T-cell recovery and evidence of persistent immune activation 12 months after severe COVID-19.

BACKGROUND: T-cell lymphopenia and functional impairment is a hallmark of severe acute coronavirus disease 2019 (COVID-19). How T-cell numbers and function evolve at later timepoints after clinical recovery remains poorly investigated. METHODS: We prospectively enrolled and longitudinally sampled 173 individuals with asymptomatic to critical COVID-19 and analyzed phenotypic and functional characteristics of T cells using flow cytometry, 40-parameter mass cytometry, targeted proteomics, and functional assays. RESULTS: The extensive T-cell lymphopenia observed particularly in patients with severe COVID-19 during acute infection had recovered 6 months after infection, which was accompanied by a normalization of functional T-cell responses to common viral antigens. We detected persisting CD4+ and CD8+ T-cell activation up to 12 months after infection, in patients with mild and severe COVID-19, as measured by increased HLA-DR and CD38 expression on these cells. Persistent T-cell activation after COVID-19 was independent of administration of a COVID-19 vaccine post-infection. Furthermore, we identified a subgroup of patients with severe COVID-19 that presented with persistently low CD8+ T-cell counts at follow-up and exhibited a distinct phenotype during acute infection consisting of a dysfunctional T-cell response and signs of excessive pro-inflammatory cytokine production. CONCLUSION: Our study suggests that T-cell numbers and function recover in most patients after COVID-19. However, we find evidence of persistent T-cell activation up to 12 months after infection and describe a subgroup of severe COVID-19 patients with persistently low CD8+ T-cell counts exhibiting a dysregulated immune response during acute infection.

Autoantibodies in COVID-19 correlate with antiviral humoral responses and distinct immune signatures.

BACKGROUND: Several autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. In this study, we longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID-19. METHODS: We performed highly sensitive indirect immunofluorescence assays to detect antinuclear antibodies (ANA) and antineutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome-wide serological profiling in a multicentric cohort of 175 COVID-19 patients followed up to 1 year after infection, eleven vaccinated individuals, and 41 unexposed controls. RESULTS: Compared with healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID-19 and recovery. However, the paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID-19. Furthermore, patients with severe COVID-19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS-CoV-2-specific antibody titers in COVID-19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen-specific humoral responses. Notably, the qualitative breadth of antibodies cross-reactive with other coronaviruses was comparable in ANA-positive and ANA-negative individuals during acute COVID-19. In autoantibody-positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID-19 and alterations of the B-cell compartment after recovery. CONCLUSION: Highly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS-CoV-2 infection, while the presence of autoantibodies in COVID-19 patients correlated with increased antiviral humoral immune responses and inflammatory immune signatures.

Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19.

BACKGROUND: Whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody tests are increasingly being used to estimate the prevalence of SARS-CoV-2 infection, the determinants of these antibody responses remain unclear. OBJECTIVES: Our aim was to evaluate systemic and mucosal antibody responses toward SARS-CoV-2 in mild versus severe coronavirus disease 2019 (COVID-19) cases. METHODS: Using immunoassays specific for SARS-CoV-2 spike proteins, we determined SARS-CoV-2-specific IgA and IgG in sera and mucosal fluids of 2 cohorts, including SARS-CoV-2 PCR-positive patients (n = 64) and PCR-positive and PCR-negtive health care workers (n = 109). RESULTS: SARS-CoV-2-specific serum IgA titers in patients with mild COVID-19 were often transiently positive, whereas serum IgG titers remained negative or became positive 12 to 14 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers after symptom onset. Very high titers of SARS-CoV-2-specific serum IgA were correlated with severe acute respiratory distress syndrome. Interestingly, some health care workers with negative SARS-CoV-2-specific serum antibody titers showed SARS-CoV-2-specific IgA in mucosal fluids with virus-neutralizing capacity in some cases. SARS-CoV-2-specific IgA titers in nasal fluids were inversely correlated with age. CONCLUSIONS: Systemic antibody production against SARS-CoV-2 develops mainly in patients with severe COVID-19, with very high IgA titers seen in patients with severe acute respiratory distress syndrome, whereas mild disease may be associated with transient production of SARS-CoV-2-specific antibodies but may stimulate mucosal SARS-CoV-2-specific IgA secretion.

