Association of analgosedation with psychiatric symptoms and health-related quality of life in ARDS survivors: post hoc analyses of the DACAPO study

Background The acute respiratory distress syndrome (ARDS) is a life-threatening condition with the risk of developing hypoxia and thus requires for invasive mechanical ventilation a long-term analgosedation. Yet, prolonged analgosedation may be a reason for declining health-related quality of life (HRQoL) and the development of psychiatric disorders. Methods We used data from the prospective observational nation‑wide ARDS study across Germany (DACAPO) to investigate the influence of sedation and analgesia on HRQoL and the risk of psychiatric symptoms in ARDS survivors 3, 6 and 12 months after their discharge from the intensive care unit (ICU). HRQoL was measured with the Physical and Mental Component Scale of the Short‑Form 12 Questionnaire (PCS‑12, MCS‑12). The prevalence of psychiatric symptoms (depression and post‑traumatic stress disorder [PTSD]) was assessed using the Patient Health Questionnaire‑9 and the Post‑Traumatic Stress Syndrome‑14. The associations of analgosedation with HRQoL and psychiatric symptoms were investigated by means of multivariable linear regression models. Results The data of 134 ARDS survivors (median age [IQR]: 55 [44–64], 67% men) did not show any significant association between analgosedation and physical or mental HRQoL up to 1 year after ICU discharge. Multivariable linear regression analysis (B [95%‑CI]) yielded a significant association between symptoms of psychiatric disorders and increased cumulative doses of ketamine up to 6 months after ICU discharge (after 3 months: depression: 0.15 [0.05, 0.25]; after 6 months: depression: 0.13 [0.03, 0.24] and PTSD: 0.42 [0.04, 0.80)]). Conclusions Up to 1 year after ICU discharge, analgosedation did not influence HRQoL of ARDS survivors. Prolonged administration of ketamine during ICU treatment, however, was positively associated with the risk of psychiatric symptoms. The administration of ketamine to ICU patients with ARDS should be with caution

Tracheostomy in patients with acute respiratory distress syndrome is not related to quality of life, symptoms of psychiatric disorders or return-to-work: the prospective DACAPO cohort study

Background Acute respiratory distress syndrome (ARDS) is a life-threatening condition that often requires prolonged mechanical ventilation. Tracheostomy is a common procedure with some risks, on the other hand with potential advantages over orotracheal intubation in critically ill patients. This study investigated the association of tracheostomy with health-related quality of life (HRQoL), symptoms of psychiatric disorders and return-to-work of ARDS survivors. Methods Data were collected in the context of the prospective observational German-wide DACAPO study. Clinical and demographic patient data and treatment characteristics were obtained from the participating intensive care units (ICU). HRQoL and return-to-work were assessed using patient-reported questionnaires 3, 6 and 12 months after ICU discharge. HRQoL was measured with the Physical and Mental Component Scale of the Short-Form 12 Questionnaire (PCS-12, MCS-12). The prevalence of psychiatric symptoms (depression and post-traumatic stress disorder [PTSD]) was assessed using the Patient Health Questionnaire-9 and the Post-Traumatic Stress Syndrome-14. Physician-diagnosed anxiety and obsessive-compulsive disorder were recorded by patient self-report in the follow-up questionnaires. The associations of tracheostomy with HRQoL, psychiatric symptoms and return-to-work after 12 months were investigated by means of multivariable linear and logistic regression models. Results Primary 877 ARDS patients (mean +/- standard deviation: 54 +/- 16 years, 68% male) survived and were discharged from ICU. Out of these patients, 478 (54.5%) were tracheotomised during ICU treatment. After 12 months, patient-reported outcomes could be analysed of 388 (44.2%) respondents, 205 with tracheostomy and 183 without. One year after ICU discharge, tracheostomy showed no significant association with physical or mental health-related quality of life (PCS-12: - 0.73 [- 3.96, 2.51]; MCS-12: - 0.71 [- 4.92, 3.49]), symptoms of psychiatric disorders (depression: 0.10 [- 1.43, 1.64]; PTSD: 3.31 [- 1.81, 8.43]; anxiety: 1.26 [0.41, 3.86]; obsessive-compulsive disorder: 0.59 [0.05, 6.68]) or return-to-work (0.71 [0.31, 1.64]) in the multivariable analysis (OR [95%-CI]). Conclusions Up to 1 year after ICU discharge, neither HRQoL nor symptoms of psychiatric disorders nor return-to-work was affected by tracheostomy. Trial registration NCT02637011 (ClinicalTrials.gov, Registered 15 December 2015, retrospectively registered

Immune Responses in Healthy and Allergic Individuals Are Characterized by a Fine Balance between Allergen-specific T Regulatory 1 and T Helper 2 Cells

