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      Cardiac ischemia in patients with septic shock randomized to vasopressin or norepinephrine

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          Abstract

          Introduction

          Cardiac troponins are sensitive and specific biomarkers of myocardial necrosis. We evaluated troponin, CK, and ECG abnormalities in patients with septic shock and compared the effect of vasopressin (VP) versus norepinephrine (NE) on troponin, CK, and ECGs.

          Methods

          This was a prospective substudy of a randomized trial. Adults with septic shock randomly received, blinded, a low-dose infusion of VP (0.01 to 0.03 U/min) or NE (5 to 15 μg/min) in addition to open-label vasopressors, titrated to maintain a mean blood pressure of 65 to 75 mm Hg. Troponin I/T, CK, and CK-MB were measured, and 12-lead ECGs were recorded before study drug, and 6 hours, 2 days, and 4 days after study-drug initiation. Two physician readers, blinded to patient data and drug, independently interpreted ECGs.

          Results

          We enrolled 121 patients (median age, 63.9 years (interquartile range (IQR), 51.1 to 75.3), mean APACHE II 28.6 (SD 7.7)): 65 in the VP group and 56 in the NE group. At the four time points, 26%, 36%, 32%, and 21% of patients had troponin elevations, respectively. Baseline characteristics and outcomes were similar between patients with positive versus negative troponin levels. Troponin and CK levels and rates of ischemic ECG changes were similar in the VP and the NE groups. In multivariable analysis, only APACHE II was associated with 28-day mortality (OR, 1.07; 95% CI, 1.01 to 1.14; P = 0.033).

          Conclusions

          Troponin elevation is common in adults with septic shock. We observed no significant differences in troponin, CK, and ECGs in patients treated with vasopressin and norepinephrine. Troponin elevation was not an independent predictor of mortality.

          Trial registration

          Controlled-trials.com ISRCTN94845869

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          Most cited references27

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          Troponin as a risk factor for mortality in critically ill patients without acute coronary syndromes.

          We sought to assess the mechanism and prognostic value of elevated troponins in patients without acute coronary syndromes (ACS). Cardiac troponins are used as specific markers for the diagnosis of ACS. Recent studies reported a considerable number of critically ill patients without ACS as being troponin-positive, especially patients with sepsis, pulmonary embolism, renal failure, and stroke. We analyzed 58 consecutive, critically ill patients admitted for reasons other than ACS, according to their troponin status. Thirty-day mortality, left ventricular ejection fraction (LVEF), and a panel of inflammatory cytokines were compared between troponin-positive and troponin-negative patients. Relevant coronary artery disease was excluded either by stress echocardiography or autopsy. Of the 58 critically ill patients, 32 (55%) without evidence of ACS were troponin-positive. Positive troponin levels were associated with higher mortality (22.4% vs. 5.2%, p < 0.018) and a lower LVEF (p = 0.0006). Troponin-positive patients had significantly higher median levels of tumor necrosis factor (TNF)-alpha, its soluble receptor, and interleukin (IL)-6. A subgroup of 10 aplastic patients was troponin-negative at study entry. Three became troponin-positive during leukocyte recovery and subsequently died, whereas all the others stayed troponin-negative and survived. Flow-limiting coronary artery disease was not demonstrable at autopsy or stress echocardiography in 72% of troponin-positive patients. Elevated troponin is a mortality risk factor for medical intensive care patients admitted for reasons other than ACS. It is associated with decreased left ventricular function and higher levels of TNF-alpha and IL-6.
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            Vasoactive drugs in circulatory shock.

