The Incidence of Dysphagia in Patients Receiving Cerebral Reperfusion Therapy Poststroke Priscila W. Ribeiro, MSc,* Paula C. Cola, MD,† Ana R. Gatto, MSc,† Roberta G. da Silva, PhD,† Gustavo J. Luvizutto, MSc,* Gabriel P. Braga, MSc,* Arthur O. Schelp, MD,* Maria A. C. de Arruda Henry, MD,‡ and Rodrigo Bazan, MD*
Background: The high prevalence of dysphagia after stroke leads to increased mortality, and cerebral reperfusion therapy has been effective in reducing neurologic deficits. The aim of this study was to investigate the severity and evolution of dysphagia and the occurrence of pneumonia in patients submitted to cerebral reperfusion therapy. Methods: Seventy ischemic stroke patients were evaluated. Of these, 35 patients (group 1) were submitted to cerebral reperfusion therapy and 35 (group 2) did not receive thrombolytic treatment. The following were evaluated: severity of dysphagia by means of videofluoroscopy, evolution of oral intake rate by means of the Functional Oral Intake Scale, and the occurrence of pneumonia by international protocol. The relation between the severity of dysphagia and the occurrence of pneumonia with the treatment was evaluated through the chi-square test; the daily oral intake rate and its relation to the treatment were assessed by the Mann–Whitney test and considered significant if P is less than .05. Results: The moderate and severe degrees of dysphagia were more frequent (P 5 .013) among the patients who were not submitted to cerebral reperfusion therapy. The daily oral intake evolved independently of the treatment type, without statistical significance when compared between the groups, whereas pneumonia occurred more frequently in group 2 (28%) in relation to group 1 (11%) and was associated with the worst degrees of dysphagia (P 5.045). Conclusions: We can conclude that there is improvement in the oral intake rate in both groups, with lower severity of dysphagia and occurrence of pneumonia in ischemic stroke patients submitted to cerebral reperfusion therapy. Key Words: Stroke—thrombolytic therapy—deglutition—deglutition disorders—dysphagia. Ó 2014 by National Stroke Association
Introduction From the *Neurology Service, Botucatu School of Medicine, University Estadual Paulista J ulio de Mesquita Filho, S~ao Paulo; †Department of Phonoaudiology, School of Pholosophy and Sciences, Marılia; and ‡Department of Surgery, Botucatu School of Medicine, University Estadual Paulista J ulio de Mesquita Filho, S~ ao Paulo, Brazil. Received November 13, 2013; accepted December 19, 2013. Grant support: None. Address correspondence to Gustavo J. Luvizutto, MSc, Botucatu School of Medicine, University Estadual Paulista J ulio de Mesquita Filho, District of Rubi~ao Junior, Botucatu, SP 18618-970, Brazil. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2014 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.12.033
Each year around 610,000 individuals have a stroke, which is one of the 3 main causes of death in countries around the world.1 In Brazil, it is the main cause of death in the adult population and responsible for 10% of all hospital admissions.2-4 As well as a high mortality index, ischemic stroke can cause communication and swallowing disorders, with a significant impact on an individual’s functional evolution.5 The incidence of oropharyngeal dysphagia is high, ranging between 51% and 91% in acute and subacute stroke phases.6-8 Dysphagia when associated with aspiration pneumonia can prolong hospital stay and increase mortality risk 3-fold.9,10 Early identification and
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treatment of dysphagia can reduce the risks of pulmonary, nutritional, and hydration complications and reduce hospital stay. It is, therefore, vital that effective treatment is given early to help reduce expected stroke sequelae. The swallowing evaluation aims to identify the presence of dysphagia and proposes the most secure alimentation route in the acute stroke phase.11 The advent of new treatment approaches in acute stroke phase has brought about prognostic and functional advances for the individual, including cerebral reperfusion therapy, a procedure described as capable of restoring blood flow by intravenous recombinant tissue plasminogen activator (rt-PA) infusion. Recent studies have shown that, when performed in the first 4.5 hours after symptom appearance, cerebral reperfusion therapy produces a significant reduction of functional incapacity, as measured by the modified Rankin Scale (mRS) and improvement of neurologic capacity, by the National Institutes of Health Stroke Scale (NIHSS) score in the first 24 hours. Furthermore, 31%-50% of rt-PA–treated cases show neurologic recuperation after 3 months.12,13 Even though oropharyngeal dysphagia is described as one of the high mortality sequelae in patients after stroke, there is no evidence in the literature of a therapeutic effect of cerebral reperfusion on swallowing. The present study aimed to investigate the severity and evolution of dysphagia and the incidence of pneumonia in patients submitted to cerebral reperfusion therapy. The central hypothesis of this study was to demonstrate that cerebral reperfusion therapy diminishes the severity of dysphagia, improves the oral intake rate, and reduces the pneumonia incidence after ischemic stroke.
