Background: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. 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 between March 2016 and January 2017. 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: Infants (n¼5609) 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 (SpO 2 <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]¼1.16; 95% confidence interval [CI], 1.04e1.28

Background: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. Methods: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. Results: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1e6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO 2 <90% for 60 s) was reported in 40%. No associated risk factors could be identified among comorbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. Conclusions:The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event. Clinical trial registration: NCT02350348.

and correlated well (r ϭ 0.85, P ϭ 0.02, n ϭ 7) with oxygen consumption calculated from blood flow, hemoglobin, and blood gas measurements (mean 22.8 Ϯ 4.7 mol⅐min Ϫ1 ⅐g dry wt Ϫ1). Local blood flow and oxygen consumption were significantly correlated (r ϭ 0.63 for pooled normalized data, P Ͻ 0.0001, n ϭ 60). We calculate that, in the heart at normal workload, the variance of left ventricular oxygen delivery at submilliliter resolution is explained for 43% by heterogeneity in oxygen demand. regional blood flow; metabolism; myocardium; magnetic resonance spectroscopy MYOCARDIAL BLOOD FLOW is highly heterogeneous, as demonstrated in many different species, with various methods (radioactive, colored and fluorescent microspheres, molecular tracers, MRI, and PET), and under different experimental circumstances, such as open-versus closed-chest and anesthetized versus awake animals (5,9,19,22,26,27). Myocardial perfusion shows similar heterogeneity in the human heart (47). This heterogeneity is largely of spatial nature, although there is also some temporal variation (27). Local blood flow can differ by a factor five among small areas of the left ventricle, even in the normal heart. Interestingly, regional blood flow is rather stable over a substantial time period, at least for several hours, but some data even indicate a relatively stable local blood flow over days (44). From an anatomic and mechanical point of view, this heterogeneity is difficult to understand because the heart appears rather homogeneous and biomechanical models predict homogeneous contraction. The question thus remains: which factors contribute to heterogeneous blood flow? Heterogeneity in oxygen consumption (V O 2 ) between different areas of the left ventricle may explain at least part of the heterogeneity of myocardial blood flow. Indeed, it has been shown in previous studies (9,19) that indirect indicators of local aerobic metabolism show heterogeneity. For instance, a correlation between local blood flow and fatty acid uptake has been shown (24). Others (38, 39) have reported a rather good correlation between local myocardial blood flow and local myocardial V O 2 (MV O 2 ) measured by [18 O]water in the isolated buffer-perfused rabbit heart. Low-flow areas had lower V O 2 and highflow areas had higher V O 2 . Further studies showed that areas of the left ventricle that receive a relatively low amount of blood flow are not in a hypoxic state, suggesting local adaptation of blood flow to oxygen demand (8,11,14). However, direct measurement of aerobic metabolic flux in small myocardial regions became possible only recently. Regional V O 2 and regional blood flow can be estimated with PET, although this technique still does not permit analysis at sufficiently high spatial resolution to study cardiac heterogeneity in small tissue areas (1,34,37).To investigate the distribution of MV O 2 at high spatial resolution, a new combination of isotope labeling protocol and mathematical analysis of 13 C incorporation into the tricarboxylic acid (TCA) cycle ...

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Measurement of local myocardial O(2) consumption (VO(2)) has been problematic but is needed to investigate the heterogeneity of aerobic metabolism. The goal of the present investigation was to develop a method to measure local VO(2) using small frozen myocardial samples, suitable for determining VO(2) profiles. In 26 isolated rabbit hearts, 1.5 mmol/l [2-(13)C]acetate was infused for 4 min, followed by 1.5 min of [1,2-(13)C]acetate. The left ventricular (LV) free wall was then quickly frozen. High-resolution (13)C-NMR spectra were measured from extracts taken from 2- to 3-mm thick transmural layer samples. The multiplet intensities of glutamate were analyzed with a computer model allowing simultaneous estimation of the absolute flux through the tricarboxylic acid cycle and the fractional contribution of acetate to acetyl CoA formation from which local VO(2) was calculated. The (13)C-derived VO(2) in the LV free wall was linearly related to "gold standard" VO(2) from coronary venous O(2) electrode measurements in the same region (r = 0.932, n = 22, P < 0.0001, slope 1.05) for control and lowered metabolic rates. The ratio of subendocardial to subepicardial VO(2) was 1.52 +/- 0.19 (SE, significantly >1, P < 0.025). Local myocardial VO(2) can now be quantitated with this new (13)C method to determine profiles of aerobic energy metabolism.