J Fukushima

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, 9.0-9.2) 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.

Transfusion Requirements in Surgical Oncology Patients A Prospective, Randomized Controlled Trial

Background:Several studies have indicated that a restrictive erythrocyte transfusion strategy is as safe as a liberal one in critically ill patients, but there is no clear evidence to support the superiority of any perioperative transfusion strategy in patients with cancer. Methods:In a randomized, controlled, parallel-group, double-blind (patients and outcome assessors) superiority trial in the intensive care unit of a tertiary oncology hospital, the authors evaluated whether a restrictive strategy of erythrocyte transfusion (transfusion when hemoglobin concentration <7 g/dl) was superior to a liberal one (transfusion when hemoglobin concentration <9 g/dl) for reducing mortality and severe clinical complications among patients having major cancer surgery. All adult patients with cancer having major abdominal surgery who required postoperative intensive care were included and randomly allocated to treatment with the liberal or the restrictive erythrocyte transfusion strategy. The primary outcome was a composite endpoint of mortality and morbidity. Results:A total of 198 patients were included as follows: 101 in the restrictive group and 97 in the liberal group. The primary composite endpoint occurred in 19.6% (95% CI, 12.9 to 28.6%) of patients in the liberal-strategy group and in 35.6% (27.0 to 45.4%) of patients in the restrictive-strategy group (P = 0.012). Compared with the restrictive strategy, the liberal transfusion strategy was associated with an absolute risk reduction for the composite outcome of 16% (3.8 to 28.2%) and a number needed to treat of 6.2 (3.5 to 26.5). Conclusion:A liberal erythrocyte transfusion strategy with a hemoglobin trigger of 9 g/dl was associated with fewer major postoperative complications in patients having major cancer surgery compared with a restrictive strategy.

High lactate levels are predictors of major complications after cardiac surgery

OBJECTIVE Although hyperlactatemia after cardiac surgery is common, the implications of raised levels remain controversial. The aim of this study was to evaluate whether high lactate levels after cardiac surgery are predictors of major complications including mortality. PATIENTS AND METHODS This was a substudy of TRACS (Transfusion Requirements After Cardiac Surgery), which was designed as a prospective, randomized, controlled trial evaluating the effects of a transfusion strategy on morbidity and mortality. RESULTS Of the 502 patients enrolled, 52 (10%) had at least 1 major complication. Patients with complications were older, had a higher EuroSCORE, lower left ventricular ejection fraction, lower preoperative hemoglobin, a higher prevalence of renal disease, and received more blood transfusions than the group without complications. Lactate levels were higher in the group with complications at the end of surgery (3.6 mmol/L [2.8-5.1] vs 3.3 mmol/L [2.2-4.8]; P = .018), immediately after intensive care unit (ICU) admission (0 hour) (4.4 mmol/L [3.1-8.4] vs 4 mmol/L [2.6-6.4]; P = .048); 6 hours (4 mmol/L [2.7-5.8] vs 2.6 mmol/L [2-3.6], P < .001), and 12 hours after admission (2.3 mmol/L [1.8-3.2] vs 1.7 mmol/L [1.3-2]; P < .001). In a multivariate model, higher age (odds ratio [OR], 1.048, 95% confidence interval [CI], 1.011-1.086; P = .010), left ventricular ejection fraction (LVEF) lower than 40% (OR, 3.03; 95% CI, 1.200-7.510; P = .019 compared with LVEF of 40%-59%; OR, 3.571; 95% CI, 1.503-8.196; P = .004 compared with LVEF higher than 60%), higher EuroSCORE (OR, 1.138; 95% CI; 1.007-1.285; P = .038), red blood cell transfusion (OR, 1.230; 95% CI, 1.086-1.393; P = .001), and lactate levels 6 hours after ICU admission (OR, 3.28, 95% CI; 1.61-6.69; P = .001) are predictors of major complications. CONCLUSIONS Hyperlactatemia 6 hours after ICU admission is an independent risk factor for worse outcomes in adult patients after cardiac surgery.

