Non-intubated Patients Research Articles

Examining Historical Data to Inform Future Preparedness: Systematic Review of the Effects of Prone Positioning on Oxygen Levels in Nonintubated COVID-19 Patients

Abstract Over time, there has been a significant increase in the utilization of prone positioning (PP) as a strategy to improve oxygen levels in patients requiring mechanical ventilation for the management of acute respiratory distress syndrome. PP has emerged as a potential intervention for enhancing oxygenation in nonintubated patients with COVID-19. The current systematic review aims to assess existing evidence regarding the impact of PP on oxygen parameters in this patient population. Understanding the effectiveness and possible advantages of PP in optimizing oxygenation could contribute to enhanced management strategies for COVID-19 cases, particularly those that do not require invasive mechanical ventilation. Comprehensive search was conducted using electronic databases to identify the relevant studies, covering the period of 2019–2023. A two-part tool was employed to address five specific domains alongside other potential biases. Quality assessment of diagnostic accuracy studies was undertaken using a risk of bias. In a present systematic review, 15 studies were included. The findings suggest that PP had a notable influence on oxygen parameters. The PP was a beneficial intervention for nonintubated patients of COVID-19 in terms of improving oxygen parameters. The evidence suggests that PP can contribute to enhanced oxygenation in patients. Further research is necessary for a better understanding of optimal techniques, patient selection criteria, and long-term outcomes linked with PP.

Awake prone positioning and ventilation distribution as assessed by electric impedance tomography in patients with non-COVID-19 acute respiratory failure: A prospective physiology study

BackgroundAwake prone positioning (APP) can reportedly reduce the need for intubation and help to improve the prognosis of patients with acute hypoxemic respiratory failure (AHRF) infected with COVID-19. However, its physiological mechanism remains unknown. In this study, we evaluated the effect of APP on lung ventilation in patients with moderate-to-severe AHRF in an attempt to better understand the effects on ventilation distribution and to prevent intubation in non-intubated patients. MethodsThe prospective study was performed in the Department of Critical Care Medicine at Shanghai General Hospital, China, from January 2021 to November 2022. The study included patients with AHRF (partial pressure of oxygen [PaO2]/inspired oxygen concentration [FiO2] <200 mmHg or oxygen saturation [SpO2]/FiO2 <235) treated with high-flow nasal oxygen. Electrical impedance tomography (EIT) measurements including center of ventilation (COV), global inhomogeneity (GI) index, and regional ventilation delay (RVD) index were performed in the supine position (T0), 30 min after the start of APP (T1), and at 30 min returning to supine position after the APP (T2). Clinical parameters like SpO2, respiratory rate (RR), FiO2, heart rate (HR), and ROX (the ratio of SpO2 as measured by pulse oximetry/FiO2 to RR) were also recorded simultaneously at T0, T1, and T2. To evaluate the effect of the time points on the variables, Mauchly's test was performed for sphericity and repeated measures analysis of variance was applied with Bonferroni's post hoc multiple comparisons. ResultsTen patients were enrolled. The PaO2/FiO2 ratio was (111.4±33.4) mmHg at the time of recruitment. ROX showed a significant increase after initiation of APP {median (interquartile range [IQR]): T0: 7.5 (6.0–10.1) vs. T1: 7.6 (6.4–9.3) vs. T2: 8.3 (7.2–11.0), P=0.043}. RR (P=0.409), HR (P=0.249), and SpO2/FiO2 (P=0.103) did not change significantly during prone positioning (PP). The COV moved from the ventral area to the dorsal area (T0: [48.8±6.2] % vs. T1: [54.8±6.8] % vs. T2: [50.3±6.1] %, P=0.03) after APP. The GI decreased significantly after APP (T0: median=42.7 %, [IQR: 38.3–47.5] % vs. T1: median=38.2 %, [IQR: 34.6–50.7] % vs. T2: median=37.4 %, [IQR: 34.2–41.4] %, P=0.049). RVD (P=0.794) did not change after APP. ConclusionsAPP can improve ventilation distribution and homogeneity of lung ventilation as assessed by EIT in non-intubated patients with AHRF.Trail Registration Chinese Clinical Trial Registry Identifier: ChiCTR2000035895.

