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1.
J Spec Oper Med ; 21(3): 66-70, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34529808

RESUMO

BACKGROUND: United States Africa Command (US AFRICOM) is one of six US Defense Department's geographic combatant commands and is responsible to the Secretary of Defense for military relations with African nations, the African Union, and African regional security organizations. A full-spectrum combatant command, US AFRICOM is responsible for all US Department of Defense operations, exercises, and security cooperation on the African continent, its island nations, and surrounding waters. We seek to characterize blood product administration within AFRICOM using the in-transit visibility tracking tool known as TRAC2ES (TRANSCOM Regulating and Command & Control Evacuation System). METHODS: We performed a retrospective review of TRAC2ES medical evacuations from the AFRICOM theater of operations conducted between 1 January 2008 and 31 December 2018. RESULTS: During this time, there were 963 cases recorded in TRAC2ES originating within AFRICOM, of which 10 (1%) cases received blood products. All patients were males. One was a Department of State employee, one was a military working dog, and the remainder were military personnel. Of the ten humans, seven were the result of trauma, most by way of gunshot wound, and three were due to medical causes. Among human subjects receiving blood products for traumatic injuries, a total of 5 units of type O negative whole blood, 29 units of packed red blood cells (pRBCs), and 9 units of fresh frozen plasma (FFP) were transfused. No subjects underwent massive transfusion of blood products, and only one subject received pRBCs and FFP in 1:1 fashion. All subjects survived until evacuation. CONCLUSIONS: Within the TRAC2ES database, blood product administration within AFRICOM was infrequent, with some cases highlighting lack of access to adequate blood products. Furthermore, the limitations within this database highlight the need for systems designed to capture medical care performance improvement, as this database is not designed to support such analyses. A mandate for performance improvement within AFRICOM that is similar to that of the US Central Command would be beneficial if major improvements are to occur.


Assuntos
Militares , Ferimentos e Lesões , Ferimentos por Arma de Fogo , Animais , Transfusão de Sangue , Cães , Humanos , Masculino , Plasma , Estudos Retrospectivos , Estados Unidos , Ferimentos por Arma de Fogo/terapia
2.
Artigo em Inglês | MEDLINE | ID: mdl-34407003

RESUMO

OBJECTIVE: Gut dysbiosis, an imbalance in the gut microbiome, occurs after trauma which may be ameliorated with transfusion. We hypothesized that gut hypoperfusion following trauma causes dysbiosis and that whole blood (WB) resuscitation mitigates these effects. METHODS: Anesthetized rats underwent sham (S; laparotomy only, n = 6), polytrauma (T; laparotomy, liver and skeletal muscle crush injuries and femur fracture, n = 5), polytrauma and 40% hemorrhage (H; n = 7) and polytrauma, hemorrhage and WB resuscitation (R; n = 7) which was given as 20% estimated blood volume from donor rats 1 hr post-trauma. Baseline cecal mesenteric tissue oxygen (O2) concentration was measured following laparotomy and at 1- and 2 hrs post-trauma. Fecal samples were collected pre-injury and at euthanasia (2 hrs). 16 s rRNA sequencing was performed on purified DNA, and diversity and phylogeny analyzed with QIIME using the Greengenes 16S rRNA database (OTUs; 97% similarity). Alpha- and ß-diversity were estimated using observed species metrics. Permutational analysis of variance was performed for overall significance. RESULTS: In H rats, an average decline of 36% ±3.6 was seen in the mesenteric O2 concentration at 1 hr without improvement by 2 hrs post-injury, which was reversed following resuscitation at 2 hrs post-injury (4.1% ±3.1 difference from baseline). There was no change in tissue O2 concentration in the S or T rats. ß-diversity differed amongst groups for all measured indices except Bray-Curtis, with the spatial median of the S and R rats more similar compared to S and H rats (p < 0.05). While there was no difference in α-diversity found amongst the groups, indices were significantly correlated with mesenteric O2 concentration. Members of the family Enterobacteriaceae were significantly enriched in only 2 hrs. CONCLUSIONS: Mesenteric perfusion after trauma and hemorrhage is restored with WB resuscitation, which influences ß-diversity of the gut microbiome. WB resuscitation may also mitigate the effects of hemorrhage on intestinal dysbiosis, thereby influencing outcomes. LEVEL OF EVIDENCE: N/A - Basic ScienceStudy TypeOriginal Article.

