Characteristics of Research Subjects
The incidence of gastrointestinal bleeding in this study was 24%. This incidence is higher than other studies in the world, including the United States (1.2%), Japan (1.4%), Canada (1.5%), China (1.5%), Malaysia (5.2 %), Philippines (7%) and Taiwan (7.8%). Research in Taiwan says Asian races have more bleeding than Caucasians associated with Helicobacter pylori infection. Research in Indonesia, Taiwan, the Philippines, and Malaysia was only in one hospital, while in the United States, Japan, Canada, and China multicentre studies so that there were differences in the number of subjects. In addition, this difference may be due to differences in the operational definition of gastrointestine bleeding l. In developed countries, endoscopic examination is the gold standard for the diagnosis of gastrointetinal bleeding, whereas in this study only based on clinical findings.7,11,12
This study showed the proportion of women who experienced gastrointestinal bleeding was slightly more than men (54.2% vs 45.8%), but no significant difference was found. Conversely there was a significant difference in China and Taiwan where men were more at risk of developing gastrointestinal bleeding. This might be due to differences in the characteristics and number of research subjects.10,12
The average age of the study subjects was younger (58 years) compared to the stroke register in Indonesia (65 years), Chinese (66 years), Taiwan (69 years). This might be due to differences in the characteristics and number of research subjects. Another reason is that Indonesia is a developing country that experiences unhealthy lifestyle changes that increases risk factors for stroke such as hypertension and diabetes mellitus. The age of subjects with gastrointestinal bleeding was older compared to those without gastrointetinal bleeding (61 vs 58 years) according to the study in Taiwan (74 vs 69 years), Japanese (76 vs 73 years), Canada (75 vs 72 years). This is because at an older age the physiological function of the gastrointestinal system decreases. This causes a decrease in the function of protective cells in the gastrointestinal system so that bleeding occurs more easily.7,13,14
This study showed the risk factors for dyslipidemia were slightly lower in subjects with gastrointestinal bleeding (54.1%) compared to those without gastrointestinal bleeding (60.5%). This is consistent with previous studies in Japan (29.2% vs 49.6%), Canada (18% vs 34%). The cause of this event is not yet fully known, but previous studies say it might be due to the use of antibiotics for eradicating bacteria, especially Helicobacter pylori. Such eradication may be related to an increase in serum cholesterol or triglycerides.
Subjects with gastrointestinal bleeding had atrial fibrillation risk factors and embolic stroke type than those without gastrointestinal bleeding (25% vs 5.2% and 66.7% vs. 42.1%). This is because in embolic strokes there is a widespread brain ischemic so that the neuroinflammation in the brain gets more intense. The inflammatory mediator involves activating the cervico-vagal nerve pathway which will activate parasympathetic pathway to produce acetylcholine vagal hyperactivity. This vagal hyperactivity stimulates production of acid chloride in gastric causing gastrointestinal bleeding. Previous research in Japan (36%) and Canada (20%) showed the same cases.
Subjects with gastrointestinal bleeding had a history of peptic ulcer / gastrointestinal bleeding and the use of antiplatelet / anticoagulant therapy before admission was slightly more than without gastrointestinal bleeding (20.8% vs 0 and 29.2% vs. 11.8%). These results are in line with previous studies in Taiwan, Japan, the United States, and Canada. This is because the use of antiplatelet is associated with damage to the gastric epithelium directly and inhibits the production of prostaglandin by the gastric mucosa, causing gastric ulcers. The use of anticoagulants is related to the systemic effects caused by inhibition of clotting factors involving vitamin K.11,15,16
Subjects with gastrointestinal bleeding had a higher NIHSS score at admission compared to those without gastrointestinal bleeding (16 vs 7). The results of this study are in accordance with other studies in Japan. GCS scores at admission are lower in subjects with gastrointestinal bleeding (12) compared to those without gastrointestinal bleeding (15). This is related to the severity of the ischemic stroke that occurs. The median mRS score before admission did not differ between subjects with bleeding and without bleeding. This is caused by the severity of the stroke that occurred before is relatively mild.
