Critical Care Bulletin - Feb 2023

 

Toward nutrition improving outcome of critically ill patients: How to interpret recent feeding RCTs?

 

by Jan Gunst, Michael P. Casaer, Jean-Charles Preiser, Jean Reignier and Greet Van den Berghe 

 

Critical Care volume 27, Article number: 43 Published: 27 January 2023

Abstract

Although numerous observational studies associated underfeeding with poor outcome, recent randomized controlled trials (RCTs) have shown that early full nutritional support does not benefit critically ill patients and may induce dose-dependent harm. Some researchers have suggested that the absence of benefit in RCTs may be attributed to overrepresentation of patients deemed at low nutritional risk, or to a too low amino acid versus non-protein energy dose in the nutritional formula. However, these hypotheses have not been confirmed by strong evidence. RCTs have not revealed any subgroup benefiting from early full nutritional support, nor benefit from increased amino acid doses or from indirect calorimetry-based energy dosing targeted at 100% of energy expenditure. Mechanistic studies attributed the absence of benefit of early feeding to anabolic resistance and futile catabolism of extra provided amino acids, and to feeding-induced suppression of recovery-enhancing pathways such as autophagy and ketogenesis, which opened perspectives for fasting-mimicking diets and ketone supplementation. Yet, the presence or absence of an anabolic response to feeding cannot be predicted or monitored and likely differs over time and among patients. In the absence of such monitor, the value of indirect calorimetry seems obscure, especially in the acute phase of illness. Until now, large feeding RCTs have focused on interventions that were initiated in the first week of critical illness. There are no large RCTs that investigated the impact of different feeding strategies initiated after the acute phase and continued after discharge from the intensive care unit in patients recovering from critical illness.

 

An updated “norepinephrine equivalent” score in intensive care as a marker of shock severity

 

by Yuki Kotani, Annamaria Di Gioia, Giovanni Landoni, Alessandro Belletti and Ashish K. Khanna 

 

Critical Care volume 27, Article number: 29 Published: 20 January 2023

Abstract

Vasopressors and fluids are the cornerstones for the treatment of shock. The current international guidelines on shock recommend norepinephrine as the first-line vasopressor and vasopressin as the second-line vasopressor. In clinical practice, due to drug availability, local practice variations, special settings, and ongoing research, several alternative vasoconstrictors and adjuncts are used in the absence of precise equivalent doses. Norepinephrine equivalence (NEE) is frequently used in clinical trials to overcome this heterogeneity and describe vasopressor support in a standardized manner. NEE quantifies the total amount of vasopressors, considering the potency of each such agent, which typically includes catecholamines, derivatives, and vasopressin. Intensive care studies use NEE as an eligibility criterion and also an outcome measure. On the other hand, NEE has several pitfalls which clinicians should know, important the lack of conversion of novel vasopressors such as angiotensin II and also adjuncts such as methylene blue, including a lack of high-quality data to support the equation and validate its predictive performance in all types of critical care practice. This review describes the history of NEE and suggests an updated formula incorporating novel vasopressors and adjuncts.

 

Electric impedance tomography-guided PEEP titration reduces mechanical power in ARDS: a randomized crossover pilot trial

by Jose Victor Jimenez, Elizabeth Munroe, Andrew J. Weirauch, Kelly Fiorino, Christopher A. Culter, Kristine Nelson, Wassim W. Labaki, Philip J. Choi, Ivan Co, Theodore J. Standiford, Hallie C. Prescott and Robert C. Hyzy 

Critical Care volume 27, Article number: 21 Published: 17 January 2023

Background

In patients with acute respiratory distress syndrome undergoing mechanical ventilation, positive end-expiratory pressure (PEEP) can lead to recruitment or overdistension. Current strategies utilized for PEEP titration do not permit the distinction. Electric impedance tomography (EIT) detects and quantifies the presence of both collapse and overdistension. We investigated whether using EIT-guided PEEP titration leads to decreased mechanical power compared to high-PEEP/FiO2 tables.

Methods

A single-center, randomized crossover pilot trial comparing EIT-guided PEEP selection versus PEEP selection using the High-PEEP/FiO2 table in patients with moderate–severe acute respiratory distress syndrome. The primary outcome was the change in mechanical power after each PEEP selection strategy. Secondary outcomes included changes in the 4 × driving pressure + respiratory rate (4 ΔP, + RR index) index, driving pressure, plateau pressure, PaO2/FiO2 ratio, and static compliance.

