Arun Bansal

Dengue and dengue hemorrhagic fever: management issues in an intensive care unit

OBJECTIVES To describe the epidemiology, clinical features and treatment of dengue fever and dengue shock syndrome. SOURCES To prepare this review, a literature search was made on PubMed and on the World Health Organization (WHO) and PAHO websites using the terms dengue and dengue shock syndrome. This information was complemented with personal practice. SUMMARY OF THE FINDINGS Dengue is the most important arthropod-borne viral disease of humans. Its presentation is protean and varies from an undifferentiated viral syndrome to hemorrhagic fever and severe shock. Dengue fever is a self-limiting, nonspecific illness characterized by fever, headache, myalgia, and constitutional symptoms. Its severe forms (hemorrhagic fever and shock syndrome) may lead to multisystem involvement and death. Early diagnosis, close monitoring for deterioration and response to treatment are necessary in all cases. WHO has provided a stepwise approach to management that is useful for milder forms and early shock. In the more severe forms aggressive fluid resuscitation and support for failing organs is necessary for the critically ill patient. Research addressing pathophysiological differences between dengue shock and septic shock, choice of fluids, inotropes and techniques of organ support are likely to yield benefits for the critically ill. CONCLUSIONS There is no specific therapy for dengue infections. Good supportive care may be lifesaving, but ultimately initiatives aimed at vector control and prevention of mosquito bites may provide the greatest benefits.

Evaluation of efficacy of probiotics in prevention of candida colonization in a PICU-a randomized controlled trial.

Objective:To evaluate the efficacy of probiotics in prevention of Candida colonization in a PICU. Design:Prospective double blinded, randomized controlled trial. Setting:PICU of a tertiary care teaching hospital in north India. Subjects:One hundred fifty children (106 boys, 44 girls), 3 months to 12 yrs old, on broad spectrum antibiotics for at least 48 hrs were randomized using computer-generated random numbers to receive probiotic mix (EUGI) (n = 75) or placebo (n = 75). Intervention:Patients received one sachet twice a day of either probiotics or placebo for 7 days. Probiotics contained Lactobacillus acidophillus, Lactobacillus rhamnosum, Bifidobacterium longum, Bifidobacterium bifidum, Saccharomyces boulardi, Saccharomyces thermophilus, fructo-oligosaccharides; and placebo-contained lactose packed in similar-looking sachets. Rectal swabs for fungal culture were taken at day 0, 7, and 14 of enrollment. Primary outcome measure was prevalence of rectal colonization with Candida on day 14 postenrollment; secondary outcomes were growth of Candida in urine (candiduria) and blood (candidemia). Patients were followed until completion of 14 days study period or death of patient. Results:Demographic and clinical variables were comparable in two groups. Prevalence of Candida colonization on day 0 was similar (15 of 75) in both the groups. On day 7, 27.9% (19 of 68) patients in the probiotic group and 42.6% (29 of 68) patients in the placebo group were colonized (relative risk 0.65; 95% confidence interval 0.41–1.05; p = 0.07), whereas, on day 14, colonization was observed in 31.3% (21 of 67) patients in the probiotic group and 50% (34 of 68) in the placebo group (relative risk 0.63; 95% confidence interval 0.41–0.96; p = 0.02). Thus, the relative reduction in prevalence of Candida colonization on day 7 and 14 in the probiotic group was 34.5% and 37.2%, respectively. The increase in number of colonized patients from day 0 to 7 and day 0 to 14 was significant in the placebo group (p = 0.004 and 0.001, respectively) but not in the probiotic group (p = 0.30 and 0.19, respectively; McNemar test). Candiduria was significantly less common in the probiotic group than in the placebo group (17.3% vs. 37.3%; relative risk 0.46; 95% confidence interval 0.26–0.82; p = 0.006). However, prevalence of candidemia did not differ significantly in two groups (1.6% in the probiotic group vs. 6.35% in placebo group; relative risk 0.46; 95% confidence interval 0.08–2.74; p = 0.39). Conclusions:Supplementation with probiotics could be a potential strategy to reduce gastrointestinal Candida colonization and candiduria in critically ill children receiving broad spectrum antibiotics.

