The PRESERVE mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome

Purpose

This study was designed to identify factors associated with death by 6 months post-intensive care unit (ICU) discharge and to develop a practical mortality risk score for extracorporeal membrane oxygenation (ECMO)-treated acute respiratory distress syndrome (ARDS) patients. We also assessed long-term survivors’ health-related quality of life (HRQL), respiratory symptoms, and anxiety, depression and post-traumatic stress disorder (PTSD) frequencies.

Methods

Data from 140 ECMO-treated ARDS patients admitted to three French ICUs (2008–2012) were analyzed. ICU survivors contacted >6 months post-ICU discharge were assessed for HRQL, psychological and PTSD status.

Results

Main ARDS etiologies were bacterial (45 %), influenza A[H₁N₁] (26 %) and post-operative (17 %) pneumonias. Six months post-ICU discharge, 84 (60 %) patients were still alive. Based on multivariable logistic regression analysis, the PRESERVE (PRedicting dEath for SEvere ARDS on VV-ECMO) score (0–14 points) was constructed with eight pre-ECMO parameters, i.e. age, body mass index, immunocompromised status, prone positioning, days of mechanical ventilation, sepsis-related organ failure assessment, plateau pressure andpositive end-expiratory pressure. Six-month post-ECMO initiation cumulative probabilities of survival were 97, 79, 54 and 16 % for PRESERVE classes 0–2, 3–4, 5–6 and ≥7 (p < 0.001), respectively. HRQL evaluation in 80 % of the 6-month survivors revealed satisfactory mental health but persistent physical and emotional-related difficulties, with anxiety, depression or PTSD symptoms reported, by 34, 25 or 16 %, respectively.

Conclusions

The PRESERVE score might help ICU physicians select appropriate candidates for ECMO among severe ARDS patients. Future studies should also focus on physical and psychosocial rehabilitation that could lead to improved HRQL in this population.     

Plasma levels of the three endothelial-specific proteins von Willebrand factor, tissue factor pathway inhibitor, and thrombomodulin do not predict the development of acute respiratory distress syndrome

Objective: To determine if the plasma levels of three endothelial-specific proteins, von Willebrand factor (vWF), tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) may be useful in predicting the development of acute respiratory distress syndrome (ARDS).¶Design: Blood samples were obtained from normal healthy volunteers and on the first day from patients at risk for ARDS and those with ARDS. Daily sequential measurements of vWF and TFPI were performed in two patients.¶Setting: Normal subjects were employees at Saint Louis University Hospital, St. Louis, Missouri. Patients at risk and those with ARDS were patients admitted to the medical and surgical floors and the intensive care units at St. Louis University Hospital.¶Patients and participants: Plasma levels of vWF, TFPI and TM were measured in 27 normals, and on day 1 in 15 patients at risk for ARDS and 18 patients with ARDS from different etiologic factors.¶Measurements and results: Plasma levels of vWF were significantly elevated in the at-risk (p < 0.01) and ARDS group (p < 0.001) as compared to normals but did not differ significantly between the two groups (p > 0.05). Plasma levels of TFPI were not significantly different between the normal and the at-risk group (p > 0.05); however, they were significantly elevated in ARDS as compared with at-risk and normal groups (p < 0.001). Levels of TM were significantly increased in the at-risk group as compared to normals (p < 0.01) but were not significantly different from the ARDS group (p > 0.05). Eight patients at risk progressed to develop ARDS. A vWF level of > 300 % in patients at risk was 62 % sensitive and 71 % specific for predicting the development of ARDS with a positive predictive value of only 34 %. TFPI levels were normal in 7 of the 8 patients who developed ARDS. A TM level of > 100 ng/ml in patients at risk was 50 % sensitive and 57 % specific with a positive predictive value of merely 8 % for development of ARDS. There was no significant difference in the mean plasma levels of the three proteins on day 1 in patients at risk who developed ARDS as compared with those who did not develop ARDS. There was also no difference in mean plasma levels of the three proteins in patients with ARDS from sepsis as compared with ARDS from other etiologies. Plasma levels of vWF and TFPI correlated significantly.¶Conclusion: Plasma levels of vWF, TFPI and TM did not appear to serve as useful markers for predicting ARDS in patients at risk.     

