Critical Care Bulletin: December-Jan 2022/3

 

Auto-antibodies against type I IFNs in > 10% of critically ill COVID-19 patients: a prospective multicentre study

 

by Romain Arrestier, Paul Bastard, Thibaut Belmondo, Guillaume Voiriot, Tomas Urbina, Charles-Edouard Luyt, Adrian Gervais, Lucy Bizien, Lauriane Segaux, Mariem Ben Ahmed, Raphaël Bellaïche, Taï Pham, Zakaria Ait-Hamou, Damien Roux, Raphael Clere-Jehl, Elie Azoulay…

 

Annals of Intensive Care volume 12, Article number: 121 (2022)

Background

Auto-antibodies (auto-Abs) neutralizing type I interferons (IFN) have been found in about 15% of critical cases COVID-19 pneumonia and less than 1% of mild or asymptomatic cases. Determining whether auto-Abs influence presentation and outcome of critically ill COVID-19 patients could lead to specific therapeutic interventions. Our objectives were to compare the severity at admission and the mortality of patients hospitalized for critical COVID-19 in ICU with versus without auto-Abs.

Results

We conducted a prospective multicentre cohort study including patients admitted in 11 intensive care units (ICUs) from Great Paris area hospitals with proven SARS-CoV-2 infection and acute respiratory failure. 925 critically ill COVID-19 patients were included. Auto-Abs neutralizing type I IFN-α2, β and/or ω were found in 96 patients (10.3%). Demographics and comorbidities did not differ between patients with versus without auto-Abs. At ICU admission, Auto-Abs positive patients required a higher FiO2 (100% (70–100) vs. 90% (60–100), p = 0.01), but were not different in other characteristics. Mortality at day 28 was not different between patients with and without auto-Abs (18.7 vs. 23.7%, p = 0.279). In multivariable analysis, 28-day mortality was associated with age (adjusted odds ratio (aOR) = 1.06 [1.04–1.08], p < 0.001), SOFA score (aOR = 1.18 [1.12–1.23], p < 0.001) and immunosuppression (aOR = 1.82 [1.1–3.0], p = 0.02), but not with the presence of auto-Abs (aOR = 0.69 [0.38–1.26], p = 0.23).

Conclusions

In ICU patients, auto-Abs against type I IFNs were found in at least 10% of patients with critical COVID-19 pneumonia. They were not associated with day 28 mortality.

 

 

Frailty is a stronger predictor of death in younger intensive care patients than in older patients: a prospective observational study

 

by Lina De Geer, Mats Fredrikson and Michelle S. Chew 

 

Annals of Intensive Care volume 12, Article number: 120 (2022) 

 

Background

While frailty is a known predictor of adverse outcomes in older patients, its effect in younger populations is unknown. This prospective observational study was conducted in a tertiary-level mixed ICU to assess the impact of frailty on long-term survival in intensive care patients of different ages.

Methods

Data on premorbid frailty (Clinical Frailty Score; CFS), severity of illness (the Simplified Acute Physiology Score, third version; SAPS3), limitations of care and outcome were collected in 817 adult ICU patients. Hazard ratios (HR) for death within 180 days after ICU admission were calculated. Unadjusted and adjusted analyses were used to evaluate the association of frailty with outcome in different age groups.

Results

Patients were classified into predefined age groups (18–49 years (n = 241), 50–64 (n = 188), 65–79 (n = 311) and 80 years or older (n = 77)). The proportion of frail (CFS ≥ 5) patients was 41% (n = 333) in the overall population and increased with each age strata (n = 46 (19%) vs. n = 67 (36%) vs. n = 174 (56%) vs. n = 46 (60%), P < 0.05). Frail patients had higher SAPS3, more treatment restrictions and higher ICU mortality. Frailty was associated with an increased risk of 180-day mortality in all age groups (HR 5.7 (95% CI 2.8–11.4), P < 0.05; 8.0 (4.0–16.2), P < 0.05; 4.1 (2.2–6.6), P < 0.05; 2.4 (1.1–5.0), P = 0.02). The effect remained significant after adjustment for SAPS3, comorbidity and limitations of treatment only in patients aged 50–64 (2.1 (1.1–3.1), P < 0.05).

