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1.
Intensive Care Med ; 47(4): 422-434, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33713156

RESUMO

PURPOSE: Most randomized controlled trials (RCTs) in patients with acute respiratory distress syndrome (ARDS) revealed indeterminate or conflicting study results. We aimed to systematically evaluate between-trial heterogeneity in reporting standards and trial outcome. METHODS: A systematic review of RCTs published between 2000 and 2019 was performed including adult ARDS patients receiving lung-protective ventilation. A random-effects meta-regression model was applied to quantify heterogeneity (non-random variability) and to evaluate trial and patient characteristics as sources of heterogeneity. RESULTS: In total, 67 RCTs were included. The 28-day control-group mortality rate ranged from 10 to 67% with large non-random heterogeneity (I2 = 88%, p < 0.0001). Reported baseline patient characteristics explained some of the outcome heterogeneity, but only six trials (9%) reported all four independently predictive variables (mean age, mean lung injury score, mean plateau pressure and mean arterial pH). The 28-day control group mortality adjusted for patient characteristics (i.e. the residual heterogeneity) ranged from 18 to 45%. Trials with significant benefit in the primary outcome reported a higher control group mortality than trials with an indeterminate outcome or harm (mean 28-day control group mortality: 44% vs. 28%; p = 0.001). CONCLUSION: Among ARDS RCTs in the lung-protective ventilation era, there was large variability in the description of baseline characteristics and significant unexplainable heterogeneity in 28-day control group mortality. These findings signify problems with the generalizability of ARDS research and underline the urgent need for standardized reporting of trial and baseline characteristics.

2.
Thromb Res ; 199: 143-148, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33535120

RESUMO

INTRODUCTION: In the first wave, thrombotic complications were common in COVID-19 patients. It is unknown whether state-of-the-art treatment has resulted in less thrombotic complications in the second wave. METHODS: We assessed the incidence of thrombotic complications and overall mortality in COVID-19 patients admitted to eight Dutch hospitals between September 1st and November 30th 2020. Follow-up ended at discharge, transfer to another hospital, when they died, or on November 30th 2020, whichever came first. Cumulative incidences were estimated, adjusted for competing risk of death. These were compared to those observed in 579 patients admitted in the first wave, between February 24th and April 26th 2020, by means of Cox regression techniques adjusted for age, sex and weight. RESULTS: In total 947 patients with COVID-19 were included in this analysis, of whom 358 patients were admitted to the ICU; 144 patients died (15%). The adjusted cumulative incidence of all thrombotic complications after 10, 20 and 30 days was 12% (95% confidence interval (CI) 9.8-15%), 16% (13-19%) and 21% (17-25%), respectively. Patient characteristics between the first and second wave were comparable. The adjusted hazard ratio (HR) for overall mortality in the second wave versus the first wave was 0.53 (95%CI 0.41-0.70). The adjusted HR for any thrombotic complication in the second versus the first wave was 0.89 (95%CI 0.65-1.2). CONCLUSIONS: Mortality was reduced by 47% in the second wave, but the thrombotic complication rate remained high, and comparable to the first wave. Careful attention to provision of adequate thromboprophylaxis is invariably warranted.


Assuntos
/complicações , Embolia Pulmonar/etiologia , Trombose/etiologia , Tromboembolia Venosa/etiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estado Terminal/mortalidade , Feminino , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Modelos de Riscos Proporcionais , /isolamento & purificação
3.
Intensive Care Med ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048195

RESUMO

PURPOSE: Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs). METHODS: This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI). RESULTS: Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76-1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54-1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84-5.34). CONCLUSION: There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols.

