Insights from CTTACC: immune system reset by cellular therapies for chronic illness after trauma, infection, and burn.

BACKGROUND AIMS: In this paper, we present a review of several selected talks presented at the CTTACC conference (Cellular Therapies in Trauma and Critical Care) held in Scottsdale, AZ in May 2023. This conference review highlights the potential for cellular therapies to "reset" the dysregulated immune response and restore physiologic functions to normal. Improvements in medical care systems and technology have increasingly saved lives after major traumatic events. However, many of these patients have complicated post-traumatic sequelae, ranging from short-term multi-organ failure to chronic critical illness. METHODS/RESULTS: Patients with chronic critical illness have been found to have dysregulated immune responses. These abnormal and harmful immune responses persist for years after the initial insult and can potentially be mitigated by treatment with cellular therapies. CONCLUSIONS: The sessions emphasized the need for more research and clinical trials with cellular therapies for the treatment of a multitude of chronic illnesses: post-trauma, radiation injury, COVID-19, burns, traumatic brain injury (TBI) and other chronic infections.

Risk factors, biomarkers, and mechanisms for persistent inflammation, immunosuppression, and catabolism syndrome (PICS): a systematic review and meta-analysis.

INTRODUCTION: Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has been proposed as an endotype of chronic critical illness (CCI). The aim of this systematic review is to synthesise the available evidence of risk factors, biomarkers, and biological mechanisms underlying PICS. METHODS: MEDLINE, CENTRAL, and EMBASE were searched on June 2, 2023. Our population of interest was adult intensive care unit survivors. The exposure group was patients with PICS and the comparator group was patients with no PICS, CCI, or rapid recovery. Mean differences were pooled for each biomarker using a random effects DerSimonian-Laird method. Risk of bias assessment was done using the Newcastle-Ottawa Scale. RESULTS: Six papers were included. Five were single-centre retrospective cohort studies, and one was a prospective cohort study, with sample sizes ranging from 22 to 391 patients. Two studies showed an increased incidence of PICS with age, and two studies showed an association between PICS and Charlson Comorbidity Index scores. PICS was associated with requiring mechanical ventilation in four studies. Meta-analysis showed a 34.4 mg L-1 higher C-reactive protein (95% confidence interval [CI] 12.7-56.2 mg L-1; P<0.01), a 4.4 g L-1 lower albumin (95% CI 0.5-8.3 g L-1; P<0.01), and a 0.36×109 L-1 lower lymphocyte count (95% CI 0.25-0.47×109 L-1; P=0.01) in the PICS compared with the non-PICS group. There are a large variety of other potential biomarkers but limited validation studies. The overall quality of evidence is limited, and these results should be interpreted accordingly. CONCLUSIONS: While older patients and those with co-morbidities could be at greater risk for PICS, acquired risk factors, such as injury severity, are potentially more predictive of PICS than intrinsic patient characteristics. There are many potential biomarkers for PICS, but limited validation studies have been conducted. Persistent myeloid-derived suppressor cell expansion, the continual release of danger-associated molecular patterns and pathogen-associated molecular patterns propagating inflammation, and bioenergetic failure are all mechanisms underlying PICS that could offer potential for novel biomarkers and therapeutic interventions. CLINICAL TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO; CRD42023427749).

Persistent inflammation, immunosuppression, and catabolism syndrome (PICS): a review of definitions, potential therapies, and research priorities.

Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) is a clinical endotype of chronic critical illness. PICS consists of a self-perpetuating cycle of ongoing organ dysfunction, inflammation, and catabolism resulting in sarcopenia, immunosuppression leading to recurrent infections, metabolic derangements, and changes in bone marrow function. There is heterogeneity regarding the definition of PICS. Currently, there are no licensed treatments specifically for PICS. However, findings can be extrapolated from studies in other conditions with similar features to repurpose drugs, and in animal models. Drugs that can restore immune homeostasis by stimulating lymphocyte production could have potential efficacy. Another treatment could be modifying myeloid-derived suppressor cell (MDSC) activation after day 14 when they are immunosuppressive. Drugs such as interleukin (IL)-1 and IL-6 receptor antagonists might reduce persistent inflammation, although they need to be given at specific time points to avoid adverse effects. Antioxidants could treat the oxidative stress caused by mitochondrial dysfunction in PICS. Possible anti-catabolic agents include testosterone, oxandrolone, IGF-1 (insulin-like growth factor-1), bortezomib, and MURF1 (muscle RING-finger protein-1) inhibitors. Nutritional support strategies that could slow PICS progression include ketogenic feeding and probiotics. The field would benefit from a consensus definition of PICS using biologically based cut-off values. Future research should focus on expanding knowledge on underlying pathophysiological mechanisms of PICS to identify and validate other potential endotypes of chronic critical illness and subsequent treatable traits. There is unlikely to be a universal treatment for PICS, and a multimodal, timely, and personalised therapeutic strategy will be needed to improve outcomes for this growing cohort of patients.

Charting the course for improved outcomes in chronic critical illness: therapeutic strategies for persistent inflammation, immunosuppression, and catabolism syndrome (PICS).

Enhanced critical care delivery has led to improved survival rates in critically ill patients, yet sepsis remains a leading cause of multiorgan failure with variable recovery outcomes. Chronic critical illness, characterised by prolonged ICU stays and persistent end-organ dysfunction, presents a significant challenge in patient management, often requiring multifaceted interventions. Recent research, highlighted in a comprehensive review in the British Journal of Anaesthesia, focuses on addressing the pathophysiological drivers of chronic critical illness, such as persistent inflammation, immunosuppression, and catabolism, through targeted therapeutic strategies including immunomodulation, muscle wasting prevention, nutritional support, and microbiome modulation. Although promising avenues exist, challenges remain in patient heterogeneity, treatment timing, and the need for multimodal approaches.

Clinician-perceived barriers and facilitators for the provision of actionable processes of care important for persistent or chronic critical illness.

AIM: To explore clinician-perceived barriers to and facilitators for the provision of actionable processes of care important for patients with persistent or chronic critical illness. DESIGN: Qualitative descriptive interview study. METHODS: Secondary analysis of semi-structured telephone interviews (December 2018 - February 2019) with professionally diverse clinicians working with adults experiencing persistent or chronic critical illness in Canadian intensive care units. We used deductive content analysis informed by the Social-Ecological Model. RESULTS: We recruited 31 participants from intensive care units across nine Canadian provinces. Reported intrapersonal level barriers to the provision of actionable processes of care included lack of training, negative emotions and challenges prioritizing these patients. Facilitators included establishment of positive relations and trust with patients and family. Interpersonal barriers included communication difficulties, limited access to physicians and conflict. Facilitators included communication support, time spent with the patient/family and conflict management. Institutional barriers comprised inappropriate care processes, inadequate resources and disruptive environmental conditions. Facilitators were regular team rounds, appropriate staffing and employment of a primary care (nurse and/or physician) model. Community-level barriers included inappropriate care location and insufficient transition support. Facilitators were accessed to alternate care sites/teams and to formalized transition support. Public policy-level barriers included inadequacy of formal education programs for the care of these patients; knowledge implementation for patient management was identified as a facilitator. CONCLUSION: Our results highlighted multilevel barriers and facilitators to the delivery of actionable processes important for quality care for patient/family experiencing persistent or chronic critical illness. IMPACT: Using the Social-Ecological Model, the results of this study provide intra and interpersonal, institutional, community and policy-level barriers to address and facilitators to harness to improve the care of patients/family experiencing persistent or chronic critical illness. REPORTING METHOD: Consolidated criteria for reporting qualitative studies. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

A prolonged intensive care unit stay defines a worse long-term prognosis - Insights from the critically ill mortality by age (Cimba) study.

