The PANDORA Study: Prevalence and Outcome of Acute Hypoxemic Respiratory Failure in the Pre-COVID-19 Era

Abstract

OBJECTIVES: To establish the epidemiological characteristics, ventilator management, and outcomes in patients with acute hypoxemic respiratory failure (AHRF), with or without acute respiratory distress syndrome (ARDS), in the era of lung-protective mechanical ventilation (MV). DESIGN: A 6-month prospective, epidemiological, observational study. SETTING: A network of 22 multidisciplinary ICUs in Spain. PATIENTS: Consecutive mechanically ventilated patients with AHRF (defined as Pao2/Fio2 ≤ 300 mm Hg on positive end-expiratory pressure [PEEP] ≥ 5 cm H2O and Fio2 ≥ 0.3) and followed-up until hospital discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were prevalence of AHRF and ICU mortality. Secondary outcomes included prevalence of ARDS, ventilatory management, and use of adjunctive therapies. During the study period, 9,803 patients were admitted: 4,456 (45.5%) received MV, 1,271 (13%) met AHRF criteria (1,241 were included into the study: 333 [26.8%] met Berlin ARDS criteria and 908 [73.2%] did not). At baseline, tidal volume was 6.9 ± 1.1 mL/kg predicted body weight, PEEP 8.4 ± 3.1 cm H2O, Fio2 0.63 ± 0.22, and plateau pressure 21.5 ± 5.4 cm H2O. ARDS patients received higher Fio2 and PEEP than non-ARDS (0.75 ± 0.22 vs 0.59 ± 0.20 cm H2O and 10.3 ± 3.4 vs 7.7 ± 2.6 cm H2O, respectively [p < 0.0001]). Adjunctive therapies were rarely used in non-ARDS patients. Patients without ARDS had higher ventilator-free days than ARDS (12.2 ± 11.6 vs 9.3 ± 9.7 d; p < 0.001). All-cause ICU mortality was similar in AHRF with or without ARDS (34.8% [95% CI, 29.7–40.2] vs 35.5% [95% CI, 32.3–38.7]; p = 0.837). CONCLUSIONS: AHRF without ARDS is a very common syndrome in the ICU with a high mortality that requires specific studies into its epidemiology and ventilatory management. We found that the prevalence of ARDS was much lower than reported in recent observational studies.

Respiratory Subsets in Patients with Moderate to Severe Acute Respiratory Distress Syndrome for Early Prediction of Death

“…Data were pooled from three prospective observational multicenter cohorts ( n = 300 patients in the ALIEN cohort, n = 300 patients in the STANDARDS cohort, and n = 400 patients in the STANDARDS-2 cohort) [ 9 , 12 , 27 ], enrolling consecutive patients managed with lung-protective MV (see the details in the Supplementary File ) and who met the current criteria for moderate to severe ARDS [ 2 ], which included: (i) having an initiating clinical condition; (ii) symptoms developing within one week of a known clinical insult, or new or worsening respiratory symptoms; (iii) bilateral pulmonary infiltrates revealed by chest imaging (a chest radiograph or a computed tomography scan); (iv) the absence of left atrial hypertension or no clinical signs of left heart failure; and (v) hypoxemia, as defined by PaO 2 /FiO 2 ≤ 200 mm Hg at PEEP ≥ 5 cm H 2 O regardless of the FiO 2 . Second, we confirmed the validity of the classification model in an independent cohort of 303 patients with moderate to severe ARDS managed with lung-protective MV who were included in a recent prospective observational multicenter study [ 28 ]. Each dataset had an adequate number of events (ICU deaths), as recommended [ 30 ].…”

“…This was an ancillary study using unrestricted data from our previously conducted and published studies [ 9 , 12 , 27 , 28 ] approved by the Ethics Committees of Hospital Universitario Dr. Negrín (Las Palmas de Gran Canaria, Spain), Hospital Virgen de la Luz (Cuenca, Spain), Hospital Clínico Universitario (Valladolid, Spain), and Hospital Universitario La Paz (Madrid, Spain), which have been adopted by all the participating centers, as required by Spanish legislation (see Supplementary File ). The study was considered an audit, with waived informed consent (see the Supplementary File ).…”

“…We performed an ancillary analysis of the data derived from 1303 patients with moderate to severe ARDS treated with lung-protective MV included in our previously conducted and published studies [ 9 , 12 , 27 , 28 ]. The study was conducted in two steps (see the Supplementary File ).…”

Clinical relevance of timing of assessment of ICU mortality in patients with moderate-to-severe Acute Respiratory Distress Syndrome

“…Acute respiratory distress syndrome (ARDS) is a form of acute hypoxemic respiratory failure secondary to a number of predisposing insults, including sepsis, pneumonia, and traumatic injury. More than a third of mechanically ventilated patients with ARDS die in the intensive care unit (ICU) 1 . Prevention of ICU death through therapeutic interventions is a major focus of clinical research in ARDS.…”

“…Among other considerations, participation in RCTs requires consent, and therefore, these trials do not include consecutive eligible patients. Moreover, most RCT patients are recruited from tertiary centers in high-income countries 1 , 6 .…”