Optimal dosing of heparin for prophylactic anticoagulation in critically ill COVID-19 patients a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The optimal amount of anticoagulation for critically ill COVID-19 patients is controversial. Therefore, we aimed to evaluate the efficacy and safety of escalated doses of anticoagulation in critically ill patients with severe COVID-19. MATERIALS AND METHODS: We conducted a systematic search of three major databases, including PubMed, Cochrane Library, and Embase, from inception to May 2022. Randomized controlled trials (RCTs) were included comparing therapeutic or intermediate doses to standard prophylactic doses of anticoagulants in critically ill COVID-19 patients, with heparins as the only anticoagulation therapy considered. RESULTS: Out of the six RCTs, 2130 patients were administered escalated dose anticoagulation (50.2%) and standard thromboprophylaxis therapy (49.8%). The escalated dose showed no significant impact on mortality (RR, 1.01; 95% CI, 0.90-1.13). Although there was no significant difference in DVT (RR, 0.81; 95% CI, 0.61-1.08), the risk of PE was significantly reduced in patients receiving escalated dose anticoagulation (RR, 0.35; 95% CI, 0.21-0.60), with an increased risk of bleeding events (RR, 1.65; 95% CI, 1.08-2.53). CONCLUSION: This systematic review and meta-analysis fail to support escalated anticoagulation doses to reduce mortality in critically ill COVID-19 patients. However, higher doses of anticoagulants appear to reduce thrombotic events while increasing the risk of bleeding effectively.

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.

IMPACTO-MR: um estudo brasileiro de plataforma nacional para avaliar infecções e multirresistência em unidades de terapia intensiva / IMPACTO-MR: a Brazilian nationwide platform study to assess infections and multidrug resistance in intensive care units

RESUMO Objetivo: Descrever o IMPACTO-MR, um estudo brasileiro de plataforma nacional em unidades de terapia intensiva focado no impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. Métodos: Descrevemos a plataforma IMPACTO-MR, seu desenvolvimento, critérios para seleção das unidades de terapia intensiva, caracterização da coleta de dados, objetivos e projetos de pesquisa futuros a serem realizados na plataforma. Resultados: Os dados principais foram coletados por meio do Epimed Monitor System® e consistiram em dados demográficos, dados de comorbidades, estado funcional, escores clínicos, diagnóstico de internação e diagnósticos secundários, dados laboratoriais, clínicos e microbiológicos e suporte de órgãos durante a internação na unidade de terapia intensiva, entre outros. De outubro de 2019 a dezembro de 2020, 33.983 pacientes de 51 unidades de terapia intensiva foram incluídos no banco de dados principal. Conclusão: A plataforma IMPACTO-MR é um banco de dados clínico brasileiro de unidades de terapia intensiva focado na pesquisa do impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. Essa plataforma fornece dados para o desenvolvimento e pesquisa de unidades de terapia intensiva individuais e ensaios clínicos observacionais e prospectivos multicêntricos.

ABSTRACT Objective: To describe the IMPACTO-MR, a Brazilian nationwide intensive care unit platform study focused on the impact of health care-associated infections due to multidrug-resistant bacteria. Methods: We described the IMPACTO-MR platform, its development, criteria for intensive care unit selection, characterization of core data collection, objectives, and future research projects to be held within the platform. Results: The core data were collected using the Epimed Monitor System® and consisted of demographic data, comorbidity data, functional status, clinical scores, admission diagnosis and secondary diagnoses, laboratory, clinical, and microbiological data, and organ support during intensive care unit stay, among others. From October 2019 to December 2020, 33,983 patients from 51 intensive care units were included in the core database. Conclusion: The IMPACTO-MR platform is a nationwide Brazilian intensive care unit clinical database focused on researching the impact of health care-associated infections due to multidrug-resistant bacteria. This platform provides data for individual intensive care unit development and research and multicenter observational and prospective trials.

A prospective comparison between multidisciplinary healthcare providers' clinical examination and a validated pain scale.

