Succinylcholine versus rocuronium for rapid sequence intubation in intensive care: a prospective, randomized controlled trial

Succinylcholine and rocuronium are widely used to facilitate rapid sequence induction (RSI) intubation in intensive care. Concerns relate to the side effects of succinylcholine and to slower onset and inferior intubation conditions associated with rocuronium. So far, succinylcholine and rocuronium have not been compared in an adequately powered randomized trial in intensive care. Accordingly, the aim of the present study was to compare the incidence of hypoxemia after rocuronium or succinylcholine in critically ill patients requiring an emergent RSI

A bedside swallowing screen for the identification of post-extubation dysphagia on the intensive care unit – validation of the Gugging Swallowing Screen (GUSS)—ICU

Purpose Screening for dysphagia at the intensive care unit (ICU) soon after extubation can prevent aspiration, pneumonia, lower mortality, and shorten re‑feeding interval. This study aimed to modify the Gugging Swallowing Screen (GUSS), which was developed for acute stroke patients, and to validate it for extubated patients in the ICU. Methods In this prospective study, forty‑five patients who had been intubated for at least 24 h were recruited consecutively at the earliest 24 h after extubation. The modified GUSS‑ICU was performed twice by two speech and language therapists independently. Concurrently, gold standard the flexible endoscopic evaluation of swallowing (FEES) was performed by an otorhinolaryngologist. Measurements were conducted within a three‑hour period; all testers were blinded to each other’s results. Results According to FEES, 36 of 45 (80%) participants were diagnosed with dysphagia; 13 of those were severe, 12 moderate, and 11 mild. Compared to FEES, the GUSS‑ICU predicted dysphagia well (area under the curve for the initial rater pair: 0.923, 95% CI 0.832–1.000 and 0.923, 95% CI 0.836 ‑1.000 for the second rater pair). The sensitivity was 91.7% (95% CI 77.5–98.3%) and 94.4% (95% CI 81.3–99.3%); the specificity was 88.9% (51.8–99.7%) and 66.7% (29.9–92.5%); the positive predictive values were 97.1% (83.8–99.5%) and 91.9% (81.7–96.6%), and the negative predictive values were 72.7% (46.8–89%) and 75% (41.9–92.6%) for the first and second rater pairs, respectively. Dysphagia severity classification according to FEES and GUSS‑ICU correlated strongly (Spearman’s rho: 0.61 for rater 1 and 0.60 for rater 2, p < 0.001). Agreement by all testers was good (Krippendorffs Alpha: 0.73). The interrater reliability showed good agreement (Cohen`s Kappa: 0.84, p < 0.001). Conclusion The GUSS‑ICU is a simple, reliable, and valid multi‑consistency bedside swallowing screen to identify post‑extubation dysphagia at the ICU

A TNF Receptor 2 Selective Agonist Rescues Human Neurons from Oxidative Stress-Induced Cell Death

Tumor necrosis factor (TNF) plays a dual role in neurodegenerative diseases. Whereas TNF receptor (TNFR) 1 is predominantly associated with neurodegeneration, TNFR2 is involved in tissue regeneration and neuroprotection. Accordingly, the availability of TNFR2-selective agonists could allow the development of new therapeutic treatments of neurodegenerative diseases. We constructed a soluble, human TNFR2 agonist (TNC-scTNFR2) by genetic fusion of the trimerization domain of tenascin C to a TNFR2-selective single-chain TNF molecule, which is comprised of three TNF domains connected by short peptide linkers. TNC-scTNFR2 specifically activated TNFR2 and possessed membrane-TNF mimetic activity, resulting in TNFR2 signaling complex formation and activation of downstream signaling pathways. Protection from neurodegeneration was assessed using the human dopaminergic neuronal cell line LUHMES. First we show that TNC-scTNFR2 interfered with cell death pathways subsequent to H2O2 exposure. Protection from cell death was dependent on TNFR2 activation of the PI3K-PKB/Akt pathway, evident from restoration of H2O2 sensitivity in the presence of PI3K inhibitor LY294002. Second, in an in vitro model of Parkinson disease, TNC-scTNFR2 rescues neurons after induction of cell death by 6-OHDA. Since TNFR2 is not only promoting anti-apoptotic responses but also plays an important role in tissue regeneration, activation of TNFR2 signaling by TNC-scTNFR2 appears a promising strategy to ameliorate neurodegenerative processes

