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BACKGROUND: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority). CONCLUSIONS: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).
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Antifibrinolíticos , Ácido Tranexâmico , Antifibrinolíticos/efeitos adversos , Antifibrinolíticos/uso terapêutico , Canadá , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Procedimentos Cirúrgicos Operatórios , Trombose/induzido quimicamente , Trombose/tratamento farmacológico , Ácido Tranexâmico/efeitos adversos , Ácido Tranexâmico/uso terapêuticoRESUMO
BACKGROUND: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively. OBJECTIVE: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery. DESIGN: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723). SETTING: 110 hospitals in 22 countries. PATIENTS: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications. INTERVENTION: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery. MEASUREMENTS: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment. RESULTS: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term. LIMITATION: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels. CONCLUSION: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.
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Hipertensão , Hipotensão , Humanos , Anti-Hipertensivos/uso terapêutico , Complicações Pós-Operatórias/epidemiologia , Canadá , Hipotensão/etiologia , Hipotensão/prevenção & controle , Hipertensão/tratamento farmacológicoRESUMO
Background: Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the western world. Classic angina pectoris (AP) is a common reason to request prehospital emergency medical services (EMS). Nevertheless, data on diagnostic accuracy and common misdiagnoses are scarce. Therefore, the aim of this study is to evaluate the amount and variety of misdiagnoses and assess discriminating features. Methods: For this retrospective cohort study, all patients requiring EMS for suspected ACS in the city of Bonn (Germany) during 2018 were investigated. Prehospital and hospital medical records were reviewed regarding medical history, presenting signs and symptoms, as well as final diagnosis. Results: Out of 740 analyzed patients with prehospital suspected ACS, 283 (38.2%) were ultimately diagnosed with ACS (ACS group). Common diagnoses in the cohort with non-confirmed ACS (nACS group) consisted of unspecific pain syndromes, arrhythmias, hypertensive crises, and heart failure. ST segment elevation (adjusted odds-ratios [adj. OR] 2.70), male sex (adj. OR 1.71), T wave changes (adj. OR 1.27), angina pectoris (adj. OR 1.15) as well as syncope (adj. OR 0.63) were identified among others as informative predictors in a multivariable analysis using the lasso technique for data-driven variable selection. Conclusions: Misdiagnosed ACS is as common as 61.8% in this cohort and analyses point to a complex of conditions and symptoms (i.e., male sex, electrocardiographic (ECG) changes, AP) for correct ACS diagnosis while neurological symptoms were observed significantly more often in the nACS group (e.g., Glasgow Coma Scale (GCS) < 15, p = 0.03). To ensure adequate and timely therapy for a potentially critical disease as ACS a profound prehospital examination and patient history is indispensable.
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BACKGROUND: Patient Blood Management (PBM) is a patient-centred, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood whilst promoting patient safety and empowerment. The effectiveness and safety of PBM over a longer period have not yet been investigated. METHODS: We performed a prospectively designed, multicentre follow-up study with non-inferiority design. Data were retrospectively extracted case-based from electronic hospital information systems. All in-hospital patients (≥18 yr) undergoing surgery and discharged between January 1, 2010 and December 31, 2019 were included in the analysis. The PBM programme focused on three domains: preoperative optimisation of haemoglobin concentrations, blood-sparing techniques, and guideline adherence/standardisation of allogeneic blood product transfusions. The outcomes were utilisation of blood products, composite endpoint of in-hospital mortality and postoperative complications (myocardial infarction/ischaemic stroke/acute renal failure with renal replacement therapy/sepsis/pneumonia), anaemia rate at admission and discharge, and hospital length of stay. RESULTS: A total of 1 201 817 (pre-PBM: n=441 082 vs PBM: n=760 735) patients from 14 (five university/nine non-university) hospitals were analysed. Implementation of PBM resulted in a substantial reduction of red blood cell utilisation. The mean number of red blood cell units transfused per 1000 patients was 547 in the PBM cohort vs 635 in the pre-PBM cohort (relative reduction of 13.9%). The red blood cell transfusion rate was significantly lower (P<0.001) with odds ratio 0.86 (0.85-0.87). The composite endpoint was 5.8% in the PBM vs 5.6% in the pre-PBM cohort. The non-inferiority aim (safety of PBM) was achieved (P<0.001). CONCLUSIONS: Analysis of >1 million surgical patients showed that the non-inferiority condition (safety of Patient Blood Management) was fulfilled, and PBM was superior with respect to red blood cell transfusion. CLINICAL TRIAL REGISTRATION: NCT02147795.
