Journal of Clinical Neuroscience xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Impact of early enteral nutrition on short term prognosis after acute stroke Tianheng Zheng a, Xinpu Zhu a, Huazheng Liang a,b, Haixia Huang a, Jiandao Yang a, Shaoshi Wang a,⇑ a b
Department of Neurology, Branch of the People’s First Hospital, 1878 North Sichuan Road, Hongkou District, Shanghai 200081, China Neuroscience Research Australia, Randwick, NSW, Australia
a r t i c l e
i n f o
Article history: Received 8 December 2014 Accepted 3 March 2015 Available online xxxx Keywords: Dysphagia Nutrition support Post stroke infection Short term prognosis Stroke
a b s t r a c t We hypothesized that early enteral nutritional support would improve the short term prognosis of acute stroke patients with dysphagia, demonstrated by lower malnutrition rates, lower complication rates, and lower National Institutes of Health Stroke Scale (NIHSS) scores at 90 days post stroke. Nutrition support is an essential element in the care of stroke patients and many studies have investigated the effect of specific nutritional elements on stroke patients. However, few studies have looked at the impact of complete enteral nutrition on Chinese patients with acute stroke. To investigate this, we conducted a randomized controlled trial of 146 patients with acute stroke and dysphagia, among whom 75 were supported with nasogastric nutrition and 71 received family managed nutrition after randomization. Nutritional status, nosocomial infection and mortality rates were recorded on day 21 of hospitalization. Neurological deficits were evaluated by the NIHSS activities of daily living Barthel index (ADLBI) and the modified Rankin scale (mRS) and compared between the two groups. We found that the nasogastric nutrition group had a better nutritional status and reduced nosocomial infection and mortality rates after 21 days compared with patients in the family managed nutrition group. In addition, the nasogastric nutrition group showed a lower score on the NIHSS than the control group. However, the differences in the scores of the ADLBI and the 90 day mRS between the groups were not significant. Taken together, the present study shows that early enteral nutrition support improves the short term prognosis of acute stroke patients with dysphagia. Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction Malnutrition is a potential complication during the rehabilitation of stroke patients. Its incidence varies from 6.1 to 62.0% among stroke patients due to the differences in methodologies and the time of evaluation of nutritional status [1]. It also increases the incidence of post stroke infection, recurrent stroke and mortality, resulting in a poor prognosis ([2]). It has been shown that the nutritional status of stroke patients is closely related to their long term clinical outcome [3]. Though a large number of studies have investigated the effect of specific nutrients on the recurrence of stroke such as vitamin B, folic acid ([4,5], antioxidants [6–8], and fat [9–12]), none have shown significant improvements in mortality and recurrence of stroke. There is no evidence to support the timing or choice of nutritional method which should be used in stroke patients. The present prospective study aimed to investigate the effect of early enteral nutrition on the short term outcomes of ⇑ Corresponding author. Tel.: +86 21 5666 3031. E-mail address: [email protected] (S. Wang).
acute stroke patients by supplying all the necessary nutrients and comparing to patients whose nutrition was family managed.
2. Methods 2.1. Subjects In this randomized controlled study, 146 acute stroke patients (including ischemic stroke and intracerebral hemorrhage) hospitalized during the period of July 2011 to December 2013 were included. Of these, 75 patients who were admitted to the comprehensive stroke unit were supported with nasogastric nutrition. Among them, 43 were men and the average age was 71.4 years ± standard deviation 9.3. The control group consisted of 71 patients who were admitted to the regular ward and received family managed nutrition. Among them, 42 were men and the average age was 71.8 years ± standard deviation 10.1. The distributions of stroke subtypes and baseline clinical characteristics in the two groups are presented in Table 1.
http://dx.doi.org/10.1016/j.jocn.2015.03.028 0967-5868/Ó 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Zheng T et al. Impact of early enteral nutrition on short term prognosis after acute stroke. J Clin Neurosci (2015), http:// dx.doi.org/10.1016/j.jocn.2015.03.028
2
T. Zheng et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx
2.3. Measurements
Table 1 Baseline information of acute stroke patients Treatment group
Control group
Patients, n Age, years (mean ± SD) Male sex, n (%)
75 71.4 ± 9.3 43 (57.3)
71 71.8 ± 10.1 42 (59.2)
Type of stroke Hemorrhagic, n (%) Ischemic, n (%) Mixed stroke, n (%)
22 (29.4) 49 (65.3) 4 (5.3)
24 (33.8) 45 (63.4) 2 (2.8)
Co-morbidities Disturbance of consciousness, n (%) Hypertension, n (%) Diabetes, n (%) Ischemic heart disease, n (%) Past stroke, n (%)
25 64 29 27 27
21 58 25 31 23
(33.3) (85.3) (37.3) (38.7) (36.0)
(29.6) (81.7) (35.2) (43.7) (32.4)
Two doctors, who were blinded to the treatment regimen, received training before the trial and started performing measurements after they reached a high inter-rater agreement. The measurements taken and time points were as follows: 1 Nutritional status and rate of malnutrition: calculated TSF, AMC, Hb, Alb, TG and the rate of malnutrition on the first, seventh, and twenty-first day of admission. 2 Nosocomial infection and mortality rates. 3 Neurological evaluation: National Institutes of Health Stroke Scale (NIHSS) [14], activities of daily living Barthel index (ADLBI) [15], and modified Rankin scale (mRS) [16] on the first and twenty-first day of admission.
