Abstract:
OBJECTIVE:Our knowledge of the molecular mechanisms of sepsis has attained exponential growth. Yet, the pillars of its care remain antibiotics, fluid resuscitation, and physiologic support of failing organ systems. The inability to bring biologic breakthroughs to the bedside is not for lack of effort. Over 60 clinical trials of novel therapies, each heavily supported by the momentum of biologic data suggesting clinical utility, have been conducted and have failed to identify benefit. This mass of "negative" clinical data abut an equally towering mound of knowledge of sepsis biology, which collectively have led investigators to ask, "what happened?" DATA SOURCES:Review of published scientific literature via MEDLINE searches using key terms related to the article topics. STUDY SELECTION:Original articles, review articles, and systematic reviews were considered. DATA EXTRACTION:Articles were selected for inclusion based upon author consensus. DATA SYNTHESIS:Here, we present a synthetic review of some of the challenges in translating experimental animal models of sepsis to the bedside. We commence with the concept that the heterogeneity in the kinetics of the sepsis response serves as an important, often underappreciated but surmountable, source of translational impedance. Upon this groundwork, we discuss distinctions between animal experimentation and clinical trial design in the elements for hypothesis testing: cohort selection, power and sample size, randomization and blinding, and timing of intervention. From this concept, we develop a contextual framework for advancing the paradigm of animal-based investigations to facilitate science that transitions from molecule to medicine. CONCLUSIONS:A persistent divide exists between the laboratory and clinical research arenas, which may be addressable via systematic targeting of identified translational gaps.
journal_name
Crit Care Medjournal_title
Critical care medicineauthors
Lewis AJ,Lee JS,Rosengart MRdoi
10.1097/CCM.0000000000003271subject
Has Abstractpub_date
2018-09-01 00:00:00pages
1497-1505issue
9eissn
0090-3493issn
1530-0293pii
00003246-201809000-00017journal_volume
46pub_type
杂志文章,评审abstract::Oxygen availability during cardiopulmonary bypass was assessed in 22 patients under hypothermic and relatively normothermic conditions. The patients were divided into two groups, 17 of whom received ACD blood and 5, CPD blood. The mean P50 for all patients fell from a preoperative value of 25.9 +/- 2.4 (SD) to 15.6 +/...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-197705000-00007
更新日期:1977-05-01 00:00:00
abstract:OBJECTIVES:To determine whether contemporary β-lactam anti-infective dosing recommendations in critically ill children achieve concentrations associated with maximal anti-infective activity. The secondary objective was to describe the microbiological and clinical outcomes associated with β-lactam therapeutic drug manag...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000002817
更新日期:2018-02-01 00:00:00
abstract:OBJECTIVES:ICU admission delays can negatively affect patient outcomes, but emergency department volume and boarding times may also affect these decisions and associated patient outcomes. We sought to investigate the effect of emergency department and ICU capacity strain on ICU admission decisions and to examine the ef...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000002993
更新日期:2018-05-01 00:00:00
abstract::A closed system device with teflon needle, sideholes, and attached stopcock was designed and evaluated for diagnosis and evacuation of neonatal pneumothoraces. Experience with this device has demonstrated specific advantages over existing needles and techniques. Since the system is airtight, diagnosis of pneumothorax ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-197811000-00007
更新日期:1978-11-01 00:00:00
abstract:OBJECTIVE:To determine whether mechanical ventilation using high tidal volume is associated with nonpulmonary organ dysfunction that can be attenuated by dexamethasone. DESIGN:Prospective randomized animal intervention study. SETTING:Animal care facility in a university hospital. SUBJECTS:Sedated and tracheostomized...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.CCM.0000205663.92384.E7
更新日期:2006-04-01 00:00:00
abstract:OBJECTIVE:To evaluate the accuracies of the respiratory rate/tidal volume ratio (rate/volume ratio), minute volume, and negative inspired force in predicting weaning outcome in postoperative mechanically ventilated patients. DESIGN:A prospective, observational study. SETTING:Surgical intensive care unit of a 270-bed ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199702000-00010