The mechanisms by which immune responses to nonpathogenic environmental antigens lead to either allergy or nonharmful immunity are unknown. Single allergen-specific T cells constitute a very small fraction of the whole CD4+ T cell repertoire and can be isolated from the peripheral blood of humans according to their cytokine profile. Freshly purified interferon-γ–, interleukin (IL)-4–, and IL-10–producing allergen-specific CD4+ T cells display characteristics of T helper cell (Th)1-, Th2-, and T regulatory (Tr)1–like cells, respectively. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4–secreting T cells in allergic individuals. Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-β as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules. Healthy and allergic individuals exhibit all three allergen-specific subsets in different proportions, indicating that a change in the dominant subset may lead to allergy development or recovery. Accordingly, blocking the suppressor activity of Tr1 cells or increasing Th2 cell frequency enhances allergen-specific Th2 cell activation ex vivo. These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy

Impact of sweep gas flow on extracorporeal CO2 removal (ECCO2R)

Background Veno-venous extracorporeal carbon dioxide (CO2) removal (vv-ECCO2R) is increasingly being used in the setting of acute respiratory failure. Blood flow rates range in clinical practice from 200 mL/min to more than 1500 mL/min, and sweep gas flow rates range from less than 1 to more than 10 L/min. The present porcine model study was aimed at determining the impact of varying sweep gas flow rates on CO2 removal under different blood flow conditions and membrane lung surface areas. Methods Two different membrane lungs, with surface areas of 0.4 and 0.8m2, were used in nine pigs with experimentally-induced hypercapnia. During each experiment, the blood flow was increased stepwise from 300 to 900 mL/min, with further increases up to 1800 mL/min with the larger membrane lung in steps of 300 mL/min. Sweep gas was titrated under each condition from 2 to 8 L/min in steps of 2 L/min. Extracorporeal CO2 elimination was normalized to a PaCO2 of 45 mmHg before the membrane lung. Results Reversal of hypercapnia was only feasible when blood flow rates above 900 mL/min were used with a membrane lung surface area of at least 0.8m2. The membrane lung with a surface of 0.4m2 allowed a maximum normalized CO2 elimination rate of 41 ± 6 mL/min with 8 L/min sweep gas flow and 900 mL blood flow/min. The increase in sweep gas flow from 2 to 8 L/min increased normalized CO2 elimination from 35 ± 5 to 41 ± 6 with 900 mL blood flow/min, whereas with lower blood flow rates, any increase was less effective, levelling out at 4 L sweep gas flow/min. The membrane lung with a surface area of 0.8m2 allowed a maximum normalized CO2 elimination rate of 101 ± 12 mL/min with increasing influence of sweep gas flow. The delta of normalized CO2 elimination increased from 4 ± 2 to 26 ± 7 mL/min with blood flow rates being increased from 300 to 1800 mL/min, respectively. Conclusions The influence of sweep gas flow on the CO2 removal capacity of ECCO2R systems depends predominantly on blood flow rate and membrane lung surface area. In this model, considerable CO2 removal occurred only with the larger membrane lung surface of 0.8m2 and when blood flow rates of ≥ 900 mL/min were used

Low-flow assessment of current ECMO/ECCO2R rotary blood pumps and the potential effect on hemocompatibility

Background Extracorporeal carbon dioxide removal (ECCO2R) uses an extracorporeal circuit to directly remove carbon dioxide from the blood either in lieu of mechanical ventilation or in combination with it. While the potential benefits of the technology are leading to increasing use, there are very real risks associated with it. Several studies demonstrated major bleeding and clotting complications, often associated with hemolysis and poorer outcomes in patients receiving ECCO2R. A better understanding of the risks originating specifically from the rotary blood pump component of the circuit is urgently needed. Methods High-resolution computational fluid dynamics was used to calculate the hemodynamics and hemocompatibility of three current rotary blood pumps for various pump flow rates. Results The hydraulic efficiency dramatically decreases to 5–10% if operating at blood flow rates below 1 L/min, the pump internal flow recirculation rate increases 6–12-fold in these flow ranges, and adverse effects are increased due to multiple exposures to high shear stress. The deleterious consequences include a steep increase in hemolysis and destruction of platelets. Conclusions The role of blood pumps in contributing to adverse effects at the lower blood flow rates used during ECCO2R is shown here to be significant. Current rotary blood pumps should be used with caution if operated at blood flow rates below 2 L/min, because of significant and high recirculation, shear stress, and hemolysis. There is a clear and urgent need to design dedicated blood pumps which are optimized for blood flow rates in the range of 0.5–1.5 L/min

Hemolysis at low blood flow rates: in-vitro and in-silico evaluation of a centrifugal blood pump

