P - ISSN : 2349-6592    |    E - ISSN : 2455-7099
Year : 2016 | Volume : 3 | Issue : 4 | Page : :20-24
Source of Funding:None Conflict of Interest:None
Background:India is among the countries reporting regular outbreaks of Dengue infection. Present study describes clinical profile and outcome of severe dengue cases.
Methods:It is a retrospective observational study. All dengue patients admitted in PICU, from June 2015 to December 2015 were classified as per new WHO-2009 classification, and only those with severe dengue were included in the study. Clinical features, laboratory parameters and final outcome were studied and described.
Results:Fever, pain abdomen and vomiting were found to be most common presenting symptoms. Thrombocytopenia was found in 100% cases and leukopenia in 20% cases. Shock was present in all the patients and average time taken for shock reversal was 2.4 days. Hepatitis (68.5%), AKI (54%) and encephalitis (14.2%) were the main complications. Survival rate was 91.4%.
Conclusion:renal and CNS involvement is more common in dengue then previously reported. Use of inotropes and mechanical ventilation are associated with higher mortality.
Key words:severe dengue, shock, thrombocytopenia, PELOD score.
Dengue is one of the most rapidly spreading mosquito born viral disease in the world. Dengue has a wide spectrum of clinical presentation, often with unpredictable clinical evolution and outcome1. Most patients have a self-limiting non-severe clinical course, and a small proportion progress to severe disease, mostly characterized by plasma leakage with or without hemorrhage. The aim of current study was to observe the clinical profile, complications and final outcome in patients of severe dengue (as per WHO classifications).2
Material and Methods:
This study was conducted in Pediatric intensive care unit (PICU), at Kalawati Saran Children’s Hospital and Lady Hardinge Medical college, New Delhi. All admitted patients from age 1 month to 18 years were considered for inclusion, during dengue outbreak from June – December 2015. Critically sick children with severe dengue (as per WHO, 2009) 2 not responding to initial therapy or worsened after initial response within 48 hours of hospitalization were included in the study. Seropositive cases transferred from general ward to PICU after 48 hours of hospitalization were excluded. Children who were managed in other hospitals before being referred to our center were also excluded. PELOD score3 was calculated at the time of admission in PICU. The patient was considered to have shock if the pulse pressure (i.e. the difference between the systolic and diastolic pressures) is ≤ 20 mm Hg or he/she has signs of poor capillary perfusion (cold extremities, delayed capillary refill, or rapid pulse rate).2 Children who had co-infection with malaria, typhoid, or scrub typhus were compared with other children. Detailed clinical examination along with laboratory parameters like serial hemogram, renal and liver function tests, serum electrolytes, chest X ray, abdominal sonography and serological tests for dengue (IgM and IgG antibody) and NS1 antigen were done as per PICU treatment protocol. Peripheral smear for malaria, malaria antigen test, widal test, blood culture, weil felix test were also sent wherever indicated clinically. Either death or discharge was recorded as final outcome. Descriptive statistics were calculated and children with and without co-infection were compared using independent sample t test. Statistical analysis was done using SPSS version 20.
A total of 198 cases of probable dengue were admitted to PICU from June 2015 to December 2015, of them 156 were seropositive and only 35 patients satisfied the inclusion criteria and were enrolled. Male to female ratio was 1.3:1. Most patients presented in age group 5-10 years, and only one case of infantile dengue was included in study (Table 1).
Fever, pain abdomen and vomiting were the main presenting complaints in most of the patients and with fever being the most common symptom. Other manifestations include rashes, altered sensorium, edema, fast breathing and bleeding manifestations (Figure 1).