SD = standard deviation.
2.4. Statistical analyses The selection criteria included: (1) cerebral infarction, intracranial hemorrhage or both confirmed with a CT scan or MRI within 72 hours of onset; (2) all patients who met the diagnostic standard of the Fourth National Cerebrovascular Events Conference (Chinese Neuroscience Society and Chinese Neurosurgery Society); (3) patients who might have a medical history of stroke but no apparent neurological deficit remaining prior to the onset of the current stroke; (4) focal neurological signs and dysphagia. Exclusion criteria included transient ischemic attack, subarachnoid hemorrhage, severe endocrine or metabolic disorders, hematological disorders, malignancies, chronic lung and heart dysfunction, severe liver or kidney failure, stress ulcer of the digestive system, and those who died within a week of admission. Patients who received thrombolytic therapy were not included in the present study. The two groups received similar pharmacological treatments. For hemorrhagic stroke patients, medications were used to reduce intracranial pressure (mannitol, furosemide), stabilize blood pressure and maintain optimal metabolism of neurons (monosialotetrahexosyl ganglioside). For ischemic stroke patients, antiplatelets, antithrombotic agents and statins were administered. Patients who were confirmed to have dysphagia were supported with nasogastric nutrition within 72 hours of admission and this lasted at least 10 days. Dysphagia refers to a difficulty in swallowing and Grade 3 or more in Kubota’s drinking test (Kubota et al., 1982) or unconsciousness. 2.2. Nutrition regimen The treatment group received either Nutrison fiber (Nutricia; Groupe Danone, Paris France), Swiss High (RAE; 4.18–6.27 kJ/ml), or a solution with high nutrition content made by nutritionists in our hospital and based on condition, body weight, and nutritional status. Energy requirements were in the range of 83.68–125.52 kJ/kg/day (1kcalth = 4.184 kJ). These solutions were infused by gravity under the supervision of nurses with a starting speed of 40–60 ml/hour. If there were no adverse events such as reflux, diarrhea or flatulence the speed was adjusted to 100–125 ml/hour. The total volume for the first day was 500 ml followed by an increase of 500 ml/day until the requirement was met. The control group received regular food from their families which consisted of milk, soymilk, juice, vegetable juice, broth, congee and eggs. Nutritional status was measured with physical measurements and laboratory tests. These included the thickness of the triceps skinfold of the unparalyzed side (TSF), arm muscle circumference (AMC), hemoglobin (Hb), albumin (Alb) and triglyceride (TG). If TSF or AMC of the patient was 10% lower than the standard of the normal population and Alb lower than 35 g/l, the patient was considered to be malnourished [13].
SAS (version 6.12; SAS Institute Inc., Cary, NC, USA) was used to analyze the differences in indices between the two groups. Continuous data were presented as the mean ± standard deviation and compared by t-test. Categorical data were compared by the chi-squared test. Statistically significant differences were indicated by p < 0.05. 3. Results 3.1. Characteristics of subjects In general, there were no significant differences in age, sex, type of stroke and past medical history between the two groups (Table 1). 3.2. Changes in nutritional status There were no significant differences in nutritional indices on the first day of admission (p > 0.05). These indices decreased on the seventh day of admission compared to the first day, and AMC of the control group was significantly smaller than that of the treatment group (t-test 2.240; p = 0.027). These indices continued to decrease after 21 days of admission but there was a trend of increase in Hb and Alb in the treatment group. TSF (t-test 2.124; p = 0.036), AMC (t-test 3.161; p = 0.002), Hb (t-test 2.428; p = 0.017), Alb (t-test 2.554; p = 0.012), and TG (t-test 2.262; p = 0.025) of the treatment group were statistically significantly higher than those of the control group (Table 2). 