Adverse Effects Associated With Multimodal Analgesic Regimens in Critically Ill, Nonintubated Patients: A Systematic Review and Meta-Analysis

Objective: To evaluate the safety of utilizing multimodal analgesic regimens in critically ill, nonintubated patients. Data Sources: A systematic review was conducted using Embase, MEDLINE, Cochrane, SciELO, Web of Science, and the Korean Journal Index. Clinical trials of critically ill, nonintubated patients that contained complete safety outcomes date, including the incidence of specific adverse drug effects (ADE) associated with a multimodal analgesic medication or regimen, were included. Study Selection and Data Extraction: The primary outcome was the incidence of adverse drug effects associated with multimodal analgesics in comparison to standard-of-care analgesic strategies in our patient population. The secondary outcome was a subgroup analysis of adverse drug effect by type and by medication. Data Synthesis: 10 trials were included in this systematic review, of which 6 were randomized control trials that were evaluated in the meta-analysis. There was no statistically significant difference with respect to the primary outcome (mean difference = −0.11, P = 0.31, 95% CI = [−0.35, 0.13]). The subgroup analysis, which was conducted on randomized clinical control trials that documented a single adjunctive analgesic rather than a multimodal regimen, was stratified by the type of adverse effect encountered and the medication in question. There were no statistically significant findings regarding the incidence of specific ADE. Nonrandomized data included in this study support these findings. Conclusions: While concerns of the additive deleterious adverse effects commonly encountered in polypharmacy are valid, our findings support the use of multimodal analgesic regimens in the provision of analgesic in critically ill, nonintubated patients.

Evaluation of Coagulation Disorders in Intubated and Non-Intubated Patients with Covid-19 Diagnosis in The Intensive Care unit

Objective: It is known that the need for invasive mechanical ventilation due to severe respiratory failure develops in COVID-19 patients followed in the intensive care unit. It has been reported in the literature that coagulopathy seen during COVID-19 disease is an important cause of mortality and morbidity. Our aim in our study was to evaluate coagulation disorders developing between intubated and non-intubated patients. Method: The data of 812 patients diagnosed with COVID-19 in the Intensive Care Unit, between March 2020 and September 2021 were retrospectively analyzed. The patients were divided into two groups according to the need for invasive mechanical ventilation. Demographic characteristics, laboratory values at the time of diagnosis, coagulopathy development status and survival of the patients were investigated. Results: Of the 812 patients included in the study, 459 (56.5%) were male. The mean age was 66,4 ± 15,2. 257 (31.7%) of the patients received invasive mechanical ventilation support. Coagulopathy was detected in 146 (56.8%) of these patients. Distribution of coagulopathy in intubated patients; 26% Disseminated Intravascular Coagulation, 17.9% Acute Coronary Syndrome, 10.5% Hemorrhage (inside or outside the body), 5.4% Pulmonary Embolism, 5% Heparin-Induced Thrombocytopenia, 3.5% Ischemic Stroke, 1.9% Hemorrhagic Stroke and 0.8% found as Deep Vein Thrombosis. We found that 32% of the patients who were not intubated developed coagulopathy, and this difference was statistically significant (p

Severe stroke: prognosis of ventilated patients

Objective. To determine the outcome of patients with severe stroke who required invasive mechanical ventilation. Materials and Methods. A retrospective study including all stroke patients admitted to the ICU during the last 4 years (2020 and 2023). The primary endpoint was ICU mortality. Results. Thirty-five patients, 20 of them male (sex ratio: 1,3), aged 56,7 ± 18,8 [5 - 79] years were included. Stroke was hemorrhagic in 15 patients (42,8%). 30 patients were intubated. Glasgow score before intubation was 7,4 ± 2,7 [5-13]. Arterial hypertension was found in 65,7 % and diabetes in 42,8% of patients. Three patients were on vitamin K antagonist and three others on antiplatelets. Blood glucose on admission was 1.94 ± 0.72 g/l and systolic blood pressure 152 ± 31 mm Hg. Glasgow score was 6.6 ± 1.9 in intubated patients and 12.4 ± 1.7 in non-intubated patients. Tracheostomy was performed in 28.5% and prolonged the length of stay by 25.2 ± 8.3 days (p: 0.005). The case fatality rate for ventilated patients was 93.5%. No patients were managed by the organ and tissue procurement coordinating team. Conclusion. The prognosis of ventilated strokes is extremely poor, raising the question of early diagnosis and medical and neuro-intensive management in the acute phase

Feasibility of veno-arterial extracorporeal life support in awake patients with cardiogenic shock.