On clinical examination, features of shock were present in 33 patients at the time of admission while 2 more patients developed shock during their stay in PICU. Tachycardia was present in 33 patients at admission, while hypotension was present in 25 patients (71.4%) at admission. Mean PELOD score was determined as 21.6 in all included patients. Mean heart rate, respiratory rate, and systolic blood pressures of all the included patients are shown in Table 1. On clinical examination, features of shock were present in 33 patients at the time of admission while 2 more patients developed shock during their stay in PICU. Tachycardia was present in 33 patients at admission, while hypotension was present in 25 patients (71.4%) at admission. Mean PELOD score was determined as 21.6 in all included patients. Mean heart rate, respiratory rate, and systolic blood pressures of all the included patients are shown in Table 1. Routine blood investigations like complete hemogram, LFTs and KFTs were done for all patients as per PICU protocol. Thrombocytopenia, at admission, was present in most (88.5%) of the patients, and nearly two third patients (68.5%) had deranged LFTs. Blood urea and serum creatinine level were found to be elevated in 54% of patients. Peritoneal dialysis was done in 3 of these patients. Only two patients had coagulopathy in form of deranged INR at presentation (Table 2).
In our study, liver (68.5%) and kidney (54.2%) were most severely affected organs, and 80% patient developed pleural effusion. Dengue encephalitis was found in 14.2% patients. Co infections were present in 6 patients, and one of them expired. Malaria was present in 2 patients, while scrub typhus, ASOM, liver abscess and acinetobacter sepsis was present in other four patients. A comparison of various features in patients with and without co infection is shown in Table 3.
Most of the patients (94.2%) had features suggestive of shock at the time of admission in PICU, and 85.7% patients had signs of ongoing fluid leak. Average time taken for shock reversal was 2.4 days. During the recovery phase, 13 patients developed features of fluid overload. Onset and duration of fluid leak, shock and thrombocytopenia in relation to fever has been shown in Figure 2.
Initially all patients were managed as per WHO protocol for severe dengue, but further fluid therapy in PICU was guided by IVC (inferior vena cava) collapsibility as seen on trans-abdominal ultrasonography. IVC collapsibility of >50% was taken as a marker for fluid responsiveness and more fluid was administered to all such patients. Platelets transfusion was given only in cases with severe bleeding manifestations. Patients with catecholamine refractory shock were considered for elective mechanical ventilation. Inotropes were administered to 26 patients (74.2%), and 13 (37.1%) patients received blood transfusion. Mechanical ventilation was used in 9 (25.7%) patients. A total of 3 (8.6%) patients died out of 35 cases of severe dengue. All 3 patients who died had catecholamine refractory shock and were mechanically ventilated.
Total 35 cases of seropositive, severe dengue patients were admitted in PICU, Kalawati Saran Children Hospital during the study period and their clinical features, complications, laboratory parameters and final outcome has been described. Male: female ratio was found to be 1.3:1, which is comparable to other studies as described by agarwal et al4 with a ratio of 1.4:1, and Rasul CH et al5 with a ratio of 1.21:1. Commonest age group in present study was 5-10 years. Rahul CH et al showed a similar finding with common age group of 5-9 years, whereas a study by Gomber et al6 showed the commonest age group being 6-15 years. With regards to clinical features, fever was the most common presenting feature and was present in 100% of the cases. Studies by Sajid et al7 and Misra et al8 also reported fever in 100% cases whereas Aggarwal et al4 reported fever in 93% cases. Pain abdomen was found to be the second most common symptom, being present in 85.7% cases, followed by vomiting which was present in 74.2% cases. A recent study by Bhave et al9 showed similar findings with abdominal pain and vomiting described as most common presenting features. However the previous studies reported abdominal pain as a less common symptom as shown by agarwal et al4 (49%), and Kale et al10 (54%). This discrepancy in symptomatology may be due to the fact that abdominal pain is seen more commonly in patients with shock, and our study enrolled only severe dengue patients and most of them had shock at presentation. In the present study thrombocytopenia (platelets <1, 00,000/dL) was found in 88.5% patients at admission, although 100% patients developed thrombocytopenia at some time during hospital stay. Leukopenia was present in 20% patients. Agarwal et al 4 reported thrombocytopenia in 100% cases while leukopenia in 15% cases, while Bhave et al9 reported thrombocytopenia in 95.3% cases. Average duration of thrombocytopenia was found to be 7 days. Severe dengue is usually associated with multi organ involvement and complications caused by it. In our study liver was found to be most commonly affected organ followed by kidney. We found hepatitis in 68.5% cases while AKI in 54% cases. While liver involvement has been reported earlier as predominant organ involvement in dengue, interestingly very few studies have reported the incidence of AKI in dengue. 