Abstract & Commentary

TPN? And When?

By Saadia R. Akhtar, MD, MSc, St. Luke's Idaho Pulmonary Associates, Boise, is Associate Editor for Critical Care Alert.

Dr. Akhtar reports no financial relationships relevant to this field of study.

Synopsis: This randomized multicenter trial of the timing of initiation of parenteral nutrition for supplementation of enteral nutrition for ICU patients finds improved outcomes and fewer complications with late initiation.

Source: Casaer MP, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med 2011;365:506-517.

Casaer et al set out to determine the effects of late (day 8) vs early (within 48 hours) initiation of parenteral nutrition (TPN) on death rate and complications in adult intensive care unit (ICU) patients. The primary endpoint was number of days in the ICU.

This was a prospective, randomized, controlled, multicenter trial that took place between 2007 and 2010 at seven ICUs in Belgium. Inclusion criteria were evidence of nutritional impairment or significant risk for it (measured using a validated and standardized nutritional risk screen questionnaire) and age > 18 years. Exclusion criteria included being severely underweight (defined by body mass index), already being on nutritional supplementation, recent admission to the ICU, diabetic coma or moribund state, and absence of central venous catheter. Caloric targets were calculated for each patient. All patients began enteral nutrition by day 2 if unable to eat; semi-recumbent position was maintained. For the early-initiation group, a 20% glucose solution (D20) was administered intravenously for the first 2 days and then full TPN was started on day 3. For the late-initiation group, 5% glucose (D5) was given intravenously; if enteral nutrition was felt to be inadequate by day 8, TPN was added. Aggressive blood glucose control (80-110 mg/dL) was maintained with continuous infusion of intravenous insulin. TPN was stopped once at least 80% of calorie goal was met with enteral nutrition (or once the patient started to eat). Usual demographic, clinical, and outcome data were collected along with 90-day vital status. The authors applied appropriate randomization schemes, interim analysis, and statistical methods.

A total of 4640 patients were enrolled and randomized. Subjects were well-matched in terms of baseline characteristics. The late-initiation group had lower insulin needs and more hypoglycemic episodes. Despite this, ICU median length of stay (LOS) was 1 day shorter; risk of acquiring new infections was less; and duration of mechanical ventilation, renal replacement, and hospitalization were shorter in this group; there was also a mean cost reduction of about $1600 per patient. Functional status at hospital discharge and mortality at ICU and hospital discharge and 90 days were similar in the two groups.


An essential component of supportive care for any critical illness is nutrition, which serves to meet patients' metabolic needs and facilitate recovery. Although limited data demonstrate some benefits of enteral compared to parenteral nutrition (e.g., reduced infections, lower cost), both methods may have complications. Patients receiving enteral nutrition may develop aspiration (with subsequent pneumonia), diarrhea, or constipation. Administration of TPN may lead to thromboses or bloodstream infections related to the central venous access. Hyperglycemia and other metabolic abnormalities and fluid imbalance can be a concern with either method of nutritional support. In general, recent practice has been to favor enteral nutrition with aspiration precautions and careful blood glucose control; however, it has been unclear whether or when to add TPN if caloric targets cannot be met with enteric feeding alone.

This study provides some useful information, showing that early initiation of TPN in ICU patients is associated with worse outcomes. It is important though to note that although the relative benefits of late initiation of TPN in this study were significant, they were small; for example, a 1-day difference in ICU LOS and 3.4% difference in new infections, without an impact on mortality. Furthermore, the majority of patients studied were being admitted for elective cardiac surgery and had good baseline nutritional status. It is difficult to know whether these results apply consistently to sicker, malnourished ICU patients.

I suggest initiating enteral nutrition within the first 2-3 days of a patient's admission to the ICU whenever possible. If goal caloric intake cannot be achieved rapidly, it is prudent to wait and tolerate some degree of underfeeding for the first week. The exception to this may be the patients who have very significant malnutrition at baseline; here, our individual clinical judgments about initiation of TPN must prevail until further clinical trials are completed.