Forum for debate: Safety of allogeneic blood transfusion alternatives in the surgical/critically ill patient.

In recent years, several safety alerts have questioned or restricted the use of some pharmacological alternatives to allogeneic blood transfusion in established indications. In contrast, there seems to be a promotion of other alternatives, based on blood products and/or antifibrinolytic drugs, which lack a solid scientific basis. The Multidisciplinary Autotransfusion Study Group and the Anemia Working Group España convened a multidisciplinary panel of 23 experts belonging to different healthcare areas in a forum for debate to: 1) analyze the different safety alerts referred to certain transfusion alternatives; 2) study the background leading to such alternatives, the evidence supporting them, and their consequences for everyday clinical practice, and 3) issue a weighted statement on the safety of each questioned transfusion alternative, according to its clinical use. The members of the forum maintained telematics contact for the exchange of information and the distribution of tasks, and a joint meeting was held where the conclusions on each of the items examined were presented and discussed. A first version of the document was drafted, and subjected to 4 rounds of review and updating until consensus was reached (unanimously in most cases). We present the final version of the document, approved by all panel members, and hope it will be useful for our colleagues.

[The 2013 Seville Consensus Document on alternatives to allogenic blood transfusion. An update on the Seville Document]. / 2013. Documento Sevilla de Consenso sobre Alternativas a la Transfusión de Sangre Alogénica. Actualización del Documento Sevilla.

Since allogeneic blood transfusion (ABT) is not harmless, multiple alternatives to ABT (AABT) have emerged, though there is great variability in their indications and appropriate use. This variability results from the interaction of a number of factors, including the specialty of the physician, knowledge and preferences, the degree of anemia, transfusion policy, and AABT availability. Since AABTs are not harmless and may not meet cost-effectiveness criteria, such variability is unacceptable. The Spanish Societies of Anesthesiology (SEDAR), Hematology and Hemotherapy (SEHH), Hospital Pharmacy (SEFH), Critical Care Medicine (SEMICYUC), Thrombosis and Hemostasis (SETH) and Blood Transfusion (SETS) have developed a Consensus Document for the proper use of AABTs. A panel of experts convened by these 6 Societies have conducted a systematic review of the medical literature and have developed the 2013 Seville Consensus Document on Alternatives to Allogeneic Blood Transfusion, which only considers those AABT aimed at decreasing the transfusion of packed red cells. AABTs are defined as any pharmacological or non-pharmacological measure aimed at decreasing the transfusion of red blood cell concentrates, while preserving patient safety. For each AABT, the main question formulated, positively or negatively, is: « Does this particular AABT reduce the transfusion rate or not?¼ All the recommendations on the use of AABTs were formulated according to the Grades of Recommendation Assessment, Development and Evaluation (GRADE) methodology.

[Treatment alternatives in massive hemorrhage]. / Alternativas terapéuticas de la hemorragia masiva.

Massive hemorrhage is the main cause of mortality and morbidity in trauma patients, and is one of the most important causes in any patient following major surgery. Conventional treatment consists of volume replacement, including the transfusion of blood products, so that tissue perfusion and oxygenation may be maintained. Associated hypothermia, acidosis and coagulopathy is a lethal triad. This review focuses on the latest therapeutic management of massive hemorrhage. The authors advocate the use of crystalloids as per protocol (controlled volumes) in order to achieve a systolic blood pressure of 85mmHg. The administration of the three blood products (red cells, plasma, and platelets) should be on a 1:1:1 basis. Where possible, this in turn should be guided by thromboelastography performed at point of care near the patient. Coagulopathy can occur early and late. With the exception of tranexamic acid, the cost-benefit relationships of the hemostatic agents, such as fibrinogen, prothrombin complex, and recombinant F VII, are subject to discussion.

Fate of rejected manuscripts in the journal Medicina Intensiva during 2015-2017 period.

