J Iribarren

Clinical cure of ventilator-associated pneumonia treated with piperacillin/tazobactam administered by continuous or intermittent infusion.

The standard mode of administration of piperacillin treatment is by intermittent infusion. However, continuous infusion may be advantageous as beta-lactam antibiotics exhibit time-dependent antibacterial activity. In previous studies, we found a higher rate of clinical cure of ventilator-associated pneumonia (VAP) by continuous infusion rather than intermittent infusion of meropenem and ceftazidime. Therefore, the objective of this historical cohort study was to establish the clinical efficacy of piperacillin/tazobactam (PIP/TAZ) administered by continuous and intermittent infusion in the treatment of VAP in patients without renal failure. Logistic regression analysis showed a higher probability of clinical cure of VAP by continuous compared with intermittent infusion when the microorganism responsible for VAP had a minimum inhibitory concentration (MIC) of 8 microg/mL [8/9 (88.9%) vs. 6/15 (40.0%); odds ratio (OR)=10.79, 95% confidence interval (CI) 1.01-588.24; P=0.049] or 16 microg/mL [7/8 (87.5%) vs. 1/6 (16.7%); OR=22.89, 95% CI 1.19-1880.78; P=0.03]. Thus, administration of PIP/TAZ by continuous infusion may be considered more effective than intermittent infusion for the treatment of VAP caused by Gram-negative bacteria when the MIC of the microorganism responsible for VAP is 8-16 microg/mL in patients without renal failure.

Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: a case control study followed by a randomized double-blind controlled trial

IntroductionExtracorporeal circulation induces hemostatic alterations that lead to inflammatory response (IR) and postoperative bleeding. Tranexamic acid (TA) reduces fibrinolysis and blood loss after cardiopulmonary bypass (CPB). However, its effects on IR and vasoplegic shock (VS) are not well known and elucidating these effects was the main objective of this study.MethodsA case control study was carried out to determine factors associated with IR after CPB. Patients undergoing elective CPB surgery were randomly assigned to receive 2 g of TA or placebo (0.9% saline) before and after intervention. We performed an intention-to-treat analysis, comparing the incidence of IR and VS. We also analyzed several biological parameters related to inflammation, coagulation, and fibrinolysis systems. We used SPSS version 12.2 for statistical purposes.ResultsIn the case control study, 165 patients were studied, 20.6% fulfilled IR criteria, and the use of TA proved to be an independent protective variable (odds ratio 0.38, 95% confidence interval 0.18 to 0.81; P < 0.01). The clinical trial was interrupted. Fifty patients were randomly assigned to receive TA (24) or placebo (26). Incidence of IR was 17% in the TA group versus 42% in the placebo group (P = 0.047). In the TA group, we observed a significant reduction in the incidence of VS (P = 0.003), the use of norepinephrine (P = 0.029), and time on mechanical ventilation (P = 0.018). These patients showed significantly lower D-dimer, plasminogen activator inhibitor 1, and creatine-kinase levels and a trend toward lower levels of soluble tumor necrosis factor receptor and interleukin-6 within the first 24 hours after CPB.ConclusionThe use of TA attenuates the development of IR and VS after CPB.Trial registration numberISRCTN05718824.

Microorganisms responsible for intravascular catheter-related bloodstream infection according to the catheter site.

