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ABSTRACTObjectivesIntensive care unit (ICU) survivors are often left with impairments in physical, mental and cognitive functioning (Post-Intensive Care Syndrome (PICS)). We evaluated the organization, the feasibility for caregivers and patients and the patients’ appreciation of a post-ICU consultation aiming to detect these PICS-symptoms.MethodsA single-center prospective observational pilot study was conducted during an 18 month-period in the surgical ICU of a tertiary care hospital. Consecutive adult patients with an ICU-stay of ≥8 days and a favorable baseline quality of life (utility index ≥0.6 on EQ-5D-3 L) were eligible for inclusion. A post-ICU follow-up consultation consisting of a structured interview was scheduled 3 months after hospital discharge. Characteristics of the consultation (CG) and no consultation group (NCG) were compared. P-values <0.05 were considered significant.ResultsOf 133 eligible patients, 85 (64%) consented for the study and 42 (49%) attended the consultation. A total of 148 phone calls were made to schedule the consultations. Consultations took a median of 68 (61–74) minutes. Compared to CG-patients, NCG-patients were more often discharged to a care facility (P = 0.003) and had more problems with mobility (P = 0.014), self-care (P < 0.001) and usual activities (P = 0.005) after 3 months. At least one PICS-related problem was documented in all patients in the CG and NCG. Thirty-four CG-patients (81%) appreciated the initiative.ConclusionOrganizing an ICU-follow-up consultation was difficult and feasibility was low, but most attending patients appreciated the initiative. Better developed structures for ICU-follow-up are needed in view of the high number of PICS-related problems documented.

Critical COVID-19 patients admitted to the intensive care unit (ICU) frequently suffer from severe multiple organ dysfunction with underlying widespread cell death. Ferroptosis and pyroptosis are two detrimental forms of regulated cell death that could constitute new therapeutic targets. We enrolled 120 critical COVID-19 patients in a two-center prospective cohort study to monitor systemic markers of ferroptosis, iron dyshomeostasis, pyroptosis, pneumocyte cell death and cell damage on the first three consecutive days after ICU admission. Plasma of 20 post-operative ICU patients (PO) and 39 healthy controls (HC) without organ failure served as controls. Subsets of COVID-19 patients displayed increases in individual biomarkers compared to controls. Unsupervised clustering was used to discern latent clusters of COVID-19 patients based on biomarker profiles. Pyroptosis-related interleukin-18 accompanied by high pneumocyte cell death was independently associated with higher odds at mechanical ventilation, while the subgroup with high interleuking-1 beta (but limited pneumocyte cell death) displayed reduced odds at mechanical ventilation and lower mortality hazard. Meanwhile, iron dyshomeostasis with a tendency towards higher ferroptosis marker malondialdehyde had no association with outcome, except for the small subset of patients with very high catalytic iron independently associated with reduced survival. Forty percent of patients did not have a clear signature of the cell death mechanisms studied in this cohort. Moreover, repeated moderate levels of soluble receptor of advanced glycation end products and growth differentiation factor 15 during the first three days after ICU admission are independently associated with adverse clinical outcome compared to sustained lower levels. Altogether, the data point towards distinct subgroups in this cohort of critical COVID-19 patients with different systemic signatures of pyroptosis, iron dyshomeostasis, ferroptosis or pneumocyte cell death markers that have different outcomes in ICU. The distinct groups may allow ‘personalized’ treatment allocation in critical COVID-19 based on systemic biomarker profiles.

Study objectives: The survival rate of patients with a hematologic malignancy requiring mechanical ventilation (MV) in the ICU has improved over the last few decades. The objective of this study [...]