Non traumatic coma

Objective: To study the etiology and clinical profile of non-traumatic coma in children and to determine the clinical signs predictive of outcome.Methods: 100 consecutive cases of nontraumatic coma between 2 months to 12 years. Clinical signs studied were temperature, pulse, heart rate, blood pressure, coma severity by Glasgow coma scale (GCS), respiratory pattern, pupillary and corneal reflex, extra ocular movements, motor patterns, seizure types and fundus picture. These were recoded at admission and after 48 hours of hospital stay. Etiology of coma was determined on basis of clinical history, examination and relevant laboratory investigations by the treating physician. The outcome was recorded as survived or died, and among those who survived as normal, mild, moderate, or severe disability. Chi-square test and logistic regression analysis were done to determine predictors of outcome.Results: Etiology of coma in 60% cases was CNS infection (tubercular meningitis19, encephalitis18, bacterial meningitis16, others7); other causes were toxic-metabolic conditions (19%), status epilepticus (10%), intracranial bleed (7%), and miscellaneous (4%). 65 children survived, 11 were normal, 14 had mild disability, 21 had moderate disability and 14 were severely disabled and dependent. Survival was significantly better in patients with CNS infection (63%) as compared to those with toxic-metabolic causes (27%) and intracranial bleed (43%, P < 0.05). On bivariate analysis age <-3 years, poor pulse volume, abnormal respiratory pattern and apnoea, abnormal pupillary size and reaction, abnormal extra ocular movements, absent corneal reflex, abnormal motor muscle tone at admission or 48 hours correlated significantly with mortality. Survival was better with increasing GCS (Spearman rho =. 32, P < 0.001). On logistic regression age < 3 years, poor pulse volume, absent extraocular movements and papilloedema at admission and 48 hours after admission were independent significant predictors of death.Conclusion: CNS infections were the most common cause of non-traumatic coma in childhood. Simple clinical signs were good predictors of outcome

Randomised comparison of intravenous magnesium sulphate, terbutaline and aminophylline for children with acute severe asthma

This study compared the efficacy of intravenous magnesium sulphate, terbutaline and aminophylline for children with acute, severe asthma poorly responsive to standard initial treatment.

Dengue e dengue hemorrágico: aspectos do manejo na unidade de terapia intensiva

OBJECTIVES: To describe the epidemiology, clinical features and treatment of dengue fever and dengue shock syndrome. SOURCES: To prepare this review, a literature search was made on Pubmed and on the World Health Organization (WHO) and PAHO websites using the terms dengue and dengue shock syndrome. This information was complemented with personal practice. SUMMARY OF THE FINDINGS: Dengue is the most important arthropod-borne viral disease of humans. Its presentation is protean and varies from an undifferentiated viral syndrome to hemorrhagic fever and severe shock. Dengue fever is a self-limiting, nonspecific illness characterized by fever, headache, myalgia, and constitutional symptoms. Its severe forms (hemorrhagic fever and shock syndrome) may lead to multisystem involvement and death. Early diagnosis, close monitoring for deterioration and response to treatment are necessary in all cases. WHO has provided a stepwise approach to management that is useful for milder forms and early shock. In the more severe forms aggressive fluid resuscitation and support for failing organs is necessary for the critically ill patient. Research addressing pathophysiological differences between dengue shock and septic shock, choice of fluids, inotropes and techniques of organ support are likely to yield benefits for the critically ill. CONCLUSIONS: There is no specific therapy for dengue infections. Good supportive care may be lifesaving, but ultimately initiatives aimed at vector control and prevention of mosquito bites may provide the greatest benefits.

Etiology of community acquired pneumonia among children in India: prospective, cohort study.