Methods This was a prospective cohort study in ischemic stroke patients of both sexes, confirmed by cranial computerized tomography during hospitalization, under conservative or thrombolytic treatment in the stroke unit at the Botucatu School of Medicine University Hospital—UNESP (Univ Estadual Paulista), SP, Brazil. Patients were excluded if they presented hemorrhagic or posterior circulation stroke, previous mRS score greater than 1, preexisting dementia, unstable clinical, another neurologic disease, or had undergone decompressive hemicraniectomy. The study was approved by the Human Research Ethics Committee under directive 3496/2010, and all individuals gave their consent to participate in the study.
Procedures Patients were divided into 2 groups according to the neurologic treatment received during acute stroke phase. Group 1 was constituted by patients submitted to cerebral reperfusion therapy with intravenous rt-PA (.9 mg/kg), and group 2 by patients who did not receive cerebral re-
perfusion therapy on account of presenting at least one of the following exclusion criteria for thrombolysis: another stroke or serious head trauma within the preceding 3 months, major surgery within 14 days, history of intracranial hemorrhage, systolic blood pressure greater than 185 mm Hg, or diastolic blood pressure greater than 110 mm Hg; rapidly improving or minor symptoms; symptoms suggestive of subarachnoid hemorrhage; gastrointestinal hemorrhage or urinary tract hemorrhage within the previous 21 days; arterial puncture at a no compressible site within the previous 7 days; or seizure at the onset of stroke. All patients were monitored for clinical parameters (blood glucose, temperature, and arterial pressure) at the stroke unit.
Evaluation of Dysphagia Dysphagia was evaluated by means of videofluoroscopic recordings, using foods modified with barium sulfate. The exam was initiated by offering a pasty food, followed by a liquid. It is important to emphasize that the evolution of the offering’s quantity and consistency was directly dependent on the performance of the patient in the previous deglutition, with the exam being interrupted when the presence of laryngotracheal aspiration was observed. For the exam, the patient was advised to remain in a lateral position, which allows visualization of the upper and lower anatomical limits, from the oral cavity to the esophagus. From the exam analysis, the severity of dysphagia classifies dysphagia in 3 levels, defined as follows14: degree 1, mild (oral alterations without laryngeal penetration and/or laryngotracheal aspiration); degree 2, moderate (oral alterations, pharyngeal residues, and little penetration or laryngotracheal aspiration of a determinate consistency); and degree 3, severe (substantial laryngotracheal aspiration or failure to swallow). The patients with an absence of dysphagia were classified as degree 0.
Evolution of Daily Oral Intake Rate All patients were evaluated by the Functional Oral Intake Scale (FOIS), which classifies the quantity of oral intake into 7 specific levels: 1, nothing by mouth; 2, other route dependent on minimal oral attempts to ingest food or liquid; 3, other route dependent on some oral intake of food or liquid; 4, total oral diet of a single consistency; 5, total oral diet with multiple consistencies but requiring special preparation or compensations; 6, total oral diet with multiple consistencies without special preparation but with specific food limitations; and 7, total oral diet with no restrictions. Level 0 was established for patients who were fasting at initial evaluation.15 FOIS was initially applied by a speech therapist before and after videofluoroscopy and at discharge from the hospital. Patients were monitored during hospital stay with diet being modified when indicated and by interim re-
CEREBRAL REPERFUSION THERAPY AND DYSPHAGIA
evaluations, according to neurologic evolution. The rate of daily evolution was based on the relation between FOIS after videofluoroscopy (FOIS1) and hospital discharge (FOIS2), as a function of the time of hospitalization (th), according to the following calculation: (FOIS1 2 FOIS2/th).
Pneumonia The data on pneumonia were obtained by clinical, radiological, and laboratory evaluation during hospitalization, according to international protocol.16,17
Statistical Analysis To evaluate the relation between the dysphagia severity and the treatment received, the potential confounders were analyzed by logistic regression, whereas the relation between group 1 and group 2 was assessed by chi-square test. To evaluate the daily rate of oral intake and its relation to treatment, the Mann–Whitney test was used, whereas the incidence of pneumonia and its relation to the dysphagia degree were analyzed by chi square and considered significant if P is less than .05. Based on the dysphagia frequencies observed in both groups, it can be estimated that the power of the test is about 70%, supposing, for the effect of calculation, simple random sampling, type I error probability 5 .05, and the absence of confounding effects.
Results Between April 2011 and December 2012, 70 individuals neurologically diagnosed with ischemic stroke were divided into 2 groups of 35 patients each. The clinical and demographic data are presented in Table 1. Table 2 shows the absence of a significant relation between clinical and demographic data versus the dysphagia degree, so that the relation between treatment and dysphagia degree was analyzed without the necessity of considering any of the earlier mentioned variables, demonstrating the homogeneity between the groups. Table 3 shows a significant relation between treatment and dysphagia degree, with degrees 2 (moderate) and 3 (severe) being significantly more frequent (P 5 .013) among the patients
3
Table 1. Demographic data for thrombolysed and nonthrombolysed patient groups G1 (n 5 35)
G2 (n 5 35)
66.5 17 72.4 1.69 23.5 18 17 0 12.4 (4-22) 5.4 (1-17) 4.9
68.3 19 71.3 1.71 26.2 17 18 0 11.6 (1-24) 8 (1-17) 3.7
10.1
13.6
Variables* Age (y) Sex, male Weight (kg) Height (m) BMI (kg/m2) Right hemisphere Left hemisphere Previous mRS NIHSS at admission NIHSS at evaluation Ictus (admission to evaluation) (d) Time in hospital (d)
Abbreviations: BMI, body mass index; G1, patients submitted to cerebral reperfusion; G2, patients who did not receive cerebral reperfusion therapy; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale. *Numbers are mean (SD) or counts (%).
