Extracellular vesicle Cystatin C and CD14 are associated with both renal dysfunction and heart failure.

AIMS: Extracellular vesicles (EVs) are small double-membrane plasma vesicles that play key roles in cellular crosstalk and mechanisms such as inflammation. The role of EVs in combined organ failure such as cardiorenal syndrome has not been investigated. The aim of this study is to identify EV proteins that are associated with renal dysfunction, heart failure, and their combination in dyspnoeic patients. METHODS AND RESULTS: Blood samples were prospectively collected in 404 patients presenting with breathlessness at the emergency department at National University Hospital, Singapore. Renal dysfunction was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 . The presence of heart failure was independently adjudicated by two clinicians on the basis of the criteria of the European Society of Cardiology guidelines. Protein levels of SerpinG1, SerpinF2, Cystatin C, and CD14 were measured with a quantitative immune assay within three EV sub-fractions and in plasma and were tested for their associations with renal dysfunction, heart failure, and the concurrence of both conditions using multinomial regression analysis, thereby correcting for confounders such as age, gender, ethnicity, and co-morbidities. Renal dysfunction was found in 92 patients (23%), while heart failure was present in 141 (35%). In total, 58 patients (14%) were diagnosed with both renal dysfunction and heart failure. Regression analysis showed that Cystatin C was associated with renal dysfunction, heart failure, and their combination in all three EV sub-fractions and in plasma. CD14 was associated with both renal dysfunction and the combined renal dysfunction and heart failure in all EV sub-fractions, and with presence of heart failure in the high density lipoprotein sub-fraction. SerpinG1 and SerpinF2 were associated with heart failure in, respectively, two and one out of three EV sub-fractions and in plasma, but not with renal dysfunction. CONCLUSIONS: We provide the first data showing that Cystatin C and CD14 in circulating EVs are associated with both renal dysfunction and heart failure in patients presenting with acute dyspnoea. This suggests that EV proteins may be involved in the combined organ failure of the cardiorenal syndrome and may represent possible targets for prevention or treatment.

Prediction models for development of retinopathy in people with type 2 diabetes: systematic review and external validation in a Dutch primary care setting.

AIMS/HYPOTHESIS: The aims of this study were to identify all published prognostic models predicting retinopathy risk applicable to people with type 2 diabetes, to assess their quality and accuracy, and to validate their predictive accuracy in a head-to-head comparison using an independent type 2 diabetes cohort. METHODS: A systematic search was performed in PubMed and Embase in December 2019. Studies that met the following criteria were included: (1) the model was applicable in type 2 diabetes; (2) the outcome was retinopathy; and (3) follow-up was more than 1 year. Screening, data extraction (using the checklist for critical appraisal and data extraction for systemic reviews of prediction modelling studies [CHARMS]) and risk of bias assessment (by prediction model risk of bias assessment tool [PROBAST]) were performed independently by two reviewers. Selected models were externally validated in the large Hoorn Diabetes Care System (DCS) cohort in the Netherlands. Retinopathy risk was calculated using baseline data and compared with retinopathy incidence over 5 years. Calibration after intercept adjustment and discrimination (Harrell's C statistic) were assessed. RESULTS: Twelve studies were included in the systematic review, reporting on 16 models. Outcomes ranged from referable retinopathy to blindness. Discrimination was reported in seven studies with C statistics ranging from 0.55 (95% CI 0.54, 0.56) to 0.84 (95% CI 0.78, 0.88). Five studies reported on calibration. Eight models could be compared head-to-head in the DCS cohort (N = 10,715). Most of the models underestimated retinopathy risk. Validating the models against different severities of retinopathy, C statistics ranged from 0.51 (95% CI 0.49, 0.53) to 0.89 (95% CI 0.88, 0.91). CONCLUSIONS/INTERPRETATION: Several prognostic models can accurately predict retinopathy risk in a population-based type 2 diabetes cohort. Most of the models include easy-to-measure predictors enhancing their applicability. Tailoring retinopathy screening frequency based on accurate risk predictions may increase the efficiency and cost-effectiveness of diabetic retinopathy care. REGISTRATION: PROSPERO registration ID CRD42018089122.

