Invasive pulmonary aspergillosis in the COVID-19 era: An expected new entity.

OBJECTIVES: Information on the recently COVID-19-associated pulmonary aspergillosis (CAPA) entity is scarce. We describe eight CAPA patients, compare them to colonised ICU patients with coronavirus disease 2019 (COVID-19), and review the published literature from Western countries. METHODS: Prospective study (March to May, 2020) that included all COVID-19 patients admitted to a tertiary hospital. Modified AspICU and European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria were used. RESULTS: COVID-19-associated pulmonary aspergillosis was diagnosed in eight patients (3.3% of 239 ICU patients), mostly affected non-immunocompromised patients (75%) with severe acute respiratory distress syndrome (ARDS) receiving corticosteroids. Diagnosis was established after a median of 15 days under mechanical ventilation. Bronchoalveolar lavage was performed in two patients with positive Aspergillus fumigatus cultures and galactomannan (GM) index. Serum GM was positive in 4/8 (50%). Thoracic CT scan findings fulfilled EORTC/MSG criteria in one case. Isavuconazole was used in 4/8 cases. CAPA-related mortality was 100% (8/8). Compared with colonised patients, CAPA subjects were administered tocilizumab more often (100% vs. 40%, p = .04), underwent longer courses of antibacterial therapy (13 vs. 5 days, p = .008), and had a higher all-cause mortality (100% vs. 40%, p = .04). We reviewed 96 similar cases from recent publications: 59 probable CAPA (also putative according modified AspICU), 56 putative cases and 13 colonisations according AspICU algorithm; according EORTC/MSG six proven and two probable. Overall, mortality in the reviewed series was 56.3%. CONCLUSIONS: COVID-19-associated pulmonary aspergillosis must be considered a serious and potentially life-threatening complication in patients with severe COVID-19 receiving immunosuppressive treatment.

Severe 2009 A/H1N1v influenza in pregnant women in Spain.

OBJECTIVES: To describe the severity of the 2009 influenza A/H1N1v illness among pregnant women admitted to Spanish intensive care units. DESIGN AND PATIENTS: Prospective, observational, multicenter study conducted in 148 Spanish intensive care units. We reviewed demographic and clinical data from the Spanish Society of Intensive Care Medicine database reported from April 23, 2009, to February 15, 2010. We included women of reproductive age (15-44 yrs) with confirmed A/H1N1v infection admitted to intensive care units. MAIN RESULTS: Two hundred thirty-four women of reproductive age were admitted to intensive care units, 50 (21.4%) of them pregnant. Seven deaths were recorded in pregnant and 22 in nonpregnant women. Among intensive care unit admissions, there were no statistically significant differences between pregnant women and nonpregnant in Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment scores, chest x-rays, inotrope requirement, or need for mechanical ventilation or steroid therapy. Mortality risk was significantly associated with Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and obesity. Viral pneumonia was more frequent in pregnant women than in nonpregnant women, with an odds ratio (adjusted for asthma, time from onset influenza symptoms to hospital admission and obesity) of 4.9 (95% confidence interval: 1.4-17.2). The development of primary viral pneumonia in women of reproductive age appeared to be related to the time of commencement of antiviral treatment, the lowest rates being reported with initiation of antiviral therapy within 48 hrs of symptom onset (63.6% vs. 82.6%, p = .03). However, antiviral therapy was started within this time span in only 14% of pregnant women. CONCLUSIONS: More than 20% of women of reproductive age admitted to intensive care unit for pH1N1 infection were pregnant. Pregnancy was significantly associated with primary viral pneumonia. Pregnant women should receive prompt treatment with oseltamivir within 48 hrs of the onset of influenza symptoms.

Pandemic and post-pandemic influenza A (H1N1) infection in critically ill patients.

BACKGROUND: There is a vast amount of information published regarding the impact of 2009 pandemic Influenza A (pH1N1) virus infection. However, a comparison of risk factors and outcome during the 2010-2011 post-pandemic period has not been described. METHODS: A prospective, observational, multi-center study was carried out to evaluate the clinical characteristics and demographics of patients with positive RT-PCR for H1N1 admitted to 148 Spanish intensive care units (ICUs). Data were obtained from the 2009 pandemic and compared to the 2010-2011 post-pandemic period. RESULTS: Nine hundred and ninety-seven patients with confirmed An/H1N1 infection were included. Six hundred and forty-eight patients affected by 2009 (pH1N1) virus infection and 349 patients affected by the post-pandemic Influenza (H1N1)v infection period were analyzed. Patients during the post-pandemic period were older, had more chronic comorbid conditions and presented with higher severity scores (Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA)) on ICU admission. Patients from the post-pandemic Influenza (H1N1)v infection period received empiric antiviral treatment less frequently and with delayed administration. Mortality was significantly higher in the post-pandemic period. Multivariate analysis confirmed that haematological disease, invasive mechanical ventilation and continuous renal replacement therapy were factors independently associated with worse outcome in the two periods. HIV was the only new variable independently associated with higher ICU mortality during the post-pandemic Influenza (H1N1)v infection period. CONCLUSION: Patients from the post-pandemic Influenza (H1N1)v infection period had an unexpectedly higher mortality rate and showed a trend towards affecting a more vulnerable population, in keeping with more typical seasonal viral infection.

