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Clinical profile, intensive care unit course, and outcome of patients admitted in intensive care unit with dengue Deven Juneja DNB, FNB , Prashant Nasa MD, FNB, Omender Singh MD, FCCM, Yash Javeri DA, IDCC, Bhupesh Uniyal DA, IDCC, Rohit Dang MPharm Department of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi-110017, India Keywords: Dengue infection; Epidemiology; Intensive care Abstract Purpose: The purpose of the study was to assess the clinical profile and course of dengue patients admitted to the intensive care unit (ICU) and to identify factors related to poor outcome. Methods: All patients with dengue admitted to ICU over 2.5 years were included prospectively. Severity of illness was assessed by the Acute Physiology and Chronic Health Evaluation (APACHE) II score, and organ failure was determined by the Sequential Organ Failure Assessment score. Primary outcome measure was 28-day mortality. Logistic regression analysis was performed to identify factors predicting mortality. Results: Data from 198 patients were analyzed. Mean age was 39.56 ± 17.1 years, and 61.1% were male. The commonest complaints were fever (96%) and rash (37.9%). Mean admission APACHE II and Sequential Organ Failure Assessment scores were 7.52 ± 7.8 and 4.52 ± 3.4, respectively. The commonest organ failure was coagulation (43.4%) followed by respiratory failure (13.1%). Vasopressors were required by 11.6%; and dialysis and mechanical ventilation were required by 7.6% and 9.1%, respectively. Mortality was 12 (6.1%); and on multivariate analysis, APACHE II score (odds ratio, 1.781; 95% confidence interval, 0.967-3.281; P = .048) could independently predict mortality. Conclusions: Patients with dengue fever may require ICU admission for organ failure. Outcome is good if appropriate aggressive care and organ support are instituted. Admission APACHE II score may predict patients at higher risk of death. © 2011 Elsevier Inc. All rights reserved. 1. Introduction The World Health Organization (WHO) has identified dengue as the most rapidly spreading mosquito-borne viral disease in the world. It is estimated that 50 million dengue infections occur every year and that around 2.5 billion of the world's population lives in dengue-endemic countries [1]. Nearly 75% of the current global disease burden due to dengue is borne by the people living in the Southeast Asia region and Western Pacific region [1]. It is a major health issue in tropical and subtropical countries like India, and there have been annual dengue outbreaks in northern India especially in the postmonsoon season. Dengue fever may present with a wide spectrum of nonspecific clinical symptoms and may have unpredictable clinical course and outcome. It may present as dengue fever, dengue haemor- rhagic fever, or dengue shock syndrome [2]. Although most Corresponding author. Tel.: +91 9818290380. E-mail address: [email protected] (D. Juneja). 0883-9441/$ see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jcrc.2011.05.007 Journal of Critical Care (2011) 26, 449452

Clinical profile, intensive care unit course, and outcome of patients admitted in intensive care unit with dengue

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Page 1: Clinical profile, intensive care unit course, and outcome of patients admitted in intensive care unit with dengue

Journal of Critical Care (2011) 26, 449–452

Clinical profile, intensive care unit course, and outcomeof patients admitted in intensive care unit with dengueDeven Juneja DNB, FNB⁎, Prashant Nasa MD, FNB, Omender Singh MD, FCCM,Yash Javeri DA, IDCC, Bhupesh Uniyal DA, IDCC, Rohit Dang MPharm

Department of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi-110017, India