Introduction: Unrecognized pain in the Intensive Care Unit (ICU), due to inadequate assessment and therapeutic management, is associated with increased morbidity and mortality. Despite the availability of validated pain monitoring tools, such as the Critical-Care Pain Observational Tool (CPOT), these scales are not commonly used in clinical practice, with healthcare professionals often relying on their clinical impression. Our study aims to determine the agreement between the pain examination performed by ICU professionals and the CPOT. Methods: Prospective cohort study that included critically ill patients and physicians, nurses and physiotherapists from an ICU in Bahia, Brazil. During bedside clinical rounds, the CPOT score was applied to assess the pain of hospitalized patients, and health professionals were interviewed to ascertain their perception of the patient's pain for a maximum of five consecutive days. Correlations were assessed using the Spearman rank tests. Hierarchical cluster analysis was employed to show the results of CPOT score and pain assessment by healthcare professionals at each study time. And the Kappa statistic was calculated to assess the agreement between the CPOT score vs. the pain assessment by healthcare providers. Results: One hundred one patients were included in the study with median age of 74 years (IQR 61.5-83.5), a predominance of women (55.4%) and a median SAPS 3 score of 45 (IQR 39.5-53.0). The correlation between the professional's pain assessment and the CPOT were mostly statistically significant, ranged from negligible to weak, being the highest index obtained in the evaluation of nurses on day 5 (Kappa index = 0.43, p = 0.005). Physician assessments were significant only in day 1. On the presence of pain, the professionals' assessments and CPOT revealed mild to a moderate agreement. Conclusion: Healthcare professional's pain assessment displayed a weak positive correlation with a validated pain scale and poor agreement amongst members of the ICU team, particularly when the pain was felt to be absent. Thus, this study highlights the importance of routine tools for pain assessment in the ICU for all members of multidisciplinary teams.

Immunomodulatory and Anti-fibrotic Effects Following the Infusion of Umbilical Cord Mesenchymal Stromal Cells in a Critically Ill Patient With COVID-19 Presenting Lung Fibrosis: A Case Report.

Background: The patients with coronavirus disease 2019 (COVID-19) associated with severe acute respiratory distress syndrome (ARDS) may require prolonged mechanical ventilation which often results in lung fibrosis, thus worsening the prognosis and increasing fatality rates. A mesenchymal stromal cell (MSC) therapy may decrease lung inflammation and accelerate recovery in COVID-19. In this context, some studies have reported the effects of MSC therapy for patients not requiring invasive ventilation or during the first hours of tracheal intubation. However, this is the first case report presenting the reduction of not only lung inflammation but also lung fibrosis in a critically ill long-term mechanically ventilated patient with COVID-19. Case Presentation: This is a case report of a 30-year-old male patient with COVID-19 under invasive mechanical ventilation for 14 days in the intensive care unit (ICU), who presented progressive clinical deterioration associated with lung fibrosis. The symptoms onset was 35 days before MSC therapy. The patient was treated with allogenic human umbilical-cord derived MSCs [5 × 107 (2 doses 2 days interval)]. No serious adverse events were observed during and after MSC administration. After MSC therapy, PaO2/FiO2 ratio increased, the need for vasoactive drugs reduced, chest CT scan imaging, which initially showed signs of bilateral and peripheral ground-glass, as well as consolidation and fibrosis, improved, and the systemic mediators associated with inflammation decreased. Modulation of the different cell populations in peripheral blood was also observed, such as a reduction in inflammatory monocytes and an increase in the frequency of patrolling monocytes, CD4+ lymphocytes, and type 2 classical dendritic cells (cDC2). The patient was discharged 13 days after the cell therapy. Conclusions: Mesenchymal stromal cell therapy may be a promising option in critically ill patients with COVID-19 presenting both severe lung inflammation and fibrosis. Further clinical trials could better assess the efficacy of MSC therapy in critically ill patients with COVID-19 with lung fibrosis associated with long-term mechanical ventilation.

Unplanned Transfers From Intermediate Care Units to Intensive Care Units: A Cohort Study.

This study evaluated unplanned transfers from the intermediate care unit (IMCU) to the intensive care unit (ICU) among urgent admissions. This retrospective, observational study was conducted in 2 ICUs and 1 IMCU. Three patterns of urgent admission were assessed: admissions to the ICU only, admissions to the IMCU only, and admissions to the IMCU with subsequent transfer to the ICU. Of 5296 admissions analyzed, 1396 patients (26.4%) were initially admitted to the IMCU. Of these, 172 (12.3%) were transferred from the IMCU to the ICU. Mortality was higher in patients transferred from the IMCU to the ICU than in the 3900 ICU-only patients (odds ratio, 3.22; 95% CI, 1.52-6.80). Most transfers from the IMCU to the ICU (135; 78.5%) were due to deterioration of the condition for which the patient was admitted. Patient transfers from the IMCU to the ICU were common, were associated with increased hospital mortality, and were mostly due to deterioration in the condition that was the reason for admission.

Is there a place for mesenchymal stromal cell-based therapies in the therapeutic armamentarium against COVID-19?