who were not submitted to cerebral reperfusion therapy (group 2). There was evolution of the daily oral intake rate independently of the treatment type, but it did not differ statistically between the groups (Table 4). The pneumonia rate among the studied patients during hospitalization was 20%. Table 5 shows that, despite not being statistically significant, the occurrence of pneumonia was more frequent in group 2 patients than group 1 (28% versus 11%). Table 6 shows that pneumonia was more frequent among the patients with the worst degrees of dysphagia being that, among those patients submitted to reperfusion, the relation between dysphagia degree and pneumonia was significant (P 5 .045).
Discussion Cerebral reperfusion therapy has been shown to improve immediate and long-term patient recovery after
Table 2. Relation between clinical and demographic data Variable
b
SE
Wald
P
OR (95% CI)
Age (y) Topography of lesion NIHSS at admission FOIS at admission Constant
.01 .90 .03 2.23 2.07
.02 .62 .06 .16 1.72
.39 2.06 .19 2.20 .00
.531 .152 .664 .138 .967
1.01 (.97-1.06) 2.45 (.72-8.33) 1.03 (.91-1.16) .79 (.58-1.08) .93
Abbreviations: CI, confidence interval; FOIS, Functional Oral Intake Scale; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; Wald, Wald test. b indicates estimated coefficient.
P.W. RIBEIRO ET AL.
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Table 3. Relation between treatment and degrees of dysphagia Degrees of dysphagia G1 (n 5 35) G2 (n 5 35) 0-1 2-3
18 (51%) 17 (49%)
8 (23%) 27 (77%)
Table 5. Comparison between treatments in relation to the percentage of patients with pneumonia
P .013
Pneumonia (%)
G1 (n 5 35)
G2 (n 5 35)
P
4 (11%)
10 (28%)
.133
Abbreviations: G1, patients submitted to cerebral reperfusion; G2, patients who did not receive cerebral reperfusion therapy. Odds ratio 5 .28 (.10-.78).
Abbreviations: G1, patients submitted to cerebral reperfusion; G2, patients who did not receive cerebral reperfusion therapy; %, occurrence of pneumonia. Odds ratio 5 .32 (.09-1.15).
ischemic stroke. The findings of our study demonstrate that individuals submitted to cerebral reperfusion therapy presented a lower degree of dysphagia compromise when compared with those who did not receive thrombolytic treatment. This result may be consistent from the physiological point of view, given that cerebral reperfusion therapy promotes restoration of blood flow and that tissue reperfusion in the shortest time produces reductions in neurologic deficiencies measured by the NIHSS and functional incapacity by mRS. Nevertheless, there are no reports on the effects of cerebral reperfusion therapy on oropharyngeal dysphagia.18,19 Although the patient group submitted to cerebral reperfusion therapy presented lower severity of dysphagia, both groups evolved with improvement in the daily oral intake rate but without statistical difference between them. These findings may indicate a positive effect from spontaneous recovery of neurologic functions based on the concept of neuroplasticity.20 In relation to severity, the patients not submitted to cerebral reperfusion therapy presented greater severity. Oropharyngeal dysphagia is known to be highly frequent in poststroke individuals and can affect 76%-91% of patients during hospitalization, persisting in about 50% at 6 months after the ischemic event.7 The evaluation of patients in the present study was restricted to the hospitalization period. Some studies from the literature show significant improvement of neurologic incapacity in prospective evaluations made 1 year after the stroke, although at 3 months a majority already show great recuperation.21 It is possible that in a more prospective analysis, we might also find greater benefits from cerebral reperfusion therapy in dysphagia.
The global rate of pneumonia in our study was 20%, whereas in diverse studies this incidence varies from 4.3% to 23% after stroke.22 In relation to the group of patients who received thrombolytic treatment, the pneumonia incidence was lower, which may be related to the lower degree of dysphagia in these individuals. However, in the literature, there are few works that describe the occurrence of pneumonia associated with stroke in patients submitted to cerebral reperfusion therapy.22-23 Fast reperfusion of cerebral tissue associated with metabolic control of neurons can contribute to diminished neurologic compromise, also linked to swallowing, reaffirming the clinical importance of this finding because of the elevated incidence of aspiration pneumonia in these individuals because of changes in their swallowing.9,15 Despite homogeneity in data analysis between groups, the main limitations of this study were the small sample number and lack of randomization because of the existence of a standard protocol for applying reperfusion treatment and follow-up time in our service unit. Furthermore, it is important that these individuals were admitted to the stroke unit, so they had access to follow-up by a speech therapist during the hospitalization to achieve medical conduct outcomes. Even so, this preliminary study is not only original but also clinically relevant. Our results indicate a favorable outcome in swallowing; however, we suggest the necessity for further studies with longer follow-up time to examine the functional impact of rt-PA. Therefore, based on our results, we can conclude that there is improvement of the oral intake rate in both groups, with lower severity of dysphagia and diminished pneumonia incidence in ischemic stroke patients submitted to cerebral reperfusion therapy.
