Non-invasive oxygenation support in acutely hypoxemic COVID-19 patients admitted to the ICU: a multicenter observational retrospective study.

BACKGROUND: Non-invasive oxygenation strategies have a prominent role in the treatment of acute hypoxemic respiratory failure during the coronavirus disease 2019 (COVID-19). While the efficacy of these therapies has been studied in hospitalized patients with COVID-19, the clinical outcomes associated with oxygen masks, high-flow oxygen therapy by nasal cannula and non-invasive mechanical ventilation in critically ill intensive care unit (ICU) patients remain unclear. METHODS: In this retrospective study, we used the best of nine covariate balancing algorithms on all baseline covariates in critically ill COVID-19 patients supported with > 10 L of supplemental oxygen at one of the 26 participating ICUs in Catalonia, Spain, between March 14 and April 15, 2020. RESULTS: Of the 1093 non-invasively oxygenated patients at ICU admission treated with one of the three stand-alone non-invasive oxygenation strategies, 897 (82%) required endotracheal intubation and 310 (28%) died during the ICU stay. High-flow oxygen therapy by nasal cannula (n = 439) and non-invasive mechanical ventilation (n = 101) were associated with a lower rate of endotracheal intubation (70% and 88%, respectively) than oxygen masks (n = 553 and 91% intubated), p < 0.001. Compared to oxygen masks, high-flow oxygen therapy by nasal cannula was associated with lower ICU mortality (hazard ratio 0.75 [95% CI 0.58-0.98), and the hazard ratio for ICU mortality was 1.21 [95% CI 0.80-1.83] for non-invasive mechanical ventilation. CONCLUSION: In critically ill COVID-19 ICU patients and, in the absence of conclusive data, high-flow oxygen therapy by nasal cannula may be the approach of choice as the primary non-invasive oxygenation support strategy.

Individuals With SARS-CoV-2 Infection During the First and Second Waves in Catalonia, Spain: Retrospective Observational Study Using Daily Updated Data.

BACKGROUND: A description of individuals with SARS-CoV-2 infection comparing the first and second waves could help adapt health services to manage this highly transmissible infection. OBJECTIVE: We aimed to describe the epidemiology of individuals with suspected SARS-CoV-2 infection, and the characteristics of patients with a positive test comparing the first and second waves in Catalonia, Spain. METHODS: This study had 2 stages. First, we analyzed daily updated data on SARS-CoV-2 infection in individuals from Girona (Catalonia). Second, we compared 2 retrospective cohorts of patients with a positive reverse-transcription polymerase chain reaction or rapid antigen test for SARS-CoV-2. The severity of patients with a positive test was defined by their admission to hospital, admission to intermediate respiratory care, admission to the intensive care unit, or death. The first wave was from March 1, 2020, to June 24, 2020, and the second wave was from June 25, 2020, to December 8, 2020. RESULTS: The numbers of tests and cases were lower in the first wave than in the second wave (26,096 tests and 3140 cases in the first wave versus 140,332 tests and 11,800 cases in the second wave), but the percentage of positive results was higher in the first wave than in the second wave (12.0% versus 8.4%). Among individuals with a positive diagnostic test, 818 needed hospitalization in the first wave and 680 in the second; however, the percentage of hospitalized individuals was higher in the first wave than in the second wave (26.1% versus 5.8%). The group that was not admitted to hospital included older people and those with a higher percentage of comorbidities in the first wave, whereas the characteristics of the groups admitted to hospital were more alike. CONCLUSIONS: Screening systems for SARS-CoV-2 infection were scarce during the first wave, but were more adequate during the second wave, reflecting the usefulness of surveillance systems to detect a high number of asymptomatic infected individuals and their contacts, to help control this pandemic. The characteristics of individuals with SARS-CoV-2 infection in the first and second waves differed substantially; individuals in the first wave were older and had a worse health condition.

Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study).