Background Childhood community acquired pneumonia (CAP) is a significant problem in developing countries, and confirmation of microbial etiology is important for individual, as well as public health. However, there is paucity of data from a large cohort, examining multiple biological specimens for diverse pathogens (bacteria and viruses). The Community Acquired Pneumonia Etiology Study (CAPES) was designed to address this knowledge gap. Methods We enrolled children with CAP (based on WHO IMCI criteria of tachypnea with cough or breathing difficulty) over 24 consecutive months, and recorded presenting symptoms, risk factors, clinical signs, and chest radiography. We performed blood and nasopharyngeal aspirate (NPA) bacterial cultures, and serology (Mycoplasma pneumoniae, Chlamydophila pneumoniae). We also performed multiplex PCR for 25 bacterial/viral species in a subgroup representing 20% of the cohort. Children requiring endotracheal intubation underwent culture and PCR of bronchoalveolar lavage (BAL) specimens. Findings We enrolled 2345 children. NPA and blood cultures yielded bacteria in only 322 (13.7%) and 49 (2.1%) children respectively. In NPA, Streptococcus pneumoniae (79.1%) predominated, followed by Haemophilus influenzae (9.6%) and Staphylococcus aureus (6.8%). In blood, S. aureus (30.6%) dominated, followed by S. pneumoniae (20.4%) and Klebsiella pneumoniae (12.2%). M. pneumoniae and C. pneumoniae serology were positive in 4.3% and 1.1% respectively. Multiplex PCR in 428 NPA specimens identified organisms in 422 (98.6%); of these 352 (82.2%) had multiple organisms and only 70 (16.4%) had a single organism viz. S. pneumoniae: 35 (50%), Cytomegalovirus (CMV): 13 (18.6%), Respiratory Syncytial Virus (RSV): 9 (12.9%), other viruses: 6 (8.7%), S. aureus: 5 (7.1%), and H. influenzae: 2 (2.9%). BAL PCR (n = 30) identified single pathogens in 10 (S. pneumoniae–3, CMV–3, S. aureus–2, H. influenzae–2) and multiple pathogens in 18 children. There were 108 (4.6%) deaths. The pattern of pathogens identified did not correlate with pneumonia severity or mortality. Conclusions The majority of children with CAP have multiple pathogens (bacteria and viruses). S. pneumoniae and S. aureus predominate in NPA and blood respectively. CMV and RSV were the dominant respiratory viruses in NPA and BAL. The presence of multiple pathogens, especially organisms associated with nasopharyngeal carriage, precludes confirmation of a causal relationship in most cases.

Low-Dose vs Standard-Dose Insulin in Pediatric Diabetic Ketoacidosis A Randomized Clinical Trial

