Personalised perioperative dosing of ivabradine in noncardiac surgery: a single-centre, randomised, placebo-controlled, double-blind feasibility pilot trial.

BACKGROUND: Perioperative myocardial injury after noncardiac surgery is associated with postoperative mortality. Heart rate (HR) is an independent risk factor for perioperative myocardial injury. In this pilot trial we tested the feasibility of a randomised, placebo-controlled trial of personalised HR-targeted perioperative ivabradine. METHODS: This was a single-centre, randomised, placebo-controlled, double-blind, parallel group, feasibility pilot trial conducted at Geneva University Hospitals. We included patients ≥75 yr old or ≥45 yr old with cardiovascular risk factors planned for intermediate- or high-risk surgery. Patients were randomised to receive ivabradine (2.5, 5.0, or 7.5 mg) or placebo according to their HR, twice daily, from the morning of surgery until postoperative day 2. Primary outcomes were appropriate dosage and blinding success rates. RESULTS: Between October 2020 and January 2022, we randomised 78 patients (recruitment rate of 1.3 patients week-1). Some 439 of 444 study drug administrations were adequate (99% appropriate dosage rate). The blinding success rate was 100%. There were 137 (31%) administrations of Pill A (placebo in both groups for HR ≤70 beats min-1). Nine (11.5%) patients had a high-sensitive cardiac troponin T elevation ≥14 ng L-1 between any two measurements. The number of bradycardia episodes was eight in the placebo group and nine in the ivabradine group. CONCLUSIONS: This pilot study demonstrates the feasibility of, and provides guidance for, a future trial testing the efficacy of personalised perioperative ivabradine. Future studies should include patients at higher risk of cardiac complications. CLINICAL TRIAL REGISTRATION: NCT04436016.

ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation

In recent years, there has been increasing focus on the use of cardiac biomarkers in patients undergoing noncardiac surgery. The aim of this focused guideline was to provide updated guidance regarding the pre-, post- and combined pre-and postoperative use of cardiac troponin and B-type natriuretic peptides in adult patients undergoing noncardiac surgery. The guidelines were prepared using Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. This included the definition of critical outcomes, a systematic literature search, appraisal of certainty of evidence, evaluation of biomarker measurement in terms of the balance of desirable and undesirable effects including clinical outcomes, resource use, health inequality, stakeholder acceptance, and implementation. The panel differentiated between three different scopes of applications: cardiac biomarkers as prognostic factors, as tools for risk prediction, and for biomarker-enhanced management strategies. In a modified Delphi process, the task force defined 12 critical outcomes. The systematic literature search resulted in over 25,000 hits, of which 115 full-text articles formed the body of evidence for recommendations. The evidence appraisal indicated heterogeneity in the certainty of evidence across critical outcomes. Further, there was relevant gradient in the certainty of evidence across the three scopes of application. Recommendations were issued and if this was not possible due to limited evidence, clinical practice statements were produced. The ESAIC focused guidelines provide guidance on the perioperative use of cardiac troponin and B-type natriuretic peptides in patients undergoing noncardiac surgery, for three different scopes of application.

ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation.

BACKGROUND: In recent years, there has been increasing focus on the use of cardiac biomarkers in patients undergoing noncardiac surgery. AIMS: The aim of this focused guideline was to provide updated guidance regarding the pre-, post- and combined pre-and postoperative use of cardiac troponin and B-type natriuretic peptides in adult patients undergoing noncardiac surgery. METHODS: The guidelines were prepared using Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. This included the definition of critical outcomes, a systematic literature search, appraisal of certainty of evidence, evaluation of biomarker measurement in terms of the balance of desirable and undesirable effects including clinical outcomes, resource use, health inequality, stakeholder acceptance, and implementation. The panel differentiated between three different scopes of applications: cardiac biomarkers as prognostic factors, as tools for risk prediction, and for biomarker-enhanced management strategies. RESULTS: In a modified Delphi process, the task force defined 12 critical outcomes. The systematic literature search resulted in over 25,000 hits, of which 115 full-text articles formed the body of evidence for recommendations. The evidence appraisal indicated heterogeneity in the certainty of evidence across critical outcomes. Further, there was relevant gradient in the certainty of evidence across the three scopes of application. Recommendations were issued and if this was not possible due to limited evidence, clinical practice statements were produced. CONCLUSION: The ESAIC focused guidelines provide guidance on the perioperative use of cardiac troponin and B-type natriuretic peptides in patients undergoing noncardiac surgery, for three different scopes of application.

