Intensive care unit interventions to promote sleep and circadian biology in reducing incident delirium: a scoping review.

RATIONALE/OBJECTIVES: Despite plausible pathophysiological mechanisms, research is needed to confirm the relationship between sleep, circadian rhythm and delirium in patients admitted to the intensive care unit (ICU). The objective of this review is to summarise existing studies promoting, in whole or in part, the normalisation of sleep and circadian biology and their impact on the incidence, prevalence, duration and/or severity of delirium in ICU. METHODS: A sensitive search of electronic databases and conference proceedings was completed in March 2023. Inclusion criteria were English-language studies of any design that evaluated in-ICU non-pharmacological, pharmacological or mixed intervention strategies for promoting sleep or circadian biology and their association with delirium, as assessed at least daily. Data were extracted and independently verified. RESULTS: Of 7886 citations, we included 50 articles. Commonly evaluated interventions include care bundles (n=20), regulation or administration of light therapy (n=5), eye masks and/or earplugs (n=5), one nursing care-focused intervention and pharmacological intervention (eg, melatonin and ramelteon; n=19). The association between these interventions and incident delirium or severity of delirium was mixed. As multiple interventions were incorporated in included studies of care bundles and given that there was variable reporting of compliance with individual elements, identifying which components might have an impact on delirium is challenging. CONCLUSIONS: This scoping review summarises the existing literature as it relates to ICU sleep and circadian disruption (SCD) and delirium in ICU. Further studies are needed to better understand the role of ICU SCD promotion interventions in delirium mitigation.

The Predicted Outcome of Spinal Cord Stimulation in Patients With a Psychopathological Disorder and Persistent Spinal Pain Syndrome Type 2: A Systematic Review From 2009 to 2021.

OBJECTIVES: Psychologic screening is often included as a mandatory component of evaluation of the impact of psychopathology disorders on the predicted outcome of spinal cord stimulation (SCS) for patients with chronic pain due to persistent spinal pain syndrome type 2 (PSPS type 2). The conclusion of such screenings can influence the decision to offer SCS therapy to a patient. However, evidence on the impact of psychopathology on SCS outcomes is still scarce. MATERIALS AND METHODS: To address this knowledge gap, we systematically reviewed the literature from 2009 to 2021 to explore the correlation between the presence of a psychopathological disorder and the predicted outcome of SCS in patients with PSPS type 2. The literature search was conducted using various online data bases with "failed back surgery syndrome," "psychopathology," and "spinal cord stimulation" used as essential keywords. The identified studies were organized in a Rayyan AI data base, and the quality was analyzed with the Critical Appraisal Skills Program tool. RESULTS: Our search generated the identification of 468 original articles, of which two prospective and four retrospective studies met our inclusion criteria. These studies reported pain relief, a reduction of symptoms of anxiety and depression, and an improvement in rumination on the Pain Catastrophizing Scale in patients with PSPS type 2 after SCS therapy. The studies also found contradictory outcomes measured using the Oswestry Disability Index, and in terms of the impact of psychopathological disorder on the clinical outcome and revision rate of the SCS system. CONCLUSION: In this systematic review, we found no convincing evidence that the presence of a psychopathological disorder affects the predicted outcome of SCS therapy in patients with PSPS type 2.

Feasibility, safety, and patient acceptability of electronic inspiratory muscle training in patients who require prolonged mechanical ventilation in the intensive care unit: A dual-centre observational study.

BACKGROUND: Inspiratory muscle training (IMT) is an intervention that can be used to rehabilitate the respiratory muscle deconditioning experienced by patients with critical illness, requiring prolonged mechanical ventilation. Clinicians are currently using mechanical threshold IMT devices that have limited resistance ranges. OBJECTIVES: The objective of this study was to evaluate the safety, feasibility, and acceptability of using an electronic device to facilitate IMT with participants requiring prolonged mechanical ventilation. METHOD: A dual-centre observational cohort study, with convenience sampling, was conducted at two tertiary intensive care units. Daily training supervised by intensive care unit physiotherapists was completed with the electronic IMT device. A priori definitions for feasibility, safety, and acceptability were determined. Feasibility was defined as more than 80% of planned sessions completed. Safety was defined as no major adverse events and less than 3% minor adverse event rate, and acceptability was evaluated following the acceptability of intervention framework principles. RESULTS: Forty participants completed 197 electronic IMT treatment sessions. Electronic IMT was feasible, with 81% of planned sessions completed. There were 10% minor adverse events and no major adverse events. All the minor adverse events were transient without clinical consequences. All the participants who recalled completing electronic IMT sessions reported that the training was acceptable. Acceptability was demonstrated; over 85% of participants reported that electronic IMT was either helpful or beneficial and that electronic IMT assisted their recovery. CONCLUSION: Electronic IMT is feasible and acceptable to complete with critically ill participants who require prolonged mechanical ventilation. As all minor adverse events were transient without clinical consequences, electronic IMT can be considered a relatively safe intervention with patients who require prolonged mechanical ventilation.

