Successful Versus Failed Transition From Controlled Ventilation to Pressure Support Ventilation in COVID-19 Patients: A Retrospective Cohort Study.

OBJECTIVES: In patients with COVID-19 respiratory failure, controlled mechanical ventilation (CMV) is often necessary during the acute phases of the disease. Weaning from CMV to pressure support ventilation (PSV) is a key objective when the patient's respiratory functions improve. Limited evidence exists regarding the factors predicting a successful transition to PSV and its impact on patient outcomes. DESIGN: Retrospective observational cohort study. SETTING: Twenty-four Italian ICUs from February 2020 to May 2020. PATIENTS: Mechanically ventilated ICU patients with COVID-19-induced respiratory failure. INTERVENTION: The transition period from CMV to PSV was evaluated. We defined it as "failure of assisted breathing" if the patient returned to CMV within the first 72 hours. MEASUREMENTS AND MAIN RESULTS: Of 1260 ICU patients screened, 514 were included. Three hundred fifty-seven patients successfully made the transition to PSV, while 157 failed. Pao2/Fio2 ratio before the transition emerged as an independent predictor of a successful shift (odds ratio 1.00; 95% CI, 0.99-1.00; p = 0.003). Patients in the success group displayed a better trend in Pao2/Fio2, Paco2, plateau and peak pressure, and pH level. Subjects in the failure group exhibited higher ICU mortality (hazard ratio 2.08; 95% CI, 1.42-3.06; p < 0.001), an extended ICU length of stay (successful vs. failure 21 ± 14 vs. 27 ± 17 d; p < 0.001) and a longer duration of mechanical ventilation (19 ± 18 vs. 24 ± 17 d, p = 0.04). CONCLUSIONS: Our study emphasizes that the Pao2/Fio2 ratio was the sole independent factor associated with a failed transition from CMV to PSV. The unsuccessful transition was associated with worse outcomes.

Could CPAP Devices Be Used to Ventilate Cardiac Arrest Patients? A Bench Study.

OBJECTIVES: To investigate the potential efficacy of a commercial continuous positive airway pressure (CPAP) ventilator to provide effective respiratory support in a simulated scenario of out-of-hospital cardiac arrest (OHCA). METHODS: The study was conducted on a high-fidelity manikin (SimMan 3 GTM, Laerdal, NOR) connected to the ASL 5000TM Lung Simulator (IngMar Medical, USA). To simulate OHCA, we set no spontaneous respiratory acts and physiological respiratory system resistance (13 cmH2O/L.sec) and compliance (50 mL/cmH2O). The Respironics BiPAP A40 ventilatorI (Philips, NL) was used to provide ventilatory support while operating in CPAP mode. Tests were performed at different values of positive pressure of the CPAP ventilator (PCPAP: 5, 7.5, 10, 12.5 and 15 cmH2O) and the intrapulmonary volume (tidal volume, Vt) measured via the simulator software computer interface. A trained physician performed the tests. Our primary outcome was a VT of ≈500-600 mL with an intermittent maneuver simulating cardiopulmonary resuscitation (CPR)-like ventilatory support practice according to international guideline-based target (1-sec ventilation followed by 1-sec pause). RESULTS: In intermittent ventilatory support tests, PCPAP levels of 12.5, and 15 cmH2O resulted in a VT equal to 508 ± 13 mL, and 557 ± 44 mL respectively (p = 0.04), thus approaching the VT target. CONCLUSIONS: We provide preliminary evidence of the potential efficacy of CPAP ventilators designed for home use to provide effective respiratory support to a simulated respiratory arrest patient.

Identifying Trauma Patients in Need for Emergency Surgery in the Prehospital Setting: The Prehospital Prediction of In-Hospital Emergency Treatment (PROPHET) Study.