Conclusions

Premorbid frailty is common in ICU patients of all ages and was found in 55% of patients aged under 64 years. Frailty was independently associated with mortality only among middle-aged patients, where the risk of death was increased twofold. Our study supports the use of frailty assessment in identifying younger ICU patients at a higher risk of death.

 

 

 

 

Effect of high-flow oxygen versus T-piece ventilation strategies during spontaneous breathing trials on weaning failure among patients receiving mechanical ventilation: a randomized controlled trial

by Hong Yeul Lee, Jinwoo Lee and Sang-Min Lee 

 

Critical Care volume 26, Article number: 402 (2022)

 

Background

A spontaneous breathing trial (SBT) is used to determine whether patients are ready for extubation, but the best method for choosing the SBT strategy remains controversial. We investigated the effect of high-flow oxygen versus T-piece ventilation strategies during SBT on rates of weaning failure among patients receiving mechanical ventilation.

Methods

This randomized clinical trial was conducted from June 2019 through January 2022 among patients receiving mechanical ventilation for ≥ 12 h who fulfilled the weaning readiness criteria at a single-center medical intensive care unit. Patients were randomized to undergo either T-piece SBT or high-flow oxygen SBT. The primary outcome was weaning failure on day 2, and the secondary outcomes were weaning failure on day 7, ICU and hospital length of stay, and ICU and in-hospital morality.

Results

Of 108 patients (mean age, 67.0 ± 11.1 years; 64.8% men), 54 received T-piece SBT and 54 received high-flow oxygen SBT. Weaning failure on day 2 occurred in 5 patients (9.3%) in the T-piece group and 3 patients (5.6%) in the high-flow group (difference, 3.7% [95% CI, − 6.1–13.6]; p = 0.713). Weaning failure on day 7 occurred in 13 patients (24.1%) in the T-piece group and 7 patients (13.0%) in the high-flow group (difference, 11.1% [95% CI, − 3.4–25.6]; p = 0.215). A post hoc subgroup analysis showed that high-flow oxygen SBT was significantly associated with a lower rate of weaning failure on day 7 (OR, 0.17 [95% CI, 0.04–0.78]) among those patients intubated because of respiratory failure (p for interaction = 0.020). The ICU and hospital length of stay and mortality rates did not differ significantly between the two groups. During the study, no serious adverse events were recorded.

Conclusions

Among patients receiving mechanical ventilation, high-flow oxygen SBT did not significantly reduce the risk of weaning failure compared with T-piece SBT. However, the study may have been underpowered to detect a clinically important treatment effect for the comparison of high-flow oxygen SBT versus T-piece SBT, and a higher percentage of patients with simple weaning and a lower weaning failure rate than expected should be considered when interpreting the findings.

 

Mechanical ventilation variables associated with high pulmonary artery pressures in ARDS patients: a post hoc analysis

 

by Joseph R. Riddell, Benjamin J. Jones, Bruno M. Fernandes, Daniel J. Law, Jackie A. Cooper and Matt P. Wise 

 

Critical Care volume 26, Article number: 396 (2022)

 

Background

The relationship between indices of mechanical ventilation and pulmonary artery pressures remains ill-defined in ARDS. As our understanding of mechanical ventilation has progressed, there is now a greater appreciation of the impact of high driving pressures and mechanical power in perpetuating lung injury. However, the relationship between the newer derived indices of mechanical ventilation and pulmonary artery pressure is unclear. We performed a post hoc analysis of the Fluid and Catheters Treatment Trial (FACTT) trial to investigate the associations between mechanical ventilation indices in ARDS patients and the prevalence of pulmonary hypertension. This may help elucidate future clinical targets for more, right ventricular protective, mechanical ventilation strategies.

Methods

We performed a post hoc analysis of the FACTT database to identify ARDS patients who had a pulmonary artery catheter (PAC) inserted and pulmonary artery pressure readings recorded. We excluded any patient with a PAC inserted who was spontaneously breathing, as driving pressure and mechanical power are not validated in this cohort. Three independent analyses were performed: a univariate analysis, to assess for associations between mPAP and mechanical ventilation parameters using Pearson correlation coefficients, a multivariate analysis, to assess for independent associations with mPAP using a multiple regression model according to Akaike’s information criteria and finally an analysis for nonlinearity, using the best-fitting model according to the Bayesian information criterion (BIC) from linear, quadratic, fractional polynomial and restricted cubic spline models.

