Resting Energy Expenditure assessment in mechanically ventilated critically ill children: the importance of Indirect Calorimetry

Introduction. Malnutrition is common in critically ill children, and is considered a negative prognostic factor for their clinical outcomes1,2. Traditionally, Resting Energy Expenditure (REE) is calculated using predictive equations. These equations might be inaccurate in the critical scenario. Indirect Calorimetry (IC) is the gold standard to measure REE and allows tailored nutrition support3 . Aim of the study was to evaluate the accuracy of commonly employed equations as compared to IC-derived values in critically ill children. Methods. Children admitted to our unit between January 2017 and March 2019, aged <18 years and mechanically ventilated were enrolled. Endotracheal tube leak >10% and/or a fraction of inspired oxygen 650.6 constituted exclusion criteria. Harris-Benedict, Schofield and WHO formulae were applied to estimate REE. We performed IC for 30 minutes and REE was measured. The agreement between IC- and equation-based values of REE was assessed via paired t-test and BlandAltman analysis. Data are expressed as mean and standard deviation. Statistical significance was defined as p<0.05. Results. Forty-four critically ill children (4.3\ub14.2 years, 18.1\ub116.4 kg) admitted for acute respiratory failure (n=24), neurological (n=13) or other diseases (n=7) were studied. Measured REE ranged between 16 and 89 kcal/kg/die (mean 43\ub115). Typically, all formulae significantly over-estimated the REE, as compared to IC (Table 1). Furthermore, the Bland-Altman analysis revealed wide limits of agreement, suggesting low accuracy of the prediction equations. Conclusions. In critically ill, mechanically ventilated patients REE is on average significantly lower than predicted by currently applied equations. This finding might be explained by a reduced work of breathing and/or the use of sedatives and paralyzing agents. Measurement of REE through IC is essential to avoid over/underfeeding in this population. References 1. Agostoni C et al. JPGN 2016 2. Taku Oshima et al. Clinical Nutr 2017 3. Smallwood CD et al. J Pediatr. 201

Gas-exchange and resting energy expenditure measurement with indirect calorimetry in children supported with non-invasive ventilation

Introduction. Nutrition plays a fundamental role in critically ill children and personalized nutritional therapy requires the measurement of resting energy expenditure (REE) [1-2]. Indirect calorimetry (IC) is the gold standard for REE assessment and is based on V\ue22fO2 and V\ue22fCO2 measurements. Furthermore, IC provides information on carbohydrates/lipids consumption by defining the respiratory quotient (RQ). However, while IC is validated for spontaneously breathing and mechanically ventilated patients, it is not for patients undergoing non-invasive ventilation (NIV) [3]. Aim of the study is therefore to validate IC for children undergoing NIV by comparing IC results obtained during spontaneous breathing with data gathered during NIV-CPAP (continuous positive airway pressure). Methods. Patients (age <6 years) admitted to our pediatric intensive care unit (PICU) and weaning from NIV-CPAP were enrolled. Two IC measurements (Canopy mode) were performed for 20 minutes in randomized order in the following conditions: 1) Spontaneous breathing (SB), 2) NIV-CPAP (performed by single-limb circuit and vented mask). Average values for V\ue22fCO2 , V\ue22fO2, RQ and REE were obtained in the two conditions. Comparison between groups was performed via paired t-test. Agreement was assessed via Bland-Altman analysis. Statistical significance was defined as p<0.05. Results. Four patients (median age 8 months, median weight 8 kg) were enrolled. V\ue22fCO2 , V\ue22fO2, RQ and REE did not differ significantly between groups. Limits of agreement (LOA) and BIAS indicate a good agreement between the two measures (Table 1). Conclusions. Our preliminary data suggest that IC can be accurately performed in children undergoing NIV using a single limb circuit with intentional leaks. These results need to be confirmed on a broader cohort of critically ill children. References 1. De Cosmi V et al. Nutrients. 2017, 18:9 2. Mehta NM et al. Pediatr Crit Care Med. 2017, 18:675-715 3. Taku Oshima et al. Clinical Nutr 2017; 36:651-66

Efficacy and safety of exogenous surfactant therapy in patients under 12 months of age invasively ventilated for severe bronchiolitis (SURFABRON): Protocol for a multicentre, randomised, double-blind, controlled, non-profit trial

Introduction Some evidence indicates that exogenous surfactant therapy may be effective in infants with acute viral bronchiolitis, even though more confirmatory data are needed. To date, no large multicentre trials have evaluated the effectiveness and safety of exogenous surfactant in severe cases of bronchiolitis requiring invasive mechanical ventilation (IMV). Methods and analysis This is a multicentre randomised, placebo-controlled, double-blind study, performed in 19 Italian paediatric intensive care units (PICUs). Eligible participants are infants under the age of 12 months hospitalised in a PICU, suffering from severe acute hypoxaemic bronchiolitis, requiring IMV. We adopted a more restrictive definition of bronchiolitis, including only infants below 12 months of age, to maintain the population as much homogeneous as possible. The primary outcome is to evaluate whether exogenous surfactant therapy (Curosurf, Chiesi Pharmaceuticals, Italy) is effective compared with placebo (air) in reducing the duration of IMV in the first 14 days of hospitalisation, in infants suffering from acute hypoxaemic viral bronchiolitis. Secondary outcomes are duration of non-invasive mechanical ventilation in the post-extubation phase, number of cases requiring new intubation after previous extubation within 14 days from randomisation, PICU and hospital length of stay (LOS), duration of oxygen dependency, effects on oxygenation and ventilatory parameters during invasive mechanical respiratory support, need for repeating treatment within 24 hours of first treatment, use of other interventions (eg, high-frequency oscillatory ventilation, nitric oxide, extracorporeal membrane oxygenation), mortality within the first 14 days of PICU stay and before hospital discharge, side effects and serious adverse events. Ethics and dissemination The trial design and protocol have received approval by the Italian National Agency for Drugs (AIFA) and by the Regional Ethical Committee of Verona University Hospital (1494CESC). Findings will be disseminated through publication in peer-reviewed journals, conference/meeting presentations and media. Trial registration number Clinicaltrials.gov, issue date 22 May 2019. NCT03959384

Corrigendum to ‘Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study’ (Br J Anaesth 2021; 126: 1173–81) (British Journal of Anaesthesia (2021) 126(6) (1173–1181), (S0007091221001161), (10.1016/j.bja.2021.02.021))

The authors regret that errors were present in the above article. On page 1174, in the second paragraph of the Statistical methods section, the second sentence should read as follows: The incidence of difficult intubation was determined including those whose tracheas were already intubated and is reported as a percentage with a 95% exact binomial CI. On page 1175, in the third paragraph of the Statistical methods section ‘mean standardised difference (MSD)’ should read ‘standardised mean difference (SMD)’ The authors would like to apologise for any inconvenience caused

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN A multicentre observational study. SETTING The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing perioperative red blood cell transfusions strategies