AbstractIntroductionThe incidence of adverse events in day surgery is an important quality indicator. This retrospective study investigated factors independently associated with unanticipated admission of pediatric patients after ambulatory surgery.Patients and methodsAmbulatory pediatric patients requiring unanticipated admission between January 2016 and December 2018 were compared to ambulatory pediatric patients who were discharged home after a planned surgery. Demographic data, organizational data, American Society of Anesthesiologists (ASA) classification, type of surgery, type of anesthesia, length of surgery, time of completion of the surgery, campus site, and season were collected in both groups. The reason for unexpected admission was classified according to four subtypes: anesthetic, medical, social/organizational and surgical reason, respectively. Multivariate logistic regression was used to identify independent factors associated with unanticipated admission.ResultsFrom a total of 4235 pediatric patients, 78 children (1.9%) required unanticipated admission. The reasons for admission were anesthetic n = 29 (37.3%), surgical n = 20 (25.6%), medical n = 16 (20.5%) and social/organizational n = 13 (16.6%). Age <2 years (odds ratio [OR] 3.005, 95% confidence interval (CI) 1.500–6.018; ASA class 2 (OR 2.144; 95% CI 1.193–3.852); ASA class 3 (OR 11.617; CI 5.698–23.685); length of surgery >2 h (OR 3.056; CI 1.829–5.107); completion of surgery > 2:30 PM (OR 3.507; CI 1.854–6.633) and campus site (OR 3.628; CI 1.991–6.610) were factors significantly associated with unanticipated admission.ConclusionChildren are less likely to be admitted after ambulatory surgery when preoperatively carefully selected and when prioritized considering age, general health condition and invasiveness of the surgery.

Hyperbilirubinemia is frequent in patients with hematological malignancies admitted to the intensive care unit (ICU). Literature about hepatic dysfunction (HD) in this context is scarce.

Early intensive care unit (ICU) admission, in Critically Ill Cancer Patients (CICP), is believed to have contributed to the prognostic improvement of critically ill cancer patients. The primary objective of this study was to assess the association between early ICU admission and hospital mortality in CICP.

High incidence of thrombosis in COVID‐19 patients indicates a hypercoagulable state. Hence, exploring the involvement of antiphospholipid antibodies (aPL) in these patients is of interest.

ICU patients/surrogates may experience adverse outcomes related to perceived inappropriate treatment. The objective was to determine the prevalence of patient/surrogate-reported perceived inappropriate treatment, its impact on adverse outcomes, and discordance with clinicians.

Most health care organizations' efforts to reduce harm focus on physical harm, but other forms of harm are both prevalent and important. These “nonphysical” harms can be framed using the concepts of respect and dignity: Disrespect is an affront to dignity and can cause harm. Organizations should strive to eliminate disrespect to patients, to families, and among health care professionals.

We developed a prediction model for quality of life (QOL) 1 year after intensive care unit (ICU) discharge based upon data available at the first ICU day to improve decision-making.

A typical hemolytic uremic syndrome (aHUS) presents similarly to thrombotic thrombocytopenic purpura (TTP) and other causes or conditions with thrombotic microangiopathy (TMA), such as disseminated intravascular coagulation or sepsis. Similarity in clinical presentation may hinder diagnosis and optimal treatment selection in the urgent setting in the ICU. However, there is currently no consensus on the diagnosis or treatment of aHUS for ICU specialists. This review aims to summarize available data on the diagnosis and treatment strategies of aHUS in the ICU to enhance the understanding of aHUS diagnosis and outcomes in patients managed in the ICU. To this end, a review of the recent literature (January 2009-March 2016) was performed to select the most relevant articles for ICU physicians. Based on the paucity of adult aHUS cases overall and within the ICU, no specific recommendations could be formally graded for the critical care setting. However, we recognize a core set of skills required by intensivists for diagnosing and managing patients with aHUS: recognizing thrombotic microangiopathies, differentiating aHUS from related conditions, recognizing involvement of other organ systems, understanding the pathophysiology of aHUS, knowing the diagnostic workup and relevant outcomes in critically ill patients with aHUS, and knowing the standard of care for patients with aHUS based on available data and guidelines. In conclusion, managing critically ill patients with aHUS requires basic skills that, in the absence of sufficient data from patients treated within the ICU, can be gleaned from an increasingly relevant literature outside the ICU. More data on critically ill patients with aHUS are needed to validate these conclusions within the ICU setting.