0d

Keywords:Dengue infection;Epidemiology;Intensive care

AbstractPurpose: The purpose of the study was to assess the clinical profile and course of dengue patientsadmitted to the intensive care unit (ICU) and to identify factors related to poor outcome.Methods: All patients with dengue admitted to ICU over 2.5 years were included prospectively. Severityof illness was assessed by the Acute Physiology and Chronic Health Evaluation (APACHE) IIscore, and organ failure was determined by the Sequential Organ Failure Assessment score. Primaryoutcome measure was 28-day mortality. Logistic regression analysis was performed to identify factorspredicting mortality.Results: Data from 198 patients were analyzed. Mean age was 39.56 ± 17.1 years, and 61.1% were male.The commonest complaints were fever (96%) and rash (37.9%). Mean admission APACHE II andSequential Organ Failure Assessment scores were 7.52 ± 7.8 and 4.52 ± 3.4, respectively. The commonestorgan failure was coagulation (43.4%) followed by respiratory failure (13.1%). Vasopressors wererequired by 11.6%; and dialysis and mechanical ventilation were required by 7.6% and 9.1%, respectively.Mortality was 12 (6.1%); and on multivariate analysis, APACHE II score (odds ratio, 1.781; 95%confidence interval, 0.967-3.281; P = .048) could independently predict mortality.Conclusions: Patients with dengue fever may require ICU admission for organ failure. Outcome is goodif appropriate aggressive care and organ support are instituted. Admission APACHE II score may predictpatients at higher risk of death.© 2011 Elsevier Inc. All rights reserved.

1. Introduction

The World Health Organization (WHO) has identifieddengue as the most rapidly spreading mosquito-borne viraldisease in the world. It is estimated that 50 million dengueinfections occur every year and that around 2.5 billion of theworld's population lives in dengue-endemic countries [1].

⁎ Corresponding author. Tel.: +91 9818290380.E-mail address: [email protected] (D. Juneja).

883-9441/$ – see front matter © 2011 Elsevier Inc. All rights reserved.oi:10.1016/j.jcrc.2011.05.007

Nearly 75% of the current global disease burden due todengue is borne by the people living in the Southeast Asiaregion and Western Pacific region [1]. It is a major healthissue in tropical and subtropical countries like India, andthere have been annual dengue outbreaks in northern Indiaespecially in the postmonsoon season. Dengue fever maypresent with a wide spectrum of nonspecific clinicalsymptoms and may have unpredictable clinical course andoutcome. It may present as dengue fever, dengue haemor-rhagic fever, or dengue shock syndrome [2]. Although most

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450 D. Juneja et al.

patients recover after a self-limiting mild disease, a smallproportion progress to severe dengue infection. Withoutappropriate therapy, dengue haemorrhagic fever may have ahigh fatality rate exceeding 20% [3]. But with early aggres-sive care, death rates can be reduced to less than 1%; andtherefore, patients with severe disease may require intensivecare [3]. However, there is a dearth of data regarding theepidemiology, clinical course, and outcome of patients withdengue fever admitted to intensive care units (ICUs). Hence,we undertook this study to assess the clinical profile and ICUcourse of dengue patients admitted to ICU and to identify thefactors related to poor outcome.

Table 1 Comparison between the baseline characteristics ofsurvivors and nonsurvivors

Parameterof interest

Overall(n = 198)

Survivors(n = 186)

Nonsurvivors(n = 12)

Pvalue

Age, y 39.56 ± 17.1 39.25 ± 16.9 44.33 ± 19.9 .320Sex .769Male 121 (61.1%) 113 (60.8%) 8 (66.7%)Female 77 (38.9%) 73 (39.2%) 4 (33.3%)APACHE IIscore

7.52 ± 7.8 6.05 ± 5.2 30.25 ± 5.8 .000 ⁎

Predicteddeath rate

12.31 ± 17.3 8.65 ± 8.8 68.97 ± 17.1 .000 ⁎

SOFA score 4.52 ± 3.4 3.95 ± 2.5 13.42 ± 3.1 .000 ⁎

Respiratoryfailure

26 (13.1%) 15 (8.1%) 11 (91.7%) .000 ⁎

Coagulationfailure

86 (43.4%) 80 (43%) 6 (50%) .766

Cardiovascularfailure

20 (10.1%) 10 (5.4%) 10 (83.3%) .000 ⁎

Neurologyfailure

5 (2.5%) 1 (0.5%) 4 (33.3%) .000 ⁎

Hepatobiliaryfailure

12 (6.1%) 12 (3.2%) 0 (0%) .364

Renal failure 7 (3.5%) 5 (2.7%) 2 (16.7%) .060Vasopressorsupport

23 (11.6%) 11 (5.9%) 12 (100%) .000 ⁎

Renalreplacementtherapy

15 (7.6%) 5 (2.7%) 10 (83.3%) .000 ⁎

Mechanicalventilation

18 (9.1%) 6 (3.2%) 12 (100%) .000 ⁎

ICU stay, d 3.07 ± 1.8 3.12 ± 1.8 2.25 ± 1 .103

⁎ P value b .05 was considered significant.