BACKGROUND: Patients with critical illness often survive the intensive care unit (ICU) at a cost of prolonged length of stay (LOS) and slow recovery. This chronic critically ill disease may lead to long-term poor outcomes, especially in older or frail patients. OBJECTIVES: The main goal of this study was to address the characteristics and outcomes of patients with prolonged ICU LOS. Mainly, short- and long-term admissions were compared to identify risk factors for persistent critical illness and to characterise the impact on ICU, hospital, and long-term mortality. METHODS: Subanalysis of a retrospective, multicentric, observational study addressing the 2-year outcome of patients admitted to Portuguese ICUs (the Cimba study). Patients were segregated according to an ICU LOS of ≥14 days. RESULTS: Data from 37 118 patients were analysed, featuring a median ICU LOS of 4 days (percentile: 25-75 2-9), and a mortality of 16.1% in the ICU, 24.0% in the hospital, and 38.7% after 2 years. A total of 5334 patients (14.4%) had an ICU LOS of ≥14 days (corresponding to 48.9% of all ICU patients/days). Patients with prolonged LOS were more often younger (52.8% vs 46.4%, were ≤65 years of age , p < 0.001), although more severe (Simplified Acute Physiology Score II: 49.1 ± 16.9 vs 41.8 ± 19.5, p < 0.001), and had higher ICU and hospital mortality (18.3% vs 15.7%, and 31.2 vs 22.8%, respectively). Prolonged ICU LOS was linked to an increased risk of dying during the 2-year follow-up (adjusted Cox proportional hazard: 1.65, p < 0.001). CONCLUSION: Prolonged LOS is associated with a long-term impact on patient prognosis. More careful planning of care should incorporate these data.

Consequences of a stay in the intensive care unit and outpatient follow-up care for chronic critically ill patients: A retrospective data analysis.

BACKGROUND: Patients with chronic critical illness (CCI) represent a particularly vulnerable patient population with significant quality-of-life consequences and a need for follow-up care. Existing research on their quality-of-life trajectory and outpatient follow-up care is limited. OBJECTIVES: The aim of this study was to (i) describe a quality improvement project focussing on patients with CCI in the Swiss setting; (ii) explain the consequences of an intensive care unit (ICU) stay for patients with CCI; and (iii) evaluate outpatient follow-up care for patients with CCI. METHODS: This retrospective descriptive mixed-methods longitudinal study used routine data from outpatient follow-up care between October 2018 and June 2022. The pre-ICU data were collected retrospectively for the week before ICU admission (baseline); prospectively at 3, 6, and 12 months after ICU discharge; and during an outpatient follow-up care at 6 months. Its main outcomes were health-related quality of life (HRQOL). Patients with CCI were defined as those having a ICU stay longer than 7 days. RESULTS: This study enrolled 227 patients with outpatient follow-up care, but only 77 were analysed at all four timepoints. Their EuroQol five-dimension five-level questionnaire-Visual Analogue Scale scores ranged from 0 to 100, with a median of 85 (interquartile range = 0-100) and a mean of 77.2 (standard deviation ± 23.52) before their ICU stay. Their scores had almost returned to the baseline 12 months after their ICU stay. While some reported existing restrictions in the individual HRQOL dimensions before their ICU stay, patients and their families appreciated the outpatient follow-up care including an ICU visit. CONCLUSION: Patients with CCI have different HRQOL trajectories over time. Patients with CCI can have a good HRQOL despite their impairments; however, the HRQOL trajectories of many patients remain unclear. The focus must be on identifying the illness trajectories and on measuring and maintaining their long-term HRQOL.

The effect of enteral nutrition nursing intervention on postoperative treatment of chronic critically ill patients: Health prevention data analysis.

The field of genomics has witnessed remarkable advancements, leading to the gradual clarification of the genetic mechanism underlying various cancers. As a result, there has been an increased emphasis on gene prevention and treatment. Against this backdrop, this paper aims to examine the impact of enteral nutrition nursing intervention on the postoperative treatment of patients with chronic critical illness, with a focus on health prevention. Based on an analysis of the clinical data of patients with chronic critical illness, the study found that enteral nutrition nursing intervention plays a crucial role in enhancing the nutritional status of patients, reducing the incidence of complications, shortening the length of hospital stay, and improving the effect of postoperative rehabilitation. The study's results provide valuable insights into the efficacy of enteral nutrition nursing intervention in the postoperative treatment of patients with chronic critical illness. By improving the nutritional status of patients, enteral nutrition nursing intervention can help reduce the risk of complications, shorten the length of hospital stay, and enhance the effectiveness of postoperative rehabilitation. These findings underscore the importance of adopting effective interventions such as enteral nutrition nursing to improve the therapeutic outcomes of chronic critical illness patients and achieve the goal of health prevention.

