Activated protein C in normal human pregnancy and pregnancies complicated by severe preeclampsia: a therapeutic opportunity?


OBJECTIVES:Given the efficacy and safety of recombinant human activated protein C (rhAPC) in the systemic inflammatory response syndrome, this study was designed to review the evidence for a role for APC in the pathogenesis of preeclampsia. Preeclampsia is a proinflammatory and procoagulant state, and it is a pregnancy-specific condition that mimics the systemic inflammatory response syndrome. rhAPC reduces mortality in patients with systemic inflammatory response syndrome and could potentially have a role as disease-modifying therapy in preeclampsia. To determine which patients would be offered rhAPC, the literature pertaining to fetal/neonatal outcomes for preeclampsia remote from term, transplacental transport of protein C, and pregnancy experience with the compound were reviewed. DATA SOURCES:MEDLINE, review papers, hand searches of relevant nonindexed journals, and the bibliographies of relevant textbooks and articles reviewed. STUDY SELECTION:Randomized controlled trials were considered to provide the best quality of clinical data. Case-control series were considered over uncontrolled data. Some data were not available in the published literature (e.g., neonatal outcomes at various gestational ages and birthweights after a hypertensive pregnancy; and transplacental transfer of protein C), and these data were determined by us. DATA EXTRACTION:Data were extracted by systematic review onto data collection sheets. Because of the quality of the data, this review is primarily qualitative. DATA SYNTHESIS:APC levels fall during normal gestation, returning to normal values by 6 wks postpartum. Limited data suggest that early onset preeclampsia is a state of further, and inappropriate, reduction in APC. Preeclampsia resembles systemic inflammatory response syndrome in this regard. After hypertensive pregnancies, neonates have a 50% chance of intact survival if delivered after 27 + 0 wks of gestation with a birthweight of >600 g. It would seem ethical to offer women with preeclampsia with <50% chance of intact perinatal survival novel and potentially disease-modifying therapy such as rhAPC, especially as there is no transplacental transfer of protein C. Limited evidence would support the use of rhAPC in women with severe postpartum preeclampsia. CONCLUSIONS:Sufficient data exist to support the use of rhAPC in phase II clinical studies for women with either early onset preeclampsia or severe or deteriorating postpartum disease.


Crit Care Med


Critical care medicine


von Dadelszen P,Magee LA,Lee SK,Stewart SD,Simone C,Koren G,Walley KR,Russell JA




Has Abstract


2002-08-01 00:00:00












  • Use of exogenous arginine in multiple organ dysfunction syndrome and sepsis.

    abstract::Given the multiple biological, metabolic, and pharmacologic effects of supplemental arginine, much effort has been devoted to defining its role in numerous clinical conditions. Herein, we review the multiple pathways of arginine metabolism with its various enzyme systems; the effect of arginine on nutrition, healing, ...

    journal_title:Critical care medicine

    pub_type: 杂志文章,评审


    authors: Barbul A,Uliyargoli A

    更新日期:2007-09-01 00:00:00

  • Association of hypomagnesemia and mortality in acutely ill medical patients.

    abstract:OBJECTIVE:To test the hypothesis that the mortality rate of acutely ill patients admitted to a medical ward or medical ICU is higher for those patients who present with hypomagnesemia than for those patients who do not present with hypomagnesemia. DESIGN:Prospective, observational study. SETTING:Emergency Department ...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Rubeiz GJ,Thill-Baharozian M,Hardie D,Carlson RW

    更新日期:1993-02-01 00:00:00

  • Written information that relatives of adult intensive care unit patients would like to receive--a comparison to published recommendations and opinion of staff members.

    abstract:OBJECTIVE:Information booklets have not been assessed by the families of intensive care unit (ICU) patients. This study explored the information that the relatives of adult ICU patients wanted to find in the information booklets. DESIGN:Multicenter survey. SETTING:Twenty-three French ICUs. SUBJECTS:One close relativ...

    journal_title:Critical care medicine

    pub_type: 杂志文章,多中心研究


    authors: Soltner C,Lassalle V,Galienne-Bouygues S,Pottecher J,Floccard B,Delapierre L,Jungfer F,Sargentini C,Alberti C,Beydon L,Lifrea Group.

