Nicola Petrucci

Importance: In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited. Objective: To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy. Design, Setting, and Participants: Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020. Exposures: SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Main Outcomes and Measures: Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network. Results: Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received noninvasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and Fio2 was greater than 50% in 89% of patients. The median Pao2/Fio2 was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged ≤63 years) and older patients (n = 514 aged ≥64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0]; P = .94). Median Fio2 was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, -10% [95% CI, -14% to 6%]; P = .006), and median Pao2/Fio2 was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, -8 to 22]; P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68]; P < .001) and had lower Pao2/Fio2 (median [IQR], 146 [105-214] vs 173 [120-222]; median difference, -27 [95% CI, -42 to -12]; P = .005). Among the 1581 patients with ICU disposition data available as of March 25, 2020, 920 patients (58% [95% CI, 56%-61%]) were still in the ICU, 256 (16% [95% CI, 14%-18%]) were discharged from the ICU, and 405 (26% [95% CI, 23%-28%]) had died in the ICU. Older patients (n = 786; age ≥64 years) had higher mortality than younger patients (n = 795; age ≤63 years) (36% vs 15%; difference, 21% [95% CI, 17%-26%]; P < .001). Conclusions and Relevance: In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.

Background Patients with acute respiratory distress syndrome and acute lung injury require mechanical ventilatory support. Acute respiratory distress syndrome and acute lung injury are further complicated by ventilator‐induced lung injury. Lung protective ventilation strategies may lead to improved survival. This systematic review is an update of a Cochrane review originally published in 2003 and updated in 2007. Objectives To assess the effects of ventilation with lower tidal volume on morbidity and mortality in patients aged 16 years or older affected by acute respiratory distress syndrome and acute lung injury. A secondary objective was to determine whether the comparison between low and conventional tidal volume was different if a plateau airway pressure of greater than 30 to 35 cm H20 was used. Search methods In our previous 2007 updated review, we searched databases from inception until 2006. In this third updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and the Web of Science from 2006 to September 2012. We also updated our search of databases of ongoing research and of reference lists from 2006 to September 2012. Selection criteria We included randomized controlled trials comparing ventilation using either a lower tidal volume (Vt) or low airway driving pressure (plateau pressure 30 cm H2O or less), resulting in a tidal volume of 7 ml/kg or less, versus ventilation that used Vt in the range of 10 to 15 ml/kg in adults (16 years old or older) with acute respiratory distress syndrome and acute lung injury. Data collection and analysis We independently assessed trial quality and extracted data. Wherever appropriate, results were pooled. We applied fixed‐effect and random‐effects models. Main results We did not find any new study which were eligible for inclusion in this update. The total number of studies remained unchanged, six trials involving 1297 patients. Five trials had a low risk of bias. One trial had an unclear risk of bias. Mortality at day 28 was significantly reduced by lung‐protective ventilation with a relative risk (RR) of 0.74 (95% confidence interval (CI) 0.61 to 0.88); hospital mortality was reduced with a RR of 0.80 (95% CI 0.69 to 0.92). Overall mortality was not significantly different if a plateau pressure less than or equal to 31 cm H2O in the control group was used (RR 1.13, 95% CI 0.88 to 1.45). There was insufficient evidence for morbidity and long‐term outcomes. Authors' conclusions Clinical heterogeneity, such as different lengths of follow up and higher plateau pressure in control arms in two trials, makes the interpretation of the combined results difficult. Mortality was significantly reduced at day 28 and at the end of the hospital stay. The effects on long‐term mortality are unknown, although the possibility of a clinically relevant benefit cannot be excluded. Ventilation with lower tidal volumes is becoming a routine strategy of treatment of acute respiratory distress syndrome and acute lung injury, stopping investigators from carrying out additional trials.

BACKGROUND: Patients with acute respiratory distress syndrome and acute lung injury require mechanical ventilatory support. Acute respiratory distress syndrome and acute lung injury are further complicated by ventilator-induced lung injury. Lung-protective ventilation strategies may lead to improved survival. OBJECTIVES: To assess the effects of ventilation with lower tidal volume on morbidity and mortality in patients aged 16 years or older affected by acute respiratory distress syndrome and acute lung injury. A secondary objective was to determine whether the comparison between low and conventional tidal volume was different if a plateau airway pressure of greater than 30 to 35 cm H20 was used. SEARCH STRATEGY: In our original review, we searched databases from inception until 2003. In this updated review, we searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library 2006, Issue 3). We updated our search of MEDLINE, EMBASE, CINAHL and the Web of Science from 2003 to 2006. We also updated our search of intensive care journals and conference proceedings; databases of ongoing research, reference lists and 'grey literature' from 2003 to 2006. SELECTION CRITERIA: We included randomized controlled trials comparing ventilation using either lower tidal volume (Vt) or low airway driving pressure (plateau pressure 30 cm H2O or less), resulting in tidal volume of 7 ml/kg or less versus ventilation that uses Vt in the range of 10 to 15 ml/kg, in adults (16 years old or older). DATA COLLECTION AND ANALYSIS: We independently assessed trial quality and extracted data. Wherever appropriate, results were pooled. We applied fixed- and random-effects models. MAIN RESULTS: We found one new study in this update for a total of six trials, involving 1297 patients, which were eligible for inclusion. Mortality at day 28 was significantly reduced by lung-protective ventilation: relative risk (RR) 0.74 (95% confidence interval (CI) 0.61 to 0.88); hospital mortality was reduced: RR 0.80 (95% CI 0.69 to 0.92); overall mortality was not significantly different if a plateau pressure less than or equal to 31 cm H2O in control group was used: RR 1.13 (95% CI 0.88 to 1.45). There was insufficient evidence about morbidity and long term outcomes. AUTHORS' CONCLUSIONS: Clinical heterogeneity, such as different lengths of follow up and higher plateau pressure in control arms in two trials, make the interpretation of the combined results difficult. Mortality is significantly reduced at day 28 and at the end of hospital stay. The effects on long-term mortality are unknown, although the possibility of a clinically relevant benefit cannot be excluded.

