Association between piperacillin/tazobactam use and acute kidney injury in critically ill patients: a retrospective multicentre cohort study.

BACKGROUND: Piperacillin/tazobactam is one of the most common antibiotics prescribed in the ICU and the combination of piperacillin/tazobactam with vancomycin has been associated with acute kidney injury (AKI) in critically ill patients. However, data on the risk of AKI with piperacillin/tazobactam, despite vancomycin co-exposure, are lacking. OBJECTIVES: To investigate the association of piperacillin/tazobactam with AKI and renal replacement therapy (RRT) among adult ICU patients. METHODS: We analysed data from patients included in two open access databases (MIMIC-IV and eICU). Critically ill patients who received piperacillin/tazobactam or cefepime (a cephalosporin with similar broad-spectrum activity to piperacillin/tazobactam) during their first ICU stay were eligible for the study. Marginal structural Cox models, accounting for time-fixed covariates and time-dependent covariates were performed. The primary outcomes were AKI and need of RRT. RESULTS: A total of 20 107 patients were included, with 11 213 in the piperacillin/tazobactam group and 8894 in the cefepime group. Exposure to piperacillin/tazobactam was associated with AKI (HR 1.77; 95% CI 1.51-2.07; P < 0.001) and with need of RRT (HR 1.31; 95% CI 1.08-1.57; P = 0.005). Tests for interaction were not statistically significant for occurrence of AKI and RRT in the subgroup of patients exposed to vancomycin or not (P = 0.26 and P = 0.6, respectively). CONCLUSIONS: In critically ill patients, exposure to piperacillin/tazobactam was associated with increased risk of AKI and with increased risk of RRT, regardless of combination therapy with vancomycin.

Early Versus Late Initiation of Renal Replacement Therapy in Critically Ill Patients: Systematic Review and Meta-Analysis.

OBJECTIVE: Early initiation of renal replacement therapy (RRT) effect on survival and renal recovery of critically ill patients is still uncertain. We aimed to systematically review current evidence comparing outcomes of early versus late initiation of RRT in critically ill patients. METHODS: We searched the Medline (via Pubmed), LILACS, Science Direct, and CENTRAL databases from inception until November 2016 for randomized clinical trials (RCTs) or observational studies comparing early versus late initiation of RRT in critically ill patients. The primary outcome was mortality. Duration of mechanical ventilation, intensive care unit (ICU) length of stay (LOS), hospital LOS, and renal function recovery were secondary outcomes. Meta-analysis and trial sequential analysis (TSA) were used for the primary outcome. RESULTS: Sixty-two studies were retrieved and analyzed, including 11 RCTs. There was no difference in mortality between early and late initiation of RRT among RCTs (odds ratio [OR] = 0.78; 95% confidence interval [CI]: 0.52-1.19; I2 = 63.1%). Trial sequential analysis of mortality across all RCTs achieved futility boundaries at both 1% and 5% type I error rates, although a subgroup analysis of studies including only acute kidney injury patients was not conclusive. There was also no difference in time on mechanical ventilation, ICU and hospital LOS, or renal recovery among studies. Early initiation of RRT was associated with reduced mortality among prospective (OR = 0.69; 95% CI: 0.49-0.96; I2 = 85.9%) and retrospective (OR = 0.61; 95% CI: 0.41-0.92; I2 = 90.9%) observational studies, both with substantial heterogeneity. However, subgroup analysis excluding low-quality observational studies did not achieve statistical significance. CONCLUSION: Pooled analysis of randomized trials indicates early initiation of RRT is not associated with lower mortality rates. The potential benefit of reduced mortality associated with early initiation of RRT was limited to low-quality observational studies.

Flexible Versus Restrictive Visiting Policies in ICUs: A Systematic Review and Meta-Analysis.