This study sought to demonstrate outcomes of veno-arterial extracorporeal life support (VA-ECLS) in non-intubated ("awake") patients with cardiogenic shock, as very few studies have investigated safety and feasibility in this population. This was a retrospective review of 394 consecutive VA-ECLS patients at our institution from 2017 to 2021. We excluded patients cannulated for indications definitively associated with intubation. Patients were stratified by intubation status at time of cannulation and baseline differences were balanced by inverse probability of treatment weighting. The primary outcome was in-hospital mortality while secondary outcomes included adverse events during ECLS and destination at discharge. Out of 135 patients in the final cohort, 79 were intubated and 56 were awake at time of cannulation. All awake patients underwent percutaneous femoral cannulation with technical success of 100% without intubation. Indications for VA-ECLS in awake patients included acute decompensated heart failure (64.3%), pulmonary hypertension or massive pulmonary embolism (12.5%), myocarditis (8.9%), and acute myocardial infarction (5.4%). After adjustment, awake and intubated patients had similar ECLS duration (7 vs 6 days, p = 0.19), in-hospital mortality (39.6% vs 51.7%, p = 0.28), and rates of various adverse events. Intubation status was not a significant risk factor for 90-day mortality (HR [95% CI]: 1.26 [0.64, 2.45], p = 0.51) in multivariable analysis. Heart transplantation (15.1% vs 4.9%) and ventricular assist device (17.4% vs 2.2%) were more common destinations at discharge in awake patients than intubated patients (p = 0.02). Awake VA-ECLS is safe and feasible with comparable outcomes as intubated counterparts in select cardiogenic shock patients.

Prolonged vs shorter awake prone positioning for COVID-19 patients with acute respiratory failure: a multicenter, randomised controlled trial

PurposeAwake prone positioning has been reported to reduce endotracheal intubation in patients with coronavirus disease 2019 (COVID-19)-related acute hypoxemic respiratory failure (AHRF). However, it is still unclear whether using the awake prone positioning for longer periods can further improve outcomes.MethodsIn this randomized, open-label clinical trial conducted at 12 hospitals in China, non-intubated patients with COVID-19-related AHRF were randomly assigned to prolonged awake prone positioning (target > 12 h daily for 7 days) or standard care with a shorter period of awake prone positioning. The primary outcome was endotracheal intubation within 28 days after randomization. The key secondary outcomes included mortality and adverse events.ResultsIn total, 409 patients were enrolled and randomly assigned to prolonged awake prone positioning (n = 205) or standard care (n = 204). In the first 7 days after randomization, the median duration of prone positioning was 12 h/d (interquartile range [IQR] 12–14 h/d) in the prolonged awake prone positioning group vs. 5 h/d (IQR 2–8 h/d) in the standard care group. In the intention-to-treat analysis, intubation occurred in 35 (17%) patients assigned to prolonged awake prone positioning and in 56 (27%) patients assigned to standard care (relative risk 0.62 [95% confidence interval (CI) 0.42–0.9]). The hazard ratio (HR) for intubation was 0.56 (0.37–0.86), and for mortality was 0.63 (0.42–0.96) for prolonged awake prone positioning versus standard care, within 28 days. The incidence of pre-specified adverse events was low and similar in both groups.ConclusionProlonged awake prone positioning of patients with COVID-19-related AHRF reduces the intubation rate without significant harm. These results support prolonged awake prone positioning of patients with COVID-19-related AHRF.

Prone positioning for acute respiratory distress syndrome in adults : Update on the physiological effects, indications and implementation

The prone position is an immediately available and easily implemented procedure that was introduced more than 50 years ago as a method for improvement of gas exchange in patients with acute respiratory distress syndrome (ARDS). In the meantime, a survival advantage could also be shown in patients with severe ARDS, which led to the recommendation of the prone position for treatment of severe ARDS by expert consensus and specialist society guidelines. The continuing coronavirus disease 2019 (COVID-19) pandemic moved the prone position to the forefront of medicine, including the widespread implementation of the prone position for awake, spontaneously breathing nonintubated patients with acute hypoxemic respiratory insufficiency. The survival advantage is possible due to a reduction of the ventilator-associated lung damage. In this article, the physiological effects, data on clinical results, practical considerations and open questions with respect to the prone position are discussed.

