Long-term outcomes for epidemic viral pneumonia survivors after discharge from the intensive care unit: a systematic review.

OBJECTIVE: To review the long-term outcomes (functional status and psychological sequelae) of survivors of critical illnesses due to epidemic viral pneumonia before the COVID-19 pandemic and to establish a benchmark for comparison of the COVID-19 long-term outcomes. METHODS: This systematic review of clinical studies reported the long-term outcomes in adults admitted to intensive care units who were diagnosed with viral epidemic pneumonia. An electronic search was performed using databases: MEDLINE®, Web of Science™, LILACS/IBECS, and EMBASE. Additionally, complementary searches were conducted on the reference lists of eligible studies. The quality of the studies was assessed using the Newcastle-Ottawa Scale. The results were grouped into tables and textual descriptions. RESULTS: The final analysis included 15 studies from a total of 243 studies. This review included 771 patients with Influenza A, Middle East Respiratory Syndrome, and Severe Acute Respiratory Syndrome. It analyzed the quality of life, functionality, lung function, mortality, rate of return to work, rehospitalization, and psychiatric symptoms. The follow-up periods ranged from 1 to 144 months. We found that the quality of life, functional capacity, and pulmonary function were below expected standards. CONCLUSION: This review revealed great heterogeneity between studies attributed to different scales, follow-up time points, and methodologies. However, this systematic review identified negative long-term effects on patient outcomes. Given the possibility of future pandemics, it is essential to identify the long-term effects of viral pneumonia outbreaks. This review was not funded. Prospero database registration: (www.crd.york.ac.uk/prospero) under registration ID CRD42021190296.

Long-term outcomes for epidemic viral pneumonia survivors after discharge from the intensive care unit: a systematic review

ABSTRACT Objective To review the long-term outcomes (functional status and psychological sequelae) of survivors of critical illnesses due to epidemic viral pneumonia before the COVID-19 pandemic and to establish a benchmark for comparison of the COVID-19 long-term outcomes. Methods This systematic review of clinical studies reported the long-term outcomes in adults admitted to intensive care units who were diagnosed with viral epidemic pneumonia. An electronic search was performed using databases: MEDLINE®, Web of Science™, LILACS/IBECS, and EMBASE. Additionally, complementary searches were conducted on the reference lists of eligible studies. The quality of the studies was assessed using the Newcastle-Ottawa Scale. The results were grouped into tables and textual descriptions. Results The final analysis included 15 studies from a total of 243 studies. This review included 771 patients with Influenza A, Middle East Respiratory Syndrome, and Severe Acute Respiratory Syndrome. It analyzed the quality of life, functionality, lung function, mortality, rate of return to work, rehospitalization, and psychiatric symptoms. The follow-up periods ranged from 1 to 144 months. We found that the quality of life, functional capacity, and pulmonary function were below expected standards. Conclusion This review revealed great heterogeneity between studies attributed to different scales, follow-up time points, and methodologies. However, this systematic review identified negative long-term effects on patient outcomes. Given the possibility of future pandemics, it is essential to identify the long-term effects of viral pneumonia outbreaks. This review was not funded. Prospero database registration: (www.crd.york.ac.uk/prospero) under registration ID CRD42021190296.

Standardized Brazilian green propolis extract (EPP-AF®) in COVID-19 outcomes: a randomized double-blind placebo-controlled trial.

SARS-CoV-2 and its different variants caused a "wave and wave" pandemic pattern. During the first wave we demonstrated that standardized Brazilian green propolis extract (EPP-AF®) reduces length of hospital stay in adult patients with COVID-19. Afterwards, we decided to evaluate the impact of EPP-AF in hospitalized patients during the third wave of the pandemic. BeeCovid2 was a randomized, double-blind, placebo-controlled clinical trial in hospitalized COVID-19 adult patients. Patients were allocated to receive an oral dose of 900 mg/day of EPP-AF® or placebo for 10 days. The primary outcome was length of hospital stay. Secondary outcomes included safety, secondary infection rate, duration of oxygen therapy dependency, acute kidney injury and need for intensive care. Patients were followed up for 28 days after admission. We enrolled 188 patients; 98 were assigned to the propolis group and 90 to the placebo group. The post-intervention length of hospital stay was of 6.5 ± 6.0 days in the propolis group versus 7.7 ± 7.1 days in the control group (95% CI - 0.74 [- 1.94 to 0.42]; p = 0.22). Propolis did not have significant impact on the need for oxygen supplementation or frequency of AKI. There was a significant difference in the incidence of secondary infection between groups, with 6.1% in the propolis group versus 18.9% in the control group (95% CI - 0.28 [0.1-0.76], p = 0.01). The use of EPP-AF was considered safe and associated with a decrease in secondary infections. The drug was not associated with a significant reduction in length of hospital stay. ClinicalTrials.gov (NCT04800224).