PURPOSE: The CIGMA study investigated a novel human polyclonal antibody preparation (trimodulin) containing ~ 23% immunoglobulin (Ig) M, ~ 21% IgA, and ~ 56% IgG as add-on therapy for patients with severe community-acquired pneumonia (sCAP). METHODS: In this double-blind, phase II study (NCT01420744), 160 patients with sCAP requiring invasive mechanical ventilation were randomized (1:1) to trimodulin (42 mg IgM/kg/day) or placebo for five consecutive days. Primary endpoint was ventilator-free days (VFDs). Secondary endpoints included 28-day all-cause and pneumonia-related mortality. Safety and tolerability were monitored. Exploratory post hoc analyses were performed in subsets stratified by baseline C-reactive protein (CRP; ≥ 70 mg/L) and/or IgM (≤ 0.8 g/L). RESULTS: Overall, there was no statistically significant difference in VFDs between trimodulin (mean 11.0, median 11 [n = 81]) and placebo (mean 9.6; median 8 [n = 79]; p = 0.173). Twenty-eight-day all-cause mortality was 22.2% vs. 27.8%, respectively (p = 0.465). Time to discharge from intensive care unit and mean duration of hospitalization were comparable between groups. Adverse-event incidences were comparable. Post hoc subset analyses, which included the majority of patients (58-78%), showed significant reductions in all-cause mortality (trimodulin vs. placebo) in patients with high CRP, low IgM, and high CRP/low IgM at baseline. CONCLUSIONS: No significant differences were found in VFDs and mortality between trimodulin and placebo groups. Post hoc analyses supported improved outcome regarding mortality with trimodulin in subsets of patients with elevated CRP, reduced IgM, or both. These findings warrant further investigation. TRIAL REGISTRATION: NCT01420744.

Multicenter, randomized, placebo-controlled phase III study of pyridoxalated hemoglobin polyoxyethylene in distributive shock (PHOENIX).

OBJECTIVE: To compare the effectiveness and safety of the hemoglobin-based nitric oxide scavenger, pyridoxalated hemoglobin polyoxyethylene, against placebo in patients with vasopressor-dependent distributive shock. DESIGN: Multicenter, randomized, placebo-controlled, open-label study. SETTING: Sixty-one participating ICUs in six European countries (Austria, Belgium, Germany, the Netherlands, Spain, and United Kingdom). PATIENTS: All patients admitted with distributive shock, defined as the presence of at least two systemic inflammatory response syndrome criteria, persisting norepinephrine dependence and evidence of organ dysfunction/hypoperfusion despite adequate fluid resuscitation. INTERVENTIONS: Patients were randomized to receive 0.25 mL/kg/hr pyridoxalated hemoglobin polyoxyethylene (20 mg Hb/kg/hr) or an equal volume of placebo, infused for up to 150 hours, in addition to conventional vasopressor therapy. MEASUREMENTS AND MAIN RESULTS: The study was stopped after interim analysis showed higher mortality in the pyridoxalated hemoglobin polyoxyethylene group and an increased prevalence of adverse events. At this time, 377 patients had been randomized to pyridoxalated hemoglobin polyoxyethylene (n = 183) or placebo (n = 194). Age, gender, type of patient (medical/surgical), and Acute Physiology and Chronic Health Evaluation II scores were similar between groups. Twenty-eight-day mortality rate was 44.3% in the pyridoxalated hemoglobin polyoxyethylene group versus 37.6% in the placebo group (OR, 1.29; 95% CI, 0.85-1.95; p = 0.227). In patients with higher organ dysfunction scores (Sepsis-related Organ Failure Assessment > 13), mortality rates were significantly higher in the pyridoxalated hemoglobin polyoxyethylene group when compared with those in placebo-treated patients (60.9% vs 39.2%; p = 0.014). Survivors who received pyridoxalated hemoglobin polyoxyethylene had a longer vasopressor-free time (21.3 vs 19.7 d; p = 0.035). CONCLUSIONS: In this randomized, controlled phase III trial in patients with vasopressor-dependent distributive shock, administration of a pyridoxalated hemoglobin solution decreased the need for vasopressors but was associated with a trend to increased mortality.

Fluid balance in sepsis and septic shock as a determining factor of mortality.

