Olanzapine postinjection delirium/sedation syndrome after long-acting olanzapine depot injection presenting to the emergency department: practical guidelines for diagnosis and management.

Olanzapine long-acting injection is a commonly used antipsychotic drug formulation in the treatment of schizophrenia. Postinjection delirium/sedation syndrome (PDSS) is a potential side effect of this intramuscular depot, for which patients are often presented at the ED. In this article, we give an overview of the current literature outlining the key aspects of managing this syndrome in a critical care setting, illustrated by a typical fictional clinical case. We discuss several useful and practical aspects of PDSS for emergency physicians and critical care physicians, including pharmacological background, common symptoms, diagnostic criteria and therapeutic options.

Age Moderates the Effect of Obesity on Mortality Risk in Critically Ill Patients With COVID-19: A Nationwide Observational Cohort Study.

OBJECTIVES: A high body mass index (BMI) is associated with an unfavorable disease course in COVID-19, but not among those who require admission to the ICU. This has not been examined across different age groups. We examined whether age modifies the association between BMI and mortality among critically ill COVID-19 patients. DESIGN: An observational cohort study. SETTING: A nationwide registry analysis of critically ill patients with COVID-19 registered in the National Intensive Care Evaluation registry. PATIENTS: We included 15,701 critically ill patients with COVID-19 (10,768 males [68.6%] with median [interquartile range] age 64 yr [55-71 yr]), of whom 1,402 (8.9%) patients were less than 45 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In the total sample and after adjustment for age, gender, Acute Physiology and Chronic Health Evaluation IV, mechanical ventilation, and use of vasoactive drugs, we found that a BMI greater than or equal to 30 kg/m 2 does not affect hospital mortality (adjusted odds ratio [OR adj ] = 0.98; 95% CI, 0.90-1.06; p = 0.62). For patients less than 45 years old, but not for those greater than or equal to 45 years old, a BMI greater than or equal to 30 kg/m 2 was associated with a lower hospital mortality (OR adj = 0.59; 95% CI, 0.36-0.96; p = 0.03). CONCLUSIONS: A higher BMI may be favorably associated with a lower mortality among those less than 45 years old. This is in line with the so-called "obesity paradox" that was established for other groups of critically ill patients in broad age ranges. Further research is needed to understand this favorable association in young critically ill patients with COVID-19.

Differential abundance of IgG antibodies against the spike protein of SARS-CoV-2 and seasonal coronaviruses in patients with fatal COVID-19.

Infection with the novel pandemic SARS-CoV-2 virus has been shown to elicit a cross-reactive immune response that could lead to a back-boost of memory recall to previously encountered seasonal (endemic) coronaviruses (eCoVs). Whether this response is associated with a fatal clinical outcome in patients with severe COVID-19 remains unclear. In a cohort of hospitalized patients, we have previously shown that heterologous immune responses to eCoVs can be detected in severe COVID-19. Here, we report that COVID-19 patients with fatal disease have decreased SARS-CoV-2 neutralizing antibody titers at hospital admission, which correlated with lower SARS-CoV-2 spike-specific IgG and was paralleled by a relative abundance of IgG against spike protein of eCoVs of the genus Betacoronavirus. Additional research is needed to assess if eCoV-specific back-boosted IgG is a bystander phenomenon in severe COVID-19, or a factor that influences the development of an efficient anti-viral immune response.

Frailty is associated with long-term outcome in patients with sepsis who are over 80 years old: results from an observational study in 241 European ICUs.

BACKGROUND: Sepsis is one of the most frequent reasons for acute intensive care unit (ICU) admission of very old patients and mortality rates are high. However, the impact of pre-existing physical and cognitive function on long-term outcome of ICU patients ≥ 80 years old (very old intensive care patients (VIPs)) with sepsis is unclear. OBJECTIVE: To investigate both the short- and long-term mortality of VIPs admitted with sepsis and assess the relation of mortality with pre-existing physical and cognitive function. DESIGN: Prospective cohort study. SETTING: 241 ICUs from 22 European countries in a six-month period between May 2018 and May 2019. SUBJECTS: Acutely admitted ICU patients aged ≥80 years with sequential organ failure assessment (SOFA) score ≥ 2. METHODS: Sepsis was defined according to the sepsis 3.0 criteria. Patients with sepsis as an admission diagnosis were compared with other acutely admitted patients. In addition to patients' characteristics, disease severity, information about comorbidity and polypharmacy and pre-existing physical and cognitive function were collected. RESULTS: Out of 3,596 acutely admitted VIPs with SOFA score ≥ 2, a group of 532 patients with sepsis were compared to other admissions. Predictors for 6-month mortality were age (per 5 years): Hazard ratio (HR, 1.16 (95% confidence interval (CI), 1.09-1.25, P < 0.0001), SOFA (per one-point): HR, 1.16 (95% CI, 1.14-1.17, P < 0.0001) and frailty (CFS > 4): HR, 1.34 (95% CI, 1.18-1.51, P < 0.0001). CONCLUSIONS: There is substantial long-term mortality in VIPs admitted with sepsis. Frailty, age and disease severity were identified as predictors of long-term mortality in VIPs admitted with sepsis.

