OBJECTIVE: To discuss the strengths and limitations of ventilator-free days and to provide a comprehensive discussion of the different analytic methods for analyzing and interpreting this outcome. METHODS: Using simulations, the power of different analytical methods was assessed, namely: quantile (median) regression, cumulative logistic regression, generalized pairwise comparison, conditional approach and truncated approach. Overall, 3,000 simulations of a two-arm trial with n = 300 per arm were computed using a two-sided alternative hypothesis and a type I error rate of α = 0.05. RESULTS: When considering power, median regression did not perform well in studies where the treatment effect was mainly driven by mortality. Median regression performed better in situations with a weak effect on mortality but a strong effect on duration, duration only, and moderate mortality and duration. Cumulative logistic regression was found to produce similar power to the Wilcoxon rank-sum test across all scenarios, being the best strategy for the scenarios of moderate mortality and duration, weak mortality and strong duration, and duration only. CONCLUSION: In this study, we describe the relative power of new methods for analyzing ventilator-free days in critical care research. Our data provide validation and guidance for the use of the cumulative logistic model, median regression, generalized pairwise comparisons, and the conditional and truncated approach in specific scenarios.
Critical Care , Respiration, Artificial , Humans , Critical Care/methods , Respiration, Artificial/mortality , Logistic Models , Time Factors , Computer Simulation , Ventilator Weaning/methods
PURPOSE: During continuous renal replacement therapy (CRRT), a high net ultrafiltration rate (NUF) may worsen the decrease in urine output (UO) associated with starting CRRT. However, fluid balance (FB) may modulate this association. We aimed to examine the relationship between NUF, UO and FB at the start of CRRT. METHODS: A retrospective cohort study of 1030 CRRT-treated patients admitted to two tertiary ICUs. RESULTS: Median age was 60 years (IQR, 48-70), median APACHE III was 94 (IQR, 76-114) and median NUF rate was 0.7 mL/kg/h. In the 24 h after CRRT started, the mean hourly UO decreased from 25.5 mL to 11.9 mL (P < 0.001). Moreover, after adjusting for multiple confounders on multivariable analysis, a higher NUF was not significantly associated with a lower UO (-1.5 mL/kg for every 1 mL/kg/h increase in NUF; 95% CI -3.1 to 0.04; p = 0.064). In addition, pre-CRRT FB did not modulate the above relationship between higher NUF and lower UO. CONCLUSION: A higher NUF rate was not significantly associated with a greater immediate and sustained reduction in UO after CRRT commencement. FB before CRRT was also not associated with a greater reduction in UO. These findings do not provide evidence for an effect of NUF on renal function.
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 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 a lower number of days alive and out of 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, days alive and out of 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 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 [CI], 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 hospital at day 180 but it increased 180-day mortality.
INTRODUCTION: Acute respiratory distress syndrome (ARDS), marked by acute hypoxemia and bilateral pulmonary infiltrates, has been defined in multiple ways since its first description. This Delphi study aims to collect global opinions on the conceptual framework of ARDS, assess the usefulness of components within current and past definitions and investigate the role of subphenotyping. The varied expertise of the panel will provide valuable insights for refining future ARDS definitions and improving clinical management. METHODS: A diverse panel of 35-40 experts will be selected based on predefined criteria. Multiple choice questions (MCQs) or 7-point Likert-scale statements will be used in the iterative Delphi rounds to achieve consensus on key aspects related to the utility of definitions and subphenotyping. The Delphi rounds will be continued until a stable agreement or disagreement is achieved for all statements. ANALYSIS: Consensus will be considered as reached when a choice in MCQs or Likert-scale statement achieved ≥80% of votes for agreement or disagreement. The stability will be checked by non-parametric χ2 tests or Kruskal Wallis test starting from the second round of Delphi process. A p-value ≥0.05 will be used to define stability. ETHICS AND DISSEMINATION: The study will be conducted in full concordance with the principles of the Declaration of Helsinki and will be reported according to CREDES guidance. This study has been granted an ethical approval waiver by the NMC Healthcare Regional Research Ethics Committee, Dubai (NMCHC/CR/DXB/REC/APP/002), owing to the nature of the research. Informed consent will be obtained from all panellists before the start of the Delphi process. The study will be published in a peer-review journal with the authorship agreed as per ICMJE requirements. TRIAL REGISTRATION NUMBER: NCT06159465.