OBJECTIVE: The objective was to assess whether fluid balance had a determinant impact on mortality rate in a cohort of critically ill patients with severe sepsis or septic shock. DESIGN: A prospective and observational study was carried out on an inception cohort. SETTING: The setting was an intensive care unit of a university hospital. PATIENTS: Patients admitted consecutively in the intensive care unit who were diagnosed with severe sepsis or septic shock were included. INTERVENTIONS: Demographic, laboratory, and clinical data were registered, as well as time of septic shock onset, illness severity (Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment), and comorbidities. Daily and accumulated fluid balance was registered at 24, 48, 72, and 96 hours. Survival curves representing 28-day mortality were built according to the Kaplan-Meier method. RESULTS: A total of 42 patients were included in the analysis: men, 64.3%; mean age, 61.8±15.9 years. Septic shock was predominant in 69% of the cases. Positive blood cultures were obtained in 17 patients (40.5%). No age, sex, Sepsis-related Organ Failure Assessment, creatinine, lactate, venous saturation of O2, and troponin differences were observed upon admission between survivors and nonsurvivors. However, higher Simplified Acute Physiology Score II was observed in nonsurvivors, P=.016. Nonsurvivors also showed higher accumulated positive fluid balance at 48, 72, and 96 hours with statistically significant differences. Besides, significant differences (P=.02) were observed in the survival curve with the risk of mortality at 72 hours between patients with greater than 2.5 L and less than 2.5 L of accumulated fluid balance. CONCLUSIONS: Fluid administration at the onset of severe sepsis or septic shock is the first line of hemodynamic treatment. However, the accumulated positive fluid balance in the first 48, 72, and 96 hours is associated with higher mortality in these critically ill patients.

Successful empirical erlotinib treatment of a mechanically ventilated patient newly diagnosed with metastatic lung adenocarcinoma.

BACKGROUND: Lung cancer is the most common solid tumor in critically ill cancer patients who are admitted to intensive care units (ICUs). An ICU trial consists of unlimited ICU support for a limited time period. CASE REPORT: We present the case of a 60-year-old woman with newly diagnosed metastatic lung adenocarcinoma who required mechanical ventilation due to respiratory failure. Empirical erlotinib treatment was administered through a nasogastric feeding tube as part of an ICU trial, which led to a dramatic and durable response. CONCLUSION: Empirical erlotinib should be considered when epidermal growth factor receptor (EGFR) mutations are suspected in ICU newly diagnosed patients with lung adenocarcinoma.

Real-time continuous glucose monitoring in an intensive care unit: better accuracy in patients with septic shock.

OBJECTIVE: This study assessed the accuracy of real-time continuous glucose monitoring system (RTCGMS) devices in an intensive care unit (ICU) to determine whether the septic status of the patient has any influence on the accuracy of the RTCGMS. SUBJECTS AND METHODS: In total, 41 patients on insulin therapy were included. Patients were monitored for 72 h using RTCGMS. Arterial blood glucose (ABG) samples were obtained following the protocol established in the ICU. The results were evaluated using paired values (excluding those used for calibration) with the performance assessed using numerical accuracy. Nonparametric tests were used to determine statistically significant differences in accuracy. RESULTS: In total, 956 ABG/RTCGMS pairs were analyzed. The overall median relative absolute difference (RAD) was 13.5%, and the International Organization for Standardization (ISO) criteria were 68.1%. The median RADs reported for patients with septic shock, with sepsis, and without sepsis were 11.2%, 14.3%, and 16.3%, respectively (P<0.05). Measurements meeting the ISO criteria were 74.5%, 65.6%, and 63.7% for patients with septic shock, with sepsis, and without sepsis, respectively (P<0.05). CONCLUSIONS: The results showed that the septic status of patients influenced the accuracy of the RTCGMS in the ICU. Accuracy was significantly better in patients with septic shock in comparison with the other patient cohorts.

Linezolid more efficacious than vancomycin to eradicate infecting organism in critically ill patients with Gram-positive infections.