Performance of the quick SOFA in very old ICU patients admitted with sepsis.

BACKGROUND: The number of very elderly ICU patients (abbreviated to VOPs; ≥80 years) with sepsis increases. Sepsis was redefined in 2016 (sepsis 3.0) using the quick SOFA (qSOFA) score. Since then, multiple studies have validated qSOFA for prognostication in different patient categories, but the prognostic value in VOPs with sepsis is still unknown. METHODS: Retrospective cohort study including patients admitted to Dutch ICUs with sepsis, in the period 2012 to 2016, evaluating the outcome and the performance of qSOFA, an extended qSOFA model, SOFA, SAPS II, and APACHE IV for hospital mortality. RESULTS: 5969 patients were included, of which 935 VOPs. Crude hospital mortality rates were 19%, 28%, and 39% for patients aged 18-65, 65-80, and ≥80 years respectively. Discriminative performance of qSOFA for in-hospital mortality in VOPs was poor (AUC 0.596) and lower than that of SOFA, APACHE IV, and SAPS II (0.704, 0.722, and 0.780 respectively). A qSOFA model extended with several other characteristics (AUC 0.643) was non-inferior to the full SOFA, but still inferior to APACHE IV and SAPS II, for all age groups. The Hosmer-Lemeshow goodness-of-fit test showed non-significant p-values for all models. Accuracy for both qSOFA and the extended qSOFA was lower compared to APACHE IV and SAPS II (Brier scores 0.227, 0.223, 0.184, and 0.183 respectively). CONCLUSION: The qSOFA showed worse discriminative performance to predict mortality than SOFA, APACHE IV, and SAPS II in both VOPs and younger patients admitted with sepsis.

Trends in hospital and intensive care admissions in the Netherlands attributable to the very elderly in an ageing population.

INTRODUCTION: The Dutch population is ageing and it is unknown how this is affecting trends in the percentage of hospital and intensive care unit (ICU) admissions attributable to patients aged 80 years or older, the very elderly. METHODS: We present data on the percentage of the very elderly in the general population and the percentage of hospital admissions attributable to the very elderly. We subsequently performed a longitudinal cross-sectional study on ICU admissions from hospitals participating in the National Intensive Care Evaluation registry for the period 2005 to 2014. We modeled the percentage of adult ICU admissions and treatment days attributable to the very elderly separately for ICU admissions following cardiac surgery and other reasons. RESULTS: The percentage of Dutch adults aged 80 years and older, increased from 4.5 % in 2005 to 5.4 % in 2014 (p-value < 0.0001) and with this ageing of the population, the percentage of hospital admissions attributable to very elderly increased from 9.0 % in 2005 to 10.6 % in 2014 (p-value < 0.0001). The percentage of ICU admissions following cardiac surgery attributable to the very elderly increased from 6.7 % in 2005 to 11.0 % in 2014 in nine hospitals (p-value < 0.0001), while the percentage of treatment days attributable to this group rose from 8.6 % in 2005 to 11.7 % in 2014 (p-value = 0.0157). In contrast, the percentage of very elderly patients admitted to the ICU for other reasons than following cardiac surgery remained stable at 13.8 % between 2005 and 2014 in 33 hospitals (p-value = 0.1315). The number of treatment days attributable to the very elderly rose from 11,810 in 2005 to 15,234 in 2014 (p-value = 0.0002), but the percentage of ICU treatment days attributable to this group remained stable at 12.0 % (p-value = 0.1429). CONCLUSIONS: As in many European countries the Dutch population is ageing and the percentage of hospital admissions attributable to the very elderly rose between 2005 and 2014. However, the percentage of ICU admissions and treatment days attributable to very elderly remained stable. The percentage of ICU admissions following cardiac surgery attributable to this group increased between 2005 and 2014.