Consensus , Delphi Technique , Respiratory Distress Syndrome , Humans , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/therapy , Research Design
PURPOSE: A positive fluid balance (FB) is associated with harm in intensive care unit (ICU) patients with acute kidney injury (AKI). We aimed to understand how a positive balance develops in such patients. METHODS: Multinational, retrospective cohort study of critically ill patients with AKI not requiring renal replacement therapy. RESULTS: AKI occurred at a median of two days after admission in 7894 (17.3%) patients. Cumulative FB became progressively positive, peaking on day three despite only 848 (10.7%) patients receiving fluid resuscitation in the ICU. In those three days, persistent crystalloid use (median:60.0 mL/h; IQR 28.9-89.2), nutritional intake (median:18.2 mL/h; IQR 0.0-45.9) and limited urine output (UO) (median:70.8 mL/h; IQR 49.0-96.7) contributed to a positive FB. Although UO increased each day, it failed to match input, with only 797 (10.1%) patients receiving diuretics in ICU. After adjustment, a positive FB four days after AKI diagnosis was associated with an increased risk of hospital mortality (OR 1.12;95% confidence intervals 1.05-1.19;p-value <0.001). CONCLUSION: Among ICU patients with AKI, cumulative FB increased after diagnosis and was associated with an increased risk of mortality. Continued crystalloid administration, increased nutritional intake, limited UO, and minimal use of diuretics all contributed to positive FB. KEY POINTS: Question How does a positive fluid balance develop in critically ill patients with acute kidney injury? Findings Cumulative FB increased after AKI diagnosis and was secondary to persistent crystalloid fluid administration, increasing nutritional fluid intake, and insufficient urine output. Despite the absence of resuscitation fluid and an increasing cumulative FB, there was persistently low diuretics use, ongoing crystalloid use, and a progressive escalation of nutritional fluid therapy. Meaning Current management results in fluid accumulation after diagnosis of AKI, as a result of ongoing crystalloid administration, increasing nutritional fluid, limited urine output and minimal diuretic use.
PURPOSE: To perform a post-hoc reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) and the Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients (RENAL) trials through hierarchical composite endpoint analysis using win ratio (WR). MATERIAL AND METHODS: All patients with complete information from the STARRT-AKI (which compared accelerated versus standard approaches for renal replacement therapy - RRT initiation) and RENAL (which compared two different RRT doses in critically ill patients) trials were selected. WR was defined as a hierarchical composite endpoint using 90-day mortality, RRT dependency at 90-days, intensive care unit (ICU) length-of-stay (LOS), and hospital LOS (primary analysis); values above the unit represent a benefit of the intervention for the hierarchical composite endpoint. A secondary analysis replacing LOS by days alive and free of RRT was performed. Stratified analyses were performed according to illness severity score, surgical status, and the presence of sepsis. RESULTS: The WR analysis produced 2,141,830 pairs for the STARRT-AKI trial and 536,446 pairs for the RENAL trial, respectively. The WR results for STARRT-AKI and RENAL were 1.04 (95% confidence interval [CI] 0.96-1.13; p = 0.33) and 1.02 (95% CI; 0.90-1.15; p = 0.75) for the primary analysis, and 0.88 (95% CI; 0.79-0.99; p = 0.03) and 1.02 (95% CI; 0.87-1.21; p = 0.77) for the secondary analysis, respectively. The stratified analysis of the primary suggested possible benefit of the accelerated-strategy in the STARRT-AKI trial for non-surgical patients with sepsis, while the secondary analysis suggested possible harm of the accelerated-strategy for surgical patients without sepsis. There was no evidence of heterogeneity in treatment effects in stratified analyses in the RENAL trial. CONCLUSION: WR approach using a hierarchical composite endpoint is feasible for trials in critical care nephrology. The primary re-analyses of the STARRT-AKI and RENAL trials both yielded neutral results; however, there was suggestion of heterogeneity in treatment effect in stratified analyses of the STARRT-AKI trial by surgical status and sepsis. Selection of the endpoints and hierarchical ordering before trial design using the WR approach can have important implications for trial interpretation. TRIAL REGISTRY: ClinicalTrials.gov number NCT02568722 (STARRT-AKI) and NCT00076219 (RENAL).
