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Humans, Hypercapnia diagnosis, Hypercapnia therapy, Hypercapnia etiology, Carbon Dioxide, Quality of Life, Oxygen therapeutic use, Hypoventilation, Hypoxia, Noninvasive Ventilation adverse effects, Pulmonary Disease, Chronic Obstructive diagnosis, Pulmonary Disease, Chronic Obstructive therapy, Pulmonary Disease, Chronic Obstructive complications, Respiratory Insufficiency diagnosis, Respiratory Insufficiency etiology, and Respiratory Insufficiency therapy

The respiratory system attempts to maintain normal levels of oxygen and carbon dioxide. However, airflow limitation, parenchymal abnormalities and dysfunction of the respiratory pump may be compromised in individuals with advanced COPD, eventually leading to respiratory failure, with reduced arterial oxygen tension (hypoxaemia) and/or increased arterial carbon dioxide tension ( P aCO 2 ; hypercapnia). Hypoxaemia may persist in individuals with severe COPD despite smoking cessation and optimisation of pharmacotherapy. Long-term oxygen therapy (LTOT) can improve survival in those with severe daytime hypoxaemia, whereas those with less severe hypoxaemia may only have improved exercise capacity and dyspnoea. Changes in respiratory physiology that occur during sleep further predispose to hypoxaemia, particularly in individuals with COPD. However, the major cause of hypoxaemia is hypoventilation. Noninvasive ventilation (NIV) may reduce mortality and need for intubation in individuals with COPD and acute hypercapnic respiratory failure. However, NIV may also improve survival and quality of life in individuals with stable, chronic hypercapnia and is now suggested for those with prolonged hypercapnia ( e.g. P aCO 2 >55 mmHg 2-6 weeks after hospital discharge) when clinically stable and after optimisation of medical therapy including LTOT if indicated. Many questions remain about the optimal mode, settings and goal of NIV therapy.
Competing Interests: Conflict of interest: R.L. Owens has received grant NIH/NHLBI R01HL142114 paid to his institution, outside the submitted work. The remaining authors have nothing to disclose.
(Copyright ©The authors 2023.)

Humans, Intensive Care Units, Respiration, Artificial, Oximetry, Noninvasive Ventilation, Respiratory Distress Syndrome, and Respiratory Insufficiency therapy

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at  https://www.biomedcentral.com/collections/annualupdate2023 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from  https://link.springer.com/bookseries/8901 .
(© 2023. Abe et al.)

Humans, Male, Female, Taiwan epidemiology, Sex Characteristics, Hospital Mortality, Retrospective Studies, Treatment Outcome, Extracorporeal Membrane Oxygenation methods, and Respiratory Insufficiency therapy

Background: The impact of sex-related differences in patients receiving extracorporeal membrane oxygenation support (ECMO) support is still inconclusive. This population-based study aimed to investigate sex differences in short- or long-term outcomes in order to improve clinical practice.
Methods: Patients who received ECMO between 2001 to 2017 were identified from the Taiwan National Health Insurance Research Database. Propensity score matching with a 1:1 ratio was conducted in female-to-male groups, to reduce confounding of baseline covariates. Outcomes included in-hospital mortality, all-cause mortality, all-cause readmission, and ECMO-related complications. Logistic regression analysis, Cox proportional hazard model, and join point regression were used to compare sex differences in both short- or long-term outcomes.
Results: In total, 7,010 matched patients from 11,734 ECMO receivers were included for analysis. The use of ECMO increased dramatically in past years, although the proportion of females was still lower than males. There was a decreasing trend of females undergoing ECMO over time. Female patients have lower risks of in-hospital mortality (64.08% in females vs 66.48% in males; P = 0.0352) and ECMO-related complications compared with males. Furthermore, females also had favorable long-term late outcomes such as all-cause mortality (73.35% in females vs 76.98% in males; P = 0.009) and readmission rate (6.99% in females vs 9.19% in males; P = 0.001).
Conclusions: Female patients had more favorable in-hospital and long-term survival outcomes. Despite improvement in modern ECMO technique and equipment, ECMO remains underutilized in eligible female patients. Thus, females should undergo ECMO treatment if available and indicated.
Trial Registration: The institutional review board of Chang Gung Memorial Hospital approved all data usage and the study protocol (registration number: 202100151B0C502; date of registration: 23/08/2021).
(© 2023. The Author(s).)