Artifact Processing Methods Influence on Intraoperative Hypotension Quantification and Outcome Effect Estimates.

BACKGROUND: Physiologic data that is automatically collected during anesthesia is widely used for medical record keeping and clinical research. These data contain artifacts, which are not relevant in clinical care, but may influence research results. The aim of this study was to explore the effect of different methods of filtering and processing artifacts in anesthesiology data on study findings in order to demonstrate the importance of proper artifact filtering. METHODS: The authors performed a systematic literature search to identify artifact filtering methods. Subsequently, these methods were applied to the data of anesthesia procedures with invasive blood pressure monitoring. Different hypotension measures were calculated (i.e., presence, duration, maximum deviation below threshold, and area under threshold) across different definitions (i.e., thresholds for mean arterial pressure of 50, 60, 65, 70 mmHg). These were then used to estimate the association with postoperative myocardial injury. RESULTS: After screening 3,585 papers, the authors included 38 papers that reported artifact filtering methods. The authors applied eight of these methods to the data of 2,988 anesthesia procedures. The occurrence of hypotension (defined with a threshold of 50 mmHg) varied from 24% with a median filter of seven measurements to 55% without an artifact filtering method, and between 76 and 90% with a threshold of 65 mmHg. Standardized odds ratios for presence of hypotension ranged from 1.16 (95% CI, 1.07 to 1.26) to 1.24 (1.14 to 1.34) when hypotension was defined with a threshold of 50 mmHg. Similar variations in standardized odds ratios were found when applying methods to other hypotension measures and definitions. CONCLUSIONS: The method of artifact filtering can have substantial effects on estimates of hypotension prevalence. The effect on the association between intraoperative hypotension and postoperative myocardial injury was relatively small. Nevertheless, the authors recommend that researchers carefully consider artifacts handling and report the methodology used.

Anaesthesia geriatric evaluation to guide patient selection for preoperative multidisciplinary team care in cardiac surgery.

BACKGROUND: A multidisciplinary approach to improve postoperative outcomes in frail elderly patients is gaining interest. Multidisciplinary team care should be targeted at complex patients at high risk for adverse postoperative outcome to limit the strain on available resources and to prevent an unnecessary increase in patient burden. This study aimed to improve patient selection for multidisciplinary care by identifying risk factors for disability after cardiac surgery in elderly patients. METHODS: This was a two-centre prospective cohort study of 537 patients aged ≥70 yr undergoing elective cardiac surgery. Before surgery, 11 frailty characteristics were investigated. Outcome was disability at 3 months defined as World Health Organization Disability Assessment Schedule 2.0 ≥25%. Multivariable modelling using logistic regression, concordance statistic (c-statistic), and net reclassification index was used to identify factors contributing to patient selection. RESULTS: Disability occurred in 91 (17%) patients. Ten out of 11 frailty characteristics were associated with disability. A multivariable model, including the European System for Cardiac Operative Risk Evaluation II and preoperative haemoglobin, yielded a c-statistic of 0.71 (95% confidence interval [CI]: 0.66-0.77). After adding pre-specified frailty characteristics (polypharmacy, gait speed, physical disability, preoperative health-related quality of life, and living alone) to this model, the c-statistic improved to 0.78 (95% CI: 0.73-0.83). The net reclassification index was 0.32 (P<0.001), showing improved discrimination for patients at risk for disability at 3 months. CONCLUSIONS: The addition of preoperative frailty characteristics to a multivariable model improved discrimination between elderly patients with and without disability at 3 months after cardiac surgery, and can be used to guide patient selection for preoperative multidisciplinary team care. CLINICAL TRIAL REGISTRATION: NCT02535728.

Patient and anesthesia characteristics of children with low pre-incision blood pressure: A retrospective observational study.

