Abstract

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.).

Abstract

The use of colloids may impair hemostatic capacity. However, it remains unclear whether this also holds true when colloids are administered in a goal-directed manner. The aim of the present study was to assess the effect of goal-directed fluid management with 6% hydroxyethyl starch 130/0.4 on hemostasis compared to lactated Ringer's solution in patients undergoing partial hepatectomy. We included 50 patients in this prospective, randomized, controlled trial. According to randomization, patients received boluses of either hydroxyethyl starch or lactated Ringer's solution within the scope of goal-directed fluid management. Minimum perioperative FIBTEM maximum clot firmness (MCF) served as the primary outcome parameter. Secondary outcome parameters included fibrinogen levels and estimated blood loss. In the hydroxyethyl starch (HES) group the minimum FIBTEM MCF value was significantly lower (effect size -6 mm, 95% CI -10 to -3, p < 0.001) in comparison to the lactated Ringer's solution (RL) group. These results returned to normal within 24 h. We observed no difference in plasma fibrinogen levels (RL 3.08 ± 0.37 g L(-1) vs HES 2.65 ± 0.64 g L(-1), p = 0.18) or the amount of blood loss between the two groups (RL 470 ± 299 mL vs HES 604 ± 351 mL, p = 0.18). We showed that goal-directed use of HES impairs fibrin polymerization in a dose-dependent manner when compared with RL. Results returned to normal on the first postoperative day without administration of procoagulant drugs and no differences in blood loss were observed.

Abstract

BACKGROUND N-terminal pro brain natriuretic peptide (NT-proBNP) and troponin T are released during myocardial wall stress and/or ischemia and are strong predictors for postoperative cardiovascular complications. However, the relative effects of goal-directed, intravenous administration of crystalloid compared to colloid solutions on NT-proBNP and troponin T, especially in relatively healthy patients undergoing moderate- to high-risk noncardiac surgery, remains unclear. Thus, we evaluated in this sub-study the effect of a goal-directed crystalloid versus a goal-directed colloid fluid regimen on postoperative maximum NT-proBNP concentration. We further evaluated the incidence of myocardial injury after noncardiac surgery (MINS) between both study groups. METHODS Thirty patients were randomly assigned to receive additional intravenous fluid boluses of 6% hydroxyethyl starch 130/0.4 and 30 patients to receive lactated Ringer's solution. Intraoperative fluid management was guided by oesophageal Doppler-according to a previously published algorithm. The primary outcome were differences in postoperative maximum NT-proBNP (maxNT-proBNP) between both groups. As our secondary outcome we evaluated the incidence of MINS between both study groups. We defined maxNT-proBNP as the maximum value measured within 2 h after surgery and on the first and second postoperative day. RESULTS In total 56 patients were analysed. There was no significant difference in postoperative maximum NT-proBNP between the colloid group (258.7 ng/L (IQR 199.4 to 782.1)) and the crystalloid group (440.3 ng/L (IQR 177.9 to 691.2)) during the first 2 postoperative days (P = 0.29). Five patients in the colloid group and 7 patients in the crystalloid group developed MINS (P = 0.75). CONCLUSIONS Based on this relatively small study goal-directed colloid administration did not decrease postoperative maxNT-proBNP concentration as compared to goal-directed crystalloid administration. TRIAL REGISTRATION ClinicalTrials.gov ( NCT01195883 ) Registered on 6th September 2010.

Abstract

BACKGROUND Excessive perioperative fluid administration may result in iatrogenic endothelial dysfunction and tissue edema, transducing inflammatory markers into the bloodstream. Colloids remain longer in the circulation, requiring less volume to reach similar hemodynamic endpoints compared to crystalloids. Thus, we tested the hypothesis that a goal-directed colloid regimen attenuates the inflammatory response compared to a goal-directed crystalloid regime. METHODS Patients undergoing moderate- to high-risk open abdominal surgery were randomly assigned to goal-directed lactated Ringer's solution (n = 58) or a hydroxyethyl starch 6% 130/0.4 (n = 62) fluid regimen. Our primary outcome was perioperative levels of pro- and anti-inflammatory cytokines. Secondary outcome was perioperative levels of white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT) and lipopolysaccharide-binding protein (LBP). Measurements were performed preoperatively, immediate postoperatively, on postoperative day one, two and four. RESULTS The areas under the curve of Interleukin (IL) 6 (p = 0.60), IL 8 (p = 0.46), IL 10 (p = 0.68) and tumor necrosis factor α (p = 0.47) levels did not differ significantly between the groups. WBC, CRP and PCT values were also comparable. LBP, although significantly higher in the crystalloid group, remained in the normal range. Patients assigned to crystalloids received a median (IQR) amount of 3905 mL (2880-5288) of crystalloid. Patients assigned to colloids received 1557 mL (1207-2116) of crystalloid and 1250 mL (750-1938) of colloid. CONCLUSION Cytokine and inflammatory marker levels did not differ between goal-directed crystalloid and colloid administration after moderate to high-risk abdominal surgery. TRIAL REGISTRATION ClinicalTrials.gov ( NCT00517127 ). Registered 16th August 2007.

