Background: The optimal rate of feeding advancement after initiation of early enteral nutrition (EEN) for underweight, critically ill patients is unknown. Methods: We conducted a retrospective chart review in intensive care unit (ICU) patients with a body mass index (BMI) < 20.0 kg/m 2. Patients were categorized into Group R, which reached the energy target within 3 days of EEN initiation, and Group S, which reached the energy target 4 or more days after EEN initiation. Results: A total of 65 patients with a median age of 73 years were included in the study. No significant differences were observed between the two groups for all-cause mortality, ICU-free days, or length of hospital stay. Ventilator-free days (VFDs) were significantly fewer in Group R than in Group S (18.0 [0.0 - 22.0] vs. 21.0 [16.3 - 24.8] days; P = 0.046). A significantly higher number of patients requiring mechanical ventilation (MV) at hospital discharge were observed in Group R than in Group S (29% vs. 8%; P = 0.030). Multivariable analyses with adjustment for confounders found that days required to reach target energy intake after EEN initiation were significantly and independently associated with the requirement for MV at hospital discharge, but not with VFDs. Conclusion: A slow rate of feeding advancement after initiation of EEN in critically ill patients having a BMI of <20.0 kg/m 2 might be associated with a reduced requirement for MV at hospital discharge. These results require confirmation in a large multicenter trial of underweight, critically ill patients.
Nutritional support is essential for the management of intensive care unit (ICU) patients. Enteral nutrition (EN) is the preferred route for nutritional support in critically ill patients [
Following the initiation of EEN, clinical guidelines recommend that feeding be advanced toward a goal rate over the next 48 - 72 h [
Here, to examine the impact of feeding advancement rate after the initiation of EEN on the mortality and morbidity of underweight and critically ill patients, we performed a retrospective chart review of patients with a body mass index (BMI) < 20.0 kg/m2.
This single-center retrospective chart review was conducted in an 8-bed emergency intensive care unit (EICU) of a tertiary teaching hospital. The EICU is an emergency admission ward in which patients with serious emergency medical or surgical conditions receive intensive care. Critically ill patients transferred from general wards or following elective surgery are admitted to other ICUs. The study received approval from the ethics committee of the study institution. Owing to the nature of the study, the requirement for informed patient consent was waived.
Consecutive patients admitted to the EICU from August 2011 to July 2014 were screened for eligibility. If the patients in our previous study met the inclusion criteria below, they were also included in the present study, as the two study periods overlapped (Aug 2011-Dec 2012) [
Data were obtained from the medical records of patients. The following baseline demographic characteristics were recorded: age, sex, body weight and height on admission, and BMI. BMI was calculated based on weight (kg)/height (m2) on admission. The following baseline clinical characteristics were recorded: Acute Physiology and Chronic Health Evaluation (APACHE) II Score (which ranges from 0 to 71, with higher scores indicating more severe illness) [
An energy target of 25 kcal/kg/day was set as the required energy for the majority of critically ill patients [
Clinical outcomes in Groups R and S were compared. The following variables were analyzed:
1) All-cause mortality in the hospital and EICU.
2) ICU-free days and length of hospital stay. ICU-free days were defined as the number of days between successful transfer to a general ward and Day 28 after EICU admission. ICU-free days were 0 if the patient died before Day 28 or stayed in the EICU or other ICUs for ≥28 days. For the length of hospital stay, patients who died during hospitalization were excluded from the analysis.
3) Ventilator-free days (VFDs). VFDs were defined as the number of days between successful weaning from MV and Day 28 after EICU admission. VFDs were 0 if the patient died before Day 28 or required MV for ≥28 days.
4) Number of patients requiring continuous or intermittent MV via tracheostomy at hospital discharge. The decision of when to wean from MV was made following discussion among the attending and/or EICU physicians.
5) Number of patients undergoing tracheostomy in the EICU or hospital. The decision of when to perform a tracheostomy was made following discussion among the attending and/or EICU physicians.
6) Antibiotic-free days as the number of days during the 28 days after living patients had been admitted to the EICU and had not received any antibiotics as treatment for infections or as prophylaxis.
7) Inflammatory index, as maximum plasma C-reactive protein (CRP) level during the first 28 days after EICU admission.
