Early Active Mobilization during Mechanical Ventilation in the ICU.

BACKGROUND: Intensive care unit (ICU)-acquired weakness often develops in patients who are undergoing invasive mechanical ventilation. Early active mobilization may mitigate ICU-acquired weakness, increase survival, and reduce disability. METHODS: We randomly assigned 750 adult patients in the ICU who were undergoing invasive mechanical ventilation to receive increased early mobilization (sedation minimization and daily physiotherapy) or usual care (the level of mobilization that was normally provided in each ICU). The primary outcome was the number of days that the patients were alive and out of the hospital at 180 days after randomization. RESULTS: The median number of days that patients were alive and out of the hospital was 143 (interquartile range, 21 to 161) in the early-mobilization group and 145 days (interquartile range, 51 to 164) in the usual-care group (absolute difference, -2.0 days; 95% confidence interval [CI], -10 to 6; P = 0.62). The mean (±SD) daily duration of active mobilization was 20.8±14.6 minutes and 8.8±9.0 minutes in the two groups, respectively (difference, 12.0 minutes per day; 95% CI, 10.4 to 13.6). A total of 77% of the patients in both groups were able to stand by a median interval of 3 days and 5 days, respectively (difference, -2 days; 95% CI, -3.4 to -0.6). By day 180, death had occurred in 22.5% of the patients in the early-mobilization group and in 19.5% of those in the usual-care group (odds ratio, 1.15; 95% CI, 0.81 to 1.65). Among survivors, quality of life, activities of daily living, disability, cognitive function, and psychological function were similar in the two groups. Serious adverse events were reported in 7 patients in the early-mobilization group and in 1 patient in the usual-care group. Adverse events that were potentially due to mobilization (arrhythmias, altered blood pressure, and desaturation) were reported in 34 of 371 patients (9.2%) in the early-mobilization group and in 15 of 370 patients (4.1%) in the usual-care group (P = 0.005). CONCLUSIONS: Among adults undergoing mechanical ventilation in the ICU, an increase in early active mobilization did not result in a significantly greater number of days that patients were alive and out of the hospital than did the usual level of mobilization in the ICU. The intervention was associated with increased adverse events. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; TEAM ClinicalTrials.gov number, NCT03133377.).

Impact of High-Dose Early Mobilization on Outcomes for Patients with Diabetes: A Secondary Analysis of the TEAM Trial.

Rationale: Patients with diabetes represent almost 20% of all ICU admissions and might respond differently to high-dose early active mobilization. Objectives: To assess whether diabetes modified the relationship between the dose of early mobilization on clinical outcomes in the TEAM trial. Methods: All TEAM trial patients were included. The primary outcome was days alive and out of the hospital at Day 180. Secondary outcomes included 180-day mortality and long-term functional outcomes at Day 180. Logistic and median regression models were used to explore the effect of high-dose early mobilization on outcomes by diabetes status. Measurements and Main Results: All 741 patients from the original trial were included. Of these, 159 patients (21.4%) had diabetes. Patients with diabetes had fewer days alive and out of the hospital at Day 180 (124 [0-153] vs. 147 [82-164]; P = 0.013) and higher 180-day mortality (30% vs. 18%; P = 0.044). In patients receiving high-dose early mobilization, the number of days alive and out of the hospital at Day 180 was 73.0 (0.0-144.5) in patients with diabetes and 146.5 (95.8-163.0) in patients without diabetes (P value for interaction = 0.108). However, in patients with diabetes, high-dose early mobilization increased the odds of mortality at 180 days (adjusted odds ratio, 3.47; 95% confidence interval, 1.67-7.61; P value for interaction = 0.001). Conclusions: In this secondary analysis of the TEAM trial, in patients with diabetes, a high-dose early mobilization strategy did not significantly decrease the number of days alive and out of the hospital at Day 180, but it increased 180-day mortality.

High PEEP with recruitment maneuvers versus Low PEEP During General Anesthesia for Surgery - a Bayesian individual patient data meta-analysis of three randomized clinical trials.

