2022] Open
Abstract
Sepsis and septic shock are a major public health concern and are still associated with high rates of morbidity and mortality. Whilst there is growing understanding of different phenotypes and endotypes of sepsis, all too often treatment strategies still only employ a “one-size-fits-all” approach. Biomarkers offer a unique opportunity to close this gap to more precise treatment approaches by providing insight into clinically hidden, yet complex, pathophysiology, or by individualizing treatment pathways. Predicting and evaluating systemic inflammation, sepsis or septic shock are essential to improve outcomes for these patients. Besides opportunities to improve patient care, employing biomarkers offers a unique opportunity to improve clinical research in patients with sepsis. The high rate of negative clinical trials in this field may partly be explained by a high degree of heterogeneity in patient cohorts and a lack of understanding of specific endotypes or phenotypes. Moving forward, biomarkers can support the selection of more homogeneous cohorts, thereby potentially improving study conditions of clinical trials. This may finally pave the way to a precision medicine approach to sepsis, septic shock and complication of sepsis in the future.
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23
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Bajpai M, Maheshwari A, Kumar S, Chhabra K, Kale P, Narayanan A, Gupta A, Gupta E, Trehanpati N, Agarwal R, Gupta K, Bhardwaj A, Islam M, Singh R, Yadav P, Kumar G, Sarin SK. Comparison of safety and efficacy of convalescent plasma with fresh frozen plasma in severe covid-19 patients. AN ACAD BRAS CIENC 2022; 94:e20210202. [PMID: 36102392 DOI: 10.1590/0001-3765202220210202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 04/07/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Role of Convalescent plasma (COPLA) to treat severe COVID-19 is under investigation. We compared efficacy and safety of COPLA with fresh frozen plasma (FFP) in severe COVID-19 patients. METHODS One group received COPLA with standard medical care (n = 14), and another group received random donor FFP, as control with standard medical care (n = 15) in severe COVID-19 disease. RESULTS The proportion of patients free of ventilation at day seven were 78.5% in COPLA group, and 93.3 % in control group were not significant (p= 0.258). However, improved respiratory rate, O2 saturation, SOFA score, and Ct value were observed in the COPLA group. No serious adverse events were noticed by plasma transfusion in both groups.
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Affiliation(s)
- Meenu Bajpai
- Institute of Liver and Biliary Sciences, Department of Transfusion Medicine, D1 ilbs, D-1, Vasant Kunj Rd, Ghitorni, 110070 New Delhi, Delhi, India
| | - Ashish Maheshwari
- Institute of Liver and Biliary Sciences, Department of Transfusion Medicine, D1 ilbs, D-1, Vasant Kunj Rd, Ghitorni, 110070 New Delhi, Delhi, India
| | - Suresh Kumar
- Lok Nayak Jai Prakash Hospital, Department of Medicine, J6QP+PRR, Jawaharlal Nehru Marg, Maulana Azad Medical College Campus, Delhi Gate, 110002 New Delhi, Delhi, India
| | - Karan Chhabra
- Lok Nayak Jai Prakash Hospital, Department of Medicine, J6QP+PRR, Jawaharlal Nehru Marg, Maulana Azad Medical College Campus, Delhi Gate, 110002 New Delhi, Delhi, India
| | - Pratibha Kale
- Institute of Liver and Biliary Sciences, Department of Microbiology, D1 ilbs, D-1, Vasant Kunj Rd, Ghitorni, 110070 New Delhi, Delhi, India
| | - Ashad Narayanan
- Institute of Liver and Biliary Sciences, Department of Hepatology, D1 ilbs, D-1, Vasant Kunj Rd, Ghitorni, 110070 New Delhi, Delhi, India
| | - Amita Gupta
- Institute of Liver and Biliary Sciences, Department of Transfusion Medicine, D1 ilbs, D-1, Vasant Kunj Rd, Ghitorni, 110070 New Delhi, Delhi, India
| | - Ekta Gupta
- Institute of Liver and Biliary Sciences, Department of Molecular and Cellular Medicine, D1 ilbs, D-1, Vasant Kunj Rd, Ghitorni, 110070 New Delhi, Delhi, India
| | - Nirupama Trehanpati
- Institute of Liver and Biliary Sciences, Department of Molecular and Cellular Medicine, D1 ilbs, D-1, Vasant Kunj Rd, Ghitorni, 110070 New Delhi, Delhi, India
| | - Reshu Agarwal
- Institute of Liver and Biliary Sciences,Department of HepatoVirology, D1 ilbs, D-1, Vasant Kunj Rd, Ghitorni, 110070 New Delhi, Delhi, India
| | - Kamini Gupta
- Institute of Liver and Biliary Sciences,Department of HepatoVirology, D1 ilbs, D-1, Vasant Kunj Rd, Ghitorni, 110070 New Delhi, Delhi, India
| | - Ankit Bhardwaj
- Institute of Liver and Biliary Sciences, Department of Clinical Research, D1 ilbs, D-1, Vasant Kunj Rd, Ghitorni, 110070 New Delhi, Delhi, India
| | - Mojahidul Islam
- Institute of Liver and Biliary Sciences, Department of Molecular and Cellular Medicine, D1 ilbs, D-1, Vasant Kunj Rd, Ghitorni, 110070 New Delhi, Delhi, India
| | - Ravinder Singh
- Institute of Liver and Biliary Sciences, Department of Molecular and Cellular Medicine, D1 ilbs, D-1, Vasant Kunj Rd, Ghitorni, 110070 New Delhi, Delhi, India
| | - Pushpa Yadav
- Institute of Liver and Biliary Sciences, Department of Molecular and Cellular Medicine, D1 ilbs, D-1, Vasant Kunj Rd, Ghitorni, 110070 New Delhi, Delhi, India
| | - Guresh Kumar
- Institute of Liver and Biliary Sciences, Department of Research, D1 ilbs, D-1, Vasant Kunj Rd, Ghitorni, 110070 New Delhi, Delhi, India
| | - Shiv K Sarin
- Institute of Liver and Biliary Sciences, Department of Hepatology, D1 ilbs, D-1, Vasant Kunj Rd, Ghitorni, 110070 New Delhi, Delhi, India
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24
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Milford EM, Meital L, Kuballa A, Reade MC, Russell FD. Fingolimod does not prevent syndecan-4 shedding from the endothelial glycocalyx in a cultured human umbilical vein endothelial cell model of vascular injury. Intensive Care Med Exp 2022; 10:34. [PMID: 35980492 PMCID: PMC9388705 DOI: 10.1186/s40635-022-00462-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 08/10/2022] [Indexed: 11/27/2022] Open
Abstract
Background Shedding of the endothelial glycocalyx (EG) is associated with poor outcomes in a range of conditions including sepsis. Fresh frozen plasma (FFP) restores the damaged EG to baseline thickness, however the mechanism for this effect is unknown, and some components of FFP have adverse effects unrelated to the EG. There is some limited evidence that sphingosine-1-phosphate (S1P) within FFP restores the EG by activating the endothelial cell S1P receptor 1 (S1PR1). However, there are disadvantages to using S1P clinically as an EG restorative therapy. A potential alternative is the S1PR agonist fingolimod (FTY720). The aim of this study was to assess whether FTY720 prevents EG shedding in injured cultured human umbilical vein endothelial cells. Methods Shedding of the EG was induced in cultured human umbilical vein endothelial cells (HUVECs) by exposure to adrenaline, TNF-α and H2O2. The cells were then assigned to one of six conditions for 4 h: uninjured and untreated, injured and untreated, injured and treated with FTY720 with and without the S1PR1 inhibitor W146, and injured and treated with 25% FFP with and without W146. Syndecan-4, a component of the EG, was measured in cell supernatants, and syndecan-4 and thrombomodulin mRNA expression was quantitated in cell lysates. Results The injury resulted in a 2.1-fold increase in syndecan-4 (p < 0.001), consistent with EG shedding. Syndecan-4 and thrombomodulin mRNA expression was increased (p < 0.001) and decreased (p < 0.05), respectively, by the injury. Syndecan-4 shedding was not affected by treatment with FTY720, whereas FFP attenuated syndecan-4 shedding back to baseline levels in the injured cells and this was unaffected by W146. Neither treatment affected syndecan-4 or thrombomodulin mRNA expression. Conclusions FTY720 did not prevent syndecan-4 shedding from the EG in the HUVEC model of endothelial injury, suggesting that activation of S1PR does not prevent EG damage. FFP prevented syndecan-4 shedding from the EG via a mechanism that was independent of S1PR1 and upregulation of SDC-4 production. Further studies to examine whether FTY720 or another S1PR agonist might have EG-protective effects under different conditions are warranted, as are investigations seeking the mechanism of EG protection conferred by FFP in this experimental model.
