16. Nutritional Interventions Following Stroke pg. 1 of 37 www.ebrsr.com EBRSR [Evidence-Based Review of Stroke Rehabilitation] 16 Nutritional Interventions Following Stroke Norine Foley MSc, Robert Teasell MD, Marina Richardson MSc, Sanjit Bhogal MSc, Mark Speechley PhD (We gratefully acknowledge the contribution of Dr. Hillel Finestone) Last Updated: August 2013 Abstract Nutritional status following stroke can have a negative impact on functional recovery and mortality. Complications associated with malnutrition include a greater incidence of infections and pressure sores, and longer lengths of hospital stays. Clinical nutritional management requires effective methods of assessment, an understanding of the underlying causes of nutritional deficiencies, and effective methods of administering nutrients via feeding techniques and supplementation. In this review, the incidence of malnutrition post stroke is evaluated and markers used to identify deficiencies are discussed. A summarization of potential causes of nutritional deficiencies is provided including hypermetabolism, increased catabolism, and gastrointestinal and food intake issues. Interventions including enteral feeding and oral supplementation are then discussed as well as treatments for dysphagia.
Transcript
16. Nutritional Interventions Following Stroke pg. 1 of 37 www.ebrsr.com
EBRSR [Evidence-Based Review of Stroke Rehabilitation]
16 Nutritional Interventions Following
Stroke
Norine Foley MSc, Robert Teasell MD, Marina Richardson MSc, Sanjit Bhogal MSc, Mark Speechley PhD
(We gratefully acknowledge the contribution of Dr. Hillel Finestone)
Last Updated: August 2013
Abstract
Nutritional status following stroke can have a negative impact on functional recovery and mortality. Complications associated with malnutrition include a greater incidence of infections and pressure sores, and longer lengths of hospital stays. Clinical nutritional management requires effective methods of assessment, an understanding of the underlying causes of nutritional deficiencies, and effective methods of administering nutrients via feeding techniques and supplementation. In this review, the incidence of malnutrition post stroke is evaluated and markers used to identify deficiencies are discussed. A summarization of potential causes of nutritional deficiencies is provided including hypermetabolism, increased catabolism, and gastrointestinal and food intake issues. Interventions including enteral feeding and oral supplementation are then discussed as well as treatments for dysphagia.
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Key Points
Prevalence of Malnutrition
Malnutrition is a relatively common problem post stroke.
Patients consume fewer calories and protein following stroke.
Patients are not hypermetabolic acutely following stroke. Nutritional Interventions
Intragastric feeding tubes are associated with fewer complications, compared with naso-enteric tubes, when patients require nutrition support for at least 28 days.
Oral supplementation improves energy and protein intake although it does not improve functional outcomes.
The one-year survival rate of patients with feeding tubes, discharged to the community varied widely following stroke.
The use of TPN has not been studied in the stroke population.
Dr. Robert Teasell 801 Commissioners Road East, London, Ontario, Canada, N6C 5J1
Table of Contents ........................................................................................................ 3
16. Nutritional Interventions Following Stroke ............................................................. 4
16.1 Markers Used in the Assessment of Nutritional Status ................................................ 4 16.2 The Prevalence of Malnutrition Post Stroke ................................................................ 5
16.3 Factors Associated With the Development of Malnutrition ....................................... 11
16.3.1 Hypermetabolism Following Stroke ........................................................................... 12
16.3.2 Increased Catabolism Following Stroke ..................................................................... 13
16.3.3 Gastrointestinal Function Following Stroke ............................................................... 14
16.3.4 Nutrient Intake Following Stroke ............................................................................... 15
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16. Nutritional Interventions Following Stroke
Declines in nutritional status following stroke are potentially important because of the negative impact on functional recovery and mortality. Preliminary results from the FOOD trial reported poor nutritional status was associated with an increase in the odds of death and dependency at six months after adjusting for a number of confounders (OR 1.82; 95% CI, 1.34 to 2.47) (FOOD Trial Collaboration 2003). Poor nutrition has been found to predict lower functional status following stroke. In a study focusing on the functional consequences of malnutrition in stroke rehabilitation, patients’ serum albumin used as an marker of nutritional status was associated with poorer functional mobility, increased complications, and lower self-care scores (Aptaker et al. 1994). Davalos et al. (1996) also reported that malnutrition after the first week of stroke was associated with an increased risk of poor outcome (death or dependency) at one month, a greater incidence of infections and pressure sores, and longer lengths of hospital stays, among a group of 104 patients with acute stroke. Patients, who were considered malnourished had an elevated risk of death or poor outcome at 30 days follow-up (OR, 3.5; 95% CI, 1.2 to 10.2). Gariballa et al. (1998a) investigated the associations between a variety of anthropometric and biochemical parameters assessed on admission to hospital and outcome following stroke, among 201 patients. After adjusting for age, comorbid conditions, sex, medications and stroke severity, serum albumin was related to an increase in death at three months. Each decline of 1 g/L in serum albumin, measured on admission, was associated with a 1.13-fold increase in death at follow-up.
16.1 Markers Used in the Assessment of Nutritional Status
Currently, there is no universally accepted gold standard for the assessment of nutritional status. The identification of malnutrition is typically based on the evaluation of a combination of biochemical and anthropometric markers and is inferred, based on either a single value or multiple values, falling outside of specific population reference ranges or below a certain percentile within these ranges. Since the combination of markers used and the cut-off values are chosen arbitrarily, reports of malnutrition will vary widely. As a result, the true incidence of malnutrition following stroke is likely unknown. Both biochemical and anthropometric indicators are used in the evaluation of nutritional assessment Table 16.1 presents some the more commonly used biochemical indicators used as well as their limitations.
Unfortunately, many of these nutrition sensitive markers are affected independently by factors associated with stroke (or any other acute illness), complicating the process of evaluating the response to nutritional interventions. Although both albumin and prealbumin are used extensively in nutritional assessment, the hepatic production of these two proteins is known to be down-regulated during periods of acute illness, independent of nutritional status (Fleck 1989; Gabay & Kushner 1999). While hypoalbuminemia has been repeatedly shown to be associated with morbidity and mortality the causal mechanism is not clear. Akner and Cederholm (2001) did not demonstrate a relationship between protein and caloric intakes and serum albumin in their institutionalized elderly population. Difficulties arise due to the fact that biochemical markers of nutrition can change rapidly, whereas a change in nutritional status is considered more latent and takes longer to manifest. In addition, the presence of concurrent infection or elevations in temperature can affect serum markers, mimicking signs of malnutrition.
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Measures of nutrition assessment also include indicators of skeletal muscle mass and subcutaneous fat stores measures. Examples of these measurements include weight, mid arm muscle circumference and skinfold thickness. While declines of these indicators may be associated with the development of malnutrition, factors secondary to stroke may also affect the sensitivity of these measures. Skeletal muscle losses may occur over prolonged periods of time as a result of atrophy, secondary to immobility (Deitrick et al. 1948; Schonheyder et al. 1954). It may be difficult to differentiate between these losses and those that are associated with inadequate food intake, adding to the difficulties of evaluating nutritional status. Malnutrition is usually considered to be a state that develops over time in response to inadequate intake, relative to need and results in gradual weight loss with associated losses of lean body mass (muscle) and subcutaneous fat stores. Since the identification of malnutrition among the majority of studies was made on the basis of both anthropometric and biochemical markers it is possible that the higher percentage of patients reported to be malnourished in studies that measured malnutrition at a later point in the hospitalization period reflected non-nutritional changes in body composition.
16.2 The Prevalence of Malnutrition Post Stroke
The prevalence of malnutrition following stroke has been reported to be between 6% and 62 % (see Table 16.2). If the criteria are widened to include the secondary criteria used in two studies, the range of estimates broadened to 1.3% to 73%. Some of this variability can likely be attributed to differences in patient characteristics and the timing of assessments among studies. However, a substantial proportion of the variation in estimates may also be explained by the heterogeneity of nutritional assessment. Among the 22 trials reviewed below, 18 different assessment methods were used. Only five trials used previously validated assessment methods; Subjective Global Assessment (SGA), “an informal assessment”, and Mini Nutritional Assessment (MNA). The nutritional assessment methods used in the remaining studies used had not been validated previously. The three valid assessment tools mentioned above were created for differing purposes. The informal “eyeball” assessment was developed specifically to classify patients into groups based on nutritional state within the context of the large, multi-centred FOOD trials. Subjective Global Assessment was designed for use in the prediction of risk for complications following general surgery following general surgery, based on pre-operative nutritional state, while Mini Nutritional Assessment, the third valid tool, was developed as a screening and assessment tool to identify geriatric patients at risk for malnutrition.