OBJECTIVES: To synthesize data on outcomes related to patients, family members, and ICU professionals by comparing flexible versus restrictive visiting policies in ICUs. DATA SOURCES: Medline, Scopus, and Web of Science. STUDY SELECTION: Observational and randomized studies comparing flexible versus restrictive visiting policies in the ICU and evaluating at least one patient-, family member-, or ICU staff-related outcome. DATA EXTRACTION: Duplicate independent review and data abstraction. DATA SYNTHESIS: Of 16 studies identified for inclusion, seven were meta-analyzed. Most studies were rated as having a moderate risk of bias. Among patients, flexible visiting policies were associated with reduced frequency of delirium (odds ratio, 0.39; 95% CI, 0.22-0.69; I = 0%) and lower severity of anxiety symptoms (mean difference, -2.20; 95% CI, -3.80 to -0.61; I = 71%). Flexible visiting policies were not associated with increased risk of ICU mortality (odds ratio, 0.71; 95% CI, 0.38-1.36; I = 86%), ICU-acquired infections (odds ratio, 0.98; 95% CI, 0.68-1.42; I = 11%), or longer ICU stay (mean difference, -0.26 d; 95% CI, -0.57 to 0.05; I = 54%). Among family members, flexible visiting policies were associated with greater satisfaction. Among ICU professionals, flexible visiting policies were associated with higher burnout levels. CONCLUSIONS: Flexible ICU visiting hours have the potential to reduce delirium and anxiety symptoms among patients and to improve family members' satisfaction. However, they may be associated with an increased risk of burnout among ICU professionals. These conclusions are based on few studies, with small samples and moderate risk of bias.

Characteristics of critically ill patients with cancer associated with intensivist's perception of inappropriateness of ICU admission: A retrospective cohort study.

PURPOSE: Although admitting cancer patients to the ICU is no longer an issue, it may be valuable to identify patients perceived least likely to benefit from admission. Our objective was to investigate factors associated with potentially inappropriate ICU admission. METHODS: Retrospective cohort study of patients with cancer with unplanned ICU admission. We classified admissions as appropriate or potentially inappropriate according to Society of Critical Care Medicine guidelines. We used logistic regression model to assess factors associated with inappropriateness for ICU admission. RESULTS: From 3384 patients, 663 (19.6%) were classified as potentially inappropriate. They received more invasive mechanical ventilation (25.3% vs 12.5%, P < 0.001) and vasopressors (34.4% vs 30.1%, P = 0.034), had higher ICU [3 (2,6) vs 2 (1,4), P < 0.001] length-of-stay, higher ICU (32.7% vs 8.4%, P < 0.001), hospital (71.9% vs 21.3%, P < 0.001), and one-year mortality (97.6% vs 54.7%, P < 0.001) compared with those considered appropriate. Performance status impairment, more severe organ dysfunctions at admission, metastatic disease, and source of ICU admission were the characteristics associated with intensivist's perception of inappropriateness of ICU admission. CONCLUSIONS: These findings may help guide ICU admission policies and triage criteria for end-of-life discussions among hospitalized patients with cancer.

Validation of a low-cost continuous renal replacement therapy dialysate fluid controller for experimental purposes.

BACKGROUND: Continuous renal replacement therapy (CRRT) support is crucial for critically ill patients and it is underexplored in specific situations. Experimental CRRT offers a means to gain insights into these scenarios, but the prohibitive cost of CRRT machines limits their accessibility. This study aimed to develop and validate a low-cost and precise dialysate controller for experimental CRRT. RESULTS: Our results demonstrate a commendable level of precision in affluent flow control, with a robust correlation (R2 = 0.99) for continuous flow and a strong correlation (R2 = 0.95) for intermittent flow. Additionally, we observed acceptable agreement with a bias = 3.4 mL (upper limit 95% = 43.9 mL and lower limit 95% = - 37 mL) for continuous flow and bias = - 20.9 mL (upper limit 95% = 54 mL and lower limit 95% = - 95.7 mL) for intermittent flow, in this way, offering a precise CRRT dose for the subjects. Furthermore, we achieved excellent precision in the cumulative ultrafiltration net (UFnet), with a bias = - 2.8 mL (upper limit 95% = 6.5 mL and lower limit 95% = - 12 mL). These results remained consistent even at low affluent flow rates of 8, 12, and 20 mL/min, which are compatible with CRRT doses of 25-30 mL/kg for medium-sized animals. Moreover, the acceptable precision of our findings persisted when the dialysate controller was subjected to high filter dialysate chamber pressure for an extended duration, up to 797 min. CONCLUSIONS: The low-cost dialysate controller developed and tested in this study offers a precise means of regulating CRRT in experimental settings. Its affordability and accuracy render it a valuable instrument for studying CRRT support in unconventional clinical scenarios, particularly in middle-income countries' experimental ICU laboratories.