Hypoxaemic respiratory failure and awake prone ventilation (HYPER-AP) - Protocol for randomized, controlled clinical trial

BackgroundAwake prone positioning is studied extensively during Covid-19 pandemic, but there is very limited evidence on its utility in acute hypoxic respiratory failure caused by bacterial infections or other causes. The aim of our research is to evaluate the impact of awake prone positioning on outcomes in non-intubated adult patients with acute non-Covid19 hypoxemic respiratory failure. MethodsThis is a multi-center randomized controlled trial (RCT) with a parallel-group design and a 1:1 allocation ratio. Adult patients, admitted to ICU and diagnosed with hypoxemic respiratory failure will be randomly allocated into intervention (awake prone position (APP)) or control group. Our hypothesis is that addition of awake prone positioning to standard oxygen, high flow oxygen therapy and non-invasive ventilation may reduce the need for mechanical ventilation in adult patients diagnosed with acute hypoxemic respiratory failure. Primary outcome is rate of endotracheal intubation; secondary outcomes include intensive care and hospital mortality, duration of mechanical ventilation, length of intensive care and hospital stay and health related quality of life post hospital discharge. Primary and secondary outcomes will be assessed at hospital discharge, 30, 90 days and 1 year following randomisation. ConclusionThe Hyper-AP study will assess the superiority of awake prone positioning versus standard treatment in spontaneously breathing ICU patients diagnosed with hypoxaemic respiratory failure.

Evaluation of the predictors and frequency of silent hypoxemia in COVID-19 patients and the gap between pulse oximeter and arterial blood gas levels: A cross-sectional study.

Silent hypoxemia is when patients do not experience breathing difficulty in the presence of alarmingly low O2 saturation. It could cause rapid deterioration and higher mortality rates among patients, so prompt detection and identifying predictive factors could result in significantly better outcomes. This study aims to document the evidence of silent hypoxemia in patients with COVID-19 and its clinical features. A total of 78 hospitalized, nonintubated patients with confirmed COVID-19 infection were included in this study. Their O2 saturation was measured with a pulse oximeter (PO), and arterial blood gas (ABG) was taken. Demographic and clinical features were recorded. The Borg scale was used to evaluate dyspnea status, and patients with a score of less than two accompanied by O2 saturation of less than 94% were labeled as silent hypoxic. Univariate analysis was utilized to evaluate the correlation between variables and their odds ratio (OR) and 95% confidence interval (CI). Silent hypoxemia was observed in 20 (25.6%) of the participants. The average difference between the PO and ABG methods was 4.36 ± 3.43. Based on regression analysis, dyspnea and respiratory rate demonstrated a statistically significant correlation with the O2 saturation difference between PO and ABG (OR: 2.05; p = 0.026; 95% CI: 0.248-3.847 and OR: 0.144; p = 0.048, 95% CI: 0.001-0.286). Furthermore, the Borg scale (OR: 0.29; p = 0.009; 95% CI: 0.116-0.740) had a significant reverse correlation with silent hypoxia. Silent hypoxemia can be a possible complication that affects some COVID-19 patients. Further care should be bestowed upon the younger population and those with underlying neurological or mental illnesses. Furthermore, the respiratory rate, pulse oximeter, and arterial blood gas O2 levels should be considered alongside each other.

Assessment of continuous low-dose and high-dose burst of inhaled nitric oxide in spontaneously breathing COVID-19 patients: A randomized controlled trial

BackgroundInhaled nitric oxide (iNO) showed to improve oxygenation at low doses by reducing intrapulmonary shunt and to display antiviral properties at high doses. To assess the safety and potential benefits, we designed an exploratory clinical trial comparing low-dose with intermittent high-dose iNO to only intermittent high-dose iNO in hypoxemic COVID-19 patients. MethodsIn this single-center interventional non-inferiority randomized trial (ClinicalTrials.gov, NCT04476992), twenty oxygen-dependent COVID-19 patients were randomly assigned to the high-dose (200 ppm for 30 min) + continuous low-dose (20 ppm) iNO group (iNO200/20) or the high-dose iNO group (iNO200). Methemoglobinemia (MetHb) assessed 48 h after iNO initiation was the primary endpoint. Reverse-transcription polymerase chain reaction for SARS-CoV-2, inflammatory markers during hospitalization, and heart ultrasounds during the iNO200 treatments were evaluated. ResultsMetHb difference between iNO groups remained within the non-inferiority limit of 3 %, indicating comparable treatments despite being statistically different (p-value<0.01). Both groups presented similar SpO2/FiO2 ratio at 48 h (iNO200 vs. iNO200/20 341[334–356] vs. 359 [331–380], respectively, p-value = 0.436). Both groups showed the same time to SARS-CoV-2 negativization, hospital length of stay, and recovery time. iNO-treated patients showed quicker SARS-CoV-2 negativization compared to a similar group of non-iNO patients (HR 2.57, 95%CI 1.04–6.33). During the 228 treatments, iNO200 and iNO200/20 groups were comparable for safety, hemodynamic stability, and respiratory function improvement. ConclusionsiNO200/20 and iNO200 are equally safe in non-intubated patients with COVID-19-induced respiratory failure with regards to MetHb and NO2. Larger studies should investigate whether iNO200/20 leads to better outcomes compared to non-iNO treated patients.

