Clinical Profile and Outcome of Dengue Fever in Multidisciplinary Intensive Care Unit of a Tertiary Level Hospital in India

ABSTRACT Background India is one of the seven identified countries in South-East Asia region regularly reporting dengue fever (DF)/dengue hemorrhagic fever (DHF) outbreaks. Even though the dengue prodrome and evolution of illness are most often similar in many patients, progress and outcome may differ significantly depending on the severity of illness as well as treatment instituted. We studied the clinical manifestations, outcome and factors predicting mortality of serology confirmed dengue fever cases admitted in Multidisciplinary Intensive Care Unit (MICU) of a high acuity healthcare facility in India. Methodology All patients with serology proven dengue fever admitted to MICU between 1st July 2015 and1st December 2015 were included in the study. Clinical presentation, laboratory findings, severity of illness scores and outcome were recorded. Results Majority of the patients (58.4%) belonged to 21–40 year age group. Hepatic (96.8%) followed by hematological (79.2%) involvement were the most common findings. CNS involvement observed among 27%. Survival to hospital discharge was 78.9%. Respiratory and gastrointestinal system involvement was associated with increased mortality. Acute respiratory distress syndrome (ARDS), acute kidney injury (AKI) and shock were the clinical syndromes associated with mortality. Serum lactate, aspartate transaminase (AST) and alanine transaminase (ALT) were significantly elevated among non survivors. Significant difference in sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation (APACHE) scores was also observed among survivors and non survivors. Conclusion Organ system involvement and higher disease severity scores are strong predictors of mortality. High index of suspicion for atypical manifestations of dengue is warranted. How to cite this article Padyana M, Karanth S, Vaidya S, Gopaldas JA. Clinical Profile and Outcome of Dengue Fever in Multidisciplinary Intensive Care Unit of a Tertiary Level Hospital in India. Indian J Crit Care Med 2019;23(6):270–273.


IntroductIon
Dengue is a vector born tropical viral fever spread by Aedes egypti and Aedes albopticus mosquitoes.Incidence of dengue is rising in India from 6.34 per million population between 1998 and 2009 to 34.81 per million population between 2010 and 2014. 1 Presentation of dengue fever can vary from malaise, fatigability as a part viral prodrome to shock and multiorgan dysfunction syndrome as a part of severe illness. 2 Outcomes of patients with dengue fever admitted to critical care units have been studied less often.Prognostic factors which determine the clinical outcome of critically ill patients with dengue fever remain unclear. 3

Methodology
Retrospective single center study which included patients admitted to MICU with serology proven 4 dengue fever with warning signs and severe dengue between 1st July and 1st December 2015 NS1-Antigen Strip® ELISA (BioRad), IgM and IgG-Capture ELISA Panbio® (Alere TM ) were used for dengue serology testing.Patient management was as per WHO, Surviving Sepsis Campaign guidelines and established standards in intensive care practice.Demographics including age and gender distribution, signs and symptoms, SOFA and APACHE II scores were recorded.Outcome details including organ involvement and survival to hospital discharge were recorded.Statistical Analysis done using SPSS version 13.0 used for data analysis.Data analyzed by frequency, percentage, mean (±SD)/ Median (Inter Quartile Range-IQR).Logistic regression analysis for determination of factors predicting mortality.
Predominant organ involvement was hepatic (transaminitis, jaundice) followed by gastrointestinal (abdominal pain, distension, loose stools, vomiting, ascitis) systems.Forty-four percent patients had gallbladder wall edema on ultrasound evaluation.Hematological involvement was predominantly thrombocytopenia and raised hematocrit.Respiratory system involvement had ARDS and pleural effusion.CNS manifestations included intracranial bleed, cerebral infarction and cerebellitis (in one patient).Patients with refractory shock requiring vasopressor initiation were 30.2% (Fig. 1).An average of 2 units of single donor platelet transfusion requirement per patient was noted in our study (Table 3).
Secondary sepsis was noted in 16.5% of patients.Half of these were blood stream infections.Predominant organisms responsible are gram-negative (Klebsiella pneumoniae and Acenetobacter baumanii).Ten (13.1%) patients required tracheostomy for liberation of mechanical ventilation due to ICU acquired weakness (5.2%) and persistent neurological abnormalities like hemiparesis, ataxia, dysarthria, etc.

