Critical Care Bulletin - March 2023

 

Incidence of near-death experiences in patients surviving a prolonged critical illness and their long-term impact: a prospective observational study

 

by Anne-Françoise Rousseau, Laurence Dams, Quentin Massart, Laila Choquer, Héléna Cassol, Steven Laureys, Benoit Misset, Nadia Dardenne, Olivia Gosseries and Charlotte Martial 

 

Critical Care volume 27, Article number: 76 (2023)

 

Background

So far, the few prospective studies on near-death experience (NDE) were carried out only in intensive care unit (ICU) patients with homogeneous aetiologies, such as cardiac arrest or trauma survivors. The aims of this 1-year prospective and monocentric study were to investigate the incidence of NDE in ICU survivors (all aetiologies) as well as factors that may affect its frequency, and to assess quality of life up to 1 year after enrolment.

Methods

We enrolled adults with a prolonged ICU stay (> 7 days). During the first 7 days after discharge, all eligible patients were assessed in a face-to-face interview for NDE using the Greyson NDE scale, dissociative experiences using the Dissociative Experience Scale, and spirituality beliefs using the WHOQOL-SRPB. Medical parameters were prospectively collected. At 1-year after inclusion, patients were contacted by phone to measure quality of life using the EuroQol five-dimensional questionnaire.

Results

Out of the 126 included patients, 19 patients (15%) reported having experienced a NDE as identified by the Greyson NDE scale (i.e. cut-off score ≥ 7/32). In univariate analyses, mechanical ventilation, sedation, analgesia, reason for admission, primary organ dysfunction, dissociative and spiritual propensities were associated with the emergence of NDE. In multivariate logistic regression analysis, only the dissociative and spiritual propensity strongly predicted the emergence of NDE. One year later (n = 61), the NDE was not significantly associated with quality of life.

Conclusions

The recall of NDE is not so rare in the ICU. In our cohort, cognitive and spiritual factors outweighed medical parameters as predictors of the emergence of NDE.

 

Oxygenation thresholds for invasive ventilation in hypoxemic respiratory failure: a target trial emulation in two cohorts

 

by Christopher J. Yarnell, Federico Angriman, Bruno L. Ferreyro, Kuan Liu, Harm Jan De Grooth, Lisa Burry, Laveena Munshi, Sangeeta Mehta, Leo Celi, Paul Elbers, Patrick Thoral, Laurent Brochard, Hannah Wunsch, Robert A. Fowler, Lillian Sung and George Tomlinson 

 

Critical Care volume 27, Article number: 67 (2023)

 

Background

The optimal thresholds for the initiation of invasive ventilation in patients with hypoxemic respiratory failure are unknown. Using the saturation-to-inspired oxygen ratio (SF), we compared lower versus higher hypoxemia severity thresholds for initiating invasive ventilation.

Methods

This target trial emulation included patients from the Medical Information Mart for Intensive Care (MIMIC-IV, 2008–2019) and the Amsterdam University Medical Centers (AmsterdamUMCdb, 2003–2016) databases admitted to intensive care and receiving inspired oxygen fraction ≥ 0.4 via non-rebreather mask, noninvasive ventilation, or high-flow nasal cannula. We compared the effect of using invasive ventilation initiation thresholds of SF < 110, < 98, and < 88 on 28-day mortality. MIMIC-IV was used for the primary analysis and AmsterdamUMCdb for the secondary analysis. We obtained posterior means and 95% credible intervals (CrI) with nonparametric Bayesian G-computation.

