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      Fenoldopam use in a burn intensive care unit: a retrospective study

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          Abstract

          Background

          Fenoldopam mesylate is a highly selective dopamine-1 receptor agonist approved for the treatment of hypertensive emergencies that may have a role at low doses in preserving renal function in those at high risk for or with acute kidney injury (AKI). There is no data on low-dose fenoldopam in the burn population. The purpose of our study was to describe our use of low-dose fenoldopam (0.03-0.09 μg/kg/min) infusion in critically ill burn patients with AKI.

          Methods

          We performed a retrospective analysis of consecutive patients admitted to our burn intensive care unit (BICU) with severe burns from November 2005 through September 2008 who received low-dose fenoldopam. Data obtained included systolic blood pressure, serum creatinine, vasoactive medication use, urine output, and intravenous fluid. Patients on concomitant continuous renal replacement therapy were excluded. Modified inotrope score and vasopressor dependency index were calculated. One-way analysis of variance with repeated measures, Wilcoxson signed rank, and chi-square tests were used. Differences were deemed significant at p < 0.05.

          Results

          Seventy-seven patients were treated with low-dose fenoldopam out of 758 BICU admissions (10%). Twenty (26%) were AKI network (AKIN) stage 1, 14 (18%) were AKIN stage 2, 42 (55%) were AKIN stage 3, and 1 (1%) was AKIN stage 0. Serum creatinine improved over the first 24 hours and continued to improve through 48 hours ( p < 0.05). There was an increase in systolic blood pressure in the first 24 hours that was sustained through 48 hours after initiation of fenoldopam ( p < 0.05). Urine output increased after initiation of fenoldopam without an increase in intravenous fluid requirement ( p < 0.05; p = NS). Modified inotrope score and vasopressor dependency index both decreased over 48 hours ( p < 0.0001; p = 0.0012).

          Conclusions

          These findings suggest that renal function was preserved and that urine output improved without a decrease in systolic blood pressure, increase in vasoactive medication use, or an increase in resuscitation requirement in patients treated with low-dose fenoldopam. A randomized controlled trial is required to establish the efficacy of low-dose fenoldopam in critically ill burn patients with AKI.

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          Most cited references42

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          TLR4 activation mediates kidney ischemia/reperfusion injury.

          Ischemia/reperfusion injury (IRI) may activate innate immunity through the engagement of TLRs by endogenous ligands. TLR4 expressed within the kidney is a potential mediator of innate activation and inflammation. Using a mouse model of kidney IRI, we demonstrated a significant increase in TLR4 expression by tubular epithelial cells (TECs) and infiltrating leukocytes within the kidney following ischemia. TLR4 signaling through the MyD88-dependent pathway was required for the full development of kidney IRI, as both TLR4(-/-) and MyD88(-/-) mice were protected against kidney dysfunction, tubular damage, neutrophil and macrophage accumulation, and expression of proinflammatory cytokines and chemokines. In vitro, WT kidney TECs produced proinflammatory cytokines and chemokines and underwent apoptosis after ischemia. These effects were attenuated in TLR4(-/-) and MyD88(-/-) TECs. In addition, we demonstrated upregulation of the endogenous ligands high-mobility group box 1 (HMGB1), hyaluronan, and biglycan, providing circumstantial evidence that one or more of these ligands may be the source of TLR4 activation. To determine the relative contribution of TLR4 expression by parenchymal cells or leukocytes to kidney damage during IRI, we generated chimeric mice. TLR4(-/-) mice engrafted with WT hematopoietic cells had significantly lower serum creatinine and less tubular damage than WT mice reconstituted with TLR4(-/-) BM, suggesting that TLR4 signaling in intrinsic kidney cells plays the dominant role in mediating kidney damage.
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            Acute kidney injury in the intensive care unit according to RIFLE.

