Critical Care Bulletin - September 2024

 

Innate immune response in acute critical illness: a narrative review

Annals of Intensive Care volume 14, Article number: 137 (2024) Published: 04 September 2024

Background

Activation of innate immunity is a first line of host defense during acute critical illness (ACI) that aims to contain injury and avoid tissue damages. Aberrant activation of innate immunity may also participate in the occurrence of organ failures during critical illness. This review aims to provide a narrative overview of recent advances in the field of innate immunity in critical illness, and to consider future potential therapeutic strategies.

Main text

Understanding the underlying biological concepts supporting therapeutic strategies modulating immune response is essential in decision-making. We will develop the multiple facets of innate immune response, especially its cellular aspects, and its interaction with other defense mechanisms. We will first describe the pathophysiological mechanisms of initiation of innate immune response and its implication during ACI. We will then develop the amplification of innate immunity mediated by multiple effectors. Our review will mainly focus on myeloid and lymphoid cellular effectors, the major actors involved in innate immune-mediated organ failure. We will third discuss the interaction and integration of innate immune response in a global view of host defense, thus considering interaction with non-immune cells through immunothrombosis, immunometabolism and long-term reprogramming via trained immunity. The last part of this review will focus on the specificities of the immune response in children and the older population.

Conclusions

Recent understanding of the innate immune response integrates immunity in a highly dynamic global vision of host response. A better knowledge of the implicated mechanisms and their tissue-compartmentalization allows to characterize the individual immune profile, and one day eventually, to develop individualized bench-to-bedside immunomodulation approaches as an adjuvant resuscitation strategy.

 

Assessment of fluid responsiveness using pulse pressure variation, stroke volume variation, plethysmographic variability index, central venous pressure, and inferior vena cava variation in patients undergoing mechanical ventilation: a systematic review and meta-analysis

Critical Care volume 28, Article number: 289 (2024) Published: 31 August 2024

Importance

Maneuvers assessing fluid responsiveness before an intravascular volume expansion may limit useless fluid administration, which in turn may improve outcomes.

Objective

To describe maneuvers for assessing fluid responsiveness in mechanically ventilated patients.

Registration

The protocol was registered at PROSPERO: CRD42019146781.

Information sources and search

PubMed, EMBASE, CINAHL, SCOPUS, and Web of Science were search from inception to 08/08/2023.

Study selection and data collection

Prospective and intervention studies were selected.

Statistical analysis

Data for each maneuver were reported individually and data from the five most employed maneuvers were aggregated. A traditional and a Bayesian meta-analysis approach were performed.

Results

A total of 69 studies, encompassing 3185 fluid challenges and 2711 patients were analyzed. The prevalence of fluid responsiveness was 49.9%. Pulse pressure variation (PPV) was studied in 40 studies, mean threshold with 95% confidence intervals (95% CI) = 11.5 (10.5–12.4)%, and area under the receiver operating characteristics curve (AUC) with 95% CI was 0.87 (0.84–0.90). Stroke volume variation (SVV) was studied in 24 studies, mean threshold with 95% CI = 12.1 (10.9–13.3)%, and AUC with 95% CI was 0.87 (0.84–0.91). The plethysmographic variability index (PVI) was studied in 17 studies, mean threshold = 13.8 (12.3–15.3)%, and AUC was 0.88 (0.82–0.94). Central venous pressure (CVP) was studied in 12 studies, mean threshold with 95% CI = 9.0 (7.7–10.1) mmHg, and AUC with 95% CI was 0.77 (0.69–0.87). Inferior vena cava variation (∆IVC) was studied in 8 studies, mean threshold = 15.4 (13.3–17.6)%, and AUC with 95% CI was 0.83 (0.78–0.89).

Conclusions

Fluid responsiveness can be reliably assessed in adult patients under mechanical ventilation. Among the five maneuvers compared in predicting fluid responsiveness, PPV, SVV, and PVI were superior to CVP and ∆IVC. However, there is no data supporting any of the above mentioned as being the best maneuver. Additionally, other well-established tests, such as the passive leg raising test, end-expiratory occlusion test, and tidal volume challenge, are also reliable.