Nutrition therapy in non-intubated patients with acute respiratory failure: a narrative review.

Non-invasive ventilation use is increasing in patients from acute respiratory failure. However, nutritional assessment and medical nutritional therapy are often missed and patients may be frequently underfed. This review evaluates the tools for nutritional screening and assessment, assesses the use of medical nutritional therapy in various techniques of non invasive ventilation and suggested tools to improve this therapy. A review of the literature was performed to evaluate the tools available to define malnutrition and determine the energy needs of patients requiring non invasive ventilation. Energy and protein intake was assessed in 16 recent papers. High Flow Nasal Cannula Oxygen therapy and non invasive ventilation using mask were described and nutritional therapy determined in each condition. A better determination of malnutrition, a more adequate energy requirement and an improved energy and protein administration are required in patients with acute respiratory failure treated with non invasive ventilation.

Assessment of phosphatemia at admission to the intensive care unit to predict mechanical ventilation among patients with acute exacerbation of chronic obstructive pulmonary disease: a retrospective cohort study.

Hypophosphatemia has been reported to impair diaphragmatic function in patients with chronic obstructive pulmonary disease (COPD). However, little is known about the role of dysphosphatemia at admission [plasmatic phosphate concentration at intensive care unit (ICU) admission (T0-Ph)] to the ICU and respiratory outcomes among patients with severe acute COPD exacerbation. We aimed to assess the value of T0-Ph as a predictive factor of invasive mechanical ventilation (MV) during ICU stay. We retrospectively included consecutive patients admitted to the ICU for a severe acute exacerbation of COPD between May 2015 and December 2018. Logistic multivariate regression analysis was performed to identify association between T0-Ph and the need for invasive MV during the ICU stay. We included 198 patients of whom 132 (67%) were male. The median age was 70 [interquartile range (IQR), 61-77] years. Nine (4.5%) patients died in the ICU. Median T0-Ph was significantly higher among patients requiring invasive MV as compared to non-intubated patients [1.23 (IQR, 1.07-1.41) and 1.09 (IQR, 0.91-1.27) mmol/L; P=0.005]. By multivariate analysis, pneumonia [odds ratio (OR) =6.42; 95% confidence interval (CI): 2.78-15.96; P<0.0001) and a history of intubation (OR =3.33; 95% CI: 0.97-11.19; P=0.05) were independently associated with the need for invasive MV, whereas T0-Ph was not (OR =1.75; 95% CI: 0.72-4.44; P=0.22). T0-Ph was significantly higher in patients requiring invasive MV. However, T0-Ph was not associated with the need for invasive MV in multivariate analysis.

Effect of immediate initiation of invasive ventilation on mortality in acute hypoxemic respiratory failure: a target trial emulation

PurposeInvasive ventilation is a fundamental treatment in intensive care but its precise timing is difficult to determine. This study aims at assessing the effect of initiating invasive ventilation versus waiting, in patients with hypoxemic respiratory failure without immediate reason for intubation on one-year mortality.MethodsEmulation of a target trial to estimate the benefit of immediately initiating invasive ventilation in hypoxemic respiratory failure, versus waiting, among patients within the first 48-h of hypoxemia. The eligible population included non-intubated patients with SpO2/FiO2 ≤ 200 and SpO2 ≤ 97%. The target trial was emulated using a single-center database (MIMIC-IV) which contains granular information about clinical status. The hourly probability to receive mechanical ventilation was continuously estimated. The hazard ratios for the primary outcome, one-year mortality, and the secondary outcome, 30-day mortality, were estimated using weighted Cox models with stabilized inverse probability weights used to adjust for measured confounding.Results2996 Patients fulfilled the inclusion criteria of whom 792 were intubated within 48 h. Among the non-invasive support devices, the use of oxygen through facemask was the most common (75%). Compared to patients with the same probability of intubation but who were not intubated, intubation decreased the hazard of dying for the first year after ICU admission HR 0.81 (95% CI 0.68–0.96, p = 0.018). Intubation was associated with a 30-day mortality HR of 0.80 (95% CI 0.64–0.99, p = 0.046).ConclusionThe initiation of mechanical ventilation in patients with acute hypoxemic respiratory failure reduced the hazard of dying in this emulation of a target trial.

