RESUMO
BACKGROUND: Increased protein provision might ameliorate muscle wasting and improve long-term outcomes in critically ill patients. The aim of the PRECISe trial was to assess whether higher enteral protein provision (ie, 2·0 g/kg per day) would improve health-related quality of life and functional outcomes in critically ill patients who were mechanically ventilated compared with standard enteral protein provision (ie, 1·3 g/kg per day). METHODS: The PRECISe trial was an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in five Dutch hospitals and five Belgian hospitals. Inclusion criteria were initiation of invasive mechanical ventilation within 24 h of intensive care unit (ICU) admission and an expected duration of invasive ventilation of 3 days or longer. Exclusion criteria were contraindications for enteral nutrition, moribund condition, BMI less than 18 kg/m2, kidney failure with a no dialysis code, or hepatic encephalopathy. Patients were randomly assigned to one of four randomisation labels, corresponding with two study groups (ie, standard or high protein; two labels per group) in a 1:1:1:1 ratio through an interactive web-response system. Randomisation was done via random permuted-block randomisation in varying block sizes of eight and 12, stratified by centre. Participants, care providers, investigators, outcome assessors, data analysts, and the independent data safety monitoring board were all blinded to group allocation. Patients received isocaloric enteral feeds that contained 1·3 kcal/mL and 0·06 g of protein/mL (ie, standard protein) or 1·3 kcal/mL and 0·10 g of protein/mL (ie, high protein). The study-nutrition intervention was limited to the time period during the patient's ICU stay in which they required enteral feeding, with a maximum of 90 days. The primary outcome was EuroQoL 5-Dimension 5-level (EQ-5D-5L) health utility score at 30 days, 90 days, and 180 days after randomisation, adjusted for baseline EQ-5D-5L health utility score. This trial was registered with ClinicalTrials.gov (NCT04633421) and is closed to new participants. FINDINGS: Between Nov 19, 2020, and April 14, 2023, 935 patients were randomly assigned. 335 (35·8%) of 935 patients were female and 600 (64·2%) were male. 465 (49·7%) of 935 were assigned to the standard protein group and 470 (50·3%) were assigned to the high protein group. 430 (92·5%) of 465 patients in the standard protein group and 419 (89·1%) of 470 patients in the high protein group were assessed for the primary outcome. The primary outcome, EQ-5D-5L health utility score during 180 days after randomisation (assessed at 30 days, 90 days, and 180 days), was lower in patients allocated to the high protein group than in those allocated to the standard protein group, with a mean difference of -0·05 (95% CI -0·10 to -0·01; p=0·031). Regarding safety outcomes, the probability of mortality during the entire follow-up was 0·38 (SE 0·02) in the standard protein group and 0·42 (0·02) in the high protein group (hazard ratio 1·14, 95% CI 0·92 to 1·40; p=0·22). There was a higher incidence of symptoms of gastrointestinal intolerance in patients in the high protein group (odds ratio 1·76, 95% CI 1·06 to 2·92; p=0·030). Incidence of other adverse events did not differ between groups. INTERPRETATION: High enteral protein provision compared with standard enteral protein provision resulted in worse health-related quality of life in critically ill patients and did not improve functional outcomes during 180 days after ICU admission. FUNDING: Netherlands Organisation for Healthcare Research and Development and Belgian Health Care Knowledge Centre.