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Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Transfusão de Sangue , Seguimentos , Estudos Retrospectivos , Adolescente , AdultoRESUMO
Background: Near-infrared spectroscopy (NIRS) is a commonly used technique to evaluate tissue oxygenation and prevent harmful cerebral desaturation in the perioperative setting. The aims of the present study were to assess whether surgery-related anemia can be detected via NIRS of cerebral oxygen saturation and to investigate the effects of different perioperative transfusion strategies on cerebral oxygenation, potentially affecting transfusion decision-making. Study Design and Methods: Data from the ongoing multicenter LIBERAL-Trial (liberal transfusion strategy to prevent mortality and anemia-associated ischemic events in elderly noncardiac surgical patients, LIBERAL) were used. In this single-center sub-study, regional cerebral oxygenation saturation (rSO2) was evaluated by NIRS at baseline, pre-, and post-RBC transfusion. The obtained values were correlated with blood gas analysis-measured Hb concentrations. Results: rSO2 correlated with Hb decline during surgery (r = 0.35, p < 0.0001). Different RBC transfusion strategies impacted rSO2 such that higher Hb values resulted in higher rSO2. Cerebral desaturation occurred at lower Hb values more often. Discussion: Cerebral oxygenation monitoring using NIRS provides noninvasive rapid and continuous information regarding perioperative alterations in Hb concentration without the utilization of patients' blood for blood sampling. Further investigations are required to demonstrate if cerebral rSO2 may be included in future individualized transfusion decision strategies.
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Influence of digital documentation on working hours and workflow in the intensive care unit: An observational pre-post-study Abstract: Background: The introduction of digital patient documentation systems in hospitals and intensive care units is increasing in Germany. The effects of these systems on the workflow of nurses have hardly been studied. Aim: It is analysed how high the workload is with a digital documentation system compared to paper-based documentation, how the workflow changes and how the digital documentation is evaluated in comparison to paper-based in terms of usability, time required and documentation quality. Methods: Before (to) and after the introduction of the digital patient documentation system (t1), the time for documentation and the documentation frequency was measured in a prospective pre-post observation study using an app configured specifically for this purpose, and both survey periods were statistically compared (Mann-Whitney-U-test). Furthermore, a survey of nursing staff on digital patient documentation was carried out. Results: The working time for the documentation remains the same after digitization. However, 80% of respondents state that the documentation time would have been reduced. Furthermore, the number of documentation processes decreases significantly (p = 0.03). In addition, a majority (55%) indicated an increase in documentation quality. Conclusions: Digital patient documentation does not necessarily save working time, but it defragments the process of documentation work and has the potential to positively influence the documentation workflow.
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BACKGROUND/PURPOSE: Discharge decisions in Intensive Care Unit (ICU) patients are frequently taken under pressure to free up ICU beds. In the absence of established guidelines, the evaluation of discharge readiness commonly underlies subjective judgements. The challenge is to come to the right decision at the right time for the right patient. A premature care transition puts patients at risk of readmission to the ICU. Delayed discharge is a waste of resources and may result in over-treatment and suboptimal patient flow. More objective decision support is required to assess the individual patient's discharge readiness but also the current care capabilities of the receiving unit. METHODS: In a modified online Delphi process, an international panel of 27 intensive care experts reached consensus on a set of 28 intensive care discharge criteria. An initial evidence-based proposal was developed further through the panelists' edits, adding, comments and voting over a course of 5 rounds. Consensus was defined as achieved when ≥ 90% of the experts voted for a given option on the Likert scale or in a multiple-choice survey. Round 1 to 3 focused on inclusion and exclusion of the criteria based on the consensus threshold, where round 3 was a reiteration to establish stability. Round 4 and 5 focused on the exact phrasing, values, decision makers and evaluation time frames per criterion. RESULTS: Consensus was reached on a standard set of 28 ICU discharge criteria for adult ICU patients, that reflect the patient's organ systems ((respiratory (7), cardiovascular (9), central nervous (1), and urogenital system (2)), pain (1), fluid loss and drainages (1), medication and nutrition (1), patient diagnosis, prognosis and preferences (2) and institution-specific criteria (4). All criteria have been specified in a binary decision metric (fit for ICU discharge vs. needs further intensive therapy/monitoring), with consented value calculation methods where applicable and a criterion importance rank with "mandatory to be met" flags and applicable exceptions. CONCLUSION: For a timely identification of stable intensive care patients and safe and efficient care transitions, a standardized discharge readiness evaluation should be based on patient factors as well as organizational boundary conditions and involve multiple stakeholders.
