key: cord-0887620-hpww1l6f
authors: van der Zee, Philip; Somhorst, Peter; Endeman, Henrik; Gommers, Diederik
title: Electrical Impedance Tomography for Positive End-Expiratory Pressure Titration in COVID-19–related Acute Respiratory Distress Syndrome
date: 2020-07-15
journal: Am J Respir Crit Care Med
DOI: 10.1164/rccm.202003-0816le
sha: 7c7559fdaa27b5d4aca7e993079a182803ae1fd2
doc_id: 887620
cord_uid: hpww1l6f

nan

Coronavirus disease (COVID-19) spreads rapidly and has already resulted in severe burden to hospitals and ICUs worldwide. Early reports described progression to acute respiratory distress syndrome (ARDS) in 29% of cases (1) .

It is unknown how to titrate positive end-expiratory pressure (PEEP) in patients with ARDS. Patient survival improved if higher PEEP successfully recruited atelectatic lung tissue (2) . However, excessive PEEP caused alveolar overdistention, resulting in reduced patient survival (3). Therefore, PEEP should be personalized to maximize alveolar recruitment and minimize the amount of alveolar overdistention. Electrical impedance tomography (EIT) provides a reliable bedside approach to detect both alveolar overdistention and alveolar collapse (4) .

We describe a case series of patients with COVID-19 and moderate to severe ARDS in whom EIT was applied to personalize PEEP based on the lowest relative alveolar overdistention and collapse. Subsequently, we compared this PEEP level with the PEEP that could have been set according to the lower or higher PEEP-FI O 2 table from the ALVEOLI trial (5) . These early experiences may help clinicians to titrate PEEP in patients with COVID-19 and ARDS.

Study design and inclusion criteria. We conducted this case series between March 1, 2020, and March 31, 2020, in our tertiary referral ICU (Erasmus Medical Center, Rotterdam, the Netherlands). All consecutive mechanically ventilated patients admitted to the ICU with COVID-19 and moderate to severe ARDS (according to the Berlin definition of ARDS) were included in this study. COVID-19 was defined as a positive result on a PCR of sputum, nasal swab, or pharyngeal swab specimen. The local medical ethical committee approved this study. Informed consent was obtained from all patients' legal representatives.

Study protocol. A PEEP trial was performed daily in all patients according to our local mechanical ventilation protocol. Patients were fully sedated with continuous intravenous infusion of propofol, midazolam, and opiates. Persisting spontaneous breathing efforts were prevented with increased sedation or neuromuscular blockade. Arterial blood pressure was measured continuously. Noradrenalin was titrated to maintain a mean arterial blood pressure above 65 mm Hg at the start of the PEEP trial.

All patients were ventilated in pressure-control mode. FI O 2 was titrated to obtain a peripheral oxygen saturation between 92% and 95%. The other mechanical ventilation parameters (i.e., PEEP driving pressure, respiratory rate, and inspiratory/expiratory ratio) remained unchanged. Plateau airway pressure and total PEEP were measured during a zero-flow state with an inspiratory and expiratory hold procedure, respectively. Absolute transpulmonary pressures were measured with an esophageal balloon catheter (CooperSurgical or NutriVent). The position and balloon inflation status were tested with chest compression during an expiratory hold maneuver.

We monitored bedside ventilation distribution with EIT (Pulmovista 500; Dräger or Enlight 1800; Timpel). An EIT belt was placed around the patient's thorax in the transversal plane corresponding with the fourth to fifth intercostal parasternal space. The belt was placed daily (Pulmovista) or once in 3 days (Enlight), according to manufacturer's instructions. EIT data were visualized on screen during the entire study protocol without repositioning the EIT belt.

Subsequently, we performed a decremental PEEP trial. The PEEP was increased stepwise until the PEEP was 10 cm H 2 O above the baseline PEEP with a minimum PEEP of 24 cm H 2 O (PEEP high ), corresponding with the maximum PEEP advised by the PEEP-FI O 2 table. The PEEP trial was limited to a lower PEEP level in case of hypotension (mean arterial blood pressure ,60 mm Hg) or desaturation (peripheral oxygen saturation ,88%). PEEP high was maintained for at least 1 minute. From PEEP high , the PEEP was reduced in 2-cm H 2 O steps of 30 seconds until the EIT showed evident collapse. The PEEP was reduced an additional 2 cm H 2 O to confirm a further increase in collapse. The EIT devices provided percentages of relative alveolar overdistention and collapse at every PEEP step. Lastly, the total PEEP was set (PEEP set ) at the PEEP level above the intersection of the curves representing relative alveolar overdistention and collapse ( Figure 1 ) (6) .

Baseline characteristics and laboratory analyses were retrieved from the patient information system. Diffuse or focal ARDS was established with chest X-ray or lung computed tomography (CT) scan, similar to the LIVE (Lung Imaging for Ventilatory Setting in ARDS) study (7) .