Perfil epidemiológico de pacientes com degeneração macular relacionada à idade / Epidemiological profile of patients with age-related macular degeneration

RESUMO Objetivo Demonstrar o perfil epidemiológico e fatores de riscos de pacientes com degeneração macular relacionada à idade. Métodos Estudo observacional e seccional. Foi incluído um olho de cada paciente com maior comprometimento visual por degeneração macular relacionada à idade atendido no Hospital Universitário Antônio Pedro. A variável principal a ser comparada foi a presença de degeneração macular relacionada à idade dividida nos estágios inexpressivo, inicial, intermediário e avançado, segundo classificação do estudo AREDS. As variáveis secundárias foram os dados demográficos (sexo, idade, raça, faixa etária), índice de massa corporal, cor da íris, história familiar de degeneração macular relacionada à idade, status do cristalino, longo tempo exposição à luz ultravioleta e tabagismo. Foram realizados testes estatísticos com análise de Kruskal-Wallis, do teste do qui-quadrado e teste t de Student. O nível de significância foi definido em 5%. Resultados Após os critérios de inclusão e exclusão, 126 pacientes foram incluídos neste estudo, sendo 20 pacientes com degeneração macular relacionada à idade inexpressiva, 30 pacientes com degeneração macular relacionada à idade inicial, 30 pacientes com degeneração macular relacionada à idade intermediária e 46 pacientes com degeneração macular relacionada à idade avançada. Dentre todos os fatores de risco pesquisados, apenas o tabagismo se mostrou estatisticamente significativo (p=0,03). Conclusão O tabagismo como fator de risco para degeneração macular relacionada à idade apresentou ter importância expressiva prevalente nesta pesquisa e até mesmo como fator preventivo dessa morbidade ocular.

ABSTRACT Purpose To demonstrate the epidemiological profile and risk factors of patients with age-related macular degeneration (ARMD). Methods Observational and sectional study. One eye of each patient with greater visual impairment due to AMD treated at the University Hospital Antônio Pedro was included. The main variable to be compared was the presence of AMD divided into inexpressive, initial, intermediate, and advanced stages, according to the classification of the AREDS study. The secondary variables were demographics (gender, age, race, age group), body mass index, iris color, family history of ARMD, lens status, long-term exposure to ultraviolet light and smoking. Statistical tests were performed with Kruskal-Wallis and Chi-square analyses and Student's t test. The significance level was set at 5%. Results After the inclusion and exclusion criteria, 126 patients were included in this study, 20 patients with non-expressive AMD, 30 patients with early AMD, 30 patients with intermediate AMD, and 46 patients with advanced AMD. Among all the risk factors surveyed, only smoking was statistically significant (p = 0.03). Conclusion Smoking as a risk factor for AMD had significant relevance prevalent in this research and even as a preventive factor for this ocular morbidity.

Calibration and validation of the Pneumonia Shock Score in critically ill patients with SARS-CoV-2 infection, a multicenter prospective cohort study.

Background: Prognostic tools developed to stratify critically ill patients in Intensive Care Units (ICUs), are critical to predict those with higher risk of mortality in the first hours of admission. This study aims to evaluate the performance of the pShock score in critically ill patients admitted to the ICU with SARS-CoV-2 infection. Methods: Prospective observational analytical cohort study conducted between January 2020 and March 2021 in four general ICUs in Salvador, Brazil. Descriptive statistics were used to characterize the cohort and a logistic regression, followed by cross-validation, were performed to calibrate the score. A ROC curve analysis was used to assess accuracy of the models analyzed. Results: Six hundred five adult ICU patients were included in the study. The median age was 63 (IQR: 49-74) years with a mortality rate of 33.2% (201 patients). The calibrated pShock-CoV score performed well in prediction of ICU mortality (AUC of 0.80 [95% Confidence Interval (CI): 0.77-0.83; p-value < 0.0001]). Conclusions: The pShock-CoV score demonstrated robust discriminatory capacity and may assist in targeting scarce ICU resources during the COVID-19 pandemic to those critically ill patients most likely to benefit.

Prediabetes Induces More Severe Acute COVID-19 Associated With IL-6 Production Without Worsening Long-Term Symptoms.

