University of Virginia Health System
Nutrition Support E-Journal Club
Summer is an eventful time in our facility with the graduation of our dietetic interns and arrival of our new medical students, interns, residents, and fellows. Our staff also moves into "summer mode" and rotates time away for vacations, adventures and family gatherings with "toes in the sand, cool drink in hand", so we can return back to a world of consults, journal clubs, lectures and deadlines renewed and refreshed!
NICE-SUGAR Study Investigators. Finfer S, Chittock DR, Su SY, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360:1346-1349.
NICE-SUGAR was a large multicenter, randomized study designed to resolve the question of the potential benefits of intensive insulin therapy in the ICU. The study was conducted in the ICU's of 42 hospitals, with 6104 mixed surgical and medical patients. Patients received either intensive insulin therapy aimed at normoglycemia (glucose 81-108 mg/dL [4.5-6.0mmol/L]) or the "conventional therapy" (essentially a more liberal intensive insulin therapy) with a goal blood glucose of 144-180 mg/dL [8.0-10.0mmol/L]). The primary outcome was 90 day mortality, with secondary outcomes including the incidence of new organ failure, days on mechanical ventilation, renal replacement therapy, incidence of positive blood cultures, and median length of ICU and hospital stay. Nutrition interventions were not standardized, and left to the discretion of individual clinicians.
Inclusion and Exclusion Criteria were:
Inclusion criteria: Patients that were expected to require treatment in the ICU for 3 or more consecutive days, with an arterial line in place or imminently planned as part of routine ICU care.
Exclusion criteria: Patients that were:
- < 18 years of age
- Believed to be at imminent risk of death.
- Admitted for treatment of diabetic ketoacidosis or hyperosmolar state.
- Expected to be eating before the end of the day following admission.
- Previously suffered hypoglycemia without full neurological recovery.
- Considered at abnormally high risk of hypoglycemia (insulin
secreting tumor, history of recurrent hypoglycemia or fulminant hepatic failure).
- Previously enrolled in the study.
- Unable to provide prior informed consent and without a legal surrogate decision maker.
- In the study ICU or another ICU for > 24 hours.
Major Results reported by authors:
The study found that 90 day mortality was significantly greater in the intensive insulin therapy group compared to the conventional insulin group (27.5% versus 24.9% respectively, p = 0.02). There was no significant difference between the two groups in the incidence of new organ failure, days on mechanical ventilation, renal replacement therapy, incidence of positive blood cultures, or median length of ICU or hospital stay. There were significantly more patients that experienced severe hypoglycemia (blood glucose < 40mg/dl [2.2 mmol/L]) in the intensive insulin group as compared to the conventional group (6.8% versus 0.5% respectively, p < 0.001)
The study demonstrated that a blood glucose target of less than 180 mg/dL resulted in lower mortality than a target of 81 to 108 mg/dL. The authors recommend against the use of the lower target in critically ill adults.
The positive aspects of this study include the large number of subjects and multicenter design. Additionally, blood glucose management was standardized between facilities by using a computerized treatment algorithm. Although the study was not blinded, the researchers did not know which group a new patient would be in until they were randomized (concealed assignment).
Our group noted the differences between the earlier Van den Berghe studies (1,2) of intensive insulin and the current study - especially the use of a much lower glucose goal in the conventional group in the NICE SUGAR study (144-180mg/dl). The studies by Van den Berghe et al. did not begin an insulin drip in the conventional group until blood glucose exceeded 215 mg/dl, with a goal of 180-200mg/dl. The NICE SUGAR study really seemed to compare two different levels of intensive insulin therapy. Most clinicians would consider the glucose control in the conventional group (mean glucose 144 mg/dl) to be very good control.
Another difference between the earlier studies and NICE SUGAR was the nutrition support component. The Van den Berghe surgical patient study (1) placed all patients on a glucose drip upon admission providing 680-1020 calories/24 hours, and then patients received parenteral and/or enteral nutrition that provided an average actual 19 calories/kg received. In the NICE SUGAR study patients did not receive over 1000 calories/day from all sources until day 3, and average non-protein calories for the first 14 days were only 891 +/- 490 calories. The amount of nutrition provided to patients in the NICE SUGAR study appears to be significantly less than in the Van den Berghe study, with a greater delay in receiving significant amounts of nutrition in NICE SUGAR. There was no standardized nutrition protocol for NICE SUGAR. If you consider that some patients were likely to have received full nutrition needs, and the low average calorie provision for the first 2 weeks, one wonders how many patients were receiving insulin drips during NICE SUGAR with minimal or no nutrition support. Of course, in daily practice we all see patients that have limited or no nutrition support for some period of time in an ICU, so it can be argued that NICE SUGAR reflects the risks/benefits of ultra-tight glucose control in real-world conditions. It is possible (but remains untested) that some groups of patients may benefit from tighter blood glucose control if they are receiving full, consistent nutrition support.
Another aspect that we noted was that the study was not analyzed using all of the patients that were randomized (intention to treat). Although 6104 patients were randomized, the mortality data was calculated using 6022 patients, the severe hypoglycemia data includes 6030 patients, and the blood culture data 6025 patients.
Our Take Home message:
Intensive insulin therapy in the ICU with a goal of 140-180mg/dl appears to result in improved outcomes compared to intensive insulin therapy designed to "normalize" serum glucose (goal 81-108mg/dl).
- Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345(19):1359-1367.
- Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354(5):449-461.
Check out the Fall schedule of webinar programs at: www.GInutrition.virginia.edu
August 17: Appetite Stimulants-Joe Krenitsky, MS, RD
September 14: Nutrition Support Issues in the Home Care Setting--Gisela Barnadas, RD, CNSC
October 12: Nutrition Support in the Patient with Gastroparesis-Carol Parrish, MS, RD
November 16: Calorie and Protein Determination-Joe Krenitsky, MS, RD
Decemeber (date TBA): Dermatologic Symptoms of Nutrient Deficiency, Maggie Noland, MD
See the latest Practical Gastroenterology article:
Available at: www.GInutrition.virginia.edu
Chan L. Drug Therapy-Related Issues in Patients Who Received Bariatric Surgery (Part I). Practical Gastroenterology 2010; XXXIV (7):26-32.
Joe Krenitsky MS, RD
Carol Rees Parrish MS, RD
PS - Please feel free to forward this on to friends and colleagues.