Table 16.1 Biochemical Markers of Nutritional Status (Manual of Clinical Dietetics, 2000)
Measure Limitations
Serum albumin Large body pool Poor specificity to nutritional changes
Not specific to nutritional status ↓ with acute illness
Serum transferrin Not specific to nutritional status ↓ with acute illness
Thyroxin Binding Prealbumin Not specific to nutritional status ↓ with acute illness
Retinol Binding Protein Not specific to nutritional status
Total Lymphocyte Count Poor sensitivity and specificity
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Although both SGA and MNA have been validated subsequently for use in other disease or injury states, validation of these tools for the assessment of individuals with stroke is lacking. In one study, a group of 35 patients with stroke, aged 60 to 89 years were assessed for nutritional status using laboratory measures and the SGA and MNA. There was strong correlation between SGA and objective measures when patient nutrition status was classified as normal, mildly malnourished, moderately malnourished and severely malnourished (r=0. 449), and strong correlation between MNA and objective measures when patient nutrition status was dichotomized (well-nourished vs. at risk of malnutrition or malnourished) (r=0.520) (Kim et al. 2013).
Author/Year/Country/Study
Type
% of patients identified with malnutrition and the timing of assessment
Criteria used to detect malnutrition
Axelsson et al. (1988) Sweden Prospective case series
16% within 4 days of symptom onset (n=100) 22% at hospital discharge (n=78)
≥ 2/6 nutrition variables below the reference limit: serum albumin (<38 g/L male, <37 g/L female), prealbumin (<.18 g/L), transferrin (<1.7 g/L male, <1.5 g/L female), body weight (<80% relative body weight), tricep skinfold thickness (4 levels based on age), arm muscle circumference (4 levels based on age).
DePippo et al. (1994) USA 5 (RCT)
6.1% at any point between rehabilitation hospital admission (median of 4.6 weeks post stroke) and discharge (n=115)
Albumin < 2.5 g/dL or sustained ketonuria without glycosuria > 2 weeks
Unossen et al. (1994) Sweden Prospective case series
8% within 2 days of symptom onset (n=50)
≥ 3 nutrition variables below cut-off levels, including 1 of each of the anthropometric, serum protein and skin test measurements: weight (< 80% of reference value), tricep skinfold (<6 mm male, <12 mm female), arm muscle circumference (4 levels based on age and sex), delayed hypersensitivity skin testing (< 10 mm induration), serum albumin (<36 g/L), prealbumin (<.20 g/L male, <.18 g/L female).
Finestone et al. (1995) Canada Prospective case series
49% on admission to rehabilitation unit (mean of 22 days post stroke) (n=49) 34% at 1 month (n=32) 22% at 2 months (n=9) 19% at follow up (2-4 months) (n=42)
≥ 2/6 nutrition variables below the reference limit: serum albumin (<35 g/L) , transferrin (<2.0 g/L), total lymphocyte count (<1800n/ mm3) body weight (<90% of reference weight, or <95% of usual weight, or body mass index < 20), sum of 4 skinfolds (< 5th percentile of reference population), midarm muscle circumference (< 5th percentile of reference population).
Davalos et al. (1996) Spain Prospective case series
16.3% within 24 hrs of hospital admission (n=104) 26.4% after 1 week (n=91) 35% after 2 weeks (n=43)
Serum albumin < 35 g/L or tricep skinfold or midarm muscle circumference < 10th percentile of reference population.
Choi-Kwon et al. (1998) South Korea Cross-Sectional
25% patients with ischemic stroke 62% patients with hemorrhagic stroke Assessed in the acute period of stroke 13% control subjects
≥ 1 biochemical marker and ≥ 2 anthropometric markers below the lower limits of the reference limits. (Lean body mass, abdominal skinfold thickness, subscapular skinfold, triceps skinfold, all < 80% of reference values, body mass index < 20), total lymphocyte count < 1500/ mm3, hemoglobin < 12 g/dL, serum albumin <3.5 g/dL.
Aquilani et al. (1999)
30% at admission to rehabilitation (30±10 days post stroke) (n=150)
Loss of weight ≥ 10% but with actual weight lower than reference weight or loss of weight ≥ 5% plus one other
Table 16.2 The Prevalence of Malnutrition Following Stroke
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Italy Prospective cohort
abnormal marker: arm muscle area < 5th percentile, serum albumin < 35 g/L, Total lymphocyte count <1800n/ mm3.
Westergren et al. (2001b) Sweden Prospective case series
8% within 24 hrs of symptom onset (n=24) 29% at 1 month (n=24) 33% at 3 months (n=24)
1 abnormal weight measurement and at least 1 other abnormal marker: Body mass index < 20 or body weight, ≤ 80% of reference weight or weight loss > 5% since admission; Subnormal triceps skinfold or mid-upper arm muscle circumference or serum albumin < 36 g/L.
Westergren et al. (2001a) Sweden Prospective case series
32% within 6 days following hospital admission (n=162)
Author’s modified version of Subjective Global Assessment: A= Well nourished B= Well-nourished but at risk of becoming malnourished C= Suspected of being malnourished D= Severely malnourished SGA classes B or C or D =malnourished
Davis et al. (2004) Australia Prospective case series
16% within 24 hrs of symptom onset (n=185)
Subjective Global Assessment: A=Well nourished B=Moderately (or suspected of being malnourished C=Severely malnourished B or C =malnourished
Dennis et al. (2005a) UK 7 (RCT)
7.8% within 7 days of symptom onset (n=4,023)
Clinical judgement used to determine if a patient was undernourished, normal or overweight. (A more comprehensive assessment was carried out in 37% of patients)
Martineau et al. (2005) Australia Retrospective audit
19.2% within 2 days of symptom onset (n=73)
Patient Generated Subjective Global Assessment Scoring identical to SGA.
Hama et al. (2005) Japan Prospective cohort
22% within the first day of admission to a rehabilitation hospital- an average of 44 days post stroke based on serum albumin (n=51) 57% based on body mass index (BMI)
Either serum albumin < 40 g/L or BMI < 19.
Crary et al. (2006) USA Prospective case series
26.3% at hospital admission(n=76) Mini Nutritional Assessment score < 23.5.
Brynningsen 35% at one week post stroke(n=100) ≥2 abnormal values: serum albumin <550 mikromol/L,
Poels et al. (2006) The Netherlands Prospective cohort
Primary criteria: 35% at admission to rehabilitation (34 days post stroke) (n=69) 3% at 4 weeks following admission (n=60) Secondary criteria: 73% at admission to rehabilitation 54% at 4 weeks
Primary: Unintentional weight loss of more than 5% in one month or 10% in 6 months or Body Mass Index < 18 for subjects < 65 years or <22 for subjects ≥65years. Secondary: the presence of at least one subnormal primary or secondary outcome criteria: Serum albumin < 35 g/L, fat free mass ≤ 16 kg/m2 (men) or 15 kg/m2 (women), tricep skinfold < 90% of 12.5 mm (men) or 16.5 mm (women), mid arm muscle circumference < 90% of 25.3 cm (men) or 23.3 cm (women).
Yoo et al. (2008) South Korea Prospective cohort
12.2% within 24 hrs of symptom onset (n=131) 19.8% at one week
Any single indicator below reference limits: Weight loss of ≥10% for the past 3 months or ≥ 6% during first week of admission, weight index (actual weight in relation to reference weight) <80%, serum albumin < 30 g/L, serum transferrin < 1.5 g/L, serum prealbumin < 0.10 g/L.
Chai et al. (2008) USA Cross-sectional
8.2% of infirmary residents with a history of stroke (n=61)
Serum albumin < 35 g/L or BMI < 18.5
Lim & Choue (2010) Korea Prospective cohort
19 (26%) well-nourished 36 (49.3%)moderately malnourished 18 (24.7%) severely malnourished Timing not stated, but assessments took place following admission to hospital an average of 60 days post stroke.
Patient-generated Subjective Global Assessment
Crary et al. (2013) USA Prospective cohort
32% of ischemic stroke patients were identified as malnourished at admission, 33% at day 7 following hospitalization
Serum prealbumin level of < 15 mg/dL
Mosselman et al. (2013) Netherlands Prospective cohort
73 patients assessed at admission to hospital (between 2 and 5 days): 59 (81%) well nourished 10 (14%) at risk of malnutrition 4 (5%) malnourished 23 patients assessed at 9-12 days after admission to hospital: 8 (35%) well nourished 9 (39%) at risk of malnutrition 6 (26%) malnourished
Mini Nutritional Assessment score <17 (malnourished), 17-23.5 (at risk of malnutrition), ≥24 (well nourished)
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Dysphagia Eleven studies recruited patients both with and without dysphagia. Greater proportions of patients with dysphagia were classified as malnourished compared with patients with normal swallowing function in four trials: (19/59 vs.10/14, p=0.007) (Martineau et al. 2005); (16/24 vs. 15/67, p<0.001) (Davalos et al. 1996); (15/23 vs. 9/26, p=0.032) (Finestone et al. 1995); (4/5 vs. 17/56, p=0.044) (Chai et al. 2008). Poels et al. (2006) also reported a greater proportion of subjects with dysphagia was malnourished, although the result was not statistically significant (4/20 vs. 4/40, p= 0.233). Crary et al. (2006) did not demonstrate a significant association between the dysphagia and malnutrition assessed within several days of stroke (OR: 1.0; 95% confidence interval 0.4 to 2.8). In a subsequent study, this finding was repeated. In addition, a relationship between dysphagia and dehydration was reported. In a systematic review including the results from 8 studies, Foley et al. (2009) reported that the odds of being malnourished were increased given the presence of dysphagia following stroke. However, they also suggested that the relationship was not causal. While stroke size and location are the greatest determinants of swallowing function, it is also true that the presence of dysphagia is itself an indicator of greater stroke severity.
