Editorials 11. Behazin N, Jones SB, Cohen RI, et al: Respiratory restriction and elevated pleural and esophageal pressures in morbid obesity. J Appl Physiol 2010; 108:212–218
13. Albert RK, Hubmayr RD: The prone position eliminates compression of the lungs by the heart. Am J Respir Crit Care Med 2000; 161:1660–1665
12. Pelosi P, Croci M, Calappi E, et al: Prone positioning improves pulmonary function in obese patients during general anesthesia. Anesth Analg 1996; 83:578–583
14. Ninane V, Leduc D, Kafi SA, et al: Detection of expiratory flow limitation by manual compression of the abdominal wall. Am J Respir Crit Care Med 2001; 163:1326–1330
Translating Knowledge into Practice in Critical Care Settings* Tara Lagu MD, MPH Center for Quality of Care Research; Division of General Internal Medicine Baystate Medical Center Springfield, MA; and Tufts University School of Medicine Boston, MA
associated with the greatest improvements in processes of care; however, most of the included studies were single center and of poor to moderate quality, which limited the authors’ ability to identify the best strategies for improving the use of evidence-based practices in the ICU. What does this comprehensive review of the literature tell us about the state of KT in critical care?
K
1. There has been a sea change in the last decade around the science of KT: If this systematic review were conducted a decade ago, there would have been almost no literature to review. The number of included studies shows that awareness of and attention to KT have increased dramatically in recent years. Of course, the preponderance of small studies and lack of consistent improvement in clinical outcomes also demonstrates that the field has much left to accomplish. 2. There are unclear boundaries between interventions and KT: The most important advances in critical care over the last decade have not been “magic bullets,” but have been complex interventions requiring changes to the organization and delivery of care: Pronovost et al demonstrated that combining a series of evidence-based interventions using a checklist could dramatically reduce CCABSI, and Rivers et al described a protocol for early goal-directed sepsis care (4–6). Although it would appear that these complex interventions are ripe for studies of KT, it may be difficult for subsequent investigators to determine where the intervention ends and the KT begins. A recent large study of CCABSI prevention by Pronovost et al (5) that reported improved long-term outcomes in Michigan ICUs, for example, may discourage other similar studies of implementation of the protocol. 3. Processes are as important as clinical outcomes, but that may not make us feel better: Because the goal of KT is to translate evidence into practice, there is no requirement that interventions be associated with clinical outcomes. Ideally, the clinical benefits of the interventions have been proven, and the goal is to ensure that evidence-based processes are being used in real-world settings. Still, for those engaged in quality improvement activities, it can be frustrating when process measures are achieved but clinical outcomes fail to improve.
nowledge translation (KT) is the process of taking research findings and implementing them in realworld settings. The KT cautionary tale of our time is the story of beta blockers following acute myocardial infarction (AMI) (1). Randomized trials in the early 1970s described the benefits of beta blockers in AMI, yet guidelines did not even begin to recommend beta blockers for AMI until the late 1980s. As late as 1999, the highest performing hospitals were only treating 64% of AMI patients with beta blockers (2). Only after the Centers for Medicare and Medicaid Services included beta blockers after AMI as a publicly reported quality metric did national rates of use reach more than 90%. This slow translation of knowledge resulted in many preventable deaths. In this issue of Critical Care Medicine, Sinuff et al (3) report on their systematic review of KT interventions for critically ill patients. After an exhaustive search, they identified 119 articles in nine clinical areas: ventilator-associated pneumonia, prevention of central catheter-associated bloodstream infections (CCABSI), sedation, ventilator weaning, antibiotic stewardship, nutrition, hand hygiene, glycemic control, and sepsis. In a meta-analysis, they saw an association between KT interventions and care processes but did not observe an association between any specific KT intervention (e.g., education, protocols, and audit and feedback) and clinical outcomes. Protocols with or without education were * See also p. 2627. Key Words: dissemination and implementation; knowledge translation; meta-analysis; systematic review Dr. Lagu has disclosed that she does not have any potential conflicts of interest. Copyright © 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0b013e31829e4cab
Critical Care Medicine
www.ccmjournal.org
2659
Editorials
4. What is missing may be most notable: acute respiratory distress syndrome (ARDS) network is a multimillion dollar National Institutes of Health-funded clinical network established to carry out multicenter clinical trials for ARDS. The network published two clinical trials describing that lung-protective ventilation strategies with lower tidal volumes and airway pressures were associated with a reduction in mortality rate (7, 8). This work was among the most important new evidence added to the critical care literature in the last 20 years, but studies have reported that ventilator management in patients with ARDS changed little after publication (9, 10)—indicating a KT need. Yet KT studies of low-tidal volume ventilation in ARDS were not among the most represented clinical topics in this review (3). 