Wingless-related integration site (WNT) signaling is activated during the inflammatory response upon cardiac surgery: A translational study.

Objective: Cardiac surgery and the use of cardiopulmonary bypass initiate a systemic inflammatory response. Wingless-related integration site (WNT) signaling is part of the innate immunity and has been attributed a major role in the regulation of inflammation. In preclinical research, WNT-5a may sustain an inflammatory response and cause endothelial dysfunction. Our aim was to investigate WNT signaling after cardiac surgery and its association with postoperative inflammation (Clinicaltrials.gov, NCT04058496). Methods: In this prospective, single-center, observational study, 64 consecutive patients for coronary artery bypass grafting (CABG) ± valve surgery were assigned into three groups: off-pump CABG (n = 28), on-pump CABG (n = 16) and combined valve-CABG surgery (n = 20). Blood samples were acquired before surgery, at intensive care unit (ICU) admission and 4, 8, and 48 h thereafter. Plasma concentrations of WNT-5a and its antagonists Secreted frizzled-related protein 1 (sFRP-1), Secreted frizzled-related protein 5 (sFRP-5), and WNT inhibitory factor 1 (WIF-1) were determined by enzyme-linked immunosorbent assay. In addition, plasma concentrations of six inflammatory cytokines were measured by multiplex immunoassay. Parameters were analyzed for evolution of plasma concentration over time, interactions, intergroup differences, and association with clinical outcome parameters. Results: At baseline, WNT-5a, sFRP-1, and WIF-1 were present in a minimal concentration, while sFRP-5 was elevated. A higher baseline value of WNT-5a, sFRP-5, and WIF-1 resulted in higher subsequent values of the respective parameter. At ICU admission, WNT-5a and sFRP-5 reached their maximum and minimum value, respectively. WIF-1 decreased over time and was lowest 8 h after surgery. sFRP-1 changed minimally over time. While WNT-5a returned to the baseline within 48 h, sFRP-5 and WIF-1 did not reach their baseline value at 48 h. Of the investigated WNT system components, only WIF-1 partially reflected the severity of surgery. WNT-5a and WIF-1 had an impact on postoperative fluid balance and noradrenaline requirement. Conclusion: WNT-5a, sFRP-5, and WIF-1 are part of the systemic inflammatory response after cardiac surgery. WNT-5a peaks immediately after cardiac surgery and returns to baseline within 48 h, presumably modulated by its antagonist sFRP-5. Based on this translational study, WNT-5a antagonism may be further investigated to assess potentially beneficial effects in patients with a dysregulated inflammation after cardiac surgery.

Outcome, demography and resource utilization in ICU Patients with delirium and malignancy.

Delirium in the general intensive care unit (ICU) population is common, associated with adverse outcomes and well studied. However, knowledge on delirium in the increasing number of ICU patients with malignancy is scarce. The aim was to assess the frequency of delirium and its impact on resource utilizations and outcomes in ICU patients with malignancy. This retrospective, single-center longitudinal cohort study included all patients with malignancy admitted to ICUs of a University Hospital during one year. Delirium was diagnosed by an Intensive Care Delirium Screening Checklist (ICDSC) score ≥ 4. Of 488 ICU patients with malignancy, 176/488 (36%) developed delirium. Delirious patients were older (66 [55-72] vs. 61 [51-69] years, p = 0.001), had higher SAPS II (41 [27-68] vs. 24 [17-32], p < 0.001) and more frequently sepsis (26/176 [15%] vs. 6/312 [1.9%], p < 0.001) and/or shock (30/176 [6.1%] vs. 6/312 [1.9%], p < 0.001). In multivariate analysis, delirium was independently associated with lower discharge home (OR [95% CI] 0.37 [0.24-0.57], p < 0.001), longer ICU (HR [95% CI] 0.30 [0.23-0.37], p < 0.001) and hospital length of stay (HR [95% CI] 0.62 [0.50-0.77], p < 0.001), longer mechanical ventilation (HR [95% CI] 0.40 [0.28-0.57], p < 0.001), higher ICU nursing workload (B [95% CI] 1.92 [1.67-2.21], p < 0.001) and ICU (B [95% CI] 2.08 [1.81-2.38], p < 0.001) and total costs (B [95% CI] 1.44 [1.30-1.60], p < 0.001). However, delirium was not independently associated with in-hospital mortality (OR [95% CI] 2.26 [0.93-5.54], p = 0.074). In conclusion, delirium was a frequent complication in ICU patients with malignancy independently associated with high resource utilizations, however, it was not independently associated with in-hospital mortality.

