Attributable mortality due to nosocomial sepsis in Brazilian hospitals: a case-control study.

BACKGROUND: Nosocomial sepsis is a major healthcare issue, but there are few data on estimates of its attributable mortality. We aimed to estimate attributable mortality fraction (AF) due to nosocomial sepsis. METHODS: Matched 1:1 case-control study in 37 hospitals in Brazil. Hospitalized patients in participating hospitals were included. Cases were hospital non-survivors and controls were hospital survivors, which were matched by admission type and date of discharge. Exposure was defined as occurrence of nosocomial sepsis, defined as antibiotic prescription plus presence of organ dysfunction attributed to sepsis without an alternative reason for organ failure; alternative definitions were explored. Main outcome measurement was nosocomial sepsis-attributable fractions, estimated using inversed-weight probabilities methods using generalized mixed model considering time-dependency of sepsis occurrence. RESULTS: 3588 patients from 37 hospitals were included. Mean age was 63 years and 48.8% were female at birth. 470 sepsis episodes occurred in 388 patients (311 in cases and 77 in control group), with pneumonia being the most common source of infection (44.3%). Average AF for sepsis mortality was 0.076 (95% CI 0.068-0.084) for medical admissions; 0.043 (95% CI 0.032-0.055) for elective surgical admissions; and 0.036 (95% CI 0.017-0.055) for emergency surgeries. In a time-dependent analysis, AF for sepsis rose linearly for medical admissions, reaching close to 0.12 on day 28; AF plateaued earlier for other admission types (0.04 for elective surgery and 0.07 for urgent surgery). Alternative sepsis definitions yield different estimates. CONCLUSION: The impact of nosocomial sepsis on outcome is more pronounced in medical admissions and tends to increase over time. The results, however, are sensitive to sepsis definitions.

Twelve Months and Counting: Following Clinical Outcomes in Critical COVID-19 Survivors.

Rationale: Recent reports suggest that patients with severe coronavirus disease (COVID-19) often experience long-term consequences of the infection. However, studies on intensive care unit (ICU) survivors are underrepresented. Objectives: We aimed to explore 12-month clinical outcomes after critical COVID-19, describing the longitudinal progress of disabilities, frailty status, frequency of cognitive impairment, and clinical events (rehospitalization, institutionalization, and falls). Methods: We performed a prospective cohort study of survivors of COVID-19 ICU admissions in Sao Paulo, Brazil. We assessed patients every 3 months for 1 year after hospital discharge and obtained information on 15 activities of daily living (basic, instrumental, and mobility activities), frailty, cognition, and clinical events. Results: We included 428 patients (mean age of 64 yr, 61% required invasive mechanical ventilation during ICU stay). The number of disabilities peaked at 3 months compared with the pre-COVID-19 period (mean difference, 2.46; 99% confidence interval, 1.94-2.99) and then decreased at 12 months (mean difference, 0.67; 99% confidence interval, 0.28-1.07). At 12-month follow-up, 12% of patients were frail, but half of them presented frailty only after COVID-19. The prevalence of cognitive symptoms was 17% at 3 months and progressively decreased to 12.1% (P = 0.012 for trend) at the end of 1 year. Clinical events occurred in all assessments. Conclusions: Although a higher burden of disabilities and cognitive symptoms occurred 3 months after hospital discharge of critical COVID-19 survivors, a significant improvement occurred during the 1-year follow-up. However, one-third of the patients remained in worse conditions than their pre-COVID-19 status.

Phrenic Nerve Block and Respiratory Effort in Pigs and Critically Ill Patients with Acute Lung Injury.