Stroke Type and Severity The relationship between stroke severity and malnutrition was examined in three studies (Davis et al. 2004; Dennis et al. 2005a; Yoo et al. 2008). Increasing stroke severity was associated with baseline malnutrition in one of these trials (Yoo et al. 2008). In all of these studies severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and was examined during the first several days following acute stroke. Only one study examined the relationship between stroke type and malnutrition (Choi-Kwon et al. 1998). The prevalence of malnutrition reported in this study was much higher among patients suffering from intracerebral hemorrhagic versus ischemic stroke; however, the authors suggested that the result was likely attributable to differences in pre-existing malnutrition between groups.
Variability of Assessment Criteria With the single exception of the two related FOOD trials, no two studies used the same criteria. Serum albumin and measures of weight were common to almost all of the studies. However, the cut-off points used to distinguish well-nourished from malnourished patients were chosen arbitrarily, as were the choice of reference populations and will potentially affect the degree and proportion of patients who are considered to be malnourished. For instance, most studies used a cut-off point for serum albumin level as 35 g/dL, (or using the American system 3.5 g/L) however, Hama et al. used a 40 g/L cut-off point while DePippo et al. used a much lower point of 2.5 g/L (DePippo et al. 1994; Hama et al. 2005). Foley et al. (2009b) conducted a systematic review of studies that had reported the prevalence of malnutrition following stroke. Eighteen studies meeting inclusion criteria were identified. The reported frequency of malnutrition ranged from 6.1% to 62%. Seventeen different methods of nutritional assessment were used. Four trials used previously validated assessment methods; Subjective Global Assessment (SGA), “an informal assessment”, and Mini Nutritional Assessment (MNA). The nutritional assessment methods used in the remaining studies used had not been validated previously. The authors suggested that the use of a wide assortment of nutritional assessment tools, most of them, previously not validated contributed to the wide range of estimates of malnutrition. The frequency with which both anthropometric and biochemical indicators were used in studies reporting on malnutrition are presented in Table 16.3.
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Biochemical Markers
Study Albumin Transferrin *TLC Prealbumin Ketonuria
Axelsson 1988 X X X
DePippo 1994 X X
Unosson 1994 X X X
Finestone 1995 X X X
Davaolos 1996 X
Choi-Kwon 1998 X X
Aquilani 1999 X X
Hama 2005 X
Poels 2006 X
Brynningsen 2007 X X
Yoo 2008 X X X
Chai et al. 2008 X
Crary et al. 2012 X
Anthropometric Markers
Study Weight Fat (TSF, SS) Muscle (AMC, MAMC)
Axelsson 1988 X X X
DePippo 1994
Unosson 1994 X X X
Finestone 1995 X X X
Davaolos 1996 X X
Choi-Kwon 1998 X X X
Aquilani 1999 X X
Hama et al. 2005 X
Poels 2006 X X X
Brynningsen 2007 X X
Yoo 2008 X
Chai et al. 2008 X
Composite Clinical Assessments
Westergren et al. 2001a), FOOD I & II (2005), Martineau et al. 2005, Crary et al. 2006, Lim et al. 2010, Mosselman et al. 2013
* total lymphocyte count
There was variability in the percentiles chosen for anthropometric cut-off points, if they were even identified. Choi-Kwon et al. (1998) used an undefined reference population, while Unosson et al. appeared to choose specific, age-dependent cut-off points that were unreferenced and did not appear to be based on population norms per se (Unosson et al. 1994). Finestone et al., Davalos et al., and Axelsson et al. all used population-based national survey results as their reference standards (Axelsson et al. 1988; Davalos et al. 1996; Finestone et al. 1995). However, there was no consistency in choosing cut-off values; some studies used the 5th percentile (Finestone et al. 1995), while another used the 10th (Elmstahl et al. 1999). Axelsson et al. and Choi-Kwon et al. (1998) simply made reference to “low values” when they defined their cut-off threshold (Axelsson et al. 1988). Implicit in the assessment of malnutrition is that thin people, relative to the rest of the reference population, are malnourished.
Table 16.3. Individual Nutrition Markers Used in the Reviewed Studies
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Timing of Assessment The timing of the assessment could have also explained the variability of the prevalence rates of reported malnutrition. Among the 13 studies that assessed nutritional status within one-week of stroke the frequency of malnutrition was < 20% in 9 of the studies (Axelsson et al. 1988; Davalos et al. 1996; Davis et al. 2004; Dennis et al. 2006; Dennis et al. 2005a, 2005b; Martineau et al. 2005; Unosson et al. 1994; Westergren et al. 2001b; Yoo et al. 2008). Frequency of malnutrition was 26% at 10 days after admission to hospital in one study (Mosselman et al. 2013). Among the 7 trials that assessed nutritional state between 22 and 44 days following stroke, at admission to rehabilitation the frequency of malnutrition ranged from 30% to 49% in four trials (Aquilani et al. 1999; Finestone et al. 1995; Hama et al. 2005; Poels et al. 2006).
Conclusions Regarding the Incidence of Malnutrition The incidence of malnutrition varies from 6% to 62% post stroke, depending on the timing of assessment and the criteria used to define malnutrition.
There is no “gold standard” for the assessment of nutritional status.
Malnutrition is a relatively common problem post stroke.
16.3 Factors Associated With the Development of Malnutrition
Malnutrition in any disease state develops over a period of time as a result of either increased metabolism/catabolism or inadequate nutritional intake. There may be occasions when these two factors are superimposed. The development of malnutrition may also be hastened if the
Figure 16.1 Prevalence of Malnutrition Following Stroke
The prevalence of malnutrition post stroke can vary widely depending on the criteria used to define it and the point at which it is measured. Among the studies represented below, the number of values, which fell below normal reference ranges, varied from 1 to 3 and the total number of parameters assessed ranged from 2 to 9. In some cases the reference criterion was grouped according to age or sex, while in other studies, single cut-off values were used.
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gastrointestinal tract is compromised and nutrient absorption is impaired. The evidence with respect to the potential contributions of these mechanisms is reviewed.
16.3.1 Hypermetabolism Following Stroke Hypermetabolism has been defined as an increase in metabolic rate above that which is predicted using equations accounting for age, sex, height and weight (Souba & Wilmore 1999). Elevated metabolic rates of 140-200% above predicted values have been well described for some disease states including burns, sepsis (Long 1984) and head injury (Young et al. 1992) and are reflective of increased oxygen consumption associated with injury severity. It appears that stroke results in similar metabolic perturbations, although the effect may not be as pronounced. Although 5 studies have examined the metabolic rate following “stroke”, collectively, the results are difficult to interpret. Patients with severe stroke (including infarct, SAH and intracerebral hemorrhage) who were mechanically ventilated, some of whom were sedated, were included in three of the studies. The percentage increase above predicted levels was reported in only 1 of these studies. Only two studies have been conducted to measure the resting energy expenditure of non-ventilated patients following uncomplicated stroke. In these studies metabolic rate was measured at a point beyond 7 days, in a non-ICU setting. Evidence from these 2 studies suggests that stroke patients are mildly hypermetabolic and are not at an increased risk for the development of malnutrition due to the effects of hypermetabolism (see Table 16.4).
Author/Year/ Country
Methods Outcome
Weekes and Elia (1992) UK No Score
Resting energy expenditure of 15 patients was measured 24-72 hrs post stroke. Measurements were repeated in 11 of the patients 10-14 days later.
No evidence of hypermetabolism at either of the study points. Metabolic rate was 107% of predicted values. No significant differences between the first or second measurement.
Finestone et al. (2003) Canada No Score
Resting energy expenditure (REE) of 91 stoke patients were measured at admission to hospital, and on days 7, 11, 14, 21 and 90. Comparisons were made with 10 healthy volunteers of similar ages.
The mean REE of stroke patients ranged from 1521-1663 Kcals/day. This represented 107-114% of the predicted expenditure, estimated by the Harris-Benedict equation. The REE of controls was similar to that of stroke patients.
