Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) is Highly Associated With Mortality and Persistent Organ Dysfunction in the Critically Ill: a Cohort Study

2020 ◽  
Author(s):  
Neha Alhad Sathe ◽  
Pavan K. Bhatraju ◽  
Carmen Mikacenic ◽  
Eric D. Morrell ◽  
W. Conrad Liles ◽  
...  

Abstract Background. The triggering receptor expressed on myeloid cells-1 (TREM-1) mediates fatal septic shock in murine models, but studies linking the soluble form of TREM-1 (sTREM-1) to mortality in clinical sepsis are inconclusive, and few have examined its relationship to organ dysfunction. We sought to identify associations between circulating sTREM-1 and both mortality and organ dysfunction among a broad cohort of critically ill medical, post-surgical and trauma patients. Methods. We enrolled a prospective cohort of patients who met two or more criteria for the systemic inflammatory response syndrome (SIRS) within 24 hours of intensive care unit (ICU) admission at a large academic medical center. sTREM-1 concentrations were measured at study enrollment. We used relative risk regression, adjusted for age, sex, and Charlson comorbidity index, to determine associations between sTREM-1 and the primary outcome of 28-day mortality. We also examined secondary outcomes of prevalent organ dysfunction on enrollment, and composites of persistent organ dysfunction or death at day 7. Results. Among 231 critically ill patients, non-survivors (n=19, 8%) had a higher proportion of pre-existing comorbidities, mechanical ventilation (79% vs. 44%) and shock (58% vs. 28%) compared to survivors. At study enrollment, increasing sTREM-1 was associated with a higher risk of severe acute kidney injury (AKI), shock, and acute hypoxemic respiratory failure requiring mechanical ventilation. sTREM-1 was higher among non-survivors than survivors (885 vs 336 pg/mL); each doubling of sTREM-1 concentration was associated with a 2.41-fold higher risk of 28-day mortality (95% CI 1.57, 3.72). Among 92 patients with shock on enrollment, doubling of sTREM-1 was associated with a 3.89-fold higher risk of persistent shock or death by day 7 (95% CI 1.85, 8.17). Higher sTREM-1 was also associated with a higher risk of both persistent AKI and persistent hypoxemic respiratory failure or death. Conclusions. Elevated plasma sTREM-1 is highly associated with 28-day mortality and organ dysfunction across a diverse critically ill population. These data support that early activation of the innate immune system plays a role in the development of organ dysfunction and death. Further studies should address whether modulation of the TREM-1 pathway might be beneficial in critically ill patients.

Thorax ◽  
2020 ◽  
Vol 75 (8) ◽  
pp. 623-631 ◽  
Author(s):  
Rohan Anand ◽  
Daniel F McAuley ◽  
Bronagh Blackwood ◽  
Chee Yap ◽  
Brenda ONeill ◽  
...  

PurposeAcute respiratory failure (ARF) is a common cause of admission to intensive care units (ICUs). Mucoactive agents are medications that promote mucus clearance and are frequently administered in patients with ARF, despite a lack of evidence to underpin clinical decision making. The aim of this systematic review was to determine if the use of mucoactive agents in patients with ARF improves clinical outcomes.MethodsWe searched electronic and grey literature (January 2020). Two reviewers independently screened, selected, extracted data and quality assessed studies. We included trials of adults receiving ventilatory support for ARF and involving at least one mucoactive agent compared with placebo or standard care. Outcomes included duration of mechanical ventilation. Meta-analysis was undertaken using random-effects modelling and certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation.ResultsThirteen randomised controlled trials were included (1712 patients), investigating four different mucoactive agents. Mucoactive agents showed no effect on duration of mechanical ventilation (seven trials, mean difference (MD) −1.34, 95% CI −2.97 to 0.29, I2=82%, very low certainty) or mortality, hospital stay and ventilator-free days. There was an effect on reducing ICU length of stay in the mucoactive agent groups (10 trials, MD −3.22, 95% CI −5.49 to −0.96, I2=89%, very low certainty).ConclusionOur findings do not support the use of mucoactive agents in critically ill patients with ARF. The existing evidence is of low quality. High-quality randomised controlled trials are needed to determine the role of specific mucoactive agents in critically ill patients with ARF.PROSPERO registration numberCRD42018095408.