The COVID-19 pandemic, caused by the rapid global spread of the novel coronavirus (SARS-CoV-2), has caused healthcare systems to collapse and led to hundreds of thousands of deaths. The clinical spectrum of COVID-19 is not only limited to local pneumonia but also represents multiple organ involvement, with potential for systemic complications. One year after the pandemic, pathophysiological knowledge has evolved, and many therapeutic advances have occurred, but mortality rates are still elevated in severe/critical COVID-19 cases. Mesenchymal stromal cells (MSCs) can exert immunomodulatory, antiviral, and pro-regenerative paracrine/endocrine actions and are therefore promising candidates for MSC-based therapies. In this review, we discuss the rationale for MSC-based therapies based on currently available preclinical and clinical evidence of safety, potential efficacy, and mechanisms of action. Finally, we present a critical analysis of the risks, limitations, challenges, and opportunities that place MSC-based products as a therapeutic strategy that may complement the current arsenal against COVID-19 and reduce the pandemic's unmet medical needs.

Resuscitation fluid practices in Brazilian intensive care units: a secondary analysis of Fluid-TRIPS. / Práticas de ressuscitação volêmica em unidades de terapia intensiva brasileiras: uma análise secundária do estudo Fluid-TRIPS.

OBJECTIVE: To describe fluid resuscitation practices in Brazilian intensive care units and to compare them with those of other countries participating in the Fluid-TRIPS. METHODS: This was a prospective, international, cross-sectional, observational study in a convenience sample of intensive care units in 27 countries (including Brazil) using the Fluid-TRIPS database compiled in 2014. We described the patterns of fluid resuscitation use in Brazil compared with those in other countries and identified the factors associated with fluid choice. RESULTS: On the study day, 3,214 patients in Brazil and 3,493 patients in other countries were included, of whom 16.1% and 26.8% (p < 0.001) received fluids, respectively. The main indication for fluid resuscitation was impaired perfusion and/or low cardiac output (Brazil: 71.7% versus other countries: 56.4%, p < 0.001). In Brazil, the percentage of patients receiving crystalloid solutions was higher (97.7% versus 76.8%, p < 0.001), and 0.9% sodium chloride was the most commonly used crystalloid (62.5% versus 27.1%, p < 0.001). The multivariable analysis suggested that the albumin levels were associated with the use of both crystalloids and colloids, whereas the type of fluid prescriber was associated with crystalloid use only. CONCLUSION: Our results suggest that crystalloids are more frequently used than colloids for fluid resuscitation in Brazil, and this discrepancy in frequencies is higher than that in other countries. Sodium chloride (0.9%) was the crystalloid most commonly prescribed. Serum albumin levels and the type of fluid prescriber were the factors associated with the choice of crystalloids or colloids for fluid resuscitation.

OBJETIVO: Descrever as práticas de ressuscitação volêmica em unidades de terapia intensiva brasileiras e compará-las com as de outros países participantes do estudo Fluid-TRIPS. MÉTODOS: Este foi um estudo observacional transversal, prospectivo e internacional, de uma amostra de conveniência de unidades de terapia intensiva de 27 países (inclusive o Brasil), com utilização da base de dados Fluid-TRIPS compilada em 2014. Descrevemos os padrões de ressuscitação volêmica utilizados no Brasil em comparação com os de outros países e identificamos os fatores associados com a escolha dos fluidos. RESULTADOS: No dia do estudo, foram incluídos 3.214 pacientes do Brasil e 3.493 pacientes de outros países, dos quais, respectivamente, 16,1% e 26,8% (p < 0,001) receberam fluidos. A principal indicação para ressuscitação volêmica foi comprometimento da perfusão e/ou baixo débito cardíaco (Brasil 71,7% versus outros países 56,4%; p < 0,001). No Brasil, a percentagem de pacientes que receberam soluções cristaloides foi mais elevada (97,7% versus 76,8%; p < 0,001), e solução de cloreto de sódio a 0,9% foi o cristaloide mais comumente utilizado (62,5% versus 27,1%; p < 0,001). A análise multivariada sugeriu que os níveis de albumina se associaram com o uso tanto de cristaloides quanto de coloides, enquanto o tipo de prescritor dos fluidos se associou apenas com o uso de cristaloides. CONCLUSÃO: Nossos resultados sugerem que cristaloides são usados mais frequentemente do que coloides para ressuscitação no Brasil, e essa discrepância, em termos de frequências, é mais elevada do que em outros países. A solução de cloreto de sódio 0,9% foi o cristaloide mais frequentemente prescrito. Os níveis de albumina sérica e o tipo de prescritor de fluidos foram os fatores associados com a escolha de cristaloides ou coloides para a prescrição de fluidos.

Realistic simulation is associated with healthcare professionals' increased self-perception of confidence in providing acute stroke care: a before-after controlled study.