Table 4. Evolution of the daily oral intake rate between the groups
Daily oral intake rate
Table 6. Relation between degrees of dysphagia and pneumonia among patients submitted to cerebral reperfusion Degrees of dysphagia
G1 (n 5 35)
G2 (n 5 35)
P
.14 (21.00-2.00)
.10 (.00-1.00)
.716
Abbreviations: G1, patients submitted to cerebral reperfusion; G2, patients who did not receive cerebral reperfusion therapy.
Pneumonia (%)
0-1 (n 5 18)
2-3 (n 5 17)
P
0 (0%)
4 (23%)
.045
0, absence of dysphagia; 1, mild dysphagia; 2, moderate dysphagia; 3, severe dysphagia; %, occurrence of pneumonia.
CEREBRAL REPERFUSION THERAPY AND DYSPHAGIA
5
References 1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation 2013;127:6-245. 2. Mansur AP, de Souza MFM, Favarato D, et al. Stroke and ischemic heart disease mortality trends in Brazil from 1979 to 1996. Neuroepidemiology 2003;22:179-183. 3. Cincura C, Pontes-Neto OM, Neville IS, et al. Stroke Scale, Modified Rankin Scale and Barthel Index in Brazil: the role of cultural adaptation and structured interviewing. Cerebrovasc Dis 2009;27:119-122. 4. Lotufo PA, Bense~ nor IM. Trends of stroke subtypes mortality in Sao Paulo, Brazil (1996-2003). Arq Neuropsiquiatr 2005;63:951-955. 5. Lawrence ES, Coshall C, Dundas R, et al. Estimates of the prevalence of acute stroke impairments and disability in a multiethnic population. Stroke 2001;32:1279-1284. 6. Daniels SK, Brailey K, Priestly DH, et al. Aspiration in patients with acute stroke. Arch Phys Med Rehabil 1998; 79:14-19. 7. Schelp AO, Cola PC, Gatto AR, et al. Incidence of oropharyngeal dysphagia associated with stroke in a regional hospital in S~ao Paulo State—Brazil. Arq Neuropsiquiatr 2004;62:503-506. 8. Martino R, Foley N, Bhogal S, et al. Dysphagia after stroke: incidence, diagnosis, and pulmonary complications. Stroke 2005;36:2756-2763. 9. Katzan IL, Cebul RD, Husak SH, et al. The effect of pneumonia on mortality among patients hospitalized for acute stroke. Neurology 2003;60:620-625. 10. Wilson RD. Mortality and cost of pneumonia after stroke for different risk groups. J Stroke Cerebrovasc Dis 2012; 21:61-67. 11. Crary MA, Humphrey JL, Carnaby-Mann G, et al. Dysphagia, nutrition, and hydration in ischemic stroke patients at admission and discharge from acute care. Dysphagia 2013;28:69-76. 12. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
Stroke rt-PA Stroke Study Group. N Engl J Med 1995; 333:1581-1587. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;359:1317-1329. Ott D, Hodge R, Pikna LA, et al. Modified barium swallow: clinical and radiographic correlation and relation to feeding recommendations. Dysphagia 1996;11:187-190. Crary MA, Mann GD, Groher ME. Initial psychometric assessment of a Functional Oral Intake Scale for dysphagia in stroke patients. Arch Phys Med Rehabil 2005;86:1516-1520. Hilker R, Poetter C, Findeisen N, et al. Nosocomial pneumonia after acute stroke: implications for neurological intensive care medicine. Stroke 2003;34:975-981. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008;36:309-332. Okubo PC, F abio SR, Domenis DR, et al. Using the National Institute of Health Stroke Scale to predict dysphagia in acute ischemic stroke. Cerebrovasc Dis 2012;33:501-507. Blinzler C, Breuer L, Huttner HB, et al. Characteristics and outcome of patients with early complete neurological recovery after thrombolysis for acute ischemic stroke. Cerebrovasc Dis 2011;31:185-190. Barritt AW, Smithard DG. Role of cerebral cortex plasticity in the recovery of swallowing function following dysphagic stroke. Dysphagia 2009;24:83-90. Urra X, Ari~ no H, Llull L, et al. The outcome of patients with mild stroke improves after treatment with systemic thrombolysis. PLoS One 2013;8:e59420. Hannawi Y, Hannawi B, Rao CP, et al. Stroke-associated pneumonia: major advances and obstacles. Cerebrovasc Dis 2013;35:430-443. Scheitz JF, Endres M, Heuschmann PU, et al. Reduced risk of poststroke pneumonia in thrombolyzed stroke patients with continued statin treatment. Int J Stroke 2012; http:// dx.doi.org/10.1111/j.1747-4949.2012.00864.x [Epub ahead of print].