 

Factors associated with cancer treatment resumption after ICU stay in patients with solid tumors

Annals of Intensive Care volume 14, Article number: 135 (2024) Published: 31 August 2024

Background

Post-intensive care syndrome could be responsible for inability to receive proper cancer treatment after ICU stay in patients with solid tumors (ST). Our purpose was to determine the factors associated with cancer treatment resumption and the impact of cancer treatment on the outcome of patients with ST after ICU stay.

Methods

We conducted a retrospective study including all patients with ST admitted to the ICU between 2014 and 2019 in a French University-affiliated Hospital.

Results

A total of 219 patients were included. Median SAPS II at ICU admission was 44.0 [IQR 32.8, 66.3]. Among the 136 patients who survived the ICU stay, 81 (59.6%) received cancer treatment after ICU discharge. There was an important increase in patients with poor performance status (PS) of 3 or 4 after ICU stay (16.2% at admission vs. 44.5% of patients who survived), with significant PS decline following the ICU stay (median difference − 1.5, 95% confidence interval [-1.5-1.0], p < 0.001). The difference between the PS after and before ICU stay (delta PS) was independently associated with inability to receive cancer treatment (Odds ratio OR 0.34, 95%CI 0.18–0.56, p value < 0.001) and with 1-year mortality in patients who survived at ICU discharge (Hazard ratio HR 1.76, 95%CI 1.34–2.31, p value < 0.001). PS before ICU stay (OR 3.73, 95%IC 2.01–7.82, p value < 0.001) and length of stay (OR 1.23, 95%CI 1.06–1.49, p value 0.018) were independently associated with poor PS after ICU stay. Survival rates at ICU discharge, at 1 and 3 years were 62.3% (n = 136), 27.3% (n = 59) and 17.1% (n = 37), respectively. The median survival for patients who resumed cancer treatment after ICU stay was 771 days (95%CI 376–1058), compared to 29 days (95%CI 15–49) for those who did not resume treatment (p < 0.001).

Conclusion

Delta PS, before and after ICU stay, stands out as a critical determinant of cancer treatment resumption and survival after ICU stay. Multidisciplinary intervention to improve the general condition of these patients, in ICU and after ICU stay, may improve access to cancer treatment and long-term survival.

 

The ventilator of the future: key principles and unmet needs

Critical Care volume 28, Article number: 284 (2024) Published: 29 August 2024

Abstract

Persistent shortcomings of invasive positive pressure ventilation make it less than an ideal intervention. Over the course of more than seven decades, clinical experience and scientific investigation have helped define its range of hazards and limitations. Apart from compromised airway clearance and lower airway contamination imposed by endotracheal intubation, the primary hazards inherent to positive pressure ventilation may be considered in three broad categories: hemodynamic impairment, potential for ventilation-induced lung injury, and impairment of the respiratory muscle pump. To optimize care delivery, it is crucial for monitoring and machine outputs to integrate information with the potential to impact the underlying requirements of the patient and/or responses of the cardiopulmonary system to ventilatory interventions. Trending analysis, timely interventions, and closer communication with the caregiver would limit adverse clinical trajectories. Judging from the rapid progress of recent years, we are encouraged to think that insights from physiologic research and emerging technological capability may eventually address important aspects of current deficiencies.

 

How are Long-Covid, Post-Sepsis-Syndrome and Post-Intensive-Care-Syndrome related? A conceptional approach based on the current research literature

