Postoperative Staphylococcus aureus Infections in Patients With and Without Preoperative Colonization.

Importance: Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data on the incidence of and etiologic factors for these infections are needed to support the development of improved preventive strategies. Objectives: To assess the occurrence of postoperative S aureus SSIs and BSIs and quantify its association with patient-related and contextual factors. Design, Setting, and Participants: This multicenter cohort study assessed surgical patients at 33 hospitals in 10 European countries who were recruited between December 16, 2016, and September 30, 2019 (follow-up through December 30, 2019). Enrolled patients were actively followed up for up to 90 days after surgery to assess the occurrence of S aureus SSIs and BSIs. Data analysis was performed between November 20, 2020, and April 21, 2022. All patients were 18 years or older and had undergone 11 different types of surgical procedures. They were screened for S aureus colonization in the nose, throat, and perineum within 30 days before surgery (source population). Both S aureus carriers and noncarriers were subsequently enrolled in a 2:1 ratio. Exposure: Preoperative S aureus colonization. Main Outcomes and Measures: The main outcome was cumulative incidence of S aureus SSIs and BSIs estimated for the source population, using weighted incidence calculation. The independent association of candidate variables was estimated using multivariable Cox proportional hazards regression models. Results: In total, 5004 patients (median [IQR] age, 66 [56-72] years; 2510 [50.2%] female) were enrolled in the study cohort; 3369 (67.3%) were S aureus carriers. One hundred patients developed S aureus SSIs or BSIs within 90 days after surgery. The weighted cumulative incidence of S aureus SSIs or BSIs was 2.55% (95% CI, 2.05%-3.12%) for carriers and 0.52% (95% CI, 0.22%-0.91%) for noncarriers. Preoperative S aureus colonization (adjusted hazard ratio [AHR], 4.38; 95% CI, 2.19-8.76), having nonremovable implants (AHR, 2.00; 95% CI, 1.15-3.49), undergoing mastectomy (AHR, 5.13; 95% CI, 1.87-14.08) or neurosurgery (AHR, 2.47; 95% CI, 1.09-5.61) (compared with orthopedic surgery), and body mass index (AHR, 1.05; 95% CI, 1.01-1.08 per unit increase) were independently associated with S aureus SSIs and BSIs. Conclusions and Relevance: In this cohort study of surgical patients, S aureus carriage was associated with an increased risk of developing S aureus SSIs and BSIs. Both modifiable and nonmodifiable etiologic factors were associated with this risk and should be addressed in those at increased S aureus SSI and BSI risk.

Kidney Injury in Critically Ill Patients with COVID-19 - From Pathophysiological Mechanisms to a Personalized Therapeutic Model.

Acute kidney injury is a common complication of COVID-19, frequently fuelled by a complex interplay of factors. These include tubular injury and three primary drivers of cardiocirculatory instability: heart-lung interaction abnormalities, myocardial damage, and disturbances in fluid balance. Further complicating this dynamic, renal vulnerability to a "second-hit" injury, like a SARS-CoV-2 infection, is heightened by advanced age, chronic kidney disease, cardiovascular diseases, and diabetes mellitus. Moreover, the influence of chronic treatment protocols, which may constrain the compensatory intrarenal hemodynamic mechanisms, warrants equal consideration. COVID-19-associated acute kidney injury not only escalates mortality rates but also significantly affects long-term kidney function recovery, particularly in severe instances. Thus, the imperative lies in developing and applying therapeutic strategies capable of warding off acute kidney injury and decelerating the transition into chronic kidney disease after an acute event. This narrative review aims to proffer a flexible diagnostic and therapeutic strategy that recognizes the multi-faceted nature of COVID-19-associated acute kidney injury in critically ill patients and underlines the crucial role of a tailored, overarching hemodynamic and respiratory framework in managing this complex clinical condition.

The COVID-19 Vaccination Coverage in ICU Patients with Severe COVID-19 Infection in a Country with Low Vaccination Coverage-A National Retrospective Analysis.