IMPORTANCE The standard recommended dose (0.1 U/kg per hour) of insulin in diabetic ketoacidosis (DKA) guidelines is not backed by strong clinical evidence. Physiologic dose-effect studies have found that even lower doses could adequately normalize ketonemia and acidosis. Lowering the insulin dose may be advantageous in the initial hours of therapy when a gradual decrease in glucose, electrolytes, and resultant osmolality is desired. OBJECTIVE To compare the efficacy and safety of low-dose insulin against the standard dose in children with DKA. DESIGN, SETTING, AND PARTICIPANTS This was a prospective, open-label randomized clinical trial conducted in the pediatric emergency department and intensive care unit of a tertiary care teaching hospital in northern India from November 1, 2011, through December 31, 2012. A total of 50 consecutive children 12 years or younger with a diagnosis of DKA were randomized to low-dose (n = 25) and standard-dose (n = 25) groups. INTERVENTIONS Low-dose (0.05 U/kg per hour) vs standard-dose (0.1 U/kg per hour) insulin infusion. MAIN OUTCOMES AND MEASURES The primary outcome was the rate of decrease in blood glucose until a level of 250 mg/dL or less is reached (to convert to millimoles per liter, multiply by 0.0555). The secondary outcomes included time to resolution of acidosis, episodes of treatment failures, and incidences of hypokalemia and hypoglycemia. RESULTS The mean (SD) rate of blood glucose decrease until a level of 250 mg/dL or less is reached (45.1 [17.6] vs 52.2 [23.4] mg/dL/h) and the mean (SD) time taken to achieve this target (6.0 [3.3] vs 6.2 [2.2] hours) were similar in the low- and standard-dose groups, respectively. Mean (SD) length of time to achieve resolution of acidosis (low vs standard dose: 16.5 [7.2] vs 17.2 [7.7] hours; P = .73) and rate of resolution of acidosis were also similar in the groups. Hypokalemia was seen in 12 children (48%) receiving the standard dose vs 5 (20%) of those receiving the low dose (P = .07); the tendency was more pronounced in malnourished children (7 [88%] vs 2 [28%]). Five children (20%) and 1 child (4%) receiving standard- and low-dose infusion (P = .17), respectively, developed hypoglycemia. Treatment failure was rare and comparable. One child in the standard-dose group developed cerebral edema, and no deaths occurred during the study period. CONCLUSIONS AND RELEVANCE Low dose is noninferior to standard dose with respect to rate of blood glucose decrease and resolution of acidosis. We advocate a superiority trial with a larger sample size before 0.05 U/kg per hour replaces 0.1 U/kg per hour in the practice recommendations. TRIAL REGISTRATION ctri.nic.in Identifier: CTRI/2012/04/002548.

Randomized controlled trial comparing cerebral perfusion pressure-targeted therapy versus intracranial pressure-targeted therapy for raised intracranial pressure due to acute CNS infections in children.

Objective:In children with acute CNS infection, management of raised intracranial pressure improves mortality and neuromorbidity. We compared cerebral perfusion pressure–targeted approach with the conventional intracranial pressure–targeted approach to treat raised intracranial pressure in these children. Design:Prospective open-label randomized controlled trial. Setting:PICU in a tertiary care academic institute. Patients:Hundred ten children (1–12 yr) with acute CNS infections having raised intracranial pressure and a modified Glasgow Coma Scale score less than or equal to 8 were enrolled. Interventions:Patients were randomized to receive either cerebral perfusion pressure–targeted therapy (n = 55) (maintaining cerebral perfusion pressure ≥ 60 mm Hg, using normal saline bolus and vasoactive therapy—dopamine, and if needed noradrenaline) or intracranial pressure–targeted therapy (n = 55) (maintaining intracranial pressure < 20 mm Hg using osmotherapy while ensuring normal blood pressure). The primary outcome was mortality up to 90 days after discharge from PICU. Secondary outcome was modified Glasgow Coma Scale score at 72 hours after enrollment, length of PICU stay, duration of mechanical ventilation, and hearing deficit and functional neurodisability at discharge and 90-day follow-up. Measurements and Main Results:A 90-day mortality in intracranial pressure group (38.2%) was significantly higher than cerebral perfusion pressure group (18.2%; relative risk = 2.1; 95% CI, 1.09–4.04; p = 0.020). The cerebral perfusion pressure group in comparison with intracranial pressure group had significantly higher median (interquartile range) modified Glasgow Coma Scale score at 72 hours (10 [8–11] vs 7 [4–9], p < 0.001), shorter length of PICU stay (13 d [10.8–15.2 d] vs 18 d [14.5–21.5 d], p = 0.002) and mechanical ventilation (7.5 d [5.4–9.6 d] vs 11.5 d [9.5–13.5 d], p = 0.003), lower prevalence of hearing deficit (8.9% vs 37.1%; relative risk = 0.69; 95% CI, 0.53–0.90; p = 0.005), and neurodisability at discharge from PICU (53.3% vs 82.9%; relative risk = 0.37; 95% CI, 0.17–0.81; p = 0.005) and 90 days after discharge (37.8% vs 70.6%; relative risk = 0.47; 95% CI, 0.27–0.83; p = 0.004). Conclusion:Cerebral perfusion pressure–targeted therapy, which relied on more frequent use of vasopressors and lesser use of hyperventilation and osmotherapy, was superior to intracranial pressure–targeted therapy for management of raised intracranial pressure in children with acute CNS infection in reducing mortality and morbidity.