Abstract

BACKGROUND Sufficient tissue oxygen tension may reduce the risk of postoperative wound infections. Supplemental administration of crystalloids increases subcutaneous oxygen tension (Psqo2). Colloids remain longer in the intravascular system and might therefore increase Psqo2 even more than crystalloids. Therefore, we tested the hypothesis that goal-directed colloid administration increases the perioperative Psqo2 more compared with crystalloid administration. METHODS We randomly assigned 80 patients undergoing elective open abdominal surgery to receive fluid boluses of hydroxyethyl starch (HES) or lactated Ringer's (LR) solution guided by oesophageal Doppler. Intraoperative Psqo2 was measured in the upper arm. After operation, we measured the Psqo2 in the upper arm and in the surgical wound. RESULTS Forty patients were enrolled in each group. Patients in the colloid group received HES solution 750 ml (500; 1000) and LR solution 1500 ml (1000; 2000). Patients in the crystalloid group received LR solution 2825 ml (2000; 3960). The goal-directed administration of colloids did not improve intraoperative Psqo2 in the arm compared with crystalloid administration (11.4 kPa [9.0; 16.6] vs 11.2 kPa [8.6; 15.1], respectively; P=0.58). Postoperative arm Psqo2 was 8.1 kPa (6.5; 9.6) in the colloid group and 7.3 kPa (5.7; 9.1) in the crystalloid group (P=0.11). Postoperative surgical wound Psqo2 was 10.7 kPa (8.6; 13.4) in the colloid group and 10.1 kPa (8.1; 12.7) in the crystalloid group (P=0.68). CONCLUSIONS Goal-directed colloid administration did not increase Psqo2 compared with goal-directed crystalloid administration in patients undergoing open abdominal surgery. CLINICAL TRIAL REGISTRATION NCT00517127.

Abstract

WHAT WE ALREADY KNOW ABOUT THIS TOPIC Crystalloid solutions leave the circulation quickly, whereas colloids remain for hours, thus promoting hemodynamic stability. However, colloids are expensive and promote renal toxicity in critical care patients. Whether goal-directed intraoperative tetrastarch colloid administration reduces complications or promotes renal injury remains unknown. WHAT THIS ARTICLE TELLS US THAT IS NEW In a large randomized trial comparing intraoperative goal-directed 6% hydroxyethyl starch with goal-directed lactated Ringer's solution in patients having major abdominal surgery, 6% hydroxyethyl starch reduced neither a composite of serious complications nor the duration of hospitalization. However, 6% hydroxyethyl starch did not cause acute or long-term renal toxicity. BACKGROUND Crystalloid solutions leave the circulation quickly, whereas colloids remain for hours, thus promoting hemodynamic stability. However, colloids are expensive and promote renal toxicity in critical care patients. This study tested the hypothesis that goal-directed colloid administration during elective abdominal surgery decreases 30-day major complications more than goal-directed crystalloid administration. METHODS In this parallel-arm double-blinded multicenter randomized trial, adults having moderate- to high-risk open and laparoscopically assisted abdominal surgery with general anesthesia were randomly assigned to Doppler-guided intraoperative volume replacement with 6% hydroxyethyl starch 130/0.4 (n = 523) or lactated Ringer's solution (n = 534). The primary outcome was a composite of serious postoperative cardiac, pulmonary, infectious, gastrointestinal, renal, and coagulation complications that were assessed with a generalized estimating equation multivariate model. The primary safety outcome was a change in serum creatinine concentration up to 6 months postoperatively, compared to baseline concentrations. RESULTS A total of 1,057 patients were included in the analysis. Patients assigned to crystalloid received a median [quartile 1, quartile 3] amount of 3.2 l [2.3, 4.4] of crystalloid, and patients assigned to colloid received 1.0 l [0.5, 1.5] of colloid and 1.8 l [1.2, 2.4] of crystalloid. The estimated intention-to-treat common effect relative risk for the primary composite was 0.90 for colloids versus crystalloids (95% CI: 0.65 to 1.23, P = 0.51), and 18% (91 of 523) of colloid patients and 20% (103 of 534) of crystalloid patients incurred at least one component of the primary outcome composite. There was no evidence of renal toxicity at any time. CONCLUSIONS Doppler-guided intraoperative hydroxyethyl starch administration did not significantly reduce a composite of serious complications. However, there was also no indication of renal or other toxicity.