Adverse events leading to intensive care unit admission in a low-and-middle-income-country: A prospective cohort study and a systematic review.

INTRODUCTION: Adverse events (AE) are frequent in critical care and could be even more prevalent in LMIC due to a shortage of ICU beds and Human resources. There is limited data on how relevant AE are among the reasons for ICU admission, being all of which published by High-Income-Countries services. Our main goal is to describe the rate of adverse events-related ICU admissions and their preventability in a LMIC scenario, comparing our results with previous data. METHODS: This was a prospective cohort study, during a one-year period, in two general ICUs from a tertiary public academic hospital. Our exposure of interest was ICU admission related to an AE in adult patients, we further characterized their preventability and clinical outcomes. We also performed a systematic review to identify and compare previous published data on ICU admissions due to AE. RESULTS: Among all ICU admissions, 12.1% were related to an AE (9.8% caused by an AE, 2.3% related but not directly caused by an AE). These ICU admissions were not associated with a higher risk of death, but most of them were potentially preventable (70.9% of preventability rate, representing 8.6% of all ICU admissions). The meta-analysis resulted in a proportion of ICU admissions due to AE of 11% (95% CI 6%-16%), with a preventability rate of 54% (95% CI 42%-66%). CONCLUSIONS: In this prospective cohort, adverse events were a relevant reason for ICU admission. This result is consistent with data retrieved from non-LMIC as shown in our meta-analysis. The high preventability rate described reinforces that quality and safety programs could work as a tool to optimize scarce resources.

Changing trends in clinical characteristics and in-hospital mortality of patients with infective endocarditis over four decades.

BACKGROUND: Infective endocarditis continues to be a significant concern and may be undergoing an epidemiological transition. METHODS: Were studied 1804 consecutive episodes of infective endocarditis between 1978 and 2022. The mean age was 48 ( ± 19), and 1162 (64%) patients were male. Temporal trends in demographic data, comorbidities, predisposing conditions, microorganisms, complications and in-hospital death have been studied over the decades (1978-1988, 1989-1999, 2000-2010 and 2011-2022). The outcomes and clinical characteristics were modeled using nonlinear cubic spline functions. FINDINGS: Valve surgery was performed in 50% of the patients and overall in-hospital mortality was 30%. From the first to the fourth decade studied, the average age of patients increased from 29 to 57 years (p < 0.001), with significant declines in the occurrence of rheumatic valvular heart disease (15% to 6%; p < 0.001) and streptococcal infections (46% to 33%; p < 0.001). Healthcare-associated infections have increased (9% to 21%; p < 0.001), as have prosthetic valve endocarditis (26% to 53%; p < 0.001), coagulase-negative staphylococcal infections (4% to 11%; p < 0.001), and related-complications (heart failure, embolic events, and perivalvular abscess; p < 0.001). These changes were associated with a decline in adjusted in-hospital mortality from 34% to 25% (p = 0.019). INTERPRETATION: In the 44 years studied, there was an increase in the mean age of patients, healthcare-related, prosthetic valve, coagulase-negative staphylococci/MRSA infections, and related complications. Notably, these epidemiological changes were associated with a decline in the adjusted in-hospital mortality.

Association of fasting in the first 72 h of intensive care unit stay with outcomes of critically ill patients.