Critical Care volume 28, Article number: 283 (2024)  Published: 29 August 2024

Abstract

Long-Covid (LC), Post-Sepsis-Syndrome (PSS) and Post-Intensive-Care-Syndrome (PICS) show remarkable overlaps in their clinical presentation. Nevertheless, it is unclear if they are distinct syndromes, which may co-occur in the same patient, or if they are three different labels to describe similar symptoms, assigned on the basis on patient history and professional perspective of the treating physician. Therefore, we reviewed the current literature on the relation between LC, PSS and PICS. To date, the three syndromes cannot reliably be distinguished due similarities in clinical presentation as they share the cognitive, psychological and physical impairments with only different probabilities of occurrence and a heterogeneity in individual expression. The diagnosis is furthermore hindered by a lack of specific diagnostic tools. It can be concluded that survivors after COVID-19 sepsis likely have more frequent and more severe consequences than patients with milder COVID-19 courses, and that are some COVID-19-specific sequelae, e.g. an increased risk for venous thromboembolism in the 30 days after the acute disease, which occur less often after sepsis of other causes. Patients may profit from leveraging synergies from PICS, PSS and LC treatment as well as from experiences gained from infection-associated chronic conditions in general. Disentangling molecular pathomechanisms may enable future targeted therapies that go beyond symptomatic treatment.

 

Development of a biomarker prediction model for post-trauma multiple organ failure/dysfunction syndrome based on the blood transcriptome

Annals of Intensive Care volume 14, Article number: 134 (2024) Published: 28 August 2024

Background

Multiple organ failure/dysfunction syndrome (MOF/MODS) is a major cause of mortality and morbidity among severe trauma patients. Current clinical practices entail monitoring physiological measurements and applying clinical score systems to diagnose its onset. Instead, we aimed to develop an early prediction model for MOF outcome evaluated soon after traumatic injury by performing machine learning analysis of genome-wide transcriptome data from blood samples drawn within 24 h of traumatic injury. We then compared its performance to baseline injury severity scores and detection of infections.

Methods

Buffy coat transcriptome and linked clinical datasets from blunt trauma patients from the Inflammation and the Host Response to Injury Study (“Glue Grant”) multi-center cohort were used. According to the inclusion/exclusion criteria, 141 adult (age ≥ 16 years old) blunt trauma patients (excluding penetrating) with early buffy coat (≤ 24 h since trauma injury) samples were analyzed, with 58 MOF-cases and 83 non-cases. We applied the Least Absolute Shrinkage and Selection Operator (LASSO) and eXtreme Gradient Boosting (XGBoost) algorithms to select features and develop models for MOF early outcome prediction.

Results

The LASSO model included 18 transcripts (AUROC [95% CI]: 0.938 [0.890–0.987] (training) and 0.833 [0.699–0.967] (test)), and the XGBoost model included 41 transcripts (0.999 [0.997–1.000] (training) and 0.907 [0.816–0.998] (test)). There were 16 overlapping transcripts comparing the two panels (0.935 [0.884–0.985] (training) and 0.836 [0.703–0.968] (test)). The biomarker models notably outperformed models based on injury severity scores and sex, which we found to be significantly associated with MOF (APACHEII + sex—0.649 [0.537–0.762] (training) and 0.493 [0.301–0.685] (test); ISS + sex—0.630 [0.516–0.744] (training) and 0.482 [0.293–0.670] (test); NISS + sex—0.651 [0.540–0.763] (training) and 0.525 [0.335–0.714] (test)).

Conclusions

The accurate assessment of MOF from blood samples immediately after trauma is expected to aid in improving clinical decision-making and may contribute to reduced morbidity, mortality and healthcare costs. Moreover, understanding the molecular mechanisms involving the transcripts identified as important for MOF prediction may eventually aid in developing novel interventions.

 

Role of age as eligibility criterion for ECMO in patients with ARDS: meta-regression analysis

Critical Care volume 28, Article number: 278 (2024) Published: 27 August 2024

Background

Age as an eligibility criterion for V-V ECMO is widely debated and varies among healthcare institutions. We examined how age relates to mortality in patients undergoing V-V ECMO for ARDS.

Methods

Systematic review and meta-regression of clinical studies published between 2015 and June 2024. Studies involving at least 6 ARDS patients treated with V-V ECMO, with specific data on ICU and/or hospital mortality and patient age were included. The search strategy was executed in PubMed, limited to English-language. COVID-19 and non-COVID-19 populations were analyzed separately. Meta-regressions of mortality outcomes on age were performed using gender, BMI, SAPS II, APACHE II, Charlson comorbidity index or SOFA as covariates.