BACKGROUND: The influence of high positive end-expiratory pressure (PEEP) with recruitment maneuvers on the occurrence of postoperative pulmonary complications after surgery is still not definitively established. Bayesian analysis can help to gain further insights from the available data and provide a probabilistic framework that is easier to interpret. Our objective was to estimate the posterior probability that the use of high PEEP with recruitment maneuvers is associated with reduced postoperative pulmonary complications in patients with intermediate-to-high risk under neutral, pessimistic, and optimistic expectations regarding the treatment effect. METHODS: Multilevel Bayesian logistic regression analysis on individual patient data from three randomized clinical trials carried out on surgical patients at Intermediate-to-High Risk for postoperative pulmonary complications. The main outcome was the occurrence of postoperative pulmonary complications in the early postoperative period. We studied the effect of high PEEP with recruitment maneuvers versus Low PEEP Ventilation. Priors were chosen to reflect neutral, pessimistic, and optimistic expectations of the treatment effect. RESULTS: Using a neutral, pessimistic, or optimistic prior, the posterior mean odds ratio (OR) for High PEEP with recruitment maneuvers compared to Low PEEP was 0.85 (95% Credible Interval [CrI] 0.71 to 1.02), 0.87 (0.72 to 1.04), and 0.86 (0.71 to 1.02), respectively. Regardless of prior beliefs, the posterior probability of experiencing a beneficial effect exceeded 90%. Subgroup analysis indicated a more pronounced effect in patients who underwent laparoscopy (OR: 0.67 [0.50 to 0.87]) and those at high risk for PPCs (OR: 0.80 [0.53 to 1.13]). Sensitivity analysis, considering severe postoperative pulmonary complications only or applying a different heterogeneity prior, yielded consistent results. CONCLUSION: High PEEP with recruitment maneuvers demonstrated a moderate reduction in the probability of PPC occurrence, with a high posterior probability of benefit observed consistently across various prior beliefs, particularly among patients who underwent laparoscopy.

Assessment of fluid responsiveness using pulse pressure variation, stroke volume variation, plethysmographic variability index, central venous pressure, and inferior vena cava variation in patients undergoing mechanical ventilation: a systematic review and meta-analysis.

IMPORTANCE: Maneuvers assessing fluid responsiveness before an intravascular volume expansion may limit useless fluid administration, which in turn may improve outcomes. OBJECTIVE: To describe maneuvers for assessing fluid responsiveness in mechanically ventilated patients. REGISTRATION: The protocol was registered at PROSPERO: CRD42019146781. INFORMATION SOURCES AND SEARCH: PubMed, EMBASE, CINAHL, SCOPUS, and Web of Science were search from inception to 08/08/2023. STUDY SELECTION AND DATA COLLECTION: Prospective and intervention studies were selected. STATISTICAL ANALYSIS: Data for each maneuver were reported individually and data from the five most employed maneuvers were aggregated. A traditional and a Bayesian meta-analysis approach were performed. RESULTS: A total of 69 studies, encompassing 3185 fluid challenges and 2711 patients were analyzed. The prevalence of fluid responsiveness was 49.9%. Pulse pressure variation (PPV) was studied in 40 studies, mean threshold with 95% confidence intervals (95% CI) = 11.5 (10.5-12.4)%, and area under the receiver operating characteristics curve (AUC) with 95% CI was 0.87 (0.84-0.90). Stroke volume variation (SVV) was studied in 24 studies, mean threshold with 95% CI = 12.1 (10.9-13.3)%, and AUC with 95% CI was 0.87 (0.84-0.91). The plethysmographic variability index (PVI) was studied in 17 studies, mean threshold = 13.8 (12.3-15.3)%, and AUC was 0.88 (0.82-0.94). Central venous pressure (CVP) was studied in 12 studies, mean threshold with 95% CI = 9.0 (7.7-10.1) mmHg, and AUC with 95% CI was 0.77 (0.69-0.87). Inferior vena cava variation (∆IVC) was studied in 8 studies, mean threshold = 15.4 (13.3-17.6)%, and AUC with 95% CI was 0.83 (0.78-0.89). CONCLUSIONS: Fluid responsiveness can be reliably assessed in adult patients under mechanical ventilation. Among the five maneuvers compared in predicting fluid responsiveness, PPV, SVV, and PVI were superior to CVP and ∆IVC. However, there is no data supporting any of the above mentioned as being the best maneuver. Additionally, other well-established tests, such as the passive leg raising test, end-expiratory occlusion test, and tidal volume challenge, are also reliable.

Association of Age, Frailty, and Strategy for Initiation of Renal-Replacement Therapy: A Post Hoc analysis of the STARRT-Acute Kidney Injury Trial.