BACKGROUND: Whether fasting early in critical illness course is acceptable is not clear and high-quality data on this topic are lacking. To generate equipoise for future clinical trials and bring additional data to current literature, we compared outcomes of patients fasted during the first 72 h of intensive care unit (ICU) stay to patients receiving any nutrition support during this period. METHODS: Retrospective cohort study of a medical ICU from a tertiary academic center in Brazil. Adult patients treated between November 2017 and February 2022 with an ICU length of stay of ≥5 days were included. Baseline and daily data were retrieved from the prospectively collected administrative database. We did 1:1 propensity score matching to compare patients fasting for at least 72 h with controls. Primary outcome was hospital mortality and secondary outcomes were other resources' use. RESULTS: During the study period, 1591 patients were cared for in this ICU, of which 998 stayed ≥5 days. After excluding readmissions and propensity score matching, 93 patients in the fasting group were matched to 93 controls. Hospital mortality was similar between fasting and matched control groups (odds ratio = 1.04; 95% CI = 0.56-1.94; P > 0.99). Secondary outcomes were not different between groups, including length of stay, days on mechanical ventilation, and incidence of new infections. CONCLUSION: Withholding nutrition support in the first 72 h of ICU stay was not associated with worse outcomes in this cohort of severe critically ill patients.

Intensivist-led ultrasound-guided percutaneous tracheostomy: a phase IV cohort study.

OBJECTIVE: To describe, with a larger number of patients in a real-world scenario following routine implementation, intensivist-led ultrasound-guided percutaneous dilational tracheostomy and the possible risks and complications of the procedure not identified in clinical trials. METHODS: This was a phase IV cohort study of patients admitted to three intensive care units of a quaternary academic hospital who underwent intensivist-led ultrasound-guided percutaneous tracheostomy in Brazil from September 2017 to December 2021. RESULTS: There were 4,810 intensive care unit admissions during the study period; 2,084 patients received mechanical ventilation, and 287 underwent tracheostomy, 227 of which were performed at bedside by the intensive care team. The main reason for intensive care unit admission was trauma, and for perform a tracheostomy it was a neurological impairment or an inability to protect the airways. The median time from intubation to tracheostomy was 14 days. Intensive care residents performed 76% of the procedures. At least one complication occurred in 29.5% of the procedures, the most common being hemodynamic instability and extubation during the procedure, with only 3 serious complications. The intensive care unit mortality was 29.1%, and the hospital mortality was 43.6%. CONCLUSION: Intensivist-led ultrasound-guided percutaneous tracheostomy is feasible out of a clinical trial context with outcomes and complications comparable to those in the literature. Intensivists can acquire this competence during their training but should be aware of potential complications to enhance procedural safety.

Immunothrombosis and COVID-19 ‒ a nested post-hoc analysis from a 3186 patient cohort in a Latin American public reference hospital.

OBJECTIVE: COVID-19 is associated with an elevated risk of thromboembolism and excess mortality. Difficulties with best anticoagulation practices and their implementation motivated the current analysis of COVID-19 patients who developed Venous Thromboembolism (VTE). METHOD: This is a post-hoc analysis of a COVID-19 cohort, described in an economic study already published. The authors analyzed a subset of patients with confirmed VTE. We described the characteristics of the cohort, such as demographics, clinical status, and laboratory results. We tested differences amid two subgroups of patients, those with VTE or not, with the competitive risk Fine and Gray model. RESULTS: Out of 3186 adult patients with COVID-19, 245 (7.7%) were diagnosed with VTE, 174 (5.4%) of them during admission to the hospital. Four (2.3% of these 174) did not receive prophylactic anticoagulation and 19 (11%) discontinued anticoagulation for at least 3 days, resulting in 170 analyzed. During the first week of hospitalization, the laboratory most altered results were C-reactive protein and D-dimer. Patients with VTE were more critical, had a higher mortality rate, worse SOFA score, and, on average, 50% longer hospital stay. CONCLUSION: Proven VTE incidence in this severe COVID-19 cohort was 7.7%, despite 87% of them complying completely with VTE prophylaxis. The clinician must be aware of the diagnosis of VTE in COVID-19, even in patients receiving proper prophylaxis.

Exploring the association of two oxygenators in parallel or in series during respiratory support using extracorporeal membrane oxygenation. / Investigação da associação de dois oxigenadores em paralelo ou em série durante o suporte respiratório com oxigenação por membrana extracorpórea.