Results

In non-COVID ARDS, the meta-regression of 173 studies with 56,257 participants showed a significant positive association between mean age and ICU/hospital mortality. In COVID-19 ARDS, a significant relationship between mean age and ICU mortality, but not hospital mortality, was found in 103 studies with 21,255 participants. Sensitivity analyses confirmed these findings, highlighting a linear relationship between age and mortality in both groups. For each additional year of mean age, ICU mortality increased by 1.2% in non-COVID ARDS and 1.9% in COVID ARDS.

Conclusions

The relationship between age and ICU mortality is linear and shows no inflection point. Consequently, no age cut-off can be recommended for determining patient eligibility for V-V ECMO.

 

Derivation and external validation of predictive models for invasive mechanical ventilation in intensive care unit patients with COVID-19

Annals of Intensive Care volume 14, Article number: 129 (2024) Published: 21 August 2024

Background

This study aimed to develop prognostic models for predicting the need for invasive mechanical ventilation (IMV) in intensive care unit (ICU) patients with COVID-19 and compare their performance with the Respiratory rate-OXygenation (ROX) index.

Methods

A retrospective cohort study was conducted using data collected between March 2020 and August 2021 at three hospitals in Rio de Janeiro, Brazil. ICU patients aged 18 years and older with a diagnosis of COVID-19 were screened. The exclusion criteria were patients who received IMV within the first 24 h of ICU admission, pregnancy, clinical decision for minimal end-of-life care and missing primary outcome data. Clinical and laboratory variables were collected. Multiple logistic regression analysis was performed to select predictor variables. Models were based on the lowest Akaike Information Criteria (AIC) and lowest AIC with significant p values. Assessment of predictive performance was done for discrimination and calibration. Areas under the curves (AUC)s were compared using DeLong’s algorithm. Models were validated externally using an international database.

Results

Of 656 patients screened, 346 patients were included; 155 required IMV (44.8%), 191 did not (55.2%), and 207 patients were male (59.8%). According to the lowest AIC, arterial hypertension, diabetes mellitus, obesity, Sequential Organ Failure Assessment (SOFA) score, heart rate, respiratory rate, peripheral oxygen saturation (SpO2), temperature, respiratory effort signals, and leukocytes were identified as predictors of IMV at hospital admission. According to AIC with significant p values, SOFA score, SpO2, and respiratory effort signals were the best predictors of IMV; odds ratios (95% confidence interval): 1.46 (1.07–2.05), 0.81 (0.72–0.90), 9.13 (3.29–28.67), respectively. The ROX index at admission was lower in the IMV group than in the non-IMV group (7.3 [5.2–9.8] versus 9.6 [6.8–12.9], p < 0.001, respectively). In the external validation population, the area under the curve (AUC) of the ROX index was 0.683 (accuracy 63%), the AIC model showed an AUC of 0.703 (accuracy 69%), and the lowest AIC model with significant p values had an AUC of 0.725 (accuracy 79%).

Conclusions

In the development population of ICU patients with COVID-19, SOFA score, SpO2, and respiratory effort signals predicted the need for IMV better than the ROX index. In the external validation population, although the AUCs did not differ significantly, the accuracy was higher when using SOFA score, SpO2, and respiratory effort signals compared to the ROX index. This suggests that these variables may be more useful in predicting the need for IMV in ICU patients with COVID-19.

 

Long-term effects of flexible visitation in the intensive care unit on family members’ mental health: 12-month results from a randomized clinical trial

Intensive Care Medicine, Published: 22 August 2024

Purpose

The aim of this study was to assess the effects of flexible intensive care unit (ICU) visitation on the 1-year prevalence of post-traumatic stress, anxiety and depression symptoms among family members of critically ill patients.

Methods

This is a long-term outcome analysis of a cluster-crossover randomized clinical trial that evaluated a flexible visitation model in the ICU (12 h/day) compared to a restrictive visitation model (median 1.5 h/day) in 36 Brazilian ICUs. In this analysis, family members were assessed 12 months after patient discharge from the ICU for the following outcomes: post-traumatic stress symptoms measured by the Impact Event Scale-6 and anxiety and depression symptoms measured by the Hospital Anxiety and Depression Scale.