Aims: Pre-existing conditions, such as age, hypertension, obesity, and diabetes, constitute known risk factors for severe COVID-19. However, the impact of prediabetes mellitus (PDM) on COVID-19 severity is less clear. This study aimed to evaluate the influence of PDM in the acute and long-term phases of COVID-19. Materials and methods: We compared inflammatory mediators, laboratory and clinical parameters and symptoms in COVID-19 patients with prediabetes (PDM) and without diabetes (NDM) during the acute phase of infection and at three months post-hospitalization. Results: Patients with PDM had longer hospital stays and required intensive care unit admission more frequently than NDM. Upon hospitalization, PDM patients exhibited higher serum levels of interleukin 6 (IL-6), which is related to reduced partial pressure of oxygen (PaO2) in arterial blood, oxygen saturation (SpO2) and increased COVID-19 severity. However, at three months after discharge, those with PDM did not exhibit significant alterations in laboratory parameters or residual symptoms; however, PDM was observed to influence the profile of reported symptoms. Conclusions: PDM seems to be associated with increased risk of severe COVID-19, as well as higher serum levels of IL-6, which may constitute a potential biomarker of severe COVID-19 risk in affected patients. Furthermore, while PDM correlated with more severe acute-phase COVID-19, no long-term worsening of sequelae was observed.

Cerebral Autoregulation Indices Are Not Interchangeable in Patients With Sepsis.

Introduction: Dynamic cerebral autoregulation (dCA) is frequently altered in patients with sepsis and may be associated with sepsis-associated brain dysfunction. However, the optimal index to quantify dCA in patients with sepsis is currently unknown. Objective: To assess the agreement between two validated dCA indices in patients with sepsis. Methods: Retrospective analysis of prospectively collected data in patients with sepsis; those with acute or chronic intracranial disease, arrhythmias, mechanical cardiac support, or history of supra-aortic vascular disease were excluded. Transcranial Doppler was performed on the right or left middle cerebral artery (MCA) with a 2-MHz probe, and MCA blood flow velocity (FV) and arterial pressure (BP) signals were simultaneously recorded. We calculated two indices of dCA: the mean flow index (Mxa), which is the Pearson correlation coefficient between BP and FV (MATLAB, MathWorks), and the autoregulation index (ARI), which is the transfer function analysis of spontaneous fluctuations in BP and FV (custom-written FORTRAN code). Impaired dCA was defined as Mxa >0.3 or ARI ≤ 4. The agreement between the two indices was assessed by Cohen's kappa coefficient. Results: We included 95 patients (age 64 ± 13 years old; male 74%); ARI was 4.38 [2.83-6.04] and Mxa was 0.32 [0.14-0.59], respectively. There was no correlation between ARI and Mxa (r = -0.08; p = 0.39). dCA was altered in 40 (42%) patients according to ARI and in 50 (53%) patients according to Mxa. ARI and Mxa were concordant in classifying 23 (24%) patients as having impaired dCA and 28 (29%) patients as having intact dCA. Cohen's kappa coefficient was 0.08, suggesting poor agreement. ARI was altered more frequently in patients on mechanical ventilation than others (27/52, 52% vs. 13/43, 30%, p = 0.04), whereas Mxa did not differ between those two groups. On the contrary, Mxa was altered more frequently in patients receiving sedatives than others (23/34, 68% vs. 27/61, 44%, p = 0.03), whereas ARI did not differ between these two groups. Conclusions: Agreement between ARI and Mxa in assessing dCA in patients with sepsis was poor. The identification of specific factors influencing the dCA analysis might lead to a better selection of the adequate cerebral autoregulation (CAR) index in critically ill patients with sepsis.

POCUS, how can we include the brain? An overview.

Point-of-care ultrasound (POCUS) is an essential tool to assess and manage different pathologies in the intensive care unit, and many protocols have been proposed for its application in critical care literature. However, the brain has been overlooked in these protocols.Brain ultrasonography (BU) is easily available, and it allows a goal-directed approach thanks to its repeatability and immediate interpretation and provides a quick management and real time assessment of patients' conditions. Based on recent studies, the increasing interest from intensivists, and the undeniable benefits of ultrasound, the main goal of this overview is to describe the main evidence and progresses in the incorporation of BU into the POCUS approach in the daily practice, and thus becoming POCUS-BU. This integration would allow a noninvasive global assessment to entail an integrated analysis of the critical care patients.

Prediction of hemodynamic tolerance of intermittent hemodialysis in critically ill patients: a cohort study.

