Enteral nutrition management in critically ill adult patients and its relationship with intensive care unit-acquired muscle weakness: A national cohort study.

OBJECTIVE: To assess the incidence and determinants of ICU-acquired muscle weakness (ICUAW) in adult patients with enteral nutrition (EN) during the first 7 days in the ICU and mechanical ventilation for at least 48 hours. METHODS: A prospective, nationwide, multicentre cohort study in a national ICU network of 80 ICUs. ICU patients receiving invasive mechanical ventilation for at least 48 hours and EN the first 7 days of their ICU stay were included. The primary outcome was incidence of ICUAW. The secondary outcome was analysed, during days 3-7 of ICU stay, the relationship between demographic and clinical data to contribute to the onset of ICUAW, identify whether energy and protein intake can contribute independently to the onset of ICUAW and degree of compliance guidelines for EN. RESULTS: 319 patients were studied from 69 ICUs in our country. The incidence of ICUAW was 153/222 (68.9%; 95% CI [62.5%-74.7%]). Patients without ICUAW showed higher levels of active mobility (p = 0.018). The logistic regression analysis showed no effect on energy or protein intake on the onset of ICUAW. Overfeeding was observed on a significant proportion of patient-days, while more overfeeding (as per US guidelines) was found among patients with obesity than those without (42.9% vs 12.5%; p<0.001). Protein intake was deficient (as per US/European guidelines) during ICU days 3-7. CONCLUSIONS: The incidence of ICUAW was high in this patient cohort. Early mobility was associated with a lower incidence of ICUAW. Significant overfeeding and deficient protein intake were observed. However, energy and protein intake alone were insufficient to explain ICUAW onset. RELEVANCE TO CLINICAL PRACTICE: Low mobility, high incidence of ICUAW and low protein intake suggest the need to train, update and involve ICU professionals in nutritional care and the need for early mobilization of ICU patients.

Safety and immunogenicity of the protein-based PHH-IV compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.

Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine -either heterologous (PHH-1V group) or homologous (BNT162b2 group)- in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus [≥]65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections [≥]14 days after PHH-1V booster. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553. Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n=522) or BNT162b2 (n=260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p<0.0001), 1.31 (p=0.0007) and 0.86 (p=0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p<0.0001), 0.65 (p<0.0001) and 0.56 (p=0.003) for the Beta variant; 1.01 (p=0.92), 0.88 (p=0.11) and 0.52 (p=0.0003) for the Delta variant; and 0.59 (p=<0.0001), 0.66 (p<0.0001) and 0.57 (p=0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-{gamma} on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p=0.45), and none of the subjects developed severe COVID-19. Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and Delta SARS-CoV-2 variants, as well as the currently circulating Omicron BA.1. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. Funding: HIPRA SCIENTIFIC, S.L.U.

The impact of ABCDE bundle implementation on patient outcomes: A nationwide cohort study.

BACKGROUND: The ABCDE bundle is a set of evidence-based practices to systematically reduce the risks of sedation, delirium, and immobility in intensive care patients. Implementing the bundle improves clinical outcome. AIMS AND OBJECTIVES: To investigate the association between patient outcomes and compliance with bundle components ABC (analgosedation algorithms), D (delirium protocol), and E (early mobilization protocol). DESIGN: A Spanish multicentre cohort study of adult patients receiving invasive mechanical ventilation (IMV) for ≥48 h until extubation. METHODS: The primary outcome was pain level, cooperation to permit Medical Research Council Scale administration, patient days of delirium, and mobility. The secondary outcome was cumulative drug dosing by IMV days. Tertiary outcomes (ICU days, IMV days, bed rest days, ICU mortality, ICUAW) and independent variables (analgosedation, delirium, early mobilization protocols) were also studied. RESULTS: Data were collected from 605 patients in 80 ICUs and 5214 patient days with IMV. Two-thirds of the ICUs studied applied no protocols. Pain was not assessed on 83.6% of patient days. Patient cooperation made scale administration feasible on 20.7% of days. Delirium and immobility were found on 4.2% and 69.9% of days, respectively. Patients had shorter stays in ICUs with bundle protocols and fewer days of IMV in ICUs with delirium and mobilization bundle components (P = 0.006 and P = 0.03, respectively). Analgosedation protocols were associated with more opioid dosing (P = 0.02), and delirium and early mobilization protocols with more propofol (P = 0.001), dexmedetomidine (P = 0.001), and lower benzodiazepine dosing (P = 0.008). CONCLUSIONS: The implementation rate of ABCDE bundle components was very low in our Spanish setting, but when implemented, patients had a shorter ICU stay, more analgesia dosing, and lighter sedation. RELEVANCE TO CLINICAL PRACTICE: Applying some but not all the bundle components, there is increased analgesia and light sedation drug use, decreased benzodiazepines, and increased patient cooperation and mobility, resulting in a shorter ICU stay and fewer days of IMV.