The critically ill older patient with sepsis: a narrative review.

Sepsis is a significant public health concern, particularly affecting individuals above 70 years in developed countries. This is a crucial fact due to the increasing aging population, their heightened vulnerability to sepsis, and the associated high mortality rates. However, the morbidity and long-term outcomes are even more notable. While many patients respond well to timely and appropriate interventions, it is imperative to enhance efforts in identifying, documenting, preventing, and treating sepsis. Managing sepsis in older patients poses greater challenges and necessitates a comprehensive understanding of predisposing factors and a heightened suspicion for diagnosing infections and assessing the risk of sudden deterioration into sepsis. Despite age often being considered an independent risk factor for mortality and morbidity, recent research emphasizes the pivotal roles of frailty, disease severity, and comorbid conditions in influencing health outcomes. In addition, it is important to inquire about the patient's preferences and establish a personalized treatment plan that considers their potential for recovery with quality of life and functional outcomes. This review provides a summary of the most crucial aspects to consider when dealing with an old critically ill patient with sepsis.

[Which octogenarians benefit from the intensive care unit? A proposal for triage]. / Welke tachtigplussers profiteren van intensive care?

Intensive care unit (ICU) treatment can be associated with substantial suffering of patients, and those over eighty years old carry a much worse prognosis than younger ICU patients. Nevertheless, in the Netherlands we admit many people over the age of eighty to the ICU. Is this good practice? Whilst some elderly people may benefit, others don't. ICU treatment without mechanical ventilation is associated with less suffering, can still lead to a good outcome, and thus can often be justified in patients over eighty years. Full ICU treatment including prolonged mechanical ventilation, however, should only be used in selected cases.

The association of premorbid conditions with 6-month mortality in acutely admitted ICU patients over 80 years.

BACKGROUND: Premorbid conditions influence the outcome of acutely ill adult patients aged 80 years and over who are admitted to the ICU. The aim of this study was to determine the influence of such premorbid conditions on 6 month survival. METHODS: Prospective cohort study in 242 ICUs from 22 countries including patients 80 years or above, admitted over a 6 months period to an ICU between May 2018 and May 2019. Only emergency (acute) ICU admissions in adult patients ≥ 80 years of age were eligible. Patients who were admitted after planned/elective surgery were excluded. We measured the Clinical Frailty Scale (CFS), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), disability with the Katz activities of daily living (ADL) score, comorbidities and a Polypharmacy Score (CPS). RESULTS: Overall, the VIP2 study included 3920 patients. During ICU stay 1191 patients died (30.9%), and another 436 patients (11.1%) died after ICU discharge but within the first 30 days of admission, and an additional 895 patients died hereafter but within the first 6 months after admission (22.8%). The 6 months mortality was 64%. The median CFS was 4 (IQR 3-6). Frailty (CFS ≥ 5) was present in 26.6%. Cognitive decline (IQCODE above 3.5) was found in 30.2%. The median IQCODE was 3.19. A Katz ADL of 4 or less was present in 27.7%. Patients who surviving > 6 months were slightly younger (median age survivors 84 with IQR 81-86) than patients dying within the first 6 months (median age 84, IQR 82-87, p = 0.013), were less frequently frail (CFS > 5 in 19% versus 34%, p < 0.01) and were less dependent based on their Katz activities of daily living measurement (median Katz score 6, IQR 5-6 versus 6 points, IQR 3-6, p < 0.01). CONCLUSIONS: We found that Clinical Frailty Scale, age, and SOFA at admission were independent prognostic factors for 6 month mortality after ICU admission in patients age 80 and above. Adding other geriatric syndromes and scores did not improve the model. This information can be used in shared-decision making. CLINICALTRIALS: gov: NCT03370692.

Increased mortality in ICU patients ≥70 years old with COVID-19 compared to patients with other pneumonias.