BACKGROUND: Romania is one of the European countries with low COVID-19 vaccination coverage. The main goal of this study was to describe the COVID-19 vaccination status in patients admitted to Romanian ICUs with a severe COVID-19 infection. The study describes the patients' characteristics according to their vaccination status and evaluates the association between vaccination status and ICU mortality. METHODS: This retrospective, observational, multicenter study included patients with confirmed vaccination status admitted to Romanian ICUs from January 2021 to March 2022. RESULTS: Two thousand, two hundred and twenty-two patients with confirmed vaccination status were included. Five point one three percent of patients were vaccinated with two vaccine doses and one point seventeen percent of patients were vaccinated with one vaccine dose. The vaccinated patients showed a higher rate of comorbidities but had similar clinical characteristics at ICU admission and lower mortality rates compared to non-vaccinated patients. Vaccinated status and higher Glasgow Coma Scale at ICU admission were independently associated with ICU survival. Ischemic heart disease, chronic kidney disease, higher SOFA score at ICU admission and the need for mechanical ventilation in ICU were independently associated with ICU mortality. CONCLUSION: Lower rates of ICU admission were observed in fully vaccinated patients even in a country with low vaccination coverage. The ICU mortality was lower for fully vaccinated patients compared to non-vaccinated patients. The benefit of vaccination on ICU survival could be more important in patients with associated comorbidities.

A Brief Assessment of Patient Safety Culture in Anesthesia and Intensive Care Departments.

Due to the nature of their activity, anesthesia and critical care have generally well-developed patient safety cultures, which are linked to a greater level of incident awareness and reporting during clinical activity. In order to determine the status quo and identify and adopt, where appropriate, techniques and instruments for further improving patient safety, it is necessary to evaluate the culture and barriers in these departments. The main objective of our study was to assess patient safety culture in Romanian anesthesia and intensive care departments (AICDs), to pinpoint the areas that may need improvement, and to examine the correlation between the prevalence of adverse event reporting, as well as the level of self-reported patient safety culture. To determine how anesthesia and intensive care department staff perceived patient safety, the Hospital Survey on Patient Safety Culture (HSOPSC) was used in a translated Romanian version. In total, 1200 employees from 36 anesthesiology and intensive care departments across 32 hospitals in Romania received the questionnaire, representing 42.66% of all anesthesia and intensive care departments in the country. In 7 of the 12 examined dimensions, significant differences between tertiary and secondary hospitals were observed. Among all dimensions, the highest positive score was for "organizational learning and continuous development". In general, our study revealed a positive view on patient safety in anesthesia and intensive care departments. Further studies are required to determine a threshold of the level of culture development.

Veno-venous extracorporeal membrane oxygenation, cytokine removal and continuous renal replacement therapy in a severe burn adult patient.

Acute respiratory distress syndrome (ARDS) can develop early in burn patients with inhalation injury in the presence of cytokine storm and the proinflammatory response can be a supplemental factor for ARDS aggravation. We report the case of a 41-years old male with 25% total body surface area deep partial thickness burns to upper body extremity and grade II inhalational injury who developed severe ARDS, nosocomial pneumonia, and septic shock. Veno-venous extracorporeal membrane oxygenation (VV ECMO) and continuous renal replacement therapy (CRRT) with hemoadsorption were successfully used at different moments to overcome critical situations. Although debatable, the use of ECMO in burn patients with severe ARDS could be considered when conventional treatment fails. The use of CRRT combined with hemoadsorption may limit the proinflammatory response sustained by the combination between major burn, ECMO and sepsis.

Clinical characteristics and factors associated with ICU mortality during the first year of the SARS-Cov-2 pandemic in Romania: A prospective, cohort, multicentre study of 9000 patients.

