Effect of Fever Duration Before Hospitalization and Hemoconcentration to Length of Stay of Dengue Patients

Backgrounds: Early identification of clinical conditions and proper treatment to dengue patients is essential to prevent the development of more severe condition. This can lead to shorter length of stay and lower cost of patient care in hospitals. The objective of this study was to determine the effect of fever duration before hospitalization and hemoconcentration to length of stay of dengue patients. Methods: A cross-sectional study conducted by random sampling on the medical records of dengue patients hospitalized in RSPI Prof. Dr. Sulianti Saroso period January 2014-December 2015. Multivariate analyzes were performed with Cox regression. Results: There were 153 samples of dengue patient's medical record for analysis, 21.6% of them were hospitalized over 6 days. Duration of fever before hospitalization and hemoconcentration were significant to length of stay more than 6 days. Subjects with duration of fever for 3 days [aRR = 0.38; P = 0.024] and more than 3 days before hospitalization [aRR = 0.27; P = 0.000] were significant to length of stay more than 6 days. Subjects with hemoconcentration had higher risk by 1,8 times to length of stay more than 6 days [aRR = 1.84; P = 0.042]. Conclusion: Fever duration for 3 days, for more than 3 days before hospitalization, and hemoconcentration in dengue patients were significantly related to length of stay more than 6 days.


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The dengue infection is a disease caused by a virus carried by the mosquito Aedes aegypti which spreads rapidly, shifting from the urban areas to the rural areas. 1 The incidence rate of Dengue Hemorrhagic Fever (DHF) in Indonesia increased from 39. 8  Because of the variability of the length of hospital stay of dengue patients in RSPI-SS, so the hospital wants to know various factors that can affect the length of stay of patients with dengue. It is expected that understanding of the factors can improve the quality of service to patients with dengue and prevent the patients' condition from worsening. This study is conducted in order to identify the factors that affect length of stay of dengue patients in RSPI-SS. The research ethics are issued by the Committee for Health Research Ethics of RSPI-SS Number: 01/KE/I/2016.

METHODS
This study is a cross sectional study with retrospective analysis of the medical records of patients with dengue receiving inpatient care in RSPI-SS within the period of January 2014-December 2015. In total, there were 981 medical records of the patients diagnosed with dengue infection receiving inpatient care during the period from January 2014 to December 2015, then samples were selected using the randomize sampling method and 260 medical records were obtained (Lemeshow size). From this number, there were 107 medical records which have not inclusion criteria (did not have complete data), so the number of samples further analyzed were 153 medical records of patients with dengue.
The secondary data were collected using Case Report Form (CRF) consisting of In-Patient Data Form and Physical and Laboratory Examination Monitoring Form. The data collected covered the patients' age, sex, payment method, duration of fever before admission to the hospital, hemorrhage symptoms, the time the serological tests were performed, final diagnosis, hemoconcentration, thrombocytopenia, leukopenia, and the results of serological tests. The data on the results of IgG and IgM serological tests are grouped into the following: IgG(-)/IgM(-); IgG(-)/IgM(+); IgG(+)/IgM(-); IgG(+)/IgM(+). 5 An analysis was conducted to identify the dominant factor affecting the length of hospital stay of patients with dengue of more than 5 days. From the results of cross tabulation of the independent variable and the length of hospital stay variable, a prevalence of more than 10% was achieved. This study employed Cox regression analysis using the Stata software version 12. 6

