Cost-effectiveness of ECPR versus CCPR in OHCA; A pre-planned, trial-based economic evaluation.

INTRODUCTION: When out-of-hospital cardiac arrest (OHCA) becomes refractory, extracorporeal cardiopulmonary resuscitation (ECPR) is a potential option to restore circulation and improve the patient's outcome. However, ECPR requires specific materials and highly skilled personnel, and it is unclear whether increased survival and health-related quality of life (HRQOL) justify these costs. METHODS: This cost-effectiveness study was part of the INCEPTION study, a multicenter, pragmatic randomized trial comparing hospital-based ECPR to conventional CPR (CCPR) in patients with refractory OHCA in 10 cardiosurgical centers in the Netherlands. We analyzed healthcare costs in the first year and measured HRQOL using the EQ-5D-5L at 1, 3, 6, and 12 months. Incremental cost-effectiveness ratio's (ICER), cost-effectiveness planes, and acceptability curves were calculated. Sensitivity analyses were performed for per-protocol and as-treated subgroups as well as imputed productivity loss in deceased patients. RESULTS: In total 132 patients were enrolled: 62 in the CCPR and 70 in the ECPR group. The difference in mean costs after one year was €5,109 (95%CI -7,264-15,764). Mean QALY after one year was 0.15 in the ECPR group and 0.11 in the CCPR group, resulting in an ICER of €121,643 per additional QALY gained. The acceptability curve shows that at a willingness-to-pay threshold of €80.000, the probability of ECPR being cost-effective compared to CCPR is 36%. Sensitivity analysis showed increasing ICER in the per-protocol and as-treated groups and lower probabilities of acceptance. CONCLUSION: Hospital-based ECPR in refractory OHCA has a low probability of being cost-effective in a trial-based economic evaluation.

Inducing oscillations in positive end-expiratory pressure improves assessment of cerebrovascular pressure reactivity in patients with traumatic brain injury.

The cerebral pressure reactivity index (PRx), through intracranial pressure (ICP) measurements, informs clinicians about the cerebral autoregulation (CA) status in adult-sedated patients with traumatic brain injury (TBI). Using PRx in clinical practice is currently limited by variability over shorter monitoring periods. We applied an innovative method to reduce the PRx variability by ventilator-induced slow (1/min) positive end-expiratory pressure (PEEP) oscillations. We hypothesized that, as seen in a previous animal model, the PRx variability would be reduced by inducing slow arterial blood pressure (ABP) and ICP oscillations without other clinically relevant physiological changes. Patients with TBI were ventilated with a static PEEP for 30 min (PRx period) followed by a 30-min period of slow [1/min (0.0167 Hz)] +5 cmH2O PEEP oscillations (induced (iPRx period). Ten patients with TBI were included. No clinical monitoring was discontinued and no additional interventions were required during the iPRx period. The PRx variability [measured as the standard deviation (SD) of PRx] decreased significantly during the iPRx period from 0.25 (0.22-0.30) to 0.14 (0.09-0.17) (P = 0.006). There was a power increase around the induced frequency (1/min) for both ABP and ICP (P = 0.002). In conclusion, 1/min PEEP-induced oscillations reduced the PRx variability in patients with TBI with ICP levels <22 mmHg. No other clinically relevant physiological changes were observed. Reduced PRx variability might improve CA-guided perfusion management by reducing the time to find "optimal" perfusion pressure targets. Larger studies with prolonged periods of PEEP-induced oscillations are required to take it to routine use.NEW & NOTEWORTHY Cerebral autoregulation assessment requires sufficient slow arterial blood pressure (ABP) waves. However, spontaneous ABP waves may be insufficient for reliable cerebral autoregulation estimations. Therefore, we applied a ventilator "sigh-function" to generate positive end-expiratory pressure oscillations that induce slow ABP waves. This method demonstrated a reduced variability of the pressure reactivity index, commonly used as continuous cerebral autoregulation measure in a traumatic brain injury population.

Cerebral Autoregulation Assessment Using the Near Infrared Spectroscopy 'NIRS-Only' High Frequency Methodology in Critically Ill Patients: A Prospective Cross-Sectional Study.

