Physiological changes after fluid bolus therapy in cardiac surgery patients: A propensity score matched case-control study.

Objective: Fluid bolus therapy (FBT) is ubiquitous in intensive care units (ICUs) after cardiac surgery. However, its physiological effects remain unclear. Design: : We performed an electronic health record-based quasi-experimental ICU study after cardiac surgery. We applied propensity score matching and compared the physiological changes after FBT episodes to matched control episodes where despite equivalent physiology no fluid bolus was given. Setting: The study was conducted in a multidisciplinary ICU of a tertiary-level academic hospital. Participants: The study included 2,736 patients who underwent Coronary Artery Bypass Grafting and/or heart valve surgery. Main Outcome Measures: Changes in cardiac output (CO) and mean arterial pressure (MAP) during the 60 minutes following FBT. Results: We analysed 3572 matched fluid bolus (FB) episodes. After FBT, but not in control episodes, CO increased within 10 min, with a maximum increase of 0.2 l/min (95%CI 0.1 to 0.2) or 4% above baseline at 40 min (p < 0.0001 vs. controls). CO increased by > 10% from baseline in 60.6% of FBT and 49.1% of control episodes (p < 0.0001). MAP increased by > 10% in 51.7% of FB episodes compared to 53.4% of controls. Finally, FBT was not associated with changes in acid-base status or oxygen delivery. Conclusion: In this quasi-experimental comparative ICU study in cardiac surgery patients, FBT was associated with statistically significant but numerically small increases in CO. Nearly half of FBT failed to induce a positive CO or MAP response.

Hospital and long-term opioid use according to analgosedation with fentanyl vs. morphine: Findings from the ANALGESIC trial.

Objectives: Opioid use disorder is extremely common. Many long-term opioid users will have their first exposure to opioids in hospitals. We aimed to compare long-term opioid use in patients who received fentanyl vs. morphine analgosedation and assess ICU related risk factors for long-term opioid use. Design: We performed a post-hoc analysis of the Assessment of Opioid Administration to Lead to Analgesic Effects and Sedation in Intensive Care (ANALGESIC) cluster randomised crossover trial of fentanyl and morphine infusions for analgosedation in mechanically ventilated patients. Setting: Two mixed, adult, university affiliated intensive care units in Melbourne, Australia. Participants: Adult patients who were mechanically ventilated and received fentanyl or morphine for analgosedation in the ANALGESIC trial. Main outcome measures: We assessed discharge and long-term (90-365 days) opioid use in opioid-naïve patients at hospital admission according to the agent used for analgosedation. Results: We studied 477 patients (242 fentanyl and 235 morphine). There were no differences between discharge (16.5% vs. 14.0%, p = 0.45), 90-180 day post-discharge use (3.7% vs 2.1%, p = 0.30) or 180-365 day post-discharge use (3.4% vs 1.3%, p = 0.22) of opioids when comparing those patients who received fentanyl vs. those who received morphine. Surgical diagnosis and one chronic condition were associated with increased hospital discharge prescription of opioids, whereas increasing APACHE II score was associated with decreased discharge prescription. No ICU-related factors were associated with long-term opioid use. Conclusions: Approximately one in seven opioid-naïve patients who receive analgosedation for mechanical ventilation in ICU will be prescribed opioid medications at hospital discharge. There was no difference in discharge prescription or long-term use of opioids depending on whether fentanyl or morphine was used for analgosedation.

Current fluid management practice in critically ill adults on continuous renal replacement therapy: A binational, observational study.

Introduction In critically ill patients undergoing continuous renal replacement therapy (CRRT), a positive fluid balance (FB) is associated with adverse outcomes. However, current FB management practices in CRRT patients are poorly understood. We aimed to study FB and its components in British and Australian CRRT patients to inform future trials. Methods We obtained detailed electronic health record data on all fluid-related variables during CRRT and hourly FB for the first seven days of treatment. Results We studied 1,616 patients from three tertiary ICUs in two countries. After the start of CRRT, the mean cumulative FB became negative at 31 hours and remained negative over seven days to a mean nadir of -4.1 L (95% confidence intervals (CI) of -4.6 to -3.5). The net ultrafiltration (NUF) rate was the dominant fluid variable (-67.7 mL/h; SD 75.7); however, residual urine output (-34.7 mL/h; SD 54.5), crystalloid administration (48.1 mL/h; SD 44.6), and nutritional input (36.4 mL/h; SD 29.7) significantly contributed to FB. Patients with a positive FB after 72 hours of CRRT, were more severely ill, required high-dose vasopressors and had high lactate concentrations (5.0 mmol/L; IQR 2.3 - 10.5). A positive FB was independently associated with increased hospital mortality (OR 1.70; 95% CI; p=0.004). Conclusion In the study ICUs, most CRRT patients achieved a predominantly NUF-dependent negative FB. Patients with a positive FB at 72 hours had greater illness severity and haemodynamic instability. Achieving equipoise for conducting trials that target a negative early FB in such patients may be difficult.