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.

Profound dysregulation of T cell homeostasis and function in patients with severe COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and shows a broad clinical presentation ranging from asymptomatic infection to fatal disease. A very prominent feature associated with severe COVID-19 is T cell lymphopenia. However, homeostatic and functional properties of T cells are ill-defined in COVID-19. METHODS: We prospectively enrolled individuals with mild and severe COVID-19 into our multicenter cohort and performed a cross-sectional analysis of phenotypic and functional characteristics of T cells using 40-parameter mass cytometry, flow cytometry, targeted proteomics, and functional assays. RESULTS: Compared with mild disease, we observed strong perturbations of peripheral T cell homeostasis and function in severe COVID-19. Individuals with severe COVID-19 showed T cell lymphopenia and redistribution of T cell populations, including loss of naïve T cells, skewing toward CD4+ T follicular helper cells and cytotoxic CD4+ T cells, and expansion of activated and exhausted T cells. Extensive T cell apoptosis was particularly evident with severe disease and T cell lymphopenia, which in turn was accompanied by impaired T cell responses to several common viral antigens. Patients with severe disease showed elevated interleukin-7 and increased T cell proliferation. Furthermore, patients sampled at late time points after symptom onset had higher T cell counts and improved antiviral T cell responses. CONCLUSION: Our study suggests that severe COVID-19 is characterized by extensive T cell dysfunction and T cell apoptosis, which is associated with signs of homeostatic T cell proliferation and T cell recovery.

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.

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

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

Hemodynamic response of restoring sinus rhythm in critically ill patients with atrial fibrillation.

BACKGROUND: Electrical cardioversion (ECV) is the recommended treatment for atrial fibrillation (AFib) in critically ill patients, despite lacking data showing hemodynamic benefits of restoring sinus rhythm in this setting. The aim of this study was to assess the hemodynamic effect of successful ECV in a cohort of hemodynamically unstable critically ill patients. METHODS AND RESULTS: This study included 66 successful ECV performed in hemodynamically unstable critically ill patients with new-onset AFib. The primary outcome was the requirement of norepinephrine and inotropes 6 h after successful ECV in relation to baseline. Baseline norepinephrine dose was 0.19 ± 0.02 µg/kg/min, and 67% of patients were treated with positive inotropic drugs. Six hours after ECV, 33 patients (50%) were considered hemodynamic non-responders. Overall, the mean norepinephrine dose at 6 h was 0.17 ± 0.02 µg/kg/min (P = 0.051 compared to baseline) and 61% of patients were on inotropes (P = 0.13 compared to baseline). During the 6-hour period after ECV the mean norepinephrine dose temporary increased to 0.20 ± 0.02 µg/kg/min (P = 0.033 compared to baseline). CONCLUSIONS: ECV is associated with a large proportion of hemodynamic non-responders and a numerically modest, non-significant hemodynamic improvement in critically ill patients with new-onset AFib.

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.

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.

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.

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.

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.

Dexmedetomidine-Associated Hyperthermia: A Series of 9 Cases and a Review of the Literature.

Dexmedetomidine, an α2-adrenergic agonist, can be used to perform mild to moderate sedation in critically ill patients. In this case series, 9 cardiovascular intensive care unit patients with hyperthermia during dexmedetomidine administration, suggestive of drug fever, are presented. Hyperthermia (>38.5°C) occurred 6 (4-10) hours (median [interquartile range]) after dexmedetomidine initiation at a dose of 1.0 (0.8-1.3) µg/kg/h and was resolved 3 (1-8) hours after discontinuation of dexmedetomidine. All patients were screened for infectious and noninfectious causes of hyperthermia, and the findings were analyzed by 2 adverse drug reaction (ADR) assessment methods-the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) Causality Assessment and the Naranjo ADR scale. This resulted in a "probable" ADR in all 9 patients (WHO) and a "probable" and "possible" ADR in 1 and 8 patients (Naranjo), respectively. This case series supports published case reports, suggesting that dexmedetomidine administration may be associated with the occurrence of clinically relevant hyperthermia. The underlying mechanisms and risk factors are uncertain and require further research.