The evaluation and management of fluid balance are key challenges when caring for critically ill patients requiring renal replacement therapy. The aim of this study was to assess the ability of clinical judgment and other variables to predict the occurrence of hypotension during intermittent hemodialysis (IHD) in critically ill patients. This was a prospective, observational, single-center study involving critically ill patients undergoing IHD. The clinical judgment of hypervolemia was determined by the managing nephrologists and critical care physicians in charge of the patients on the basis of the clinical data used to calculate the ultrafiltration volume and rate for each dialysis treatment. Seventy-nine (31.9%) patients presented with hypotension during IHD. Patients were perceived as being hypervolemic in 109 (43.9%) of the cases by nephrologists and in 107 (43.1%) by intensivists. The agreement between nephrologists and intensivists was weak (kappa = 0.561). Receiver operating characteristic curve analysis yielded an AUC of 0.81 (95% CI 0.75 to 0.84; P < 0.0001), and a cutoff value of 70 mm for the vascular pedicle width (VPW) had the highest accuracy for the prediction of the absence of hypotension. The clinical judgment of hypervolemia did not predict hypotension during IHD. The high predictive ability of the VPW may assist clinicians with critical thinking.

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.

LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes.

Diabetes is a known risk factor for severe coronavirus disease 2019 (COVID-19), the disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is a lack of knowledge about the mechanisms involved in the evolution of COVID-19 in individuals with diabetes. We aimed to evaluate whether the chronic low-grade inflammation of diabetes could play a role in the development of severe COVID-19. We collected clinical data and blood samples of patients with and without diabetes hospitalized for COVID-19. Plasma samples were used to measure inflammatory mediators and peripheral blood mononuclear cells, for gene expression analysis of the SARS-CoV-2 main receptor system (ACE2/TMPRSS2), and for the main molecule of the leukotriene B4 (LTB4) pathway (ALOX5). We found that diabetes activates the LTB4 pathway and that during COVID-19 it increases ACE2/TMPRSS2 as well as ALOX5 expression. Diabetes was also associated with COVID-19-related disorders, such as reduced oxygen saturation as measured by pulse oximetry/fraction of inspired oxygen (FiO2) and arterial partial pressure of oxygen/FiO2 levels, and increased disease duration. In addition, the expressions of ACE2 and ALOX5 are positively correlated, with increased expression in patients with diabetes and COVID-19 requiring intensive care assistance. We confirmed these molecular results at the protein level, where plasma LTB4 is significantly increased in individuals with diabetes. In addition, IL-6 serum levels are increased only in individuals with diabetes requiring intensive care assistance. Together, these results indicate that LTB4 and IL-6 systemic levels, as well as ACE2/ALOX5 blood expression, could be early markers of severe COVID-19 in individuals with diabetes.

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.

Differential impact of on-site or telepharmacy in the intensive care unit: a controlled before-after study.

BACKGROUND: Clinical pharmacists have an important role in the intensive care unit (ICU) team but are scarce resources. Our aim was to evaluate the impact of on-site pharmacists on medical prescriptions in the ICU. METHODS: This is a retrospective, quasi-experimental, controlled before-after study in two ICUs. Interventions by pharmacists were evaluated in phase 1 (February to November 2016) and phase 2 (February to May 2017) in ICU A (intervention) and ICU B (control). In phase 1, both ICUs had a telepharmacy service in which medical prescriptions were evaluated and interventions were made remotely. In phase 2, an on-site pharmacist was implemented in ICU A, but not in ICU B. We compared the number of interventions that were accepted in phase 1 versus phase 2. RESULTS: During the study period, 8797/9603 (91.6%) prescriptions were evaluated, and 935 (10.6%) needed intervention. In phase 2, there was an increase in the proportion of interventions that were accepted by the physician in comparison to phase 1 (93.9% versus 76.8%, P < 0.001) in ICU A, but there was no change in ICU B (75.2% versus 73.9%, P = 0.845). CONCLUSION: An on-site pharmacist in the ICU was associated with an increase in the proportion of interventions that were accepted by physicians.

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.

Ten Good Reasons to Practice Neuroultrasound in Critical Care Setting.

In the beginning, cerebral ultrasound (US) was not considered feasible because the intact skull was a seemingly impenetrable obstacle. For this reason, obtaining a clear image resolution had been a challenge since the first use of neuroultrasound (NUS) for the assessment of small deep brain structures. However, the improvements in transducer technologies and advances in signal processing have refined the image resolution, and the role of NUS has evolved as an imaging modality for the brain parenchyma within multiple pathologies. This article summarizes ten crucial applications of cerebral ultrasonography for the evaluation and management of neurocritical patients, whose transfer from and to intensive care units poses a real problem to medical care staff. This also encompasses ease of use, low cost, wide acceptance by patients, no radiation risk, and relative independence from movement artifacts. Bedsides, availability and reliability raised the interest of critical care intensivists in using it with increasing frequency. In this mini-review, the usefulness and the advantages of US in the neurocritical care setting are discussed regarding ten aspects to encourage the intensivist physician to practice this important tool.

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.