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Alta do Paciente , Quartos de Pacientes , Adulto , Consenso , Técnica Delphi , Humanos , Unidades de Terapia IntensivaRESUMO
BACKGROUND: The validity of current tools for intraoperative objective assessment of nociception/antinociception balance during anesthesia in young and very young surgery children is unknown. AIM: Primary aim of the study was to test the hypothesis that the Newborn Infant Parasympathetic Evaluation (NIPE) index performs better in indicating nociception in anesthetized children below 2 years than changes in heart rate. Secondary aims were to evaluate associations between intraoperative changes in NIPE index values and postoperative pain and emergence delirium. METHODS: Fifty-one children aged <2 years who underwent surgery were included in this prospective observational study. Patients were assigned to either group 1 (healthy children, n = 31) or group 2 (critically ill, ventilated premature infants and neonates, n = 20). The NIPE index and heart rate in response to three defined nociceptive stimuli were continuously recorded. Two different scales, Kindliche Unbehagens- und Schmerzskala (KUS) and Pediatric Anesthesia Emergence Delirium (PAED) as well as a Pain Questionnaire were used to assess postoperative pain levels and emergence delirium. RESULTS: In total, 110 nociceptive events were evaluated. The analysis revealed a statistically significant association between a decrease in the NIPE index and all nociceptive stimuli, with a sensitivity of 92% and a specificity of 96%. The mean percentage decrease ranged from approx. 15%-30% and was highly statistically significant in both groups and for each of the nociceptive events except for venous puncture (p = .004). In contrast, no consistent change in heart rate was demonstrated. The KUS and PAED scale scores were significantly associated with the duration of anesthesia (p = .04), but not with intraoperative NIPE depression. CONCLUSION: The NIPE index was reliable for assessing intraoperative nociception in children aged <2 years and was more reproducible for detecting specific nociceptive stimuli during general anesthesia than heart rate. An effect on postoperative outcome is still elusive.
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Delírio do Despertar , Nociceptividade , Anestesia Geral , Criança , Estado Terminal , Delírio do Despertar/diagnóstico , Frequência Cardíaca/fisiologia , Humanos , Lactente , Recém-Nascido , Medição da Dor , Dor Pós-OperatóriaRESUMO
PURPOSE: Anaemia is common in patients presenting with aneurysmal subarachnoid (aSAH) and intracerebral haemorrhage (ICH). In surgical patients, anaemia was identified as an idenpendent risk factor for postoperative mortality, prolonged hospital length of stay (LOS) and increased risk of red blood cell (RBC) transfusion. This multicentre cohort observation study describes the incidence and effects of preoperative anaemia in this critical patient collective for a 10-year period. METHODS: This multicentre observational study included adult in-hospital surgical patients diagnosed with aSAH or ICH of 21 German hospitals (discharged from 1 January 2010 to 30 September 2020). Descriptive, univariate and multivariate analyses were performed to investigate the incidence and association of preoperative anaemia with RBC transfusion, in-hospital mortality and postoperative complications in patients with aSAH and ICH. RESULTS: A total of n = 9081 patients were analysed (aSAH n = 5008; ICH n = 4073). Preoperative anaemia was present at 28.3% in aSAH and 40.9% in ICH. RBC transfusion rates were 29.9% in aSAH and 29.3% in ICH. Multivariate analysis revealed that preoperative anaemia is associated with a higher risk for RBC transfusion (OR = 3.25 in aSAH, OR = 4.16 in ICH, p < 0.001), for in-hospital mortality (OR = 1.48 in aSAH, OR = 1.53 in ICH, p < 0.001) and for several postoperative complications. CONCLUSIONS: Preoperative anaemia is associated with increased RBC transfusion rates, in-hospital mortality and postoperative complications in patients with aSAH and ICH. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02147795, https://clinicaltrials.gov/ct2/show/NCT02147795.