11-13Khalil et al13 reported an incidence of AKI in 13.3% cases, while Laoprasopwattana et al.11 have reported an incidence of only 0.9% in Thai children. Mehra et al12 have reported an incidence of 10.8% of AKI in dengue. Even the studies done in ICU set up have shown a very low incidence of AKI in dengue patients. In a Brazilian intensive care unit for infectious diseases, dengue was the cause of 4% of the cases of AKI diagnosed using the RIFLE criteria14. Low incidence of AKI in previous studies may be due to the different definitions used to define AKI. We used acute kidney injury network criteria to define AKI in our patients.12
In our study encephalitis was found in 14.2% cases, which is again higher then what is reported in previous studies. Kale et al10 reported encephalitis in 6% cases, while both Agarwal et al4 and Tripathi et al15 reported it in only 4% cases. The higher incidence of both AKI and encephalitis in our study can be due to the fact that our study was conducted in PICU and only sickest of the cases were admitted. In a tropical country like India, it is not unusual to find many infections at same time in a single patient, especially during an epidemic. We also found co-infections like malaria (2), scrub typhus (1), liver abscess (1), ASOM (1) and bacterial sepsis (1) in our patients. The duration of fever, duration of hospital stay, average duration of both leukopenia and thrombocytopenia, recovery period for shock and mortality was higher in those with co-infections. Mortality was found to be 6.8% in severe dengue without co-infection, while it was 16.6% in those with co-infection. Co infections in dengue have been poorly studied, and more so in pediatric age group. However, malaria as a co infection has been described in few studies16,17 and a retrospective study16 showed that morbidity and mortality was higher in those with dengue and malaria co infection.
We used mechanical ventilation in 9 of our patients with refractory shock, and 3 of these patient died (33.3%). Very few studies have described the role of mechanical ventilation in management of severe dengue cases. A study from Sri Lanka by Chulananda et al18 found mechanical ventilation to be associated with significantly higher mortality rate of 79% as compared to those who did not require mechanical ventilation (2.8%). Inotropes were administered in 74.2% cases, and were also associated with higher mortality rates (11.5%). Chulananda et al18 reported a mortality of 55.5% patient who received inotropes. Transfusion of blood products was also associated with higher death rates of 23.3%.
What was new in this outbreak??
According to National Vector Borne Disease Control Program (NVBDCP) data19, current outbreak of dengue was one of the worst in last 20 years. In 2015 dengue outbreak, 15836 dengue cases were reported from Delhi, which leads to 46 deaths (0.29%). Although total number of dengue cases increased tremendously in this outbreak, the mortality rate has not been changed by much. This may be because of that better understanding of disease pathophysiology now, and newer guidelines for fluid management in dengue.2
This study was conducted to look at the critical care aspect of severe dengue. We only enrolled the critically sick patients of dengue, as indicated by their high PELOD score, and analyzed their course during hospital stay, associated complications, response to treatment and final outcome. Our study indicates that patients of severe dengue who are admitted in PICU have higher incidence of complications. AKI and encephalitis are more common then previously reported by various studies. Early institution of mechanical ventilation in cases of catecholamine refractory shock had shown more favorable outcome then previously reported, however larger observational studies are required to say it conclusively. Our study has its limitation due to small sample size but it provides useful information for managing the most severe cases of dengue. Continuous monitoring, early detection of AKI, timely use of mechanical ventilation, and fluid therapy guided by IVC collapsibility can all be used successfully to improve the final outcome in severe dengue patients.
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