Reverse triggering (RT) is a dyssynchrony defined by a respiratory muscle contraction following a passive mechanical insufflation. It is potentially harmful for the lung and the diaphragm, but its ...detection is challenging. Magnitude of effort generated by RT is currently unknown. Our objective was to validate supervised methods for automatic detection of RT using only airway pressure (Paw) and flow. A secondary objective was to describe the magnitude of the efforts generated during RT.
We developed algorithms for detection of RT using Paw and flow waveforms. Experts having Paw, flow and esophageal pressure (Pes) assessed automatic detection accuracy by comparison against visual assessment. Muscular pressure (Pmus) was measured from Pes during RT, triggered breaths and ineffective efforts.
Tracings from 20 hypoxemic patients were used (mean age 65 ± 12 years, 65% male, ICU survival 75%). RT was present in 24% of the breaths ranging from 0 (patients paralyzed or in pressure support ventilation) to 93.3%. Automatic detection accuracy was 95.5%: sensitivity 83.1%, specificity 99.4%, positive predictive value 97.6%, negative predictive value 95.0% and kappa index of 0.87. Pmus of RT ranged from 1.3 to 36.8 cmH
0, with a median of 8.7 cmH
0. RT with breath stacking had the highest levels of Pmus, and RTs with no breath stacking were of similar magnitude than pressure support breaths.
An automated detection tool using airway pressure and flow can diagnose reverse triggering with excellent accuracy. RT generates a median Pmus of 9 cmH
O with important variability between and within patients.
BEARDS, NCT03447288.
Tidal expiratory flow limitation (EFL
) complicates the delivery of mechanical ventilation but is only diagnosed by performing specific manoeuvres. Instantaneous analysis of expiratory resistance ...(Rex) can be an alternative way to detect EFL
without changing ventilatory settings. This study aimed to determine the agreement of EFL
detection by Rex analysis and the PEEP reduction manoeuvre using contingency table and agreement coefficient. The patterns of Rex were explored.
Medical patients ≥ 15-year-old receiving mechanical ventilation underwent a PEEP reduction manoeuvre from 5 cmH
O to zero for EFL
detection. Waveforms were recorded and analyzed off-line. The instantaneous Rex was calculated and was plotted against the volume axis, overlapped by the flow-volume loop for inspection. Lung mechanics, characteristics of the patients, and clinical outcomes were collected. The result of the Rex method was validated using a separate independent dataset.
339 patients initially enrolled and underwent a PEEP reduction. The prevalence of EFL
was 16.5%. EFL
patients had higher adjusted hospital mortality than non-EFL
cases. The Rex method showed 20% prevalence of EFL
and the result was 90.3% in agreement with PEEP reduction manoeuvre. In the validation dataset, the Rex method had resulted in 91.4% agreement. Three patterns of Rex were identified: no EFL
, early EFL
, associated with airway disease, and late EFL
, associated with non-airway diseases, including obesity. In early EFL
, external PEEP was less likely to eliminate EFL
.
The Rex method shows an excellent agreement with the PEEP reduction manoeuvre and allows real-time detection of EFL
. Two subtypes of EFL
are identified by Rex analysis.
Clinical trial registered with www.thaiclinicaltrials.org (TCTR20190318003). The registration date was on 18 March 2019, and the first subject enrollment was performed on 26 March 2019.
Background
Pain is a clinical feature of COVID‐19, however, data about persistent pain after hospital discharge, especially among ICU survivors is scarce. The aim of this study was to explore the ...incidence and characteristics of new‐onset pain and its impact on Health‐Related Quality of Life (HRQoL), and to quantify the presence of mood disorders in critically ill COVID‐19 survivors.
Methods
This is a preliminary report of PAIN‐COVID trial (NCT04394169) presenting a descriptive analysis in critically ill COVID‐19 survivors, following in person interview 1 month after hospital discharge. Pain was assessed using the Brief Pain Inventory, the Douleur Neuropathique 4 questionnaire and the Pain Catastrophizing Scale. HRQoL was evaluated with the EQ 5D/5L, and mood disorders with the Hospital Anxiety and Depression Scale (HADS).
Results
From 27 May to 19 July 2020, 203 patients were consecutively screened for eligibility, and 65 were included in this analysis. Of these, 50.8% patients reported new‐onset pain; 38.5% clinically significant pain (numerical rating score ≥3 for average pain intensity); 16.9% neuropathic pain; 4.6% pain catastrophizing thoughts, 44.6% pain in ≥2 body sites and 7.7% widespread pain. Patients with new‐onset pain had a worse EQ‐VAS and EQ index value (p < 0.001). Pain intensity was negatively correlated to both the former (Spearman ρ: −0.546, p < 0.001) and the latter (Spearman ρ: −0.387, p = 0.001). HADS anxiety and depression values equal or above eight were obtained in 10.8% and 7.7% of patients, respectively.
Conclusion
New‐onset pain in critically ill COVID‐19 survivors is frequent, and it is associated with a lower HRQoL.
