The propofol infusion syndrome: more puzzling evidence on a complex and poorly characterized disorder

The propofol infusion syndrome is a potentially devastating cardiovascular and metabolic derangement that has been described in both pediatric and adult patients sedated with propofol. Despite a large number of case reports that have appeared in the literature since 1992, the precise clinical features and pathophysiology of this disorder remain uncertain. Historically, the syndrome has been characterized by the occurrence of lactic acidosis, rhabdomyolysis, and circulatory collapse after several days of high-dose propofol infusion. The affected patients were typically young and critically ill, and the reported mortality was high. More recently, a number of atypical cases have been reported with favorable outcomes. These occurred after short-term or lower-dose infusions in noncritically ill patients in whom generally only a subset of the classical syndrome features was observed. It remains unclear whether these reports reflect true propofol infusion syndrome detected at an earlier and more salvageable stage, or mere associations with the use of sedative agents in general. Without better information on the true incidence of the propofol infusion syndrome, clinical guidelines on the safe use of this drug remain unsupported by good evidence

Two-step interpretable modeling of ICU-AIs

We present a novel methodology for integrating high resolution longitudinal data with the dynamic prediction capabilities of survival models. The aim is two-fold: to improve the predictive power while maintaining the inter- pretability of the models. To go beyond the black box paradigm of artificial neural networks, we propose a parsimonious and robust semi-parametric approach (i.e., a landmarking competing risks model) that combines routinely collected low-resolution data with predictive features extracted from a convolutional neural network, that was trained on high resolution time-dependent information. We then use saliency maps to analyze and explain the extra predictive power of this model. To illustrate our methodology, we focus on healthcare-associated infections in patients admitted to an intensive care unit

Interrater agreement in classifying infections during extracorporeal membrane oxygenation

Infectious complications are common during extracorporeal membrane oxygenation (ECMO) and may negatively impact outcomes. However, there is considerable variation in the reported rates of incidence, which hampers the use of infections as a quality benchmark for ECMO centers. To assess the contributing role of poor interrater agreement, three independent raters reviewed medical records from all intensive care unit (ICU) patients who received ECMO for &gt;24 h in our tertiary center between October 2019 and October 2021 for suspected episodes of infection, which were rated based on their date of onset and presumed site/diagnosis. To establish a gold standard, any discrepancies were resolved using an expert panel consisting of two intensivists/infectious disease specialists. During 83 ECMO-runs in 77 patients, we observed a total of 62 adjudicated infectious episodes (incidence rate 62, 95% CI: 48–80, per 1000 days at risk). Among 81 episodes suspected by at least one observer, 66 (81%) were identified by two, and only 44 (54%) by all three raters, resulting in Fleiss’ kappa of 0.10 (95% CI: 0.00–0.19; slight agreement). However, if raters concurred regarding infection onset, subsequent agreement on infection site was good (concordance 89%; kappa 0.85, 95% CI: 0.72–0.98; near perfect agreement). In conclusion, adjudication of infectious episodes during ECMO is associated with poor interrater agreement regarding occurrence—but not site—of infection. This finding might partially explain the significant disparities observed in reported infection rates during ECMO, emphasizing the need for caution when interpreting infection data in this particular population due to the potential for inherent measurement error.</p

Nebulised amphotericin B to eradicate Candida colonisation from the respiratory tract in critically ill patients receiving selective digestive decontamination: a cohort study

INTRODUCTION: Colonisation of the lower respiratory tract with Candida species occurs in 25% of mechanically ventilated critically ill patients, and is associated with increased morbidity. Nebulised amphotericin B has been used to eradicate Candida as part of selective decontamination of the digestive tract (SDD) protocols, but its effectiveness is unknown. We aimed to determine the effectiveness of nebulised amphotericin B in eradicating Candida respiratory tract colonisation in patients receiving SDD. METHODS: We included consecutive mechanically ventilated patients during a four-year period. Microbiological screening was performed upon admission and twice weekly thereafter according to a standardised protocol. A colonisation episode was defined as the presence of Candida species in two consecutive sputum samples taken at least one day apart. To correct for time-varying bias and possible confounding, we used a multistate approach and performed time-varying Cox regression with adjustment for age, disease severity, Candida load at baseline and concurrent corticosteroid use. RESULTS: Among 1,819 patients, colonisation with Candida occurred 401 times in 363 patients; 333 of these events were included for analysis. Decolonisation occurred in 51 of 59 episodes (86%) and in 170 of 274 episodes (62%) in patients receiving and not receiving nebulised amphotericin B, respectively. Nebulised amphotericin B was associated with an increased rate of Candida eradication (crude HR 2.0; 95% CI 1.4 to 2.7, adjusted HR 2.2; 95% CI 1.6 to 3.0). Median times to decolonisation were six and nine days, respectively. The incidence rate of ventilator-associated pneumonia, length of stay and mortality did not differ between both groups. CONCLUSIONS: Nebulised amphotericin B reduces the duration of Candida colonisation in the lower respiratory tracts of mechanically ventilated critically ill patients receiving SDD, but data remain lacking that this is associated with a meaningful improvement in clinical outcomes. Until more evidence becomes available, nebulised amphotericin B should not be used routinely as part of the SDD protocol