Different ventilation intensities among various categories of patients ventilated for reasons other than ARDS--A pooled analysis of 4 observational studies.

PURPOSE: We investigated driving pressure (ΔP) and mechanical power (MP) and associations with clinical outcomes in critically ill patients ventilated for reasons other than ARDS. MATERIALS AND METHODS: Individual patient data analysis of a pooled database that included patients from four observational studies of ventilation. ΔP and MP were compared among invasively ventilated non-ARDS patients with sepsis, with pneumonia, and not having sepsis or pneumonia. The primary endpoint was ΔP; secondary endpoints included MP, ICU mortality and length of stay, and duration of ventilation. RESULTS: This analysis included 372 (11%) sepsis patients, 944 (28%) pneumonia patients, and 2040 (61%) patients ventilated for any other reason. On day 1, median ΔP was higher in sepsis (14 [11-18] cmH2O) and pneumonia patients (14 [11-18]cmH2O), as compared to patients not having sepsis or pneumonia (13 [10-16] cmH2O) (P < 0.001). Median MP was also higher in sepsis and pneumonia patients. ΔP, as opposed to MP, was associated with ICU mortality in sepsis and pneumonia patients. CONCLUSIONS: The intensity of ventilation differed between patients with sepsis or pneumonia and patients receiving ventilation for any other reason; ΔP was associated with higher mortality in sepsis and pneumonia patients. REGISTRATION: This post hoc analysis was not registered; the individual studies that were merged into the used database were registered at clinicaltrials.gov: NCT01268410 (ERICC), NCT02010073 (LUNG SAFE), NCT01868321 (PRoVENT), and NCT03188770 (PRoVENT-iMiC).

Dose equivalence for metaraminol and noradrenaline - A retrospective analysis.

BACKGROUND: Noradrenaline and metaraminol are commonly used vasopressors in critically ill patients. However, little is known of their dose equivalence. METHODS: We conducted a single centre retrospective cohort study of all ICU patients who transitioned from metaraminol to noradrenaline infusions between August 26, 2016 and December 31, 2020. Patients receiving additional vasoactive drug infusion were excluded. Dose equivalence was calculated based on the last hour metaraminol dose (in µg/min) and the first hour noradrenaline dose (in µg/min) with the closest matched mean arterial pressure (MAP). Sensitivity analyses were performed on patients with acute kidney injury (AKI), sepsis and mechanical ventilation. RESULTS: We studied 195 patients. The median conversion ratio of metaraminol to noradrenaline was 12.5:1 (IQR 7.5-20.0) for the overall cohort. However, the coefficient of variation was 77% and standard deviation was 11.8. Conversion ratios were unaffected by sepsis or mechanical ventilation but increased (14:1) with AKI. One in five patients had a MAP decrease of >10 mmHg during the transition period from metaraminol to noradrenaline. Post-transition noradrenaline dose (p < 0.001) and AKI (p = 0.045) were independently associated with metaraminol dose. The proportion of variation in noradrenaline dose predicted from metaraminol dose was low (R2 = 0.545). CONCLUSIONS: The median dose equivalence for metaraminol and noradrenaline in this study was 12.5:1. However, there was significant variance in dose equivalence, only half the proportion of variation in noradrenaline infusion dose was predicted by metaraminol dose, and conversion-associated hypotension was common.

A chromatin-regulated biphasic circuit coordinates IL-1ß-mediated inflammation.