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Affiliation(s)
- Elissa M Milford
- Faculty of Medicine, University of Queensland, Herston, QLD, Australia. .,Intensive Care Unit, Royal Brisbane and Women's Hospital, Butterfield St., Herston, QLD, Australia.
| | - Lara Meital
- School of Health and Behavioural Sciences, University of the Sunshine Coast, Maroochydore, QLD, Australia.,Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD, Australia
| | - Anna Kuballa
- School of Health and Behavioural Sciences, University of the Sunshine Coast, Maroochydore, QLD, Australia.,Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD, Australia
| | - Michael C Reade
- Faculty of Medicine, University of Queensland, Herston, QLD, Australia.,Intensive Care Unit, Royal Brisbane and Women's Hospital, Butterfield St., Herston, QLD, Australia.,Joint Health Command, Australian Defence Force, Canberra, ACT, Australia
| | - Fraser D Russell
- School of Health and Behavioural Sciences, University of the Sunshine Coast, Maroochydore, QLD, Australia.,Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD, Australia
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25
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Dietrich M, Hölle T, Lalev LD, Loos M, Schmitt FCF, Fiedler MO, Hackert T, Richter DC, Weigand MA, Fischer D. Plasma Transfusion in Septic Shock—A Secondary Analysis of a Retrospective Single-Center Cohort. J Clin Med 2022; 11:jcm11154367. [PMID: 35955987 PMCID: PMC9369152 DOI: 10.3390/jcm11154367] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 07/09/2022] [Accepted: 07/22/2022] [Indexed: 11/16/2022] Open
Abstract
In sepsis, both beneficial and detrimental effects of fresh frozen plasma (FFP) transfusion have been reported. The aim of this study was to analyze the indication for and effect of FFP transfusion in patients with septic shock. We performed a secondary analysis of a retrospective single-center cohort of all patients treated for septic shock at the interdisciplinary surgical intensive care unit (ICU) of the Heidelberg University Hospital. Septic shock was defined according to sepsis-3 criteria. To assess the effects of FFP administration in the early phase of septic shock, we compared patients with and without FFP transfusion during the first 48 h of septic shock. Patients who died during the first 48 h of septic shock were excluded from the analysis. Primary endpoints were 30- and 90-day mortality. A total of 261 patients were identified, of which 100 (38.3%) received FFP transfusion within the first 48 h after septic shock onset. The unmatched analysis showed a trend toward higher 30- and 90-d mortality in the FFP group (30 d: +7% p = 0.261; 90 d: +11.9% p = 0.061). In the propensity-matched analysis, 30- and 90-day mortality were similar between groups. Plasma administration did not influence fluid or vasopressor need, lactate levels, ICU stay, or days on a ventilator. We found no significant harm or associated benefit of FFP use in the early phase of septic shock. Finally, plasma should only be used in patients with a strong indication according to current recommendations, as a conclusive evaluation of the risk-benefit ratio for plasma transfusion in septic shock cannot be made based on the current data.
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Affiliation(s)
- Maximilian Dietrich
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (T.H.); (L.D.L.); (F.C.F.S.); (M.O.F.); (D.C.R.); (M.A.W.); (D.F.)
- Correspondence:
| | - Tobias Hölle
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (T.H.); (L.D.L.); (F.C.F.S.); (M.O.F.); (D.C.R.); (M.A.W.); (D.F.)
| | - Lazar Detelinov Lalev
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (T.H.); (L.D.L.); (F.C.F.S.); (M.O.F.); (D.C.R.); (M.A.W.); (D.F.)
| | - Martin Loos
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (M.L.); (T.H.)
| | - Felix Carl Fabian Schmitt
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (T.H.); (L.D.L.); (F.C.F.S.); (M.O.F.); (D.C.R.); (M.A.W.); (D.F.)
| | - Mascha Onida Fiedler
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (T.H.); (L.D.L.); (F.C.F.S.); (M.O.F.); (D.C.R.); (M.A.W.); (D.F.)
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (M.L.); (T.H.)
| | - Daniel Christoph Richter
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (T.H.); (L.D.L.); (F.C.F.S.); (M.O.F.); (D.C.R.); (M.A.W.); (D.F.)
| | - Markus Alexander Weigand
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (T.H.); (L.D.L.); (F.C.F.S.); (M.O.F.); (D.C.R.); (M.A.W.); (D.F.)
| | - Dania Fischer
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (T.H.); (L.D.L.); (F.C.F.S.); (M.O.F.); (D.C.R.); (M.A.W.); (D.F.)
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26
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Patterson EK, Cepinskas G, Fraser DD. Endothelial Glycocalyx Degradation in Critical Illness and Injury. Front Med (Lausanne) 2022; 9:898592. [PMID: 35872762 PMCID: PMC9304628 DOI: 10.3389/fmed.2022.898592] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 06/14/2022] [Indexed: 12/23/2022] Open
Abstract
The endothelial glycocalyx is a gel-like layer on the luminal side of blood vessels that is composed of glycosaminoglycans and the proteins that tether them to the plasma membrane. Interest in its properties and function has grown, particularly in the last decade, as its importance to endothelial barrier function has come to light. Endothelial glycocalyx studies have revealed that many critical illnesses result in its degradation or removal, contributing to endothelial dysfunction and barrier break-down. Loss of the endothelial glycocalyx facilitates the direct access of immune cells and deleterious agents (e.g., proteases and reactive oxygen species) to the endothelium, that can then further endothelial cell injury and dysfunction leading to complications such as edema, and thrombosis. Here, we briefly describe the endothelial glycocalyx and the primary components thought to be directly responsible for its degradation. We review recent literature relevant to glycocalyx damage in several critical illnesses (sepsis, COVID-19, trauma and diabetes) that share inflammation as a common denominator with actions by several common agents (hyaluronidases, proteases, reactive oxygen species, etc.). Finally, we briefly cover strategies and therapies that show promise in protecting or helping to rebuild the endothelial glycocalyx such as steroids, protease inhibitors, anticoagulants and resuscitation strategies.
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Affiliation(s)
- Eric K. Patterson
- Centre for Critical Illness Research, Lawson Health Research Institute, London, ON, Canada
| | - Gediminas Cepinskas
- Centre for Critical Illness Research, Lawson Health Research Institute, London, ON, Canada
- Department of Medical Biophysics, Western University, London, ON, Canada
| | - Douglas D. Fraser
- Centre for Critical Illness Research, Lawson Health Research Institute, London, ON, Canada
- Department of Pediatrics, Western University, London, ON, Canada
- Department of Physiology and Pharmacology, Western University, London, ON, Canada
- Department of Clinical Neurological Sciences, Western University, London, ON, Canada
- Children’s Health Research Institute, Lawson Health Research Institute, London, ON, Canada
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27
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Dufour-Gaume F, Javelle E, Sailliol A, Cap AP, Prat NJ. COVID-19 : viral infection, endotheliopathy and the immuno-inflammatory response… is it time to consider a standard (non-immunized) plasma therapy approach to maintain homeostasis? Transfus Clin Biol 2022; 29:191-194. [PMID: 35644840 PMCID: PMC9059338 DOI: 10.1016/j.tracli.2022.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 04/26/2022] [Accepted: 04/26/2022] [Indexed: 11/29/2022]
Affiliation(s)
| | - Emilie Javelle
- Hôpital d'Instruction des Armées Laveran, Marseille, France
| | - Anne Sailliol
- Institut de Recherche Biomédicale des Armées, France
| | - Andre P Cap
- U.S. Army Institute of Surgical Research, Houston, USA
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28
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Maiwall R, Bajpai M, Singh A, Agarwal T, Kumar G, Bharadwaj A, Nautiyal N, Tevethia H, Jagdish RK, Vijayaraghavan R, Choudhury A, Mathur RP, Hidam A, Pati NT, Sharma MK, Kumar A, Sarin SK. Standard-Volume Plasma Exchange Improves Outcomes in Patients With Acute Liver Failure: A Randomized Controlled Trial. Clin Gastroenterol Hepatol 2022; 20:e831-e854. [PMID: 33524593 DOI: 10.1016/j.cgh.2021.01.036] [Citation(s) in RCA: 89] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Revised: 12/29/2020] [Accepted: 01/24/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND High volume plasma-exchange (HVPE) improves survival in patients with acute liver failure (ALF), but apprehension regarding volume overload and worsening of cerebral edema remain. METHODS In an open-label randomized controlled trial, 40 consecutive patients of ALF were randomized 1:1 to either standard medical treatment (SMT) or SMT with standard-volume plasma-exchange (SVPE). SVPE was performed using centrifugal apheresis [target volume of 1.5 to 2.0 plasma volumes per session] until desired response was achieved. Cerebral edema was assessed by brain imaging. Results were analyzed in an intention-to-treat analysis. Primary outcome was 21-day transplant-free survival. The levels of cytokines, damage-associated molecular patterns (DAMPs) and endotoxins were analyzed at baseline and day 5. RESULTS ALF patients [aged 31.5 ± 12.2 years, 60% male, 78% viral, 83% hyperacute, 70% with SIRS were included. At day 5, SVPE [mean sessions 2.15 ± 1.42, median plasma volume replaced 5.049 L] compared to SMT alone, resulted in higher lactate clearance (p = .02), amelioration of SIRS (84% vs. 26%; P = .02), reduction in ammonia levels [(221.5 ± 96.9) vs.(439 ± 385.6) μg/dl, P = .02) and SOFA scores [9.9(±3.3) vs. 14.6(±4.8); P = .001]. There were no treatment related deaths. SVPE was associated with a higher 21-day transplant free-survival [75% vs. 45%; P = .04, HR 0.30, 95%CI 0.01-0.88]. A significant decrease in levels of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines along with a decrease in endotoxin and DAMPs was seen with SVPE. CONCLUSION In ALF patients with cerebral edema, SVPE is safe and effective and improves survival possibly by a reduction in cytokine storm and ammonia. CLINICALTRIAL gov (identifier: NCT02718079).
