Transfusion Requirements After Cardiac Surgery The TRACS Randomized Controlled Trial

Context Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. Objective To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery. Design, Setting, and Patients The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n=502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat. Intervention Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit >= 30%) or to a restrictive strategy (hematocrit >= 24%). Main Outcome Measure Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at -8% (ie, 8% minimal clinically important increase in occurrence of the composite end point). Results Hemoglobin concentrations were maintained at a mean of 10.5 g/dL(95% confidence interval [CI], 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.09.2) in the restrictive-strategy group (P<.001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P<.001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% [95% CI, -6% to 4%]; P=.85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 [95% CI, 1.1-1.4]; P=.002). Conclusion Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity. Trial Registration clinicaltrials.gov Identifier: NCT01021631 JAMA. 2010; 304(14):1559-1567 www.jama.com

Penetration of cefuroxime in subcutaneous tissue during coronary artery bypass grafting surgery

A sensitive and rapid HPLC assay for determining cefuroxime penetration in the subcutaneous tissue near to surgical incision of patients submitted to coronary artery bypass grafting (CABC) with or without cardiopulmonary bypass (CPB) was performed. Blood and subcutaneous tissue samples were collected from 14 patients. in four periods during surgery. The analytical method presented linearity from 0.5 to 100 mu g/g. LOQ = 0.50 mu g/g, LOD = 0.25 mu g/g. intra- and interday precision (%CV) ranged from 4.9 to 8.9% and 6.4 to 9.9%, respectively, and intra-and interday accuracy expressed as % of the nominal concentration ranged from 87.1 to 104.6% and 94.8 to 103.8%, respectively (mean of three concentrations). Relative recovery was 98.4%. Tissue/plasma ratios obtained for CPB and non-CPB were, respectively: 14.6% vs 19.0% (0.6 h); 15.7% vs 15.7% (2.1 h); 22.5% vs 19.9% (3.6 h); 15.7% vs 18.8% (4.5 h). Data obtained indicate that tissue/plasma ratio remains unchanged in CPB and non-CPB patients during all period of surgery and the CPB does not affect the penetration of cefuroxime in tissues close to the surgical wound. (C) 2009 Elsevier B.V. All rights reserved.

Electrical burns: A retrospective analysis across a 5-year period

This study aims to review the experience, at an institution, with patients who suffered electrical burns and study the peculiar characteristics of this type of burn as well as its complications and epidemiological aspects. The study includes medical records of patients with electrical burns who were admitted to the Burn Unit of Hospital das Clinicas in Sao Paulo, Brazil, from November 2001 to October 2006. They were classified into four categories: high voltage (>= 1000 V), low voltage (<1000 V), `flash burn` (in which there is no electrical current flow through the body of the patient) and burns caused by lightning. The complications were more severe and common in the high-voltage group, while longer hospital stays and more complex surgical procedures due to the greater depth of burns were also observed in this group. High-voltage burns are mainly labour-/occupation-related. The majority of the patients were young men at the beginning of their professional lives. This factor generates an important socio-economic impact due to the high incidence of sequelae, resulting in amputations, rendering them unable to maintain their occupations. (C) 2009 Elsevier Ltd and ISBI. All rights reserved.

Inflammatory Cytokines during Liver Transplantation: Prospective Randomized Trial Comparing Conventional and Piggyback Techniques

Background/Aims: Cytokines have a significant role in the response to injury following liver transplantation, but the origin and course of such molecules are not completely known. The aim of this study was to evaluate the production and liver metabolism of the inflammatory cytokines interleukin (IL)-1 beta, IL-6, IL-8, interferon (IFN)-Y and tumor necrosis factor (TNF)-alpha in orthotopic liver transplantation (OLT), comparing the conventional and the piggyback methods. Methodology: We performed a study of 30 patients who underwent elective OLT and were randomized for the conventional or piggyback techniques at the beginning of the operation. The amount of cytokines and their hepatic metabolism were calculated based on plasma concentrations and vascular blood flow at 2, 5, 10, 15, 30, 60, 90, and 120 minutes after revascularization. Results: The amount of IL-1 beta in portal blood was higher in patients who underwent surgery using the conventional technique (estimate interest = 63,783.9 +/- 16,586.1 pg/min, versus 11,979.6 +/- 16,585.7 pg/min in the piggyback group, p=0.035). There were no significant differences between the two operative`s methods for IL-6, IL-8, IFN-Y and TNF-alpha production. The hepatic metabolism of cytokines was not different between groups. Although all the curves showed higher amounts of cytokines with the conventional technique, these were not statistically significant. Conclusion: The study shows the similarity between the two techniques concerning the stimuli for the production of inflammatory molecules.