Possible unrecognised liver injury is associated with mortality in critically ill COVID-19 patients.

BACKGROUND: Coronavirus disease (COVID-19) with acute respiratory distress syndrome is a life-threatening condition. A previous diagnosis of chronic liver disease is associated with poorer outcomes. Nevertheless, the impact of silent liver injury has not been investigated. We aimed to explore the association of pre-admission liver fibrosis indices with the prognosis of critically ill COVID-19 patients. METHODS: The work presented was an observational study in 214 patients with COVID-19 consecutively admitted to the intensive care unit (ICU). Pre-admission liver fibrosis indices were calculated. In-hospital mortality and predictive factors were explored with Kaplan-Meier and Cox regression analysis. RESULTS: The mean age was 59.58 (13.79) years; 16 patients (7.48%) had previously recognised chronic liver disease. Up to 78.84% of patients according to Forns, and 45.76% according to FIB-4, had more than minimal fibrosis. Fibrosis indices were higher in non-survivors [Forns: 6.04 (1.42) versus 4.99 (1.58), p < 0.001; FIB-4: 1.77 (1.17) versus 1.41 (0.91), p = 0.020)], but no differences were found in liver biochemistry parameters. Patients with any degree of fibrosis either by Forns or FIB-4 had a higher mortality, which increased according to the severity of fibrosis (p < 0.05 for both indexes). Both Forns [HR 1.41 (1.11-1.81); p = 0.006] and FIB-4 [HR 1.31 (0.99-1.72); p = 0.051] were independently related to survival after adjusting for the Charlson comorbidity index, APACHE II, and ferritin. CONCLUSION: Unrecognised liver fibrosis, assessed by serological tests prior to admission, is independently associated with a higher risk of death in patients with severe COVID-19 admitted to the ICU.

Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study.

BACKGROUND: Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients. METHODS: Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 106 (IQR 0.50 × 106) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters. FINDINGS: First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement. INTERPRETATION: Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects. FUNDING: None.

Clinical characteristics, evolution, and treatment-related risk factors for mortality among immunosuppressed patients with influenza A (H1N1) virus admitted to the intensive care unit.

PURPOSE: Information about immunocompromised patients infected with influenza A (H1N1) virus and requiring admission to the ICU is lacking. Our objective was to know the clinical characteristics of these patients and to identify treatment-related variables associated with mortality. MATERIAL AND METHODS: A prospective multicenter observational cohort study was based on data from a Spanish registry (2009-2015) collected by 148 Spanish ICUs. All patients admitted to the ICU with the diagnosis of influenza A (H1N1) virus infection were included. Immunosuppression was clearly defined. Factors associated with mortality in immunocompromised patients were assessed by conventional logistic regression analysis and by a propensity score (PS) adjusted-multivariable analysis. RESULTS: Of 1899 patients with influenza A (H1N1) infection, 238 (12.5%) were classified as immunocompromised. Mortality was significantly higher in immunosuppressed patients. Four variables independently associated with mortality were identified: SOFA score, need of vasopressor, use of corticosteroids, and acute renal failure, AKIN 3 stage. In the PS-adjusted model, corticosteroid therapy remained as an independent factor associated with increased mortality (OR 2.25;95%CI, 1.15-4.38;p = 0.017). In the subgroup of hematological patients (n = 141), corticosteroid therapy was also associated with increased mortality (OR 3.12; 95%CI, 1.32-7.41; p = 0.010). CONCLUSION: Immunocompromised individuals with influenza A (H1N1) admitted to the ICU have a poor outcome. In this population, the use of corticosteroids is strongly discouraged.

Clinical factors associated with inappropriate prophylaxis of venous thromboembolic disease in critically ill patients. A single day cross-sectional study.