BACKGROUND: Intraoperative blood pressure has been suggested as a key factor for safe pediatric anesthesia. However, there is not much insight into factors that discriminate between children with low and normal pre-incision blood pressure. Our aim was to explore whether children who have a low blood pressure during anesthesia are different than those with normal blood pressure. The focus of the present study was on the pre-incision period. METHODS: This retrospective study included pediatric patients undergoing anesthesia for non-cardiac surgery at a tertiary pediatric university hospital, between 2012 and 2016. We analyzed the association between pre-incision blood pressure and patient- and anesthesia characteristics, comparing low with normal pre-incision blood pressure. This association was further explored with a multivariable linear regression. RESULTS: In total, 20 962 anesthetic cases were included. Pre-incision blood pressure was associated with age (beta -0.04 SD per year), gender (female -0.11), previous surgery (-0.15), preoperative blood pressure (+0.01 per mm Hg), epilepsy (0.12), bronchial hyperactivity (-0.18), emergency surgery (0.10), loco-regional technique (-0.48), artificial airway device (supraglottic airway device instead of tube 0.07), and sevoflurane concentration (0.03 per sevoflurane %). CONCLUSIONS: Children with low pre-incision blood pressure do not differ on clinically relevant factors from children with normal blood pressure. Although the present explorative study shows that pre-incision blood pressure is partly dependent on patient characteristics and partly dependent on anesthetic technique, other unmeasured variables might play a more important role.

Incorporating repeated measurements into prediction models in the critical care setting: a framework, systematic review and meta-analysis.

BACKGROUND: The incorporation of repeated measurements into multivariable prediction research may greatly enhance predictive performance. However, the methodological possibilities vary widely and a structured overview of the possible and utilized approaches lacks. Therefore, we [1] propose a structured framework for these approaches, [2] determine what methods are currently used to incorporate repeated measurements in prediction research in the critical care setting and, where possible, [3] assess the added discriminative value of incorporating repeated measurements. METHODS: The proposed framework consists of three domains: the observation window (static or dynamic), the processing of the raw data (raw data modelling, feature extraction and reduction) and the type of modelling. A systematic review was performed to identify studies which incorporate repeated measurements to predict (e.g. mortality) in the critical care setting. The within-study difference in c-statistics between models with versus without repeated measurements were obtained and pooled in a meta-analysis. RESULTS: From the 2618 studies found, 29 studies incorporated multiple repeated measurements. The annual number of studies with repeated measurements increased from 2.8/year (2000-2005) to 16.0/year (2016-2018). The majority of studies that incorporated repeated measurements for prediction research used a dynamic observation window, and extracted features directly from the data. Differences in c statistics ranged from - 0.048 to 0.217 in favour of models that utilize repeated measurements. CONCLUSIONS: Repeated measurements are increasingly common to predict events in the critical care domain, but their incorporation is lagging. A framework of possible approaches could aid researchers to optimize future prediction models.

The intermediate care unit as a cost-reducing critical care facility in tertiary referral hospitals: a single-centre observational study.

OBJECTIVES: To determine whether and to what extent the surgical intermediate care unit (IMCU) reduces healthcare costs. DESIGN: Retrospective cohort study. SETTING: The mixed-surgical IMCU of a tertiary academic referral hospital. PARTICIPANTS: All admissions (n=2577) from 2012 to 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measure was the hypothetical cost savings due to the presence of the IMCU. For this, each admission day was classified as either low-acuity or high-acuity, based on the Therapeutic Intervention Scoring System-28, the required specific nursing interventions and the indication for admission at the IMCU. Costs (2018) used were €463 per hospital ward, €1307 per IMCU and €2224 per intensive care unit (ICU) admission day. Savings were calculated by subtracting the actual IMCU costs from the hypothetical costs in the absence of the IMCU. RESULTS: There were 9037 admission days (n=2577 admissions) at the IMCU. The proportion of high-acuity admissions was 87.6%. Total costs at the IMCU were €11.808 888. Total hypothetical costs in absence of the IMCU were €18.115 284. Total cost savings were thus €6.306 395, or €1.576 599, per year. CONCLUSIONS: The surgical IMCU may substantially reduce societal healthcare costs, making it a cost saving alternative to ICU care. Constant adequate triage is essential to optimise its potential.

Adjusting for Disease Severity Across ICUs in Multicenter Studies.