3.3. Rate of malnutrition The rate of malnutrition on the first day of admission was 17.3% in the treatment group (13/75) and 15.4% in the control group (11/71). There was no significant difference between the two groups (p > 0.05). This rate increased to 21.3% in the treatment group and 28.2% in the control group on the seventh day of admission. It continued to rise to 27.1% (19/70) in the treatment group and 48.3% (28/58) in the control group after 21 days (chi-squared 6.096; p = 0.014). 3.4. Nosocomial infection and mortality rates and the underlying causes of mortality In the treatment group, 25 patients (33.3%) had infections of the lungs, digestive tract, urinary tract and decubitus. In comparison, 37 patients (52.1%) from the control group had these infections. The infection rate in the treatment group was significantly lower
Please cite this article in press as: Zheng T et al. Impact of early enteral nutrition on short term prognosis after acute stroke. J Clin Neurosci (2015), http:// dx.doi.org/10.1016/j.jocn.2015.03.028
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T. Zheng et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx Table 2 Changes in nutritional indices in acute stroke patients at day 1, 7 and 21 of admission Group
n
TSF (mm)
AMC (cm)
Hb (g/L)
Alb (g/L)
TG (mmol/L)
Treatment Day 1 Day 7 Day 21
75 75 70
14.92 ± 3.23 14.05 ± 3.06 13.69 ± 2.33*
25.04 ± 2.17 21.88 ± 2.11* 21.32 ± 2.29**
135.6 ± 14.3 127.5 ± 12.8 129.6 ± 15.2*
39.6 ± 3.62 37.1 ± 3.24 37.8 ± 2.98*
1.33 ± 0.59 1.27 ± 0.47 1.18 ± 0.24*
Control Day 1 Day 7 Day 21
71 71 58
14.83 ± 3.42 13.62 ± 3.25 12.78 ± 2.51
24.95 ± 2.09 21.09 ± 2.15 20.11 ± 1.98
134.5 ± 15.1 125.3 ± 13.6* 123.2 ± 14.4
40.1 ± 3.45 37.5 ± 3.18 36.4 ± 3.21
1.36 ± 0.63 1.29 ± 0.55 1.07 ± 0.31
All values are reported as the mean ± standard deviation. * p < 0.05. ** p < 0.01. Alb = albumin, AMC = arm muscle circumference, Hb = hemoglobin, TG = triglyceride, TSF = triceps skinfold.
than that in the control group (chi-squared 5.265; p = 0.022; Table 3). After 21 days of admission, five patients (6.7%) from the treatment group and 13 (18.3%) from the control group had died (chi-squared 4.574; p = 0.032). The causes of death were hernia (n = 3), myocardial infarction (n = 1) and multiple organ failure due to a severe infection (n = 1) in the treatment group, and hernia (n = 6), lung infection (n = 4), multiple organ failure due to a severe infection (n = 1), refractory electrolyte disturbance with paralytic ileus (n = 1), and heart failure (n = 1) in the control group. 3.5. Neurological deficits The baseline NIHSS scores on the first day of admission for the treatment group and the control group were 12.53 ± 3.32 and 13.21 ± 3.78, respectively. The difference in this score was not statistically significant (p > 0.05). After 21 days, the NIHSS scores of the treatment group and the control group were 10.78 ± 2.69 and 12.04 ± 2.55, respectively. The NIHSS score was improved compared with that on the first day of admission in each group. Interestingly, the treatment group showed a better score than that of the control group after 21 days (t-test 2.701; p = 0.008). The baseline ADLBI scores of the treatment and control groups were 41.1 ± 11.6 and 42.3 ± 12.8, respectively. There was no significant difference between the two groups. After 21 days, these scores were 46.7 ± 8.8 and 44.4 ± 9.3, respectively. The difference between the two groups was statistically insignificant (t-test 1.435; p = 0.154). After 90 days, four treatment group patients and two control patients were lost from follow-up. Therefore, the total numbers of patients with available mRS on day 90 were 66 and 56 for the treatment and control group, respectively. For 90 day mRS, 14 (21.2%) and 9 (16.1%) patients from the treatment and control groups scored 0–1, 25 (37.9%) and 16 (28.6%) scored 2– 3, and 27 (40.9%) and 31 (55.3%) scored 4–5, respectively. There was no significant difference in mRS scores between the two groups after 90 days. 4. Discussion Prevention and treatment of stroke in China closely follow the guidelines that have been developed in western countries. The most prevalent model still focuses on medication and the passive
Table 3 Infections in the treatment and control groups
*
Patient group
n
Treatment Control
75 71
p < 0.05.
