Use of Albumin levels as Warning Sign in Patients with Dengue with Warning Signs (Retrospective Observational Study)

INTRODUCTION: A decrease in serum albumin levels in a dengue patient is correlated with higher likelihood of an adverse outcome. The levels can be utilized as an early predictor of likelihood of clinical worsening, despite adequate treatment. OBJECTIVES: A retrospective observational study to analyze initial serum albumin levels in admitted patients with dengue with warning signs and its correlation with outcome. MATERIALS AND METHODS: Over a 5-month period from August 2021, 147 adult patients (age >14 years) who had dengue with warning signs (as per WHO classification) on admission to Medical Intensive Care Unit, Fortis Hospital, Mohali, Punjab (India) were retrospectively evaluated. Admitted cases of dengue fever were divided into three groups based on serum albumin levels on presentation: mild (>3.5 mg/dL), moderate (2.5 – 3.5 mg/dL), and severe (< 2.5 mg/dL). Initial serum albumin was co-related with survival or non – survival. Clinical, hematological, and biochemical parameters, as recommended in the WHO guidelines were used to look for correlation with predictive of severity, were compared between those who showed clinical worsening and developed TSFA and multi organ failure. All patients were managed according to the WHO and MoHFW guidelines for the management of adult dengue, published by the Ministry of Health, India. RESULTS: Out of the 147 patients. 13 patients (8.8%) had severe hypoalbuminemia (< 2.5 mg/dL), 48 patients (32.65%) had moderate hypoalbuminemia (2.5 – 3.5 mg/dL), and 46 (31.29%) had normal albumin levels (> 3.5mg/dL). Mortality was noted to be highest in patients who presented with severe hypoalbuminemia (38.4%) as compared to other two groups where the mortality was 14.58% and 0%. DISCUSSIONS: Dengue remains to be a disease of concern due to untoward high morbidity and mortality among young population. WHO reported over 8 times increase in number of cases over last two decades with increase in more than four times the mortality from 2010 to 2019. The actual number might be higher as only severe cases of dengue are hospitalized and many of the mild dengue cases go unreported. 1 Dengue Virus infected cells release inflammatory mediators and form immune complexes. This results in a complement cascade, thus in increased permeability and haemorrhagic manifestations. Plasma leakage that leads to shock or fluid accumulation, sufficient to cause respiratory distress, is defined as “Clinically Significant” by the WHO. Reactive oxygen species, enzymes, and pro-inflammatory molecules (e.g. TNF-α, IL-6, IL-8 and IFN-γ) breaks down the endothelial glycocalyx layer transiently, thus allowing plasma to reach the underlying intercellular junctions and leak out of the blood vessel. Albumin and other smaller proteins is lost from the blood vessels, resulting in hypoalbuminemia and third space loss.27. All cases of severe dengue need institutional care and monitoring, but since there and no definite tools for the diagnosis or for prognostication of dengue cases, over admission of patients is common. 13 Most of the studies to differentiate severe from mild dengue have been conducted in paediatric age group.3 These studies showed that it was difficult to differentiate mild from severe dengue until the critical phase developed.13,26. Attempts have been made to assess the severity of dengue by developing scores, use predictors live PCV (packed cell volume), use clinical signs (pulse volume, narrow pulse pressure (< 20 mmHg), hypotension, shock, etc.). Out of these, presence of third space fluid accumulation is considered the most objective evidence for plasma leakage.1,26. The baseline value of haematological parameters are rarely available, and the presence of anaemia, haemorrhage, and fluid resuscitation often makes the interpretation of the haematological parameters difficult.1 In our study, the serum albumin levels were observed and correlation with clinical symptoms and mortality in hospital was studied. Among patients who had poor outcome or developed the complication after admission, a fall in serum albumin levels were noted and of those in whom serum albumin levels remained to be low despite correction went on to develop third space fluid accumulation and multi organ failure and tend to have worse outcomes. Third space fluid accumulation, pleural effusions and ascites were the common ultrasonographic sign of plasma leakage.14 As serum albumin levels were lower in patients who developed third space fluid accumulation and those who did not, the complication seems to be primarily a result of increased capillary permeability during the disease process. Our study had its own limitations. Firstly, it was a retrospective study with its inherent bias associated. Secondly, the number of patients were small compared to the large numbers of cases across the country. Thirdly, this was a study done in a single ICU. More studies will be required to be done in a controlled environment to authenticate and validate the data derived by us.