5. There is a clear need for more external funding of KT for critical care: The authors of the study note that most of the included studies were either unfunded or did not specify their funding mechanism. It is nearly impossible to conduct large, multicentered studies of KT in critical care without external funding, which may explain why many of the included interventions were single center and of poor or moderate quality. Prior work has detailed the lack of funding for critical care research relative to spending on critical care (11) and lack of funding for research that examines healthcare delivery (12). Only with increased funding earmarked for delivery of evidence-based critical care therapies will large, high-quality studies of KT in critical care be possible. 6. There is a shortage of new knowledge to translate: Over the last decade, a variety of critical care therapies have fallen out of favor. Intensive blood glucose control was once thought to reduce morbidity and mortality in critically ill patients, but subsequent work has shown no benefit of intensive glucose control and harm associated with hypoglycemia (13–15). Drotrecogin alfa was withdrawn from the market by the manufacturer after a large trial showed no benefit in patients with septic shock (16). The gaps left by these high-profile reversals in recommended care have not been filled by promising new therapies for the critically ill, which may further explain dearth of KT in critical care. Despite these limitations, barriers to KT in critical care settings can be overcome. One notable critical care KT success is the Surviving Sepsis Campaign (SSC). The SSC enrolled more than 25,000 patients at more than 200 sites across the United States and Europe and has reported large mortality reductions across sites (17). Although only certain elements of the bundle have been shown to improve outcomes (18), the observed mortality reductions suggest that either the combination of therapies is synergistic or systematic efforts to measure and improve care may themselves have beneficial effects on outcomes. Perhaps most importantly, less than 10 years passed between the first trial and wide-scale implementation,
2660
www.ccmjournal.org
indicating that KT interventions in critical care can hasten the translation of knowledge on a large scale and have the potential to improve outcomes at the population level.
REFERENCES
1. Antman EM, Lau J, Kupelnick B, et al: A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts. Treatments for myocardial infarction. JAMA 1992; 268:240–248 2. Chen J, Radford MJ, Wang Y, et al: Do “America’s Best Hospitals” perform better for acute myocardial infarction? N Engl J Med 1999; 340:286–292 3. Sinuff T, Muscedere J, Adhikari NKJ, et al; For the KRITICAL Working Group, the Canadian Critical Care Trials Group, and the Canadian Critical Care Society: Knowledge Translation Interventions for Critically Ill Patients: A Systematic Review. Crit Care Med 2013; 41:2627–2640 4. Pronovost P, Needham D, Berenholtz S, et al: An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 2006; 355:2725–2732 5. Pronovost PJ, Goeschel CA, Colantuoni E, et al: Sustaining reductions in catheter related bloodstream infections in Michigan intensive care units: Observational study. BMJ 2010; 340:c309 6. Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy Collaborative Group: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368–1377 7. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000; 342:1301–1308 8. Amato MB, Barbas CS, Medeiros DM, et al: Effect of a protectiveventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998; 338:347–354 9. Rubenfeld GD, Cooper C, Carter G, et al: Barriers to providing lungprotective ventilation to patients with acute lung injury. Crit Care Med 2004; 32:1289–1293 10. Weinert CR, Gross CR, Marinelli WA: Impact of randomized trial results on acute lung injury ventilator therapy in teaching hospitals. Am J Respir Crit Care Med 2003; 167:1304–1309 11. Coopersmith CM, Wunsch H, Fink MP, et al: A comparison of critical care research funding and the financial burden of critical illness in the United States. Crit Care Med 2012; 40:1072–1079 12. Pronovost PJ, Goeschel CA: Time to take health delivery research seriously. JAMA 2011; 306:310–311 13. Finfer S, Chittock DR, Su SY, et al; The NICE-SUGAR Study Investigators: Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360:1283–1297 14. van den Berghe G, Wouters P, Weekers F, et al: Intensive insulin therapy in critically ill patients. N Engl J Med 2001; 345:1359–1367 15. Finfer S, Liu B, Chittock DR, et al: Hypoglycemia and risk of death in critically ill patients. N Engl J Med 2012; 367:1108–1118 16. Ranieri VM, Thompson BT, Barie PS, et al; PROWESS-SHOCK Study Group: Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 2012; 366:2055–2064 17. Levy MM, Dellinger RP, Townsend SR, et al: The Surviving Sepsis Campaign: Results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med 2010; 36:222–231 18. Ferrer R, Artigas A, Suarez D, et al; Edusepsis Study Group: Effectiveness of treatments for severe sepsis: A prospective, multicenter, observational study. Am J Respir Crit Care Med 2009; 180:861–866
November 2013 • Volume 41 • Number 11
13. Albert RK, Hubmayr RD: The prone position eliminates compression of the lungs by the heart. Am J Respir Crit Care Med 2000; 161:1660–1665
12. Pelosi P, Croci M, Calappi E, et al: Prone positioning improves pulmonary function in obese patients during general anesthesia. Anesth Analg 1996; 83:578–583
14. Ninane V, Leduc D, Kafi SA, et al: Detection of expiratory flow limitation by manual compression of the abdominal wall. Am J Respir Crit Care Med 2001; 163:1326–1330
Translating Knowledge into Practice in Critical Care Settings* Tara Lagu MD, MPH Center for Quality of Care Research; Division of General Internal Medicine Baystate Medical Center Springfield, MA; and Tufts University School of Medicine Boston, MA
associated with the greatest improvements in processes of care; however, most of the included studies were single center and of poor to moderate quality, which limited the authors’ ability to identify the best strategies for improving the use of evidence-based practices in the ICU. What does this comprehensive review of the literature tell us about the state of KT in critical care?