Background Treating severe forms of the acute respiratory distress syndrome and cardiac failure, extracorporeal membrane oxygenation (ECMO) has become an established therapeutic option. Neonatal or pediatric patients receiving ECMO, and patients undergoing extracorporeal CO2 removal (ECCO2R) represent low-flow applications of the technology, requiring lower blood flow than conventional ECMO. Centrifugal blood pumps as a core element of modern ECMO therapy present favorable operating characteristics in the high blood flow range (4 L/min–8 L/min). However, during low-flow applications in the range of 0.5 L/min–2 L/min, adverse events such as increased hemolysis, platelet activation and bleeding complications are reported frequently. Methods In this study, the hemolysis of the centrifugal pump DP3 is evaluated both in vitro and in silico, comparing the low-flow operation at 1 L/min to the high-flow operation at 4 L/min. Results Increased hemolysis occurs at low-flow, both in vitro and in silico. The in-vitro experiments present a sixfold higher relative increased hemolysis at low-flow. Compared to high-flow operation, a more than 3.5-fold increase in blood recirculation within the pump head can be observed in the low-flow range in silico. Conclusions This study highlights the underappreciated hemolysis in centrifugal pumps within the low-flow range, i.e. during pediatric ECMO or ECCO2R treatment. The in-vitro results of hemolysis and the in-silico computational fluid dynamic simulations of flow paths within the pumps raise awareness about blood damage that occurs when using centrifugal pumps at low-flow operating points. These findings underline the urgent need for a specific pump optimized for low-flow treatment. Due to the inherent problems of available centrifugal pumps in the low-flow range, clinicians should use the current centrifugal pumps with caution, alternatively other pumping principles such as positive displacement pumps may be discussed in the future

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)

BackgroundSignificant 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.MethodsTo 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).Results877 (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 12months 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.ConclusionsAssociations 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 registrationClinicaltrials.govNCT02637011.(December 22, 2015, retrospectively registered

German-wide prospective DACAPO cohort of survivors of the acute respiratory distress syndrome (ARDS): a cohort profile

Purpose While most research focuses on the association between medical characteristics and residual morbidity of survivors of the acute respiratory distress syndrome (ARDS), little is known about the relation between potentially modifiable intensive care unit (ICU) features and the course of health-related quality of life (HRQoL). Accordingly, the DACAPO study was set up to elucidate the influence of quality of intensive care on HRQoL and return to work (RtW) in survivors of ARDS. The continued follow-up of these former ICU patients leads to the establishment of the DACAPO (survivor) cohort. Participants Sixty-one ICUs all over Germany recruited patients with ARDS between September 2014 and April 2016. Inclusion criteria were: (1) age older than 18 years and (2) ARDS diagnosis according to the ‘Berlin definition’. No further inclusion or exclusion criteria were applied. 1225 patients with ARDS could be included in the DACAPO ICU sample. Subsequently, the 876 survivors at ICU discharge form the actual DACAPO cohort. Findings to date The recruitment of the participants of the DACAPO cohort and the baseline data collection has been completed. The care-related data of the DACAPO cohort reveal a high proportion of adverse events (in particular, hypoglycaemia and reintubation). However, evidence-based supportive measures were applied frequently. Future plans Three months, 6 months and 1 year after ICU admission a follow-up assessment is conducted. The instruments of the follow-up questionnaires comprise the domains: (A) HRQoL, (B) RtW, (C) general disability, (D) psychiatric symptoms and (E) social support. Additionally, an annual follow-up of the DACAPO cohort focusing on HRQoL, psychiatric symptoms and healthcare utilisation will be conducted. Furthermore, several add-on projects affecting medical issues are envisaged

German-wide prospective DACAPO cohort of survivors of the acute respiratory distress syndrome (ARDS): a cohort profile

Purpose While most research focuses on the association between medical characteristics and residual morbidity of survivors of the acute respiratory distress syndrome (ARDS), little is known about the relation between potentially modifiable intensive care unit (ICU) features and the course of health-related quality of life (HRQoL). Accordingly, the DACAPO study was set up to elucidate the influence of quality of intensive care on HRQoL and return to work (RtW) in survivors of ARDS. The continued follow-up of these former ICU patients leads to the establishment of the DACAPO (survivor) cohort. Participants Sixty-one ICUs all over Germany recruited patients with ARDS between September 2014 and April 2016. Inclusion criteria were: (1) age older than 18 years and (2) ARDS diagnosis according to the 'Berlin definition'. No further inclusion or exclusion criteria were applied. 1225 patients with ARDS could be included in the DACAPO ICU sample. Subsequently, the 876 survivors at ICU discharge form the actual DACAPO cohort. Findings to date The recruitment of the participants of the DACAPO cohort and the baseline data collection has been completed. The care-related data of the DACAPO cohort reveal a high proportion of adverse events (in particular, hypoglycaemia and reintubation). However, evidence-based supportive measures were applied frequently. Future plans Three months, 6 months and 1 year after ICU admission a follow-up assessment is conducted. The instruments of the follow-up questionnaires comprise the domains: (A) HRQoL, (B) RtW, (C) general disability, (D) psychiatric symptoms and (E) social support. Additionally, an annual follow-up of the DACAPO cohort focusing on HRQoL, psychiatric symptoms and healthcare utilisation will be conducted. Furthermore, several add-on projects affecting medical issues are envisaged