Prehospital field triage often fails to accurately identify the need for emergent surgical or non-surgical procedures, resulting in inefficient resource utilization and increased costs. This study aimed to analyze prehospital factors associated with the need for emergent procedures (such as surgery or interventional angiography) within 6 h of hospital admission. Additionally, our goal was to develop a prehospital triage tool capable of estimating the likelihood of requiring an emergent procedure following hospital admission. We conducted a retrospective observational study, analyzing both prehospital and in-hospital data obtained from the Lombardy Trauma Registry. We conducted a multivariable logistic regression analysis to identify independent predictors of emergency procedures within the first 6 h from admission. Subsequently, we developed and internally validated a triage score composed of factors associated with the probability of requiring an emergency procedure. The study included a total of 3985 patients, among whom 295 (7.4%) required an emergent procedure within 6 h. Age, penetrating injury, downfall, cardiac arrest, poor neurological status, endotracheal intubation, systolic pressure, diastolic pressure, shock index, respiratory rate and tachycardia were identified as predictors of requiring an emergency procedure. A triage score generated from these predictors showed a good predictive power (AUC of the ROC curve: 0.81) to identify patients requiring an emergent surgical or non-surgical procedure within 6 h from hospital admission. The proposed triage score might contribute to predicting the need for immediate resource availability in trauma patients.

Impact of SARS-CoV-2 Omicron and Delta variants in patients requiring intensive care unit (ICU) admission for COVID-19, Northern Italy, December 2021 to January 2022.

This multicenter observational study included 171 COVID-19 adult patients hospitalized in the ICUs of nine hospitals in Lombardy (Northern Italy) from December, 1st 2021, to February, 9th 2022. During the study period, the Delta/Omicron variant ratio of cases decreased with a delay of two weeks in ICU patients compared to that in the community; a higher proportion of COVID-19 unvaccinated patients was infected by Delta than by Omicron whereas a higher rate of COVID-19 boosted patients was Omicron-infected. A higher number of comorbidities and a higher comorbidity score in ICU critically COVID-19 inpatients was positively associated with the Omicron infection as well in vaccinated individuals. Although people infected by Omicron have a lower risk of severe disease than those infected by Delta variant, the outcome, including the risk of ICU admission and the need for mechanical ventilation due to infection by Omicron versus Delta, remains uncertain. The continuous monitoring of the circulating SARS-CoV-2 variants remains a milestone to counteract this pandemic.

Systematic reviews and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: mortality, morbidity, and organ failure.

BACKGROUND: Mortality, morbidity, and organ failure are important and common serious harms after surgery. However, there are many candidate measures to describe these outcome domains. Definitions of these measures are highly variable, and validity is often unclear. As part of the International Standardised Endpoints in Perioperative Medicine (StEP) initiative, this study aimed to derive a set of standardised and valid measures of mortality, morbidity, and organ failure for use in perioperative clinical trials. METHODS: Three domains of endpoints (mortality, morbidity, and organ failure) were explored through systematic literature review and a three-stage Delphi consensus process using methods consistently applied across the StEP initiative. Reliability, feasibility, and patient-centredness were assessed in round 3 of the consensus process. RESULTS: A high level of consensus was achieved for two mortality time points, 30-day and 1-yr mortality, and these two measures are recommended. No organ failure endpoints achieved threshold criteria for consensus recommendation. The Clavien-Dindo classification of complications achieved threshold criteria for consensus in round 2 of the Delphi process but did not achieve the threshold criteria in round 3 where it scored equivalently to the Post Operative Morbidity Survey. Clavien-Dindo therefore received conditional endorsement as the most widely used measure. No composite measures of organ failure achieved an acceptable level of consensus. CONCLUSIONS: Both 30-day and 1-yr mortality measures are recommended. No measure is recommended for organ failure. One measure (Clavien-Dindo) is conditionally endorsed for postoperative morbidity, but our findings suggest that no single endpoint offers a reliable and valid measure to describe perioperative morbidity that is not dependent on the quality of deli-vered care. Further refinement of current measures, or development of novel measures, of postoperative morbidity might improve consensus in this area.

Noninvasive Ventilation for Acute Respiratory Failure in Pediatric Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) on the use of noninvasive ventilation (NIV) for acute respiratory failure (ARF) in pediatric patients. DATA SOURCES: We searched PubMed, EMBASE, the Cochrane Central Register of Clinical Trials, and Clinicaltrials.gov with a last update on July 31, 2022. STUDY SELECTION: We included RCTs comparing NIV with any comparator (standard oxygen therapy and high-flow nasal cannula [HFNC]) in pediatric patients with ARF. We excluded studies performed on neonates and on chronic respiratory failure patients. DATA EXTRACTION: Baseline characteristics, intubation rate, mortality, and hospital and ICU length of stays were extracted by trained investigators. DATA SYNTHESIS: We identified 15 RCTs (2,679 patients) for the final analyses. The intubation rate was 109 of 945 (11.5%) in the NIV group, and 158 of 1,086 (14.5%) in the control group (risk ratio, 0.791; 95% CI, 0.629-0.996; p = 0.046; I2 = 0%; number needed to treat = 31). Findings were strengthened after removing studies with intervention duration shorter than an hour and after excluding studies with cross-over as rescue treatment. There was no difference in mortality, and ICU and hospital length of stays. CONCLUSIONS: In pediatric patients, NIV applied for ARF might reduce the intubation rate compared with standard oxygen therapy or HFNC. No difference in mortality was observed.

