Objectives:To provide a comprehensive review of dengue, with an emphasis on clinical syndromes, classification, diagnosis, and management, and to outline relevant aspects of epidemiology, immunopathogenesis, and prevention strategies. Dengue, a leading cause of childhood mortality in Asia and South

Dengue hemorrhagic fever and shock syndromes.

Dengue counts among the most commonly encountered arboviral diseases, representing the fastest spreading tropical illness in the world. It is prevalent in 128 countries, and each year >2.5 billion people are at risk of dengue virus infection worldwide. Neurological signs of dengue infection are increasingly reported. In this review, the main neurological complications of dengue virus infection, such as central nervous system (CNS), peripheral nervous system, and ophthalmic complications were discussed according to clinical features, treatment and possible pathogenesis. In addition, neurological complications in children were assessed due to their atypical clinical features. Finally, dengue infection and Japanese encephalitis were compared for pathogenesis and main clinical manifestations.

/pdf/neurological-manifestations-of-dengue-infection-2mxcqvc6bo.pdf

Neurological Manifestations of Dengue Infection

OBJECTIVE Clinicians in resource-poor countries need to identify patients with dengue using readily-available data. The objective of this systematic review was to identify clinical and laboratory features that differentiate dengue fever (DF) and/or dengue haemorrhagic fever (DHF) from other febrile illnesses (OFI) in dengue-endemic populations. METHOD Systematic review of the literature from 1990 to 30 October 2007 including English publications comparing dengue and OFI. RESULTS Among 49 studies reviewed, 34 did not meet our criteria for inclusion. Of the 15 studies included, 10 were prospective cohort studies and five were case-control studies. Seven studies assessed all ages, four assessed children only, and four assessed adults only. Patients with dengue had significantly lower platelet, white blood cell (WBC) and neutrophil counts, and a higher frequency of petechiae than OFI patients. Higher frequencies of myalgia, rash, haemorrhagic signs, lethargy/prostration, and arthralgia/joint pain and higher haematocrits were reported in adult patients with dengue but not in children. Most multivariable models included platelet count, WBC, rash, and signs of liver damage; however, none had high statistical validity and none considered changes in clinical features over the course of illness. CONCLUSIONS Several individual clinical and laboratory variables distinguish dengue from OFI; however, some variables may be dependent on age. No published multivariable model has been validated. Study design, populations, diagnostic criteria, and data collection methods differed widely across studies, and the majority of studies did not identify specific aetiologies of OFIs. More prospective studies are needed to construct a valid and generalizable algorithm to guide the differential diagnosis of dengue in endemic countries.

/pdf/clinical-and-laboratory-features-that-distinguish-dengue-29jmqutmog.pdf

Clinical and laboratory features that distinguish dengue from other febrile illnesses in endemic populations.

Background 
The pathogenesis of dengue shock syndrome (DSS, grade 3 and 4) is not yet completely understood. Several factors are reportedly associated with DSS, a more severe form of dengue infection that reportedly causes 50 times higher mortality compared to that of dengue patients without DSS. However, the results from these reports remain inconclusive. To better understand the epidemiology, clinical manifestation, and pathogenesis of DSS for development of new therapy, we systematically reviewed and performed a meta-analysis of relevant studies that reported factors in both DSS and dengue hemorrhagic fever (DHF, grade 1 and 2) patients.
Methods and Findings 
PubMed, EMBASE, Scopus, Google Scholar, Dengue Bulletin, Cochrane Library, Virtual Health Library, and a manual search of reference lists of articles published before September 2010 were used to retrieve relevant studies. A meta-analysis using fixed- or random-effects models was used to calculate pooled odds ratios (OR) or event rate with corresponding 95% confidence intervals. Assessment of heterogeneity and publication bias, meta-regression analysis, subgroup analysis, sensitivity analysis, and analysis of factor-specific relationships were further performed. There were 198 studies constituting 203 data sets that met our eligibility criteria. Our meta-regression analysis showed a sustained reduction of DSS/dengue hemorrhagic fever (DHF) ratio over a period of 40 years in Southeast Asia, especially in Thailand. The meta-analysis revealed that age, female sex, neurological signs, nausea/vomiting, abdominal pain, gastrointestinal bleeding, hemoconcentration, ascites, pleural effusion, hypoalbuminemia, hypoproteinemia, hepatomegaly, levels of alanine transaminase and aspartate transaminase, thrombocytopenia, prothrombin time, activated partial thromboplastin time, fibrinogen level, primary/secondary infection, and dengue virus serotype-2 were significantly associated with DSS when pooling all original relevant studies.
Conclusions 
The results improve our knowledge of the pathogenesis of DSS by identifying the association between the epidemiology, clinical signs, and biomarkers involved in DSS.