Serial invasive hemodynamics and clinical characteristics of patients with shock with and without invasive mechanical ventilation

Abstract Funding Acknowledgements None. Background Invasive mechanical ventilation (IMV) is commonly used in the Cardiac Intensive Care Unit (CICU) in patients with cardiogenic shock (CS). IMV causes hemodynamic changes that may impact outcomes based upon a patient’s profile. Our aim is to characterize the clinical profile and detailed serial hemodynamic parameters in the first 24-hours according to the use of IMV in patients with shock admitted to the CICU. Methods Retrospective analysis of consecutive patients with shock admitted to the CICU at Bellevue Hospital, undergoing pulmonary artery catheter (PAC) placement within the first 24 hours of admission, from February 2022 to June 2023. Clinical characteristics, as well as specific hemodynamic parameters collected and curated at times 0, 6, 12, 18 and 24 hours were from PAC placement compared between patients with and without IMV. Results A total of 101 patients were included (95% with cardiogenic shock), 59 receiving IMV (age 64 ± 15, 24% women) and 42 non-intubated (61 ± 13, 33% women). Non-intubated patients had higher prevalence of hypertension, prior coronary artery disease and heart failure with reduced ejection fraction (HFrEF), while acute coronary syndromes (44%) and cardiac arrest (12%) were more common causes of admission in patients undergoing IMV. Mixed shock predominated in IMV patients (51 vs 17%, p &amp;lt;0.001), whereas cardiogenic shock (CS) was more common in non-intubated patients (83 vs 41%, p &amp;lt;0.01). Patients with acute myocardial infarction CS (AMI-CS) were more likely to undergo IMV, while patients with heart failure CS (HF-CS) were more likely to be non-intubated. Patients undergoing IMV were more likely to have mechanical circulatory support (MCS) and ventricular dilatation compared to non-intubated patients (LVEDD 5.7 cm vs 4.9 cm, p 0.002). Patients undergoing IMV had a higher incidence of severe shock compared to the non-intubated group (31% vs 19% SCAI Shock D), higher lactate levels and greater use of vasoactive drugs (figure 1A). Patients undergoing IMV had significant improvements in cardiac power output (CPO), diastolic blood pressure and systemic vascular resistance (SVR) (figure 1B). Shock severity by SCAI SHOCK classification had a more notable improvement at 24 hours in patients with IMV compared to non-intubated patients (figure 1C), with a non-statistically significant improvement in lactate clearance in the first 24 hours (Figure 1D). Conclusions IMV in patients with CS is more commonly seen in patients with AMI-CS and among those with higher baseline shock severity and greater use of vasoactive medications. IMV is associated with significant improvements in shock severity, CPO and SVR at 24 hours when compared to patients with shock who are not intubated, which could be related to higher use of vasopressors. Further investigations are warranted to understand the impact of IMV on outcomes of patients with CS and how they might vary according to hemodynamic profile.

Evaluation of the effect of Modafinil in the improvement of the level of consciousness in patients with COVID-19 encephalopathy: A randomized controlled trial.

COVID-19 can lead to encephalopathy and loss of consciousness. This double-blinded randomized clinical trial conducted in Tehran, Iran, aimed to assess the potential effectiveness of modafinil in patients with COVID-19-related encephalopathy. Nineteen non-intubated COVID-19 patients with encephalopathy were randomized into two groups: a treatment group receiving crushed modafinil tablets and a placebo group receiving starch powder. Modafinil was administered at a dose of 100 mg every 2 h, reaching a peak dosage of 400 mg. The level of consciousness was assessed using the Glasgow Coma Score (GCS) at multiple time points on the day of medication administration. The trial was registered under IRCT20170903036041N3 on 23/5/2021. The average age in the modafinil and placebo groups was 75.33 and 70 years, respectively. No significant differences were observed between the two groups in terms of chronic conditions, clinical symptoms, or laboratory data. GCS scores were similar between the groups at baseline (p-value = 0.699). After four doses of modafinil, GCS scores were slightly higher in the treatment group, but this difference was not statistically significant (p-value = 0.581). GCS scores after each round of drug administration didn't significantly differ between the treatment and placebo groups (p-value = 0.908). Modafinil exhibited a slight improvement in the level of consciousness among COVID-19 patients with encephalopathy, although this improvement did not reach statistical significance when compared to the control group. Further research with larger sample sizes and longer treatment durations is recommended to explore modafinil's potential benefits in managing altered consciousness in COVID-19 patients.