Non-Invasive Ventilation in the Prehospital Emergency Setting: A Systematic Review and Meta-Analysis.

INTRODUCTION: Noninvasive ventilation is a well-established treatment for acute respiratory failure, being increasingly applied in the prehospital setting. This systematic review and meta-analysis aims to investigate whether early prehospital initiation of noninvasive ventilation reduces mortality compared to standard oxygen therapy. METHODS: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to February 7th, 2022, for studies comparing prehospital noninvasive ventilation performed by emergency medical services versus standard oxygen therapy in patients with acute respiratory failure. The primary outcome was mortality at the longest follow-up available. RESULTS: We included ten randomized studies and two quasi-randomized studies for a total of 1485 patients. Prehospital treatment with noninvasive ventilation compared with standard oxygen therapy did not significantly reduce mortality at the longest follow-up available (107/810 [13%] vs 114/772 [15%]; RR = 0.89; 95% CI, 0.70-1.13; P = 0.34; I2=24%). The endotracheal intubation rate was reduced when receiving prehospital noninvasive ventilation (38/776 [4.9%] vs 81/743 [11%]; RR = 0.44; 95% CI, 0.31-0.63; P < 0.001; I2=0%; number needed to treat 17). The intensive care admission rate (114/532 [21%] vs 129/507 [25%]; RR = 0.85; 95% CI, 0.69-1.04; P = 0.11; I2=0%) and length of hospital stay (mean difference=-1.29 days; 95% CI, -3.35-0.77; P = 0.21; I2=82%) were similar between groups. CONCLUSIONS: Adults with acute respiratory failure treated in the prehospital setting with noninvasive ventilation had a lower risk of intubation than those managed with standard oxygen therapy, with similar risk of death, intensive care admission, and length of hospital stay. REVIEW REGISTRATION: PROSPERO CRD42021284947.

Association of COVID-19 Vaccinations With Intensive Care Unit Admissions and Outcome of Critically Ill Patients With COVID-19 Pneumonia in Lombardy, Italy.

Importance: Data on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2-related pneumonia are scarce. Objective: To evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU. Design, Setting, and Participants: This retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021. Exposures: COVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine). Main Outcomes and Measures: The incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders. Results: Among the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] age was 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dose was 0.03 (95% CI, 0.03-0.04; P < .001), whereas IRR of individuals who received an adenoviral vector vaccine after 120 days was 0.21 (95% CI, 0.19-0.24; P < .001). There were 553 patients admitted to an ICU for COVID-19 pneumonia during the study period: 139 patients (25.1%) were vaccinated and 414 (74.9%) were unvaccinated. Compared with unvaccinated patients, vaccinated patients were older (median [IQR]: 72 [66-76] vs 60 [51-69] years; P < .001), primarily male individuals (110 patients [79.1%] vs 252 patients [60.9%]; P < .001), with more comorbidities (median [IQR]: 2 [1-3] vs 0 [0-1] comorbidities; P < .001) and had higher ratio of arterial partial pressure of oxygen (Pao2) and fraction of inspiratory oxygen (FiO2) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P = .007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower Pao2/FiO2 at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients. Conclusions and Relevance: In this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status. These findings suggest a substantial reduction of the risk of developing COVID-19-related severe acute respiratory failure requiring ICU admission among vaccinated people.

Effects on health-related quality of life of interventions affecting survival in critically ill patients: a systematic review.

