EDEN Trial Questions Restricting Nutrition to ALI Patients

HOUSTON – Restricting the amount of initial enteral intake in mechanically ventilated patients who have acute lung injury neither reduces the duration of mechanical ventilation nor improves mortality relative to full enteral feeding, but the nutritional strategy may be slightly easier on the stomach, according to a study reported Feb. 5 at the annual meeting of the Society of Critical Care Medicine Critical Care Congress.

The importance of nutrition support in critically ill patients with acute lung injury (ALI) is well accepted as a means of maintaining gut integrity, modulating both stress and the systemic immune response, and attenuating disease severity, but conflicting data regarding the timing, formulation, and amount of enteral nutrition have contributed to uncertainty about the optimal feeding protocol, according to Dr. Todd W. Rice of Vanderbilt University Medical Center in Nashville, Tenn.

"How much nutrition we need to promote the protective benefits, we don’t know. Providing a little bit of nutrition (called trophic feeding) has been shown to decrease intestinal intolerances, compared with full-calorie feeds, but it may do so at the risk of malnutrition, worse immune function, and loss of muscle strength," he said. Full-calorie feeding, on the other hand, may lead to more intolerances, may cause hyperglycemia and other imbalances, may increase septic complications, and may fuel the inflammatory fire, he added.

In the current study, which was published simultaneously in JAMA, Dr. Rice and colleagues in the EDEN (Early Vs. Delayed Enteral Nutrition in ALI) trial, sought to examine the relative advantages of restricting the amount of initial enteral intake in mechanically ventilated ALI patients. Specifically, the prospective, randomized, open-label trial compared the effect on clinical outcomes and survival of initial trophic enteral feeding – approximately 25% of the full target feeding – with initial full-calorie feeding for the first 6 days of mechanical ventilation in ALI patients. "We hypothesized that reduced trophic feeding during the first [6 days] would increase ventilator-free days and reduce instances of gastrointestinal intolerances compared with the conventional full enteral nutrition strategy," he said.

"How much nutrition we need to promote the protective benefits, we don’t know."

The study’s primary end point was ventilator-free days through day 28; secondary end points were daily percentage of goal enteral feeding, frequency of gastrointestinal intolerances, 60-day mortality before hospital discharge with unassisted breathing, ICU- and organ failure–free days, and new infections (JAMA 2012 Feb. 5 [doi:10.1001/jama2012.137]).

The multicenter study population comprised 1,000 patients, from January 2008 through mid-April 2011, who were initiated on mechanical ventilation within 48 hours of developing ALI. Within 6 hours of randomization, enteric nutrition was initiated in 508 patients assigned to trophic nutrition and 492 assigned to full feeding, and was continued until death, extubation, or day 6, Dr. Rice explained. Per standard protocol, enteral nutrition in the full-feeding group began at 25 mL/hr and advanced to goal weights (25-30 kcal/day of nonprotein calories and 1.2-1.6 g/kg per day of protein) as quickly as possible; gastric residual volumes were checked every 6 hours while enteral feeding was increased. In the trophic group, enteral feeding was initiated at 10-20 kcal/hr and gastric residual volumes were checked every 12 hours. After 6 days, patients in the trophic group who still required mechanical ventilation were advanced to the full-energy feeding rates, he said.

Baseline characteristics of the two groups were similar, Dr. Rice noted. "The primary etiologies of lung injury in both groups of patients were pneumonia and sepsis, and the average APACHE III [Acute Physiology and Chronic Health Evaluation III] score was approximately 92. These were sick patients," he said. For the first 6 days, the full- and trophic feeding groups received 1,300 kcal/day and 400 kcal/day, respectively.

With respect to the primary end point (28 days), the average number of ventilator-free days in both groups was similar, at 14.9 in the trophic group and 15.0 in the full-feeding group. "There were also no differences in 60-day mortality, organ failure–free days, ICU-free days, or the incidence of infection between groups," he said. Similarly, with respect to body mass index category or lung injury severity, "there were no between-group differences in ventilator free days or survival."

The full-feeding group did have a higher number of gastrointestinal intolerances on any one day, and statistically significant increase on days 2 and 3, but the overall percentages of intolerances were low, Dr. Rice said. There were no differences in albumin and protein levels between the groups over the first 7 days, he said.

Regarding the immediate clinical relevance of the findings, Dr. Rice stressed that the study wasn’t designed as an equivalence trial, "so I can’t tell you both feeding strategies are similar, but you can look at the results." In fact, he said, although the study did not show a benefit other than improved gastrointestinal tolerance, his group has moved toward trophic feeds because of the ease of administration. "Our nurses love the trophic feeds. Starting at 10-20 cc/hr and running it for 6 days is a lot less hassle than worrying about trying to ramp it up and get to goals," he said.

"Looking ahead, there are a number of places to go" with this research, Dr. Rice said. "Some of the questions we’ve thought about are what role does this play in the [total parenteral nutrition] question, and whether we need to be feeding patients at all. Initially, we thought the idea of not feeding patients would be a hard study to sell, but with these data, it may not be an unreasonable thing to look at."