BACKGROUND: Strong spontaneous inspiratory efforts can be difficult to control and prohibit protective mechanical ventilation. Instead of using deep sedation and neuromuscular blockade, the authors hypothesized that perineural administration of lidocaine around the phrenic nerve would reduce tidal volume (VT) and peak transpulmonary pressure in spontaneously breathing patients with acute respiratory distress syndrome. METHODS: An established animal model of acute respiratory distress syndrome with six female pigs was used in a proof-of-concept study. The authors then evaluated this technique in nine mechanically ventilated patients under pressure support exhibiting driving pressure greater than 15 cm H2O or VT greater than 10 ml/kg of predicted body weight. Esophageal and transpulmonary pressures, electrical activity of the diaphragm, and electrical impedance tomography were measured in pigs and patients. Ultrasound imaging and a nerve stimulator were used to identify the phrenic nerve, and perineural lidocaine was administered sequentially around the left and right phrenic nerves. RESULTS: Results are presented as median [interquartile range, 25th to 75th percentiles]. In pigs, VT decreased from 7.4 ml/kg [7.2 to 8.4] to 5.9 ml/kg [5.5 to 6.6] (P < 0.001), as did peak transpulmonary pressure (25.8 cm H2O [20.2 to 27.2] to 17.7 cm H2O [13.8 to 18.8]; P < 0.001) and driving pressure (28.7 cm H2O [20.4 to 30.8] to 19.4 cm H2O [15.2 to 22.9]; P < 0.001). Ventilation in the most dependent part decreased from 29.3% [26.4 to 29.5] to 20.1% [15.3 to 20.8] (P < 0.001). In patients, VT decreased (8.2 ml/ kg [7.9 to 11.1] to 6.0 ml/ kg [5.7 to 6.7]; P < 0.001), as did driving pressure (24.7 cm H2O [20.4 to 34.5] to 18.4 cm H2O [16.8 to 20.7]; P < 0.001). Esophageal pressure, peak transpulmonary pressure, and electrical activity of the diaphragm also decreased. Dependent ventilation only slightly decreased from 11.5% [8.5 to 12.6] to 7.9% [5.3 to 8.6] (P = 0.005). Respiratory rate did not vary. Variables recovered 1 to 12.7 h [6.7 to 13.7] after phrenic nerve block. CONCLUSIONS: Phrenic nerve block is feasible, lasts around 12 h, and reduces VT and driving pressure without changing respiratory rate in patients under assisted ventilation.

Trends in clinical profiles, organ support use and outcomes of patients with cancer requiring unplanned ICU admission: a multicenter cohort study.

PURPOSE: To describe trends in outcomes of cancer patients with unplanned admissions to intensive-care units (ICU) according to cancer type, organ support use, and performance status (PS) over an 8-year period. METHODS: We retrospectively analyzed prospectively collected data from all cancer patients admitted to 92 medical-surgical ICUs from July/2011 to June/2019. We assessed trends in mortality through a Bayesian hierarchical model adjusted for relevant clinical confounders and whether there was a reduction in ICU length-of-stay (LOS) over time using a competing risk model. RESULTS: 32,096 patients (8.7% of all ICU admissions; solid tumors, 90%; hematological malignancies, 10%) were studied. Bed/days use by cancer patients increased up to more than 30% during the period. Overall adjusted mortality decreased by 9.2% [95% credible interval (CI), 13.1-5.6%]. The largest reductions in mortality occurred in patients without need for organ support (9.6%) and in those with need for mechanical ventilation (MV) only (11%). Smallest reductions occurred in patients requiring MV, vasopressors, and dialysis (3.9%) simultaneously. Survival gains over time decreased as PS worsened. Lung cancer patients had the lowest decrease in mortality. Each year was associated with a lower sub-hazard for ICU death [SHR 0.93 (0.91-0.94)] and a higher chance of being discharged alive from the ICU earlier [SHR 1.01 (1-1.01)]. CONCLUSION: Outcomes in critically ill cancer patients improved in the past 8 years, with reductions in both mortality and ICU LOS, suggesting improvements in overall care. However, outcomes remained poor in patients with lung cancer, requiring multiple organ support and compromised PS.

Characteristics and outcomes of patients with COVID-19 admitted to the ICU in a university hospital in São Paulo, Brazil - study protocol.