Abstract Rationale Treatment with noninvasive ventilation (NIV) in coronavirus disease (COVID-19) is frequent. Shortage of intensive care unit (ICU) beds led clinicians to deliver NIV also outside ICUs. Data about the use of NIV in COVID-19 is limited. Objectives To describe the prevalence and clinical characteristics of patients with COVID-19 treated with NIV outside the ICUs. To investigate the factors associated with NIV failure (need for intubation or death). Methods In this prospective, single-day observational study, we enrolled adult patients with COVID-19 who were treated with NIV outside the ICU from 31 hospitals in Lombardy, Italy. Results We collected data on demographic and clinical characteristics, ventilatory management, and patient outcomes. Of 8,753 patients with COVID-19 present in the hospitals on the study day, 909 (10%) were receiving NIV outside the ICU. A majority of patients (778/909; 85%) patients were treated with continuous positive airway pressure (CPAP), which was delivered by helmet in 617 (68%) patients. NIV failed in 300 patients (37.6%), whereas 498 (62.4%) patients were discharged alive without intubation. Overall mortality was 25%. NIV failure occurred in 152/284 (53%) patients with an arterial oxygen pressure (PaO2)/fraction of inspired oxygen (Fi O2) ratio &amp;lt;150 mm Hg. Higher C-reactive protein and lower PaO2/Fi O2 and platelet counts were independently associated with increased risk of NIV failure. Conclusions The use of NIV outside the ICUs was common in COVID-19, with a predominant use of helmet CPAP, with a rate of success &amp;gt;60% and close to 75% in full-treatment patients. C-reactive protein, PaO2/Fi O2, and platelet counts were independently associated with increased risk of NIV failure. Clinical trial registered with ClinicalTrials.gov (NCT04382235).

BACKGROUND: Patients with acute respiratory distress syndrome and acute lung injury require mechanical ventilatory support. Acute respiratory distress syndrome and acute lung injury are further complicated by ventilator-induced lung injury. Lung-protective ventilation strategies may lead to improved survival. OBJECTIVES: To assess the effects of ventilation with lower tidal volume on morbidity and mortality in patients aged 16 years or older affected by acute respiratory distress syndrome and acute lung injury. A secondary objective was to determine whether the comparison between low and conventional tidal volume was different if a plateau airway pressure of greater than 30 to 35 cm H20 was used. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library issue 4, 2003; MEDLINE (1966 to October 2003); EMBASE and CINAHL (1982 to October 2003); intensive care journals and conference proceedings; databases of ongoing research, reference lists and 'grey literature'. SELECTION CRITERIA: Randomized trials comparing ventilation using either lower tidal volume or low airway driving pressure (plateau pressure 30 cm H(2)O or less), resulting in tidal volume of 7 ml/kg or less versus ventilation that uses Vt in the range of 10 to 15 ml/kg, in adults (aged 16 years or older). DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Wherever appropriate, results were pooled. Fixed and random effects models were applied. MAIN RESULTS: Five trials, involving 1202 patients, were eligible. Mortality at day 28 was significantly reduced by lung-protective ventilation: relative risk 0.74 (confidence interval 0.61 to 0.88), whereas beneficial effect on long-term mortality was uncertain: relative risk 0.84 (confidence interval 0.68 to 1.05). The comparison between low and conventional tidal volume was not significantly different if a plateau pressure less than or equal to 31 cm H2O in control group was used: relative risk 1.13 (confidence interval 0.88 to 1.45). There was insufficient evidence about morbidity and long term outcomes. REVIEWERS' CONCLUSIONS: Clinical heterogeneity, such as different lengths of follow up and higher plateau pressure in control arms in two trials make the interpretation of the combined results difficult. Mortality is significantly reduced at day 28 and the effects on long term mortality are uncertain, although the possibility of a clinically relevant benefit cannot be excluded.