Results

All the ventilation parameters demonstrated a significant correlation with mPAP, except tidal volume (once adjusted for respiratory rate) in the univariate analysis. The multivariate analysis demonstrated that the blood pH level, P/F ratio, PaCO2 level, mean airway pressure and the mechanical power indexed to compliance were independently associated with mPAP. In the final nonlinear analysis, associations did not differ from linearity except for 4 variables for which the fractional polynomial was the best-fitting model. These were mechanical power (p = 0.01 compared to the linear model), respiratory rate (p = 0.04), peak pressure (p = 0.03) and mean airway pressure (p = 0.01). Two nonlinear variables associated with mPAP were assessed in more detail, respiratory rate and mechanical power. Inflexion points at a respiratory rate of 16.8 cycles per minute and a mechanical power of 8.8 J/min were demonstrated.

Conclusions

The associations identified between mPAP and mechanical ventilation variables in this analysis would suggest that classical ARDS lung protective strategies, including low tidal volume ventilation and permissive hypercapnia, may negatively impact the management of the subset of ARDS patients with associated right ventricular dysfunction or ACP. Additionally, respiratory rates above 17 cycles per minute show an incremental increase in mPAP. Therefore, increases in tidal volume (within the limitation of driving pressure < 18 cmH20) may represent a more right ventricular protective way to control CO2 and pH.

 

 

 Impact of Prone Position in COVID-19 Patients on Extracorporeal Membrane Oxygenation*

 

by Massart, Nicolas; Guervilly, Christophe; Mansour, Alexandre; Porto, Alizée; Flécher, Erwan; Esvan, Maxime; Fougerou, Claire; Fillâtre, Pierre; Duburcq, Thibault; Lebreton, Guillaume; Para, Marylou; Stephan, François; Hraiech, Sami; Ross, James T.; Schmidt, Matthieu; Vincentelli, André; Nesseler, Nicolas; for the Extracorporeal Membrane Oxygenation for Respiratory Failure and/or Heart failure related to Severe Acute Respiratory Syndrome Coronavirus 2 (ECMOSARS) Investigators 

 

Critical Care Medicine 51(1):p 36-46, January 2023

 

OBJECTIVES: 

Prone positioning and venovenous extracorporeal membrane oxygenation (ECMO) are both useful interventions in acute respiratory distress syndrome (ARDS). Combining the two therapies is feasible and safe, but the effectiveness is not known. Our objective was to evaluate the potential survival benefit of prone positioning in venovenous ECMO patients cannulated for COVID-19–related ARDS.

DESIGN: 

Retrospective analysis of a multicenter cohort.

PATIENTS: 

Patients on venovenous ECMO who tested positive for severe acute respiratory syndrome coronavirus 2 by reverse transcriptase polymerase chain reaction or with a diagnosis on chest CT were eligible.

INTERVENTIONS: 

None.

MEASUREMENTS AND MAIN RESULTS: 

All patients on venovenous ECMO for respiratory failure in whom prone position status while on ECMO and in-hospital mortality were known were included. Of 647 patients in 41 centers, 517 were included. Median age was 55 (47–61), 78% were male and 95% were proned before cannulation. After cannulation, 364 patients (70%) were proned and 153 (30%) remained in the supine position for the whole ECMO run. There were 194 (53%) and 92 (60%) deaths in the prone and the supine groups, respectively. Prone position on ECMO was independently associated with lower in-hospital mortality (odds ratio = 0.49 [0.29–0.84]; p = 0.010). In 153 propensity score-matched pairs, mortality rate was 49.7% in the prone position group versus 60.1% in the supine position group (p = 0.085). Considering only patients alive at decannulation, propensity-matched proned patients had a significantly lower mortality rate (22.4% vs 37.8%; p = 0.029) than nonproned patients.

CONCLUSIONS: 

Prone position may be beneficial in patients supported by venovenous ECMO for COVID-19–related ARDS but more data are needed to draw definitive conclusions.