BACKGROUND: Simulations are becoming widely used in medical education, but there is little evidence of their effectiveness on neurocritical care. Because acute stroke is a neurological emergency demanding prompt attention, it is a promising candidate for simulation training. OBJECTIVE: To assess the impact of a stroke realistic simulation course on clinicians' self-perception of confidence in the management of acute stroke. METHODS: We conducted a controlled, before-after study. For our intervention, 17 healthcare professionals participated in a stroke realistic simulation course. As controls, participants were chosen from a convenience sample of attendees to the courses Emergency Neurologic Life Support (ENLS) (18 participants) and Neurosonology (20 participants). All participants responded pre- and post-test questionnaires evaluating their self-perception of confidence in acute stroke care, ranging from 10 to 50 points. We evaluated the variation between pre- and post-test results to assess the change on trainees' self-perception of confidence in the management of acute stroke. Multivariate analysis was performed to control for potential confounders. RESULTS: Forty-six (83.63%) subjects completed both questionnaires. The post-test scores were higher than those from the pretests in the stroke realistic simulation course group [pretest median (interquartile range - IQR): 41.5 (36.7-46.5) and post-test median (IQR): 47 (44.7-48); p=0.033], but not in the neurosonology [pretest median (IQR): 46 (44-47) and post-test median (IQR): 46 (44-47); p=0.739] or the ENLS [pretest median (IQR): 46.5 (39-48.2), post-test median (IQR): 47 (40.2-49); p=0.317] groups. Results were maintained after adjustment for covariates. CONCLUSIONS: This stroke realistic simulation course was associated with an improvement on trainees' self-perception of confidence in providing acute stroke care.

Realistic simulation is associated with healthcare professionals' increased self-perception of confidence in providing acute stroke care: a before-after controlled study / Simulação realística é associada a aumento na autopercepção de segurança de profissionais de saúde no atendimento a pacientes com acidente vascular cerebral agudo: um estudo antes-depois controlado

ABSTRACT Background: Simulations are becoming widely used in medical education, but there is little evidence of their effectiveness on neurocritical care. Because acute stroke is a neurological emergency demanding prompt attention, it is a promising candidate for simulation training. Objective: To assess the impact of a stroke realistic simulation course on clinicians' self-perception of confidence in the management of acute stroke. Methods: We conducted a controlled, before-after study. For our intervention, 17 healthcare professionals participated in a stroke realistic simulation course. As controls, participants were chosen from a convenience sample of attendees to the courses Emergency Neurologic Life Support (ENLS) (18 participants) and Neurosonology (20 participants). All participants responded pre- and post-test questionnaires evaluating their self-perception of confidence in acute stroke care, ranging from 10 to 50 points. We evaluated the variation between pre- and post-test results to assess the change on trainees' self-perception of confidence in the management of acute stroke. Multivariate analysis was performed to control for potential confounders. Results: Forty-six (83.63%) subjects completed both questionnaires. The post-test scores were higher than those from the pretests in the stroke realistic simulation course group [pretest median (interquartile range - IQR): 41.5 (36.7-46.5) and post-test median (IQR): 47 (44.7-48); p=0.033], but not in the neurosonology [pretest median (IQR): 46 (44-47) and post-test median (IQR): 46 (44-47); p=0.739] or the ENLS [pretest median (IQR): 46.5 (39-48.2), post-test median (IQR): 47 (40.2-49); p=0.317] groups. Results were maintained after adjustment for covariates. Conclusions: This stroke realistic simulation course was associated with an improvement on trainees' self-perception of confidence in providing acute stroke care.

RESUMO Introdução: Simulações são amplamente utilizadas na educação médica, mas há pouca evidência de sua eficácia no tratamento de pacientes neurocríticos. Como o acidente vascular cerebral agudo (AVC) é uma patologia que requer atendimento imediato, o uso de simulação pode ser uma ferramenta útil no treinamento do manejo desses pacientes. Objetivo: Avaliar o impacto do uso de simulação realística na autopercepção de segurança no atendimento a pacientes vítimas de AVC agudo. Métodos: Estudo antes-depois controlado. No grupo da intervenção, 17 profissionais da área de saúde participaram de um curso de simulação realística de atendimento a pacientes com AVC. Como controles, os participantes foram escolhidos a partir de uma amostra de conveniência composta por 18 participantes do curso Emergency Neurologic Life Support (ENLS) e 20 participantes de um curso de Neurossonologia. Foram respondidos questionários antes e após o curso para avaliar a autopercepção de segurança no atendimento a pacientes vítimas de AVC agudo, variando de 10 a 50 pontos. Foi avaliada a variação entre os resultados pré- e pós-teste, para avaliar a mudança na autopercepção de confiança do trainee no manejo do AVC agudo. Análise multivariada foi realizada para controlar possíveis fatores de confusão. Resultados: Quarenta e seis (83,63%) participantes responderam aos questionários. A pontuação no questionário pós-curso foi maior do que a obtida no questionário pré-curso no grupo de participantes do curso de simulação realística em AVC [mediana do questionário pré-curso: 41,5 (36,7-46,5) e mediana do questionário pós-curso: 47,0 (44,7-48,0); p=0,033]. Essa diferença não foi observada no curso de Neurossonologia [mediana pré-curso (IQR): 46,0 (44,0-47,00), mediana pós-curso (IQR): 46,0 (44,0-47,0); p=0,739] nem no ENLS [mediana pré-curso (IQR): 46,5 (39,0-48,2) mediana pós-curso (IQR): 47,0 (40,2-49,0); p=0,317]. Esses resultados persistiram após ajuste das variáveis. Conclusão: O curso de simulação realística em AVC foi associado a um aumento na autopercepção de segurança dos participantes em atender pacientes vítimas de AVC agudo.