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Meenu Bajpai
- Department of Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Akanksha Singh
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Tanvi Agarwal
- Department of Clinical and Molecular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ankit Bharadwaj
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Nidhi Nautiyal
- Department of Clinical and Molecular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Harsh Tevethia
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rakesh Kumar Jagdish
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rajan Vijayaraghavan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Ashini Hidam
- Department of Clinical and Molecular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Nirupama Trehan Pati
- Department of Clinical and Molecular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Manoj Kumar Sharma
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Anupam Kumar
- Department of Clinical and Molecular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
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29
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Barry M, Pati S. Targeting repair of the vascular endothelium and glycocalyx after traumatic injury with plasma and platelet resuscitation. Matrix Biol Plus 2022; 14:100107. [PMID: 35392184 PMCID: PMC8981767 DOI: 10.1016/j.mbplus.2022.100107] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 02/10/2022] [Accepted: 03/10/2022] [Indexed: 02/06/2023] Open
Abstract
Endothelial glycocalyx shedding is a key instigator of the endotheliopathy of trauma. Plasma and platelet transfusions preserve vascular integrity in pre-clinical models. However, platelets may be less effective than plasma in preserving the glycocalyx. Severely injured patients with hemorrhagic shock can develop endothelial dysfunction, systemic inflammation, and coagulation disturbances collectively known as the endotheliopathy of trauma (EOT). Shedding of the endothelial glycocalyx occurs early after injury, contributes to breakdown of the vascular barrier, and plays a critical role in the pathogenesis of multiple organ dysfunction, leading to poor outcomes in trauma patients. In this review we discuss (i) the pathophysiology of endothelial glycocalyx and vascular barrier breakdown following hemorrhagic shock and trauma, and (ii) the role of plasma and platelet transfusion in maintaining the glycocalyx and vascular endothelial integrity.
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Affiliation(s)
- Mark Barry
- University of California, San Francisco, Department of Surgery. 513 Parnassus Ave., San Francisco, CA 94143, United States
- Corresponding author.
| | - Shibani Pati
- University of California, San Francisco, Department of Surgery. 513 Parnassus Ave., San Francisco, CA 94143, United States
- University of California, San Francisco, Department of Laboratory Medicine. 513 Parnassus Ave., San Francisco, CA 94143, United States
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30
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Farrugia A. Fresh frozen plasma: Beyond coagulation factor content. Transfus Med 2022; 32:178-179. [PMID: 35014091 DOI: 10.1111/tme.12850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Accepted: 01/03/2022] [Indexed: 11/27/2022]
Affiliation(s)
- Albert Farrugia
- School of Surgery, Faculty of Medicine and Medical Sciences, The University of Western Australia, Perth, Australia
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31
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Abstract
ABSTRACT Fluid resuscitation is an essential intervention in critically ill patients, and its ultimate goal is to restore tissue perfusion. Critical illnesses are often accompanied by glycocalyx degradation caused by inflammatory reactions, hypoperfusion, shock, and so forth, leading to disturbed microcirculatory perfusion and organ dysfunction. Therefore, maintaining or even restoring the glycocalyx integrity may be of high priority in the therapeutic strategy. Like drugs, however, different resuscitation fluids may have beneficial or harmful effects on the integrity of the glycocalyx. The purpose of this article is to review the effects of different resuscitation fluids on the glycocalyx. Many animal studies have shown that normal saline might be associated with glycocalyx degradation, but clinical studies have not confirmed this finding. Hydroxyethyl starch (HES), rather than other synthetic colloids, may restore the glycocalyx. However, the use of HES also leads to serious adverse events such as acute kidney injury and bleeding tendencies. Some studies have suggested that albumin may restore the glycocalyx, whereas others have suggested that balanced crystalloids might aggravate glycocalyx degradation. Notably, most studies did not correct the effects of the infusion rate or fluid volume; therefore, the results of using balanced crystalloids remain unclear. Moreover, mainly animal studies have suggested that plasma may protect and restore glycocalyx integrity, and this still requires confirmation by high-quality clinical studies.
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Pape T, Hunkemöller AM, Kümpers P, Haller H, David S, Stahl K. Targeting the "sweet spot" in septic shock - A perspective on the endothelial glycocalyx regulating proteins Heparanase-1 and -2. Matrix Biol Plus 2021; 12:100095. [PMID: 34917926 PMCID: PMC8669377 DOI: 10.1016/j.mbplus.2021.100095] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/20/2021] [Accepted: 11/23/2021] [Indexed: 12/23/2022] Open
Abstract
Sepsis is a life-threatening syndrome caused by a pathological host response to an infection that eventually, if uncontrolled, leads to septic shock and ultimately, death. In sepsis, a massive aggregation of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) cause a cytokine storm. The endothelial glycocalyx (eGC) is a gel like layer on the luminal side of the endothelium that consists of proteoglycans, glycosaminoglycans (GAG) and plasma proteins. It is synthesized by endothelial cells and plays an active role in the regulation of inflammation, permeability, and coagulation. In sepsis, early and profound injury of the eGC is observed and circulating eGC components correlate directly with clinical severity and outcome. The activity of the heparan sulfate (HS) specific glucuronidase Heparanase-1 (Hpa-1) is elevated in sepsis, resulting in shedding of heparan sulfate (HS), a main GAG of the eGC. HS induces endothelial barrier breakdown and accelerates systemic inflammation. Lipopolysaccharide (LPS), a PAMP mainly found on the surface of gram-negative bacteria, activates TLR-4, which results in cytokine production and further activation of Hpa-1. Hpa-1 shed HS fragments act as DAMPs themselves, leading to a vicious cycle of inflammation and end-organ dysfunction such as septic cardiomyopathy and encephalopathy. Recently, Hpa-1's natural antagonist, Heparanase-2 (Hpa-2) has been identified. It has no intrinsic enzymatic activity but instead acts by reducing inflammation. Hpa-2 levels are reduced in septic mice and patients, leading to an acquired imbalance of Hpa-1 and Hpa-2 paving the road towards a therapeutic intervention. Recently, the synthetic antimicrobial peptide 19-2.5 was described as a promising therapy protecting the eGC by inhibition of Hpa-1 activity and HS shed fragments in animal studies. However, a recombinant Hpa-2 therapy does not exist to the present time. Therapeutic plasma exchange (TPE), a modality already tested in clinical practice, effectively removes injurious mediators, e.g., Hpa-1, while replacing depleted protective molecules, e.g., Hpa-2. In critically ill patients with septic shock, TPE restores the physiological Hpa-1/Hpa-2 ratio and attenuates eGC breakdown. TPE results in a significant improvement in hemodynamic instability including reduced vasopressor requirement. Although promising, further studies are needed to determine the therapeutic impact of TPE in septic shock.