OBJECTIVES: To compare methods to adjust for confounding by disease severity during multicenter intervention studies in ICU, when different disease severity measures are collected across centers. DESIGN: In silico simulation study using national registry data. SETTING: Twenty mixed ICUs in The Netherlands. SUBJECTS: Fifty-five-thousand six-hundred fifty-five ICU admissions between January 1, 2011, and January 1, 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: To mimic an intervention study with confounding, a fictitious treatment variable was simulated whose effect on the outcome was confounded by Acute Physiology and Chronic Health Evaluation IV predicted mortality (a common measure for disease severity). Diverse, realistic scenarios were investigated where the availability of disease severity measures (i.e., Acute Physiology and Chronic Health Evaluation IV, Acute Physiology and Chronic Health Evaluation II, and Simplified Acute Physiology Score II scores) varied across centers. For each scenario, eight different methods to adjust for confounding were used to obtain an estimate of the (fictitious) treatment effect. These were compared in terms of relative (%) and absolute (odds ratio) bias to a reference scenario where the treatment effect was estimated following correction for the Acute Physiology and Chronic Health Evaluation IV scores from all centers. Complete neglect of differences in disease severity measures across centers resulted in bias ranging from 10.2% to 173.6% across scenarios, and no commonly used methodology-such as two-stage modeling or score standardization-was able to effectively eliminate bias. In scenarios where some of the included centers had (only) Acute Physiology and Chronic Health Evaluation II or Simplified Acute Physiology Score II available (and not Acute Physiology and Chronic Health Evaluation IV), either restriction of the analysis to Acute Physiology and Chronic Health Evaluation IV centers alone or multiple imputation of Acute Physiology and Chronic Health Evaluation IV scores resulted in the least amount of relative bias (0.0% and 5.1% for Acute Physiology and Chronic Health Evaluation II, respectively, and 0.0% and 4.6% for Simplified Acute Physiology Score II, respectively). In scenarios where some centers used Acute Physiology and Chronic Health Evaluation II, regression calibration yielded low relative bias too (relative bias, 12.4%); this was not true if these same centers only had Simplified Acute Physiology Score II available (relative bias, 54.8%). CONCLUSIONS: When different disease severity measures are available across centers, the performance of various methods to control for confounding by disease severity may show important differences. When planning multicenter studies, researchers should make contingency plans to limit the use of or properly incorporate different disease measures across centers in the statistical analysis.

Cardiac events within one year after a subarachnoid haemorrhage: The predictive value of troponin elevation after aneurysm occlusion.

BACKGROUND: Patients who survive after an aneurysmal subarachnoid haemorrhage (ASAH) have an increased incidence of cardiovascular events compared with the general population. We assessed whether troponin elevation after aneurysm occlusion, as marker of myocardial injury, can predict long-term cardiac events. METHODS: We analysed a prospectively collected cohort of 159 patients with ASAH and early aneurysm occlusion, in whom routine post-intervention troponin I (TnI) measurements were performed. With competing risk regression modelling we estimated the association between TnI elevation after aneurysm occlusion and major adverse cardiac events within one year. Secondary outcome measures were all-cause mortality and neurological condition within one year. The predictive value of post-intervention TnI was compared with the predictive value of pre-intervention characteristics using c-statistics and the integrated discrimination improvement index. RESULTS: Subdistribution hazard ratios for TnI elevation and major adverse cardiac events at one year were 1.05 (95% confidence interval (CI) 1.03-1.07) per 10 ng/l increase in TnI and 7.91 (95% CI 1.46-43.0) for any TnI elevation. After adjustment for pre-intervention variables, the subdistribution hazard ratios were 1.47 (95% CI 0.81-2.67) per 10 ng/l and 9.00 (95% CI 1.62-50.1) for any elevation. The c-statistic was 0.71 for TnI elevation as a continuous measure and 0.69 for any TnI elevation. The integrated discrimination improvement index showed a minimum improvement in prediction of 0.08 (interquartile range 0.06 to 0.09) for TnI as a continuous measure and 0.003 (interquartile range -0.004 to 0.01) for any TnI elevation, when compared with pre-intervention characteristics. CONCLUSION: TnI elevation after occlusion of a ruptured intracranial aneurysm predicts the occurrence of a major adverse cardiac event within one year after ASAH.