4.
Transfus Clin Biol ; 26(1): 10-17, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30686333

RESUMO

OBJECTIVE: To investigate the relation between donor characteristics and TRALI incidence. BACKGROUND: Transfusion-related acute lung injury (TRALI) is a potentially fatal complication of transfusion. In pre-clinical studies and several clinical studies, TRALI has been related to loss of product quality during red blood cell (RBC) storage, called the "storage lesion". Donor characteristics, as for example age, genetics and life style choices influence this "storage lesion". We hypothesized that donor sex, age and blood type is related to TRALI incidence. METHODS/MATERIALS: We performed a secondary analysis of two cohort studies, designed to identify TRALI risk factors by matching TRALI patients to transfused controls. We obtained donor sex, age and blood type from the Dutch Blood Bank Sanquin and investigated TRALI incidence in patients who were exposed to a certain donor characteristic. We used Kruskal-Wallis testing to compare the number of transfused products and Chi2 testing to compare proportions of TRALI patients and transfused control. RESULTS: After implementation of the male-donor only plasma strategy, patients received more transfusion products from male donors. However, we did not detect a relation between TRALI incidence and donor sex. Both TRALI patients and transfused controls received mainly products from donors over 41 years old, but donor age did not influence TRALI risk. Donor blood type, the transfusion of blood type-compatible and blood type-matched products also had no influence on TRALI incidence. CONCLUSION: We conclude that in two cohorts of TRALI patients, donor age, donor sex and donor blood type are unrelated to TRALI.


Assuntos
Doadores de Sangue/estatística & dados numéricos , Lesão Pulmonar Aguda Relacionada à Transfusão/epidemiologia , Adolescente , Adulto , Idoso , Antígenos de Grupos Sanguíneos/efeitos adversos , Transfusão de Sangue , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Lesão Pulmonar Aguda Relacionada à Transfusão/etiologia , Adulto Jovem
5.
Crit Care ; 22(1): 243, 2018 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-30268133

RESUMO

BACKGROUND: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) reduce colonization with antibiotic-resistant Gram-negative bacteria (ARGNB), incidence of nosocomial infections and improve survival in ICU patients. The effect on bacterial gut colonization might be caused by growth suppression by antibiotics during SDD/SOD. We investigated intestinal colonization with ARGNB after discharge from ICU and discontinuation of SDD or SOD. METHODS: We performed a prospective, observational follow-up study in regular hospital wards of three teaching hospitals in the Netherlands in patients discharged from the ICU, who were participating in a cluster randomized trial comparing SDD with SOD. We determined rectal carriage with ARGNB at ICU discharge (time (T) = 0) and 3, 6 and 10 days after discharge. The primary endpoint was time to first colonization with ARGNB that was not present at T = 0. Bacteria that are intrinsically resistant to antibiotics were not included in the primary analysis, but were included in post-hoc analysis. RESULTS: Of 1370 patients screened for inclusion, 996 patients had samples at T = 0 (507 after SDD and 489 after SOD). At ICU discharge, the prevalence of intestinal carriage with any ARGNB was 22/507 (4.3%) after SDD and 87/489 (17.8%) after SOD (p < 0.0001): 426 (SDD) and 409 (SOD) patients had at least one follow-up sample for analysis. The hazard rate for acquiring carriage of ARGNB after discontinuation of SDD, compared to SOD, in the ICU was 0.61 (95% CI 0.40-0.91, p = 0.02), and cumulative risks of acquisition of at least one ARGNB until day 10 were 13% (SDD) and 18% (SOD). At day 10 after ICU discharge, the prevalence of intestinal carriage with ARGNB was 11.3% (26/230 patients) after SDD and 12.5% (28/224 patients) after SOD (p = 0.7). In post-hoc analysis of all ARGNB, including intrinsically resistant bacteria, colonization at ICU discharge was lower after SDD (4.9 vs. 22.3%, p < 0.0001), but acquisition rates after ICU discharge were similar in both groups. CONCLUSIONS: Intestinal carriage at ICU discharge and the acquisition rate of ARGNB after ICU discharge are lower after SDD than after SOD. The prevalence of intestinal carriage with ARGNB at 10 days after ICU discharge was comparable in both groups, suggesting rapid clearance of ARGNB from the gut after ICU discharge. TRIAL REGISTRATION: Netherlands Trial Registry, NTR3311 . Registered on 28 february 2012.


