Jim Kling

May 21, 2015

DENVER — Calorie restriction lowers blood sugar levels, reduces insulin use, and improves renal outcomes in critically ill adults, according to a new study.

Observational evaluations have yielded conflicting information on whether full caloric intake as soon as possible reduces malnutrition and protein loss in critically ill patients.

However, "those studies were seriously confounded by many variables," Yaseen Arabi, MD, from the King Saud bin Abdulaziz University for Health Sciences in Riyadh, Saudi Arabia, told Medscape Medical News.

The results "triggered this larger trial, which was multicentered," said Dr Arabi, who presented the research here at the American Thoracic Society 2015 International Conference. The study was published online in the New England Journal of Medicine to coincide with its presentation.

Recent evidence indicating that lowering calorie intake can lengthen lifespan and improve mortality has prompted researchers to wonder if the strategy might improve outcomes in critically ill patients.

Randomized controlled trials conducted in patients with acute respiratory failure (Crit Care Med. 2011;39:967-974) and acute lung injury (JAMA. 2012;307:795-803) showed no benefit to underfeeding, but neither of those studies involved protein supplementation in the underfeeding group.

In contrast, in a previous randomized controlled that Dr Arabi was involved in, a low-calorie diet with protein supplementation did reduce in-hospital mortality (Am J Clin Nutr. 2011;93:569-577).

Underfeeding vs Target Feeding

To evaluate the potential benefits of underfeeding, the researchers compared two regimens: permissive underfeeding, which consisted of 40% to 60% of calculated caloric requirements; and target feeding, which consisted of 70% to 100% of caloric requirements.

The 894 critically ill adults from seven centers in Canada and Saudi Arabia were randomized to permissive underfeeding or to target feeding for up to 14 days.

The study was unblinded. Patients in the underfeeding group received additional protein and normal saline or water enterally every 4 hours.

The average proportion of caloric requirement was lower in the underfeeding group than in the target group (46% vs 72%; P < .0001).

Protein intake was similar in the two groups. However, glucose levels were lower in the underfeeding group than in the target group (9.1 vs 9.4 mmol/L; = .04), fewer patients received insulin in the underfeeding group (45.8% vs 52.7%; P = .04), and units of insulin per day were lower in the underfeeding group (15 vs 22; P = .02).

No Mortality Benefit

There was no difference in 90-day mortality between the underfeeding and target groups (27.2% vs 28.9%; relative risk [RR], 0.96; 95% confidence interval [CI], 0.76 - 1.16; P = .58).

Although new renal replacement therapy was required less frequently in the underfeeding group than in the target group (7.2% vs 12.4 %; RR, 0.66; 95% CI, 0.49 - 0.89; P = .01), this was not a predefined end point.

Both groups received the same amount of protein, and there was no difference between the groups in terms of various markers of protein metabolism, such as nitrogen balance and levels of prealbumin, transferrin, and urinary nitrogen excretion. "Giving them more calories didn't build protein," Dr Arabi reported.

Feeding people less than their full needs is not a terrible thing. It doesn't kill people.

There was also no difference between the two groups in serum potassium, magnesium, phosphate, prealbumin, transferrin, blood transfusions, diarrhea, gastric intolerance, infections acquired in the intensive care unit, or length of hospital stay.

"People who got fed more had higher blood sugars and needed more insulin to titrate those blood sugars back down," said session moderator Allan Garland, MD, from the University of Manitoba, in Winnipeg, Canada. "Maybe that's the problem," he told Medscape Medical News.

This study provides some reassurance for physicians considering an underfeeding strategy. "It suggests that feeding people less than their full needs is not a terrible thing. It doesn't kill people," Dr Garland said.

There are many varieties of critical illness. Underfeeding might be beneficial in some cases but not in others, he added. The "feed a cold, starve a fever" adage might be right. There could be a "physiological benefit that we don't really understand."

"A moderate amount of calories is a reasonable approach in the ICU," Dr Arabi advised. "A higher amount of calories is causing people to get more hyperglycemia and more insulin, and maybe more renal failure."

Dr Arabi and Dr Garland have disclosed no relevant financial relationships.

New Engl J Med. Published online May 20, 2015. Abstract

American Thoracic Society (ATS) 2015 International Conference: Abstract A6479. May 20, 2015.


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