A meta-analysis was performed to evaluate the accuracy of determination of procalcitonin (PCT) and C-reactive protein (CRP) levels for the diagnosis of bacterial infection. The analysis included published studies that evaluated these markers for the diagnosis of bacterial infections in hospitalized patients. PCT level was more sensitive (88% [95% confidence interval [CI], 80%-93%] vs. 75% [95% CI, 62%-84%]) and more specific (81% [95% CI, 67%-90%] vs. 67% [95% CI, 56%-77%]) than CRP level for differentiating bacterial from noninfective causes of inflammation. The Q value for PCT markers was higher (0.82 vs. 0.73). The sensitivity for differentiating bacterial from viral infections was also higher for PCT markers (92% [95% CI, 86%-95%] vs. 86% [95% CI, 65%-95%]); the specificities were comparable (73% [95% CI, 42%-91%] vs. 70% [95% CI, 19%-96%]). The Q value was higher for PCT markers (0.89 vs. 0.83). PCT markers also had a higher positive likelihood ratio and lower negative likelihood ratio than did CRP markers in both groups. On the basis of this analysis, the diagnostic accuracy of PCT markers was higher than that of CRP markers among patients hospitalized for suspected bacterial infections.

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Serum Procalcitonin and C-Reactive Protein Levels as Markers of Bacterial Infection: A Systematic Review and Meta-analysis

Assessment of cerebral autoregulation is an important adjunct to measurement of cerebral blood flow for diagnosis, monitoring or prognosis of cerebrovascular disease. The most common approach tests the effects of changes in mean arterial blood pressure on cerebral blood flow, known as pressure autoregulation. A 'gold standard' for this purpose is not available and the literature shows considerable disparity of methods and criteria. This is understandable because cerebral autoregulation is more a concept rather than a physically measurable entity. Static methods utilize steady-state values to test for changes in cerebral blood flow (or velocity) when mean arterial pressure is changed significantly. This is usually achieved with the use of drugs, shifts in blood volume or by observing spontaneous changes. The long time interval between measurements is a particular concern in many of the studies reviewed. Parallel changes in other critical variables, such as pCO2, haematocrit, brain activation and sympathetic tone, are rarely controlled for. Proposed indices of static autoregulation are based on changes in cerebrovascular resistance, on parameters of the linear regression of flow/velocity versus pressure changes, or only on the absolute changes in flow. The limitations of studies which assess patient groups rather than individual cases are highlighted. Newer methods of dynamic assessment are based on transient changes in cerebral blood flow (or velocity) induced by the deflation of thigh cuffs, Valsalva manoeuvres, tilting and induced or spontaneous oscillations in mean arterial blood pressure. Dynamic testing overcomes several limitations of static methods but it is not clear whether the two approaches are interchangeable. Classification of autoregulation performance using dynamic methods has been based on mathematical modelling, coherent averaging, transfer function analysis, crosscorrelation function or impulse response analysis. More research on reproducibility and inter-method comparisons is urgently needed, particularly involving the assessment of pressure autoregulation in individuals rather than patient groups.

https://iopscience.iop.org/article/10.1088/0967-3334/19/3/001/pdf

Assessment of cerebral pressure autoregulation in humans - a review of measurement methods

The body of literature concerning studies of the applications of CRP measurement in the pediatric population continues to grow. Based on current data serial CRP measurements appear to be most useful for monitoring patient response to therapy after the primary diagnosis of invasive infectious or inflammatory diseases, for monitoring patients after major surgical procedures and those with serious burns. Monitoring CRP over time may be used to assess for recrudescent disease, a secondary process or ineffective therapy. In addition CRP appears to be suited to most applications for which the ESR is used but offers many advantages. At present there are no objective outcome-based clinical trial data to justify using CRP values alone, whether elevated or normal, as a basis for management decisions regarding instituting or withholding antimicrobial therapy, or its early discontinuance for patients suspected of having neonatal sepsis, meningitis, bacteremia or pneumonia, regardless of immune status. In addition, because of significant inconsistencies among studies for which CRP has been applied to differential diagnosis of bacterial vs. viral diseases, including meningitis, acute otitis media and lower respiratory tract infection, we cannot recommend it for this purpose. Data do not support a role for CRP in differential diagnosis of acute appendicitis or for localizing urinary tract infections.

Clinical applications of C-reactive protein in pediatrics.

Effects of indomethacin on cerebral haemodynamics in very preterm infants

Mean arterial blood pressure changes in premature infants and those at risk for intraventricular hemorrhage.

Cerebral artery Doppler ultrasound recordings, and intra-arterial pressure measurements have been made from 27 very low birth weight infants during the first week of life. These data were used to calculate Pourcelot's resistance index (RI), mean blood flow velocity, and resistance-area product (RAP), in both the anterior and middle cerebral arteries. There was a good degree of correlation between recordings from different sites on the same occasion, but absolute values were site dependent. Over the first three days of life there was a significant increase in blood flow velocity in each of the vessels, and a significant fall in RI and RAP.