BACKGROUND: Patients over 70 years old represent a substantial proportion of the COVID-19 ICU population and their mortality rates are high. The aim of this study is to describe the outcomes of patients ≥70 years old admitted to Dutch ICUs with COVID-19, compared to patients ≥70 years old admitted to the ICU for bacterial and other viral pneumonias, with adjustments for age, comorbidities, severity of illness, and ICU occupancy rate. METHODS: Retrospective cohort study including patients ≥70 years old admitted to Dutch ICUs, comparing patients admitted with COVID-19 from March 1st 2020 to January 1st 2022 with patients ≥70 years old admitted because of a bacterial and other viral pneumonia, both divided in a historical (i.e., January 1st 2017 to January 1st 2020) and current cohort (i.e., March 1st 2020 to January 1st 2022). Primary outcome is hospital mortality. RESULTS: 11,525 unique patients ≥70 years old admitted to Dutch ICUs were included; 5094 with COVID-19, 5334 with a bacterial pneumonia, and 1312 with another viral pneumonia. ICU-mortality and in-hospital mortality rates of the patients ≥70 years old admitted with COVID-19 were 39.7% and 47.6% respectively. ICU- and hospital mortality rates of the patients who were admitted in the same or in an historical time period with a bacterial pneumonia or other viral pneumonias were considerably lower (19.5% and 28.6% for patients with a bacterial pneumonia in the historical cohort and 19.1% and 28.8% in the same period, for the patients with other viral pneumonias 20.7% and 28.9%, and 22.7% and 31.8% respectively, all p < 0.001). Differences persisted after correction for several clinical characteristics and ICU occupancy rate. CONCLUSIONS: In ICU-patients ≥70 years old, COVID-19 is more severe compared to bacterial or viral pneumonia.

Impaired SARS-CoV-2 specific T-cell response in patients with severe COVID-19.

Cellular immune responses are of pivotal importance to understand SARS-CoV-2 pathogenicity. Using an enzyme-linked immunosorbent spot (ELISpot) interferon-γ release assay with wild-type spike, membrane and nucleocapsid peptide pools, we longitudinally characterized functional SARS-CoV-2 specific T-cell responses in a cohort of patients with mild, moderate and severe COVID-19. All patients were included before emergence of the Omicron (B.1.1.529) variant. Our most important finding was an impaired development of early IFN-γ-secreting virus-specific T-cells in severe patients compared to patients with moderate disease, indicating that absence of virus-specific cellular responses in the acute phase may act as a prognostic factor for severe disease. Remarkably, in addition to reactivity against the spike protein, a substantial proportion of the SARS-CoV-2 specific T-cell response was directed against the conserved membrane protein. This may be relevant for diagnostics and vaccine design, especially considering new variants with heavily mutated spike proteins. Our data further strengthen the hypothesis that dysregulated adaptive immunity plays a central role in COVID-19 immunopathogenesis.

Outcomes of Intensive Care Patients Older Than 90 Years: An 11-Year National Observational Study.

BACKGROUND/OBJECTIVES: Many intensive care unit (ICU) physicians are reluctant to admit patients aged 90 years and older, although evidence to support these decisions is scarce. Although the body of evidence on outcomes of patients aged 80 years and older is growing, it does not include patients aged 90 years and older. The aim of this study was to compare the short- and long-term mortality of ICU patients aged 90 years and older in the Netherlands with ICU patients aged 80 to 90 years, that is, octogenarians. DESIGN: Multicenter national cohort study over an 11-year period (2008-2018), using data of the National Intensive Care Evaluation (NICE) registry and the Dutch insurance claims registry. SETTING: All 82 ICUs in the Netherlands. PARTICIPANTS: All patients aged 80 years and older at the time of ICU admission. MEASUREMENTS: A total of 104,754 patients aged 80 years and older, of whom 9,495 (9%) were 90 years and older, were admitted to Dutch ICUs during the study period. RESULTS: ICU mortality of the patients aged 90 years and older was lower (13.8% vs 16.1%; P < .001) and hospital mortality was similar (26.1% vs 25.7%; P = .41) compared with octogenarians. After 3 months, mortality was higher for the patients aged 90 years and older (43.1% vs 33.7%; P < .001) and after 1-year mortality was 55.0% vs 42.7%; P < .001. CONCLUSION: In the Netherlands, mortality rates of patients aged 90 years and older admitted to the ICU are not as disappointing as often assumed. They have a lower ICU mortality and a similar hospital mortality compared with octogenarians. Nevertheless, their longer term mortality is higher compared with octogenarians. However, almost 3 of 4 patients leave the hospital alive, and almost half of the patients aged 90 years and older are still alive 1 year after their ICU admission. J Am Geriatr Soc 68:1842-1846, 2020.

Sepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study.

BACKGROUND: The number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival. RESULTS: This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81-86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs. 55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treatment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86-1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87-1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7-60.7) vs. 57.1% (95% CI 53.7-60.1), p = 0.85]. CONCLUSIONS: After adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival.