Results

We studied 3,357 patients in the primary analysis. For invasive ventilation initiation thresholds SF < 110, SF < 98, and SF < 88, the predicted 28-day probabilities of invasive ventilation were 72%, 47%, and 19%. Predicted 28-day mortality was lowest with threshold SF < 110 (22.2%, CrI 19.2 to 25.0), compared to SF < 98 (absolute risk increase 1.6%, CrI 0.6 to 2.6) or SF < 88 (absolute risk increase 3.5%, CrI 1.4 to 5.4). In the secondary analysis (1,279 patients), the predicted 28-day probability of invasive ventilation was 50% for initiation threshold SF < 110, 28% for SF < 98, and 19% for SF < 88. In contrast with the primary analysis, predicted mortality was highest with threshold SF < 110 (14.6%, CrI 7.7 to 22.3), compared to SF < 98 (absolute risk decrease 0.5%, CrI 0.0 to 0.9) or SF < 88 (absolute risk decrease 1.9%, CrI 0.9 to 2.8).

Conclusion

Initiating invasive ventilation at lower hypoxemia severity will increase the rate of invasive ventilation, but this can either increase or decrease the expected mortality, with the direction of effect likely depending on baseline mortality risk and clinical context.

 

Fluid balance control in critically ill patients: results from POINCARE-2 stepped wedge cluster-randomized trial

by Pierre-Edouard Bollaert, Alexandra Monnier, Francis Schneider, Laurent Argaud, Julio Badie, Claire Charpentier, Ferhat Meziani, Michel Bemer, Jean-Pierre Quenot, Marie Buzzi, Hervé Outin, Cédric Bruel, Laurent Ziegler, Sébastien Gibot, Jean-Marc Virion, Camille Alleyrat… 

Critical Care volume 27, Article number: 66 (2023)

Background

In critically ill patients, positive fluid balance is associated with excessive mortality. The POINCARE-2 trial aimed to assess the effectiveness of a fluid balance control strategy on mortality in critically ill patients.

Methods

POINCARE-2 was a stepped wedge cluster open-label randomized controlled trial. We recruited critically ill patients in twelve volunteering intensive care units from nine French hospitals. Eligible patients were ≥ 18 years old, under mechanical ventilation, admitted to one of the 12 recruiting units for > 48 and ≤ 72 h, and had an expected length of stay after inclusion > 24 h. Recruitment started on May 2016 and ended on May 2019. Of 10,272 patients screened, 1361 met the inclusion criteria and 1353 completed follow-up. The POINCARE-2 strategy consisted of a daily weight-driven restriction of fluid intake, diuretics administration, and ultrafiltration in case of renal replacement therapy between Day 2 and Day 14 after admission. The primary outcome was 60-day all-cause mortality. We considered intention-to-treat analyses in cluster-randomized analyses (CRA) and in randomized before-and-after analyses (RBAA).

Results

A total of 433 (643) patients in the strategy group and 472 (718) in the control group were included in the CRA (RBAA). In the CRA, mean (SD) age was 63.7 (14.1) versus 65.7 (14.3) years, and mean (SD) weight at admission was 78.5 (20.0) versus 79.4 (23.5) kg. A total of 129 (160) patients died in the strategy (control) group. Sixty-day mortality did not differ between groups [30.5%, 95% confidence interval (CI) 26.2–34.8 vs. 33.9%, 95% CI 29.6–38.2, p = 0.26]. Among safety outcomes, only hypernatremia was more frequent in the strategy group (5.3% vs. 2.3%, p = 0.01). The RBAA led to similar results.

Conclusion

The POINCARE-2 conservative strategy did not reduce mortality in critically ill patients. However, due to open-label and stepped wedge design, intention-to-treat analyses might not reflect actual exposure to this strategy, and further analyses might be required before completely discarding it.

 

Association of systolic, diastolic, mean, and pulse pressure with morbidity and mortality in septic ICU patients: a nationwide observational study

by Ashish K. Khanna, Takahiro Kinoshita, Annamalai Natarajan, Emma Schwager, Dustin D. Linn, Junzi Dong, Erina Ghosh, Francesco Vicario and Kamal Maheshwari 

Annals of Intensive Care volume 13, Article number: 9 (2023)

 

Background

Intensivists target different blood pressure component values to manage intensive care unit (ICU) patients with sepsis. We aimed to evaluate the relationship between individual blood pressure components and organ dysfunction in critically ill septic patients.

