Risk factors for multidrug-resistant bacteria in critically ill children and MDR score development.

Antimicrobial resistance and healthcare-associated infections (HAIs) are major health concerns in the pediatric intensive care unit (PICU). Device-associated HAIs (DA-HAIs) produced by multidrug-resistant (MDR) bacteria are especially worrying, as they can lead to an inappropriate empirical antibiotic therapy, worsened outcomes and increased mortality. The MDR score was designed to enable the prompt identification of patients at high risk of developing an MDR infection. This was a single-center, prospective, observational study, conducted between January 2015 and December 2022, including PICU patients with a microbiologically confirmed DA-HAI. Demographic, clinical characteristics and outcomes were compared between patients with a DA-HAI caused by MDR and non-MDR-associated DA-HAI, and a risk score for multi-resistance was designed. In total, 257 DA-HAI cases were included, 86 (33.46%) caused by an MDR microbe. In the univariate analysis, comorbidity (p = 0.002), previous MDR colonization (p < 0.001), previous surgery (p = 0.018), and previous antibiotic therapy (p = 0.009) were more frequent among MDR-associated DA-HAI (MDR DA-HAI). In addition, days from device insertion to infection and from PICU admission (p < 0.005) to infection were longer in patients with MDR. In the multivariate analysis, previous comorbidity (OR 2.201), previous MDR colonization (OR 5.149), and PICU length of stay longer than 9 days (OR 1.782) were independently associated with MDR-DA-HAI. Using these three independent risk factors for MDR, a risk score was created: the MDR score. Three risk groups were obtained: low risk (0-2 points), intermediate risk (3-7 points), and high risk (8-12 points). Seventy-one patients with MDR-DA-HAI (82.6%) were classified in the intermediate or high-risk group, with a global sensitivity of 82.6%. The specificity in the high-risk group was 91.8%, and 81.0% of patients who were stratified into the low-risk group had non-MDR-associated infections, so they were correctly classified. Conclusions: The MDR score can be a useful tool to stratify patients in risk groups for MDR-DA-HAI. It may help to guide the choice of empirical therapy, leading to early optimization and avoiding delays in establishing appropriate treatment. This study reinforces the importance of stratifying patients based on their individual risk profile for MDR infection.

Quantification of a qualitative sepsis code: laying the foundations for the automation revolution.

To quantify a qualitative screening tool for the early recognition of sepsis in children with fever either visiting the emergency department or already admitted to hospital. Prospective observational study including febrile patients under 18 years of age. Sepsis diagnosis was the main outcome. A multivariable analysis was performed with 4 clinical variables (heart rate, respiratory rate, disability, and poor skin perfusion). The cut-off points, odds ratio, and coefficients of these variables were identified. The quantified tool was then obtained from the coefficients. The area under the curve (AUC) was obtained and internal validation was performed using k-fold cross-validation. Two hundred sixty-six patients were included. The multivariable regression confirmed the independent association of the 4 variables with the outcome. The quantified screening tool yielded an excellent AUC, 0.825 (95%CI 0.772-0.878, p < 0.001), for sepsis prediction.  Conclusion: We successfully quantified a sepsis screening tool, and the resulting model has an excellent discriminatory power. What is Known: • Screening tests have to be based only on clinical variables that needs minimum technological support. • The current Sepsis Code is a qualitative screening tool. What is New: • The current screening tool was quantified using four clinical variables, weighted according to the deviation from normality and differentiated according to the age of the patient. • The resulting model has an excellent discriminatory power in identifying septic patients among febrile pediatric patients.

Infection what else? The usefulness of procalcitonin in children after cardiac surgery.