Subjects with gastrointestinal bleeding had more infections than without bleeding (54.2% vs 18.4%). Research in Taiwan (79.2% vs. 19.1%) and the United States (5.2% vs 1%) showed similar results. Gastrointestinal bleeding causes infection to be under debate. There are several hypotheses which state that the severity of ischemic stroke causes gastrointestinal bleeding. Nosocomial infections that occur due to disability in the stroke. Another opinion said the infection caused gastrointestinal bleeding due to changes in faktor coagulation due to inflammation that occurs.11,17
Relationship to Gastrointestinal Bleeding with Survival
This study showed gastrointestinal bleeding significantly affected the incidence of death in acute ischemic stroke patients (p = 0.021). The risk of death is 3.2 times greater in gastrointestinal bleeding than without bleeding. The results of this analysis have been controlled by confounding infection variables. Although the risk of death in infection is higher (3.9 times), the focus of this study is gastrointestinal bleeding. Based on these results, gastrointestinal bleeding plays an important role in survival without being influenced by infection.
Infection is considered to be a confounding variable because in several studies in Taiwan, the United States, Brazil and Poland, infection significantly affected mortality in acute ischemic stroke patients. Extensive ischemic stroke causes an increase in catecholamines through the sympathetic system. The increase in catecholamines causes suppression of the immune system through neutrophil malfunction, making it easier to get an infection.9,11,18
Research in Japan said the mortality of subjects with gastrointestinal bleeding was higher than without bleeding (15.7% vs 1.9%) with a risk of death 8.7 times. In Canada, the mortality of subjects with gastrointestinal bleeding was 28% with a risk of death 1.5 times greater than without bleeding. Research in the United States showed that as many as 16.1% of subjects with gastrointestinal bleeding died with a risk of death 1.8 times greater than without bleeding. Based on these data, gastrointestinal bleeding significantly affected death in patients with acute ischemic stroke.11
Stratification analysis based on the presence or absence of infection diagnosis showed that subjects with infections who subsequently had gastrointestinal bleeding had a lower risk of death than those without infection and then had gastrointestinal bleeding (1.7 times vs. 22.5 times).
In addition there were 10 patients without gastrointestinal bleeding who were given prophylactic therapy (PPI, histamine H2 antagonist, or cytoprotectic agent), where only 1 subject died due to sepsis.
Relationship to Gastrointestinal Bleeding with Length of Stay
This study showed subjects with gastrointestinal bleeding were treated more than 7 days (75%) compared with no gastrointestinal bleeding (32.9%). The risk of treatment is 1.8 times longer in subjects with gastrointestinal bleeding than without bleeding after being controlled by confounding infection variables. Although the risk of long-term treatment for infection is higher (2.2 times), the focus of this study is gastrointestinal bleeding. Based on these results, gastrointestinal bleeding plays an important role in the length of care without infection. Infection is considered a confounding variable because previous studies in Taiwan, the United States, Denmark, and the United Kingdom mentioned infection affecting the length of stay in acute ischemic stroke patients. 11,19
The results of this study are in accordance with previous studies in the United States. Research in the United States found that ischemic stroke patients with gastrointestinal bleeding had a longer average length of stay (11 days) than without gastointestinal bleeding (5 days) with a 2.3 times longer risk of treatment. Patient care was longer due to examination and therapy. additions were made to patients with gastrointestinal bleeding such as delaying antiplatelet / anticoagulant initial therapy, blood transfusion, and endoscopy to find gastrointestinal bleeding sources. Based on these data, gastrointestinal bleeding has a significant effect on prolonging the length of treatment in acute ischemic stroke patients (p = 0.008) .11
Stratification analysis based on the presence or absence of infection diagnosis showed that subjects with infections who subsequently experienced gastrointestinal bleeding had a long risk of treatment not much different than those without infection and then had gastrointestinal bleeding (1.5 times vs. 2 times).
This study used clinical symptoms to diagnose gastrointestinal bleeding from brownish NGT hose, not confirmed by endoscopy to find the source of bleeding and Helicobacter pylori infection. This study did not take into account antiplatelet administration, anticoagulants, or other drugs that might affect the gastrointestinal tract during hospital treatment.