Bardutzky et al. (2004) Germany No Score
The metabolic rates of 34 sedated and mechanically ventilated patients with severe stroke were measured during the first 5 days of injury. The metabolic rates of patients with spontaneous ICH (n=13) and MCA infarction (n=21) were compared.
Over the study period the metabolic rates of patients with ICH varied from 1,570- 1,623 kcals/day, compared with 1,560 and 1610 kcals/day for patients with infarction. The differences were not statistically significant. All measurements correlated strongly with estimated REE using the Harris-Benedict equation.
Esper et al. (2006) USA No Score
The resting metabolic rates of 14 mechanically ventilated patients with non-traumatic intracerebral (ICH), intraventricular (IVH) or subarachnoid hemorrhage (SAH) were compared with 6 patients with traumatic brain injury (TBI), retrospectively. Indirect calorimetry was conducted within 7 days of injury/ ictus.
No patient was pharmacologically paralyzed. Median REE was 1810 (1124-2806) and 2238 (1860-2780) kcal/d for the non-traumatic group and TBI group, respectively. The increase above predicted values using the Harris-Benedict equation was 126% (non-traumatic) and 147% (TBI). The differences between groups were not statistically significantly.
Frankenfield and Ashcraft (2012) USA No Score
Indirect calorimetry was conducted prospectively in 130 mechanically ventilated patients within the first 6 days of admission to a critical care unit owing to
Compared with other groups, patients with IS had significantly lower metabolic rates: (1,879 kcal/d vs. 2,047 (HS) vs. 2,099 (ITBI) vs. 2,127 (TBI+). Using the Penn State prediction equation,
Table 16.4 Studies Examining Resting Energy Expenditure Post Stroke
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ischemic stroke (IS), hemorrhagic stroke (HS), isolated traumatic brain injury (ITBI), or traumatic brain injury with collateral injuries (TBI+).
patients with IS had metabolic rates >15% of predicted values in 60% of cases, compared with 74% to 86% of the other 3 types of injury. However, all of the differences in metabolic rates were eliminated after controlling for maximum body temperature and minute ventilation.
Conclusion Regarding Hypermetabolism Post Stroke There is an elevation in metabolic rate following stroke that ranges from 107% above predicted levels to 126%. There is conflicting evidence that metabolic rate is elevated more in hemorrhagic stroke compared with ischemic stroke.
Patients are not hypermetabolic acutely following stroke.
16.3.2 Increased Catabolism Following Stroke Increases in both metabolic rate and catabolism post-injury have been attributed to the effects of the acute phase response, mediated largely through the effects of cytokines and counter-regulatory hormones, following injury or disease (Staal-van den Brekel et al. 1995; Young et al. 1985). Elevations of peripheral plasma catecholamines, cortisol, glucagons, IL-6, IL-1RA and acute phase proteins have been well described following stroke (Beamer et al. 1995; Fassbender et al. 1994a; Fassbender et al. 1994b; Ferrarese et al. 1999; Muir et al. 1999; Murros et al. 1993; Syrjanen et al. 1989) (see Table 16.5). Prolonged elevations of these compounds may lead to the depletion of lean body mass (muscle) and fat, which may contribute to the development of malnutrition.
Table 16.5 Studies Reporting Elevations of Acute Phase Reactants Following Stroke
Author/Year Country
“n” Time Studied Post Stroke Indicator/Response
Syrjanen et al. 1989 Finland
50 Within 72 hrs CRP ()
SAA ()
ACT ()
Murros et al. 1993 Finland
105 (ischemic stroke) 3 days and 1 week Cortisol ()
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Scotland
CRP (C-reactive protein) IL-1ß (Interleukin-1ß) SAA (serum amyloid A protein) IL-6 (Interleukin-6) ACT ( α-antichymotrypsin) IL-1RA (Interleukin-1 receptor antagonist) ACTH (adrenocorticotropic hormone) (-) indicates no change TNF (tumor necrosis factor)
Conclusions Regarding an Acute Phase Response Following Stroke Although there is evidence that an acute phase response accompanies stroke, its contribution to the development of malnutrition remains unclear.
16.3.3 Gastrointestinal Function Following Stroke The major effect on the gastrointestinal tract following stroke is impairment of oral, pharyngeal and esophageal functions, manifested as dysphagia (see Chapter 15. Dysphagia and Aspiration). Dysphagia may resolve spontaneously in the days following stroke or persist for many months, even years. For a minority of patients severe dysphagia will preclude safe oral feeding and alternative strategies will be required. The association between dysphagia and malnutrition was examined in three studies. The results are presented in Figure 16.2. The odds of developing malnutrition increased significantly following acute hospital admission at both one week following stroke and upon admission to an inpatient rehabilitation unit (approximately 3 weeks post stroke). Although the mechanism was not explored, decreased intake or delayed enteral feeding may have contributed to declines in nutritional status. At admission to hospital, shortly following stroke onset nutritional status was unrelated to the presence of dysphagia (Crary et al. 2006; Crary et al. 2013; Davalos et al. 1996). Crary et al. did report a relationship between the presence of dysphagia and dehydration at both hospital admission and at day 7 following stroke (Crary et al. 2013). Other significant gastrointestinal impairments have not been reported. Although stroke patients do not appear to be at increased risk for stress ulcer formation or gastric bleeding (Ullman & Reding 1996), anticoagulation therapy may increase the risk. Gastric motility could be theoretically altered, since it is modulated through the central nervous system. However, there is no evidence to suggest that this is the case. Although constipation is a frequently cited complaint following stroke, this is thought to be due to a variety of factors, arising secondary to stroke, including reduced mobility, decreased fluid intake and medication usage. Stroke per se is not known to cause constipation (Johanson et al. 1992; Sonnenberg et al. 1994). There is no evidence to suggest that nutrient absorption is impaired following a stroke.
Conclusions Regarding the Alteration of Gastrointestinal Function Following Stroke
There is an absence of literature to confirm or refute whether the significant gastrointestinal impairments develop following stroke.
Figure 16.2 The Association Between Dysphagia and the Development of Malnutrition
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16.3.4 Nutrient Intake Following Stroke Stroke patients may be particularly vulnerable to protein-energy malnutrition due to a variety of factors that affect their willingness or ability to self-feed, such as loss of appetite associated with depression, cognitive deficits, dysphagia (difficulty swallowing), visual neglect, upper extremity paresis, and apraxia (an inability to use objects correctly) (Finestone et al. 2003). However, few studies exist that describe the energy and protein intakes of hospitalized stroke patients. Gariballa et al. reported that the average two-week energy intake of stroke patients who did not have swallowing difficulty following stroke and who consumed a regular hospital diet was 1338 kilocalories (Kcals) representing 74 percent of their predicted requirement (Gariballa 2001). This level of adequacy was not significantly different from 42 age- and sex-matched nonstroke patients who consumed 1317 Kcals, or 73 percent of requirement, suggesting that the intakes of stroke patients were similar to those of other hospitalized patients. The only other study which examined protein and energy intakes following stroke reported that, on average, regardless of diet type (oral or non-oral) and texture (regular diet or texture-modified because of swallowing impairment), hospitalized patients consumed an average of 85 percent of their energy requirements, and 86 percent of protein requirements, during the first 21 days following stroke (Foley et al. 2006).
Conclusions Regarding Nutrient Intake Following Stroke Stroke patients consume between 74 and 86% of their energy and protein requirements during the first several weeks following stroke.
Patients consume fewer calories and protein following stroke.
16.3.5 Stroke-Related Factors A variety of stroke-related deficits may impair the patients’ ability to self-feed. Some of these factors include upper extremity paresis, apraxia, visual and cognitive, perceptual deficits such as visual neglect. Voluntary reduced food intake may also result from depression associated with stroke.
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Nutrition interventions associated with stroke are usually directed at the improvement of nutrient intakes through i) oral supplementation, ii) enteral feeding or iii) dysphagia therapy. The goal of all nutritional interventions is the prevention or correction of “malnutrition”.