ARDS in patients with thermal injury

Objective: To determine the time to onset of the adult respiratory distress syndrome (ARDS) in patients with thermal injury requiring mechanical ventilation. Secondarily, to consider the burn-related risk factors, demographics, incidence, and mortality for ARDS in this population.¶Design: Retrospective chart review; ARDS defined according to the American-European Consensus Conference and the Lung Injury Severity Score definitions.¶Setting: Regional, tertiary referral, adult burn unit in a university teaching hospital.¶Patients and participants: Patients with thermal injury requiring mechanical ventilation, admitted between 1 January 1991 and 28 February 1995.¶Interventions: None.¶Measurements and results: Of 469 consecutive admissions, 126 (26.9 %) received intubation and mechanical ventilation. ARDS was defined according to the American-European Consensus and Lung Injury Severity Score (score > 2.5) definitions. The mean time to onset of ARDS from admission to the burn unit was 6.9 ± 5.2 and 8.2 ± 10.7 days when defined by the American-European Consensus and Lung Injury Severity Score definitions respectively (p = 0.41). Of the intubated patients, 53.6 and 45.2 % developed ARDS according to the American-European Consensus and Lung Injury Severity Score definitions, respectively (p = 0.19). Using multivariate logistic analysis, only age proved to be an independent risk factor for the development of ARDS (p = 0.03), although there was a trend toward an increased incidence of inhalation injury in patients with ARDS. Mortality was not significantly greater (41.8 vs 32.2 %) in those with ARDS compared to those without (p = 0.27).¶Conclusions: According to the American-European Consensus Conference and the Lung Injury Severity Score definitions, ARDS is common in the adult burn population and has a delayed onset compared to most critical care populations. We found age to be a major predisposing factor for ARDS.     

Recovery from withdrawal of inhaled nitric oxide and kinetics of nitric oxide-induced inhibition of nitric oxide synthase activity in vitro

Objective: To examine the kinetics of successful nitric oxide (NO) withdrawal in vivo and in vitro.¶Design and setting: Prospective study in a university pediatric intensive care ward and research laboratory.¶Patients and materials: Nineteen patients with acute respiratory distress syndrome (ARDS) or persistent pulmonary hypertension of the newborn (PPHN). Primary porcine pulmonary artery cells in vitro.¶Interventions: NO inhalation and withdrawal in patients; exposure to NO donor sodium nitroprusside (SNP) and gaseous NO in vitro.¶Measurements and results: In patients: a slight, but significant, increase of oxygenation index (OI) from 4.57 ± 0.24 cmH₂O/torr (mean ± SEM) to 4.90 ± 0.26 cmH₂O/torr after withdrawal of NO (p < 0.001). Recovery of OI (4.43 ± 0.23 cmH₂O/torr) 30 min after weaning, a significant drop after 4 h (3.72 ± 0.17 cmH₂O/torr; p < 0.001), values restored after 12 h.¶In vitro: NO synthase (NOS) activity was significantly lower in SNP-incubated cells (20.0 ± 4.0 μm/min) than in control cells (37.6 ± 7.0 μm/min; p < 0.05). Thirty minutes after SNP withdrawal there was NOS activity of 35.8 ± 10.0 μm/min with a significant increase by 4 h (p < 0.05). No alteration of endothelial NOS (ENOS) mRNA expression by NO (Northern Blot).¶Conclusion: In patients there is a slight, but significant, reversible increase of OI after successful weaning from NO. In vitro, NO leads to a reversible decrease of ENOS activity on a post mRNA level, resembling clinical observations.     

Association of PEEP with two different inflation volumes in ARDS patients: effects on passive lung deflation and alveolar recruitment

Objective: To assess the effects of the association of positive end-expiratory pressure (PEEP) with different inflation volumes (V_T's) on passive lung deflation and alveolar recruitment in ARDS patients.¶Design: Clinical study using PEEP with two different V_T's and analyzing whether passive lung deflation and alveolar recruitment (Vrec) depend on end-inspired (EILV) or end-expired (EELV) lung volume in mechanically ventilated ARDS patients.¶Setting: Medical intensive care unit in a university hospital.¶Patients and participants: Six mechanically ventilated consecutive supine patients with ARDS.¶Interventions: Time-course of thoracic volume decay during passive expiration and Vrec were investigated in six ARDS patients ventilated on PEEP with baseline V_T (V_T,b) and 0.5V_T (0.5V_T,b), and on zero PEEP (ZEEP) with V_T,b. Time constants of the fast (τ ₁) and slow (τ ₂) emptying compartments, as well as resistances and elastances were also determined.¶Measurements and results: (a) the bi-exponential model best fitted the volume decay in all instances. The fast compartment was responsible for 84 ± 7 (0.5V_T,b) and 86 ± 5 % (V_T,b) on PEEP vs 81 ± 6 % (V_T,b) on ZEEP (P:ns) of the exhaled V_T, with τ ₁ of 0.50 ± 0.13 and 0.58 ± 0.17 s vs 0.35 ± 0.11 s, respectively; (b) only τ ₁ for V_T,b on PEEP differed significantly (P < 0.02) from the one on ZEEP, suggesting a slower initial emptying; (c) for the same PEEP, Vrec was higher with a higher volume (V_T,b) than at a lesser one (0.5V_T,b), reflecting the higher V_T.¶Conclusions: In mechanically ventilated ARDS patients: (a) the behavior of airway resistance seems to depend on the degree of the prevailing lung distension; (b) alveolar recruitment appears to be more important when higher tidal volumes are used during mechanical ventilation on PEEP; (c) PEEP changes the mechanical properties of the respiratory system fast-emptying compartment.     

