Oxygenation during the apnoeic phase preceding intubation in adults in prehospital, emergency department, intensive care and operating theatre environments.

BACKGROUND: Apnoeic oxygenation is the delivery of oxygen during the apnoeic phase preceding intubation. It is used to prevent respiratory complications of endotracheal intubation that have the potential to lead to significant adverse events including dysrhythmia, haemodynamic decompensation, hypoxic brain injury and death. Oxygen delivered by nasal cannulae during the apnoeic phase of intubation (apnoeic oxygenation) may serve as a non-invasive adjunct to endotracheal intubation to decrease the incidence of hypoxaemia, morbidity and mortality. OBJECTIVES: To evaluate the benefits and harms of apnoeic oxygenation before intubation in adults in the prehospital, emergency department, intensive care unit and operating theatre environments compared to no apnoeic oxygenation during intubation. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 4 November 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs that compared the use of any form of apnoeic oxygenation including high flow and low flow nasal cannulae versus no apnoeic oxygenation during intubation. We defined quasi-randomization as participant allocation to each arm by means that were not truly random, such as alternation, case record number or date of birth. We excluded comparative prospective cohort and comparative retrospective cohort studies, physiological modelling studies and case reports. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. hospital stay and 2. incidence of severe hypoxaemia. Our secondary outcomes were 3. incidence of hypoxaemia, 4. lowest recorded saturation of pulse oximetry (SpO2), 5. intensive care unit (ICU) stay, 6. first pass success rate, 7. adverse events and 8. MORTALITY: We used GRADE to assess certainty of evidence. MAIN RESULTS: We included 23 RCTs (2264 participants) in our analyses. Eight studies (729 participants) investigated the use of low-flow (15 L/minute or less), and 15 studies (1535 participants) investigated the use of high-flow (greater than 15 L/minute) oxygen. Settings were varied and included the emergency department (2 studies, 327 participants), ICU (7 studies, 913 participants) and operating theatre (14 studies, 1024 participants). We considered two studies to be at low risk of bias across all domains. None of the studies reported on hospital length of stay. In predominately critically ill people, there may be little to no difference in the incidence of severe hypoxaemia (SpO2 less than 80%) when using apnoeic oxygenation at any flow rate from the start of apnoea until successful intubation (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.66 to 1.11; P = 0.25, I² = 0%; 15 studies, 1802 participants; low-certainty evidence). There was insufficient evidence of any effect on the incidence of hypoxaemia (SpO2 less than 93%) (RR 0.58, 95% CI 0.23 to 1.46; P = 0.25, I² = 36%; 3 studies, 489 participants; low-certainty evidence). There may be an improvement in the lowest recorded oxygen saturation, with a mean increase of 1.9% (95% CI 0.75% to 3.05%; P < 0.001, I² = 86%; 15 studies, 1525 participants; low-certainty evidence). There may be a reduction in the duration of ICU stay with the use of apnoeic oxygenation during intubation (mean difference (MD) ‒1.13 days, 95% CI ‒1.51 to ‒0.74; P < 0.0001, I² = 46%; 5 studies, 815 participants; low-certainty evidence). There may be little to no difference in first pass success rate (RR 1.00, 95% CI 0.93 to 1.08; P = 0.79, I² = 0%; 8 studies, 826 participants; moderate-certainty evidence). There may be little to no difference in incidence of adverse events including oral trauma, arrhythmia, aspiration, hypotension, pneumonia and cardiac arrest when apnoeic oxygenation is used. There was insufficient evidence about any effect on mortality (RR 0.84, 95% CI 0.70 to 1.00; P = 0.06, I² = 0%; 6 studies, 1015 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There was some evidence that oxygenation during the apnoeic phase of intubation may improve the lowest recorded oxygen saturation. However, the differences in oxygen saturation were unlikely to be clinically significant. This did not translate into any measurable effect on the incidence of hypoxaemia or severe hypoxaemia in a group of predominately critically ill people. We were unable to assess the influence on hospital length of stay; however, there was a reduction in ICU stay in the apnoeic oxygenation group. The mechanism for this is unclear as there was little to no difference in first pass success or adverse event rates.

1H NMR-based metabolite profiling for biomarker identification.