Low Hematocrit Levels Increase Intracranial Pressure in an Animal Model of Cryogenic Brain Injury

Background: Brain injury is responsible for significant morbidity and mortality in trauma patients, but controversy still exists over optimal fluid management for these patients. This study aimed to investigate the effects of acute hemodilution with hydroxyethyl starch (HES) or lactated Ringer`s solution (LR) in intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in dogs submitted to a cryogenic brain injury model. Methods: Design-Prospective laboratory animal study. Setting-Research laboratory in a teaching hospital. Subjects-Thirty-five male mongrel dogs. Interventions-Animals were enrolled to five groups: control, hemodilution with LR or HES 6% to an hematocrit target of 27% or 35%. Results: ICP and CPP levels were measured after cryogenic brain injury. Hemodilution promotes an increment of ICP levels, which decreases CPP when hematocrit target was estimated in 27.% after hemodilution. However, no differences were observed regarding crystalloid or colloid solution used for hemodilution in ICP and CPP levels. Conclusions: Hemodilution to a low hematocrit level increases ICP and decreases CPP scores in dogs submitted to a cryogenic brain injury. These results suggest that excessive hemodilution to a hematocrit below 30% should be avoided in traumatic brain injury patients.

Estradiol`s Salutary Effects on Keratinocytes Following Trauma-Hemorrhage Are Mediated by Estrogen Receptor (ER)-alpha and ER-beta

Although administration of 17 beta-estradiol (estrogen) following trauma-hemorrhage attenuates the elevation of cytokine production and mitogen-activated protein kinase (MAPK) activation in epidermal keratinocytes, whether the salutary effects of estrogen are mediated by estrogen receptor (ER)-alpha. or ER-beta is not known. To determine which estrogen receptor is the mediator, we subjected C3H/HeN male mice to trauma-hemorrhage (2-cm midline laparotomy and bleeding of the animals to a mean blood pressure of 35 mmHg and maintaining that pressure for 90 min) followed by resuscitation with Ringer`s lactate (four times the shed blood volume) At the middle of resuscitation we subcutaneously injected ER-alpha agonist propyl pyrazole trial (PPT; 5 mu g/kg), ER-beta agonist diarylpropionitrile (DPN; 5 mu g/kg), estrogen (50 mu g/kg), or ER antagonist ICI 182,780 (150 mu g/kg). Two hours after resuscitation, we isolated keratinocytes, stimulated them with lipopolysaccharide for 24 In (5 mu g/mL for maximum cytokine production), and measured the production of interleukin (IL)-6, IL-10, IL-12, and INF-alpha and the activation of MAPK. Keratinocyte cytokine production markedly increased and MAPK activation occurred following trauma-hemorrhage but were normalized by administration of estrogen, PPT and DPN. PPT and DPN administration were equally effective in normalizing the inflammatory response of keratinocytes, indicating that both ER-alpha. and ER-beta mediate the salutary effects of estrogen on kerotinocytes after trauma-hemorrhage.

Adult-onset Still`s Disease with Pulmonary and Cardiac Involvement and Response to Intravenous Immunoglobulin

Cardiopulmonary manifestations of adult-onset Still`s disease (AOSD) include pericarditis, pleural effusion, transient pulmonary infiltrates, pulmonary interstitial disease and myocarditis. Serositis are common but pneumonitis and myocarditis are not and bring elevated risk of mortality. They may manifest on disease onset or flares. Previously reported cases were treated with high-dose glucocorticoids and immunosupressants and, when refractory, intravenous immunoglobulin (IVIG). We report an AOSD patient whose flare presented with severe pleupneumonitis and myopericarditis and, following nonresponse to a methylprednisolone pulse, high dose of prednisone and cyclosporine A, recovered after a 2-day 1g/kg/day IVIG infusion.