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Affiliation(s)
- Thorben Pape
- Division of Nephrology and Hypertension, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
| | - Anna Maria Hunkemöller
- Department of Medicine, Division of General Internal and Emergency Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany
| | - Philipp Kümpers
- Department of Medicine, Division of General Internal and Emergency Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany
| | - Hermann Haller
- Division of Nephrology and Hypertension, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
| | - Sascha David
- Institute of Intensive Care Medicine, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
| | - Klaus Stahl
- Division of Nephrology and Hypertension, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.,Division of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
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33
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Endothelial glycocalyx degradation during sepsis: Causes and consequences. Matrix Biol Plus 2021; 12:100094. [PMID: 34917925 PMCID: PMC8668992 DOI: 10.1016/j.mbplus.2021.100094] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 11/21/2021] [Accepted: 11/23/2021] [Indexed: 12/23/2022] Open
Abstract
The endothelial glycocalyx is a ubiquitous intravascular structure essential for vascular homeostasis. During sepsis, the glycocalyx is degraded via the collective action of a variety of redundant sheddases, the regulation of which remains the focus of active investigation. Septic loss of the glycocalyx imparts both local vascular injury (leading to acute respiratory distress syndrome and acute kidney injury) as well as the systemic consequences of circulating glycosaminoglycan fragments (leading to cognitive dysfunction). Glycocalyx degradation during sepsis is potentially shaped by clinically-modifiable factors, suggesting opportunities for therapeutic intervention to mitigate the end-organ consequences of sepsis. The glycocalyx is a ubiquitous structure found on endothelial cells that extends into the vascular lumen. It is enriched in proteoglycans, which are proteins attached to the glycosaminoglycans heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid. In health and disease, the endothelial glycocalyx is a central regulator of vascular permeability, inflammation, coagulation, and circulatory tonicity. During sepsis, a life-threatening syndrome seen commonly in hospitalized patients, the endothelial glycocalyx is degraded, significantly contributing to its many clinical manifestations. In this review we discuss the intrinsically linked mechanisms responsible for septic endothelial glycocalyx destruction: glycosaminoglycan degradation and proteoglycan cleavage. We then examine the consequences of local endothelial glycocalyx loss to several organ systems and the systemic consequences of shed glycocalyx constituents. Last, we explore clinically relevant non-modifiable and modifiable factors that exacerbate or protect against endothelial glycocalyx shedding during sepsis.
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Key Words
- ADAM, A Disintegrin and Metalloproteinase
- ANP, Atrial Natriuretic Peptide
- ARDS, Acute respiratory distress syndrome
- Ang2, Angiopoietin-2
- DAMP, Damage-associated Molecular Pattern
- Endothelial glycocalyx
- FFP, Fresh Frozen Plasma
- GAG, Glycosaminoglycan
- Glycosaminoglycans
- HPSE-1/2, Heparanase-1/2
- LPS, Lipopolysaccharide
- MMP, Matrix Metalloproteinase
- PG, Proteoglycan
- Proteoglycans
- Sepsis
- TIMP, Tissue inhibitors of matrix metalloproteinase
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Neuenfeldt FS, Weigand MA, Fischer D. Coagulopathies in Intensive Care Medicine: Balancing Act between Thrombosis and Bleeding. J Clin Med 2021; 10:5369. [PMID: 34830667 PMCID: PMC8623639 DOI: 10.3390/jcm10225369] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 11/10/2021] [Accepted: 11/16/2021] [Indexed: 11/23/2022] Open
Abstract
Patient Blood Management advocates an individualized treatment approach, tailored to each patient's needs, in order to reduce unnecessary exposure to allogeneic blood products. The optimization of hemostasis and minimization of blood loss is of high importance when it comes to critical care patients, as coagulopathies are a common phenomenon among them and may significantly impact morbidity and mortality. Treating coagulopathies is complex as thrombotic and hemorrhagic conditions may coexist and the medications at hand to modulate hemostasis can be powerful. The cornerstones of coagulation management are an appropriate patient evaluation, including the individual risk of bleeding weighed against the risk of thrombosis, a proper diagnostic work-up of the coagulopathy's etiology, treatment with targeted therapies, and transfusion of blood product components when clinically indicated in a goal-directed manner. In this article, we will outline various reasons for coagulopathy in critical care patients to highlight the aspects that need special consideration. The treatment options outlined in this article include anticoagulation, anticoagulant reversal, clotting factor concentrates, antifibrinolytic agents, desmopressin, fresh frozen plasma, and platelets. This article outlines concepts with the aim of the minimization of complications associated with coagulopathies in critically ill patients. Hereditary coagulopathies will be omitted in this review.
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Affiliation(s)
| | | | - Dania Fischer
- Department of Anaesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany; (F.S.N.); (M.A.W.)
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35
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Abstract
Liver failure in the context of acute (ALF) and acute on chronic liver failure (ACLF) is associated with high mortality in the absence of a liver transplant. For decades, therapeutic plasma exchange (TPE) is performed for the management of immune-mediated diseases. TPE has emerged as an attractive extracorporeal blood purification technique in patients with ALF and ACLF. The basic premise of using TPE is to remove the toxic substances which would allow recovery of native liver functions by facilitating liver regeneration. In recent years, encouraging data have emerged, suggesting the benefits of TPE in patients with liver failure. TPE has emerged as an attractive liver support device for the failing liver until liver transplantation or clinical recovery. The data in patients with ALF suggest routine use of high-volume TPE, while the data for such a strategy are less robust for patients with ACLF.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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36
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Shinohara A, Ushiyama A, Iijima T. Time-Dependent Dynamics Required for the Degradation and Restoration of the Vascular Endothelial Glycocalyx Layer in Lipopolysaccharide-Treated Septic Mice. Front Cardiovasc Med 2021; 8:730298. [PMID: 34595224 PMCID: PMC8476805 DOI: 10.3389/fcvm.2021.730298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 08/23/2021] [Indexed: 11/16/2022] Open
Abstract
The endothelial glycocalyx (GCX) plays a key role in the development of organ failure following sepsis. Researchers have investigated GCX degradation caused by pathological conditions. Nonetheless, the GCX restoration process remains poorly understood. Herein, we developed a model in which GCX restoration could be reproduced in mice using in vivo imaging and a dorsal skinfold chamber (DSC). The severity of sepsis was controlled by adjusting the dose of lipopolysaccharide (LPS) used to trigger GCX degradation in BALB/c mice. We evaluated the GCX thickness, leukocyte-endothelial interactions, and vascular permeability using in vivo imaging through DSC under intravital microscopy. The plasma concentration of syndecan-1(Sdc-1), a GCX structural component, was also determined as a marker of GCX degradation. Thus, we developed a reproducible spontaneous GCX recovery model in mice. Degraded GCX was restored within 24 h by the direct visualization of the endothelial GCX thickness, and leukocyte-endothelial interactions. In contrast, indirectly related indicators of recovery from sepsis, such as body weight and blood pressure, required a longer recovery time. This model can be used to study intractable angiopathy following sepsis.
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Affiliation(s)
- Akane Shinohara
- Division of Anesthesiology, Department of Perioperative Medicine, Showa University, School of Dentistry, Tokyo, Japan
| | - Akira Ushiyama
- Department of Environmental Health, National Institute of Public Health, Saitama, Japan
| | - Takehiko Iijima
- Division of Anesthesiology, Department of Perioperative Medicine, Showa University, School of Dentistry, Tokyo, Japan
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Tucker H, Davenport R, Green L. The Role of Plasma Transfusion in Pre-Hospital Haemostatic Resuscitation. Transfus Med Rev 2021; 35:91-95. [PMID: 34593289 DOI: 10.1016/j.tmrv.2021.08.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 08/22/2021] [Accepted: 08/23/2021] [Indexed: 12/15/2022]
Abstract
Traumatic haemorrhage remains a major cause of preventable death and early haemostatic resuscitation is now a mainstay of treatment internationally. Recently, 2 randomized control trials (RCTs) - PAMPer (Prehospital Air Medical Plasma) and COMBAT (Control of Major Bleeding After Trauma), evaluating the effect of pre-hospital use of plasma on mortality provided conflicting results, raising important questions on the role of plasma resuscitation in pre-hospital environment. Both PAMPer (n = 501 patients) and COMBAT (n = 144 patients) trials were pragmatic RCTs that evaluated the effect of pre-hospital plasma transfusion (two units) versus standard of care on 28/30 days mortality in trauma patients who presented with clinical signs of haemorrhagic shock (defined as hypotension or tachycardia). The PAMPer trial showed that plasma transfusion reduced 30-day mortality compared with standard of care (23% vs 33%, 95% confidence interval -18.6; -1.0%; P = 0.03), while COMBAT trial showed no difference in 28-day survival. The post-hoc analyses of the 2 trials have suggested that the benefit of pre-hospital plasma transfusion may be greater for patients who are coagulopathic, have blunt injury and have a transport time from the scene of injury to the hospital of >20 minutes. In this review we evaluate strengths and limitations of the two trials and their differences and similarities, which may explain the conflicting results, as well as provide directions for future trials to better define the target population that would most benefit from pre-hospital plasma resuscitation. Further, considering the logistical challenges of carrying any blood components on an aircraft, cost/safety of plasma, and the scarcity of universal blood group donors, there is a need for a health economic evaluation of pre-hospital plasma transfusion in trauma patients, prior to this intervention becoming universal.