PURPOSE: A poor implementation of VTE prophylactic measures recommended for critically ill patients has been observed in several epidemiological studies. The clinical factors associated with this have not been clearly established. The objective of our study was to identify which factors could be related to the inappropriate use of VTE prophylaxis. METHODS: Analytic epidemiological study based on different aspects of VTE prophylaxis performed on Spanish ICU patients. A multiple logistic regression analysis was conducted to identify the risk factors associated with inappropriate prophylaxis, according to the American College of Chest Physicians 2012 guidelines. RESULTS: We enrolled 777 patients. On admission, 62% presented medical, 30% surgical and 8% major trauma pathology. Of all patients, 41% were receiving an inappropriate prophylaxis, including 19% which did not receive any prophylaxis. The presence of a contraindication for pharmacological prophylaxis (OR 3.91, 95% CI 2.50-6.10) and non-medical pathology at ICU admission (OR 11.09; 95% CI 7.63-16.12) were associated with inappropriate prophylaxis. In contrast, mechanical ventilation (OR 0.70, 95% CI 0.45-0.98), bed rest>48h (OR 0.61, 95% CI 0.49-0.98), the use of a protocol for VTE prophylaxis (OR 0.66, 95% CI 0.45-0.98) and a VTE risk scoring system (OR 0.49, 95% CI 0.24-0.98) were associated with adequate prophylaxis. CONCLUSIONS: Our study highlighted a poor compliance with the VTE prophylaxis recommendations proposed for critical patients. The implementation of specific protocols for prophylaxis that include a correct evaluation according to VTE and haemorrhage risk, would allow for optimisation of mechanical and combined prophylaxis, improving adherence to the clinical practice guidelines.

PROF-ETEV study: prophylaxis of venous thromboembolic disease in critical care units in Spain.

PURPOSE: Venous thromboembolic disease (VTE) in critically ill patients has a high incidence despite prophylactic measures. This fact could be related to an inappropriate use of these measures due to the absence of specific VTE risk scores. To assess the current situation in Spain, we have performed a cross-sectional study, analyzing if the prophylactic measures were appropriate to the patients' VTE risk. METHODS: Through an electronic questionnaire, we carried out a single day point prevalence study on the VTE prophylactic measures used in several critical care units in Spain. We performed a risk stratification for VTE in three groups: low, moderate-high, and very high risk. The American College of Chest Physicians guidelines were used to determine if the patients were receiving the recommended prophylaxis. RESULTS: A total of 777 patients were included; 62% medical, 30% surgical, and 7% major trauma patients. The median number of the risk factors for VTE was four. According to the proposed VTE risk score, only 2% of the patients were at low risk, whereas 83% were at very high risk. Sixty-three percent of patients received pharmacological prophylaxis, 12% mechanical prophylaxis, 6% combined prophylaxis, and 19% did not receive any prophylactic measure. According to criteria suggested by the guidelines, 23% of medical, 71% of surgical, and 70% of major trauma patients received an inappropriate prophylaxis. CONCLUSIONS: Most critically ill patients are at high or very high risk of VTE, but there is a low rate of appropriate prophylaxis. The efforts to improve the identification of patients at risk, and the implementation of appropriate prevention protocols should be enhanced.

Corticosteroid therapy in patients with primary viral pneumonia due to pandemic (H1N1) 2009 influenza.

OBJECTIVE: During the first pandemic, some patients with pandemic (H1N1) 2009 influenza were treated with corticosteroids. The objective of this study was to assess the effect on survival of corticosteroid therapy in patients with pandemic (H1N1) 2009 influenza. METHODS: Prospective, observational, multicenter study performed in 148 ICU. Data were recorded in the GTEI/SEMICYUC registry. Adult patients with pandemic (H1N1) 2009 influenza confirmed by rt-PCR were included in the analysis. Database records specified corticosteroid type and reason for corticosteroid treatment. RESULTS: 372 patients with the diagnosis of primary viral pneumonia and completed outcomes treated in an ICU were included in the database. Mechanical ventilation was used in 70.2% of the patients. 136 (36.6%) patients received corticosteroids after a diagnosis of primary viral pneumonia. Obesity (35.6% vs 47.8% p = 0.021) and asthma (7.6% vs 15.4% p = 0.018), were more frequent in the group treated with corticosteroids. A Cox regression analysis adjusted for severity and potential confounding factors found that the use of corticosteroid therapy was not significantly associated with mortality (HR = 1.06, 95% CI 0.626-1.801; p = 0.825). CONCLUSIONS: Corticosteroid therapy in a selected group of patients with primary viral pneumonia due to pandemic (H1N1) 2009 influenza does not improve survival.

[Department of anesthesia, resuscitation and critical care]. / Departamento de anestesia, reanimación y cuidados intensivos.

The present study describes the impact on the Department of Anesthesiology, Resuscitation and Critical Care of treating the victims of the 11 March terrorist attack, both on the day of the attack and on subsequent days. Of the 182 victims who were hospitalized, 61 had a poor prognosis, 24 had a very poor prognosis, 2 were already dead, and a further 2 died that day. Twenty-seven patients were admitted to the critical care unit. Patients with suspected severe injuries were sent to postanesthesia recovery units, where a second level of triage was performed, allowing patients to be appropriately transferred according to their severity and the necessary interventions to be performed.