OBJECTIVE: To know the fate of the rejected manuscripts in Medicina Intensiva journal (MI) from 2015 to 2017 with surveillance until 2019. DESIGN: Retrospective observational study. SETTING: Biomedical journals publication. PARTICIPANTS: Rejected manuscripts in MI journal. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Time of publication, impact factor (IF), generated citations and variables associated to publication. RESULTS: The 69% (420) of analyzed articles (344 originals and 263 scientific letters) were rejected, and 205 (48.8%) were subsequently published, with 180 citations of 66 articles. Journal IF was lower in 173 (84.4%) articles. The number of FI-valid citations was higher than the FI of MI in 21 articles. Origin of manuscript OR 2,11 (IC 95% 1.29-3.46), female author OR 1.58 (IC 95% 1.03-2.44), english language OR 2,38 (IC 95% 1.41-4.0) and reviewed papers OR 1.71 (IC 95% 1.10-2.66) were associated to publication in PubMed database. CONCLUSIONS: The rejected articles in MI have a mean publication rate in other journals. Most of these articles are published in journals with less IF and fewer citations than the IF of MI.

Fate of rejected manuscripts in the journal Medicina Intensiva during 2015-2017 period. / Destino de los artículos rechazados en Medicina Intensiva en el período 2015-2017.

OBJECTIVE: To know the fate of the rejected manuscripts in Medicina Intensiva journal (MI) from 2015 to 2017 with surveillance until 2019. DESIGN: Retrospective observational study. SETTING: Biomedical journals publication. PARTICIPANTS: Rejected manuscripts in MI journal. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Time of publication, impact factor (IF), generated citations and variables associated to publication. RESULTS: The 69% (420) of analyzed articles (344 originals and 263 scientific letters) were rejected, and 205 (48.8%) were subsequently published, with 180 citations of 66 articles. Journal IF was lower in 173 (84.4%) articles. The number of FI-valid citations was higher than the FI of MI in 21 articles. Origin of manuscript OR 2,11 (IC 95% 1.29 - 3.46), female author OR 1.58 (IC 95% 1.03-2.44), english language OR 2,38 (IC 95% 1.41-4.0) and reviewed papers OR 1.71 (IC 95% 1.10-2.66) were associated to publication in PubMed database. CONCLUSIONS: The rejected articles in MI have a mean publication rate in other journals. Most of these articles are published in journals with less IF and fewer citations than the IF of MI.

Transfusion of blood components and postoperative infection in patients undergoing cardiac surgery.

OBJECTIVE: To investigate the influence of blood derivatives on the acquisition of severe postoperative infection (SPI) in patients undergoing heart surgery. SETTING: The postoperative ICUs of a tertiary-level university hospital. DESIGN: A cohort study. METHODS: During a 4-year period, 738 patients, classified as patients with SPIs and patients without SPIs (non-SPI patients), were included in the study. We studied the influence of 36 variables on the development of SPI in general and individually for pneumonia, mediastinitis, and/or septicemia. The influence of the blood derivatives on infections was assessed for RBC concentrates, RBC and plasma, and RBC and platelets. RESULTS: Seventy patients (9.4%) were classified as having SPIs, and 668 (90.6%) were classified as not having SPIs. After multivariate analysis, the variables associated with SPI (incidence, 9.4%) were reintubation, sternal dehiscence, mechanical ventilation (MV) for > or = 48 h, reintervention, neurologic dysfunction, transfusion of > or = 4 U RBCs, and systemic arterial hypotension. The variables associated with nosocomial pneumonia (incidence, 5.9%) were reintubation, MV for > or = 48 h, neurologic dysfunction, transfusion of > or = 4 U blood components, and arterial hypotension. The variables associated with mediastinitis (incidence, 2.3%) were reintervention and sternal dehiscence, and those associated with sepsis (incidence, 1.6%) were reintubation, time of bypass > or = 110 min, and MV for > or = 48 h. The mortality rate (patients with SPI, 52.8%; non-SPI patients, 8.2%; p < 0.001) and mean (+/- SD) length of stay in the ICU (patients with SPI, 15.8 +/- 12.9 days; non-SPI patients, 4.5 +/- 4.4 days; p < 0.001) were greater for the infected patients. The transfused patients also had a greater mortality rate (13.3% vs 8.9%, respectively; p < 0.001) and a longer mean stay in the ICU (6.1 +/- 7.2 days vs 3.7 +/- 2.8 days, respectively; p < 0.01) than those not transfused. CONCLUSION: The administration of blood derivatives, mainly RBCs, was associated in a dose-dependent manner with the development of SPIs, primarily nosocomial pneumonia.

Diagnostic value of the blind brush in mechanically ventilated patients with nosocomial pneumonia.