Inflammation is characterized by a biphasic cycle consisting initially of a proinflammatory phase that is subsequently resolved by anti-inflammatory processes. Interleukin-1ß (IL-1ß) is a master regulator of proinflammation and is encoded within the same topologically associating domain (TAD) as IL-37, which is an anti-inflammatory cytokine that opposes the function of IL-1ß. Within this TAD, we identified a long noncoding RNA called AMANZI, which negatively regulates IL-1ß expression and trained immunity through the induction of IL37 transcription. We found that the activation of IL37 occurs through the formation of a dynamic long-range chromatin contact that leads to the temporal delay of anti-inflammatory responses. The common variant rs16944 present in AMANZI augments this regulatory circuit, predisposing individuals to enhanced proinflammation or immunosuppression. Our work illuminates a chromatin-mediated biphasic circuit coordinating expression of IL-1ß and IL-37, thereby regulating two functionally opposed states of inflammation from within a single TAD.

Magnitude and time to peak oxygenation effect of prone positioning in ventilated adults with COVID-19 related acute hypoxemic respiratory failure.

BACKGROUND: Prone positioning may improve oxygenation in acute hypoxemic respiratory failure and was widely adopted in COVID-19 patients. However, the magnitude and timing of its peak oxygenation effect remain uncertain with the optimum dosage unknown. Therefore, we aimed to investigate the magnitude of the peak effect of prone positioning on the PaO2 :FiO2 ratio during prone and secondly, the time to peak oxygenation. METHODS: Multi-centre, observational study of invasively ventilated adults with acute hypoxemic respiratory failure secondary to COVID-19 treated with prone positioning. Baseline characteristics, prone positioning and patient outcome data were collected. All arterial blood gas (ABG) data during supine, prone and after return to supine position were analysed. The magnitude of peak PaO2 :FiO2 ratio effect and time to peak PaO2 :FIO2 ratio effect was measured. RESULTS: We studied 220 patients (mean age 54 years) and 548 prone episodes. Prone positioning was applied for a mean (±SD) 3 (±2) times and 16 (±3) hours per episode. Pre-proning PaO2 :FIO2 ratio was 137 (±49) for all prone episodes. During the first episode. the mean PaO2 :FIO2 ratio increased from 125 to a peak of 196 (p < .001). Peak effect was achieved during the first episode, after 9 (±5) hours in prone position and maintained until return to supine position. CONCLUSIONS: In ventilated adults with COVID-19 acute hypoxemic respiratory failure, peak PaO2 :FIO2 ratio effect occurred during the first prone positioning episode and after 9 h. Subsequent episodes also improved oxygenation but with diminished effect on PaO2 :FIO2 ratio. This information can help guide the number and duration of prone positioning episodes.

The effect of age on clinical dose equivalency of fentanyl and morphine analgosedation in mechanically ventilated patients: Findings from the ANALGESIC trial.

BACKGROUND: The dose equivalency of fentanyl vs. morphine is widely considered to be approximately 1:100. However, little is known about the effect of age on this ratio when these agents are used as infusions for analgosedation. OBJECTIVES: To assess the impact of age on the clinical dose equivalency of fentanyl and morphine when used as infusions for analgosedation in mechanically ventilated intensive care unit patients. METHODS: We performed a post hoc analysis of the Assessment of Opioid Administration to Lead to Analgesic Effects and Sedation in Intensive Care (ANALGESIC) cluster randomised crossover trial of fentanyl and morphine infusions for analgosedation. Dose and analgosedative clinical equivalency of fentanyl and morphine were assessed by age and by using different body-size descriptors. RESULTS: We studied 663 patients (338 fentanyl, 325 morphine). Median (interquartile range) hourly dose of fentanyl and morphine were 58.1 (40.0-89.2) mcg and 3400 (2200-5000) mcg, respectively. The ratio of total dose of fentanyl:morphine was 1:93 in the 18- to 29-year-old group and 1:25 in the ≥80-year-old group (p = 0.015), respectively, with fentanyl becoming relatively less clinically effective as age increased. This effect was also seen when comparing dosing by different body-size descriptors with the strongest age-related change when using body surface area as body-size descriptor (p = 0.009). CONCLUSION: The analgosedative clinical dose equivalency of fentanyl vs. morphine is heterogeneous when used as infusions for analgosedation, with fentanyl becoming relatively less clinically effective as age increases. This information can help guide prescription of these agents during transition from one agent to the other in critically ill patients.