Objective:Current guidelines for the management of intravascular catheter-related bloodstream infection (IVC-RBSI) recommend that empirical antimicrobial therapy must have activity against Gram-positive bacteria, but additional empirical coverage for Gram-negative bacteria may be needed for severely ill or immunocompromised patients, and antifungal therapy may be needed in some situations. We hypothesized that the spectrum of etiological microorganisms responsible for IVC-RBSI and, in relation to that, the choice of empirical antimicrobial therapy depends on the catheter insertion site. We therefore compared the proportion of IVC-RBSI due to Gram-negative bacteria and yeasts according to catheter site. Design:Prospective cohort study from May 1, 2000, to April 30, 2004. Setting:A 24-bed medical-surgical intensive care unit in a 650-bed tertiary hospital. Patients:Patients requiring a central venous or arterial catheter. Measurements and Main Results:We diagnosed 88 IVC-RBSIs, comprising 36 femoral catheter sites (26 femoral venous and ten femoral arterial sites) and 52 other catheter sites (36 jugular venous, 11 subclavian venous, and five radial arterial sites). No differences were found between IVC-RBSI of femoral vs. other catheter sites for age, sex, Acute Physiology and Chronic Health Evaluation II, diagnosis at admission, use of antimicrobials, the time the catheter responsible for IVC-RBSI had been in place, or the duration of intensive care unit stay before IVC-RBSI. The proportion of IVC-RBSIs due to Gram-negative bacteria was higher in femoral, 14 of 36 (38.89%), than in the other catheter sites, 4 of 52 (7.69%) (odds ratio, 7.48; 95% confidence interval, 2.19–25.54; p = .001). Also, the proportion of IVC-RBSIs due to yeasts was higher in femoral, 6 of 36 (16.67%), than in the other catheter sites, 1 of 52 (1.92%) (odds ratio, 10.20; 95% confidence interval, 1.17–88.85; p = .035). Conclusions:Empirical antifungal therapy would seem to be indicated in patients with suspected femoral catheter-related bloodstream infection.

Factors associated with excessive bleeding in cardiopulmonary bypass patients: a nested case-control study

IntroductionExcessive bleeding (EB) after cardiopulmonary bypass (CPB) may lead to increased mortality, morbidity, transfusion requirements and re-intervention. Less than 50% of patients undergoing re-intervention exhibit surgical sources of bleeding. We studied clinical and genetic factors associated with EB.MethodsWe performed a nested case-control study of 26 patients who did not receive antifibrinolytic prophylaxis. Variables were collected preoperatively, at intensive care unit (ICU) admission, at 4 and 24 hours post-CPB. EB was defined as 24-hour blood loss of >1 l post-CPB. Associations of EB with genetic, demographic, and clinical factors were analyzed, using SPSS-12.2 for statistical purposes.ResultsEB incidence was 50%, associated with body mass index (BMI)< 26.4 (25–28) Kg/m2, (P = 0.03), lower preoperative levels of plasminogen activator inhibitor-1 (PAI-1) (P = 0.01), lower body temperature during CPB (P = 0.037) and at ICU admission (P = 0.029), and internal mammary artery graft (P = 0.03) in bypass surgery. We found a significant association between EB and 5G homozygotes for PAI-1, after adjusting for BMI (F = 6.07; P = 0.02) and temperature during CPB (F = 8.84; P = 0.007). EB patients showed higher consumption of complement, coagulation, fibrinolysis and hemoderivatives, with significantly lower leptin levels at all postoperative time points (P = 0.01, P < 0.01 and P < 0.01).ConclusionExcessive postoperative bleeding in CPB patients was associated with demographics, particularly less pronounced BMI, and surgical factors together with serine protease activation.

Safety and Effectiveness of two treatment regimes with tranexamic acid to minimize inflammatory response in elective cardiopulmonary bypass patients: a randomized double-blind, dose-dependent, phase IV clinical trial