OBJECTIVES: We designed a cohort study to describe characteristics and outcomes of patients with coronavirus disease (COVID-19) admitted to the intensive care unit (ICU) in the largest public hospital in Sao Paulo, Brazil, as Latin America becomes the epicenter of the pandemic. METHODS: This is the protocol for a study being conducted at an academic hospital in Brazil with 300 adult ICU beds dedicated to COVID-19 patients. We will include adult patients admitted to the ICU with suspected or confirmed COVID-19 during the study period. The main outcome is ICU survival at 28 days. Data will be collected prospectively and retrospectively by trained investigators from the hospital's electronic medical records, using an electronic data capture tool. We will collect data on demographics, comorbidities, severity of disease, and laboratorial test results at admission. Information on the need for advanced life support and ventilator parameters will be collected during ICU stay. Patients will be followed up for 28 days in the ICU and 60 days in the hospital. We will plot Kaplan-Meier curves to estimate ICU and hospital survival and perform survival analysis using the Cox proportional hazards model to identify the main risk factors for mortality. ClinicalTrials.gov: NCT04378582. RESULTS: We expect to include a large sample of patients with COVID-19 admitted to the ICU and to be able to provide data on admission characteristics, use of advanced life support, ICU survival at 28 days, and hospital survival at 60 days. CONCLUSIONS: This study will provide epidemiological data about critically ill patients with COVID-19 in Brazil, which could inform health policy and resource allocation in low- and middle-income countries.

Characteristics and outcomes of patients with COVID-19 admitted to the ICU in a university hospital in São Paulo, Brazil - study protocol

OBJECTIVES: We designed a cohort study to describe characteristics and outcomes of patients with coronavirus disease (COVID-19) admitted to the intensive care unit (ICU) in the largest public hospital in Sao Paulo, Brazil, as Latin America becomes the epicenter of the pandemic. METHODS: This is the protocol for a study being conducted at an academic hospital in Brazil with 300 adult ICU beds dedicated to COVID-19 patients. We will include adult patients admitted to the ICU with suspected or confirmed COVID-19 during the study period. The main outcome is ICU survival at 28 days. Data will be collected prospectively and retrospectively by trained investigators from the hospital's electronic medical records, using an electronic data capture tool. We will collect data on demographics, comorbidities, severity of disease, and laboratorial test results at admission. Information on the need for advanced life support and ventilator parameters will be collected during ICU stay. Patients will be followed up for 28 days in the ICU and 60 days in the hospital. We will plot Kaplan-Meier curves to estimate ICU and hospital survival and perform survival analysis using the Cox proportional hazards model to identify the main risk factors for mortality. ClinicalTrials.gov: NCT04378582. RESULTS: We expect to include a large sample of patients with COVID-19 admitted to the ICU and to be able to provide data on admission characteristics, use of advanced life support, ICU survival at 28 days, and hospital survival at 60 days. CONCLUSIONS: This study will provide epidemiological data about critically ill patients with COVID-19 in Brazil, which could inform health policy and resource allocation in low- and middle-income countries.

Heterogeneous effects of alveolar recruitment in acute respiratory distress syndrome: a machine learning reanalysis of the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial.

BACKGROUND: Despite a robust physiological rationale, recruitment manoeuvres with PEEP titration were associated with harm in the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). We sought to investigate the potential heterogeneity in treatment effects in patients enrolled in the ART, using a machine learning approach. METHODS: The primary outcome was hospital mortality. Patients were clustered using baseline clinical and physiological data using the k-means for mixed large data method. The heterogeneity in treatment effect between clusters was investigated using Bayesian methods. We further investigated whether baseline driving pressure could modulate the association between treatment arm, cluster, and mortality. RESULTS: Data from all 1010 patients enrolled in the ART were analysed. Partitioning suggested that three clusters were present in the ART population. The largest cluster (Cluster 1) was characterised by patients with pneumonia and requiring vasopressor support. Recruitment manoeuvres with PEEP titration were associated with higher mortality in Cluster 1 (probability of harm of >98%), but this association was absent in Clusters 2 and 3 (probability of harm of 45% and 68%, respectively). Higher baseline driving pressure was associated with a progressive reduction in the association between alveolar recruitment with PEEP titration and mortality. CONCLUSIONS: Recruitment manoeuvre with PEEP titration may be harmful in acute respiratory distress syndrome (ARDS) patients with pneumonia or requiring vasopressor support. Driving pressure appears to modulate the association between the ART study intervention, aetiology of ARDS, and mortality. This machine learning approach may help tailor future RCTs. CLINICAL TRIAL REGISTRATION: NCT01374022.

