key: cord-0900002-l18kcc4y
authors: Pereira Rodriguez, J. E.; Quintero Gomez, J. C.; Lopez Florez, O.; Waiss Skvirsky, S. S.; Velasquez Badillo, X.
title: VENTILATORY SUPPORT IN SARS-VOC-2 DURING INTENSIVE THERAPY
date: 2020-05-19
journal: nan
DOI: 10.1101/2020.05.14.20098608
sha: af8117af297a68d4b19e205b20aae006d0606616
doc_id: 900002
cord_uid: l18kcc4y

Introduction: The SARS-CoV-2 disease outbreak has now become a pandemic. Critical patients with COVID-19 require basic and advanced respiratory support. Therefore, the objective was to describe the ventilatory support strategies in SARS-CoV-2 during intensive therapy. Materials and methods: A systematic review of observational studies of the available scientific literature was performed in accordance with the recommendations of the Cochrane collaboration and the criteria of the PRISMA Declaration. Results: Fifteen observational studies were included that gave a study population of 4,081 patients. Mechanical ventilation is the main respiratory support treatment for critically ill patients, which should be administered as soon as normal oxygenation cannot be maintained, and despite the fact that there is no current consensus on the parameters of mechanical ventilation, the evidence collected suggests the use of Fio2 on average 50%, PEEP of 14 cmH2O, lung compliance of 29-37 ml per cm of water, driving pressure between 12-14 cm of water and a plateau pressure of 22-25 cm of water. Conclusions: IL-6 is shown as a possible marker of respiratory failure and a worse prognosis as well as obesity. In addition, the use of prone position, neuromuscular blockade, pulmonary vasodilators, ECMO, and mechanical ventilation based on the clinical conditions and needs of the patient with COVID-19 are strategies that could benefit patients entering intensive therapy for SARS-CoV- 2.

Introducción: El brote de enfermedad por SARS-CoV-2 actualmente se ha convertido en una pandemia. Pacientes críticos con COVID-19 requieren soporte respiratorio básico y avanzado. Por lo tanto, el objetivo fue describir las estrategias de soporte ventilatorio en SARS-CoV-2 durante terapia intensiva. Materiales y métodos: Se realizó una revisión sistemática de estudios observacionales de la literatura científica disponible de acuerdo con las recomendaciones de la colaboración Cochrane y los criterios de la Declaración Understanding that there is still no clarity on the treatment for patients with Coronavirus, it has been described based on the pathophysiology of COVID-19 requiring advanced life support needs, ranging from oxygen supplementation through non-invasive ventilation, to invasive mechanical ventilation and vasopressor support; some secondary complications described in confirmed cases include cardiomyopathy, pulmonary embolism, and sudden death 3, 4 .

Based on the available data, it is defined that the viral infection is capable of producing an excessive immune reaction in the host, generating in turn what is called "cytokine storm", an effect of extensive tissue damage in cascade; Interleukin 6 (IL-6) is the main proinflammatory protein produced by leukocytes in cases of COVID-19, and which act on a large number of cells and tissues. In this way, and unlike other types of Coronavirus described above, SARS-CoV-2 has shown greater systemic involvement than others, mainly of respiratory origin associated with pneumonia 5,6 .

In one of the first reports on the disease, chest computed tomography (CT) was performed on patients with COVID-19, where pneumonia with abnormal findings was evident in all cases. About a third of them (13.32%) required intensive care unit (ICU) care, and there were 6 (15%) fatal cases. From this, the needs for assistance and support in the ICUs of all the countries of the world has increased. Likewise, each time the cases of acute respiratory distress syndrome (ARDS) and SARS-CoV-2-associated pneumonia continue to grow, which has forced the assistance of mechanical ventilation in these cases 7,8,9 . A report by the Intensive Care National Audit and Research Center (ICNARC) 10 in the United The percentage of patients with SARS-CoV-2 who require advanced ventilatory support, such as mechanical ventilation (MV), is high. However, there are currently no specific protocols for the management of MV in these patients. On the other hand, the need for updating based on scientific evidence on the assistance and management of mechanical ventilation in patients with SARS-CoV-2 has increased. Thus, this study aims to describe the ventilatory support strategies in SARS-CoV-2 during intensive therapy.

A systematic review was performed with a descriptive analysis of retrospective chronology of clinical trials, case reports, systematic reviews and meta-analyzes, available and published in indexed databases. Research that included experimental studies with human beings had informed consent under the ethical considerations of Helsinki 11 , for the regulation of experimental studies in living beings.