INTRODUCTION: This study was designed to assess the association of age and frailty with clinical outcomes in patients with severe acute kidney injury (AKI), according to accelerated and standard renal-replacement therapy (RRT) initiation strategies in the STARRT-AKI trial. METHODS: This was a secondary analysis of an international randomized trial. Older age was defined as ≥65 years. Frailty was assessed using the clinical frailty scale (CFS) score and defined as a score ≥5. The primary outcome was all-cause mortality at 90 days. Secondary outcomes included RRT dependence and RRT-free days at 90 days. We used logistic and linear regression and interaction testing to explore the impact of age and frailty on clinical outcomes. RESULTS: Of 2,927 patients randomized in the STARRT-AKI trial, 1,616 (55.2%) were aged ≥65 years (median [interquartile range] 73.9 [69.4-78.9]). Older patients had greater comorbid cardiovascular and chronic kidney disease, were more likely to be surgical admissions and to receive vasopressors at baseline. Older patients had higher 90-day mortality (50.4% vs. 35.6%, adjusted-odds ratio (OR), 1.81 [1.53-2.13], p < 0.001). There was no significant difference in RRT dependence at 90 days between older and younger patients (8.7% vs. 7.8%, adjusted-OR, 1.21 [0.82-1.79], p = 0.325). Patients with frailty had higher mortality; but no difference in RRT dependence at 90 days. There was no significant interaction between age and CFS score in relation to mortality, RRT dependence at 90 days, and other secondary outcomes. There was no significant difference in the proportion of patients who received RRT in the standard-strategy stratified by age groups (adjusted-OR, 0.85 [0.67-1.08], p = 0.180). CONCLUSION: In this secondary analysis of the STARRT-AKI trial, older and frail patients had higher mortality at 90 days; however, there was no difference in RRT dependence. Mortality and RRT dependence were not modified by RRT initiation strategy in older or frail patients.

Dexmedetomidine and Propofol Sedation in Critically Ill Patients and Dose-associated 90-Day Mortality: A Secondary Cohort Analysis of a Randomized Controlled Trial (SPICE III).

Rationale: The SPICE III (Sedation Practice in Intensive Care Evaluation) trial reported significant heterogeneity in mortality with dexmedetomidine treatment. Supplemental propofol was commonly used to achieve desirable sedation. Objectives: To quantify the association of different infusion rates of dexmedetomidine and propofol, given in combination, with mortality and to determine if this is modified by age. Methods: We included 1,177 patients randomized in SPICE III to receive dexmedetomidine and given supplemental propofol, stratified by age (>65 or ⩽65 yr). We used double stratification analysis to produce quartiles of steady infusion rates of dexmedetomidine while escalating propofol dose and vice versa. We used Cox proportional hazard and multivariable regression adjusted for relevant clinical variable to evaluate the association of sedative dose with 90-day mortality. Measurements and Main Results: Younger patients (598 of 1,177 [50.8%]) received significantly higher doses of both sedatives compared with older patients to achieve comparable sedation depth. On double stratification analysis, escalating infusion rates of propofol to 1.27 mg/kg/h at a steady dexmedetomidine infusion rate (0.54 µg/kg/h) was associated with reduced adjusted mortality in younger but not older patients. This was consistent with multivariable regression modeling (hazard ratio, 0.59; 95% confidence interval, 0.43-0.78; P < 0.0001) adjusted for baseline risk and interaction with dexmedetomidine dose. In contrast, among younger patients, using multivariable regression, escalating dexmedetomidine infusion rate was associated with increased adjusted mortality (hazard ratio, 1.30; 95% confidence interval, 1.03-1.65; P = 0.029). Conclusions: In patients ⩽65 years of age sedated with dexmedetomidine and propofol combination, preferentially increasing the dose of propofol was associated with decreased adjusted 90-day mortality. Conversely, increasing dexmedetomidine may be associated with increased mortality. Clinical trial registered with www.clinicaltrials.gov (NCT01728558).

Conservative versus Liberal Oxygenation Targets in Intensive Care Unit Patients (ICONIC): A Randomized Clinical Trial.