Humans, Cannula adverse effects, Oxygen Inhalation Therapy, Cross-Sectional Studies, Intensive Care Units, SARS-CoV-2, COVID-19 complications, COVID-19 therapy, Respiratory Insufficiency etiology, Respiratory Insufficiency therapy, and Respiratory Distress Syndrome therapy

Background: High-flow nasal cannula therapy has been shown to be useful in the treatment of patients with acute respiratory failure caused by severe acute respiratory syndrome-coronavirus disease-2. The ROX index can help predict the success of high-flow nasal cannula in coronavirus disease-19-related acute respiratory failure. However, the timing of ROX- index assessment is still unclear to protect the patients from complications due to early or delayed intubation.
Aims: To evaluate the relation between ROX index patterns within the first 48 hours of the therapy and high-flow nasal cannula success rates. The secondary aim was to determine other possible predictors of high-flow nasal cannula failure.
Study Design: A cross-sectional study.
Methods: Patients admitted to the intensive care unit between April 2020 and January 2022 with coronavirus disease-19-related acute respiratory failure and treated with high-flow nasal cannula were included in the study. Patients’ demographics, clinical characteristics and laboratory findings at intensive care unit admission; ROX indices at initiation, 2 nd , 8 th , 12 th , 24 th and 48 th hours of high-flow nasal cannula; and outcomes were recorded.
Results: In the study period, 69 th patients were managed with high-flow nasal cannula for at least 2 hours. While 24 patients (34.7%) were successfully weaned from high-flow nasal cannula, 45 (65.3%) patients failed. Overall mortality at day 28 was 44.9%. ROX indices were lower in the high-flow nasal cannula failure group through the 12 th , 24 th , and 48 th hours of the therapy, no significant change was observed ( P = 0.33). While an overall increase in ROX index patterns were detected in patients weaned from high-flow nasal cannula ( P = 0.002). Pairwise analyses revealed that ROX indexes remain stable during the first 8th hours in both groups, then improved to 12 th hours of the therapy in successfully high-flow nasal cannula-weaned patients.
Conclusion: Dynamic assessments of the ROX indexes could be more suggestive rather than a point assessment to identify patients who would benefit from the high-flow nasal cannula or deteriorate in coronavirus disease-19 related acute respiratory failure.

Humans, Prospective Studies, Pandemics, Intubation, Intratracheal adverse effects, Respiration, Artificial adverse effects, Intensive Care Units, COVID-19, Noninvasive Ventilation, Respiratory Insufficiency therapy, and Respiratory Insufficiency etiology

Background: The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with coronavirus disease 2019 (COVID-19)-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior noninvasive respiratory support on outcomes.
Methods: This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICUs) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of ICU admission. Propensity score matching was used to achieve a balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different time-point (48 h from ICU admission) for early and delayed intubation.
Results: Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After propensity score matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%; p=0.01), ICU mortality (25.7% versus 36.1%; p=0.007) and 90-day mortality (30.9% versus 40.2%; p=0.02) compared with the early intubation group. Very similar findings were observed when we used a 48-h time-point for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth waves, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (HFNC) (n=294) who were intubated earlier. The subgroup of patients undergoing noninvasive ventilation (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h.
Conclusions: In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received HFNC.
Competing Interests: Conflicts of interest: O. Roca discloses a research grant from Hamilton Medical AG; speaker fees from Hamilton Medical AG, Ambu, Fisher & Paykel Ltd and Aerogen Ltd; and nonfinancial research support from Timpel and Masimo. R. Mellado-Artigas reports speaker fees from Medtronic and Fisher & Paykel, all outside the submitted work. The remaining authors declare no conflicts of interest.
(Copyright ©The authors 2023.)

Humans, Technology, Hospitals, Extracorporeal Membrane Oxygenation adverse effects, and Respiratory Insufficiency therapy

Introduction: Extracorporeal membrane oxygenation (ECMO) is primarily used for the supportive treatment of patients suffering from severe cardiopulmonary failure. With the continued development of ECMO technology, the relevant scenarios also extend pre-hospital and inter-hospital. In order to meet the needs of emergency treatment in communities, disaster sites and battlefields, inter-hospital transfer and evacuation; miniaturized and portable ECMO has become a current research hotspot.
Area Covered: The paper first introduces the principle, composition and common modes of ECMO and summarizes the research status of portable ECMO, Novalung and wearable ECMO, analyzes the characteristics and shortcomings of existing equipment. finally, we discussed the focus and development trend of portable ECMO technology.
Expert Opinion: Currently, portable ECMO has many applications in interhospital transport and there are various studies on portable and wearable ECMO devices, but the development of portable ECMO still faces many challenges. In the future, research related to integrated components, rich sensor arrays, Intelligent ECMO system and lightweight technology can make future portable ECMO more suitable for pre-hospital emergency and interhospital transport.

