Abstract:
OBJECTIVE:To review how endogenous protein C activation might change in disease states and to discuss the implications of these findings in the context of severe sepsis. DATA SOURCE:A review of the published literature in PubMed together with data from abstracts from 2001 to present. DATA EXTRACTION AND SYNTHESIS:Activated protein C (APC) supplementation has been shown to significantly reduce mortality in patients with severe sepsis, presumably by virtue of its ability to down-regulate coagulation, inflammation, and apoptosis. In vivo, endogenous APC is generated in the circulation when protein C is activated by the thrombin-thrombomodulin complex. Protein C activation is augmented by the endothelial cell protein C receptor. Thus, thrombomodulin and the endothelial cell protein C receptor are components of the endothelium-based "machinery" required for efficient activation of protein C. In healthy individuals, the amount of APC formed is proportional to thrombin levels. In vitro studies have shown that thrombomodulin and the endothelial cell protein C receptor are down-regulated by inflammatory cytokines, and the levels of these receptors are reduced in the endothelium of skin-biopsy specimens in children with severe meningococcal sepsis. However, endothelial studies of excised blood vessels provide only a partial picture of the APC pathway in vivo. Knowledge of endogenous plasma levels of protein C, thrombin, and APC may be helpful in assessing the functional status of the protein C pathway in the systemic circulation. To date, there are few reports available on endogenous APC levels in patients with severe sepsis, perhaps due to the lack of available assays that permit both rapid and accurate measurements. A unique feature of our study is that we have developed an APC assay that, for the first time, permits rapid and accurate measurements of plasma APC levels. Preliminary studies using this assay suggest that adult patients with severe sepsis vary markedly in their ability to generate APC endogenously. These results are intriguing because they suggest that, depending on individual defects in the protein C pathway, some patients have impaired protein C activation and might require APC therapy, whereas others may benefit from administration of protein C. Although the clinical efficacy of recombinant human APC (drotrecogin alfa [activated]) in severe sepsis has been reported in a phase III clinical trial, the efficacy of protein C in severe sepsis remains to be determined. CONCLUSIONS:Preliminary results suggest that adult patients with severe sepsis vary markedly in their ability to convert endogenous protein C to APC. Additional research is required to establish whether endogenous APC activation profiles are useful in the clinical management of patients with severe sepsis.
journal_name
Crit Care Medjournal_title
Critical care medicineauthors
Liaw PCdoi
10.1097/01.ccm.0000126125.79861.d3subject
Has Abstractpub_date
2004-05-01 00:00:00pages
S214-8issue
5 Suppleissn
0090-3493issn
1530-0293pii
00003246-200405001-00005journal_volume
32pub_type
杂志文章,评审abstract:OBJECTIVES:Extracellular mitochondrial DNA and N-formyl peptides released following tissue damage may contribute to systemic inflammation through stimulation of the innate immune system. In this review, we evaluate existing in vivo human data regarding a role for mitochondrial DNA and N-formyl peptides in producing sys...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000003381
更新日期:2018-12-01 00:00:00
abstract:OBJECTIVE:During cardiopulmonary bypass, inflammation and immunosuppression is present. We measured circulating mediators and monocyte-based functions and tested the hypothesis that these variables are influenced by methylprednisolone (MP) or tirilazad mesylate (TM) treatment. DESIGN:Randomized, controlled, double-bli...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00003246-200111000-00015
更新日期:2001-11-01 00:00:00
abstract:OBJECTIVE:This study tested the hypothesis that intra-coronary transfusion of circulation-derived autologous CD34+ cells can improve ischemia-related left ventricular dysfunction in patients with severe diffuse coronary artery disease refractory to medication and unsuitable for coronary intervention. DESIGN:A prospect...
journal_title:Critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1097/CCM.0000000000001138
更新日期:2015-10-01 00:00:00
abstract::Suction applied to a chest-tube drainage system produces subambient pressure within the chest tube and may increase or decrease the flow of gas passing from the airway through a bronchopleural fistula. Such gas may have participated in gas exchange and contain more CO2 and less O2 than inspired gas. Calculated or meas...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198502000-00009
更新日期:1985-02-01 00:00:00
abstract:OBJECTIVE:Physiologic and pathologic comparison of two modes of assisted ventilation, nasal intermittent positive-pressure ventilation (NIPPV) and synchronized intermittent mandatory ventilation (SIMV), in spontaneously breathing term newborn piglets with saline lavage-induced lung injury. DESIGN:After inducing acute ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.CCM.0000295311.61378.7D
更新日期:2008-01-01 00:00:00
abstract::The clearance of amikacin during hemodialysis (HD) was determined in eight critically ill patients. The dialysis period averaged 3.4 h with a blood flow of 200 ml/min. The average amikacin clearance between dialysis was 7.30 +/- 4.78 (SD) ml/min which increased to 37.5 +/- 8.01 ml/min during dialysis. The average seru...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198805000-00010
更新日期:1988-05-01 00:00:00
abstract:OBJECTIVES:To explore the relationship between timing of continuous renal replacement therapy commencement and clinical outcomes in critically ill patients with acute kidney injury. The primary outcomes were all-cause mortality at 28 and 90 days. DESIGN:Nested observational cohort study using data from the Randomized ...