Characteristics and Outcomes of Very Elderly Patients Admitted to Intensive Care: A Retrospective Multicenter Cohort Analysis.

OBJECTIVES: To characterize and compare trends in ICU admission, hospital outcomes, and resource utilization for critically ill very elderly patients (≥ 80 yr old) compared with the younger cohort (16-79 yr old). DESIGN: A retrospective multicenter cohort study. SETTING: One-hundred ninety-four ICUs contributing data to the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database between January 2006 and December 2018. PATIENTS: Adult (≥ 16 yr) patients admitted to Australian and New Zealand ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Very elderly patients with a mean ± sd age of 84.8 ± 3.7 years accounted for 14.8% (232,582/1,568,959) of all adult ICU admissions. They had higher comorbid disease burden and illness severity scores compared with the younger cohort. Hospital (15.4% vs 7.8%, p < 0.001) and ICU mortality (8.5% vs 5.2%, p < 0.001) were higher in the very elderly. They stayed fewer days in ICU, but longer in hospital and had more ICU readmissions. Among survivors, a lower proportion of very elderly was discharged home (65.2% vs 82.4%, p < 0.001), and a higher proportion was discharged to chronic care/nursing home facilities (20.1% vs 7.8%, p < 0.001). Although there was no change in the proportion of very elderly ICU admissions over the study period, they showed a greater decline in risk-adjusted mortality (6.3% [95% CI, 5.9%-6.7%] vs 4.0% [95% CI, 3.7%-4.2%] relative reduction per year, p < 0.001) compared with the younger cohort. The mortality of very elderly unplanned ICU admissions improved faster than the younger cohort ( p < 0.001), whereas improvements in mortality among elective surgical ICU admissions were similar in both groups ( p = 0.45). CONCLUSIONS: The proportion of ICU admissions greater than or equal to 80 years old did not change over the 13-year study period. Although their mortality was higher, they showed improved survivorship over time, especially in the unplanned ICU admission subgroup. A higher proportion of survivors were discharged to chronic care facilities.

Inhaled nebulised unfractionated heparin (UFH) for the treatment of hospitalised patients with COVID-19: A randomised controlled pilot study.

There is a strong scientific rationale to use nebulised unfractionated heparin (UFH) in treating patients with COVID-19. This pilot study investigated whether nebulised UFH was safe and had any impact on mortality, length of hospitalisation and clinical progression, in the treatment of hospitalised patients with COVID-19. This parallel group, open label, randomised trial included adult patients with confirmed SARS-CoV-2 infection admitted to two hospitals in Brazil. One hundred patients were planned to be randomised to either "standard of care" (SOC) or SOC plus nebulized UFH. The trial was stopped after randomisation of 75 patients due to falling COVID-19 hospitalisation rates. Significance tests were 1-sided test (10% significance level). The key analysis populations were intention to treat (ITT) and modified ITT (mITT) which excluded (from both arms) subjects admitted to ITU or who died within 24 h of randomisation. In the ITT population (n = 75), mortality was numerically lower for nebulised UFH (6 out of 38 patients; 15.8%) versus SOC (10 out of 37 patients; 27.0%), but not statistically significant; odds ratio (OR) 0.51, p = 0.24. However, in the mITT population, nebulised UFH reduced mortality (OR 0.2, p = 0.035). Length of hospital stay was similar between groups, but at day 29, there was a greater improvement in ordinal score following treatment with UFH in the ITT and mITT populations (p = 0.076 and p = 0.012 respectively), while mechanical ventilation rates were lower with UFH in the mITT population (OR 0.31; p = 0.08). Nebulised UFH did not cause any significant adverse events. In conclusion, nebulised UFH added to SOC in hospitalised patients with COVID-19 was well tolerated and showed clinical benefit, particularly in patients who received at least 6 doses of heparin. This trial was funded by The J.R. Moulton Charity Trust and registered under REBEC RBR-8r9hy8f (UTN code: U1111-1263-3136).

