A systematic review and meta-analysis of the clinimetric properties of the core outcome measurement instruments for clinical effectiveness trials of nutritional and metabolic interventions in critical illness (CONCISE).

BACKGROUND: CONCISE is an internationally agreed minimum set of outcomes for use in nutritional and metabolic clinical research in critically ill adults. Clinicians and researchers need to be aware of the clinimetric properties of these instruments and understand any limitations to ensure valid and reliable research. This systematic review and meta-analysis were undertaken to evaluate the clinimetric properties of the measurement instruments identified in CONCISE. METHODS: Four electronic databases were searched from inception to December 2022 (MEDLINE via Ovid, EMBASE via Ovid, CINAHL via Healthcare Databases Advanced Search, CENTRAL via Cochrane). Studies were included if they examined at least one clinimetric property of a CONCISE measurement instrument or recognised variation in adults ≥ 18 years with critical illness or recovering from critical illness in any language. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for systematic reviews of Patient-Reported Outcome Measures was used. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used in line with COSMIN guidance. The COSMIN checklist was used to evaluate the risk of bias and the quality of clinimetric properties. Overall certainty of the evidence was rated using a modified Grading of Recommendations, Assessment, Development and Evaluation approach. Narrative synthesis was performed and where possible, meta-analysis was conducted. RESULTS: A total of 4316 studies were screened. Forty-seven were included in the review, reporting data for 12308 participants. The Short Form-36 Questionnaire (Physical Component Score and Physical Functioning), sit-to-stand test, 6-m walk test and Barthel Index had the strongest clinimetric properties and certainty of evidence. The Short Physical Performance Battery, Katz Index and handgrip strength had less favourable results. There was limited data for Lawson Instrumental Activities of Daily Living and the Global Leadership Initiative on Malnutrition criteria. The risk of bias ranged from inadequate to very good. The certainty of the evidence ranged from very low to high. CONCLUSIONS: Variable evidence exists to support the clinimetric properties of the CONCISE measurement instruments. We suggest using this review alongside CONCISE to guide outcome selection for future trials of nutrition and metabolic interventions in critical illness. TRIAL REGISTRATION: PROSPERO (CRD42023438187). Registered 21/06/2023.

Prevalence of hypophosphatemia in the ICU - Results of an international one-day point prevalence survey.

BACKGROUND & AIMS: Hypophosphatemia (HypoP) is associated with organ dysfunction and mortality. Despite its potential severe consequences, HypoP remains poorly characterized in terms of real prevalence and timing of onset. The primary objective was to determine the prevalence of HypoP defined as blood phosphate <0.8 and < 0.65 mmol/l on one particular day at international level. METHODS: One-day point prevalence survey conducted by the Section of Metabolism, Endocrinology and Nutrition (MEN) of the European Society of Intensive Care Medicine (ESICM) during week 11-2020. RESULTS: In total, 56 adult and 4 paediatric ICUs, from 22 countries participated: 41 ICUs were mixed medico surgical, the 19 others being cardiac, medical or surgical. Phosphate measurements were performed daily in 21 ICUs, and 1-3 times per week in 39 ICUs. On D-Day 909 patients (883 adults) were present and 668/883 (75.7%) had serum/plasma phosphate determined, revealing a HypoP in 103 (15.4%) patients aged 62 [18 to 85] years. Of those, 49 patients presented phosphate <0.65 mmol/l: cases of hypophosphatemia were detected at any time of patient's ICU stay. No HypoP was observed in children. A treatment protocol existed only in 41.1% of adult ICUs, independently of ICU type, or size. Only 41/98 of the HypoP patients (29/41 of patients with phosphate <0.65 mmol/l) were receiving phosphate. CONCLUSION: HypoP is present at least in 15.4% of ICU patients, and may occur at any time during the ICU stay. The absence of phosphate repletion protocols in 60% of participating ICUs is an unexpected finding, and confirms the necessity for the development of ICU phosphate protocols and guidelines. CLINICALTRIALS IDENTIFIER: NCT04201899.

[The Early Mobilization Network]. / Netzwerk Frühmobilisierung.