Changes of health-related quality of life 6 months after high-risk oncological upper gastrointestinal and hepatobiliary surgery: a single-centre prospective observational study (ChangeQol Study).

INTRODUCTION: Postoperative health-related quality of life (HRQoL) is an essential outcome in oncological surgery, particularly for elderly patients undergoing high-risk surgery. Previous studies have suggested that, on average, HRQoL returns to premorbid normal levels in the months following major surgery. However, the averaging of effect over a studied cohort may hide the variation of individual HRQoL changes. The proportions of patients who have a varied HRQoL response (stable, improvement, or a deterioration) after major oncological surgery is poorly understood. The study aims to describe the patterns of these HRQoL changes at 6 months after surgery, and to assess the patients and next-of-kin regret regarding the decision to undergo surgery. METHODS AND ANALYSIS: This prospective observational cohort study is carried out at the University Hospitals of Geneva, Switzerland. We include patients over 18 years old undergoing gastrectomy, esophagectomy, pancreas resection or hepatectomy. The primary outcome is the proportion of patients in each group with changes in HRQoL (improvement, stability or deterioration) 6 months after surgery, using a validated minimal clinically important difference of 10 points in HRQoL. The secondary outcome is to assess whether patients and their next-of-kin may regret their decision to undergo surgery at 6 months. We measure the HRQoL using the EORTC QLQ-C30 questionnaire before and 6 months after surgery. We assess regret with the Decision Regret Scale (DRS) at 6 months after surgery. Key other perioperative data include preoperative and postoperative place of residence, preoperative anxiety and depression (HADS scale), preoperative disability (WHODAS V.2.0), preoperative frailty (Clinical Frailty Scale), preoperative cognitive function (Mini-Mental State Examination) and preoperative comorbidities. A follow-up at 12 months is planned. ETHICS AND DISSEMINATION: The study was first approved by the Geneva Ethical Committee for Research (ID 2020-00536) on 28 April 2020. The results of this study will be presented at national and international scientific meetings, and publications will be submitted to an open-access peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04444544.

Three-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM): French translation and cultural adaptation.

PURPOSE: The routine use of validated diagnostic instruments is key to identifying delirious patients early and expediting care. The 3-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM) instrument is a brief, easy to use, sensitive, and specific delirium assessment tool for hospitalized patients. We aimed to translate the original English version into French, and then adapt it to older high-risk patients. METHODS: Translation and adaptation of the questionnaire were guided by an expert committee and the 3D-CAM instrument developer. During the translation phase, we achieved semantic and conceptual equivalence of the instrument by conducting forward and backward translations. During the adaptation phase, we assessed the face validity, clarity of wording, and ease of use of the translated questionnaire by administering it to 30 patients and their caregivers in peri-interventional and medical intermediate care units. During both phases, we used qualitative (goal and adequacy of the questionnaire) and quantitative (Sperber score, clarity score) criteria. RESULTS: Translation: four items were judged inadequate and were revised until all reached a Sperber score of < 3/7. Face validity: 91% of patients thought the questionnaire was designed to assess memory, thoughts, or reasoning. Clarity: eight items required adjustments until all scored ≥ 9/10 for clarity. Ease of use: all bedside caregivers reported that the questionnaire was easy to complete after receiving brief instructions. CONCLUSIONS: We produced a culturally adapted French version of the 3D-CAM instrument that is well understood and well-received by older high-risk patients and their caregivers.

