A Look at Upcoming Surviving Sepsis 2012 Guidelines

DENVER – Look for some big changes ahead in the forthcoming update of the Surviving Sepsis Campaign international guidelines.

In the 4 years since the last version of the guidelines came out, major studies have been released that resolved hot debates regarding sepsis management and in some cases overturned established dogma. At the annual American College of Emergency Physicians (ACEP) meeting, emergency physicians deeply involved in crafting the Surviving Sepsis Campaign 2012 guidelines provided a preview of what’s to come.

Among the areas that will see key new recommendations are antibiotic therapy, fluid resuscitation, vasopressors, and lactate monitoring.

• Antibiotics ASAP. The critical importance of getting empiric antibiotics on board within 6 hours after recognizing that a patient has sepsis has been effectively hammered home over the years. But how fast is fast enough? Several recent small studies have reached conflicting conclusions. Now, however, an 800-lb gorilla of a study has provided a definitive answer.

This study, now in press, involved 14,895 patients enrolled in the Surviving Sepsis Campaign’s worldwide database. All had severe sepsis or septic shock, and all received antibiotics within the first 6 hours, explained Dr. Tiffany M. Osborn, a coauthor of the study and of the forthcoming guidelines.

"This was a big question for us. The results strengthen the importance of getting antibiotics started as soon as possible – within the first hour if possible. We found there’s about a 4% increase in mortality for every hour delay. And it’s cumulative: it’s 4% after the first hour, 8% after the second, 12% after the third, and so on," according to Dr. Osborn of Washington University at St. Louis.

A similar time-dependent increase in mortality was observed in patients with severe sepsis as well as in those in septic shock, she added.

• Fluid resuscitation. The initial fluid of choice for resuscitation in severe sepsis and septic shock remains crystalloids, as before. That’s a grade 1A recommendation. What’s brand new is a recommendation to consider adding albumin in the initial fluid resuscitation (grade 2B). This guidance was heavily influenced by a meta-analysis of 17 studies involving close to 2,000 patients that demonstrated a significant protective effect for the use of albumin as an initial resuscitation fluid (Crit. Care Med. 2011;39:386-91).

At this late date, Dr. Osborn said, the guideline panel is strongly leaning toward a recommendation against the use of low-molecular-weight colloids or starches such as hydroxyethyl starch 130/0.42. That would be ground shaking, as synthetic colloids or starches, particularly those of low molecular weight, are a very popular resuscitation fluid both in the United States and abroad. However, recent studies implicate these fluids in increased risks of 90-day mortality and renal failure, compared with the use of Ringer’s lactate.

"Having said this, there are two other trials currently pending. Any month now the results will come out, and we’ll see where we are at that point. But at this time, we’re thinking stay away from low-molecular-weight starches for resuscitation," Dr. Osborn said.

One of the main reasons the Surviving Sepsis Campaign 2012 guidelines won’t actually be published before January 2013 is the guideline panel’s eagerness to see the results of those two studies, she added.

• Vasopressor therapy. The initial target remains, as before, a mean arterial pressure of at least 65 mm Hg. But while the 2008 guidelines recommended either norepinephrine or dopamine as the first-choice vasopressor to correct hypotension in patients not sufficiently responsive to fluid resuscitation, the new guidelines will state that norepinephrine is the preferred agent (grade 1B). That’s a major change. Dopamine has been essentially kicked to the curb in response to multiple studies in the last 4 years implicating it in an increased incidence of arrhythmias and, in some studies, higher mortality.

The final nail in dopamine’s coffin for use in patients with severe sepsis or septic shock was a recent meta-analysis involving five observational and six interventional studies totaling nearly 2,800 patients (Crit. Care Med. 2012;40:725-30).

"Dopamine has actually fallen by the wayside. By far and away, I’m going to choose norepinephrine as the initial vasopressor agent," declared Dr. Michael E. Winters of the University of Maryland, Baltimore.

The new guidelines will suggest that be reserved for highly selected patients: those at very low arrhythmia risk and with a low cardiac output and/or low heart rate (grade 2C), he noted.