BACKGROUND: Since its foundation in 2011, the German Network for Early Mobilization of mechanically ventilated intensive care patients delivered, among others, more than 90 monthly newsletters, 14 research projects, and 3 national conferences. PURPOSE: The aim of this online survey was to evaluate whether members of the Network perceived a professional benefit for themselves and their intensive cate units (ICU). METHODS: An interprofessional online survey of 303 clinicians of the Network in German speaking countries in July 2019 was undertaken. The survey included questions about newsletters, personal benefits, perceived improvements on their workplaces, and future expectations. RESULTS: The response rate was 48% (n = 145), mainly nurses and physiotherapists. The majority perceived the newsletter as good. Members reported that the network extended their professional knowledge and improved the quality of the ICUs regarding early mobilization, delirium management, and interprofessional goals. Participants expressed a wish for more workshops, case reports, webinars, and other educational possibilities. CONCLUSIONS: Members of the network Early Mobilization perceived a personal and professional benefit. The network supported quality improvements projects in ICUs. The progress of the network may serve as an example for development of other professional networks.

Sugammadex and neostigmine dose-finding study for reversal of residual neuromuscular block at a train-of-four ratio of 0.2 (SUNDRO20)†,.

BACKGROUND: The aim of this dose-finding study was to evaluate the dose-response relationship of sugammadex and neostigmine to reverse a commonly observed level of incomplete recovery from rocuronium-induced neuromuscular block, that is, a train-of-four ratio (TOFR) ≥0.2. METHODS: Ninety-nine anaesthetized patients received rocuronium 0.6 mg kg(-1) i.v. for tracheal intubation and, if necessary, incremental doses of 0.1-0.2 mg kg(-1). Neuromuscular monitoring was performed by calibrated electromyography. Once the TOFR recovered to 0.2, patients were randomized to receive sugammadex (0.25, 0.5, 0.75, 1.0, or 1.25 mg kg(-1) i.v.), neostigmine (10, 25, 40, 55, or 70 µg kg(-1) i.v.), or saline (n=9 per group). Primary and secondary end points were the doses necessary to restore neuromuscular function to a TOFR≥0.9 with an upper limit of 5 and 10 min for 95% of patients, respectively. RESULTS: Neostigmine was not able to fulfil the end points. Based on the best-fitting model, the sugammadex dose estimation for recovery to a TOFR≥0.9 for 95% of patients within 5 and 10 min was 0.49 and 0.26 mg kg(-1), respectively. CONCLUSION: A residual neuromuscular block of a TOFR of 0.2 cannot be reversed reliably with neostigmine within 10 min. In the conditions studied, substantially lower doses of sugammadex than the approved dose of 2.0 mg kg(-1) may be sufficient to reverse residual rocuronium-induced neuromuscular block at a recovery of TOFR≥0.2. CLINICAL TRIAL REGISTRATION: NCT01006720.

Effects of single-shot and steady-state propofol anaesthesia on rocuronium dose-response relationship: a randomised trial.

BACKGROUND: Similar to volatile anaesthetics, propofol may influence neuromuscular transmission. We hypothesised that the administration of propofol influenced the potency of rocuronium depending on the duration of the administration. METHODS: After consent, patients scheduled for elective surgery randomly received rocuronium either after induction of anaesthesia with propofol (2 min of propofol, n = 36) or after 30 min of propofol infusion (30 min of propofol, n = 36). Remifentanil was given in both groups. Neuromuscular monitoring was performed by calibrated electromyography. The dose-response relationship of rocuronium was determined with a single-bolus technique (0.07, 0.1, 0.15, 0.2, 0.3 and 0.45 mg/kg rocuronium). The primary endpoints were the ED50 and ED95 of rocuronium after 2 and 30 min propofol. Data are presented as means with (95% confidence interval). The trial is registered with the Eudra-CT: 2009-012815-16. RESULTS: A total of 72 patients were included. Time to maximal neuromuscular blockade was significantly shorter in patients after 30 min of propofol [3.3 min (2.9-3.7)] compared with patients anaesthetised with 2 min of propofol [4.6 min (4.0-5.2)]. After 30 min of propofol, the slope of the dose-response curve was significantly steeper (30 min of propofol: 4.34 [3.62-5.05]; 2 min of propofol: [3.34 (2.72-3.96)], resulting in lower ED95 values of rocuronium (30 min of propofol: 0.287 mg/kg [0.221-0.368]; 2 min of propofol [0.391 mg/kg (0.296-0.520)]. The ED50 were not different between groups. CONCLUSION: The potency of rocuronium was significantly enhanced after propofol infusion for 30 min. Estimates of potency those are usually determined during steady-state anaesthesia might underestimate rocuronium requirements for endotracheal intubation at the time of induction.