3.
Hematology ; 26(1): 601-611, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34411495

RESUMO

There has been renewed interest in the use of low titer group O whole blood (LTOWB) for the resuscitation of civilian casualties. LTOWB offers several advantages over conventional components such as providing balanced resuscitation in one bag that contains less additive/preservative solution than an equivalent volume of conventional components, is easier and faster to transfuse than multiple components, avoids blood product ratio confusion, contains cold stored platelets, and reduces donor exposures. The resurgence in its use in the resuscitation of civilian trauma patients has led to the publication of an increasing number of studies on its use, primarily amongst adult recipients but also in pediatric patients. These studies have indicated that hemolysis does not occur amongst adult and pediatric non-group O recipients of a modest quantity of LTOWB. The published studies to date on mortality have shown conflicting results with some demonstrating a reduction following LTOWB transfusion while most others have not shown a reduction; there have not been any studies to date that have found significantly increased overall mortality amongst LTOWB recipients. Similarly, when other clinical outcomes, such as venous thromboembolism, sepsis, hospital or intensive care unit lengths of stay are evaluated, LTOWB recipients have not demonstrated worse outcomes compared to conventional component recipients. While definitive proof of the trends in these morbidity and mortality outcomes awaits confirmation in randomized controlled trials, the evidence to date indicates the safety of transfusing LTOWB to injured civilians.


Assuntos
Transfusão de Sangue/métodos , Ressuscitação/métodos , Ferimentos e Lesões/terapia , Sistema ABO de Grupos Sanguíneos/sangue , Doadores de Sangue , Preservação de Sangue , Humanos , Reação Transfusional , Resultado do Tratamento , Ferimentos e Lesões/sangue
4.
J Trauma Acute Care Surg ; 91(2S Suppl 2): S26-S32, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34324470

RESUMO

ABSTRACT: Synthetic biology adopts an engineering design approach to create innovative treatments that are reliable, scalable, and customizable to individual patients. Interest in substitutes for allogenic blood components, primarily red blood cells and platelets, increased in the 1980s because of concerns over infectious disease transmission. However, only now, with emerging synthetic approaches, are such substitutes showing genuine promise. Affordable alternatives to donated blood would be of enormous benefit worldwide. Several approaches to replacing the oxygen-carrying function of red cells are under advanced investigation. Hemoglobin-based oxygen carriers incorporate modifications to reduce the renal toxicity and nitric oxide scavenging of free hemoglobin. While use of earlier-generation hemoglobin-based oxygen carriers may be limited to circumstances in which blood transfusion is not an option, recent advances in chemical modification of hemoglobin may eventually overcome such problems. Another approach encases hemoglobin molecules in biocompatible synthetic nanoparticles. An alternative is the ex vivo production of red cells in bioreactors, with or without genetic manipulation, that offers the potential of a universal donor product. Various strategies to manufacture synthetic platelets are also underway, ranging from simple phospholipid liposomes encapsulating adenosine diphosphate and decorated with fibrinogen fragments, to more complex capsules with multiple receptor peptide sequences. Ex vivo production of platelets in bioreactors is also possible including, for example, platelets derived from induced pluripotent stem cells that are differentiated into a megakaryocytic lineage. Prior to clinical use, trials assessing synthetic blood components must evaluate meaningful safety and effectiveness outcomes in relatively large numbers of critically ill patients. Overcoming these challenges may be as much a hurdle as product design. This article reviews the state of the science of the synthetic biology approach to developing blood component substitutes.