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Estado Terminal , Proteínas Alimentares , Nutrição Enteral , Qualidade de Vida , Humanos , Masculino , Feminino , Estado Terminal/terapia , Bélgica , Método Duplo-Cego , Pessoa de Meia-Idade , Países Baixos , Nutrição Enteral/métodos , Idoso , Proteínas Alimentares/administração & dosagem , Recuperação de Função Fisiológica , Respiração Artificial , Unidades de Terapia IntensivaRESUMO
BACKGROUND: The PRECISe trial is a pragmatic, multicenter randomized controlled trial that evaluates the effect of high versus standard enteral protein provision on functional recovery in adult, mechanically ventilated critically ill patients. The current protocol presents the rationale and analysis plan for an evaluation of the primary and secondary outcomes under the Bayesian framework, with an emphasis on clinically important effect sizes. METHODS: This protocol was drafted in agreement with the ROBUST-statement, and is submitted for publication before database lock and primary data analysis. The primary outcome is health-related quality of life as measured by the EQ-5D-5L health utility score and is longitudinally assessed. Secondary outcomes comprise the 6-min walking test and handgrip strength over the entire follow-up period (longitudinal analyses), and 60-day mortality, duration of mechanical ventilation, and EQ-5D-5L health utility scores at 30, 90 and 180 days (cross-sectional). All analyses will primarily be performed under weakly informative priors. When available, informative priors elicited from contemporary literature will also be incorporated under alternative scenarios. In all other cases, objectively formulated skeptical and enthusiastic priors will be defined to assess the robustness of our results. Relevant identified subgroups were: patients with acute kidney injury, severe multi-organ failure and patients with or without sepsis. Results will be presented as absolute risk differences, mean differences, and odds ratios, with accompanying 95% credible intervals. Posterior probabilities will be estimated for clinically important benefit and harm. DISCUSSION: The proposed secondary, pre-planned Bayesian analysis of the PRECISe trial will provide additional information on the effects of high protein on functional and clinical outcomes in critically ill patients, such as probabilistic interpretation, probabilities of clinically important effect sizes, and the integration of prior evidence. As such, it will complement the interpretation of the primary outcome as well as several secondary and subgroup analyses.
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Estado Terminal , Qualidade de Vida , Adulto , Humanos , Teorema de Bayes , Estado Terminal/terapia , Força da Mão , Estudos Transversais , Cuidados Críticos/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: During Intensive Care Unit (ICU) admission, patients demonstrate up to 15% muscle loss per week, contributing to neuromuscular weakness, complicating recovery and delaying return to daily life. Biomarkers for muscle loss could aid in early detection of patients at risk and help guide resources to mitigate muscle loss, e.g. physical therapy and protein supplementation. AIMS: To explore serum biomarkers for muscle mass and muscle loss in ICU patients using a metabolomics approach. METHODS: Mechanically ventilated patients with an unplanned ICU admission between June and December 2021 were prospectively studied. The cross-sectional area of the rectus femoris muscle was assessed using ultrasound (RFcsa) and 188 serum metabolites were assessed using the Biocrates™ AbsoluteIDQ p180 kit for targeted metabolomics. Patients were eligible for analysis when a serum sample drawn within 5 days of ICU admission and at least 1 RFcsa were available. In patients with sequential RFcsa measurements, muscle loss was defined as the negative slope of the regression line fitted to the RFcsa measurements per patient in the first 10 days of ICU admission. Correlations between baseline metabolite concentrations and baseline muscle mass, as well as between baseline metabolite concentrations and muscle loss were assessed using Pearson's test for correlations. To correct for multiple testing, the Benjamini-Hochberg procedure was used. RESULTS: Seventeen patients were eligible for analysis. Mean age was 62 (SD ± 9) years and the cohort was predominantly male (76%). Four metabolites correlated with baseline muscle mass: creatinine (R = 0.5, p = 0.041), glycerophospholipid PC_ae_C30_0 (R = 0.5, p = 0.034) and two acylcarnitines: C14_2 (R = 0.5, p = 0.042) and C10_2 (R = 0.5, p = 0.049). For muscle loss, significant associations were found for histidine (R = -0.8, p = 0.002) and three glycerophospholipids; PC_aa_C40_2 (R = 0.7, p = 0.015), PC_ae_C40_1 (R = 0.6, p = 0.032) and PC_aa_C42_1 (R = 0.6, p = 0.037). After correction for multiple testing, no significant associations remained. CONCLUSIONS: This exploratory analysis found certain metabolites to be associated with muscle mass and muscle loss. Future research, specifically addressing these metabolites is necessary to confirm or refute an association with muscle loss and determine their role as potential muscle loss marker.