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Anemia , Hemorragia Subaracnóidea , Adulto , Anemia/complicações , Anemia/epidemiologia , Anemia/terapia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/terapia , Transfusão de Eritrócitos/efeitos adversos , Humanos , Sistema de Registros , Estreptotricinas , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/terapiaRESUMO
PURPOSE: Postoperative delirium (POD) is an often unrecognized adverse event in older people after surgery. The aim of this subgroup analysis of the PRe-Operative Prediction of postoperative DElirium by appropriate SCreening (PROPDESC) trial in patients aged 70 years and older was to identify preoperative risk factors and the impact of POD on length of stay (LOS) in intensive care unit (ICU) and hospital. METHODS: Of the total 1097 patients recruited at a German university hospital (from September 2018 to October 2019) in the PROPDESC prospective observational study, 588 patients aged 70 years and older (mean age 77.2 ± 4.7 years) were included for subgroup analysis. The primary endpoint POD was considered positive if one of the following tests were positive on any of the five postoperative visit days: Confusion Assessment Method for ICU (CAM-ICU), Confusion Assessment Method (CAM), 4'A's (4AT) and Delirium Observation Scale (DOS). Trained doctoral students carried out these visitations and additionally the nursing staff were interviewed for completion of the DOS. To evaluate the independent effect of POD on LOS in ICU and in hospital, a multi-variable linear regression analysis was performed. RESULTS: The POD incidence was 25.9%. The results of our model showed POD as an independent predictor for a prolonged LOS in ICU (36%; 95% CI 4-78%; < 0.001) and in hospital (22%; 95% CI 4-43%; < 0.001). CONCLUSION: POD has an independent impact on LOS in ICU and in hospital. Based on the effect of POD for the elderly, a standardized risk screening is required. TRAIL REGISTRATION: German Registry for Clinical Studies: DRKS00015715.
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Delírio , Complicações Pós-Operatórias , Idoso , Idoso de 80 Anos ou mais , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Hospitais Universitários , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/terapia , Fatores de RiscoRESUMO
BACKGROUND: Postoperative delirium (POD) is a relevant and underdiagnosed complication after cardiac surgery that is associated with increased intensive care unit (ICU) and hospital length of stay (LOS). The aim of this subgroup study was to compare the frequency of tested POD versus the coded International Statistical Classification of Diseases and Related Health Problems (ICD) diagnosis of POD and to evaluate the influence of POD on LOS in ICU and hospital. METHODS: 254 elective cardiac surgery patients (mean age, 70.5 ± 6.4 years) at the University Hospital Bonn between September 2018 and October 2019 were evaluated. The endpoint tested POD was considered positive, if one of the tests Confusion Assessment Method for ICU (CAM-ICU) or Confusion Assessment Method (CAM), 4 'A's Test (4AT) or Delirium Observation Scale (DOS) was positive on one day. RESULTS: POD occurred in 127 patients (50.0%). LOS in ICU and hospital were significantly different based on presence (ICU 165.0 ± 362.7 h; Hospital 26.5 ± 26.1 days) or absence (ICU 64.5 ± 79.4 h; Hospital 14.6 ± 6.7 days) of POD (p < 0.001). The multiple linear regression showed POD as an independent predictor for a prolonged LOS in ICU (48%; 95%CI 31-67%) and in hospital (64%; 95%CI 27-110%) (p < 0.001). The frequency of POD in the study participants that was coded with the ICD F05.0 and F05.8 by hospital staff was considerably lower than tests revealed by the study personnel. CONCLUSION: Approximately 50% of elderly patients who underwent cardiac surgery developed POD, which is associated with an increased ICU and hospital LOS. Furthermore, POD is highly underdiagnosed in clinical routine.