Eficácia e segurança da milrinona no tratamento do vasoespasmo cerebral após hemorragia subaracnóidea: uma revisão sistemática / Efficacy and safety of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage: a systematic review

RESUMO Objetivo: Revisar sistematicamente a evidência atual da eficácia de milrinona no tratamento do vasoespasmo cerebral após hemorragia subaracnóidea. Métodos: Triaram-se as bases de dados Pubmed®, Cochrane e Embase quanto a artigos publicados entre abril de 2001 e fevereiro de 2019. Dois revisores independentes realizaram uma triagem metodológica da qualidade e a extração dos dados dos estudos. Resultados: Encontraram-se 22 estudos considerados relevantes, sendo que apenas um deles era um ensaio randomizado controlado. Os estudos demonstraram acentuada heterogeneidade e debilidade de seus critérios metodológicos. A maioria dos pacientes apresentava vasoespasmo moderado a grave. O principal método para diagnóstico do vasoespasmo foi a angiografia. Em três estudos, realizou-se administração de milrinona por via intra-arterial; em nove estudos, a administração foi endovenosa, e, em seis estudos, utilizaram-se ambas as vias de administração. A via intratecal foi utilizada em dois estudos, em um estudo, a administração foi realizada via cisterna e, em um estudo, a via de administração foi a endovascular. Os efeitos colaterais de milrinona foram descritos em seis estudos. Vinte e um estudos indicaram a resolução do vasoespasmo. Conclusão: A evidência atual indica que o uso de milrinona teve um papel no tratamento do vasoespasmo após hemorragia subaracnóidea aneurismática. Contudo, só foi realizado um ensaio randomizado controlado, com baixo nível de qualidade. Nossos achados indicam a necessidade de futuros estudos randomizados controlados com desfechos centrados no paciente, com o fim de proporcionar recomendações definitivas.

ABSTRACT Objective: To systematically review the current evidence on the efficacy of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage. Methods: The Pubmed®, Cochrane and Embase databases were screened for articles published from April 2001 to February 2019. Two independent reviewers performed the methodological quality screening and data extraction of the studies. Results: Twenty-two studies were found to be relevant, and only one of these was a randomized control trial. Studies showed marked heterogeneity and weaknesses in key methodological criteria. Most patients presented with moderate to severe vasospasm. Angiography was the main method of diagnosing vasospasm. Intra-arterial administration of milrinone was performed in three studies, intravenous administration was performed in nine studies, and both routes of administration in six studies; the intrathecal route was used in two studies, the cisternal route in one study and endovascular administration in one study. The side effects of milrinone were described in six studies. Twenty-one studies indicated resolution of vasospasm. Conclusion: The current evidence indicates that milrinone may have a role in treatment of vasospasm after aneurysmal subarachnoid hemorrhage. However, only one randomized control trial was performed, with a low quality level. Our findings indicate the need for future randomized control trials with patient-centered outcomes to provide definitive recommendations.

Ultrasound-Guided Percutaneous Dilational Tracheostomy: A Systematic Review of Randomized Controlled Trials and Meta-Analysis.