Resistance index, blood flow velocity, and resistance-area product in the cerebral arteries of very low birth weight infants during the first week of life

Little is known about the vasoactivity of cerebral arterioles in extremely premature infants. We have assessed the effects of a small rise in PaCO2 of 1 kPa (7.5 mm Hg) on cerebral blood flow velocity measured by duplex Doppler ultrasound. Nineteen mechanically ventilated infants of 33 wk gestational age or less in whom direct arterial blood pressure monitoring was available, were studied on 45 occasions. There was a close relationship between increasing PaCO2 and increasing cerebral blood flow velocity (p < 0.005) but on seven of 45 occasions the cerebral blood flow velocity fell with rising PaCO2. There was a 44% (median value) rise in cerebral blood flow velocity per 1 kPa rise in PaCO2 (5.9%/l mm Hg) in 21 infants tested within 24 h of birth and this increased to a 53% (median value) rise (7%/l mm Hg) in 20 infants tested after 24 h (p < 0.001). Eleven infants had paired studies, the first within 24 h and a second at a median age of 48 h. There was a statistically significant increase in percentage reactivity when the later group was compared to those tested within 24 h (p < 0.001). Carbon dioxide reactivity was also assessed before and after indomethacin infusion (0.2 mg/kg) on four occasions and there was a reduction in reactivity from a median value of 144 to 49.5%, 10 min after indomethacin. The extremely immature, ill infant is less sensitive to a small change in PaCO2 within 24 h of birth and after indomethacin infusion. We speculate that this may be related to a state of relative arteriolar vasoconstriction compared with infants 24 h or more after birth and those not influenced by the vasoconstrictor properties of indomethacin.

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Carbon dioxide reactivity of the cerebral circulation in extremely premature infants: effects of postnatal age and indomethacin.

Intra-arterial blood pressure measurements recorded during the first week of life in 32 stable very low birth weight infants (20 of birth weight up to 1250 g and 12 with birth weight 1251-1500 g) were reviewed. None of the infants received inotropic drugs or were given infusions of colloids to manipulate the blood pressure during the periods from which the recordings were taken. The mean systolic, mean and diastolic blood pressure measurements for infants of birth weight greater than 1250 g were significantly higher than those recorded in the infants of birth weight of up to 1250 g (figure 1). The mean blood pressure (calculated by adding one third of the pulse pressure to the diastolic pressure) in the larger infants showed a significant increase with increasing postnatal age, but this increase was not apparent in the smaller infants (figure 2). Figure 3 shows the range of systolic, mean and diastolic blood pressure values that were recorded. The mean values were remarkably constant with diastolic blood pressure varying between 31 and 34 mmHg, mean blood pressure between 35 mmHg and 40 mmHg, and systolic blood pressure between 46 mmHg and 52 mmHg. Intra-arterial lines provide a convenient and accurate route for blood pressure monitoring. It is important that a normal range of blood pressure values in the very low birth weight infant is established so that hypotension, with the potential risk of cerebral ischemia, can be avoided.

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Blood pressure measurements in very low birth weight infants over the first week of life.

C. reactive protein (CRP) estimations were performed prospectively on 30 consecutive admissions of very low birth weight infants to a Regional neonatal intensive care unit. The samples were analysed by a recently described, rapid intralipid agglutination assay and by a reference turbidimetric technique. Two hundred and ninety samples were assayed by both techniques. The intralipid agglutination was positive on two occasions when the reference method found normal levels. No false negative reactions occurred. Bacterial micro-organisms were isolated on 32 occasions but 19 of the organisms were considered to represent bacterial colonisation or contamination. The CRP remained negative in 17 cases. There were 13 episodes of clinical deterioration associated with positive bacterial cultures. In each of the six infants with severe systemic infections (septicaemia (4), meningitis (1), and osteomyelitis (1)), the levels were raised. In five of these infants the CRP was elevated before, or at the time of, the clinical deterioration. The CRP remained normal during seven (54%) of the culture positive events. We believe that the CRP estimations provide additional information in the evaluation of the infant with suspected sepsis. Serial measurements are helpful in distinguishing bacterial contamination from invasive infection but are not helpful in predicting infection during the pre-clinical phase. The intralipid agglutination technique is a rapid and reliable test and could be performed on the neonatal unit outside normal laboratory hours.

David Barry Shortland

Papers

Resistance index, blood flow velocity, and resistance-area product in the cerebral arteries of very low birth weight infants during the first week of life

Carbon dioxide reactivity of the cerebral circulation in extremely premature infants: effects of postnatal age and indomethacin.

Blood pressure measurements in very low birth weight infants over the first week of life.

Evaluation of C. reactive protein values in neonatal sepsis.