Effect of Altitude on the Evolution of Acute Respiratory Distress Syndrome
Condition: ARDS; Hypoxia, Altitude; Altitude Sickness/Epidemiology
MeSH terms: Altitude Sickness; Hypoxia
Study type: Observational [Patient Registry]

Summary: 
      The purpose of this piece of research is to assess the effect of altitude on the clinical
      evolution of ARDS. For this purpose, patients who live and receive care at sea level are
      compared with those who live and receive care at high altitudes. For reasons of convenience,
      a cut-point of 1500 meters above sea level was chosen. In addition to this, it will be sought
      to assess whether adjusting the cut-points for the severity categories of ARDS improves the
      ability to predict some adverse events, by comparison with unadjusted cut-points. The results
      of this research will probably be disruptive, and will provide the first information yet
      about the effect of altitude on ARDS; they will therefore be of great interest for the
      international scientific community and for the direct care of patients. A high bibliometric
      impact is to be expected.
    

Detailed description: 
      HYPOTHESIS

      Physiological adaptations generated by living at high altitude modify the clinical evolution
      of ARDS.

      OBJECTIVE

      To describe the main clinical and developmental characteristics of ARDS diagnosed at
      altitudes greater than 1500 meters above sea level.

      To compare the main clinical and developmental characteristics of ARDS diagnosed at altitudes
      greater than 1500 meters above sea level with those of cases diagnosed at altitudes below
      1500 meters above sea level.

      METHODOLOGY

      Main events:

      Incidence of ARDS

      Mortality of ARDS

      Duration of mechanical ventilation and length of ICU stay of patients with ARDS Sequelae
      found 1 year and 3 years after diagnosis of ARDS

      Secondary events

      Recognition of ARDS by clinician

      Modes of mechanical ventilation

      Use of adjuvant therapies

      Design: observational, prospective, cohort, multicenter, international study

      Recruitment period: July 18, 2.016 - August 18, 2.016

      General Procedure

      The general organization chart of the study implies the participation of 3 lead researchers,
      at least 1 researcher/coordinator per country, and main researchers of each service.

      For the selection of participating services, a general invitation will be sent to all South
      American ICUs located at altitudes greater than 1500 meters above sea level, as well as a
      representative group of ICUs located below 1500 meters above sea level.

      The 2 cohorts (altitude and sea level) will be generated afterwards; the size of each cohort
      will be determined by convenience.

      For the selection of each participating service, the exploratory form (appendix 1) will be
      sent beforehand, in order to gain knowledge of its characteristics and possibilities; if the
      center meets the criteria, it will be enrolled and the rest of the documents (research
      protocols, appendices 2 and 3) will be sent to it.

      Once the participating services are defined, coordination videoconferences will be held
      before initiation of the study; an e-mail address will be set up for general coordination.
      All questions will be answered in less than 24 hours.

      The data will be collected in an Excel spreadsheet that will be sent to the coordinator of
      each country, and he will distribute it to the main researcher of each participating center.
      The information will be afterwards submitted to the general coordinators via the reverse
      pathway. All information will be sent by e-mail; in order to maintain confidentiality, the
      spreadsheets will be encrypted. The opening codes will be known only by the researchers
      responsible for each service, for each country, and by the lead researchers of the study. The
      data will be included by the main researcher of each center, under supervision of the
      coordinator of each country.

      Day 1 will be the day of admission to ICU with an unadjusted Pa02/Fi02 less than 300,
      regardless of the day the patient was admitted to hospital or to ICU.

      The protocol implies the gathering of basic data (appendix 3), that will be further obtained
      when the patients meets the criterion of Pa02/Fi02 less than 300. Gathering of data ends 28
      days after day 1 (IT MAY NOT CORRESPOND TO DAY 28 AFTER ADMISSION TO ICU); afterwards, data
      such as date of extubation, of discharge from ICU and from hospital, and condition upon
      discharge from hospital will be gathered.

      Clinical and analytic data will be gathered on admission, and afterwards at the same hour of
      the morning, while the patient continues under invasive mechanical ventilation.