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Estado Terminal , Músculo Quadríceps , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Músculo Quadríceps/diagnóstico por imagem , Creatinina , Cuidados Críticos , MetabolômicaRESUMO
PURPOSE OF REVIEW: Gastrointestinal (GI) dysfunction is common among critically ill patients and is associated with poor outcomes. In particular, nutrient delivery can be impaired in patients with GI dysfunction and pose a significant challenge to clinicians in daily clinical practice. This review aims to summarize the impact of GI dysfunction on nutrition therapy during critical illness and provide an update on recent advances in nutritional strategies during gastrointestinal dysfunction. RECENT FINDINGS: Although prognostic gastrointestinal dysfunction scoring systems exist, a lack of clear, uniform definitions of GI dysfunction limits diagnosis and subsequent adequate treatment. Recent studies have further investigated separate components of GI dysfunction in ICU patients, including the role of altered GI motility, nutrient digestion and absorption and the metabolic consequences of gut dysfunction. Various strategies to improve nutrient delivery are discussed. However, the evidence supporting their routine use is sometimes lacking. SUMMARY: GI dysfunction frequently occurs during critical illness and negatively affects nutrition therapy. Strategies to improve nutrient delivery during GI dysfunction are available, though more research into the diagnosis and pathophysiology of GI dysfunction will likely further improve patient outcomes.
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Estado Terminal , Gastroenteropatias , Humanos , Estado Terminal/terapia , Gastroenteropatias/tratamento farmacológico , Apoio Nutricional , Motilidade GastrointestinalRESUMO
BACKGROUND: Critically ill patients are subject to severe skeletal muscle wasting during intensive care unit (ICU) stay, resulting in impaired short- and long-term functional outcomes and health-related quality of life. Increased protein provision may improve functional outcomes in ICU patients by attenuating skeletal muscle breakdown. Supporting evidence is limited however and results in great variety in recommended protein targets. METHODS: The PRECISe trial is an investigator-initiated, bi-national, multi-center, quadruple-blinded randomized controlled trial with a parallel group design. In 935 patients, we will compare provision of isocaloric enteral nutrition with either a standard or high protein content, providing 1.3 or 2.0 g of protein/kg/day, respectively, when fed on target. All unplanned ICU admissions with initiation of invasive mechanical ventilation within 24 h of admission and an expected stay on ventilator support of at least 3 days are eligible. The study is designed to assess the effect of the intervention on functional recovery at 1, 3, and 6 months following ICU admission, including health-related quality of life, measures of muscle strength, physical function, and mental health. The primary endpoint of the trial is health-related quality of life as measured by the Euro-QoL-5D-5-level questionnaire Health Utility Score. Overall between-group differences will be assessed over the three time points using linear mixed-effects models. DISCUSSION: The PRECISe trial will evaluate the effect of protein on functional recovery including both patient-centered and muscle-related outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04633421 . Registered on November 18, 2020. First patient in (FPI) on November 19, 2020. Expected last patient last visit (LPLV) in October 2023.
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Qualidade de Vida , Respiração Artificial , Humanos , Respiração Artificial/efeitos adversos , Cuidados Críticos/métodos , Tempo , Recuperação de Função Fisiológica , Unidades de Terapia Intensiva , Estado Terminal , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
PURPOSE OF REVIEW: In critically ill patients, optimal protein provision remains a challenge given the wide range in recommended protein delivery in international guidelines and the lack of robust, high quality evidence. As patients are confronted with poor functional outcomes after admission, often attributed to muscle wasting and persisting for multiple years, there is a pressing need for optimal nutritional strategies in the ICU, particularly including protein. This review will discuss the recent literature with regard to purpose, timing and mode of protein delivery. RECENT FINDINGS: Recent studies on the effect of dose and timing of protein on clinical and functional outcomes are largely observational in nature and the protein delivery considered as "high" still often only nears the lower end of current recommendations. The majority of trials observed no effect of protein supplementation on mortality, muscle strength or function, though some report attenuation of muscle volume loss, especially when combined with muscle activation. There is no strong evidence that ICU patients should receive supplementation with any specific amino acids. SUMMARY: Though adequate protein provision is likely important, it is difficult to come to a uniform conclusion regarding dosing and timing due to conflicting results in mostly observational studies as well as different cut-off values for high, moderate and low protein intake. This topic is currently subject to large clinical trials.