 

 

 

Score-based prediction model for severe vitamin D deficiency in patients with critical illness: development and validation

 

by Yu-Ting Kuo, Li-Kuo Kuo, Chung-Wei Chen, Kuo-Ching Yuan, Chun-Hsien Fu, Ching-Tang Chiu, Yu-Chang Yeh, Jen-Hao Liu and Ming-Chieh Shih 

 

Critical Care volume 26, Article number: 394 (2022)

 

Background

Severe vitamin D deficiency (SVDD) dramatically increases the risks of mortality, infections, and many other diseases. Studies have reported higher prevalence of vitamin D deficiency in patients with critical illness than general population. This multicenter retrospective cohort study develops and validates a score-based model for predicting SVDD in patients with critical illness.

Methods

A total of 662 patients with critical illness were enrolled between October 2017 and July 2020. SVDD was defined as a serum 25(OH)D level of < 12 ng/mL (or 30 nmol/L). The data were divided into a derivation cohort and a validation cohort on the basis of date of enrollment. Multivariable logistic regression (MLR) was performed on the derivation cohort to generate a predictive model for SVDD. Additionally, a score-based calculator (the SVDD score) was designed on the basis of the MLR model. The model’s performance and calibration were tested using the validation cohort.

Results

The prevalence of SVDD was 16.3% and 21.7% in the derivation and validation cohorts, respectively. The MLR model consisted of eight predictors that were then included in the SVDD score. The SVDD score had an area under the receiver operating characteristic curve of 0.848 [95% confidence interval (CI) 0.781–0.914] and an area under the precision recall curve of 0.619 (95% CI 0.577–0.669) in the validation cohort.

Conclusions

This study developed a simple score-based model for predicting SVDD in patients with critical illness.

 

 

Isoflurane vs. propofol for sedation in invasively ventilated patients with acute hypoxemic respiratory failure: an a priori hypothesis substudy of a randomized controlled trial

 

by Tobias Becher, Andreas Meiser, Ulf Guenther, Martin Bellgardt, Jan Wallenborn, Klaus Kogelmann, Hendrik Bracht, Andreas Falthauser, Jonas Nilsson, Peter Sackey and Patrick Kellner 

 

Annals of Intensive Care volume 12, Article number: 116 (2022) 

 

Background

Acute hypoxemic respiratory failure (AHRF) is a leading concern in critically ill patients. Experimental and clinical data suggest that early sedation with volatile anesthestics may improve arterial oxygenation and reduce the plasma and alveolar levels of markers of alveolar epithelial injury and of proinflammatory cytokines.

Methods

An a priori hypothesis substudy of a multicenter randomized controlled trial (The Sedaconda trial, EUDRA CT Number 2016-004551-67). In the Sedaconda trial, 301 patients on invasive mechanical ventilation were randomized to 48 h of sedation with isoflurane or propofol in a 1:1 ratio. For the present substudy, patients with a ratio of arterial pressure of oxygen (PaO2) to inspired fraction of oxygen (FiO2), PaO2/FiO2, of ≤ 300 mmHg at baseline were included (n = 162). The primary endpoint was the change in PaO2/FiO2 between baseline and the end of study sedation. A subgroup analysis in patients with PaO2/FiO2 ≤ 200 mmHg was performed (n = 82).

Results

Between baseline and the end of study sedation (48 h), oxygenation improved to a similar extent in the isoflurane vs. the propofol group (isoflurane: 199 ± 58 to 219 ± 76 mmHg (n = 70), propofol: 202 ± 62 to 236 ± 77 mmHg (n = 89); p = 0.185). On day seven after randomization, PaO2/FiO2 was 210 ± 79 mmHg in the isoflurane group (n = 41) and 185 ± 87 mmHg in the propofol group (n = 44; p = 0.411). In the subgroup of patients with PaO2/FiO2 ≤ 200 mmHg, PaO2/FiO2 increase between baseline and end of study sedation was 152 ± 33 to 186 ± 54 mmHg for isoflurane (n = 37), and 150 ± 38 to 214 ± 85 mmHg for propofol (n = 45; p = 0.029). On day seven, PaO2/FiO2 was 198 ± 69 mmHg in patients randomized to isoflurane (n = 20) and 174 ± 106 mmHg in patients randomized to propofol (n = 20; p = 0.933). Both for the whole study population and for the subgroup with PaO2/FiO2 ≤ 200 mmHg, no significant between-group differences were observed for PaCO2, pH and tidal volume as well as 30-day mortality and ventilator-free days alive.