Long-term physical impairments in survivors of COVID-19-associated ARDS compared with classic ARDS: A two-center study

PurposeThis work aimed to compare physical impairment in survivors of classic ARDS compared with COVID-19–associated ARDS (CARDS) survivors.Material and methodsThis is a prospective observational cohort study on 248 patients with CARDS and compared them with a historical cohort of 48 patients with classic ARDS. Physical performance was evaluated at 6 and 12 months after ICU discharge, using the Medical Research Council Scale (MRCss), 6-min walk test (6MWT), handgrip dynamometry (HGD), and fatigue severity score (FSS). We also assessed activities of daily living (ADLs) using the Barthel index.ResultsAt 6 months, patients with classic ARDS had lower HGD (estimated difference [ED]: 11.71 kg, p < 0.001; ED 31.9% of predicted value, p < 0.001), 6MWT distance (ED: 89.11 m, p < 0.001; ED 12.96% of predicted value, p = 0.032), and more frequent significant fatigue (OR 0.35, p = 0.046). At 12 months, patients with classic ARDS had lower HGD (ED: 9.08 kg, p = 0.0014; ED 25.9% of predicted value, p < 0.001) and no difference in terms of 6MWT and fatigue. At 12 months, patients with classic ARDS improved their MRCss (ED 2.50, p = 0.006) and HGD (ED: 4.13 kg, p = 0.002; ED 9.45% of predicted value, p = 0.005), while those with CARDS did not. Most patients in both groups regained independence in ADLs at 6 months.COVID-19 diagnosis was a significant independent predictor of better HGD (p < 0.0001) and 6MWT performance (p = 0.001), and lower prevalence of fatigue (p = 0.018).ConclusionsBoth classic ARDS and CARDS survivors experienced long-term impairments in physical functioning, confirming that post-intensive care syndrome remains a major legacy of critical illness. Surprisingly, however, persisting disability was more common in survivors of classic ARDS than in CARDS survivors. In fact, muscle strength measured with HGD was reduced in survivors of classic ARDS compared to CARDS patients at both 6 and 12 months. The 6MWT was reduced and fatigue was more common in classic ARDS compared to CARDS at 6 months but differences were no longer significant at 12 months. Most patients in both groups regained independent function in ADLs at 6 months.     

Volume-dependent compliance in ARDS: proposal of a new diagnostic concept

Objective: Adaptation of ventilator settings to the individual's respiratory system mechanics requires information about the pressure-volume relationship and the change of compliance which is dependent on inflated volume. Unfortunately, established methods of obtaining this information are invasive and time-consuming, and, therefore, not well suited for clinical routine. We propose a new standardized diagnostic concept based on the recently developed slice method. This multiple linear regression method (MLR) determines volume-dependent respiratory system compliance (C_SLICE) within the tidal volume (V_T) during ongoing mechanical ventilation. The impact of a ventilator strategy, recommended by a consensus conference, on the course of compliance within V_T was investigated in patients with the acute respiratory distress syndrome (ARDS) or acute lung injury (ALI).¶Design: Prospective observational study.¶Setting: Intensive care unit of a university hospital.¶Patients: 14 ARDS patients, 2 patients with ALI.¶Interventions: None.¶Measurements and results: After measurement of flow and airway pressure and calculation of tracheal pressure, C_SLICE was determined. The resulting course of C_SLICE within V_T was estimated using a mathematical algorithm. C_SLICE data were compared to those obtained by standard MLR. We found decreasing C_SLICE mainly in the upper part of V_T in all patients. In 7 patients, we found an additional increasing C_SLICE mainly in the lower part of V_T.¶Conclusions: C_SLICE was not constant in patients with ARDS/ALI whose lungs were ventilated according to consensus conference recommendations. The proposed diagnostic concept may serve as a new tool to obtain a standardized estimation of respiratory system compliance within V_T non-invasively without interfering with ongoing mechanical ventilation.     

