Submitted: January 10, 2013 Posted: March 16, 2013

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1 Submitted: January 10, 2013 Posted: March 16, 2013 TITLE: Critical Care Nutrition the effect of adequate calorie and protein intake on mortality, ventilator days, ICU and hospital stay: report from a private tertiary care hospital in the Philippines AUTHORS: Manuales, Grace Lina MD (1,2) De Ramos, Monica RND (2) Sinamban, Reynaldo MD (1,2) Llido, Luisito MD (1,2) INSTITUTION WHERE RESEARCH WAS PERFORMED: 1. Clinical Nutrition Fellowship Training Program, St. Luke s Medical Center, 279 E. Rodriguez Sr. Ave., Quezon City, Metro Manila, Philippines Clinical Nutrition Service, St. Luke s Medical Center, 279 E. Rodriguez Sr. Ave., Quezon City, Metro Manila, Philippines 1102 Address for correspondence: E- mail: gracelinamanuales@yahoo.com (Corresponding author: Dr. Grace Lina Manuales) ABSTRACT: Background: Adequate calorie and protein intake has been shown to make a difference in ICU outcomes. There is a need to find out if a nutrition team can help achieve adequate nutrient intake with its beneficial effect on clinical outcomes. Objectives: a) To determine the recommended and actual calorie and protein intake of ICU patients, b) To show the relationship between adequacy of nutrient intake and the following clinical outcomes ICU and hospital mortality rate, length of mechanical ventilator days, length of ICU and hospital stay, and c) To determine if the presence of a nutrition team makes a difference in caloric and protein intake and clinical outcomes of these ICU patients Methodology: All ICU patients admitted between January 2011 and June 2012 with minimum ICU stay of five (5) days were included in the study. Adequacy of calorie and protein were recorded and mortality, number of ventilator days, ICU and hospital stay were documented. Referral or non- referral to the nutrition team was noted. Data were presented as means, medians, and ranges. Chi- square was used for nominal variables, T- tests for numerical variables and Mann- Whitney U test was used for non- normal numerical data. Logistic regression was used to determine the association of adequacy of intake and survival. Significance was set at p <0.05. Results: 80 patients were included in the study. More patients referred to the nutrition team had adequate intake (85.4% vs. 60.3%); 71% of patients with adequate intake were discharged alive; 83% of patients with inadequate intake were not referred to the nutrition team. ICU 1

2 patients who had adequate intake had longer mechanical ventilator days (8 vs. 4.5, p=0.008), longer ICU days (8 vs. 4, p=0.002), and longer hospital days (17 vs. 14, p=0.015). Conclusion: Adequate intake of calorie and protein in ICU patients results to improved mortality, but longer mechanical ventilator days, longer ICU stay and longer hospital stay. Referral to a nutrition team results to more patients achieving adequate intake in both calories and protein. KEYWORDS: adequate, calorie, protein, critical care, mortality, ventilator, ICU, nutrition team INTRODUCTION The hypermetabolic state, increased protein catabolism, increased calorie and protein debt, or combinations of these factors, contribute to malnutrition among patients in the intensive care unit (ICU). The largest negative balances were observed during the first week of ICU stay [1]. This protein- energy deficit occurs in 43 88% of critically ill patients [2]. Inadequate intake is associated with poor clinical outcomes such as increased incidence of nosocomial infections and pressure sores [1,3,8], prolonged length of ICU and hospital stay [1,4], prolonged mechanical ventilation days [1,5] and increased morbidity and mortality [4]. Over- nutrition was also present which was associated with poor outcome(s) [6]. Improvement in clinical outcome(s) among these patients was observed when both energy and protein balances were optimized [7]. The presence of a structured management directed at achieving adequate nutrition intake through a multidisciplinary approach would answer these concerns therefore a clinical nutrition team composed of clinical nutrition physicians, dieticians, nurses, and pharmacists would play a vital role in the management outcome(s) of critically ill patients (9,10,11,12,13). The nutrition committee of St. Luke s Medical Center (SLMC), Metro- Manila, Philippines, started its clinical nutrition program in This program consisted of: a) nutrition screening of all admitted patients, b) nutritional assessment of identified patients at risk of developing malnutrition, c) nutrition care plans development for theses high risk patients, d) monitoring and reevaluation of nutrition management, and redesign of the nutrition care plan if needed. It has a clinical nutrition team composed of clinical nutrition physicians and fellows- in- training in clinical nutrition, clinical dietitians, clinical pharmacists, and nurses. Its main task is to follow- up the need to be seen patient population including patients in the critical care unit [14]. The prevalence of malnutrition in the hospital report in 1995, which defined malnutrition as all underweight, overweight and obese patients, showed that that the malnutrition prevalence in the critical care population, Adult Intensive Care (ICU) and Critical Care Unit (CCU), was 58%. Sixteen years later in 2011, ICU and CCU malnutrition rate, was noted at 21.5% and 21% respectively [15]. In the ICU intake study in 2006, the team noted that the actual calorie and protein intake among its geriatric patients in the ICU did not meet 50% of the computed calorie requirement and 80% of the computed protein requirement [16]. Bridging this deficiency between actual and recommended intake is one of the goals of the team. A report of a ten year experience of the SLMC Clinical Nutrition team on the supervision of nutrient intake among critical care patients showed that the presence of a team can sustain the adequacy of intake of both calorie and protein in the long term [17]. This local study dealt 2