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The search for scientific documents was developed under the considerations and criteria of the PRISMA Flow Chart 12 (Transparent Reporting Items for Systematic Reviews and Meta-Analyzes) for the identification, screening, eligibility and inclusion of studies in systematic reviews. Different databases were reviewed for the identification of prospective documents based on the criteria of the PRISMA Diagram for text search. These search criteria are defined as: records identified through the database search, additional records identified through other sources, records after duplicates have been removed, selected records, full-text articles evaluated for eligibility, and finally studies included in qualitative synthesis. The databases identified for searching scientific studies included: PubMed and PubMed Central.

Descriptors associated with the variables described in the study title were used: mechanical ventilation & COVID-19; and the boolean operators: AND & OR. Thus, the search strategy was as follows: ("respiration, artificial" [MeSH Terms] OR ("respiration" AND "artificial") OR "artificial respiration" OR ("mechanical" AND "ventilation") OR "mechanical ventilation" [) AND ("COVID-19" OR "COVID-2019" OR "severe acute respiratory syndrome coronavirus 2" OR "severe acute respiratory syndrome coronavirus 2" OR "2019-nCoV" OR "SARS-CoV-2" OR "2019nCoV "OR (((" Wuhan "AND (" coronavirus "[MeSH Terms] OR" coronavirus ")) AND (2019/12 OR 2020))).

The selection of articles was made by the different authors of the study. At first, one author (JCQ-G) identified prospective studies, later a second author (OL-P) carried out the screening or screening process, a third researcher (SSW-S) applied eligibility criteria, and finally full text analysis and included by previous collaborators. To reduce study selection and inclusion bias, each of the research collaborators independently reviewed the studies chosen to analyze the full text using the PRISMA Checklist 13 , to finally agree on the studies to include in the sample (n). On the other hand, a fourth researcher.

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Eligibility criteria were defined in the PRISMA Checklist, according to the design characteristics of the included studies and characteristics of the reported population. Among the general criteria applied to all the studies, the place of publication, year of publication, type of literature, language of publication, study design, methodology, nature and characteristics of the population were taken into account.

From the above, studies published in indexed databases, documents available to date, scientific article-type texts, experimental and descriptive design research on the application and management of mechanical ventilation in humans with coronavirus acquired in the current pandemic. Some data such as sex, age, anthropometric characteristics, ethnicity and comorbidities were not filtered; one author (JEPR) verified that the ethical recommendations were complied with in each of the included investigations; all the collaborators verified the application of inclusion criteria.

The data were extracted into a selection matrix for the identified, screened, chosen and finally included studies, designed by the authors through "Excel" spreadsheets. Data from the studies chosen in the systematic review were collected on information analysis sheets. The information on the studies included in the review was described using characterization tables on text sheets.

Subjects of both genders, from any region of the world with confirmed diagnosis for COVID-19, who received supplemental oxygen from invasive or non-invasive mechanical ventilation were included.

After the initial search, 1,128 titles were identified regarding the use of mechanical ventilation in patients with COVID-19. A total of 104 documents were selected that described cases of patients who required mechanical ventilation due to the severe hypoxemia generated by the coronavirus.

Subsequently, 64 studies were chosen for full-text review (study objective, interventions carried out, results obtained and conclusions).

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The copyright holder for this preprint this version posted May 19, 2020. . https://doi.org/10.1101/2020.05.14.20098608 doi: medRxiv preprint Finally, 15 observational studies were included 15-29 (figure 1) after the full text review, on mechanical ventilation in COVID-19 that were published between February 9, 2020 and April 15, 2020; 3 clinical cohort studies 20,26,27 and 12 retrospective clinical studies [15] [16] [17] [18] [19] [21] [22] [23] [24] [25] 28, 29 . In this way, the sample size (n) of each included study, the main diagnosis, the information collection methodology, the time, results and conclusions of each study included in the systematic review were determined (table 1).

Illustration of the PRISMA Flowchart for the Identification, selection, eligibility and inclusion of studies in systematic reviews.

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The copyright holder for this preprint this version posted May 19, 2020. . https://doi.org/10.1101/2020.05.14.20098608 doi: medRxiv preprint A correct oxygenation strategy to avoid non-invasive mechanical ventilation saves lives . Seven-day mortality in SARS-CoV-2 requiring intubation was less than 15%, and 80% of patients still required mechanical ventilation. After 15 days of ICU admission, half of the patients remained intubated, while a third died.

Bhatraju PK, et al. 16 24

Retrospective clinical study score. However, the elevation of interleukin-6 (IL-6) was strongly associated with the need for mechanical ventilation (p = 1.2.10-5). Furthermore, the maximum level of IL-6 (cut 80 pg / ml) for each patient during the disease The IL-6 is an effective marker that could predict respiratory failure early with high accuracy and help physicians to correctly assign patients at an early stage. were administered in 18.6% of cases and more in the severe group than in the non-severe patients (44.5% vs. 13.7%, p <0.001). In addition, extracorporeal membrane oxygenation was adopted in 5 severe cases, but none in non-severe cases (P Severe pneumonia was independently associated with admission to the intensive care unit, mechanical ventilation, or death in the multivariate competitive risk model. <0.001). During hospital admission, the most common complication was pneumonia (79.1%), followed by ARDS (3.37%) and shock (1.00%). Zheng Y, et al. 29 3. 4

Retrospective clinical study P acientes with COVID-19 admitted to ICU R is astrea rum data until 5 March 2020. The cases were divided into cohort patients received noninvasive ventilation (INV) and cases requiring invasive mechanical ventilation ( IMV ). The characteristics between the two groups were compared.