K
1. There has been a sea change in the last decade around the science of KT: If this systematic review were conducted a decade ago, there would have been almost no literature to review. The number of included studies shows that awareness of and attention to KT have increased dramatically in recent years. Of course, the preponderance of small studies and lack of consistent improvement in clinical outcomes also demonstrates that the field has much left to accomplish. 2. There are unclear boundaries between interventions and KT: The most important advances in critical care over the last decade have not been “magic bullets,” but have been complex interventions requiring changes to the organization and delivery of care: Pronovost et al demonstrated that combining a series of evidence-based interventions using a checklist could dramatically reduce CCABSI, and Rivers et al described a protocol for early goal-directed sepsis care (4–6). Although it would appear that these complex interventions are ripe for studies of KT, it may be difficult for subsequent investigators to determine where the intervention ends and the KT begins. A recent large study of CCABSI prevention by Pronovost et al (5) that reported improved long-term outcomes in Michigan ICUs, for example, may discourage other similar studies of implementation of the protocol. 3. Processes are as important as clinical outcomes, but that may not make us feel better: Because the goal of KT is to translate evidence into practice, there is no requirement that interventions be associated with clinical outcomes. Ideally, the clinical benefits of the interventions have been proven, and the goal is to ensure that evidence-based processes are being used in real-world settings. Still, for those engaged in quality improvement activities, it can be frustrating when process measures are achieved but clinical outcomes fail to improve.
nowledge translation (KT) is the process of taking research findings and implementing them in realworld settings. The KT cautionary tale of our time is the story of beta blockers following acute myocardial infarction (AMI) (1). Randomized trials in the early 1970s described the benefits of beta blockers in AMI, yet guidelines did not even begin to recommend beta blockers for AMI until the late 1980s. As late as 1999, the highest performing hospitals were only treating 64% of AMI patients with beta blockers (2). Only after the Centers for Medicare and Medicaid Services included beta blockers after AMI as a publicly reported quality metric did national rates of use reach more than 90%. This slow translation of knowledge resulted in many preventable deaths. In this issue of Critical Care Medicine, Sinuff et al (3) report on their systematic review of KT interventions for critically ill patients. After an exhaustive search, they identified 119 articles in nine clinical areas: ventilator-associated pneumonia, prevention of central catheter-associated bloodstream infections (CCABSI), sedation, ventilator weaning, antibiotic stewardship, nutrition, hand hygiene, glycemic control, and sepsis. In a meta-analysis, they saw an association between KT interventions and care processes but did not observe an association between any specific KT intervention (e.g., education, protocols, and audit and feedback) and clinical outcomes. Protocols with or without education were * See also p. 2627. Key Words: dissemination and implementation; knowledge translation; meta-analysis; systematic review Dr. Lagu has disclosed that she does not have any potential conflicts of interest. Copyright © 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0b013e31829e4cab
Critical Care Medicine
www.ccmjournal.org
2659
Editorials
4. What is missing may be most notable: acute respiratory distress syndrome (ARDS) network is a multimillion dollar National Institutes of Health-funded clinical network established to carry out multicenter clinical trials for ARDS. The network published two clinical trials describing that lung-protective ventilation strategies with lower tidal volumes and airway pressures were associated with a reduction in mortality rate (7, 8). This work was among the most important new evidence added to the critical care literature in the last 20 years, but studies have reported that ventilator management in patients with ARDS changed little after publication (9, 10)—indicating a KT need. Yet KT studies of low-tidal volume ventilation in ARDS were not among the most represented clinical topics in this review (3). 