Neuromuscular blockade and oxygenation changes during prone positioning in COVID-19.

PURPOSE: Neuromuscular blockers (NMBs) are often used during prone positioning to facilitate mechanical ventilation in COVID-19 related ARDS. However, their impact on oxygenation is uncertain. METHODS: Multi-centre observational study of invasively ventilated COVID-19 ARDS adults treated with prone positioning. We collected data on baseline characteristics, prone positioning, NMB use and patient outcome. We assessed arterial blood gas data during supine and prone positioning and after return to the supine position. RESULTS: We studied 548 prone episodes in 220 patients (mean age 54 years, 61% male) of whom 164 (75%) received NMBs. Mean PaO2:FiO2 (P/F ratio) during the first prone episode with NMBs reached 208 ± 63 mmHg compared with 161 ± 66 mmHg without NMBs (Δmean = 47 ± 5 mmHg) for an absolute increase from baseline of 76 ± 56 mmHg versus 55 ± 56 mmHg (padj < 0.001). The mean P/F ratio on return to the supine position was 190 ± 63 mmHg in the NMB group versus 141 ± 64 mmHg in the non-NMB group for an absolute increase from baseline of 59 ± 58 mmHg versus 34 ± 56 mmHg (padj < 0.001). CONCLUSION: During prone positioning, NMB is associated with increased oxygenation compared to non-NMB therapy, with a sustained effect on return to the supine position. These findings may help guide the use of NMB during prone positioning in COVID-19 ARDS.

Intensive care unit admission from the emergency department in the setting of National Emergency Access Targets.

Purpose: Since the introduction of National Emergency Access Targets (NEATs) in 2012 there has been little research examining patients admitted to the intensive care unit (ICU).We assessed differences in baseline characteristics and outcomes of patients admitted from the Emergency Department (ED) to the ICU within 4 hours compared with patients who were not. Methods: This retrospective observational study included all adults (≥18 years old) admitted to the ICU from the ED of Austin Hospital, Melbourne, Australia, between 1 January 2017 and 31st December 2019 inclusive. Results: 1544 patients were admitted from the ED to the ICU and 65% had an ED length of stay (EDLOS) > 4 hour. Such patients were more likely to be older, female, with less urgent triage category scores and lower illness severity. Sepsis and respiratory admission diagnoses, and winter presentations were significantly more prevalent in this group.After adjustment for confounders, patients with an EDLOS > 4 hours had lower hospital mortality; 8% v 21% (p = 0.029; OR, 1.62), shorter ICU length of stay 2.2 v 2.4 days (p = 0.043), but a longer hospital length of stay 6.2 v 6.8 days (p = < 0.001). Conclusion: Almost two thirds of patients breached the NEAT of 4 hours. These patients were more likely to be older, female, admitted in winter with sepsis and respiratory diagnoses, and have lower illness severity and less urgent triage categories. NEAT breach was associated with reduced hospital mortality but an increased hospital length of stay.

The epidemiology of ketosis and low bicarbonate concentration in inpatients treated with sodium-glucose linked cotransporter inhibitors or dipeptidyl peptidase-4 inhibitors.

AIMS: To compare the level of ketones and bicarbonate in inpatients treated with sodium-glucose linked cotransporter 2 inhibitors (SGLT2i) and those treated with dipeptidyl peptidase-4 inhibitors (DPP4i). METHODS: We conducted an electronic medical records-based cohort study. We identified patients with type 2 diabetes, with ketone measurements available, who received SGLT2i (n = 82) or DPP4i (n = 308) during admission. We compared ketone levels between those who received SGLT2i or DPP4i using mixed ordinal logistic regression. The primary outcome was level of ketosis (<0.6, 0.6-1.5, 1.6-3.0, >3 mmol/L). Secondary outcomes included bicarbonate levels, hospital complications, ICU admission, and death. RESULTS: SGLT2i use was not associated with greater ketosis than DPP4i use, after adjusting for age, weight, Charlson Comorbidity Index, HbA1c, estimated glomerular filtration rate, principal diagnosis category, admission type and insulin administration (OR 4.52 95 % CI (0.33, 61.82)). After adjustment, there was no difference in complications (p = 0.14), ICU admissions (p = 0.64), mortality (p = 0.30), or bicarbonate levels (p = 0.97). CONCLUSION: Ketone levels were not greater in patients who received SGLT2i than those who received DPP4i. There were no differences in bicarbonate levels, complications, ICU admissions, or mortality, implying that, in inpatients, SGLT2i use is neither associated with ketosis nor adverse clinical outcomes.