INTRODUCTION: Percutaneous dilational tracheostomy (PDT) is a common and increasingly used procedure in the intensive care unit (ICU). It is usually performed with bronchoscopy guidance. Ultrasound has emerged as a useful tool in order to assist PDT, potentially improving its success rate and reducing procedural-related complications. OBJECTIVE: To investigate whether the ultrasound-guided PDT is equivalent or superior to the bronchoscopy-guided or anatomical landmarks-guided PDT with regard to procedural-related and clinical complications. METHODS: A systematic review of randomized clinical trials was conducted comparing an ultrasound-guided PDT to the control groups (either a bronchoscopy-guided PDT or an anatomical landmark-guided PDT) in patients undergoing a PDT in the ICU. The primary outcome was the incidence of major procedural-related and clinical complication rates. The secondary outcome was the incidence of minor complication rates. Random-effect meta-analyzes were used to pool the results. RESULTS: Four studies fulfilled the inclusion criteria and they were analyzed. The studies included 588 participants. There were no differences in the major complication rates between the patients who were assigned to the ultrasound-guided PDT when compared to the control groups (pooled risk ratio [RR]: 0.48; 95% confidence interval [CI]: 0.13-1.71, I2 = 0%). The minor complication rates were not different between the groups, but they had a high heterogeneity (pooled RR: 0.49; 95% CI 0.16-1.50; I2 = 85%). The sensitivity analyzes that only included the randomized controlled trials that used a landmark-guided PDT as the control group showed lower rates of minor complications in the ultrasound-guided PDT group (pooled RR: 0.55; 95% CI: 0.31-0.98, I2 = 0%). CONCLUSION: The ultrasound-guided PDT seems to be safe and it is comparable to the bronchoscopy-guided PDT regarding the major and minor procedural-related or clinical complications. It also seems to reduce the minor complications when compared to the anatomical landmark-guided PDT.

Efficacy and safety of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage: a systematic review. / Eficácia e segurança da milrinona no tratamento do vasoespasmo cerebral após hemorragia subaracnóidea: uma revisão sistemática.

OBJECTIVE: To systematically review the current evidence on the efficacy of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage. METHODS: The Pubmed®, Cochrane and Embase databases were screened for articles published from April 2001 to February 2019. Two independent reviewers performed the methodological quality screening and data extraction of the studies. RESULTS: Twenty-two studies were found to be relevant, and only one of these was a randomized control trial. Studies showed marked heterogeneity and weaknesses in key methodological criteria. Most patients presented with moderate to severe vasospasm. Angiography was the main method of diagnosing vasospasm. Intra-arterial administration of milrinone was performed in three studies, intravenous administration was performed in nine studies, and both routes of administration in six studies; the intrathecal route was used in two studies, the cisternal route in one study and endovascular administration in one study. The side effects of milrinone were described in six studies. Twenty-one studies indicated resolution of vasospasm. CONCLUSION: The current evidence indicates that milrinone may have a role in treatment of vasospasm after aneurysmal subarachnoid hemorrhage. However, only one randomized control trial was performed, with a low quality level. Our findings indicate the need for future randomized control trials with patient-centered outcomes to provide definitive recommendations.

OBJETIVO: Revisar sistematicamente a evidência atual da eficácia de milrinona no tratamento do vasoespasmo cerebral após hemorragia subaracnóidea. MÉTODOS: Triaram-se as bases de dados Pubmed®, Cochrane e Embase quanto a artigos publicados entre abril de 2001 e fevereiro de 2019. Dois revisores independentes realizaram uma triagem metodológica da qualidade e a extração dos dados dos estudos. RESULTADOS: Encontraram-se 22 estudos considerados relevantes, sendo que apenas um deles era um ensaio randomizado controlado. Os estudos demonstraram acentuada heterogeneidade e debilidade de seus critérios metodológicos. A maioria dos pacientes apresentava vasoespasmo moderado a grave. O principal método para diagnóstico do vasoespasmo foi a angiografia. Em três estudos, realizou-se administração de milrinona por via intra-arterial; em nove estudos, a administração foi endovenosa, e, em seis estudos, utilizaram-se ambas as vias de administração. A via intratecal foi utilizada em dois estudos, em um estudo, a administração foi realizada via cisterna e, em um estudo, a via de administração foi a endovascular. Os efeitos colaterais de milrinona foram descritos em seis estudos. Vinte e um estudos indicaram a resolução do vasoespasmo. CONCLUSÃO: A evidência atual indica que o uso de milrinona teve um papel no tratamento do vasoespasmo após hemorragia subaracnóidea aneurismática. Contudo, só foi realizado um ensaio randomizado controlado, com baixo nível de qualidade. Nossos achados indicam a necessidade de futuros estudos randomizados controlados com desfechos centrados no paciente, com o fim de proporcionar recomendações definitivas.

Dynamic Autoregulation is Impaired in Circulatory Shock.