/pdf/factors-associated-with-dengue-shock-syndrome-a-systematic-1f70gob7m8.pdf

Factors Associated with Dengue Shock Syndrome: A Systematic Review and Meta-Analysis

Purpose
To provide clinicians practicing in resource-limited settings with a framework to improve the diagnosis and treatment of pediatric and adult patients with sepsis.

/pdf/recommendations-for-sepsis-management-in-resource-limited-5vmlnyzfft.pdf

Recommendations for sepsis management in resource-limited settings.

The objective was to review clinical features and outcome of children with severe forms of dengue hemorrhagic fever (DHF) presenting to a pediatric intensive care unit (PICU) with particular focus on clinical presentation and outcome. Retrospective chart review of patients admitted to the Pediatric Intensive Care Unit (PICU) of a referral childrens hospital in South India with DHF over 1.5 years (2001-January 2003). Of 858 patients with dengue fever/DHF admitted to the hospital during the study period 109 cases with severe forms of disease required PICU admission of which 9 patients died. 77 were under 5 years of age. The commonest indication for PICU admission was persistent shock (39 patients) followed by requirement for positive pressure ventilation in 29 patients (10 of whom had Acute Respiratory Distress Syndrome [ARDS]) and neurological symptoms in 24 patients. An important finding was the presence of diastolic dysfunction in 3 children. Six deaths of refractory shock included 4 who had ARDS and DIC and 2 who had shock with DIC 3 patients had abdominal compartment syndrome (ACS) has not been previously described in children with DSS and may lead to fluid refractory shock if not corrected. All patients had thrombocytopenia which was a defining feature of the syndrome while 74 were also coagulopathic and 6 had severe fatal DIC. Hepatic dysfunction was more severe in children with prolonged shock however only a fifth of cases (5/24) with neurological manifestations were in shock. Other significant reasons for neurological presentation included cerebral edema and encephalopathy secondary to hepatic dysfunction. 2 children had features of Acute Disseminated Encephalomyelitis (ADEM) previously only described in adults with dengue. It was found that complications such as DIC diastolic dysfunction abdominal compartment syndrome ARDS and hepatic dysfunction were more frequent in severe established shock. However most neurological events were unrelated to the perfusion status. Children referred late were harder to resuscitate. There were 9 PICU deaths (case fatality rate of 8.35%). Severe refractory shock DIC ARDS hepatic failure and neurological manifestations singly or in combination were the commonest causes of death in the present study. (authors)

/pdf/clinical-features-complications-and-atypical-manifestations-4684yy6j0v.pdf

Clinical features, complications and atypical manifestations of children with severe forms of dengue hemorrhagic fever in South India.

OBJECTIVE To compare the clinical, hemodynamic, and laboratory variables, treatment, and outcome in dengue shock syndrome (DSS) and septic shock (SS), with an aim to permit early differentiation at presentation to the emergency department. DESIGN Retrospective chart review. SETTING A tertiary care pediatric emergency and critical care unit. PATIENTS Thirty-two patients (16 DSS and 16 SS) between June 2004 and December 2005 who were treated in the emergency department and intensive care using protocols. INTERVENTIONS None. RESULTS There were no differences between groups in terms of age, number with decompensated shock, and Pediatric Risk of Mortality III scores. Differences between DSS and SS were found in heart rate, 120 +/- 39 beats per minute versus 158 +/- 35 beats per minute (P < 0.01); pulse pressures, 25 +/- 8 mm Hg versus 43 +/- 8 mm Hg (P < 0.01); presence of systemic inflammatory response syndrome, 9/16 versus 15/16 (P < 0.05); Glasgow Coma Score, 13 +/- 3 versus 10 +/- 4 (P < 0.05); hematocrit, 42 +/- 6 versus 29 +/- 7 (P < 0.01); and median platelet count, 29,000/mm3 (interquartile range, 20,500-57,500/mm3) versus 115,500/mm3 (interquartile range, 91,750-182,250/mm3 in SS) (P < 0.01). Patients with SS were more likely to require greater than 40 mL/kg of fluid for initial resuscitation, ventilation, and vasoactive support for shock compared with those with dengue. In the fluid and catecholamine refractory patients, 6 of 16 SS versus 0 of 16 DSS patients were treated with steroids (P < 0.05). The outcome was similar in both groups, with 2 of 16 deaths among children with SS and 1 of 16 in those with DSS. CONCLUSIONS Dengue shock syndrome is likely a distinct entity from SS with some overlapping features. The DSS patients are significantly less likely to have systemic inflammatory response syndrome, be tachycardic, and have a narrower pulse pressure at admission when compared with SS patients. Mental status is better preserved, and spontaneous clinical bleeding is more common in children with DSS compared with those in SS. These likely results from the predominantly vasodilatory state in SS versus vasoconstrictory state that is the initial response in DSS.