Infection type, n Lung
Enteral
Urinary
Decubitus
Total
11 15
6 9
8 10
0 3
25 37
Infection rate (%) 33.3* 52.1
acceptance of medical treatment by the patient [17]. Throughout the management of stroke patients, clinicians often lack knowledge regarding nutritional support, leading to neglect of the patient’s nutritional status. The American Stroke Association and Heart Association guidelines for the early management of patients with acute ischemic stroke [18] recommend that all stroke patients should be evaluated for their baseline nutritional status and any malnutrition should be corrected or improved as soon as possible. The present study shows that strict nutritional support improves the short term nutritional status and neurological performance of acute stroke patients with dysphagia. These patients, treated with nasogastric nutrition in the stroke unit within 72 hours of admission, have better results in nutrition tests at 21 days than those who receive family managed nutrition. The malnutrition rates were 27.2% and 48.3% in the treatment and control groups, respectively. The direct cause of the poor nutritional status among the family managed nutrition patients might be insufficient nutrients provided from the meals and poor monitoring mechanisms. Complications such as nosocomial infections are closely related to the immune status of patients, and this is compromised when they are malnourished [19]. This fact might be a main cause of increased infection rates and deterioration which lead to a poor short term prognosis in these patients. The feed or ordinary diet (FOOD) trial conducted in 2003 shows that early nasogastric nutrition within a week of admission reduces the mortality rate and risk of poor outcomes [20]. In the present study, the mortality and infection rates were significantly different between the two groups (chi-squared 4.574; p = 0.032; chi-squared 5.265; p = 0.022). This suggests that the mortality rate is correlated with the infection rate. Among the patients who died in the control group, 53.8% of had infections. Therefore, it appears that prevention and treatment of malnutrition are essential in reducing the infection and mortality rates in patients with acute stroke. The present study shows that early nasogastric nutrition improves neurological performance, as demonstrated by the decrease in NIHSS score after 21 days (p = 0.008). This indicates that early nasogastric nutrition helps the recovery of neurological functions. This is consistent with the results of an earlier study [21]. However, the difference in ADLBI scores between the two groups was not significant which suggests a poor correlation between ADLBI score and the recovery of neurological performance. In order to accelerate the recovery of their daily activities, patients need other treatments in addition to nutritional support such as early rehabilitation. This deserves the attention of clinicians. The mRS scores on day 90 were not significantly different between the two groups and the majority of patients were moderately or severely disabled. This suggests that patients can benefit from early nutrition support in the short term to aid recovery of neurological functions, but those who have remaining disabilities post stroke need a long term nutrition management plan.
Please cite this article in press as: Zheng T et al. Impact of early enteral nutrition on short term prognosis after acute stroke. J Clin Neurosci (2015), http:// dx.doi.org/10.1016/j.jocn.2015.03.028
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T. Zheng et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx
Implementation of the right nutrition management plan for stroke patients should be an important part of the standard practice in stroke treatment. The present study demonstrates a decline of nutritional indices and an increase of malnutrition rates, especially in severely ill patients and even after early nasogastric nutrition support. This indicates that the intake of nutrients from the early nasogastric infusion did not meet the metabolic requirements of the patients. This is consistent with findings from a previous study [22] which showed that early nutritional support did not stop the deterioration of nutritional status of acute stroke patients after a week. The reason for this might lie in the disturbance of hypothalamic and brainstem function. This leads to disrupted excretion of gastrointestinal hormones and enzymes and damage to the mucosal membrane barrier of the intestines. As a result, absorption of nutrients is decreased and malnutrition occurs. More research is required to investigate whether the combination of enteral and parenteral nutrition or short peptide nutrition and subsequent whole protein nutrition should be implemented in stroke patients in order to improve their prognoses. 5. Conclusion Early nasogastric nutrition improves short term nutritional status and reduces complications in patients with acute stroke and dysphagia. Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. Acknowledgments We thank the Shanghai Bureau of Health for its support in the establishment and implementation of the stroke management model in Shanghai. References [1] Corrigan ML, Escuro AA, Celestin J, et al. Nutrition in the stroke patient. Nutr Clin Pract 2011;26:242–52. [2] Hutchinson E, Wilson N. Acute stroke, dysphagia and nutritional support. Br J Community Nurs 2013:S26–9.
[3] National Alliance for Infusion Therapy and the American Society for Parenteral and Enteral Nutrition Public Policy Committee and Board of Directors. Diseaserelated malnutrition and enteral nutrition therapy: a significant problem with a cost-effective solution. Nutr Clin Pract 2010;25:548–54. [4] VITATOPS Trial Study Group. B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial. Lancet Neurol 2010;9:855–65. [5] Marti-Carvajal AJ, Sola I, Lathyris D, et al. Homocysteine lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev 2009;4:CD006612. [6] Alkhenizan AH, Al-Omran MA. The role of vitamin E in the prevention of coronary events and stroke – meta-analysis of randomized controlled trials. Saudi Med J 2004;25:1808–14. [7] Bin Q, Hu X, Cao Y, et al. The role of vitamin E (tocopherol) supplementation in the prevention of stroke A meta-analysis of 13 randomised controlled trials. Thromb Haemost 2011;105:579–85. [8] Eidelman RS, Hollar D, Hebert PR, et al. Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease. Arch Intern Med 2004;164:1552–6. [9] Hooper L, Summerbell CD, Higgins JP, et al. Reduced or modified dietary fat for preventing cardiovascular disease. Cochrane Database Syst Rev 2001;3:CD002137. [10] Marik PE, Varon J. Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review. Clin Cardiol 2009;32:365–72. [11] Tanaka K, Ishikawa Y, Yokoyama M, et al. Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients – subanalysis of the JELIS trial. Stroke 2008;39:2052–8. [12] Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 1999;354:447–55. [13] Wu GH. Practical clinical nutrition. Shanghai: Fudan University Press; 2006. [14] Brott T, Adams Jr HP, Olinger CP, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke 1989;20:864–70. [15] Wade DT, Collin C. The Barthel ADL Index: a standard measure of physical disability? Int Disabil Stud 1988;10:64–7. [16] Bonita R, Beaglehole R. Recovery of motor function after stroke. Stroke 1988;19:1497–500. [17] Wang YJ, Zhao XQ, Wang SS, et al. Expert consensus statement on the management of dysphagia and nutrition after stroke. Chin J Stroke 2013;8:973–83. [18] Jauch EC, Saver JL, Adams Jr HP, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:870–947. [19] Chandra RK. Nutrition and the immune system: an introduction. Am J Clin Nutr 1997;66:460S–3S. [20] Dennis MS, Lewis SC, Warlow C. Effect of timing and method of enteral tube feeding for dysphagic stroke patients: a multicentre randomized controlled trial. Lancet 2005;365:764–72. [21] Perel P, Yanagawa T, Bunn F, et al. Nutritional support for head-injured patients. Cochrane Database Syst Rev 2006;4:CD001530. [22] Dávalos A, Ricart W, Gonzalez-Huix F, et al. Effect of malnutrition after acute stroke on clinical outcome. Stroke 1996;27:1028–32.