RéSUMé: OBJECTIF: L'administration systématique d'instruments diagnostiques validés est essentielle pour identifier précocement les patients confus. Le questionnaire 3D-CAM (3 Minute Diagnostic Confusion Assessment Method) est un outil d'évaluation bref, facile à administrer en milieu hospitalier, sensible et spécifique pour l'état confusionnel. Notre objectif était de le traduire en français, puis de l'adapter à une population de patients âgés à haut risque. MéTHODE: La traduction et l'adaptation ont été guidées par un comité d'experts et le développeur de l'instrument. Nous avons atteint une équivalence sémantique et conceptuelle en menant des traductions antérogrades, puis rétrogrades. Nous avons évalué la validité de contenu, la clarté lexicale, et la facilité d'administration du questionnaire en le soumettant à 30 patients et 30 soignants dans des unités de soins intermédiaires médicaux et péri-interventionnels. Durant les phases de traduction et d'adaptation, nous avons utilisé des critères qualitatifs et quantitatifs. RéSULTATS: Traduction : quatre questions ont été jugées inadéquates et ont été révisées pour atteindre un score de Sperber < 3/7. Validité de contenu : 91% des patients pensaient que le questionnaire était conçu pour évaluer la mémoire, les pensées, ou le raisonnement. Clarté : huit questions ont dû être modifiées pour atteindre un score de clarté ≥ 9/10. Facilité d'administration : tous les soignants pensaient que le questionnaire était facile à utiliser après une brève formation. CONCLUSIONS: Nous avons produit une version française du questionnaire 3D-CAM qui est adaptée aux patients âgés à haut risque et aux soignants en milieu de soins aigus.

Impact of Acute Inflammation on Cytochromes P450 Activity Assessed by the Geneva Cocktail.

Cytochromes P450 (CYP) are subject to important interindividual variability in their activity due to genetic and environmental factors and some diseases. Limited human data support the idea that inflammation downregulates CYP activities. Our study aimed to evaluate the impact of orthopedic surgery (acute inflammation model) on the activity of six human CYP. This prospective observational study was conducted in 30 patients who underwent elective hip surgery at the Geneva University Hospitals in Switzerland. The Geneva phenotyping cocktail containing caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, and midazolam as probe drugs respectively assessing CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A activities was administered orally before surgery, day 1 (D1) and 3 (D3) postsurgery and at discharge. Capillary blood samples were collected 2 hours after cocktail intake to assess metabolic ratios (MRs). Serum inflammatory markers (CRP, IL-6, IL-1ß, TNF-α, and IFN-γ) were also measured in blood. CYP1A2 MRs decreased by 53% (P < 0.0001) between baseline and the nadir at D1. CYP2C19 and CYP3A activities (MRs) decreased by 57% (P = 0.0002) and 61% (P < 0.0001), respectively, with the nadir at D3. CYP2B6 and CYP2C9 MRs increased by 120% (P < 0.0001) and 79% (P = 0.018), respectively, and peaked at D1. Surgery did not have a significant impact on CYP2D6 MR. Hip surgery was a good acute inflammation model as CRP, IL-6, and TNF-α peak levels were reached between D1 and day 2 (D2). Acute inflammation modulated CYP activity in an isoform-specific manner, with different magnitudes and kinetics. Acute inflammation may thus have a clinically relevant impact on the pharmacokinetics of these CYP substrates.

Effect of ivabradine on major adverse cardiovascular events and mortality in critically ill patients: a systematic review and meta-analyses of randomised controlled trials with trial sequential analyses.

