The Clinical Impact of Malnutrition

Details of the clinical impact of malnutrition in different patient populations are provided.

Malnutrition describes a deficiency or imbalance of energy, protein and other nutrients that causes adverse effects on tissue, body shape, size and composition and function and clinical outcome. The effects of malnutrition on morbidity result chiefly from impaired immune function, delayed wound healing and convalescence from illness and decreased functional status.1

Clinical impact of malnutrition in pediatric patients
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Protein-calorie malnutrition in children negatively affects the function of numerous body systems. Poor nutrition during critical periods of growth can cause growth slowing and stunting.2 Table 1 summarizes how the immune system, endocrine, cardiovascular, respiratory and gastrointestinal systems are affected, as well as the neurological effects.3

Table 1: The clinical impact of pediatric malnutrition3

Physiologic system Clinical impact
Immune system Reduced immunity due to atrophy of the thymus, lymph nodes and tonsils
Reduced T-lymphocytes
Reduced immunoglobulin A
Increased susceptibility to infection
Endocrine system Reduced thyroid hormones
Increased growth hormone
Glucose intolerance
Gastrointestinal system Malabsorption due to atrophy of villi
Bacterial overgrowth
Atrophy of the pancreas
Cardiovascular system Reduced cardiac output proportionate to weight loss
Bradycardia, arrhythmias, hypotension
Respiratory system Impaired breathing response to hypoxia
Neurological effects Reductions in number of neurons and synapses
Slowed brain growth
Delays in global brain function, motor function and memory

Malnutrition in neonates and preterm infants
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Although there is some scope for 'catch-up' growth when feeding improves, malnutrition during infancy has a long-term effect on development.2 High protein intake during the first week of life has been shown to be associated with a reduced likelihood of growth restriction (length <10th percentile) at 18 months of age in extremely low birth weight infants (odds ratio [OR]: 0.260 [CI: 0.076–0.907]; P=0.0345).4 A study of 109 preterm infants by Tan, Abernethy and Cooke showed strong correlations between weight, and mental and motor outcomes in the first year (3 months correlation coefficient for mental development index = 0.3, P=0.006 and for psychomotor developmental index = 0.37, P=0.001).5

Clinical impact of malnutrition in hospitalized adult patients
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Malnutrition has been shown to have several prognostic implications, including increased morbidity, mortality and costs of treatment in acute and chronic disease.1

The nutritional status of 1,886 patients in 13 European hospitals was assessed prospectively by Subjective Global Assessment (SGA) and anthropometric measurements. The analysis included risk factors for malnutrition and the impact of nutritional status on the length of hospital stay.6 Moderate and severe malnutrition were significantly associated with increased length of hospital stay when compared with well-nourished patients (Figure 1, average difference 4.6 days or 42%, P<0.001).6

Figure 1. Association of nutritional status with length of hospital stay6

Each patient was classified as either well nourished (SGA A), moderately or suspected of being malnourished (SGA B) or severely malnourished (SGA C).

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A prospective, observational study in Switzerland examined the relationship between clinical outcomes and energy balance in 48 consecutive surgical ICU patients.7 Total energy balance correlated with the number of total and infectious complications: the lower the energy received, the larger the negative energy balance and the higher the number of total and infectious complications (P=0.0001 with F=25.18 and P=0.049 with F=8.81, respectively after 7 days).7 A higher energy deficit also correlated significantly with longer ICU stay. Both energy balance at the end of the first week of the ICU stay and cumulative energy balance were the strongest predictors of prolonged ICU stay.

A prospective, observational study of 155 patients hospitalized for internal or gastrointestinal diseases at a university hospital in the Netherlands, also showed that the severity of malnutrition is potentially related to the risk of complications.8 On admission, 45–62% of patients were malnourished, as assessed by the SGA, Nutritional Risk Index (NRI) and Maastricht Index (MI). On multivariate analysis, adjusting for disease category and severity, ORs for the incidence of any complication in malnourished compared with well-nourished patients during hospitalization were 1.7 (95% CI: 0.8–3.6) for the SGA, 1.6 (95% CI: 0.7–3.3) for the NRI and 2.4 (95% CI: 1.1–5.4) for the MI. However, as the confounding factors adjusted for may be influenced by malnutrition itself, the actual risks of complications are likely to be higher than the adjusted ORs.8