Statistical analysis. Data were presented as medians and interquartile ranges (IQRs). Only PEEP set , as determined by the first PEEP trial, of each patient was used for analyses. The absolute distance in cm H 2 O between PEEP set and the closest PEEP level that could have been set based on the lower PEEP-FI O 2 table or the higher PEEP-FI O 2 table from the ALVEOLI trial was calculated (5). The Wilcoxon signed-rank test was used to test the difference between PEEP set and the absolute distance to either the PEEP-FI O 2 table and to test the difference in PEEP set between the first and last PEEP trial (up to Day 7). Correlations were assessed using Spearman's rank correlation coefficient (r).

Study population. We included 15 patients with COVID-19-related ARDS (Table 1) week after ICU admission. In addition, 14 (93%) patients had or progressed to diffuse ARDS on their chest X-ray or lung CT scan.

PEEP set in COVID-19-related ARDS. We conducted a total of 63 PEEP trials, of which 52 were performed in the supine position. The median amount of PEEP trials per patient was 3 (IQR, 2-4.5 (Figure 2A ). There was no correlation between PEEP set and FI O 2 (r = 0.11; P = 0.69). However, we did find a significant correlation between PEEP set and BMI (r = 0.76; P = 0.001) ( Figure 2B ). PEEP set did not change significantly over time ( Figure 2C ).

In 15 patients with COVID-19-related ARDS, personalized PEEP at the level of lowest relative alveolar overdistention and collapse, as measured with EIT, resulted in high PEEP. These PEEP levels did not result in high driving pressure or transpulmonary pressure. In addition, PEEP trials did not result in relevant hemodynamic instability or pneumothorax. PEEP set corresponded better with the higher PEEP-FI O 2 table than the lower PEEP-FI O 2 table and was positively correlated with BMI.

In COVID-19-related ARDS, both a low lung recruitability (L-type) and a high lung recruitability phenotype (H-type) have been described based on lung compliance and the amount of nonaerated lung tissue on lung CT scans (8) . Especially in patients with the Relative alveolar overdistention and collapse and the dynamic compliance of the respiratory system are shown during a decremental PEEP trial. At 29 cm H 2 O PEEP, there is relative alveolar overdistention but no relative collapse, whereas at 9 cm H 2 O PEEP, there is relative alveolar collapse but no relative overdistention. The total PEEP was set at the PEEP level above the intersection of the curves representing relative alveolar overdistention and collapse, in this case 21 cm H 2 O (6). Images: Pulmovista 500, Dräger. L-type, low PEEP was advised because higher PEEP would only result in alveolar overdistention without the benefit of alveolar recruitment. In 12 patients with COVID-19-related ARDS, Pan and colleagues (9) used the recruitment-to-inflation ratio and found that lung recruitability was low as well. However, in our first 15 patients with COVID-19-related ARDS, personalized PEEP at the level of lowest relative alveolar overdistention and collapse, as measured with EIT, resulted in high PEEP. Perhaps we included only patients with the H-type, but it is more likely that both phenotypes are the extremes of a recruitability continuum. The recruitability continuum represents the amount of nonaerated lung tissue resulting from edema. Gattinoni and colleagues (8) already described that one patient with COVID-19-related ARDS could progress from the L-type to the H-type as the amount of nonaerated lung tissue increased. If these results can be generalized, most patients with COVID-19 will become recruitable to some extent. The potential changes in recruitability over time make a personalized PEEP titration approach very interesting, although we did not observe a significant change in PEEP set over time.

In addition, a secondary analysis of the ALVEOLI trial found that higher PEEP improved survival in patients with a hyperinflammatory ARDS phenotype (10) . The hyperinflammatory phenotype could be predicted accurately using IL-6, tumor necrosis factor receptor, and vasopressors. Given the very high C-reactive protein concentrations and the use of vasopressors in all our patients, we assumed that the majority of patients in our study were in a hyperinflammatory state.

The LIVE trial predicted PEEP response based on lung morphology and found that patients with focal ARDS benefited from lower PEEP and that patients with diffuse ARDS benefited from higher PEEP (7) . In our study, the majority of patients had or progressed to diffuse ARDS, based on chest X-ray or lung CT scan. As a consequence, these patients with COVID-19 were likely to respond to higher PEEP.

We realize that the availability of EIT is limited in ICUs worldwide. In clinical practice, the PEEP-FI O 2 table is often used because it is a simple approach to titrate PEEP. This study showed that PEEP set at the level of lowest relative alveolar overdistention and collapse, as measured with EIT, corresponded better with the higher PEEP-FI O 2 table in 15 patients with COVID-19-related ARDS. However, the patients in our study had a high BMI, resulting in a lower transpulmonary pressure and increased PEEP requirement. Higher PEEP should be used with caution in patients with focal ARDS or low BMI. Moreover, response to higher PEEP should always be monitored in terms of driving pressure (2) or oxygenation (11) . n Author disclosures are available with the text of this letter at www.atsjournals.org. to be used according to the lower and higher PEEP-FI O 2 tables from the ALVEOLI trial. Each marker represents PEEP set at the level of lowest relative alveolar overdistention and collapse as measured with electrical impedance tomography. Only the first PEEP trial of each patient is presented. The crosses indicate subjects who died within 28 days following ICU admission. There was no correlation between PEEP set and FI O 2 (r = 0.11; P = 0.69). (B) PEEP set versus body mass index (BMI). The correlation between BMI and PEEP set after the first PEEP trial for each patient is shown. Spearman's rank correlation coefficient r = 0.76 with P = 0.001. Similar markers in Figures 2A and 2B represent the same patient. (C) Change in PEEP compared with the first PEEP trial. The change in PEEP set compared with the first PEEP trial is represented by the median (orange lines), interquartile ranges (boxes), and minimum and maximum values (whiskers). PEEP set did not change significantly over time. The number between parentheses represents the number of patients measured at that day.