Body Position Dependent Participation of Abdominal and Thoracic Breathing Movements During the Breathing Cycle

Aims: Both abdominal and thoracic breathing movements play important roles in the mechanics of breathing, participating differently in various body positions with abdominal breathing having a greater role. Recent studies showed that an early proning position of awake, non-intubated patients during the COVID-19 pandemic, even during pregnancy (PMID: 32320506, PMID: 33309507, PMID: 34915799) significantly affected the ventilatory parameters and mortality of SARS-CoV-2 patients. Thus, we hypothesized that in different body positions the participation of abdominal (AB) and thoracic breathing (TB) during the complete respiratory cycle (CRC) is different. To test this, we measured the participation of AB and TB to the CRC in different body positions under resting conditions. Methods: In young participants (N=26) age between 18 and 24 (M=21.3±1.6), changes in abdominal and chest circumferences were measured using plethysmography respiratory belts, during inhalation and exhalation in standing (ST), sitting (SI), supine (SU), prone (PR), and all on fours (AF) body positions. Respiratory frequency was also measured. Results: In different positions, the contribution of AB and TB to CRC were significantly different (F(4,100)=4.999, p=0.004, η2p=0.17). AB was significantly higher than TB in all positions (p&lt;0.001). More specifically, AB gradually increased, while TB gradually decreased in the following order: SU(AB/TB) = 74.8±12.9%/25.2%, ST = 69±16%/31%, PR = 66.8±20.2%/33.2%, SI = 65.5±14.8%/34.5%, AF = 61.1±15.1%/38.9%. A significantly higher value was measured in the SU position compared to AF (p&lt;0.001) and SI (p=0.011) positions; PR and ST positions showed intermediate values, which were not significantly different from those yielded by either of the other positions. Respiratory frequency was similar in different body positions. Conclusions: These data show that different body positions significantly affect the participation of abdominal and thoracic breathing during resting condition, underscoring not only the importance of respiratory distress patients positioning during hospitalization, but its usefulness in developing a respiratory training plan for elite athletes to optimize their physical and mental performance in competitive sports. AK: Ministry of Innovation and Technology (MIT) of Hungary-NRDI TKP2020-NKA-17, TKP2021-EGA-37, and National Research, Development, and Innovation Offce (NKFIH) OTKA K 132596 K_19, and Hungarian Academy of Sciences, Post-Covid 2021-34, and HUN-REN-SU: 02068 of Hungary, JT: ÚNKP-22-4-II-SE-4 (JT), TKP2021-EGA-25. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The evaluation of a non-invasive respiratory monitor in ards patients in supine and prone position

Purpose: The Prone positioning in addition to non invasive respiratory support is commonly used in patients with acute respiratory failure. The aim of this study was to assess the accuracy of an impedance-based non-invasive respiratory volume monitor (RVM) in supine and in prone position. Methods: In sedated, paralyzed and mechanically ventilated patients in volume-controlled mode with acute respiratory distress syndrome scheduled for prone positioning it was measured and compared non-invasively tidal volume and respiratory rate provided by the RVM in supine and, subsequently, in prone position, by maintaining unchanged the ventilatory setting. Results: Forty patients were enrolled. No significant difference was found between measurements in supine and in prone position either for tidal volume (p = 0.795; p = 0.302) nor for respiratory rate (p = 0.181; p = 0.604). Comparing supine vs. prone position, the bias and limits of agreements for respiratory rate were 0.12 bpm (-1.4 to 1.6) and 20 mL (-80 to 120) for tidal volume. Conclusions: The RVM is accurate in assessing tidal volume and respiratory rate in prone compared to supine position. Therefore, the RVM could be applied in non-intubated patients with acute respiratory failure receiving prone positioning to monitor respiratory function.