OBJECTIVES: To check on the accuracy of a new protected blind brush (BB) inserted through an endotracheal tube to collect respiratory secretions to be used in the diagnosis of nosocomial pneumonia (NP) in ventilated patients. DESIGN: Prospective study of patients who had undergone both BB and plugged telescoping catheter via fiberoptic bronchoscopy (PTC-FB) sample collection sessions. SETTING: Intensive Care Unit of a referral-based University Hospital. PATIENTS: All patients (n = 37) mechanically ventilated for more than 3 days with clinical and radiological criteria of NP between July 1990 and March 1991. INTERVENTIONS: Randomized BB and PTC-FB sample collection sessions carried out less than 30 min apart. MEASUREMENTS AND MAIN RESULTS: The two sampling procedures resulted in similar findings with both cultures either negative or positive and identified the same organism and colonies in 31 patients (83.7%). Agreement was 90% when the patients with right or bilateral pulmonary infiltrates were grouped together and 100% when only the right field was considered. Complications arising from BB sampling were much lower than those from the conventional PTC-FB technique. CONCLUSIONS: Our results, pending confirmation by other prospective studies, indicate that BB sampling is useful in the diagnosis of NP in ventilated patients with radiological evidence of either right or bilateral pulmonary infiltrates and that it could stand in for PTC-FB in ICU settings where this procedure is not available.

Do multiple blood transfusions predispose for a higher rate of non-blood-related infection complications?

Allogeneic transfusions of red blood cell (RBC) concentrates have been related to an increase in postoperative infections. Leukocytes present in RBC units might have deleterious effects on the receptor immune system, provoking a state of immunosuppression that favors the development of postoperative infections (TRIM effect). The bioactive substances released by leukocytes in a time-dependent form, accumulating in blood components during storage, might be responsible for the TRIM effect. Multiple observational studies with logistic regression have demonstrated a direct relationship between transfusion and infection. However, several factors related to surgical difficulty and patient illness severity might act as strong confounding variables on the relationship studied. Randomized controlled trials designed to establish a causal relationship between transfusion and infection have yielded contradictory results. While we await new studies, allogeneic transfusions should be considered as a possible risk factor for postoperative infection.

[The hemolytic-uremic syndrome: a report of a case which started as a massive pulmonary hemorrhage]. / Síndrome hemolítico-urémico: presentación de un caso que debutó como hemorragia pulmonar masiva.

Hemolytic-uremic syndrome is a disease of different etiology, characterized by thrombocytopenia, hemolytic anemia and renal failure. A case of lethal evolution that afflicted a 18 year old male is presented. The exceptional presentation with massive pulmonary hemorrhage highlighted.

[2013: The Seville document on consensus on the alternatives to allogenic blood transfusion. Update to the Seville document. Spanish Societies of Anaesthesiology (SEDAR), Haematology and Haemotherapy (SEHH), Hospital Pharmacy (SEFH), Critical Care Medicine (SEMICYUC), Thrombosis and Haemostasis (SETH) and Blood Transfusion (SETS)]. / 2013: Documento «Sevilla¼ de Consenso sobre Alternativas a la Transfusión de Sangre Alogénica. Actualización del Documento Sevilla

As allogeneic blood transfusion (ABT) is not harmless, multiple alternatives to TSA (AABT) have emerged, but there is a huge variability with respect to their indications and appropriate use. This variability results from the interplay of a number of factors, which include physicians specialty, knowledge and preferences, degree of anaemia, transfusion policy, and AABT availability. Since the ABBT are not harmless and may not meet costeffectiveness criteria, such avariability is unacceptable. The Spanish Societies of Anaesthesiology (SEDAR), Haematology and Haemotherapy (SEHH), Hospital Pharmacy (SEFH), Critical Care Medicine (SEMICYUC), Thrombosis and Haemostasis (SETH) and Blood Transfusion (SETS) have developed a Consensus Document for the proper use of AABTs. A panel of experts convened by these six Societies have conducted a systematic review of the medical literature and developed the «2013. Seville Document of Consensus on Alternatives to Allogeneic Blood Transfusion¼, which only considers those AABT aimed to decrease the transfusion of packed red cells. The AABTs are defined as any pharmacological and non-pharmacological measure aimed to decrease the transfusion of of red blood cell concentrates, while preserving the patient safety. For each AABT, the main question is formulated, positively or negatively, as: «Does or does not this particular AABT reduce the transfusion rate?¼ All the recommendations on the use of AABTs were formulated according to the GRADE (Grades of Recommendation Assessment, Development and Evaluation) methodology.