The benefit of the ICU for older patients is often debated. There is little knowledge on subjective impressions of excessive care in ICU nurses and physicians combined with objective patient data in real-life cases.

ICU care providers often feel that the care given to a patient may be inconsistent with their professional knowledge or beliefs. This study aimed to assess differences in, and reasons for, perceived inappropriate care (PIC) across ICU care providers with varying levels of decision-making power.

Increased use of advanced life-sustaining measures in patients with poor long-term expectations secondary to more chronic organ dysfunctions, comorbidities andor a poor quality of life has become a worrying trend over the last decade. This can lead to futile, disproportionate or inappropriate care in the ICU. This review summarizes the causes and consequences of disproportionate care in the ICU.

AbstractObjective:To evaluate the influence of matching on exposure time on estimates of attributable mortality of nosocomial bacteremia as assessed by matched cohort studies.Design:Two retrospective, pairwise-matched (1:2) cohort studies.Setting:A 54-bed intensive care unit (ICU) in a university hospital.Patients:Patients with nosocomial Escherichia colibacteremia (n = 68) and control-patients without nosocomial bacteremia (n = 136 for each matched cohort study).Intervention:In both matched cohort studies, the same set of bacteremic patients was matched with control-patients using the APACHE II system. In the first study, control-patients were required to have an ICU stay at least as long as the respective bacteremic patient prior to onset of bacteremia (matching on exposure time). In the second study, control-patients were required to have an ICU stay shorter than the stay prior to the development of bacteremia in the respective bacteremic patient (no matching on exposure time).Results:For bacteremic patients, the mean ICU stay before onset of the bacteremia was 9 days (median, 6 days). In the first matched cohort study, hospital mortality was not different between bacteremic patients and control-patients (44.1% vs 43.4%; P= .999). In the second study, mortality of bacteremic patients and control-patients was also not different (44.1% vs 47.8%; P= .657). Mortality rates between control groups were not different (43.4% vs 47.8%; P= .543).Conclusion:Matching or not matching on exposure time did not alter the estimate of attributable mortality for ICU patients with E. colibacteremia.

Starting renal replacement therapy (RRT) for acute renal failure in critically ill patients with haematological malignancies is controversial because of the poor outcome and high costs. The aim of this study was to compare the outcome between critically ill medical patients with and without haematological malignancies who received RRT for acute renal failure.

Background:Acute renal failure (ARF) in patients with sepsis provokes high mortality and financial cost. In this prospective study, we collected characteristics of patients in the intensive care unit (ICU) who developed sepsis/systemic inflammatory response syndrome (SIRS) to analyze differences between those who subsequently did or did not develop ARF. Methods:All patients admitted to the ICU of the University Hospital Gent, Belgium, between January 1, 2001, and December 31, 2001, who developed sepsis/SIRS were included if they had a serum creatinine level less than 2 mg/dL (<177 μmol/L). Results:Of 2,442 patients admitted to the ICU, 257 patients developed sepsis/SIRS. Of those, 29 patients (11%) developed ARF. In a univariate analysis, age, central venous pressure (CVP), and serum creatinine and blood urea nitrogen levels were greater (P= 0.003, P= 0.006, P< 0.001, and P< 0.001, respectively), whereas mean arterial and diastolic blood pressures, 24-hour urinary output, arterial pH, bicarbonate level, thrombocyte count, albumin level, and prothrombin time were lower (P= 0.05, P= 0.004, P= 0.005, P= 0.03, P= 0.009, P= 0.037, P= 0.05, and P= 0.006, respectively) in the ARF group. Prevalence of diabetes, sex, and need for ventilation were not different between the ARF and no-ARF groups, but in the ARF group, diuretic use, vasopressor use, and presence of primary hepatic failure were more prevalent (P= 0.001 for each). In a multivariate analysis, age, serum creatinine level, CVP, and presence of liver failure significantly contributed to a logistic regression model for ARF. Conclusion:Several parameters already were disturbed at the first day of SIRS/sepsis in patients who later developed ARF. Older age, elevated serum creatinine level despite elevated CVP, and presence of hepatic failure are predictive for ARF in septic patients.

