Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
1.
JAMA ; 323(16): 1574-1581, 2020 04 28.
Article in English | MEDLINE | ID: covidwho-1453471

ABSTRACT

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%.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Critical Care/statistics & numerical data , Hospital Mortality , Intensive Care Units/statistics & numerical data , Pneumonia, Viral/epidemiology , Positive-Pressure Respiration/statistics & numerical data , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , COVID-19 , Comorbidity , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Critical Illness/therapy , Female , Hospitalization , Humans , Italy/epidemiology , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , Sex Distribution , Young Adult
2.
Intensive Care Med ; 47(9): 995-1008, 2021 09.
Article in English | MEDLINE | ID: covidwho-1349283

ABSTRACT

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.


Subject(s)
COVID-19 , Critical Illness , Aged , Humans , Intensive Care Units , Italy , Male , Middle Aged , Prospective Studies , Respiration, Artificial , Retrospective Studies , Risk Factors , SARS-CoV-2
3.
Sci Rep ; 11(1): 10103, 2021 05 12.
Article in English | MEDLINE | ID: covidwho-1226438

ABSTRACT

COVID-19 infection may predispose to secondary bacterial infection which is associated with poor clinical outcome especially among critically ill patients. We aimed to characterize the lower respiratory tract bacterial microbiome of COVID-19 critically ill patients in comparison to COVID-19-negative patients. We performed a 16S rRNA profiling on bronchoalveolar lavage (BAL) samples collected between April and May 2020 from 24 COVID-19 critically ill subjects and 24 patients with non-COVID-19 pneumonia. Lung microbiome of critically ill patients with COVID-19 was characterized by a different bacterial diversity (PERMANOVA on weighted and unweighted UniFrac Pr(> F) = 0.001) compared to COVID-19-negative patients with pneumonia. Pseudomonas alcaligenes, Clostridium hiranonis, Acinetobacter schindleri, Sphingobacterium spp., Acinetobacter spp. and Enterobacteriaceae, characterized lung microbiome of COVID-19 critically ill patients (LDA score > 2), while COVID-19-negative patients showed a higher abundance of lung commensal bacteria (Haemophilus influenzae, Veillonella dispar, Granulicatella spp., Porphyromonas spp., and Streptococcus spp.). The incidence rate (IR) of infections during COVID-19 pandemic showed a significant increase of carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection. In conclusion, SARS-CoV-2 infection and antibiotic pressure may predispose critically ill patients to bacterial superinfection due to opportunistic multidrug resistant pathogens.


Subject(s)
Bacteria/isolation & purification , COVID-19/microbiology , Dysbiosis/microbiology , Lung/microbiology , Aged , Bronchoalveolar Lavage Fluid/microbiology , COVID-19/diagnosis , Critical Illness , Dysbiosis/complications , Female , Humans , Male , Microbiota , Middle Aged , SARS-CoV-2/isolation & purification
4.
Chest ; 160(2): 454-465, 2021 08.
Article in English | MEDLINE | ID: covidwho-1184884

ABSTRACT

BACKGROUND: Few small studies have described hospital-acquired infections (HAIs) occurring in patients with COVID-19. RESEARCH QUESTION: What characteristics in critically ill patients with COVID-19 are associated with HAIs and how are HAIs associated with outcomes in these patients? STUDY DESIGN AND METHODS: Multicenter retrospective analysis of prospectively collected data including adult patients with severe COVID-19 admitted to eight Italian hub hospitals from February 20, 2020, through May 20, 2020. Descriptive statistics and univariate and multivariate Weibull regression models were used to assess incidence, microbial cause, resistance patterns, risk factors (ie, demographics, comorbidities, exposure to medication), and impact on outcomes (ie, ICU discharge, length of ICU and hospital stays, and duration of mechanical ventilation) of microbiologically confirmed HAIs. RESULTS: Of the 774 included patients, 359 patients (46%) demonstrated 759 HAIs (44.7 infections/1,000 ICU patient-days; 35% multidrug-resistant [MDR] bacteria). Ventilator-associated pneumonia (VAP; n = 389 [50%]), bloodstream infections (BSIs; n = 183 [34%]), and catheter-related BSIs (n = 74 [10%]) were the most frequent HAIs, with 26.0 (95% CI, 23.6-28.8) VAPs per 1,000 intubation-days, 11.7 (95% CI, 10.1-13.5) BSIs per 1,000 ICU patient-days, and 4.7 (95% CI, 3.8-5.9) catheter-related BSIs per 1,000 ICU patient-days. Gram-negative bacteria (especially Enterobacterales) and Staphylococcus aureus caused 64% and 28% of cases of VAP, respectively. Variables independently associated with infection were age, positive end expiratory pressure, and treatment with broad-spectrum antibiotics at admission. Two hundred thirty-four patients (30%) died in the ICU (15.3 deaths/1,000 ICU patient-days). Patients with HAIs complicated by septic shock showed an almost doubled mortality rate (52% vs 29%), whereas noncomplicated infections did not affect mortality. HAIs prolonged mechanical ventilation (median, 24 days [interquartile range (IQR), 14-39 days] vs 9 days [IQR, 5-13 days]; P < .001), ICU stay (24 days [IQR, 16-41 days] vs 9 days [IQR, 6-14 days]; P = .003), and hospital stay (42 days [IQR, 25-59 days] vs 23 days [IQR, 13-34 days]; P < .001). INTERPRETATION: Critically ill patients with COVID-19 are at high risk for HAIs, especially VAPs and BSIs resulting from MDR organisms. HAIs prolong mechanical ventilation and hospitalization, and HAIs complicated by septic shock almost double mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04388670; URL: www.clinicaltrials.gov.