La transfusión de sangre alogénica (TSA) no es inocua, y como consecuencia han surgido múltiples alternativas a la TSA (ATSA). Existe variabilidad respecto a las indicaciones y buen uso de las ATSA. Dependiendo de la especialidad de los médicos que tratan a los pacientes, grado de anemia, política transfusional, disponibilidad de las ATSA y criterio personal, las ATSA se usan de forma variable. Puesto que las ATSA tampoco son inocuas y pueden no cumplir criterios de coste-efectividad, la variabilidad en su uso es inaceptable. Las sociedades españolas de Anestesiología y Reanimación (SEDAR), Hematología y Hemoterapia (SEHH), Farmacia Hospitalaria (SEFH), Medicina Intensiva y Unidades Coronarias (SEMICYUC), Trombosis y Hemostasia (SETH) y Transfusiones Sanguíneas (SETS) han elaborado un documento de consenso para el buen uso de la ATSA. Un panel de expertos de las seis sociedades han llevado a cabo una revisión sistemática de la literatura médica y elaborado el «2013. Documento Sevilla de Consenso sobre Alternativas a la Transfusión de Sangre Alogénica¼. Solo se contempla las ATSA dirigidas a disminuir la transfusión de concentrado de hematíes. Se definen las ATSA como toda medida farmacológica y no farmacológica, encaminada a disminuir la transfusión de concentrado de hematíes, preservando siempre la seguridad del paciente. La cuestión principal que se plantea en cada ítem se formula, en forma positiva o negativa, como: «La ATSA en cuestión reduce / no reduce la Tasa Transfusional¼. Para formular el grado de recomendación se ha usado la metodología GRADE (Grades of Recommendation Assessment, Development and Evaluation).

[The 2013 Seville Consensus Document on alternatives to allogenic blood transfusion. An update on the Seville Document]. / 2013. Documento Sevilla de Consenso sobre Alternativas a la Transfusión de Sangre Alogénica. Actualización del Documento Sevilla.

Since allogeneic blood transfusion (ABT) is not harmless, multiple alternatives to ABT (AABT) have emerged, though there is great variability in their indications and appropriate use. This variability results from the interaction of a number of factors, including the specialty of the physician, knowledge and preferences, the degree of anemia, transfusion policy, and AABT availability. Since AABTs are not harmless and may not meet cost-effectiveness criteria, such variability is unacceptable. The Spanish Societies of Anesthesiology (SEDAR), Hematology and Hemotherapy (SEHH), Hospital Pharmacy (SEFH), Critical Care Medicine (SEMICYUC), Thrombosis and Hemostasis (SETH) and Blood Transfusion (SETS) have developed a Consensus Document for the proper use of AABTs. A panel of experts convened by these 6 Societies have conducted a systematic review of the medical literature and have developed the 2013 Seville Consensus Document on Alternatives to Allogeneic Blood Transfusion, which only considers those AABT aimed at decreasing the transfusion of packed red cells. AABTs are defined as any pharmacological or non-pharmacological measure aimed at decreasing the transfusion of red blood cell concentrates, while preserving patient safety. For each AABT, the main question formulated, positively or negatively, is: "Does this particular AABT reduce the transfusion rate or not?" All the recommendations on the use of AABTs were formulated according to the Grades of Recommendation Assessment, Development and Evaluation (GRADE) methodology.

[Monitoring of tissue oxygen pressure (PtiO2) in cerebral hypoxia: diagnostic and therapeutic approach]. / Monitorización de la presión tisular de oxígeno (PtiO2) en la hipoxia cerebral: aproximación diagnóstica y terapéutica.

