Factors associated with delirium among survivors of acute respiratory distress syndrome: a nationwide cohort study.

BACKGROUND: The prevalence of delirium, its associated factors, and its impact on long-term mortality among survivors of acute respiratory distress syndrome (ARDS) is unclear. METHODS: Since this was a population-based study, data were extracted from the National Health Insurance database in South Korea. All adults who were admitted to intensive care units with a diagnosis of ARDS between January 1, 2010, and December 31, 2019, and who survived for ≥ 60 days were included. The International Statistical Classification of Diseases and Related Health Problems, tenth revision code of delirium (F05) was used to extract delirium cases during hospitalization. RESULTS: A total of 6809 ARDS survivors were included in the analysis, and 319 patients (4.7%) were diagnosed with delirium during hospitalization. In the multivariable logistic regression analysis after covariate adjustment, male sex (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.23, 2.08; P < 0.001), longer duration of hospitalization (OR 1.02, 95% CI 1.01, 1.03; P < 0.001), neuromuscular blockade use (OR 1.50, 95% CI 1.12, 2.01; P = 0.006), benzodiazepine (OR 1.55, 95% CI 1.13, 2.13; P = 0.007) and propofol (OR 1.48, 95% CI 1.01, 2.17; P = 0.046) continuous infusion, and concurrent depression (OR 1.31, 95% CI 1.01, 1.71; P = 0.044) were associated with a higher prevalence of delirium among ARDS survivors. In the multivariable Cox regression analysis after adjustment for covariates, the occurrence of delirium was not significantly associated with 1-year all-cause mortality, when compared to the other survivors who did not develop delirium (hazard ratio: 0.85, 95% CI 1.01, 1.71; P = 0.044). CONCLUSIONS: In South Korea, 4.7% of ARDS survivors were diagnosed with delirium during hospitalization in South Korea. Some factors were potential risk factors for the development of delirium, but the occurrence of delirium might not affect 1-year all-cause mortality among ARDS survivors.

Quality of Life and Long-Term Mortality Among Survivors of Extracorporeal Membrane Oxygenation: A Nationwide Cohort Study in South Korea.

OBJECTIVES: The quality of life after extracorporeal membrane oxygenation therapy has emerged as an important issue for extracorporeal membrane oxygenation survival; however, its association with long-term prognosis has not been identified. We investigated the changes in the quality of life after extracorporeal membrane oxygenation among the survivors and examine the association between a worse quality of life and 3-year all-cause mortality. DESIGN: This was a population-based cohort study. SETTING: Data were obtained from the National Health Insurance Service database in South Korea. PATIENTS: Adult individuals (≥ 18 yr old) who received extracorporeal membrane oxygenation therapy from 2006 to 2017 were included. Extracorporeal membrane oxygenation survivors were defined as patients who had survived for 1-year after the initiation of extracorporeal membrane oxygenation therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The income level, employment status, and registered disability were examined before and 1-year after extracorporeal membrane oxygenation therapy. The decreased income level, job loss, and newly acquired disability were considered as change in the quality of life among extracorporeal membrane oxygenation survivors. A total of 5,821 adult extracorporeal membrane oxygenation survivors were included in the final analysis, and 2,959 patients (50.8%) experienced quality of life change. Specifically, 1,782 patients (30.6%) experienced a decrease in income, 682 (11.7%) lost their jobs, and 1,540 (26.5%) had a new disability within 1-year after extracorporeal membrane oxygenation therapy. In the multivariable Cox regression model, newly acquired disability was associated with 2.31-fold higher 3-year all-cause mortality among extracorporeal membrane oxygenation survivors (hazard ratio, 2.31; 95% CI, 1.79-2.97; p < 0.001), while job loss (p = 0.180) and decreased income (p = 0.993) were not associated with the 3-year all-cause mortality. CONCLUSIONS: At 12 months after extracorporeal membrane oxygenation therapy, nearly half survivors experienced quality of life worsening such as unemployment, decreased income, and new disability. Additionally, among the three factors, acquiring a new disability might significantly increase the 3-year mortality. This is the first study to report the association between changes in the quality of life and long-term prognosis in extracorporeal membrane oxygenation survivors.

Long-term cognitive and psychiatric outcomes of acute respiratory distress syndrome managed with Extracorporeal Membrane Oxygenation.

