Study objectives

We sought to characterise 90-day mortality, time spent on mechanical ventilation, ICU and hospital lengths of stay, mechanical ventilation strategies and selected aspects of clinical management of critically ill patients requiring at least 24 h of invasive mechanical ventilation in five ICUs in Lima, Peru, and in one ICU in the USA (figure 1). We further sought to characterise the proportion of patients admitted to the ICU with acute respiratory distress syndrome (ARDS); proportion of patients who developed ARDS while in the ICU; and vital status, physical and mental health at 6, 12, 24 and 60 months after hospitalisation in a subset of participants.

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Figure 1

Flowchart of participating intensive care units (ICU).

Outcomes

Primary outcomes for this study are 90-day mortality, time on mechanical ventilation, ICU and hospital lengths of stay, and prevalence of ARDS. Additional outcomes include vital status at 6, 12, 24 and 60 months for survivors of hospital discharge among participants in Peruvian ICUs. A subset of participants will be asked to undergo a follow-up evaluation at 6 months after the date of ICU admission to assess the long-term physical and emotional impact of their hospital stay.

Study design

The INTENSIVOS (‘critical’ in Spanish) cohort is a prospective, observational study. Enrolment began in December 2010 and ended in October 2013. Vital status follow-up and evaluation of physical and mental health in a subset of survivors will continue through October 2018. This manuscript was written concurrently with the implementation of the protocol and start of this study. At enrolment, we obtained demographic, chronic disease and acute physiological data for all patients meeting the eligibility criteria. They were followed daily to monitor vital status, clinical and ventilator management, acute physiology and use of sedation during their ICU stay for up to 28 days in the ICU, until ICU discharge or death. Patients successfully discharged from the ICU were followed for vital status during their inpatient hospital stay. All patients were contacted at 90 days after enrolment to assess their vital status. A subset of participants who survived until hospital discharge were asked to participate in an ancillary study and undergo a battery of tests to assess physical and mental health after hospitalisation. We aim to include 150 participants. Long-term outcomes will include vital status at 6, 12, 24 and 60 months, lung function, 6 min walk test, handgrip strength, respiratory symptoms, presence of anxiety or post-traumatic stress disorder (PTSD), and depression. The instruments used to evaluate these outcomes include the Hospital Anxiety and Depression Scale,11 the European Quality of Life 5 Dimensions 5 Levels Classification System,12 the Pittsburgh Sleep Quality Index,13 the Impact of Event Scale—Revised,14 the Telephone Interview for Cognitive Status,15 the 36-item short-form health survey,16 and the Katz and Lawton-Brody Activities of Daily Living Scale.

Eligibility criteria

Eligibility criteria were: (1) age >18 years, (2) at least 24 h of invasive mechanical ventilation in one of the ICUs participating in the study and (3) enrolment into the study within 48 h of onset of mechanical ventilation.

Study sites

The study was conducted in five ICUs at four public hospitals of the Social Security System (ESSALUD) and Ministry of Health (MINSA) in Lima, Peru, and in the Medical ICU (MICU) of Johns Hopkins Hospital (JHH; figure 2). We included only one ICU per hospital with the exception of Hospital Rebagliati, for which we included two ICUs. Participating ICUs were selected on the basis of high case volume and willingness to participate. A 4-week test period was initially carried out at each hospital in Peru to determine feasibility and monthly case volume. Of the six hospitals evaluated in Peru, two were unable to meet established a priori requirements during the test period and were not invited to continue in the study.

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Figure 2

Sequence of data submission (ICU, intensive care unit; PCF, Patient Contact Form; BCI, Baseline Clinical Form; DCI, Daily Clinical Form; CXR, chest X-ray form; SEF, Sepsis Evaluation Form; AFF, ARDS follow-up form; STF, Study Termination Form; 6MWT, 6 min walk test; PTSD, post-traumatic stress disorder).