OBJECTIVES: Procalcitonin is a useful biomarker for predicting bacterial infection after cardiac surgery. However, sometimes procalcitonin rises following cardiac surgery without a confirmation of bacterial infection. The aim was to analyse procalcitonin levels in children without a bacterial infection after cardiac surgery. STUDY DESIGN: This is a prospective, observational study of children <18 years old admitted to the pediatric intensive care unit after cardiac surgery. RESULTS: 1,042 children were included, 996 (95.6%) without a bacterial infection. From them, severe complications occurred in 132 patients (13.3%). Procalcitonin increased differentially depending on the type of complication. Patients who presented a poor outcome (n = 26, 2.6%) had higher procalcitonin values in the postoperative period than the rest of patients (<24 hours: 5.8 ng/mL vs. 0.6 ng/mL; 24-48 hours, 5.1 ng/mL vs. 0.8 ng/mL, and 48-72 hours, 5.3 ng/mL vs. 1.2 ng/mL), but these values remained stable over time (p = 0.732; p = 0.110). The AUC for procalcitonin for predicting poor outcome was 0.876 in the first 24 hours. The cut-off point to predict poor outcome was 2 ng/mL in the first 24 hours (sensitivity 86.9%, specificity 77.3%). Patients with bacterial infection (n = 46) presented higher values of procalcitonin initially, but they decreased in the 48-72 hours period (<24 hours: 4.9 ng/mL; 24-48 hours, 5.8 ng/mL, and 48-72 hours, 4.5 ng/mL). CONCLUSIONS: A procalcitonin value<2 ng/mL may indicate the absence of infection and poor outcome after cardiac surgery. The evolution of the values of this biomarker might help to discern between infection (where procalcitonin will decrease) and poor outcome (where procalcitonin will not decrease).

Weaning from neonatal and pediatric ECMO with stand-by cannula.

The precise moment for weaning a patient off extracorporeal membrane oxygenation (ECMO) is not always easy to establish. Also, mechanical causes may obligate to disconnect the patient from the circuit before the optimal weaning off. In these selected cases, the patient can be disconnected from the circuit and the cannula can be left in place (stand-by cannula) until the patient's stability without ECMO is assured. The aim was to describe our experience with the stand-by cannula. Single-institution, long-term retrospective study in a pediatric tertiary care hospital. Neonatal and pediatric patients who were under ECMO and needed stand-by cannula before definitive de-cannulation were included. During 18 years, 166 children required ECMO. In 31 patients (18.7%), stand-by cannula was performed before the weaning off. Twenty patients (64.5%) were newborn. The main reason for requiring ECMO in these newborn was persistent pulmonary hypertension. Eleven patients were pediatric and their main cause for requiring ECMO was cardiogenic shock (six patients, 54.4%). The reasons for requiring stand-by cannula were the uncertainty of a successful weaning off in 17 patients (54.8%), to undergo surgery in 10 patients (32.3%) and to replace the circuit in four cases (12.9%). The median duration of stand-by cannula was 12 h (IQR 6-24). Heparinized saline serum was the main maintenance perfusion (28 patients, 90.3%). Three patients needed to restart support with ECMO. Only one mechanical complication was detected. Stand-by cannula is a safe technique, which allows performing a quick re-entrance on ECMO if the weaning off fails.

The different manifestations of COVID-19 in adults and children: a cohort study in an intensive care unit.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has collapsed health systems worldwide. In adults, the virus causes severe acute respiratory distress syndrome (ARDS), while in children the disease seems to be milder, although a severe multisystem inflammatory syndrome (MIS-C) has been described. The aim was to describe and compare the characteristics of the severe COVID-19 disease in adults and children. METHODS: This prospective observational cohort study included the young adults and children infected with SARS-CoV-2 between March-June 2020 and admitted to the paediatric intensive care unit. The two populations were analysed and compared focusing on their clinical and analytical characteristics and outcomes. RESULTS: Twenty patients were included. There were 16 adults (80%) and 4 children (20%). No mortality was recorded. All the adults were admitted due to ARDS. The median age was 32 years (IQR 23.3-41.5) and the most relevant previous pathology was obesity (n = 7, 43.7%). Thirteen (81.3%) needed mechanical ventilation, with a median PEEP of 13 (IQR 10.5-14.5). Six (37.5%) needed inotropic support due to the sedation. Eight (50%) developed a healthcare-associated infection, the most frequent of which was central line-associated bloodstream infection (n = 7, 71.4%). One patient developed a partial pulmonary thromboembolism, despite him being treated with heparin. All the children were admitted due to MIS-C. Two (50%) required mechanical ventilation. All needed inotropic support, with a median vasoactive-inotropic score of 27.5 (IQR 17.5-30). The difference in the inotropic requirements between the two populations was statistically significant (37.5% vs. 100%, p < 0.001). The biomarker values were higher in children than in adults: mid-regional pro-adrenomedullin 1.72 vs. 0.78 nmol/L (p = 0.017), procalcitonin 5.7 vs. 0.19 ng/mL (p = 0.023), and C-reactive protein 328.2 vs. 146.9 mg/L (p = 0.005). N-terminal pro-B-type natriuretic peptide and troponins were higher in children than in adults (p = 0.034 and p = 0.039, respectively). CONCLUSIONS: Adults and children had different clinical manifestations. Adults developed severe ARDS requiring increased respiratory support, whereas children presented MIS-C with greater inotropic requirements. Biomarkers could be helpful in identifying susceptible patients, since they might change depending on the clinical features.