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Affiliation(s)
- Harriet Tucker
- Blizard Institute, Queen Mary University of London, London, UK
| | - Ross Davenport
- Blizard Institute, Queen Mary University of London, London, UK; Departmen of Trauma, Barts Health NHS Trust, London, UK
| | - Laura Green
- Blizard Institute, Queen Mary University of London, London, UK; Departmen of Trauma, Barts Health NHS Trust, London, UK; Blood Component division, NHS Blood and Transplant, London, UK.
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38
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Kleinveld DJB, Simons DDG, Dekimpe C, Deconinck SJ, Sloos PH, Maas MAW, Kers J, Muia J, Brohi K, Voorberg J, Vanhoorelbeke K, Hollmann MW, Juffermans NP. Plasma and rhADAMTS13 reduce trauma-induced organ failure by restoring the ADAMTS13-VWF axis. Blood Adv 2021; 5:3478-3491. [PMID: 34505883 PMCID: PMC8525227 DOI: 10.1182/bloodadvances.2021004404] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 05/06/2021] [Indexed: 11/20/2022] Open
Abstract
Trauma-induced organ failure is characterized by endothelial dysfunction. The aim of this study was to investigate the role of von Willebrand factor (VWF) and its cleaving enzyme, ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13) in the occurrence of endothelial permeability and organ failure in trauma. In an observational study in a level-1 trauma center, 169 adult trauma patients with clinical signs of shock and/or severe injuries were included. Trauma was associated with low ADAMTS13 and high VWF antigen levels, thus generating an imbalance of ADAMTS13 to VWF. Patients who developed organ failure (23%) had greater ADAMTS13-to-VWF imbalances, persistently lower platelet counts, and elevated levels of high-molecular-weight VWF multimers compared with those without organ failure, suggesting microthrombi formation. To investigate the effect of replenishing low ADAMTS13 levels on endothelial permeability and organ failure using either recombinant human ADAMTS13 (rhADAMTS13) or plasma transfusion, a rat model of trauma-induced shock and transfusion was used. Rats in traumatic hemorrhagic shock were randomized to receive crystalloids, crystalloids supplemented with rhADAMTS13, or plasma transfusion. A 70-kDa fluorescein isothiocyanate-labeled dextran was injected to determine endothelial leakage. Additionally, organs were histologically assessed. Both plasma transfusion and rhADAMTS13 were associated with a reduction in pulmonary endothelial permeability and organ injury when compared with resuscitation with crystalloids, but only rhADAMTS13 resulted in significant improvement of a trauma-induced decline in ADAMTS13 levels. We conclude that rhADAMTS13 and plasma transfusion can reduce organ failure following trauma. These findings implicate the ADAMTS13-VWF axis in the pathogenesis of organ failure.
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Affiliation(s)
- Derek J B Kleinveld
- Department of Intensive Care Medicine
- Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Derek D G Simons
- Department of Intensive Care Medicine
- Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Charlotte Dekimpe
- Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
| | - Shannen J Deconinck
- Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
| | - Pieter H Sloos
- Department of Intensive Care Medicine
- Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - M Adrie W Maas
- Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jesper Kers
- Department of Pathology, Amsterdam Infection & Immunity Institute, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
| | - Joshua Muia
- Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, Tulsa, OK
| | - Karim Brohi
- Centre for Trauma Sciences, Queen Mary University of London, London, United Kingdom
| | - Jan Voorberg
- Sanquin, Department of Cellular Hemostasis, Amsterdam, The Netherlands
| | - Karen Vanhoorelbeke
- Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
| | - Markus W Hollmann
- Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; and
| | - Nicole P Juffermans
- Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Intensive Care Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
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Bandopadhyay P, Rozario RD, Lahiri A, Sarif J, Ray Y, Paul SR, Roy R, Maiti R, Chaudhuri K, Bagchi S, Maiti A, Perwez MM, Sharma Sarkar B, Roy D, Chakraborty R, Vasudevan JS, Sharma S, Biswas D, Maiti C, Saha B, Bhattacharya P, Pandey R, Chatterjee S, Paul S, Ganguly D. Nature and Dimensions of Systemic Hyperinflammation and its Attenuation by Convalescent Plasma in Severe COVID-19. J Infect Dis 2021; 224:565-574. [PMID: 34398242 PMCID: PMC7928875 DOI: 10.1093/infdis/jiab010] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 01/11/2021] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has led to significant morbidity and mortality. While most suffer from mild symptoms, some patients progress to severe disease with acute respiratory distress syndrome (ARDS) and associated systemic hyperinflammation. METHODS First, to characterize key cytokines and their dynamics in this hyperinflammatory condition, we assessed abundance and correlative expression of a panel of 48 cytokines in patients progressing to ARDS as compared to patients with mild disease. Then, in an ongoing randomized controlled trial of convalescent plasma therapy (CPT), we analyzed rapid effects of CPT on the systemic cytokine dynamics as a correlate for the level of hypoxia experienced by the patients. RESULTS We identified an anti-inflammatory role of CPT independent of its neutralizing antibody content. CONCLUSIONS Neutralizing antibodies, as well as reductions in circulating interleukin-6 and interferon-γ-inducible protein 10, contributed to marked rapid reductions in hypoxia in response to CPT. CLINICAL TRIAL REGISTRY OF INDIA CTRI/2020/05/025209. http://www.ctri.nic.in/.
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Affiliation(s)
- Purbita Bandopadhyay
- IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India
| | - Ranit D’ Rozario
- IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India
| | - Abhishake Lahiri
- Division of Structural Biology & Bioinformatics, CSIR-Indian Institute of Chemical Biology, Kolkata, India
| | - Jafar Sarif
- IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India
| | - Yogiraj Ray
- Department of Medicine, ID & BG Hospital, Kolkata, India
- Department of Tropical Medicine, School of Tropical Medicine, Kolkata, India
| | | | - Rammohan Roy
- Department of Medicine, ID & BG Hospital, Kolkata, India
| | - Rajshekhar Maiti
- Department of Medicine, ID & BG Hospital, Kolkata, India
- Department of Pediatrics, Sagar Dutta Hospital & College of Medicine, Kolkata, India
| | | | - Saugata Bagchi
- Department of Medicine, ID & BG Hospital, Kolkata, India
| | - Ayan Maiti
- Department of Medicine, ID & BG Hospital, Kolkata, India
| | | | | | - Devlina Roy
- Department of Medicine, ID & BG Hospital, Kolkata, India
| | | | | | - Sachin Sharma
- CSIR-Institute of Genomics and Integrative Biology, Delhi, India
| | - Durba Biswas
- Department of Immunohematology & Blood Transfusion, Medical College Hospital, Kolkata, India
| | - Chikam Maiti
- Department of Immunohematology & Blood Transfusion, Medical College Hospital, Kolkata, India
| | - Bibhuti Saha
- Department of Tropical Medicine, School of Tropical Medicine, Kolkata, India
| | - Prasun Bhattacharya
- Department of Immunohematology & Blood Transfusion, Medical College Hospital, Kolkata, India
| | - Rajesh Pandey
- CSIR-Institute of Genomics and Integrative Biology, Delhi, India
| | - Shilpak Chatterjee
- IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India
| | - Sandip Paul
- Division of Structural Biology & Bioinformatics, CSIR-Indian Institute of Chemical Biology, Kolkata, India
| | - Dipyaman Ganguly
- IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India
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40
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Hall K, Drobatz K. Volume Resuscitation in the Acutely Hemorrhaging Patient: Historic Use to Current Applications. Front Vet Sci 2021; 8:638104. [PMID: 34395568 PMCID: PMC8357988 DOI: 10.3389/fvets.2021.638104] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Accepted: 05/21/2021] [Indexed: 11/13/2022] Open
Abstract
Acute hemorrhage in small animals results from traumatic and non-traumatic causes. This review seeks to describe current understanding of the resuscitation of the acutely hemorrhaging small animal (dog and cat) veterinary patient through evaluation of pre-clinical canine models of hemorrhage and resuscitation, clinical research in dogs and cats, and selected extrapolation from human medicine. The physiologic dose and response to whole blood loss in the canine patient is repeatable both in anesthetized and awake animals and is primarily characterized clinically by increased heart rate, decreased systolic blood pressure, and increased shock index and biochemically by increased lactate and lower base excess. Previously, initial resuscitation in these patients included immediate volume support with crystalloid and/or colloid, regardless of total volume, with a target to replace lost vascular volume and bring blood pressure back to normal. Newer research now supports prioritizing hemorrhage control in conjunction with judicious crystalloid administration followed by early consideration for administration of platelets, plasma and red blood during the resuscitation phase. This approach minimizes blood loss, ameliorates coagulopathy, restores oxygen delivery and correct changes in the glycocalyx. There are many hurdles in the application of this approach in clinical veterinary medicine including the speed with which the bleeding source is controlled and the rapid availability of blood component therapy. Recommendations regarding the clinical approach to volume resuscitation in the acutely hemorrhaging veterinary patient are made based on the canine pre-clinical, veterinary clinical and human literature reviewed.