Trial registration No.: NCT04394169. Registered 19 May 2020. https://clinicaltrials.gov/ct2/show/NCT04394169.
Significance
A substantial proportion of severe COVID‐19 survivors may develop clinically significant persistent pain, post‐intensive care syndrome and chronic ICU‐related pain. Given the number of infections worldwide and the unprecedented size of the population of critical illness survivors, providing information about the incidence of new‐onset pain, its characteristics, and its influence on the patients’ quality of life might help establish and improve pain management strategies.
...the very late group received more frequently tocilizumab as an adjunctive therapy: although the authors hypothesized that this was due to a longer time between steroid treatment and intubation, ...intubation is not a formal contraindication for such treatment. ...we think that the data presented in this brief report, although of great interest, might present important limitations as residual confounding could not be excluded. Effect of timing of intubation on clinical outcomes of critically ill patients with COVID-19: a systematic review and meta-analysis of non-randomized cohort studies.
Flow starvation is a type of patient-ventilator asynchrony that occurs when gas delivery does not fully meet the patients' ventilatory demand due to an insufficient airflow and/or a high inspiratory ...effort, and it is usually identified by visual inspection of airway pressure waveform. Clinical diagnosis is cumbersome and prone to underdiagnosis, being an opportunity for artificial intelligence. Our objective is to develop a supervised artificial intelligence algorithm for identifying airway pressure deformation during square-flow assisted ventilation and patient-triggered breaths.
Multicenter, observational study. Adult critically ill patients under mechanical ventilation > 24 h on square-flow assisted ventilation were included. As the reference, 5 intensive care experts classified airway pressure deformation severity. Convolutional neural network and recurrent neural network models were trained and evaluated using accuracy, precision, recall and F1 score. In a subgroup of patients with esophageal pressure measurement (ΔP
), we analyzed the association between the intensity of the inspiratory effort and the airway pressure deformation.
6428 breaths from 28 patients were analyzed, 42% were classified as having normal-mild, 23% moderate, and 34% severe airway pressure deformation. The accuracy of recurrent neural network algorithm and convolutional neural network were 87.9% 87.6-88.3, and 86.8% 86.6-87.4, respectively. Double triggering appeared in 8.8% of breaths, always in the presence of severe airway pressure deformation. The subgroup analysis demonstrated that 74.4% of breaths classified as severe airway pressure deformation had a ΔP
> 10 cmH
O and 37.2% a ΔP
> 15 cmH
O.
Recurrent neural network model appears excellent to identify airway pressure deformation due to flow starvation. It could be used as a real-time, 24-h bedside monitoring tool to minimize unrecognized periods of inappropriate patient-ventilator interaction.
Despite the benefits of mechanical ventilation, its use in critically ill patients is associated with complications and had led to the growth of noninvasive techniques. We assessed the effect of ...early intubation (first 8 h after vasopressor start) in septic shock patients, as compared to non-early intubated subjects (unexposed), regarding in-hospital mortality, intensive care and hospital length of stay.
This study involves secondary analysis of a multicenter prospective study. To adjust for baseline differences in potential confounders, propensity score matching was carried out. In-hospital mortality was analyzed in a time-to-event fashion, while length of stay was assessed as a median difference using bootstrapping.
A total of 735 patients (137 intubated in the first 8 h) were evaluated. Propensity score matching identified 78 pairs with similar severity and characteristics on admission. Intubation was used in all patients in the early intubation group and in 27 (35%) subjects beyond 8 h in the unexposed group. Mortality occurred in 35 (45%) and in 26 (33%) subjects in the early intubation and unexposed groups (hazard ratio 1.44 95% CI 0.86-2.39, p = 0.16). ICU and hospital length of stay were not different among groups 9 vs. 5 (95% CI 1 to 7) and 14 vs. 16 (95% CI - 7 to 8) days. All sensitivity analyses confirmed the robustness of our findings.
An early approach to invasive mechanical ventilation did not improve outcomes in this matched cohort of patients. The limited number of patients included in these analyses out the total number included in the study may limit generalizability of these findings. Trial registration NCT02780466. Registered on May 19, 2016.
Animal models of acute respiratory distress syndrome (ARDS) do not completely resemble human ARDS, struggling translational research. We aimed to characterize a porcine model of ARDS induced by ...pneumonia-the most common risk factor in humans-and analyze the additional effect of ventilator-induced lung injury (VILI).
Bronchoscopy-guided instillation of a multidrug-resistant Pseudomonas aeruginosa strain was performed in ten healthy pigs. In six animals (pneumonia-with-VILI group), pulmonary damage was further increased by VILI applied 3 h before instillation and until ARDS was diagnosed by PaO
/FiO
< 150 mmHg. Four animals (pneumonia-without-VILI group) were protectively ventilated 3 h before inoculum and thereafter. Gas exchange, respiratory mechanics, hemodynamics, microbiological studies and inflammatory markers were analyzed during the 96-h experiment. During necropsy, lobar samples were also analyzed.