Assuntos
Descontaminação/métodos , Bactérias Gram-Negativas/efeitos dos fármacos , Adulto , Idoso , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Seguimentos , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/fisiopatologia , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Países Baixos , Orofaringe/efeitos dos fármacos , Orofaringe/microbiologia , Estudos Prospectivos
6.
Blood Rev ; 31(6): 400-405, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28755795

RESUMO

As the main iron transporter, transferrin delivers iron to target tissues like the bone marrow for erythropoiesis. Also, by binding free iron, transferrin prevents formation of reactive oxygen species. Transferrin deficiency due to congenital hypotransferrinemia is characterized by anemia as well as oxidative stress related to toxic free iron. Transferrin supplementation may be beneficial in two ways. First, transferrin can correct anemia by modulating the amount of iron that is available for erythropoiesis. This is obvious for patients that suffer from hypotransferrinemia, but may also have beneficial effects for ß-thalassemia patients. Second, under conditions of iron overload, transferrin reduces oxidative stress by binding free iron in the circulation and in tissues. Hereby, transferrin protects the host against the reactive oxygen species that can be formed as a consequence of free iron. This beneficial effect is shown in hematological patients undergoing chemotherapy and stem cell transplantation. Transferrin may also be beneficial in lung injury, ischemia-reperfusion injury and hypomyelination. This review summarizes the preclinical and clinical data on the efficacy of exogenous transferrin administration to modulate certain forms of anemia and to prevent the toxic effects of free iron. Thereby, we show that transferrin has promising therapeutic potential in a wide variety of conditions.


Assuntos
Anemia/tratamento farmacológico , Transferrina/uso terapêutico , Anemia/metabolismo , Animais , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/metabolismo , Humanos , Hiperóxia/tratamento farmacológico , Hiperóxia/metabolismo , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/metabolismo , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/metabolismo , Degeneração Macular/tratamento farmacológico , Degeneração Macular/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Transplante de Células-Tronco/métodos , Talassemia beta/tratamento farmacológico , Talassemia beta/metabolismo
7.
Br J Surg ; 104(3): 222-229, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28079258

RESUMO

BACKGROUND: The combined effects of balanced transfusion ratios and use of procoagulant and antifibrinolytic therapies on trauma-induced exsanguination are not known. The aim of this study was to investigate the combined effect of transfusion ratios, tranexamic acid and products containing fibrinogen on the outcome of injured patients with bleeding. METHODS: A prospective multicentre observational study was performed in six level 1 trauma centres. Injured patients who received at least 4 units of red blood cells (RBCs) were analysed and divided into groups receiving a low (less than 1 : 1) or high (1 or more : 1) ratio of plasma or platelets to RBCs, and in receipt or not of tranexamic acid or fibrinogen products (fibrinogen concentrates or cryoprecipitate). Logistic regression models were used to assess the effect of transfusion strategies on the outcomes 'alive and free from massive transfusion' (at least 10 units of RBCs in 24 h) and early 'normalization of coagulopathy' (defined as an international normalized ratio of 1·2 or less). RESULTS: A total of 385 injured patients with ongoing bleeding were included in the study. Strategies that were independently associated with an increased number of patients alive and without massive transfusion were a high platelet to RBC ratio (odds ratio (OR) 2·67, 95 per cent c.i. 1·24 to 5·77; P = 0·012), a high plasma to RBC ratio (OR 2·07, 1·03 to 4·13; P = 0·040) and treatment with tranexamic acid (OR 2·71, 1·29 to 5·71; P = 0·009). No strategies were associated with correction of coagulopathy. CONCLUSION: A high platelet or plasma to RBC ratio, and use of tranexamic acid were associated with a decreased need for massive transfusion and increased survival in injured patients with bleeding. Early normalization of coagulopathy was not seen for any transfusion ratio, or for use of tranexamic acid or fibrinogen products.


Assuntos
Antifibrinolíticos/uso terapêutico , Transtornos da Coagulação Sanguínea/terapia , Transfusão de Sangue/métodos , Hemorragia/terapia , Hemostáticos/uso terapêutico , Ferimentos e Lesões/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/mortalidade , Terapia Combinada , Feminino , Fibrinogênio/uso terapêutico , Hemorragia/etiologia , Hemorragia/mortalidade , Humanos , Coeficiente Internacional Normatizado , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ácido Tranexâmico/uso terapêutico , Resultado do Tratamento , Ferimentos e Lesões/mortalidade
9.
Intensive Care Med Exp ; 3(1): 27, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26384491