BACKGROUND: The epidemiology of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be different worldwide. Despite similarities in medicine quality and formation, there are also significant differences concerning healthcare and ICU organisation, staffing, financial resources and population compliance and adherence. Large cohort data of critically ill patients from Central and Eastern Europe are also lacking. OBJECTIVES: The study objectives were to describe the clinical characteristics of patients admitted to Romanian ICUs with SARS-CoV-2 infection and to identify the factors associated with ICU mortality. DESIGN: Prospective, cohort, observational study. SETTING: National recruitment, multicentre study, between March 2020 to March 2021. PATIENTS: All patients with SARS-CoV-2 infection admitted to Romanian ICUs were eligible. There were no exclusion criteria. INTERVENTION: None. MAIN OUTCOME MEASURE: ICU mortality. RESULTS: The statistical analysis included 9058 patients with definitive ICU outcome. The multivariable mixed effects logistic regression model found that age [odds ratio (OR) 1.27; 95% confidence interval (CI), 1.23 to 1.31], male gender (OR 1.21; 95% CI 1.05 to 1.4), medical history of neoplasia (OR 1.74; 95% CI, 1.36 to 2.22), chronic kidney disease (OR 1.54; 95% CI, 1.27 to 1.88), type II diabetes (OR 1.23; 95% CI, 1.06 to 1.43), chronic heart failure (OR 1.24; 95% CI, 1.03 to 1.49), dyspnoea (OR 1.3; 95% CI, 1.1 to 1.5), SpO2 less than 90% (OR 3; 95% CI, 2.5 to 3.5), admission SOFA score (OR 1.07; 95% CI, 1.05 to 1.09), acute respiratory distress syndrome (ARDS) on ICU admission (OR 1.35; 95% CI, 1.1 to 1.63) and the need for noninvasive (OR 1.8, 95% CI, 1.5 to 1.22) or invasive ventilation (OR 28; 95% CI, 22 to 35) and neuromuscular blockade (OR 3.5; 95% CI, 2.6 to 4.8), were associated with larger ICU mortality.Higher GCS on admission (OR 0.81; 95% CI, 0.79 to 0.83), treatment with hydroxychloroquine (OR 0.78; 95% CI, 0.64 to 0.95) and tocilizumab (OR 0.58; 95% CI, 0.48 to 0.71) were inversely associated with ICU mortality. CONCLUSION: The SARS-CoV-2 critically ill Romanian patients share common personal and clinical characteristics with published European cohorts. Public health measures and vaccination campaign should focus on patients at risk.

Perioperative trajectory of plasma viscosity: A prospective, observational, exploratory study in cardiac surgery.

OBJECTIVE: Plasma viscosity is one of the critical factors that regulate microcirculatory flow but has received scant research attention. The main objective of this study was to evaluate plasma viscosity in cardiac surgery with respect to perioperative trajectory, main determinants, and impact on outcome. METHODS: Prospective, single center, observational study, including 50 adult patients undergoing cardiac surgery with cardiopulmonary bypass between February 1, 2020 and May 31, 2021. Clinical perioperative characteristics, short term outcome, standard blood analysis, plasma viscosity, total proteins, and fibrinogen concentrations were recorded at 10 distinct time points during the first perioperative week. RESULTS: The longitudinal analysis showed that plasma viscosity is strongly influenced by proteins and measurement time points. Plasma viscosity showed a coefficient of variation of 11.3 ± 1.08 for EDTA and 12.1 ± 2.1 for citrate, similarly to total proteins and hemoglobin, but significantly lower than fibrinogen (p < .001). Plasma viscosity had lower percentage changes compared to hemoglobin (RANOVA, p < .001), fibrinogen (RANOVA, p < .001), and total proteins (RANOVA, p < .001). The main determinant of plasma viscosity was protein concentrations. No association with outcome was found, but the study may have been underpowered to detect it. CONCLUSION: Plasma viscosity had a low coefficient of variation and low perioperative changes, suggesting tight regulation. Studies linking plasma viscosity with outcome would require large patient cohorts.

Outcomes of COVID-19 Critically Ill Extremely Elderly Patients: Analysis of a Large, National, Observational Cohort.