Variables associated with mobility levels in critically ill patients: A cohort study.

BACKGROUND: Early mobilization in the intensive care unit (ICU) helps improve patients' functional status at discharge. However, many barriers hinder this practice. AIM AND OBJECTIVES: To identify mobility levels acquired by critically ill patients and their variables. DESIGN: A multi-centre cohort study was conducted in adult patients receiving invasive mechanical ventilation for at least 48 hours. METHODS: The primary outcome was level of mobility according to the ICU mobility scale. The secondary outcome was human resource availability and existence of ABCDEF bundle guidelines. A logistic regression was performed, based on days 3 to 5 of the ICU stay and significant association with active mobility. RESULTS: Six hundred and forty-two patients were included from 80 ICUs. Active moving in and out of bed was found on 9.9% of patient-days from day 8 of the ICU stay. Bed exercises, or passive transfers, and immobility were observed on 45.6% and 42.2% of patient-days, respectively. Patients achieving active mobility (189/642, 29.4%) were in ICUs with more physiotherapist hours. Active mobility was more likely with a 1:4 nurse-patient ratio (odds ratio [OR] 3.7 95% confidence interval [CI] [1.2-11.2]), high MRC sum-score (OR 1.05 95% CI [1.04-1.06]) and presence of delirium (OR 1.01 95% CI [1.00-1.02]). By contrast, active mobility was hindered by higher BMI (OR 0.92 95% CI [0.88-0.97]), a 1:3 nurse-patient ratio (OR 0.54 95% CI [0.32-0.93]), or a shift-dependent nurse-patient ratio (OR 0.27 95% CI [0.12-0.62]). CONCLUSIONS: Immobility and passive mobilization were prevalent. A high MRC sum-score and presence of delirium are protective factors of mobilization. A 1:4 nurse-patient ratio shows a stronger association with active mobility than a 1:3 ratio. RELEVANCE TO CLINICAL PRACTICE: Severity-criteria-based nurse-patient ratios hinder mobilization. Active mobilization may be enhanced by using nursing-intervention-based ratios, increasing physiotherapist hours, and achieving wider application of the ABCDEF bundle, resulting in more awake, cooperative patients.

Care and treatments related to intensive care unit-acquired muscle weakness: A cohort study.

BACKGROUND: Intensive care unit-acquired muscle weakness (ICUAW) has an incidence of 40-46%. Early mobilisation is known to be a protective factor. OBJECTIVE: The aim of the study was to identify the incidence of ICUAW in Spain and to evaluate variables likely to contribute to the development of ICUAW. METHODS: A 4-month, prospective observational multicentre cohort study was conducted on patients receiving invasive mechanical ventilation for at least 48 h. Data were collected from ICU day 3 until ICU discharge. The primary outcome was presence of ICUAW (diagnosed using the Medical Research Council [MRC] scale). The secondary outcome was nurse-patient ratio, physiotherapist availability, analgesia, sedation and delirium management, glycaemic control, and daily level of mobility during the ICU stay as per the ICU Mobility Scale. A logistic regression model was constructed based exclusively on days 3-5 of the ICU stay. RESULTS: The data of 642 patients were analysed from 80 ICUs, accounting for 35% of all ICUs in Spain. The incidence of ICUAW was 58% (275 of 474 patients; 95% confidence interval [CI] [53-62]). The predictors for ICUAW were older age (odds ratio [OR] = 1.01; 95% CI [1.00-1.03]) and more days with renal replacement therapy (OR = 1.01; 95% CI [1.00-1.02]). The protective factors for ICUAW were male gender (OR = 0.58; 95% CI [0.38-0.89]), higher Barthel Index (showing prehospital functional independence) (OR = 0.97; 95% CI [0.95-0.99]), more days of being awake and cooperative (defined by a feasible MRC assessment) (OR = 0.98; 95% CI [0.97-0.99]), presence of delirium (OR = 0.98; 95% CI [0.97-0.99]), and more days with active mobilisation (ICU Mobility Scale ≥ 4) (OR = 0.98; 95% CI [0.97-0.99]). CONCLUSIONS: The risk factors for ICUAW were functional dependence before admission, female gender, older age, and more days on renal replacement therapy. The protective factors for ICUAW were feasibility of MRC assessment, the presence of delirium, and being actively mobilised during the first 5 days in the ICU.