Please cite this article in press as: Zheng T et al. Impact of early enteral nutrition on short term prognosis after acute stroke. J Clin Neurosci (2015), http:// dx.doi.org/10.1016/j.jocn.2015.03.028
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Impact of early enteral nutrition on short term prognosis after acute stroke Tianheng Zheng a, Xinpu Zhu a, Huazheng Liang a,b, Haixia Huang a, Jiandao Yang a, Shaoshi Wang a,⇑ a b
Department of Neurology, Branch of the People’s First Hospital, 1878 North Sichuan Road, Hongkou District, Shanghai 200081, China Neuroscience Research Australia, Randwick, NSW, Australia
a r t i c l e
i n f o
Article history: Received 8 December 2014 Accepted 3 March 2015 Available online xxxx Keywords: Dysphagia Nutrition support Post stroke infection Short term prognosis Stroke
a b s t r a c t We hypothesized that early enteral nutritional support would improve the short term prognosis of acute stroke patients with dysphagia, demonstrated by lower malnutrition rates, lower complication rates, and lower National Institutes of Health Stroke Scale (NIHSS) scores at 90 days post stroke. Nutrition support is an essential element in the care of stroke patients and many studies have investigated the effect of specific nutritional elements on stroke patients. However, few studies have looked at the impact of complete enteral nutrition on Chinese patients with acute stroke. To investigate this, we conducted a randomized controlled trial of 146 patients with acute stroke and dysphagia, among whom 75 were supported with nasogastric nutrition and 71 received family managed nutrition after randomization. Nutritional status, nosocomial infection and mortality rates were recorded on day 21 of hospitalization. Neurological deficits were evaluated by the NIHSS activities of daily living Barthel index (ADLBI) and the modified Rankin scale (mRS) and compared between the two groups. We found that the nasogastric nutrition group had a better nutritional status and reduced nosocomial infection and mortality rates after 21 days compared with patients in the family managed nutrition group. In addition, the nasogastric nutrition group showed a lower score on the NIHSS than the control group. However, the differences in the scores of the ADLBI and the 90 day mRS between the groups were not significant. Taken together, the present study shows that early enteral nutrition support improves the short term prognosis of acute stroke patients with dysphagia. Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction Malnutrition is a potential complication during the rehabilitation of stroke patients. Its incidence varies from 6.1 to 62.0% among stroke patients due to the differences in methodologies and the time of evaluation of nutritional status [1]. It also increases the incidence of post stroke infection, recurrent stroke and mortality, resulting in a poor prognosis ([2]). It has been shown that the nutritional status of stroke patients is closely related to their long term clinical outcome [3]. Though a large number of studies have investigated the effect of specific nutrients on the recurrence of stroke such as vitamin B, folic acid ([4,5], antioxidants [6–8], and fat [9–12]), none have shown significant improvements in mortality and recurrence of stroke. There is no evidence to support the timing or choice of nutritional method which should be used in stroke patients. The present prospective study aimed to investigate the effect of early enteral nutrition on the short term outcomes of ⇑ Corresponding author. Tel.: +86 21 5666 3031. E-mail address: [email protected] (S. Wang).
acute stroke patients by supplying all the necessary nutrients and comparing to patients whose nutrition was family managed.