Effects of prone position on alveolar recruitment and oxygenation in acute lung injury

Objective: To investigate the effects of prone position (PP) on alveolar recruitment and oxygenation in acute respiratory failure.¶Design: Prospective physiologic study.¶Setting: Medical ICU two in a university hospital.¶Patients: Twelve adult patients intubated and mechanically ventilated with medical primary acute lung injury/adult respiratory distress syndrome (ALI/ARDS) in whom PP was indicated.¶Measurements and results: We constructed the static inflation volume-pressure curves (V-P) of the respiratory system in the 12 patients and differentiated between lung and chest wall in ten of them. We determined the difference between end-expiratory lung volume on positive end-expiratory pressure (PEEP) and relaxation volume of the respiratory system on zero PEEP (ΔFRC). The recruited alveolar volume was computed as the ΔFRC times the ratio of static elastance of the respiratory system to the lung. These measurements together with arterial blood gases determination were made in supine position (SP1), after 1 h of PP and after 1 h of supine repositioning (SP2) at the same level of PEEP. The PaO₂/FIO₂ ratio improved from SP1 to PP (136 ± 17 vs 204 ± 24 mm Hg; p < 0.01). An PP-induced alveolar recruitment was found in five patients. The change in oxygenation correlated to the recruited volume. The static elastance of the chest wall decreased from 4.62 ± 0.99 cmH₂O/l in SP1 to 6.26 ± 0.54 cmH₂O/l in PP (p < 0.05) without any correlation to the change in oxygenation.¶Conclusions: Alveolar recruitment may be a mechanism of oxygenation improvement in some patients with acute hypoxemic respiratory failure. No correlation was found between change in oxygenation and chest wall elastic properties.     

Association between inhaled nitric oxide treatment and long-term pulmonary function in survivors of acute respiratory distress syndrome

ABSTRACT: INTRODUCTION: Assessment of treatments for acute respiratory distress syndrome (ARDS) has focused on short-term outcomes (for example, mortality); little information exists regarding long-term effects of ARDS treatment. Survivors of ARDS episodes may have long-term obstructive/restrictive pulmonary abnormalities and pulmonary gas exchange impairment. A 2004 prospective randomized placebo-controlled trial assessed the efficacy and safety of inhaled nitric oxide (iNO) in patients with non-septic ARDS; the primary endpoint was days alive and off assisted breathing. This analysis examined potential effects of iNO or placebo on pulmonary function six months post-treatment in ARDS survivors from that original study. METHODS: ARDS survivors (N = 92) from a large-scale randomized, placebo-controlled study evaluating mortality after either 5 ppm iNO or placebo for up to 28 days were assessed six months post-treatment. Pulmonary function testing across seven parameters was conducted. RESULTS: At 6 months post-treatment, results indicated significantly better absolute values for iNO versus placebo for mean ± SD total lung capacity (TLC, 5.54 ± 1.42 vs. 4.81 ± 1.00; P = 0.026). There were also significantly better values for mean ± SD percent predicted values for a) forced expiratory volume in 1 second (FEV1, 80.23 ± 21.21 vs. 69.51 ± 28.97; P = 0.042), b) forced vital capacity (FVC, 83.78 ± 19.37 vs. 69.84 ± 27.40; P = 0.019), c) FEV1/FVC (96.14 ± 13.79 vs. 87.92 ± 19.77; P = 0.033), and d) TLC (93.33 ± 18.21 vs. 76.10 ± 21.84; P < 0.001). Nonsignificant differences were found in absolute FEV1, FEV1/FVC, FVC, forced expiratory flow from 25% to 75% of FVC, functional residual capacity, and CO diffusion. CONCLUSIONS: ARDS patients surviving after treatment with low-dose iNO had significantly better values for select pulmonary function tests at six months post-treatment than placebo-treated patients. Further trials are warranted to determine the effects of iNO on chronic lung function in ARDS survivors, a factor in long-term morbidity and quality of life in this population. TRIAL REGISTRATION: A Double-blind, Randomized, Placebo-controlled, Dose-response Study of Inhaled Nitric Oxide in the Treatment of Acute Respiratory Distress Syndrome. NCT number: ISRCTN53268296.     

