Inter-rater reliability of descriptors for the classification of mucosal pressure injury: A prospective cross-sectional study.

BACKGROUND: Mucosal pressure injuries (PIs) are usually caused by pressure from essential medical devices. There is no universally accepted criterion for assessment, monitoring, or reporting mucosal PI. Reliable descriptors are vital to benchmark the frequency and severity of this hospital-acquired complication. OBJECTIVES: The objective of this study was to determine whether modified Reaper Oral Mucosa Pressure Injury Scale (ROMPIS) descriptors improved the reliability of mucosal PI assessment. Secondary aims were to explore nurses' knowledge of and attitudes toward mucosal PI. METHODS: A prospective cross-sectional survey was distributed to nurses from two tertiary affiliated intensive care units via REDCap® to capture demographic data, knowledge, attitudes, and inter-rater reliability (IRR) measures. Nurses were randomised at a 1:1 ratio to original or modified ROMPIS descriptors and classified 12 images of mucosal PI. IRR was assessed using percentage agreement, Fleiss' kappa, and intraclass correlation coefficients. RESULTS: The survey response rate was 20.9% (n = 98/468), with 73.5% (n = 72/98) completing IRR measures. Agreement was higher with modified (75%) than original ROMPIS descriptors (69.4%). IRR was fair for the original (κ = 0.30, 95% confidence interval [CI] [0.28, 0.33], z 26.5, p < 0.001) and modified ROMPIS (κ = 0.29, 95% CI [0.26, 0.31], z 25.0, p < 0.001). Intraclass correlation coefficient findings indicated ratings were inconsistent for the original (0.33, 95% CI [0.18, 0.59], F 18.8 (11 df), p < 0.001) and modified ROMPIS (0.31, 95% CI [0.17, 0.57], F 17.6 (11 df), p < 0.001). PI-specific education and risk factor recognition were common. CONCLUSION: Modified descriptors had marginally better agreement. Participants understand management and prevention but need to strengthen their perceived capacity for mucosal PI risk assessment. This work provides a foundation for future benchmarking and a platform from which further research to refine and test descriptors specific to mucosal PI can be generated.

Remi-fent 1-A pragmatic randomised controlled study to evaluate the feasibility of using remifentanil or fentanyl as sedation adjuncts in mechanically ventilated patients.

Objective: To evaluate the feasibility of conducting a prospective randomised controlled trial (pRCT) comparing remifentanil and fentanyl as adjuncts to sedate mechanically ventilated patients. Design: Single-center, open-labelled, pRCT with blinded analysis. Setting: Australian tertiary intensive care unit (ICU). Participants: Consecutive adults between June 2020 and August 2021 expected to receive invasive ventilation beyond the next day and requiring opioid infusion were included. Exclusion criteria were pregnant/lactating women, intubation >12 h, or study-drug hypersensitivity. Interventions: Open-label fentanyl and remifentanil infusions per existing ICU protocols. Outcomes: Primary outcomes were feasibility of recruiting ≥1 patient/week and >90 % compliance, namely no other opioid infusion used during the study period. Secondary outcomes included complications, ICU-, ventilator- and hospital-free days, and mortality (ICU, hospital). Blinded intention-to-treat analysis was performed concealing the allocation group. Results: 208 patients were enrolled (mean 3.7 patients/week). Compliance was 80.6 %. More patients developed complications with fentanyl than remifentanil: bradycardia (n = 44 versus n = 21; p < 0.001); hypotension (n = 78 versus n = 53; p < 0.01); delirium (n = 28 versus n = 15; p = 0.001). No differences were seen in ICU (24.3 % versus 27.6 %,p = 0.60) and hospital mortalities (26.2 % versus 30.5 %; p = 0.50). Ventilator-free days were higher with remifentanil (p = 0.01). Conclusions: We demonstrated the feasibility of enrolling patients for a pRCT comparing remifentanil and fentanyl as sedation adjuncts in mechanically ventilated patients. We failed to attain the study-opioid compliance target, likely because of patients with complex sedative/analgesic requirements. Secondary outcomes suggest that remifentanil may reduce mechanical ventilation duration and decrease the incidence of complications. An adequately powered multicentric phase 2 study is required to evaluate these results.

Comparison of 6-Month Outcomes of Survivors of COVID-19 versus Non-COVID-19 Critical Illness.