8) Number of patients clinically diagnosed with pneumonia by EICU physicians during the first 28 days after EICU admission, and number of patients who developed ventilator-associated pneumonia (VAP) [
9) Number of patients exhibiting liver dysfunction, defined as a total bilirubin level of >1.2 mg/dL during the first 28 days after EICU admission.
10) Number of patients exhibiting renal dysfunction, as determined by an increase in serum creatinine level of >1.2 mg/dL or need for renal replacement therapy during the first 28 days after EICU admission.
11) Number of patients exhibiting hypoglycemia, defined as a blood glucose level of <70 mg/dL [
12) Number of patients receiving insulin therapy and average daily insulin dose in the first week and 28 days after EICU admission. Target glucose level was set as 100 to 180 mg/dL.
13) Number of patients exhibiting hypophosphatemia, defined as a serum phosphorus (P) concentration < 2.7 mg/d [
Data for continuous variables are presented as median and inter quartile range and for categorical variables as numbers and percentages. Groups were compared using the Mann-Whitney U test (continuous data) and Fisher’s exact test (categorical data). We used the nonparametric test for continuous variables as the relatively small sample size underestimated the distribution assumptions for parametric tests. Multiple regression and multiple logistic regression analyses were conducted with VFDs and the requirement for MV at hospital discharge as the dependent variables; and days to reach target energy intake from EEN initiation, initial SOFA score, admission source, category of admission, and time to EEN initiation from EICU admission as independent variables. Multivariable analyses were conducted to identify the impact of days to reach target energy intake from EEN initiation on outcomes following control for differences in patients’ baseline characteristic. Statistical analyses were conducted using SPSS statistical software v. 21 (IBM, Armonk, NY, USA). P values < 0.05 were considered significant.
Among the 1993 patients who were assessed for eligibility, 65 met the criteria and were included in the study (
Initiation of EN for patients in Group R was earlier than in Group S (14.5 [4.7 - 21.9]
vs. 24.7 [12.6 - 36.4] h; P = 0.010). Median time to reach target energy intake from EEN initiation was 2 days in Group R and 5 days in Group S. Energy and protein intakes in the first week of EICU admission were higher in Group R than in Group S (24.6 [22.1 - 28.1] vs. 17.7 [13.6 - 20.4] kcal/kg BW/day; P < 0.001, 1.1 [0.9 - 1.3] vs. 0.7 [0.5 - 0.9] g; P < 0.001, respectively).
Characteristic | Group R | Group S | |
---|---|---|---|
Rapid EN advancement | Slow EN advancement | P value | |
N = 41 | N = 24 | ||
Demographic | |||
Age, years; median (IQR) | 72.8 (64.1 - 83.0) | 73.6 (61.9 - 81.0) | 0.563 |
Sex | 0.135 | ||
Female, n (%) | 22 (54) | 17 (71) | |
Male, n (%) | 19 (46) | 7 (29) | |
Height, cm; median (IQR) | 160.0 (153.0 - 170.0) | 162.5 (154.3 - 170.0) | 0.801 |
Weight, kg; median (IQR) | 46.5 (41.5 - 53.4) | 45.0 (41.9 - 49.5) | 0.719 |
BMI, kg/m2; median (IQR) | 18.2 (16.4 - 19.2) | 17.7 (16.1 - 19.1) | 0.634 |
Clinical characteristic | |||
APACHE II score (IQR) | 21.0 (18.5 - 31.5) | 22.0 (19.0 - 27.5) | 0.563 |
Initial SOFA score (IQR) | 10.0 (9.0 - 13.0) | 9.0 (8.0 - 10.0) | 0.029 |
Admission category, n (%) | 0.001 | ||
Medical | 28 (68) | 6 (25) | |
Surgical | 13 (32) | 18 (75) | |
Source of admission | 0.007 | ||
Emergency department | 21 (51) | 12 (50) | |
Emergency ward | 7 (17) | 1 (4) | |