Assuntos
Substitutos Sanguíneos/uso terapêutico , Lesões Relacionadas à Guerra/terapia , Plaquetas , Transfusão de Sangue/métodos , Eritrócitos , Humanos
6.
Surgery ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34253322

RESUMO

BACKGROUND: Death from uncontrolled hemorrhage occurs rapidly, particularly among combat casualties. The US military has used warm fresh whole blood during combat operations owing to clinical and operational exigencies, but published outcomes data are limited. We compared early mortality between casualties who received warm fresh whole blood versus no warm fresh whole blood. METHODS: Casualties injured in Afghanistan from 2008 to 2014 who received ≥2 red blood cell containing units were reviewed using records from the Joint Trauma System Role 2 Database. The primary outcome was 6-hour mortality. Patients who received red blood cells solely from component therapy were categorized as the non-warm fresh whole blood group. Non- warm fresh whole blood patients were frequency-matched to warm fresh whole blood patients on identical strata by injury type, patient affiliation, tourniquet use, prehospital transfusion, and average hourly unit red blood cell transfusion rates, creating clinically unique strata. Multilevel mixed effects logistic regression adjusted for the matching, immortal time bias, and other covariates. RESULTS: The 1,105 study patients (221 warm fresh whole blood, 884 non-warm fresh whole blood) were classified into 29 unique clinical strata. The adjusted odds ratio of 6-hour mortality was 0.27 (95% confidence interval 0.13-0.58) for the warm fresh whole blood versus non-warm fresh whole blood group. The reduction in mortality increased in magnitude (odds ratio = 0.15, P = .024) among the subgroup of 422 patients with complete data allowing adjustment for seven additional covariates. There was a dose-dependent effect of warm fresh whole blood, with patients receiving higher warm fresh whole blood dose (>33% of red blood cell-containing units) having significantly lower mortality versus the non-warm fresh whole blood group. CONCLUSION: Warm fresh whole blood resuscitation was associated with a significant reduction in 6-hour mortality versus non-warm fresh whole blood in combat casualties, with a dose-dependent effect. These findings support warm fresh whole blood use for hemorrhage control as well as expanded study in military and civilian trauma settings.

7.
Transfusion ; 61 Suppl 1: S68-S79, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269433

RESUMO

Although it is well established that transfusion of platelets in cases of severe bleeding reduces mortality, the availability of platelets is hampered by harsh restrictions on shelf life due to elevated risks of microbial contamination and functional losses with room temperature-stored platelets (RTP) kept at 22°C. In contrast, many recent studies have shown that 4°C cold-stored platelets (CSP) are able to overcome these shortcomings leading to the recent Food and Drug Administration licensure for 14-day stored CSP when conventional platelets are unavailable. This work expands the evidence supporting superiority of CSP function by assaying the less explored platelet-mediated clot retraction of RTP and CSP in either autologous plasma (AP) or platelet additive solution (PAS) for up to 21 days. The results demonstrate that CSP have better preservation of contractile function, exhibiting retraction for up to 21 days in both AP and PAS and forming highly ordered fibrin scaffolds similar to those of fresh platelets. In contrast, RTP stored in AP showed impaired contractile function by Day 5 with no retraction after 10 days, whereas PAS-stored RTP retained contractile function for up to 21 days. Collectively, these findings support extended storage of CSP and suggest that storage in PAS can mitigate functional losses in RTP.


Assuntos
Plaquetas/citologia , Preservação de Sangue/métodos , Coagulação Sanguínea , Plaquetas/metabolismo , Fibrina/metabolismo , Humanos , Testes de Função Plaquetária , Refrigeração , Temperatura
8.
Transfusion ; 61 Suppl 1: S234-S242, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269435

RESUMO

BACKGROUND: Acetaminophen (APAP) is a widely self-prescribed analgesic for mild to moderate pain, but overdose or repeat doses can lead to liver injury and death. Kalyra Pharmaceuticals has developed a novel APAP analog, KP-1199, currently in Phase 1 clinical studies, which lacks hepatotoxicity. In this study, the authors evaluated the antinociceptive effect of KP-1199 on thermal injury-induced nociceptive behaviors as well as hemostatic parameters using human blood samples. METHODS: Full-thickness thermal injury was induced in anesthetized adult male Sprague-Dawley rats. On day 7 post-injury, KP-1199 (30 and 60 mg/kg) or APAP (60 mg/kg) was administered orally. Antinociception of KP-1199 and APAP were assessed at multiple time points using Hargreaves' test. In separate experiments, human whole blood was collected and treated with either KP-1199, APAP, or Vehicle (citrate buffer) at 1× (214 µg/ml) and 10× (2140 µg/ml) concentrations. The treated blood samples were assessed for: clotting function, thrombin generation, and platelet activation. RESULTS: APAP did not produce antinociceptive activity. KP-1199 treatment significantly increased the nociceptive threshold, and the antinociceptive activity persisted up to 3 h post-treatment. In human samples, 10× APAP caused significantly prolonged clotting times and increased platelet activation, whereas KP-1199 had caused no negative effects on either parameter tested. CONCLUSION: These results suggest that KP-1199 possesses antinociceptive activity in a rat model of thermal injury. Since KP-1199 does not induce platelet activation or inhibit coagulation, it presents an attractive alternative to APAP for analgesia, especially for battlefield or surgical scenarios where blood loss and blood clotting are of concern.