The accuracy of simple, feasible alternatives to polysomnography for assessing sleep in intensive care: An observational study.

BACKGROUND: Sleep disturbance is common in intensive care patients. Understanding the accuracy of simple, feasible sleep measurement techniques is essential to informing their possible role in usual clinical care. OBJECTIVE: The aim of the study was to investigate whether sleep monitoring techniques such as actigraphy (ACTG), behavioural assessments, and patient surveys are comparable with polysomnography (PSG) in accurately reporting sleep quantity and quality among conscious, intensive care patients. METHODS: An observational study was conducted in 20 patients admitted to the intensive care unit (ICU) for a minimum duration of 24 h, who underwent concurrent sleep monitoring via PSG, ACTG, nursing-based observations, and self-reported assessment using the Richards-Campbell Sleep Questionnaire. RESULTS: The reported total sleep time (TST) for the 20 participants measured by PSG was 328.2 min (±106 min) compared with ACTG (362.4 min [±62.1 min]; mean difference = 34.22 min [±129 min]). Bland-Altman analysis indicated that PSG and ACTG demonstrated clinical agreement and did not perform differently across a number of sleep variables including TST, awakening, sleep-onset latency, and sleep efficiency. Nursing observations overestimated sleep duration compared to PSG TST (mean difference = 9.95 ± 136.3 min, p > 0.05), and patient-reported TST was underestimated compared to PSG TST (mean difference = -51.81 ± 144.1 7, p > 0.05). CONCLUSIONS: Amongst conscious patients treated in the ICU, sleep characteristics measured by ACTG were similar to those measured by PSG. ACTG may provide a clinically feasible and acceptable proxy approach to sleep monitoring in conscious ICU patients.

Does mechanical threshold inspiratory muscle training promote recovery and improve outcomes in patients who are ventilator-dependent in the intensive care unit? The IMPROVE randomised trial.

BACKGROUND: In patients who are ventilator-dependent in the intensive care unit, inspiratory muscle training may improve inspiratory muscle strength and accelerate liberation from the ventilator, but optimal training parameters are yet to be established, and little is known about the impact of inspiratory muscle training on quality of life or dyspnoea. Thus, we sought to ascertain whether inspiratory muscle training, commenced while ventilator-dependent, would improve outcomes for patients invasively ventilated for 7 days or longer. METHODS: In this randomised trial with assessor blinding and intention-to-treat analysis, 70 participants (mechanically ventilated ≥7 days) were randomised to receive once-daily supervised high-intensity inspiratory muscle training with a mechanical threshold device in addition to usual care or to receive usual care (control). Primary outcomes were inspiratory muscle strength (maximum inspiratory pressure % predicted) and endurance (fatigue resistance index) at ventilator liberation and 1 week later. Secondary outcomes included quality of life (SF-36v2, EQ-5D), dyspnoea, physical function, duration of ventilation, and in-hospital mortality. RESULTS: Thirty-three participants were randomly allocated to the training group, and 37 to the control group. There were no statistically significant differences in strength (maximum inspiratory pressure) (95% confidence interval [CI]: -7.4 to 14.0) or endurance (fatigue resistance index) (95% CI: -0.003 to 0.436). Quality of life improved significantly more in the training group than in the control group (EQ-5D: 17.2; 95% CI: 1.3-33.0) (SF-36-PCS: 6.97; 95% CI: 1.96-12.00). Only the training group demonstrated significant reductions in dyspnoea (-1.5 at rest, -1.9 during exercise). There were no between-group differences in duration of ventilation or other measures. In-hospital mortality was higher in the control group than in the training group (9 vs 4, 24% vs 12%, p = 0.23). CONCLUSIONS: In patients who are ventilator-dependent, mechanical threshold loading inspiratory muscle training improves quality of life and dyspnoea, even in the absence of strength improvements or acceleration of ventilator liberation.

Can nebulised HepArin Reduce morTality and time to Extubation in patients with COVID-19 Requiring invasive ventilation Meta-Trial (CHARTER-MT): Protocol and statistical analysis plan for an investigator-initiated international meta-trial of prospective randomised clinical studies.