Rationale: Supplemental oxygen is widely administered to ICU patients, but appropriate oxygenation targets remain unclear. Objectives: This study aimed to determine whether a low-oxygenation strategy would lower 28-day mortality compared with a high-oxygenation strategy. Methods: This randomized multicenter trial included mechanically ventilated ICU patients with an expected ventilation duration of at least 24 hours. Patients were randomized 1:1 to a low-oxygenation (PaO2, 55-80 mm Hg; or oxygen saturation as measured by pulse oximetry, 91-94%) or high-oxygenation (PaO2, 110-150 mm Hg; or oxygen saturation as measured by pulse oximetry, 96-100%) target until ICU discharge or 28 days after randomization, whichever came first. The primary outcome was 28-day mortality. The study was stopped prematurely because of the COVID-19 pandemic when 664 of the planned 1,512 patients were included. Measurements and Main Results: Between November 2018 and November 2021, a total of 664 patients were included in the trial: 335 in the low-oxygenation group and 329 in the high-oxygenation group. The median achieved PaO2 was 75 mm Hg (interquartile range, 70-84) and 115 mm Hg (interquartile range, 100-129) in the low- and high-oxygenation groups, respectively. At Day 28, 129 (38.5%) and 114 (34.7%) patients had died in the low- and high-oxygenation groups, respectively (risk ratio, 1.11; 95% confidence interval, 0.9-1.4; P = 0.30). At least one serious adverse event was reported in 12 (3.6%) and 17 (5.2%) patients in the low- and high-oxygenation groups, respectively. Conclusions: Among mechanically ventilated ICU patients with an expected mechanical ventilation duration of at least 24 hours, using a low-oxygenation strategy did not result in a reduction of 28-day mortality compared with a high-oxygenation strategy. Clinical trial registered with the National Trial Register and the International Clinical Trials Registry Platform (NTR7376).

Sepsis-associated acute kidney injury in patients with chronic kidney disease: Patient characteristics, prevalence, timing, trajectory, treatment and associated outcomes.

AIM: The features and outcomes of sepsis-associated acute kidney injury (SA-AKI) may be affected by chronic kidney disease (CKD). Accordingly, we aimed to compare SA-AKI in patients with or without CKD. METHODS: Retrospective cohort study in 12 intensive care units (ICU). We studied the prevalence, patient characteristics, timing, trajectory, treatment and outcomes of SA-AKI with and without CKD. RESULTS: Of 84 240 admissions, 7255 (8.6%) involved patients with CKD. SA-AKI was more common in patients with CKD (21% vs 14%; p < .001). CKD patients were older (70 vs. 60 years; p < .001), had a higher median Charlson co-morbidity index (5 vs. 3; p < .001) and acute physiology and chronic health evaluation (APACHE) III score (78 vs. 60; p < .001) and were more likely to receive renal replacement therapy (RRT) (25% vs. 17%; p < .001). They had less complete return to baseline function at ICU discharge (48% vs. 60%; p < .001), higher major adverse kidney events at day 30 (MAKE-30) (38% vs. 27%; p < .001), and higher hospital and 90-day mortality (21% vs. 13%; p < .001, and 27% vs. 16%; p < .001, respectively). After adjustment for patient characteristics and severity of illness, however, CKD was not an independent risk factor for increased 90-day mortality (OR 0.88; 95% CI 0.76-1.02; p = .08) or MAKE-30 (OR 0.98; 95% CI 0.80-1.09; p = .4). CONCLUSION: SA-AKI is more common in patients with CKD. Such patients are older, more co-morbid, have higher disease severity, receive different ICU therapies and have different trajectories of renal recovery and greater unadjusted mortality. However, after adjustment day-90 mortality and MAKE-30 risk were not increased by CKD.

Effect of Tele-ICU on Clinical Outcomes of Critically Ill Patients: The TELESCOPE Randomized Clinical Trial.

Importance: Despite its implementation in several countries, there has not been a randomized clinical trial to assess whether telemedicine in intensive care units (ICUs) could improve clinical outcomes of critically ill patients. Objective: To determine whether an intervention comprising daily multidisciplinary rounds and monthly audit and feedback meetings performed by a remote board-certified intensivist reduces ICU length of stay (LOS) compared with usual care. Design, Setting, and Participants: A parallel cluster randomized clinical trial with a baseline period in 30 general ICUs in Brazil in which daily multidisciplinary rounds performed by board-certified intensivists were not routinely available. All consecutive adult patients (aged ≥18 years) admitted to the participating ICUs, excluding those admitted due to justice-related issues, were enrolled between June 1, 2019, and April 7, 2021, with last follow-up on July 6, 2021. Intervention: Remote daily multidisciplinary rounds led by a board-certified intensivist through telemedicine, monthly audit and feedback meetings for discussion of ICU performance indicators, and provision of evidence-based clinical protocols. Main Outcomes and Measures: The primary outcome was ICU LOS at the patient level. Secondary outcomes included ICU efficiency, in-hospital mortality, incidence of central line-associated bloodstream infections, ventilator-associated events, catheter-associated urinary tract infections, ventilator-free days at 28 days, patient-days receiving oral or enteral feeding, patient-days under light sedation, and rate of patients with oxygen saturation values under that of normoxemia, assessed using generalized linear mixed models. Results: Among 17 024 patients (1794 in the baseline period and 15 230 in the intervention period), the mean (SD) age was 61 (18) years, 44.7% were female, the median (IQR) Sequential Organ Failure Assessment score was 6 (2-9), and 45.5% were invasively mechanically ventilated at admission. The median (IQR) time under intervention was 20 (16-21) months. Mean (SD) ICU LOS, adjusted for baseline assessment, did not differ significantly between the tele-critical care and usual care groups (8.1 [10.0] and 7.1 [9.0] days; percentage change, 8.2% [95% CI, -5.4% to 23.8%]; P = .24). Results were similar in sensitivity analyses and prespecified subgroups. There were no statistically significant differences in any other secondary or exploratory outcomes. Conclusions and Relevance: Daily multidisciplinary rounds conducted by a board-certified intensivist through telemedicine did not reduce ICU LOS in critically ill adult patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03920501.

Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction: The DEFENDER Randomized Clinical Trial.

Importance: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown. Objective: To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023. Intervention: Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models. Results: Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group. Conclusion and Relevance: The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin. Trial Registration: ClinicalTrials.gov Identifier: NCT05558098.

Intubation of critically ill patients: A pilot study of minute-by-minute physiological changes within an Australian tertiary intensive care unit.

BACKGROUND: There are no published minute-by-minute physiological assessment data for endotracheal intubation (ETT) performed in the intensive care unit (ICU). The majority of physiological data is available from Europe and North America where etomidate is the induction agent administered most commonly. AIMS: The aim of this study was to describe the feasibility of obtaining minute-by-minute physiological and medication data surrounding ETT in an Australian tertiary ICU and to assess its associated outcomes. METHODS: We performed a single-centre feasibility observational study. We obtained minute-by-minute data on physiological variables and medications for 15 min before and 30 min after ETT. We assessed feasibility as enrolled to screened patient ratio and completeness of data collection in enrolled patients. Severe hypotension (systolic blood pressure < 65 mmHg) and severe hypoxaemia (pulse oximetry saturation < 80%) were the secondary clinical outcomes. RESULTS: We screened 43 patients and studied 30 patients. The median age was 58.5 (interquartile range: 49-70) years, and 18 (60%) were male. Near-complete (97%) physiological and medication data were obtained in all patients at all times. Overall, 15 (50%) ETTs occurred after hours (17:30-08:00) and 90% were by video laryngoscopy with a 90% first-pass success rate. Prophylactic vasopressors were used in 50% of ETTs. Fentanyl was used in all except one ETT at a median dose of 2.5 mcg/kg. Propofol (63%) or midazolam (50%) were used as adjuncts at low dose. Rocuronium was used in all but one patient. There were no episodes of severe hypotension and only one episode of short-lived severe hypoxaemia. CONCLUSION: Minute-by-minute recording of ETT-associated physiological changes in the ICU was feasible but only fully available in two-thirds of the screened patients. ETT was based on fentanyl induction, low-dose adjunctive sedation, and frequent prophylactic vasopressor therapy and was associated with no severe hypotension and a single short-lived episode of severe hypoxaemia.

Frequency of and associations with alterations of medical emergency team calling criteria in a teaching hospital emergency department.

BACKGROUND: Medical emergency team (METs), activated by vital sign-based calling criteria respond to deteriorating patients in the hospital setting. Calling criteria may be altered where clinicians feel this is appropriate. Altered calling criteria (ACC) has not previously been evaluated in the emergency department (ED) setting. OBJECTIVES: The objectives of this study were to (i) describe the frequency of ACC in a teaching hospital ED and the number and type of vital signs that were modified and (ii) associations between ACC in the ED and differences in the baseline patient characteristics and adverse outcomes including subsequent MET activations, unplanned intensive care unit (ICU) admissions and death within 72 h of admission. METHODS: Retrospective observational study of patients presenting to an academic, tertiary hospital ED in Melbourne, Australia between January 1st, 2019 and December 31st, 2019. The primary outcome was frequency and nature of ACC in the ED. Secondary outcomes included differences in baseline patient characteristics, frequency of MET activation, unplanned ICU admission, and mortality in the first 72 h of admission between those with and without ACC in the ED. RESULTS: Amongst 14 159 ED admissions, 725 (5.1%) had ACC, most frequently for increased heart or respiratory rate. ACC was associated with older age and increased comorbidity. Such patients had a higher adjusted risk of MET activation (odds ratio [OR]: 3.14, 95% confidence interval [CI]: 2.50-3.91, p = <0.001), unplanned ICU admission (OR: 1.97, 95% CI: 1.17-3.14, p = 0.016), and death (OR: 3.87, 95% CI: 2.08-6.70, p = 0.020) within 72 h. CONCLUSIONS: ACC occurs commonly in the ED, most frequently for elevated heart and respiratory rates and is associated with worse patient outcomes. In some cases, ACC requires consultant involvement, more frequent vital sign monitoring, expeditious inpatient team review, or ICU referral.