Benralizumab in eosinophilic granulomatosis with polyangiitis complicated by Staphylococcus aureus sepsis.

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is an ANCA-associated small-vessels vasculitis characterized by hypereosinophilia and eosinophilic asthma. EGPA with life-threatening organ involvement, particularly cardiac and central nervous system (CNS), is a medical emergency requiring immediate immunosuppression. We describe a 58-year-old patient with a history of chronic rhinosinusitis and eosinophilic asthma, who presented with fever, hypereosinophilia and systemic inflammation. Diagnostic workup identified a cardiac mass, CNS vasculitis, CNS embolization and Staphylococcus aureus in blood cultures. Due to rapid normalization of blood cultures, the intracardiac mass was not considered as primarily infective. Active EGPA with cardiac and CNS involvement complicated by a secondary S. aureus sepsis was diagnosed. In order to not negatively impact antibacterial immunity in active EGPA, antibiotic therapy was combined with Benralizumab, which was well tolerated and EGPA resolved rapidly. Benralizumab could serve as a therapeutic option for eosinophil-mediated pathologies in severely ill patients where immunosuppressives are initially contraindicated.

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use.

Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use.

Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years.

Cardiovascular Safety of Clonidine and Dexmedetomidine in Critically Ill Patients after Cardiac Surgery.

PURPOSE: The aim of this retrospective study was to assess the haemodynamic adverse effects of clonidine and dexmedetomidine in critically ill patients after cardiac surgery. METHODS: 2769 patients were screened during the 30-month study period. Heart rate (HR), mean arterial pressure (MAP), and norepinephrine requirements were assessed 3-hourly during the first 12 hours of the continuous drug infusion. Results are given as median (interquartile range) or numbers (percentages). RESULTS: Patients receiving clonidine (n = 193) were younger (66 (57-73) vs 70 (63-77) years, p=0.003) and had a lower SAPS II (35 (27-48) vs 41 (31-54), p=0.008) compared with patients receiving dexmedetomidine (n = 141). At the start of the drug infusion, HR (90 (75-100) vs 90 (80-105) bpm, p=0.028), MAP (70 (65-80) vs 70 (65-75) mmHg, p=0.093), and norepinephrine (0.05 (0.00-0.11) vs 0.12 (0.03-0.19) mcg/kg/min, p < 0.001) were recorded in patients with clonidine and dexmedetomidine. Bradycardia (HR < 60 bpm) developed in 7.8% with clonidine and 5.7% with dexmedetomidine (p=0.51). Between baseline and 12 hours, norepinephrine remained stable in the clonidine group (0.00 (-0.04-0.02) mcg/kg/min) and decreased in the dexmedetomidine group (-0.03 (-0.10-0.02) mcg/kg/min, p=0.007). CONCLUSIONS: Dexmedetomidine and the low-cost drug clonidine can both be used safely in selected patients after cardiac surgery.

QTc prolongation after haloperidol administration in critically ill patients post cardiovascular surgery: A cohort study and review of the literature.

OBJECTIVE: From case reports, haloperidol administration has been associated with QTc prolongation, torsades de pointes, and sudden cardiac death. In a vulnerable population of critically ill patients after cardiac surgery, however, it is unclear whether haloperidol administration affects the QTc interval. Thus, the aim of this study is to explore the effect of haloperidol in low doses on this interval. METHOD: This retrospective cohort study was performed on a cardio-surgical intensive care unit (ICU), screened 2,216 patients and eventually included 68 patients with delirium managed with oral and intravenous haloperidol. In this retrospective analysis, electrocardiograms were taken prior and within 24 h after haloperidol administration. The effect of haloperidol on QTc was determined with a Person correlation, and inter-group differences were measured with new long QT comparisons. RESULTS: In total, 68 patients were included, the median age was 71 (64-79) years and predominantly male (77%). Haloperidol administration followed ICU admission by three days and the cumulative dose was 4 (2-9) mg. As a result, haloperidol administration did not affect the QTc (r = 0.144, p = 0.23). In total, 31% (21/68 patients) had a long QT before and 27.9% (19/68 patients) after haloperidol administration. Only 12% (8/68 patients) developed a newly onset long QT. These patients were not different in the route of administration, cumulative haloperidol doses, comorbidities, laboratory findings, or medications. SIGNIFICANCE OF RESULTS: These results indicated that low-dose intravenous haloperidol was safe and not clinically relevant for the development of a newly onset long QT syndrome or adverse outcomes and support recent findings inside and outside the ICU setting.