Results

EIT was consistently associated with a decrease in mechanical power compared to PEEP/FiO2 tables (mean difference − 4.36 J/min, 95% CI − 6.7, − 1.95, p = 0.002) and led to lower values in the 4ΔP + RR index (− 11.42 J/min, 95% CI − 19.01, − 3.82, p = 0.007) mainly driven by a decrease in the elastic–dynamic power (− 1.61 J/min, − 2.99, − 0.22, p = 0.027). The elastic–static and resistive powers were unchanged. Similarly, EIT led to a statistically significant change in set PEEP (− 2 cmH2O, p = 0.046), driving pressure, (− 2.92 cmH2O, p = 0.003), peak pressure (− 6.25 cmH2O, p = 0.003), plateau pressure (− 4.53 cmH2O, p = 0.006), and static respiratory system compliance (+ 7.93 ml/cmH2O, p = 0.008).

Conclusions

In patients with moderate–severe acute respiratory distress syndrome, EIT-guided PEEP titration reduces mechanical power mainly through a reduction in elastic–dynamic power.

 

“THE MANTLE” bundle for minimizing cerebral hypoxia in severe traumatic brain injury

by Daniel Agustin Godoy, Francisco Murillo-Cabezas, Jose Ignacio Suarez, Rafael Badenes, Paolo Pelosi and Chiara Robba 

Critical Care volume 27, Article number: 13 Published: 12 January 2023

Abstract

To ensure neuronal survival after severe traumatic brain injury, oxygen supply is essential. Cerebral tissue oxygenation represents the balance between oxygen supply and consumption, largely reflecting the adequacy of cerebral perfusion. Multiple physiological parameters determine the oxygen delivered to the brain, including blood pressure, hemoglobin level, systemic oxygenation, microcirculation and many factors are involved in the delivery of oxygen to its final recipient, through the respiratory chain. Brain tissue hypoxia occurs when the supply of oxygen is not adequate or when for some reasons it cannot be used at the cellular level. The causes of hypoxia are variable and can be analyzed pathophysiologically following “the oxygen route.” The current trend is precision medicine, individualized and therapeutically directed to the pathophysiology of specific brain damage; however, this requires the availability of multimodal monitoring. For this purpose, we developed the acronym “THE MANTLE,” a bundle of therapeutical interventions, which covers and protects the brain, optimizing the components of the oxygen transport system from ambient air to the mitochondria.

 

Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial

 

by Tarek Sharshar, Raphaël Porcher, Pierre Asfar, Lamiae Grimaldi, Julien Jabot, Laurent Argaud, Christine Lebert, Pierre-Edouard Bollaert, Marie Line Harlay, Patrick Chillet, Eric Maury, Francois Santoli, Pascal Blanc, Romain Sonneville, Dinh Chuyen Vu, Benjamin Rohaut… 

 

Critical Care volume 27, Article number: 8 Published: 09 January 2023

Background

Generalised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20–40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE.

Methods

This was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90.

Results

A total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89–1.19); p = 0.58]. There were no between-group differences for secondary outcomes.

Conclusions

VPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15.

 

Association between early nutrition support and 28-day mortality in critically ill patients: the FRANS prospective nutrition cohort study

by Emmanuel Pardo, Thomas Lescot, Jean-Charles Preiser, Pablo Massanet, Antoine Pons, Samir Jaber, Vincent Fraipont, Eric Levesque, Carole Ichai, Laurent Petit, Fabienne Tamion, Garry Taverny, Priscilla Boizeau, Corinne Alberti, Jean-Michel Constantin and Marie-Pierre Bonnet 

Critical Care volume 27, Article number: 7 Published: 07 January 2023

Background

Current guidelines suggest the introduction of early nutrition support within the first 48 h of admission to the intensive care unit (ICU) for patients who cannot eat. In that context, we aimed to describe nutrition practices in the ICU and study the association between the introduction of early nutrition support (< 48 h) in the ICU and patient mortality at day 28 (D28) using data from a multicentre prospective cohort.

Methods

The ‘French-Speaking ICU Nutritional Survey’ (FRANS) study was conducted in 26 ICUs in France and Belgium over 3 months in 2015. Adult patients with a predicted ICU length of stay > 3 days were consecutively included and followed for 10 days. Their mortality was assessed at D28. We investigated the association between early nutrition (< 48 h) and mortality at D28 using univariate and multivariate propensity-score-weighted logistic regression analyses.

