19
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Activated protein C in septic shock: a propensity-matched analysis

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction

          The use of human recombinant activated protein C (rhAPC) for the treatment of severe sepsis remains controversial despite multiple reported trials. The efficacy of rhAPC remains a matter of dispute. We hypothesized that patients with septic shock who were treated with rhAPC had an improved in-hospital mortality compared to patients with septic shock with similar acuity who did not receive rhAPC.

          Methods

          This retrospective cohort study was completed at a large university-affiliated hospital. All patients with septic shock admitted to a 50-bed ICU between July 2003 and February 2009 were included. Patients were treated according to sepsis management guidelines.

          Results

          A total of 563 septic shock patients were included (110 received rhAPC and 453 did not). Treated and untreated groups were matched in patient characteristics, comorbidities, and physiologic variables in a 1:1 propensity-matched analysis (108 received rhAPC, 108 did not). Mean Acute Physiology And Chronic Health Evaluation II (APACHE II) scores were 24.5 for the matched treated and 23.9 for the matched untreated group ( P = 0.54). Receipt of rhAPC was associated with reduced in-hospital mortality (35.2% vs. 53.8%, P = 0.005), similar mean days on vasopressors (2 vs. 2, P = 0.90), similar mean days on mechanical ventilation (9 vs. 8.7, P = 0.80), similar mean length of ICU stay in days (11.0 vs. 11.3, P = 0.90), and similar mean length of hospital stay in days (19.5 vs 27, P = 0.11). No patients in either group had intracranial bleeding; differences in gastrointestinal bleeding and transfusion requirements were not statistically significant.

          Conclusions

          Patients in our institution with septic shock who were treated with rhAPC had a reduced in-hospital mortality compared with patients with septic shock with similar acuity who were not treated with rhAPC. In addition, time on mechanical ventilation, time on vasopressors, lengths of stay and bleeding complications did not differ between the groups.

          Related collections

          Most cited references20

          • Record: found
          • Abstract: found
          • Article: not found

          Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis.

          To examine the incidence, risk factors, and outcome of severe sepsis in intensive care unit (ICU) patients. Inception cohort study from a 2-month prospective survey of 11,828 consecutive admissions to 170 adult ICUs of public hospitals in France. Patients meeting clinical criteria for severe sepsis were included and classified as having documented infection (ie, documented severe sepsis, n = 742), or a clinical diagnosis of infection without microbiological documentation (ie, culture-negative severe sepsis, n = 310). Hospital and 28-day mortality after severe sepsis. Clinically suspected sepsis and confirmed severe sepsis occurred in 9.0 (95% confidence interval [CI], 8.5 to 9.5) and 6.3 (95% CI, 5.8 to 6.7) of 100 ICU admissions, respectively. The 28-day mortality was 56% (95% CI, 52% to 60%) in patients with severe sepsis, and 60% (95% CI, 55% to 66%) in those with culture-negative severe sepsis. Major determinants of both early (< 3 days) and secondary deaths in the whole cohort were the Simplified Acute Physiology Score (SAPS) II and the number of acute organ system failures. Other risk factors for early death included a low arterial blood pH (< 7.33) (P < .001) and shock (P = .03), whereas secondary deaths were associated with the admission category (P < .001), a rapidly or ultimately fatal underlying disease (P < .001), a preexisting liver (P = .01) or cardiovascular (P = .002) insufficiency, hypothermia (P = .02), thrombocytopenia (P = .01), and multiple sources of infection (P = .02). In patients with documented sepsis, bacteremia was associated with early mortality (P = .03). Only three of four patients presenting with clinically suspected severe sepsis have documented infection. However, patients with clinically suspected sepsis but without microbiological documentation and patients with documented infection share common risk factors and are at similarly high risk of death. In addition to the severity of illness score, acute organ failures and the characteristics of underlying diseases should be accounted for in stratification of patients and outcome analyses.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Treating patients with severe sepsis.

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy.

              Septic shock is the commonest cause of death in intensive care units. Although sepsis usually produces a low systemic vascular resistance and elevated cardiac output, strong evidence (decreased ejection fraction and reduced response to fluid administration) suggests that the ventricular myocardium is depressed and the ventricle dilated. In survivors, these abnormalities are reversible. Failure to develop ventricular dilatation in nonsurvivors suggests that dilatation is a compensatory mechanism needed to maintain adequate cardiac output. With a canine model of septic shock that is very similar to human sepsis, myocardial depression was confirmed using load-independent measures of ventricular performance. Endotoxin administration to humans simulates the qualitative, cardiovascular abnormalities of sepsis. The pathogenesis of septic shock is extraordinarily complex. Diverse microorganisms can generate toxins, stimulating release of potent mediators that act on vasculature and myocardium. A circulating myocardial depressant substance has been closely associated with the myocardial depression of human septic shock. Therapy has emphasized early use of antibiotics, critical care monitoring, aggressive volume resuscitation, and, if shock continues, use of inotropic agents and vasopressors. Pharmacologic or immunologic antagonism of endotoxin or other mediators may prove to enhance survival in this highly lethal syndrome.
                Bookmark

                Author and article information

                Journal
                Crit Care
                Critical Care
                BioMed Central
                1364-8535
                1466-609X
                2011
                8 March 2011
                : 15
                : 2
                : R89
                Affiliations
                [1 ]St. John's Mercy Medical Center/St Louis University, 621 S New Ballas Rd., Suite 4006B, St. Louis, MO 63141, USA
                Article
                cc10089
                10.1186/cc10089
                3219349
                21385410
                de2418aa-abfa-4835-aacd-6a6967e1d898
                Copyright ©2011 Sadaka 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
                : 15 December 2010
                : 2 February 2011
                : 8 March 2011
                Categories
                Research

                Emergency medicine & Trauma
                Emergency medicine & Trauma

                Comments

                Comment on this article