OBJECTIVE: To characterize the pressures, resistances, oxygenation, and decarboxylation efficacy of two oxygenators associated in series or in parallel during venous-venous extracorporeal membrane oxygenation support. METHODS: Using the results of a swine severe respiratory failure associated with multiple organ dysfunction venous-venous extracorporeal membrane oxygenation support model and mathematical modeling, we explored the effects on oxygenation, decarboxylation and circuit pressures of in-parallel and in-series associations of oxygenators. RESULTS: Five animals with a median weight of 80kg were tested. Both configurations increased the oxygen partial pressure after the oxygenators. The return cannula oxygen content was also slightly higher, but the impact on systemic oxygenation was minimal using oxygenators with a high rated flow (~ 7L/minute). Both configurations significantly reduced the systemic carbon dioxide partial pressure. As the extracorporeal membrane oxygenation blood flow increased, the oxygenator resistance decreased initially with a further increase with higher blood flows but with a small clinical impact. CONCLUSION: Association of oxygenators in parallel or in series during venous-venous extracorporeal membrane oxygenation support provides a modest increase in carbon dioxide partial pressure removal with a slight improvement in oxygenation. The effect of oxygenator associations on extracorporeal circuit pressures is minimal.

OBJETIVO: Caracterizar as pressões, as resistências, a oxigenação e a eficácia da descarboxilação de dois oxigenadores associados em série ou em paralelo durante o suporte com oxigenação veno-venosa por membrana extracorpórea. MÉTODOS: Usando os resultados de insuficiência respiratória grave em suínos associada à disfunção de múltiplos órgãos, ao modelo de suporte com oxigenação por membrana extracorpórea veno-venosa e à modelagem matemática, exploramos os efeitos na oxigenação, descarboxilação e pressões do circuito de associações de oxigenadores em paralelo e em série. RESULTADOS: Testaram-se cinco animais com peso mediano de 80kg. Ambas as configurações aumentaram a pressão parcial de oxigênio após os oxigenadores. O teor de oxigênio da cânula de retorno também foi ligeiramente maior, mas o efeito na oxigenação sistêmica foi mínimo, usando oxigenadores com alto fluxo nominal (~ 7L/minuto). Ambas as configurações reduziram significativamente a pressão parcial de dióxido de carbono sistêmico. Como o fluxo sanguíneo na oxigenação por membrana extracorpórea aumentou, a resistência do oxigenador diminuiu inicialmente, com aumento posterior, com fluxos sanguíneos mais altos, mas pouco efeito clínico. CONCLUSÃO: A associação de oxigenadores em paralelo ou em série durante o suporte com oxigenação veno-venosa por membrana extracorpórea proporciona um modesto aumento na depuração da pressão parcial de dióxido de carbono, com leve melhora na oxigenação. O efeito das associações de oxigenadores nas pressões de circuitos extracorpóreos é mínimo.

Association between obesity and COVID-19 mortality and length of stay in intensive care unit patients in Brazil: a retrospective cohort study.

The present study aimed to evaluate the association between obesity and COVID-19 mortality and length of stay in ICU patients, and how these associations were modified by age groups. We performed a retrospective multicenter cohort study with data obtained from a hospital-based registry. The sample consisted of 8183 ICU hospitalized patients who tested positive for SARS-CoV-2. Cox proportional models were used to evaluate the association between BMI categories and COVID-19 mortality and generalized linear models for the length of stay in the ICU. After adjusting for confounders, those in the younger group with severe obesity had an increased risk of COVID-19 mortality compared to those with normal/overweight (HR 1.27; 95% CI 1.01-1.61). An increased risk of death was also observed for patients with underweight (HR 3.74; 95% CI 1.39-10.07). For patients aged ≥ 60 year, mild/moderate obesity was associated with reduced mortality risk (HR 0.87; 95% CI 0.78-0.97). For the age group < 60 year, the length of stay in ICU for those patients with severe obesity was 35% higher compared to the normal/overweight category (eß 1.35; 95% CI 1.21-1.51). Conversely, for the survivors in the underweight category, the length of stay in ICU was 51% lower compared to the normal/overweight group (eß 0.49; 95% CI 0.31-0.78). In the age group ≥ 60 year, mild/moderate obesity was associated with an increased length of stay in the ICU (eß 1.10; 95% CI 1.01-1.21), adjusting for confounders. These findings could be helpful for health professionals to identify subgroups at higher risk for worse outcomes.