16.4.1 Enteral Feeding Enteral feeding may represent a sole or supplemental source of feeding. Generally, enteral nutrition as the sole source of nutrient intake is reserved for dysphagic patients for whom oral feeding is considered unsafe. However, “failure to thrive” non-dysphagic stroke patients may also be candidates for enteral feeding in the presence of prolonged and inadequate oral intake. The use of feeding tubes in these stroke patients has been shown to reverse malnutrition (Finestone et al. 1995). Therefore, the use of feeding tubes can prevent or reverse the effects of malnutrition in patients who are unable to safely eat and those who may be unwilling to eat. Data from the Post-Stroke Rehabilitation Outcomes Project (James et al. 2005), which retrospectively studied the outcomes of 919 patients from six inpatient rehabilitation sites, provides evidence that tube feeding is an effective intervention. Patients with both moderate and severe stroke who had received tube feeding during hospital stay but who were not discharged with a feeding tube in place achieved greater increases in total FIM gains and experienced greater improvement in severity of illness by discharge. Among 143 patients admitted to an inpatient rehabilitation facility with an enteral feeding tube in place due to dysphagia, 20% were able to have their tubes removed prior to discharge, having resumed full oral intake (Krieger et al. 2010). Sixty-five percent were able to return to some type of oral feeding prior to discharge. Patients who were able to have their FT removed were more likely to be discharged to home. Nakajima et al. reported that of a cohort of 4,972 consecutively admitted ischemic stroke patients, 723 (14.5%) could not eat orally on day 10 post stroke (Nakajima et al. 2012). Of the 512 dysphagic patients who responded to a questionnaire at 3 months, 141 (27%) had resumed oral intake. An NIHSS score of ≤17 on day 10 was the strongest predictor or ability to eat orally at 3 months. NIHSS scores as well as the presence of bihemisperic lesions were found to be the most predictive factors for PEG placement among a group of 77 stroke patients following severe stroke (Kumar et al. 2012). Many feeding tube types and procedures are available. In cases where enteral tube feedings are indicated, this can be achieved through either a temporary or permanent access. A nasogastric (NG) feeding tube is often placed in patients who are expected to return to a full oral diet within one month. There is consensus opinion that permanent feeding access is indicated when a prolonged period of non-oral intake (>1 month) is anticipated (Committee 1995). Examples of available techniques include percutaneous gastrostomy/jejunostomy (endoscopically or radiologically inserted), percutaneous gastrojejunostomy (endoscopically or radiologically inserted) and surgically placed gastrostomy/ jejunostomy. In Canada, a greater percentage of feeding tubes are placed by radiologists compared to gastroenterologists. The differences may be due to issues of financial remuneration, availability of facilities and technical expertise. Surgically placed feeding tubes are uncommon in the stroke patient population. Controversy continues as to whether placement of the feeding tube into the small bowel reduces the risk of aspiration (see Chapter 15. Dysphagia and Aspiration). Therefore, placement of feeding tubes into the stomach and the small bowel are both commonly employed in dysphagic stroke patients.
Author, Year Country
PEDro Score
Methods Outcomes
Park et al. (1992)
40 patients (18 with stroke) with long-standing dysphagia randomized to receive either a
Treatment failure, including blocked and dislodged tubes occurred in 18/19 patients in
Table 16.6 Efficacy of Enteral Feeding Post Stroke
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Scotland 6 (RCT)
percutaneous endoscopic gastrojejunostomy (PEG) or a nasogastric tube (NG) for 28 days of enteral feeding.
NG group compared to 0/19 in PEG group. Patients in NG group received significantly less volume of feed compared to PEG group (55% vs. 93%).
Norton et al. (1996) UK 6 (RCT)
30 dysphagic patients were randomized to receive either a gastrostomy (G) feeding tube or nasogastric (NG) feeding tube for enteral feeding at 14 days post stroke.
At 6 weeks, a significantly greater proportion of patients had died in the NG group compared to patients in the G group (2 vs 8). Patients in the G group had better nutritional indices including weight, serum albumin, mid-arm circumference. There were no omitted feeds among patients in the G group compared to at least one missed feed in 10 patients in the NG group.
Nyswonger and Helmchen (1992) USA No Score
The charts of 52 stroke patients admitted between 1988 and 1991 who received enteral nutrition as inpatients were reviewed. Patients were grouped according to lag in feeding time from admission to tube insertion (< or > 72 hours).
Patients who had been enterally fed within 72 hours of admission had significantly shorter hospital length of stay compared to those who were fed > 72 hours of admission (20.14 ± 13 vs. 29.76 ± 20days, p<0.05)
Dennis et al. (2005a) UK 8 (RCT)
This study was one branch of a RCT evaluating 3 distinct nutritional interventions. 859 acute stroke patients with dysphagia were randomized to receive early enteral feeding vs. delayed. The outcome of death or disability was evaluated at 6 months.
Early tube feeding was associated with an absolute reduction in risk of death of 5.8% (95% CI -0.8 to 12.5, p=0.09) and a reduction in death or poor outcome of 1.2% (-4.2 to 6.6, p=0.7)
Dennis et al. (2005b) UK 8 (RCT)
This study was one branch of a RCT evaluating 3 distinct nutritional interventions. 321 acute stroke patients with dysphagia were randomized to receive a nasogastric (NG) tube or a percutaneous endoscopic gastrostomy (PEG) tube for enteral feeding. The outcome of death or disability was evaluated at 6 months.
In the PEG versus nasogastric tube trial, 321 patients were enrolled by 47 hospitals in 11 countries. PEG feeding was associated with an absolute increase in risk of death of 1.0% (-10.0 to 11.9, p=0.9) and an increased risk of death or poor outcome of 7.8% (0.0 to 15.5, p=0.05).
Hamidon et al. (2006) Malaysia 6 (RCT)
23 consecutive inpatients admitted with acute ischemic stroke were randomized to receive either an NG or PEG feeding tube. At baseline and 4 weeks follow-up the following assessments were conducted: tricep skinfold (TSF), bicep skinfold (BSF), mid-arm circumference (MAC), serum albumin, treatment failure, defined as persistent blocked or dislodged tubes.
At the end of four weeks, subjects in the PEG group had significant increase in the median serum albumin values compared with baseline, whereas subjects in the NG group experienced a decrease (+2.5 vs. -5.0 g/L, p=0.045). There were more treatment failures in the NG group (5/10 vs. 0/8, p=0.036). There were no other significant differences between groups.
There have been only four RCTs that have addressed the issue of enteral feeding in stroke patients. All of these trials examined the differences in outcomes of patients with two different types of feeding tubes-PEG vs. NG tubes. Park et al. randomized a neurologically heterogeneous group of 40 dysphagic patients (45% with stroke) to receive either a percutaneous endoscopic gastrostomy (PEG) or nasogastric (NG) tube for 4 weeks of enteral feeding (Park et al. 1992). There was a higher number of treatment failures associated with the NG tube group while patients in the PEG group received significantly greater proportion of their prescribed feeds. Hamidon et al. also reported a higher number of treatment failures in patients fed using NG tubes (Hamidon et al. 2006). The same authors also reported a significant difference in serum albumin values, favouring the PEG group; however there was
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a difference in the baseline values, suggesting the possibility of a biased treatment effect (PEG group: 37.0 g/l, NG group 37.0 g/l). A study by Norton et al. randomized 30 stroke patients to receive either a gastrostomy tube or NG tube for enteral feeding (Norton et al. 1996). A significantly greater number of patients in the NG group had died at six weeks. The authors concluded that based on the results of this study that PEG tubes were the preferred method of feeding stroke patients unable to eat orally. However, this finding suggests an imbalance in the prognostic profiles at entry. Although patients were randomly assigned to the two treatment groups and had similar Barthel Index score (<3 for both groups), there may have been other important differences between groups. Several factors suggest that these two groups may had been clinically quite different: 1) half of the patients who died in the NG group died of complications attributed to the original stroke suggesting that these patients had more severe strokes, 2) none of the patients in the NG group recovered their swallowing function by the end of follow-up, whereas all of the patients in the gastrostomy fed group had their feeding tubes removed and resumed normal oral intake, 3) at six weeks, none of the patients in the NG group had been discharged, compared to all of the patients in the gastrostomy fed group (who were discharged to nursing homes, 4) there are known floor and ceiling effects associated with the Barthel Index, which would not be sensitive enough to capture even clinically significant differences in impairment status and 5) the Barthel Index was used as a proxy for stroke severity. More recently Dennis et al. randomized a large number of patients to receive either a NG or PEG type feeding tube (Dennis et al. 2005a). Large sample sizes, strong methodology, clinically relevant outcomes and nearly complete follow-up set this inter-related family of trials apart from its predecessors. The results did not support the purported benefits of PEG tubes reported from previous studies. In fact, a greater proportion of patients fed with a PEG feeding tube were either dead or dependent at 6 months. The result approached statistical significance (p=0.05). However, the volume of tube feed formula that patients received over the study period in the FOOD trial was not reported and, potentially, it may not have been comparable between the groups. Although the reason for the negative result is unclear, the authors speculate that differences in nursing interventions may be contributory. Within the same trial, a delay (>7 days) in initiating enteral feeding was not statistically associated with a worse outcome, compared to early feeding within 72 hours of admission. While mortality risk was assessed in four studies, results could be estimated in two (Dennis et al. 2005a; Norton et al. 1996). The results from the FOOD trial heavily influenced the results of the pooled analysis. There was no increased risk of either mortality or poor outcome associated with feeding tube type (NG vs. PEG). Figure 16.3
Conclusions Regarding the Use of Enteric Feeding Tubes Based on the results of two RCTs of good quality, there is strong (Level 1a) evidence that intragastric feeding is associated with fewer mechanical complications compared to nasogastric feeding for stroke patients who require long term (>28 days) non-oral feeding. Based on the results from a single RCT, in which the results approached statistical significance, there is moderate (Level 1b) evidence that type of feeding tube (NG vs. PEG) is unrelated to death and dependency at 6 months.