Blood Pressure and End-tidal Carbon Dioxide Ranges during Aneurysm Occlusion and Neurologic Outcome after an Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Hypocapnia, hypotension, and hypertension during aneurysm occlusion in patients with an aneurysmal subarachnoid hemorrhage may lead to a poor prognosis, but evidence for end-tidal carbon dioxide (ETCO2) and mean arterial pressure (MAP) targets is lacking. Within the ranges of standardized treatment, the authors aimed to study the association between hypocapnia (PaCO2 < 35 mmHg), hypotension (MAP < 80 mmHg), and hypertension (MAP >100 mmHg) during general anesthesia for aneurysm occlusion and neurologic outcome. METHODS: This retrospective observational study included patients who underwent early aneurysm occlusion after an aneurysmal subarachnoid hemorrhage under general anesthesia. ETCO2 and MAP were summarized per patient as the mean and time-weighted average area under the curve for various absolute (ETCO2 < 30, < 35, < 40, < 45 mmHg; and MAP < 60, < 70, < 80, > 90, > 100 mmHg) and relative thresholds (MAP < 70%, < 60%, < 50%). Clinical outcome was assessed with the Glasgow Outcome Scale at discharge and at three months, as primary and secondary outcome measure, respectively. RESULTS: Endovascular coiling was performed in 578 patients, and 521 underwent neurosurgical clipping. Of these 1,099 patients, 447 (41%) had a poor neurologic outcome at discharge. None of the ETCO2 and MAP ranges found within the current clinical setting were associated with a poor neurologic outcome at discharge, with an adjusted risk ratio for any ETCO2 value less than 30 mmHg of 0.95 (95% CI, 0.81 to 1.10; P < 0.496) and an adjusted risk ratio for any MAP less than 60 mmHg of 0.94 (95% CI, 0.78 to 1.14; P < 0.530). These results were not influenced by preoperative neurologic condition, treatment modality and timing of the intervention. Comparable results were obtained for neurologic outcome at three months. CONCLUSIONS: Within a standardized intraoperative treatment strategy in accordance with current clinical consensus, hypocapnia, hypotension, and hypertension during aneurysm occlusion were not found to be associated with a poor neurologic outcome at discharge in patients with an aneurysmal subarachnoid hemorrhage.

Pulmonary Embolism After Endovascular Aortic Repair, a Retrospective Cohort Study.

OBJECTIVES: Endovascular aortic repair (EVAR) is associated with an increased risk of pulmonary embolism, which is often clinically silent and therefore difficult to recognise. The aim was to investigate the incidence of pulmonary embolism after EVAR using routinely performed pre- and post-operative aortic computed tomography angiography (CTA), and the association between pulmonary embolism and mortality. METHODS: This single centre retrospective cohort study included adult patients who underwent EVAR in the University Medical Centre Utrecht between January 2010 and July 2015 and who had a total aortic, thoracic aortic, or pulmonary CTA within one month post-operatively. Baseline and mortality data were obtained by reviewing hospital and general practitioner records. The primary outcome was pulmonary embolism within one month after surgery. Secondary outcomes were 30 day and six month mortality. RESULTS: During the study period, 526 EVARs were performed. Seventy-four of these procedures were included in the analysis of which there were 40 thoracic and 34 abdominal EVARs. In nine patients (12%, 95% CI 7-22) pulmonary embolism was observed of which one was central, two were segmental, and six were subsegmental. Seven were clinically silent and two were present on the pre-operative CTA. Thirty day mortality was significantly higher in patients with pulmonary embolism (relative risk 14.4, 95% CI 1.4-143, p = .037) though none of the deaths seemed directly attributable to it. CONCLUSIONS: This study, although preliminary, suggests that silent pulmonary embolism after EVAR occurs in approximately one in 10 patients, despite routine thrombo-embolism prophylaxis. Pulmonary embolism was associated with a higher 30 day mortality risk yet it was not the cause of death in any of these patients.

Causes and prevention of postoperative myocardial injury.