Assuntos
Acetaminofen/análogos & derivados , Acetaminofen/farmacologia , Analgésicos/química , Analgésicos/farmacologia , Hemostasia/efeitos dos fármacos , Hiperalgesia/tratamento farmacológico , Acetaminofen/administração & dosagem , Acetaminofen/uso terapêutico , Administração Oral , Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Animais , Humanos , Hiperalgesia/sangue , Masculino , Ratos Sprague-Dawley
9.
Transfusion ; 61 Suppl 1: S333-S335, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269445

RESUMO

Hemorrhage is the most common mechanism of death in battlefield casualties with potentially survivable injuries. There is evidence that early blood product transfusion saves lives among combat casualties. When compared to component therapy, fresh whole blood transfusion improves outcomes in military settings. Cold-stored whole blood also improves outcomes in trauma patients. Whole blood has the advantage of providing red cells, plasma, and platelets together in a single unit, which simplifies and speeds the process of resuscitation, particularly in austere environments. The Joint Trauma System, the Defense Committee on Trauma, and the Armed Services Blood Program endorse the following: (1) whole blood should be used to treat hemorrhagic shock; (2) low-titer group O whole blood is the resuscitation product of choice for the treatment of hemorrhagic shock for all casualties at all roles of care; (3) whole blood should be available within 30 min of casualty wounding, on all medical evacuation platforms, and at all resuscitation and surgical team locations; (4) when whole blood is not available, component therapy should be available within 30 min of casualty wounding; (5) all prehospital medical providers should be trained and logistically supported to screen donors, collect fresh whole blood from designated donors, transfuse blood products, recognize and treat transfusion reactions, and complete the minimum documentation requirements; (6) all deploying military personnel should undergo walking blood bank prescreen laboratory testing for transfusion transmitted disease immediately prior to deployment. Those who are blood group O should undergo anti-A/anti-B antibody titer testing.


Assuntos
Transfusão de Sangue/métodos , Ressuscitação/métodos , Choque Hemorrágico/terapia , Ferimentos e Lesões/terapia , Bancos de Sangue/métodos , Serviços Médicos de Emergência/métodos , Humanos , Medicina Militar , Militares
11.
Transfusion ; 61 Suppl 1: S313-S325, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269450

RESUMO

BACKGROUND: The current global pandemic has created unprecedented challenges in the blood supply network. Given the recent shortages, there must be a civilian plan for massively bleeding patients when there are no blood products on the shelf. Recognizing that the time to death in bleeding patients is less than 2 h, timely resupply from unaffected locations is not possible. One solution is to transfuse emergency untested whole blood (EUWB), similar to the extensive military experience fine-tuned over the last 19 years. While this concept is anathema in current civilian transfusion practice, it seems prudent to have a vetted plan in place. METHODS AND MATERIALS: During the early stages of the 2020 global pandemic, a multidisciplinary and international group of clinicians with broad experience in transfusion medicine communicated routinely. The result is a planning document that provides both background information and a high-level guide on how to emergently deliver EUWB for patients who would otherwise die of hemorrhage. RESULTS AND CONCLUSIONS: Similar plans have been utilized in remote locations, both on the battlefield and in civilian practice. The proposed recommendations are designed to provide high-level guidance for experienced blood bankers, transfusion experts, clinicians, and health authorities. Like with all emergency preparedness, it is always better to have a well-thought-out and trained plan in place, rather than trying to develop a hasty plan in the midst of a disaster. We need to prevent the potential for empty shelves and bleeding patients dying for lack of blood.