Similar results were shown by Dvir et al. (2006) who performed a prospective, observational study of 50 ICU patients in Israel.9 They found a strong correlation between the negative energy balance versus the amount of total complications for critically ill patients: the more negative the energy balance, the higher the number of complications (P<0.01, r=0.75, Figure 2). The complications which correlated included adult respiratory distress syndrome, renal failure, need for surgery, pressure sores and total complication rate.9

Figure 2: Correlation between negative energy balance and total number of complications in 50 critically ill patients9

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Malnutrition is associated with an unfavorable clinical course. The impact of malnutrition on morbidity, mortality and length of hospital stay was evaluated in a prospective, analytical, cohort study of 161 consecutive trauma patients using the SGA to determine the prevalence of malnutrition.10 Multivariate analysis identified risk of malnutrition and ICU admission as risk factors for mortality (P=0.04, relative risk [RR]=4, 95% CI 1–15 and P=0.0001, RR=53, 95% CI 12–234). Malnutrition was also identified as a risk factor for the development of complications (P=0.003, RR=2.9, 95% CI 1.4–5.8) and length of hospital stay >14 days (P=0.01, RR=2.3, 95%CI 1.2–4.7).10

In the EuroOOPS study,11 patients admitted to 26 participating hospitals were evaluated for signs of malnutrition utilizing the NRS-2002 (Nutrition Risk Screening) tool. This tool is based on observed outcomes in controlled trials and identifies patients likely to benefit from nutritional support by an improved clinical outcome. In total, 5,051 patients were included in the analysis from the specialties of surgery, general internal medicine, gastroenterology, oncology, intensive care and geriatrics. The NRS-2002 screening was performed within 36 hours of admission. Of the 5,051 study patients, 33% were defined by NRS-2002 as 'at-risk'. Complications including death and increased length of stay were significantly more frequent in at-risk patients (OR=3.47, P<0.001). Following admission, at-risk patients were discharged home or transferred within the hospital to another department and further follow up was not obtained. Due to the selection of participating departments, the authors concluded that this data cannot be extrapolated to reflect the general incidence of hospital malnutrition.

Clinical impact of malnutrition in patients with congestive heart failure
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Independent of established markers of congestive heart failure (CHF) prognosis, the presence of cardiac cachexia predicts a worse prognosis.12–14 In a prospective study of 205 patients (without cancer and aged approximately 75 years), consecutively admitted on an emergency basis to a hospital in Sweden, mortality was significantly higher in malnourished patients than in non-malnourished patients (44% versus 18%, respectively; P<0.001) over the 9-month follow-up period.15 Malnourished patients were identified as having at least three nutritional variables (which included weight index, triceps skinfold thickness, arm muscle circumference, serum albumin and delayed cutaneous hypersensitivity reaction) below the reference range. In malnourished patients with CHF, the mortality rate was even higher (80%) than those without CHF.15

In a recent prospective, observational, single-center study conducted in the UK (N=538), it was shown that the NRI is a prognostic marker for outpatients with CHF. Based on the NRI, risk of malnutrition was present in 23% of patients. Univariable predictors of mortality included age (Chi-square: 59, P<0.001), urea (Chi-square: 40, P<0.001) and NRI (Chi-square: 25, P<0.001). The NRI was also found to be an independent predictor of outcome on multivariable analysis (Chi-square: 12, P<0.001).16

Adequate nutrition is essential for proper wound healing and pressure ulcers
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Wound healing represents a state of metabolic stress, and the more severe the injury, the greater the metabolic stress.17 The stressed state causes increased metabolic activity and protein requirements.17–19 Protein depletion is associated with prolonged wound inflammation and inhibition of wound remodeling.20 Involuntary weight loss and protein calorie malnutrition (PCM) are also risk factors for impaired wound healing.21

A multicenter, cross-sectional audit of nutritional status of patients in hospitals and residential care facilities utilizing the SGA found that malnutrition at least doubled the likelihood of a patient having a pressure ulcer (OR=2.6 in acute care facilities and 2.0 in residential care facilities). Increasing severity of malnutrition was associated with an increased risk of pressure ulcer occurrence and severity.22