Effect of Perioperative Goal-Directed Hemodynamic Resuscitation Therapy on Outcomes Following Cardiac Surgery: A Randomized Clinical Trial and Systematic Review.

Objectives:To evaluate the effects of goal-directed therapy on outcomes in high-risk patients undergoing cardiac surgery. Design:A prospective randomized controlled trial and an updated metaanalysis of randomized trials published from inception up to May 1, 2015. Setting:Surgical ICU within a tertiary referral university-affiliated teaching hospital. Patients:One hundred twenty-six high-risk patients undergoing coronary artery bypass surgery or valve repair. Interventions:Patients were randomized to a cardiac output–guided hemodynamic therapy algorithm (goal-directed therapy group, n = 62) or to usual care (n = 64). In the goal-directed therapy arm, a cardiac index of greater than 3 L/min/m2 was targeted with IV fluids, inotropes, and RBC transfusion starting from cardiopulmonary bypass and ending 8 hours after arrival to the ICU. Measurements and Main Results:The primary outcome was a composite endpoint of 30-day mortality and major postoperative complications. Patients from the goal-directed therapy group received a greater median (interquartile range) volume of IV fluids than the usual care group (1,000 [625–1,500] vs 500 [500–1,000] mL; p < 0.001], with no differences in the administration of either inotropes or RBC transfusions. The primary outcome was reduced in the goal-directed therapy group (27.4% vs 45.3%; p = 0.037). The goal-directed therapy group had a lower occurrence rate of infection (12.9% vs 29.7%; p = 0.002) and low cardiac output syndrome (6.5% vs 26.6%; p = 0.002). We also observed lower ICU cumulative dosage of dobutamine (12 vs 19 mg/kg; p = 0.003) and a shorter ICU (3 [3–4] vs 5 [4–7] d; p < 0.001) and hospital length of stay (9 [8–16] vs 12 [9–22] d; p = 0.049) in the goal-directed therapy compared with the usual care group. There were no differences in 30-day mortality rates (4.8% vs 9.4%, respectively; p = 0.492). The metaanalysis identified six trials and showed that, when compared with standard treatment, goal-directed therapy reduced the overall rate of complications (goal-directed therapy, 47/410 [11%] vs usual care, 92/415 [22%]; odds ratio, 0.40 [95% CI, 0.26–0.63]; p < 0.0001) and decreased the hospital length of stay (mean difference, –5.44 d; 95% CI, –9.28 to –1.60; p = 0.006) with no difference in postoperative mortality: 9 of 410 (2.2%) versus 15 of 415 (3.6%), odds ratio, 0.61 (95% CI, 0.26–1.47), and p = 0.27. Conclusions:Goal-directed therapy using fluids, inotropes, and blood transfusion reduced 30-day major complications in high-risk patients undergoing cardiac surgery.

Vasopressin versus Norepinephrine in Patients with Vasoplegic Shock After Cardiac Surgery: The VANCS Randomized Controlled Trial.

Background: Vasoplegic syndrome is a common complication after cardiac surgery and impacts negatively on patient outcomes. The objective of this study was to evaluate whether vasopressin is superior to norepinephrine in reducing postoperative complications in patients with vasoplegic syndrome. Methods: This prospective, randomized, double-blind trial was conducted at the Heart Institute, University of Sao Paulo, Sao Paulo, Brazil, between January 2012 and March 2014. Patients with vasoplegic shock (defined as mean arterial pressure less than 65 mmHg resistant to fluid challenge and cardiac index greater than 2.2 l · min−1 · m−2) after cardiac surgery were randomized to receive vasopressin (0.01 to 0.06 U/min) or norepinephrine (10 to 60 &mgr;g/min) to maintain arterial pressure. The primary endpoint was a composite of mortality or severe complications (stroke, requirement for mechanical ventilation for longer than 48 h, deep sternal wound infection, reoperation, or acute renal failure) within 30 days. Results: A total of 330 patients were randomized, and 300 were infused with one of the study drugs (vasopressin, 149; norepinephrine, 151). The primary outcome occurred in 32% of the vasopressin patients and in 49% of the norepinephrine patients (unadjusted hazard ratio, 0.55; 95% CI, 0.38 to 0.80; P = 0.0014). Regarding adverse events, the authors found a lower occurrence of atrial fibrillation in the vasopressin group (63.8% vs. 82.1%; P = 0.0004) and no difference between groups in the rates of digital ischemia, mesenteric ischemia, hyponatremia, and myocardial infarction. Conclusions: The authors’ results suggest that vasopressin can be used as a first-line vasopressor agent in postcardiac surgery vasoplegic shock and improves clinical outcomes.