BACKGROUND: During the COVID-19 pandemic, resource allocation became a major problem in globally overwhelmed ICUs. The main goal of this study was to describe the clinical characteristics of the very elderly patients (aged ≥ 80 years) with COVID-19 admitted in Romanian ICUs. The study objectives were to evaluate and determine the factors associated with ICU mortality. METHODS: We designed a national, multicentric, observational platform with prospective enrolment. This study included patients aged ≥ 80 years admitted in Romanian ICUs with SARS-CoV-2 infection from March 2020 to December 2021. RESULTS: We included 1666 patients with a median age of 83 years and 78% ICU mortality. Male sex, dyspnoea, lower Glasgow Coma Scale and lower SpO2 at ICU admission, the need for mechanical ventilation (MV), and corticosteroid use were independently associated with mortality. A total of 886/1666 (53%) elderly patients underwent invasive mechanical ventilation, with a mortality of 97%. The age impact on mortality was confirmed by a 1:1 propensity matching with less elderly ICU patients. CONCLUSION: In extremely elderly patients with COVID-19 admitted in the ICU, mortality is high, particularly when requiring MV. Therapy should be directed towards the optimization of less invasive ventilatory methods and the use of MV and corticosteroids only in highly selected patients.

Hemodynamic Monitoring in Sepsis-A Conceptual Framework of Macro- and Microcirculatory Alterations.

Circulatory failure in sepsis is common and places a considerable burden on healthcare systems. It is associated with an increased likelihood of mortality, and timely recognition is a prerequisite to ensure optimum results. While there is consensus that aggressive source control, adequate antimicrobial therapy and hemodynamic management constitute crucial determinants of outcome, discussion remains about the best way to achieve each of these core principles. Sound cardiovascular support rests on tailored fluid resuscitation and vasopressor therapy. To this end, an overarching framework to improve cardiovascular dynamics has been a recurring theme in modern critical care. The object of this review is to examine the nature of one such framework that acknowledges the growing importance of adaptive hemodynamic support combining macro- and microhemodynamic variables to produce adequate tissue perfusion.

Ultrasound-Guided Regional Anesthesia-Current Strategies for Enhanced Recovery after Cardiac Surgery.

With the advent of fast-track pathways after cardiac surgery, there has been a renewed interest in regional anesthesia due to its opioid-sparing effect. This paradigm shift, looking to improve resource allocation efficiency and hasten postoperative extubation and mobilization, has been pursued by nearly every specialty area in surgery. Safety concerns regarding the use of classical neuraxial techniques in anticoagulated patients have tempered the application of regional anesthesia in cardiac surgery. Recently described ultrasound-guided thoracic wall blocks have emerged as valuable alternatives to epidurals and landmark-driven paravertebral and intercostal blocks. These novel procedures enable safe, effective, opioid-free pain control. Although experience within this field is still at an early stage, available evidence indicates that their use is poised to grow and may become integral to enhanced recovery pathways for cardiac surgery patients.

Interchangeability of cardiac output measurements between non-invasive photoplethysmography and bolus thermodilution: A systematic review and individual patient data meta-analysis.

BACKGROUND: Continuous non-invasive cardiac output devices using digital photoplethysmography (PPG) are widely available for bedside use, but their interchangeability with reference methods has not yet been evaluated in a systematic review and patient data meta-analysis. METHODS: A systematic review and meta-analysis of studies comparing non-invasive cardiac output monitoring using PPG with the invasive bolus thermodilution method was performed. With ethical approval, all published studies from the PUBMED, Embase, Scopus, Web of Science, and Google Scholar databases from January 1, 2010 to January 1, 2018 were included. From these analysed studies, individual patient data were interpreted using the interchangeability methods for both absolute values and changes in cardiac output measurements. RESULTS: Ten studies comparing PPG and bolus thermodilution in the operating room and intensive care settings were included. The interchangeability rate (95% CI) was 37% (24-48) (n=1350 pairs of measurements). The interchangeability rate was poorer with the CNAP device (CNSystems, Graz, Austria) [18% (17-20)] than with the Clearsight (Edwards Lifesciences, Irvine, CA) device [33% (31-34), P<0.0001], for patients receiving norepinephrine [19% (17-20) vs. 33% (32-34), P<0.0001], and for patients with low mean arterial pressure (<65mmHg) [26% (23-29) vs. 30% (29-31), P<0.0001]. Among the 1009 comparisons of the changes in cardiac output between both methods, 561 (56%) were interpretable with a trend interchangeability rate at 24% (12-36). CONCLUSIONS: Cardiac output measurements using PPG were not interchangeable with bolus thermodilution in regard to both absolute values and changes in cardiac output measurements, and should be used with caution in clinical practice. TRIAL REGISTRATION: PROSPERO ID CRD42018089513.

