Welcome to the ESPNIC Xperience Programme Scheduling
The meeting will run on Central European Summer Time
O-GLCNAC STIMULATION IS BENEFICIAL IN SEPSIS IN THE YOUNG, INVOLVEMENT OF THE ATP-CITRATE LYASE
Abstract
Background and Aims
O-GlcNAc is a post-translational modification involved in cell survival and metabolism. We have shown that O-GlcNAc stimulation at the early phase of septic shock is beneficial in adult rats. The young population, particularly at risk of severe complication during sepsis, is rarely studied. The purpose of the project is to evaluate if O-GlcNAc stimulation could improve sepsis outcomes in young.
Methods
Endotoxemic shock was induced in 28 days old rats with an intravenous injection of saline (CTRL) or LPS (O111:B4, 20mg.kg-1). One hour after LPS injection rats were randomly assigned to no therapy (LPS), fluidotherapy (saline, 10ml.kg-1 - LPS+R) ± NButGT (10 mg.kg-1 - NButGT) to increase O-GlcNAc levels. Physiological functions and plasmatic markers were evaluated 2 hours later, as well as mortality over 36 hours. Untargeted mass spectrometry was performed to identify cardiac O-GlcNAcylated proteins.
Results
LPS induced a shock (mean arterial pressure: CTRL: 67.2±1.9; LPS: 50.7±2.1 mmHg; p<0.05), altered biological parameters (lactates: CTRL: 3.92 ± 0.26; LPS: 6.42 ± 0.45 mmol.l-1; p<0.05). LPS+R had no beneficial effect while NButGT improves mean arterial pressure (NButGT: 72.2±4.0 mmHg; p<0.05) and median time of survival (p<0.05). Mass spectrometry identifies the ATP-citrate lyase as the only protein less O-GlcNAcylated in the NButGT group; interestingly its phosphorylation in position 447 and 451 is not impacted, suggesting that O-GlcNAcylation does not impact these phosphorylation sites.
Conclusions
O-GlcNAc stimulation acutely improves outcome in young septic shock rat. The impact of O-GlcNAcylation on the ATP-citrate lyase is a potential issue to decipher the role of this protein during sepsis.
IMPACT OF MULTIDRUG-RESISTANT BACTERIA IN PAEDIATRIC SEPSIS IN THE ENVIN-HELICS NATIONAL REGISTRY
Abstract
Background and Aims
The emergence of multidrug-resistant (MDR) microorganisms is a growing concern in paediatric critically ill patients. The aim of this study is to describe the profile of MDR bacteria in critically ill children with sepsis and assess its impact on morbidity and mortality.
Methods
Restrospective analysis of critically ill children with sepsis included in the national multi-center registry ENVIN-HELICS between 2013-2017. Variables regarding demographic and microbiology data, risk factors for infection and antibiotic treatment were recorded. The primary outcome was in-hospital mortality and the secondary outcomes were length of hospital and PICU stay.
Results
346 patients with a median of age of 11 months (ICR 0-250 months) and PRIMS III score of 7 (ICR 0-40) were included. In-hospital mortality rate was 13.3%. MDR bacteria were isolated in 112 patients (32.4%) from which 85.3% were Gram negative. 48% of these infections were acquired during PICU admission. Risk factors for MDR bacterial sepsis included antibiotic treatment prior to admission, parenteral nutrition, inmunosupression, kidney failure and malnutrition. Higher mortality was reported in patients positive for MDR Pseudomonas (30%) and MRSA (33%). Patients with MDR bacterial sepsis had longer PICU (OR 1.2 95% CI 1.01-1.3) and hospital stay (OR 1.5 95% CI 1.2-2). No differences were found between hospital and community acquired sepsis.
Conclusions
Management of MDR bacterial sepsis in PICU patients can be challenging due to its high morbidity and mortality. Prevention strategies and implementation of antimicrobial stewardship programs are necessary to improve outcomes in critically ill children with sepsis.
DOES CPAP INCREASE OR DECREASE THE RISK OF SELF-INFLICTED LUNG INJURY IN INFANT WITH BRONCHIOLITIS?
Abstract
Background and Aims
Potential adverse impact of spontaneous effort in patient with lung injury is an emerging concept in adults described as patient self-inflicted lung injury (p-SILI). High spontaneous effort may participate in the alveolar injury in infant with severe bronchiolitis. We hypothesize that nCPAP may prevent the risk of p-SILI by decreasing the lung stress.
Methods
We conducted a secondary analysis (ethics approval CE SRLF 20-19) of a prospective physiological study including infants with severe bronchiolitis < 3 months. Esophageal (Peso), gastric (Pga), and airway (Paw) pressures, electrical activity of the diaphragm (Edi), and Flow were recorded in spontaneous breathing (SB) and in n-CPAP 7 cmH2O, applied for 1 hour. Inspiratory transpulmonary pressure (TPP) was estimated as Paw-Peso at the minimal Peso Swing.
Results
Twelve children (median [IQR] age 30 [22-49] days, mWCAS 4.5 [4.5-5.0]) were included. Delta Edi and Peso swing were significantly lower in CPAP than in SB (Table 1). The TPP was not different between the 2 modes. The change in TPP was negatively correlated with TPP in SB (r=-0.72, p=0.002), indicating a decrease in TPP in infants with higher effort at baseline (Fig.1)
| Table 1 | SB | nCPAP | P* |
| Respiratory, rate /min | 65 [59-79] | 66 [51-85] | 0.81 |
| Delta Edi, µV | 27 [33-33] | 19 [16 - 25] | 0.002 |
| Swing Peso, cmH2O | 19 [16-30] | 16 [10-18] | 0.003 |
| Transpulmonary pressure, cmH2O | 12 [10-20] | 16 [12-18] | 0.43 |
Conclusions
In infants with severe bronchiolitis, the application of a nCPAP may help to decrease the risk of p-SILI but only in infants with high TPP in spontaneous breathing.