2. Methods 2.1. Subjects In this randomized controlled study, 146 acute stroke patients (including ischemic stroke and intracerebral hemorrhage) hospitalized during the period of July 2011 to December 2013 were included. Of these, 75 patients who were admitted to the comprehensive stroke unit were supported with nasogastric nutrition. Among them, 43 were men and the average age was 71.4 years ± standard deviation 9.3. The control group consisted of 71 patients who were admitted to the regular ward and received family managed nutrition. Among them, 42 were men and the average age was 71.8 years ± standard deviation 10.1. The distributions of stroke subtypes and baseline clinical characteristics in the two groups are presented in Table 1.
http://dx.doi.org/10.1016/j.jocn.2015.03.028 0967-5868/Ó 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Zheng T et al. Impact of early enteral nutrition on short term prognosis after acute stroke. J Clin Neurosci (2015), http:// dx.doi.org/10.1016/j.jocn.2015.03.028
2
T. Zheng et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx
2.3. Measurements
Table 1 Baseline information of acute stroke patients Treatment group
Control group
Patients, n Age, years (mean ± SD) Male sex, n (%)
75 71.4 ± 9.3 43 (57.3)
71 71.8 ± 10.1 42 (59.2)
Type of stroke Hemorrhagic, n (%) Ischemic, n (%) Mixed stroke, n (%)
22 (29.4) 49 (65.3) 4 (5.3)
24 (33.8) 45 (63.4) 2 (2.8)
Co-morbidities Disturbance of consciousness, n (%) Hypertension, n (%) Diabetes, n (%) Ischemic heart disease, n (%) Past stroke, n (%)
25 64 29 27 27
21 58 25 31 23
(33.3) (85.3) (37.3) (38.7) (36.0)
(29.6) (81.7) (35.2) (43.7) (32.4)
Two doctors, who were blinded to the treatment regimen, received training before the trial and started performing measurements after they reached a high inter-rater agreement. The measurements taken and time points were as follows: 1 Nutritional status and rate of malnutrition: calculated TSF, AMC, Hb, Alb, TG and the rate of malnutrition on the first, seventh, and twenty-first day of admission. 2 Nosocomial infection and mortality rates. 3 Neurological evaluation: National Institutes of Health Stroke Scale (NIHSS) [14], activities of daily living Barthel index (ADLBI) [15], and modified Rankin scale (mRS) [16] on the first and twenty-first day of admission.
SD = standard deviation.
2.4. Statistical analyses The selection criteria included: (1) cerebral infarction, intracranial hemorrhage or both confirmed with a CT scan or MRI within 72 hours of onset; (2) all patients who met the diagnostic standard of the Fourth National Cerebrovascular Events Conference (Chinese Neuroscience Society and Chinese Neurosurgery Society); (3) patients who might have a medical history of stroke but no apparent neurological deficit remaining prior to the onset of the current stroke; (4) focal neurological signs and dysphagia. Exclusion criteria included transient ischemic attack, subarachnoid hemorrhage, severe endocrine or metabolic disorders, hematological disorders, malignancies, chronic lung and heart dysfunction, severe liver or kidney failure, stress ulcer of the digestive system, and those who died within a week of admission. Patients who received thrombolytic therapy were not included in the present study. The two groups received similar pharmacological treatments. For hemorrhagic stroke patients, medications were used to reduce intracranial pressure (mannitol, furosemide), stabilize blood pressure and maintain optimal metabolism of neurons (monosialotetrahexosyl ganglioside). For ischemic stroke patients, antiplatelets, antithrombotic agents and statins were administered. Patients who were confirmed to have dysphagia were supported with nasogastric nutrition within 72 hours of admission and this lasted at least 10 days. Dysphagia refers to a difficulty in swallowing and Grade 3 or more in Kubota’s drinking test (Kubota et al., 1982) or unconsciousness. 2.2. Nutrition regimen The treatment group received either Nutrison fiber (Nutricia; Groupe Danone, Paris France), Swiss High (RAE; 4.18–6.27 kJ/ml), or a solution with high nutrition content made by nutritionists in our hospital and based on condition, body weight, and nutritional status. Energy requirements were in the range of 83.68–125.52 kJ/kg/day (1kcalth = 4.184 kJ). These solutions were infused by gravity under the supervision of nurses with a starting speed of 40–60 ml/hour. If there were no adverse events such as reflux, diarrhea or flatulence the speed was adjusted to 100–125 ml/hour. The total volume for the first day was 500 ml followed by an increase of 500 ml/day until the requirement was met. The control group received regular food from their families which consisted of milk, soymilk, juice, vegetable juice, broth, congee and eggs. Nutritional status was measured with physical measurements and laboratory tests. These included the thickness of the triceps skinfold of the unparalyzed side (TSF), arm muscle circumference (AMC), hemoglobin (Hb), albumin (Alb) and triglyceride (TG). If TSF or AMC of the patient was 10% lower than the standard of the normal population and Alb lower than 35 g/l, the patient was considered to be malnourished [13].