Effect of a low versus intermediate tidal volume strategy on pulmonary complications in patients at risk of acute respiratory distress syndrome-a randomized clinical trial.

Introduction: There is no consensus on whether invasive ventilation should use low tidal volumes (VT) to prevent lung complications in patients at risk of acute respiratory distress syndrome (ARDS). The purpose of this study is to determine if a low VT strategy is more effective than an intermediate VT strategy in preventing pulmonary complications. Methods: A randomized clinical trial was conducted in invasively ventilated patients with a lung injury prediction score (LIPS) of >4 performed in the intensive care units of 10 hospitals in Spain and one in the United States of America (USA) from 3 November 2014 to 30 August 2016. Patients were randomized to invasive ventilation using low VT (≤ 6 mL/kg predicted body weight, PBW) (N = 50) or intermediate VT (> 8 mL/kg PBW) (N = 48). The primary endpoint was the development of ARDS during the first 7 days after the initiation of invasive ventilation. Secondary endpoints included the development of pneumonia and severe atelectases; the length of intensive care unit (ICU) and hospital stay; and ICU, hospital, 28- and 90-day mortality. Results: In total, 98 patients [67.3% male], with a median age of 65.5 years [interquartile range 55-73], were enrolled until the study was prematurely stopped because of slow recruitment and loss of equipoise caused by recent study reports. On day 7, five (11.9%) patients in the low VT group and four (9.1%) patients in the intermediate VT group had developed ARDS (risk ratio, 1.16 [95% CI, 0.62-2.17]; p = 0.735). The incidence of pneumonia and severe atelectasis was also not different between the two groups. The use of a low VT strategy did neither affect the length of ICU and hospital stay nor mortality rates. Conclusions: In patients at risk for ARDS, a low VT strategy did not result in a lower incidence of ARDS than an intermediate VT strategy.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02070666.

Delirium in ventilated patients receiving fentanyl and morphine for Analgosedation: Findings from the ANALGESIC trial.

PURPOSE: The differential effect of fentanyl vs. morphine analgosedation on the development of hospital inpatient delirium in patients receiving mechanical ventilation is unknown. We aimed to compare the incidence of coding for delirium and antipsychotic medication use in patients treated with fentanyl vs. morphine in the ANALGESIC trial. MATERIALS AND METHODS: We obtained data from a cluster randomized, cluster crossover trial of fentanyl vs. morphine for analgosedation on antipsychotic use and coding diagnosis of delirium and compared these outcomes according to treatment allocation. We assessed the relationship between opioid choice and dose, hospital inpatient delirium, and outcomes. RESULTS: Among 681 patients enrolled in the ANALGESIC trial, 160/344 (46.5%) in the fentanyl group vs. 132/337 (39.1%) in the morphine group (absolute difference 7.34% [95% CI -0.9 to 14.78]; RR: 1.19 [95%CI 1.00 to 1.41]; p = 0.053) developed hospital inpatient delirium. Antipsychotic use was linearly related to opioid dose. Antipsychotic use was not associated with increased mortality. CONCLUSIONS: Fentanyl is associated with a higher incidence of hospital inpatient delirium when used for analgosedation compared with morphine, and the dose of opioid is linearly related to the need for antipsychotic medication administration. The role of analgosedation in promoting delirium requires further investigation.

Low tidal volume ventilation for patients undergoing laparoscopic surgery: a secondary analysis of a randomised clinical trial.