There is significant interest in the potential for nebulised unfractionated heparin (UFH), as a novel therapy for patients with COVID-19 induced acute hypoxaemic respiratory failure requiring invasive ventilation. The scientific and biological rationale for nebulised heparin stems from the evidence for extensive activation of coagulation resulting in pulmonary microvascular thrombosis in COVID-19 pneumonia. Nebulised delivery of heparin to the lung may limit alveolar fibrin deposition and thereby limit progression of lung injury. Importantly, laboratory studies show that heparin can directly inactivate the SARS-CoV-2 virus, thereby prevent its entry into and infection of mammalian cells. UFH has additional anti-inflammatory and mucolytic properties that may be useful in this context. METHODS AND INTERVENTION: The Can nebulised HepArin Reduce morTality and time to Extubation in Patients with COVID-19 Requiring invasive ventilation Meta-Trial (CHARTER-MT) is a collaborative prospective individual patient data analysis of on-going randomised controlled clinical trials across several countries in five continents, examining the effects of inhaled heparin in patients with COVID-19 requiring invasive ventilation on various endpoints. Each constituent study will randomise patients with COVID-19 induced respiratory failure requiring invasive ventilation. Patients are randomised to receive nebulised heparin or standard care (open label studies) or placebo (blinded placebo-controlled studies) while under invasive ventilation. Each participating study collect a pre-defined minimum dataset. The primary outcome for the meta-trial is the number of ventilator-free days up to day 28 day, defined as days alive and free from invasive ventilation.

Inhaled nebulised unfractionated heparin for the treatment of hospitalised patients with COVID-19: A multicentre case series of 98 patients.

AIMS: To determine the safety and efficacy-potential of inhaled nebulised unfractionated heparin (UFH) in the treatment of hospitalised patients with COVID-19. METHODS: Retrospective, uncontrolled multicentre single-arm case series of hospitalised patients with laboratory-confirmed COVID-19, treated with inhaled nebulised UFH (5000 IU q8h, 10 000 IU q4h, or 25 000 IU q6h) for 6 ± 3 (mean ± standard deviation) days. Outcomes were activated partial thromboplastin time (APTT) before treatment (baseline) and highest-level during treatment (peak), and adverse events including bleeding. Exploratory efficacy outcomes were oxygenation, assessed by ratio of oxygen saturation to fraction of inspired oxygen (FiO2 ) and FiO2 , and the World Health Organisation modified ordinal clinical scale. RESULTS: There were 98 patients included. In patients on stable prophylactic or therapeutic systemic anticoagulant therapy but not receiving therapeutic UFH infusion, APTT levels increased from baseline of 34 ± 10 seconds to a peak of 38 ± 11 seconds (P < .0001). In 3 patients on therapeutic UFH infusion, APTT levels did not significantly increase from baseline of 72 ± 20 to a peak of 84 ± 28 seconds (P = .17). Two patients had serious adverse events: bleeding gastric ulcer requiring transfusion and thigh haematoma; both were on therapeutic anticoagulation. Minor bleeding occurred in 16 patients, 13 of whom were on therapeutic anticoagulation. The oxygen saturation/FiO2 ratio and the FiO2 worsened before and improved after commencement of inhaled UFH (change in slope, P < .001). CONCLUSION: Inhaled nebulised UFH in hospitalised patients with COVID-19 was safe. Although statistically significant, inhaled nebulised UFH did not produce a clinically relevant increase in APTT (peak values in the normal range). Urgent randomised evaluation of nebulised UFH in patients with COVID-19 is warranted and several studies are currently underway.

Characteristics and outcomes of Aboriginal and Torres Strait Islander patients with dialysis-dependent kidney disease in Australian intensive care units.