3 with adequacy of intake in critical care patients, however there is no local follow- up study which correlates adequacy of intake with clinical outcomes among ICU patients. The goals of this study are the following: a) To describe the recommended and actual calorie and protein intake of ICU patients, b) To determine the relationship between adequacy of nutrient intake and the following clinical outcomes ICU and hospital mortality rate, length of mechanical ventilator days, length of ICU and hospital stay, and c) To determine if the presence of a nutrition team makes a difference in caloric and protein intake and clinical outcomes of these ICU patients. METHODOLOGY All patients admitted between January 2011 and June 2012 in the Adult Intensive Care Unit of St. Luke s Medical Center, a private tertiary care training hospital, were included in the study. The inclusion criteria were the following: a) 18 years old and above, b) complete nutrition intake record within seven days of ICU stay. The exclusion criteria were: a) incomplete nutrition intake record, b) expired or discharged from the ICU within 48 hours of ICU admission and c) pregnant or lactating. These are the data gathered: a) number of organ dysfunction and/or failure, b) ICU and hospital days, c) mechanical ventilator days, d) status on hospital discharge (mortality) and e) whether patients were referred to the nutrition team or not. Disease specific risk scores during the first twenty- four hours of ICU stay were computed using the simplified acute physiology score II (SAPS) together with its predictive property as to mortality [18]. Determination of energy and protein requirements was based on the actual body weight or the ideal body weight if the actual body weight is not measurable or if the patient is obese and the reference energy and protein values were based on either the ESPEN 2009 [20,21] or the ASPEN 2007 [22] guidelines. The energy and protein requirements were determined either by the clinical nutrition team (for referred patients), or by the attending physician (for non- referred patients). Actual calorie and protein intake within the first seven days of ICU stay were recorded on the ICU data monitoring sheet and intake was considered adequate when 75% of the recommended total calorie and protein requirement was reached. [22] The primary endpoints were a) mortality and b) actual intake achieved, with and without referral to nutrition team. The secondary end points were: a) length of ICU stay, b) length of hospital stay, and c) mechanical ventilator days. ICU stay is considered prolonged if the patient stayed for more than 10 days [23] while prolonged hospital stay is defined as more than 23 days (>75th percentile of all patients) [24, 25]. Mechanical ventilator days are prolonged if patient is intubated for more than 96 hours. These data were presented as means, medians, and ranges. Chi- square was used for nominal variables, T- tests for continuous variables (numerical data) that are normally distributed and Mann- Whitney U test was used for numerical data with non- normal distribution. Logistic regression was used to determine the association of adequacy of intake and survival, as well as of referral to nutrition team and clinical outcomes, after adjustments were made for SAPS II. Statistical significance was set at p value < [19] The software used for the statistical analysis used the NCSS/PASS Dawson edition, version 1 and Stata Version 12. 3