Adult, Humans, Follow-Up Studies, Head Protective Devices, Quality of Life, Noninvasive Ventilation, COVID-19 therapy, Respiratory Insufficiency etiology, and Respiratory Insufficiency therapy

Purpose: To evaluate whether helmet noninvasive ventilation compared to usual respiratory support reduces 180-day mortality and improves health-related quality of life (HRQoL) in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia.
Methods: This is a pre-planned follow-up study of the Helmet-COVID trial. In this multicenter, randomized clinical trial, adults with acute hypoxemic respiratory failure (n = 320) due to coronavirus disease 2019 (COVID-19) were randomized to receive helmet noninvasive ventilation or usual respiratory support. The modified intention-to-treat population consisted of all enrolled patients except three who were lost at follow-up. The study outcomes were 180-day mortality, EuroQoL (EQ)-5D-5L index values, and EQ-visual analog scale (EQ-VAS). In the modified intention-to-treat analysis, non-survivors were assigned a value of 0 for EQ-5D-5L and EQ-VAS.
Results: Within 180 days, 63/159 patients (39.6%) died in the helmet noninvasive ventilation group compared to 65/158 patients (41.1%) in the usual respiratory support group (risk difference - 1.5% (95% confidence interval [CI] - 12.3, 9.3, p = 0.78). In the modified intention-to-treat analysis, patients in the helmet noninvasive ventilation and the usual respiratory support groups did not differ in EQ-5D-5L index values (median 0.68 [IQR 0.00, 1.00], compared to 0.67 [IQR 0.00, 1.00], median difference 0.00 [95% CI - 0.32, 0.32; p = 0.91]) or EQ-VAS scores (median 70 [IQR 0, 93], compared to 70 [IQR 0, 90], median difference 0.00 (95% CI - 31.92, 31.92; p = 0.55).
Conclusions: Helmet noninvasive ventilation did not reduce 180-day mortality or improve HRQoL compared to usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia.
(© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Humans, Oxygen therapeutic use, Oxygen Inhalation Therapy, and Respiratory Insufficiency therapy

Adult, Humans, SARS-CoV-2, Cannula adverse effects, Respiration, Artificial, Risk Factors, Oxygen Inhalation Therapy, COVID-19 complications, COVID-19 therapy, Respiratory Distress Syndrome etiology, Respiratory Distress Syndrome therapy, Noninvasive Ventilation adverse effects, and Respiratory Insufficiency therapy

In a high proportion of patients, infection by COVID-19 progresses to acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation (IMV) and admission to an intensive care unit (ICU). Other devices, such as a high-flow nasal cannula (HFNC), have been alternatives to IMV in settings with limited resources. This study evaluates whether HFNC exposure time prior to IMV is associated with mortality. This observational, analytical study was conducted on a historical cohort of adults with ARDS due to SARS-CoV-2 who were exposed to HFNC and subsequently underwent IMV. Univariate and multivariate logistic regression was used to analyze the impact of HFNC exposure time on mortality, controlling for multiple potential confounders. Of 325 patients with ARDS, 41 received treatment with HFNC for more than 48 h before IMV initiation. These patients had a higher mortality rate (43.9% vs. 27.1%, p: 0.027) than those using HFNC < 48 h. Univariate analysis evidenced an association between mortality and HFNC ≥ 48 h (OR 2.16. 95% CI 1.087-4.287. p: 0.028). Such an association persisted in the multivariable analysis (OR 2.21. 95% CI 1.013-4.808. p: 0.046) after controlling for age, sex, comorbidities, basal severity of infection, and complications. This study also identified a significant increase in mortality after 36 h in HFNC (46.3%, p: 0.003). In patients with ARDS due to COVID-19, HFNC exposure ≥ 48 h prior to IMV is a factor associated with mortality after controlling multiple confounders. Physiological mechanisms for such an association are need to be defined.
(© 2023. The Author(s).)