BACKGROUND: In Australia, 531 people per million population have dialysis-dependent chronic kidney disease (CKD5D). The incidence is four times higher for Aboriginal and Torres Strait Islander (indigenous) people compared with non-Indigenous Australians. CKD5D increases the risk of hospitalisation, admission to the intensive care unit (ICU) and mortality compared with patients without CKD5D. There is limited literature describing short-term outcomes of patients with CKD5D who are admitted to the ICU, comparing indigenous and non-indigenous patients. AIMS: This registry-based retrospective cohort analysis compared demographic and clinical data between indigenous and non-indigenous patients with CKD5D and tested whether indigenous status predicted short-term outcomes independently of other contributing factors. Adjusted hospital mortality was the primary outcome measure. METHODS: Data were from the Australian and New Zealand Intensive Care Society's Centre for Outcome and Resource Evaluation Adult Patient Database. Australian ICU admissions between 2010 and 2017 were included. Data from 173 ICU (2136 beds) include 1 051 697 ICU admissions, of which 23 793 had a pre-existing diagnosis of CKD5D. RESULTS: Indigenous patients comprised 11.9% of CKD5D patients in ICU. CKD5D was prevalent among 4.9% of indigenous and 2.9% of non-indigenous ICU admissions. Indigenous patients were 13.5 years younger, had fewer comorbidities and lower crude mortality despite equivalent calculated mortality risk. After adjusting for age, remoteness and severity of illness, indigenous status did not predict mortality. CONCLUSIONS: Socioeconomic disadvantage contributes to earlier development of CKD5D and the overrepresentation in ICU of indigenous people. Mortality is equivalent once correcting for confounders, but addressing inequality requires strengthening preventative care.

Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study.

BACKGROUND: Current incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS). METHODS: An international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared. FINDINGS: 12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved. INTERPRETATION: More than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.

INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP): Protocol and statistical analysis plan for an investigator-initiated international metatrial of randomised studies.

AIMS: Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale that warrants urgent investigation of its therapeutic potential in patients with COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus' entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anticoagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis. METHODS: The INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP) metatrial is a prospective individual patient data analysis of on-going randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries. Participating studies randomise adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome for the metatrial is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have additional outcomes. ANALYSIS: We use a Bayesian approach to monitoring, followed by analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow-up or withdrawn. TRIAL REGISTRATION, ETHICS AND DISSEMINATION: The metatrial is registered at ClinicalTrials.gov ID NCT04635241. Each contributing study is individually registered and has received approval of the relevant ethics committee or institutional review board. Results of this study will be shared with the World Health Organisation, published in scientific journals and presented at scientific meetings.

Addressing ethical confusion in deceased donation and transplantation research: the need for dedicated guidance.

Innovative research in deceased donation and transplantation often presents ethical challenges for researchers and those responsible for ethical governance of research. These challenges have been recognized as potential barriers to the conduct of research. We review the literature to identify and describe ethical considerations that may cause confusion or uncertainty in the context of research involving potential deceased donors or deceased donor transplantation. We normatively examine these considerations and discuss their implications for the ethical conduct of research. In addition to the complexities of research involving critically ill, dying or recently deceased individuals, uncertainty may arise regarding the ethical status of various individuals who may be involved in research aimed at improving availability and outcomes of organ transplantation. Consequently, routine ethical guidelines for clinical research may fail to provide clear guidance with regards to the design, conduct and governance of some deceased donation or transplantation studies. Ethical uncertainty may result in delays or barriers to research, or neglect of important ethical considerations. Specific ethical guidance is needed to support research in deceased donation and transplantation as the ethical considerations that arise in the design and conduct of such research may not be addressed in the existing guidelines for human research.

Compliance Phenotypes in Early Acute Respiratory Distress Syndrome before the COVID-19 Pandemic.

Rationale: A novel model of phenotypes based on set thresholds of respiratory system compliance (Crs) was recently postulated in context of coronavirus disease (COVID-19) acute respiratory distress syndrome (ARDS). In particular, the dissociation between the degree of hypoxemia and Crs was characterized as a distinct ARDS phenotype.Objectives: To determine whether such Crs-based phenotypes existed among patients with ARDS before the COVID-19 pandemic and to closely examine the Crs-mortality relationship.Methods: We undertook a secondary analysis of patients with ARDS, who were invasively ventilated on controlled modes and enrolled in a large, multinational, epidemiological study. We assessed Crs, degree of hypoxemia, and associated Crs-based phenotypic patterns with their characteristics and outcomes.Measurements and Main Results: Among 1,117 patients with ARDS who met inclusion criteria, the median Crs was 30 (interquartile range, 23-40) ml/cm H2O. One hundred thirty-six (12%) patients had preserved Crs (≥50 ml/cm H2O; phenotype with low elastance ["phenotype L"]), and 827 (74%) patients had poor Crs (<40 ml/cm H2O; phenotype with high elastance ["phenotype H"]). Compared with those with phenotype L, patients with phenotype H were sicker and had more comorbidities and higher hospital mortality (32% vs. 45%; P < 0.05). A near complete dissociation between PaO2/FiO2 and Crs was observed. Of 136 patients with phenotype L, 58 (43%) had a PaO2/FiO2 < 150. In a multivariable-adjusted analysis, the Crs was independently associated with hospital mortality (adjusted odds ratio per ml/cm H2O increase, 0.988; 95% confidence interval, 0.979-0.996; P = 0.005).Conclusions: A wide range of Crs was observed in non-COVID-19 ARDS. Approximately one in eight patients had preserved Crs. PaO2/FiO2 and Crs were dissociated. Lower Crs was independently associated with higher mortality. The Crs-mortality relationship lacked a clear transition threshold.