RESUMO

BACKGROUND: Animal models are valuable in transfusion research. Use of human red blood cells (RBCs) in animal models facilitates extrapolation of the impact of storage conditions to the human condition but may be hampered by the use of cross species. METHODS: Investigation of clearance and posttransfusion recovery in a rat model using fresh and stored human RBCs. RESULTS: Directly following transfusion, human RBCs could be detected in the circulation of all recipients, with higher recovery rates for stored RBCs than for fresh RBCs. After 24 h following transfusion, no donor RBCs could be detected in the circulation, but donor RBCs could be detected in all organs of all recipients. CONCLUSION: The use of human donor RBCs in a rat transfusion model resulted in clearance from cells from the circulation. Donor cells were found in different organs of the recipients. Rat transfusion models are thus not appropriate to study the efficacy of human RBC transfusion.

11.
J Thromb Haemost ; 13(6): 989-97, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25809519

RESUMO

BACKGROUND: Coagulopathy has a high prevalence in critically ill patients. An increased International Normalized Ratio (INR) is a common trigger to transfuse fresh frozen plasma (FFP), even in the absence of bleeding. Therefore, FFP is frequently administered to these patients. However, the efficacy of FFP in correcting hemostatic disorders in non-bleeding recipients has been questioned. OBJECTIVES: To assess whether INR prolongation parallels changes in the results of other tests investigating hemostasis, and to evaluate the coagulant effects of a fixed dose of FFP in non-bleeding critically ill patients with a coagulopathy. METHODS: Markers of coagulation, individual factor levels and levels of natural anticoagulants were measured. Also, thrombin generation and thromboelastometry (ROTEM) assays were performed before and after FFP transfusion (12 mL kg(-1) ) to 38 non-bleeding critically ill patients with an increased INR (1.5-3.0). RESULTS: At baseline, levels of factor II, FV, FVII, protein C, protein S and antithrombin were reduced, and thrombin generation was impaired. ROTEM variables were within reference ranges, except for a prolonged INTEM clot formation time. FFP transfusion increased the levels of coagulation factors (FII, 34% [interquartile range (IQR) 26-46] before vs. 44% [IQR 38-52] after; FV, 48% [IQR 28-76] before vs. 58% [IQR 44-90] after; and FVII, 25% [IQR 16-38] before vs. 37% [IQR 28-55] after), and the levels of anticoagulant proteins. Thrombin generation was unaffected by FFP transfusion (endogenous thrombin potential, 72% [IQR 51-88] before vs. 71% [IQR 42-89] after), whereas ROTEM EXTEM clotting time and maximum clot firmness slightly improved in response to FFP. CONCLUSION: In non-bleeding critically ill patients with a coagulopathy, FFP transfusion failed to induce a more procoagulant state.


Assuntos
Transtornos da Coagulação Sanguínea/terapia , Transfusão de Componentes Sanguíneos/métodos , Hemostasia , Plasma , Idoso , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Transfusão de Componentes Sanguíneos/efeitos adversos , Estado Terminal , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Países Baixos , Tempo de Tromboplastina Parcial , Valor Preditivo dos Testes , Tempo de Protrombina , Falha de Tratamento
12.
Transfus Med ; 24(5): 292-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25202858

RESUMO

BACKGROUND: Prophylactic use of fresh frozen plasma (FFP) in critically ill patients with a coagulopathy is common. However, a lack of evidence of efficacy has resulted in a call for trials on the benefit of FFP in these patients. To date, conducting a trial on this subject has not been successful. Recently, a multi-center randomised trial was stopped prematurely due to slow inclusion. OBJECTIVE: To assess clinicians' opinions regarding a trial on prophylactic administration of FFP in coagulopathic critically ill patients who need to undergo an intervention. METHODS: A survey among 55 intensivists who all participated in a randomised trial on the risks and benefits of FFP in critically ill patients. RESULTS: Response rate was 84%. Majority of respondents indicated that international normalised ratio (INR) should be assessed before insertion of a central venous catheter (CVC) (61%), chest tube (89%) or tracheostomy (91%). Reasons to withhold transfusion of FFP to non-bleeding critically ill patients are risk of transfusion-related acute lung injury (TRALI) (46%), fluid overload (39%) and allergic reaction (24%). Although, the majority of respondents expressed the opinion that the trial was clinically relevant, 56% indicated that ≥1 patient subgroups should have been excluded from participation. CONCLUSION: Intensivists express the need for more evidence on the prophylactic use of FFP in coagulopathic critically ill patients. However, lack of knowledge about FFP and personal beliefs about the preferable transfusion strategy among clinicians, resulted in premature termination of a clinical trial on this topic.