Vasopressin Response and Clinical Trajectory in Septic Shock Patients.

BACKGROUND: In septic shock, vasopressors aim to improve tissue perfusion and prevent persistent organ dysfunction, a characteristic of chronic critical illness (CCI). Adjunctive vasopressin is often used to decrease catecholamine dosage, but the association of vasopressin response with subsequent patient outcomes is unclear. We hypothesized vasopressin response is associated with favorable clinical trajectory. METHODS: We included patients with septic shock receiving vasopressin as a catecholamine adjunct in this retrospective cohort study. We defined vasopressin response as a lowering of the catecholamine dose required to maintain mean arterial pressure ≥65 mm Hg, 6 h after vasopressin initiation. Clinical trajectories were adjudicated as early death (ED; death before day 14), CCI (ICU stay ≥14 days with persistent organ dysfunction), or rapid recovery (RR; not meeting ED or CCI criteria). Trajectories were placed on an ordinal scale with ED the worst outcome, CCI next, and RR the best outcome. The association of vasopressin response with clinical trajectory was assessed with multivariable ordinal logistic regression. RESULTS: In total 938 patients were included; 426 (45.4%) were vasopressin responders. The most frequent trajectory was ED (49.8%), 29.7% developed CCI, and 20.5% had rapid recovery. In survivors to ICU day 14 (those without ED), 59.2% had CCI and 40.8% experienced RR. Compared with vasopressin non-responders, vasopressin responders less frequently experienced ED (42.5% vs. 55.9%) and more frequently experienced RR (24.6% vs. 17.0%; P < 0.01). After controlling for confounders, vasopressin response was independently associated with higher odds of developing a better clinical trajectory (OR 1.63; 95% CI 1.26-2.10). Medical patients most frequently developed ED and survivors more commonly developed CCI than RR; surgical patients developed the three trajectories with similar frequency (P < 0.01). CONCLUSIONS: Vasopressin responsive status was associated with improved clinical trajectory in septic shock patients. Early vasopressin response is a potential novel prognostic marker for short-term clinical trajectory.

Managing the Chronically Ventilated Critically Ill Population.

Advances in intensive care over the past few decades have significantly improved the chances of survival for patients with acute critical illness. However, this progress has also led to a growing population of patients who are dependent on intensive care therapies, including prolonged mechanical ventilation (PMV), after the initial acute period of critical illness. These patients are referred to as the "chronically critically ill" (CCI). CCI is a syndrome characterized by prolonged mechanical ventilation, myoneuropathies, neuroendocrine disorders, nutritional deficiencies, cognitive and psychiatric issues, and increased susceptibility to infections. It is associated with high morbidity and mortality as well as a significant increase in healthcare costs. In this article, we will review disease burden, outcomes, psychiatric effects, nutritional and ventilator weaning strategies as well as the role of palliative care for CCI with a specific focus on those requiring PMV.

High-flow via a tracheostomy tube and speaking valve during weaning from mechanical ventilation and tracheostomy.