2. Methods

A prospective observational cohort study was conductedin a medical ICU of a tertiary care center located in themetropolitan city of New Delhi, India. All consecutive adultpatients with dengue infection admitted to ICU during thestudy period of July 2008 to December 2010 were includedprospectively. Diagnosis of dengue infection was made onthe basis of a positive nonstructural protein 1 antigen(enzyme-linked immunosorbent assay) result or the presenceof serum immunoglobulin M antibodies (enzyme-linkedimmunosorbent assay) [3]. Data were collected regarding thebaseline patient characteristics, need for organ support, andoverall ICU outcome. Severity of illness was assessed bythe Acute Physiology and Chronic Health Evaluation(APACHE) II score [4], and presence of organ failure wasdefined by admission Sequential Organ Failure Assessment(SOFA) score [5] of more than 2 for that organ system.Patients were followed up to 28 days after ICU discharge.Primary outcome measure was 28-day mortality. Individualorgan components of SOFA score were also compared withAPACHE score and total SOFA score by using area underthe receiver operating characteristic (AUROC) curve todetermine which organ system better differentiates betweensurvivors and nonsurvivors. Nonsurvivors were defined asthose who died during their ICU stay or within 28 days ofICU discharge.

Patients were managed as per the WHO guidelines [3].Blood and platelet transfusions were given only in cases withsuspected or severe bleeding. Platelets were transfused onlywhen the platelet counts were less than 20 000/mm3 or inpatients with platelet count greater than 20 000/mm3 withactive bleeding or undergoing any invasive procedure [6].Single-donor platelet concentrate was preferably given,when available.

2.1. Statistical analysis

We used SPSS version 14.0 (SPSS Inc, Chicago, IL) forthe statistical analysis. The means of continuous variableswere compared using Student t test, and the categoricalvariables were compared using χ2 test or Fisher exact test as

appropriate. Statistical significance was set at a 2-sidedP value b .05. Univariate and multivariate logistic regressionanalyses were performed to assess factors predicting mortality.

3. Results

Out of a total of 2052 admissions during the study period,data from 198 (9.65%) patients with dengue fever wereanalyzed. Mean age was 39.56 ± 17.1 years, and 121 (61.1%)were males (Table 1). The commonest presenting com-plaints were fever and rash, which were present in 190 (96%)and 75 (37.9%) patients, respectively. The commonestreason for ICU admission was severe thrombocytopenia(b20 000/mm3) with or without minor bleeding manifesta-tions like petechiae, subconjunctival hemorrhages, hematu-ria, or melena in 71 patients. Other reasons for ICUadmission included systemic inflammatory response syn-drome or severe sepsis in 42, severe bleeding in 23, respi-ratory distress in 22, hepatitis or jaundice in 10, alteredsensorium in 9, shock in 8, severe abdominal pain in 4,

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451Clinical profile, course, and outcome of dengue patients

severe dehydration in 4, reduced urine output in 3, andpersistent vomiting in 2 patients. Mean admission APACHEII and SOFA scores were 7.52 ± 7.8 and 4.52 ± 3.4, respec-tively. The commonest organ failure was coagulation(43.4%) followed by respiratory (13.1%) and cardiovas-cular failure (10.1%). Vasopressor support was required by11.6%; and renal replacement and mechanical ventilationwere required by 7.6% and 9.1%, respectively. The meanICU length of stay was 3.56 ± 2.1 days. As all deathsoccurred during the ICU stay, ICU and 28-day mortalitywas 12 (6.1%).