Incidence, risk factors, and outcome of aspiration pneumonitis in ICU overdose patients

Objective: To assess the incidence and outcome of clinically significant aspiration pneumonitis in intensive care unit (ICU) overdose patients and to identify its predisposing factors. Design: Retrospective cohort study. Setting: Medical ICU of an academic tertiary care hospital. Patients: Atotal of 273 consecutive overdose admissions. Measurements and results: Clinically significant aspiration pneumonitis was defined as the occurrence of respiratory dysfunction in apatient with alocalised infiltrate on chest X-ray within 72 h of admission. In our cohort we identified 47 patients (17%) with aspiration pneumonitis. Importantly, aspiration pneumonitis was associated with ahigher incidence of cardiac arrest (6.4 vs 0.9%; p = 0.037) and an increased duration of both ICU stay and overall hospital stay [respectively: median 1 (interquartile range 1-3) vs 1 (1-2), p = 0.025; and median 2 (1-7) vs 1 (1-3), p < 0.001]. In multivariate logistic regression analysis, Glasgow Coma Scale (GCS) score [odds ratio (OR) for each point of GCS 0.8; 95% confidence interval (CI) 0.7-0.9; p = 0.001], ingestion of opiates (OR 4.5; 95% CI 1.7-11.6; p = 0.002), and white blood cell count (WBC) (OR for each increase in WBC of 109/l 1.05; 95% CI 1.0-1.19; p = 0.049) were identified as independent risk factors. Conclusions: Clinically relevant aspiration pneumonitis is afrequent complication in overdose patients admitted to the ICU. Moreover, aspiration pneumonitis is associated with ahigher incidence of cardiac arrest and increased ICU and total in-hospital sta

Implementation of a multiprofessional, multicomponent delirium management guideline in two intensive care units, and its effect on patient outcomes and nurse workload: a pre-post design retrospective cohort study.

AIM OF THE STUDY Delirium is a frequent intensive care unit (ICU) complication, affecting 26% to 80% of ICU patients, often with serious consequences. This study aimed to evaluate the effectiveness, costs and benefits of following a standardised multiprofessional, multicomponent delirium guideline on eight outcomes: delirium prevalence and duration, lengths of stay in ICU and hospital, in-hospital mortality, duration of mechanical ventilation, and cost and nursing hours per case. It also aimed to explore the associations of delirium with length of ICU stay, length of hospital stay and duration of mechanical ventilation. METHODS This retrospective cohort study used a pre-post design. ICU patients in an historical control group (n = 1608) who received standard ICU care were compared with a postintervention group (n = 1684) who received standardised delirium management &ndash; delirium risk identification, preventive measures, screening and treatment &ndash; with regard to eight outcomes. The delirium management guideline was developed and implemented in 2012 by a group of experts from the study hospital. As appropriate, descriptive statistics and multivariate, multilevel models were used to compare the two groups and to explore the association between delirium occurrence and the selected outcomes. RESULTS Twelve percent of the 1608 historical controls and 20% of the 1684 postintervention patients were diagnosed with delirium according to the ICD-10 delirium diagnosis codes. Patients being treated for heart disease, and those with septic shock, ARDS, renal insufficiency (acute or chronic), older age and higher numbers of comorbidities were significantly more likely to develop delirium during their stay. Multivariate models comparing the historical controls with the post intervention group indicated significant differences in delirium period prevalence (odds ratio 1.68, 95% confidence interval [CI] 1.38&ndash;2.06; p &lt;0.001), length of stay in the ICU (time ratio [TR] 0.94, CI 0.89&ndash;1.00; p = 0.048), cost per case (median difference 3.83, CI 0.54&ndash;7.11; p = 0.023) and duration of mechanical ventilation (TR 0.84, CI 0.77&ndash;0.92; p &lt;0.001). The observed differences in the other four outcomes &ndash; in-hospital mortality, delirium duration, length of stay in the hospital, and nursing hours per case &ndash; were not significant. Delirium was a significant predictor for prolonged duration of mechanical ventilation and for both ICU and hospital stay. CONCLUSION Standardised delirium management, specifically delirium screening, supports timely detection of delirium in ICU patients. Increased awareness of delirium after the implementation of standardised multiprofessional, multicomponent management leads to increased therapeutic attention, a prolongation of ICU stay and increased costs, but with no influence on mortality

Protocolised early de-resuscitation in septic shock (REDUCE): protocol for a randomised controlled multicentre feasibility trial.