    更新日期:2009-07-01 00:00:00

  • Multiple organ dysfunction syndrome: exploring the paradigm of complex nonlinear systems.

    abstract:OBJECTIVES:The objectives of this article are to introduce and explore a novel paradigm based on complex nonlinear systems, and to evaluate its application to critical care research regarding the systemic host response and multiple organ dysfunction syndrome (MODS). DATA SOURCES:Published original work, review article...

    journal_title:Critical care medicine

    pub_type: 杂志文章,评审


    authors: Seely AJ,Christou NV

    更新日期:2000-07-01 00:00:00

  • Increase in out-of-hospital cardiac arrest attended by the medical mobile intensive care units, but not myocardial infarction, during the 2003 heat wave in Paris, France.

    abstract:OBJECTIVES:To address the association between the 2003 heat wave in Paris (France) and the occurrence of out-of-hospital cardiac arrest. DESIGN:: An analysis of the interventions of the medical mobile intensive care units of the City of Paris for out-of-hospital cardiac arrest and prehospital myocardial infarctions, w...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Empana JP,Sauval P,Ducimetiere P,Tafflet M,Carli P,Jouven X

    更新日期:2009-12-01 00:00:00

  • Protective effect of N-acetylcysteine on multiple organ failure induced by zymosan in the rat.

    abstract:BACKGROUND AND METHODS:In the present study, we evaluated the effect of N-acetylcysteine treatment in a nonseptic shock model induced by zymosan in the rat. Animals were randomly divided into eight groups (ten animals in each group). The first group was treated with ip administration of saline solution (0.90% NaCl) and...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Cuzzocrea S,Costantino G,Mazzon E,Caputi AP

    更新日期:1999-08-01 00:00:00

  • Effect of combined nitric oxide inhalation and NG-nitro-L-arginine infusion in porcine endotoxin shock.

    abstract:OBJECTIVE:To evaluate the possible effects of a combination of systemic nitric oxide synthesis inhibition (to increase mean arterial blood pressure) and nitric oxide inhalation (to decrease pulmonary vascular pressure) in porcine endotoxin shock. DESIGN:Prospective trial. SETTING:Laboratory at a large university medi...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Weitzberg E,Rudehill A,Modin A,Lundberg JM

    更新日期:1995-05-01 00:00:00

  • Extracellular Mitochondrial DNA and N-Formyl Peptides in Trauma and Critical Illness: A Systematic Review.

    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


    authors: Lubkin DT,Bishawi M,Barbas AS,Brennan TV,Kirk AD

    更新日期:2018-12-01 00:00:00

  • Value and cost of teaching hospitals: a prospective, multicenter, inception cohort study.

    abstract:OBJECTIVE:To examine variations in case-mix, structure, resource use, and outcome performance among teaching and nonteaching intensive care units (ICU). DESIGN:Prospective inception cohort study. PATIENTS:A consecutive sample of 15,297 patients at 35 hospitals, which compared 8,269 patients admitted to 20 teaching IC...

    journal_title:Critical care medicine

    pub_type: 杂志文章,多中心研究


    authors: Zimmerman JE,Shortell SM,Knaus WA,Rousseau DM,Wagner DP,Gillies RR,Draper EA,Devers K

    更新日期:1993-10-01 00:00:00

  • Evaluation of the utility of computed tomography in the initial assessment of the critical care patient with chest trauma.

    abstract:OBJECTIVE:To determine the utility of thoracic computed tomography (TCT) in the initial assessment of critically ill patients with chest injuries. DESIGN:Prospective observational study of cohorts. SETTING:Trauma intensive care unit (ICU) of a Spanish Level III hospital (US equivalent Level I). PATIENTS:Three hundre...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Guerrero-López F,Vázquez-Mata G,Alcázar-Romero PP,Fernández-Mondéjar E,Aguayo-Hoyos E,Linde-Valverde CM

    更新日期:2000-05-01 00:00:00

  • Heparin-binding protein: a diagnostic marker of acute bacterial meningitis.

    abstract:BACKGROUND:The early detection of bacterial meningitis is crucial for successful outcome. Heparin-binding protein, a potent inducer of increased vascular permeability, is released from activated neutrophils in severe sepsis. OBJECTIVE:In this study we investigated whether heparin-binding protein levels in cerebrospina...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Linder A,Akesson P,Brink M,Studahl M,Björck L,Christensson B

    更新日期:2011-04-01 00:00:00

  • Endotoxemia reduces cerebral perfusion but enhances dynamic cerebrovascular autoregulation at reduced arterial carbon dioxide tension.

    abstract:OBJECTIVE:The administration of endotoxin to healthy humans reduces cerebral blood flow but its influence on dynamic cerebral autoregulation remains unknown. We considered that a reduction in arterial carbon dioxide tension would attenuate cerebral perfusion and improve dynamic cerebral autoregulation in healthy subjec...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Brassard P,Kim YS,van Lieshout J,Secher NH,Rosenmeier JB

    更新日期:2012-06-01 00:00:00

  • Prevalence of Thrombotic Complications in ICU-Treated Patients With Coronavirus Disease 2019 Detected With Systematic CT Scanning.