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Affiliation(s)
- Kelly Hall
- Department of Clinical Sciences, Critical Care Services, Colorado State University, Fort Collins, CO, United States
| | - Kenneth Drobatz
- Section of Critical Care, Department of Clinical Studies, University of Pennsylvania, Philadelphia, PA, United States
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41
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Pati S, Fennern E, Holcomb JB, Barry M, Trivedi A, Cap AP, Martin MJ, Wade C, Kozar R, Cardenas JC, Rappold JF, Spiegel R, Schreiber MA. Treating the endotheliopathy of SARS-CoV-2 infection with plasma: Lessons learned from optimized trauma resuscitation with blood products. Transfusion 2021; 61 Suppl 1:S336-S347. [PMID: 34269437 PMCID: PMC8446992 DOI: 10.1111/trf.16452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 03/30/2021] [Indexed: 11/29/2022]
Affiliation(s)
- Shibani Pati
- Department of Lab MedicineUniversity of California San Francisco School of MedicineSan FranciscoCaliforniaUSA
| | - Erin Fennern
- Department of SurgeryMount Sinai Icahn School of MedicineNew YorkNew YorkUSA
| | | | - Mark Barry
- Department of SurgeryUniversity of California San Francisco School of MedicineSan FranciscoCaliforniaUSA
| | - Alpa Trivedi
- Department of Lab MedicineUniversity of California San Francisco School of MedicineSan FranciscoCaliforniaUSA
| | - Andrew P. Cap
- U.S. Army Institute of Surgical ResearchJBSA‐FT Sam HoustonSan AntonioTexasUSA
| | | | - Charles Wade
- Department of Surgery McGovern School of MedicineUniversity of Texas Health Science CenterHoustonTexasUSA
| | - Rosemary Kozar
- Department of SurgeryUniversity of MarylandBaltimoreMarylandUSA
| | - Jessica C. Cardenas
- Department of Surgery McGovern School of MedicineUniversity of Texas Health Science CenterHoustonTexasUSA
| | - Joseph F. Rappold
- Department of Surgery Maine Medical CenterTufts University School of MedicinePortlandMaineUSA
| | - Renee Spiegel
- Department of SurgeryElmhurst Hospital CenterElmhurstNew YorkUSA
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42
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van den Brink DP, Kleinveld DJB, Sloos PH, Thomas KA, Stensballe J, Johansson PI, Pati S, Sperry J, Spinella PC, Juffermans NP. Plasma as a resuscitation fluid for volume-depleted shock: Potential benefits and risks. Transfusion 2021; 61 Suppl 1:S301-S312. [PMID: 34057210 PMCID: PMC8361764 DOI: 10.1111/trf.16462] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 03/04/2021] [Accepted: 03/04/2021] [Indexed: 12/13/2022]
Affiliation(s)
- Daan P. van den Brink
- Department of Intensive Care MedicineAmsterdam UMCAmsterdamThe Netherlands
- Laboratory of Experimental Intensive Care and AnesthesiologyAmsterdam UMCAmsterdamThe Netherlands
| | - Derek J. B. Kleinveld
- Department of Intensive Care MedicineAmsterdam UMCAmsterdamThe Netherlands
- Laboratory of Experimental Intensive Care and AnesthesiologyAmsterdam UMCAmsterdamThe Netherlands
- Department of Trauma SurgeryAmsterdam UMCAmsterdamThe Netherlands
| | - Pieter H. Sloos
- Laboratory of Experimental Intensive Care and AnesthesiologyAmsterdam UMCAmsterdamThe Netherlands
- Department of Trauma SurgeryAmsterdam UMCAmsterdamThe Netherlands
| | | | - Jakob Stensballe
- Department of Anesthesia and Trauma Center, Centre of Head and OrthopedicsRigshospitalet, Copenhagen University HospitalCopenhagenDenmark
- Department of Clinical immunologyRigshospitalet, Copenhagen University HospitalCopenhagenDenmark
| | - Pär I. Johansson
- Department of Clinical immunologyRigshospitalet, Copenhagen University HospitalCopenhagenDenmark
| | - Shibani Pati
- Department of Laboratory MedicineUniversity of California San FranciscoSan FranciscoCaliforniaUSA
| | - Jason Sperry
- Department of Surgery and Critical Care MedicineUniversity of Pittsburgh Medical CenterPittsburghPennsylvaniaUSA
| | | | - Nicole P. Juffermans
- Laboratory of Experimental Intensive Care and AnesthesiologyAmsterdam UMCAmsterdamThe Netherlands
- Department of Intensive CareOLVG HospitalAmsterdamThe Netherlands
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Matsumoto H, Takeba J, Umakoshi K, Kikuchi S, Ohshita M, Annen S, Moriyama N, Nakabayashi Y, Sato N, Aibiki M. ADAMTS13 activity decreases in the early phase of trauma associated with coagulopathy and systemic inflammation: a prospective observational study. Thromb J 2021; 19:17. [PMID: 33712048 PMCID: PMC7953673 DOI: 10.1186/s12959-021-00270-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Accepted: 03/03/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND We conducted a prospective observational study for investigating the changes in the 13th member of a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS13) and its association with the coagulofibrinolytic response in adult trauma patients. METHODS In 39 trauma patients hospitalized for longer than 7 days, time-course changes in biomarkers of coagulofibrinolysis and systemic inflammation along with ADAMTS13 activity were examined. The patients were stratified into three groups based on ADAMTS13 activities on admission (day 0): normal group (≥70%), mildly decreased group (≥50 and < 70%) and moderately decreased group (< 50%). RESULTS Among 39 patients with a median Injury Severity Score (ISS) of 20, 11 patients developed disseminated intravascular coagulation (DIC) and 16 patients required transfusion. Six of 39 patients (15.4%) showed moderate decreased ADAMTS13 activity to < 50%, and 20 patients (51.3%) showed mild drops (≥50 and < 70%). These changes in ADAMTS13 activity on day 0 were significantly correlated with changes in IL-6 and other coagulofibrinolytic markers such as platelet counts, prothrombin time and fibrin/fibrinogen degradation product (FDP). Antithrombin activity (AT) and serum albumin (Alb) level showed significantly positive linear correlations with ADAMTS13 activity (AT: r = 0.513, p < 0.001; Alb: r = 0.647, p < 0.001). Simple logistic regression analyses showed that ADAMTS13 activity, if less than 50%, was significantly correlated with the development of DIC (OR 7.499, 95%CI 1.121-49.242, p = 0.038) and the need for transfusion of fresh frozen plasma (OR 9.000, 95%CI 1.327-61.025, p = 0.028). CONCLUSIONS ADAMTS13 activity decreased even in the early phase of trauma, which was complicated by coagulopathy and systemic inflammation. Furthermore, the decrease in ADAMTS13 activity was correlated with DIC and plasma transfusion.