BACKGROUND: We recently reported the results for a large randomized controlled trial of low tidal volume ventilation (LTVV) versus conventional tidal volume (CTVV) during major surgery when positive end expiratory pressure (PEEP) was equal between groups. We found no difference in postoperative pulmonary complications (PPCs) in patients who received LTVV. However, in the subgroup of patients undergoing laparoscopic surgery, LTVV was associated with a numerically lower rate of PPCs after surgery. We aimed to further assess the relationship between LTVV versus CTVV during laparoscopic surgery. METHODS: We conducted a post-hoc analysis of this pre-specified subgroup. All patients received volume-controlled ventilation with an applied PEEP of 5 cmH2O and either LTVV (6 mL/kg predicted body weight [PBW]) or CTVV (10 mL/kg PBW). The primary outcome was the incidence of a composite of PPCs within seven days. RESULTS: Three hundred twenty-eight patients (27.2%) underwent laparoscopic surgeries, with 158 (48.2%) randomised to LTVV. Fifty two of 157 patients (33.1%) assigned to LTVV and 72 of 169 (42.6%) assigned to conventional tidal volume developed PPCs within 7 days (unadjusted absolute difference, - 9.48 [95% CI, - 19.86 to 1.05]; p = 0.076). After adjusting for pre-specified confounders, the LTVV group had a lower incidence of the primary outcome than patients receiving CTVV (adjusted absolute difference, - 10.36 [95% CI, - 20.52 to - 0.20]; p = 0.046). CONCLUSION: In this post-hoc analysis of a large, randomised trial of LTVV we found that during laparoscopic surgeries, LTVV was associated with a significantly reduced PPCs compared to CTVV when PEEP was applied equally between both groups. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry no: 12614000790640.

Effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients (CONFIDENCE): protocol for a multicentre randomised controlled trial.

BACKGROUND: Fluid therapy is a common intervention in critically ill patients. It is increasingly recognised that deresuscitation is an essential part of fluid therapy and delayed deresuscitation is associated with longer invasive ventilation and length of intensive care unit (ICU) stay. However, optimal timing and rate of deresuscitation remain unclear. Lung ultrasound (LUS) may be used to identify fluid overload. We hypothesise that daily LUS-guided deresuscitation is superior to deresuscitation without LUS in critically ill patients expected to undergo invasive ventilation for more than 24 h in terms of ventilator free-days and being alive at day 28. METHODS: The "effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients" (CONFIDENCE) is a national, multicentre, open-label, randomised controlled trial (RCT) in adult critically ill patients that are expected to be invasively ventilated for at least 24 h. Patients with conditions that preclude a negative fluid balance or LUS examination are excluded. CONFIDENCE will operate in 10 ICUs in the Netherlands and enrol 1000 patients. After hemodynamic stabilisation, patients assigned to the intervention will receive daily LUS with fluid balance recommendations. Subjects in the control arm are deresuscitated at the physician's discretion without the use of LUS. The primary endpoint is the number of ventilator-free days and being alive at day 28. Secondary endpoints include the duration of invasive ventilation; 28-day mortality; 90-day mortality; ICU, in hospital and total length of stay; cumulative fluid balance on days 1-7 after randomisation and on days 1-7 after start of LUS examination; mean serum lactate on days 1-7; the incidence of reintubations, chest drain placement, atrial fibrillation, kidney injury (KDIGO stadium ≥ 2) and hypernatremia; the use of invasive hemodynamic monitoring, and chest-X-ray; and quality of life at day 28. DISCUSSION: The CONFIDENCE trial is the first RCT comparing the effect of LUS-guided deresuscitation to routine care in invasively ventilated ICU patients. If proven effective, LUS-guided deresuscitation could improve outcomes in some of the most vulnerable and resource-intensive patients in a manner that is non-invasive, easy to perform, and well-implementable. TRIAL REGISTRATION: ClinicalTrials.gov NCT05188092. Registered since January 12, 2022.

Early and prolonged continuous hypertonic saline infusion in patients with acute liver failure.

PURPOSE: To study patient characteristics, physiological changes, and outcomes associated with prolonged continuous hypertonic saline (HTS) infusion in acute liver failure (ALF). MATERIALS AND METHODS: Retrospective observational cohort study of adult patients with ALF. We collected clinical, biochemical, and physiological data six hourly for the first week, daily until day 30 or hospital discharge, and weekly, when documented, until day 180. RESULTS: Of 127 patients, 85 received continuous HTS. Compared with non-HTS patients they were more likely to receive continuous renal replacement therapy (CRRT) (p < 0.001) and mechanical ventilation (p < 0.001). Median HTS duration was 150 (Interquartile range (IQR): 84-168) hours, delivering a median 2244 (IQR: 979-4610) mmol sodium load. Median peak sodium concentration was 149 mmol/L vs 138 mmol/L in non-HTS patients (p < 0.001). The median rate of sodium increase with infusion was 0.1 mmol/L/h and median rate of decrease during weaning was 0.1 mmol/L every 6 h. Median lowest pH value was 7.29 vs. 7.35 in non-HTS patients. Survival of HTS patients was 72.9% overall and 72.2% without transplantation. CONCLUSIONS: In ALF patients, the prolonged administration of HTS infusion was not associated with severe hypernatremia or rapid shifts in serum sodium upon commencement, delivery, or weaning.