dIscussIon
Our study looked into epidemiological factors, organ involvement and mortality during ICU stay.
In our study, we noted that 50 patients (52.1%) had dengue with warning signs and 41 patients (42.7%) had severe dengue and only 5 patients (5.2%) had dengue without warning signs based on WHO classification. 4We observed that the mean age of our cohort of patients was 37 years.ICU requirement was significantly high among age group of 21-40 (58.4%).Similarly, in a study by Juneja et al. 39.6 year was the mean age of patients requiring ICU admission with dengue fever suggesting that younger age group is at higher risk compared to older. 5Vomiting, abdominal pain and bleeding manifestations were common warning signs which warranted ICU transfer, similar to observations in previous studies. 3,6ultiorgan involvement in dengue is well known.In our study we observed Hepatic involvement among 96.8%.AST and ALT were significantly high among non survivors.Similarly in a study by Nayak et al liver involvement was noted among 97.33%,AST and ALT were significantly high among dengue hemorrhagic fever and dengue shock syndrome group. 7espiratory and gastrointestinal involvements had increased risk of mortality.AKI and moderate to severe ARDS (with PF ratio <200) was significantly high among non survivors.Similarly Shock and Lactates were also noted to be significantly high among non survivors.Study by Thanachartwet et al showed significantly high lactates among patients with organ failure and shock. 8In a study by Chen et al moderate ARDS (PF Ratio <200) followed by shock (SBP <90 mm Hg or MAP <65) and multiorgan failure was significant among non survivors. 3A study by Jain et al. had described liver and renal involvement, ARDS, Shock requiring vasopressor, metabolic acidosis as predictors of mortality. 9A study done in Cuttack, India had showed predominant organ failure was coagulation (48%).
Respiratory failure was 19% and cardiovascular failure was 8%. 10 Neurological involvement may occur without associated bleeding manifestations, rash or thrombocytopenia.Neurological complications are reported to be rare in dengue as it is a nonneurotropic virus. 11However we observed that many patients (27.1%) were presented with altered sensorium as initial manifestation either due to primary CNS involvement (encephalopathy, encephalitis or intracranial bleed) or secondary to profound shock.Karoli et al described neurological involvement upto 14% in patients with dengue fever in the form of encephalopathy, hypokalemic periodic paralysis, myositis and Gullain-Barre syndrome.Another study by Nimmagadda et al placed incidence of neurological manifestations at 2% encephalitis or meningitis. 12,13In our study, three patients had infarct, two sustained intracranial hemorrhage, one had Posterior Reversible Encephalopathy Syndrome (PRES) and other was found to have cerebral abscess with hydrocephalus (overall incidence 8.3%).One of the patients with multiple infarcts had cerebrospinal fluid polymerase chain reaction (PCR) positive for dengue.Recently published data from Taiwan demonstrated that altered sensorium is an independent risk factor for mortality. 14owever in our study, we did not find any significant association between altered sensorium and mortality.
Moratlity has been shown to be high among age group of >60 years in prior studies. 3Our study had younger patients between 21 years and 40 years requiring ICU and mortality was noted to be high among females between the age group of 21-40 years.In a retrospective cohort study from Brazil mortality of severe dengue was noted to be 3.1% over a period of 14 years.Age >55 year was associated with increased mortality. 15In a Chinese study, female sex and age group 30-39 years was associated with increased risk of dengue hemorrhagic fever and mortality especially with dengue 2 serotype 6 Pang et al noted that adult patients belonging to 50 to 59 year age group or patients with diabetes had 5 times increased risk for ICU admission and increased mortality compared to patients who are younger than 30 year and without diabetes. 16Another study done in Singapore between 2007 and 2008 during dengue sero-type 2 epidemic observed that female sex, age group 30-49 years and presence of diabetes or hypertension were associated with increased risk of dengue hemorrhagic fever. 17However in our study, diabeties was not associated with significant increase in mortality.
There are certain limitations in our study.Interpretation of this study should be done bearing in mind that it is a retrospective single center study involving patients admitted in the intensive care unit.However, this study sheds light onto the factors which could predict mortality among patients admitted with dengue to critical care unit.conclusIon Lactatemia, transaminitis, higher disease severity scores (APACHE II and SOFA), Shock, AKI and PaO 2 /FiO 2 ratio less than 200 were associated with increased mortality.We advise high index of suspicion for atypical CNS manifestations in patients admitted with dengue fever to intensive care unit.

Table 2 :
Clinical features

Table 4 :
Mortality Fig. 1: Organ involvement in patients during dengue fever

Table 5 :
Factors associated with mortality

Table 6 :
Evaluation of variables in survivors and non survivors