Abstract
Objective
To analyze the influencing factors and nursing strategies for enteral nutrition patients complicated with refeeding syndrome (RS) in the ICU.
Methods
A total of 173 enteral nutrition patients in the ICU admitted to our hospital from January 2020 to January 2021 were retrospectively analyzed. Patients were divided into a control group (without RS, n = 128) and an observation group (with RS, n = 45) based on whether they developed RS. The general data such as gender, age, and body mass index (BMI) of patients were compared. The enteral nutrition-related indexes of two groups such as gastrointestinal decompression before feeding, diuretic application before feeding, and parenteral nutrition were compared. The risk factors of RS in ICU enteral nutrition patients were analyzed by multivariate logistic regression. Patients in the observation group received targeted nursing strategies according to the risk factors. The levels of serum phosphorus, potassium, magnesium, albumin, and prealbumin were detected before and after nursing intervention.
Results
The proportion of age ≥ 60 years, BMI ≥ 18.5 kg/m2, diabetes history, cerebrovascular disease, severe pneumonia, acute physiology and chronic health evaluation (APACHE) II score > 20, duration of mechanical ventilation ≥ 3 days, NRS 2002 rating high risk in the observation group was much higher than that in the control group (P < 0.05). The observation group had a much higher proportion of whole protein nutrient solution, nasoenteric tube feeding, protein intake ≥ 1.2 g/kg, feeding speed > 50 ml/h, and enteral nutrition temperature 36–38℃ than the control group (P < 0.05). Multivariate logistic regression analysis pointed out that age ≥ 60 years, NRS 2002 score > 5, duration of mechanical ventilation ≥ 3 days, APACHE II score > 20, feeding speed > 50 ml/h, protein intake ≥ 1.2 g/kg, and enteral nutrition temperature 36–38℃ were independent risk factors of enteral nutrition patients complicated with RS in ICU (P < 0.05). After the intervention of targeted nursing strategies, the serum levels of phosphorus, potassium, magnesium, albumin, and prealbumin were obviously elevated than before (P < 0.05).
Conclusion
Age, NRS 2002 score, mechanical ventilation time, APACHE II score, feeding speed, protein intake, and enteral nutrition temperature are all risk factors of refeeding syndrome in ICU enteral nutrition patients. Targeted nursing intervention according to the influencing factors can effectively improve the efficacy of enteral nutrition and reduce or prevent other complications.
Keywords: Enteral nutrition in ICU, Refeeding syndrome, Influencing factors, Nursing countermeasures
Introduction
Refeeding syndrome (RS) is a potentially fatal nutritional therapy syndrome, which is defined as a clinical syndrome in which patients with hunger or malnutrition are given artificial feeding with normal nutritional requirements, and often present with multiple systemic symptoms such as electrolyte disorders, respiratory and circulatory systems [1]– [2]. RS is commonly seen in patients receiving enteral nutrition in the ICU and could be accompanied by symptoms such as respiratory failure, heart failure, pulmonary edema, etc. In severe cases, RS can lead to death [3]. According to the statistics of relevant studies [4]– [5], the incidence of RS in ICU patients with enteral nutrition fluctuated within a certain range, roughly between 10% and 30%.
The pathological mechanism of RS is complex. When hunger or malnutrition occurs, the body decomposes, and intracellular electrolytes (phosphorus, potassium, magnesium, etc.) are released to the outside of the cell. After refeeding, especially after rapid intake of macronutrients, the insulin level increases, which enhances the cellular uptake of electrolytes (potassium, magnesium, phosphate, etc.), leading to a sharp decline in extracellular electrolyte concentration and electrolyte disorders such as hypophosphatemia [6]. At the same time, anabolic metabolism accelerates the consumption of large amounts of vitamins (such as thiamine). If the supplement is not timely, it will aggravate metabolic disorders, affect cell function, and cause multi-system dysfunction, which can lead to death in severe cases. In this process, the obstacle of rapid transformation from catabolism to anabolism is the key link [7]. In the ICU environment, on the one hand, critically ill patients are in a serious condition, often accompanied by multiple organ dysfunction, and gastrointestinal dysfunction may lead to malabsorption of nutrients, making patients more likely to have abnormal nutrient metabolism in the process of enteral nutrition, thereby increasing the risk of refeeding syndrome [8]. On the other hand, ICU patients often need to be treated with a variety of drugs. Diuretics may cause electrolyte loss, further perturb the electrolyte balance in the body, and are more likely to induce RS during enteral nutrition [9]. These factors make ICU patients a high-risk group for RS and need special attention.