Acute Pancreatitis Hypertonic Saline Increases Heat Shock Proteins 70 and 90 and Reduces Neutrophil Infiltration in Lung Injury

Objectives: Acute pancreatitis (AP) protease release induces lung parenchymal destruction via matrix metalloproteinases (MMPs), a neutrophil (polymorphonuclear leukocyte)-dependent process. Recent studies in hemorrhagic shock revealed that hypertonic saline (HTS) has an anti-inflammatory effect and can inhibit a variety of neutrophil functions. The aim of this study was to determine whether HTS and its actions in the pathway of neutrophil migration, MMPs, and heat shock proteins (HSPs) are effective in protecting the lung from injury associated with AP. Methods: We determined neutrophil infiltration and expressions of MMPs and HSPs in the lung tissue after AP induced by retrograde infusion of 2.5% of sodium taurocholate. Results: Animals submitted to AP that received HTS compared with those who received normal saline presented with increased HSP70 and HSP90 expressions and reduced myeloperoxidase levels and MMP-9 expression and activity. Conclusions: Our data raised the hypothesis that a sequence of HTS lung protection events increases HSP70 and HSP90, inhibiting infiltration of neutrophils and their protease actions in the lung.

Hypertonic saline reduces metalloproteinase expression in liver during pancreatitis

P>We recently demonstrated that hypertonic saline reduces inflammation and mortality in acute pancreatitis. The present study investigated the effects of hypertonic saline in metalloproteinase (MMP) regulation and pancreatitis-associated hepatic injury. Wistar rats were divided into four groups: (i) control, not subjected to insult or treatment; (ii) no treatment (NT), induction of pancreatitis (retrograde infusion of 2.5% sodium taurocholate (1.0 mL/kg)), but no further treatment; (iii) normal saline (NS), induction of pancreatitis and treatment with normal saline (0.9% NaCl, 34 mL/kg, i.v. bolus, 1 h after the induction of pancreatitis); and (iv) hypertonic saline (HS), induction of pancreatitis and treatment with hypertonic saline (7.5% NaCl, 4 mL/kg administered over a period of 5 min, 1 h after the induction of pancreatitis). In all four groups, 4, 12 and 24 h after the induction of pancreatitis, liver tissue samples were assayed to determine levels of MMP-2, MMP-9, 47 kDa heat shock protein (HSP47) and collagen (Type I and III). Compared with the control group, MMP-9 expression and activity was increased twofold in the NS and NT groups 4 and 12 h after the induction of pancreatitis, but remained at basal levels in the HS group. In contrast, MMP-2 expression was increased twofold 12 h after the induction of pancreatitis only in the NS group, whereas the expression of HSP47 was increased 4 h after the induction of pancreatitis in the NS and NT groups. Greater extracellular matrix remodelling occurred in the NS and NT groups compared with the HS group, probably as a result of the hepatic wound-healing response to repeated injury. However, the collagen content in hepatic tissue remained at basal levels in the HS group. In conclusion, the results of the present study indicate that hypertonic saline is hepatoprotective and reduces hepatic remodelling, maintaining the integrity of the hepatic extracellular matrix during pancreatitis. Hypertonic saline-mediated regulation of MMP expression may have clinical relevance in pancreatitis-associated liver injury.

Five-Year Follow-Up of a Randomized Comparison Between Off-Pump and On-Pump Stable Multivessel Coronary Artery Bypass Grafting. The MASS III Trial

Background-Coronary artery bypass graft surgery with cardiopulmonary bypass is a safe, routine procedure. Nevertheless, significant morbidity remains, mostly because of the body`s response to the nonphysiological nature of cardiopulmonary bypass. Few data are available on the effects of off-pump coronary artery bypass graft surgery (OPCAB) on cardiac events and long-term clinical outcomes. Methods and Results-In a single-center randomized trial, 308 patients undergoing coronary artery bypass graft surgery were randomly assigned: 155 to OPCAB and 153 to on-pump CAB (ONCAB). Primary composite end points were death, myocardial infarction, further revascularization (surgery or angioplasty), or stroke. After 5-year follow-up, the primary composite end point was not different between groups (hazard ratio 0.71, 95% CI 0.41 to 1.22; P=0.21). A statistical difference was found between OPCAB and ONCAB groups in the duration of surgery (240 +/- 65 versus 300 +/- 87.5 minutes; P<0.001), in the length of ICU stay (19.5 +/- 17.8 versus 43 +/- 17.0 hours; P<0.001), time to extubation (4.6 +/- 6.8 versus 9.3 +/- 5.7 hours; P<0.001), hospital stay (6 +/- 2 versus 9 +/- 2 days; P<0.001), higher incidence of atrial fibrillation (35 versus 4% of patients; P<0.001), and blood requirements (31 versus 61% of patients; P<0.001), respectively. The number of grafts per patient was higher in the ONCAB than the OPCAB group (2.97 versus 2.49 grafts/patient; P<0.001). Conclusions-No difference was found between groups in the primary composite end point at 5-years follow-up. Although OPCAB surgery was related to a lower number of grafts and higher episodes of atrial fibrillation, it had no significant implications related to long-term outcomes.