BACKGROUND: Weaning from mechanical ventilation and tracheostomy after prolonged intensive care consume enormous resources with optimal management not currently well described. Restoration of respiratory flow via the upper airway is essential and early cuff-deflation using a one-way valve (OWV) is recommended. However, extended OWV use may cause dry airways and thickened secretions which challenge the weaning process. High-flow therapy via the tracheostomy tube (HFT-T) humidifies inspired air and may be connected via an in-line OWV (HFT-T-OWV) alleviating these problems. We aim to provide clinical and experimental data on the safety of HFT-T-OWV along with a practical guide to facilitate clinical use during weaning from mechanical ventilation and tracheostomy. METHODS: Data on adverse events of HFT-T-OWV were retrieved from a quality register for patients treated at an intensive care rehabilitation center between 2019 and 2022. Benchtop experiments were performed to measure maximum pressures and pressure support generated by HFT-T-OWV at 25-60 L/min flow using two different HFT-T adapters (interfaces). In simulated airway obstruction using a standard OWV (not in-line) maximum pressures were measured with oxygen delivered via the side port at 1-3 L/min. RESULTS: Of 128 tracheostomized patients who underwent weaning attempts, 124 were treated with HFT-T-OWV. The therapy was well tolerated, and no adverse events related to the practice were detected. The main reason for not using HFT-T-OWV was partial upper airway obstruction using a OWV. Benchtop experiments demonstrated HFT-T-OWV maximum pressures <4 cmH2 O and pressure support 0-0.6 cmH2 O. In contrast, 1-3 L/min supplemental oxygen via a standard OWV caused pressures between 84 and 148 cmH2 O during simulated airway obstruction. CONCLUSIONS: Current study clinical data and benchtop experiments indicate that HFT-T-OWV was well tolerated and appeared safe. Pressure support was low, but humidification may enable extended use of a OWV without dry airway mucosa and thickened secretions. Results suggest the treatment could offer advantages to standard OWV use, with or without supplementary oxygen, as well as to HFT-T without a OWV, for weaning from mechanical ventilation and tracheostomy. However, for definitive treatment recommendations, randomized clinical trials are needed.

Chronic critical illness after trauma injury: outcomes and experience in a trauma center.

OBJECTIVE: To determine the prevalence, risk factors and functional results of chronic critical illness (CCI) in polytrauma patients. DESIGN: Single-center observational retrospective study. SETTING: ICU at a tertiary hospital in Santander, Spain, between 2015 and 2019. PATIENTS: Adult trauma patients who survived beyond 48 h after injury. CCI was defined as the need for mechanical ventilation for at least 14 days or tracheostomy for difficult weaning. MEASUREMENTS AND MAIN RESULTS: About 62/575 developed CCI. These patients were characterized by higher ISS score [17 (SD 10) vs. 13.8 (SD 8.2); p < 0.001] and higher NISS (26 (SD 11) vs. 19.2 (SD 10.5); p = 0.001). CCI group had greater proportion of hospital-acquired infections (100% vs. 18.1%; p < 0.001), and acute kidney failure (33.9% vs. 22.8% p < 0.001). During the first 24 h of admission, CCI group required in a greater proportion surgical intervention (50% vs. 29%; p = 0.001), and blood products (31.3% vs. 20.5%; p < 0.047). Hospital ward stay was longer in CCI patients [9.5 days (IQR 5-16.9) vs. 43.9 (IQR 30.3-53) p < 0.001]. The CCI mortality was higher (19.5% vs. 8.1%; p = 0.004). Surgical intervention in the first 24 h (OR 2.5 95% CI 1.1-4.1), age (> 55 years) (OR 2.1 95%CI 1.1-4.2), ISS score (OR 1.1 95%CI 1.02-1.3), GCS score (OR 0.8 95%CI 0.4-23.2) and multiple organ failure (OR 9.5 95%CI 3.9-23.2) were predictors of CCI in the multivariate analysis. CONCLUSIONS: CCI after severe trauma appears in a considerable proportion of patients. Early identification and implementation of specific interventions could change the evolution of this process.

Comparing Long-Term Prognosis in Chronic Critically Ill Patients: A Case Series Study of Medical versus Surgical Sepsis.

Background and Objectives: Chronic critical illness (CCI) is a syndrome characterized by persistent organ dysfunction that requires critical care therapy for ≥14 days. Sepsis and respiratory failure constitute the two primary causes of CCI. A better understanding of this patient population and their clinical course may help to risk-stratify them early during hospitalization. Our objective was to identify whether the source of sepsis (medical versus surgical) affected clinical trajectory and prognosis in patients developing CCI. Materials and Methods: We describe a cohort of patients having acute respiratory failure and sepsis and requiring critical care therapy in the medical (MICU) or surgical (SICU) critical care units for ≥14 days. Given the relative infrequency of CCI, we use a case series design to examine mortality, functional status, and place of residence (home versus non-home) at one year following their index hospitalization. Results: In medical patients developing CCI (n = 31), the severity of initial organ dysfunction, by SOFA score, was significantly associated with the development of CCI (p = 0.002). Surgical patients with CCI (n = 7) experienced significantly more ventilator-free days within the first 30 days following sepsis onset (p = 0.004), as well as less organ dysfunction at day 14 post-sepsis (p < 0.0001). However, one-year mortality, one-year functional status, and residency at home were not statistically different between cohorts. Moreover, 57% of surgical patients and 26% of medical patients who developed CCI were living at home for one year following their index hospitalization (p = 0.11). Conclusions: While surgical patients who develop sepsis-related CCI experience more favorable 30-day outcomes as compared with medical patients, long-term outcomes do not differ significantly between groups. This suggests that reversing established organ dysfunction and functional disability, regardless of etiology, is more challenging compared to preventing these complications at an earlier stage.