Delirium in the intensive care setting dependent on the Richmond Agitation and Sedation Scale (RASS): Inattention and visuo-spatial impairment as potential screening domains.

OBJECTIVE: In the intensive care setting, delirium is a common occurrence; however, the impact of the level of alertness has never been evaluated. Therefore, this study aimed to assess the delirium characteristics in the drowsy, as well as the alert and calm patient. METHOD: In this prospective cohort study, 225 intensive care patients with Richmond Agitation and Sedation Scale (RASS) scores of -1 - drowsy and 0 - alert and calm were evaluated with the Delirium Rating Scale-Revised-1998 (DRS-R-98) and the Diagnostic and Statistical Manual 4th edition text revision (DSM-IV-TR)-determined diagnosis of delirium. RESULTS: In total, 85 drowsy and 140 alert and calm patients were included. Crucial items for the correct identification of delirium were sleep-wake cycle disturbances, language abnormalities, thought process alterations, psychomotor retardation, disorientation, inattention, short- and long-term memory, as well as visuo-spatial impairment, and the temporal onset. Conversely, perceptual disturbances, delusions, affective lability, psychomotor agitation, or fluctuations were items, which identified delirium less correctly. Further, the severities of inattentiveness and visuo-spatial impairment were indicative of delirium in both alert- or calmness and drowsiness. SIGNIFICANCE OF RESULTS: The impairment in the cognitive domain, psychomotor retardation, and sleep-wake cycle disturbances correctly identified delirium irrespective of the level alertness. Further, inattentiveness and - to a lesser degree - visuo-spatial impairment could represent a specific marker for delirium in the intensive care setting meriting further evaluation.

Pulsatile arterial blood pressure mimicking aortic valve opening during continuous-flow LVAD support: a case report.

BACKGROUND: Left ventricular assist devices (LVAD) have become a common treatment option in advanced heart failure. Lack of aortic valve opening during left ventricular unloading is a common complication and associated with a worse outcome. Maintaining a minimum pulse pressure is an important goal during the early postoperative period after LVAD implantation since it is commonly seen as secure sign of aortic valve opening. AIMS/OBJECTIVE: We report a case of an LVAD-supported patient with early permanent closure of the aortic valve despite a pulse pressure > 15 mmHg at all times following LVAD implantation. We demonstrate how careful assessment of the invasive arterial blood pressure curve can indicate aortic valve closure irrespective of pulsatile blood flow. METHOD: A 69-year old male patient with terminal ischemic cardiomyopathy was referred for long-term mechanical circulatory support. Due to mild aortic regurgitation both an aortic bioprosthesis and a continuous-flow left ventricular assist device were implanted. Postoperative echocardiography documented a patent aortic bioprosthesis and an acceptable residual systolic left ventricular contractility. During invasive arterial blood pressure monitoring repetitive transient slight blood pressure decreases followed by slight blood pressure increases coincided with programmed LVAD flushing cycles. Permanent pulsatile flow with a pulse pressure of ≥15 mmHg conveyed systolic opening of the aortic valve. Echocardiography, however, proved early permanent aortic valve closure. In retrospect, transformation of the automated LVAD flushing cycles into visible changes of the arterial blood pressure curve during invasive blood pressure monitoring is indicative of ejection of the complete cardiac output through LVAD itself, and therefore an early clinical sign of aortic valve closure. DISCUSSION/CONCLUSION: We present this interesting didactic case to highlight caveats during the early postoperative period after LVAD implantation. Moreover, this case demonstrates that careful and differentiated observation of the arterial blood pressure waveform provides crucial information in this unique and growing patient population of continuous-flow LVAD support.

Screening for delirium with the Intensive Care Delirium Screening Checklist (ICDSC): Symptom profile and utility of individual items in the identification of delirium dependent on the level of sedation.