Conclusions

In patients with AHRF, inhaled sedation with isoflurane for a duration of up to 48 h did not lead to improved oxygenation in comparison to intravenous sedation with propofol.

Trial registration The main study was registered in the European Medicines Agency’s EU Clinical Trial register (EudraCT), 2016-004551-67, before including the first patient. The present substudy was registered at German Clinical Trials Register (DRKS, ID: DRKS00018959) on January 7th, 2020, before opening the main study data base and obtaining access to study results.

 

 

 

A multicentric prospective observational study of diagnosis and prognosis features in ICU mesenteric ischemia: the DIAGOMI study

 

by Simon Bourcier, Guillaume Ulmann, Matthieu Jamme, Guillaume Savary, Marine Paul, Sarah Benghanem, Jean-Rémi Lavillegrand, Matthieu Schmidt, Charles-Edouard Luyt, Eric Maury, Alain Combes, Frédéric Pène, Nathalie Neveux and Alain Cariou 

 

Annals of Intensive Care volume 12, Article number: 113 (2022)

 

Background

Non-occlusive mesenteric ischemia (NOMI) is a challenging diagnosis and is associated with extremely high mortality in critically ill patients, particularly due to delayed diagnosis and when complicated by intestinal necrosis. Plasma citrulline and intestinal-fatty acid binding protein (I-FABP) have been proposed as potential biomarkers, but have never been studied prospectively in this setting. We aimed to investigate diagnostic features, the accuracy of plasma citrulline and I-FABP to diagnose NOMI and intestinal necrosis as well as prognosis.

Methods

We conducted a prospective observational study in 3 tertiary ICU centers in consecutive patients with NOMI suspicion defined by at least two inclusion criteria among: new-onset or worsening circulatory failure, gastrointestinal dysfunction, biological signs and CT-scan signs of mesenteric ischemia. Diagnosis features and outcomes were compared according to NOMI, intestinal necrosis or ruled out diagnosis using stringent classification criteria.

Results

Diagnosis of NOMI was suspected in 61 patients and confirmed for 33 patients, with intestinal necrosis occurring in 27 patients. Clinical digestive signs, routine laboratory results and CT signs of mesenteric ischemia did not discriminate intestinal necrosis from ischemia without necrosis. Plasma I-FABP was significantly increased in presence of intestinal necrosis (AUC 0.83 [0.70–0.96]). A threshold of 3114 pg/mL showed a sensitivity of 70% [50–86], specificity of 85% [55–98], a negative predictive value of 58% [36–93] and a positive predictive value 90% [67–96] for intestinal necrosis diagnosis. When intestinal necrosis was present, surgical resection was significantly associated with ICU survival (38.5%), whereas no patient survived without necrosis resection (HR = 0.31 [0.12–0.75], p = 0.01).

Conclusion

In critically ill patients with NOMI, intestinal necrosis was associated with extremely high mortality, and increased survival when necrosis resection was performed. Elevated plasma I-FABP was associated with the diagnosis of intestinal necrosis. Further studies are needed to investigate plasma I-FABP and citrulline performance in less severe forms of NOMI.

 

 

 

ARDS: hidden perils of an overburdened diagnosis

 

by Martin J. Tobin 

 

Critical Care volume 26, Article number: 392 (2022)

 

A diagnosis of ARDS serves as a pretext for several perilous clinical practices. Clinical trials demonstrated that tidal volume 12 ml/kg increases patient mortality, but 6 ml/kg has not proven superior to 11 ml/kg or anything in between. Present guidelines recommend 4 ml/kg, which foments severe air hunger, leading to prescription of hazardous (yet ineffective) sedatives, narcotics and paralytic agents. Inappropriate lowering of tidal volume also fosters double triggering, which promotes alveolar overdistention and lung injury. Successive panels have devoted considerable energy to developing a more precise definition of ARDS to homogenize the recruitment of patients into clinical trials. Each of three pillars of the prevailing Berlin definition is extremely flimsy and the source of confusion and unscientific practices. For doctors at the bedside, none of the revisions have enhanced patient care over that using the original 1967 description of Ashbaugh and colleagues. Bedside doctors are better advised to diagnose ARDS on the basis of pattern recognition and instead concentrate their vigilance on resolving the numerous hidden dangers that follow inevitably once a diagnosis has been made…