            To apply the RIFLE criteria "risk," "injury," and "failure" for severity of acute kidney injury to patients admitted to the intensive care unit and to evaluate the significance of other prognostic factors. Retrospective analysis of the Riyadh Intensive Care Program database. Riyadh Intensive Care Unit Program database of 41,972 patients admitted to 22 intensive care units in the United Kingdom and Germany between 1989 and 1999. Acute kidney injury as defined by the RIFLE classification occurred in 15,019 (35.8%) patients; 7,207 (17.2%) patients were at risk, 4,613 (11%) had injury, and 3,199 (7.6%) had failure. It was found that 797 (2.3%) patients had end-stage dialysis-dependent renal failure when admitted to an intensive care unit. None. : Patients with risk, injury, and failure classifications had hospital mortality rates of 20.9%, 45.6%, and 56.8%, respectively, compared with 8.4% among patients without acute kidney injury. Independent risk factors for hospital mortality were age (odds ratio 1.02); Acute Physiology and Chronic Health Evaluation II score on admission to intensive care unit (odds ratio 1.10); presence of preexisting end-stage disease (odds ratio 1.17); mechanical ventilation (odds ratio 1.52); RIFLE categories risk (odds ratio 1.40), injury (odds ratio 1.96), and failure (odds ratio 1.59); maximum number of failed organs (odds ratio 2.13); admission after emergency surgery (odds ratio 3.08); and nonsurgical admission (odds ratio 3.92). Renal replacement therapy for acute kidney injury was not an independent risk factor for hospital mortality. The RIFLE classification was suitable for the definition of acute kidney injury in intensive care units. There was an association between acute kidney injury and hospital outcome, but associated organ failure, nonsurgical admission, and admission after emergency surgery had a greater impact on prognosis than severity of acute kidney injury.
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              Long-term risk of mortality and acute kidney injury during hospitalization after major surgery.

              To determine the relationship between long-term mortality and acute kidney injury (AKI) during hospitalization after major surgery. AKI is associated with a risk of short-term mortality that is proportional to its severity; however the long-term survival of patients with AKI is poorly studied. This is a retrospective cohort study of 10,518 patients with no history of chronic kidney disease who were discharged after a major surgery between 1992 and 2002. AKI was defined by the RIFLE (Risk, Injury, Failure, Loss, and End-stage Kidney) classification, which requires at least a 50% increase in serum creatinine (sCr) and stratifies patients into 3 severity stages: risk, injury, and failure. Patient survival was determined through the National Social Security Death Index. Long-term survival was analyzed using a risk-adjusted Cox proportional hazards regression model. In the risk-adjusted model, survival was worse among patients with AKI and was proportional to its severity with an adjusted hazard ratio of 1.18 (95% confidence interval [CI], 1.08-1.29) for the RIFLE-Risk class and 1.57 (95% CI, 1.40-1.75) for the RIFLE-Failure class, compared with patients without AKI (P < 0.001). Patients with complete renal recovery after AKI still had an increased adjusted hazard ratio for death of 1.20 (95% CI, 1.10-1.31) compared with patients without AKI (P < 0.001). In a large single-center cohort of patients discharged after major surgery, AKI with even small changes in sCr level during hospitalization was associated with an independent long-term risk of death.
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                Author and article information

                Journal
                BMC Anesthesiol
                BMC Anesthesiology
                BioMed Central
                1471-2253
                2010
                24 June 2010
                : 10
                : 9
                Affiliations
                [1 ]United States Army Institute of Surgical Research, 3400 Rawley E. Chambers Avenue, Fort Sam Houston, Texas, 78234, USA
                [2 ]Wilford Hall Medical Center, 2200 Bergquist Drive, San Antonio, Texas, 78236, USA
                [3 ]UT Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, 78229, USA
                [4 ]Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland, 20814, USA
                Article
                1471-2253-10-9
                10.1186/1471-2253-10-9
                2904291
                20576149
                49767a2f-310c-45fd-bb10-04ca00ca6edb
                Copyright ©2010 Simmons 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
                : 27 February 2010
                : 24 June 2010
                Categories
                Research Article

                Anesthesiology & Pain management
                Anesthesiology & Pain management

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