6 weeks The complication rate was higher in V MI cases . Lymphocytopenia and neutrophilia occurred in most cases in both groups on the day of admission, however, lymphocyte levels progressively decreased and more severe lymphopenia occurred in the IMV group . Greater amounts of plasma IL-6 and IL-10 were found in both groups on the day of admission, whose progressive decrease occurred in cases of NIV compared to cases of IMV , and the levels were higher in cases of IMV during hospitalization.

Lymphocytopenia, neutrophilia, and increased IL-6 and IL-10 occurred in patients infected with SARS-CoV-2 in the ICU, however, their dynamics were significantly different in cases of IMV and NIV during hospitalization. .

LGA: acute gastrointestinal injury ; SOFA: Sequential Organ Failure Assessment Score ; WBC: white blood cell counts ; CI: confidence interval; PEEP: positive pressure at the end of expiration ; FiO2: inspiratory fraction of oxygen; PaO2: partial pressure of oxygen; ICU: intensive care unit; V NI: non-invasive ventilation ; IMV: invasive mechanical ventilation ; IL-6: interleukin 6; MRS; acute respiratory syndrome; LMWH : low molecular weight heparin r; ECMO: extracorporeal membrane circulation; RT-PCR: reverse transcription polymerase chain reaction ; BMI: body mass index; CRRT : continuous renal replacement therapies .

Mechanical ventilation is the main respiratory support treatment for critically ill patients, which should be administered as soon as normal oxygenation cannot be maintained 25 . The use of mechanical ventilation in critically ill COVID-19 patients remains a strategy for improving ventilation and mitigating the impact on acute respiratory distress syndrome developed by many patients with coronavirus.

Currently, there is little evidence on the needs for MV in patients with coronavirus and the prognosis for improvement. Critically ill patients with COVID-19 often require a moderate duration of mechanical ventilation and vasopressor support 24 .

Invasive mechanical ventilation in the prone position 15, 16, 26 , non-invasive mechanical ventilation [15] [16] [17] 19, 21, 23, 24, [26] [27] [28] [29] , high flow nasal cannula oxygen therapy 15, 23, 26 and extracorporeal membrane oxygenation (ECMO) 15, 17, 20, 29 , are some strategies in critically ill patients with SARS-CoV-2 who develop respiratory failure; as well as the use of neuromuscular blockade, inhaled pulmonary vasodilators and vasopressors 16 .

On the other hand, a high percentage of patients with SARS-CoV-2 who enter the ICU require prolonged mechanical ventilation 15,16,17 and a higher percentage requires invasive mechanical ventilation [15] [16] [17] 19, 20, 23, 24, [25] [26] [27] [28] . Mortality in patients with invasive mechanical ventilation (~18% to 33,3%) seems to be greater compared to non-invasive mechanical ventilation (~5% a 10%) 15,17 and even behaves up to 26% 19 .

Although there is no current consensus on the parameters of mechanical ventilation in patients with COVID-19, most studies suggest the volume-controlled / assisted ventilatory mode, the use of elevated Fio2 from day 1 of mechanical ventilation, among 60% and 90% 16, 19 , although the mean in the different studies was Fio2 50% 19 , a pulmonary compliance to 29-37 ml for cm to water 16 , positive pressure at the end of expiration (PEEP) of 14 (IQR, 12-16) cm H2O, plateau pressure of less than 30ml H2o, a driving pressure (the difference between the plateau pressure to the PEEP) of 12-14 cm of water 16, 19 and a pressure plateau of 22-25 cm of water 1616,19 are the guidelines recommended by the evidence collected.

Patients with cardiac injury and COVID-19 require more mechanical ventilation support than those without cardiac injury 26 ; 46.3% non-invasive and 22% invasive mechanical ventilation 26 . On the other hand, higher values of body mass index (IMC> 35 kg / m2) are associated with higher invasive mechanical ventilation requirements 27 . Similarly, higher levels of systemic blood pressure are associated with higher demand for MV and higher mortality 19, 22, 27 .