Over the past few years non-cardiac surgery has been recognised as a serious circulatory stress test which may trigger cardiovascular events such as myocardial infarction, in particular in patients at high risk. Detection of these postoperative cardiovascular events is difficult as clinical symptoms often go unnoticed. To improve detection, guidelines advise to perform routine postoperative assessment of cardiac troponin. Troponin elevation - or postoperative myocardial injury - can be caused by myocardial infarction. However, also non-coronary causes, such as cardiac arrhythmias, sepsis and pulmonary embolism, may play a role in a considerable number of patients with postoperative myocardial injury. It is crucial to acquire more knowledge about the underlying mechanisms of postoperative myocardial injury because effective prevention and treatment options are lacking. Preoperative administration of beta-blockers, aspirin, statins, clonidine, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and preoperative revascularisation have all been investigated as preventive options. Of these, only statins should be considered as the initiation or reload of statins may reduce the risk of postoperative myocardial injury. There is also not enough evidence for intraoperative measures such blood pressure optimisation or intensified medical therapy once patients have developed postoperative myocardial injury. Given the impact, better preoperative identification of patients at risk of postoperative myocardial injury, for example using preoperatively measured biomarkers, would be helpful to improve cardiac optimisation.

An observational study of end-tidal carbon dioxide trends in general anesthesia.

PURPOSE: Despite growing evidence supporting the potential benefits of higher end-tidal carbon dioxide (ETCO2) levels in surgical patients, there is still insufficient data to formulate guidelines for ideal intraoperative ETCO2 targets. As it is unclear which intraoperative ETCO2 levels are currently used and whether these levels have changed over time, we investigated the practice pattern using the Multicenter Perioperative Outcomes Group database. METHODS: This retrospective, observational, multicentre study included 317,445 adult patients who received general anesthesia for non-cardiothoracic procedures between January 2008 and September 2016. The primary outcome was a time-weighted average area-under-the-curve (TWA-AUC) for four ETCO2 thresholds (< 28, < 35, < 45, and > 45 mmHg). Additionally, a median ETCO2 was studied. A Kruskal-Wallis test was used to analyse differences between years. Random-effect multivariable logistic regression models were constructed to study variability. RESULTS: Both TWA-AUC and median ETCO2 showed a minimal increase in ETCO2 over time, with a median [interquartile range] ETCO2 of 33 [31.0-35.0] mmHg in 2008 and 35 [33.0-38.0] mmHg in 2016 (P <0.001). A large inter-hospital and inter-provider variability in ETCO2 were observed after adjustment for patient characteristics, ventilation parameters, and intraoperative blood pressure (intraclass correlation coefficient 0.36; 95% confidence interval, 0.18 to 0.58). CONCLUSIONS: Between 2008 and 2016, intraoperative ETCO2 values did not change in a clinically important manner. Interestingly, we found a large inter-hospital and inter-provider variability in ETCO2 throughout the study period, possibly indicating a broad range of tolerance for ETCO2, or a lack of evidence to support a specific targeted range. Clinical outcomes were not assessed in this study and they should be the focus of future research.