SAS (version 6.12; SAS Institute Inc., Cary, NC, USA) was used to analyze the differences in indices between the two groups. Continuous data were presented as the mean ± standard deviation and compared by t-test. Categorical data were compared by the chi-squared test. Statistically significant differences were indicated by p < 0.05. 3. Results 3.1. Characteristics of subjects In general, there were no significant differences in age, sex, type of stroke and past medical history between the two groups (Table 1). 3.2. Changes in nutritional status There were no significant differences in nutritional indices on the first day of admission (p > 0.05). These indices decreased on the seventh day of admission compared to the first day, and AMC of the control group was significantly smaller than that of the treatment group (t-test 2.240; p = 0.027). These indices continued to decrease after 21 days of admission but there was a trend of increase in Hb and Alb in the treatment group. TSF (t-test 2.124; p = 0.036), AMC (t-test 3.161; p = 0.002), Hb (t-test 2.428; p = 0.017), Alb (t-test 2.554; p = 0.012), and TG (t-test 2.262; p = 0.025) of the treatment group were statistically significantly higher than those of the control group (Table 2). 3.3. Rate of malnutrition The rate of malnutrition on the first day of admission was 17.3% in the treatment group (13/75) and 15.4% in the control group (11/71). There was no significant difference between the two groups (p > 0.05). This rate increased to 21.3% in the treatment group and 28.2% in the control group on the seventh day of admission. It continued to rise to 27.1% (19/70) in the treatment group and 48.3% (28/58) in the control group after 21 days (chi-squared 6.096; p = 0.014). 3.4. Nosocomial infection and mortality rates and the underlying causes of mortality In the treatment group, 25 patients (33.3%) had infections of the lungs, digestive tract, urinary tract and decubitus. In comparison, 37 patients (52.1%) from the control group had these infections. The infection rate in the treatment group was significantly lower
Please cite this article in press as: Zheng T et al. Impact of early enteral nutrition on short term prognosis after acute stroke. J Clin Neurosci (2015), http:// dx.doi.org/10.1016/j.jocn.2015.03.028
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T. Zheng et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx Table 2 Changes in nutritional indices in acute stroke patients at day 1, 7 and 21 of admission Group
n
TSF (mm)
AMC (cm)
Hb (g/L)
Alb (g/L)
TG (mmol/L)
Treatment Day 1 Day 7 Day 21
75 75 70
14.92 ± 3.23 14.05 ± 3.06 13.69 ± 2.33*
25.04 ± 2.17 21.88 ± 2.11* 21.32 ± 2.29**
135.6 ± 14.3 127.5 ± 12.8 129.6 ± 15.2*
39.6 ± 3.62 37.1 ± 3.24 37.8 ± 2.98*
1.33 ± 0.59 1.27 ± 0.47 1.18 ± 0.24*
Control Day 1 Day 7 Day 21
71 71 58
14.83 ± 3.42 13.62 ± 3.25 12.78 ± 2.51
24.95 ± 2.09 21.09 ± 2.15 20.11 ± 1.98
134.5 ± 15.1 125.3 ± 13.6* 123.2 ± 14.4
40.1 ± 3.45 37.5 ± 3.18 36.4 ± 3.21
1.36 ± 0.63 1.29 ± 0.55 1.07 ± 0.31
All values are reported as the mean ± standard deviation. * p < 0.05. ** p < 0.01. Alb = albumin, AMC = arm muscle circumference, Hb = hemoglobin, TG = triglyceride, TSF = triceps skinfold.
than that in the control group (chi-squared 5.265; p = 0.022; Table 3). After 21 days of admission, five patients (6.7%) from the treatment group and 13 (18.3%) from the control group had died (chi-squared 4.574; p = 0.032). The causes of death were hernia (n = 3), myocardial infarction (n = 1) and multiple organ failure due to a severe infection (n = 1) in the treatment group, and hernia (n = 6), lung infection (n = 4), multiple organ failure due to a severe infection (n = 1), refractory electrolyte disturbance with paralytic ileus (n = 1), and heart failure (n = 1) in the control group. 3.5. Neurological deficits The baseline NIHSS scores on the first day of admission for the treatment group and the control group were 12.53 ± 3.32 and 13.21 ± 3.78, respectively. The difference in this score was not statistically significant (p > 0.05). After 21 days, the NIHSS scores of the treatment group and the control group were 10.78 ± 2.69 and 12.04 ± 2.55, respectively. The NIHSS score was improved compared with that on the first day of admission in each group. Interestingly, the treatment group showed a better score than that of the control group after 21 days (t-test 2.701; p = 0.008). The baseline ADLBI scores of the treatment and control groups were 41.1 ± 11.6 and 42.3 ± 12.8, respectively. There was no significant difference between the two groups. After 21 days, these scores were 46.7 ± 8.8 and 44.4 ± 9.3, respectively. The difference between the two groups was statistically insignificant (t-test 1.435; p = 0.154). After 90 days, four treatment group patients and two control patients were lost from follow-up. Therefore, the total numbers of patients with available mRS on day 90 were 66 and 56 for the treatment and control group, respectively. For 90 day mRS, 14 (21.2%) and 9 (16.1%) patients from the treatment and control groups scored 0–1, 25 (37.9%) and 16 (28.6%) scored 2– 3, and 27 (40.9%) and 31 (55.3%) scored 4–5, respectively. There was no significant difference in mRS scores between the two groups after 90 days. 4. Discussion Prevention and treatment of stroke in China closely follow the guidelines that have been developed in western countries. The most prevalent model still focuses on medication and the passive
Table 3 Infections in the treatment and control groups
*
Patient group
n
Treatment Control
75 71
p < 0.05.