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Affiliation(s)
- Hironori Matsumoto
- Department of Emergency and Critical Care Medicine, Ehime University, Graduate School of Medicine, Shitsukawa 454, Toon City, Ehime, 791-0295, Japan.
| | - Jun Takeba
- Department of Emergency and Critical Care Medicine, Ehime University, Graduate School of Medicine, Shitsukawa 454, Toon City, Ehime, 791-0295, Japan
| | - Kensuke Umakoshi
- Department of Emergency and Critical Care Medicine, Ehime University, Graduate School of Medicine, Shitsukawa 454, Toon City, Ehime, 791-0295, Japan
| | - Satoshi Kikuchi
- Department of Emergency and Critical Care Medicine, Ehime University, Graduate School of Medicine, Shitsukawa 454, Toon City, Ehime, 791-0295, Japan
| | - Muneaki Ohshita
- Department of Emergency and Critical Care Medicine, Ehime University, Graduate School of Medicine, Shitsukawa 454, Toon City, Ehime, 791-0295, Japan
| | - Suguru Annen
- Department of Emergency and Critical Care Medicine, Ehime University, Graduate School of Medicine, Shitsukawa 454, Toon City, Ehime, 791-0295, Japan
| | - Naoki Moriyama
- Department of Emergency and Critical Care Medicine, Ehime University, Graduate School of Medicine, Shitsukawa 454, Toon City, Ehime, 791-0295, Japan
| | - Yuki Nakabayashi
- Department of Emergency and Critical Care Medicine, Ehime University, Graduate School of Medicine, Shitsukawa 454, Toon City, Ehime, 791-0295, Japan
| | - Norio Sato
- Department of Emergency and Critical Care Medicine, Ehime University, Graduate School of Medicine, Shitsukawa 454, Toon City, Ehime, 791-0295, Japan
| | - Mayuki Aibiki
- Department of Emergency and Critical Care Medicine, Ehime University, Graduate School of Medicine, Shitsukawa 454, Toon City, Ehime, 791-0295, Japan
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Veraar C, Schwarz S, Thanner J, Direder M, Boehm PM, Harnoncourt L, Ortmayr J, Veraar C, Mascherbauer J, Klepetko W, Dworschak M, Ankersmit HJ, Moser B. Transient perioperative inflammation following lung transplantation and major thoracic surgery with elective extracorporeal support: a prospective observational study. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:385. [PMID: 33842606 PMCID: PMC8033292 DOI: 10.21037/atm-20-4771] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Background The clinical relevance of inflammation induced by elective perioperative extracorporeal membrane oxygenation (ECMO) usage as an integral part of modern lung transplantation (LUTX) remains elusive. The aim of this study was to determine the perioperative cytokine response accompanying major thoracic surgery employing different extracorporeal devices comprising ECMO, cardiopulmonary bypass (CPB), or no extracorporeal circulation in relation to inflammation, clinically tangible as increased sequential organ failure assessment (SOFA) score, called SOFA. Methods In this prospective, observational pilot study 42 consecutive patients with end-stage pulmonary disease undergoing LUTX; 15 patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy and 15 patients with lung cancer undergoing major lung resections were analysed. Cytokine serum concentrations and SOFA were determined before, at end of surgery and in the following postoperative days. Results LUTX on ECMO and pulmonary endarterectomy (PEA) on CPB triggered an immediate increase in cytokine serum concentrations at end of surgery: IL-6: 66-fold and 71-fold, IL-10: 3-fold and 2.5-fold, ST2/IL-33R: 5-fold and 4-fold and SOFA: 10.5±2.8 and 10.7±1.7, that decreased sharply to baseline levels from postoperative day 1–5. Despite low perioperative mortality (3 patients, 4.1%) extremely high SOFA ≥13 was associated with mortality after LUTX. Delta-SOFA distinguished survivors from non-survivors: −4.5±3.2 vs. −0.3±1.5 (P=0.001). Increased IL-6 serum concentrations were predictive for increased SOFA (sensitivity: 97%, specificity: 80%). Peak cytokine serum concentrations correlated with ECC duration, maximal lactate, transfusion of red-blood-cells, fresh-frozen-plasma, and catecholamine support. Conclusions LUTX and PEA on extracorporeal circulation with an excellent outcome triggered an immediate rise and concomitant fall of inflammation as observed in cytokine serum concentrations and SOFA. High absolute SOFA in the presence of an uncomplicated postoperative course may pertain to specific management strategies rather than organ failure.
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Affiliation(s)
- Cecilia Veraar
- Department of Anaesthesiology, General Intensive Care and Pain Medicine, Division of Cardiothoracic and Vascular Anaesthesia and Intensive Care Medicine, Medical University of Vienna, Vienna, Austria
| | - Stefan Schwarz
- Department of Surgery, Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Jürgen Thanner
- Department of Surgery, Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Martin Direder
- Department of Surgery, Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Panja M Boehm
- Department of Surgery, Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Leopold Harnoncourt
- Department of Surgery, Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Joachim Ortmayr
- Department of Surgery, Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Clarence Veraar
- Department of Surgery, Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Julia Mascherbauer
- Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
| | - Walter Klepetko
- Department of Surgery, Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Martin Dworschak
- Department of Anaesthesiology, General Intensive Care and Pain Medicine, Division of Cardiothoracic and Vascular Anaesthesia and Intensive Care Medicine, Medical University of Vienna, Vienna, Austria
| | - Hendrik J Ankersmit
- Department of Surgery, Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.,Head FFG Project "APOSEC", FOLAB Surgery, Medical University Vienna, Vienna, Austria
| | - Bernhard Moser
- Department of Surgery, Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
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Montealegre F, Lyons BM. Fluid Therapy in Dogs and Cats With Sepsis. Front Vet Sci 2021; 8:622127. [PMID: 33718468 PMCID: PMC7947228 DOI: 10.3389/fvets.2021.622127] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 02/03/2021] [Indexed: 01/20/2023] Open
Abstract
Sepsis is currently defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis may occur secondary to infection anywhere in the body, and its pathogenesis is complex and not yet fully understood. Variations in the host immune response result in diverse clinical manifestations, which complicates clinical recognition and fluid therapy both in humans and veterinary species. Septic shock is a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Although septic shock is a form of distributive shock, septic patients frequently present with hypovolemic and cardiogenic shock as well, further complicating fluid therapy decisions. The goals of this review are to discuss the clinical recognition of sepsis in dogs and cats, the basic mechanisms of its pathogenesis as it affects hemodynamic function, and considerations for fluid therapy. Important pathophysiologic changes, such as cellular interaction, microvascular alterations, damage to the endothelial glycocalyx, hypoalbuminemia, and immune paralysis will be also reviewed. The advantages and disadvantages of treatment with crystalloids, natural and synthetic colloids, and blood products will be discussed. Current recommendations for evaluating fluid responsiveness and the timing of vasopressor therapy will also be considered. Where available, the veterinary literature will be used to guide recommendations.
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Affiliation(s)
- Federico Montealegre
- Department of Medical and Scientific Affairs, Nova Biomedical, Waltham, MA, United States
| | - Bridget M Lyons
- Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, United States
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Beattie G, Cohan CM, Ng VL, Victorino GP. Liquid plasma: A solution to optimizing early and balanced plasma resuscitation in massive transfusion. J Trauma Acute Care Surg 2021; 89:488-495. [PMID: 32520899 DOI: 10.1097/ta.0000000000002822] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Early and balanced resuscitation for traumatic hemorrhagic shock is associated with decreased mortality, making timely plasma administration imperative. However, fresh frozen plasma (FFP) thaw time can delay administration, and the shelf life of thawed FFP limits supply and may incur wastage. Liquid plasma (LP) offers an attractive alternative given immediate transfusion potential and extended shelf life. As such, we hypothesized that the use of LP in the massive transfusion protocol (MTP) would improve optimal plasma/red blood cell (RBC) ratios, initial plasma transfusion times, and clinical outcomes in the severely injured patient. METHODS Using Trauma Quality Improvement Program data from our level 1 trauma center, we evaluated MTP activations from 2016 to 2018. Type A LP use was instated April 2017. Before this, thawed FFP was solely used. Plasma/RBC ratios and initial plasma transfusion times were compared in MTP patients before and after LP implementation. Patient and injury characteristics were accounted for using linear regression analysis. Secondary outcomes of mortality, 28-day recovery, and complications were evaluated using Cox proportional hazards regression. RESULTS A total of 95 patients were included (pre-LP, 39; post-LP, 56). Time to initial plasma transfusion and plasma/RBC ratios at 4 and 24 hours were improved post-LP implementation with a coinciding reduction in RBC units transfused (p < 0.05). In a 28-day Cox proportional hazards regression LP implementation was associated with favorable recovery (hazard ratio, 3.16; 95% confidence interval, 1.60-6.24; p < 0.001) and reduction in acute kidney injury (hazard ratio, 0.092; 95% confidence interval, 0.011-0.77; p = 0.027). No post-LP patients with blood group type B or AB (n = 9) demonstrated evidence of hemolysis within 24 hours of type A LP transfusion. CONCLUSION Initial resuscitation with LP optimizes early plasma administration and improves adherence to transfusion ratio guidelines. Furthermore, LP offers a solution to inherent delays with FFP and is associated with improved clinical outcomes, particularly 28-day recovery and odds of acute kidney injury. Liquid plasma should be considered as an alternative to FFP in MTPs. LEVEL OF EVIDENCE Therapeutic/care management, level IV.