Intervenciones no farmacológicas para la promoción del sueño en la UCI / Non-pharmacological interventions for sleep promotion in the ICU

No disponible

Grado de implementación de las estrategias preventivas del síndrome post-UCI: estudio observacional multicéntrico en España / Degree of implementation of preventive strategies for post-ICU syndrome: Multi-centre, observational study in Spain

Objetivo: Evaluar el nivel de implementación de los protocolos asociados a la prevención de la debilidad muscular adquirida en la unidad de cuidados intensivos (UCI), así como la presencia del fisioterapeuta en distintas UCI de España. Método: Estudio descriptivo, transversal realizado en 86 UCI de adultos de España entre los meses de marzo a junio de 2017. Se excluyeron UCI neuroquirúrgicas y de grandes quemados. Se utilizó encuesta multirrespuesta que incluía preguntas sobre los protocolos de: control de glucemia, sedación, valoración del dolor, prevención del delirium, manejo del delirium y movilización precoz. La encuesta fue rellenada a través de un aplicativo protegido por usuario y contraseña. Análisis inferencial con t de Student o U de Mann-Whitney y de correlación con Pearson o Rho de Spearman. Resultados: El 89,5% de las UCI tenían protocolo de control de glucemia, con rango predominante de 110-140 mg/dl. El 74,4% evaluaban el nivel de sedación, si bien solo tenían protocolos de sedación el 36% de ellas. Con relación a la valoración del dolor se realizaba en el 73,7% de los pacientes comunicativos, mientras que en los no comunicativos solo era del 47,5%. Solo el 37,2% realizaban screening diario para detectar el delirium, y disponían de protocolos de prevención del delirium el 31,4% de las UCI, del manejo del delirium el 26,7% y de movilización precoz el 14% de las UCI. En el 34,9% de los casos se solicita interconsulta al servicio de rehabilitación. Conclusiones: La implementación de los diferentes protocolos asociados a la prevención de la debilidad muscular adquirida ha sido elevada en relación con los protocolos de control de glucemia, valoración del nivel de sedación y del dolor de pacientes comunicativos, mientras que baja en los de movilización precoz y screening y prevención del delirio. Asimismo, es poco frecuente la presencia del fisioterapeuta en la UCI

Aim: To evaluate the degree of implementation of protocols associated with the prevention of intensive-care-unit (ICU) acquired muscle weakness, and the presence of the physiotherapist in various ICU in Spain. Method: A descriptive, cross-sectional study performed in 86 adult ICU in Spain between March and June 2017. Neurosurgical and major burns ICU were excluded. A multiple-choice survey was used that included questions on protocols for glycaemia control, sedation, pain assessment, delirium prevention, delirium management and early mobilisation. The survey was completed using a user-protected application and password. The Student's t-test or Mann-Whitney U test and Pearson's correlation or Spearman's Rho test were used for the inferential analysis. Results: Eighty-nine point five percent of the ICU had a glycaemia control protocol, with a predominating range of 110-140 mg/dl. Seventy-four point four percent evaluated sedation levels, although only 36% had sedation protocols. Pain assessment was carried out on communicative patients in 73.7%, and on uncommunicative patients in only 47.5%. Only 37.2% performed daily screening to detect delirium and 31.4% of the ICU had delirium prevention protocols, 26.7% had delirium management protocols and 14% had protocols for early mobilisation. Thirty-four point nine percent requested cross consultation with the rehabilitation department. Conclusions: The implementation of the different protocols associated with the prevention of ICU-acquired muscle weakness was high in relation to glycaemia control protocols, sedation level and pain assessment in communicative patients, and was low for early mobilisation and delirium screening and prevention. Similarly, the physiotherapist was seldom present in the ICU

Degree of implementation of preventive strategies for post-ICU syndrome: Multi-centre, observational study in Spain. / Grado de implementación de las estrategias preventivas del síndrome post-UCI: estudio observacional multicéntrico en España.

AIM: To evaluate the degree of implementation of protocols associated with the prevention of intensive-care-unit (ICU) acquired muscle weakness, and the presence of the physiotherapist in various ICU in Spain. METHOD: A descriptive, cross-sectional study performed in 86 adult ICU in Spain between March and June 2017. Neurosurgical and major burns ICU were excluded. A multiple-choice survey was used that included questions on protocols for glycaemia control, sedation, pain assessment, delirium prevention, delirium management and early mobilisation. The survey was completed using a user-protected application and password. The Student's t-test or Mann-Whitney U test and Pearson's correlation or Spearman's Rho test were used for the inferential analysis. RESULTS: Eighty-nine point five percent of the ICU had a glycaemia control protocol, with a predominating range of 110-140mg/dl. Seventy-four point four percent evaluated sedation levels, although only 36% had sedation protocols. Pain assessment was carried out on communicative patients in 73.7%, and on uncommunicative patients in only 47.5%. Only 37.2% performed daily screening to detect delirium and 31.4% of the ICU had delirium prevention protocols, 26.7% had delirium management protocols and 14% had protocols for early mobilisation. Thirty-four point nine percent requested cross consultation with the rehabilitation department. CONCLUSIONS: The implementation of the different protocols associated with the prevention of ICU-acquired muscle weakness was high in relation to glycaemia control protocols, sedation level and pain assessment in communicative patients, and was low for early mobilisation and delirium screening and prevention. Similarly, the physiotherapist was seldom present in the ICU.