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Procedimentos Cirúrgicos Cardíacos , Delírio , Idoso , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Hospitais Universitários , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Opioid-related adverse events are a serious problem in hospitalized patients. Little is known about patients who are likely to experience opioid-induced respiratory depression events on the general care floor and may benefit from improved monitoring and early intervention. The trial objective was to derive and validate a risk prediction tool for respiratory depression in patients receiving opioids, as detected by continuous pulse oximetry and capnography monitoring. METHODS: PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) was a prospective, observational trial of blinded continuous capnography and oximetry conducted at 16 sites in the United States, Europe, and Asia. Vital signs were intermittently monitored per standard of care. A total of 1335 patients receiving parenteral opioids and continuously monitored on the general care floor were included in the analysis. A respiratory depression episode was defined as respiratory rate ≤5 breaths/min (bpm), oxygen saturation ≤85%, or end-tidal carbon dioxide ≤15 or ≥60 mm Hg for ≥3 minutes; apnea episode lasting >30 seconds; or any respiratory opioid-related adverse event. A risk prediction tool was derived using a multivariable logistic regression model of 46 a priori defined risk factors with stepwise selection and was internally validated by bootstrapping. RESULTS: One or more respiratory depression episodes were detected in 614 (46%) of 1335 general care floor patients (43% male; mean age, 58 ± 14 years) continuously monitored for a median of 24 hours (interquartile range [IQR], 17-26). A multivariable respiratory depression prediction model with area under the curve of 0.740 was developed using 5 independent variables: age ≥60 (in decades), sex, opioid naivety, sleep disorders, and chronic heart failure. The PRODIGY risk prediction tool showed significant separation between patients with and without respiratory depression (P < .001) and an odds ratio of 6.07 (95% confidence interval [CI], 4.44-8.30; P < .001) between the high- and low-risk groups. Compared to patients without respiratory depression episodes, mean hospital length of stay was 3 days longer in patients with ≥1 respiratory depression episode (10.5 ± 10.8 vs 7.7 ± 7.8 days; P < .0001) identified using continuous oximetry and capnography monitoring. CONCLUSIONS: A PRODIGY risk prediction model, derived from continuous oximetry and capnography, accurately predicts respiratory depression episodes in patients receiving opioids on the general care floor. Implementation of the PRODIGY score to determine the need for continuous monitoring may be a first step to reduce the incidence and consequences of respiratory compromise in patients receiving opioids on the general care floor.
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Analgésicos Opioides/efeitos adversos , Capnografia/métodos , Oximetria/métodos , Insuficiência Respiratória/induzido quimicamente , Insuficiência Respiratória/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Monitorização Fisiológica , Valor Preditivo dos Testes , Estudos Prospectivos , Taxa Respiratória , Fatores de RiscoRESUMO
BACKGROUND: The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. METHODS: We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery. RESULTS: A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10- 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10- 5 from the GWAS. CONCLUSIONS: We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.
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Injúria Renal Aguda/genética , Fibrilação Atrial/genética , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Delírio/genética , Infarto do Miocárdio/genética , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Injúria Renal Aguda/diagnóstico , Idoso , Fibrilação Atrial/diagnóstico , Proteínas do Citoesqueleto/genética , Delírio/diagnóstico , Fosfatases de Especificidade Dupla/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Proteínas de Choque Térmico HSC70/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Estudos Multicêntricos como Assunto , Infarto do Miocárdio/diagnóstico , Fosfoproteínas Fosfatases/genética , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Acidente Vascular Cerebral/diagnóstico , Resultado do TratamentoRESUMO
BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains. METHODS: We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90. RESULTS: A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed. CONCLUSIONS: Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.).
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Procedimentos Cirúrgicos Cardíacos , Precondicionamento Isquêmico/métodos , Complicações Pós-Operatórias/prevenção & controle , Idoso , Anestesia Intravenosa , Ponte Cardiopulmonar , Método Duplo-Cego , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Isquemia , Estimativa de Kaplan-Meier , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Propofol , Estudos Prospectivos , Falha de Tratamento , Troponina/sangue , Extremidade Superior/irrigação sanguíneaRESUMO
BACKGROUND: Preoperative anemia and allogeneic blood transfusions (ABTs) may affect outcomes in cancer surgery. The prevalence of anemia, the use of ABTs, the risks of transfusions, lengths of stay and mortality of oncological patients undergoing radical cystectomy were investigated in three University Hospitals in Germany. PATIENTS AND METHODS: Hospital records of 220 consecutive patients undergoing radical cystectomy from 2010 to 2012 were retrospectively analyzed for independent risk factors of ABT and unfavorable outcomes (readmission, increased length of stay (LOS) or death) using multivariate regression analysis. RESULTS: Preoperative anemia was present in 40%. 70% of patients received blood transfusions. Low preoperative and intraoperative nadir hemoglobin levels were associated with receipt of ABT (OR 1.33, P = 0.04 and OR 2.94, P < 0.001 respectively). Transfusion of ten or more red blood cell units (RBCs) during the entire hospital stay was a predictor of an increased LOS (P < 0.001) and death (OR 52, 95%CI [5.9, 461.3], P < 0.001), compared to non-transfused patients. Preoperative ABT and ASA scores were associated with ≥10RBCs. CONCLUSION: Anemic patients undergoing radical cystectomy had a high risk to receive ABTs. Preoperative transfusions and transfusion of ≥10RBCs during the entire hospital stay may increase patient`s mortality. Prospective, randomized controlled studies have to follow this study.