OBJECTIVE: A prospective and observational study has been conducted to analyze the efficacious of linezolid compared to vancomycin to eradicate the infecting organism in critically ill patients with Gram-positive infections. PATIENTS AND METHODS: Prospective, observational and non-controlled study in a medical-surgical intensive care unit (ICU) in a university hospital. A total number of 53 critically ill patients with therapy to proven Gram-positive bacterial infection were studied. Infected patients were diagnosed and treated according to international guidelines, following standard protocol for the critically ill infected patients. Microbiologic eradication of the infecting organism at the seventh day of treatment and patients' clinical outcome were analysed. RESULTS: Twenty-seventh patients received linezolid and twenty-six received vancomycin. Infection-site diagnoses were: hospital-acquired pneumonia (21 cases: 39.6%), complicated surgical-site infection (19 cases: 35.8%) and catheter-related bacteraemia (13 cases: 24.5%). The most important isolated microorganism was methicillin-resistant Staphylococcus aureus (MRSA) (28 cases: 52.8%). Clinical success was 20/ 27 (74.1%) in the linezolid group and 16/ 26 (61.5 %) in the vancomycin group, with p = 0.3. The adjusted logistic regression model demonstrated that the treatment with linezolid is associated to microbiologic eradication of the infecting organism at the seventh day of treatment [OR = 7.88 (95% CI 1.86-33.52)] and p = 0.005. In this model, the length of hospital stay was lower in the group with microbiologic eradication at the seventh day (p = 0.015). Drug-related adverse events were comparable in both groups of treatment. CONCLUSION: Treatment with linezolid in critically ill patients with Gram-positive infections was equivalent to vancomycin in terms of efficacy and safety, but linezolid was associated to a higher rate of microbiologic eradication of the infecting organism at the seventh day of treatment.

Effectiveness of treatments for severe sepsis: a prospective, multicenter, observational study.

RATIONALE: Several Surviving Sepsis Campaign Guidelines recommendations are reevaluated. OBJECTIVES: To analyze the effectiveness of treatments recommended in the sepsis guidelines. METHODS: In a prospective observational study, we studied all adult patients with severe sepsis from 77 intensive care units. We recorded compliance with four therapeutic goals (central venous pressure 8 mm Hg or greater for persistent hypotension despite fluid resuscitation and/or lactate greater than 36 mg/dl, central venous oxygen saturation 70% or greater for persistent hypotension despite fluid resuscitation and/or lactate greater than 36 mg/dl, blood glucose greater than or equal to the lower limit of normal but less than 150 mg/dl, and inspiratory plateau pressure less than 30 cm H(2)O for mechanically ventilated patients) and four treatments (early broad-spectrum antibiotics, fluid challenge in the event of hypotension and/or lactate greater than 36 mg/dl, low-dose steroids for septic shock, drotrecogin alfa [activated] for multiorgan failure). The primary outcome measure was hospital mortality. The effectiveness of each treatment was estimated using propensity scores. MEASUREMENTS AND MAIN RESULTS: Of 2,796 patients, 41.6% died before hospital discharge. Treatments associated with lower hospital mortality were early broad-spectrum antibiotic treatment (treatment within 1 hour vs. no treatment within first 6 hours of diagnosis; odds ratio, 0.67; 95% confidence interval, 0.50-0.90; P = 0.008) and drotrecogin alfa (activated) (odds ratio, 0.59; 95% confidence interval, 0.41-0.84; P = 0.004). Fluid challenge and low-dose steroids showed no benefits. CONCLUSIONS: In severe sepsis, early administration of broad-spectrum antibiotics in all patients and administration of drotrecogin alfa (activated) in the most severe patients reduce mortality.

Gastric perforations from abdominal trauma.

BACKGROUND: Gastric rupture due to abdominal trauma is rare (0.02-1.7%); it is usually caused by traffic accidents. Delayed diagnosis, abdominal contamination and associated lesions cause morbidity and mortality. PATIENTS AND METHODS: Retrospective review of 2,083 patients with abdominal traumatism treated at our center over 20 years. We reviewed recent ingestion of a meal, etiology, time to surgery, site, Stomach Injury Scale, abdominal contamination, treatment, associated injuries, complications and mortality. RESULTS: Gastric perforation occurred in 25 patients (1.2%), median age 35 years. Stomachs were distended from recent meals in 16 (64%). The commonest causes were traffic accidents (n = 13) and blunt weapon injury (n = 7). The median time to surgery was 1 h. Gastric lesions occurred predominantly in the anterior wall (n = 12) followed by the greater curvature (n = 7). Type II lesions repaired with simple suturing were the most usual. Abdominal contamination occurred in all cases. Associated lesions were present in 22 patients; the most commonly affected intra-abdominal organ was the liver, and the lungs were the most affected extra-abdominal organ. The morbidity rate was 60% (n = 15) and the mortality rate 4% (n = 1). CONCLUSION: Early diagnosis and surgical treatment are important for reducing the morbidity and mortality in these patients.