Results

During the study period, 1206 patients were included. Early nutrition support was administered to 718 patients (59.5%), with 504 patients receiving enteral nutrition and 214 parenteral nutrition. Early nutrition was more frequently prescribed in the presence of multiple organ failure and less frequently in overweight and obese patients. Early nutrition was significantly associated with D28 mortality in the univariate analysis (crude odds ratio (OR) 1.69, 95% confidence interval (CI) 1.23–2.34) and propensity-weighted multivariate analysis (adjusted OR (aOR) 1.05, 95% CI 1.00–1.10). In subgroup analyses, this association was stronger in patients ≤ 65 years and with SOFA scores ≤ 8. Compared with no early nutrition, a significant association was found of D28 mortality with early enteral (aOR 1.06, 95% CI 1.01–1.11) but not early parenteral nutrition (aOR 1.04, 95% CI 0.98–1.11).

Conclusions

In this prospective cohort study, early nutrition support in the ICU was significantly associated with increased mortality at D28, particularly in younger patients with less severe disease. Compared to no early nutrition, only early enteral nutrition appeared to be associated with increased mortality. Such findings are in contrast with current guidelines on the provision of early nutrition support in the ICU and may challenge our current practices, particularly concerning patients at low nutrition risk.

 

Epidemiology and outcomes of early-onset AKI in COVID-19-related ARDS in comparison with non-COVID-19-related ARDS: insights from two prospective global cohort studies

 

by Bairbre A. McNicholas, Emanuele Rezoagli, Andrew J. Simpkin, Sankalp Khanna, Jacky Y. Suen, Pauline Yeung, Daniel Brodie, Gianluigi Li Bassi, Tai Pham, Giacomo Bellani, John F. Fraser and John Laffey 

Critical Care volume 27, Article number: 3 Published: 05 January 2023

Background

Acute kidney injury (AKI) is a frequent and severe complication of both COVID-19-related acute respiratory distress syndrome (ARDS) and non-COVID-19-related ARDS. The COVID-19 Critical Care Consortium (CCCC) has generated a global data set on the demographics, management and outcomes of critically ill COVID-19 patients. The LUNG-SAFE study was an international prospective cohort study of patients with severe respiratory failure, including ARDS, which pre-dated the pandemic.

Methods

The incidence, demographic profile, management and outcomes of early AKI in patients undergoing invasive mechanical ventilation for COVID-19-related ARDS were described and compared with AKI in a non-COVID-19-related ARDS cohort.

Results

Of 18,964 patients in the CCCC data set, 1699 patients with COVID-19-related ARDS required invasive ventilation and had relevant outcome data. Of these, 110 (6.5%) had stage 1, 94 (5.5%) had stage 2, 151 (8.9%) had stage 3 AKI, while 1214 (79.1%) had no AKI within 48 h of initiating invasive mechanical ventilation. Patients developing AKI were older and more likely to have hypertension or chronic cardiac disease. There were geo-economic differences in the incidence of AKI, with lower incidence of stage 3 AKI in European high-income countries and a higher incidence in patients from middle-income countries. Both 28-day and 90-day mortality risk was increased for patients with stage 2 (HR 2.00, p < 0.001) and stage 3 AKI (HR 1.95, p < 0.001). Compared to non-COVID-19 ARDS, the incidence of shock was reduced with lower cardiovascular SOFA score across all patient groups, while hospital mortality was worse in all groups [no AKI (30 vs 50%), Stage 1 (38 vs 58%), Stage 2 (56 vs 74%), and Stage 3 (52 vs 72%), p < 0.001]. The time profile of onset of AKI also differed, with 56% of all AKI occurring in the first 48 h in patients with COVID-19 ARDS compared to 89% in the non-COVID-19 ARDS population.

Conclusion

AKI is a common and serious complication of COVID-19, with a high mortality rate, which differs by geo-economic location. Important differences exist in the profile of AKI in COVID-19 versus non-COVID-19 ARDS in terms of their haemodynamic profile, time of onset and clinical outcomes.

 

Association Between Length of Storage of Transfused Packed RBC Units and Outcome of Surgical Critically Ill Adults: A Subgroup Analysis of the Age of Blood Evaluation Randomized Trial

 

by Lehr, Anab Rebecca; Hébert, Paul; Fergusson, Dean; Sabri, Elham; Lacroix, Jacques 

 

Critical Care Medicine: December 26, 2022. 

 

Objectives: The Age of Blood Evaluation (ABLE) study reported no clinical benefit in fresher compared with standard delivery RBC units (length of storage: 6.9 ± 4.1 vs 22.0 ± 8.4 d, respectively). Perioperative patients are often anemic, at risk of blood loss, and more exposed to RBC transfusions. We address the question whether fresh RBC units are safer than standard delivery RBC units in perioperative ICU patients.

Design: Subgroup analysis of surgical nontrauma adults enrolled in the ABLE randomized controlled trial.