Another change in the new guidelines will be a recommendation that epinephrine be added when an additional agent is needed in order to maintain adequate blood pressure (grade 2B).

• Don’t overdo the fluids. "We want to give patients what they need but not more," Dr. Osborn explained. The 2012 guidelines will recommend that physicians use some sort of fluid challenge test while administering fluid boluses. The goal is to keep giving fluid only so long as hemodynamic improvement is seen in response. This can be achieved in a variety of ways, including monitoring change in pulse pressure, stroke volume variation, heart rate, or arterial pressure.

• Lactate clearance. Serum lactate is recognized as an indicator of global organ hypoperfusion and shock. But incorporating lactate clearance as one of the goals of early sepsis therapy has been "a very hot topic," Dr. Winters observed.

Improved clarity was provided by a prospective 556-patient quality improvement study by investigators in the Asian Network to Regulate Sepsis Care. Patients who got the primary severe sepsis management bundle of care as recommended in the 2008 Surviving Sepsis Campaign guidelines had an unadjusted mortality of 43.6%. This bundle includes early antibiotic administration, hemodynamic monitoring and support, and achievement of a central venous oxygen saturation level greater than 70% by 6 hours. However, patients who got the bundle plus lactate clearance had a 20.5% mortality rate (Crit. Care 2011;15:R229 [doi:10.1186/cc10469]).

The importance of lactate clearance was further underscored by the findings in the GENESIS Project (Generalized Early Sepsis Intervention Strategies). This quality improvement initiative, conducted at five 5 U.S. community hospitals and six tertiary centers, showed a 42.8% mortality in 1,554 historical controls treated for sepsis before implementation of the Surviving Sepsis Campaign resuscitation bundle. In another 4,801 patients who got the bundle, mortality was significantly lower at 28.8%. And, in those who received the bundle plus lactate clearance, mortality further fell to about 22% (J. Intensive Care Med. 2012 [doi:10.1177/0885066612453025]).

Thus, the coming Surviving Sepsis Campaign 2012 guidelines will suggest that in patients with elevated lactate levels as a marker of hypoperfusion, resuscitation should be targeted at normalizing lactate as rapidly as possible (grade 2C). Having said that, however, a normal lactate doesn’t indicate absence of shock. Other factors, such as the patient’s central venous oxygen saturation level, need to be considered as well, the physicians emphasized.

The Surviving Sepsis Campaign guidelines are sponsored by 27 medical organizations. Among them are the Society of Critical Care Medicine, ACEP, the Society of Hospital Medicine, the American College of Chest Physicians, the American Thoracic Society, the Infectious Diseases Society of America, the Surgical Infection Society, the Pediatric Acute Lung Injury and Sepsis Investigators, and a host of international groups.

Dr. Osborn and Dr. Winter reported having no financial conflicts.

DENVER – Look for some big changes ahead in the forthcoming update of the Surviving Sepsis Campaign international guidelines.

In the 4 years since the last version of the guidelines came out, major studies have been released that resolved hot debates regarding sepsis management and in some cases overturned established dogma. At the annual American College of Emergency Physicians (ACEP) meeting, emergency physicians deeply involved in crafting the Surviving Sepsis Campaign 2012 guidelines provided a preview of what’s to come.

Among the areas that will see key new recommendations are antibiotic therapy, fluid resuscitation, vasopressors, and lactate monitoring.

• Antibiotics ASAP. The critical importance of getting empiric antibiotics on board within 6 hours after recognizing that a patient has sepsis has been effectively hammered home over the years. But how fast is fast enough? Several recent small studies have reached conflicting conclusions. Now, however, an 800-lb gorilla of a study has provided a definitive answer.

This study, now in press, involved 14,895 patients enrolled in the Surviving Sepsis Campaign’s worldwide database. All had severe sepsis or septic shock, and all received antibiotics within the first 6 hours, explained Dr. Tiffany M. Osborn, a coauthor of the study and of the forthcoming guidelines.