Regional distribution of gas and tissue in acute respiratory distress syndrome. III. Consequences for the effects of positive end-expiratory pressure

Objective: To determine whether differences in lung morphology assessed by computed tomography (CT) affect the response to positive end-expiratory pressure (PEEP).¶Design: Prospective study over a 53-month period.¶Setting: Fourteen-bed surgical intensive care unit of a university hospital.¶Patients and participants: Seventy-one consecutive patients with early adult respiratory distress syndrome (ARDS).¶Measurements and results: Fast spiral thoracic CT was performed at zero end-expiratory pressure (ZEEP) and after implementation of PEEP 10 cmH₂O. Hemodynamic and respiratory parameters were measured in both conditions. PEEP-induced overdistension and alveolar recruitment were quantified by specifically designed software (Lungview). Overdistension occurred only in the upper lobes and was significantly correlated with the volume of lung, characterized by a CT attenuation ranging between –900 and –800 HU in ZEEP conditions. Cardiorespiratory effects of PEEP were similar in patients with primary and secondary ARDS. PEEP-induced alveolar recruitment of the lower lobes was significantly correlated with their lung volume (gas + tissue) at functional residual capacity. PEEP-induced alveolar recruitment was greater in the lower lobes with “inflammatory atelectasis” than in the lower lobes with “mechanical atelectasis.” Lung morphology as assessed by CT markedly influenced the effects of PEEP: in patients with diffuse CT attenuations PEEP induced a marked alveolar recruitment without overdistension, whereas in patients with lobar CT attenuations PEEP induced a mild alveolar recruitment associated with overdistension of previously aerated lung areas. These results can be explained by the uneven distribution of regional compliance characterizing patients with lobar CT attenuations (compliant upper lobes and stiff lower lobes) contrasting with a more even distribution of regional compliances observed in patients with diffuse CT attenuations.¶Conclusions: In patients with ARDS, the cardiorespiratory effects of PEEP are affected by lung morphology rather than by the cause of the lung injury (primary versus secondary ARDS). The regional distribution of the loss of aeration and the type of atelectasis –“mechanical” with a massive loss of lung volume, or “inflammatory” with a preservation of lung volume – characterizing the lower lobes are the main determinants of the cardiorespiratory effects of PEEP.     

Application of a computerised method to measure static pressure volume curve in acute respiratory distress syndrome

Objective: To assess the safety and the bedside feasibility of a new computerised method to record the static pressure-volume curves (Pst/V) of the respiratory system.¶Design: The Pst/V curves were recorded in 13 medical patients with the acute respiratory distress syndrome (ARDS). During the Pst/V curve tracing the following parameters were recorded: time required for the recording and the automatic analysis of the Pst/V curve and modifications in electrocardiograms, blood pressure, and arterial oxygen satmation (SaO₂).¶Setting: The study was performed in the intensive care unit of the University of Naples “Federico II”.¶Results: No statistically significant modifications in heart rate (HR, b min^–1), blood pressure (BP, mmHg), and SaO₂ were observed between conditions at baseline (HR 97.2 ± 17.7; BP 65.4 ± 9.3; SaO₂ 93.6 ± 2.0), during the recording (HR 99.8 ± 19.5; BP 66.2 ± 11.6; SaO₂ 93.7 ± 2.4), and 2 min after the procedure (HR 98.2 ± 17.8; BP 65.2 ± 11.7; SaO₂ 93.7 ± 1.9). The Pst/V curves were recorded in 8.38 ± 1.19 min and fully analysed in 2.69 ± 0.85 min. Mean value of static compliance was 41.1 ± 12.7 ml cmH₂O^–1. A lower inflection point was found in ten patients (mean value 9.2 ± 1.9 cmH₂O).¶Conclusions: In ARDS patients, the present new computerised method gave valuable data to ordinary intensivists and was shown to be safe, easy, and fast.     

Influence of respiratory and inflammatory parameters preceding intubation on survival of patients with COVID-19 ARDS– A single centre retrospective analysis

It remains unclear if intubation and ventilation earlier in the disease course confers a survival advantage in acute respiratory distress syndrome. Our objective was to determine whether patients with COVID-19 who died following mechanical ventilation were more advanced in their disease compared to survivors. Forty-seven patients admitted directly to our centre received ventilation, of who 26 (57%) patients died. The rate of fall in SpO₂:FiO₂ ratio (p = 0.478) and increasing respiratory rate (p = 0.948) prior to IMV were similar between survivors and non-survivors. Our data support a trial of continuous positive airway pressure prior to IMV in patients with moderate-to-severe COVID-19 ARDS.     