Methods

In this retrospective observational study, we evaluated 77,328 septic patients in 364 ICUs in the eICU Research Institute database. Primary exposure was the lowest cumulative value of each component; mean, systolic, diastolic, and pulse pressure, sustained for at least 120 min during ICU stay. Primary outcome was ICU mortality and secondary outcomes were composite outcomes of acute kidney injury or death and myocardial injury or death during ICU stay. Multivariable logistic regression spline and threshold regression adjusting for potential confounders were conducted to evaluate associations between exposures and outcomes. Sensitivity analysis was conducted in 4211 patients with septic shock.

Results

Lower values of all blood pressures components were associated with a higher risk of ICU mortality. Estimated change-points for the risk of ICU mortality were 69 mmHg for mean, 100 mmHg for systolic, 60 mmHg for diastolic, and 57 mmHg for pulse pressure. The strength of association between blood pressure components and ICU mortality as determined by slopes of threshold regression were mean (− 0.13), systolic (− 0.11), diastolic (− 0.09), and pulse pressure (− 0.05). Equivalent non-linear associations between blood pressure components and ICU mortality were confirmed in septic shock patients. We observed a similar relationship between blood pressure components and secondary outcomes.

Conclusion

Blood pressure component association with ICU mortality is the strongest for mean followed by systolic, diastolic, and weakest for pulse pressure. Critical care teams should continue to follow MAP-based resuscitation, though exploratory analysis focusing on blood pressure components in different sepsis phenotypes in critically ill ICU patients is needed.

 

Prevalence of long-term decision regret and associated risk factors in a large cohort of ICU surrogate decision makers

by Sarah K. Andersen, Rachel A. Butler, Chung-Chou H. Chang, Robert Arnold, Derek C. Angus and Douglas B. White 

Critical Care volume 27, Article number: 61 (2023)

 

Background

Whether surrogate decision makers regret decisions about the use of life support for incapacitated, critically ill patients remain uncertain. We sought to determine the prevalence of decision regret among surrogates of adult ICU patients and identify factors that influence regret.

Methods

We conducted a secondary analysis of data from the PARTNER 2 trial, which tested a family support intervention for surrogates of critically ill adults. At 6-month follow-up, surrogates rated their regret about life support decisions using the Decision Regret Scale (DRS), scored from 0 to 100, with higher scores indicating more regret. We used multiple linear regression to identify covariates associated with decision regret based on a psychological construct of regret. We constructed two models using the full cohort; model 1 included patient outcomes; model 2 focused on covariates known at the time of ICU decision-making. Subgroup analyses were also conducted based on patient survival status at hospital discharge and 6-month follow-up.

Results

748 of 848 surrogates had complete DRS data. The median (IQR) DRS score was 15 (0, 25). Overall, 54% reported mild regret (DRS 5–25), 19% moderate-strong regret (DRS 30–100), and 27% no regret (DRS 0). Poor patient outcome at 6 months (death or severe functional dependence) was associated with more regret in model 1 (β 10.1; 95% C.I. 3.2, 17.0). In model 2, palliative care consultation (3.0; 0.1, 5.9), limitations in life support (LS) prior to death (6.3; 3.1, 9.4) and surrogate black race (6.3; 0.3, 12.3) were associated with more regret. Other modulators of regret in subgroup analyses included surrogate age and education level, surrogate-patient relationship, death in hospital (compared to the post-discharge period), and code status at time of ICU admission.

Conclusions

One in five ICU surrogate decision makers experience moderate to strong regret about life support decisions in ICU. Poor patient outcomes are linked to more regret. Decisions to limit life support prior to patient death may also increase regret. Future studies are needed to understand how regret relates to decision quality and how to lessen lasting regret.

 

Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study

 

Intensive Care Medicine volume 49, pages178–190 (2023)

 

Purpose

In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials.

