The tight calorie control study (TICACOS): a prospective, randomized, controlled pilot study of nutritional support in critically ill patients
Abstract
Purpose To determine whether nutritional support guided by repeated measurements of resting energy requirements improves the outcome of critically ill patients.Methods This was a prospective, randomized, single-center, pilot clinical trial conducted in an adult general intensive care (ICU) unit. The study population comprised mechanically ventilated patients (n = 130) expected to stay in ICU more than 3 days. Patients were randomized to receive enteral nutrition (EN) with an energy target determined either (1) by repeated indirect calorimetry measurements (study group, n = 56), or (2) according to 25 kcal/kg/day (control group, n = 56). EN was supplemented with parenteral nutrition when required.Results The primary outcome was hospital mortality. Measured pre-study resting energy expenditure (REE) was similar in both groups (1,976 ± 468 vs. 1,838 ± 468 kcal, p = 0.6). Patients in the study group had a higher mean energy (2,086 ± 460 vs. 1,480 ± 356 kcal/day, p = 0.01) and protein intake (76 ± 16 vs. 53 ± 16 g/day, p = 0.01). There was a trend towards an improved hospital mortality in the intention to treat group (21/65 patients, 32.3% vs. 31/65 patients, 47.7%, p = 0.058) whereas length of ventilation (16.1 ± 14.7 vs. 10.5 ± 8.3 days, p = 0.03) and ICU stay (17.2 ± 14.6 vs. 11.7 ± 8.4, p = 0.04) were increased.Conclusions In this single-center pilot study a bundle comprising actively supervised nutritional intervention and providing near target energy requirements based on repeated energy measurements was achievable in a general ICU and may be associated with lower hospital mortality.
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If indirect calorimetry is not available, calculation of REE from VCO2 only obtained from ventilators (REE = VCO2 x 8.19) has been demonstrated to be more accurate than equations but less than indirect calorimetry.
“If indirect calorimetry is not available, calculation of REE from VCO2 only obtained from ventilators (REE = VCO2 x 8.19) has been demonstrated to be more accurate than equations (124) but less than indirect calorimetry (125).”
From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [124]
The pilot TICACOS study showed that a strategy using indirect calorimetry was associated with an improvement in 60 day survival in the per protocol study, but also to an increase in length of ventilation, infections and length of stay related to calorie overload and positive energy balance due to non-nutritional energy intakes.
“The pilot TICACOS study [46] showed that such a strategy was associated with an improvement in 60 day survival in the per protocol study, but also to an increase in length of ventilation, infections and length of stay related to the calorie overload and positive energy balance due to non-nutritional energy intakes.”
From ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit (2023) · cites this paper as [46]
In the TICACOS study, despite a large difference in cumulative energy balance between groups, the IC-guided group tended to overfeed while the control group was underfed, and a negative result was observed.
“In the TICACOS study, despite the large difference of cumulative energy balance between groups, the IC-guided group tends to overfeed, while the control group was underfed. Thus, a negative result was observed [7].”
From Energy delivery guided by indirect calorimetry in critically ill patients: a systematic review and meta-analysis (2021) · cites this paper as [7]
The U-shaped relationship between caloric supply and mortality may help explain the negative results of some included trials.
“This may help to explain the negative results of some included trials [7, 20].”
From Energy delivery guided by indirect calorimetry in critically ill patients: a systematic review and meta-analysis (2021) · cites this paper as [7]
Tatucu-Babet et al. reviewed only four trials with a total of 398 patients.
“However, the authors reviewed only four trials with a total of 398 patients [7, 20–22].”
From Energy delivery guided by indirect calorimetry in critically ill patients: a systematic review and meta-analysis (2021) · cites this paper as [7]
The TICACOS study reported a significant day-to-day variation in measured REE by IC, though mean EE was comparable between the IC-guided and control groups.
“As shown in the TICACOS study [7], the authors reported a significant day-to-day variation in measured REE by IC, though the mean EE was comparable between the IC-guided and the control groups.”
From Energy delivery guided by indirect calorimetry in critically ill patients: a systematic review and meta-analysis (2021) · cites this paper as [7]
Four RCTs were identified in that meta-analysis, of which two were included in the present meta-analysis.
“Four RCTs were identified, of which two were included in the present meta-analysis [7, 20].”
From Energy delivery guided by indirect calorimetry in critically ill patients: a systematic review and meta-analysis (2021) · cites this paper as [7]
Some included RCTs reached 100% of the IC targets in the first 24 hours after randomization.
“In the current study, some included RCTs reached 100% of the IC targets in the first 24 h after randomization [7, 21].”
From Energy delivery guided by indirect calorimetry in critically ill patients: a systematic review and meta-analysis (2021) · cites this paper as [7]
Similar findings of day-to-day variation were mentioned in other included studies.
“Similar findings were also mentioned in other included studies [7, 13–15].”
From Energy delivery guided by indirect calorimetry in critically ill patients: a systematic review and meta-analysis (2021) · cites this paper as [7]
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- Authors
- Singer, P., Anbar, R., Cohen, J., Shapiro, H., Shalita-Chesner, M., Lev, S., Grozovski, E., Theilla, M., Frishman, S., & Madar, Z.
- Affiliations
- Tel Aviv University (IL)
- Hebrew University of Jerusalem (IL)
- Rabin Medical Center (IL)
- Corresponding author
- Singer, Pierre
- Venue
- Intensive Care Medicine
- Published
- 2011-02-22
- Volume
- 37
- Issue
- 4
- Pages
- 601-609
- ISSN
- 0342-4642 (ISSN-L)
- 1432-1238
- OpenAlex
- W2104388366
- Cited by
- 566
- References
- 2
- Citations by year
- 2026: 17 · 2025: 23 · 2024: 28 · 2023: 26 · 2022: 22 · 2021: 40 · 2020: 43 · 2019: 28 · 2018: 36 · 2017: 40 · 2016: 53 · 2015: 54 · 2014: 50 · 2013: 40 · 2012: 43
- FWCI
- 45.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Intensive Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- nutritional support, critically ill patients, indirect calorimetry, resting energy expenditure, enteral nutrition, energy targeting, mechanical ventilation, in-hospital mortality, protein intake, parenteral nutrition, ICU length of stay
- MeSH terms
- Adult, Aged, Energy Intake, Critical Care, Energy Metabolism, Female, Humans, Intensive Care Units, Male, Middle Aged, Nutritional Requirements, Prospective Studies, Respiration, Artificial, Treatment Outcome, Hospital Mortality, Nutritional Support
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