4 RESULTS Patient Profile (Table 1) 80 patients were included in the study of which 58 % are males and 42 % are females with a 1.4:1 male to female ratio. The mean age is 65 years with 46% of patients between 60 and 80 years old. BMI is normal in 64% of patients, underweight in 12%, overweight in 16% and obese in 8%. There are two organ dysfunction and/or failure in 35% of patients; 24% have three, and 26% have four. Sixty- nine percent of patients are on mechanical ventilation while 31% are on either spontaneous or non- invasive ventilation. Mortality rate upon hospital discharge was 28% which coincides with the SAPS II at 45 (40-48), predictive mortality: 34.8 ( ). The route of nutrition delivery is primarily enteral (59%) and parenteral at 27%. The patients were admitted under the following services: medical (69%), surgical (9%) and combined medical- surgical (22%). Table 1. Patient Profile (N=80) Gender Male 46(58%) Female 34(42%) Age distribution (25 & 95yrs) Mean = 65 (SD:17, SE: 1.88) 20 to 40 yrs 10 (12%) 40 to 60 yrs 19 (23%) 60 to 80 yrs 37 (46%) Above 80 yrs 15 (19%) BMI <18.5 (underweight) 10(12%) (normal) 51(64%) (overweight) 13 (16%) >30 (obese) 6 (8%) Number of organ dysfunction one organ dysfunction 19 (24%) two organ dysfunction 28 (35%) three organ dysfunction 21 (26%) four organ dysfunction 12 (15%) On mechanical ventilator (+) mechanical ventilator 55 (69%) (- ) mechanical ventilator 25 (31%) SAPS (median) 45 (40-48) Predictive Mortality (median) 34.8 ( ) Status on Hospital Discharge Alive 58 (72%) Dead 22 (28%) Referral to clinical nutrition team Referred 46 (58%) Non- referred 34 (42%) Route of nutrient delivery 4

5 Nutrient Intake Data (Table 2) Enteral 47(59%) Parenteral 22 (27%) Combined enteral/parenteral 11 (14%) Treatment category Medical 55 (69%) Surgical 7(9%) Medical- surgical 18(22%) In the first 7 days of ICU stay, the mean prescribed total calorie requirement is 1500 kcal/day (25 kcal/kg) for referred and 1600 kcal/day (27 kcal/kg) for non- referred patients. The mean prescribed total protein requirement is 60 gm/day (1.0g/kg) for referred patients and 56 gm/day (0.9gm/kg) for non- referred patients. For the referred patients the mean percent adequacy of calorie intake is 85.4% (20-21 kcal/kg) and for protein intake it is 83.3% (0.75g/kg). For the non- referred patients, the mean percent adequacy in calorie intake is lower at 60.3% (15-16 kcal/kg) and adequacy of protein intake is 67.5% (0.55g/kg). There is significant difference in the actual calorie and protein intake between referred and non- referred patients wherein actual calorie and protein intake was higher among referred patients. Table 2: Calorie and protein intake data Energy and protein intake Referred to the Not referred to P value (median, 95%LCL- 95%UCL) nutrition team the nutrition team Computed calorie requirement 1,500 1,600 <0.001* (kcal/day) [1,500-1,500] [ ] Calorie intake 1, * (kcal/day) [1,089-1,330] [664-1,192] Computed protein requirement * (gm/day) [50-60] [50-60] Protein intake <0.001* (gm/day) [40-49] [24-41] Mean % adequacy in calorie Intake 85.4 [77-92] 60.3 [43-72] <0.001* Mean % adequacy in protein Intake *Mann- Whitney U Test Adequate intake and mortality 83.3 [75-92] 67.5 [ ] <0.008* For the patients who were discharged alive, 41/58 (71%) had adequate intake. Of those who had adequate intake 27/41 (66%) were referred to the clinical nutrition team. For the patients who died, 6/22 (27%) had inadequate intake and from these 5/6 (83%) were not referred to the clinical nutrition team. The odds ratio of patients who had adequate calorie intake to be alive compared to those who had inadequate intake was 0.9 while the odds ratio of patients who had adequate protein intake to be alive compared to those who had inadequate protein intake was