Rationale: The outcomes of survivors of critical illness due to coronavirus disease (COVID-19) compared with non-COVID-19 are yet to be established. Objectives: We aimed to investigate new disability at 6 months in mechanically ventilated patients admitted to Australian ICUs with COVID-19 compared with non-COVID-19. Methods: We included critically ill patients with COVID-19 and non-COVID-19 from two prospective observational studies. Patients were eligible if they were adult (age ⩾ 8 yr) and received ⩾24 hours of mechanical ventilation. In addition, patients with COVID-19 were eligible with a positive laboratory PCR test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Measurements and Main Results: Demographic, intervention, and hospital outcome data were obtained from electronic medical records. Survivors were contacted by telephone for functional outcomes with trained outcome assessors using the World Health Organization Disability Assessment Schedule 2.0. Between March 6, 2020, and April 21, 2021, 120 critically ill patients with COVID-19, and between August 2017 and January 2019, 199 critically ill patients without COVID-19, fulfilled the inclusion criteria. Patients with COVID-19 were older (median [interquartile range], 62 [55-71] vs. 58 [44-69] yr; P = 0.019) with a lower Acute Physiology and Chronic Health Evaluation II score (17 [13-20] vs. 19 [15-23]; P = 0.011). Although duration of ventilation was longer in patients with COVID-19 than in those without COVID-19 (12 [5-19] vs. 4.8 [2.3-8.8] d; P < 0.001), 180-day mortality was similar between the groups (39/120 [32.5%] vs. 70/199 [35.2%]; P = 0.715). The incidence of death or new disability at 180 days was similar (58/93 [62.4%] vs. 99/150 [66/0%]; P = 0.583). Conclusions: At 6 months, there was no difference in new disability for patients requiring mechanical ventilation for acute respiratory failure due to COVID-19 compared with non-COVID-19. Clinical trial registered with www.clinicaltrials.gov (NCT04401254).

The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study.

BACKGROUND: There are few reports of new functional impairment following critical illness from COVID-19. We aimed to describe the incidence of death or new disability, functional impairment and changes in health-related quality of life of patients after COVID-19 critical illness at 6 months. METHODS: In a nationally representative, multicenter, prospective cohort study of COVID-19 critical illness, we determined the prevalence of death or new disability at 6 months, the primary outcome. We measured mortality, new disability and return to work with changes in the World Health Organization Disability Assessment Schedule 2.0 12L (WHODAS) and health status with the EQ5D-5LTM. RESULTS: Of 274 eligible patients, 212 were enrolled from 30 hospitals. The median age was 61 (51-70) years, and 124 (58.5%) patients were male. At 6 months, 43/160 (26.9%) patients died and 42/108 (38.9%) responding survivors reported new disability. Compared to pre-illness, the WHODAS percentage score worsened (mean difference (MD), 10.40% [95% CI 7.06-13.77]; p < 0.001). Thirteen (11.4%) survivors had not returned to work due to poor health. There was a decrease in the EQ-5D-5LTM utility score (MD, - 0.19 [- 0.28 to - 0.10]; p < 0.001). At 6 months, 82 of 115 (71.3%) patients reported persistent symptoms. The independent predictors of death or new disability were higher severity of illness and increased frailty. CONCLUSIONS: At six months after COVID-19 critical illness, death and new disability was substantial. Over a third of survivors had new disability, which was widespread across all areas of functioning. Clinical trial registration NCT04401254 May 26, 2020.

Association Between Premorbid Beta-Blocker Exposure and Sepsis Outcomes-The Beta-Blockers in European and Australian/American Septic Patients (BEAST) Study.

OBJECTIVES: To examine the effect of premorbid ß-blocker exposure on mortality and organ dysfunction in sepsis. DESIGN: Retrospective observational study. SETTING: ICUs in Australia, the Czech Republic, and the United States. PATIENTS: Total of 4,086 critical care patients above 18 years old with sepsis between January 2014 and December 2018. INTERVENTION: Premorbid beta-blocker exposure. MEASUREMENTS AND MAIN RESULTS: One thousand five hundred fifty-six patients (38%) with premorbid ß-blocker exposure were identified. Overall ICU mortality rate was 15.1%. In adjusted models, premorbid ß-blocker exposure was associated with decreased ICU (adjusted odds ratio, 0.80; 95% CI, 0.66-0.97; p = 0.025) and hospital (adjusted odds ratio, 0.83; 95% CI, 0.71-0.99; p = 0.033) mortality. The risk reduction in ICU mortality of 16% was significant (hazard ratio, 0.84, 95% CI, 0.71-0.99; p = 0.037). In particular, exposure to noncardioselective ß-blocker before septic episode was associated with decreased mortality. Sequential Organ Failure Assessment score analysis showed that premorbid ß-blocker exposure had potential benefits in reducing respiratory and neurologic dysfunction. CONCLUSIONS: This study suggests that ß-blocker exposure prior to sepsis, especially to noncardioselective ß blockers, may be associated with better outcome. The findings suggest prospective evaluation of ß-blocker use in the management of sepsis.