            Shock occurs when failure of the cardiovascular system compromises tissue perfusion. When fluid administration fails to restore adequate arterial pressure and organ perfusion in patients with shock, therapy with vasoactive agents should be initiated. The key to selecting among vasoactive agents is to make the choice in the context of the goals of therapy. The ultimate goals of hemodynamic therapy in shock are to restore effective tissue perfusion and to normalize cellular metabolism. The clinician needs to consider ways of achieving those goals and the mechanisms of action of potential therapies. Armed with this knowledge, it becomes easier to match the mechanism of action of a particular agent to the goals of therapy. When this is done, differences among various agents are seen primarily as differences in mechanisms of action, and discussions about which agent is "best" are transformed into consideration of which agent is best suited to implement the therapeutic strategy that has been selected in a given clinical context. Despite the complex pathophysiology of shock, use of vasoactive agents for hemodynamic support of patients with shock can be guided by an underlying approach in which clinicians define specific goals and end points, titrate therapies to those end points, and evaluate the results of their interventions on an ongoing basis.
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              Elevated cardiac troponin measurements in critically ill patients.

              The clinical significance of elevated cardiac troponin (cTn) level in patients in the intensive care unit (ICU) is uncertain. We reviewed the frequency of cTn elevation and its association with mortality and length of ICU stay in these patients. Studies were identified using MEDLINE, EMBASE, and reference list review. We included observational studies of critically ill patients that measured cTn at least once and reported the frequency of elevated cTn or outcome (mortality and length of ICU or hospital stay). We pooled the odds ratios (ORs) using the inverse variance method in studies that conducted multivariable analysis to examine the relationship between elevated cTn and mortality (adjusted analysis). We calculated the weighted mean difference in length of stay between patients with and without elevated cTn and pooled the results using the inverse variance method (unadjusted analysis). A total of 23 studies involving 4492 critically ill patients were included. In 20 studies, elevated cTn was found in a median of 43% (interquartile range, 21% to 59%) of 3278 patients. In adjusted analysis (6 studies comprising 1706 patients), elevated cTn was associated with an increased risk of death (OR, 2.5; 95% confidence interval [CI], 1.9 to 3.4; P < .001). In the unadjusted analysis (8 studies comprising 1019 patients), elevated cTn was associated with an increased length of ICU stay of 3.0 days (95% CI, 1.0 to 5.1 days; P = .004) and an increased length of hospital stay of 2.2 days (95% CI, -0.6 to 4.9; P = .12). Elevated cTn measurements among critically ill patients are associated with increased mortality and ICU length of stay. Research is needed to clarify the underlying causes of elevated cTn in this population and to examine their clinical significance.
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                Author and article information

                Contributors
                Journal
                Crit Care
                Crit Care
                Critical Care
                BioMed Central
                1364-8535
                1466-609X
                2013
                20 June 2013
                : 17
                : 3
                : R117
                Affiliations
                [1 ]Department of Medicine and Interdepartmental Division of Critical Care Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
                [2 ]University Health Network-General Division, University of Toronto, Toronto, Ontario, Canada
                [3 ]Intensive Care, Charing Cross Hospital, Imperial College, London, UK
                [4 ]Departments of Medicine, Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada
                [5 ]Department of Medicine and Division of Cardiology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
                [6 ]Department of Respiratory Medicine, Changi General Hospital, Singapore
                [7 ]School of Population and Public Health, Centre for Health Evaluation and Outcome Sciences, and University of British Columbia, Vancouver, British Columbia, Canada
                [8 ]Critical Care Research Laboratories, Heart and Lung Institute, St. Paul's Hospital, and University of British Columbia, Vancouver, British Columbia, Canada
                [9 ]Alfred Hospital, Monash University, Melbourne, Australia
                [10 ]Kelowna General Hospital, Kelowna, and University of British Columbia, Kelowna, British Columbia, Canada
                [11 ]Ottawa Hospital-General Campus, and University of Ottawa, Ottawa, Ontario, Canada
                [12 ]Mater Health Services, University of Queensland and Monash University, South Brisbane Queensland, Australia
                Author notes
                for the Vasopressin and Septic Shock Trial (VASST) Investigators
                Article
                cc12789
                10.1186/cc12789
                4057204
                23786655
                3c8f2936-02e5-46d0-b356-398f2fa41124
                Copyright © 2013 Mehta et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 December 2012
                : 4 March 2013
                : 20 June 2013
                Categories
                Research

                Emergency medicine & Trauma
                septic shock,myocardial ischemia,vasopressin,norepinephrine,troponin,electrocardiogram

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