Early differentiation between dengue and septic shock by comparison of admission hemodynamic, clinical, and laboratory variables: a pilot study.

Objective: To determine whether physicians were aware of and had the skills to implement the American College of Critical Care Medicine/Pediatric Advanced Life Support Course septic shock protocol. Design: A cross-sectional questionnaire survey. Setting: Four academic institutions in Chennai, Manipal, Mangalore, and Trivandrum - cities representing the three southern states of Tamil Nadu, Karnataka, and Kerala, respectively, between February and April 2006. Interventions: Pre and post lecture questions. They were evaluated using 11 questions testing knowledge and 10 questions testing their comfort level in performing interventions related to the initial resuscitation in septic shock. Measurement and Main Result: The ACCM/PALS sepsis guidelines were taught during the PALS course conducted in the four academic institutions. A total of 118 delegates participated, of whom 114 (97%) were pediatricians and four (3%) were anaesthetists. The overall mean number of correct responses for the 11 questions testing knowledge before and after the lecture was 2.1 and 4.07, respectively P =0.001(paired t test). Although, 42% of the respondents (n=50) were aware of the ACCM guidelines, 88% (n=104) did not adhere to it in their practice. A total of 86% (n=101) and 66% (n=78) did not feel comfortable titrating inotropes or intubating in the ED; 78% (n=92) and 67% (n=78), respectively felt that central venous access (CVA) and arterial pressure (AP) monitoring were unimportant in the management of fluid refractory shock. Of the physicians, 20% (n=24) had never intubated a patient, 78% (n=92) had not introduced a central venous catheter, and 76% (n=90) had never introduced an intra-arterial catheter. Conclusions: In view of the lack of skills and suboptimal knowledge, the ACCM/PALS sepsis guidelines may be inappropriate in its current format in the Indian setting. More emphasis needs to be placed on educating community pediatricians with a simpler clinical protocol, which has the potential to save many more children.

GAP between knowledge and skills for the implementation of the ACCM/PALS septic shock guidelines in India: is the bridge too far?

Kamath, S. R.1; Ramasamy, H.1; Surya, K.1; Shah, P.1; Alkaby, L.2; Ali, M.2 Author Information 

PP310 [Heart » Heart]: COMPARATIVE ANALYSIS OF CASE SERIES OF CLASSICAL TETRALOGY OF FALLOT (TOF) WITH TOF WITH SUB-ARTERIAL VENTRICULAR SEPTAL DEFECT TYPE

How to cite this article: Kamath SR. Multidrug Resistance: The Growing Menace in PICU. Indian J Crit Care Med 2023;27(1):6–7.

/pdf/multidrug-resistance-the-growing-menace-in-picu-3cll82kw.pdf

Shrishu R Kamath

Papers

Clinical features, complications and atypical manifestations of children with severe forms of dengue hemorrhagic fever in South India.

Early differentiation between dengue and septic shock by comparison of admission hemodynamic, clinical, and laboratory variables: a pilot study.

GAP between knowledge and skills for the implementation of the ACCM/PALS septic shock guidelines in India: is the bridge too far?

PP310 [Heart » Heart]: COMPARATIVE ANALYSIS OF CASE SERIES OF CLASSICAL TETRALOGY OF FALLOT (TOF) WITH TOF WITH SUB-ARTERIAL VENTRICULAR SEPTAL DEFECT TYPE

Multidrug Resistance: The Growing Menace in PICU