BACKGROUND: Circulatory shock is a life-threatening disorder that is associated with high mortality, with a state of systemic and tissue hypoperfusion that can lead to organ failure, including the brain, where altered mental state is often observed. We hypothesized that cerebral autoregulation (CA) is impaired in patients with circulatory shock. METHODS: Adult patients with circulatory shock and healthy controls were included. Cerebral blood flow velocity (CBFV, transcranial Doppler ultrasound) and arterial blood pressure (BP, Finometer or intra-arterial line) were continuously recorded during 5 min in both groups. Autoregulation Index (ARI) was estimated from the CBFV response to a step change in BP, derived by transfer function analysis; ARI ≤ 4 was considered impaired CA. The relationship between organ dysfunction, assessed with the Sequential Organ Failure Assessment (SOFA) score and the ARI, was assessed with linear regression. RESULTS: Twenty-five shock patients and 28 age-matched healthy volunteers were studied. The mean ±â€ŠSD SOFA score was 10.8 ±â€Š4.3. Shock patients compared with control subjects had lower ARI values (4.0 ±â€Š2.1 vs. 5.9 ±â€Š1.5, P = 0.001). Impaired CA was more common in shock patients (44.4% vs. 7.1%, P = 0.003). There was a significant inverse relationship between the ARI and the SOFA score (R = -0.63, P = 0.0008). CONCLUSIONS: These results suggest that circulatory shock is often associated with impaired CA and that the severity of CA alterations is correlated with the degree of multiple organ failure, reinforcing the need to monitor cerebral hemodynamics in patients with circulatory shock.

Intravenous administration of Milrinone, as an alternative approach to treat vasospasm in subarachnoid hemorrhage: A case report of transcranial Doppler monitoring.

This case illustrates the importance and potential of having TCD monitoring in intensive care. This easy-to-use, safe, low-cost, and bedside tool allows evaluation of the safety and feasibility of an alternative treatment of VSP in SCH and demonstrates the potential to avoid the use of angiography, a high cost, invasive procedure.

Transfusion requirements after head trauma: a randomized feasibility controlled trial.

BACKGROUND: Anemia is frequent among patients with traumatic brain injury (TBI) and is associated with an increased risk of poor outcome. The optimal hemoglobin concentration to trigger red blood cell (RBC) transfusion in patients with TBI is not clearly defined. METHODS: All eligible consecutive adult patients admitted to the intensive care unit (ICU) with moderate or severe TBI were randomized to a "restrictive" (hemoglobin transfusion threshold of 7 g/dL), or a "liberal" (threshold 9 g/dL) transfusion strategy. The transfusion strategy was continued for up to 14 days or until ICU discharge. The primary outcome was the mean difference in hemoglobin between groups. Secondary outcomes included transfusion requirements, intracranial pressure management, cerebral hemodynamics, length of stay, mortality and 6-month neurological outcome. RESULTS: A total of 44 patients were randomized, 21 patients to the liberal group and 23 to the restrictive group. There were no baseline differences between the groups. The mean hemoglobin concentrations during the 14-day period were 8.4 ± 1.0 and 9.3 ± 1.3 (p < 0.01) in the restrictive and liberal groups, respectively. Fewer RBC units were administered in the restrictive than in the liberal group (35 vs. 66, p = 0.02). There was negative correlation (r = - 0.265, p < 0.01) between hemoglobin concentration and middle cerebral artery flow velocity as evaluated by transcranial Doppler ultrasound and the incidence of post-traumatic vasospasm was significantly lower in the liberal strategy group (4/21, 3% vs. 15/23, 65%; p < 0.01). Hospital mortality was higher in the restrictive than in the liberal group (7/23 vs. 1/21; p = 0.048) and the liberal group tended to have a better neurological status at 6 months (p = 0.06). CONCLUSIONS: The trial reached feasibility criteria. The restrictive group had lower hemoglobin concentrations and received fewer RBC transfusions. Hospital mortality was lower and neurological status at 6 months favored the liberal group. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02203292 . Registered on 29 July 2014.

Prognostic ability of quick-SOFA across different age groups of patients with suspected infection outside the intensive care unit: A cohort study.

OBJECTIVES: Sepsis identification in older patients is challenging. We evaluated the performance of qSOFA across different age groups of patients with suspected infection outside the intensive care unit (ICU). METHODS: Retrospective cohort in a tertiary hospital in Brazil, from January 2016 to December 2016. Outcomes were hospital mortality, ICU admission and bacteremia. Performance of qSOFA was compared over three age groups: (1) reference: ≤65 years, (2) old: 65 to 79 years and (3) very old: ≥80 years. RESULTS: There were 420 patients in the study, of which 259 (61.7%) were ≤65 years, 80 (19%) were 65 to 79 years and 81 (19.3%) were ≥80 years. Old and very old patients had higher qSOFA scores and lower SIRS scores. Overall, qSOFA ≥2 was associated to hospital mortality [OR (95% CI) = 5.8 (3.3-10.4), p < 0.001], ICU admission [OR (95% CI) = 2.7 (1.6-4.6), p < 0.001] and bacteremia [OR (95% CI) = 3.1 (1.7-5.8), p < 0.001]. Those associations were stronger in old and very old patients. qSOFA and SIRS demonstrated overall AUROCs for hospital mortality of 0.72 and 0.50, respectively. CONCLUSION: qSOFA demonstrated good overall accuracy and was more strongly associated to outcomes in old and very old patients, when compared to younger patients.