BACKGROUND: Cognitive dysfunction is often reported in patients who have experienced acute respiratory distress syndrome (ARDS). Extra Corporeal Membrane Oxygenation (ECMO) therapy is increasingly used to manage ARDS patients in ICU, transforming survival rates. However, few studies have examined cognitive outcomes. METHODS: We examined self-reported cognitive complaints, psychiatric outcomes and neuropsychological test performance in survivors of severe hypoxaemia managed with VV-ECMO, at 18-24 month follow-up, compared with a group of healthy controls. RESULTS: Over 70% of ECMO-treated patients (N = 46) complained of difficulty in at least one aspect of cognition on self-report measures (study 1). However, a much lower frequency of cognitive impairment was found on formal neuropsychological testing (study 2). Mean neuropsychological test scores of the ECMO group (N = 24) did not significantly differ from healthy controls (N = 23) after controlling for depression. Less than 30% of ECMO-treated patients showed impairments in anterograde memory, and deficits on general IQ or executive function were seen in <17% of patients. However, we observed high levels of self-reported anxiety and depression in the ECMO-treated patients. CONCLUSIONS: Cognitive outcomes in ECMO-treated patients were generally good, with preserved neuropsychological function in the majority of patients, despite severe hypoxaemia and high rates of self-reported difficulties. However, we saw high levels of mental health symptoms in these patients, highlighting a need for psychological support.

Quality of life following adult veno-venous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been used successfully for the past decade in adult patients with acute respiratory distress syndrome (ARDS) refractory to conventional ventilatory support. However, knowledge of the health-related quality of life (HRQoL) in VV-ECMO patients is still limited. Thus, this study aimed to provide a comprehensive overview of the HRQoL following VV-ECMO support in ARDS patients. METHODS: A systematic search was performed on PubMed and Web of Science databases from January 1st, 2009 to October 19th, 2020. Studies reporting on HRQoL following VV-ECMO for ARDS in adults were included. Two authors independently selected studies, extracted data, and assessed methodological quality. RESULTS: Eight studies were eligible for inclusion, consisting of seven observational studies and one randomized controlled trial (total N = 441). All eight studies had a quantitative design and reported 265 VV-ECMO survivors to have a reduced HRQoL compared to a generally healthy population. Follow-up time varied between six months to three years. Additionally, only four studies (total N = 335) compared the HRQoL of VV-ECMO (N = 159) to conventionally treated survivors (N = 176), with one study showing a significantly better HRQoL in VV-ECMO survivors, while three studies were stating comparable HRQoL across groups. Notably, most survivors in these studies appeared to experience varying degrees of anxiety, depression, and post-traumatic stress disorder (PTSD). CONCLUSIONS: ARDS survivors supported by VV-ECMO have a decline in HRQoL and suffered from physical and psychological impairments. This HRQoL reduction is comparable or even better to the HRQoL in conventionally treated ARDS survivors.

Dyspnea, Acute Respiratory Failure, Psychological Trauma, and Post-ICU Mental Health: A Caution and a Call for Research.

Dyspnea is an uncomfortable sensation with the potential to cause psychological trauma. Patients presenting with acute respiratory failure, particularly when tidal volume is restricted during mechanical ventilation, may experience the most distressing form of dyspnea known as air hunger. Air hunger activates brain pathways known to be involved in posttraumatic stress disorder (PTSD), anxiety, and depression. These conditions are considered part of the post-intensive care syndrome. These sequelae may be even more prevalent among patients with ARDS. Low tidal volume, a mainstay of modern therapy for ARDS, is difficult to avoid and is likely to cause air hunger despite sedation. Adjunctive neuromuscular blockade does not prevent or relieve air hunger, but it does prevent the patient from communicating discomfort to caregivers. Consequently, paralysis may also contribute to the development of PTSD. Although research has identified post-ARDS PTSD as a cause for concern, and investigators have taken steps to quantify the burden of disease, there is little information to guide mechanical ventilation strategies designed to reduce its occurrence. We suggest such efforts will be more successful if they are directed at the known mechanisms of air hunger. Investigation of the antidyspnea effects of sedative and analgesic drugs commonly used in the ICU and their impact on post-ARDS PTSD symptoms is a logical next step. Although in practice we often accept negative consequences of life-saving therapies as unavoidable, we must understand the negative sequelae of our therapies and work to minimize them under our primary directive to "first, do no harm" to patients.