Assuntos
Bancos de Sangue , Bancos de Sangue/métodos , Preservação de Sangue/métodos , Transfusão de Sangue/métodos , COVID-19/epidemiologia , Defesa Civil , Serviço Hospitalar de Emergência , Humanos , Pandemias
12.
Transfusion ; 61 Suppl 1: S183-S187, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269462

RESUMO

BACKGROUND: Donated blood is a valuable and limited resource. Excision of burn wounds often leads to significant blood loss requiring transfusion. Accurately estimating blood loss is difficult, so examining the amount of blood products given intraoperatively is a clinically relevant way to measure utilization of this valuable resource. In this study, we examined the factors that influenced the amount of blood given intraoperatively during burn wound excisions. STUDY DESIGN AND METHODS: A retrospective analysis of patients admitted to a single burn center over 5 years who underwent excision of their burn wounds and received intraoperative blood products was performed. Patient and burn characteristics as well as pertinent surgical data and laboratory values on the day of surgery and postoperatively were gathered. A linear regression analysis examined factors influencing the number of units of products given and a predictive model was generated. RESULTS: A total of 563 operations performed on 166 patients were included. The amount of burn excised was the most influential variable on the amount of blood products given. Hemoglobin level, international normalized ratio, and platelet count on the day of surgery were associated with transfusion of different blood products. A predictive model was generated to aid in preoperative ordering of blood products. CONCLUSION: The amount of burn excised and common hematology and coagulation lab values were associated with the amount of different blood products administered during burn surgery. The predictive model generated needs to be validated prospectively to aid in preoperative planning for burn excisions.


Assuntos
Transfusão de Sangue , Queimaduras/terapia , Adulto , Transfusão de Sangue/métodos , Queimaduras/sangue , Queimaduras/cirurgia , Feminino , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
13.
Transfusion ; 61 Suppl 1: S111-S118, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269464

RESUMO

BACKGROUND: Never frozen liquid plasma (LP) has limited shelf life versus fresh frozen plasma (FFP) or plasma frozen within 24 h (PF24). Previous studies showed decreasing factor activities after Day (D)14 in thawed FFP but no differences between LP and FFP until D10. This study examined LP function through D40. STUDY DESIGN AND METHODS: FFP and PF24 were stored at -20°C until assaying. LP was assayed on D5 then stored (4°C) for testing through D40. A clinical coagulation analyzer measured Factor (F)V, FVIII, fibrinogen, prothrombin time (PT), and activated partial thromboplastin time (aPTT). Thromboelastography (TEG) and thrombogram measured functional coagulation. Ristocetin cofactor assay quantified von Willebrand factor (vWF) activity. Residual platelets were counted. RESULTS: FV/FVIII showed diminished activity over time in LP, while PT and aPTT both increased over time. LP vWF declined significantly by D7. Fibrinogen remained high through D40. Thrombin lagtime was delayed in LP but consistent to D40, while peak thrombin was significantly lower in LP but did not significantly decline over time. TEG R-time and angle remained constant. LP and PF24 (with residual platelets) had initially higher TEG maximum amplitudes (MA), but by D14 LP was similar to FFP. CONCLUSION: Despite significant declines in some factors in D40 LP, fibrinogen concentration and TEG MA were stable suggesting stored LP provides fibrinogen similarly to frozen plasmas even at D40. LP is easier to store and prepare for prehospital transfusion, important benefits when the alternative is crystalloid.


Assuntos
Testes de Coagulação Sanguínea , Coagulação Sanguínea , Preservação de Sangue , Plasma , Criopreservação , Humanos , Tempo de Tromboplastina Parcial , Plasma/metabolismo , Tempo de Protrombina , Temperatura , Tromboelastografia
14.
Transfusion ; 61 Suppl 1: S195-S205, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269466

RESUMO

BACKGROUND: Several tools have been proven to predict the need for massive transfusion in trauma casualties, yet tools that are easily applicable in the prehospital setting for predicting the need for any blood product transfusion in the emergency department (ED) are lacking. METHODS: A retrospective analysis of the cross-referenced Israeli Defense Forces Trauma Registry and the Israeli National Trauma Registry databases was performed to identify predictors for any blood product transfusion in the ED. A scoring system was developed after internally validating the prediction model. Division to risk groups was performed. RESULTS: Seven variables (systolic blood pressure, heart rate, arterial oxygen saturation, trunk involvement, mechanism of injury, chest decompression, and tourniquet application) were included in the scoring system, ranging from 0 to 11.5. Risk groups for ED transfusion included very low (0.8%), low (3.2%), intermediate (8.5%), and high (31.2%) risk. CONCLUSION: A scoring system for predicting the need for any blood product transfusion in the ED was developed, based on information readily available in the early stages of prehospital resuscitation, allowing the receiving medical facility to prepare for that need.