RéSUMé: OBJECTIF: Malgré une accumulation de données probantes suggérant des avantages de taux plus élevés de dioxyde de carbone en fin d'expiration (ETCO2) chez les patients chirurgicaux, nous ne disposons pas encore d'assez de données pour formuler des lignes directrices sur les cibles peropératoires idéales de l'ETCO2. Comme nous ne savons effectivement pas avec certitude quels taux peropératoires d'ETCO2 sont actuellement utilisés et si ces taux ont changé au fil du temps, nous avons étudié l'évolution de la pratique en utilisant la base de données du MPOG (Multicenter Perioperative Outcomes Group). MéTHODES: Cette étude multicentrique rétrospective observationnelle a inclus 317 445 patients adultes ayant reçu une anesthésie générale pour des procédures non cardiothoraciques entre janvier 2008 et septembre 2016. Le critère d'évaluation principal était une aire sous la courbe moyenne pondérée en fonction du temps (ASC-mT) pour quatre seuils d'ETCO2 (< 28, < 35, < 45 et > 45 mmHg). De plus, une ETCO2 médiane a été étudiée. Un test de Kruskal-Wallis a permis d'analyser les différences entre les années. Des modèles de régression logistique multifactorielle à effet aléatoire ont été construits pour étudier la variabilité. RéSULTATS: L'ASC-mT et l'ETCO2 médiane ont montré une augmentation minime de l'ETCO2 au fil du temps, avec une valeur médiane [plage interquartile] de l'ETCO2 de 33 [31,0 à 35,0] mmHg en 2008 et 35 [33,0 à 38,0] mmHg en 2016 (P < 0,001). Une grande variabilité entre les hôpitaux et prestataires de l'ETCO2 a été observée après ajustement pour les caractéristiques des patients, les paramètres de ventilation et la pression artérielle peropératoire (coefficient de corrélation intracatégorie : 0,36; intervalle de confiance à 95 % : 0,18 à 0,58). CONCLUSIONS: Entre 2008 et 2016, les valeurs peropératoires de l'ETCO2 n'ont pas varié d'une manière importante sur le plan clinique. Il est intéressant de noter que nous avons trouvé une grande variabilité de l'ETCO2 entre hôpitaux et prestataires tout au long de la période d'étude témoignant peut-être d'une vaste plage de tolérance de l'ETCO2 ou d'un manque de données probantes pour soutenir une valeur cible spécifique. L'évolution clinique n'a pas été analysée au cours de cette étude et elle devra être le centre d'intérêt de futures recherches.

Effect of cytomegalovirus reactivation on the time course of systemic host response biomarkers in previously immunocompetent critically ill patients with sepsis: a matched cohort study.

BACKGROUND: Cytomegalovirus (CMV) reactivation in previously immunocompetent critically ill patients is associated with increased mortality, which has been hypothesized to result from virus-induced immunomodulation. Therefore, we studied the effects of CMV reactivation on the temporal course of host response biomarkers in patients with sepsis. METHODS: In this matched cohort study, each sepsis patient developing CMV reactivation between day 3 and 17 (CMV+) was compared with one CMV seropositive patient without reactivation (CMVs+) and one CMV seronegative patient (CMVs-). CMV serostatus and plasma loads were determined by enzyme-linked immunoassays and real-time polymerase chain reaction, respectively. Systemic interleukin-6 (IL-6), IL-8, IL-18, interferon-gamma-induced protein-10 (IP-10), neutrophilic elastase, IL-1 receptor antagonist (RA), and IL-10 were measured at five time points by multiplex immunoassay. The effects of CMV reactivation on sequential concentrations of these biomarkers were assessed in multivariable mixed models. RESULTS: Among 64 CMV+ patients, 45 could be matched to CMVs+ or CMVs- controls or both. The two baseline characteristics and host response biomarker levels at viremia onset were similar between groups. CMV+ patients had increased IP-10 on day 7 after viremia onset (symmetric percentage difference +44% versus -15% when compared with CMVs+ and +37% versus +4% when compared with CMVs-) and decreased IL-1RA (-41% versus 0% and -49% versus +10%, respectively). However, multivariable analyses did not show an independent association between CMV reactivation and time trends of IL-6, IP-10, IL-10, or IL-1RA. CONCLUSION: CMV reactivation was not independently associated with changes in the temporal trends of host response biomarkers in comparison with non-reactivating patients. Therefore, these markers should not be used as surrogate clinical endpoints for interventional studies evaluating anti-CMV therapy.

Joint management format at the mixed-surgical intermediate care unit: an interrupted time series analysis.