Assuntos
Transtornos da Coagulação Sanguínea/prevenção & controle , Transfusão de Componentes Sanguíneos/métodos , Aceitação pelo Paciente de Cuidados de Saúde , Plasma , Inquéritos e Questionários , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/etiologia , Adulto , Idoso , Transtornos da Coagulação Sanguínea/sangue , Transfusão de Componentes Sanguíneos/efeitos adversos , Estado Terminal , Feminino , Humanos , Coeficiente Internacional Normatizado/métodos , Masculino , Pessoa de Meia-Idade
13.
Cell Biochem Biophys ; 70(2): 795-803, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24760631

RESUMO

Mechanical ventilation has the potential to cause lung injury, and the role of complement activation herein is uncertain. We hypothesized that inhibition of the complement cascade by administration of plasma-derived human C1-esterase inhibitor (C1-INH) prevents ventilation-induced pulmonary complement activation, and as such attenuates lung inflammation and lung injury in a rat model of Streptococcus pneumoniae pneumonia. Forty hours after intratracheal challenge with S. pneumoniae causing pneumonia rats were subjected to ventilation with lower tidal volumes and positive end-expiratory pressure (PEEP) or high tidal volumes without PEEP, after an intravenous bolus of C1-INH (200 U/kg) or placebo (saline). After 4 h of ventilation blood, broncho-alveolar lavage fluid and lung tissue were collected. Non-ventilated rats with S. pneumoniae pneumonia served as controls. While ventilation with lower tidal volumes and PEEP slightly amplified pneumonia-induced complement activation in the lungs, ventilation with higher tidal volumes without PEEP augmented local complement activation more strongly. Systemic pre-treatment with C1-INH, however, failed to alter ventilation-induced complement activation with both ventilation strategies. In accordance, lung inflammation and lung injury were not affected by pre-treatment with C1-INH, neither in rats ventilated with lower tidal volumes and PEEP, nor rats ventilated with high tidal volumes without PEEP. Ventilation augments pulmonary complement activation in a rat model of S. pneumoniae pneumonia. Systemic administration of C1-INH, however, does not attenuate ventilation-induced complement activation, lung inflammation, and lung injury.


Assuntos
Ativação do Complemento/efeitos dos fármacos , Proteína Inibidora do Complemento C1/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pneumonia/terapia , Respiração Artificial/efeitos adversos , Streptococcus pneumoniae/fisiologia , Animais , Modelos Animais de Doenças , Humanos , Pulmão/microbiologia , Masculino , Ratos , Ratos Wistar , Fatores de Tempo , Lesão Pulmonar Induzida por Ventilação Mecânica/etiologia , Lesão Pulmonar Induzida por Ventilação Mecânica/imunologia , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle
14.
Vox Sang ; 107(1): 71-5, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24372323

RESUMO

BACKGROUND AND OBJECTIVE: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Specific therapy is lacking. We assessed whether C1-inhibitor attenuates lung injury in a 'two-hit' TRALI model. METHODS: Mice were primed with lipopolysaccharide, subsequently TRALI was induced by MHC-I antibodies. In the intervention group, C1-inhibitor was infused concomitantly. Mice were supported with mechanical ventilation. After 2 h, mice were killed, lungs were removed and bronchoalveolar lavage fluid (BALF) was obtained. RESULTS: Injection of MHC-I antibodies induced TRALI, illustrated by an increase in wet-to-dry ratio of the lungs, in BALF protein levels and in lung injury scores. TRALI was further characterized by complement activation, demonstrated by increased BALF levels of C3a and C5a. Administration of C1-inhibitor resulted in increased pulmonary C1-inhibitor levels with high activity. C1-inhibitor reduced pulmonary levels of complement C3a associated with improved lung injury scores. However, levels of pro-inflammatory mediators were unaffected. CONCLUSION: In a murine model of TRALI, C1-inhibitor attenuated pulmonary levels of C3a associated with improved lung injury scores, but with persistent high levels of inflammatory cytokines.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Proteína Inibidora do Complemento C1/administração & dosagem , Reação Transfusional , Reação Transfusional/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/patologia , Análise de Variância , Animais , Anticorpos/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Ativação do Complemento/imunologia , Complemento C3a/imunologia , Complemento C5a/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Lipopolissacarídeos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Reação Transfusional/patologia
16.
Crit Care Res Pract ; 2012: 720950, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22701787