A prospective longitudinal multicentre study of health related quality of life in ICU survivors with COPD

Introduction

Mortality amongst COPD patients treated on the ICU is high. Health-related quality of life (HRQL) after intensive care is a relevant concern for COPD patients, their families and providers of health care. Still, there are few HRQL studies after intensive care of this patient group. Our hypothesis was that HRQL of COPD patients treated on the ICU declines rapidly with time.

Methods

Fifty-one COPD patients (COPD-ICU group) with an ICU stay longer than 24 hours received a questionnaire at 6, 12 and 24 months after discharge from ICU. HRQL was measured using two generic instruments: the EuroQoL instrument (EQ-5D and EQ-VAS) and the Short Form 36 Health Survey (SF-36). The results were compared to HRQL of two reference groups from the general population; an age- and sex-adjusted reference population (Non-COPD reference) and a reference group with COPD (COPD reference).

Results

HRQL of the COPD-ICU group at 6 months after discharge from ICU was lower compared to the COPD reference group: Median EQ-5D was 0.66 vs. 0.73, P = 0.08 and median EQ-VAS was 50 vs.55, P < 0.05. There were no significant differences in the SF-36 dimensions between the COPD-ICU and COPD-reference groups, although the difference in physical functioning (PF) approached statistical significance (P = 0.059). Patients in the COPD-ICU group who were lost to follow-up after 6 months had low HRQL scores at 6 months. Scores for patients who died were generally lower compared to patients who failed to respond to the questionnaire. The PF and social functioning (SF) scores in those who died were significantly lower compared to patients with a complete follow up. HRQL of patients in the COPD-ICU group that survived a complete 24 months follow up was low but stable with no statistically significant decline from 6 to 24 months after ICU discharge. Their HRQL at 24 months was not significantly different from HRQL in the COPD reference group.

Conclusions

HRQL in COPD survivors after intensive care was low but did not decline from 6 to 24 months after discharge from ICU. Furthermore, HRQL at 24 months was similar to patients with COPD who had not received ICU treatment.     

A universal definition of ARDS: the PaO2/FiO2 ratio under a standard ventilatory setting—a prospective, multicenter validation study

Purpose

The PaO₂/FiO₂ is an integral part of the assessment of patients with acute respiratory distress syndrome (ARDS). The American-European Consensus Conference definition does not mandate any standardization procedure. We hypothesized that the use of PaO₂/FiO₂ calculated under a standard ventilatory setting within 24 h of ARDS diagnosis allows a more clinically relevant ARDS classification.

Methods

We studied 452 ARDS patients enrolled prospectively in two independent, multicenter cohorts treated with protective mechanical ventilation. At the time of ARDS diagnosis, patients had a PaO₂/FiO₂ ≤ 200. In the derivation cohort (n = 170), we measured PaO₂/FiO₂ with two levels of positive end-expiratory pressure (PEEP) (≥5 and ≥10 cmH₂O) and two levels of FiO₂ (≥0.5 and 1.0) at ARDS onset and 24 h later. Dependent upon PaO₂ response, patients were reclassified into three groups: mild (PaO₂/FiO₂ > 200), moderate (PaO₂/FiO₂ 101–200), and severe (PaO₂/FiO₂ ≤ 100) ARDS. The primary outcome measure was ICU mortality. The standard ventilatory setting that reached the highest significance difference in mortality among these categories was tested in a separate cohort (n = 282).

Results

The only standard ventilatory setting that identified the three PaO₂/FiO₂ risk categories in the derivation cohort was PEEP ≥ 10 cmH₂O and FiO₂ ≥ 0.5 at 24 h after ARDS onset (p = 0.0001). Using this ventilatory setting, patients in the validation cohort were reclassified as having mild ARDS (n = 47, mortality 17 %), moderate ARDS (n = 149, mortality 40.9 %), and severe ARDS (n = 86, mortality 58.1 %) (p = 0.00001).

Conclusions

Our method for assessing PaO₂/FiO₂ greatly improved risk stratification of ARDS and could be used for enrolling appropriate ARDS patients into therapeutic clinical trials.     