Intragastric feeding tubes are associated with fewer complications compared with naso-enteric tubes when patients require nutritional support for at least 28 days.
Figure 16.3 Outcomes Evaluating NG vs. PEG Feeding Routes
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16.4.2 Oral Supplementation Oral supplementation may be indicated for patients who are safe with oral intake, but who fail to take in sufficient quantities to meet their nutritional requirements and/or for patients with pre-existing nutritional deficits. Theoretically, oral supplementation could be effectively used to improve nutritional intake, which would in turn lead to improvements in nutritional parameters and ultimately functional outcome. In a review focusing on the treatment of protein-energy malnutrition in chronic non-malignant disorders, Akner and Cederholm identified three RCTs that included treatment for both dysphagic and non-dysphagic stroke patients (Akner & Cederholm 2001; DePippo et al. 1994; Gariballa et al. 1998b; Norton et al. 1996). Four “uncontrolled trials” were also identified (Davalos et al. 1996; Elmstahl et al. 1999; Nyswonger & Helmchen 1992; Wanklyn et al. 1995). These authors concluded that the treatment efficacy of protein energy malnutrition treatments could not be measured due to a “striking lack of published articles”.
Author, Year Country
PEDro Score
Methods Outcomes
Gariballa et al. (1998b) UK 6 (RCT)
42 malnourished stroke patients were randomized to receive a standard hospital diet or a standard diet plus an oral supplement supplying an additional 1200Kcals, 40g protein daily for 4 weeks.
Energy and protein intakes were higher in the supplemented group (1807 vs. 1084 kcals, 65.1 vs. 44.1 g protein). Patients in the supplemented group experienced less of a decline in serum albumin (–1.5 vs. -4.4g/L) and an improvement in serum iron levels (2.6
vs. –2.7 mol/L) compared to patients in the unsupplemented group.
Dennis et al. (2005b) UK 8 (RCT)
This study was one branch of a RCT evaluating 3 distinct nutritional interventions. 4,023 acute stroke patients without dysphagia were randomized to receive an oral nutritional supplement (540 Kcals) in addition to a hospital diet, provided for the duration of their entire hospital stay. The outcome of death or disability was evaluated at 6 months.
8% of patients were judged to be undernourished at baseline. Supplemented diet was associated with an absolute reduction in risk of death of 0.7% (95% CI -1.4 to 2.7) and an increased risk of death or poor outcome of 0.7% (-2.3 to 3.8). The result was compatible with a 1% or 2% absolute benefit or harm from oral supplements.
Aquilani et al. 48 patients with subacute stroke (14 days or more The mean MMSE scores before and after
Table 16.7 Efficacy of Oral Supplementation Post Stroke
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(2008a)a Italy 6 (RCT)
from onset) admitted for inpatient rehabilitation were randomized to receive daily supplementation providing an additional 250 kcal + 20 g protein or to regular diet alone for 21 days. The primary outcome measure was the Mini-Mental State Examination (MMSE) assessed before and after treatment.
treatment for were: experimental group 16.4 to 20.3 and control group 18.4 to 19.2. The difference between groups was not significant. The difference between groups when using the log transformed values of the MMSE were statistically significant.
Aquilani et al. (2008b)b Italy 6 (RCT)
42 patients admitted for inpatient rehabilitation an average of 16 days following acute stroke were randomly allocated to receive 21 days of protein supplementation (n=21) or regular diet (n=21) in order to investigate the recovery of neurological changes, measured using the National Institute of Health Stroke Scale (NIHSS).
At the end of the study period, the mean NIHSS scores had improved significantly more for patients in the supplemented group (-4.4 +/- 1.5 score versus -3 +/- 1.4 of control group; P<0.01).
Rabadi et al. (2008) USA 9 (RCT)
102 stroke patients admitted for inpatient rehabilitation within 4 weeks of onset and who had lost 2.5% of their pre-stroke weight during the acute admission period were randomized to receive a either a regular supplement (381 Kcals, 15 g protein) or intensive supplement (720 Kcals, 33 g protein) daily throughout their hospital stay. The primary outcome was FIM, assessed before and after treatment. The secondary outcome measurements included the FIM motor and cognitive subscores, length of stay (taken from day of admission), 2-minute and 6-minute timed walk tests measured at admission and on discharge, and discharge disposition (home/not home).
Patients receiving intensive nutritional supplementation improved more than those on standard nutritional supplements on measures of motor function (total FIM, FIM motor subscore, 2-minute and 6-minute timed walk tests, all significant at p < 0.002). The difference in FIM change scores was 31.5 (intensive group) vs. 22.9 (regular group). They did not, however, improve on measures of cognition (FIM cognition score). A higher proportion of patients who received the intensive nutritional supplementation went home compared to those on standard supplementation (43% vs. 63%, p = 0.05).
Ha et al. (2010b) Norway 5 (RCT)
Acute stroke patients (malnourished or at nutritional risk) were randomized to receive either individualized, nutritional care to prevent weight loss (n=58) or routine care (n=66) while in hospital. Primary outcome measure was the percentage of patients with weight loss >/=5% at 3 months. Secondary outcomes measures were quality of life (QoL), handgrip strength and length of hospital stay.
During hospitalization, patients in the intervention group consumed significantly more energy, but not protein, compared with patients in the control group. At 3 months, 20.7% of the patients in the intervention group had lost ≥5% weight compared with 36.4% of patients in the control (p=0.055). Patients in the intervention group had a significantly higher QoL scores (P = 0.009) and greater handgrip strength (P = 0.002). Length of hospital stays were similar between groups (median of 12 vs. 13 days).
Ha et al. (2010a) Norway 5 (RCT)
Additional analyses from 2010a) study assessing body composition.
At 3 months, men and women in both groups had experienced weight loss. Whereas there were no differences in any of the body composition outcomes between the groups in men (weight, BMI, MAUC, TSF or AMC), women in the intervention group lost less weight (P = 0.022) and fat (P = 0.005) compared with the controls.
Dennis et al. (2005) routinely randomized all non-dysphagic patients, regardless of their nutritional status to receive a daily oral supplement, which contained 2,257 kJ (or 540 Kcals/day) and 22.5 g protein until discharge, in addition to a regular diet, or to regular diet alone (Dennis et al. 2005b). There were no differences in the proportion of patients who were dead or dead/disabled (defined as a Modified Rankin
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Score of 3-5) at six months. The percentage of patients in each group who had experienced death or poor outcome was identical between groups (59%). The odds of death or poor outcome were reduced for the 8% of undernourished patients (presumably patients who would benefit the most from treatment) receiving supplementation, although the results did not reach statistical significance. Theoretically, oral supplementation should increase the likelihood that patients will consume sufficient energy and protein to meet their actual requirements. However, both under-feeding and over-feeding can still result and neither condition would be expected to improve outcome. No indication of actual nutrient intake or its relationship to estimated nutrient requirement is provided, although the authors do note this as a limitation of the study. Gariballa et al. (1998b) selectively randomized only patients considered to be malnourished to receive an oral supplement in addition to regular diet, or to regular diet alone (Gariballa et al. 1998b). Although they reported significant changes in two nutritional parameters at follow-up, albumin and iron, there were no differences between the groups in terms of non-nutrition outcome measures including Barthel Index scores, infective complications and length of hospital stay and mortality (see Figures 16.4). There may be several reasons for the null result. The length of the intervention period could have affected the magnitude of the observed effect sizes. Perhaps a longer period of study is required to fully elucidate the effects of poor intake on function. Given that malnutrition is a condition that develops over time, it is unclear how long poor intake needs to continue before declines of nutritional markers will be manifested as increased morbidity and mortality and declines of functional outcomes. The Barthel Index may not be a sensitive enough measure to capture clinically significant changes in functional outcome. Patients in this study were considered to be malnourished if both tricep skinfold measurements (TSF)
and midarm circumference (MAC) were 1 SD of reference norms. While these criteria would definitely favour the identification of slim individuals as malnourished, it may not necessarily have selected only those who were truly malnourished. Nutritional supplementation may fail to improve outcome indicators or markers of nutritional status in well-nourished individuals. Aquilani et al. (2008a) examined the potential benefit of oral supplementation to enhance cognitive recovery following stroke (Aquilani et al. 2008a). The authors hypothesized that, among other mechanisms, the additional supply of amino acids could help to re-activate the synthesis of neural proteins, thereby increasing neuron energy and neurotransmitter function. Although the authors stated that the treatment was successful as demonstrated by a significantly greater improvement in MMSE scores over the study period, it should be noted that the MMSE is a screening tool and was never intended to be used to assess responsiveness to treatment. Furthermore, there were statistically significant differences in the baseline MMSE scores between treatment and control groups, which were not adjusted for in their analysis. In a related study Aquilani et al. demonstrated that 3 weeks of a protein-supplemented diet resulted in greater neurological recover, measured by the NIHSS scale (Aquilani et al. 2008b). The authors suggested that increased protein synthesis could “induce axonal sprouting and formation of new cortical connections” in both perilesionsal and remote areas of the brain and may also improve training-induced plasticity. Rabadi et al. (2008) randomized stroke patients who they determined to have experienced significant weight loss over a 2-week period to receive either routine of intensive oral supplementation for the duration of their hospital stay (Rabadi et al. 2008). Although the authors reported that there were significantly greater improvements in FIM scores experienced by the intensive group, the generalizability of their findings is questionable. Stroke severity was measured using the MMSE, not by a scale designed to measure severity. Therefore, potential baseline differences between groups remain unknown. Also, while the volumes, protein, energy content and compliance with supplement use is reported, the
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authors provide no data on actual caloric intake over the study period. There were no significant changes in nutritional indicators (weight, serum albumin, pre-albumin or transferin) between groups. Ha et al. (2010a) examined whether an individualized nutritional program including oral sip supplementation during hospitalization in the acute stage of stroke could prevent or minimize weight loss at 3 months (Ha et al. 2010a). Although there was no statistically significance difference in the proportion of patients who lost 5% of more of their weight, the authors thought that the mere completion of diet records for patients in the control group increased aware of, and attention to, adequacy of energy intake. In a separate analysis excluding the 38 control group patients for whom dietary records had been kept, revealed a significantly lower proportion of patients in the intervention group who had dropped 5% of body weight (20.7% vs. 42.9%, p=0.032). Woman appeared to benefit preferentially from the treatment and experienced less weight loss and reductions in fat stores compared with men (Ha et al. 2010b). The pooled outcomes of mortality and death/poor outcome associated with oral supplementation are presented in Figure 16.4. There was no protective effect association with supplementation on either outcome.