RESUMO

Purpose. Onset of transfusion-related acute lung injury (TRALI) is suggested to be a threshold-event. Data is lacking on the relation between titer of antibodies infused and onset of TRALI. We determined whether onset of TRALI is dependent on the titer of MHC-I antibodies infused in a combined model of ventilator-induced lung injury and antibody-induced TRALl. Methods. BALB/c mice were ventilated for five hours with low (7.5 ml/kg) or high (15 ml/kg) tidal volume. After three hours of MV, TRALI was induced by infusion of 0.5 mg/kg, 2.0 mg/kg or 4.5 mg/kg MHC-I antibodies. Control animals received vehicle. After five hours of MV, animals were sacrificed. Results. MV with high tidal volumes resulted in increased levels of all markers of lung injury compared to animals ventilated with low tidal MV. In ventilator-induced lung injury, infusion of 4.5 mg/kg of antibodies further increased pulmonary wet-to-dry ratio, pulmonary neutrophil influx and pulmonary KC levels, whereas infusion of lower dose of antibodies did not augment lung injury. In contrast, mice ventilated with low tidal volumes did not develop lung injury, irrespective of the dose of antibody used. Conclusions. In the presence of injurious MV, onset of TRALI depends on the titer of antibodies infused.

17.
Anaesthesia ; 67(6): 594-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22324349

RESUMO

Aspirin has been found to improve outcomes in an animal model of transfusion-related acute lung injury. We examined the association of aspirin use before admission to the intensive care unit and the development of transfusion-related acute lung injury in critically ill patients. We performed a post-hoc analysis of a nested case-control study that had been undertaken in a tertiary referral hospital. Transfusion-related acute lung injury cases were matched with controls (transfused patients not developing lung injury). Of these 218 patients, 66 used aspirin (30%). Use of aspirin did not alter the risk of transfusion-related acute lung injury after transfusion of platelets (OR 1.06, CI 0.59-1.91, p = 0.85), plasma (OR 1.06, 95% CI 0.59-1.92, p = 0.84), or red blood cells (OR 1.09, 95% CI 0.61-1.94, p = 0.77). Adjustment for confounding variables using propensity scoring also did not affect the risk of acquiring transfusion-related acute lung injury (p = 0.66). In conclusion, aspirin did not protect against transfusion-related lung injury in this cohort of critically ill patients.


Assuntos
Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/prevenção & controle , Aspirina/uso terapêutico , Estado Terminal/terapia , Inibidores da Agregação de Plaquetas/uso terapêutico , Reação Transfusional , APACHE , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Cuidados Críticos , Transfusão de Eritrócitos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Plasma , Transfusão de Plaquetas/efeitos adversos , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Medição de Risco
18.
Clin Exp Immunol ; 165(2): 278-84, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21605114

RESUMO

Activated platelets have been implicated in playing a major role in transfusion-related acute lung injury (TRALI), as platelets can trigger neutrophils, resulting in vascular damage. We hypothesized that binding of platelet CD40 ligand (CD40L) to endothelial CD40 is essential in the onset of TRALI. Mice were challenged with monoclonal major histocompatibility complex (MHC)-1 antibody which induced TRALI, evidenced by pulmonary oedema, accompanied by significantly elevated bronchoalveolar fluid (BALF) levels of total protein and elevated plasma levels of keratinocyte-derived chemokine (KC) and macrophage inflammatory protein-2 (MIP-2) compared to infusion of isotype antibody (all Ps < 0·05). Treatment with ciglitazone, which inhibits platelet CD40L expression, had no effect on pulmonary and systemic inflammation compared to controls. In addition, treatment with anti-CD40L antibody, which antagonizes all CD40-CD40L interactions, also did not abrogate the TRALI reaction. Furthermore, levels of soluble CD40L were measured in a cohort of cardiac surgery patients, who were followed prospectively for the onset of TRALI after transfusion. Plasma levels of sCD40L at baseline and at time of developing TRALI did not differ between TRALI patients and controls (transfused cardiac surgery patients not developing acute lung injury) (275 ± 192 versus 258 ± 346 and 93 ± 82 versus 93 ± 123 pg/ml, respectively, not significant). In conclusion, these results do not support the idea that the CD40-CD40L interaction is involved in mediating TRALI.