Pro-atrial natriuretic peptide and pro-adrenomedullin before cardiac surgery in children. Can we predict the future?

INTRODUCTION AND OBJECTIVE: Pro-atrial natriuretic peptide (proANP) and pro-adrenomedullin (proADM) levels increase in acute heart failure and sepsis. After cardiac surgery, children may require increased support in the intensive care unit and may develop complications. The aim of this study was to evaluate the utility of proANP and proADM values, determined prior to cardiac surgery, for predicting the need for increased respiratory or inotropic support during the post-operative period. METHODS: This was a prospective study in children. Biomarkers were analyzed before surgery using a single blood test. The primary endpoints were the need for greater respiratory and/or inotropic support during the post-operative period. Secondary endpoints were the relationship between these biomarkers and complications after surgery. RESULTS: One hundred thirteen patients were included. ProANP and proADM were higher in children who required greater respiratory and inotropic support, especially proANP; for increased respiratory support, 578.9 vs. 106.6 pmol/L (p = 0.004), and for increased inotropic support, 1938 vs. 110.4 pmol/L (p = 0.002). ProANP had a greater AUC than proADM for predicting increased respiratory support after surgery: 0.791 vs. 0.724. A possible cut-off point for proANP could be ≥ 325 pmol/L (sensitivity = 66.7% and specificity = 88.8%). In the multivariate analysis, the logarithmic transformation of proANP was independently associated with the need for increased respiratory support (OR = 3.575). Patients who presented a poor outcome after cardiac surgery also had higher biomarker values (proADM, p = 0.013; proANP, p = 0.001). CONCLUSIONS: Elevated proANP before cardiac surgery may identify which children will need more respiratory and inotropic support during the post-operative period.

End-of-life care in a pediatric intensive care unit: the impact of the development of a palliative care unit.

BACKGROUND: The purpose of this paper is to describe how end-of-life care is managed when life-support limitation is decided in a Pediatric Intensive Care Unit and to analyze the influence of the further development of the Palliative Care Unit. METHODS: A 15-year retrospective study of children who died after life-support limitation was initiated in a pediatric intensive care unit. Patients were divided into two groups, pre- and post-palliative care unit development. Epidemiological and clinical data, the decision-making process, and the approach were analyzed. Data was obtained from patient medical records. RESULTS: One hundred seventy-five patients were included. The main reason for admission was respiratory failure (86/175). A previous pathology was present in 152 patients (61/152 were neurological issues). The medical team and family participated together in the decision-making in 145 cases (82.8%). The family made the request in 10 cases (9 vs. 1, p = 0.019). Withdrawal was the main life-support limitation (113/175), followed by withholding life-sustaining treatments (37/175). Withdrawal was more frequent in the post-palliative group (57.4% vs. 74.3%, p = 0.031). In absolute numbers, respiratory support was the main type of support withdrawn. CONCLUSIONS: The main cause of life-support limitation was the unfavourable evolution of the underlying pathology. Families were involved in the decision-making process in a high percentage of the cases. The development of the Palliative Care Unit changed life-support limitation in our unit, with differences detected in the type of patient and in the strategy used. Increased confidence among intensivists when providing end-of-life care, and the availability of a Palliative Care Unit may contribute to improvements in the quality of end-of-life care.