Results

A total of 519 family members were analyzed (288 in the flexible visitation group and 231 in the restrictive visitation group). Three-hundred sixty-nine (71.1%) were women, and the mean age was 46.6 years. Compared to family members in the restrictive visitation group, family members in the flexible visitation group had a significantly lower prevalence of post-traumatic stress symptoms (21% vs. 30.5%; adjusted prevalence ratio [aPR], 0.91; 95% confidence interval [CI] 0.85–0.98; p = 0.01). The prevalence of anxiety (28.9% vs. 33.2%; aPR 0.93; 95% CI 0.72–1.21; p = 0.59) and depression symptoms (19.2% vs. 25%; aPR, 0.78; 95% CI 0.60–1.02; p = 0.07) did not differ significantly between the groups.

Conclusion

Flexible ICU visitation, compared to the restrictive visitation, was associated with a significant reduction in the 1-year prevalence of post-traumatic stress symptoms in family members.

 

Early reapplication of prone position during venovenous ECMO for acute respiratory distress syndrome: a prospective observational study and propensity-matched analysis

by Rui Wang, Xiao Tang, Xuyan Li, Ying Li, Yalan Liu, Ting Li, Yu Zhao, Li Wang, Haichao Li, Meng Li, Hu Li, Zhaohui Tong and Bing Sun 

Annals of Intensive Care volume 14, Article number: 127 (2024) Published: 20 August 2024

Background

A combination of prone positioning (PP) and venovenous extracorporeal membrane oxygenation (VV-ECMO) is safe, feasible, and associated with potentially improved survival for severe acute respiratory distress syndrome (ARDS). However, whether ARDS patients, especially non-COVID-19 patients, placed in PP before VV-ECMO should continue PP after a VV-ECMO connection is unknown. This study aimed to test the hypothesis that early use of PP during VV-ECMO could increase the proportion of patients successfully weaned from ECMO support in severe ARDS patients who received PP before ECMO.

Methods

In this prospective observational study, patients with severe ARDS who were treated with VV-ECMO were divided into two groups: the prone group and the supine group, based on whether early PP was combined with VV-ECMO. The proportion of patients successfully weaned from VV-ECMO and 60-day mortality were analyzed before and after propensity score matching.

Results

A total of 165 patients were enrolled, 50 in the prone and 115 in the supine group. Thirty-two (64%) and 61 (53%) patients were successfully weaned from ECMO in the prone and the supine groups, respectively. The proportion of patients successfully weaned from VV-ECMO in the prone group tended to be higher, albeit not statistically significant. During PP, there was a significant increase in partial pressure of arterial oxygen (PaO2) without a change in ventilator or ECMO settings. Tidal impedance shifted significantly to the dorsal region, and lung ultrasound scores significantly decreased in the anterior and posterior regions. Forty-five propensity score-matched patients were included in each group. In this matched sample, the prone group had a higher proportion of patients successfully weaned from VV-ECMO (64.4% vs. 42.2%; P = 0.035) and lower 60-day mortality (37.8% vs. 60.0%; P = 0.035).

Conclusions

Patients with severe ARDS placed in PP before VV-ECMO should continue PP after VV-ECMO support. This approach could increase the probability of successful weaning from VV-ECMO.

 

Barriers to female leadership in intensive care medicine: insights from an ESICM NEXT & Diversity Monitoring Group Survey

by Silvia De Rosa, Stefan J. Schaller, Laura Galarza, Ricard Ferrer, Bairbre A. McNicholas, Max Bell, Julie Helms, Elie Azoulay and Antoine Vieillard-Baron 

Annals of Intensive Care volume 14, Article number: 126 (2024) Published: 19 August 2024

Background

The underrepresentation of women in leadership remains a pervasive issue, prompting a critical examination of support mechanisms within professional settings. Previous studies have identified challenges women face, ranging from limited visibility to barriers to career advancement. This survey aims to investigate perceptions regarding the effectiveness of women’s leadership programs, mentoring initiatives, and a specialized communication course. Particularly it specifically targets addressing the challenges encountered by professional women.

