VIETNAM MILITARY MEDICAL UNIVERSITYLE MINH DUNG CLINICAL, SUBCLINICAL CHARACTERISTICS AND FACTORS ASSOCIATED WITH GASTROINTESTINAL BLEEDING IN DENGUE PEDIATRIC PATIENTS Major: Internal m
Trang 1VIETNAM MILITARY MEDICAL UNIVERSITY
LE MINH DUNG
CLINICAL, SUBCLINICAL CHARACTERISTICS AND FACTORS ASSOCIATED WITH GASTROINTESTINAL BLEEDING IN DENGUE PEDIATRIC PATIENTS
Major: Internal medicine
SUMMARY OF DOCTORAL DISSERTATION
HA NOI-2020
Trang 21 Nguyen Duy Thang, Ph.D., Associate Professor
2 Nguyen Quang Duat, Ph.D., Associate Professor.
Reviewer 1: Dao Van Long, Ph.D., Professor
Reviewer 2: Nguyen Van Kinh, Ph.D., Professor
Reviewer 3: Vu Van Khien, Ph.D., Associate Professor
The dissertation was protected at the school-level council
At …… , ……… 2020
The dissertation can be found in:
1 Vietnam National Library.
Trang 4of death among the most common infectious diseases.
The clinical and subclinical characteristics of Denguehemorrhagic fever in children are diverse causing difficulties indiagnosing Bleeding in general and gastrointestinal bleeding, inparticular, are common symptoms in Dengue patients who havewarning signs and shock Children with severe or prolonged shockusually have severe bleeding
To improve the effectiveness of early detection, givingprognosis and intervention for Dengue-infectied pediatric patients,
we conducted the study with the following aims:
1 To assess clinical and subclinical characteristics of Dengue pediatric patients with gastrointestinal bleeding in Nhi Dong 1 Hospital from 12/2014 to 12/2015.
2 To evaluate the relationship between gastrointestinal bleeding and clinical, subclinical characteristics and virus type of Dengue pediatric patients at Nhi Dong 1 Hospital from 12/2014 to 12/2015.
Trang 5New contributions to the dissertation:
This is the first study in Vietnam to conduct with complete,systematic, detailed information about gastrointestinal (GI) bleeding inDengue pediatric patients The study has shown some clinical,subclinical characteristics of gastrointestinal bleeding in Denguepediatric patients In which the main symptoms are abdominal pain(78%) and fatigue (74.6%) In addition, the most common symptoms arevomiting blood (hematemesis) (93.2%) and blood in the stomach sonde(86.4%) and abdominal pain (78%) The common subclinical symptomsare PT rate < 60% ( 81.3%) and APTT time > 60 seconds (81.4%)
The study identified some factors associated with GI bleeding inDengue pediatric patients There are 3 related symptoms: abdominal pain,lethargy, fatigue In addition, 5 physical symptoms that were related to GIbleeding on univariate analysis are vomiting, bloating, neurologicaldisorders, edema, and nasal bleeding There were 2 subclinical symptoms:
PT rate < 60% and APTT time > 60 seconds, more common andstatistically significant differences between GI bleeding and GI non-bleeding group (p <0.05) The GI bleeding group is mainly found in type
2, accounting for 66.1% There are 2 clinical symptoms (abdominalobstruction and edema) in patients with GI bleeding appearing with asignificantly higher incidence in type 2 than type 1
Dissertation structure
A total of 117 pages including 2-pages of issue sets; Chapter 1 isOverview of 33 pages; Chapter 2 is Object and Methodology having
19 pages; Chapter 3 is Research Results including 28 pages; Chapter
4 is Discussion 32 pages; Conclusion lasts 2 pages and the last pagefor the proposal
The thesis has 41 tables, 7 figures and 6 charts, 122 references
Trang 6Chapter 1: OVERVIEW 1.1 Overview of gastrointestinal bleeding
1.1.1 Characteristics of gastrointestinal bleeding
Epidemiological characteristics of gastrointestinal bleeding
Acute gastrointestinal (GI) bleeding is a major cause ofhospitalization in the United States estimated 300,000 patientsannually An annual incidence of upper GI bleeding is 40-150 per100,000 people and the mortality rate accounts for 6-10%; while inlower GI bleeding, that incidence is 20-27 per 100,000 people andthe mortality rate is 4% -10%
In adults, the most common cause of GI bleeding is a duodenal ulcer, accounting for 50% of GI bleeding cases in which therate of duodenal ulcer is higher than gastric ulcer
gastric-1.1.2 Characteristics of gastrointestinal bleeding in children
1.1.2.1 Epidemiological characteristics of gastrointestinal bleeding
in pediatric patients
Up to 95% of upper GI bleeding cases in children areassociated with GI mucosa damaging and esophageal varices Unlikeupper GI bleeding, many cases of lower GI bleeding usually cease.Bancroft et al determined that vomiting blood accounted for only 5%
