Early hyperlactataemia in critically ill children.

OBJECTIVE: To examine the relationships between early hyperlactataemia, acidosis, organ failure, and mortality in children admitted to intensive care. DESIGN: Prospective observational study. Children with lactate levels > 2 mmol/l were eligible for enrolment. Post-operative patients and those with inherited metabolic disease were excluded. Seven hundred and five children admitted to intensive care were screened, and 50 children with hyperlactataemia (incidence 7%), aged 20.3 months (0.1-191) were enrolled and followed up. The Paediatric Risk of Mortality (PRISM) score, Multiorgan System Failure (MOSF) score, length of ICU stay, and outcome were recorded. Data were collected for lactate (mmol/l), pH, and base excess (BE) until 24 h after admission. Data are reported as median (range) and were analysed by the Mann-Whitney, Fisher's Exact, and Kruskal-Wallis tests, and chisquared test for trend. RESULTS: Overall mortality in the screening group was 70/705 (10%). In the study group (n = 50) median PRISM score was 19 (4-49), median MOSF score 2 (1-4), and observed mortality 32/50 (64%). Median duration of ICU stay was 6 days (2-32) in survivors, and median time until death 3 days (0-13) in nonsurvivors. Eleven nonsurvivors (34%) died within 24 h. In the screening group, hyperlactataemia on admission identified mortality with likelihood ratio = 15. In the study group, neither the admission lactate (3.8 vs 4.6 mmol/l, P = 0.27), pH (7.32 vs 7.30, P = 0.6), nor BE (-7.5 vs -8, P = 0.45) differed significantly between survivors and nonsurvivors. Neither the admission nor peak lactate increased with increasing MOSF score (P = 0.5 and 0.54). The median peak lactate level was 5 mmol/l (2-9.3) in survivors compared to 6.8 mmol/l (2.3-22) in nonsurvivors (P = 0.02), and the cumulative average lactate level was 2.4 mmol/l (1-4.9) in survivors, compared to 4.5 mmol/l (1.6-21) in nonsurvivors (P = 0.0003). Persistent hyperlactataemia 24 h after admission identified mortality with likelihood ratio = 7. CONCLUSION: Hyperlactataemia on admission to intensive care is associated with a high mortality in children. Nonsurvivors within this group may be distinguished by the peak lactate level, or by persistent hyperlactataemia after 24 h of treatment.

Altered course of visceral leishmaniasis in mice expressing transgenic I-E molecules.

Previous studies had shown that the outcome of infection with Leishmania donovani was exquisitely sensitive to the influence of the major histocompatibility complex. In this study, we have examined the course of infection in non-obese diabetic (NOD) and NOD-E-3 mice, the latter expressing an I-E molecule as a result of transgenic introduction of the wild-type Ed alpha gene. Introduction of this transgene significantly altered the course of infection allowing for enhanced parasite multiplication in the viscera from day 14 to day 28. This was associated with both a delayed and reduced tissue granulomatous response in NOD-E-3 mice. In vitro, spleen cells from these mice produced equivalent levels of interferon (IFN)-gamma during the early phase of infection but this originated from populations having a different balance of T cells subsets. In NOD mice CD8+ T cells contribute substantially to the total levels of IFN-gamma produced, but in transgenic mice the contribution from this subset is significantly decreased. This is reflected in a reduction in the proportion of Leishmania-specific CD8+ T cells, which could only partially be accounted for by deletion of V beta 5- and V beta 3-expressing CD8+ T cells in NOD-E-3 mice. This study highlights the impact of the introduction of a class II gene product on disease outcome and unexpectedly on the functional potential of CD8+ T cells.

Procalcitonin: a marker of bacteraemia in SIRS.

A number of European studies have documented the ability of procalcitonin (PCT), a novel inflammatory marker, to discriminate patients with sepsis from those with other causes of systemic inflammatory response syndrome (SIRS). The aim of this study was to assess procalcitonin's performance in an Australian intensive care unit (ICU) setting to examine whether it could discriminate between these two conditions. One hundred and twenty-three consecutive adult ICU patients fulfilling criteria for SIRS were enlisted in the study. Over a period of five days, daily serum PCT and C-reactive protein (CRP) levels were measured. At least two sets of cultures were taken of blood, sputum/broncho-alveolar lavage (BAL) and urine. Other cultures were taken as clinically indicated. Questionnaires to ascertain clinical suspicion of sepsis were prospectively answered by the ICU senior registrars. PCT values were ten times higher in patients with positive blood cultures; CRP values were also significantly higher in the bacteraemic patients. Both PCT and CRP had a good ability to discriminate bacteraemia from non-infectious SIRS, with the area under receiver operating characteristics (ROC) curves for PCT being 0.8 and for CRP being 0.82. However neither PCT or CRP was able to discriminate patients with localized sepsis from those without. Utilizing both tests resulted in a more sensitive screen than either one alone, while PCT was a more accurate diagnostic test for bacteraemia than CRP. The PCT value also differed between those who died in hospital and those who survived. Measurement of PCT alone or in combination with CRP can aid discrimination of septicaemia/bacteriemia with associated SIRS from non-infectious SIRS in an Australian ICU setting.