Rheumatoid arthritis is an autoimmune disease which is characterized by chronic polyarthritis and joint destruction as well as by extra-articular manifestations, typically including the appearance of rheumatoid nodules. Although the pathogenesis of the disease is unknown, substantial evidence suggests that it is T cell-mediated. In contrast to experimental models, the disease-mediating T cells in the human situation have never been isolated or identified. We expanded T lymphocytes from human rheumatoid nodules by IL-2 stimulation and observed a marked oligoclonality among these expanded lymphocytes. This tendency towards oligoclonality was not seen in IL-2-expanded lymphocytes from peripheral blood. We hypothesize that this oligoclonal expansion reflects a clonally restricted in situ preactivation of lymphocytes and that precisely these preactivated cells are involved in the pathogenesis of the rheumatic process. Copyright 1993, 1999 Academic Press

The characteristics and impact of bacteremia have not been widely investigated in immunocompromised patients with acute respiratory failure (ARF).

Objective: To report a case of fatal alveolar hemorrhage associated with the use of everolimus in a patient who underwent a solid organ transplant.Case Summary: In a 71-year-old cardiac transplant patient, ciclosporine was replaced with everolimus because of worsening renal function. Over the following weeks, the patient developed nonproductive cough and increasing dyspnea. His condition deteriorated to acute respiratory failure with hemoptysis, requiring hospital admission. Bilateral patchy alveolar infiltrates were apparent on chest X-ray and computed tomography. Cardiac failure was ruled out and empiric antimicrobial therapy was initiated. Additional extensive workup could not document opportunistic infection. Everolimus was discontinued and high-dose corticosteroid therapy was initiated. Despite this, the patient required invasive mechanical ventilation and died because of refractory massive hemoptysis. Autopsy revealed diffuse alveolar hemorrhage.Discussion: Everolimus is a mammalian target of rapamycin inhibitor approved for use as an immunosuppressant and antineoplastic agent. Its main advantage over calcineurin inhibitors (tacrolimus and cyclosporine) is a distinct safety profile. Although it has become clear that everolimus induces pulmonary toxicity more frequently than initially thought, most published cases thus far represented mild and reversible disease, and none was fatal. Here, we report a case of pulmonary toxicity developing over weeks following the introduction of everolimus, in which a fatal outcome could not be prevented by drug withdrawal and corticosteroid treatment. The association of everolimus and this syndrome was probable according to the Naranjo probability scale.Conclusions: This case indicates that with the increasing use of everolimus, clinicians should be aware of the rare, but life-threatening manifestation of pulmonary toxicity.

The idea that multidrug resistance (MDR) to antibiotics in pathogens causing ventilator-associated pneumonia (VAP) is an independent risk factor for adverse outcome is still debated. We aimed to identify the determinants of MDR versus non-MDR microbial aetiology in VAP and assessed whether MDR versus non-MDR VAP was independently associated with increased 30-day mortality.