Diagnostic and prognostic value of procalcitonin and mid-regional pro-adrenomedullin in septic paediatric patients.

Early diagnosis of sepsis and its severity stratification at admission is critical to improve patient outcomes and to ensure the optimal use of health care resources. In order to assess the diagnostic potential of mid-regional pro-adrenomedullin (MR-proADM) in septic paediatric patients in comparison with procalcitonin (PCT), and to evaluate the usefulness of a single early determination of MR-proADM as a stratification and severity prediction tool, a prospective observational study was conducted. Seventy-three paediatric patients with a suspicion of sepsis were included. A single blood test was carried out at initial time to analyse infection biomarkers. PCT values were significantly higher in septic patients in comparison with non-septic patients (p = 0.03) with an AUC of 0.748 (p = 0.003). Levels of MR-proADM significantly increased in patients with severe sepsis (p = 0.048), with an AUC of 0.729 (p = 0.013). MR-proADM showed a positive correlation with pSOFA, PRISM III, and PELOD-2 severity scores. Levels of MR-proADM were significantly higher in patients who required vasoactive drugs (p = 0.02) or presented renal dysfunction (p = 0.004).Conclusion: PCT appeared to be superior to MR-proADM in diagnosing sepsis. Determining MR-proADM plasma levels at the initial phase of sepsis could be a useful tool for sepsis stratification and morbidity prediction before organ failure occurs. The present results need to be assessed with larger sample size studies.What is Known:•CRP and PCT are already included in clinical practice to assess sepsis and estimate disease severity, although their sensitivity and specificity are lower than desired.•ADM is a protein that has immune and vascular modulation actions, and its blood levels are increased in adult and paediatric sepsis.•ADM is a promising tool for early diagnosis and prognostic assessment in adult sepsis.What is New:•PCT appeared to be superior to MR-proADM in diagnosing paediatric sepsis.•MR-proADM plasma levels could be a useful tool for paediatric sepsis stratification and morbidity prediction.

Risk stratification models for congenital heart surgery in children: Comparative single-center study.

OBJECTIVE: Three scores have been proposed to stratify the risk of mortality for each cardiac surgical procedure: The RACHS-1, the Aristotle Basic Complexity (ABC), and the STS-EACTS complexity scoring model. The aim was to compare the ability to predict mortality and morbidity of the three scores applied to a specific population. DESIGN: Retrospective, descriptive study. SETTING: Pediatric and neonatal intensive care units in a referral hospital. PATIENTS: Children under 18 years admitted to the intensive care unit after surgery. INTERVENTIONS: None. OUTCOME MEASURES: Demographic, clinical, and surgical data were assessed. Morbidity was considered as prolonged length of stay (LOS > 75 percentile), high respiratory (>72 hours of mechanical ventilation), and high hemodynamic support (inotropic support >20). RESULTS: One thousand and thirty-seven patients were included, in which 205 were newborns (18%). The category 2 was the most frequent in the three scores: In RACHS-1, ABC, 44.9%, and STS-EACTS, 40.8%. Newborns presented significant higher categories. Children required cardiopulmonary bypass in more occasions (P < .001) but the times of bypass and aortic cross-clamp were significantly higher in newborns (P < .001 and P = .016). Thirty-two patients died (2.8%). A quarter of patients had a prolonged LOS, 17%, a high respiratory support, and 7.1%, a high hemodynamic support. RACHS-1 (AUC 0.760) and STS-EACTS (AUC 0.763) were more powerful for predicting mortality and STS-EACTS for predicting prolonged LOS (AUC 0.733) and the need for high respiratory support (AUC 0.742). CONCLUSIONS: STS-EACTS seems to stratify better risk of mortality, prolonged LOS, and need for respiratory support after surgery.