Survival has been considered the cornerstone for clinical outcome evaluation in critically ill patients admitted to intensive care unit (ICU). There is evidence that ICU survivors commonly show impairments in long-term outcomes such as quality of life (QoL) considering them as the most relevant ones. In the last years, the concept of patient-important outcomes has been introduced and increasingly reported in peer-reviewed publications. In the present systematic review, we evaluated how many randomized controlled trials (RCTs) were conducted on critically ill patients and reporting a benefit on survival reported also data on QoL. All RCTs investigating nonsurgical interventions that significantly reduced mortality in critically ill patients were searched on MEDLINE/PubMed, Scopus and Embase from inception until August 2021. In a second stage, for all the included studies, the outcome QoL was investigated. The primary outcome was to evaluate how many RCTs analyzing interventions reducing mortality reported also data on QoL. The secondary endpoint was to investigate if QoL resulted improved, worsened or not modified. Data on QoL were reported as evaluated outcome in 7 of the 239 studies (2.9%). The tools to evaluate QoL and QoL time points were heterogeneous. Four interventions showed a significant impact on QoL: Two interventions improved survival and QoL (pravastatin in subarachnoid hemorrhage, dexmedetomidine in elderly patients after noncardiac surgery), while two interventions reduced mortality but negatively influenced QoL (caloric restriction in patients with refeeding syndrome and systematic ICU admission in elderly patients). In conclusion, only a minority of RCTs in which an intervention demonstrated to affect mortality in critically ill patients reported also data on QoL. Future research in critical care should include patient-important outcomes like QoL besides mortality. Data on this topic should be collected in conformity with PROs statement and core outcome sets to guarantee quality and comparability of results.

Continuous positive airway pressure and pronation outside the Intensive Care Unit in COVID-19 acute respiratory distress syndrome.

BACKGROUND: The efficacy and safety of continuous positive airway pressure and respiratory physiotherapy outside the Intensive Care Unit during a pandemic. METHODS: In this cohort study performed in February-May 2020 in a large teaching hospital in Milan, COVID-19 patients with adult respiratory distress syndrome receiving continuous positive airway pressure (positive end-expiratory pressure =10 cm H2O, FiO2=0.6, daily treatment duration: 4×3h-cycles) and respiratory physiotherapy including pronation outside the Intensive Care Unit were followed-up. RESULTS: Of 90 acute respiratory distress syndrome (ARDS) patients treated with continuous positive airway pressure (45/90, 50% pronated at least once) outside the Intensive Care Unit and with a median (interquartile) follow-up of 37 (11-46) days, 45 (50%) were discharged at home, 28 (31%) were still hospitalized, and 17 (19%) died. Continuous positive airway pressure failure was recorded for 35 (39%) patients. Patient mobilization was associated with reduced failure rates (P=0.033). No safety issues were observed. CONCLUSIONS: Continuous positive airway pressure with patient mobilization (including pronation) was effective and safe in patients with ARDS due to COVID-19 managed outside the Intensive Care Unit setting during the pandemic.

The ABCDE bundle implementation in an intensive care unit: Facilitators and barriers perceived by nurses and doctors.

AIM: To describe the facilitators and barriers perceived by healthcare teams after the implementation of the Awakening, Breathing, Coordination, Delirium monitoring/management and Early mobility bundle in an intensive care unit in Italy. This multicomponent intervention strategy has been associated with lower probabilities of delirium, improved functional outcomes and shorter duration of mechanical ventilation. METHODS: A survey study conducted between June 2015 and May 2016 explored variables related to intensive care unit team members: perceptions of delirium; knowledge of the Awakening, Breathing, Coordination, Delirium monitoring/management and Early mobility bundle; teamwork perception and resource availability. RESULTS: Most of the participants affirmed having reasonable knowledge of delirium, outcomes of delirious episodes, Awakening, Breathing, Coordination, Delirium monitoring/management and Early mobility bundle components and their effectiveness. Low coordination between healthcare professionals was identified as a barrier. Overall, the time elapsing from the beginning of implementation of the bundle determined an increase in levels of awareness and confidence in the application of the bundle protocol and the Confusion Assessment Method Intensive Care Unit scale. CONCLUSION: Issues with the Awakening, Breathing, Coordination, Delirium monitoring/management and Early mobility bundle relating to coordination, management and interdisciplinary ward rounds are critical and should be remedied and monitored. This study could provide the basis for improving bundle implementation strategies and surveying levels of progression in other intensive care units.