Vitamin D deficiency in critically ill children with sepsis.

Background: Data on the prevalence of vitamin D deficiency (VDD) in critically ill children with sepsis and its association with illness severity and outcome are limited. Aim: To investigate the prevalence of VDD in critically ill children with sepsis. Methods: One hundred and twenty-four critically ill children with sepsis aged 1–12 years were prospectively enrolled in a paediatric intensive care unit (PICU) in North India over a 1-year period. Demographic data, clinical signs and risk factors for VDD, Paediatric Index of Mortality III (PRISM III) score, and sequential organ failure assessment (SOFA) score were recorded. Plasma 25-hydroxy vitamin D [25(OH)D] levels were measured by ELISA within 24 hours of admission. The occurrence of septic shock, multiple organ dysfunction syndrome (MODS) and healthcare-associated infection (HCAI), need for mechanical ventilation and catecholamines, length of PICU stay and mortality were also recorded. Cases were compared with 338 apparently healthy children for baseline variables and vitamin D status. Results: Prevalence of VDD [25(OH)D level < 50 nmol/L] was higher among critically ill children with sepsis compared to healthy controls (50.8% vs 40.2%, P = 0.04). VDD was not associated with any significant difference in baseline demographic variables or risk factors for VDD. Although there was a trend toward increased PRISM III score, septic shock, MODS, HCAI, need for mechanical ventilation and catecholamines, length of PICU stay, and mortality, the difference was not statistically significant. Conclusion: A high prevalence of VDD in critically ill children with sepsis was found but it was not associated with greater severity of illness or other clinical outcomes.

Probiotic use and prevalence of candidemia and candiduria in a PICU.

Objectives: To compare the prevalence of candidemia and candiduria before and after the introduction of routine use of probiotics in children who received broad-spectrum antibiotics in a PICU. Design: Retrospective “before and after” study. Setting: A 12-bed PICU of a teaching hospital in India. Patients: Children 3 months to 12 years old, admitted to the PICU over two 9 months’ time periods, who received broad-spectrum antibiotics for more than 48 hours. Interventions: Three hundred forty-four patients enrolled between November 2008 and July 2009 after the introduction of routine use of probiotics served as the “probiotic group”; they had received one sachet twice a day of a probiotic mix (EUGI [Wallace Pharma, Goa, India] containing Lactobacillus acidophillus, Lactobacillus rhamnosum, Bifidobacterium longum, Bifidobacterium bifidum, Saccharomyces boulardii, and Streptococcus thermophilus) for 7 days. Three hundred seventy-six children enrolled between February 2007 and October 2007 served as “controls.” Blood was sent for bacterial and fungal cultures if clinically indicated and urine catheter/bag specimen was submitted for bacterial and fungal culture twice a week as per unit’s protocol. Measurements and Main Results: Primary outcome was growth of Candida in blood (candidemia), and secondary outcomes were growth of Candida in urine (candiduria), nosocomial bloodstream infections, and urinary tract infections. Data were retrieved from the case records. Candidemia was seen in four of 344 patients (1.2%) in the probiotic group and in 14 of 376 (3.7%) in the control group (relative risk, 0.31; 95% CI, 0.10–0.94; p = 0.03). Candiduria was noted in 37 of 344 patients (10.7%) in the probiotic group and 83 of 376 (22%) in the control group (relative risk, 0.48; 95% CI, 0.34–0.7; p = 0.0001). The prevalence of nosocomial bloodstream infection and urinary tract infection in the probiotic and control groups was 20.3% and 26% (p = 0.07) and 14.2% and 19.1% (p = 0.08), respectively. Conclusions: Routine use of a mix of probiotics in patients who receive broad-spectrum antibiotics could be a useful strategy to reduce the prevalence of candidemia and candiduria in the PICU.