Block of postjunctional muscle-type acetylcholine receptors in vivo causes train-of-four fade in mice.

BACKGROUND: Train-of-four (TOF) fade during nerve-mediated muscle contraction is postulated to be attributable to inhibition of prejunctional nicotinic α3ß2 acetylcholine receptors (nAChRs), while decrease of twitch tension is attributable to block of postjunctional muscle nAChRs. The validity of these presumptions was tested using specific prejunctional and postjunctional nAChR antagonists, testing the hypothesis that fade is not always a prejunctional phenomenon. METHODS: Pentobarbital anaesthetized mice had TOF fade measured after administration of: either 0.9% saline; the prejunctional α3ß2 nAChR antagonist, dihydro-ß-erythroidine (DHßE); the postjunctional nAChR antagonists, α-bungarotoxin (α-BTX) or α-conotoxin GI; and a combination of α-BTX and DHßE; or a combination of α-conotoxin GI and DHßE. RESULTS: Saline caused no neuromuscular changes. Administration of muscle nAChR antagonists, α-BTX or α-conotoxin GI caused significant decrease of twitch tension and TOF fade compared with baseline (P<0.01). DHßE alone caused no change of twitch tension or fade even after 90 min, but its coadministration with α-BTX or α-conotoxin GI significantly accelerated the onset of paralysis and degree of fade compared with α-BTX or α-conotoxin GI alone (P<0.01). CONCLUSIONS: Occupation of postjunctional nAChRs alone by α-BTX or α-conotoxin GI causes fade. As the prejunctional effects of DHßE on fade became manifest only when co-administered with α-BTX or α-conotoxin GI, specific inhibition of prejunctional nAChR alone is not necessary and sufficient to cause fade. Fade observed during repetitive nerve stimulation can be because of block of either postjunctional nAChRs alone, or block of prejunctional and postjunctional nAChRs together.

Postoperative impairment of motor function at train-of-four ratio ≥0.9 cannot be improved by sugammadex (1 mg kg-1).

BACKGROUND: A train-of-four ratio (TOFR) ≥0.9 measured by quantitative neuromuscular monitoring is accepted as an indication of sufficient neuromuscular recovery for extubation, even though many postsynaptic acetylcholine receptors may still be inhibited. We investigated whether antagonism with sugammadex after spontaneous recovery to TOFR≥0.9 further improves muscle function or subjective well-being. METHODS: Following recovery to TOFR≥0.9 and emergence from anaesthesia, 300 patients randomly received either sugammadex 1.0 mg kg(-1) or placebo. Fine motor function (Purdue Pegboard Test) and maximal voluntary grip strength were measured before and after surgery (before and after test drug administration). At discharge from the postanaesthesia care unit, well-being was assessed with numerical analogue scales and the Quality-of-Recovery Score 40 (QoR-40). RESULTS: Patients' fine motor function [6 (sd 4) vs 15 (3) pegs (30 s)(-1), P<0.05] and maximal voluntary grip strength (284 (126) vs 386 (125) N, P<0.05) were significantly lower after anaesthesia compared with the pre-anaesthesia baseline. After sugammadex or placebo, motor function was significantly improved in both groups but did not reach the preoperative level. There was no difference between groups at any time. Global well-being was unaffected (QoR-40: placebo, 174 vs 185; sugammadex, 175 vs 186, P>0.05). CONCLUSIONS: Antagonizing rocuronium at TOF≥0.9 with sugammadex 1.0 mg kg(-) (1) did not improve patients' motor function or well-being when compared with placebo. Our data support the view that TOFR≥0.9 measured by electromyography signifies sufficient recovery of neuromuscular function. CLINICAL TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT01101139).