Perioperative Noninvasive Ventilation After Adult or Pediatric Surgery: A Comprehensive Review.

Postoperative pulmonary complications and acute respiratory failure are among the leading causes of adverse postoperative outcomes. Noninvasive ventilation may safely and effectively prevent acute respiratory failure in high-risk patients after cardiothoracic surgery and after abdominal surgery. Moreover, noninvasive ventilation can be used to treat postoperative hypoxemia, particularly after abdominal surgery. Noninvasive ventilation also can be helpful to prevent or manage intraoperative acute respiratory failure during non-general anesthesia, primarily in patients with poor respiratory function. Finally, noninvasive ventilation is superior to standard preoxygenation in delaying desaturation during intubation in morbidly obese and in critically ill hypoxemic patients. The few available studies in children suggest that noninvasive ventilation could be safe and valuable in treating hypoxemic or hypercapnic acute respiratory failure after cardiac surgery; on the other hand, it could be dangerous after tracheoesophageal correction.

Caring for acute coronary syndrome and other time-sensitive medical emergencies during the coronavirus disease 2019 pandemic in Northern Italy: report from a hub center.

BACKGROUND: The Lombardy region, in Northern Italy, suffered a major outbreak of Coronavirus disease 2019 (COVID-19) at the end of February 2020. The health system was rapidly overwhelmed by the pandemic. It became evident that patients suffering from time-sensitive medical emergencies like stroke, cerebral hemorrhage, trauma and acute myocardial infarction required timely, effective and safe pathways to be treated. The problem was addressed by a regional decree that created a hub-and-spoke system for time-sensitive medical emergencies. METHODS: We report the re-organizational changes adopted at a hub hospital (despite having already destined to COVID-19 patients most resources), and the number of emergent procedures for medical emergencies on the first 30-day of activity. These data were compared with the hospital activity in the same period of the previous year. RESULTS: Organizational changes were implemented in few hours. Dedicated pathways for non-COVID-19 patients affected by a medical emergency were set up in the emergency department, in the labs and in the operating theater. Ten intensive beds were implemented from a high-dependency unit; two operating rooms were reserved 24 h/day to neurosurgical or trauma emergencies. The number of emergent procedures was not different from that of the previous year, no admission refusal, no treatment delay and no viral transmission to the treated patients were recorded. No viral transmission to health care workers was observed. CONCLUSIONS: Re-organization of a hospital in order to adopt a hub-and-spoke model resulted feasible and allowed to face acute coronary syndrome and other time-sensitive medical emergencies timely and safely.

Time course of risk factors associated with mortality of 1260 critically ill patients with COVID-19 admitted to 24 Italian intensive care units.

PURPOSE: To evaluate the daily values and trends over time of relevant clinical, ventilatory and laboratory parameters during the intensive care unit (ICU) stay and their association with outcome in critically ill patients with coronavirus disease 19 (COVID-19). METHODS: In this retrospective-prospective multicentric study, we enrolled COVID-19 patients admitted to Italian ICUs from February 22 to May 31, 2020. Clinical data were daily recorded. The time course of 18 clinical parameters was evaluated by a polynomial maximum likelihood multilevel linear regression model, while a full joint modeling was fit to study the association with ICU outcome. RESULTS: 1260 consecutive critically ill patients with COVID-19 admitted in 24 ICUs were enrolled. 78% were male with a median age of 63 [55-69] years. At ICU admission, the median ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) was 122 [89-175] mmHg. 79% of patients underwent invasive mechanical ventilation. The overall mortality was 34%. Both the daily values and trends of respiratory system compliance, PaO2/FiO2, driving pressure, arterial carbon dioxide partial pressure, creatinine, C-reactive protein, ferritin, neutrophil, neutrophil-lymphocyte ratio, and platelets were associated with survival, while for lactate, pH, bilirubin, lymphocyte, and urea only the daily values were associated with survival. The trends of PaO2/FiO2, respiratory system compliance, driving pressure, creatinine, ferritin, and C-reactive protein showed a higher association with survival compared to the daily values. CONCLUSION: Daily values or trends over time of parameters associated with acute organ dysfunction, acid-base derangement, coagulation impairment, or systemic inflammation were associated with patient survival.