The value of a superior vena cava collapsibility index measured with a miniaturized transoesophageal monoplane continuous echocardiography probe to predict fluid responsiveness compared to stroke volume variations in open major vascular surgery: a prospective cohort study.

Superior vena cava collapsibility index (SVC-CI) and stroke volume variation (SVV) have been shown to predict fluid responsiveness. SVC-CI has been validated only with conventional transoesophageal echocardiography (TEE) in the SVC long axis, on the basis of SVC diameter variations, but not in the SVC short axis or by SVC area variations. SVV was not previously tested in vascular surgery patients. Forty consecutive adult patients undergoing open major vascular surgical procedures received 266 intraoperative volume loading tests (VLTs), with 500 ml of gelatine over 10 min. The hSVC-CI was measured using a miniaturized transoesophageal echocardiography probe (hTEE). The SVV and cardiac index (CI) were measured using Vigileo-FloTrac technology. VLTs were considered 'positive' (≥ 11% increase in CI) or 'negative' (< 11% increase in CI). We compared SVV and hSVC-CI measurements in the SVC short axis to predict fluid responsiveness. Areas under the receiver operating characteristic curves for hSVC-CI and SVV were not significantly different (P = 0.56), and both showed good predictivity at values of 0.92 (P < 0.001) and 0.89 (P < 0.001), respectively. The cutoff values for hSVC-CI and SVV were 37% (sensitivity 90%, specificity of 83%) and 15% (sensitivity 78%, specificity of 100%), respectively. Our study validated the value of the SVC-CI measured as area variations in the SVC short axis to predict fluid responsiveness in anesthetized patients. An hTEE probe was used to monitor and measure the hSVC-CI but conventional TEE may also offer this new dynamic parameter. In our cohort of significant preoperative hypovolemic patients undergoing major open vascular surgery, hSVC-CI and SVV cutoff values of 37% and 15%, respectively, predicted fluid responsiveness with good accuracy.

Continuous Noninvasive Hemoglobin Monitoring Reflects the Development of Acute Hemodilution After Consecutive Fluid Challenges.

BACKGROUND: Consecutive fluid challenges (FCs) are frequently administered to maximize the stroke volume (SV) as part of a goal-directed therapy (GDT) strategy. However, fluid administration may also cause acute hemodilution that might lead to an actual paradoxical decrease in oxygen delivery (DO2). The aim of this study was to examine whether continuous noninvasive hemoglobin (SpHb) monitoring can be used to detect the development of acute hemodilution after graded fluid administration. METHODS: In 40 patients who underwent major vascular or gastrointestinal surgery, an FC, consisting of 250 mL colloid solution, was administered. When the SV increased by ≥10%, the FC was repeated up to a maximum of 3 times. Laboratory-measured hemoglobin concentrations (BHb), SpHb, SV, cardiac output (CO), and DO2 values were recorded after each FC. RESULTS: All 40 patients received the first FC, 32 patients received the second FC, and 20 patients received the third FC (total of 750 mL). Out of the 92 administered FCs, only 55 (60%) caused an increase in SV ≥10% ("responders"). The first and the second FCs were associated with a significant increase in the mean CO and DO2, while the mean SpHb and BHb decreased significantly. However, the third and last FC was associated with no statistical difference in CO and SV, a further significant decrease in mean SpHb and BHb, and a significant decrease in DO2 in these patients. Compared to their baseline values (T0), BHb and SpHb decreased by a mean of 5.3% ± 4.9% and 4.4% ± 5.2%, respectively, after the first FC (T1; n = 40), by 9.7% ± 8.4% and 7.9% ± 6.9% after the second FC (T2; n = 32), and by 14.5% ± 6.2% and 14.6% ± 5.7% after the third FC (T3; n = 20). Concordance rates between the changes in SpHb and in BHb after the administration of 250, 500, and 750 mL colloids were 83%, 90%, and 100%, respectively. CONCLUSIONS: Fluid loading aimed at increasing the SV and the DO2 as part of GDT strategy is associated with acute significant decreases in both BHb and SpHb concentrations. When the administration of an FC is not followed by a significant increase (≥10%) in the SV, the DO2 decreases significantly due to the development of acute hemodilution. Continuous noninvasive monitoring of SpHb does not reflect accurately absolute BHb values, but may be reliably used to detect the development of acute hemodilution especially after the administration of at least 500 mL of colloids.