Nutrition delivery across hospitalisation in critically ill patients with COVID-19: An observational study of the Australian experience.

BACKGROUND: Data on nutrition delivery over the whole hospital admission in critically ill patients with COVID-19 are scarce, particularly in the Australian setting. OBJECTIVES: The objective of this study was to describe nutrition delivery in critically ill patients admitted to Australian intensive care units (ICUs) with coronavirus disease 2019 (COVID-19), with a focus on post-ICU nutrition practices. METHODS: A multicentre observational study conducted at nine sites included adult patients with a positive COVID-19 diagnosis admitted to the ICU for >24 h and discharged to an acute ward over a 12-month recruitment period from 1 March 2020. Data were extracted on baseline characteristics and clinical outcomes. Nutrition practice data from the ICU and weekly in the post-ICU ward (up to week four) included route of feeding, presence of nutrition-impacting symptoms, and nutrition support received. RESULTS: A total of 103 patients were included (71% male, age: 58 ± 14 years, body mass index: 30±7 kg/m2), of whom 41.7% (n = 43) received mechanical ventilation within 14 days of ICU admission. While oral nutrition was received by more patients at any time point in the ICU (n = 93, 91.2% of patients) than enteral nutrition (EN) (n = 43, 42.2%) or parenteral nutrition (PN) (n = 2, 2.0%), EN was delivered for a greater duration of time (69.6% feeding days) than oral and PN (29.7% and 0.7%, respectively). More patients received oral intake than the other modes in the post-ICU ward (n = 95, 95.0%), and 40.0% (n = 38/95) of patients were receiving oral nutrition supplements. In the week after ICU discharge, 51.0% of patients (n = 51) had at least one nutrition-impacting symptom, most commonly a reduced appetite (n = 25; 24.5%) or dysphagia (n = 16; 15.7%). CONCLUSION: Critically ill patients during the COVID-19 pandemic in Australia were more likely to receive oral nutrition than artificial nutrition support at any time point both in the ICU and in the post-ICU ward, whereas EN was provided for a greater duration when it was prescribed. Nutrition-impacting symptoms were common.

Complications associated with prone positioning in mechanically ventilated COVID-19 patients: A multicentre, retrospective observational study.

BACKGROUND AND AIMS: Prone positioning is commonly applied to improve gas exchange in mechanically ventilated patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). Whilst prone positioning is effective, specific complications may arise. We aimed to assess the prevalence of specific complications related to prone positioning in patients mechanically ventilated for COVID-19-related ARDS. DESIGN: Multicentre, retrospective observational study. METHODS: Multi-centre observational study of mechanically ventilated patients with COVID-19-related ARDS admitted to intensive care units in Melbourne, Australia, from August to November 2021. Data on baseline characteristics, prone positioning, complications, and patient outcomes were collected. RESULTS: We assessed 553 prone episodes in 220 patients across seven sites (mean ± standard deviation age: 54 ± 13 years, 61% male). Overall, 58% (127/220) of patients experienced at least one prone-positioning-related complication. Pressure injury was the most prevalent (n = 92/220, 42%) complication reported. Factors associated with increased risk of pressure injury were male sex (adjusted odds ratio = 1.15, 95% confidence interval: [1.02-1.31]) and the total number of prone episodes (adjusted odds ratio = 1.11, 95% confidence interval: [1.07-1.15]). Device dislodgement was the next most common complication, occurring in 28 of 220 (13%) patients. There were no nerve or retinal injuries reported. CONCLUSIONS: Pressure injuries and line dislodgement were the most prevalent complications associated with prone positioning of patients mechanically ventilated for COVID-19. The risk of pressure injuries was associated with male sex and the number of prone positioning episodes.

Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19.

BACKGROUND: Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. METHODS: We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. RESULTS: A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent. CONCLUSIONS: Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).