BACKGROUND: Mobilisation during critical illness is now included in multiple clinical practice guidelines. However, a large, randomised trial and systematic review have recently identified an increased probability of adverse events and mortality in patients who received early active mobilisation in the intensive care unit (ICU). We aimed to determine the effects of mobilisation compared with usual care on adverse events and mortality in an acute ICU setting. In subgroup analyses, we specifically aimed to investigate possible sources of harm, including the timing and duration of mobilisation achieved, ventilation status, and admission diagnosis. METHODS: In this systematic review with frequentist and Bayesian analyses, we searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, SPORTDiscus, SCOPUS, Web of Science, and PEDro electronic databases, as well as clinical trial registries (ICTRP and ClinicalTrials.gov), from inception to March 16, 2023, without language restrictions. Eligible studies were randomised controlled trials that examined active mobilisation compared with either no mobilisation or mobilisation commencing later, or at a lower frequency or intensity, in adults who were critically ill during or after a period of mechanical ventilation in an acute ICU setting. Two authors independently screened reports, extracted data, and assessed the risk of bias using the Cochrane risk-of-bias tool (version 1). The primary outcome was the number of adverse events that occurred during the implementation of mobilisation, with the effect of mobilisation on mortality being the secondary outcome. Risk ratios (RRs) with 95% CIs were calculated in R (version 4.0.3) using random-effects modelling, with Bayesian analysis completed to calculate the probability of treatment harm (ie, RR >1). Subgroup analyses were completed to investigate the association of various factors of mobilisation on adverse events and mortality: duration of mobilisation (longer [≥20 min per day] vs shorter [<20 min per day]), timing of commencement (early [≤72 h from ICU admission] vs late [>72 h from ICU admission]), ventilation status at commencement (all patients mechanically ventilated vs all patients extubated), and ICU admission diagnosis (surgical vs medical). This study was registered with PROSPERO, CRD42022369272. FINDINGS: After title and abstract screening of 14 440 studies and review of 466 full texts, 67 trials with 7004 participants met inclusion criteria, with 59 trials contributing to the meta-analysis. Of the 67 included studies, 15 (22%) did not mention adverse events and 13 (19%) reported no adverse events occurring across the trial period. Overall, we found no effect of mobilisation compared with usual care on the occurrence of adverse events (RR 1·09 [95% CI 0·69-1·74], p=0·71; I2 91%; 32 731 events, 20 studies; very low certainty), with a 2·96% occurrence rate (693 events in 23 395 intervention sessions; 25 studies). Mobilisation did not have any effect on mortality (RR 0·98 [95% CI 0·87-1·12], p=0·81; I2 0%; n=6218, 58 studies; moderate certainty). Subgroup analysis was hindered by the large amount of data that could not be allocated and analysed, making the results hypothesis generating only. INTERPRETATION: Implementation of mobilisation in the ICU was associated with a less than 3% chance of an adverse event occurring and was not found to increase adverse events or mortality overall, providing reassurance for clinicians about the safety of performing this intervention. Subgroup analyses did not clearly identify any specific variable of mobilisation implementation that increased harm. FUNDING: None.