Burnout syndrome in the Anaesthesia and Intensive Care Unit.

BACKGROUND AND AIMS: This study aims to identify the extent to which Burnout syndrome is present among medical staff in the anaesthesia and intensive care units in Romania and if there are significant differences dependant on age or sex. METHODS: Maslach Burnout Inventory (MBI), structured in three dimensions: Emotional Exhaustion - 9 items (EE), Depersonalization - 6 items (D) and Reduction of personal achievement - 10 items (RPA), was used for the evaluation of Burnout Syndrome in 275 medical staff in anaesthesia and intensive care physician and nurses from departments in Romania. RESULTS: Burnout syndrome among medical staff with MBI had a total score of 68 and average scores for all syndrome categories. There were no statistically significant differences dependant on age and sex (p < 0.05, chi-squared test). The logistic regression has highlighted three elements that are risk factors, which belonged to the psycho-emotional sphere, communication abilities and the degree of organization and professional planning (item - I feel at the end of my rope, item - I do not communicate easily with people regardless of their social status and character, and item - I have professional disillusion). The risk factor with the most reliable range was the item "I feel at the end of my rope". CONCLUSION: The level of Burnout syndrome is medium regardless of sex or age category. Possibly, the concern of the ICU medical staff for the psycho-emotional life is not efficient, as well as for identifying/developing communication abilities. The association between risk factors for burnout syndrome and psychoemotional life development require further research.

The Diagnosis and Hemodynamic Monitoring of Circulatory Shock: Current and Future Trends.

Circulatory shock is a complex clinical syndrome encompassing a group of conditions that can arise from different etiologies and presented by several different hemodynamic patterns. If not corrected, cell dysfunction, irreversible multiple organ insufficiency, and death may occur. The four basic types of shock, hypovolemic, cardiogenic, obstructive and distributive, have features similar to that of hemodynamic shock. It is therefore essential, when monitoring hemodynamic shock, to making accurate clinical assessments which will guide and dictate appropriate management therapy. The European Society of Intensive Care has recently made recommendations for monitoring hemodynamic shock. The present paper discusses the issues raised in the new statements, including individualization of blood pressure targets, prediction of fluid responsiveness, and the use of echocardiography as the first means during the initial evaluation of circulatory shock. Also, the place of more invasive hemodynamic monitoring techniques and future trends in hemodynamic and metabolic monitoring in circulatory shock, will be debated.

Noninvasive continuous cardiac output by the Nexfin before and after preload-modifying maneuvers: a comparison with intermittent thermodilution cardiac output.