Sodium Bicarbonate for Metabolic Acidosis in the ICU: Results of a Pilot Randomized Double-Blind Clinical Trial.

OBJECTIVES: To identify the best population, design of the intervention, and to assess between-group biochemical separation, in preparation for a future phase III trial. DESIGN: Investigator-initiated, parallel-group, pilot randomized double-blind trial. SETTING: Eight ICUs in Australia, New Zealand, and Japan, with participants recruited from April 2021 to August 2022. PATIENTS: Thirty patients greater than or equal to 18 years, within 48 hours of admission to the ICU, receiving a vasopressor, and with metabolic acidosis (pH < 7.30, base excess [BE] < -4 mEq/L, and Pa co2 < 45 mm Hg). INTERVENTIONS: Sodium bicarbonate or placebo (5% dextrose). MEASUREMENTS AND MAIN RESULT: The primary feasibility aim was to assess eligibility, recruitment rate, protocol compliance, and acid-base group separation. The primary clinical outcome was the number of hours alive and free of vasopressors on day 7. The recruitment rate and the enrollment-to-screening ratio were 1.9 patients per month and 0.13 patients, respectively. Time until BE correction (median difference, -45.86 [95% CI, -63.11 to -28.61] hr; p < 0.001) and pH correction (median difference, -10.69 [95% CI, -19.16 to -2.22] hr; p = 0.020) were shorter in the sodium bicarbonate group, and mean bicarbonate levels in the first 24 hours were higher (median difference, 6.50 [95% CI, 4.18 to 8.82] mmol/L; p < 0.001). Seven days after randomization, patients in the sodium bicarbonate and placebo group had a median of 132.2 (85.6-139.1) and 97.1 (69.3-132.4) hours alive and free of vasopressor, respectively (median difference, 35.07 [95% CI, -9.14 to 79.28]; p = 0.131). Recurrence of metabolic acidosis in the first 7 days of follow-up was lower in the sodium bicarbonate group (3 [20.0%] vs. 15 [100.0%]; p < 0.001). No adverse events were reported. CONCLUSIONS: The findings confirm the feasibility of a larger phase III sodium bicarbonate trial; eligibility criteria may require modification to facilitate recruitment.

Natural language processing diagnosed behavioural disturbance phenotypes in the intensive care unit: characteristics, prevalence, trajectory, treatment, and outcomes.

BACKGROUND: Natural language processing (NLP) may help evaluate the characteristics, prevalence, trajectory, treatment, and outcomes of behavioural disturbance phenotypes in critically ill patients. METHODS: We obtained electronic clinical notes, demographic information, outcomes, and treatment data from three medical-surgical ICUs. Using NLP, we screened for behavioural disturbance phenotypes based on words suggestive of an agitated state, a non-agitated state, or a combination of both. RESULTS: We studied 2931 patients. Of these, 225 (7.7%) were NLP-Dx-BD positive for the agitated phenotype, 544 (18.6%) for the non-agitated phenotype and 667 (22.7%) for the combined phenotype. Patients with these phenotypes carried multiple clinical baseline differences. On time-dependent multivariable analysis to compensate for immortal time bias and after adjustment for key outcome predictors, agitated phenotype patients were more likely to receive antipsychotic medications (odds ratio [OR] 1.84, 1.35-2.51, p < 0.001) compared to non-agitated phenotype patients but not compared to combined phenotype patients (OR 1.27, 0.86-1.89, p = 0.229). Moreover, agitated phenotype patients were more likely to die than other phenotypes patients (OR 1.57, 1.10-2.25, p = 0.012 vs non-agitated phenotype; OR 4.61, 2.14-9.90, p < 0.001 vs. combined phenotype). This association was strongest in patients receiving mechanical ventilation when compared with the combined phenotype (OR 7.03, 2.07-23.79, p = 0.002). A similar increased risk was also seen for patients with the non-agitated phenotype compared with the combined phenotype (OR 6.10, 1.80-20.64, p = 0.004). CONCLUSIONS: NLP-Dx-BD screening enabled identification of three behavioural disturbance phenotypes with different characteristics, prevalence, trajectory, treatment, and outcome. Such phenotype identification appears relevant to prognostication and trial design.

Spin and fragility in anaesthesia studies: when sirens sing into anaesthetists' ears.