OBJECTIVE: The importance of the proper identification of delirium, with its high incidence and adversities in the intensive care setting, has been widely recognized. One common screening instrument is the Intensive Care Delirium Screening Checklist (ICDSC); however, the symptom profile and key features of delirium dependent on the level of sedation have not yet been evaluated. METHOD: In this prospective cohort study, the ICDSC was evaluated versus the Diagnostic and Statistical Manual, 4th edition, text revision, diagnosis of delirium set as standard with respect to the symptom profile, and correct identification of delirium. The aim of this study was to identify key features of delirium in the intensive care setting dependent on the Richmond Agitation and Sedation Scale levels of sedation: drowsiness versus alert and calmness.ResultThe 88 delirious patients of 225 were older, had more severe disease, and prolonged hospitalization. Irrespective of the level of sedation, delirium was correctly classified by items related to inattention, disorientation, psychomotor alterations, inappropriate speech or mood, and symptom fluctuation. In the drowsy patients, inattention reached substantial sensitivity and specificity, whereas psychomotor alterations and sleep-wake cycle disturbances were sensitive lacked specificity. The positive prediction was substantial across items, whereas the negative prediction was only moderate. In the alert and calm patient, the sensitivities were substantial for psychomotor alterations, sleep-wake cycle disturbances, and symptom fluctuations; however, these fluctuations were not specific. The positive prediction was moderate and the negative prediction substantial. Between the nondelirious drowsy and alert, the symptom profile was similar; however, drowsiness was associated with alterations in consciousness.Significance of resultsIn the clinical routine, irrespective of the level of sedation, delirium was characterized by the ICDSC items for inattention, disorientation, psychomotor alterations, inappropriate speech or mood and symptom fluctuation. Further, drowsiness caused altered levels of consciousness.

Use of Levosimendan in Intensive Care Unit Settings: An Opinion Paper.

Levosimendan is an inodilator that promotes cardiac contractility primarily through calcium sensitization of cardiac troponin C and vasodilatation via opening of adenosine triphosphate-sensitive potassium (KATP) channels in vascular smooth muscle cells; the drug also exerts organ-protective effects through a similar effect on mitochondrial KATP channels. This pharmacological profile identifies levosimendan as a drug that may have applications in a wide range of critical illness situations encountered in intensive care unit medicine: hemodynamic support in cardiogenic or septic shock; weaning from mechanical ventilation or from extracorporeal membrane oxygenation; and in the context of cardiorenal syndrome. This review, authored by experts from 9 European countries (Austria, Belgium, Czech republic, Finland, France, Germany, Italy, Sweden, and Switzerland), examines the clinical and experimental data for levosimendan in these situations and concludes that, in most instances, the evidence is encouraging, which is not the case with other cardioactive and vasoactive drugs routinely used in the intensive care unit. The size of the available studies is, however, limited and the data are in need of verification in larger controlled trials. Some proposals are offered for the aims and designs of these additional studies.

A hospital-wide evaluation of delirium prevalence and outcomes in acute care patients - a cohort study.

BACKGROUND: Delirium is a well-known complication in cardiac surgery and intensive care unit (ICU) patients. However, in many other settings its prevalence and clinical consequences are understudied. The aims of this study were: (1) To assess delirium prevalence in a large, diverse cohort of acute care patients classified as either at risk or not at risk for delirium; (2) To compare these two groups according to defined indicators; and (3) To compare delirious with non-delirious patients regarding hospital mortality, ICU and hospital length of stay, nursing hours and cost per case. METHODS: This cohort study was performed in a Swiss university hospital following implementation of a delirium management guideline. After excluding patients aged < 18 years or with a length of stay (LOS) < 1 day, 29'278 patients hospitalized in the study hospital in 2014 were included. Delirium period prevalence was calculated based on a Delirium Observation Scale (DOS) score ≥ 3 and / or Intensive Care Delirium Screening Checklist (ICDSC) scores ≥4. RESULTS: Of 10'906 patients admitted, DOS / ICDSC scores indicated delirium in 28.4%. Delirium was most prevalent (36.2-40.5%) in cardiac surgery, neurosurgery, trauma, radiotherapy and neurology patients. It was also common in geriatrics, internal medicine, visceral surgery, reconstructive plastic surgery and cranio-maxillo-facial surgery patients (prevalence 21.6-28.6%). In the unadjusted and adjusted models, delirious patients had a significantly higher risk of inpatient mortality, stayed significantly longer in the ICU and hospital, needed significantly more nursing hours and generated significantly higher costs per case. For the seven most common ICD-10 diagnoses, each diagnostic group's delirious patients had worse outcomes compared to those with no delirium. CONCLUSIONS: The results indicate a high number of patients at risk for delirium, with high delirium prevalence across all patient groups. Delirious patients showed significantly worse clinical outcomes and generated higher costs. Subgroup analyses highlighted striking variations in delirium period-prevalence across patient groups. Due to the high prevalence of delirium in patients treated in care centers for radiotherapy, visceral surgery, reconstructive plastic surgery, cranio-maxillofacial surgery and oral surgery, it is recommended to expand the current focus of delirium management to these patient groups.