Background: The high prevalence of dysphagia after stroke leads to increased mortality, and cerebral reperfusion therapy has been effective in reducing neurologic deficits. The aim of this study was to investigate the severity and evolution of dysphagia and the occurrence of pneumonia in patients submitted to cerebral reperfusion therapy. Methods: Seventy ischemic stroke patients were evaluated. Of these, 35 patients (group 1) were submitted to cerebral reperfusion therapy and 35 (group 2) did not receive thrombolytic treatment. The following were evaluated: severity of dysphagia by means of videofluoroscopy, evolution of oral intake rate by means of the Functional Oral Intake Scale, and the occurrence of pneumonia by international protocol. The relation between the severity of dysphagia and the occurrence of pneumonia with the treatment was evaluated through the chi-square test; the daily oral intake rate and its relation to the treatment were assessed by the Mann–Whitney test and considered significant if P is less than .05. Results: The moderate and severe degrees of dysphagia were more frequent (P 5 .013) among the patients who were not submitted to cerebral reperfusion therapy. The daily oral intake evolved independently of the treatment type, without statistical significance when compared between the groups, whereas pneumonia occurred more frequently in group 2 (28%) in relation to group 1 (11%) and was associated with the worst degrees of dysphagia (P 5.045). Conclusions: We can conclude that there is improvement in the oral intake rate in both groups, with lower severity of dysphagia and occurrence of pneumonia in ischemic stroke patients submitted to cerebral reperfusion therapy. Key Words: Stroke—thrombolytic therapy—deglutition—deglutition disorders—dysphagia. Ó 2014 by National Stroke Association
Introduction From the *Neurology Service, Botucatu School of Medicine, University Estadual Paulista J ulio de Mesquita Filho, S~ao Paulo; †Department of Phonoaudiology, School of Pholosophy and Sciences, Marılia; and ‡Department of Surgery, Botucatu School of Medicine, University Estadual Paulista J ulio de Mesquita Filho, S~ ao Paulo, Brazil. Received November 13, 2013; accepted December 19, 2013. Grant support: None. Address correspondence to Gustavo J. Luvizutto, MSc, Botucatu School of Medicine, University Estadual Paulista J ulio de Mesquita Filho, District of Rubi~ao Junior, Botucatu, SP 18618-970, Brazil. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2014 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.12.033
Each year around 610,000 individuals have a stroke, which is one of the 3 main causes of death in countries around the world.1 In Brazil, it is the main cause of death in the adult population and responsible for 10% of all hospital admissions.2-4 As well as a high mortality index, ischemic stroke can cause communication and swallowing disorders, with a significant impact on an individual’s functional evolution.5 The incidence of oropharyngeal dysphagia is high, ranging between 51% and 91% in acute and subacute stroke phases.6-8 Dysphagia when associated with aspiration pneumonia can prolong hospital stay and increase mortality risk 3-fold.9,10 Early identification and
Journal of Stroke and Cerebrovascular Diseases, Vol. -, No. - (---), 2014: pp 1-5
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P.W. RIBEIRO ET AL.
2
treatment of dysphagia can reduce the risks of pulmonary, nutritional, and hydration complications and reduce hospital stay. It is, therefore, vital that effective treatment is given early to help reduce expected stroke sequelae. The swallowing evaluation aims to identify the presence of dysphagia and proposes the most secure alimentation route in the acute stroke phase.11 The advent of new treatment approaches in acute stroke phase has brought about prognostic and functional advances for the individual, including cerebral reperfusion therapy, a procedure described as capable of restoring blood flow by intravenous recombinant tissue plasminogen activator (rt-PA) infusion. Recent studies have shown that, when performed in the first 4.5 hours after symptom appearance, cerebral reperfusion therapy produces a significant reduction of functional incapacity, as measured by the modified Rankin Scale (mRS) and improvement of neurologic capacity, by the National Institutes of Health Stroke Scale (NIHSS) score in the first 24 hours. Furthermore, 31%-50% of rt-PA–treated cases show neurologic recuperation after 3 months.12,13 Even though oropharyngeal dysphagia is described as one of the high mortality sequelae in patients after stroke, there is no evidence in the literature of a therapeutic effect of cerebral reperfusion on swallowing. The present study aimed to investigate the severity and evolution of dysphagia and the incidence of pneumonia in patients submitted to cerebral reperfusion therapy. The central hypothesis of this study was to demonstrate that cerebral reperfusion therapy diminishes the severity of dysphagia, improves the oral intake rate, and reduces the pneumonia incidence after ischemic stroke.
Methods This was a prospective cohort study in ischemic stroke patients of both sexes, confirmed by cranial computerized tomography during hospitalization, under conservative or thrombolytic treatment in the stroke unit at the Botucatu School of Medicine University Hospital—UNESP (Univ Estadual Paulista), SP, Brazil. Patients were excluded if they presented hemorrhagic or posterior circulation stroke, previous mRS score greater than 1, preexisting dementia, unstable clinical, another neurologic disease, or had undergone decompressive hemicraniectomy. The study was approved by the Human Research Ethics Committee under directive 3496/2010, and all individuals gave their consent to participate in the study.
