Fauzia Paize

Peripheral haemodynamics in newborns: Best practice guidelines

Peripheral haemodynamics refers to blood flow, which determines oxygen and nutrient delivery to the tissues. Peripheral blood flow is affected by vascular resistance and blood pressure, which in turn varies with cardiac function. Arterial oxygen content depends on the blood haemoglobin concentration (Hb) and arterial pO2; tissue oxygen delivery depends on the position of the oxygen-dissociation curve, which is determined by temperature and the amount of adult or fetal haemoglobin. Methods available to study tissue perfusion include near-infrared spectroscopy, Doppler flowmetry, orthogonal polarisation spectral imaging and the peripheral perfusion index. Cardiac function, blood gases, Hb, and peripheral temperature all affect blood flow and oxygen extraction. Blood pressure appears to be less important. Other factors likely to play a role are the administration of vasoactive medications and ventilation strategies, which affect blood gases and cardiac output by changing the intrathoracic pressure.

Cause of Death in Infants of Women with Pregestational Diabetes Mellitus and the Relationship with Glycemic Control

Abstract Background: Perinatal mortality remains high among infants of mothers with type 1 and type 2 diabetes mellitus. Although high glucose levels have been implicated, the mechanism is not well understood. Aims: 1) to identify the causes of stillbirth and neonatal death in infants of women with type 1 and type 2 diabetes; 2) to determine whether the causes of perinatal mortality are the same for women with type 1 and type 2 diabetes; and 3) to ascertain the relationship between perinatal mortality and maternal glycemic control. Materials and methods: the case notes of women with type 1 and type 2 diabetes mellitus who had a stillbirth or neonatal death were identified and examined by 2 reviewers independently. Results: Ninety-three perinatal deaths were identified (59 women with type 1 diabetes; 34 women with type 2 diabetes). There were 73 stillbirths, 12 were early neonatal deaths, and 8 were late neonatal deaths. Eighteen deaths were attributed to congenital anomalies, 64 to antepartum asphyxia, 4 to intrapartum asphyxia, 3 to postnatal hyaline membrane disease, 2 to postnatal infection, 1 was unclassifiable, and 1 case had no details available. Median postmenstrual age at death was 34 weeks for both women with type 1 and type 2 diabetes. Congenital anomalies were less common in women with type 1 dia-betes than those with type 2 diabetes (rate ratio, 0.37 [95% confidence interval, 0.15–0.95]). The relationship between preconceptional and maximal maternal glycosylated hemoglobin (HbA1c) concentrations and birth weight was curvilinear: at low HbA1c levels, the fetal weight was normal; when HbA1c levels were moderately raised, there was macrosomia; very high HbA1c levels were associated with severe intrauterine growth restriction. Conclusion: We describe a relationship between HbA1c and fetal weight. We consider that this provides evidence that hyperglycemia not only causes fetal macrosomia but also an angiopathy affecting the utero-placental blood vessels and consequent fetal hypoxia. These observations provide further evidence that good pre- and periconceptional glycemic control is likely to be of great importance in improving the outcome of pregnancies of women with diabetes.

Estimating Individual-Level Risk in Spatial Epidemiology Using Spatially Aggregated Information on the Population at Risk

We propose a novel alternative to case-control sampling for the estimation of individual-level risk in spatial epidemiology. Our approach uses weighted estimating equations to estimate regression parameters in the intensity function of an inhomogeneous spatial point process, when information on risk-factors is available at the individual level for cases, but only at a spatially aggregated level for the population at risk. We develop data-driven methods to select the weights used in the estimating equations and show through simulation that the choice of weights can have a major impact on efficiency of estimation. We develop a formal test to detect non-Poisson behavior in the underlying point process and assess the performance of the test using simulations of Poisson and Poisson cluster point processes. We apply our methods to data on the spatial distribution of childhood meningococcal disease cases in Merseyside, U.K. between 1981 and 2007.

