Welcome to the 9th EAPS Congress Programme Scheduling

Abstract Body

Despite important regulatory initiatives, efforts (and successes) by pharma and academia, and advances in both basic science and pediatric clinical trials, there is (still) a lack of available medicines with an appropriate drug label for neonates, children and adolescents. Pediatricians and other health care professionals have the professional duty to choose medicines that are in the best interest of their individual patient, regardless if these are on-label or off-label. An important reason for use of off-label medicines is to improve access to (innovative) treatments or to address unmet medical needs and patient preferences, especially when no other options are available. The professional setting (both legal and paralegal) does not limit the right of prescribers to prescribe on-label medicines only, as this would in many cases lead to a conflict of professional duties. Therefore, in practice, at the national level, off-label use of medicines is often ethically and legally ‘accepted’ under restrictions. There is consensus that off-label is considered to be rational and clinically appropriate if the benefits outweigh the risks. However, guidance on how to assess this balance is limited.

During this presentation, an overview of challenges related to off-label drug use will be given and practical approaches to prescribing off-label medicines to children, including dose selection, will be offered.

Background and Aims

Background: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications.

Methods

Methods: This prospective, observational study recruited patients up to 60 weeks’ postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events.

Results

Results: Infants (n 5609) born at mean (standard deviation [SD]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm)

underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of

cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2 <85%). Postmenstrual age

influenced the incidence and thresholds for intervention. Risk of critical events was increased by prior neonatal medical

conditions, congenital anomalies, or both (relative risk [RR] 1.16; 95% confidence interval [CI], 1.04e1.28) and in those

requiring preoperative intensive support (RR 1.27; 95% CI, 1.15e1.41). Additional complications occurred in 16.3% of

patients by 30 days, and overall 90-day mortality was 3.2% (95% CI, 2.7e3.7%). Co-occurrence of intraoperative hypotension,

hypoxaemia, and anaemia was associated with increased risk of morbidity (RR 3.56; 95% CI, 1.64e7.71) and

mortality (RR 19.80; 95% CI, 5.87e66.7).

Conclusions

Conclusions: Variability in physiological thresholds that triggered an intervention, and the impact of poor tissue

oxygenation on patient’s outcome, highlight the need for more standardised perioperative management guidelines for

neonates and infants.

Background and Aims

Background: Magnesium is essential for the energy production and synthesis of DNA, RNA, and proteins. Hypomagnesemia is associated with the increased release of endothelin and proinflammatory cytokines and increased pyroptosis as Mg inhibits the non-canonical pyroptosis. This is a strong association of hypomagnesemia and mortality due to the upregulation of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6).

Objectives – Primary objective is to assess magnesium levels in patients with severe pneumonia and its association with clinical severity and adverse outcomes. The secondary objective is to study the association of serum calcium and phosphorus levels controlling for nutritional status.

Methods

110 patients admitted with severe community-acquired pneumonia were enrolled. Their blood samples were collected and assessed for serum magnesium using the selectra PRO M autoanalyzer. Data collected was used for 2 prospective scoring systems modified PIRO score and PRESS scoring system. ROC was generated for respective scores. Logistic regression analysis was done for determining the determinants of mortality. After obtaining results of serum magnesium, the recruited patients were divided into two groups, group A (low serum magnesium<1.7mg/dl), and group B (serum magnesium level ≥ 1.7mg/dl), for further evaluation.

Results

Hypomagnesemia (<1.7mg/dl) was found to be present in 52 /110 (47.3%). Vaccination status (OR 4.17), longer duration of hospital stays (>30 days) (OR-1.9), poor feeding (OR-3.03), arterial saturation <90%, presence of danger signs (OR-4.57) were significantly associated (p < 0.05) with hypomagnesemia. The mean PRESS score of patients in group A was 3.52±1.15 and patients of group B were 2.66±1.25. The mean PIRO score of patients of group A was 4.38±2.43 and group B 2.55±1.97. The adverse outcomes mechanical ventilation (61.5%), prolonged use of oxygen >14days (63.5%), persistent of fever (65.4%), appearance of danger signs (42.3%) shock (36.5%), mortality (58%) was higher in patients of group A and statistically significant (<0.001). A simple linear regression was calculated to predict CRP based on serum magnesium.

CRP increased by 31.15mg/dl for each mg/dl dec in serum magnesium.

The AUC for the modified PIRO score for prediction of mortality was 0.816 and for the modified PIRO score was 0.917.

AUC for magnesium was 0.473.

There was a strong negative correlation between magnesium levels and adverse outcomes as seen by Pearson correlation.

We found that controlling for hypoxia, hypomagnesemia is an independent risk factor for mortality in patients with severe pneumonia. There was a strong positive correlation between magnesium and serum calcium and phosphorus as seen by the Pearson correlation.

Conclusions

- Serum magnesium levels were decreased in 47.3% of patients with severe pneumonia (52/110). This is a strong association of hypomagnesemia with mortality according to our study and hypomagnesemia is an independent indicator of mortality, hence serum magnesium should be screened regularly in the PICU and should be supplemented to patients with prolonged mechanical ventilation.