Author(s):  
Aditi Balakrishna ◽  
Elisa C Walsh ◽  
Arzo Hamidi ◽  
Sheri Berg ◽  
Daniel Austin ◽  
...  

Abstract Purpose Preliminary reports suggest that critically ill patients with coronavirus disease 2019 (COVID-19) infection requiring mechanical ventilation may have markedly increased sedation needs compared with non–mechanically ventilated patients. We conducted a study to examine sedative use for this patient population within multiple intensive care units (ICUs) of a large academic medical center. Methods A retrospective, single-center cohort study of sedation practices for critically ill patients with COVID-19 during the first 10 days of mechanical ventilation was conducted in 8 ICUs at Massachusetts General Hospital, Boston, MA. The study population was a sequential cohort of 86 critically ill, mechanically ventilated patients with COVID-19. Data characterizing the sedative medications, doses, drug combinations, and duration of administration were collected daily and compared to published recommendations for sedation of critically ill patients without COVID-19. The associations between drug doses, number of drugs administered, baseline patient characteristics, and inflammatory markers were investigated. Results Among the study cohort, propofol and hydromorphone were the most common initial drug combination, with these medications being used on a given day in up to 100% and 88% of patients, respectively. The doses of sedative and analgesic infusions increased for patients over the first 10 days, reaching or exceeding the upper limits of published dosage guidelines for propofol (48% of patients), dexmedetomidine (29%), midazolam (7.7%), ketamine (32%), and hydromorphone (38%). The number of sedative and analgesic agents simultaneously administered increased over time for each patient, with more than 50% of patients requiring 3 or more agents by day 2. Compared with patients requiring 3 or fewer agents, as a group patients requiring more than 3 agents were of younger age, had an increased body mass index, increased serum ferritin and lactate dehydrogenase concentrations, had a lower PaO2:FIO2 (ratio of arterial partial pressure of oxygen to fraction of inspired oxygen), and were more likely to receive neuromuscular blockade. Conclusion Our study confirmed the clinical impression of elevated sedative use in critically ill, mechanically ventilated patients with COVID-19 relative to guideline-recommended sedation practices in other critically ill populations.


2020 ◽  
Vol 3 ◽  
Author(s):  
Jessica Hammes ◽  
Sikandar Khan ◽  
Heidi Lindroth ◽  
Babar Khan

Background:  COVID-19 is associated with severe respiratory failure and high mortality in critically ill patients.2,4,5 Neurologic manifestations of the disease, including delirium and coma, may also be associated with poor clinical outcomes. Delirium is associated with prolonged mechanical ventilation and mortality.3 this study sought to describe the rates, duration, and severity of delirium in patients admitted to the ICU with COVID-19.  Methods:  A retrospective, observational study was conducted from March 1stto April 27th, 2020, at Indiana University Health Methodist and Eskenazi Health Hospitals. The delirium measurements were extracted in the first 14 days of the ICU stay, using the Richmond Agitation and Sedation Scale (RASS) and the CAM-ICU and CAM-ICU7, for those with a positive COVID-19 diagnosis. The primary outcomes were delirium rates and duration; the secondary outcome was delirium severity. Descriptive statistics and median group comparisons were done using SAS v9.4.  Results:   Of 144 patients in the study, 73.6% experienced delirium and 76.4% experienced delirium or coma. The median delirium or coma duration was 7 days (IQR: 3-10), and the median delirium duration was 5 days (IQR: 2-7). The median CAM-ICU-7 score was 6 (IQR: 2-7) signifying severe delirium. Mechanical ventilation was associated increased risk of developing delirium (OR: 22.65, 95% CL: 5.24-97.82). Mortality was also more likely in patients experiencing delirium: 26.4% compared to 15.8% in patients without delirium.   Conclusion:   Of the 144 patients included, 73.6% experienced delirium lasting on average 5 days: the median delirium score being severe. Mechanical ventilation was also associated with greater odds of developing delirium. Because Covid-19 is associated with high rates of delirium, leading to increased rates of functionality disability, more resources and attention are needed to prevent and manage delirium in patients.1      References  Brummel NE, Jackson JC, Pandharipande PP, et al. Delirium in the ICU and subsequent long-term disability among survivors of mechanical ventilation. Critical Care Medicine. 2014;42(2):369-377.  Grasselli G, Pesenti A, Cecconi M. Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast During an Emergency Response. JAMA. 2020.   Hayhurst CJ, Pandharipande PP, Hughes CG. Intensive Care Unit Delirium: A Review of Diagnosis, Prevention, and Treatment. Anesthesiology. 2016;125(6):1229-1241.  Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020.  Wu Y, Xu X, Chen Z, et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain, behavior, and immunity. 2020:S0889-1591(0820)30357-30353. 