Meningococcal Disease in Children in Merseyside, England: A 31 Year Descriptive Study

Meningococcal disease (MCD) is the leading infectious cause of death in early childhood in the United Kingdom, making it a public health priority. MCD most commonly presents as meningococcal meningitis (MM), septicaemia (MS), or as a combination of the two syndromes (MM/MS). We describe the changing epidemiology and clinical presentation of MCD, and explore associations with socioeconomic status and other risk factors. A hospital-based study of children admitted to a tertiary childrens centre, Alder Hey Childrens Foundation Trust, with MCD, was undertaken between 1977 to 2007 (n = 1157). Demographics, clinical presentations, microbiological confirmation and measures of deprivation were described. The majority of cases occurred in the 1–4 year age group and there was a dramatic fall in serogroup C cases observed with the introduction of the meningococcal C conjugate (MCC) vaccine. The proportion of MS cases increased over the study period, from 11% in the first quarter to 35% in the final quarter. Presentation with MS (compared to MM) and serogroup C disease (compared to serogroup B) were demonstrated to be independent risk factors for mortality, with odds ratios of 3.5 (95% CI 1.18 to 10.08) and 2.18 (95% CI 1.26 to 3.80) respectively. Cases admitted to Alder Hey were from a relatively more deprived population (mean Townsend score 1.25, 95% CI 1.09 to 1.41) than the Merseyside reference population. Our findings represent one of the largest single-centre studies of MCD. The presentation of MS is confirmed to be a risk factor of mortality from MCD. Our study supports the association between social deprivation and MCD.

Improvements in the outcome of children with meningococcal disease

Recent years have seen a marked reduction in the mortality of children with meningococcal disease in paediatric intensive care units (PICU); the reasons for this improvement are multifactorial. The mortality rates for critically ill children overall have improved and reasons for this are probably increased centralisation of PICU services and that fewer critically ill children are now looked after on adult units. Specific treatment pathways for sepsis have improved with the publication of clinical guidelines for children and initiatives such as the Surviving Sepsis Campaign. There is a continuing need to focus on the care delivered to children before reaching PICU and to minimise the morbidity suffered by survivors of this disease.

Diagnostic efficacy of activated partial thromboplastin time waveform and procalcitonin analysis in pediatric meningococcal sepsis.

Objective: A biphasic activated partial thromboplastin time waveform predicts sepsis and disseminated intravascular coagulation in adults. This has not been previously investigated in children. Our aim is to ascertain whether there are changes in the activated partial thromboplastin time waveform in children with meningococcal disease and to compare its diagnostic use with procalcitonin. Setting: Alder Hey Childrens National Health Service Foundation Trust, Liverpool, UK. Patients: Thirty-six children admitted to the hospital for the treatment of suspected meningococcal disease had activated partial thromboplastin time waveform and procalcitonin analysis performed at admission. The light transmittance level at 18 secs was used to quantitate the waveform. Severity of disease was assessed using the Glasgow Meningococcal Septicaemia Prognostic Score, Pediatric Risk of Mortality III score, and the Pediatric Logistic Organ Dysfunction score. Measurements and Main Results: Twenty-four children had proven meningococcal disease, 12 had a presumed viral illness, and 20 control subjects were recruited. Transmittance level at 18 secs was lower in children with meningococcal disease and those with a viral illness (p < .0001) and control subjects (p < .0005). Sensitivity and specificity was 0.91 and 0.96 for transmittance level at 18 secs and 0.92 and 1 for procalcitonin in identifying meningococcal disease. There was a significant difference in procalcitonin between children with meningococcal disease and those with a viral illness and control subjects (p < .0005). A negative correlation was found between transmittance level at 18 secs and length of hospital stay (p < .0001), C-reactive protein (p < .0001), procalcitonin (p < .0001), Glasgow Meningococcal Septicaemia Prognostic Score (p < .01), Pediatric Risk of Mortality III score (p < .0001), and Pediatric Logistic Organ Dysfunction score score (p < .0001). Conclusion: The activated partial thromboplastin time waveform is abnormal in children with meningococcal disease and may be a useful adjunct in the diagnosis and management of sepsis in children.