Immunophenotyping of Peripheral Blood Mononuclear Cells in Septic Shock Patients With High-Dimensional Flow Cytometry Analysis Reveals Two Subgroups With Differential Responses to Immunostimulant Drugs.

Sepsis is associated with a dysregulated inflammatory response to infection. Despite the activation of inflammation, an immune suppression is often observed, predisposing patients to secondary infections. Therapies directed at restoration of immunity may be considered but should be guided by the immune status of the patients. In this paper, we described the use of a high-dimensional flow cytometry (HDCyto) panel to assess the immunophenotype of patients with sepsis. We then isolated peripheral blood mononuclear cells (PBMCs) from patients with septic shock and mimicked a secondary infection by stimulating PBMCs for 4 h in vitro with lipopolysaccharide (LPS) with or without prior exposure to either IFN-γ, or LAG-3Ig. We evaluated the response by means of flow cytometry and high-resolution clustering cum differential analysis and compared the results to PBMCs from healthy donors. We observed a heterogeneous immune response in septic patients and identified two major subgroups: one characterized by hypo-responsiveness (Hypo) and another one by hyper-responsiveness (Hyper). Hypo and Hyper groups showed significant differences in the production of cytokines/chemokine and surface human leukocyte antigen-DR (HLA-DR) expression in response to LPS stimulation, which were observed across all cell types. When pre-treated with either interferon gamma (IFN-γ) or lymphocyte-activation gene 3 (LAG)-3 recombinant fusion protein (LAG-3Ig) prior to LPS stimulation, cells from the Hypo group were shown to be more responsive to both immunostimulants than cells from the Hyper group. Our results demonstrate the importance of patient stratification based on their immune status prior to any immune therapies. Once sufficiently scaled, this approach may be useful for prescribing the right immune therapy for the right patient at the right time, the key to the success of any therapy.

Validation of a classification system for causes of death in critical care: an assessment of inter-rater reliability.

OBJECTIVE: Trials in critical care have previously used unvalidated systems to classify cause of death. We aimed to provide initial validation of a method to classify cause of death in intensive care unit patients. DESIGN, SETTING AND PARTICIPANTS: One hundred case scenarios of patients who died in an ICU were presented online to raters, who were asked to select a proximate and an underlying cause of death for each, using the ICU Deaths Classification and Reason (ICU-DECLARE) system. We evaluated two methods of categorising proximate cause of death (designated Lists A and B) and one method of categorising underlying cause of death. Raters were ICU specialists and research coordinators from Australia, New Zealand and the United Kingdom. MAIN OUTCOME MEASURES: Inter-rater reliability, as measured by the Fleiss multirater kappa, and the median proportion of raters choosing the most likely diagnosis (defined as the most popular classification choice in each case). RESULTS: Across all raters and cases, for proximate cause of death List A, kappa was 0.54 (95% CI, 0.49-0.60), and for proximate cause of death List B, kappa was 0.58 (95% CI, 0.53-0.63). For the underlying cause of death, kappa was 0.48 (95% CI, 0.44-0.53). The median proportion of raters choosing the most likely diagnosis for proximate cause of death, List A, was 77.5% (interquartile range [IQR], 60.0%-93.8%), and the median proportion choosing the most likely diagnosis for proximate cause of death, List B, was 82.5% (IQR, 60.0%-92.5%). The median proportion choosing the most likely diagnosis for underlying cause was 65.0% (IQR, 50.0%-81.3%). Kappa and median agreement were similar between countries. ICU specialists showed higher kappa and median agreement than research coordinators. CONCLUSIONS: The ICU-DECLARE system allowed ICU doctors to classify the proximate cause of death of patients who died in the ICU with substantial reliability.