BACKGROUND: Ivabradine lowers heart rate (HR) without affecting contractility or vascular tone. It is licensed for HR control in chronic heart diseases. We performed a systematic review and meta-analyses to examine whether ivabradine could decrease major adverse cardiovascular events (MACE) and mortality in critically ill patients. METHODS: We searched Medline, Embase, Cochrane Library, and Web of Science for RCTs. Trial quality was assessed using the Cochrane risk of bias tool. Random-effects meta-analyses were performed if at least three trials or 100 patients were available. Results are reported as weighted mean difference (WMD), odds ratio (OR), and 95% confidence intervals (CIs). Trial sequential analyses were performed to estimate the sample size needed to reach definitive conclusions of efficacy or futility. RESULTS: We included 13 RCTs (n=1497 patients). We found no evidence of an impact of ivabradine on MACE (three RCTs, 819 patients; OR=0.77; 95% CI, 0.53-1.11) or mortality (10 RCTs, 1356 patients; OR=1.07; 95% CI, 0.63-1.82), but sample sizes were not reached to allow definitive conclusions. Compared with placebo or standard care, ivabradine reduced HR (eight RCTs, 464 patients; WMD, -9.5 beats min-1; 95% CI, -13.3 to -5.8). Risk of bradycardia was not different between ivabradine and control (five RCTs, 434 patients; OR=1.2; 95% CI, 0.60-2.38). Risk of bias was overall high or unclear. CONCLUSIONS: Ivabradine reduces HR compared with placebo or standard care. The effect on MACE or mortality in acute care remains unclear. Further RCTs powered to detect changes in clinically relevant outcomes are warranted. CLINICAL TRIAL REGISTRATION: Prospero CRD42018086109.

Prediction of long-term quality of life after severe traumatic brain injury based on variables at hospital admission.

Objectives: Variables collected early after severe traumatic brain injury (sTBI) could predict health-related quality of life (HRQoL). Our aim was to determine the prevalence of patients with a low HRQoL 4 years after sTBI and to develop a prediction model including early variables.Methods: Adult patients with both sTBI [abbreviated injury score of the head region (HAIS) >3] and disease-specific HRQoL assessments using the 'Quality of Life after Brain Injury' (QOLIBRI) were included. The outcome was the total score (TS) of QOLIBRI; cutoff for low HRQoL: <60 points. A multivariate logistic regression model and prediction model were performed.Results: One hundred-sixteen patients [median age 50.8 years (IQR 25.9-62.8; 21.6% >65 years)] were included; 68 (58.6%) with HAIS = 4, 48 (41.4%) with HAIS = 5. Median Glasgow Coma Scale (GCS) was 13 (IQR 3-15). Median TS was 77 (IQR 60-88). Low HRQoL was observed in 28 patients (24.1%). Two variables were associated with low HRQoL: GCS <13, working situation other than employed or retired. The prediction model had an AUROC of 0.765; calibration was moderate (Hosmer Lemeshow Chi2 6.82, p = .556).Conclusion: One in four patients had a low HRQoL after 4 years. A lower GCS and working situations were associated with low HRQoL.

Validation of the clinical frailty score (CFS) in French language.

BACKGROUND: Very old critical ill patients are a rapid expanding group. To better understand the magnitude of the challenges involved in intensive care practice for an ageing population and discuss a rational allocation of resources, healthcare practitioners need a reliable evaluation of frailty. In order to promote the adequate use of the Clinical Frailty Scale (CFS) in a wider panel of countries, we aimed to develop, validate and characterise a French (FR) version from the original English (EN) CFS. METHODS: We included participants recruited prospectively for the observational "The very old intensive care patient: A multinational prospective observation study" (VIP Study) at Geneva University Hospitals (FR speaking hospital). A FR version of the CFS was obtained by translation (EN- > FR) and back translation (FR- > EN). The final CFS-FR was then evaluated twice on the same participants with at least a 2-week interval by FR-speaking doctors and nurses. RESULTS: Inter-rater reliability was 0.87 (95%CI: 0.76-0.93) between doctors for the original CFS version and 0.76 (95%CI: 0.57-0.87) between nurses for the FR version. Inter-rater variability between doctor and nurse was 0.75 (95%CI: 0.56-0.87) for the original version, and 0.73 (95%CI: 0.52-0.85) for the FR version. Test-retest (stability) with the original vs the FR version was 0.86 (95%CI: 0.72-0.93) for doctors and 0.87 (95%CI: 0.76-0.93) for nurses. Differences between the evaluations of the CFS-EN and CSF-FR were not different from 0, with a mean difference of 0.06 (95%CI -0.24, 0.36) for the EN version and - 0.03 (95%CI -0.47, 0.41) for the FR version. Average original version ratings were slightly lower than FR version ratings, though this difference did not reach significance: -0.29 (95%CI -0.54, 0.04). CONCLUSION: In this prospective cohort of very old intensive care participants we developed and tested the basic psychometric properties (internal consistency, reproducibility) of a French version of the CFS. This manuscript provides clinically meaningful psychometric properties that have not been previously reported in any other language, including in the original EN version. The French cultural adaptation of this CFS has adequate psychometric properties for doctors or nurses to evaluate frailty in very old intensive care patients.