 

Continuous bladder urinary oxygen tension as a new tool to monitor medullary oxygenation in the critically ill

 

by Raymond T. Hu, Yugeesh R. Lankadeva, Fumitake Yanase, Eduardo A. Osawa, Roger G. Evans and Rinaldo Bellomo 

 

Critical Care volume 26, Article number: 389 (2022) 

 

Acute kidney injury (AKI) is common in the critically ill. Inadequate renal medullary tissue oxygenation has been linked to its pathogenesis. Moreover, renal medullary tissue hypoxia can be detected before biochemical evidence of AKI in large mammalian models of critical illness. This justifies medullary hypoxia as a pathophysiological biomarker for early detection of impending AKI, thereby providing an opportunity to avert its evolution. Evidence from both animal and human studies supports the view that non-invasively measured bladder urinary oxygen tension (PuO2) can provide a reliable estimate of renal medullary tissue oxygen tension (tPO2), which can only be measured invasively. Furthermore, therapies that modify medullary tPO2 produce corresponding changes in bladder PuO2. Clinical studies have shown that bladder PuO2 correlates with cardiac output, and that it increases in response to elevated cardiopulmonary bypass (CPB) flow and mean arterial pressure. Clinical observational studies in patients undergoing cardiac surgery involving CPB have shown that bladder PuO2 has prognostic value for subsequent AKI. Thus, continuous bladder PuO2 holds promise as a new clinical tool for monitoring the adequacy of renal medullary oxygenation, with its implications for the recognition and prevention of medullary hypoxia and thus AKI.

 

Association of sepsis-induced cardiomyopathy and mortality: a systematic review and meta-analysis

 

by Yu-Min Lin, Mei-Chuan Lee, Han Siong Toh, Wei-Ting Chang, Sih-Yao Chen, Fang-Hsiu Kuo, Hsin-Ju Tang, Yi-Ming Hua, Dongmei Wei, Jesus Melgarejo, Zhen-Yu Zhang and Chia-Te Liao 

 

Annals of Intensive Care volume 12, Article number: 112 (2022) 

 

Background

The implication of  (SIC) to prognosis is controversial, and its association with mortality at different stages remains unclear. We conducted a systematic review and meta-analysis to understand the association between SIC and mortality in septic patients.

Methods

We searched and appraised observational studies regarding the mortality related to SIC among septic patients in PubMed and Embase from inception until 8 July 2021. Outcomes comprised in-hospital and 1-month mortality. We adopted the random-effects model to examine the mortality risk ratio in patients with and without SIC. Meta-regression, subgroup, and sensitivity analyses were applied to examine the outcome’s heterogeneity.

Results

Our results, including 20 studies and 4,410 septic patients, demonstrated that SIC was non-statistically associated with increased in-hospital mortality, compared to non-SIC (RR 1.28, [0.96–1.71]; p = 0.09), but the association was statistically significant in patients with the hospital stay lengths longer than 10 days (RR 1.40, [1.02–1.93]; p = 0.04). Besides, SIC was significantly associated with a higher risk of 1-month mortality (RR 1.47, [1.17–1.86]; p < 0.01). Among SIC patients, right ventricular dysfunction was significantly associated with increased 1-month mortality (RR 1.72, [1.27–2.34]; p < 0.01), while left ventricular dysfunction was not (RR 1.33, [0.87–2.02]; p = 0.18).

Conclusions

With higher in-hospital mortality in those hospitalized longer than 10 days and 1-month mortality, our findings imply that SIC might continue influencing the host’s system even after recovery from cardiomyopathy. Besides, right ventricular dysfunction might play a crucial role in SIC-related mortality, and timely biventricular assessment is vital in managing septic patients.