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Affiliation(s)
- Genna Beattie
- From the Department of Surgery (G.B., C.M.C., G.P.V.), University of California San Francisco, East Bay; and Department of Laboratory Medicine and Pathology (V.L.N.), Highland Hospital, Oakland, California
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Dolmatova EV, Wang K, Mandavilli R, Griendling KK. The effects of sepsis on endothelium and clinical implications. Cardiovasc Res 2021; 117:60-73. [PMID: 32215570 PMCID: PMC7810126 DOI: 10.1093/cvr/cvaa070] [Citation(s) in RCA: 135] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 02/03/2020] [Accepted: 03/20/2020] [Indexed: 12/15/2022] Open
Abstract
ABSTRACT Sepsis accounts for nearly 700 000 deaths in Europe annually and is caused by an overwhelming host response to infection resulting in organ failure. The endothelium is an active contributor to sepsis and as such represents a major target for therapy. During sepsis, endothelial cells amplify the immune response and activate the coagulation system. They are both a target and source of inflammation and serve as a link between local and systemic immune responses. In response to cytokines produced by immune cells, the endothelium expresses adhesion molecules and produces vasoactive compounds, inflammatory cytokines, and chemoattractants, thus switching from an anticoagulant to procoagulant state. These responses contribute to local control of infection, but systemic activation can lead to microvascular thrombosis, capillary permeability, hypotension, tissue hypoxia, and ultimately tissue damage. This review focuses on the role of the endothelium in leucocyte adhesion and transmigration as well as production of reactive oxygen and nitrogen species, microRNAs and cytokines, formation of signalling microparticles, and disseminated intravascular coagulation. We also discuss alterations in endothelial permeability and apoptosis. Finally, we review the diagnostic potential of endothelial markers and endothelial pathways as therapeutic targets for this devastating disease.
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Affiliation(s)
- Elena V Dolmatova
- Division of Cardiology, Department of Medicine, Emory University, 101 Woodruff Circle, Atlanta, GA 30322, USA
| | - Keke Wang
- Division of Cardiology, Department of Medicine, Emory University, 101 Woodruff Circle, Atlanta, GA 30322, USA
| | - Rohan Mandavilli
- Division of Cardiology, Department of Medicine, Emory University, 101 Woodruff Circle, Atlanta, GA 30322, USA
| | - Kathy K Griendling
- Division of Cardiology, Department of Medicine, Emory University, 101 Woodruff Circle, Atlanta, GA 30322, USA
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Klompas AM, Klassen SA, Senefeld JW, Joyner MJ, Johnson PW, Carter RE, Van Buskirk CM, Winters JL, Stubbs JR. In Reply - Micro-Thrombosis, Perfusion Defects, and Worsening Oxygenation in COVID-19 Patients: A Word of Caution on the Use of Convalescent Plasma. Mayo Clin Proc 2021; 96:259-261. [PMID: 33413824 PMCID: PMC7608008 DOI: 10.1016/j.mayocp.2020.10.036] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 10/29/2020] [Indexed: 01/15/2023]
Affiliation(s)
- Allan M Klompas
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Stephen A Klassen
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Jonathon W Senefeld
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Michael J Joyner
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Patrick W Johnson
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL
| | - Rickey E Carter
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL
| | | | - Jeffrey L Winters
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - James R Stubbs
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
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Juffermans NP, van den Brom CE, Kleinveld DJB. Targeting Endothelial Dysfunction in Acute Critical Illness to Reduce Organ Failure. Anesth Analg 2020; 131:1708-1720. [PMID: 33186159 DOI: 10.1213/ane.0000000000005023] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
During hyperinflammatory conditions that can occur in acute critical illness, such as shock or hypoperfusion, inflammatory mediators activate the endothelium, fueling a proinflammatory host-response as well as procoagulant processes. These changes result in shedding of the glycocalyx, endothelial hyperpermeability, edema formation, and lead to disturbed microcirculatory perfusion and organ failure. Different fluid strategies that are used in shock may have differential effects on endothelial integrity. Collectively, low protein content fluids seem to have negative effects on the endothelial glycocalyx, aggravating endothelial hyperpermeability, whereas fluids containing albumin or plasma proteins may be superior to normal saline in protecting the glycocalyx and endothelial barrier function. Targeting the endothelium may be a therapeutic strategy to limit organ failure, which hitherto has not received much attention. Treatment targets aimed at restoring the endothelium should focus on maintaining glycocalyx function and/or targeting coagulation pathways or specific endothelial receptors. Potential treatments could be supplementing glycocalyx constituents or inhibiting glycocalyx breakdown. In this review, we summarize mechanisms of endothelial dysfunction during acute critical illness, such as the systemic inflammatory response, shedding of the glycocalyx, endothelial activation, and activation of coagulation. In addition, this review focuses on the effects of different fluid strategies on endothelial permeability. Also, potential mechanisms for treatment options to reduce endothelial hyperpermeability with ensuing organ failure are evaluated. Future research is needed to elucidate these pathways and to translate these data to the first human safety and feasibility trials.
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Affiliation(s)
- Nicole P Juffermans
- From the Department of Intensive Care, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands.,Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Charissa E van den Brom
- Department of Anesthesiology, Amsterdam UMC, VU Amsterdam, Amsterdam, the Netherlands.,Experimental Laboratory for Vital Signs, Amsterdam UMC, VU Amsterdam, Amsterdam, the Netherlands
| | - Derek J B Kleinveld
- Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.,Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
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Wirtz MR, van den Brink DP, Roelofs JJTH, Goslings JC, Juffermans NP. Therapeutic application of recombinant human ADAMTS-13 improves shock reversal and coagulation status in a trauma hemorrhage and transfusion rat model. Intensive Care Med Exp 2020; 8:42. [PMID: 33336308 PMCID: PMC7746419 DOI: 10.1186/s40635-020-00328-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 07/16/2020] [Indexed: 12/29/2022] Open
Abstract
INTRODUCTION In hemorrhaging trauma patients, the endothelium is activated, resulting in excessive endothelial synthesis of von Willebrand Factor (vWF), which may enhance micro-thrombi formation, resulting in obstruction of the microcirculation and endothelial injury, aggravating bleeding, as well as contributing to organ failure. Under normal conditions, vWF is cleaved by the metalloprotease ADAMTS-13. After trauma, ADAMTS-13 levels are reduced. OBJECTIVES To assess whether recombinant human ADAMTS-13 inhibits endothelial injury and organ failure in a rat trauma-transfusion model. METHODS Blood products were prepared from syngeneic rat blood according to blood bank standards. Polytrauma was induced in rats by crush injury to the intestines and liver and by fracture of the femur. The rats were hemorrhaged until a mean arterial pressure (MAP) of 40 mmHg was reached. Rats were randomized to receive transfusion of RBCs, FFPs, and platelets in a 1:1:1 ratio to achieve a MAP of 70 mmHg, with or without the addition of ADAMTS-13 (50 μg/kg). Blood samples were assessed for biochemistry and rotational thromboelastometry (ROTEM). Syndecan-1 and VE-cadherin levels were measured as a reflection of endothelial integrity. The amount of leakage of dextran-FITC from the vascular system to the parenchyma in lungs was quantified. To assess inflammation, IL-6 and IL-8 levels were determined. Organ damage was assessed by histopathology. RESULTS All rats were severely shocked, with no significant differences in shock parameters between groups. Rats treated with ADAMTS-13 showed signs of a more effective shock reversal (higher blood pressure, lower lactate levels) compared to controls. Also, ROTEM parameters of clot formation in rats receiving ADAMTS-13 improved compared to controls, which was mainly platelet-dependent. Syndecan-1 levels relative to baseline trended to be lower in ADAMTS-13 treated rats compared to controls (107 vs 149%, p = 0.08). ADAMTS-13 reduced albuminuria (1.7 vs 4.4 g/L, p < 0.01) and organ-specific inflammation (pulmonary IL-6 243 vs 369 pg/mL, p = 0.08; splenic IL-6 253 vs 307, p = 0.03) compared to controls, but did not improve histopathological scores. CONCLUSIONS The use of ADAMTS-13 in a rat trauma-transfusion model improves parameters of shock, platelet-driven coagulation, endothelial damage, and organ inflammation. These results suggest that ADAMTS-13 is important in mediating outcome of trauma. Whether ADAMTS-13 can be used as a therapeutic adjunct to treat bleeding trauma patients remains to be determined.
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Affiliation(s)
- Mathijs R Wirtz
- Department of Intensive Care Medicine, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands. .,Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands. .,Department of Trauma Surgery, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands.
| | - Daan P van den Brink
- Department of Intensive Care Medicine, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands.,Department of Trauma Surgery, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands
| | - Joris J T H Roelofs
- Department of Pathology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands
| | - J Carel Goslings
- Department of Trauma Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - Nicole P Juffermans
- Department of Intensive Care Medicine, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands.,Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands
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