All animals from pneumonia-with-VILI group reached Berlin criteria for ARDS diagnosis until the end of experiment. The mean duration under ARDS diagnosis was 46.8 ± 7.7 h; the lowest PaO
/FiO
was 83 ± 5.45 mmHg. The group of pigs that were not subjected to VILI did not meet ARDS criteria, even when presenting with bilateral pneumonia. Animals developing ARDS presented hemodynamic instability as well as severe hypercapnia despite high-minute ventilation. Unlike the pneumonia-without-VILI group, the ARDS animals presented lower static compliance (p = 0.011) and increased pulmonary permeability (p = 0.013). The highest burden of P. aeruginosa was found at pneumonia diagnosis in all animals, as well as a high inflammatory response shown by a release of interleukin (IL)-6 and IL-8. At histological examination, only animals comprising the pneumonia-with-VILI group presented signs consistent with diffuse alveolar damage.
In conclusion, we established an accurate pulmonary sepsis-induced ARDS model.
Abstract
Background
Critically ill patients with COVID-19 are an especially susceptible population to develop post-intensive care syndrome (PICS) due to acute respiratory distress syndrome (ARDS). ...Patients can suffer acute severe pain and may have long-term mental, cognitive, and functional health deterioration after discharge. However, few controlled trials are evaluating interventions for the prevention and treatment of PICS. The study hypothesis is that a specific care program based on early therapeutic education and psychological intervention improves the quality of life of patients at risk of developing PICS and chronic pain after COVID-19. The primary objective is to determine whether the program is superior to standard-of-care on health-related quality of life at 6 months after hospital discharge. The secondary objectives are to determine whether the intervention is superior to standard-of-care on health-related quality of life, incidence of chronic pain and degree of functional limitation, incidence of anxiety, depression, and post-traumatic stress syndrome at 3 and 6 months after hospital discharge.
Methods
The PAINCOVID trial is a unicentric randomized, controlled, patient-blinded superiority trial with two parallel groups. The primary endpoint is the health-related quality of life at 6 months after hospital discharge, and randomization will be performed with a 1:1 allocation ratio. This paper details the methodology and statistical analysis plan of the trial and was submitted before outcome data were available.
The estimated sample size is 84 patients, 42 for each arm. Assuming a lost to follow-up rate of 20%, a sample size of 102 patients is necessary (51 for each arm).
Discussion
This is the first randomized clinical trial assessing the effectiveness of an early care therapeutic education, and psychological intervention program for the management of PICS and chronic pain after COVID-19. The intervention will serve as proof of the need to implement early care programs at an early stage, having an incalculable impact given the current scenario of the pandemic.
Trial registration
This study is being conducted in accordance with the tenets of the Helsinki Declaration and has been approved by the authors’ institutional review board
Comité Ético de Investigación Clínica del Hospital Clínic de Barcelona
(approval number: HCB/2020/0549) and was registered on May 9, 2020, at clinicaltrials.gov (
NCT04394169
).
Purpose
Limb intensive care unit (ICU)-acquired weakness (ICUAW) and ICU acquired diaphragm weakness (DW) occur frequently in mechanically ventilated (MV) patients; their coexistence in cooperative ...and uncooperative patients is unknown. This study was designed to (1) describe the co-occurrence of the two conditions (2) evaluate the impact of ICUAW and DW on the ventilator-free days (VFDs) at 28 days and weaning success, and (3) assess the correlation between maximal inspiratory pressure (MIP) and thickening fraction (TFdi) in patients with DW.
Methods
This prospective pilot study was conducted in a single-center on 73 critically ill MV patients. Muscle weakness was defined as a Medical Research Council score < 48 in cooperative patients or a bilateral mean simplified peroneal nerve test < 5.26 mV in uncooperative patients. Diaphragm dysfunction was defined as MIP < 30 cm H
2
O or as a TFdi < 29%. Weaning success was defined according to weaning according to a new definition (WIND).
Results
Fifty-seven patients (78%) had ICUAW and 59 (81%) had DW. The coexistence of the two conditions occurred in 48 patients (65%), without association (χ
2
= 1.06,
p
= 0.304). In the adjusted analysis, ICUAW was independently related to VFDs at 28-days (estimate difference 6 days,
p
= 0.016), and WIND (OR of 3.62 for having WIND different than short weaning), whereas DW was not. The linear mixed model showed a significant but weak correlation between MIP and TFdi (
p
< 0.001).
Conclusion
This pilot study is the first to explore the coexistence of ICUAW and DW in both cooperative and uncooperative patients; a lack of association was found between DW and ICUAW when considering both cooperative and uncooperative patients. We found a strong correlation between ICUAW but not DW with the VFDs at 28 days and weaning success. A future larger study is warranted in order to confirm our results, and should also investigate the use of transdiaphragmatic twitch pressure measurement during bilateral anterior magnetic phrenic nerve stimulation for the diagnosis of DW.
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