Infection type, n Lung
Enteral
Urinary
Decubitus
Total
11 15
6 9
8 10
0 3
25 37
Infection rate (%) 33.3* 52.1
acceptance of medical treatment by the patient [17]. Throughout the management of stroke patients, clinicians often lack knowledge regarding nutritional support, leading to neglect of the patient’s nutritional status. The American Stroke Association and Heart Association guidelines for the early management of patients with acute ischemic stroke [18] recommend that all stroke patients should be evaluated for their baseline nutritional status and any malnutrition should be corrected or improved as soon as possible. The present study shows that strict nutritional support improves the short term nutritional status and neurological performance of acute stroke patients with dysphagia. These patients, treated with nasogastric nutrition in the stroke unit within 72 hours of admission, have better results in nutrition tests at 21 days than those who receive family managed nutrition. The malnutrition rates were 27.2% and 48.3% in the treatment and control groups, respectively. The direct cause of the poor nutritional status among the family managed nutrition patients might be insufficient nutrients provided from the meals and poor monitoring mechanisms. Complications such as nosocomial infections are closely related to the immune status of patients, and this is compromised when they are malnourished [19]. This fact might be a main cause of increased infection rates and deterioration which lead to a poor short term prognosis in these patients. The feed or ordinary diet (FOOD) trial conducted in 2003 shows that early nasogastric nutrition within a week of admission reduces the mortality rate and risk of poor outcomes [20]. In the present study, the mortality and infection rates were significantly different between the two groups (chi-squared 4.574; p = 0.032; chi-squared 5.265; p = 0.022). This suggests that the mortality rate is correlated with the infection rate. Among the patients who died in the control group, 53.8% of had infections. Therefore, it appears that prevention and treatment of malnutrition are essential in reducing the infection and mortality rates in patients with acute stroke. The present study shows that early nasogastric nutrition improves neurological performance, as demonstrated by the decrease in NIHSS score after 21 days (p = 0.008). This indicates that early nasogastric nutrition helps the recovery of neurological functions. This is consistent with the results of an earlier study [21]. However, the difference in ADLBI scores between the two groups was not significant which suggests a poor correlation between ADLBI score and the recovery of neurological performance. In order to accelerate the recovery of their daily activities, patients need other treatments in addition to nutritional support such as early rehabilitation. This deserves the attention of clinicians. The mRS scores on day 90 were not significantly different between the two groups and the majority of patients were moderately or severely disabled. This suggests that patients can benefit from early nutrition support in the short term to aid recovery of neurological functions, but those who have remaining disabilities post stroke need a long term nutrition management plan.
Please cite this article in press as: Zheng T et al. Impact of early enteral nutrition on short term prognosis after acute stroke. J Clin Neurosci (2015), http:// dx.doi.org/10.1016/j.jocn.2015.03.028
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T. Zheng et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx
Implementation of the right nutrition management plan for stroke patients should be an important part of the standard practice in stroke treatment. The present study demonstrates a decline of nutritional indices and an increase of malnutrition rates, especially in severely ill patients and even after early nasogastric nutrition support. This indicates that the intake of nutrients from the early nasogastric infusion did not meet the metabolic requirements of the patients. This is consistent with findings from a previous study [22] which showed that early nutritional support did not stop the deterioration of nutritional status of acute stroke patients after a week. The reason for this might lie in the disturbance of hypothalamic and brainstem function. This leads to disrupted excretion of gastrointestinal hormones and enzymes and damage to the mucosal membrane barrier of the intestines. As a result, absorption of nutrients is decreased and malnutrition occurs. More research is required to investigate whether the combination of enteral and parenteral nutrition or short peptide nutrition and subsequent whole protein nutrition should be implemented in stroke patients in order to improve their prognoses. 5. Conclusion Early nasogastric nutrition improves short term nutritional status and reduces complications in patients with acute stroke and dysphagia. Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. Acknowledgments We thank the Shanghai Bureau of Health for its support in the establishment and implementation of the stroke management model in Shanghai. References [1] Corrigan ML, Escuro AA, Celestin J, et al. Nutrition in the stroke patient. Nutr Clin Pract 2011;26:242–52. [2] Hutchinson E, Wilson N. Acute stroke, dysphagia and nutritional support. Br J Community Nurs 2013:S26–9.
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