[Too old for the intensive care unit? Backgrounds and challenges]. / Te oud voor de Intensive Care? Achtergronden en uitdagingen.

More and more elderly patients are being admitted to the hospital. These elderly patients represent a significant proportion of intensive care unit (ICU) admissions. Older ICU patients have a high risk of death during their ICU admission and, if they do survive, a high risk of physical and cognitive decline. In addition, their remaining life expectancy is often limited. In short, elderly patients have less to gain from ICU treatment than young patients. It is therefore important to carefully consider the proportionality of ICU treatment. In this clinical lesson, we discuss aspects of the elderly ICU patient that should be taken into account when considering ICU treatment, in acute situations as well as in outpatient or GP settings.

Trends in short-term and 1-year mortality in very elderly intensive care patients in the Netherlands: a retrospective study from 2008 to 2014.

PURPOSE: To describe the trends in short-term and long-term mortality in very elderly intensive care unit (ICU) patients between 2008 and 2014. METHODS: A retrospective cohort study was conducted using data from the National Intensive Care Evaluation Foundation from 31 Dutch ICUs. Generalized linear mixed-effects models were used to determine the change in adjusted short-term mortality (ICU/hospital deaths) and long-term mortality (3, 6, and 12 months after ICU admission) over the period 2008-2014 in very elderly patients and in patients less than 80 years old admitted to the ICU. RESULTS: A total of 216,196 patients admitted to 31 ICUs in the period from 2008 to 2014 were included in the study, including 28,284 (13.1%) very elderly patients (80 years or older). Follow-up data for determination of 3-, 6-, and 12-month mortality were available for, respectively, 210,005 (97.1%), 202,551 (93.7%), and 176,847 (81.8%) ICU admissions. The crude ICU and in-hospital mortality decreased, respectively, from 17.6% to 13.0% and from 30.7% to 21.0%. The annual risk-adjusted ICU and in-hospital mortality of very elderly patients (adjusted for APACHE III score, comorbidities, and admission type) decreased significantly during the study period [adjusted odds ratio 0.97 (0.95-0.99) and 0.92 (0.91-0.93), respectively]. Additionally, the annual risk-adjusted 3-, 6-, and 12-month mortality decreased significantly from 2008 to 2014 [adjusted odds ratio 0.96 (0.95-0.97), 0.96 (0.94-0.97), and 0.97 (0.95-0.98), respectively]. A similar significant annual decrease in risk-adjusted short-term and long-term mortality was observed in patients aged less than 80 years. CONCLUSIONS: Both short-term and long-term risk-adjusted mortality decreased significantly during the study period in both very elderly ICU patients and patients aged less than 80 years in the Netherlands. This study clearly shows that in our setting very elderly patients benefit almost as much as their younger counterparts from improvement in quality of care over time.

Severe acute pancreatitis after EUS-FNA of a pancreatic cyst: a rare, but serious complication.

As a consequence of improved quality of abdominal imaging techniques in the last decades, discovery of pancreatic cystic lesions has become more common. The clinical significance of these lesions is often unclear and poses a diagnostic dilemma. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a subject of debate regarding its role in the diagnostic evaluation of pancreatic masses and cysts. Although risks associated with the procedure are low, consequences can be serious and even life-threatening. We report a case of a previously healthy 59-year-old woman who suffered severe acute pancreatitis after EUS-FNA of a pancreatic cyst, requiring admission to the intensive care unit (ICU). Development of infected pancreatic necrosis and, successively, bowel ischaemia, led to multiple organ failure. Despite maximal antibiotic and surgical treatment the patient succumbed to refractory septic shock. The fatal outcome of this case illustrates the importance of balanced decision-making in the diagnostic approach of pancreatic cystic lesions.

Dapsone hypersensitivity syndrome not related to G6PD deficiency.

Dapsone hypersensitivity syndrome (DHS) is a rare, but potentially life-threatening reaction to dapsone. We describe a 55-year-old Caucasian woman with normal glucose-6-phosphate dehydrogenase levels presenting with an extensive skin eruption, high-grade fever, pneumonitis and hepatitis, which occurred within 3 weeks after initiation of dapsone. In addition to supportive care, the patient was successfully treated with high-dose corticosteroids and antibiotics. The combination of high-grade fever, skin rash, lung and liver involvement made a dapsone hypersensitivity syndrome very likely.

Human metapneumovirus in adults.

Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination.