Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials.

doi:10.1097/CCM.0B013E3182A16898

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Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials.

Journal Article•DOI•

Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials.

Gilles L. Fraser¹, John W. Devlin, Craig P. Worby, Waleed Alhazzani, Juliana Barr, Joseph F. Dasta, John P. Kress, Judy E. Davidson, Frederick A Spencer - Show less +5 more•Institutions (1)

Tufts University¹

01 Sep 2013-Critical Care Medicine (Crit Care Med)-Vol. 41, Iss: 9

TL;DR: Current controlled data suggest that use of a dexmedetomidine- or propofol-based sedation regimen rather than a benzodiazepine- based sedative regimen in critically ill adults may reduce ICU length of stay and duration of mechanical ventilation.

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Abstract: Background:Use of dexmedetomidine or propofol rather than a benzodiazepine sedation strategy may improve ICU outcomes. We reviewed randomized trials comparing a benzodiazepine and nonbenzodiazepine regimen in mechanically ventilated adult ICU patients to determine if differences exist between these

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Journal Article•DOI•

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

[...]

Andrew Rhodes¹, Laura Evans², Waleed Alhazzani³, Mitchell M. Levy⁴, Massimo Antonelli⁵, Ricard Ferrer⁶, Anand Kumar⁷, Jonathan E. Sevransky⁸, Charles L. Sprung⁹, Mark E. Nunnally², Bram Rochwerg³, Gordon D. Rubenfeld¹⁰, Derek C. Angus¹¹, Djillali Annane, Richard Beale¹², Geoffrey J. Bellinghan¹³, Gordon R. Bernard¹⁴, Jean Daniel Chiche, Craig M. Coopersmith⁸, Daniel De Backer, Craig French, Seitaro Fujishima¹⁵, Herwig Gerlach, Jorge Hidalgo¹⁶, Steven M. Hollenberg¹⁷, Alan E. Jones¹⁸, Dilip R. Karnad, Ruth M. Kleinpell¹⁹, Younsuck Koh²⁰, Thiago Lisboa, Flávia Ribeiro Machado²¹, John J. Marini²², John C. Marshall²³, John E. Mazuski²⁴, Lauralyn McIntyre²⁵, Anthony S. McLean²⁶, Sangeeta Mehta²⁷, Rui Moreno, John Myburgh²⁸, Paolo Navalesi, Osamu Nishida²⁹, Tiffany M. Osborn²⁴, Anders Perner, Colleen M. Plunkett¹⁹, Marco Ranieri, Christa A. Schorr¹⁷, Maureen A. Seckel³⁰, Christopher W. Seymour¹¹, Lisa Shieh³¹, Khalid A. Shukri³², Steven Q. Simpson³³, Mervyn Singer, B. Taylor Thompson³⁴, Sean R. Townsend³⁵, Thomas Van der Poll³⁶, Jean Louis Vincent, W. Joost Wiersinga³⁶, Janice L. Zimmerman³⁷, R. Phillip Dellinger¹⁷ - Show less +55 more•Institutions (37)

St George's Hospital¹, New York University², McMaster University³, Brown University⁴, Catholic University of the Sacred Heart⁵, Hebron University⁶, University of Manitoba⁷, Emory University Hospital⁸, Hebrew University of Jerusalem⁹, Sunnybrook Health Sciences Centre¹⁰, University of Pittsburgh¹¹, Saint Thomas - West Hospital¹², University College London¹³, Vanderbilt University Medical Center¹⁴, Keio University¹⁵, Memorial Hospital of South Bend¹⁶, Cooper University Hospital¹⁷, University of Mississippi Medical Center¹⁸, Rush University Medical Center¹⁹, University of Ulsan²⁰, Federal University of São Paulo²¹, Regions Hospital²², St. Michael's Hospital²³, Washington University in St. Louis²⁴, Ottawa Hospital²⁵, University of Sydney²⁶, Mount Sinai Hospital²⁷, University of New South Wales²⁸, Fujita Health University²⁹, Christiana Care Health System³⁰, Stanford University³¹, King Abdullah University of Science and Technology³², University of Kansas³³, Harvard University³⁴, California Pacific Medical Center³⁵, University of Amsterdam³⁶, Houston Methodist Hospital³⁷

18 Jan 2017-Intensive Care Medicine

TL;DR: Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

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Abstract: To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012”. A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

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4,303 citations

The Cochrane Collaboration's tool for assessing risk of bias in randomised trials

[...]