6 Calorie Intake and Clinical Outcome Data (Table 3) Patients with adequate calorie intake had the following outcomes: a) longer mechanical ventilation days (8 days vs. 4.5 days p=0.008), b) longer length of ICU stay (8 days vs. 4 days, p=0.002) and longer length of hospital stay (17 days vs. 14 days, p=0.015). Those who were discharged alive had a) more mechanical ventilation days (7.5 vs. 5 days, p=0.012), b) more prolonged ICU stay (9 vs. 4 days, p=0.002) and c) more prolonged hospital stay (19 vs. 14 days, p=0.008). Table 3: Calorie Intake and Clinical Outcome Data Variable Calorie Adequate Median (95%LCL- 95%UCL) Calorie Inadequate Median (95%LCL- 95%UCL) P- value Mechanical ventilation days 8 (6-11) 4.5 (2-6) 0.008* Alive 7.5 (5-11) 5 (1-6) 0.012* Dead 8 (2-15) Length of ICU stay 8 (6-10) 4 (3-7) 0.002* Alive 9 (6-10) 4 (3-7) 0.002* Dead 7.5 (5-12) 5 (2-17) 0.21 Length of Hospital Stay 17 (14-21) 14 (9-17) 0.015* Alive 19 (14-25) 14 (12-17) 0.008* Dead 11 (7-18) 8 (4-32) *Mann- Whitney U Test Protein Intake and Clinical Outcome Data (Table 4) Patients with adequate protein intake had longer length of ICU stay (8 days vs. 4 days, p=0.005). For the patients who were discharged alive there were more ICU days (9 vs. 4 days, p=0.006) and there was longer hospital stay (6 days vs. 0, p<0.001). Table 4: Protein Intake and Secondary Outcome Data Variable Protein Adequate Median (95%LCL- 95%UCL) Protein Inadequate Median (95%LCL- 95%UCL) P value Mechanical ventilation days 7 (5-9) 6 (2-11) 0.19 Alive (39) 6.5 (4-9) 6 (1-17) 0.37 Dead (16) 8 (2-22) 4 (2-15) 0.15 Length of ICU stay 8 (6-10) 4 (3-7) 0.005* Alive (n=58) 9 (6-10) 4 (3-7) 0.006* Dead (n=22) 7.5 (5-12) 5.5 (2-17) Length of Hospital Stay 17 (13-21) 15 (9-17) 0.07 Alive (n=58) 6 (3-8) 0 (0-2) <0.001* Dead (n=22) 11 (7-31) 8 (4-18)

7 DISCUSSION: Mann- Whitney U Test: *significant The study showed that there was improved survival in critical care patients when calorie and protein intake was adequate within the first week of ICU stay (71% vs. 28%). Adequate intake was seen in patients who were referred to the clinical nutrition team (66%) and it is to be noted that for the patients who died, most of those with inadequate intake were not referred to the nutrition team (83%). Attaining at least 75% of target was primarily due to referral to the nutrition team, which performed these key procedures: implementation of the nutrition care plan and daily monitoring by the clinical nutrition staff. The role of the ICU nurses and clinical pharmacists in carrying out orders, accurate recording of nutrient delivery and balance data were also key to the achievement of adequate intake. The utilization of evidence- based and updated feeding protocols also assured optimal care to these critically ill patients [27] with subsequent improved outcomes [28]. In regard to the secondary clinical outcomes, adequate intake did not translate to shortened mechanical ventilation days, decreased ICU and hospital stay in contrast to previous studies [3,4,28]. Apparently the significant increase in mechanical ventilation days, length of ICU and hospital stay were due to the patients staying longer in the ICU due to the nature of the private practice in this institution where the attending physician may allow patients to stay longer in the ICU although there are already indications that the patient may be transferred out of the unit. Secondly the variables seen in patients with inadequate intake are lesser due to the fact that these patients expired and thus had shorter stay in the unit and the hospital. Comparing absolute energy and protein intake in our study with previous studies may help us draw these conclusions. In our study, the absolute calorie and protein intake for referred patients is 1,238 kcal/d (18-22 kcal/kg/d) and 45 g/kg/d ( g/kg/d), respectively. Our outcomes may be similar to the study of Doig and colleagues [28], after 1241 kcal/d (16 kcal/kg/d) energy and 50.1 gm protein/kg/d (0.65 g/kg/d) were provided in the intervention group. In the ACCEPT study [4], after implementation of algorithms to improve caloric intake, the intervention group received 1264 kcal/day while the control group received 998 kcal/day. In the TICACOS trial [30], a trend towards improved survival (p=0.058) in the study group with a higher mean energy (2,086 ± 460; 20-32kcal/kg) and protein intake (76 ± 16; g/kg/d). All these studies showed improvement in survival, however, results did not reach statistical significance. One of the reasons could be that the calories and protein delivered were below the current recommendations set by most guidelines (ESPEN [55], ASPEN [56]) for critically ill patients. As shown in the study of Villet et al [1], energy deficit that built up during the first week of ICU stay correlated with prolonged ICU days and mechanical ventilation days however, not with mortality. Survival outcome was statistically significant when optimal calorie- protein were provided, as with the study of Weijs et al [29] which provided kcal/day (22-33 kcal/kg) energy and 89+9 ( g/kg/d) proteins. Optimal intake or provision according to guidelines decreases mortality in critically ill patients. ICU acquired weakness was noted to appear 7 days after ICU admission [47,48,49]. Grosu et al [50] observed diaphragmatic thinning within the first 48 hours of mechanical ventilation. Loss of muscle mass showed negative correlation with length of stay and was higher during the first 2 to 3 weeks of immobilization [52]. Low fat- free mass was seen in 37% of patients hospitalized for 1 2 days [53]. Our study population received 0.7 to 0.82 g/kg/day (referred) and 0.4 to 0.68 g/kg/day (non- referred) within 7

