Prone positioning for non-intubated spontaneously breathing patients with acute hypoxaemic respiratory failure: a systematic review and meta-analysis.

BACKGROUND: Prone positioning in non-intubated spontaneously breathing patients is becoming widely applied in practice alongside noninvasive respiratory support. This systematic review and meta-analysis evaluates the effect, timing, and populations that might benefit from awake proning regarding oxygenation, mortality, and tracheal intubation compared with supine position in hypoxaemic acute respiratory failure. METHODS: We conducted a systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, CINAHL, and BMJ Best Practice until August 2021 (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD42021250322). Studies included comprise least-wise 20 adult patients with hypoxaemic respiratory failure secondary to acute respiratory distress syndrome or coronavirus disease (COVID-19). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and study quality was assessed using the Newcastle-Ottawa Scale and the Cochrane risk-of-bias tool. RESULTS: Fourteen studies fulfilled the selection criteria and 2352 patients were included; of those patients, 99% (n=2332/2352) had COVID-19. Amongst 1041 (44%) patients who were placed in the prone position, 1021 were SARS-CoV-2 positive. The meta-analysis revealed significant improvement in the PaO2/FiO2 ratio (mean difference -23.10; 95% confidence interval [CI]: -34.80 to 11.39; P=0.0001; I2=26%) after prone positioning. In patients with COVID-19, lower mortality was found in the group placed in the prone position (150/771 prone vs 391/1457 supine; odds ratio [OR] 0.51; 95% CI: 0.32-0.80; P=0.003; I2=48%), but the tracheal intubation rate was unchanged (284/824 prone vs 616/1271 supine; OR 0.72; 95% CI: 0.43-1.22; P=0.220; I2=75%). Overall proning was tolerated for a median of 4 h (inter-quartile range: 2-16). CONCLUSIONS: Prone positioning can improve oxygenation amongst non-intubated patients with acute hypoxaemic respiratory failure when applied for at least 4 h over repeated daily episodes. Awake proning appears safe, but the effect on tracheal intubation rate and survival remains uncertain.

Shifts in broadband power and alpha peak frequency observed during long-term isolation.

Prolonged periods of social isolation and spatial confinement do not only represent an issue that needs to be faced by a few astronauts during space missions, but can affect all of us as recently shown during pandemic situations. The fundamental question, how the brain adapts to periods of sensory deprivation and re-adapts to normality, has only received little attention. Here, we use eyes closed and eyes open resting-state electroencephalographic (EEG) recordings to investigate how neural activity is altered during 120 days of isolation in a spatially confined, space-analogue environment. After disentangling oscillatory patterns from 1/f activity, we show that isolation leads to a reduction in broadband power and a flattening of the 1/f spectral slope. Beyond that, we observed a reduction in alpha peak frequency during isolation, but did not find strong evidence for isolation-induced changes that are of oscillatory nature. Critically, all effects reversed upon release from isolation. These findings suggest that isolation and concomitant sensory deprivation lead to an enhanced cortical deactivation which might be explained by a reduction in the mean neuronal population firing rate.

Delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the olfactory bulb in freely behaving rats.

Respiratory rhythm (RR) during sniffing is known to couple with hippocampal theta rhythm. However, outside of the short sniffing bouts, a more stable ~ 2 Hz RR was recently shown to rhythmically modulate non-olfactory cognitive processes, as well. The underlying RR coupling with wide-spread forebrain activity was confirmed using advanced techniques, creating solid premise for investigating how higher networks use this mechanism in their communication. Here we show essential differences in the way prefrontal cortex (PFC) and hippocampus (HC) process the RR signal from the olfactory bulb (OB) that may support dynamic, flexible PFC-HC coupling utilizing this input. We used inter-regional coherences and their correlations in rats, breathing at low rate (~ 2 Hz), outside of the short sniffing bouts. We found strong and stable OB-PFC coherence in wake states, contrasting OB-HC coherence which was low but highly variable. Importantly, this variability was essential for establishing PFC-HC synchrony at RR, whereas variations of RRO in OB and PFC had no significant effect. The findings help to understand the mechanism of rhythmic modulation of non-olfactory cognitive processes by the on-going regular respiration, reported in rodents as well as humans. These mechanisms may be impaired when nasal breathing is limited or in OB-pathology, including malfunctions of the olfactory epithelium due to infections, such as in Covid-19.

Early, awake proning in emergency department patients with COVID-19.

OBJECTIVE: Proning has been shown to improve oxygenation and mortality in certain populations of intubated patients with acute respiratory distress syndrome. Small observational analyses of COVID-19 patients suggest awake proning may lead to clinical improvement. Data on safety and efficacy is lacking. We sought to describe the effect of proning on oxygenation in nonintubated COVID-19 patients. We also evaluated feasibility, safety, and other physiological and clinical outcomes associated with this intervention. METHODS: We conducted a prospective, observational cohort study of nonintubated patients with COVID-19 who underwent proning per an Emergency Department (ED) clinical protocol. Patients with mild to moderate respiratory distress were included. We calculated change in oxygenation by comparing the oxygen saturation to fraction of inspired oxygen ratio (SpO2:FiO2) during the five minutes prior to proning and first 30 min of proning. We also captured data on respiratory rate, duration of proning, need for intubation, intensive care unit admission, survival to discharge. RESULTS: Fifty-two patients were enrolled. Thirty were excluded for not meeting protocol inclusion criteria or missing baseline oxygenation data, leaving 22 for analysis. The SpO2:FiO2 ratio increased by a median of 5 (IQR: 0-15) in the post-proning period compared to the pre-proning period (median: 298 (IQR: 263-352) vs 295 (IQR: 276-350), p = 0.01). Respiratory rate did not change significantly between time periods. No immediate adverse events occurred during proning. Five patients (23%) were intubated within 48 h of admission. CONCLUSION: Early, awake proning may be feasible in select COVID-19 patients and was associated with improved oxygenation.