Combination antibiotic therapy improves survival in patients with community-acquired pneumonia and shock.

OBJECTIVE: To assess whether combination antibiotic therapy improves outcome of severe community-acquired pneumonia in the subset of patients with shock. DESIGN: Secondary analysis of a prospective observational, cohort study. SETTING: Thirty-three intensive care units (ICUs) in Spain. PATIENTS: Patients were 529 adults with community-acquired pneumonia requiring ICU admission. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Two hundred and seventy (51%) patients required vasoactive drugs and were categorized as having shock. The effects of combination antibiotic therapy and monotherapy on survival were compared using univariate analysis and a Cox regression model. The adjusted 28-day in-ICU mortality was similar (p = .99) for combination antibiotic therapy and monotherapy in the absence of shock. However, in patients with shock, combination antibiotic therapy was associated with significantly higher adjusted 28-day in-ICU survival (hazard ratio, 1.69; 95% confidence interval, 1.09-2.60; p = .01) in a Cox hazard regression model. Even when monotherapy was appropriate, it achieved a lower 28-day in-ICU survival than an adequate antibiotic combination (hazard ratio, 1.64; 95% confidence interval, 1.01-2.64). CONCLUSIONS: Combination antibiotic therapy does not seem to increase ICU survival in all patients with severe community-acquired pneumonia. However, in the subset of patients with shock, combination antibiotic therapy improves survival rates.

Colonization of the medial lumen is a risk factor for catheter-related bloodstream infection.

OBJECTIVE: To analyze the colonization of each lumen and the risk factors for triple-lumen central venous catheter-related bloodstream infection (CRBI). DESIGN AND SETTING: Prospective, observational study in the medical-surgical intensive care unit (ICU) of a teaching hospital. PATIENTS: A total of 120 patients requiring the insertion of a triple-lumen catheter. INTERVENTIONS: Cultures of the catheter. MEASUREMENTS AND RESULTS: The catheters were removed when CRBI was suspected or at discharge from ICU. At the removal time, blood cultures, a swab of the insertion site and a culture of the catheter tip were performed. Furthermore, we made quantitative cultures of the proximal, medial and distal lumen. We diagnosed CRBI in six patients (3.35 CRBI/1,000 days at risk), and we observed that in these patients colonization of the medial lumen was more frequent (5/6) than in patients without CRBI (9/114; p = 0.0001). The logistic regression analysis showed that colonization of the medial lumen was an independent risk factor for CRBI (OR 28.1, 95% CI 2.2-364.9). CONCLUSIONS: Colonization of the medial lumen is an independent risk factor for triple-lumen catheter-related bloodstream infection, possibly due to the absence of use of this lumen.

[Randomized, prospective and comparative clinical trial of piperacillin/tazobactam versus ceftriaxone plus ornidazole in the treatment of biliary tract infections]. / Estudio comparativo, prospectivo y aleatorizado de piperacilina/tazobactam frente a ceftriaxona y ornidazol en el tratamiento de las infecciones de las vías biliares.

BACKGROUND AND OBJECTIVE: The treatment of biliary tract infections requires antibiotics and an appropriate surgical procedure. The aim of this study was to evaluate the efficacy and safety of piperacillin/tazobactam versus ceftriaxone plus ornidazole in the treatment of biliary tract infections. PATIENTS AND METHOD: This was a randomized, prospective and comparative clinical trial of two antibiotic regimens in the treatment of biliary tract infection. One hundred and fifty three patients were randomly allocated into two groups; three patients were excluded after randomization. One group (n = 75) received piperacillin/tazobactam (4 g/8 h iv) and the other group (n = 75) was administered a combination of ceftriaxone (2 g/24 h iv) plus ornidazole (1 g/24 h iv). In both groups, protocolized surgical or endoscopic procedures were carried out. Clinical efficacy and safety were assessed at the end of treatment. RESULTS: Demographic data and severity of disease were similar in both groups. Three patients were excluded of the study by deviations from the protocol. Sixty-seven patients (89.3%) out of the piperacillin/tazobactam group and sixty-six patients (88%) out of the ceftriaxone plus ornidazole group were clinically cured (OR = 0.87 [95% CI, 0.31-2.4]). Twelve patients died, seven in the piperacillin/tazobactam group and five in the ceftriaxone plus ornidazole group. Adverse events were similar in both groups (OR = 1.18 [95% CI, 0.37-3.7]). CONCLUSIONS: This study suggests that piperacillin/tazobactam is as efficacious and safe as ceftriaxone plus ornidazole in the treatment of biliary tract infections.