Identification of a novel protein containing two C2 domains selectively expressed in the rat brain and kidney

AbstractWe have isolated and characterized a rat brain cDNA clone which encodes a new protein of 474 amino acids in length which contains two C2 domains structurally homologous to those present in synaptotagmins. The overall amino acid identity in C2 domains between this protein and the synaptotagmins is 36–44%. This protein also contains 3 putative consensus sequences for phosphorylation by cAMP-dependent protein kinase. RNA blot hybridization revealed a 3.0 kb transcript abundantly expressed only in the rat brain and the kidney. Thus, we called this brain/kidney protein (B/K). In situ hybridization and Northern blot analyses showed that the B/K transcript was found in forebrain including the olfactory bulb, cerebral cortex, hippocampus, and hypothalamus. In the kidney, high levels of B/K transcript were expressed in the papillary region of the inner medulla, the inner stripe of the outer medulla and the cortex. The selective expression in forebrain and kidney suggests that B/K may be involved in similar cAMP-dependent processes at these very different sites

Схема когенерации с размещением противодавленческой и гидропаровой турбин на общем валу с газопоршневой установкой

Показана перспективність використання когенераційних технологій для підвищення рентабельності вугільних підприємств. Розглянуто схему з розміщенням турбіни з противотиском і гідропарової турбіни на одному валу з газопоршневою установкою. Використання даної схеми для утилізації надлишкового тепла шахтних енергокомплексів дозволить отримати коефіцієнт корисної дії 64 % та зменшити витрати палива.In this paper the perspective use of cogeneration technology enhance the profitability of coal enterprises was discussed. The scheme with setting back-pressures and steam-water turbines on one shaft of gas engine was considered. Using this scheme for utilization of surplus heat mine energy complexes will provide efficiency of 64% and reduce fuel

Interrater agreement in classifying infections during extracorporeal membrane oxygenation

Infectious complications are common during extracorporeal membrane oxygenation (ECMO) and may negatively impact outcomes. However, there is considerable variation in the reported rates of incidence, which hampers the use of infections as a quality benchmark for ECMO centers. To assess the contributing role of poor interrater agreement, three independent raters reviewed medical records from all intensive care unit (ICU) patients who received ECMO for >24 h in our tertiary center between October 2019 and October 2021 for suspected episodes of infection, which were rated based on their date of onset and presumed site/diagnosis. To establish a gold standard, any discrepancies were resolved using an expert panel consisting of two intensivists/infectious disease specialists. During 83 ECMO-runs in 77 patients, we observed a total of 62 adjudicated infectious episodes (incidence rate 62, 95% CI: 48–80, per 1000 days at risk). Among 81 episodes suspected by at least one observer, 66 (81%) were identified by two, and only 44 (54%) by all three raters, resulting in Fleiss’ kappa of 0.10 (95% CI: 0.00–0.19; slight agreement). However, if raters concurred regarding infection onset, subsequent agreement on infection site was good (concordance 89%; kappa 0.85, 95% CI: 0.72–0.98; near perfect agreement). In conclusion, adjudication of infectious episodes during ECMO is associated with poor interrater agreement regarding occurrence—but not site—of infection. This finding might partially explain the significant disparities observed in reported infection rates during ECMO, emphasizing the need for caution when interpreting infection data in this particular population due to the potential for inherent measurement error

Clinical decision support for ExtraCorporeal Membrane Oxygenation:Will we fly by wire?

Prognostic modelling techniques have rapidly evolved over the past decade and may greatly benefit patients supported with ExtraCorporeal Membrane Oxygenation (ECMO). Epidemiological and computational physiological approaches aim to provide more accurate predictive assessments of ECMO-related risks and benefits. Implementation of these approaches may produce predictive tools that can improve complex clinical decisions surrounding ECMO allocation and management. This Review describes current applications of prognostic models and elaborates on upcoming directions for their clinical applicability in decision support tools directed at improved allocation and management of ECMO patients. The discussion of these new developments in the field will culminate in a futuristic perspective leaving ourselves and the readers wondering whether we may “fly ECMO by wire” someday.</p