Cochrane Bias

01 Jan 2011

2,529 citations

Journal Article•DOI•

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

[...]

Andrew Rhodes¹, Laura Evans², Waleed Alhazzani³, Mitchell M. Levy⁴, Massimo Antonelli⁵, Ricard Ferrer⁶, Anand Kumar⁷, Jonathan E. Sevransky⁸, Charles L. Sprung⁹, Mark E. Nunnally², Bram Rochwerg³, Gordon D. Rubenfeld¹⁰, Derek C. Angus¹¹, Djillali Annane, Richard Beale¹², Geoffrey J. Bellinghan¹³, Gordon R. Bernard¹⁴, Jean Daniel Chiche, Craig M. Coopersmith⁸, Daniel De Backer, Craig French, Seitaro Fujishima¹⁵, Herwig Gerlach, Jorge Hidalgo¹⁶, Steven M. Hollenberg¹⁷, Alan E. Jones¹⁸, Dilip R. Karnad, Ruth M. Kleinpell¹⁹, Younsuck Koh²⁰, Thiago Lisboa²¹, Flávia Ribeiro Machado²², John J. Marini²³, John C. Marshall¹⁰, John E. Mazuski²⁴, Lauralyn McIntyre²⁵, Anthony S. McLean²⁶, Sangeeta Mehta¹⁰, Rui Moreno, John Myburgh²⁷, Paolo Navalesi, Osamu Nishida²⁸, Tiffany M. Osborn²⁴, Anders Perner²⁹, Colleen M. Plunkett¹⁹, Marco Ranieri³⁰, Christa A. Schorr¹⁷, Maureen A. Seckel³¹, Christopher W. Seymour¹¹, Lisa Shieh³², Khalid A. Shukri³³, Steven Q. Simpson³⁴, Mervyn Singer¹³, B. Taylor Thompson³⁵, Sean R. Townsend³⁶, Thomas Van der Poll³⁷, Jean Louis Vincent³⁸, W. Joost Wiersinga³⁹, Janice L. Zimmerman³⁹, R. Phillip Dellinger¹⁷ - Show less +55 more•Institutions (39)

St George’s University Hospitals NHS Foundation Trust¹, New York University², McMaster University³, Brown University⁴, Catholic University of the Sacred Heart⁵, Autonomous University of Barcelona⁶, University of Manitoba⁷, Emory University⁸, Hebrew University of Jerusalem⁹, University of Toronto¹⁰, University of Pittsburgh¹¹, St Thomas' Hospital¹², University College London¹³, Vanderbilt University¹⁴, Keio University¹⁵, Memorial Hospital of South Bend¹⁶, Rowan University¹⁷, University of Mississippi¹⁸, Rush University Medical Center¹⁹, University of Ulsan²⁰, Universidade Federal do Rio Grande do Sul²¹, Federal University of São Paulo²², Regions Hospital²³, Washington University in St. Louis²⁴, University of Ottawa²⁵, University of Sydney²⁶, University of New South Wales²⁷, Fujita Health University²⁸, University of Copenhagen²⁹, Sapienza University of Rome³⁰, Christiana Care Health System³¹, Stanford University³², King Abdullah University of Science and Technology³³, University of Kansas³⁴, Harvard University³⁵, California Pacific Medical Center³⁶, University of Amsterdam³⁷, Université libre de Bruxelles³⁸, Houston Methodist Hospital³⁹

01 Mar 2017-Critical Care Medicine

TL;DR: A consensus committee of 55 international experts representing 25 international organizations was assembled at key international meetings (forSurviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012 as discussed by the authors ).

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Abstract: Objective:To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.”Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for

...read moreread less

2,414 citations

Journal Article•DOI•

Outcome of delirium in critically ill patients: systematic review and meta-analysis

[...]

Jorge I. F. Salluh, Han Wang¹, Eric B. Schneider¹, Neeraja Nagaraja¹, Gayane Yenokyan², Abdulla A. Damluji³, Rodrigo B. Serafim⁴, Robert Stevens¹ - Show less +4 more•Institutions (4)

Johns Hopkins University School of Medicine¹, Johns Hopkins University², University of Miami³, Federal University of Rio de Janeiro⁴

03 Jun 2015-BMJ

TL;DR: Nearly a third of patients admitted to an intensive care unit develop delirium, and these patients are at increased risk of dying during admission, longer stays in hospital, and cognitive impairment after discharge.