Procedures Patients were divided into 2 groups according to the neurologic treatment received during acute stroke phase. Group 1 was constituted by patients submitted to cerebral reperfusion therapy with intravenous rt-PA (.9 mg/kg), and group 2 by patients who did not receive cerebral re-
perfusion therapy on account of presenting at least one of the following exclusion criteria for thrombolysis: another stroke or serious head trauma within the preceding 3 months, major surgery within 14 days, history of intracranial hemorrhage, systolic blood pressure greater than 185 mm Hg, or diastolic blood pressure greater than 110 mm Hg; rapidly improving or minor symptoms; symptoms suggestive of subarachnoid hemorrhage; gastrointestinal hemorrhage or urinary tract hemorrhage within the previous 21 days; arterial puncture at a no compressible site within the previous 7 days; or seizure at the onset of stroke. All patients were monitored for clinical parameters (blood glucose, temperature, and arterial pressure) at the stroke unit.
Evaluation of Dysphagia Dysphagia was evaluated by means of videofluoroscopic recordings, using foods modified with barium sulfate. The exam was initiated by offering a pasty food, followed by a liquid. It is important to emphasize that the evolution of the offering’s quantity and consistency was directly dependent on the performance of the patient in the previous deglutition, with the exam being interrupted when the presence of laryngotracheal aspiration was observed. For the exam, the patient was advised to remain in a lateral position, which allows visualization of the upper and lower anatomical limits, from the oral cavity to the esophagus. From the exam analysis, the severity of dysphagia classifies dysphagia in 3 levels, defined as follows14: degree 1, mild (oral alterations without laryngeal penetration and/or laryngotracheal aspiration); degree 2, moderate (oral alterations, pharyngeal residues, and little penetration or laryngotracheal aspiration of a determinate consistency); and degree 3, severe (substantial laryngotracheal aspiration or failure to swallow). The patients with an absence of dysphagia were classified as degree 0.
Evolution of Daily Oral Intake Rate All patients were evaluated by the Functional Oral Intake Scale (FOIS), which classifies the quantity of oral intake into 7 specific levels: 1, nothing by mouth; 2, other route dependent on minimal oral attempts to ingest food or liquid; 3, other route dependent on some oral intake of food or liquid; 4, total oral diet of a single consistency; 5, total oral diet with multiple consistencies but requiring special preparation or compensations; 6, total oral diet with multiple consistencies without special preparation but with specific food limitations; and 7, total oral diet with no restrictions. Level 0 was established for patients who were fasting at initial evaluation.15 FOIS was initially applied by a speech therapist before and after videofluoroscopy and at discharge from the hospital. Patients were monitored during hospital stay with diet being modified when indicated and by interim re-
CEREBRAL REPERFUSION THERAPY AND DYSPHAGIA
evaluations, according to neurologic evolution. The rate of daily evolution was based on the relation between FOIS after videofluoroscopy (FOIS1) and hospital discharge (FOIS2), as a function of the time of hospitalization (th), according to the following calculation: (FOIS1 2 FOIS2/th).
Pneumonia The data on pneumonia were obtained by clinical, radiological, and laboratory evaluation during hospitalization, according to international protocol.16,17
Statistical Analysis To evaluate the relation between the dysphagia severity and the treatment received, the potential confounders were analyzed by logistic regression, whereas the relation between group 1 and group 2 was assessed by chi-square test. To evaluate the daily rate of oral intake and its relation to treatment, the Mann–Whitney test was used, whereas the incidence of pneumonia and its relation to the dysphagia degree were analyzed by chi square and considered significant if P is less than .05. Based on the dysphagia frequencies observed in both groups, it can be estimated that the power of the test is about 70%, supposing, for the effect of calculation, simple random sampling, type I error probability 5 .05, and the absence of confounding effects.
Results Between April 2011 and December 2012, 70 individuals neurologically diagnosed with ischemic stroke were divided into 2 groups of 35 patients each. The clinical and demographic data are presented in Table 1. Table 2 shows the absence of a significant relation between clinical and demographic data versus the dysphagia degree, so that the relation between treatment and dysphagia degree was analyzed without the necessity of considering any of the earlier mentioned variables, demonstrating the homogeneity between the groups. Table 3 shows a significant relation between treatment and dysphagia degree, with degrees 2 (moderate) and 3 (severe) being significantly more frequent (P 5 .013) among the patients
3
Table 1. Demographic data for thrombolysed and nonthrombolysed patient groups G1 (n 5 35)
G2 (n 5 35)
66.5 17 72.4 1.69 23.5 18 17 0 12.4 (4-22) 5.4 (1-17) 4.9
68.3 19 71.3 1.71 26.2 17 18 0 11.6 (1-24) 8 (1-17) 3.7
10.1
13.6
Variables* Age (y) Sex, male Weight (kg) Height (m) BMI (kg/m2) Right hemisphere Left hemisphere Previous mRS NIHSS at admission NIHSS at evaluation Ictus (admission to evaluation) (d) Time in hospital (d)
Abbreviations: BMI, body mass index; G1, patients submitted to cerebral reperfusion; G2, patients who did not receive cerebral reperfusion therapy; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale. *Numbers are mean (SD) or counts (%).