User-Perceived Negative Respiratory Symptoms Associated with Electronic Cigarette Use.

INTRODUCTION: Electronic cigarettes (ECIGs) expose users to an aerosol containing chemicals, which could affect the respiratory system negatively. This study examined negative respiratory symptoms associated with ECIG use. METHODS: In 2019, adult current ECIG users from 24 US states who reported experiencing negative respiratory symptoms from ECIG use (n = 49; 44.9% women; mean age = 35.2, SD = 11.5) completed an online survey and brainstormed statements that completed the prompt: "A specific negative effect or symptom related to my breathing, nose, mouth, throat, or lungs that I have experienced from vaping/using my e-cigarette is..." Participants sorted the final list of 56 statements into groups of similar content and rated statements on how true they were for them. Multidimensional scaling analysis identified thematic clusters. RESULTS: Eight ECIG use respiratory symptom clusters identified in analysis included Mucus and Congestion, Fatigue, Throat Symptoms, Breathing Problems, Mouth Symptoms, Chest Symptoms, Illness Symptoms, and Nose and Sinus Symptoms. Highly rated (ie, most common) symptoms included dry throat or mouth, fatigue during physical activity, coughing, shortness of breath, excessive phlegm, and bad taste in mouth. Mean cluster ratings did not differ based on lifetime cigarette smoking status (100 lifetime cigarettes smoked), but current cigarette smokers (ie, dual users) rated the Fatigue, Breathing Problems, Mucus and Congestion, and Nose and Sinus Symptoms clusters higher than noncurrent cigarette smokers. CONCLUSIONS: Participant-identified respiratory symptoms perceived to be ECIG related, many similar to cigarette smoking symptoms. Future research should assess if these symptoms are associated with other negative health outcomes. IMPLICATIONS: ECIG use exposes users to chemicals that may have negative health impacts on the respiratory system. Limited research has examined the broad range of negative respiratory symptoms associated with e-cigarette use. This study identified that ECIG-cigarette users perceive their ECIG use to be associated with negative respiratory symptoms. Many e-cigarette user-reported negative respiratory symptoms are similar to those associated with cigarette smoking, though some appear unique to e-cigarette use. Future research should continue to monitor respiratory symptoms reported by ECIG users and whether these are associated with health outcomes over time.

Influence of quality of intensive care on quality of life/return to work in survivors of the acute respiratory distress syndrome: prospective observational patient cohort study (DACAPO).

BACKGROUND: Significant long-term reduction in health-related quality of life (HRQoL) is often observed in survivors of the acute respiratory distress syndrome (ARDS), and return to work (RtW) is limited. There is a paucity of data regarding the relationship between the quality of care (QoC) in the intensive care unit (ICU) and both HRQoL and RtW in ARDS survivors. Therefore, the aim of our study was to investigate associations between indicators of QoC and HRQoL and RtW in a cohort of survivors of ARDS. METHODS: To determine the influence of QoC on HRQoL and RtW 1 year after ICU-discharge, ARDS patients were recruited into a prospective multi-centre patient cohort study and followed up regularly after discharge. Patients were asked to complete self-report questionnaires on HRQoL (Short Form 12 physical component scale (PCS) and mental component scale (MCS)) and RtW. Indicators of QoC pertaining to volume, structural and process quality, and general characteristics were recorded on ICU level. Associations between QoC indicators and HrQoL and RtW were investigated by multivariable linear and Cox regression modelling, respectively. B values and hazard ratios (HRs) are reported with corresponding 95% confidence intervals (CIs). RESULTS: 877 (of initially 1225 enrolled) people with ARDS formed the DACAPO survivor cohort, 396 were finally followed up to 1 year after discharge. The twelve-month survivors were characterized by a reduced HRQoL with a greater impairment in the physical component (Md 41.2 IQR [34-52]) compared to the mental component (Md 47.3 IQR [33-57]). Overall, 50% of the patients returned to work. The proportion of ventilated ICU patients showed significant negative associations with both 12 months PCS (B = - 11.22, CI -20.71; - 1,74) and RtW (HR = 0,18, CI 0,04;0,80). All other QoC indicators were not significantly related to outcome. CONCLUSIONS: Associations between ICU QoC and long-term HrQoL and RtW were weak and largely non-significant. Residual confounding by case mix, treatment variables before or during ICU stay and variables pertaining to the post intensive care period (e.g. rehabilitation) cannot be ruled out. TRIAL REGISTRATION: Clinicaltrials.govNCT02637011. (December 22, 2015, retrospectively registered).