Study team

Data collection and quality control was organised using a tiered approach. At each ICU, a team of 2–7 study nurses were responsible for paper-based data collection on a daily basis and an ICU physician (co-investigator) supervised the data collection and was responsible for data quality, review of clinical and ventilator data, and interpretation of the chest X-rays (CXR). In addition, a team of two study physician coordinators from the Clinical and Data Coordinating Center (DCC) oversaw the day-to-day operations of the study and acted as the liaison between the principal investigator and co-investigators. The DCC is composed of team members located in Peru and the USA. Study physician coordinators visited each ICU on an average of 2–3 times a week to verify data accuracy and fidelity along with co-investigators and study nurses, perform range checks and to obtain an electronic copy of CXRs. Incomplete or incorrectly entered case report forms (CRFs) were returned to study nurses for revision of missing or flagged data. Data forms were collected from all ICUs on a weekly basis and transferred to the DCC office in Peru for double data entry into a centralised database. The DCC data manager also conducted a careful review, and incomplete or incorrectly entered CRFs were returned to the study physician coordinators, who reviewed the missed or flagged data with the co-investigators and study nurses. Finally, a DCC nurse was responsible for follow-up telephone calls to assess 90-day vital status and to invite participants to join the long-term outcomes ancillary study among survivors.

Case report forms

CRFs were modelled on the forms used by ARDS Network trials with additional fields added to capture the Charlson comorbidity index,17 Acute Physiology And Chronic Health Evaluation (APACHE) II (A2F),18 APACHE III (A3F),19 Multiple Organ Dysfunction Score (MODS),20 Mortality Probability Admission Model III (MPM)21 and Sequential Organ Failure Assessment (SOFA) (SOF) scores.22 The CRFs were designed to capture demographic and chronic health information at baseline and daily information on acute physiology, selected aspects of clinical management, mechanical ventilation and weaning practices, and sedation management. Forms were originally written in English, translated into Spanish and then translated back into English to confirm accuracy of translation.

Prior to start of the study, the study team underwent an inperson training session on how to accurately record data in paper-based CRFs. Inperson training sessions were repeated approximately every 6 months during the first 2 years. All study team members were provided with a manual of operations with instructions on how to accurately fill the forms. These forms were completed in black or blue ink, reviewed by co-investigators and study physician coordinators and then transferred to the DCC where they were double-data entered into a centralised database. The CRFs were: a Patient Contact Form (PCF), Baseline Clinical Information Form (BCI), Daily Clinical Information Form (DCI) and a Study Termination Form (STF). Paper-based worksheets to calculate ICU severity scores such as A2F, A3F, MPM and SOF were also provided to the study team. Two additional forms were added later on and are available to a subset of study participants: ARDS follow-up form, in which study team members record additional ventilator parameters during the first 7 days after onset in patients who met criteria for ARDS; and Sepsis Evaluation Form, which recorded additional clinical parameters associated with sepsis during the first 14 days after enrolment.

The PCF included patient information such as name, date of birth, address and telephone contact information for determination of follow-up of vital status after hospital discharge. This is the only form that contained protected patient information linked to a corresponding unique participant identification code (PID) in the study. The PCFs were stored in locked cabinets and the electronic database was only available to the DCC data manager and to the nurse in charge of follow-up telephone calls. To complete the subsequent forms pertaining to a specific patient, the PID was transcribed exactly as it appeared on the PCF. PIDs were checked daily by ICU team members for verification of their accuracy. The PCFs for individual patients served as the only link between medical information and patient identifying information, and will be destroyed on completion of the study.

The BCI was completed on patient admission to the ICU. If a patient was readmitted to the ICU, a new BCI was filled. The BCI collected information in the first 24 h of mechanical ventilation The BCI also recorded height, chronic health information and acute physiology data. Height was measured using a standardised approach while in supine position. The BCI also had screening criteria for ARDS, modelled after that used by the ARDS Network, to assess whether or not a patient had ARDS on enrolment.