更新日期:1997-02-01 00:00:00
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
doi:10.1097/00003246-199102000-00015
更新日期:1991-02-01 00:00:00
abstract:OBJECTIVE:To compare the effects of two different antibiotic regimes on the colonization and infection rates of critically ill pediatric patients. DESIGN:A prospective randomized trial. SETTING:A pediatric ICU in a university hospital. PATIENTS:Fifty critically ill pediatric patients who required intensive care for ...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00003246-199110000-00005
更新日期:1991-10-01 00:00:00
abstract::Severe complications sometimes occur in critically ill patients during intrahospital transport. Possible causes may be inadequate ventilation, insufficient monitoring, interrupted application of vasoactive drugs, or disconnections and accidental extubation. We constructed a transport unit equipped with a respirator; c...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199012000-00024
更新日期:1990-12-01 00:00:00
abstract:OBJECTIVE:To develop definitions of infection that can be used in clinical trials in patients with sepsis. CONTEXT:Infection is a key component of the definition of sepsis, yet there is currently no agreement on the definitions that should be used to identify specific infections in patients with sepsis. Agreeing on a ...
journal_title:Critical care medicine
pub_type: 共识发展会议,杂志文章,评审
doi:10.1097/01.ccm.0000168253.91200.83
更新日期:2005-07-01 00:00:00
abstract:OBJECTIVE:To review recent advances in the use of transforming growth factor (TGF)-beta in acute lung injury and to apply this knowledge to understanding the pathophysiology of this syndrome. DATA SOURCES AND STUDY SELECTION:Published research and review articles in the English language related to the role of TGF-beta...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/01.CCM.0000057901.92381.75
更新日期:2003-04-01 00:00:00
abstract::We describe the use of continuous negative extrathoracic pressure to treat successfully the adult respiratory distress syndrome in a 19-yr-old woman who resisted the application of positive airway pressure. Arterial hypoxemia was reversed with -26 cm H2O of extrathoracic pressure, produced by a modified Emerson iron l...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:
更新日期:1985-11-01 00:00:00
abstract::To determine whether end-tidal carbon dioxide tension (PETCO2) accurately reflects PaCO2 during high-frequency jet ventilation (HFJV), 43 studies were performed on eight mongrel dogs with normal lungs. During HFJV, minute volume was modified to obtain a range of PaCO2 values from 15.5 to 74.5 torr. When PETCO2 was mea...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198610000-00014
更新日期:1986-10-01 00:00:00
abstract:OBJECTIVE:To determine the blood discard volume, as a multiple of deadspace, that is required for accurate arterial blood gas and electrolyte testing from arterial catheters. DESIGN:Prospective, controlled, crossover trial. SETTING:Eighteen-bed intensive care unit of a metropolitan teaching hospital. PATIENTS:A tota...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1097/01.CCM.0000063448.98777.EF
更新日期:2003-06-01 00:00:00
abstract::The Simplified Acute Physiology Score (SAPS), the Acute Physiology and Chronic Health Evaluation II (APACHE II), the Acute Physiology Score (APS), and the Coronary Prognostic Index (CPI), calculated within the first 24 h of ICU admission, were compared in 76 patients with acute myocardial infarction (AMI). Sixteen (21...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198905000-00006
更新日期:1989-05-01 00:00:00
abstract::Critical decreases in oxygen delivery (DO2) and mixed venous oxygen saturation (SvO2) are associated with anaerobic metabolism and, therefore, lactic acidosis. We studied 50 consecutive patients with sepsis and 50 consecutive patients with acute myocardial infarction (AMI) in whom the arterial blood lactate was greate...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198807000-00001
更新日期:1988-07-01 00:00:00
abstract::The definition of sepsis has been recently modified to accommodate emerging knowledge in the field, while at the same time being recognized as challenging, if not impossible, to define. Here, we seek to clarify the current understanding of sepsis as one that has been typically framed as a disorder of inflammation to o...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000002172