Methods

We carried out a prospective international cohort study of adult patients (≥ 18 years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021.

Results

2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp. (20.3%), Escherichia coli (15.8%), and Pseudomonas spp. (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) was present in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24 h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alive from hospital by day-28.

Conclusions

HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes.

 

ICU patients with infectious complications after abdominopelvic surgery: Is thoracic CT in addition to abdominal CT helpful?

 

by Heiner Nebelung, Natalie Wotschel, Hanns-Christoph Held, Johanna Kirchberg, Jürgen Weitz, Christoph Georg Radosa, Michael Laniado, Ralf-Thorsten Hoffmann and Verena Plodeck 

 

Annals of Intensive Care volume 13, Article number: 6 (2023) 

 

Background

The aim of this study was to assess the usefulness of adding thoracic CT to abdominal CT in intensive care unit (ICU) patients with signs of infection after abdominopelvic surgery.

Methods

143 thoracoabdominal CTs of ICU patients with signs of infection after abdominopelvic surgery were retrospectively reviewed for thoracic pathologies. It was determined if pathologic findings were visible only on thoracic CT above the diaphragmatic dome or also on abdominal CT up to the diaphragmatic dome. All thoracic pathologies visible only above the diaphragmatic dome were retrospectively analyzed by an ICU physician in terms of clinical relevance. Diagnostic and therapeutic efficacy of thoracic CT were assessed with regard to an infectious focus and to other pathologic findings.

Results

297 pathologic thoracic findings were recorded. 26 of the 297 findings could only be detected on images obtained above the diaphragmatic dome (in 23 of 143 CTs). A change in patient management was initiated due to only one of the 26 supradiaphragmatic findings. Diagnostic efficacy of thoracic CT in addition to abdominal CT to identify an infectious focus was 3.5% (95%-CI: 0.5–6.5%) and therapeutic efficacy was 0.7% (95%-CI: 0–2.1%). With regard to all pathologic thoracic findings, diagnostic efficacy was 16.1% (95%-CI: 10.1–22.1%) and therapeutic efficacy remained at 0.7%.

Conclusions

Additional thoracic CT to detect an infectious focus in ICU patients after abdominopelvic surgery leads to identification of the focus in only 3.5% and to changes in patient management in only 0.7%. Other relevant findings are more common (16.1%), but very rarely affect patient management.

 

Point-of-care diagnosis and monitoring of fibrinolysis resistance in the critically ill: results from a feasibility study

by Lucy A. Coupland, David J. Rabbolini, Jonathan G. Schoenecker, Philip J. Crispin, Jennene J. Miller, Tony Ghent, Robert L. Medcalf and Anders E. Aneman

Critical Care volume 27, Article number: 55 (2023)

Background

Fibrinolysisis is essential for vascular blood flow maintenance and is triggered by endothelial and platelet release of tissue plasminogen activator (t-PA). In certain critical conditions, e.g. sepsis, acute respiratory failure (ARF) and trauma, the fibrinolytic response is reduced and may lead to widespread thrombosis and multi-organ failure. The mechanisms underpinning fibrinolysis resistance include reduced t-PA expression and/or release, reduced t-PA and/or plasmin effect due to elevated inhibitor levels, increased consumption and/or clearance. This study in critically ill patients with fibrinolysis resistance aimed to evaluate the ability of t-PA and plasminogen supplementation to restore fibrinolysis with assessment using point-of-care ClotPro viscoelastic testing (VET).

Methods

In prospective, observational studies, whole-blood ClotPro VET evaluation was carried out in 105 critically ill patients. In 32 of 58 patients identified as fibrinolysis-resistant (clot lysis time > 300 s on the TPA-test: tissue factor activated coagulation with t-PA accelerated fibrinolysis), consecutive experimental whole-blood VET was carried out with repeat TPA-tests spiked with additional t-PA and/or plasminogen and the effect on lysis time determined. In an interventional study in a patient with ARF and fibrinolysis resistance, the impact of a 24 h intravenous low-dose alteplase infusion on coagulation and fibrinolysis was prospectively monitored using standard ClotPro VET.