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The copyright holder for this preprint this version posted May 19, 2020. . Furthermore, the elevation of interleukin-6 (IL-6) is strongly associated with the need for mechanical ventilation. Furthermore, the maximum level of IL-6 (cut 80 pg / ml) for each patient during the disease predicts respiratory failure with high precision. The risk of respiratory failure for patients with IL-6 levels ≥ 80 pg / ml is 22 times higher compared to patients whose levels of IL-6 are lower. Also, the incidence of acute gastrointestinal injury (LGA) in critically ill patients with COVID-19 undergoing prolonged MV is frequent (86.7%) 21 .

Lymphocytopenia and neutrophilia occur in most cases, however, lymphocyte levels progressively decrease and lymphopenia occurs, which is more severe in patients with IMV 29 . Likewise, the rate of patients undergoing continuous renal replacement therapy for multiple organ failure and kidney injury in patients with SARS-CoV-2 is high 17, 24, 26 . Furthermore, critical COVID-19 can cause fatal respiratory distress syndrome and multiple organ failure with a high mortality rate17 and very frequently pneumonia (79.1%), followed by ARDS (3.3%) and shock (1.0%) 28 .

The use of methylprednisolone applied in critically ill COVID-19 patients appears to improve blood oxygen, reduce the rate of use of IMV, and the mortality rate 18 . On the other hand, other statements 31 mention that mechanical ventilation is capable of producing and aggravating lung damage by the administration of supplemental oxygen in inadequate amounts, highlighting that the effects of hyperoxia in the lungs can lead to the formation of alveolar hyaline membrane, edema, hyperplasia, proliferation of type II pneumocytes, destruction of type I pneumocytes, interstitial fibrosis and pulmonary vascular remodeling, data that resemble those . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 19, 2020. . In this way, it is reported in a study 34 that the prone position has a great impact on cardiopulmonary physiology, being a useful and accessible maneuver for most intensive care units, and the findings are also mentioned in the present investigation. relevant of this technique on terms of survival in patients with relatively severe ARDS (PaO2 / FiO2 ≤ 150mmHg) highlighting that it is necessary to reevaluate the levels of PEEP once the maneuver has been performed, adjusting to the particularities of each clinical situation.

In another study 35 , they mention that the use of muscle relaxants in the hypoxemic patient seeks to improve patient-ventilator synchrony, resulting in conflict with the development of myopathy as well as reducing the benefits of spontaneous breathing, as it was also shown that muscle relaxants, in patients with ARDS criteria treated under deep sedation showed an improvement in thoracic compliance and a decrease in O2 consumption.

That said, the use of non-invasive mechanical ventilation is questioned due to the findings found for its use in patients with ARDS as described by Franca Therefore, its use is limited to the different respiratory situations of the patient in which its placement is valued by the respiratory conditions as well as its hemodynamic stability described in the present investigation.

Consequently, Cristancho, W. (2020) 37 mentions the use of extracorporeal membrane oxygenation (ECMO) as an alternative to respiratory care, stating that its early use did not significantly improve mortality in patients with severe ARDS, however when used as a modality of rescue could help . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted May 19, 2020. . improve survival in patients with acute respiratory syndrome. And what has been said in this research, added to the corroborative evidence that we find from our findings, is to highlight that the actions in intensive care are fundamental for the survival of patients whose consequences have already been mentioned, together with prolonged periods of immobilization and bed rest, among which are those mentioned by the Pan American Health Organization 38 : Impaired lung function; physical deconditioning and muscle weakness; cofusional symptoms and other cognitive deficiencies; dysphagia and difficulties to communicate; mental health disorders and need for psychosocial support. Therefore, the need for rehabilitation professionals who play an important role in ICUs by facilitating early discharge is considered, which is especially important in a context of scarcity of hospital beds. Likewise, to prevent and intervene in sequelae associated with severe COVID-19. For this reason, rehabilitation professionals should be assigned to ICUs, hospital wards, transition facilities and the community.

However, it should be noted that the limitations of this study refer to the limited scientific evidence on the use of mechanical ventilation in patients with SARS-CoV-2, however, different authors suggest, like this review, that the Invasive mechanical ventilation is associated with a worse prognosis and a higher percentage of mortality when not used correctly and with academic grounds.

Similarly, the importance of very good early advanced ventilatory support is highlighted, since it can avoid the use of IMV in patients with COVID-19 [39] [40] [41] [42] [43] .

All SARS-CoV-2 patients require respiratory support and a very high rate requires mechanical ventilation. IL-6 is shown as a possible marker of respiratory failure and a worse prognosis, like that of patients with obesity. In addition, the use of prone position, neuromuscular blockade, pulmonary vasodilators, ECMO, and mechanical ventilation based on the clinical conditions and needs of the patient with COVID-19 are strategies that could benefit patients entering intensive therapy for COVID-19. Likewise, it is highlighted that the use of methylprednisolone seems to reduce mortality and hospital stay.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted May 19, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted May 19, 2020. . https://doi.org/10.1101/2020.05.14.20098608 doi: medRxiv preprint

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