Positive fluid balance is associated with reduced survival in critically ill patients with cancer

There are no studies that describe the impact of the cumulative fluid balance on the outcomes of cancer patients admitted to intensive care units ICUs. The aim of our study was to evaluate the relationship between fluid balance and clinical outcomes in these patients.

Hemostatic effects of fibrinogen concentrate compared with cryoprecipitate in children after cardiac surgery: A randomized pilot trial

OBJECTIVES Acute acquired hypofibrinogenemia in children undergoing cardiac surgery is a major concern because it often results in perioperative bleeding and high rates of allogeneic blood transfusion. Fibrinogen concentrate has been proposed as an alternative to cryoprecipitate (the gold standard therapy), with minimal infectious and immunologic risks. Our objective was to investigate the efficacy and safety of fibrinogen concentrate in children undergoing cardiac surgery. METHODS In this randomized pilot study, patients were allocated to receive fibrinogen concentrate (60 mg/kg) or cryoprecipitate (10 mL/kg) if bleeding was associated with fibrinogen levels<1 g/dL after cardiopulmonary bypass weaning. The primary outcome was postoperative blood losses during the 48 hours after surgery. RESULTS A total of 63 patients were included in the study, 30 in the fibrinogen concentrate group and 33 in the cryoprecipitate group. The median 48-hour blood loss was not significantly different between the 2 groups (320 mL [interquartile range, 157-750] vs 410 mL [interquartile range, 215-510], respectively; P=.672). After treatment, plasma fibrinogen concentration increased similarly following administration of both products. There were no differences in allogeneic blood transfusion after intervention treatment. CONCLUSIONS A large trial comparing fibrinogen concentrate and cryoprecipitate in the management of children with acute acquired hypofibrinogenemia during heart surgery is feasible. The preliminary results of our study showed that the use of fibrinogen concentrate was as efficient and safe as cryoprecipitate in the management of bleeding children undergoing cardiac surgery.

Volume replacement therapy during hip arthroplasty using hydroxyethyl starch (130/0.4) compared to lactated Ringer decreases allogeneic blood transfusion and postoperative infection

BACKGROUND AND OBJECTIVES Hydroxyethyl starch (HES) 130/0.4 is considered an effective plasma expander when compared to crystalloids. There is controversy around its superiority regarding hemodynamic optimization and about possible detrimental effects on coagulation. The aim of this study was to compare the effects of HES 130/0.4 to lactated Ringer solution during hip arthroplasty in adult patients under spinal anesthesia regarding intraoperative bleeding, hemodynamic parameters, coagulation profile, transfusion requirements and clinical outcomes. METHODS In this randomized, controlled trial, 48 patients scheduled for hip arthroplasty with spinal anesthesia were randomized into two groups: 24 patients were allocated to receive a preload of 15 mL.kg(-1) of HES 130/0.4 and 24 patients received a preload of 30 mL.kg(-1) lactated Ringer solution before surgery. Hemodynamic measurements, hemoglobin concentrations, biochemical parameters and coagulation tests were evaluated in three periods during surgical procedure. Patients received medical follow-up during their hospital stay and up to postoperative 30 days. Primary outcome was the requirement of red blood cell transfusion between groups during hospital stay. Secondary outcome were hemodynamic parameters, length of hospital stay, mortality and occurrence of clinical postoperative complications. RESULTS Red blood cell transfusion was required in 17% of patients in the HES group and in 46% in the Ringer group (p = .029). Postoperative infections were more frequently observed in the Ringer group (17%) compared to the HES group (0), p = .037. There were no significant differences between groups in mortality, hospital length of stay and clinical complications other than infection. CONCLUSIONS During hip arthroplasty, patients treated with hypervolemic hemodilution with hydroxyethyl starch 130/0.4 required less transfusion and presented lower infection rate compared to patients who received lactated Ringer.