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OBJECTIVES: To explore the etiology composition and outcomes of pediatric chronic critical illness (PCCI) in the pediatric intensive care unit (PICU). METHODS: The children who were hospitalized in the PICU of Dongguan Children's Hospital Affiliated to Guangdong Medical University and met the diagnostic criteria for PCCI from January 2017 to December 2022 were included in the study. The etiology of the children was classified based on their medical records and discharge diagnoses. Relevant clinical data during hospitalization were collected and analyzed. RESULTS: Among the 3 955 hospitalized children in the PICU from January 2017 to December 2022, 321 cases (8.12%) met the diagnostic criteria for PCCI. Among the 321 cases, the most common etiology was infection (71.3%, 229 cases), followed by unintentional injury (12.8%, 41 cases), postoperation (5.9%, 19 cases), tumors/immune system diseases (5.0%, 16 cases), and genetic and chromosomal diseases (5.0%, 16 cases). Among the 321 cases, 249 cases (77.6%) were discharged after improvement, 37 cases (11.5%) were discharged at the request of the family, and 35 cases (10.9%) died in the hospital. Among the deaths, infection accounted for 74% (26/35), unintentional injury accounted for 17% (6/35), tumors/immune system diseases accounted for 6% (2/35), and genetic and chromosomal diseases accounted for 3% (1/35). From 2017 to 2022, the proportion of PCCI in PICU diseases showed an increasing trend year by year (P<0.05). Among the 321 children with PCCI, there were 148 infants and young children (46.1%), 57 preschool children (17.8%), 54 school-aged children (16.8%), and 62 adolescents (19.3%), with the highest proportion in the infant and young children group (P<0.05). The in-hospital mortality rates of the four age groups were 14.9% (22/148), 8.8% (5/57), 5.6% (3/54), and 8.1% (5/62), respectively. The infant and young children group had the highest mortality rate, but there was no statistically significant difference among the four groups (P>0.05). CONCLUSIONS: The proportion of PCCI in PICU diseases is increasing, and the main causes are infection and unintentional injury. The most common cause of death in children with PCCI is infection. The PCCI patient population is mainly infants and young children, and the in-hospital mortality rate of infant and young children with PCCI is relatively high.

COVID-19 and Long-Term Outcomes: Lessons from Other Critical Care Illnesses and Potential Mechanisms.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that is currently causing a pandemic and has been termed coronavirus disease (COVID-19). The elderly or those with preexisting conditions like diabetes, hypertension, coronary heart disease, chronic obstructive pulmonary disease, cerebrovascular disease, or kidney dysfunction are more likely to develop severe cases when infected. Patients with COVID-19 admitted to the ICU have higher mortality than non-ICU patients. Critical illness has consistently posed a challenge not only in terms of mortality but also in regard to long-term outcomes of survivors. Patients who survive acute critical illness including, but not limited to, pulmonary and systemic insults associated with acute respiratory distress syndrome, pneumonia, systemic inflammation, and mechanical ventilation, will likely suffer from post-ICU syndrome, a phenomenon of cognitive, psychiatric, and/or physical disability after treatment in the ICU. Post-ICU morbidity and mortality continue to be a cause for concern when considering large-scale studies showing 12-month mortality risks of 11.8-21%. Previous studies have demonstrated that multiple mechanisms, including cytokine release, mitochondrial dysfunction, and even amyloids, may lead to end-organ dysfunction in patients. We hypothesize that COVID-19 infection will lead to post-ICU syndrome via potentially similar mechanisms as other chronic critical illnesses and cause long-term morbidity and mortality in patients. We consider a variety of mechanisms and questions that not only consider the short-term impact of the COVID-19 pandemic but its long-term effects that may not yet be imagined.