Impairments in cerebral autoregulation (CA) are related to poor clinical outcome. Near infrared spectroscopy (NIRS) is a non-invasive technique applied to estimate CA. Our general purpose was to study the clinical feasibility of a previously published 'NIRS-only' CA methodology in a critically ill intensive care unit (ICU) population and determine its relationship with clinical outcome. Bilateral NIRS measurements were performed for 1-2 h. Data segments of ten-minutes were used to calculate transfer function analyses (TFA) CA estimates between high frequency oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) signals. The phase shift was corrected for serial time shifts. Criteria were defined to select TFA phase plot segments (segments) with 'high-pass filter' characteristics. In 54 patients, 490 out of 729 segments were automatically selected (67%). In 34 primary neurology patients the median (q1-q3) low frequency (LF) phase shift was higher in 19 survivors compared to 15 non-survivors (13° (6.3-35) versus 0.83° (-2.8-13), p = 0.0167). CA estimation using the NIRS-only methodology seems feasible in an ICU population using segment selection for more robust and consistent CA estimations. The 'NIRS-only' methodology needs further validation, but has the advantage of being non-invasive without the need for arterial blood pressure monitoring.

Serial Assessment of Myocardial Injury Markers in Mechanically Ventilated Patients With SARS-CoV-2 (from the Prospective MaastrICCht Cohort).

Myocardial injury in COVID-19 is associated with in-hospital mortality. However, the development of myocardial injury over time and whether myocardial injury in patients with COVID-19 at the intensive care unit is associated with outcome is unclear. This study prospectively investigates myocardial injury with serial measurements over the full course of intensive care unit admission in mechanically ventilated patients with COVID-19. As part of the prospective Maastricht Intensive Care COVID cohort, predefined myocardial injury markers, including high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and electrocardiographic characteristics were serially collected in mechanically ventilated patients with COVID-19. Linear mixed-effects regression was used to compare survivors with nonsurvivors, adjusting for gender, age, APACHE-II score, daily creatinine concentration, hypertension, diabetes mellitus, and obesity. In 90 patients, 57 (63%) were survivors and 33 (37%) nonsurvivors, and a total of 628 serial electrocardiograms, 1,565 hs-cTnT, and 1,559 NT-proBNP concentrations were assessed. Log-hs-cTnT was lower in survivors compared with nonsurvivors at day 1 (ß -0.93 [-1.37; -0.49], p <0.001) and did not change over time. Log-NT-proBNP did not differ at day 1 between both groups but decreased over time in the survivor group (ß -0.08 [-0.11; -0.04] p <0.001) compared with nonsurvivors. Many electrocardiographic abnormalities were present in the whole population, without significant differences between both groups. In conclusion, baseline hs-cTnT and change in NT-proBNP were strongly associated with mortality. Two-thirds of patients with COVID-19 showed electrocardiographic abnormalities. Our serial assessment suggests that myocardial injury is common in mechanically ventilated patients with COVID-19 and is associated with outcome.

Cost Analysis From a Randomized Comparison of Immediate Versus Delayed Angiography After Cardiac Arrest.

Background In patients with out-of-hospital cardiac arrest without ST-segment elevation, immediate coronary angiography did not improve clinical outcomes when compared with delayed angiography in the COACT (Coronary Angiography After Cardiac Arrest) trial. Whether 1 of the 2 strategies has benefits in terms of health care resource use and costs is currently unknown. We assess the health care resource use and costs in patients with out-of-hospital cardiac arrest. Methods and Results A total of 538 patients were randomly assigned to a strategy of either immediate or delayed coronary angiography. Detailed health care resource use and cost-prices were collected from the initial hospital episode. A generalized linear model and a gamma distribution were performed. Generic quality of life was measured with the RAND-36 and collected at 12-month follow-up. Overall total mean costs were similar between both groups (EUR 33 575±19 612 versus EUR 33 880±21 044; P=0.86). Generalized linear model: (ß, 0.991; 95% CI, 0.894-1.099; P=0.86). Mean procedural costs (coronary angiography and percutaneous coronary intervention, coronary artery bypass graft) were higher in the immediate angiography group (EUR 4384±3447 versus EUR 3028±4220; P<0.001). Costs concerning intensive care unit and ward stay did not show any significant difference. The RAND-36 questionnaire did not differ between both groups. Conclusions The mean total costs between patients with out-of-hospital cardiac arrest randomly assigned to an immediate angiography or a delayed invasive strategy were similar during the initial hospital stay. With respect to the higher invasive procedure costs in the immediate group, a strategy awaiting neurological recovery followed by coronary angiography and planned revascularization may be considered. Registration URL: https://trialregister.nl; Unique identifier: NL4857.