The DCI was collected daily, considering day 0 as the first 24 h of mechanical ventilation. It consisted of daily laboratory tests (complete blood count, comprehensive metabolic panel, arterial blood gas results), selected aspects of clinical management (fluid management, delirium management, prevention of ventilator-associated pneumonia, gastrointestinal ulcers and venous thromboembolism, lung protective ventilation, transfusion practices, use of central lines, arterial catheter and pulmonary artery catheters), mechanical ventilation management (mode of ventilation, tidal volume, airway pressures, oxygenation and positive end-expiratory pressure) and use of medications such as vasopressors, medications for prophylaxis for prevention of gastrointestinal ulcers and venous thromboembolism, opioids, benzodiazepines, sedatives, neuromuscular blockers, antipsychotics and antibiotics. DCIs were completed daily for the first 28 days or until patients died or were discharged from the ICU. Data for the DCI was captured over a defined 24 h period of time. To ensure that data was captured only once it was necessary to create an arbitrary 24 h period (ie, a study day). A study day was defined as the 24 h prior to 8:00 on the day of data collection. Participating hospitals were instructed to enter data for each DCI using values obtained as close as possible to 08:00.

The STF was used to record 90-day mortality and other ICU milestones, such as time on mechanical ventilation, dates of tracheostomy placement, and ICU and hospital discharge. In-hospital deaths were also recorded. Patients were followed throughout their hospital stay after ICU discharge to determine date of hospital discharge or death. Vital status was assessed on the STF at 15, 30, 45, 60 and 90 days after initiation of mechanical ventilation. After hospital discharge, vital status was obtained via a telephone call at 90 days and at subsequent dates as part of the long-term outcomes substudy.

Although participating ICUs in Peru are in the process of acquiring the necessary infrastructure for electronic medical records, none currently have it in place. Thus, data collectors manually recorded all data in paper-based forms. Although the CRFs have a section to record CXR findings, digital copies of all corresponding CXRs were also obtained and stored.

Sample size

Enrolment spanned a period of 3 years. We aimed to enrol at least 300 patients at each participating ICU for a total of 1800 participants across all six ICUs.

Characteristics of participating ICUs

The five Peruvian ICUs that took part in this study were from four public Peruvian hospitals of varying size and sources of funding; thus, there are some differences between the number of beds and influx of patients between units (table 1). Hospital Rebagliati, the site of two participating ICUs, is the largest centre with over 1500 beds and more than 55 000 yearly admissions. Hospital Nacional Almenara and Hospital Nacional Loayza are similar in size, both with approximately 800 beds and 2500 yearly admissions. Hospital Casimiro Ulloa is the smallest centre with only 76 beds; however, this is a Trauma and Emergency Medicine centre and thus, the number of emergency department visits and yearly admissions are much higher than would be expected for a hospital of this size. Reported annual ICU mortality for all ICUs was quite similar, ranging from 16.7% to 22.9%, and average annual ICU mortality is similar to that of the JHH MICU.

ICU organisation and structure

The five ICUs in Peru also have several structure-related (table 2) and process-related factors (table 3) in common. They are all closed ICUs with a 24 h, in-hospital attending intensivist coverage (vs the high-intensity, only daytime coverage model at JHH MICU), and with a variable number of critical care fellows and residents depending on the size of the teaching programme. The Peruvian ICUs average a ratio of 2 beds per nurse (ranging from 1.3:1 to 3:1) and there are physician assistants or nurse practitioners in the ICU as in the JHH MICU. A notable difference between the Peruvian ICUs and the JHH MICU is the absence of respiratory therapists in the former. Since there are no established ventilation protocols in use at the Peruvian ICUs, ventilator settings are based on intensivist preference. Delirium assessment is not commonly practiced by ICU nurses in Peru whereas this is the standard of care at the JHH MICU. Finally, the daily goals of care checklist is inconsistently used across participating ICUs in Peru.

Another difference between the Peruvian ICUs and JHH MICU is the presence of a multidisciplinary team during rounds (table 3). Medical rounds in the Peruvian ICUs were comprised only of physicians (attending intensivists, residents and fellows). Nurses do not do the round with the medical staff and instead, do their own rounds during shift change. Also, there are no pharmacists, physical therapists, social workers, nutritionists or palliative care specialists present during the rounds. The main communication between nursing and medical staff occurs once a day during a meeting between the attending physician and charge nurse. Finally, Peruvian ICUs do not have electronic patient records or computerised order entry systems as does the JHH MICU.