Dr. Rice disclosed no financial conflicts of interest.

HOUSTON – Restricting the amount of initial enteral intake in mechanically ventilated patients who have acute lung injury neither reduces the duration of mechanical ventilation nor improves mortality relative to full enteral feeding, but the nutritional strategy may be slightly easier on the stomach, according to a study reported Feb. 5 at the annual meeting of the Society of Critical Care Medicine Critical Care Congress.

The importance of nutrition support in critically ill patients with acute lung injury (ALI) is well accepted as a means of maintaining gut integrity, modulating both stress and the systemic immune response, and attenuating disease severity, but conflicting data regarding the timing, formulation, and amount of enteral nutrition have contributed to uncertainty about the optimal feeding protocol, according to Dr. Todd W. Rice of Vanderbilt University Medical Center in Nashville, Tenn.

"How much nutrition we need to promote the protective benefits, we don’t know. Providing a little bit of nutrition (called trophic feeding) has been shown to decrease intestinal intolerances, compared with full-calorie feeds, but it may do so at the risk of malnutrition, worse immune function, and loss of muscle strength," he said. Full-calorie feeding, on the other hand, may lead to more intolerances, may cause hyperglycemia and other imbalances, may increase septic complications, and may fuel the inflammatory fire, he added.

In the current study, which was published simultaneously in JAMA, Dr. Rice and colleagues in the EDEN (Early Vs. Delayed Enteral Nutrition in ALI) trial, sought to examine the relative advantages of restricting the amount of initial enteral intake in mechanically ventilated ALI patients. Specifically, the prospective, randomized, open-label trial compared the effect on clinical outcomes and survival of initial trophic enteral feeding – approximately 25% of the full target feeding – with initial full-calorie feeding for the first 6 days of mechanical ventilation in ALI patients. "We hypothesized that reduced trophic feeding during the first [6 days] would increase ventilator-free days and reduce instances of gastrointestinal intolerances compared with the conventional full enteral nutrition strategy," he said.

"How much nutrition we need to promote the protective benefits, we don’t know."

The study’s primary end point was ventilator-free days through day 28; secondary end points were daily percentage of goal enteral feeding, frequency of gastrointestinal intolerances, 60-day mortality before hospital discharge with unassisted breathing, ICU- and organ failure–free days, and new infections (JAMA 2012 Feb. 5 [doi:10.1001/jama2012.137]).

The multicenter study population comprised 1,000 patients, from January 2008 through mid-April 2011, who were initiated on mechanical ventilation within 48 hours of developing ALI. Within 6 hours of randomization, enteric nutrition was initiated in 508 patients assigned to trophic nutrition and 492 assigned to full feeding, and was continued until death, extubation, or day 6, Dr. Rice explained. Per standard protocol, enteral nutrition in the full-feeding group began at 25 mL/hr and advanced to goal weights (25-30 kcal/day of nonprotein calories and 1.2-1.6 g/kg per day of protein) as quickly as possible; gastric residual volumes were checked every 6 hours while enteral feeding was increased. In the trophic group, enteral feeding was initiated at 10-20 kcal/hr and gastric residual volumes were checked every 12 hours. After 6 days, patients in the trophic group who still required mechanical ventilation were advanced to the full-energy feeding rates, he said.

Baseline characteristics of the two groups were similar, Dr. Rice noted. "The primary etiologies of lung injury in both groups of patients were pneumonia and sepsis, and the average APACHE III [Acute Physiology and Chronic Health Evaluation III] score was approximately 92. These were sick patients," he said. For the first 6 days, the full- and trophic feeding groups received 1,300 kcal/day and 400 kcal/day, respectively.

With respect to the primary end point (28 days), the average number of ventilator-free days in both groups was similar, at 14.9 in the trophic group and 15.0 in the full-feeding group. "There were also no differences in 60-day mortality, organ failure–free days, ICU-free days, or the incidence of infection between groups," he said. Similarly, with respect to body mass index category or lung injury severity, "there were no between-group differences in ventilator free days or survival."

The full-feeding group did have a higher number of gastrointestinal intolerances on any one day, and statistically significant increase on days 2 and 3, but the overall percentages of intolerances were low, Dr. Rice said. There were no differences in albumin and protein levels between the groups over the first 7 days, he said.

Regarding the immediate clinical relevance of the findings, Dr. Rice stressed that the study wasn’t designed as an equivalence trial, "so I can’t tell you both feeding strategies are similar, but you can look at the results." In fact, he said, although the study did not show a benefit other than improved gastrointestinal tolerance, his group has moved toward trophic feeds because of the ease of administration. "Our nurses love the trophic feeds. Starting at 10-20 cc/hr and running it for 6 days is a lot less hassle than worrying about trying to ramp it up and get to goals," he said.

"Looking ahead, there are a number of places to go" with this research, Dr. Rice said. "Some of the questions we’ve thought about are what role does this play in the [total parenteral nutrition] question, and whether we need to be feeding patients at all. Initially, we thought the idea of not feeding patients would be a hard study to sell, but with these data, it may not be an unreasonable thing to look at."

Dr. Rice disclosed no financial conflicts of interest.