    abstract:OBJECTIVES:Severe coronavirus disease 2019 is associated with an extensive pneumonitis and frequent coagulopathy. We sought the true prevalence of thrombotic complications in critically ill patients with severe coronavirus disease 2019 on the ICU, with or without extracorporeal membrane oxygenation. DESIGN:We undertoo...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Mirsadraee S,Gorog DA,Mahon CF,Rawal B,Semple TR,Nicol ED,Arachchillage DRJ,Devaraj A,Price S,Desai SR,Ridge CA,Singh S,Padley SPG

    更新日期:2021-01-06 00:00:00

  • Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy for Acute Lymphoblastic Leukemia.

    abstract:OBJECTIVE:Initial success with chimeric antigen receptor-modified T cell therapy for relapsed/refractory acute lymphoblastic leukemia is leading to expanded use through multicenter trials. Cytokine release syndrome, the most severe toxicity, presents a novel critical illness syndrome with limited data regarding diagnos...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Fitzgerald JC,Weiss SL,Maude SL,Barrett DM,Lacey SF,Melenhorst JJ,Shaw P,Berg RA,June CH,Porter DL,Frey NV,Grupp SA,Teachey DT

    更新日期:2017-02-01 00:00:00

  • Osmotherapy with hypertonic saline attenuates water content in brain and extracerebral organs.

    abstract:OBJECTIVE:Because of their beneficial effects in patients with hemorrhagic shock and multiple-system trauma, hypertonic saline solutions are increasingly being used perioperatively for volume resuscitation. Although the anti-edema effects of hypertonic saline on brain are well documented in a variety of brain injury pa...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Toung TJ,Chen CH,Lin C,Bhardwaj A

    更新日期:2007-02-01 00:00:00

  • Characteristics and Outcomes of HIV-Infected Patients With Severe Sepsis: Continued Risk in the Post-Highly Active Antiretroviral Therapy Era.

    abstract:OBJECTIVES:Although highly active antiretroviral therapy has led to improved survival in HIV-infected individuals, outcomes for HIV-infected patients with sepsis in the post-highly active antiretroviral therapy era are conflicting. Access to highly active antiretroviral therapy and healthcare disparities continue to af...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Cribbs SK,Tse C,Andrews J,Shenvi N,Martin GS

    更新日期:2015-08-01 00:00:00

  • Long-term health-related quality of life in survivors of sepsis. Short Form 36: a valid and reliable measure of health-related quality of life.

    abstract:OBJECTIVE:To describe the long-term health-related quality of life (HRQL) of survivors of sepsis and to evaluate the reliability and validity of the medical outcomes study Short Form-36 (SF-36) in this population. STUDY DESIGN:Cross-sectional survey. SETTING:University intensive care unit. PATIENTS:Surviving patient...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Heyland DK,Hopman W,Coo H,Tranmer J,McColl MA

    更新日期:2000-11-01 00:00:00

  • Intensive care unit: how stressful for physicians?

    abstract::The ICU has been considered a psychologically stressful environment. Although numerous studies have investigated this stress in ICU nurses, virtually none have examined how stressful the ICU is for physicians. This prospective study compares housestaff physicians' ratings of stress in the ICU to other medical-surgical...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Eisendrath SJ,Link N,Matthay M

    更新日期:1986-02-01 00:00:00

  • Systemic and muscle oxygen uptake/delivery after dopexamine infusion in endotoxic dogs.

    abstract:BACKGROUND AND METHODS:This study was designed to test whether dopexamine, a dopaminergic and beta 2-adrenergic agonist, would a) increase systemic oxygen delivery (DO2) in endotoxic dogs, and b) interfere with the ability of resting skeletal muscle to extract oxygen. There were three treatment groups (n = 6 in each gr...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Bredle DL,Cain SM

    更新日期:1991-02-01 00:00:00

  • Corticosteroid Therapy Benefits Septic Mice With Adrenal Insufficiency But Harms Septic Mice Without Adrenal Insufficiency.

    abstract:OBJECTIVES:Corticosteroid therapy is frequently used in septic patients given the rationale that there is an increased demand for corticosteroid in sepsis, and up to 60% of severe septic patients experience adrenal insufficiency. However, the efficacy of corticosteroid therapy and whether the therapy should be based on...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Ai J,Guo L,Zheng Z,Wang SX,Huang B,Li XA

    更新日期:2015-11-01 00:00:00

  • Unmeasured anions in critically ill patients: can they predict mortality?

    abstract:OBJECTIVE:To determine whether base excess, base excess caused by unmeasured anions, and anion gap can predict lactate in adult critically ill patients, and also to determine whether acid-base variables can predict mortality in these patients. DESIGN:Retrospective study. SETTING:Adult intensive care unit of tertiary ...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Rocktaeschel J,Morimatsu H,Uchino S,Bellomo R

    更新日期:2003-08-01 00:00:00

  • Clinical utility of blood cultures drawn from central venous or arterial catheters in critically ill surgical patients.