Methods

This multi-center, observational, international online survey was developed in partnership between ESICM NEXT and the ESICM Diversity and Inclusiveness Monitoring Group for Healthcare. Invitations to participate were distributed to both females and men through emails and social networks. Data were collected from April 1, 2023, through October 1, 2023.

Results

Out of 354 respondents, 90 were men (25.42%) and 264 were women (74.58%). Among them, 251 completed the survey, shedding light on the persistent challenges faced by women in leadership roles, with 10%-50% of respondents holding such positions. Women’s assertiveness is viewed differently, with 65% recognizing barriers such as harassment. Nearly half of the respondent’s experience interruptions in meetings. Only 47.4% receiving conference invitations, with just over half accepting them. A mere 12% spoke at ESICM conferences in the last three years, receiving limited support from directors and colleagues, indicating varied obstacles for female professionals. Encouraging family participation, reducing fees, providing childcare, and offering economic support can enhance conference involvement. Despite 55% applying for ESICM positions, barriers like mobbing, harassment, lack of financial support, childcare, and language barriers were reported. Only 14% had access to paid family leave, while 32% benefited from subsidized childcare. Participation in the Effective Communication Course on Career Advancement Goals and engagement in women’s leadership and mentoring programs could offer valuable insights and growth opportunities. Collaborating with Human Resources and leadership allies is crucial for overcoming barriers and promoting women’s career growth.

Conclusions

The urgency of addressing identified barriers to female leadership in intensive care medicine is underscored by the survey’s comprehensive insights. A multifaceted and intersectional approach, considering sexism, structural barriers, and targeted strategies, is essential.

 

Assessing palliative care practices in intensive care units and interpreting them using the lens of appropriate care concepts. An umbrella review

Intensive Care Medicine, Published: 14 August 2024

Purpose

Intensive care units (ICUs) have significant palliative care needs but lack a reliable care framework. This umbrella review addresses them by synthesising palliative care practices provided at end-of-life to critically ill patients and their families before, during, and after ICU admission.

Methods

Seven databases were systematically searched for systematic reviews, and the umbrella review was conducted according to the guidelines laid out by the Joanna Briggs Institute (JBI).

Results

Out of 3122 initial records identified, 40 systematic reviews were included in the synthesis. Six key themes were generated that reflect the palliative and end-of-life care practices in the ICUs and their outcomes. Effective communication and accurate prognostications enabled families to make informed decisions, cope with uncertainty, ease distress, and shorten ICU stays. Inter-team discussions and agreement on a plan are essential before discussing care goals. Recording care preferences prevents unnecessary end-of-life treatments. Exceptional end-of-life care should include symptom management, family support, hydration and nutrition optimisation, avoidance of unhelpful treatments, and bereavement support. Evaluating end-of-life care quality is critical and can be accomplished by seeking family feedback or conducting a survey.

Conclusion

This umbrella review encapsulates current palliative care practices in ICUs, influencing patient and family outcomes and providing insights into developing an appropriate care framework for critically ill patients needing end-of-life care and their families.

 

Sex matters: Is it time for a SOFA makeover?

by Emma Larsson 

Critical Care 28, Article number: 268 (2024) Published 8 August 2024

While sepsis affects individuals regardless of sex, emerging research has highlighted notable differences in how women and men experience, respond to, and recover from sepsis treated in intensive care units (ICU). These differences are influenced by a complex interplay of biological, hormonal, and sociocultural factors. As we explore sepsis management in ICU settings, it becomes evident that understanding the factors contributing to these sex-based variations is important for tailoring therapeutic approaches and improving overall patient outcomes. Moreover, for a nuanced interpretation of current evidence, it is worth noting the distinction between the terms gender and sex: gender refers to the socially constructed roles and behaviors that a given society considers appropriate, while sex pertains to biological characteristics...