Relative Hypotension and Adverse Kidney-related Outcomes among Critically Ill Patients with Shock. A Multicenter, Prospective Cohort Study.

Rationale: There are no prospective observational studies exploring the relationship between relative hypotension and adverse kidney-related outcomes among critically ill patients with shock.Objectives: To investigate the magnitude of relative hypotension during vasopressor support among critically ill patients with shock and to determine whether such relative hypotension is associated with new significant acute kidney injury (AKI) or major adverse kidney events (MAKE) within 14 days of vasopressor initiation.Methods: At seven multidisciplinary ICUs, 302 patients, aged ≥40 years and requiring ≥4 hours of vasopressor support for nonhemorrhagic shock, were prospectively enrolled. We assessed the time-weighted average of the mean perfusion pressure (MPP) deficit (i.e., the percentage difference between patients' preillness basal MPP and achieved MPP) during vasopressor support and the percentage of time points with an MPP deficit > 20% as key exposure variables. New significant AKI was defined as an AKI-stage increase of two or more (Kidney Disease: Improving Global Outcome creatinine-based criteria).Measurements and Main Results: The median MPP deficit was 19% (interquartile range, 13-25), and 54% (interquartile range, 19-82) of time points were spent with an MPP deficit > 20%. Seventy-three (24%) patients developed new significant AKI; 86 (29%) patients developed MAKE. For every percentage increase in the time-weighted average MPP deficit, multivariable-adjusted odds of developing new significant AKI and MAKE increased by 5.6% (95% confidence interval, 2.2-9.1; P = 0.001) and 5.9% (95% confidence interval, 2.2-9.8; P = 0.002), respectively. Likewise, for every one-unit increase in the percentage of time points with an MPP deficit > 20%, multivariable-adjusted odds of developing new significant AKI and MAKE increased by 1.2% (0.3-2.2; P = 0.008) and 1.4% (0.4-2.4; P = 0.004), respectively.Conclusions: Vasopressor-treated patients with shock are often exposed to a significant degree and duration of relative hypotension, which is associated with new-onset, adverse kidney-related outcomes.Study registered with Australian New Zealand Clinical Trial Registry (ACTRN 12613001368729).

Outcomes Six Months after Delivering 100% or 70% of Enteral Calorie Requirements during Critical Illness (TARGET). A Randomized Controlled Trial.

Rationale: The long-term effects of delivering approximately 100% of recommended calorie intake via the enteral route during critical illness compared with a lesser amount of calories are unknown.Objectives: Our hypotheses were that achieving approximately 100% of recommended calorie intake during critical illness would increase quality-of-life scores, return to work, and key life activities and reduce death and disability 6 months later.Methods: We conducted a multicenter, blinded, parallel group, randomized clinical trial, with 3,957 mechanically ventilated critically ill adults allocated to energy-dense (1.5 kcal/ml) or routine (1.0 kcal/ml) enteral nutrition.Measurements and Main Results: Participants assigned energy-dense nutrition received more calories (percent recommended energy intake, mean [SD]; energy-dense: 103% [28] vs. usual: 69% [18]). Mortality at Day 180 was similar (560/1,895 [29.6%] vs. 539/1,920 [28.1%]; relative risk 1.05 [95% confidence interval, 0.95-1.16]). At a median (interquartile range) of 185 (182-193) days after randomization, 2,492 survivors were surveyed and reported similar quality of life (EuroQol five dimensions five-level quality-of-life questionnaire visual analog scale, median [interquartile range]: 75 [60-85]; group difference: 0 [95% confidence interval, 0-0]). Similar numbers of participants returned to work with no difference in hours worked or effectiveness at work (n = 818). There was no observed difference in disability (n = 1,208) or participation in key life activities (n = 705).Conclusions: The delivery of approximately 100% compared with 70% of recommended calorie intake during critical illness does not improve quality of life or functional outcomes or increase the number of survivors 6 months later.