Delirium in the intensive care setting: A reevaluation of the validity of the CAM-ICU and ICDSC versus the DSM-IV-TR in determining a diagnosis of delirium as part of the daily clinical routine.

BACKGROUND: In the intensive care setting, delirium is a common occurrence that comes with subsequent adversities. Therefore, several instruments have been developed to screen for and detect delirium. Their validity and psychometric properties, however, remain controversial. METHOD: In this prospective cohort study, the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) were evaluated versus the DSM-IV-TR in the diagnosis of delirium with respect to their validity and psychometric properties. RESULTS: Out of some 289 patients, 210 with matching CAM-ICU, ICDSC, and DSM-IV-TR diagnoses were included. Between the scales, the prevalence of delirium ranged from 23.3% with the CAM-ICU, to 30.5% with the ICDSC, to 43.8% with the DSM-IV-TR criteria. The CAM-ICU showed only moderate concurrent validity (Cohen's κ = 0.44) and sensitivity (50%), but high specificity (95%). The ICDSC also reached moderate agreement (Cohen's κ = 0.60) and sensitivity (63%) while being very specific (95%). Between the CAM-ICU and the ICDSC, the concurrent validity was again only moderate (Cohen's κ = 0.56); however, the ICDSC yielded higher sensitivity and specificity (78 and 83%, respectively). SIGNIFICANCE OF RESULTS: In the daily clinical routine, neither the CAM-ICU nor the ICDSC, common tools used in screening and detecting delirium in the intensive care setting, reached sufficient concurrent validity; nor did they outperform the DSM-IV-TR diagnostic criteria with respect to sensitivity or positive prediction, but they were very specific. Thus, the non-prediction by the CAM-ICU or ICDSC did not refute the presence of delirium. Between the CAM-ICU and ICDSC, the ICDSC proved to be the more accurate instrument.

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.

Disappointing Success of Electrical Cardioversion for New-Onset Atrial Fibrillation in Cardiosurgical ICU Patients.

OBJECTIVES: To assess the success of electrical cardioversion for the treatment of new-onset atrial fibrillation in critically ill patients and to evaluate the stability of sinus rhythm in responders during the subsequent 24 hours. DESIGN: Retrospective study. SETTING: Twelve-bed cardiosurgical ICU at a university hospital. PATIENTS: Seventy-two consecutive patients with postoperative new-onset atrial fibrillation (<7 d of duration) treated by electrical cardioversion. INTERVENTIONS: Electrical cardioversion using synchronized biphasic shocks. MEASUREMENTS AND MAIN RESULTS: During 144 electrical cardioversions, 209 shocks were delivered to 72 patients. Maximal energy (200 J) was used in 85% of shocks. Electrical cardioversion immediately restored sinus rhythm in 102 sessions (71%). Pretreatment with amiodarone did not increase the success rates. During the follow-up, the percentages of sinus rhythm decreased from 43% after 1 hour to 23% after 24 hours. However, at ICU discharge, 54 patients (75%) were in sinus rhythm. Of the 54 patients in sinus rhythm, only 18 (33%) converted to sinus rhythm after repeated cardioversions, whereas the remaining 36 (66%) did so spontaneously or with amiodarone. CONCLUSIONS: Biphasic electrical cardioversion in cardiosurgical ICU patients was immediately successful in restoring sinus rhythm in 71% of sessions. However, early relapse of atrial fibrillation was common in the 24-hour follow-up. At ICU discharge, the majority of patients were in sinus rhythm, but the efficacy of repetitive electrical cardioversion in restoring sinus rhythm was disappointing.