"This was a big question for us. The results strengthen the importance of getting antibiotics started as soon as possible – within the first hour if possible. We found there’s about a 4% increase in mortality for every hour delay. And it’s cumulative: it’s 4% after the first hour, 8% after the second, 12% after the third, and so on," according to Dr. Osborn of Washington University at St. Louis.

A similar time-dependent increase in mortality was observed in patients with severe sepsis as well as in those in septic shock, she added.

• Fluid resuscitation. The initial fluid of choice for resuscitation in severe sepsis and septic shock remains crystalloids, as before. That’s a grade 1A recommendation. What’s brand new is a recommendation to consider adding albumin in the initial fluid resuscitation (grade 2B). This guidance was heavily influenced by a meta-analysis of 17 studies involving close to 2,000 patients that demonstrated a significant protective effect for the use of albumin as an initial resuscitation fluid (Crit. Care Med. 2011;39:386-91).

At this late date, Dr. Osborn said, the guideline panel is strongly leaning toward a recommendation against the use of low-molecular-weight colloids or starches such as hydroxyethyl starch 130/0.42. That would be ground shaking, as synthetic colloids or starches, particularly those of low molecular weight, are a very popular resuscitation fluid both in the United States and abroad. However, recent studies implicate these fluids in increased risks of 90-day mortality and renal failure, compared with the use of Ringer’s lactate.

"Having said this, there are two other trials currently pending. Any month now the results will come out, and we’ll see where we are at that point. But at this time, we’re thinking stay away from low-molecular-weight starches for resuscitation," Dr. Osborn said.

One of the main reasons the Surviving Sepsis Campaign 2012 guidelines won’t actually be published before January 2013 is the guideline panel’s eagerness to see the results of those two studies, she added.

• Vasopressor therapy. The initial target remains, as before, a mean arterial pressure of at least 65 mm Hg. But while the 2008 guidelines recommended either norepinephrine or dopamine as the first-choice vasopressor to correct hypotension in patients not sufficiently responsive to fluid resuscitation, the new guidelines will state that norepinephrine is the preferred agent (grade 1B). That’s a major change. Dopamine has been essentially kicked to the curb in response to multiple studies in the last 4 years implicating it in an increased incidence of arrhythmias and, in some studies, higher mortality.

The final nail in dopamine’s coffin for use in patients with severe sepsis or septic shock was a recent meta-analysis involving five observational and six interventional studies totaling nearly 2,800 patients (Crit. Care Med. 2012;40:725-30).

"Dopamine has actually fallen by the wayside. By far and away, I’m going to choose norepinephrine as the initial vasopressor agent," declared Dr. Michael E. Winters of the University of Maryland, Baltimore.

The new guidelines will suggest that be reserved for highly selected patients: those at very low arrhythmia risk and with a low cardiac output and/or low heart rate (grade 2C), he noted.

Another change in the new guidelines will be a recommendation that epinephrine be added when an additional agent is needed in order to maintain adequate blood pressure (grade 2B).

• Don’t overdo the fluids. "We want to give patients what they need but not more," Dr. Osborn explained. The 2012 guidelines will recommend that physicians use some sort of fluid challenge test while administering fluid boluses. The goal is to keep giving fluid only so long as hemodynamic improvement is seen in response. This can be achieved in a variety of ways, including monitoring change in pulse pressure, stroke volume variation, heart rate, or arterial pressure.

• Lactate clearance. Serum lactate is recognized as an indicator of global organ hypoperfusion and shock. But incorporating lactate clearance as one of the goals of early sepsis therapy has been "a very hot topic," Dr. Winters observed.

Improved clarity was provided by a prospective 556-patient quality improvement study by investigators in the Asian Network to Regulate Sepsis Care. Patients who got the primary severe sepsis management bundle of care as recommended in the 2008 Surviving Sepsis Campaign guidelines had an unadjusted mortality of 43.6%. This bundle includes early antibiotic administration, hemodynamic monitoring and support, and achievement of a central venous oxygen saturation level greater than 70% by 6 hours. However, patients who got the bundle plus lactate clearance had a 20.5% mortality rate (Crit. Care 2011;15:R229 [doi:10.1186/cc10469]).