who were not submitted to cerebral reperfusion therapy (group 2). There was evolution of the daily oral intake rate independently of the treatment type, but it did not differ statistically between the groups (Table 4). The pneumonia rate among the studied patients during hospitalization was 20%. Table 5 shows that, despite not being statistically significant, the occurrence of pneumonia was more frequent in group 2 patients than group 1 (28% versus 11%). Table 6 shows that pneumonia was more frequent among the patients with the worst degrees of dysphagia being that, among those patients submitted to reperfusion, the relation between dysphagia degree and pneumonia was significant (P 5 .045).
Discussion Cerebral reperfusion therapy has been shown to improve immediate and long-term patient recovery after
Table 2. Relation between clinical and demographic data Variable
b
SE
Wald
P
OR (95% CI)
Age (y) Topography of lesion NIHSS at admission FOIS at admission Constant
.01 .90 .03 2.23 2.07
.02 .62 .06 .16 1.72
.39 2.06 .19 2.20 .00
.531 .152 .664 .138 .967
1.01 (.97-1.06) 2.45 (.72-8.33) 1.03 (.91-1.16) .79 (.58-1.08) .93
Abbreviations: CI, confidence interval; FOIS, Functional Oral Intake Scale; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; Wald, Wald test. b indicates estimated coefficient.
P.W. RIBEIRO ET AL.
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Table 3. Relation between treatment and degrees of dysphagia Degrees of dysphagia G1 (n 5 35) G2 (n 5 35) 0-1 2-3
18 (51%) 17 (49%)
8 (23%) 27 (77%)
Table 5. Comparison between treatments in relation to the percentage of patients with pneumonia
P .013
Pneumonia (%)
G1 (n 5 35)
G2 (n 5 35)
P
4 (11%)
10 (28%)
.133
Abbreviations: G1, patients submitted to cerebral reperfusion; G2, patients who did not receive cerebral reperfusion therapy. Odds ratio 5 .28 (.10-.78).
Abbreviations: G1, patients submitted to cerebral reperfusion; G2, patients who did not receive cerebral reperfusion therapy; %, occurrence of pneumonia. Odds ratio 5 .32 (.09-1.15).
ischemic stroke. The findings of our study demonstrate that individuals submitted to cerebral reperfusion therapy presented a lower degree of dysphagia compromise when compared with those who did not receive thrombolytic treatment. This result may be consistent from the physiological point of view, given that cerebral reperfusion therapy promotes restoration of blood flow and that tissue reperfusion in the shortest time produces reductions in neurologic deficiencies measured by the NIHSS and functional incapacity by mRS. Nevertheless, there are no reports on the effects of cerebral reperfusion therapy on oropharyngeal dysphagia.18,19 Although the patient group submitted to cerebral reperfusion therapy presented lower severity of dysphagia, both groups evolved with improvement in the daily oral intake rate but without statistical difference between them. These findings may indicate a positive effect from spontaneous recovery of neurologic functions based on the concept of neuroplasticity.20 In relation to severity, the patients not submitted to cerebral reperfusion therapy presented greater severity. Oropharyngeal dysphagia is known to be highly frequent in poststroke individuals and can affect 76%-91% of patients during hospitalization, persisting in about 50% at 6 months after the ischemic event.7 The evaluation of patients in the present study was restricted to the hospitalization period. Some studies from the literature show significant improvement of neurologic incapacity in prospective evaluations made 1 year after the stroke, although at 3 months a majority already show great recuperation.21 It is possible that in a more prospective analysis, we might also find greater benefits from cerebral reperfusion therapy in dysphagia.
The global rate of pneumonia in our study was 20%, whereas in diverse studies this incidence varies from 4.3% to 23% after stroke.22 In relation to the group of patients who received thrombolytic treatment, the pneumonia incidence was lower, which may be related to the lower degree of dysphagia in these individuals. However, in the literature, there are few works that describe the occurrence of pneumonia associated with stroke in patients submitted to cerebral reperfusion therapy.22-23 Fast reperfusion of cerebral tissue associated with metabolic control of neurons can contribute to diminished neurologic compromise, also linked to swallowing, reaffirming the clinical importance of this finding because of the elevated incidence of aspiration pneumonia in these individuals because of changes in their swallowing.9,15 Despite homogeneity in data analysis between groups, the main limitations of this study were the small sample number and lack of randomization because of the existence of a standard protocol for applying reperfusion treatment and follow-up time in our service unit. Furthermore, it is important that these individuals were admitted to the stroke unit, so they had access to follow-up by a speech therapist during the hospitalization to achieve medical conduct outcomes. Even so, this preliminary study is not only original but also clinically relevant. Our results indicate a favorable outcome in swallowing; however, we suggest the necessity for further studies with longer follow-up time to examine the functional impact of rt-PA. Therefore, based on our results, we can conclude that there is improvement of the oral intake rate in both groups, with lower severity of dysphagia and diminished pneumonia incidence in ischemic stroke patients submitted to cerebral reperfusion therapy.