BACKGROUND Fluid overload is associated with excess mortality in septic shock. Current approaches to reduce fluid overload include restrictive administration of fluid or active removal of accumulated fluid. However, evidence on active fluid removal is scarce. The aim of this study is to assess the efficacy and feasibility of an early de-resuscitation protocol in patients with septic shock. METHODS All patients admitted to the intensive care unit (ICU) with a septic shock are screened, and eligible patients will be randomised in a 1:1 ratio to intervention or standard of care. INTERVENTION Fluid management will be performed according to the REDUCE protocol, where resuscitation fluid will be restricted to patients showing signs of poor tissue perfusion. After the lactate has peaked, the patient is deemed stable and assessed for active de-resuscitation (signs of fluid overload). The primary objective of this study is the proportion of patients with a negative cumulative fluid balance at day 3 after ICU. Secondary objectives are cumulative fluid balances throughout the ICU stay, number of patients with fluid overload, feasibility and safety outcomes and patient-centred outcomes. The primary outcome will be assessed by a logistic regression model adjusting for the stratification variables (trial site and chronic renal failure) in the intention-to-treat population. ETHICS AND DISSEMINATION The study was approved by the respective ethical committees (No 2020-02197). The results of the REDUCE trial will be published in an international peer-reviewed medical journal regardless of the results. TRIAL REGISTRATION NUMBER ClinicalTrials.gov, NCT04931485

Cerebral perfusion in sepsis-associated delirium

INTRODUCTION: The pathophysiology of sepsis-associated delirium is not completely understood and the data on cerebral perfusion in sepsis are conflicting. We tested the hypothesis that cerebral perfusion and selected serum markers of inflammation and delirium differ in septic patients with and without sepsis-associated delirium. METHODS: We investigated 23 adult patients with sepsis, severe sepsis, or septic shock with an extracranial focus of infection and no history of intracranial pathology. Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit. Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit. Mean arterial pressure (MAP), blood flow velocity (FV) in the middle cerebral artery using transcranial Doppler, and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour. An index of cerebrovascular autoregulation was calculated from MAP and FV data. C-reactive protein (CRP), interleukin-6 (IL-6), S-100beta, and cortisol were measured during each data acquisition. RESULTS: Data from 16 patients, of whom 12 had sepsis-associated delirium, were analysed. There were no significant correlations or associations between MAP, cerebral blood FV, or tissue oxygenation and sepsis-associated delirium. However, we found a significant association between sepsis-associated delirium and disturbed autoregulation (P = 0.015). IL-6 did not differ between patients with and without sepsis-associated delirium, but we found a significant association between elevated CRP (P = 0.008), S-100beta (P = 0.029), and cortisol (P = 0.011) and sepsis-associated delirium. Elevated CRP was significantly correlated with disturbed autoregulation (Spearman rho = 0.62, P = 0.010). CONCLUSION: In this small group of patients, cerebral perfusion assessed with transcranial Doppler and near-infrared spectroscopy did not differ between patients with and without sepsis-associated delirium. However, the state of autoregulation differed between the two groups. This may be due to inflammation impeding cerebrovascular endothelial function. Further investigations defining the role of S-100beta and cortisol in the diagnosis of sepsis-associated delirium are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00410111

Prolonged administration of beta-lactam antibiotics - a comprehensive review and critical appraisal