Clinical outcomes and lung mechanics characteristics between COVID-19 and non-COVID-19-associated acute respiratory distress syndrome: a propensity score analysis of two major randomized trials. / Desfechos clínicos e características da mecânica pulmonar entre a síndrome do desconforto respiratório agudo associada à COVID-19 e a não associada à COVID-19: uma análise de escore de propensão de dois importantes ensaios randomizados.

OBJECTIVE: To compare the lung mechanics and outcomes between COVID-19-associated acute respiratory distress syndrome and non-COVID-19-associated acute respiratory distress syndrome. METHODS: We combined data from two randomized trials in acute respiratory distress syndrome, one including only COVID-19 patients and the other including only patients without COVID-19, to determine whether COVID-19-associated acute respiratory distress syndrome is associated with higher 28-day mortality than non-COVID-19 acute respiratory distress syndrome and to examine the differences in lung mechanics between these two types of acute respiratory distress syndrome. RESULTS: A total of 299 patients with COVID-19-associated acute respiratory distress syndrome and 1,010 patients with non-COVID-19-associated acute respiratory distress syndrome were included in the main analysis. The results showed that non-COVID-19 patients used higher positive end-expiratory pressure (12.5cmH2O; SD 3.2 versus 11.7cmH2O SD 2.8; p < 0.001), were ventilated with lower tidal volumes (5.8mL/kg; SD 1.0 versus 6.5mL/kg; SD 1.2; p < 0.001) and had lower static respiratory compliance adjusted for ideal body weight (0.5mL/cmH2O/kg; SD 0.3 versus 0.6mL/cmH2O/kg; SD 0.3; p = 0.01). There was no difference between groups in 28-day mortality (52.3% versus 58.9%; p = 0.52) or mechanical ventilation duration in the first 28 days among survivors (13 [IQR 5 - 22] versus 12 [IQR 6 - 26], p = 0.46). CONCLUSION: This analysis showed that patients with non-COVID-19-associated acute respiratory distress syndrome have different lung mechanics but similar outcomes to COVID-19-associated acute respiratory distress syndrome patients. After propensity score matching, there was no difference in lung mechanics or outcomes between groups.

OBJETIVO: Comparar a mecânica pulmonar e os desfechos entre a síndrome do desconforto respiratório agudo associada à COVID-19 e a síndrome do desconforto respiratório agudo não associada à COVID-19. MÉTODOS: Combinamos dados de dois ensaios randomizados sobre a síndrome do desconforto respiratório agudo, um incluindo apenas pacientes com COVID-19 e o outro incluindo apenas pacientes sem COVID-19, para determinar se a síndrome do desconforto respiratório agudo associada à COVID-19 está associada à maior mortalidade aos 28 dias do que a síndrome do desconforto respiratório agudo não associada à COVID-19 e também examinar as diferenças na mecânica pulmonar entre esses dois tipos de síndrome do desconforto respiratório agudo. RESULTADOS: Foram incluídos na análise principal 299 pacientes com síndrome do desconforto respiratório agudo associada à COVID-19 e 1.010 pacientes com síndrome do desconforto respiratório agudo não associada à COVID-19. Os resultados mostraram que os pacientes sem COVID-19 utilizaram pressão positiva expiratória final mais alta (12,5cmH2O; DP 3,2 versus 11,7cmH2O; DP 2,8; p < 0,001), foram ventilados com volumes correntes mais baixos (5,8mL/kg; DP 1,0 versus 6,5mL/kg; DP 1,2; p < 0,001) e apresentaram menor complacência respiratória estática ajustada para o peso ideal (0,5mL/cmH2O/kg; DP 0,3 versus 0,6mL/cmH2O/kg; DP 0,3; p = 0,01). Não houve diferença entre os grupos quanto à mortalidade aos 28 dias (52,3% versus 58,9%; p = 0,52) ou à duração da ventilação mecânica nos primeiros 28 dias entre os sobreviventes (13 [IQ 5 - 22] dias versus 12 [IQ 6 - 26] dias; p = 0,46). CONCLUSÃO: Esta análise mostrou que os pacientes com síndrome do desconforto respiratório agudo não associada à COVID-19 têm mecânica pulmonar diferente, mas desfechos semelhantes aos dos pacientes com síndrome do desconforto respiratório agudo associada à COVID-19. Após pareamento por escore de propensão, não houve diferença na mecânica pulmonar e nem nos desfechos entre os grupos.