One of the main causes of secondary cerebral injury is cerebral hypoxia, basically of ischemic origin. However, cerebral tissue oxygenation depends on multiple physiological variables and cerebral hypoxia may be caused by an alteration of any one of them. Although several methods of continuous cerebral oxygenation monitoring of neurocritical patients have been developed, direct and continuous measurement of the oxygen pressure in the cerebral tissue (PtiO2) has been a reality in the handling of the neurocritical patients over recent years. This technique is highlighted by its reliability and value of the information that it provides. This present article presents a review of the most outstanding aspects of the PtiO2 monitoring and proposes a protocol for the interpretation of this monitoring technique. This algorithm attempts to facilitate the identification of the different types of different cerebral hypoxia and of the correct therapeutic choice in the complex decision making process in neurocritical patients at risk of cerebral hypoxia.

[Prevalence and treatment of anemia in critically ill patients]. / Prevalencia y tratamiento de la anemiaen el paciente crítico.

Anemia is a common condition among medical and surgical patients admitted to the intensive care unit (ICU) and generally has a multifactorial origin. In order to avoid the deleterious effects of anemia, 40% of ICU patients receive allogenic blood transfusion (ABT). This figure increases up to 70% if the ICU stay is longer than 7 days. However, ABT is associated with a dose-dependent increase in morbidity and mortality. In contrast, the administration of exogenous erythropoietin plus iron supplements, especially iv iron, improves anemia and reduces ABT requirements, although it does not reduce mortality. To ascertain whether treatment of anemia in the critically ill with exogenous erythropoietin and iron might improve outcomes and to optimize drug administration schedules and dosage, further studies with sufficient statistical power and adequate follow-up are warranted.

Melatonin biosynthesis in the thymus of humans and rats.

Melatonin is an indoleamine widely distributed in the evolution that shows a great functional versatility, playing an important role as a transmitter of photoperiodic information and exhibiting antioxidant, oncostatic, anti-aging and immunomodulatory properties. In vertebrates, this molecule is produced by the pineal gland and other extrapineal sites. The present study was carried out to investigate the presence of melatonin in thymus and the possibility of an endogenous melatonin synthesis in this organ, in which T cells are matured. In this work, we demonstrate in humans and rats that thymus contains melatonin, expresses the mRNAs encoding N-acetyltransferase and hydroxyindol-O-methyltransferase, the two key enzymes of the melatonin synthesis, and has this biosynthetic machinery activated. In addition, rat thymocytes cultured for 24 h exhibited high levels of melatonin. The results presented here suggest that human and rat thymuses are able to synthesize melatonin, which could have intracrine, autocrine and paracrine functions.

Nosocomial pneumonia in patients undergoing heart surgery.

OBJECTIVE: To determine the risk factors related to the presence of postsurgical nosocomial pneumonia (NP) in patients who had undergone cardiac surgery. DESIGN: A case-control study. SETTING: Postcardiac surgical intensive care unit at a university center. PATIENTS: A total of 45 patients with NP and 90 control patients collected during a 4-yr period. INTERVENTIONS: Pre-, intra-, and postoperative factors were collected and compared between two groups of patients (cases vs. controls) to determine their influence on the development of NP. The diagnosis of NP was always microbiologically confirmed as pulmonary specimen brush culture of > or =10(3) colony-forming units/mL or positive blood culture/pleural fluid culture by the growth of identical microorganisms isolated at the lung. For each patient diagnosed with NP, we selected control cases at a ratio of 1:2. MEASUREMENTS AND MAIN RESULTS: The incidence of NP was 6.5%. Multivariate analysis found a probable association of the following variables with a greater risk for the development of NP: reintubation (adjusted odds ratio [AOR], 62.5; 95% confidence interval [CI], 8.1-480; p = .01); nasogastric tube (AOR, 19.7; 95% CI, 3.5-109; p = .01), transfusion of > or =4 units of blood derivatives (AOR, 12.8; 95% CI, 2-82; p = .01) and empirical treatment with broad-spectrum antibiotics (AOR, 6.6; 95% CI, 1.2-36.8; p = .02). Culture results showed 13.3% of the NP to be of polymicrobial origin, whereas 77.3% of the microorganisms isolated were Gram-negative bacteria. The mortality (51 vs. 6.7%, p < .01) and the length of stay in the intensive care unit (25+/-14.8 days vs. 5+/-5 days, p < .01) were both greater in patients with NP. CONCLUSIONS: We conclude that the surgical risk factors, except the transfusion of blood derivatives, have little effect on the development of NP. Reintubation, nasogastric tubing, previous therapy with broad-spectrum antibiotics, and blood transfusion are factors most likely associated with NP acquisition.