Results

Distinct response groups emerged in the ex vivo experimental VET, with increased fibrinolysis observed following supplementation with (i) t-PA only or (ii) plasminogen and t-PA. A baseline TPA-test lysis time of > 1000 s was associated with the latter group. In the interventional study, a gradual reduction (25%) in serial TPA-test lysis times was observed during the 24 h low-dose alteplase infusion.

Conclusions

ClotPro viscoelastic testing, the associated TPA-test and the novel experimental assays may be utilised to (i) investigate the potential mechanisms of fibrinolysis resistance, (ii) guide corrective treatment and (iii) monitor in real-time the treatment effect. Such a precision medicine and personalised treatment approach to the management of fibrinolysis resistance has the potential to increase treatment benefit, while minimising adverse events in critically ill patients.

 

Rationale for sequential extracorporeal therapy (SET) in sepsis

 

by Claudio Ronco, Lakhmir Chawla, Faeq Husain-Syed and John A. Kellum 

 

Critical Care volume 27, Article number: 50 (2023)

 

Abstract

Sepsis and septic shock remain drivers for morbidity and mortality in critical illness. The clinical picture of patients presenting with these syndromes evolves rapidly and may be characterised by: (a) microbial host invasion, (b) establishment of an infection focus, (c) opsonisation of bacterial products (e.g. lipopolysaccharide), (d) recognition of pathogens resulting in an immune response, (e) cellular and humoral effects of circulating pathogen and pathogen products, (f) immunodysregulation and endocrine effects of cytokines, (g) endothelial and organ damage, and (h) organ crosstalk and multiple organ dysfunction. Each step may be a potential target for a specific therapeutic approach. At various stages, extracorporeal therapies may target circulating molecules for removal. In sequence, we could consider: (a) pathogen removal from the circulation with affinity binders and cartridges (specific), (b) circulating endotoxin removal by haemoperfusion with polymyxin B adsorbers (specific), (c) cytokine removal by haemoperfusion with sorbent cartridges or adsorbing membranes (non-specific), (d) extracorporeal organ support with different techniques for respiratory and cardiac support (CO2 removal or extracorporeal membrane oxygenation), and renal support (haemofiltration, haemodialysis, or ultrafiltration). The sequence of events and the use of different techniques at different points for specific targets will likely require trials with endpoints other than mortality. Instead, the primary objectives should be to achieve the desired action by using extracorporeal therapy at a specific point.

 

COVID-19 does not influence functional status after ARDS therapy

 

by Alice Bernard, Lina Maria Serna-Higuita, Peter Martus, Valbona Mirakaj, Michael Koeppen, Alexander Zarbock, Gernot Marx, Christian Putensen, Peter Rosenberger and Helene Anna Haeberle 

 

Critical Care volume 27, Article number: 48 (2023) 

 

Rationale

Health-related quality of life after surviving acute respiratory distress syndrome has come into focus in recent years, especially during the coronavirus disease 2019 pandemic.

Objectives

A total of 144 patients with acute respiratory distress syndrome caused by COVID-19 or of other origin were recruited in a randomized multicenter trial.

Methods

Clinical data during intensive care treatment and data up to 180 days after study inclusion were collected. Changes in the Sequential Organ Failure Assessment score were used to quantify disease severity. Disability was assessed using the Barthel index on days 1, 28, 90, and 180.

Measurements

Mortality rate and morbidity after 180 days were compared between patients with and without COVID-19. Independent risk factors associated with high disability were identified using a binary logistic regression.

Main results

The SOFA score at day 5 was an independent risk factor for high disability in both groups, and score dynamic within the first 5 days significantly impacted disability in the non-COVID group. Mortality after 180 days and impairment measured by the Barthel index did not differ between patients with and without COVID-19.