Table 4. Evolution of the daily oral intake rate between the groups
Daily oral intake rate
Table 6. Relation between degrees of dysphagia and pneumonia among patients submitted to cerebral reperfusion Degrees of dysphagia
G1 (n 5 35)
G2 (n 5 35)
P
.14 (21.00-2.00)
.10 (.00-1.00)
.716
Abbreviations: G1, patients submitted to cerebral reperfusion; G2, patients who did not receive cerebral reperfusion therapy.
Pneumonia (%)
0-1 (n 5 18)
2-3 (n 5 17)
P
0 (0%)
4 (23%)
.045
0, absence of dysphagia; 1, mild dysphagia; 2, moderate dysphagia; 3, severe dysphagia; %, occurrence of pneumonia.
CEREBRAL REPERFUSION THERAPY AND DYSPHAGIA
5
References 1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation 2013;127:6-245. 2. Mansur AP, de Souza MFM, Favarato D, et al. Stroke and ischemic heart disease mortality trends in Brazil from 1979 to 1996. Neuroepidemiology 2003;22:179-183. 3. Cincura C, Pontes-Neto OM, Neville IS, et al. Stroke Scale, Modified Rankin Scale and Barthel Index in Brazil: the role of cultural adaptation and structured interviewing. Cerebrovasc Dis 2009;27:119-122. 4. Lotufo PA, Bense~ nor IM. Trends of stroke subtypes mortality in Sao Paulo, Brazil (1996-2003). Arq Neuropsiquiatr 2005;63:951-955. 5. Lawrence ES, Coshall C, Dundas R, et al. Estimates of the prevalence of acute stroke impairments and disability in a multiethnic population. Stroke 2001;32:1279-1284. 6. Daniels SK, Brailey K, Priestly DH, et al. Aspiration in patients with acute stroke. Arch Phys Med Rehabil 1998; 79:14-19. 7. Schelp AO, Cola PC, Gatto AR, et al. Incidence of oropharyngeal dysphagia associated with stroke in a regional hospital in S~ao Paulo State—Brazil. Arq Neuropsiquiatr 2004;62:503-506. 8. Martino R, Foley N, Bhogal S, et al. Dysphagia after stroke: incidence, diagnosis, and pulmonary complications. Stroke 2005;36:2756-2763. 9. Katzan IL, Cebul RD, Husak SH, et al. The effect of pneumonia on mortality among patients hospitalized for acute stroke. Neurology 2003;60:620-625. 10. Wilson RD. Mortality and cost of pneumonia after stroke for different risk groups. J Stroke Cerebrovasc Dis 2012; 21:61-67. 11. Crary MA, Humphrey JL, Carnaby-Mann G, et al. Dysphagia, nutrition, and hydration in ischemic stroke patients at admission and discharge from acute care. Dysphagia 2013;28:69-76. 12. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
Stroke rt-PA Stroke Study Group. N Engl J Med 1995; 333:1581-1587. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;359:1317-1329. Ott D, Hodge R, Pikna LA, et al. Modified barium swallow: clinical and radiographic correlation and relation to feeding recommendations. Dysphagia 1996;11:187-190. Crary MA, Mann GD, Groher ME. Initial psychometric assessment of a Functional Oral Intake Scale for dysphagia in stroke patients. Arch Phys Med Rehabil 2005;86:1516-1520. Hilker R, Poetter C, Findeisen N, et al. Nosocomial pneumonia after acute stroke: implications for neurological intensive care medicine. Stroke 2003;34:975-981. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008;36:309-332. Okubo PC, F abio SR, Domenis DR, et al. Using the National Institute of Health Stroke Scale to predict dysphagia in acute ischemic stroke. Cerebrovasc Dis 2012;33:501-507. Blinzler C, Breuer L, Huttner HB, et al. Characteristics and outcome of patients with early complete neurological recovery after thrombolysis for acute ischemic stroke. Cerebrovasc Dis 2011;31:185-190. Barritt AW, Smithard DG. Role of cerebral cortex plasticity in the recovery of swallowing function following dysphagic stroke. Dysphagia 2009;24:83-90. Urra X, Ari~ no H, Llull L, et al. The outcome of patients with mild stroke improves after treatment with systemic thrombolysis. PLoS One 2013;8:e59420. Hannawi Y, Hannawi B, Rao CP, et al. Stroke-associated pneumonia: major advances and obstacles. Cerebrovasc Dis 2013;35:430-443. Scheitz JF, Endres M, Heuschmann PU, et al. Reduced risk of poststroke pneumonia in thrombolyzed stroke patients with continued statin treatment. Int J Stroke 2012; http:// dx.doi.org/10.1111/j.1747-4949.2012.00864.x [Epub ahead of print].