Impact of the COVID-19 outbreak on severe trauma trends and healthcare system reassessment in Lombardia, Italy: an analysis from the regional trauma registry.

BACKGROUNDS: The COVID-19 pandemic drastically strained the health systems worldwide, obligating the reassessment of how healthcare is delivered. In Lombardia, Italy, a Regional Emergency Committee (REC) was established and the regional health system reorganized, with only three hospitals designated as hubs for trauma care. The aim of this study was to evaluate the effects of this reorganization of regional care, comparing the distribution of patients before and during the COVID-19 outbreak and to describe changes in the epidemiology of severe trauma among the two periods. METHODS: A cohort study was conducted using retrospectively collected data from the Regional Trauma Registry of Lombardia (LTR). We compared the data of trauma patients admitted to three hub hospitals before the COVID-19 outbreak (September 1 to November 19, 2019) with those recorded during the pandemic (February 21 to May 10, 2020) in the same hospitals. Demographic data, level of pre-hospital care (Advanced Life Support-ALS, Basic Life Support-BLS), type of transportation, mechanism of injury (MOI), abbreviated injury score (AIS, 1998 version), injury severity score (ISS), revised trauma score (RTS), and ICU admission and survival outcome of all the patients admitted to the three trauma centers designed as hubs, were reviewed. Screening for COVID-19 was performed with nasopharyngeal swabs, chest ultrasound, and/or computed tomography. RESULTS: During the COVID-19 pandemic, trauma patients admitted to the hubs increased (46.4% vs 28.3%, p < 0.001) with an increase in pre-hospital time (71.8 vs 61.3 min, p < 0.01), while observed in hospital mortality was unaffected. TRISS, ISS, AIS, and ICU admission were similar in both periods. During the COVID-19 outbreak, we observed substantial changes in MOI of severe trauma patients admitted to three hubs, with increases of unintentional (31.9% vs 18.5%, p < 0.05) and intentional falls (8.4% vs 1.2%, p < 0.05), whereas the pandemic restrictions reduced road- related injuries (35.6% vs 60%, p < 0.05). Deaths on scene were significantly increased (17.7% vs 6.8%, p < 0.001). CONCLUSIONS: The COVID-19 outbreak affected the epidemiology of severe trauma patients. An increase in trauma patient admissions to a few designated facilities with high level of care obtained satisfactory results, while COVID-19 patients overwhelmed resources of most other hospitals.

Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients.

BACKGROUND: Limited data are available on the use of prone position in intubated, invasively ventilated patients with Coronavirus disease-19 (COVID-19). Aim of this study is to investigate the use and effect of prone position in this population during the first 2020 pandemic wave. METHODS: Retrospective, multicentre, national cohort study conducted between February 24 and June 14, 2020, in 24 Italian Intensive Care Units (ICU) on adult patients needing invasive mechanical ventilation for respiratory failure caused by COVID-19. Clinical data were collected on the day of ICU admission. Information regarding the use of prone position was collected daily. Follow-up for patient outcomes was performed on July 15, 2020. The respiratory effects of the first prone position were studied in a subset of 78 patients. Patients were classified as Oxygen Responders if the PaO2/FiO2 ratio increased ≥ 20 mmHg during prone position and as Carbon Dioxide Responders if the ventilatory ratio was reduced during prone position. RESULTS: Of 1057 included patients, mild, moderate and severe ARDS was present in 15, 50 and 35% of patients, respectively, and had a resulting mortality of 25, 33 and 41%. Prone position was applied in 61% of the patients. Patients placed prone had a more severe disease and died significantly more (45% vs. 33%, p < 0.001). Overall, prone position induced a significant increase in PaO2/FiO2 ratio, while no change in respiratory system compliance or ventilatory ratio was observed. Seventy-eight % of the subset of 78 patients were Oxygen Responders. Non-Responders had a more severe respiratory failure and died more often in the ICU (65% vs. 38%, p = 0.047). Forty-seven % of patients were defined as Carbon Dioxide Responders. These patients were older and had more comorbidities; however, no difference in terms of ICU mortality was observed (51% vs. 37%, p = 0.189 for Carbon Dioxide Responders and Non-Responders, respectively). CONCLUSIONS: During the COVID-19 pandemic, prone position has been widely adopted to treat mechanically ventilated patients with respiratory failure. The majority of patients improved their oxygenation during prone position, most likely due to a better ventilation perfusion matching. TRIAL REGISTRATION: clinicaltrials.gov number: NCT04388670.