Antibiotic prophylaxis strategies in the prevention of ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) is defined as a nosocomial pneumonia occurring > 48 h after endotracheal intubation. VAP may occur very early after intubation and it is usually defined as early-onset pneumonia, which occurs during the first 4 days. The occurrence of VAP is associated with an increase in morbidity and mortality. The pathogenesis of VAP often results from aspiration of colonised secretions in injured patients and this colonisation of the upper airway acts as a main risk factor in the development of pneumonia. It has been hypothesised that the bacterial inoculum may be decreased through the administration of systemic antibiotic prophylaxis. Antibiotic prophylaxis strategies to prevent VAP can be administered over an extended period to cover all microorganisms using selective digestive decontamination regimens, or in a short-term course of no more than 24 h. Probably, the second strategy is the most useful in the prevention of VAP because it has a lower impact on the emergence of bacterial resistance. This manuscript aims to review current opinions regarding antibiotic prophylaxis strategies in the prevention of VAP.

Microscopic examination of intracellular organisms in protected bronchoalveolar mini-lavage fluid for the diagnosis of ventilator-associated pneumonia.

STUDY OBJECTIVES: To assess the cutoff percentage of cells containing intracellular organisms (ICOs) in the microscopic examination of mini-lavage fluid for the diagnosis of ventilator-associated pneumonia (VAP), and to study the accuracy of this diagnostic procedure on patients who have received previous antibiotic therapy (AT). DESIGN: Prospective clinical investigation. SETTING: The medico-surgical ICU of a university hospital. PATIENTS: Eighty-two patients who fulfilled the clinical criteria of first episode of VAP. INTERVENTIONS: Lower airway secretion samples were obtained by a nonbronchoscopic protected bronchoalveolar mini-lavage (mini-PBAL). MEASUREMENTS AND RESULTS: A total of 82 mini-PBALs were performed. The fluid obtained was divided into two samples. The first sample underwent direct microscopic examination using centrifugal cytology and Giemsa stain in order to determine the percentage of cells containing ICOs. The second sample was processed for Gram stain and quantitative cultures. VAP was the final diagnosis in 65 patients based on the mini-PBAL results obtained in the quantitative cultures. At least one bacterial species grew in a significant concentration (> or = 10(3) cfu/mL). The mini-PBAL was performed on 42 patients during AT (> or = 24 h of effective AT at the time of diagnostic procedure) and on another 40 patients with no AT (No AT). The results of the quantitative cultures were compared with the percentage of cells containing ICOs using a receiver operator characteristic (ROC) curve. The cutoff point of > or = 2% of cells containing ICOs had the highest sensitivity (80%) and specificity (82%) in the studied population (area under the ROC curve [AUC], 0.83; 95% confidence interval [CI], 0.70 to 0.90). In patients receiving AT, the sensitivity was 70% and specificity was 75% (AUC, 0.73; 95% CI, 0.58 to 0.90); and in No AT-group patients sensitivity was 88% and specificity was 100% (AUC, 0.92; 95% CI, 0.84 to 1.0). The comparative analysis of both ROC curves was statistically significant (p = 0.04). CONCLUSIONS: The cutoff point of > or = 2% of cells containing ICOs has the highest sensitivity and specificity in the microscopic examination of mini-lavage fluid for the diagnosis of VAP. However, sensitivity is too low to be clinically useful. The direct examination of mini-PBAL fluid is less accurate when previous AT has been administered.