Operating room | 6 (15) | 11 (46) | |
Other hospital | 7 (17) | 0 (0) | |
Primary EICU diagnosis, n (%) | 0.052 | ||
Cardiovascular or vascular disorder | 6 (15) | 1 (4) | |
Respiratory disorder | 7 (17) | 3 (13) | |
Gastrointestinal disorder | 0 (0) | 0 (0) | |
Neurologic disorder | 18 (44) | 15 (63) | |
Sepsis | 6 (15) | 0 (0) | |
Trauma | 0 (0) | 3 (13) | |
Metabolic disorder | 2 (5) | 2 (8) | |
Burn | 1 (2) | 0 (0) | |
Renal disorder | 1 (2) | 0 (0) | |
Comorbidity | |||
Charlson comorbidity index; median (IQR) | 5.0 (3.5 - 6.0) | 5.0 (3.0 - 5.0) | 0.234 |
Diabetes mellitus, n (%) | 4 (10) | 1 (4) | 0.385 |
Dialysis dependent renal failure, n (%) | 3 (7) | 0 (0) | 0.244 |
Chronic obstructive pulmonary disease, n (%) | 3 (7) | 2 (8) | 0.615 |
Cardiac disease, n (%) | 8 (20) | 2 (8) | 0.201 |
Anemia (hemoglobin < 8.0 g/dl on EICU admission), n (%) | 3 (7) | 1 (4) | 0.527 |
---|---|---|---|
Nutritional characteristic | |||
Time to initiation of EEN from EICU admission, h; median (IQR) | 14.5 (4.7 - 21.9) | 24.7 (12.6 - 36.4) | 0.010 |
Days to reach target energy intake from EEN initiation, day; median (IQR) | 2.0 (2.0 - 3.0) | 5.0 (4.0 - 7.0) | <0.001 |
Average energy intake during first week in EICU, kcal/kg/day; median (IQR) | 24.6 (22.1 - 28.1) | 17.7 (13.6 - 20.4) | <0.001 |
Average protein intake during first week in EICU, g/kg/day; median (IQR) | 1.1 (0.9 - 1.3) | 0.7 (0.5 - 0.9) | <0.001 |
Data were provided as median and interquartile range for continuous variables and as number and percentage for categorical variables. Mann-Whitney U test was used for continuous data and Fisher’s exact test for categorical data. Group R reached 25 kcal/kg/day within 3 days of EEN initiation; Group S reached 25 kcal/kg/day 4 or more days after EEN initiation. Energy intake included intake via enteral and parenteral routes; glucose infusions used for fluid support, drug dilution and correction of hypoglycemia; and lipids delivered with sedatives (e.g., propofol). Either oral or parenteral nutrition was not initiated within the first week of EICU admission. APACHE II = The Acute Physiology and Chronic Health Evaluation II, EEN = early enteral nutrition, EICU = emergency intensive care unit, EN = enteral nutrition, IQR = interquartile range, SOFA = Sequential Organ Failure Assessment.
concentrations, or dose of P required for the treatment of hypophosphatemia.
Because VFDs might have been influenced by factors other than the rate of feeding advancement that were analyzed in our study, we also conducted a multiple regression analysis with VFDs as the dependent variable, using days to reach target energy intake from EEN initiation, initial SOFA score, category of admission, admission source and time to initiation of EEN from EICU admission as independent variables. Results showed no independent correlation between the number of days to reach target energy intake from EEN initiation and VFDs (regression coefficient = 0.500; 95% confidence interval, −0.420 - 1.419).
In a similar manner, a multiple logistic regression analysis was also conducted to assess the independent effect of days to reach target energy intake from EEN initiation on the requirement for MV at hospital discharge after controlling for other factors, namely days to reach target energy intake from EEN initiation, initial SOFA score, category of admission, source of admission and time to initiation of EEN from EICU admission. Days to reach target energy intake from EEN initiation was significantly and independently associated with the requirement for MV at hospital discharge (