On univariate analysis, admission APACHE II and SOFAscores; presence of respiratory, cardiovascular, and neuro-logical failure; and need for vasopressor, renal, and mechani-cal ventilator support were found to be associated withincreased mortality (Table 1). However, when these factorswere analyzed in a multivariate analysis, only admissionAPACHE II score (odds ratio, 1.781; 95% confidenceinterval [CI], 0.967-3.281; P = .048) was found to indepen-dently predict mortality.

Among the organ system failures, respiratory failure wasthe most effective (AUROC, 0.969; 95% CI, 0.941-0.996),followed by cardiovascular failure (AUROC, 0.928; 95%CI, 0.834-1.021), in discriminating survivors and nonsurvi-vors, whereas coagulation failure (AUROC, 0.601; 95% CI,0.433-0.770) was the least effective (Table 2).

4. Discussion

Patients with dengue fever may present with organfailure, and these patients may often require ICU admission.The outcome of these patients is good if appropriate therapyand organ support are instituted. We observed a 28-daymortality of 6.1% in our patient cohort, and admissionAPACHE II score was found to be an independent factorpredicting mortality.

Dengue generally affects the younger population, andother Indian studies have also reported a higher incidence inmales [3,7,8]. It predominantly affects the population living

Table 2 Comparing the ability of various components ofthe SOFA score to discriminate between survivors andnonsurvivors using area under curve

Scoring system AUC 95% CIs

APACHE II 0.995 0.984-1.005Total SOFA score 0.984 0.967-1.000SOFA respiratory 0.969 0.941-0.996SOFA coagulation 0.601 0.433-0.770SOFA cardiovascular system 0.928 0.834-1.021SOFA neurology 0.824 0.660-0.989SOFA hepatobiliary 0.667 0.510-0.823SOFA renal 0.881 0.775-0.988

AUC indicates area under the curve.

in urban and semiurban regions; and fever, myalgia, and anincreased tendency to bleed, which may manifest as hema-turia, rashes, or bleeding from injection sites, are the com-monly reported clinical features of dengue [7,8]. Although amajority of patients exhibit self-limiting disease, it maynot be possible to predict which patient may progress todevelop severe disease [3]. Patients with dengue infectionmay present in the critical phase of their disease exhibited bysevere plasma leakage (causing dengue shock and/or pul-monary edema with respiratory distress), severe hemor-rhages, or severe organ impairment. Organ impairment maymanifest as hepatic or renal impairment, respiratory failure,cardiomyopathy, encephalopathy, or encephalitis [3]. Suchpatients require intensive monitoring and aggressive care inan ICU setup. The outcome of such patients largely dependsupon early recognition and aggressive management of shockand organ failure.

As dengue infection produces a wide range of nonspecificsymptoms, a diagnosis cannot be based only on clinicalsymptoms. An extensive array of laboratory methods areavailable for making a diagnosis that may involve detectionof the virus itself or its nucleic acid, antigens, or antibodies[3]. Laboratory diagnosis may be made early in the diseasecourse by virus isolation or detection of viral nucleic acidor antigen. On the other hand, serology is the method ofchoice in the late phase. Although virus isolation or detec-tion of nucleic acid may be more specific, they are not widelyavailable in the clinical settings, require great technicalexpertise, and are more labor intensive and costly [3]. Hence,detection of viral antigens, like nonstructural protein 1, canbe used for early diagnosis.

As no specific therapy is available, treatment is generallysupportive. Patients may require oxygen support, intensivemonitoring, antipyretics or analgesics, transfusion of plate-let concentrate or blood, adequate hydration, and correctionof electrolyte and metabolic abnormalities. Overall, disease-specific reported case fatality rate is around 1% [3]. But inrural Indian regions with lack of facilities, the reported casefatality rates are between 3% and 5% [3]. The mortality of6.1% in our cohort of dengue patients admitted to ICU is inaccordance with the previous Indian studies that havereported mortality in the range of 7.9% to 11.1% [7,9].Patients with dengue shock syndrome may have a highercase fatality rate of up to 17% [9]. A recent study by Almasand colleagues [10] included 699 dengue patients admitted toa tertiary care hospital and showed that organ failure andbleeding were independent predictors of mortality. However,their mortality rate was lower (2.7%) [10] as compared withours (6.1%), which can be explained by the fact that theyincluded all hospitalized patients, whereas we included onlyICU patients.