Spin and fragility are common in randomised controlled trials published in anaesthesia journals. Staying with the facts and addressing only the primary endpoint in the conclusion of clinical research reports might help reduce spin. Routinely reporting the fragility index, in turn, could deliver information about robustness, enhancing the transparency of positive dichotomous results. It is in the best interest of clinical research that authors, reviewers, and journals come together to reduce spin and address the fragility of randomised controlled trials.

Extracorporeal membrane oxygenation for critically ill adults.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) may provide benefit in certain populations of adults, including those with severe cardiac failure, severe respiratory failure, and cardiac arrest. However, it is also associated with serious short- and long-term complications, and there remains a lack of high-quality evidence to guide practice. Recently several large randomized controlled trials (RCTs) have been published, therefore, we undertook an update of our previous systematic review published in 2014. OBJECTIVES: To evaluate whether venovenous (VV), venoarterial (VA), or ECMO cardiopulmonary resuscitation (ECPR) improve mortality compared to conventional cardiopulmonary support in critically ill adults. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was March 2022. The search was limited to English language only. SELECTION CRITERIA: We included RCTs, quasi-RCTs, and cluster-RCTs that compared VV ECMO, VA ECMO or ECPR to conventional support in critically ill adults. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcome was 1. all-cause mortality at day 90 to one year. Our secondary outcomes were 2. length of hospital stay, 3. survival to discharge, 4. disability, 5. adverse outcomes/safety events, 6. health-related quality of life, 7. longer-term health status, and 8. cost-effectiveness. We used GRADE to assess certainty of evidence. MAIN RESULTS: Five RCTs met our inclusion criteria, with four new studies being added to the original review (total 757 participants). Two studies were of VV ECMO (429 participants), one VA ECMO (41 participants), and two ECPR (285 participants). Four RCTs had a low risk of bias and one was unclear, and the overall certainty of the results (GRADE score) was moderate, reduced primarily due to indirectness of the study populations and interventions. ECMO was associated with a reduction in 90-day to one-year mortality compared to conventional treatment (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.70 to 0.92; P = 0.002, I2 = 11%). This finding remained stable after performing a sensitivity analysis by removing the single trial with an uncertain risk of bias. Subgroup analyses did not reveal a significant subgroup effect across VV, VA, or ECPR modes (P = 0.73). Four studies reported an increased risk of major hemorrhage with ECMO (RR 3.32, 95% CI 1.90 to 5.82; P < 0.001), while two studies reported no difference in favorable neurologic outcome (RR 2.83, 95% CI 0.36 to 22.42; P = 0.32). Other secondary outcomes were not consistently reported across the studies. AUTHORS' CONCLUSIONS: In this updated systematic review, which included four additional RCTs, we found that ECMO was associated with a reduction in day-90 to one-year all-cause mortality, as well as three times increased risk of bleeding. However, the certainty of this result was only low to moderate, limited by a low number of small trials, clinical heterogeneity, and indirectness across studies.

Impact of Intensity of Continuous Renal Replacement Therapy on Duration of Ventilation in Critically Ill Patients: A Secondary Analysis of the RENAL Trial.

INTRODUCTION: More intensive renal replacement therapy (RRT) has been associated with prolonged mechanical ventilation (MV). However, such finding may be dependent on RRT modality. We hypothesized that, when using continuous renal replacement therapy (CRRT), RRT intensity would not be associated with prolonged MV. METHODS: In a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement trial comparing different CRRT intensities, we applied Fine-Gray competing risk analysis with time to successful extubation within 28 days as primary outcome. RESULTS: We studied 531 patients in the higher intensity and 551 in the lower intensity group. Higher intensity patients had more hypophosphatemia (66.7 vs. 58.1%; p = 0.004) and more days with hypophosphatemia (2.2 ± 2.8 vs. 1.6 ± 2.2; p < 0.001). There was no difference in the number of patients extubated within 28 days (60.1% vs. 62.4%; adjusted subdistribution hazard ratio [SHR], 0.95 [95% CI, 0.86 to 1.06]) or time to extubation (8 [5-16] vs. 8 [5-15] days; adjusted median difference, 0.65 [95% CI, -0.41 to 1.70]). Among patients from the upper tertile of days with hypophosphatemia, higher intensity CRRT was associated with a lower chance of successful extubation within 28 days (SHR, 0.67 [95% CI, 0.55 to 0.82]; p for heterogeneity = 0.013). CONCLUSIONS: In the RENAL trial, higher intensity CRRT was not associated with delayed extubation. However, it was associated with a greater rate of hypophosphatemia and more days with hypophosphatemia was associated with a lower chance of successful extubation.