The importance of lactate clearance was further underscored by the findings in the GENESIS Project (Generalized Early Sepsis Intervention Strategies). This quality improvement initiative, conducted at five 5 U.S. community hospitals and six tertiary centers, showed a 42.8% mortality in 1,554 historical controls treated for sepsis before implementation of the Surviving Sepsis Campaign resuscitation bundle. In another 4,801 patients who got the bundle, mortality was significantly lower at 28.8%. And, in those who received the bundle plus lactate clearance, mortality further fell to about 22% (J. Intensive Care Med. 2012 [doi:10.1177/0885066612453025]).

Thus, the coming Surviving Sepsis Campaign 2012 guidelines will suggest that in patients with elevated lactate levels as a marker of hypoperfusion, resuscitation should be targeted at normalizing lactate as rapidly as possible (grade 2C). Having said that, however, a normal lactate doesn’t indicate absence of shock. Other factors, such as the patient’s central venous oxygen saturation level, need to be considered as well, the physicians emphasized.

The Surviving Sepsis Campaign guidelines are sponsored by 27 medical organizations. Among them are the Society of Critical Care Medicine, ACEP, the Society of Hospital Medicine, the American College of Chest Physicians, the American Thoracic Society, the Infectious Diseases Society of America, the Surgical Infection Society, the Pediatric Acute Lung Injury and Sepsis Investigators, and a host of international groups.

Dr. Osborn and Dr. Winter reported having no financial conflicts.

DENVER – Look for some big changes ahead in the forthcoming update of the Surviving Sepsis Campaign international guidelines.

In the 4 years since the last version of the guidelines came out, major studies have been released that resolved hot debates regarding sepsis management and in some cases overturned established dogma. At the annual American College of Emergency Physicians (ACEP) meeting, emergency physicians deeply involved in crafting the Surviving Sepsis Campaign 2012 guidelines provided a preview of what’s to come.

Among the areas that will see key new recommendations are antibiotic therapy, fluid resuscitation, vasopressors, and lactate monitoring.

• Antibiotics ASAP. The critical importance of getting empiric antibiotics on board within 6 hours after recognizing that a patient has sepsis has been effectively hammered home over the years. But how fast is fast enough? Several recent small studies have reached conflicting conclusions. Now, however, an 800-lb gorilla of a study has provided a definitive answer.

This study, now in press, involved 14,895 patients enrolled in the Surviving Sepsis Campaign’s worldwide database. All had severe sepsis or septic shock, and all received antibiotics within the first 6 hours, explained Dr. Tiffany M. Osborn, a coauthor of the study and of the forthcoming guidelines.

"This was a big question for us. The results strengthen the importance of getting antibiotics started as soon as possible – within the first hour if possible. We found there’s about a 4% increase in mortality for every hour delay. And it’s cumulative: it’s 4% after the first hour, 8% after the second, 12% after the third, and so on," according to Dr. Osborn of Washington University at St. Louis.

A similar time-dependent increase in mortality was observed in patients with severe sepsis as well as in those in septic shock, she added.

• Fluid resuscitation. The initial fluid of choice for resuscitation in severe sepsis and septic shock remains crystalloids, as before. That’s a grade 1A recommendation. What’s brand new is a recommendation to consider adding albumin in the initial fluid resuscitation (grade 2B). This guidance was heavily influenced by a meta-analysis of 17 studies involving close to 2,000 patients that demonstrated a significant protective effect for the use of albumin as an initial resuscitation fluid (Crit. Care Med. 2011;39:386-91).

At this late date, Dr. Osborn said, the guideline panel is strongly leaning toward a recommendation against the use of low-molecular-weight colloids or starches such as hydroxyethyl starch 130/0.42. That would be ground shaking, as synthetic colloids or starches, particularly those of low molecular weight, are a very popular resuscitation fluid both in the United States and abroad. However, recent studies implicate these fluids in increased risks of 90-day mortality and renal failure, compared with the use of Ringer’s lactate.

"Having said this, there are two other trials currently pending. Any month now the results will come out, and we’ll see where we are at that point. But at this time, we’re thinking stay away from low-molecular-weight starches for resuscitation," Dr. Osborn said.