The metabolome is affected by individual physiologic and pathophysiologic states as well as the environment. Metabolomics has become crucial approach for clinical studies, providing a better understanding of disease mechanisms. The expansion of analytical methods aiming at performing detailed analysis of biofluids has led to the characterization of many disease biomarkers. NMR provides faster and more comprehensive assessment of the biological samples in human models. NMR-based profiling studies aimed at identifying biomarkers for specific diseases has significantly increased over the last few years. These have attempted to correlate human pathophysiology with alterations in the metabolic profile of common biofluids such as urine, plasma and serum. In this context, NMR-based untargeted metabolomics has become an important adjunct for the identification of biomarkers in disease research, not only for early diagnosis purposes, but also for therapy prediction, precise prognosis or monitoring of disease progression. This review critically discusses recent findings of urine (non-invasive) and blood serum and plasma (minimally invasive) metabolomics, focusing on key role of metabolites and their use as potential biomarkers for diagnostic purposes.

Cebranopadol: novel dual opioid/NOP receptor agonist analgesic.

WHAT IS KNOWN AND OBJECTIVE: Chronic pain presents a difficult clinical challenge because of the limited efficacy, the limiting adverse-effect profile or the abuse potential of current analgesic options. Cebranopadol is a novel new agent in clinical trials that combines dual agonist action at opioid and nociceptin/orphanin FQ peptide (NOP) receptors. It is the first truly unique, centrally acting analgesic in several years. We here review the basic and clinical pharmacology of cebranopadol. METHODS: Published literature and Internet sources were searched to identify information related to the basic science (pharmacology and medicinal chemistry) and development (clinical trial) information on the mechanism of dual opioid and NOP receptor pharmacologic action in general, and for cebranopadol in particular. The identified sources were reviewed and the information synthesized. RESULTS: The preclinical testing of cebranopadol has characterized it as a dual opioid and NOP receptor agonist that displays antinociceptive and antihyperalgesic action in a variety of acute and chronic pain models in animals. Unlike most current traditional opioids, it is generally more potent against neuropathic than nociceptive pain. Several phase 2 clinical trials have been completed. WHAT IS NEW AND CONCLUSION: Despite the medical need, a truly novel centrally acting analgesic has not been developed in many years. Cebranopadol represents a truly novel mechanistic approach. Its actual place in pain pharmacotherapy awaits the results of phase 3 clinical trials.

Asma y toxocarosis encubierta / Asthma and covert toxocariasis

Se estudió la relación entre asma bronquial y toxocarosis encubierta. Se seleccionaron 38 pacientes con síndrome de asma bronquial. Se estabelecieron criterios de inclusión/exclusión. Como población control se evaluaron 44 pacientes sin asma con los mismos criterios. Los anticuerpos antitoxocara de tipo IgG e IgE se detectaron mediante enzimoinmunoanálisis (ELISA). Las pruebas cutáneas se realizaron mediante inyección de alergenos habituales y de material excretor/secretor de Toxocara canis obtenido por cultivo in vitro de larvas en estadio II (Ag E/S). Dentro de la población con asma resultó serológicamente positiva el 68.42 por ciento, diferenciándose significativamente de la población control (13.63 por ciento). El porcentaje de pacientes asmáticos con ambos marcadores antitoxocara positivos fue 26.31 por ciento. En la población control fue 4.54 por ciento. El 100 por ciento de los pacientes con asma y seropositividad para IgE antitoxocara dieron reactividad cutánea para el Ag E/S de T. canis. Se concluye que el grupo de pacientes con asma bronquial presentó una indudable asociación con los marcadores serológicos antitoxocara IgE e IgG positivos y con la reactvidad cutánea al Ag E/S, por lo que podría inferirse que cursan una toxocarosis encubierta.

Asma y toxocarosis encubierta / Asthma and covert toxocariasis

Se estudió la relación entre asma bronquial y toxocarosis encubierta. Se seleccionaron 38 pacientes con síndrome de asma bronquial. Se estabelecieron criterios de inclusión/exclusión. Como población control se evaluaron 44 pacientes sin asma con los mismos criterios. Los anticuerpos antitoxocara de tipo IgG e IgE se detectaron mediante enzimoinmunoanálisis (ELISA). Las pruebas cutáneas se realizaron mediante inyección de alergenos habituales y de material excretor/secretor de Toxocara canis obtenido por cultivo in vitro de larvas en estadio II (Ag E/S). Dentro de la población con asma resultó serológicamente positiva el 68.42 por ciento, diferenciándose significativamente de la población control (13.63 por ciento). El porcentaje de pacientes asmáticos con ambos marcadores antitoxocara positivos fue 26.31 por ciento. En la población control fue 4.54 por ciento. El 100 por ciento de los pacientes con asma y seropositividad para IgE antitoxocara dieron reactividad cutánea para el Ag E/S de T. canis. Se concluye que el grupo de pacientes con asma bronquial presentó una indudable asociación con los marcadores serológicos antitoxocara IgE e IgG positivos y con la reactvidad cutánea al Ag E/S, por lo que podría inferirse que cursan una toxocarosis encubierta. (AU)