Comparison of Levosimendan and Milrinone for ECLS Weaning in Patients After Cardiac Surgery-A Retrospective Before-and-After Study.

OBJECTIVES: Pharmacodynamics suggests that levosimendan might be a valuable inotrope for weaning from extracorporeal life support (ECLS). As there is a paucity of evidence regarding the effectiveness and safety of such an approach, the aim was to report the authors' experiences in ECLS weaning before and after the implementation of levosimendan in clinical practice. DESIGN: Retrospective before-and-after study. SETTING: Cardiac intensive care unit of a university hospital. PARTICIPANTS: A total of 64 patients under ECLS for postcardiotomy cardiac failure, who underwent an ECLS weaning trial. INTERVENTION: Group comparisons between patients treated with levosimendan and patients treated with milrinone were made with the Mann-Whitney U test or the Pearson chi-squared test. Results are given as median (interquartile range) or numbers (percentages). MEASUREMENTS AND MAIN RESULTS: Of 64 patients, 26 (41%) received levosimendan. Successful ECLS weaning was achieved in 24 (92%) and 30 patients (79%) in the levosimendan and milrinone group, respectively (p = 0.18). In the levosimendan group, fewer patients had an intra-aortic balloon pump for weaning (2 [7.7%] v 15 [40%], p = 0.008). The support with norepinephrine was similar in the levosimendan and milrinone groups at the time of ECLS removal (0.06 [0.01-0.11] v 0.07 [0.01-0.16] µg/kg/min, p = 0.64) and 24 hours later (0.06 [0.04-0.09] v 0.04 [0.00-0.09] µg/kg/min, p = 0.15). Twenty-eight days (9/26 (35%) v 14/35 (40%), p = 0.28) and 180 days (13/26 [50%] v 15/34 [44%], p = 0.80) mortalities after ECLS removal were similar in the levosimendan and the milrinone groups. CONCLUSION: Levosimendan enabled ECLS weaning without increasing norepinephrine requirements when compared to a control group receiving milrinone.

Screening for delirium with the Intensive Care Delirium Screening Checklist (ICDSC): a re-evaluation of the threshold for delirium.

BACKGROUND: With its high incidence and subsequent adverse consequences in the intensive care setting, several instruments have been developed to screen for and detect delirium. One of the more commonly used is the Intensive Care Delirium Screening Checklist (ICDSC); however, the optimal cut-off score indicating delirium has been debated. METHODS: In this prospective cohort study, the ICDSC threshold for delirium set at ≥3, ≥4, or ≥5 was compared with the DSM-IV-TR-determined diagnosis of delirium (used as standard), and with the Confusion Assessment Method for the ICU (CAM-ICU), with respect to their concurrent validity. RESULTS: In total, 289 patients were assessed, including 122 with delirium. The cut-off score of ≥4 had several shortcomings: although 90% of patients with delirium were correctly classified, 23% remained undetected. The agreement with the DSM-IV-TR diagnosis of delirium was only moderate (Cohen's κ 0.59) and the sensitivity was only 62%. In contrast, when the cut-off was ≥3, 83% of patients with delirium were correctly classified and only 14.5% remained undetected. The agreement with DSM-IV-TR was substantial (Cohen's κ 0.68) and the sensitivity increased to 83%. The benefit of setting the cut-off at ≥5 was not convincing: although 90% of patients with delirium were correctly classified, 30% remained undetected. The concurrent validity was only moderate (Cohen's κ 0.44), and the sensitivity reached only 44%. Changing the ICDSC cut-off score did not strengthen the moderate agreement with the CAM-ICU (Cohen's κ 0.45-0.56). CONCLUSION: In clinical routine, decreasing the ICDSC threshold for delirium to ≥3 increased the accuracy in detecting delirium at the cost of over-identification and is therefore recommended as the optimal threshold. Increasing the cut-off score to ≥5 decreased the concurrent validity and sensitivity; in addition, the under-detection of delirium was substantial.

Intra-operative events during cardiac surgery are risk factors for the development of delirium in the ICU.