Critical Illness , Early Ambulation , Intensive Care Units , Respiration, Artificial , Humans , Respiration, Artificial/statistics & numerical data , Respiration, Artificial/adverse effects , Intensive Care Units/statistics & numerical data , Early Ambulation/methods , Early Ambulation/adverse effects , Critical Illness/mortality , Critical Illness/therapy , Bayes Theorem , Randomized Controlled Trials as Topic , Male , Female
OBJECTIVES: Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant. DESIGN: Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722). SETTING: One hundred-fifty-three ICUs in 13 countries. PATIENTS: Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ (p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ (p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU (p < 0.001) and hospital discharge (p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], -11.3%; 95% CI, -17.7% to -4.8%; p < 0.001 and for ANZ vs. North America: RD, -10.3%; 95% CI, -17.5% to -3.1%; p = 0.007). CONCLUSIONS: Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions.
Acute Kidney Injury , Intensive Care Units , Renal Replacement Therapy , Humans , Acute Kidney Injury/therapy , Male , Renal Replacement Therapy/methods , Renal Replacement Therapy/statistics & numerical data , Female , Middle Aged , New Zealand , North America , Aged , Australia , Europe , Critical Illness/therapy , Treatment Outcome
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.
COVID-19 , Critical Illness , Adult , Humans , Male , Middle Aged , Aged , Female , COVID-19 Testing , Pandemics , Energy Intake , Length of Stay , Australia , Hospitalization , Intensive Care Units
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.
Hospital Rapid Response Team , Hospitalization , Humans , Hospital Mortality , Vital Signs/physiology , Retrospective Studies , Intensive Care Units , Emergency Service, Hospital , Hospitals, Teaching
The cardiovascular safety from azithromycin in the treatment of several infectious diseases has been challenged. In this prespecified pooled analysis of 2 multicenter randomized clinical trials, we aimed to assess whether the use of azithromycin might lead to corrected QT (QTc) interval prolongation or clinically relevant ventricular arrhythmias. In the COALITION COVID Brazil I trial, 667 patients admitted with moderate COVID-19 were randomly allocated to hydroxychloroquine, hydroxychloroquine plus azithromycin, or standard of care. In the COALITION COVID Brazil II trial, 447 patients with severe COVID-19 were randomly allocated to hydroxychloroquine alone versus hydroxychloroquine plus azithromycin. The principal end point for the present analysis was the composite of death, resuscitated cardiac arrest, or ventricular arrhythmias. The addition of azithromycin to hydroxychloroquine did not result in any prolongation of the QTc interval (425.8 ± 3.6 ms vs 427.9 ± 3.9 ms, respectively, mean difference -2.1 ms, 95% confidence interval -12.5 to 8.4 ms, p = 0.70). The combination of azithromycin plus hydroxychloroquine compared with hydroxychloroquine alone did not result in increased risk of the primary end point (proportion of patients with events at 15 days 17.2% vs 16.0%, respectively, hazard ratio 1.08, 95% confidence interval 0.78 to 1.49, p = 0.65). In conclusion, in patients hospitalized with COVID-19 already receiving standard-of-care management (including hydroxychloroquine), the addition of azithromycin did not result in the prolongation of the QTc interval or increase in cardiovascular adverse events. Because azithromycin is among the most commonly prescribed antimicrobial agents, our results may inform clinical practice. Clinical Trial Registration: NCT04322123, NCT04321278.
COVID-19 , Long QT Syndrome , Humans , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/epidemiology , Arrhythmias, Cardiac/drug therapy , Azithromycin/adverse effects , COVID-19 Drug Treatment , Electrocardiography/methods , Hydroxychloroquine/therapeutic use , Long QT Syndrome/chemically induced , Randomized Controlled Trials as Topic , SARS-CoV-2
BACKGROUND: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated. METHODS: DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study. CONCLUSION: DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients. CLINICALTRIALS.GOV REGISTRY: NCT05558098.
Critical Illness , Sodium-Glucose Transporter 2 Inhibitors , Adult , Humans , Critical Illness/therapy , Multiple Organ Failure/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Multicenter Studies as Topic
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.