    abstract:OBJECTIVE:To determine the sensitivity, specificity, and predictive values of cultures done with blood drawn through a central venous or arterial catheter compared with peripheral venipuncture. DESIGN:Retrospective cohort study of critically ill surgical patients in whom samples for paired cultures were drawn through ...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Martinez JA,DesJardin JA,Aronoff M,Supran S,Nasraway SA,Snydman DR

    更新日期:2002-01-01 00:00:00

  • Transbrachial insertion of a 7.5-Fr intra-aortic balloon pump in a severely atherosclerotic patient.

    abstract:OBJECTIVE:Preoperative intra-aortic balloon pumping (IABP) improves the results of complex coronary surgery. However, its insertion may be harmful or contraindicated in cases of severe and diffuse atherosclerosis of the descending aorta and peripheral arteries. We sought to evaluate the efficacy and safety of transbrac...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Onorati F,Bilotta M,Pezzo F,Impiombato B,Caroleo S,Santangelo E,Renzulli A

    更新日期:2006-08-01 00:00:00

  • Effects of pentoxifylline on circulating cytokine concentrations and hemodynamics in patients with septic shock: results from a double-blind, randomized, placebo-controlled study.

    abstract:OBJECTIVE:To determine whether a continuous intravenous infusion of pentoxifylline, a methylxanthine derivative, alters the serum cytokine concentrations and/or hemodynamic measurements in patients with septic shock. DESIGN:A prospective, randomized, double-blind, placebo-controlled study. SETTING:Medical intensive c...

    journal_title:Critical care medicine

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Zeni F,Pain P,Vindimian M,Gay JP,Gery P,Bertrand M,Page Y,Page D,Vermesch R,Bertrand JC

    更新日期:1996-02-01 00:00:00

  • Endotoxin increases plasma leptin and ghrelin levels in dogs.

    abstract:OBJECTIVE:Evaluations of plasma leptin and ghrelin levels and their relations with circulating levels of proinflammatory mediators, stress hormones, and biochemical markers of hepatorenal injury during experimental endotoxemia in dogs. SETTING:Uludag University. DESIGN:Placebo-controlled animal study. ANIMALS:Adult ...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Yilmaz Z,Ilcol YO,Ulus IH

    更新日期:2008-03-01 00:00:00

  • Predictors of noninvasive ventilation failure in patients with hematologic malignancy and acute respiratory failure.

    abstract:OBJECTIVES:The current trend to manage critically ill hematologic patients admitted with acute respiratory failure is to perform noninvasive ventilation to avoid endotracheal intubation. However, failure of noninvasive ventilation may lead to an increased mortality. DESIGN:Retrospective study to determine the frequenc...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Adda M,Coquet I,Darmon M,Thiery G,Schlemmer B,Azoulay E

    更新日期:2008-10-01 00:00:00

  • Epidemiology, management, and outcome of severe acute renal failure of critical illness in Australia.

    abstract:OBJECTIVE:To study the epidemiology, style of management, and outcome of intensive care patients with acute renal failure requiring replacement therapy in Australia. DESIGN:Prospective epidemiologic study. SETTING:Australian adult intensive care units providing acute renal replacement therapy. PATIENTS:Adult intensi...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Silvester W,Bellomo R,Cole L

    更新日期:2001-10-01 00:00:00

  • Reduced rate of bacterial translocation and improved variables of natural killer cell and T-cell activity in rats surviving controlled hemorrhagic shock and treated with hypertonic saline.

    abstract:OBJECTIVE:To examine the effect of hypertonic saline on bacterial translocation and the number and function of natural killer and T cells in controlled hemorrhagic shock. DESIGN:Randomized controlled study. Duration of follow-up was 24 hrs. SETTING:University research laboratory. SUBJECTS:Adult male Sprague-Dawley r...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Hirsh M,Dyugovskaya L,Bashenko Y,Krausz MM

    更新日期:2002-04-01 00:00:00

  • Comparison of multiple organ dysfunction scores in the prediction of hospital mortality in the critically ill.

    abstract:OBJECTIVE:To compare the scales and predictive power for hospital mortality of three recent multiple organ dysfunction scores. DESIGN:Prospective, observational, validation cohort study. SETTING:A ten-bed medical-surgical intensive care unit in a Finnish tertiary care hospital. PATIENTS:Among the 591 consecutive pat...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Pettilä V,Pettilä M,Sarna S,Voutilainen P,Takkunen O

    更新日期:2002-08-01 00:00:00

  • Impact of different customization strategies in the performance of a general severity score.

    abstract:OBJECTIVE:To compare the impact of two different customization strategies in the performance of the admission Mortality Probability Model II (MPM II0) using formal statistical assessment. DESIGN:Analysis of the database of a multicenter, multinational, prospective cohort study, EURICUS-1, involving 89 intensive care u...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Moreno R,Apolone G

    更新日期:1997-12-01 00:00:00