Conclusions Regarding Oral Supplementation
There is conflicting (Level 4) evidence that oral sip supplementation improves functional outcomes in stroke patients. Based on the results from a single RCT, there is moderate (Level 1b) evidence that routine oral sip supplementation does not reduce the incidence of death or dependency following stroke. There is moderate (Level 1b) evidence that oral supplementation improves the energy and protein intakes of stroke patients. There is moderate (Level 1b) evidence that oral supplementation improves the nutritional parameters of stroke patients.
Figure 16.4. The Effectiveness of Oral Supplementation
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Oral supplementation improves energy and protein intake although it may not necessarily improve functional outcomes.
16.4.3 Dysphagia Treatment Several studies have examined the use of dysphagia treatment programs to improve the nutritional status of patients post stroke. The results from these trials can be used to inform treatment decisions.
Author, Year Country
PEDro Score
Methods Outcomes
DePippo et al. (1994) USA 5 (RCT)
115 patients randomized to receive either one formal dysphagia treatment session and choice of modified-texture diet, one dysphagia session with prescribed texture-modified diet or daily intervention by SLP and prescribed diet.
During inpatient rehabilitation stay, there were no differences in proportions of patients developing “calorie-nitrogen deficit” between the 3 groups. 7 patients in total (6%) were classified as malnourished.
Elmstahl et al. (1999) Sweden No Score (cohort)
38 dysphagic stroke patients received dysphagia therapy for approximately 2 months, which included oral motor exercises, swallowing techniques, positioning and dietary modifications.
Albumin and total iron-binding capacity (TIBC) increased significantly following treatment. The percentage of patients with albumin and TIBC below normal levels decreased from 72% to 42% and 50% to 19%, respectively.
Lin et al. (2003) Taiwan No Score
A quasi-experimental parallel, cluster design study that recruited 61 patients (2:1) from 7 long-term care facilities to receive either swallowing training or no therapy (Patients received therapy following data collection). Swallowing training consisted of direct therapies (compensatory strategies, diet modification, environmental arrangement, the Mendelssohn maneuver, supraglottic swallowing and effortful swallowing) and indirect therapies (thermal stimulation, oral motor and lingual exercises and were provided 30 min/days 6 days/week x 8 weeks.
The results of between group comparisons on change scores (pre-test, post test) showed statistically significant improvements favouring the treatment group for: swallowing function (incidence of coughing/choking, volume/second swallowed, volume per swallow), neurological examination and nutrition parameters (mid-arm circumference and weight)
Carnaby et al. (2006) USA 8 (RCT)
306 patients with clinical dysphagia admitted to hospital with acute stroke were randomly assigned to receive usual care (n=102), standard low-intensity intervention (n=102), or standard high-intensity intervention and dietary prescription (n=102). Treatment continued for up to a month. The primary outcome measure was survival free of an abnormal diet at 6 months
Of patients randomly allocated usual care, 56% (57/102) survived at 6 months free of a modified diet compared with 64% (65/102) allocated to standard (low-intensity) swallowing therapy and 70% (71/102) patients who received high-intensity swallowing therapy. Compared with usual care and low-intensity therapy, high-intensity therapy was associated with an increased proportion of patients who returned to a normal diet (p=0.04) and recovered swallowing (p=0.02) by 6 months.
Three studies have examined the impact of formal dysphagia therapy on nutritional status, although nutritional indicators were the secondary end points in all of the studies and not the primary focus of the trial. DePippo et al. (1994) conducted the only RCT of formal dysphagia therapy, which demonstrated no benefit of treatment (DePippo et al. 1994). There were no differences in the
Table 16.8 Efficacy of Dysphagia Treatment Programs
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percentage of patients classified as suffering from calorie-nitrogen between treatment groups at the end of the follow-up period (Figure 16.5). To enable pooling of results two groups, which provided varying levels of involvement with a Speech-Language Pathologist (SLP) were combined and compared to a group where SLP involvement was minimal and dysphagic patients, were free to choose their diet. However, the two-week treatment period may have been too short to actually demonstrate a significant difference. Lin et al. (2003) also reported improvements in various nutrition parameters and choking frequency among patients who participated in a swallowing training program (Lin et al. 2003). Elmstahl et al. (1999) reported that 38 patients who received two months of dysphagia therapy experienced significant increases in two nutrition indicators (Elmstahl et al. 1999). DePippo et al. (1994) failed to report a difference in the outcome of malnutrition, as defined by nitrogen deficit when assessing the efficacy of dysphagia therapy across three treatment arms (Figure 16.6) (DePippo et al. 1994). The negative result may have been the result of a true lack of effect of therapy, or it could be that the intervention was not provided for a sufficient length of time to reveal an observable effect. Carnaby-Mann et al. (2005) found a trend towards statistical significance when examining the impact of two levels of dysphagia treatment programs (low and high intensity) on decreasing the need for a modified diet (Carnaby-Mann & Crary 2005). Compared to usual care, patients who received instruction on compensatory swallowing strategies, swallowing exercises and regular re-evaluation of dietary modifications were more likely to have returned to an unmodified diet at six months.
Conclusions Regarding the Efficacy of Dysphagia Treatment Based on the results from a single RCT, there is moderate (Level 1b) evidence that that dysphagia therapy does not prevent the development of malnutrition.
16.4.4 Effect of Nutritional Interventions on Changes in Nutritional Parameters The results from trials, which assessed changes in nutritional parameters following any form of nutritional intervention, were pooled. The results are presented in Figure 16.6. The following outcomes were assessed:
1. Changes in serum albumin concentration
Figure 16.5 The Effectiveness of Dysphagia Therapy
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2. Changes in weight 3. Changes in mid-arm circumference 4. Changes in triceps skinfold measurement
Sufficient data was presented in the four studies to enable either the generation of an unadjusted odds ratio or a weighted mean difference for at least one of the outcomes (DePippo et al. 1994; Gariballa et al. 1996; Norton et al. 1996; Park et al. 1992). (Nasogastric tubes were considered the control condition in studies assessing feeding tubes).
All three of the RCTs included in the pooled analysis reported a positive treatment effect associated with some form of nutritional intervention; all studies reported a significant improvement in serum albumin, mid-arm circumference and weight among patients in the treatment groups. Overall, there was a statistically significant improvement in nutrition markers following a period of nutritional intervention
(WMD: 2.44; 95% CI: 0.06-4.83), with significant heterogeneity (2 = 33.2, p< 0.00001, df=6). The heterogeneity could be explained by the differences in follow-up periods, interventions provided, sample sizes, (which ranged from 30-208) and the length of time the treatments were provided.