VALIDATION OF THE LONDON CHEST ACTIVITY OF DAILY LIVING SCALE IN PATIENTS WITH HEART FAILURE

Background: The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is a well-validated, commonly-used tool to assess quality of life in patients with heart failure. However, it lacks specific information concerning breathlessness during daily activities. Objective: To determine the validity of the London Chest Activity of Daily Living (LCADL) scale for use in patients with heart failure. Methods: Forty-seven patients with heart failure (57% males, mean age 50 years (standard deviation 9), mean left ventricle ejection fraction 29% (SD 6), New York Heart Association (NYHA) functional class I-III) were included. All subjects first performed a cardiopulmonary exercise test and then responded to the LCADL and the MLHFQ, with guidance from the same investigator. The re-test for the LCADL was applied one week later. Results: LCADL was correlated with MLHFQ (r=0.88; p < 0.0001). LCADL and MLHFQ were also correlated with exercise capacity (r=-0.75 and r=-0.73, respectively; both p < 0.0001). The LCADL was shown to be reproducible (r(i)=0.98). There was a significant difference (p < 0.05) in the LCADL scores between NYHA functional classes I and II, as well as classes I and III, hut not between classes II and III. Conclusion: The LCADL was shown to be a valid measurement of dyspnoea during daily activities in patients with heart failure. This scale could be an additional useful tool for the assessment of patients` dyspnoea during activities of daily living.

Physical activity profile in heart failure patients from a Brazilian tertiary cardiology hospital

Background: Physical activity (PA) has proven benefits in the primary prevention of heart diseases such as heart failure (HF). Although it is well known, HF PA habits and physicians` advice have been poorly described. The aim of this study was to investigate if physicians were advising HF patients to exercise and to quantify patients` exercise profiles in a complex cardiology hospital. Methods: All 131 HF patients (80 male, average age 53 +/- 10 years, NYHA class I-V, left ventricular ejection fraction 35 +/- 11%, 35 ischemic, 35 idiopatic , 32 hypertensive and 29 with Chagas disease) went to the hospital for a HF routine check-up. On this occasion, after seeing the physician, we asked the patients if the physician had advised them about PA. Then, we asked them to fill in the international physical activity questionnaire (IPQA) Short Form to classify their PA level. Results: Our data showed a significant difference between patients who had received any kind of PA advice from physicians (36%) and those who had not (64%, p<0.0001). Using the IPAQ criteria, of the 36% of patients who had received advice, 12.4% were classified as low and 23.6% as moderate. Of the 64% of patients who did not receive advice, 26.8% were classified as lowand 37.2% as moderate. Etiology (except Chagas), functional class, ejection fraction, sex and age did not influence the PA profile. Conclusions: Physicians at a tertiary cardiology hospital were not giving patients satisfactory advice as to PA. Our data supports the need to strengthen exercise encouragement by physicians and for complementary studies on this area. (Cardiol J 2010; 17, 2: 143-148)

Effects of Exercise Training on Myocardial Blood Flow Reserve in Patients With Heart Failure and Left Ventricular Systolic Dysfunction