In a cross-sectional, multicenter study of nursing home (N=2,393) and hospital (N=4,067) patients assessing the relationship between malnutrition and pressure ulcers, there was an increase in the likelihood of malnourished patients (undesired weight loss of 5–10%) experiencing pressure ulcers in the hospital setting (regression coefficient 1.205, standard error=0.489, P=0.014, OR=3.336, 95% CI 1.279–8.697).23

Malnutrition in patients with cancer
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In a retrospective study of 1,555 patients treated for locally advanced or metastatic gastrointestinal tumors (esophageal, stomach, pancreas, colon or rectum), Andreyev et al demonstrated that patients experiencing weight loss at the time of presentation often have more severe dose-limiting toxicity leading to an average of 1 month less treatment than those without weight loss (120.25 days versus 150.5 days, P<0.0001).24 Based on a stratified analysis of all sites combined, weight loss was also associated with shorter failure-free survival (median, 5.1 months versus 6.3 months; hazard ratio [HR]=1.25, 95% CI 1.12–1.39), reduced performance status and quality of life (all P<0.0001) compared with those who had not lost weight.24 Patients in whom weight loss stabilized or was reversed had a longer period of failure-free survival (median: 13.7 months versus 8.5 months; P=0.0003) and overall survival (median: 15.7 months versus 8.1 months; P=0.0004) compared with those who continued to lose weight.24

In a prospective study of clinical outcomes and survival in patients with small cell lung cancer (SCLC), non-small-cell lung cancer (NSCLC) and mesothelioma, patients with weight loss and NSCLC or mesothelioma had a smaller decrease in symptoms with chemotherapy compared with those without weight loss.25 In addition, weight loss was an independent predictor of shorter overall survival in SCLC (RR=1.5, P=0.003), NSCLC (RR=1.33, P=0.009) and mesothelioma (RR=1.92, P=0.03) patients.25

Weight loss is also a concern in other types of malignancy such as breast cancer. For example, sarcopenia is associated with an increased risk of overall mortality in breast cancer survivors. In 471 breast cancer patients, appendicular lean mass was measured using dual X-ray absorptiometry scans. After a median follow-up of 9.2 years, 75 women were classified as sarcopenic. The authors found that sarcopenia was independently associated with overall mortality, regardless of adiposity measures (HR=2.86; 95% CI, 1.67–4.89, P<0.001).26

In general, malnourished cancer patients have a poorer response to chemotherapy, with both the rate of response and the duration of treatment being affected.27 Nutrition status also has a significant effect on sense of well-being and quality of life in cancer patients.28

An overview of the clinical impact of malnutrition in patients with cancer in illustrated in Figure 3.

Figure 3: Cancer causes a decline in nutritional status that leads to unfavorable clinical outcomes and reduced quality of life.29

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Cost burden of malnutrition
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A number of studies have shown that malnutrition is a substantial financial burden to healthcare systems. Factors contributing to this high cost burden have been reported to be more frequent hospital admissions, longer hospital stays and a higher risk of complications.11,30–32

In 1988, Reilly et al. performed a retrospective review of 771 patient records in two hospitals to determine the likelihood of malnutrition on costs and charges in the US. It was determined that the likelihood of malnutrition increased excess direct variable costs and charges by $1,738 and $3,557 per patient, respectively (normalized to 1985 $US). The occurrence of complications increased these figures to $2,996 and $6,157, respectively.33

A retrospective, cohort study reviewing 709 adult patients in Brazilian hospitals showed that malnourished patients represented a mean daily expense of US $228/patient compared to the well nourished mean daily expense of US $138/patient. In this study, very few patients received nutrition support despite the high prevalence of malnutrition at admission.30

Freijer at al performed a cost-of-illness analysis to calculate the additional costs of disease related malnutrition in adults. It evaluated patients in the hospital, nursing- and residential home and home care settings. They estimated the total additional costs of managing adult patients with disease related malnutrition to be € 1.9 billion in 2011 in the Netherlands.34

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