Patients with severe dengue infection may have coagu-lation abnormalities, polyserositis leading to pleural effusionand ascites, and shock. These, in turn, may result in hypoxiaand acidosis, which may further lead to cell death andmultiorgan failure. Hence, death in severe dengue infection

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452 D. Juneja et al.

is generally secondary to refractory shock or multiorganfailure [11]. Therefore, severity of illness as assessed byAPACHE II score may determine which patients may haveunfavorable outcome. Coagulation abnormalities, whichmay be very common in patients with dengue fever andmay also necessitate ICU admission in many patients, maynot be a good indicator of overall outcome, as these aregenerally mild and reversible with blood and blood producttransfusions. Massive bleeds leading to further complica-tions and poor outcome can generally be avoided with closemonitoring and platelet transfusions. Timely diagnosis,proper therapy, and careful supervision for deteriorationwould ensure good outcome in such patients. However,presence of other organ failure like cardiovascular or respi-ratory failure may indicate a more severe form of disease andadversely affect outcome in such patients.

4.1. Limitations

It was a single-center study conducted in an urban setupwith advanced facilities; and hence, the results may lackwider applicability. We did not classify our patients accord-ing to the WHO classification [2] because it has been shownto have several shortcomings when applied in clinicalsettings [12].

5. Conclusions

Patients with dengue fever may require ICU admission fororgan failure. Their outcome is good if appropriate aggressivecare and organ support are instituted early. Severity of illness

on ICU admission as assessed by APACHE II score maypredict patients at higher risk of death.

References

[1] WHO. Dengue and dengue haemorrhagic fever. Fact sheet no 117,revised May 2008. Geneva: World Health Organization; 2008. http://www.who.int/mediacentre/factsheets/fs117/en/.

[2] WHO. Dengue haemorrhagic fever: diagnosis, treatment, preventionand control. 2nd ed. Geneva: World Health Organization; 1997.

[3] WHO. Dengue: guidelines for diagnosis, treatment, prevention andcontrol, new ed. Geneva: World Health Organization; 2009.

[4] Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a severity ofdisease classification system. Crit Care Med 1985;13:818-29.

[5] Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-relatedOrgan Failure Assessment) score to describe organ dysfunction/failure.Intensive Care Med 1996;22:707-10.

[6] Makroo RN, Raina V, Kumar P, Kanth RK. Role of platelet trans-fusion in the management of dengue patients in a tertiary care hospital.Asian J Transfus Sci 2007;1:4-7.

[7] Chandralekha, Gupta P, Trikha A. The north Indian dengue outbreak2006: a retrospective analysis of intensive care unit admissions in atertiary care hospital. Trans R Soc Trop Med Hyg 2008;102:143-7.

[8] Khan NA, Azhar EI, El-Fiky S, et al. Clinical profile and outcome ofhospitalized patients during first outbreak of dengue in Makkah, SaudiArabia. Acta Trop 2008;105:39-44.

[9] Shah I, Deshpande GC, Tardeja PN. Outbreak of dengue in Mumbaiand predictive markers for dengue shock syndrome. J Trop Pediatr2004;50:301-5.

[10] Almas A, Parkash O, Akhter J. Clinical factors associated withmortality in dengue infection at a tertiary care center. Southeast AsianJ Trop Med Public Health 2010;41:333-40.

[11] Ranjit S, Kissoon N, Jayakumar I. Aggressive management of dengueshock syndrome may decrease mortality rate: a suggested protocol.Pediatr Crit Care Med 2005;6:412-9.

[12] Bandyopadhyay S, Lum LC, Kroeger A. Classifying dengue: a reviewof the difficulties in using the WHO case classification for denguehaemorrhagic fever. Trop Med Int Health 2006;11:1238-55.