The PRICES statement: an ESICM expert consensus on methodology for conducting and reporting critical care echocardiography research studies.

PURPOSE: Echocardiography is a common tool for cardiac and hemodynamic assessments in critical care research. However, interpretation (and applications) of results and between-study comparisons are often difficult due to the lack of certain important details in the studies. PRICES (Preferred Reporting Items for Critical care Echocardiography Studies) is a project endorsed by the European Society of Intensive Care Medicine and conducted by the Echocardiography Working Group, aiming at producing recommendations for standardized reporting of critical care echocardiography (CCE) research studies. METHODS: The PRICE panel identified lists of clinical and echocardiographic parameters (the "items") deemed important in four main areas of CCE research: left ventricular systolic and diastolic functions, right ventricular function and fluid management. Each item was graded using a critical index (CI) that combined the relative importance of each item and the fraction of studies that did not report it, also taking experts' opinion into account. RESULTS: A list of items in each area that deemed essential for the proper interpretation and application of research results is recommended. Additional items which aid interpretation were also proposed. CONCLUSION: The PRICES recommendations reported in this document, as a checklist, represent an international consensus of experts as to which parameters and information should be included in the design of echocardiography research studies. PRICES recommendations provide guidance to scientists in the field of CCE with the objective of providing a recommended framework for reporting of CCE methodology and results.

Diagnostic accuracy of arterial and venous renal Doppler assessment for acute kidney injury in critically ill patients: A prospective study.

BACKGROUND AND PURPOSE: Renal Resistive Index (RRI) and Venous Impedance Index (VII) might be of additional value for diagnosing Acute Kidney Injury (AKI). The purpose of this study was to assess the diagnostic accuracy of RRI and VII for AKI. MATERIALS AND METHODS: In the prospective Simple Intensive Care Studies-II (NCT03577405), we measured RRI and VII in acutely admitted adult intensive care patients within 24 h of admission. AKI was defined by the Kidney Disease Improving Global Outcome (KDIGO) criteria. The primary outcome was persistent AKI, defined as non-resolved AKI on day three. We tested specificity, sensitivity and diagnostic accuracy of both RRI and VII for persistent AKI. RESULTS: In total, 371 patients were included of whom 123 patients (33%) had persistent AKI. RRI and VII did not differ between patients with and those without persistent AKI (p = .08 and p = .59). RRI had a moderate specificity (72%, 95%CI 66-78%) and low sensitivity (32%, 95%CI 24-41%) and VII had high sensitivity (93%, 95%CI 85-98%) and low specificity (11%, 95%CI 6-16%) for persistent AKI. Overall diagnostic accuracy of RRI and VII was moderate. CONCLUSIONS: In acutely admitted critically ill patients, measures of renal perfusion by renal ultrasound were not different between patients with and without AKI, and show limited diagnostic accuracy for AKI. Registered:NCT03577405.

Heart Rehabilitation in patients awaiting Open heart surgery targeting to prevent Complications and to improve Quality of life (Heart-ROCQ): study protocol for a prospective, randomised, open, blinded endpoint (PROBE) trial.