Conclusions

Resolution of organ dysfunction within the first 5 days significantly impacts long-term morbidity. Acute respiratory distress syndrome caused by COVID-19 was not associated with increased mortality or morbidity.

 

Dead space ventilation-related indices: bedside tools to evaluate the ventilation and perfusion relationship in patients with acute respiratory distress syndrome

 

by Mingjia Zheng 

 

Critical Care volume 27, Article number: 46 (2023) 

 

Abstract

Cumulative evidence has demonstrated that the ventilatory ratio closely correlates with mortality in acute respiratory distress syndrome (ARDS), and a primary feature in coronavirus disease 2019 (COVID-19)-ARDS is increased dead space that has been reported recently. Thus, new attention has been given to this group of dead space ventilation-related indices, such as physiological dead space fraction, ventilatory ratio, and end-tidal-to-arterial PCO2 ratio, which, albeit distinctive, are all global indices with which to assess the relationship between ventilation and perfusion. These parameters have already been applied to positive end expiratory pressure titration, prediction of responses to the prone position and the field of extracorporeal life support for patients suffering from ARDS. Dead space ventilation-related indices remain hampered by several deflects; notwithstanding, for this catastrophic syndrome, they may facilitate better stratifications and identifications of subphenotypes, thereby providing therapy tailored to individual needs.

 

Does tidal volume challenge improve the feasibility of pulse pressure variation in patients mechanically ventilated at low tidal volumes? A systematic review and meta-analysis

 

by Xiaoying Wang, Shuai Liu, Ju Gao, Yang Zhang and Tianfeng Huang 

 

Critical Care volume 27, Article number: 45 (2023)

 

Background

Pulse pressure variation (PPV) has been widely used in hemodynamic assessment. Nevertheless, PPV is limited in low tidal volume ventilation. We conducted this systematic review and meta-analysis to evaluate whether the tidal volume challenge (TVC) could improve the feasibility of PPV in patients ventilated at low tidal volumes.

Methods

PubMed, Embase and Cochrane Library inception to October 2022 were screened for diagnostic researches relevant to the predictability of PPV change after TVC in low tidal volume ventilatory patients. Summary receiving operating characteristic curve (SROC), pooled sensitivity and specificity were calculated. Subgroup analyses were conducted for possible influential factors of TVC.

Results

Ten studies with a total of 429 patients and 457 measurements were included for analysis. The predictive performance of PPV was significantly lower than PPV change after TVC in low tidal volume, with mean area under the receiving operating characteristic curve (AUROC) of 0.69 ± 0.13 versus 0.89 ± 0.10. The SROC of PPV change yielded an area under the curve of 0.96 (95% CI 0.94, 0.97), with overall pooled sensitivity and specificity of 0.92 (95% CI 0.83, 0.96) and 0.88 (95% CI 0.76, 0.94). Mean and median cutoff value of the absolute change of PPV (△PPV) were 2.4% and 2%, and that of the percentage change of PPV (△PPV%) were 25% and 22.5%. SROC of PPV change in ICU group, supine or semi-recumbent position group, lung compliance less than 30 cm H2O group, moderate positive end-expiratory pressure (PEEP) group and measurements devices without transpulmonary thermodilution group yielded 0.95 (95%0.93, 0.97), 0.95 (95% CI 0.92, 0.96), 0.96 (95% CI 0.94, 0.97), 0.95 (95% CI 0.93, 0.97) and 0.94 (95% CI 0.92, 0.96) separately. The lowest AUROCs of PPV change were 0.59 (95% CI 0.31, 0.88) in prone position and 0.73 (95% CI 0.60, 0.84) in patients with spontaneous breathing activity.

Conclusions

TVC is capable to help PPV overcome limitations in low tidal volume ventilation, wherever in ICU or surgery. The accuracy of TVC is not influenced by reduced lung compliance, moderate PEEP and measurement tools, but TVC should be cautious applied in prone position and patients with spontaneous breathing activity.