BackgroundIn cardiopulmonary bypass (CPB) patients, fibrinolysis may enhance postoperative inflammatory response. We aimed to determine whether an additional postoperative dose of antifibrinolytic tranexamic acid (TA) reduced CPB-mediated inflammatory response (IR).MethodsWe performed a randomized, double-blind, dose-dependent, parallel-groups study of elective CPB patients receiving TA. Patients were randomly assigned to either the single-dose group (40 mg/Kg TA before CPB and placebo after CPB) or the double-dose group (40 mg/Kg TA before and after CPB).Results160 patients were included, 80 in each group. The incident rate of IR was significantly lower in the double-dose-group TA2 (7.5% vs. 18.8% in the single-dose group TA1; P = 0.030). After adjusting for hypertension, total protamine dose and temperature after CPB, TA2 showed a lower risk of IR compared with TA1 [OR: 0.29 (95% CI: 0.10-0.83), (P = 0.013)]. Relative risk for IR was 2.5 for TA1 (95% CI: 1.02 to 6.12). The double-dose group had significantly lower chest tube bleeding at 24 hours [671 (95% CI 549-793 vs. 826 (95% CI 704-949) mL; P = 0.01 corrected-P significant] and lower D-dimer levels at 24 hours [489 (95% CI 437-540) vs. 621(95% CI: 563-679) ng/mL; P = 0.01 corrected-P significant]. TA2 required lower levels of norepinephrine at 24 h [0.06 (95% CI: 0.03-0.09) vs. 0.20(95 CI: 0.05-0.35) after adjusting for dobutamine [F = 6.6; P = 0.014 corrected-P significant].We found a significant direct relationship between IL-6 and temperature (rho = 0.26; P < 0.01), D-dimer (rho = 0.24; P < 0.01), norepinephrine (rho = 0.33; P < 0.01), troponin I (rho = 0.37; P < 0.01), Creatine-Kinase (rho = 0.37; P < 0.01), Creatine Kinase-MB (rho = 0.33; P < 0.01) and lactic acid (rho = 0.46; P < 0.01) at ICU arrival. Two patients (1.3%) had seizure, 3 patients (1.9%) had stroke, 14 (8.8%) had acute kidney failure, 7 (4.4%) needed dialysis, 3 (1.9%) suffered myocardial infarction and 9 (5.6%) patients died. We found no significant differences between groups regarding these events.ConclusionsProlonged inhibition of fibrinolysis, using an additional postoperative dose of tranexamic acid reduces inflammatory response and postoperative bleeding (but not transfusion requirements) in CPB patients. A question which remains unanswered is whether the dose used was ideal in terms of safety, but not in terms of effectiveness.Current Controlled Trials numberISRCTN: ISRCTN84413719

The micro-organism responsible for central venous catheter related bloodstream infection depends on catheter site.

Sir: Although the micro-organism responsible for central venous catheter related bloodstream infection (CVCRBSI) have been amply reported [1, 2, 3], we have found no study reporting the micro-organism responsible according to the three catheter sites (femoral, jugular, and subclavian). We therefore analyzed this issue as a part of our recently published study [4]. In a first analysis of 1,277 CVC inserted over 18 months we found no significant differences in CVC-RBSI incidence between sites [5]. In a second analysis of

Postoperative bleeding in cardiac surgery: the role of tranexamic acid in patients homozygous for the 5G polymorphism of the plasminogen activator inhibitor-1 gene.

Background:Plasminogen activator inhibitor 1 (PAI-1) attenuates the conversion of plasminogen to plasmin. Polymorphisms of the PAI-1 gene are associated with varying PAI-1 levels and risk of prothrombotic events in nonsurgical patients. The purpose of this study, a secondary analysis of a clinical trial, was to investigate whether PAI-1 genotype affects the efficacy of tranexamic acid (TA) in reducing postoperative chest tube blood loss of patients undergoing cardiopulmonary bypass. Methods:Fifty patients were classified according to PAI-1 genotype (4G/4G, 4G/5G, or 5G/5G). Twenty-four received 2 g TA before and after cardiopulmonary bypass, whereas 26 received placebo. The authors recorded data related to coagulation, fibrinolysis, and bleeding before surgery, at admission to the intensive care unit (0 h), and 4 and 24 h later. Results:In patients not receiving TA, those with the 5G/5G genotype had significantly higher chest tube blood loss and transfusion requirements compared with patients with the other genotypes at all time points. Patients with the 5G/5G genotype receiving TA showed significantly lower blood loss compared with the placebo group. There were no significant differences in blood loss or transfusion requirements between patients with the 4G/4G genotype when TA was used. Conclusions:Plasminogen activator inhibitor-1 5G/5G homozygotes who did not receive TA showed significantly greater postoperative bleeding than patients with other PAI-1 genotypes. 5G/5G homozygotes who received TA showed the greatest blood-sparing benefit.