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 16001-16001
Author(s):  
M. Soares ◽  
M. Darmon ◽  
C. G. Ferreira ◽  
J. Salluh ◽  
S. De Miranda ◽  
...  

16001 Background: Recent advances in oncology and critical care have resulted in improved survival in critically ill cancer patients. An appraisal of the prognosis of critically ill patients with lung cancer is timely. Methods: The aim of this study was to evaluate the outcomes and prognostic factors of critically ill cancer patients with lung cancer. From 2000 to 2005, patients with either small-cell (SCLC) or non-small-cell lung cancer (NSCLC) admitted at two intensive care units (ICU) in Brazil and France were included. Patients with postoperative care, ICU stay <24 h and readmissions were excluded. Demographics, clinical, cancer related and outcome variables were collected. Hospital mortality was the outcome variable of interest. Variables selected in the univariate analysis (p < 0.25) and those considered clinically relevant were entered in a multivariable logistic regression analysis [results were expressed as odds-ratios (OR), 95% confidence interval (CI)]. Results: A total of 132 patients were studied (INCA = 87, St Louis Hospital = 45). Their mean age was 61 ± 10 years and 73% were males. Twenty-five (19%) had SCLC and 107 (81%), NSCLC. The SAPS II score was 48 ± 21 points. The main reasons for ICU admission were severe sepsis (45%) and acute respiratory failure (33%). During ICU stay, 96 (73%) patients received mechanical ventilation, 76 (58%) vasopressors and 11 (8%) dialysis; 15 (11%) patients were treated with chemotherapy and 6 (5%), radiation therapy. Thirty-eight (29%) patients had end-of-life decisions. ICU and hospital mortality were 43% and 60%, respectively. Multivariable analysis identified three independent determinants of hospital mortality: airway obstruction/infiltration by cancer [OR = 2.87 (1.34–8.13), p < 0.001], number of organ failures [OR = 1.91 (1.01–2.74), p = 0.047] and performance status 3–4 before admission [OR = 2.90 (0.94–8.95), p = 0.065]. Conclusions: Improved survival in overall ICU cancer patients extends to patients with lung cancer, including those needing mechanical ventilation. Interestingly, the characteristics of the cancer are not associated with the outcome and should not be the grounds for the ICU decision making. Mortality is increased with the number of organ dysfunctions, in particular when respiratory failure is due to cancer progression. No significant financial relationships to disclose.


2021 ◽  
Vol 30 (1) ◽  
pp. 77-79
Author(s):  
Peter A. Kahn ◽  
Malgorzata Cartiera ◽  
Walter Lindop ◽  
Robert L. Fogerty

Accurate height measurement is critical for accurate dosing of medications, mechanical ventilation, and nutritional calculations. Prior research has identified inaccuracies with self-reported height, and height is notably important to measure accurately in critically ill patients. In this study, conducted in a large tertiary academic medical center, medical records rarely indicated the method of height measurement, and there were statistically significant variations in measured height across admissions.


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