With the increase in the proportion of the elderly in recent years, the number of patients with RS is also increasing year by year. The study [10] shows that the mortality rate of patients receiving enteral nutrition in ICU can be as high as 10-50%, which not only increases the pain of patients and affects the treatment effect of patients, but also increases the economic burden of families and society. Relevant data confirms [11] that RS patients lack clinically specific symptoms. Due to the critical condition of ICU patients, medical staff have insufficient understanding and prevention of their condition, resulting in an incomplete evaluation system for related influencing factors. The incidence rate and mortality of severe patients with RS can be reduced through risk assessment of RS patients, formulation of nutrition care plans, and monitoring. Therefore, early analysis of RS-related influencing factors in ICU enteral nutrition patients and providing nursing strategies based on the influencing factors may help reduce the incidence of RS and is of great significance for improving treatment effectiveness and patient prognosis.
In this study, the clinical data of 173 enteral nutrition patients in ICU admitted to our hospital from January 2020 to January 2021 were retrospectively analyzed. We aimed to analyze the influencing factors and nursing strategies of concurrent RS in ICU enteral nutrition patients and provide reference experience for clinical application.
Materials and methods
General materials
This study was a single-center retrospective cohort analysis, and 173 enteral nutrition patients in the ICU admitted to our hospital from January 2020 to January 2021 were retrospectively analyzed. Inclusion criteria: (1) The patient was admitted to the ICU for the first time and received enteral nutrition within the ICU for ≥ 72 h; (2) The patient and their family members were informed and had good compliance. They could cooperate with examinations and treatment, and all signed informed consent forms; (3) The patient was ≥ 18 years old. Exclusion criteria: (1) patients with incomplete clinical data; (2) The patient during lactating or pregnant period; (3) The patient accompanied by sustained hemodialysis and thyroidectomy which could lead to hypophosphatemia. Patients were divided into a control group (without RS, n = 128) and an observation group (with RS, n = 45) based on whether they developed RS. Diagnostic criteria for RS are as follows [12]: (1) Mild RS: a 10–20% decrease in phosphorus, potassium, or magnesium levels; (2) Moderate RS: a 20-30% decrease in phosphorus, potassium, or magnesium levels; (3) Severe RS: a > 30% decrease in phosphorus, potassium, magnesium and/or organ dysfunction due to decreased electrolyte levels or vitamin B1 (thiamine) deficiency. RS was diagnosed when any of these three factors were present and occurred within 5 days after the resumption of feeding or a large increase in energy supply. All patients’ serum levels of phosphorus, potassium, and magnesium were monitored daily after enrollment. Two senior attending physicians independently evaluated whether RS occurred and its severity based on the above criteria. When the assessment results are inconsistent, the third associate chief physician shall arbitrate and confirm. All experimental operations were approved by the Ethics Committee of our hospital. Written informed consent to participate was obtained from all of the participants in the study. Flow chart of general information selection was shown in Fig. 1.
Fig. 1.
Flow chart of general information selection
Nursing strategies
Patients in the control group received routine enteral nutrition nursing intervention: Enteral nutrition was provided to patients admitted to the ICU who were unable to eat orally. The types of enteral nutrition mainly included whole protein and short peptides. The energy supply of enteral nutrition mainly comes from carbohydrates, lipids, and proteins. Among them, carbohydrates mainly exist in the form of glucose polymers and other forms, accounting for about 50-60% of the total energy. Lipids were mainly medium and long-chain fatty acids, accounting for about 20-30% of the total energy. In terms of mineral supplementation, according to the basic condition and nutritional needs of patients, the supplement of various minerals was adjusted, with the daily supplement of phosphorus 1.0–2.0 mmol, potassium 2.0–4.0 mmol, magnesium 0.5–1.5 mmol, etc. In addition, for different patients, the proportion and formula of enteral nutrition components were adjusted according to the patient’s digestive and absorption capacity, disease status, and other factors, so as to ensure the rationality and effectiveness of the patient’s nutritional intake.
Nasogastric tubes or nasointestinal tubes were chosen based on the patient’s condition and the wishes of their families. After placement of the tube, the nasogastric or nasointestinal tube was positioned in place ensured by the following methods: X-ray examination was used to confirm whether the catheter reached the correct position by observing its position in the body. It could also be judged by extracting gastric contents or intestinal fluid. If the gastric or intestinal fluid was extracted, the position of the catheter might be correct. The pH value detection method could also be used to assist in determining the position of the catheter by detecting the pH value of the extracted fluid. For example, the pH value of the gastric fluid was usually acidic, while the pH value of the intestinal fluid was relatively high. The sterile nutrient solution was continuously infused with a nutrient pump for 12–24 h, with an initial infusion rate of 30 ml/h. The infusion speed gradually increased according to the patient’s tolerance, with a maximum of 120 ml/h. Routine enteral nutrition care is a standard operation for ICU patients [13].
Based on the control group, the observation group was given targeted nursing strategies based on the influencing factors of enteral nutrition patients complicated with RS in ICU: (1) Learn about whether there were risk factors for concurrent RS in patients through family members. Patients with risk factors were given special attention to changes in their condition. (2) Electrolytes were checked before enteral nutrition, and the frequency of check and correction was determined according to the patient’s condition. Patients with stable conditions and mild disorders should be checked every 24 to 48 h. Severe or fluctuating cases should be checked every 12–24 h. According to the principle of “fill what is missing, fill how much is missing”, oral or intravenous infusion of electrolyte solution, such as potassium phosphate/sodium for hypophosphatemia, potassium chloride for hypokalemia was used for the correction, and monitoring electrocardiogram and blood potassium were monitored to prevent hyperkalemia. (3) The caloric intake of patients was calculated and the enteral nutrition program was customized. According to age, sex, weight, height, disease status, and metabolic level, the Harris-Benedict formula was used to calculate basic energy expenditure and then adjusted with the amount of activity and stress state. For diabetic patients, the proportion of carbohydrates was reduced, the dietary fiber was increased, and the dosage of insulin or antidiabetic drugs was adjusted according to blood glucose monitoring. For patients with liver and kidney insufficiency, the intake and type of protein should be adjusted according to the indicators, high-quality protein should be selected, and the changes in liver and kidney function should be paid attention to. (4) The weight of the patient was measured once a day, and the weight gain of 0.45–0.90 kg in 1 week indicated fluid retention. The signs evaluated included edema of the lower limbs (when the skin in front of the tibia was pressed, there was edema if the depression was slowly recovered), pulmonary rales (auscultation of the lungs, wet rales suggested pulmonary edema), and jugular vein filling (observation of whether it was irritated to determine venous pressure). If fluid retention occurred, fluid was limited and treated with diuretics (such as furosemide) according to the situation, and electrolytes were monitored to prevent disturbances. (5) Blood glucose was measured every 4–6 h, depending on the condition, with a target fasting blood glucose of 7–10 mmol/L and 8–12 mmol/L 2 h after a meal. If blood glucose is high, the carbohydrate infusion rate should be reduced or the insulin dosage should be increased. For patients with low blood glucose, carbohydrate intake was increased or insulin dosage was reduced, and the symptoms of hypoglycemia (palpitation, shaking hands, sweating) were observed.
Outcome measures
General data: The general data of patients were compared, including gender, age, body mass index (BMI), diabetes history, cerebrovascular disease, drinking history, smoking history, severe pneumonia, acute physiology, and chronic health valuation II (APACHE II), nutritional risk screening 2002 (NRS-2002), and duration of mechanical ventilation.
Enteral nutrition-related indicators: The enteral nutrition-related indicators of patients were compared, including gastrointestinal decompression before feeding, diuretic application before feeding, parenteral nutrition, nutrient solution type, feeding route, protein intake, feeding speed, and enteral nutrition temperature. At the same time, the daily energy intake (including the energy value provided by carbohydrates and lipids) and the specific types and intake of minerals were recorded in detail during the period of enteral nutrition, and the relationship between these factors and the occurrence of refeeding syndrome was analyzed.
Nursing intervention effect: The levels of serum phosphorus, potassium, magnesium, albumin, and prealbumin in the observation group before and after nursing intervention were compared. Before the nursing intervention, blood samples were collected once when patients were admitted to the ICU and confirmed to receive enteral nutrition support to detect the basic levels of the above indicators. Blood samples were collected again one day before the patients were transferred out of the ICU to detect the above indicators, and the continuous effect of nursing intervention on the nutritional status of patients during the whole ICU hospitalization was evaluated.
Statistical analysis
The experimental data was analyzed using SPSS 20.0 software. The measurement data that conformed to the normal distribution were represented by (‾x ± s). The inter-group comparison was conducted using a t-test, and the comparison before and after treatment in the same group was conducted with the paired t-test. Age, BMI, diabetes history, cerebrovascular disease, severe pneumonia, APACHE II score, duration of mechanical ventilation, and other enumeration data were shown as (%) and compared using the χ2 test. Multiple logistic regression analysis was used to investigate the influencing factors of RS in ICU patients with enteral nutrition. The statistically significant results were those with P < 0.05.
Results
Comparison of clinical data
The proportion of age ≥ 60 years, BMI ≥ 18.5 kg/m2, diabetes history, cerebrovascular disease, severe pneumonia, acute physiology and chronic health evaluation (APACHE) II score > 20, duration of mechanical ventilation ≥ 3 days, NRS 2002 score > 5 in the observation group was much higher than that in the control group (P < 0.05, Table 1).
Table 1.
Comparison of clinical data (cases, %)
| Index | The control group (n = 128) | The observation group (n = 45) | χ2 | P | |
|---|---|---|---|---|---|
| Gender | Male | 74 (57.81%) | 31 (68.89%) | 1.712 | 0.191 |
| Female | 54 (42.19%) | 14 (31.11%) | |||
| Age | < 60 | 68 (53.12%) | 15 (33.33%) | 5.225 | 0.022 |
| ≥ 60 | 60 (46.88%) | 30 (66.67%) | |||
| BMI | < 18.5 kg/m2 | 20 (15.63%) | 17 (37.78%) | 9.718 | 0.002 |
| ≥ 18.5 kg/m2 | 108 (84.37%) | 28 (62.22%) | |||
| Diabetes history | Yes | 30 (23.44%) | 19 (42.22%) | 5.787 | 0.016 |
| No | 98 (76.56%) | 26 (57.78%) | |||
| Cerebrovascular disease | Yes | 9 (7.03%) | 8 (17.78%) | 4.339 | 0.037 |
| No | 119 (92.97%) | 37 (82.22%) | |||
| Drinking history | Yes | 26 (20.31%) | 8 (17.78%) | 0.136 | 0.713 |
| No | 102 (79.69%) | 37 (82.22%) | |||
| Smoking history | Yes | 31 (24.22%) | 11 (24.44%) | 0.001 | 0.976 |
| No | 97 (75.78%) | 34 (75.56%) | |||
| Severe pneumonia | Yes | 16 (12.50%) | 12 (26.67%) | 4.926 | 0.026 |
| No | 112 (87.50%) | 33 (73.33%) | |||
| APACHE II score | < 10 | 26 (20.31%) | 11 (24.44%) | 8.906 | 0.012 |
| 10–20 | 71 (55.47%) | 14 (31.11%) | |||
| > 20 | 31 (24.22%) | 20 (44.44%) | |||
| Duration of mechanical ventilation | < 3d | 38 (29.69%) | 23 (51.11%) | 6.694 | 0.010 |
| ≥ 3d | 90 (70.31%) | 22 (48.89%) | |||
| NRS 2002 score | < 3 | 66 (51.56%) | 6 (13.33%) | 35.326 | < 0.001 |
| 3–5 | 52 (40.63%) | 20 (44.44%) | |||
| > 5 | 10 (7.81%) | 19 (42.22%) | |||
Comparison of enteral nutrition-related indicators
The observation group had a much higher proportion of whole protein nutrient solution, nasoenteric tube feeding, protein intake ≥ 1.2 g/kg, feeding speed > 50 ml/h, and enteral nutrition temperature 36–38℃ than the control group (P < 0.05, Table 2).
Table 2.
Comparison of enteral nutrition-related indicators (cases, %)
| Indicators | The control group (n = 128) | The observation group (n = 45) | t/χ2 | P | ||
|---|---|---|---|---|---|---|
| Gastrointestinal decompression before feeding | Yes | 95 (74.22%) | 30 (66.67%) | 0.947 | 0.330 | |
| No | 33 (25.78%) | 15 (33.33%) | ||||
| Diuretic application before feeding | Yes | 71 (55.47%) | 21 (46.67%) | 1.036 | 0.309 | |
| No | 57 (44.53%) | 24 (53.33%) | ||||
| Parenteral nutrition | Yes | 38 (29.69%) | 15 (33.33%) | 0.208 | 0.648 | |
| No | 90 (70.31%) | 30 (66.67%) | ||||
| Nutrient solution type | Whole protein type | 60 (46.88%) | 31 (68.89%) | 6.472 | 0.011 | |
| Short peptide type | 68 (53.12%) | 14 (31.11%) | ||||
| Feeding route | Nasointestinal tube | 34 (26.56%) | 29 (64.44%) | 20.635 | < 0.001 | |
| Nasogastric tube | 94 (73.44%) | 16 (35.56%) | ||||
| Protein intake | < 1.2 g/kg | 91 (71.09%) | 14 (31.11%) | 22.311 | < 0.001 | |
| ≥ 1.2 g/kg | 37 (28.91%) | 31 (68.89%) | ||||
| Feeding speed | < 20 ml/h | 17 (13.28%) | 6 (13.33%) | 21.276 | < 0.001 | |
| 20–50 ml/h | 85 (66.41%) | 14 (31.11%) | ||||
| > 50 ml/h | 26 (20.31%) | 25(55.56%) | ||||
| Enteral nutrition temperature | 18–22℃ | 88 (68.75%) | 20 (44.44%) | 8.386 | 0.004 | |
| 36–38℃ | 40 (31.25%) | 25 (55.56%) | ||||
| Energy intake | Carbohydrate intake (kcal/d) | 1400 ± 400 | 1500 ± 300 | 1.531 | 0.128 | |
| Lipid intake (kcal/d) | 750 ± 160 | 800 ± 150 | 1.832 | 0.069 | ||
| Mineral intake | Potassium (mmol/d) | 3.45 ± 0.52 | 3.46 ± 0.49 | 0.113 | 0.911 | |
| Magnesium (mmol/d) | 0.69 ± 0.30 | 0.40 ± 0.33 | 1.686 | 0.094 | ||
| Phosphorus (mmol/d) | 0.56 ± 0.22 | 0.57 ± 0.25 | 0.253 | 0.801 | ||
Multivariate logistic regression analysis of concurrent RS
Taking the occurrence of RS as the dependent variable, the statistically significant variables in Tables 1 and 2 were included in the multivariate logistic regression analysis. The assignment of independent variables was shown in Table 3. The results showed that age ≥ 60 years (OR = 3.036, 95%CI: 1.784–5.462), high risk of NRS2002 score (OR = 4.001, 95%CI: 1.567–6.582), and mechanical ventilation time ≥ 3 days (OR = 3.251, 95%CI: 2.136–5.784), APACHE II score > 20 points (OR = 3.461, 95%CI: 1.365–6.254), feeding rate > 50 ml/h (OR = 3.784, 95%CI: 1.213–5.458), protein intake ≥ 1.2 g/Kg (OR = 5.496, 95%CI: 1.145–8.859), enteral nutrition temperature 36–38℃ (OR = 3.564, 95%CI: (1.023–5.645) was an independent risk factor for refeeding syndrome in patients with enteral nutrition in the ICU (P < 0.05, Table 4).
Table 3.
Assignment of independent variables
| Variable | Assignment | |
|---|---|---|
| X1 | Diabetes history | No = 0, yes = 1 |
| X2 | BMI | ≥ 18.5 kg/m2 = 0, < 18.5 kg/m2 = 1 |
| X3 | Age | < 60 = 0, ≥ 60 = 1 |
| X4 | Cerebrovascular disease | No = 0, yes = 1 |
| X5 | Severe pneumonia | No = 0, yes = 1 |
| X6 | Feeding route | Nasogastric tube = 0, Nasointestinal tube = 1 |
| X7 | Nutrient solution type | Short peptide type = 0, Whole protein type = 1 |
| X8 | NRS 2002 score | Low risk = 0, medium risk = 1, high risk = 2 |
| X9 | Duration of mechanical ventilation | < 3 d = 0, ≥3d = 1 |
| X10 | APACHE II score | < 10 = 0, 10 ~ 20 = 1, > 20 = 2 |
| X11 | Feeding speed | 20–50 ml/h = 0, > 50 ml/h = 1 |
| X12 | Protein intake | < 1.2 g/kg = 0, ≥1.2 g/kg = 1 |
| X13 | Enteral nutrition temperature | 18–22℃=0, 36–38℃=1 |
| Y | RS | No = 0, yes = 1 |
Table 4.
RS-related multivariate logistic regression analysis
| Indicators | β | SE | Wald | P | OR | 95%CI |
|---|---|---|---|---|---|---|
| X1 | 0.356 | 1.021 | 0.342 | 0.104 | 2.151 | 0.856–4.151 |
| X2 | 0.345 | 1.025 | 0.328 | 0.169 | 2.164 | 1.564–4.361 |
| X3 | 0.985 | 0.345 | 8.277 | 0.021 | 3.036 | 1.784–5.462 |
| X4 | 0.385 | 1.406 | 0.194 | 0.348 | 2.745 | 1.869–5.231 |
| X5 | 0.385 | 1.362 | 0.208 | 0.284 | 2.594 | 1.765–4.568 |
| X6 | 0.416 | 1.658 | 0.151 | 0.365 | 3.051 | 2.051–6.345 |
| X7 | 0.458 | 1.823 | 0.138 | 0.451 | 2.461 | 1.236–4.358 |
| X8 | 1.784 | 0.415 | 10.372 | < 0.001 | 4.001 | 1.567–6.582 |
| X9 | 0.896 | 0.451 | 4.182 | 0.029 | 3.251 | 2.136–5.784 |
| X10 | 0.849 | 0.316 | 8.490 | 0.016 | 3.461 | 1.365–6.254 |
| X11 | 1.008 | 0.475 | 4.460 | 0.029 | 3.784 | 1.213–5.458 |
| X12 | 1.184 | 0.318 | 11.723 | < 0.001 | 5.496 | 1.145–8.859 |
| Enteral nutrition temperature 36–38℃ | 0.815 | 0.316 | 7.149 | 0.024 | 3.564 | 1.023–5.645 |
Nutritional status of RS patients before and after targeted nursing strategies intervention
After the intervention of targeted nursing strategies, the serum levels of phosphorus, potassium, magnesium, albumin, and prealbumin were obviously elevated than before (P < 0.05, Table 5; Fig. 2).
Table 5.
Nutritional status of RS patients before and after targeted nursing strategies intervention (‾x ± s)
| Time | Phosphorus (mmol/L) | Phosphorus (mmol/L) | Phosphorus (mmol/L) | Albumin (g/L) | Pre-albumin (mg/L) |
|---|---|---|---|---|---|
| Before intervention (n = 45) | 0.55 ± 0.18 | 3.40 ± 0.21 | 0.64 ± 0.26 | 29.82 ± 4.25 | 130.70 ± 36.20 |
| After intervention (n = 45) | 0.97 ± 0.31 | 3.82 ± 0.42 | 0.80 ± 0.17 | 36.55 ± 5.89 | 156.40 ± 42.45 |
| t | 7.860 | 6.000 | 3.455 | 6.216 | 3.090 |
| P | < 0.001 | < 0.001 | 0.001 | < 0.001 | 0.003 |
Fig. 2.
Scatter plot of changes in nutritional markers of RS patients before and after targeted nursing intervention. A: Serum phosphorus (mmol/L) B: Serum potassium (mmol/L) C: Serum magnesium (mmol/L) D: Albumin (g/L) E: Prealbumin (mg/L). The blue circle represents before the intervention (n = 45), and the red triangle represents after the intervention (n = 45). Paired t-tests were used, with ***P < 0.001 and **P < 0.01, indicating that all indicators improved significantly after the intervention. Each data point represents one patient, and the point cloud distribution shows an overall upward trend
Discussion
RS is a common clinical nutritional treatment complication in ICU patients. Critically ill patients need to consume a large amount of vitamins and electrolytes under high stress and high metabolism. Enteral feeding can induce insulin secretion and redistribute intracellular and extracellular electrolytes. A large amount of potassium ions, magnesium ions, and phosphates enter cells, leading to electrolyte disorders mainly caused by hypophosphatemia. The pathological mechanism of RS is the transformation obstacle from catabolism to anabolism in the body. Hypophosphatemia is the most representative characteristic of RS. In addition, due to the acceleration of synthetic metabolism, a large amount of vitamins and electrolytes are further consumed. Therefore, ICU patients have a higher risk of developing RS after enteral refeeding [4, 14]. At the same time, in the state of starvation or malnutrition, the body is in a catabolic state, and muscle proteins are broken down to provide energy, resulting in the release of intracellular electrolytes such as phosphorus, potassium, and magnesium to the outside of the cell. After refeeding, anabolism suddenly accelerates, requiring large amounts of vitamins such as thiamine to participate in metabolic reactions. However, in the process of rapid nutritional supplementation, if vitamin supplementation is not timely, it will affect the energy metabolism and the activities of a variety of enzymes in cells, and further aggravate metabolic disorders [15]. Thiamine deficiency leads to decreased pyruvate dehydrogenase activity, which prevents the normal conversion of pyruvate to acetyl-coa into the tricarboxylic acid cycle, thereby affecting the energy production of cells and leading to cell dysfunction. It further aggravates electrolyte disturbance, affects the normal function of multiple systems such as the heart, nerve, and muscle, and causes multi-system clinical symptoms such as arrhythmia, respiratory failure, and disturbance of consciousness [16]. According to the existing literature reports, the incidence range of RS among patients undergoing enteral nutrition in the ICU is 10-30% [4, 5]. In this study, the incidence of RS was 26%, which was at the upper limit of this range and differed from the results of most studies. The main reasons were that 66.67% of the included subjects were elderly patients aged ≥ 60 years, 44.44% had an APACHEII score > 20 points, and 48.89% had a mechanical ventilation time ≥ 3 days. All of them are at high risk of RS, and most studies with a low incidence rate may have excluded such severe patients. In addition, this study adopted a three-level diagnostic criterion (mild to severe), covering the extent of electrolyte decline and organ dysfunction. However, some literature only defined severe electrolyte imbalance or organ failure as RS, resulting in a low reporting rate. As the medical community has shifted the focus of research on RS from lean malnutrition to critically ill patients in recent years, how to reduce the incidence of RS in ICU enteral nutrition patients has become a focus of research for healthcare professionals.
Multivariate logistic regression analysis in our study pointed out that age ≥ 60 years, NRS 2002 score > 5, duration of mechanical ventilation ≥ 3 days, APACHE II score > 20, feeding speed > 50 ml/h, protein intake ≥ 1.2 g/kg and enteral nutrition temperature 36–38℃ were independent risk factors of enteral nutrition patients complicated with RS in ICU. Early assessment of whether patients with enteral nutrition have these above risk factors is of great significance in reducing the occurrence of RS. With the aggravation of social aging, the proportion of elderly patients in ICU has increased. Most elderly people are accompanied by basic diseases such as cardiovascular and cerebrovascular diseases, and tumors, and are in a long-term state of malnutrition. Moreover, elderly people have low basal metabolism, low immune function, elevated APACHE II scores, and poor tolerance to malnutrition, making them a high-risk population for RS [17]– [18]. Malnourished patients are physically weak and often suffer from hypophosphatemia, which can lead to damage to diaphragm contraction function. Patients have difficulty breathing and in severe cases require mechanical ventilation, which is one of the important factors leading to RS. Therefore, patients with an increased NRS 2002 score have a higher risk of developing RS. According to relevant data [19, 20], critically ill patients with NRS 2002 scores > 3 are mostly elderly or those with severe illnesses. These patients have high nutritional needs, usually supplemented by increasing the calorie and protein content of the nutrient solution. However, consuming a large amount of nutrients can lead to increased synthesis metabolism and a sharp increase in insulin secretion, rapid consumption, and redistribution of electrolytes, leading to the occurrence of RS [21]. Some foreign studies suggest that feeding speed, protein intake, and enteral nutrition temperature during the process of enteral nutrition may also affect the occurrence of RS [22, 23], which is similar to the results of our present study. Research has shown that [24, 25] increasing the temperature of enteral nutrient solution to near body temperature can enhance gastrointestinal tolerance. However, increased temperature of the nutrient solution and accelerated feeding rate can further accelerate the absorption and synthesis of nutrients, and consume a large amount of substances such as thiamine and phosphate, thus increasing the risk of RS. The increase in protein and calorie intake requires the consumption of more electrolytes and vitamins to participate in synthetic metabolism. Therefore, the results of this study indicated that patients with protein intake ≥ 1.2 g/kg had a higher risk of RS. In addition, in the ICU setting, patients usually receive multiple interventions, which may become potential confounding variables and affect the study results. Some diuretics can promote the excretion of electrolytes such as potassium and magnesium, leading to further electrolyte imbalance and increasing the risk of refeeding syndrome. Some glucocorticoids may affect glucose metabolism, interfere with the normal regulation of blood glucose, increase the difficulty of blood glucose control, and then affect nutritional management in the process of refeeding [26]. In addition, the patient’s comorbidities can also have an impact on the outcome. Patients with diabetes mellitus have abnormal glucose metabolism and are more prone to blood glucose fluctuations during enteral nutrition, which increases the risk of refeeding syndrome. In patients with cardiac insufficiency, the heart’s pumping function is limited, and the risk of fluid retention is increased, which affects the delivery and metabolism of nutrients and also interferes with the judgment and treatment of refeeding syndrome [25].
RS can lead to electrolyte disorders such as low phosphorus, low magnesium, low potassium, and high sodium, as well as multi-system clinical symptoms such as arrhythmia and liver and kidney dysfunction. It not only affects the treatment efficiency of patients, but can also lead to death in severe cases [16, 27]. Therefore, targeted nursing interventions may reduce the incidence of RS. Our present study screened patients who needed key care based on risk factors and closely observed changes in their condition. We monitored and promptly corrected electrolyte disorders as early as possible, and developed targeted enteral nutrition plans based on individual patient conditions. We analyzed the fluid retention of patients and gave them targeted treatment, closely monitored the changes in blood glucose, and adjusted the enteral nutrition program according to blood glucose. The experiment found that compared to routine care, the levels of serum phosphorus, potassium, magnesium, albumin, and prealbumin in RS patients who received targeted nursing interventions were much higher than before the intervention. It is suggested that targeted nursing strategies based on the influencing factors of RS in ICU enteral nutrition patients can effectively correct the metabolic disorders related to RS, which is of great help in improving patients’ physical fitness, accelerating their recovery speed, and improving their prognosis.
