Prevalence and outcome of diastolic dysfunction in children with fluid refractory septic shock--a prospective observational study.

OBJECTIVES: Our primary objective was to determine the prevalence and outcome of diastolic dysfunction in children with fluid refractory septic shock. The secondary objective was to determine possible early predictors of diastolic dysfunction. DESIGN: Prospective observational study. SETTING: PICU of a tertiary care teaching hospital. PATIENTS: Consecutive children 17 years old or younger with fluid refractory septic shock and not on mechanical ventilation admitted to our ICU from June 2011 to August 2012 were included. Survivors were followed up till 1 year of discharge (July 2013). INTERVENTIONS: Children were subjected to 2D echocardiography and qualitative cardiac troponin-T test within the first 6 hours of admission. MEASUREMENTS AND MAIN RESULTS: A total of 56 children were included. Median age was 7 years (interquartile range, 1.5, 14) and majority (52%) were males. Most common underlying diagnoses were meningitis and pneumonia. The prevalence of diastolic dysfunction was 41.1% (95% CI, 27.8-54.4), and mortality rate was 43% in those with diastolic dysfunction. At 1-year follow-up, residual dysfunction was present in only one of 11 of the survivors (11%). On univariable analysis of possible early predictors of diastolic dysfunction, we observed that these children tended to have higher mean central venous pressure (13 vs 6; p < 0.0001) and greater positivity for cardiac troponin-T (70% vs 36%; p = 0.01) compared with others. Although factors such as duration of illness and diastolic blood pressure were also lower in children with diastolic dysfunction compared with others, the difference was not statistically significant. On multivariable analysis, only the variable central venous pressure remained significant (adjusted odds ratio, 1.6; 95% CI, 1.12-2.14; p = 0.008). CONCLUSIONS: Diastolic dysfunction is common in children with fluid refractory septic shock, and immediate outcomes may be poorer in such patients. Increased central venous pressure after initial fluid resuscitation may be an early indicator of diastolic dysfunction and warrant urgent bedside echocardiography to guide further management.

Pediatric Index of Mortality and PIM2 scores have good calibration in a large cohort of children from a developing country.

OBJECTIVE: Our objective was to validate the Pediatric Index of Mortality (PIM) and PIM2 scores in a large cohort of children from a developing country. DESIGN: Prospective observational study. SETTING: Pediatric intensive care unit of a tertiary care teaching hospital. PATIENTS: All children aged <18 years admitted between June 2011 and July 2013. MEASUREMENTS AND MAIN RESULTS: We evaluated the discriminative ability and calibration as measured by the area under the receiver operating characteristic (ROC) curves, the Hosmer-Lemeshow goodness-of-fit (GOF), and standardized mortality ratio (SMR), respectively. Of the 819 children enrolled, 232 (28%) died. The median (IQR) age of the study subjects was 4 years (0.8, 10). The major reasons for ICU admission as well as mortality were sepsis/severe sepsis. The area under ROC curves for PIM and PIM2 was 0.72 (95% CI: 0.67-0.75) and 0.74 (95% CI: 0.70-0.78), respectively. The goodness-of-fit test showed a good calibration across deciles of risk for the two scores with P values being >0.05. The SMR (95% CI) was 0.99 (0.85-1.15) and 1 (0.85-1.16) for PIM and PIM2, respectively. The calibration across different age and diagnostic subgroups was also good. CONCLUSION: PIM and PIM2 scores had good calibration in our setup.

Postnatal changes in cerebral blood flow velocity in term intra-uterine growth-restricted neonates.