Humans, Point-of-Care Systems, Respiration, Artificial, Positive-Pressure Respiration, Respiration, Respiratory Distress Syndrome, and Respiratory Insufficiency therapy

Advanced respiratory monitoring involves several mini- or noninvasive tools, applicable at bedside, focused on assessing lung aeration and morphology, lung recruitment and overdistention, ventilation-perfusion distribution, inspiratory effort, respiratory drive, respiratory muscle contraction, and patient-ventilator asynchrony, in dealing with acute respiratory failure. Compared to a conventional approach, advanced respiratory monitoring has the potential to provide more insights into the pathologic modifications of lung aeration induced by the underlying disease, follow the response to therapies, and support clinicians in setting up a respiratory support strategy aimed at protecting the lung and respiratory muscles. Thus, in the clinical management of the acute respiratory failure, advanced respiratory monitoring could play a key role when a therapeutic strategy, relying on individualization of the treatments, is adopted.
(Copyright © 2023, the American Society of Anesthesiologists. All Rights Reserved.)

Humans, Respiration, Artificial adverse effects, Respiration, Artificial methods, Oxygen, COVID-19 therapy, COVID-19 complications, Respiratory Insufficiency complications, Respiratory Insufficiency therapy, and Respiratory Distress Syndrome therapy

Background: High-flow oxygen therapy (HFOT) has been successful in treating acute hypoxic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS). Successful treatment with noninvasive ventilation and avoidance of mechanical ventilation (MV) has been associated with decreased mortality and positive patient outcomes. It is unclear whether the evidence supports the use of HFOT to treat coronavirus disease 2019 (COVID-19)-induced AHRF and ARDS.
Objectives: To determine whether the use of HFOT decreases the need for intubation or decreases mortality compared with MV in patients with AHRF due to COVID-19.
Data Sources: A literature search was conducted in March 2022 using CINAHL, Embase, PubMed, and Scopus bibliographic databases. Ten studies comparing HFOT and MV in COVID-19 respiratory failure met inclusion criteria.
Conclusions: Nine studies found a statistically significant reduction in the need for intubation; eight studies found significantly decreased morality in patients who received HFOT. Study design and methodologies limited the findings.
Implications for Practice: Based on the available evidence, the use of HFOT positively affected mortality and incidence of the need for intubation and MV. Further research needs to be conducted before HFOT is adopted as the standard of care for COVID-19-induced AHRF and ARDS. Nurse practitioners should be informed regarding the various respiratory support modalities and evaluate risk versus benefit when caring for patients with COVID-19-induced AHRF and ARDS.
Competing Interests: Competing interests: The author reports no conflicts of interest.
(Copyright © 2022 American Association of Nurse Practitioners.)

Child, Humans, Quality of Life, Pain, Risk Factors, Stress Disorders, Post-Traumatic diagnosis, Stress Disorders, Post-Traumatic etiology, Stress Disorders, Post-Traumatic psychology, Respiratory Insufficiency diagnosis, Respiratory Insufficiency etiology, and Respiratory Insufficiency therapy

Objectives: To identify risk factors and outcomes associated with a positive post-traumatic stress disorder (PTSD) screen following pediatric acute respiratory failure treated with invasive mechanical ventilation.
Design: Nonprespecified secondary analysis of a randomized clinical trial.
Setting: Thirty-one U.S. PICUs.
Patients: Children in the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) trial (NCT00814099, ClinicalTrials.gov ) over 8 years old who completed PTSD screening 6 months after discharge.
Interventions: RESTORE sites were randomized to a targeted, nurse-directed sedation strategy versus usual care.
Measurements and Main Results: PTSD screening was completed by 102 subjects using the Child Post-Traumatic Stress Disorder Symptom Scale; a score of greater than or equal to 11 was considered screening positive for PTSD. Cognitive status was categorized using Pediatric Cerebral Performance Category; health-related quality of life (HRQL) was evaluated using child-reported Pediatric Quality of Life Inventory, Version 4.0. Thirty-one children (30%) screened positive for PTSD. Children with a positive screen endorsed symptoms in all categories: reexperiencing, avoidance, and hyperarousal. Most endorsed that symptoms interfered with schoolwork ( n = 18, 58%) and happiness ( n = 17, 55%). Screening positive was not associated with RESTORE treatment group. In a multivariable logistic model adjusting for age, sex, and treatment group, screening positive was independently associated with lower median income in the family's residential zip code (compared with income ≥ $80,000; income < $40,000 odds ratio [OR], 32.8; 95% CI, 2.3-458.1 and $40,000-$79,999 OR, 15.6; 95% CI, 1.3-182.8), renal dysfunction (OR 5.3, 95% CI 1.7-16.7), and clinically significant pain in the PICU (OR, 8.3; 95% CI, 1.9-35.7). Children with a positive screen experienced decline in cognitive function and impaired HRQL more frequently than children with a negative screen.
Conclusions: Screening positive for PTSD is common among children following acute respiratory failure and is associated with lower HRQL and decline in cognitive function. Routine PTSD screening may be warranted to optimize recovery.
Competing Interests: Drs. Olszewski, Smith, Asaro, Wypij, Curley, and Watson received support for article research from the National Institutes of Health (NIH). Dr. Smith received funding from the National Institute of Child Health and Human Development (Grant 5T32HD057822-10). Drs. Asaro’s and Watson’s institutions received funding from the NIH. Drs. Wypij’s and Curley’s institutions received funding from the National Heart, Lung, and Blood Institute. Dr. Wypij received funding from the NIH (U01 HL086649). Dr. Curley received funding from the NIH (U01 HL086622). Dr. Dervan has disclosed that she does not have any potential conflicts of interest.
(Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Humans, Hospitalization, Length of Stay, Intensive Care Units, Emergency Service, Hospital, Hospitals, Hospital Mortality, Retrospective Studies, Respiratory Distress Syndrome, and Respiratory Insufficiency therapy