Factors associated with renal Doppler resistive index in critically ill patients: a prospective cohort study.

BACKGROUND: The renal Doppler resistive index (renal RI) is a noninvasive tool that has been used to assess renal perfusion in the intensive care unit (ICU) setting. However, many parameters have been described as influential on the values of renal RI. Therefore, we proposed this study to evaluate the variables that could impact renal RI in critically ill patients. METHODS: A prospective observational study was performed in a 14-bed medical-surgical adult ICU. All consecutive patients admitted to the ICU during the study period were evaluated for eligibility. Renal RI was performed daily until the third day after ICU admission, death, or renal replacement therapy (RRT) requirement. Clinical and blood test data were collected throughout this period. Acute kidney injury (AKI) reversibility was categorized as transient (normalization of renal function within 3 days of AKI onset) or persistent (non-resolution of AKI within 3 days of onset or need for RRT). A linear mixed model was applied to evaluate the factors that could influence renal RI. RESULTS: Eighty-three consecutive patients were included. Of these, 65% were male and 50.6% were medical admissions. Mean SAPS 3 was 47 ± 16. Renal RI was significantly different between no-AKI (0.64 ± 0.06), transient AKI (0.64 ± 0.07), and persistent AKI groups (0.70 ± 0.08, p < 0.01). Variables associated with renal RI variations were mean arterial pressure, lactate, age, and persistent AKI (p < 0.05). No association between serum chloride and renal RI was observed (p = 0.868). CONCLUSIONS: Mean arterial pressure, lactate, age, and type of AKI might influence renal RI in critically ill patients.

Improving serum calcium test ordering according to a decision algorithm.

AIM: To detect differences in the pattern of serum calcium tests ordering before and after the implementation of a decision algorithm. METHODS: We studied patients admitted to an internal medicine ward of a university hospital on April 2013 and April 2016. Patients were classified as critical or non-critical on the day when each test was performed. Adequacy of ordering was defined according to adherence to a decision algorithm implemented in 2014. RESULTS: Total and ionised calcium tests per patient-day of hospitalisation significantly decreased after the algorithm implementation; and duplication of tests (total and ionised calcium measured in the same blood sample) was reduced by 49%. Overall adequacy of ionised calcium determinations increased by 23% (P=0.0001) due to the increase in the adequacy of ionised calcium ordering in non-critical conditions. CONCLUSIONS: A decision algorithm can be a useful educational tool to improve adequacy of the process of ordering serum calcium tests.

Association of frailty with short-term outcomes, organ support and resource use in critically ill patients.

PURPOSE: Frail patients are known to experience poor outcomes. Nevertheless, we know less about how frailty manifests itself in patients' physiology during critical illness and how it affects resource use in intensive care units (ICU). We aimed to assess the association of frailty with short-term outcomes and organ support used by critically ill patients. METHODS: Retrospective analysis of prospective collected data from 93 ICUs in Brazil from 2014 to 2015. We assessed frailty using the modified frailty index (MFI). The primary outcome was in-hospital mortality. Secondary outcomes were discharge home without need for nursing care, ICU and hospital length of stay (LOS), and utilization of ICU organ support and transfusion. We used mixed logistic regression and competing risk models accounting for relevant confounders in outcome analyses. RESULTS: The analysis consisted of 129,680 eligible patients. There were 40,779 (31.4%) non-frail (MFI = 0), 64,407 (49.7%) pre-frail (MFI = 1-2) and 24,494 (18.9%) frail (MFI ≥ 3) patients. After adjusted analysis, frailty was associated with higher in-hospital mortality (OR 2.42, 95% CI 1.89-3.08), particularly in patients admitted with lower SOFA scores. Frail patients were less likely to be discharged home (OR 0.36, 95% CI 0.54-0.79) and had higher hospital and ICU LOS than non-frail patients. Use of all forms of organ support (mechanical ventilation, non-invasive ventilation, vasopressors, dialysis and transfusions) were more common in frail patients and increased as MFI increased. CONCLUSIONS: Frailty, as assessed by MFI, was associated with several patient-centered endpoints including not only survival, but also ICU LOS and organ support.