BACKGROUND: The management format of the mixed-surgical intermediate care unit (IMCU) affects its performance. A format of combined supervision of surgeons with additional critical care certifications and admitting specialists, named the "joint format", may herein be a promising new model of specialized critical care. This study aims to assess the performance of the joint management format. METHODS: This observational cohort study compared three IMCU management formats at the stand-alone, mixed-surgical IMCU of a tertiary referral hospital using interrupted time series analyses. All admissions from 2001 until 2015 were included. Predetermined criteria for performance (utilization, efficiency, and safety) were applied to three different management format periods: open (2001-2006), closed (2006-2011), and joint (2011-2015) formats. RESULTS: A total of 8894 admissions were analyzed. In terms of case load (utilization), there was an overall increase in the number of surgical patients (0.25%/year) (p<0.001), age (0.38/year) (p<0.001), and readmissions from the ward (0.16%/year) (p<0.001) and from the intensive care unit (ICU) (0.17%/year) (p=0.014). In terms of efficiency, the admission duration decreased (1.58 hours/year) (p<0.001). Transfer to the ICU within 24 hours, readmission within 24 hours from the ward, and unplanned mortality (eg, safety) did not change over time. DISCUSSION: At a time of increasingly complex case load, the joint format at the mixed-surgical IMCU is an efficient and safe management format in which the admitting specialist continues to provide specialized care. Specialty-specific supervision at IMCUs is a safe option which should be considered in healthcare policy decisions. LEVEL OF EVIDENCE: Level IV.

Optimizing critical care of the trauma patient at the intermediate care unit: a cost-efficient approach.

BACKGROUND: The aim of this study was to describe the case load, safety, and cost savings of critical care of the trauma patient provided at the surgical intermediate care unit (IMCU). METHODS: This cohort study included all trauma admissions between January 1, 2011 and January 7, 2015 at the general intensive care unit (ICU), stand-alone neuro(surgical) IMCU, and stand-alone (trauma) surgical IMCU. Trauma mechanism, Abbreviated Injury Scale score and Injury Severity Score (ISS), vital signs, laboratory parameters, admission duration, intubation duration, ICU transfer, and in-hospital mortality were prospectively collected. Hypothetical cost savings were calculated using the fixed cost price per IMCU (US$1500) and ICU (US$2500) admission day. RESULTS: A total of 1320 admissions were included, 675 (51.1%) at the IMCU and 645 (48.9%) at the ICU. Patients admitted at the IMCU had a median ISS of 17 (11, 22). Their median duration of admission was 32.8 hours (18.8, 62.5). At the IMCU, one patient died due to aneurogenic shock. A subsequent ICU transfer was required in 38 (5.6%) IMCU admissions. Of these transfers, four patients died due to neurological deterioration. At the ICU, the median ISS was 22 (14, 30). Nearly all (n=620, 96.3%) ICU trauma patients required mechanical ventilation. Expected total cost savings due to the presence of the IMCU were US$1 772 785. DISCUSSION: A substantial amount of trauma patients in need of critical care can safely be admitted at the IMCU, without the need for further mechanical ventilation. Thereby, the IMCU could fulfill an essential cost-saving role in the management of severely injured trauma patients. LEVEL OF EVIDENCE: Level IV.

Assessment of the intermediate care unit triage system.

BACKGROUND: An important critique with respect to the utilization of intermediate care units (IMCU) is that they potentially admit patients who would otherwise be cared for on the regular ward. This would lead to an undesired waste of critical care resources. This article aims to (1) describe the caseload at the IMCU and (2) to assess the triage system at the IMCU to determine potentially unnecessary admissions. METHODS: This cohort study included all admissions at the mixed-surgical IMCU from 2001 to 2015. The Therapeutic Intervention Scoring System-28 (TISS-28) was prospectively collected for all admissions to describe the caseload at the IMCU and to identify medical criteria for admission. These were combined with logistical criteria to assess the IMCU triage system. RESULTS: A total of 8816 admissions were included in the study. The average TISS-28 was 20.19 (95% CI 18.05 to 22.33), corresponding with 3.57 (95% CI 3.19 to 3.94) hours of direct patient-related work per patient per nursing shift. Over time, this increased by an average of 0.27 points/year (p<0.001). Of all admissions, 6539 (74.2%) were medically considered to be justly admitted, and 7093 (80.4%) were logistically considered to be justly admitted. With these criteria combined, a total of 8324 (94.4%) were correctly admitted. DISCUSSION: Most admissions to the IMCU are medically and/or logistically necessary, as the majority of admitted patients demand a higher level of nursing care than available on the general ward. Continuous triage is thereby essential. These findings support further utilization of the IMCU in our current healthcare system and has important implications for IMCU-related management decisions. LEVEL OF EVIDENCE: Level VI.