journal_title:Critical care medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/CCM.0000000000000343
更新日期:2014-08-01 00:00:00
abstract:OBJECTIVE:Therapeutic hypothermia has been used to attenuate the effects of traumatic brain injuries. However, the required degree of hypothermia, length of its use, and its timing are uncertain. We undertook a comprehensive meta-analysis to quantify benefits of hypothermia therapy for traumatic brain injuries in adult...
journal_title:Critical care medicine
pub_type: 杂志文章,meta分析,评审
doi:10.1097/CCM.0000000000002205
更新日期:2017-04-01 00:00:00
abstract:OBJECTIVE:To describe the experience of pediatric intensive care hospitalization from the perspective of a parents of children with severe, antecedent disability. DESIGN:Qualitative analysis of data obtained through semistructured interviews. SETTING:Pediatric intensive care unit (PICU) in a children's hospital. SUB...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3181a00578
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND AND METHODS:A study was performed to examine the effects of the calcium-channel blocker levemopamil on neurologic outcome and neuropathology in a clinically relevant model of complete global cerebral ischemia (ventricular fibrillation in cats). Levemopamil was administered to cats starting 5 mins after resus...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199201000-00025
更新日期:1992-01-01 00:00:00
abstract:OBJECTIVE:To determine the role of serum albumin concentration as a predictor of mechanical ventilation dependency. DESIGN:Prospective, observation trial. SETTING:Multidisciplinary intensive care unit (ICU) in a university hospital. PATIENTS:One hundred forty-five consecutive patients who required mechanical ventila...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199604000-00009
更新日期:1996-04-01 00:00:00
abstract::Perfluorocarbon (PFC) emulsions are promising oxygen-carrying blood supplements for the treatment of shock and in organ preservation for transplantation. We used the isolated, blood-perfused, canine right lower lung lobe (RLL) to determine the effect of a PFC emulsion, Oxypherol (FC-43), upon lung fluid balance and he...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198512000-00006
更新日期:1985-12-01 00:00:00
abstract:OBJECTIVE:To test the hypothesis that the effects of intravenous injection of latex particles would demonstrate the contribution of phagocytosis by mononuclear phagocytes to the development of Escherichia coli-induced acute lung injury in neutropenic guinea pigs. DESIGN:Prospective, controlled, experimental study. Int...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199606000-00025
更新日期:1996-06-01 00:00:00
abstract:OBJECTIVE:The aim of the present study was to characterize pulmonary surfactant properties in children undergoing cardiovascular surgery with cardiopulmonary bypass. DESIGN:Prospective clinical trial. SETTING:University hospital pediatric intensive care unit. PATIENTS:Fifty pediatric patients with congenital cardiac...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1097/00003246-200301000-00045
更新日期:2003-01-01 00:00:00
abstract:OBJECTIVE:To describe a severe axonal polyneuropathy that follows acute respiratory failure and, in turn, causes continued ventilator dependence and paralysis after resolution of the primary illness. DESIGN:Retrospective chart review of three patients and prospective analysis of two patients. SETTING:Respiratory and ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199302000-00020
更新日期:1993-02-01 00:00:00
abstract:OBJECTIVE:This study determined the time course for inhibition of lipopolysaccharide-induced acute lung injury following a single dose of genistein. In addition, the study investigated whether a multiple dosing schedule with genistein retained the inhibitory effects on acute lung injury, nuclear factor-kappaB activatio...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.CCM.0000049941.84695.BA
更新日期:2003-02-01 00:00:00
abstract::The hospital records of 7 patients with severe bronchopulmonary dysplasia (BPD) were reviewed. All patients were ventilator dependent for prolonged periods (mean duration intermittent mandatory ventilation (IMV) 14.3 +/- 3.5 months) but eventually were successfully weaned from mechanical ventilation and sent home. The...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198112000-00001
更新日期:1981-12-01 00:00:00
abstract:OBJECTIVE:Quality of care for patients admitted with pneumonia varies across hospitals, but causes of this variation are poorly understood. Whether hospitals with high ICU utilization for patients with pneumonia provide better quality care is unknown. We sought to investigate the relationship between a hospital's ICU a...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000925
更新日期:2015-06-01 00:00:00