Subject(s)
COVID-19/complications , Cross Infection/complications , Aged , Critical Illness , Cross Infection/epidemiology , Female , Humans , Male , Middle Aged , Pneumonia, Ventilator-Associated/complications , Pneumonia, Ventilator-Associated/epidemiology , Retrospective Studies , Sepsis/complications , Sepsis/epidemiology
5.
Chest ; 159(4): 1426-1436, 2021 04.
Article in English | MEDLINE | ID: covidwho-921554

ABSTRACT

BACKGROUND: Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. RESEARCH QUESTION: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? STUDY DESIGN AND METHODS: We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. RESULTS: Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, -7%; 95% CI, -18% to 4%; P = .015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P = .852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P = .337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P = .300) for the sigh vs no-sigh group. INTERPRETATION: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03201263; URL: www.clinicaltrials.gov.


Subject(s)
Positive-Pressure Respiration , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/therapy , Aged , Female , Humans , Intubation, Intratracheal , Male , Middle Aged , Pilot Projects , Respiratory Distress Syndrome/physiopathology , Respiratory Insufficiency/physiopathology , Respiratory Mechanics
6.
Crit Care ; 25(1): 128, 2021 04 06.
Article in English | MEDLINE | ID: covidwho-1169981

ABSTRACT

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.


Subject(s)
COVID-19/therapy , Critical Care/standards , Intubation/standards , Patient Positioning/standards , Prone Position , Respiration, Artificial/standards , Supine Position , Aged , Cohort Studies , Female , Humans , Italy , Male , Middle Aged , Practice Guidelines as Topic , Retrospective Studies
8.
Trials ; 21(1): 724, 2020 Aug 17.
Article in English | MEDLINE | ID: covidwho-717548