Liberal Versus Restrictive Transfusion Strategy in Critically Ill Oncologic Patients: The Transfusion Requirements in Critically Ill Oncologic Patients Randomized Controlled Trial*

Objective: To assess whether a restrictive strategy of RBC transfusion reduces 28-day mortality when compared with a liberal strategy in cancer patients with septic shock. Design: Single center, randomized, double-blind controlled trial. Setting: Teaching hospital. Patients: Adult cancer patients with septic shock in the first 6 hours of ICU admission. Interventions: Patients were randomized to the liberal (hemoglobin threshold, < 9 g/dL) or to the restrictive strategy (hemoglobin threshold, < 7 g/dL) of RBC transfusion during ICU stay. Measurements and Main Results: Patients were randomized to the liberal (n = 149) or to the restrictive transfusion strategy (n = 151) group. Patients in the liberal group received more RBC units than patients in the restrictive group (1 [0–3] vs 0 [0–2] unit; p < 0.001). At 28 days after randomization, mortality rate in the liberal group (primary endpoint of the study) was 45% (67 patients) versus 56% (84 patients) in the restrictive group (hazard ratio, 0.74; 95% CI, 0.53–1.04; p = 0.08) with no differences in ICU and hospital length of stay. At 90 days after randomization, mortality rate in the liberal group was lower (59% vs 70%) than in the restrictive group (hazard ratio, 0.72; 95% CI, 0.53–0.97; p = 0.03). Conclusions: We observed a survival trend favoring a liberal transfusion strategy in patients with septic shock when compared with the restrictive strategy. These results went in the opposite direction of the a priori hypothesis and of other trials in the field and need to be confirmed.

Oncologic Concerns regarding Laparoscopic Cytoreductive Surgery in Patients with Advanced Ovarian Cancer Submitted to Neoadjuvant Chemotherapy

Background: Presently, the use of laparoscopy in advanced ovarian cancer (AOC) is extremely controversial. In the era of neoadjuvant chemotherapy (NACT), endoscopic debulking surgery could be a reasonable alternative for selected patients with primarily unresectable disease. Objectives: To evaluate the feasibility as well as the operative and oncologic safety of laparoscopic debulking surgery in patients with AOC submitted to NACT. Methods: This is a pilot observational study on initially unresectable, high-grade serous ovarian cancer treated with a sequence of 6 cycles of carboplatin and paclitaxel followed by debulking surgery performed by laparoscopy (group 1) or laparotomy (group 2). The inclusion criteria were clinical complete response, CA-125 normalization, imaging without disease in critical areas, and optimal cytoreduction. Results: From January 2011 to March 2014, 21 patients were included. Ten women underwent laparoscopy and 11 laparotomy. No epidemiological or oncologic differences were observed between the groups. No surgery-related casualties, intraoperative complications, conversion to laparotomy, or excessive blood loss or transfusion was detected in the laparoscopic procedures. The mean time of operation was 292 min. The length of hospital stay averaged 3.6 days. Two women in group 1 developed relevant complications. After a mean follow-up of 20 months, the recurrence rates were similar, i.e. 80% in group 1 versus 88% in group 2. Although statistical significance was not reached, the mortality related to cancer was considerably higher (20 vs. 0%; p = 0.086) and the mean chemotherapy-free interval was markedly shorter in group 1 (13.3 vs. 20.5 months; p = 0.288). Conclusion: Laparoscopic optimal debulking surgery after NACT is feasible and effective in selected patients. Nevertheless, laparoscopy was substantially associated with inferior oncologic results. Endoscopic cytoreduction in AOC should be cautiously suggested until larger prospective trials confirm the observed results.