16.5 Enteral Feeding in the Community
There has been an increasing trend to place enteral feeding tubes in stroke patients who required long term, non-oral feeding. This has raised many ethical and practical issues surrounding feeding. Although
Figure 16.6 Changes in Nutritional Indices Associated with Nutritional Intervention
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there have been no RCTs published on the efficacy of long-term enteral feeding following stroke, there have been many cohort studies (see Table 16.9).
Author/Year/ Country
PEDro score
Methods Outcome
Wanklyn et al. (1995) UK No Score
Retrospective study of 41 stroke patients. (37 records were reviewed).
Median time to tube insertion was 26 days complications included 5 chest infections and 1 perforation. 57% of patients had died during their original hospital admission. 16% of patients were alive at 1 year. One patient experienced a good functional recovery.
James et al. (1998) UK No Score
Retrospective study of 126 stroke patients.
Median time to tube insertion was 22 days. 41 (33%) patients recovered their swallowing function. 63 (50%) patients experienced complications: aspiration pneumonia occurred in 22 (18%) patients. 47% of patients were alive at 1 year.
Wijdicks and McMahon (1999) USA No Score
Retrospective study of 63 stroke patients.
Median time to tube insertion was 11 days. 21 (33%) patients died. 36 (57%) remained severely disabled and institutionalized. PEGs were removed 2-36 months after placement in 18 patients. Aspiration pneumonia was reported in 4 (6%) patients transferred to nursing homes.
Callahan et al. (2000) USA No Score
Retrospective study of 150 patients aged 60 years (41% stroke patients).
72 patients were followed for 1 year (42% strokes). 50% of patients were alive at 1 year. 15% of patients were treated for pneumonia over the year. Of those surviving at least 60 days, 70% did not experience significant improvement in functional, nutritional or health status.
Sanders et al. (2000) UK No Score
Subset of 25 stroke patients from Norton et al. (1996) followed prospectively.
PEG tubes were placed 14 days following stroke. 64% of patients were alive at 6 months. 16% of patients had returned to oral intake at 20 weeks.
Elia et al. (2001) UK No Score
12,977 patients from 282 centres received a PEG tube between 1996-1999 (37% stroke patients).
92% were fed by gastrostomy tube. 70% of patients were alive at 1 year. 13% of patients had returned to oral feeding at 1 year. A complication rate of ~1% was reported.
Author/Year/ Country
PEDro score
Methods Outcome
Shah et al. (2012) Malaysia No Score
Prospective study of 140 patients (70 on NG tube feeding; 70 controls). Cases were recruited from residential homes or stroke daycare centres and were on NG tube feeding for at least 8 weeks.
64.3% of patients had at least one complication from NG feeding (tube dislodgment or insertion damage or aspiration). Nutritional status in this group was poor. Compared to patients with normal feeding, a greater percentage of patients on NG feeding were classified as severely malnourished (38.6%) and 71.4% of patients did not meet daily caloric requirements.
Table 16.9 Summary of Studies Evaluating Percutaneous Endoscopic Gastrostomy Tube Use
Table 16.10 Summary of Studies Evaluating Long-term Nasogastric Tube Use
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Conclusions Regarding the Use of Enteral Feeding in the Community On average, feeding tubes were placed within the first month following stroke. The one-year survival rate of patients with feeding tubes varied widely from 16% to 70%. Aspiration pneumonia was reported in 6-18% of patients with feeding tubes.
The one-year survival rate of patients with feeding tubes, discharged to the community varied widely following stroke.
16.6 Total Parenteral Nutrition (TPN)
TPN is a form of aggressive nutritional intervention usually reserved for patients with a non-functioning gastrointestinal tract. Unless a stroke patient presented with a pre-existing medical condition that precluded safe oral or enteral feeding, parenteral feeding would rarely be indicated. Examples of such a situation may include a dysphagic patient who had refused an enteral feeding device, in whom a central line had been placed for an unrelated purpose or a patient with inflammatory bowel disease, when enteral feeding may be contraindicated. As a result of the limited use of this feeding modality, there have been no studies investigating the efficacy of parenteral feeding post stroke.
Conclusions Regarding the Use of TPN There have been no studies that have evaluated the efficacy of TPN in the treatment of stroke patients.
The use of TPN has not been studied in the stroke population.
16.7 Cochrane Reviews of Nutritional Interventions Following Stroke
There is currently one Cochrane Review evaluating nutritional interventions following stroke. Table 6.11 provides a summary of this review.
Author, Year Country
Title
Methods
Results
Geeganage et al. (2012) U.K. Interventions for dysphagia and nutritional support in acute and subacute stroke
33 RCT’s were included in the review consisting of 6,779 patients. Studies Included: RCT’s assessing swallowing therapy, route of feeding, timing of feeding, fluid supplementation and/or nutritional supplementation. Patients Included: Acute and subacute, ischemic or hemorrhagic stroke.
Nutritional Therapies: PEG vs. NG (n=5 studies; 455 patients): Primary outcomes: no effect on death or dependency/disability. Secondary outcomes: fewer treatment failures (OR 0.09; 95% CI 0.01 to 0.51; P=0.007), higher concentrations of albumin (MD 4.92; 95% CI 0.19 to 9.65) for PEG vs. NG. No statistically significant differences between the groups were found for mid-arm circumference, pressure sores, case fatality,
Table 16.11 Summary of Cochrane Reviews for Nutritional Interventions Following Stroke
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Only results from the Nutritional therapies section are reported here (Refer to Chapter 15 for other results)
Time since stroke: <6 months Mean age of patients: 71 years
institutionalization, length of stay, infection or pneumonia, dysphagia, or weight. Timing of feeding: data from only one study. Fluid supplementation: data from only one study. Nutritional supplementation (n=8 studies; 4391 patients): Primary outcomes: no effect on death or dependency/disability. Secondary outcomes: fewer pressure sores (OR 0.56; CI 0.32 to 0.96; P=0.03), greater energy intake (MD 430.18; 95% CI 141.61 to 718.75; P=0.003), and greater protein intake (MD 17.28; 1.99 to 32.56; P=0.03). No statistically significant differences were found between groups for length of hospital stay or albumin concentrations.
Overall, the Cochrane review found no statistically significant evidence for decreases in death or dependency using nutritional interventions. However, the use of a PEG tube compared to a NG tube resulted in fewer treatment failures. Only single studies evaluated the timing of feeding and the effects of fluid supplementation. Nutritional supplementation resulted in fewer pressure sores and greater nutritional intake. Another non-stroke specific Cochrane review (Gomes et al. 2012) compared PEG to NG with respect to the number of intervention failures, patient nutritional status, mortality, complications, time on the intervention, quality of life, length of stay in hospital and economic outcomes. This review included several stroke specific studies (Bath et al. 2000; Dennis et al. 2005a; Hamidon et al. 2006; Norton et al. 1996; Park et al. 1992), similar to those included in the Cochrane by Geeganage and colleagues, and found similar results. PEG and NG did not differ significantly in terms of patient outcomes, however, the PEG was found to have fewer treatment failures.
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Summary
1. The incidence of malnutrition varies from 8 to 49% post stroke, depending on the timing of the assessment and the criteria used to define malnutrition.
2. There is no “gold standard” for the assessment of nutritional status.
3. There is an elevation in metabolic rate following stroke that ranges from 107% above predicted levels to 126%.
4. There is conflicting evidence that metabolic rate is elevated more in hemorrhagic stroke compared with ischemic stroke.
5. There is evidence that an acute phase response accompanies stroke, although its contribution to the development of malnutrition is unclear.
6. Although dysphagia is common, there is an absence of literature to confirm or refute the development of other significant gastrointestinal impairments following stroke.
7. Stroke patients consume between 74 and 86% of their energy requirements during the first 3 weeks post stroke.
8. There is strong (Level 1a) evidence that intragastric feeding is associated with fewer mechanical complications compared to nasogastric feeding for stroke patients who require long term (>28 days) non-oral feeding. Based on the results from a single RCT, in which the results approached statistical significance, there is moderate (Level 1b) evidence that type of feeding tube (NG vs. PEG) is unrelated to death and dependency at 6 months.
9. There is moderate (Level 1b) evidence that oral supplementation improves the energy and protein intakes of stroke patients. There is conflicting (Level 4) evidence that oral sip supplementation improves functional outcomes in stroke patients. Based on the results from a single RCT, there is moderate (Level 1b) evidence that routine oral sip supplementation does not reduce the incidence of death or dependency following stroke.
10. There is moderate (Level 1b) evidence that that dysphagia therapy does not prevent the development of malnutrition.
11. The one-year survival rate of patients with gastrostomy feeding tubes varies widely from 16% to 70%. On average, feeding tubes are placed within the first month following stroke. Aspiration pneumonia was reported in 6-18% of patients.
12. There is moderate (Level 1b) evidence that dysphagia therapy does not impact on nutritional status. However, the one RCT upon which this conclusion was based had small patient numbers and the treatment period was only two weeks.
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