The concept of peri-operative medicine to prevent major adverse events and improve outcome in surgical patients: A narrative review.

: Peri-operative Medicine is the patient-centred and value-based multidisciplinary peri-operative care of surgical patients. Peri-operative stress, that is the collective response to stimuli occurring before, during and after surgery, is, together with pre-existing comorbidities, the pathophysiological basis of major adverse events. The ultimate goal of Peri-operative Medicine is to promote high quality recovery after surgery. Clinical scores and/or biomarkers should be used to identify patients at high risk of developing major adverse events throughout the peri-operative period. Allocation of high-risk patients to specific care pathways with peri-operative organ protection, close surveillance and specific early interventions is likely to improve patient-relevant outcomes, such as disability, health-related quality of life and mortality.

Determinants of hospital length of stay after transcatheter aortic valve implantation with self-expanding prostheses: a prospective, single centre observational study.

INTRODUCTION: We sought to identify baseline and periprocedural variables affecting hospital length of stay (LoS) in patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: Data on 304 consecutive patients undergoing TAVI at a single centre between August 2008 and December 2017 were collected prospectively. All patients underwent a complete clinical, echocardiographic and laboratory evaluation including a comprehensive frailty assessment at baseline. LoS was defined as the number of in-hospital days after the TAVI procedure during the index hospitalisation until the time the patient left the hospital for home or a rehabilitation clinic. RESULTS: The mean LoS was 10.4 ± 7.1 days (median 8, interquartile range 5–12) with a significant trend towards shorter LoS over time (p <0.001). Patients discharged directly home were more likely to have shorter LoS (p = 0.007). All periprocedural complications were significantly associated with prolonged LoS (p <0.05 for all). Multivariate analysis showed an independent association between LoS and emergency admission (beta 3.24 ± 1.56, p = 0.039), baseline gait speed (beta: 0.39 ± 0.16, p = 0.018), baseline serum C-reactive protein (CRP, beta 0.14 ± 0.04, p = 0.001) and subclavian access (beta 8.27 ± 2 .9, p = 0.005). Gait speed and serum CRP remained significant determinants of LoS even after adjustment for periprocedural complications and patients’ discharge destination. CONCLUSION: Baseline gait speed and serum CRP are significant independent determinants of LoS after TAVI.

Prehospital and Emergency Care in Adult Patients with Acute Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major healthcare problem and a major burden to society. The identification of a TBI can be challenging in the prehospital setting, particularly in elderly patients with unobserved falls. Errors in triage on scene cannot be ruled out based on limited clinical diagnostics. Potential new mobile diagnostics may decrease these errors. Prehospital care includes decision-making in clinical pathways, means of transport, and the degree of prehospital treatment. Emergency care at hospital admission includes the definitive diagnosis of TBI with, or without extracranial lesions, and triage to the appropriate receiving structure for definitive care. Early risk factors for an unfavorable outcome includes the severity of TBI, pupil reaction and age. These three variables are core variables, included in most predictive models for TBI, to predict short-term mortality. Additional early risk factors of mortality after severe TBI are hypotension and hypothermia. The extent and duration of these two risk factors may be decreased with optimal prehospital and emergency care. Potential new avenues of treatment are the early use of drugs with the capacity to decrease bleeding, and brain edema after TBI. There are still many uncertainties in prehospital and emergency care for TBI patients related to the complexity of TBI patterns.

Comparison of two simple models for prediction of short term mortality in patients after severe traumatic brain injury.