BACKGROUND: The Nexfin uses an uncalibrated pulse contour method for the continuous measurement of cardiac output (CO) in a totally noninvasive manner. Since the accuracy of pulse contour methods and their ability to track changes in CO have been repeatedly questioned, we have compared the CO measured by the Nexfin (NAPCO) with the CO measured by the pulmonary artery catheter (PACCO) in cardiosurgical patients before and after preload-modifying maneuvers. METHODS: Twenty-eight patients who underwent on-pump cardiac surgery, of whom 18 were receiving vasopressor and/or inotropic therapy, were studied during the first postoperative hours. Preload modification, in the form of either a fluid challenge or a passive leg raising maneuver, was done whenever clinically indicated, with PACCO and NAPCO being simultaneously measured before and after each intervention. RESULTS: A fluid challenge was administered to 22 patients, and the passive leg raising maneuver was performed in 6 patients. These interventions were repeated in 19 patients producing a total of 47 pairs of measurements. At baseline, mean (±SD) CO was 4.9 ± 1.1 and 5.0 ± 1.4 L·min(-1), for the PACCO and NAPCO, respectively, bias 0.1 ± 1.0, 95% prediction interval -2.5 to 2.4 L·min(-1), and 39% of error. After preload modification, the mean CO was 5.6 ± 1.3 and 5.6± 1.5 L·min(-1) for the PACCO and NAPCO, respectively, bias -0.0 ± 1.1, 95% prediction interval -2.6 to 2.7 L·min(-1), and 38% of error. The correlation coefficients (r) between the PACCO and NAPCO before and after preload modification were 0.71 (95% confidence interval [95% CI], 0.53-0.82) and 0.70 (95% CI, 0.52-0.82), respectively. Preload modification induced similar absolute changes in PACCO and NAPCO (r = 0.9, P < 0.0001). A 4-quadrant scatter plot showed a concordance rate of 100% (95% CI, 80.5%-100%) between the changes in NAPCO and PACCO. Polar plot analysis demonstrated a small polar angle and radial limits of agreement well below the 30° benchmark. The area under a receiver operating characteristic curve, testing the ability of Nexfin to detect an increase of ≥15% in PACCO, was 0.974 (95% CI, 0.93-0.99). CONCLUSIONS: Although the Nexfin has limited accuracy when compared with the pulmonary artery catheter, it can reliably track preload-induced changes in CO in stable patients after cardiac surgery in the presence of moderate vasopressor and inotropic therapy. This ability, combined with its total noninvasiveness, fast installation, and ease of use, make the Nexfin a suitable monitor for the perioperative continuous measurement of CO. The reliability of this monitor in tracking the CO when significant changes in peripheral resistance take place still needs to be established.

Haemodynamic effects, safety, and pharmacokinetics of human stresscopin in heart failure with reduced ejection fraction.

AIMS: Human stresscopin is a corticotropin-releasing factor (CRF) type 2 receptor (CRFR2) selective agonist and a member of the CRF peptide family. Stimulation of CRFR2 improves cardiac output and left ventricular ejection fraction (LVEF) in patients with stable heart failure (HF) with reduced LVEF. We examined the safety, pharmacokinetics, and effects on haemodynamics and serum biomarkers of intravenous human stresscopin acetate (JNJ-39588146) in patients with stable HF with LVEF ≤ 35% and cardiac index (CI) ≤ 2.5 L/min/m(2). METHODS AND RESULTS: Sixty-two patients with HF and LVEF ≤ 35% were instrumented with a pulmonary artery catheter and randomly assigned (ratio 3:1) to receive an intravenous infusion of JNJ-39588146 or placebo. The main study was an ascending dose study of three doses (5, 15, and 30 ng/kg/min) of study drug or placebo administered in sequential 1 h intervals (3 h total). Statistically significant increases in CI and reduction in systemic vascular resistance (SVR) were observed with both the 15 ng/kg/min (2 h time point) and 30 ng/kg/min (3 h time point) doses of JNJ-39588146 without significant changes in heart rate (HR) or systolic blood pressure (SBP). No statistically significant reductions in pulmonary capillary wedge pressure (PCWP) were seen with any dose tested in the primary analysis, although a trend towards reduction was seen. CONCLUSION: In HF patients with reduced LVEF and CI, ascending doses of JNJ-39588146 were associated with progressive increases in CI and reductions in SVR without significant effects on PCWP, HR, or SBP. TRIAL REGISTRATION: NCT01120210.