Assuntos
Transfusão de Sangue , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/terapia , Adolescente , Adulto , Idoso , Serviços Médicos de Emergência , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Prognóstico , Ressuscitação , Estudos Retrospectivos , Adulto Jovem
15.
J Trauma Acute Care Surg ; 91(2S Suppl 2): S81-S88, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34108422

RESUMO

BACKGROUND: Extracellular vesicles (EVs) isolated from cardiosphere-derived cells (CDC-EVs) are coming to light as a unique cell-free therapeutic. Because of their novelty, however, there still exist prominent gaps in knowledge regarding their therapeutic potential. Herein the therapeutic potential of CDC-EVs in a rat model of acute traumatic coagulopathy induced by multiple injuries and hemorrhagic shock is outlined. METHODS: Extracellular vesicle surface expression of procoagulant molecules (tissue factor and phosphatidylserine) was evaluated by flow cytometry. Extracellular vesicle thrombogenicity was tested using calibrated thrombogram, and clotting parameters were assessed using a flow-based adhesion model simulating blood flow over a collagen-expressing surface. The therapeutic efficacy of EVs was then determined in a rat model of acute traumatic coagulopathy induced by multiple injuries and hemorrhagic shock. RESULTS: Extracellular vesicles isolated from cardiosphere-derived cells are not functionally procoagulant and do not interfere with platelet function. In a rat model of multiple injuries and hemorrhagic shock, early administration of EVs significantly reduced the elevation of lactate and creatinine and did not significantly enhance coagulopathy in rats with acute traumatic coagulopathy. CONCLUSION: The results of this study are of great relevance to the development of EV products for use in combat casualty care, as our studies show that CDC-EVs have the potential to be an antishock therapeutic if administered early. These results demonstrate that research using CDC-EVs in trauma care needs to be considered and expanded beyond their reported cardioprotective benefits.


Assuntos
Vesículas Extracelulares/transplante , Traumatismo Múltiplo/terapia , Miocárdio/citologia , Choque Hemorrágico/terapia , Animais , Glicemia/análise , Creatinina/sangue , Modelos Animais de Doenças , Citometria de Fluxo , Escala de Gravidade do Ferimento , Ácido Láctico/sangue , Masculino , Tempo de Protrombina , Ratos , Ratos Sprague-Dawley
16.
J Trauma Acute Care Surg ; 91(2S Suppl 2): S182-S185, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33951026

RESUMO

ABSTRACT: Before death, patients commonly experience impaired consciousness for a significant period, frequently preventing family and others from final interactions with the patient. Some of these episodes of cognitive impairment may be treatable, with treatment not offered owing to the perception of ultimate futility or expense, or both. One of the causes of terminal loss of consciousness or decreased lucidity can be inadequate cerebral oxygen delivery. We report five cases from four institutions where an infusion of a hemoglobin-based oxygen carrier to patients who were unconscious or not lucid owing to acute severe anemia (hemoglobin range, 2.1-5.2 g/dL) resulted in awakening or lucidity. We review briefly human cognitive function and anemia and remark about the use of a hemoglobin-based oxygen carrier for acute severe anemia when red cell transfusion is not an option.