Laboratory Tests Ordering Pattern by Medical Residents From a Brazilian University Hospital.

OBJECTIVES: The adequacy of laboratory test orders by medical residents is a longstanding issue. The aim of this study is to analyze the number, types, and pattern of repetition of tests ordered by medical residents. METHODS: We studied all tests ordered over a 1-year period for inpatients of an internal medicine ward in a university hospital. Types, results, and repetition pattern of tests were analyzed in relation to patients' diagnoses. RESULTS: We evaluated 117,666 tests, requested for 1,024 inpatients. The mean number of tests was 9.5 per day. The test repetition pattern was similar, regardless of patients' diagnoses, previous test results, or duration of stay. The probability of an abnormal result after a sequence of three normal tests was lower than 25%, regardless of the diagnosis. CONCLUSIONS: Number of tests and repetition were both high, imposing costs, discomfort, and risks to patients, thus warranting further investigation.

Prevalence of Ventilatory Conditions for Dynamic Fluid Responsiveness Prediction in 2 Tertiary Intensive Care Units.

BACKGROUND: Dynamic parameters for fluid responsiveness obtained from heart-lung interaction during invasive mechanical ventilation require specific conditions not always present in intensive care unit (ICU) patients. The aim of this study was to examine the prevalence of these conditions in critically ill patients. METHODS: We conducted a prospective observational study in 2 medical-surgical ICUs. We evaluated whether it would be possible to measure dynamic indices of fluid responsiveness when fluid expansion was administered. We recorded whether the patients were in controlled invasive mechanical ventilation with tidal volume >8 mL/kg and without arrhythmias. The proportion of patients who fulfilled these conditions was recorded. A post hoc subgroup analyses by terciles of Simplified Acute Physiology Score 3 (SAPS3) were performed. RESULTS: A total of 826 fluid challenges were undertaken in 424 patients during the study. The use of controlled mechanical ventilation with tidal volume > 8 mL/kg and without arrhythmias occurred in only 2.9% of the patients at the time of fluid challenge episodes. There was an increase in the prevalence of these conditions as the severity of the patients also increased: lower tercile of SAPS3 (0%), intermediate tercile (2%), and higher tercile (6.9%; P < .01 Pearson chi-square test). CONCLUSIONS: Respiratory-dependent dynamic parameters for predicting fluid responsiveness in ICU may have restricted applicability in daily practice, even in more severe patients, due to low prevalence of required conditions.

Nebulized antibiotics for ventilator-associated pneumonia: a systematic review and meta-analysis.

INTRODUCTION: Nebulized antibiotics are a promising new treatment option for ventilator-associated pneumonia. However, more evidence of the benefit of this therapy is required. METHODS: The Medline, Scopus, EMBASE, Biological Abstracts, CAB Abstracts, Food Science and Technology Abstracts, CENTRAL, Scielo and Lilacs databases were searched to identify randomized controlled trials or matched observational studies that compared nebulized antibiotics with or without intravenous antibiotics to intravenous antibiotics alone for ventilator-associated pneumonia treatment. Two reviewers independently collected data and assessed outcomes and risk of bias. The primary outcome was clinical cure. Secondary outcomes were microbiological cure, ICU and hospital mortality, duration of mechanical ventilation, ICU length of stay and adverse events. A mixed-effect model meta-analysis was performed. Trial sequential analysis was used for the main outcome of interest. RESULTS: Twelve studies were analyzed, including six randomized controlled trials. For the main outcome analysis, 812 patients were included. Nebulized antibiotics were associated with higher rates of clinical cure (risk ratio (RR) = 1.23; 95% confidence interval (CI), 1.05 to 1.43; I(2) = 34%; D(2) = 45%). Nebulized antibiotics were not associated with microbiological cure (RR = 1.24; 95% CI, 0.95 to 1.62; I(2) = 62.5), mortality (RR = 0.90; CI 95%, 0.76 to 1.08; I(2) = 0%), duration of mechanical ventilation (standardized mean difference = -0.10 days; 95% CI, -1.22 to 1.00; I(2) = 96.5%), ICU length of stay (standardized mean difference = 0.14 days; 95% CI, -0.46 to 0.73; I(2) = 89.2%) or renal toxicity (RR = 1.05; 95% CI, 0.70 to 1.57; I(2) = 15.6%). Regarding the primary outcome, the number of patients included was below the information size required for a definitive conclusion by trial sequential analysis; therefore, our results regarding this parameter are inconclusive. CONCLUSIONS: Nebulized antibiotics seem to be associated with higher rates of clinical cure in the treatment of ventilator-associated pneumonia. However, the apparent benefit in the clinical cure rate observed by traditional meta-analysis does not persist after trial sequential analysis. Additional high-quality studies on this subject are highly warranted. TRIAL REGISTRATION NUMBER: CRD42014009116 . Registered 29 March 2014.