BACKGROUND: Intra-uterine growth-restricted (IUGR) fetuses are prone to hypoxic changes in the brain and neurodevelopmental sequelae in later life. Chronic hypoxaemia may also lead to polycythaemia in the fetal and neonatal period. AIM: To evaluate venous haematocrit and cerebral blood flow velocity (CBFV) in term IUGR neonates in the immediate postnatal period. METHODS: This was a prospective observational study of 54 clinically healthy term IUGR neonates as cases and 50 term, appropriate-for-gestational-age (AGA), healthy neonates as controls. IUGR was defined as birthweight <10th per centile for gestational age. Neonates with perinatal asphyxia, sepsis and other systemic diseases were excluded. Resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV) and vascular diameter were measured in the internal carotid, vertebral and middle cerebral arteries by transcranial colour Doppler ultrasound between 48 and 72 hours of life, along with the estimation of venous haematocrit. Neonates were observed for development of any complications until discharge and followed up clinically and radiologically for a minimum 6 months. RESULTS: Significantly higher resistance (RI and PI) and lower PSV was recorded in all the cerebral arteries of the IUGR than the AGA group whereas no difference was observed in vascular diameters. Mean haematocrit was significantly higher in the IUGR than in the AGA group [55·7 (4·22) vs 45·1 (2·79) g/dl]. Haematocrit was positively correlated with RI and PI, and negatively correlated with PSV. After discharge, three infants in the IUGR group showed hypertonia and delayed developmental milestones along with hypoxic changes in MRI of the brain. CONCLUSIONS: Compared with their AGA counterparts, higher venous haematocrit and lower CBFV were observed in clinically healthy, term IUGR neonates during the early neonatal period. Delayed developmental milestones and hypoxic changes were detected by MRI in three infants. Since the study was limited by its sample size, larger studies are required to document the clinical significance of decreased CBFV and its usefulness as a marker of poor prognosis for future neurodevelopment.

Thymic involution as a predictor of early-onset neonatal sepsis.

BACKGROUND: Diagnosis of early-onset neonatal sepsis (EONS) is often difficult because of vague clinical signs and non-specific laboratory parameters. OBJECTIVE: To assess the statistical validity of thymic size estimation as a diagnostic marker of EONS compared with cord blood interleukin-6 (IL-6) concentrations. SUBJECTS AND METHODS: Thirty-two neonates delivered in hospital and admitted to the neonatal unit with EONS comprised the study group. EONS was diagnosed on the basis of development of clinical signs and symptoms of sepsis within 72 hours of birth in the presence of antenatal risk factors for chorio-amnionitis and a positive blood culture. Thirty-two gestational age- and gender-matched healthy neonates served as controls. Cord blood IL-6 concentrations were estimated by ELISA. Thymic size was assessed by sonological measurement of thymic dimensions (longitudinal and transverse diameters, thymic volume and thymic index) within 24 hours of birth in the study infants and the controls. Data were analyzed by SPSS 16.0. RESULTS: Thymic size was significantly smaller whereas cord blood IL-6 concentrations were significantly higher (P<0.001) in the sepsis group than in the controls. Sensitivity and specificity of thymic dimensions were comparable to IL-6 concentrations for diagnosing EONS. Significant correlation was noted between reduction in thymic size and a rise in IL-6 concentrations. CONCLUSION: Thymic involution can be used as a reliable diagnostic marker for EONS.

Cerebral blood flow velocity in early-onset neonatal sepsis and its clinical significance.

Chorioamnionitis is a known risk factor for neurological damage in newborns. The present study aimed at assessing the changes in cerebral blood flow velocity (CBFV) in early-onset neonatal sepsis (EONS) and determining its predictive value as well as prognostic significance. Inborn neonates with antenatal risk factors for chorioamnionitis were followed up for development of EONS, diagnosed by presence of clinical signs along with positive blood culture and/or elevated interleukin-6 (IL-6) concentrations (≥50 pg/mL) in umbilical cord blood. Comparison group was formed by asymptomatic neonates who had risk factors for chorioamnionitis but did not develop EONS and cord blood IL-6 concentrations were <50 pg/mL. CBFV (resistance and pulsatility indices, peak systolic flow velocity, and vascular diameter) of internal carotid, vertebral, and middle cerebral arteries was assessed by transcranial Doppler ultrasonography within 24 h of birth. The babies were kept under clinical and radiological follow-up for a minimum period of 6 months. Data were analyzed by SPSS 16.0. Final study group contained 55 neonates with sepsis and 35 asymptomatic control neonates. Blood culture was positive in 27 babies of the sepsis group with a preponderance of Gram-negative bacterial isolation. Significantly lower resistance, vasodilatation, and higher blood flow were noted in all the cerebral arteries of the sepsis group. Increase in CBFV was correlated with elevated IL-6 concentrations. CBFV parameters showed significant predictive accuracy as early diagnostic markers of EONS. Among the sepsis group, 14 patients showed signs of intracranial hemorrhage during the hospital stay of which four expired and six showed signs of ventricular dilatation during follow-up. These patients had significantly higher CBFV compared to those who survived. Assessment of CBFV at early hours of birth can be adopted as an additional bedside, non-invasive investigation with immediate diagnostic and late prognostic significance.