Exercise training has been shown to be effective in improving exercise capacity and quality of life in patients with heart failure and left ventricular (LV) systolic dysfunction. Real-time myocardial contrast echocardiography (RTMCE) is a new technique that allows quantitative analysis of myocardial blood flow (MBF). The aim of this study was to determine the effects of exercise training on MBF in patients with LV dysfunction. We studied 23 patients with LV dysfunction who underwent RTMCE and cardiopulmonary exercise testing at baseline and 4 months after medical treatment (control group, n = 10) or medical treatment plus exercise training (trained group, n = 13). Replenishment velocity (0) and MBF reserves were derived from quantitative RTMCE. The 4-month exercise training consisted of 3 60-minute exercise sessions/week at an intensity corresponding to anaerobic threshold, 10% below the respiratory compensation point. Aerobic exercise training did not change LV diameters, volumes, or ejection fraction. At baseline, no difference was observed in MBF reserve between the control and trained groups (1.89, 1.67 to 1.98, vs 1.81, 1.28 to 2.38, p = 0.38). Four-month exercise training resulted in a significant increase in beta reserve from 1.72 (1.45 to 1.48) to 2.20 (1.69 to 2.77, p <0.001) and an MBF reserve from 1.81 (1.28 to 2.38) to 3.05 (2.07 to 3.93, p <0.001). In the control group, 13 reserve decreased from 1.51 (1.10 to 1.85) to 1.46 (1.14 to 2.33, p = 0.03) and MBF reserve from 1.89 (1.67 to 1.98) to 1.55 (1.11 to 2.27, p <0.001). Peak oxygen consumption increased by 13.8% after 4 months of exercise training and decreased by 1.9% in the control group. In conclusion, exercise training resulted in significant improvement of MBF reserve in patients with heart failure and LV dysfunction. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:243-248)

The Carvedilol`s Beta-Blockade in Heart Failure and Exercise Training`s Sympathetic Blockade in Healthy Athletes during the Rest and Peak Effort

In recent years, beta-blocker therapy has become a primary pharmacologic intervention in patients with heart failure by blocking the sympathetic activity. To compare the exercise training`s sympathetic blockade in healthy subjects (athletes) and the carvedilol`s sympathetic blockade in sedentary heart failure patients by the evaluation of the heart rate dynamic during an exercise test. A total of 26 optimized and 49 nonoptimized heart failure patients in a stable condition (for, at least, 3 months), 15 healthy athletes and 17 sedentary healthy subjects were recruited to perform a cardiopulmonary exercise test. The heart rate dynamic (rest, reserve, peak and the peak heart rate in relation to the maximum predicted for age) was analyzed and compared between the four groups. The heart rate reserve was the same between optimized (48 +/- 15) and nonoptimized (49 +/- 18) heart failure patients (P < 0.0001). The athletes (188 +/- 9) showed a larger heart rate reserve compared to sedentary healthy subjects (92 +/- 10, P < 0.0001). Athletes and healthy sedentary reached the maximum age-predicted heart ratefor their age, but none of the heart failure patients did. The carvedilol`s sympathetic blockade occurred during the rest and during the peak effort in the same proportion, but the exercise training`s sympathetic blockade in healthy subjects occurred mainly in the rest.

Correlation between CD34(+) and exercise capacity, functional class, quality of life and norepinephrine in heart failure patients

Background: A previous study associated CD34(+) levels with NYHA functional class in heart failure patients. The aim of this study was to correlate CD34(+) levels to exercise capacity, functional class, quality of life and norepinephrine in heart failure patients. Methods: Twenty three sedentary patients (52 +/- 7 years, 78% male) answered the Minnesota Living with Heart Failure Questionnaire and rested for 20 minutes before an investigator collect a blood sample. After this, patients performed a cardiopulmonary exercise test to determine the heart rate at anaerobic and ventilatory threshold and oxygen consumption at peak effort, at anaerobic and ventilatory threshold. One other blood sample was collected during the peak effort to investigate the norepinephrine and CD34(+) levels. Results: Rest percentage of CD34(+) did not show correlation with: left ventricle ejection fraction (r = 0.03, p = 0.888), peakVO(2) (r = 0.32, p = 0.13), VO(2) at anaerobic threshold (VO(2)AT) (r = 0.03, p = 0.86), VO(2) at ventilatory threshold (VO(2)VT) (r = 0.36, p = 0.08), NYHA functional class (r = -0.2, p = 0.35), quality of life (Minnesota) (r = -0.17, p = 0.42). CD34(+) did not show correlation, either, with: peak VO(2) (r = 0.38, p = 0.06), VO(2)AT (r = 0.09, p = 0.65), VO(2)VT (r = 0.43, p = 0.4), NYHA functional class (r = -0.13, p = 0.54), quality of life (r = 0.00, p = 0.99). Conclusions: CD34(+) levels did not correlate with exercise capacity, functional class, quality of life and norepinephrine. Percentage of CD34(+) levels did not increase during the cardiopulmonary exercise test in heart failure patients. (Cardiol J 2009; 16, 5: 426-431)