Angiotensin II formation and endothelin clearance in ARDS patients in supine and prone positions

Objective: In patients with acute respiratory distress syndrome (ARDS), the prone position may enhance oxygenation by changing ventilation/perfusion ratio. In this study, we investigated whether the prone position affects the net balance between pulmonary endothelin (ET-1) and angiotensin II (Ang II) production and clearance, two metabolic functions of lung endothelial cells.¶Setting: Anaesthesiological intensive care unit of a university hospital.¶Patients: Ten ARDS patients (Murray score > 2.5) were studied in both the supine position (SP) and the prone position (PP).¶Measurements and design: Blood samples were taken simultaneously from the patient in SP for assessment of mixed venous and arterial ET-1 and Ang II concentrations, and plasma renin concentration (PRC). This was repeated after 60 min in SP, immediately after turning the patient into PP, and 60 min thereafter. Net arterial/mixed venous ET-1 clearances and net Ang II formations were calculated.¶Results: arterial oxygen tension increased from SP to PP by an average of 60 mmHg, about 20 %. Arterial ET-1 concentrations of ARDS patients were 1.57 ± 1.1 pg/ml (mean ± SD) and within the range of healthy persons. Net ET-1 clearances were negative in SP, indicating pulmonary release of ET-1, and did not change in PP. Arterial Ang II concentrations (73 ± 56 pg/ml) as well as PRC (126 ± 85 pg/ml) were markedly elevated. Net transpulmonary Ang II formation did not change.¶Conclusion: Acute changes of oxygenation in ARDS patients by positioning do not induce any short-term effects on pulmonary ET-1 net clearance or Ang II net formation.     

Impact of the driving pressure on mortality in obese and non-obese ARDS patients: a retrospective study of 362 cases

Purpose

The relation between driving pressure (plateau pressure-positive end-expiratory pressure) and mortality has never been studied in obese ARDS patients. The main objective of this study was to evaluate the relationship between 90-day mortality and driving pressure in an ARDS population ventilated in the intensive care unit (ICU) according to obesity status.

Methods

We conducted a retrospective single-center study of prospectively collected data of all ARDS patients admitted consecutively to a mixed medical-surgical adult ICU from January 2009 to May 2017. Plateau pressure, compliance of the respiratory system (Crs) and driving pressure of the respiratory system within 24 h of ARDS diagnosis were compared between survivors and non-survivors at day 90 and between obese (body mass index?≥?30 kg/m²) and non-obese patients. Cox proportional hazard modeling was used for mortality at day 90.

Results

Three hundred sixty-two ARDS patients were included, 262 (72%) non-obese and 100 (28%) obese patients. Mortality rate at day 90 was respectively 47% (95% CI, 40–53) in the non-obese and 46% (95% CI, 36–56) in the obese patients. Driving pressure at day 1 in the non-obese patients was significantly lower in survivors at day 90 (11.9?±?4.2 cmH₂O) than in non-survivors (15.2?±?5.2 cmH₂O, p?<?0.001). Contrarily, in obese patients, driving pressure at day 1 was not significantly different between survivors (13.7?±?4.5 cmH₂O) and non-survivors (13.2?±?5.1 cmH₂O, p?=?0.41) at day 90. After three multivariate Cox analyses, plateau pressure [HR?=?1.04 (95% CI 1.01–1.07) for each point of increase], Crs [HR?=?0.97 (95% CI 0.96–0.99) for each point of increase] and driving pressure [HR?=?1.07 (95% CI 1.04–1.10) for each point of increase], respectively, were independently associated with 90-day mortality in non-obese patients, but not in obese patients.

Conclusions

Contrary to non-obese ARDS patients, driving pressure was not associated with mortality in obese ARDS patients.

     

Contribution of comorbidities to functional impairment is higher in heart failure with preserved than with reduced ejection fraction

Background

Comorbidities negatively affect prognosis more strongly in heart failure with preserved (HFpEF) than with reduced (HFrEF) ejection fraction. Their comparative impact on physical impairment in HFpEF and HFrEF has not been evaluated so far.

Methods and results

The frequency of 12 comorbidities and their impact on NYHA class and SF-36 physical functioning score (SF-36 PF) were evaluated in 1,294 patients with HFpEF and 2,785 with HFrEF. HFpEF patients had lower NYHA class (2.0?±?0.6 vs. 2.4?±?0.6, p?<?0.001) and higher SF-36 PF score (54.4?±?28.3 vs. 54.4?±?27.7, p?<?0.001). All comorbidities were significantly (p?<?0.05) more frequent in HFrEF, except hypertension and obesity, which were more frequent in HFpEF (p?<?0.001). Adjusting for age and gender, COPD, anemia, hyperuricemia, atrial fibrillation, renal dysfunction, cerebrovascular disease and diabetes had a similar (p for interaction >?0.05) negative effect in both groups. Obesity, coronary artery disease and peripheral arterial occlusive disease exerted a significantly (p?<?0.05) more adverse effect in HFpEF, while hypertension and hyperlipidemia were associated with fewer (p?<?0.05) symptoms in HFrEF only. The total impact of comorbidities on NYHA (AUC for prediction of NYHA III/IV vs. I/II) and SF-36 PF (r ²) in multivariate analyses was approximately 1.5-fold higher in HFpEF, and also much stronger than the impact of a 10% decrease in ejection fraction in HFrEF or a 5?mm decrease in left ventricular end-diastolic diameter in HFpEF.