Inclusion and definition of acute renal dysfunction in critically ill patients in randomized controlled trials: a systematic review.

BACKGROUND: In evidence-based medicine, multicenter, prospective, randomized controlled trials (RCTs) are the gold standard for evaluating treatment benefits and ensuring the effectiveness of interventions. Patient-centered outcomes, such as mortality, are most often the preferred evaluated outcomes. While there is currently agreement on how to classify renal dysfunction in critically ill patients , the application frequency of this new classification system in RCTs has not previously been evaluated. In this study, we aim to assess the definition of renal dysfunction in multicenter RCTs involving critically ill patients that included mortality as a primary endpoint. METHODS: A comprehensive search was conducted for publications reporting multicenter randomized controlled trials (RCTs) involving adult patients in intensive care units (ICUs) that included mortality as a primary outcome. MEDLINE and PUBMED were queried for relevant articles in core clinical journals published between May 2004 and December 2017. RESULTS: Of 418 articles reviewed, 46 multicenter RCTs with a primary endpoint related to mortality were included. Thirty-six (78.3%) of the trial reports provided information on renal function in the participants. Only seven articles (15.2%) included mean or median serum creatinine levels, mean creatinine clearance or estimated glomerular filtration rates. Sequential organ failure assessment (SOFA) score was the most commonly used definition of renal dysfunction (20 studies; 43.5%). Risk, Injury, Failure, Loss, End-stage renal disease (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease Improving Global Outcomes (KDIGO) criteria were used in five (10.9%) trials. In thirteen trials (28.3%), no renal dysfunction criteria were reported. Only one trial excluded patients with renal dysfunction, and it used urinary output or need for renal replacement therapy (RRT) as criteria for this diagnosis. CONCLUSION: The presence of renal dysfunction was included as a baseline patient characteristic in most RCTs. The RIFLE, AKIN and KDIGO classification systems were infrequently used; renal dysfunction was generally defined using the SOFA score.

Heart conduction system defects and sustained ventricular tachycardia complications in a patient with granulomatosis with polyangiitis. A case report and literature review. / Distúrbios de condução cardíaca e taquicardia ventricular como complicação da granulomatose com poliangiíte em uma paciente. Relato de caso e revisão da literatura.

Granulomatosis with polyangiitis is a rare systemic inflammatory disorder characterized by vasculitis of the small arteries, the arterioles and the capillaries together with necrotizing granulomatous lesions. This case reports on a young female patient, previously diagnosed with granulomatosis with polyangiitis, who was admitted to the intensive care unit with seizures and hemodynamic instability due to a complete atrioventricular heart block. The event was associated with multiple episodes of sustained ventricular tachycardia without any structural heart changes or electrolyte disturbances. In the intensive care unit, the patient was fitted with a provisory pacemaker, followed by immunosuppression with corticosteroids and immunobiological therapy, resulting in a total hemodynamic improvement. Severe conduction disorders in patients presenting granulomatosis with polyangiitis are rare but can contribute to increased morbidity. Early detection and specific intervention can prevent unfavorable outcomes, specifically in the intensive care unit.

A granulomatose com poliangiíte é um raro distúrbio inflamatório sistêmico que se caracteriza por vasculite de pequenas artérias, arteríolas e capilares, associada a lesões granulomatosas necrotizantes. Este artigo relata o caso de uma paciente com diagnóstico prévio de granulomatose com poliangiíte, admitida à unidade de terapia intensiva com quadro de crises convulsivas e instabilidade hemodinâmica em razão de bloqueio atrioventricular completo. Estas manifestações se associaram a múltiplos episódios de taquicardia ventricular sustentada; não havia alterações estruturais cardíacas, nem se detectaram distúrbios hidroeletrolíticos. Na unidade de terapia intensiva, a paciente foi submetida à implantação de marca-passo provisório, imunossupressão com uso de corticosteroides e terapia imunobiológica, resultando em melhora hemodinâmica completa. Distúrbios graves da condução cardíaca em pacientes com granulomatose com poliangiíte são raros, mas associam-se à grande morbidade. O reconhecimento precoce e o uso de intervenções específicas são capazes de prevenir a ocorrência de desfechos desfavoráveis, especialmente na unidade de terapia intensiva.