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Abstract: Objectives To determine the relation between delirium in critically ill patients and their outcomes in the short term (in the intensive care unit and in hospital) and after discharge from hospital. Design Systematic review and meta-analysis of published studies. Data sources PubMed, Embase, CINAHL, Cochrane Library, and PsychINFO, with no language restrictions, up to 1 January 2015. Eligibility criteria for selection studies Reports were eligible for inclusion if they were prospective observational cohorts or clinical trials of adults in intensive care units who were assessed with a validated delirium screening or rating system, and if the association was measured between delirium and at least one of four clinical endpoints (death during admission, length of stay, duration of mechanical ventilation, and any outcome after hospital discharge). Studies were excluded if they primarily enrolled patients with a neurological disorder or patients admitted to intensive care after cardiac surgery or organ/tissue transplantation, or centered on sedation management or alcohol or substance withdrawal. Data were extracted on characteristics of studies, populations sampled, identification of delirium, and outcomes. Random effects models and meta-regression analyses were used to pool data from individual studies. Results Delirium was identified in 5280 of 16 595 (31.8%) critically ill patients reported in 42 studies. When compared with control patients without delirium, patients with delirium had significantly higher mortality during admission (risk ratio 2.19, 94% confidence interval 1.78 to 2.70; P Conclusions Nearly a third of patients admitted to an intensive care unit develop delirium, and these patients are at increased risk of dying during admission, longer stays in hospital, and cognitive impairment after discharge.

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664 citations

Journal Article•DOI•

Sepsis: pathophysiology and clinical management

[...]

Jeffrey E. Gotts¹, Michael A. Matthay¹•Institutions (1)

University of California, San Francisco¹

23 May 2016-BMJ

TL;DR: Outcomes in sepsis have greatly improved overall, probably because of an enhanced focus on early diagnosis and fluid resuscitation, the rapid delivery of effective antibiotics, and other improvements in supportive care for critically ill patients.

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Abstract: Sepsis, severe sepsis, and septic shock represent increasingly severe systemic inflammatory responses to infection. Sepsis is common in the aging population, and it disproportionately affects patients with cancer and underlying immunosuppression. In its most severe form, sepsis causes multiple organ dysfunction that can produce a state of chronic critical illness characterized by severe immune dysfunction and catabolism. Much has been learnt about the pathogenesis of sepsis at the molecular, cell, and intact organ level. Despite uncertainties in hemodynamic management and several treatments that have failed in clinical trials, investigational therapies increasingly target sepsis induced organ and immune dysfunction. Outcomes in sepsis have greatly improved overall, probably because of an enhanced focus on early diagnosis and fluid resuscitation, the rapid delivery of effective antibiotics, and other improvements in supportive care for critically ill patients. These improvements include lung protective ventilation, more judicious use of blood products, and strategies to reduce nosocomial infections.

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663 citations

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Journal Article•DOI•

Meta-Analysis in Clinical Trials*

[...]

Rebecca DerSimonian¹, Rebecca DerSimonian², Nan M. Laird¹, Nan M. Laird²•Institutions (2)

Yale University¹, Harvard University²

01 Sep 1986-Controlled Clinical Trials

TL;DR: This paper examines eight published reviews each reporting results from several related trials in order to evaluate the efficacy of a certain treatment for a specified medical condition and suggests a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.

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The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials

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Julian P T Higgins¹, Douglas G. Altman², Peter C Gøtzsche³, Peter Jüni⁴, David Moher⁵, Andrew D Oxman, Jelena Savović⁶, Kenneth F. Schulz⁷, Laura Weeks⁵, Jonathan A C Sterne⁶ - Show less +6 more•Institutions (7)

University of Cambridge¹, University of Oxford², University of Copenhagen³, University of Bern⁴, Ottawa Hospital Research Institute⁵, University of Bristol⁶, Research Triangle Park⁷

18 Oct 2011-BMJ

TL;DR: The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate.

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Abstract: Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate

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APACHE II: a severity of disease classification system.

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William A. Knaus, Elizabeth A. Draper, Douglas P. Wagner, Jack E. Zimmerman

01 Oct 1985-Critical Care Medicine

TL;DR: The form and validation results of APACHE II, a severity of disease classification system that uses a point score based upon initial values of 12 routine physiologic measurements, age, and previous health status, are presented.