HOUSTON – Restricting the amount of initial enteral intake in mechanically ventilated patients who have acute lung injury neither reduces the duration of mechanical ventilation nor improves mortality relative to full enteral feeding, but the nutritional strategy may be slightly easier on the stomach, according to a study reported Feb. 5 at the annual meeting of the Society of Critical Care Medicine Critical Care Congress.

The importance of nutrition support in critically ill patients with acute lung injury (ALI) is well accepted as a means of maintaining gut integrity, modulating both stress and the systemic immune response, and attenuating disease severity, but conflicting data regarding the timing, formulation, and amount of enteral nutrition have contributed to uncertainty about the optimal feeding protocol, according to Dr. Todd W. Rice of Vanderbilt University Medical Center in Nashville, Tenn.

"How much nutrition we need to promote the protective benefits, we don’t know. Providing a little bit of nutrition (called trophic feeding) has been shown to decrease intestinal intolerances, compared with full-calorie feeds, but it may do so at the risk of malnutrition, worse immune function, and loss of muscle strength," he said. Full-calorie feeding, on the other hand, may lead to more intolerances, may cause hyperglycemia and other imbalances, may increase septic complications, and may fuel the inflammatory fire, he added.

In the current study, which was published simultaneously in JAMA, Dr. Rice and colleagues in the EDEN (Early Vs. Delayed Enteral Nutrition in ALI) trial, sought to examine the relative advantages of restricting the amount of initial enteral intake in mechanically ventilated ALI patients. Specifically, the prospective, randomized, open-label trial compared the effect on clinical outcomes and survival of initial trophic enteral feeding – approximately 25% of the full target feeding – with initial full-calorie feeding for the first 6 days of mechanical ventilation in ALI patients. "We hypothesized that reduced trophic feeding during the first [6 days] would increase ventilator-free days and reduce instances of gastrointestinal intolerances compared with the conventional full enteral nutrition strategy," he said.

"How much nutrition we need to promote the protective benefits, we don’t know."

The study’s primary end point was ventilator-free days through day 28; secondary end points were daily percentage of goal enteral feeding, frequency of gastrointestinal intolerances, 60-day mortality before hospital discharge with unassisted breathing, ICU- and organ failure–free days, and new infections (JAMA 2012 Feb. 5 [doi:10.1001/jama2012.137]).

The multicenter study population comprised 1,000 patients, from January 2008 through mid-April 2011, who were initiated on mechanical ventilation within 48 hours of developing ALI. Within 6 hours of randomization, enteric nutrition was initiated in 508 patients assigned to trophic nutrition and 492 assigned to full feeding, and was continued until death, extubation, or day 6, Dr. Rice explained. Per standard protocol, enteral nutrition in the full-feeding group began at 25 mL/hr and advanced to goal weights (25-30 kcal/day of nonprotein calories and 1.2-1.6 g/kg per day of protein) as quickly as possible; gastric residual volumes were checked every 6 hours while enteral feeding was increased. In the trophic group, enteral feeding was initiated at 10-20 kcal/hr and gastric residual volumes were checked every 12 hours. After 6 days, patients in the trophic group who still required mechanical ventilation were advanced to the full-energy feeding rates, he said.

Baseline characteristics of the two groups were similar, Dr. Rice noted. "The primary etiologies of lung injury in both groups of patients were pneumonia and sepsis, and the average APACHE III [Acute Physiology and Chronic Health Evaluation III] score was approximately 92. These were sick patients," he said. For the first 6 days, the full- and trophic feeding groups received 1,300 kcal/day and 400 kcal/day, respectively.

With respect to the primary end point (28 days), the average number of ventilator-free days in both groups was similar, at 14.9 in the trophic group and 15.0 in the full-feeding group. "There were also no differences in 60-day mortality, organ failure–free days, ICU-free days, or the incidence of infection between groups," he said. Similarly, with respect to body mass index category or lung injury severity, "there were no between-group differences in ventilator free days or survival."

The full-feeding group did have a higher number of gastrointestinal intolerances on any one day, and statistically significant increase on days 2 and 3, but the overall percentages of intolerances were low, Dr. Rice said. There were no differences in albumin and protein levels between the groups over the first 7 days, he said.

Regarding the immediate clinical relevance of the findings, Dr. Rice stressed that the study wasn’t designed as an equivalence trial, "so I can’t tell you both feeding strategies are similar, but you can look at the results." In fact, he said, although the study did not show a benefit other than improved gastrointestinal tolerance, his group has moved toward trophic feeds because of the ease of administration. "Our nurses love the trophic feeds. Starting at 10-20 cc/hr and running it for 6 days is a lot less hassle than worrying about trying to ramp it up and get to goals," he said.

"Looking ahead, there are a number of places to go" with this research, Dr. Rice said. "Some of the questions we’ve thought about are what role does this play in the [total parenteral nutrition] question, and whether we need to be feeding patients at all. Initially, we thought the idea of not feeding patients would be a hard study to sell, but with these data, it may not be an unreasonable thing to look at."

Dr. Rice disclosed no financial conflicts of interest.