Continuous infusion versus intermittent administration of meropenem in critically ill patients (MERCY): A multicenter randomized double-blind trial. Rationale and design.

OBJECTIVE: Meropenem is a ß-lactam, carbapenem antibacterial agent with antimicrobial activity against gram-negative, gram-positive and anaerobic micro-organisms and is important in the empirical treatment of serious infections in Intensive Care Unit (ICU) patients. Multi-drug resistant gram-negative organisms, coupled with scarcity of new antibiotic classes, forced healthcare community to optimize the therapeutic potential of available antibiotics. Our aim is to investigate the effect of continuous infusion of meropenem against bolus administration, as indicated by a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens in a population of ICU patients. DESIGN: Double blind, double dummy, multicenter randomized controlled trial (1:1 allocation ratio). SETTING: Tertiary and University hospitals. INTERVENTIONS: 600 ICU patients with sepsis or septic shock, needing by clinical judgment antibiotic therapy with meropenem, will be randomized to receive a continuous infusion of meropenem 3 g/24 h or an equal dose divided into three daily boluses (i.e. 1g q8h). MEASUREMENTS: The primary endpoint will be a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens. Secondary endpoints will be death from any cause at day 90, antibiotic-free days at day 28, ICU-free days at day 28, cumulative SOFA-free (Sequential Organ Failure Assessment) score from randomization to day 28 and the two, separate, components of the primary endpoint. We expect a primary outcome reduction from 52 to 40% in the continuous infusion group. CONCLUSIONS: The trial will provide evidence for choosing intermittent or continuous infusion of meropenem for critically ill patients with multi-drug resistant gram-negative infections.

SARS-CoV-2 on Ocular Surfaces in a Cohort of Patients With COVID-19 From the Lombardy Region, Italy.

Importance: Since February 2020, coronavirus disease 2019 (COVID-19) has spread rapidly all over the world, with an epidemiological cluster in Lombardy, Italy. The viral communicability may be mediated by various body fluids, but insufficient information is available on the presence of the virus in human tears. Objectives: To investigate the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears collected from patients with COVID-19 by means of real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) assay and to assess the association of virus presence with concomitant clinical conditions. Design, Setting, and Participants: Cross-sectional study conducted between April 9 and May 5, 2020. The setting was intensive care units at Azienda Socio-Sanitaria Territoriale (ASST) Sette-Laghi Hospital, University of Insubria, in Varese, Lombardy, Italy. A conjunctival swab was performed in 91 patients hospitalized for COVID-19, which was clinically diagnosed by rRT-PCR assay on nasopharyngeal swabs and by radiological imaging. Conjunctival swabs from 17 additional healthy volunteer participants with no symptoms of COVID-19 were examined to evaluate the availability and applicability of the conjunctival swab test. Exposure: SARS-CoV-2 detection by means of rRT-PCR assay performed on the collected samples obtained by conjunctival swabs. Main Outcomes and Measures: Conjunctival swab and nasopharyngeal swab results are reported, as well as demographic and clinical data. Results: A total of 108 participants (mean [SD] age, 58.7 [14.2] years; 55 female and 53 male) were tested for SARS-CoV-2 using rRT-PCR assay, including 91 patients hospitalized with COVID-19 and 17 were healthy volunteers. SARS-CoV-2 was found on the ocular surface in 52 of 91 patients with COVID-19 (57.1%; 95% CI, 46.3%-67.5%), with a wide variability in the mean viral load from both eyes. Among a subset of 41 patients, concordance of 63.0% (95% CI, 41.0%-81.0%) was found between positive conjunctival and nasopharyngeal swab test results when performed within 2 days of each other. In 17 of these patients, nasopharyngeal swab results were negative for SARS-CoV-2. In 10 of these 17 patients, conjunctival swab results were positive for the virus. Conclusions and Relevance: In this study, SARS-CoV-2 RNA was found on the ocular surface in a large part of this cohort of patients with COVID-19, although the infectivity of this material could not be determined. Because patients may have positive test results with a conjunctival swab and negative results with a nasopharyngeal swab, use of the slightly invasive conjunctival swab may be considered as a supplementary diagnostic test.