Nutrition care processes across hospitalisation in critically ill patients with COVID-19 in Australia: A multicentre prospective observational study.

BACKGROUND: The COVID-19 pandemic highlighted major challenges with usual nutrition care processes, leading to reports of malnutrition and nutrition-related issues in these patients. OBJECTIVE: The objective of this study was to describe nutrition-related service delivery practices across hospitalisation in critically ill patients with COVID-19 admitted to Australian intensive care units (ICUs) in the initial pandemic phase. METHODS: This was a multicentre (nine site) observational study in Australia, linked with a national registry of critically ill patients with COVID-19. Adult patients with COVID-19 who were discharged to an acute ward following ICU admission were included over a 12-month period. Data are presented as n (%), median (interquartile range [IQR]), and odds ratio (OR [95% confidence interval {CI}]). RESULTS: A total of 103 patients were included. Oral nutrition was the most common mode of nutrition (93 [93%]). In the ICU, there were 53 (52%) patients seen by a dietitian (median 4 [2-8] occasions) and malnutrition screening occurred in 51 (50%) patients most commonly with the malnutrition screening tool (50 [98%]). The odds of receiving a higher malnutrition screening tool score increased by 36% for every screening in the ICU (1st to 4th, OR: 1.39 [95% CI: 1.05-1.77] p = 0.018) (indicating increasing risk of malnutrition). On the ward, 51 (50.5%) patients were seen by a dietitian (median time to consult: 44 [22.5-75] hours post ICU discharge). The odds of dietetic consult increased by 39% every week while on the ward (OR: 1.39 [1.03-1.89], p = 0.034). Patients who received mechanical ventilation (MV) were more likely to receive dietetic input than those who never received MV. CONCLUSIONS: During the initial phases of the COVID-19 pandemic in Australia, approximately half of the patients included were seen by a dietitian. An increased number of malnutrition screens were associated with a higher risk score in the ICU and likelihood of dietetic consult increased if patients received MV and as length of ward stay increased.

Effect of mechanical power on mortality in invasively ventilated ICU patients without the acute respiratory distress syndrome: An analysis of three randomised clinical trials.

BACKGROUND: The mechanical power of ventilation (MP) has an association with outcome in invasively ventilated patients with the acute respiratory distress syndrome (ARDS). Whether a similar association exists in invasively ventilated patients without ARDS is less certain. OBJECTIVE: To investigate the association of mechanical power with mortality in ICU patients without ARDS. DESIGN: This was an individual patient data analysis that uses the data of three multicentre randomised trials. SETTING: This study was performed in academic and nonacademic ICUs in the Netherlands. PATIENTS: One thousand nine hundred and sixty-two invasively ventilated patients without ARDS were included in this analysis. The median [IQR] age was 67 [57 to 75] years, 706 (36%) were women. MAIN OUTCOME MEASURES: The primary outcome was the all-cause mortality at day 28. Secondary outcomes were the all-cause mortality at day 90, and length of stay in ICU and hospital. RESULTS: At day 28, 644 patients (33%) had died. Hazard ratios for mortality at day 28 were higher with an increasing MP, even when stratified for its individual components (driving pressure ( P  < 0.001), tidal volume ( P  < 0.001), respiratory rate ( P  < 0.001) and maximum airway pressure ( P  = 0.001). Similar associations of mechanical power (MP) were found with mortality at day 90, lengths of stay in ICU and hospital. Hazard ratios for mortality at day 28 were not significantly different if patients were stratified for MP, with increasing levels of each individual component. CONCLUSION: In ICU patients receiving invasive ventilation for reasons other than ARDS, MP had an independent association with mortality. This finding suggests that MP holds an added predictive value over its individual components, making MP an attractive measure to monitor and possibly target in these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02159196, ClinicalTrials.gov Identifier: NCT02153294, ClinicalTrials.gov Identifier: NCT03167580.