5. There is a clear need for more external funding of KT for critical care: The authors of the study note that most of the included studies were either unfunded or did not specify their funding mechanism. It is nearly impossible to conduct large, multicentered studies of KT in critical care without external funding, which may explain why many of the included interventions were single center and of poor or moderate quality. Prior work has detailed the lack of funding for critical care research relative to spending on critical care (11) and lack of funding for research that examines healthcare delivery (12). Only with increased funding earmarked for delivery of evidence-based critical care therapies will large, high-quality studies of KT in critical care be possible. 6. There is a shortage of new knowledge to translate: Over the last decade, a variety of critical care therapies have fallen out of favor. Intensive blood glucose control was once thought to reduce morbidity and mortality in critically ill patients, but subsequent work has shown no benefit of intensive glucose control and harm associated with hypoglycemia (13–15). Drotrecogin alfa was withdrawn from the market by the manufacturer after a large trial showed no benefit in patients with septic shock (16). The gaps left by these high-profile reversals in recommended care have not been filled by promising new therapies for the critically ill, which may further explain dearth of KT in critical care. Despite these limitations, barriers to KT in critical care settings can be overcome. One notable critical care KT success is the Surviving Sepsis Campaign (SSC). The SSC enrolled more than 25,000 patients at more than 200 sites across the United States and Europe and has reported large mortality reductions across sites (17). Although only certain elements of the bundle have been shown to improve outcomes (18), the observed mortality reductions suggest that either the combination of therapies is synergistic or systematic efforts to measure and improve care may themselves have beneficial effects on outcomes. Perhaps most importantly, less than 10 years passed between the first trial and wide-scale implementation,
2660
www.ccmjournal.org
indicating that KT interventions in critical care can hasten the translation of knowledge on a large scale and have the potential to improve outcomes at the population level.
REFERENCES
1. Antman EM, Lau J, Kupelnick B, et al: A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts. Treatments for myocardial infarction. JAMA 1992; 268:240–248 2. Chen J, Radford MJ, Wang Y, et al: Do “America’s Best Hospitals” perform better for acute myocardial infarction? N Engl J Med 1999; 340:286–292 3. Sinuff T, Muscedere J, Adhikari NKJ, et al; For the KRITICAL Working Group, the Canadian Critical Care Trials Group, and the Canadian Critical Care Society: Knowledge Translation Interventions for Critically Ill Patients: A Systematic Review. Crit Care Med 2013; 41:2627–2640 4. Pronovost P, Needham D, Berenholtz S, et al: An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 2006; 355:2725–2732 5. Pronovost PJ, Goeschel CA, Colantuoni E, et al: Sustaining reductions in catheter related bloodstream infections in Michigan intensive care units: Observational study. BMJ 2010; 340:c309 6. Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy Collaborative Group: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368–1377 7. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000; 342:1301–1308 8. Amato MB, Barbas CS, Medeiros DM, et al: Effect of a protectiveventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998; 338:347–354 9. Rubenfeld GD, Cooper C, Carter G, et al: Barriers to providing lungprotective ventilation to patients with acute lung injury. Crit Care Med 2004; 32:1289–1293 10. Weinert CR, Gross CR, Marinelli WA: Impact of randomized trial results on acute lung injury ventilator therapy in teaching hospitals. Am J Respir Crit Care Med 2003; 167:1304–1309 11. Coopersmith CM, Wunsch H, Fink MP, et al: A comparison of critical care research funding and the financial burden of critical illness in the United States. Crit Care Med 2012; 40:1072–1079 12. Pronovost PJ, Goeschel CA: Time to take health delivery research seriously. JAMA 2011; 306:310–311 13. Finfer S, Chittock DR, Su SY, et al; The NICE-SUGAR Study Investigators: Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360:1283–1297 14. van den Berghe G, Wouters P, Weekers F, et al: Intensive insulin therapy in critically ill patients. N Engl J Med 2001; 345:1359–1367 15. Finfer S, Liu B, Chittock DR, et al: Hypoglycemia and risk of death in critically ill patients. N Engl J Med 2012; 367:1108–1118 16. Ranieri VM, Thompson BT, Barie PS, et al; PROWESS-SHOCK Study Group: Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 2012; 366:2055–2064 17. Levy MM, Dellinger RP, Townsend SR, et al: The Surviving Sepsis Campaign: Results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med 2010; 36:222–231 18. Ferrer R, Artigas A, Suarez D, et al; Edusepsis Study Group: Effectiveness of treatments for severe sepsis: A prospective, multicenter, observational study. Am J Respir Crit Care Med 2009; 180:861–866
November 2013 • Volume 41 • Number 11