Introduction Tacrolimus is an important immunosuppressive drug for organ transplantation patients. It has a narrow therapeutic range, toxic side effects, and a blood concentration with wide intra- and interindividual variability. Hence, it is of the utmost importance to monitor tacrolimus blood concentration, thereby ensuring clinical effect and avoiding toxic side effects. Prediction models for tacrolimus blood concentration can improve clinical care by optimizing monitoring of these concentrations, especially in the initial phase after transplantation during intensive care unit (ICU) stay. This is the first study in the ICU in which support vector machines, as a new data modeling technique, are investigated and tested in their prediction capabilities of tacrolimus blood concentration. Linear support vector regression (SVR) and nonlinear radial basis function (RBF) SVR are compared with multiple linear regression (MLR).Methods Tacrolimus blood concentrations, together with 35 other relevant variables from 50 liver transplantation patients, were extracted from our ICU database. This resulted in a dataset of 457 blood samples, on average between 9 and 10 samples per patient, finally resulting in a database of more than 16,000 data values. Nonlinear RBF SVR, linear SVR, and MLR were performed after selection of clinically relevant input variables and model parameters. Differences between observed and predicted tacrolimus blood concentrations were calculated. Prediction accuracy of the three methods was compared after fivefold cross-validation (Friedman test and Wilcoxon signed rank analysis).Results Linear SVR and nonlinear RBF SVR had mean absolute differences between observed and predicted tacrolimus blood concentrations of 2.31 ng/ml (standard deviation [SD] 2.47) and 2.38 ng/ml (SD 2.49), respectively. MLR had a mean absolute difference of 2.73 ng/ml (SD 3.79). The difference between linear SVR and MLR was statistically significant (p < 0.001). RBF SVR had the advantage of requiring only 2 input variables to perform this prediction in comparison to 15 and 16 variables needed by linear SVR and MLR, respectively. This is an indication of the superior prediction capability of nonlinear SVR.Conclusion Prediction of tacrolimus blood concentration with linear and nonlinear SVR was excellent, and accuracy was superior in comparison with an MLR model.

Introduction The diagnosis of invasive pulmonary aspergillosis, according to the criteria as defined by the European Organisation for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG), is difficult to establish in critically ill patients. The aim of this study is to address the clinical significance of isolation of Aspergillus spp. from lower respiratory tract samples in critically ill patients on the basis of medical and radiological files using an adapted diagnostic algorithm to discriminate proven and probable invasive pulmonary aspergillosis from Aspergillus colonisation.Methods Using a historical cohort (January 1997 to December 2003), all critically ill patients with respiratory tract samples positive for Aspergillus were studied. In comparison to the EORTC/MSG criteria, a different appreciation was given to radiological features and microbiological data, including semiquantitative cultures and direct microscopic examination of broncho-alveolar lavage samples.Results Over a 7 year period, 172 patients were identified with a positive culture. Of these, 83 patients were classified as invasive aspergillosis. In 50 of these patients (60%), no high risk predisposing conditions (neutropenia, hematologic cancer and stem cell or bone marrow transplantation) were found. Typical radiological imaging (halo and air-crescent sign) occurred in only 5% of patients. In 26 patients, histological examination either by ante-mortem lung biopsy (n = 10) or necropsy (n = 16) was performed, allowing a rough estimation of the predictive value of the diagnostic algorithm. In all patients with histology, all cases of clinical probable pulmonary aspergillosis were confirmed (n = 17). Conversely, all cases classified as colonisation had negative histology (n = 9).Conclusion A respiratory tract sample positive for Aspergillus spp. in the critically ill should always prompt further diagnostic assessment, even in the absence of the typical hematological and immunological host risk factors. In a minority of patients, the value of the clinical diagnostic algorithm was confirmed by histological findings, supporting its predictive value. The proposed diagnostic algorithm needs prospective validation.

Candidemia and major organ candidiasis are problems that emerged in the past 2 decades and that are partially due to medical progress. Catheter-related thrombosis of the central veins is known to be a frequent but mostly subclinical complication of central venous lines. Although candidemia and catheter-related thrombosis are frequent, candida thrombophlebitis of the central veins is rarely reported. We recently successfully treated a 19-year-old polytrauma patient with candidal thrombophlebitis of the innominate vein. Despite catheter removal and therapy with amphotericin B, recurrent candidemia and signs of infection persisted, and a complete resection of the involved vein had to be performed. Only 16 well-documented cases of candidal thrombophlebitis of the central veins in adults have been reported over the past 20 years. An analysis of these 16 patients, together with our patient, is made in relation to risk factors, clinical features, diagnosis, therapy, and mortality.