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Anemia/terapia , Transfusão de Sangue , Cistectomia , Mortalidade Hospitalar , Hospitalização , Cuidados Pré-Operatórios , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Anemia/epidemiologia , Eritrócitos/metabolismo , Feminino , Hemoglobinas/metabolismo , Humanos , Tempo de Internação , Masculino , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: Cardiopulmonary bypass (CPB) surgery commonly threatens the heart and remote organs with ischemia-reperfusion injury. Transient episodes of ischemia to nonvital tissue, known as remote ischemic preconditioning (RIPC), is thought to help local and remote vital organs to withstand subsequent ischemic insults. DESIGN: Prospective, randomized, double-blinded control trial. SETTING: Tertiary referral academic teaching hospital. PARTICIPANTS: Thirty patients undergoing elective CPB surgery INTERVENTION: RIPC was achieved via three 5-minute cycles of upper limb ischemia using a blood pressure cuff or control (sham cuff). MEASUREMENTS AND MAIN RESULTS: Primary outcome was the occurrence of intestinal injury, as measured by an increase in intestinal fatty acid binding protein (I-FABP). Secondary outcomes included incidence of gastrointestinal complications and duration of intensive care unit (ICU) stay. RIPC did not affect serum IFABP levels at the end of surgery and on the first postoperative day (p = 0.697 and p = 0.461, respectively). For all patients, mean I-FABP levels significantly increased at the end of surgery and decreased to under baseline levels on the first postoperative day (from a mean [± standard deviation] baseline value of 764 ± 492 pg/mL to 2,002 ± 974 pg/mL and decreased to 568 ± 319 pg/mL, p < 0.001). All patients remained clinically absent of gastrointestinal complications until hospital discharge. Duration of ICU stay was not correlated with I-FABP levels at the end of surgery. Neither duration of CPB nor duration of aortic clamping significantly correlated with postoperative I-FABP levels. CONCLUSIONS: These findings suggest that RIPC does not affect intestinal injury in patients undergoing CPB surgery. In patients undergoing cardiac surgery, intestinal injury appears to be moderate and transient without any clinical relevant complication.
Assuntos
Ponte de Artéria Coronária/efeitos adversos , Intestinos/irrigação sanguínea , Precondicionamento Isquêmico , Traumatismo por Reperfusão/prevenção & controle , Idoso , Ponte Cardiopulmonar , Método Duplo-Cego , Proteínas de Ligação a Ácido Graxo/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos ProspectivosRESUMO
Trifolium polymorphum Poir. is an amphicarpic forage legume from southern Brazil, Uruguay, Argentina, Paraguay and Chile. Information on the genetic diversity of natural populations in natural grasslands in southern Brazil is limited. In order to increase the knowledge about this species, an analysis of the genetic diversity was carried out in 10 natural populations of T. polymorphum with the use of 20 microsatellite markers. The expected heterozygosity in T. polymorphum populations ranged from 0.40 to 0.43, with a mean of 0.42. A total of 193 alleles were detected with a mean of 9.3 alleles per locus and polymorphic information content (PIC) for these markers of 0.62 to 0.89 with a mean of 0.84.The grouping based on the Jaccard's coefficient of similarity classified populations, regardless of their regions of origin, into two groups with a mean similarity coefficient of 0.32, reflecting the high genetic variability of the populations, especially those located in the Campanha phytogeographic region. This information on diversity can be used to plan future germplasm collection strategies for conservation purposes and also for the breeding of the species.