8 the first seven days of ICU stay. This is again below the ESPEN [55] (1.3 to 1.5 g/kg/day) and ASPEN [56] (1.2 to 2.0 g/kg/day) guidelines for critically ill patients. In patients receiving adequate energy, optimal protein- sparing effects are achieved when proteins are administered at rates between 1.3 and 1.5 g/kg/day [54]. The low protein delivery in both groups may have resulted to a non- difference in mechanical ventilation days. Aggressive provision of proteins particularly during the acute and chronic phase of critical illness could have resulted to significant positive outcomes. Our study population composed of a heterogeneous group of patients (mixed medical- surgical) and therefore would have variable pathophysiological consequences. Nutrition therapy will not be the only factor that will affect clinical outcomes. Severity of disease upon admission, the course of the disease process, the medical/surgical management, and the individual patient response to management will determine prognosis and clinical outcomes. One of the limitations of the study includes the retrospective- observational nature of the design with relatively small sample size. The latter affects power of the test decreasing the chance of getting significant results. Since nutritional data in our study was taken only within the first seven ICU days, the mean percent adequacy in our study was lower as compared to most guidelines on ICU patients. There was no available portable indirect calorimeter so that energy requirements of the patient were determined using the predictive method, which has accuracy between 37% and 65% only [51]. There is lack of full implementation of feeding protocols and monitoring particularly among patients not referred to the nutrition team. St. Luke s Medical Center is a private tertiary hospital, that s why length of ICU stay and hospital stay can also be influenced with the patient and/or family member s desire or request to be discharged earlier or much later. CONCLUSION: Critically ill patients will have improved survival with adequate calorie and protein intake. Outcomes would be even more significant when nutrient delivery is optimal according to current guidelines. Since patients referred to the clinical nutrition team achieved higher calorie and protein intake, survival appears to be better among patients referred to the nutrition team. REFERENCES: 1. Villet S, Chiolero RL, Bollmann MD, Revelly JP, Cayeux RNM, Delarue J, Berger MM: Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patients. Clin Nutr 2005, 24: Barr J, Hecht M, Flavin KE, Khorana A & Gould MK (2004) Outcomes in critically ill patients before and after the implementation of an evidence- based nutritional management protocol. Chest 125; Dvir D, Cohen J, Singer P: Computerized energy balance and complications in critically ill patients: an observational study. Clin Nutr 2006; 25: Martin C, Doig G, Heyland D, Morrison T, Sibbald W: Multicentre, cluster- randomized clinical trial of algorithms for critical- care enteral and parenteral therapy (ACCEPT) CMAJ 2004; 170(2): Faisy C, Lerolle N, Dachraoui F, et al. Impact of energy deficit calculated by a predictive method on outcome in medical patients requiring prolonged acute mechanical ventilation. Br J Nutr 2009; 101:

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