of patients (327 of 6,337) with indications for gastroduodenalendoscopy in children According to Bensouda et al., a study in Frenchpopulation estimates that upper GI bleeding occurs in 1 to 2 childrenper 10,000 children per year Among that, exposure to nonsteroidalanti-inflammatory drugs (NSAIDs) plays a role in 36% of these cases
1.1.2.2 Clinical and subclinical characteristics of gastrointestinal bleeding in Dengue pediatric patients
Trang 7Not only the symptoms of Dengue hemorrhagic fever, butother signs below also suggest upper GI bleeding:
Signs: There are often warning signs, especially in older children Clinical signs:
- Vomiting blood; bloody stools
- Initial clinical assessment: a quick assessment of generalcondition especially the vital signs and level of their consciousness
- Severe GI bleeding has the following symptoms: fast pulse;low blood pressure; pale in skin color; sweatings and cold limbs;signs of cerebral ischemia; and shock
Subclinical signs:
- Tests: full blood count; prothrombin time and thromboplastintime, fibrinogen; blood type identification; liver function test (AST,ALT, protein, and albumin), renal function test (urea and creatinine)
- Angiography, radionuclide scan, gastroduodenal endoscopy, andcolonoscopy
1.1.2.3 Definitive and differential diagnosis of gastrointestinal bleeding in pediatric patients
Definitive diagnosis:
Determine the blood in the substance of vomiting or stool
"Bedside technique" to determine hemoglobin (eg Hemocult,Gastrocult, SmithKline Diagnostics) or quick test of Fecal OccultBlood - FOB to determine blood in the stool
Differential diagnosis:
Vomiting blood: GI bleeding should be differentiated from thelesions that cause bleeding in the nose and throat
Trang 8Children with black feces also need to distinguish fromchildren taking drugs that make black feces (bismuth, iron, activatedcarbon) or constipation for a long time.
1.1.2.4 Diagnosis causes of gastrointestinal bleeding by age group
Upper GI bleeding due to various reasons, especially by agegroup Common gastric ulcer, rupture of the esophagus varies,Mallory - Weiss, gastroesophageal reflux It can be divided into threegroups
Lower GI bleeding: Common intussusception, Meckel’sdiverticulum, anal fissure, polyps in the colon, vascularmalformation
1.2 Dengue hemorrage fever characteristics in pediatric patients
1.2.1 The characteristics of Dengue hemorrhagic fever in pediatric patients
Dengue hemorrhagic fever has a variety of clinicalmanifestations, rapid progression The disease usually starts suddenlyand progresses through three stages: the fever stage, the dangerousstage, and the recovery phase
According to WHO (2009), the disease was divided into threelevels: Dengue hemorrage fever, Dengue hemorrage fever withwarning signs, severe Dengue hemorrage fever
1.2.2 Pathogenesis of Dengue hemorrhagic fever and gastrointestinal bleeding in Dengue hemorrhagic fever
Although many researchers around the world have researcheddeeply on the virology and pathogenesis of dengue fever, there hasbeen no consensus to date Currently refers to the followingphenomena: plasma leakage due to increased vascular permeability,coagulopathy, and liver damage during Dengue hemorrhagic fever
Trang 91.2.3 Relationship between Dengue virus type and gastrointestinal bleeding
Recent studies indicate that different types of viruses, evensubtypes, tend to cause different severity
1.3 The situation of study on gastrointestinal bleeding in dengue patients in the world and Vietnam
Research conducted by ShubhankarMishra et al (2016) foundthat stomach bleeding accounted for 76.9% in pediatric patientsdiagnosed with severe dengue hemorrhagic fever According to BachVan Cam (2006), the proportion of pediatric patients withgastrointestinal bleeding is 45.1% Research conducted by HuynhNguyen Duy Liem (2010) shows that the proportion of pediatricpatients with gastrointestinal bleeding is 23.9%
Chapter 2: OBJECTIVES AND RESEARCH METHODS 2.1 Object, location and time of study
2.1.1 Research subjects
The study participants were 119 children diagnosed withDengue infection according to the Ministry of Health criteria in 2011and divided into two groups
Group of Dengue patients with GI bleeding: Including 59children, from 2 months to 15 years diagnosed with severe denguehemorrhage, inpatient treatment, and diagnosed with gastrointestinalbleeding
Group of Dengue patients without GI bleeding: Including 60patients from 2 months to 15 years old diagnosed with denguehemorrhage, inpatient treatment, without signs and symptoms of GIbleeding
Trang 10- Children aged less than 2 months.