Intensive Care Units , Natural Language Processing , Humans , Prevalence , Respiration, Artificial , Phenotype
INTRODUCTION: Awake prone positioning has the potential to improve oxygenation and decrease respiratory rate, potentially reducing the need for intubation in patients with acute hypoxemic respiratory failure. We investigated awake prone positioning-induced changes in oxygenation and respiratory rate, and the prognostic capacity for intubation in patients with COVID-19 pneumonia. METHODS: International multicenter prospective observation study in critically ill adult patients with COVID-19 receiving supplemental oxygen. We collected data on oxygenation and respiratory rate at baseline, and at 1 h after being placed in prone positioning. The combined primary outcome was oxygenation and respiratory rate at 1 h. The secondary endpoint was treatment failure, defined as need for intubation within 24 h of start of awake prone positioning. RESULTS: Between March 27th and November 2020, 101 patients were enrolled of which 99 were fully analyzable. Awake prone positioning lasted mean of 3 [2-4] h. In 77 patients (77.7%), awake prone positioning improved oxygenation, and in 37 patients (54.4%) it decreased respiratory rate. Twenty-nine patients (29.3%) were intubated within 24 h. An increase in SpO2/FiO2 of < 10 (OR 5.1, 95% CI 1.4-18.5, P = 0.01), a failure to increase PaO2/FiO2 to > 116 mmHg (OR 3.6, 95% CI 1.2-10.8, P = 0.02), and a decrease in respiratory rate of < 2 breaths/min (OR 3.6, 95% CI 1.3-9.5, P = 0.01) were independent variables associated with need for intubation. The AUC-ROC curve for intubation using a multivariable model was 0.73 (95% CI 0.62-0.84). CONCLUSIONS: Awake prone positioning improves oxygenation in the majority of patients, and decreases respiratory rate in more than half of patients with acute hypoxemic respiratory failure caused by COVID-19. One in three patients need intubation within 24 h. Awake prone position-induced changes in oxygenation and respiratory rate have prognostic capacity for intubation within 24 h.
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.
Acute Kidney Injury , Continuous Renal Replacement Therapy , Hypophosphatemia , Humans , Critical Illness/therapy , Renal Replacement Therapy/adverse effects , Hypophosphatemia/etiology , Proportional Hazards Models , Acute Kidney Injury/therapy
Objective: This article aims to describe the epidemiology of decompensated metabolic acidosis, the characteristics of sodium bicarbonate (SB) administration and outcomes in emergency department (ED) patients. Design: This is a retrospective cohort study. Setting: ED of a tertiary referral hospital in Melbourne, Australia. Participants: Adult patients presenting to the ED between 1 July 2011 and 20 September 2020 with decompensated metabolic acidosis diagnosed on arterial blood gas (ABG). Main outcome measures: We compared characteristics between those treated with or without SB. We studied SB administration characteristics, change in laboratory variables, factors associated with use and dose, and clinical outcomes. Results: Among 753,613 ED patients, 314 had decompensated metabolic acidosis on ABG, with 17.8% receiving SB. Patients in the SB group had lower median pH, CO2, bicarbonate, and base excess (BE) levels compared with the No SB group (P < 0.01). The median number of SB doses in the SB group was one treatment. This was given at a median total dose of 100 mmol and at a median of 2.8 h after the diagnostic blood gas results. Only 42% of patients in the SB group had a subsequent blood gas measured. In such patients, there was no significant change in pH, bicarbonate, or BE. SB therapy was not independently associated with mortality. Conclusions: ABG-confirmed decompensated metabolic acidosis was rare but associated with a high mortality. SB administration occurred in a minority of patients and in more acidaemic patients. However, SB dose was stereotypical and not tailored to acidosis severity. Assessment of SB effect was infrequent and showed no correction of acidosis. Systematic studies of titrated SB therapy are required to inform current practice.