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Aminoácidos , Estado Terminal , Humanos , Estado Terminal/terapia , Proteínas , Força Muscular , Suplementos NutricionaisAssuntos
COVID-19/complicações , Cuidados Críticos , Pneumopatias/epidemiologia , Pneumopatias/virologia , Respiração Artificial , Idoso , COVID-19/mortalidade , COVID-19/terapia , Feminino , Humanos , Pneumopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Países Baixos , Alta do Paciente , Prevalência , Testes de Função Respiratória , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The majority of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are admitted to the Intensive Care Unit (ICU) for mechanical ventilation. The role of multi-organ failure during ICU admission as driver for outcome remains to be investigated yet. DESIGN AND SETTING: Prospective cohort of mechanically ventilated critically ill with SARS-CoV-2 infection. PARTICIPANTS AND METHODS: 94 participants of the MaastrICCht cohort (21% women) had a median length of stay of 16 days (maximum of 77). After division into survivors (n = 59) and non-survivors (n = 35), we analysed 1555 serial SOFA scores using linear mixed-effects models. RESULTS: Survivors improved one SOFA score point more per 5 days (95% CI: 4-8) than non-survivors. Adjustment for age, sex, and chronic lung, renal and liver disease, body-mass index, diabetes mellitus, cardiovascular risk factors, and Acute Physiology and Chronic Health Evaluation II score did not change this result. This association was stronger for women than men (P-interaction = 0.043). CONCLUSIONS: The decrease in SOFA score associated with survival suggests multi-organ failure involvement during mechanical ventilation in patients with SARS-CoV-2. Surviving women appeared to improve faster than surviving men. Serial SOFA scores may unravel an unfavourable trajectory and guide decisions in mechanically ventilated patients with SARS-CoV-2.
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COVID-19/complicações , Cuidados Críticos , Insuficiência de Múltiplos Órgãos/etiologia , Escores de Disfunção Orgânica , Respiração Artificial , Sobreviventes/estatística & dados numéricos , Idoso , COVID-19/fisiopatologia , Estudos de Coortes , Estado Terminal/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/fisiopatologia , Países Baixos/epidemiologia , Estudos ProspectivosRESUMO
INTRODUCTION: The course of the disease in SARS-CoV-2 infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort (MaastrICCht). We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with a SARS-CoV-2 infection. METHODS AND ANALYSIS: Mechanically ventilated patients admitted to the intensive care with a SARS-CoV-2 infection will be included. We will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, ECGs, echocardiography as well as other imaging modalities to assess heterogeneity of the course of a SARS-CoV-2 infection in critically ill patients. The MaastrICCht is also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national intensive care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence. The spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS-CoV-2 infection in mechanically ventilated patients. Our study design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of the MaastrICCht. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the medical ethics committee (Medisch Ethische Toetsingscommissie 2020-1565/3 00 523) of the Maastricht University Medical Centre+ (Maastricht UMC+), which will be performed based on the Declaration of Helsinki. During the pandemic, the board of directors of Maastricht UMC+ adopted a policy to inform patients and ask their consent to use the collected data and to store serum samples for COVID-19 research purposes. All study documentation will be stored securely for fifteen years after recruitment of the last patient. The results will be published in peer-reviewed academic journals, with a preference for open access journals, while particularly considering deposition of the manuscripts on a preprint server early. TRIAL REGISTRATION NUMBER: The Netherlands Trial Register (NL8613).