更新日期:2017-02-01 00:00:00
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
doi:10.1097/CCM.0000000000001003
更新日期:2015-08-01 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 relationship between sublingual and intestinal mucosal microcirculatory perfusion. DESIGN:Observational, experimental study. SETTING:University-affiliated large animal laboratory. SUBJECTS:Ten fasted, anesthetized, mechanically ventilated, male pigs randomized to a sham group (n = 3) or to...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3181b029c1
更新日期:2009-11-01 00:00:00
abstract:OBJECTIVES:Pneumothorax is a frequent complication during mechanical ventilation. Electrical impedance tomography (EIT) is a noninvasive tool that allows real-time imaging of regional ventilation. The purpose of this study was to 1) identify characteristic changes in the EIT signals associated with pneumothoraces; 2) d...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e31816a0380
更新日期:2008-04-01 00:00:00
abstract:OBJECTIVE:To describe critical illnesses that occur commonly in patients with human immunodeficiency virus (HIV) infection. METHODS:We reviewed and summarized the literature on critical illness in HIV infection using a computerized MEDLINE search. SUMMARY:In the last 10 yrs, our perception of HIV infection and acquir...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/01.CCM.0000232491.15369.AB
更新日期:2006-09-01 00:00:00
abstract:OBJECTIVES:Previous workers have demonstrated that controlled mechanical ventilation results in diaphragm inactivity and elicits a rapid development of diaphragm weakness as a result of both contractile dysfunction and fiber atrophy. Limited data exist regarding the impact of pressure support ventilation, a commonly us...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e31823c8cc9
更新日期:2012-04-01 00:00:00
abstract::Amikacin was introduced as the primary aminoglycoside in our hospital to prevent the further development of multiply resistant Gram-negative organisms. This study compares clinical and microbiological data before and after institution of this policy to evaluate the influence on clinical outcome in patients as well as ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199006000-00005
更新日期:1990-06-01 00:00:00
abstract:OBJECTIVE:To evaluate the relationship between the acute inflammatory response after surgical trauma and changes in hepatic cytochrome P450 3A4 activity, compare changes in cytochrome P450 3A4 activity after procedures with varying degrees of surgical stress, and to explore the time course of any potential drug-cytokin...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.CCM.0000063040.24541.49
更新日期:2003-05-01 00:00:00
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
doi:10.1097/CCM.0b013e3181a03063
更新日期:2009-07-01 00:00:00
abstract::Because an acute coronary thrombotic event may be viewed as the main trigger of sudden cardiac arrest, urgent coronary angiography followed by percutaneous coronary intervention appeared as a promising tool in the early postresuscitation phase. Unfortunately, large randomized trials, which have unequivocally demonstra...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/ccm.0b013e31818a8ae6
更新日期:2008-11-01 00:00:00
abstract::Recorded values (SpO2) of oxygen saturation from six noninvasive pulse oximeters were compared to each other and to the value from a cooximeter. Simultaneous measurements were obtained from each instrument in eight healthy nonsmoking volunteers rendered hypoxic greater than 70% SpO2. Functional arterial oxygen saturat...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198907000-00016
更新日期:1989-07-01 00:00:00
abstract:OBJECTIVE:To evaluate the frequency and clinical correlates of ultrafilterable hypomagnesemia in neonates admitted to the neonatal intensive care unit (ICU). DESIGN:Prospective, observational study. SETTING:Massachusetts General Hospital and Mount Auburn Hospital. PATIENTS:A total of 117 patients (84 neonatal ICU pa...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199405000-00017
更新日期:1994-05-01 00:00:00
abstract:OBJECTIVE:When a patient is incompetent, the family is often considered to be a natural surrogate. The doctors' responsiveness to family wishes may vary. We explored if doctors' personal characteristics were associated with responsiveness to the relatives' wishes when admission to the intensive care unit (ICU) is consi...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3181958409
更新日期:2009-02-01 00:00:00