Relative adrenal insufficiency and hemodynamic status in cardiopulmonary bypass surgery patients. A prospective cohort study

BackgroundThe objectives of this study were to determine the risk factors for relative adrenal insufficiency in cardiopulmonary bypass patients and the impact on postoperative vasopressor requirements.MethodsProspective cohort study on cardiopulmonary bypass patients who received etomidate or not during anesthetic induction. Relative adrenal insufficiency was defined as a rise in serum cortisol ≤ 9 μg/dl after the administration of 250 μg of consyntropin. Plasma cortisol levels were measured preoperatively, immediately before, 30, 60, and 90 minutes after the administration of cosyntropin, and at 24 hours after surgery.Results120 elective cardiopulmonary bypass patients were included. Relative adrenal insufficiency (Δcortisol ≤9 μg/dl) incidence was 77.5%. 78 patients received etomidate and 69 (88%) of them developed relative adrenal insufficiency, (P < 0.001). Controlling for clinical characteristics with a propensity analysis, etomidate was the only independent risk factor associated with relative adrenal insufficiency (OR 6.55, CI 95%: 2.47-17.4; P < 0.001). Relative adrenal insufficiency patients showed more vasopressor requirements just after surgery (P = 0.04), and at 4 hours after surgery (P = 0.01). Pre and post-test plasma cortisol levels were inversely associated with maximum norepinephrine dose (ρ = -0.22, P = 0.02; ρ = -0.18, P = 0.05; ρ = -0.21, P = 0.02; and ρ = -0.22, P = 0.02, respectively).ConclusionsRelative adrenal insufficiency in elective cardiopulmonary bypass patients may induce postoperative vasopressor dependency. Use of etomidate in these patients is a modifiable risk factor for the development of relative adrenal insufficiency that should be avoided.

The catheter site influences in the micro-organism responsible of arterial catheter-related infection.

Sir: Although arterial catheter-related infection (AC-RI) has been amply reported [1, 2], we have found no study reporting the micro-organisms responsible according to femoral and radial access. We therefore analyzed this as a part of our recently published study [3], such as we have lately done with central venous catheter-related infection [4]. An initial analysis of 1,231 arterial catheters inserted during 18months revealed no significant differences in the incidence of arterial catheter-related bloodstream infections (AC-RBSI) and of arterial catheter-related local infections (ACRLI) according to catheter site [5]. In a second analysis of 2,949 arterial catheters inserted over 3 years, however, we found that the incidence

Higher arterial catheter-related infection rates in femoral than in dorsalis pedis access.

Although there are many studies on arterial catheter-related infection (ACRI) there is little information on the relative risks associated with different catheter access sites. In previous studies we have shown a higher incidence of ACRI in femoral than in radial access sites. This prospective observational study was designed to compare the incidence of ACRI in patients on an intensive care unit with femoral versus dorsalis pedis access sites. We compared 1085 femoral arterial catheters inserted for a cumulative 6497 days with 174 dorsalis pedis catheters inserted for a cumulative 1050 days. We detected 33 cases of ACRI in the femoral access group (11 with bacteraemia and 22 with line site infection; 5.08 infections per 1000 catheter-days) but none in the dorsalis pedis access group. There were no significant differences between the two groups regarding age, sex, Acute Physiological Assessment and Chronic Health Evaluation (APACHE) II, diagnosis, previous arterial catheter insertion, use of mechanical ventilation, use of antimicrobials or catheter duration. Regression analysis showed a higher incidence of ACRI for femoral than for dorsalis pedis access sites (odds ratio: 7.6; 95% confidence interval: 1.37-infinite; P=0.01). These results suggest that dorsalis pedis arterial access should be used in preference to femoral arterial access in order to reduce the risk of ACRI.