Sepsis-related deaths in Brazil: an analysis of the national mortality registry from 2002 to 2010.

INTRODUCTION: Limited population-based epidemiologic information about sepsis' demography, including its mortality and temporal changes is available from developing countries. We investigated the epidemiology of sepsis deaths in Brazil using secondary data from the Brazilian Mortality Information System. METHODS: Retrospective descriptive analysis of Brazilian multiple-cause-of-death data between 2002 and 2010, with sepsis-associated International Classification of Diseases, 10th Revision (ICD-10) code indicated as the cause of death. Population-based sepsis associated mortality rates and trends were estimated. Annual population-based mortality rates were calculated using age-stratified population estimates from the 2010 census provided by the Brazilian Institute of Geography and Statistics as denominators. RESULTS: The total number of annual deaths recorded in Brazil increased over the decade, from 982,294 deaths reported in 2002 to 1,133,761 deaths reported in 2010. The number of sepsis associated deaths also increased both in absolute numbers and proportions from 95,972 (9.77% of total deaths) in 2002 to 186,712 deaths (16.46%) in 2010. The age-adjusted rate of sepsis-associated mortality increased from 69.5 deaths per 100,000 to 97.8 deaths per 100,000 population from 2002 to 2010 (P < 0.001). Sepsis-associated mortality was higher in individuals older than 60 years of age as compared to subjects aged 0 to 20 years (adjusted rate ratio 15.7 (95% confidence interval (CI) 15.6 to 15.8)) and in male subjects (1.15 (95% CI 1.15 to 1.16)). CONCLUSIONS: Between 2002 and 2010 the contribution of sepsis to all cause mortality as reported in multiple-cause-of-death forms increased significantly in Brazil. Age-adjusted mortality rates by sepsis also increased in the last decade. Our results confirm the importance of sepsis as a significant healthcare issue in Brazil.

Complete motor recovery after acute paraparesis caused by spontaneous spinal epidural hematoma: case report.

BACKGROUND: Spontaneous spinal epidural hematoma is a relatively rare but potentially disabling disease. Prompt timely surgical management may promote recovery even in severe cases. CASE PRESENTATION: We report a 34-year-old man with a 2-hour history of sudden severe back pain, followed by weakness and numbness over the bilateral lower limbs, progressing to intense paraparesis and anesthesia. A spinal magnetic resonance imaging scan was performed and revealed an anterior epidural hematoma of the thoracic spine. He underwent an emergency decompression laminectomy of the thoracic spine and hematoma evacuation. Just after surgery, his lower extremity movements improved. After 1 week, there was no residual weakness and ambulation without assistance was resumed, with residual paresthesia on the plantar face of both feet. After 5 months, no residual symptoms persisted. CONCLUSIONS: The diagnosis of spontaneous spinal epidural hematoma must be kept in mind in cases of sudden back pain with symptoms of spinal cord compression. Early recognition, accurate diagnosis and prompt surgical treatment may result in significant improvement even in severe cases.