Procalcitonin to stop antibiotics after cardiovascular surgery in a pediatric intensive care unit-The PROSACAB study.

INTRODUCTION AND OBJECTIVE: Children admitted to the pediatric intensive care unit after cardiovascular surgery usually require treatment with antibiotics due to suspicion of infection. The aim of this study was to assess the effectiveness of procalcitonin in decreasing the duration of antibiotic treatment in children after cardiovascular surgery. METHODS: Prospective, interventional study carried out in a pediatric intensive care unit. Included patients under 18 years old admitted after cardiopulmonary bypass. Two groups were compared, depending on the implementation of the PCT-guided protocol to stop or de-escalate the antibiotic treatment (Group 1, 2011-2013 and group 2, 2014-2018). This new protocol was based on the decrease of the PCT value by 20% or 50% with respect to the maximum value of PCT. Primary endpoints were mortality, stewardship indication, duration of antibiotic treatment, and antibiotic-free days. RESULTS: 886 patients were recruited. There were 226 suspicions of infection (25.5%), and they were confirmed in 38 cases (16.8%). The global rate of infections was 4.3%. 102 patients received broad-spectrum antibiotic (4.7±1.7 days in group 1, 3.9±1 days in group 2 with p = 0.160). The rate of de-escalation was higher in group 2 (30/62, 48.4%) than in group 1 (24/92, 26.1%) with p = 0.004. A reduction of 1.1 days of antibiotic treatment (group 1, 7.7±2.2 and group 2, 6.7±2.2, with p = 0.005) and 2 more antibiotic free-days free in PICU in group 2 were observed (p = 0.001), without adverse outcomes. CONCLUSIONS: Procalcitonin-guided protocol for stewardship after cardiac surgery seems to be safe and useful to decrease the antibiotic exposure. This protocol could help to reduce the duration of broad-spectrum antibiotics and the duration of antibiotics in total, without developing complications or adverse effects.

Prognostic value of biomarkers after cardiopulmonary bypass in pediatrics: The prospective PANCAP study.

OBJECTIVE: To assess the usefulness of procalcitonin, pro-adrenomedullin and pro-atrial natriuretic peptide as predictors of need for mechanical ventilation and postoperative complications (need for inotropic support and bacterial infection) in critically ill pediatric patients after cardiopulmonary bypass. DESIGN: A prospective, observational study. SETTING: Pediatric intensive care unit. PATIENTS: Patients under 18 years old admitted after cardiopulmonary bypass. MEASURAMENTS AND MAIN RESULTS: Serum levels of procalcitonin, pro-adrenomedullin and pro-atrial natriuretic peptide were determined immediately after bypass and at 24-36 hours. Their values were correlated with the need for mechanical ventilation, inotropic support and bacterial infection. One hundred eleven patients were recruited. Septal defects (30.6%) and cardiac valve disease (17.1%) were the most frequent pathologies. 40.7% required mechanical ventilation, 94.6% inotropic support and 15.3% presented invasive bacterial infections. Pro-adrenomedullin and pro-atrial natriuretic peptide showed significant high values in patients needing mechanical ventilation. Cut-off values higher than 1.22 nmol/L and 215.3 pmol/L, respectively for each biomarker, may indicate need for mechanical ventilation with an AUC of 0.721 and 0.746 at admission and 0.738 and 0.753 at 24-36 hours, respectively but without statistical differences. Pro-adrenomedullin and procalcitonin showed statistically significant high values in patients with bacterial infections. CONCLUSIONS: After bypass, pro-adrenomedullin and pro-atrial natriuretic peptide are suitable biomarkers to predict the need for mechanical ventilation. Physicians should be alert if the values of these markers are high so as not to progress to early extubation. Procalcitonin is useful for predicting bacterial infection. This is a preliminary study and more clinical studies should be done to confirm the value of pro-adrenomedullin and pro-atrial natriuretic peptide as biomarkers after cardiopulmonary bypass.