INTRODUCTION: The rising prevalence of modifiable risk factors (eg, obesity, hypertension and physical inactivity) is causing an increase in possible avoidable complications in patients undergoing cardiac surgery. This study aims to assess whether a combined preoperative and postoperative multidisciplinary cardiac rehabilitation (CR) programme (Heart-ROCQ programme) can improve functional status and reduce surgical complications, readmissions and major adverse cardiac events (MACE) as compared with standard care. METHODS AND ANALYSIS: Patients (n=350) are randomised to the Heart-ROCQ programme or standard care. The Heart-ROCQ programme consists of a preoperative optimisation phase while waiting for surgery (three times per week, minimum of 3 weeks), a postoperative inpatient phase (3 weeks) and an outpatient CR phase (two times per week, 4 weeks). Patients receive multidisciplinary treatment (eg, physical therapy, dietary advice, psychological sessions and smoking cessation). Standard care consists of 6 weeks of postsurgery outpatient CR with education and physical therapy (two times per week). The primary outcome is a composite weighted score of functional status, surgical complications, readmissions and MACE, and is evaluated by a blinded endpoint committee. The secondary outcomes are length of stay, physical and psychological functioning, lifestyle risk factors, and work participation. Finally, an economic evaluation is performed. Data are collected at six time points: at baseline (start of the waiting period), the day before surgery, at discharge from the hospital, and at 3, 7 and 12 months postsurgery. ETHICS AND DISSEMINATION: This study will be conducted according to the principles of the Declaration of Helsinki (V.8, October 2013). The protocol has been approved by the Medical Ethical Review Board of the UMCG (no 2016/464). Results of this study will be submitted to a peer-reviewed scientific journal and can be presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT02984449.

Cardiac rehabilitation for patients having cardiac surgery: a systematic review.

INTRODUCTION: Cardiac rehabilitation (CR) is recommended for all cardiac patients including patients after cardiac surgery. Since the effect of CR after cardiac surgery has not been well established yet, we conducted a systematic review on the effects of CR for patients after cardiac surgery compared to treatment as usual. EVIDENCE ACQUISITION: A systematic review of randomized clinical trials (RCTs), quasi-randomized and prospective observational studies in The Cochrane Library, PubMed/MEDLINE and EMBASE was undertaken until October 18th, 2017. Adults after any kind of cardiac surgery were included. Primary outcome was all-cause mortality, other outcomes were serious adverse events, health-related quality of life, work participation, functioning and costs/cost-effectiveness. Risk of bias was evaluated, and the quality of evidence was assessed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. EVIDENCE SYNTHESIS: Eighteen RCTs and 15 observational studies were included. Low risk of bias was only observed in one observational study. Meta-analysis of RCTs suggested no significant difference of CR compared to control on mortality (random-effects relative risk (RR) 0.93 (95% CI: 0.40-1.81), while observational studies suggested statistically significant beneficial effect associated with CR (random-effects RR=0.49, 95% CI: 0.35 - 0.68). CR did not significantly affect any of the other outcomes. Due to the limited data TSA could not be performed. CONCLUSIONS: The body of evidence does not allow us to reach any reliable conclusions about the effectiveness of CR following cardiac surgery. Future trials need to be conducted with low risks of bias and clearly defined outcomes.

Boussignac continuous positive airway pressure for the management of acute cardiogenic pulmonary edema: prospective study with a retrospective control group.

BACKGROUND: Continuous positive airway pressure (CPAP) treatment for acute cardiogenic pulmonary edema can have important benefits in acute cardiac care. However, coronary care units are usually not equipped and their personnel not adequately trained for applying CPAP with mechanical ventilators. Therefore we investigated in the coronary care unit setting the feasibility and outcome of the simple Boussignac mask-CPAP (BCPAP) system that does not need a mechanical ventilator. METHODS: BCPAP was introduced in a coronary care unit where staff had no CPAP experience. All consecutive patients transported to our hospital with acute cardiogenic pulmonary edema, a respiratory rate > 25 breaths/min and a peripheral arterial oxygen saturation of < 95% while receiving oxygen, were included in a prospective BCPAP group that was compared with a historical control group that received conventional treatment with oxygen alone. RESULTS: During the 2-year prospective BCPAP study period 108 patients were admitted with acute cardiogenic pulmonary edema. Eighty-four of these patients (78%) were treated at the coronary care unit of which 66 (61%) were treated with BCPAP. During the control period 66 patients were admitted over a 1-year period of whom 31 (47%) needed respiratory support in the intensive care unit. BCPAP treatment was associated with a reduced hospital length of stay and fewer transfers to the intensive care unit for intubation and mechanical ventilation. Overall estimated savings of approximately euro 3,800 per patient were achieved with the BCPAP strategy compared to conventional treatment. CONCLUSION: At the coronary care unit, BCPAP was feasible, medically effective, and cost-effective in the treatment of acute cardiogenic pulmonary edema. Endpoints included mortality, coronary care unit and hospital length of stay, need of ventilatory support, and cost (savings).