COMPARISON OF SEPSIS PROGNOSTIC SCORES ACCURACY IN PREDICTING OUTCOMES IN CRITICALLY ILL CHILDREN WITH SEPSIS ADMITTED TO THE PICU: A SINGLE TERTIARY CENTER 10-YEAR EXPERIENCE
Abstract
Background and Aims
Current sepsis definition in pediatrics, developed in 2005, does not include the concept of organ dysfunction. In adults, Sepsis-3 consensus (2016), defined sepsis as life-threatening organ dysfunction, removing the concepts of SIRS criteria and severe sepsis. SOFA score in adults demonstrated a good prognostic accuracy at discriminating mortality among patients with sepsis. Those definitions were not validated in pediatrics and the most appropriate method to identify organ-dysfunction remains still to be established in this population. We aimed to compare the performance of several prognostic scores in predicting outcomes of critically ill children with sepsis admitted to the PICU.
Methods
Single-center, retrospective cohort study in children with sepsis visiting the PED and admitted to the PICU of a tertiary-level pediatric hospital. Multiple prognostic scores (i.e. SOFA scores, PELOD-2) calculated in the first day of admission were compared to SIRS and severe sepsis criteria by AUROC analysis. Outcomes: PICU mortality (primary), duration of mechanical ventilation (MV) (secondary).
Results
Of 60 patients with sepsis, 6.7% patients died, 43.3% experienced prolonged LOS, 35% experienced prolonged invasive MV. The discrimination of mortality was significantly higher for PELOD-2 (AUROC 0.924), Schlapbach (AUROC 0.929) and Shime (AUROC 0.882) version of SOFA than for SIRS criteria and severe sepsis. Prolonged duration of invasive MV either was better predicted by PELOD-2 than SIRS criteria and severe sepsis.
Conclusions
Organ-dysfunction scores in the first day of admission performed better in predicting outcomes than SIRS criteria and severe sepsis. PELOD-2 was the organ-dysfunction score that performed better both for primary and secondary outcomes.
PIPERACILLIN-TAZOBACTAM PHARMACOKINETICS IN CRITICALLY ILL CHILDREN
Abstract
Background and Aims
Piperacillin-tazobactam is a commonly used antibiotic in critically ill children. Standard dosing could fail to achieve adequate plasma concentrations in ICU patients in which higher or even a 100% of target free time above the MIC (fT>MIC) is desirable. Besides, there is no data about piperacillin pharmacokinetics in children with CRRT.
Methods
Piperacillin pharmacokinetics in critically ill children without (receiving 100 mg/kg/8h bolus) and with CRRT (receiving 100 mg/kg/12h bolus) were studied. Blood or prefilter, postfilter and ultrafiltrate samples were drawn. Data were analysed by a population approach using NONMEM 7.4. The probability of target fT>MIC during the entire dosing interval was estimated by simulation of different intermittent and continuous infusions.
Results
32 patients were included: 19 without CRRT and 13 with CRRT (median age of 12 months-of-age, 10 kg of weight). Pharmacokinetics data are presented in Figure 1. Only 15.6% of patients without TDEC achieved 95% fT >MIC(8) and 12.5% of them 50% fT>4xMIC(32). 61% of children with CRRT achieved 95% fT >MIC(8) and 54% of them 50% fT>4xMIC(32). Simulated dosing interval effects on fT>MIC is shown in Figure 2.
Conclusions
The standard dose of 100 mg/kg/8h bolus could be insufficient to achieve optimal piperacillin exposures in a significant proportion of critically ill children. Extended or continuous infusions may be considered. The 100 mg/kg/12h dose for CRRT can be insufficient in achieving optimal free piperacillin concentrations, a dose of 100 mg/kg/8h may be considered. An individualized dosing approach needs to be adopted in order to maximize antibiotic efficacy.
EMPOWERMENT OF PARENTS IN THE INTENSIVE CARE STUDY: MULTI-CENTRE STUDY IN JAPANESE PICUS
Abstract
Background and Aims
To validate the EMpowerment of Parents in THe Intensive Care 30 (EMPATHIC-30) questionnaire in Japanese PICUs and to identify potential factors for family-centred care satisfaction.
Methods
An observational study was conducted in 4 PICUs. Reliability was measured by Cronbach’s α and congruent validity was tested with overall satisfaction-with-care scales by correlation analysis. Multivariate linear regression modeling was conducted to identify factors related to each domain of the Japanese EMPATHIC-30. This study was approved by all Institutional Review Boards and written, informed consent was obtained by parents or legal guardians.
Results
From April 2020 to February 2021, a total of 163 parents (average age 31.9 ± 5.4 years; 81% were mothers) participated. During their PICU stay, 46% of children received mechanical ventilation. The domains of the Japanese EMPATHIC-30 showed high reliability (α = 0.87 to 0.97) and were highly correlated with overall satisfaction with nurses (r = 0.75) and doctors (r = 0.76). Professional attitude and parental participation domain levels were also highly correlated (r = 0.91). Multivariate modeling found that elective admission, using mechanical ventilation, and parents whose partners have ICU experience had higher satisfaction scores in all five categories (p<0.05) while Buddhists assigned higher satisfaction scores in categories of care and cure (p=0.03).
Conclusions
We showed the high accuracy of the Japanese EMPATHIC-30 questionnaire and factors related to family-centred care satisfaction in Japanese PICUs. The results reveal general and cultural differences in factors and the actual condition of family care satisfaction across Asian and European countries.