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Abstract: This paper presents the form and validation results of APACHE II, a severity of disease classification system. APACHE II uses a point score based upon initial values of 12 routine physiologic measurements, age, and previous health status to provide a general measure of severity of disease. An increasing score (range 0 to 71) was closely correlated with the subsequent risk of hospital death for 5815 intensive care admissions from 13 hospitals. This relationship was also found for many common diseases. When APACHE II scores are combined with an accurate description of disease, they can prognostically stratify acutely ill patients and assist investigators comparing the success of new or differing forms of therapy. This scoring index can be used to evaluate the use of hospital resources and compare the efficacy of intensive care in different hospitals or over time.

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14,583 citations

Journal Article•DOI•

APACHE II-A Severity of Disease Classification System: Reply

[...]

William A. Knaus, Elizabeth A. Draper, Douglas P. Wagner, Jack E. Zimmerman

01 Aug 1986-Critical Care Medicine

TL;DR: The form and validation results of APACHE II, a severity of disease classification system, are presented, showing an increasing score was closely correlated with the subsequent risk of hospital death for 5815 intensive care admissions from 13 hospitals.

...read moreread less

Abstract: This paper presents the form and validation results of APACHE II, a severity of disease classification system. APACHE II uses a point score based upon initial values of 12 routine physiologic measurements, age, and previous health status to provide a general measure of severity of disease. An increasing score (range 0 to 71) was closely correlated with the subsequent risk of hospital death for 5815 intensive care admissions from 13 hospitals. This relationship was also found for many common diseases.When APACHE II scores are combined with an accurate description of disease, they can prognostically stratify acutely ill patients and assist investigators comparing the success of new or differing forms of therapy. This scoring index can be used to evaluate the use of hospital resources and compare the efficacy of intensive care in different hospitals or over time.