abstract:OBJECTIVES:Despite the universal proliferation of emergency medical services programs throughout the United States since 1970, only a few have ever documented a valid lifesaving effect, particularly in large, urban centers. The purpose of this study was to demonstrate the effect of specialized physician supervision on ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199309000-00009
更新日期:1993-09-01 00:00:00
abstract:OBJECTIVES:Acinetobacter baumannii complex bacteremia has been identified increasingly in critical patients admitted in ICUs. Notably, A. baumannii complex bacteremia has a high mortality rate, yet the risk factors associated with mortality remain unclear and controversial. DESIGN:Retrospective study. SETTING:All adu...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000125
更新日期:2014-05-01 00:00:00
abstract:OBJECTIVE:To determine whether polymorphisms of the surfactant protein B gene may be associated with increased mortality in patients with the acute respiratory distress syndrome. DESIGN:A prospective cohort study. SETTING:Four adult intensive care units at a tertiary academic medical center. PATIENTS:Two hundred fou...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e318183f608
更新日期:2008-09-01 00:00:00
abstract:OBJECTIVE:To examine the efficacy and safety of proton pump inhibitors in comparison with histamine-2 receptor antagonists for stress-related upper gastrointestinal bleeding prophylaxis among critical care patients. DATA SOURCES:PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov. STUDY SELECTION:Randomized, con...
journal_title:Critical care medicine
pub_type: 杂志文章,meta分析
doi:10.1097/CCM.0b013e3181d69ccf
更新日期:2010-04-01 00:00:00
abstract:OBJECTIVE:The clinical value of stroke volume variations to assess intravascular fluid status in critically ill patients is well known. Electrical impedance tomography is a noninvasive monitoring technology that has been primarily used to assess ventilation. We investigated the potential of electrical impedance tomogra...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3182227e65
更新日期:2011-09-01 00:00:00
abstract:OBJECTIVE:Acute-phase proteins, such as C-reactive protein and albumin, may be related with course and outcome in status epilepticus, as changes of cytokine levels and blood-brain barrier breakdown during status epilepticus have been demonstrated. The aim of this study was to elucidate the association of C-reactive pro...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e318287f2ac
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:Endotoxin (lipopolysaccharide [LPS]) has been associated with sepsis and the high mortality rate seen in septic shock. The administration of a small amount of LPS to healthy subjects produces a mild syndrome qualitatively similar to that seen in clinical sepsis. We used this model to test the efficacy of an ...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00003246-200008000-00005
更新日期:2000-08-01 00:00:00
abstract:OBJECTIVE:Recent studies have demonstrated the therapeutic effectiveness and pharmacologic mechanisms of hyperbaric oxygen therapy (HBOT) in the treatment of a systemic shock state. To elucidate the in vivo role of HBOT during sepsis, we evaluated the effects of HBOT on intestinal mucosal injury and bacterial transloca...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.ccm.0000132898.27101.6c
更新日期:2004-08-01 00:00:00
abstract:OBJECTIVES:Low tidal volume (= tidal volume ≤ 6 mL/kg, predicted body weight) ventilation using volume control benefits patients with acute respiratory distress syndrome. Airway pressure release ventilation is an alternative to low tidal volume-volume control ventilation, but the release breaths generated are variable ...
journal_title:Critical care medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/CCM.0000000000003437
更新日期:2018-12-01 00:00:00
abstract:BACKGROUND AND METHODS:We postulated that low-dose heparin (10 IU/kg.hr) administered as a continuous iv infusion may prevent or ameliorate the induction of thrombin-induced disseminated intravascular coagulation in baboons under general anesthesia. In a nonrandomized experiment lasting 8 hrs, animals were divided into...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199109000-00017
更新日期:1991-09-01 00:00:00
abstract:OBJECTIVE:To determine the limits of agreement between the cardiac output and volumetric data estimated by impedance cardiography with the cardiac output determined by thermodilution and the left ventricular ejection fraction and end-diastolic volume estimated from left ventriculography. DESIGN:A prospective study. S...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199709000-00023
更新日期:1997-09-01 00:00:00
abstract:OBJECTIVES:Lung CT is the reference imaging technique for acute respiratory distress syndrome, but requires transportation outside the intensive care and x-ray exposure. Lung ultrasound is a promising, inexpensive, radiation-free, tool for bedside imaging. Aim of the present study was to compare the global and regional...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000003971
更新日期:2019-11-01 00:00:00