Detailed Characterization of Brain Dysfunction in a Long-Term Rodent Model of Critical Illness.

Critical illness encompasses a wide spectrum of life-threatening clinical conditions requiring intensive care. Our objective was to evaluate cognitive, inflammatory and cellular metabolism alterations in the central nervous system in an animal model of critical illness induced by zymosan. For this Wistar rats that were divided into Sham and zymosan. Zymozan was administered once intraperitoneally (30 g/100 g body weight) diluted in mineral oil. The animals were submitted to behavioral tests of octagonal maze, inhibitory avoidance and elevated plus maze. Brain structures (cortex, prefrontal and hippocampus) were removed at 24 h, 4, 7 and 15 days after zymosan administration for analysis of cytokine levels (TNF-α, IL-1b, IL-6 and IL-10), oxidative damage and oxygen consumption. Zymosan-treated animals presented mild cognitive impairment both in aversive (inhibitory avoidance) and non-aversive (octagonal maze) tasks by day 15. However, they did not show increase in anxiety (elevated-plus maze). The first neurochemical alteration found was an increase in brain pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) at day 4th in the hippocampus. In cortex, a late (7 and 15 days) increase in TNF-α was also noted, while the anti-inflammatory cytokine IL-10 decrease from 4 to 15 days. Oxygen consumption was decreased in the hippocampus and pre-frontal, but not cortex, only at 7 days. Additionally, it was observed a late (15 days) increase in oxidative damage parameters. This characterization of brain dysfunction in rodent model of critical illness reproduces some of the alterations reported in humans such neuropsychiatric disorders, especially depression, memory loss and cognitive changes and can add to the nowadays used models.

Chronic critical illness in polytrauma. Results of the Spanish trauma in ICU registry.

PURPOSE: Chronic critical illness after trauma injury has not been fully evaluated, and there is little evidence in this regard. We aim to describe the prevalence and risk factors of chronic critical illness (CCI) in trauma patients admitted to the intensive care unit. MATERIAL AND METHODS: Retrospective observational multicenter study (Spanish Registry of Trauma in ICU (RETRAUCI)). Period March 2015 to December 2019. Trauma patients admitted to the ICU, who survived the first 48 h, were included. Chronic critical illness (CCI) was considered as the need for mechanical ventilation for a period greater than 14 days and/or placement of a tracheostomy. The main outcomes measures were prevalence and risk factors of CCI after trauma. RESULTS: 1290/9213 (14%) patients developed CCI. These patients were older (51.2 ± 19.4 vs 49 ± 18.9); p < .01) and predominantly male (79.9%). They presented a higher proportion of infectious complications (81.3% vs 12.7%; p < .01) and multiple organ dysfunction syndrome (MODS) (27.02% vs 5.19%; p < .01). CCI patients required longer stays in the ICU and had higher ICU and overall in-hospital mortality. Age, injury severity score, head injury, infectious complications, and development of MODS were independent predictors of CCI. CONCLUSION: CCI in trauma is a prevalent entity in our series. Early identification could facilitate specific interventions to change the trajectory of this process.

Outcomes of prolonged intensive care and rehabilitation at a specialized multidisciplinary center in Sweden.