...read moreread less

5,266 citations

"Benzodiazepine versus nonbenzodiaze..." refers background in this paper

...On average, patients were older (mean age = 59 yr), severely ill (average Acute Physiology and Chronic Health Evaluation II score = 21), and mostly (75%) medical (28)....
[...]
...Characteristics of Randomized Studies Evaluating the Effect of Benzodiazepine Versus Nonbenzodiazepine-Based Sedation on Clinical Outcomes Trial (n) Trial Design Patient Population (Severity of Illness) Interventiona Method and Frequency of Sedation Assessment/Sedation Goal Daily Sedation Interruption Ventilator Weaning Protocol Used Daily Delirium Assessment Defined Outcome Data Available Carson et al (2) (132) Randomized open-label, multicenter Medical (22)b Lorazepam by intermittent bolus Ramsay every 2 hr Yes Yes No ICU LOS, ventilator days, hospital mortality Propofol Ramsay of 2–3 Jakob et al (27) (500)c Randomized double-blind, double-dummy multinational, multicenter Mixedd (45)e Midazolam RASS every 2 hr Yes Not stated Nof ICU LOS, ventilator days, 45-d mortality Dexmedetomidine RASS of 0 to –3 Pandharipande et al (4) (103) Randomized, double-blind, multicenter Mixedd (28)b Lorazepam RASS (frequency not stated) No No Yes with CAM-ICU ICU LOS, ventilator days, 28-d mortality, delirium Dexmedetomidine RASS target determined by team Riker et al (5) (366) Randomized, double-blind, multicenter Mixedd (19)b Midazolam RASS every 4 hr Yes Not stated Yes with CAM-ICU ICU LOS, ventilator days, delirium, 30-d mortality Dexmedetomidine RASS of –2 to +1 Ruokonen et al (6) (67) Randomized, double-blind, double-dummy, multicenter Mixedd (2.5)g Midazolam RASS (frequency not stated) Yes Not stated Yes, but no details provided ICU LOS Dexmedetomidine RASS target determined by team Weinbroum et al (3) (67) Randomized, unblinded Mixedd (17)b Midazolam Propofol Unique scoring system developed for study (frequency of assessment not provided) No No No ICU LOS Target light sedation LOS = length of stay, RASS = Richmond Agitation-Sedation Scale, CAM-ICU = Confusion Assessment Method for the ICU. aContinuous IV infusion unless otherwise stated. bAverage Acute Physiology and Chronic Health Evaluation II score across all study groups. cBased on intention to treat. dMixed = mixed medical/surgical population. eAverage Simplified Acute Physiology Score-2 across all study groups. fDelirium assessment with CAM-ICU 48 hr after sedation discontinuance. gMean organ failure....
[...]
...Trial (n) Trial Design Patient Population (Severity of Illness) Interventiona Method and Frequency of Sedation Assessment/Sedation Goal Daily Sedation Interruption Ventilator Weaning Protocol Used Daily Delirium Assessment Defined Outcome Data Available Carson et al (2) (132) Randomized open-label, multicenter Medical (22)b Lorazepam by intermittent bolus Ramsay every 2 hr Yes Yes No ICU LOS, ventilator days, hospital mortality Propofol Ramsay of 2–3 Jakob et al (27) (500)c Randomized double-blind, double-dummy multinational, multicenter Mixedd (45)e Midazolam RASS every 2 hr Yes Not stated Nof ICU LOS, ventilator days, 45-d mortality Dexmedetomidine RASS of 0 to –3 Pandharipande et al (4) (103) Randomized, double-blind, multicenter Mixedd (28)b Lorazepam RASS (frequency not stated) No No Yes with CAM-ICU ICU LOS, ventilator days, 28-d mortality, delirium Dexmedetomidine RASS target determined by team Riker et al (5) (366) Randomized, double-blind, multicenter Mixedd (19)b Midazolam RASS every 4 hr Yes Not stated Yes with CAM-ICU ICU LOS, ventilator days, delirium, 30-d mortality Dexmedetomidine RASS of –2 to +1 Ruokonen et al (6) (67) Randomized, double-blind, double-dummy, multicenter Mixedd (2.5)g Midazolam RASS (frequency not stated) Yes Not stated Yes, but no details provided ICU LOS Dexmedetomidine RASS target determined by team Weinbroum et al (3) (67) Randomized, unblinded Mixedd (17)b Midazolam Propofol Unique scoring system developed for study (frequency of assessment not provided) No No No ICU LOS Target light sedation LOS = length of stay, RASS = Richmond Agitation-Sedation Scale, CAM-ICU = Confusion Assessment Method for the ICU. aContinuous IV infusion unless otherwise stated. bAverage Acute Physiology and Chronic Health Evaluation II score across all study groups. cBased on intention to treat. dMixed = mixed medical/surgical population. eAverage Simplified Acute Physiology Score-2 across all study groups. fDelirium assessment with CAM-ICU 48 hr after sedation discontinuance. gMean organ failure....
[...]
...Pandharipande et al (4) (103) Randomized, double-blind, multicenter Mixedd (28)b Lorazepam RASS (frequency not stated) No No Yes with CAM-ICU ICU LOS, ventilator days, 28-d mortality, delirium Dexmedetomidine RASS target determined by team...
[...]

Journal Article•DOI•

Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit

[...]

Juliana Barr¹, Gilles L. Fraser², Kathleen Puntillo³, E. Wesley Ely⁴, Céline Gélinas⁵, Joseph F. Dasta⁶, Judy E. Davidson⁷, John W. Devlin⁸, John P. Kress⁹, Aaron M. Joffe¹⁰, Douglas B. Coursin¹¹, Daniel Herr¹², Avery Tung⁹, Bryce R.H. Robinson¹³, Dorrie K. Fontaine¹⁴, Michael A. E. Ramsay¹⁵, Richard R. Riker², Curtis N. Sessler¹⁶, Brenda T. Pun⁴, Yoanna Skrobik¹⁷, Roman Jaeschke¹⁸ - Show less +17 more•Institutions (18)

Stanford University¹, Maine Medical Center², University of California, San Francisco³, Veterans Health Administration⁴, McGill University⁵, University of Texas at Austin⁶, Scripps Health⁷, Northeastern University⁸, University of Chicago⁹, University of Washington¹⁰, University of Wisconsin-Madison¹¹, University of Maryland, Baltimore¹², University of Cincinnati¹³, University of Virginia¹⁴, Baylor University Medical Center¹⁵, Virginia Commonwealth University¹⁶, Université de Montréal¹⁷, McMaster University¹⁸

01 Jan 2013-Critical Care Medicine

TL;DR: These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients.

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Abstract: Objective:To revise the “Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult” published in Critical Care Medicine in 2002.Methods:The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task f

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3,005 citations