Association Between Participant Contact Attempts and Reports of Being Bothered in a National, Longitudinal Cohort Study of ARDS Survivors.

BACKGROUND: Participant retention is a major challenge in clinical research, especially in studies with multiple, longitudinal research assessments. Despite the importance of retention methods, there is little empirical research on how cohort retention efforts are perceived by study participants. RESEARCH QUESTION: To evaluate the association between the number of attempts undertaken to contact participants for research assessments in a longitudinal cohort study and participants' feeling of being bothered regarding such contact attempts. STUDY DESIGN AND METHODS: Secondary analysis of 315 ARDS survivors participating in a prospective study using comprehensive strategies for participant follow-up at 6 and 12 months that achieved > 95% participant retention. After completing a 242-question research assessment lasting 20 to 40 min, participants were surveyed for feedback. RESULTS: At 6 and 12 months, only 5% and 8% of participants, respectively, reported being bothered "more than a little bit" by the study contact attempts, with an OR of 1.06 (95% CI, 1.02-1.10) for each contact attempt. Participants' mental health symptoms at follow-up assessment were not associated with reports of being bothered. INTERPRETATION: Comprehensive cohort retention efforts can achieve > 95% retention rates in a national longitudinal study, with most participants reporting little or no bother by contact attempts. Despite a high frequency of mental health symptoms in this population, such symptoms were not associated with participant feedback regarding contact attempts. Careful training of research staff may be important in achieving such results.

The quality of acute intensive care and the incidence of critical events have an impact on health-related quality of life in survivors of the acute respiratory distress syndrome - a nationwide prospective multicenter observational study.

Background: Initial treatment (ventilator settings, rescue therapy, supportive measures), and prevention of critical events improve survival in ARDS patients, but little data exists on its effect on health-related quality of life (HRQOL) and return to work (RtW) in survivors. We analyzed the association of the intensity of treatment at ARDS onset and the incidence of critical events on HRQOL and RtW a year after ICU discharge. Methods: In a prospective multi-centre cohort study, the intensity of treatment and the incidence of critical events were determined at 61 ICUs in Germany. At 3, 6, and 12 months, 396 survivors reported their HRQOL (Short-Form 12) and RtW. The parameters of the intensity of acute management (lung protective ventilation, prone position, hemodynamic stabilization, neuromuscular blocking agents), and critical events (hypoxemia, hypoglycemia, hypotension) were associated with HRQOL and RtW. Results: Patients ventilated at ARDS onset with a low tidal volume (VT≤7 ml/kg) had higher arterial carbon dioxide levels (PaCO2=57.5±17 mmHg) compared to patients ventilated with VT>7ml/kg (45.7±12, p=0.001). In a multivariate adjusted dichotomized analysis, a better mental 3-month SF-12 was observed in the higher VT-group (mean 43.1±12) compared to the lower VT-group (39.5±9, p=0.042), while a dichotomized analysis for driving pressures (≤14 mbar vs >14 mbar) did not show any difference neither in PaCO2 levels nor in HRQOL parameters. A decrease in the mental (6-month: 40.0±11 vs 44.8±13, p=0.038) and physical SF-12 (12-month: 38.3±11 vs 43.0±13, p=0.015) was reported from patients with hypoglycemia (blood glucose <70 mg/dl) compared to those without hypoglycemic episodes. More frequent vasopressor use with mean arterial pressure ≥65 mmHg was associated with an impaired physical SF-12 (6-month: 38.8±10) compared to less vasopressor use (43.0±11, p=0.019). Conclusions: In acute management of ARDS, a lower VT strategy associated with hypercapnia, as well as the frequent usage of catecholamines and the management of blood glucose may influence short-term HRQOL of survivors. The awareness of these findings is of clinical importance for the acute and post-ICU care.

Long-Term Quality of Life After Extracorporeal Membrane Oxygenation in ARDS Survivors: Systematic Review and Meta-Analysis.