Rationale: We have previously shown that hospital strain is associated with intensive care unit (ICU) admission and that ICU admission, compared with ward admission, may benefit certain patients with acute respiratory failure (ARF). Objectives: To understand how strain-process-outcomes relationships in patients with ARF may vary among hospitals and what hospital practice differences may account for such variation. Methods: We examined high-acuity patients with ARF who did not require mechanical ventilation or vasopressors in the emergency department (ED) and were admitted to 27 U.S. hospitals from 2013 to 2018. Stratifying by hospital, we compared hospital strain-ICU admission relationships and hospital length of stay (LOS) and mortality among patients initially admitted to the ICU versus the ward using hospital strain as a previously validated instrumental variable. We also surveyed hospital practices and, in exploratory analyses, evaluated their associations with the above processes and outcomes. Results: There was significant among-hospital variation in ICU admission rates, in hospital strain-ICU admission relationships, and in the association of ICU admission with hospital LOS and hospital mortality. Overall, ED patients with ARF ( n  = 45,339) experienced a 0.82-day shorter median hospital LOS if admitted initially to the ICU compared with the ward, but among the 27 hospitals ( n  = 224-3,324), this effect varied from 5.85 days shorter (95% confidence interval [CI], -8.84 to -2.86; P  < 0.001) to 4.38 days longer (95% CI, 1.86-6.90; P  = 0.001). Corresponding ranges for in-hospital mortality with ICU compared with ward admission revealed odds ratios from 0.08 (95% CI, 0.01-0.56; P  < 0.007) to 8.89 (95% CI, 1.60-79.85; P  = 0.016) among patients with ARF (pooled odds ratio, 0.75). In exploratory analyses, only a small number of measured hospital practices-the presence of a sepsis ED disposition guideline and maximum ED patient capacity-were potentially associated with hospital strain-ICU admission relationships. Conclusions: Hospitals vary considerably in ICU admission rates, the sensitivity of those rates to hospital capacity strain, and the benefits of ICU admission for patients with ARF not requiring life support therapies in the ED. Future work is needed to more fully identify hospital-level factors contributing to these relationships.

Male, Humans, Brain, Extracorporeal Membrane Oxygenation methods, Respiratory Insufficiency therapy, Lung Diseases, Interstitial, and Lung Transplantation

In Japan, successful cases of a bridge to lung transplantation (BTT) by extracorporeal membrane oxygenation (ECMO) are rare. We present the case of a man in his thirties, diagnosed with interstitial pneumonia 6 years prior and registered for lung transplant 1 year prior due to disease progression despite treatment. Due to the patient's worsening respiratory failure, he was transferred to our hospital for BTT by ECMO. Since long-term management was expected and pulmonary hypertension was present, veno-arterial (V-A) ECMO was conducted using the right atrial blood outflow via the right internal jugular vein and right axillary artery inflow via a vascular graft. After tracheostomy, he was managed as "Awake ECMO". In addition, interprofessional collaboration such as physiotherapist rehabilitation, nurses, and liaison teams prevented muscle weakness and supported the mental aspect. We were able to minimize complications such as severe infections and bleeding. A compatible brain-dead donor was found on day 108 after introducing ECMO, and the patient was transferred to a transplant facility on day 109. The peripheral upper V-A ECMO is one of the configurations suitable for long-term BTT management.
(© 2022. The Japanese Society for Artificial Organs.)

Humans, Retrospective Studies, COVID-19 therapy, Extracorporeal Membrane Oxygenation, and Respiratory Insufficiency therapy

Competing Interests: We declare no competing interests.