2.1.2 Research time and location
The study was conducted at Nhi Dong 1 Hospital, Ho Chi Minh Citybetween 12/2014 – 12/2015
2.1.3 The process of selecting research subjects
When the patient is admitted to the hospital, select the patientfollowing the criteria for selection and exclusion criteria Monitorand record if there is GI bleeding, performing subclinical testsaccording to the study criteria, and recording At the same timechoose a case of dengue diagnosis following the criteria for selectionand exclusion criteria but without GI bleeding, which corresponds tothe age and gender included in the study sample, perform all testsaccording to the study criteria study, record in the medical record thegroup without GI bleeding
2.2 Research Methods
2.2.1 Research design
- Apply the cross-sectional descriptive research method
- All patients studied were thoroughly questioned and examined,performing tests, recording in the same medical record form (with theattached appendix)
2.2.2 Sample size and sampling methods
Conducting a cross-sectional descriptive study, we apply theformula of calculating the sample size for descriptive research to
Trang 11estimate a ratio We get the minimum sample size, large enough andreliable enough to be 58 Dengue patients In fact, we studied 59dengue patients with GI bleeding from 12/2014 to 12/2015 Inaddition, to be comparable, we also studied 60 patients diagnosedwith dengue hemorrhagic fever but without clinical manifestations of
GI bleeding
Regarding the sampling method, we use the whole sampling method
2.3 The content and research targets
The patient is carefully examined by the physical examination toidentify epidemiological factors, signs, and symptoms
- Research variables: Age, gender, duration of illness
- Clinical signs: pulse, fever, hemodynamic condition, skin, andmucous manifestations, GI bleeding manifestations both inside andoutside of the digestive tract Symptoms of another system such asrespiratory, neurological, musculoskeletal also record
- Subclinical criteria: full blood count; biochemical test; coagulationfunction test; using RT - PCR in virus identification
2.4 Processing and analyzing data
The data is processed by the method of medical statistics, using SPSSsoftware 13
2.5 Ethical issues in research:
Compliance with ethical regulations in research
2.6 Some limitations of the study
Subjects selected for the study were those of the regionalend-line hospital, so the pediatric patients were often worse thanthose at lower levels, private clinics or clinics or home treatmentsubjects Therefore, our study has not assessed all levels and clinicalsymptoms of subjects with Dengue virus concerning GI bleeding
Trang 12The number of patients selected is not large and the study time
is not long enough, so there is no comprehensive analysis of the virustype and the relationship with clinical manifestations and GI bleedingstatus
The ethics committee of Nhi Dong 1 Hospital does not approve GIendoscopy in pediatric patients with Dengue hemorrhagic fever, so
we do not perform gastrointestinal endoscopy for diagnosis (thediagnosis is only based on clinical and blood test)
Chapter 3: RESEARCH RESULTS
3.1 Clinical and subclinical characteristics of the gastrointestinal bleeding group
3.1.1 General characteristics of the group with gastrointestinal bleeding
Table 3.5 Distribution of gastrointestinal bleeding group by age group
Age group Quantity (n=59) Percentage (%)
Trang 133.1.2 Clinical characteristics of the group with gastrointestinal bleeding
Table 3.4 Clinical characteristics of gastrointestinal bleeding
symptoms (n = 59)
Gastrointestinal bleeding symptoms Quantity Percentage (%)
Table 3.4 shows that: among children with GI bleeding, thesymptoms of vomiting blood accounted for the highest rate (93.2%);followed by placement of gastric sonde with blood accounted for86.4% and symptoms of black stool defecation accounted for thelowest proportion (25.4%)
Table 3.5 Features of symptoms upon admission (n = 59)
Pain behind the eye orbit 1 1,7
Table 3.5 shows that: In particular, except for fever symptoms(98.1%), in the group with GI bleeding, there are 3 symptoms:
Trang 14abdominal pain (78.0%), languid (74.6%), fatigue (38.9%), the rate
of occurrence is higher than other symptoms
Table 3.6 Physical symptom characteristics on admission (n = 59)
Table 3.6 shows that common physical symptoms, when hospitalized in
GI bleeding group, include: respiratory failure (85.0%), pleural effusion(89.8%), circulatory failure (66.4%), vomiting (93.2%), hepatomegaly(81.4%), cold limb (79.7%), abdominal distention (78.0%)
Table 3.7 Bleeding outside digestive organs (n = 59)
Signs of bleeding Quantity Percentage (%)
Trang 153.1.2 Subclinical characteristics of the gastrointestinal bleeding group
Table 3.9 Hematological and coagulation test characteristics upon
admission
Red blood cells
Trang 16> 60 seconds 48 81,4
Table 3.9 shows: 72.8% of children with GI bleeding have increasederythrocyte upon admission In the group of pediatric patients withbleeding GI bleeding 65.5%, the number of white blood cellsdecreased 91.5% of subjects had GI bleeding with thrombocytopenia
At the time of the lowest platelet count, 100% of the patients in the GIbleeding group had values lower than normal 32.2% of pediatricpatients with hematocrit bleeding decreased 81.3% of pediatricpatients with GI bleeding had a PT rate < 60% 81.4% of pediatricpatients with GI bleeding had APTT > 60 seconds
3.2 Relationship between gastrointestinal bleeding with clinical, subclinical and viral symptoms in Dengue dengue patients
3.2.1 Clinical, subclinical characteristics and virus identification results of research subjects
Table 3.22 Distribution of dengue virus type due to gastrointestinal
bleeding
Assay
GI bleeding (n=60)
non-GI bleeding (n=59)
Total (n=119) p
Type 1 40 (66,7%) 13 (22,0%) 53
(44,5%)
< 0,01
(40,4%)Type 3 1 (1,7%) 2 (3,4%) 3 (2,5%)
(12,6%)