PURPOSE: Extracorporeal membrane oxygenation (ECMO) is an increasingly prevalent treatment for acute respiratory failure (ARF). To evaluate the impact of ECMO support on long-term outcomes for critically ill adults with ARF. METHODS: We searched electronic databases 1948 through to November 30 2016; selected controlled trials or observational studies of critically ill adults with acute respiratory distress syndrome, examining long-term morbidity specifically health-related quality of life (HRQL); 2 authors independently selected studies, extracted data, and assessed methodological quality. ANALYSIS: Of the 633 citations, 1 randomized controlled trial and 5 observational studies met the selection criteria. Overall quality of observational studies was moderate to high (mean score on Newcastle-Ottawa scale, 7.2/9; range, 6-8). In 3 studies (n = 245), greater decrements in HRQL were seen for survivors of ECMO when compared to survivors of conventional mechanical ventilation (CMV) as measured by the Short Form 36 (SF-36) scores ([ECMO-CMV]: 5.40 [95% confidence interval, CI, 4.11 to 6.68]). As compared to CMV survivors, those who received ECMO experienced significantly less psychological morbidity (2 studies; n = 217 [ECMO-CMV]: mean weighted difference [MWD], -1.31 [95% CI, -1.98 to -0.64] for depression and MWD, -1.60 [95% CI, -1.80 to -1.39] for anxiety). CONCLUSIONS: Further studies are required to confirm findings and determine prognostic factors associated with more favorable outcomes in survivors of ECMO.

Stressors and strains of next of kin of patients with ARDS in intensive care: A qualitative interview study using a stress-strain approach.

OBJECTIVES: This study aims to explore and analyse the stressors and strains of next of kin of acute respiratory distress syndrome (ARDS) patients during their stay in the intensive care unit utilising the stressors and strain approach as a theoretical framework. METHODS: Data collection was performed as semi-standardised qualitative interviews. 35 families of patients with ARDS were approached when visiting the intensive care unit. Participants were recruited until thematic saturation was reached; finally, 17 persons (age ranging from 26 to 71 years, nine women) took part. Systematic content analysis was conducted on the theoretical foundations of the stressors and strain approach. FINDINGS: Numerous stressors were identified; they can be divided into three main categories: in relation to organising the visit, occurring during the visit and arising at home. These stressors were reported highly consistently throughout participants. However, the strains resulting from these stressors were varying in manifestation and level. CONCLUSIONS: This study explores the manifold stressors and strains of next of kin of a critically ill patient. Some stressors are inherent to the life-threatening condition of a family member; others arise from the health care system and could be modified. The level of strain experienced depends on social support, individual coping skills and life circumstances.

Screening for posttraumatic stress disorder in ARDS survivors: validation of the Impact of Event Scale-6 (IES-6).

BACKGROUND: Posttraumatic stress disorder (PTSD) symptoms are common in acute respiratory distress syndrome (ARDS) survivors. Brief screening instruments are needed for clinical and research purposes. We evaluated internal consistency, external construct, and criterion validity of the Impact of Event Scale-6 (IES-6; 6 items) compared to the original Impact of Event Scale-Revised (IES-R; 22 items) and to the Clinician Administered PTSD Scale (CAPS) reference standard evaluation in ARDS survivors. METHODS: This study is a secondary analysis from two independent multi-site, prospective studies of ARDS survivors. Measures of internal consistency, and external construct and criterion validity were evaluated. RESULTS: A total of 1001 ARDS survivors (51% female, 76% white, mean (SD) age 49 (14) years) were evaluated. The IES-6 demonstrated internal consistency over multiple time points up to 5 years after ARDS (Cronbach's alpha = 0.86 to 0.91) and high correlation with the IES-R (0.96; 95% confidence interval (CI): 0.94 to 0.97). The IES-6 demonstrated stronger correlations with related constructs (e.g., anxiety and depression; |r| = 0.32 to 0.52) and weaker correlations with unrelated constructs (e.g., physical function and healthcare utilization measures (|r| = 0.02 to 0.27). Criterion validity evaluation with the CAPS diagnosis of PTSD in a subsample of 60 participants yielded an area under receiver operating characteristic curve (95% CI) of 0.93 (0.86, 1.00), with an IES-6 cutoff score of 1.75 yielding 0.88 sensitivity and 0.85 specificity. CONCLUSIONS: The IES-6 is reliable and valid for screening for PTSD in ARDS survivors and may be useful in clinical and research settings.