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Driving pressure and survival in the acute respiratory distress syndrome

low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial

Chest electrical impedance tomography examination, data analysis, terminology, clinical use and recommendations: consensus statement of the TRanslational EIT developmeNt stuDy group

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Individual positive end-expiratory pressure settings optimize intraoperative mechanical ventilation and reduce postoperative atelectasis

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COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med

Lung recruitability in COVID-19-associated acute respiratory distress syndrome: a single-center observational study

Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials

Oxygenation response to positive end-expiratory pressure predicts mortality in acute respiratory distress syndrome: a secondary analysis of the LOVS and ExPress trials

Copyright © 2020 by the American Thoracic Society Bronchoscopy in Patients with COVID-19 with Invasive Mechanical Ventilation: A Single-Center Experience

The authors thank all ICU personnel who enabled us to perform this study. 

Severe coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to acute respiratory distress syndrome and hypoxemic respiratory failure (1) .The University Hospital de la Santa Creu i Sant Pau serves an area of downtown Barcelona, Spain, of about 420,000 citizens. The first case of COVID-19 at our hospital was detected on March 17, 2020. The first two cases in the ICU were detected on March 13, and the number of beds dedicated to intensive care multiplied by four, with 163 new ICU admissions and 139 patients requiring mechanical ventilation between March 13 and April 4. During this period, 59 patients were discharged, 23 died, and 81 were still in the ICU.BAL, bronchial wash, and protected specimen brush are bronchoscopic procedures used to provide microbiological samples from lower respiratory airways. However, because of the risk of viral transmission, bronchoscopy is not routinely indicated for the diagnosis of COVID-19 (2) .Bronchoscopy in critically ill patients with COVID-19 has been required to manage complications (atelectasis, hemoptysis, etc.) as well as to obtain samples for microbiological cultures and to assist in the management of artificial airways (guide intubation and percutaneous tracheostomy) (3).Because no series of intubated patients with COVID-19 submitted to bronchoscopy has been published so far, we describe our experience in performing flexible bronchoscopies in patients with COVID-19 with severe acute hypoxemic respiratory failure requiring invasive mechanical ventilation during the first 3 weeks of the epidemic outbreak.Between March 16 and April 4, 2020, a total of 101 bronchoscopies were performed in 93 patients with COVID-19. Eight patients required two bronchoscopies.Indications for bronchoscopy were as follows: radiological and/or clinical deterioration suggesting possible superinfection (63/101) as well as airway secretion management with/without atelectasis (38/101). Intensivists indicated procedures 6.6 days (range, 1-17) after intubation. At the time of indication, the median FI O 2 was 0.8 (interquartile range [IQR], 0.67-0.82), the median positive end-expiratory pressure was 10 cm H 2 O (IQR, [9] [10] [11] , and the median Pa O 2 /FI O 2 ratio was 111 (IQR, 103-125).Procedures were performed in either supine (74/101) or prone (27/101) position, under usual intravenous sedation and with pressure-controlled ventilation mode. Disposable scopes were used in all cases (Ambu aScope 4 Broncho, Large 5.8/2.8. Ambu A/S), and minimal staff attended the procedure bedside (one expert bronchoscopist occasionally accompanied by a staff intensivist). One out of two bronchoscopists got infected with SARS-CoV-2 and developed COVID-19. As a consequence, our colleague had to be replaced by another bronchoscopist during the third week.Before the procedure, all the necessary equipment and materials were prepared outside the patient room, including saline, syringes, mucoactive drugs, microbiological recipients, connections, and bronchoscopy system (scope and screen). A negative-pressure room was not always available for the procedures owing to the variety of locations adapted for intensive care support. As recommended (2) , level III of personal protective equipment was used, including N95 or FPP3 mask, goggles, double gloves, and a plastic protective gown including head and neck cover.Bronchoscopic examination included orotracheal tube positioning check, direct inspection of tracheal and bronchial mucosa, suctioning of secretions, and mucoactive agent instillation if necessary (hypertonic saline combined with hyaluronic acid), and in 63 cases, a mini-BAL with 60-ml saline aliquots at room temperature was performed just before the end of procedure for microbiological sampling. The bronchial segment to