Oxygenation targets in ICU patients with COVID-19: A post hoc subgroup analysis of the HOT-ICU trial.

BACKGROUND: Supplemental oxygen is the key intervention for severe and critical COVID-19 patients. With the unstable supplies of oxygen in many countries, it is important to define the lowest safe dosage. METHODS: In spring 2020, 110 COVID-19 patients were enrolled as part of the Handling Oxygenation Targets in the ICU trial (HOT-ICU). Patients were allocated within 12 h of ICU admission. Oxygen therapy was titrated to a partial pressure of arterial oxygen (PaO2 ) of 8 kPa (lower oxygenation group) or a PaO2 of 12 kPa (higher oxygenation group) during ICU stay up to 90 days. We report key outcomes at 90 days for the subgroup of COVID-19 patients. RESULTS: At 90 days, 22 of 54 patients (40.7%) in the lower oxygenation group and 23 of 55 patients (41.8%) in the higher oxygenation group had died (adjusted risk ratio: 0.87; 95% confidence interval, 0.58-1.32). The percentage of days alive without life support was significantly higher in the lower oxygenation group (p = 0.03). The numbers of severe ischemic events were low with no difference between the two groups. Proning and inhaled vasodilators were used more frequently, and the positive end-expiratory pressure was higher in the higher oxygenation group. Tests for interactions with the results of the remaining HOT-ICU population were insignificant. CONCLUSIONS: Targeting a PaO2 of 8 kPa may be beneficial in ICU patients with COVID-19. These results come with uncertainty due to the low number of patients in this unplanned subgroup analysis, and insignificant tests for interaction with the main HOT-ICU trial. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT03174002. Date of registration: June 2, 2017.

A Tale of Two Waves: Changes in the Use of Noninvasive Ventilation and Prone Positioning in Critical Care Management of Coronavirus Disease 2019.

New treatments and increased experience are changing the management of hospitalized coronavirus disease 2019 patients but the impact on ICU management is unclear. OBJECTIVES: To examine characteristics, ventilatory management, and outcomes of critically ill patients in two distinct waves of the pandemic. DESIGN SETTING AND PARTICIPANTS: Observational cohort study in an ICU in a single-center university-affiliated U.K. hospital. Two-hundred ten adults with coronavirus disease 2019 admitted to ICU between March 17, 2020, to May 31, 2020, and September 1, 2020, to December 10, 2020, with hourly data and 100% follow-up to ICU discharge. MAIN OUTCOMES AND MEASURES: Data were extracted from the electronic medical record for patient characteristics and clinical data. Patients were classified into distinct waves of the pandemic and assessed for differences between the two waves. RESULTS: The duration of noninvasive ventilation/nasal high flow increased in wave 2 versus wave 1, both in self-ventilating patients (107 vs 72 hr; p = 0.02), and in those ultimately requiring invasive mechanical ventilation (34 vs 10 hr; p = 0.02). The proportion of survivors treated without invasive mechanical ventilation increased in wave 2 (59% vs 39%; p = 0.01). In both waves, longer duration of noninvasive ventilation/nasal high flow prior to intubation was associated with higher ICU mortality (survivors 10 hr [4-21 hr] vs nonsurvivors 50 hr [23-124 hr]; p < 0.01). Proned invasive mechanical ventilation was common (54.7%) and prolonged. In wave 2, invasive mechanical ventilation patients were generally more hypoxic with proning initiated at lower Pao2/Fio2 ratios (81 vs 116 mm Hg; p = 0.02) and yielding smaller improvements in Fio2 requirements. Continued proning episodes despite poor responses were commonplace and typically futile. Length of stay for patients requiring tracheostomy increased markedly in wave 2 (51.3 vs 33.7 d; p = 0.03). Overall survival remained similar in wave 2 (68.0% vs 60.9%; p = 0.31). CONCLUSIONS AND RELEVANCE: Our data suggest that management of critically ill coronavirus disease 2019 patients is changing with more survivors avoiding invasive mechanical ventilation. Duration of noninvasive ventilation/nasal high flow use is increasing, which may be associated with worsening outcomes for individuals who require invasive mechanical ventilation. Among invasively ventilated patients, changes in the use of and response to prone positioning and increased length of stay following tracheostomy may imply that the care of these patients is becoming more challenging.

The cerebral cost of breathing: an FMRI case-study in congenital central hypoventilation syndrome.

Certain motor activities--like walking or breathing--present the interesting property of proceeding either automatically or under voluntary control. In the case of breathing, brainstem structures located in the medulla are in charge of the automatic mode, whereas cortico-subcortical brain networks--including various frontal lobe areas--subtend the voluntary mode. We speculated that the involvement of cortical activity during voluntary breathing could impact both on the "resting state" pattern of cortical-subcortical connectivity, and on the recruitment of executive functions mediated by the frontal lobe. In order to test this prediction we explored a patient suffering from central congenital hypoventilation syndrome (CCHS), a very rare developmental condition secondary to brainstem dysfunction. Typically, CCHS patients demonstrate efficient cortically-controlled breathing while awake, but require mechanically-assisted ventilation during sleep to overcome the inability of brainstem structures to mediate automatic breathing. We used simultaneous EEG-fMRI recordings to compare patterns of brain activity between these two types of ventilation during wakefulness. As compared with spontaneous breathing (SB), mechanical ventilation (MV) restored the default mode network (DMN) associated with self-consciousness, mind-wandering, creativity and introspection in healthy subjects. SB on the other hand resulted in a specific increase of functional connectivity between brainstem and frontal lobe. Behaviorally, the patient was more efficient in cognitive tasks requiring executive control during MV than during SB, in agreement with her subjective reports in everyday life. Taken together our results provide insight into the cognitive and neural costs of spontaneous breathing in one CCHS patient, and suggest that MV during waking periods may free up frontal lobe resources, and make them available for cognitive recruitment. More generally, this study reveals how the active maintenance of cortical control over a continuous motor activity impacts on brain functioning and cognition.

alpha4beta2-nicotinic receptor binding with 5-IA in Alzheimer's disease: methods of scan analysis.

Five patients with Alzheimer's disease and five healthy volunteers were examined by SPECT with the nicotinic receptor ligand 123I-5-IA-85380. Patients were scanned before and after 6 weeks of treatment with donepezil. Quantification by regions of interest was reliable and the optimal normalisation procedure used cerebellar ratios. We found relative reductions in 5-IA binding capacity in patients in thalamus, frontal and central regions of interest of approximately one standard deviation unit (Cohen's d = 1). Reductions in binding after treatment with the acetylcholinesterase inhibitor donepezil of the same magnitude occurred in the brain stem. The study was clearly too small to confirm group differences, but it suggests that 5-IA can be used to examine both group differences and treatment effects in patients with Alzheimer's disease.