In this study, we found no significant differences in the all-cause mortality or number of ICU- and length of hospital stay between patients with BMI < 20.0 kg/m2 who received a rapid or slow rate of feeding advancement after initiation of EEN in the EICU. However, VFDs were significantly lower and the requirement for MV at hospital discharge
Outcome | Group R | Group S | |
---|---|---|---|
Rapid EN advancement | Slow EN advancement | P value | |
n=41 | n=24 | ||
All-cause mortality | |||
In EICU, n (%) | 0 (0) | 0 (0) | 1.000 |
In hospital, n (%) | 3 (7) | 0 (0) | 0.244 |
Length of stay | |||
ICU-free days, days; median (IQR) | 19.0 (13.5 - 22.0) | 20.5 (15.3 - 23.0) | 0.309 |
Length of hospital stay, days; median (IQR) | 38.3 (29.1 - 54.1) | 50.4 (35.7 - 61.2) | 0.128 |
Mechanical ventilation | |||
Mechanical ventilation-free days, days; median (IQR) | 18.0 (0.0 - 22.0) | 21.0 (16.3 - 24.8) | 0.046 |
Requirement for mechanical ventilation at hospital discharge, n (%) | 12 (29) | 2 (8) | 0.030 |
Tracheostomy, n (%) | |||
In EICU | 18 (44) | 12 (50) | 0.448 |
In hospital | 26 (63) | 17 (71) | 0.422 |
Antibiotic-free days, days; median (IQR) | 15.0 (8.5 - 19.0) | 12.5 (8.0 - 18.8) | 0.410 |
Highest CRP, mg/dl; median (IQR) | 16.0 (9.6 - 22.9) | 16.2 (8.3 - 21.6) | 0.703 |
Pneumonia | |||
Clinical diagnosis of pneumonia, n (%) | 16 (39) | 9 (38) | 0.559 |
Development of VAP, n (%) | 1 (2) | 0 (0) | 0.631 |
Liver and kidney dysfunction | |||
Liver dysfunction (serum bilirubin > 1.2 mg/dl), n (%) | 9 (22) | 6 (25) | 0.503 |
Renal dysfunction (serum creatinine > 1.2 mg/dl) or requirement for RRT, n (%) | 16 (39) | 4 (17) | 0.052 |
Glycemic control | |||
Hypoglycemia (<70 mg/dl) free days, days; median (IQR) | 28.0 (26.5 - 28.0) | 28.0 (27.0 - 28.0) | 0.539 |
Received insulin administration, n (%) | |||
First week in EICU | 19 (46) | 6 (25) | 0.073 |
During 28 days after EICU admission | 22 (54) | 8 (33) | 0.092 |
Average insulin daily dose (units) | |||
First week in EICU | 7.8 (2.7 - 16.8) | 4.8 (1.6 - 26.3) | 0.775 |
During 28 days after EICU admission | 2.5 (0.6 - 11.0) | 1.2 (0.4 - 20.6) | 0.386 |
Electrolytes | |||
Hypophosphatemia (<2.7 mg/dl), n (%) | |||
First week in EICU | 18 (44) | 8 (33) | 0.193 |
During 28 days after EICU admission | 22 (54) | 8 (33) | 0.400 |
Lowest serum P concentrations, mg/dl; median (IQR) | |||
---|---|---|---|
First week in EICU | 2.4 (1.7 - 3.2) | 2.1 (2.0 - 2.5) | 0.277 |
During 28 days after EICU admission | 2.4 (1.8 - 3.0) | 2.2 (1.9 - 2.5) | 0.399 |
Dose of P to treat hypophosphataemia, mmol/day; median (IQR) | |||
First week in EICU | 0 (0 - 0) | 0 (0 - 0) | 0.846 |
During 28 days after EICU admission | 0 (0 - 0) | 0 (0 - 0) | 0.808 |
Data were provided as median and interquartile range for continuous variables and as number and percentage for categorical variables. Mann-Whitney U test was used for continuous data and Fisher’s exact test for categorical data. Group R reached 25 kcal/kg/day within 3 days of EEN initiation; Group S reached 25 kcal/kg/day 4 or more days after EEN initiation. Energy intake included intake via enteral and parenteral routes; glucose infusions used for fluid support, drug dilution and correction of hypoglycemia; and lipids delivered with sedatives (e.g., propofol). Either oral or parenteral nutrition was not initiated within the first week of EICU admission. CRP = C-reactive protein, EEN = early enteral nutrition, EICU = emergency intensive care unit, EN = enteral nutrition, ICU = intensive care unit, IQR = interquartile range, P = phosphorus, RRT = renal replacement therapy, VAP = ventilator associated pneumonia.
Independent variable | Adjusted OR (95% CI) | P value |
---|---|---|
Days to reach target energy intake from EEN initiation† | 0.467 (0.245 - 0.889) | 0.020 |
Initial SOFA | 1.324 (0.990 - 1.769) | 0.058 |
Admission category, medical/surgical | 0.458 (0.064 - 3.287) | 0.438 |
Source of admission | ||
Emergency department | 1 (reference) | |
Emergency ward | 1.613 (0.159 - 16.33) | 0.686 |
Operating room | 0.243 (0.011 - 5.282) | 0.368 |
Other hospital | 1.656 (0.064 - 43.11) | 0.762 |
Time to initiation of EEN from EICU admission | 1.015 (0.949 - 1.086) | 0.657 |
†Energy target was set at 25 kcal/kg/day for all patients. Energy intake included intake via enteral and parenteral routes; glucose infusions used for fluid support, drug dilution and correction of hypoglycemia; and lipids delivered with sedatives (e.g., propofol). Either oral or parenteral nutrition was not initiated within the first week of EICU admission. CI = confidence interval, EEN = early enteral nutrition, EICU = emergency intensive care unit, SOFA = Sequential Organ Failure Assessment.
was significantly higher in those with rapid feeding advancement. Multivariable analyses with adjustment for confounders revealed that the number of days to reach target energy intake from EEN initiation was significantly and independently associated with the requirement for MV at hospital discharge, but not with the VFDs.
In our previous study, we only focused on mean daily energy intake during the first week of EICU admission [
To our knowledge, this study is the first to evaluate the influence of the rate of feeding advancement after initiation of EEN on mortality and morbidity in underweight and critically ill and patients during emergency admission. Guidelines for critical care from the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) recommend the advancement of feeding toward the target over the 48 - 72 h after the start of EEN [
In contrast, several other studies do not support a rapid rate of feeding advancement for critically ill patients. Arabi et al. studied enterally-fed patients with a mean BMI of approximately 29 kg/m2 and reported that underfeeding during the ICU stay (energy target: 60% - 70% of calculated requirement) was associated with lower mortality than target feeding [
Most of the above studies were performed in patients aged from 50 to 70 years with a BMI of >25 kg/m2. In contrast, the patients in the present study had a BMI of <20.0 kg/m2 and were older with median age of 73 years. These patients were admitted to the EICU to receive emergency medical or surgical treatment, while patients from general wards or were post-elective surgery were excluded. Low BMI is associated with higher complications and mortality in ICU as well as non-ICU settings [
In our evaluation of the influence of rapid or slow feeding advancement after initiation of EEN on mortality and morbidity in critically ill medical and surgical patients with a BMI of <20 kg/m2, we observed that a slow advancement rate was associated with a lower requirement for MV at hospital discharge. However, the reliability of this result is statistically limited. Normally, multiple logistic regression analysis requires at least ten outcomes for one independent variable. Unfortunately, we were unable to adopt this method due to our small sample size. Several potential mechanisms might explain the association of rapid feeding advancement with an increased requirement for MV at hospital discharge. Increased feeding might have resulted in EN-related complications, for example aspiration pneumonia [
Several limitations of the present study warrant mention. First and most importantly, sample size was small, and the study was conducted at a single institution. Further, study subjects were old Japanese with median age of 73 years. Our results are therefore limited and require confirmation in a larger sample size in patients with different generational and ethnic backgrounds. Second, the study was conducted under a retrospective design and groups were not randomized, which might have resulted in a degree of bias. Third, nutritional status was defined by BMI alone, which might be unreliable for nutritional assessment as actual body weight early in the clinical course might be influenced by non-nutrition factors such as fluid balance and inflammatory status. Further, we were unable to determine whether patients developed illness-related weight loss or were healthy despite their low body weight prior to EICU admission. Finally, an energy target was set at 25 kcal/kg/day for all patients, which was not tailored to the clinical status of each patient. In addition, the reason why physicians advanced EN rapider in Group R could not be identified. Thus, a conclusive answer to whether a slow rate of feeding advancement after the initiation of EEN improves outcomes in critically ill underweight patients requires large multicenter prospective studies with random patient assignment.
The results of this single-center, retrospective chart analysis demonstrate that a slow rate of feeding advancement after initiation of EEN in critically ill patients having a BMI of <20.0 kg/m2 might be associated with a reduced requirement for MV at hospital discharge. These results require confirmation in a large multicenter trial which enrolls underweight and critically ill patients.
The authors thank the EICU staff for their support, collection of data, and review of this manuscript.
Ichimaru, S., Sono, M., Fujiwara, H., Seo, R. and Ariyoshi, K. (2016) The Impact of Rate of Feeding Advancement after Early Initiation of Enteral Nutrition in Critically Ill, Underweight Pa- tients: A Single-Center Retrospective Chart Review. Food and Nutrition Sciences, 7, 939-954. http://dx.doi.org/10.4236/fns.2016.711093