One of the main reasons the Surviving Sepsis Campaign 2012 guidelines won’t actually be published before January 2013 is the guideline panel’s eagerness to see the results of those two studies, she added.

• Vasopressor therapy. The initial target remains, as before, a mean arterial pressure of at least 65 mm Hg. But while the 2008 guidelines recommended either norepinephrine or dopamine as the first-choice vasopressor to correct hypotension in patients not sufficiently responsive to fluid resuscitation, the new guidelines will state that norepinephrine is the preferred agent (grade 1B). That’s a major change. Dopamine has been essentially kicked to the curb in response to multiple studies in the last 4 years implicating it in an increased incidence of arrhythmias and, in some studies, higher mortality.

The final nail in dopamine’s coffin for use in patients with severe sepsis or septic shock was a recent meta-analysis involving five observational and six interventional studies totaling nearly 2,800 patients (Crit. Care Med. 2012;40:725-30).

"Dopamine has actually fallen by the wayside. By far and away, I’m going to choose norepinephrine as the initial vasopressor agent," declared Dr. Michael E. Winters of the University of Maryland, Baltimore.

The new guidelines will suggest that be reserved for highly selected patients: those at very low arrhythmia risk and with a low cardiac output and/or low heart rate (grade 2C), he noted.

Another change in the new guidelines will be a recommendation that epinephrine be added when an additional agent is needed in order to maintain adequate blood pressure (grade 2B).

• Don’t overdo the fluids. "We want to give patients what they need but not more," Dr. Osborn explained. The 2012 guidelines will recommend that physicians use some sort of fluid challenge test while administering fluid boluses. The goal is to keep giving fluid only so long as hemodynamic improvement is seen in response. This can be achieved in a variety of ways, including monitoring change in pulse pressure, stroke volume variation, heart rate, or arterial pressure.

• Lactate clearance. Serum lactate is recognized as an indicator of global organ hypoperfusion and shock. But incorporating lactate clearance as one of the goals of early sepsis therapy has been "a very hot topic," Dr. Winters observed.

Improved clarity was provided by a prospective 556-patient quality improvement study by investigators in the Asian Network to Regulate Sepsis Care. Patients who got the primary severe sepsis management bundle of care as recommended in the 2008 Surviving Sepsis Campaign guidelines had an unadjusted mortality of 43.6%. This bundle includes early antibiotic administration, hemodynamic monitoring and support, and achievement of a central venous oxygen saturation level greater than 70% by 6 hours. However, patients who got the bundle plus lactate clearance had a 20.5% mortality rate (Crit. Care 2011;15:R229 [doi:10.1186/cc10469]).

The importance of lactate clearance was further underscored by the findings in the GENESIS Project (Generalized Early Sepsis Intervention Strategies). This quality improvement initiative, conducted at five 5 U.S. community hospitals and six tertiary centers, showed a 42.8% mortality in 1,554 historical controls treated for sepsis before implementation of the Surviving Sepsis Campaign resuscitation bundle. In another 4,801 patients who got the bundle, mortality was significantly lower at 28.8%. And, in those who received the bundle plus lactate clearance, mortality further fell to about 22% (J. Intensive Care Med. 2012 [doi:10.1177/0885066612453025]).

Thus, the coming Surviving Sepsis Campaign 2012 guidelines will suggest that in patients with elevated lactate levels as a marker of hypoperfusion, resuscitation should be targeted at normalizing lactate as rapidly as possible (grade 2C). Having said that, however, a normal lactate doesn’t indicate absence of shock. Other factors, such as the patient’s central venous oxygen saturation level, need to be considered as well, the physicians emphasized.

The Surviving Sepsis Campaign guidelines are sponsored by 27 medical organizations. Among them are the Society of Critical Care Medicine, ACEP, the Society of Hospital Medicine, the American College of Chest Physicians, the American Thoracic Society, the Infectious Diseases Society of America, the Surgical Infection Society, the Pediatric Acute Lung Injury and Sepsis Investigators, and a host of international groups.

Dr. Osborn and Dr. Winter reported having no financial conflicts.