Assuntos
Lesão Pulmonar Aguda/imunologia , Antígenos CD40/metabolismo , Ligante de CD40/metabolismo , Reação Transfusional , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Monoclonais/imunologia , Plaquetas/efeitos dos fármacos , Plaquetas/imunologia , Plaquetas/metabolismo , Líquido da Lavagem Broncoalveolar , Antígenos CD40/imunologia , Ligante de CD40/sangue , Ligante de CD40/genética , Quimiocina CXCL2/sangue , Quimiocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Genes MHC Classe I , Humanos , Inflamação/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Ativação Plaquetária/imunologia , Tiazolidinedionas/farmacologia
19.
Clin Lab ; 57(3-4): 267-72, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21500739

RESUMO

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion related morbidity and mortality. TRALI is suggested to be a "two hit" event. The "first hit" is the underlying condition of the patient which results in sequestration and priming of neutrophils in the pulmonary compartment. The "second hit" is the transfusion of either human leukocyte antibodies or aged blood products which results in activation of the primed neutrophils and finally in pulmonary edema. The present review focuses on pre-clinical studies investigating the role of blood products containing aged cells (red blood cells, RBCs, and platelet concentrates, PLTs) and the onset of TRALI. Several mechanisms are under scrutiny. The first suggested mechanism is that soluble mediators accumulating during storage of RBCs and PLTs may play a role, including bio-active lipids or soluble CD40L. These soluble factors were found to cause lung injury in the presence of a "first hit". Another proposed mechanism involves the aged erythrocyte itself. During storage, the erythrocyte undergoes numerous changes in its biochemical and structural condition and acquires pro-inflammatory properties, sometimes collectively referred to as the "red cell storage lesion". Although it could be speculated that all of these factors may be involved in the onset of TRALI, only one pre-clinical study shows an association between the aged erythrocyte and the onset of TRALI. The suggested mechanism is a decrease in the chemokine scavenging function of the erythrocyte by reduction of the Duffy antigen expression resulting in an increase in lung injury. Further research is needed to elucidate possible mechanisms of onset of TRALI by aged blood products.


Assuntos
Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/fisiopatologia , Reação Transfusional , Humanos , Fatores de Tempo
20.
Neth J Med ; 68(5): 190-8, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20508267

RESUMO

Induced hypothermia after cardiopulmonary resuscitation provides organ protection and is currently considered standard of care in clinical practice. An increasing number of reports indicate that induced hypothermia is also beneficial in other conditions of hypoxia-induced organ injury, including brain injury, intestinal ischaemia-reperfusion injury and acute lung injury. The mechanism of the protective effect is thought to be caused by a reduction in metabolism. A hibernation-like state, characterised by hypothermia, bradypnoea and a reduction in metabolic rate, was induced in animals that normally do not hibernate, after inhalation of hydrogen sulphide. This state was termed a 'suspended animation-like state'. In critically ill patients, an exaggerated systemic inflammatory response is common, which often results in multiple organ injury. Inducing a hypometabolic state during critical illness may limit organ injury by reducing oxygen consumption, constituting a fascinating new therapeutic perspective for the treatment of critically ill patients. In this manuscript, we describe mitochondrial dysfunction during critical illness and preclinical data that suggest a potential therapeutic possibility of lowering metabolism. In addition, we discuss issues that warrant further research before clinical applicability.


Assuntos
Cuidados Críticos/métodos , Hipotermia Induzida , Insuficiência de Múltiplos Órgãos/prevenção & controle , Síndrome de Resposta Inflamatória Sistêmica/terapia , Animais , Humanos , Insuficiência de Múltiplos Órgãos/etiologia , Síndrome de Resposta Inflamatória Sistêmica/complicações
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