INTRODUCTION: The subscale motor score of Glasgow Coma Scale (msGCS) and the Abbreviated Injury Score of head region (HAIS) are validated prognostic factors in traumatic brain injury (TBI). The aim was to compare the prognostic performance of a HAIS-based prediction model including HAIS, pupil reactivity and age, and the reference prediction model including msGCS in emergency department (ED), pupil reactivity and age. METHODS: Secondary analysis of a prospective epidemiological study including patients after severe TBI (HAIS > 3) with follow-up from the time of accident until 14 days or earlier death was performed in Switzerland. Performance of prediction, based on accuracy of discrimination [area under the receiver-operating curve (AUROC)], calibration (Hosmer-Lemeshow test) and validity (bootstrapping with 2000 repetitions to correct) for optimism of the two prediction models were investigated. A non-inferiority approach was performed and an a priori threshold for important differences was established. RESULTS: The cohort included 808 patients [median age 56 {inter-quartile range (IQR) 33-71}, median motor part of GCS in ED 1 (1-6), abnormal pupil reactivity 29.0%] with a death rate of 29.7% at 14 days. The accuracy of discrimination was similar (AUROC HAIS-based prediction model: 0.839; AUROC msGCS-based prediction model: 0.826, difference of the 2 AUROC 0.013 (-0.007 to 0.037). A similar calibration was observed (Hosmer-Lemeshow X2 11.64, p = 0.168 vs. Hosmer-Lemeshow X2 8.66, p = 0.372). Internal validity of HAIS-based prediction model was high (optimism corrected AUROC: 0.837). CONCLUSIONS: Performance of prediction for short-term mortality after severe TBI with HAIS-based prediction model was non-inferior to reference prediction model using msGCS as predictor.

Comparison of two prehospital predictive models for mortality and impaired consciousness after severe traumatic brain injury.

BACKGROUND: The primary aim was to investigate the performance of a National Advisory Committee for Aeronautics based predictive model (NACA-BM) for mortality at 14 days and a reference model using motor GCS (GCS-RM). The secondary aim was to compare the models for impaired consciousness of survivors at 14 days (IC-14; GCS ≤ 13). METHODS: Patients ≥16 years having sustained TBI with an abbreviated injury scale score of head region (HAIS) of >3 were included. Multivariate logistic regression models were used to test models for death and IC-14. The discrimination was assessed using area under the receiver-operating curves (AUROCs); noninferiority margin was -5% between the AUROCs. Calibration was assessed using the Hosmer Lemeshow goodness-of-fit test. RESULTS: Six hundred and seventy seven patients were included. The median age was 54 (IQR 32-71). The mortality rate was 31.6%; 99 of 438 surviving patients (22.6%) had an IC-14. Discrimination of mortality was 0.835 (95%CI 0.803-0.867) for the NACA-BM and 0.839 (0.807-0.872) for the GCS-RM; the difference of the discriminative ability was -0.4% (-2.3% to +1.7%). Calibration was appropriate for the NACA-BM (χ2 8.42; P = 0. 393) and for the GCS-RM (χ2 3.90; P = 0. 866). Discrimination of IC-14 was 0.757 (0.706-0.808) for the NACA-BM and 0.784 (0.734-0.835) for the GCS-RM; the difference of the discriminative ability was -2.5% (-7.8% to +2.6%). Calibration was appropriate for the NACA-BM (χ2 10.61; P = 0.225) and for the GCS-RM (χ2 6.26; P = 0.618). CONCLUSIONS: Prehospital prediction of mortality after TBI was good with both models, and the NACA-BM was not inferior to the GCS-RM. Prediction of IC-14 was moderate in both models.

Patient-Controlled Versus Clinician-Controlled Sedation With Propofol: Systematic Review and Meta-analysis With Trial Sequential Analyses.