Assuntos
Anemia/complicações , Substitutos Sanguíneos/uso terapêutico , Disfunção Cognitiva/prevenção & controle , Idoso de 80 Anos ou mais , Anemia/tratamento farmacológico , Disfunção Cognitiva/etiologia , Estado de Consciência/efeitos dos fármacos , Feminino , Hemoglobinas/uso terapêutico , Humanos
17.
J Trauma Acute Care Surg ; 91(2S Suppl 2): S19-S25, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34039915

RESUMO

ABSTRACT: High-quality evidence guiding optimal transfusion and other supportive therapies to reduce bleeding is needed to improve outcomes for patients with either severe bleeding or hemostatic disorders that are associated with poor outcomes. Alongside challenges in performing high-quality clinical trials in patient populations who are at risk of bleeding or who are actively bleeding, the interpretation of research evaluating hemostatic agents has been limited by inconsistency in the choice of primary trial outcomes. This lack of standardization of primary endpoints or outcomes decreases the ability of clinicians to assess the validity of endpoints and compare research results across studies, impairs meta-analytic efforts, and, ultimately, delays the translation of research results into clinical practice. To address this challenge, an international panel of experts was convened by the National Heart Lung and Blood Institute and the US Department of Defense on September 23 and 24, 2019, to develop expert opinion, consensus-based recommendations for primary clinical trial outcomes for pivotal trials in pediatric and adult patients with six categories in various clinical settings. This publication documents the conference proceedings from the workshop funded by the National Heart Lung and Blood Institute and the US Department of Defense that consolidated expert opinion regarding clinically meaningful outcomes across a wide range of disciplines to provide guidance for outcomes of future trials of hemostatic products and agents for patients with active bleeding.


Assuntos
Hemorragia/tratamento farmacológico , Hemostáticos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Perda Sanguínea Cirúrgica/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Determinação de Ponto Final/normas , Hemorragia Gastrointestinal/tratamento farmacológico , Hemofilia A/tratamento farmacológico , Hemorragia/etiologia , Humanos , Hemorragias Intracranianas/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Resultado do Tratamento , Ferimentos e Lesões/complicações
18.
J Trauma Acute Care Surg ; 91(2S Suppl 2): S65-S73, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34039924

RESUMO

BACKGROUND: We sought to determine the extent of loss of endothelial basement membrane (BM), leukocyte recruitment, and changes in coagulation after hemorrhagic shock, followed by limited-volume resuscitation (LVR) with 5% albumin (ALB). METHODS: Anesthetized rats were bled 40% of blood volume and assigned to treatment groups: untreated (n = 6), LVR with normal saline (NS; n = 8), or LVR with ALB (n = 8). Sham rats (n = 6) underwent all procedures except hemorrhage or resuscitation. Blood samples were assayed for active proteases, such as metalloproteinase 9 (MMP-9) and a disintegrin and metalloproteinase 10 (ADAM-10), BM-type heparan sulfate proteoglycan (perlecan), cell count, and coagulation function. Leukocyte transmigration was used to estimate the net efficiency of leukocyte recruitment in cremaster venules. RESULTS: Hemorrhage significantly lowered red cell count, but white cell and platelet counts did not change (vs. sham). Ionized calcium in plasma was significantly reduced in untreated and remained so after NS. In contrast, ionized calcium was normalized after ALB. Plasma expansion after NS and ALB further reduced leukocyte and platelet counts. Metalloproteinase 9, ADAM-10, and perlecan were significantly higher in untreated rats (vs. sham). Albumin normalized MMP-9, ADAM-10, and perlecan levels, while NS further increased MMP-9, ADAM-10, and perlecan (vs. sham). Transmigrated leukocytes doubled in the untreated group and remained elevated after NS (vs. sham) but normalized after ALB. Albumin reduced every stage of the leukocyte recruitment process to sham levels. CONCLUSION: Despite similar plasma expansion, NS weakened platelet function contrary to ALB. Plasma expansion with ALB resulted in restoration of BM integrity and attenuation of leukocyte recruitment to tissues, in contrast to NS. Albumin plays a critical role in restoring BM integrity, attenuating leukocyte recruitment to tissues, and optimizing hemostasis by increasing ionized calcium in plasma.


Assuntos
Albuminas/uso terapêutico , Membrana Basal/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Choque Hemorrágico/metabolismo , Animais , Membrana Basal/metabolismo , Membrana Basal/fisiopatologia , Contagem de Células Sanguíneas , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Hemostasia/fisiologia , Leucócitos/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Ressuscitação/métodos , Choque Hemorrágico/patologia , Choque Hemorrágico/terapia
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