Setting: ICUs.

Patients: Three hundred twenty surgical patients among the 2,510 ICU adults recruited in the ABLE study who had a request for a first RBC transfusion in the first week in ICU stay and an anticipated length of mechanical ventilation greater than or equal to 48 hours. We included perioperative patients but excluded elective cardiac surgery and trauma.

Interventions: Surgical participants were allocated to receive either RBC units stored less than or equal to 7 days or standard issue RBC.

MEASUREMENTS AND MAIN RESULTS: 

The primary outcome was 90-day all-cause mortality.

One hundred seventy-two perioperative patients were allocated to the fresh and 148 to the standard group. Baseline data were similar. The length of storage was 7.2 ± 6.4 in fresh and 20.6 ± 8.4 days in standard group (p < 0.0001). The 90-day mortality was 29.7% and 28.4%, respectively (absolute risk difference: 0.01; 95% CI –0.09 to 0.11; p = 0.803). No significant differences were observed for all secondary outcomes, including 6-month mortality, even after adjustment for age, country, and Acute Physiology and Chronic Health Evaluation score.

Conclusions: There was no evidence that fresh red cells improved outcomes as compared to standard issue red cells in critically ill surgical patients, consistent with other patients enrolled in the ABLE trial.

 

Association Between Socioeconomic Status and Outcomes in Critical Care: A Systematic Review and Meta-Analysis

 

by McHenry, Ryan D.; Moultrie, Christopher E. J.; Quasim, Tara; Mackay, Daniel F.; Pell, Jill P.

 

Critical Care Medicine, December 26, 2022.

 

Objectives: 

Socioeconomic status is well established as a key determinant of inequalities in health outcomes. Existing literature examining the impact of socioeconomic status on outcomes in critical care has produced inconsistent findings. Our objective was to synthesize the available evidence on the association between socioeconomic status and outcomes in critical care.

Data Sources: 

A systematic search of CINAHL, Ovid MEDLINE, and EMBASE was undertaken on September 13, 2022.

Study Selection: 

Observational cohort studies of adults assessing the association between socioeconomic status and critical care outcomes including mortality, length of stay, and functional outcomes were included. Two independent reviewers assessed titles, abstracts, and full texts against eligibility and quality criteria.

Data Extraction: 

Details of study methodology, population, exposure measures, and outcomes were extracted.

Data Synthesis: 

Thirty-eight studies met eligibility criteria for systematic review. Twenty-three studies reporting mortality to less than or equal to 30 days following critical care admission, and eight reporting length of stay, were included in meta-analysis. Random-effects pooled analysis showed that lower socioeconomic status was associated with higher mortality at less than or equal to 30 days following critical care admission, with pooled odds ratio of 1.13 (95% CIs, 1.05–1.22). Meta-analysis of ICU length of stay demonstrated no significant difference between socioeconomic groups. Socioeconomic status may also be associated with functional status and discharge destination following ICU admission.

Conclusions: 

Lower socioeconomic status was associated with higher mortality following admission to critical care.

 

The rate and assessment of muscle wasting during critical illness: a systematic review and meta-analysis

 

by Brigitta Fazzini, Tobias Märkl, Christos Costas, Manfred Blobner, Stefan J. Schaller, John Prowle, Zudin Puthucheary and Henning Wackerhage 

 

Critical Care volume 27, Article number: 2 Published: 03 January 2023

Background

Patients with critical illness can lose more than 15% of muscle mass in one week, and this can have long-term detrimental effects. However, there is currently no synthesis of the data of intensive care unit (ICU) muscle wasting studies, so the true mean rate of muscle loss across all studies is unknown. The aim of this project was therefore to systematically synthetise data on the rate of muscle loss and to identify the methods used to measure muscle size and to synthetise data on the prevalence of ICU-acquired weakness in critically ill patients.

Methods

We conducted a systematic literature search of MEDLINE, PubMed, AMED, BNI, CINAHL, and EMCARE until January 2022 (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD420222989540. We included studies with at least 20 adult critically ill patients where the investigators measured a muscle mass-related variable at two time points during the ICU stay. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and assessed the study quality using the Newcastle–Ottawa Scale.

Results

Fifty-two studies that included 3251 patients fulfilled the selection criteria. These studies investigated the rate of muscle wasting in 1773 (55%) patients and assessed ICU-acquired muscle weakness in 1478 (45%) patients. The methods used to assess muscle mass were ultrasound in 85% (n = 28/33) of the studies and computed tomography in the rest 15% (n = 5/33). During the first week of critical illness, patients lost every day −1.75% (95% CI −2.05, −1.45) of their rectus femoris thickness or −2.10% (95% CI −3.17, −1.02) of rectus femoris cross-sectional area. The overall prevalence of ICU-acquired weakness was 48% (95% CI 39%, 56%).