Evidence of brain metabolism redistribution from neocortex to primitive brain structures in early acute COVID-19 respiratory syndrome

BackgroundNeuropsychiatric sequelae of COVID-19 have been widely documented in patients with severe neurological symptoms during the chronic or subacute phase of the disease. However, it remains unclear whether subclinical changes in brain metabolism can occur early in the acute phase of the disease. The aim of this study was to identify and quantify changes in brain metabolism in patients hospitalized for acute respiratory syndrome due to COVID-19 with no or mild neurological symptoms.ResultsTwenty-three non-intubated patients (13 women; mean age 55.5 ± 12.1 years) hospitalized with positive nasopharyngeal swab test (RT-PCR) for COVID-19, requiring supplemental oxygen and no or mild neurological symptoms were studied. Serum C-reactive protein measured at admission ranged from 6.43 to 189.0 mg/L (mean: 96.9 ± 54.2 mg/L). The mean supplemental oxygen demand was 2.9 ± 1.4 L/min. [18F]FDG PET/CT images were acquired with a median of 12 (4–20) days of symptoms. After visual interpretation of the images, semiquantitative analysis of [18F]FDG uptake in multiple brain regions was evaluated using dedicated software and the standard deviation (SD) of brain uptake in each region was automatically calculated in comparison with reference values of a normal database. Evolutionarily ancient structures showed positive SD mean values of [18F]FDG uptake. Lenticular nuclei were bilaterally hypermetabolic (> 2 SD) in 21/23 (91.3%) patients, and thalamus in 16/23 (69.6%), bilaterally in 11/23 (47.8%). About half of patients showed hypermetabolism in brainstems, 40% in hippocampi, and 30% in cerebellums. In contrast, neocortical regions (frontal, parietal, temporal and occipital lobes) presented negative SD mean values of [18F]FDG uptake and hypometabolism (< 2 SD) was observed in up to a third of patients. Associations were found between hypoxia, inflammation, coagulation markers, and [18F]FDG uptake in various brain structures.ConclusionsBrain metabolism is clearly affected during the acute phase of COVID-19 respiratory syndrome in neurologically asymptomatic or oligosymptomatic patients. The most frequent finding is marked hypermetabolism in evolutionary ancient structures such as lenticular nucleus and thalami. Neocortical metabolism was reduced in up to one third of patients, suggesting a redistribution of brain metabolism from the neocortex to evolutionary ancient brain structures in these patients.

Increasing sweep gas flow reduces respiratory drive and dyspnea in non-intubated veno-arterial ECMO patients - a pilot study.

Data on assessment and management of dyspnea in patients on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock are lacking. We hypothesized that increasing sweep gas flow through the VA-ECMO oxygenator may decrease dyspnea in non-intubated VA-ECMO patients exhibiting clinically significant dyspnea, with a parallel reduction in respiratory drive. Non-intubated, spontaneously breathing, supine patients on VA-ECMO for cardiogenic shock who presented with a visual analog dyspnea scale (dyspnea-VAS) ≥ 40/100 mm were included. Sweep gas flow was increased up to +6 L/min by three steps of +2 L/min each. Dyspnea was assessed with dyspnea-VAS and Multidimensional Dyspnea Profile. The respiratory drive was assessed by the electromyographic activity of the alae nasi and parasternal muscles. We included 21 patients. On inclusion, median dyspnea-VAS was 50 ([interquartile range] 45-60) mm and sweep gas flow was 1.0 L/min (0.5-2.0). An increase in sweep gas flow significantly decreased dyspnea-VAS (50[45-60] at baseline vs 20[10-30] at 6L/min; p<0.001). The decrease in dyspnea was greater for the sensory component of dyspnea (-50%[43-75]) than for the affective and emotional components (-17%[0-25] and -12%[0-17], p<0.001). An increase in sweep gas flow significantly decreased electromyographic activity of the alae nasi and parasternal muscles (-23%[36-10] and -20[41-0], p<0.001). There was a significant correlation between the sweep gas flow and the dyspnea-VAS (r=-0.91 95%CI[-0.94, -0.87]), between the respiratory drive and the sensory component of dyspnea (r=0.29 95%CI[0.13, 0.44]), between the respiratory drive and the affective component of dyspnea (r=0.29 95%CI[0.02, 0.54]) and between the sweep gas flow and the alae nasi and parasternal (r=-0.31 95%CI[-0.44, -0.22] and r=-0.25 95%CI[-0.44, -0.16]). In critically ill patients with VA-ECMO, an increase in sweep gas flow through the oxygenation membrane decreases dyspnea, possibly mediated by a decrease in respiratory drive.