Conclusion

The impact of comorbidities on physical impairment is higher in HFpEF than in HFrEF. This should be considered in the differential diagnosis and in the treatment of patients with HFpEF.     

Comparison of a specialist retrieval team with current United Kingdom practice for the transport of critically ill patients

Objective: The inter-hospital transfer of critically ill patients in the United Kingdom is commonly undertaken using standard ambulance under junior doctor escort, despite recommendations for the use of specialist retrieval teams. Patients are transferred into University College London Hospitals (UCLH) intensive care unit (ICU) by both methods. We undertook to evaluate the effect of transfer method on acute physiology (within 2 h of ICU admission) and early mortality ( < 12 h after ICU admission).¶Design: Retrospective review of all transfers over 1 year.¶Setting: UCLH ICU.¶Subjects: 259 transfers; 168 by specialist retrieval team (group A) and 91 by standard ambulance with doctor provided by referring hospital (group B).¶Interventions: None¶Main outcome measures: Acute physiology (pH, PaO₂, PaCO₂, heart rate (HR), mean arterial blood pressure (MAP), 24 h severity of illness scores (APACHE II, SAPS II), length of stay and mortality.¶Results: There were no differences in demographic characteristics or severity of illness between the two groups; nevertheless significantly more patients in group B than in group A were severely acidotic (pH < 7.1: 11 % vs. 3 %, p < 0.008) and hypotensive (MAP < 60: 18 % vs. 9 %, p < 0.03) upon arrival. In addition, there were more deaths within the first 12 h after admission with 7.7 % deaths (7/91) in group B transfers vs. 3 % (5/168) in group A.¶Conclusions: The use of a specialist transfer team may significantly improve the acute physiology of critically ill patients and may reduce early mortality in ICU.     

COVID-19 and non-COVID ARDS patients demonstrate a distinct response to low dose steroids- A retrospective observational study

Patients with COVID-19 ARDS have distinct physiological and immunological phenotypes compared to patients with non-COVID ARDS. Patients with COVID-19 ARDS (n = 32) had a significant improvement in PaO₂: FiO₂ ratio (p = 0.046) following low-dose steroid treatment, unlike patients with non-COVID ARDS (n = 16) (p = 0.529). Patients with COVID-19 ARDS had a greater fall in CRP compared to patients with non-COVID ARDS, albeit not statistically significant (p = 0.07). Our novel findings highlight differences in the underlying physiological and immunological phenotypes between COVID-19 and non-COVID ARDS, with implications for future ARDS studies.     

Physical declines occurring after hospital discharge in ARDS survivors: a 5-year longitudinal study

Purpose

Survivors of acute respiratory distress syndrome (ARDS) are at high risk for new or ongoing physical declines after hospital discharge. The objective of our study was to evaluate the epidemiology of physical declines over 5-year follow-up and identify patients at risk for decline.

Methods

This multi-site prospective cohort study evaluated ARDS survivors who completed a physical status assessment at 3 or 6 months post-discharge. Three measures were evaluated: muscle strength (Medical Resource Council sumscore); exercise capacity [6-min walk test (6MWT)]; physical functioning [36-Item Short Form Health Survey (SF-36 survey)]. Patients were defined as “declined” if a comparison of their current and prior score showed a decrease that was greater than the Reliable Change Index—or if the patient died. Risk factors [pre-ARDS baseline status, intensive care unit (ICU) illness severity, and other intensive care variables] were evaluated using longitudinal, generalized linear regression models for each measure.

Results

During the follow-up of 193 ARDS survivors (55 % male; median age 49 years), 166 (86 %) experienced decline in ≥1 physical measure (including death) and 133 (69 %) experienced a physical decline (excluding death). For all measures, age was a significant risk factor [odds ratios (OR) 1.34–1.69 per decade; p < 0.001]. Pre-ARDS comorbidity (Charlson Index) was independently associated with declines in strength and exercise capacity (OR 1.10 and 1.18, respectively; p < 0.02), and organ failure [maximum daily Sequential Organ Failure Assessment (SOFA) score in ICU] was associated with declines in strength (OR 1.06 per 1 point of SOFA score; p = 0.02).

Conclusions

Over the follow-up period, the majority of ARDS survivors experienced a physical decline, with older age and pre-ICU comorbidity being important risk factors for this decline.