      Diagnosis of ARDS is made by two procedures: (A) automatic, which will consist of
      individually picking each variable pertaining to the definition, and afterwards, by way of a
      computer algorithm, defining whether the patient complies with the Berlin definition; (B)
      clinical, the attending physician will be asked daily, since the moment when PaO2/Fi02<300,
      what the reason for hypoxemia is. Both diagnoses will be independent and double-blinded. The
      ratio of concordance will be calculated afterwards.

      Operational definitions:

      ARDS: Berlin definition.

      Days free of mechanical ventilation are the number of days in which no invasive mechanical
      ventilation is required, from disconnection to day 28. If the patient dies, 0 days free of
      mechanical ventilation will be considered.

      Driving pressure s the plateau pressure minus PEEP.

      Incidence is the number of patients diagnosed with ARDS divided by the number of patients who
      required invasive mechanical ventilation over the study period.

      Number of patients with ARDS per bed of the service is the number of patients diagnosed with
      ARDS divided by the number of beds suitable for mechanical ventilation available over the
      study period.

      Long-term follow-up (1 and 3 years) will be carried out by the central coordination team via
      e-mail or, occasionally, by telephone.

      Finally, a single database will be generated, with which the final report will be done.

      All patients with incomplete data will be excluded from the analysis.

      Statistical analysis:

      In order to fulfill objective 1, a descriptive epidemiological analysis of the primary and
      secondary events gathered in patients diagnosed with ARDS according to the Berlin definition.

      In order to fulfill objective 2, a comparison is made between the proportion of primary and
      secondary events between the altitude cohort and the sea-level cohort. Categorical variables
      are presented as number of cases and percentage, continuous variables are presented as median
      and percentiles 25-75. Categorical variables are compared by the chi-2 continuous variables
      are compared by Mann-Whitney or Kruskal-Wallis non-parametric tests.

      In order to fulfill objective 3, ROC curves will be made for each event, taking into
      consideration the unadjusted and altitude-adjusted Berlin definition as dependent variable.

      The final data report will be done following the recommendations of the Strengthening the
      Reporting of Observational Studies in Epidemiology (STROBE) statement guidelines for
      observational cohort studies.

      The whole statistical analysis will be made with the free R program
      (http://www.R-project.org). All P values will be two-tail P values, considering a <0.05 level
      of signification.

      ACCESSIBILITY OF DATA

      The data will be accessible to any researcher upon written request to the Latin American
      Network of High-Altitude Intensive Care Medicine (RELAMI).

      The request must be written in Spanish and include:

      justification for using the data

      commitment to using the data for exclusively scientific purposes (explicitly stating that
      they will not be used for economic purposes)

      commitment to publishing the data in a pubmed indexed journal within a one-year period

      proof of experience and background in the field of clinical research adhesion to the code of
      ethics

      RELAMI will analyze the request and decide within a 60-day period from receipt of the
      request. If the response is positive, the data will be sent anonymized; if it is negative,
      the reasons will be explained.

      ECONOMIC ASPECTS

      This study does not have sponsors. No researcher will receive economic compensation or any
      other type of reward for participating.

      ETHICAL ASPECTS

      This study will be carried out in accordance with the ethical principles established by the
      International Conference on Harmonization, guidelines for Good Clinical Practice (GCP), which
      stem from the Helsinki Declaration and applicable regulation norms.

      This study is considered to be of insignificant low risk, since it is an observational,
      non-interventional study, and the data are gathered without identification. Each
      participating ICU will process the pertaining institutional approvals, including a
      renunciation of ethical revision.

      Recorded dispensation of each participant for gathering clinical data without identification
      will be sought as part of routine clinical care.

      DATA MANAGEMENT AND DISSEMINATION OF RESULTS

      The lead researchers and the Coordination Center will act as guardians of the data. Reports
      of progress and final reports will be presented opportunely in national and international
      conferences, giving priority to presentation during annual conferences in Latin America.

      The results of the study will be published in indexed scientific journals, preferably of the
      first decile.

      Only aggregated and disidentified data will be publicly presented.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        ARDS patients diagnosed at altitudes greater than 1500 meters above sea level and those of
        cases diagnosed at altitudes below 1500 meters above sea level