RESULTS
The characteristics of 153 patients with dengue by their age and sex as shown in the medical records obtained can be seen in Figure 1. In Figure 1, it can be seen that the highest number of patients with dengue receiving inpatient care in RSPI-SS from January 2014 to December 2015 is found in the age group of 5-14 years, in which they are almost evenly distributed in the male and female sex groups. Analysis was continued on the length of stay of patients with dengue and the results can be seen in Table 1. Table 1 shows the distribution of patients with dengue with length of stay of more than 5 days and of 5 days or less, distributed by age, sex, and payment method when receiving inpatient care. The age grouping used in this study is the age groups of < Bivariate analysis was then conducted on the clinical and laboratory characteristics, and the results can be seen in Table 2.
In Table 2, it can be seen that variables of duration of fever of 3 days or more before admission to the hospital and hemoconcentration with a P value of < 0.25 are considered potential to be included as candidates in the multivariate analysis. Further, the multivariate analysis was conducted in three phases, namely the stepwise, enter and robust models, resulting in two factors remaining in the final model, namely the duration of fever of 3 days or more before admission to the hospital, and hemoconcentration. The results of the multivariate analysis can be seen in Table 3.

DISCUSSION
The study used secondary data derived from the medical records of patients who already had the results of IgG and IgM serological tests for DHF. The dependent variable is the length of hospital stay that is divided into two categories: 1) the length of hospital stay of 5 days or less and 2) the length of hospital stay of more than 5 days. The determination of the two categories was based on categories that used in previous studies 7 , which is not much different from the average length of hospital stay of dengue patients in RSPI Prof. Sulianti Saroso that is 5.3 days. There were 10 independent variables studied, and they were adjusted to the available data in the medical records.
Of the 153 subjects used in the study, it was found that 62 subjects (40.5%) experienced hemoconcentration, and they are distributed into two groups, i.e. 27 subjects (43.5%) with a length of hospital stay of 5 days or less, and 35 subjects (56.5%) with a length of hospital stay of more than 5 days. The data on hemoconcentration were obtained based on the percentage of the increase of the hematocrit level from the lowest one to the highest one recorded in the medical records of patients during the inpatient care. Based on DHF Control Guideline in Indonesia in 2013, the hemoconcentration condition for dengue fever is indicated by an increase of hematocrit level of more than 10% and dengue hemorrhagic fever of more than 20%.
The results of the study show that dengue patients who experienced hemoconcentration had a 1.8 times greater risk of a longer length of hospital stay of more than 5 days. Hemoconcentration conditions or increased hematocrit of more than 20% indicate the presence of plasma leakage due to increased capillary permeability. A decrease in body temperature accompanied by an increase in capillary permeability and plasma leakage indicates the onset of the critical phase of the disease, i.e. on the third to the sixth day of fever/illness. 1,8 This is consistent with the results of previous studies that showed an increase in hematocrit percentage of 23.79 % which provides the patients with DHF a risk of more than 2.5 times to experience shock than the percentage of the increase in hematocrit of 20.28%. 9 The laboratory parameters used for the diagnosis of DHF are the condition of thrombocytopenia and hemoconcentration or pleural effusion, ascites or hypoproteinemia. 8 10,11,12 Delay in the identification of hemoconcentration conditions and improper handling, especially in terms of fluid therapy when there is plasma leakage can lead to various complications such as advance pleural effusion, acute pulmonary congestion, and or cardiac failure and impaired electrolyte/metabolite. 1 Progression of the disease towards a more severe condition in dengue patients who experienced hemoconcentration causes the patients to have a longer length of hospital stay of more than 5 days.
In this study, the duration of fever for more than 3 days before hospitalization was protective variable which means not a risk factor for the patients' length of hospital stay of more five days [aRR=0.58; P=0.003]. The largest proportion (67.3%) was present in fever for more than 3 days and length of hospital stay for 5 days or less. Plausability biologic showed that the patients that hospitalized after had fever of more than 3 days (delayed hospitalization), did not have long treatment because of the patients have no complications such as hepatomegaly, gastrointestinal bleeding and acute kidney injury that can aggravate the condition of dengue patients. 13,14,15 In conclusion, hemoconcentration significantly related and had higher risk to length of stay more than 5 days in RSPI Prof. Dr. Sulianti Saroso. Consultation as early as possible at the health care facility will accelerate the identification of the dengue patient's clinical condition and reduce the risk of disease progression towards a severe dengue which do not require longer treatment. Longer treatment will result in a financial burden both for the patient and the hospital.