Prolonged infusion of β-lactam antibiotics as either extended (over at least 2 hours) or continuous infusion is increasingly applied in intensive care units around the world in an attempt to optimise treatment with this most commonly used class of antibiotics, whose effectiveness is challenged by increasing resistance rates. The pharmacokinetics of β-lactam antibiotics in critically ill patients is profoundly altered secondary to an increased volume of distribution and the presence of altered renal function, including augmented renal clearance. This may lead to a significant decrease in plasma concentrations of β-lactam antibiotics. As a consequence, low pharmacokinetic/pharmacodynamic (PK/PD) target attainment, which is described as the percentage of time that the free drug concentration is maintained above the minimal inhibitory concentration (MIC) of the causative organism (fT>MIC), has been documented for β-lactam treatment in these patients when using standard intermittent bolus dosing, even for the most conservative target (50% fT>MIC). Prolonged infusion of β-lactams has consistently been shown to improve PK/PD target attainment, particularly in patients with severe infections. However, evidence regarding relevant patient outcomes is still limited. Whereas previous observational studies have suggested a clinical benefit of prolonged infusion, results from two recent randomised controlled trials of continuous infusion versus intermittent bolus administration of β-lactams are conflicting. In particular, the larger, double-blind placebo-controlled randomised controlled trial including 443 patients did not demonstrate any difference in clinical outcomes. We believe that a personalised approach is required to truly optimise β-lactam treatment in critically ill patients. This may include therapeutic drug monitoring with real-time adaptive feedback, rapid MIC determination and the use of antibiotic dosing software tools that incorporate patient parameters, dosing history, drug concentration and site of infection. Universal administration of β-lactam antibiotics as prolonged infusion, even if supported by therapeutic drug monitoring, is not yet ready for "prime time", as evidence for its clinical benefit is modest. There is a need for prospective randomised controlled trials that assess patient-centred outcomes (e.g. mortality) of a personalised approach in selected critically ill patients including prolonged infusion of β-lactams compared with the current standard of care

Temporal trends in mortality and provision of intensive care in younger women and men with acute myocardial infarction or stroke

BACKGROUND Timely management of acute myocardial infarction (AMI) and acute stroke has undergone impressive progress during the last decade. However, it is currently unknown whether both sexes have profited equally from improved strategies. We sought to analyze sex-specific temporal trends in intensive care unit (ICU) admission and mortality in younger patients presenting with AMI or stroke in Switzerland. METHODS Retrospective analysis of temporal trends in 16,954 younger patients aged 18 to ≤ 52 years with AMI or acute stroke admitted to Swiss ICUs between 01/2008 and 12/2019. RESULTS Over a period of 12 years, ICU admissions for AMI decreased more in women than in men (- 6.4% in women versus - 4.5% in men, p < 0.001), while ICU mortality for AMI significantly increased in women (OR 1.2 [1.10-1.30], p = 0.032), but remained unchanged in men (OR 0.99 [0.94-1.03], p = 0.71). In stroke patients, ICU admission rates increased between 3.6 and 4.1% per year in both sexes, while ICU mortality tended to decrease only in women (OR 0.91 [0.85-0.95, p = 0.057], but remained essentially unaltered in men (OR 0.99 [0.94-1.03], p = 0.75). Interventions aimed at restoring tissue perfusion were more often performed in men with AMI, while no sex difference was noted in neurovascular interventions. CONCLUSION Sex and gender disparities in disease management and outcomes persist in the era of modern interventional neurology and cardiology with opposite trends observed in younger stroke and AMI patients admitted to intensive care. Although our study has several limitations, our data suggest that management and selection criteria for ICU admission, particularly in younger women with AMI, should be carefully reassessed

Diagnostic challenges within the Bacillus cereus-group: finding the beast without teeth

The Bacillus cereus-group (B. cereus sensu lato) includes common, usually avirulent species, often considered contaminants of patient samples in routine microbiological diagnostics, as well as the highly virulent B. anthracis. Here we describe 16 isolates from 15 patients, identified as B. cereus-group using a MALDI-TOF MS standard database. Whole genome sequencing (WGS) analysis identified five of the isolates as B. anthracis species not carrying the typical virulence plasmids pXO1 and pXO2, four isolates as B. paranthracis, three as B. cereus sensu stricto, two as B. thuringiensis, one as B. mobilis, and one isolate represents a previously undefined species of Bacillus (B. basilensis sp. nov.). More detailed analysis using alternative MALDI-TOF MS databases, biochemical phenotyping, and diagnostic PCRs, gave further conflicting species results. These cases highlight the difficulties in identifying avirulent B. anthracis within the B. cereus-group using standard methods. WGS and alternative MALDI-TOF MS databases offer more accurate species identification, but so far are not routinely applied. We discuss the diagnostic resolution and discrepancies of various identification methods