ABSTRACT

OBJECTIVES: To assess the hypothesis that an adjunctive therapy with methylprednisolone and unfractionated heparin (UFH) or with methylprednisolone and low molecular weight heparin (LMWH) are more effective in reducing any-cause mortality in critically-ill ventilated patients with pneumonia from SARS-CoV-2 infection compared to LMWH alone. TRIAL DESIGN: The study is designed as a multi-centre, interventional, parallel group, superiority, randomized, investigator sponsored, three arms study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned to one of the three treatment groups in a ratio 1:1:1. PARTICIPANTS: Inpatients will be recruited from 8 Italian Academic and non-Academic Intensive Care Units INCLUSION CRITERIA (ALL REQUIRED): 1. Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material) 2. Positive pressure ventilation (either non-invasive or invasive) from > 24 hours 3. Invasive mechanical ventilation from < 96 hours 4. PaO2/FiO2 ratio lower than 150 mmHg 5. D-dimer level > 6 times the upper limit of normal reference range 6. C-reactive Protein > 6-fold upper the limit of normal reference range EXCLUSION CRITERIA: 1. Age < 18 years 2. On-going treatment with anticoagulant drugs 3. Platelet count < 100.000/mm3 4. History of heparin-induced thrombocytopenia 5. Allergy to sodium enoxaparin or other LMWH, UFH or methylprednisolone 6. Active bleeding or on-going clinical condition deemed at high risk of bleeding contraindicating anticoagulant treatment 7. Recent (in the last 1 month prior to randomization) brain, spinal or ophthalmic surgery 8. Chronic assumption or oral corticosteroids 9. Pregnancy or breastfeeding or positive pregnancy test. In childbearing age women, before inclusion, a pregnancy test will be performed if not available 10. Clinical decision to withhold life-sustaining treatment or "too sick to benefit" 11. Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition) 12. Lack or withdrawal of informed consent INTERVENTION AND COMPARATOR: • LMWH group: patients in this group will be administered enoxaparin at standard prophylactic dosage. • LMWH + steroid group: patients in this group will receive enoxaparin at standard prophylactic dosage and methylprednisolone. • UFH + steroid group: patients in this group will receive UFH at therapeutic dosages and methylprednisolone. UFH will be administered intravenously in UFH + steroid group at therapeutic doses. The infusion will be started at an infusion rate of 18 UI/kg/hour and then modified to obtain aPTT Ratio in between the range of 1.5-2.0. aPTT will be periodically checked at intervals no longer than 12 hours. The treatment with UFH will be administered up to ICU discharge. After ICU discharge anticoagulant therapy may be interrupted or switched to prophylaxis with LMWH in the destination ward up to clinical judgement of the attending physician. Enoxaparin will be administered in both LMWH group and LMWH + steroid group at standard prophylactic dose (i.e., 4000 UI once day, increased to 6000 UI once day for patients weighting more than 90 kg). The treatment will be administered subcutaneously once a day up to ICU discharge. After ICU discharge it may be continued or interrupted in the destination ward up to clinical judgement of the attending physician. Methylprednisolone will be administered in both LMWH + steroid group and UHF + steroid group intravenously with an initial bolus of 0,5 mg/kg followed by administration of 0,5 mg/kg 4 times daily for 7 days, 0,5 mg/kg 3 times daily from day 8 to day 10, 0,5 mg/kg 2 times daily at days 11 and 12 and 0,5 mg/kg once daily at days 13 and 14. MAIN OUTCOMES: Primary Efficacy Endpoint: All-cause mortality at day 28 Secondary Efficacy Endpoints: - Ventilation free days (VFDs) at day 28, defined as the total number of days that patient is alive and free of ventilation (either invasive or non-invasive) between randomization and day 28 (censored at hospital discharge). - Need of rescue administration of high-dose steroids or immune-modulatory drugs; - Occurrence of switch from non-invasive to invasive mechanical ventilation during ICU stay; - Delay from start of non-invasive ventilation to switch to invasive ventilation; - All-cause mortality at ICU discharge and hospital discharge; - ICU free days (IFDs) at day 28, defined as the total number of days between ICU discharge and day 28. - Occurrence of new infections from randomization to day 28; including infections by Candida, Aspergillus, Adenovirus, Herpes Virus e Cytomegalovirus - Occurrence of new organ dysfunction and grade of dysfunction during ICU stay. - Objectively confirmed venous thromboembolism, stroke or myocardial infarction; Safety endpoints: - Occurrence of major bleeding, defined as transfusion of 2 or more units of packed red blood cells in a day, bleeding that occurs in at least one of the following critical sites [intracranial, intra-spinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal], bleeding that necessitates surgical intervention and bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death); - Occurrence of clinically relevant non-major bleeding, defined ad acute clinically overt bleeding that does not meet the criteria for major and consists of any bleeding compromising hemodynamic; spontaneous hematoma larger than 25 cm2, intramuscular hematoma documented by ultrasonography, haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures; haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention or any other bleeding requiring temporary cessation of a study drug. RANDOMIZATION: A block randomisation will be used with variable block sizes (block size 4-6-8), stratified by 3 factors: Centre, BMI (<30/≥30) and Age (<75/≥75). Central randomisation will be performed using a secure, web-based, randomisation system with an allocation ratio of 1:1:1. The allocation sequence will be generated by the study statistician using computer generated random numbers. BLINDING (MASKING): Participants to the study will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size is based on the hypothesis that the combined use of UHF and steroid versus the LMWH group will significantly reduce the risk of death at day 28. The overall sample size in this study is expected to be 210 with a randomization 1:1:1 and seventy patients in each group. Assuming an alpha of 2.5% (two tailed) and mortality rate in LMWH group of 50%, as indicated from initial studies of ICU patients, the study will have an 80% power to detect at least a 25 % absolute reduction in the risk of death between: a) LMHW + steroid group and LMWH group or b) UHF + steroid group and LMWH group. The study has not been sized to assess the difference between LMHW + steroid group and UHF + steroid group, therefore the results obtained from this comparison will need to be interpreted with caution and will need further adequately sized studies confirm the effect. On the basis of a conservative estimation, that 8 participating sites admit an average of 3 eligible patients per month per centre (24 patients/month). Assuming that 80 % of eligible patients are enrolled, recruitment of 210 participants will be completed in approximately 10 months. TRIAL STATUS: Protocol version 1.1 of April 26th, 2020. Recruitment start (expected): September 1st, 2020 Recruitment finish (expected): June 30th, 2021 TRIAL REGISTRATION: EudraCT number 2020-001921-30 , registered on April 15th, 2020 AIFA approval on May 4th, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Critical Illness , Heparin/administration & dosage , Methylprednisolone/administration & dosage , Pneumonia, Viral/drug therapy , Randomized Controlled Trials as Topic , Respiration, Artificial , Adult , COVID-19 , Heparin/adverse effects , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Methylprednisolone/adverse effects , Pandemics , Partial Thromboplastin Time , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL
...