Spring has finally arrived in Virginia and our Redbuds and Dogwoods are decorating the landscape of Charlottesville. We had a great week with our nutrition support trainees who hailed from Provo, Utah; St. Clair, Michigan; Pittsburgh, Pennsylvania; and Fredericksburg, Virginia. Our journal club this month is on an article that promises to be a source of substantial discussion in the future.
Singer P, Anbar R, Cohen J, et al. The tight calorie control study (TICACOS): a prospective, randomized, controlled pilot study of nutritional support in critically ill patients. Intensive Care Med. 2011;37(4):601-9.
This was a randomized, unblinded pilot study in a mixed ICU where patients were assigned to receive nutrition support with calorie goals determined by either:
- Every other day indirect calorimetry (IC), or “tight calorie group”
- 25 calories/kg (control)
Patients in both groups were started on enteral nutrition (EN); parenteral nutrition (PN) was used to make up any calorie deficits between the amount of enteral calories infused and the actual calorie goal. The tight calorie group had every other day IC measurements and the dietitian “in charge of the study was responsible for ensuring the achievement of energy targets.” The control group had a calorie goal determined by 25 calories/kg of pre-admission weight and all adjustments for any calorie deficit were, “left to the responsibility of the ward staff according to the routine nutrition protocol.” Continuous insulin infusions were used to maintain blood glucose levels below 150 mg/dl in both groups.
Primary endpoint: improved hospital survival
Secondary outcomes included:
- Length of mechanical ventilation, ICU and hospital stay
- ICU mortality
- Development of new pressure sores
- Requirement for unplanned surgery and surgical complications
- Incidence of renal impairment,
- Incidence of new onset liver impairment
- Infectious complications
Inclusion and Exclusion Criteria were:
- Age ≥ 18 years
- Admitted to the ICU
- Mechanically ventilated
- Expected ICU stay > 3 days
- FiO2 requirement > 0.6
- Air leaks
- Inhaled nitric oxide
- Continuous renal replacement therapy
- Head Trauma
- Severe liver disease
- Post open-heart surgery
Major Results reported by authors:
The investigators screened 944 patients, 130 of which were eligible and subsequently randomized for the study, but only 112 patients completed the full protocol. Study patients received significantly more calories and protein than the control patients: 2086 +/- 460 calories, 76 +/- 16 gm protein vs. 1480 +/- 356 calories, 53 +/- 16 gm protein. In the primary outcome of hospital mortality, according to intention-to-treat analysis (all patients randomized), there was no statistically significant difference between the groups. However, there was a trend towards reduced hospital mortality in the study group compared to control (32.3% vs 47.7% respectively, p =0.058). When hospital mortality was analyzed with the “per protocol” group of 112 patients (less those excluded after randomization), hospital mortality was significantly less in the study group compared to control group (28.5% vs 48.2% respectively, p= 0.023).
ICU mortality was not significantly different between the groups, but length of ICU stay and duration of mechanical ventilation were both significantly longer in the tight calorie group (p=0.04 and p=0.03 respectively); total infection rate was also significantly greater compared to the control group (37 vs 20 respectively, p= 0.05). Daily mean blood glucose was not significantly different between the groups.
The authors concluded that, “a bundle comprising actively supervised nutritional intervention and providing near target energy requirements based on repeated energy measurements using both EN and PN was achievable in a general ICU and may be associated with lower hospital mortality. However, this was also associated with prolonged duration of mechanical ventilation and ICU stay. We believe that these findings should be confirmed by larger, prospective, multi-center studies.”
This study attempts to addresses a controversial question in nutrition support – the need to measure actual calorie expenditure and provide nutrition that meets or exceeds full calorie expenditure in the ICU. However, the use of indirect calorimetry was not the only difference between these two groups of patients. The study group had a dietitian responsible for ensuring the achievement of energy targets – as pointed out in the conclusions – this was a “bundle” approach.
To understand the results of this study it is important to note that actual energy expenditures of the control group were also measured, and in the table provided it is apparent that the mean measured energy expenditure values of the control group were virtually the same as the calculated target of 25 calories/kg! Although the target calorie goal of the two groups were not very different, the actual calories and protein provided were significantly greater in the study group. The study group actually received more calories than they expended, with a cumulative energy balance of +2008 +/- 2177 compared to the negative energy balance of the control of -3550 +/- 4591 (p=0.01).
The major difference between these two groups is the amount of parenteral nutrition provided to the study group. The average EN provided was not significantly different between the groups (p=0.09). However, the study group received significantly greater parenteral calories (p=0.001), and had more than twice as many patients received PN in addition to EN in the study group as the control (19 vs 7 respectively). The study group also received significantly more protein than the control group (p=0.01). We noted that based on the mean weight and protein values that the control group received an average of only 19 calories and 0.8 gm protein per kg.
After carefully looking at the methods of this study, our group strongly felt that this study told us very little about the benefits or drawbacks of indirect calorimetry, but did provide some information about the effects of supplementing enteral calories with PN. Most notable is the significantly increased infections, increased time on the ventilator and increased time in the ICU that occurred in the control group when supplemental PN was added to EN, even in the setting of good glucose control.
This was a pilot study of relatively modest size. Certainly 130 patients is far too small to make strong statements regarding mortality in such a heterogeneous critically ill population, and as the authors appropriately point out, these results need to be confirmed by larger multi-center studies. We also noted that mortality rate in the control group of 47.7% is much higher than we would expect from a similar population in our hospital, and even more striking was the mortality rate of 21.5% of floor patients that had survived the ICU.
Another way in which this population appeared to be different than the patients that we care for was the duration of the hospital stay. Mean hospital stay was 33.8 days in the study group and 31.8 days in the control group.
It is certainly conceivable that a large cumulative calorie and protein deficit can increase complications, delay recovery and even increase hospital mortality, especially in patients with preexisting malnutrition or extended hospitalizations. However, much larger studies would be necessary to establish the potential benefits of full nutrition, keeping in mind that a cleaner study would not add parenteral nutrition as a confounding variable.
Our Take Home messages:
1. The addition of PN to EN in the ICU appears to significantly increase infectious complications, delay ventilator weaning and increase length of stay in the ICU, even with good glucose control.
2. Nutrition support consultants can minimize the cumulative calorie deficits that accrue in many critically ill patients when they are dedicated to do so.
3. Large cumulative nutrition deficits may have a negative impact on hospital mortality in patients with extended hospitalizations, but large multi-centered trials are required to answer this question.
See our website: www.ginutrition.virginia.edu for:
Upcoming Webinars for Spring/Summer 2011:
- May 17: Gastric versus Jejunal Feeding: Combining Data and Clinical Judgment—Joe Krenitsky, MS, RD
- June 14: Small Bowel Bacterial Overgrowth–Carol Parrish, MS, RD
- July 19: Feeding the Post-Surgical Patient–Kate Willcutts, MS, RD, CNSC
Latest Practical Gastroenterology articles:
- Krenitsky J. Blind Bedside Placement of Feeding Tubes: Treatment or Threat? Practical Gastroenterology 2011;XXXV(3):32-42.
- McCray, S, Parrish CR. Nutritional Management of Chyle Leaks: An Update. Practical Gastroenterology 2011;XXXV(4):12.
Joe Krenitsky MS, RD
Carol Rees Parrish MS, RD
PS – Please feel free to forward on to friends and colleagues.