Annual prevalence, characteristics, and outcomes of intensive care patients with skin or soft tissue infections in Australia and New Zealand: A retrospective cohort study between 2006-2017.

BACKGROUND: There are limited published data on the epidemiology of skin and soft tissue infections (SSTIs) requiring intensive care unit (ICU) admission. This study intended to describe the annual prevalence, characteristics, and outcomes of critically ill adult patients admitted to the ICU for an SSTI. METHODS: This was a registry-based retrospective cohort study, using data submitted to the Australian and New Zealand Intensive Care Society Adult Patient Database for all admissions with SSTI between 2006 and 2017. The inclusion criteria were as follows: primary diagnosis of SSTI and age ≥16 years. The exclusion criteria were as follows: ICU readmissions (during the same hospital admission) and transfers from ICUs from other hospitals. The primary outcome was in-hospital mortality, and the secondary outcomes were ICU mortality and length of stay (LOS) in the ICU and hospital with independent predictors of outcomes. RESULTS: Admissions due to SSTI accounted for 10 962 (0.7%) of 1 470 197 ICU admissions between 2006 and 2017. Comorbidities were present in 25.2% of the study sample. The in-hospital mortality was 9% (991/10 962), and SSTI necessitating ICU admission accounted for 0.07% of in-hospital mortality of all ICU admissions between 2006 and 2017. Annual prevalence of ICU admissions for SSTI increased from 0.4% to 0.9% during the study period, but in-hospital mortality decreased from 16.1% to 6.8%. The median ICU LOS was 2.1 days (interquartile range = 3.4), and the median hospital LOS was 12.1 days (interquartile range = 20.6). ICU LOS remained stable between 2006 and 2017 (2.0-2.1 days), whereas hospital LOS decreased from 15.7 to 11.2 days. Predictors for in-hospital mortality included Australian and New Zealand Risk of Death scores [odds ratio (OR): 1.07; confidence interval (CI) (1.05, 1.09); p < 0.001], any comorbidity except diabetes [OR: 2.00; CI (1.05, 3.79); p = 0.035], and admission through an emergency response call [OR: 2.07; CI (1.03, 4.16); p = 0.041]. CONCLUSIONS: SSTIs are uncommon as primary ICU admission diagnosis. Although the annual prevalence of ICU admissions for SSTI has increased, in-hospital mortality and hospital LOS have decreased over the last decade.

Qualitative Evaluation of the Influence of Acute Oxaliplatin-Induced Peripheral Neuropathy on Quality of Life and Activities of Daily Life.

INTRODUCTION/AIMS: Oxaliplatin often causes acute or chronic peripheral neuropathy in patients with an intestinal or pancreatic tumor, but in-depth insights in its influence on quality of life (QoL) are lacking. We explored the influence of acute oxaliplatin-induced peripheral neuropathy (OIPN) on daily QoL in these patients. METHODS: We performed semistructured interviews with a purposive sample of patients receiving oxaliplatin and possibly experiencing acute OIPN. Interviews were audio-recorded, transcribed verbatim, and coded by two researchers. Data were analyzed by using the constant comparative method for content analysis with ATLAS.ti software. RESULTS: After nine patients, saturation took place. In total, 11 patients were interviewed. Four themes were extracted from the data: (1) adverse effects, (2) physical (un)well-being, (3) emotional aspects, and (4) treatment aspects. All participants were suffering from acute OIPN to a certain extent, leading to restrictions in daily activities such as household chores, but also to a decrease in mobility and independency. Other adverse effects such as general malaise and gastrointestinal side effects also influenced the participants' well-being, as did the diagnosis and prognosis of their disease. CONCLUSION: Acute OIPN, together with other side effects of chemotherapeutic treatment and the difficulties that come with the diagnosis of cancer and its prognosis, largely influences patients' daily QoL. Managing expectations (by patient education) seems important.

Respiratory Muscle Rehabilitation in Patients with Prolonged Mechanical Ventilation: A Targeted Approach.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: insights from the LUNG SAFE study.

BACKGROUND: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. METHODS: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). RESULTS: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). CONCLUSIONS: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. TRIAL REGISTRATION: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073.