BACKGROUND: Specialized clinics may improve the outcome for patients with prolonged intensive care stays. Admission may depend on diagnosis, need of respiratory support and more. We report the results from a Swedish specialized center with a multidisciplinary team approach to continued intensive care and simultaneous rehabilitation regardless of patients' primary diagnosis or ventilator need. METHODS: All patients admitted and discharged from 2015 to 2018 were included. Demographics, diagnoses, ventilatory support requirement, discharge destination and survival were retrieved from the center´s quality registry. RESULTS: A total of 181 patients, mean age 61 ± 16 years, 64% men, were analyzed. A neurological diagnosis was the cause for hospitalization in 46% of patients. Of the 55 patients admitted to the center for weaning from mechanical ventilation, 89% were successfully weaned within a median of 25 (interquartile range (IQR) 16-45) days. Decannulation was intended in 117 patients of which 90% were successful within a median of 25 (IQR 13-43) days. Readmission to intensive care was 4%. Most patients were discharged to their home or to rehabilitation clinics with a lower level of care. In-clinic mortality was 3%. Survival beyond 1 and 2 years after discharge was 79% and 70%, respectively. CONCLUSION: Patients with prolonged intensive care and complex medical needs treated at a specialized center in Sweden had weaning and decannulation rates comparable to or better than previously reported. Mortality was low, and most patients were discharged home or for further rehabilitation. This was achieved with a multidisciplinary team approach to continued intensive care and simultaneous rehabilitation.

Actionable processes of care important to patients and family who experienced a prolonged intensive care unit stay: Qualitative interview study.

AIM: To use positive deviance to identify actionable processes of care that may improve outcomes and experience from the perspectives of prolonged intensive care unit (ICU) stay survivors and family members. DESIGN: Prospective qualitative interview study in two geographically distant settings: Canada (2018/19) and the United Kingdom (2019/20). METHODS: Patient and family participant inclusion criteria comprised: aged over 18 years, ICU stay in last 2 years of over 7 days, able to recall ICU stay and provided informed consent. We conducted semi-structured in-person or telephone interviews. Data were analysed using a positive deviance approach. RESULTS: We recruited 29 participants (15 Canadian; 14 UK). Of these, 11 were survivors of prolonged ICU stay and 18 family members. We identified 22 actionable processes (16 common to Canadian and UK participants, 4 Canadian only and 2 UK only). We grouped processes under three themes: physical and functional recovery (nine processes), patient psychological well-being (seven processes) and family relations (six processes). Most commonly identified physical/functional processes were regular physiotherapy, and fundamental hygiene and elimination care. For patient psychological well-being: normalizing the environment and routines, and alleviating boredom and loneliness. For family relations: proactive communication, flexible family visiting and presence with facilities for family. Our positive deviance analysis approach revealed that incorporation of these actionable processes into clinical practice was the exception as opposed to the norm perceived driven by individual acts of kindness and empathy as opposed to standardized processes. CONCLUSION: Actionable processes of care important to prolonged ICU stay survivors and family members differ from those frequently used in ICU quality improvement (QI) tools. IMPACT: Our study emphasizes the need to develop QI tools that standardize delivery of actionable processes important to patients and families experiencing a prolonged ICU stay. As the largest healthcare professional group, nurses can play an essential role in leading this.

Health-related expectations of the chronically critically ill: a multi-perspective qualitative study.

BACKGROUND: Those who survive critical illness only to become chronically critically ill (CCI) experience a high symptom burden, repeat episodes of illness exacerbation, communication barriers, and poor health outcomes. Yet, it is unclear how CCI individuals and their family understand their health and the importance of prognostic information following hospitalization. The research purpose was to examine expectations about health and disease prognosis of CCI residents in long-term care from the perspectives of the CCI themselves and their family members, as well as to describe healthcare provider (HCP) interpretations of, and reactions to, these health-related expectations. METHODS: In this qualitative interpretive descriptive study, conducted in British Columbia, Canada, 38 semi-structured interviews were conducted (6 CCI residents, 11 family members, and 21 HCPs) and inductively analyzed using thematic and constant comparative techniques. RESULTS: There was divergence in CCI resident, family and HCP expectations about health and the importance of disease prognosis, which contributed to conflict. CCI residents and family viewed conflict with HCPs in relation to their day-to-day care needs, while HCPs viewed this as arising from the unrealistically high expectations of residents and family. The CCI residents and family focussed on the importance of maintaining hope, and the HCPs highlighted the complexity of end-of-life decisions in conjunction with the high expectations and hopes of family. CONCLUSIONS: The emotional and ongoing process of formulating health-related expectations points to the need for future research to inform the development and/or adapting of existing communication, psychosocial and health services interventions to ease the burden experienced by those who are CCI.