In terms of clinical significance, this study was the first to systematically analyze the association between nutritional management factors such as feeding rate, protein intake, nutrient solution temperature, and RS in patients undergoing enteral nutrition in the ICU. This study found that when the feeding rate was > 50 ml/h, the risk of RS increased by 3.8 times (OR = 3.784), when the protein intake was ≥ 1.2 g/kg, the risk increased by 5.5 times (OR = 5.496), and the OR value of the warm feeding fluid at 36–38℃ reached 3.564. These results revealed the intervention targets that ICU medical staff could actively regulate. For example, the risk of RS might be significantly reduced by delaying the initial feeding rate and controlling the rhythm of protein increment.
This is a retrospective study, which may be subject to information bias. Moreover, the sample size was only 173 patients, which was relatively small and may not cover all the circumstances that may affect the occurrence of RS, leading to a certain limitation of the universality of the study results. In addition, this study lacked long-term follow-up data on patients after they were transferred out of the ICU. Only the changes in nutritional indicators during their stay in the ICU were observed, and outcome indicators such as quality of life and readmission rate after discharge were not tracked. Therefore, it is impossible to assess the impact of RS and its risk factors on the long-term prognosis of patients, nor to determine whether targeted nursing intervention has sustained benefits after the end of the ICU stay. To a certain extent, this limited the clinical significance and promotion value of the research findings. In terms of influencing factor analysis, although the relationship between multiple factors and RS was explored in this study, the type of comorbidities was not analyzed in detail. Different types of comorbidities, such as cardiovascular disease, pulmonary disease, and endocrine disease, may affect the patient’s nutrition metabolism and tolerance to enteral nutrition through different pathophysiological mechanisms, and then affect the risk of RS. Future studies can expand the sample size, conduct prospective studies, increase long-term follow-up, and in-depth analyze the influence of potential factors such as the types of comorbidities on RS, so as to construct a more complete risk prediction model and provide more reliable guidance for clinical practice. Another important limitation of this study lies in that all patients diagnosed with RS received targeted nursing intervention, and there was a lack of untreated patients with RS as a control. Although timely intervention for patients with RS is necessary from the perspectives of ethics and clinical practice, this design makes it impossible to directly compare the differences between “intervention” and “natural disease course”, and it is difficult to completely rule out the contributions of “treatment itself” and “natural recovery of the disease” to the improvement of indicators. In addition, this study did not evaluate clinical hard endpoints such as ICU length of stay, mortality rate, and incidence of organ failure. Moreover, there was a lack of long-term follow-up data for patients after they were transferred out of the ICU. Only the changes in nutritional indicators during their stay in the ICU were observed, and outcome indicators such as quality of life, readmission rate, and organ function recovery after discharge were not tracked. Therefore, it is impossible to assess the impact of RS and its risk factors on the long-term prognosis of patients, nor can it be determined whether a targeted nursing intervention has a sustained improvement effect after the end of the ICU stay.
In general, age, NRS 2002 score, and duration of mechanical ventilation are independent risk factors for RS in patients with enteral nutrition in the ICU. Nursing countermeasures such as electrolyte monitoring and individualized nutrition programs for risk factors can significantly improve the serum electrolytes and nutritional indicators of patients with RS. Due to ethical requirements, all patients diagnosed with RS received intervention measures. There was a lack of parallel control groups without intervention. Therefore, the contribution of natural recovery or standard ICU care to the improvement of indicators could not be completely ruled out. For example, the rebound of serum electrolytes may be related to the routine electrolyte replacement therapy in the ICU, rather than simply attributed to the targeted nursing strategy of this study. Meanwhile, high-risk patients without RS should be included as a prevention cohort to verify whether early intervention (such as delaying the feeding rate and limiting the protein load) can reduce the incidence of RS, thereby establishing a clinical pathway with both diagnostic and preventive value.
Acknowledgements
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Clinical trial number
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Authors’ contributions
Dongmei Yan confirmed the authenticity of all the raw data and edited the manuscript, Dongmei Yan and Jian Wang collected data and processed the data. Jian Wang conducted the statistics. Jian Wang reviewed and revised the article. All authors read and approved the final manuscript.
Funding
Not applicable.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
This study was approved by The Ethics Committee of Guang’an People’s Hospital. Written informed consent to participate was obtained from all of the participants in the study.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Consent for publication
Not Applicable.
Competing interests
The authors declare no competing interests.
Footnotes
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.