Conclusion

On average, critically ill patients lose nearly 2% of skeletal muscle per day during the first week of ICU admission.

 

Clustering of critically ill patients using an individualized learning approach enables dose optimization of mobilization in the ICU

 

by Kristina E. Fuest, Bernhard Ulm, Nils Daum, Maximilian Lindholz, Marco Lorenz, Kilian Blobner, Nadine Langer, Carol Hodgson, Margaret Herridge, Manfred Blobner and Stefan J. Schaller 

 

Critical Care volume 27, Article number: 1 Published: 03 January 2023

 

Background

While early mobilization is commonly implemented in intensive care unit treatment guidelines to improve functional outcome, the characterization of the optimal individual dosage (frequency, level or duration) remains unclear. The aim of this study was to demonstrate that artificial intelligence-based clustering of a large ICU cohort can provide individualized mobilization recommendations that have a positive impact on the likelihood of being discharged home.

Methods

This study is an analysis of a prospective observational database of two interdisciplinary intensive care units in Munich, Germany. Dosage of mobilization is determined by sessions per day, mean duration, early mobilization as well as average and maximum level achieved. A k-means cluster analysis was conducted including collected parameters at ICU admission to generate clinically definable clusters.

Results

Between April 2017 and May 2019, 948 patients were included. Four different clusters were identified, comprising “Young Trauma,” “Severely ill & Frail,” “Old non-frail” and “Middle-aged” patients. Early mobilization (< 72 h) was the most important factor to be discharged home in “Young Trauma” patients (ORadj 10.0 [2.8 to 44.0], p < 0.001). In the cluster of “Middle-aged” patients, the likelihood to be discharged home increased with each mobilization level, to a maximum 24-fold increased likelihood for ambulating (ORadj 24.0 [7.4 to 86.1], p < 0.001). The likelihood increased significantly when standing or ambulating was achieved in the older, non-frail cluster (ORadj 4.7 [1.2 to 23.2], p = 0.035 and ORadj 8.1 [1.8 to 45.8], p = 0.010).

Conclusions

An artificial intelligence-based learning approach was able to divide a heterogeneous critical care cohort into four clusters, which differed significantly in their clinical characteristics and in their mobilization parameters. Depending on the cluster, different mobilization strategies supported the likelihood of being discharged home enabling an individualized and resource-optimized mobilization approach.

 

Association between acute disease severity and one-year quality of life among post-hospitalisation COVID-19 patients: Coalition VII prospective cohort study

Intensive Care Medicine Published: 03 January 2023

Purpose

To assess the association between acute disease severity and 1-year quality of life in patients discharged after hospitalisation due to coronavirus disease 2019 (COVID-19).

Methods

We conducted a prospective cohort study nested in 5 randomised clinical trials between March 2020 and March 2022 at 84 sites in Brazil. Adult post-hospitalisation COVID-19 patients were followed for 1 year. The primary outcome was the utility score of EuroQol five-dimension three-level (EQ-5D-3L). Secondary outcomes included all-cause mortality, major cardiovascular events, and new disabilities in instrumental activities of daily living. Adjusted generalised estimating equations were used to assess the association between outcomes and acute disease severity according to the highest level on a modified ordinal scale during hospital stay (2: no oxygen therapy; 3: oxygen by mask or nasal prongs; 4: high-flow nasal cannula oxygen therapy or non-invasive ventilation; 5: mechanical ventilation).

Results

1508 COVID-19 survivors were enrolled. Primary outcome data were available for 1156 participants. At 1 year, compared with severity score 2, severity score 5 was associated with lower EQ-5D-3L utility scores (0.7 vs 0.84; adjusted difference, − 0.1 [95% CI − 0.15 to − 0.06]); and worse results for all-cause mortality (7.9% vs 1.2%; adjusted difference, 7.1% [95% CI 2.5%–11.8%]), major cardiovascular events (5.6% vs 2.3%; adjusted difference, 2.6% [95% CI 0.6%–4.6%]), and new disabilities (40.4% vs 23.5%; adjusted difference, 15.5% [95% CI 8.5%–22.5]). Severity scores 3 and 4 did not differ consistently from score 2.

Conclusions

COVID-19 patients who needed mechanical ventilation during hospitalisation have lower 1-year quality of life than COVID-19 patients who did not need mechanical ventilation during hospitalisation.