Assuntos
DNA de Plantas , Variação Genética , Repetições de Microssatélites/genética , Trifolium/genética , Alelos , Brasil , DNA de Plantas/análise , Triagem de Portadores Genéticos , Polimorfismo Genético , Especificidade da EspécieRESUMO
Pt is a common redox electrode used to follow oscillations qualitatively in the Briggs-Rauscher (BR) and the Bray-Liebhafsky (BL) reactions from the time of their discovery. Although the potential oscillations of the electrode reflect the temporal pattern of the reaction properly, there is no general agreement as to how that potential is determined by the components of the reaction mixture. In this article, first we investigate how iodine species in different oxidation states affect the potential of a Pt electrode. It was found that I(+3) and I(+5) species do not affect the potential; only I-, I2, and HOI may have an influence. Although the latter three species are always present simultaneously as participants of the rapid iodine hydrolysis equilibrium, it was found that below and above the so-called hydrolysis limit potential (HLP, where the iodide and HOI concentrations are equal) the actual potential determining redox couple is different. Below the HLP, it is the traditional I2/I- redox couple, but above the HLP, it is the HOI/I2 redox pair that determines the potential of a Pt electrode. That change in the potential control mechanism was proven experimentally by exchange current measurements. In addition, from the potential response of the Pt electrode below and above the HLP, it was possible to calculate the equilibrium constant of the iodine hydrolysis as K°H = (4.97 ± 0.20) × 10-13 M2, in rather good agreement with earlier measurements. We also studied the perturbing effect of H2O2 on the previously mentioned potentials. The concentration of H2O2 was 0.66 M, as in the BR reaction studied here. It was found that below the HLP, the perturbing effect of H2O2 was minimal but above the HLP, H2O2 shifted the mixed potential considerably down toward the HLP. In our experiments with the BR reaction, the potential oscillations of the Pt electrode crossed the HLP, indicating that from time to time the HOI concentration exceeds that of the iodide. We can conclude that although the perturbing effect of H2O2 prevents the calculation of concentrations from Pt potentials above the HLP, [I-]/[I2]1/2 ratios can be calculated as a good approximation from Pt potentials below the HLP.
RESUMO
The Paspalum genus includes several species that are important for livestock in Rio Grande do Sul, such as P. notatum and P. guenoarum, typical of native pastures of the Pampa biome. The aim of this study was to investigate forage production and chemical composition of four ecotypes of these species in relation to the cv. 'Pensacola' (P. notatum). Ecotypes of P. guenoarum (Azulão and Baio) and P. notatum (André da Rocha and Bagual) and the cv. 'Pensacola' were evaluated for two years, during which four cuts/year were made. The work was carried out under field conditions at the Agronomic Experimental Station of the Federal University of Rio Grande do Sul (30°05'S; 51°39'W), in a completely randomized design. P. guenoarum stood out for higher productivity and greater tolerance to cold; the Azulão ecotype showed more autumn production in relation to the other ecotypes. Crude protein content ranged from 14 (Baio) to 15% ('Pensacola'); for neutral detergent fiber, the variation was 68 (Azulão) to 71% ('Pensacola') and for acid detergent fiber there was a variation of 38 ('Pensacola') to 43% (Baio). The data demonstrates the potential of native genotypes for use as cattle feeding in southern Brazil.
Assuntos
Ração Animal/análise , Paspalum/classificação , Animais , Brasil , Bovinos , Estações do AnoRESUMO
OBJECTIVE: To determine whether the implementation of patient blood management (PBM) is effective to decrease the use of red blood cell without impairment of patient's safety. BACKGROUND: The World Health Organization encouraged all member states to implement PBM programs employing multiple combined strategies to increase and preserve autologous erythrocyte volume to minimize red blood cell transfusions. Data regarding safety issues are not sufficiently available. METHODS: In this prospective, multicenter study, surgical inpatients from four German University Hospitals were analyzed before (pre-PBM) and after the implementation of PBM. PBM program included multiple measures (ie, preoperative optimization of hemoglobin levels, blood-sparing techniques, and standardization of transfusion practice). Primary aim was to show noninferiority of the PBM cohort with a margin of 0.5%. Secondary endpoints included red blood cell utilization. RESULTS: A total of 129,719 patients discharged between July 2012 and June 2015 with different inclusion periods for pre-PBM (54,513 patients) and PBM (75,206 patients) were analyzed. The primary endpoint was 6.53% in the pre-PBM versus 6.34% in the PBM cohort. The noninferiority aim was achieved (P < 0.001). Incidence of acute renal failure decreased in the PBM cohort (2.39% vs 1.67%; P < 0.001, regression model). The mean number of red blood cell transfused per patient was reduced from 1.21â±â0.05 to 1.00â±â0.05 (relative change by 17%, P < 0.001). CONCLUSIONS: The data presented show that implementation of PBM with a more conscious handling of transfusion practice can be achieved even in large hospitals without impairment of patient's safety. Further studies should elucidate which PBM measures are most clinically and cost effective. TRIAL REGISTRATION: PBM-Study ClinicalTrials.gov, NCT01820949.