Bedside clinical data subphenotypes of critically ill COVID-19 patients: a cohort study. / Subfenótipos baseados em dados clínicos de beira-leito de pacientes críticos com COVID-19: um estudo de coorte.

OBJECTIVE: To identify more severe COVID-19 presentations. METHODS: Consecutive intensive care unit-admitted patients were subjected to a stepwise clustering method. RESULTS: Data from 147 patients who were on average 56 ± 16 years old with a Simplified Acute Physiological Score 3 of 72 ± 18, of which 103 (70%) needed mechanical ventilation and 46 (31%) died in the intensive care unit, were analyzed. From the clustering algorithm, two well-defined groups were found based on maximal heart rate [Cluster A: 104 (95%CI 99 - 109) beats per minute versus Cluster B: 159 (95%CI 155 - 163) beats per minute], maximal respiratory rate [Cluster A: 33 (95%CI 31 - 35) breaths per minute versus Cluster B: 50 (95%CI 47 - 53) breaths per minute], and maximal body temperature [Cluster A: 37.4 (95%CI 37.1 - 37.7)°C versus Cluster B: 39.3 (95%CI 39.1 - 39.5)°C] during the intensive care unit stay, as well as the oxygen partial pressure in the blood over the oxygen inspiratory fraction at intensive care unit admission [Cluster A: 116 (95%CI 99 - 133) mmHg versus Cluster B: 78 (95%CI 63 - 93) mmHg]. Subphenotypes were distinct in inflammation profiles, organ dysfunction, organ support, intensive care unit length of stay, and intensive care unit mortality (with a ratio of 4.2 between the groups). CONCLUSION: Our findings, based on common clinical data, revealed two distinct subphenotypes with different disease courses. These results could help health professionals allocate resources and select patients for testing novel therapies.

OBJETIVO: Identificar apresentações mais graves de COVID-19. MÉTODOS: Pacientes consecutivamente admitidos à unidade de terapia intensiva foram submetidos à análise de clusters por meio de método de explorações sequenciais. RESULTADOS: Analisamos os dados de 147 pacientes, com média de idade de 56 ± 16 anos e Simplified Acute Physiological Score 3 de 72 ± 18, dos quais 103 (70%) demandaram ventilação mecânica e 46 (31%) morreram na unidade de terapia intensiva. A partir do algoritmo de análise de clusters, identificaram-se dois grupos bem definidos, com base na frequência cardíaca máxima [Grupo A: 104 (IC95% 99 - 109) batimentos por minuto versus Grupo B: 159 (IC95% 155 - 163) batimentos por minuto], frequência respiratória máxima [Grupo A: 33 (IC95% 31 - 35) respirações por minuto versus Grupo B: 50 (IC95% 47 - 53) respirações por minuto] e na temperatura corpórea máxima [Grupo A: 37,4 (IC95% 37,1 - 37,7)ºC versus Grupo B: 39,3 (IC95% 39,1 - 39,5)ºC] durante o tempo de permanência na unidade de terapia intensiva, assim como a proporção entre a pressão parcial de oxigênio no sangue e a fração inspirada de oxigênio quando da admissão à unidade de terapia intensiva [Grupo A: 116 (IC95% 99 - 133) mmHg versus Grupo B: 78 (IC95% 63 - 93) mmHg]. Os subfenótipos foram distintos em termos de perfis inflamatórios, disfunções orgânicas, terapias de suporte, tempo de permanência na unidade de terapia intensiva e mortalidade na unidade de terapia intensiva (com proporção de 4,2 entre os grupos). CONCLUSÃO: Nossos achados, baseados em dados clínicos universalmente disponíveis, revelaram dois subfenótipos distintos, com diferentes evoluções de doença. Estes resultados podem ajudar os profissionais de saúde na alocação de recursos e seleção de pacientes para teste de novas terapias.