BACKGROUND: Sedation with propofol is frequently used to facilitate diagnostic and therapeutic procedures. Propofol can be administrated by the patient (patient-controlled sedation [PCS]) or by a clinician (clinician-controlled sedation [CCS]). We aimed to compare these 2 techniques. METHODS: PubMed, Embase, CENTRAL, and trial registries were searched up to October 2017 for randomized controlled trials comparing PCS with CCS with propofol. The primary end points were the risks of presenting at least 1 episode of oxygen desaturation, arterial hypotension, and bradycardia, and the risk of requiring a rescue intervention (pharmacologic therapies or physical maneuvers) for sedation-related adverse events. Secondary end points were the dose of propofol administrated, operator and patient satisfaction, and the risk of oversedation. A random-effects model and an α level of .02 to adjust for multiple analyses were used throughout. Trial sequential analyses were performed for primary outcomes. Quality of evidence was assessed according to the Grades of Recommendation, Assessment, Development, and Evaluation system. RESULTS: Thirteen trials (1103 patients; median age, 47 years; American Society of Anesthesiologists physical status I-III) describing various diagnostic and therapeutic procedures with propofol sedation were included. PCS had no impact on the risk of oxygen desaturation (11 trials, 31/448 patients [6.9%] with PCS versus 46/481 [9.6%] with CCS; risk ratio, 0.74 [98% confidence interval, 0.35-1.56]) but decreased the risk of requiring a rescue intervention for adverse events (11 trials, 29/449 patients [6.5%] with PCS versus 74/482 [15.4%] with CCS; risk ratio, 0.45 [98% confidence interval, 0.25-0.81]). For both outcomes, Trial sequential analyses suggested that further trials were unlikely to change the results, although the quality of evidence was graded very low for all primary outcomes. For the risk of arterial hypotension and bradycardia, the required sample size for a definitive conclusion had not been reached. Analysis of secondary outcomes suggested that PCS decreased the risk of oversedation and had no impact on propofol dose administrated, or on operator or patient satisfaction. CONCLUSIONS: PCS with propofol, compared with CCS with propofol, had no impact on the risk of oxygen desaturation, but significantly decreased the risk of rescue interventions for sedation-related adverse events. Further high-quality trials are required to assess the risks and benefits of PCS.

Prevention of hospital infections by intervention and training (PROHIBIT): results of a pan-European cluster-randomized multicentre study to reduce central venous catheter-related bloodstream infections.

PURPOSE: To test the effectiveness of a central venous catheter (CVC) insertion strategy and a hand hygiene (HH) improvement strategy to prevent central venous catheter-related bloodstream infections (CRBSI) in European intensive care units (ICUs), measuring both process and outcome indicators. METHODS: Adult ICUs from 14 hospitals in 11 European countries participated in this stepped-wedge cluster randomised controlled multicentre intervention study. After a 6 month baseline, three hospitals were randomised to one of three interventions every quarter: (1) CVC insertion strategy (CVCi); (2) HH promotion strategy (HHi); and (3) both interventions combined (COMBi). Primary outcome was prospective CRBSI incidence density. Secondary outcomes were a CVC insertion score and HH compliance. RESULTS: Overall 25,348 patients with 35,831 CVCs were included. CRBSI incidence density decreased from 2.4/1000 CVC-days at baseline to 0.9/1000 (p < 0.0001). When adjusted for patient and CVC characteristics all three interventions significantly reduced CRBSI incidence density. When additionally adjusted for the baseline decreasing trend, the HHi and COMBi arms were still effective. CVC insertion scores and HH compliance increased significantly with all three interventions. CONCLUSIONS: This study demonstrates that multimodal prevention strategies aiming at improving CVC insertion practice and HH reduce CRBSI in diverse European ICUs. Compliance explained CRBSI reduction and future quality improvement studies should encourage measuring process indicators.

Integrated Health Care Management of Moderate to Severe TBI in Older Patients-A Narrative Review.

PURPOSE OF REVIEW: Traumatic brain injuries are common, especially within the elderly population, which is typically defined as age 65 and older. This narrative review aims at summarizing and critically evaluating important aspects of their health care management in covering the entire pathway from prehospital care to rehabilitation and beyond. RECENT FINDINGS: The number of older patients with traumatic brain injury (TBI) is increasing, and there seem to be differences in all aspects of care along their pathway when compared to younger patients. Despite a higher mortality and a generally less favorable outcome, the current literature shows that older TBI patients have the potential to make significant improvements over time. More research is needed to evaluate the most efficient and integrated clinical pathway from prehospital interventions to rehabilitation as well as the optimal treatment of older TBI patients. Most importantly, they should not be denied access to specific treatments and therapies only based on age.