BACKGROUND: Risk factors for delirium following cardiac surgery are incompletely understood. The aim of this study was to investigate whether intra-operative pathophysiological alterations and therapeutic interventions influence the risk of post-operative delirium. METHODS: This retrospective cohort study was performed in a 12-bed cardiosurgical intensive care unit (ICU) of a university hospital and included patients consecutively admitted after cardiac surgery during a 2-month period. The diagnosis of delirium was made clinically using validated scores. Comparisons between patients with and without delirium were performed with non-parametric tests. Logistic regression was applied to identify independent risk factors. Results are given as number (percent) or median (range). RESULTS: Of the 194 consecutive post-cardiac surgery patients, 50 (26 %) developed delirium during their ICU stay. Univariate analysis revealed that significant differences between patients with and without delirium occurred in the following intra-operative variables: duration of cardiopulmonary bypass (184 [72-299] vs 113 (37-717) minutes, p < 0.001), lowest mean arterial pressure (50 [30-70] vs 55 [30-75] mmHg, p = 0.004), lowest haemoglobin level (85 [56-133] vs 98 [53-150] g/L, p = 0.005), lowest body temperature (34.5 [24.4-37.2] vs 35.1 [23.9-37.2] °C, p = 0.035), highest noradrenaline support (0.11 [0.00-0.69] vs 0.07 [0.00-0.42] µg/kg/minute, p = 0.001), and frequency of red blood cell transfusions (18 [36 %] vs 26 [18 %], p = 0.018) and platelet transfusions (23 [46 %] vs 24 [17 %], p < 0.001). Only platelet transfusions remained an independent risk factor in the multivariate analysis (p < 0.001). CONCLUSIONS: In patients undergoing cardiac surgery, various intra-operative events, such as transfusion of platelets, were risk factors for the development of a post-operative delirium in the ICU. Further research is needed to unravel the underlying mechanisms.

Shock Management for Cardio-surgical Intensive Care Unit Patient: The Silver Days.

Shock in cardio-surgical intensive care unit (ICU) patients requires prompt identification of the underlying condition and timely therapeutic interventions. Management during the first 6 hours, also referred to as "the golden hours", is of paramount importance to reverse the shock state and improve the patient's outcome. The authors have previously described a state-of-the-art diagnostic work-up and discussed how to optimise preload, vascular tone, contractility, heart rate and oxygen delivery during this phase. Ideally, shock can be reversed during this initial period. However, some patients might have developed multiple organ dysfunction, which persists beyond the first 6 hours despite the early haemodynamic treatment goals having been accomplished. This period, also referred to as "the silver days", is the focus of this review. The authors discuss how to reduce vasopressor load and how to minimise adrenergic stress by using alternative inotropes, extracorporeal life-support and short acting beta-blockers. The review incorporates data on fluid weaning, safe ventilation, daily interruption of sedation, delirium management and early rehabilitation. It includes practical recommendations in areas where the evidence is scarce or controversial. Although the focus is on cardio-surgery ICU patients, most of the considerations apply to critical ill patients in general.

Pancreatic stone protein predicts postoperative infection in cardiac surgery patients irrespective of cardiopulmonary bypass or surgical technique.

INTRODUCTION: We investigated the role of pancreatic stone protein (PSP) in predicting the occurrence of infection in the postoperative course of cardiac surgery patients. Several biomarkers indicating the presence of inflammation and infection are available in the clinical routine; yet, their utility in the postoperative course of patients following cardiac surgery remains uncertain. Moreover, cardiopulmonary bypass, also referred to as "on-pump surgery", increases the susceptibility to an exaggerated inflammatory state. However, the impact of such extracorporeal circulation on circulating PSP levels remains poorly understood. METHODS: In a prospective cohort of unselected patients undergoing cardiac surgery, we set out to elucidate the diagnostic accuracy of serum PSP levels as opposed to canonical biomarkers (CRP, WBC) of inflammation to discriminate between the presence of infection and surgical trauma,. In addition, we investigated whether the biomarkers were influenced by the surgical technique employed, i.e. on-pump vs. off-pump and minimally invasive surgery vs. sternotomy. Levels of circulating PSP and routine inflammatory biomarkers (CRP, WBC) were measured in samples taken from 120 patients at baseline as well as at postoperative day 1-3. RESULTS: Univariate analysis showed that among the biomarkers investigated, only PSP levels had discriminatory power to differentiate infection from surgical trauma in the postoperative course of the entire cohort of patients following cardiac surgery. With regard to cardiac surgical interventions, there was no significant association between the absence or presence of extracorporeal circulation and PSP levels. However, there was a significant difference in the slope of the rise of postoperative PSP between minimally invasive surgery as opposed to patients subjected to sternotomy. CONCLUSION: In an unselected population of cardiac surgery patients, post-operative serum PSP levels were significantly associated with the presence of infection in both the on-pump and off-pump setting. Of note, the surgical technique employed (sternotomy vs. minimally invasive approach) had a significant impact on postoperative PSP levels.