Diastolic dysfunction and N-terminal pro-brain natriuretic peptide in children with meningococcal sepsis.

Dear Editor, Myocardial systolic dysfunction is an important problem in children with severe meningococcal disease (MCD) but diastolic function has not been assessed. N-Terminal pro-B-type natriuretic peptide (NT-ProBNP) is released in response to myocyte stretch and is elevated in children with sepsis [1, 2]. We conducted a prospective observational study of children with confirmed MCD between January 2007 and April 2008. Plasma samples were taken at admission and sequentially for estimation of NT-ProBNP. Transthoracic echocardiography utilising tissue Doppler imaging (TDI) was performed whenever blood sampling was carried out. To account for children presenting to PICU at different points in their illness, multiple linear regression analysis was used to assess the independent predictive value of the NT-ProBNP measurement for E/Ea. Twenty ventilated patients, with a median age of 2.5 (IQR 0.96– 4.4) years, were recruited and all survived. Seven had abnormal diastolic function at admission with low Ea velocity. These seven children had an E/Ea ratio above 10, indicating an abnormally raised LV filling pressure. A significant difference between the admission and pre-extubation values was found for the Ea velocity and the E/Ea ratio (p \ 0.05). Median admission NT-proBNP levels in the MCD patients were 2,783.2 fmol/ml (IQR 2,163.7– 5,657.5), compared with 381.5 fmol/ ml (IQR 184.2–511.4) in ten agematched children with a febrile viral illness. There was a negative correlation between admission NTProBNP and Ea value (r = -0.57, p \ 0.05). This was no longer significant 24 h after admission. Multiple linear regression analysis was used to assess the independent ability of NT-ProBNP to predict the E/Ea ratio after adjustment for the duration of illness, including duration of rash prior to PICU admission and duration of ventilation prior to admission to PICU. The results show that NT-ProBNP levels predict LV filling pressure, as assessed by the E/ Ea ratio, irrespective of the stage of illness at the time of admission with an increase of 1,000 fmol/ml in admission BNP increasing the E/Ea ratio by around 1.4 (Table 1). These are the first data to demonstrate diastolic dysfunction and elevated levels of NT-ProBNP in children with severe MCD. We also show an association between the two although the relationship is not necessarily causative. Resuscitation volume could cause elevated filling pressures and hence BNP release, although Roch et al. [3] found that fluid loading was not a significant predictor of a high NT-ProBNP level in a multivariate analysis. An increase in systemic vascular resistance by inotropic support may also contribute to diastolic dysfunction. The method of resuscitation for children not responding to conventional treatment may need to be reconsidered in light of these findings. Agents such as milrinone or levosimendan could reduce excess LV filling pressures in such circumstances by means of their vasodilatory effects [4, 5]. Fried and colleagues compared NT-Pro BNP levels in children with sepsis and those with a febrile viral illness. Higher levels were found in those with sepsis [1], raising the possibility that NT-ProBNP is released as a result of an inflammatory process alone. Larger studies in a similar population are needed to confirm these findings.

Personal practiceWhich inotrope

Critically ill children with shock frequently require the administration of inotropic and vasoactive agents. The appropriate choice of inotropic agent in these children forms only part of their overall management. In most cases children requiring inotropes should already have received aggressive fluid resuscitation and prompt tracheal intubation and mechanical ventilation will be indicated in the majority of cases. The first-line inotrope for children with shock and hypotension is dopamine. Dopamine should be administered centrally or via the intraosseous route. In patients resistant to fluid therapy and dopamine secondary agents should be administered; adrenaline for ‘cold shock’ and noradrenaline for ‘warm shock’. Simple clinical and therapeutic endpoints should be used as surrogate markers of cardiac output in order to monitor progress and response to treatment. Children requiring inotropic or vasoactive agents should be reassessed frequently as the cardiovascular profile of children with shock frequently changes particularly during the early phases of their illness.